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Biomedical subjects

S M Cooper

Publications and source records attributed to S M Cooper.

At least 109 records · Page 6Linked to original sources

Prevention of type II collagen-induced arthritis by in vivo treatment with anti-L3T4.

The effect of in vivo administration of monoclonal anti-L3T4 antibody on the development of murine collagen-induced arthritis (CIA) was assessed. Treatment with anti-L3T4 resulted in a greater than 90% depletion of L3T4+ T cells in lymph nodes and spleen, an effect that appears entirely reversed 30 d after treatment. Administration of anti-L3T4 before immunization with type II collagen resulted in a significant decrease in arthritis incidence and delayed onset of the disease while treatment begun after a strong anticollagen IgG humoral response was underway was not effective in altering disease expression. These results suggest a prominent role for L3T4+ T cells in the pathogenesis of CIA.

Animals↗

Role of dopamine and alpha-adrenoreceptors in the control of gastric emptying in the rat: possible involvement in the mechanism of action of metoclopramide.

The object of the study was to investigate the effects of dopamine receptor and alpha-adrenoreceptor agonists and antagonists on the gastric emptying of a liquid test meal in conscious rats and the possible involvement of these receptors in the mechanism of action of metoclopramide. The gastric emptying of a liquid test meal in conscious chronic gastric fistula rats was delayed following subcutaneous administration of either 6,7-ADTN (1-50 mg/kg) or clonidine (0.05-1 mg/kg). Phenylephrine (0.2-10 mg/kg s.c.) had no effect on gastric emptying, suggesting that dopamine and alpha 2-, but not alpha 1-adrenoreceptors may be involved in the control of gastric emptying in the rat. Phentolamine (0.2-5 mg/kg s.c.) and prazosin (0.1-0.5 mg/kg s.c.) potentiated the delay in gastric emptying induced by 6,7-ADTN, whilst yohimbine (1-5 mg/kg s.c.) and prazosin (0.1-0.5 mg/kg s.c.) reversed the delay in emptying induced by clonidine. All three alpha-adrenoreceptor antagonists also delayed gastric emptying in the absence of agonist. Propranolol (0.2-5 mg/kg s.c.) had no effect on either normal or delayed gastric emptying. Both metoclopramide (1-10 mg/kg s.c.) and haloperidol (0.02-0.5 mg/kg s.c.) reversed the 6,7-ADTN-induced delayed emptying but not the clonidine-induced delayed emptying. In addition, metoclopramide (5-10 mg/kg s.c.), but not haloperidol, increased gastric emptying in the absence of agonist. In conclusion, these results show that dopamine and alpha-adrenoreceptors may be involved in the control of gastric emptying in the rat. However, it would appear that alpha 2-adrenoreceptors are unlikely to be involved in the mechanism of action of metoclopramide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Post tonsillectomy haemorrhage.

In a review of 3,756 cases of tonsillectomy the incidence of reactionary and secondary haemorrhage was the same-1 per cent. Both types of haemorrhage were commoner in adults. In the 10-19 age group, significantly more females than males had secondary bleeding. Although the majority occurred during the winter months, no patient with secondary haemorrhage had obvious respiratory tract infection. The use of diathermy at operation, while associated with a higher rate of secondary bleeding, significantly reduced the number of reactionary haemorrhages which are responsible for a high proportion of post-tonsillectomy fatalities.

Adolescent↗

Fc receptors of mouse cell lines. I. Distinct proteins mediate the IgG subclass-specific Fc binding activities of macrophages.

To determine the biochemical basis for the two distinct IgG subclass binding specificities on mouse macrophage-like cell lines, Fc-binding proteins were isolated from P388D1 and J774 cells by affinity chromatography using immobilized IgG. Similar IgG subclass-specific Fc gamma-binding proteins were identified on both cell lines. The Fc-binding proteins were characterized by their IgG subclass binding specificity, size, charge, and trypsin sensitivity. Using immobilized IgG1, a protein was isolated with an average m.w. of 65,000 and a pI range of pH 4.7 to 5.8. This protein could also be isolated, although in reduced amounts, with immobilized IgG2b. Two proteins with average m.w. of 70,000 and 60,000 and a pI range of 3.8 to 4.7 were isolated with immobilized IgG2a. The 60-kd protein appeared to be derived from the 70-kd protein. The IgG1/IgG2b Fc-binding proteins were resistant to trypsin, whereas the IgG2a Fc-binding proteins were sensitive to trypsin. In IgG-binding studies with the isolated proteins, the IgG2a Fc-binding proteins continued to exhibit restricted binding specificity for the IgG2a subclass; however, the IgG1/IgG2b Fc-binding proteins showed a broader specificity and would rebind to IgG1, IgG2a, and IgG2b. The IgG-binding properties and trypsin sensitivity of these Fc-binding proteins were similar to the properties of the IgG binding sites on the intact cells. These data indicate that the IgG subclass-specific binding sites on macrophage-like cell lines are due to the presence of distinct protein molecules on the cell surface.

Animals↗

The effect of lead upon urate nucleation.

Lead urate was crystallized from solutions originally containing 0.595 mM (10 mg%) urate and 0.297 mM PbCl2. In the absence of lead, monosodium urate does not nucleate unless the urate concentration exceeds 80 mg%. Lead urate crystals were negatively birefringent and had a distinct x-ray powder diffraction pattern. Crystals of monosodium urate nucleated on lead urate seed crystals when the urate concentration was 10 mg%. These studies indicate that with physiologic conditions of temperature, pH, and ionic strength, spontaneous nucleation of lead urate can be demonstrated.

Chemical Phenomena↗

Structural evidence for distinct IgG subclass-specific Fc receptors on mouse peritoneal macrophages.

Membrane proteins which selectively bind to the Fc portion of IgG were identified in the Nonidet P-40 extracts of radiolabeled thioglycollate- elicited mouse peritoneal macrophages. Affinity columns of various IgG preparations coupled to Sepharose 4B were used to absorb the Fc-binding proteins. Analysis of the acetic acid or sodium dodecyl sulfate (SDS) eluates from aggregated human IgG or antigen-complexed rabbit IgG columns revealed two Fc(gamma)/-specific proteins with apparent 67,000 and 52,000 mol wt. These proteins were not detected in acid or SDS eluates from F(ab')(2) columns or in eluates from IgG column, over which were passed lysates of Fc receptor-negative cells. With the use of affinity columns that contained aggregated mouse myeloma proteins of different IgG subclasses, we found that the 67,000-dahon protein selectively binds to IgG2a, whereas the 52,000-dalton protein binds to IgG1 and IgG2b. Neither protein was found in SDS eluates from IgG3 columns. Trypsin treatment of the macrophages before detergent lysis removed the 67,000-dalton protein, although it leaves intact the 52,000-dalton protein. These results provide structural confirmation for the existence of separate Fc receptors on mouse macrophages and indicate that the two Fc-binding proteins identified in this study represent all or part of the trypsin- sensitive Fc receptor which binds IgG2a and the trypsin-resistant Fc receptor which binds IgG2b and IgG1.

Animals↗

Fatty acid specificities of microsomal acyltransferases esterifying positions-1 and -2 of acylglycerols in mammary glands from lactating rats.

The acyl specificities of several acyltransferases located in the microsomal fraction of lactating rat mammary gland have been investigated using palmitate and oleate as substrates along with CoA, ATP and Mg(2+), bovine serum albumin and NaF. With either sn-glycerol 3-phosphate or dihydroxyacetone phosphate (plus NADPH) as acyl acceptor, phosphatidic acid containing palmitate preferentially esterified at position-2 and oleate at position-1 was the major product. Dihydroxyacetone phosphate and sn-glycerol 3-phosphate competitively inhibited each other's acylations, suggesting that a single enzyme might be responsible for both esterifications and oleate was the preferred substrate for the formation of acyldihydroxyacetone phosphate. The specificities of the acyl-CoA-1-monoacyl-sn-glycerol 3-phosphate and the acyl-CoA-2-monoacyl-sn-glycerol 3-phosphate acyltransferases were also studied. The specificities observed combined with the relative velocities of these reactions suggest that phosphatidic acid is formed in the mammary gland with the first acylation occurring at position-1 favouring oleate followed by the second acylation at position-2 favouring palmitate. This is consistent with the unusual structure found in the triacylglycerols of rat milk. When a mouse liver microsomal fraction was used the opposite specificities were observed consistent with the structure of the triacylglycerols of mouse liver. The microsomal acylation of the monoacyl-sn-glycerol 3-phosphocholines was also investigated. Although no marked acyl specificity could be detected when the 2-monoacyl-sn-glycerol 3-phosphocholine was used as the acyl acceptor, both oleate and linoleate were esterified in preference to palmitate to the 1-monoacyl-sn-glycerol 3-phosphocholine.

Acylation↗

Studies on the nucleation of monosodium urate at 37 degrees c.

Factors influencing the nucleation of monosodium urate (NaHU) were studied with supersaturated solutions of sodium urate at physiologic conditions of temperature, pH, and ionic strength. Spontaneous nucleation of NaHU did not occur at urate concentrations of 5 mM (84 mg%) in the presence of 140 mM Na ion. Addition of synovial fluids from gout patients greatly enhanced nucleation, whereas fluids from degenerative joint disease patients moderately enhanced nucleation, and fluids from rheumatoid arthritis patients had only a slight effect. Hyaluronic acid and purines minimally enhanced urate crystallization, whereas other connective tissue components had no effect.

Connective Tissue↗

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↗

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↗

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↗

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↗