Biomedical subjects

T Hori

Publications and source records attributed to T Hori.

At least 145 records · Page 8Linked to original sources

PubMed2000

Morphological evidence for neural interactions between leptin and orexin in the hypothalamus.

Both leptin and orexin have been recently discovered as peptides involved in feeding regulation. The morphological evidence of neural interaction between leptin and orexin, one considered to inhibit food intake and the other to stimulate it in the central nervous system (CNS), was studied by use of double immunostaining method. The leptin receptor-like immunoreactive (LR-LI) neurons in the hypothalamic arcuate nucleus and ventromedial nucleus were innervated by orexin-like immunoreactive (OX-LI) neurons. The distribution of LR-LI neurons in the hypothalamus was very similar to that of OX-LI neurons. These results may suggest that leptin and orexin are intimately correlated with each other and that they reciprocally regulate feeding at the hypothalamic level.

Animals↗

PubMed2000

Crystal structure of rhodopsin: A G protein-coupled receptor.

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural features, including a bundle of seven transmembrane alpha helices connected by six loops of varying lengths. We determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution. The highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the seven-helix transmembrane motif. The ground-state chromophore, 11-cis-retinal, holds the transmembrane region of the protein in the inactive conformation. Interactions of the chromophore with a cluster of key residues determine the wavelength of the maximum absorption. Changes in these interactions among rhodopsins facilitate color discrimination. Identification of a set of residues that mediate interactions between the transmembrane helices and the cytoplasmic surface, where G-protein activation occurs, also suggests a possible structural change upon photoactivation.

Amino Acid Motifs↗

PubMed2000

The role of GTP-binding protein activity in fast central synaptic transmission.

Guanosine 5'-triphosphate (GTP)-binding proteins (G proteins) are involved in exocytosis, endocytosis, and recycling of vesicles in yeast and mammalian secretory cells. However, little is known about their contribution to fast synaptic transmission. We loaded guanine nucleotide analogs directly into a giant nerve terminal in rat brainstem slices. Inhibition of G-protein activity had no effect on basal synaptic transmission, but augmented synaptic depression and significantly slowed recovery from depression. A nonhydrolyzable GTP analog blocked recovery of transmission from activity-dependent depression. Neither effect was accompanied by a change in presynaptic calcium currents. Thus, G proteins contribute to fast synaptic transmission by refilling synaptic vesicles depleted after massive exocytosis.

Action Potentials↗

PubMed2000

Molecular cloning of a novel human protein kinase, kpm, that is homologous to warts/lats, a Drosophila tumor suppressor.

A novel human protein kinase, designated kpm, was identified and molecularly cloned. The isolated cDNA clone had an open reading frame consisting of 1088 amino acid residues with a putative kinase domain located near the carboxy-terminus. Homology search revealed that kpm belongs to a subfamily of serine/threonine protein kinases including warts/lats, a Drosophila tumor suppressor. Among these, kpm is most homologous to, but distinct from, recently reported LATS1, a human homolog of Drosophila warts/lats. Northern blot analysis disclosed that kpm is expressed as a 6.0 kb transcript in most of the tissues examined and also as an additional shorter 4.0 kb transcript in testis. Western blotting using polyclonal rabbit anti-kpm antibody detected kpm protein as a band with an apparent Mr of 150 kD. Immune complex kinase assay of HA-tagged kpm showed that kpm had kinase activity and phosphorylated itself in vitro. Studies with synchronized HeLa cells indicated that kpm protein was expressed relatively constantly throughout the cell cycle and underwent significant phosphorylation at mitotic phase. These results suggest that kpm plays a role in cell cycle progression during mitosis and its deletion or dysfunction might be involved in certain types of human cancers.

Amino Acid Sequence↗

PubMed2000

Both amino- and carboxyl-terminal domains of TRAF3 negatively regulate NF-kappaB activation induced by OX40 signaling.

OX40 is a member of the tumor necrosis factor receptor (TNF-R) superfamily. We observed that overexpression of OX40 activated NF-kappaB, which was inhibited by dominant negative forms of TRAF2, NF-kappaB-inducing kinase (NIK), and IkappaB kinase (IKK) alpha. This indicates that OX40 signaling leads to NF-kappaB activation through the same cascade as TNF-R2. We then investigated the negative regulatory function of TRAF3 on OX40-induced NF-kappaB activation. TRAF3 blocked OX40-, TRAF2-induced NF-kappaB activation, but not NIK- and IKKalpha-induced NF-kappaB activation, indicating that TRAF3 blocks the pathway between TRAF2 and NIK. C-terminal deletion mutants as well as the N-terminal deletion mutant of TRAF3 inhibited NF-kappaB activation induced by OX40 or TRAF2. Since TRAF3 bound to OX40 through the C-terminal TRAF domain, the C-terminal domain is likely to work as a dominant negative mutant to compete the recruitment of TRAF2 to the receptor, which transmits the signal from OX40 to the downstream, NIK kinase. On the other hand, the N-terminal domain of TRAF3 seems to affect the downstream of TRAF2 binding. Thus, it is suggested that TRAF3 actively inhibits NF-kappaB activation induced by OX40.

Binding Sites↗

PubMed2000

Effects of repeated phencyclidine treatment on serotonin transporter in rat brain.

Phencyclidine (PCP) is known to be an inhibitor of serotonin (5-HT) uptake and to increase serotonergic activity. The development of tolerance to serotonergic stereotyped behaviors induced by repeated PCP treatment and changes of 5-HT transporters were examined. Backpedalling was significantly reduced in frequency following 14 days PCP treatment (7.5 mg/kg per day). Furthermore, repeated PCP treatment decreased the equilibrium dissociation constant (Kd) of [3H]paroxetine binding to 5-HT transporters in whole brain excluding the cerebellum without any change of maximum number of binding sites (Bmax). Single treatment with PCP failed to change binding parameters. These results indicate that repeated PCP treatment causes tolerance in serotonergic stereotyped behavior and increases affinity of 5-HT transporters for [3H]paroxetine binding. The increased affinity of 5-HT transporters could represent compensatory responses to chronic inhibition of 5-HT uptake by PCP.

Analysis of Variance↗

PubMed2000

Mechanism in progressive lacunar infarction: a case report with magnetic resonance imaging.

BACKGROUND: The mechanism of a progressive lacunar infarction is not well understood, and changes in ischemic tissue after onset have not yet been clarified clinically. OBJECTIVE: To investigate the pathophysiological characteristics of a case of progressive lacunar infarction using diffusion-weighted and conventional magnetic resonance imaging (MRI) scans. PATIENT: A 73-year-old woman was hospitalized 18 hours after stroke onset and was diagnosed as having a lacunar infarction in the perforating territory of the left middle cerebral artery. Despite treatment, the hemiparesis worsened, with the peak on the fourth day after onset. Diffusion-weighted and conventional MRI scans provided clues to the pathogenesis. FINDINGS AND CONCLUSIONS: In the acute stage, gradual enlargement of the hyperintense lesion, reflecting fresh ischemic tissue, and neurological deterioration were observed by serial examination of diffusion-weighted MRI scans. A conventional coronal MRI scan revealed a 2-layered ischemic lesion, suggesting the involvement of perforating arteries. These findings indicated that hemodynamic impairment of the microcirculation in the perforators was the major cause of the lacunar infarction.

Aged↗

PubMed2000

Association between favorable neuroblastoma and high expression of the novel metalloproteinase gene, nbla3145/XCE, cloned by differential screening of the full-length-enriched oligo-capping neuroblastoma cDNA libraries.

BACKGROUND: The biology of neuroblastoma (NBL) is at least partly regulated by neurotrophic factors and their receptors. PROCEDURE: To identify novel NBL-related genes that affect growth, differentiation, and programmed cell death of the tumor, we constructed full-length-enriched cDNA libraries by oligo-capping method. RESULTS: Semi-quantitative and quantitative real-time RT-PCR showed that the nbla3145 gene was significantly highly expressed in favorable subset of NBL. The nucleo-tide sequence of nbla3145 revealed that it was a novel member of metalloproteinase, endothelin-converting enzyme, and was the same gene recently reported as XCE. We also cloned nbla3145beta which was a novel truncated form of nbla3145 (or nbla3145alpha). CONCLUSIONS: Our results suggested that nbla3145/XCE plays an important role in regulating growth and differentiation of NBL.

Gene Expression Regulation, Neoplastic↗

PubMed2000

Differential expression of GABA(A) receptor subunit mRNAs and ligand binding sites in rat brain following phencyclidine administration.

Recent biochemical observations have suggested the abnormalities in the gamma-amino-butyric acid (GABA)ergic system in schizophrenic brains. In the present study, we investigated the subunits gene expressions and ligand binding of the GABA(A) receptor following acute and chronic administration of phencyclidine (PCP), which induces schizophrenia-like symptoms, in rats using in situ hybridization and in vitro quantitative autoradiography. PCP i.p. administration at a daily dose of 7.5 mg/kg resulted in a significant decrease in expression of alpha 1 subunit mRNA in cerebral cortices (cingulate (-13%) and temporal cortex (-6%)) and hippocampal formation (CA1 (-11%), CA2 (-10%), CA3 (-11%) and dentate gyrus (-12%)) 1 h after a single treatment. In the repeated PCP administrations for 14 days, the expression of beta 2 mRNA in the cerebellum (-10%) and of beta 3 mRNA in the cerebral cortices (cingulate (-12%), parietal (-16%) and temporal cortex (-16%), caudate putamen (-18%), inferior colliculus (-18%), and cerebellum (-15%) were significantly decreased. In addition, [(35)S]t-butylbicyclophosphorothionate (TBPS) binding was also reduced in layer IV of the frontoparietal cortex (-14%), inferior colliculus (-17%), and cerebellum (-12%) following chronic PCP treatment, while no changes were observed following acute PCP treatment. These results indicate that single and repeated administrations of PCP independently regulate the expression of GABA(A)/benzodiazepine (BZD) receptor subunits mRNA and its receptor binding in the brain.

Animals↗

PubMed2000

Effects of cocaine administration on receptor binding and subunits mRNA of GABA(A)-benzodiazepine receptor complexes.

The effects of intermittent intraperitoneal (i.p.) administration of cocaine (20 mg/kg) on GABA(A)-benzodiazepine (BZD) receptors labeled by t-[(35)S]butylbicyclophosphorothionate (TBPS), and on several types of mRNA subunits were investigated in rat brain by in vitro quantitative receptor autoradiography and in situ hybridization. Phosphor screen imaging with high sensitivity and a wide linear range of response was utilized for imaging analysis. There was a significant decrease in the level of alpha 1, alpha 6, beta 2, beta 3, and gamma 2 subunits mRNA, with no alteration of [(35)S]TBPS binding in any regions in the brain of rats at 1 h following a single injection of cocaine. In chronically treated animals, the mean scores of stereotyped behavior were increased with the number of injections. The level of beta 3 subunit mRNA was decreased in the cortices and caudate putamen, at 24 h after a final injection of chronic administrations for 14 days. In the withdrawal from cocaine, the frontal cortex and hippocampal complexes showed a significant increase in [(35)S]TBPS binding and alpha1 and beta 3 subunit mRNA in the rats 1 week after a cessation of chronic administration of cocaine. These findings suggest that the disruption of GABA(A)-BZD receptor formation is closely involved in the development of cocaine-related behavioral disturbances. Further studies on the physiological functions on GABA(A)-BZD receptor complex will be necessary for an explanation of the precise mechanisms underlying the acute effects, development of hypersensitization, and withdrawal state of cocaine.

Animals↗

PubMed2000

Milder childhood form of very long-chain acyl-CoA dehydrogenase deficiency in a 6-year-old Japanese boy.

UNLABELLED: We investigated the clinical and biochemical characteristics of a 6-year-old Japanese boy with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. He had hypoketotic hypoglycaemia, exercise- and fasting-induced lethargy, hepatomegaly and cardiomegaly. Significant laboratory findings included elevated plasma levels of creatine phosphokinase and acyl-carnitine and a fatty liver at biopsy suggesting a diagnosis of VLCAD deficiency. CONCLUSION: The diagnosis of very long-chain acyl-CoA dehydrogenase deficiency was supported by the results of acyl-CoA dehydrogenase activity for C8 and C16 fatty acids in skin fibroblasts from the patient. Treatment with medium chain triglycerides and L-carnitine in the diet improved his hepatomegaly and cardiomegaly.

Acyl-CoA Dehydrogenase, Long-Chain↗

PubMed2000

Human presupplementary motor area is active before voluntary movement: subdural recording of Bereitschaftspotential from medial frontal cortex.

Bereitschaftspotential (BP) was recorded directly from the right supplementary motor area proper (SMA-proper) and its rostral part by chronically implanted subdural electrodes in three patients with intractable focal motor seizure. Cortical electrical stimulation of the SMA-proper revealed the somatotopy as previously reported, and the supplementary negative motor area (SNMA) was identified just anterior to the SMA-proper in two of three cases. In patient 1, eight kinds of simple movements, i.e., left and right middle finger extension, left arm abduction, left and right foot dorsiflexion, left knee extension, tongue protrusion and saccadic eye movement, were studied to record BP. In patient 2, three kinds of movements, i.e., left and right middle finger extension and left foot dorsiflexion, were adopted as movement tasks. In patient 3, four kinds of movements, i.e., left and right middle finger extension and left and right foot dorsiflexion, were adopted. In the SMA-proper, somatotopically distributed BP preceding movements were observed in all three patients. In the SNMA and its rostrally adjacent areas, "SNMA-plus" BPs were generated invariably regardless of the sites of movement. There was no significant difference in the onset time of BPs between the SMA-proper and the SNMA-plus. The present findings suggest that the SNMA-plus is more consistently involved in the preparation for various simple movements than the SMA-proper. This functionally independent region (SNMA-plus) just rostral to the SMA-proper most likely corresponds to a part of the presupplementary motor area which was originally defined in nonhuman primates. Since a part of this area elicited the inhibition of various movements by cortical stimulation, and since it generated BPs regardless of the sites of movement, it may play a higher role in the movement preparatory process than the SMA-proper.

Adult↗

PubMed2000

Inflammatory pseudotumor of the liver diagnosed by needle liver biopsy under ultrasonographic tomography guidance.

Inflammatory pseudotumor of the liver is a rare benign lesion, but exploratory laparotomy and a hepatectomy are often performed unnecessarily after various misdiagnoses, including liver abscess, hepatocellular carcinoma, metastatic liver tumor, and cholangiocarcinoma. We present a case of hepatic inflammatory pseudotumor in a 17-year-old man in whom diagnosis was confirmed by liver needle biopsy under ultrasonographic tomography (UST) guidance. He had complained of fever and right hypochondralgia 2 months after being operated for appendicitis. He was admitted to our hospital because of the persistence of these symptoms and the presence of a hepatic mass lesion detected by UST. He had hepatomegaly, with tenderness; leukocytosis and elevated erythrocyte sedimentation rate and C-reactive protein level were noted. UST showed a hypoechoic mass in the liver and pre-contrast computerized tomography (CT) revealed a low-density area with an ill defined margin, which was barely enhanced by the contrast medium. On the basis of the patient's clinical symptoms and the laboratory data and imaging studies, the presence of a liver abscess was suspected and antibiotics were administered. One month after the initiation of the antibiotic therapy, UST demonstrated that the portal vein had dilated serpiginously and penetrated into the mass. As the heterogeneous appearance displayed by post-enhanced CT indicated the need for a differential diagnosis of the hepatic mass lesion to rule out hepatocellular carcinoma, percutaneous needle biopsy was performed, under UST guidance. Histopathological examination demonstrated marked infiltration of plasma cells and fibrosis, findings which were consistent with those of hepatic inflammatory pseudotumor. There was a spontaneous reduction of the hepatic pseudotumor without continuous antibiotics and this reduction was documented on follow-up UST and CT.

Adolescent↗

PubMed2000

Viability of cryopreserved semilunar valves: an evaluation of cytosolic and mitochondrial activities.

BACKGROUND: Despite long-standing, widespread use of cryopreserved allografts, the basic cellular biology of these tissues is still yet unknown. The present investigation was undertaken to study cryopreserved heart valves from the standpoint of cytosolic esterase and mitochondrial dehydrogenase activities. METHODS: Cryopreserved porcine aortic cusps were observed in an unfixed fresh condition with a confocal laser scanning microscope using fluorescent dye. Porcine cusps and cultured human umbilical vein endothelial cells were divided into three groups, including fresh, cold-preserved, and cryopreserved specimens, and cytosolic esterase activity and mitochondrial dehydrogenase activity were analyzed in each. RESULTS: Confocal laser scanning microscope findings disclosed a widely distributed fluorescence in the cusp. Cytosolic esterase activity within human umbilical vein endothelial cells (28%+/-9.0%) after cryopreservation was significantly less than that it was in the cusps (72%+/-21%). Mitochondrial dehydrogenase activity of cryopreserved human umbilical vein endothelial cells and that of cusps fell to 44%+/-6.1% and 64%+/-17% respectively; the difference between the two values was not significant. CONCLUSIONS: Cryopreservation appeared to produce serious damage to cytosolic and mitochondrial functions of endothelial cells. The cytosolic function of cusps, mainly consisting of fibroblasts, was comparatively preserved after cryopreservation, but mitochondrial function of the cusps was more diminished.

Animals↗

PubMed2000

Negative NO3- difference in human coronary circulation with severe atherosclerotic stenosis.

To examine whether or not the levels of NOx (nitrite; NO2- and nitrate; NO3-) in coronary circulating blood reflect endothelial dysfunction due to coronary atherosclerosis, NOx levels in plasma obtained from ostium of left coronary artery and coronary sinus of patients who complained of chest pain were evaluated in relation to their coronary angiographic findings. Prior to the study, a HPLC-Griess system for NOx measurement was critically evaluated. This system has a detection limit of 0.1 microM of NO2- and NO3- by 10 microl of loading and was able to distinguish a difference of 0.1-0.2 microM of these substances. Heparin (1 U/10 microl) did not affect the detective and discriminative abilities. NO3- difference, calculated from sino-arterial difference of NO3-, was almost zero (-0.2 +/- 0.2 microM) in patients with either normal coronary arteries or mild organic coronary stenosis (< or = 20% narrowing), while a significant negative value (-5.9 +/- 1.7 microM) was obtained from patients with significant stenosis (> or = 70% narrowing) in the left coronary arteries. These results demonstrate reliable ability on the HPLC-Griess system in evaluating NO2- and NO3- in biological samples, and that the negative NO3- difference through coronary circulation may reflect endothelial dysfunction in the patients with coronary atherosclerosis with severe organic stenosis.

Chromatography, High Pressure Liquid↗

PubMed2000

Behavioral and neurochemical alterations following repeated phencyclidine administration in rats with neonatal ventral hippocampal lesions.

Exposure to chronic phencyclidine (PCP) has been reported to mimic certain aspects of schizophrenia in normal subjects as well as to exacerbate symptoms in schizophrenic patients. Analogous to schizophrenics, adult rats with neonatal ventral hippocampal (VH) lesions have been shown to display enhanced sensitivity to both stress and psychostimulants. In order to examine whether repeated PCP treatment can modulate behavior when administered to neonatal VH-lesioned animals, we examined locomotor activity and immobility time in the forced swimming test (FST) in neonatal VH-lesioned rats following repeated PCP treatment. Receptor autoradiography studies were also performed for dopamine (DA) and N-methyl-D-aspartate (NMDA) receptors to identify neurochemical correlates of the altered behavior in these animals. Though repeated PCP administration resulted in increased levels of locomotor activity and rearing in both VH-lesioned as well as sham rats, the effects were much more enhanced in the lesioned rats compared to sham. However, repeated PCP treatment induced hypolocomotion during the habituation period in both sham and lesioned rats. In the FST paradigm, lesioned rats displayed an altered retention of acquired immobility. Repeated PCP administration increased DA D1-like receptors in the caudate-putamen in lesioned rats and decreased striatal D2-like receptors in both sham and lesioned rats. Moreover, repeated PCP administration in lesioned rats decreased NMDA binding sites in the prefrontal cortex while increasing labelling in the subcortical regions. These results suggest that repeated administration of PCP can qualitatively and quantitatively affect behaviors in neonatal VH-lesioned rats related to abnormal neurodevelopmental processes presumably via prefrontal glutamatergic and subcortical dopaminergic dysfunctions.

Animals↗

PubMed2000

A case of chronic hepatitis C developing insulin-dependent diabetes mellitus associated with various autoantibodies during interferon therapy.

We report a case of chronic hepatitis C presenting insulin-dependent diabetes mellitus (IDDM) associated with various autoantibodies including possible anti-insulin receptor antibody (AIRA) during interferon (IFN) therapy. A 57-year-old man having chronic hepatitis C virus (HCV) infection with chronic thyroiditis received IFN therapy. The thyroid function was well-controlled by administration of thyroid hormone, although thyroid autoantibodies were positive. At 15 weeks after starting IFN (reaching 530 million units of total dose), marked thirst happened, with increased fasting plasma glucose level (488 mg/dl) and decreased daily urinary C peptide immunoreactivity level (less than 4.2 microg/day). IDDM occurred with anti-nuclear antibody (ANA), anti-DNA antibody and possible AIRA, and thyroid autoantibodies titers increased, but without pancreatic islet cell antibody and anti-glutamic acid decarboxylase antibody. Administration of IFN was stopped and insulin treatment was started, but plasma glucose level was not controlled well. AIRA became negative 2 months later, however, insulin antibody (IA) was positive when tested after 18 months. Serum HCV RNA has been negative, and a normal level of serum transaminase has been observed since IFN therapy. It is likely that IFN therapy induced the immunological disturbance and resulted in occurrence of various autoantibodies and IDDM in the patient.

Antibodies, Antinuclear↗

PubMed2000

Event-related potentials elicited by wrong terminal notes: effects of temporal disruption.

Wrong terminal notes of familiar musical phrases are known to elicit a large positive deflection of the event-related potential (ERP). The present study examined whether the effect of wrong terminal notes on ERP was modulated by the timing of their occurrence. Sixteen non-musicians were asked to rate the congruity of the endings of 50 well-known musical phrases. Four different types of endings were made for each phrase by manipulating the timing (well-timed vs. delayed for 750 ms) and pitch (correct vs. wrong) of the last note orthogonally. These ending patterns were presented equiprobably in an unpredictable order. Wrong notes elicited large late positive waves irrespective of the timing of occurrence. When the notes were delayed, however, the positive waves were reduced in amplitude to about 50% of those elicited by well-timed notes. These results suggest that the temporal (rhythmic) structure of musical phrases strongly influences the processing of melodic information.

Adult↗