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Biomedical subjects

R Murray

Publications and source records attributed to R Murray.

At least 145 records · Page 8Linked to original sources
PubMed1996

Dermatoglyphic a-b ridge count as a possible marker for developmental disturbance in schizophrenia: replication in two samples.

The aim of this study was to conduct an epidemiological analysis of quantitative dermatoglyphic traits as a marker of prenatal disturbance during the second trimester of life in schizophrenic patients. TFRC (Total Finger Ridge Count) and TABRC (Total a-b Ridge Count) were studied in a sample of 38 schizophrenic patients and 69 healthy individuals. A significant decrease of the a-b ridge count was found in patients compared to controls, with a significant linear trend across the population distribution (OR linear trend = 1.6; 95% CI = 1.0-2.4), indicating that the effect was not confined to a subgroup of cases with values in the lowest range. This finding was replicated in a second, larger sample (OR linear trend = 1.3; 95% CI = 1.0-1.8). The suggestion that a-b ridge count is associated with genetic risk for schizophrenia needs to be investigated further. TFRC did not distinguish between patients and controls. The a-b ridge count may be a continuous risk factor for later schizophrenia, pointing towards a disturbance occurring during the second trimester of prenatal life, a period of critical CNS growth.

Adult↗
PubMed1996

The pulmonary alveolar proteinosis in granulocyte macrophage colony-stimulating factor/interleukins 3/5 beta c receptor-deficient mice is reversed by bone marrow transplantation.

Mice mutant for granulocyte macrophage colony-stimulating factor (GM-CSF) or the common receptor component (beta c) for GM-CSF, interleukin (IL)-3, and IL-5 exhibit a lung disorder similar to human pulmonary alveolar proteinosis, a rare disease with congenital, infantile, and adult forms. Bone marrow transplantation and hematopoietic reconstitution of beta c mutant mice with wild-type bone marrow reversed the established disease state in the lungs, defining this disease as hematopoietic in nature. It is likely that the disease involves alveolar macrophages, as donor myeloid cell engraftment into the lungs of mutant recipient mice correlated with reverting both the disease and an abnormal macrophage morphology seen in the lungs of affected animals. Recombination Activating Gene-2 mutant donor bone marrow, which lacks the potential to develop lymphocytes, reversed the pathology in the lungs to the same extent as whole bone marrow. These data establish that certain lung disorders, if of cell-autonomous hematopoietic origin, can be manipulated by bone marrow transplantation.

Animals↗
PubMed1996

Post-natal lethality and neurological and gastrointestinal defects in mice with targeted disruption of the A-Raf protein kinase gene.

The Ras/Raf/MEK/MAP kinase cascade transmits signals from activated cell-surface receptors to transcription factors in the nucleus and is an essential component of metazoan intracellular signaling pathways (see, for example, [1-6]). In the mouse, the Raf protein kinase family is comprised of three homologous genes, Raf-1, A-Raf and B-Raf [5] which are ubiquitously expressed in the developing embryo [7]. We have introduced into the mouse germ line a loss-of-function mutation in the X-chromosomal A-Raf gene, by homologous recombination in embryonic stem cells. On a predominantly C57 Bl/6 genetic background, A-Raf-deficient mice displayed neurological and intestinal abnormalities and died between 7 and 21 days post-partum. When the mutated allele was maintained on a predominantly 129/OLA background, by contrast, A-Raf-deficient animals survived to adulthood, did not display obvious intestinal abnormalities, were fertile, but did have a subset of the neurological defects.

Animals↗
PubMed1996

A gene at 6p? Schizophrenia.

Schizophrenia often exhibits familial clustering; this is suggestive of heritable factors, but the whereabouts of responsible gene(s) has remained elusive. Recent research suggests that a region of chromosome 6p may hold some of the answers.

Chromosome Mapping↗
PubMed1996

A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22).

Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets (Vallada et al., Am J Med Genet 60:139-146, 1995; Polymeropoulos et al., Neuropsychiatr Genet 54:93-99, 1994; Lasseter et al., Am J Med Genet, 60:172-173, 1995. Using the affected sib-pair method as implemented by the program ESPA, the combined dataset showed 252 alleles shared compared with 188 alleles not share (chi-square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib-pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi-square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib-pair analysis was used. These results indicate that may be a susceptibility locus for schizophrenia at 22q12.

Alleles↗
PubMed1996

Life events before psychotic episodes: do clinical and social variables affect the relationship?

We have previously used data from the Camberwell Collaborative Psychosis Study to demonstrate a strong relationship between life events and subsequent episodes of schizophrenic, manic and depressive psychoses. In the current paper, we confirmed the robustness of this relationship, which was not vitiated by controlling for clinical and social variables. Thus, the event-onset association was not affected by the type of onset or the number of previous episodes. The influences of social variables, such as social class, ethnicity and marital status, did not seriously diminish the importance of events, although there may be a role for other forms of social disadvantage as reflected in these variables.

Adolescent↗
PubMed1996

Assessing the statistical power to detect linkage in a sample of 51 bipolar affective disorder pedigrees.

We used computer simulation method to address the question of power in an initial collaborative sample of 51 bipolar affective disorder pedigrees. Simulations were performed for all possible combinations using (1) two levels of diagnostic stringency, (2) three transmission models, (3) locus heterogeneity, and (4) different assumed phenocopy rates. Some of the factors affect the power to detect linkage are (1) the specification of the correct genetic model, (2) the degree of locus heterogeneity, and (3) the frequency of phenocopies. The first two assertions were supported by our simulation results, but varying the rates of phenocopy did not substantially alter the power of the sample until a critical point. However, it is important to point out that these results are dependent on the genetic models under study and on the use of the "correct" model (i.e., the one used to simulate the data). If we assume a dominant mode of inheritance and locus homogeneity, the power to detect linkage is 97.5% at a theta of .01. However, the power declines dramatically, to 60.5% and 14.7%, if only 75 and 50% of the families are linked, respectively. Locus heterogeneity has a similar effect on the power of the sample to exclude linkage. The relative lack of power in our data, in the presence of significant locus heterogeneity, and for an intermediate mode of inheritance, underscores the need for multicenter collaboration.

Adolescent↗
PubMed1996

Psychopathological syndromes in the functional psychoses: associations with course and outcome.

The aim of this study was to identify underlying dimensions of psychopathology in a cohort of patients with functional psychosis of recent onset, and to examine their prognostic value. Factor analysis of the psychopathological features of 166 consecutively admitted patients with functional psychosis of recent onset revealed seven psychopathological dimensions, which explained 63% of the variance. Five of these seven syndromes bore differential associations with subsequent treatment and illness course, independent of: (i) associations with DSM-III-R diagnosis; (ii) associations with other prognostic factors; and (iii) associations with the baseline values of outcome variables. The most striking associations were shown for an early and insidious onset syndrome with affective flattening, which predicted a more disabled course of illness on three of four outcome dimensions, and which was more common in males and unmarried individuals. A second syndrome, characterized by bizarre behaviour, inappropriate affect, catatonia, and poor rapport showed similar, slightly less striking, associations with illness course, as well as with poor pre-morbid social functioning. A third syndrome, characterized by positive psychotic symptoms was to a lesser degree associated with poorer outcome, whereas a fourth syndrome distinguished by manic symptomatology predicted a more benign illness course. A fifth syndrome identified by lack of insight predicted more time in hospital and admission under a section of the Mental Health Act during the follow-up period. A further finding was that dimensional representations of psychopathological features were considerably more useful than categorical representations (DSM-III-R and ICD-10) as predictors of illness course and treatment decisions.

Adolescent↗
PubMed1996

NK1.1+ T cells from IL-7-deficient mice have a normal distribution and selection but exhibit impaired cytokine production.

Particular subsets of T cells expressing the NK1.1 antigen have been proposed to play an immune regulatory role by their fast and strong production of cytokines, in particular IL-4. We sought to determine factors driving the functional differentiation of NK1.1+ T cells. Since NK1.1+ T cells are exquisitely sensitive to IL-7 stimulation, we analyzed the development, selection and IL-4 production of NK1.1+ T cells in IL-7-deficient mice (IL-7-/-m mice). Besides a sharp reduction of all T cell subsets, NK1.1+ T cells develop at normal relative frequencies in IL-7-/- mice. They also undergo a normal selection process, as revealed by the biased V beta TCR repertoire identical to the one in IL-7+/+ mice. However, NK1.1+ T cells from IL-7-/- mice were found to be impaired in IL-4 and IFN-gamma production in in vitro and in vivo models. In addition, IL-7 was able to restore IL-4 production by NK1.1+ thymocytes from IL-7-/- mice. Finally, IL-7 but not IL-2 or IL-4 was able to maintain and increase IL-4 production by NK1.1+ thymocytes from normal mice. These data suggest that the functional maturation of NK1.1+ T cells requires a cytokine-driven differentiation process, in which IL-7 plays a major role.

Animals↗
PubMed1996

Physiologic roles of interleukin-2, interleukin-4, and interleukin-7.

The use of gene targeting techniques has led to new insights into the physiologic function of lymphoid growth factors, their receptors, and associated signal transduction molecules in the formation and function of T and B cells. Mice rendered deficient for the growth factors interleukin-2 or interleukin-4 exhibit impairment in certain immune responses and in steady-state immune function, although production and expansion of lymphocyte populations is unaffected. In contrast, mice deficient for interleukin-7 show a severe lymphopenia in most lymphoid tissues. Interleukin-2, interleukin-4, and interleukin-7 all utilize the common gamma (gamma c) receptor component at the cell surface of lymphocytes and the Jak3 kinase molecule to transduce signals inside the cell. Both gamma c- and Jak3 kinase-deficient animals display a phenotype similar to interleukin-7-deficient animals in terms of lymphoid development. Collectively, these genetic experiments clearly define different in vivo roles for these lymphoid factors. Interleukin-2 and interleukin-4 function by influencing mature lymphocyte populations during immune responses, whereas interleukin-7 plays a singularly dominant role, in terms of the ligands that bind to the gamma c receptor, for the production and expansion of lymphocytes.

Animals↗
PubMed1996

Interleukin-6 is required for a protective immune response to systemic Escherichia coli infection.

Interleukin-6 (IL-6) is a multipotential cytokine detected in the serum of patients or experimental animals undergoing bacterial sepsis. To date, the role of IL-6 in gram-negative sepsis models has been controversial. We have used IL-6-deficient mice to investigate the role of IL-6 during virulent Escherichia coli infection and in lipopolysaccharide (LPS)-induced mortality. In this report we describe an increased susceptibility of IL-6-deficient mice to E. coli infection in terms of mortality and accumulation of viable bacteria in tissues, indicating a protective role for IL-6 during the immune response against E. coli. In contrast, mortality rates of IL-6-deficient mice and control animals undergoing LPS-induced shock did not differ, indicating that IL-6 was inconsequential for survival in this model. Furthermore, we have shown that neutrophils were crucial for resistance to E. coli in normal mice. IL-6-deficient mice were unable to efficiently induce neutrophilia in the bloodstream immediately following challenge with E. coli, in contrast to a characteristic neutrophilia induced in control animals. Prophylactic treatment of the mutant animals with recombinant IL-6 protein reverted both the deficit of neutrophilia and the accumulation of bacteria in tissues. These data clarify the role of IL-6 as protective in virulent E. coli infection and suggest that the protective effect may be at least partially mediated through neutrophils.

Animals↗
PubMed1996

Does familiality predispose to both emergence and persistence of psychosis? A follow-up study.

BACKGROUND: It as been suggested that in schizophrenia an association exists between family history of schizophrenia and poor outcome on the one hand, and family history of affective disorders and good outcome on the other. METHOD: We tested for associations between four-year outcome and familial loading for psychotic disorders in a mixed sample of 150 consecutively admitted patients with functional psychosis (schizophrenia, psychotic affective disorders, other psychotic disorders) of recent onset. For each proband, a familial loading score for (i) broadly defined psychotic disorder, (ii) schizophrenia, and (iii) affective disorder was calculated using information on relatives obtained through the Family History Research Diagnostic Criteria method and direct interviews of relatives with the Schedule for Affective Disorders and Schizophrenia. RESULTS: In our sample of psychotic patients, familial loading for psychotic disorder predicted persistent negative symptoms over the follow-up period (OR 1.5; 95% CI 1-2.2), especially in schizophrenia, and was also associated with more time hospitalised (P < 0.05) [corrected], and more social disability at follow-up (P < 0.05). Greater familial loading for schizophrenia predicted a greater likelihood of non-recovery (OR 2.2; 95% CI 1.1-4.4) and a greater likelihood to have had persistent negative symptoms over the follow-up period (OR 1.7; 95% CI 0.9-3.1). No association was found between outcome and familial loading for affective disorder. CONCLUSIONS: We conclude that familial loading may be a continuous risk factor for some dimensions of clinical outcome in the functional psychoses. This suggests that there is a continuum of genetic liability not only to the emergence of psychotic illness, but also the subsequent chronicity of the disorder.

Adolescent↗
PubMed1996

Dehydration, hyperthermia, and athletes: science and practice.

OBJECTIVE: To present the recent research that underscores the value of preventing both dehydration and hyperthermia. Such efforts will improve the athlete's capacity to perform physical activity and reduce the risk of heat-related problems. DATA SOURCES: Data were drawn from an extensive review of the scientific literature over the past 50 years with an emphasis on recent research (> 1990) that focuses on the physiological and performance benefits of fluid replacement. DATA SYNTHESIS: Even low levels of dehydration (eg, less than a 2% loss of body weight) impair cardiovascular and thermoregulatory response and reduce the capacity for exercise. Heat exposure also reduces the athlete's ability to train and compete, an effect that can be independent of hydration status. Even if athletes are well hydrated, hot weather alone will reduce their capacity to exercise. Optimal performance is possible only when dehydration and hyperthermia are minimized by ingesting ample volumes of fluid during exercise and by taking common-sense precautions in keeping cool. Recent research has demonstrated that consuming fluid in volumes approximating sweat loss maintains important physiological functions and significantly improves exercise performance, even during exercise lasting only 1 hour. Carbohydrate ingestion also improves exercise performance, an effect that is independent of, and additive to, preventing dehydration. CONCLUSION/APPLICATION: Athletes should follow an aggressive fluid replacement and temperature regulation regimen. Successful implementation of this regimen requires that athletic trainers, coaches, athletes, and support personnel are made aware of the benefits of adequate fluid replacement, that appropriate fluid replacement strategies are developed and implemented, that athletes have the opportunity to train themselves to ingest larger volumes of fluid more frequently, and that other practical steps are taken to keep athletes cool during both training and competition.

Journal Article↗
PubMed1996

Advances in the treatment of schizophrenia.

We review advances in the treatment of schizophrenia. We begin with an overview of antipsychotic drug development, focusing on the in vitro and in vivo binding profiles of clozapine and a new generation of D2:5HT antagonists. We then consider the main barriers to effective treatment: non-compliance (and side-effects) of medication, recurrent relapse, 'treatment resistance', negative symptoms and neurocognitive deficits. Within this framework, we review the mechanisms of action and clinical uses of the 'atypical' antipsychotic drugs. We also show how a variety of psychosocial interventions, particularly those that incorporate cognitive techniques, can be used in combination with pharmacotherapy to overcome the same clinical hurdles.

Antipsychotic Agents↗
PubMed1995

Neuroticism: a vulnerability marker for depression evidence from a family study.

INTRODUCTION: We investigated the relationship between depressive illness and personality traits from the Eysenck Personality Inventory (EPI) using data from a family study. METHODS: The first-degree relatives of a series of 89 probands with RDC major depression (MD) were subdivided by their lifetime RDC diagnosis into: (1) relatives recovered from MD (n = 34); (2) never-ill relatives (n = 45). The neuroticism (N) and extraversion (E) scores of these two groups were compared using a multilevel linear model, allowing for potential confounders. The relationship between age of onset and recurrence of MD and N scores in group 1 was also examined. RESULTS: (1) Raised N scores were associated with a past history of major depression. (2) There was no such relationship for E scores. (3) Current depressive symptoms were also associated with an increased N score but this did not explain the relationship between previous major depression and N scores. (4) Recurrent episodes of major depression in the recovered MD relatives were significantly associated with increased N scores. CONCLUSION: These data suggest that raised N may be a vulnerability marker for major depression.

Adult↗
PubMed1995

Psychosis with good prognosis in Afro-Caribbean people now living in the United Kingdom.

OBJECTIVES: To compare the course and outcome of psychotic illness in a group of Afro-Caribbean patients resident in the United Kingdom and a group of white British patients. DESIGN: Cohort study of consecutive admissions followed up for four years. SUBJECTS: 113 patients with psychotic illness of recent onset admitted to two south London hospitals. MAIN OUTCOME MEASURES: Course of illness, history of self harm, social disability, treatment received, and hospital use adjusted for socioeconomic origin. RESULTS: The Afro-Caribbean group spent more time in a recovered state during the follow up period (adjusted odds ratio 5.0; 95% confidence interval 1.7 to 14.5), were less likely to have had a continuous illness (0.3; 0.1 to 0.8), were less at risk of self harm (0.2; 0.1 to 0.8), and were less likely to have been prescribed antidepressant treatment (0.3; 0.1 to 0.9). There were no differences in hospital use, but the Afro-Caribbean group had more involuntary admissions (8.9; 2.1 to 35.6) and more imprisonments over the follow up period (9.2; 1.6 to 52.3). CONCLUSIONS: Afro-Caribbean patients in the United Kingdom have a better outcome after psychiatric illness than do white people. The combination of high incidence and more benign course of illness of psychotic illness in this group may be due, at least in part, to a greater exposure to precipitants in the social environment.

Adolescent↗