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Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 127 records · Page 7Linked to original sources
PubMed1997

The validity of surgical wound infection as a clinical indicator in Australia.

BACKGROUND: Evidence-based medicine and measurement of outcome have become the foremost strategy of departments of health and quality care in Australia in the 1990s. The Australian Council of Healthcare Standards, (ACHS), formed in 1974, has introduced a Clinical Indicators Programme which monitors a number of clinical outcomes, including rates of specific nosocomial infections. It is the only formal system in Australia which attempts to monitor nosocomial infection in hospitals, and the ACHS acknowledges that the data provided to them are collected using a variety of sources and definitions. METHODS: The present study discusses the validity of the present definitions of nosocomial surgical wound infection used for accreditation, how validity may be improved and the attempts by some international systems to improve their own data. RESULTS: The ACHS definitions of nosocomial surgical wound infection lack validity, and the rates provided lack generalizability. Several international surveillance systems have resources in place to provide members with standardized training for practitioners, and support for methodology, data analysis and reporting, which assists in improving the quality of the data collected. CONCLUSION: It is our belief that the validity of surgical wound infections will be improved by adoption of National Nosocomial Infection Surveillance (NNIS) definitions, stratification of surgical wound infections by anatomical site of infection for sentinel procedures. The ACHS system must adopt the proposed changes if the rates are to be used as a local and national indicator.

Australia↗
PubMed1997

Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture?

Physical disruption of an atheromatous lesion often underlies acute coronary syndromes. Matrix-degrading enzymes, eg, matrix metalloproteinases (MMPs), may cause loss in mechanical integrity of plaque tissue that favors rupture. T lymphocytes accumulate at sites where atheromata rupture, but the mechanisms by which these immune cells may contribute to plaque destabilization are unknown. This study tested the hypothesis that the T-lymphocyte surface molecule CD40 ligand (CD40L), recently localized in atherosclerotic plaques, regulates the expression of MMPs in human vascular smooth muscle cells (SMCs), the most numerous cell type in arteries. We report here that stimulated human T lymphocytes induced the expression of the matrix-degrading enzymes, ie, interstitial collagenase (MMP-1), stromelysin (MMP-3), gelatinase B (MMP-9), and activated gelatinase A (MMP-2), in human vascular SMCs by cell contact via CD40 ligation, as demonstrated by Western blot analysis, zymography, and antibody neutralization. Recombinant human CD40L (rCD40L) induced de novo synthesis of MMP-1, MMP-3, and MMP-9 on vascular SMCs and stimulated the expression of these enzymes to a greater extent than did maximally effective concentrations of tumor necrosis factor-alpha or interleukin-1beta, established agonists of MMP expression. Interferon gamma, another T-lymphocyte- derived cytokine, inhibited the induction of MMPs by rCD40L. Immunohistochemical analysis of human coronary atheromata colocalized MMP-1 and MMP-3 with CD40-positive SMCs. These results demonstrated that CD40 ligand, expressed on T lymphocytes, promoted the expression of matrix-degrading enzymes in vascular SMCs and thus established a new pathway of immune-modulated destabilization in human atheromata.

Arteriosclerosis↗
PubMed1997

Severe life stress as a predictor of early disease progression in HIV infection.

OBJECTIVE: Although there is evidence that stress is associated with alterations in immunity, the role of emotional factors in the onset and course of immune-based diseases such as cancer and AIDS has not been established. This prospective study was designed to test the hypothesis that stressful life events accelerate the course of HIV disease. METHOD: Ninety-three HIV-positive homosexual men who were without clinical symptoms at the time of entry into the study were studied for up to 42 months. Subjects received comprehensive medical, neurological, neuropsychological, and psychiatric assessments every 6 months, including assessment of stressful life events during the preceding 6-month interval. Several statistical approaches were used to assess the relation between stress and disease progression. RESULTS: The time of the first disease progression was analyzed with a proportional hazard survival method, which demonstrated that the more severe the life stress experienced, the greater the risk of early HIV disease progression. Specifically, for every one severe stress per 6-month study interval, the risk of early disease progression was doubled. Among a subset of 66 subjects who had been in the study for at least 24 months, logistic regression analyses showed that higher severe life stress increased the odds of developing HIV disease progression nearly fourfold. the degree of disease progression was also predicted by severe life stress when a proportional odds logistic regression model was used for analysis. CONCLUSIONS: This report presents the first evidence from a prospective research study that severe life event stress is associated with an increased rate of early HIV disease progression.

Adult↗
PubMed1997

HSV infection of polarized epithelial cells on filter supports: implications for transport assays and protein localization.

Epithelial cell lines can be grown on filter supports and form polarized monolayers with distinct basolateral and apical plasma membrane domains. This property has been extensively used in cell biology to investigate epithelial cell function. To date, a major limitation of this approach has been the difficulty of obtaining transient gene expression in polarized epithelia. Here we present an approach to overcome this problem using gene transfer into polarized epithelial cells grown on filters using a herpes virus-based vector. Recombinant genes are inserted into a defective HSV-1 plasmid and packaged with a replication-incompetent HSV-1 helper virus into virus particles which are used to infect the polarized epithelial cells grown on filters. The transepithelial resistance of the cells is not affected by the addition of virus, and there are no detectable cytopathic effects.

Animals↗
PubMed1996

AltFGF-2, a novel ER-associated FGF-2 protein isoform: its embryonic distribution and functional analysis during neural tube development.

A novel fibroblast growth factor-2 (FGF-2) protein isoform, called altFGF-2, is expressed abundantly during chicken embryogenesis. The amino-terminal domain of the 21.5-kDa altFGF-2 protein diverges completely from the other three FGF-2 proteins due to alternative splicing of their first coding exons. Furthermore, the altFGF-2 protein, in contrast to FGF-2 proteins, is targeted predominantly to the endoplasmic reticulum. In chicken embryos, altFGF-2 and FGF-2 proteins are differentially distributed in several mesodermal structures including developing limbs and kidneys. All four FGF-2 protein isoforms are also expressed in the developing neural tube from early neural plate stages onward. In contrast to FGF-2 proteins, the altFGF-2 isoform is distributed in a dynamic, spatially restricted pattern in notochord and ventral neural tube (floor plate and motor neurons) during specification of neuronal populations. To study the possible shared or differential signaling functions of chicken altFGF-2 and FGF-2 gene products, they were ectopically expressed in the dorsal neural tube aspect of transgenic mouse embryos. Dorsal expression of altFGF-2, but not FGF-2 gene products, induced alteration of neural tube morphology in a significant fraction of mouse embryos (25%). However, no alterations of dorsoventral (d/v) neural tube polarity were detected, indicating that altFGF-2 and FGF-2 gene products either function as permissive cofactors or regulate neural tube growth without affecting establishment of its primary d/v polarity.

Alternative Splicing↗
PubMed1996

Should we embrace new drugs with open arms? Experience from a community-based, open-arm, randomized clinical trial of combination antiretroviral therapy in advanced HIV disease.

The effect of an open arm in the enrollment to a randomized clinical trial comparing zidovudine (ZDV) plus didanosine (ddI) versus ZDV plus zalcitabine (ddC) was assessed. HIV-infected individuals were eligible to participate in this protocol if they were ddI and ddC naive, had CD4 counts of 50-350/mm3, and were residents of the province of British Columbia. Participating individuals could choose between open-label ZDV/ddI, ZDV/ddC, or randomization to open-label ZDV/ddI or ZDV/ ddC. Study drugs were made available free of charge for all participants through a centralized drug distribution system. There is no other source of these drugs in the province. Primary care physicians were required to renew the patient's prescription every 2 months. Enrollment was initiated in November 1992 and was closed in March 1994 when the randomized arm of the protocol met the predetermined target sample size of 120 evaluable participants. A total of 582 patients received combination therapy in the province through this protocol: 138 (28%) enrolled in the randomized arm and 444 (76%) in the open arm. In the latter group, 320 (72%) were initially prescribed ZDV/ddI and 124 (28%) were prescribed ZDV/ddC. The enrollment rate was strikingly higher in the open arm, with 168 patients enrolled in the first 2 months compared with 138 patients enrolled in the randomized arm over 17 months. Of the 78 study physicians, 69 enrolled patients in the open arm and 23 enrolled patients in the randomized arm of the study. Experienced physicians were more likely to refer patients for randomization (p = 0.025). No statistically significant differences were observed between patients enrolled in either study arm. Our results illustrate the challenge posed to recruitment into clinical trials by the coexistence of an open arm. This is despite the noncoercive, open-label and community-based nature of our randomized protocol and the high priority given to it by a variety of local and national organizations. It is clear that an increased commitment by all interested parties will be required if randomized clinical trials are to be carried out with coexistent open arms.

Adult↗
PubMed1996

Endosome dynamics regulated by a Rho protein.

Vesicular transport is a dynamic process that requires coordinated interactions between membrane and cytoskeleton. The mechanisms and molecules integrating these interactions are unclear. A Rho protein, RhoD, might provide a molecular link between membrane traffic and the cytoskeleton. Activated RhoD causes rearrangements of the actin cytoskeleton and cell surface, and governs early endosome motility and distribution.

Actins↗
PubMed1996

Active repression of major histocompatibility complex class I genes in a human neuroblastoma cell line.

Human neuronal cells express neither major histocompatibility complex (MHC) class I RNA nor cell surface molecules but can be induced to do so by various cytokines. In the present studies, we report that expression of MHC class I in a neuroblastoma cell line, CHP-126, is actively repressed. This repression is mediated by the combined effects of a series of upstream silencer elements. Removal of the silencers reveals not only an active promoter element but also the presence of an active enhancer. Four silencers have been identified and shown to have distinct sequences, binding factors, and patterns of function. One element is located between -724 and -697 base pairs (bp) and corresponds to a silencer involved in tissue-specific regulation of class I gene expression. Three additional elements occur between -503 and -402 bp. One of these corresponds to a c-jun responsive element. Neither of the remaining elements corresponds to DNA sequences known to regulate expression of other genes. These data demonstrate that MHC class I expression normally is actively repressed in neuronal cells and suggest a model of rapid and specific triggering of class I in neuronal cells in response to infection.

Base Sequence↗
PubMed1996

In vivo analyses of interactions between SecE and SecY, core components of the Escherichia coli protein translocation machinery.

We have carried out structure-function studies on the cytoplasmic membrane protein, SecE, a component of the Escherichia coli secretion machinery. SecE, along with SecY, form a complex in the cytoplasmic membrane essential for protein translocation. By directed mutagenesis, we altered highly conserved residues of the second cytoplasmic domain (CD2) and of the COOH-terminal periplasmic region (PD2) of SecE. These mutants, as well as previously constructed mutations in the third membrane-spanning segment of SecE (MSS3), were tested for their ability to complement a secE null mutation, for their effects on protein export in vivo, and for their ability to form a stable complex with SecY. Most single mutations at the conserved positions in CD2 caused secretion defects, but had little effect on growth at 37 degrees C. Double mutations in CD2, or the introduction or removal of proline residues, affected growth and protein translocation more severely. Co-immunoprecipitations of SecE and SecY revealed that all mutant proteins, except those altered in PD2, destabilized the SecE-SecY complex. These results suggest that several regions contribute to the formation of a stable SecE-SecY complex but the elimination of a single contact point does not necessarily affect the functionality of the complex.

Amino Acid Sequence↗
PubMed1996

Insertion of the polytopic membrane protein MalF is dependent on the bacterial secretion machinery.

We examined the dependence of protein export and membrane protein insertion on SecE and SecA, two components of the secretion (Sec) apparatus of Escherichia coli. The magnitude of the secretion defect observed for signal sequence-containing proteins in cells depleted of SecE is larger and more general than that in many temperature- or cold-sensitive Sec mutants. In addition, we show that the proper insertion of the polytopic MalF protein (synthesized without a signal sequence) into the cytoplasmic membrane is also SecE-dependent. In contrast to an earlier study (McGovern, K., and Beckwith, J. (1991) J. Biol. Chem. 266, 20870-20876), the membrane insertion of MalF also is inhibited by treatment of cells with sodium azide, a potent inhibitor of SecA. Therefore, our data strongly suggest that the cytoplasmic membrane insertion of MalF is dependent on the same cellular machinery as is involved in the export of signal sequence-containing proteins. We propose that the mechanism of export from the cytoplasm is related for both signal sequence-containing and cytoplasmic membrane proteins, but hydrophobic membrane proteins such as MalF may have a higher affinity for the Sec apparatus.

ATP-Binding Cassette Transporters↗
PubMed1996

A Herpes saimiri oncogene causing peripheral T-cell lymphoma in transgenic mice.

Herpesvirus saimiri is an oncogenic virus causing rapid T-cell lymphomas in New World primates and rabbits. Deletion analysis of one strain of H saimiri has indicated an open reading frame, StpA, necessary for oncongenicity in monkeys. We have investigated the function of StpA in tumor induction by the generation of transgenic mice. Expression of two different constructs caused the development of peripheral lymphomas. The infiltrating cells were of T-cell origin, expressing mainly the CD4 phenotype and restricted sets of V beta chains. Thus, StpA is not only necessary for the oncogenicity of Herpesvirus saimiri, but is also sufficient for the induction of peripheral pleomorphic T-cell lymphomas.

Animals↗
PubMed1996

Apparent accommodation and depth of field in pseudophakia.

PURPOSE: To assess depth of field in phakic and pseudophakic eyes to explain good distance and uncorrected near visual acuity in pseudophakic eyes. SETTING: Department of Ophthalmology, University of Otago Medical School, Dunedin, New Zealand. METHODS: Depth of field was measured in pseudophakic (n = 10) and phakic (n = 10) eyes for both near and distant targets. Test conditions included cycloplegia and a constant pupillary aperture using a soft contact lens with a central artificial pupil diameter of 2.5 mm. RESULTS: There was no statistically significant difference between phakic and pseudophakic eyes for any test. Depth of field for near visual acuity was +/-0.85 diopters (D), but amplitude of legibility was +/-1.94 D. Depth of field for distance visual acuity was between 0.25 and 0.50 D in 85% of eyes. CONCLUSION: In the absence of astigmatism and disease, a pseudophakic eye with -0.75 D of myopia can expect to achieve 20/30 uncorrected distance acuity and read N5 unaided if the pupil is approximately 2.5 mm.

Accommodation, Ocular↗
PubMed1996

Prevalence and assessment of qualitative olfactory dysfunction in different age groups.

The prevalence of parosmia and phantosmia among 363 chemosensory and nasal/sinus patients was studied, as was the accuracy with which our clinical questionnaire could assess these dysfunctions. We then investigated whether patients with parosmia or phantosmia, matched for odor intensity, perform poorer on odor identification than do patients with no dysosmia. More than 40% of the study group evidenced either parosmia (18.7%) and/or phantosmia (25.6%), a finding that suggests that more attention should be paid by the medical practitioner in addressing qualitative olfactory dysfunction. Furthermore, it appears that assessment of these dysfunctions may aid in differential diagnosis, and that questionnaires can be used with reasonable validity irrespective of the patient's age. Finally, the results imply that parosmia may be reflected in a discrepancy between odor identification and detection.

Adult↗
PubMed1996

Linear growth of very young asthmatic children treated with high-dose nebulized budesonide.

The aim of this open study was to observe linear growth in young children with asthma treated with nebulized budesonide. Infants and young children (< 3 years old) with severe uncontrolled asthma were studied. They were treated with nebulized budesonide (1-4 mg day-1) and treated for at least 6 months. Height standard deviation scores (HtSDS) were measured before ("pre-measurements") immediately prior to commencing nebulized budesonide therapy (baseline) and after at least 6 months of therapy ("post-measurements"). The mean HtSDS score at pretreatment was -0.21 and at baseline had fallen further to -0.46. The mean HtSDS increased to -0.17 when the post-measurements were made (p = 0.035) after at least 6 months of nebulized budesonide therapy. Treatment with nebulized budesonide for longer than 6 months in very young children with severe asthma was not associated with reduced linear growth.

Administration, Inhalation↗
PubMed1996

Comparison of facial form in primary alveolar bone-grafted and nongrafted unilateral cleft lip and palate patients: intercenter retrospective study.

The purpose of this study was to describe and compare posttreatment craniofacial morphology in samples of complete unilateral cleft lip and palate (CUCLP) patients treated at two leading clinics: The Children's Memorial Hospital Cleft Palate Clinic, Chicago, Illinois, and the Lancaster Cleft Palate Clinic, Lancaster, Pennsylvania. These centers have well-defined treatment protocols that allow the long-term effects on craniofacial form of the following treatment regimes to be contrasted: (1) Chicago--primary alveolar bone grafting, with definitive lip repair at age 4 to 6 months and hard and soft palate repair at 6 to 12 months; and (2) Lancaster--definitive triangular-flap lip repair at 3 months of age, followed by staged surgeries of the hard and soft palates, both completed by 18 months of age, but without primary alveolar bone grafting. Although the Lancaster center now performs secondary alveolar bone grafting, the majority of the patients studied here were treated before this procedure became part of their protocol. Patients were eligible for inclusion if they had no other congenital anomalies and no previous orthodontic treatment. A sample of 43 (24 male, 19 female) CUCLP patients was obtained from the Chicago Center, each of which was then matched to a nongrafted Lancaster CUCLP patient. The matching criteria were age, sex, and sella-nasion distance (to control, at least in part, for size differences). Lateral cephalometric radiographs of these 86 CUCLP patients were traced, digitized, and analyzed. Additionally, all linear data were adjusted to a standard magnification of 8% because the cephalograms from each center featured different enlargements. The Chicago and Lancaster samples had mean posttreatment ages of 10.32 years (SD = 1.96) and 10.40 years (SD = 2.18), respectively. The grafted Chicago group had faces that were on average less maxillary protrusive compared with the nongrafted Lancaster sample; it appeared, however, that the mandible compensated for the maxillary position by downward and backward rotation. As a result, a similar maxillomandibular relationship was noted in both groups, although, in the Chicago group, the lower anterior facial height increased.

Alveolar Process↗