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N Kato

Publications and source records attributed to N Kato.

At least 55 records · Page 3Linked to original sources
PubMed2003

Hepatitis A virus VP3 may activate serum response element associated transcription.

BACKGROUND: Hepatitis A virus (HAV) infection is a major public health problem worldwide. The infection does not induce any visible cytopathic effects or interfere with macromolecular synthesis in host cells. However, the hepatitis B and C viruses have recently been reported to activate intracellular signals. To clarify the effects of HAV infection on intracellular signalling, we examined the influence of 9 FLAG-tagged HAV proteins (VP2, VP3, VP1-2A, 2B, 2C, 3A, 3BC, 3C and 3D) on signal transduction pathways. METHODS: Viral protein expression vectors were co-transfected into HeLa cells with reporter plasmids controlled by a synthetic promoter containing direct repeats of the cyclic AMP response element (CRE), serum response factor (SRF), activator protein 1 (AP-1), nuclear factor kappaB (NF-kappaB) or serum response element (SRE). Cells were harvested 42 h after transfection and luciferase assays were performed. Viral protein activation twice that of the control was defined as significant. RESULTS: VP3 induced an SRE-associated signal 2.2 +/- 0.3 times higher than that of control. VP3 did not activate CRE-, SRF-, AP-1- or NF-kappaB- associated signalling. The other HAV proteins tested also failed to induce these pathways. CONCLUSIONS: HAV interacts with the host signalling mechanism, and HAV VP3, different from HBX and hepatitis C core protein, may activate only SRE-associated intracellular signalling, a pathway associated with cell proliferation and differentiation.

Blotting, Western↗
PubMed2003

A case of acute renal failure due to rhabdomyolysis, associated with non-autoimmune fulminant type 1B diabetes mellitus.

A 38-year-old man developed severe diabetic ketoacidosis complicated with rhabdomyolysis and acute renal failure after presenting hyperglycemic symptoms for 4 days. Initial investigation showed significant hyperglycemia (blood glucose level 1,593 mg/dl) with a relatively low level of HbA1c (7.0%) and a high pancreatic enzyme concentration without any signs of pancreatitis. Diabetes-related antibodies were absent except for the anti-glutamic acid decarboxylase antibody, which disappeared later on. Pancreatic biopsy examination showed the lack of insulin-secreting cells, without insulitis. These findings were almost consistent with non-autoimmune fulminant type 1B diabetes. The patient remained dependent on dialysis for 1 month, then his renal function recovered. In patients with this type of diabetes, the onset of overt diabetes, frequently accompanied with severe diabetic ketoacidosis, is rapid, hence, early detection, quick diagnosis and immediate treatment of this novel type of diabetes are important in the rescue of these patients.

Acute Kidney Injury↗
PubMed2002

1H-MR spectroscopy and gray matter volume of the anterior cingulate cortex in schizophrenia.

Schizophrenic and normal control subjects were examined using both H-magnetic resonance spectroscopy (MRS) and structural MR imaging, in order to accurately assess the partial volume within the spectroscopic volume of interest (VOI) in the anterior cingulate cortex. The gray matter volume within VOI correlated positively with the N-acetyl-aspartate (NAA) to choline (Cho) ratio in schizophrenics only, not in controls. Schizophrenic patients had a reduced NAA/Cho ratio and an elevated Cho/creatine ratio compared to controls after the partial volume effect was eliminated. There was a significant negative correlation between the NAA/Cho ratio and the severity of blunted affect symptom in schizophrenics. These results provide further support to the idea that the measures of H-MRS indicate not only neuronal loss but also neuronal dysfunction in schizophrenia.

Adult↗
PubMed2002

Production of active bovine cathepsin C (dipeptidyl aminopeptidase I) in the methylotrophic yeast Candida boidinii.

The heterologous production of active bovine cathepsin C (CTC; dipeptidyl aminopeptidase I) was investigated. Attempts to express CTC in Escherichia coli were hampered by formation of inclusion bodies that were partially degraded. To overcome this impediment, secretion of recombinant CTC was attempted in the methylotrophic yeast Candida boidinii. A DNA fragment encoding bovine procathepsin C was synthesized based on preferred codon usage in C. boidinii and placed downstream of the C. boidinii proteinase A signal sequence resulting in secretion of active CTC into the culture medium. The gene was expressed under the control of the methanol-inducible formate dehydrogenase gene promoter. Production levels were significantly improved by using a protease-deficient strain, changing medium composition, and by lowering the temperature of induction. When the recombinant C. boidinii was grown for 90 h in a jar-fermenter, active CTC was secreted with a yield of up to approximately 12 mg/l.

Amino Acid Sequence↗
PubMed2002

Alterations of ubiquitin immunoreactivity in the hippocampal formation after perforant pathway lesion.

Immunohistochemical techniques were employed to examine the changes in free ubiquitin within the hippocampus 1, 3, 7, 14, and 30 days after a unilateral perforant pathway lesion occurred in the rat brain. Immunoreactivity for ubiquitin was remarkably decreased in the cell body and proximal dendrites of neurons throughout the hippocampus ipsilateral to the lesion at 1 day post-lesion. At 3 days post-lesion, ubiquitin immunoreactivity was recovered in interneurons in the whole hippocampus as well as in mossy cells in the hilar region, although granule cells in the dentate gyrus and pyramidal cells in the CA1 subfield remained unlabeled, and pyramidal cells in the CA3 subfield demonstrated only weak immunoreactivity. In addition, we observed an increase in ubiquitin immunolabeling of the hilar neuropil ipsilateral to the lesion at 1 and 3 days post-lesion, and a decrease in immunolabeling in the inner portion of the molecular layer at 3 days post-lesion. All these alterations were transient, and by 7 days post-lesion, ubiquitin immunoreactivity was indistinguishable in the hippocampus ipsilateral to the lesion, compared to the controls. Immunoblot analysis also revealed a decrease in the amount of ubiquitin in the hippocampus ipsilateral to the lesion 1 and 3 days post-lesion. These data suggest that deafferentation of the perforant pathway results in transient reduction in free ubiquitin of the hippocampus, and that the ubiquitin system is involved in hippocampal plasticity following perforant lesions.

Animals↗
PubMed2002

Circulating corticosterone alters the rate of neuropathological and behavioral changes induced by trimethyltin in rats.

When trimethyltin (TMT) is administered to rats, the plasma corticosterone concentration rises transiently 3 to 4 days later. We examined whether plasma corticosterone plays a causative role in the TMT-induced impairment of the hippocampus as assessed by pathological and behavioral tests. TMT-administered rats were supplementally treated with either adrenalectomy or metyrapone (twice daily for the first 7 days after TMT) in order to permanently deplete or transiently suppress circulating corticosterone. Loss of pyramidal cells in the CA1 and CA3 fields, mossy fiber sprouting, and impairment of spatial memory were observed after TMT intoxication. Adrenalectomy apparently aggravated both the hippocampal damage and the spatial memory impairment induced by TMT treatment. The TMT+metyrapone treatment groups exhibited a significant reduction in pyramidal cells in both the CA1 and the CA3 regions. However, the neuronal damage in CA1 was significantly different between the TMT and the TMT+metyrapone groups. Metyrapone significantly reduced the TMT-induced damage to pyramidal cells in CA1, but not CA3, and it also abolished mossy fiber sprouting. TMT-induced learning impairment and hyperactivity were alleviated by metyrapone treatment. It is thus concluded that both the high levels of corticosterone induced by TMT and the pathologically low levels of corticosterone induced by adrenalectomy will worsen the consequences of TMT.

Adrenalectomy↗
PubMed2002

Emergence of a functional coupling between inositol-1,4,5-trisphosphate receptors and calcium channels in developing neocortical neurons.

Cortical pyramidal neurons are considered to be less excitable in the immature cortex than in adults. Our previous report revealed that a negative feedback regulation of membrane excitability is highly correlated with a novel form of calcium release from inositol-1,4,5-trisphosphate (IP(3))-sensitive calcium stores (IP(3)-assisted calcium-induced calcium release) in neocortical pyramidal neurons under muscarinic cholinergic activation. As a step to understand the ground for the low membrane excitability in immature tissue, we examined development of IP(3)-assisted calcium-induced calcium release. In visual cortex neurons from 'juvenile' rats (2-3 weeks of age), an enhancement of spike-frequency adaptation occurred at high spike-frequencies (16-22 Hz), whereas the reduction was observed at low frequencies (6-10 Hz). IP(3)-assisted calcium-induced calcium release occurred at the higher frequencies only. In 'early' postnatal tissue (1 week of age), by contrast, at neither high nor low frequencies did this form of calcium release occur, and muscarinic cholinergic activation always induced a reduction of spike-frequency adaptation at any spike-frequencies. The mechanism for the failure of induction of IP(3)-assisted calcium-induced calcium release in 'early' postnatal tissue was investigated. Both an ample supply of calcium influx, elicited by higher frequency spike trains, and a supplementary injection of IP(3) through whole-cell pipets, combined together or applied alone, failed to enable IP(3)-assisted calcium-induced calcium release in 'early' postnatal tissue. Muscarinic cholinergic activation alone induced a conventional IP(3)-induced calcium release similar to that observed in neurons from 'juvenile' tissue. Together, it is most likely that functional IP(3)Rs and calcium channels are already present and functional, but are not yet adequately assembled to allow IP(3)-assisted calcium-induced calcium release in cortical pyramidal neurons from rats of 1 week old.

Action Potentials↗
PubMed2002

A distinct form of calcium release down-regulates membrane excitability in neocortical pyramidal cells.

We reported a novel type of calcium release from inositol-1,4,5-trisphosphate (IP(3))-sensitive calcium stores synergistically induced by muscarinic acetylcholine receptor (mAchR)-mediated increase in IP(3) and action potential-induced calcium influx (IP(3)-assisted calcium-induced calcium release, IP(3)-assisted CICR). To clarify its functional significance, the effects of IP(3)-assisted CICR on spike-frequency adaptation were examined in layer II/III neurons from rat visual cortex slices. IP(3)-assisted CICR was enabled with a high concentration of the mAchR agonist carbachol (10 microM). The magnitude of this CICR was the more augmented at higher firing frequencies. With 10 microM carbachol, spike-frequency adaptation was reduced for spike trains at 'low' firing frequencies (6-10 Hz), but was rather enhanced at 'high' firing rates (16-22 Hz): excitability was down-regulated at 'high' frequencies. With 1 microM carbachol, by contrast, IP(3)-assisted CICR failed to occur, and spike-frequency adaptation was always reduced at any spike frequencies. Intracellular injection of the IP(3) receptor blocker heparin prevented both the mAchR-mediated occurrence of IP(3)-assisted CICR and enhancement of spike-frequency adaptation with 10 microM carbachol. Both of these mAchR-mediated effects were reproduced by intracellular IP(3) injection, and were shown to be associated with each other by simultaneous recordings of membrane potential and intracellular calcium increase. We propose that IP(3)-assisted CICR offers a novel way to protect these cortical neurons from hyperexcitability and presumably from excitotoxic cell death.

Action Potentials↗
PubMed2002

Differential changes in messenger RNA expressions and binding sites of neuropeptide Y Y1, Y2 and Y5 receptors in the hippocampus of an epileptic mutant rat: Noda epileptic rat.

The anti-convulsive effects of neuropeptide Y have been suggested in several animal models of epilepsy. We have found the sustained increase of neuropeptide Y contents and the seizure-induced elevation of hippocampal messenger RNA in a novel spontaneous epileptic mutant rat: Noda epileptic rat. In the present study, we investigated the change of neuropeptide Y Y1 and Y2 receptor messenger RNA expressions and binding sites in the hippocampus following a spontaneous generalized tonic-clonic seizure of Noda epileptic rat. Furthermore, the binding sites of a more recently isolated receptor subtype, neuropeptide Y Y5 receptors, were also evaluated by receptor autoradiography. A marked elevation of neuropeptide Y immunoreactivity in the mossy fiber, and Y2-receptor up-regulation in the dentate gyrus were observed in the hippocampus of Noda epileptic rat, which coincided with the previous results of the other epileptic models. In contrast, Y1-receptor down-regulation was not found after a spontaneous seizure of Noda epileptic rat while this occurs in kindling and after kainic acid-induced seizures. [125I][Leu31, Pro34]peptide YY/BIBP 3226-insensitive (Y5 receptor) binding sites in CA1 stratum radiatum were significantly decreased following a spontaneous seizure of Noda epileptic rat. The present results suggest that a spontaneous seizure of Noda epileptic rat induces significant changes in neuropeptide Y-mediated transmission in the hippocampus via Y2 and Y5 receptors, but not Y1 receptors. Therefore, specific subset of neuropeptide Y receptor subtypes might be involved in the epileptogenesis of Noda epileptic rat.

Animals↗
PubMed2002

Decreased cerebral haemodynamic response to cognitive and physiological tasks in mood disorders as shown by near-infrared spectroscopy.

BACKGROUND: Hypofrontality has been demonstrated in mood disorders by functional brain imaging methods such as positron emission tomography. However, the neurobiological basis of hypofrontality has not been well clarified. Near-infrared spectroscopy (NIRS) is a non-invasive technique for continuous monitoring of alterations in oxygenated (oxyHb) and deoxygenated (deoxyHb) haemoglobin using near-infrared light, which penetrates biological tissues. METHODS: We used NIRS during cognitive and physiological tasks to investigate alterations of haemoglobin oxygenation in the frontal region of euthymic patients with mood disorders (major depressive disorder (MD) and bipolar disorder (BP)) and in controls. RESULTS: The increase of oxyHb during a verbal fluency task was significantly less in the MD and the BP groups than in the controls. The MD group showed a significantly smaller decrease of oxyHb during hyperventilation than the controls. The BP group also showed a similar trend. CONCLUSIONS: These findings suggest that the hypofrontality in mood disorders may be associated with a poor response in the cerebral blood vessels to neuronal and chemical stimuli.

Adult↗
PubMed2002

Glucosamine:fructose-6-phosphate aminotransferase: gene characterization, chitin biosynthesis and peritrophic matrix formation in Aedes aegypti.

Glucosamine:fructose-6-phosphate aminotransferase (GFAT) catalyses the formation of glucosamine 6-phosphate and is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. The final product of the hexosamine pathway, UDP-N-acetyl glucosamine, is an active precursor of numerous macromolecules containing amino sugars, including chitin in fungi and arthropods. Chitin is one of the essential components of insect cuticle and peritrophic matrix. The peritrophic matrix is produced in the midgut of mosquitoes in response to bloodfeeding, and may affect vector competence by serving as a physical barrier to pathogens. It is hypothesized that GFAT plays a regulatory role in biosynthesis of chitin and peritrophic matrix formation in insects. We cloned and sequenced the GFAT gene (AeGfat-1) and its 5' regulatory region from Aedes aegypti. There is no intron in AeGfat-1 and there are two potential transcription start sites. AeGfat-1 cDNA is 3.4 kb in length and its putative translation product is 75.4 kDa. The amino acid sequence of GFAT is highly conserved in lower and higher eukaryotes, as well as in bacteria. AeGfat-1 message is constitutively expressed but is gradually up-regulated in the midgut after bloodfeeding. The putative regulatory region of the gene contains the ecdysone response element, E74, and Broad complex motifs, similar to what is found in the glutamine synthetase gene in Ae. aegypti. Results suggest that Ae. aegypti GFAT-1 may have a regulatory role in chitin biosynthesis and peritrophic matrix formation, and probably is under the regulation of ecdysteroids.

5' Untranslated Regions↗
PubMed2002

Superior mesenteric vein thrombosis presented transient false positivity for lupus anticoagulant under heparin treatment.

A 24-year-old Japanese man was admitted because of massive haematemesis and melaena with persistent abdominal pain. Markedly bloody ascites and severely oedematous small intestine were recognized, and angiography then revealed superior mesenteric vein thrombosis. After resection of the necrotic small intestine, continuous intravenous infusion of heparin and urokinase was performed. This patient had no familial or personal history of thrombosis. On the 15th day after operation, an initial search for lupus anticoagulant revealed that the prothrombin time (PT) ratio and dilute activated partial thromboplastin time (aPTT) were positive under heparin treatment, without evidence of rheumatic or connective tissue disease. Thrombocytopenia was observed with a nearly normocellular bone marrow. A follow-up examination 1 year later still revealed an increased aPTT. However, all tests for antiphospholipid antibodies had been negative including dilute aPTT for about 2 years since the 15th day after operation. These findings suggest that, in this patient, superior mesenteric vein thrombosis has not been associated with primary antiphospholipid syndrome but is probably idiopathic. Positive tests for lupus anticoagulant in the initial period may be unreliable due to heparin treatment.

Adult↗
PubMed2002

Analysis of mixed chimerism in patients after allogeneic stem cell transplantation using a capillary electrophoresis system.

We analyzed mixed chimerism (MC) after allogeneic stem cell transplantation (SCT) using a capillary electrophoresis system with four kinds of fluorescence-labeled primers for microsatellites (D3S1359, D6S89, ACTBP2, HGH). The sensitivities of all microsatellites were at least 3%. The present method is sufficiently rapid: only 3-4 h are needed to perform all the procedures. For analysis of MC in 30 patients who had undergone allogeneic SCT, heterozygosity of all microsatellites was over 88% and informativeness of ACTBP2 and HGH was over 73%. We analyzed MC using this technique to determine whether it was useful for prediction of the prognosis of 22 patients who had undergone allogeneic SCT. MC was more frequently observed in patients who were treated without total body irradiation (TBI) than in patients who were treated with TBI (p = 0.009). MC was also seen in a larger percentage of patients without acute graft-versus-host disease (p = 0.027). Six patients developed graft failure or relapse among 12 patients with MC. The graft failure or relapse was higher in patients with MC than in patients with complete chimerism (CC) (p = 0.009) especially if they were over 30 years of age (p = 0.0005). In contrast, graft failure or relapse was not higher in patients with MC compared with patients with CC under 30 years of age (p = 0.78). These results show that MC is an important predictive factor, especially in patients over 30 years of age.

Adolescent↗
PubMed2001

Changes in the GABA-ergic system induced by trimethyltin application in the rat.

Ingestion of trimethyltin (TMT) produces mental confusion and temporal lobe seizures in humans. In rats, it causes increased seizure susceptibility, hyperactivity, aggression, learning impairment, and neuronal loss especially of hippocampal CA3c pyramidal cells and in the piriform cortex. As some of these symptoms may be due to impaired inhibitory neurotransmission, mRNA levels of the nine major GABA(A) receptor subunits, of GABA(B) receptors 1 and 2, and the 65- and 67-kD glutamate decarboxylase (GAD) variants were investigated by in situ hybridization 2, 5, and 16 days after TMT administration. GAD-65 mRNA levels were enhanced in hippocampal interneurons by up to 46% 5 days after TMT application, suggesting increased activity of respective neurons. In the granule cell layer, only the GABA(A) receptor subunit delta mRNA was altered (decreased by 48%). In the hippocampal sector CA3c and in the piriform cortex, mRNA levels of GABA(A) receptor subunits alpha1, alpha5, beta1, beta2, beta3, gamma2 and of both GABA(B) receptors declined (by 46-72%) after 5-16 days, being consistent with the extensive cell loss. In contrast, subunit alpha2 mRNA levels decreased already after 2 days at an extent exceeding the cell loss in CA3. Subunit alpha4 mRNA levels increased (about two-fold) in surviving CA3 neurons. In sector CA1, mRNA levels of subunits alpha1, alpha5, beta2, beta3, and gamma2 decreased by 35-54% in spite of only a minor (9%) cell loss. The data indicate neurodegeneration related decreases in mRNA levels in sector CA3 and piriform cortex, whereas decreases in sector CA1 may be a consequence of impaired excitatory input to this area.

Aggression↗
PubMed2001

Systematic analysis of the TGF-beta-Smad signaling pathway in gastrointestinal cancer cells.

The transforming growth factor-beta (TGF-beta)-Smad signaling pathway has an important role in carcinogenesis. To study the frequency and mechanism of functional impairment of this pathway in human gastrointestinal cancers, we used a reporter assay to examine the response of 38 cell lines (11 colorectal, 9 pancreatic, 10 gastric, and 8 hepatic cancers) to TGF-beta. We then analyzed TGF-beta type II receptor (T beta RII) gene, immunoblots of Smad4, and restoration of the pathway by rescuing T beta R or Smad. We observed impaired signaling in 91% of colorectal, 67% of pancreatic, and 40% of gastric cancer cell lines, but in none of the hepatic cancer cells. We suggest that this pathway does not function as a tumor suppressor in hepatic carcinogenesis. The impairment is due to inactivation of T beta RII and Smad4 in colorectal and pancreatic cancers. However, because the signal was not recovered by rescuing T beta R or Smad genes in TGF-beta-response-defective gastric cancer cell lines, we suggest that novel molecules or mechanisms are involved in the impaired pathway in some gastric cancers.

Blotting, Western↗
PubMed2001

T cell responses to major membrane protein II (MMP II) of Mycobacterium leprae are restricted by HLA-DR molecules in patients with leprosy.

Major membrane protein II (MMP II) of Mycobacterium leprae (M. leprae) is a 22kDa protein inducing humoral immune response in leprosy patients. MMP II-specific bulk T cell lines were established from leprosy patients to determine major T cell epitopes in MMP II and to evaluate lymphokine production induced by MMP II. These bulk T cell lines reacted to one or more peptides in the locus of amino acid residues from 23 to 109 of MMP II. The proliferative responses of all T cell lines were mainly inhibited by the addition of anti-DRB1 mAb. Many bulk T cell lines induced IFN-gamma, IL-5, but not IL-4. However, it was not possible to distinguish the LL or TT types of leprosy based on the pattern of T cell epitopes and the lymphokine productivity in the responses against MMP II. Thus, it appears that T cell response to MMP II is restricted by the HLA-DRB1 molecule, but not by DQ and DP molecules, which results in the induction of IFN-gamma production.

Amino Acid Sequence↗
PubMed2001

The reaction of fullerene C(60) with phthalazine: the mechanochemical solid-state reaction yielding a new C(60) dimer versus the liquid-phase reaction affording an open-cage fullerene.

The reaction of fullerene C(60) with phthalazine was studied both in solution and in the solid state using the high-speed vibration-milling technique. The reaction in solution gave open-cage fullerene derivative 1 in 44% yield by a one-pot reaction. In contrast, the solid-state reaction afforded dimeric derivative 2 as the sole product. Dimeric derivative 2 was found to undergo intramolecular [2 + 2] cycloaddtion between the two C(60) cages located in close proximity to give a new C(60) dimer 6 in quantitative yield. The structures of these new derivatives of C(60) were determined by spectroscopic methods, and the electrochemical behavior of 2 and 6 was also studied.

Journal Article↗