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Biomedical subjects

J Field

Publications and source records attributed to J Field.

At least 19 recordsLinked to original sources
PubMed1996

Definition of a tumor suppressor gene locus on the short arm of chromosome 3 in squamous cell carcinoma of the head and neck by means of microsatellite markers.

BACKGROUND: Tumor suppressor genes are important in the development of head and neck cancer. Using microsatellite markers that map close to the region 3p24-pter, we determined the frequency of allele loss close to this site with a view to narrowing the search for a putative tumor suppressor gene involved in the development of squamous cell carcinoma of the head and neck, which may facilitate future positional cloning techniques. DESIGN: Laboratory-based project with tumor and normal specimens subjected to molecular genetic analysis. Tumor-normal tissue DNA pairs were analyzed for allelic imbalance and microsatellite instability on chromosome 3p in the region 3p24-pter by the polymerase chain reaction and microsatellite markers D3S1304, D3S656, D3S1252, D3S1293, THRB, and D3S1266. SETTING: Molecular genetics and oncology research laboratory. PATIENTS: Paired tumor-normal DNA samples were obtained from 46 patients with tumors of the head and neck. MAIN OUTCOME MEASURES: Detection of loss of heterozygosity and microsatellite instability on chromosome 3 in the region 3p24-p25.1. RESULTS: We found loss of heterozygosity with at least one marker in 48% of informative cases and loss of heterozygosity or microsatellite instability in 57% of informative cases. The minimal region of loss was found in the region bounded by D3S656 and D31293. CONCLUSION: A putative tumor suppressor gene in head and neck cancer lies between D3S656 and D3S1293 in the 3p25.1 region.

Alleles↗
PubMed1996

Impaired bile flow and disordered hepatic calcium homeostasis are early features of halothane-induced liver injury in guinea pigs.

To characterize the early events in liver injury produced by halothane, experiments were performed in genetically susceptible guinea pigs 19 hours after halothane exposure. Serum bile acid concentrations were fourfold increased in halothane-exposed animals compared with controls. In isolated perfused liver experiments, livers from halothane-exposed animals did not differ in hepatic oxygen uptake or in perfusion pressure at the end of experiments, but bile flow and biliary bile salt concentrations were reduced. Hepatic calcium content was increased in halothane-exposed guinea pigs compared with controls, and further experiments were performed to explore the reason for this. As determined by infusion of 45Ca to steady-state perfusate concentrations, hepatic calcium clearance was increased in halothane-exposed guinea pigs compared with controls (0.37 +/- 0.06 vs. 0.28 +/- 0.02 mL/min, P < .01). Decreased biliary excretion of calcium was also noted and was entirely attributable to reduced bile flow. However, although decreased excretion contributed to hepatic accumulation of calcium, it was quantitatively less important than enhanced hepatic uptake. As indicated by passage of a bolus of horseradish peroxidase from perfusate into bile, hepatic tight junction permeability was increased five-fold after halothane exposure. It is concluded that cholestasis, as exemplified by reduced bile flow, is an early feature of the liver injury produced by halothane in guinea pigs and is associated with increased tight junction permeability. Although the decrease in bile flow contributes to an early increase in hepatic calcium content, entry of calcium from the perfusion compartment is quantitatively more important.

Animals↗
PubMed1996

A conserved proline-rich region of the Saccharomyces cerevisiae cyclase-associated protein binds SH3 domains and modulates cytoskeletal localization.

Saccharomyces cerevisiae cyclase-associated protein (CAP or Srv2p) is multifunctional. The N-terminal third of CAP binds to adenylyl cyclase and has been implicated in adenylyl cyclase activation in vivo. The widely conserved C-terminal domain of CAP binds to monomeric actin and serves an important cytoskeletal regulatory function in vivo. In addition, all CAP homologs contain a centrally located proline-rich region which has no previously identified function. Recently, SH3 (Src homology 3) domains were shown to bind to proline-rich regions of proteins. Here we report that the proline-rich region of CAP is recognized by the SH3 domains of several proteins, including the yeast actin-associated protein Abp1p. Immunolocalization experiments demonstrate that CAP colocalizes with cortical actin-containing structures in vivo and that a region of CAP containing the SH3 domain binding site is required for this localization. We also demonstrate that the SH3 domain of yeast Abp1p and that of the yeast RAS protein guanine nucleotide exchange factor Cdc25p complex with adenylyl cyclase in vitro. Interestingly, the binding of the Cdc25p SH3 domain is not mediated by CAP and therefore may involve direct binding to adenylyl cyclase or to an unidentified protein which complexes with adenylyl cyclase. We also found that CAP homologous from Schizosaccharomyces pombe and humans bind SH3 domains. The human protein binds most strongly to the SH3 domain from the abl proto-oncogene. These observations identify CAP as an SH3 domain-binding protein and suggest that CAP mediates interactions between SH3 domain proteins and monomeric actin.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Provision of sex education and early sexual experience: the relation examined.

OBJECTIVES: To explore the relation between receipt of sex education and experience of first intercourse. SUBJECTS AND DESIGN: The national survey of sexual attitudes and lifestyles is based on a sample of 18,876 respondents aged 16-59, randomly selected from the Post Office's small-user postcode address file. Data were collected between May 1990 and November 1991 by personal interviews combining a self administered questionnaire with a face to face interview. MAIN OUTCOME MEASURES: Age at first intercourse, use of contraception at first intercourse, actual and preferred source of sex education (including school based lessons). RESULTS: Median age at first intercourse fell by four years for women and three years for men over the past four decades, to 17 for both men and women aged 16-19 at the time of interview. Of those respondents for whom school was the main source of information about sexual matters, men were less likely, and women no more likely, to have had intercourse before the age of 16 than were those citing other main sources, such as friends and the media. Both men and women were more likely to have used some method of contraception. In multivariate analysis, these effects remained after controlling for the effect of current age, educational attainment, and religious affiliation. CONCLUSIONS: These data provide no evidence to support the concern that provision of school sex education might hasten the onset of sexual experience. These findings have important implications for the provision of sexual health education and highlight the need to carry out prospective and randomised studies of the impact of sex education.

Adolescent↗
PubMed1995

An actin monomer binding activity localizes to the carboxyl-terminal half of the Saccharomyces cerevisiae cyclase-associated protein.

The Saccharomyces cerevisiae adenylyl cyclase complex contains at least two subunits, a 200-kDa catalytic subunit and a 70-kDa cyclase-associated protein, CAP (also called Srv2p). Genetic studies suggested two roles for CAP, one as a positive regulator of cAMP levels in yeast and a second role as a cytoskeletal regulator. We present evidence showing that CAP sequesters monomeric actin (Kd in the range of 0.5-5 microM), decreasing actin incorporation into actin filaments. Anti-CAP monoclonal antibodies co-immunoprecipitate a protein with a molecular size of about 46 kDa. When CAP was purified from yeast using an anti-CAP monoclonal antibody column, the 46-kDa protein co-purified with a stoichiometry of about 1:1 with CAP. Western blots identified the 46-kDa protein as yeast actin. CAP also bound to muscle actin in vitro in immunoprecipitation assays and falling ball viscometry assays. Experiments with pyrene-labeled actin demonstrated that CAP sequesters actin monomers. The actin monomer binding activity is localized to the carboxyl-terminal half of CAP. Together, these data suggest that yeast CAP regulates the yeast cytoskeleton by sequestering actin monomers.

Actins↗
PubMed1995

The design of biplanar, shielded, minimum energy, or minimum power pulsed B0 coils.

By extending the formalism previously developed for the design of unshielded, biplanar gradient coils, shielded biplanar B0 coils optimized for homogeneity and either minimum energy or minimum power may be designed. We present results from an integrated approach to shielded biplanar coil design, the results of which are also applicable to gradient coils, enabling the design of shielded coils with a concomitant decrease in total inductance of the coil. Length constraints are also included in the integrated minimization procedure. Results from a preliminary design indicate that high-homogeneity, low-impedance, well-shielded coils result from this design approach.

Electronics↗
PubMed1995

Antipyrine clearance and response to interferon treatment in patients with chronic active hepatitis C.

To determine whether hepatic metabolic function affects the response to interferon treatment, we measured antipyrine clearance (APC) in 85 patients with chronic active hepatitis C and compared the results with treatment outcome. Among 55 patients who responded to interferon by normalization of alanine transaminase (ALT), median APC before treatment was 0.47 (range, 0.12 to 0.98; normal range, 0.34 to 1.02 mL/min/kg body wt), a value that was significantly greater than in 30 nonresponders (0.23; 0.08 to 0.67 mL/min/kg body wt, P < .001). APC was closely associated with response to interferon. The response rate among cases with values > 0.25 mL/min/kg body weight was 79%, the same as in cases without cirrhosis. Cases without cirrhosis and with APC of > 0.25 mL/min/kg body weight had an 85% chance of responding to interferon; this was unlikely a simple reflection of histological activity, because the correlation with Scheuer score was poor in this subgroup (r = -.31, P < .05). A second, independent group of 43 patients was used to test the predictive value of APC (using 0.25 mL/min/kg body wt as a cut-off) for response to interferon treatment. In this group, APC correctly predicted positive response to interferon in 75% of cases. APC was also used to measure the effects of treatment on hepatic metabolic function. Regardless of outcome, there was no change in APC at the end of a 6-month course of interferon treatment. Six months later, however, improvement in APC (14%; P < .05) was evident among responders but not in those who had failed to respond to interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Sexual behaviour and HIV epidemiology: comparative analysis in France and Britain. The ACSF Group.

OBJECTIVE: France and Britain have similar size populations, yet the incidence of AIDS is threefold higher in France. The objective of this study was to compare data from two surveys recently performed in the two countries, in order to determine whether differences in sexual and drug-use behaviour could explain the different epidemiological patterns. DESIGN: Cross-sectional random sample surveys of France and Britain. RESPONDENTS: In France, 20,055 persons aged 18-69 years and in Britain, 18,876 persons aged 16-59 years were interviewed in 1990-1991. The following indicators were compared in the respondents aged 18-59 years: prevalence of homosexual experience and injecting drug use, number of sexual partners, prevalence of sexual practices, condom use and sex with prostitutes, age of sexual partners. RESULTS: Very similar results were found for the prevalence of male homosexual partnerships. Slightly higher numbers of lifetime partners were reported by French than British men, but no difference was found for recent periods. Anal intercourse and sex with prostitutes was more frequent among heterosexual French people than British people. Condom use was more systematic in Britain than in France. CONCLUSION: Only small differences were found between the two countries, although prevalence of risk indicators were higher in France. These differences combined with early development of prevention policies in Britain, together with the timing of virus introduction, may contribute to differences between the epidemics in the two countries.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Interactions between adenylyl cyclase, CAP and RAS from Saccharomyces cerevisiae.

The adenylyl cyclase complex from Saccharomyces cerevisiae contains at least two subunits, a catalytic subunit of M(r) 200,000, encoded by CYR1 and a cyclase associated subunit, of apparent M(r) 70,000, encoded by CAP. The complex is a major effector of RAS proteins in S. cerevisiae. The interactions between CAP, adenylyl cyclase and RAS were explored in a strain of yeast that lacked CAP and contained an epitope tagged adenylyl cyclase. Adenylyl cyclase activity in this strain was not immunoprecipitated with anti-CAP antibodies, but was immunoprecipitated with anti-epitope antibodies. Two anti-CAP polyclonal antisera and five anti-CAP monoclonal antibodies were used in these studies. Like CAP-bound adenylyl cyclase, the CAP-free adenylyl cyclase was fully activated by yeast RAS2. Transformation of cap strains with plasmids expressing portions of CAP allowed the adenylyl cyclase binding sites on CAP to be mapped by immunoprecipitation experiments. In other experiments, deletion mutations of adenylyl cyclase were used to map the CAP binding site on adenylyl cyclase. The adenylyl cyclase binding site localized to the amino one third of CAP (amino acids 1-168), and the CAP binding site localized to the carboxyl terminus of adenylyl cyclase (amino acids 1768-2026).

Adaptor Proteins, Signal Transducing↗
PubMed1994

Algodystrophy after Colles fractures is associated with secondary tightness of casts.

We describe a direct method of measuring the tightness of plaster casts. Tightness was measured weekly in 23 consecutive patients with Colles' fractures. Six had objective signs of algodystrophy nine weeks after the fracture. In these patients the plaster cast was significantly tighter during the first three weeks than in patients who did not develop algodystrophy. The complex relationship between these findings is discussed.

Adult↗
PubMed1993

Audit of outcome of long-term enteral nutrition by percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) is the preferred method for administration of long-term enteral tube feeding. However, most published studies describe only short-term follow-up in any detail. We report the long-term outcome and complication rate after PEG insertion in 49 patients (mean [SE] age 64 [2] years) whose mean length of PEG feeding was 175 days (range 30-560). Data were collected prospectively. PEG insertion was technically successful in all cases, with a procedure-related mortality of 2%. Early (< 30 days) mortality and morbidity were 8% and 22%, respectively. Of 45 patients surviving for more than 30 days, 76% were able to return home and 6 patients were eventually able to revert to oral feeding. There were 27 late complications: 2 site infections, 17 mechanical problems, and 8 episodes of gastrointestinal dysfunction. 51% of patients had no problems at all and 22% had 2 or more complications. 47% of complications required a hospital visit for resolution. Long-term enteral feeding by PEG was safe, effective, and had a low complication rate. Our patients were managed by a specialist nutrition team, a policy that may reduce the complication rate and hospital visits for patients being fed at home, and allow early discharge of dysphagic patients, thereby reducing costs.

Aged↗