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Biomedical subjects

K Kiuchi

Publications and source records attributed to K Kiuchi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Long-term treatment with antipsychotic drugs in conventional doses prolonged QTc dispersion, but did not increase ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease.

OBJECTIVE: The aim of this study was to examine the hypothesis that long-term treatment with antipsychotic drugs in conventional doses prolongs QTc dispersion and increases ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease. METHODS: We measured QTc and QTc dispersion and ventricular tachyarrhythmias in 64 patients with schizophrenia, including 59 patients who received psychiatric medications, and five patients who did not receive psychiatric medications, and 45 healthy volunteers. None of the subjects had a history of cardiac disease or showed any abnormality in chest radiograph and transthoracic echocardiographic studies. None of the subjects had electrolyte abnormality. None of the subjects were taking drugs known to influence the QT interval, other than psychiatric medications. RESULTS: QTc and QTc dispersion were significantly (P < 0.017) increased in patients who received psychiatric medications compared with patients who did not receive psychiatric medications, or with healthy volunteers [QTc: 0.442 (0.029), 0.418 (0.029), 0.417 (0.028) s, QTc dispersion: 0.054 (0.013), 0.038 (0.017), 0.038 (0.009) s]. Daily ventricular premature beats were 183 (689), 77 (23), and 86 (149), respectively. No ventricular tachycardia was observed. There were no correlation between QTc and QTc dispersion and ventricular premature beats. CONCLUSION: Long-term treatment with antipsychotic drugs in conventional doses prolonged both QTc and QTc dispersion in patients with schizophrenia, but did not increase ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease. However, despite the negative findings, ventricular tachyarrhythmias may occur as a rare side-effect of antipsychotic drugs, particularly if a patient has additional risk factors.

Adult↗
PubMed1999

Changes in fecal microflora induced by intubation of mice with Bacillus subtilis (natto) spores are dependent upon dietary components.

We examined changes in mouse fecal microflora after various dietary components and Bacillus subtilis (natto) spores were delivered by intubation. The administration of intact spores of Bacillus subtilis (natto) did not affect fecal Enterobacteriaceae and Enterococcus spp. in all three diet groups; on the other hand, it did affect fecal Bacteroidaceae and Lactobacillus spp., depending upon the diets fed. The administration of autoclaved spores did not alter fecal microflora. In vitro cultures of Lactobacillus murinus obtained from mouse feces, together with Bacillus subtilis (natto) under aerobic conditions as a mixed culture, revealed that the growth of L. murinus was enhanced by the addition of intact spores of Bacillus subtilis (natto). This enhancement of growth was displayed only in media containing either sucrose, glucose, maltose, or fructose but not in media containing cornstarch, soluble starch, or microcrystalline cellulose. From these results it was evident that some metabolites of Bacillus subtilis (natto) produced during germination and (or) outgrowth of spores of this strain, requiring monosaccharides or oligosaccharides, participated in the enhancement of the growth of L. murinus.

Animals↗
PubMed1999

Left coronary artery-left ventricular fistula with acute myocardial infarction, representing the coronary steal phenomenon: a case report.

A 59-year-old man presented with a left anterior descending coronary artery to left ventricular fistula manifesting as myocardial infarction, representing the coronary steal phenomenon. Electrocardiography showed poor R progression in leads V1 through V3. The biochemical markers of myocardial injury were elevated. Creatine kinase level was 509 IU/l, creatine kinase MB isoenzyme (CK-MB)47 IU/l, cardiac troponin T 0.62 ng/ml, myosin light chain 6.1 ng/ml, and myoglobin 142 ng/ml. Thallium-201 myocardial perfusion imaging with dobutamine stress showed a dobutamine-induced perfusion deficit of the anteroseptal wall of the left ventricle with 0.1 mV ST-segment depression in II, III, aVF, V5, and V6. The mean left anterior descending blood flow measured with the Doppler guidewire was increased from 211 to 378 ml/min. Selective coronary arteriography showed dominant left coronary artery with the contrast medium streaming into the left ventricle via a maze of fine vessels from the distal left anterior descending coronary artery. No critical stenosis of the left anterior descending coronary artery was observed. Administration of acetylcholine 100 micrograms into the left coronary artery did not induce vasoconstriction of that artery. The fistula terminating in the left ventricle was ligated surgically and the patient became free of chest pain. Thallium-201 myocardial perfusion imaging with dobutamine stress revealed no perfusion deficit of the anteroseptal wall of the left ventricle. The presence of coronary steal phenomenon was detected by dobutamine stress myocardial imaging.

Coronary Vessel Anomalies↗
PubMed1998

Motor and learning dysfunction during postnatal development in mice defective in dopamine neuronal transmission.

Mice lacking expression of tyrosine hydroxylase (TH), the first and rate-limiting enzyme of the catecholamine biosynthetic pathway, in dopaminergic neuronal cell types were generated by a transgenic rescue approach to clarify the role of dopamine signaling during postnatal development. Introduction of the TH transgene directed by the dopamine beta-hydroxylase gene promoter into TH knockout mice restored noradrenaline and adrenaline synthesis, preventing perinatal lethality and cardiac dysfunction in the knockout mice. Lack of TH expression in the cells that normally express the dopaminergic phenotype resulted in a marked reduction of dopamine accumulation in the tissues, which led to multiple behavioral abnormalities at the juvenile stage. These abnormalities were characterized by a reduction in spontaneous locomotor activity, blockade of methamphetamine-induced hyperactivity, cataleptic behavior, and defects in active avoidance learning. In contrast, development of the pituitary gland as well as production and secretion of the pituitary peptide hormones dependent on hypothalamic dopaminergic control were normally maintained, despite defective dopamine synthesis. These results demonstrate that dopamine neurotransmission is essential for controlling spontaneous and voluntary movement and associative learning during postnatal development through the nigrostriatal and mesocorticolimbic pathways.

Animals↗
PubMed1998

Phosphorylation and activation of p70 S6 kinase by manganese in PC12 cells.

Previous study has shown that the treatment of PC12 cells with manganese, a MPTP-like neurotoxin, causes transcription-dependent apoptosis. This is a useful model system for the study of neuronal cell death. Manganese-induced apoptosis is accompanied by the induction of DNA fragmentation, expressions of c-Fos and c-Jun, and activation of the c-Jun N-terminal kinase U(JNK) pathway. Here, we report that manganese induces phosphorylation of p70 S6 kinase at Ser411 and Thr421/Ser424, and activates the enzyme. Thus, phosphorylation and activation of p70 S6 kinase are accompanied by transcription-dependent apoptosis, suggesting a role for p70 S6 kinase in this type of apoptosis.

Animals↗
PubMed1998

Dopamine D1-like receptor activation excites rat striatal large aspiny neurons in vitro.

The aim of this study was to elucidate electrophysiologically the actions of dopamine and SKF38393, a D1-like dopamine receptor agonist, on the membrane excitability of striatal large aspiny neurons (cholinergic interneurons). Whole-cell and perforated patch-clamp recordings were made of striatal cholinergic neurons in rat brain slice preparations. Bath application of dopamine (1-100 microM) evoked a depolarization/inward current with an increase, a decrease, or no change in membrane conductance in a dose-dependent manner. This effect was antagonized by SCH23390, a D1-like dopamine receptor antagonist. The current-voltage relationships of the dopamine-induced current determined in 23 cells suggested two conductances. In 10 cells the current reversed at -94 mV, approximately equal to the K+ equilibrium potential (EK); in three cells the I-V curves remained parallel, whereas in 10 cells the current reversed at -42 mV, which suggested an involvement of a cation permeable channel. Change in external K+ concentration shifted the reversal potential as expected for Ek in low Na+ solution. The current observed in 2 mM Ba2+-containing solution reversed at -28 mV. These actions of dopamine were mimicked by application of SKF38393 (1-50 microM) or forskolin (10 microM), an adenylyl cyclase activator, and were blocked by SCH23390 (10 microM) or SQ22536 (300 microM), an inhibitor of adenylyl cyclase. These data indicate, first, that dopamine depolarizes the striatal large aspiny neurons by a D1-mediated suppression of resting K+ conductance and an opening of a nonselective cation channel and, second, that both mechanisms are mediated by an adenylyl cyclase-dependent pathway.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Prevention of dopaminergic neuron death by adeno-associated virus vector-mediated GDNF gene transfer in rat mesencephalic cells in vitro.

Glial cell line-derived neurotrophic factor (GDNF) is known as a potent neurotrophic factor for dopaminergic neurons. Since adeno-associated virus (AAV) vector is a suitable vehicle for gene transfer into neurons, rat E14 mesencephalic cells were transduced with an AAV vector expressing GDNF. When compared with mock transduction, a larger number of dopaminergic neurons survived in AAV-GDNF-transduced cultures (234% and 325% of controls at 1 and 2 weeks, respectively; P < 0.01). Furthermore, the dopaminergic neurons in the latter cultures grew more prominent neurites than those in the former. These findings suggest that AAV vector-mediated GDNF gene transfer may prevent dopaminergic neuron death, and is therefore a logical approach for the treatment of Parkinson's disease.

Animals↗
PubMed1998

Molecular cloning and expression analysis of GFR alpha-3, a novel cDNA related to GDNFR alpha and NTNR alpha.

Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are structurally related to TGF-beta and are survival factors for sympathetic, sensory, and central nervous system neurons. GDNF transmits its signal primarily through a receptor complex containing the receptor tyrosine kinase Ret and a glycosyl-phosphatidylinositol (GPI)-linked receptor, GDNFR alpha. NTN utilizes a receptor complex system that consists of Ret and another GPI-linked receptor, NTNR alpha. We have identified a mouse cDNA, termed GFR alpha-3, that encodes a putative GPI-linked receptor. At the protein level, mouse GFR alpha-3 is 35% identical to mouse GDNFR alpha and 36% identical to mouse NTNR alpha. Northern blot analysis showed that GFR alpha-3 is expressed in fetal mouse heart, brain, lung, and kidney and adult heart. These results indicate that the tissue distribution of GFR alpha-3 mRNA is different from that of GDNFR alpha or NTNR alpha mRNA, and suggest that GFR alpha-3 may function in differentiation of embryonic cells expressing its mRNA.

Amino Acid Sequence↗
PubMed1998

Microglial NO induces delayed neuronal death following acute injury in the striatum.

We have established a novel injury model in the central nervous system by a stereotaxic injection of ethanol into rat striatum to induce necrosis. With this model, we clarify a function of inducible nitric oxide synthase (iNOS) in a healing mechanism around a necrotic lesion. A semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that the iNOS mRNA arose at 6 h, peaked at 24 h, and declined to a lower level 48 h after an intrastriatal 5-microL ethanol injection. From in situ hybridization, this iNOS mRNA was expressed in the area surrounding the injury. By immunohistochemistry, mononuclear cells at this boundary area of necrosis were stained with anti-iNOS antibody on the first day after the injury. These cells turned out to be reactive microglia from the positive staining of GSA-I-B4, ED-1 and OX-42. Haematoxylin-eosin (HE) staining showed that neurons in this boundary area gradually disappear up to 5 days after the injury with an increment of microglial cells, and this area became cavernous. Nuclei of neurons in this area were stained positive by the terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end-labelling (TUNEL) assay on the first day after the injury. These TUNEL-positive neurons gradually disappeared toward the third day, while microglial cells increased. L-Ng-nitro-arginine methylester (L-NAME), a competitive NOS inhibitor, administration diminished the elimination of neurons by microglia in this boundary area surrounding necrosis. Microglial NO may act as a neurotoxic agent to eliminate damaged neurons near the necrosis in the form of delayed neuronal death, and may reintegrate the neuronal circuits with functionally intact neurons.

Animals↗
PubMed1998

Dominant negative ATF1 blocks cyclic AMP-induced neurite outgrowth in PC12D cells.

Extension of the neuronal process is a crucial step for establishment of the neuronal network. As CREB preferentially forms heterodimers with ATF1 in PC12D cells, we examined the roles of the CREB/ATF1 heterodimer on cyclic AMP (cAMP)-induced neurite extension, using originally constructed ATF1RL, which has a point mutation at the DNA binding domain of ATF1. Transient expression of ATF1RL suppressed the protein kinase A/CREB-induced expression of the CRE reporter gene as expected. Treatment with forskolin elicited a relatively poor mRNA induction for immediate early genes in PC12D-ATF1 RL cells, a PC12D cell line stably expressing ATF1RL, in comparison with the parental PC12D cells. Furthermore, the PC12D-ATF1RL cells were proved to be defective at cAMP-induced neurite outgrowth. In contrast, both the gene expression and the differentiation after nerve growth factor treatment noted in PC12D-ATF1RL cells were at the same levels as those in the parental cells. These data provide us the first evidence that links CREB/ATF1 to the cAMP-induced differentiation of PC12 cells.

Activating Transcription Factor 1↗
PubMed1998

Activation of JNK pathway and induction of apoptosis by manganese in PC12 cells.

Manganese is known to induce neurological disorders similar to parkinsonisms. A dopamine deficiency has been demonstrated in Parkinson's disease and in chronic manganese poisoning, suggesting that the mechanisms underlying the neurotoxic effects of the metal ion are related to a functional abnormality of the extrapyramidal system. However, the details have yet to be elucidated. Here we report that manganese causes characteristic internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis, in PC12 cells. It was transcription dependent, relatively specific for manganese, and blocked in Bcl-2-overexpressed PC12 cells. The results indicate that apoptosis may play a role in the dopaminergic neurotoxicity associated with manganese, the first metal to be reported to induce this form of cell death. The early biochemical events show the impairment of energy metabolism, and the process may require new synthesis of proteins such as c-Fos and c-Jun. In addition, manganese induces phosphorylation of c-Jun at Ser63 and Ser73 and SEK1/MKK4 (c-Jun N-terminal kinase kinase) at Thr258 and tyrosine phosphorylation of several proteins. These results indicate that manganese activates specific signal cascades including the c-Jun N-terminal kinase pathway.

Animals↗
PubMed1998

Purulent pericarditis with tamponade caused by Salmonella enteritidis.

The incidence of purulent pericarditis has declined. However, mortality remains high. We describe a case of purulent pericarditis with tamponade caused by Salmonella enteritidis, and emphasize the importance of early recognition, prompt institution of appropriate antibiotic therapy, and early surgical drainage for survival.

Adult↗
PubMed1998

[Potential role of primary hypercoagulability and antiphospholipid antibody as a risk factor of acute pulmonary thromboembolism].

To examine whether primary hypercoagulable states, such as protein C and protein S deficiencies and antiphospholipid antibody, are associated with an increased risk, severity and recurrence of acute pulmonary thromboembolism, the blood levels of antithrombin III, protein C, protein S, lupus anticoagulant, anticardiolipin antibodies were measured in 23 patients with acute pulmonary thromboembolism, 7 men and 16 women (mean age +/- SD, 52 +/- 5 years), admitted to Nippon Medical School Hospital from January, 1990 through December, 1997. Four patients (17.4%) had protein C deficiency, one had protein S deficiency (4.3%), 10 had lupus anticoagulant (43.5%), and 2 had anticardiolipin antibodies (8.7%). Hemodynamic evaluation by Swan-Ganz catheter and venography of the lower extremity to detect deep venous thrombi were carried out in 20 and 21 patients, respectively. There were no differences between the patients with and without primary hypercoagulable states in age (52 +/- 14 vs 52 +/- 19 years), gender, or percentage of patients with deep venous thrombi in the lower extremity (91.7% vs 88.9%). Mean pulmonary arterial pressure (38 +/- 9 vs 26 +/- 4 mmHg, p < 0.05) and total pulmonary vascular resistance (10 +/- 5 vs 6 +/- 2 Wood unit, p < 0.1) were higher in the 13 patients with primary hypercoagulable states compared with the 10 patients without primary hypercoagulable states. Recurrence of pulmonary thromboembolism tended to be higher in the 13 patients with primary hypercoagulable states compared with the 10 patients without primary hypercoagulable states (46.2% vs 10.0%, p < 0.1). These findings suggest that primary hypercoagulable states, such as protein C and S deficiencies and antiphospholipid antibody, are associated with the severity and increased risk and recurrence of acute pulmonary thromboembolism.

Acute Disease↗
PubMed1997

Distribution of RGS4 mRNA in mouse brain shown by in situ hybridization.

RGS proteins (regulators of G protein signaling) are a newly identified group of proteins that negatively regulate G proteins. Some, including RGS4, have been shown to act as GTPase-activating proteins for several members of the Gi alpha subunits and the Gq alpha subunit. However, the signaling pathways of G protein-coupled receptors regulated by RGS4 are not well understood. We isolated the mouse RGS4 cDNA to investigate the roles of RGS4 protein in mouse brain. Expression of mouse RGS4 in yeast stimulated adaptation to mating pheromone, suggesting that it negatively regulates that G protein-mediated signaling pathway. Northern blot analysis of various mouse tissues revealed that RGS4 is expressed at high levels in brain, moderately low levels in heart, and very low levels in lung, liver, and skeletal muscle. In situ hybridization of mouse brain showed RGS4 mRNA mainly in the cerebral cortex, hippocampus, anterior olfactory nucleus, piriform cortex, olfactory tubercle, caudate-putamen, nucleus accumbens, islands of Calleja, substantia nigra, amygdala, the granular layer of cerebellum, middle cerebellar peduncle, and perifacial zone. These results suggest that RGS4 is expressed in various types of cells in the brain and may regulate multiple G protein-mediated signaling pathways.

Animals↗
PubMed1997

Cloning and structural organization of the gene encoding the mouse glial cell line-derived neurotrophic factor, GDNF.

cDNA for glial cell line-derived neurotrophic factor (GDNF) was cloned from mouse neonatal brain by the method of 5'-rapid amplification of cDNA end (5'-RACE), and the sequence of it's 5'-untranslated region (5'-UTR) was determined. The mouse GDNF gene was then isolated from a genomic library and analyzed for its nucleotide sequence. In vitro translation analysis indicated that the second ATG codon in an open reading frame is the translation start point. Structural analysis of the isolated clones showed that the GDNF gene was separated into three exons and the actual translation start point was present in the second exon. RNA blot hybridization analysis indicated that the GDNF mRNA is approximately 4.5 kb long. The transcriptional start site in the GDNF gene was determined and a typical TATA box sequence was found in the promoter region. On the other hand, the gene expression of GDNF in C6 glioma cells was transiently induced by treatment with phorbol myristate acetate (PMA), but not by forskolin.

Amino Acid Sequence↗
PubMed1997

In vitro and in vivo expression of inducible nitric oxide synthase during experimental endotoxemia: involvement of other cytokines.

In this study, we investigated the expression of genes for inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) of Kupffer cells in the presence of lipopolysaccharide (LPS), and the tissue expression of iNOS in a rat liver after LPS injection at various time intervals. The effects of L-NG-nitroarginine-methyl-esther HCI (L-NAME), a NO inhibitor, also were examined. The mRNA transcripts of TNF-alpha, IL-1 beta, and IL-6 were rapidly detected no more than at 1 h after LPS stimulation, whereas the iNOS transcript was detectable from 3 h after LPS stimulation and maximally increased at 12 h. This fact suggested that these early induced cytokines were related to expression of iNOS. Using an anti-iNOS antiserum raised against recombinant iNOS protein, immunohistochemical analysis was made to reveal kinetics of NO producing cells. The cells immunoreactive for iNOS appeared at 6 h post-LPS injection in the sinusoids of the liver. By structural and immunohistochemical studies, almost all iNOS positive cells were identified as Kupffer cells and endothelial cells. The number of cells immunoreactive for iNOS increased until 12 h post-LPS injection. At 24 h after LPS injection, iNOS positive cells were restricted to the foci of spotty necrosis. Hepatic injury measured by released enzymes was increased by pretreatment of L-NAME before LPS injection.

Animals↗
PubMed1997

Value of cardiac ultrafast computed tomography for detecting right atrial thrombi in chronic atrial fibrillation.

We evaluated the accuracy of cardiac ultrafast computed tomography in diagnosing atrial thrombi in 70 patients with chronic atrial fibrillation, and identified the predictors of atrial thrombi from among clinical, echocardiographic, and ultrafast computed tomographic features. Ultrafast computed tomography identified 11 atrial thrombi in 9 patients: 4 patients had thrombi in the left atrium, 3 in the right, and 2 in both. Transthoracic echocardiography detected only 4 left atrial thrombi, and enlargement of the left or right atrium was associated with atrial thrombi (p <0.05).

Aged↗