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Biomedical subjects

H Ujike

Publications and source records attributed to H Ujike.

At least 73 records · Page 4Linked to original sources
PubMed1992

BMY-14802 reverses the reduction of striatal dopamine release induced by (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine.

Intraperitoneal injection of (+)-3-[3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), a sigma receptor agonist, significantly reduced the striatal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) measured by in vivo microdialysis. These reductions were significantly greater at (+)-3PPP doses of 12 and 24 mg/kg than at 1 mg/kg. The levels of 5-hydroxyindoleacetic acid (5HIAA) were increased by the injection of (+)-3PPP in dose of 24 mg/kg, but were not affected at lower doses. BMY-14802, a sigma antagonist, alone at doses of 15 mg/kg and 30 mg/kg did not affect the levels of DA, DOPAC, HVA and 5HIAA. Pretreatment with 30 mg/kg BMY-14802 reversed the reduction of the levels of DA induced by 12 mg/kg (+)-3PPP. Although neither 30 mg/kg BMY-14802 nor 12 mg/kg (+)-3PPP affected the levels of striatal 5HIAA, combined treatment with both produced a significant elevation. These findings clearly demonstrate that sigma receptors may regulate DA release from the striatal presynapse.

Animals↗
PubMed1992

Supersensitivity of sigma receptors after repeated administration of cocaine.

We investigated the role of sigma receptors in the expression of behavioral sensitization induced by cocaine. Rats received intraperitoneal injections of either 20 mg/kg cocaine or saline once daily for 14 consecutive days. Cocaine-treated rats became sensitized. After a 5-day abstinence period, a challenge dose of (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was administered. (+)-3-PPP at doses of 12 and 24 mg/kg induced significantly more frequent rearing and more potent stereotypy consisting of repetitive head movement and sniffing in cocaine-sensitized rats than in saline-pretreated rats. These enhanced responses to (+)-3-PPP lasted for at least a month. The enhanced responses to (+)-3-PPP were attenuated by 30 mg/kg BMY 14802, a putative sigma antagonist, and also attenuated by 100 mg/kg (+/-)-sulpiride, a D2 dopamine antagonist. These findings show that repeated administration of cocaine produces lasting supersensitivity of simga receptors, which may induce subsequent activation of dopaminergic transmission.

Animals↗
PubMed1992

Competitive and non-competitive N-methyl-D-aspartate antagonists fail to prevent the induction of methamphetamine-induced sensitization.

In order to elucidate the possible roles of the glutamate system in the mechanisms underlying behavioral sensitization, which is used as an animal model for human psychosis, we investigated the effects of 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and MK-801 ((+)-dizocilpine), a competitive and noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, respectively, on methamphetamine-induced behavioral sensitization in rats. Administration of 0.5 mg/kg MK-801 enhanced 2 mg/kg methamphetamine-induced hyperactivity, whereas it reduced 6 mg/kg methamphetamine-induced stereotyped behavior markedly. CPP (10 mg/kg) reduced 2 mg/kg methamphetamine-induced stereotypy slightly. Repeated treatment with 2 and 6 mg/kg methamphetamine alone induced progressive augmentation of stereotypy, whereas combining either MK-801 or CPP with methamphetamine treatment abolished or attenuated this augmentation. However, when rats were challenged with methamphetamine after a 7-day period of abstinence, the intensity of stereotypy among the rats pretreated with repeated doses of methamphetamine alone or in combination with MK-801 or CPP did not differ significantly. These results indicate that competitive and non-competitive NMDA receptor antagonists modulate acute methamphetamine-induced abnormal behavior and sensitization expression, but they failed to prevent the induction of the neural mechanisms underlying behavioral sensitization.

Animals↗
PubMed1992

Sigma (sigma) antagonist BMY 14802 prevents methamphetamine-induced sensitization.

We have demonstrated for the first time that the sigma antagonist BMY 14802 prevents the development of behavioral sensitization induced by repeated administration of methamphetamine. Rats received an intraperitoneal injection of 15 or 30 mg/kg BMY 14802 followed by 2 mg/kg methamphetamine 30 min later. Unlike dopamine antagonists, BMY 14802 did not induce major changes in the acute motor effects of 2 mg/kg methamphetamine. Repeated administration of methamphetamine induced progressive augmentation of stereotyped behaviors and resulted in behavioral sensitization. However, repeated administration of methamphetamine in combination with BMY 14802 at either dose produced no increase in the intensity of stereotypy when compared with the first treatment. After a 7-day abstinence period, a challenge test with methamphetamine alone revealed supersensitivity of methamphetamine-sensitized rats to subsequent methamphetamine, whereas rats pretreated with repeated methamphetamine in combination with BMY 14802 exhibited no difference in the intensity of stereotypy from rats pretreated with repeated saline. These results suggest that sigma receptors play a crucial role in the induction of methamphetamine-induced sensitization.

Animals↗
PubMed1992

Voluntary intake of alcohol is attenuated by ipsapirone in mice and role of 5-HT1A receptor.

Emerging evidences have suggested that the brain serotonin (5-hydroxytryptamine, 5-HT) neurotransmitter system is involved in the compulsive alcohol-seeking behaviors in humans and animal models. The aim of this study is to examine the effect of ipsapirone, which is a specific 5-HT1A agonist with a pyrimidinylpiperazine structure, on alcohol consumption in mice (C57BL/6J) by a voluntary alcohol intake paradigm. When the consumed alcohol was expressed as g/kg B.W., the total 12-day amount was significantly lower in the ipsapirone-treated mice than in the saline-treated mice. However, 5-HT1A receptor binding sites labeled with [3H]8-OH-DPAT in hippocampal membranes did not differ significantly in either the total number of binding sites (Bmax) or dissociation constant (Kd) between the two groups. The possible mechanism regarding the role of ipsapirone that attenuated the alcohol consumption, and its relationship to the subtyping 5-HT receptors are further discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

[CSF monoamine metabolites in patients with progressive supranuclear palsy].

Neurochemical abnormalities in the patients with progressive supranuclear palsy (PSP) are not well understood. We investigated CSF levels of the monoamine metabolites HVA, 5HIAA and MHPG in 5 patients with PSP in order to investigate, especially dopaminergic, serotonergic and noradrenergic metabolism. Results were as follows (value; mena +/- S.D.). [table: see text] The levels of HVA were significantly lower than those in controls. These findings suggest that there is a hypofunction of dopaminergic neurons in PSP patients.

Aged↗
PubMed1992

[Diffuse reduced uptake in 99m-Tc-HM-PAO SPECT and high level of neuron-specific enolase in cerebrospinal fluid in the early stage of Creutzfeldt-Jakob disease].

We report an autopsy-diagnosed case of Creutzfeldt-Jacob disease (CJD) showing diffuse reduced uptake in SPECT and a high level of neuron-specific enolase (NSE) in the cerebrospinal fluid (CSF). A 75-year-old woman with a 3-month history of progressive gait ataxia and dementia was examined. Four months after onset of the disease, she developed an akinetic mutism with normal CT and MRI. She was admitted for further examination, and electroencephalography showed periodic synchronous discharges. NSE in the CSF showed a high level at 90.6 ng/ml, and SPECT showed diffuse reduced uptake in the supratentorial region, with relatively spared uptake in the cerebellum. She died 13 months after onset of the disease, and the autopsy diagnosis was CJD. SPECT data and the level of NSE in CSF seem to be useful for clinical diagnosis and pathogenetic analysis in the early stage of CJD.

Aged↗
PubMed1991

Co-administration of either a selective D1 or D2 dopamine antagonist with methamphetamine prevents methamphetamine-induced behavioral sensitization and neurochemical change, studied by in vivo intracerebral dialysis.

Repeated administration of amphetamine or methamphetamine (MAP) causes behavioral sensitization in animals. Recently, several studies have revealed that in vivo release of dopamine from presynaptic nerve terminals of mesotelencephalic dopamine neurons is enhanced when sensitized animals are rechallenged with a psychostimulant. The present study investigated the effect of co-administration of SCH 23390 (a selective D1 dopamine receptor antagonist) or YM-09151-2 (a selective D2 dopamine receptor antagonist) prior to each MAP injection for 14 days on dopamine efflux in the striatal perfusates using in vivo dialysis. After 3 months drug abstinence, MAP challenge alone produced augmented stereotypy in the MAP group, but not in the control, the SCH 23390 + MAP or the YM-09151-2 + MAP group. In parallel with this behavioral observation, the degree to which dopamine efflux increased following the MAP challenge was significantly greater in the MAP group than that in the control, SCH 23390 + MAP group and the YM-09151-2 + MAP groups. While dopamine efflux after MAP challenge did not differ between the control and the YM-09151-2 + MAP group, it was greater in the SCH 23390 + MAP group than the control group. These results indicate that both D1 and D2 dopamine receptors play a role in the formation of behavioral sensitization, but with different mechanisms.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Lasting increase in D1 dopamine receptors in the lateral part of the substantia nigra pars reticulata after subchronic methamphetamine administration.

To examine the possible involvement of D1 dopamine receptors in behavioral sensitization induced by subchronic methamphetamine (MAP) administration, regional D1 receptors labeled with [3H]SCH 23390 were examined using binding assay and quantitative autoradiography. Rats received 4 mg/kg/day MAP (i.p.) for 14 days, and were decapitated after an abstinence period of 24 h, 7 days or 21 days. In MAP-treated rats, a significant decrease in Kd in the mesolimbic area was observed 24 h but not 7 days after the last injection. Neither Kd nor Bmax changed in the striatum or medial prefrontal cortex of MAP-treated rats after any period of abstinence. Autoradiography revealed a significant increase in specific [3H]SCH 22390 binding in the lateral part of the substantia nigra pars reticulata (SNr) of MAP-treated rats. Since this increase lasted up to 21 days after cessation of subchronic MAP administration, it is suggested that lasting increase in the nigral D1 receptors may be associated with the biological changes underlying MAP-induced behavioral sensitization.

Animals↗
PubMed1991

[A rare case of adult-onset Becker muscular dystrophy diagnosed by dystrophin staining].

Different diagnosis of Becker muscular dystrophy (MD) from limb-girdle MD mainly depends on the differences of heredity form and age at onset. However, sporadic cases with either type of MD often occur, and occasionally Becker MD can occur in adult age when limb-girdle MD commonly occurs. We reported the male sporadic case of Becker MD with the onset at 30 year old who was diagnosed by dystrophin staining. At the age of 30, he noticed mild difficulty to stand up and instability when hurrying up stairs. His weakness of lower limb-girdle gradually progressed, but he is able to walk without any support at the present age of 54, and he never showed weakness in upper limbs. Neurological and laboratory examination revealed that severe atrophy of lower limb-girdle, mild calf hypertrophy and moderate elevate of serum CK level. These history and symptoms hardly distinguish between Becker and limb-girdle MD. Immunostaining of biopsy muscle from the patient using the antiserum against synthetic peptide fragment of dystrophin revealed faint and patchy pattern, and immunoblot revealed 380 kd of abnormal size dystrophin. These dystrophin testing confirmed that this case was a rare case of Becker MD with adult-onset and mild clinical course.

Dystrophin↗
PubMed1990

In situ hybridization of muscle mitochondrial mRNA in mitochondrial myopathies.

To determine whether a mitochondrial mRNA deficiency exists in mitochondrial myopathies, muscle biopsies from a patient with chronic progressive external ophthalmoplegia (CPEO) and a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) were studied using in situ hybridization. Histochemistry and immunohistochemistry were performed along with hybridization. Hybridization reactions were widely distributed over the sarcoplasm of all muscle fibers in the patient with MELAS. In the patient with CPEO, 80% of the fibers showed a marked decrease in density of autoradiographic grains. This marked decrease corresponded to the histochemical and immunohistochemical findings of a very weak staining of cytochrome c oxidase (CCO). The isotope-labeled cDNA probe used in in situ hybridization in this study complements a part of subunit I of CCO and a part of subunit II of complex I in the mitochondrial gene. Our results suggest a defect in the mRNA in this CPEO patient.

Adult↗
PubMed1990

D-2 but not D-1 dopamine agonists produce augmented behavioral response in rats after subchronic treatment with methamphetamine or cocaine.

A study was performed to examine behavioral response to a challenge of selective dopamine D-1 and D-2 agonists in rats previously sensitized by subchronic administration of methamphetamine or cocaine. Rats in three groups received repeated injections (IP) of saline, methamphetamine (4 mg/kg/day) or cocaine (20 mg/kg/day), respectively, for 14 days. After an abstinence period of 7-13 days, all groups were challenged with either a selective D-1 agonist (SKF 38393) or D-2 agonists (quinpirole or RU 24213). The ability of SKF 38393 (6 mg/kg or 18 mg/kg) to produce grooming behavior did not differ significantly among the saline-, methamphetamine- and cocaine-treated groups. In contrast, quinpirole (1 mg/kg) and RU 24213 (3 mg/kg) produced more intense stereotypy consisting of rearing, sniffing and repetitive head movement in the two psychostimulant-treated groups than in the saline-treated group. Such augmented response to selective D-2 agonists was observed even after a 1-month abstinence period. These results suggest that the enduring behavioral sensitization induced by two pharmacologically distinct psychostimulant agents, methamphetamine and cocaine, occurs through a common neurobiological mechanism of lasting supersensitivity in postsynaptic D-2, but not D-1 dopamine receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

A case of bulbospinal muscular atrophy with chief complaint of sensory disorder in the lower extremities.

A 56-year-old man was admitted to our department with a chief complaint of lower extremity dysesthesia. He described a dull numbness below the ankle and a dull pain in the nates for the past two years. Although the numbness extended to the thigh, he did not notice any muscular weakness or atrophy. Neurological examination revealed weakness and atrophy in the face, tongue and the proximal portions of all four extremities. Deep tendon reflexes were decreased. A moderate loss of vibratory sensation was noted below the knees. Electromyography showed neurogenic changes. Muscle biopsy revealed both myogenic and neurogenic changes. Sural nerve biopsy revealed a mild reduction of myelinated fibers, particularly the large-diameter fibers. Based on these findings, a diagnosis of bulbospinal muscular atrophy (BSMA) was made. In recent years, there have been some case reports of BSMA with sensory disturbances, or merely with subclinical manifestations of a sensory disturbance. This case is included in the same category as those reports, but it is interesting to note that the sensory disturbance in the lower extremities occurred as the chief complaint of the disease.

Humans↗
PubMed1990

Senile delirium with special reference to situational factors and recurrent delirium.

Factors initiating senile delirium were examined in 129 elderly inpatients (65 years or older). Sixty-eight patients were males and 61 females, with a mean age of 76.3 years. Delirium developed in most cases on the first two days of admission in the hospital, and the admission appeared to be a key factor precipitating delirium in about 30% of the patients. Delirium resolved or improved in 80% of the patients, but usually persisted in patients with dementia. Senile delirium tended to reappear repeatedly in patients whose episode of delirium lasted for more than 2 weeks, was associated with dementia, or had a prior history of delirium.

Aged↗
PubMed1989

Effects of selective D-1 and D-2 dopamine antagonists on development of methamphetamine-induced behavioral sensitization.

The present study examined effects of selective antagonists of D-1 and D-2 dopamine receptors on the development of behavioral sensitization produced by repeated methamphetamine (MAP) administration. Male Sprague-Dawley rats were divided into four groups. Each group received a daily injection of saline (control group), 4 mg/kg MAP (MAP group), 1 mg/kg YM-09151-2 plus 4 mg/kg MAP (YM + MAP group) or 0.5 mg/kg SCH 23390 plus 4 mg/kg MAP (SCH + MAP group) for 14 days. During daily injection for 14 days, the MAP group exhibited a progressive augmentation in locomotor and stereotyped behavior, whereas the progression of such behaviors in the YM + MAP and SCH + MAP group was completely prevented. After an abstinence period of 7 days, all groups received a challenge of 2 mg/kg MAP. The MAP challenge reproduced hyperlocomotion and intense stereotyped behavior only in the MAP group. However, neither the YM + MAP group nor the SCH + MAP group showed stereotypy. The manner in which both groups showed only hyperlocomotion was similar to that observed in the control group. These results indicate that both selective D-1 antagonists and selective D-2 antagonists not only reverse MAP-induced motor effects at each injection but also prevent the development of behavioral sensitization induced by repeated MAP administration.

Animals↗
PubMed1989

[Ultrastructural immunocytochemical localization of electron-transport enzymes in mitochondrial myopathy].

Ultrastructural localization of mitochondrial electron transport enzymes in biopsied muscle from a patient with mitochondrial myopathy was studied. We applied the immunoelectron microscopic technique using colloidal-gold labeled antibodies. The results demonstrated a very distinct and dense labeling by gold particles of complexes I, III, and IV in the inner mitochondrial membrane. The density of gold particles reacted to complex IV was cleanly decreased. This result was correlated with the decreased biochemical activity of complex IV. Labeling on the paracrystalline inclusions was substantially decreased in abnormal giant mitochondrial, but gold particles were extensively confined on the membrane of cristae surrounding the inclusions.

Adult↗