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Biomedical subjects

C M Zmijewski

Publications and source records attributed to C M Zmijewski.

At least 55 records · Page 3Linked to original sources
PubMed1980

Monoclonal rat anti-major histocompatibility complex antibodies display specificity for rat, mouse, and human target cells.

24 monoclonal rat antibodies are described that are reactive with determinants encoded by the major histocompatibility complex (MHC) of the rat. These hybridoma antibodies were derived by fusing mutant mouse myeloma cells to spleen cells from Lewis rats immunized with allogeneic Brown Norway cells. All 24 antibodies are cytotoxic for both Brown Norway target cells and target cells from the appropriate MHC congenic rats. Pattern of cytotoxicity and hemagglutination strongly suggest reactivity against class I (K or D equivalent) rat MHC determinants. Cytotoxic cross-reactivity patterns were generated for each monoclonal antibody on a panel of rat and mouse lymphoid cells and human peripheral T lymphocytes. A high degree of interspecies cross-reactivity was noted with approximately one-half of the antibodies positive on human and/or mouse target cells. 11 antibodies recognized polymorphic determinants in the mouse, and, by using target cells from MHC congenic mouse strains, it was shown that these determinants are encoded by genes within the H-2 complex. Finally, by considering the overall reactivity patterns of these monclonal antibodies on all target cells, one can show that these 24 antibodies represent a minimum of 14 antibody specificities.

Animals↗
PubMed1980

Gene dosage and suceptibility to insulin-dependent diabetes.

1. All members of 33 families in which two or more sibs have insulin-dependent diabetes mellitus (IDDM) were HLA-typed. The results strongly support the hypothesis that, closely linked to the HLA region, there is a locus (S) for susceptibility to IDDM. We use Sd for alleles at this locus which confer susceptibility to disease, and Sa for all other alleles. 2. Published prevalence (recurrence) rates for relatives of an IDDM proband, which are essential for the analysis, are reviewed critically, and a new estimate of prevalence at age 30 in the general population is calculated from published data. 3. The analysis allows for greater risk (penetrance) of the genotype SdSd (two doses of Sd) than of SaSd (one dose of Sd) and for recombination between the HLA region and S. With either our own data on 26 affected sib pairs or a much larger sample assembled by pooling with published data, the maximum-likelihood estimate of the two-dose penetrance is 71%, of the one dose penetrance 6.5%. The hypothesis of differential penetrance according to gene dosage provides a significantly better explanation than either simple dominant or simple recessive inheritance. 4. Estimates of the recombination fraction between HLA and S are very sensitive to the proportion of affected sib pairs sharing neither HLA haplotype, which varies considerably among the samples pooled. With the pooled data the recombination fraction is estimated as 3%, but in view of the strong associations with particular HLA alleles seen in population data, this should probably be considered an upper limit.

Adolescent↗
PubMed1980

Segregation of HLA in sibs with cleft lip or cleft lip and palate: evidence against genetic linkage.

The segregation of HLA haplotypes (A, B, and C loci) was studied in eight families in which two sibs were affected with cleft lip or cleft lip and palate. HLA typing was performed in parents and sibs and in specific cases, other family members. Segregation of HLA haplotypes did not differ significantly from random Mendelian expectation. Three of the eight affected sib pairs differed in both HLA haplotypes, which is not expected if there is close linkage with susceptibility to clefting. Thus, it is very unlikely that spontaneous cleft lip or cleft lip and palate is closely linked to HLA.

Chromosome Mapping↗
PubMed1979

Inheritance of susceptibility to juvenile onset diabetes.

Regardless of the well-documented population associations between juvenile-onset diabetes (JOD) and certain HLA types, whatever haplotypes are segregating in JOD families may be followed to provide information on mode of inheritance of the disorder. It is essential to group together for analysis families with the same number of affected sibs. We assume a single locus determining susceptibility, closely linked to the HLA region, and ignore recombination, expected to be rare. Our first approach also assumes that the frequency of the susceptible genotype is so small that affected individuals may be considered to arise from only one mating type; the particular mating type depends on the mode of inheritance of susceptibility. Our sample is the result of pooling our own data with published studies of HLA haplotype segregation in families with two or more JOD offspring. Given the assumptions, we find that the data are more plausibly explained by a one-dose than by a two-dose or "recessive" hypothesis. We then develop the analysis further by adding a crude but explicit estimate of the frequency of the susceptible genotype, based on disease prevalence and penetrance of the genotype. The one-dose hypothesis is strongly supported by this analysis as well. We also consider some problems of ascertainment arising from heterogeneity of the disorder and selection against diabetics. Studies involving unaffected relatives of diabetics are suggested which might test further the conclusions drawn here.

Alleles↗
PubMed1978

Expression of HLA-A, but not of HLA-B, in mouse-human somatic cell hybrids carrying the region p21 leads to pter of human chromosome 6.

Mouse-human somatic cell hybrids containing human chromosome 17 carrying the region p21 leads to pter of human chromosome 6 and no other human chromosomes, were found to express HLA-A but not HLA-B. Counterselection of the hybrid cells in medium containing 5-bromodeoxyuridine resulted in the growth of hybrid cells that have concordantly lost the expression of HLA-A and the human translocation chromosome.

Animals↗
PubMed1978

Spontaneous cell-mediated cytotoxicity in humans. Distribution and characterization of the effector cell.

When lymphocytes from healthy donors were tested as effector cells, the cytotoxic activities observed in spontaneous and in antibody-dependent cell-mediated cytotoxicity were positively correlated. However, with lymphocyte preparations obtained from renal patients, a dissociation between the two activities was occasionally observed. Human natural killer cells are lymphocytes, with receptors for the Fc fragment of IgG molecules, but with no surface immunoglobulin. Their cytotoxicity is reduced by the presence of granulocytes or monocytes. After separation of rosetting and non-rosetting cells with AET- (2-aminoethylisothiouronium bromide hydrobromide) or neuraminidase-treated sheep erythrocytes, the majority of the activity was recovered in the non-rosetting fraction, but a portion of it was present consistently in the rosetting cell fraction. Cells in the latter fraction also displayed receptors for the Fc fragment of immunoglobulin G.

Adult↗
PubMed1976

Transfusion reaction with pulmonary infiltration associated with HL-A-specific leukocyte antibodies.

A case of a non-hemolytic transfusion reaction with pulmonary infiltration secondary to leukocyte antibodies is described, and previously reported cases are reviewed. This type of reaction can be diagnosed at the bedside when a patient develops fever, hypotension and dyspnea within a few hours following transfusion of whole blood or a plasma product. The roentgenogram of the chest shows pulmonary infiltrates with a normal cardiac silhouette constituting non-cardiac pulmonary edema. To provide laboratory confirmation of this reaction, it is essential to search for leukocyte antibodies by both leukoagglutinin and cytotoxic technics, as well as to determine HL-A phenotypes of both donor and recipient. As the plasma products involved usually come from multiparous women, donor parity should be a routine question in the donor interview in transfusion services. To prevent this reaction, which may prove fatal, blood donated by women who have two or more children should be used for packed cells only.

Adult↗
PubMed1976

HLA-related control of spontaneous and antibody-dependent cell-mediated cytotoxic activity in humans.

Normal human lymphocyte preparations were tested for their ability to lyse both antibody-coated and unsensitized human target cell lines. The capacity to induce these two types of cell-mediated cytotoxicity, antibody-dependent (Ab-CMC) and spontaneous (Sp-CMC), was detected by a 51Cr release assay. The reactivity of lymphocytes from 1. individual donors showed a positive and highly significanlty correlation between Ab-CMC and Sp-CMC, leading to the hypothesis that the same type of effector cell is involved in the two cytotoxic mechanisms. Lymphocytes from male donors were about twice as effective as those from female donors in both systems. Moreover, the effector cells from male donors carrying HLA antigens A3 and B7 displayed a significantly lower reactivity in both Sp-CMC and Ab-CMC when compared with lymphocytes from male donors bearing any other HLA haplotype. The possible significance of the hyporeactivity of lymphocytes from normal subjects with HLA-A3,B7 haplotype in relation to an increased susceptibility to multiple sclerosis (MS) is discussed.

Adult↗
PubMed1970

Soluble HL-A7 antigen: localization in the beta-lipoprotein fraction of human serum.

The HL-A7 antigen of human leukocytes occurs as a soluble, low-density lipoprotein in the serum of HL-A7-positive individuals. Its presence in high concentration may inhibit direct leukocyte grouping, leading to erroneous results. This finding affords an easy method for the preparation of monospecific cytotoxic antiserums by absorption with serum fractions rather than leukocytes.

Antigens↗