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  • 51. Kostova, Nora
    et al.
    Srebreva, Ljuba N
    Milev, Angel D
    Bogdanova, Olga G
    Rundquist, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Lindner, Herbert H
    Markov, Dimiter V
    Immunohistochemical demonstration of histone H10 in human breast carcinoma2005In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 124, no 5, p. 435-443Article in journal (Refereed)
    Abstract [en]

    Histone H10 is a linker histone subvariant present in tissues of low proliferation rate. It is supposed to participate in the expression and maintenance of the terminal differentiation phenotype. The aim of this work was to study histone H10 distribution in human breast carcinoma and its relationship with the processes of proliferation and differentiation. Most of the cells in carcinomas of moderate and high level of differentiation expressed histone H10 including cells invading connective and adipose tissues. In low differentiated tumours, the number of H10 expressing cells was considerably lower. Staining of myoepithelial cells, when seen, and of stromal fibroblasts was variable. The metastatic malignant cells in the lymph nodes also accumulated H10 but lymphocytes were always negative. All immunopositive malignant cells exhibited signs of polymorphism. Double H1 0/Ki-67 staining showed that the growth fraction in more differentiated tumours belonged to the H10-positive cells, while in poorly differentiated carcinomas it also included a cell subpopulation not expressing H10. If expressed, p27Kip1 was always found in H10-positive cells. These findings are inconsistent with the widespread view that histone H10 is expressed only in terminally differentiated cells. Rather, they suggest that the protein is expressed in cells in a prolonged intermitotic period irrespective of their level of differentiation. Double H10/Ki-67 immunostaining could be a useful tool in studying the growth fraction in tumours. © Springer-Verlag 2005.

  • 52.
    Lagergren, Anna
    et al.
    Department for Hematopoetic Stem Cell Biology, Lund Stemcell Center, Lund University, Lund, Sweden.
    Månsson, Robert
    Department for Hematopoetic Stem Cell Biology, Lund Stemcell Center, Lund University, Lund, Sweden.
    Zetterblad, Jenny
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Smith, Emma
    Department for Hematopoetic Stem Cell Biology, Lund Stemcell Center, Lund University, Lund, Sweden.
    Basta, Barbro
    Department of Molecular Pharmacology, AstraZeneca R&D Mölndal, Sweden.
    Bryder, David
    Department for Hematopoetic Stem Cell Biology, Lund Stemcell Center, Lund University, Lund, Sweden.
    Åkerblad, Peter
    Department of Molecular Pharmacology, AstraZeneca R&D Mölndal, Sweden.
    Sigvardsson, Mikael
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    The Cxcl12, Periostin, and Ccl9 genes are direct targets for early B-cell factor in OP-9 stroma cells2007In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 282, no 19, p. 14454-14462Article in journal (Refereed)
    Abstract [en]

    The development of blood cells from hematopoietic stem cells in the bone marrow is dependent on communication with bone marrow stroma cells, making these cells central for the appropriate regulation of hematopoiesis. To identify transcription factors that may play a role in gene regulation in stroma cells, we performed comparative gene expression analysis of fibroblastic NIH3T3 cells, unable to support hematopoiesis in vitro, and OP-9 stroma cells, highly efficient in this regard. These experiments revealed that transcription factors of the early B cell factor (EBF) family were highly expressed in OP-9 cells as compared with the NIH3T3 cells. To identify potential targets genes for EBF proteins in stroma cells, we overexpressed EBF in fibroblasts and analyzed the pattern of induced genes by microarray analysis. This revealed that EBF was able to up-regulate expression of among others the Cxcl12, Ccl9, and Periostin genes. The identification of relevant promoters revealed that they all contained functional EBF binding sites able to interact with EBF in OP-9 cells. Furthermore, ectopic expression of a dominant negative EBF protein or antisense EBF-1 RNA in OP-9 stroma cells resulted in reduced expression of these target genes. These data suggest that EBF proteins might have dual roles in hematopoiesis acting both as intrinsic regulators of B-lymphopoiesis and as regulators of genes in bone marrow stroma cells. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

  • 53. Larsson, Annika
    et al.
    Söderberg, Linda
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Sletten, Knut
    Engström, Ulla
    Tjernberg, Lars O
    Näslund, Jan
    Westermark, Per
    Unwinding fibril formation of medin, the peptide of the most common form of human amyloid2007In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 361, no 4, p. 822-828Article in journal (Refereed)
    Abstract [en]

    Medin amyloid affects the medial layer of the thoracic aorta of most people above 50 years of age. The consequences of this amyloid are not completely known but the deposits may contribute to diseases such as thoracic aortic aneurysm and dissection or to the general diminished elasticity of blood vessels seen in elderly people. We show that the 50-amino acid residue peptide medin forms amyloid-like fibrils in vitro. With the use of Congo red staining, Thioflavin T fluorescence, electron microscopy, and a solid-phase binding assay on different synthetic peptides, we identified the last 18-19 amino acid residues to constitute the amyloid-promoting region of medin. We also demonstrate that the two C-terminal phenylalanines, previously suggested to be of importance for amyloid formation, are not required for medin amyloid formation.

  • 54.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Haglund, Sofie
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Taipalensuu, Jan
    Division of Research and Development in Laboratory Medicine, Ryhov County Hospital, Jönköping.
    Hertervig, Erik
    dDepartment of Medicine, Lund University Hospital, Lund.
    Lyrenäs, Ebbe
    Department of Medicine, Blekinge County Hospital, Karlskrona.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Identification of two novel sequence variants affecting thiopurine methyltransferase enzyme activity2004In: Pharmacogenetics, ISSN 0960-314X, E-ISSN 1473-561X, Vol. 14, no 4, p. 261-265Article in journal (Refereed)
    Abstract [en]

    The polymorphic enzyme thiopurine methyltransferase (TPMT) is involved in the methylation of thiopurines. On comparing the phenotype with the genotype in Swedish patients with inflammatory bowel disease and healthy individuals, we found two discordant cases with low TPMT enzyme activity (0.3 and 0.4 U/ml packed red blood cells (pRBC). Genotyping by pyrosequencing revealed that they carried the nucleotide substitutions 460G>A and 719A>G, giving two possible genotypes (TPMT*1/*3A or TPMT*3B/ *3C). DNA sequencing of exon III to X was performed in the patients and their parents. We identified an A>G transition in the start codon (exon III, 1A>G, Met>Val, TPMT*14) in one of the patients and her father (6.3 U/ml pRBC). The mother in this family carried the 460G>A and 719A>G nucleotide substitutions (TPMT*3A, 5.0 U/ml pRBC). In the second family, sequencing revealed a G>A transition in the acceptor splice site in intron VII/exon VIII (IVS7 - 1G>A, TPMT*15) in the patient and his mother (6.9 U/ml pRBC). His father was genotyped as TPMT*1/*3A (6.0 U/ml pRBC). Hence, we report the identification of two novel sequence variants, present in highly conserved nucleotide positions of the human TPMT gene, resulting in a loss of enzyme activity.

  • 55.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hindorf, U
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    No induction of thiopurine methyltransferase during thiopurine treatment in inflammatory bowel disease2006In: Nucleosides, Nucleotides & Nucleic Acids, ISSN 1525-7770, E-ISSN 1532-2335, Vol. 25, no 9-11, p. 1033-1037Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to follow, during standardized initiation of thiopurine treatment, thiopurine methyltransferase (TPMT) gene expression and enzyme activity and thiopurine metabolite concentrations, and to study the role of TPMT and ITPA 94C > A polymorphisms for the development of adverse drug reactions. Sixty patients with ulcerative colitis or Crohn's disease were included in this open and prospective multi-center study. Thiopurine naïve patients were prescribed azathioprine (AZA), patients previously intolerant to AZA received 6-mercaptopurine (6-MP). The patients followed a predetermined dose escalation schedule, reaching target dose at Week 3, 2.5 and 1.25 mg/kg body weight for AZA and 6-MP, respectively. The patients were followed every week during Weeks 1-8 from baseline and then every 4 weeks until 20 weeks. TPMT activity and thiopurine metabolites were determined in erythrocytes, TPMT and ITPA genotypes, and TPMT gene expression were determined in whole blood. One homozygous TPMT-deficient patient was excluded. Five non compliant patients were withdrawn during the first weeks. Twenty-seven patients completed the study per protocol, 27 patients were withdrawn because of adverse events. Sixty-seven percent of the withdrawn patients tolerated thiopurines at a lower dose at Week 20. There was no difference in baseline TPMT enzyme activity between individuals completing the study and those withdrawn for adverse events (p = 0.45). A significant decrease in TPMT gene expression (TPMT/huCYC ratio, p = 0.02) was found, however TPMT enzyme activity did not change. TPMT heterozygous individuals had a lower probability of remaining in the study on the predetermined dose (p = 0.039). The ITPA 94C > A polymorphism was not predictive of adverse events (p = 0.35). Copyright © Taylor & Francis Group, LLC.

  • 56.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hindorf, Ulf
    Lund.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Molecular and Clinical Medicine.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    No induction of thiopurine methyltransferase (TPMT) during thiopurine treatment in IBD2005In: 10th Symposium European Society for the Study of Purine and Pyrimidine Metabolism in Man,2005, 2005Conference paper (Refereed)
  • 57.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hindorf, Ulf
    Lund.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Molecular and Clinical Medicine.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    No induction of thiopurine methyltransferase (TPMT) during thiopurine treatment in IBD2005In: 13th United European Gastroenterology week,2005, Stuttgart: Georg Thieme Verlag KG , 2005, p. A173-Conference paper (Refereed)
  • 58.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Skoglund, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Karlgren, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Kidhall, Irene
    Danderyds sjukhus.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Explaining TPMT genotype/phenotype discrepancy by haplotyping of TPMT*3A and identification of a novel sequence variant, TPMT*232007In: Pharmacogenetics and Genomics, ISSN 1744-6872, Vol. 17, no 10, p. 891-895Article in journal (Refereed)
    Abstract [en]

    Thiopurine methyltransferase (TPMT) is a polymorphic enzyme involved in the metabolism of thiopurine drugs. Owing to polymorphisms in the TPMT gene (TPMT*2-*22), the enzyme activity varies interindividually. Patients with reduced TPMT activity may develop adverse reactions when treated with standard doses of thiopurines. This work focuses on a TPMT genotype/phenotype discrepancy found in a patient during routine testing. The patient displayed very low TPMT enzyme activity and she was genotyped by pyrosequencing as being heterozygous for the 460G>A and 719A>G polymorphisms (TPMT*3A). Complete sequencing in combination with haplotyping of the TPMT gene revealed a novel sequence variant, 500C>G, on one allele and TPMT*3A on the other allele, giving rise to the novel genotype TPMT*3A/*23. When investigating the patient's relatives, they too had the TPMT*3A/*23 genotype in combination with low enzyme activity. We conclude that this novel variant allele affects enzyme activity, as the individuals carrying it had almost undetectable TPMT activity. © 2007 Lippincott Williams & Wilkins, Inc.

  • 59.
    Lindström, Sivert
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Mazières, Leonor
    Jiang, Chonghe
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Inhibition of the bladder cooling reflex in the awake state: An experimental study in the cat2004In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 172, no 5 I, p. 2051-2053Article in journal (Refereed)
    Abstract [en]

    Purpose: We assessed the bladder cooling reflex in the awake cat. The bladder cooling reflex is consistently observed in anesthetized adult cats but not in awake, neurologically normal humans. This discrepancy could indicate a state dependant control of the reflex or a species difference. This study was designed to differentiate between these alternatives. Materials and Methods: Under ketamine-xylazine 5 animals had an indwelling catheter inserted into the bladder. The cooling reflex was tested by injections of cold saline into the bladder (4C to 8C), lowering its wall temperature to about 30C to 32C. The volume used (5 ml) was subthreshold for the Aδ micturition reflex, as confirmed by control injections of body warm saline. The procedure was repeated with the animals fully awake and it was well tolerated by all of them. Reflex responses were assessed by induced bladder pressures. Results: Typical bladder cooling reflexes with peak pressures greater than 3 kPa were evoked in all cats when in narcotic sleep (group mean ± CI 7.4 ± 3.1 kPa). No such reflexes were elicited when the animals were awake (2.0 ± 1.0 kPa). The difference was significant at the level of individual animals. Conclusions: The bladder cooling reflex is suppressed in adult cats during wakefulness, as in humans. This state dependent control of the bladder cooling reflex adds to its resemblance to the extensor plantar response (Babinski's sign).

  • 60. Littorin, B
    et al.
    Blom, P
    Schölin, A
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Blohmé, G
    Bolinder, J
    Ekbom-Schnell, A
    Eriksson, JW
    Gudbjörnsdottir, S
    Nyström, L
    Östman, J
    Sundkvist, G
    Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: Results from the nationwide Diabetes Incidence Study in Sweden (DISS)2006In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, no 12, p. 2847-2852Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Low plasma vitamin D concentrations may promote the development of type 1 diabetes. To test this hypothesis, we measured plasma 25-hydroxyvitamin D (25OHD) in young adults with type 1 diabetes. Methods: The nationwide Diabetes Incidence Study in Sweden (DISS) covers 15- to 34-year-old people with newly diagnosed diabetes. Blood samples at diagnosis were collected during the 2-year period 1987/1988. Patients with islet antibodies (islet cell antibodies, GAD antibodies or tyrosine phosphatase-like protein antibodies) were defined as having autoimmune type 1 diabetes. Plasma 25OHD was measured in samples taken from 459 patients at the time of diagnosis, and in 138 of these subjects 8 years later. The results were compared with age- and sex-matched control subjects (n=208). Results: At diagnosis, plasma 25OHD levels were significantly lower in patients with type 1 diabetes than in control subjects (82.5±1.3 vs 96.7±2.0 nmol/l, p<0.0001). Eight years later, plasma 25OHD had decreased in patients (81.5±2.6 nmol/l, p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9±1.4 vs 90.1±2.4 nmol/l, p<0.0001) and at follow-up (77.1±2.8 nmol/l vs 87.2±4.5 nmol/l, p=0.048). Conclusions/interpretation: The plasma 25OHD level was lower at diagnosis of autoimmune type 1 diabetes than in control subjects, and may have a role in the development of type 1 diabetes. Plasma 25OHD levels were lower in men than in women with type 1 diabetes. This difference may be relevant to the high incidence of type 1 diabetes among young adult men. © 2006 Springer-Verlag.

  • 61. Lund, Lars H
    et al.
    Andersson, Karolina
    Zuber, Bartek
    Karlsson, Anneli
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Engström, Gunnel
    Hinkula, Jorma
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology.
    Wahren, Britta
    Winberg, Gösta
    Signal sequence deletion and fusion to tetanus toxoid epitope augment antitumor immune responses to a human carcinoembryonic antigen (CEA) plasmid DNA vaccine in a murine test system2003In: Cancer Gene Therapy, ISSN 0929-1903, E-ISSN 1476-5500, Vol. 10, p. 365-376Article in journal (Refereed)
  • 62.
    Lystedt, Erika
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care.
    Westergren, Hanna
    Brynhildsen, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Lindh-Åstrand, Lotta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Gustavsson, Johanna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hammar, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Strålfors, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Subcutaneous adipocytes from obese hyperinsulinemic women with polycystic ovary syndrome exhibit normal insulin sensitivity but reduced maximal insulin responsiveness2005In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 153, no 6, p. 831-835Article in journal (Refereed)
    Abstract [en]

    Background: Polycystic ovary syndrome (PCOS) has a high prevalence in women and is often associated with insulin resistance and hence with aspects of the so-called metabolic syndrome. Methods: Ten women diagnosed with PCOS were consecutively included (aged 21-39 years, average 30.2±1.9 years, body mass index 28.4-42.5 kg/m2, average 37.5±1.7 kg/m2 (mean±S.E.)). Adipocytes were isolated from the subcutaneous fat and, after overnight incubation to recover from insulin resistance due to the surgical cell isolation procedures, they were analyzed for insulin sensitivity. Results: The patients with PCOS exhibited marked clinical hyperinsulinemia with 3.6-fold higher blood levels of C-peptide than a healthy lean control group (1.7±0.2 and 0.5±0.02 nmol/l respectively, P < 0.0001). The patients with PCOS also exhibited 2.4-fold higher concentrations of serum triacylglycerol (2.1±0.3 and 0.9±0.06 mmol/l respectively, P < 0.0001), but only slightly elevated blood pressure (118±12/76±6 and 113±7/72±6 mmHg respectively, P = 0.055/0.046). However, insulin sensitivity for stimulation of glucose transport in the isolated adipocytes was indistinguishable from a non-PCOS, non-diabetic control group, while the maximal insulin effect on glucose uptake was significantly lower (2.2±0.2- and 3.8±0.8-fold respectively, P = 0.02). Conclusions: Subcutaneous adipocytes from patients with PCOS do not display reduced insulin sensitivity. The findings show that the insulin resistance of PCOS is qualitatively different from that of type 2 diabetes. © 2005 Society of the European Journal of Endocrinology.

  • 63. Mazières, L
    et al.
    Jiang, Chonghe
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Lindström, Sivert
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Recurrent inhibition of the bladder C fibre reflex in the cat and its response to naloxone2006In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 575, no 2, p. 603-615Article in journal (Refereed)
    Abstract [en]

    Recurrent inhibition of the bladder C fibre reflex was studied in adult female cats anaesthetized with α-chloralose. Test reflexes were evoked by electrical stimulation of bladder Aδ and C afferents in the right pelvic nerve and were recorded from the proximal end of a small ipsilateral pelvic nerve branch, transected close to the bladder. Such test reflexes were consistently depressed by repetitive electrical stimulation of the contralateral bladder pelvic nerve (20 Hz, 20 s) at intensities sufficient to recruit axons of bladder preganglionic neurones. The inhibition could be evoked after transection of the left dorsal roots S1-S4 and the sympathetic supply to the bladder but was abolished by transection of the pelvic nerve central to the site of stimulation. Hence, it most likely involved central recurrent collaterals of antidromically activated bladder preganglionic neurones. The reflex suppression was quite considerable -maximal C fibre reflexes were reduced to a group mean of 25% (± 9% confidence interval) of their control size. The effect had a slow onset, requiring a few seconds of conditioning stimulation to be revealed, and was very long lasting (minutes). Naloxone (0.01-0.5 mg kg-1 i.v.) abolished the recurrent inhibition of both the C fibre and Aδ bladder reflexes, while inhibition from afferents in the dorsal clitoris nerve remained unchanged. It is concluded that the segmental bladder C fibre reflex and the spino-ponto-spinal Aδ micturition reflex are both targets of recurrent inhibition from bladder parasympathetic preganglionic neurones and that the effect involves an enkephalinergic mechanism. 2006 The Authors. Journal compilation © 2006 The Physiological Society.

  • 64.
    Mazières, Leonor
    et al.
    Service de Rééducation Neurologique, Hôpital de la Salpêtrière, 47-83 boulevard de lHôpital, 75651 Paris Cedex 13 France.
    Jiang, Chonghe
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Lindström, Sivert
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    The C-fibre reflex of the cat's urinary bladder1998In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 513, no 2, p. 531-541Article in journal (Refereed)
    Abstract [en]

     1. Reflexes evoked in bladder parasympathetic neurones by electrical stimulation of bladder C afferent fibres were studied in cats anaesthetized with alpha-chloralose. The responses were compared with the ordinary micturition reflex evoked by low-threshold Adelta afferents from bladder mechanoreceptors and mediated by a spino-ponto-spinal reflex pathway. 2. The bladder was catheterized for fluid instillations and pressure recordings. Efferent reflex discharges were recorded from the cut central end of a small distal bladder branch of the pelvic nerve. The remaining bladder pelvic nerve branches were stimulated electrically close to the bladder. 3. Stimulation at C afferent intensity evoked a late reflex discharge in bladder pelvic efferents in all animals. The response was centrally mediated, had a latency of 150-250 ms, and was much weaker after stimulation on the contralateral nerve. 4. The bladder C fibre reflex differed in several functional aspects from the ordinary Adelta micturition reflex. It could be evoked at a low rate of stimulation, with an empty bladder and no background activity from bladder mechanoreceptors. In this situation, the normal Adelta micturition reflex is not elicited. The C fibre reflex also survived an acute spinalization at a low thoracic level. 5. The C fibre reflex was strongly inhibited by dorsal clitoris or dorsal penis nerve stimulation, an effect that was maintained after spinalization. It was facilitated by bladder or urethra exposure to cold and menthol, stimuli that activate specific cold-sensitive receptors associated with unmyelinated C afferents. 6. It is concluded that the central pathway of the C fibre reflex is spinal and partly separate from that of the ordinary micturition reflex. These observations are in keeping with the clinical finding that a bladder cooling reflex can be elicited in patients with disturbed descending control of the bladder. 

  • 65.
    Meruvu, Sunitha
    et al.
    Avd för Cellbiologi IBK.
    Walther, Matthias
    Ivanov, Igor
    Hammarström, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Fürstenberger, Gerhard
    Krieg, Peter
    Reddanna, Pallu
    Kuhn, Hartmut
    Sequence determinants for the reaction specificity of murine (12R)-lipoxygenase: Targeted substrate modification and site-directed mutagenesis2005In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 280, no 44, p. 36633-36641Article in journal (Refereed)
    Abstract [en]

    Mammalian lipoxygenases (LOXs) are categorized with respect to their positional specificity of arachidonic acid oxygenation. Site-directed mutagenesis identified sequence determinants for the positional specificity of these enzymes, and a critical amino acid for the stereoselectivity was recently discovered. To search for sequence determinants of murine (12R)-LOX, we carried out multiple amino acid sequence alignments and found that Phe390, Gly441, Ala455, and Val631 align with previously identified positional determinants of S-LOX isoforms. Multiple site-directed mutagenesis studies on Phe390 and Ala455 did not induce specific alterations in the reaction specificity, but yielded enzyme species with reduced specific activities and stereo random product patterns. Mutation of Gly441 to Ala, which caused drastic alterations in the reaction specificity of other LOX isoforms, failed to induce major alterations in the positional specificity of mouse (12R)-LOX, but markedly modified the enantioselectivity of the enzyme. When Val631, which aligns with the positional determinant He593 of rabbit 15-LOX, was mutated to a less space-filling residue (Ala or Gly), we obtained an enzyme species with augmented catalytic activity and specifically altered reaction characteristics (major formation of chiral (11R)-hydroxyeicosatetraenoic acid methyl ester). The importance of Val631 for the stereo control of murine (12R)-LOX was confirmed with other substrates such as methyl linoleate and 20-hydroxyeicosatetraenoic acid methyl ester. These data identify Val 631 as the major sequence determinant for the specificity of murine (12R)-LOX. Furthermore, we conclude that substrate fatty acids may adopt different catalytically productive arrangements at the active site of murine (12R)-LOX and that each of these arrangements may lead to the formation of chiral oxygenation products. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

  • 66.
    Mishra, Rajesh
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Sörgjerd, Karin
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Nyström, Sofie
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Nordigården, Amanda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Chiu, Yu-Jui
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Hammarström, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Lysozyme Amyloidogenesis Is Accelerated by Specific Nicking and Fragmentation but Decelerated by Intact Protein Binding and Conversion2007In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 366, no 3, p. 1029-1044Article in journal (Refereed)
    Abstract [en]

    We have revisited the well-studied heat and acidic amyloid fibril formation pathway (pH 1.6, 65 °C) of hen egg-white lysozyme (HEWL) to map the barriers of the misfolding and amyloidogenesis pathways. A comprehensive kinetic mechanism is presented where all steps involving protein hydrolysis, fragmentation, assembly and conversion into amyloid fibrils are accounted for. Amyloid fibril formation of lysozyme has multiple kinetic barriers. First, HEWL unfolds within minutes, followed by irreversible steps of partial acid hydrolysis affording a large amount of nicked HEWL, the 49-101 amyloidogenic fragment and a variety of other species over 5-40 h. Fragmentation forming the 49-101 fragment is a requirement for efficient amyloid fibril formation, indicating that it forms the rate-determining nucleus. Nicked full-length HEWL is recruited efficiently into amyloid fibrils in the fibril growth phase or using mature fibrils as seeds, which abolished the lag phase completely. Mature amyloid fibrils of HEWL are composed mainly of nicked HEWL in the early equilibrium phase but go through a "fibril shaving" process, affording fibrils composed of the 49-101 fragment and 53-101 fragment during more extensive maturation (incubation for longer than ten days). Seeding of the amyloid fibril formation process using sonicated mature amyloid fibrils accelerates the fibril formation process efficiently, however, addition of intact full-length lysozyme at the end of the lag phase slows the rate of amyloidogenesis. The intact full-length protein, in contrast to nicked lysozyme, slows fibril formation due to its slow conversion into the amyloid fold, probably due to inclusion of the non-amyloidogenic 1-48/102-129 portion of HEWL in the fibrils, which can function as a "molecular bumper" stalling further growth. © 2006 Elsevier Ltd. All rights reserved.

  • 67.
    Monstein, Hans-Jurg
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Balkhed Östholm, Åse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Nilsson, MV
    Nilsson, M
    Dornbusch, Kathrine
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Multiplex PCR amplification assay for the detection of blaSHV, blaTEM and blaCTX-M genes in Enterobacteriaceae2007In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, no 12, p. 1400-1408Article in journal (Refereed)
    Abstract [en]

    Extended-spectrum β-lactamases (ESBLs) are often mediated by bla-SHV, blaTEM and blaCTX-M genes in Enterobacteriaceae and other Gram-negative bacteria. Numerous molecular typing methods, including PCR-based assays, have been developed for their identification. To reduce the number of PCR amplifications needed we have developed a multiplex PCR assay which detects and discriminates between bla-SHV, blaTEM and blaCTX-M PCR amplicons of 747, 445 and 593 bp, respectively. This multiplex PCR assay allowed the identification of bla-SHV, blaTEM and blaCTX-M genes in a series of clinical isolates of Enterobacteriaceae with previously characterised ESBL phenotype. The presence of blaSHV, blaTEM and blaCTX-M genes was confirmed by partial DNA sequence analysis. Apparently, the universal well-established CTX-M primer pair used here to reveal plasmid-encoded blaCTX-M genes would also amplify the chromosomally located K-1 enzyme gene in all Klebsiella oxytoca strains included in the study.

  • 68.
    Monstein, Hans-Jurg
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Grahn, Niclas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ohlsson, Bodil
    Proenkephalin-A mRNA is widely expressed in tissues of the human gastrointestinal tract2006In: European Surgical Research, ISSN 0014-312X, E-ISSN 1421-9921, Vol. 38, no 5, p. 464-468Article in journal (Refereed)
    Abstract [en]

    Background: It has been shown that the non-opioid effects of Met-enkephalin, which is derived from proenkephalin-A, are mediated through a specific opioid growth factor (OGF) receptor which is assumed to be involved in the control of cell growth. The expression and tissue location of proenkephalin-A mRNA in the gastrointestinal tract remains largely unknown. Methods: In this study we have analyzed the expression of proenkephalin-A mRNA in the human esophagus, gastrointestinal tract and surrounding organs by means of reverse-transcriptase PCR (RT-PCR). Results: The present study demonstrates proenkephalin-A mRNA expression in the human esophagus, gastrointestinal tract, pancreas, and gallbladder. Conclusion: The present study demonstrates proenkephalin-A mRNA expression in regions of the human esophagus, gastrointestinal tract, pancreas, and gallbladder tissues which provides information for the future mapping of proenkephalin-A mRNA and protein expression/co-expression at the cellular level. Copyright © 2006 S. Karger AG.

  • 69.
    Monstein, Hans-Jurg
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Grahn, Niclas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Truedsson, Mikael
    Ohlsson, Bodil
    Progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA expression in non-tumor tissues of the human gastrointestinal tract2006In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 12, no 16, p. 2574-2578Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate the expression of gastrin-releasing peptide (GRP) and GRP-receptor mRNA in non-tumor tissues of the human esophagus, gastrointestinal tract, pancreas and gallbladder using molecular biology techniques. Methods: Poly A+ mRNA was isolated from total RNA extracts using an automated nucleic acid extractor and, subsequently, converted into single-stranded cDNA (ss-cDNA). PCR amplifications were carried out using gene-specific GRP and GRP-receptor primers. The specificity of the PCR amplicons was further confirmed by Southern blot analyses using gene-specific GRP and GRP-receptor hybridization probes. Results: Expre ssion of GRP and GRP-receptor mRNA was detected at various levels in nearly all segments of the non-tumor specimens analysed, except the gallbladder. In most of the biopsy specimens, co-expression of both GRP and GRP-receptor mRNA appeared to take place. However, expression of GRP mRNA was more prominent than was GRP-receptor mRNA. Conclusion: GRP and GRP-receptor mRNAs are expressed throughout the gastrointestinal tract and provides information for the future mapping and determination of its physiological importance in normal and tumor cells. © 2006 The WJG Press. All rights reserved.

  • 70.
    Monstein, Hans-Jurg
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Olsson, Crister
    Nilsson, Isabelle
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Grahn, Niclas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Benoni, Cecilia
    Ahrné, Siv
    Multiple displacement amplification of DNA from human colon and rectum biopsies: Bacterial profiling and identification of Helicobacter pylori-DNA by means of 16S rDNA-based TTGE and pyrosequencing analysis2005In: Journal of Microbiological Methods, ISSN 0167-7012, E-ISSN 1872-8359, Vol. 63, no 3, p. 239-247Article in journal (Refereed)
    Abstract [en]

    Amplifying bacterial DNA by PCR from human biopsy specimens has sometimes proved to be difficult, mainly due to the low amount of bacterial DNA present. Therefore, nested or semi-nested 16S rDNA PCR amplification has been the method of choice. In this study, we evaluate the potential use of whole genome amplification of total DNA isolated from human colon and rectum biopsy specimens, followed by 16S rDNA PCR amplification of multiple displacement amplified (MDA)-DNA. Subsequently, a H. pylori-specific 16S rDNA variable V3 region PCR assay was applied directly on MDA-DNA and, combined with pyrosequencing analysis, the presence of H. pylori in some biopsies from colon in patients with microscopic colitis was confirmed. Furthermore, temporal temperature gradient gel electrophoresis (TTGE) of 16S rDNA amplicons using primers flanking variable regions V3, V4, and V9, was used to establish bacterial profiles from individual biopsies. A variation of the bacterial profiles in the colonic mucosa in microscopic colitis and in normal rectal mucosa was observed. In conclusion we find the MDA technique to be a useful method to overcome the problem of insufficient bacterial DNA in human biopsy specimens. © 2005 Elsevier B.V. All rights reserved.

  • 71. Monstein, Hans-Jürg
    et al.
    Fransén, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Dimberg, Jan
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    K-ras and B-raf gene mutations are not associated with gastrin- and CCK2-receptor mRNA expression in human colorectal tumour tissues2004In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 34, no 2, p. 100-106Article in journal (Refereed)
    Abstract [en]

    Background: Colorectal cancer is a multistep process caused by genetic alterations in cell growth regulatory genes such as K-ras and B-raf. It has been assumed that mutations in the K-ras gene induce gastrin gene expression and that gastrin stimulates the growth of colorectal cancer in an autocrine fashion by coexpressing gastrin and cholecystokinin (CCK)2 receptors. The aim of this study was to examine a possible association of K-ras and B-raf gene mutations with gastrin and CCK2 receptor mRNA expression in human colon and rectum tumour biopsy specimens. Methods: K-ras and B-raf gene mutations as well as gastrin and CCK2 receptor mRNA expression in 50 colon and 46 rectum biopsies, respectively, were determined using molecular biology methods. Results: K-ras mutations occurred in 44% colon and 30% rectum and B-raf mutations in 16% colon and 4% rectum tumours, respectively. Gastrin mRNA was expressed in 64% colon and 61% rectum tumours, whereas CCK2 receptor mRNAs was expressed in 32% colon and 13% rectum tumours. K-ras or B-raf gene mutations and simultaneous gastrin mRNA expression was observed in 40% colon and 17% rectum tumours, respectively. Coexpression of gastrin and CCK2 receptor mRNA occurred in 20% colon and 9% rectal tumours. Conclusions: The results do not support the hypothesis that K-ras and B-raf gene mutations have an impact on gastrin- and CCK-receptor mRNA expression in colorectal tumour tissues.

  • 72.
    Naidu-Sjöswärd, Kerstin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Mounira, H
    Davidsson, Anette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Schmekel, Birgitta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Single-isomer R-salbutamol is not superior to racemate regarding protection for bronchial hyperresponsiveness2004In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 98, no 10, p. 990-Article in journal (Refereed)
    Abstract [en]

    Bronchial hyper-reactivity (BHR) has been suggested to follow cessation of regular medication with racemic salbutamol. This study aimed at investigating the effects from medication with R,S- and R-salbutamol on bronchial response to provocation with isocapnic hyperventilation of cold air (IHCA). Twenty-six patients with mild to moderate asthma were enrolled in a double-blind, randomised, cross-over study. Bronchial response to provocation was measured before and after 1 week's medication. Doses of 0.63 mg R-salbutamol or 1.25 mg R/S-salbutamol were inhaled three times daily during medication-weeks and a wash-out week intervened. Tests were performed 6 h after the last dose of test drug. Impulse oscillometry and forced expiratory volume during one second were methods used to identify bronchial response to provocation. Two patients withdrew from the investigation due to side-effects, one from R- the other from R,S-salbutamol. Comparable resting bronchial conditions were indicated by differences in baseline lung function values of <2% between study days. No statistically significant medication-dependent differences in BHR could be demonstrated between treatment groups. However, 15 patients exhibited higher (P=0.03) post-treatment BHR after pure R-salbutamol than after R,S-salbutamol. Furthermore, plasma concentrations of R-salbutamol tended to be lower (P=0.08) after medication with R- than after R,S-salbutamol despite equal doses of R-salbutamol given during the two separate treatment periods. We also found that considerable amounts of S-salbutamol were retrieved in plasma after medication with pure R-salbutamol. We conclude that we were unable to demonstrate favourable effects of R-salbutamol over R,S-salbutamol regarding response to provocation with IHCA after regular medication of 1 week's duration.

  • 73. Nielsen, J.B
    et al.
    Ekstrand, Jimmy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology.
    Zalups, R.K
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Inheritance of susceptibility: mercury kinetics in two mouse strains (A.SW and B10.S) and their F1 generation.2006In: Metal ions in biological systems, ISSN 0161-5149, E-ISSN 2154-9214, Vol. 9, p. 351-355Article in journal (Refereed)
    Abstract [en]

       

  • 74.
    Nilsson, Isabelle
    et al.
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Shabo, Ivan
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Svanvik, Joar
    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.
    Monstein, Hans-Jurg
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Multiple displacement amplification of isolated DNA from human gallstones: Molecular identification of Helicobacter DNA by means of 16S rDNA-based pyrosequencing analysis2005In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 10, no 6, p. 592-600Article in journal (Refereed)
    Abstract [en]

    Background. Molecular typing of Helicobacter spp. in clinical biopsy specimens has become increasingly important. By means of nested polymerase chain reaction (PCR) amplification and Southern blot analysis of the PCR amplicons, we have shown that Helicobacter spp. DNA is present in human gallstones. In this study we have investigated the possibility of using multiple displacement amplification (MDA) of isolated gallstone DNA and pyrosequencing analysis for the molecular identification of Helicobacter spp. Materials and Methods. DNA isolated from the nucleus of 33 human gallstones and one control strain were used in a MDA assay. Subsequently, pyrosequencing analysis was performed either directly on MDA-DNA using primers flanking the Helicobacter spp. 16S rDNA variable V3 region or on PCR amplicons derived from broad-range primers flanking the 16S rDNA variable V3, V4, and V9 regions. Results. Pyrosequencing analysis of 16S rDNA derived from MDA-DNA revealed that Helicobacter spp.-like DNA was present in 25 of 33 (approximately 76%) gallstones. Using an H. pylori-specific Southern blot analysis, Helicobacter spp.-like DNA was present in 20 of 33 [approximately 61%] of the gallstones. Using MDA-DNA directly in pyrosequencing analysis, Helicobacter spp.-like DNA was present in 13 of 33 [approximately 39%] gallstones. Conclusions. We conclude that multiple displacement amplification combined with pyrosequencing enables a rapid and accurate molecular typing of Helicobacter spp. from small and precious biopsy specimens. © 2005 The Authors Journal compilation © 2005 Blackwell Publishing Ltd.

  • 75. Nilsson, Joacim
    et al.
    Söderberg, Ola
    Nilsson, Kenneth
    Rosén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Differentiation-associated redox-regulation in human B cell lines from stem cell/pro-B to plasma cell2004In: Immunology Letters, ISSN 0165-2478, E-ISSN 1879-0542, Vol. 94, no 1-2, p. 83-89Article in journal (Refereed)
    Abstract [en]

    Redox-regulation of receptors and transcription factors are important for lymphocyte activation, differentiation and apoptosis. Thioredoxin (Trx) is a key redox-regulating protein and oxidative stress sensor operating in synergy with Trx-reductase and protein disulfide isomerase (PDI). The expression of Trx, PDI, and the Trx-regulated transcription-factor Pax5 were analyzed in a panel of human B cell lines and were compared with that of the Bcl-2 family proteins, also redox-controlled. The panel included representative cells from various stages: FLEB14-4 (pro-B), REH and NALM-6 (pre-B), Rael and Daudi (small mature B), U-698 and NC0467.3 (B-blasts), LP-1, U-1996, and U-266 (plasma cells). We found a significant congruence and co-variation of Trx and Bcl-2 levels in the B-lineage, with high expression levels in early stages (pro-B and pre-B) and in the late stage representing terminally-differentiated plasma cells, whereas mid-stage small resting B cells showed a very low expression. PDI increased significantly in plasma-blasts and plasma cells, indicating its importance in the highly specialized immunoglobulin assembly-machinery, including disulfide-bond isomerization. Pax5 was expressed in early and mid-stages, but was silenced in terminal stages. We conclude that the high Trx and Bcl-2-expression early and late in the B cell maturation pathway reflects a redox-strategy favoring an increased survival potential of the B cells at those stages. © 2004 Elsevier B.V. All rights reserved.

  • 76. Nilsson, Maria
    et al.
    Wang, Xin
    Rodziewicz-Motowidlo, Sylwia
    Janowski, Robert
    Lindström, Veronica
    Önnerfjord, Patrik
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Grzonka, Zbigniew
    Jaskolski, Mariusz
    Grubb, Anders
    Prevention of domain swapping inhibits dimerization and amyloid fibril formation of cystatin C2004In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 279, p. 24236-24245Article in journal (Refereed)
  • 77.
    Nilsson, Peter
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics .
    Hammarström, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Ahlgren, Fredrik
    Division of Cell Biology Linköpings universitet.
    Herland, Anna
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics .
    Schnell, Edrun A
    The Norwegian University of Science and Technology.
    Lindgren, Mikael
    The Norwegian University of Science and Technology.
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Inganäs, Olle
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics .
    Conjugated Polyelectrolytes - Conformation - Sensitive Optical Probes for staining and Characterization of Amyloid Deposits2006In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 7, p. 1096-1104Article in journal (Refereed)
    Abstract [en]

      

  • 78.
    Nilsson, Peter
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Åslund, Andreas
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry.
    Berg, Ina
    Nyström, Sofie
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Konradsson, Peter
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry.
    Herland, Anna
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics.
    Inganäs, Olle
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics.
    Stabo-Eeg, Frantz
    Lindgren, Mikael
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Lannfelt, Lars
    Nilsson, Lars N G
    Hammarström, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes2007In: ACS Chemical Biology, ISSN 1554-8929, Vol. 2, no 8, p. 553-560Article in journal (Refereed)
    Abstract [en]

    Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.

  • 79.
    Palmebäck Wegman, Pia
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Wingren, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    CYP2D6 variants and the prediction of tamoxifen response in randomized patients: authors' response2005In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 7, no 6, p. 234-234Article in journal (Refereed)
  • 80.
    Paulsson, Johan
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Andersson, A.
    Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
    Westermark, P.
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Westermark, Gunilla
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Intracellular amyloid-like deposits contain unprocessed pro-islet amyloid polypeptide (proIAPP) in beta cells of transgenic mice overexpressing the gene for human IAPP and transplanted human islets2006In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, no 6, p. 1237-1246Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Islet amyloid is a frequent finding in the islets of Langerhans of individuals with type 2 diabetes. The main amyloid constituent is the beta cell-derived polypeptide hormone islet amyloid polypeptide (IAPP). In general, amyloid refers to an extracellular deposit of a congophilic material, but intracellular amyloid is seen in some beta cells of transgenic mice expressing the gene for human IAPP and in human islets transplanted into nude mice. The aim of this study was to immunohistochemically characterise the intracellular amyloid. Methods: Antisera against the N- and C-terminal processing sites of proIAPP (which were therefore specific for proIAPP), the C-terminal flanking peptide and mature IAPP were used for immunoelectron microscopy. Results: Fibrillar aggregates were seen in the halo region of the secretory granules in some beta cells in human IAPP transgenic mice. These aggregates were labelled with proIAPP-specific antisera. Also, proIAPP reactivity was more widespread in the intracellular amyloid-like aggregates in beta cells of transgenic mice than in human islet transplants, in which the intracellular amyloid-like deposits were larger, but the proIAPP labelling was restricted to small spots within the amyloid deposits. Conclusions/ interpretation: We suggest that proIAPP forms the first amyloid fibrils and that this can occur already in the secretory granules of the beta cells. The proIAPP-derived fibrils can act as seed for further amyloid formation, now made up by IAPP. The observed difference between human islet transplants and human IAPP transgenic animals may reflect differences in stages of amyloid development. © Springer-Verlag 2006.

  • 81.
    Paulsson, Johan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Aberrant processing of human proislet amyloid polypeptide results in increased amyloid formation2005In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 54, no 7, p. 2117-2125Article in journal (Refereed)
    Abstract [en]

    The amyloid present in the islets of Langerhans in type 2 diabetes is polymerized islet amyloid polypeptide (IAPP). The precursor protein proIAPP is posttranslationally modified, a process involving the removal of NH2- and COOH-terminal flanking peptides. This step is performed by the prohormone convertases PC2 and PC1/3. PC2 processes proIAPP preferably at the NH 2-terminal processing site, and PC1/3 processes proIAPP exclusively at the COOH-terminal site. Little is known regarding the exact circumstances leading to islet amyloid formation. In this study, we have examined the possible significance of aberrant processing of proIAPP on amyloid formation in several in vitro cellular systems. In our studies, human (h)-proIAPP was transfected into β-TC-6 cells expressing both prohormone convertases and in which proIAPP is processed into IAPP. Additionally, h-proIAPP was transfected into three different pituitary-derived cell lines with different prohormone convertase profiles: AtT-20 cells (deficient in PC2), GH3 cells (deficient in PC1/3), and GH4C1 cells (deficient in both convertases). We followed the processing of h-proIAPP with antibodies specific for the respective cleavage sites and stained the cells with Congo red to verify the accumulation of amyloid. Incomplete processing of h-proIAPP that occurs in AtT-20 and GH4C1 cells resulted in the formation of intracellular amyloid. No amyloid developed in β-TC-6 and GH3 cells lines with full processing of proIAPP. An intracellular increase in proIAPP and/or its metabolic products may thus promote intracellular amyloid formation, thereby causing cell death. When extracellularly exposed, this amyloid might act as template for continuing amyloid formation from processed IAPP released from the surrounding β-cells. © 2005 by the American Diabetes Association.

  • 82.
    Ruud, Johan
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Blomqvist, Anders
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Identification of rat brainstem neuronal structures activated during cancer-induced anorexia2007In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 504, no 3, p. 275-286Article in journal (Refereed)
    Abstract [en]

    In cancer-related anorexia, body weight loss is paradoxically associated with reduced appetite, which is contrary to the situation during starvation, implying that the normal coupling of food intake to energy expenditure is disarranged. Here we examined brainstem mechanisms that may underlie suppression of food intake in a rat model of cancer anorexia. Cultured Morris 7777 hepatoma cells were injected subcutaneously in Buffalo rats, resulting in slowly growing tumor and reduced food intake and body weight loss after about 10 days. The brainstem was examined for induced expression of the transcription factors Fos and FosB as signs of neuronal activation. The results showed that anorexia and retarded body weight growth were associated with Fos protein expression in the area postrema, the general visceral region of the nucleus of the solitary tract, and the external lateral parabrachial nucleus, structures that also display Fos after peripheral administration of satiating or anorexigenic stimuli. The magnitude of the Fos expression was specifically related to the size of induced tumor, and not associated with weight loss per se, because it was not present in pair-fed or food-deprived rats. It also appeared to be independent of proinflammatory cytokines, as determined by the absence of increased cytokine levels in plasma and induced cytokine and cyclooxygenase expression in the brain. The findings thus provide evidence that cancer-associated anorexia and weight loss in this model is associated with activation of brainstem circuits involved in the suppression of food intake, and suggest that this occurs by inflammatory-independent mechanisms. © 2007 Wiley-Liss, Inc.

  • 83. Saha, Sipra
    et al.
    Engström, Linda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Mackerlova, Ludmila
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Jakobsson, Per-Johan
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Impaired febrile responses to immune challenge in mice deficient in microsomal prostaglandin E synthase-12005In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 288, no 5 57-5Article in journal (Refereed)
    Abstract [en]

    Fever is a common, centrally elicited sign of inflammatory and infectious processes and is known to be induced by the action of PGE2 on its specific receptors in the thermogenic region of the hypothalamus. In the present work, using genetically modified mice, we examined the role of the inducible terminal PGE2-synthesizing enzyme microsomal prostaglandin E synthase-1 (mPGES-1) for the generation of immune-elicited fever. Animals with a deletion of the Ptges gene, which encodes mPGES-1, or their wild-type littermates were given either a subcutaneous injection of turpentine-a model for aseptic cytokine-induced pyresis-or an intraperitoneal injection of interleukin-1β. While both procedures resulted in typical febrile responses in wild-type animals, these responses were strongly impaired in the mPGES-1 mutant mice. In contrast, both genotypes showed psychogenic stress-induced hyperthermia and displayed normal diurnal temperature variations. Both wild-type and mPGES-1 mutant mice also showed strongly reduced motor activity following turpentine injection. Taken together with previous observations on mPGES-1 induction in the brain vasculature during various inflammatory conditions and its role in endotoxin-induced pyresis, the present findings indicate that central PGE 2 synthesis by mPGES-1 is a general and critical mechanism for fever during infectious and inflammatory conditions that is distinct from the mechanism(s) underlying the circadian temperature regulation and stress-induced hyperthermia, as well as the inflammation-induced activity depression. Copyright © 2005 the American Physiological Society.

  • 84.
    Schultz-Lampel, Daniela
    et al.
    Department of Adult Pediatric Urology University of Witten.
    Jiang, Chonghe
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Lindström, Sivert
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Joachim W, Thüroff
    Department of Urology, School of Medicine, Mainz Germany.
    Experimental results on mechanisms of action of electrical neuromodulation in chronical urinary retention1998In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 16, no 5, World J Urol, p. 301-304Article in journal (Refereed)
    Abstract [en]

     Sacral foramen neuromodulation--initially applied for the treatment of urinary incontinence--has proved to be effective in patients with chronic urinary retention. Thus far, the underlying neurophysiological mechanisms have not been elucidated. In an experimental study on the neurophysiological basis of sacral neurostimulation, one objective was to investigate the mechanisms responsible for initiation of micturition in chronic urinary retention. In ten female cats anesthetized with alpha-chloralose the clinical situation of sacral foramen stimulation was experimentally reproduced by isolated S2 nerve stimulation after L6-S3 laminectomy. Stimulation responses were recorded from the bladder, peripheral nerves, and striated muscles of the foot and pelvic floor. The effect of sudden cessation of prolonged S2 stimulation, during which the bladder was completely inhibited, was evaluated in 70 stimulation sequences in 5 cats. Sacral nerve stimulation induced excitatory and inhibitory effects on the bladder, depending on the frequency and intensity of stimulation. With unilateral S2 stimulation, bladder excitation was best at frequencies of 2-5 Hz and at intensities ranging between 0.8 and 1.4 times the threshold for the M-response of the foot muscle. Inhibition was the dominating effect at frequencies of 7-10 Hz and at intensities exceeding 1.4 times the threshold. Prolonged S2 stimulation above the threshold produced complete bladder inhibition during stimulation but induced strong bladder contractions after sudden interruption of stimulation, with amplitudes being significantly higher than that of spontaneous contractions preceding the stimulation. These results confirm the hypothesis of a "rebound" phenomenon as the mechanism of action for induction of spontaneous voiding in patients with chronic urinary retention.

  • 85. Schölin, A
    et al.
    Björklund, L
    Borg, H
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Björk, E
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Gudbjörnsdottir, S
    Nyström, L
    Östman, J
    Karlsson, AF
    Sundkvist, G
    Islet antibodies and remaining β-cell function 8 years after diagnosis of diabetes in young adults: A prospective follow-up of the nationwide Diabetes Incidence Study in Sweden2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 255, no 3, p. 384-391Article in journal (Refereed)
    Abstract [en]

    Objectives. To establish the prevalence of remaining β-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. Design. Population-based cohort study. Setting. Nationwide from all Departments of Medicine and Endocrinology in Sweden. Subjects. A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. Main outcome measure. Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved β-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies -were measured. Results. Amongst 269 islet antibody positives (ab+) at diagnosis, preserved β-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2,respectively, P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively, P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively, P = 0.007) at diagnosis compared with ab+ without remaining β-cell function. Amongst the 241 patients without detectable β-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. Conclusions. Sixteen per cent of patients with autoimmune type 1 diabetes had remaining β-cell function 8 years after diagnosis whereas 5.8% with β-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.

  • 86. Schölin, A
    et al.
    Törn, C
    Nyström, L
    Berne, C
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Kockum, I
    Landin-Olsson, M
    Östman, J
    Karlsson, FA
    Sundkvist, G
    Björk, E
    Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes2004In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 21, no 5, p. 447-455Article in journal (Refereed)
    Abstract [en]

    Aim: To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM). Methods: In Sweden, 362 patients (15-34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA1c and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose ≤ 0.3 U/kg/24 h and HbA1c within the normal range, was analysed in relation to characteristics at diagnosis. Results: Remissions were seen in 43% of the patients with a median duration of 8 months (range 1-73). Sixteen per cent had a remission with a duration > 12 months. Among patients with antibodies (ab+), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20-24.9 kg/m2) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab+ remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions. Conclusion: In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.

  • 87. Song, Jikiu
    et al.
    Lee, Min S
    Carlberg, Inger
    Vener, Alexander
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Markley, John L
    Micelle-induced folding of spinach thylakoid soluble phosphoprotein of 9 kDa and its functional implications2006In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 45, no 51, p. 15633-15643Article in journal (Refereed)
    Abstract [en]

    Thylakoid soluble phosphoprotein of 9 kDa (TSP9) has been identified as a plant-specific protein in the photosynthetic thylakoid membrane (Carlberg et al. (2003) Proc. Natl. Acad. Sci. 100, 757-762). Nonphosphorylated TSP9 is associated with the membrane, whereas, after light-induced phosphorylation, a fraction of the phosphorylated TSP9 is released into the aqueous stroma. By NMR spectroscopy, we have determined the structural features of nonphosphorylated TSP9 both in aqueous solution and in membrane mimetic micelles. The results show that both wild type nonphosphorylated TSP9 and a triple-mutant (T46E + T53E + T60E) mimic of the triphosphorylated form of TSP9 are disordered under aqueous conditions, but adopt an ordered conformation in the presence of detergent micelles. The micelle-induced structural features, which are similar in micelles either of SDS or dodecylphosphocholine (DPC), consist of an N-terminal α-helix, which may represent the primary site of interaction between TSP9 and binding partners, and a less structured helical turn near the C-terminus. These structured elements contain mainly hydrophobic residues. NMR relaxation data for nonphosphorylated TSP9 in SDS micelles indicated that the molecule is highly flexible with the highest order in the N-terminal α-helix. Intermolecular NOE signals, as well as spin probe-induced broadening of NMR signals, demonstrated that the SDS micelles contact both the structured and a portion of the unstructured regions of TSP9, in particular, those containing the three phosphorylation sites (T46, T53, and T60). This interaction may explain the selective dissociation of phosphorylated TSP9 from the membrane. Our study presents a structural model for the role played by the structured and unstructured regions of TSP9 in its membrane association and biological function. © 2006 American Chemical Society.

  • 88.
    Spetea Wiklund, Cornelia
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Molecular genetics. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Thuswaldner, Sophie
    Update in nucleotide-dependent processes in plant chloroplasts2008In: Plant Cell Compartments - Selected Topics / [ed] Benoît Schoefs, Kerala, India: Research Signpost , 2008, p. 104-149Chapter in book (Other academic)
    Abstract [en]

       Membranes separate the interior medium from the exterior. Obviously, separation does not mean isolation and the membranes, as we can see them at present, act as selective filters across which different types of compounds such as salts, waste, nutriments, nucleotides, etc are transported. Depending on the molecule to be transported several ways can be used. How nucleotides are transported through the thylakoid membranes to the lumen and used in the chloroplast is the aim of the chapter by Drs. Spetea and Thuswaldner, while that of Drs. Paulilo and Falkenkrog reviews the composition of nuclear pores that mediate all the traffic between the nucleus and cytoplasm. In which ways, during evolution, the first cells were formed and how the different compartments appeared remain as tremendously exciting questions, but so far unsolved in many cases. Several theories have been proposed.

    The best known is that proposed by Margulis (1970), according to which an ancestral anaerobic prokaryote would become able to ingest solid particles such as other prokaryotes. In some cases the ingested bacteria continued to live and have evolved to give different types of membranes that eukaryotic cells contain today. This theory, also called the endosymbiotic theory, explains the origin of both the chloroplasts and the mitochondria, two major organelles of plant cells. More recently, another symbiotic theory has been proposed by Martin and Müller (1998) to explain the origin of mitochondria. While the contribution by Dr. Bizanz and collaborators traces back the unexpected fate of plastids in today's prokaryotic parasites of animal cells, the chapters by Drs. Solymosi and Schoefs, Dr. Chamarovsky and collaborators and, Dr. Rohacek and collaborators are dedicated to the biogenesis and functioning of the chloroplast membranes. The way of differentiation of the other organelles and cell compartments remain so far as unanswered questions. The search for analoguous compartments in lower organisms may provide the first elements of an answer.

    the chapter by Dr. H. Guo enters in this frame and offers a good example for the existence of a putative, so far unrevealed compartment analogue to the higher plant vacuole in cyanobacteria. The plant cell turgor is maintained thanks to the functioning of two typical compartments of plant cells i.e. the cell-wall and the vacuole, but these compartments play other important roles in plant physiology. The chapters by Dr. El Gharras and Dr. Martinez on the accumulation of betalain pigments in vacuoles and strawberry cell-wall softening, respectively, illustrate these aspects of the field. Even if plant cells are surrounded by a thick and rigid cell-wall, their interior is highly dynamic: the organelles are able to move. The contribution by Dr. Foissner analyzes the dynamic of mitochondria in Chara internodal cells. In contrast to animals, plants cannot escape from adverse conditions. Consequently, they have developed strategies to survive to biotic or/and abiotic stresses.

    In this book the description of the answers of plants to several stresses are the aim of some chapters. While the contribution by Dr. Ben Khaled and collaborators reports on the peroxidase activity in palm plantlets inoculated with arbuscular mycorrhiza fungi in the presence of biocontrol agents, the chapter by Dr. Dumas-Gaudot and collaborators, describes the modifications in the protein composition occuring during the differentiation of the arbuscules. The formation of the arbuscule is accompanied by a redistribution of the colonized root cell organelles around the arbuscule and by a dramatic change in the plastid metabolism allowing them to produce secondary metabolites, including secondary carotenoid and apocarotenoid molecules (chapter by Dr. Fester). Abiotic stresses, such as nitrogen deficiency, are also able to trigger the production of secondary carotenoids. Dr. Lemoine and collaborators review such a strategy in green algae. Because secondary carotenoids are usually high added value compounds, the knowledge about the functioning of the different compartments in such a production is also of great importance for the economic side of plant science s.l.

    How chloroplasts cope with heavy metals is discussed in the chapter by Dr. Poirier and collaborators. During the last years, new technical tools such as confocal imaging became more popular. Their use revealed the presence of new compartments, sometimes being divided into subtle sub-compartments. The intention of this book is to bring together a serie of outstanding contributions dealing with the biosynthesis, content, distribution, function, and physiology of various plant cell compartments. By combining the major contributions in this book, I wished to contribute to the propagation of the recent developments in plant cell biochemistry and physiology, to the discovery of the wonderful plant world and, also, to mutual exchange of ideas. Without the excellent work of the different authors, who have taken great care to present an up-to-date review of their field and 'Research Signpost' as the commercial editor, this book could not have been produced. I wish to dedicate this book to the different mentors in Belgium, Czech Republic and France, who showed me the scientific way and, also to my wife for her everlasting support to me.

  • 89.
    Stadig Degerman, Mari
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    Tibell, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Bernhard, Jonte
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    University Teachers View about Learning Metabolism - What are the core knowledge and which are the Students' Difficulties?2007In: ESERA,2007, 2007Conference paper (Refereed)
  • 90.
    Stening, Kent
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Eriksson, Olle
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Arts and Sciences.
    Wahren, Lis Karin
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Hammar, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Pain sensations to the cold pressor test in normally menstruating women: Comparison with men and relation to menstrual phase and serum sex steroid levels2007In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 293, no 4Article in journal (Refereed)
    Abstract [en]

    The role of gonadal hormones on pain sensations was investigated in normally menstruating women (n = 16) using the cold pressor test. Tolerance time, pain threshold, and pain intensity were examined once a week during a 4-wk period, and serum concentrations of 17β-estradiol and progesterone were determined at each test session, which were classified into the early follicular phase, late follicular phase, early luteal phase, and late luteal phase, as determined by the first day of menses and the actual hormone levels recorded. A group of men (n = 10) of the same age interval was examined for comparison. The data show that pain threshold was reduced during the late luteal phase compared with the late follicular phase, and hormone analyses showed significant positive correlation between the progesterone concentration and lowered pain threshold and increasing pain intensity. Hormone analysis also showed an interaction between S-estradiol and S-progesterone on pain intensity, demonstrating that the increased perceived pain intensity that was associated with high progesterone concentrations was significantly reduced with increasing levels of estradiol. While no statistically significant sex differences in pain measurements were found, women displayed much more pronounced, and statistically significant, session-to-session effects than men, with increased pain threshold and decreased pain intensity with each test session. Hence, these data suggest that the changes in the serum concentration of gonadal hormones that occur during the menstrual cycle influence pain sensations elicited by noxious tonic cold stimulation and show that adaptation to the cold pressor test may be sex dependent. © 2007 the American Physiological Society.

  • 91.
    Strålfors, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Insulin signaling and caveolae2005In: Caveolae and lipid rafts: roles in signal transduction and the pathogenesis of human disease / [ed] Carolyn E. Patterson, San Diego: Elevier Academic Press , 2005, 1, p. 141-169Chapter in book (Other academic)
    Abstract [en]

    This readable, comprehensive text covers endothelial biology from the fundamentals of structure and lung fluid balance physiology to state-of-the-art descriptions of the molecular mechanisms involved in the development of lung failure. The material and illustrations, provided by outstanding experts in their individual areas of research and clinical concentration, is artfully woven together to provide the reader with an integrated, in-depth, and up-to-date knowledge of endothelial function, vascular integrity, pulmonary function, and pathophysiology in respiratory failurec

  • 92.
    Strålfors, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Insulinets verkningsmekanism och insulinresistens vid typ 2 diabetes2005In: Incitament, ISSN 1103-503X, no 7, p. 536-538Article in journal (Refereed)
  • 93. Ståhl, Annelie
    et al.
    Nilsson, Stefan
    Lundberg, Pontus
    Bhushan, Shashi
    Biverståhl, Henrik
    Moberg, Per
    Morisset, Magali
    Vener, Alexander
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Mäler, Lena
    Langel, Ulo
    Glaser, Elzbieta
    Two novel targeting peptide degrading proteases, PrePs, in mitochondria and chloroplasts, so similar and still different2005In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 349, no 4, p. 847-860Article in journal (Refereed)
    Abstract [en]

    Two novel metalloproteases from Arabidopsis thaliana, termed AtPrePI and AtPrePII, were recently identified and shown to degrade targeting peptides in mitochondria and chloroplasts using an ambiguous targeting peptide. AtPrePI and AtPrePII are classified as dually targeted proteins as they are targeted to both mitochondria and chloroplasts. Both proteases harbour an inverted metal binding motif and belong to the pitrilysin subfamily A. Here we have investigated the subsite specificity of AtPrePI and AtPrePII by studying their proteolytic activity against the mitochondrial F1β pre-sequence, peptides derived from the F1β pre-sequence as well as non-mitochondrial peptides and proteins. The degradation products were analysed, identified by MALDI-TOF spectrometry and superimposed on the 3D structure of the F 1β pre-sequence. AtPrePI and AtPrePII cleaved peptides that are in the range of 10 to 65 amino acid residues, whereas folded or longer unfolded peptides and small proteins were not degraded. Both proteases showed preference for basic amino acids in the P1 position and small, uncharged amino acids or serine residues in the P′1 position. Interestingly, both AtPrePI and AtPrePII cleaved almost exclusively towards the ends of the α-helical elements of the F1β pre-sequence. However, AtPrePI showed a preference for the N-terminal amphiphilic α-helix and positively charged amino acid residues and degraded the F1β pre-sequence into 10-16 amino acid fragments, whereas AtPrePII did not show any positional preference and degraded the F1β pre-sequence into 10-23 amino acid fragments. In conclusion, despite the high sequence identity between AtPrePI and AtPrePII and similarities in cleavage specificities, cleavage site recognition differs for both proteases and is context and structure dependent. © 2005 Elsevier Ltd. All rights reserved.

  • 94.
    Sun, Xiao-Feng
    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.
    Ahmadi, Ahmad
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Arbman, Gunnar
    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.
    Wallin, Åsa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Asklid, Daniel
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Polymorphisms in sulfotransferase 1A1 and glutathione S-transferase P1 genes in relation to colorectal cancer risk and patients' survival2005In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 11, no 43, p. 6875-6879Article in journal (Refereed)
    Abstract [en]

    Aim: To examine whether polymorphisms in SULT1A1 and GSTP1 genes contribute to colorectal cancer development and whether they are associated with clinicopathological variables are not well identified. Methods: We examined the genotypes of 125 colorectal cancer patients and 666 healthy controls in a Swedish population by using PCR restriction fragment length polymorphism (RFLP). Results: SULT1A1 *2/*2 genotype (OR = 2.49, 95%CI = 1.48-4.19, P = 0.0002) and *2 allele (OR = 1.56, 95%CI = 1.16-2.10, P = 0.002) had an effect on colorectal cancer susceptibility, while GSTP1 genotype was without effect. However, GSTP1 G-type predicted a worse prognosis in the patients independently of gender, age, Dukes' stage, growth pattern, and differentiation (P = 0.03). Conclusion: Polymorphism in SULT1A1 may predispose to colorectal cancer and GSTP1 may be a biological indicator of prognosis in the patients. © 2005 The WJG Press and Elsevier Inc. All rights reserved.

  • 95.
    Sun, Yi-Qian
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Monstein, Hans-Jurg
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Ryberg, Anna
    Borch, Kurt
    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.
    Multiple strand displacement amplification of DNA isolated from human archival plasma/serum: Identification of cytokine polymorphism by pyrosequencing analysis2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 377, no 1-2, p. 108-113Article in journal (Refereed)
    Abstract [en]

    Background: DNA isolation from formalin-fixed paraffin-embedded tissue appears to be problematic due to degradation caused by fixative. Our aim was to investigate if the isolated genomic DNA from archival plasma/serum, combined with multiple strand displacement amplification (MDA) can be used for genotyping. Methods: Nine archival plasma/serum samples and freshly frozen gastric biopsies from the same nine H. pylori-infected subjects were used for DNA isolation. Subsequently, MDA-DNA derived from the plasma/serum samples and DNA isolated from the antrum biopsies were analyzed by PCR amplification and pyrosequencing for the presence of interleukin-1beta gene (IL-1B) single nucleotide polymorphism (SNP). In addition, Southern blot and pyrosequencing analysis of H. pylori-specific PCR amplicons were performed. Results: IL-1B SNP profiles obtained from the plasma/serum MDA-DNA and antrum biopsy DNA were identical. A C/C genotype was observed in 7 of 9 samples, and 2 of 9 revealed a C/T genotype for IL-1B - 511. Similarly, 7 of 9 had a T/T, and 2 of 9 had a C/T genotype for IL-1B - 31, 4 of 9 had a C/C, 4 of 9 had a C/T, and 1 of 9 had a T/T genotype, respectively, for IL-1B + 3954. Moreover, pyrosequencing analysis revealed the presence of H. pylori 26695 and J99-like 16S rDNA variable V3 region sequence motifs in the antrum biopsies but not in the plasma/serum samples. Conclusions: We conclude that MDA combined with pyrosequencing enables a rapid and accurate molecular typing of cytokine single nucleotide polymorphisms from archival plasma/serum samples. © 2006 Elsevier B.V. All rights reserved.

  • 96.
    Szabó, Zoltán
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Rolf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Insulin resistance during coronary surgery in diabetic and non-diabetic patients-parallel microdialysis and organ balance technique studying skeletal muscle (preliminary results)2007In: Diabetologia(ISSN 0012-186X), vol 50, 2007, Vol. 50, p. 275-276Conference paper (Refereed)
  • 97.
    Szabó, Zoltán
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Rolf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Insulin resistance during coronary surgery in diabetic and non-diabetic patients-parallel microdialysis and organ balance technique studying skeletal muscle (preliminary results)2007In: European Association for the Study of Diabetes EASD,2007, 2007Conference paper (Refereed)
    Abstract [en]

        

  • 98.
    Szabó, Zoltán
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Intraoperative insulin resistance during coronary surgery in diabetic and non-diabetic patients- preliminary results2007In: EASD: Diabetes Cardiovascular Disease Study Group Meeting,2007, 2007Conference paper (Other academic)
  • 99.
    Särndahl, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Bergström, Ida
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Brodin Patcha, Veronika
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Nijm, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology.
    Setterud, Helen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Activation state of neutrophils in patients with stable coronary artery disease2007In: 76th Congress of the European Atherosclerosis Society,2007, 2007Conference paper (Other academic)
    Abstract [en]

       

  • 100. Söderlund, Gustav
    et al.
    Haarhaus, Mathias
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Chisalita, Ioana Simona
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Inhibition of puromycin-induced apoptosis in breast cancer cells by IGF-I occurs simultaneously with increased protein synthesis2004In: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317, Vol. 51, no 1Article in journal (Refereed)
    Abstract [en]

    The objective of the following work was to study the apoptosis inducing effect of puromycin in MCF-7 breast cancer cells and compare this effect with cycloheximide and emetine, 2 other inhibitors of protein synthesis. We also wished to investigate if the apoptosis modulating effect of insulin-like growth factor-1 (IGF-I) was similar for the 3 inhibitors. An immunological assay, quantifying mono- and oligonucleosome fragments and morphological criteria after nuclear staining, were used to study apoptosis. Protein synthesis was measured by incorporation of 3H-leucine in the cells, and solution hybridization and Western blot were performed to estimate IGF-I receptor m-RNA and IGF-I receptor protein respectively. Puromycin at 0.5 μg/ml induced a high level of apoptosis in MCF-7 breast cancer cells, although there was still a non-negligible amount of synthesized protein. In the case of cycloheximide and emetine, apoptosis occured when protein synthesis was almost completely blocked. IGF-I at a concentration of 10 ng/ml significantly reduced the level of apoptosis induced by puromycin, emetine, or cycloheximide. We also noticed a parallel increase in 3H-leucine incorporation when apoptosis induced by puromycin was lowered as an effect of IGF-I, in contrast to cycloheximide and emetine where IGF-I reduced the apoptosis level without increasing the 3H-leucine incorporation. At a higher concentration of puromycin (5. 7 μg/ml), which blocked protein synthesis, IGF-I at 10 ng/ml did not reduce apoptosis. The level of IGF-I receptor m-RNA was not influenced by the use of a concentration of puromycin (0.5 μg/ml) inducing a high degree of apoptosis. These results suggest, that reduction of puromycin-induced apoptosis by IGF-I occurs simultaneously with increased protein synthesis, in contrast to emetine and cycloheximide. Furthermore it would appear that puromycin-induced apoptosis is not caused by reduced levels of IGF-I receptors.

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