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R Murray

Publications and source records attributed to R Murray.

At least 109 records · Page 6Linked to original sources
PubMed1998

Brain changes in schizophrenia. Volumetric MRI study of families multiply affected with schizophrenia--the Maudsley Family Study 5.

BACKGROUND: Structural brain abnormalities have been reported in schizophrenia. We tested the hypothesis that these abnormalities represented a marker for the genetic liability to schizophrenia in a sample of people with schizophrenia and their relatives from families multiply affected with the disorder. METHOD: We compared 31 people with schizophrenia, 57 relatives and 39 unrelated control subjects. Volumetric measurement of brain structures was carried out using stereological principles from three-dimensional reconstructed magnetic resonance images. RESULTS: Subjects with schizophrenia had larger lateral ventricles than their relatives and the normal control subjects. Relatives who were 'presumed obligate carriers' had larger left lateral ventricles than other relatives and the control subjects. Subjects with schizophrenia showed smaller whole brain and cerebellar volumes and larger lateral ventricles than their age- and gender-matched unaffected siblings. CONCLUSIONS: In families multiply affected with schizophrenia lateral ventricular enlargement distinguishes people with schizophrenia and presumed obligate carriers from other relatives and unrelated control subjects. These changes may be a marker for a genetic liability to schizophrenia.

Adult↗
PubMed1998

Family history as a predictor of poor long-term outcome in depression.

BACKGROUND: We investigated whether family history had prognostic significance in depression in a study which addressed some of the methodological shortcomings of previous studies. METHOD: We collected family history data on a consecutive series of 89 patients admitted with RDC major depression, blind to the outcome of the proband. This comprised 116, 283 and 120 first-degree relatives examined with the SADS-L, FH-RDC and case note data, respectively. The outcome of 74 of these probands (83%), previously categorised into four operationally defined groups, was then examined. RESULTS: A positive family history of severe psychiatric illness (i.e. a relative with a history of either a psychosis, hospitalised depression or suicide) was associated with poor outcome in the proband. This association persisted after controlling for variable family size, age structure and gender. As family history was correlated with neither Kendell's neurotic/psychotic index nor the proband's neuroticism score, an individual with high scores an all three would have a greatly increased chance of having a poor outcome. CONCLUSIONS: A family history of severe psychiatric illness in a first-degree relative may be useful as one of the vulnerability factors for predicting poor long-term outcome in depression.

Adolescent↗
PubMed1998

Special feature: childhood personality characteristics of schizophrenia: manifestations of, or risk factors for, the disorder?

Many retrospective studies, and an increasing number of prospective studies, have identified subtle abnormalities in preschizophrenics from as early as the first year of life. Premorbid characteristics include development delays, cognitive deficits, and abnormal social interactions. Schizoid personality traits have been a particularly well documented finding, and show some specificity in their association with schizophrenia. Information about the premorbid characteristics of schizophrenia has played a major role in the reorientation of the field, from regarding schizophrenia as an adult onset degenerative disorder, to considering it, at least in part, as a neurodevelopmental condition. However, whether the childhood personality traits are a reflection of an underlying brain lesion, or whether they are independent risk factors for the disorder, is uncertain. In the future, the identification of childhood characteristics may enable us to predict those who are at high risk of developing schizophrenia, and may even be useful in formulating preventive policies. However, at present, the powers of prediction are inadequate for such purposes.

Adult↗
PubMed1998

Interleukin-17.

The particular interest of IL-17, a homodimeric cytokine of about 32 kDa, is the strict requirement for an activation signal to induce its expression from a rather restricted set of cells, human memory T cells or mouse alpha beta TCR+CD4-CD8- thymocytes. In contrast with the tightly controlled expression pattern of this gene, the IL-17 receptor, a novel cytokine receptor, is ubiquitously distributed but apparently more abundant in spleen and kidney. In addition to its capture by the T lymphotropic Herpesvirus Saimiri (HVS), this cytokine is inducing the secretion of IL-6, IL-8, PGE2, MCP-1 and G-CSF by adherent cells like fibroblasts, keratinocytes, epithelial and endothelial cells. IL-17 is also able to induce ICAM-1 surface expression, proliferation of T cells, and growth and differentiation of CD34+ human progenitors into neutrophils when cocultured in presence of irradiated fibroblasts. In vitro, IL-17 synergizes with other proinflammatory signals like TNF alpha for GM-CSF induction, and with CD40-ligand for IL-6, IL-8, RANTES and MCP-1 secretion from kidney epithelial cells. In vivo, injection of IL-17 induces a neutrophilia, except in IL-6-KO mice. The involvement of IL-17 in rejection of kidney graft has also been demonstrated. The role of this T cell secreted factor in various inflammatory processes is presently investigated.

Animals↗
PubMed1998

Discharged residents' satisfaction with transitional housing for the homeless.

One year following discharge from a transitional residential program, homeless women, some of whom were chemically dependent or mentally ill, indicated that they were satisfied with the program and that it had met their needs. Suggestions for improvement related primarily to greater flexibility of rules in the transitional residence. Most of the women had improved their housing situation since discharge; all of the women continued to maintain a home for their children.

Adult↗
PubMed1998

Augmentation of Pap smear screening of high risk aboriginal women. Use of a computerised process tool within the Broome Aboriginal Medical Service.

OBJECTIVE: The Broome Regional Aboriginal Medical Service (BRAMS) in Broome, Western Australia, conducted a 4 month program to augment the Pap smear screening of Aboriginal women. The emphasis was on those with a past history of abnormal smears, aged greater than 40 years, living in remote communities and very (more than 5 years) overdue. METHOD: Continuation of existing opportunistic recall processes supplemented by three components: the development of an Aboriginal Health Worker (AHW) run Pap smear clinic; the provision of Aboriginal outstation screening; and active recruitment of targeted women (by AHW staff) using worklists. All components used Healthplanner, a computerised process tool to facilitate targeting and recall. MAIN OUTCOME MEASURES: The number of Pap smears taken from the target groups before and after intervention and the proportion screened from the women eligible in each target group at the start of the program. RESULTS: There was statistically significant increase in the coverage of Aboriginal women overall, those over the age of 40 years, and those from remote communities when compared with the same period the previous years. In 4 months, 21-30% of Aboriginal women eligible for Pap smears in these high risk categories including those with past abnormal smears were screened. Over-screening of women did not occur as only 4% of smears taken were from women screened less than 12 months previously. Smears taken by AHW staff were of high quality. CONCLUSION: Use of a computerised process tool in a remote setting can facilitate selective recruitment of high risk women overdue for Pap smears.

Adult↗
PubMed1997

Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression.

Pulmonary alveolar proteinosis (PAP) is a heterogeneous disorder of genetic or acquired etiologies. In some cases congenital PAP is associated with hereditary surfactant protein (SP)-B deficiency. To date, the molecular defect in the majority of patients with PAP has not been identified. In mice, PAP has been generated by targeted deletion of the genes for either the GM-CSF/IL-3/IL-5 receptor common beta chain (beta c) or GM-CSF. Here, we describe an expression defect of beta c in three of seven pediatric patients with PAP and in one patient with severe lung disease suspected to be PAP. The patients failed to express normal levels of beta c as shown by flow cytometry. Strikingly reduced or absent function of beta c was demonstrated by ligand binding studies and progenitor clonogenic assays. Analysis of beta c DNA revealed a point mutation from proline to threonine at codon 602 in one patient. Our findings provide evidence that a defect in the expression of a hematopoietic cytokine receptor is associated with human PAP.

Adult↗
PubMed1997

HNMP-1: a novel hematopoietic and neural membrane protein differentially regulated in neural development and injury.

The hnmp-1 (hematopoietic neural membrane protein) gene encodes a protein with striking similarity to the tetra-transmembrane-spanning protein encoded by pmp22. hnmp-1 was cloned from an elutriated human monocyte library and is expressed in various human hematopoietic and lymphoid lineages as well as adult mouse spleen and thymus. In the mouse nervous system, HNMP-1 mRNA is temporally expressed by Schwann cells during sciatic nerve myelination. Dorsal root ganglia sensory and spinal cord alpha-motoneurons acquire HNMP-1 protein selectively throughout development. In the fiber tracts of the spinal cord and in sciatic nerve, HNMP-1 protein is axon-associated. Additionally a rapid and sustained level of HNMP-1 expression is observed in response to acute PNS injury. HNMP-1 is constituitively induced in sciatic nerve of Trembler J mice, which are mutant for pmp22 and have a demyelinating/hypomyelinating phenotype. The expression pattern of HNMP-1 suggests a possible role for this molecule during active myelination.

Amino Acid Sequence↗
PubMed1997

Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice.

Mice lacking functional IL-7 or IL-7R alpha genes are severely deficient in developing thymocytes, T cells, and B cells. IL-7 and IL-7 receptor functions are believed to result in lymphoid cell proliferation and cell maturation, implying signal transduction pathways directly involved in mitogenesis and elaboration of developmentally specific new gene programs. Here, we show that enforced expression of the bcl-2 gene in T-lymphoid cells (by crossing in the Emu-bcl-2 transgene) in IL-7R alpha-deficient mice results in a significant restoration of thymic positive selection and T cell numbers and function. We propose cell survival signals to be the principal function of IL-7R engagement in thymic and T cell development.

Animals↗
PubMed1997

5-HT2A receptor and bipolar affective disorder: association studies in affected patients.

The aim of this study was to investigate the possible involvement of genetic variation in serotonin receptors in the aetiology of bipolar affective disorder. The 5-HT2A receptor gene was systematically screened for genetic variants by single strand conformation polymorphism (SSCP) methods in subjects with bipolar affective disorder. Four polymorphisms (two structural changes, Thr25Asn and His4 M52Tyr, and two silent polymorphisms, 102-T/C and 516-C/T) which had previously been found in patients with schizophrenia and control subjects were detected. No novel polymorphisms were found in patients with bipolar affective disorder. These polymorphisms were genotyped in a sample of 129 patients and 252 controls of German origin and 176 patients and 182 controls of British origin. No strong associations were found between any of these polymorphisms and bipolar affective disorder. Genetic variation at the 5-HT2A receptor gene does not play a major role in the pathogenesis of the disorder.

Alleles↗
PubMed1997

Developmental precursors of affective illness in a general population birth cohort.

BACKGROUND: Recent evidence suggests that neurodevelopmental impairment may be a risk factor for later affective disorder. METHODS: Associations between childhood developmental characteristics and affective disorder were examined in a prospectively studied national British birth cohort of 5362 individuals born between March 3 and March 9, 1946. Mental state examinations by trained interviewers performed at ages 36 and 43 years identified 270 case subjects with adult affective disorder (AD). Teachers' questionnaires completed at age 13 and 15 years identified 195 case subjects who had shown evidence of childhood affective disturbance (CAD). RESULTS: Female gender and low educational test scores at ages 8, 11, and 15 years were a risk factor for AD, CAD, and AD without CAD. In addition, attainment of motor milestones was later in the CAD group (odds ratio [OR] = 1.2; 95% confidence interval [CI], 1.1-1.3), followed by, and independent of, greater risk for speech defects between the ages of 6 and 15 years (OR = 2.0; 95% CI, 1.3-3.0), decreased psychomotor alertness on medical examination between ages 4 and 11 years (OR = 4.6; 95% CI, 2.2-9.7), and an excess of twitching and grimacing motor behaviors in adolescence (OR = 3.9; 95% CI, 2.5-6.1). Persistent CAD was strongly associated with persistent AD (OR = 7.8; 95% CI, 2.6-23.2). CONCLUSION: The findings give credence to the suggestion that affective disorder, especially its early-onset form, is preceded by impaired neurodevelopment.

Adolescent↗
PubMed1997

Suggestive evidence for linkage of schizophrenia to markers on chromosome 13 in Caucasian but not Oriental populations.

Previously we reported suggestive evidence for linkage of schizophrenia to markers on chromosome 13q14.1-q32. We have now studied an additional independent sample of 44 pedigrees consisting of 34 Taiwanese, 9 English and 1 Welsh family in an attempt to replicate this finding. Narrow and broad models based on Research Diagnostic Criteria or the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, were used to define the schizophrenia phenotype. Under a dominant genetic model, two-point lod scores obtained for most of the markers were negative except that marker D13S122 gave a total lod score of 1.06 (theta = 0.2, broad model). As combining pedigrees from different ethnic origins may be inappropriate, we combined this replication sample and our original sample, and then divided the total sample into Caucasian (English and Welsh pedigrees) and Oriental (Taiwanese and Japanese pedigrees) groups. The Caucasian pedigrees produced maximized admixture two-point lod scores (A-lod) of 1.41 for the marker D13S119 (theta = 0.2, alpha = 1.0) and 1.54 for D13S128 (theta = 0, alpha = 0.3) with nearby markers also producing positive A-lod scores. When five-point model-free linkage analysis was applied to the Caucasian sample, a maximum lod score of 2.58 was obtained around the markers D13S122 and D13S128, which are located on chromosome 13q32. The linkage results for the Oriental group were less positive than the Caucasian group. Our results again suggest that there is a potential susceptibility locus for schizophrenia on chromosome 13q14.1-q32, especially in the Caucasian population.

Asian People↗
PubMed1997

The Maudsley Family Study. I: Structural brain changes on magnetic resonance imaging in familial schizophrenia.

1. The authors investigated the prevalence of qualitatively rated structural brain abnormalities in schizophrenic probands and their first-degree relatives from families multiply affected with schizophrenia. 2. Magnetic resonance imaging was used to evaluate brain morphology in 33 schizophrenic probands, 54 of their non-schizophrenic first-degree relatives (including 11 presumed obligate carriers) and 37 unrelated control subjects. Structural images were examined by a neuroradiologist who was blind to diagnostic and family status. 3. 52% of the schizophrenic subjects were rated as showing abnormalities compared with 27% of presumed obligate carriers, 16% of their non-schizophrenic relatives and 11% of unrelated controls. 4. Brain abnormalities were more frequent in schizophrenic subjects from multiplex families than in their first-degree relatives and controls. Abnormalities were also found in unaffected relatives particularly those who appear to be transmitting the disorder.

Adult↗
PubMed1997

Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimide: a phase II multicentre multinational study. Exemestane Study Group.

In a European multicentre phase II study, 80 postmenopausal patients (pts) with advanced breast cancer progressing on aminoglutethimide (AG) at daily doses of > or = 500 mg were enrolled. Seventy-eight received exemestane (200 mg daily orally), including 33 pts resistant to prior AG, 39 pts who had progressed after an initial response to AG, and 6 pts whose response to AG was either unavailable or not evaluable. Three pts were pretreated with AG only, 69 with tamoxifen and AG, and 6 with tamoxifen, AG and other hormone therapies; 55% had also previously received chemotherapy. The predominant site of disease was visceral in 34 cases, bone in 27 and soft tissue in 17. Based on Peer Review assessment, the overall objective response rate (CRs plus PRs) was 26% (12% in pts resistant to AG and 33% in AG-responsive pts). Disease stabilisation > or = 24 weeks was achieved in an additional 13% of patients (15% of those resistant to AG and 13% of those AG-responsive), resulting in an overall success rate of 39% (28-50, 95% confidence interval). The median duration of objective response, overall success and median TTP were 59, 48 and 21 weeks, respectively. Toxicities were usually mild to moderate in severity, with hot flushes (21%), nausea (19%), dizziness (12%), weakness (12%), increased sweating (12%), androgenic symptoms (10%) and peripheral oedema (9%) as the most common side-effects. Only 2 pts (3%) discontinued treatment due to adverse events. These results are very promising considering that exemestane was administered as third- or fourth-line hormonal treatment in most cases and confirm previous observations about the lack of cross-resistance when steroidal aromatase inhibitors are sequenced with the non-steroidal aromatase inhibitor AG.

Aged↗
PubMed1997

Induction of TCR gene rearrangements in uncommitted stem cells by a subset of IL-7 producing, MHC class-II-expressing thymic stromal cells.

The embryonic thymic microenvironment provides the necessary elements for T cell lineage commitment, but the precise role of individual stromal cell components remains to be determined. Here we address the question of which stromal cell types are required for initiation of V-DJ rearrangements of the TCR-beta and TCR-delta locus in CD117+CD45+ uncommitted fetal liver progenitors. We show that fetal thymic stroma alone is necessary and sufficient for induction of TCR-beta and TCR-delta rearrangements. Furthermore, the ability to induce this T cell commitment step is confined to a subset of MHC class II-positive epithelial cells. Thymic stroma derived from mice with a targeted deletion in the IL-7 gene, however, lacks this ability. These findings set the stage for a further definition of the nature of the thymic stromal cell support in the regulation of T cell commitment.

Animals↗
PubMed1997

The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression.

Interleukin-7 (IL-7)-deficient mice exhibit an early defect in lymphopoiesis. We examined Bcl-2 expression and the cell cycle status of immature thymocyte subsets in these mice. In IL-7-deficient mice, developmental transition to a T cell-committed fate was accompanied by a striking loss of Bcl-2 protein expression and an increased relative proportion of cells in the G0/G1 stage of the cell cycle. Short-term culture of immature thymocytes with rIL-7 caused up-regulation of Bcl-2 protein and cell survival. These data specify a T cell lineage developmental transition point, prior to T cell antigen receptor rearrangement, where IL-7 signal transduction is linked to an anti-apoptosis mechanism and the cell cycle.

Animals↗