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  • 201. Bruening-Wright, Andrew
    et al.
    Elinder, Fredrik
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Larsson, H Peter
    Kinetic relationship between the voltage sensor and the activation gate in spHCN channels2007In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 130, no 1, p. 71-81Article in journal (Refereed)
    Abstract [en]

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarizations that cause an inward movement of the positive charges in the fourth transmembrane domain (S4), which triggers channel opening. The mechanism of how the motion of S4 charges triggers channel opening is unknown. Here, we used voltage clamp fluorometry (VCF) to detect S4 conformational changes and to correlate these to the different activation steps in spHCN channels. We show that S4 undergoes two distinct conformational changes during voltage activation. Analysis of the fluorescence signals suggests that the N-terminal region of S4 undergoes conformational changes during a previously characterized mode shift in HCN channel voltage dependence, while a more C-terminal region undergoes an additional conformational change during gating charge movements. We fit our fluorescence and ionic current data to a previously proposed 10-state allosteric model for HCN channels. Our results are not compatible with a fast S4 motion and rate-limiting channel opening. Instead, our data and modeling suggest that spHCN channels open after only two S4s have moved and that S4 motion is rate limiting during voltage activation of spHCN channels. © The Rockefeller University Press.

  • 202.
    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.

  • 203. Bu, H
    et al.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Holmdahl-Källén, K
    Sun, Xiao-Feng
    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.
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Significance of glutathione S-transferases M1, T1 and P1 polymorphisms in Swedish melanoma patients.2007In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 17, no 4, p. 859-864Article in journal (Refereed)
    Abstract [en]

    Polymorphisms of GSTM1, GSTT1 and GSTP1 were examined in melanoma patients and tumor-free individuals. Relationships between the polymorphisms and tumor characteristics and pigment phenotypes of the patients were analyzed. There was no significant difference in GSTM1 null and GSTT1 null genotypes nor GSTP1 GG genotype between melanoma patients and controls. In melanoma patients, these polymorphisms were not correlated with early or later onset of melanomas or gender of the patients. Frequency of GSTM1 null genotype was higher in patients with melanoma >2.5 mm than in those with tumors <1.0 mm, and higher frequency was found in nodular melanoma than in the other tumor types. GSTP1 GG genotype was more often found in the patients with brown and mixed eye color or brown and black hair than those with blue and green eyes or blond hair. It is unlikely that polymorphisms of GSTM1, GSTT1 and GSTP1 are general risk factors for melanoma in the Swedish population. GSTM1 null genotype was correlated with Breslow thickness and tumor type, which might serve as an additional biomarker for a rapid tumor progression. GSTP1 GG increases risk for melanoma in the subgroup of individuals with dark eyes or hair.

  • 204.
    Bu, Huajie
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Holmdahl-Källenand, Katarina
    Zhang, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Importance of polymorphisms at NF-κB1 and NF-κBIα genes in melanoma risk, clinicopathological features and tumor progression in Swedish melanoma patients2007In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 133, no 11, p. 859-866Article in journal (Refereed)
    Abstract [en]

    In this study, functional polymorphisms of NF-κB1 and NF-κBIα genes were examined in 185 melanoma patients and 438 tumor-free individuals. Associations of the polymorphisms with melanoma risk, age and pigment phenotypes of the patients and clinico-pathological tumor characteristics were analyzed. DNAs were isolated from mononuclear cells of venous blood. Polymorphisms of the genes were genotyped by a PCR-RFLP technique, and transcription level of NF-κBIα was examined by a quantitative real-time reverse transcription PCR. Results showed that both ATTG insertion polymorphism of NF-κB1 and A to G polymorphism of NF-κBIα genes were correlated with melanoma risk, especially, in a combination of ATTG2/ATTGT2 and GG. NF-κB1 ATTG2/ATTG2 and NF-κBIα GG genotypes were associated with male gender and age > 65 years (at diagnosis). Patients with ATTG1/ATTG1 genotype had thinner tumors and lower Clark levels at diagnosis. Frequency of ATTG1/ATTG1 genotype was higher in patients with melanomas on intermittently sun-exposed pattern of the body and NF-κBIα GG was more frequent in the patients with melanomas at rarely exposed sites. There were no differences in the gene transcription level between patients with different NF-κBIα genotypes. These data suggest that NF-κB1 and NF-κBIα genes might be susceptible genes for melanoma risk and functional polymorphisms of these genes might be biological predictors for melanoma progression.

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  • 205. Burnett, Robert W
    et al.
    D'Orazio, Paul
    Fogh-Andersen, Niels
    Kuwa, Katsuhiko
    Külpmann, Wolf
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lewnstam, Andrzej
    Maas, Anton
    Mager, Gerhard
    Spichiger-Keller, Ursula
    IFCC recommendation on reporting results for blood glucose.2001In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 307, p. 205-209Article in journal (Refereed)
  • 206. Bäckman, C
    et al.
    Orwelius, Lotti
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nursing Science.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Nordlund, P
    Simonsson, E
    Walther, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Do ICU-diaries influence health related quality of life after critical illness?2007In: in Intensive Care Medicine(ISSN 0342-4642), vol 33, 2007, Vol. 33, p. 13-13Conference paper (Refereed)
  • 207.
    Bäckman, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Bergh, Ann-Charlotte
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Lagerdahl, I
    Rydberg, B
    Sundström, C
    Tobin, G
    Rosenquist, R
    Linderholm, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Rosén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Thioredoxin, produced by stromal cells retrieved from the lymph node microenvironment, rescues chronic lymphocytic leukemia cells from apoptosis in vitro2007In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 92, no 11, p. 1495-1504Article in journal (Refereed)
    Abstract [en]

    Background and Objectives: The redox-regulatory protein thioredoxin has several functions including transcriptional regulation, and antioxidant, cytokine, and chemokine activities. We have previously shown that extracellular thioredoxin protects B-cell chronic lymphocytic leukemia (CLL) cells from apoptosis in vitro. In this study we were interested to determine whether thioredoxin is produced by cells surrounding the CLL cells in the in vivo microenvironment and whether this cell-derived thioredoxin has any leukemia growth-promoting effect in vitro. Design and Methods: Lymph nodes from CLL patients (n=25) were analyzed for thioredoxin expression by immunohistology. Stromal cells purified from the lymph nodes were analyzed for thioredoxin secretion at the single cell level using an ELIspot assay. The survival effect of the stromal-derived thioredoxin was tested by co-culturing stromal- and CLL cells with and without Fab-fragments of an anti-thioredoxin antibody. Results: The results indicated that the thioredoxin production correlated with the amount of proliferating cells and was mainly localized to the proliferation centers (pseudofollicles) in the CLL lymph nodes. The leukemia cells per se showed minimal thioredoxin levels, in contrast, stromal cells strongly expressed thioredoxin. Purified primary stromal cells, which secreted extracellular thioredoxin, significantly protected the CLL cells from undergoing apoptosis in 72 h co-cultures. Interestingly, this anti-apoptotic effect could be abrogated by addition of Fab-fragments of an anti- thioredoxin antibody. Interpretation and Conclusions: In conclusion, we have shown that stromal cells in the lymph node microenvironment produce thioredoxin and that the thioredoxin production is localized to the proliferation centers of the CLL lymph nodes. In addition, thioredoxin produced by purified stromal cells rescued CLL cells from apoptosis in vitro. ©2007 Ferrata Storti Foundation.

  • 208. Bülow, B
    et al.
    Jansson, S
    Juhlin, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Steen, L
    Thorén, M
    Wahrenberg, H
    Valdemarsson, S
    Wangberg, B
    Ahrén, B
    Adrenal incidentaloma - Follow up results from a Swedish prospective study2006In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 154, no 3, p. 419-423Article in journal (Refereed)
    Abstract [en]

    Objectives: To examine the risk of developing adrenal carcinomas and clinically overt hypersecreting tumours during short-term follow-up in patients with adrenal incidentalomas. Design: 229 (98 males and 131 females) patients with adrenal incidentalomas were investigated in a prospective follow-up study (median time 25 months, range 3-108 months). The patients were registered between January 1996 and July 2001 and followed until December 2004. Twenty-seven Swedish hospitals contributed with follow-up results. Methods: Diagnostic procedures were undertaken according to a protocol including reinvestigation with computed tomography scans after 3-6 months, 15-18 months and 27-30 months, as well as hormonal evaluation at baseline and after 27-30 months of follow-up. Operation was recommended when the incidentaloma size increased or if there was a suspicion of a hypersecreting tumour. Results: The median age at diagnosis of the 229 patients included in the follow-up study was 64 years (range 28-84 years) and the median size of the adrenal incidentalomas when discovered was 2.5 cm (range 1-8 cm). During the follow-up period, an increase in incidentaloma size of ≥0.5 cm was reported in 17 (7.4%) and of ≥ 1.0 cm was reported in 12 (5.2%) of the 229 patients. A decrease in size was seen in 12 patients (5.2%). A hypersecreting tumour was found in 2% of the hormonally investigated patients: cushing's syndrome (n = 2) and phaeochromocytoma (n = 1). Eleven patients underwent adrenalectomy, but no cases of primary adrenal malignancy were observed. Conclusions: Patients with adrenal incidentaloma had a low risk of developing malignancy or hormonal hypersecretion during a short-term follow-up period. © 2006 Society of the European Journal of Endocrinology.

  • 209.
    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)
  • 210.
    Cao, Jun
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Characterization of antibodies against Helicobacter pylori1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    H. pylori is associated with the development of peptic ulcer, gastritis, and gastric cancer. Eradication of H. pylori by antibiotic treatment gives a healing of peptic ulcer and gastritis. However, due to drug resistance, there is a great need to explore alternative ways to eliminate bacterial infections.

    The goals of the present study were to characterize MAbs against surface components of H. pylori, and to investigate the functions of the bacterial surface components.

    Murine MAbs against surface components of H. pylori were produced by immunization of mice followed by hybridoma formation. One of the MAbs of the IgG1 subclass, was specific for both the spiral and coccoid forms of H. pylori. It reacted with a 28 kDa protein that was present in all the 5 strains of H. pylori tested. The MAb based indirect immunofluorescence microscopy on formalinfixed antral and corpus biopsy specimens from H. pylori associated gastritis patients showed that 9 of 9 antral and 5 of 6 corpus specimens harbored the coccoid form of H. pylori.

    An ScFv-phage which was derived from an M13 phage and mRNA of hybridomas secreting H. pylori MAbs, reacted with a 30 kDa H. pylori surface antigen. By means of immunofluorescence microscopy the phage was shown to bind to both the spiral and coccoid forms of the bacterium. In vitro the recombinant phage exhibited a bacteriocidal effect. When H. pylori was pretreated with the phage before oral inoculation of mice, the colonization of the mouse stomachs by the bacterium was significantly reduced. The parental MAbs were of the IgG1 subclass. The antigen was identified as a urease associated 30 kDa protein. The MAb decreased viability of the spiral form in broth culture, and reduced intracellular ATP in both spiral and coccoid forms of H. pylori.

    One MAb, 5D6 of the IgG2a subclass, was specific to a 56 kDa H. pylori protein. Immunofluorescence microscopy showed that this protein was located on the surface of both the spiral and coccoid forms of H. pylori. The MAb also bound to cells of the basal third of the oxyntic mucosa of rat stomachs and these cells were identified as gastric ECL cells. Sera of H. pylori-positive patients were investigated for ECL cell (auto)antibodies by means of ELISA using purified rat ECL cells as antigen. Ten (25%) of 40 sera from patients with atrophic corpus predominant gastritis scored positive; 2 (8%) of 26 sera from the patients with duodenal ulcer scored positive; only 1 serum (6%) from 16 healthy subjects was slightly positive. Four positive clones were obtained from a DNA hybridization of H. pylori and human gastric mucosa.

    The present results show that the MAb based immunochemistry provides a rapid and specific detection of both the spiral and coccoid forms. Binding of a urease associated 30 kDa protein by an ScFv-phage, or by its parental MAbs, decreased the viability of H. pylori. The protein may be considered as a candidate for a future vaccine. An antigenic mimicry which was found in surface of H. pylori and gastric ECL cells suggests a pathogenic role in gastritis.

  • 211.
    Cao, Jun
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Sun, Yi-Qian
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Berglindh, Thomas
    Mellgård, Björn
    Li, Zhao-qi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Mårdh, Bibbi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Helicobacter pylori-antigen-binding fragments expressed on the filamentous M13 phage prevent bacterial growth2000In: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1474, no 1, p. 107-113Article in journal (Refereed)
    Abstract [en]

    Colonization of the human stomach by Helicobacter pylori is associated with the development of gastritis, duodenal ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. H. pylori-antigen-binding single-chain variable fragments (ScFv) were derived from murine hybridomas producing monoclonal antibodies and expressed as a g3p-fusion protein on a filamentous M13 phage. The recombinant ScFv-phage reacted specifically with a 30-kDa monomeric protein of a H. pylori surface antigen preparation and by means of immunofluorescence microscopy the phage was shown to bind to both the spiral and coccoid forms of the bacterium. In vitro, the recombinant phage exhibited a bacteriocidal effect and inhibited specifically the growth of all the six strains of H. pylori tested. When H. pylori was pretreated with the phage 10 min before oral inoculation of mice, the colonization of the mouse stomachs by the bacterium was significantly reduced (P<0.01). The results suggest that genetic engineering may be used to generate therapy-effective phages.

  • 212.
    Carlander, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Johansson, Kenth
    Lasarettet Västervik.
    Lindström, Sivert
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Keita, Åsa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Jiang, Chonghe
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Nordborg, C
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Comparison of experimental nerve injury caused by ultrasonically activated scalpel and electrosurgery2005In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 92, no 6, p. 772-777Article in journal (Refereed)
    Abstract [en]

    Background: Iatrogenic nerve injury caused by heat from dissection instruments is a significant problem in many areas of surgery. The aim of the present study was to compare the risk of nerve injury for three different dissection instruments: monopolar and bipolar electrosurgery (ES) and an ultrasonically activated (US) instrument. Methods: The biceps femoris muscle was cut in a standard manner just adjacent to the sciatic nerve using monopolar ES, bipolar ES or US shears. A total of 73 functional experiments were conducted in which the nerve was isolated, divided proximally, and stimulated supramaximally in 37 anaesthetized rats. The electromyographic (EMG) potential was recorded distally before and after each experiment. Nerve dysfunction was defined as more than 10 per cent loss of the evoked EMG potential. Fifty-nine nerves were examined histologically after dissection with the different instruments. The extent of heat damage was determined in four nerves that were divided with ES bipolar scissors and five that were divided with US shears. Results: Reduction in the EMG potential was significantly more frequent in the monopolar ES group than in the US group. Morphological examination also showed significantly less nerve damage in the US group. Conclusion: US instruments may be safer than ES for dissection close to nerves. Copyright © 2005 British Journal of Surgery Society Ltd.

  • 213.
    Carlsson, Margaretha S.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Department of Biomedicine and Surgery, Hematology. Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
    Pharmacokinetics of 2-mercaptopropionylglycine (Tiopronin) in man1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    2-Mercaptopropionylglycine (2-MPG, tiopronin) has been used successfully in the treatment of cystinuria despite the lack of knowledge of its pharmacokinetics. Therefore methods based on high-performance liquid chromatography and fluorometric detection were developed for quantitative analysis. The total, non-protein-bound, and free (thiolic) tiopronin were measured in plasma using this method.

    The phannacokinetic disposition of tiopronin in plasma after intravenous administration was best described by a three exponential function. Plasma concentration time-curves of total tiopronin exhibited a rapid distribution phase, a B-phase corresponding to renal excretion, and a long terminal elimination phase. The latter was the result of strong disulphide binding of tiopronin to proteins. The non-protein-bound tiopronin was eliminated faster judging by its early appearance in urine. Mean bioavailability was 63 % in healthy volunteers with great interindividual variability (range 33-91%).

    Multiple dosing studies gave similar pharrnacokinetic parameters as for single dose studies and studies on patients with renal impaitment elucidated the renal clearance of the drug. In vitro studies showed a slow dissolution of the drug dosage form employed. A metabolite, 2-mercaptopropionic acid, was identified and its pharmacokinetics was investigated. The mechanism of action of the drug is discussed based on the results of measuring free tiopronin in plasma.

  • 214. Carlsson, Maria
    et al.
    Strang, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Palliative mediicin. Östergötlands Läns Landsting, ViN, LAH Linnea.
    Bjurström, Christina
    Treatment modality affects long-term quality of life in gyaecological cancer.2000In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 20, no 1B, p. 563-568Article in journal (Refereed)
    Abstract [en]

    In order to survey the side effects after cancer treatment, quality of life data were collected from females in clinical remission, Materials and Methods: The study was cross-sectional, every patient that visited the outpatient clinic during a period of thr ee months was asked to anonymously complete the EORTC QLQ-C30 questionnaire and five additional specific questions related to gynaecological cancel: Results: In total, 235 patients (90%) returned the questionnaire In general, both the levels of functioning and symptomatology were time-dependent. Patients with short treatment-free intervals reported more problems than the others. When wing treatment modality as an independent variable in the statistical calculations, a treatment-related effect on functioning and symptomatology was demonstrated (p < 0.05 to p < 0.001). Patients previously treated with chemotherapy had poorer role- and cognitive functioning and mole problems with fatigue, nausea, vomiting, dyspnoea, constipation and financial problems, compared with those not treated with chemotherapy (p < 0.05 to p < 0.01). Those patients who had been treated with external radiotherapy and/or brachytherapy had significantly more problems with flatulence and diarrhoea (p < 0.05 to p < 0.001). In conclusion, patients who underwent treatment for gl gynaecological cancer reported long-term side effects also many years after finishing treatment. The problems where related to treatment modality which should be considered, especially when planning adjuvant treatment.

  • 215.
    Carlsson, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Palliative mediicin.
    Strang, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Palliative mediicin. Östergötlands Läns Landsting, ViN, LAH Linnea.
    Nygren, Ulla
    Qualitative analysis of the questions raised by patients with gynecologic cancers and their relatives in an educational support group1999In: Journal of Cancer Education, ISSN 0885-8195, E-ISSN 1543-0154, Vol. 14, p. 41-46Article in journal (Refereed)
  • 216. Carlsson, R.
    et al.
    Dent, J.
    Bolling-Sternevald, E.
    Linköping University, Department of Biomedicine and Surgery.
    Johnsson, F.
    Ljungard, O.
    Lauritsen, K.
    Riley, S.
    Lundell, L.
    The usefulness of a structured questionnaire in the assessment of symptomatic gastroesophageal reflux disease1998In: Scandinavian journal of gastroenterology, ISSN 0036-5521, Vol. 33, no 10, p. 1023-1029Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The diagnosis of gastroesophageal reflux disease (GERD) rests primarily on recognition of symptom patterns that are classical for reflux disease, but little attention has been paid to the use of a formal questionnaire for identifying such symptom patterns. METHODS: A self-administered questionnaire was developed which has seven items that focus on the nature of the symptoms and the precipitating, exacerbating, and relieving factors. The diagnostic validity of the questionnaire was tested against endoscopy and 24-h pH monitoring. A further evaluation was undertaken in patients with symptoms suggestive of GERD and in patients with non-ulcer dyspepsia, to identify factors that might predict symptom relief during treatment with omeprazole. RESULTS: When endoscopic esophageal mucosal breaks and 24-h pH data were used as criteria for the diagnosis of GERD, the questionnaire had a sensitivity of 92% but a very low specificity of 19%. Symptom relief during treatment with omeprazole was predicted by the presence of heartburn, described as 'a burning feeling rising from the stomach or lower chest up towards the neck' (P = 0.004), and 'relief from antacids' (P = 0.02). In non-ulcer dyspepsia a positive response to omeprazole was confined to the subgroup of patients who identified their main discomfort as heartburn as described above. CONCLUSION: The present questionnaire using descriptive language usefully identified heartburn in patients presenting with upper abdominal symptoms, and this symptom predicted symptom resolution during treatment with omeprazole.

  • 217.
    Carlstedt, Thomas
    et al.
    Royal National Orthopaedic Hospital.
    Hultgren, Tomas
    Karolinska Institute.
    Nyman, Torbjörn
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns . Linköping University, Faculty of Health Sciences.
    Hansson, Thomas
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Cortical activity and hand function restoration in a patient after spinal cord surgery2009In: NATURE REVIEWS NEUROLOGY, ISSN 1759-4758, Vol. 5, no 10, p. 571-574Article in journal (Refereed)
    Abstract [en]

    Background. Following a motorcycle accident, a 9-year-old boy experienced a complete right-sided ( dominant) arm and hand paralysis with total sensory loss, Horner syndrome and severe constant pain. This study assessed the long-term outcome of spinal cord surgery undertaken on the patient, focusing on the restored hand function and related cortical activity. The study follows on from previous reports on the same patient. Investigations. Clinical functional and electrophysiological examinations. Functional MRI of cortical activity. Diagnosis. Complete brachial plexus (C5-T1) avulsion from the spinal cord. Management. Spinal cord surgery to restore motor trajectories.

  • 218.
    Carstensen, John
    et al.
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    Billström, R
    Universitetssjukhuset i Lund.
    Gruber, A
    Karolinska universitetssjukhuset.
    Hellström-Lindberg, E
    Karolinska universitetssjukhuset.
    Höglund, M
    Akademiska sjukhuset i Uppsala.
    Karlsson, Karin
    Hematologi Lunds universitet.
    Stockelberg, D
    Sahlgrenska universitetssjukhuset.
    Wahlin, A
    Norrlands universitetssjukhus.
    Åström, M
    Universitetssjukhuset i Örebro.
    Arnesson, C
    Universitetssjukhuset i Lund.
    Brunell-Abrahamsson, U
    Akademiska sjukhuset i Uppsala.
    Fredriksson, E
    Karolinska universitetssjukhuset.
    Holmberg, E
    Sahlgrenska universitetssjukhuset.
    Wiklund, F
    Norrlands universitetssjukhus.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Nordenskjöld, Kerstin
    Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival2006In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 20, no 1, p. 42-47Article in journal (Refereed)
    Abstract [en]

    Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention (RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70 -79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region (range 36 -76%) and the two-year overall survival, with no censored observations (6 -21%) (χ2 for trend=11.3, P<0.001, r2=0.86, P<0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates (P=0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70 -79 years was similar between the regions. Survival of 70 -79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction. © 2006 Nature Publishing Group All rights reserved.

  • 219. Ceder, G
    et al.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Concentrations of unconjugated morphine, codeine, and 6-acetyl morphine in urine specimens from suspected drugged drivers.2002In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 47, p. 366-368Article in journal (Refereed)
    Abstract [en]

    Concentrations of unconjugated morphine, codeine and 6-acetylmorphine (6-AM), the specific metabolite of heroin, were determined in urine specimens from 339 individuals apprehended for driving under the influence of drugs (DUID) in Sweden. After an initial screening analysis by immunoassay for 5-classes of abused drugs (opiates, cannabinoids, amphetamine analogs, cocaine metabolite and benzodiazepines), all positive specimens were verified by more specific methods. Opiates and other illicit drugs were analyzed by isotope-dilution gas chromatography-mass spectrometry (GC-MS). The limits of quantitation for morphine, codeine and 6-AM in urine were 20 ng/mL Calibration plots included an upper concentration limit of 1000 ng/mL for each opiate. We identified the heroin metabolite 6-AM in 212 urine specimens (62%) at concentrations ranging from 20 ng/mL to > 1000 ng/mL The concentration of 6-AM exceeded 1000 ng/mL in 79 cases (37%) and 31 cases (15%) were between 20 and 99 ng/mL. When 6-AM was present in urine the concentration of morphine was above 1000 ng/mL in 196 cases (92%). The concentrations of codeine in these same urine specimens were more evenly distributed with 35% being above 1000 ng/mL and 21% below 100 ng/mL. These results give a clear picture of the concentrations of unconjugated morphine, codeine and 6-acetylmorphine that can be expected in opiate-positive urine specimens from individuals apprehended for DUID after taking heroin.

  • 220. Ceder, Gunnel
    et al.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Concentration ratios of morphine to codeine in blood of impaired drivers as evidence of heroin use and not medication with codeine2001In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 47, no 11, p. 1980-1984Article in journal (Refereed)
    Abstract [en]

    Background: Both the illicit drug heroin and the prescription drug codeine are metabolized to morphine, which tends to complicate interpretation of opiate-positive samples. We report here the concentrations of morphine and codeine, the morphine/codeine ratios, and 6-acetylmorphine (6-AM) in blood specimens from individuals arrested for driving under the influence of drugs (DUID) in Sweden. The results were compared with positive findings of 6-AM in urine as evidence of heroin intake. Methods: In 339 DUID suspects, both blood and urine specimens were available for toxicologic analysis. In another 882 cases, only blood was available. All specimens were initially analyzed by immunoassay, and the positive results were verified by isotope-dilution gas chromatography-mass spectrometry. In routine casework, the limits of quantification (LOQs) for unconjugated opiates were 5 ng/g for blood and 20 ╡g/L for urine. Results: The median concentration of morphine in blood was 30 ng/g with 2.5 and 97.5 percentiles of 5 and 230 ng/g, respectively (n = 979). This compares with a median codeine concentration of 20 ng/g and 2.5 and 97.5 percentiles of 5 and 592 ng/g, respectively (n = 784). The specific metabolite of heroin, 6-AM, was identified in only 16 of 675 blood specimens (2.3%). This compares with positive findings of 6-AM in 212 of 339 urine samples (62%) from the same population of DUID suspects. When 6-AM was identified in urine, the morphine/codeine ratio in blood was always greater than unity (median, 6.0, range, 1-66). In 18 instances, 6-AM was present in urine, although morphine and codeine were below the LOQ in blood. The morphine/codeine ratio in blood was greater than unity in 85% of DUID cases when urine was not available (n = 506), and the median morphine and codeine concentrations were 70 ng/g and 10 ng/g, respectively. When morphine/codeine ratios in blood were less than unity (n = 76), the median morphine and codeine concentrations were 10 ng/g and 180 ng/g, respectively. Conclusions: Only 2.3% of opiate-positive DUID suspects were verified as heroin users on the basis of positive findings of 6-AM in blood. A much higher proportion (62%) were verified heroin users from 6-AM identified in urine. When urine was not available for analysis, finding a morphine/codeine concentration ratio in blood above unity suggests heroin use and not medication with codeine. This biomarker indicated that 85% of opiate-positive DUID blood samples were from heroin users. ⌐ 2001 American Association for Clinical Chemistry.

  • 221.
    Cederbrant, Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Andersson, C.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Andersson, T.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Marcusson-Ståhl, Maritha
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Hultman, Per
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    IL-10 production in primary PBMC cultures: an in vitro marker for nickel allergy?Manuscript (preprint) (Other academic)
    Abstract [en]

    Nickel (Ni) is one of the most known contact allergens and at present, patch test and clinical history constitute the two cornerstones in the diagnostic procedure. Since the patch test is inherited with in vivo provocation and subjective interpretation of the test result, a non-invasive in vitro method with objective interpretation of the test result has long been searched for. Unfortunately, in vitro diagnosis of Ni- allergy is hampered by the fact that Ni2+ is able to trigger in vitro proliferative responses in lymphocytes from both Ni-allergic and non-allergic subjects. This constitutes a problem when LTT (lymphocyte transformation test), the most frequently used in vitro test as a complement in the diagnosis of contact allergy, is considered for Ni allergy. However, other parameters in the in vitro response might be more useful. In this study, Ni2+-stimulated primary PBMC-cultures derived from Ni-allergic and non-allergic subjects were assessed for IFN-γ, IL-4, IL-10 and IL-17. Also, Ni2+ induced lymphoblasts from such cultures were characterized by their immunophenotype and T-cell receptor Vß-affiliation.

    We found a significantly higher release of IL-10 in Ni2+ treated cultures from allergic than from non-allergic subjects. The Ni2+-induced lymphoblasts from both groups were predominantly CD4+. Two of the allergic patients (n=5) showed a skewing towards TCR-Vß17, a Vß family earlier associated with Ni-allergy. A significant increase in CD134 and CD23 expression indicated that Ni2+ activates B-cells in vitro. In conclusion, IL-10 seems to be a promising marker for Ni-allergy using primary PBMC cultures. Further, flow cytometric screening of Ni2+ induced lymphoblasts can detect expanded TCR-Vß families that may be used for preparation of Ni-specific T cell clones.

  • 222.
    Chaireti, Roza
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Arbring, Kerstin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Olsen, Ole H.
    Novo Nordisk A/S, Novo Nordisk Park, Måløv, Danmark.
    Persson, Egon
    Novo Nordisk A/S, Novo Nordisk Park, Måløv, Danmark.
    Lindahl, Tomas L.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Thrombin generation and levels of factor VII activity measured in the presence of rabbit and human thromboplastins in patients with mild factor VII deficiency – effects of mutations in factor VIIManuscript (preprint) (Other academic)
    Abstract [en]

    Background/Aim: It is known that spontaneous prolonged prothrombin time-international normalized ratio may be caused by deficiency of factor VII (FVII). The activity of FVII in the presence of thromboplastins of different origin is affected by the presence of specific mutations in the F7 gene. The present study aims to evaluate patients with mild FVII deficiency and somewhat discrepant FVII activity depending on the use of human or rabbit thromboplastin in relation to mutations in the FVII gene and markers of thrombin generation.

    Patients and methods: A cohort of 10 patients with mild deficiency of FVII and discrepant FVII activity was investigated. The median ratio of the FVII activity in the presence of human/rabbit thromboplastin was 1.4. All but 1 patient had mild to no bleeding symptoms. A genetic analysis of the F7 gene was performed. Thrombin generation was measured by the calibrated automated thrombogram in platelet poor plasma in the presence of human recombinant and different dilutions of rabbit thromboplastin and compared with thrombin generation in healthy controls (n=12). Thrombin generation was measured in 9 patients as 1 was treated with warfarin at the time of the blood sampling.

    Results: Six previously described mutations were found. Two of those (FVII Padua and FVII Shinjo) are known to affect the results for FVII activity dependent on the species origin of the thromboplastin. Nine out of 10 patients had one mutation in common (Arg353Gln), which however does not affect the binding site of FVII to tissue factor. Lagtime and ttpeak increased with decreasing concentrations of thromboplastin and total and maximum thrombin concentrations increased with increasing thromboplastin concentrations in the patients with FVII deficiency. ETP in patients with FVII deficiency was 86% of ETP in controls.

    Discussion: The Arg353Gln mutation was very common, however it does not appear to affect the reactivity towards thromboplastins of different origins. Although ETP was higher in the healthy controls, thrombin generation in FVII deficient patients was enough to sustain normal haemostasis. The expected thrombin generation patterns with increasing thromboplastin concentrations were confirmed for the patients in this study.

  • 223. Chen, H
    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.
    Dong, LQ
    Cong, L
    Li, Y
    Liu, F
    Insulin-stimulated activation of phosphoinositide-dependent Kinase-1 (PDK1): potential role in translocation of CLUT4 in rat adipose cells.2001In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 30, p. 11851-11859Article in journal (Refereed)
  • 224.
    Chen, Yun
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Smooth muscle hypertrophy and the IGF-system1996Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Insulin-like growth factor-! (IGF-I) has both metabolic and mitogenic effects on smooth muscle cells (SMCs). The effects of IGF-I are modified by a group of binding proteins (IGFBPs). The present study was devoted to smooth muscle hypertrophy and the IGF-system in smooth muscle under different conditions.

    In urinary bladder, smooth muscle hypertrophy, initiated by partial outletobstruction, was associated with a transient increase in IGF-I mRNA, and pronounced, sustained increases oflGFBP-2 and IGFBP-4 mRNA, as well as increased protein contents of IGF-I and IGFBP-2. Regression of smooth muscle hypertrophy was associated with normalization of levels ofiGF-I, IGFBP-2 and IGFBP-4 mRNA. Expression of the IGF-I receptor did not change significantly.

    In portal vein, IGF-I mRNA and IGF-1 immunoreactivity were increased inhypertrophy induced by partialligation of the portal vein.

    Abdominal coarctation caused a rapid hypertensive response accompanied by an increased wet weight of aortic media. This was coincident with a progressive increase in aortic IGFBP-2 mRNA, about 10-fold after 14 days.

    The levels of IGFBP-4 mRNA in different muscle tissues and liver were decreased by diabetes and fasting, while IGFBP-2 mRNA was regulated in an organspecific 1nanner: with a sustained increase in liver and a decrease in aortic smooth muscle.

    Smooth muscle hypertrophy also occured in the urinary bladder of diabetic rats. DNA synthesis was increased and peaked at 2 days after induction of diabetes. DNA content per bladder wet weight was decreased by 7 days. Initially there was no changes in IGF-I mRNA, while IGFBP-2 mRNA and protein in the bladders were increased and peaked by 7 days. IGFBP-4 mRNA increased only on day 7. The changes of mRNA in bladder differed from that in liver and aorta, and suggested an early effect of stretching of the bladder due to diuresis, and later a contribution by the diabetic state.

    In cultured vascular SMCs, mechanical strain stimulated protein synthesis, but had little effect on DNA synthesis. However, mechanical strain potentiated the actions of IG:F'-1 and serum on both protein- and DNA synthesis, and influenced the effects of IGFBP-2.

    In conclusion, development of smooth muscle hypertrophy is associated with specific changes in IGF-I, IGFBP-2 and IGFBP-4, suggesting that the IGF-system may play a role in this process.

  • 225.
    Chen, Yun
    et al.
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden, Department of Physiology, University of Gothenburg, Box 432, SE 405 30 Gothenburg, Sweden.
    Lasaitiene, Daina
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Gabrielsson, Britt G.
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlsson, Lena M. S.
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Billig, Håkan
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Carlsson, Björn
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Marcussen, Niels
    Institute of Pathology, Aarhus Kommunehospital, Aarhus, Denmark.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, KC - Kirurgi- och onkologicentrum, Onkologiska kliniken.
    Friberg, Peter
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Neonatal Losartan Treatment Suppresses Renal Expression of Molecules Involved in Cell-Cell and Cell-Matrix Interactions2004In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 15, no 5, p. 1232-1243Article in journal (Refereed)
    Abstract [en]

    Lack of neonatal angiotensin II type I receptor (AT1) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT 1 receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, ~30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, a-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin a6 and caused relocalization of integrins a6 and a3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT1 receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and a-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.

  • 226. Chernyshova, IN
    et al.
    Borisova, TK
    Emelyanzeva, JA
    Sidorova, EV
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Role of different lymphocyte subpopulations in the formation of non-specific immunoglobulins induced by antigen injection.1999In: Human Antibodies, ISSN 1093-2607, E-ISSN 1875-869X, Vol. 9, p. 107-110Article in journal (Refereed)
  • 227.
    Choremi-Papadopoulou, Helen
    et al.
    Immunologu Department Laiko General Hospital.
    Faure, Gilbert C.
    Laboratorie dImmunologie Université Henri Poincaré.
    Grunnet, Niels
    Department of Clinical Immunology Aarhus University Hospital.
    Madden, Michael
    Dept. Haematology Mercy University Hospital.
    Malenica, Branko
    Department of Immunology University Center Zagreb.
    Misbah, Siraj A
    Department of Clinical Immunology Oxford Radcliffe Hospitals.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Zlabinger, Gerhard J
    Institute of Immunology Medical University of Vienna.
    Position statement: Training programme in immunology of the European Board of UEMS Medical Biopathology [2]2005In: Immunology Letters, ISSN 0165-2478, E-ISSN 1879-0542, Vol. 96, no 2, p. 305-310Article in journal (Refereed)
  • 228.
    Chu, Ming
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    The role of endogenous hypercholecystokininemia and hypergastrinemia in growth and carcinogenesis of the exocrine pancreas1996Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The gut hormones cholecystokinin (CCK) and gastrin are phylogeneticallyand structurally related. Under normal conditions, CCK regulates growth of the exocrine pancreas and gastrin growth of the oxyntic mucosa of the stomach. The effects of chronically increased endogenous secretion ofCCK or gastrin on pancreatic growth and carcinogenesis are not fully investigated. This thesis deals with such studies in rats and hamsters, using pancreaticobiliary diversion (PBD) to accomplish endogenous hypercholecystokininemia and gastric fundectomy to accomplish endogenous hypergastrinemia.

    PBD caused an immediate and persistent increase in the plasma CCKconcentration without affecting the plasma gastrin concentration. In hamsters, PBD induced an initial hyperplasia (increased [3H]-thymidine labeling index) of acinar cells followed by a persistent hypertrophy (increased weight, protein content, and DNA content) of the pancreas. No such changes were found in PBD operated hamsters receiving a CCK-A receptor antagonist. Longterm (14 months) PBD in rats lead to an increased fraction of aneuploid cells (DNA flow cytometry) in pancreatic tissue, and development of putative pre-neoplastic lesions (PPL) (acidophilic atypical acinar cell foci) and adenoma of the pancreas. No PPL or neoplasia were observed after longterm ( 8 months) PBD in hamsters. When rats were given a pancreatic carcinogen (azaserine), addition of PBD caused an increase in the fraction of aneuploid cells and in the volume fraction and cellular proliferation ( [3H]-thymidine labeling index) of the PPL. When hamsters were given a panceatic carcinogen (N-nitrosobis(2-oxopropyl)amine) (BOP), addition of PBD caused an increase in the incidence of PPL (ductal complexes) and ductal carcinoma in situ was observed. Furthermore, PBD caused an increase in the proliferative activity of the PPL. No increased proliferation in the PPL was seen in PBD operated animals receiving a CCK-A receptor antagonist.

    Gastric fundectomy caused an immediate and persistent increase in theplasma gastrin concentration without affecting the plasma CCK concentration. In hamsters, fundectomy induced an initial hyperplasia of acinar, ductal, and centroacinar cells followed by a persistent hypertrophy of the pancreas. No such changes were found in fundectomized animals receiving a CCK-B/gastrin receptor antagonist. Longterm (14 months) fundectomy in rats lead to an increase in the fraction of aneuploid cells in pancreatic tissue and development of PPL, but not neoplasia. No PPL or neoplasia were observed after long-standing ( 8 months) fundectomy in hamsters. When rats were given a pancreatic carcinogen (azaserine), addition of fundectomy lead to an increase in the fraction of aneuploid cells and an increase in the volumefraction, but not the proliferative activity, of the PPL. When hamsters weregiven a panceatic carcinogen (BOP), addition of fundectomy did not cause any significant change in the incidence or proliferative activity of PPL, and no neoplasia was observed.

    In conclusion, PBD induced persistent hypercholecystokininemia andfundectomy persistent hypergastrinemia, both of which induced exocrine tissue hyperplasia leading to persistent hypertrophy of the pancreas in rats and hamsters. The effects of PBD and fundectomy seemed to be mediated by CCK and gastrin, since they were blocked by simultaneous administration of a specific CCK-A and CCK-B/gastrin receptor antagonist, respectively. In longterm studies, both procedures caused development of PPL of the pancreas in rats but not in hamsters. In both rats and hamsters treated with a pancreatic carcinogen, addition of PBD enhanced the development of PPL. In rats, but not in hamsters, addition of fundectomy to carcinogen treatment also enhanced the development of PPL. Overall, the trophic as well as the promotive effects were significantly more pronounced after PBD than after fundectomy. In both rats and hamsters, pancreatic neoplasia was observed after PBD, but not after fundectomy.

  • 229. Clancy, N.
    et al.
    Leahy, MJ.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Non-invasive assessment of the mechanical properties of human skin - investigation of effective age using an optical method2006In: Royal Academy of Medicine in Ireland, Section of Biomedical Sciences, University of Limerick, Summer Meeting,2006, 2006Conference paper (Refereed)
  • 230.
    Clancy, Neil T.
    et al.
    Department of Physics, University of Limerick, Ireland.
    Leahy, Martin J.
    Department of Physics, University of Limerick, Ireland.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Analysis of skin recovery from mechanical indentation using diffuse lighting and digital imaging2007In: Diffuse Optical Imaging of Tissue / [ed] Brian W. Pogue; Rinaldo Cubeddu, SPIE - International Society for Optical Engineering, 2007, p. 66291G-1-66291G-10Conference paper (Other academic)
    Abstract [en]

    Skin behaves as a viscoelastic material, having mechanical properties composed of elastic and fluid components. Upon indentation, the fibres are stretched and fluid displaced from the compressed region. The rate of recovery from this imprint is therefore dependent on the hydration and elasticity of the skin. A reliable measurement could be applied to the assessment of clinical conditions such as oedema, rare genetic disorders such as cutis laxa  and the evaluation of the 'effective age' of skin in vivo . This paper describes a new approach to the non-invasive indentation technique and a novel method of analysis. A method is proposed that tracks the skin's recovery optically from an initial strain made using a mechanical indentor, diffuse side-lighting and a CCD video-capture device. Using the blue colour plane of the image it is possible to examine the surface topography only, and track the decay of the imprint over time. Two algorithms are discussed for the extraction of information on the skin's displacement and are analysed in terms of reliability and reproducibility.

  • 231.
    Clancy, Neil T.
    et al.
    Department of Physics, University of Limerick, Ireland.
    Leahy, Martin J.
    Department of Physics, University of Limerick, Ireland.
    Nilsson, Gert E.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Analysis of skin recovery from mechanical indentation using diffuse lighting and digital imaging. in Diffuse Optical Imaging of Tissue.2007In: Proceedings of SPIE - Diffuse Optical Imaging of Tissue / [ed] Brian W. Pogue, Rinaldo Cubeddu, Bellingham, WA, United States: SPIE - International Society for Optical Engineering, 2007, p. 66291G-1-66291G-10Conference paper (Refereed)
    Abstract [en]

    Skin behaves as a viscoelastic material, having mechanical properties composed of elastic and fluid components. Upon indentation, the fibres are stretched and fluid displaced from the compressed region. The rate of recovery from this imprint is therefore dependent on the hydration and elasticity of the skin. A reliable measurement could be applied to the assessment of clinical conditions such as oedema, rare genetic disorders such as cutis laxa and the evaluation of the 'effective age' of skin in vivo . This paper describes a new approach to the non-invasive indentation technique and a novel method of analysis. A method is proposed that tracks the skin's recovery optically from an initial strain made using a mechanical indentor, diffuse side-lighting and a CCD video-capture device. Using the blue colour plane of the image it is possible to examine the surface topography only, and track the decay of the imprint over time. Two algorithms are discussed for the extraction of information on the skin's displacement and are analysed in terms of reliability and reproducibility.

  • 232. Clancy, NT.
    et al.
    Leahy, MJ.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Analysis of mechanical imprints in human skin using an optical technique. in Fission Impossible?2007In: IOPI Spring Weekend Meeting,2007, 2007Conference paper (Refereed)
  • 233. Clarkson, James
    et al.
    Probst, Fey
    Niranjan, Niri
    Meuli, Claudia
    Vogt, Paul
    Lidman, Disa
    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.
    Andersson, Lena
    Our experience using the vertical rectus abdominis muscle flap for reconstruction in 12 patients with dehiscence of a median sternotomy wound and mediastinitis2003In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 37, no 5, p. 266-271Article in journal (Refereed)
    Abstract [en]

    The vertical rectus abdominis (VRAM) flap has been used for reconstruction of sternal defects, particularly in the interior third, since it was first described 20 years ago. We describe 12 patients with mediastinitis or chronic sternal osteomyelitis after sternotomy treated between 1994 and 1997, nine performed at the Royal Hospitals Trust, London. Sternal osteomyelitis and mediastinitis after median sternotomy is an uncommon (0.4%-8.4%) but often fatal condition. Vascularised pedicles are the treatment of choice, and VRAM flaps were used in all cases. We report good long-term outcome with a follow up of 2-5 years, and no long-term morbidity relating to the VRAM reconstruction. We had only one partial failure of a flap. The operations were largely done in hospitals away from the plastic surgical unit in extremely sick patients, which illustrates the importance of multidisciplinary management to reduce hospital stay, mortality, and morbidity. We argue that early involvement of plastic surgical specialists in the treatment of sternal dehiscence is essential to ensure a successful outcome.

  • 234.
    Clinchy, Birgitta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery.
    Fransson, Annelie
    Druvefors, Pelle
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Hellsten, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery.
    Håkansson, Annika
    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.
    Gustafsson, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Håkansson, Leif
    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.
    Preoperative interleukin-6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma2007In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 109, no 9, p. 1742-1749Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. Colorectal cancer is one of the most common forms of cancer in the Western world. Staging based on histopathology is currently the most accurate predictor of outcome after surgery. Colorectal cancer is curable if treated at an early stage (stage I-III). However, for tumors in stages II and III there is a great need for tests giving more accurate prognostic information defining the patient population in need of closer follow-up and/or adjuvant therapy. Furthermore, tests that provide prognostic information preoperatively could provide a guide both for preoperative oncologic treatment and the surgical procedure. METHODS. Peripheral blood mononuclear cells (PBMCs) were isolated preoperatively, within a week before primary surgery, from 39 patients undergoing surgery for colorectal cancer. The PBMCs were cultured in vitro for 24 hours in the presence of autologous serum and lipopolysaccharide (LPS). Interleukin-6 (IL-6) production was measured with enzyme-linked immunosorbent assay (ELISA). Staging based on histopathology was performed in all patients. Patients were followed for at least 54 months. RESULTS. A production of >5000 pg/mL of IL-6 identified colorectal cancer patients with a poor prognosis. Eight out of 13 patients with >5000 pg/mL IL-6 died from cancer within the follow-up period, whereas no cancer-related deaths were recorded among 21 patients with 5000 pg/mL IL-6 or less. A multivariate Cox regression analysis, stratified for T- and N-stage, identified IL-6 production as an independent prognostic factor. CONCLUSIONS. IL-6 production in vitro by PBMC can predict survival after radical surgery for colorectal cancer. © 2007 American Cancer Society.

  • 235. Clinchy, Birgitta
    et al.
    Gunnerås, Marie
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Håkansson, Annika
    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.
    Håkansson, Leif
    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.
    Production of IL-1Ra by human mononuclear blood cells in vitro: Influence of serum factors2006In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 34, no 5-6, p. 320-330Article in journal (Refereed)
    Abstract [en]

    In vitro cell culture models that measure cytokine production can be of great value when analyzing regulatory mechanisms underlying various pathological conditions. However, testing the function of peripheral blood cells has to take into consideration that serum factors are likely to be of importance in maintaining their function. Interleukin-1 receptor antagonist (IL-1Ra) is a cytokine of key importance in immune regulation and is believed to be involved in numerous pathological processes, such as autoimmunity and cancer. We investigated the influence of normal, human serum on spontaneous production of IL-1Ra by human peripheral blood mononuclear cells (PBMC) in vitro. IL-1Ra production in vitro spanned over a wide range of concentrations, which could be attributed to a combined effect of both cellular parameters and properties of the serum used. The production of IL-1Ra in vitro could be correlated to the level of immobilized IgG, especially IgG1 and IgG3, which is adsorbed from the serum and bound to the tissue culture wells during culture. However, the amount of serum IgG adsorbed to the tissue culture wells could not necessarily be predicted based on the serum concentration of IgG. © 2006 Elsevier Ltd. All rights reserved.

  • 236.
    Clinchy, Birgitta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Youssefi, Reza
    Håkansson, Leif
    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.
    Differences in adsorption of serum proteins and production of IL-1ra by human monocytes incubated in different tissue culture microtiter plates2003In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 282, no 1-2, p. 53-61Article in journal (Refereed)
    Abstract [en]

    In vitro cell culture models can be of great value in order to further analyze the regulatory mechanisms underlying the inappropriate function of the immune system in diseases such as autoimmunity and cancer. Cell culture conditions have to be well controlled in a way that they mirror the in vivo situation. The objective of this study was to compare tissue culture microtiter plates from different manufacturers with respect to their ability to support monokine production by human monocytes cultured in human serum. Tissue culture ware, made of polystyrene, undergoes treatment by the manufacturers to make the surface more suitable for culture of adherent cell populations. It is possible that quality differences in this treatment can lead to variations in protein binding properties and thereby influence the adherence and functional properties of monocytes. We measured spontaneous interleukin-1 receptor antagonist (IL-1ra) production by peripheral blood monocytes, cultured in human serum, in five different microtiter plates made for adherent cell culture. Culture in plates from two of the five manufacturers resulted in significantly lower amounts of secreted IL-1ra. IL-1ra release by human monocytes can be induced by adherent IgG cross-linking membrane receptors for the Fc part of IgG (Fc?R). We found that reduced IL-1ra production coincided with a reduced capacity for binding of serum IgG in one case. Furthermore, this brand of microtiter plate also displayed the lowest level of adsorption of human albumin. We conclude that the protein adsorption properties of the plastic tissue culture ware have to be taken into consideration when assessing monokine production by human monocytes in vitro.

  • 237.
    Coble, Britt-Inger
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Nordahl-Åkesson, E
    Vinnerberg, Å
    Kihlström, Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Urine-based testing for Chlamydia trachomatis using polymerase chain reaction, leucocyte esterase and urethral and cervical smears2006In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 66, no 4, p. 269-278Article in journal (Refereed)
    Abstract [en]

    The performance of Roche polymerase chain reaction (PCR) Amplicor to detect Chlamydia trachomatis in first-voided urine specimens from 422 males and 456 females attending two clinics for sexually transmitted infections was evaluated in comparison with cultures of urethral and cervical specimens. At the same time, the ability of leucocyte esterase (LE) in first-voided urine and the presence of leucocytes in urethral and cervical smears to identify C. trachomatis -infected individuals based on PCR and culture was determined. The prevalence of C. trachomatis infection was 10.9 % in men and 7.7 % in women. Sensitivity, specificity, positive predictive value and negative predictive value of Amplicor was 93.5 %, 99.7 %, 97.7 % and 99.2 % in males and 91.4 %, 99.5 %, 94.1 % and 99.3 % in females. All Chlamydia-infected men were identified by means of a combination of urethritis (≥4 leucocytes in the urethral smear) and/or a positive LE test in urine, although the specificity was only 42.2 %. In women, the combination of urethritis and/or cervicitis and/or a positive LE test identified 85.7 % of Chlamydia-infected patients with a specificity of 38.2 %. It is concluded that a combination of urethral and/or cervical smears and LE testing of urine can be used as a screening test to select patients, especially males, for specific C. trachomatis testing.

  • 238.
    Colnerud Nilsson, Emma
    Linköping University, Department of Biomedicine and Surgery.
     Salivary cortisol and post traumatic stress symptoms  : -a ten year follow-up of Swedish UN soldiers after a 6 months mission in Bosnia2009Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This is to my knowledge the first time a ten-year follow-up study of salivary cortisol concentrations measured by immunoassays in relation to posttraumatic symptoms according to the Impact of Event Scale (IES) is made. The study was performed on 78 Swedish UN soldiers after a 6-months mission in the former republic of Yugoslavia. Follow-up investigations were performed six months, twelve months and ten years after their return to Sweden. Morning and evening salivary cortisol concentrations were determined by radioimmunoassay (RIA) and enzyme-linked immunoassay (EIA) and subjective posttraumatic avoidance and intrusion symptoms were measured with the IES (see Appendix I).

     

    This study concerns the methodological description of the EIA for determination of salivary cortisol and the comparison of the results from all three follow-up investigations. Post-traumatic stress symptoms according to IES (intrusion subscale and total score) increased significantly over ten years of time. There was an significant interrelationship between the change in both morning and evening salivary cortisol concentrations, measured with immunoassays, and changes in self-rated posttraumatic intrusive symptoms, according to IES, during ten years follow-up, after a six months mission in Bosnia in the way that salivary cortisol concentrations showed a tendency to decrease over ten years of time in subjects with a higher IES score. The rise in morning salivary cortisol, from awakening until 30 minutes later, was significantly correlated with the ratings of posttraumatic stress symptoms according to the IES ten years after the mission.   

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  • 239. Corman, ML
    et al.
    Gravié, J-F
    Hager, T
    Loudon, MA
    Mascagni, D
    Nyström, Per-Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Seow-Choen, F
    Abcarian, H
    Marcello, P
    Weiss, E
    Longo, A
    Stapled haemorrhoidopexy: a consensus position paper by an international working party - indications, contra-indications and technique2003In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 5, p. 304-310Article in journal (Refereed)
  • 240. Costa, M
    et al.
    Glise, H
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    The enteric nervous system in health and disease. Workshop.2000In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 47Article in journal (Other (popular science, discussion, etc.))
  • 241. Craig, AD
    et al.
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Is there a specific lamina I spinothalamocortical pathway for pain and temperature sensations in primates?2002In: Journal of Pain, ISSN 1526-5900, E-ISSN 1528-8447, Vol. 3, no 2Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 242. Craig, AD
    et al.
    Zhang, ET
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    A distinct thermoreceptive subregion of lamina I in nucleus caudalis of the owl monkey.1999In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 404, p. 221-234Article in journal (Refereed)
  • 243. Craig, AD
    et al.
    Zhang, ET
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Association of spinothalamic lamina I neurons and their ascending axons with calbindin-immunoreactivity in monkey and human2002In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 97, no 1-2, p. 105-115Article in journal (Refereed)
    Abstract [en]

    The calbindin-immunoreactivity of spinothalamic (STT) lamina I neurons and their ascending axons was examined in two experiments. In the first experiment, lamina I STT neurons in macaque monkeys were double-labeled for calbindin and for retrogradely transported WGA*HRP following large (n=2) or small (n=1) injections that included the posterior thalamus. Most, but not all (78%) of the contralateral retrogradely labeled lamina I STT cells were positive for calbindin. Calbindin-immunoreactivity was not selectively associated with any particular anatomical type of lamina I STT cell, 82% of the fusiform cells, 78% of the pyramidal cells and 67% of the multipolar cells were double-labeled. In the second experiment, oblique transverse sections from upper cervical spinal segments of three macaque monkeys, one squirrel monkey and five humans were stained for calbindin-immunoreactivity. In each case, a distinct bundle of fibers was densely stained in the middle of the lateral funiculus. This matches the location of anterogradely labeled ascending lamina I axons observed in prior work in cats and monkeys, and it matches the location of the classically described 'lateral spinothalamic tract' in humans. This bundle had variable shape across cases, an observation that might have clinical significance. These findings support the view that lamina I STT neurons are involved in spinal cordotomies that reduce pain, temperature and itch sensations. ⌐ 2002 International Association for the study of Pain. Published by Elsevier Science B.V. All rights reserved.

  • 244.
    Dabrosin, Charlotta
    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.
    Increase of free insulin-like growth factor-1 in normal human breast in vivo late in the menstrual cycle2003In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 80, no 2, p. 193-198Article in journal (Refereed)
    Abstract [en]

    Prolonged exposure to endogenous and exogenous sex steroids increases the risk of breast cancer but the mechanisms are poorly understood. Increased levels of circulating insulin-like growth factor-1 (IGF-1) and low levels of IGF binding protein are associated with increased risk of breast cancer suggesting that IGF-1 has to be in its free form to be biologically active. Little is known about sex steroid regulation of IGF-1 locally in the breast. In this study microdialysis was used to determine the local levels of free IGF-1 in normal human breast tissue in healthy female volunteers during the menstrual cycle. The results showed that the extracellular levels of free IGF-1 locally in the breast were doubled in the luteal phase, when estradiol and progesterone levels were elevated, compared with the follicular phase. In plasma, free IGF-1 levels also exhibited a cyclic variation but to a less extent. The increased local levels of the tree form of IGF-1 may promote proliferation in the breast epithelium. This could be important in sex steroid dependent breast cancer development.

  • 245.
    Dabrosin, Charlotta
    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.
    Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle2005In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 187, no 1, p. 103-108Article in journal (Refereed)
    Abstract [en]

    Estrogen exposure is a major risk factor for breast cancer. Tissue estrogen originates from the ovaries but a significant portion is also produced by enzyme activity locally in the breast itself. How these enzymes are regulated is not fully understood. The extracellular space, where the metabolic exchange and cell interactions take place, reflects the environment that surrounds the epithelium but there has been no previous study of hormone concentrations in this compartment. In the present study microdialysis was used to measure extracellular estrogen concentrations in breast tissue and abdominal subcutaneous fat in 12 healthy women in vivo. It was found that women with high plasma progesterone levels had significant increased levels of estradiol in breast tissue compared with fat tissue (breast tissue 168 ± 6 pM, subcutaneous fat, 154 ± 5 pM, P<0.05), whereas women with low plasma progesterone exhibited no difference. Moreover, there was a significant correlation between local breast tissue estradiol and plasma progesterone levels (r=0.709, P<0.01). There was no difference in estrone sulphate in breast and fat tissue regardless of progesterone levels. Estrone was not detectable. The results in this study suggest that progesterone may be one regulator in the local conversion of estrogen precursors into potent estradiol in normal breast tissue. © 2005 Society for Endocrinology.

  • 246.
    Dabrosin, Charlotta
    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.
    Microdialysis - an in vivo technique for studies of growth factors in breast cancer.2005Article in journal (Refereed)
    Abstract [en]

    Changes in the microenvironment are important in the development of cancer and further tumor growth. Although landmark discoveries have been made regarding genetic alterations in cancer at a cellular level very little is known about protein regulation in the extracellular space. In the microenvironment many growth factors are activated at a post-translational level by interactions of different cell types such as epithelial cells, fibroblasts, adipose cells, and immune cells. The extracellular space is the bioactive site for the majority of growth factors and increased knowledge of protein activation in this compartment is of utmost importance for our comprehension of tumor biology. Microdialysis is a minimally invasive technique, which enables sampling of molecules in the extracellular space. It is applicable in human cancer as well as in experimental tumors. This review describes microdialysis, its application and the up to date literature of microdialysis for detection of growth factors in cancer with special emphasis on breast cancer.

  • 247.
    Dabrosin, Charlotta
    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.
    Positive correlation between estradiol and vascular endothelial growth factor but not fibroblast growth factor-2 in normal human breast tissue in vivo2005In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 11, no 22, p. 8036-8041Article in journal (Refereed)
    Abstract [en]

    Purpose: Angiogenesis is crucial in tumor development and progression. Ovarian hormones regulate angiogenesis in the reproductive tract but very little is known about its regulation in the normal breast. Sex steroids play an important role in breast cancer development by poorly understood mechanisms. Vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) are potent stimulators of angiogenesis. Both VEGF and FGF-2 function in autocrine/ paracrine pathways and there is a major contribution of bioactive proteins by a posttranslational activation of sequestered molecules in the extracellular space. A direct measurement of these molecules in the extracellular compartment is, therefore, needed. Experimental Design: In this study, microdialysis was used to measure extracellular VEGF and FGF-2 in normal human breast tissue in situ in 11 premenopausal and 5 postmenopausal women. Results: Significantly higher level of VEGF in breast tissue of premenopausal women was found. Plasma as well as local estradiol and breast tissue VEGF exhibited significant correlations, whereas progesterone had no correlation with breast VEGF. FGF-2 did not correlate with either estradiol or progesterone. Conclusion: The result suggests that estradiol is a more potent regulator of free VEGF levels than progesterone in the normal breast. The control of free FGF-2 seems to be independent of sex steroids in the breast. Estrogen induction of free extracellular VEGF may be one mechanism involved in sex steroid - dependent breast carcinogenesis. © 2005 American Association for Cancer Research.

  • 248.
    Dabrosin, Charlotta
    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.
    Sex steroid regulation of angiogenesis in breast tissue2005In: Angiogenesis, ISSN 0969-6970, E-ISSN 1573-7209, Vol. 8, no 2, p. 127-136Article in journal (Refereed)
    Abstract [en]

    Angiogenesis is essential for normal function in the female reproductive tract and a prerequisite for growth and metastasis of solid tumors. Several factors, both inducers and inhibitors, play essential roles in the regulation of the angiogenic process. Exposure to sex steroids increases the risk of breast cancer but the mechanisms are poorly understood and the importance of angiogenesis in breast carcinogenesis is undefined. In the female reproductive tract ovarian hormones tightly regulate angiogenesis. The breast is also a target organ for sex steroids but very little is known about sex steroid effects on angiogenesis in normal breast tissue and breast cancer. In this review several regulators of angiogenesis, and their relation to sex steroids, in breast tissue are discussed. Increased knowledge in this area is of utmost importance for future therapeutic treatment options and for breast cancer prevention. © Springer 2005.

  • 249.
    Dabrosin, Charlotta
    et al.
    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.
    Johansson, Ann-Charlotte
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology.
    Öllinger, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Decreased secretion of Cathepsin D in breast cancer in vivo by tamoxifen: Mediated by the mannose-6-phosphate/IGF-II receptor?2004In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 85, no 3, p. 229-238Article in journal (Refereed)
    Abstract [en]

    The lysosomal protease Catliepsin D (Cath D) is associated with increased invasiveness and metastasis in breast cancer. Both estrogen and tamoxifen have been reported to increase Cath D, which seems to contradict the efficacy of tamoxifen as an adjuvant for estrogen dependent breast cancer. Cath D is bioactive in the extracellular space but very little is known about hormonal regulation of secreted Cath D in vivo. In this study we used microdialysis to sample the extracellular fluid in estrogen receptor positive MCF-7 tumors in nude mice. We show that tamoxifen in combination with estradiol decreased secreted Cath D compared with estradiol treatment only in solid tumors in situ. Cell culture of MCF-7 cells revealed that estradiol and tamoxifen increased intracellular proteolytic activity of Cath D in a similar fashion whereas secretion of Cath D was increased by estradiol and inhibited by tamoxifen. Immunofluorescence showed that estradiol located Cath D to the cell surface, while tamoxifen accumulated Cath D to dense lysosomes in perinuclear regions. Moreover, tamoxifen increased the intracellular transporter of Cath D, the mannose 6-phosphate/IGF-II receptor (M6P/IGF2R). In contrast, estradiol decreased the levels of this receptor. Thus, secretion of Cath D is hormone dependent and may be mediated by altered expression of the M6P/IGF2R. Our results highlight the importance of measurements of proteins in all compartments where they are biological active and show that microdialysis is a viable technique for sampling of Cath D in vivo.

  • 250.
    Dabrosin, Charlotta
    et al.
    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.
    Margetts, Peter J
    Gauldie, Jack
    Estradiol increases extracellular levels of vascular endothelial growth factor in vivo in murine mammary cancer2003In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 107, no 4, p. 535-540Article in journal (Refereed)
    Abstract [en]

    Angiogenesis is essential for tumor growth and metastasis and an important prognostic factor in breast cancer. VEGF, a key factor for angiogenesis, has been correlated with tumor vessel density in breast cancer. Estrogen, another crucial factor in breast cancer, stimulates VEGF, and an ERE in the VEGF gene has been defined. VEGF is bioactive in the extracellular fluid, where it becomes available to endothelial cells. Whether E2 affects VEGF levels in the extracellular fluid is not known. We show, using intratumoral microdialysis in vivo, that E2 treatment increased tumor extracellular levels of VEGF in an estrogen-dependent breast cancer model. Moreover, extracellular levels of VEGF in the tumor showed a strong correlation with total tumor VEGF, contrary to plasma levels of VEGF. Ninety-three percent of measured VEGF in the extracellular fluid in the tumor was tumor-derived, while only 45% of VEGF in circularing plasma originated from the tumor. We conclude that E2 increases extracellular VEGF and that microdialysis is a sensitive method for measurement of local VEGF production in vivo. Our results have potential application to the assessment of tumor characteristics in vivo in human tumors for individualized cancer therapy.

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