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R Murray

Publications and source records attributed to R Murray.

At least 37 records · Page 2Linked to original sources
PubMed2000

Children's self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study.

BACKGROUND: Childhood risk factors for the development of adult schizophrenia have proved to have only modest and nonspecific effects, and most seem unrelated to the adult phenotype. We report the first direct examination of the longitudinal relationship between psychotic symptoms in childhood and adulthood. METHODS: We analyzed prospective data from a birth cohort (N = 761), in which children were asked about delusional beliefs and hallucinatory experiences at age 11 years, and then followed up to age 26 years. Structured diagnostic interviews were employed at both ages and self-report of schizophreniform symptoms was augmented by other data sources at age 26 years. RESULTS: Self-reported psychotic symptoms at age 11 years predicted a very high risk of a schizophreniform diagnosis at age 26 years (odds ratio, 16.4; 95% confidence interval, 3.9-67.8). In terms of attributable risk, 42% of the age-26 schizophreniform cases in the cohort had reported 1 or more psychotic symptoms at age 11 years. Age-11 psychotic symptoms did not predict mania or depression at age 26 years, suggesting specificity of prediction to schizophreniform disorder. The link between child and adult psychotic symptoms was not simply the result of general childhood psychopathology. CONCLUSION: These findings provide the first evidence for continuity of psychotic symptoms from childhood to adulthood.

Adolescent↗
PubMed2000

Impact of beverage acceptability on fluid intake during exercise.

These two studies investigated the impact of beverage acceptability on voluntary fluid intake during exercise and the subsequent impact of exercise on the perception and liking of beverages. In Experiment 1, 49 triathletes and runners first tasted an array of 10 commercially available flavors of a 6% carbohydrate-electrolyte drink (CE) and water (W) to determine the most-acceptable flavor (M) and least-acceptable flavor (L) for each subject. Subjects were subsequently given M, L, or W ad libitum during 180 min of exercise. Drink acceptability was again measured after 90 and 180 min of exercise. Drink intake was measured at 15-min intervals. Intake of M was significantly greater than L and W throughout the first 75 min and significantly greater than W throughout the entire exercise period. In Experiment 2, subjects were given M+W, or L+W, in a two-bottle procedure. Voluntary intake of M and L exceeded W by 318% and 233%, respectively. An unexpected finding was a strong interaction between drink acceptability and exercise state. The acceptability of L increased substantially from sedentary to exercise conditions. These data demonstrated that the flavored, sweetened beverages used in this study, substantially increased voluntary fluid intake over W.

Adult↗
PubMed2000

Diagnostic value of the DSM and ICD categories of psychosis: an evidence-based approach. UK700 Group.

BACKGROUND: It is generally assumed that the distinction between affective and non-affective psychosis occasioned by modern diagnostic criteria provides a useful symptomatic contrast. METHOD: In a sample of 708 patients with chronic psychosis, the distinction of lifetime DSM-III-R and ICD-10 diagnoses of affective versus non-affective psychosis was used as a diagnostic test to detect lifetime presence of depressive, manic, positive, negative and disorganisation symptoms. RESULTS: A manic or depressive affective diagnosis was a perfect test to diagnose the presence of manic and depressive symptoms, as evidenced by very high diagnostic likelihood ratios. However, this test result was based solely on the inclusion criterion that patients with affective psychosis must have affective symptoms (guaranteeing high specificity and high likelihood ratios), and ignored the fact that patients with non-affective psychosis also had high affective symptom scores (low sensitivity). Furthermore, a non-affective psychotic diagnosis was a very poor test to diagnose correctly the presence of positive, negative and disorganisation symptoms in comparison with an affective psychotic diagnosis. In general, the DSM-III-R categories performed somewhat better as a diagnostic test than those of ICD-10. CONCLUSION: The evidence for true diagnostic value of the distinction between affective and non-affective psychotic diagnoses is weak. Rather, the distinction appears to obscure natural overlap between the symptom dimensions of the different diagnostic categories.

Adolescent↗
PubMed2000

DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming.

DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activation of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, although the activating Ly49 receptors on NK cells were downregulated and nonfunctional. To analyze the consequences of DAP12 deficiency in vivo, we examined the susceptibility of DAP12-/- mice to experimental autoimmune encephalomyelitis (EAE). DAP12-/- mice were resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance was associated with a strongly diminished production of IFNgamma by myelin-reactive CD4+ T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Association analysis of the GABA(A) receptor subunit genes cluster on 5q33-34 and alcohol dependence in a Japanese population.

Recent investigations suggest that genetic susceptibility to alcohol dependence may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2 receptor subunit genes, were examined for association with alcohol dependence in 189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated controls from a Japanese population. The results demonstrated no association between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor subunit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P = 0.021). This supports a recent finding reporting an association between the GABA(A)gamma2 receptor subunit gene and alcohol dependence with criminal record in a Finnish population. Taking into account the effects of multiple comparisons, this result should be interpreted with caution pending replication.

Adult↗
PubMed2000

A fission yeast homolog of Int-6, the mammalian oncoprotein and eIF3 subunit, induces drug resistance when overexpressed.

Through a screen to identify genes that induce multi-drug resistance when overexpressed, we have identified a fission yeast homolog of Int-6, a component of the human translation initiation factor eIF3. Disruption of the murine Int-6 gene by mouse mammary tumor virus (MMTV) has been implicated previously in tumorigenesis, although the underlying mechanism is not yet understood. Fission yeast Int6 was shown to interact with other presumptive components of eIF3 in vivo, and was present in size fractions consistent with its incorporation into a 43S translation preinitiation complex. Drug resistance induced by Int6 overexpression was dependent on the AP-1 transcription factor Pap1, and was associated with increased abundance of Pap1-responsive mRNAs, but not with Pap1 relocalization. Fission yeast cells lacking the int6 gene grew slowly. This growth retardation could be corrected by the expression of full length Int6 of fission yeast or human origin, or by a C-terminal fragment of the fission yeast protein that also conferred drug resistance, but not by truncated human Int-6 proteins corresponding to the predicted products of MMTV-disrupted murine alleles. Studies in fission yeast may therefore help to explain the ways in which Int-6 function can be perturbed during MMTV-induced mammary tumorigenesis.

Amino Acid Sequence↗
PubMed2000

Gastric emptying of cold beverages in humans: effect of transportable carbohydrates.

Eight healthy subjects, aged 39.0 ¿ 2.4 years, consumed four 6% carbohydrate-electrolyte solutions containing either one (glucose or fructose) or two transportable carbohydrates in single (glucose + fructose) or bound (sucrose) forms. Solution osmolalities ranged from 250 to 434 mOsm/kg H2O. The test solutions were ingested at rest in the amount of 6 ml/kg of body weight at a temperature of 12 ¿C. Gastric emptying rate was measured by repeated aspirations via a nasogastric tube using the modified George double-sampling technique. The intragastric temperature was determined by a temperature probe attached to the nasogastric tube. There were no significant differences in gastric emptying rates and gastric volumes among the solutions. Intragastric temperature dropped from 36.5 ¿C to 23.3 ¿ 3 ¿C immediately after beverage ingestion but recovered to above 30 ¿C within 5 min. These data suggest that the gastric emptying rate of the specified beverages is not affected by the number and type of carbohydrates or by solution osmolalities within the tested range. Within 5 min after ingestion, cold beverages are warmed to above 30 C in the stomach. This infers that the effect of cold solution temperature on gastric emptying rate is likely to be small and transitory.

Adult↗
PubMed2000

Protective immunity to rotavirus shedding in the absence of interleukin-6: Th1 cells and immunoglobulin A develop normally.

We investigated whether interleukin-6 (IL-6) was required for the development of immunoglobulin A (IgA)- and T-helper 1 (Th1)-associated protective immune responses to rotavirus by using adult IL-6-deficient mice [BALB/c and (C57BL/6 x O1a)F(2) backgrounds]. Naive IL-6(-) mice had normal frequencies of IgA plasma cells in the gastrointestinal tract. Consistent with this, total levels of IgA in fecal extracts, saliva, and sera were unaltered. In specific response to oral infection with rhesus rotavirus, IL-6(-) and IL-6(+) mice exhibited efficient Th1-type gamma interferon responses in Peyer's patches with high levels of serum IgG2a and intestinal IgA. Although there was an increase in Th2-type IL-4 in CD4(+) T cells from IL-6(-) mice following restimulation with rotavirus antigen in the presence of irradiated antigen-presenting cells, unfractionated Peyer's patch cells failed to produce a significant increase in IL-4. Moreover, virus-specific IgG1 in serum was not significantly increased in IL-6(-) mice in comparison with IL-6(+) mice. Following oral inoculation with murine rotavirus, IL-6(-) and IL-6(+) mice mediated clearance of rotavirus and mounted a strong IgA response. When IL-6(-) and IL-6(+) mice [(C57BL/6 x O1a)F(2) background] were orally inoculated with rhesus rotavirus and later challenged with murine rotavirus, all of the mice maintained high levels of IgA in feces and were protected against reinfection. Thus, IL-6 failed to provide unique functions in the development of IgA-secreting B cells and in the establishment of Th1-associated protective immunity against rotavirus infection in adult mice.

Animals↗
PubMed2000

Inhibition of T lymphocyte activation in mice heterozygous for loss of the IMPDH II gene.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in the de novo synthesis of guanine nucleotides, which are also synthesized from guanine by a salvage reaction catalyzed by the X chromosome-linked enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Since inhibitors of IMPDH are in clinical use as immunosuppressive agents, we have examined the consequences of knocking out the IMPDH type II enzyme by gene targeting in a mouse model. Loss of both alleles of the gene encoding this enzyme results in very early embryonic lethality despite the presence of IMPDH type I and HPRT activities. Lymphocytes from IMPDH II(+/-) heterozygous mice are normal with respect to subpopulation distribution and respond normally to a variety of mitogenic stimuli. However, mice with an IMPDH II(+/-), HPRT(-/o) genotype demonstrate significantly decreased lymphocyte responsiveness to stimulation with anti-CD3 and anti-CD28 antibodies and show a 30% mean reduction in GTP levels in lymphocytes activated by these antibodies. Furthermore, the cytolytic activity of their T cells against allogeneic target cells is significantly impaired. These results demonstrate that a moderate decrease in the ability of murine lymphocytes to synthesize guanine nucleotides during stimulation results in significant impairment in T-cell activation and function.

Animals↗
PubMed2000

Functional anatomy of auditory verbal imagery in schizophrenic patients with auditory hallucinations.

OBJECTIVE: This study investigated the functional neuroanatomy of inner speech and auditory verbal imagery in schizophrenic patients predisposed to auditory hallucinations. METHOD: Eight patients with schizophrenia with a history of prominent auditory hallucinations and six comparison subjects underwent functional magnetic resonance imaging while generating inner speech or imagining external speech. RESULTS: Patients showed no differences while generating inner speech but experienced a relatively attenuated response in the posterior cerebellar cortex, hippocampi, and lenticular nuclei bilaterally and the right thalamus, middle and superior temporal cortex, and left nucleus accumbens during auditory verbal imagery. CONCLUSIONS: Patients with schizophrenia who were prone to auditory hallucinations show attenuated activation when processing inner speech in areas implicated in verbal self-monitoring.

Adult↗
PubMed2000

Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial.

PURPOSE: To evaluate the antitumor activity and toxicity of a new steroidal aromatase inactivator, exemestane, in postmenopausal women with metastatic breast cancer who had progressive disease (PD) after treatment with a nonsteroidal aromatase inhibitor. PATIENTS AND METHODS: In this phase II trial, eligible patients were treated with exemestane 25 mg daily (n = 241) followed, at the time PD was determined, by exemestane 100 mg daily (n = 58). RESULTS: On the basis of the intent-to-treat analysis by independent review, exemestane 25 mg produced objective responses in 6.6% of patients (95% confidence interval [CI], 3.8% to 10.6%) and overall success (complete response + partial response + no change for 24 weeks or longer) in 24.3% (95% CI, 19.0% to 30.2%). The median durations of objective response and overall success were 58.4 weeks (95% CI, 49.7 to 71.1 weeks) and 37.0 weeks (95% CI, 35.0 to 39.4 weeks), respectively. Increasing the dose of exemestane to 100 mg upon the development of PD produced one partial response (1.7%; 95% CI, 0.0% to 9.2%). Both dosages were well tolerated and were discontinued because of adverse events in only 1.7% of patients. CONCLUSION: Exemestane 25 mg once daily seems to be an attractive alternative to chemotherapy for the treatment of patients with metastatic breast cancer after multiple hormonal therapies have failed.

Administration, Oral↗
PubMed2000

[Lack of gender effect on familial schizophrenia. A Brazilian study].

Epidemiological studies on schizophrenia have showed different age at onset between gender, in which male schizophrenics present symptoms earlier than females. However this gender effect is not observed within familial schizophrenia. The present study investigates the age at onset in 31 RDC-schizophrenics from 13 Brazilian families. No differences in age at onset were found between gender, confirming previous studies in other populations. This result may indicate genetic influences on age at onset in a subgroup of patients affected by schizophrenia and can be explored by molecular genetic studies.

Adolescent↗
PubMed2000

The doctor and the rebels--the diary of Charles Molteno Murray, recorded during the 1914 Boer rebellion.

Just 12 years after the conclusion of the Anglo-Boer war, South Africa was led by ex-Boer Generals Botha and Smuts into what was to become the Great War, on the side of the British. This was utterly unacceptable to thousands of Boers who had engaged in a bitter struggle, against overwhelming odds, to prevent their country from becoming part of the mighty British Empire. Led by Generals de Wet, Beyers, and de la Rey, Lieutenant-Colonel Maritz and Major Kemp, they took up arms in a doomed rebellion, without proper weapons, equipment or organisation--by the time they were defeated the casualty figures for both sides exceeded those that would later result from the German South West campaign. Charles Molteno Murray, 37 years old, was a GP in Kenilworth, Cape Town, at the time. His father was an Irish immigrant doctor, his mother the daughter of the first Prime Minister of the Cape, Sir John Charles Molteno. In spite of having a busy and successful practice, with a surgical appointment at Victoria Hospital, Charles Murray volunteered for duty and soon found himself in the Orange Free State and northern Cape, caring for the wounded and dying of both sides in the rebellion. He kept a meticulous record of his experiences, written on loose-leaf pages sent as letters to his wife, which were later bound into leather-backed diaries. These diaries were passed on to his grandson, Dr Robert Murray, who had them transcribed into modern format. They contain details of daily life in the midst of military action, and also insights into important and little-publicised events of the Boer Rebellion of 1914.

History, 20th Century↗
PubMed1999

Lack of normal pattern of cerebral asymmetry in familial schizophrenic patients and their relatives--The Maudsley Family Study.

Lack of the normal cerebral asymmetry has been reported in schizophrenia. We wished to test the hypothesis that this lack of the normal pattern of asymmetry is familial and that it can be found in both schizophrenic and non-schizophrenic family members. In particular, we wanted to know whether those relatives who appear to be transmitting liability to the illness also demonstrate the loss of normal asymmetry. We studied families with several members affected with schizophrenia. We carried out volumetric measurements of prefrontal, premotor, sensorimotor and occipitoparietal regions in each hemisphere using 3D reconstructed MRI images in 29 schizophrenic patients, 55 of their first degree relatives, and 39 unrelated control subjects on contiguous thin slices of the brain. Nine of the unaffected relatives appeared to be transmitting the liability for schizophrenia (e.g. the mother of a schizophrenic patient who, although not psychotic herself, had a schizophrenic parent or sibling). We termed them presumed obligate carriers and the remaining 46 relatives presumed non-obligate carriers. The healthy control subjects showed larger right than left prefrontal regions and larger left than right sensorimotor and occipitoparietal regions. The schizophrenic patients showed lack of this normal brain asymmetry in the prefrontal, sensorimotor and occipitoparietal cortical regions. The presumed obligate carriers were similar to the schizophrenic patients in exhibiting lack of asymmetries in these cortical regions, while the presumed non-obligate relatives showed lack of asymmetry only in the occipitoparietal region. There was no overall reduction in total or regional brain volumes among the groups. Our findings indicate that lack of the normal pattern of frontal and occipital asymmetry is a marker for genetic liability to schizophrenia in families multiply affected with schizophrenia.

Adult↗
PubMed1999

Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications.

BACKGROUND: Hippocampal volume reduction has been repeatedly demonstrated in schizophrenia. The relative contribution of genetic and environmental factors to this is unclear. METHODS: To address this question, we compared volumetric measurements of the left and right hippocampus, obtained using stereological methods from brain MRI scans, from two groups of patients with schizophrenia as well as healthy controls (n = 26). Patients (n = 27) in the first group, had no family history of schizophrenia and had experienced severe pregnancy and birth complications (PBCs). The second group comprised of patients (n = 21) without a history of severe PBCs from families multiply affected with schizophrenia. RESULTS: Reduction of the left hippocampal volume was associated with the diagnosis of schizophrenia but was present only in patients with a history of severe PBCs; in this group the smaller hippocampal volume, the earlier the onset of psychosis. CONCLUSIONS: Our findings suggest that environmental factors, in this case severe PBCs, make a significant contribution to hippocampal abnormalities in schizophrenia.

Adult↗
PubMed1999

A comparison of the utility of dimensional and categorical representations of psychosis. UK700 Group.

BACKGROUND: The usefulness of any diagnostic scheme is directly related to its ability to provide clinically useful information on need for care. In this study, the clinical usefulness of dimensional and categorical representations of psychotic psychopathology were compared. METHOD: A total of 706 patients aged 16-65 years with chronic psychosis were recruited. Psychopathology was measured with the Comprehensive Psychopathological Rating Scale (CPRS). Lifetime RDC, DSM-III-R, and ICD-10 diagnoses and ratings of lifetime psychopathology were made using OPCRIT. Other clinical measures included: (i) need for care; (ii) quality of life; (iii) social disability; (iv) satisfaction with services; (v) abnormal movements; (vi) brief neuropsychological screen; and (vii) over the last 2 years--illness course, symptom severity, employment, medication use, self-harm, time in hospital and living independently. RESULTS: Principal component factor analysis of the 65 CPRS items on cross-sectional psychopathology yielded four dimensions of positive, negative, depressive and manic symptoms. Regression models comparing the relative contributions of dimensional and categorical representations of psychopathology with clinical measures consistently indicated strong and significant effects of psychopathological dimensions over and above any effect of their categorical counterparts, whereas the reverse did not hold. The effect of psychopathological dimensions was mostly cumulative: high ratings on more than one dimension increased the contribution to the clinical measures in a dose-response fashion. Similar results were obtained with psychopathological dimensions derived from lifetime psychopathology ratings using the OCCPI. CONCLUSIONS: A dimensional approach towards classification of psychotic illness offers important clinical advantages.

Adolescent↗