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  • 1.
    Abdiu, Avni
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Larsson, Sven-Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Wasteson, Åke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Walz, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Suramin blocks growth-stimulatory effects of platelet-derived growth factor on malignant fibrous histiocytomas in vitro.1999In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 146, p. 189-194Article in journal (Refereed)
  • 2.
    Abdiu, Avni
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Nakamura, Hajime
    Sahaf, Bita
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Yodoi, Junji
    Holmgren, Arne
    Rosén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Thioredoxin blood level increases after severe burn injury2000In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 2, no 4, p. 707-716Article in journal (Refereed)
    Abstract [en]

    We have investigated the thioredoxin (TRX) levels in severely burned patients and the possible origin of TRX, based on the recent understanding that TRX is a potent antioxidant with cytoprotective functions. Serum and plasma samples from burns patients and healthy blood donors were collected during the first 10 post-bum days and analyzed in a sandwich TRX enzyme-linked immunosorbent assay (ELISA). The TRX levels found were correlated to a panel of blood tests. The presence of TRX in platelets was investigated by immunoelectron microscopy and Western blotting. TRX serum levels of the severely burned patients showed a significant increase, with a mean serum TRX concentration on the day of injury of 76.5 ▒ 19.5 ng/ml (mean ▒ SD) and on post-burn day one 122.6 ▒ 66.9 ng/ml, compared to control blood donor levels of 22.7 ▒ 12.2 ng/ml (p = 0.0041 and 0.0117, respectively). A second peak of increase was found on post-burn days 7 to 9 with a four- to five-fold rise in concentration compared to controls. TRX elevation correlated well with increased platelet (p = 0.007) and leukocyte counts (p = 0.002). We also demonstrated by immunoelectron microscopy and Western blotting the presence of TRX in platelets. In conclusion, our demonstration of TRX release in burn injuries indicates that the TRX system is involved in a rapid antioxidant defense, coagulation processes, cell growth, and control of the extracellular peroxide tone intimately linked to cytoprotection and wound healing in burns. One of the cell types that delivers TRX promptly and efficiently into the blood may be the platelet.

  • 3.
    Abdiu, Avni
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Wingren, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Larsson, S-E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Wasteson, Åke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Walz, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Effects of human platelet-derived growth factor-AB on sarcoma growth in vitro and in vivo.1999In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 141, p. 39-45Article in journal (Refereed)
  • 4. Adage, Tiziana
    et al.
    Scheurink, Anton
    de Boer, Sietse
    de Vries, Koert
    Konsman, Jan Pieter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Kuipers, Folkert
    Adan, Roger
    Baskin, Denis
    Schwartz, Michael
    van Dijk, Gertjan
    Hypothalamic, metabolic,and behavioral responses to pharmacological inhibition of CNS melanocortin signaling in rats.2001In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 21, p. 3639-3645Article in journal (Refereed)
  • 5.
    Adell, Gunnar C. E.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Evertsson, Sofia
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Apoptosis in rectal carcinoma: Prognosis and recurrence after preoperative radiotherapy2001In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 91, no 10, p. 1870-1875Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Rectal carcinoma is common, with considerable local recurrence and death rates. Preoperative radiotherapy and refined surgical techniques can improve local control. The aim of this study was to investigate the interaction between apoptosis and the outcome of rectal carcinoma, with and without short-term preoperative radiotherapy.

    METHODS: Specimens were from 162 patients from the Southeast Swedish Health Care region included in the Swedish Rectal Cancer Trial between 1987-1990. New sections from the paraffin blocks of the preoperative biopsies and the surgical specimens were examined for apoptosis using the terminal deoxynucleotidyl transferase mediated digoxigenin nick end labeling (TUNEL) method.

    RESULTS: The mean percentage of apoptotic cells was 0.3% (0-4%) and 1.1% (0-14.5%) for the preoperative biopsy and the surgical specimen, respectively. The authors analyzed the surgical specimens from nonirradiated patients and divided them into three groups by apoptotic index (AI) as follows: 0%, 0-1%, and > 1%. A high AI was associated with a decreased local recurrence rate compared with an intermediate or a low AI (P = 0.024). There was no significant relation between AI and survival. There was a significant reduction in the local recurrence rate for irradiated patients compared with the nonirradiated in the low (P = 0.015) and intermediate (P = 0.038) AI groups. In the high AI group, there were few recurrences and no significant difference was observed between irradiated and nonirradiated patients. The relative risk of death from rectal carcinoma in Dukes A-C patients was not significantly decreased by radiotherapy, but, in the intermediate AI group, there was a trend (P = 0.08) in favor of the irradiated patients.

    CONCLUSION: A high AI in rectal carcinoma indicated a decreased local recurrence rate.

  • 6.
    Adell, Gunnar
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Jansson, Agneta
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer2001In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 50, no 3, p. 659-663Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival.

    PURPOSE: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy.Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen.

    MATERIALS: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990.

    RESULTS: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p = 0.03), with a trend toward improved disease-free survival (p = 0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates.

    CONCLUSION: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer.

  • 7.
    Adolfsson, Per
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Haug, Ingrid
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Svensson, Samuel
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas2000In: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 6, no 9, p. 835-842Article in journal (Refereed)
    Abstract [en]

    Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α2- and β2-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α22-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β2-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β2-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.

  • 8.
    Ahmadi, Ahmad
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Genetic predisposition and risk factors for neurodegenerative diseases2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The inter-individual variability in biotransformation, may lead to differences in activation and detoxification of both endogenous and exogenous compounds. Polymorphism studies in such genes were applied for Parkinson's disease (PD) and Chronic toxic encephalopathy (CTE), two diseases influenced by both genetic and enviromnental factors.

    An elevated median age for the onset of PD was found among GS1M1 gene carriers compared to PD patients being GS1M1 null genotypes (68 years versus 57 years). No similar difference was found for GSTT1. mEPHX (113HH) isoform, which has been suggested as a low activity variant, is over represented in PD patients (OR=3.8, CI 95%, 1.2-11.8).

    Monoamine oxidases (MAO-A and -B) are important in the dopamine metabolism and in the detoxification of neurotoxins and genetic variants in these genes have earlier been assigned to PD. However, no difference was revealed between any of the polymorphisms studied in the MAO-A and -B genes and PD. Smoking displayed an enviromnental exposure with a strong decreased risk for PD in this study (OR=0.40 for men and OR=0.48 for women) but no obvious interaction with the MAO genotypes could be observed.

    Mitochondrial dysfunction and oxidative stress have been hypothesized to contribute to the pathogenesis of PD. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals in mitochondria. Polymorphisms neither in superoxide dismutase 2 (SOD2) nor mitochondrial complex I subunit, NDUFV2, were associated with PD.

    An increased risk ratio for CTE was found in smokers with the GSTM1 null genotype (RR=2.5, Cl 95%, 1.4-4.2) or the GSTT1 null genotype (RR=1.4, Ci 95%, 1.02-2.0). In non-smokers GS1M1 null genotype did not confer any risk for CTE. Polymorphisms in mEPHX were not associated with an increased risk for CTE.

    Thus, various genetic and enviromnental factors most likely influence both PD and solvent-induced CTE. Detoxification pathways may represent important protective mechanisms against reactive intermediates, thus genetic predisposition in these pathways could modify the susceptibility and onset of PD and solvent-induced CTE.

    List of papers
    1. GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset
    Open this publication in new window or tab >>GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset
    Show others...
    2000 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 269, no 3, p. 676-680Article in journal (Refereed) Published
    Abstract [en]

    Both environmental and genetic factors are involved in the development of PD and biotransformation of exogenous and endogenous compounds and may play a role in inter-individual susceptibility. Therefore, we investigated the presence of null genotypes of GSTM1, GSTT1, and two polymorphisms of mEPHX in subjects with Parkinson's disease and in a reference population. The study included 35 male PD patients and a male control group including 283 subjects. Homozygosity of the histidine (H) 113 isoform of mEPHX was significantly increased in PD patients (odds ratio = 3.8 CI 95% 1.2–11.8) and analysis of allele frequencies displayed an increased frequency of the H-allele among PD patients (odds ratio = 1.9 CI 95% 1.1–3.3). However, a significantly elevated median age for the onset of PD was found among GSTM1 gene carriers (median age = 68 years) compared to PD patients being GSTM1 null genotypes (median age = 57 years). Our observations suggest that (H) 113 isoform of mEPHX, which has been suggested as a low activity isoform, is overrepresented in PD patients and that inherited carriers of the GSTM1 gene postpone the onset of PD. These detoxification pathways may represent important protective mechanisms against reactive intermediates modifying the susceptibility and onset of PD.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24837 (URN)10.1006/bbrc.2000.2338 (DOI)9235 (Local ID)9235 (Archive number)9235 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Monoamine oxidase A and B genes polymorphisms in Parkinson's disease
    Open this publication in new window or tab >>Monoamine oxidase A and B genes polymorphisms in Parkinson's disease
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized by degeneration of nig:rostriatal dopaminergic neurons including the loss of cell bodies in the pars compacta of substantia nigra (SN). The mechanism for neurodegeneration is unknown, but the pathogenesis is considered to be multifactorial involving exposure for toxins, genetic inheritance, age, oxidative stress and mitochondrial electron transport chain defects. This study has been focused on polymorphisms in the genes for the enzymes monoamine oxidase A and B (MAO-A, MAO-B) and relation to smoking for the development of idiopathic Parkinson's disease. MAO enzymes are important in the dopamine metabolism and in the detoxification of neurotoxins. During metabolism of dopamine, MAO generates large amounts of free radicals and hydrogen peroxide, and may damage the neurons in substantia nigra, which has been suggested as a pathologic mechanism for PD.

    Blood samples were collected from 256 PD patients, age 30-80 years, and 582 unrelated control individuals, age 31 - 78 years, from southeastern Sweden.

    Two polymorphisms (exon 8 and exon 14) located in the MAO-A gene and one polymorphism located in the MA O-B gene were examined, with denatming HPLC, PCR-RFLP or DNA sequencing. Genotype and allele frequencies were determined for patients and controls. No statistical significant difference was revealed between any of the polymorphisms in the MAO-A and MAO-B genes and Parkinson's disease. Smoking displayed an enviromnental exposure with a strong decreased risk for both male (OR=0.40, 95% CI 0.25 - 0.63) and female (OR=0.48, 95% CI 0.25-0.89) PD without any interaction with MAO genotype.

    The polymorphisms in MAO genes might therefore not be acting as modifiers of risk for developing of PD either by itself or by interacting with smoking. With respect to the size of the study (256 PD patients and 582 controls) MAO polymorphisms do not represent any predisposing factor or a weak PD susceptibility factor.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84799 (URN)
    Available from: 2012-10-22 Created: 2012-10-22 Last updated: 2012-10-22Bibliographically approved
    3. Manganese superoxide dismutase and NDUFV2 polymorphisms and susceptibility to Parkinson's disease
    Open this publication in new window or tab >>Manganese superoxide dismutase and NDUFV2 polymorphisms and susceptibility to Parkinson's disease
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Mitochondrial dysfunction has been hypothesized to contribute to the pathogenesis of Parkinson's disease (PD). Oxidative stress and production of oxygen radicals is produced in mitochondria. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals. Oxidative stress has also an important role to decrease Complex I activity in the mitochondria. In addition, Complex I contains several subunits, where one, NDUFV2, plays a major role in the electron transport pathway of Complex I in substantia nigra.

    The aim of this project was to study polymorphisms in MTS-SOD2 and the Complex I subunit, NDUFV2 as predisposing factors for the development of idiopathic PD.

    Blood samples from 200 PD and 404 population controls were collected from the Southeastern part of Sweden. DNA was isolated and the polymorphisms were analyzed by pyrosequencing and direct dideoxy termination sequencing.

    Genotypes and allele frequencies were compared for the patient and control groups with Χ2 statistics. No statistical significant difference was evident for any of the polymorphisms neither in MTS-SOD2 (OR=0<85, 95% CI, 0<52-1.38) nor NDUFV2 (OR=0.64, 95% CI, 0.24-1.64) genes and PD.

    These results indicate that the MTS-SOD2 and NDUFV2 gene variants do not contribute to PD pathogenesis.

    Keywords
    SOD2, NDUFV2, polymorphisms, Parkinson's disease
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84800 (URN)
    Available from: 2012-10-22 Created: 2012-10-22 Last updated: 2012-10-22Bibliographically approved
    4. Glutathione S-transferase M1 null genotype as a risk modifier for solvent-induced chronic toxic encephalopathy
    Open this publication in new window or tab >>Glutathione S-transferase M1 null genotype as a risk modifier for solvent-induced chronic toxic encephalopathy
    Show others...
    1996 (English)In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 22, no 5, p. 360-363Article in journal (Refereed) Published
    Abstract [en]

    Objectives Exposure to organic solvents increases the risk of neuropsychiatric disability or chronic toxic encephalopathy (CTE). Polymorphisms in the biotransformation of xenobiotics and solvents may influence individual susceptibility to develop toxic effects. In this study the problem of whether there could be any association between the glutathione S-transferase M1 (GSTM1) null genotype and the risk for CTE, with regard to solvent exposure, was investigated.

    Methods Sixty patients referred to a clinic because of some degree of some degrees of psychiatric or neurological symptoms, as well as exposure to solvents, were examined by means of a validated questionnaire and psychometric testing. The degree of exposure to solvents was assessed by a thorough interview. According to clinical findings, the patients were classified into three categories as those with solvent-induced CTE, those with incipient CTE, and those who were non-CTE patients. Afterwards, leukocyte DNA (deoxyribonucleic acid) was isolated and the GSTM1 null genotype was determined by an assay based on polymerase chain reaction, blindly with regard to both exposure and disease status.

    Results The relative proportion (RP) of GSTM1 null genotypes was significantly increased for patients with a diagnosed CTE when they were compared with non-CTE patients (RP 2.55, 95% confidence interval 1.0--6.2). Dichotomizing the patients by high and low exposure revealed an increased risk for both GSTM1 gene carriers and the GSTM1 null genotype in the high-exposure group, the relative risks (RR) being 4.5 and 7.9, respectively. The chi-square for the Mantel extension for trend was 6.2 (P=0.025).

    Conclusion The GSTM1 null genotype acts as a risk modifier for CTE among patients occupationally exposed to solvents. The risk seems to increase in a dose-dependent fashion.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84801 (URN)10.5271/sjweh.154 (DOI)
    Available from: 2012-10-22 Created: 2012-10-22 Last updated: 2017-12-07Bibliographically approved
    5. Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy
    Open this publication in new window or tab >>Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy
    2002 (English)In: Toxicology and industrial health, ISSN 0748-2337, E-ISSN 1477-0393, Vol. 18, no 6, p. 289-296Article in journal (Refereed) Published
    Abstract [en]

    Exposure to organic solvents is still common in industrial and other work environments, and increases the risk of chronic toxic encephalopathy (CTE). Genetic variation in metabolic enzymes for solvents and other xenobiotics may modify the risk of developing toxic effects. Therefore, we investigated the presence of null genotypes for glutathione S-transferases M1 and T1 (GSTM1, GSTT1) and two genetic polymorphisms of microsomal epoxide hydrolase (mEPHX) in relation to the risk for chronic toxic encephalopathy (CTE) when exposed to solvents and smoking. We genotyped 115 patients who were classified into three categories: CTE (n = 56), incipient CTE (n = 27) and non-CTE (n = 32) patients. DNA was isolated from leucocytes and the GSTM 1 and GSTT1 null genotypes were determined by multiplex-polymerase chain reaction. The two polymorphisms of mEPHX were analysed by PCR-RFLP (restriction fragment length polymorphism) based assays. All analyses were performed blindly with regard to both exposure and disease status. An increased binomial regression risk ratio = 2.5, 95% confidence interval (CI) 1.5-4.2, of the GSTM1 null genotype for CTE was found in smokers and for the GSTT1 null genotype (binomial regression risk ratio 1.5, 95% CI 1.0-2.0). In nonsmokers, the GSTM1 null genotype did not confer any risk for CTE. None of the studied mEPHX polymorphisms were associated with an increased risk for CTE. We suggest that the GSTM1 null genotype in smokers is a possible risk for solvent-induced CTE.

    Keywords
    chronic toxic encephalopathy, molecular epidemiology, polymorphism, smoking, solvent exposure
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-46280 (URN)10.1191/0748233702th152oa (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
  • 9.
    Ahmadi, Ahmad
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bivik, Cecilia
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Monoamine oxidase A and B genes polymorphisms in Parkinson's diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized by degeneration of nig:rostriatal dopaminergic neurons including the loss of cell bodies in the pars compacta of substantia nigra (SN). The mechanism for neurodegeneration is unknown, but the pathogenesis is considered to be multifactorial involving exposure for toxins, genetic inheritance, age, oxidative stress and mitochondrial electron transport chain defects. This study has been focused on polymorphisms in the genes for the enzymes monoamine oxidase A and B (MAO-A, MAO-B) and relation to smoking for the development of idiopathic Parkinson's disease. MAO enzymes are important in the dopamine metabolism and in the detoxification of neurotoxins. During metabolism of dopamine, MAO generates large amounts of free radicals and hydrogen peroxide, and may damage the neurons in substantia nigra, which has been suggested as a pathologic mechanism for PD.

    Blood samples were collected from 256 PD patients, age 30-80 years, and 582 unrelated control individuals, age 31 - 78 years, from southeastern Sweden.

    Two polymorphisms (exon 8 and exon 14) located in the MAO-A gene and one polymorphism located in the MA O-B gene were examined, with denatming HPLC, PCR-RFLP or DNA sequencing. Genotype and allele frequencies were determined for patients and controls. No statistical significant difference was revealed between any of the polymorphisms in the MAO-A and MAO-B genes and Parkinson's disease. Smoking displayed an enviromnental exposure with a strong decreased risk for both male (OR=0.40, 95% CI 0.25 - 0.63) and female (OR=0.48, 95% CI 0.25-0.89) PD without any interaction with MAO genotype.

    The polymorphisms in MAO genes might therefore not be acting as modifiers of risk for developing of PD either by itself or by interacting with smoking. With respect to the size of the study (256 PD patients and 582 controls) MAO polymorphisms do not represent any predisposing factor or a weak PD susceptibility factor.

  • 10.
    Ahmadi, Ahmad
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Fredriksson, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Jerregård, H.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Åkerbäck, Anita
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Fall, Per-Arne
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Rannug, A.
    National Institute for Working Life, Solna and Inst. of Environ. Medicine, Karolinska Institutet, Stockholm, Sweden.
    Axelson, Olav
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset2000In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 269, no 3, p. 676-680Article in journal (Refereed)
    Abstract [en]

    Both environmental and genetic factors are involved in the development of PD and biotransformation of exogenous and endogenous compounds and may play a role in inter-individual susceptibility. Therefore, we investigated the presence of null genotypes of GSTM1, GSTT1, and two polymorphisms of mEPHX in subjects with Parkinson's disease and in a reference population. The study included 35 male PD patients and a male control group including 283 subjects. Homozygosity of the histidine (H) 113 isoform of mEPHX was significantly increased in PD patients (odds ratio = 3.8 CI 95% 1.2–11.8) and analysis of allele frequencies displayed an increased frequency of the H-allele among PD patients (odds ratio = 1.9 CI 95% 1.1–3.3). However, a significantly elevated median age for the onset of PD was found among GSTM1 gene carriers (median age = 68 years) compared to PD patients being GSTM1 null genotypes (median age = 57 years). Our observations suggest that (H) 113 isoform of mEPHX, which has been suggested as a low activity isoform, is overrepresented in PD patients and that inherited carriers of the GSTM1 gene postpone the onset of PD. These detoxification pathways may represent important protective mechanisms against reactive intermediates modifying the susceptibility and onset of PD.

  • 11.
    Ahmadi, Ahmad
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Johansson, Sofia
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Manganese superoxide dismutase and NDUFV2 polymorphisms and susceptibility to Parkinson's diseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Mitochondrial dysfunction has been hypothesized to contribute to the pathogenesis of Parkinson's disease (PD). Oxidative stress and production of oxygen radicals is produced in mitochondria. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals. Oxidative stress has also an important role to decrease Complex I activity in the mitochondria. In addition, Complex I contains several subunits, where one, NDUFV2, plays a major role in the electron transport pathway of Complex I in substantia nigra.

    The aim of this project was to study polymorphisms in MTS-SOD2 and the Complex I subunit, NDUFV2 as predisposing factors for the development of idiopathic PD.

    Blood samples from 200 PD and 404 population controls were collected from the Southeastern part of Sweden. DNA was isolated and the polymorphisms were analyzed by pyrosequencing and direct dideoxy termination sequencing.

    Genotypes and allele frequencies were compared for the patient and control groups with Χ2 statistics. No statistical significant difference was evident for any of the polymorphisms neither in MTS-SOD2 (OR=0<85, 95% CI, 0<52-1.38) nor NDUFV2 (OR=0.64, 95% CI, 0.24-1.64) genes and PD.

    These results indicate that the MTS-SOD2 and NDUFV2 gene variants do not contribute to PD pathogenesis.

  • 12. Alvarsson, M
    et al.
    Sundkvist, G
    Lager, I
    Henricsson, M
    Berntorp, K
    Fernqvist-Forbes, E
    Steen, L
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Westermark, P
    Orn, T
    Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 8, p. 2231-2237Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment. RESEARCH DESIGN AND METHODS - ▀-Cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0-2 years before inclusion in a Swedish multicenter randomized clinical trial. Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5-10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2-3 days of temporary withdrawal of treatment. RESULTS - After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 ▒ 0.08 nmol/l, whereas it was decreased by 0.12 ▒ 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups. After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA1c levels decreased significantly during the first year in both groups, however, at the end of the second year, HbA1c had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA1c during the second year was significant between groups, P < 0.02 A questionnaire indicated no difference in well-being related to treatment. CONCLUSIONS - Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.

  • 13.
    Amandusson, Åsa
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Östrogenreceptorer kan reglera känsligheten för smärta. Möjlig förklaring till vissa kroniska smärttillstånd.2001In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, p. 1774-1778Article in journal (Other academic)
  • 14.
    Anderson, Emma
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bjartmar, Carl
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Oligodendrocytens nyckelroll2000In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, p. 3265-3268Article in journal (Other (popular science, discussion, etc.))
  • 15.
    Anderson, Emma S.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Morphology of early developing oligodendrocytes in the ventrolateral chicken spinal cordManuscript (preprint) (Other academic)
    Abstract [en]

    As observed by Del Rio-Hortega (1928), the oligodendroglial population includes Type I and 11 cells related to several thin axons, Type III cells with a few processes in relation to relatively thick axons and Type IV cells related to a single thick axon. This structural diversity of oligodendrocytes is accompanied by a molecular heterogeneity. In the chicken spinal cord oligodendrocytes have begun to contact axons at embryonic day (E)10 and compact sheaths have appeared by E12. AI the latter stage, most sheath-forming oligodendrocytes contact more than one axon. At E15, however, each sheath-forming cell seems to have developed a Schwann cell-like anatomy, being related to a single axon. Against this background, the present study examines the 3D anatomy of early developing oligodendrocytes in the chicken spinal cord. Examination of slices immunostained with antibodies against the oligodendroglial marker 04 showed that a few positive cells are at hand at E6, after which the occurrence increases with age. At E12 most immunostained cells have two or more processes. At E15 however, dye-injected oligodendrocytes have developed a Type IV structure. Between E12 and E15, mean sheath length increases some 4x, from 50 µm to over 200 flm, while the length of the spinal cord increases 36% only. Hence, early oligodendrocytes in chicken white matter develop a Type IV anatomy between E12 and E15 through an elimination of sheaths.

  • 16.
    Anderson, Emma S.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Morphology of early developing oligodendrocytes in the ventrolateral spinal cord of the chicken2003In: Journal of Neurocytology, ISSN 0300-4864, E-ISSN 1573-7381, Vol. 32, no 9, p. 1045-1053Article in journal (Refereed)
    Abstract [en]

    The oligodendroglial population includes Type I and II cells related to several thin axons, Type III cells with a few processes in relation to relatively thick axons and Type IV cells related to a single thick axon. This structural diversity of oligodendrocytes is accompanied by a molecular heterogeneity. In the chicken spinal cord, oligodendrocytes have begun to contact axons at embryonic day (E)10 and compact sheaths have appeared by E12. At the latter stage, most sheath-forming oligodendrocytes contact more than one axon. At E15, however, each sheath-forming cell seems to have developed a Schwann cell-like anatomy, being related to a single axon. Based on these findings, the present study examines more thoroughly the anatomy of early developing oligodendrocytes in the chicken spinal cord. Examination of slices immunostained with antibodies against the oligodendroglial marker O4 showed that a few positive cells are present at E6, after which the occurrence increases with age. At E12 most immunostained cells have two or more processes. At E15 however, dye-injected oligodendrocytes have developed a Type IV structure. Between E12 and E15, mean sheath length increases about 4×, from 50 µm to over 200 µm, while the length of the spinal cord increases 36% only. This indicates that early oligodendrocytes in chicken white matter develop a Type IV anatomy between E12 and E15 through an elimination of sheaths.

  • 17.
    Anderson, Emma S.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    The type IV Oligodendrocyte: experimental studies on chicken white matter2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In mammals, islet amyloid polypeptide (IAPP) is co-produced with insulin in pancreatic ß-cells. In the chicken, the expression of IAPP in the brain is more than 10-fold higher than in the pancreas. We made the fortuitous finding that a polyclonal rabbit antiserum raised against chicken IAPP did not recognise the immunogen, but labelled a subpopulation of oligodendroglia! cells in chicken white matter. The hitherto unknown antigen was called T4-O (Type 4 Oligodendrocyte) since it was localised to the Schwann cell-like Type IV oligodendrocyte of Del Rio-Hortega (1928). This formed a starting point for the present thesis, which is centred on the Type IV oligodendrocyte in chicken white matter.

    Biochemical analysis of chicken spinal cord showed that the T4-O molecule is a protein with a molecular weight of approximately 100 kDa and an isoelectric point of about 4. Further characterisation has not yet been possible.

    Immunohistochemical studies on frozen sections revealed that the white matter oligodendrocytes exhibit subpopulations expressing T4-O immunoreactivity strongly, weakly or not at all. Strongly T4-O immunoreactive (IR) oligodendrocytes are co-localised with thick myelinated fibres in the ventral (VF) and lateral funiculi of the spinal cord. A corresponding T4-O immunoreactivity is not found in the fish, the frog, the turtle, the rat and the rabbit.

    To find out when the T4-0 antigen first appears during development we examined sections from embryonic and post-hatching chicken spinal cords by immunohistochemistry. This showed that the T4-O molecule is first expressed in the VF at embryonic day (E)15, after which the number of IR cells increases with age. Oligodendrocytes cultivated in vitro without or with neurons do not develop a T4-O IR phenotype.

    These findings called for a closer analysis of the structural development of chicken VF white matter. Electron microscopic (EM) examination revealed a developmental sequence of events principally similar to the development of mammalian white matter, but with a more rapid time course. As seen in the electron microscope the first compact myelin has appeared by E12, when most oligodendrocytes are multipolar. By E15 it seems that these cells have developed a Type IV phenotype, possibly by eliminating some sheaths.

    Histochemical analysis of Vibratome sections showed that Marchi-positive myelinoid bodies are enriched in white matter areas containing many T4-O IR oligodendrocytes and many large myelinated axons.

    Examination of the three-dimensional (3D) anatomy of early VF oligodendrocytes in Vibratome slices after 04 labelling or after intracellular injection of a fluorescent dye revealed that these units indeed are Schwann cell-like, with a start length of around 50 µm. We also found that these sheaths expand very rapidly, reaching lengths exceeding 200 µm in three days (E12- E15). The 3D data conformed to our EM evidence that the early oligodendrocytes develop a unipolar Schwann cell-like Type IV anatomy through elimination of some sheaths.

    To my knowledge the present observations represent the first evidence for an oligodendroglia! heterogeneity in the chicken spinal cord. Differences among oligodendrocytes might, conceivably, explain why inherited disorders of myelin metabolism such as Krabbe's disease, affect some CNS areas more than others.

    List of papers
    1. Molecular heterogeneity of oligodendrocytes in chicken white matter
    Open this publication in new window or tab >>Molecular heterogeneity of oligodendrocytes in chicken white matter
    1999 (English)In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 27, no 1, p. 15-21Article in journal (Refereed) Published
    Abstract [en]

    The classical studies by Del Rio Hortega (Mem. Real. Soc. Espan. Hist. Nat. 14:40–122, 1928) suggest that the oligodendrocyte population includes four morphological subtypes. Recent data from the cat and the rat show that the anatomy of oligodendrocytes related to early myelinating prospective large fibers differs from that of oligodendrocytes related to late myelinating prospective small fibers. After application of a polyclonal antiserum to cryostat sections from the chicken CNS, we noted that glial cells in the spinal cord white matter had become labeled. Analysis of the occurrence and cellular localization of this immunoreactivity—the T4-O immunoreactivity—in the CNS of the adult chicken showed that T4-O immunoreactive cells are enriched in the ventral funiculus and superficially in the lateral funiculus of the spinal cord, where they are co-localized with large fibers. Double staining with T4-O antiserum and anti-GFAP or the lectin BSI-B4 revealed that T4-O immunoreactive cells are not astrocytes or microglia. Staining with anti-HSP108, a general marker for avian oligodendrocytes, showed that T4-O immunoreactivity defines an oligodendroglial subpopulation. A search for T4-O immunoreactivity in spinal cord white matter of some other vertebrates revealed that T4-O immunoreactive cells are not present in sections from fish, frog, turtle, rat, and rabbit spinal cord white matter. These results suggest the presence of a fiber size-related molecular heterogeneity among chicken white matter oligodendrocytes.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24854 (URN)10.1002/(SICI)1098-1136(199907)27:1<15::AID-GLIA2>3.0.CO;2-I (DOI)9254 (Local ID)9254 (Archive number)9254 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Developing chicken oligodendrocytes express the type IV oligodendrocyte marker T4-O in situ, but not in vitro
    Open this publication in new window or tab >>Developing chicken oligodendrocytes express the type IV oligodendrocyte marker T4-O in situ, but not in vitro
    Show others...
    2000 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 284, no 1-2, p. 21-24Article in journal (Refereed) Published
    Abstract [en]

    Accumulating data suggest that the oligodendrocyte population includes morphological and biochemical subtypes. We recently reported that a polyclonal antiserum against an unknown antigen, the T4-O molecule, labels a subpopulation of chicken oligodendrocytes, obviously representing the type IV variety of Del Rio Hortega. The present study examines the developmental expression of the T4-O molecule in situ and in vitro. The results show that T4-O immunoreactive cells first appear at E15 in the ventral funiculus. But, oligodendrocytes cultured in vitro with or without neurones do not develop a T4-O immunoreactivity. We conclude that oligodendrocytes in the spinal cord of chicken embryos first express the T4-O molecule some time after onset of myelination, and that the T4-O immunoreactive phenotype does not develop in vitro.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24853 (URN)10.1016/S0304-3940(00)00989-7 (DOI)9253 (Local ID)9253 (Archive number)9253 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Myelination of prospective large fibres in chicken ventral funiculus
    Open this publication in new window or tab >>Myelination of prospective large fibres in chicken ventral funiculus
    2000 (English)In: Journal of Neurocytology, ISSN 0300-4864, E-ISSN 1573-7381, Vol. 29, no 10, p. 755-764Article in journal (Refereed) Published
    Abstract [en]

    In mammals, the oligodendrocyte population includes morphological and molecular varieties. We reported previously that an antiserum against the T4-O molecule labels a subgroup of oligodendrocytes related to large myelinated axons in adult chicken white matter. We also reported that T4-O immunoreactive cells first appear in the developing ventral funiculus (VF) at embryonic day (E)15, subsequently increasing rapidly in number. Relevant fine structural data for comparison are not available in the literature. This prompted the present morphological analysis of developing and mature VF white matter in the chicken. The first axon-oligodendrocyte connections were seen at E10 and formation of compact myelin had started at E12. Between E12 and E15 the first myelinating oligodendrocytes attained a Schwann cell-like morphology. At hatching (E21) 60% of all VF axons were myelinated and in the adult this proportion had increased to 85%. The semilunar or polygonal oligodendrocytes associated with adult myelinated axons contained many organelles indicating a vivid metabolic activity. Domeshaped outbulgings with gap junction-like connections to astrocytic profiles were frequent. Oligodendrocytes surrounded by large myelinated axons and those surrounded by small myelinated axons were cytologically similar. But, thick and thin myelin sheaths had dissimilar periodicities and Marchi-positive myelinoid bodies occurred preferentially in relation to large myelinated axons. We conclude that early oligodendrocytes contact axons and form myelin well before the first expression of T4-O and that emergence of a T4-O immunoreactivity coincides in time with development of a Type IV phenotype. Our data also show that oligodendrocytes associated with thick axons are cytologically similar to cells related to thin axons. In addition, the development of chicken VF white matter was found to be similar to the development of mammalian white matter, except for the rapid time course.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-49235 (URN)10.1023/A:1010994505741 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12Bibliographically approved
    4. Morphology of early developing oligodendrocytes in the ventrolateral chicken spinal cord
    Open this publication in new window or tab >>Morphology of early developing oligodendrocytes in the ventrolateral chicken spinal cord
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    As observed by Del Rio-Hortega (1928), the oligodendroglial population includes Type I and 11 cells related to several thin axons, Type III cells with a few processes in relation to relatively thick axons and Type IV cells related to a single thick axon. This structural diversity of oligodendrocytes is accompanied by a molecular heterogeneity. In the chicken spinal cord oligodendrocytes have begun to contact axons at embryonic day (E)10 and compact sheaths have appeared by E12. AI the latter stage, most sheath-forming oligodendrocytes contact more than one axon. At E15, however, each sheath-forming cell seems to have developed a Schwann cell-like anatomy, being related to a single axon. Against this background, the present study examines the 3D anatomy of early developing oligodendrocytes in the chicken spinal cord. Examination of slices immunostained with antibodies against the oligodendroglial marker 04 showed that a few positive cells are at hand at E6, after which the occurrence increases with age. At E12 most immunostained cells have two or more processes. At E15 however, dye-injected oligodendrocytes have developed a Type IV structure. Between E12 and E15, mean sheath length increases some 4x, from 50 µm to over 200 flm, while the length of the spinal cord increases 36% only. Hence, early oligodendrocytes in chicken white matter develop a Type IV anatomy between E12 and E15 through an elimination of sheaths.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81479 (URN)
    Available from: 2012-09-17 Created: 2012-09-17 Last updated: 2012-09-17Bibliographically approved
  • 18.
    Anderson, Emma S.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bjartmar, Carl
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Eriksson, Cecilia
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Westermark, Gunilla
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Hildebrand, Claes
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Developing chicken oligodendrocytes express the type IV oligodendrocyte marker T4-O in situ, but not in vitro2000In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 284, no 1-2, p. 21-24Article in journal (Refereed)
    Abstract [en]

    Accumulating data suggest that the oligodendrocyte population includes morphological and biochemical subtypes. We recently reported that a polyclonal antiserum against an unknown antigen, the T4-O molecule, labels a subpopulation of chicken oligodendrocytes, obviously representing the type IV variety of Del Rio Hortega. The present study examines the developmental expression of the T4-O molecule in situ and in vitro. The results show that T4-O immunoreactive cells first appear at E15 in the ventral funiculus. But, oligodendrocytes cultured in vitro with or without neurones do not develop a T4-O immunoreactivity. We conclude that oligodendrocytes in the spinal cord of chicken embryos first express the T4-O molecule some time after onset of myelination, and that the T4-O immunoreactive phenotype does not develop in vitro.

  • 19.
    Anderson, Emma S.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bjartmar, Carl
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Hildebrand, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Myelination of prospective large fibres in chicken ventral funiculus2000In: Journal of Neurocytology, ISSN 0300-4864, E-ISSN 1573-7381, Vol. 29, no 10, p. 755-764Article in journal (Refereed)
    Abstract [en]

    In mammals, the oligodendrocyte population includes morphological and molecular varieties. We reported previously that an antiserum against the T4-O molecule labels a subgroup of oligodendrocytes related to large myelinated axons in adult chicken white matter. We also reported that T4-O immunoreactive cells first appear in the developing ventral funiculus (VF) at embryonic day (E)15, subsequently increasing rapidly in number. Relevant fine structural data for comparison are not available in the literature. This prompted the present morphological analysis of developing and mature VF white matter in the chicken. The first axon-oligodendrocyte connections were seen at E10 and formation of compact myelin had started at E12. Between E12 and E15 the first myelinating oligodendrocytes attained a Schwann cell-like morphology. At hatching (E21) 60% of all VF axons were myelinated and in the adult this proportion had increased to 85%. The semilunar or polygonal oligodendrocytes associated with adult myelinated axons contained many organelles indicating a vivid metabolic activity. Domeshaped outbulgings with gap junction-like connections to astrocytic profiles were frequent. Oligodendrocytes surrounded by large myelinated axons and those surrounded by small myelinated axons were cytologically similar. But, thick and thin myelin sheaths had dissimilar periodicities and Marchi-positive myelinoid bodies occurred preferentially in relation to large myelinated axons. We conclude that early oligodendrocytes contact axons and form myelin well before the first expression of T4-O and that emergence of a T4-O immunoreactivity coincides in time with development of a Type IV phenotype. Our data also show that oligodendrocytes associated with thick axons are cytologically similar to cells related to thin axons. In addition, the development of chicken VF white matter was found to be similar to the development of mammalian white matter, except for the rapid time course.

  • 20.
    Anderson, Emma S.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bjartmar, Carl
    Department of Neurosciences, Lerner Research Institue, Cleveland Clinic Foundation, Cleveland, Ohio.
    Westermark, Gunilla
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Hildebrand, Claes
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Molecular heterogeneity of oligodendrocytes in chicken white matter1999In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 27, no 1, p. 15-21Article in journal (Refereed)
    Abstract [en]

    The classical studies by Del Rio Hortega (Mem. Real. Soc. Espan. Hist. Nat. 14:40–122, 1928) suggest that the oligodendrocyte population includes four morphological subtypes. Recent data from the cat and the rat show that the anatomy of oligodendrocytes related to early myelinating prospective large fibers differs from that of oligodendrocytes related to late myelinating prospective small fibers. After application of a polyclonal antiserum to cryostat sections from the chicken CNS, we noted that glial cells in the spinal cord white matter had become labeled. Analysis of the occurrence and cellular localization of this immunoreactivity—the T4-O immunoreactivity—in the CNS of the adult chicken showed that T4-O immunoreactive cells are enriched in the ventral funiculus and superficially in the lateral funiculus of the spinal cord, where they are co-localized with large fibers. Double staining with T4-O antiserum and anti-GFAP or the lectin BSI-B4 revealed that T4-O immunoreactive cells are not astrocytes or microglia. Staining with anti-HSP108, a general marker for avian oligodendrocytes, showed that T4-O immunoreactivity defines an oligodendroglial subpopulation. A search for T4-O immunoreactivity in spinal cord white matter of some other vertebrates revealed that T4-O immunoreactive cells are not present in sections from fish, frog, turtle, rat, and rabbit spinal cord white matter. These results suggest the presence of a fiber size-related molecular heterogeneity among chicken white matter oligodendrocytes.

  • 21.
    Andersson, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Gustafsson, T
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Insulin-like growth factor binding proteins-2 to -6 are expressed by human vascular smooth muscle cells.1999In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 163, no 2, p. 281-288Article in journal (Refereed)
    Abstract [en]

    We have investigated the expression and secretion of insulin-like growth factor binding proteins (IGFBPs-1 to -6) in human vascular smooth muscle cells (hVSMCs) cultured from human renal arteries. Solution hybridization was used to determine IGFBP nRNA levels and Western immunoblot to detect the corresponding peptides. The hVSMCs expressed mRNAs for IGFBPs-2 to -6, IGFBP-1 mRNA was not detected. IGFBPs-3, -4 and -6 mRNAs were the most abundant, IGFBP-5 was also highly expressed, whereas the IGFBP-2 mRNA was just above the limit of detection. Serum starvation for 48 h significantly decreased the mRNA levels of IGFBPs-2 to -5 and tended to decrease IGFBP-6 mRNA also. IGFBPs-2, -4, -5 and -6 peptides could be detected in conditioned medium, but IGFBP-3 peptide was not detected. IGFBP-4 was the only peptide detected without any concentration step. Low-molecular-mass immunoreactive degradation products were found for IGFBPs-2 and -4. Exogenous IGFBPs-1, -3 and -4 in concentrations of 50 ng/ml inhibited DNA synthesis induced by 1 nM IGF-I, whereas IGFBPs-2, -5 and -6 had no significant inhibitory effects at this concentration. We conclude from these results that all IGFBPs except IGFBP-1 are expressed in hVSMC. Our results indicate that locally produced, in addition to circulating,, IGFBPs may have an important role in the regulation of hVSMC.

  • 22.
    Aniansson Zdolsek, Helena
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Holt, Patrick G.
    TVW Telethon Institute for Child Health Research, Perth, Australia.
    Nilsson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Expression of the T–cell markers CD3, CD4 and CD8 in healthy and atopic Children during the first 18 months of life1999In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 119, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    Background: There is little information available about the development of T–cell immunity in healthy and atopic children. We have studied prospectively the mean fluorescence intensity of the T–cell receptor complex–associated CD3, CD4 and CD8 in relation to atopic family history (AFH) and the development of atopic disease.

    Methods: Children with a defined AFH (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 children also at 3, 6 and 12 months. Multicolour flow cytometry was used to analyse pan T–cells (CD3+CD45+CD14–), T–helper–(CD3+CD4+) and T–cytotoxic–(CD3+CD8+) cells.

    Results: At 18 months, 31 children were atopic and 118 non–atopic. Children who developed atopic disease had a higher CD4 expression (mean fluorescence intensity, MFI) on CD4+CD3+ lymphocytes at birth and at 3 months, particularly as compared with non–atopic children without AFH. Furthermore, the CD3 expression on CD3+CD45+CD14– lymphocytes increased more slowly with age in children with double atopic heredity, as compared with children with no or only one atopic family member.

    Conclusions: The higher expression of the CD4 receptor in early infancy in children who developed atopic disease compared with non–atopics suggests a delayed expression in T–helper cells. Children with a strong AFH had a slower increase in the expression of CD3, indicating a delayed T–cell maturation.

  • 23.
    Azerkan, Leila
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Per
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Tømmerås, Karin
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Li, Zhao-Qi
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Characterization of oxyntic glands isolated from the rat gastric mucosa2001In: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 128, no 2, p. 349-357Article in journal (Refereed)
    Abstract [en]

    A simple and reproducible method for isolating oxyntic glands from the rat gastric mucosa was developed. The mucosa was incubated with pronase and EGTA, and then treated mechanically to release glands that were separated from single cells by sedimentation. Parietal cells were identified by immunostaining using a monoclonal antibody against H,K-ATPase. The glandular cells appeared morphologically intact. By careful control of the conditions of gland isolation, long glandular structures comprising hundreds of cells surrounding the lumen were obtained. Intraperitoneal injection of Br-deoxyuridine in the rat 1.5 h before the isolation procedure resulted in glands with a labeling of cells in their neck region. The glands were viable, as demonstrated by their ability to respond to various hormones. Histamine dose-dependently stimulated the acid formation which was measured as the accumulation of [14C]aminopyrine. At 100 microM histamine the accumulation was increased 5-10-fold. At 100 nM, pentagastrin potentiated the histamine stimulated accumulation by approximately 40% but pentagastrin alone did not stimulate. The oxyntic glands obtained by the present procedure appear useful for studies on cell physiology, including regulation of acid secretion, cellular interactions, and possibly also differentiation and proliferation mechanisms since long glandular fragments that contained the proliferative zone could be isolated.

  • 24.
    Bachrach-Lindström, Margaretha
    et al.
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Unosson, Mitra
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Ek, Anna-Christina
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Assessment of nutritional status using biochemical and anthropometric variables in a nutritional intervention study of women with hip fracture2001In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 20, no 3, p. 217-223Article in journal (Refereed)
    Abstract [en]

    Background & Aims: The aim of this study of women with hip fracture was to describe nutritional status with biochemical markers and anthropometric variables, and to evaluate the effect of nutritional intervention with the intention of increasing protein and energy intake.

    Methods: The first consecutive 44 women were included, and used as controls. The next 44 were matched for age, fracture and mental state. Anthropometric variables, IGF-I, hormones and serum albumin were collected 4–6 days (baseline), 1 and 3 months after surgery. Twenty-four women filled out a 7-day food record.

    Results: At baseline, one fourth had BMI <20 kg/m2and subnormal triceps skinfold thickness. Baseline serum albumin, IGF-I and growth hormone levels were low, probably as an acute response to trauma. Women with BMI <20 kg/m2had lower IGF-I levels compared to those with higher BMI. At 3 months, one-third of both groups were protein and energy malnourished. The intervention group obtained higher daily energy percentage from fat but none of the groups reached their calculated energy need.

    Conclusions: Using biochemical markers in the acute postoperative situation to assess nutritional status is not recommended. The intervention had no impact on anthropometric or biochemical variables.

  • 25. Beggs, J
    et al.
    Jordan, S
    Ericson, Ann-Charlott
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Craig, AD
    Synaptology of trigemino- and spinothalamic lamina I terminations in the posterior ventral medial nucleus of the macaque2003In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 459, no 4, p. 334-354Article in journal (Refereed)
    Abstract [en]

    We used the electron microscope to examine lamina I trigemino- and spinothalamic (TSTT) terminations in the posterior part of the ventral medial nucleus (VMpo) of the macaque thalamus. Lamina I terminations were identified by anterograde labeling with biotinylated dextran, and 109 boutons on 38 terminal fibers were closely studied in series of ultrathin sections. Five unlabeled terminal boutons of similar appearance were also examined in detail. Three-dimensional, volume-rendered computer models were reconstructed from complete series of serial sections for 29 boutons on 10 labeled terminal fibers and one unlabeled terminal fiber. In addition, postembedding immunogold staining for GABA was obtained in alternate sections through 23 boutons. Lamina I TSTT terminations in VMpo generally have several large boutons (mean length = 2.16 ╡m, mean width = 1.29 ╡m) that are densely packed with vesicles and make asymmetric synaptic contacts on low-order dendrites of VMpo neurons (mean diameter 1.45 ╡m). They are closely associated with GABAergic presynaptic dendrites (PSDs), and nearly all form classic triadic arrangements (28 of 29 reconstructed boutons). Consecutive boutons on individual terminal fibers make multiple contacts with a single postsynaptic dendrite and can show evidence of progressive complexity. Dendritic appendages that enwrap and invaginate the terminal bouton constitute additional anatomic evidence for secure, high-fidelity synaptic transfer. These observations provide direct ultrastructural evidence supporting the hypothesis that VMpo is a lamina I TSTT thalamocortical relay nucleus in primates that subserves pain, temperature, itch, and other sensations related to the physiological condition of the body.

  • 26.
    Bengtson, Per
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Zetterberg, H.
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Mellberg, T.
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Påhlsson, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Larson, G.
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Characterization of EBV-transformed B-cells established from an individual homozygously mutated (G329A) in the FUT7α1,3-fucosyltransferase gene2005In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 62, no 3, p. 251-258Article in journal (Refereed)
    Abstract [en]

    The α1,3-fucosyltransferase VII (Fuc-TVII) is involved in the biosynthesis of E- and P-selectin ligands such as sialyl Lewis x (SLex) on human leukocytes. Recently, individuals were characterized carrying a missense mutation (G329A; Arg110-Gln) in the FUT7 gene encoding this enzyme. The mutated FUT7 construct produced a Fuc-TVII enzyme with impaired activity compared with the wildtype enzyme. Polymorphonuclear granulocytes from an individual carrying this mutation homozygously also showed a reduced expression of SLex. In the present study, we have established Epstein–Barr virus-transformed B-cell lines from this individual (SIGN) and from an individual not carrying the mutation (IWO). The cell lines were confirmed to be of B-cell origin by flow cytometry analysis. IWO cells interacted with E-selectin in an in vitro flow chamber analysis whereas SIGN cell did not. However, when SIGN cell was transiently transfected with wildtype FUT7 cDNA, interaction with E-selectin could be restored. Cell surface expression of the SLex-related epitopes recognized by antibodies CSLEX-1, KM-93 and HECA-452 was elevated on IWO cells compared with that on SIGN cells, consistent with a role of these antigens in E-selectin recognition. These cell lines will be useful in further characterization of E-selectin ligands and encourage further studies on the consequences of the FUT7-G329A mutation in vivo.

  • 27.
    Bengtsson, Per
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    In vitro studies on cholecystokinin-induced inhibition of acid formation in gastric glands2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The design of methods useful for the preparation of viable glands and cells from the gastric mucosa allowed detailed studies on the mechanisms that regulate gastric acid secretion. The preparation of rabbit gastric glands was the first suitable method to be used and a number of important scientific contributions have been accomplished with this method. Using this method we studied the effect of CCK-like peptides on [14C]aminopyrine accumulation stimulated by histamine, in order to fmd out whether such peptides can inhibit the production of acid in the parietal cell. We also developed a method for the study of viable rat gastric glands that allowed comparative studies in the rat species.

    In rabbit gastric glands CCK-like pep tides inhibited histamine stimulated acid formation whereas gastrin peptides were ineffective. The most potent and efficacious peptides were CCK 8 and the cholecystokinetic amphibian decapeptide cemlein reducing the maximal histamine stimulation of aminopyrine accumulation by 35-38%. The concentration of peptide necessary for eliciting inhibition was in the range of that reported to stimulate amylase secretion in similar in vitro experiments on isolated pancreatic acini, representing a well established physiological function of CCK. Analyses of somatostatin content in the incubation medium revealed that biologically active concentrations of endogenous somatostatin were released into the incubation medium. The rate of somatostatin release increased after CCK 8 or cemlein was added, whereas with G 17, the concentration of somatostatin remained unchanged. In further experiments performed with rabbit mucosal cells prepared from the gastric glands, it was demonstrated that the inhibitory property of CCK 8 only was apparent if a sufficient amount of endocrine cells were present during incubation. In highly purified fractions of parietal cells, however, a small stimulatory effect appeared, a finding that is consistent with similar capacity of gastrin and CCK stimulating the CCK2 receptors present on the parietal cell.

    A method useful for the study of rat gastric glands was developed. The viability of the rat gastric glands appeared excellent as judged by morphological characterisation and functional assessment by means of [14C]aminopyrine accumulation. Upon stimulation with a high dose of histamine the production of acid increased 5-fold over basal. Pentagastrin and CCK 8 were ineffective stimulators per se, but in combination with histamine a marked potentiation occurred. Somatostatin effectively inhibited histamine-stimulated acid formation both in rabbit and rat gastric glands.

    In conclusion, CCK-like peptides inhibit histamine stimulated acid formation in gastric glands prepared from rabbit. The inhibition is mediated in a paracrine-like mode via the release of endogenous somatostatin. A method useful for the study of viable rat gastric glands was developed. In contrast to rabbit gastric glands, CCK 8 potentiated histamine stimulation in rat glands.

    List of papers
    1. Cholecystokinin and Gastrin Inhibit Histamine Stimulated Aminopyrine Uptake in Isolated Rabbit Gastric Glands
    Open this publication in new window or tab >>Cholecystokinin and Gastrin Inhibit Histamine Stimulated Aminopyrine Uptake in Isolated Rabbit Gastric Glands
    1989 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 94, no 2, p. 111-122Article in journal (Refereed) Published
    Abstract [en]

    In the present study we have analyzed if cholecystokinin (CCK) or gastrin (G) can inhibit acid production in isolated rabbit gastric glands as revealed by the aminopyrine technique.

    The results show that G 17 I, CCK 8 NS, CCK 8 S, ceruletide and CCK 39 significantly inhibit histamine induced aminopyrine accumulation. No significant inhibition was noted for G 4, G 34 and NT G 1–13. As a group the CCK peptides were more effective than the gastrin peptides in inhibiting the aminopyrine uptake. CCK 8 S and ceruletide, the most potent inhibitors, reduced histamine induced aminopyrine accumulation with an ED50 of 10−9 and 10−10 M respectively. These potencies are similar to those by which CCK peptides stimulate isolated pancreatic acini to secrete amylase. Inhibition evoked by CCK 8 S was most effective following 20–40 min of incubation time, possibly indicating that the effect is mediated by the release of an intermediate substance.

    The results may therefore indicate a role for cholecystokinin as a physiological inhibitor of acid secretion in the rabbit. The results may also contribute to explain why the potent gastric secretagogue gastrin per se fails to stimulate acid formation in gastric glands isolated from the rabbit.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-79779 (URN)10.3109/03009738909178556 (DOI)
    Available from: 2012-08-14 Created: 2012-08-14 Last updated: 2017-12-07Bibliographically approved
    2. Inhibition of acid formation and stimulation of somatostatin release by cholecystokinin-related peptides in rabbit gastric glands
    Open this publication in new window or tab >>Inhibition of acid formation and stimulation of somatostatin release by cholecystokinin-related peptides in rabbit gastric glands
    1989 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 419, p. 765-774Article in journal (Refereed) Published
    Abstract [en]

    1. The purpose of the present study was to investigate the role of somatostatin in the inhibition of acid production induced by caerulein and cholecystokinin (CCK) in isolated rabbit gastric glands. Acid production was estimated by the aminopyrine technique.

    2. Exogenous somatostatin 14 and somatostatin 28 (10(-7) M) reduced to a similar extent the aminopyrine uptake produced by 5 x 10(-5) M-histamine during the course of 40 min incubation.

    3. Significant inhibition of histamine-stimulated aminopyrine accumulation occurred at a somatostatin 14 concentration of 10(-9) M.

    4. Caerulein and CCK octapeptide (10(-13)-10(-7) M) were found to release somatostatin from isolated gastric glands in a dose-dependent manner. The dose-response relationships for somatostatin release and inhibition of aminopyrine uptake were similar. Thus, the half-maximal dose approximations for somatostatin release and inhibition of aminopyrine uptake were 0.5 and 1.4 x 10(-9) M respectively for CCK octapeptide and 0.9 and 2.5 x 10(-11) M for caerulein. Heptadecapeptide gastrin proved to be a very poor releaser of somatostatin in the system used. The CCK octapeptide-induced somatostatin release was time dependent and the concentrations of somatostatin that accumulated in the incubation medium were similar to those of exogenous somatostatin that were needed to evoke inhibition.

    5. The present results support the concept that cholecystokinin inhibits gastric acid secretion by releasing somatostatin from endocrine-like cells in the gastric mucosa. It is suggested that cholecystokinin-related peptides may play a physiological role in inhibiting gastric acid secretion. A similar role for gastrin is not supported by the present study.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-79780 (URN)2576071 (PubMedID)
    Available from: 2012-08-14 Created: 2012-08-14 Last updated: 2017-12-07Bibliographically approved
    3. Characterization of oxyntic glands isolated from the rat gastric mucosa
    Open this publication in new window or tab >>Characterization of oxyntic glands isolated from the rat gastric mucosa
    Show others...
    2001 (English)In: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 128, no 2, p. 349-357Article in journal (Refereed) Published
    Abstract [en]

    A simple and reproducible method for isolating oxyntic glands from the rat gastric mucosa was developed. The mucosa was incubated with pronase and EGTA, and then treated mechanically to release glands that were separated from single cells by sedimentation. Parietal cells were identified by immunostaining using a monoclonal antibody against H,K-ATPase. The glandular cells appeared morphologically intact. By careful control of the conditions of gland isolation, long glandular structures comprising hundreds of cells surrounding the lumen were obtained. Intraperitoneal injection of Br-deoxyuridine in the rat 1.5 h before the isolation procedure resulted in glands with a labeling of cells in their neck region. The glands were viable, as demonstrated by their ability to respond to various hormones. Histamine dose-dependently stimulated the acid formation which was measured as the accumulation of [14C]aminopyrine. At 100 microM histamine the accumulation was increased 5-10-fold. At 100 nM, pentagastrin potentiated the histamine stimulated accumulation by approximately 40% but pentagastrin alone did not stimulate. The oxyntic glands obtained by the present procedure appear useful for studies on cell physiology, including regulation of acid secretion, cellular interactions, and possibly also differentiation and proliferation mechanisms since long glandular fragments that contained the proliferative zone could be isolated.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24920 (URN)10.1016/S1095-6433(00)00309-3 (DOI)11223396 (PubMedID)9324 (Local ID)9324 (Archive number)9324 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Effects of cholecystokinin on acid formation in glands and cells isolated from rabbit and rat gastric mucosa
    Open this publication in new window or tab >>Effects of cholecystokinin on acid formation in glands and cells isolated from rabbit and rat gastric mucosa
    Show others...
    2000 (English)In: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 126, no 1, p. 77-84Article in journal (Refereed) Published
    Abstract [en]

    Isolated gastric glands and isolated cells prepared from rabbit and rat were studied to analyse the influence of cholecystokinin octapeptide (CCK 8) on histamine stimulated parietal cell acid formation as assessed by [14C]aminopyrine sequestered in acid tissue compartments. In rabbit gastric glands, CCK 8 evoked 32±6% (P<0.01) inhibition of histamine stimulated acid formation, whereas in glands prepared from rat no inhibition was recorded. Instead, CCK 8 seemed to induce a variable increase of the histamine stimulation in rat gastric glands as the aminopyrine accumulation was increased by 110±46% (P<0.1). Further studies on cell preparations derived from rabbit gastric mucosa revealed dual properties of CCK 8, eliciting either inhibition or stimulation of the parietal cell depending on the presence of endocrine cells. The results show that paracrine communication may be effective in glandular preparations, but seems to vary depending on species.

    Keywords
    Inhibition of acid, Acid secretion, Fundic glands, In vitro, Paracrine function, Parietal cells, Histamine stimulation, Somatostatin
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24925 (URN)10.1016/S1095-6433(00)00188-4 (DOI)10908854 (PubMedID)9330 (Local ID)9330 (Archive number)9330 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 28.
    Bengtsson, Per
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Azerkan, Leila
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Lundqvist, Gudmar
    Department of Clinical Chemistry, Academic Hospital, Uppsala, Sweden.
    Nilsson, Göran
    Department of Physiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Effects of cholecystokinin on acid formation in glands and cells isolated from rabbit and rat gastric mucosa2000In: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 126, no 1, p. 77-84Article in journal (Refereed)
    Abstract [en]

    Isolated gastric glands and isolated cells prepared from rabbit and rat were studied to analyse the influence of cholecystokinin octapeptide (CCK 8) on histamine stimulated parietal cell acid formation as assessed by [14C]aminopyrine sequestered in acid tissue compartments. In rabbit gastric glands, CCK 8 evoked 32±6% (P<0.01) inhibition of histamine stimulated acid formation, whereas in glands prepared from rat no inhibition was recorded. Instead, CCK 8 seemed to induce a variable increase of the histamine stimulation in rat gastric glands as the aminopyrine accumulation was increased by 110±46% (P<0.1). Further studies on cell preparations derived from rabbit gastric mucosa revealed dual properties of CCK 8, eliciting either inhibition or stimulation of the parietal cell depending on the presence of endocrine cells. The results show that paracrine communication may be effective in glandular preparations, but seems to vary depending on species.

  • 29. Berg, Anders
    et al.
    Bergendahl, Christina
    Lundberg, Bruno
    Tibell, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Benefiting from an open-ended experiment? A comparison of attitudes to, and outcomes of, an expository versus an open-inquiry version of the same experiment2003In: International Journal of Science Education, ISSN 0950-0693, E-ISSN 1464-5289, Vol. 25, no 3, p. 351-372Article in journal (Refereed)
    Abstract [en]

    In this article we compare outcomes of an open-inquiry and an expository version of a chemistry laboratory experiment at university level for 190 students. The aim of the study was to investigate if these two versions would result in different outcomes depending on the students' attitudes towards learning. We used a questionnaire to find out their attitude position prior to the laboratory experiment. The outcome in the different version of the experiment was evaluated by interviews, questions asked during the experiment and students self-evaluations. The main findings were that the open-inquiry version shows the most positive outcomes regarding learning outcome, preparation time, time spent in the laboratory and student perception of the experiment. The students with low attitude position needed more support to meet the challenge of an open-inquiry experiment, the support being a clearer explanation of the aims, and feedback from the instructor during the experiment.

  • 30.
    Berg, Anna
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Effects of nitric oxide on gastric acid secretion in human gastric mucosa: functional and morphological studies2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Hydrochloric acid (HCI) is secreted in high amounts by parietal cells in the human gastric mucosa and the resulting low pH constitutes an important factor for creating a suitable environment for the digestion. The normal gastric mucosa is equipped with an arsenal of protective mechanisms against the extreme chemical environment which the gastric acid creates. There are situations when the barrier function of the gastric mucosa is disrupted and gastric acid becomes potentially deleterious. Understanding the regulatory mechanisms by which the secretion of gastric acid is controlled under physiological conditions may improve future treatment in peptic ulcers, gastritis and other gastric inflammatory disorders.

    Nitric oxide (NO) has previously been found to regulate gastric acid secretion in animals. Immunohistochemical investigation of normal human gastric mucosa revealed that hitherto unknown endocrine cells in the oxyntic mucosa express nitric oxide synthase (NOS). These cells were found located in close contact with parietal cells, which suggests a paracrine effect of NO on parietal cell function.

    Functional studies of the effects of exogenous and endogenous NO on stimulated gastric acid secretion were performed on isolated human gastric glands. Indirect determination of gastric acid secretion by using the 14C-labeled aminopyrine (AP) technique was used. Stimulation was induced by administration of histamine or db-cAMP. Secretagogue-induced AP-accumulation in gastric glands treated with NO-donor was significantly decreased compared with untreated glands. This indicates that exogenously administered NO inhibits stimulated gastric acid secretion in humans. Inhibition of endogenous NO-production by the use of NOS-inhibitors caused an increase in AP-accumulation, which suggests that NO released from cells within the glandular epithelium exerts a physiological effect in acting as an inhibitor of stimulated gastric acid secretory activity in humans.

    Further functional and morphological investigations showed that exogenously administered cGMP induced a concentration-dependent inhibition of AP-accumulation in isolated human gastric glands similar to that induced by NO-donors. When soluble guanylate cyclase (sGC), a common target enzyme for NO, was blocked NO failed to induce inhibition. Biochemical analysis of the cGMP concentrations in isolated gastric glands after treatment with NO-donor revealed that inhibition of AP-accumulation due to NO is accompanied by an increase in glandular cGMP content. This increase was localized by immunohistochemistry to the parietal cells. These results indicates that NO inhibits secretagogue-induced gastric acid secretion in isolated human gastric glands via activation of sGC, which results in an increased concentration of cGMP in the parietal cells.

    In order to determine the cGMP-dependent mechanisms leading to diminished output of gastric acid, parietal cells were investigated with emphasis on the cytological transformations associated with stimulation of acid secretion. Isolated human gastric glands were treated with NO-donor prior to administration of histamine. The cytoskeletal rearrangement as well as the translocation and incorporation of H+/K+-ATPase into the apical membrane was studied using con focal and electron microscopy techniques. Results showed that histamine-induced F-actin rearrangement as well as the translocation of H+/K+-ATPase rich tubulovesicles to the canalicular membrane, and their fusion with the same, was unaffected by NO. The secretory canaliculi, which swell to great size as a result of histamine-treatment, were however small and unexpanded in response to treatment with NO-donor. The unexpanded canaliculi reflected the NO-induced inhibition of secretion of HCI observed in the functional studies.

    In conclusion, these results show that NO may be a physiological regulator of stimulated gastric acid secretion in humans and that this inhibition is a cGMP-dependent mechanisms which diminishes output of HCI from parietal cells without affecting stimuli-induced cytological transformations.

    List of papers
    1. Morphological support for paracrine inhibition of gastric acid secretion by nitric oxide in humans
    Open this publication in new window or tab >>Morphological support for paracrine inhibition of gastric acid secretion by nitric oxide in humans
    2001 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 36, no 10, p. 1016-1021Article in journal (Refereed) Published
    Abstract [en]

    Background: Functional studies have shown that nitric oxide (NO) inhibits gastric acid secretion in a variety of species, including man. We have performed a morphological study with the intention of localizing the endothelial NO synthase (eNOS) in the human gastric mucosa.

    Methods: Fifteen healthy subjects voluntarily participated in the study, and mucosal biopsies were obtained from the cardia, corpus and antrum. The presence and localization of eNOS were studied using immunohistochemical techniques.

    Results: eNOS-immunoreactivity (eNOS-IR) is found in surface mucous cells of cardia, corpus and antrum. Unique to the oxyntic mucosa is the presence of eNOS-IR in 'endocrine-like' cells, found in close contact with parietal cells.

    Conclusions: eNOS-IR cells in close apposition to parietal cells provide morphological support for paracrine inhibition of gastric acid secretion by NO.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24926 (URN)10.1080/003655201750422594 (DOI)9331 (Local ID)9331 (Archive number)9331 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Nitric oxide-an endogenous inhibitor of gastric acid secretion in isolated human gastric glands
    Open this publication in new window or tab >>Nitric oxide-an endogenous inhibitor of gastric acid secretion in isolated human gastric glands
    2004 (English)In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 4, no 16Article in journal (Refereed) Published
    Abstract [en]

    Background

    Endothelial nitric oxide synthase (eNOS) has previously been detected in the glandular part of the human gastric mucosa. Furthermore, nitric oxide (NO) has been shown to influence gastric secretion in various animal models. The present study was conducted to investigate the influence of exogenously and endogenously derived NO on histamine- and cAMP-stimulated gastric acid secretion in isolated human oxyntic glands.

    Methods

    Oxyntic glands were isolated from human gastric biopsies and were subsequently pre-treated with NO donors and nitric oxide synthase inhibitors and then exposed to histamine or dibutyryl-cAMP (db-cAMP). The secretory response of the glands was determined as accumulation of [14C]aminopyrine.

    Results

    The histamine- or db-cAMP-induced acid secretion was attenuated by L-arginine, a known source of endogenous NO, and also by the NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP). Pre-treatment with either of the NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME) or NG-nitro-L-arginine (L-NNA) enhanced the secretory response.

    Conclusion

    Our results show that NO inhibits gastric acid secretion in isolated human gastric glands, and that there is endogenous formation of NO within the glandular epithelium in the vicinity of the parietal cells.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-22394 (URN)10.1186/1471-230X-4-16 (DOI)1604 (Local ID)1604 (Archive number)1604 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands
    Open this publication in new window or tab >>Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands
    Show others...
    2005 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 289, no 6, p. G1061-G1066Article in journal (Refereed) Published
    Abstract [en]

    We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [14C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso-N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-31485 (URN)10.1152/ajpgi.00230.2005 (DOI)17277 (Local ID)17277 (Archive number)17277 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
    4. Effect of nitric oxide on histamine-induced cytological transformations in parietal cells in isolated human gastric glands
    Open this publication in new window or tab >>Effect of nitric oxide on histamine-induced cytological transformations in parietal cells in isolated human gastric glands
    2007 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 52, no 1, p. 126-136Article in journal (Refereed) Published
    Abstract [en]

    Previous studies have shown that nitric oxide (NO) inhibits histamine-induced gastric acid secretion in isolated human gastric glands. NO synthase has been found to be present in the human oxyntic mucosa and has been suggested to serve as a paracrine regulator of gastric acid secretion. Histamine stimulation of parietal cells induces cytoskeletal rearrangements, recruitment of H +/K +-ATPase-rich tubulovesicles to the apical membrane and expansion of intracellular canaliculi. The aim of the present study was thus to investigate (i) the effect of an NO donor on histamine-induced cytological transformations and (ii) the influence of increased [Ca 2+] i on NO-induced morphological changes in human parietal cells. Human gastric glands were isolated and subjected to the NO donor SNAP prior to histamine administration. [Ca 2+] i was increased by photolysis of the caged Ca 2+ compound NP-EGTA. The distribution of F-actin, ezrin, and H +/K +-ATPase was assessed by confocal microscopy. Ultrastructural analysis was performed using transmission electron microscopy. SNAP did not influence the histamine-induced translocation of F-actin, ezrin, and H +/K +-ATPase but prevented an increase in the canalicular size. Elevation of [Ca 2+] i in resting cells was found to mimic histamine-induced intraparietal cell transformations; however, NO-induced parietal cell morphology was unaffected by a rise in [Ca 2+] i. These results indicate that NO inhibits secretion of fluid into the canalicular lumen without affecting membrane recruitment and that this effect is Ca 2+-insensitive. © 2006 Springer Science+Business Media, Inc.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-40472 (URN)10.1007/s10620-006-9439-z (DOI)53339 (Local ID)53339 (Archive number)53339 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
  • 31.
    Berg, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Kechagias, Stergios
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Sjöstrand, Sven-Erik
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Morphological support for paracrine inhibition of gastric acid secretion by nitric oxide in humans2001In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 36, no 10, p. 1016-1021Article in journal (Refereed)
    Abstract [en]

    Background: Functional studies have shown that nitric oxide (NO) inhibits gastric acid secretion in a variety of species, including man. We have performed a morphological study with the intention of localizing the endothelial NO synthase (eNOS) in the human gastric mucosa.

    Methods: Fifteen healthy subjects voluntarily participated in the study, and mucosal biopsies were obtained from the cardia, corpus and antrum. The presence and localization of eNOS were studied using immunohistochemical techniques.

    Results: eNOS-immunoreactivity (eNOS-IR) is found in surface mucous cells of cardia, corpus and antrum. Unique to the oxyntic mucosa is the presence of eNOS-IR in 'endocrine-like' cells, found in close contact with parietal cells.

    Conclusions: eNOS-IR cells in close apposition to parietal cells provide morphological support for paracrine inhibition of gastric acid secretion by NO.

  • 32.
    Berg, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Redéen, Stefan
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Sjöstrand, Sven-Erik
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Nitric oxide-an endogenous inhibitor of gastric acid secretion in isolated human gastric glands2004In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 4, no 16Article in journal (Refereed)
    Abstract [en]

    Background

    Endothelial nitric oxide synthase (eNOS) has previously been detected in the glandular part of the human gastric mucosa. Furthermore, nitric oxide (NO) has been shown to influence gastric secretion in various animal models. The present study was conducted to investigate the influence of exogenously and endogenously derived NO on histamine- and cAMP-stimulated gastric acid secretion in isolated human oxyntic glands.

    Methods

    Oxyntic glands were isolated from human gastric biopsies and were subsequently pre-treated with NO donors and nitric oxide synthase inhibitors and then exposed to histamine or dibutyryl-cAMP (db-cAMP). The secretory response of the glands was determined as accumulation of [14C]aminopyrine.

    Results

    The histamine- or db-cAMP-induced acid secretion was attenuated by L-arginine, a known source of endogenous NO, and also by the NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP). Pre-treatment with either of the NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME) or NG-nitro-L-arginine (L-NNA) enhanced the secretory response.

    Conclusion

    Our results show that NO inhibits gastric acid secretion in isolated human gastric glands, and that there is endogenous formation of NO within the glandular epithelium in the vicinity of the parietal cells.

  • 33.
    Berg, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Redéen, Stefan
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Grenegård, Magnus
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Sjöstrand, Sven-Erik
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands2005In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 289, no 6, p. G1061-G1066Article in journal (Refereed)
    Abstract [en]

    We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [14C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso-N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.

  • 34.
    Berg, Anna
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Redéen, Stefan
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Sjöstrand, Sven-Erik
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Effect of nitric oxide on histamine-induced cytological transformations in parietal cells in isolated human gastric glands2007In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 52, no 1, p. 126-136Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown that nitric oxide (NO) inhibits histamine-induced gastric acid secretion in isolated human gastric glands. NO synthase has been found to be present in the human oxyntic mucosa and has been suggested to serve as a paracrine regulator of gastric acid secretion. Histamine stimulation of parietal cells induces cytoskeletal rearrangements, recruitment of H +/K +-ATPase-rich tubulovesicles to the apical membrane and expansion of intracellular canaliculi. The aim of the present study was thus to investigate (i) the effect of an NO donor on histamine-induced cytological transformations and (ii) the influence of increased [Ca 2+] i on NO-induced morphological changes in human parietal cells. Human gastric glands were isolated and subjected to the NO donor SNAP prior to histamine administration. [Ca 2+] i was increased by photolysis of the caged Ca 2+ compound NP-EGTA. The distribution of F-actin, ezrin, and H +/K +-ATPase was assessed by confocal microscopy. Ultrastructural analysis was performed using transmission electron microscopy. SNAP did not influence the histamine-induced translocation of F-actin, ezrin, and H +/K +-ATPase but prevented an increase in the canalicular size. Elevation of [Ca 2+] i in resting cells was found to mimic histamine-induced intraparietal cell transformations; however, NO-induced parietal cell morphology was unaffected by a rise in [Ca 2+] i. These results indicate that NO inhibits secretion of fluid into the canalicular lumen without affecting membrane recruitment and that this effect is Ca 2+-insensitive. © 2006 Springer Science+Business Media, Inc.

  • 35.
    Bergman, Hanna
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Intraocular and intracranial transplantation of neural tissue: Studies on hypothalamic and hippocampal neuros1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Previous studies has demonstrated the possibility to transplant monoaminergic neurons intracranially and to the anterior chamber of the eye, where these neurons continue to develop into functional, transmitter expressing cells. In the present study, investigations were undertaken to examine the development of transplanted hypothalamic and hippocampal neurons in the rat. The intention was to examine synaptic maturation in the isolated brain tissue and the possibility of histaminergic neurons to survive transplantation intraocularly and intracranially into the denervated hippocampus. Properties such as fiber ingrowth into eo-transplanted tissue, electrophysiological activity and histaminergic H3-receptor response, and influence of hypothalamic tissue on eo-transplanted tissues were evaluated. Synaptic maturation was studied using an immunoblot assay of the synapsin I and II proteins and synapsin immunohistochemistry. The hypothalamic grafts were examined with immunohistochemistry and histamine assay of the levels of histamine in the transplants. Electrophysiological recordings of single cell activity was used to study the effect of H3-receptor agonist and antagonist. The isolated intra ocular transplants of hippocampal tissue developed significant amounts of synapsin proteins with an overall distribution pattern as in the hippocampus in situ. Histaminergic neurons in the hypothalamic transplants survived transplantation both intraocularly and intracranially. The neurons were found to send neurites into the host iris and into eo-grafted CNS tissue. The hypothalamic transplants were also found to have a stimulatory effect on the growth of eo-grafted hippocampal tissue and on pyramidal cell differentiation. Neurons within the hypothalamic transplants exhibited spontaneous activity that was suppressed upon agonist stimulation of H3-receptors. These findings demonstrate that histaminergic neurons grow and develop in transplanted hypothalamic tissue and that neurons in these transplants expressed histamine and functional H3-receptors.

  • 36.
    Bergman, Malin
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Ahnström, Marie
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Palmebäck Wegman, Pia
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Polymorphism in the manganese superoxide dismutase (MnSOD) gene and risk of breast cancer in young women2005In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 131, no 7, p. 439-444Article in journal (Refereed)
    Abstract [en]

    Purpose: Manganese superoxide dismutase (MnSOD) is one of the major enzymes implicated in the cellular defence against reactive oxygen species. Low expression of MnSOD has been observed in different cancer tissues and several reports have shown that overexpression of MnSOD inhibits growth in various human cancer cells. These observations suggest that MnSOD is involved in carcinogenesis. A polymorphism (Ala-9Val) in the mitochondrial targeting sequence (MTS) of the MnSOD gene has been proposed to affect protein localization and thereby influence cellular defence against superoxide radicals.

    Methods: In the present case-control study, including 118 early onset breast cancer patients (≤36 years) and 174 age-matched controls, the MTS polymorphism and loss of heterozygosity (LOH) in the locus of MnSOD were analysed.

    Results: We found that individuals with MnSODVal/Val and MnSODVal/Ala genotypes showed an increased risk of breast cancer (OR, 2.7; 95% CI, 2.2–5.5, p=0.01, OR, 3.0; 95%CI, 1.4–6.5, p=0.002). Moreover, 45% of the informative cases expressed allelic loss at the chromosomal locus of the MnSOD gene. No correlation was found between LOH and the genotype.

    Conclusion: The present study suggests that MnSOD may be implicated in breast carcinogenesis in young women.

  • 37.
    Bergman-Jungeström, Malin
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Gentile, Massiliano
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Lundin, Anna-Carin
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Association between CYP17 gene polymorphism and risk of breast cancer in young women1999In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 84, p. 350-353Article in journal (Refereed)
    Abstract [en]

    Long-term exposure to oestrogens is a well-recognised risk factor for breast cancer, whereas little is known about the influence of polymorphisms of genes involved in oestrogen biosynthesis and metabolism. A candidate, containing a single bp polymorphism, T→C, (designated, A2 allele), might be the CYP17 gene, which codes for an enzyme involved in oestrogen synthesis. This polymorphism creates an additional Sp1-type promoter site (CCACC box), which has been shown to be associated with increased serum oestrogen levels. We performed a case-control study, to evaluate association of the CYP17 gene polymorphism with risk of breast cancer in young women (younger than 37 years). We found a statistically significant increased risk in carriers of at least 1 A2 allele [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.1–3.5, p = 0.027], and a trend toward a gene-dose effect illustrated by a slightly higher risk for A2-homozygous subjects (OR, 2.8) than for heterozygous women (OR, 1.9). Furthermore, when we investigated the CYP17 genotype in relation to tumour characteristics, breast cancer patients with 1 or 2 A2 alleles tended to have lower oestrogen receptor levels (risk ratio, 0.70; CI, 0.41–1.2, p = 0.44). Our findings suggest that CYP17 gene polymorphism influences breast carcinogenesis in young women.

  • 38. Bergström, Joakim
    et al.
    Murphy, Charles
    Eulitz, Manfred
    Weiss, Deborah
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Solomon, Alan
    Westermark, Per
    Codeposition of apolipoprotein A-IV and transthyretin in senile systemic (ATTR) amyloidosis2001In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 285, no 4, p. 903-908Article in journal (Refereed)
    Abstract [en]

    Protein material was extracted from amyloid-rich sections of formalin-fixed and paraffin-embedded heart tissue from an individual with senile systemic amyloidosis, known to contain wild-type transthyretin as major amyloid fibril protein. Amino acid sequence analysis of tryptic peptides of this material revealed in addition to transthyretin sequences, also amino acid sequence corresponding to an N-terminal fragment of apolipoprotein A-IV. In immunohistochemistry, an antiserum to a synthetic apolipoprotein A-IV peptide labeled amyloid specifically. This peptide formed spontaneously amyloid-like fibrils in vitro and enhanced fibril formation from wild-type transthyretin. We conclude that several apolipoproteins, including apolipoprotein A-IV, may be important minor amyloid constituents, promoting fibril formation.

  • 39.
    Björnström, Karin
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Holmgren, Susanna
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Loverock, A.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Wijkman, Magnus
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Lindroth, Margareta
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Rho and Rho Kinase are involved in the signal transduction cascade caused by propofolManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Propofol is known to interact with the γ-aminobutyric acidA (GABAA) receptor, however, activating the receptor alone is not sufficient for producing anaesthesia. Propofol tyresine phosphorylates the GABAA receptor and reorganises the actin cytoskeleton, eausing ring structures and rnembrane ruffles. Propofol, but not GABA, the endogenous tigand for the GABAA receptor, tyresine phosphorylates actin, both in the membrane and cytoskeletal fractions of the neuron.

    Aim: How does propofol cause the actin reorganisation and is this a specific effect of propofol? Is the small membrane associated G-protein rho involved in the signal cascade towards the actin reorganisation?

    Methods: Westem blotting (WB) was used to visualize tyresine phosphorylated immunoprecipitated proteins and changes in actin between the different cellularcompartments after inhibition with rho (C3 exotoxin) and rho kinase (ROK) (HA-1077) inhibitors. Fluoreseenee mireoscopy after rhodamine-phalloidin labelling of actin was used to calculate the number of actin ring structures caused by propofol or GABA, in same experiments combined with pre-incubation with C3 exotoxin, HA- 1077 or the tyrosine kinase inhibitor Herbimycin A. Propofol-stimulated cells were studied with confocal microscopy.

    Results: Propofol eaused an increased tyresine phosphorylation, that was reduced by C3 exotoxin, of a 160 kDa protein after two minutes stimulation. The 160 kDa protein is still unidentified. The actin ring structures caused by propofol was shown with confocal microscopy to go almost through the entire cell. The amount of rings were reduced by C3 exatoxin as well as HA-1077. Furthermore, w hen a tyrosine kinase bioeker was used no ring structures were formed. However, GABA did not produce any ring structures. When the actin content of the cellular campartments were analysed, C3 exatoxin treated cells showed an increased amount of actin in the cytoskeletal fraction, simultaneausly with a decrease in both the membrane and the cytosol fractions. The ROK bioeker on ly eaused a reduction of actin in the cytosol/membrane fractions, but no increase was observed in the cytoskeleton.

    Conclusion: Propofol, but not GABA, eauses actin ring structures in neurons. Propofol uses the rho and rho kinase pathway to reorganize the actin cytoskeleton into ring structures, which is also dependent on a tyresine klnase. Propofol also eauses an unidentified rho dependent 160 kDa protein to be tyresine phosphorylated. The activation eaused by propofol of rho and rho kinase causes actin to be moved from the cytoskeleton to the cell membrane and cytosol. This reorganisation of actin might influence the GABAA receptor by keeping it open, thus allowing the cell to be hyperpolarized for longer time, and consequently maintain anaesthesia.

  • 40.
    Björnström, Karin
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Sjölander, Anita
    Division of Experimental Pathology, Lund University, Malmö, Sweden.
    Schippert, Åsa
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    A tyrosine kinase regulates propofol-induced modulation of the β-subunit of the GABAA receptor and release of intracellular calcium in cortical rat neurones2002In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 175, no 3, p. 227-235Article in journal (Refereed)
    Abstract [en]

    Propofol, an intravenous anaesthetic, has been shown to interact with the β-subunit of the γ-amino butyric acidA (GABAA) receptor and also to cause changes in [Ca2+]i. The GABAA receptor, a suggested target for anaesthetics, is known to be regulated by kinases. We have investigated if tyrosine kinase is involved in the intracellular signal system used by propofol to cause anaesthesia. We used primary cell cultured neurones from newborn rats, pre-incubated with or without a tyrosine kinase inhibitor before propofol stimulation. The effect of propofol on tyrosine phosphorylation and changes in [Ca2+]i were investigated. Propofol (3 μg mL−1, 16.8 μM) increased intracellular calcium levels by 122 ± 34% (mean ± SEM) when applied to neurones in calcium free medium. This rise in [Ca2+]i was lowered by 68% when the cells were pre-incubated with the tyrosine kinase inhibitor herbimycin A before exposure to propofol (P < 0.05). Propofol caused an increase (33 ± 10%) in tyrosine phosphorylation, with maximum at 120 s, of the β-subunit of the GABAA-receptor. This tyrosine phosphorylation was decreased after pre-treatment with herbimycin A (44 ± 7%, P < 0.05), and was not affected by the absence of exogenous calcium in the medium. Tyrosine kinase participates in the propofol signalling system by inducing the release of calcium from intracellular stores and by modulating the β-subunit of the GABAA-receptor.

  • 41.
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Acta Gyllenbergiana IV.Psyche, soma and pain.Editors Eija Kalso, Ann-Mari Estlander and Matti Klockars.2003In: Skriv in din egen text för ej reg. tidskrift etc.,2003, 2003, p. 59-72Conference paper (Refereed)
  • 42.
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Sex hormones and pain: A new role for brain aromatase?2000In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 423, no 4, p. 549-551Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 43.
    Blomqvist, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Craig, A D (Bud)
    Is neuropathic pain caused by the activation of nociceptive-specific neurons due to anatomic sprouting in the dorsal horn?2000In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 428, no 1Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 44.
    Blomqvist, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Zhang, En-Tan
    Craig, A D (Bud)
    Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus2000In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 123, no 3, p. 601-619Article in journal (Refereed)
    Abstract [en]

    Previous studies in the macaque monkey have identified a thalamic nucleus, the posterior portion of the ventral medial nucleus (VMpo), as a dedicated lamina I spinothalamocortical relay for pain and temperature sensation. The dense plexus of calbindin-immunoreactive fibres that characterizes VMpo in primates enables its homologue to be identified in the human thalamus by immunohistochemical labelling for calbindin. We have now analysed in detail the cytoarchitectonic characteristics of VMpo and its relationship with immunoreactivity for calbindin, substance P and calcitonin gene-related peptide (CGRP) in the human thalamus. The area in the posterolateral thalamus in which dense calbindin-immunoreactive fibre terminations are present coincides nearly completely with a distinct region that contains small to medium-sized cells with round or oval shapes that are aggregated in clusters separated by cell sparse areas. This region, which we identify as VMpo, is located posteromedial to the ventral posterior lateral (VPL) and ventral posterior medial (VPM) nuclei, ventral to the anterior pulvinar and centre median nuclei, lateral to the limitans and parafascicular nuclei and dorsal to the medial geniculate nucleus. Calbindin-immunoreactive fibres enter VMpo from the spinal lemniscus and form large patches of dense terminal-like staining over clusters of VMpo neurons. A few of these clusters also display terminal-like substance P labelling. Small bursts of CGRP staining are intercalated between the calbindin-labelled clusters, but there is little or no overlap between these two markers. CGRP inmunoreactivity is also present over small, non-clustered neurons in the calbindin-negative area that separates VMpo from the VPL and VPM nuclei, which we denote as the posterior nucleus (Po). These observations provide a concise description of VMpo in the human thalamus. Further, they suggest that the lamina I spinothalamic tract fibres (represented by calbindin and probably also substance P immunoreactivity) and vagal-solitary-parabrachial afferents (represented by CGRP immunoreactivity) form closely related, but separate, termination fields that can be considered to represent different aspects of enteroceptive information regarding the physiological status of the tissues and organs of the body. The location of VMpo and the adjacent Po fits with clinical descriptions of the thalamic area from which pain, temperature and visceral sensations can be evoked by microstimulation, and where nociceptive and thermoreceptive neurons have been recorded in humans. It also corresponds to the area in which infarcts cause analgesia and thermoanaesthesia and can lead to the paradoxical development of central pain.

  • 45. Bojestig, M
    et al.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Karlberg, Bengt E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes2000In: jraas. Journal of the renin-angiotensin-aldosterone system, ISSN 1470-3203, E-ISSN 1752-8976, Vol. 1, no 4, p. 353-356Article in journal (Refereed)
    Abstract [en]

    Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA1c during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA1c. >8.4% compared with those with mean HbA1c 7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.

  • 46.
    Borch, Kurt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Grodzinsky, Ewa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Petersson, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery.
    Jönsson, Kjell-Åke
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Valdimarsson, Trausti
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Prevalence of coeliac disease and relations to Helicobacter pylori infection and duodenitis in a Swedish adult population sample: A histomorphological and serological survey2000In: InflammoPharmacology, ISSN 0925-4692, E-ISSN 1568-5608, Vol. 8, no 4, p. 341-350Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to determine the prevalence of coeliac disease and its relation to duodenitis, H. pylori infection and gastritis in a sample of the adult general population. Methods: A Swedish population sample of 482 subjects (aged 35 to 85 years) were examined with gastro-duodenoscopy with multiple biopsies taken. Circulating antibodies to endomycium, gliadin, and H. pylori were also determined. Results: Based on histomorphological findings, coeliac disease was evident in 9 of 482 subjects giving a prevalence of 1.9 [1.0-4.0, 95% confidence interval] percent. The prevalence of gastritis with or without H. pylori infection did not differ between subjects with and without coeliac disease. Considering subjects without coeliac disease, there was no difference in the serum levels of gliadin antibodies between those with and without duodenitis. However, subjects with positive H. pylori status had significantly higher levels of gliadin antibodies than those with negative H. pylori status. Conclusions: This study confirms that there is a relatively high prevalence of undiagnosed coeliac disease in Swedish adults. There was no association between coeliac disease and H. pylori infection or gastritis, although serum gliadin antibody levels were slightly increased in subjects with positive H. pylori status.

  • 47. Borg, H
    et al.
    Björk, E
    Bolinder, J
    Eriksson, JW
    Nyström, L
    Jeppsson, J-O
    Sundkvist, G
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 yrs) in the Diabetes Incidence Study in Sweden (DISS)2003In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 46, no 2, p. 173-181Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis. We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years. Methods. During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide. Results. In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up. Conclusion/interpretation. Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.

  • 48. Borisova, TK
    et al.
    Rosén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Sidorova, EV
    Human monoclonal antibodies to synthetic viral peptides.1999In: Voprosy virusologii, ISSN 0507-4088, Vol. 44, p. 172-174Article in journal (Refereed)
  • 49.
    Brynhildsen, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Dahle, Charlotte
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology.
    Behrbohm Fallsberg, M
    Rundquist, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Hammar, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Attitudes among students and teachers on vertical integration between clinical medicine and basic science within a problem-based undergraduate medical curriculum2002In: Medical teacher, ISSN 0142-159X, E-ISSN 1466-187X, Vol. 24, no 3, p. 286-288Article in journal (Refereed)
    Abstract [en]

    Important elements in the curriculum at the Faculty of Health Sciences in Link÷ping are vertical integration, i.e. integration between the clinical and basic science sections of the curriculum, and horizontal integration between different subject areas. Integration throughout the whole curriculum is time-consuming for both teachers and students and hard work is required for planning, organization and execution. The aim was to assess the importance of vertical and horizontal integration in an undergraduate medical curriculum, according to opinions among students and teachers. In a questionnaire 102 faculty teachers and 106 students were asked about the importance of 14 different components of the undergraduate medical curriculum including vertical and horizontal integration. They were asked to assign between one and six points to each component (6 points = extremely important for the quality of the curriculum, 1 point = unimportant). Students as well as teachers appreciated highly both forms of integration. Students scored horizontal integration slightly but significantly higher than the teachers (median 6 vs 5 points, p=0.009, Mann-Whitney U-test), whereas teachers scored vertical integration higher than students (6 vs 5, p=0.019, Mann-Whitney U-test). Both students and teachers considered horizontal and vertical integration to be highly important components of the undergraduate medical programme. We believe both kinds of integration support problem-based learning and stimulate deep and lifelong learning and suggest that integration should always be considered deeply when a new curriculum is planned for undergraduate medical education.

  • 50.
    Canedo, P.
    et al.
    University of Porto, Portugal.
    Thorselius, M.
    Uppsala University.
    Thunberg, U.
    Uppsala University.
    Sällström, J.
    Uppsala University.
    Sundström, C.
    Uppsala University.
    Rosén, Anders
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Söderberg, O.
    University of Porto, Portugal.
    A Follicular Dendritic Cell Line Promotes Somatic Hypermutations in Ramos cells In Vitro2009In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 69, no 1, p. 70-71Article in journal (Other academic)
1234567 1 - 50 of 354
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