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Biomedical subjects

R F Jones

Publications and source records attributed to R F Jones.

At least 55 records · Page 3Linked to original sources

Biochemical and genetic analysis of two acetyltransferases from hamster tissues that can metabolize aromatic amine derivatives.

Cytosolic activities in liver, stomach, small intestine, colon, lung, kidney, brain and spleen of hamster have been shown to be capable of N-acetylation, O-acetylation and N,O-acetyltransfer utilizing aromatic amine derivatives as substrates. These activities, which have been implicated in the metabolic activation and carcinogenicity of these compounds, were highest in the liver and small intestine. N-Acetylation could be demonstrated with either acetyl CoA or N-hydroxy-N-acetylaminoarenes serving as acetyl donors. Each of these tissues gave two immunoreactive bands (approximately 29 and 31 kDa) on Western blots using anti-rat AT monoclonal antibodies for detection. Single copies of two distinct acetyltransferase genes, designated AT1 and AT2, were detected in hamster DNA by Southern blot analysis using gene-specific hybridization probes for the 3' end of the AT coding regions. A third gene with > 80% sequence similarity to codons 118-158 of AT2 was also detected. Sequence analysis of the two AT genes showed that both had intronless, 0.87 kb coding regions. One was identical with the AT1 reported by Abu-Zeid et al. (Abu-Zeid,M., Nagata, K., Miyata,M., Ozawa,S., Fukuhara,M. and Yamazoe,Y., 1991, An arylamine acetyltransferase (AT-1) from Syrian golden hamster liver: cloning, complete nucleotide sequence, and expression in mammalian cells. Mol. Carcinogen., 4, 81-88). The second, AT2 (GenBank accession number L24912), coded for a 290 amino acid sequence that was 79% homologous with hamster AT1 and had a calculated molecular weight of 33.8 kDa, a theoretical pI of 5.96 and the three cysteines that have been conserved in all known vertebrate ATs at positions 44, 68 and 223. Northern blot hybridization using gene-specific AT probes detected mRNAs for both AT1 and AT2 in each of the eight tissues analyzed. Two AT1 transcripts, approximately 1.7 and 2.3 kb, were found in approximately equal ratios in all eight tissues. Three transcripts for AT2, approximately 1.9, 2.1 and 2.4 kb, were present in approximately equal ratios in the brain, small intestine, lung and colon. The liver, stomach, kidney and spleen had primarily the smaller two AT2 mRNAs. The overall abundance of AT mRNAs was highest in liver, small intestine and colon. The coding sequences of all AT mRNAs analyzed were identical to their corresponding genes, although the lengths of both the 5' and 3' untranslated transcript regions varied.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetyltransferases↗

Faculty and administration views of problems in faculty evaluation.

PURPOSE: To identify problems in how medical school faculty are evaluated, from the perspectives of faculty and administrators, and to understand how perceptions of the problems differ among those with varying roles within the medical school. METHOD: In March 1992 seven copies of an open-ended questionnaire were sent to each dean at the 126 accredited U.S. medical schools and 16 affiliated Canadian schools. The deans were instructed to complete one form themselves and to distribute one copy each to (1) a faculty affairs dean, (2) a basic science chair, (3) a clinical chair, (4) a member of chair of the school's promotion and tenure committee, (5) a senior faculty member, and (6) a junior faculty member. The authors conducted a content analysis of narrative comments in response to a question that began "Please identify and briefly describe the most salient problems you observe at your institution in how faculty are evaluated." RESULTS: Of a possible 994 responses, 455 (46%) were received. The respondents were from 102 of the 126 U.S. medical schools (81%) and eight of the 16 Canadian schools (50%). Response rates for the respondent subgroups ranged from 27% for the deans to 57% for the clinical chairs. Overall, the most frequently mentioned problems concerned the evaluation of teaching. General complaints about the inadequacy of current methods to evaluate teaching performance were most common--more than one in four respondents raised this issue--but the respondents also had specific complaints about student evaluations of teaching and the insufficient recognition given to teaching in the academic reward system. The frequencies with which other concerns were expressed tended to be related to the respondents' roles. These problems included concerns about the methods and measures used to assess research and scholarship and the quality of clinical care, the nonuniformity of evaluation processes and criteria for promotion among departments, the absence of regular evaluations, and the failure to link the results of evaluation to salary. CONCLUSION: The study population was not random; indeed, it was probably biased toward those who felt strongly (and perhaps negatively) about the current evaluation system. Still, the intensity with which views were expressed was striking. Improving the evaluation of faculty teaching undoubtedly remains one of medical education's greatest challenges.

Canada↗

Tenure policies in U.S. and Canadian Medical Schools.

This report presents data on tenure policies in U.S. and Canadian medical schools. The data are drawn from the findings of a larger survey of faculty appointment and tenure policies, which was mailed to each medical school dean in December 1993. The deans were asked to complete the questionnaire themselves or direct it to a staff member knowledgeable about faculty personnel policies. Non-responding institutions were sent a follow-up letter two months later. The response rate for the written survey was 96%: 137 of a possible 142 schools responded, with the remaining five schools participating in an abbreviated telephone survey. Of the 142 U.S. and Canadian medical schools, 136 (96%) have tenure systems, although nine of these schools limit the award of tenure to basic science faculty. Over three-fourths of the schools that have tenure systems define tenure to include some kind of financial guarantee. Rarely does this financial guarantee cover total salary/compensation; typically it is restricted to a "base" or university component of salary. Twenty percent of the schools have fixed pre-tenure probationary periods for clinical faculty that are longer than seven years; another 11% report having either no fixed pre-tenure probationary period or one that is unlimited. In the last five years, 10% of medical schools have terminated a tenured faculty member "for cause." Data are also examined concerning policies governing the extension of the pre-tenure probationary period, the rank at which tenure is usually granted, consequences of a negative tenure decision, caps on tenure positions, vacated tenure positions, and tenure arrangements for VA faculty and PhD faculty in clinical departments.(ABSTRACT TRUNCATED AT 250 WORDS)

Canada↗

Modification of plasmid and bacteriophage DNA by aromatic amines: effects on survival, template activity, and mutagenicity.

The carcinogenic and mutagenic effects of the aromatic amines are believed to depend on their covalent modification of DNA, primarily through the formation of adducts at C8 of guanine. The actual biologic and biochemical responses to these adducts can be envisioned as the consequence of the abilities of the cell to repair the lesions, with or without fidelity, and the introduction of errors through bypass of the adducts by polymerases. A key question is whether changes in DNA sequence arise through the participation of common repair processes that cause mutations independent of adduct structure. Alternatively, do mutations arise through miscoding during polymerase bypass at the site of the adducts and are, therefore, more likely to produce sequence changes that are more characteristic of adduct structure? This question has been approached using single, site-specific, or randomly introduced aromatic amine DNA adducts in bacterial cells, and in vitro studies with DNA polymerases that employ site-specifically modified templates. The results of both approaches demonstrate that these adducts are distinguished readily by virtue of their structures, thus supporting the conclusion that mutagenic effects of the aromatic amines arise from their structures rather than from their triggering a common inaccurate repair response.

Amines↗

A nude rat model for in vivo studies of human transitional cell carcinogenesis.

A xenograft system was developed for studying experimental carcinogenesis of human transitional cells in vivo. Segments of human ureters were tied to an injection port, ligated at the opposite end, implanted into gamma-irradiated nude rats and weekly irrigated through the injection port with fresh PBS solution. Such implants maintained the normal histologic appearance of human urothelium for at least 20 weeks in vivo in the nude rats. In situ hybridization with a human repetitive sequence DNA probe showed that the urothelium and the submucosal connective tissue and smooth muscle were of human origin. The urothelial lining was positive with an immunohistochemical reaction for acidic cytokeratins. This model allows for the long-term direct exposure of human urothelium to bladder carcinogens for the purpose of induction of human transitional cell tumors.

Animals↗

D-dimer in the early diagnosis of thromboembolic disease in acute spinal injuries.

The role of monitoring plasma levels of D-dimer (XDP) as a diagnostic aid for thromboembolic disease was investigated in 267 patients admitted for acute care to the Prince Henry Hospital Spinal Unit. Elevated plasma XDP levels were found in 103 patients (39%) and a diagnosis of thromboembolic disease was made in 33. Thromboembolic disease was not found in patients whose XDP levels remained normal.

Acute Disease↗

Colonic volvulus in the spinal cord injured patient.

At the Prince Henry Hospital between 1970 and 1987, 8 cases of colonic volvulus were diagnosed in spinal cord injured (SCI) patients. This represents an incidence of 2.6% of SCI patients being treated at the hospital. The aetiology of volvulus is multifactorial and in these patients may be related to: neurological deficit; constipation as a result of immobility; and medications used for controlling muscle spasm, bladder and bowel function. Symptoms and signs are modified by the neurological deficit and awareness of the altered presentation will prevent delay and missed diagnoses. The effect of spinal cord injury and drugs on colonic motility needs further evaluation.

Aged↗

Three views on faculty tenure in medical schools.

Three distinguished academicians share their thoughts on tenure and its future in academic medicine. Paul J. Friedman, from the University of California, San Diego, School of Medicine, explains and defends tenure as practiced in medical schools. He examines the question of giving tenure to clinical faculty, explains posttenure academic review, reports that the impending end of mandatory retirement will not have a significant effect on faculty turnover, and suggests that medical schools make the status of emeritus faculty more attractive. Next, Gail H. Cassell, from the University of Alabama School of Medicine, examines various beliefs about tenure and tenured faculty in the light of available studies, and concludes that many of the negative "myths" about the effect of tenure (e.g., promoting mediocrity and discouraging productivity) are not borne out by research findings. While she supports tenure, she maintains that better criteria are needed for awarding it; that the evaluation of faculty members' teaching needs much improvement; and that more research on tenure is needed. Finally, Richard A. Cooper, from the Medical College of Wisconsin, states that tenure should not continue, because the purposes of tenure (e.g., ensuring freedom of expression; providing long-term financial security and stability) should be and can be accomplished in other ways for all faculty, not just tenured faculty. A different system is needed, one that respects the value of all faculty, that responds to their diverse objectives, is fiscally responsible, and fosters the continuing culture and vitality of medical schools.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude↗

Third ventriculostomy for shunt infections in children.

Four children with extracranial shunts for noncommunicating hydrocephalus suffered from recurrent or intractable shunt infections. All patients were resistant to or relapsed after treatment with intravenous and intrathecal antibiotics with change of the shunt apparatus. They were treated with neuroendoscopic third ventriculostomy and the removal of all implants, except for a reservoir in one patient. That child later had the reservoir removed because of persistent proteus infection. All patients received antibiotics for approximately 2 weeks after the operation. There was no morbidity associated with the procedure, and all patients remain shunt independent with follow-up periods of 21 to 46 months (mean, 33 mo), although one has needed another third ventriculostomy. We have shown that third ventriculostomy is a successful surgical intervention for the management of shunt infections in patients with noncommunicating hydrocephalus.

Cerebrospinal Fluid Shunts↗

Chemical carcinogenesis of the urinary bladder--a status report.

Cigarette smoking and certain types of occupational exposure to arylamines appear to be the main cause of human urinary bladder cancer. Little is known of the promotion of bladder cancer in humans, although this stage has been demonstrated in rodents. Perhaps as a consequence of initiation, multifactorial alterations of cellular genes occur. These genes include the epidermal growth factor receptor gene, erbB-2, int-2, hst, and H-ras, which exert positive control over cell growth, as well as the suppressor genes Rb-1, and the gene coding for p53. Chromosomal changes such as deletions, translocations and/or amplifications related to these genes may be of significance for prognosis of this disease.

Animals↗

Early-retirement incentive programs for medical school faculty.

The Association of American Medical Colleges surveyed the principal business officers of all 126 accredited U.S. medical schools in late 1991 in order to learn about their retirement benefit programs for faculty and whether early-retirement incentive programs were being used. A total of 115 of the schools provided usable responses, which the author reports for all schools, public schools, and private schools. For all schools, defined-contribution plans (based on employer's and employee's contributions plus investment earnings) were the preferred type of retirement benefit program (77%, or 89, of the responding schools). Defined-benefit plans (based on a formula that uses variables of age at retirement, years of service, and salary) were available at 37% (43) of the schools. Early-retirement incentive programs had been used by 70% of the responding schools in the five-year period 1987-1991. Sixteen schools provided descriptions of their formal early-retirement programs, which are summarized. The author observes that, although nearly three-fourths of the responding schools are familiar with the use of the incentive programs, these programs have resulted in few actual early retirements. He discusses why this may be true and compares the pros and cons of formal and ad hoc programs. He concludes that no single program can be considered best; each institution must work with its faculty to design programs to meet institutional goals and faculty interests.

Faculty, Medical↗