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Biomedical subjects

J Stevens

Publications and source records attributed to J Stevens.

At least 55 records · Page 3Linked to original sources

Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein.

The adenomatous polyposis coli (APC) tumor-suppressor protein, together with Axin and GSK3beta, forms a Wnt-regulated signaling complex that mediates phosphorylation-dependent degradation of beta-catenin by the proteasome. Siah-1, the human homolog of Drosophila seven in absentia, is a p53-inducible mediator of cell cycle arrest, tumor suppression, and apoptosis. We have now found that Siah-1 interacts with the carboxyl terminus of APC and promotes degradation of beta-catenin in mammalian cells. The ability of Siah-1 to downregulate beta-catenin signaling was also demonstrated by hypodorsalization of Xenopus embryos. Unexpectedly, degradation of beta-catenin by Siah-1 was independent of GSK3beta-mediated phosphorylation and did not require the F box protein beta-TrCP. These results indicate that APC and Siah-1 mediate a novel beta-catenin degradation pathway linking p53 activation to cell cycle control.

Adenomatous Polyposis Coli Protein↗

Evolutionary rate differences in trypanosomes.

Ribosomal RNA-based studies of trypanosome phylogenies have highlighted considerable differences in genetic diversity within clades in the genus Trypanosoma and several-fold substitution rate differences between clades have been identified. While early 18S rRNA-based studies were hampered by highly variable substitution rates and long-branch attraction, it is apparent that genuine differences in evolution rates within localized clades do exist and questions remain regarding what rate or rates such clades are evolving at and why is the application of a single clock to trypanosome evolution so inappropriate? In this study, we explore rate heterogeneity in the commonly used 18S rRNA gene across genus Trypanosoma, using a maximum likelihood (ML) approach to explore local rate variations in clades of biological interest.

Animals↗

Automatic atrial anti-tachy pacing for the termination of spontaneous atrial tachyarrhythmias: clinical experience with a novel dual-chamber pacemaker.

UNLABELLED: Automatic atrial anti-tachy pacing (aATP) is a novel approach to treat paroxysmal/persistent atrial tachyarrhythmias in pacemaker patients. To evaluate the efficacy of aATP in terminating spontaneous atrial flutter/tachycardia episodes (AT), a dual-chamber stimulator with extensive diagnostic capabilities and programmable aATP therapies (AT500(TM), Medtronic Inc.) was implanted in 30 patients with conventional pacing indications. During a mean follow-up time of 5.5 (1-12) months, aATP was delivered for 10494 AT. According to automatic device analysis, 8289 AT were treated with success (success-rate 79.0%). On 468 AT stored with the corresponding atrial EGM, an additional manual analysis was performed. The success-rate based on automatic analysis of these AT episodes (73.1%) was comparable to that found for all treated AT (79.0%), but manual EGM analysis revealed that only 209 of the 468 treated AT episodes (44.7%) were actually terminated by aATP. The aATP success-rate in the slower (cycle length 360-270 ms) AT detection zone was significantly higher (73.8%, 62/84 eps) than in the overlapping, faster (cycle length 270-220 ms) AT zone (38.3%, 147/384 eps, P<0.01). CONCLUSIONS: According to manual analysis, 1. aATP was safe and had a success-rate of 44.7%, 2. aATP success-rate was higher for AT in the slower than in the faster detection zone and 3. automatic analysis overestimated the efficacy of aATP.

Adult↗

Weight loss attempts and attitudes toward body size, eating, and physical activity in American Indian children: relationship to weight status and gender.

OBJECTIVE: This study examined dieting, weight perceptions, and self-efficacy to eat healthy foods and engage in physical activity and their relationships to weight status and gender among American Indian elementary schoolchildren. RESEARCH METHODS AND PROCEDURES: Data for this study were collected as part of the baseline examination for the Pathways study. Participants were 1441 second- through third-grade American Indian children in 41 schools representing seven tribes in Arizona, New Mexico, and South Dakota who filled out a questionnaire and had heights and weights taken. RESULTS: Forty-two percent of the children were overweight or obese. No differences were found between overweight/obese and normal weight children for healthy food intentions or self-efficacy. Heavier children (especially those with body mass index > 95th percentile) were more likely to have tried to lose weight or were currently trying to lose weight. No gender differences were found. Normal weight children chose a slightly heavier body size as most healthy compared with overweight/obese children. DISCUSSION: The results indicate that children are concerned about their weight and that weight modification efforts are common among overweight American Indian children. School, community, and family-based programs are needed to help young people adopt lifelong healthful eating and physical activity practices.

Arizona↗

Sensitivity and specificity of anthropometrics for the prediction of diabetes in a biracial cohort.

OBJECTIVE: To evaluate the ability of body mass index, waist circumference, waist-to-hip ratio, and combinations of these variables to discriminate individuals who will develop diabetes in adulthood. RESEARCH METHODS AND PROCEDURES: Data were from 45- to 64-year-old men and women who were members of the Atherosclerosis Risk in Communities cohort. The analysis sample consisted of 12,814 African American and white participants who were free of diabetes at baseline. Body mass index, waist circumference, waist-to-hip ratio, and diabetes incidence (defined as one glucose measure > or =126 mg/dL after fasting for at least 8 hours, one nonfasting glucose measure > or =200 mg/dL, and self-report of diabetes or report of taking medication for diabetes). RESULTS: 1515 new cases of diabetes were identified over the 9-year follow-up. Areas under receiver operating characteristic curves ranged from 0.66 to 0.73 for single measures. The curves were smooth, with no indication of a threshold. Waist tended to have the highest receiver operating characteristic statistic in all groups, but differences were small. DISCUSSION: The three anthropometric indices tested were approximately equivalent in their ability to predict diabetes. Sensitivity and specificities differed among ethnic and gender groups.

Anthropometry↗

The influence of intraperitoneal bupivacaine on pain following major laparoscopic gynaecological procedures.

We present the results of a randomised, double-blind controlled trial to determine the effect of adding bupivacaine to intraperitoneal Hartmann's solution, used to reduce the incidence of postoperative adhesions, on postoperative pain and on analgesic consumption in patients presenting for major laparoscopic gynaecological procedures. Fifty-six women were studied and postoperative analgesic requirements and visual analogue scores were used to assess the pain experienced by the treatment group when compared with the control group. There was no statistical difference in the pain scores between the two groups at any time during the study period (Student's t-test; p = 0.29-0.74) nor was there any difference in analgesic consumption (Mann-Whitney U-test; p = 0.34-0.79).

Adult↗

State of the art neonatal hearing screening with auditory brainstem response.

The purpose of this paper is to briefly review some of the aspects of the auditory brainstem response (ABR) that are important in its use as a method of screening and assessing hearing in the neonate. The paper starts by considering the technical limitations of click ABR and explores the alternative electrophysiological methods. It then considers where ABR is required in the screening of neonates. The role of bone conduction ABR in estimating the conductive component of any hearing loss is discussed. Finally, the ability of the neonatal ABR to predict the long-term audiometric outcome of permanently hearing-impaired children is considered.

Evoked Potentials, Auditory, Brain Stem↗

Performance of neonatal and infant hearing screens: sensitivity and specificity.

The terms 'sensitivity' and 'specificity' are defined and some of the factors that determine their values are discussed in the context of screening for permanent childhood hearing loss. There is a need to distinguish between the values observed in 'simple experiments' and those that may be obtained under more realistic 'field' conditions. It is not feasible to give a meta-analytic overview of published data because of the variety of methods and objectives used in those studies published in the literature. However, a qualitative synthesis of the data is possible. This suggests that most proposed neonatal hearing screening tests, when implemented in accordance with a programme of quality assurance, can be reasonably accurate at a modest cost. However, the optimal combination of tests and test parameters for given populations has not yet been fully researched. The infant distraction test screen has a lower sensitivity than neonatal hearing screening tests, particularly for moderate impairments, accompanied by a fairly low specificity.

Child Health Services↗

Patterns of long-term change in body composition are associated with diet, activity, income and urban residence among older adults in China.

Studies describing patterns of long-term change in body composition are lacking. Using longitudinal data on 608 healthy, nonobese Chinese (aged 50-70 y) from the 1993 and 1997 China Health and Nutrition Surveys, this article describes the prevalence, sociodemographic and lifestyle correlates of patterns of long-term change in midarm muscle area (MAMA) and body fat (waist circumference). All patterns of change (loss, maintenance [Delta < 1.3 cm(2)], or gain of MAMA with concurrent loss, maintenance [Delta < 2 cm(2)] or gain of body fat), were observed for this sample. After controlling for sex, baseline age, urban residence, height, weight, income, MAMA, waist circumference, smoking status, activity level, mean daily energy and protein intakes (from three 24-h recalls), and change in height, it was determined that subjects who lost both arm muscle and body fat were distinguished from subjects who lost arm muscle but gained body fat by lower income and energy intake at baseline. Although protein intakes at baseline did not differ between the groups that lost arm muscle, protein intakes were significantly higher for subjects who gained both muscle and fat. Patterns of change involving gains in arm muscle were associated with increased protein intake, urban residence, as well as moderate or heavy levels of physical activity at baseline. Variation in protein intake, physical activity, and urban residence also differentiated between the groups that gained fat. Patterns of age-related change in body composition appear associated with modifiable variables, including income, urban residence, activity and protein and energy intake.

Aged↗

The use of electrical stimulation to increase quadriceps femoris muscle force in an elderly patient following a total knee arthroplasty.

BACKGROUND AND PURPOSE: Persistent residual quadriceps femoris muscle force deficits after total knee arthroplasty (TKA) are commonly reported and can prevent patients from returning quickly and fully to functional activities. Neuromuscular electrical stimulation offers a potentially more effective means of increasing muscle force than current rehabilitation protocols. CASE DESCRIPTION: The patient was a 66-year-old man. Neuromuscular electrical stimulation for increasing quadriceps femoris muscle force was initiated 3 weeks after TKA for 11 sessions to supplement stretching exercises and a high-intensity volitional strengthening program. OUTCOME: The patient's isometric quadriceps femoris muscle force increased from 50% (involved/uninvolved) at 3 weeks after surgery to 86% at 8 weeks after surgery. A concurrent increase in his uninvolved quadriceps femoris muscle force concealed the patient's true increase in his involved quadriceps femoris muscle force in a side-to-side comparison. The patient's final involved quadriceps femoris muscle force (10 weeks after surgery) was 93% of the initial uninvolved quadriceps femoris muscle force. DISCUSSION: Our patient was able to return to independent activities of daily living and recreational activities, with force gains that surpassed those reported in the literature.

Aged↗

Arterial distensibility and physical activity in the ARIC study.

PURPOSE: Arterial distensibility decreases with age. This decrease may be associated with the initiation and/or progression of hypertension and atherosclerosis and may be attenuated by positive lifestyle habits, including habitual physical activity. We tested the hypothesis that self-reported sport, leisure, and work physical activity is associated with greater arterial distensibility (i.e., carotid artery pulsatile diameter changes). METHODS: The Atherosclerosis Risk in Communities (ARIC) study assessed left common carotid arterial diameters and intimal-medial wall thickness (IMT) using B-mode ultrasound techniques, in 10,644 African-American and white men and women aged 45-64 yr and free of cardiovascular disease. RESULTS: Work activity, but not sports or leisure activity, was weakly associated with greater arterial distensibility in an ANCOVA model adjusted for blood pressure and other covariates (diastolic arterial diameter, pulse pressure, pulse pressure squared, age, race, sex, smoking, dietary fat intake, height, education, and clinical center) (P for linear trend = 0.03). Vigorous sports activity was weakly positively associated with arterial distensibility (arterial diameter change (mean +/- SE in mm) 0.42 +/- 0.004 vs 0.41 +/- 0.002 for the 12.7% of participants reporting any vs no vigorous activity, P = 0.02), and this association was not attenuated by adjustment for IMT, body mass index, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or diabetes. Repeated analyses with traditional arterial stiffness indices showed similar findings for vigorous but not work activity. CONCLUSION: In contrast to several smaller studies, these findings do not support the hypothesis that habitual physical activity has a strong, consistent positive effect on arterial distensibility.

Arteries↗

Bleomycin upregulates gene expression of angiotensin-converting enzyme via mitogen-activated protein kinase and early growth response 1 transcription factor.

Pulmonary fibrosis is a progressive disorder characterized by the loss of alveolar architecture through epithelial and endothelial cell apoptosis and fibroblast proliferation. Recent studies showed that angiotensin-converting enzyme (ACE) activity is increased in fibrotic tissues, and ACE inhibitors administered in vivo ameliorate fibrosis, suggesting that ACE may play a critical role. However, the regulation of ACE expression is not well understood. In the present study, we demonstrate that bleomycin, a chemotherapeutic agent which induces pulmonary fibrosis in animals and humans, increases gene expression of ACE. Treatment of primary bovine pulmonary artery endothelial cells with 0.1 to 1.0 microg/ml bleomycin increased ACE enzymatic activity and ACE mRNA, as monitored by hippuryl-L-histidyl-L-leucine assay and competitive quantitative reverse transcriptase polymerase chain reaction (RT-PCR), respectively. Luciferase reporter constructs showed that upregulation of ACE transcription by bleomycin is mediated through element(s) in the 97-bp ACE promoter. Bleomycin activated p42/p44 mitogen-activated protein kinase (MAPK) and induced nuclear translocation and activation of the early growth response (Egr)-1 transcription factor, a factor previously shown to positively regulate ACE expression. The MAPK kinase1/2 (MEK1/2) inhibitor U0126 blocked MAPK and Egr-1 activation by bleomycin, suggesting that Egr-1 activation is MAPK dependent. These data provide the first evidence that bleomycin activates ACE gene expression through the MAPK pathway and Egr-1.

Animals↗

The possible effects on health, comfort and safety of aircraft cabin environments.

A consultation was undertaken to investigate the views and concerns of stakeholders in the aircraft industry about the possible harmful effects on personal health, comfort and safety of aircraft cabin environments. Stakeholders were identified from a variety of sources including Government agencies, the Internet, House of Lords inquiry, and suggestions of interviewees. They represented: aircraft crews, aircraft constructors and engineers, government departments and authorities, holiday/flight companies, insurance companies, non-governmental organisations, occupational health physicians, passenger representatives, and independent researchers and consultants. Eighty-seven were contacted of which 57 were interviewed over the telephone using a semi-structured questionnaire. Their concerns were transcribed into a standard format and analysed qualitatively. Key stakeholders, along with Government officials, were invited to a workshop to discuss and prioritize the issues raised during the interviews. The main concerns expressed by the participants fell into five main areas: deep vein thrombosis, air quality, infection, cosmic radiation, and jet lag and work patterns. In addition, a number of safety concerns were raised as well as comments on the provision of appropriate advice to passengers. It was generally felt that further research was required on each of these subjects, as well as an improvement in the quality, quantity and availability of information provided for passengers prior to boarding a flight.

Air Pollution, Indoor↗

Clinical and radiological correlates of severity and surgery-related outcome in cervical spondylosis.

OBJECT: The aim of this study was to determine if radiological features could be used to predict outcome in patients with cervical spondylotic myelopathy (CSM). METHODS: The authors studied 69 patients consecutively referred to The National Hospital, Queen Square, for decompressive surgery. Data obtained from preoperative cervical spine magnetic resonance (MR) imaging studies were each analyzed on two separate occasions by two blinded radiologists. The parameters determined were signal change and the presence and severity of compression. Clinical outcome was determined by pre- and postoperative timed walks, as well as by evaluation of myelopathy disability index scores, Ranawat classification, and Nurick grades. There was good inter- and intraobserver reliability for determination of radiological data. A significant relationship was found between MR imaging signal change and surgery-related outcome, as reflected by improvement in walking parameters; however, this was confounded by the fact that signal change also related to preoperative walking parameters, and those patients for whom preoperative walking function was worse experienced greater functional improvement in walking postoperatively. The relationships between ambulatory-related data and severity or extent of spinal cord compression were less marked. CONCLUSIONS: Cervical cord compression and intrinsic MR imaging signal change correlate with clinical severity, and, in this population, the presence of signal change was correlated with better surgery-related outcome. However, confounding factors and the lack of strong correlation indicate that these radiological measurements are insufficient to be used as a reliable tool for predicting surgery-related benefits in individual patients.

Aged↗