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At least 1,711 records · Page 95Linked to original sources
PubMed1999

Distinct regions of influenza virus PB1 polymerase subunit recognize vRNA and cRNA templates.

The influenza virus RNA polymerase is a heterotrimer comprising the PB1, PB2 and PA subunits. PB1 is the core of the complex and accounts for the polymerase activity. We have studied the interaction of PB1 with model cRNA template by in vitro binding and Northwestern analyses. The binding to model cRNA was specific and showed an apparent Kd of approximately 7x10(-8) M. In contrast to the interaction with vRNA, PB1 was able to bind equally the 5' and 3' arm of the cRNA panhandle. The N-terminal 139 amino acids of PB1 and sequences between positions 267 and 493 proved positive for binding to cRNA, whereas the interaction with vRNA template previously was mapped to the N- and C-terminal regions. Competition experiments using the 5' and 3' arms of either the vRNA or cRNA panhandle indicated that the N-terminal binding site is shared by both templates. The data indicate that the PB1 RNA-binding sites are constituted by: (i) residues located at the N-terminus (probably common for vRNA and cRNA binding) and, either (ii) residues from the central part of PB1 (for cRNA) or (iii) residues from the C-terminal region of PB1 (for vRNA), and suggest that PB1 undergoes a conformational change upon binding to cRNA versus vRNA templates.

Animals↗
PubMed2003

GP referral for physiotherapy to musculoskeletal conditions--a qualitative study.

BACKGROUND: Little is known about the dynamics of GP referral for physiotherapy. Better understanding of this process is important because of the growing number of physiotherapy referrals by GPs. OBJECTIVES: Our aim was to achieve insight into the experiences and views of patients, GPs and physiotherapists in relation to physiotherapy referral for musculoskeletal conditions. METHOD: The study involved qualitative methodology using 22 semi-structured in-depth interviews. The interviews were recorded and transcribed verbatim. The transcripts were coded and analysed using the methods developed in grounded theory. Interviews were undertaken with GPs in primary care, Health Authority and hospital locations. Interviews with physiotherapists and patients were undertaken within community and district hospital locations. RESULTS: Three classifications of referral type were developed by the authors from the data, 'appropriate referral', 'load-sharing referral' and 'dumping referral'. There are descriptions of influences on GP referral behaviour, physiotherapists' response to appropriateness and expectations from the perspective of GPs and physiotherapists. Communication was shown as important in determining appropriate referral, but the quality of communication was variable. GPs' past experience of physiotherapy significantly affected referral. Patients' expectations about physiotherapy were described as variable and sometimes unrealistic. CONCLUSIONS: The selection of appropriate referrals by GPs could be helped by improved communication and better definitions of appropriateness. Closer working between the two professions would result in the better management of problematic patients and prevent wasted resources through avoiding inappropriate referral. Written guidelines appeared to be of less use than direct contact. The concept of expectations appeared relevant to multiple aspects of physiotherapy referral.

Family Practice↗
PubMed2004

Genetics of familial combined hyperlipidemia and risk of coronary heart disease.

Coronary heart disease is the leading cause of death in developed countries. This alarming statistic is partly attributable to lifestyle, and partly due to the genetic factors that make humans highly susceptible to atherosclerotic vascular disease. The principal metabolic causes of atherosclerosis include hyperlipidemia, hypertension, obesity, insulin resistance and diabetes mellitus. Here we discuss the aetiology of familial combined hyperlipidemia (FCHL), a highly atherogenic disorder affecting 1-2% of the Western world. Genome-wide linkage studies indicate that more than three genes contribute to the pernicious lipid profile of FCHL, and that these genes reside within the 1q21-23, 11p14.1-q12.1 and 16q22-24.1 chromosomal regions. Other loci include 1p31, 6q16.1-16.3 and 8p23.3-22, but the linkage data for these are not yet persuasive. Combined linkage and association analyses provide compelling evidence for the involvement of two distinct alleles at the APOA1/C3/A4/A5 gene cluster in the transmission of FCHL. An important lesson arising from the study of a complex genetic disorder, such as FCHL, that lacks a consensus on diagnostic criteria, is that an understanding of complex genetic disorders can derive from comparative analyses of genome-wide linkage data generated from conditions that share phenotypic overlap. The identification of potential genetic overlap between FCHL and the Metabolic Syndrome, which is estimated to affect 47 million Americans, promises to deliver new targets for reducing the risk of important conditions such as cardiovascular disease and stroke.

Alleles↗
PubMed2001

Ecologic versus individual-level sources of bias in ecologic estimates of contextual health effects.

A number of authors have attempted to defend ecologic (aggregate) studies by claiming that the goal of those studies is estimation of ecologic (contextual or group-level) effects rather than individual-level effects. Critics of these attempts point out that ecologic effect estimates are inevitably used as estimates of individual effects, despite disclaimers. A more subtle problem is that ecologic variation in the distribution of individual effects can bias ecologic estimates of contextual effects. The conditions leading to this bias are plausible and perhaps even common in studies of ecosocial factors and health outcomes because social context is not randomized across typical analysis units (administrative regions). By definition, ecologic data contain only marginal observations on the joint distribution of individually defined confounders and outcomes, and so identify neither contextual nor individual-level effects. While ecologic studies can still be useful given appropriate caveats, their problems are better addressed by multilevel study designs, which obtain and use individual as well as group-level data. Nonetheless, such studies often share certain special problems with ecologic studies, including problems due to inappropriate aggregation and problems due to temporal changes in covariate distributions.

Bias↗
PubMed2005

Comorbidity in childhood in northern Ghana: magnitude, associated factors, and impact on mortality.

BACKGROUND: It has been observed that in developing countries terminal illness in children under 5 yr of age is frequently characterized by comorbidity. This study seeks to quantify the co-occurrence of illness at the community level and investigates whether this co-occurrence increases the risk of mortality. We develop an appropriate measure of co-occurrence and investigate whether the comorbidity occurs by chance or whether it is due to shared risk factors. METHODS: The data used for the analysis was taken from a study carried out from 1989 to 1991 in northern Ghana on children aged 2-59 months (n = 1879). Coding for diarrhoea, pneumonia, and measles was carried out using the classification system of the WHO/UNICEF strategy for the Integrated Management of Childhood Illness; malaria was confirmed by laboratory analysis. A bivariate probit analysis was conducted to quantify comorbidity. We used an additive regression model, implemented using the Generalized Estimating Equation approach, to examine the impact on mortality. RESULTS: There is evidence of co-occurrence of diarrhoeal diseases and pneumonia, with greater comorbidity with increasing severity of disease. There is no evidence that the co-occurrence of diarrhoea with severe dehydration and severe pneumonia is characterized by a synergistic effect on mortality risk. CONCLUSIONS: Our study has shown that it is possible to have significant co-occurrence of illness at the community level. The bivariate probit procedure was easily adopted and considered appropriate for the analysis of comorbidity. The lack of suitable datasets for a more thorough analysis of comorbidity, and for the evaluation of synergistic effects on mortality, is a major limitation.

Child, Preschool↗
PubMedDate not supplied

Reproduction and recruitment in perennial colonies of the introduced wasp Vespula germanica.

We investigated the genetic structure of perennial colonies of the yellowjacket wasp (Vespula germanica) in its introduced range in Australia and New Zealand. The nuclear genotypes of 712 gynes from 21 colonies, 147 workers from 5 colonies, and 81 males from 4 colonies were assayed at three polymorphic microsatellite loci. The mitochondrial haplotypes of all wasps also were determined for a 450-bp region of the mtDNA using double-stranded conformational polymorphism (DSCP) analysis. We found that multiple reproductives were needed to explain the genotypes of gynes, workers, and males in 7 of 21, 2 of 5, and 2 of 4 colonies, respectively, and that nestmate relatedness of these three castes equaled 0.42, 0.16, and 0.22, respectively. The mitochondrial data revealed that all individuals shared the same mtDNA haplotype in 20 of the 21 colonies. However, in one colony, gynes and workers displayed multiple mtDNA haplotypes, indicating that nonnestmate recruitment had occurred. Overall the genetic structure within the majority of perennial colonies conformed to expectations based on the biology of V. germanica and kin selection theory for polygyne colonies; multiple reproductives successfully produced offspring and were recruited into their natal nests, thereby maintaining relatively high relatedness between interacting individuals.

Animals↗
PubMed2004

Phylogenetic mapping of intron positions: a case study of translation initiation factor eIF2gamma.

Eukaryotic translation initiation factor 2 (eIF2) is a G protein that delivers the methionyl initiator tRNA to the small ribosomal subunit and releases it upon GTP hydrolysis after the recognition of the initiation codon. eIF2 is composed of three subunits, alpha, beta, and gamma. Subunit gamma shows the strongest conservation, and it confers both tRNA and GTP/GDP binding. Using intron positioning and protein sequence alignment, here we show that eIF2gamma is a suitable phylogenetic marker for eukaryotes. We determined or completed the sequences of 13 arthropod eIF2gamma genes. Analyzing the phylogenetic distribution of 52 different intron positions in 55 distantly related eIF2gamma genes, we identified ancient ones and shared derived introns in our data set. Obviously, intron positioning in eIF2gamma is evolutionarily conserved. However, there were episodes of complete and partial intron losses followed by intron gains. We identified 17 clusters of intron positions based on their distribution. The evolution of these clusters appears to be connected with preferred exon length and can be used to estimate the relative timing of intron gain because nearby precursor introns had to be erased from the gene before the new introns could be inserted. Moreover, we identified a putative case of intron sliding that constitutes a synapomorphic character state supporting monophyly of Coleoptera, Lepidoptera, and Diptera excluding Hymenoptera. We also performed tree reconstructions using the eIF2gamma protein sequences and intron positioning as phylogenetic information. Our results support the monophyly of Viridoplantae, Ascomycota, Homobasidiomyceta, and Apicomplexa.

Amino Acid Sequence↗
PubMed2001

The ARKdb: genome databases for farmed and other animals.

The ARKdb genome databases provide comprehensive public repositories for genome mapping data from farmed species and other animals (http://www.thearkdb.org) providing a resource similar in function to that offered by GDB or MGD for human or mouse genome mapping data, respectively. Because we have attempted to build a generic mapping database, the system has wide utility, particularly for those species for which development of a specific resource would be prohibitive. The ARKdb genome database model has been implemented for 10 species to date. These are pig, chicken, sheep, cattle, horse, deer, tilapia, cat, turkey and salmon. Access to the ARKdb databases is effected via the World Wide Web using the ARKdb browser and Anubis map viewer. The information stored includes details of loci, maps, experimental methods and the source references. Links to other information sources such as PubMed and EMBL/GenBank are provided. Responsibility for data entry and curation is shared amongst scientists active in genome research in the species of interest. Mirror sites in the United States are maintained in addition to the central genome server at Roslin.

Animals↗
PubMed1998

Clusters of Pneumocystis carinii pneumonia: analysis of person-to-person transmission by genotyping.

Genotyping at the internal transcribed spacer (ITS) regions of the nuclear rRNA operon was performed on isolates of P. carinii sp. f. hominis from three clusters of P. carinii pneumonia among eight patients with haematological malignancies and six with HIV infection. Nine different ITS sequence types of P. carinii sp. f. hominis were identified in the samples from the patients with haematological malignancies, suggesting that this cluster of cases of P. carinii pneumonia was unlikely to have resulted from nosocomial transmission. A common ITS sequence type was observed in two of the patients with haematological malignancies who shared a hospital room, and also in two of the patients with HIV infection who had prolonged close contact on the ward. In contrast, different ITS sequence types were detected in samples from an HIV-infected homosexual couple who shared the same household. These data suggest that person-to-person transmission of P. carinii sp. f. hominis may occur from infected to susceptible immunosuppressed patients with close contact within hospital environments. However direct transmission between patients did not account for the majority of cases within the clusters, suggesting that person-to-person transmission of P. carinii sp. f. hominis infection may be a relatively infrequent event and does not constitute the major route of transmission in man.

AIDS-Related Opportunistic Infections↗
PubMed2006

Molecular insights into the self-assembly mechanism of dystrophia myotonica kinase.

Self-assembly via coiled-coil domains (CC) is crucial for the regulation of the dystrophia myotonica kinase (DMPK) -related family of kinases. These CC domains are thought to form dimeric arrangements and thus to mediate dimerization in these enzymes. Using size exclusion chromatography combined with multiangle static light scattering, we analyzed the oligomeric state of DMPK as well as that of a truncated variant lacking the CC fraction. Remarkably, both forms were found to assemble into robust dimers. In contrast, the CC domain in isolation yielded trimeric assemblies, indicating that the oligomerization properties of CC domains from this kinase family are more diversified than anticipated. The crystal structure of this CC has been elucidated to 1.6 angstroms resolution and its properties in solution established using sedimentation equilibrium and thermal denaturation. These data show that, contrary to expectations, the self-assembly of DMPK is not dictated by the association properties of its CC domain. Instead, it appears to be driven by sequence segments flanking both N and C termini of the catalytic kinase fraction, as suggested by models of head-to-head dimers based on small angle X-ray scattering data. Our findings support a shared pattern of assembly across DMPK, ROCKs, and MRCK members of this family.

Animals↗
PubMed1996

Perception, reality, and the political context of conflict of interest in university-industry relationships.

The crucial issues in a policy debate are often matters of perception and interpretation rather than fact, and the values and norms that influence perceptions are central to an understanding of conflict in the policy arena. For example, science's norms of objectivity and disinterestedness are being modified today to accommodate closer academic-industry ties. The author traces in detail how these ties and the accompanying public distrust have developed, beginning with the post-World-War-II increase in public support for basic research and continuing with subsequent pieces of legislation that lowered the barriers between academic and industrial research in order to reap economic benefits. He then analyzes the impact of financial incentives in university-industry relationships on science and on public perceptions of science, and the price both science and the public would pay if the public loses trust in science and refuses to support it. He also reviews the history of the ill-fated National Institutes of Health guidelines for university-industry collaborations proposed in 1979 and the subsequent history of the policy on this topic recently adopted by the Public Health Service. He maintains that the PHS policy poses both a risk (the temptation to enforce the policy loosely) and an opportunity (for research institutions to grasp the initiative and develop meaningful conflict-of-interest guidelines of their own). But the policy falls short of responding to the much broader range of concerns associated with university-industry research collaboration, for example, the possible effects of such collaboration on the traditional openness and sharing among scientists. The available data on these effects are mixed. He concludes by maintaining that scientists and their industry partners should address the issues surrounding their collaboration now rather than waiting for negative events to trigger public arousal and force a mutually unsatisfying political solution. This article is one of three in this issue of Academic Medicine that deal with issues of conflict of interest in university-industry research relationships. These articles are discussed in an overview that precedes them.

Biomedical Research↗
PubMed1995

Functions of a breast cancer support group as perceived by the participants: an ethnographic study.

The purpose of this study was to obtain an understanding of the functions of a breast cancer support group as perceived by the participants. An ethnographic method of research was used. Data were collected by participant observation and tape-recorded interviews during the weekly support group meetings. The convenience sample included one professional group leader and 15 women diagnosed with breast cancer within a range of 2 weeks to 7 years. Two key informants were chosen to clarify and validate data. Content analysis was performed on the data obtained from the tape recordings of 10 group meetings and from the two key informant interviews. Three categories of functions of the breast cancer support group emerged from the data analysis, including exchanging information, sharing the illness experience, and providing strength. As the incidence rate of breast cancer continues to increase, it is imperative that nurses recognize the physical and psychological reactions to breast cancer and identify sources of social support for women. Nurses should be cognizant of the functions of a breast cancer support group in order to share this information with women and encourage them to actively participate with others sharing the same experience.

Adult↗
PubMed1998

Pediatric facial fractures: analysis of differences in subspecialty care.

At the University of Michigan, the pediatric facial fracture call schedule rotates through the plastic surgery, otolaryngology, and oral surgery services. This situation provides an opportunity to evaluate differences in the management of pediatric facial fractures between subspecialty groups. At this hospital, a retrospective review of all pediatric facial fracture cases within a 5-year period was undertaken. Sixty patients with 82 facial fractures were studied along subspecialty lines. Differences in patient groups, practice patterns, and treatment strategies based on subspecialty assignment were found. Overall treatment followed traditional lines, with plastic surgeons involved in all types of pediatric facial fractures, whereas otolaryngology and oral surgeons were more limited in their operative scope, despite equal call responsibilities. It is believed that the managed care arena is a competitive environment in which it will be important to know the strengths and weaknesses of the plastic surgery specialty, as well as those of competing specialties, as patient contracts are negotiated. The overlap of plastic surgery, otolaryngology, and oral surgery in the care of facial trauma could result in plastic surgeons being left off of managed care participant lists. This study highlights plastic surgeons as efficient deliverers of quality care for pediatric facial fractures. Although the treatment of these fractures has fallen into the duties shared by all three subspecialties, data such as those presented here should strengthen our ability to succeed in the evolving environment of managed care.

Adolescent↗
PubMed2002

Multibeam stimulated brillouin scattering from hot, solid-target plasmas.

We report on multibeam, laser-plasma interaction experiments in plasmas relevant to future direct-drive-ignition experiments. Six interaction beams are incident on preformed plasmas containing critical density. Stimulated Brillouin scattering (SBS) shows strong evidence of electromagnetic wave seeding of side- and backscattering. The data are also consistent with shared ion waves driven by the six symmetrically arranged interaction beams. Early SBS quenching is observed and attributed to the hydrodynamics of the plasma.

Journal Article↗
PubMed1997

Differential stimulation of ERK and JNK activities by ultraviolet B irradiation and epidermal growth factor in human keratinocytes.

Exposure of mammalian cells to solar ultraviolet (UV) radiation leads to the expression of several genes, and UV has been recognized as a major initiator and promoter of skin cancer. The component of the solar radiation that contributes most to human skin malignancy is UVB (280-320 nm) and, to a lesser extent, UVA (320-400 nm), whereas the high-energy UVC (100-280 nm) is absorbed by the earth's upper atmosphere. Sublethal doses of UVB produce strong induction of c-jun and c-fos transcripts in several cells including human primary keratinocytes. The present report confirms that this is also the case in the HaCaT cell line and shows that similar UVB doses are potent inducers of the JNK/SAPK family of mitogen-activated protein kinases but only weak activators of ERKs. Epidermal growth factor (EGF) caused rapid induction of both JNK- and ERK-signaling pathways, and the downmodulation of the EGF-signaling pathway by EGF pre-treatment inhibited the UVB-induced JNK1 activation. Prior UVB irradiation of the cells decreased the level of the ERK2 activation by a subsequent EGF treatment, but this sensitized the cells and allowed for the super-activation of JNK1 after a rechallenge with either UVB or EGF. The antioxidant N-acetylcysteine impaired the UVB- and EGF-induced activation of JNK1. Our data suggest the presence of shared signaling component(s) in the UVB- and EGF-induced cellular response pathways and imply that oxidative stress plays a significant role in the activation of JNK1 by UVB and EGF.

Base Sequence↗
PubMed1990

Sexual partners of injecting drug users: the risk of HIV infection.

The sexual mediation of HIV infection by injecting drug users to the heterosexual population has become a major issue in AIDS prevention. Infection that is acquired through sharing contaminated injecting equipment can be passed on to non-injecting drug using partners and to non-drug using partners through sexual intercourse. A study of risk behaviour among injecting drug users in the North West of England focused, inter alia, upon aspects of their sexual activity and attitudes that have relevance for HIV transmission. It was found that in those respondents with regular partners, the level of sexual activity was related to the partner's use of drugs. The use of condoms was low in the sample as a whole, including those who reported having casual sexual contacts and sharing others' injecting equipment. These data confirm the need for concern and the advisability of targetting safer-sex education on drug users.

Adult↗
PubMed2006

Developmental expression of Na+ currents in mouse Purkinje neurons.

As Purkinje neurons mature during postnatal development, they change from electrically quiescent to active and exhibit high frequency spontaneous action potentials. This change in electrical activity is determined by both alteration in ion channel expression and the acquisition of synaptic input. To gain a better understanding of the development the intrinsic electrical properties of these neurons, acutely isolated Purkinje neurons from mice aged postnatal day 4 (P4) to P18 were examined. This included recording action potential frequency, threshold, height and slope, and input resistance and capacitance. Changes in a number of these properties were observed, suggesting significant changes in voltage-gated Na(+) currents. Because voltage-gated Na(+) currents, including the transient, resurgent and persistent currents, are known to play important roles in generating spontaneous action potentials, the developmental changes in these currents were examined. A large increase in the density of transient current, resurgent current and persistent current was observed at times corresponding with changes in action potential properties. Interestingly, the developmental up-regulation of the persistent current and resurgent current occurred at rate which was faster than the up-regulation of the transient current. Moreover, the relative amplitudes of the persistent and resurgent currents increased in parallel, suggesting that they share a common basis. The data indicate that developmental up-regulation of Na(+) currents plays a key role in the acquisition of Purkinje neuron excitability.

Action Potentials↗