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Biomedical subjects

J Wells

Publications and source records attributed to J Wells.

At least 37 records · Page 2Linked to original sources
PubMed2001

Mre11 complex and DNA replication: linkage to E2F and sites of DNA synthesis.

We show that the Mre11 complex associates with E2F family members via the Nbs1 N terminus. This association and Nbs1 phosphorylation are correlated with S-phase checkpoint proficiency, whereas neither is sufficient individually for checkpoint activation. The Nbs1 E2F interaction occurred near the Epstein-Barr virus origin of replication as well as near a chromosomal replication origin in the c-myc promoter region and was restricted to S-phase cells. The Mre11 complex colocalized with PCNA at replication forks throughout S phase, both prior to and coincident with the appearance of nascent DNA. These data suggest that the Mre11 complex suppresses genomic instability through its influence on both the regulation and progression of DNA replication.

Animals↗
PubMed2000

The protective effects of hypoxia-induced hypometabolism in the Nautilus.

Specimens of Nautilus pompilius were trapped at depths of 225-300 m off the sunken barrier reef southeast of Port Moresby, Papua New Guinea. Animals transported to the Motupore Island laboratory were acclimated to normal habitat temperatures of 18 degrees C and then cannulated for arterial and venous blood sampling. When animals were forced to undergo a period of progressive hypoxia eventually to encounter ambient partial pressure of oxygen (PO2) levels of approximately 10 mmHg (and corresponding arterial PO2's of approximately 5 mmHg), they responded by lowering their aerobic metabolic rates to 5-10% of those seen in resting normoxic animals. Coincident with this profound metabolic suppression was an overall decrease in activity, with brief periods of jet propulsion punctuating long periods of rest. Below ambient PO2 levels of 30-40 mmHg, ventilatory movements became highly periodic and at the lowest PO2 levels encountered, ventilation occasionally ceased altogether. Cardiac output estimated by the Fick equation decreased during progressive hypoxia by as much as 75 80%, and in the deepest hypometabolic states heart rates slowed to one to two cycles of very low amplitude per minute. By the end of 500 min exposure to ambient PO2 levels of 10 mmHg or less, the anaerobic end products octopine and succinate had increased significantly in adductor muscle and heart, respectively. Increased concentrations of octopine in adductor muscle apparently contributed to a small intracellular acidosis and to the development of a combined respiratory and metabolic acidosis in the extracellular compartment. On the other hand, increases in succinate in heart muscle occurred in the absence of any change in cardiac pHi. Taken together, we estimate that these anaerobic end products would make up less than 2% of the energy deficit arising from the decrease in aerobic metabolism. Thus, metabolic suppression is combined with a massive downregulation of systemic O2 delivery to match metabolic supply to demand.

Acid-Base Equilibrium↗
PubMed2000

Development and evaluation of an interactive CD-ROM refusal skills program to prevent youth substance use: "refuse to use".

An interactive CD-ROM program designed to reduce adolescent substance use was developed and evaluated. The program uses video vignettes to teach refusal skills and socially acceptable responses to substance use situations, specifically offers of marijuana. In a randomized pretest-to-posttest experiment with 74 public school students from six classes in three high schools, significant changes were observed at posttest on (1) the adolescent's personal efficacy to refuse the offer of marijuana, (2) the adolescent's intention to refuse marijuana if offered, and (3) the adolescent's perceptions of the social norms associated with substance use and the importance of respecting another's decision to refuse a drug offer. In addition, adolescents in the treatment condition were able to recall approximately 50% of the portrayed refusal strategies. Findings are discussed with regard to the potential benefits of an interactive multimedia approach for conducting substance use interventions.

Adolescent↗
PubMed2000

A heterogeneous outbreak of Enterobacter cloacae and Serratia marcescens infections in a surgical intensive care unit.

OBJECTIVE: To investigate an outbreak of invasive disease due to Enterobacter cloacae and Serratia marcescens in a surgical intensive care unit (ICU). DESIGN: Pulsed-field gel electrophoresis (PFGE) analysis of restriction fragments was used to characterize the outbreak isolate genotypes. A retrospective cohort study of surgical ICU patients was conducted to identify risk factors associated with invasive disease. Unit staffing data were analyzed to compare staffing levels during the outbreak to those prior to and following the outbreak. SETTING: An urban hospital in San Francisco, California. PATIENTS: During the outbreak period, December 1997 through January 1998, there were 52 patients with a minimum ICU stay of > or = 72 hours. Of these, 10 patients fit our case definition of recovery of E. cloacae or S. marcescens from a sterile site. RESULTS: PFGE analysis revealed a highly heterogeneous population of isolates. Bivariate analysis of patient-related risk factors revealed duration of central lines, respiratory colonization, being a burn patient, and the use of gentamicin or nafcillin to be significantly associated with invasive disease. Both respiratory colonization and duration of central lines remained statistically significant in a multivariate analysis. Staffing data suggested a temporal correlation between understaffing and the outbreak period. CONCLUSIONS: Molecular epidemiological techniques provided a rapid means of ruling out a point source or significant cross-contamination as modes of transmission. In this setting, patient-related risk factors, such as respiratory colonization and duration of central lines, may provide a focus for heightened surveillance, infection control measures, and empirical therapy during outbreaks caused by common nosocomial pathogens. In addition, understaffing of nurses may have played a role in this outbreak, highlighting the importance of monitoring staffing levels.

Cohort Studies↗
PubMed2000

Target gene specificity of E2F and pocket protein family members in living cells.

E2F-mediated transcription is thought to involve binding of an E2F-pocket protein complex to promoters in the G(0) phase of the cell cycle and release of the pocket protein in late G(1), followed by release of E2F in S phase. We have tested this model by monitoring protein-DNA interactions in living cells using a formaldehyde cross-linking and immunoprecipitation assay. We find that E2F target genes are bound by distinct E2F-pocket protein complexes which change as cells progress through the cell cycle. We also find that certain E2F target gene promoters are bound by pocket proteins when such promoters are transcriptionally active. Our data indicate that the current model applies only to certain E2F target genes and suggest that Rb family members may regulate transcription in both G(0) and S phases. Finally, we find that a given promoter can be bound by one of several different E2F-pocket protein complexes at a given time in the cell cycle, suggesting that cell cycle-regulated transcription is a stochastic, not a predetermined, process.

3T3 Cells↗
PubMed2000

Randomised trial of iodine intake and thyroid status in preterm infants.

BACKGROUND: Low levels of circulating thyroid hormones have been associated with poorer general and neurodevelopmental outcome in preterm babies and it has been speculated that the association is causal. Low levels of circulating thyroid hormone have been reported after inadequate intake of iodine in preterm infants being fed milk formula. AIM: To investigate whether increased iodine intake from supplemented preterm formula would improve thyroid hormone levels in preterm babies (this study) and hence improve neurodevelopmental status (planned subsequent study). METHOD: A total of 121 preterm infants were entered into a randomised controlled trial of standard (68 microg/l) versus increased (272 microg/l) iodine in preterm formula. RESULTS: The two groups were comparable at recruitment. No evidence of an effect of the intervention on thyroid hormone levels was seen up to 41 weeks after conception. CONCLUSION: Calls for increased iodine content of preterm infant formulas are not justified by this study.

Female↗
PubMed2000

The long-term performance of DXA bone densitometers.

Long-term performance of a bone mass measuring device is an important criterion when considering the purchase of such equipment and has been regarded as an important feature of dual X-ray absorptiometry (DXA). The performance of a 6-year-old bone densitometer, the Lunar DPX alpha, which has undertaken 1500 scans annually over this period, was assessed. The short-term coefficient of variation calculated from 15 measurements with repositioning on a single day, using the Lunar aluminium phantom, was 0.242%. Long-term precision, also calculated by the coefficient of variation, was 0.548%. The manufacturer's quality control (QC) procedure was performed daily and allowed the machine to be used except on 15 occasions when bone density measurements could be acquired after rebooting. However, a 2.2% shift in phantom values occurred in July 1996 owing to a photomultiplier tube failure, but this did not produce a failure in the Lunar QC. The optical disc drive was replaced in July 1997. The machine failed to back up on six occasions over the last 2 years owing to software corruption and the acquired femur data were not saved on seven occasions owing to overloading of the memory buffer. In conclusion, expected hardware failure and minor software problems have occurred. We were concerned that the manufacturer's QC failed to detect a 2% shift in the phantom bone mineral density values and recommend regular measurements of the Lunar aluminum phantom in addition to the daily QC measurement of the tissue-equivalent block. We were nevertheless impressed by the long-term stability and reproducibility of the Lunar DPX alpha.

Absorptiometry, Photon↗
PubMed2000

Stop fake beer.

Explore the source record for details and available documents.

Adolescent↗
PubMed1999

PC12 cells transfected with a C-terminal fragment of the amyloid precursor protein (APP C-100), exhibit enhanced sensitivity to the calcium ionophore A23187, and diminished sensitivity to hydrogen peroxide.

Extracellular neuritic plaques are a hallmark of Alzheimer's disease. The core protein of plaques is Abeta, a 39-43 amino acid peptide derived from the amyloid precursor protein (APP). APP C-100 is a C-terminal fragment of APP, 100 amino acids long, whose sequence includes Abeta. To determine whether APP C-100 expression alters cellular vulnerability to calcium and H(2)O(2), rat PC12 cells were modified to overexpress APP C-100. Cellular survival (as measured in the MTT assay) was determined as a function of concentration for the calcium ionophore, A23187, and for H(2)O(2) in APP C-100 transfectants and vector-transfected controls. APP C-100 expression significantly increased cellular vulnerability to A23187, and decreased vulnerability to H(2)O(2).

Amyloid beta-Protein Precursor↗
PubMed1999

Older drivers and cataract: driving habits and crash risk.

BACKGROUND: Cataract is a leading cause of vision impairment in older adults, affecting almost half of those over age 75 years. Driving is a highly visual task and, as with other age groups, older adults rely on the personal automobile for travel. The purpose of this study was to examine the role of cataract in driving. METHODS: Older adults (aged 55-85 years) with cataract (n = 279) and those without cataract (n = 105) who were legally licensed to drive were recruited from eye clinics to participate in a driving habits interview to assess driving status, exposure, difficulty, and "space" (the distance of driving excursions from home base). Crash data over the prior 5 years were procured from state records. Visual functional tests documented the severity of vision impairment. RESULTS: Compared to those without cataract, older drivers with cataract were approximately two times more likely to report reductions in days driven and number of destinations per week, driving slower than the general traffic flow, and preferring someone else to drive. Those with cataract were five times more likely to have received advice about limiting their driving. Those with cataract were four times more likely to report difficulty with challenging driving situations, and those reporting driving difficulty were two times more likely to reduce their driving exposure. Drivers with cataract were 2.5 times more likely to have a history of at-fault crash involvement in the prior 5 years (adjusted for miles driven/week and days driven/week). These associations remained even after adjustments for the confounding effects of advanced age, impaired general health, mental status deficit, or depression. CONCLUSIONS: Older drivers with cataract experience a restriction in their driving mobility and a decrease in their safety on the road. These findings serve as a baseline for our ongoing study evaluating whether improvements in vision following cataract surgery expand driving mobility and improve driver safety.

Accidents, Traffic↗
PubMed1999

Sampling procedures and survey methodologies for the 1996 survey with comparisons to earlier national roadside surveys.

This article describes the multistage sampling system employed in the 1996 national roadside survey and compares it to the sampling methods employed in the two prior surveys in 1973 and 1986. Also described are the data collection procedures at the selected sites, the breath-test devices used to collect blood alcohol concentration (BAC) data, and the methods used to impute BAC values where breath-test measures were not obtained. Overall, almost twice as many (6,298 in 1996 compared to 3,698 in 1973 and 3,043 in 1986) drivers were interviewed in the most recent national survey as in the previous efforts. The procedures implemented in the three surveys are sufficiently similar to permit comparison of these surveys conducted at 10-year intervals.

Alcohol Drinking↗
PubMed1999

Antegrade continence enema for the treatment of fecal incontinence in adults: use of gastric tube for catheterizable access to the descending colon.

PURPOSE: We describe the use of a gastric segment in performing the antegrade continence enema procedure in patients with refractory fecal incontinence. MATERIALS AND METHODS: The antegrade continence enema procedure was performed in 4 women and 3 men with refractory neurogenic fecal incontinence. Preoperative evaluation included defecography and anorectal manometry. Operative technique involves tunneling a 10 cm. segment of tubularized stomach isolated along the greater curve with preservation of the right gastroepiploic vessels through the anterior tenia of the colon just distal to the splenic flexure. After the stoma is mature the patient passes a catheter and runs 1 to 2 l. warm tap water through it while seated on the toilet. Digital stimulation may be required to initiate bowel emptying and irrigation is continued until clear. RESULTS: Creation of a nonrefluxing catheterizable gastric tube to the descending colon was successful in all 7 patients. At a mean postoperative followup of 22.4 months all patients are continent and use antegrade continence enema irrigation every other day on average. One patient required early revision because of stomal stenosis. Special measures include application of a generic antacid tablet to the stoma and use of a skin barrier. CONCLUSIONS: Catheterizable access to the descending colon for the antegrade continence enema procedure more closely approximates normal defecation patterns by emptying ("unloading") the left side of the colon. The stomach is a suitable option in close proximity for this purpose and is especially advantageous when the appendix is not available. The antegrade continence enema procedure using a gastric segment can be safely and effectively performed, and is well suited for use by reconstructive surgeons who are familiar with the Mitrofanoff principle.

Adult↗
PubMed1998

c-Myc target gene specificity is determined by a post-DNAbinding mechanism.

Uncertainty as to which member of a family of DNA-binding transcription factors regulates a specific promoter in intact cells is a problem common to many investigators. Determining target gene specificity requires both an analysis of protein binding to the endogenous promoter as well as a characterization of the functional consequences of transcription factor binding. By using a formaldehyde crosslinking procedure and Gal4 fusion proteins, we have analyzed the timing and functional consequences of binding of Myc and upstream stimulatory factor (USF)1 to endogenous cellular genes. We demonstrate that the endogenous cad promoter can be immunoprecipitated with antibodies against Myc and USF1. We further demonstrate that although both Myc and USF1 can bind to cad, the cad promoter can respond only to the Myc transactivation domain. We also show that the amount of Myc bound to the cad promoter fluctuates in a growth-dependent manner. Thus, our data analyzing both DNA binding and promoter activity in intact cells suggest that cad is a Myc target gene. In addition, we show that Myc binding can occur at many sites in vivo but that the position of the binding site determines the functional consequences of this binding. Our data indicate that a post-DNA-binding mechanism determines Myc target gene specificity. Importantly, we have demonstrated the feasibility of analyzing the binding of site-specific transcription factors in vivo to single copy mammalian genes.

3T3 Cells↗
PubMed1998

Drinking and driving in the United States: the 1996 National Roadside Survey.

Following the same general principles of its two predecessors in 1973 and 1986, the 1996 National Roadside Survey of weekend, nighttime drivers in the 48 contiguous states interviewed and breath tested over 6000 noncommercial four-wheel vehicle operators between September 6 and November 9, 1996. Results indicated that the total number of drinking drivers fell by about one-third between 1986 and 1996; however, there was no significant change in the number of drivers at blood alcohol concentrations (BACs) at or above 0.05. Compared to 1973, the proportion of women drivers on the roads during weekend nights has increased significantly. Moreover, relative to males, the proportion of female drivers who have been drinking has increased over the last decade. The number of drivers under the age of 21 with a BAC at or above 0.10 decreased significantly from 1986 to 1996.

Adult↗
PubMed1998

Randomised controlled trial of biofeedback training in persistent encopresis with anismus.

BACKGROUND: Paradoxical external anal sphincter contraction during attempted defecation (anismus) is thought to be an important contributor to chronic faecal retention and encopresis in children. Biofeedback training can be used to teach children to abolish this abnormal contraction. METHODS: A randomised controlled trial in medical treatment resistant and/or treatment dependent children with anismus using surface electromyographic (EMG) biofeedback training to determine whether such training produces sustained faecal continence. Up to four sessions of biofeedback training were conducted at weekly intervals for each patient. Anorectal manometry was performed before randomisation and six months later. Parents of patients completed the "child behaviour checklist" (CBCL) before randomisation and at follow up. RESULTS: Sixty eight children underwent anorectal manometry and EMG. Of these, 29 had anismus (ages 4-14 years) and were randomised to either EMG biofeedback training and conventional medical treatment (BFT) (n = 14) or to conventional medical treatment alone (n = 15). All but one child were able to learn relaxation of the external anal sphincter on attempted defecation. At six months' follow up, laxative free remission had been sustained in two of 14 patients in the BFT group and in two of 15 controls (95% confidence interval (CI) on difference, -24% to 26%). Remission or improvement occurred in four of 14 patients in the BFT group and six of 15 controls (95% CI on difference, -46% to 23%). Of subjects available for repeat anorectal manometry and EMG at six months, six of 13 in the BFT group still demonstrated anismus v 11 of 13 controls (95% CI on difference, -75% to -1%). Of the four patients in full remission at six months, only one (in the BFT group) did not exhibit anismus. Rectal hyposensitivity was not associated with remission or improvement in either of the groups. Mean CBCL total behaviour problem scores were not significantly different between the BFT and control groups, but there was a significant improvement in CBCL school scale scores in the BFT group, and this improvement was significantly greater than that seen in the control group. CONCLUSIONS: The result of this study, together with those reported in other controlled trials, argues against using biofeedback training in children with encopresis.

Adolescent↗