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Biomedical subjects

R Murray

Publications and source records attributed to R Murray.

At least 217 records · Page 12Linked to original sources
PubMed1992

Lyme neuroborreliosis manifesting as an intracranial mass lesion.

Lyme neuroborreliosis is one of the chronic manifestations of Lyme disease and is caused by the neurotropic spirochete, Borrelia burgdorferi. Two of the three stages of Lyme disease potentially involve the central nervous system: a second stage that may manifest as meningitis, cranial neuritis, or radiculoneuritis; and a third stage, or chronic neuroborreliosis, with parenchymal involvement. The tertiary stage may mimic many conditions, including multiple sclerosis, polyneuropathy, viral encephalitis, brain tumor, vasculitis, encephalopathy, psychiatric illness, and myelopathy. We report a 10-year-old child with signs, symptoms, and radiological manifestations of intracranial mass lesions, without previously recognized manifestations of Lyme disease. This proved to be Lyme neuroborreliosis, documented by histological and serological examination, which responded well to antibiotic therapy. The need to establish a tissue diagnosis of intracranial mass lesions is emphasized, and the utility of a computed tomographic-guided stereotactic system for this purpose is discussed.

Biopsy↗
PubMed1991

A single amino acid substitution in an MHC class I molecule allows heteroclitic recognition by lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes.

Class I molecules of the MHC bind foreign and endogenous peptides allowing recognition by the TCR on CTL. The recognition and killing of cells infected with lymphocytic choriomeningitis virus (LCMV) depends on the recognition of LCMV peptides bound to class I MHC. Mutations in class I MHC molecules have enabled the delineation of regions in the class I molecule important for binding peptides and for interaction with the TCR. We have constructed a library of class I mutants using saturation mutagenesis and report a phenotypic change resulting from a single amino acid substitution that results in the heteroclitic (increased) killing of LCMV-infected cells. This amino acid change, asparagine to serine at position 30, is in a conserved region of the class I molecule contacting the alpha 3 domain. This mutation does not result in increased expression of the class I molecule on the cell surface, does not affect the binding of CD8, and does not affect allogeneic recognition. Cold target experiments show that this heteroclitic killing is due to increased recognition by CTL. These data point toward a critical function for this region of the class I molecule in the binding of peptides or their presentation to CTL.

Animals↗
PubMed1991

MRI in schizophrenia: basal ganglia and white matter T1 times.

The T1 relaxation time of the basal ganglia (putamen, globus pallidus and head of caudate) and of the frontoparietal centrum semiovale was compared between 49 schizophrenic patients and 36 healthy controls. Previous reports of increased T1 time in the basal ganglia were not confirmed, and group differences were not detected within the white matter. Within patients T1 values could not be related to tardive dyskinesia or other clinical features. Normal variation seen in basal ganglia T1 times is described for the first time: lowest values occur in the globus pallidus and highest in the caudate, and values within the putamen increase rostrally.

Adult↗
PubMed1991

Health aspects of carbonless copy paper.

In the past 20 years, there have been numerous reports of skin and mucous membrane disorders allegedly caused by the use of carbonless copy paper, to such an extent that some people in Europe were refusing to work with it and concern was expressed in the European Parliament. In view of its undoubted convenience and superiority over carbon paper, the author was asked by the Commission of the European Communities for a report. Based on visits to manufacturers and users and the investigation of complaints, the conclusion is that, as exposure to the constituents of the paper during its manufacture is considerably greater than in its use and no cases have arisen in his experience in the industry, the complaints are more likely to be attributable to "sick building syndrome" than to the specific effect of any component of the paper.

Dermatitis, Occupational↗
PubMed1991

Physiological responses to glycerol ingestion during exercise.

To study selected cardiovascular, thermoregulatory, and hormonal responses to the consumption of glycerol solutions during exercise, nine subjects cycled for 90 min at 50% peak O2 uptake in a 30 degree C, 45% relative humidity environment. Beverages tested included a 10% glycerol solution (G), a 6% carbohydrate-electrolyte beverage (CE), the 6% carbohydrate-electrolyte beverage plus 4% glycerol (CEG), and a water placebo (WP) ingested at regular intervals during the first 60 min of exercise. The beverages were administered in counterbalanced order with subjects serving as their own controls. Ingestion of the glycerol solutions resulted in an increase in plasma osmolality and attenuation of the decrease in plasma volume associated with the WP treatment (P less than 0.05). Plasma renin activity was highest with WP (P less than 0.05), and G was associated with increased antidiuretic hormone levels (P less than 0.05). Ratings of perceived thirst were lowest for CEG and G, and the frequency of gastrointestinal distress was greatest for G (P less than 0.05). However, no differences among beverage treatments were observed for heart rate, esophageal temperature, sweat rate, ratings of perceived exertion, or changes in cortisol and aldosterone levels. These data indicate that there are no substantial metabolic, hormonal, cardiovascular, or thermoregulatory advantages to the consumption of solutions containing 4 or 10% glycerol during exercise.

Adult↗
PubMed1991

Pre-morbid adjustment and personality in psychosis. Effects of sex and diagnosis.

Pre-morbid schizoid and schizotypal traits and social adjustment were assessed blind to diagnosis by interviewing the mothers of 73 consecutively admitted patients with DSM-III schizophrenia or affective psychosis. Analysis of factors associated with pre-morbid deficits showed a highly significant interaction of diagnosis with sex, such that schizophrenic men showed much greater pre-morbid impairment than either schizophrenic women or men with affective disorder. Poor pre-morbid adjustment predicted an early age at first admission. The results can be explained by a neurodevelopmental disorder in some schizophrenic males.

Adolescent↗
PubMed1991

Schizophrenia and Afro-Caribbeans. A case-control study.

A case-control study was performed using 90% of all first-contact patients with a clinical diagnosis of schizophrenia residing in the London borough of Camberwell between 1965 and 1984. Cases and controls were obtained from the Camberwell psychiatric case register. Controls were those presenting with first episodes of non-psychotic disorders, matched for age, sex and period. The risk of schizophrenia was greater in those of Afro-Caribbean ethnicity, irrespective of age, gender or place of birth. This risk increased over the study period. The results cannot be explained by changes in the age, gender or ethnic structure of the local population. Effects of misdiagnosis or change in diagnostic practice were reduced by using uniform operational criteria. Possible explanations include maternal exposure to unfamiliar infective agents, a differential fall in the age at onset of illness, or worsening social adversity.

Black or African American↗
PubMed1991

Responses to varying rates of carbohydrate ingestion during exercise.

The purpose of this study was to determine how the ingestion of carbohydrate at varying rates influences physiological, sensory, and performance responses to prolonged exercise at 65-75% VO2max. Ten subjects ingested either a water placebo (WP) or carbohydrate solutions formulated to provide glucose at the rates of 26, 52, and 78 g, h-1 during 2 h of cycling exercise in a cool (10 degrees C) environment. Beverages were administered in a double-blind, counterbalanced design. A 4.8 km performance test followed each 2 h session. The average time required to complete the performance test was less with the carbohydrate feedings than with WP: mean (+/- SE) for WP = 505.0 +/- 18.7 s. 26 g.h(-1) = 476.0* +/- 8.8 s. 52 g.h(-1) = 483.8 +/- 12.7 s. 78 g.h(-1) = 474.3* +/- 19.1 s; *P less than 0.05 vs WP. Carbohydrate feeding resulted in higher plasma glucose and insulin, and lower free fatty acid concentrations than did WP. Changes in plasma osmolality, plasma volume, rectal temperature, lactate, heart rate, respiratory exchange ratio, ratings of perceived exertion, and sensory responses were similar among beverage treatments. Compared with WP, ingestion of the glucose beverages minimized changes in plasma ACTH and cortisol. In summary, carbohydrate feeding at the rates of 26 and 78 g.h(-1) was associated with improved exercise performance. The data further indicate that a dose-response relationship does not exist between the amount of carbohydrate consumed during exercise and exercise performance.

Adult↗
PubMed1990

Prostaglandin endoperoxide/thromboxane A2 receptor desensitization. Cross-talk with adenylate cyclase in human platelets.

Platelet activation by the prostaglandin endoperoxide (PGH2)/thromboxane (Tx) A2 analog, U46619, involves stimulation of phospholipase (PL) C and an increase in intracellular calcium via distinct receptor subtypes. Agents which stimulate adenylate cyclase inhibit platelet function. We demonstrate that PGH2/TxA2 receptor desensitization is associated with enhanced stimulation of platelet cyclic AMP by the prostacyclin analog, iloprost and by forskolin. Sensitization of adenylate cyclase is mediated via the PGH2/TxA2 receptor subtype which activates PLC, as it is blocked by the specific antagonist, GR32191 (Takahara, K., Murray, R., FitzGerald, G. A., and Fitzgerald, D. J. (1990) J. Biol. Chem. 265, 6838-6844). This effect is not observed in platelets desensitized with thrombin or platelet activating factor and is not mediated by protein kinase C. Prior exposure of platelets to platelet activating factor results in much greater desensitization of PGH2/TxA2-induced aggregation (mean 64%) compared with calcium stimulation (mean 18%), consistent with selective heterologous desensitization of the PLC-linked PGH2/TxA2 receptor subtype. Platelet activation by PGH2/TxA2 is a tightly regulated process, involving both homologous desensitization of at least two receptor subtypes and sensitization of the platelet adenylase cyclase system.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

The response to thromboxane A2 analogues in human platelets. Discrimination of two binding sites linked to distinct effector systems.

Thromboxane A2 (TXA2) induces platelet shape change, secretion, and aggregation. Using a novel TXA2/prostaglandin endoperoxide receptor antagonist, [1r-[1 alpha(Z),2 beta,3 beta,5 alpha]]-(+)-7-[5-[[(1,1'- biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1-piperidinyl) cyclopentyl]-4-heptenoic acid hydrochloride (GR32191), we demonstrate that these responses are mediated by at least two receptor-effector systems. GR32191 non-competitively inhibited platelet aggregation to the TXA2 mimetics, (15S)-hydroxy-11,9-(epoxymethano) prostadienoic acid (U46619) and [1S-(1 alpha,2 beta(5Z),3 alpha (1E,-3S), 4 alpha)]-7-[3-(3-hydroxy-4-(p-iodophenoxy)-1-butenyl)7- oxabicyclo[2.2.1]hept-2yl]-5-heptenoic acid by binding irreversibly to a TXA2/prostaglandin endoperoxide receptor. Dissociation of [3H]GR32191 from human platelets demonstrated two specific binding sites, one which was rapidly dissociating and a site to which binding was essentially irreversible. Stimulation by U46619 of platelets incubated with GR32191 and subsequently washed to expose the reversible binding site failed to aggregate or to secrete [3H]5-hydroxy-tryptamine; formation of inositol phosphates and activation of protein kinase C were markedly suppressed. In contrast, platelet shape change and calcium stimulation remained at 90% of control. Furthermore, stimulation of the reversible binding site with U46619 induced aggregation in the presence of ADP, demonstrating its functional importance in amplifying the response to other agonists. These data suggest that TXA2 mediates platelet activation through at least two receptor-effector systems; one linked to phospholipase C activation, resulting in platelet aggregation and secretion and a second site mediating an increase in cytosolic calcium and platelet shape change.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

Growth-promoting activity of IL-1 alpha, IL-6, and tumor necrosis factor-alpha in combination with IL-2, IL-4, or IL-7 on murine thymocytes. Differential effects on CD4/CD8 subsets and on CD3+/CD3- double-negative thymocytes.

Many cytokines (including IL-1, IL-2, IL-4, IL-6, and TNF-alpha) have been shown to induce thymocyte proliferation in the presence of PHA. In this report, we demonstrate that certain cytokine combinations induce thymocyte proliferation in the absence of artificial comitogens. IL-1 alpha, IL-6, and TNF-alpha enhanced the proliferation of whole unseparated thymocytes in the presence of IL-2, whereas none of them induced thymocyte proliferation alone. In contrast, of these three enhancing cytokines, only IL-6 enhanced IL-4-induced proliferation. We also separated thymocytes into four groups based on their expression of CD4 and CD8, and investigated their responses to various cytokines. The results indicate that each cytokine combination affects different thymocyte subsets; thus, IL-1 alpha enhanced the proliferation of CD4-CD8- double negative (DN) thymocytes more efficiently than IL-6 in the presence of IL-2, whereas IL-6 enhanced the responses of CD4+CD8- and CD4-CD8+ single positive (SP) thymocytes to IL-2 or IL-4 better than IL-1 alpha. TNF-alpha enhanced the proliferation of both DN and both SP subsets in the presence of IL-2 and/or IL-7. None of these combinations induced the proliferation of CD4+CD8+ double positive thymocytes. Finally, DN were separated into CD3+ and CD3- populations and their responsiveness was investigated, because recent reports strongly suggest that CD3+ DN thymocytes are a mature subset of different lineage rather than precursors of SP thymocytes. CD3+ DN proliferated in response to IL-7, TNF-alpha + IL-2, and IL-1 + IL-2. CD3- DN did not respond to IL-7 or to IL-1 + IL-2, but did respond to TNF-alpha + IL-2. Finally, we detected TNF-alpha production by a cloned line of thymic macrophages, as well as by DN adult thymocytes. These results suggest that cytokines alone are capable of potent growth stimuli for thymocytes, and indicate that different combinations of these molecules act selectively on thymocytes at different developmental stages.

Animals↗
PubMed1990

Thromboxane A2 synthesis in pregnancy-induced hypertension.

Urinary excretion of thromboxane B2 metabolites as markers of thromboxane A2 synthesis was measured in eight patients with moderate to severe pregnancy-induced hypertension and in six normotensive pregnant women at term. Excretion of both 2,3-dinor-TxB2 (median 3919, range 683-16,680 pg/mg creatinine) and 11-dehydro-TxB2 (median 10,187, range 434-57,203 pg/mg creatinine) was significantly higher in the patients with pregnancy-induced hypertension than in the normotensive pregnant group (927[273-1343] and 774[500-2760] pg/mg creatinine, respectively). Thromboxane metabolite excretion correlated with mean arterial blood pressure, plasma lactate dehydrogenase, and platelet count which are indices of the severity of pregnancy-induced hypertension. Excretion of both metabolites fell rapidly post partum in parallel with resolution of clinical signs. Thus, increased thromboxane A2 biosynthesis correlates with disease severity and may have a pathogenetic role in pregnancy-induced hypertension. These findings provide a rationale for the use of aspirin in the treatment as well as in the prevention of this disorder.

Adolescent↗
PubMed1990

Tumor necrosis factor-alpha and P40 induce day 15 murine fetal thymocyte proliferation in combination with IL-2.

Cytokines are known to play a key role in the development of several hemopoietic lineages including lymphocytes. Two cytokines: IL-4 (in the presence of PMA) and IL-7 have been shown to induce immature fetal thymocyte proliferation. It has also been suggested that IL-2 plays an important role in fetal T cell development. In this report, we investigated the effects of several cytokines (known to be growth factors for T-lineage cells) on fetal thymocyte proliferation. Our results indicate that: 1) TNF-alpha and a newly described cytokine, P40, enhance fetal thymocyte proliferation stimulated by IL-2 (but not IL-4 or IL-7). 2) The enhancement induced by P40 is not mediated by TNF-alpha because blocking antibodies against this cytokine failed to inhibit this response. 3) IL-4 inhibits fetal thymocyte proliferation in response to TNF-alpha + IL-2 or to IL-7 but not to P40 + IL-2. Finally, 4) the proliferating cells to all cytokine combinations used were Thy-1+. These observations suggest that these cytokine combinations induce independent pathways of T cell proliferation in the developing thymus.

Animals↗
PubMed1990

Frequency of 47, +21 in cells of blood cultures from couples with habitual spontaneous abortion.

Karyotyped specimens of peripheral blood from 1,055 chromosomally normal individuals (573 females, 482 males) presenting with habitual spontaneous abortion were examined for aneuploidy. Trisomy 21 was noted in six of 14,802 cells. These data were not significantly different from those obtained on chromosomes 19 and 20, or the data obtained from three different, smaller, control groups. The low rate of trisomy 21 cells found in this study suggests that we cannot extrapolate from events in somatic cells in mitosis to nondisjunction events in meiosis.

Abortion, Habitual↗