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Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 199 records · Page 11Linked to original sources
PubMed1994

Titanium deposition in regional lymph nodes after insertion of titanium screw implants in maxillofacial region.

The deposition of titanium in regional lymph nodes was studied after insertion of endosseous, plasma-spray-coated titanium screw implants in a total of 19 beagle dogs. Five additional animals with no implants served as the control group. After killing the animals 9 months postoperatively, the regional lymph nodes were carefully excised, and samples were prepared for histologic examination. Other samples were used to identify foreign particles by energy-dispersive x-ray analysis and for measurement of the titanium concentration in the tissue by flameless atomic absorption spectroscopy. Very fine foreign-body particles could be seen in the histologic sections, and they were identified as titanium by energy-dispersive x-ray analysis. The atomic absorption analysis for titanium revealed a significantly higher concentration in the group with implants. The presence of very fine, poorly attached particles on the plasma-sprayed titanium surface suggests that these particles may be mechanically dislodged from the surface on insertion of the implants. This suggests that the fine particles may be transported by phagocytes to the regional lymph nodes, where they could be found without any signs of inflammation or foreign-body reaction.

Animals↗
PubMed1994

A graded task approach to the functional mapping of brain areas implicated in auditory-verbal memory.

Positron emission tomography measurements of regional cerebral blood flow (rCBF) were performed in normal volunteers during a graded auditory-verbal memory task. Subjects were required to remember and then immediately, and freely, recall a series of auditorily presented word lists varying from two to 13 words in length. Significant regional correlations between rCBF and memory load (word list length) were identified using statistical parametric mapping. Increasing memory load correlated with increasing rCBF in the cerebellar vermis and hemispheres, thalamus bilaterally, the superior and middle frontal gyri bilaterally, anterior insular regions bilaterally, anterior cingulate, precuneus and left and right lateral premotor areas. Increasing memory load also correlated with decreasing rCBF in the left and right superior temporal/insular regions, medial frontal gyrus, Brodmann's area 37 bilaterally, cuneus, inferior parietal lobule bilaterally and the mid-portion of the cingulate cortex. The pattern of rCBF change closely resembled that identified in a previously reported study using a cognitive subtraction paradigm and provides further evidence for a widespread neural system subserving auditory-verbal memory. The patterns of rCBF response suggest that the areas identified are associated with limited capacity processes for encoding and retrieval.

Adult↗
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↗