Search PubMed⌕ Search

Biomedical subjects

B Rubin

Publications and source records attributed to B Rubin.

At least 109 records · Page 6Linked to original sources
PubMed1989

Recognition of insulin on MHC-class-II-expressing L929 cells by antibody and T cells.

In the present experiments, we attempted to obtain evidence that T-cell receptors (Tcr) and immunoglobulins can react against the same antigen-peptide/MHC class II complexes on antigen-presenting cells (APC). Use was made of monoclonal APC, i.e. I-Ak alpha/beta gene-transfected L929 fibroblasts, monoclonal anti-insulin antibodies and selected insulin-specific T-cell lines. Evidence for similarities in antibody and T-cell recognition of insulin presented by I-Ak alpha/beta gene-transfected L-cell fibroblasts was not obtained after serious attempts. Furthermore, we found no evidence for synthesis of antibodies specific for insulin-peptide/MHC class II complexes.

Animals↗
PubMed1989

Preclinical pharmacology of zofenopril, an inhibitor of angiotensin I converting enzyme.

Zofenopril calcium (one-half calcium salt) is a prodrug ester analog of captopril whose biological effects are manifested by its active component, SQ 26,333. Because of the relative insolubilities of both zofenopril calcium and SQ 26,333, zofenopril potassium salt and SQ 26,703, the arginine salt of the active ACE (angiotensin I converting enzyme) inhibitory moiety of zofenopril, were employed in many of the following studies. The in vitro and in vivo pharmacological effects of zofenopril have been evaluated and comparisons have been made to captopril. In vitro, SQ 26,703 was more potent than captopril as an inhibitor of rabbit lung ACE (IC50 = 8 vs. 23 nM). SQ 26,703 was also a potent inhibitor of angiotensin I (AI)-induced contractions (EC50 = 3 nM) and a potentiator of bradykinin-induced contractions (EC50 = 1 nM) of isolated guinea pig ileum, while it had no effect on the inotropic effects of angiotensin II, BaCl2, PGE1, histamine, serotonin, or acetycholine in the same tissue, signifying that zofenopril is a specific inhibitor of ACE. In vivo, the potency of SQ 26,703 was equal to or greater than that of captopril as an inhibitor of an AI pressor response when given intravenously to rats, dogs, and monkeys. After oral administration of equimolar doses, zofenopril was the more effective and longer lasting ACE inhibitor in all three species. In SHR, doses of 6.6 and 22.0 mg/kg, p.o. lowered pressure by 20 and 33 mm Hg, respectively, while 30 mg/kg of captopril lowered pressure by 25 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Fosinopril, a phosphinic acid inhibitor of angiotensin I converting enzyme: in vitro and preclinical in vivo pharmacology.

Fosinopril is the first member of a new chemical class of angiotensin I (AI) converting enzyme (ACE) inhibitors, the phosphinic acids. In vitro, SQ 27,519, the active moiety of the prodrug fosinopril, was a more potent inhibitor of purified rabbit lung ACE- (IC50 = 11 vs. 23 nM) and bradykinin-induced contractions of guinea pig ileum than captopril. In vivo, SQ 27,519 was equipotent to captopril as an inhibitor of an AI pressor response after intravenous (i.v.) administration to conscious rats and monkeys but appeared to be less potent in conscious dogs. After oral administration, fosinopril again was equipotent to captopril as an inhibitor of an AI pressor response in rats and monkeys and slightly less potent in dogs. However, both SQ 27,519 (i.v. studies) and fosinopril (oral studies) had a longer effect than captopril in all three species. When fosinopril was administered orally for 5 days, its effects on an AI pressor response were the same on days 1 and 5, suggesting lack of tolerance to the compound. The ACE inhibitory effect of captopril, but not fosinopril, was prolonged in conscious rats with glycerol-induced acute renal failure, suggesting that fosinopril is excreted by an extrarenal route. Finally, fosinopril had no effect on the pressor or chronotropic effects of norepinephrine (NE) or 1,1-dimethyl-4-phenylpiperinium (DMPP) or electrical stimulation of the sympathetic ganglia of pithed rats. Fosinopril attenuated the pressor, but not the chronotropic effects of tyramine. We conclude that fosinopril is a potent and long-lasting inhibitor of ACE in conscious animal models that does not impair adrenergic function or reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Failure to synthesize the human T-cell CD3-zeta chain and its consequence for the T-cell receptor-CD3 complex expression.

The T-cell antigen receptor is composed of two variable chains (alpha and beta, termed TcR) which confer ligand specificity, and four constant chains (gamma, delta, epsilon, and zeta, collectively termed CD3) whose functions are not fully understood. To explore the role of the individual CD3 components, the human T-cell tumour line Jurkat was chemically mutagenized followed by negative selection with F101.01 (a monoclonal antibody against the TcR-CD3 complex), and cloning. Growing clones were analysed for TcR-CD3 expression by immunofluorescence. One clone, J79, was found to express greatly diminished levels of TcR-CD3. This clone produced all the TcR-CD3 components except the CD3-zeta, as demonstrated by metabolic labelling and immunoprecipitation followed by one- and two-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis. These data indicate that the CD3-zeta determines the normal intracellular fate of the TcR-CD3 complex, and that the CD3-zeta is necessary for the intracellular transport and expression at the cell surface of the TcR-CD3 complex.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

The T-lymphocyte proliferative response to synthetic peptide antigens of defined secondary structure.

Immunodominant sites in proteins recognized by T lymphocytes are segments consisting of at least 7-8 amino acids. It has previously been proposed that these sites in proteins are alpha-helical and amphipatic structures. We synthesized and investigated the immunogenicity of three synthetic peptides (MP7, MP8, and MP9), each consisting of the same 15 amino acids, but differing with respect to sequence. Based on information analysis and circular dichroism measurements, MP7 was shown to have an alpha-helical secondary structure and, based on previously assigned hydrophilicity indices, was also strongly longitudinally amphipatic. MP8 also was conformed as an alpha-helix, but was amphipatic in the sense that the N-terminal half of the molecule was hydrophilic and the C-terminal half hydrophobic. MP9 had neither an amphipatic nor alpha-helical structure. All three peptides were immunogenic in some strains of mice but none was immunogenic in all strains. This supports other studies concluding that amphipaticity per se is neither a necessary nor sufficient requirement for immunogenicity of a peptide. On the other hand, the present experimental data suggest that longitudinally amphipatic alpha-helical peptides may function better as T-cell determinants than the other peptides investigated.

Amino Acid Sequence↗
PubMed1988

Diagnosis of deep vein thrombosis with a new radionuclide method--99Tcm-albumin test.

The diagnostic efficiency of 99Tcm-albumin test (AT), a new radionuclide method, was evaluated in 90 consecutive patients with suspected deep vein thrombosis (DVT) admitted to the medical emergency ward. Phlebography was used as reference method. The sensitivity of the AT test was 92% and the specificity was 61%. As the method is objective, rapid and convenient for the patients, it can be recommended as an initial examination method to be followed by phlebography, in cases with a positive test result. Criteria with high specificity, 98%, have also been defined but these criteria should be further investigated.

Adult↗
PubMed1987

Triazine Resistance without Reduced Vigor in Phalaris paradoxa.

A triazine-resistant (R) biotype of Phalaris paradoxa L. (hood canarygrass) was superior to a triazine-susceptible (S) biotype in seed-germinability and seedling emergence. It was equal or superior to the S-biotype in growth under noncompetitive conditions. Rates of CO(2) uptake by R-plants were similar to those of S-plants, except at very low photon flux densities, where S-plants exhibited higher rates of CO(2) uptake. Fluorescence induction curves of chloroplasts isolated from R-plants indicated an alteration in photosystem II. Analysis of the light dependence of electron transport shows a reduction in quantum yield (Q(y)) in R- compared to S-chloroplasts. The same analysis, however, shows for R-chloroplasts an increase in the light-saturated electron transport rate (V(max)). The increase in V(max) compensates for the reduction of Q(y) over a wide range of photon flux densities, which may explain the similarity between R- and S-biotypes in photosynthetic potential and growth.

Journal Article↗
PubMed1986

Insulin-specific T cell help to TNP-specific B cells requires activation via the antigen T cell receptor.

In the present study, the production of large numbers of insulin (Ins)-specific, H-2-restricted T helper (Th) cell clones is described. Among 148 clones analyzed, 121 clones had Th cell function, and these were divided into 75 Ins-specific Th cell clones and 52 autoreactive clones. The 148 clones were isolated from Ins-specific T cell lines produced by in vitro stimulation of T lymphocytes from (b X d)F1 mice immunized with Ins 7, 14, 32 or 56 days before. The following characteristics were tested with regard to the Th cell clones: restriction specificity and antigen requirement for optimal help or interleukin 2 (IL2) production. No differences in these characteristics were found among clones originating from day 7, 14, 32 or 56 T cell lines. A preference for H-2b as restriction element and an antigen concentration of about 0.01 microgram trinitrophenylated (TNP)-Ins/ml for optimal help were general traits. Optimal IL2 release is not yet obtained with 100 micrograms TNP-Ins/ml. Thus, the antigen requirement for optimal help and IL2 release differs by a factor 10(4) at least. Certain twice-cloned Th cell lines were tested for IL2 production when stimulated with anti-Thy-1 monoclonal antibodies (mAb). All clones analyzed were stimulated by mAb H155 but not with mAb H140 nor with mAb against Lyt-1, L3T4, LFA-1 or H-2K/D molecules. Therefore, we determined whether TNP-conjugated H155 mAb would mediate Th cell-B cell collaboration as well as TNP-Ins. The results with nine different Th cell clones and six different TNP-conjugated mAb used in a 10(7)-fold concentration range showed that Th cell clones have to be triggered via the T cell receptor for expression of helper function to B cells. Thus, though IL2 gene activation, synthesis or release apparently can be activated via at least two pathways: T cell receptor or Thy-1, it seems that activation of the genes responsible for synthesis and release of the helper factors, which ensure antigen-specific B cell proliferation and differentiation, needs Th cell-B contact mediated via the antigen-specific T cell receptor.

Animals↗
PubMed1985

On the molecular basis of T-helper-cell function. IV. B-lymphocyte-promotor factors: on their mode of action, biochemical nature and possible relationship to molecules involved in specific T-helper-cell activity.

Some further aspects of B-lymphocyte-promotor factor (B-LPF) activity have been studied. This activity was present in the supernatants of certain helper-T-cell lines, and it induced polyclonal activation of Ig+ B cells into Ig-secreting cells. It was found that B-LPF induced polyclonal, terminal B-cell differentiation (1) in T-cell- and macrophage-depleted spleen cell populations, (2) in both Lyb-5- and Lyb-5+ cells as well as in small and blast-like splenic B cells, and (3) in normal rather than memory B cells. B-LPF function was neither restricted to major histocompatibility complex gene products nor to immunoglobulin allotypes. B-LPF-like activity was also produced by some B-cell lymphomas/hybrids and by the P388-D1 macrophage line. B-LPF activity was found in three MW fractions: (I) greater than 180,000 (pI greater than 7.0 and 4.5-5.5); (II) 50,000-70,000 (pI greater than 7.0; 6.0-6.5, and 4.5-5.5); and (III) 10,000-15,000 (pI greater than 7.0). All three MW forms of B-LPF activity carried antiserum 6036-defined and AB-1.9.3 monoclonal antibody-defined determinants, and they reacted with chicken gammaglobulin (CGG)-Sepharose but not with human serum albumin-Sepharose. These data indicate that the three MW forms of B-LPF activity are associated/dissociated forms of a 10,000-15,000 MW form (subunit) rather than three different molecular species with B-LPF activity. A comparative study between antigen-specific helper factors and B-LPF was hampered by the finding that the helper-T-cell hybridomas used (e.g., T85-109-45/1) only produced B-LPF in our hands. Previously, it has been described that these helper-T-cell hybrids produced CGG-specific, I-Ak-restricted helper factors. However, one surprising observation was that B-LPF produced by both T85 hybrid cells and L12 T lymphoma cells was absorbed and could be eluted from CGG-Sepharose columns. The relationship of B-LPF to other nonspecific and apparently specific T-helper-cell products is discussed in particular in the light of the observations that many immunologically active molecules are built up from 10,000-12,000 molecular weight domain-like polypeptide structures.

Animals↗
PubMed1985

Murine and human T cell factors that induce the differentiation of normal mouse lymphocytes into cytotoxic cells copurify with interleukin 2.

Fetal calf serum (FCS)-specific T promoter cell lines (line 12), clones, or lymphomas produce lymphocyte promoter factors (LPF). These factors are defined as T-cell supernatant activities that induce polyclonal differentiation of normal experimentally unprimed mouse lymphocytes into antibody-forming cells (B-LPF) or into cytotoxic cells (T-LPF). The cytotoxic cells thus induced lysed a broad range of target cells including syngeneic and allogeneic tumour cells and lymphoblasts. We have investigated whether T cell tumours (mouse or human) other than FCS-specific T promoter cell lines (line 12), clones, or lymphomas produce T-LPF activity, and whether T-LPF activity is related to interleukin 2 (IL-2) activity. We found that the EL4 thymoma cells were high producers of T-LPF and IL-2 activity. When EL4 cells and T-LPF+ line 12 lymphomas were cloned, all T-LPF high-producer clones were also high IL-2 producers. In addition, the human Jurkat T tumour cells produced both T-LPF and IL-2 activity which could be detected on both mouse and human lymphocytes. By using biochemical fractionation (size fractionation or chromatofocusing fractionation) and absorption techniques, we could not separate T-LPF and IL-2 activity. Thus, the present data may indicate that the T-LPF and IL-2 activities studied in the present systems are borne by the same molecule(s) (= IL-2?). These results are discussed in relation to current hypotheses on the cellular and molecular requirements for the generation of cytotoxic T cells.

Animals↗
PubMed1985

Release of granulocyte-macrophage colony stimulating factors from major histocompatibility complex class II antigen-positive monocytes is enhanced by human gamma interferon.

Human gamma interferon (HuIFN gamma) was assessed for its capacity to enhance release of granulocyte-macrophage colony stimulating factors (GM-CSF) from human peripheral blood monocytes. Natural HuIFN gamma (2 X 10(7) NIH reference units per milligram) at concentrations as low as 0.01 U/mL to 10 U/mL reproducibly enhanced release of GM-CSF. This enhancement was detected when T lymphocytes were depleted from monocyte preparations and when T lymphocytes and monocytes were depleted from populations of human bone marrow cells stimulated by monocyte-conditioned media to form colonies and clusters. T lymphocytes alone or in the presence of HuIFN gamma did not release GM-CSF. The enhancing activity of HuIFN gamma was removed by preincubating HuIFN gamma with neutralizing concentrations of monoclonal anti-HuIFN gamma, and recombinant HuIFN gamma mimicked the effects of natural HuIFN gamma, suggesting that the effects were due to HuIFN gamma itself. HuIFN gamma suppression of the release of inhibitory activity from monocytes was ruled out as a reason for the noted enhancing activity of HuIFN gamma. The enhancing activity of HuIFN gamma was confined to the MHC class II antigen-positive population of monocytes. Removal of these cells with monoclonal antibody plus complement (C') ablated the enhancing activity, high concentrations of certain monoclonal antibodies in the absence of C' blocked the enhancing activity and, when monocytes were sorted into MHC class II antigen-positive and -negative cells by fluorescence-activated cell sorting, it was only the positive cell fraction that responded to the enhancing activity of HuIFN gamma.

Cells, Cultured↗
PubMed1985

Medically reversible quadriparesis in tophaceous gout.

This case report presents a successful nonoperative outcome of a type II odontoid fracture secondary to severe tophaceous gout. The patient presented with spastic quadriparesis and tophaceous involvement of the odontoid process with fracture and C1-C2 instability. He refused surgery. However, his odontoid process stabilized with the used of a collar, and he regained almost normal strength plus independence in self-care and ambulation, demonstrating that an unstable type II odontoid fracture secondary to tophaceous gout can stabilize with conservative management.

Axis, Cervical Vertebra↗
PubMed1984

The molecular basis of T helper cell function--I. Allotype- and MHC-linked determinants on antigen-specific, H-2-restricted T cell lines, hybridomas and lymphomas.

A T-cell hybridoma clone, which produces antigen-specific helper factors and a T-cell lymphoma clone which produces non-specific helper factors was used to study the expression of T-cell allotypes and Ia antigens. Use was made of rabbit antisera against isolated T-cell receptor material and of monoclonal mouse antibodies against isolated rat Ia antigen. The rabbit antisera detected endogenously produced determinants both on the membrane and on intracellular polypeptides of these cells. The monoclonal mouse anti-rat-Ia antibodies detected polymorphic determinants on mouse Ia antigens and reacted with endogenously produced molecules on the membrane and on intracellular molecules of the hybridoma and lymphoma cells. The molecules carrying Tcr allotypes were single-chain polypeptides with mol. wts of 60,000-70,000 and the molecules carrying Ia-like antigenic determinants were single-chain polypeptides with mol. wts of 40,000-50,000. Thus T-cell allotypes and Ia antigens were found on separate polypeptide chains. The role and genetic localization of allotype-like and Ia-like molecules in T-cell products is discussed.

Animals↗