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S Shaw

Publications and source records attributed to S Shaw.

At least 379 records · Page 21Linked to original sources
PubMed1985

Susceptibility of cytotoxic T lymphocyte (CTL) clones to inhibition by anti-T3 and anti-T4 (but not anti-LFA-1) monoclonal antibodies varies with the "avidity" of CTL-target interaction.

To explore the role of the T3, T4, and LFA-1 molecules in high and low "avidity" interactions between SB2-specific cytotoxic T lymphocyte (CTL) clones and their targets, monoclonal antibody-mediated inhibition of cytotoxicity has been studied in experiments that vary the "avidity" of interaction in three different ways. 1) Previous results have been extended with respect to different CTL clones assayed on the same SB2-positive target cells. Differences between clones in susceptibility to anti-T3 inhibition paralleled variations in anti-T4 inhibition, and both correlated inversely with the "avidity" of the effector-target interaction (inferred previously from studies of conjugate dissociation). 2) A high "avidity" clone, 8.4, was identified that lysed not only SB2-positive cells but also cross-reacted on a few SB2-negative cells. Cold target inhibition studies confirmed the cross-reaction, and together with conjugate dissociation studies, indicated that cross-reaction to be of lower "avidity" than the specific recognition of SB2. Cross-reactive lysis was much more susceptible to inhibition by anti-T3 and anti-T4 than was specific lysis. 3) Anti-T3 and anti-T4 blocking was analyzed in the presence of anti-Ia antibody to reduce the amount of Ia antigen available on the target. Anti-T3 and anti-T4 antibody blocking was more efficient after the addition of anti-Ia antibody concentrations that (by themselves) produced minimal inhibition of lysis. As a control, anti-LFA-1 antibody blocking was analyzed in each of these three experimental systems that compare interactions of different "avidity"; minimal variation was observed in the efficiency of inhibition by anti-LFA-1. Thus, anti-T3 and anti-T4 inhibition correlates inversely with the "avidity" of that CTL-target interaction, but anti-LFA-1 inhibition does not.

Adult↗
PubMed1985

Effects of human atrial natriuretic peptide on the pressor action of noradrenaline and angiotensin II in normal subjects.

The newly synthesized human alpha-atrial natriuretic peptide(alpha-hANP)(molecular weight 3082.6) was injected intravenously at stepwise increasing doses of 10, 40 and 75 micrograms into eight normal subjects (mean age +/- s.d. 24 +/- 1 years). The highest dose decreased blood pressure (BP) only slightly under basal conditions (from 118/76 +/- 8/10 to 111/71 +/- 10/13 mmHg, P < 0.005 for systolic BP) and insignificantly during angiotensin II (ANG II) pressor infusion (from 134/98 +/- 9/10 to 137/93 +/- 12/14 mmHg). In contrast, during a noradrenaline (NA) pressor infusion, BP was lowered progressively by the three alpha-hANP doses from 163/96 +/- 12/11 to 156/88 +/- 9/11 (P < 0.02), 148/78 +/- 12/7 (P < 0.001) and 148/70 +/- 10/13 mmHg (P < 0.001), respectively. Heart rate was increased similarly (P < 0.001) by a alpha-hANP during (from 51 +/- 10 to 63 +/- 12 beats/min) or ANG II infusion (from 53 +/- 5 to 64 +/- 10 beats/min). Effects were maximal from 1 to 4 min, lasting for 10 min. These observations reveal that alpha-hANP possesses vasoactive properties independent of a natriuretic action in normal subjects. Alpha-atrial natriuretic peptide may interact preferentially with noradrenergic as compared with angiotensinergic blood pressure control mechanisms.

Adult↗
PubMed1985

Anti-T3 antibody both activates and inhibits the cytotoxic activity of human T cell clones.

The present report outlines results using several approaches to investigate the effects of antibodies against cell surface molecules on human cytotoxic T lymphocyte (CTL) recognition. First, when interactions between CTL and targets are perturbed by antibody immobilized on the surface of the incubation vessel, anti-T3 antibody was unique in its ability to inhibit at least 10 times more efficiently than when present in solution. Second, anti-T3 antibody at sufficiently high concentrations inhibits lectin-dependent cellular cytotoxicity as well as allospecific cytotoxicity. Third, murine hybridomas expressing anti-T3 antibody induce their own lysis by human CTL clones; but hybridomas bearing antibodies of other specificities are not lysed in a similar manner. We have exploited this anti-T3 triggered lysis of the OKT3 hybridoma as a model system in which to study T cell recognition. Such lysis is susceptible to inhibition not only by anti-T3 but also by anti-LFA-1 antibody; however, conjugate formation between the anti-T3 hybridoma and CTL is not easily inhibited by anti-LFA-1. These data, which are discussed in the context of results from other laboratories, are consistent with a model in which CTL triggering can be induced by interaction of the antigen specific receptor (Ti) with its physiologic ligand, antigen plus MHC, or interaction of the T3 complex with a surrogate ligand, anti-T3/anti-Ti. However, they raise questions regarding the role which LFA-1 plays in CTL recognition.

Animals↗
PubMed1984

Depression of biliary glutathione excretion by chronic ethanol feeding in the rat.

The effects of chronic alcohol feeding on biliary glutathione excretion were studied in rats pair fed diets containing either ethanol (36% of total energy) or isocaloric carbohydrate for 4-6 weeks. An exteriorized biliary-duodenal fistula was established and total glutathione (GSH) and oxidized glutathione (GSSG) were measured. A significant decrease was observed in rats fed alcohol chronically compared to their pair fed controls in the biliary excretion of GSH (55.7 +/- 37.0 vs 243.1 +/- 29.0 micrograms/ml bile, p less than 0.025) as well as biliary GSSG (12.5 +/- 5.0 vs 49.9 +/- 8.0 micrograms/ml bile, p less than 0.05) and in bile flow (23.1 +/- 1.6 vs 29.2 +/- 1.3 micrograms/min, p less than 0.05). An acute dose of ethanol tended to exaggerate the decrease on biliary GSH and GSSG in the two groups of animals. The depression in biliary GSH could not be attributed to decreased GSH synthesis since S35-L-methionine incorporation into hepatic and biliary GSH was unchanged or even increased after chronic ethanol feeding.

Animals↗
PubMed1984

Possible involvement of the T4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of CTL-target cell binding.

The present study examines the potential role of the T4 molecule in functional cell-cell interactions between target cells and human cytotoxic T lymphocyte (CTL) clones that are specific for HLA class II alloantigens encoded by the SB locus. There were marked differences (greater than 30-fold) between the seven SB-specific clones studied with respect to their susceptibility to inhibition by anti-T4 as well as anti-T3 antibodies. We wished to test the hypothesis that such variation among the clones would be due to differences in clonal "affinity" for antigen. To quantitate differences among the CTL clones in the tightness with which they bind target cells, the clones were analyzed using a previously published assay of susceptibility of CTL-target cell conjugates to dissociation in the presence of unlabeled targets. The results revealed that the clones that were most susceptible to inhibition by anti-T4 and anti-T3 were the weakest target cell binders, and vice versa. Anti-T4 antibody could partially induce dissociation of functional CTL-target cell conjugates in the absence of any added cold targets. For the "highest affinity" clone such anti-T4 antibody-induced dissociation could be observed at 4 degrees C but not 23 degrees C. These results indicate that the T4 molecule is functionally involved in target cell binding by CTL, and raise the possibility that although it is easiest to demonstrate the function of the T4 molecule in "low affinity" clones, that function may also be operative in the "high affinity" clones.

Adult↗
PubMed1984

The effect of chronic alcohol feeding on lipid peroxidation in microsomes: lack of relationship to hydroxyl radical generation.

Chronic alcohol feeding causes microsomal induction including increased generation of hydroxyl radicals. Ethanol induced liver injury may be mediated by lipid peroxidation for which hydroxyl radicals have been proposed as major mediators. Ethanol promotes lipid peroxidation when given acutely but also may serve as a hydroxyl radical scavenger. Therefore, we studied the acute and chronic effects of alcohol on microsomal lipid peroxidation and hydroxyl radical generation. Chronic alcohol feeding in rats increased microsomal generation of hydroxyl radicals but lipid peroxidation of endogenous lipid was inversely related to hydroxyl radical generation. Ethanol (50mM) had a slight inhibitory effect on hydroxyl radical production in peroxidizing microsomes, no effect on endogenous lipid peroxidation and enhanced the lysis of RBCs added as targets of peroxidation. Enhanced microsomal generation of hydroxyl radicals following chronic alcohol feeding is not an important mediator of lipid peroxidation.

Alcoholism↗
PubMed1984

Depression, suicide, and aggression in alcoholics and their relationship to plasma amino acids.

In an earlier study we found an association in alcoholic patients between depression and low ratios of tryptophan over amino acids sharing with it the same transport carrier into the brain. A decreased tryptophan ratio has been shown to be correlated with lower brain tryptophan and serotonin. Because it has been postulated that altered serotonin metabolism may be a highly significant contributing factor not only to depression but also to aggressive and suicidal behavior, we decided to assess the existence of possible associations between amino acid abnormalities and these behaviors in a population of alcoholics. We observed a significant association between histories of aggression and depression. In addition, depressed patients with a history of aggression were found to have the lowest tryptophan ratio values. These values differed significantly from those found in depressed patients with no aggression history and from those observed in patients with no history of aggression and depression. Two of the three suicide attempters in the study fell also in the group of patients with an aggression history. Our data suggest the existence of a subgroup of alcoholics with marked amino acid abnormalities at risk for manifestations of depression, suicide, and aggression.

Adult↗
PubMed1984

Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigens.

Mutant human B-lymphoblastoid cell lines, 721.174 and 721.180, that have greatly reduced expressions of known class I and class II HLA antigens were produced by two cycles of gamma-ray mutagenesis followed by selection for HLA antigen loss. Residual binding of monoclonal antibodies directed against class II antigens was negligible except for 10% residual binding of SB-binding antibody ILR1. However, deletion of SB was functionally complete as indicated by failure of the mutants to stimulate proliferation of SB-primed lymphocytes. Residual binding of monoclonal antibodies directed against class I "framework" determinants was reduced by 90-95%. However, the binding of monoclonal antibodies directed against beta 2-microglobulin and against the A2 epitope recognized by monoclonal antibody BB 7.2 was about 20% of normal. The identities of the residual class I-like antigens are unknown. The mutants retained full expression of the EBV-induced EBVCS antigen. Mutants 721.174 and 721.180 have lost most, but definitely not all, of their capacity to stimulate primary allogeneic and autologous lymphoproliferative responses. Therefore, the mutants still express antigens other than those that are presently known to stimulate lymphocyte proliferation. By means of studies of the present sort, and in future studies on expression of transferred HLA genes, mutants 721.174 and 721.180 promise to be useful in molecular and functional analysis of MHC-region-encoded gene products and their genetic regulation.

Antibodies, Monoclonal↗
PubMed1984

Characteristics of five monoclonal anti-alpha-fetoprotein antibodies.

Five monoclonal anti-alpha-fetoprotein (AFP) antibodies (IgG1) were isolated from six fusions. They were characterized by examining titration values, affinity constants, isotypes, and epitope binding. Employing an epitope-blocking procedure which was based on the exclusion of like antibodies, four of the five monoclonal antibodies were found to be different. Antibody individuality was further demonstrated by comparison of isoelectric focusing patterns. The existence of four distinct anti-AFP antibodies strongly suggests the presence of at least that many epitopes on the AFP molecule.

Animals↗
PubMed1984

The gene frequency of SB alleles in the Japanese population.

The gene frequency (+/- SD) of SB alleles was estimated in the Japanese population as follows: SB1 0.00, SB2 0.195 +/- 0.027, SB3 0.070 +/- 0.017, SB4 0.091 +/- 0.019, SB5 0.335 +/- 0.034 and SB blank 0.308 +/- 0.035. The absence of SB1 allele, decrease of SB4 allele and increase of SB5 allele are characteristic features of the SB system in the Japanese population as compared with Caucasians.

Alleles↗
PubMed1984

HLA-linked SB antigens in Israel. Population study, analysis of homozygous typing cells and generation of local SB reagents.

In the present study we have investigated the HLA-SB antigen distribution in 65 unrelated Israeli Ashkenazim and non-Ashkenazim and in a panel of 18 local homozygous typing cells (HTC). Two locally derived SB reagents, anti-SB2 and SB3, were also studied. The HLA-SB allele frequencies in the Israeli sample ranged from 0.02 for SB1 to 0.47 for SB4 while SB5 was absent. SB3 had a higher frequency in non-Ashkenazim (0.11) as compared to Ashkenazim (0.06) but this difference was not significant. On the whole, the allele frequencies for the 5 HLA-SB antigens studied were in the range observed in non-Jewish Caucasoid populations with some minor variations. Two of eighteen local HTC's were found heterozygous for SB, demonstrating that homozygosity for HLA-A, B, C, D and DR does not indicate homozygosity for HLA-SB. The local anti-SB2 and SB3 typing reagents gave concordant results when compared with the NIH reference typing cells in population studies.

Europe↗
PubMed1984

Evidence that 1,25-dihydroxyvitamin D3 inhibits the hepatic production of 25-hydroxyvitamin D in man.

Previous in vitro studies in rachitic rat liver suggested that 1,25-dihydroxyvitamin D inhibits the hepatic production of 25-hydroxyvitamin D (25-OHD). An investigation therefore was carried out in eight normal subjects to determine whether concomitant administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] would alter the response of serum 25-OHD to challenge with vitamin D. In control studies, vitamin D, 100,000 U/d for 4 d, significantly increased mean serum 25-OHD, from 26.3 +/- 2.9 to 66.7 +/- 12.6 ng/ml (P less than 0.01). In contrast, 1,25(OH)2D3, 2 micrograms/d for 4 d, completely prevented an increase in serum 25-OHD in response to the same dose of vitamin D in the same individuals (25.1 +/- 2.2 vs. 27.4 +/- 5.3 ng/ml, NS). In a post-control study in seven of the normal subjects, vitamin D again significantly increased mean serum 25-OHD, from 18.2 +/- 3.1 to 42.8 +/- 4.7 ng/ml (P less than 0.001). In each of the three studies, mean serum calcium, phosphorus, and creatinine did not change and remained within the normal range. Whereas mean urinary calcium did not change in response to vitamin D alone during the 4 d of the two control studies, it increased significantly in the study in which vitamin D and 1,25(OH)2D3 were given together. A dose-response inhibition of the response of serum 25-OHD to vitamin D by 1,25(OH)2D3 was demonstrated in two of the normal subjects. The results provide evidence that 1,25(OH)2D3 inhibits the hepatic synthesis of its precursor 25-OHD in man.

25-Hydroxyvitamin D 2↗
PubMed1984

Relationship between changes in plasma amino acids and depression in alcoholic patients.

The authors studied the relationship between changes in amino acid precursors of biogenic amines and depression in 42 alcoholic patients with a secondary depression. Tryptophan and amino acids competing with it for brain entry were measured in the plasma of depressed alcoholics, nondepressed alcoholics, and control subjects. The ratio of tryptophan to its competitors was significantly lower in depressed patients than in nondepressed patients and controls. The decreased ratio was due primarily to decreased tryptophan and increased tyrosine and phenylalanine values. A decreased tryptophan ratio is known to result in decreased brain tryptophan and may contribute to depression through a deficiency of brain serotonin.

Adult↗
PubMed1984

Comparison of structural and functional variation in class I HLA molecules: the role of charged amino acid substitutions.

Functional and structural heterogeneity of HLA class I molecules was sought among five donors serologically identical for A2, A3, B7, and Bw44. Functional differences were identified by cell-mediated lympholysis (CML) after allogeneic mixed lymphocyte reaction among the five donors. Structural differences were characterized by high resolution two-dimensional electrophoretic maps of the class I HLA proteins synthesized by peripheral blood lymphocytes of these donors. Cells from three donors showed no CML-defined differences from one another; their HLA protein maps were identical. The cells of one donor recognized an A3-associated target antigen on the cells of all the other donors; her HLA map revealed a unique protein with altered isoelectric point. Another donor's cells differed by two CML-detected antigens: one was identified as a variant of Bw44 ("44.2") and the other was associated with Cw4. This donor's two-dimensional HLA map showed two novel charged proteins. By using these data, a two-dimensional map locating HLA-A2, -A3, -A3', -B7, -Bw44.1, -Bw44.2, and -Cw4 was prepared. Because each of three CML-detected antigens was correlated with a protein of distinctive charge, our results and the available published data raise the possibility that amino acid substitution producing charge variation may be a particularly important mechanism in the generation of CML-detectable HLA diversity.

Amino Acids↗