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P Rubinstein

Publications and source records attributed to P Rubinstein.

At least 91 records · Page 5Linked to original sources
PubMed1987

Prevalence, clinical significance, and strain specificity of neutralizing antibody to the human immunodeficiency virus.

A semiautomated microtiter assay has been developed to quantitate neutralizing antibody to the human immunodeficiency virus. This assay has been found to be highly specific. Forty-four sera that were negative by enzyme-linked immunosorbent assay (ELISA) were tested under code: 42 were negative (less than 1:2), and 2 had titers of 1:2. By contrast, of 178 sera positive by western blot, 92.7% had detectable neutralizing antibody, and 12.5% had titers greater than or equal to 1:128. Neutralizing antibody titers correlated poorly with clinical diagnosis and T4/T8 ratios. Different isolates differed quantitatively in their sensitivity to neutralization by antibodies obtained from different patients; however, all strains tested so far have been neutralizable by all the sera tested. Neutralizing antibody titers correlated weakly, if at all, with direct or competition ELISA titers.

Antibodies, Viral↗
PubMed1987

A "new" HLA-C specificity, CSH-2, restricted to Oriental populations.

The high frequency of C-locus blank alleles in different races suggests the existence of an undetected antigen. We have identified a new C-locus antigen, tentatively named CSH-2, which is present in Oriental populations, but is apparently not present in Caucasoid, or Black populations. This new specificity was defined by a single strong monospecific antiserum, named ZHA114, which was obtained by planned immunization.

Asian People↗
PubMed1987

Monoclonal anti-K14 and anti-K2.

Mouse hybridoma clones have produced monoclonal antibodies directed against the K:14 and K:2 high-incidence antigens of the Kell blood group system. Two examples of anti-K14 were isolated, each arising from a separate fusion procedure. All three monoclonal antibodies are of the immunoglobulin class IgG1. Serological activity is consistent with that seen with human antibodies to high-incidence Kell system antigens, and their epitopes are destroyed, as usual, by 2-aminoethylisothiuronium bromide treatment. Specificity was further confirmed by adsorption and elution studies. Tests against nonhuman primate red cells demonstrated the expression of K:14 only by the great apes, whereas K:2 was present on all red cells tested. These findings emphasize the usefulness of monoclonal antibodies to elucidate the evolutionary patterns of blood group variants.

Animals↗
PubMed1987

Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations.

An alternative to Woolf's (1955) relative risk (RR) statistic is proposed for use in calculating the risk of disease in the presence of particular antigens or phenotypes. This alternative uses, as the control sample, the parental antigens or haplotypes not present in the affected child. The formulation of a haplotype relative risk (HRR) thus eliminates the problems of sampling from the same homogeneous population to form both the disease sample and an appropriate control. We show that, in families selected through a single affected individual, where transmission of the four parental haplotypes can be followed unambiguously, the mathematical expectation of the HRR is identical to that of the RR. Since the sample formed from the 'non-affected' parental haplotypes is clearly from the same population as the disease sample, the HRR thus provides a reliable alternative to the RR. A further advantage obtains when family data are being collected as part of a study since the control sample is then automatically contained in the family material. Data from studies of patients with insulin dependent diabetes mellitus (IDDM) are used to obtain an estimate of the risk to those with HLA antigens or phenotypes associated with IDDM using the HRR statistic. A comparison of the HRR's and RR's for these data is also presented.

Diabetes Mellitus, Type 1↗
PubMed1987

Detection of HIV antigen and specific antibodies to HIV core and envelope proteins in sera of patients with HIV infection.

The sera of well-characterized populations were examined for three markers of human immunodeficiency virus (HIV) infection; HIV antigen (HIV Ag), and antibodies to HIV envelope (gp41) and core (p24) proteins. Of 563 serum samples tested, 251 were from HIV-infected patients diagnosed as having AIDS manifested by opportunistic infections (AIDS-OI), AIDS-associated Kaposi's sarcoma (AIDS-KS), or AIDS-related complex (ARC). One hundred seventy-six specimens tested were from asymptomatic high-risk individuals, and 136 were from heterosexual control subjects or patients with non-AIDS-related disease. None of the 136 control individuals tested had HIV Ag or HIV antibodies to either p24 or gp41. Of the 427 HIV-seropositive individuals, 99% to 100% were positive for gp41 antibodies to HIV. In contrast, the seroprevalence of p24 antibodies to HIV varied from 23% to 83% and appeared to be inversely associated with the severity of the patients' clinical symptoms. When specimens were analyzed for the presence of HIV Ag, in seropositive individuals the prevalence rate for this marker was lowest (1.4%) in asymptomatic individuals and highest (50%) in the AIDS-OI diagnosed group. Also, 240 cases with AIDS-KS, AIDS-OI, and ARC and the group of asymptomatic high-risk individuals were analyzed for T helper/T lymphocytes (T4) cell number and T4/T8 ratio; only one (2.0%) HIV Ag-positive case showed a T4 cell number greater than 400 and a normal T4/T8 ratio. These studies appear to demonstrate a direct correlation between the presence of HIV Ag and the severity of clinical complications of HIV infection.

Antibodies, Viral↗
PubMed1986

Quantitative variations of the C3b/C4b receptor (CR1) in human erythrocytes are controlled by genes within the regulator of complement activation (RCA) gene cluster.

The genetic relationships of quantitative and structural variations of the C3b/C4b receptor (CR1) in human erythrocytes have been analyzed in informative families. Our results demonstrate the existence of multiple discrete quantitative variations of CR1 controlled by a locus, C3bRQ, closely linked to the CR1 structural locus, C3bR. Since the amounts of CR1 produced by each C3bR allele are shown to be independently regulated, we propose that a cis-acting genetic mechanism controls the level of expression of the C3bR alleles, and that this quantitative control plays a major, if not the sole, role in determining the total amounts of CR1 on normal human erythrocytes.

Alleles↗
PubMed1986

Functional modifications of alloreactive T cell clones infected with HTLV-I.

Two alloreactive T cell clones with anti-HLA-DR1 specificity showed significant alterations of cognitive and functional characteristics after infection with human T cell leukemia virus (HTLV-I). Similar to HTLV-I-infected lines derived from immunologically uncommitted lymphocytes, the transformed clones displayed blastogenic mixed lymphocyte culture (MLC) responses to cells carrying any of the allelic variants of human HLA-D/DR antigens, including self. Although these two clones were originally able to provide allospecific help only to B cells expressing the DR1 antigen, after infection with HTLV-I they stimulated B cells of any HLA-D/DR phenotype to produce immunoglobulin in cultures. The helper inducer activity of the transformed clones remained susceptible to the effect of monoclonal antibody anti-LDA1 that inhibits the helper function of normal human T cells. One of these clones (207TK), which before infection specifically killed DR1-positive target cells, lost its killing ability. The other clone (19TK) although originally noncytotoxic, acquired natural killer-like function after transformation. Study of the rearrangement of the genes coding for the beta-chain of the T cell antigen receptor revealed no differences between the wild (noninfected) and mutant (infected) clones. There was, however, an increased level of this message, as well as of the message encoded by the beta-chain gene of HLA-DR in the mutant clones. Such changes may be related to transacting transcriptional effects induced by the human T cell lymphotropic virus HTLV-I.

Antibodies, Monoclonal↗
PubMed1986

Kell blood group antigens are part of a 93,000-dalton red cell membrane protein.

Monospecific Kell blood group antibodies, of either human alloimmune or mouse monoclonal origin, react with a single surface-exposed protein of 93,000 daltons. Chymotryptic peptide maps of the 93,000-dalton protein isolated by antibodies of two different specificities (anti-K7 or anti-K14) indicate that Kell epitopes reside on the same protein. Kell protein is similar in size to band 3 protein but differs markedly in its tryptic and chymotryptic peptide maps, indicating that they are different proteins. In addition, sheep antibody to human band 3 does not react with Kell protein. Rabbit antibody to Kell protein reacts, by Western immunoblotting, with membrane proteins from Kell antigen positive red blood cells but not from those of a Ko (Kell null) cell. In intact red cells only a small portion of the Kell protein is available to lactoperoxidase-catalyzed iodination. Under nonreducing conditions Kell antigen is isolated not only as a 93,000-dalton protein but also as larger protein complexes ranging in size from above 200,000 to 115,000 daltons. Treatment of red cells with iodoacetamide, prior to isolation of Kell protein, reduces the amount of the very large complexes, but Kell protein occurs both as 115,000- and 93,000-dalton proteins.

Animals↗
PubMed1986

Herpes zoster: a possible early clinical sign for development of acquired immunodeficiency syndrome in high-risk individuals.

Zoster is uncommon before the age of 50 years in immunologically normal individuals, but it occurs with increased frequency in people who are immunosuppressed. A retrospective review of 300 patients with acquired immunodeficiency syndrome associated with Kaposi's sarcoma, revealed that 8% had prior zoster, a rate that is sevenfold greater than historic controls of the same age. We prospectively examined forty-eight patients, with no known immunodeficiency or signs of AIDS or AIDS related complex (ARC), who presented with zoster localized to the thoracic region. Forty-one patients had known risk factors for AIDS and thirty-five had antibody to the AIDS-associated virus (AAV) at the time of presentation. One seropositive subject had no known risk factors. Absolute lymphocyte counts, lymphocyte OKT4/OKT8 ratios, and lymphocyte mitogen responses were all depressed in subjects with antibody to AAV when compared with seronegative individuals. Seven of thirty-three AAV antibody-positive subjects, who could be followed longitudinally, developed AIDS from 1 to 28 months (mean = 13) after zoster. One antibody-negative subject seroconverted to become AAV seropositive 16 months after zoster and developed Kaposi's sarcoma 1 month later. These eight subjects had persistently low lymphocyte OKT4/OKT8 ratios and elevated beta-2 microglobulin. In patients at risk for AIDS, the occurrence of zoster may be one sign that heralds the marked depression of cellular immunity associated with AIDS or ARC.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Partial plasma exchange in patients with AIDS and Kaposi's sarcoma. Plasmapheresis in AIDS.

Intensive plasma exchange was performed in seven male homosexual patients with AIDS and Kaposi's sarcoma. Serial 1.2 plasma volume exchange procedures were performed three times a week for six weeks. In five of the patients, plasma replacement included gamma globulin in the form of plasma (two patients), or an IV IgG preparation (three patients). No changes in the mean number of helper-inducer or suppressor-cytotoxic cells were noted during the treatment period or the weeks following completion of the last procedure. The mean mitogenic response of the patients' lymphocytes to PHA increased by 32.4% during the course of the plasmapheresis procedures (p less than .05), but returned to baseline over the eight weeks following treatment. Mitogenic responsiveness to PWM did not significantly increase during the course of treatment. No regression of Kaposi's sarcoma lesions was found in any of the patients treated.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Thyroid autoantibodies in HLA-genotyped type 1 diabetic families: sex-limited DR5 association with thyroid microsomal antibody.

Thyroid autoantibodies are common in Type 1 diabetics and their first degree relatives and may be part of the autoimmune diathesis present within such families. We have measured the prevalence of microsomal (M-Ab) and thyroglobulin (Tg-Ab) autoantibodies in 84 HLA-typed families having a Type 1 diabetic child, using enzyme-linked immunosorbent assay techniques. Thyroid autoantibodies were detectable in 201/407 (49%) individuals in these families. Both autoantibodies were significantly more frequent in the subsets of parents, diabetic children and their non-diabetic siblings than in groups of control adults and children. The prevalence of these autoantibodies in the diabetic families was increased in both sexes with a female:male ratio of 1.4:1. Antigen DR5 was significantly associated with M-Ab production but only for male subjects (P = 0.005 after correction for the number of DR antigens tested). No significant associations were encountered for Tg-Ab. Within-family analyses indicated that thyroid autoantibodies occurred with increased prevalence in HLA-identical or haplo-identical siblings of autoantibody-positive index cases in comparison to control children. We conclude the DR association with thyroid autoantibody production in this diabetes-selected population was thyroiditis-related and not diabetes-related, and the DR5 association was restricted to males and the production of M-Ab. These data are consistent with the hypothesis that multiple genetic and non-genetic factors played a role in the high prevalence of thyroid autoantibodies in this population.

Adolescent↗
PubMed1986

Serology for automated cytotoxicity testing. II. Routine reading of HLA-typing using the Contrast Fluorescence Test.

We have previously reported on the "Contrast Fluorescence Test" (CFT), a method for the fluorimetric of living vs dead lymphocytes and have proposed its use in automated HLA typing. In this report, we present data obtained with the CFT in the evaluation of an automated system built around the Zonax instrument (Zeiss America, Inc.). 13,664 individual CFT results were read by the machine and compared with manual readings; assignment of HLA specificity was done independently but using the same logic by hand and by machine. Excellent correlation of the instrumented and manual serological readings and identical antigen assignments were observed.

Cell Survival↗
PubMed1986

Anti-insulin antibodies in children with type I diabetes mellitus. Genetic regulation of production and presence at diagnosis before insulin replacement.

We evaluated the production of antibodies against insulin in a genetically well-defined population. In the first study, 124 young patients with type I diabetes for longer than 6 mo were included. Anti-insulin antibodies were detected by polyethyleneglycol (PEG) precipitation after incubation of acidified, charcoal-stripped sera with 125I-labeled pork insulin and were expressed as microunits insulin bound per milliliter whole serum. For comparison, the patients were divided into six groups based on HLA DR antigens: 3/3, 3/-, 4/4, 4/-, 3/4, and -/-(-is non-DR3 or -DR4). The mean age of the patients was 14.7 +/- 0.5 yr; the duration of diabetes was 5.8 +/- 0.4 yr; and the glucose control, as measured by hemoglobin A1c was average (7.6 +/- 0.2%). There were no significant differences in any of these parameters among the patients in any of the HLA DR groups. Patients expressing DR3/3 had significantly lower insulin binding than the rest of the groups (2.5 +/- 0.4 vs. 13.6 +/- 1.4 microU/ml, P less than 0.0001). Patients with DR3/ - did not differ in insulin-binding capacity from the other groups. The type of insulin used for replacement was not correlated with the serum insulin-binding capacity. In a second study, sera from 48 children, newly diagnosed with type I diabetes, were examined for the presence of insulin binding before treatment with exogenous insulin and compared with sera from 80 children without diabetes or a family history of diabetes and from 103 unaffected HLA-identical or haploidentical siblings of a child with type I diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Excess of DR3/4 in type I diabetes. What does it portend?

The HLA-DR genotypes of 158 new type I diabetic probands from simplex families are compared with those of 43 multiply affected sibships. There were no significant differences in the gene frequencies of the insulin-dependent diabetes mellitus (IDDM)-associated alleles, DR3 and DR4, and whereas the DR3/4 heterozygotes were as frequent among simplex probands as among the first affected of multiplex sibships, subsequently affected sibs displayed lower frequencies of this genotype in this as well as in previously reported samples, indicating that the excessive risk associated with DR3/4 heterozygosity depends on the order of affection and thus on environmental factors. It is proposed that the penetrance of the susceptibility gene is enhanced by epistatic effects of this genotype and that this enhancement is strongest under conditions of low environmental liability. Thus, the excessive risk for DR3/4 individuals appears to depend on secondary interactions between DR and the environmental factors that trigger the onset of this disease and does not in itself indicate the existence of distinct susceptibility alleles in coupling with these genes, i.e., of genetic heterogeneity or overdominance.

Alleles↗
PubMed1986

Allele frequency distribution of two highly polymorphic DNA sequences in three ethnic groups and its application to the determination of paternity.

The allele frequency distribution of two highly polymorphic DNA sequences has been determined in three ethnic groups (American blacks, Caucasoids, and Hispanics) from the New York metropolitan area. The two loci examined were D14S1 and the flanking region of HRAS-1. The former was analyzed in EcoRI-digested DNA and the latter in TaqI-digested DNA. Approximately 700 DNA samples from unrelated individuals were digested with each of these enzymes and hybridized with the appropriate recombinant DNA probes. The size range of the DNA fragments detected for the D14S1 polymorphism varied from 14.3 to 32.5 kilobase pairs (kbp). The number of alleles identified under the experimental conditions used in this study was more than 40. For the HRAS-1 polymorphism, we have detected 18 different alleles varying in size from 1.85 to 4.5 kbp. Although the number of alleles observed in the different ethnic groups examined was very similar, the relative frequency of them varied significantly. The results presented here can be used as the basis for the utilization of DNA RFLP for the purpose of identity, such as paternity determinations or the analysis of forensic material. As an example, we have compared the results of paternity cases analyzed by HLA typing with those obtained with these two DNA polymorphisms. The values of paternity index and power of exclusion were similar by both procedures.

Alleles↗
PubMed1986

TCA: a polymorphic genetic marker in leukemias and melanoma cell lines.

TCA (T Cell system A) is a di-allelic system of HLA-like antigens encoded by genes located about 15 cM telomeric to HLA-A. In normal individuals, TCA antigens are only expressed on a subpopulation of T cells, the TG lymphocytes. We now report on the expression of TCA on leukemias and other malignancies. An increased proportion of cells carrying the TCA phenotype was encountered in testing peripheral blood lymphocytes from patients with acute lymphoblastic T-cell leukemia (T-ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). In contrast, patients with B-cell malignancies such as chronic lymphatic leukemia (CLL) and hairy cell leukemia (HCL) or non-T/non-B common acute lymphoblastic leukemia (common ALL) had normal proportions of TCA-positive lymphocytes. Quantitatively different levels of TCA expression are found on some melanoma cell lines and others are TCA negative. These variations are independent of the expression of HLA Class I antigens by the same cells. The expression of TCA antigens by malignant nonlymphoid cells suggests that this system may code for differentiation markers, important in the biology of neoplastic transformation.

Antigens, Neoplasm↗