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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of oral pathology & medicine 15 (1986), S. 0 
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have examined the keratin proteins in normal human oral mucosa from 6 different regions including hard palate, buccal mucosa, tongue, gingiva and floor of the mouth. Urea-dithiothreitol extracts of EDTA separated epithelia were analysed by SDS-PAGE and immunoblotting. Eight samples from each region were investigated and showed very little individual variation in the keratin profile on Coomasic Blue-stained gels. The keratinizing hard palate and gingiva expressed identical patterns and resembled the pattern of epidermis from the flank region. The normally non-keratinizing buccal mucosa and the mucosa of the floor of the mouth expressed polypeptides distinctly different from those of the keratinizing epithelia and lacked the high molecular weight keratins. The dorsal surface of the tongue and the commissure region showed a pattern intermediate between keratinizing and non-keratinizing epithelia. The greater sensitivity of the immunoblotting technique revealed that the non-keratinizing epithelia synthesized one of the high molecular polypeptides and that the tongue produced all the bands found in keratinizing epithelia, but in very small quantities. There are, thus, distinct differences in the keratin expression of oral epithelia which are related to the pattern of keratinization assessed histologically.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: T lymphocyte subpopulations ; Type 1 diabetes ; monoclonal antibodies ; helper/inducer T cells ; suppressor/cytotoxic T cells ; fluorescence-activated cell sorter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary T lymphocyte subsets in peripheral blood from 11 newly diagnosed Type 1 (insulin-dependent) diabetic patients were studied prospectively at three time intervals: as soon as possible after diagnosis, 3 weeks and 5 months later. Lymphocytes were marked with monoclonal OKT antibodies and examined in a fluorescence-activated cell sorter. The percentage of T lymphocytes (OKT 3) did not change significantly at the three study times. The percentage of helper/inducer T cells (OKT 4) was high the first week after diagnosis, but decreased at the 5-month examination (p〈0.05). The percentage of suppressor/cytotoxic T cells (OKT 8) was low at diagnosis but increased at 3 weeks (p〈0.02) and 5 months (p〈0.01). The ratio OKT4/OKT8 lymphocytes was 2.28 at diagnosis, decreasing to 1.77 at 3 weeks and 1.87 at 5 months, compared with 1.46 for 16 age-matched control subjects. There was no significant change in the absolute number of lymphocytes. It is concluded that the distribution of T cell subsets was abnormal at the time of diagnosis, but changed towards normal within a few weeks, after which there was no significant change at 5 months. It is as yet unknown whether the high proportion of helper/inducer T cells and/or the low percentage of suppressor/cytotoxic T cells at diagnosis favour immune reactions involved in the pathogenesis of Type 1 diabetes.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords Glucose stimulation ; beta-cell line ; MIN6 ; transcription factor ; Egr-1.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A copy deoxyribonucleic acid (cDNA) clone of the immediate early growth response gene, egr-1 (Krox-24, Zif268, NGFI-1), was isolated through subtractive hybridization screening to identify glucose-induced genes in pancreatic beta cells. Glucose rapidly and transiently induced egr-1 mRNA in the SV40-transformed murine beta-cell line, MIN6. Glucose also increased egr-1 mRNA expression in INS-1, βTC3 and RINm5F beta-cell lines, although with different kinetics. Expression of the 82 kDa Egr-1 protein was induced both in MIN6 cells stimulated with glucose in vitro and in primary rat islet cells stimulated in vivo or in vitro. This response is unique to beta cells since glucose did not affect egr-1 expression in NIH-3T3 fibroblasts or glucose-sensitive hepatocytes. In beta cells egr-1 induction is specifically associated with insulin secretion, as it was not observed after stimulation with serum or insulin but was elicited by insulin secretagogues, including membrane depolarizing agents and cAMP agonists. Moreover, induction of egr-1 by glucose was inhibited by EDTA, indicating dependence on influx of extracellular Ca2+. Other immediate early response genes, c-fos and junB, were also induced following glucose stimulation with kinetics similar to egr-1, whereas c-jun and junD expression were not affected. Since the zinc-finger protein encoded by egr-1 is highly homologous to transcription factors that control expression of glucose-regulated genes in yeast, Egr-1 could mediate delayed adaptive responses of beta cells to sustained glucose stimulation through transcriptional regulation. [Diabetologia (1999) 42: 195–203]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Incidence ; seasonal variation ; geographical pattern ; sex-difference ; epidemiology ; juvenile-onset ; insulin-dependent ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The incidence, sex, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus (j.i.d.m.) were studied retrospectively on one third of the Danish population 1970–1974. The j.i.d.m. incidence remained fairly constant during the study period, the average being 13.2 per 100000 per year. The total number of boys exceeded the number of girls by 27 per cent. A marked peak of incidence was found at 12–14 years, earlier for females than for males. A seasonal variation in onset (diagnosis) of j.i.d.m. was observed with the lowest number of new cases in May–July. The j.i.d.m. incidence seemed to show socioeconomic differences, being highest in those parts of the survey area with lower status.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords GAD65 ; IAA ; ICA ; HLA ; gestational diabetes ; pregnancy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the presence of GAD65 autoantibodies in women with insulin-dependent diabetes mellitus (IDDM) (n = 28) or gestational diabetes (GDM) (n = 139) diagnosed during pregnancy and investigated the temporal relationship between these autoantibodies and the subsequent recurrence or development of IDDM. Among the GDM patients, 4.3 % (6 of 139) developed true IDDM during a median follow-up period of 6.3 years (range 4.0–11.0). Of these, 2.2 % (3 of 139) were positive for GAD65 autoantibodies at diagnosis of GDM compared to 0 % (0 of 27) of healthy pregnant women. All 3 GAD65 autoantibody positive GDM patients subsequently developed IDDM after a median of 14 months (range 4–34). GAD65 autoantibodies were present in 50 % (14 of 28) of sera from women with IDDM diagnosed during pregnancy. The non-insulin-requiring remission period was significantly shorter in GAD65 autoantibody positive patients (median 0.5 years [range 0–6.0 years]) than in GAD65 antibody negative patients (median 2.6 years; range 0–9.7 years; p 〈 0.05). The results suggest that screening for GAD65 autoantibodies in women with GDM or IDDM diagnosed during pregnancy may be useful for predicting the clinical course of the disease. [Diabetologia (1996) 39: 1329–1333]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; pregnancy ; prognostic parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The study concerns the clinical outcome and later prognosis (regarding permanent insulin treatment) of patients who develop insulin-dependent diabetes mellitus during pregnancy (which is different from gestational diabetes). Sixty-three such patients (27±1 (SEM) years old) were delivered at the Copenhagen Centre for Diabetes and Pregnancy during the years 1966–1980. Obstetric complications such as toxaemia were seen in 9.5% of these study patients and the perinatal mortality was 6.3%, both percentages being higher than in the general population (1.1%,p〈10−7 and 1.0%,p〈10−3, respectively), but similar to those observed in patients with Type 1 diabetes diagnosed before pregnancy. In contrast, the frequency of malformations was 1.6%, the same as in the general population (1.4%), but lowerthan that seen in patients with long-standing diabetes (8.3%,p〈0.05). At follow-up examination 8±1 years after diagnosis all patients were diabetic; 77% were insulin treated, having no or virtually no residual B-cell function, and were clearly Type 1 diabetic patients. After delivery 80% of the patients had a remission period (median 256 days) without insulin treatment. This remission period was absent or shortest in patients with the following characteristics (p≤0.03): low age, first parity, not overweight, and high blood glucose level at diagnosis. These prognostic parameters should be considered in obligatory, clinical follow-up plans for such patients.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Keywords Endothelin-1 ; insulin secretion ; glucagon secretion ; flow cytometry ; alpha cell ; beta cell ; clonal cell line ; endothelin receptor ; gene expression.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The circulating concentrations of endothelin-1 (ET-1), a peptide derived from endothelium, are increased in hypertension and diabetes. Endothelin-1 has recently been shown to be an insulinotropic agent. The mechanism of action of endothelin-1 on the endocrine pancreas has not yet been clarified. Methods. We investigated the action of endothelin-1 on the insulin secretion, the binding of 125I-ET-1 to beta cells as well as its effects on purified beta and non-beta cells from normal rats. The expression of endothelin receptors in alpha- and beta-cell lines and in normal rat islets was also studied. Results. First, we studied the effects of endothelin-1 on insulin secretion from beta-cell lines (INS-1, βTC3 and MIN6). At all endothelin-1 concentrations applied (1 pmol/l to 1 μmol/l) no change in insulin secretion was found. Ligand-binding experiments on βTC3 cells showed no specific binding of 125I-ET-1. A prominent expression of ETA-receptor mRNA in an alpha-cell line (αTC1.9) and in normal rat islets was found whereas no expression was found in INS-1 cells. No influence of endothelin-1(1 μmol/l) on insulin secretion stimulated by glucose was detected from purified beta cells. Endothelin-1-(100 nmol/l) increased, however, both insulin and glucagon secretion from a mixture of purified beta and non-beta cells indicating that alpha cells seem to have a key role for the action of ET-1 on insulin secretion. Conclusion/interpretation. The insulinotropic impact of endothelin-1 is not caused by a direct action on the beta cells but seems to be mediated by a paracrine action, probably secondary to enhanced release of glucagon from the endothelin receptor positive alpha cells. [Diabetologia (1999) 42: 1302–1307]
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 24 (1983), S. 42-46 
    ISSN: 1432-0428
    Keywords: Encephalomyocarditis virus ; diabetes mellitus ; athymic nude mice ; the thymus-dependent immune system ; cyclophosphamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study concerns the effect of the experimental diabetogenic encephalomyocarditis (EMC) virus on normal and athymic nude mice of BALB/c origin. The effect of simultaneous immunosuppressive pharmacological treatment with a derivative of cyclophosphamide in a relatively low dose (3 mg/mouse) was also studied. After inoculation with EMC virus, 36% of the normal mice, but none of the nude mice, developed diabetes mellitus and 93% of the normal mice, but none of the nude mice, developed paresis of one or more leg(s). When lower doses of EMC virus were given, few or none of the normal mice developed diabetes or paresis. After treatment with a cyclophosphamide-derivative, the number of paralysed mice increased. EMC virus in abundant amounts could be isolated from the pancreas and heart of all virus-inoculated mice, including the non-diabetic nude mice. Antibodies against EMC virus were found in all groups of virus-inoculated mice, although only in small amounts in nude and immunosuppressed normal mice. Histological examination revealed no significant differences between the islets of Langerhans of the experimental mice, diabetic as well as non-diabetic, and the control mice with respect to lymphocytic infiltration. It is concluded that the thymus-dependent immune system seems to be of decisive importance for the development of diabetes in this virus model.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; glycolipids ; sulphatide ; islets of Langerhans ; kidney ; peripheral nerves ; eye ; ovary ; thin-layer chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sulphatide has been found in rat islets of Langerhans and anti-sulphatide antibodies have been demonstrated in patients with insulin-dependent diabetes mellitus. Using a specific monoclonal antibody, Sulph I, directed against sulphatide, we investigated the in situ distribution of this glycolipid immunohistochemically; furthermore, the sulphatide concentration was determined in several organs and cells by thin-layer chromatography. The islets of Langerhans in all species examined, mouse, rat, pig, and monkey were intensively stained but exocrine tissue remained unlabelled. The sulphatide concentration in human islets was 150±46 pmol/100 islets. The only glycolipid-antigen detected was sulphatide. Regarding other tissues, sulphatide was found to be located in distal tubules in the kidney, peripheral nerves, distinct scattered spot-like structures in the choreoid layer of the eye, the ovum, and peripheral granulocytes. Sulph I injection in mice showed homing to kidney tubules. Lung, heart, liver, adrenal, spleen, lymph node and thymus were not stained by Sulph I. Thus, the distribution of sulphatide shows an association with organs known to be affected in diabetes, either initially or in late complications.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Key words Diabetes mellitus ; glycolipids ; sulphatide ; islets of Langerhans ; kidney ; peripheral nerves ; eye ; ovary ; thin-layer chromatography.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sulphatide has been found in rat islets of Langerhans and anti-sulphatide antibodies have been demonstrated in patients with insulin-dependent diabetes mellitus. Using a specific monoclonal antibody, Sulph I, directed against sulphatide, we investigated the in situ distribution of this glycolipid immunohistochemically; furthermore, the sulphatide concentration was determined in several organs and cells by thin-layer chromatography. The islets of Langerhans in all species examined, mouse, rat, pig, and monkey were intensively stained but exocrine tissue remained unlabelled. The sulphatide concentration in human islets was 150 ± 46 pmol/100 islets. The only glycolipid-antigen detected was sulphatide. Regarding other tissues, sulphatide was found to be located in distal tubules in the kidney, peripheral nerves, distinct scattered spot-like structures in the choreoid layer of the eye, the ovum, and peripheral granulocytes. Sulph I injection in mice showed homing to kidney tubules. Lung, heart, liver, adrenal, spleen, lymph node and thymus were not stained by Sulph I. Thus, the distribution of sulphatide shows an association with organs known to be affected in diabetes, either initially or in late complications. [Diabetologia (1994) 37: 1000–1006]
    Type of Medium: Electronic Resource
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