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Biomedical subjects

H Kaiya

Publications and source records attributed to H Kaiya.

At least 19 recordsLinked to original sources

Second messenger imbalance hypothesis of schizophrenia.

Based on the results of studies on intracellular signaling in platelets of schizophrenics, an imbalance of the second messenger system is proposed: Diacylglycerol (DG), which activates protein kinase C (PKC), was increased, while adenylate cyclase (AC)-cAMP function was decreased. It is proposed that the increased DG/PKC function may entail a decrease in inositol 1,4,5-trisphosphate (IP3)/Ca2+ function and lowering of phosphoinositide turnover. If such a pathological intracellular signaling takes place in the brain, it may cause a distorted balance of protein activation via phosphorylation in neurons, resulting in some of the deficits of schizophrenia. Neuroleptics have been reported to antagonize the above-mentioned pathological processes of intracellular signaling. The imbalance hypothesis of the DG/PKC pathway and AC-cAMP pathway is not inconsistent with the dopamine hypothesis of schizophrenia, because dopamine receptor stimulation is indirectly related to reduction in IP3/Ca2+ function and lowering of phosphoinositide metabolism.

Antipsychotic Agents

Essential and other fatty acids in plasma in schizophrenics and normal individuals from Japan.

Plasma phospholipid and cholesterol ester fatty acid levels were measured in samples from normal individuals, schizophrenics, and patients with affective and paranoid disorders in Japan. The schizophrenics were divided into groups with normal and reduced platelet sensitivity to the aggregation-inhibiting effects of prostaglandin (PG) E1. As in samples from schizophrenics in several other countries, linoleic acid levels were significantly below normal, as was the ratio of linoleic acid to its metabolites. Phospholipid fatty acid levels were normal in patients with paranoid or affective disorders. When the schizophrenics were divided into those with and without an abnormal response to PGE1, oleic acid was higher and eicosapentaenoic acid lower in those patients with an abnormal response. This study lends further support to the idea that schizophrenics may differ from controls in their essential fatty acid and eicosanoid metabolism.

Adult

Distinct cellular expression of pertussis toxin-sensitive GTP-binding proteins in rat cerebellum.

Immunohistochemical localization of pertussis toxin-sensitive GTP-binding proteins in rat cerebellum was investigated using antibodies raised against purified G alpha o and synthetic peptides corresponding to specific sequences of G alpha i1, G alpha i2 and G alpha o was detected mostly in the molecular layer but not in the cell body of the Purkinje cells. G alpha i1 and G alpha i2 were found predominantly in the molecular layer and in addition in the cell body of the Purkinje cells. G alpha i3 was not detected in rat cerebellum. Immunoblot analysis demonstrated that in the cerebellum membrane G alpha 0 was most abundant and surprisingly the amount of G alpha i2 was much higher than that of G alpha i1. Thus, each pertussis toxin substrate was found to be expressed differently in rat cerebellum. The different patterns of expression imply that each subtype of GTP-binding proteins may have a specific function in modulating the neuronal activity in rat cerebellum.

Amino Acid Sequence

Electroconvulsive treatment: effects on phospholipase C activity and GTP binding activity in rat brain.

The effect of electroconvulsive treatment (ECT) on activities of phospholipase C hydrolyzing phosphatidylinositol (PI-PLC) and phosphatidylinositol 4,5-bisphosphate (PIP2-PLC) and guanosine-5'-(3-O-thio)triphosphate (GTP gamma S) binding activity were examined in membrane and cytosol fractions from four discrete areas (prefrontal cortex, hippocampus, striatum, and amygdala) of the rat brain. A single ECT resulted in an increase in cytosolic activities of PI-PLC in the prefrontal cortex and of PIP2PLC in all 4 brain regions examined. There were no significant changes in either PI-PLC or PIP2-PLC activity in membrane fractions after a single ECT. Repeated ECT caused regionally specific changes in PLC activities as follows: in the prefrontal cortex, both cytosolic PI-PLC and PIP2-PLC and membranous PI-PLC activities were decreased; in the hippocampus, no changes in any PLC activities were seen; in the striatum, only membranous PI-PLC activities were increased; and, in the amygdala, cytosolic and membranous PI-PLC and cytosolic PIP2-PLC activities were increased. The pattern of changes in GTP gamma S binding activity following repeated ECT resembled those found in PLC activity as follows: in the prefrontal cortex, GTP gamma S binding activities were significantly reduced in both membrane and cytosol; in the hippocampus, the activity was decreased in membrane; in the striatum, no changes in GTP gamma S binding activity were seen in any fraction; and, in the amygdala, the activity was increased in cytosol. These findings suggest that ECT has complex effects on the G protein-phospholipase C system, possibly affecting neuronal signal transduction.

Animals

Transient global amnesia and Raynaud's phenomenon in scleroderma.

Transient global amnesia (TGA) is a well-recognized clinical entity, but its pathophysiology and prognosis have remained arguable. We reported that a 63-year-old woman with scleroderma developed two TGA episodes. The patient sometimes suffered from headaches when Raynaud's phenomenon appeared in her fingers, but she did not experience further cerebrovascular events. This case suggests that the unique clinical presentation of this syndrome may result from an ischemic event, possibly triggered by a vasospastic mechanism like Raynaud's phenomenon.

Amnesia

Coping styles to basic disorders among schizophrenics.

Coping efforts to subjectively experienced basic disorders were investigated by self-report in 60 chronic schizophrenics in Japan, and the relationships to clinical and demographic variables, intelligence, personality, and attitude toward their illness were analyzed. Self-reports on coping efforts were obtained for more than half of all subjectively experienced basic disorders, and the predominant technique was reported to be the approach oriented towards problem-solving. Within each coping style, the behavioral change, divertive problem-solving approach correlated negatively with hospitalization and symptoms, and the struggle, problem-solving efforts without any effective results correlated positively with symptoms. Suggestions regarding integration of these self-efforts into psychosocial treatment of schizophrenia are discussed.

Adaptation, Psychological

Platelet prostaglandin E1 hyposensitivity in schizophrenia: decrease in cyclic AMP formation and in inhibitory effects on aggregation.

Cyclic adenosine monophosphate (cAMP) formation via prostaglandin E1 (PGE1) or forskolin stimulation was determined in washed platelets from 35 schizophrenic patients and 34 normal controls. The inhibitory effects of PGE1 and forskolin on platelet aggregation response (PAR) elicited by adenosine diphosphate (ADP) were also examined simultaneously. Both PGE1- and forskolin-stimulated cAMP formation decreased in platelets from schizophrenic patients, as compared with those from normal controls. PGE1 inhibition of PAR was significantly lowered in schizophrenic patients compared to normal controls, but forskolin inhibition was not. No correlations between PGE1- or forskolin-stimulated cAMP formation and inhibitory effects of PGE1 or forskolin on PAR, respectively, were explained by the complex factors involved in PAR. In conclusion, platelet hyposensitivity to PGE1 in schizophrenic patients is partially based on aberrant adenylate cyclase (AC) activity and includes other variables related to PAR.

Adult

Elevated plasma prostaglandin E2 levels in schizophrenia.

Plasma levels of prostaglandin E2 (PGE2) were determined with radioimmunoassay in 40 DSM-III schizophrenics, 15 patients with other mental disorders, and 23 normal controls. The mean value of plasma immunoreactivity of PGE2 was significantly higher in the schizophrenic patients than in the normal controls. Schizophrenic patients with high plasma PGE2 levels had more guilt feelings and hallucinatory behavior on BPRS, relatively successful heterosexual relations, and a higher incidence of birth complications.

Adolescent

Accumulation of diacylgylcerol in platelet phosphoinositide turnover in schizophrenia: a biological marker of good prognosis?

Phosphoinositide (PI) turnover was examined by measuring phosphatidic acid (PA) and diacylglycerol (DG) production following thrombin stimulation in platelet membranes from 20 schizophrenic patients, 10 patients with other mental disorders, and 9 normal controls. In 6 of 13 acute schizophrenic patients, DG was not transformed into phosphatidic acid (PA), but accumulated in the platelets instead. The abnormal findings persisted for at least 2 months, but then reversed over a long period. Three years later, the patients with abnormal PI turnover had a significantly better outcome than other acute schizophrenic patients.

Adolescent

Platelet prostaglandin E1 hyposensitivity in schizophrenia: reduction of prostaglandin E1- or forskolin-stimulated cyclic AMP response in platelets.

Cyclic 3',5'-adenosine monophosphate (cAMP) formation via prostaglandin E1 (PGE1)-or forskolin-stimulation were determined in washed intact platelets from 32 schizophrenic patients and 30 normal controls. Regarding basal cAMP levels in the platelets, there were no differences between schizophrenic patients and normal controls. Both PGE1-and forskolin-stimulated cAMP response reduced in platelets from schizophrenics compared with normal controls. These results suggested that platelets in schizophrenics were impaired not only in the adenylate cyclase unit per se but also extensively in the cAMP generating system coupled to a PGE1 receptor.

Adenylyl Cyclases

Midsagittal cortical pathomorphology of schizophrenia: a magnetic resonance imaging study.

Forty schizophrenic patients and 17 normal controls underwent magnetic resonance imaging (MRI) of the brain. All subjects were consenting males under 50 years old. Enlargement of the septum pellucidum in schizophrenics was confirmed. This finding was significantly related to a family history of the disorder. Although this study could not confirm a decreased frontal:brain ratio (FBR) in schizophrenics as reported by Andreasen et al. (1986), a negative correlation between FBR and negative symptoms was seen. No significant differences in other cerebral substructures, cerebellar vermis, or fourth ventricle of the midsaggital cut were seen between schizophrenics and normal controls. However, it is of interest that a small cerebellar vermis:brain ratio was associated with good therapeutic response to neuroleptics in schizophrenics. All these findings suggest that combining morphological changes in the brain as illustrated by MRI with clinical variables may provide a useful new approach to the subclassification of schizophrenia.

Adult

Computerised tomography in schizophrenia. Familial versus non-familial forms of illness.

Findings on CT and demographical or clinical data in 80 patients with DSM-III schizophrenia and 45 medical controls were evaluated. Multiple-discriminant analysis showed that the enlargement of the third ventricle and frontal and parietal atrophy could significantly predict the diagnosis of schizophrenia. Widening of Sylvian fissures and parietal atrophy differentiated familial schizophrenics of both horizontal transmission (who had affected siblings) and vertical transmission (who had affected parents or/and offspring) from non-familial patients. Parietal atrophy and a history of birth complications differentiated horizontal from vertical transmission. The CT findings together with some clinical characteristics could differentiate the three subgroups classified by the hereditary form; thus each of these subgroup may belong to a different disease entity, of a different pathophysiology.

Adult

Regional distribution of phosphoinositide-specific phospholipase C activity in rat brain.

The phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolytic activities of phosphoinositide-specific phospholipase C (PLC) were measured in membrane and cytosol fractions from 7 discrete areas of the rat brain. Both the PI-PLC and PIP2-PLC specific activities were found to differ significantly among the 7 discrete brain areas. In the membrane fraction, the PIP2-PLC activity was higher than that of PI-PLC in each region, suggesting that the PLC in membranes prefers PIP2 to PI as substrate. The PIP2-PLC activities in the membrane were high in prefrontal cortex and cerebellum, but rather low in medulla oblongata and hypothalamus. The PI-PLC specific activity in the cytosol was significantly higher than that in the membrane of all brain areas examined. The PI-PLC specific activity in membranes is inversely proportional to its activity in the cytosol. In the cytosol fraction, the distribution pattern of PI-PLC specific activity resembled that of PIP2-PLC. These results indicate that PLCs are differently distributed in various regions of rat brain, and suggest the regional differences in neuronal transduction.

Animals