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Biomedical subjects

J Field

Publications and source records attributed to J Field.

At least 73 records · Page 4Linked to original sources
PubMed1997

Mandibular invasion in patients with oral and oropharyngeal squamous carcinoma.

Invasion of the mandible in squamous carcinoma of the oral cavity and oropharynx has always proved a problem for head and neck oncologists. We studied 82 patients who had mandibulectomies as part of their primary surgical treatment for cancer of these sites. In 40 patients, the tumour appeared to be invading the mandible on clinical grounds and 33 patients had tumours invading the mandible when the latter was examined histopathologically. Multivariate analysis showed that tumour was more likely to be fixed to and clinically invading the mandible in the presence of cancer of the oral cavity, compared with oropharyngeal cancer (P < 0.0001). There was a high degree of correlation between clinical invasion of the mandible and histopathological invasion of the mandible (P = 0.0059). In addition, clinical invasion of the mandible correlated with radiological findings (P = 0.0284). The 5-year survival of those patients with tumour that appeared not to be invading the mandible was 53% compared with 25% for those where tumour did appear to be invading the mandible (P < 0.02). The sensitivity and specificity of clinical evidence of mandibular invasion was calculated with the final arbiter of invasion being the histopathological findings. The sensitivity of clinical examination was 91% and the specificity 80%. The positive predictive value was 75% and the negative predictive value 93%. Mandibular invasion is a poor prognostic sign in cancer of the oropharynx and oral cavity. Detection of invasion prior to operation is obviously extremely important and it appears that clinical findings are an accurate method of predicting invasion.

Adult↗
PubMed1997

Kinase-deficient Pak1 mutants inhibit Ras transformation of Rat-1 fibroblasts.

Among the mechanisms by which the Ras oncogene induces cellular transformation, Ras activates the mitogen-activated protein kinase (MAPK or ERK) cascade and a related cascade leading to activation of Jun kinase (JNK or SAPK). JNK is additionally regulated by the Ras-related G proteins Rac and Cdc42. Ras also regulates the actin cytoskeleton through an incompletely elucidated Rac-dependent mechanism. A candidate for the physiological effector for both JNK and actin regulation by Rac and Cdc42 is the serine/threonine kinase Pak (p65pak). We show here that expression of a catalytically inactive mutant Pak, Pak1(R299), inhibits Ras transformation of Rat-1 fibroblasts but not of NIH 3T3 cells. Typically, 90 to 95% fewer transformed colonies were observed in cotransfection assays with Rat-1 cells. Pak1(R299) did not inhibit transformation by the Raf oncogene, indicating that inhibition was specific for Ras. Furthermore, Rat-1 cell lines expressing Pak1(R299) were highly resistant to Ras transformation, while cells expressing wild-type Pak1 were efficiently transformed by Ras. Pak1(L83,L86,R299), a mutant that fails to bind either Rac or Cdc42, also inhibited Ras transformation. Rac and Ras activation of JNK was inhibited by Pak1(R299) but not by Pak1(L83,L86,R299). Ras activation of ERK was inhibited by both Pak1(R299) and Pak1(L83,L86,R299), while neither mutant inhibited Raf activation of ERK. These results suggest that Pak1 interacts with components essential for Ras transformation and that inhibition can be uncoupled from JNK but not ERK signaling.

Animals↗
PubMed1996

Improved islet isolation from rat pancreas using 35% bovine serum albumin in combination with Dextran gradient separation.

We have developed a gradient separation technique in which albumin-coated (35% BSA) rat islets are isolated in Dextran (BSA/D). Versus Dextran alone (DA), BSA/D increases mean islet yield from 850 +/- 115 to 1222 +/- 210 islets/donor (mean +/- SD, P=.001). With numbers of donors held constant, the time to euglycemia was significantly shorter in syngenic recipients of BSA/D than DA islets (5.7 +/- 4.8 versus 14.2 +/- 5.6 days, P=.02). However, when the number of islets were held constant, differences in time to cure were not statistically significantly different (P>.19): with 1200 islets, 3.8 +/- 2.8 (DSA/D) versus 9.2 +/- 8.2 (DA) days; with 750 islets, 18.3 +/- 5.8 (BSA/D) versus 18.0 +/- 4.5 (DA) days. In all groups, posttransplant day 1 glucose was lowest with the BSA/D technique. Thus BSA/D isolation gives a higher yield with at least equal viability. We recommend the BSA/D technique for its efficiency and economy.

Animals↗
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

Long-term outcome and cost-effectiveness of parenteral nutrition for acute gastrointestinal failure.

Although there are several published audits of long-term home parenteral nutrition for chronic gastrointestinal failure, there is little data concerning the long-term outcome following prolonged in-patient parenteral nutrition for an episode of acute gastrointestinal failure. Between 1983 and 1 July 1993, 162 patients received total parenteral nutrition (TPN) in our unit for acute gastrointestinal failure for a total of 4997 patient days and using 192 central venous catheters. Over the 10 years there were 11 mechanical complications resulting in one death. Although the overall catheter infection rate was 5.7%, in the last 4 years it was 0%, associated with a reduction in the frequency of site dressing and change of giving set from three times to once weekly. All patients had lost more than 10% of their body weight before TPN. In the non-malignant group, fed for more than 21 days (mean 50 days), the 10-year survival was 74% at a cost of 4723 pounds sterling per year of life saved. In the malignant group, the 5-year survival was 27% at a cost of 8351 pounds sterling per year of life saved. These costs compare favourably with other technologies, such as dialysis for acute renal failure. Better patient selection, fewer complications and lower costs are obtained when this treatment is carried out by an expert team.

Journal Article↗
PubMed1996

Total wrist fusion. A functional assessment.

Twenty cases of total wrist fusion, performed for post-traumatic conditions, were reviewed objectively, subjectively and radiologically. All patients were satisfied with the position of the fused wrist and had good pain relief. All patients would have had the procedure sooner, having had an average of three operations on the wrist before the fusion. There was a high complication rate (45%), although only four patients required further procedures for those complications. Hand function, as assessed by the Jebsen and Purdue tests, was found to be poor; this may be due to a reduced range of finger movements. There was no correlation between position of fusion, carpal height or number of joints radiologically fused, and the pain score, grip strength or Buck-Gramcko score.

Adult↗
PubMed1996

Geographic variation in sexual behaviour in Britain: implications for sexually transmitted disease epidemiology and sexual health promotion.

OBJECTIVES: To explore geographical variation in sexual behaviour in Great Britain with reference to the prevalence of HIV infection. DESIGN: The National Survey of Sexual Attitudes and Lifestyles comprises a randomly selected, representative sample of almost 19,000 men and women aged 16-59 years living in Great Britain. METHODS: The survey was carried out using a combination of face-to-face interview and self-completion questionnaires and a wide range of data was collected. In this study, data on numbers and sex of sexual partners, condom use, injecting drug use, perception of risk of AIDS and lifestyle change were analysed, and comparisons were made between the different geographical areas in Great Britain. RESULTS: In the last 5 years, men living in Inner London were more likely to have a male partner [odds ratio (OR), 5.6; 95% confidence interval (CI), 3.1-10.0] or to have had 10 or more female partners (OR, 2.4; 95% CI, 1.6-3.6) than men living in other parts of the country. Similar results were observed for women living in Inner London: OR for a female partner in the last 5 years was 4.1 (95% CI, 1.6-10.2) and for five or more male partners in the last 5 years was 2.1 (95% CI, 1.5-2.8). More complex, but less striking patterns of behaviour were seen in different parts of the country. Both men and women living in Inner London were more likely to recognize that they were at some risk of acquiring HIV and were also more likely to report a change in sexual lifestyle. CONCLUSIONS: These analyses highlight the difficulties inherent in extrapolating from sexual behaviour data gathered using purposive samples to the population as a whole. The results are consistent with the known epidemiology of HIV and sexually transmitted diseases in Britain. The data suggest that cases of HIV will continue to be concentrated in Inner London, but Londoners are particularly aware of their risk. Reported behaviour change in response to perception of risk of AIDS underlines the importance of effective health promotion.

Adolescent↗
PubMed1996

Halothane-induced liver injury in guinea-pigs: importance of cytochrome P450 enzyme activity and hepatic blood flow.

The basis for susceptibility to halothane-induced liver necrosis in guinea-pigs was examined. In hepatic microsomes, the following were similar in susceptible and resistant animals: total cytochrome (CYP) P450 (P450), phenobarbital-inducible pathways of mixed function oxidation (androstenedione 6 beta- and 16 beta-hydroxylase activities) and the CyP2E1-catalysed pathway of N-nitrosodimethylamine N-demethylase activity. Similarly, immunohistochemical staining of CYP2E1 protein was equivalent in livers from susceptible and resistant guinea-pigs. Prior treatment with the P450-inhibitors, metyrapone and SKF-525A ameliorated halothane-induced liver damage in susceptible animals. Conversely, in resistant guinea-pigs, stimulation of hepatic CYP2E1 activity by treatment with 4-methylpyrazole produced severe hepatotoxicity after re-exposure to halothane. These results confirm the conclusions of others, that P450-mediated metabolism produces halothane-induced liver necrosis in the guinea-pig model but, as in other work, the data fail to explain why no difference in activity of these enzymes could be found between susceptible and resistant guinea-pigs. To establish whether a differential effect on hepatic blood flow between susceptible and resistant guinea-pigs could explain this paradox, studies were performed using a radiolabelled microsphere technique. The effect of halothane on lowering cardiac output was identical in both groups of animals and halothane significantly reduced hepatic arterial but not portal blood flow. The effect on arterial blood flow was more profound in susceptible guinea-pigs (0.67 +/- 0.17% of injected microspheres) than in resistant animals (0.99 +/- 0.13%; P < 0.005). It is concluded that P450-catalysed metabolism and reduced hepatic blood flow are both necessary to produce halothane-induced liver injury in susceptible guinea-pigs, but it is the effect of halothane on hepatic arterial blood flow that differs between susceptible and resistant animals.

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↗
PubMed1996

Who goes to sexually transmitted disease clinics? Results from a national population survey.

OBJECTIVES: To examine the pattern of attendance at sexually transmitted disease (STD) clinics in Britain. To compare the demographic characteristics, behaviours and attitudes of STD clinic attenders with those of non-attenders, and to assess the extent to which STD clinics are used by those with high-risk sexual lifestyles. DESIGN: Random sample general population survey of sexual attitudes and lifestyle. SUBJECTS: 18,876 randomly selected men and women resident in Britain aged 16-59 years. MAIN OUTCOME MEASURES: Demographic characteristics, pattern of homosexual partnerships, heterosexual partnerships, payment for sex, abortion, drug injection in the last five years, and attitudes to sexual behaviours amongst 512 respondents who had attended STD clinic in the last five years compared with those who had not. RESULTS: 8.3% of men and 5.6% of women had attended a clinic in their lifetime and 3.4% and 2.6% respectively in the last five years. Attendance rates varied substantially with area of residence. 11% of Inner London residents had attended in the last five years. In multivariate analysis, STD clinic attendance for men was most strongly associated with increased numbers of heterosexual partners, (OR = 6.01 (4.44-8.15) and homosexual partnerships (OR = 9.59 (5.83-15.8)) and more weakly associated with payment for sex, non-manual social class, age 25-44, unmarried status and smoking. Clinic attendance for women was most strongly associated with numbers of heterosexual partners (OR = 3.74 (2.76-5.08) and injecting drug use (OR = 4.39 (1.73-11.1)). A weaker independent association was found with a history of abortion, anal sex, non-manual social class, non-married status and age 16-24. From the total population, 1 in 6 men and 1 in 7 women in the top 5% of the distribution for numbers of heterosexual partners and 1 in 5 men paying for sex and 1 in 4 of those with a homosexual partner had attended a clinic in the last five years. The probability of attendance increased with multiple risk behaviours. Of women 64.2% and of men 69.7% attending clinics reported major risk markers for STD transmission. CONCLUSIONS: STD clinics in Britain are used by a wide demographic spectrum of the population. The behaviours, but not the attitudes, of attenders differed markedly from those of non-attenders. Clinics are relatively efficient in attracting only those with high-risk lifestyles, but, at a population level, the minority of those reporting risk-markers for STD transmission attend clinics. These findings suggest that STD clinics are an important focus for sexual health promotion, but that community programmes are also important for reaching non-attenders.

Adolescent↗
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↗