Search PubMed⌕ Search

Biomedical subjects

P Rubinstein

Publications and source records attributed to P Rubinstein.

At least 127 records · Page 7Linked to original sources
PubMed1983

Effect of population associations and reduced penetrance on observed and expected genotype frequencies in a simple genetic model: application to HLA and insulin dependent diabetes mellitus.

The observed and Hardy--Weinberg-expected frequencies for (HLA) marker heterozygotes in a disease population are calculated where it is assumed that the disease is caused by either homozygosity or heterozygosity (with reduced pentrance) for a disease susceptibility allele at a disease locus, that allele being positively associated with both of the relevant alleles at the marker locus (the single susceptibility allele model of Svejgaard & Ryder, 1981). It is shown that the observed frequency is always less than or equal to the H-W expectation, with the (observed/expected) ratio decreasing as the degree of dominance increases.

Alleles↗
PubMed1983

Genetic polymorphism of human C4-binding protein.

Two different forms of human C4-bp, C4-bp A and C4-bp B, have been identified by isoelectric focusing (IEF) of neuraminidase-treated EDTA-plasma samples. Family studies demonstrate Mendelian segregation of these forms, indicating that they are under gentic control. This conclusion is supported by IEF analysis of the two variants purified by affinity chromatography. Under completely denaturing conditions, C4-bp B was found to be composed of two subunits that focused at different pH, whereas C4-bp A contains only the more basic one. These results suggest that a single autosomal locus with at least two codominant alleles coding for the subunits controls the IEF variation of C4-bp in humans. The allele designated C4BP*1 codes for a subunit that, after neuraminidase treatment, focuses at pH = 6.65. The allele C4BP*2 codes for a different subunit that focuses at pH = 6.60. The C4-bp A phenotype corresponds to the genotype C4BP*1,C4BP*1 and the phenotype C4-bp B to the genotype C4BP*1,C4BP*2. The phenotype corresponding to the C4BP*2,C4BP*2 homozygous genotype has not been encountered thus far. Initial linkage data indicate that the C4BP locus is not closely linked to either the HLA or to the C3 loci.

Animals↗
PubMed1982

Familial renal amyloidosis: case reports and genetic studies.

Rapidly progressive biopsy-proved renal amyloidosis developed in three brothers, aged 49, 52, and 55, or Irish-American origin. None had evidence of a plasma cell dyscrasia, a monoclonal serum or urine protein, or any underlying chronic disease. Immunoperoxidase staining of one pulmonary and one renal biopsy specimen was negative for Amyloid A (AA), Amyloid L (AL), and prealbumin. To investigate factors that might play a role in the disease, the subjects and 21 relatives were typed for antigens of the A, B, C, and DR loci and the linked marker genes for factor B and glyoxalase. The ability of macrophages to degrade serum amyloid A (SAA) [1] was examined. One brother yielded an intermediate AA-like produce similar to what is seen in most patients with AA or AL amyloidosis and 40 percent of normal subjects. The other two degraded SAA completely to small peptides. Analysis of the families revealed first that the disease was not linked to the major histocompatibility complex. We were unable to demonstrate a genetic relationship between processing of SAA by peripheral mononuclear cells and the human leukocyte antigen locus. Finally, the pattern of SAA degradation was not associated with the development of the disease.

Adult↗
PubMed1982

Highly polymorphic DNA site D14S1 maps to the region of Burkitt lymphoma translocation and is closely linked to the heavy chain gamma 1 immunoglobulin locus.

Using a phage lambda Charon 4A recombinant DNA clone (lambdaCH4A-rHs18) from a human genomic library, Wyman and White detected a multiallelic common polymorphism at an EcoRI site (D14S1) flanking the DNA region homologous to the probe [Wyman, A. R. & White, R. (1980) Proc. Natl. Acad. Sci. USA 77, 6754-6758]. Subsequent studies, carried out with the cell hybrid approach and the use of a subclonal derivative (pAW101) from lambdaCH4A-rHs18 have assigned this locus to autosome 14 between 14q21 and 14qter [De Martinville, B., Wyman, A. R., White, R. & Franke, U. (1982) Am. J. Hum. Gen. 34, 216-226]. The data presented here permit the precise mapping of this locus to the subtelomeric region of autosome 14, below band 14q32, in close proximity to the heavy chain gamma1 immunoglobulin locus. These conclusions are supported by three independent lines of evidence, including studies on gene dosage, somatic cell hybrids, and pedigree analysis. Our results are in agreement with the recent assignment of the heavy chain gamma1 immunoglobulin locus to band 14q32 [Kirsch, I. R., Morton, C. C., Nakahara, K. & Leder, P. (1982) Science 216, 301-303] and are consistent with the generally held contention that one unit of meiotic recombination corresponds approximately to one million base pairs. It is to be expected that the location of the highly polymorphic D14S1 site at a measurable distance from the cluster of the heavy chain genes will provide new opportunities for a genetic approach to the question of the specific gene order within the cluster, its possible individual variation, and its biological significance in normal development and disease. It is worthwhile to point out that such a highly polymorphic DNA sequence is located in the same chromosomal region where so much somatic rearrangement goes on normally (i.e., switch region between classes of heavy chain constant region genes) and which is involved with de novo translocations associated with malignancies.

Burkitt Lymphoma↗
PubMed1982

HLA antigens, cytoplasmic islet cell antibodies, and carbohydrate tolerance in families of children with insulin-dependent diabetes mellitus.

Cytoplasmic pancreatic islet cell antibodies were found in 21% of 244 unaffected first degree relatives of type I diabetic patients. Twenty-five percent of HLA-identical, 35% of HLA-haploidentical, 16% of HLA-nonidentical siblings, and 14% of parents were ICA-positive. In the HLA-identical sibs, irrespective of ICA, and in the 18 ICA-positive parents but not the other groups, increased plasma glucose levels were observed after the administration of glucose. In most children, these were associated with reduced insulin levels, while in the adults elevated insulin responses were noted. In 48% of the ICA-positive children and 84% of the ICA-positive parents, other evidence of "autoimmunity" was obtained either by history or by testing for specific autoantibodies. Two of the originally unaffected HLA-identical and ICA-positive siblings developed diabetes during the course of the study. These findings, plus previously reported data in families with two diabetic sibs demonstrating that the empiric risk for developing IDDM is of the order of 30% for HLA-identical sibs but less than 5% for those that are HLA-haploidentical, suggest that HLA-identity may be a useful predictor of potential type I diabetes. The presence of ICA may, at times, portend the need for future antidiabetic therapy but prospective studies must be continued to fully elucidate this relationship.

Adolescent↗
PubMed1982

The HLA system in congenital rubella patients with and without diabetes.

The HLA antigens of 173 patients with the congenital rubella syndrome (CR) are reported. Twenty-one of these patients are also clinically diabetic, and among them the frequencies of the HLA antigens DR2 and DR3 are significantly lower and higher, respectively, than in CR patients without diabetes or in controls. These data suggest that the genes that control susceptibility to type I or insulin-dependent diabetes mellitus are necessary for the development of glucose intolerance in CR patients.

Adolescent↗
PubMed1982

Disseminated Kaposi's sarcoma in homosexual men.

Nineteen cases from an epidemic of disseminated Kaposi's sarcoma in homosexual men were studied by clinical, virologic, immunologic, and genetic methods. The patients were all male homosexuals ranging in age from 29 to 52 years, with histories of multiple sexually transmitted diseases and exposure to both prescription and recreational drugs. Sites of disease included skin (16 of 19 patients), lymph nodes (13 patients), gastrointestinal tract (12 patients), spleen (three patients), and lung (one patient). Most patients had elevated levels of serum immunoglobins, positive antibody titers to hepatitis A and B virus, cytomegalovirus and Epstein-Barr virus, and impairment of cell-mediated immunologic reactions. The frequency of HLA-DR5 in these patients was significantly elevated. Two of the 19 patients died. Although the precise cause of this epidemic is unknown, it is likely that a genetic predisposition, an acquired immunoregulatory defect, and one or more infectious agents and drugs may be involved.

Adult↗
PubMed1981

Glyoxalase 1 (GLO) in the chicken: genetic variation and lack of linkage to the MHC.

Electrophoretic variation of glyoxalase 1 (GLO) has been detected in chicken red-cell lysates. Three phenotypes are shown to be inherited through a diallelic system, just as in humans and mice. The chicken GLO phenotype differ from their mammalian counterparts in that one of the homozygotes is devoid of GLO activity. The heterozygote produces two bands, while the other homozygote yields a single band of GLO activity with mobility equal to the faster of these two bands. In noninbred White Leghorn birds, the GLO2 allele occurred significantly more often in birds homozygous for the B1 allele at the chicken MHC than in those homozygous for B19, suggesting that the products of these loci may have population associations in the chicken. Absence of close linkage between the GLO and B loci was, however, demonstrated by appropriate test crosses.

Animals↗
PubMed1981

HLA antigens and islet cell antibodies in gestational diabetes.

The HLA antigens of 136 patients with gestational diabetes are compared with control populations. No significant variations are observed in their frequencies, particularly for those antigens associated with Type 1 diabetes mellitus. Islet cell antibodies have also been studied in the serum of 52 of these patients and 20 of them were positive, whereas only one of 37 pregnant nondiabetic women had such antibodies (chi 2 = 15.2). A very high association between ICA and DR3 and DR4 was encountered (chi 2 = 17, with two df); half of the patients positive for either one of these antigens were ICA positive. These results indicate that ICA associates equally with DR3 and DR4, against the hypothesis that this expression of autoimmunity is more a characteristic of DR3- than of DR4-associated genetic susceptibility. These patients will be followed to determine if the ICA+ individuals are at increased risk for the development of insulin-dependent diabetes.

Adult↗
PubMed1981

Genetics of Type I diabetes mellitus: a single, recessive predisposition gene mapping between HLA-B and GLO. With an appendix on the estimation of selection bias.

Three different published sets of HLA-typed families of juvenile diabetes mellitus (JDM) patients have been analyzed. There was no significant genetic heterogeneity between them according to the criterion of Morton, and the total material was analyzed on the assumption of a single recessive (JDM-P) gene with incomplete penetrance. The analysis, carried out with the NYLIP program modified to account for penetrance less than 1 and for selection bias, yields highly significant lod scores for linkage between HLA and JDM-P, with a maximum value of 7.40 at theta = .05 +/- .03. The segregation of HLA and GLO in five affected sib pairs, in which one of the sibs carries an HLA/GLO recombinant, places JDM-P closer to HLA than the GLO locus: four of these five pairs are HLA-identical and GLO-different, in agreement with the conclusions of the formal linkage analysis. The data from these three independent sets of families are therefore consistent with our earlier claim that JDM is inherited as a recessive trait closely linked to HLA with reduced penetrance, and its analysis does not require more complicated genetic models.

Chromosome Mapping↗
PubMed1980

The effect of association of genetic factors on relative risk.

We have examined the numerical properties of relative risk (RR) estimates under the conditions of gene frequency and genetic association (delta) that generally obtain for the different HLA loci. It is found that significant RR may be created solely by the existence of positive delta between the disease susceptibility gene and a specific allele at the marker (e.g. HLA) locus. It is shown further, that the value of RR is strongly affected by the gene frequencies and not only by the corresponding delta. If positive delta exists between one disease susceptibility gene and two HLA haplotypes, the RR estimates will usually be highest for the corresponding heterozygote, intermediate for the two homozygotes and lowest for the other carrier phenotypes. This model was found to be perfectly compatible with the situation encountered in the case of juvenile diabetes mellitus and shows that 'overdominance' is not required to account for the excessive RR found in some populations for certain HLA heterozygous classes.

Alleles↗