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Biomedical subjects

J Barbosa

Publications and source records attributed to J Barbosa.

At least 109 records · Page 6Linked to original sources

Association of viral hepatitis A with HLA-A9.

HLA-A and B phenotyping was carried out, during a viral hepatitis A (VHA) epidemic in Brazil, on 47 unrelated patients with VHA and 53 unrelated healthy subjects of the same age, sex, social status, and ethnic origin. An increased frequency of HLA-A9 (44.7% vs. 15.1%) and a decrease of that of HLA-A3 (2.1% vs. 22.6%) were observed when compared with controls. After correction for the number of antigens tested, only the positive association with HLA-A9 was observed. It was found that the relative risk for an HLA-A9 carrier to develop VHA was 4.5.

Adolescent↗

Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth.

Complementary DNA (cDNA) clones encoding the heavy chain of the heterodimeric human membrane glycoprotein 4F2 have been isolated by immunoscreening of a lambda gt11 expression library. The identity of these clones has been confirmed by hybridization to RNA and DNA prepared from mouse L-cell transfectants, which were produced by whole cell gene transfer and selected for cell-surface expression of the human 4F2 heavy chain. DNA sequence analysis suggests that the 4F2 heavy-chain cDNAs encode an approximately 526-amino acid type II membrane glycoprotein, which is composed of a large C-terminal extracellular domain, a single potential transmembrane region, and a 50-81 amino acid N-terminal intracytoplasmic domain. Southern blotting experiments have shown that the 4F2 heavy-chain cDNAs are derived from a single-copy gene that has been highly conserved during mammalian evolution.

Amino Acid Sequence↗

Buffy coat transfusions in early type I diabetes.

Fresh whole-blood buffy coats from American Red Cross volunteers were used to treat early type I diabetes. Attempts were made to adapt to human diabetic patients a protocol successfully used in prediabetic BB rats. Twenty-two type I diabetic patients (duration of disease less than 4 wk) were randomized to treatment or control groups; the treatment patients were given one buffy coat (approximately 0.6 X 10(9) T-lymphocytes) weekly for 5 wk. Plasma C-peptide (stimulated and unstimulated), insulin dose, and hemoglobin A1c were measured before and periodically after the treatment for 24 wk. The control group underwent the same studies. Although there were no significant differences for the parameters studied between the two groups, 2 of 12 patients in the treatment group underwent three complete (normal glycemia without insulin) temporary remissions. One of these patients was given a second course of transfusions after relapse from the first remission and developed a second complete remission that lasted 2 mo. No control patient had remissions during the 24-wk study. Although the future of adoptive immunotherapy in the treatment or prevention of diabetes is not known, several probable limitations of the current protocol, as discussed here, can explain the differences in results between this trial and the rodent studies.

Adolescent↗

A combined segregation and linkage analysis of insulin-dependent diabetes mellitus.

In an effort to clarify the mode of inheritance of insulin-dependent diabetes mellitus (IDDM), a total of 230 nuclear families with pointers were analyzed using the computer program COMBIN. Each family was ascertained without deliberate selection for multiplex families, and most families were completely typed for HLA-B, HLA-DR, and properdin factor B (Bf). There were 186 families with normal parents, 44 families with one affected parent, and no families with two affected parents. The computer program COMBIN evaluates evidence for a major locus of disease susceptibility, linkage of the major locus to a known genetic marker locus, linkage disequilibrium between the marker haplotypes and disease susceptibility, pleiotropic effects, and presence of an unlinked modifier. The parameters of COMBIN are T, Q, and D, representing the displacement, gene frequency of the IDDM allele, and dominance, respectively, of the major locus--and TM, QM, and DM being the analogous parameters of the modifier. In addition, the recombination fraction, theta, between the IDDM locus and HLA as well as the coupling frequencies are estimated. Finally, COMBIN simultaneously performs segregation and linkage analysis, with the optimal model being adjusted by the fit to the haplotype sharing distribution of IDDM. The results of these analyses indicated that the best-fitting genetic model of diabetic susceptibility appears to be a single major locus with near recessivity on a scale of standardized genetic liability, with gene frequency of the IDDM susceptibility allele of approximately 14%. In addition, the recombination fraction between the major locus and HLA is zero in all models; that is, for the B-BF-DR haplotype, the IDDM locus is tightly linked, probably (according to data from previous studies) to HLA-DR. Information determined by magnitude of coupling frequencies indicated that there is significant positive linkage disequilibrium with the haplotypes B8-BfS-DR4 and B15-BfS-DR4, significant negative linkage disequilibrium with B7-BfS-DR2, and intermediate disequilibrium for B8-BfS-DR3, B18-BfF1-DR3, and B40-BfS-DR4. Significant evidence in favor of an unlinked (to HLA) modifier (either single major locus or polygenes) could not be demonstrated. In conclusion, genetic susceptibility to IDDM appears to be most consistent with a single major locus with near recessivity that is tightly linked to HLA.

Chromosome Mapping↗

DR2+ haplotypes in insulin-dependent diabetes: analysis of DNA restriction fragment length polymorphisms.

Insulin-dependent diabetes (IDD) is strongly associated with certain HLA class II (Ia) antigens. The frequency of DR2 is significantly reduced in IDD; among DR2+ patients, the frequency of the subtype specificity Dw2 defined with homozygous typing cells (HTCs) is significantly reduced compared to DR2+ controls, and the specificity LD-MN2, which we have defined using primed lymphocyte typing reagents, is significantly increased. We have studied DNA restriction fragment length polymorphisms (RFLP) of DR2-LD-MN2+ individuals and homozygous typing cells carrying specificities antigenically related to LD-MN2. Using a number of different restriction enzymes, a characteristic pattern of fragments could be defined for DR2-LD-MN2 using both DQ beta and DR beta cDNA probes. This pattern was shared with some but not all of the antigenically related HTCs, and was distinct from that of DR2-Dw2. The RFLP pattern of DR2-LD-MN2 obtained with the DQ beta probe is identical, except for one band, to that of DR1-Dw1, suggesting that at least some part of the DQ region is identical in these two haplotypes. These results indicate that analysis of RFLP patterns can be used to help identify the genetic regions and, eventually, genes most important in the association of HLA and IDD.

Alleles↗

Gm, Km, and HLA in insulin-dependent type I diabetes mellitus. A log-linear analysis of association.

Two hundred sixty families, in which at least one family member had insulin-dependent (type I) diabetes mellitus (IDDM), were typed for HLA antigens and the Gm and Km allotypes. Frequencies of Gm and Km allotypes in the diabetic subjects were compared with family controls (oldest nondiabetic sibling within a family). There were no significant differences between patients and controls for either Gm or Km allotype frequencies considered individually. When the log-linear model was used to analyze subjects and sibling controls, three significant findings emerged. First, there was a significant HLA-Gm interaction, indicating nonrandom segregation of HLA antigens with Gm allotypes, regardless of disease status. Second, there was, as expected, a significant HLA-IDDM interaction, indicating that HLA type is nonrandom with respect to IDDM status. Third, there was a significant HLA-sex-Gm-IDDM interaction, indicating that combinations of HLA antigens, Gm allotypes, and sex may play an important role in defining risk for IDDM. Thus, Gm and sex interacting with HLA may reflect the influence of an unlinked modifier previously hypothesized for IDDM pathogenesis.

Adolescent↗

Insulin-dependent diabetes--associated HLA-D region encoded determinants.

We have studied the relative frequency of Dw specificities (defined with homozygous typing cells or primed LD (lymphocyte defined) typing reagents) associated with DR4 and DR2 in the normal and insulin-dependent diabetic population. Our findings demonstrate that there is a highly significantly increased frequency of Dw4 in DR4 positive diabetics as compared with normals and a significantly decreased frequency of Dw2 and Dw12 in the few DR2 positive insulin-dependent diabetics that we have found. In addition, we have used PLT reagents to define a new LD specificity, LD-MN2, that is associated with DR2 and is found significantly more frequently in DR2+ IDD patients than in DR2+ normals. These results suggest that determinants of import in the association between HLA-D and IDD may be more closely related to Dw than to DR.

Adolescent↗

Skeletal muscle basement membrane in maturity-onset diabetes in the young.

We have studied skeletal muscle capillary basement membrane width (CBMW) and intensity of skeletal muscle extracellular basement membrane staining for albumin and IgG in eight families with maturity-onset diabetes in the young (MODY). Ninety-two MODY patients were identified. Sixty-three of these patients, 33 relatives with nondiagnostic oral glucose tolerance studies, and 61 normoglycemic relatives were studied for glucose and insulin. Twenty-six of these MODY patients, 20 normoglycemic relatives, and 16 unrelated normal controls had skeletal muscle capillary morphologic studies. The muscle capillary basement membrane was significantly increased in MODY patients younger than 40 yr when compared with unrelated normal subjects and relatives of the same age (P less than 0.001). However, in these families, the CBMW of MODY patients showed no significant thickening with age (slope = 0.45, P less than 0.14), as expected and seen in the normal subjects and in the normoglycemic relatives of the patients (slope = 1.21, P less than 0.001). The slope derived from the linear regression of age and CBMW in MODY patients (0.45 +/- 0.29) was significantly less (P less than 0.05) than that of the nondiabetic subjects (1.21 +/- 0.19). The mean intensity of skeletal muscle extracellular basement membrane staining for albumin was higher in MODY patients (1.1 +/- 0.15) than in unrelated normal subjects (0.7 +/- 0.1, P less than 0.025) and normal MODY family members (0.6 +/- 0.08, P less than 0.01). The unexpected absence of basement membrane thickening with age in the MODY patients may explain the paucity of vascular complications that have been reported by some.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Complement and HLA. Further definition of high-risk haplotypes in insulin-dependent diabetes.

The families of 41 probands with type I (insulin-dependent) diabetes mellitus (IDDM) were typed for HLA-A, HLA-B, and HLA-DR antigens in addition to the complement polymorphisms C2, C4A, C4B, and Bf. All of these loci are encoded on the short arm of human chromosome 6 in a narrow region. Alleles at HLA-B (8, 15, 18, and 40), HLA-DR (3 and 4), and Bf (F1) have been associated with increased relative risk (RR) for IDDM, while HLA-B7 and HLA-DR2 have been associated with decreased RR for IDDM. This study confirms those significant risks in addition to confirming increased risk for the null (silent) allele for C4A (C4AQ0) and a rare C4B variant (C4B2.9). The significantly associated antigens (alleles) and risks were: HLA-B8 (RR = 3.1), HLA-DR3 (RR = 5.2), HLA-DR4 (RR = 4.3), and BfF1 (RR = 7.1), in addition to C4AQ0 (RR = 2.8) and C4B2.9 (RR = 12.6). Significantly low risk was associated only with HLA-DR2 (RR = 0.1). In a recent study, we defined five high-risk haplotypes that were determined solely by HLA-B, Bf, and HLA-DR (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4). By inclusion of information from the complement polymorphism, we have defined in greater detail three of these five high-risk haplotypes. One previously identified haplotype (B40-BfS-DR4) showed no complement clustering, while the rare high-risk haplotype (B8-BfS-DR4) was seen only once in this smaller sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Albumin deposition in dermal capillary basement membrane in parents of type 1 (insulin-dependent) diabetic patients.

Skin biopsies were performed to examine dermal capillary basement membranes for albumin by immunofluorescence microscopy in children and young adults with Type 1 (insulin-dependent) diabetes from simplex and multiplex families, their non-diabetic parents and control subjects. Circumferential vessel staining for albumin was 12.0 +/- 14.4% (mean +/- SD) in diabetic patients from multiplex families, 18.8 +/- 20.0% in diabetic patients from simplex families, and 18.5 +/- 24.2% in unaffected parents from simplex families. These values were significantly higher (p less than 0.005) than those obtained in unaffected parents from multiplex families (0.4 +/- 0.9%) or control subjects (0.8 +/- 1.7%). There was no statistically significant difference between Type 1 diabetic probands from simplex or multiplex families and unaffected parents from simplex families. In the simplex families, positive capillary staining for albumin was present only in parents from families in which the diabetic proband had positive staining. In the parents, the presence of dermal capillary staining for albumin did not correlate with an abnormal glucose tolerance test or the presence of cytoplasmic islet cell antibodies. These observations suggest an abnormality in the dermal capillary basement membrane in some unaffected parents of Type 1 diabetic patients from simplex families.

Adolescent↗

Toluidine blue staining in the detection of oral precancerous and malignant lesions.

One hundred thirty-two consecutive patients suspected of having malignant or precancerous oral lesions were studied by comparing toluidine blue dye uptake clinically with a simultaneous biopsy. The histopathologic diagnosis confirmed 57 squamous carcinomas, 42 epithelial dysplasias, and 33 benign mucosal changes. Overall accuracy of the toluidine blue uptake was 91%. In the dysplastic and malignant lesions the false negatives were 2%, and there were 30% false positives in the benign lesions. It was concluded that toluidine blue staining is a useful adjunct to careful examination, clinical judgment, and biopsy.

Adult↗

The Minnesota Diabetes Complications Clinical Trial cognitive functions under long-term maximized and standard metabolic controls.

We have studied memory (Wechsler Memory Scale) and mood states in 20 insulin dependent diabetics under maximized metabolic control (treated with multiple insulin injections daily or insulin pumps) and 12 patients under standard control (treated with one or more injections of insulin daily). Both groups of patients have been enrolled in the Minnesota Diabetes Complications Clinical Trial for two years or longer. The patients in the maximized control group (mean +/- SD) blood glucose 130 +/- 9 mg/dl) had hypoglycemic episodes much more frequently than the patients in the standard control group (mean +/- SD blood glucose 242 +/- 22 mg/dl). Both groups of patients had normal cognitive functions, including a few patients with numerous hypoglycemic episodes. Only one patient who developed a hypoglycemic coma for several weeks has had lasting abnormal cognitive functions including a few patients with numerous hypoglycemic episodes. We conclude that long-term maximized diabetic control (at least 2 years), although not devoid of danger, does not seem to affect cognitive functions in the patients tested according to the parameters used.

Adult↗