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F C Grumet

Publications and source records attributed to F C Grumet.

At least 91 records · Page 5Linked to original sources
PubMed1982

ST-16: a new Bw16 subtype present in Mexican-Americans.

Using a large battery of Bw16, w38, and w39 antisera, a new variant of Bw16 has been identified in four unrelated Mexican-American families. The serologic pattern obtained is distinct from that for Bw38, Bw39, and 8W57 antigens. Absorption studies confirm the existence of this new Bw16 subtype which we term ST-16. ST-16 is Bw6-associated, with antigen frequency estimated to be 2.5% in Mexican-Americans.

Absorption↗
PubMed1982

Production of functional human T-T hybridomas in selection medium lacking aminopterin and thymidine.

The production of hybridomas between immunologically activated T cells and malignant T-cell lines offers a potentially unlimited source of soluble T-cell-derived products. Recently, human T-T hybrids have been described; however, their use has been hampered by slow growth and chromosomal instability due at least in part to the presence of thymidine in the traditional hypoxanthine/aminopterin/thymidine (HAT) selection medium. In this report, we describe the development of a rapidly growing hypoxanthine phosphoribosyltransferase-deficient human T-cell line designated J3R7, the use of azaserine/hypoxanthine (AH) medium as an alternative selection medium to HAT medium, and the production of functional T-T hybrids by using the J3R7 line and the AH selection technique. Hybrids selected in AH medium were 4-fold greater in number and 3-fold faster in growth rate than hybrids grown in HAT medium. No stable clones were obtained from HAT cultures whereas AH-derived hybrids could be readily cloned by the method of limiting dilution. Evidence for hybridization included (i) the presence of approximately twice the number of chromosomes in hybrids than in J3R7 cells; (ii) the presence on hybrid cells of the Leu-3a surface antigen, present on normal helper T cells but not on J3R7 cells; (iii) the expression of HLA antigens of both the normal T-cell partner and the J3R7 line; and (iv) the constitutive secretion of interleukin 2 from multiple hybrid clones but not from the J3R7 cell line. Thus far, these clones have maintained their rapid growth, chromosome number, surface phenotype, and constitutive secretion of interleukin 2 for 4 months.

Aminopterin↗
PubMed1982

Protein A binding assay for the identification of HLA antigens on peripheral blood lymphocytes by monoclonal antibodies: application to HLA B27.

Splenocytes from mice immunized with purified, papain-solubilized HLA B27 antigen and/or human lymphocytes bearing the B27 specificity were fused with myeloma cell lines NSI or Sp2. The screening strategy employed a protein A binding assay in which various target cells were used. First, the hybrid cell supernatants were screened against B lymphocyte cell lines of known HLA specificities and the Daudi cell line, which does not express HLA-A, B, or C antigens. Second, a panel of PBLs were used as target cells. It was necessary to refine the protein A binding assay by preabsorbing the radiolabeled protein A with PBLs and by precoating the test wells with ovalbumin. Clones selected by these criteria were further tested by indirect immunoprecipitation and by inhibition of binding or microcytotoxicty to target call lines with purified HLA antigens or beta 2m. Forty-four clones were selected which showed varying degrees of specificity for allo- and nonallo-specific determinants and one clone was selected which was specific for beta 2m. Clone 27M1 which was previously shown to be specific or HLA-B27 as judged by conventional microcytotoxicity testing (Grumet et al., Lancet No. 8239, II:174, 1981) was compared with other clones using the above parameters for evaluation. Antibody from clone 27M1 showed preferential binding to B27 positive cell lines and PBLs, lesser binding to B7 positive target cells, and no binding to B40 positive target cells. Purified B27 antigen (papain) from two sources including the B27 target cell line, was able to inhibit the binding of antibodies from 27M1 to target cells. The extension of the protein A binding assay to PBLs has made it possible to more accurately quantitate the binding or inhibition of binding of antibodies to panels of PBLs.

Animals↗
PubMed1982

Mechanism of enhanced complement-dependent cytotoxicity of papain-treated lymphocytes: evidence for increased stability of classical pathway C3 convertase.

The mechanisms of enhanced antibody-mediated, complement-dependent cytotoxicity caused by proteolytic treatment of cells was studied in a model system based on HLA microlymphocytotoxicity methods. In this model, papain treatment of lymphocytes resulted in a) no change in antibody binding, b) a slight decrease in initial binding of C4, c) a marked increase in stability of cell-bound C4b, resulting in d) an increase of cell-bound C3, and e) no increase in lytic efficiency of the C5b-9 membrane attack complex. We conclude that the most important step in papain enhancement of lysis of lymphocytes is an increased stability of cell-bound C4b, possibly through decreased surface binding of C4-bp. This mechanism may be relevant to the pathologically increased lysis of cells occurring in patients with hereditary erythroblastic multinuclearity with a positive acidified-serum test (HEM-PAS).

Anemia, Dyserythropoietic, Congenital↗
PubMed1981

Strong linkage disequilibria among HLA-Bw50, BfS1, and HLA-DR3/DR7, and mapping of the Bf locus.

Based on genotypic and phenotypic studies we have found strong linkage disequilibria in Caucasians among the genes HLA-Bw50, BfS1, and HLA-DR3 and/or -DR7. The relative disequilibria, which are among the highest described in man, are delta r (BfS1, DR7) = 0.51, delta r (Bw50, BfS1, DR7) = 0.36, delta r (Bw50, DR3 or 7) = 0.72, delta r (BfS1, DR3 or 7) = 0.91, delta r (Bw50, BfS1, DR3 or 7) = 0.73. The previously described high delta r (Bw50, BfS1) and delta r (Bw50, DR7) have also been confirmed. A B parallel DR crossover family is also presented that, together with previously reported recombinant families, confirms that the Bf locus resides between HLA-B and HLA-DR. These data suggest the existence of a supergene complex of Bw50, BfS1, DR3/7 (or MB2), and hypotheses to account for the observed disequilibria are discussed.

Chromosome Mapping↗
PubMed1981

Prevention of transfusion-acquired cytomegalovirus infections in newborn infants.

Transfusion-acquired cytomegalovirus infections occurred in 13.5% of 74 infants of seronegative mothers who were exposed to one or more blood donors who had a CMV indirect hemagglutination titer of 1:8 or higher. None of 90 infants of seronegative mothers exposed only to donors with CMV IHA titers of less than 1:8 became infected. Ten of 41 (24%) infants of seronegative mothers who received more than 50 ml of packed red blood cells and who were exposed to at least one seropositive donor became infected. None of 23 infants of seronegative mothers who received this amount of blood but who were exposed only to seronegative donors became infected. Fatal or serious symptoms developed in 50% of the infected infants of seronegative mothers and in none of the 32 infected infants of seropositive mothers. Acquired CMV infections occurred in 15% of infants of seropositive mothers who were exposed to the red blood cells of seropositive donors and in 17.6% of infants of seropositive mothers exposed only to seronegative donors. Use of seronegative donors reduced the prevalence of excretion of CMV among hospitalized infants who were 4 weeks of age or older from 12.5 to 1.8% and eliminated acquired CMV infections in infants of seronegative mothers.

Antibodies, Viral↗
PubMed1981

Activation of human T lymphocyte subsets: helper and suppressor/cytotoxic T cells recognize and respond to distinct histocompatibility antigens.

This study was directed at determining the major histocompatibility complex (MHC) antigens recognized by helper (Leu-3) and suppressor-cytotoxic (Leu-2) T lymphocyte subsets in man. These 2 subsets were isolated from peripheral blood with monoclonal antibodies and challenged in vitro with various stimuli. Only Leu-3 cells proliferated in response to autologous nonrosetting cells and soluble antigens, suggesting that helper but not suppressor-cytotoxic T cells recognize autologous HLA-DR antigen. Furthermore, only Leu-3 T cells responded to allogeneic DR antigen; this was shown in reactions between 2 siblings who were HLA-identical except for a single disparity at HLA-DR caused by a crossover event. Leu-3 cells activated in primary allogeneic mixed leukocyte reactions (MLR) responded equally in secondary allogeneic MLR to the priming cells and to cells that were identical at HLA-DR but discordant at HLA-A, B, and C to the priming cell. The antigens responsible for stimulating Leu-2 cells in allogeneic MLR were not identified, although the results are compatible with a role for HLA-A and B antigens and exclude a dominant role for HLA-DR. These data indicate that the helper and suppressor-cytotoxic T cell subsets in man respond differentially to MHC antigens in a manner analogous to the murine Lyt-2- 3- and Lyt-2+ 3+ populations.

Antibodies, Monoclonal↗
PubMed1980

Linkage disequilibria between HLA-B and the rarer properdin factor B alleles, BfF1 and BfS1.

Phenotypic association and highly significant linkage disequilibria have been demonstrated for HLA-B18 and BfF1 and HLA-Bw50 and BfS1 alleles among Caucasians from Australia and the United States (San Francisco Bay area). The HLA-B18, BfF1 association appears to be associated with HLA-Aw30. It is possible that BfS1 arose as a mutation, after the evolutionary splitting of HLA-Bw21, on an HLA-Bw50 haplotype, and that BfF1 arose on an HLA-Aw30, B18 haplotype.

Alleles↗
PubMed1980

A new micromethod for the in vitro detection of antiplatelet antibodies: C-FDA thrombocytotoxicity.

A new microtechnique, C-FDA, for the in vitro detection of antiplatelet antibodies, is described. This technique is faster and simpler than either 51Cr thrombocytotoxicity or immunofluorescence (IF). C-FDA is more sensitive than 51Cr for all (anti-HLA, --P1A1, ABO, drug-related, and ITP-related) antibodies tested. Although IF was more sensitive for many types of antibodies, C-FDA was as good or better a clinical test method for all drug-related and isoimmune neonatal thrombocytopenia patient sera tested. Preliminary data also suggest that this method detects possible new non-HLA, non-ABO, nonP1A1 platelet antigens.

ABO Blood-Group System↗
PubMed1980

New transfusion program for an intensive care nursery.

We have established a new transfusion program for an intensive care nursery which is based on crossmatching several infants to the same unit of type O Rh0(D) negative packed red blood cells, dividing the unit into quadpacks, and allowing multiple entry into each quadpack over a 24-hour period in the nursery. With this procedure, each donor unit can be used to provide multiple transfusions to four infants over a four-day period. Follow-up of transfusion recipients revealed that 20% had evidence of previous or ongoing CMB infection at 10 months of age, a prevalence comparable to that for transfused infants in other studies. We found no evidence for transmission of HB infection and a low risk of allosensitization to red cell and lymphocyte antigens.

Blood Transfusion↗
PubMed1980

HLA-DR epitope region definition by use of monoclonal antibody probes.

Definition of HLA-DR epitopes has been attempted by utilizing monoclonal antibody probes. Hybridoma antibodies L203 and L227, known to bind different epitopes on human Ia-like molecules, were tested for their ability to block cytotoxicity of monoclonal and allogeneic anti-DR antibodies. Monoclonal cytotoxic antibodies segregated into two groups: those more effectively blocked by L203, and those more effectively blocked by L227. Alloantisera also segregated into two groups, but according to their DR specificity. Anti-DR1, -2, and -3 alloantisera were effectively blocked by both L203 and L227, whereas anti-DR7, -w9, -w10, and MT1 alloantisera were not blocked by either. Blocking was not correlated with immunoglobulin class of the alloantibody and further definition of the mechanism of cytotoxicity blocking remains to be elucidated. Based on these data and prior binding and immunochemical studies with L203 and L227, a model is proposed in which the tertiary structure of each DR molecule, or complex of associated molecules on the cell surface, has two reference epitopes, one defined by L203, and another defined by L227. HLA-DR epitopes defined by the cytotoxic monoclonal or alloantibodies to the L203 or L227 epitope in order to begin epitope mapping or grouping.

Animals↗