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Biomedical subjects

M Griffin

Publications and source records attributed to M Griffin.

At least 127 records · Page 7Linked to original sources
PubMed1998

Mixed psychosocial outcomes of sisters from families with alcoholic parents.

To examine intrafamilial differences in adulthood among children of alcoholic parents, 14 women with alcoholic parents and their sisters were assessed for this exploratory study. Reported here is the subset of eight "mixed" sister pairs, one with an impaired adult outcome and the other with a well-adjusted adult outcome. Subjects who scored significantly worse than community norms on depressed mood or social supports or who had a psychiatric diagnosis including substance abuse were categorized as impaired, while the remaining women were categorized as well-adjusted. Both qualitative and quantitative data were collected using a questionnaire and a structured interview. Results showed similarities between the impaired and well-adjusted sisters on individual characteristics, with few differences on characteristics of the parental alcoholism. The most marked differences showed the impaired sisters to score worse than their well-adjusted sisters on characteristics of the home environment and social supports. The impaired women were also more likely to have been physically abused in childhood and to rate the effect of having an alcoholic parent as more negative than the well-adjusted women. Unanticipated findings relating to incest, talents, denial, and racial differences, and their implications for clinicians and researchers, are discussed.

Adolescent↗
PubMed1998

The effect of B-mode ultrasonic image standardisation on the echodensity of symptomatic and asymptomatic carotid bifurcation plaques.

BACKGROUND: To develop a method that allows B-mode ultrasonic images of carotid plaques to be standardised so that measurements of plaque echodensity become comparable and clinically useful. METHODS: Design. Cross sectional study. Setting. Teaching hospital, England. PATIENTS: a random consecutive series of 23 patients in part I, 19 in part II and 77 in part III. Measures. Part I: twenty-three images of carotid bifurcation plaques from 2 duplex scanners were digitised. Images were standardised by 4 observers so that the grey scale median (GSM) would be 0-5 for blood and 185-195 for adventitia. Part II: the effect of three different recording media: video, magneto-optical disk (MOD) and thermal paper on the echodensity of 19 plaques' images was determined. Part III: the echodensity of 91 carotid bifurcation plaques with greater than 50% stenosis was correlated to the presence or absence of ipsilateral hemispherical symptoms. RESULTS: Part I: the coefficient of variation (CV) among 4 observers was 0.7%, 0% and 4.7% after image standardisation for the adventitia, blood and plaques respectively. Part II: a near perfect agreement was obtained between the GSM of plaques from images on video and MOD (r = 0.97) after standardisation. Part III: after standardisation, the GSM of symptomatic plaques was lower (21 +/- 14.8) than in asymptomatic plaques (38 +/- 26) p = 0.002. Plaque echolucency was more likely to be associated with symptoms (relative risk 4.1 90% CI 1.8-9.4). CONCLUSIONS: Images from different scanners by different ultrasonographers and through different peripherals can be standardised so that measurements of plaque echodensity may become comparable. The method is recommended for use in future natural history studies on carotid plaques where stroke is the end-point.

Carotid Artery Thrombosis↗
PubMed1997

External supply of oxygen to the atmospheres of the giant planets.

The atmospheres of the giant planets are reducing, being mainly composed of hydrogen, helium and methane. But the rings and icy satellites that surround these planets, together with the flux of interplanetary dust, could act as important sources of oxygen, which would be delivered to the atmospheres mainly in the form of water ice or silicate dust. Here we report the detection, by infrared spectroscopy, of gaseous H2O in the upper atmospheres of Saturn, Uranus and Neptune. The implied H2O column densities are 1.5 x 10(15), 9 x 10(13) and 3 x 10(14) molecules cm(-2) respectively. CO2 in comparable amounts was also detected in the atmospheres of Saturn and Neptune. These observations can be accounted for by external fluxes of 10(5)-10(7) H2O molecules cm(-2) s(-1) and subsequent chemical processing in the atmospheres. The presence of gaseous water and infalling dust will affect the photochemistry, energy budget and ionospheric properties of these atmospheres. Moreover, our findings may help to constrain the injection rate and possible activity of distant icy objects in the Solar System.

Carbon Dioxide↗
PubMed1997

The role of transglutaminase in the rat subtotal nephrectomy model of renal fibrosis.

Tissue transglutaminase is a calcium-dependent enzyme that catalyzes the cross-linking of polypeptide chains, including those of extracellular matrix (ECM) proteins, through the formation of epsilon-(gamma-glutamyl) lysine bonds. This crosslinking leads to the formation of protein polymers that are highly resistant to degradation. As a consequence, the enzyme has been implicated in the deposition of ECM protein in fibrotic diseases such as pulmonary fibrosis and atherosclerosis. In this study, we have investigated the involvement of tissue transglutaminase in the development of kidney fibrosis in adult male Wistar rats submitted to subtotal nephrectomy (SNx). Groups of six rats were killed on days 7, 30, 90, and 120 after SNx. As previously described, these rats developed progressive glomerulosclerosis and tubulo-interstitial fibrosis. The tissue level of epsilon-(gamma-glutamyl) lysine cross-link (as determined by exhaustive proteolytic digestion followed by cation exchange chromatography) increased from 3.47+/- 0.94 (mean+/-SEM) in controls to 13.24+/-1.43 nmol/g protein 90 d after SNx, P </= 0.01. Levels of epsilon-(gamma-glutamyl) lysine cross-link correlated well with the renal fibrosis score throughout the 120 observation days (r = 0.78, P </= 0.01). Tissue homogenates showed no significant change in overall transglutaminase activity (14C putrescine incorporation assay) unless adjusted for the loss of viable tubule cells, when an increase from 5.77+/-0.35 to 13.93+/-4.21 U/mg DNA in cytosolic tissue transglutaminase activity was seen. This increase was supported by Western blot analysis, showing a parallel increase in renal tissue transglutaminase content. Immunohistochemistry demonstrated that this large increase in epsilon-(gamma-glutamyl) lysine cross-link and tissue transglutaminase took place predominantly in the cytoplasm of tubular cells, while immunofluorescence also showed low levels of the epsilon-(gamma-glutamyl) lysine cross-link in the extracellular renal interstitial space. The number of cells showing increases in tissue transglutaminase and its cross-link product, epsilon-(gamma-glutamyl) lysine appeared greater than those showing signs of typical apoptosis as determined by in situ end-labeling. This observed association between tissue transglutaminase, epsilon-(gamma-glutamyl) lysine cross-link, and renal tubulointerstitial scarring in rats submitted to SNx suggests that tissue transglutaminase may play an important role in the development of experimental renal fibrosis and the associated loss of tubule integrity.

Animals↗
PubMed1997

Assays for the measurement of tissue transglutaminase (type II) mediated protein crosslinking via epsilon-(gamma-glutamyl) lysine and N',N'-bis (gamma-glutamyl) polyamine linkages using biotin labelled casein.

Two colorimetric assays for tissue transglutaminase (type II) activity involving the crosslinking of proteins have been developed. In one assay, biotin labelled casein is crosslinked into chemically modified casein bound to a microtiter plate by tissue transglutaminase and the biotin labelled reaction product is detected by conjugation to Extravidin peroxidase. The assay can detect activity in 10 ng of commercially available purified guinea pig liver transglutaminase and in the crude homogenate derived from 400 human endothelial cells (cell line ECV 304). A correlation (r2 = 0.977) was shown between this assay and the radiolabeled putrescine incorporation assay for the detection of transglutaminase activity. This assay measures the protein crosslinking activity of tissue transglutaminase as opposed to polyamine incorporation and offers a rapid, non-radiometric method for screening large sample numbers. Typical inter-assay variability is 13.9 +/- 1.5% (n = 8). In a second assay, the ability of tissue transglutaminase to catalyze the formation of N',N'-bis (gamma-glutamyl) polyamine bridges is measured. N',N'-dimethylcasein is bound to a microtiter plate and modified enzymatically using commercially available purified guinea pig liver transglutaminase to incorporate polyamines into glutamine residues. Biotin labelled casein is then crosslinked into the immobilized polyamines by tissue transglutaminase resulting in the formation of N',N'-bis (gamma-glutamyl) polyamine linkages.

Animals↗
PubMed1997

The secretory epithelial cells of the choroid plexus employ a novel kinesin-related protein.

The proteins of the kinesin superfamily (KIFs) are microtubule-based molecular motors whose functions include the transport of membrane-bound organelles. We have isolated the cDNA encoding a novel kinesin by reverse transcription and polymerase chain reaction using degenerate primers that flank the highly conserved motor domain. The deduced amino acid sequence of this protein shows considerable similarity to both KIF1A and KIF1B thus defining it as a new member of the monomeric KIF1/unc104 family. The C-terminal domain of KIF1D is the most divergent by comparison with the other members of the family, which supports the view that the tail region is responsible for conferring specificity on the interactions of these kinesins with their cargoes. In the adult rat brain KIF1D mRNA is expressed in neurons in the hippocampus and in the Purkinje cells of the cerebellum. However, the levels of KIF1D are particularly high in the choroid plexus which is a polarised epithelium that lines the lateral, third and fourth ventricles. The major function of the epithelial cells in the choroid plexus is to produce cerebrospinal fluid, which suggests that KIF1D plays an important role in their secretory function.

Amino Acid Sequence↗
PubMed1997

The cell cycle and induction of apoptosis in a hamster fibrosarcoma cell line treated with anti-cancer drugs: its importance to solid tumour chemotherapy.

The induction of apoptosis by anticancer drugs and its relationship to stages of the cell cycle was studied in cells derived from a solid tumour; a highly malignant hamster fibrosarcoma (Met B). Asynchronously proliferating cells were treated with a wide variety of agents such as actinomycin-D, 1-beta-D-arabinofuranosyl cytosine, camptothecin, cisplatin, cyclophosphamide, daunorubicin, 5-flurouracil, 6-mercaptopurine, hydroxyurea, ionomycin, methotrexate and vincristine. With the exception of cyclophosphamide and hydroxyurea, a 36 h exposure to these drugs resulted in inhibition of cell growth and apart from cyclophosphamide, hydroxyurea. 6-mercaptopurine and cisplatin the induction of apoptosis. Studies using a decreased concentration of drug and exposure time (12 h) followed by examination of cells using flow cytometry indicated that most drugs were capable of affecting cell cycle progression without induction of apoptosis. However when cells were synchronised at G0/G1, S and G2/M phases and then exposed to these decreased concentrations of drug apart from 6MP an HU, apoptosis was observed and for the majority of drugs it took place in the same phase in which progression through the cell cycle was blocked by the drug. Cells synchronised in G0/G1 phase were more susceptible to methotrexate, whereas S-phase cells were more susceptible to camptothecin and 5-flurouracil and G2/M phase cells more susceptible to actinomycin D, 1-beta-D-arabinofuranosyl cytosine, daunorubicin and cisplatin. In contrast, vincristine blocked cells in G2/M phase but exerted its apoptotic effect in S-phase cells, ionomycin had no effect on the cell cycle, but G2/M cells appeared to be more susceptible to the effect of this drug. These data indicate that entry into apoptosis by this fibrosarcoma may occur at any point in the cell cycle. They also demonstrate a correlation between the action of some anticancer drugs on the cell cycle and the subsequent induction of apoptosis which may be useful in chemotherapeutic design.

Animals↗
PubMed1997

Parental alcoholism and other family disruptions: adult outcomes among sisters.

Adult outcomes were investigated in 14 pairs of African-American and white daughters of alcoholic parents. On the basis of four outcome factors, subjects were divided into three sister-pair categories: well-adjusted, impaired, and mixed. Interviews and standardized questionnaires showed that family-of-origin variables contributing to the impaired adult outcomes included parental psychiatric problems and childhood abuse or neglect.

Adult↗
PubMed1997

Urogenital ageing and its effect on sexual health in older British women.

OBJECTIVE: To provide information on the extent of problems of urogenital ageing in older British women. DESIGN: A MORI survey of a representative population sample of older British women. SETTING: Home interviews. PARTICIPANTS: Two thousand and forty-five women aged 55-85+. RESULTS: Urogenital symptoms had affected 48.8% of the women at some time, but no more than 11% were currently affected by individual symptoms; however, these were often of long duration. The majority (73%) were not sexually active, with lack of a partner being a factor for many. There was also a decreasing prevalence of sexual activity with increasing age. Those sexually active in the 65-74 year old age group (n = 148) tended to have a similar sexual frequency (at least once per month) compared with the younger women studied. Approximately 12% of those who reported dyspareunia and/or vaginal dryness claimed a severe problem; 33% did not seek professional advice and 36% resorted to an over the counter remedy. Use of hormone replacement therapy was generally of relatively short duration. There was a declining gradient of ever-use with age. CONCLUSIONS: The extent of significant urogenital symptoms is relatively low, but some women are seriously affected and use self-help as well as professional assistance. The extent of sexual activity in older women and factors affecting this have been defined, and the effect of urogenital symptoms on sexual activity demonstrated.

Aged↗
PubMed1997

Reduced expression of tissue transglutaminase in a human endothelial cell line leads to changes in cell spreading, cell adhesion and reduced polymerisation of fibronectin.

Tissue transglutaminase (tTgase, type II) is a Ca2+-dependent GTP binding protein which crosslinks proteins via (epsilon)((gamma)-glutamyl)lysine bridges. Although essentially a cytosolic enzyme there is increasing evidence to suggest the enzyme is externalised where it may play a role in extracellular matrix organisation. To investigate the function of this enzyme in a human umbilical endothelial cell line ECV304 tTgase expression was reduced in these cells by up to 90% by stable transfection with a 1.1. kb antisense construct in the plasmid vector pSG5. Two clones showing a reduction in expression of tTgase activity of 70 and 90% have been isolated and characterised. These clones show a number of phenotypic differences when compared to the parent cell line and the transfected controls which include reduced cell spreading and a decreased adhesion of cells on different substrata as measured by their susceptibility to removal by trypsin. Reduced cell spreading in the antisense transfected clones was accompanied by a decrease in the crosslinking of fibronectin into polymeric multimers which could be correlated to the amount of tTgase externalised by cells. A novel assay was developed to measure externalised tTgase activity which is cell mediated, inhibited by preincubation of cells with anti-tTgase antibody and relies on the incorporation of biotinylated cadaverine into fibronectin. The results of these experiments suggest that externalised tTgase may play a key role in a number of cell behavioural patterns which might be related to the enzymes ability to bind and crosslink fibronectin.

Antibodies, Monoclonal↗
PubMed1996

Risk factors for outbreaks of infectious intestinal disease linked to domestic catering.

The epidemiology of general outbreaks of infectious intestinal disease associated with domestic catering for large numbers is described and compared with foodborne outbreaks in other settings. From 1 January 1992 to 31 December 1994, the PHLS Communicable Disease Surveillance Centre identified 101 foodborne general outbreaks of infectious intestinal disease associated with domestic catering in England and Wales (16% of all foodborne outbreaks). Salmonella species were associated with 77 of the 101 outbreaks and S. enteriditis phage type 4 accounted for 57. Small round structured viruses were implicated in five outbreaks, Clostridium perfringens in four, Bacillus cereus in two, and Campylobacter sp and Escherichia coli in one each. No pathogen was identified in 11 outbreaks. Outbreaks occurred most commonly in summer. The commonest vehicles implicated were poultry/eggs in 44 outbreaks, desserts in 13, and meat/meat products in nine. Salad/vegetables, sauces, and fish/shellfish were each implicated in eight outbreaks. Raw shell eggs were implicated in a fifth of outbreaks. Inappropriate storage was the commonest fault, reported in association with 50 outbreaks (ambient temperature for long periods before serving in 29), inadequate heat treatment was reported in 35, cross contamination in 28, an infected food handler in 11, and other faults in 14. Outbreaks associated with catering on domestic premises were independently more likely than outbreaks in other settings to be associated with salmonellas, inappropriate storage of food, and consumption of poultry, eggs, or sauces. Public health services need to direct messages about the use, preparation, and storage of food to those who cater on domestic premises.

Disease Outbreaks↗
PubMed1996

The novel anthracycline annamycin is not affected by P-glycoprotein-related multidrug resistance: comparison with idarubicin and doxorubicin in HL-60 leukemia cell lines.

A major factor in limiting the efficacy of anthracyclines is overexpression of the MDR1-encoded p-glycoprotein (p-gp). A new analogue less affected by p-gp is annamycin (ANN), an anthracycline antibiotic with high affinity for lipid membranes and significantly more activity than doxorubicin (DOX). We investigated whether ANN was affected by p-gp-mediated multidrug resistance (MDR) by comparing the cellular accumulation and retention of ANN, idarubicin (IDR), and DOX in the p-gp-negative human leukemia cell lines (HL-60S) and its DOX-selected p-gp-positive subline (HL-60/DOX) with and without verapamil (VER). As expected, HL-60/DOX cells showed lower DOX uptake than HL-60S cells; coincubation with VER (10 mmol/L) increased uptake 2.6-fold restoring it to 100% of uptake in HL-60S cells. IDR uptake increased 1.5-fold in the presence of VER, but ANN was not affected. Coincubation with VER increased DOX retention in HL-60/DOX cells 2.8-fold and IDR retention 1.4-fold; unchanged ANN retention indicated that ANN may overcome p-gp. In the cytotoxicity assay to correlate intracellular anthracycline content with antitumor activity, we found ANN to be less potent than DOX and IDR In sensitive cells, ID 50 being the drug concentration that inhibits cell growth by 50% but its resistance index (RI; ID50 resistant cells divided by ID50 sensitive cells) was lower than that of IDR and DOX (2.6 v 40 and 117.5). Coincubation in the presence of VER resulted in 4.5-fold and 2-fold RI decreases of DOX and IDR, respectively, whereas ANN did not change, further confirming ANN's ability to circumvent p-gp-mediated MDR. Confocal microscopy studies of IDR, ANN, and DOX showed higher intracellular drug compartmentalization for DOX in HL-60/DOX cells incubated in the presence of VER. This study provided evidence that, unlike DOX and IDR, ANN is not affected by p-gp-mediated MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis.

OBJECTIVE: To compare the relative risks of serious gastrointestinal complications reported with individual non-steroidal anti-inflammatory drugs. DESIGN: Systematic review of controlled epidemiological studies that found a relation between use of the drugs and admission to hospital for haemorrhage or perforation. SETTING: Hospital and community based case-control and cohort studies. MAIN OUTCOME MEASURES: (a) Estimated relative risks of gastrointestinal complications with use of individual drugs, exposure to ibuprofen being used as reference; (b) a ranking that best summarised the sequence of relative risks observed in the studies. RESULTS: 12 studies met the inclusion criteria. 11 provided comparative data on ibuprofen and other drugs. Ibuprofen ranked lowest or equal lowest for risk in 10 of the 11 studies. Pooled relative risks calculated with exposure to ibuprofen used as reference were all significantly greater than 1.0 (interval of point estimates 1.6 to 9.2). Overall, ibuprofen was associated with the lowest relative risk, followed by diclofenac. Azapropazone, tolmetin, ketoprofen, and piroxicam ranked highest for risk and indomethacin, naproxen, sulindac, and aspirin occupied intermediate positions. Higher doses of ibuprofen were associated with relative risks similar to those with naproxen and indomethacin. CONCLUSIONS: The low risk of serious gastrointestinal complications with ibuprofen seems to be attributable mainly to the low doses of the drug used in clinical practice. In higher doses ibuprofen is associated with a similar risk to other non-steroidal anti-inflammatory drugs. Use of low risk drugs in low dosage as first line treatment would substantially reduce the morbidity and mortality due to serious gastrointestinal toxicity from these drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Measurement of tissue transglutaminase activity in a permeabilized cell system: its regulation by Ca2+ and nucleotides.

Electropermeabilized human endothelial cells (ECV-304) were used to study the regulation of tissue transglutaminase (tTGase) activity in the intracellular environment. An ELSA (enzyme-linked sorbent assay) plate assay was developed for intracellular tTGase activity, using the incorporation of a biotinylated primary amine, 5-{[(N-biotinoylamino)hexanoyl]amino}pentylamine(biotin-x-cadaveri ne; BTC), into endogenous protein substrates of tTGase. This incorporation process was inhibited by competitive inhibitors of tTGase, cystamine and monodansylcadaverine, in a dose-dependent manner. Over a 30 min period tTGase and its protein substrates did not leak out of the cell, and no incorporation of BTC occurred in unpermeabilized cells, indicating the reaction to be intracellular. In the presence of 10 nM or 10 muM CA2+, when nucleotides ATP and GTP were added at concentrations mimicking cytosolic levels, tTGase activity was decreased virtually to zero. Only at 100 muM Ca2+, when nucleotides were low or absent was tTGase activity observed. Under these conditions a variety of proteins was labelled by the enzyme, with the major labelling found in a protein of molecular mass around 51 kDa when analysed by SDS/PAGE/Western blotting.

Adenosine Diphosphate↗
PubMed1996

Adult immunizations.

New vaccines have been licensed for hepatitis A, varicella, and typhoid. This paper reviews these vaccines and their recommended uses in adults. Special attention is given to a new national policy establishing age 50 years as a time for review of preventive health measures with emphasis on evaluating risk factors that indicate a need for pneumococcal vaccine and the initiation of annual influenza immunization.

Adult↗
PubMed1996

Fatalities in the construction industry in the United States, 1992 and 1993.

To improve the estimates of occupational fatality rates for persons employed in the construction industry, several sources of data on the number of fatalities (the numerator) and the number of persons engaged in construction work (the denominator) were examined. Based on this examination, the Census of Fatal Occupational Injuries (CFOI), complied by the Bureau of Labor Statistics (BLS), was used to obtain numerators and the Current Population Survey, conducted by the Bureau of the census for the BLS, was used to obtain denominators. Adjustments were made in the numerator to include only occupations that were included in the denominator. Occupations were divided into two groups-those in the construction trades and those in other occupations within construction (e.g., clerical, sales). The analysis found fatality rates of 14.2 and 13.3 per 100,000 person-years, respectively, for 1992 and 1993, with wide variation in rates among the different trades. There were also major differences among the trades in the types of fatal injuries. Self-employed workers had much lower death rates overall than wage workers, but this is largely due to much lower proportions of high hazard trades among the self-employed. There have been wide variations in the occupational fatality rates reported for construction workers each year due to the differing methods of estimating the number of fatalities by the different data sources. This study provides a baseline of fatality rates using the best available current data. It compares the results from these data sources with those from other sources that have been used and discusses some of the problems inherent in the data from other sources. This study provides a significantly improved protocol for the calculation of fatality rates against which later rates can be compared consistently. Nevertheless, many deficiencies in the data sources used are identified. There remains ample room for continued improvement.

Accidents, Occupational↗