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Biomedical subjects

K Kashihara

Publications and source records attributed to K Kashihara.

At least 55 records · Page 3Linked to original sources
PubMed1997

AMPA receptors modulate dopamine release in the striatum, as measured by brain microdialysis.

The effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f) quinoxaline (NBQX), a potent and selective antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, on the release of dopamine from the striatum was investigated in freely moving rats using an in vivo microdialysis technique. Perfusion with 1.0 mM AMPA increased the concentration of striatal extracellular dopamine. After systemic administration of NBQX (40 mg/kg, i.p.), dopamine levels in the striatal perfusate decreased. The AMPA-induced increase in dopamine levels was suppressed significantly by the systemic administration of NBQX (40 mg/kg, i.p.). Perfusion with tetrodotoxin (TTX, 5 microM) alone reduced the basal level of dopamine by 80%. Perfusion with 1.0 mM AMPA together with TTX produced a 3.9-fold increase in dopamine efflux from the TTX reduced basal level. However, the maximum dopamine level obtained thereby was close to the basal level of dopamine seen prior to perfusion with TTX. The present results demonstrate that AMPA receptors participate in tonic facilitative modulation of striatal extracellular level of dopamine. In addition, the results support the view that glutamatergic neurons modulate the release of dopamine via subtypes of excitatory amino acid receptors in the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Temporal pattern of AP-1 DNA-binding activity in the rat hippocampus following a kindled seizure.

DNA binding by transcripton factor AP-1 was enhanced remarkably following kindling stimulation in rat amygdala. Maximum increase occurred 2 h after stimulation with return to baseline within 24 h. Supershift and western analyses revealed that 38,000 mol. wt Fos-related antigen and JunD were the main components of the evoked AP-1 complexes at the time their induction reached maximum. AP-1 induction 2 h after the last kindling stimulation was more prominent in samples from previously kindled rats than in those from non-kindled rats. This study sought to establish the role of AP-1 in plastic changes of the hippocampus associated with kindling. Male Sprague-Dawley rats were kindled from the left amygdala until they exhibited Racine15 class 5 generalized seizures. Nuclear proteins were extracted from dorsal hippocampi obtained from 0 to 24 h after final stimulations. From these, we evaluated the temporal pattern of DNA binding by AP-1 using a gel mobility-shift assay with a 32P-labelled AP-1 probe. Supershift and western analyses were added to investigate components of the seizure-evoked AP-1 complexes. Our results suggest that the basal level of AP-1 complexes is not associated with the seizure susceptibility in kindling. However, development of kindling appears to facilitate stimulus-evoked AP-1 induction, probably via plastic changes in the central nervous system. AP-1 may mediate such changes by regulating expression of certain genes.

Analysis of Variance↗
PubMed1997

Increased levels of mRNA for beta- but not alpha-subunit of calmodulin kinase II following kindled seizures.

We studied levels of mRNA for the alpha- and beta-subunits of calmodulin (CaM) kinase II using the amygdaloid kindling model of epilepsy. There were significant increases in mRNA for the beta-subunit of CaM kinase II in the hippocampus 4-24 h after stage 5-kindled seizures. Moreover, this mRNA was significantly increased by 20.0-26.5% in the bilateral dentate gyrus 8 to 24 h after kindled seizures. The beta-subunit mRNA was also significantly increased by 13.5-19.0% in the CA3 on the side ipsilateral to the stimulation, 4 to 8 h after kindled seizures. mRNA for the alpha-subunit of CaM kinase II was not significantly changed in the regions examined for up to 24 h after the kindled seizures. These results suggest that CaM kinase II mediates the molecular processes that follow kindled seizures. It is possible that increases in CaM kinase II-dependent protein phosphorylation are associated with the plastic changes in kindling.

Animals↗
PubMed1997

Polymorphism of dopamine receptors and transporter genes in neuropsychiatric diseases.

The advances made in studies on the molecular biology of the dopamine transporter (DAT) and receptors (D1, D2, D3, D4 and D5) are reviewed, and their pharmacological characteristics and the relationship between polymorphic variations of these human proteins and neuropsychiatric disorders are discussed. Data from four studies on the variants of the D2 receptor gene (Ser311-->Cys). BalI polymorphism in D3, 48-base repeat polymorphism in D4, and 40-base repeat polymorphism in the DAT gene in patients with schizophrenia, mood disorder, neurological disease and controls are reported.

Carrier Proteins↗
PubMed1997

Noninsulin-dependent diabetes mellitus-related encephalopathy presenting with amnesia, personality change, and autonomic seizure.

We describe a patient with noninsulin-dependent diabetes mellitus presenting with an amnestic disorder, personality change, and autonomic seizure. Magnetic resonance images of the brain showed T2-high signal lesion in the hippocampi bilaterally and nonspecific white matter disease, while single photon emission computed tomography revealed a diffuse reduction of cerebral blood flow. Sensory and auditory evoked potentials revealed delayed impulse conduction velocities in the central nervous system. Degenerative changes caused by a microvascular angiopathy related to noninsulin-dependent diabetes mellitus may underlie the central nervous system manifestations in our patient.

Action Potentials↗
PubMed1997

[A man with systemic lupus erythematosus presenting with spastic paraplegia].

We report a 38-year-old man systemic lupus erythematosus who presented with an acute onset of paraplegia and urinary retention. The man had a 12-year history of nodular cutaneous mucinosis and arthralgia. In 1994, he was admitted to our hospital with a sudden onset of weakness and numbness of the right leg followed by an emergence of similar symptoms in the left leg. His elder sister had died at 16 years of age after suffering from systemic lupus erythematosus for 6 years. On examination, the patient had skin rash on his chest, back, head, forehead, and extremities. The neurological examination revealed that his tongue deviated to the right on protrusion. The muscle power was reduced to 2-3/5 in the right leg and to 4/5 in the left leg. The sensory disturbance was noted in the lower extremities with predominant involvement of the right leg. Reflexes were increased in the right biceps, triceps, both patellas, and Achilles tendons. Babinski sign was noted bilaterally. Urinary retention and constipation were also noted. The results of the blood cell count and hepatic and renal function tests were normal. Serum levels of C-reactive protein and complements (C3, C4, CH50) were also normal. Serological examinations showed increased anti-DNA antibody (14 U/ml, [normal, < 6]). Antinuclear antibody was positive at a titer of 1:1380. CSF study showed an increased protein concentration of 83 mg/dl and an IgG level of 14 mg/dl with a normal number of cells. MR images revealed a T1-low, T2-high signal lesion at the upper part of the left ventral medulla. MR images of the brain and spinal cord were normal. The patient was diagnosed as having SLE. High-dose intravenous methylprednisolone (1 g/day) pulse treatment that was started 25 days after the onset of neurological symptoms, produced partial relief. Our case presented with paraplegia with a focal lesion in the left upper ventral part of the medulla on MR images. The incidence of male SLE is low, and paraplegia is a rare complication of SLE. Thus, the medullary lesion in SLE observed in our case appears to be rare. SLE should be considered as a cause of acute onset paraplegia or myelopathy.

Adult↗
PubMed1997

[A case of idiopathic orthostatic hypotension with selective involvement of postganglionic noradrenergic neurons].

A 44-year-old man had a 30-year history of orthostatic hypotension and diarrhea. One month before admission, he suddenly lost consciousness by defecation, and was hospitalized. He became alert within two days, but he could not sit up due to severe orthostatic hypotension. At that point, he was transferred to our hospital. On admission, talipes and microdactylia were noted. Neurological examination revealed brisk patellar tendon reflexes. Anhidrosis or impotence was not present. Analyses of blood and urine yielded normal results. Cardiological examination revealed no abnormality that could be responsible for the hypotension. MR images of the brain were also normal. However, single photon emission tomography revealed diffuse hypoperfusion of the brain. A head-up tilt (50 degrees) test induced a remarkable fall in systolic blood pressure from 149 (heart rate; 65/min) to 64 mmHg (83). Immersion of hand in ice-cold water failed to increase blood pressure. Heart rate variation and cystometry results, which represent the function of parasympathetic nerves, were normal. Warming of his body caused normal sweating. Intravenous injection of low doses of norepinephrine and methoxamine increased blood pressure while isoproterenol remarkably increased heart rate, suggesting that both alpha- and beta-receptors developed supersensitivity. Instillation of 5% cocaine and 5% tyramine into the conjunctival sac failed to cause pupillary dilation. Clinical findings and pharmacological challenge test results suggested that the main lesion of his autonomic nervous system was selectively confined to the postganglionic sympathetic nerves and noradrenergic (not cholinergic) neurons. The autonomic failure of our patient can be classified as idiopathic orthostatic hypotension. However, most patients with idiopathic orthostatic hypotension or pure autonomic failure complain of anhidrosis and impotence, which were not noted in our patient. These symptomatic differences may be the result of the highly selective involvement of noradrenergic neurons in the postganglionic sympathetic system in our patient.

Adult↗
PubMed1996

Effect of acute and chronic administration of methamphetamine on activator protein-1 binding activities in the rat brain regions.

The activator protein-1 (AP-1) binding activities in the three brain regions (striatum, nucleus accumbens, cingulate cortex) increased after a single methamphetamine (METH, 4 mg/kg) injection and reached maximum levels after 180 min. Pretreatment with SCH 23390 (0.5 mg/kg), a selective dopamine D1 receptor antagonist, significantly inhibited the enhanced AP-1 binding activities induced by acute METH (4 mg/kg) administration. In chronic experiments, rats were pretreated with METH (4 mg/kg) or saline for 14 days. The AP-1 binding activities after a 1-week abstinence from chronic administration of MAP increased significantly in all the brain regions compared with those of the saline-treated controls, whereas after a 4-week abstinence, the AP-1 binding activity decreased significantly in the cingulate cortex, but not striatum or nucleus accumbens, compared with the saline-treated control group. A METH challenge after a 4-week abstinence period induced significantly more intense stereotypy, but lower AP-1 binding activities in all the brain regions of rats treated with repeated METH than repeated saline injections. The super-shift assay revealed that after a 1- or 4-week abstinence, there was no significant difference between the Fos-related antigens (Fras) contents of the saline- and METH-treated groups in any brain region examined, and that the Jun family protein levels of the METH-treated group increased significantly in the striatum and nucleus accumbens after a 1-, but not 4-, week abstinence. These results suggest that chronic METH administration leads to delayed decay of the induced AP-1 binding activities and Jun component levels after abstinence for up to 1 week, but results in no change in or decreases these activities and attenuates METH challenge-induced AP-1 binding activities after abstinence for 4 weeks.

Animals↗
PubMed1996

Levodopoa but not bromocriptine induces AP-1 and creb DNA-binding activity in the dopamine-depleted striatum of the rat.

To elucidate the neurochemical mechanism that underlies the effect of anti-parkinsonian agents on motor activities in the dopamine-depleted striatum, we evaluated AP-I and CREB DNA-binding activity in the striatum of 6-hydroxydopamine-lesioned rats by use of a gel mobility-shift assay. Rats with a unilateral lesion of the nigrostriatal dopamine pathway were injected i.p. with either SKF38393 (a DI receptor agonist), bromocriptine (a D2 receptor agonist), or levodopa (a Dl/D2 receptor agonist). Each treatment increased the number of rotational responses of rats contralateral to the lesioned side. However, only SKF38393 and levodopa increased AP-I and CREB DNA-binding activity in the dopamine-depleted striatum. As with the expression of c-fos, supersensitive DI receptors may play a key role in the enhanced induction of AP-I and CREB DNA-binding activity in the dopamine-depleted striatum. Supershift analysis revealed that c-Fos; and Jun family proteins are the main components for AP-1 induced in the dopamine-depleted striaturn by SKF38393 or levodopa.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Synergistic effect of D1 and D2 dopamine receptors on AP-1 DNA-binding activity in the striatum and globus pallidus of the rat with a unilateral 6-OHDA lesion of the medical forebrain bundle.

The synergistic effect of D1 and D2 dopamine receptors on transcription factor AP-1 was studied in the striatum and globus pallidus of rats with unilateral 6-OHDA lesions of the medial forebrain bundle. Contralateral rotational behavior in response to a challenge dose of D1 agonist with and without D2 agonist was determined by behavioral observation, and AP-1 induction was studied by a gel mobility-shift assay. Single administration of vehicle and of a low dose of the D1 agonist (SKF38393, 0.5 mg/kg, i.p.) failed to induce rotational behavior, while the D2 agonists bromocriptine (2.5 mg/kg, i.p.) and quinpirole (1 mg/kg. i.p.) induced low rate rotations. High dose of SKF38393, 10 mg/kg, i.p., and low dose D1 and D2 agonists administered together induced a higher rate of rotation. The gel mobility-shift assay also suggested a synergistic interaction between D1 and D2 receptors on AP-1 induction in both the striatum and globus pallidus ipsilateral to the 6-OHDA lesioned nigrostriatal pathway. However, the mode of AP-1 induction via each dopamine receptor subtype appeared to differ between these brain structures. Thus, in the striatum of the lesioned side, single administration of a high dose of D1 agonist, and combined administration of D1 agonist with either of the D2 agonists resulted in AP-1 induction, while in the globus pallidus, AP-1 binding was induced by the D2 agonist bromocriptine and combined administration of a low dose D1 agonist with D2 agonists, but not by D1 agonist alone, even at a high dose. These results demonstrate that a D1/D2 dopamine receptor synergism is involved is the induction of AP-1 both in the striatum and globus pallidus of the rat with ipsilateral dopamine depletion. The induction of AP-1 via each receptor subtype appears, however, to be differently regulated in these two structures.

Animals↗
PubMed1996

Activator protein-1 binding activities in discrete regions of rat brain after acute and chronic administration of methamphetamine.

The activator protein-1 (AP-1) binding activities increased in three brain regions (striatum, nucleus accumbens, and cingulate cortex) after a single methamphetamine (METH) injection to rats. Pretreatment with SCH 23390, but not (-)-eticlopride, significantly inhibited the enhanced AP-1 binding activities induced by acute METH administration. The magnitude of enhancement of AP-1 binding activities 3 h after the last dose of chronic METH administration (4 mg/kg once daily for 14 days) was significantly attenuated as compared with those 3 h after a single METH administration. The AP-1 binding activities after a 1-, but not 4-, week abstinence from chronic administration of METH were still significantly higher than those of the saline-treated controls. A METH challenge after a 4-week abstinence period induced significantly lower AP-1 binding activities in rats chronically injected with METH than in rats chronically injected with saline. The supershift assay revealed that the levels of Jun family protein, but not Fos-related antigen, increased significantly in the striatum and nucleus accumbens of chronically METH-treated rats after a 1-week abstinence. These results suggest that chronic METH administration leads to delayed decay of the induced AP-1 binding activities and Jun component levels after abstinence for up to 1 week but results in no change in or decreases these activities and attenuates METH challenge-induced AP-1 binding activities after abstinence for 4 weeks.

Animals↗
PubMed1996

Regional increases in brain-derived neurotrophic factor and nerve growth factor mRNAs during amygdaloid kindling, but not in acidic and basist growth factor mRNAs.

We studied mRNA levels for neurotrophic factors using the amygdaloid k indling model of epilepsy. One hour after stage 5 kindled seizures, there were four-to fivefold increases in brain-derived neurotrophic factor (BDNF) mRNA in rat dentate gyrus and perirhinal cortex. Nerve growth factor (NGF) mRNA levels were increased bilaterally in some (but not all) limbic areas. There were no detectable changes in acidic fibroblast GF (aFGF) mRNA or basic fibroblast GF (bFGF) mRNA for 24 h after the kindled seizures. During kindling, levels of BDNF mRNA in the dentate gyrus correlated with projection to generalized seizures, whereas NGF mRNA in the limbic regions continued to increase during seizure development. These results indicate that the induction of mRNAs for neurotrophic factors, especially for BDNF mRNA in the dentate gyrus, corresponds to the increases in metabolic and electrical ictal discharge associated with kindled seizures. The persistent increase observed in NGF mRNA may be related to enhanced synaptic efficacy during kindling, but aFGF and bFGF are presumed to have little relation to the kindling process.

Amygdala↗
PubMed1996

[Myocardial metastasis in the right ventricle from uterine cervical carcinoma with high 67Ga-citrate accumulation: a case report].

We report a case of high 67Ga-citrate accumulation with myocardial metastasis in the right ventricle from uterine cervical carcinoma. A 41-year-old woman was admitted to our hospital because of acute abdomen after operation and radiotherapy for uterine cervical carcinoma. On performing 67Ga-scintigraphy for differentiation from fever of unknown origin, we found significant 67Ga-citrate accumulation in the right ventricle. To the best of our knowledge, this is a rare case.

Adult↗
PubMed1996

[A case of recurrent squamous cell carcinoma of cervix successfully treated with BOMP].

Combination chemotherapy consisting of bleomycin, vincristine, mitomycin C and cisplatin (BOMP) was applied to a case (57 years old) with recurrence of squamous cell carcinoma of the cervix. The patient with FIGO stage IIIb cervical carcinoma had been treated with radiotherapy seven years ago. She was affected by malignant pericardial effusion, and was treated with direct intrapericardial administration of cisplatin (20 mg). After instillation, ultrasonography and computed tomography showed the wall thickening of colon and marked ascites. Barium enema showed the circumferential narrowing and serrations of colon, and it was diagnosed to be carcinomatous peritonitis. She was treated with BOMP consisting of BLM (5 mg, i.m., days 1 - 5), VCR (1 mg, i.v., day 5'), MMC (8 mg, i.v., day 5), and CDDP (70 mg, d.i.v., day 5). After three courses of BOMP therapy, she achieved a complete response with few toxic effects and did not require special care. She has been free of disease for six months and her performance status is 0. This encouraging result warrants the use of this combination chemotherapy regimen in other patients with recurrent squamous cell carcinoma of the cervix.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Levodopa induces AP-1 and CREB DNA-binding activities in the rat striatum.

In order to elucidate the effect of levodopa and bromocriptine on the DNA-binding activities of transcription factors, AP-1 and CREB DNA-binding activities were investigated using gel-shift assay. Intraperitoneal administration of 100 mg/kg levodopa with 50 mg/kg benserazide in rats increased both AP-1 and CREB DNA-binding activities in the dorsolateral aspect of the striatum. The major proteins composing the increased AP-1 were JunB and JunD. Bromocriptine at doses of 2.5 and 5.0 mg/kg, however, did not increase these binding activities. Present results suggest that levodopa but not bromocriptine induces these transcription-regulating proteins in the striatum with normal dopaminergic functioning.

Animals↗
PubMed1995

Does homozygosity advance the onset of dentatorubral-pallidoluysian atrophy?

We confirmed a homozygous type of relatively small expansion of CAG triplet repeats (57 repeats) in the short arm of chromosome 12 in a male patient with dentatorubral-pallidoluysian atrophy (DRPLA) by polymerase chain reaction. He showed early onset (age, 17 years) of DRPLA. There was good correlation of the age of onset with the number of triplet repeats. The homozygous state of the expansion of the triplet repeats was responsible for the early onset and severity of his DRPLA.

Adult↗