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Biomedical subjects

B Short

Publications and source records attributed to B Short.

At least 19 recordsLinked to original sources
PubMed2006

Staphylococcal chromosome cassette evolution in Staphylococcus aureus inferred from ccr gene complex sequence typing analysis.

Staphylococcal chromosome cassette mec (SCCmec) elements within major lineages of healthcare- and community-associated methicillin-resistant Staphylococcus aureus (MRSA) clones were characterised using intra-SCCmec multilocus sequencing. A strong correlation was observed between sequence- and PCR-based typing methods (p <0.001). However, phylogenetic analysis of the SCCmec locus using concatenated sequences evidenced few recombination events. Sequence type (ST)-SCCmec1 was found in SCCmec elements types I and IV, suggesting the evolution of an SCCmecI element into an SCCmecIV element. This coincided with the spread of the clone harbouring this SCCmec element into the community. No correlation was observed between ST-SCCmec lineage and MRSA lineage, confirming multiple acquisitions of SCCmec by S. aureus. This was exemplified by the SCCmecIV ST-SCCmec10 element, which was detected in all of the clonal complexes examined, including healthcare- and community-associated MRSA. The acquisition of this SCCmec element was five- to ten-fold more common than that of others. Models of MRSA clone evolution suggest that this SCCmec was first found in the paediatric clone.

DNA Primers↗
PubMed2004

Bimatoprost: a novel antiglaucoma agent.

The aim of glaucoma therapy is to preserve vision by reducing intraocular pressure (IOP). Following recent National Eye Institute sponsored studies, it is becoming increasingly apparent that every mmHg of extra IOP lowering counts. Bimatoprost is the newest and most effective addition to the physician's armamentarium of ocular hypotensive drugs. Direct clinical comparisons have demonstrated that it is more efficacious than the prostaglandin (PG) FP receptor agonist prodrugs, latanoprost and travoprost, as well as a beta-adrenoceptor antagonist, timolol, alone or in fixed combination with the carbonic anhydrase inhibitor, dorzolamide. Moreover, patients that are refractory to latanoprost therapy may be successfully treated with bimatoprost. Such evidence provides support, at the clinical level, for the contention that bimatoprost is pharmacologically distinct from PG FP receptor agonist prodrugs. Bimatoprost is a structural analog of PGF2alpha-ethanolamide (prostamide F2alpha), which is formed from the endocannabinoid anandamide by a biosynthetic pathway involving cyclooxygenase-2 (COX-2). Their pharmacology is remarkably similar, such that bimatoprost may be regarded as a prostamide mimetic. The target receptor for bimatoprost and the prostamides appears unique and unrelated to PG- and endocannabinoid-sensitive receptors. Extensive ocular distribution/metabolism studies in non-human primates demonstrate that bimatoprost is not a prodrug, it remains essentially intact. Its profound ocular hypotensive effects may, therefore, be attributed to its prostamide-mimetic properties.

Amides↗
PubMed2001

A GRASP55-rab2 effector complex linking Golgi structure to membrane traffic.

Membrane traffic between the endoplasmic reticulum (ER) and Golgi apparatus and through the Golgi apparatus is a highly regulated process controlled by members of the rab GTPase family. The GTP form of rab1 regulates ER to Golgi transport by interaction with the vesicle tethering factor p115 and the cis-Golgi matrix protein GM130, also part of a complex with GRASP65 important for the organization of cis-Golgi cisternae. Here, we find that a novel coiled-coil protein golgin-45 interacts with the medial-Golgi matrix protein GRASP55 and the GTP form of rab2 but not other Golgi rab proteins. Depletion of golgin-45 disrupts the Golgi apparatus and causes a block in secretory protein transport. These results demonstrate that GRASP55 and golgin-45 form a rab2 effector complex on medial-Golgi essential for normal protein transport and Golgi structure.

Animals↗
PubMed2000

Alcohol home delivery services: a source of alcohol for underage drinkers.

OBJECTIVE: This study describes the use of alcohol home delivery services by underage drinkers, and characteristics of grocery and liquor stores that deliver alcohol. The availability of alcohol home delivery services across the United States is also described. METHOD: Individuals surveyed were from 15 small- and medium-sized midwestern communities. Of all enrolled 12th graders, 83.5% (N = 4,487) responded, and of a randomly selected cohort of 18- to 20-year-olds, 93.9% (N = 1,721) responded. All grocery stores that sold alcohol and liquor stores in the corresponding communities were invited to participate in the study and 124 (92.5%) of those businesses completed surveys regarding outlet characteristics and practices. Data for the surveys were based on a nested cross-sectional design with individual respondents nested within the 15 communities. RESULTS: Purchases of delivered alcohol were made by 10% of 12th graders and 7.3% of 18- to 20-year-olds within the past year; 20.2% of outlets delivered alcohol. Using bivariate analyses, purchasing delivered alcohol was associated with male gender, high-risk drinking (drinking five or more drinks on an occasion), more recent and more frequent drinking. Providing delivery services was more common among outlets selling keg beer and/or single servings. Multivariate analyses revealed positive associations between purchasing delivered alcohol and male gender for the 12th graders, and high risk and more recent drinking for both the 12th graders and 18- to 20-year-olds. For outlets, selling keg beer was positively associated with providing delivery services. A separate survey indicated that home delivery services appear to be available in many areas of the country. CONCLUSIONS: Home delivery is a previously unidentified source of alcohol for underage drinkers that could be curtailed with effective alcohol policies.

Adolescent↗
PubMed1998

Effects of endothelin receptor antagonism and angiotensin-converting enzyme inhibition on cardiac and renal remodeling in the rat.

The effects of a nonpeptide, orally active mixed endothelin (ET) ETA/ETB receptor antagonist, SB 217242, and an angiotensin-converting enzyme (ACE) inhibitor, ramipril, were evaluated after inter-renal aortic banding in the rat. Separate sham, vehicle, and treatment groups were compared in each study. In vehicle-treated animals in the ramipril group, aortic banding for 4 weeks produced significant cardiac hypertrophy (247 +/- 5 mg/100 g bw vs. 305 +/- 11 mg/100 g bw; p < 0.001), right (upstream) renal hypertrophy (380 +/- 6 mg/100 g bw vs. 559 +/- 28 mg/100 g bw; p < 0.001), and significant left (downstream) renal atrophy (405 +/- 4 mg/100 g bw vs. 192 +/- 25 mg/100 g bw; p < 0.001). Continuous ramipril treatment (1 mg/kg p.o. once daily), begun 3 days before aortic banding, inhibited cardiac hypertrophy (305 +/- 11 mg/100 g bw vs. 266 +/- 7 mg/100 g bw; p < 0.05) but did not alter renal hypertrophy or atrophy. In a similarly designed study, SB 217242 (30 mg/kg p.o. b.i.d.) had no effect on the development of cardiac hypertrophy (298 +/- 7 mg/100 g bw vs. 310 +/- 12 mg/100 g bw) or renal hypertrophy (561 +/- 15 mg/100 g bw vs. 575 +/- 19 mg/100 g bw), but abolished the development of renal atrophy (158 +/- 16 mg/100 g bw vs. 395 +/- 19 mg/100 g bw; p < 0.001). [125I]ET-1 radioligand binding experiments indicated that the density of both ETA and ETB receptors was increased dramatically (three- to fourfold) in the atrophic kidney cortex compared to sham or hypertrophic kidneys. In situ hybridization studies indicate an upregulation of ETB receptor mRNA in the glomeruli of atrophic kidneys within 5 days of aortic banding. In conclusion, an angiotensin-dependent mechanism may mediate cardiac hypertrophy associated with aortic banding, whereas ET-dependent mechanisms may mediate an atrophic response in the hypoperfused kidney, perhaps through an interaction with upregulated ETA and/or ETB receptors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Management of postmenopausal osteoporosis for primary care.

OBJECTIVE: The shift in health care delivery from a subspecialty to primary care system has transferred the responsibility of preventing osteoporotic fractures from specialists in metabolic bone disease to the web of physicians--family practitioners, general internists, pediatricians, and gynecologists--who provide the bulk of primary care. The challenge for this group of physicians is to decrease the rising prevalence of osteoporotic hip and vertebral fractures while operating within the cost parameters. It is the goal of this brief summary to provide primary practitioners with focused guidelines for the management of postmenopausal osteoporosis based on new and exciting developments. Prevention and treatment will change rapidly over the next decade and these advances will require changes in these recommendations. DESIGN: We identified patients at risk for osteoporosis and provided indications for bone mass measurement, criteria for diagnosis of osteoporosis, therapeutic interventions, and biochemical markers of the disease. RESULTS: Prevention and treatment are discussed, including hormone replacement therapy and use of calcitonin, sodium fluoride, bisphosphonates, and serum estrogen receptor modulators. CONCLUSIONS: Postmenopausal osteoporosis should no longer be an accepted process of aging. It is both preventable and treatable. Primary care physicians must proactively prevent and treat osteoporosis in their daily practice, and combination therapies are suggested.

Absorptiometry, Photon↗
PubMed1997

Alcohol-related problems among black, Hispanic and white men: the contribution of neighborhood poverty.

OBJECTIVE: We examined the cross-sectional relationships between race/ethnicity, neighborhood poverty and alcohol-related problems among black, Hispanic and white male drinkers. Test hypotheses were that black and Hispanic men living in more impoverished neighborhoods would report increased numbers of alcohol-related problems than comparable white men. METHOD: Study hypotheses were tested in a sample of 744 black, Hispanic and white men participating in the 1992 National Alcohol Follow-up Survey. Study hypotheses were analyzed using generalized linear model regression analysis. RESULTS: Neighborhood poverty had a greater effect on alcohol-related problems in black than in white men, partially supporting our hypothesis. Black men living in more impoverished neighborhoods reported greater numbers of alcohol-related problems than comparable white men; there were no race differences among more affluent men. Neighborhood poverty had little effect on alcohol-related problems in Hispanic men. CONCLUSIONS: Findings suggest that, giving unfavorable economic conditions, black men will report greater numbers of alcohol-related problems than comparable white men.

Adult↗
PubMed1997

Thrombin increases clusterin mRNA in glomerular epithelial and mesangial cells.

Clusterin, a multifunctional protein with complement blocking activity, and fibrin, a product of thrombin's enzymatic activity, are present in the kidney during acute and chronic renal failure. The role of thrombin in regulating clusterin mRNA in the kidney is not known. The effect of thrombin on clusterin mRNA expression was examined in rat glomerular mesangial and glomerular epithelial cells, and cultured human renal proximal tubular epithelial cells by northern blot. Thrombin (10(-8) M) increased clusterin mRNA levels two- to fourfold in glomerular mesangial, glomerular epithelial, and proximal tubule epithelial cells. This was a specific effect of thrombin receptor activation because peptides corresponding to the tethered ligand of the thrombin receptor were also able to increase clusterin mRNA levels. Epidermal growth factor, insulin-like growth factor-1, and transforming growth factor-beta 1 had little or no effect on clusterin mRNA levels. The protein kinase C inhibitor RO-32-0432 (1 microM) inhibited the thrombin-induced increase in clusterin mRNA, suggesting that thrombin receptor activation may regulate renal clusterin mRNA levels through protein kinase C.

Animals↗
PubMed1997

Environmental predictors of drinking and drinking-related problems in young adults.

We examined relationships among drinking norms, peer alcohol use, alcohol availability, drinking location, alcohol consumption, and drinking-related problems among young adult drinkers. The specific objectives of our study were to assess the relative contribution of normative and physical environmental factors to drinking and drinking consequences. Subjects were 3,095 young adults, aged eighteen to twenty years old who participated in the Communities Mobilizing for Change on Alcohol Project baseline survey. Alcohol consumption (i.e., number of drinks on the last occasion) and drinking consequences served as dependent variables. Multiple linear regression was used to identify predictors of alcohol consumption, and logistic regression was employed to identify predictors of drinking consequences. Drinking norms and peer alcohol use were positively related to alcohol consumption and to drinking consequences. Drinking in a public setting was positively related to alcohol consumption, but not to drinking-related problems. Findings suggest that policies and programs that alter the normative and physical environment surrounding drinking may reduce alcohol consumption and subsequent problems in young adults.

Adolescent↗
PubMed1997

Relationships among alcohol availability, drinking location, alcohol consumption, and drinking problems in adolescents.

We examined relationships among perceived alcohol availability, drinking location, alcohol consumption, and drinking problems. Subjects were 3,372 adolescent drinkers, ages 16-18, who participated in the Communities Mobilizing for Change on Alcohol Project baseline survey. Mixed-model regression was employed to identify predictors of alcohol consumption and drinking consequences. Perceived alcohol availability was significantly associated with higher levels of alcohol consumption for males. Drinking in a public location with higher levels of alcohol consumption for females. Results underscore the importance of youth alcohol assessibility.

Adolescent↗
PubMed1996

Intraclass correlation among measures related to alcohol use by school aged adolescents: estimates, correlates and applications in intervention studies.

School-based alcohol use prevention studies frequently employ designs in which schools are assigned to treatment conditions while observations are made on individuals. The nesting of schools within treatment conditions requires that the treatment effect be assessed against the between-school variance; unfortunately, that variance is usually larger than for randomly constituted groups and its precision is usually less than that for the within-school variance. These factors often combine to reduce power substantially. To address these problems, investigators need good estimates for the intraclass correlation which together with the number of observations per school determines the magnitude of the extra variation in the nested design. This article presents estimates of school-level intraclass correlation for measures related to alcohol use among ninth and twelfth grade students and discusses their use in planning new studies and analyzing previous or current studies.

Adolescent↗
PubMed1995

Intraclass correlation among measures related to alcohol use by young adults: estimates, correlates and applications in intervention studies.

OBJECTIVE: Alcohol intervention studies that allocate intact social groups to study conditions require adjustment to the usual analytic methods to account for the positive intraclass correlation that exists in such groups. This article presents intraclass correlations for measures related to alcohol use among young adults and discusses the use of those estimates to plan new studies. METHOD: Young adults aged 18-20 were selected at random from driver's license lists in each of the 15 communities participating in the Communities Mobilizing for Change on Alcohol project. Respondents were surveyed by telephone to assess their drinking habits and other factors related to alcohol use. Community-level intraclass correlations were computed for those measures, both prior to and after adjustment for person- and community-level covariates. RESULTS: The community-level intraclass correlations tend to be small, with larger values for belief and attitude items than for self-reported behaviors. Even so, correlations of this magnitude can have important deleterious effects on the power to detect important treatment effects in an otherwise well-designed and well-executed study. Adjustment for person-level covariates often reduced those correlations, and adjustment for community-level covariates often reduced them substantially. CONCLUSIONS: There is measurable variation in measures related to alcohol use among young adults that is attributable to their community of residence. With adjustment for selected person- and community-level covariates, the magnitude of these correlations can be sharply reduced allowing the investigator to plan a more efficient community trial.

Adolescent↗
PubMed1994

Distinguishable groups of musculoskeletal low back pain patients and asymptomatic control subjects based on physical measures of the NIOSH Low Back Atlas.

STUDY DESIGN: The authors performed an empirical prospective study of 115 patients referred to physical therapy for low back pain and 112 control subjects of similar age and gender. OBJECTIVES: The authors defined and compared subgroups based on physical tests and described demographic and psychosocial characteristics by group. SUMMARY OF BACKGROUND DATA: Prospective studies of intervention for persons with low back pain are limited by inability to randomize subjects into distinguishable groups. Previous attempts have not been empirical and have not focused on musculoskeletal LBP. METHODS: Ten physical therapists administered 52 tests and 6 questionnaires to subjects in seven different clinics. Data were subjected to reliability and cluster and comparative analyses. RESULTS: Tests were reliable. Groups were distinguished by measures of symmetry, flexibility, strength, and dynamic mobility. CONCLUSION: Distinguishable groups can be determined; decreased trunk mobility characterized all groups of patients and imbalances in muscle length, strength, and symmetry described specific groups of subjects with and without low back pain.

Cluster Analysis↗
PubMed1994

Selective inhibition of 5-lipoxygenase attenuates glomerulonephritis in the rat.

Three hours following injection of anti-GBM (glomerular basement membrane) antibody (10 mg/kg, i.v.) into rats, glomerular production of LTB4 was significantly increased as compared to untreated rats (497 +/- 26 vs. 244 +/- 18 pg of LTB4/mg protein). Twenty-four hours following administration of anti-GBM antibody, renal function (blood urea nitrogen, BUN; plasma creatinine, PCr; creatinine clearance, CCr; fractional excretion of sodium, FENa; fractional excretion of urea, FEUrea) was determined to be impaired proportionally to the amount of injected antibody (5 to 30 mg/kg, i.v.). In a second series of experiments, a selective 5-lipoxygenase (5-LO) inhibitor, SK&F 107649, was used to investigate the involvement of 5-LO products in the pathophysiology of anti-GBM antibody-induced glomerulonephritis. In preliminary experiments. SK&F 107649 (50 to 200 mg/kg, p.o.) inhibited ionophore (A23187)-stimulated whole blood leukotriene (LT) B4 production in a dose-dependent fashion (P < 0.05 at doses > or = 100 mg/kg). The anti-GBM antibody-mediated decrease in glomerular filtration rate (GFR) and increase in BUN and PCr were dose-dependently attenuated by SK&F 107649 (50 to 200 mg/kg, p.o. BID). These data confirm that glomerular LTB4 production is stimulated in anti-GBM antibody-induced glomerulonephritis, and demonstrate that inhibition of 5-LO by SK&F 107649 normalizes BUN and PCr and attenuate the decrease in GFR following anti-GBM antibody treatment. These results provide additional evidence for a role of 5-LO products in immune-mediated renal disease, and suggest that pharmacologic inhibition of 5-LO may be of therapeutic value.

Animals↗
PubMed1994

High risk sexual behavior and alcohol consumption among bar-going gay men.

OBJECTIVES: To determine whether alcohol use prior to sexual behavior influenced the occurrence of unprotected anal intercourse among bar-going gay men. METHODS: Anonymous AIDS behavioral risk surveys were administered to men entering gay bars in 16 cities on three nights in February 1993 in six states in the United States. RESULTS: Of the 1519 men who completed the survey, 85% were current alcohol drinkers. Men who had unprotected anal intercourse after consuming alcohol drank more and reported more incidents of unprotected anal intercourse than men who had unprotected anal intercourse but not after drinking. Overall, unprotected anal intercourse occurred less frequently after alcohol consumption than without prior consumption. CONCLUSIONS: This study found that heavy alcohol use and frequent high-risk sexual behavior occurred among the same individuals. However, we found no evidence for a causal link between alcohol use and unprotected sexual behavior in this sample of bar-going gay men.

Adult↗