Search PubMed⌕ Search

Biomedical subjects

S M Cooper

Publications and source records attributed to S M Cooper.

13 recordsLinked to original sources
PubMed1992

CD2 expression correlates with proliferative capacity of alpha beta + or gamma delta + CD4-CD8- T cells in lpr mice.

The T lymphocytes that accumulate in vast numbers in the lymphoid tissues of lpr/lpr (lpr) mice express a TCR-alpha beta that is polyclonally rearranged, and yet is devoid of surface CD4 or CD8 (CD4-8-) as well as CD2. lpr CD2- alpha beta + CD4-8- T cells exhibit an apparent block in signal transduction, in that when activated they produce little or no IL-2 and proliferate minimally in the absence of exogenous IL-2. In contrast to the predominant hyporesponsive alpha beta + CD4-8- T cells, we observe that a minor subset (1 to 2%) of lpr lymph node CD4-8- cells expresses a TCR-gamma delta and can proliferate upon activation with PMA and ionomycin in the absence of exogenous IL-2. Furthermore, these responsive gamma delta T cells express surface CD2. The functional and phenotypic distinctions of lpr gamma delta T cells led us to identify an analogous minor (4 to 10%) subset of alpha beta + CD4-8- cells in lpr thymus and lymph nodes that does express CD2. Similar to the gamma delta subset, these CD2+ alpha beta + CD4-8- cells are also capable of proliferation and IL-2 production. Thus the capacity for IL-2 production and proliferation by a small proportion of lpr CD4-8- T cells, either alpha beta + or gamma delta +, correlates with their expression of surface CD2. This correlation is supported by the observation that the lpr liver contains actively cycling alpha beta + CD4-8- lymphocytes that are strikingly enriched for CD2 expression. Consequently, unlike the vast proportion of abnormal lpr CD2- CD3+ CD4-8- cells, the CD2+ CD3+ CD4-8- T cells may not express the basic lpr defect, or else are not affected by its presence. These studies suggest that expression of the lpr abnormality may be restricted to a particular T cell lineage. This functional correlation with CD2 expression may be more broadly applicable to phenotypically similar subsets of normal thymocytes, and possibly peripheral tolerized T lymphocytes.

Animals↗
PubMed1992

The relationship between paroxetine and the sparteine oxidation polymorphism.

The relationship between the selective serotonin reuptake inhibitor paroxetine and the sparteine oxidation polymorphism was investigated in a combined single-dose (30 mg) and steady-state (30 mg/day for 2 weeks) study including a panel of nine extensive metabolizers and eight poor metabolizers of sparteine. The median area under the plasma concentration-time curve (AUC) after the first paroxetine dose was about seven times higher in poor metabolizers than in extensive metabolizers (3910 versus 550 nmol.hr/L), whereas at steady state the median AUCss tau interphenotype difference was only twofold (4410 versus 2550 nmol.hr/L). Plasma half-life and steady-state plasma concentration were significantly longer and higher, respectively, in poor metabolizers than in extensive metabolizers (41 versus 16 hours and 151 versus 81 nmol/L). Paroxetine pharmacokinetics were linear in poor metabolizers and nonlinear only in extensive metabolizers. Sparteine metabolic ratio (MR = 12 hour urinary ratio of sparteine/dehydrosparteine), increased during treatment with paroxetine in subjects who were extensive metabolizers, and after 14 days treatment two extensive metabolizers were phenotyped as poor metabolizers and the remaining extensive metabolizers were changed into extremely slow extensive metabolizers with sparteine MRs of 5.7 to 16.5. The inhibition of sparteine metabolism was rapidly reversed after cessation of paroxetine administration. In the poor metabolizers there were no significant changes in MRs during the study. It is concluded that paroxetine and sparteine metabolism cosegregates, but the interphenotype difference in metabolism was less prominent at steady state than after a single dose, presumably because of saturation of the sparteine oxygenase (CYP2D6) in subjects who were extensive metabolizers. Paroxetine is a potent inhibitor of sparteine oxidation by CYP2D6 in vivo.

Adult↗
PubMed1979

Increase in fibronectin in the deep dermis of involved skin in progressive systemic sclerosis.

The distribution and amount of fibronectin in both involved and uninvolved skin from scleroderma patients and controls were compared by indirect immunofluorescence. A marked increase in fibronectin was found in the deep dermis of involved scleroderma skin, while the subepidermal papillary regions of all specimens revealed little variation in fibronectin content. The districution of the accumulated fibronectin appeared to parallel that of the accumulated collagen in the involved reticular dermis.

Adult↗
PubMed1978

Stereospecific biosynthesis of triacylglycerols in mammary glands from lactating rats.

Microsomal plus cytosol preparations from the mammary gland of lactating rats are capable of incorporating palmitic acid and oleic acid into triacylglycerols. These triacylglycerols are similar in structure to those found in rat milk, where palmitic acid tends to be confined to the sn-2-position of the glycerol. Both glycerol 3-phosphate and dihydroxyacetone phosphate function as acyl acceptors. The enzymic synthesis of triacylglycerols appears in late pregnancy, increases rapidly during early lactation, but disappears within 3 days of weaning.

Animals↗
PubMed1978

Selective decrease in antibody-dependent cell-mediated cytotoxicity in systemic lupus erythematosus and progressive systemic sclerosis.

With the use of two target cells (chicken erythrocytes and Chang cells), the antibody-dependent cell-mediated cytotoxicity (ADCMC) of peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) was studied. Patients with active SLE had a significant reduction in ADCMC against Chang cells whereas cytotoxicity against chicken erythrocytes did not differ significantly from that of a control population. Similarly, a group of PSS patients with positive anti-DNP antibodies demonstrated a selective reduction in ADCMC against Chang cells. These findings support the concept that different effector cells mediate ADCMC against chicken erythrocytes and Chang cells, and indicate that in some patients with SLE and PSS there is a selective reduction or blockade of the ADCMC effector cell active against Chang cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

Characterization of the Fc receptors of the murine leukemia L1210.

A glycoprotein extract prepared from the plasma membranes of L1210 cells was passed over columns of Sepharose 4B to which either heat-aggregated human IgG or F(ab')2 fragments has been coupled. The intact IgG column bound 35.7 percent of the applied counts, whereas the F(ab')2 columns bound 2.8 percent. The bound glycoproteins were eluted with citrate buffer (pH 3.2) and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three peaks with apparent molecular weights of 65,000 45,000, and 28,000 daltons were identified and purified by electroelution from polyacrylamide gels. The isolated proteins were able to bind to the same sub-classes of mouse IgG myeloma proteins as the intact L1210 cells, indicating that these molecules are related to L1210 surface Fc receptors. Amino acid analyses of the 3 proteins were markedly similar suggesting that the observed molecular heterogeneity might be due to carbohydrate differences. Neuraminidase digestion of the isolated proteins resulted in mobility shifts on polyacrylamide gel electrophoresis which were consistent with the interpretation that either the isolated proteins have considerably different sialic acid contents, or that removal of the sialic acid results in disaggregation of an Fc receptor molecule.

Animals↗
PubMed1976

Isolation of a murine leukemia FC receptor by selective release induced by surface redistribution.

A protein which binds to the Fc region of IgG has been isolated from the murine leukemia L1210. The isolation technique involves surface cross-linking of the cells's Fc receptors with the use of aggregated human IgG and anti-human IgG. This results in the redistribution (patch formation and capping) of the cells's Fc receptors. Lactoperoxidase-catalyzed radioiodination of the cells before complex binding indicates that Fc receptor redistribution results in the selective release of surface proteins. SDS-PAGE analyses of the supernatants from cells thus treated reveals a major peak corresponding to a molecular weight of 45,000 daltons. This protein has been purified from the cell supernatants by immunoprecipitation and chromatography of the percipitates on Sephadex G-200 under dissociating conditions. After separation from the immune complex this protein can be bound to heat-aggregated IgG, but not aggregated F(ab')2 fragments. The 45,000 dalton protein appears to be the Fc receptor which has been released from the cell surface in association with the complex.

Animals↗
PubMed1975

Reduced antibody-dependent cell-mediated cytotoxicity in systemic lupus erythematosus.

The peripheral blood mononuclear cells from twenty-three patients with SLE were studied. They showed a reduction in antibody-dependent cell-mediated cytotoxicity. This reduction was significantly related to disease activity. No correlations were found with other clinical features. Some of the possible explanations for this finding are discussed.

Adult↗
PubMedDate not supplied

Effect of intra-articular corticosteroids on ligament properties: a biomechanical and histological study in rhesus knees.

The effect of intra-articular corticosteroid injections (methylprednisolone acetate) on the mechanical properties of anterior cruciate bone-ligament-bone units was determined. Fifty-one wild rhesus animals provided 88 knee ligaments units that were loaded in tension to failure under fast strain-rate conditions. Alterations in ligament strength and load-elongation properties were found to depend upon corticosteroid dosage and time after injection. Fifteen weeks after the higher drug dosage (methylprednisolone acetate, 6 mg/kg; three injections, spaced weekly) significant decreases occurred in the maximum failure load (20%), energy absorption prior to failure (11%) and linear stiffness (11%) of the ligament unit. In contrast, only minimal non-significant alterations in ligament strength properties occurred at the higher drug usage after 6 weeks in a second group of animals. this strong time-dependence may partially explain the negative findings reported in short term studies. The higher drug dosage used is approximately 10 times an equivalent human dose on a body mass basis and indicates the ability of this class of drugs to significantly alter the mechanical properties of a ligament unity. A third group of animals received a total of two intra-articular coticosteroid injections (single injections spaced two weeks apart) at a dosage (0.6 mg/kg) equivalent to that commonly used clinically in humans. Statistically significant decreases occurred in maximum failure load (9%) and energy absorption (8%); however, this change is believed of little importance to the projected functional capacity of the ligament unit. No detectable systemic effect of the intra-articular corticosteroid injections was found on the mechanical properties of the ligament unit in the extremity opposite to that which received the drug injection. Histological examination after failure showed normal cellularity and staining characteristics of the ligament, fibrocartilage junction and underlying bone. No bone resorptive changes were observed beneath the ligament insertion site. Failure by a ligamentous mode remained the most common mechanism of specimen failure. Scanning Electron Microscopy showed failure of collagen fibers at multiple levels throughout the ligament indicative of a serial pull-apart failure process. A rich supply of vessels to the anterior cruciate ligament was demonstrated and failure of the vessels occured by a necking down process. Insofar as the results apply to humans, they infer the potential for high and frequent doses of intra-articular slightly soluble corticosteroids to produce alterations in ligament strength and function. A single intra-articular injection or one repeated at intervals of several months probably carries little risk to ligament properties.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Cytotoxicity in progressive systemic sclerosis: no evidence for increased cytotoxicity against fibroblasts of different origin.

Peripheral blood mononuclear cells from 13 patients with progressive systemic sclerosis and 10 normal controls were tested in a cytotoxicity assay against fibroblasts derived from normal adult skin, scleroderma-involved skin and fetal skin. No differences between controls and patients were demonstrated. Sera from patients and controls revealed no differences in cytotoxic effect on scleroderma fibroblast cultures, and patients' sera did not induce antibody-dependent cell-mediated cytotoxicity when added in combination with control peripheral blood mononuclear cells.

Adult↗