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  • 1
    ISSN: 1432-0428
    Keywords: Acute insulin response ; Type 1 (insulin-dependent) diabetes mellitus ; risk ; glucose ; glucagon ; arginine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationships between first-phase insulin secretion to i.v. glucagon and i.v. arginine were studied in 19 healthy adult volunteers (Group I) and in 21 subjects at risk for Type 1 (insulin-dependent) diabetes mellitus with either a “normal” (n=11; Group II a) or a “low” insulin response to i.v. glucose (n=10; Group II b). Groups I and II a displayed similar insulin responses to the three secretagogues. In contrast, Group II b demonstrated lower insulin responses to both glucagon and arginine than control subjects (p}〈0.007 and (p}〈0.04 respectively) orthan “normo-responders” to glucose (#x007D;〈0.007 and p〈0.04 respectively). In Group II b however, arginine-stimulated insulin release was increased compared to the response to glucose (p}〈0.006), while glucagon and glucose led to non-statistically different responses. Five “low-responders” developed Type 1 diabetes. As a group, they displayed lower responses to glucagon and to arginine than subjects who up to now have not developed the disease (p〈0.05 and p〈0.0003 respectively). In the subjects who progressed to diabetes, the responses to glucose and glucagon were similarly blunted. In the “low-responders” who have not developed the disease, no statistical difference could be detected between mean responses to glucagon and glucose, but four out of these five subjects had a glucagon-stimulated response within the control range and higher than their corresponding response to glucose. Arginine led to a higher stimulation than glucose, in subgroups that either progressed to diabetes (p〈0.006) or did not (p〈0.002). Finally, “low-responders” who did not develop diabetes displayed similar responses to both glucagon and arginine than “normo-responders” to glucose. A progressive decrease of arginine-stimulated insulin response may be a later event during pre-Type 1 diabetes than a blunted response to glucose, while a loss of glucagon-stimulated insulin release may be intermediate. Diminished response to all secretagogues may offer better prediction than a “low” response to glucose alone.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 23 (1996), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The non-classical HLA-G gene is the only class I antigen expressed in trophoblasts at the maternofetal interface. In placenta, the HLA-G gene produces several alternatively spliced isoforms encoding bound-membrane proteins (G1, G2, G3 and G4) lacking, respectively, exon 7; exons 7 and 3; exons 7, 3 and 4, and exons 7 and 4. In addition, two isoforms (G1s and G2s) containing an intron 4 sequence are able to encode soluble antigens. We have recently reported that the HLA-G gene is transcriptionally active in lymphocytes and is not transcribed in CD34+ cells, polynuclear cells or monocytes. To investigate the functional significance of the different isoforms in lymphocytes, we studied their distribution in normal T and B lymphocytes and in malignant lymphoid cells by using the RT-PCR technique followed by hybridization with exon-specific probes and sequencing assays. In transcriptionally active lymphocytes, the HLA-G primary transcript is the major form and is differentially spliced in B and T lymphocytes: (i) G1s is found in several samples of T and B cells whereas G2s is only transcribed in T lymphocytes, (ii) the G4 isoform is never detected in B lymphocytes. In addition, we have shown that HLA-G is inactive in some samples of lymphocytes. Our data suggest that HLA-G transcription is regulated at the initiation level and at the subsequent splicing. These two levels of regulation may be dysregulated in some cases of T-ALL and CLL. The potential functions of the HLA-G alternative forms in lymphocytes, such as peptide binding and modulation of the immune response, are discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The aim of this study was to determine immunogenetic markers of susceptibility in Crohn's disease (CD), taking the different features of the clinical course of the disease into account. HLA class I, HLA class II and TAP transporter gene polymorphisms were studied using DNA typing methods. Gene and antigen frequencies were analysed and compared in a group of 102 CD patients and 200 unrelated healthy controls from the same area. Analysis of the whole CD patient population revealed no definite association with either HLA or TAP gene alleles, with the exception of an association with DRB1*1302 (Pc 〈 0.05). However, when clinical subgroups of patients were considered, specific associations with some genetic markers were found. The most definitive results involved a genetic association in the group of patients who did not respond to glucocorticoid therapy. This group was characterized by a high frequency of HLA-DRB1*04 (P 〈 0.05). Conversely, a positive association with the TAP2-A allele was found in cortico-responder patients (Pc 〈 0.03). Furthermore, analysis of the distribution of HLA class II alleles in relation to the presence of extra-intestinal manifestations revealed an association with the DQB 1*0501 or *0503 suballele of DQ5 (P 〈 0.05). Finally, patients with lesions in the small bowel were more frequently HLA DRB1 *07 (P 〈 0.05). The present study supports the concept of clinical heterogeneity in Crohn's disease associated with a background of genetic heterogeneity.
    Type of Medium: Electronic Resource
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