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At least 649 records · Page 36Linked to original sources
PubMed2005

Role of resistin in obesity, insulin resistance and Type II diabetes.

Resistin is a member of a class of cysteine-rich proteins collectively termed resistin-like molecules. Resistin has been implicated in the pathogenesis of obesity-mediated insulin resistance and T2DM (Type II diabetes mellitus), at least in rodent models. In addition, resistin also appears to be a pro-inflammatory cytokine. Taken together, resistin, like many other adipocytokines, may possess a dual role in contributing to disease risk. However, to date there has been considerable controversy surrounding this 12.5 kDa polypeptide in understanding its physiological relevance in both human and rodent systems. Furthermore, this has led some to question whether resistin represents an important pathogenic factor in the aetiology of T2DM and cardiovascular disease. Although researchers still remain divided as to the role of resistin, this review will place available data on resistin in the context of our current knowledge of the pathogenesis of obesity-mediated diabetes, and discuss key controversies and developments.

Amino Acid Sequence↗
PubMed1996

Ethics and the police surgeon: compromise or conflict?

Police surgeons play an important role in the British criminal justice system. Professionally located between the two worlds of medicine and the law, they face ethical dilemmas which derive from the dual nature of their role. The development of the police surgeon service has seen the emergence of three further dualisms within the police surgeon role. These are the forensic-therapeutic divide, the specialist-generalist division, and the issue of dependence or independence with regard to the police. These internal dualisms are discussed and their implications explored. Attention then turns to a consideration of three issues which demonstrate the nature of the ethical dilemmas facing the British police surgeon: the particular articulation of the (police) doctor-patient relationship, the matter of consent, and the subject of confidentiality. Both these ethical issues and the nature of the police surgeon role are explored through the primary analysis of survey and interview data collected from a national sample of police surgeons and police services, and the secondary analysis of key documents on the police surgeon, the paper concludes that specific ethical guidance is needed to address the forensic aspects of the police surgeon role.

Confidentiality↗
PubMed2002

Array-based structure and gene expression relationship study of antitumor sulfonamides including N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide and N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide.

Compounds from sulfonamide-focused libraries have been evaluated in cell-based antitumor screens using the COMPARE analysis with a panel of 39 human cancer cell lines and flow cytometric cell cycle analysis. Thus far, 2 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide (E7010)) and 3 (N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide (E7070)) have been selected from the collections as potent cell cycle inhibitors, which have progressed to clinical trials. Compound 2 is an orally active antimitotic agent disrupting tubulin polymerization, whereas compound 3 belongs to a novel class of antiproliferative agents causing a decrease in the S phase fraction along with G1 and/or G2 accumulation in various cancer cell lines. Because both compounds exhibited preliminary clinical activities in the phase I setting, we decided to examine further this series of oncolytic small molecules, particularly by using high-density oligonucleotide microarray analysis. The array data have enabled us to characterize these two classes of antitumor sulfonamides on the basis of gene expression changes, illuminating the essential pharmacophore structure and drug-sensitive cellular pathways for each class. Moreover, the dual character of 5 (N-(3-chloro-7-indolyl)-4-methoxybenzenesulfonamide (ER-67880)), resembling both 2 and 3, was revealed by array-based transcription profiling, though the 3-type profile of this molecule had not been apparent in the cell-based phenotypic screens. These results provide an example of the utility of structure and gene expression relationship studies in medicinal genomics.

Algorithms↗
PubMed2005

Principal component analysis calibration method for dual-luminophore oxygen and temperature sensor films: application to luminescence imaging.

Oxygen sensor films are frequently used to image air-pressure distributions on surfaces in aerodynamic wind tunnels. In this application, the sensor film is referred to as a pressure-sensitive paint (PSP). A Stern-Volmer calibration is used to relate the emission intensity ratio of a long-lifetime luminescent dye (the pressure-sensitive luminophore, PSL) to surface air pressure. A major problem in PSP measurements arises because the Stern-Volmer calibration of the PSL's emission varies with temperature. To correct for the temperature dependence, a second luminescent dye that has an emission that varies with temperature (the temperature-sensitive luminophore, TSL) is incorporated into the sensor film. With such a dual-luminophore PSP (DL-PSP), it is possible to measure the surface-temperature distribution with the TSL emission, and this information is then used to correct the temperature dependence of the PSL's pressure response. In the present article, we report the application of a DL-PSP to obtain high-resolution air-pressure distributions on a surface that is subjected to a 20 degrees C temperature gradient. Two different calibration methods are used to generate surface-temperature and air-pressure distributions from the luminescence imaging data, and a quantitative comparison of the results obtained from the two methods is provided. The first method is based on an intensity-ratio calibration that uses luminescence images collected at two wavelengths, one corresponding to the TSL emission and the second corresponding to the PSL emission. The second method is based on principal component analysis (PCA) of luminescence images obtained at four wavelengths throughout the spectral region of the TSL and PSL emission (hyperspectral imaging, 550-750 nm). The results demonstrate that the PCA method allows the measurement of surface air pressure with higher accuracy and precision compared to those of the intensity-ratio method. The improvement is especially significant at pressures near 1 atm, where the temperature interference is most pronounced. Surface-pressure distributions are measured with comparable accuracy and precision with the two methods.

Journal Article↗
PubMed1995

Regional Study of Care for the Dying: methods and sample characteristics.

The Regional Study of Care for the Dying (RSCD) was established in 1990 with the dual aims of providing district health authorities with an audit of local services for the dying, and of addressing questions about experiences of people dying from cancer, effectiveness of hospice care, and needs of and appropriate service provision for people dying from causes other than cancer. The survey methods are described in this paper, together with the characteristics and representativeness of the sample. An interview survey was conducted of family or others who knew about the last year of life of a random sample of people who died in 1990. It was based upon methods used in nationally representative surveys by Cartwright in 1969, and Cartwright and Seale in 1987. The setting was 20 district health authorities, who paid for local data collection. Approximately 270 deaths were randomly sampled in each district: 5375 deaths were sampled in total. As cancer patients are the focus of most services for the dying, cancer deaths were sampled disproportionately (54%). Interviews were obtained for 69% (3696) of the sample. The response rate varied significantly by cause of death, age and social class of decreased, and the degree of deprivation of the district. There were small, but statistically significant, differences in cause of death and age between those deaths for whom interviews were obtained and national figures for deaths occurring in 1990. The discussion addresses key issues in the study, including responses from ethical committees, response rate and quality of data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2004

Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma.

BACKGROUND AND OBJECTIVES: Bone lesions often occur in multiple myeloma (MM), but no tests have proven useful in identifying patients with increased risk. Bone marker assays and bone densitometry are non-invasive methods that can be used repeatedly at low cost. This study was performed to evaluate these methods in predicting bone events in MM patients. DESIGN AND METHODS: Thirty newly diagnosed MM patients were enrolled. Serum C-terminal telopeptide (ICTP) and urinary N-terminal telopeptide (NTx) of collagen I were measured for assessment of bone resorption, and serum C-terminal (PICP) and N-terminal (PINP) propeptides of procollagen I, bone-specific alkaline phosphatase, and osteocalcin were measured to estimate bone formation. Dual energy X-ray absorptiometry (DEXA) was used to assess bone mineral density (BMD) of the lumbar spine, hip, and whole body. Serum and urine samples were collected every 6 weeks, DEXA-scans performed every 3 months, and skeletal radiographs were done every 6 months as well as when indicated. RESULTS: Serum ICTP and urinary NTx were predictive of progressive bone events. Markers of bone formation, bone mineral density assessments, and M component measurements were less informative. In Cox analysis, ICTP showed the highest predictive value, but should be replaced with NTx in patients with nephropathy. Pretreatment low lumbar BMD was predictive of early vertebral fractures. INTERPRETATION AND CONCLUSIONS: Sequential DEXA-scans showed heterogeneous local BMD changes, and our data do not support routine use of sequential DEXA-scans. However, lumbar DEXA-scans at diagnosis can identify patients with increased risk of early vertebral collapses. Sequential analyses of serum ICTP and urinary NTx are useful for monitoring bone damage.

Absorptiometry, Photon↗
PubMed1997

Toward the validation of aneusomy detection by fluorescence in situ hybridization in bladder cancer: comparative analysis with cytology, cytogenetics, and clinical features predicts recurrence and defines clinical testing limitations.

Fluorescence in situ hybridization (FISH) is regarded as a potential new tool for the clinical management of bladder cancer that works by detecting cytogenetic aberrations in noncycling, exfoliated cells from bladder irrigations. However, clinical validation steps must be addressed to define the true predictive potential in a clinical setting. Toward the validation of FISH with the use of bladder washings and prior to incorporation into a large, prospective clinical trial, a pilot study was designed to determine its clinical potential, define testing limitations, optimize a panel of probes specific for bladder cancer detection, and outline protocol/data collection parameters. Correlations with standard cytogenetics and clinicopathological features of bladder cancer were investigated. Exfoliated cells obtained from benign bladder washings served as normal controls. The results of this pilot study suggest the following: (a) FISH and cytology are complementary testing procedures; however, the FISH data provided valuable ploidy and specific genotypic information for recurrent tumors in "suspicious" cases; (b) chromosomal aberrations defined by FISH are associated with tumor grade and stage (i.e., simple numerical aberrations were associated with low-grade tumors, and high-grade and invasive tumors exhibited multiple, nonrandom chromosomal aberrations and vast intratumor heterogeneity); (c) somatic pairing or homologous centromeric association can give a false-positive result and appears to be linked to prior therapy; (d) dual hybridization with reference gene-specific probes must be used to control for somatic pairing; and (e) focal, deep muscle invasive lesions, with no surface exposure, may yield false-negative results. The data suggest that FISH analysis, with the use of cells isolated from bladder washings, is a powerful technique holding promise for early cancer detection, monitoring treatment outcome, and predicting recurrence of disease.

Aneuploidy↗
PubMed2004

Gabapentin reduces cocaine use among addicts from a community clinic sample.

BACKGROUND: Individuals with chronic psychiatric conditions display a high rate of cocaine use. Gabapentin was hypothesized to reduce cocaine use by restoring inhibitory GABAergic feedback on ascending dopaminergic projections to nucleus accumbens neurons. METHOD: Nine participants with DSM-IV cocaine dependence were selected from patients attending a large community psychiatric clinic. During a 24-week open-label trial of gabapentin (800-2400 mg/day), qualitative urine drug screens were collected from the participants up to 3 times per week. Data were collected from September 1999 to May 2001. RESULTS: With gabapentin, the mean +/- SD number of cocaine-positive urine screens decreased from 53.11 +/- 13.23 to 35.22 +/- 14.84 (t = 3.58, N = 9, p <.01). The number of weeks of abstinence from cocaine increased from 2.1 +/- 1.5 to 8.0 +/- 5.5 (t = 3.21, N = 9, p <.01). CONCLUSION: Gabapentin appeared to be a safe and efficacious medication to reduce cocaine usage in a community sample of psychiatric patients.

Acetates↗
PubMed1999

Mode of infant feeding and achieved growth in adolescence: early feeding patterns in relation to growth and body composition in adolescence.

OBJECTIVE: Feeding mode in infancy and differences in childhood growth have been studied in several longitudinal studies, but few studies have followed children up to adolescent age. There is evidence that formula-fed infants weigh more and are taller than their breast-fed counterparts, and indications that this difference may sustain. RESEARCH METHODS AND PROCEDURES: We have studied the relations between length of breast-feeding, growth, and body composition in a group of 781 representatively chosen adolescents. Data on feeding pattern in infancy and on weight and height from birth up to 18 years were collected. We studied the relation between high body mass index (BMI) (defined as < or =85th percentile) in adolescence and length of breast-feeding. RESULTS: Girls who were not breast-fed or breast-fed for less than 3 months had a significantly higher height curve than girls exclusively breast-fed for more then 3 months. There were tendencies towards higher values of adipose tissue measured by skinfolds in girls breast-fed for 3 months or less. Short duration of exclusive breast-feeding was associated with higher BMI (p<0.04). In a subgroup of 194 adolescents, body composition was measured with dual energy X-ray. Both boys and girls who were exclusively breast-fed for more than 3 months were leaner and showed a trend towards lower skinfold values. CONCLUSION: These results are important to include in the debate about optimal feeding in infancy. Regarding breast-feeding as a standard, our results imply that formula fed infants may be at risk for overfeeding, which might lead to overweight, even up to adolescent age.

Absorptiometry, Photon↗
PubMed2005

Accuracy of WAAS-enabled GPS for the determination of position and speed over ground.

The Global Positioning System (GPS) offers many advantages over conventional methods for the determination of subject speed during biomechanical studies. Recent advances in GPS technology, in particular the implementation of the Wide-Angle Augmentation System and European Geostationary Navigation Overlay Service (WAAS/EGNOS), mean that small, highly portable units are available offering the potential of superior accuracy in the determination of both position and speed. This study set out to examine the accuracy of a WAAS-enabled GPS unit for the determination of position and speed. Comparison with the new and published data showed significant enhancements in both position and speed accuracy over a non-WAAS system. Position data collected during straight line cycling showed significantly lower sample-to-sample variation (mean absolute deviation from straight line 0.11 vs. 0.78 m) and greater repeatability from trial to trial (mean absolute deviation from actual path 0.37 vs. 4.8 m) for the WAAS-enabled unit compared to the non-WAAS unit. The speed determined by the WAAS-enabled GPS receiver during cycling in a straight line was within 0.2 ms(-1) of the actual speed measured for 57% of the values with 82% lying within 0.4 ms(-1), however, the data tended towards underestimation of speed during circle cycling, with 65% of values within 0.2 ms(-1) and 87% within 0.4 ms(-1) of the actual value. Local dGPS and dual frequency techniques are more accurate still, however, traditional differential GPS (dGPS), employing FM radio transmission of correction data to a separate receiver, now offers no advantage over WAAS and appears redundant.

Bicycling↗
PubMed1998

Sex differences in selection of pacemakers: retrospective observational study.

OBJECTIVE: To evaluate the effect of patients' sex on selection of pacemakers. DESIGN: Retrospective univariate and multivariate analysis of a large database. SETTING: German central pacemaker register. SUBJECTS: Records collected at the register for 1992 and 1993 (n=31 913), covering 64% of all implantations in Germany. MAIN OUTCOME MEASURE: Probability of receiving a single chamber, dual chamber, or rate responsive pacemaker in relation to sex. RESULTS: Univariate analysis showed that women were more likely to receive single chamber pacemakers and less likely to receive dual chamber or rate responsive systems than men. After demographic and clinical variables were controlled for, women were still more likely to receive a single chamber system (atrial pacing: odds ratio 0.89, 95% confidence interval 0.74 to 1.07; ventricular pacing: 0.85, 0.80 to 0.92) and less likely to receive a dual chamber (1.20, 1.12 to 1.30) or a rate responsive system (1.26, 1.17 to 1.37) than men. CONCLUSIONS: The data suggest sex differences in the selection of a pacemaker system which cannot be explained by the underlying cardiac disorder. Further research is needed to evaluate why guidelines for implanting pacemakers are not better adhered to.

Aged↗
PubMed1978

Evidence for a dual mechanism of lipolysis activation by epinephrine in rat adipose tissue.

Whole homogenates prepared from tissue previously exposed to epinephrine displayed a 3-fold increased rate of lipolysis of endogenous substrate. When the aqueous infranatant phase of such homogenates was collected by centrifugation and assayed against exogenous triolein emulsions, no hormone effect could be demonstrated. Treatment of such infranatants with cAMP-dependent protein kinase prepared from muscle increased their lipase activity against exogenous triolein by 80%. Employing [3H]triolein emulsions as exogenous substrate, rates of lipolysis of both endogenous and exogenous glycerides were measured simultaneously in whole tissue homogenates. Prior treatment of the tissue with epinephrine increased the rate of lipolysis of endogenous glycerides an average of 3-fold but had no effect on the hydrolysis of exogenous triolein. By contrast, treatment of whole homogenates with protein kinase accelerated lipolysis of exogenous triolein without altering the rate of hydrolysis of endogenous glycerides. The data suggest that a second pathway of lipolysis activation occurs in response to epinephrine in addition to that involving a cAMP-mediated increase in the state of phosphorylation of the hormone-sensitive lipase.

Adipose Tissue↗
PubMed2002

Mycobacterium bovis BCG cell wall and lipopolysaccharide induce a novel gene, BIGM103, encoding a 7-TM protein: identification of a new protein family having Zn-transporter and Zn-metalloprotease signatures.

To identify novel genes induced during innate immune activation, we screened a cDNA library prepared from monocytes stimulated with Mycobacterium bovis BCG cell wall. A novel transcript with three-protein coding potential was identified, and the expressed proteins from individual frames showed distinct intracellular localization. Live and heat-killed Mycobacterium, bacterial cell wall, and inflammatory cytokines like TNFalpha were found to be potent inducers of the transcript. Expression of this gene is very low or undetectable in unstimulated monocytes, while a steady expression level was observed during differentiation of monocytes to dendritic cells and macrophages. The entire gene consisted of eight major exons and was localized on chromosome 4q22-q24, spanning approximately 84 kb. The main open reading frame of the transcript encoded a putative seven-transmembrane (TM) protein that showed homology with a number of functionally unknown proteins in the database. Further analysis revealed that all of these proteins have detectable similarity with the ZIP family of metal transporters. In fact, increased accumulation of intracellular Zn(2+) was observed due to the expression of BIGM103 in CHO cells. However, the identified proteins are structurally unique compared to known ZIP members and they also possess the hallmark of Zn-metalloproteases, suggesting a new class of multi-TM protein with dual features. Here we present a collection of these proteins and discuss the functional aspects of BIGM103, based on our results and current findings on two members of the family, Drosophila Catsup and Arabidopsis IAR1.

Amino Acid Sequence↗
PubMed2004

A preliminary comparison of levalbuterol and albuterol in prehospital care.

Nebulized levalbuterol has been documented as more efficacious than albuterol in enhancing airflow in Emergency Department (ED) patients with bronchospasm. This work attempts to determine if nebulized levalbuterol yields similar improvements in peak flow measurements as those produced by albuterol in the Emergency Medical Services (EMS) arena. All adult EMS patients given a nebulized beta-agonist from January to June 2000 were included in this prospective, before-and-after, open-label study. Data collected included demographics, initial peak expiratory flow (PF), and use of home inhaled or nebulized bronchodilators before EMS arrival (PRE-TX). Outcome variable was the change in PF after a single EMS treatment with one of the study agents. Statistical analysis was performed using t-test and chi-square techniques; p was defined as 0.05. There were 298 patients enrolled; complete data for analysis were available for 196. Mean age was 68.0 years; 44.4% were male. Overall, albuterol produced a PF change of 19.7%; levalbuterol yielded a change of 20.4% (p = 0.9). In contrast to ED data, levalbuterol and albuterol produces similar changes in PF in the prehospital setting. Explanations for this finding may be linked to the pharmacokinetics of single vs. dual isomer preparations, and to the time frames of EMS care. Further efforts correlating EMS and ED data may better define the use of levalbuterol in prehospital care.

Administration, Inhalation↗
PubMed1999

Nursing in the nineties: managing the uncertainty.

OBJECTIVE: This study examined qualitative data on nurses' work lives from 53 hospitals that participated in the National Institutes of Health (NIH)-funded Outcomes Research in Nursing Administration Project (ORNA). BACKGROUND: The ORNA project examines the impact of nursing unit organizational structure on outcomes. The information reported in this article amplifies the quantitative data with qualitative data that enhances understanding of nurses' work lives. METHODS: Site coordinators at all participating hospitals were requested to send monthly journal entries for 6 months. Data were documented according to an agreed-on content outline that consisted of critical incidents and implications. Data were collected from 53 of the 65 study site coordinators (response rate 81.5%). Content analysis of all collected data was conducted by the research team. RESULTS: Study site coordinators in 53 hospitals characterize the acute care environment as turbulent and uncertain. Contributing factors include: 1) work load (fluctuating census, staff preparation, turnover); 2) loss of workplace identity (unit consolidation, hospital buy-outs, and system mergers); and 3) re-engineering (skill mix, new equipment/system changes, new documentation systems, rumored changes). CONCLUSIONS: This study adds to the growing body of literature that portrays environmental uncertainty from the narrative perspective. Although there is an ongoing need for the employment of fiscally accountable, quality enhancing organizational/management strategies, all initiatives are at risk unless personnel needs are attended to and seen as unique in each care setting. Some strategies are offered to meet this dual imperative.

Attitude of Health Personnel↗
PubMed2002

HER-2/neu-derived peptide epitopes are also recognized by cytotoxic CD3(+)CD56(+) (natural killer T) lymphocytes.

The human HER-2/neu gene encodes a 185 kDa transmembrane glycoprotein recognized by MHC class I-restricted CTLs. Here, we report that HER-2/neu peptide CTL epitopes can also be recognized by cytotoxic NK-T lymphocytes. Unfractionated peptides derived from HLA-A2(+), HER-2/neu(+) tumor cells acid cell extract (ACE), collected from patients with metastatic ovarian cancer, were used as antigen to generate in vitro cytotoxic effectors. ACE was able to elicit from cancer patients' PBMCs both alphabetaTCR(+)CD3(+)CD56(-) and alphaTCR(+)CD3(+)CD56(+) (NK-T) CTLs that lysed ACE-sensitized T2 cells in an HLA-A2-restricted manner. The same CTL lines also recognized T2 cells pulsed with HER-2/neu-derived CTL peptide epitopes, a HER-2/neu-transfected HLA-A2(+) cell line and autologous tumor cells. alphaTCR(+)CD3(+)CD56(+) CTL lines also exhibited NK-like cytotoxicity against autologous tumor cells. CTL clones were isolated from alphaTCR(+)CD3(+)CD56(+) bulk cultures displaying both MHC- and non-MHC-restricted cytotoxicity, thus confirming the dual cytolytic function of such cells. Our data demonstrate that ACE from metastatic ovarian tumors can be used as multiepitope vaccines for generating in vitro, besides classical CTLs, NK-T cells exerting efficient MHC- and non-MHC-restricted cytotoxicity against autologous tumor targets. Such NK-T cells expressing dual cytotoxic activity may prove advantageous in cancer immunotherapy.

Adenocarcinoma↗
PubMed1992

Growth-associated protein GAP-43 and nerve cell adhesion molecule in sensory nerves of cornea.

We used dual-wavelength fluorescence microscopy and monoclonal antibodies to growth-associated protein (GAP-43) and nerve cell adhesion molecule (N-CAM) to identify these proteins in nerve fibers of normal rat and rabbit corneas. Overlapping immunoreactivity of GAP-43 and N-CAM was evident along nerve fibers of rabbit corneal sections, suggesting that GAP-43 is constitutively expressed in these sensory nerves. The immune reaction of monoclonal antibody to GAP-43 and [125I]protein A was used to quantitate relative amounts of GAP-43 in the normal cornea and in a cornea subjected to a de-epithelializing wound. Collectively these findings imply that GAP-43 is axoplasmically transported from cells in the trigeminal (or superior cervical) ganglion to the cornea. Moreover, these data indicate that GAP-43 appears to be involved in the remodeling of corneal nerves that is necessary for normal innervation.

Animals↗
PubMed2004

Youth violence perpetration: what protects? What predicts? Findings from the National Longitudinal Study of Adolescent Health.

PURPOSE: To identify individual, family and community-level risk and protective factors for violence perpetration in a national sample of adolescents. METHODS: Analysis of two waves of data from the National Longitudinal Study of Adolescent Health. The key outcome variable was Time 2 violence involvement, approximately 1 year after initial data collection, measured by a validated scale of violence perpetration RESULTS: Controlling for demographic covariates in multivariate regression models, key Time 1 protective factors against Time 2 violence perpetration included measures related to parental expectations, connectedness with parents and other adults, and school, higher grade point average and religiosity. Significant predictive risk factors included a history of violence involvement and violence victimization, weapon carrying, school problems, substance use, health problems, and friend suicide. Probability profiles then assessed the ability of protective factors to offset known risk factors for violence. For both girls and boys there were substantial reductions in the percentage of youth involved in violence in the presence of protective factors, even with significant risk factors present. CONCLUSIONS: Findings support the utility of a dual strategy of reducing risk factors while enhancing protective factors in the lives of adolescents.

Adolescent↗