A randomised controlled trial of psychological debriefing for victims of road traffic accidents.
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Accidents, Traffic↗
Biomedical subjects
M Hobbs
Publications and source records attributed to M Hobbs.
Relations of changes in coronary disease rates and changes in risk factor levels: methodological issues and a practical example.
One of the main hypotheses of the World Health Organization (WHO) MONICA Project is that trends in the major coronary disease risk factors are related to trends in rates of fatal and non-fatal coronary disease events. The units of study are populations rather than individuals. The WHO MONICA Project involves continuous monitoring of all coronary disease events in the populations over a 10-year period and periodic risk factor surveys in random samples of the same populations. Estimation of associations between average annual changes in mortality and risk factor levels is illustrated with the use of data from a subset of MONICA centers. Crude estimates of regression coefficients are compared with estimates obtained by weighting for standard errors in both the outcome and explanatory variables. The results show that the strength of association may be either underestimated or overestimated if these errors are not taken into account.
Adult↗
Organization of the Escherichia coli K-12 gene cluster responsible for production of the extracellular polysaccharide colanic acid.
Colanic acid (CA) is an extracellular polysaccharide produced by most Escherichia coli strains as well as by other species of the family Enterobacteriaceae. We have determined the sequence of a 23-kb segment of the E. coli K-12 chromosome which includes the cluster of genes necessary for production of CA. The CA cluster comprises 19 genes. Two other sequenced genes (orf1.3 and galF), which are situated between the CA cluster and the O-antigen cluster, were shown to be unnecessary for CA production. The CA cluster includes genes for synthesis of GDP-L-fucose, one of the precursors of CA, and the gene for one of the enzymes in this pathway (GDP-D-mannose 4,6-dehydratase) was identified by biochemical assay. Six of the inferred proteins show sequence similarity to glycosyl transferases, and two others have sequence similarity to acetyl transferases. Another gene (wzx) is predicted to encode a protein with multiple transmembrane segments and may function in export of the CA repeat unit from the cytoplasm into the periplasm in a process analogous to O-unit export. The first three genes of the cluster are predicted to encode an outer membrane lipoprotein, a phosphatase, and an inner membrane protein with an ATP-binding domain. Since homologs of these genes are found in other extracellular polysaccharide gene clusters, they may have a common function, such as export of polysaccharide from the cell.
Acetyltransferases↗
Anatomical correlates of the passive properties underlying the developmental shift in the frequency map of the mammalian cochlea.
As the cochlea develops, the cells in the basal cochlea become sensitive to progressively higher frequencies. To identify features of cochlear morphology that may underlie the place code shift, measurements of infant and adult gerbil cochleas were made at both the light and electron microscopic levels. The measurements included areas of the cochlear duct, basilar membrane, and organ of Corti, height and width of the basilar membrane, thickness of the tympanic cover layer, thickness of the upper and lower basilar membrane fiber bands, and optical density of the basilar membrane. The results indicated that basilar membrane dimensions do not change as the place code shifts and that regions that code for the roughly the same frequency (e.g., approximately 11.2 kHz) at different ages can have basilar membranes of very different dimensions. In contrast, the size of the organ of Corti and the thickness of fiber bands inside the basilar membrane do change in ways consistent with the shift in the frequency map.
Acoustic Stimulation↗
Genetic organisation and evolution of Yersinia pseudotuberculosis 3,6-dideoxyhexose biosynthetic genes.
3,6-dideoxyhexose (DDH) sugars occur in some of the O antigens of Salmonella enterica and Yersinia pseudotuberculosis, but are otherwise rarely found in nature. Y. pseudotuberculosis DDH biosynthetic genes rfbS (encoding CDP-paratose synthetase) and rfbE (encoding CDP-tyvelose epimerase) were amplified and cloned, and their sequences determined. Comparisons with the equivalent genes of S. enterica show that the genetic arrangement of DDH genes is very similar; however, in Y. pseudotuberculosis there is no suggestion that paratose producing strains are derived from tyvelose-producing strains by inactivation of rfbE, which is the case in S. enterica. The previously determined DNA sequence of the rfb region of an abequose-producing strain was re-examined. It contains the remnants of an insertion sequence (IS) adjacent to a truncated and non-functional rfbE gene. This suggests that the IS was involved in recombination events contributing to O-antigen antigenic diversity in Y. pseudotuberculosis.
Amino Acid Sequence↗
A model for mixed virus disease: co-infection with Moloney murine leukemia virus potentiates runting induced by polyomavirus (A2 strain) in Balb/c and NIH Swiss mice.
Polyomavirus was originally isolated by Ludwick Gross from a mixture that also contained a murine retrovirus. A possible pathogenic interaction between polyomavirus and an endogenous mouse retrovirus locus (mtv-7) in polyomavirus-induced cancer has also been reported. To study potential interactive effects of polyomavirus (Py) and Moloney murine leukemia retrovirus (M-MuLV), newborn Balb/c and NIH Swiss mice were infected with high titer wild-type Py (A2 strain) and M-MuLV. Dramatically stunted growth (runting) occurred in 100% of the doubly inoculated mice, while much lower frequency of runting occurred in animals infected with Py alone and not at all with M-MuLV-infected mice. In situ hybridization for Py DNA showed ongoing Py replication and inflammation in kidneys (atypical of most mice singly infected by Py) of runted doubly inoculated mice. In addition, high Py viral replication continued well past the usual acute stage termination. M-MuLV replication was also initially inhibited in bone marrow by simultaneous Py infection. No M-MuLV replication was seen in singly or doubly infected mouse kidneys. Runting was very rapid, observable within 2 days after co-infection, arguing against an adaptive or antigen-specific immunological mechanism. One possibility was that a cytokine-driven acute response mechanism was involved. Supporting this view, RNAse protection assays for various cytokine RNAs showed that several were specifically elevated in kidneys of doubly infected mice. Three patterns were observed: (1) IL-6 was elevated in doubly infected mice early after infection (7 days), but it declined at later times (19 days); (2) IFN-gamma, IL-1 beta, and IL-10 were elevated at both early and late times; and (3) TNF-alpha, IL-12p40, and possibly TNF-beta were elevated only at late times. While the cytokines in the third category might be indicative of infiltrating inflammatory cells, it seems possible that cytokines in the first or second categories might be involved in establishing runting and ongoing polyoma DNA replication in the doubly infected mice.
Animals↗
Successful interviewing and selection strategies for patient-centered care delivery.
St. Jude Medical Center, a Sisters of St. Joseph Health System Corporation in Fullerton California, in their efforts at work redesign, realized that the success of a patient-centered care delivery system largely depended upon successful selection of the most suitable team members. The interviewing and selection process used at St. Jude Medical Center includes a structured interview process with integration of both situational and behavioral styles in conjunction with objective rating scales and values driven questions. A common thread woven into the hiring criteria for all levels of personnel in the patient-centered care delivery model was creativity, adaptability, interpersonal skills and compatibility of values. Additionally, the clinical competence of the caregiver within the scope of practice/responsibility was essential for their expanded role. Management and leadership abilities for the managers are also addressed in the interview and selection process to provide the best team members for the overall success of the patient-care redesign.
Humans↗
Isolation of a diverged homeobox gene, MOX1, from the BRCA1 region on 17q21 by solution hybrid capture.
Using the technique of solution hybridization coupled with magnetic bead capture, we have isolated a novel homeobox-containing gene from the BRCA1 region of 17q21. This gene is the human homologue of the mouse Mox1 gene previously localized to a syntenic region of mouse chromosome 11. Multiple overlapping cDNAs of human MOX1 were identified using both a cosmid and a P1 genomic clone containing the microsatellite markers D17S750 and D17S858 which map within the BRCA1 region defined by D17S776 and D17S78. MOX1 expression was observed in a variety of normal tissues examined, including breast and ovary. Given that the gene contains a homeobox domain and has the potential to regulate growth and differentiation, MOX1 represents an attractive candidate for the BRCA1 gene. This possibility was investigated in a series of BRCA1 kindreds and primary sporadic breast tumors. No evidence for mutation was found in the coding sequence, making it unlikely that MOX1 is the BRCA1 gene. However, the widespread expression of MOX1 in non-embryonal tissues suggests a role in normal cell biology which warrants further study.
Amino Acid Sequence↗
The JUMPstart sequence: a 39 bp element common to several polysaccharide gene clusters.
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Base Sequence↗
Structure of the O antigen of Escherichia coli K-12 and the sequence of its rfb gene cluster.
Escherichia coli K-12 has long been known not to produce an O antigen. We recently identified two independent mutations in different lineages of K-12 which had led to loss of O antigen synthesis (D. Liu and P. R. Reeves, Microbiology 140:49-57, 1994) and constructed a strain with all rfb (O antigen) genes intact which synthesized a variant of O antigen O16, giving cross-reaction with anti-O17 antibody. We determined the structure of this O antigen to be -->2)-beta-D-Galf-(1-->6)-alpha-D-Glcp- (1-->3)-alpha-L-Rhap-(1-->3)-alpha-D-GlcpNAc-(1-->, with an O-acetyl group on C-2 of the rhamnose and a side chain alpha-D-Glcp on C-6 of GlcNAc. O antigen synthesis is rfe dependent, and D-GlcpNAc is the first sugar of the biological repeat unit. We sequenced the rfb (O antigen) gene cluster and found 11 open reading frames. Four rhamnose pathway genes are identified by similarity to those of other strains, the rhamnose transferase gene is identified by assay of its product, and the identities of other genes are predicted with various degrees of confidence. We interpret earlier observations on interaction between the rfb region of Escherichia coli K-12 and those of E. coli O4 and E. coli Flexneri. All K-12 rfb genes were of low G+C content for E. coli. The rhamnose pathway genes were similar in sequence to those of (Shigella) Dysenteriae 1 and Flexneri, but the other genes showed distant or no similarity. We suggest that the K-12 gene cluster is a member of a family of rfb gene clusters, including those of Dysenteriae 1 and Flexneri, which evolved outside E. coli and was acquired by lateral gene transfer.
Acetylation↗
Molecular analysis of the rfb gene cluster of a group D2 Salmonella enterica strain: evidence for its origin from an insertion sequence-mediated recombination event between group E and D1 strains.
The Salmonella enterica O antigen is a highly variable surface polysaccharide composed of a repeated oligosaccharide (the O unit). The O unit produced by serogroup D2 has structural features in common with those of groups D1 and E1, and hybridization studies had previously suggested that the D2 rfb gene cluster responsible for O-unit biosynthesis is indeed a hybrid of the two. In this study, the rfb gene cluster was cloned from a group D2 strain of S. enterica sv. Strasbourg. Mapping, hybridization, and DNA sequencing showed that the organization of the D2 rfb genes is similar to that of group D1, with the alpha-mannosyl transferase gene rfbU replaced by rfbO, the E1-specific beta-mannosyl transferase gene. The E1-specific polymerase gene (rfc) has also been acquired. Interestingly, the D1-like and E1-like rfb regions are separated by an additional sequence closely related to an element (Hinc repeat [H-rpt]) associated with the Rhs loci of Escherichia coli. The H-rpt resembles an insertion sequence and possibly mediated the intraspecific recombination events which produced the group D2 rfb gene organization.
Amino Acid Sequence↗
Elevation of cysteine and replenishment of glutathione in rat lung slices by cysteine isopropylester and other cysteine precursors.
In this study, we have used a rat lung slice model to compare the ability to several potential cysteine delivery systems (L-cysteine isopropylester, L-cysteine cyclohexylester, N-acetylcysteine, L,2-oxo-4-thiazolidine carboxylic acid and cysteine) to elevate cysteine and glutathione (GSH) levels in control lung slices and slices depleted of their GSH by diethyl maleate. The esters of cysteine produced the greatest rise in lung slice cysteine. All the cysteine delivery systems were capable of replenishing GSH in lung slices previously depleted of GSH by diethyl maleate.
Acetylcysteine↗
The expression of CD45RB on antigen-responsive CD4+ lymphocytes: mouse strain polymorphism and different responses to distinct antigens.
The levels of CD45RB expression by HGG-specific CD4+ cells residing in the Ag-draining lymph nodes of HGG-primed CBA/CaJ mice were analyzed. When sorted populations of CD4+, CD45RBhi, and CD4+, CD45RBlo cells were cultured with HGG and Ag-presenting cells, the majority of the proliferative response was found in the CD45RBlo fraction early after in vivo priming (Day 6), and this pattern remained stable through 12 days postpriming. To determine whether this segregation of responsiveness was consistent in other mouse strains, HGG-primed C57BL/6J mice were similarly analyzed. In contrast to findings with the CBA/CaJ strain, the CD4+, CD45RBhi cell fraction obtained from C57BL/6J mice was the predominant responding population early after in vivo priming (Day 6); however, there was a parallel increase in responsiveness of CD4+, CD45RBhi, and CD4+, CD45RBlo cells by Day 12. Thus, there was not a decrease in CD45RBhi expression with a concommitant increase in CD45RBlo expression in CD4+ cells proliferating to HGG. Despite the heterogeneity in CD45RB expression by the primed CD4+ cells of the two strains, the entire proliferative response to HGG early after priming resided in the fraction bearing high levels of membrane CD44, thus arguing for the existence of CD45RBhi, CD44hi and CD45RBlo, CD44hi cells during the early phase of the response. In both mouse strains the CD4+, CD45RBhi subset of primed lymph node cells produced significant levels of IL-2 in response to HGG and APC, whereas no significant IL-2 or IL-4 production was detectable in HGG-stimulated CD45RBlo cells of either strain. The CD4+, CD45RBhi subset also proliferated more vigorously in response to polyclonal activation than the CD4+ CD45RBlo fraction. To examine whether the patterns of CD45RB expression on HGG-primed cells from C57BL/6J mice were common to other antigens, the response profiles were examined after in vivo priming with a second antigen, KLH. In contrast to studies with HGG as the Ag, the proliferative response to KLH in C57BL/6J mice was evenly divided among the CD45RBhi and CD45RBlo fractions on Day 8 after priming, but shifted markedly to the CD45RBlo fraction by Day 12 after priming. Taken together, these data show that the patterns of CD45RB expression on primed populations of CD4+ cells can exhibit mouse strain polymorphism and can differ depending on the choice of antigen for immunization.
Animals↗
PilS and PilR, a two-component transcriptional regulatory system controlling expression of type 4 fimbriae in Pseudomonas aeruginosa.
Transposon mutagenesis was used to identify genes necessary for the expression of Pseudomonas aeruginosa type 4 fimbriae. In a library of 12,700 mutants, 147 were observed to have lost the spreading colony morphology associated with the presence of functional fimbriae. Of these, 28 had also acquired resistance to the fimbrial-specific bacteriophage PO4. The mutations conferring this phage resistance were found to have occurred at at least six different loci, including the three that had been previously shown to be required for fimbrial biosynthesis or function: the structural subunit (pilA) and adjacent genes (pilB,C,D), the twitching motility gene (pilT), and the sigma 54 RNA polymerase initiation factor gene (rpoN). One novel group of phage-resistant mutants was identified in which the transposon had inserted near sequences that cross-hybridized to an oligonucleotide probe designed against conserved domains in regulators of RpoN-dependent promoters. These mutants had no detectable transcription of pilA and did not produce fimbriae. A probe derived from inverse polymerase chain reaction was used to isolate the corresponding wild-type sequences from a P. aeruginosa PAO cosmid reference library, and two adjacent genes affected by transposon insertions, pilS and pilR, were located and sequenced. These genes were shown to be capable of complementing the corresponding mutants, both at the level of restoring the phenotypes associated with functional fimbriae and by the restoration of pilA transcription. The pilSR operon was physically mapped to Spel fragment 5 (corresponding to about 72-75/0 min on the genetic map), and shown to be located approximately 25 kb from pilA-D. PilS and PilR clearly belong to the family of two-component transcriptional regulatory systems which have been described in many bacterial species. PilS is predicted to be a sensor protein which when stimulated by the appropriate environmental signals activates PilR through kinase activity. PilR then activates transcription of pilA, probably by interacting with RNA polymerase containing RpoN. The identification of pilS and pilR makes possible a more thorough examination of the signal transduction systems controlling expression of virulence factors in P. aeruginosa.
Amino Acid Sequence↗
Characterization of pilQ, a new gene required for the biogenesis of type 4 fimbriae in Pseudomonas aeruginosa.
Type 4 fimbriae are produced by a variety of pathogens, in which they appear to function in adhesion to epithelial cells, and in a form of surface translocation called twitching motility. Using transposon mutagenesis of Pseudomonas aeruginosa, we have identified a new locus required for fimbrial assembly. This locus contains the gene pilQ which encodes a 77 kDa protein with an N-terminal hydrophobic signal sequence characteristic of secretory proteins. pilQ mutants lack the spreading colony morphology characteristic of twitching motility, are devoid of fimbriae, and are resistant to the fimbrial-specific bacteriophage PO4. The pilQ gene was mapped to Spel fragment 2, which is located at 0-5 minutes on the P. aeruginosa PAO1 chromosome, and thus it is not closely linked to the previously characterized pilA-D, pilS,R or pilT genes. The pilQ region also contains ponA, aroK and aroB-like genes in an organization very similar to that of corresponding genes in Escherichia coli and Haemophilus influenzae. The predicted amino acid sequence of PilQ shows homology to the PulD protein of Klebsiella oxytoca and related outer membrane proteins which have been found in association with diverse functions in other species including protein secretion, DNA uptake and assembly of filamentous phage. PilQ had the highest overall homology to an outer membrane antigen from Neisseria gonorrhoeae, encoded by omc, that may fulfil the same role in type 4 fimbrial assembly in this species.
Amino Acid Sequence↗
Common components in the assembly of type 4 fimbriae, DNA transfer systems, filamentous phage and protein-secretion apparatus: a general system for the formation of surface-associated protein complexes.
The Pseudomonas aeruginosa genes pilB-D and pilQ are necessary for the assembly of type 4 fimbriae. Homologues of these genes and of the subunit (pilin) gene have been described in various different bacterial species, but not always in association with type 4 fimbrial biosynthesis and function. Pil-like proteins are also involved in protein secretion, DNA transfer by conjugation and transformation, and morphogensis of filamentous bacteriophages. It seems likely that the Pil homologues function in the processing and export of proteins resembling type 4 fimbrial subunits, and in their organization into fimbrial-like structures. These may either be true type 4 fimbriae, or components of protein complexes which act in the transport of macromolecules (DNA or protein) into or out of the cell. Some PilB-like and PilQ-like proteins are apparently also involved in the assembly of non-type 4 polymeric structures (filamentous phage virions and conjugative pili). The diverse studies summarized in this review are providing insight into an extensive infrastructural system which appears to be utilized in the formation of a variety of cell surface-associated complexes.
Amino Acid Sequence↗
Medical care and case fatality from myocardial infarction and coronary death in Newcastle and Perth.
Coronary mortality rates are significantly higher in Newcastle than Perth. In this paper we examine the extent to which this might be due to differences in medical treatment and case fatality. Population-based disease registers were used to identify all cases of non-fatal definite myocardial infarction (MI) and coronary death in people aged 25-64 years in the study populations between July 1988 and June 1990. Case fatality (at 28 days from onset of symptoms) was not significantly different between the centres. Thrombolytic therapy was used for one third of all hospitalised events in both centres. Other drugs of proven benefit were, however, used more often in Perth than in Newcastle. For example, during hospitalisation 74% of patients in Perth received beta-blockers compared with 41% in Newcastle (difference = 33%, 95% confidence interval (CI): 28%, 37%) and 85% of patients in Perth compared with 72% in Newcastle received aspirin (difference = 13%, 95% CI: 9%, 17%). Median lengths of stay in a coronary care unit (CCU) and total hospital stay were one day shorter in Perth. As case fatality was similar, the differences in mortality rates can be attributed mainly to differences in attack rates. Greater use of cardio-active drugs in Perth apparently did not result in improved short-term outcome although potential long-term benefits cannot be judged yet.
Adult↗
Recognising and managing depression in general practice.
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Depression↗