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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 397 records · Page 22Linked to original sources

Acutely administered haloperidol has little effect on steady-state visual evoked potentials from pattern-reversal stimulations in treated schizophrenics.

The amplitude changes in steady-state visual evoked potentials (VEPs) from pattern-reversal stimulations at 30 min after an intramuscular injection of haloperidol were examined in 10 treated schizophrenics. The VEP amplitudes to hemi-field or full-field pattern-reversal stimulations with a standard check size were almost unchanged after the haloperidol injection as compared with those before the injection. However, while the VEP amplitudes to the full-field stimulations were significantly higher in the midline occipital portion than in the right occipital portion before the injection, no significant difference was observed after the injection. Further, the VEPs similarly responded to the change in the check sizes used in the full-field stimulations before and after the injection, both showing significantly lower amplitudes only at the large check size of 4.1 degrees in a visual angle than that of 1.0 degrees. These results indicate that acutely administered haloperidol has little effect on steady-state VEPs from pattern-reversal stimulations in treated schizophrenics.

Adult↗

Time course of dopamine-D2 and serotonin-5-HT2 receptor occupancy rates by haloperidol and clozapine in vivo.

In vivo occupancy of dopamine-D1, D2 and serotonin-5-HT2 receptors by haloperidol 10 mg/kg and clozapine 20 mg/kg were studied. Rats were injected intravenously with [3H]-YM-09151-2, [3H]-SCH23390, or [3H]-ketanserin 10 min after the administration of the tested drugs. Fifteen to 240 min after the ligand injection, the receptor occupancy rates of the drugs in the striatum and frontal cortex were calculated. Clozapine demonstrated the higher 5-HT2 and lower D2 occupancies in the respective regions. A dose-response analysis of D2 and 5-HT2 receptor occupancy by the drugs consolidated the higher 5-HT2 binding affinity of clozapine in comparison with haloperidol. The present methodology may serve as an accurate tool to evaluate the peculiarity of various antipsychotics.

Animals↗

Protective effects of bradykinin on the ischaemic heart: implication of the B1 receptor.

1. We studied the role of bradykinin (BK) and its active metabolite Des-Arg9-BK on noradrenaline release in association with the incidence of ventricular arrhythmias at reperfusion of the ischaemic myocardium. 2. Experiments were performed in Langendorff perfused isolated hearts of rats subjected to 30 min no flow followed by 5 min reperfusion. The electrocardiogram was monitored continuously and noradrenaline was measured in the effluent as well as in the myocardial tissue. 3. In untreated hearts, cumulative noradrenaline overflow following global ischaemia reached 226 +/- 35 pmol g-1 of heart (n = 8, P < 0.05) during the 5 min of reperfusion along with ventricular tachycardia and/or fibrillation. A decrease in myocardial noradrenaline (-31%) was also observed. 4. Bradykinin perfused at concentrations between 0.01 and 1 microM, 10 min before flow was stopped and at reperfusion, inhibited noradrenaline overflow in a concentration-dependent manner. At a concentration of 1 microM, bradykinin completely abolished noradrenaline overflow. For the same concentration of bradykinin, myocardial noradrenaline contents were significantly higher (n = 5-8, P < 0.05). Ventricular fibrillation but not ventricular tachycardia was also prevented. 5. Des-Arg9-BK (0.1 microM) in the same experimental conditions had similar effects. While Hoe 140, a selective antagonist at B2 receptors, did not abolish the effects of bradykinin, Lys [Leu8] Des-Arg9-BK, an antagonist at B1 receptors, abolished the effects of both Des-Arg9-BK and bradykinin. 6. These results suggest that the cardioprotective action of bradykinin in the preparation may be mediated partially by an inhibitory effect on noradrenaline liberation which could be mediated by the activation of B1 receptors.

Animals↗

Delirium associated with Joseph disease.

Three Japanese patients with Joseph disease from different families developed sleep disturbance, followed by delirium at the middle to end stage. Brain CT scans of the three patients showed brainstem tegmental atrophy. EEG revealed slowing of background activity. Two necropsy cases showed degeneration of the reticular formation, raphe nuclei and locus ceruleus in the brainstem tegmentum in addition to the common pathological findings of Joseph disease. The clinicopathological correlation between the delirium and the brainstem tegmental atrophy in Joseph disease is discussed.

Atrophy↗

Effects of nifedipine and Bay K 8644 on stimulation-induced adrenal catecholamine secretion in the dog.

The effects of nifedipine and BAY K 8644 on the adrenal medullary secretion in response to direct splanchnic nerve stimulation were studied in anesthetized dogs. Supramaximal stimulation (12 V) was given on the left splanchnic nerve at a frequency of 2 Hz with three different pulse durations (0.2, 2, and 20 ms) for a total period of 1.5 min. Each stimulation was given for 30 s without interruption between each stimulation. Plasma concentrations of epinephrine and norepinephrine were measured in adrenal venous and aortic blood. In the vehicle control group, epinephrine and norepinephrine concentrations in adrenal venous blood proportionally increased with the lengthening of the pulse duration without significant changes in catecholamine concentrations in aortic blood. In dogs receiving nifedipine (100 micrograms/kg iv), the net increase in adrenal venous epinephrine concentration during stimulation with 20-ms pulse duration was attenuated by approximately 50% (P < 0.05). In dogs treated with BAY K 8644 (30 micrograms.kg-1.min-1 iv), both adrenal venous epinephrine and norepinephrine secretions evoked by stimulation with 20-ms pulse duration were significantly enhanced by approximately 50%. The present results suggest that the secretion of adrenal catecholamines under in vivo conditions is controlled through mechanism(s) involving dihydropyridine sensitive L-type Ca2+ channels presumably localized on the surface of adrenal medullary chromaffin cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

In vivo evidence for adrenal catecholamine release mediated by nonnicotinic mechanism: local medullary effect of VIP.

The aim of the present study was 1) to develop a model in anesthetized dogs in which local infusion of a given substance could be made to the adrenal gland without any systemic effects and 2) to show in this model the potential existence of a nonnicotinic mechanism involved in adrenal catecholamine secretion. Plasma catecholamine concentrations were determined by an high-performance liquid chromatography method. The local infusion into the left adrenolumbar artery (0.5 ml/min for 1 min) of either dimethylphenylpiperazinium (0.3-3.0 micrograms/ml) or vasoactive intestinal peptide (0.1-10.0 micrograms/ml) resulted in dose-dependent increases in both epinephrine and norepinephrine secretions. Neither aortic pressure nor plasma catecholamine levels altered during the drug infusion. The net increases in adrenal catecholamine secretion obtained with dimethylphenylpiperazinium were abolished by the nicotinic blockade with pentolinium (2 mg/ml, 0.5 ml/min for 2 min). However, the net catecholamine responses to vasoactive intestinal peptide remained unaffected in the presence of the same dose of pentolinium. The results suggest that there exists a nonnicotinic mechanism that may be implicated in the local regulation of medullary catecholamine secretion in the dog adrenal gland. This model may be a useful tool for studying local physiological role(s) of various neurotransmitters and neuromodulators in the adrenal secretory function in vivo.

Adrenal Glands↗

Diffuse cerebral hypoperfusion in epileptic patients observed from quantitative assessment with single photon emission computed tomography using N-isopropyl-(iodine-123)-p-iodoamphetamine.

Quantitative assessment of regional cerebral blood flow (rCBF) in the bilateral cerebral and cerebellar cortices was performed in 15 epileptic adult patients receiving chronic high-dose antiepileptic drug therapy and 22 normal volunteers matched for sex and age, using single photon emission computed tomography with N-isopropyl-(iodine-123)-p-iodoamphetamine. The entire averaged rCBF value in the epileptic patients, i.e. 52.8 +/- 13.7 ml/10 g/min (range: 25-78 ml/100 g/min), was significantly lower as compared with that in the normal subjects, i.e. 69.1 +/- 14.2 ml/100 g/min (range: 46-102 ml/100 g/min). Six of the 15 patients showed absolute rCBF values less than the minimum of the normal range, i.e. 46 ml/100 g/min, in all or most of the measured brain tissues. There was a significant correlation between the diffuse cerebral hypoperfusion and simultaneous ingestion of phenytoin and phenobarbital. The possible effects of antiepileptic drugs on rCBF are discussed.

Adult↗

Probable cerebellar abnormality on N-isopropyl-(iodine-123)-p-iodoamphetamine single photon emission computed tomography scans in an epileptic patient receiving long-term high-dose phenytoin therapy.

Quantitative assessment of regional cerebral blood flow (rCBF) was performed in a 22-year-old man with intractable temporal lobe epilepsy on long-term high-dose phenytoin (PHT) therapy, using single photon emission computed tomography (SPECT) with N-isopropyl-(iodine-123)-p-iodoamphetamine. In all the SPECT scans repeated three times with changes in the PHT dose, absolute rCBF values were lower in most of the cerebral and cerebellar regions measured, as compared with 5 normal subjects matched for sex and age, and 22 normal subjects including the 5 men. Both the cerebellar to frontal rCBF ratio and cerebellar to cerebral rCBF ratio in the patient persistently showed low values, probably reflecting abnormal relative cerebellar hypoperfusion, whereas X-ray computed tomography and magnetic resonance brain imaging showed no abnormal findings. However, this probable cerebellar abnormality on SPECT was to some degree reversible with decreases in the PHT dose. These results suggest the utility of SPECT scans for early detection of cerebellar abnormalities known to be often present in epileptic patients, and imply a risk of long-term high-dose PHT therapy.

Adult↗

123I-IMP SPECT brain imaging in epileptic psychosis: a study of two cases of temporal lobe epilepsy with schizophrenia-like syndrome.

To examine the relationship between functional abnormality of the brain and the development of epileptic psychosis, regional cerebral blood flow (rCBF) patterns with single photon emission computed tomography (SPECT) using N-isopropyl-(iodine-123)-p-iodoamphetamine (123I-IMP) were serially examined in interictal stages with and without the psychotic state in 2 medicated patients with temporal lobe epilepsy with schizophrenia-like syndrome. Both patients had epileptic EEG foci in the left temporal lobe and schizophrenia-like syndrome in Bruens' classification of epileptic psychosis, mainly consisting of auditory hallucinations and delusions of persecution and reference accompanying the enhancement of interictal epileptic discharges. In both patients, the SPECT scans obtained in the stages without the psychotic state revealed focal hypoperfusion images in the left temporal lobe regionally consistent with the EEG foci. On the other hand, the SPECT scans in the stages with the psychotic states revealed focal hyperperfusion images in the left temporal lobe or amygdala in case 1, and a normal perfusion pattern without asymmetric images of the right and left temporal lobes in case 2. These results suggest that temporo-limbic dysfunction, in particular hyperfunction in the temporo-limbic system in the left dominant hemisphere, arises at the time of the psychotic state in epileptic psychosis.

Adult↗

Suppression of gene expression of myeloperoxidase (MPO) by gamma-interferon (IFN-gamma) in HL60 cells.

The gene expression of myeloperoxidase (MPO) in HL60 cells, as tested by Northern blot analysis with a MPO gene probe, was markedly suppressed at 9 h after the addition of gamma-interferon (IFN-gamma) (200 U/ml), whereas cytochemically detected MPO activity, cell surface antigen expression, and cell morphology remained unchanged even at 48 h. IFN-gamma of 50 U/ml was sufficient for the suppression at 24 h. When the HL60 cells treated with IFN-gamma (200 U/ml) for 24 h were cultured in the absence of IFN-gamma for another 24 h, the transcript of MPO gene reverted to a level comparable to that of the HL60 cells cultured thoroughly in the absence of IFN-gamma, indicating the reversibility of the suppression. The suppression of MPO expression at RNA level, probably independent of differentiation, is a biological activity exerted by IFN-gamma, which has not been previously reported.

Cell Line↗

[Cytokine in phenotypic analysis of leukemia/lymphoma: suppression of gene expression of myeloperoxidase by IFN-gamma and subset of AML M1 defined by CD45RO+/RA-, CD7(-), CD34(-) and non-inducible HLA-DR antigen].

One of 8 to 12 pre-B ALL cells co-express CD13 and CD33 antigens, but such blasts do not express myeloperoxidase (MPO) even on electronmicroscopy or mRNA. MPO+ pre-B ALL is extremely rare (1/50-1/100), however a cell-line (Tahr87) was established in culture. In contrast, T-lineage blasts express CD13/33 antigens regularly in the pro-thymic stage (CD7+ 5+ 2+ 3- 4- 8- or more immature), and a limited expression of MPO is rather commonly detected particularly in recurrences. The co-expression of CD3 epsilon/MPO or CD3 epsilon/delta/MPO mRNA has been demonstrated. Thus, the regulation of MPO expression is of utmost importance in interpreting the phenotypes of leukemia/lymphoma. While testing the effects of several cytokines on MPO expression, IFN-gamma was found to suppress the gene expression of MPO in HL60 cells. This suppression was not accompanied by differentiation, termination of proliferation or reduction of cytochemical MPO+ cells, and was reversible. Among 22 cases of M1 AML blasts, 8 cases were HLA-DR(-). DR antigen was induced by the presence of a mixture of IFN-gamma, TNF-alpha and TPA in 4 cases, but not in the other 4 cases. The blasts of the latter 4 cases were always CD34(-), CD7(-) and CD45RA-/RO+, and constituted a distinct M1 subset which has not previously been reported.

Antigens, CD↗

[Maternal and cord blood thyroid hormones in Graves' disease and fetal states].

Serum concentrations of thyroid hormones (T3, T4, fT3 and fT4), TSH and TRAb in 14 mothers with Graves' disease at 1-4 weeks before delivery were comparably studied with cord blood hormone levels and various fetal states. Twelve mothers were on anti-thyroid drugs and 2 were drug-free, with 8 being euthyroid and 6 being hyperthyroid. Serum concentrations of T3, T4 and fT3 in cord blood were all the same regardless of maternal thyroidal function. Though cord blood TRAb levels correlated with maternal levels, cord fT4 levels were low in those who given antithyroid drugs. TSH levels in cord blood were low in Cesarean section delivery and babies with low birth weight. Birth weight and gestational weeks were both inversely correlated with maternal T4, fT4, fT3 and TRAb concentrations. Thus, maternal hormone levels at late stage of pregnancy in Graves' disease could be useful indices for perinatal risk.

Adult↗

Major histocompatibility complex restriction of maternally induced suppression in young adult mice.

This study focused on the mode in which maternal T cells induce suppression of plaque-forming cell (PFC) response in offspring. The maternal T cells of C57BL/6J pregnant mice, which had been intraperitoneally injected with 2 x 10(8) of sheep red blood cells (SRBC) on day 12 of gestation, were transferred, 5 days after immunization, into (C3H/HeJ x C57BL/6J)F1 normal pregnant mice on day 12 of gestation. The (C3H/HeJ x C57BL/6J)F1 x C3H/HeJ offspring of (C3H/HeJ x C57BL/6J)F1 recipient pregnant mice were reared to more than 6 weeks of age, and their anti-SRBC PFC responses were examined. Suppression of anti-SRBC PFC response was observed in H-2bxk but not H-2k offspring. Thus, maternal T cells of SRBC-immunized pregnant mice induce suppression of anti-SRBC PFC in offspring with restriction to major histocompatibility complex (MHC) haplotype utilized in maternal T-cell responses during pregnancy. Maternal CD4+ T cells are responsible for the MHC-restricted induction of PFC suppression in offspring. Furthermore we demonstrated, in this report, using adoptive transfer of maternal T cells from SRBC-immunized pregnant mice and in vitro secondary PFC assay in the offspring, that maternal T-cell-mediated suppression results from the development of CD4+ suppressor T cells in offspring. Moreover, the activation of suppressor T cells in offspring depends on the recognition of SRBC antigens presented in association with the same MHC haplotype as that utilized in the maternal T-cell response during pregnancy. Thus, the maternal T cells of SRBC-immunized pregnant mice generate a repertoire of suppressor T cells in their offspring.

Animals↗

Efficacy of sulthiame (Ospolot) on motor partial seizure status during sleep in a patient with motor cortex epilepsy.

An 18-year-old female patient with a particular form of intractable motor cortex epilepsy, in which motor partial seizure status occurred only during sleep every night, was reported focusing on the drastic efficacy of sulthiame on the seizure status. Moreover, the present study demonstrated that single photon emission computed tomography (SPECT) and pulse oximetry examinations, both of which were performed in the ictal state, were useful for the regional diagnosis of the epileptic focus and observations of the seizure frequency, respectively. The therapeutic effect, epileptic picture and clinical examinations described here appear to be relatively rare in the literature, and therefore, this case report may be of clinical significance.

Adult↗

Deletion mapping of chromosome 3p in human uterine cervical cancer.

Deletion mapping of chromosome 3p was performed on 47 cases of human uterine cervical cancer using 24 polymorphic DNA markers including five inter-Alu DNA markers and two NotI-boundary cosmid markers obtained in our laboratory. The most likely order of these 24 polymorphic DNA markers was determined as being cen-[D3S4, H8]-D3S693-D3S659-D3S30-D3S687-[D3S2, UR9, UR47]-J36-J17-GNAI2B-D3F15S2-D3S643- D3S32-D3S23-D3S686-H35-UR189-D3S685-D3S 11 - D3S12-THRB-D3S22-pter, based on the data from radiation hybrid mapping genetic linkage analysis and in situ hybridization. Loss of heterozygosity (LOH) at one or more loci on chromosome 3p was detected in 21 of 47 cases (45%). Four tumors showed partial or interstitial deletions, and the common region of LOH in these tumors was 3p13-p21.1 between the D3S30 marker and the D3S2 marker. Candidates for tumor-suppressor genes, APEH, D8, GNA12B, ZNF35, RARB, THRB and RAFI, were all mapped outside of the common region in uterine cervical cancer. However, this region is commonly deleted in carcinoma of the lung, breast and kidney, and encompasses the breakpoint of the (3;8) translocation in hereditary renal cell carcinoma. This result indicates the presence of a novel tumor-suppressor gene in the region of 3p13-p21.1, which is involved in the development of several human cancers.

Base Sequence↗

[Histidine-rich glycoprotein in diabetics].

Histidine-rich glycoprotein (HRGP) has been believed to have anti-fibrinolytic activity through its binding to plasminogen. Diabetic complications such as retinopathy or nephropathy are considered to be related to impaired coagulation-fibrinolysis system. Therefore, we studied the serum levels of HRGP in diabetics. There were no significant alterations of serum HRGP levels in comparison with normal controls, nor was there a mutual relation between HRGP levels and HbA1 values. Moreover, the molecular weight of HRGP was not deviated from control. These results suggest that HRGP might not have critical role on fibrinolytic system in diabetics.

Adult↗