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Biomedical subjects

J R Jenkins

Publications and source records attributed to J R Jenkins.

At least 19 recordsLinked to original sources
PubMed1992

The E2 binding sites determine the efficiency of replication for the origin of human papillomavirus type 18.

Human papillomaviruses (HPV-s) have been shown to possess transforming and immortalizing activity for many different, mainly keratinocyte cell lines and they have been detected in 90% of anogenital cancer tissues, which suggests a causative role in the induction of anogenital and other tumours. We have exploited a quantitative assay to identify and characterize the origin of replication of the human papillomavirus type 18 (HPV-18), one of the most prevalent types in the high-risk HPV group. Replication of HPV origin fragments was studied transiently by cotransfection with a protein expression vector providing replication proteins E1 and E2. We have localized the HPV-18 origin to nucleotides 7767-119. This region contains three E2 binding sites and an essential A/T rich DNA region (nucleotides 9-35) that is partly homologous to the E1 binding site found in bovine papillomavirus type 1 (BPV-1) genome. At least one of the three E2 binding sites was absolutely required for origin function; addition of other E2 sites had cooperative stimulating effect. This is the first quantitative analysis of the E2 binding sites for papillomavirus replication.

Base Sequence↗
PubMed1992

Isolation of cDNA clones encoding the beta isozyme of human DNA topoisomerase II and localisation of the gene to chromosome 3p24.

Topoisomerases catalyse the interconversion of topological isomers of DNA and have key roles in nucleic acid metabolism. Human cells express two distinct type II topoisomerase isozymes, designated topoisomerase II alpha (170 kDa form) and topoisomerase II beta (180 kDa form). We have isolated cDNA clones encoding the beta isozyme from a human B-cell library. The proposed coding region for the topoisomerase II beta protein is 4,863 nucleotides long and would encode a polypeptide with a calculated M(r) of 182,705. The predicted topoisomerase II beta protein sequence shows striking similarity (72% identical residues) to that of the human alpha isozyme, and homology to topoisomerase II proteins from Drosophila, yeast and bacteria. Regions of greatest amino acid sequence divergence lie at the extreme N-terminus and over a C-terminal domain comprising approximately 25% of the total protein. We have quantified the level of topoisomerase II beta mRNA in a panel of human tumour cell lines of different origin using an RNase protection assay, and compared the level to that of topoisomerase II alpha mRNA. Topoisomerase II beta mRNA was expressed in haemopoietic, epithelial and fibroblast cell lines, although to different extents, with U937 cells (promonocytic leukaemia) showing a particularly high level. There was no obvious relationship in terms of level of expression between the topoisomerase II alpha and beta genes. We have localised the gene encoding topoisomerase II beta protein to chromosome 3p24 in the human genome.

Amino Acid Sequence↗
PubMed1992

Specialized instruction within general education: a case study of one elementary school.

This study examined how classroom teachers in one elementary school approached the problem of designing specialized instruction for students with reading problems. We asked 12 teachers to rate their confidence in designing effective interventions and then to diagnose a student's reading problem, select an intervention, and implement it. Teachers were moderately confident about their ability to design effective interventions; but some teachers expressed doubts about how to proceed. Their approach to intervention differed somewhat from that of special education resource teachers. Some teachers experienced considerable difficulty in implementing the interventions they selected.

Achievement↗
PubMed1992

A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization.

The p53 gene product has been implicated in both human and animal tumorigenesis. p53 forms heterologous complexes with the transforming proteins encoded by several different DNA tumor viruses. p53 also assembles into stable homo-oligomers. We demonstrate that the major structural determinant for the tetramerization of p53 is an alpha-helical plus basic region motif near the C-terminus of the protein. A monomeric p53 mutant adopts a conformation distinct from both 'wild-type' and 'mutant' form as defined by PAb1620 and PAb240 monoclonal antibody recognition. Nevertheless, monomeric and dimeric mutant p53 proteins retain the ability to suppress SV40 origin-directed DNA replication in vivo. Thus, p53-p53 interaction and expression of the PAb1620 epitope is not a prerequisite for such activity. We present data suggesting that suppression of replication by p53 may occur by a mechanism that is independent of detectable p53-T antigen association.

Amino Acid Sequence↗
PubMed1991

Effect of preschool integration for children with disabilities.

This study examined the effects of integration and segregation in a special education preschool program for children with mild to moderate disabilities to determine whether initial level of development differentially influenced gains achieved. No main-effect differences between the two groups appeared on several pretest and posttest measures. Aptitude-by-Treatment analyses revealed than higher performing students gained more from integrated classes, whereas lower performing students gained more from segregated classes. The data suggest careful monitoring of lower functioning students to ensure appropriate academic and social stimulation.

Child↗
PubMed1991

Development of a school building model for educating students with handicaps and at-risk students in general education classrooms.

This study, conducted in the context of a 4-year project to redesign special and remedial services in an elementary school, examined the effects of cooperative learning, cross-age tutoring, and in-class services for students with handicaps and remedial students. All students (524) in Grades 1 through 6 in two medium-sized elementary schools took part in the study. All three treatments were introduced into one of the schools, with the second school serving as a control. The cooperative learning treatment was delivered to all sixth-grade students, cross-age tutoring to special and remedial students in Grades 1 through 3, and the in-class services to all grade levels. Results indicated that, although the character of the instructional services changed markedly, none of the three treatments had much impact on achievement. Reasons for the findings are explored.

Achievement↗
PubMed1991

Endogenous HeLa p53 proteins are easily detected in HeLa cells transfected with mouse deletion mutant p53 gene.

It has been reported [Matlashewski et al. (1986). Eur. J. Biochem., 154, 665-672] that HeLa cells contain no detectable p53 protein, although they contain p53 mRNA which is translationally active. Here it is shown that endogenous HeLa p53 proteins were easily detected in HeLa cells transiently expressing mouse deletion mutant p53 gene after transfection with the appropriate recombinant plasmid. This detection was obtained by immunoprecipitation coupled with SDS-PAGE as well as by Western blotting experiments. Our results strongly suggest that HeLa p53 mRNA is actually translated in vivo, generating an extremely unstable p53 protein. Considering that the HeLa cell line is a HPV-18-positive human cervical carcinoma cell line, this high instability of HeLa p53 proteins is in keeping with the finding that E6 oncoprotein encoded by human papillomavirus 16 or 18 promotes the degradation of p53 proteins [Scheffner et al. (1990). Cell, 63, 1129-1136].

Animals↗
PubMed1990

The effect of novobiocin on yeast topoisomerase type II.

Low concentrations of novobiocin are toxic to permeable yeast cells, but do not inhibit type II topoisomerase activity. Furthermore, the enzyme does not bind specifically to novobiocin-Sepharose. These observations are in agreement with genetical analyses. Mutations at a single locus that confer novobiocin resistance and temperature sensitivity exhibit a similar phenotype to cells treated with novobiocin, but are not topoisomerase II mutants.

Chromatography, Affinity↗
PubMed1990

Inhaled PAF fails to induce airway hyperresponsiveness to methacholine in normal human subjects.

The effects of three increasing doses of platelet-activating factor (PAF) on airway caliber and methacholine bronchial responsiveness were studied. On separate occasions nine normal subjects inhaled a single cumulative provocation concentration of methacholine (control) causing a 40% fall (PC40 Vp30) in maximum expiratory flow rate at 70% of base-line vital capacity below total lung capacity during a partial forced expiratory maneuver or 100 or 200 micrograms PAF, and seven subjects inhaled a further dose of 400 micrograms PAF. Methacholine responsiveness was measured before, at 3 and 7 h, then on days 1, 2, 3, 4, 7, 10, and 14 after each challenge. The maximum falls in Vp30 appeared dose dependent, but a significant difference between the magnitude of the responses was only observed between the 400- and 100-micrograms PAF dose (P less than 0.05). During the control period repeated methacholine challenges resulted in a progressive increase in cumulative provocation concentration of an agonist causing a 20% fall in forced expiratory volume in 1 s from base line, reaching significance on days 1 and 2 (2.44- and 2.4-fold of base line, respectively, P less than 0.01) before returning to base line on day 7. No difference was seen in methacholine responsiveness after any of the three doses of PAF compared with that after the control. We conclude that PAF causes dose-dependent bronchoconstriction but does not change airways responsiveness to methacholine and that repeated high-dose methacholine challenge leads to loss of responsiveness to this agonist.

Administration, Inhalation↗
PubMed1990

Special education and the regular education initiative: basic assumptions.

The regular education initiative (REI) is a thoughtful response to identified problems in our system for educating low-performing children, but it is a not a detailed blueprint for changing the system. Educators must achieve consensus on what the REI actually proposes. The authors infer from the REI literature five assumptions regarding the roles and responsibilities of elementary regular classroom teachers, concluding that these teachers and specialists form a partnership, but the classroom teachers are ultimately in charge of the instruction of all children in their classrooms, including those who are not succeeding in the mainstream. A discussion of the target population and of several partnership models further delineates REI issues and concerns.

Child↗
PubMed1990

The F1 ATP synthetase beta-subunit: a major yeast novobiocin binding protein.

Novobiocin affects DNA metabolism in both prokaryotes and eukaryotes, resulting in cell death. In prokaryotes, the drug is a specific inhibitor of DNA gyrase, a type II topoisomerase that can be purified on a novobiocin-Sepharose column. The yeast type II topoisomerase is neither the biochemical, nor the genetic target of the antibiotic. We have purified the major yeast novobiocin binding proteins and identified one of them as the beta-subunit of the yeast mitochondrial F1 ATP synthetase, a protein highly conserved throughout evolution. The inactivation of this protein might explain the toxic effects of novobiocin on higher eukaryotic cells.

Amino Acid Sequence↗
PubMed1990

The p53 nuclear localisation signal is structurally linked to a p34cdc2 kinase motif.

We have identified a region of human p53 protein with striking homology to a sequence motif on Simian Virus 40 T antigen which includes the nuclear localisation signal. Mutation of basic amino acid residues in this region of p53 (residues 312 to 323; SSSPQPKKKP) compromises transport of p53 protein to the nucleus. The sequence functions efficiently as a nuclear localisation signal when fused to E. coli beta galactosidase. Serine 315 within this p53 structural motif is phosphorylated in vitro by the cell cycle kinase p34cdc2. Thus in both T antigen and p53, nuclear localisation signal and p34cdc2 kinase acceptor residue map to a contiguous region of primary amino acid sequence.

Amino Acid Sequence↗
PubMed1990

The effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid (15-HETE) on airway calibre and non-specific responsiveness in normal and asthmatic human subjects.

15-hydroxyeicosatetraenoic acid (15-HETE) is the predominant oxidative metabolite of arachidonic acid in human lung. We have studied its effects on airway calibre and non-specific bronchial responsiveness (NSBR) in eight normal and eight asthmatic subjects. 15-HETE, at doses up to 70 nmol, had no effect on airway calibre in either group of subjects. However, 3 h after its administration, 15-HETE reduced NSBR in the normal subjects (geometric mean methacholine PD40 Vp30 increased by 2.29-fold from baseline compared with a corresponding 1.14-fold increase after diluent, p less than 0.05). Similarly, 4 h after inhaled 15-HETE, the spontaneous increase in NSBR in the asthmatics was completely inhibited (geometric mean histamine PD40 Vp30 decreased significantly to 0.41-fold of baseline after diluent (p less than 0.01) compared with a 1.1-fold increase after 15-HETE, p less than 0.01). These data suggest 15-HETE may play an autacoid role in airway function.

Administration, Inhalation↗
PubMed1989

Ability of p53 and the adenovirus E1b 58-kilodalton protein to form a complex is determined by p53.

We have investigated p53-E1b 58-kilodalton (kDa) protein complex formation during permissive and semipermissive infections with adenovirus type 5 (Ad5) dl309. While metabolic labeling studies easily detected p53-E1b 58-kDa protein complexes in transformed rat cells (XhoI-C), the same methods have not revealed complexes during infection of either human osteosarcoma cells (permissive) or normal rat kidney cells (semipermissive). Complexes were not detectable at any stage during the replicative cycle of Ad5 dl309 in osteosarcoma cells, and they could not be stabilized by using an in vivo cross-linking agent. In addition, using the E4-defective mutant Ad5 dl355, no complexes were observed either. Thus, the lack of p53-E1b 58-kDa protein complex formation during infection is not due to competition from the E4 34-kDa protein. In vitro association experiments showed that in vitro-translated mouse and human p53 could form complexes with E1b 58-kDa antigen expressed during infection. Thus, such E1b proteins are competent to form complexes. The converse experiment, in which in vitro-translated E1b 58-kDa protein was mixed with lysates of osteosarcoma cells, showed little or no p53-E1b 58-kDa protein association, even though the in vitro E1b 58-kDa protein could associate stably with p53 from cells containing endogenous p53-E1b 58-kDa protein complex. These data suggest that competence to form p53-E1b 58-kDa protein complexes resides in some property of p53.

Adenovirus Early Proteins↗
PubMed1989

Effects of social integration on preschool children with handicaps.

This study examined the effects of (a) integrating handicapped and nonhandicapped children in preschools and (b) a condition designed to promote social integration. Fifty-six children with mild and moderate handicaps were randomly assigned to four experimental conditions: integrated/social interaction, integrated/child-directed, segregated/social interaction, and segregated/child-directed. Observation revealed a higher proportion of interactive play, as well as higher language development, in the social interaction conditions; and children in the integrated/social interaction condition received significantly higher ratings of social competence. These data suggest that structuring social interaction between higher and lower performing children can result in benefits to the lower performing students.

Child, Preschool↗