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PubMed2006

Alcohol outlets, gonorrhea, and the Los Angeles civil unrest: a longitudinal analysis.

This study tests the effect of neighborhood changes on gonorrhea rates. Prior studies that indicate gonorrhea rates are associated with alcohol outlet density and neighborhood deterioration have been cross-sectional and cannot establish causality. After the 1992 Civil Unrest in Los Angeles, 270 alcohol outlets surrendered their licenses due to arson and vandalism thus providing a natural experiment. We geocoded all reported gonorrhea cases from 1988 to 1996 in LA County, all annually licensed alcohol outlets, and all properties damaged as a result of the civil unrest. We ran individual growth models to examine the independent effects of changes in alcohol outlets and damaged buildings on gonorrhea. The individual growth model explained over 90% of the residual variance in census tract gonorrhea rates. After the civil unrest, a unit decrease in the number of alcohol outlets per mile of roadway was associated with 21 fewer gonorrhea cases per 100,000 (p<.01) in tracts affected by the Unrest compared to those not affected. Neighborhood alcohol outlets appear to be significantly associated with changes in gonorrhea rates. The findings suggest that efforts to control sexually transmitted diseases, including gonorrhea and HIV, should address contextual factors that facilitate high-risk behaviors and disease transmission.

Adolescent↗

PubMed2006

Lethal giant larvae take on a life of their own.

Cell polarization requires the segregation of the plasma membrane into domains of distinct protein composition. The Lethal giant larvae (Lgl) protein of Drosophila, initially identified as a tumor suppressor, establishes such domains by localizing specific proteins to specific regions of the plasma membrane. However, how it does this remains puzzling and controversial. Recent studies of the yeast orthologs show a molecular pathway through which Lgl is activated locally to promote the targeted fusion of vesicles with the plasma membrane. Here, we reconcile these data with conflicting findings on the mechanism of Lgl in animals and consider if a similar model explains its role in epithelial polarity and asymmetric cell division.

Animals↗

PubMed2004

Analysis of PSP toxins in Norwegian mussels by a post-column derivatization HPLC method.

The aim of this study was to investigate the agreement between the AOAC mouse bioassay and an HPLC method for determining Paralytic Shellfish Poisoning (PSP) toxicity in blue mussels from the Norwegian coast. The AOAC mouse bioassay has traditionally been used for determining the toxin levels. Recently, an HPLC method for determining PSP toxins has been implemented and run in parallel with the bioassay. Four hundred mussel extracts from the last six years were analysed with both methods. A highly significant linear correlation between the methods was achieved (r = 0.84). However, the relation between the two methods was best described by a second-degree polynom. Totally, this model explained 87% of the variation in the HPLC method. By agreement analysis, it was possible to establish cut-off levels for the HPLC method related to the AOAC mouse bioassay with kappa values >0.80 for toxicity levels below 500 MU/100 g. The HPLC method could substitute the mouse bioassay in determining PSP toxicity in Norwegian mussels. Additionally, about 70 mussel samples were also analysed by the MIST Alert trade mark test kit. The kit did not give any false negative results compared with the regulatory limit, but 30% of the samples below the cut point were also determined as positive.

Animals↗

PubMed2005

Incidence of oral candidiasis and oral hairy leukoplakia in HIV-infected adults in North Carolina.

OBJECTIVES: To establish incidence rates and risk factors for HIV-associated oral candidiasis (OC), oral hairy leukoplakia (OHL), and any HIV-associated oral diseases (HIV-OD). DESIGN: This prospective, cumulative case-control study followed 283 initially oral disease-free HIV-1-infected men and women for 2 years. Incidence rate ratios (IRR) and incidence proportions for OC, OHL, and HIV-OD were estimated. Multivariable analyses using Poisson regression determined the most parsimonious best-fitting model explaining the outcomes. RESULTS: Incidence rate (per 1000 person-months) was 9.3 for OC, 6.8 for OHL, and 13.5 for HIV-OD. Incidence of OC was associated with low CD4 count (adjusted IRR = 3.0 (95% CI = 1.7, 5.1)), smoking (IRR = 1.9 (1.0, 3.8)) and combination antiretroviral therapy (IRR = 0.3 (0.1, 0.8)). Incidence of OHL was associated with low CD4 count, conditional upon smoking status. Conclusions Low CD4 count and smoking are important risk factors for HIV-associated OC and OHL. Antiretroviral medications are protective for OC but not for OHL.

AIDS-Related Opportunistic Infections↗

PubMed2005

15-zinc finger protein Bloody Fingers is required for zebrafish morphogenetic movements during neurulation.

A novel zebrafish gene bloody fingers (blf) encoding a 478 amino acid protein containing fifteen C(2)H(2) type zinc fingers was identified by expression screening. As determined by in situ hybridization, blf RNA displays strong ubiquitous early zygotic expression, while during late gastrulation and early somitogenesis, blf expression becomes transiently restricted to the posterior dorsal and lateral mesoderm. During later somitogenesis, blf expression appears only in hematopoietic cells. It is completely eliminated in cloche, moonshine but not in vlad tepes (gata1) mutant embryos. Morpholino (MO) knockdown of the Blf protein results in the defects of morphogenetic movements. Blf-MO-injected embryos (morphants) display shortened and widened axial tissues due to defective convergent extension. Unlike other convergent extension mutants, blf morphants display a split neural tube, resulting in a phenotype similar to the human open neural tube defect spina bifida. In addition, dorsal ectodermal cells delaminate in blf morphants during late somitogenesis. We propose a model explaining the role of blf in convergent extension and neurulation. We conclude that blf plays an important role in regulating morphogenetic movements during gastrulation and neurulation while its role in hematopoiesis may be redundant.

Amino Acid Sequence↗

PubMed1996

Predictors of physical activity in patients with chronic heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.

To identify predictors of physical activity levels in patients with chronic heart failure, 43 patients, aged 33 to 91 years, who had well-compensated heart failure were asked to perform a symptom-limited exercise treadmill test and to complete activity logs for 2 consecutive days while wearing an ambulatory heart rate activity monitor. Activity logs included information on the type of activity, duration, rating of perceived exertion, symptoms experienced, and the intensity of symptoms. Subjects also completed the Duke Activity Status Index, a brief self-administered questionnaire that assesses physical functioning, and a self-efficacy for general activity questionnaire. Simultaneous multiple regression analysis was used to predict physical activity levels from a model that included: personal variables of physical fitness (peak oxygen consumption); knowledge, attitudes, and beliefs including self-efficacy for general activity, and rating of perceived exertion during daily activity; and environmental factors such as social support (marital status). The overall model explained 38% of the variance (p < 0.001). Self-efficacy (p = 0.015) was the strongest predictor of physical activity in this group. From this initial descriptive study, we conclude that self-efficacy is a better predictor of performance of physical activity than measures of physical fitness or rating of perceived exertion during activity. Additional studies are needed to examine other behavioral and physiologic mediators as well as behavioral strategies that may be used to increase participation in physical activity programs. Particularly promising are strategies to enhance self-efficacy for exercise.

Adult↗

PubMed1997

Effects of bifunctional netropsin-related minor groove-binding ligands on mammalian type I DNA topoisomerase.

We investigated the effects of compounds with two covalently linked netropsin moieties (bis-netropsin) on the function of mammalian type I DNA topoisomerase (topo I) in vitro. We initiated these studies because earlier studies had shown that certain bis-netropsins possess a several-fold higher antitumor and antiviral activity than netropsin. We confirmed that the parent compound netropsin, but not its bifunctional derivatives, induce supercoils in closed DNA. We determined that bis-netropsins inhibit the binding of topo I to DNA more efficiently than netropsin and that bis-netropsins but not netropsin induce specific DNA strand cleavage in the presence of topo I. We discuss a model explaining the different effects of netropsin and bis-netropsins on topo I.

Antineoplastic Agents↗

PubMed1982

Solvation properties of natural and synthetic ionophores. I. Stoichiometry of complexes with alkali and alkaline earth cations in aprotic organic solvents.

Ion-solvent interactions play a very important role in the studies of stoichiometry, structure, and stability of complexes of cations with natural and synthetic ionophores. These compounds are extremely useful in study of the interaction of neutral salts with macromolecules and the mechanism of cation transport across biological membranes. Knowledge of the ionophore solvation properties enables one to choose a suitable solvent for complexation studies and to obtain detailed information on the solvent effect. We would like to present in this paper a very simple method of estimating the solvation properties of ionophores. We treat the ligand as an assembly of individual noninteracting binding sites. The solvation properties of solvents can be used to represent the solvation sites in natural and synthetic ligands. The solvation properties are represented by the Gutmann donor number (DN) of the model solvent. We can define the solvation ability of a ligand binding site be "donor number of binding site" (DN binding site), which in turn can be represented by the DN of the appropriate model solvent. The average DN of the ligand (DN average) is defined as [xi ni-1 (DN binding site)i]/n, where n is the number of the ligand binding sites. Comparison of the DN average with the DN solvent, together with the knowledge of the composition of the system, characterizes remarkably well the solvation properties of the ligand. This model explains (a) the stoichiometry of many alkali and alkaline earth cation complexes with natural and synthetic ligands in aprotic organic solvents, (b) the transport of alkali and alkaline earth cations across lipid bilayers, and (c) how polypeptides and proteins interact with neutral salts in solutions.

Cations↗

PubMed2003

Differential apolipoprotein(a) isoform expression in heterozygosity is an independent contributor to lipoprotein(a) levels variability.

BACKGROUND AND METHODS: Lipoprotein(a) [Lp(a)] levels represent an independent risk factor for cardio- and cerebrovascular diseases. Since lipoprotein(a) levels show a wide variability even in subjects with similar apolipoprotein(a) isoforms, we investigated the contribution of apolipoprotein(a) heterozygosity to lipoprotein(a) variance. Lipoprotein(a) levels, apolipoprotein(a) isoforms identification and expression, and the correlation with other lipo-apolipoprotein parameters have been investigated in 628 subjects >18 years of age. RESULTS: In our study, 246 subjects were found heterozygous for apolipoprotein(a) isoforms. Lipoprotein(a) levels were higher in females. About 40% of the subjects expressed the larger isoform more intensely than the dominant isoform. Lipoprotein(a) was correlated with apolipoprotein(a) dominant isoform size, HDL-cholesterol and smaller apolipoprotein(a) isoform expression rate. Lipoprotein(a) was independently correlated with the smaller apolipoprotein(a) isoform, with its expression rate and with LDL-cholesterol. The inclusion of the smaller apolipoprotein(a) expression rate in a multiple regression model explained at least an additional 4% of the lipoprotein(a) variance after correction for apolipoprotein(a) size. CONCLUSIONS: The smaller isoforms are not always effectively dominant in heterozygosis since 40% of the subjects expressed more the larger isoform. The individual variability of apolipoprotein(a) isoform expression in heterozygosis could explain part of the lipoprotein(a) levels variability.

Adult↗

PubMed2002

A bird's eye view: biological categorization and reasoning within and across cultures.

Many psychological studies of categorization and reasoning use undergraduates to make claims about human conceptualization. Generalizability of findings to other populations is often assumed but rarely tested. Even when comparative studies are conducted, it may be challenging to interpret differences. As a partial remedy, in the present studies we adopt a 'triangulation strategy' to evaluate the ways expertise and culturally different belief systems can lead to different ways of conceptualizing the biological world. We use three groups (US bird experts, US undergraduates, and ordinary Itza' Maya) and two sets of birds (North American and Central American). Categorization tasks show considerable similarity among the three groups' taxonomic sorts, but also systematic differences. Notably, US expert categorization is more similar to Itza' than to US novice categorization. The differences are magnified on inductive reasoning tasks where only undergraduates show patterns of judgment that are largely consistent with current models of category-based taxonomic inference. The Maya commonly employ causal and ecological reasoning rather than taxonomic reasoning. Experts use a mixture of strategies (including causal and ecological reasoning), only some of which current models explain. US and Itza' informants differed markedly when reasoning about passerines (songbirds), reflecting the somewhat different role that songbirds play in the two cultures. The results call into question the importance of similarity-based notions of typicality and central tendency in natural categorization and reasoning. These findings also show that relative expertise leads to a convergence of thought that transcends cultural boundaries and shared experiences.

Adult↗

PubMed1996

Lipopolysaccharide-binding protein mediates CD14-independent intercalation of lipopolysaccharide into phospholipid membranes.

Lipopolysaccharides (LPS, endotoxin) stimulate mononuclear cells to release cytokines which initiate endotoxic effects. Interaction of LPS at low concentrations with target cells is CD14-dependent whereas at high LPS concentrations it is CD14-independent. Here, we demonstrate by resonance energy transfer (RET) technique that nonspecific, CD14-independent intercalation of LPS into membrane systems can be mediated by lipopolysaccharide-binding protein (LBP). It is proposed that in this pathway, LBP breaks down LPS aggregates, transports the smaller units to and inserts them into the phospholipid cell matrix. We furthermore show that LBP also mediates the intercalation of other negatively charged amphiphilic molecules. We propose a model explaining CD14-independent cell activation at high endotoxin concentrations.

Acute-Phase Proteins↗

PubMed2001

The relation of oxidized LDL autoantibodies and long-term hormone replacement therapy to ultrasonographically assessed atherosclerotic plaque quantity and severity in postmenopausal women.

BACKGROUND: In epidemiologic studies, the incidence of atherosclerosis rises soon after menopause in women, and hormone replacement therapy (HRT) has proved to be useful in preventing onset of clinical manifestations of the disease. However, it is not known how HRT affects sonographically determined atherosclerotic severity (AS) and number of atherosclerotic plaques (NAP) in large arteries. Furthermore, it is not clear how HRT affects oxidation of low density lipoproteins (LDL), which obviously has an important role in the pathogenesis of atherosclerosis. OBJECTIVES: The purpose of the study was to determine whether HRT has a beneficial effect on sonographically determined AS and NAP in large arteries of 101 postmenopausal women compared to 40 controls without HRT. We also studied the interaction of HRT and antibodies against oxidized LDL on AS and NAP progression. RESULTS: Estradiol valerate alone, combined estradiol valerate-levonorgestrel and combined estradiol valerate-medroxyprogesterone acetate therapy are each associated with lower NAP and AS as compared to controls without HRT. In a multiple regression model explaining NAP in the whole study population, the strongest predictors were HRT (P=0.0006) and copper-oxidized LDL cholesterol autoantibodies (P=0.0491). DISCUSSION: Our findings indicate that postmenopausal HRT is associated with a lower total number of atherosclerotic plaques and less severe atherosclerotic lesions, as compared to controls without HRT, and that this outcome may be associated with the effect of HRT on LDL cholesterol oxidation.

Aged↗

PubMed1992

Treatment of children with homozygous familial hypercholesterolemia: safety and efficacy of low-density lipoprotein apheresis.

We evaluated the safety and efficacy of dextran sulfate low-density lipoprotein (LDL) apheresis in the treatment of three children (aged 6, 7, and 10 years) with severe familial homozygous hypercholesterolemia and undetectable LDL receptor activity. A total of 35 double plasma volume procedures were performed. The ranges of the mean decreases of the three patients in plasma lipid concentrations after LDL apheresis (p less than 0.0001) were as follows: total cholesterol, 76% to 79%; LDL-cholesterol, 78% to 81%; very low density lipoprotein cholesterol, 69% to 75%; high-density lipoprotein cholesterol, 27% to 40%; and triglycerides, 34% to 68%. There were statistically significant but clinically and biologically irrelevant changes in hematologic indexes, serum chemistry values, immunoglobulin levels, complement activity, and plasma concentrations of fat-soluble vitamins. Simple correlation analysis of the variables affecting total cholesterol removal showed significant correlation coefficients (r values) for preapheresis total cholesterol values (r = 0.70; p less than 0.01) and preapheresis LDL-cholesterol values (r = 0.61; p less than 0.01). A multiple regression model explained 82% of the variance based on the preapheresis cholesterol concentration, volume of whole blood processed, and the serum albumin concentration. Side effects of the LDL-apheresis treatments were rare and included abdominal cramping and urticaria. Two procedures were aborted because of intravenous access problems in the younger children. This study confirms that LDL apheresis using a dextran sulfate affinity column is efficacious in rapidly lowering total and LDL-cholesterol concentrations. Furthermore, the procedure is safe and well tolerated by children as young as 6 years of age. This treatment may prevent the progression of atherosclerosis in children with homozygous familial hypercholesterolemia and may therefore avert early death.

Blood Component Removal↗

PubMed2002

Perceived safety climate, job demands, and coworker support among union and nonunion injured construction workers.

PROBLEM: This study evaluated injured construction workers' perceptions of workplace safety climate, psychological job demands, decision latitude, and coworker support, and the relationship of these variables to the injury severity sustained by the workers. METHODS: Injury severity was assessed using the Health Assessment Questionnaire (HAQ), which evaluates functional limitations. Worker perceptions of workplace variables were determined by two instruments: (a) the Safety Climate Measure for Construction Sites and (b) the Job Content Questionnaire (JCQ). RESULTS: The overall model explained 23% of the variance in injury severity, with unique contributions provided by union status, the Safety Climate Score, and Psychological Job Demands. A positive significant correlation was found between injury severity and the Safety Climate Scores (r = .183, P = .003), and between the Safety Climate Scores and union status (r = .225, P < .001). DISCUSSION: There were statistically significant differences between union and nonunion workers' responses regarding perceived safety climate on 5 of the 10 safety climate items. Union workers were more likely than nonunion workers to: (a) perceive their supervisors as caring about their safety; (b) be made aware of dangerous work practices; (c) have received safety instructions when hired; (d) have regular job safety meetings; and (e) perceive that taking risks was not a part of their job. However, with regard to the 49-item JCQ, which includes Coworker Support, the responses between union and nonunion workers were very similar, indicating an overall high degree of job satisfaction. However, workers who experienced their workplace as more safe also perceived the level of management (r = -.55, P < .001) and coworker (r = -.31, P < .001) support as being higher. IMPACT ON INDUSTRY: The findings of this study underscore the critical need for construction managers to alert workers to dangerous work practices and conditions more frequently, and express concern and praise workers for safe work in a manner that is culturally acceptable in this industry. Workplace interventions that decrease the incidence and severity of injuries, but that are flexible enough to meet a variety of potentially competing imperatives, such as production deadlines and client demands, need to be identified.

Accidental Falls↗

PubMed2003

Leader RNA binding ability of Chandipura virus P protein is regulated by its phosphorylation status: a possible role in genome transcription-replication switch.

The molecular events associated with the transcriptive and replicative cycle of negative-stranded RNA viruses are still an enigma. We took Chandipura virus, a member of the Rhabdoviridae family, as our model system to demonstrate that Phosphoprotein P, besides Nucleocapsid protein N, also acts as a leader RNA-binding protein in its unphosphorylated form, whereas CKII-mediated phosphorylation totally abrogates its RNA-binding ability. However, interaction between P protein and leader RNA can be distinguished from N-mediated encapsidation of viral sequences. Furthermore, P protein bound to leader chain can successively recruit N protein on RNA while itself being replaced. We also observed that the accumulation of phosphorylation null mutant of P protein in cells results in enhanced genome RNA replication with concurrent increase in the viral yield. All these results led us to propose a model explaining viral transcription-replication switch where Phosphoprotein P acts as a modulator of genome transcription and replication by its ability to bind to the nascent leader RNA in its unphosphorylated form, promoting read-through of the transcription termination signals and initiating nucleocapsid assembly on the nascent RNA chain.

5' Untranslated Regions↗

PubMed2001

Hydrodynamical effects on spatial distribution of enteric bacteria in the Jordan River-Lake Kinneret contact zone.

The aim of this study was to determine under what hydrodynamic conditions the change in the number of enteric bacteria in the water of the River Jordan--Lake Kinneret contact zone was due to sedimentation and under what conditions the change was due to dilution. The data were then utilized to build a conceptual model explaining the distribution of biological pollutants (bacteria) in the river-lake contact zone of a shallow tropical lake. The study uses, as an example, the microbial communities of the River Jordan--Lake Kinneret contact zone. The changes in numbers of three groups of bacteria (fecal coliforms, Escherichia coli and Klebsiella pneumoniae) along the jet flow agree well with changes in the concentration of suspended particulate matter, caused by the sedimentation of particles.

Animals↗

PubMed2002

Contribution of indoor and outdoor environments to PM2.5 personal exposure of children--VESTA study.

Several studies among adult populations showed that an array of outdoor and indoor sources of particles emissions contributed to personal exposures to atmospheric particles, with tobacco smoke playing a prominent role (J. Expo. Anal. Environ. Epidemiol. 6 (1996) 57, Environ. Int. 24 (1998) 405, Arch. Environ. Health 54 (1999) 95). The Vesta study was carried out to assess the role of exposure to traffic emissions in the development of childhood asthma. In this paper, we present data on 68 children aged 8-14 years, living in the metropolitan areas of Paris (n = 30), Grenoble (n = 15) and Toulouse (n = 23), France, who continuously carried, over 48 h, a rucksack that contained an active PM2.5 sampler. Data about home indoor sources were collected by questionnaires. In parallel, daily concentrations of PM10 in ambient air were monitored by local air quality networks. The contribution of indoor and outdoor factors to personal exposures was assessed using multiple linear regression models. Average personal exposure across all children was 23.7 microg/m3 (S.D. = 19.0 microg/m3), with local means ranging from 18.2 to 29.4 microg/m3. The final model explains 36% of the total between-subjects variance, with environmental tobacco smoke contributing for more than a third to this variability; presence of pets at home, proximity of the home to urban traffic emissions, and concomitant PM10 ambient air concentrations were the other main determinants of personal exposure.

Adolescent↗

PubMed2000

Establishing biorientation occurs with precocious separation of the sister kinetochores, but not the arms, in the early spindle of budding yeast.

Sister kinetochores are bioriented toward the spindle poles in higher eukaryotic prometaphase before chromosome segregation. We show that, in budding yeast, the sister kinetochores are separated in the very early spindle, while the sister arms remain associated. Biorientation of the separated kinetochores is achieved already after replication. Mtw1p, a homolog of fission yeast Mis12 required for biorientation, locates at the centromeres in an Ndc10p-dependent manner. Mtw1p and the sequences 1.8 and 3.8 kb from CEN3 and CEN15, respectively, behave like the precociously separated kinetochores, whereas the sequences 23 and 35 kb distant from CEN3 and CEN5 previously used as the centromere markers behave like a part of the arm. Mtw1p and Ndc10p are identically located except for additional spindle localization of Ndc10p. A model explaining small centromeres and early spindle formation in budding yeast is proposed.

Antineoplastic Agents↗