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J Simpson

Publications and source records attributed to J Simpson.

At least 181 records · Page 10Linked to original sources
PubMed1993

H7-resistant protein kinase C substrates in two-dimensional gels of proestrous rat anterior pituitary gland.

The presence of Ca(2+)-dependent and -independent protein kinase C (PKC) activities which were stimulated by phorbol-12,13-dibutyrate (PDBu) and sensitive to the kinase inhibitor staurosporine (IC50 values approx. 100 nM) was demonstrated in proestrous rat anterior pituitary gland. These PDBu-induced activities were completely abolished by the PKC-specific inhibitors Ro31-8220 and GF109203X (3 microM). The Ca(2+)-independent activity was more resistant (IC50 = 61 microM) to the kinase inhibitor H7 than the Ca(2+)-dependent activity (IC50 approx. 20 microM), however, this (unusual) resistance to H7 was not observed in the brain regions, hypothalamus and hippocampus. Possible substrates for the Ca(2+)-independent PKC in anterior pituitary were identified by two-dimensional gel electrophoresis and autoradiography following incubation in vitro with [32P]phosphate and 300 nM PDBu +/- 300 nM staurosporine or 30 microM H7. The phosphorylation of six proteins (16, 16, 25, 36, 65 and 69 kDa) was found to be stimulated by PDBu and inhibited by staurosporine, but not H7, in whole tissue, and another two such phosphorylated proteins (each 76 kDa) were observed in microsomal subcellular fractions. These phosphoproteins may be substrates for an H7-resistant PKC isoform previously shown to mediate a number of cellular responses in rat anterior pituitary gland.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Characterisation of protein kinase C isoforms and enzymic activity from the alpha T3-1 gonadotroph-derived cell line.

Western blots of alpha T3-1 cell extracts were immunostained with antibodies specific for various protein kinase C (PKC) isoforms. These revealed the presence of PKC types alpha, epsilon and zeta, but beta, gamma, delta and eta were not detected. The potency with which partially-purified cytosolic PKC from alpha T3-1 cells was activated by phorbol 12,13-dibutyrate (PDBu), mezerein and 1,2-dioctanoyl-sn-glycerol was assessed in the presence and absence of Ca2+. The inhibitors staurosporine, K252a, H7, GF109203X and Ro 31-8220 were tested on basal activity, PDBu-induced activity and Ca(2+) + PDBu-induced kinase activity. Each inhibitor showed distinct differences in their IC50 values under the three conditions, suggesting that these inhibitors may exhibit different potencies on the PKC isoforms present in alpha T3-1 cells. Although histone IIIs was used as the phosphate acceptor for most of these experiments, the efficiency of alpha, epsilon and zeta peptide and GS peptide substrates were also determined, with epsilon peptide giving the greatest activity in the presence of PDBu or Ca2+. Each substrate displayed a different pattern of activation under the conditions tested. Overall, the findings suggest that 3 or more PKC isoforms with varying specificities are present in gonadotroph-derived alpha T3-1 cells and that the contribution of each isoform should be considered when these cells are used in models of anterior pituitary cell function where PKC is involved.

Amino Acid Sequence↗
PubMed1993

Comparison of serum procollagen III peptide concentrations and PGA index for assessment of hepatic fibrosis.

In early hepatic fibrosis, increased amounts of type III collagen are deposited. Persistently high serum concentrations of aminoterminal type III procollagen propeptide (PIIIP) correlate with the activity of the fibrogenic process. Another index for the detection of fibrosis, the PGA index, combines the prothrombin time, gamma-glutamyl transpeptidase activity, and serum apolipoprotein A1 concentration (the latter falls with progressive fibrosis). We compared PIIIP measurements and PGA index in patients with various histological forms of alcoholic liver disease (104), primary biliary cirrhosis (38), and chronic B virus hepatitis (27), and in healthy age-matched controls (30). The ability of each test to identify correctly patients with fibrosis or cirrhosis was assessed with receiver operating curves. The PGA index was much higher in all groups of patients with alcoholic liver disease than in controls (p < 0.0001). PIIIP concentrations were also substantially higher than in controls (p < 0.05 for fatty liver, p < 0.0001 for all other groups), especially in the group with alcoholic hepatitis and cirrhosis. For the detection of cirrhosis the PGA was 91% sensitive and 81% specific and the PIIIP concentration was 94% sensitive and 81% specific. The two tests combined had 85% sensitivity, but 93% specificity. Among patients with primary biliary cirrhosis, both PGA index and PIIIP concentration correlated well with the severity of the disease, determined by the Mayo score (r = 0.72 and 0.66 respectively). The combined tests were 96% sensitive for the detection of fibrosis. All patients with chronic B virus hepatitis had raised PGA and PIIIP values in comparison with controls (p < 0.0001) but there were no differences between subgroups. Substantially raised PIIIP concentrations thus identify the subgroup of alcoholic patients with both hepatitis and cirrhosis. The combination of PGA index and PIIIP concentration may be useful for targeting treatment with antifibrotic drugs and to reduce the need for liver biopsy.

Apolipoprotein A-I↗
PubMed1993

Striatal degeneration induced by mitochondrial blockade is prevented by biologically delivered NGF.

Consistent with the notion that a defect in cellular energy metabolism is a cause of human neurodegenerative disease, systemic treatment with the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NPA) can model the striatal neurodegeneration seen in Huntington's disease. Previously, we have found that nerve growth factor (NGF), delivered biologically by the implantation of a genetically altered fibroblast cell-line, can protect locally against striatal degeneration induced by infusions of high doses of glutamate receptor agonists. We now report that implantation of NGF-secreting fibroblasts reduces the size of adjacent striatal 3-NPA lesions by an average of 64%. We conclude that biologically delivered NGF protects neurons against excitotoxicity and mitochondrial blockade--both energy-depleting processes--implying that appropriate neurotrophic support in the adult brain could protect against neurodegenerative diseases caused in part by energy depletion.

Acetylcholinesterase↗
PubMed1993

Evaluation of canine small intestinal permeability using the lactulose/rhamnose urinary excretion test.

The use of the lactulose and rhamnose urinary excretion test was evaluated in dogs with gastrointestinal disease. Lactulose and rhamnose urinary excretion was measured in three groups of dogs: clinically healthy dogs and dogs with gastrointestinal disease with and without coexistent panhypoproteinaemia. A significant increase in both the percentage of lactulose:percentage of rhamnose urinary excretion ratio and the percentage of lactulose excretion was demonstrated in dogs with hypoproteinaemia when compared to the other two groups. The results suggest that the lactulose/rhamnose urinary excretion test may prove a useful adjunct to currently available tests for assessing small intestinal function, but lacks sensitivity in detecting small intestinal mucosal damage in the absence of villus atrophy.

Animals↗
PubMed1993

Regulation of extracellular fluid volume in neonates.

This review summarises mechanisms of control of extracellular fluid volume in the neonatal period. 'Normal' body fluid distribution and methods of its measurement are discussed as well as regulatory mechanisms with particular emphasis on hormonal and renal aspects.

Animals↗
PubMed1993

Gender and mortality in schizophrenia: do women act like men?

The effect of gender on mortality was explored for a sample of DSM-III diagnosed schizophrenics followed for up to 42 years. The data for 332 cases and 304 matched normal controls were from the retrospective cohort family studies, the Iowa 500 and non-500. Survival analysis and Cox regression models were used to test the effects of gender, illness status and their interaction on the risks for natural and unnatural deaths. The control men experienced significantly more unnatural deaths than the control women, which was not found for schizophrenic men and women. The unnatural death rate among schizophrenic women was similar to the rate for schizophrenic and control men, and significantly higher than for control women during the early phase of the illness. Findings suggest that some factors that predict suicide may be similar for schizophrenic women and men.

Adult↗