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M Hobbs

Publications and source records attributed to M Hobbs.

At least 37 records · Page 2Linked to original sources
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

Review of the benefits of treating hypertension.

The main points covered in this review are as follows: 1. Hypertension is a major determinant of cardiovascular disease (CVD). As such it is a major cause of mortality, potential years of life lost, morbidity and long-term disability. 2. The incidence of CVD is directly related to BP. It is likely that this extends over the full range of BP although some writers believe that a J-curve of risk exists for CHD. 3. The relationship between long-term disability from CVD and BP requires further study. 4. Because of regression dilution bias, the gradient in risk of stroke and CHD with BP has been underestimated in the past. Recent research suggests that the risk of stroke increases at least tenfold and CHD sixfold over a range of usual DBP of 30 mmHg (equivalent to approximately 50 mmHg baseline DBP). 5. The population attributable risk (PAR) of CVD related to general elevation of BP in the population from a mean daily excess of sodium intake of 100 mmol/day is at least 30%. In typical industrialised countries the PAR for stroke and CHD from clinical hypertension is 36% and 22%, respectively. These estimates of PAR provide a guide to the maximum benefit that could result from either restriction of sodium intake in the whole population or ideal management of all persons with hypertension. In practice such targets are unlikely to be realised. 6. Recent analyses of clinical trials of treatment of hypertension suggest that the risk of stroke is reduced at all levels of initial BP to the extent predicted from observational studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1991

Characterisation of a Pseudomonas aeruginosa twitching motility gene and evidence for a specialised protein export system widespread in eubacteria.

Type-4 fimbriae (pili) are associated with a phenomenon known as twitching motility, which appears to be involved with bacterial translocation across solid surfaces. Pseudomonas aeruginosa mutants which produce fimbriae, but which have lost the twitching motility function, display altered colony morphology and resistance to fimbrial-specific bacteriophage. We have used phenotypic complementation of such mutants to isolate a region of DNA involved in twitching motility. This region was physically mapped to a SpeI fragment around 20 min on the P. aeruginosa PAO chromosome, remote from the major fimbrial locus (around 75 min) where the structural subunit-encoding gene (fimA/pilA) and ancillary genes required for fimbrial assembly (pilB, C and D) are found. A gene, pilT, within the twitching motility region is predicted to encode a 344-amino acid protein which has strong homology to a variety of other bacterial proteins. These include the P. aeruginosa PilB protein, the ComG ORF-1 protein from the Bacillus subtilis comG operon (necessary for competence), the PulE protein from the Klebsiella oxytoca (formerly K. pneumoniae) pulC-O operon (involved in pullulanase export), and the VirB-11 protein from the virB operon (involved in virulence) which is located on the Agrobacterium tumefaciens Ti plasmid. We have also identified other sets of homologies between P. aeruginosa fimbrial assembly (Pil) proteins and B. subtilis Com and K. oxytoca Pul proteins, which suggest that these are all related members of a specialised protein export pathway which is widespread in the eubacteria.

Amino Acid Sequence↗
PubMed1991

Organization of the fimbrial gene region of Bacteroides nodosus: class I and class II strains.

The fimbrial subunit genes of Bacteroides nodosus may be divided into two distinct classes, based on the sequence of the major subunit gene fimA (accompanying paper--Mattick et al., 1991). The genetic organization of the fibrial gene region in these two classes is also distinct. Upstream of fimA in both classes in opposite transcriptional orientation is the gene aroA which encodes amino acid biosynthetic enzyme 5-enolpyruvylshikimate-3-phosphate synthase. However, downstream of fimA the two classes are quite different until homology is restored at a bidirectional transcription termination signal separating the fimbrial operon from a gene clpB, which appears to encode the regulatory subunit of an ATP-dependent protease. Between aroA and clpB class I strains contain, apart from fimA, only one other gene (fimB). Sequence and polymerase chain reaction analyses indicate that fimB does not have a separate promoter but rather is co-transcribed with fimA at a level attenuated by the strength of the transcription termination signal in the intergenic region. In class II strains fimA is followed by a more extended region containing three genes, which appear to have the same transcriptional arrangement as fimB. The second of these genes (fimD) may represent a functional analogue of fimB although there is no close sequence homology. The first gene (fimC) has no obvious similarity to either fimB or fimD. Beyond fimD, at the 3' end of the class II-specific region, is a variant fimbrial subunit gene (fimZ) which is virtually identical in serogroups D and H and which appears to represent a duplicate, possibly redundant, gene closely related to the progenitor of the more divergent structural subunit fimA gene found in these strains. Comparisons of the predicted fimZ product with those of fimA in class I and class II strains, as well as of the boundaries of the class-specific regions, suggest that the class II sequences evolved in another type 4 fimbriate species and were subsequently substituted in the B. nodosus genome by lateral transfer. Analysis of the sequences flanking fimA in different strains indicates that recombinational exchange of both fimA and the entire operon has also occurred between strains, and is possibly a mechanism for disseminating structural diversity in the population.

Amino Acid Sequence↗
PubMed1991

Gene sequences and comparison of the fimbrial subunits representative of Bacteroides nodosus serotypes A to I: class I and class II strains.

We have determined the nucleotide sequences of the genes encoding the fimbrial subunits representative of the known Bacteroides nodosus serogroups. All of the genes are preceded by a highly conserved region which includes the likely promoter and transcriptional regulator sites as well as the ribosome-biding site, and are followed within a short but variable distance by a sequence with the characteristics of a transcription termination or attenuation signal. Based on sequence and organization, the subunits can be divided into two major classes called I (serogroups A, B, C, E, F, G, and I) and II (serogroups D and H). All contain the same seven-amino-acid positively charged leader sequence and conserved hydrophobic amino-terminal sequence typical of type 4 fibriae. Beyond this point the class II subunits are quite different from class I and share features more in common with those from other type 4 fimbriate bacteria, such as Moraxella bovis and Pseudomonas aeruginosa. The larger class I may be further subdivided into two subsets: (i) [A, E, F)(B, I)) and (ii) (C, G). These proteins exhibit three major clusters of variation, at either end of the presumptive disulphide loop which spans the central third of the protein, and near the carboxy-terimus, with dispersed changes in between. The length of the mature subunits varies from 152-156 amino acids, and the variation includes small insertions or deletions in the variable clusters between more conserved domains. The class II subunits are 149 amino acids in length and contain two pairs of cysteine residues: one is at the end of the amino-terminal conserved region, and the other is at the end of the protein. The major variation occurs in the central region of the molecule, and again small insertions or deletions are required to align adjacent conserved domains. There is also a striking absence of silent codon changes in the 5' coding region of all of these genes, indicating that these sequences have a secondary genetic function, probably in recombinational exchange.

Amino Acid Sequence↗
PubMed1990

Conservation of the regulatory subunit for the Clp ATP-dependent protease in prokaryotes and eukaryotes.

Bacteria, tomatoes, and trypanosomes all contain genes for a large protein with extensive homology to the regulatory subunit, ClpA, of the ATP-dependent protease of Escherichia coli, Clp. All members of the family have between 756 and 926 amino acids and contain two large regions, of 233 and 192 amino acids, each containing consensus sequences for nucleotide binding. Within these regions there is at least 85% similarity between the most distant members of the family. The high degree of similarity among the ClpA-like proteins suggests that Clp-like proteases are likely to be important participants in energy-dependent proteolysis in prokaryotic and eukaryotic cells.

ATP-Dependent Proteases↗