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R Murray

Publications and source records attributed to R Murray.

At least 163 records · Page 9Linked to original sources
PubMed1995

Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder.

We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significant only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant.

Alleles↗
PubMed1995

Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine.

Interleukin (IL)-7 is a potent stimulus for immature T and B cells and, to a lesser extent, mature T cells. We have inactivated the IL-7 gene in the mouse germline by using gene-targeting techniques to further understand the biology of IL-7. Mutant mice were highly lymphopenic in the peripheral blood and lymphoid organs. Bone marrow B lymphopoiesis was blocked at the transition from pro-B to pre-B cells. Thymic cellularity was reduced 20-fold, but retained normal distribution of CD4 and CD8. Splenic T cellularity was reduced 10-fold. Splenic B cells, also reduced in number, showed an abnormal population of immature B cells in adult animals. The remaining splenic populations of lymphocytes showed normal responsiveness to mitogenic stimuli. These data show that proper T and B cell development is dependent on IL-7. The IL-7-deficient mice are the first example of single cytokine-deficient mice that exhibit severe lymphoid abnormalities.

Animals↗
PubMed1995

Computerized brain tissue classification of magnetic resonance images: a new approach to the problem of partial volume artifact.

Due to the finite spatial resolution of digital magnetic resonance images of the brain, and the complexity of anatomical interfaces between brain regions of different tissue type, it is inevitable that some voxels will represent a mixture of two or three different tissue types. Outright assignment of such "bipartial" or "tripartial" voxels to one class or another is more problematic and less reliable than assignment of "full-volume" voxels, wholly representative of a single tissue type. We have developed a computerized system for brain tissue classification of dual echo MR data, which uses a polychotomous logistic model for discriminant analysis, combined with a Bayes allocation rule incorporating differential prior probabilities, and spatial connectivity tests, to assign each voxel in the image to one of four possible classes: gray matter, white matter, cerebrospinal fluid, or unclassified. The system supports automated volumetric analysis of segmented images, has low operational overheads, and compares favorably with previous multivariate or "multispectral" approaches to brain MR image segmentation in terms of both validity (bootstrap misclassification rate = 3.3%) and interoperator reliability (intra-class correlation coefficients for all three tissue classes > 0.9). We argue that these improvements in performance stem from better methodological management of the related problems of non-Normality of MR signal intensity values and partial volume artifact.

Artifacts↗
PubMed1995

Aromatase inhibition with 4-OHAndrostenedione after prior aromatase inhibition with aminoglutethimide in women with advanced breast cancer.

One hundred and twelve post menopausal or post oophorectomy women with advanced breast cancer (BC) who had all previously had aminoglutethimide (AG) were treated with the potent aromatase inhibitor 4-hydroxy androstenedione (4-OHA). Twenty three women (21%) had a partial response to 4-OHA while another twenty five patients (22%) had stabilization of previously progressing disease. Patients responded to 4-OHA both after previously responding to then relapsing on, and after failing to respond to aminoglutethimide. Toxicity was minimal. This study shows that potent aromatase inhibition with 4-OHA is effective in women with advanced BC who have already been treated with a less potent aromatase inhibitor, and suggests that relative changes in oestrogen levels may be more important than absolute levels.

Adult↗
PubMed1995

Increasing age is a risk factor for psychosis in the elderly.

We examined the association between ageing and the administrative incidence rate of late onset (after age 59) non-organic, non-affective psychosis in two samples of patients aged 60 years or older who were first admitted to hospital in (1) The Netherlands between 1978 and 1992 (n = 8010) and (2) nine regional health authorities in England and Wales (n = 1777) between 1976 and 1978. There was a linear trend in the association between increasing age and first admission rates for non-organic, non-affective psychosis in the elderly, after adjustment for the possible confounding effects of time trend and gender, corresponding to an 11% increase in the incidence with each 5-year increase in age. These observations support a connection between degenerative brain processes and onset of non-affective psychosis in the elderly.

Aged↗
PubMed1995

Innovative programming in a community service center.

A Community Center in a downtown urban area offers comprehensive services that provide continuity and choice to homeless and poor people. Emphasis is on outreach, through a Day Treatment Program for severely, persistently mentally ill homeless, a mobile outreach team, and neighborhood services, and/or employment, including a restaurant and Employment Reintegration Program. The Center is an example of how professionals, community and business leaders, and citizens can unite to assist clients and how programs can evolve from clients' requests and participation in services. The Center's programming can be followed in any community in this health care reform era.

Community Mental Health Centers↗
PubMed1995

No association between the c2 allele at the cytochrome P450IIE1 gene and alcohol induced liver disease, alcohol Korsakoff's syndrome or alcohol dependence syndrome.

Cytochrome P450IIE1 metabolises, and is induced by ethanol. The 5' regulatory sequence of the gene is polymorphic; that identified by the c2 allele has been shown by transfection studies to confer an increased rate of transcription. A recent report indicating an association between this allele and alcohol induced cirrhosis suggests that it may contribute to the genetic vulnerability to this disease. We have examined this polymorphism in patients of western European origin with alcohol induced cirrhosis, alcohol Korsakoff's syndrome and alcohol dependence syndrome. We were unable to detect any association between this allele and any of these diseases.

Alcohol Amnestic Disorder↗
PubMed1995

Components of an effective transitional residential program for homeless mentally ill clients.

UNLABELLED: Review of clinical records of 228 former clients of a Transitional Residential PROGRAM for severely, persistently mental ill homeless persons was conducted to examine PROGRAM results for completers and noncompleters. Of the 228 clients, 110 (48.3%) completed the PROGRAM: they became psychiatrically stabilized, found secure housing, and began receiving disability pensions. Completers participated in significantly more activities than noncompleters. Psychiatric diagnosis was unrelated to successful PROGRAM completion. Individuals who left against advice had significantly fewer previous hospitalizations.

Activities of Daily Living↗
PubMed1995

Cerebral hemispheric asymmetry revisited: effects of handedness, gender and schizophrenia measured by radius of gyration in magnetic resonance images.

Abnormal patterns of cerebral hemispheric asymmetry have been inconsistently reported in association with schizophrenia. Radius of gyration (Rg) is a measure of the mean dispersion of points in a radially organized structure about that structure's centre of gravity. We developed computerized methods for estimating Rg of the magnetic resonance image (MRI) boundary between cortex and subcortex, and applied these methods to measurement of cerebral hemispheric asymmetry in 37 schizophrenics (SZs) and 30 controls (CONs). In right-handed CONs, Rg of right brain boundaries was significantly greater than Rg of left brain boundaries; in left-handed CONs, Rg of left brain boundaries was significantly greater than Rg of right brain boundaries. In right-handed males (both SZ and CON) there were significant differences in Rg between hemispheres; whereas in females (both SZ and CON), there were no such differences. Right-handed male SZs (N = 26) were distinguished by reversal of the right-handed male CON pattern of interhemispheric difference in Rg, and by global reduction in Rg of right brain boundaries. These was no evidence for significant abnormality of Rg in right-handed female SZs (N = 7). There findings suggest an important interactive effect of gender and schizophrenia on lateralized cerebral structure.

Adult↗
PubMed1995

The relationship between patterns of alcohol consumption and body weight. Lung Health Study Research Group.

BACKGROUND: Reported alcohol intake has an inverse association with body weight in women but is related to greater weight or no differences in weight in men. However, the relationship of alcohol consumption to weight appears to be less reliable in cigarette smokers and may be modified by the pattern of alcohol intake. The objective of this investigation was to examine the relationship of both aggregate alcohol intake and daily modal intake to body mass index (BMI) in male and female cigarette smokers. METHODS: Cigarette smoking habits, body weight, and alcohol intake were assessed during screening for a clinical trial of early intervention for chronic obstructive pulmonary disease. Analyses are based on 3616 men and 2141 women cigarette smokers between 35 and 60 years of age. RESULTS: There were no significant differences in BMI between alcohol drinkers and abstainers in either men or women. However, following regression adjustment for age, education, and cigarettes/day, total weekly alcohol intake was related to a lower BMI in both men and women, whereas a greater modal intake (drinks on a day alcohol is consumed) was related to a greater BMI in both men and women. CONCLUSIONS: The association of alcohol use to BMI in moderate to heavy cigarette smokers appears to be modified by the pattern of intake. Although the factors underlying this association are unclear, increased modal alcohol intake may serve as a marker for dietary or behavioural factors linked to greater body weight in cigarette smokers.

Adult↗
PubMed1995

Suggestive evidence for linkage of schizophrenia to markers on chromosome 13q14.1-q32.

Family, twin and adoption studies highlight the influence of genes in the aetiology of schizophrenia, though the mode of inheritance is unclear. We have been conducting a systematic search for major genes in schizophrenia using a series of multiply affected families and report preliminary results of linkage under heterogeneity with markers on chromosome 13. A lod2 score of 1.61 for marker D13S144 was obtained at theta = 0 and alpha of 0.5 and nearby markers also produced positive values.

Adoption↗
PubMed1995

Genetic association between alleles of pancreatic phospholipase A2 gene and bipolar affective disorder.

Chromosome 12q is a region of interest for the genetics of bipolar affective disorder because of reports of apparent cosegregation between this disorder and Darier's disease in a small number of families. Findings from a recent linkage study suggest that this chromosomal region may contain a susceptibility gene for bipolar affective disorder. We have found evidence of an allelic association between bipolar disorder and a marker at the pancreatic phospholipase A2 gene (PLA2A) in this region (p < or = 0.01). These results are consistent with the linkage study, and warrant additional investigations.

Alleles↗
PubMed1995

Fluid needs in hot and cold environments.

Of all the physiological perturbations that can cause early fatigue during exercise, dehydration is arguably the most important, if only because the consequences of dehydration are potentially life threatening. The rise in body temperature that normally accompanies exercise stimulates an increase in blood flow to the skin and the onset of sweating. Normal hydration is protective of these thermoregulatory responses, whereas even a slight amount of dehydration results in measurable declines in cardiovascular and thermoregulatory function. Mild to severe dehydration commonly occurs among athletes, even when fluid is readily available. This voluntary dehydration compromises physiological function, impairs exercise performance, and increases the risk of heat illness. Recent research illustrates that maintaining normal hydration (or close to it) during exercise maintains cardiovascular and thermoregulatory responses and improves exercise performance. Consequently, it is in the athlete's best interest to adopt fluid-replacement practices that promote fluid intake in proportion to sweat loss.

Body Fluids↗
PubMed1995

Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia.

We have produced interleukin-6 (IL-6)-deficient mice to examine, in vivo, the wide variety of biological activities attributed to this multifunctional cytokine. To investigate the role of IL-6 during infectious disease, IL-6-deficient mice were challenged with sublethal doses of Listeria monocytogenes, a facultative intracellular bacterium. While normal control animals were able to clear the infection, mutant animals exhibited a high mortality rate and showed uncontrolled replication of the bacteria in the spleen and liver at 2 and 3 days postinfection. Sections of infected tissues showed an increase in the number and severity of inflammatory foci. All aspects of this phenotype in the mutant animals were completely reverted upon administration of recombinant murine IL-6 (rIL-6). Various parameters of natural killer (NK) cell and macrophage function were unaffected in the challenge of the mutant animals. However, IL-6-deficient animals failed to mount peripheral blood neutrophilia in response to listeriosis, whereas control animals displayed a prominent neutrophilia in the blood at 24 and 48 h postinfection. Additionally, we analyzed the efficacy of rIL-6 in protecting animals devoid of lymphocytes or devoid of neutrophils during listeriosis. Administration of rIL-6 was protective to animals devoid of lymphocytes, suggesting that the rIL-6 protective effect was not mediated through lymphocytes. In contrast, control and mutant animals depleted of neutrophils were refractory to the rIL-6 protective effect. These data suggest that IL-6 is critical early during listeriosis, perhaps acting by stimulating neutrophils either directly or indirectly. Additionally, these data show a promising therapeutic potential for rIL-6 administration during opportunistic infection.

Animals↗
PubMed1995

Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor.

Interleukin-6 is an essential mediator of the bone loss caused by loss of estrogens. Because loss of androgens also causes bone loss, we have examined whether the IL-6 gene is regulated by androgens, and whether IL-6 plays a role in the bone loss caused by androgen deficiency. Both testosterone and dihydrotestosterone inhibited IL-6 production by murine bone marrow-derived stromal cells. In addition, testosterone, dihydrotestosterone, and adrenal androgens inhibited the expression of a chloramphenicol acetyl transferase reporter plasmid driven by the human IL-6 promoter in HeLa cells cotransfected with an androgen receptor expression plasmid; however, these steroids were ineffective when the cells were cotransfected with an estrogen receptor expression plasmid. In accordance with the in vitro findings, orchidectomy in mice caused an increase in the replication of osteoclast progenitors in the bone marrow which could be prevented by androgen replacement or administration of an IL-6 neutralizing antibody. Moreover, bone histomorphometric analysis of trabecular bone revealed that, in contrast to IL-6 sufficient mice which exhibited increased osteoclast numbers and bone loss following orchidectomy, IL-6 deficient mice (generated by targeted gene disruption) did not. This evidence demonstrates that male sex steroids, acting through the androgen-specific receptor, inhibit the expression of the IL-6 gene; and that IL-6 mediates the upregulation of osteoclastogenesis and therefore the bone loss caused by androgen deficiency, as it does in estrogen deficiency.

Animals↗