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Biomedical subjects

A Bennett

Publications and source records attributed to A Bennett.

At least 145 records · Page 8Linked to original sources
PubMed1987

Platelet hyperaggregability in the nephrotic syndrome which is not dependent on arachidonic acid metabolism or on plasma albumin concentration.

In 20 patients with nephrotic syndrome we confirm previous findings of in vitro platelet hyperaggregability to arachidonic acid, and describe similar hyperaggregability to ristocetin. As previously reported also, the addition of albumin to nephrotic platelet-rich plasmas corrected platelet hyperaggregability to arachidonic acid, but exerted little effect on ristocetin-induced aggregation, and there was no correlation between platelet aggregation thresholds to arachidonate and to ristocetin. Incubation with indomethacin abolished the generation of thromboxane B2 after stimulation with arachidonate, but had no effect on the stimulation with ristocetin, during which no TxB2 was produced. The nephrotic patients had elevated factor VIII-related antigen (Factor VIII R:Ag) concentrations in their plasma, but in addition both decreased serum IgG and platelet-associated IgG were found which were correlated. The hyperaggregability of nephrotic platelets to ristocetin may relate to the elevated factor VIII R:Ag levels, or to the low platelet-associated IgG, since platelet IgG Fc receptors and von Willebrand factor receptors are spatially close or identical.

Adult↗
PubMed1986

Survival of mice with NC carcinoma is unchanged by drugs that are thought to inhibit thromboxane synthesis or increase prostacyclin formation.

Mice transplanted with NC carcinoma were treated with the thromboxane synthetase inhibitor dazmegrel (UK38485) or with nafazatrom (BAY G 6575), a compound that is reported to increase prostacyclin formation. Some experiments included the cytotoxic drugs methotrexate and melphalan. The tumours were excised under anaesthesia on day 14 or day 21 after transplantation, and weighed; some were extracted for prostanoids which were measured by radioimmunoassay. Mouse survival time was determined up to day 121, and cancer spread was determined by postmortem examination. The survival was increased by methotrexate and melphalan but not by the other drugs. Nafazatrom-treated mice tended to have lighter tumours. Although dazmegrel reduced the formation of thromboxane B2 during clotting of blood from normal mice, it did not affect the tumour yields of prostanoids. Nafazatrom had no effect on serum or tumour prostanoids. There were no obvious effects of the treatments on the recurrence of tumour in the excision scar, lung metastasis or spread to lymph nodes.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

DNase I-hypersensitive sites in the 5'-flanking region of the rat serum albumin gene: correlation between chromatin structure and transcriptional activity.

As tested by DNase I digestion, the chromatin structure in several regions 5' to the rat serum albumin gene varies in tissues and cell lines that differ in transcription rate of this gene. Three DNase I-hypersensitive regions were found in hepatocyte nuclei but not in kidney cell nuclei. The sites were approximately 2.8 kbp (site 1), 0.2 kbp (site 2), and 0.05 kbp (site 3) upstream from the cap site of the gene. In rat fetal liver tissue and rat hepatoma cell lines (FaO, C2, and C2-rev7), as well as in cultured primary hepatocytes where the rate of albumin gene transcription is lower than in adult liver, hypersensitive site (HSS) 1 was absent while sites 2 and 3 were present. In addition, the C2 cell line, which does not express albumin mRNA, contains a different HSS at position -1.5 kbp. Factors (proteins) bound to sites 2 and 3 may allow cell-specific transcription, but the additional factor interaction at site 1 could be required for a maximal rate of albumin gene transcription.

Animals↗
PubMed1986

Influence of ketanserin pretreatment on the haemodynamic responses to sternotomy.

The effect of intravenous ketanserin on the pressor response to sternotomy was studied in 36 patients undergoing coronary artery surgery. Two doses of the drug (10 mg and 20 mg) were compared with a placebo injection of saline. After induction of anaesthesia, haemodynamic variables were measured until the institution of cardiopulmonary bypass. Plasma and platelet 5-hydroxyindoles and 5-hydroxytryptamine were measured in a subset of 13 patients. Ketanserin induced a dose-dependent amelioration of the pressor response to sternotomy. Plasma 5-hydroxyindoles and platelet 5-hydroxytryptamine levels did not correlate with clinical response. The increased effectiveness of the higher dose of ketanserin may be due to an effect other than serotonin antagonism.

Drug Evaluation↗
PubMed1986

Platelet-associated IgG in idiopathic glomerulonephritis and the nephritis of systemic lupus erythematosus.

We studied platelet-associated IgG (PAIgG) in patients with the nephritis of systemic lupus erythematosus (SLE) and with idiopathic glomerulonephritis (IGN), and found no increase in PAIgG in the patients with IGN, and an increase in only a minority of patients with SLE, all of whom had active disease. Patients with IGN and a nephrotic syndrome had both a low serum IgG and a low PAIgG. The increase in PAIgG in the patients with SLE correlated with the titres of antibody against dsDNA in the serum, but not with the platelet-agglutinating immune complexes also present. Intraplatelet serotonin, however, was reduced in both groups, and this correlated with the amounts of platelet-agglutinating complexes in the serum of the SLE patients. Immune complexes may associate with platelets in vivo to cause this release, but if so this must be a reversible phenomenon ('hit and run' immune platelet injury); alternatively, the Fc binding to the platelet surface may be weak and insufficient to survive the ex vivo washing procedures.

Blood Platelets↗
PubMed1986

Presence of endothelial cell growth factor activity in normal and diabetic eyes.

Two classes of growth factors affecting endothelial cell proliferation have been found previously in ocular tissues: a heat labile mitogen from retina (RDGF) and a heat stable inhibitor of proliferation from vitreous. The relative amounts of these growth factors in normal and diabetic cadaver eyes were investigated using fetal bovine aortic endothelial cell proliferation as an assay. Equivalent levels of RDGF activity were extracted from diabetic and normal sensory retinas. An extract from pigment epithelium and choroid was found to have similar levels of mitogenic activity, but this activity was not as heat labile as RDGF. Like RDGF, equivalent amounts of mitogen were extracted from diabetic and normal tissue. Normal human vitreous inhibited endothelial cell proliferation, and this activity was enhanced by heating the material (10 min., 95 degrees C). Four of the five individual diabetic vitreous samples of identical postmortem times were mitogenic when not heated, and exhibited little or no inhibitory activity when heated. Vitreous of identical postmortem times was pooled and fractionated by heparin-Sepharose chromatography to determine if the heat labile mitogen in vitreous was RDGF. From the insulin-dependent diabetic (IDDM) pooled vitreous sample, a prominent protein of 18 Kd was eluted from the column with 1.2 M NaC1, a characteristic of RDGF. This work suggests that both RDGF and the vitreous inhibitor are found in human vitreous, but their relative concentrations may change in the diabetic state so that retinal neovascularization from retina can occur.

Animals↗
PubMed1986

Platelet-associated DNA and anti-DNA antibody in systemic lupus erythematosus with nephritis.

We report DNA and specific anti-dsDNA antibody (dsDNAb) in excess of controls, associated with platelets from 35 patients with systemic lupus erythematosus (SLE). Deoxyribonuclease (DNase) treatment of intact platelets resulted not only in a drop in platelet-associated DNA, but also a dramatic fall in platelet-associated dsDNAb. This suggests that at least some DNA and virtually all the dsDNAb is bound to the platelet surface, probably in the form of an immune complex. The quantity of platelet-associated DNA did not correlate with amounts of platelet-associated anti-dsDNA antibody (PAdsDNAb); perhaps because platelets also have receptors for DNA itself. Total platelet-associated IgG was elevated in only six patients with normal PAdsDNab.

Antibodies, Antinuclear↗
PubMed1985

The role of calcium in eicosanoid production induced by ricinoleic acid or the calcium ionophore A23187.

Rat isolated intestine incubated in Krebs solution converted exogenous [14C]-arachidonic acid into products that chromatographed with prostaglandins, leukotriene B4 and 5-hydroxy-eicosatetraenoic acid. Accumulation of these products was increased by the laxative ricinoleic acid (0.34 mM) or the calcium ionophore A23187 (7.6 microM). In the presence of the calcium antagonists TMB-8 (0.43 microM) or verapamil (0.2 microM) the mean effects of ricinoleic acid or the calcium ionophore were smaller. Stimulation of arachidonic acid metabolism by ricinoleic acid therefore seems likely to involve a calcium-dependent mechanism.

Animals↗
PubMed1985

Treatment of mouse carcinoma in vivo with a prostaglandin E2 analogue and indomethacin.

WHT/Ht mice transplanted s.c. with NC carcinoma were treated with 16,16-dimethyl prostaglandin E2 methyl ester (di-me-PGE2) and/or indomethacin. Each primary tumour was excised under anaesthesia 3 weeks after transplantation, weighed and extracted for prostaglandins. Mouse survival time and tumour recurrence were measured. Di-me-PGE2 10 micrograms, injected at the tumour site on alternate days from day 1 to 19, indomethacin 2.5 mg kg-1 daily by mouth, or both drugs together resulted in lighter tumours (respectively 45, 45 and 52% less, n = 18 to 20 per group, P less than 0.02) compared with vehicle-treated controls. Indomethacin reduced the tumour prostaglandin yield, but the biological activity in extracts of tumours from mice given di-me-PGE2 was high. The median survival time was longer in mice receiving indomethacin alone (61 days from tumour transplantation compared with 50 days in controls P less than 0.02). Di-me-PGE2 alone had little or no effect on survival (median 48 days) but counteracted the increase with indomethacin (di-me-PGE2 + indomethacin, 49 days median survival). There were no obvious effects of the treatments on tumour recurrence at the excision site, but there was a higher incidence of involved lymph nodes in mice given di-me-PGE2.

16,16-Dimethylprostaglandin E2↗
PubMed1985

Carbenoxolone and deglycyrrhized liquorice have little or no effect on prostanoid synthesis by rat gastric mucosa ex vivo.

Rats were given either carbenoxolone 50 mg kg-1, deglycyrrhized liquorice 1 g kg-1 or vehicle by gastric tube. The doses were repeated 16 h later, and the stomachs removed after another 2 h. The amounts of prostaglandin E (PGE), 6-keto-PGF1 alpha and thromboxane B2, measured by radioimmunoassay in extracts of the gastric corpus and antrum mucosa, were similar in the treated animals and the controls. We conclude that in rats, carbenoxolone and deglycyrrhized liquorice may exert their anti-ulcer effect by a non-prostaglandin mechanism. This contrasts with the mechanism through to occur in man with carbenoxolone.

6-Ketoprostaglandin F1 alpha↗