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R J Lewis

Publications and source records attributed to R J Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2002

Expression of lux genes in a clinical isolate of Streptococcus pneumoniae: using bioluminescence to monitor gemifloxacin activity.

A clinical isolate of Streptococcus pneumoniae was transformed with a plasmid containing the lux operon of Photorhabdus luminescens that had been modified to function in gram-positive bacteria. Cells containing this plasmid produced light stably and constitutively, without compromising the growth rate. Light output was correlated with measurements of optical density and viable counts during exponential growth and provided a sensitive, real-time measure of the pharmacodynamics of the fluoroquinolone gemifloxacin.

Anti-Infective Agents↗
PubMed2002

Risk factors associated with non-fatal adolescent firearm injuries.

STUDY OBJECTIVES: To identify behavioral, environmental, and sociodemographic risk factors associated with non-fatal firearm injuries among inner city adolescents in the United States. DESIGN: A case-control study in which patients with firearm injury serve as cases and those with medical conditions serve as controls. SETTING: A level I trauma center in a metropolitan area serving a predominately lower socioeconomic status population. PARTICIPANTS: Cases were 45 consecutive patients 11-18 years presenting to the emergency department with non-fatal firearm injury; controls were 50 age and gender matched patients presenting with acute medical problems. OUTCOME MEASURE: Odds ratios (OR) and associated 95% confidence interval (CI) as estimates of the magnitude of association between risk factors and non-fatal firearm injury. RESULTS: After adjusting for age, gender and socioeconomic status, multivariate analysis identified four risk factors independently associated with firearm injury: living with less than two parents (OR 3.8, 95% CI 1.2 to 12.2), skipping class (OR 7.1, 95% CI 1.7 to 28.9), previous arrest (OR 6.2, 95% CI 1.9 to 20.7), and being African-American (OR 4.2; 95%CI 1.4 to 14.9). CONCLUSION: Risk factors for adolescents sustaining a non-fatal firearm injury are sociodemographic and environmental, not just behavioral. Thus interventions that foster protective and supportive environments may help prevent firearm injuries.

Adolescent↗
PubMed2001

Structure of the Bacillus cell fate determinant SpoIIAA in phosphorylated and unphosphorylated forms.

BACKGROUND: The asymmetric cell division during sporulation in Bacillus subtilis gives rise to two compartments: the mother cell and the forespore. Each follow different programs of gene expression coordinated by a succession of alternate RNA polymerase sigma factors. The activity of the first of these sigma factors, sigmaF, is restricted to the forespore although sigmaF is present in the predivisional cell and partitions into both compartments following the asymmetric septation. For sigmaF to become active, it must escape from a complex with its cognate anti-sigma factor, SpoIIAB. This relief from SpoIIAB inhibition requires the dephosphorylation of the anti-sigma factor antagonist, SpoIIAA. The phosphorylation state of SpoIIAA is thus a key determinant of sigmaF activity and cell fate. RESULTS: We have solved the crystal structures of SpoIIAA from Bacillus sphaericus in its phosphorylated and unphosphorylated forms. The overall structure consists of a central beta-pleated sheet, one face of which is buried by a pair of alpha helices, while the other is largely exposed to solvent. The site of phosphorylation, Ser57, is located at the N terminus of helix alpha2. The phosphoserine is exceptionally well defined in the 1.2 A electron density maps, revealing that the structural changes accompanying phosphorylation are slight. CONCLUSIONS: Comparison of unphosphorylated and phosphorylated SpoIIAA shows that covalent modification has no significant effect on the global structure of the protein. The phosphoryl group has a passive role as a negatively charged flag rather than the active role it plays as a nucleus of structural reorganization in many eukaryotic signaling systems.

Amino Acid Sequence↗
PubMed2001

Application of process chemistry and SAR modelling to the evaluation of health findings of lower olefins.

Epidemiology studies show increased leukemia mortality among styrene butadiene rubber (SBR) workers but not among butadiene monomer production employees. A detailed review of the SBR manufacturing process indicates that sodium dimethyldithiocarbamate (DMDTC) introduced into the SBR manufacturing process for a period in the 1950s coincides with increased leukemia mortality. Using the Computer-Optimized Molecular Parametric Analysis of Chemical Toxicity (COMPACT), we assessed the enzyme (cytochrome P450) substrate specificity of an olefin series including 1,3-butadiene (BD) and also modeled its interaction with DMDTC. These analyses showed correlation of a structural/electronic parameter--the COMPACT radius--with the presence or absence of cytogenetic activity and also found that DMDTC would inhibit the oxidative metabolism of BD at least at high concentrations. Both DMDTC and its diethyl analog (DEDTC) bind with CYP 2E1 and CYP 2A6. Both of these isoforms are important in the initial oxidative metabolism of butadiene and other olefins. In co-exposure studies in mice of DMDTC with BD or with epoxybutene (EB), we found that there was a reduced increase in genotoxic activity based on micronuclei induction compared with BD or EB exposure alone. Treatment with DMDTC significantly increased the protein carbonyl contents of hepatic microsomes compared with that of controls, a finding that may be related to DMDTC's activity as a prooxidant. Co-exposure with DMDTC and EB increased hepatic microsomal carbonyls to levels significantly greater than those of DMDTC-treated mice, while EB administration in the absence of DMDTC did not change protein carbonyls relative to those of controls. The increase in hepatic microsomal protein carbonyls suggests that DMDTC may modulate EB metabolism towards the formation of reactive intermediates that react with proteins. The present molecular modeling and mechanistic studies suggest that co-exposure of BD and DMDTC is a plausible biological hypothesis regarding increased leukemia risk among SBR workers.

Alkenes↗
PubMed2001

Crystal structure of GerE, the ultimate transcriptional regulator of spore formation in Bacillus subtilis.

The small, DNA-binding protein GerE regulates gene transcription in the terminally differentiated mother-cell compartment during late stages of sporulation in Bacillus subtilis. This versatile transcription factor shares sequence homology with the LuxR/FixJ/UhpA family of activators and modulates the expression of a number of genes, in particular those encoding the components of the coat that surrounds the mature spore. GerE orchestrates the final stages of coat deposition and maturation that lead to a spore with remarkable resistance properties but that must be responsive to low levels of germination signals. As this germination process is largely passive and can occur in the absence of de novo protein synthesis, the correct assembly of germination machinery, including germinant receptors and energy storage compounds, is crucial to the survival of the cell. The crystal structure of GerE has been solved at 2.05 A resolution using multi-wavelength anomalous dispersion techniques and reveals the nature of the GerE dimer. Each monomer comprises four alpha-helices, of which the central pair forms a helix-turn-helix DNA-binding motif. Implications for DNA-binding and the structural organisation of the LuxR/FixJ/UhpA family of transcription activator domains are discussed.

Amino Acid Sequence↗
PubMed2001

Cardiac morbidity and mortality following carotid endarterectomy: the importance of diabetes and multiple Eagle risk factors.

The objectives of this study were to (1) determine cardiac morbidity and mortality in patients undergoing carotid endarterectomy (CEA) and (2) to determine whether any Eagle risk factors and/or the indication for CEA are associated with a higher risk of an adverse cardiac event. The records of 123 male patients who underwent CEA were retrospectively reviewed. The Eagle risk factors for adverse cardiac events, indications for CEA, and adverse cardiac events were recorded and analyzed. In males undergoing CEA, the presence of diabetes or multiple Eagle risk factors significantly increases the risk of an adverse postoperative cardiac event. There is no difference in cardiac event rate between symptomatic and asymptomatic CEA. Thus, asymptomatic CEA should be approached with caution in these higher cardiac risk patients.

Aged↗
PubMed2001

Trends in cardiac morbidity and mortality after endoluminal abdominal aortic aneurysm repair; discussion 999-1000.

HYPOTHESIS: The adverse cardiac event rate following endoluminal abdominal aortic aneurysm (EAAA) repair has decreased as experience in performing the procedure has increased. Aneurysm complexity affects the rate of adverse cardiac events. DESIGN AND PATIENTS: Data from 173 consecutive patients undergoing EAAA repair from 2 successive periods were compared. There were 82 patients in the early group (group 1) and 91 patients in the later group (group 2). MAIN OUTCOME MEASURES: Myocardial infarction, congestive heart failure, unstable angina, major dysrhythmias, death. RESULTS: The cardiac event rate was 8.5% for group 1 vs 16.5% for group 2 (P =.16). Predictors of adverse cardiac events on multivariate analysis were the use of 4 or more graft extensions (P =.04), female sex (P =.01), and number of Eagle risk factors (P<.001). There were 2 postoperative deaths (2.4%) in group 1 and 4 (4.4%) in group 2 (P =.7). CONCLUSIONS: Following EAAA repair: (1) adverse cardiac events were found to correlate with use of 4 or more graft extensions, female sex, and the number of Eagle risk factors; (2) cardiac morbidity and mortality remain significant despite greater experience and improved technology; and (3) operative mortality remains acceptably low.

Aged↗
PubMed2001

Ciguatera fish poisoning in the Caribbean islands and Western Atlantic.

Ciguatera fish poisoning (ciguatera), a common poisoning caused by fish ingestion, is reviewed in the Western Atlantic and the Caribbean waters. It is endemic from Florida coasts (northern limit) to Martinique Island (southern limit), with outbreaks occurring from time to time. In the Caribbean, ciguatera causes a polymorphic syndrome with gastrointestinal, cardiovascular, and neurological signs and symptoms. Neurological and muscular dysfunctions can be treated by intravenous injection of D-mannitol. The lipid-soluble toxins involved are ciguatoxins that are likely produced by the dinoflagellate Gambierdiscus toxicus. G. toxicus strains are endemic in the Caribbean Sea and in theWestern Atlantic. Although it is likely that blooms of G. toxicus are ingested by herbivorous fishes, they are not implicated in ciguatera in the Caribbean. Rather, large carnivores (barracudas, jacks, snappers, groupers), consumers of smaller benthic fish, are often involved in ciguatera. Fish toxicity depends on fishing area and depth, fish size and tissues, and climatic disturbances. Ciguatoxins have been isolated and purified from Caribbean fish species. The structure of two epimers, C-CTX-1 and C-CTX-2 from horse-eye jack, comprise 14 trans-fused ether-linked rings and a hemiketal in terminal ring. Caribbean ciguatoxins are mainly detected in the laboratory by chicken, mouse, mosquito, or cell bioassays, and by analytical HPLC/tandem mass spectrometry down to parts per billion (ppb). A ciguatera management plan that integrates epidemiology, treatment, and a simple method of detection is required to ensure the protection of consumers.

Animals↗
PubMed2001

Initial nonoperative management for periappendiceal abscess.

PURPOSE: Our goal was to compare initial operative and nonoperative management for periappendiceal abscess complicating appendicitis. METHODS: This study is a retrospective review of 155 consecutive patients with appendicitis complicated by periappendiceal abscess treated between 1992 and 1998. Eighty-eight patients were treated initially nonoperatively, and 67 patients were treated operatively. All patients had localized abdominal tenderness and either computed tomography or intraoperative documentation of an abscess. RESULTS: Our patient population consisted of 107 males and 48 females, with an average age of 33 (range, 16-75) years. Age, gender, comorbidity, white blood cell count, temperature, and heart rate did not differ significantly between groups. For the initial nonoperative management group, the failure rate was 5.8 percent and the appendicitis recurrence rate was 8 percent after a mean follow-up of 36 weeks. The response to treatment of the initial nonoperative group and the initial operative group was compared by length of stay (9 +/- 5 days vs. 9 +/- 3 days; P = not significant), days until white blood cell count normalized (3.8 +/- 4 days vs. 3.1 +/- 3 days; P = not significant), days until temperature normalized (3.2 +/- 3 days vs. 3.1 +/- 2 days; P = not significant), and days until a regular diet was tolerated (4.7 +/- 4 days vs. 4.6 +/- 3 days; P = not significant). Complication rate was significantly lower in the nonoperative group (17 vs. 36 percent; P = 0.008). CONCLUSIONS: Initial nonoperative management of appendicitis complicated by periappendiceal abscess is safe and effective. Patients undergoing initial nonoperative management have a lower rate of complications, but they are at risk for recurrent appendicitis.

Abscess↗
PubMed2001

The changing face of ciguatera.

Ciguatera is a global disease caused by the consumption of certain warm-water fish (ciguateric fish) that have accumulated orally effective levels of sodium channel activator toxins (ciguatoxins) through the marine food chain. Symptoms of ciguatera include a range of gastrointestinal, neurological and cardiovascular disturbances. This review examines progress in our understanding of ciguatera from the work of Banner in the late 1950s to the present. Similarities and differences in ciguatera in the Pacific Ocean, Indian Ocean and Caribbean Sea are highlighted, and future research directions are suggested.

Animals↗
PubMed2001

Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter.

Cone snails use venom containing a cocktail of peptides ('conopeptides') to capture their prey. Many of these peptides also target mammalian receptors, often with exquisite selectivity. Here we report the discovery of two new classes of conopeptides. One class targets alpha1-adrenoceptors (rho-TIA from the fish-hunting Conus tulipa), and the second class targets the neuronal noradrenaline transporter (chi-MrIA and chi-MrIB from the mollusk-hunting C. marmoreus). rho-TIA and chi-MrIA selectively modulate these important membrane-bound proteins. Both peptides act as reversible non-competitive inhibitors and provide alternative avenues for the identification of inhibitor drugs.

Amino Acid Sequence↗
PubMed2001

Monitoring a clinical trial conducted under the Food and Drug Administration regulations allowing a waiver of prospective informed consent: the diaspirin cross-linked hemoglobin traumatic hemorrhagic shock efficacy trial.

In 1996, the US Food and Drug Administration (FDA) enacted Rule 21 CFR section 50.24, which allows a narrow exception to the requirement for prospective informed consent from human research subjects in clinical trials investigating potentially beneficial therapies for acute, life-threatening conditions. The first clinical trial to be conducted under this rule was sponsored by Baxter Healthcare Corporation and approved by the FDA on November 21, 1996. This large, multicenter, randomized clinical trial was designed to compare the addition of diaspirin cross-linked hemoglobin (DCLHb) with standard care in the initial resuscitation of adults experiencing severe, uncompensated, traumatic hemorrhagic shock. Before the first planned interim analysis of the data, review of fatal adverse events revealed an imbalance in mortality between the 2 treatment groups. The Data Monitoring Committee (DMC) recommended suspension of patient enrollment 24 days later. Additional data collection and analyses confirmed the excess number of deaths in patients treated with DCLHb but failed to reveal the cause of these deaths. The trial was formally terminated after only 112 of the planned 850 patients had been enrolled. We review the events leading up to and the rationale behind the DMC recommendations for suspension of patient enrollment and trial termination. Although the DCLHb trial was unsuccessful in achieving its goals, the monitoring process worked well. Emergency research was facilitated by DMC oversight, and the interests of research subjects were protected by the actions of the DMC.

Aspirin↗
PubMed2001

Outcome of out-of-hospital postcountershock asystole and pulseless electrical activity versus primary asystole and pulseless electrical activity.

OBJECTIVE: In the prehospital setting, countershock terminates ventricular fibrillation (VF) in about 80% of cases. However, countershock is most commonly followed by asystole or pulseless electrical activity (PEA). The consequences of such a countershock outcome have not been well studied. The purpose of this investigation was to compare the outcome of prehospital VF victims shocked into asystole or PEA with that of patients whose first documented rhythm was asystole or PEA (primary asystole or PEA). DESIGN: Observational, retrospective study conducted over 5 yrs (1995-1999). SETTING: A municipal hospital with a catchment area of >200,000. PATIENTS: Consecutive adult patients with out-of-hospital nontraumatic cardiopulmonary arrest of cardiac origin. Patients found in VF who developed asystole or PEA after countershocks (group 1) and patients found in asystole or PEA (primary asystole or PEA) (group 2) were included if the reported downtime was <10 min. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Study end points included restoration of circulation (defined as a pulse for any duration), survival to hospital admission, and survival to hospital discharge. Ratios were determined, 95% confidence intervals were calculated, and observed differences were compared. For group 1 patients (n = 101), 61% of patients had a bystander-witnessed collapse and 34% received bystander cardiopulmonary resuscitation. For group 2 patients (n = 140), collapse was bystander witnessed in 71% and 45% received bystander cardiopulmonary resuscitation. These differences were not statistically significant. Restoration of circulation was significantly more frequent in group 2 than group 1 (42% vs. 16%, p <.001) as was survival to hospital admission (36% vs. 11%, p =.001). Survival to hospital discharge was greater in group 2 patients, but the difference failed to achieve statistical significance (10% vs. 3%, p =.062). CONCLUSIONS: Countershock of prolonged VF followed by a nonperfusing rhythm has a worse prognosis than primary asystole or PEA and may be related to myocardial electrical injury.

Adult↗
PubMed2001

Crystallization and preliminary X-ray analysis of the sporulation factor SpoIIAA in its native and phosphorylated forms.

Sporulation in Bacillus begins with an asymmetric cell division producing two progeny with identical chromosomes but different developmental fates. As such, it is a simple example of cellular differentiation. The establishment of cell type is controlled by a series of alternate RNA polymerase sigma subunits. The first compartment-specific sigma factor is sigma(F), whose activity is controlled by SpoIIAB, an anti-sigma factor, and SpoIIAA, an anti-sigma factor antagonist which is phosphorylated by the kinase activity of SpoIIAB. Here, the preliminary crystallographic analysis of SpoIIAA and phosphorylated SpoIIAA from B. sphaericus in forms suitable for high-resolution structure determination are reported.

Bacillus↗
PubMed2001

An empirical analysis of stressors for gay men and lesbians.

This research describes the empirical classification of stressors for gay men and lesbians. Volunteer respondents were recruited through a free local gay and lesbian newspaper, through gay and lesbian student organizations nationwide, through gay and lesbian bookstores nationwide, and at a gay festival in St. Louis. Nine hundred seventy-nine (979) participants completed a 70-item measure with stressors that had been identified in previous qualitative research. Participants were asked to indicate the degree to which they had experienced stress associated with a variety of experiences. Participants also completed a measure of dysphoria (CES-D), responded about their degree of openness regarding sexual orientation, and provided information about their relationship status and involvement with gay groups and activities. Using confirmatory factor analysis, a six-factor model was predicted to account for the data. One-factor, six-factor, and ten-factor models were tested. The ten-factor model yielded the best fit with the data and accounted for 63.5% of the variance. The factor structure remained stable when gay men were compared to lesbians, when those endorsing a predominantly gay versus exclusively gay orientation were compared, and when those in a relationship were compared to those who were not in a relationship. Increased gay stress was associated with more dysphoria. Implications of these findings are discussed and directions for future research are considered.

Adult↗