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Biomedical subjects

J Klein

Publications and source records attributed to J Klein.

At least 649 records · Page 36Linked to original sources
PubMed1987

Comparative multicentre study of the immunogenicity of different hepatitis B vaccines in healthy volunteers.

In a comparative study of the immunogenicity of different hepatitis B vaccines, 339 healthy seronegative adults at three different centres were randomly allocated to receive either three doses of a yeast-derived vaccine at one of three different dose levels (10, 20, or 40 micrograms; SmithKline Biologicals) or one of two commercial plasma-derived vaccines at standard dose levels (5 micrograms, Institut Pasteur Production or 20 micrograms, Merck Sharp & Dohme). The subjects were inoculated intramuscularly in the deltoid region according to a 0, 1, and 6 month schedule. No severe or serious adverse reactions attributed to any of the vaccines were observed. One month after the third vaccine dose, seroconversion rates ranged from 95% to 100% in all groups with only 6 subjects failing to seroconvert. Although there were no statistically significant intra-centre differences in antibody levels, the Tours/Chateauroux groups generally attained higher antibody levels than those from Limoges for the same yeast-derived vaccine dose. This unexplained difference between centres was not found for the plasma-derived vaccines. Older subjects responded less well than younger ones and females attained higher antibody levels than did males. The yeast-derived vaccine is comparable to the two commercially available plasma-derived vaccines in terms of reactogenicity and immunogenicity.

Adult↗
PubMed1986

Human genetic defect in leukotriene C4 synthesis.

Normal human platelets metabolise [3H]-LTA4 into [3H]-LTC4. Platelets from patients with glutathione synthetase deficiency possessing 10-30% of normal levels of cellular glutathione showed marked reduction in capacity to form [3H]-LTC4 (8-10% of normal) even though exogenous reduced glutathione was added to the incubation medium. To our knowledge this is the first demonstration of a genetic defect in LTC4 synthetase coupled to a defect in cellular glutathione levels.

Arachidonic Acids↗
PubMed1986

Two adjacent epitopes on a synthetic dodecapeptide induce lactate dehydrogenase B-specific helper and suppressor T cells.

The outcome of an immune response to the enzyme lactate dehydrogenase B (LDH-B) is determined by the interplay between two types of regulatory T lymphocytes, T helper (Th) and T suppressor (Ts) cells. Most mouse strains are capable of generating Th but not Ts cells, and are therefore high responders to LDH-B in terms of both antibody production and antigen-specific T-cell proliferation. However, in strains expressing the b or k allele at the E beta locus of the major histocompatibility complex (Mhc), Ts cells are induced that partly or totally abrogate the proliferative response of Th cells to LDH-B. As a result, these strains are phenotypically medium (E beta b expressors) or low (E beta k expressors) responders. Because the suppression in the LDH-B system is antigen-specific (i.e. it only affects LDH-B-specific Th cells), it is conceivable that the Th and Ts cells use the antigen itself to communicate with each other. To investigate this possibility, we set out to determine which epitopes of the LDH-B molecule are recognized by Th and Ts cells. On the basis of previous studies, a loop structure extending from residue 211 to residue 224 of pig LDH-B appeared to be preferentially recognized by most Th-type (class II Mhc-restricted, proliferating) clones. By using a synthetic peptide, we demonstrate here that both Th and Ts cells are induced by the 211-222 stretch of LDH-B sequence. The use of two further dodecapeptides, each with a single amino-acid substitution in comparison with the pig 211-222 sequence, has revealed that Th and Ts cells have different fine specificities. Thus the loop appears to have two closely linked, if not overlapping, epitopes, one recognized by Th and the other by Ts cells. This finding is consistent with two possible mechanisms of suppression, namely bridging of Th and Ts cells by antigen and subsequent transmission of a suppressive signal, and competition for antigen between Th and Ts cells.

Animals↗
PubMed1986

Metabolism of leukotriene A4 into C4 by human platelets.

Tritium-labelled leukotriene A4 is converted by a suspension of human platelets into leukotriene C4. The conversion is stimulated by reduced glutathione and is dependent on the platelet concentration. Formation of leukotriene C4 is temperature and time dependent and is destroyed by heating the platelets at 100 degrees C for 5 min. Verification of leukotriene C4 formation was obtained by conversion into leukotriene D4 during reaction of the HPLC-purified platelet-derived leukotriene C4 with commercial gamma-glutamyl transpeptidase. In separate experiments we incubated authentic tritiated leukotriene C4 with human platelets and we showed the formation of tritiated leukotriene D4, demonstrating the presence of gamma-glutamyl transpeptidase activity in these cells. This activity could be blocked by the presence of reduced glutathione in the incubation mixture. In contrast, erythrocytes converted tritiated leukotriene A4 almost exclusively into leukotriene B4. Although platelets have been reported to lack 5-lipoxygenase activity, our study demonstrates that platelets possess the necessary machinery to transform leukotriene A4 into leukotrienes C4 and D4. Our results suggest that an intracellular interaction between platelets and leukotriene A4-forming cells, e.g., polymorphonuclear leukocytes, could lead to the formation of these potent peptidolipids in the circulation.

Arachidonate Lipoxygenases↗
PubMed1986

Epoxide hydratase assay in human platelets using hepoxilin A3 as a lipid substrate.

1-14C-labelled hepoxilin A3 (8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid) was generated from 1-14C-labelled arachidonic acid during incubation with a rat lung preparation lacking epoxide hydratase activity. The HPLC purified hepoxilin A3 gave only two isomeric 8,11,12-triols (termed trioxilins A3) upon incubation with a rat lung preparation containing epoxide hydratase activity. Based on this simple reaction an assay was developed using only 2000 cpm/tube of substrate and aliquots of a homogenate of platelet membranes from man. Products were assayed by thin-layer radiochromatography. Males were noted to have higher epoxide hydratase activity for this substrate than females.

8,11,14-Eicosatrienoic Acid↗
PubMed1986

Antigen presentation by liposomes: inhibition with antibodies.

The involvement of both antigen and class II major histocompatibility complex (MHC) molecules in T cell activation by liposome-bound antigens was investigated. We used a pigeon cytochrome c (PCC)-specific Ek-restricted T cell hybridoma that can be activated to produce interleukin 2 by liposomes carrying either PCC and Ek molecules, or a high concentration of PCC alone. We demonstrated that the MHC-restricted response of this hybridoma to liposomes is specifically blocked by both anti-MHC and anti-PCC monoclonal antibodies, whereas unrestricted activation is only inhibited by PCC-specific antibody.

Animals↗
PubMed1986

An attempt to produce "pre-T" cell hybridomas and to identify their antigens.

With the aim of identifying some of the stages in the development of pre-T cells (cells of the T cell lineage before they enter the thymus), we have produced a large number of hybridomas by the fusion of BALB/c bone marrow cells, bone marrow cells from BALB/c-nu/nu mice, BALB/c fetal liver cells and BALB/c fetal thymocytes with the AKR thymoma BW5147. The hybridomas were selected for the expression of the Thy-1.2 antigen of the normal cell donor and for their ability to produce interleukin 2 (IL 2) upon co-culture with irradiated normal spleen cells. A set of these hybridomas is described in this communication. The hybridomas were then used to immunize rats and to generate monoclonal antibody-producing B cell hybridomas. Most, if not all, of the immunizing hybridomas were derived from pre-T cells as evidenced by the fact that they produce IL 2, and express some of the T cell markers (the Thy-1.2, Ly-1, Ly-2 or L3T4 antigens). The monoclonal antibodies were tested on a panel of pre-T cell hybridomas and on normal cells obtained from spleen, lymph nodes, thymus and bone marrow. The testing was carried out by the microcytotoxicity assay and flow cytometric analysis. Three groups of antibodies could be distinguished. Some antibodies were broadly reactive, being positive with virtually all the clones in the pre-T cell panel and with a substantial fraction of normal lymphoid cells. The identity of the antigens detected by these antibodies remains unknown but they do not seem to correspond to any of the known cell surface markers. Other antibodies reacted only with some of the pre-T cell clones and did not react at all with normal lymphoid cells obtained from adult animals. Finally, other antibodies still reacted only with a minor subpopulation of thymocytes or of thymocytes and bone marrow cells, as well as some of the pre-T cell clones; they did not react with spleen and lymph node cells. These antibodies might be specific for cells in the prethymic phase of the T cell differentiation pathway. They should prove useful for the identification of pre-T cell markers and hence for the isolation of pre-T cells and their functional analysis.

Animals↗
PubMed1986

Low H-2 polymorphism in some Israeli wild mouse populations.

Two populations of the wild house mouse, Mus domesticus, found living close to each other (one inhabited a chicken coop and the other an open field at the Educational Farm of the Hebrew University of Jerusalem, East Talpiot, Jerusalem) were studied for their H-2 polymorphism. These two populations were selected because they are well characterized in terms of their ecological parameters; they have been under continuous surveillance for several years. Twenty-seven H-2 homozygous lines were produced by mating wild mice from these two populations with laboratory strains. The H-2w homozygotes were then characterized by serological typing with monoclonal and polyclonal antibodies specific for the known allomorphs controlled by the class I H-2K and H-2D loci or the class II H-2A and H-2E loci. They were also used as donors for immunizations and for the selection of antisera defining the H-2 haplotypes carried by these lines. Four new H-2 haplotypes could be identified: H-2w82 (Kw16 Dw82), H-2w83 (Kw83 Dw16), H-2w84 (Kw84 Dw84), and H-2w85 (Kw83 Dw84), the last haplotype being a recombinant derived from H-2w83 and H-2w84. Antisera defining the new haplotypes were then used for a study of the wild populations. This study revealed that the populations contain only the four identified H-2 haplotypes, having three alleles at the H-2K locus (Kw16, Kw83, Kw84) and three alleles at the H-2D locus (Dw16, Dw82, and Dw84). The alleles occur in the populations with a frequency of 0.12-0.54. There were no significant differences in gene frequencies between the two populations, and the allele frequencies remained more or less stable. There was a significant excess of heterozygotes for at least some of the genes, compared with the frequency expected from Hardy-Weinberg equilibrium. The same antisera were also used to type other populations in the vicinity of Jerusalem. In one population, located 30 km west of Jerusalem, the mice failed to react with any of the reagents. In the other two populations, located 15 km west and 40 km northeast of Jerusalem, three of the four H-2 haplotypes found in East Talpiot were present at high frequencies. It appears, therefore, that only three main H-2 haplotypes and two or three minor ones are present in the area around Jerusalem. This study thus provides the first example of a large mainland population in which the H-2 polymorphism is comparable to that of many other non-H-2 loci.

Alleles↗