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J Hors

Publications and source records attributed to J Hors.

At least 73 records · Page 4Linked to original sources
PubMed1990

Marked shortage of C4B DNA polymorphism among insulin-dependent diabetic patients.

TaqI, BamHI and HinddIII polymorphisms of the C4 genes were studied with a 500-bp C4 cDNA probe (pAT-A153) specific for the 5' end of the gene. The restriction patterns obtained were correlated with the C4A and C4B genotypes in 35 patients suffering from insulin-dependent diabetes mellitus (IDDM), and results were compared to those from 40 healthy individuals. The controls, all Caucasian, were genotyped for HLA-A, B, C, DR, Bf, C2 and C4, together with 10 diabetics and their families; haplotypes for the other patients had been deduced using DNA and protein polymorphism, and taking into consideration linkage disequilibrium for neighbouring loci. No significant difference between genotypes at the C4A locus was seen in either population. The C4A gene deletion, associated with a C4B "short" gene (66.7%), was found mainly in the haplotype B8,Cw7,DR3,BfS,C2C, C4AQOB1, and the C4B gene deletion in the haplotype B18,Cw5,DR3,BfF1, C2C,C4A3BQO. When diabetic patients were compared with normal individuals, we observed, at the C4B locus, a decrease in the C4B "long" gene (22% vs. 49% respectively, p less than 0.001). A compensatory increase was observed in patients vs. controls for the frequency of C4BQO, both in the deleted and intact form (26% vs. 10% respectively, p less than 0.03).

Alleles↗
PubMed1990

A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus.

Family and population studies indicate that predisposition to insulin-dependent (type I) diabetes mellitus (IDDM) is polygenic. It has been shown that the absence of the aspartic acid in position 57 (Asp57) of the DQ beta chain is positively correlated to IDDM. However, Asp57-negative haplotypes do not always confer susceptibility and conversely, some Asp57-positive haplotypes seem to be disease associated. It has been suggested that other HLA class II sequences, probably belonging to the HLA DQA1 gene, confer susceptibility to IDDM. This report, based on extensive oligonucleotide dot blot hybridization of PCR-amplified DQA1 and DQB1 genes, reinforces the importance of the Asp57-negative DQ beta chain, but also introduces the possibility that a DQ alpha chain bearing an arginine in position 52 (Arg52) confers susceptibility to IDDM. A molecular model of susceptibility to IDDM is proposed. This model strongly suggests that the disease susceptibility correlates quantitatively with the expression at the cell surface of a heterodimer, composed of a DQ alpha-chain bearing an Arg52 and a DQ beta chain lacking an Asp57. In view of the respective positions of the two residues and their charge, we might anticipate that both residues DQ beta Asp57 and DQ alpha Arg52 are critical for modulation of susceptibility, presumably via viral-antigenic peptide and/or autoantigen presentation.

Base Sequence↗
PubMed1990

HLA DQ alpha/beta molecule associated with the susceptibility to insulin-dependent diabetes mellitus. A model for HLA/autoimmune disease association.

We have proposed a molecular model of susceptibility to Insulin-Dependent Diabetes Mellitus (IDDM) based on the proportional expression at the cell surface of the following susceptible (S-S) HLA-DQ heterodimere composed of a chain DQ alpha Arg 52 positive (S) and a chain HLA-DQ beta Asp 57 negative (S). All other DQ alpha/beta chains associations are considered as protective molecules. This model allows a predictive scale of risk for the disease.

Alleles↗
PubMed1990

[Genetic counseling of diabetics].

The information and counselling of diabetic patients and their families requires for the practitioner to know about some fundamental aspects of diabetes and in particular, to distinguish between the different types of diabetes with different causes, pathogenetic mechanism and modes of inheritance. Recent developments in the fields of immunogenetics have improved the understanding of type I diabetes, an auto-immune disease associated with HLA and made possible the identification of genetically susceptible individuals. The etiology of type II diabetes, by far the most frequent form, remains unknown. In the absence of genetical markers, the screening of predisposed subjects is, however, useful in order to propose preventive measures.

Diabetes Mellitus↗
PubMed1990

Typing for HLA DQ using oligonucleotidic probes.

We have typed 25 homozygous B lymphoblastoid cell lines, defined as reference panel during the Xth International Histocompatibility Workshop, using PCR (Polymerase Chain Reaction) and oligonucleotidic probes recognizing sequences of DQA and DQB genes. The polymorphism of 8 HLA-DQA1, and 12 DQB1 alleles is reported and the advantages of this technique are compared to that of other typing methods, currently used.

Cell Line↗
PubMed1990

[Epidemiology of juvenile insulin-dependent diabetes in Algeria (Wilaya of Oran)].

In order to precise the prevalence and incidence of IDDM in a well characterized population, we have ascertained between 1979 and 1988 all juvenile diabetic patients living in the department of Oran (Wilaya of Oran), Algeria, aged less than 20 years at the date of Dec. 31th 1988 who had onset of the disease before 15 years old. Cross comparisons of the data obtained both by a IDDM registry and a questionnaire sent to the practitioners show an excellent correlation. A total of 173 families was studied, including 155 Simplex Families (SF), and 18 Multiplex Families (MF). The prevalence was 0.27 p. 1000 among children aged less than 15 years. The annual incidence (mean = 4.4 p. 100,000) increased regularly from 1.6 p. 100,000 in 1981 to 8.1 p. 100,000 in 1988. The prevalence of IDDM among siblings was 3.8%. The birth order of index cases (first affected siblings) was lower in MF (3.0 +/- 0.4) than both in index cases of SF (4.0 +/- 0.3; p less than 0.01) and in secondary affected siblings of MF (4.8 +/- 0.05; p less than 0.001). The frequency of 2nd degree consanguineous marriages (between first cousins) was greater among the IDDM families compared with control families: 25% vs 11% (RR = 2.9; p less than 0.001).

Adolescent↗
PubMed1989

A retrospective and prospective study of the number of kidney transplants in 31 countries.

The aim of the present study was to try to predict the number of cadaveric kidney transplantations (CKT) that will be performed in the year 1993. The raw data regarding the number of renal transplants that have been performed annually since 1975 in 31 countries, which were divided into six groups, were collected from published reports and confirmed by a questionnaire sent to all centers. The annual number of grafts was estimated using an exponential model, highly correlated with retrospective data (r2 greater than 0.99). Predictions for 1993 were extrapolated. The growth of transplantation activity is limited by a shortage of available donor organs. The maximum number of grafts was arbitrarily set at 40 per million population, which is the maximum rate currently observed. The total number of CKT carried out between 1975 and 1986 was 114,000; this will probably exceed 280,000 in 1993. The yearly activity in 1987 exceeded 16,500 and is expected to reach approximatively 26,000 grafts in 1993.

Africa, Northern↗
PubMed1989

[Increased risk of insulin-dependent diabetes for siblings of diabetic children with the DR 3 haplotype of the mother].

Among 285 caucasoid families genotyped for HLA-A, B, C, DR including at least one insulin-dependent diabetic child, we have studied the effect of the DR3 and DR4 antigens inherited from the father or the mother (DR3p, DR3m, DR4p and DR4m, respectively) on the recurrence of the disease among siblings; families with affected parents being excluded, a total of 37 affected and 200 non affected siblings have been taken into consideration. Among the DR3, DR4 positive siblings, the DR4p/DR3m genotype was observed at a greater frequency than the DR3p/DR4m genotype among affected, but not among unaffected siblings. Comparing the respective frequencies between affected and unaffected siblings, the relative risk was 8.1 (p less than 10(-6) among DR4p/DR3m positive siblings, but is was not significantly increased among DR3p/DR4m positive siblings. The excess of maternal DR3 among affected siblings of diabetic children could be due to a gestational event associated with HLA-DR3, e.g. education of the fetal immune repertoire or the transmission of a viral infection by the mother to the fetus during pregnancy, after reactivation of the latent viral disease.

Diabetes Mellitus, Type 1↗
PubMed1988

[Value of the renal graft as a function of blood creatinine of the donors].

In a series of 851 renal transplantations, the fate of the grafted kidneys was studied in relation to the donors' renal function. The actuarial survival curves of the grafts showed no significant difference at 24 months between donors with blood creatinine levels below or above 150 mumol.l-1. Seventy-five of the 99 kidneys obtained from donors with high blood creatinine were functioning at 2 years. It would appear that the classical doubts about renal procurement from donors with high blood creatinine levels should be reconsidered.

Adolescent↗
PubMed1988

Factors associated with early remission of type I diabetes in children treated with cyclosporine.

To improve criteria for entry into future trials of immunosuppression, we enrolled 40 children with recent-onset Type I insulin-dependent diabetes in a pilot trial of cyclosporine. Twenty-seven patients were able to discontinue insulin therapy 48 +/- 5 days after the start of immunosuppression. At four months, their fasting and postprandial blood glucose concentrations averaged 110 and 160 mg per deciliter (6.1 and 8.9 mmol per liter) with a mean hemoglobin A1c level of 6.15 percent. Seventy-five percent of these patients with early remission still did not need insulin at 12 months, and their glycemic control was similar to that at 4 months. The major differences between the 27 patients with remission and the 13 without remission were the duration of symptoms before diagnosis (26.8 vs. 48.0 days, P less than 0.01), the degree of weight loss (3.2 vs. 10 percent of body weight, P less than 0.001), the initial hemoglobin A1c level (10.7 vs. 13.2 percent, P less than 0.001), and the frequency of ketoacidosis (11 vs. 61.5 percent, P less than 0.001). The lesser degree of weight loss was the strongest independent predictor of remission. The response of C-peptide to intravenous glucagon (0.50 vs. 0.17 pmol per milliliter, P less than 0.05) was also an independent predictor. No differences were observed between the two groups of patients in age, sex, HLA phenotype, autoantibodies to insulin or islet-cell antigens, or doses or trough levels of cyclosporine. Only minimal manifestations of toxicity were detected over the period of observation. We conclude that early treatment with cyclosporine in children with recent-onset Type I diabetes can induce remission from insulin dependence, with half the patients not requiring insulin after a full year.

Adolescent↗
PubMed1988

Two distinct HLA-DR3 haplotypes are associated with age related heterogeneity in type 1 (insulin-dependent) diabetes.

Heterogeneity between two haplotypes in linkage disequilibrium with DR3: B8, C4AQOB1,BfS,DR3 and B18,C4A3BQO,BfF1,DR3, with regard to age at onset of Type 1 (insulin-dependent) diabetes mellitus, was investigated in 325 unrelated French patients (146 males and 179 females, age at onset 1 month to 29 years) who were genotyped for HLA-A, B, C, DR and Bf and 225 of whom were typed for the C4A, B complement components. A subgroup of 82 patients and 75 control subjects were tested for DR beta and DQ beta DNA restriction fragment length polymorphism. The distribution according to age at onset and the mean ages at onset were compared between patients bearing B8, DR3 (n = 58), B18,DR3 (n = 62) or other DR3 haplotypes (Bx, DR3, n = 70), the haplotype segments C4AQOB1,DR3 (n = 41) or C4A3BQO,DR3 (n = 52) and the C4 null alleles C4AQO (N = 48) or C4BQO (n = 112) alone. The B8,DR3 haplotype, its smaller segment C4AQOB1,DR3 or C4AQO alone were associated with age at onset after 6 years (p less than 0.01, less than 0.08 and less than 0.02 respectively); on the other hand, the B18,DR3 haplotype, its segment C4A3BQO,DR3 or C4BQO alone were significantly more frequent in patients aged less than 6 years at onset (p less than 0.02, less than 0.01 and less than 0.01 respectively). Accordingly, the mean age of onset was significantly lower in the latter compared with the former patients (p less than 0.02, less than 0.02 and less than 0.01 respectively). No age-related variation was observed in BX,DR3 patients and their mean age of onset was intermediate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Organ-specific autoantibodies in HLA genotyped insulin-dependent diabetes mellitus families.

The prevalence of cytoplasmic islet cell antibodies (ICA) and extrapancreatic antibodies (EPA), (stomach, adrenal and thyroid) was investigated in 132 juvenile onset diabetic patients, without personal or familial history of other autoimmune disease, and their 31 diabetic and 402 non-diabetic first degree relatives. The prevalence of ICA was 59% in index cases and 12% in the non-affected first degree relatives. The frequency of EPA was 23% and 16% respectively. There were no sex-related differences among the patients. However, among the non-affected relatives, an increased frequency of EPA was observed in females (23%) compared to males (8%) (P less than 10-4). There was a higher prevalence of ICA in healthy relatives bearing DR3 and/or DR4 antigen combinations compared to non-DR3 and non-DR4 individuals (14% versus 5%, P less than 0.05). Furthermore, ICA were more frequent in healthy siblings sharing two haplotypes compared with one or no haplotype (21% vs 10%, P less than 0.05). These results support the heterogeneity of the autoantibodies: ICA are related closely to diabetes, decline in frequency with the duration of the disease and show association with DR3 or DR4 and the number of HLA haplotypes shared with the proband; EPA are sex related, independent of the duration of diabetes, non-HLA linked, and clustered in families with parent-offspring overtransmission, reflecting an overlapping autoimmune background.

Adolescent↗
PubMed1988

HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes.

Since HLA-DRw15 (a subdivision of the HLA-DR2 specificity previously called DR2 long) is associated with dominant nonsusceptibility to insulin-dependent diabetes mellitus (IDDM), while HLA-DRw16 (another subdivision of HLA-DR2, previously called DR2 short) is positively associated with the disease, we looked for particular characteristics of HLA products encoded by the DR2 haplotypes of IDDM patients. The results show the following: (i) HLA-DQ molecules of HLA-DRw15-positive IDDM patients are different from those of HLA-DRw15-positive controls, suggesting that the HLA-DQ gene of DRw15 haplotypes is involved in a protective effect. (ii) HLA-DR and -DQ products of DRw16-positive IDDM are functionally indistinguishable from those of HLA-DRw16-positive controls. Furthermore, our data provide evidence that the residue at position 57 on the DQ beta chain could play a crucial biological role in antigen presentation to T cells as far as the DRw16 haplotype is concerned. This observation fits with the recent observation of correlation between DQ beta allelic polymorphism at position 57 and both susceptibility and resistance to IDDM.

Amino Acid Sequence↗
PubMed1988

Study of HLA antigens in a population of Mali (West Africa).

Eighty-two healthy individuals have been typed for HLA-A, B, C, antigens, and 49 of them also for HLA DR alleles. They were a sample representative of 11 of the 14 Malian ethnic groups living in the area of Bamako (Mali). Phenotypic frequencies have been compared to those of other Negroid and Caucasoid reference populations. As expected, in Negroids the increased frequency of HLA A23, A28, A30, and ATh was confirmed in the present series. Additionally, a significantly increased frequency of HLA B5 (B51 and Bw52) was noted--already observed in some but not all Negroid populations. Conversely, a decreased frequency--compared with that usually found in Negroid population--was observed for the alleles Bw42, Bw58, Cw6, and DRw6. Our results underline the originality of the Malian population among Western Africans.

Black People↗
PubMed1988

MHC classes I, II, III antigens study in 70 insulin-dependent diabetics with associated auto-immune diseases.

Seventy IDDM patients (insulin-dependent diabetics), 48 females and 22 males, most of them adults at the onset of diabetes, and suffering from at least one other associated autoimmune manifestation (AAM) were studied for HLA A,B,C, DR markers and Bf, C4 complement components. Comparisons were made with 108 normal controls and a series of 287 IDDM patients with juvenile onset (under 25 years) and no patent other autoimmune disease. The increase in frequency of HLA-B8 among IDDM patients with AAM was confirmed (36% versus 20% in controls) (p less than 0.04). The frequency of DR4 among diabetics with AAM (33%) was not significantly different from the normal frequency (27%), and the allelic combination DR3/4 was found in only 13% of IDDM with AAM. Corresponding frequencies in patients with IDDM alone were 66% for DR4 and 34% for DR3/4 (p less than 10(-6) and 10(-3) respectively). These results confirm the heterogeneity of IDDM and support, by genetic arguments, the concept of overlapping entities. The hypothesis of a common background of autoimmunity associated with B8 DR3 can be postulated, while the organ specific target process should be associated with various DR alleles.

Adolescent↗
PubMed1988

Study of cis and trans interactions between extended HLA-haplotypes in insulin-dependent diabetes.

From the study of HLA, A, B, C, DR, Bf and C4A, C4B alleles in 287 insulin-dependent diabetes mellitus patients and 108 controls, comparisons were made between 424 diabetic and 216 normal extended haplotypes. In the "cis" situation (haplotype), the highest relative risks (RR) for IDDM were borne by multiloci allelic associations, mainly DR/complement alleles, rather than by DR3 or DR4 considered alone. Susceptibility was strongly associated with two extended haplotypes (Aw30, Cw5, B18, C4BQ0, C4A3, BfF1, DR3 and A2, Cw3, B15, C4Bx, C4A3, BfS, DR4) or their smaller segments. Two haplotypes, S31 associated with DR2 or DR5 and F31 associated with DRw6 or DR7 had a protective effect. In the "trans" situation (opposite haplotype) the large excess of DR3/DR4 heterozygotes was not the only distortion observed. An excess of DR1 (57%) and of C4BQ0 (40%) was noted among non DR3, non DR4 haplotypes in diabetics compared to normal individuals (26% and 23%, respectively, P less than 0.01, 0.05). Homozygotes for DR3 or DR4 were not increased, and other homozygotes were decreased compared to controls. The protective antigens HLA DR2, DR5 and DR7 seemed not to be distributed randomly: their putative protective effect was not observed in the case of combination with DR1 or a B18, DR3 haplotype. DR2 was never found homozygous or combined with DR5. These results suggest that susceptibility to IDDM is generated by both cis and trans interactions between genes or gene products of the HLA region.

Alleles↗