PubMed Health⌕ Search

Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 109 records · Page 6Linked to original sources
PubMed1998

EEA1 links PI(3)K function to Rab5 regulation of endosome fusion.

GTPases and lipid kinases regulate membrane traffic along the endocytic pathway by mechanisms that are not completely understood. Fusion between early endosomes requires phosphatidylinositol-3-OH kinase (PI(3)K) activity as well as the small GTPase Rab5. Excess Rab5-GTP complex restores endosome fusion when PI(3)K is inhibited. Here we identify the early-endosomal autoantigen EEA1 which binds the PI(3)K product phosphatidylinositol-3-phosphate, as a new Rab5 effector that is required for endosome fusion. The association of EEA1 with the endosomal membrane requires Rab5-GTP and PI(3)K activity, and excess Rab5-GTP stabilizes the membrane association of EEA1 even when PI(3)K is inhibited. The identification of EEA1 as a direct Rab5 effector provides a molecular link between PI(3)K and Rab5, and its restricted distribution to early endosomes indicates that EEA1 may confer directionality to Rab5-dependent endocytic transport.

Androstadienes↗
PubMed1998

Rab17 regulates membrane trafficking through apical recycling endosomes in polarized epithelial cells.

A key feature of polarized epithelial cells is the ability to maintain the specific biochemical composition of the apical and basolateral plasma membrane domains while selectively allowing transport of proteins and lipids from one pole to the opposite by transcytosis. The small GTPase, rab17, a member of the rab family of regulators of intracellular transport, is specifically induced during cell polarization in the developing kidney. We here examined its intracellular distribution and function in both nonpolarized and polarized cells. By confocal immunofluorescence microscopy, rab17 colocalized with internalized transferrin in the perinuclear recycling endosome of BHK-21 cells. In polarized Eph4 cells, rab17 associated with the apical recycling endosome that has been implicated in recycling and transcytosis. The localization of rab17, therefore, strengthens the proposed homology between this compartment and the recycling endosome of nonpolarized cells. Basolateral to apical transport of two membrane-bound markers, the transferrin receptor and the FcLR 5-27 chimeric receptor, was specifically increased in Eph4 cells expressing rab17 mutants defective in either GTP binding or hydrolysis. Furthermore, the mutant proteins stimulated apical recycling of FcLR 5-27. These results support a role for rab17 in regulating traffic through the apical recycling endosome, suggesting a function in polarized sorting in epithelial cells.

Amino Acid Sequence↗
PubMed1998

Effects of nasal-airway volume and body temperature on intranasal chemosensitivity.

Interrelations between intranasal detection sensitivity for odor (H2S) and pain (CO2), nasal-airway volume (acoustic rhinometry), and body temperature were studied in young, healthy men across the diurnal cycle. The results showed a weak but statistically significant negative correlation between nasal volume and odor threshold and a weak but positive correlation between body temperature and odor threshold.

Adult↗
PubMed1998

Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro.

Mononuclear phagocytes play an important role in atherosclerosis and its sequela plaque rupture in part by their secretion of matrix metalloproteinases (MMPs), including MMP-9. Peroxisomal proliferator-activated receptor gamma (PPARgamma), a transcription factor in the nuclear receptor superfamily, regulates gene expression in response to various activators, including 15-deoxy-delta12,14-prostaglandin J2 and the antidiabetic agent troglitazone. The role of PPARgamma in human atherosclerosis is unexplored. We report here that monocytes/macrophages in human atherosclerotic lesions (n = 12) express immunostainable PPARgamma. Normal artery specimens (n = 6) reveal minimal immunoreactive PPARgamma. Human monocytes and monocyte-derived macrophages cultured for 6 days in 5% human serum expressed PPARgamma mRNA and protein by reverse transcription-polymerase chain reaction and Western blotting, respectively. In addition, PPARgamma mRNA expression in U937 cells increased during phorbol 12-myristate 13 acetate-induced differentiation. Stimulation of PPARgamma with troglitazone or 15-deoxy-delta12,14-prostaglandin J2 in human monocyte-derived macrophages inhibited MMP-9 gelatinolytic activity in a concentration-dependent fashion as revealed by zymography. This inhibition correlates with decreased MMP-9 secretion as determined by Western blotting. Thus, PPARgamma is present in macrophages in human atherosclerotic lesions and may regulate expression and activity of MMP-9, an enzyme implicated in plaque rupture. PPARgamma is likely to be an important regulator of monocyte/macrophage function with relevance for human atherosclerotic disease.

Arteriosclerosis↗
PubMed1998

Adult susceptibility to varicella in the tropics is a rural phenomenon due to the lack of previous exposure.

In the industrialized countries of the West, varicella is largely a childhood disease, whereas reports from tropical countries indicate a significant incidence of varicella among adults. High ambient temperature, epidemiologic interference from other viruses, and race have been blamed. We tested our hypothesis that less exposure to varicella-zoster virus (VZV) during childhood in rural areas accounts for the reported greater frequency of varicella in adults in tropical climates by comparing rates of VZV seropositivity among urban and rural adult Bengalee populations living in identical climatic conditions in India. Only 5 (3.4%) of 153 urban adults were seronegative compared with 74 (31.1%) of 246 rural adults. Ninety-six percent of urban adults were immune by the age of 25, compared with 42% in the rural group. The results suggest that higher adult susceptibility to varicella is seen only in rural areas of the Tropics and is due to reduced transmission of VZV.

Adult↗
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↗