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N Takei

Publications and source records attributed to N Takei.

At least 91 records · Page 5Linked to original sources

Involvement of phosphatidylinositol-3 kinase in prevention of low K(+)-induced apoptosis of cerebellar granule neurons.

Cerebellar granule neurons obtained from 9-day-old rats die in an apoptotic manner when cultured in serum-free medium containing a low concentration of potassium (5 mM). A high concentration of potassium (26 mM) in the culture medium and BDNF can effectively prevent this apoptosis. The survival effects of high potassium and BDNF were additive, and the effect of high potassium was not blocked by addition of anti-BDNF antibody. These observations indicated that these survival effects were independent. To examine which molecules are involved in the survival pathway induced by BDNF or high K+, we used wortmannin, a specific inhibitor of PI-3 kinase. Wortmannin blocked the survival effects of both BDNF and high K+ on cerebellar granule neurons. Furthermore, in vitro PI-3 kinase assay showed that treatment with BDNF or high K+ induced PI-3 kinase activity, which was diminished by addition of wortmannin. These results indicate that different survival-promoting agents, BDNF and high K+, can prevent apoptosis in cerebellar granule neurons via a common enzyme, PI-3 kinase.

Androstadienes↗

NGF and BDNF increase the immunoreactivity of vesicular acetylcholine transporter in cultured neurons from the embryonic rat septum.

The expression of vesicular acetylcholine transporter (VAChT), which transports ACh into synaptic vesicles, is coregulated with choline acetyltransferase (ChAT). Therefore, the effects of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) on the levels of VAChT in cultured neurons from the septum of embryonic rats were investigated by immunocytochemistry. NGF and BDNF increased the number of VAChT-immunoreactive neurons by approximately 1.5-fold and enhanced the immunoreactivity in each positive cell. These results suggest that the neurotrophins enhance not only synthesis but also storage of ACh in septal neurons.

Acetylcholine↗

Seasonality of birth in schizophrenia: the effect of regional population density.

It has been suggested that winter birth in urban areas may be associated with an increased risk of schizophrenia. Data on 4139 patients with a hospital diagnosis of schizophrenia were obtained from a survey of public departments of psychiatry in metropolitan France. Place of birth was classified according to the administrative subdivision of French territory into 95 'départements'. Density of population in the decade and in the département of birth was identified using successive census data. A 20% excess (OR, 1.20; 95% CI, 1.03-1.40; p = 0.02) of winter births (January-March) was found among patients born in highly densely populated areas (> 136 inhabitants/km2) compared to those born in other areas. These results suggest that seasonal early environmental risk factor(s) linked to schizophrenia predominantly operate in urban areas.

Adolescent↗

The Maudsley Family Study, II: Endogenous event-related potentials in familial schizophrenia.

Auditory event-related potentials (ERPs) were obtained from 33 schizophrenics, from 16 families multiply affected with schizophrenia, 57 of their non-schizophrenic first-degree relatives and 32 unrelated healthy controls. Transmission of schizophrenia in these families appeared unilinear with one parent only transmitting the disorder. Consequently, we were able to identify 10 presumed obligate carriers and study eight of them. Schizophrenic patients showed latency prolongation and amplitude reduction of the N100, N200 and P300 waves compared to controls. Their relatives showed similar abnormalities compared to controls. There was a trend for bimodal distribution of the P300 latency in the relatives, with 20 (35%) of them falling outside two standard deviations of the mean of the controls. These included six of the eight obligate carriers. Our results suggest that ERP abnormalities may serve as markers of genetic vulnerability in schizophrenia and may be useful in genetic linkage studies.

Adult↗

Low serum cholesterol in suicide attempters.

Previous studies have shown an association between low serum cholesterol concentration and suicide; however, conflicting results have also been reported. To examine this potential association, cholesterol levels in 99 patients admitted to an emergency ward following an attempted suicide were compared with those in 74 nonsuicidal psychiatric inpatients, and those in 39 psychiatrically normal individuals with accidental injuries. Cholesterol concentrations in suicide attempters were found to be significantly lower compared with both psychiatric and normal controls, when sex, age, psychiatric diagnosis, and physical conditions (serum total protein and red blood cell count) were adjusted for. This significant relationship was observed in mood disorders and personality or neurotic disorders, but not in schizophrenia spectrum disorders. These results support the previous claim that lower cholesterol level is associated with an increased risk of suicidal behavior.

Adult↗

Identification of NAP-22 and GAP-43 (neuromodulin) as major protein components in a Triton insoluble low density fraction of rat brain.

NAP-22 is a membrane-localized brain enriched acidic protein having a Ca(2+)-dependent calmodulin binding activity. Further fractionation of the NAP-22 containing membrane showed the localization of NAP-22 in a Triton insoluble fraction of low density. Besides NAP-22, this fraction was found to contain GAP-43 (neuromodulin), trimeric G proteins, and some GPI-anchored proteins such as Thy-1 and N-CAM-120. Presence of some protein tyrosine kinases, such as src and fyn, was also shown.

Amino Acid Sequence↗

Brain-derived neurotrophic factor increases the stimulation-evoked release of glutamate and the levels of exocytosis-associated proteins in cultured cortical neurons from embryonic rats.

Differentiation and survival of neurons induced by neurotrophins have been widely investigated, but little has been reported about the long-term effect of brain-derived neurotrophic factor (BDNF) on synaptic transmission. Among many steps of neurotransmission, one important step is regulated release of transmitters. Therefore, the release of glutamate and GABA from cortical neurons cultured for several days with or without BDNF was measured by an HPLC-fluorescence method. Although BDNF had little effect on the basal release of glutamate, high K(+)-evoked release was greatly increased by BDNF. BDNF also tended to increase evoked release of GABA. Recently, several proteins involved in the step of "regulated release" have been identified. Thus, the effect of BDNF on the levels of these proteins was then investigated. Neurons were cultivated with or without BDNF, collected, and electrophoresed for western blotting. BDNF increased levels of synaptotagmin, synaptobrevin, synaptophysin, and rab3A, which were known as vesicle protein. Levels of syntaxin, SNAP-25, and beta-SNAP were also increased by BDNF. In addition, the numbers of cored and clear vesicles in nerve terminals or varicosities were also increased by BDNF. These results raise the possibility that BDNF increases regulated release of neurotransmitters through the up-regulation of secretory mechanisms.

Animals↗

Evaluation of heterotopic bone formation induced by squalane and bone morphogenetic protein composite.

Bone morphogenetic protein is an important molecule whose bioactivity depends on the carrier. Squalane is used in the formulation of various kinds of cosmetics because it is easily emulsified and has the property of spreading well. Thus, squalane might be effective as a bone morphogenetic protein delivery system. As a test for this possibility, gelatin capsules containing squalane and bone morphogenetic protein (bovine derived partially purified) composite were implanted under the hind-quarter perimuscular membrane of ddY mice. Control capsules containing only bone morphogenetic protein were used for controls. The implants were radiographically and histologically examined at 1 to 4 weeks after the operation. According to the radiographic analysis, squalane and bone morphogenetic protein composite and bone morphogenetic protein only control specimens formed widespread heterotopic bone tissues. The amount of heterotopic bone formation in the composite experimental specimens was approximately 40% greater than that in the controls. Histologic examination of experimental and control specimens revealed varying amounts of perichondral ossification by 2 weeks. By 3 and 4 weeks, the bone deposits were colonized by hematopoietic bone marrow. Squalane was effective for the slow local release of bone morphogenetic protein. Furthermore, the squalane and bone morphogenetic protein composite was a reliable osteoinductive biomaterial.

Animals↗

Obstetric complications and age at onset in schizophrenia: an international collaborative meta-analysis of individual patient data.

OBJECTIVE: An excess of obstetric complications in the histories of schizophrenic patients is a well-replicated finding, but less consistent results have been found concerning the relationships between obstetric complications and family history of schizophrenia, age at onset of schizophrenia, and gender. Small sample size limited the power of previous studies that attempted to assess such relationships. The aim of this study was to use data on individual patients from all available studies to examine the links between a history of obstetric complications and family history of schizophrenia, age at onset, and gender. METHOD: Raw data from 854 schizophrenic patients concerning history of obstetric complications rated according to the Lewis and Murray scale were obtained from 11 different research groups. Weighted average estimates were calculated with the use of regression techniques. RESULTS: A significant association was found between age at onset of schizophrenia and obstetric complications: the earlier the age at onset, the more likely the history of obstetric complications. Subjects with onset of schizophrenia before age 22 were 2.7 times more likely than those with onset at a later age to have had a history of abnormal presentation at birth and 10 times more likely to have had a history of complicated Cesarean birth. No association was found between obstetric complications and family history of schizophrenia or gender. CONCLUSIONS: The association between obstetric complications and early age at onset of schizophrenia indicates that the pathophysiology of early-onset schizophrenia involves neurodevelopmental impairment.

Adolescent↗

Increased rate of psychosis among African-Caribbeans in Britain is not due to an excess of pregnancy and birth complications.

BACKGROUND: It has been suggested that the increased rate of psychotic illness among African-Caribbeans living in Britain is due to an excess of pregnancy and birth complications (PBCs). METHOD: We therefore compared the frequency of PBCs in a group of White psychotic patients (n = 103) and a comparable group of patients of African-Caribbean origin (n = 61); the latter consisted of 30 first-generation (born in the Caribbean) and 31 second-generation (born in Britain) individuals. RESULTS: White psychotic patients were more than twice as likely to have a history of PBCs as their African-Caribbean counterparts (odds ratio = 2.34, 95% confidence interval (CI) 0.88-6.47, P = 0.062). The same trend was observed among patients with a DSM-III diagnosis of schizophrenia (odds ratio = 1.65, 95% CI 0.56-4.97, P = 0.32). The rate of PBCs was similar among the first- and second-generation Caribbean psychotic patients. CONCLUSIONS: The increased rate of psychotic illness that has been reported among the African-Caribbean population in Britain is not due to an increased prevalence of PBCs.

Adult↗

Relationship between in utero exposure to influenza epidemics and risk of schizophrenia in Denmark.

Several recent epidemiological studies suggest that exposure to influenza during gestation increases the risk of later developing schizophrenia. Inconsistency exists, however, particularly in studies that have examined the relationship between the prevalence of influenza and the monthly number of schizophrenic births, over many years. Our sample (N = 9462) was obtained from a Danish computerized case register, and consisted of schizophrenia patients born between 1915 and 1970, and first admitted to Danish psychiatric hospitals between 1971 and 1991. The study sample was chosen to represent "incidence cases" to allow us to calculate the population attributable risk fraction (PAF). The temporal correlation of fluctuations in the prevalence of influenza and fluctuations in the monthly number of preschizophrenic births was examined using a Poisson regression analysis. Exposure to influenza 4 months prior to birth (i.e., about the 6th month of gestation) was significantly associated with an increased risk of later schizophrenia, especially for narrowly defined schizophrenia. The number of schizophrenic births was found to have risen by 12% (95% confidence interval: 1-24%) for every 100,000 cases of influenza in the 4th month before birth. Our model indicates the PAF to be 1.4%, that is, only 1.4% of the whole schizophrenic sample is attributed to prenatal exposure to influenza. Although maternal exposure to influenza during midgestation is not a major risk factor for schizophrenia, the elucidation of its causal mechanism may open the avenue to understanding the neurodevelopmental origins of the disease.

Adult↗

A role of peroxides in Ca2+ ionophore-induced apoptosis in cultured rat cortical neurons.

The implication of reactive oxygen species for the Ca2+ ionophore ionomycin-induced apoptosis was investigated in cultured cortical neurons from embryonic rats. Ionomycin increased the production of intracellular peroxides as measured by flow cytometric analysis with 6-carboxy-2'7'-dichorodihydrofluorescein diacetate, di(acetoxymethyl ester). Low doses of ionomycin increased the level of manganese-superoxide dismutase (Mn-SOD). In addition, N-acetyl-L-cysteine prevented apoptotic neuronal death induced by ionomycin in a dose-dependent manner. Buthionine sulfoximine suppressed the effect of N-acetyl-L-cysteine. These results suggest that peroxides and redox-regulation play an important role in the apoptosis of neurons induced by elevation of intracellular Ca2+ concentration.

Acetylcysteine↗

A survey of prescribing practice of antipsychotic maintenance treatment for manic-depressive outpatients.

Survey questionnaires were mailed to public hospital psychiatrists practising in a French region to obtain information on the manic-depressive outpatients they personally followed up. Data were collected on 222 manic-depressive outpatients managed by 43 separate psychiatrists. More than two thirds were receiving at least one antipsychotic, and 17% were prescribed a depot-neuroleptic. Predictors of antipsychotic prescription were a history of psychotic features (OR = 3.4; 95%CI 1.7-6.9), early age at onset (OR = 2.1; 95%CI 1.0-4.8) and low educational level (OR = 3.1; 95%CI 1.5-6.3). Similar predictors were found for depot-neuroleptic prescription. Although these indicate that the prescription of antipsychotic for manic-depressive outpatients is not random, only 14% of patients were receiving mood stabilizers only. Owing to the potential side effects of antipsychotics, the benefit-to-risk ratio of antipsychotic use in the maintenance treatment of manic-depressive patients has to be carefully taken into account.

Adolescent↗

Season of birth and eating disorders.

A statistically significant season of birth variation is found in an unselected nationwide sample of 1,939 eating disorders patients, with peak season of birth occurring in May. However, among younger patients (n = 882), peak season of birth is in March, which is statistically significantly different to that expected from the general population season of birth cycle. This finding may imply links between etiology of earlier-onset eating disorders and the psychoses; similar first quarter peak seasonal patterns of birth have been found in schizophrenic and affective psychoses--with birth peaks in January and February. In contrast, for the neuroses and personality disorders, birth peaks have been found to be in June and August, similar to the June birth peak found in this study for later-onset eating disorders (n = 1,057), which was not statistically significantly different to season of birth peaks expected from general population data.

Adult↗

The incidence of mania: time trends in relation to gender and ethnicity.

In order to investigate conflicting reports about possible changes in the incidence of mania, we established first contact rates for mania in the defined area of Camberwell between 1965 and 1984. There was some evidence for an increase in the first contact rate of mania, especially in females. This rise may be associated with the influx into Camberwell of individuals of Afro-Caribbean origin who showed significantly higher rates than the white group [adjusted rate ratio 3.1; 95% confidence interval (CI) 1.4-6.9] and more often displayed mixed manic and schizophrenic symptomatology (risk ratio 2.2; 95% CI 1.1-4.3). We conclude that the incidence of mania has not decreased and may actually have increased. High rates of mental illness among members of ethnic minorities are not specific to schizophrenia, suggesting that a risk factor common to both manic and schizophrenic illness is more prevalent among these groups.

Adolescent↗