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R Murray

Publications and source records attributed to R Murray.

At least 127 records · Page 7Linked to original sources
PubMed1997

The molecular genetics of schizophrenia: progress so far.

In 1988, a report of a genetic linkage between schizophrenia and markers on chromosome 5 caused considerable excitement. Many hoped that a cause for schizophrenia had been found. Unfortunately, subsequent results failed to replicate the finding, and there was little progress in the molecular understanding of the disorder over the next five years. However, within the past two years, there have been reports of positive linkages on chromosome arms 22q and 6p that, unlike previous reports, have received support from several teams. Here, we review the evidence for these linkages, as well as findings from association studies that have not yet received as much independent confirmation.

Adolescent↗
PubMed1997

One-year status of homeless mentally ill clients who completed a transitional residential program.

Of 228 homeless, severely persistently mentally ill clients admitted within a 5 1/2 year period to a transitional residential program, 179 (79%) remained in contact with staff for at least one year post-discharge. Housing was maintained by 141 (78%) of the clients for at least one year. Entitlements increased from admission, to discharge, to one year post-discharge. Clients maintaining contact for at least one year post-discharge were likely to have participated in two or more day treatment programs during residence. Success of the Program may be partly attributed to the staff's vigilance in maintaining post-discharge client contact.

Adult↗
PubMed1997

Persistence of pulmonary pathology and abnormal lung function in IL-3/GM-CSF/IL-5 beta c receptor-deficient mice despite correction of alveolar proteinosis after BMT.

Mice deficient for the IL-3/GM-CSF/IL-5 beta c receptor (beta cR KO) develop lung disease similar to that seen in human pulmonary alveolar proteinosis (PAP) which includes lymphocytic infiltration around airways and vessels and the progressive accumulation of surfactant and macrophages within the alveolar space. We investigated bone marrow transplantation (BMT) as a curative treatment of PAP in beta cR KO mice by semiquantitative histologic analysis and evaluation of pulmonary function. BMT from wild-type (WT) donors into lethally irradiated beta cR KO recipients (WT --> KO) led to the complete resolution of alveolar protein accumulation and to normalization of BAL fluid cellularity and macrophage morphology. However, detailed microscopic analysis of lung tissue revealed the persistence of significant cellular infiltrates in WT --> KO recipients which were equivalent to those seen in KO --> KO animals. Evaluation of pulmonary function demonstrated that only dynamic compliance (Cdyn) and not airway conductance (G[L]) was significantly improved in the WT --> KO group compared to KO --> KO animals and that both of these measurements remained significantly abnormal when compared to WT --> WT controls. We conclude, that although BMT for PAP reverses alveolar macrophage and protein accumulation, it does not decrease the interstitial inflammatory component of this disease. The importance of this residual pathology is demonstrated by the incomplete correction of alveolar function (Cdyn) and lack of improvement in increased airway resistance (G[L]). These findings may have important implications with regard to the extent that BMT can be considered a potential curative procedure for this clinical disorder.

Animals↗
PubMed1997

Catechol-O-methyltransferase Val158Met polymorphism: frequency analysis in Han Chinese subjects and allelic association of the low activity allele with bipolar affective disorder.

Catechol-O-methyltransferase catalyses the O-methylation of biologically active or toxic catechols and is a major component of the metabolism of drugs and neurotransmitters such as L-dopa, noradrenaline, adrenaline, and dopamine. Human catechol-O-methyltransferase activity is an autosomal partially dominant trait and is strongly associated with a valine to methionine substitution at codon 158 of the protein. About 25% of Caucasians have low activity, 50% intermediate activity and 25% high activity as determined by either phenotypic or genotypic measurement. In black populations, the low activity allele (Met158; COMTL) is less frequent with about 7% being homozygous. Using a PCR based genotyping assay, we report that the Met158 allele is also less frequent in normal Han Chinese subjects with about 3% of the population being homozygous. Because of its role in catecholamine metabolism and several lines of evidence pointing to a locus for psychosis near the COMT gene on chromosome 22q11, we have analysed the COMT Val158Met polymorphism as a candidate susceptibility factor for bipolar affective disorder. We report an association between bipolar affective disorder and the Met158 allele (p = 0.004) and genotype (p = 0.01) in 93 affected Chinese subjects and 98 controls. We hypothesize that either the low activity allele of catechol-O-methyltransferase is a risk factor for bipolar affective disorder in Chinese populations or is in linkage disequilibrium with a nearby susceptibility gene or polymorphism.

Bipolar Disorder↗
PubMed1997

Tardive dyskinesia: who is at risk?

Tardive dyskinesia (TD) has been associated with female gender, affective symptoms and good outcome, but also with negative symptoms, cognitive deterioration and deteriorating illness course. Furthermore, antipsychotic medication is thought to be an important risk factor, yet abnormal movements also occur in patients who have never received such medication. We followed 166 subjects with recent onset of psychotic illness and brief previous exposure to antipsychotic medication. Information on 17 previously reported risk factors was available for 125 patients at baseline and, for factors that vary over time, again at follow-up 4 years later (median, 50 months; interquartile range, 29-70). Movement disorder was assessed at follow-up using the Abnormal Involuntary Movement Scale (AIMS). Six noninteracting variables were independently associated with the 4-year risk of TD: male sex (OR, 2.5; 95% CI, 1.1-5.0), age (OR over quartiles at baseline, 1.6; 95% CI, 1.1-2.2), lack of insight at baseline (OR over four categories, 2.0; 95% CI, 1.2-3.2), time on antipsychotics during the follow-up period (OR over quartiles, 2.3; 95% CI, 1.5-3.4), an increase in negative symptoms during the follow-up period (OR over quartiles, 1.7; 95% CI, 1.2-2.5), and alcohol/drug misuse at follow-up (OR, 3.0; 95% CI, 1.3-7.4). The presence of individual risk factors was found to be of little use as a screening test for subsequent clinically relevant TD. Given the absence of a risk factor, however, the probability that an individual would not develop TD was high. These results suggest that two discrete effects may operate to increase the risk of TD, namely an exogenous factor (medication, drugs), and an illness-related factor, the highest risk being conferred by deteriorating illness course in male patients.

Adult↗
PubMed1997

The cytokine stew and innate resistance to L. monocytogenes.

The Listeria monocytogenes (L. monocytogenes) infection model has been a useful system to evaluate the cellular interactions leading to host immunity. The initiation of the innate immune response in naive animals and subsequent progression to acquired immunity represent an integrated system with numerous layers of complexity. Coincident with experimental infection is the induction of cytokines. Cytokines, which are soluble mediators of cell growth, maintenance and function, from a network of pleiotropic stimuli that serve as one of the main driving forces for the progressive development of cellular responses. A variety of in vivo approaches, such as injection of the recombinant cytokines themselves or antibodies to neutralize their activity, have been used to define these stimuli. Perhaps one of the most useful tools is that of germline-manipulated animals. One of the many cytokines implicated in resistance to L. monocytogenes infection is interleukin (IL)-6, a molecule associated with diverse infectious and pathophysiological disease states. This review concentrates on various cytokines (IL-1, TNF alpha, IFN-gamma, IL-12, IL-10 and the colony-stimulating factors (CSF)) thought to play a role during the innate host response to L. monocytogenes infection, with a special emphasis on studies using IL-6-deficient mice. Additionally, we show unpublished data obtained when the concepts learned from L. monocytogenes infection in IL-6-deficient mice were applied to other infection models.

Animals↗
PubMed1997

Gastric emptying and plasma deuterium accumulation following ingestion of water and two carbohydrate-electrolyte beverages.

The purpose of this study was to compare the gastric emptying rates (GER) of water, a 6% carbohydrate (CHO) beverage, and a 20% CHO beverage and to contrast those rates against the rate at which deuterium oxide in the drinks accumulated in plasma (DAR) following beverage ingestion. Ten subjects (8 males, 2 females) cycled at 60% VO2max for 70 min; at 13 min, the subjects ingested 400 ml of one of the beverages. The GER and DAR of water and 6% CHO were similar, while GER and DAR were both significantly slowed by ingestion of 20% CHO. Although there was a significant correlation (r = .63, p < .05) between GER and DAR, only 40% of the variation in DAR could be accounted for by variation in GER. These data support the contention that DAR is partially determined by GER, with differences in the rate of fluid absorption across the intestine and other factors accounting for the remaining variation in DAR.

Adult↗
PubMed1997

The effects of beverage carbonation on sensory responses and voluntary fluid intake following exercise.

The effects of carbonated beverages on sensory acceptability and voluntary fluid intake after exercise were examined. The level of carbonation in a 6% carbohydrate (CHO) electrolyte drink was systematically varied (0, 1.1, 2.3, and 3.0 volumes of CO2), and its impact was assessed in 52 adults following 30 min of exercise. The perception of carbonation intensity closely tracked the differences in physical carbonation levels presented, with all perceived intensities significantly different from each other (p < .01). Overall sensory acceptability, perceived thirst quenching, and perceived sweetness were significantly lower for 2.3-vol CO2 and 3.0-vol CO2 than for 0-vol CO2 and 1.1-vol CO2 (p < .01). Perceived throatburn was significantly higher for 2.3-vol CO2 and 3.0-vol CO2 than for 0-vol CO2 and 1.1-vol CO2 (p < .01). Total fluid intake for 0-vol CO2 and 1.1-vol CO2 was significantly higher than for 2.3-vol CO2 (p < .05), which was significantly higher than for 3.0-vol CO2 (p < .05). It was concluded that levels of carbonation equal to or in excess of 2.3-vol CO2 negatively impact drink acceptability and voluntary fluid intake.

Adult↗
PubMed1997

Impaired resistance to the development of toxoplasmic encephalitis in interleukin-6-deficient mice.

The role of interleukin-6 (IL-6) in the pathogenesis of toxoplasmic encephalitis (TE) was examined by using IL-6-targeted mutant (IL-6(-/-)) mice. At 4 and 8 weeks after infection with the ME49 strain of Toxoplasma gondii, significantly greater numbers of T. gondii cysts and areas of inflammation associated with tachyzoites were observed in brains of IL-6(-/-) mice than in those of control mice. Large areas of necrosis were observed only in brains of IL-6(-/-) mice. Tachyzoites were frequently detected in the areas of necrosis, suggesting that necrosis was caused by proliferation of the parasite. These results indicate that IL-6 is protective against development of TE by preventing formation of T. gondii cysts and proliferation of tachyzoites in brains of infected mice. Whereas in brains of control mice, large numbers of inflammatory cells were always observed in areas where tachyzoites were detected, in brains of IL-6(-/-) mice, only small numbers of inflammatory cells were observed in many areas with tachyzoites. Lymphocyte preparations isolated from brains of infected control mice had significantly higher ratios of gamma/delta T cells and CD4+ alpha/beta T cells but lower ratios of CD8+ alpha/beta T cells compared to those of infected IL-6(-/-) mice. There were no differences in the ratios of these T-cell subsets in spleens between these mice. The amounts of mRNA for gamma interferon (IFN-gamma) detected by reverse transcriptase PCR were significantly smaller in brains of IL-6(-/-) mice than in those of control mice, whereas amounts of IL-10 mRNA were greater in the former than in the latter. IL-6 mRNA was detected only in infected control mice. The protective activity of IL-6 against development of TE appears to be through its ability to stimulate IFN-gamma production and induce infiltration and accumulation of different T-cell subsets in brains of infected mice.

Animals↗
PubMed1997

Psychopathological syndromes and familial morbid risk of psychosis.

BACKGROUND: Familial liability in the functional psychoses had traditionally been examined by comparing mutually exclusive diagnostic categories. This study examines overlapping psychopathological dimensions in relation to familial morbid risk of psychosis. METHOD: We tested for associations between seven factor-analysis derived psychopathological dimensions and familial morbid risk of psychosis, in a sample of 150 patients with recent-onset functional psychosis and 548 of their first-degree relatives. RESULTS: A syndrome characterised by affective blunting and insidious and early onset of illness, non-specifically predicted psychosis in the first-degree relatives, whereas a manic syndrome specifically predicted affective psychosis in the relatives. No other main effects were observed, but there were interactions with proband diagnosis: a syndrome characterised by bizarre behaviour, inappropriate affect, catatonia and poor rapport predicted psychosis in relatives of schizophrenic probands, and a syndrome of depressive: symptoms predicted psychosis in relatives of schizoaffective probands. Positive symptoms were not associated with illness in the relatives. CONCLUSIONS: Genetic effects in the functional psychoses may comprise non-specific components that canalise a general, early-onset, affective blunting phenotype and several other, more specific, influences on phenotypic variation.

Adult↗
PubMed1997

A controlled family study of late-onset non-affective psychosis (late paraphrenia).

BACKGROUND: The relationship between those schizophrenia-like conditions that have their onset in late life and early-onset schizophrenia is unclear. Very few family history studies of patients with late-onset psychosis have been reported, and it is not known whether their relatives have an increased risk of psychosis. METHOD: Information was collected on the psychiatric morbidity of 269 first-degree relatives of patients with schizophrenia or delusional disorder with an onset after the age of 60 (late paraphrenia), and 272 first-degree relatives of healthy elderly control subjects, using a research diagnostic instrument. RESULTS: With a narrow age range (15-50 years) at risk, the estimated lifetime risk of schizophrenia was 1.3% in the relatives of both cases and controls. With a wider age range (15-90 years) at risk, estimated lifetime risk of schizophrenia was 2.3% for the relatives of cases and 2.2% for the relatives of controls. However, depression was significantly more common among the relatives of cases than controls. CONCLUSIONS: Those schizophrenia-like psychoses with onset in late life are not genetically associated with schizophrenia.

Adult↗
PubMed1996

Hematopoiesis in mice lacking the entire granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 functions.

Interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5 are major hematopoietic cytokines produced by activated T cells and exhibit similar biologic activities by signaling through a common receptor subunit (beta c). Mice lacking beta c show a pulmonary alveolar proteinosis-like disease and reduced numbers of peripheral eosinophils, which are explained by the lack of GM-CSF and IL-5 function, respectively. However, beta c-deficient hematopoietic cells do respond to IL-3 normally, probably through an additional beta subunit of the IL-3 receptor (beta IL3) that is present in the mouse. Thus, almost normal hematopoiesis in beta c-deficient mice may be caused by functional redundancy between IL-3 and GM-CSF. To clarify the role of the entire IL-3/GM-CSF/IL-5 system in hematopoiesis in vivo, we crossed the beta c mutant mice with mice deficient for IL-3 ligand to generate mice lacking the entire IL-3/GM-CSF/IL-5 functions. The double-mutant mice were apparently normal and fertile. The severity of the lung pathology in the beta c/IL-3 double-mutant mice showed normal hemodynamic parameters except for reduced numbers of eosinophils and the lack of eosinophilic response to parasites, which were also found in beta c mutant mice. The immune response of the beta c/IL-3 double-mutant mice to Listeria mono-cytogenes was normal, as was hematopoietic recovery after administration of the cytotoxic drug, 5-fluorouracil. Although it has been believed that IL-3/GM-CSF/IL-5 produced by activated T cells play a major role in expansion of hematopoietic cells in emergency, our results indicate that the entire function of IL-3/GM-CSF/IL-5 is dispensable for hematopoiesis in emergency as well as in the steady state. Thus, there must be an alternative mechanism to produce blood cells in both situations.

Animals↗
PubMed1996

Explaining sex differences in course and outcome in the functional psychoses.

We addressed the following three questions: (i) are there sex differences in outcome in the functional psychoses?, (ii) what is their effect size, and which variables mediate the effect of sex on outcome?, (iii) is the effect of sex diagnosis-specific? In a prospective study of 166 patients with recent onset psychosis, we established that 4-year outcome was more favourable for women. Female patients more often had a remitting illness course (OR = 3.0; 95% CI: 1.5-5.9), were living independently 14% (4-24%) more of the time, had less evidence of negative symptoms over the follow-up period (OR = 0.3; 0.2-0.7) and were more likely to be employed at follow-up (3.6; 1.8-7.6). The findings did not appear diagnosis-specific, although the sample size was small to test for interaction with diagnostic category. Baseline occupational and social adjustment, clinical expression of illness and age and type of onset explained up to 60% of the sex effect. The processes underlying these factors mediate the effect of sex on outcome.

Adolescent↗
PubMed1996

Inhibition of gamma delta T cell development and early thymocyte maturation in IL-7 -/- mice.

While early thymic T cell precursor populations and their maturational sequence have been recently identified, the signals driving differentiation are unknown. While cytokines may play an integral role in T cell development, various mouse models rendered genetically deficient for specific cytokines do not display abnormalities in T cell development. Recently, we have generated IL-7 -/- mice and reported that IL-7 plays a unique and nonredundant role in lymphopoiesis. These mice displayed a 10- to 20-fold reduction in the total number of T and B cells. Here, we show that IL-7 -/- mice display a sharp reduction in both the frequency and absolute number of adult thymic gamma delta T cells while retaining normal frequencies of alpha beta T cells. This defect in gamma delta T cell production extends to peripheral organs as IL-7 -/- mice are essentially devoid of splenic and intestinal intraepithelial gamma delta T cells. This aberrant phenotype was traced back to impaired fetal gamma delta T cell maturation. In the absence of IL-7, differentiation of immature V gamma 3 low-CD24+ fetal T cells to mature V gamma 3 high CD24- cells is inhibited. In contrast, NK cell maturation appears to be only mildly affected in the absence of IL-7. To further clarify the role of IL-7 in thymic development, detailed analysis of CD3-4-8- thymic precursors was performed. A partial inhibition in the differentiation of CD44+25+ pro-T cells into CD44-25+ pre-T cells was observed. Unexpectedly, the lack of IL-7 resulted in decreased expression of CD117 (c-kit) on both CD4 low and pro-T cells, suggesting that IL-7 may influence the expression of other cytokine receptors involved in early hemopoietic development. Together, these data clarify the developmental abnormalities during T cell development due to the absence of IL-7.

Animals↗
PubMed1996

Transmission of serum hepatitis. 1970.

There is evidence that transmission of serum hepatitis is associated with transmission of virus-like particles, approximately, 20 millimicron in diameter, containing the Australia or serum hepatitis (SH) antigen, which is currently referred to as the hepatitis associated antigen (HAA). Virus-like particles containing HAA were in the following materials, inoculation of which produced serum hepatitis: (1) a pool of human plasma, (2) serum obtained during the acute phase of hepatitis from a recipient of the plasma pool, (3) a preparation of human thrombin, and (4) serum from a proved hepatitis carrier. The HAA appeared in the serum samples of 61 individuals inoculated with these materials; serum hepatitis developed in 38 of them. Inoculation of dilutions of the plasma pool showed that serum hepatitis can be transmitted by materials containing HAA in amounts too low to be detected by current techniques.

Carrier State↗