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Biomedical subjects

J Davies

Publications and source records attributed to J Davies.

At least 163 records · Page 9Linked to original sources

Tolerate, engage or withdraw: a study of the structure of families coping with alcohol and drug problems in south west England and Mexico City.

AIMS: To explore the structure underlying individual differences in the ways family members cope with drinking or drug problems. DESIGN: Cross-sectional interview and questionnaire study of a series of family members in two contrasting socio-cultural groups. SETTING: Mexico City and South West England. PARTICIPANTS: Two hundred and seven family members from separate families, three-quarters women, one-quarter men, mostly partners or parents. DATA: Long semi-structured interviews; the Coping Questionnaire (CQ). FINDINGS: Factor and subscale analyses of the CQ data and textual analysis of the interview reports were used to test the hypothesis that the underlying structure to coping could be described in terms of eight or nine coherent and distinct ways of coping. Neither form of analysis gave strong support to this hypothesis. CONCLUSIONS: It is concluded that the structure of coping can best be described in terms of three broad coping positions: tolerating, engaging and withdrawing. These conclusions challenge some previous assumptions about functional and dysfunctional ways of coping with excessive appetitive behaviour in the family.

Adaptation, Psychological↗

Allogeneic bone marrow transplantation for systemic AL amyloidosis.

Low-intensity chemotherapy is ineffective in most patients with AL amyloidosis, probably because clinical benefit requires regression of the amyloid deposits, and this occurs only very gradually after the underlying plasma cell dyscrasia has been suppressed. We report the first successful allogeneic bone marrow transplant (allo-BMT) for AL amyloidosis, which after 3 years was associated with complete clinical recovery. This supports the idea that there may be a brief window of opportunity in patients with AL amyloidosis during which dose-intensive chemotherapy is feasible and most likely to produce clinical benefit.

Amyloidosis↗

Probing the active site of mitogillin, a fungal ribotoxin.

Fungal ribotoxins, such as mitogillin and the related Aspergillus toxins restrictocin and alpha-sarcin, are highly specific ribonucleases, which inactivate the ribosome enzymatically by cleaving the eukaryotic 28S RNA of the large ribosomal subunit at a single phosphodiester bond. The site of cleavage occurs between G4325 and A4326, which are present in a 14-base sequence (the alpha-sarcin loop) conserved among the large subunit rRNAs of all living species. The amino acid residues involved in the cytotoxic activities of mitogillin were investigated by introducing point mutations using hydroxylamine into a recombinant Met-mature mitogillin (mitogillin with a Met codon at the N-terminus and no leader sequence) gene constructed from an Aspergillus fumigatus cDNA clone. These constructs were cloned into a yeast expression vector under the control of the GAL1 promoter and transformed into Saccharomyces cerevisiae. Upon induction of mitogillin expression, surviving transformants revealed that substitutions of certain amino acid residues on mitogillin abolished its cytotoxicity. Non-toxic mutant genes were cloned into an Escherichia coli expression vector, the proteins overexpressed and purified to homogeneity and their activities examined by in vitro ribonucleolytic assays. These studies identified the His-49Tyr, Glu-95Lys, Arg-120Lys and His-136Tyr mutations to have a profound impact on the ribonucleolytic activities of mitogillin. We conclude that these residues are key components of the active site contributing to the catalytic activities of mitogillin.

Allergens↗

HIV-associated brain pathology: a comparative international study.

Little is known about the frequency and variation of HIV-associated brain pathology in different geographical centres. To assess whether there is an association between the frequency of disease and demographic factors we examined the neuropathological findings in four European and two American cities. The cities included London, Edinburgh, Paris, Budapest, Baltimore and Newark. Information was collected on a total of 1144 cases. HIV encephalitis was the most common observation in all the centres. although its frequency varied between them (P < 0.01). Furthermore, there were significant differences (P < 0.001) between the various categories of exposure and the frequency of HIV encephalitis in Edinburgh and other centres. The occurrence of toxoplasmosis, progressive multifocal leukoencephalolpathy (PML) and cryptococcal infection also differed between the various centres (P < 0.01). None of the findings was attributable to age, sex, or ethnic origin, but the introduction of anti-retroviral treatment, such as Zidovudine, may have been important. Overall, this study highlights geographical variability and the potential importance for group of exposure and anti-retroviral medication as factors affecting the development of various HIV-associated brain lesions.

AIDS Dementia Complex↗

Hepatitis G virus infection in lymphoma and in blood donors.

AIMS: To determine whether the recently described flavivirus, hepatitis G virus (HGV), might contribute to the pathogenesis of lymphoma by testing for the presence of HGV RNA in sera from patients attending lymphoma clinics; to compare the incidence of HGV RNA in lymphoma patients with that in normal blood donors; and to look for potential risk factors for HGV infection and for evidence of hepatic disease in the HGV positive patients. METHODS: Sera were examined from 76 patients with lymphoma and 100 blood donors for the presence of HGV RNA using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: HGV RNA was detected in 10% of patients' sera, but only in 1% of blood donor samples. HGV infection was found in patients with various different types of lymphoma, including Hodgkin's disease and non-Hodgkin's lymphoma. The majority (75%) of patients who were HGV PCR positive had undergone transfusion, but only 30% of those who were HGV PCR negative had received blood products. In addition, the number of donor exposures per HGV positive patient was approximately twice that of the HGV negative group. CONCLUSIONS: The data suggest (1) that HGV is present in the normal blood donor population; (2) that patients with lymphoma are at risk of acquiring HGV because of their exposure to blood products; and (3) that persistent HGV infection does not appear to cause serious liver disease in these patients.

Adult↗

Distal 10q trisomy syndrome with unusual cardiac and pulmonary abnormalities.

Since its description in 1965, distal 10q trisomy has become recognised as a well defined, although rare syndrome, almost always the result of an unbalanced translocation. Typical features consist of psychomotor delay, a distinctive dysmorphic appearance, growth retardation, and, in some cases, cardiac, renal, and ocular abnormalities.

Abnormalities, Multiple↗

Environmental influence on immune inhibition of release of herpes simplex virus from cells.

Immune inhibition of virus release (IVR) of herpes simplex virus type 1 (HSV-1) from baby hamster kidney cells (BHK-21) was mediated by antisera against BHK cells, HSV-1, human fibronectin and mouse heparan sulphate proteoglycan and was irreversible for at least 24 h following removal of antiserum. Enhancement of IVR by calf serum depletion of growth media was obtained in varying measure using each of these antisera and also by treatment of virus-infected cells by the lectin concanavalin A. Enhancement was reversible by replenishment of growth media with bovine serum components larger than 12 kD but this only occurred when replenishment was instituted prior to virus infection. There was also reversibility to varying degree following replenishment by ovine, equine and human serum which indicates that this phenomenon is not species specific. In addition to the presence of relevant antigens on the cell surface, IVR may also require an alteration in the cell membrane; this is evidenced by the absence of anticellular serum-mediated IVR when treatment was introduced less than 6 h after virus infection, suggesting that a certain level of alteration or possibly cell damage - in this case virus induced - is necessary. Enhancement of IVR by calf serum depletion would seem to operate through a specific alteration in the virus-infected cell membrane as serum-depleted cells did not show histological alteration and were able to replicate HSV-1 to usual titres; it is possible that this enhancement may represent an as yet unidentified host defence mechanism whereby extracellular release of virus will be reduced in ischaemic or necrotic tissue in the course of infectious inflammatory processes.

Animals↗

Antiviral efficacy of disinfectant solution MRI-1.

Disinfectant MRI-1 was prepared by dissolution of non-ionic and ionic detergent in ethanol. The disinfectant inactivated extracellular and intracellular enveloped and non-enveloped viruses including herpes viruses, influenza A and human immunodeficiency disease virus in suspension or on surfaces by pre-exposure or post-exposure to the disinfectant; in addition, cells were disabled as potential hosts for viral infection using concentrations of MRI-1 which were 50-fold less than the operative concentration for disinfection. There was no evidence of in vitro mutagenicity using Salmonella typhimurium or sensitization or other adverse effect in a guinea pig model or in human subjects.

Animals↗

The renaissance of microbiology.

Microbiology is finally occupying its true position as the pre-eminent field in life sciences. This is due to advances in molecular techniques that confirm the evolutionary significance of the biology of microbes. It is anticipated that the use of comparative genomics will provide information that will advance the understanding of mechanisms of pathogenesis and the importance of secondary metabolism in social microbiology. More emphasis on studies of microbial diversity will increase its value in both fundamental microbiology and its industrial applications.

Biological Evolution↗

Antibiotic resistance in mycobacteria.

Multiple drug resistance in mycobacteria compromises the use of antibiotics. Although the genetic and biochemical bases of antibiotic resistance in mycobacteria are largely understood, a number of questions remain to be addressed. This chapter discusses the potential roles of hypermutability and compensatory mutations in establishing stable resistant phenotypes in the pathogenic mycobacteria.

Amino Acid Sequence↗

Production of bleomycin N-acetyltransferase in Escherichia coli and Streptomyces verticillus.

Bleomycin-producing Streptomyces verticillus ATCC 15003 has two bleomycin resistance genes, designated blmA and blmB. Bleomycin N-acetyltransferase, encoded by blmB, was overproduced in Escherichia coli as a protein fused to the maltose-binding protein. The protein (fBAT), purified to homogeneity after digestion of the fusion product with blood coagulation factor Xa protease, had an additional 6 N-terminal amino acid residues, but retained its bleomycin-acetylating activity, as did the entire fusion protein. The K(m) and Vmax values of purified fBAT for the substrate bleomycin were 13.0 microM and 3.4 nmol [corrected] min-1 ml-1, respectively. The optimal pH for the acetylating activity was 6.0 in 10 mM phosphate buffer. The molecular mass and pI value of fBAT were estimated by polyacrylamide gel electrophoresis to be about 34500 and 6.13, respectively. An anti-fBAT monoclonal antibody was generated and used to show that bleomycin N-acetyltransferase is expressed simultaneously with bleomycin production in S. verticillus.

Acetyltransferases↗

HIV-associated brain pathology in the United Kingdom: an epidemiological study.

OBJECTIVES: To examine the epidemiology of HIV-associated neuropathology in the United Kingdom and to investigate whether the prevalence of different forms of HIV-associated brain pathology varies with exposure category. DESIGN: The study was a cross-sectional survey; data was analysed from the Medical Research Council National AIDS Neuropathology database. SETTING: Information was gathered from throughout England, Scotland and Wales. SUBJECTS: Individuals who died from AIDS in the United Kingdom and had a postmortem examination. The database comprised 7% of all AIDS deaths in the United Kingdom between 1982 and 1993. MAIN OUTCOME: Neuropathological diagnoses based on internationally accepted neuropathological terminology of AIDS-related brain lesions. RESULTS: HIV encephalitis was the most prevalent pathological diagnosis, occurring in 25.3% [95% confidence interval (CI), 21.0-29.6] of the study sample. Statistically significant independent associations for the occurrence of HIV encephalitis were found for injecting drug use (odds ratio, 6.86; 95% CI, 2.91-16.17), and age less than 30 years at death (odds ratio, 3.58; 95% CI, 1.99-6.44). Vascular lesions were significantly higher among blood product recipients, 95% of whom were haemophiliacs. CONCLUSIONS: This was the first epidemiological investigation of HIV-associated brain pathology in the United Kingdom. HIV encephalitis appeared to occur more frequently in injecting drug users and those who died younger. Whereas the findings must be interpreted cautiously, one hypothesis was that differences in the route of transmission may have affected the manifestation of HIV-associated brain damage.

AIDS Dementia Complex↗

Detection of antigen-antibody binding events with the atomic force microscope.

An atomic force microscope (AFM) has been used to directly monitor specific interactions between antibodies and antigens employed in an immunoassay system. Results were achieved using AFM probes functionalized with ferritin, and monitoring the adhesive forces between the probe and anti-ferritin antibody-coated substrates. Analysis of the force distribution data suggests a quantization of the forces, with a period of 49 +/- 10 pN. This periodic force may be attributed to single unbinding events between individual antigen and antibody molecules. These results demonstrate that the AFM could be employed as an analytical tool to study the interactions between the molecules involved in biosensor systems. The potential of the technique to provide information relating to the manner in which the antibody molecule binds to its specific antigen is also discussed.

Animals↗

Self-esteem, eating problems, and psychological well-being in a cohort of schoolgirls aged 15-16: a questionnaire and interview study.

OBJECTIVE: This study aimed to investigate the extent of eating problems and their association with self-esteem in girls aged 15-16. METHOD: Six hundred and nine schoolgirls aged 15-16 completed a questionnaire examining eating behavior, self-esteem, and general psychological well-being. A subsample of 31 girls was subsequently interviewed in terms of eating behavior and self-esteem. RESULTS: The questionnaire findings revealed that 56% of girls felt too fat and had used some form of weight control strategy. In addition, 32% scored above the Hospital Anxiety and Depression Scale (HADS) threshold for anxiety and 43% reached the Rosenberg Self-Esteem Scale criterion for low self-esteem. Interviews confirmed that those showing abnormal eating behavior in the questionnaires did indeed show greater eating pathology as well as lower self-esteem. Interviews also revealed that those with high levels of eating concern showed greater levels of global self-dissatisfaction and higher dissatisfaction with their physical appearance and family relationships. DISCUSSION: The results suggest that preventative interventions targeted at girls with low self-esteem may be appropriate.

Achievement↗

Retrospective review of the effects of rhDNase in children with cystic fibrosis.

Trials of rhDNase in mixed groups of adults and children with cystic fibrosis (CF) have demonstrated improvements in lung function and well-being. This has led to many pediatric CF patients receiving regular rhDNase therapy although their response to treatment may not be the same as that seen in adults. We have retrospectively reviewed the effects of rhDNase during the first year of therapy in 65 children receiving the drug at two tertiary referral centers. Outcome measures included changes in lung function, oxygen saturation, use of intravenous antibiotics, and subjective improvement. Median baseline lung function (% of predicted) was 45% for forced expiratory volume in 1 second (FEV1) and 58% for forced vital capacity (FVC). At 3-4 months following initiation of therapy the group demonstrated median (95% CI) increases of 14.2% (95% CI 7.3; 21.1%) in FEV1 and 7% (0; 14%) in FVC. Within this wide scatter of responses, one-quarter of children deteriorated, but almost 50% showed significant improvements of > 10%. A similar pattern was seen at 9 months, with median increases for the group of 11.1% (0; 18.8%) in FEV1 and 5.6% (0; 17%) in FVC, again with approximately one-third of the group deteriorating and one-half improving significantly. Intravenous antibiotic use decreased significantly. Almost all the children (89%), including those with a fall in lung function, described subjective improvement. There were no predictive markers at baseline of a good response to the drug. However, there was a good correlation between lung function response at 3 months and that at 6, 9, and 12 months. Thus, children respond to rhDNase at least as well as adults, and a therapeutic trial is justified in those over 5 years with significantly impaired lung function. Response is highly variable, making careful individual assessment mandatory. Baseline characteristics are not useful in predicting those children who will respond well to treatment, but long-term response to the drug can be predicted on the basis of spirometric improvement at 3 months. Therefore, this would be a useful time period for a therapeutic trial.

Adolescent↗

Does ice immersion influence ankle joint position sense?

The purpose of this study was to determine whether a fifteen minute ice immersion treatment influenced the normal ankle joint position sense at 40% and 80% range of inversion and to establish the length of treatment effect through monitoring the rewarming process. Forty nine healthy volunteers between the ages of 17 and 28 were tested. Subjects were screened to exclude those with a history of ankle injuries. The subject's skin temperature over antero-lateral aspect of the ankle was measured using a thermocouple device during the fifteen minutes ice intervention and thirty minutes post-intervention. Testing of ankle joint position sense using the pedal goniometer was performed before and after a clinical application of ice immersion. The testing required the subject to actively reposition their ankle at 40% and 80% of their total range of inversion. The majority of subjects experienced numbness of the foot and ankle by the fifth or sixth minute during ice immersion. One minute after immersion skin temperatures averaged 15 degrees C + 1.7 degrees C. Skin temperature was seen to rise relatively rapidly for the first ten minutes and then slowed considerably. Subjects had not returned to the pre-test skin temperatures by thirty minutes. A significant difference in ankle joint position sense (p < 0.0499) following fifteen minutes of ice immersion was found. However, the magnitude of this difference (0.5 degree) would not be deemed significant in clinical practice. The research found no significant difference in joint position sense between 40% and 80% of the range of inversion both before and after cryotherapy. These findings suggest that the clinical application of cryotherapy is not deleterious to joint position sense and assuming normal joint integrity patients may resume exercise without increased risk of injury.

Adult↗