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J Borst

Publications and source records attributed to J Borst.

At least 109 records · Page 6Linked to original sources
PubMed1984

HLA-DC antigens can serve as recognition elements for human cytotoxic T lymphocytes.

The specificity of four cytotoxic T lymphocyte (CTL) clones which recognize class II major histocompatibility complex (MHC) antigens was analyzed. All clones recognized antigens associated with the serologically defined HLA-DRw6 specificity. The activity of two of these clones, JR-2-2 and JR-2-10, could be inhibited by a monoclonal antibody Q 5/13 specific for a monomorphic determinant present on HLA-DR. In contrast, the activity of the two other CTL clones, JR-2-19 and JR-2-26, was not blocked by Q 5/13, but by a new monoclonal reagent, SPV-L3. This latter monoclonal antibody precipitated a two-chain structure of 28 kDa and 33 kDa and reacts with a monomorphic determinant. The molecular weight of the polypeptides precipitated with SPV-L3 was slightly less than those precipitated with a HLA-DR-specific monoclonal reagent. In addition two-dimensional gel electrophoresis showed that the antigen precipitated by SPV-L3 differed in charge from those precipitated with the anti-HLA-DR antibody. These results indicate that SPV-L3 recognizes a class II MHC product different from HLA-DR. This observation was confirmed by partial amino acid sequence analysis of the two chains which revealed that the molecule precipitated by SPV-L3 is homologous to HLA-DC/DS molecules. Therefore this report provides the first evidence that human cytotoxic T cells can recognize HLA-DC/DS antigens.

Amino Acid Sequence↗
PubMed1984

Phase II and pharmacokinetic study of high-dose methotrexate in the treatment of advanced gynecologic malignancy. A Southwest Oncology Group Trial.

Fifteen patients with advanced or recurrent gynecologic malignancy were treated with high-dose methotrexate (HDMTX) (1-8 g/M2) and citrovorum factor rescue (10-100 mg/M2). One complete response (13%) and two improved responses occurred in eight patients (25%) with squamous cell carcinoma and one of seven patients (14%) with nonsquamous nontrophoblastic carcinoma had stable disease for 7 months. The median duration of survival in the squamous group was 9 months and in the nonsquamous groups 6.5 months. Mean serum MTX concentrations were proportional to the doses administered and typical two compartment plasma disappearance curves were seen. Adverse toxic reactions were not observed at serum MTX levels less than 7.8 X 10(-7) M at 24 hr and 1 X 10(-7) M at 48 hr post-MTX. Hematopoietic toxicity occurred most frequently with leukopenia observed in 19.5% of courses. Hepatic, renal, gastrointestinal, and dermatologic toxicities were observed infrequently. Drug-induced nephrotoxicity occurred in one patient and possibly related leukoencephalopathy occurred in another patient. On the basis of the relatively low response rate observed in this trial and the high expense of HDMTX therapy, the value of such therapy may be limited in advanced nontrophoblastic gynecologic cancer.

Adult↗
PubMed1983

The T3 complex on human T lymphocytes involves four structurally distinct glycoproteins.

Monoclonal antibodies allow for the detection of antigens which are specific for human thymus-derived lymphocytes. Among these antigens, the T3 complex is of particular interest since it is involved in several T cell functions. The main target antigen of the anti-T3 reagents is borne by a 20-kDa glycoprotein. In addition, glycoproteins of 25-28, 37, and 44 kDa are found in anti-T3 immunoprecipitates derived from surface-labeled cells. The four antigens appeared to be strongly associated with each other in detergent-containing solutions. Comparative studies of the four proteins, facilitated by the use of endo-beta-N-acetylglycosaminidase F, revealed that their polypeptide backbones have different molecular weights and pI values. Moreover, peptide maps of the 20-kDa T3 and the 25-28-kDa T3 were quite different. Metabolic labeling experiments suggested that the 25-28-kDa protein might become associated with the 20-kDa T3 antigen during biosynthesis. The 37-kDa and 44-kDa proteins could not, however, be detected and, therefore, might become associated with the 20-kDa T3 on the cell surface. Evidence has been found for the existence of a fifth member of the T3 complex, namely an unglycosylated 20-kDa T3 species.

Antibodies, Monoclonal↗
PubMed1983

The T3 complex on human thymus-derived lymphocytes contains two different subunits of 20 kDa.

The human cell surface antigen T3 is involved in several T lymphocyte specific functions, as determined by the effect of monoclonal antibodies (OKT3, anti-Leu-4, UCHT1) directed at this molecular structure. The main target antigen of these monoclonal antibodies is a glycoprotein of 20 kDa. It is associated with four, less predominant, structurally distinct glycoproteins of 25-28 kDa, 37 kDa and 44 kDa. Of these molecules only the 20-kDa T3 antigen could be labeled with the hydrophobic reagent 5-iodonaphthyl-1-azide (INA). Here we present evidence that the main 20-kDa T3 antigen is comprised of, in fact, two structurally different molecules. One of these is a glycoprotein with a protein backbone of 14 kDa, the other is an unglycosylated protein of 20 kDa. This unglycosylated protein is labeled specifically with INA. Additional evidence for the existence of two different 20-kDa T3 antigens is provided by studies using the enzymes endo-beta-N-acetylglucosaminidase H and endo-beta-N-acetylglucosaminidase F and the drug tunicamycin. We hypothesize that the specific susceptibility to labeling with INA of the unglycosylated 20-kDa T3 form reflects a positioning in the lipid bilayer different from that of the glycosylated 20-kDa T3 form.

Antibodies, Monoclonal↗
PubMed1983

Comparison of various atmospheric conditions for isolation and subcultivation of Mycoplasma hyorhinis from cell cultures.

The efficiency of aerobic incubation was compared with incubation under various oxygen and carbon dioxide conditions for the isolation and subcultivation of three strains of Mycoplasma hyorhinis from VERO-cell cultures and subcultivation of three laboratory strains. Under anaerobic conditions with a low oxidation-reduction potential (at or below -115 mV) as obtained in jars, with catalysts, containing mixtures of 5%-10% CO2 in H2, very poor or no growth of any of the six M. hyorhinis strains was observed. When traces of oxygen were present (that is, under conditions with higher oxidation-reduction potentials, e.g. when omitting the catalyst in the above gas mixtures or in 5% CO2 + 95% N2) isolation from cell cultures was successful in most tests, but subcultivation of these primary isolates was seldom possible under these semi-anaerobic conditions. However, in most cases these primary isolates could be subcultivated aerobically, although aerobic conditions were unsatisfactory for isolation in about half of the experiments. Isolation of M. hyorhinis was optimal in 5% O2 + 95% N2, under which condition the isolates could also always be subcultivated. Isolation failed occasionally when 5% O2 + 5% CO2 + 90% N2 was used, thus indicating that 5% CO2 was slightly inhibitory. 5% CO2 in air and 10% CO2 either in air, H2 or N2 were also inadequate for isolation from cell cultures. In contrast to the findings with these cell culture-adapted M. hyorhinis strains, the laboratory strains could be subcultivated easily under all conditions tested except those with an oxidation-reduction potential at or below -115 mV; 100% CO2 was inhibitory for all 6 strains. Our findings may partly explain why M. hyorhinis is often considered "non-cultivable" on artificial media once adapted to cell cultures. The findings emphasize the need to employ also a micro-aerophilic condition (5% O2 in 95% N2) in the examination of cell cultures for mycoplasma.

Aerobiosis↗
PubMed1983

Target antigen of monoclonal reagent S5.7: comparison with T3 antigen.

S5.7 recognizes a 20 kD cell surface protein which is present on T lymphocytes. S5.7 binds to a nonglycosylated protein, which can be labeled by cell-surface radioiodination and by a hydrophobic reagent [125I]-iodo-5-naphthyl-1-azide (INA). As the T-lymphocyte-specific T3 complex was found to contain a nonglycosylated 20 kD species, and since this 20 kD T3 form can be labeled preferentially by INA, a comparison between T3 and S5.7 was made. Isoelectric focusing experiments showed, however, that the two proteins are different. Moreover, the S5.7 monoclonal antibody does not block CML, is not mitogenic, reacts with immature cells of several hemopoietic lineages, and differs in that respect from anti-T3 monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1983

Characterization of monoclonal antibodies against cell surface molecules associated with cytotoxic activity of natural and activated killer cells and cloned CTL lines.

Supernatants of hybridomas from fused spleen cells of mice immunized with either a T4+ or a T8+ CTL clone, were screened for their ability to inhibit the cytotoxic activity of the T4+ and the T8+ CTL clone. Eight monoclonal antibodies (MAbs) with blocking activity were obtained and a preliminary characterization of these antibodies was carried out. The MAbs SPV-L1 and SPV-L5 were found to react with thymocytes and all peripheral blood leukocytes. SPV-L1 and SPV-L5 precipitated a molecular complex consisting of two noncovalently bound chains of molecular weights of 95 and 160 kD indicating that they recognize the human equivalents of the recently described leukocyte function associated (LFA-1) antigens. The SPV-L1 and SPV-L5 antibodies inhibited the reactivity of six CTL clones tested in this study. In addition, SPV-L1 and L5 blocked the lectin dependent cellular cytotoxicity mediated by these CTL clones. Natural killer cell activity mediated by fresh peripheral blood lymphocytes and activated killer cell activity generated in MLC both measured against K562 was also inhibited by SPV-L1 and SPV-L5. Two other antibodies, SPV-L3 and SPV-L4 blocked strongly the cytotoxic activity of two T4+ CTL clones, whereas the reactivity of the three T8+ CTL clones and one T4+ CTL clone was not or only moderately inhibited. These antibodies recognized an Ia antigen as judged from tissue distribution and immunoprecipitation studies. However, these latter studies also suggest that SPV-L3 and SPV-L4 recognize HLA-DC rather than HLA-DR antigens. Finally, three antibodies (SPV-T3a, SPV-T3b, SPV-T3c) were obtained directed against the T3 molecular complex and one MAb (SPV-T8) was found to react with T8. The anti-T3 reagents were shown to be mitogenic for peripheral blood lymphocytes, with the exception of SPV-T3a. The results presented here indicate that the antigens recognized by SPV-L1 and SPV-L5 are involved in various cytotoxic reactions. In contrast, SPV-L3, SPV-T3 and SPV-T8 only seem to play a role in antigen specific cytotoxic reactions.

Animals↗
PubMed1983

Differentiation antigens of human hemopoietic cells: patterns of reactivity of two monoclonal antibodies.

Two mouse anti-human monoclonal antibodies (S3.13 and S5.7) raised against cells of acute myelogenous leukemia were found to react with antigens expressed on the surface of subsets of monocytes and lymphocytes. S3.13 precipitates a peptide of Mr 29,000, and S5.7 precipitates a peptide of Mr 20,000 present on the surface of all the cell types tested. These two surface antigens were distributed on discrete subpopulations of normal hemopoietic cells. The antibodies reacted with all (S5.7) or a subpopulation (S3.13) of peripheral blood T-lymphocytes, and with a subset of monocytes. Both antibodies reacted with bone marrow blast cell progenitors of the myelomonocytes and erythroid lineage. S5.7 also reacted with non-T-lymphocytes and with cells of the eosinophilic lineage. Both antigens disappeared from the cell surface during normal myeloid and erythroid differentiation. Thus, these monoclonal antibodies define the molecular characteristics and the cellular distribution of two differentiation antigens present on cells of the hemopoietic lineage.

Animals↗
PubMed1982

Complexity of the human T lymphocyte-specific cell surface antigen T3.

A human T lymphocyte cell surface antigen T3 was found to be involved in several functions that were specific for the cells that express this marker on their surface. We show here that several glycoproteins were found in the immunoprecipitates prepared with a monoclonal reagent anti-T3. In addition to the major glycoprotein complex of 20 kd, glycoproteins of 25 to 28 kd, 37 kd, and 44 kd were detected in immunoprecipitates. The charge heterogeneity of the 20 kd and 25 to 28 kd proteins was caused by variable sialic acid content. The 20-kd T3 glycoprotein carried several "complex-type" and endoglycosidase-H-sensitive sugar moieties. We found that the 20-kd protein could be labeled with 125I-iodonaphthylazide, a reagent that reacts with hydrophobic areas of proteins.

Acetylglucosaminidase↗
PubMed1979

Sporadic cases of Legionnaires' disease in the Netherlands.

Sera of 24 patients with an unexplained pneumonia were tested for the presence of antibodies against the Legionnaires' disease bacterium. Fifteen patients had positive serology. The series comprised 12 male and three female patients ranging in age from 17 to 66 years (mean, 51.1 years). All of the patients had a high fever, little or no sputum production, and radiographic evidence of pneumonia. The radiographic abnormalities ranged from a patchy infiltrate to extensive consolidation. In eight patients with confirmed Legionnaires' disease, severe confusion was one of the most striking signs. A variety of antibiotics had no clear effect on the duration of the illness in these cases, although the severity seemed to be influenced. Two of the patients died, and in three the course was protracted. All cases were sporadic. Eight patients had been infected abroad and seven in the Netherlands, two of whom were on immunosuppressive therapy and were infected in a hospital.

Adolescent↗