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Biomedical subjects

J C Bell

Publications and source records attributed to J C Bell.

At least 73 records · Page 4Linked to original sources

Abelson transformed fibroblasts lacking the EGF receptor are not tumourigenic in nude mice.

Cells transformed by the v-abl-oncogene produce large amounts of the tumour growth factor alpha TGF. alpha TGF is homologous to the epidermal growth factor (EGF) and stimulates cell growth via the EGF receptor pathway. To separate metabolic events in the v-abl-transformed cells mediated by alpha TGF as opposed to the v-abl-encoded protein-tyrosine kinase, we have employed the Swiss 3T3 variant cell line NR6 which lacks a functional EGF receptor. v-abl was found to transform efficiently NR6 cells in vitro. These transformed NR6 cells displayed a variety of in vitro properties which were indistinguishable from transformed wild-type fibroblast lines. However, in contrast to the wild-type lines, v-abl-transformed NR6 cells failed to form tumours when injected into athymic nude mice. These results imply an important function for alpha TGF and the EGF receptor in the establishment of the v-abl-induced fibrosarcomas.

Abelson murine leukemia virus↗

Lineage-specific transformation after differentiation of multipotential murine stem cells containing a human oncogene.

We transfected the human EJ bladder carcinoma oncogene (Ha-rasEJ-1) into multipotential embryonal carcinoma cell line P19. The transgenic P19(ras+) cells expressed high levels of both the mRNA and the p21EJ protein derived from the oncogene. When cultured in the presence of retinoic acid, P19(ras+) cells differentiated and developed into the same spectrum of differentiated cell types as the parental P19 cells (namely, neurons, astrocytes, and fibroblast-like cells). Thus, it seems unlikely that the Ha-ras-1 proto-oncogene product plays a role in initiation of differentiation or in the choice of differentiated cell lineage. Most of the P19(ras+)-derived differentiated cells contained relatively low levels of p21EJ and were nontransformed, whereas certain cells with fibroblast-like morphology continued to express the Ha-rasEJ-1 gene at high levels and were transformed (i.e., immortal and anchorage independent). Fibroblasts derived from P19 cells did not become transformed following transfection of the Ha-rasEJ-1 oncogene, suggesting that transformation of the fibroblast cells only occurred if the oncogene was present and expressed during the early stages of the developmental lineage.

Animals↗

Phosphorylation sites on phosphoprotein NS of vesicular stomatitis virus.

The phosphoprotein NS of vesicular stomatitis virus which accumulates within the infected cell cytoplasm is phosphorylated at multiple serine and threonine residues (G. M. Clinton and A. S. Huang, Virology 108:510-514, 1981; Hsu et al., J. Virol. 43:104-112, 1982). Using incomplete chemical cleavage at tryptophan residues, we mapped the major phosphorylation sites to the amino-terminal half of the protein. Analysis of phosphate-labeled tryptic peptides suggests that essentially all of the label is within the large trypsin-resistant fragment predicted from the sequence of Gallione et al. (J. Virol. 39:52-529, 1981). A similar result has been obtained for NS protein isolated from the virus particle by C.-H. Hsu and D. W. Kingsbury (J. Biol. Chem., in press). Analysis of phosphodipeptides utilizing the procedures of C. E. Jones and M. O. J. Olson (Int. J. Pept. Protein Res. 16:135-142, 1980) enabled us to detect as many as six distinct phosphate-containing dipeptides. From these studies, together with the known sequence data, we conclude that the major phosphate residues on cytoplasmic NS protein are located in the amino third of the NS molecule and most probably between residues 35 and 106, inclusive. The studies also provide formal chemical proof that NS protein has a structure consistent with a monomer of the sequence of Gallione et al. as modified by J. K. Rose (personal communication). The low electrophoretic mobility of this protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis is not therefore due to dimerization.

Hydrolysis↗

Protein kinase activity associated with immunoprecipitates of the vesicular stomatitis virus phosphoprotein NS.

Monospecific antisera prepared to denatured N and NS proteins of the Indiana serotype of VSV were used to investigate the protein associations in extracts of virus-infected cells. Complexes precipitated from the cytoplasm of infected cells with either anti-N or anti-NS serum both contained N and NS proteins but could be differentiated by the absence of any trace of M protein in the complexes precipitated with anti-NS serum. Immunoprecipitation with anti-NS serum of NS protein from the soluble cytoplasmic protein pool always resulted in coprecipitation of N protein suggesting a possible functional association of these proteins in the soluble fraction. The association of protein kinase activity with complexes containing NS protein was demonstrated by the phosphorylation of NS serine residues when immunoprecipitates containing NS protein were incubated with [32P]ATP in vitro. In protein aggregates precipitated with antibody after high salt dissociation of viral proteins it was also possible to demonstrate the presence of a c-src-like protein kinase activity as previously shown by G.M. Clinton, N.G. Guerina, H. Guo, and H.S. Huang (J. Biol. Chem. 257, 3313-3319 (1982) ).

Animals↗

Control of zoonoses in Britain: past, present, and future.

In the past zoonoses that caused serious human illness also caused serious loss of animal production, but there is growing awareness of the public health problems arising from infections that cause little or no such loss. Much can be learnt from the history of the control of bovine tuberculosis and brucellosis. In both cases there was reluctance to accept that animals were the principal cause of infection, and the earliest attempts at control failed because measures were taken only against clinical cases of the disease. The essential features in control of both infections were: official recognition of a problem, willingness of governments to allocate resources, and cooperation between the medical and veterinary professions. Salmonellosis is the most important zoonotic infection in Britain today, though several Orders have reduced the reservoir of infection in food animals. It is suggested that a national team of doctors should be set up to investigate and control zoonoses, that this team should be answerable to a central agency, and that it should build up close working relationships with the nominated officers of the veterinary profession.

Animals↗

Influenza vaccination.

Cost-effectiveness analysis was used to evaluate influenza vaccination. From 1971-1972 through 1977-1978, vaccination of an elderly person 65 years of age or older saved net medical care costs while improving health. Vaccination of younger high-risk adults aged 15 through 64 years also improved health for a low net cost per year of healthy life gained. By covering influenza vaccination during those years, the Medicare program would have incurred a net cost for each vaccination of $13 per year of healthy life gained for medical costs connected with influenza and $791 per year gained including costs of treating other illnesses in later life. The analysis indicates the need for epidemiologic research on the extent of influenza and the mechanism of its spread. The results also raise the issue of public policy to promote influenza vaccination among high-risk persons as a low-cost, preventive technology.

Adolescent↗

Salmonella infection in horses in England and Wales, 1973 to 1979.

During the period 1973 to 1979 the number of recorded incidents of equine salmonellosis increased from 23 in 1973 to a peak of 111 incidents in 1976, but has since decreased to 32 in 1979. Of the 416 incidents recorded during the period of the survey 292 were caused by Salmonella typhimurium and 121 by 33 different serotypes; in three instances rough strains of salmonella were involved. The number of incidents caused by serotypes other than S typhimurium increased from one in 1973 to 32 in 1976. The number of different salmonella serotypes increased from two in 1973 to 23 in 1977 and has subsequently declined. Drug resistance monitoring of salmonella strains from horses showed that most of the strains were resistant to streptomycin and sulphonamides, although resistance to other antibacterial drugs used was low. Seventeen different patterns of antibiotic resistance were observed but resistance to more than two antibiotics was uncommon.

Animals↗

Cost effectiveness of vaccination against pneumococcal pneumonia.

We used cost-effectiveness analysis to examine the medical-care costs of vaccination against pneumococcal pneumonia in relation to its effects on health. Vaccination could add a year of healthy life among all age groups for about $4,800 in net medical-care costs. Cost-effectiveness ratios vary according to the age of the person vaccinated--from $1,000 per year of healthy life for an adult 65 years old or older to $77,000 per year of healthy life for a child between the ages of two and four. These ratios may change substantially with variations in such factors as the cost of vaccination, the duration of immunity, the efficacy and composition of the vaccine, and the percentage of pneumonia that is pneumococcal. This analysis has particular relevance for the Medicare program, since present legislation excludes coverage of most immunizations and other preventive services. Provision of pneumococcal vaccine to the elderly and inclusion of the vaccine as a Medicare benefit merit serious consideration.

Adolescent↗

Proteins of vesicular stomatitis virus. V. Identification of a precursor to the phosphoprotein of Piry virus.

A metabolic precursor to the major phosphoprotein of Piry virus (NSv) has been identified in extracts of Piry virus-infected L cells. The conversion of the precursor NSi to NSv occurs with a half-life of 20 min and is independent of continued protein synthesis. NSi has a greater electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than does the product NSv, suggesting an increase in molecular weight during maturation. The conversion is unaffected by cyclic AMP, cyclic GMP, or by theophilline and cordycepin. No decrease in isoelectric point of NSv relative to NSi was observed on isoelectric focusing acrylamide gels. These latter observations suggest that NSi and NSv do not differ in extent of phosphorylation. We also report, without further characterization, the identification of another phosphoprotein in Piry virus-infected cells having an electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis just slightly greater than the nucleocapsid N protein.

L Cells↗

Switching from competition to sharing or cooperation at large response requirements: competition requires more responding.

Two pairs of high-school students matched-to-sample for money. On each trial, a subject could either respond on one lever to take the matching-to-sample problem himself (taking response) or respond on a second lever to give the problem to his coactor (giving response). The first subject to complete the response requirement determined the distribution of the problem. Competition maximizes the amount of responding over trials, i.e., both subjects make taking responses on each trial. Sharing and cooperation minimize responding: only one subject makes a taking response (sharing) or a giving response (cooperation) on each trial, and the subjects alternate responding such that there is an equitable distribution of responses and reinforcers over trials. Large increases in the fixed-ratio response requirement to distribute problems produced: (1) a switch from competition to sharing or cooperation, (2) the expected concomitant change from inequitable to equitable distributions of reinforcers, and (3) a reduction in the amount of responding for three of the four subjects. Previous animal research has shown that large response requirements may have aversive properties. Switching from competition to sharing or cooperation at large response requirements allows a reduction in responding and, at the same time, a moderate number of reinforcers for each subject.

Journal Article↗

Abelson-transformed fibroblasts contain nuclear phosphotyrosyl-proteins which preferentially bind to murine DNA.

Protein-tyrosine kinases, either in the form of growth-factor receptors or as the polypeptide products of oncogenes, appear to be important in the regulation of cell growth and transformation. A major question, however, is how their substrates mediate changes in gene expression (reviewed in refs 6-8). Because binding of proteins to specific DNA sequences represents the most direct mechanism for regulating transcription, we have investigated the possibility that some DNA-binding proteins may be substrates of protein-tyrosine kinases. Here, we present evidence for nuclear phosphotyrosyl-proteins in murine fibroblasts transformed by the v-abl protein-tyrosine kinase. Furthermore, we have found that these proteins are not significantly phosphorylated in normal NIH 3T3 cells. Finally, using affinity competition chromatography with bacterial and mouse DNA, we have demonstrated that some of these proteins preferentially bind to mouse DNA. The identification of phosphotyrosyl-proteins with selective DNA-binding properties suggests a possible mechanism through which protein-tyrosine kinases may effect changes in gene transcription.

Abelson murine leukemia virus↗