Biomedical subjects

H Uchimura

Publications and source records attributed to H Uchimura.

At least 37 records · Page 2Linked to original sources

PubMed1995

The effect of phencyclidine on the basal and high potassium evoked extracellular GABA levels in the striatum of freely-moving rats: an in vivo microdialysis study.

The effect of phencyclidine (PCP) on the gamma-aminobutyric acid-ergic (GABAergic) transmission in the striatum of freely-moving rats was investigated using an in vivo microdialysis. The high potassium (100 mM) increased the extracellular GABA level to 4000% of the basal level. Although the basal GABA level in the striatal dialysate did not show either calcium dependency or tetrodotoxin (TTX) sensitivity, the high potassium evoked GABA level was reduced by 82% under calcium-free conditions (with 12.5 mM magnesium) and by 54% in the presence of 10 microM TTX. The systemic administration of PCP (7.5 mg/kg) or the local perfusion of PCP (100 microM and 1 mM) significantly inhibited the high potassium evoked GABA release in the rat striatum. The local perfusion of MK-801 (10 microM and 100 microM), a more potent and selective N-methyl-D-aspartate (NMDA) receptor antagonist, also inhibited the high potassium evoked striatal GABA release. These drugs did not show any significant effect on the basal extracellular GABA level. NMDA (1 mM) either partly or completely blocked the effect of PCP (1 mM) or MK-801 (100 microM) on the high potassium evoked striatal GABA release. On the other hand, nomifensine (100 microM), a dopamine uptake blocker, did not show any effect on the high potassium evoked GABA release. These results suggest that PCP inhibited the striatal GABAergic neuronal transmission through its antagonism of the NMDA receptor.

Animals↗

PubMed1995

Ischemia-induced release of amino acids in the hippocampus of aged hypertensive rats.

We have recently demonstrated the age-related vulnerability of hippocampal neurons to 20-min forebrain ischemia in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of aging on the release of amino acids in the hippocampus during transient cerebral ischemia for 20 min. Concentrations of extracellular amino acids and cerebral blood flow in the CA1 subfield were examined by an in vivo brain dialysis technique and a hydrogen clearance method, respectively, in adult (5-7 month) and aged (19-23 month) female SHR. During cerebral ischemia by bilateral carotid artery occlusion, cerebral blood flow to the hippocampus decreased to 20% of the resting values in both groups. After recirculation, both groups showed delayed hypoperfusion which was more prominent in the aged SHR. In the adult rats, concentrations of both aspartate and glutamate increased to approximately 8-fold of the resting values during ischemia. The elevation of these excitatory amino acids in the adult SHR was not significantly different from that in the aged rats. In contrast, the concentration of taurine increased 26-fold in the adult SHR but only 16-fold in the aged rats. Changes in other amino acids were not different between the two groups. These results indicate that an imbalance of excitatory and inhibitory amino acids, e.g., smaller release of taurine, during ischemia may, at least in part, contribute to the age-related vulnerability of hippocampal neurons to transient cerebral ischemia in SHR.

Aging↗

PubMed1995

Mortality in psychiatric patients, with a specific focus on cancer mortality associated with schizophrenia.

BACKGROUND: Higher mortality rates among psychiatric patients compared with the general population have been widely reported. On the other hand, lower cancer mortality for schizophrenics has been occasionally pointed out. Few studies from Japan have investigated mortality among psychiatric patients, and this study is the first large-scale follow-up in this country. METHODS: A total of 4980 patients admitted to a national mental hospital from 1948 through 1982 were followed up until 31 August 1985. The standardized mortality ratios (SMR) were calculated in comparison to the general population, using the person-years method. RESULTS: The SMR for total deaths and those for malignancy were as follows for males/females respectively: 2.55/3.02 and 0.84/1.37 for schizophrenia, 1.76/2.37 and 1.44/2.10 for depression, 2.45/3.04 and 1.18/1.82 for mania, 1.81/1.90 and 0.27/1.07 for neurosis, 5.55/4.33 and 1.85/3.34 for alcohol/drug abuse, and 3.65/3.57 and 1.01/0.72 for organic brain syndrome. CONCLUSIONS: The SMR for total deaths were significantly elevated in schizophrenia, depression, mania, neurosis, alcohol/drug abuse, and organic brain syndrome, respectively. The SMR for malignancy were not elevated nor lowered significantly in any of these disease categories. The SMR for stomach cancer in male schizophrenics was significantly lower (0.27; P < 0.05).

Cause of Death↗

PubMed1995

Involvement of dopamine D1 receptors in phencyclidine-induced behavioral stimulation in rats.

The effects of dopamine receptor antagonists on phencyclidine (PCP)-induced behaviors were examined in rats. Acute administration with PCP (7.5 mg/kg i.p.) produced various behavioral changes, such as increases of spontaneous activity, head-weaving, sniffing, rearing, back-pedaling, and ataxia. To determine which dopamine receptor subtypes were involved in mediating the PCP-induced behaviors, SCH 23390 (0.05 and 0.5 mg/kg), sulpiride (20 and 100 mg/kg), or haloperidol (0.05 and 0.5 mg/kg) were pretreated 30 min before PCP treatment (7.5 mg/kg). A higher dose of SCH 23390 significantly reduced the increase of spontaneous activity induced by PCP. Both doses of sulpiride did not affect the PCP-induced behaviors. A higher dose of haloperidol decreased the PCP-induced spontaneous activity, whereas a lower dose of haloperidol enhanced the activity. Ketanserin (0.5 and 5 mg/kg) did not alter any PCP-induced behaviors. These results suggest that the D1, but not D2, dopamine receptor subtype may be involved in the PCP-induced behavioral abnormality.

Animals↗

PubMed1995

[Present status and future of enzyme immunoassay--hormone].

Recently various non-radioisotopic immunoassays have been developed instead of radioisotopic assay and widely used in the laboratory. Enzyme immunoassay (EIA) is most popular in use including chemiluminescent enzyme immunoassay (CLEIA). At present few hormones (thyroid related and gonadotropic hormones) are measured by EIA with semi or full automatic analysers and satisfactory specificity and sensitivity were already obtained. However, most hormones are still measured by RIA or IRMA. EIA for these hormones should be developed. Standardization of reference interval and calibrators would also be needed for the compatibility between different assays.

Calibration↗

PubMed1994

Effect of phencyclidine on dopamine release in the rat prefrontal cortex; an in vivo microdialysis study.

The effect of phencyclidine (PCP) on the extracellular dopamine levels in the rat prefrontal cortex was investigated using an in vivo brain dialysis technique. PCP increased extracellular dopamine levels in the prefrontal cortex of freely-moving rats after the systemic (7.5 mg/kg i.p.) or the local injection (100 microM and 500 microM). The local injection of MK-801, which is a more selective and potent NMDA receptor antagonist than PCP also increased the extracellular dopamine levels (from 10 microM to 100 microM). These results suggest that part of the effect of PCP is attributable to its antagonist effect on the NMDA receptor.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

[Structure and function of the thyroid hormone receptor].

Cloning of the thyroid hormone receptor and its identification as a cellular counterpart of the viral oncogene v-erbA was a major breakthrough in the study of thyroid hormone action. However, contrary to our initial expectations, many astonishing findings which have accumulated since the receptor cloning, especially the presence of two receptor types, made the elucidation of the thyroid hormone action extremely complicated. In this paper, we mainly did a phylogenic comparison of the amino acid sequence between alpha- and beta-type receptor from Xenopus laevis to humans, hoping to obtain some clue to clarify the functional differences between these receptors. There are several consistent amino acid differences between alpha- and beta-receptor through species in the DNA binding domain, one of which is non-conservative and is located in the portion supposed to be critical to the protein-protein interaction. We believe that clarification of the physiological significance of the presence of two receptor types will facilitate the study of thyroid hormone action.

Amino Acid Sequence↗

PubMed1993

Isradipine attenuates the ischemia-induced release of dopamine in the striatum of the rat.

We examined the effect of isradipine, a blocker of L-type voltage-sensitive Ca2+ channels (VSCCs), on the ischemia-induced release of dopamine in the rat striatum. Perfusion of 200 micrograms/ml isradipine in the striatum did not alter extracellular dopamine concentrations monitored by microdialysis. However, a marked increase (145-fold) in dopamine level during forebrain ischemia, developed by bilateral carotid artery occlusion, was attenuated significantly by 37% by isradipine whereas the intensity of ischemia, monitored by striatal blood flow, was unchanged. These results suggest that isradipine attenuates the ischemia-induced release of dopamine via blockade of L-type VSCCs on dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Effect of phencyclidine on endogenous excitatory amino acid release from the rat anterior cingulate cortex--an in vivo microdialysis study.

The effect of systemically administered phencyclidine (PCP) on the extracellular concentration of aspartate (Asp) and glutamate (Glu) in the rat anterior cingulate cortex was investigated using in vivo microdialysis. PCP significantly reduced the K(+)-evoked release of Asp and Glu, while it had no effect on the basal efflux of Asp and Glu. These results suggest that PCP might inhibit excitatory amino acid (EAA) release through an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism.

Amino Acids↗

PubMed1993

Ischemia-induced changes in brain monoamine metabolism in aged spontaneously hypertensive rats.

Effects of aging on monoamine metabolism in transient cerebral ischemia were studied using adult and aged female spontaneously hypertensive rats (SHRs). Tissue monoamine contents in discrete brain areas were quantified after 20 min of cerebral ischemia with or without 30-min recirculation. Cerebral blood flow (CBF) was determined with a hydrogen clearance method in separate experiments. Dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents in the striatum, nucleus accumbens and septum decreased in ischemic aged SHRs, compared with those in ischemic adult SHRs. After 30-min recirculation, DA contents were actually unchanged with inconsistently increased DOPAC levels. Ischemic CBF decreased to < 20% of the resting CBF in the striatum and cortex, which was not different between the two age groups of SHRs. These results indicate that aging is primarily responsible for more severely impaired DA metabolism during cerebral ischemia in aged SHRs.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Cerebral blood flow and ischemia-induced neurotransmitter release in the striatum of aged spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: We found age-related vulnerability to cerebral ischemia in the hippocampus and striatum in spontaneously hypertensive rats. Further study revealed that ischemia-induced release of hippocampal taurine, an inhibitory amino acid, was reduced by 40% in aged rats compared with adult rats, which suggested an impaired inhibitory function against excitotoxicity in aged rats. The purpose of this study was to examine whether ischemia-induced neurotransmitter release is altered in the striatum of aged spontaneously hypertensive rats. METHODS: Five adult (5-6 months) and five aged (18-22 months) female spontaneously hypertensive rats were subjected to 20 minutes of cerebral ischemia induced by bilateral carotid artery occlusions and 120 minutes of recirculation under amobarbital anesthesia (100 mg/kg i.p.). Cerebral blood flow was determined using the hydrogen clearance method, and extracellular concentrations of neurotransmitters were determined with the brain dialysis technique in the striatum. RESULTS: During ischemia, cerebral blood flow in aged rats decreased to 8.7 +/- 1.2 (mean +/- SEM) mL/100 g per minute (11% of the resting), which was not different from 5.2 +/- 1.7 mL/100 g per minute (8% of the resting) in adult rats, and extracellular dopamine and amino acids (glutamate, aspartate, and taurine) increased by approximately 170- and 10-30-fold, respectively, and returned to baseline after 20-40 minutes of recirculation. These values of neurotransmitters, however, were not different between aged and adult rats during ischemia and reperfusion. CONCLUSIONS: It is unlikely that a presynaptic mechanism is involved in age-related vulnerability in the striatum of hypertensive rats.

Aging↗

PubMed1993

[Determination of synephrine in Oriental pharmaceutical decoctions containing aurantii nobilis pericarpium by ion-pair high-performance liquid chromatography. II].

A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of synephrine in thirty three species of oriental pharmaceutical decoctions containing Aurantii Nobilis Pericarpium. An ODS column and a mixed solvent system of water, acetonitrile, sodium dodecyl sulfate and phosphoric acid as a mobile phase were used for the separation. Synephrine was eluted without interference of other coexisting components within 15 min.

Chromatography, High Pressure Liquid↗

PubMed1993

[Basic and clinical evaluation of EIA (pin immuno assay, PIA) kit for antithyroglobulin antibody (TGAb) and antimicrosomal (antiperoxidase) antibody (TMAb)].

Newly developed enzyme immunoassay kit (Pin Immuno Assay, PIA) for quantitative determination of serum antithyroglobulin antibody (TGAb) and antimicrosomal (-peroxidase) antibody (TMAb) was evaluated. The method utilizes the Sandwich ELISA principle with a unique micropin as solid phase coated with antigen. Reproducibilities assessed by intra- and interassay variation were less than 6.9% (CV) and 7.2% for TGAb or 4.2% and 6.0% for TMAb respectively. Changes in the first or second incubation time did not affect both TGAb and TMAb values. Upper normal limits obtained from 47 healthy subjects were 150 IU/ml for TGAb and 25 IU/ml for TMAb. Positive results in TGAb were obtained 60.0% in patients with Graves' disease and 80.0% in chronic thyroiditis and in TMAb 77.8% in Graves' disease and 66.7% in chronic thyroiditis. Patients with other autoimmune diseases such as SLE, RA were also found high incidence of positive results, 48.3% for TGAb and 65.0% for TMAb respectively. These results indicate that the nonradioisotopic assay technique for thyroid autoantibodies are useful in diagnosis of autoimmune diseases especially thyroid diseases.

Autoantibodies↗

PubMed1992

Antagonism of ceruletide, a cholecystokinin analog, to the neurochemical effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine and MK-801, on regional dopaminergic neurons in the rat brain.

In the present study, we investigated the effects of ceruletide (CL), a cholecystokinin analog, on the neurochemical response to non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine (PCP) and MK-801, of the dopaminergic neuron systems in the discrete regions of the rat brain. Systemically administered PCP (7.5 mg/kg, i.p.) or MK-801 (1.0 mg/kg, i.p.) produced significant increases in the tissue contents of dopamine metabolite, homovanillic acid (HVA), in the prefrontal cortex, the nucleus accumbens and the olfactory tubercle but not in the nucleus caudatus putamen after 60 min. The effects of NMDA receptor antagonists in the nucleus accumbens and the prefrontal cortex were partially antagonized by pretreatment with CL (80 and 400 micrograms/kg, i.p., at 60 min prior to the drugs). While CL alone decreased the dopaminergic metabolism only in the nigrostriatal pathways in naive rats, the present results indicated that CL also attenuates the activities of the meso-limbic and meso-cortical dopaminergic neuron systems when these are enhanced by either PCP or MK-801.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Inhibition of ischemia-induced dopamine release by omega-conotoxin, a calcium channel blocker, in the striatum of spontaneously hypertensive rats: in vivo brain dialysis study.

The effect of omega-conotoxin GVIA (CgTX), an N-and L-type voltage-sensitive calcium channel (VSCC) blocker, on the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum before and during transient cerebral ischemia in spontaneously hypertensive rats was studied using an in vivo brain dialysis technique. Continuous perfusion of CgTX in the striatum was started 20 min before ischemia and concentrations of dopamine and DOPAC in the dialysate were measured using HPLC with an electro-chemical detector. Before ischemia, both 10 and 100 microM CgTX significantly lowered the concentration of dopamine, to 49% of the basal values. DOPAC concentrations also decreased significantly, by 28 and 17%, respectively. Forebrain ischemia, produced by bilateral carotid artery occlusion, reduced striatal blood flow to less than 6% of the resting value in each group. During 20 min of ischemia, the vehicle group showed a marked increase in dopamine (175 times the basal concentration). In the 10 or 100 microM CgTX perfusion group, in contrast, dopamine release was significantly attenuated, to 38 or 29% of the vehicle group, respectively. DOPAC concentrations decreased during ischemia to 58% of the basal value in the vehicle group and 49% in both CgTX groups. These results indicate that the massive release of striatal dopamine during ischemia depends largely on the influx of extracellular calcium via CgTX-sensitive VSCCs.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Excitatory and inhibitory amino acid changes in ischemic brain regions in spontaneously hypertensive rats.

Excitatory (glutamate, aspartate) or inhibitory amino acids (gamma-aminobutyric acid: GABA, taurine) and glutamine contents were examined in acutely induced cerebral ischemia in spontaneously hypertensive rats. At 20 min ischemia most of these amino acids remained unchanged, but glutamine significantly decreased by 14% in the CA3 hippocampal subfield. At 60 min ischemia glutamate significantly decreased by 14% in the CA3, aspartate by 17-26% in the CA3, cingulate cortex, septum and striatum. In contrast, GABA significantly increased by 48-106% in the cortices (frontal, parietal and cingulate), striatum and nucleus accumbens, but insignificantly in hippocampal subfields. Likewise, taurine increased in the parietal cortex and nucleus accumbens. Glutamine showed heterogeneous changes (increase in the nucleus accumbens and decrease in the CA3). Amino acid levels change during ischemia, but their changes are varied in each area, implying that different reaction of amino acids may explain the selective vulnerability to cerebral ischemia.

Amino Acids↗

PubMed1991

Characterization of receptors for insulin-like growth factors in human brain.

The structural properties of receptors for insulin-like growth factors (IGFs) in human brain were studied. Brain membranes were incubated with 125I-IGF-I or II, cross-linked with disuccinimidyl suberate and subjected to electrophoresis under reducing conditions and autoradiography. Two proteins with apparent molecular weights of 120 and 220 kD were specifically labeled. The labeled proteins were immunoprecipitated with monoclonal antibody to type IIGF receptors, indicating that they represent alpha-subunit and its dimer of type IIGF receptor. The size of brain alpha-subunit was smaller than placental alpha-subunit (130 kD). Treatment with N-glycosidase F reduced the brain alpha-subunit from 120 to 95 kD and the placental alpha-subunit from 130 to 105 kD. Neuraminidase decreased the placental alpha-subunit from 130 to 125 kD, but it had no effect on the mobility of the brain alpha-subunit. Solubilized IGF-I receptors from placenta were retained by wheat germ agglutinin and concanavalin A columns, and eluted with the specific sugars. In contrast, solubilized IGF-I receptors from brain did not bind to these columns. These results indicate that human brains have only type IIGF receptors and that the molecular size of the alpha-subunit in brain receptors is smaller than in placental receptors. The size discrepancy may result from the differences in both protein and carbohydrate moieties.

Affinity Labels↗

PubMed1991

Age-related vulnerability to cerebral ischemia in spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: We sought to determine the effects of aging on regional cerebral blood flow and ischemic brain damage in transient cerebral ischemia in rats. METHODS: Five adult (5-6 months) and five aged (18-22 months) female spontaneously hypertensive rats were subjected to 20 minutes of bilateral carotid occlusion and 60 minutes of recirculation under amobarbital anesthesia (100 mg/kg i.p.). Regional cerebral blood flow in the hippocampus and striatum was measured using the hydrogen clearance method. Nine adult and 14 aged rats were subjected to 20 minutes of bilateral carotid occlusion or were sham-operated under ether anesthesia. Seven days after 20 minutes of cerebral ischemia, the rats' brains were perfusion fixed. Ischemic damage in the hippocampus and striatum was graded (0 [normal] to 3 [majority of neurons damaged]). RESULTS: After 20 minutes of bilateral carotid occlusion, striatal cerebral blood flow decreased to 9.1 +/- 1.5 and 3.9 +/- 2.0 ml/100 g/min in aged and adult rats, respectively, and hippocampal cerebral blood flow decreased to 8.6 +/- 2.4 and 5.7 +/- 2.4 in aged and adult rats, respectively. Although these ischemic cerebral blood flow values were not significantly different between the two age groups, scores for ischemic damage in the hippocampus CA-1 subfield and striatum were significantly higher in aged than in adult rats (p less than 0.05, Kruskal-Wallis' h test with Bonferroni correction). CONCLUSIONS: We conclude that aging may be a primary factor in the development of greater ischemic neuronal damage observed in aged hypertensive rats.

Aging↗