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Biomedical subjects

R Murphy

Publications and source records attributed to R Murphy.

At least 109 records · Page 6Linked to original sources

Effects of neonatal thymectomy on the densities of nicotinic cholinergic receptors in skeletal muscle and brain.

It has been suggested that the thymic polypeptide thymopoietin interacts with skeletal muscle nicotinic acetylcholine receptors (nAChRs) and brain nicotinic receptors labeled by alpha-bungarotoxin (alpha-BuTX). In this study, the effects of neonatal thymectomy on the density of skeletal muscle nAChRs and the density of brain alpha-BuTX binding sites at 7 and 45 days postnatal were investigated. In addition, the densities of receptors in the skeletal muscle and brain of the athymic nu/nu mouse at 42 days postnatal were measured. We found little evidence that the absence of the thymus alters the density of nicotinic receptors in either skeletal muscle or brain.

Aging↗

Effects of potassium-aspartate salt administration on glycogen use in the rat during a swimming stress.

The ergogenic effect of aspartate salts on performance during prolonged exercise is still controversial. Potential mechanisms of the suggested ergogenic effect of aspartate on exercise performance are a sparing of muscle glycogen stores or its faster resynthesis during exercise. The purpose of this study was to determine whether aspartate causes a sparing of muscle glycogen during exercise. Six groups of rats were studied: one group received a single injection of aspartate (1 g.kg-1, IP) and was then sacrificed at rest, a second group of aspartate-treated rats was sacrificed after a 60-min swim. The third and fourth groups were given an injection of physiological saline and then sacrificed respectively at rest and after a 60-min swim. The fifth and sixth groups were given an aspartate or a saline injection and then sacrificed after swimming to exhaustion. The exhaustion times after saline (178.9 +/- 38.2 min) and aspartate (174.4 +/- 45.2 min) were not significantly different. Results did not confirm an ergogenic effect of a single dose of aspartate on swimming endurance in the rat. Aspartate-treated rats had a significantly lower plasma FFA concentration after swimming to exhaustion when compared to control rats (respectively, 0.70 +/- 0.25 vs. 1.16 +/- 0.45 mM). Also, the results of the present study do not support the hypothesis of a sparing of muscle or liver glycogen with aspartate, because a similar content of glycogen remained in the muscles and liver of control rats after a 60-min swim or after swimming to exhaustion.

Ammonia↗

A case of ocular ischaemic syndrome in a young insulin dependent diabetic male.

It is well known that diabetic patients are at an increased risk of the earlier development of significant atherosclerotic disease. We wish to report the case of a young insulin-dependent diabetic with an 18 months history of rapidly progressing 'diabetic' retinopathy who presented with right-sided weakness and was found to have severe carotid artery disease. We suggest that the sudden proliferation in his retinopathy was due to retinal ischaemia secondary to the carotid artery stenosis and we wish to present this as a case of ocular ischaemic syndrome in a young diabetic patient.

Adult↗

Quantification of human immunodeficiency virus type 1 tat mRNA as a marker for assessing the efficacy of antiretroviral therapy.

To evaluate the use of human immunodeficiency virus type 1 (HIV-1) tat mRNA quantification as a marker for antiretroviral therapy, 10 zidovudine-naive, p24 antibody-positive subjects (Centers for Disease Control classes III and IV) were studied at the start of zidovudine treatment. HIV-1 proviral DNA content and tat mRNA levels were monitored for 20 weeks from the initiation of therapy. Levels of tat mRNA were quantified using an engineered tat cRNA internal control under conditions of linear amplification. Proviral DNA levels increased in 2 patients and decreased in 8 during 20 weeks of therapy. In each case, tat mRNA levels exhibited similar but much more pronounced changes. Results indicate that quantitative measurement of tat mRNA levels is extremely useful for monitoring antiretroviral therapy.

DNA, Viral↗

Concurrent use of ganciclovir and foscarnet to treat cytomegalovirus infection in AIDS patients.

Ten patients with AIDS and progressive cytomegalovirus disease were treated with ganciclovir and foscarnet concurrently. The patients had received ganciclovir and foscarnet monotherapy a median of 330 days before receiving combination therapy for a median of 80 days. Nine of the 10 patients responded to the combination. No electrolyte abnormalities were noted during combination therapy, but rates of neutropenia (relative rate, combination vs. ganciclovir, 1.99; P = .229) and thrombocytopenia (relative rate, combination vs. ganciclovir, 1.53; P = .616) were higher with combination therapy than with either drug alone. The relative rate of anemia was significantly increased with combination therapy compared with monotherapy (relative rate, combination vs. ganciclovir, 2.69; P = .025). These data suggest that combination ganciclovir and foscarnet therapy after failure of either alone appears to be as effective as standard therapy with single agents. The rate of anemia with combination therapy was significantly greater than either agent alone, but no significant difference was noted among the other parameters of toxicity studied.

AIDS-Related Opportunistic Infections↗

Socioeconomic status and coronary heart disease risk factor trends. The Minnesota Heart Survey.

BACKGROUND: Socioeconomic status (SES) indicators including education, income, and occupation are associated with coronary heart disease (CHD) risk factors, morbidity, and mortality. In most industrialized nations, individuals with less education, lower income, and blue collar occupations have the highest CHD rates. It is suggested by some that these differences by SES are increasing even as age-adjusted CHD mortality declines. METHODS AND RESULTS: The Minnesota Heart Survey includes measurement of CHD risk factors and behaviors in population-based samples of Minneapolis-St. Paul adults aged 25 to 74 years in 1980 to 1982 (N = 3243) and 1985 to 1987 (N = 4538). Education was significantly and inversely related to blood pressure, cigarette smoking, body mass index, and a summary risk score for both men and women. Serum cholesterol was inversely related to education in women but not in men. Education was positively associated with leisure physical activity and health knowledge. Associations with household income were less consistent in magnitude and direction. Risk characteristics improved significantly between the 1980 to 1982 and 1985 to 1987 surveys. These changes were similar across education and household income levels. CONCLUSIONS: Improvement in CHD risk factors over time unrelated to education or income suggests that population-wide factors such as improved health knowledge, availability of healthy food items, hypertension treatment, and restrictions on cigarette smoking are operating beneficially in all SES groups. Although the SES gradient in risk factors is not increasing, it remains substantial and indicates directions for future prevention efforts.

Adult↗

Migration stimulating factor (MSF): its structure, mode of action and possible function in health and disease.

We have previously reported that (a) fetal fibroblasts migrate into 3-dimensional collagen matrices to a significantly greater extent that do adult cells, (b) this difference in migratory behaviour results from the secretion by fetal fibroblasts of a "migration stimulating factor" (MSF), and (c) adult fibroblasts retain responsiveness to MSF, this providing the basis of a bioassay for monitoring factor activity. Using a recently modified purification protocol, MSF isolated from fetal fibroblast conditioned medium elutes as a single activity peak in the penultimate Mono Q anion exchange chromatography step. Analysis of this material by SDS-PAGE indicates that it consists of three proteins, one with an apparent molecular mass of 119 kDa and a doublet with molecular masses of approximately 43 and 33 kDa, respectively. Our data suggest that the two proteins comprising the doublet result from the degradation of the larger molecule during the purification procedure. Both the 119 kDa species and lower molecular weight doublet stimulate fibroblast migration (with half maximal activity in the region of 1-10 pg/ml) and contain a structural domain exhibiting significant amino acid sequence homology with the gelatin-binding fragment (GBF) of fibronectin. Bona fide preparations of GBF, obtained by the limited proteolysis of plasma fibronectin, also stimulate the migration of adult fibroblasts in a similar dose-dependent manner to that of MSF. In spite of this similarity, MSF and GBF differ in terms of a number of biological and biochemical parameters, thereby suggesting that MSF is a distinct gene product and not a proteolytic degradation fragment of fibronectin. MSF stimulates the synthesis of a high molecular weight species of hyaluronic acid (HA). Our current data suggest that the observed effect of MSF on cell migration is actually a secondary consequence of the accumulation of this HA in the collagen matrix. TGF-beta is a potent inhibitor of MSF, both in terms of its effects on cell migration and HA synthesis. As MSF is present in wound fluid, we have suggested that the inhibition of MSF activity by TGF-beta may reflect the antagonistic interaction of these two cytokines in the control of the wound healing process. Our recent data indicate that discrete minority subpopulations of MSF-secreting fibroblasts are also present at specific sites in the healthy adult and that these may undergo a transient and local expansion during wound healing.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Signs and symptoms of "asymptomatic" HIV-1 infection in homosexual men. Multicenter AIDS Cohort Study.

We investigated the long-term health effects of HIV-1 infection in homosexual men not close to developing AIDS by comparing 916 HIV-1-seropositive (SP) men at least 1.67-3.67 years prior to a clinical AIDS diagnosis to 2,161 HIV-1-seronegative (SN) controls. The SP group reported a higher total of 12 distinct symptoms (fatigue, shortness of breath, night sweats, rash, cough, diarrhea, headache, thrush, skin discoloration, fever, weight loss, and sore throat/mouth) than did the SN group (p < 0.0001), corresponding to at least 5.6 more days/year of such symptoms. The SP group had lower body mass index (p < 0.0001) and lower hemoglobin (p < 0.0001). The SP group was more depressed, as measured by CES-D score (p = 0.047), before knowledge of one's serostatus was likely, and became even further depressed (p = 0.038 for increase in depression) after the HIV-1 serostatus test was accessible to high-risk groups. These associations remained unchanged in multivariate models, incorporating other covariates.

Analysis of Variance↗

Roles of peptides in transmission in the enteric nervous system.

Studies of the enteric nervous system have proved to be important in the development of new concepts of the chemical nature of transmission from neurons. In particular, they have revealed the multiplicity of influences that peptides can have on transmission, such as their action as primary transmitters, and the fact that they often act as co-transmitters in enteric neurons. However, in other cases no roles can be attributed to neuropeptides in enteric neurons, and their involvement in short-term changes in excitability seems minor.

Animals↗

The antimicrobial effect of an iron-binding agent on Streptococcus mutans.

The antimicrobial activity of 2,2'-bipyridine, an iron-binding agent, was investigated by incorporating this agent into Scotchbond dental adhesive resin. The growth of Streptococcus mutans on the surface of resin, media and culture vessel was determined by optical density measurements. It was observed that 2,2'-bipyridine exhibited excellent antimicrobial properties.

2,2'-Dipyridyl↗

Neurogenic bladder dysfunction in lumbar intervertebral disc prolapse.

Lumbar disc prolapse with urinary dysfunction is an uncommon condition. The clinical, pathological and follow-up details of 30 patients are presented. Detrusor recovery is rare and most patients are left with an areflexic bladder. Female patients with lumbar disc prolapse and an areflexic detrusor who strain to empty their bladders are likely to develop genuine stress incontinence. This may be managed by the early institution of intermittent self-catheterisation, which may reduce the need for incontinence surgery.

Adult↗

The progression of untreated HIV-1 infection prior to AIDS.

Using a case-control study of untreated men, we investigated the physical, mental, and economic effects of human immunodeficiency virus (HIV-1) infection prior to the diagnosis of acquired immunodeficiency syndrome (AIDS). Beginning 2 to 2.5 years prior to AIDS, case subjects reported more of 12 HIV-1 related symptoms and during the year prior to AIDS, at least 30.6 extra days of these symptoms than did control subjects. Within the 6 months preceding AIDS, case subjects' unemployment rose to 9% (P < or = .05) and depression to 34.2% (P < or = .001). At 6 to 12 months and within 6 months before AIDS, 17.1% and 31.5%, respectively, were anemic, while 37.7% and 64.7% had CD4+ counts less than 200 x 10(6)/L. Diagnosing AIDS at CD4+ counts less than 200 x 10(6)/L could significantly reduce pre-AIDS morbidity. Other implications of these findings are discussed.

Acquired Immunodeficiency Syndrome↗

Risk of developing cytomegalovirus retinitis in persons infected with the human immunodeficiency virus.

This study examines the risk of developing cytomegalovirus (CMV) retinitis as a function of the duration and degree of CD4+ lymphocyte depletion. A retrospective analysis of 135 persons infected with the human immunodeficiency virus (HIV) was performed. Kaplan-Meier estimates for the percentage of patients developing CMV retinitis during the 27-month study period were calculated. Twenty-six patients were diagnosed as having CMV retinitis. In 14 of these patients, T cell phenotyping was done within the 3 months preceding diagnosis. The mean CD4+ lymphocyte count for these patients was 15.6 cells/mm3 (range, 2-33/mm3). At 27 months, the percentage of patients developing CMV retinitis with baseline CD4+ lymphocyte counts of 0-50, 51-100, and 101-250 cells/mm3 was 41.9%, 26.3%, and 14.7%, respectively (log-rank test, p = 0.003). The odds ratio for developing CMV retinitis for those with baseline CD4+ lymphocyte counts of 0-50 cells/mm3 compared with those with CD4+ lymphocyte counts of 101-250 cells/mm3 was 4.62 (p = 0.002). Twenty-four patients had CD4+ lymphocyte counts of < or = 50 cells/mm3 for an average of 13.1 months prior to diagnosis. Twenty-two patients had an acquired immune deficiency syndrome (AIDS)-defining illness diagnosed for an average of 18.0 months prior to the onset of retinitis. CMV retinitis is most likely to develop in patients with AIDS when the CD4+ lymphocyte count is < or = 50 cells/mm3.

Acquired Immunodeficiency Syndrome↗

Evidence that nitric oxide participates in non-adrenergic inhibitory transmission to intestinal muscle in the guinea-pig.

The possible involvement of nitric oxide (NO) in non-adrenergic nerve-mediated relaxations of guinea-pig gastrointestinal smooth muscle was investigated using longitudinal muscle that lies between the taenia of the caecum. Relaxations induced by electrical field stimulation in this preparation are similar to those described in other preparations of guinea-pig intestinal muscle when enteric inhibitory neurons are stimulated; they were blocked by tetrodotoxin (10(-6) M) but were unaffected by guanethidine (10(-6) M). N-Nitro-L-arginine (NOLA) (5 x 10(-5) to 10(-4) M), an inhibitor of NO synthase, and haemoglobin (10(-5) M), which reduces bioavailability of NO, both reduced the amplitude of nerve-mediated relaxations to less than 50%, without affecting the ability of the muscle to relax. These results suggest that NO may play a role in inhibitory neurotransmission to this preparation.

Animals↗

Marsupial possum neurotensin: a unique mammalian regulatory peptide exhibiting structural homology to the avian analogue.

Neurotensin has been isolated from small intestinal extracts of an Australian marsupial, the brush-tailed possum (Trichosurus vulpecula). The primary structure was determined as: pGlu-Leu-His-Val-Asn-Lys-Ala-Arg-Arg-Val-Tyr-Ile-Leu. When compared with bovine neurotensin, marsupial possum neurotensin exhibits four amino acid substitutions. His for Tyr3, Val for Glu4 and Ala for Pro7 are identical with those found in chicken neurotensin. In addition, substitution of Pro10 with Val is unique among all neurotensins sequenced to date. Marsupial possum neurotensin is therefore of unique primary structure, displaying most sequence homology with its avian counterpart. This neurotensin may thus resemble the phylogenetic precursor present at the time of divergence of primitive mammals and birds.

Amino Acid Sequence↗