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Biomedical subjects

C Lewis

Publications and source records attributed to C Lewis.

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

Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations.

Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis.

Alleles↗
PubMed2001

Devising an integrated methodology for analyzing energy use and CO2 emissions from Taiwan's petrochemical industries.

Input-output modeling and multiplier analysis are used to assess Taiwan's five petrochemical industries, based upon their economic contribution and potential impacts on energy consumption and CO2 emission. In addition, a consolidated index system was developed for evaluating energy and economic efficiencies as well as targets for CO2 reduction. Results indicate that petrochemical materials (PM) make a major contribution to economic development, with lesser contributions from plastic materials (PL) and artificial fibres (AF). PM has the highest energy multiplier while PL has the largest induced potential for energy consumption. Plastic and rubber products (PP, RP) are relatively insignificant energy consumers. AF has the highest CO2 multiplier, and its induced potential for CO2 emission is the most significant. The consolidated index shows that the upstream petrochemical industries perform rather poorly in an integrated view of economic, energy, and CO2 emission, and should be seen as the primary targets for CO2 reduction. Investment of the petrochemical industries in Taiwan should be adjusted to improve energy efficiency, economic bases, and lower CO2 emissions.

Carbon Dioxide↗
PubMed2001

An ergonomic evaluation of surgeons' axial skeletal and upper extremity movements during laparoscopic and open surgery.

BACKGROUND: Many surgeons have complained of fatigue and musculoskeletal pain after laparoscopic surgery. We evaluated differences in surgeons' axial skeletal and upper extremity movements during laparoscopic and open operations. METHODS: Five surgeons were videotaped performing 16 operations (8 laparoscopic and 8 open) to record their neck, trunk, shoulder, elbow, and wrist movements during the first hour of surgery. We also compared postprocedural complaints of pain, stiffness, or numbness between the two groups. RESULTS: Compared with surgeons performing open surgery, surgeons performing laparoscopic surgery exhibited less lateral neck flexion; less trunk flexion; more internal rotation of the shoulders; more elbow flexion; more wrist supination and wrist ulnar and radial deviation. There was a trend of more shoulder stiffness after laparoscopic operations than after open operations. CONCLUSIONS: Laparoscopic surgery involves a more static posture of the neck and trunk, but more frequent awkward movements of the upper extremities than open surgery. Ergonomic changes in the operating room environment and instrument design could ease the physical stress imposed on surgeons during laparoscopic operations.

Adult↗
PubMed2001

The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation.

BACKGROUND: Glycogen synthase kinase-3 (GSK-3) sequentially phosphorylates four serine residues on glycogen synthase (GS), in the sequence SxxxSxxxSxxx-SxxxS(p), by recognizing and phosphorylating the first serine in the sequence motif SxxxS(P) (where S(p) represents a phosphoserine). FRATtide (a peptide derived from a GSK-3 binding protein) binds to GSK-3 and blocks GSK-3 from interacting with Axin. This inhibits the Axin-dependent phosphorylation of beta-catenin by GSK-3. RESULTS: Structures of uncomplexed Tyr216 phosphorylated GSK-3beta and of its complex with a peptide and a sulfate ion both show the activation loop adopting a conformation similar to that in the phosphorylated and active forms of the related kinases CDK2 and ERK2. The sulfate ion, adjacent to Val214 on the activation loop, represents the binding site for the phosphoserine residue on 'primed' substrates. The peptide FRATtide forms a helix-turn-helix motif in binding to the C-terminal lobe of the kinase domain; the FRATtide binding site is close to, but does not obstruct, the substrate binding channel of GSK-3. FRATtide (and FRAT1) does not inhibit the activity of GSK-3 toward GS. CONCLUSIONS: The Axin binding site on GSK-3 presumably overlaps with that for FRATtide; its proximity to the active site explains how Axin may act as a scaffold protein promoting beta-catenin phosphorylation. Tyrosine 216 phosphorylation can induce an active conformation in the activation loop. Pre-phosphorylated substrate peptides can be modeled into the active site of the enzyme, with the P1 residue occupying a pocket partially formed by phosphotyrosine 216 and the P4 phosphoserine occupying the 'primed' binding site.

Amino Acid Motifs↗
PubMed2001

Sex, drugs, and hypertension: a methodological approach for studying a sensitive subject.

Sexual dysfunction is a recognized side effect of hypertension and antihypertensive medications in men, but is not established as a side effect in women, due to the lack of established methodology. An ambulatory medical record-based, case-control study was designed to study sexual function in treated and untreated hypertensive women and healthy controls. The research was performed in a teaching hospital with satellite clinics in upstate New York. There were 3312 medical records reviewed, 640 premenopausal Caucasian women in heterosexual relationships subjects were eligible for participatic diagnosis of mild hypertension (BP > or =140/90 mmHg and < 160/100 mmHg) for cases; no other significant medical history. A total of 241 women agreed to participate, 224 (35%) completed both a self-administered questionnaire and a telephone interview (112 healthy, 112 hypertensive). There was an initial 74% response rate among those eligible to participate, with 35% completing the entire study. Age and average blood pressure were not significant between 224 participants and 416 nonparticipants by 2-tailed t-test analysis. Seven composite variables were formed from a 47-item sexual response questionnaire. Initial unadjusted chi2 results reported women with hypertension had more difficulty than did healthy controls achieving lubrication and orgasm. Seven questions, each with the highest correlation to its respective composite variable (by Spearman's correlation), formed an abbreviated questionnaire. Quality of female sexual function was quantified in an ambulatory outpatient setting. A method was described to address hypertension, pharmacotherapy, and sexual functioning by employing self-administered questionnaires and telephone interviews. Initial analysis suggested that hypertensive women may have an impaired physiological sexual response. The abbreviated questionnaire generated from questions with the highest correlation to their respective composite variables may be useful in further evaluating this issue.

Adult↗
PubMed2001

IL-4, IL-13, and dexamethasone augment fibroblast proliferation in asthma.

BACKGROUND: IL-4 and IL-13 have been shown to be critical for expression of the asthma phenotype in a murine model and may modulate human fibroblast function. OBJECTIVE: We hypothesized that IL-4 and IL-13 would increase airway fibroblast proliferation and reduce the ability of dexamethasone to decrease this proliferation. METHODS: Six subjects with severe asthma, 5 subjects with mild asthma, and 5 healthy subjects underwent bronchoscopy with endobronchial biopsy. Biopsy specimens were placed in Dulbecco modified Eagle medium and cultured, and only fibro-blasts from the first and second passages were evaluated. Cells were incubated with IL-4 (50 ng/mL), IL-13 (10 ng/mL), and the combination for 48 hours in the presence and absence of dexamethasone, 10(-7) mol/L, and 10(-8) mol/L. Fibroblasts were also incubated with IFN-gamma at 50 ng/mL to assess the response of a T(H)1 cytokine on proliferation. RESULTS: Fibroblast proliferation, determined by (3)H-thymidine incorporation, was significantly increased by IL-4 in subjects with mild asthma as compared with IL-4 in subjects with severe asthma and healthy subjects (P =.003), IL-13 (P =.011), and the combination (P =.004). Dexamethasone also increased proliferation in the group with mild asthma as compared with the group with severe asthma and the healthy group (10(-7) mol/L, P =.02; 10(-8) mol/L, P =.02). IFN-gamma did not significantly alter airway fibroblast proliferation. CONCLUSION: IL-4, IL-13, and dexamethasone all significantly increased fibroblast proliferation in subjects with mild asthma.

Adult↗
PubMed2001

Hypoxic upregulation of TNF receptor type 2 expression involves NF-IL-6 and is independent of HIF-1 or HIF-2.

Tumor necrosis factor (TNF) exerts its biologic activity via two distinct membrane receptors, TNF receptor type 1 (p55TNFR) and TNF receptor type 2 (p75TNFR). Whereas the p55TNFR gene is rather constitutively expressed, transcription of p75TNFR is strongly modulated by a number of stimulatory agents. Experimental evidence suggested the involvement of p75TNFR in endothelial cell activation. Therefore, we have tested the transcriptional activity of p75TNFR under conditions of hypoxia and reoxygenation. Northern blot analysis revealed that p75TNFR mRNA is upregulated in NIH3T3 cells under hypoxia and reoxygenation. This observation directly originates from transcriptional activation of the p75TNFR gene, as shown by reporter gene analysis. Cotransfection experiments clearly showed that the transcriptional induction of the p75TNFR gene is independent of the hypoxia-induced factors, HIF-1alpha and HIF-2alpha. Using deletion mutants of the 5'-flanking region of the p75TNFR gene, we were able to identify a putative DNA binding site for the transcription factor nuclear factor-interleukin-6 (NF-IL-6) to be responsible for the transcriptional upregulation of the p75TNFR gene under conditions of hypoxia and reoxygenation.

3T3 Cells↗
PubMed2001

Changes in health care providers' knowledge, attitudes, beliefs, and behaviors regarding domestic violence, following a multifaceted intervention.

PURPOSE: To improve domestic violence (DV) identification, management, and referral in a not-for-profit rural health network, training for health care professionals was implemented using a train-the-trainer approach, two one-hour training sessions, and dissemination of a clinical protocol. The multifaceted approach also involved modifications of emergency department medical records, distribution of office enablers, and a local public health campaign. The authors measured the effectiveness of this campaign. METHODS: After implementation of a multifaceted training and public awareness campaign, a questionnaire designed by the Centers for Disease Control to measure knowledge, attitudes, beliefs, and intended behaviors (KABB) of health care providers relative to DV was administered to 380 health care professionals in the fall of 1997, with a follow-up survey completed after the intervention in the fall of 1999. RESULTS: The response rates for the pre- and post-intervention surveys were 67% (n = 380) and 56% (n = 273), respectively. Two scales were correlated in the base-line survey: self-efficacy (related to DV response) and familiarity with referral resources. Reporting of victim identification in the preceding year increased from 36% to 39%. Those with training were more likely to have identified a victim within the year (OR = 2.86; 95% CI, 1.73-4.74). Among the 232 respondents with complete data, multiple analysis of variance demonstrated statistically significant overall improvement across all scales. Nine of the 13 KABB scales revealed significant increases from pre- to posttest and included: screening, workplace resources, making referrals, provider self-efficacy, victim autonomy, victim understanding, legal requirements, staff preparation, and too busy/can't help. CONCLUSION: A comprehensive training program for health care providers can increase their self-efficacy in responding to DV victims.

Adult↗
PubMed2001

Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors.

SB-219383 and its analogues are a class of potent and specific inhibitors of bacterial tyrosyl-tRNA synthetases. Crystal structures of these inhibitors have been solved in complex with the tyrosyl-tRNA synthetase from Staphylococcus aureus, the bacterium that is largely responsible for hospital-acquired infections. The full-length enzyme yielded crystals that diffracted to 2.8 A resolution, but a truncated version of the enzyme allowed the resolution to be extended to 2.2 A. These inhibitors not only occupy the known substrate binding sites in unique ways, but also reveal a butyl binding pocket. It was reported that the Bacillus stearothermophilus TyrRS T51P mutant has much increased catalytic activity. The S. aureus enzyme happens to have a proline at position 51. Therefore, our structures may contribute to the understanding of the catalytic mechanism and provide the structural basis for designing novel antimicrobial agents.

Amino Acid Sequence↗
PubMed2001

Impact of a rural domestic violence prevention campaign.

Domestic violence is a prevalent health problem that in rural areas is further complicated by limited services, social isolation and the lack of privacy. Little is known about the impact of public health education on awareness, attitudes and behavior of the general public regarding domestic violence. This study sought to measure change in societal attitudes and behavioral intention in response to a seven-month public health education campaign targeting domestic violence in a rural county. From October 1998 to April 1999, the campaign used radio advertisements, posters, mailings to libraries and clergy, printed media articles, printed advertisements and health facility modifications. A random-digit-dialing telephone survey was used to evaluate attitudinal and behavioral changes in the intervention and comparison counties before and after the campaign. The response rates for the pre- (n =378) and postcampaign (n=633) surveys were 73 percent and 65 percent, respectively. Statistically significant increases in slogan and advertising recognition occurred in the intervention county (P=0.03), particularly among men recalling the campaign slogan (P=0.006). In a vignette regarding actions to be taken if the neighbor next door was abusing a partner, significant increases occurred in the intervention county in the percentage of respondents who thought that most people would talk to the victim (P=0.04), consult with friends (P=0.002) or talk to a doctor (P=0.004). Domestic violence agency hotline calls in the intervention county doubled following the campaign. Local public health education campaigns in a rural setting may be a valuable adjunct to national efforts, especially in reaching men.

Adolescent↗
PubMed2001

Oral health status of adults from a California regional center for developmental disabilities.

The oral health status and treatment needs of developmentally disabled adults (18 years and older) from a Los Angeles Regional Center who live in a variety of settings were measured as part of a comprehensive study to determine their overall health status. A dental assessment was performed on a sample of 325 persons which was similar in demographic composition to the entire population at the center. Approximately 80% of clients reported a personal dentist of record, and 73% brushed their own teeth. Edentulism was 9%. The mean number of retained teeth per person was 22. Subjectively, 15.7% of the sample was rated as having "good" overall dental health, 77.7% "fair," and 6.6% "poor." The major reasons rendering fair or poor assessments were oral hygiene, clinical periodontal disease, and dental caries. More females than males were assessed as having "good" overall dental health. The overall appearance of the teeth for a majority of the sample (76.5%) was rated as "same as most." Persons who brushed their own teeth had fewer missing teeth than those who did not. Persons with a dentist of record had fewer decayed and more filled teeth. Persons living at home with family or friends had a significantly lower DMFT index than those living independently or in facilities. In general, these findings are encouraging; however, caution must be exercised, since efforts to improve the oral health status of this population require continued attention.

Adult↗
PubMed2001

A two-source model for electron beams: calculation of relative output factors.

A two-source model for the calculation of relative output factors (ROF) for clinical applications of electron beams has been developed. The model consists of (1) an effective extended source above the final field-defining aperture (cutout) plane and (2) a source due to scattering from the aperture. Calculations are based on Fermi-Eyges theory and a pencil beam algorithm with parameters determined independently for each major scattering component. The model predicts a modified inverse square law for determining the dose rate for the electron beams. It also generalizes the "square-root method" and "one-dimensional method" that are often used clinically for ROF calculations. A computer program based on the model has been developed to calculate ROF for irregular fields. The predictions of ROF values have been compared with measurements on a Varian CLINAC 2100C/D accelerator for different cutout size, energies, applicators, and SSDs for square fields, rectangular fields, circular fields, and irregular fields. The agreement between prediction and measurement of the ROF for these wide range of conditions is generally within 1% for energies from 6 to 20 MeV. This two-source model can be used for clinical applications and it requires a minimal set of measured input data.

Algorithms↗
PubMed2001

A normative reference database study for Pronosco X-posure System.

Cortical width from radiographs has been used for more than 40 yr as a means of estimating bone strength. In the last 5-10 yr, increased availability of computers and the development of automated algorithms for image assessment have led to an increased interest in radiogrammetry. In this study, we examined a new radiogrammetry device, the Pronosco X-posure System, which estimates bone mineral density (BMD) from forearm/hand radiographs. We obtained hand and forearm radiographs and performed dual X-ray absorptiometry (DXA) at the wrist and hip on 832 women ages 20-79 at four clinical centers across the United States. We then used the X-posure System to estimate BMD (DXR-BMD). The goal of the study was to establish reference ranges for the method and to compare the measurement to DXA measurements of BMD at the wrist and hip. Using statistical models, we estimated that the peak value for DXR-BMD occurred at age 38 (mean = 0.598 g/cm2, standard deviation = 0.034 g/cm2). The correlation between DXR-BMD and DXA was 0.90 at the wrist and 0.61 at the hip. The relationship of DXR-BMD to reported history of fracture was of similar magnitude to that for DXA at the wrist and hip. The strong correlation of DXR-BMD from the X-posure System with DXA at the wrist from the Hologic machine suggests that the X-posure System may be an alternative to DXA at the wrist for the assessment of osteoporosis.

Absorptiometry, Photon↗
PubMed2001

The lifetime cost of bipolar disorder in the US: an estimate for new cases in 1998.

OBJECTIVE: To develop a cost model that estimates the total and per case lifetime cost of bipolar disorder for 1998 incident cases in the US. STUDY DESIGN: Lifetime cost simulation model. PERSPECTIVE: Societal. METHODS: Age- and gender-specific incidence of bipolar disorder in 1998 was estimated by simulation based on existing prevalence data. The course of illness and mental health service cost of 6 clinically defined prognostic groups was estimated based on the research literature and the judgement of panels of experts. Excess cost of general medical care was estimated based on claims data from a large insurer. Indirect cost was projected including excess unemployment and reduced earnings reported in the National Comorbidity Survey. Comorbidity treatment and indirect cost related to alcohol (ethanol) and drug abuse was added based on a National Institute on Drug Abuse study. RESULTS: The present value of the lifetime cost of persons with onset of bipolar disorder in 1998 was estimated at 24 billion US dollars ($US). Average cost per case ranged from $US11,720 for persons with a single manic episode to $US624,785 for persons with nonresponsive/chronic episodes. CONCLUSION: The model indicates the potential cost savings of preventing a case of bipolar disorder and underscores the importance of achieving a stable outcome in new cases to limit the economic consequences of the disorder.

Adolescent↗