Search PubMed⌕ Search

Biomedical subjects

S S Patel

Publications and source records attributed to S S Patel.

84 records · Page 5Linked to original sources
PubMed1988

Phenotypic and functional characterization of human T cell clones.

The capacity of human peripheral blood-derived T cell clones to carry out a variety of functions was examined. T cell clones were generated by stimulating individual peripheral blood T cells with PHA by a procedure that yielded a growing clone from a mean of greater than 92% of the cultured cells. A total of 65 T cell clones (44 CD4+ and 21 CD8+) generated from two individual donors were examined for their functional capabilities. All T cell clones examined secreted IL-2, IFN-gamma, and lymphotoxin/tumor necrosis factor like activity when stimulated with immobilized mAb to the CD3 complex (64.1). When 54 additional T cell clones from a third donor were analyzed, all were found to produce IL-2. Upon activation with immobilized 64.1, all CD4+ clones and 91% of the CD8+ clones induced the generation of Ig-secreting cells from purified B cells. The CD8+ clones that did not serve as Th cells alone were able to augment the capacity of fresh CD4+ cells to generate Ig-secreting cells. Each of these clones was also found to effect MHC-unrestricted cytotoxicity upon activation with immobilized 64.1. The CD8+ clones were somewhat more effective killers than CD4+ clones, although there was considerable overlap. A total of 18 clones was analyzed for TCR beta-chain gene rearrangement. Of the clones exhibiting rearrangements of the beta-chain gene, 94% were found to have a single rearrangement pattern. Finally, the detailed phenotype of 15 (11 CD4+ and 4 CD8+) of these clones was examined. Variable numbers of cells of each of the clones expressed Ag identified by mAb 4B4 (CD29), Leu 8, Leu 15 (CD11b), and NKH1. Moreover, cells of 6 of 11 CD4+ clones and 4 of 4 CD8+ clones also expressed CD45R in addition to CD29; expression of CD45R and CD29 varied with the activation status of the clone. The current data demonstrate that nearly all of the T cell clones were able to accomplish each of the functions examined regardless of the surface phenotype. Inasmuch as the clones were generated using a technique that expanded more than 92% of the circulating T cells, the data imply that the progeny of the vast majority of T cells may have the inherent capacity to exert a wide array of functional activities.

Adult↗
PubMed1988

Decay-accelerating factor functions as a signal transducing molecule for human T cells.

Decay-accelerating factor (DAF) is a cell surface protein that protects cells from autologous C-mediated lysis. DAF is one of the first phosphatidylinositol-linked molecules to be described on human T cells. The current studies demonstrate that low levels of DAF are expressed on a majority of freshly isolated human T cells and that DAF expression rapidly increases after T cell activation by mitogens. Moreover, antibodies to DAF induce T cell proliferation when the cells are co-stimulated with phorbol esters. The induction of proliferation is facilitated when the antibodies to DAF cross-linked with a secondary antibody. T cell mitogenesis is largely dependent on the phosphatidylinositol-linked form of DAF, because removal of DAF by a phosphatidylinositol-specific phospholipase C eliminates anti-DAF-induced T cell proliferation. These studies suggest that DAF on the surface of T cells may not only serve to afford protection from autologous C but may also function to transmit signals that induce T cell activation.

Adult↗
PubMed1988

Acetyl coenzyme A synthetase catalyzed reactions of coenzyme A with alpha, beta-unsaturated carboxylic acids.

alpha, beta-Unsaturated coenzyme A (CoA) thioesters including acrylyl CoA, methacrylyl CoA, and propiolyl CoA were synthesized by catalysis with acetyl CoA synthetase (EC 6.2.1.1.). After isolation from the enzymatic reactions, the products were found to be the result of 1,4 addition of CoASH to the double bond and addition of water to the triple bond of the initial acyl CoA adducts. Structural determinations of these products by 1H NMR, 13C NMR, and the chemical reactions leading to their formation are described.

Acetate-CoA Ligase↗
PubMed1988

Anti-CD3 and phorbol myristate acetate regulation of MHC unrestricted T cell cytotoxicity. Lack of a requirement for CD3/T cell receptor complex expression during tumor cell lysis.

The effects of anti-CD3 mAb on MHC-unrestricted cytotoxic activity of NK depleted PHA-activated human T cells were examined. Anti-CD3 mAb had variable effects on killing of K562 or Daudi targets. Whereas lower concentrations of OKT3 often inhibited lysis of either target, higher concentrations (greater than 1 micrograms/ml) frequently increased K562 killing and always augmented Daudi lysis. However, lysis of the renal cell carcinoma, Cur, was consistently inhibited by OKT3 over a broad concentration range. Such variable effects were not related to differential regulation of heterogeneous subsets of effector cells, as similar patterns of OKT3-mediated modulation of tumor cell lysis by T cell clones was also observed. Another IgG2a anti-CD3 mAb, 64.1, and either F(ab')2 fragments of OKT3 or intact OKT3 in the presence of aggregated human Ig were found to inhibit lysis of Cur, K562, and Daudi targets consistently. Additional experiments were carried out to determine whether modulation of CD3 accounted for the inhibitory effects of the anti-CD3 mAb. PMA was noted to cause modulation of CD3 from the surface of PHA or alloantigen-activated T cells, and the combination of anti-CD3 and PMA caused even more marked modulation of CD3. Whereas preincubation with PMA and/or anti-CD3 decreased alloantigen-specific cytotoxic T cell function in relative proportion to the loss of CD3 expression, no consistent relationship between CD3 expression and the capacity of PHA-activated T cells to kill Cur targets was noted. PMA alone caused no consistent alteration of Cur lysis. Moreover, in the presence of PMA, anti-CD3 mAb caused no significant inhibitory effect on Cur lysis, in spite of increased modulation and in some cases virtual total loss of surface CD3 expression. These findings indicate that when FcR interactions are prevented, anti-CD3 mAb consistently inhibit MHC-unrestricted cytotoxicity by PHA-activated T cells. Despite this, the data support the conclusion that CD3/TCR complex interactions with target cells are not required for either target cell recognition or triggering of lysis by MHC-unrestricted cytotoxic T cells.

Antigen-Antibody Reactions↗
PubMed1988

Alpha adrenergic blocking activity of urapidil in man.

Urapidil is a new antihypertensive vasodilator agent whose pharmacologic action in man has not yet been fully defined. We have assessed the alpha adrenergic blocking activity of urapidil 15 and 30 mg given intravenously in a single blind study in 8 healthy volunteers. Urapidil produced dose-dependent parallel shift of the phenylephrine log dose/blood pressure response curve, consistent with significant competitive peripheral alpha 1 antagonism. Mean dose ratios were 2.99 and 5.48 for the 15 mg and 30 mg doses respectively. The pA2 for alpha 1 blockade is 7.3. Given these data, the major mechanism of antihypertensive effect of urapidil may be alpha 1 antagonism in the peripheral vasculature.

Adrenergic alpha-Antagonists↗
PubMed1987

Major histocompatibility complex-unrestricted cytolytic activity of human T cells. Analysis of precursor frequency and effector phenotype.

The frequency and phenotype of human T cells that mediate major histocompatibility complex (MHC)-unrestricted cytolysis were analyzed. T cell clones were generated by culturing adherent cell-depleted peripheral blood mononuclear cells at a density of 0.3 cell/well with phytohemagglutinin, recombinant interleukin 2 (rIL-2), and irradiated autologous peripheral blood mononuclear cells and/or Epstein-Barr virus-transformed lymphoblastoid cell lines. These conditions were shown to expand a mean of 96% of cells cultured. All of the 198 clones generated by this method were T cells (CD2+, CD3+, CD4+ or CD2+, CD3+, CD8+) that possessed potent lytic activity against K562, an erythroleukemia line sensitive to lysis by human natural killer cells, and Cur, a renal carcinoma cell line resistant to human natural killer activity. Cytolysis was MHC-unrestricted, since the clones were able to lyse MHC class I or class II negative targets, as well as MHC class I and class II negative targets. In addition, the activity was not inhibited by monoclonal antibodies directed against class I or class II nonpolymorphic MHC determinants. Killing, however, was inhibited by soluble monoclonal antibodies against the CD3 complex. Although the clones produced tissue necrosis factor/lymphotoxin-like molecules, lysis of Cur or K562 was not mediated by a soluble factor secreted by the clones. Some of the clones retained their cytotoxic activity when grown in rIL-2 alone for 4 to 6 wk, whereas others exhibited markedly diminished cytotoxicity after maintenance in this manner. Clones that exhibited diminished or no cytotoxic activity after prolonged maintenance in rIL-2 could be induced to kill by stimulation with immobilized but not soluble monoclonal antibodies to CD3 in the absence of lectin. All of the clones examined expressed NKH1 and CD11b but none were CD16 positive. The degree of cytotoxicity of resting or activated clones could not be correlated with expression of these markers. These data indicate that the capacity for MHC-unrestricted tumoricidal activity and expression of NKH1 and CD11b, but not CD16, are properties common to all or nearly all human peripheral blood-derived T cell clones regardless of CD4 or CD8 phenotype.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Substrate specificity of acetyl coenzyme A synthetase.

Acetyl coenzyme A synthetase (EC 6.2.1.1) has been examined for its ability to accept various carboxylic acids as substrates in place of acetic acid. The activity of the enzyme with these substrates was monitored using a coupled enzyme assay and high pressure liquid chromatography (HPLC) analysis. Short chain carboxylic acids were found to be active including: propionic, acrylic, fluoroacetic, methacrylic, 3-chloropropionic, 3-bromopropionic, and propiolic. The kinetic parameters, Km and % Vmax of the carboxylic acid substrates, are reported and show that these acids are poorer substrates than acetic acid. Several of the acyl CoAs were synthesized on a preparative scale using enzyme catalysis, purified using preparative HPLC, and characterized using proton NMR spectroscopy. In the course of the NMR identification, a complete and fully resolved spectral assignment for all the protons of coenzyme A was made and is reported. The acyl-CoA analogs should be useful as substrate analogs and as potential affinity labels for enzymes that bind acetyl-CoA.

Acetate-CoA Ligase↗
PubMed1986

The assessment of the beta-blocking activity of urapidil: a new method.

Urapidil is an antihypertensive vasodilator agent whose pharmacological action in man has not yet been fully defined. We have assessed the beta blocking activity of urapidil 15 mg and 30 mg i.v. in a single blind study of 10 healthy male volunteers. Urapidil at plasma concentrations in the same range as those shown to have antihypertensive affect did not significantly attenuate the chronotropic effect of isoproterenol. Propranolol 5 mg iv, the positive control, significantly shifted the isoproterenol dose-response curve to the right. We describe a new method of analyzing incomplete dose response curves whereby a linear terminal segment can be reproducibly defined.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Nitroglycerin for rapid tocolysis: development of a protocol and a literature review.

OBJECTIVE: A protocol for nitroglycerin (NTG) use based on experiences with regard to new and previously described obstetric cases is presented. The efficacy of NTG tocolysis for obstetric emergencies is clinically evaluated. STUDY DESIGN: Hemodynamically stable parturients requiring acute tocolysis were treated with intravenous NTG and closely monitored. Clinical information was subsequently abstracted from medical records and compared with data from previous reviews. RESULTS: Tocolytic treatment was successful in all cases (22 of 22, 100%). Complications were clinically insignificant. The most common problem was transient hypotension, which occurred in 9 of 22 (41%) cases. CONCLUSION: NTG is an effective tocolytic with minimal complications, rapid onset, and a brief half-life. These characteristics favor its use during select obstetric procedures. However, strict adherence to protocols for administration is advised.

Clinical Protocols↗
PubMedDate not supplied

Inhibition of alpha4 integrin and ICAM-1 markedly attenuate macrophage homing to atherosclerotic plaques in ApoE-deficient mice.

BACKGROUND: Monocytes/macrophages play a central role in many stages of development of atherosclerotic plaques, including the conversion to an unstable morphology with rupture and fissuring. A better understanding of the mechanism of attachment of monocytes to activated endothelial cells would prove useful in developing strategies aimed at blocking this initial step. Here we describe a novel in vivo model that directly demonstrates homing of macrophages to atherosclerotic plaques. METHODS AND RESULTS: Macrophages were loaded with fluorescent microspheres and injected intravenously into 40-week-old apolipoprotein E-deficient mice. After 48 hours, labeled macrophages were observed adhering to all stages of atherosclerotic plaques from the early fatty streak to mature calcified lesion. The mean number of macrophages adherent to atherosclerotic plaques located in the proximal 1 mm of the aortic root was quantitated by counting serial frozen sections and found to be 143 +/- 17 macrophages per aortic root. Pretreatment of the apolipoprotein E-deficient mice with monoclonal antibodies directed against the alpha-subunit of the alpha4beta1 integrin and against intracellular cell adhesion molecule (ICAM-1) reduced macrophage homing by 75% and 65%, respectively, as compared with isotype-matched controls (P<.05). Pretreatment with a monoclonal antibody directed against E-selectin did not significantly reduce macrophage homing. CONCLUSIONS: These data demonstrate that alpha4 integrin and ICAM-1 play major roles in the recruitment of macrophages to atherosclerotic plaques, whereas E-selectin does not appear to contribute significantly to macrophage recruitment. This model will be useful for studying the mechanism of macrophage recruitment to atherosclerotic plaques and for evaluating the efficacy of inhibitors to adhesion molecules in preventing macrophage recruitment.

Animals↗