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C M Zmijewski

Publications and source records attributed to C M Zmijewski.

At least 37 records · Page 2Linked to original sources
PubMed1989

Subtypes of HLA-DQ and -DR defined by DQB1 and DRB1 RFLPs: allele frequencies in the general population and in insulin-dependent diabetes (IDDM) and multiple sclerosis patients.

We have used the HLA-DQB1 gene as a Southern hybridization probe with TaqI-digested genomic DNA in a study of 600 haplotypes from unrelated individuals and have characterized HLA-DQB1 RFLP patterns associated with the DR specificities DR1-DRw10 and DN1. For six of the specificities (DR2, 4, w6, 7, w8 and 9), we have also identified subtypes (multiple DQB1 band patterns). In a previous study (Cox et al. 1988), we identified RFLPs and subtypes with a DRB1 probe. Using the present results from DQB1 RFLPs to supplement those from DRB1 RFLPs, it was possible to discriminate among all the DR specificities with the exception of a minority of DR7 and DR9 subtypes. A comparison of DQB1 and DRB1 subtypes in the same subjects showed strong linkage disequilibrium for subtypes of some but not all DR specificities. We have also determined the allele frequencies of the DQB1 subtypes in controls and in patients with insulin-dependent diabetes mellitus (IDDM) or multiple sclerosis (MS). A consideration of subtypes in patients and controls indicated that for most DR specificities, neither IDDM nor MS was more strongly associated with any of the DQB1 subtypes than with the serologically defined DR antigens. The exceptions were the DQB1 patterns corresponding to the DQw3.2 subtype of DR4 and the rarer subtype of DR2, which were found in higher frequency in IDDM patients, as has been previously reported.

Alleles↗
PubMed1988

Evaluation of B-cell immunity in patients with pretransplant sensitization.

The influence of presensitization (blood transfusions) on B-cell immunity as reflected in the serum of two groups of candidates for cadaveric donor renal allografts was examined. The first group initially had a high level of panel-reactive antibody (PRA) greater than 72% but experienced a large decrease in PRA (greater than 70%) 6-34 months prior to transplantation. In contrast, the second group maintained a high PRA (100%) for up to 28 months after sensitization and before transplantation. Three blood Three blood samples from each patient, representing a maximum time span of 34 months, were analyzed. Levels of IgG, IgM isohemagglutinins, and antitetanus antibody were used as indicators of B-cell function. There were no significant differences between the individual values of a single patient with regard to each parameter. However, Group II patients had elevated values of total IgG relative to Group I patients. Total serum IgG-subclass levels (IgG1, IgG2, IgG3, IgG4) were measured and the relationship between a specific IgG subclass and the PRA activity was determined. IgG1 values in Group II were higher than those found for Group I. The other IgG subclasses were all within normal levels and were not significantly different between Group I and Group II. When IgG-subclass typing of PRA was performed, IgG1 accounted for most of the activity in both groups and a fall in PRA-specific IgG1 was associated with the reduced PRA observed in Group I. The data indicate that humoral immunity, as reflected by total and specific immunoglobulin levels, is intact in general in the two groups of presensitized renal allograft candidates examined and that any loss of PRA activity reflects a reduction in a specific immune response.

B-Lymphocytes↗
PubMed1988

Analysis of DR and DQ gene products of the DR4 haplotype in patients with IDDM: possible involvement of more than one locus.

Fifteen DR4-bearing haplotypes from twelve patients with insulin-dependent diabetes mellitus (IDDM) were analyzed serologically, cellularly, and biochemically. The HLA-Dw composition of these DR4-positive haplotypes was Dw4 (46%), Dw14 (22%), and Dw10 (33%). The biochemical analysis by two-dimensional electrophoresis (2D-PAGE) of the DR beta chains showed that each Dw specificity is characterized by a specific DR4 beta chain that appears to be identical in normal and diabetic individuals. Analysis of DQ beta chains in the DR4-bearing haplotypes revealed that certain Dw specificities such as Dw4 are characterized by the presence of either the DQw7 (formerly DQw3.1) or DQw8 (formerly DQw3.2) alleles, which generate the Dw4.1 or Dw4.2 subtypes, respectively. Others such as Dw14 and Dw10 are characterized by the presence of the DQw8 allele. In our sample of 12 patients the Dw4.2 (Dw4, DR4 beta I-4 DQw8) and Dw10 (Dw10, DR4 beta I-1, DQw8) subtypes were predominant. It is concluded that individual DR beta and DQ beta gene products from the DR4-bearing haplotype of IDDM patients are identical to those of normal control subjects and that Dw14 as well as Dw10 are involved in disease susceptibility. We suggest that disease susceptibility may be influenced by more than one locus within the HLA-D region.

Diabetes Mellitus, Type 1↗
PubMed1988

Increased sharing of maternal HLA haplotypes among children exposed to diphenylhydantoin during pregnancy.

During investigation of HLA types among children exposed to diphenylhydantoin (DPH) in utero, we found no evidence of a distortion in haplotype sharing among affected sib pairs. Unexpectedly, however, we found a marked increase in the proportion of all sib pairs (not just affected ones) sharing maternal haplotypes. Among 14 two child families, 12 shared the maternal haplotype (expected would be seven); among families with more than two children the distortion was also pronounced. This finding, if verified in future studies, could indicate that something in the mothers, whether DPH use during pregnancy, or some genetic factor associated with seizures, or some effect of the seizures themselves, may be leading to non-random segregation of HLA haplotypes in their offspring.

Child↗
PubMed1988

HLA-DR typing "at the DNA level": RFLPs and subtypes detected with a DR beta cDNA probe.

The HLA-DR beta gene, used as a hybridization probe, detects RFLPs that correlate with HLA-DR specificities. Using genomic DNA from more than 200 individuals, we have carried out a population study with a cDNA probe for the DR beta chain, which, under appropriate conditions, does not cross-hybridize with genes from other HLA-D subregions (e.g., DP and DQ). We first assessed the correspondence between serologically defined HLA-DR types and DNA patterns obtained after digestion with TaqI and found that DNA patterns allowed us to identify most specificities. Only two pairs of antigens are not distinguishable: with the DR beta probe alone we cannot distinguish DR3 from DRw6 or DR7 from DRw9. However, the correct assignment can always be made for the first pair by hybridizing the same digests with a DQ alpha or DQ beta probe. Thus DR typing from the DNA patterns is practical and accurate. We also looked for serologically undetectable subtypes. RFLPs revealed high-frequency subtypes for the specificities DR 2, 3, 5, w6, 7, and w9. Some of these are more accurately viewed as variant haplotypes, since the relevant variation is probably not at the DR beta locus that determines the serological specificities but rather at other closely linked and highly homologous DR beta loci such as DR beta-III. Nevertheless, the existence of variant haplotypes for so many specificities indicates a wealth of polymorphic variation beyond that detected serologically and provides more specific markers for studies of various diseases associated with HLA-DR specificities.

Asian People↗
PubMed1987

Carbohydrate differences in HLA-DR molecules synthesized by alveolar macrophages and blood monocytes.

Two-dimensional gel electrophoresis was used to compare immunoprecipitated, radiolabeled HLA-DR molecules synthesized by alveolar macrophages (AM) and blood monocytes (BM) of the same healthy, nonsmoking volunteers. No charge differences were noted by isoelectric focusing. Molecular weight analysis of HLA-DR from AM revealed a complex pattern of radioactive spots differing slightly in molecular weight. This pattern was apparent in both the alpha and the beta chains. In contrast, a simpler pattern without the slight molecular weight differences was noted in HLA-DR from BM. The differences were eliminated by labeling AM and BM in the presence of tunicamycin, a specific inhibitor of protein-carbohydrate linkages of the N-glycosidic type. Thus, it appears that neutral, N-linked carbohydrate moieties account for the differences in HLA-DR molecules between AM and BM. The differential glycosylation of HLA-DR molecules in AM and BM may relate to mononuclear phagocyte development as well as antigen-presenting function.

Carbohydrate Metabolism↗
PubMed1986

Cell surface antigen identification by a modified fluorescein immunosphere method.

Fluorescein immunospheres may be used in an indirect technic to label lymphocyte cell surface antigens. Wright's counter-staining allows simultaneous identification of fine morphology and surface antigen properties. Studies designed to determine methods for separating cells with bound immunospheres from free immunospheres revealed that removal of unbound immunospheres by flotation over cold protein solution creates excessive numbers of false negatives. Glutaraldehyde cross-linking of the primary and secondary antibodies linking immunospheres to the lymphocyte stabilizes the complex. This modification of the fluorescein immunosphere method compares favorably with flow cytometry.

Adult↗
PubMed1984

Mixed lymphocyte reactivity in cats.

A method was developed to perform primary one-way mixed lymphocyte cultures (MLC) with cat cells. A polymorphic system of MLC reactivities was found within a cat population. In family studies, alloreactivity segregated as a single genetic locus with codominantly expressed products, designated feline lymphocyte defined (Fld)--although closely linked multigene control remains possible. The relationship of Fld to a putative feline major histocompatibility complex is discussed.

Animals↗
PubMed1984

Improved T cell subset monitoring by immunogold staining following renal transplantation.

Enumeration of peripheral blood T cells, functional T cell subsets, and B cells by immunogold staining (IGS) was compared with analysis by flow cytometry in 52 renal allograft recipients. Results by the IGS method compared favorably with those obtained by flow analysis. IGS is a simple, inexpensive technique that is readily adaptable to the setting of posttransplant immune monitoring.

Antigens, Surface↗
PubMed1984

HLA-DR histocompatibility leukocyte antigens permit cultured human melanoma cells from early but not advanced disease to stimulate autologous lymphocytes.

HLA-DR histocompatibility antigens are commonly expressed by the melanocytes of melanoma and its precursors, but not by the melanocyte of normal skin. Further, the primary lesion of biologically early melanoma is commonly infiltrated with host T cells. Advanced disease is characterized by a paucity of such cells. To investigate the interaction of melanoma cells and autologous lymphocytes and its dependence on HLA-DR expression, we have established cell lines from biologically early (4 lines) and advanced disease (11 lines) and examined their capacity to stimulate blastogenesis of autologous T cells in vitro. Melanocytes from early disease expressed HLA-DR antigens and stimulated autologous T cells. Those from advanced disease, irrespective of DR expression, were nonstimulatory. To determine whether expression of DR was required for melanoma cells to be stimulatory, we first treated a stimulating cell line of DR3 allospecificity with anti-DR3-specific serum and demonstrated marked inhibition of its capacity to provoke blastogenesis. Next we used fluorescence-activated flow cytometry to sort a stimulating line heterogeneous for DR expression into DR-enriched and -depleted populations. When such cells were examined in the lymphocyte proliferation assay, their stimulatory capacity was proportional to their quantitative expression of HLA-DR. These studies indicate that cell lines may reflect important biological differences between early and advanced melanoma. HLA-DR expression may be an early event in neoplasia of melanocytes. These antigens are able to interact directly with autologous T cells; and their expression is necessary, but not sufficient, for melanoma cells to induce lymphocyte proliferation.

Antilymphocyte Serum↗
PubMed1984

HLA and disease.

This review describes the greater portion of a large number of new studies on HLA and disease association which has appeared in the literature since 1979. The majority of these are concerned with the association of certain diseases with class II major histocompatibility complex antigens. The possible biologic significance of these associations in terms of their probable etiology appears to be the prevailing theme. Current thinking regarding certain heritable diseases is described. It seems that although much has been done to resolve the genetics of insulin-dependent diabetes mellitus, other diseases such a multiple sclerosis still remain a mystery. Doubtlessly, much will be gained from DNA cloning and sequencing studies proposed for the future. A great deal of new information has been obtained relative to HLA itself. New loci have been postulated in the HLA-D/DR region through the use of powerful immunochemical procedures made possibly by the advent of modern technological advances. The impact of these developments on our understanding of the function of the MHC in man and its possible relationship to disease are discussed.

Animals↗
PubMed1983

Segregation of HLA in families with oral clefts: evidence against linkage between isolated cleft palate and HLA.

In an earlier study of families with two or more sibs affected with a cleft of the lip with or without clefts of the palate, we found no evidence for close linkage of HLA with this malformation. In the present study, we confine our attention to isolated cleft palate, an entity that is genetically distinct from cleft palate associated with cleft lip. In 15 sibships with two or more affected sibs, cleft palate, and parental HLA haplotypes assorted independently in the affected sibs, providing evidence against close linkage of this phenotype.

Adult↗
PubMed1981

Monoclonal rat anti-MHC alloantibodies detect HLA-linked polymorphisms in humans.

Two monoclonal rat anti-MHC alloantibodies detect a polymorphic determinant expressed on the peripheral lymphocytes of normal human donors. The pattern of cytotoxicity observed with these antibodies correlated with the HLA type of the individual; no HLA-A-locus specificities showed significant associations, and all of the HLA-B-locus specificities showing significant association were members of the Bw6 supertype. Family studies established that the determinant detected by the monoclonal antibodies is linked to HLA. These studies therefore provide an alternative basis for the production of monoclonal antibodies to polymorphic HLA determinants based on the conservation of polymorphic MHC determinants between man and rats.

Animals↗