PubMed Health⌕ Search

Biomedical subjects

G Coffey

Publications and source records attributed to G Coffey.

13 recordsLinked to original sources
PubMed2000

An alternate form of Ku80 is required for DNA end-binding activity in mammalian mitochondria.

Mammalian mitochondrial DNA end-binding activity is nearly indistinguishable from that of nuclear Ku. This observation led to the hypothesis that mitochondrial DNA end-binding activity is in part dependent upon Ku80 gene expression. To test this hypothesis, we assayed for Ku activity in mitochondrial extracts prepared from the xrs-5 hamster cell line that lacks Ku80 mRNA expression. Mitochondrial protein extracts prepared from this cell line lacked the DNA end-binding activity found in similar extracts prepared from wild-type cells. Azacytidine-reverted xrs-5 cells that acquired nuclear DNA end-binding activity also acquired mitochondrial DNA end-binding activity. Western blot analysis of human mitochondrial protein extracts using a monoclonal antibody specific for an N-terminal epitope of Ku80 identified a protein with an apparent molecular weight of 68 kDa. This mitochondrial protein was not detected by a monoclonal antibody specific for an epitope at the C-terminal end of Ku80. Consistently, while both the N- and C-terminal Ku80 monoclonal antibodies supershifted the nuclear DNA end-binding complex on an electrophoretic mobility shift assay, only the N-terminal monoclonal antibody supershifted the mitochondrial DNA end-binding complex. To confirm that the 68 kDa Ku protein was not a consequence of nuclear protein contamination of mitochondrial preparations, highly purified intact nuclei and mitochondria were treated with proteinase K which traverses the pores of intact nuclei but gains limited access into intact mitochondria. Ku80 in purified intact nuclei was sensitive to treatment with this protease, while the 68 kDa Ku protein characteristic of purified intact mitochondria was resistant. Further, immunocytochemical analysis revealed the co-localization of the N-terminal specific Ku80 monoclonal antibody with a mitochondrial-targeted green fluorescence protein. Mitochondrial localization of the C-terminal Ku80 monoclonal antibody was not observed. These data are consistent with the hypothesis that a C-terminally truncated form of Ku80 is localized in mammalian mitochondria where it functions in a DNA end-binding activity.

Animals↗
PubMed1999

Mammalian mitochondrial extracts possess DNA end-binding activity.

Mammalian mitochondrial protein extracts possess DNA end-binding (DEB) activity. Protein binding to a 394 bp double-stranded DNA molecule was measured using an electrophoretic mobility shift assay. Mitochondrial DEB activity was highly specific for linear DNA. Inclusion of a vast excess of non-radioactive circular DNA did not disrupt binding to radioactive f394. In contrast, binding was abolished by the inclusion of linear competitor DNA. In mammals, nuclear DEB activity is due to Ku, a hetero-dimer composed of the Ku70 and Ku86 proteins. To determine whether mitochondrial DEB activity was also due to Ku, protein extracts were prepared from the Chinese hamster XR-V15B cell line, which lacks this protein. As anticipated, nuclear extracts prepared from these cells lacked DEB activity. In contrast, mitochondrial extracts prepared from these cells had wild-type levels of DEB activity, demonstrating that this latter activity is not a consequence of nuclear contamination. Although the nuclear and mitochondrial DEB activities are independent of each other, they are nevertheless closely related, since mitochondrial DEB activity was 'supershifted' by both anti-Ku70 and anti-Ku86 antisera. The nuclear DEB protein Ku plays an essential role in nuclear DNA double-strand break repair. The DEB activity described herein may therefore play a similar role in mitochondrial DNA repair.

Animals↗
PubMed1999

Polymicrobial brain stem abscess due to Streptococcus anginosus and Actinomyces species.

This report describes a rare case of a pyogenic brain stem abscess. The lesion was readily identified by computed tomographic (CT) scan and magnetic resonance imaging (MRI). Streptococcus anginosus was grown from the pus and Actinomyces colonies were found on histopathology. The lesion was successfully treated with stereotactic surgery and antibiotic therapy. A review of the relevant literature including the role of stereotaxy in the treatment of the brain stem abscess is discussed. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMed1998

Amphotericin B colloidal dispersion for treatment of candidemia in immunocompromised patients.

The efficacy and safety of amphotericin B colloidal dispersion (ABCD; Amphotec, Sequus Pharmaceuticals, Menlo Park, CA), a lipid complex of amphotericin B, were evaluated in immunocompromised patients with candidemia. These patients were recruited from five open-label clinical trials of ABCD therapy for fungal infections subsequent to bone marrow transplantation, hematologic malignancies, solid tumors, solid-organ transplantation, or other severe underlying disorders. ABCD was given intravenously in a median daily dose of 3.9 mg/kg for < or =72 days. Response rates were as follows: 53% overall (n = 88), 66% for patients with candidemia alone (n = 67), and 14% for patients with disseminated candidemia (n = 21). Nephrotoxicity occurred in 16% of patients, with either doubling of the baseline serum creatinine level or an increase of > or =1 mg/dL or a > or =50% decrease in calculated creatinine clearance. On average, there were no significant changes in the levels of serum creatinine or bilirubin from baseline to the end of treatment. In conclusion, ABCD was safe and effective for treating immunocompromised patients with candidemia.

Adolescent↗
PubMed1998

Lowering the language barrier in an acute psychiatric setting.

OBJECTIVES: The aim of this paper is to investigate the effectiveness of a training and policy strategy to improve communication opportunities in an acute inpatient unit for patients of non-English-speaking background (NESB) with low English proficiency. METHOD: A pre- and post-intervention design involved: (i) a survey of the multilingual skills of 80 clinical staff; (ii) recording of patients' ethnic background and proficiency; (iii) pre- and post-intervention data collection of the main outcome measure (communications with patients in a language other than English [LOTE]); and (iv) staff training, and active encouragement, in interpreter use. English proficiency was assessed using the population census proficiency question. RESULTS: Of 257 admissions, 33% were of NESB and 19% preferred to speak a LOTE. The staff survey yielded a 49% return rate and showed that, of 11 LOTEs spoken by patients, seven were also spoken by 17 of the staff. Twenty-nine percent of staff were not clinically proficient in these languages. Compared to the NESB population, a higher proportion of NESB patients rated low on proficiency. Following the intervention, interpreter bookings and booking duration increased significantly. CONCLUSIONS: A standard training package and a policy promoting interpreter use improved communication opportunities in an acute setting where language needs are typically poorly met. Failure to ensure effective communicate raises risks of misdiagnosis and inappropriate treatment. By measuring patients' proficiency directly, the present study identified a higher level of need for interpreter services than estimated by past reports.

Acute Disease↗
PubMed1994

Reported diabetes mellitus management among South Australian general practitioners.

Diabetes mellitus is a chronic disease commonly managed in general practice. This article reviews the findings of a questionnaire survey of 173 randomly chosen South Australian general practitioners and their reported management in the areas of detection, diagnosis, assessment, monitoring and GP knowledge. Substantial differences between respondents were found in all areas, suggesting the need for improved educational methods aimed at all general practitioners.

Adult↗
PubMed1994

Knowledge of and reported asthma management among South Australian general practitioners.

AIM: This study, carried out in 1989, set out to assess general practitioners' knowledge of asthma management and their reported management practices. METHOD: Of 153 randomly selected South Australian general practitioners 127 (83%) completed a questionnaire designed to explore issues relating to the management of asthma. RESULTS: The survey revealed substantial differences between general practitioners in their knowledge and management practices including the assessment of the severity of asthma, the need for objective monitoring, that is by the use of spirometry and peak flow meters, and the use of medication. Overall, the sampled general practitioners believed that patient-related factors were the main barriers to effective treatment of asthma. CONCLUSION: The findings of this study suggest that ideal asthma management was not being attained. More research is required to ascertain why such variability among practitioners exists and how best to remedy these differences.

Adult↗
PubMed1993

A pattern of decline in general practice obstetric care in Adelaide.

Some educational, training and politico-economic reasons for the decline in GP obstetrics in Adelaide, South Australia, are described. It is recommended that similar studies be done in other centres in Australia to evaluate the general nature of the findings.

Clinical Competence↗
PubMed1991

Signs, symptoms, and the new descriptors.

Data from 143 consultations in general practice were assessed by factors relevant to the four-category descriptive system developed by the Royal Australian College of General Practitioners. It seems that there is no relationship between consultation length, apparent symptom seriousness or the occurrence of a physical examination. Suggestions are offered for improving the clarity of consultation descriptor categories.

Diagnosis↗