Morphological alteration in hippocampus after status epilepticus induced by intra-amygdaloid injection of dibutyryl-cAMP in rats.
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Biomedical subjects
Publications and source records attributed to H Kumashiro.
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The function of the hypothalamic-pituitary-adrenal axis (HPA-axis) and its association with clinical features in chronic schizophrenia were investigated. Twenty of 33 chronic schizophrenics exhibited an abnormal diurnal variation of the saliva cortisol level. The patients with abnormal diurnal variation gave higher scores for some negative symptoms than those with normal diurnal variation. On the dexamethasone suppression test (DST) of saliva samples, 13 of 34 chronic schizophrenics were abnormal. The patients with DST nonsuppression were more frequently classified into disorganized type and exhibited low scores of anxiety compared with the patients with normal suppression. The 9 patients who showed abnormal diurnal variation and DST nonsuppression were more frequently classified into disorganized type and showed higher scores of negative symptoms than the 9 patients who did not show any abnormal cortisol data. These results suggest that there might be some disturbance in the function of the HPA-axis in a group of chronic schizophrenics and that these patients might have severe negative symptoms.
To examine the noradrenergic function in endogenous depression, binding of a selective agonist radioligand, 3H-UK14304, to platelet alpha 2-adrenergic receptors and plasma free 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured in untreated depressed patients. The effects of an antidepressant, mianserin, on these parameters were also assessed. The Bmax and Kd values for 3H-UK14304 binding in 26 untreated depressed patients were significantly higher (p less than 0.05, p less than 0.01) than those in 26 normal controls. On the other hand, there were no significant differences in plasma free MHPG levels between 12 untreated depressed patients and 12 normal controls. Chronic administration of mianserin to 8 depressed patients slightly increased the Bmax and Kd values. However, plasma free MHPG levels did not change after treatment. These findings suggest that depression is related to the subsensitivity of alpha 2-receptors as indicated by a decreased affinity of platelet alpha 2-receptors. In addition, chronic administration of mianserin further decreased the affinity of alpha 2-receptors. This suggests that mianserin acts not only on alpha 2-receptors but also on the other neurotransmitter systems.
Plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) was measured in 19 patients with acute schizophrenia before and after neuroleptic therapy. Plasma antinoradrenergic activity (pANA) of the neuroleptics used was measured after treatment. Before treatment, pMHPG was higher in the patients than in 20 normal controls. There was a positive correlation between pMHPG level and the global severity of positive symptoms. After neuroleptic therapy, pMHPG was reduced, and there was a significant correlation between the decline in pMHPG and the improvement in positive symptom score. The decline in pMHPG was also correlated with pANA. These results suggest that there is a dysfunction of the noradrenergic system in the brains of some acute schizophrenics with mainly positive symptoms, and that this dysfunction may be improved, along with positive symptom score, after neuroleptic therapy.
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A-39-year-old man was admitted to our hospital because of a markedly decreased level of serum cholinesterase found incidentally by a blood test. Detailed examination did not reveal severe liver disease, malignant tumor, infection or organophosphate compound poisoning. Investigation of three generations of his family revealed two homozygous and five heterozygous family members with the cholinesterase deficiency gene E1s indicating familial serum cholinesterase deficiency.
The possible role played by superoxide dismutase (SOD), a major defense system for counteracting the toxic effects of oxygen free radicals, in amygdaloid (AM) kindling was examined in rats. A significant increase of total SOD activity in the whole brain was observed 30 days after completion of AM kindling. Intra-AM injection of 3 ng of one of the 2 SOD enzymes present in mammalian brain, i.e. cytosolic SOD containing copper and zinc (CuZn-SOD) caused suppression of kindled seizure. These results suggest that SOD participates in the persistence of AM kindled seizure susceptibility and the initiation of kindled AM seizure.
Eye movements in response to visual stimuli (Benton Visual Retention Test) were examined in 22 temporal lobe epileptics (TLEs), 10 primary generalized epileptics (PGEs), and 20 normal controls. In the normal controls, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, a tendency also found in the PGEs. In TLEs with right-sided foci, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, the direction of asymmetry found in the normal controls and PGEs. However, when calculated as laterality indices (the degree of asymmetry) TLEs with right-sided foci were significantly more negative than those of both the normal controls and PGEs. In TLEs with left sided foci, the percent fixation time on the right peripheral figure tended to be higher than that on the left peripheral figure, an asymmetry which differed significantly from the normal controls, PGEs and the TLEs with right-sided foci. The results here showed that TLEs with unilateral foci had distinct eye movements which varied with the laterality of the lesion in the direction of functional overactivation of the epileptogenic hemisphere.
gamma-D-glutamylaminomethylsulphonic acid (GAMS), a preferential antagonist of non-NMDA receptors (kainate and quisqualate receptors), was injected into the kindled amygdala (AM) of rats. When the kindled AM was stimulated at the previously established generalized seizure triggering threshold (GST) one hour after the GAMS (1 or 2 mumol) injection, afterdischarge (AD) generation was completely suppressed. However, a re-stimulation at the intensity of 40-200 microA above the GST generated AD associated with Stage 1 or 5 seizure. Our result suggests an important role played by non-NMDA receptors in the expression and generalization of AM-onset seizures.
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To assess the relative contribution of antiepileptic drugs (AEDs) toward the occurrence of congenital malformation, two prospective studies (previous and present) were compared. In the present subjects of 145 cases, the total daily dose of AEDs (drug score) in each case was decreased as much as possible, and polypharmacy was changed to monopharmacy before conception where it was possible. The incidence of malformations significantly decreased from 13.5% to 6.2% (p = 0.031) by the change in drug regimen. The drug score, number of AEDs, maternal age at delivery, seizure type, and etiology of epilepsy were statistically different between the two study groups. Even after the correction of the data by the last three factors, the difference in the incidence of malformation did not disappear, while it disappeared if data were corrected either by the drug score or number of AEDs. These results suggest that the possibility of prevention of AED related malformations is possible by an improvement in AED therapy.
Liposomes (LIPO), which are concentric lipid layers alternating with aqueous compartments, have been suggested as a potential carrier for various drugs. In the previous studies, we have demonstrated that anticonvulsant drugs such as valproic acid, phenytoin, and DN-1417 (an analog of thyrotropin-releasing hormone) entrapped into LIPO exert more prominent therapeutic efficacy than parent drugs. In the present study, we examined the comparative effects of Lidocaine (LDCA) which acts as a proconvulsant as well as an anticonvulsant, and LIPO-entrapped LDCA (LDCA-L) on limbic status epilepticus originating in the amygdala (AM) of rats. LDCA (LDCA hydrochloride) was dissolved in distilled water as a vehicle at a concentration of 2.5 mg/ml or 10 mg/ml. LIPO and LDCA-L were prepared from L-alpha-phosphatidylcholine, cholesterol, and stearylamine. Status epilepticus was induced by intra-AM injection of combined dibutyryl (db)-cAMP-200 micrograms/ethylene diaminetetraacetic acid (EDTA)-67.2 micrograms through the implanted cannula. The animals were divided into 4 groups which received vehicle (n = 6), LIPO (n = 5), LDCA (n = 9), and LDCA-L (n = 10). LDCA group was subdivided into 5 mg/kg (n = 4) and 20 mg/kg (n = 5) groups. LDCA-L group was treated with 5mg/kg (n = 4) or 20mg/kg (n = 6). All drugs were intravenously given at a volume of 2ml/kg via teflon tube previously inserted into cervical vein 30 min after db-cAMP/EDTA injection. Vehicle or LIPO alone did not alter the pattern of electroclinical ictal responses produced by intra-AM injection of db-cAMP/EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)
The present paper reports 3 cases of aphasia with small lesions in the region of the basal ganglia to discuss whether neostrial dysfunction can cause aphasic symptoms. The Standard Language Tests of Aphasia (SLTA) was used to assess the type and degree of aphasia. Two patients with infarction either in the left putamen or in the head of the left caudate nucleus showed severe disturbance only in recalling words, especially nouns. The other patient showed the same symptom, in addition to writing disturbance that developed shortly after surgical extirpation of an arteriovenous malformation (AVM) in the left caudate nuclei. The symptoms common to the 3 patients corresponded well to the "anomic aphasia" proposed by Benson. The aphasic symptoms disappeared completely or largely within several months. This easy reversibility suggests that the aphasic disorder in the three patients was caused by damage not to the basal ganglia themselves, but to the affecting axons passing through or by the nuclei.
Recent studies have demonstrated that intramuscular administration of thyrotropin-releasing hormone (TRH) or its analogue improves various clinical aspects of intractable epilepsy such as Lennox-Gastaut syndrome, West syndrome, and myoclonus epilepsy. Other clinical studies reported efficient property of intravenous TRH against status epilepticus. However, it is also true that intravenous TRH produces epileptic seizures in patients with epilepsy or organic brain damage. Thus, the utility of intravenous TRH for the treatment of status epilepticus seems to be equivocal. To further explore the problem in this regard, we examined the effect of TRH on limbic status epilepticus in rats. Thirty-eight male Wistar rats weighing 180-220g were used. Status epilepticus was induced by intracerebral injection of a combination of 200 micrograms of dibutyryl-cAMP (db-cAMP) and 67.2ng of ethylenediaminetetraacetic acid (EDTA) into the amygdala (AM) through an implanted cannula. 30 min later, TRH or vehicle (distilled water) was administered intravenously (i.v.) or intracerebroventricularly (i.c.v.). Although 3 mg/kg of TRH (n = 9), when injected i.v., did not alter the pattern of electroclinical ictal responses induced by db-cAMP/EDTA, 25 mg/kg (n = 5) and 50 mg/kg (n = 5) of TRH significantly exaggerated EEG and/or behavioral ictal seizures, beginning immediately after the injection and lasting for more than 30 min. With 50 mg/kg of TRH, the exaggerated seizure patterns were followed by marked suppression of electroclinical seizures. 50 micrograms of i.c.v. TRH (n = 5), like higher doses of i.v. TRH, caused a slight, but not a significant, build up of electroclinical ictal seizures, beginning immediately after the injection and lasting for about 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Kindling was induced in rats by electrical stimulation of the lateral portion of the substantia innominata (SI). The pattern of seizure development was similar to that of amygdala (AM) kindling. However, lateral SI kindling was associated with ipsilateral head turning as an initial manifestation. In addition, lateral SI kindling had a higher afterdischarge threshold than AM kindling, and the generalized seizure triggering threshold was more unstable in SI kindling than in AM kindling. These findings suggest that lateral SI participates in, but is not essential for, AM seizure development in rats.
The gene of catalytic domain of the protein kinase of RSV-scr was cloned into the BamHI cloning site of translation vector pET-8c which containing T7 RNA polymerase promotor, and transformed BL21 (DE3) pLys S (Studier and Moffatt, 1986). The putative molecular weight of the protein was about 33 kd as evaluated on the basis of its nucleotide size showed the identical mobility in SDS-polyacrylamide gel electrophoresis. However, yield of protein production was not high, probably, because of its instability in Escherichia coli.
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