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Biomedical subjects

J R Jenkins

Publications and source records attributed to J R Jenkins.

89 records · Page 5Linked to original sources

General surgical pre-admission clinic.

Ninety-nine patients from a non-urgent general surgical waiting list were randomly selected for either direct admission to a hospital bed or review at a preadmission clinic. A considerable reduction in subsequent bed occupancy was shown in the latter group. The findings suggest that more detailed review of patients in the outpatient department would result in the more efficient use of hospital facilities.

Appointments and Schedules↗

The omnipotent suppressor SUP45 affects nucleic acid metabolism and mitochondrial structure.

Yeast (Saccharomyces cerevisiae) strains sensitive to a variety of drugs were used to select for novobiocin-resistant mutants that were simultaneously temperature-sensitive. The mutants remained as sensitive as the parent strains to a wide range of drugs other than novobiocin, and did not exhibit any suppression of suppressible auxotrophic markers. At the non-permissive temperature, the mutant cells arrested mainly as unbudded cells, and were instantly defective in DNA and RNA synthesis, but not protein synthesis. The cloned wild-type gene was identified as SUP45, which has been previously implicated in the translation process. Our results suggest that SUP45 may have a function in addition to, or different from, the one that has been assigned to it previously.

Cloning, Molecular↗

Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53.

Malignant transformation of primary cells requires at least two distinct and characteristic alterations in cellular behaviour. The first, cellular immortality, can be induced by chemical carcinogens or by cloned oncogenes such as polyoma large T (ref. 4), adenovirus early region 1A (E1A) or the oncogene from avian (MC29) myelocytomatosis virus, v-myc. Cells whose in vitro life-span has been extended by these procedures can be fully transformed by transfection with oncogenes belonging to a different complementation group, including genes of the ras family, adenovirus E1b and polyoma virus middle T (refs 4, 5). The unstable cellular phosphoprotein p53 is frequently present at elevated levels in transformed cells and is stabilized by the formation of complexes with simian virus 40 (SV40) large T or adenovirus E1b 57K protein. Although several reports have associated p53 with cell proliferation, its role remains obscure. We have cloned complementary DNA sequences encoding murine p53 and report here that transfection of p53 expression constructs into cells of finite lifespan in vitro results in cellular immortality and susceptibility to transformation by a ras oncogene.

Animals↗

The cellular oncogene p53 can be activated by mutagenesis.

P53 is a cellular phosphoprotein of short half-life (t1/2) which is present at elevated levels in cells transformed by various stimuli including viruses, chemicals and radiation. p53 forms specific stable complexes with simian virus 40 (SV40) large-T antigen and an adenovirus E1b protein of relative molecular mass (Mr) 57,000. A number of reports have associated p53 with cell proliferation, and p53 complementary DNA expression constructs immortalize primary cells in vitro and render them sensitive to transformation by an activated ras oncogene. We have examined the biological properties of a set of p53 expression constructs, and report here that cellular immortalization by a wild-type p53 cDNA gene is conditional upon the promoter/enhancer construction used, but that p53 can extend cellular lifespan by a second distinct mechanism involving rearrangements of the coding sequence which give rise to stable protein products. Cells immortalized by one of these mutants are refractory to subsequent transformation by a ras oncogene, indicating that cellular immortalization and ras cooperation are separate activities.

Animals↗

Mouse p53 inhibits SV40 origin-dependent DNA replication.

p53 is a cellular phosphoprotein that is present at elevated concentrations in cells transformed by different agents. p53 complementary DNA expression-constructs immortalize primary cells in vitro and co-operate with an activated ras oncogene in malignant transformation. Several reports have implicated p53 in mammalian cell cycle control and specifically with events occurring at the G0-G1 boundary. p53 forms specific complexes with simian virus 40 (SV40) large-T antigen, and such complexes are found associated with both replicating and mature SV40 DNA in lytically infected cells. In an accompanying paper Gannon and Lane report that in in vitro plate-binding assays, mouse p53 can displace polymerase alpha from complex with T-antigen. We have examined the in vivo consequences of expressing wild-type and mutant p53 proteins from other species in SV40-transformed monkey cells. We report here that expression of mouse p53 results in a substantial and selective inhibition of SV40 origin-dependent DNA replication. In addition to any function in the G0-G1 transition, the data presented suggest that p53 may affect directly the initiation or maintenance of replicative DNA synthesis.

Animals↗

Effects of tutoring in phonological and early reading skills on students at risk for reading disabilities.

This study examined the effectiveness of nonprofessional tutors in a phonologically based reading treatment similar to those in which successful reading outcomes have been demonstrated. Participants were 23 first graders at risk for learning disability who received intensive one-to-one tutoring from noncertified tutors for 30 minutes, 4 days a week, for one school year. Tutoring included instruction in phonological skills, letter-sound correspondence, explicit decoding, rime analysis, writing, spelling, and reading phonetically controlled text. At year end, tutored students significantly outperformed untutored control students on measures of reading, spelling, and decoding. Effect sizes ranged from .42 to 1.24. Treatment effects diminished at follow-up at the end of second grade, although tutored students continued to significantly outperform untutored students in decoding and spelling. Findings suggest that phonologically based reading instruction for first graders at risk for learning disability can be delivered by nonteacher tutors. Our discussion addresses the character of reading outcomes associated with tutoring, individual differences in response to treatment, and the infrastructure required for nonprofessional tutoring programs.

Certification↗

Should PAF inhalation challenge be used as an experimental model of bronchial hyperresponsiveness in man?

Present evidence suggests that PAF-induced bronchial hyperresponsiveness (BHR) is a variable phenomenon in man. Even in the responders, the magnitude of change is small and the response is poorly reproducible. Endobronchial biopsy and bronchial lavage studies following inhaled PAF did not show any increase in the number of activation of eosinophils, which are pivotal in the pathogenesis of BHR. Unless and until the characteristics of responders are identifiable, PAF inhalation challenge should not be used as a human model of BHR.

Biopsy↗