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J Barbosa

Publications and source records attributed to J Barbosa.

At least 127 records · Page 7Linked to original sources
PubMed1984

Genetic heterogeneity of insulin-dependent (type I) diabetes mellitus: evidence from a study of extended haplotypes.

Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf-DR alleles on a chromosome) were also contrasted with control frequencies. Significant positive associations between IDDM and HLA-B8, DR3, DR4, BfS, and BfF1 were confirmed, as were significant negative associations between IDDM and HLA-B7, DR2, DR5, DR7, and BfF. One haplotype (B7-BfS-DR2) exhibited significant negative association, while five haplotypes (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4) exhibited significant positive associations with IDDM. In this sample, 64% of all probands carried at least one of the high-risk haplotypes. In conclusion, the occurrence of five "high-risk" haplotypes associated with IDDM provides evidence for previously undocumented genetic heterogeneity and suggests that possibly more than two HLA-region genes may be involved in IDDM susceptibility.

Adolescent↗
PubMed1983

Isolated tricuspid stenosis: report of a case submitted to valvular commissurotomy.

In this report, a rare case of tricuspid stenosis uncomplicated by other valve lesions is presented, with clinical, hemodynamic, echocardiographic, and angiographic studies. The patient was markedly incapacitated, mostly as a result of a restricted cardiac output. Tricuspid commissurotomy was performed, with a stenotic deformity of a bicuspid atrioventricular valve, probably of congenital origin, found at surgery. Considerable improvement was observed, notwithstanding the persistence of some signs of residual tricuspid obstruction as a result of an incomplete commissurotomy, to avoid increasing the slight degree of preexistent valvular regurgitation.

Cardiac Catheterization↗
PubMed1983

The development of lesions in the glomerular basement membrane and mesangium after transplantation of normal kidneys to diabetic patients.

Renal allograft biopsies at the time of transplantation (baseline) and 2 yr later were obtained in 6 type I diabetic and 12 nondiabetic patients and studied for glomerular basement membrane (GBM) and mesangial changes. Diabetic patients had significantly greater GBM thickness compared with nondiabetics at 2 yr (P = 0.05, rank sum test), and the increase in GBM thickness comparing baseline and 2-yr biopsies was greater in the diabetic compared with nondiabetic patients (P = 0.005, rank sum test). Similarly, diabetic patients developed significant mesangial thickening by light microscopy while no changes were observed in nondiabetic patients (P = 0.001). Electron microscopic morphometric analysis of the percentage of total mesangium was not different on comparing diabetic and nondiabetic patients at 2 yr. There was an increase in the matrix component of the mesangium in the diabetics at this time, although this did not reach statistical significance (P = 0.06). In addition, the surface density of the peripheral glomerular capillary wall, presumably reflecting mesangial expansion, was decreased in the diabetic and unchanged in the nondiabetic patients (P = 0.005). These studies document, for the first time, the development of GBM and mesangial lesions of diabetic nephropathy in normal living related donor and cadaver kidneys transplanted into diabetic patients and support the hypothesis that these lesions are secondary to the diabetic state.

Adult↗
PubMed1983

Heterozygous expression of insulin-dependent diabetes mellitus (IDDM) determinants in the HLA system.

HLA phenotypes of cases with insulin-dependent diabetes mellitus (IDDM) and identity by descent of HLA haplotypes in affected sib-pairs support an intermediate model in which morbid risk is increased by one HLA-linked IDDM determinant, and greatly increased by two determinants, which may be qualitatively different in DR3 and DR4 haplotypes. Linkage analysis allowing for gametic disequilibrium reveals no recombination in pedigrees with a DR3/DR4 propositus, but spurious recombination in the remaining pedigrees. This evidence favors interaction of unlinked IDDM determinants to produce affection in a small proportion of heterozygotes for an HLA-linked determinant. Partition of data by HLA type of the propositus (ideally by DR and the complement types jointly) is a powerful method to resolve etiological heterogeneity for HLA-associated diseases.

Adult↗
PubMed1983

Quantitative glomerular morphology of the normal human kidney.

We determined glomerular basement membrane (GBM) width (as the harmonic mean) and relative volumes of the glomerular mesangium and of its cellular and matrix components in 59 male (73% living-related) and 59 female (93% living-related) donors of kidneys for transplantation. The GBM, consistently wider in male (mean, 373 nm.) versus female (mean, 326 nm.) donors, increased in width in all donors until the fourth decade of life when it appeared to decrease in width. The relative volume of the mesangium did not differ as to sex or age (mean, 14.2% of the glomerular volume), nor did either of its components (mean cellular mesangium, 7.1%; mean matrix mesangium, 7.1%). We found no correlations among renal index, GBM width, or the mesangium. No parameter differed in diabetic-related compared with nondiabetic-related donors. Results in cadavers for GBM width and the mesangium were no different from those of living-related donors. These observations yield insights into the development of the human kidney and its glomerular components, and in addition the GBM and mesangial measures will serve as normative values to which surgical or biopsy specimens can be related.

Adolescent↗
PubMed1982

Heterogeneity of insulin-dependent diabetes-new evidence.

We have performed complex segregation and linkage analysis in 182 families with at least one insulin-dependent diabetic proband. All families were typed for B histocompatibility (HLA) antigens and 118 for DR. The recessive model fit the data best, with maximum likelihood estimates of recombination between HLA DR and the susceptibility factor of 0.019. Substantial heterogeneity was suggested, with smallest estimated recombination for pedigrees whose probands have two high-risk DR alleles. The results are compatible with a strong, tightly HLA-linked susceptibility factor and evidence for additional non-HLA linked genetic factor(s).

Diabetes Mellitus, Type 1↗
PubMed1982

Genetic heterogeneity of diabetes and HLA.

Histocompatibility (HLA) antigens and genotypes B, D and DR were studied in large sample of Caucasian insulin dependent diabetic (IDD) probands. The associations between IDD and B8, B15, Dw3, Dw4, and DR3, and DR4 were measured by relative risks (RR) and delta values. Both the homozygotes (B8/8: RR 10, B 15/15: RR 7, DR3/3: RR32, DR4/4: RR34) and the heterozygotes (B8/15: RR 11, DR3/4: RR22) for the high-risk antigens showed highly significant elevation of the relative risks, yet there were no statistically significant differences between the homo- and the heterozygotes. The delta measurements supported the RR results. RR and delta were found significantly decreased for B7, Dw2, and DR2. There were no relationships observed between age at diagnosis or family history and HLA. Although we were unable to demonstrate a statistically significant difference between the RR for the high-risk antigens heterozygote vs. the high-risk antigen homozygotes, our study like many others shows that the RR is higher for the heterozygotes. Thus our data are compatible with genetic heterogeneity of IDD.

Adolescent↗
PubMed1982

HLA and susceptibility to type I diabetes. Hypothesis.

Positive associations between the antigens D(R)3 and D(R)4 and negative associations of D(R)2 have been reported with insulin dependent or type I diabetes mellitus. It has been suggested that susceptibility factor(s) associated with the D(R)3 and D(R)4 haplotypes and a resistance factor associated with the D(R)2 haplotype may be involved in the pathogenesis of the disease. We propose a hypothesis herein which attempts to unify these findings based on our present understanding suggesting (a) the existence of multiple antigenic determinants associated with any one D(R) haplotype and (b) the sharing of "single" D region encoded determinants between what we now refer to as different D(R) haplotypes. The hypothesis, in its simplest form, focuses on a single D region determinant which can be found associated at different frequencies with the various D haplotypes as potentially explaining the findings.

Diabetes Mellitus↗
PubMed1982

Linkage disequilibrium between insulin-dependent diabetes and the Kidd blood group Jkb allele.

We studied 102 randomly ascertained probands from the Upper Midwest United States with insulin-dependent diabetes mellitus (IDDM) with respect to both HLA-DR and Kidd (Jk) markers. Based on our evidence that multiple genetic mechanisms may be involved in the etiology of IDDM the data were partitioned according to the HLA-DR phenotype, containing either two high risk antigens (DR3 or DR4) or not. Probands with two such antigens showed no applicable deviation from control frequencies, while the remainder displayed a slightly reduced relative risk for Jka (RR = 0.70, p less than .25), but a significantly elevated risk for Jkb (RR = 2.53, p less than .025). These results strongly suggest a complex model of IDDM inheritance involving, at least, one susceptibility locus in linkage disequilibrium with HLA DR3 and DR4 on chromosome 6, and a second locus in linkage disequilibrium with Jkb on chromosome 2.

Adolescent↗
PubMed1982

No evidence for linkage between diabetes and the Kidd marker.

We have studied linkage analysis between the Kidd (Jk) red blood cell marker locus and insulin-dependent diabetes mellitus (IDD) in an attempt to confirm the preliminary report of Hodge et al. One hundred thirty-two families with one IDD proband (67 simplex and 65 multiplex families) were analyzed using the LIPED computer program and assuming three genetic models (autosomal recessive, additive, and dominant) with parameters similar to those used by Hodge et al. The lod scores at zero recombination were - 18.51, - 11.62, and - 6.03 for the recessive, additive, and dominant models, respectively. These results constitute significant evidence against tight linkage between Kidd and IDD, while providing no evidence for looser linkage, and are in contrast with the positive lod scores found by Hodge et al. in a different population.

Blood Group Antigens↗
PubMed1982

Empirical risk for insulin-dependent diabetes (IDD) in sibs. Further definition of genetic heterogeneity.

We have studied the effect of age at diagnosis in the proband and parental status [normal versus non-insulin-dependent diabetes (NIDD)] on the cumulative risk to age 40 (CR40) for insulin-dependent diabetes (IDD) in sibs of IDD probands in 493 families. We found a significantly increased cumulative risk to age 40 fro IDD in sibs of probands with disease diagnosed before age 10 (8.5 +/- 2.0%) as compared with that in sibs of probands with disease diagnosed after age 10 (4.6 +/- 0.8%) (X2 = 7.6, P = 0.006). Within the family subset with probands of earlier IDD onset (before age 10) we also found an increased CR40 for IDD in the sibs of the probands in families with an NIDD parent (with NIDD parent: CR40 = 7..5 +/- 2.0%, X2 = 12.8, P less than 0.0005). These data are compatible with the theory of heterogeneity (genetic and/or environmental) of IDD and a possible relationship between IDD and NIDD.

Adolescent↗