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Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 163 records · Page 9Linked to original sources
PubMed1994

Continuous measurements of changes in pulmonary capillary surface area with 201Tl infusions.

The impact of physiological and pathological processes on metabolism and transport of a variety of substances traversing the pulmonary vasculature depends in part on the capillary surface area available for exchange, and a reliable method for detecting changes in this parameter is needed. In this study, a continuous-infusion approach was used to investigate the response of the pulmonary capillary surface area to increases in flow and left atrial pressure. Isolated rat lungs were perfused with an acellular perfusion solution containing 125I-labeled albumin (an intravascular indicator) and 201Tl, a K+ analogue which is concentrated within lung cells. The extraction of 201Tl from the perfusate was 61% greater at low flow (8.5 ml/min) than at high flow (26 ml/min), and rapid changes in extraction were observed when flow was altered. In contrast, the permeability-surface area product was 76% greater when lungs were perfused at high flow than at low flow, suggesting comparable increases in pulmonary capillary surface area in these zone 2 lungs (airway pressure = 5 cmH2O, left atrial pressure < 0 cmH2O). In a second group of experiments, increases in left atrial pressure to 14 cmH2O (zone 3 lungs) at a constant flow of 8.5 ml/min increased the permeability-surface area product by only 18% despite increases in average intravascular pressure that were at least as high as those associated with high perfusion rates. 201Tl infusions provide a useful method for detecting and quantifying changes in pulmonary capillary surface area.

Animals↗
PubMed1994

Mood disorders in HIV infection: prevalence and risk factors in a nonepicenter of the AIDS epidemic.

OBJECTIVE: The authors studied the lifetime, initial cross-sectional, and 6-month follow-up prevalence of mood disorders in asymptomatic HIV-infected and uninfected homosexual men who lived in an area with a low prevalence of HIV. They also determined the relationship between current major depression and potential depression risk factors. METHOD: Subjects included 98 asymptomatic HIV-infected and 71 uninfected homosexual men. Subjects underwent extensive clinical, psychiatric, neuropsychological, and laboratory evaluations. RESULTS: Similar proportions of HIV-infected and uninfected subjects reported a lifetime (29% and 45%, respectively), an initial current (8% and 3%), and a 6-month follow-up (9% and 11%) history of major depressive disorder. Anxiety disorders were less common, with similar proportions of HIV-infected and uninfected subjects reporting a lifetime (7% and 13%, respectively), an initial current (3% and 7%), and a 6-month follow-up (2% and 5%) history of anxiety disorders. There were no differences in the severity of mood symptoms between HIV-infected and uninfected subjects. Current major depression at initial visit was significantly associated with lifetime history of major depression but not with neuropsychological function or vitamin B12 level. CONCLUSIONS: These findings are in agreement with previous studies of areas with a high prevalence of HIV. However, the proportion of subjects with mood disorders is high compared with general population studies. Both HIV-infected and uninfected homosexual men may be at high risk for major depression, especially if they have a past history of depression. Moreover, in the asymptomatic stage of HIV infection, major depression does not appear to be secondary to HIV central nervous system effects or low vitamin B12 levels.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cloning and subcellular localization of novel rab proteins reveals polarized and cell type-specific expression.

Small GTPases of the rab subfamily are specific regulators of vesicular transport. The intracellular localization of these proteins has been mostly investigated in cultured cells where they have been found associated with distinct compartments of the exocytic and endocytic pathways. Using a PCR-based cloning approach we have recently identified several novel rab proteins, extending the total number of this family to more than 30 members. Here, we have investigated the mRNA expression in different tissues and the intracellular localization in organ cryosections of two rab proteins, rab18 and rab20. Both northern blot analysis and confocal immunofluorescence microscopy demonstrated that these proteins are expressed in a tissue- and cell type-dependent manner. Despite their presence in non-polarized cells and polarized cells, both proteins are highly expressed on the apical side of kidney tubule epithelial cells. Electron microscopic studies revealed that rab18 and rab20 are located in apical dense tubules, endocytic structures underlying the apical plasma membrane, suggesting that they play a role in apical endocytosis/recycling. In intestinal epithelial cells as well, both proteins were localized apically, but, in addition, rab18 was found associated with the basolateral domain, suggesting that this protein is not restricted to the apical transport machinery of polarized epithelial cells. The results demonstrate that, depending on the epithelial cell type, rab proteins that are also expressed in non-polarized cells may be enriched in one or both surface domains. Together with the observed tissue- and cell type-dependent variation in the expression of the rab proteins, this suggests that the large number of mammalian rab proteins might reflect the specific requirements in the organization of membrane traffic encountered by different cell types.

Amino Acid Sequence↗
PubMed1994

Epithelial tumours induced by a herpesvirus oncogene in transgenic mice.

To investigate the role of herpesviral genes in tumourigenesis, transgenic mice were generated expressing STP-C, a transformation associated protein of the lymphoma inducing herpesvirus saimiri. Epithelial tumours developed in the salivary gland, pancreas, thymus and liver of transgenic mice within the first weeks of life. Thus, the target cells for tumour formation in the transgenic mice were surprisingly different from those of the herpesvirus from which the oncogene was derived. Our results identify STP-C as a herpesvirus oncogene sufficient for tumour induction without the cooperation of other viral gene products. Furthermore, the results demonstrate pleiotropic transforming capabilities of the STP-C oncogene and suggest that the specificity of lymphoma induction by the virus is determined by factors other than the oncogene itself.

Animals↗
PubMed1993

Generation and pathogenicity of an NB-tropic SL3-3 murine leukemia virus.

A 428-base pair region of the gag gene of a molecular clone of the SL3-3 murine leukemia virus (MuLV) was replaced with allelic sequences that contain the NB-tropic determinants of the Moloney MuLV. SL3-3NB, the ecotropic virus derived from this modified clone, rapidly induced T-cell lymphoblastic lymphomas in the Fv-1n mouse strains CWD and NIH Swiss and the Fv-1b strain, B10.Br. By Southern blot assay, each of the CWD tumors and all but one of the B10.Br tumors that were tested contained recombinant proviruses. The envelope genes of the B10.Br recombinant viruses retained the SL3-3NB 5' p15E (TM) gene sequences (type I env), whereas the CWD recombinants did not (type II env). The production of type I env recombinants by B10.Br mice is a characteristic that is shared with other mouse strains that express the H-2k haplotype. The results indicate that the inserted Moloney virus gag sequences conferred NB-tropism to SL3-3NB and did not interfere with the expression of SL3-3 pathogenic determinants or the formation of recombinant viruses.

Animals↗
PubMed1993

Effects of hyperglycemia on memory and hormone levels in dementia of the Alzheimer type: a longitudinal study.

The effect of hyperglycemia on hormone levels, metabolite levels, and memory performance was examined in 22 subjects with very mild and mild probable dementia of the Alzheimer type (DAT) and in 12 normal elderly adults. Subjects were tested in 3 plasma glucose conditions (fasting baseline, 175 mg/dl, and 225 mg/dl) at initial and 18-month follow-up sessions. Initially, adults with very mild DAT showed memory facilitation and elevations in plasma insulin in the 225-mg/dl glucose condition relative to baseline. At follow-up, very mild DAT patients whose dementia had progressed showed significant decreases in insulin and hyperglycemic memory facilitation. Changes in basal insulin and cortisol levels over time were correlated with memory changes for DAT subjects. These results suggest that glucoregulatory abnormalities may contribute to the pathophysiology of DAT.

Aged↗
PubMed1993

Nutrition and chemosensory perception in the elderly.

The elderly person's perception of foods and food flavor is affected by age-associated changes in the chemical senses (taste, smell, and trigeminal sensation). Both classic and modern psychophysical techniques have been applied to achieve some understanding of these changes. Taste threshold sensitivity declines with age; however, the magnitude of the decline and the degree to which taste qualities are differentially affected remains to be understood. Suprathreshold taste intensity perception is affected by age, but there is a differential effect of taste quality. Experiments with blended foods have indicated that both olfactory and taste deficits contribute to older people's difficulty with food identification. Experiments assessing threshold sensitivity, suprathreshold intensity, and suprathreshold identification have all demonstrated significant impairment in olfaction in old age. In fact, these effects are far greater than in the taste system. Patients with Alzheimer's disease show even greater olfactory deficits than normal elderly and the effect is related to the degree of dementia. We have ruled out nasal disease in these patients as the primary causes of olfactory insensitivity, because significant impairment remains when the influence of nasal airflow and nasal cytology has been removed statistically. Both normal elderly and patients with Alzheimer's disease show impairment in odor memory. Sensitivity to, familiarity with, and identifiability of the odors all play a role in odor memory performance. Flavor preference also changes over the lifespan. Older subjects, for instance, rate high concentration of sugar and salt as pleasanter than young subjects do. Multiple influences contribute to this phenomenon. Elderly persons and those of lower nutritional status have shown preferences for higher concentrations of casein hydrolysate than young persons and those of higher nutritional status, suggesting that dietary preference can be related to chemosensory cues. There are significant age-associated changes in chemosensory perception that have the potential to interact with dietary selection and nutrition in the elderly. A better understanding of these phenomena may promote health and well-being in the elderly.

Aged↗
PubMed1993

Snurposomes and coiled bodies.

In the GV of amphibian oocytes, the splicing snRNPs (U1, U2, U4, U5, and U6) occur on most of the lampbrush chromosome loops in association with the nascent transcripts. They also occur in thousands of small extrachromosomal bodies (1-4 microns in diameter) designated B snurposomes. U7 snRNA, which is involved in processing the 3' end of histone pre-mRNAs, occurs in a few dozen extrachromosomal bodies (1-20 microns in diameter) called C snurposomes. C snurposomes often have B snurposomes attached to their surface and B-like inclusions; these compound structures are known as spheres or sphere organelles. One or two sphere organelles are attached to the lampbrush chromosomes at the histone gene loci. Two snRNAs (or snoRNAs) known to be involved in pre-rRNA processing (U3 and U8) occur in the 1000 or so extrachromosomal nucleoli of the GV. We looked for a snurposome that might contain U3 and U8 but not rDNA or rRNA. We were unable to find such a snurposome, but we did identify a hitherto unrecognized population of minute nucleoli in the size range of B snurposomes. Prenucleolar bodies in telophase/early interphase nuclei meet the definition of a pre-rRNA snurposome in that they contain U3 snoRNA and fibrillarin (and probably other processing components) but lack rDNA and do not synthesize rRNA. The structures previously identified as prenucleolar bodies in pronuclei formed in vitro in Xenopus egg extracts share many components with coiled bodies from HeLa nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Reversible inhibition of urea exchange in rat hepatocytes.

Urea exchange is enhanced in renal collecting duct cells and erythrocytes by transporters which can be inhibited by phloretin and urea analogs such as thiourea. In this study, evidence for a comparable transporter was found in rat livers perfused with solutions which contained no red cells and in suspensions of hepatocytes. Bolus injections containing 125I-albumin (intravascular indicator), 99mTc-DTPA (extracellular indicator), 3HOH (water indicator), and [14C]urea were administered into the portal vein and fluid was collected from the hepatic vein. Under control conditions, [14C]urea and 3HOH emerged from the hepatic vein at nearly the same rate. However when the perfusate contained 2.5 mM phloretin (equivalent to 0.058 mM phloretin not bound to albumin), the amount of [14C]urea which had been recovered in the hepatic venous outflow by the time of peak 125I-albumin concentrations exceeded 3HOH recovery by a factor of 2.31 +/- 0.23 (n = 7). When the perfusate contained 200 mM thiourea, the comparable recovery of [14C]urea from the hepatic veins exceeded that of 3HOH by a factor of 3.48 +/- 0.44 (n = 7). These effects were at least partially reversible and suggested inhibition of urea transporters in hepatocytes. This conclusion was supported by studies of unloading of [14C]urea from hepatocytes which were exposed to unlabeled solutions: in the presence of phloretin, the amount of [14C]urea remaining within hepatocytes at 4 s was approximately twice that remaining in hepatocytes which had not been exposed to phloretin. Rapid transport of urea out of hepatocytes may increase urea synthesis and minimize cellular swelling due to urea accumulation.

Animals↗
PubMed1993

The community's tolerance of the mentally ill.

A survey of attitudes to mental illness was conducted in a quota sample of about 2000 subjects in Malvern and Bromsgrove. Factor analysis showed three main components - benevolence, authoritarianism, and fear of the mentally ill. Residents of Bromsgrove, which is served by a traditional mental hospital, were slightly more tolerant than those living in Malvern, which has a community-based service, and has seen the closure of two mental hospitals in its vicinity during the last 10 years. The main demographic determinants of tolerance are age, education, occupation, and acquaintance with the mentally ill.

Adolescent↗
PubMed1993

A comparison of responses to the mentally ill in two communities.

Vignettes representing mentally ill people were presented to about 2000 randomly selected residents in Bromsgrove, served by a mental hospital, and Malvern, served by a community-based psychiatric service. They were asked about the likely cause of the condition, what action they would take, and what agencies were most likely to help. In Malvern, residents seemed more enterprising in involving various agencies and more tolerant. It is possible to derive simple 'action scores' as an indicator of such tolerance. Although there were significant demographic differences between subgroups, overall identification of vignette subjects as mentally ill was surprisingly low, and so was knowledge both of community psychiatric nurses as an agency, and of the location of dispersed treatment facilities in both areas.

Adolescent↗
PubMed1993

The interaction of the tyrosine kinase pp60src with membrane and cytoskeletal components.

To study the mechanism of oncogenic transformation we have investigated the association of pp60v-src with the cytoskeleton using a variety of mutants. Transformation is associated with the interaction of pp60v-src with the cytoskeleton, specifically in adhesion plaques. Biochemical analysis has shown a correlation between tyrosine-specific phosphorylation of the fibronectin receptor and the loss of surface-bound fibronectin, but no such correlation with phosphorylation of vinculin or talin. The role of the nontransforming protooncogene product pp60c-src was studied in platelets, which express large amounts of this protein. In resting platelets pp60c-src was soluble in detergent-containing buffers, however it became associated with the cytoskeleton, but not the membrane skeleton, after platelet activation. This association was inhibited by EDTA or RGDS peptides and was therefore dependent on occupancy of a platelet integrin, gpIIb/IIIa. The role of pp60c-src-associated tyrosine phosphorylation in platelet activation was also investigated. Inhibitors of tyrosine phosphorylation inhibited integrin-dependent platelet aggregation and second messenger production, indicating a close linkage between matrix receptor occupancy, pp60c-src association with the cytoskeleton and platelet function.

Animals↗
PubMed1993

Psychosocial predictors of high-risk sexual behavior among HIV-negative homosexual men.

Despite general awareness that human immunodeficiency virus (HIV) is transmitted sexually, people continue to engage in high-risk behavior. As part of a larger HIV project, the Coping in Health and Illness Project (CHIP), we studied the association of psychosocial factors with sexual risk taking behaviors in 53 HIV-negative gay men residing in a HIV non-epicenter. Risk behavior was measured on a 3-point scale, taking into account condom use, number of sexual partners, and type of sexual activity. Independent variables included mood, coping, history of substance dependence, social support, and acceptance of sexual orientation. Sixty percent of the subjects practiced lower-risk, 17.3% practiced moderate-risk, and 23.1% practiced high-risk behavior. We found that risk behavior was positively correlated with optimism (Life Orientation Test) (OR = 2.7; 95% CI = 1.3-5.5), anger (POMS) (OR = 2.6; 95% CI = 1.2-5.7), and negatively related to emotional control (Courtauld) (OR = 0.5; 95% CI = 0.3-1.0), and gay self-acceptance (OR = 0.35; 95% CI = 0.2-0.8). Further study is needed to determine if sexual risk-taking behavior in HIV-negative gay men will be reduced by enhancing gay self-esteem, increased understanding and adaptive use of anger, and modifying overly optimistic attitudes to increase realism.

Adaptation, Psychological↗
PubMed1992

Sarcolipin, the "proteolipid" of skeletal muscle sarcoplasmic reticulum, is a unique, amphipathic, 31-residue peptide.

The sarcoplasmic reticulum of rabbit skeletal muscle contains a small "proteolipid," i.e., a protein which is soluble in acidic CHCl3/CH3OH. We propose the name sarcolipin for this small protein, to signify its lipid-like solubility and association with the sarcoplasmic reticulum. We have determined the following amino acid sequence for sarcolipin, using protein chemistry methods: M E R S T R E L C L N F T V V L I T V I L I W L L V R S Y Q Y. This 31-residue sequence includes a 19-residue hydrophobic segment which probably spans the sarcoplasmic reticulum membrane. The molecular weight calculated from the sequence, 3733, agrees with that measured by fast atom bombardment mass spectrometry, showing that sarcolipin contains no attached fatty acyl or other prosthetic groups.

Amino Acid Sequence↗
PubMed1992

5S rRNA-encoding genes of the marsupial frog Gastrotheca riobambae.

The major 5S rRNA gene repeat of the marsupial frog, Gastrotheca riobambae, is 1052 bp in length. It contains a 5S rRNA gene similar to the Xenopus laevis somatic gene, two spacer regions, and a pseudogene. The G. riobambae haploid genome contains about 500 copies of this predominant repeat. This relatively low number of 5S rRNA genes is associated with a limited amplification of the 18S, 5.8S and 28S rRNA genes in oocytes and with a slow rate of early development.

Animals↗