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Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1998

Assembly of lampbrush chromosomes from sperm chromatin.

We have examined the behavior of demembranated sperm heads when injected into the germinal vesicle (GV) of amphibian oocytes. Xenopus sperm heads injected into Xenopus GVs swelled immediately and within hours began to stain with an antibody against RNA polymerase II (Pol II). Over time each sperm head became a loose mass of chromosome-like threads, which by 24-48 h resolved into individually recognizable lampbrush chromosomes (LBCs). Although LBCs derived from sperm are unreplicated single chromatids, their morphology and immunofluorescent staining properties were strikingly similar to those of the endogenous lampbrush bivalents. They displayed typical transcriptionally active loops extending from an axis of condensed chromomeres, as well as locus-specific "landmarks. " Experiments with [3H]GTP and actinomycin D demonstrated that transcription was not necessary for the initial swelling of the sperm heads and acquisition of Pol II but was required for maintenance of the lampbrush loops. Splicing was not required at any stage during formation of sperm LBCs. When Xenopus sperm heads were injected into GVs of the newt Notophthalmus, the resulting sperm LBCs displayed very long loops with pronounced Pol II axes, like those of the endogenous newt LBCs; as expected, they stained with antibodies against newt-specific proteins. Other heterologous injections, including sperm heads of the frog Rana pipiens and the zebrafish Danio rerio in Xenopus GVs, confirm that LBCs can be derived from taxonomically distant organisms. The GV system should help identify both cis- and trans-acting factors needed to convert condensed chromatin into transcriptionally active LBCs. It may also be useful in producing cytologically analyzable chromosomes from organisms whose oocytes do not go through a typical lampbrush phase or cannot be manipulated by current techniques.

Animals↗
PubMed1998

Measuring line-related bacteraemia in intensive care patients.

All patients with an intravascular device in the intensive care units at Prince of Wales and Prince Henry Hospitals between July and September 1995 were followed for the development of line-related bacteraemia per 1000 line days. Cases of sepsis related to an intravascular device were identified using a case definition which incorporated clinical and laboratory parameters. Data were collected prospectively for the dates of insertion and removal of devices for 188 lines inserted in 69 patients. The majority (90%) of lines had both date of insertion and removal documented allowing the calculation of the rate of primary bacteraemia over 832 at-risk line days. Multiple concurrent lines were more common (88.4%) than single lines, with one central and one or two peripheral lines being the most common (42.3%) combination. Five cases of bacteraemia were diagnosed clinically and confirmed microbiologically. The incidence density of primary bacteraemia was 6.0 per 1000 line days (CI 95% 5.7-6.3).

APACHE↗
PubMed1998

Importance of glutamine metabolism in murine macrophages and human monocytes to L-arginine biosynthesis and rates of nitrite or urea production.

1. The intermediates of biochemical cycles are commonly utilized for biosynthetic processes; thus at least one intermediate must be replenished de novo to provide constant flux through the cycle. The utilization of L-arginine for NO synthesis in macrophages may thus reduce the concentration of intermediates of the urea cycle. It is possible that a glutamine-utilizing pathway exists in mononuclear phagocytes that may connect with the urea cycle.2. In this paper we report that mouse peritoneal resident and Bacillus Calmette-Guerin (BCG)-activated macrophages and human monocytes are capable of utilizing glutamine at high rates, contain sufficient activity of the enzymes required to convert glutamine to citrulline (and subsequently citrulline to arginine) to account for observed rates of nitrite synthesis in the absence of extracellular L-arginine, and will release nitrite when exposed to intermediates of the proposed glutamine-->arginine pathway.3. The rate of nitrite production (in the absence of extracellular arginine) was reduced by culturing macrophages or monocytes in the presence of the glutaminase inhibitor 6-diazo 5-oxo norleucine.4. The rate and extent of arginase secretion, glutamine utilization, nitrite production (basal and lipopolysaccharide-stimulated) and phosphate-dependent glutaminase activity from BCG-activated macrophages was increased compared with resident cells.5. We suggest that the elevated arginase secretion rates in activated macrophages would effectively increase the intracellular concentration of arginine available for conversion to NO via inducible nitric oxide synthase, the expression of which is known to increase on activation of macrophages or monocytes. Additionally, the rate of L-arginine biosynthesis from glutamine may be increased on immunostimulation of the macrophage.

Animals↗
PubMed1997

Rapid clinical evaluation of anosmia. The alcohol sniff test.

BACKGROUND: Smell impairment affects 1% to 2% of Americans and leads to frequent physician visits. Olfactory testing is available in chemosensory centers, but not as part of a routine cranial nerve examination. The alcohol sniff test (AST), which uses the standard 70% isopropyl alcohol pad, was developed as a quick, reliable measure of olfactory function. METHODS: Sixty-four patients and 36 healthy control subjects (N = 100) were tested with the AST and with a standard butanol threshold test. RESULTS: The AST reliably, consistently, and correctly measured olfactory function. CONCLUSIONS: The AST is a rapid, reliable olfactory test that can be used for screening olfactory function and should be incorporated in the routine cranial nerve examination.

1-Propanol↗
PubMed1997

Olfactory event-related potentials: older males demonstrate the greatest deficits.

Olfactory event-related potentials (OERPs) were recorded monopolarly at the Fz, Cz, and Pz electrode sites in 16 young adults (8M/8F) and 16 older adults (8M/8F) with inter-stimulus intervals (ISI) of 45, 60 and 90 s using amyl acetate as the odorant stimulus. N1, P2, and N2 peak amplitudes and latencies were measured. Young participants demonstrated significantly shorter peak latencies than older participants. Older males demonstrated significantly smaller peak amplitudes than the other participant groups. Peak amplitudes also increased with longer ISIs for older males. The OERP is compared to traditional olfactory psychophysical testing.

Adult↗
PubMed1997

Odor learning, recall, and recognition memory in young and elderly adults.

use of an odor learning test and the California Verbal Learning Test in young and elderly adults enabled comparison of age-related effects on recall and recognition memory. Assessment of odor identification further enabled study of which odor function (recall, identification, recognition) is most affected by aging, the odor functions' interrelationships, and predictors of odor recall. Results suggested that both recall and recognition were significantly affected by aging and that the odor-recall decline cannot simply be referred to poor identification. Very similar age-related effect sizes were found for the 3 types of odor functions. Finally, the combined ability to encode, store, and retrieve odors appears to predict overall recall performance (including its identification component) better than do identification and recognition.

Adolescent↗
PubMed1997

Rate of seasonal spread of respiratory syncytial virus in a pediatric hospital.

The rate of nosocomial respiratory syncytial virus (RSV) infection was measured in a large pediatric hospital using an incidence density method. The at-risk days for nosocomial RSV were summed during a defined winter period in which there were 54 admissions with community-acquired RSV infection giving a rate of 2.9 cases per 1,000 at-risk days (95% confidence interval, 0.3-5.4 per 1,000).

Community-Acquired Infections↗
PubMed1997

Chronobiology of nasal chemosensitivity: do odor or trigeminal pain thresholds follow a circadian rhythm?

Odor and trigeminal pain thresholds were studied four times each at 24:00, 04:00, 08:00, 12:00, 16:00 and 20:00 h in randomized order on different days in five healthy male volunteers. No circadian rhythm of olfactory or trigeminal thresholds were observed. However, the variability of odor, but not pain thresholds, increased from 04:00 h (thresholds between 0.4 and 1.2 p.p.m.) to 16:00 h (thresholds between 0.1 and 2 p.p.m.). It is hypothesized that environmental influences contribute to this increase in variance.

Adult↗
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↗