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P Rubinstein

Publications and source records attributed to P Rubinstein.

At least 109 records · Page 6Linked to original sources
PubMed1985

Triad of markers for identifying children at high risk of developing insulin-dependent diabetes mellitus.

A longitudinal investigation was conducted from 1977 to 1984 on 178 families in which one or more of the children had insulin-dependent diabetes mellitus. Of 351 nondiabetic sibs followed up for an average of 54 months, ten have, thus far, become diabetic. Eight sibs were HLA identical to their diabetic proband and nine had HLA-DR3 and/or HLA-DR4. Islet cell surface antibody and islet cell cytoplasmic antibody were found from two to 74 months before the onset of clinical diabetes in 100% and 90%, respectively, of the children. A decrease in insulin secretion was observed in all of these children on entry into the study and was detected in the absence of elevated plasma glucose concentrations. The data suggest that the triad of HLA identity, pancreatic islet cell antibodies, and depressed insulin secretion identifies those sibs who are at high risk of developing insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1985

Human genes for three complement components that regulate the activation of C3 are tightly linked.

A new cluster of complement component genes, including C4BP, C3bR, and FH, is described. Family segregation data indicate that FH is linked to the genes for C4-bp and C4bR, previously reported to be linked and to maintain linkage disequilibrium. This cluster is not linked to the major histocompatibility complex, which contains the genes for the complement components, C4, C2, and factor B, or to the C3 locus. These data further suggest that the organization of genes for functionally related proteins in clusters may be a rule for the complement system.

Carrier Proteins↗
PubMed1985

Does the mouse C4-binding protein gene (C4BP) map in the H-2 region?

A previous study on the genetics of mouse C4-binding protein (C4-bp) indicated the existence of a genetic polymorphism. Two genetic variants were reported and their segregation used to determine the mapping position of the C4BP locus to the H-2D-Qa interval of the mouse H-2 system. We show here, however, that purified C4-bp does not display the previously reported polymorphism. The mapping position of C4BP in the mouse therefore remains undetermined.

Animals↗
PubMed1985

Radioimmunoassay and enzyme-linked immunoassay of antibodies directed against lymphadenopathy-associated virus (LAV) proteins larger than the core protein (P24).

The acquired immunodeficiency syndrome (AIDS) may be transmitted by blood transfusions and by blood products from donors who have been infected with the lymphadenopathy-associated virus (LAV). Such donors may generally be identified on the basis of a positive test for antibodies-against LAV proteins. We have already described an anti-LAV assay based on the use of crude virus-infected tissue culture medium, which avoids elaborate, expensive and potentially hazardous virus purification steps. This test was operationally specific for antibodies to the approximately 24 kD core protein of the virus (P24; Neurath et al. J. Virol. Methods 11, 75, 1985). Molecular exclusion chromatography of crude LAV antigen preparations allows separation of most of P24 from larger proteins of LAV (PL). PL and 125I- or beta-lactamase-labeled anti-LAV were used as reagents for radioimmunoassay (RIA)--or enzyme-linked immunoassay (ELISA)--inhibition tests to detect antibodies directed predominantly against PL (anti-PL). Among 257 individuals belonging to groups at high risk of developing AIDS, 117 (45.5%) were positive for anti-PL and 108 (42%) for anti-P24, respectively. The 2 individuals among 600 random blood donors found to be anti-P24-positive in the preceding study also had anti-PL in their serum. Sera from 500 additional blood donors were screened for anti-PL and 1 of these was positive. The implication of these findings for screening of blood donors is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Radioimmunoassay and enzyme-linked immunoassay of antibodies to the core protein (P24) of human T-lymphotropic virus (HTLV III).

Human T-cell lymphotropic viruses designated HTLV III or LAV are considered to represent the causative agent(s) of the acquired immunodeficiency syndrome (AIDS). Individuals who have been infected with these viruses may generally be identified on the basis of a positive serological test for antibodies against the protein components of these viruses. Purified viruses or viral proteins have been utilized for developing such tests. Since AIDS may be transmitted by blood transfusion and by blood products, screening of donors for antibodies to HTLV III/LAV has become a necessity. Such screening may be facilitated by the application of assays based on the use of crude virus-infected tissue culture media avoiding elaborate, expensive and potentially hazardous virus purification steps. Serum specimens were mixed with an appropriate dilution of an HTLV III-infected tissue culture-derived fraction, obtained by precipitation with polyethylene glycol 6000 and treatment with Tween 80 and tri-n-butylphosphate (to disrupt virus particles), and incubated with polystyrene beads coated with antibodies to HTLV III/LAV (anti-HTLV III). Subsequently, washed beads were incubated with either 125I- or beta-lactamase-labeled anti-HTLV III. The radioactivity or enzymatic activity associated with the beads was proportionate to the quantity of HTLV III antigen originally added to the beads. The presence of anti-HTLV III in serum specimens resulted in decreased antigen binding and thus in decreased radioactivity or diminished beta-lactamase activity associated with the beads. The test was specific for antibodies to the approximately equal to 24 kDa core protein of HTLV III. The prevalence of these antibodies (given in parentheses) in distinct populations was as follows: random blood donors (0.33%); hemophiliacs (36.4%); random homosexual males (25.1%); homosexual males preselected on the basis of positive markers for infection with hepatitis B virus (50%); and those with persistent lymphadenopathy (70%).

Acquired Immunodeficiency Syndrome↗
PubMed1985

Choledochocele and recurrent pancreatitis. Diagnosis and surgical management.

A case history has been presented that reports a rare type III choledochal cyst (choledochocele) and describes the association of a choledochocele and recurrent acute pancreatitis. The most reliable diagnostic technique, as used in our patient and supported by our literature review, is endoscopic retrograde cholangiopancreatography. This case further supports surgical correction employing transduodenal sphincteroplasty. This procedure is highly recommended for management of the intramural choledochocele (type IIIc), especially when associated with recurrent pancreatitis. Finally, patients who present with recurrent pancreatitis without the usual historical or diagnostic findings of biliary tract or alcoholic disease should have a choledochocele included in the differential diagnosis.

Acute Disease↗
PubMed1985

Two blood group M epitopes disclosed by monoclonal antibodies.

Two cloned mouse hybridomas, designated G8 and E3, produced anti-M of immunoglobulin classes IgG2b and IgG1, respectively. No discrepancies were observed in testing over 5,000 normal donor blood samples with appropriately diluted G8 and E3 culture supernatant fluids in parallel with rabbit anti-M and anti-N typing reagents. The specificity and titer of antibodies produced by G8 and E3 were minimally affected by changes in temperature (37 degrees C, 22 degrees C, 4 degrees C). G8 and E3 showed reduced activity with type MM red cells that had been treated with either neuraminidase or papain, but differences were observed in the susceptibility of the respective epitopes to treatment with neuraminidase. Furthermore, G8 and E3 exhibited different specificities when used to test the red cells of nonhuman primates and erythrocytes of the rare MgMg human blood type. These results indicate the existence of at least two M antigen epitopes.

Amino Acid Sequence↗
PubMed1985

Cytotoxic islet cell surface antibodies (ICSA) in patients with type I diabetes and their first-degree relatives.

We describe a nonradioactive microcytotoxicity assay for ICSA using a cloned rat insulinoma cell line. This assay system had good reproducibility (r = 0.93) and was suitable for the study of large numbers of samples. The following results were obtained by testing the sera of 111 patients with IDDM (type I diabetes) and all of their first-degree relatives. (1) Thirty-five percent of IDDM patients had ICSA, as compared with only 2% of healthy controls. (2) ICSA was found more frequently in patients within 2 yr of onset (45%) than in those with disease for longer than 2 yr (27%) (P less than 0.05). (3) The prevalence of ICSA was associated with the presence of cytoplasmic islet cell antibodies (ICA) (P less than 0.05). (4) No association was found between the prevalence of ICSA and specific HLA-DR alleles. Association with the HLA haplotypes in families with ICSA-positive probands, on the other hand, is suggested although not proven by these data. (5) Among the nondiabetic relatives of IDDM patients, 5% of the parents and 14% of the sibs had ICSA. Increased prevalence of ICSA occurred in the unaffected sibs of ICSA-positive probands (31%) but not in those of ICSA-negative probands (4%) (P less than 0.001); in fact, the relatives of ICSA-negative probands had ICSA with a frequency not higher than in unrelated controls. (6) Female relatives of ICSA-positive probands were more often ICSA-positive than males, but no such difference was found among probands. (7) In multiplex sibships, ICSA were not associated with disease in the sibs.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1985

Human erythroid progenitor cells express Rhesus antigens.

The expression of Rhesus antigens on hematopoietic progenitor cells was studied using monoclonal antibodies. Because these antibodies are not capable of lysing mature red blood cells in a complement-dependent cytotoxicity assay, fluorescence-activated cell sorting was performed. Using the monoclonal anti-Rh 29 antibody B10, 68% +/- 6% of the mature erythroid progenitor cells (CFU-E) were sorted into the positive fraction, while only 2% +/- 1% of the relatively immature erythroid progenitor cells (BFU-E), and 3% +/- 1% of the granulocyte-macrophage progenitor cells (CFU-GM) were cultured from this same fraction. Thus up to a 15-fold enrichment of CFU-E could be obtained. In two experiments more than 4% of the cells in the positive fraction consisted of CFU-E; in one experiment even more than 7% did. Using fractionated cell sorting, the Rhesus antigens appeared to have a lower density on CFU-E than HLA-DR determinants. Antibodies against the Rhesus antigens can be applied to enrich erythroid-committed stem cells and to separate mature from immature erythroid progenitor cells.

Antibodies, Monoclonal↗
PubMed1985

Therapeutic trial of interferon-gamma in patients with epidemic Kaposi's sarcoma.

An epidemic form of Kaposi's sarcoma associated with the acquired immune deficiency syndrome has been recently described. Seven homosexual men with biopsy-documented epidemic Kaposi's sarcoma were treated with a human interferon-gamma preparation. All patients had generalized disease. Only one patient had received prior chemotherapy, and one other patient had recovered from a prior opportunistic infection. Interferon-gamma was administered in a dose of 500,000 U intramuscularly daily, with two 10-day induction courses, separated by a 2-week medication-free period. This was followed by maintenance therapy in the same dose twice weekly. Toxicities consisted of a flu-like illness with high fevers, shaking chills, myalgias, and arthralgias. There were no complete or partial responses. All patients exhibited disease progression, with a rapid progression of previously stable disease necessitating discontinuation of therapy in three patients. We conclude that low doses of this human interferon-gamma preparation are ineffective in epidemic Kaposi's sarcoma.

Adult↗
PubMed1985

High frequency of nonclassical steroid 21-hydroxylase deficiency.

Nonclassical steroid 21-hydroxylase deficiency is an autosomal recessive disorder that is defined by clinical and hormonal criteria that distinguishes it from the classical 21-hydroxylase deficiency. No estimates of the gene frequency of nonclassical 21-hydroxylase deficiency, also called attenuated, late-onset, acquired, and cryptic adrenal hyperplasia, have been published thus far. Here, we have used HLA-B genotype data in families containing multiple members affected with nonclassical 21-hydroxylase deficiency together with the results of quantitative hormonal tests to arrive at estimates of gene and disease frequencies for this disorder. We found nonclassical 21-hydroxylase deficiency to be a far more common disorder than classical 21-hydroxylase deficiency, which occurs in 1/8,000 births. The prevalence of the disease in Ashkenazi Jews was 3.7%; in Hispanics, 1.9%; in Yugoslavs, 1.6%; in Italians, 0.3%; and in the diverse Caucasian population, 0.1%. The gene for nonclassical 21-hydroxylase deficiency is in genetic linkage disequilibrium with HLA-B14 in Ashkenazi Jews, Hispanics, and Italians, but not in Yugoslavs or in a diverse, non-Jewish, Caucasian group. The penetrance of nonclassical 21-hydroxylase deficiency gene in the HLA-B14 containing haplotypes was incomplete. Thus, nonclassical 21-hydroxylase deficiency is probably the most frequent autosomal recessive genetic disorder in man and is especially frequent in Ashkenazi Jews, Hispanics, Italians, and Yugoslavs.

Adrenal Hyperplasia, Congenital↗
PubMed1984

High resolution isoelectric focusing of immunoprecipitated proteins under denaturing conditions. A simple analytical method applied to the study of complement component polymorphisms.

A simple analytical method for the study of structural protein polymorphisms is described. It consists of the immunoprecipitation of non-radiolabeled proteins using monospecific polyclonal antibodies followed by isoelectric focusing (IEF) under completely denaturing conditions in vertical polyacrylamide slab gels. The method uses small amounts of sample (usually unfractionated plasma or serum), requires no sophisticated equipment and allows the screening of large numbers of samples with comparatively small effort. This method has been applied in the identification of 2 human complement-component polymorphisms, C4-binding protein (C4-bp) and factor H (beta 1H).

Antigen-Antibody Reactions↗
PubMed1984

Evidence for linkage between the loci coding for the binding protein for the fourth component of human complement (C4BP) and for the C3b/C4b receptor.

Three pedigrees informative for the segregation of genetic variants of the binding protein for the fourth component of complement (C4BP) and C3b/C4b receptor (C3bR) have been identified. There were 10 informative meioses with no recombinants, indicating a close linkage between the loci encoding C4BP and C3bR, C4BP and C3bR [maximum lod (logarithm of odds of linkage) score: 2.4 at recombinant fraction = 0.0]. In addition, in the four unrelated individuals who were doubly heterozygous (C4BP*1, C4BP*2, C3bR*A, C3bR*B), the infrequent allele C4BP*2 segregated together with the uncommon allele C3bR*B, supporting the hypothesis of linkage between C4BP and C3bR and suggesting that linkage disequilibrium exists between these particular alleles. We conclude that the loci encoding C3bR and C4BP, two functionally related molecules, are linked.

Alleles↗
PubMed1984

Kaposi's sarcoma in homosexual men. A seroepidemiologic case-control study.

The cases of 20 male homosexuals with Kaposi's sarcoma and the acquired immunodeficiency syndrome were compared with those of 40 age- and race-matched male homosexual controls. Patients with Kaposi's sarcoma had lower OKT4/OKT8 (T-helper/T-suppressor) ratios than controls, due to smaller numbers of OKT4 cells. Serum IgG concentrations and antibody titers to cytomegalovirus in patients exceeded those in controls, but patients had lower antibody titers to Epstein-Barr virus. Logistic regression analysis comparing patients with controls showed significant relative risks for Kaposi's sarcoma associated with the number of partners per month in receptive anal-genital intercourse, occasions per month of " fisting ," and cytomegalovirus antibody titers. Cytomegalovirus titers also were inversely correlated with OKT4 cell concentrations in the control group. Significantly greater OKT4 cell concentrations were found at diagnosis in HLA-DR5-positive patients than in HLA-DR5-negative patients. Patients who have HLA-DR5 may express disease at lesser degrees of immunodeficiency than HLA-DR5-negative patients.

Adult↗
PubMed1984

Genetic polymorphism of human factor H (beta 1H).

Human Factor H (beta 1H) was found to be polymorphic after neuraminidase treatment and isoelectric focusing (IEF) under completely denaturing conditions. Three variants, FH 1, FH 2, and FH 3, were identified in a sample population of 81 unrelated caucasoid individuals. Family studies demonstrated correct mendelian segregation of FH 1, FH 2, and FH 3. Our data indicate that these genetic variants of human Factor H are encoded by three codominant alleles, FH*1, FH*2, and FH*3, at a single autosomal locus FH. In the sample analyzed, the gene frequencies of FH*1, FH*2, and FH*3 were, respectively, 0.691, 0.302, and 0.006.

Alleles↗
PubMed1983

Results of large scale media antismoking campaign in Australia: North Coast "Quit for Life" programme.

A three community study was carried out in northern New South Wales, Australia, to determine the effectiveness of interventions via media and media plus community programmes in altering behaviours of life style, including smoking, dietary fat intake, and exercise. Results were analysed of one aspect of the "North Coast Healthy Lifestyle Programme" entitled "Quit for Life," which aimed at reducing cigarette smoking over a two year period. There was a significant decline in the prevalence of smoking in both test towns, ranging from 16% in younger men to 6% in older women. These were significantly greater than the declines in the control town. The declines were more sustained over the two year period in the town subjected to media plus community programmes.

Adolescent↗