Biomedical subjects
Publications and source records attributed to A Doherty.
A series of bi-aryl pyridine carboxylic acids has been prepared and evaluated as inhibitors of ECE-1. The analogs were prepared by Pd catalyzed cross couplings of halogenated pyridines with heteroaryl organo-boranes, -tinate or -zincate derivatives.
Although aneuploidy makes a significant contribution to both somatic and inherited disease the mechanisms by which environmental chemicals may induce numerical chromosome aberrations are only poorly defined. The European Union Project was aimed to further our understanding of those chemical interactions with the components of the mitotic and meiotic cell division cycle which may lead to aneuploidy and to characterise the parameters such as cellular metabolism which may influence the activity of aneugenic chemicals. C-mitosis can be induced by the highly lipophilic polychlorinated biphenyl and the completion of mitosis and cleavage can be modified by agents which deplete cellular levels of reduced glutathione. Modifications of the fidelity of chromosome segregation were produced by inhibiting the functioning of topoisomerase II during chromatid separation. In contrast, the modification of centromere integrity resulted in chromosome breakage as opposed to disturbance of segregation. Modifiers of tubulin assembly and centriolar functioning in somatic cells such as acrylamide, vinblastine and diazepam reproduced their activity in rodent bone marrow and male germ cells. The analysis of chromosome malsegregation in Aspergillus nidulans by a structurally related series of halogenated hydrocarbons was used to develop a QSAR model which had high predictive value for the results of fungal tests for previously untested related chemicals. Metabolic studies of potential aneugens in genetically engineered human lymphoblastoid cells demonstrated the detoxification of the aneugenic activity of chloral hydrate and the activation of 2,3-dichlorobutane, 1,1,2-trichloroethane and trichloroethylene by Phase I biotransforming enzymes. Cell transformation studies in Syrian hamster dermal cultures using a panel of 22 reference and or potential aneugens indicated that 15 of the 22 produced positive results following single exposures. Five of the aneugens which were negative following single exposures produced positive results where cultures were continuously exposed for up to 6 weeks to low concentrations following a single non-transforming exposure to the mutagen dimethyl sulphate. The transformation studies indicate that a significant proportion of chemical aneugens are potential complete carcinogens and/or co-carcinogens. To optimise the enumeration of chromosomes following exposure to potential chemical aneugens whole chromosome paints and centromere specific probes suitable for use in fluorescence in situ hybridisation (FISH) were developed for the rat, mouse and Chinese hamster and selected human probes evaluated for their suitability for routine use. Molecular chromosome probes were used to develop protocols for enumerating chromosomes in metaphase cells and centromeres and micronuclei in interphase cells. The analysis of segregation of specific centromeres in binucleate cells following cytochalasin B treatment was shown to be a potentially valuable system for characterising non-disjunction following chemical exposure. Whole chromosome paints and centromere specific probes were used to demonstrate the presence of dose-response thresholds following treatment with a reference panel of spindle inhibiting chemicals. These data indicate that the FISH technology is suitable for evaluating the relative hazards of low-dose exposures to aneugenic chemicals.
The growth of A. hydrophila on normal pH (5.5-5.8) and high pH ( > 6.0) lamb stored under modified atmospheres was examined. Lamb pieces and mince, inoculated with A. hydrophila were packaged in air, vacuum pack, 80% O2/20% CO2, 50% CO2/50% N2, or 100% CO2 and stored at 5 or 0 degrees C for up to 42 days. Samples were examined for the survival and/or growth of A. hydrophila by enrichment in alkaline peptone water and/or direct plating on starch ampicillin agar. The pH of each sample was estimated. On lamb pieces and mince of normal pH, A. hydrophila numbers decreased during storage at 5 and 0 degrees C under all the packaging conditions. The organism was not detected after 21 days storage. In contrast, A. hydrophila numbers were maintained or increased on high pH lamb under most storage regimes. Storage at 5 degrees C allowed significant increases in A. hydrophila numbers on high pH lamb under all the atmospheres, except 100% CO2. In lamb held at 5 degrees C under 100% CO2 for up to 42 days, A. hydrophila was recovered from most samples, although cell numbers decreased during storage. After storage at 0 degrees C, A. hydrophila was recovered from high pH packs stored under all atmospheres. Significant increases in cell numbers were only observed in minced lamb of high pH stored under air or vacuum. The pH values of lamb pieces and mince held at 5 or 0 degrees C under any of the packaging atmospheres did not change in a uniform manner during storage.
We report on the psychosocial and substance use profiles of the 55 "Area Boys and Girls" (ABG) admitted to a Rehabilitation Camp in Lagos between March and May 1993 under the main auspices of the People's Bank of Nigeria. The majority were males (73%); young adults (mean age/SD: 30.6/6.3); unemployed (73%); not married (80%); of low educational standing (87%) and from low socio-economic background (over 70%). Almost all were current users of heroin (89%) and cocaine (87%), procured with a substantial amount of money and administered mainly through smoking and "chasing the dragon". None of the clients reported injecting the drug. These findings have highlighted the intricate nature of the problems of ABG and the need for a comprehensive rehabilitation package encompassing general medical, psychological and psychiatric care. Such programmes, ideally free, should be a joint venture between the government, international agencies, non-governmental organizations and the community as a whole. The key emphasis should be on equipping the clients with occupational skills for life-long economic sustenance. To curtail the growing numbers of displaced young people in the country, the government should give due attention to the root causes of the multiple social ills in the society.
The MCL-5 cell line is a human lymphoblastoid TK+/- cell line that constitutively expresses a relatively high level of native CYP1A1, four other human cytochromes (CYP1A2, CYP2A6, CYP3A4 and CYP2E1) and microsomal epoxide hydrolase, carried as cDNAs in plasmids. The aim of this study was to evaluate this cell line for its suitability for detecting chromosomal anomalies, employing micronucleus formation in cells blocked at cytokinesis as the indicator of clastogenicity. Results from two laboratories ('ICR' and 'Swansea') using different protocols are reported. In the ICR protocol, aflatoxin B1, sterigmatocystin, benzo[a]pyrene, dibenz[a,h]anthracene, 3-methylcholanthrene, cyclophosphamide, N-nitrosodimethylamine, 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline, benzidine, 2-aminofluorene, benzene, tamoxifen and omeprazole were tested and gave positive results. Anthracene, phenanthrene and pyrene were negative. In the Swansea protocol, AHH-1 cells, the parent line which constitutively expresses CYP1A1, but does not contain the genetically engineered human cytochromes or epoxide hydrolase, were tested in parallel with MCL-5 cells. Aflatoxin B1, sterigmatocystin, benzo[a]pyrene, N-nitrosodiethylamine, 2-acetylaminofluorene, benzene, omeprazole and tamoxifen were tested and gave positive results. Of these, only benzo[a]pyrene was equally potent in both cell lines. Assays of tamoxifen and omeprazole included kinetochore staining. Omeprazole, but not tamoxifen, induced a significant level of kinetochore-positive micronuclei. The detection of micronucleus formation in these genetically engineered cells appears to be a rapid, eclectic and sensitive method for screening for genotoxic activity in vitro.
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The rudimentary right ventricle in hearts with double inlet to a dominant left ventricle can exist either to the right or the left side of the ventricular mass. These variants have been interpreted to imply differences in ventricular topology. If correct, they also imply that differences should exist in the morphology of the atrioventricular valves, previously thought to be indistinguishable one from the other. To test this possibility, we examined 15 hearts with double inlet to a morphologically left ventricle and 10 normal hearts. The distinguishing features of normal valves were evaluated for their consistency, and the most reliable were employed for interpreting the valves in the abnormal hearts. As shown by previous echocardiographic studies, insertion of valvar tension apparatus to the interventricular septum was unique to the morphologically tricuspid valve. Ten of the abnormal hearts had one valve showing this feature, it being absent in the other valve. The attachment, consistently on the same side as the rudimentary right ventricle, could be of diagnostic value in determining ventricular topology. In our small study, nonetheless, this approach still leaves one third of the hearts in which topology cannot be ascertained with certainty and in which it is not possible to distinguish the morphological nature of the atrioventricular valves.
Elective dental care could be rendered to AIDS patients without posing any health danger to both the dental personnel and the other patients if appropriate protocols are followed to prevent cross-contamination. Elective dental service was provided to an AIDS patient under sterile-clean technique. It should be emphasized that this paper is not on AIDS but about the elective dental management of an AIDS patient using sterile-draping technique
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The proton-translocating subunit of wheat chloroplast ATP synthase is encoded by a chloroplast gene that has been accurately mapped and whose nucleotide sequence has been determined. The predicted sequence of 81 amino acids has been confirmed in part by determination of the sequence of the first 40 amino acids from the NH(2) terminus of the protein, and it shows 100% homology with the known amino acid sequence of the spinach protein but no more than 35% homology with the amino acid sequences of bacterial and mitochondrial proteins. The gene shows no deviation from the "universal" genetic code and is not split. A potential ribosome binding site is located 12 nucleotides upstream from the initiation codon, but sequences homologous to prokaryotic promotors and transcription terminators are not apparent.
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Chloroplasts, isolated from the leaves of 7-day-old pea seedlings, were incubated in the light with [35S]methionine or [3H]leucine. After extraction from the washed chloroplast membranes using a mixture of ethyl acetate, ethanol and ammonia, cytochrome f was precipitated with a monospecific antiserum and resolved by gradient polyacrylamide gel electrophoresis in sodium dodecylsulphate. The cytochrome f band was identified by its intrinsic fluorescence in ultraviolet light and was shown to be radioactive by autoradiography or fluorography of dried polyacrylamide gel. One-dimensional peptide mapping of the products of papain hydrolysis confirmed that the radioactivity was an integral part of cytochrome f. The incorporation of [35S]methionine into cytochrome f was inhibited by D(-)threo-chloramphenicol but not by cycloheximide and did not occur in the dark. The synthesis was resistant to ribonuclease. It is concluded that cytochrome f is synthesised in intact isolated pea chloroplasts.
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