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Biomedical subjects

J Chapman

Publications and source records attributed to J Chapman.

At least 307 records · Page 17Linked to original sources
PubMed1992

Calmodulin antagonists chlorpromazine and W-7 inhibit exogenous cholesterol esterification and sphingomyelinase activity in human skin fibroblast cultures. Similarities between drug-induced and Niemann-Pick type C lipidoses.

In this report we showed that calmodulin antagonists chlorpromazine (CPZ) and W-7 (N-[6-aminohexyl]-5-chloro-1-naphtalenesulfonamide), when added to fibroblast cell cultures, gave rise to a time- and dose-dependent decrease of sphingomyelinase activity. CPZ and W-7 also significantly inhibited LDL- and non-LDL-dependent cholesterol esterification. Addition of these drugs to cell culture medium mimicked what is observed in the genetic disease Niemann-Pick type C. H-7 (1-[5-isoquinonylsulfonyl]-2-methylpiperazine), an inhibitor of protein kinase C and cyclic nucleotide-dependent kinases, had no effect on sphingomyelinase and cholesterol ester formation. Thus the possibility of a modulation of cell sphingomyelin and cholesterol esters by a calmodulin-dependent second messenger system must be considered.

Calmodulin↗
PubMed1992

DNA typing: an important step forward? Collaborative Transplant Study.

In a collaborative project which was supported by 96 transplant centers, DNA typing of HLA-DR antigens was carried out on over 7,000 transplant donors and recipients at 8 participating laboratories. Approximately 25% of the individuals were found to have been typed incorrectly by serological means. An analysis of over 2,500 first cadaver kidney transplants showed a significant correlation of matching for the HLA-DR antigens in transplants where the serological typing was confirmed by DNA typing. In transplants where the serological typing was found to be incorrect, the analysis of serological HLA-DR mismatches resulted in no correlation with graft outcome whereas a significant correlation was found when the corrected DNA typed HLA-DR antigens were analyzed. Transplants which had been reported to the Collaborative Transplant Study based on serological typing as matched for HLA-A, -B, -DR or HLA-B, -DR were found to have a superior graft survival rate only if HLA-DR compatibility was confirmed by DNA typing.

DNA Fingerprinting↗
PubMed1992

Firearm deaths in Yorkshire and Humberside.

Firearm fatalities occurring in Yorkshire and Humberside between 1975-1991 were examined; 130 cases were found, 64 were homicides, 55 suicides and 11 were accidental or unclassifiable. All but two of the suicides were men. Shotguns were the most frequent weapon used in both suicides and homicides. Of the 55 suicides, 17 were by men who had murdered before committing suicide. In 15 of these cases the assailants knew their victims. The other two cases involved murder of police officers. These cases were mostly with shotguns. In both homicide and suicide, rifled weapons and handguns were infrequently used. Most suicides and homicides occurred at home. Alcohol was again shown to be a significant factor in suicides. Overall firearms account for less than 10% of homicides in England and Wales and less than 5% of suicides in men and is most unusual in women.

Adolescent↗
PubMed1992

Calcium-calmodulin-dependent activation of adenylate cyclase in prostaglandin-induced electrically-monitored intestinal secretion in the rat.

The calcium-calmodulin antagonist 5-iodo-C8-W7 inhibited the PGE2-induced stimulation of cAMP production by isolated enterocytes from rat small intestine. It also reduced the secretory response of intestinal sheets to PGE2, measured as a rise in short-circuit current. It did not however, inhibit the electrical responses to forskolin and dibutyryl cAMP, nor to acetylcholine, a secretagogue whose effect is not mediated by cAMP. It is concluded that the receptor-mediated activation of adenylate cyclase and the subsequent secretory response are dependent upon calcium-calmodulin.

Acetylcholine↗
PubMed1992

Antibodies from Down's syndrome patients bind to the same cholinergic neurofilament protein recognized by Alzheimer's disease antibodies.

Down's syndrome (DS) patients who survive beyond the third decade develop brain lesions characteristic of Alzheimer's disease (AD). Sera of AD patients contain antibodies that bind specifically to the heavy neurofilament protein (NF-H) of Torpedo cholinergic neurons. In the present report, we examined whether the AD-like pathologic changes in DS are associated with the existence of such antibodies. Our findings show that IgG of older DS patients (greater than 30 years) binds to Torpedo cholinergic NF-H more readily than does that of young DS patients (less than 30 years) and age-matched normal controls. In contrast, the extent of binding of IgG from the young and older DS groups to Torpedo and bovine spinal cords NF-H is similar and equal to that of normal controls. These findings suggest that older DS patients, like AD patients, contain anti-NF-H IgG that binds specifically to epitopes highly enriched in Torpedo cholinergic NF-H.

Adult↗
PubMed1992

Ocular toxicity of subconjunctival gentamicin.

The subconjunctival injection of commercial gentamicin, given either as a single dose or as repeated injections, caused a hyperemic conjunctival response. Simultaneously there was a toxic myopathy induced in the extraocular muscles. The overall response, followed with light microscopy, occurred as a focal infiltrate of polymorphonuclear leukocytes with progression over a few days to a mononuclear cell infiltrate that accompanied fiber degeneration. Injections of each ingredient of commercial gentamicin individually showed that only gentamicin caused the muscle response; methylparaben, EDTA, and sodium bisulfite were without effect. The pH of the solution was eliminated as a contributing factor as was osmolarity of the injection. Increasing recognition is being given to post-operative complications caused by the prophylactic subconjunctival injection of gentamicin following cataract, and other intraocular surgery. The present data offer a mechanistic explanation for many of these toxic findings.

Animals↗
PubMed1991

Induced morphological changes in human small cell lung carcinoma cells.

Several theories suggest that lung carcinomas are not totally separate entities, but are derived from a common precursor, probably of endodermal origin. The histological classification of lung cancers is complex, with much overlap between groups broadly designated as small cell (SCLC), squamous cell, adenocarcinoma and all others simply termed non-small cell. It is shown here that in vitro exposure of classic, non-adherent SCLC lines to 10 microM 5' bromodeoxyuridine (BrdU) results in a rapid cell-line dependent change to a morphology consistent with an adherent, non-small cell phenotype. Accompanying this morphological shift is a decreased expression of the amplified N-myc protooncogene. These induced changes underline the morphological relatedness of lung carcinoma cell lines.

Bromodeoxyuridine↗
PubMed1991

Survival of DNA HLA-DR typed and matched cadaver kidney transplants. The Collaborative Transplant Study.

The clinical value of serological HLA matching for cadaver kidney transplantation remains uncertain because the success rate for HLA-matched cadaver transplants is lower than that of HLA-matched sibling grafts. Up to 25% of serological HLA-DR typings may be incorrect when compared with a more accurate DNA-RFLP method, and we have now examined whether incorrect HLA-DR typings account for the lower than expected success rates of HLA-matched cadaver transplants. 58 transplant centres took part in this study and DNA was extracted from over 4000 samples of frozen tissue at the study centre. 8 laboratories then completed blind RFLP typing for HLA-DR. Serological typing data were reported by individual transplant laboratories. 29 of 107 transplants (27%) that were reported as HLA A, B, DR compatible and 76 of 273 (28%) transplants that were reported as HLA B, DR compatible according to serological typing were found to be HLA-DR mismatched by DNA typing. The one-year transplant success rate for DNA-matched HLA, A, B, DR grafts was 87% compared with 69% for mismatched grafts (p less than 0.02); the corresponding success rate for DNA-matched HLA B, DR grafts was 85% compared with 72% for mismatched grafts (p less than 0.01). Many transplants that were previously thought to be HLA matched are mismatched, and this finding may account for previously unexplained graft failures.

Cadaver↗