Biomedical subjects

K Mizoguchi

Publications and source records attributed to K Mizoguchi.

At least 19 recordsLinked to original sources

PubMed2003

Chronic stress attenuates glucocorticoid negative feedback: involvement of the prefrontal cortex and hippocampus.

Disruption of the glucocorticoid negative feedback system is observed in approximate one half of human depressives, and a similar condition is induced in animals by chronic stress. This disruption is thought to involve down-regulation of glucocorticoid receptors (GRs) in the feedback sites of the brain. However, the responsible site of the brain has not been well elucidated. Here we examined the effects of chronic stress induced by water immersion and restraint (2 h/day) for 4 weeks followed by recovery for 10 days on the GR levels in the prefrontal cortex (PFC), hippocampus, and hypothalamus of rats using a Western immunoblot technique. In the PFC, the cytosolic GR levels were decreased, but the nuclear GR levels were not changed. In the hippocampus, the levels of cytosolic and nuclear GRs were increased. However, there were no marked changes in the GR levels in the hypothalamus. The changes in the cytosolic GR levels were confirmed at the mRNA level by an in situ hybridization technique. We next examined the suppressive effects of dexamethasone (DEX) infusions into these regions on the circulating corticosterone levels. When DEX was infused into the PFC or hippocampus of the chronically stressed rats, the suppressive response to DEX was abolished, but the response was normal in the hypothalamus. In addition, when DEX was injected systemically to the chronically stressed rats, the suppressive response to DEX was significantly attenuated. These results suggest that the abnormal changes in GRs in the higher centers of the hypothalamo-pituitary-adrenal axis are involved in the chronic stress-induced attenuation of the feedback. Since dysfunction of the PFC or hippocampus is implicated in the pathogenesis of depression, the present findings would help to understand the mechanisms underlying the disrupted feedback system and its relation to brain dysfunction in depression.

Animals↗

PubMed2002

Secretion of natriuretic peptides caused by an epileptic attack.

OBJECTIVE: To describe clinical features of a patient with secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) during an epileptic attack. PATIENT: A 65-year-old woman experienced frequent bouts of polyuria, pyrexia and general fatigue after several years of a cerebral contusion involving the left fronto-temporal lobe caused by a traffic accident. Her urine output and urinary sodium excretion increased, and plasma ANP and BNP concentrations were markedly high during each attack. Electroencephalography (EEG) showed serial seizure discharge in the left anterior temporal region during the attacks, indicative of epileptic focus. CONCLUSION: ANP and BNP secretions probably were triggered by epileptic stimulation on the diencephalon beyond the focus.

Aged↗

PubMed2002

Up-regulation of calcitonin gene-related peptide receptors underlying elevation of skin temperature in ovariectomized rats.

We investigated the mechanism for the augmentation of the calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature in ovariectomized (OVX) rats. I.v. injection of alphaCGRP (10 micro g/kg) elevated skin temperature of the hind paws. The elevation was significantly greater in OVX rats than in sham-operated rats and was inhibited by pretreatment with human CGRP(8-37) (100-1000 micro g/kg i.v.), a CGRP receptor antagonist, in a dose-dependent manner. In addition, ovariectomy not only potentiated vasorelaxation due to alphaCGRP but increased the number of CGRP receptors in mesenteric arteries. Further, the plasma concentration of endogenous CGRP was significantly lower in OVX rats. These results suggest that the low concentration of plasma CGRP due to ovarian hormone deficiency may induce the increase in the number of CGRP receptors due to up-regulation. Therefore, the increased number of CGRP receptors may be responsible for potentiation of exogenous alphaCGRP-induced elevation of skin temperature in OVX rats. The mechanism underlying the hot flashes observed in menopausal women may also involve, in part, the up-regulation of CGRP receptors following ovarian hormone deficiency.

Analysis of Variance↗

PubMed2002

Fate of coliphage in waste water treatment process and detection of phages carrying the Shiga toxin type 2 gene.

Abundances of phages specific to Escherichia coli in the wastewater treatment process were analyzed. Relatively abundant coliphages were detected in sewage influent. Phages in the influent were found both suspended in liquid phase and attached on the solid particles. Phage concentration was not reduced in the settling tank without chemical agglutination. Anaerobic followed by aerobic treatment of the sewage reduced concentration of suspended phages. Almost no phage was detected as a suspended form in the aerobic tank. Most of the phages were detected as attaching form and were excluded by aggregation with sludge. Using an experimental approach based on the detection of Shiga toxin 2 (Stx 2) gene by a phage enrichment culture followed by nested PCR, bacteriophages carrying Stx 2 gene were detected in the influent, settling tank, and anaerobic tank. It was revealed that the presence of phages carrying Stx 2 gene is common in sewage and these phages are effectively eliminated through sewage treatment process.

Coliphages↗

PubMed2001

Effect of chronic stress on cholinergic transmission in rat hippocampus.

We previously demonstrated that chronic stress impaired prefrontal cortex-sensitive working memory, but not reference memory. Since the hippocampal cholinergic system is also involved in these memories, we examined the effects of chronic stress on cholinergic transmission in the rat hippocampus. A microdialysis study revealed that the stress did not affect the basal acetylcholine release, but enhanced the KCl-evoked response. These results suggest that cholinergic transmission in the chronically stressed hippocampus does not contribute to working memory impairment, but it may be involved in maintenance of reference memory.

Acetylcholine↗

PubMed2001

Functional analysis of antibacterial activity of Bacillus amyloliquefaciens phage endolysin against Gram-negative bacteria.

To analyze the antibacterial activity of Bacillus amyloliquefaciens phage endolysin, nine deletion derivatives of the endolysin were constructed. Each deletion mutant was overexpressed, purified and characterized. The catalytic domain was located on the N-terminal region and the C-terminus had an affinity with the bacterial envelope. The enzymatic activity remained in spite of the deletion of the C-terminal 116-amino acid region; however, the antibacterial activity was lost. These results indicate that antibacterial action requires both the C-terminal cell-binding and the N-terminal enzymatic activities.

Anti-Bacterial Agents↗

PubMed2001

Intestinal ischemia induces late preconditioning against myocardial infarction: a role for inducible nitric oxide synthase.

OBJECTIVE: We tested the hypothesis that occlusion of the superior mesenteric artery induces late preconditioning against myocardial infarction and examined the effects of pharmacological modifiers of inducible nitric oxide synthase activity on the late preconditioning in anesthetized rats. METHODS: Rats underwent an intestinal ischemia preconditioning protocol (30 min occlusion of the superior mesenteric artery) or were sham-operated. They were subjected to a sustained 30 min of coronary occlusion and 180 min of reperfusion 24 h later. RESULTS: In rats receiving no pharmacological intervention, the percentage of myocardial infarct within the area at risk and left ventricle was 72+/-4% and 31+/-2%, respectively, in sham-operated rats, and these were significantly reduced to 44+/-4% and 23+/-2% (P<0.01) 24 h after intestinal ischemia preconditioning. Myeloperoxidase activity was significantly reduced by intestinal ischemia preconditioning. Administration of aminoguanidine (300 mg/kg, s.c.) or S-methylisothiourea sulfate (3 mg/kg, i.v.), both relative inducible NO synthase inhibitors, 60 or 30 min before sustained myocardial ischemia not only abolished the late preconditioning afforded by intestinal ischemia, but also inhibited the ability of intestinal ischemia preconditioning to significantly reduce neutrophil infiltration. A change in inducible NO synthase activity was not observed in normal myocardium 24 h after intestinal ischemia, but 30 min of coronary occlusion significantly increased the inducible NO synthase activity in the preconditioned group, which was abolished by aminoguanidine or S-methylisothiourea sulfate. CONCLUSIONS: These data provide pharmacological evidence that induction of inducible nitric oxide synthase, following intestinal ischemia, is associated with increased myocardial tolerance to infarction 24 h later.

Analysis of Variance↗

PubMed2001

Chronic stress differentially regulates glucocorticoid negative feedback response in rats.

Exposure to chronic stress is thought to play an important role in the etiology of depression. In this disorder, a disrupted negative feedback response to exogenous glucocorticoids on cortisol secretion has been indicated. However, the regulation of glucocorticoid negative feedback by chronic stress is not fully understood. In the present study, we investigated the effects of chronic stress administered by water immersion and restraint (2 h/day) for four weeks on the glucocorticoid feedback in rats. In the acutely (one-time) stressed rats, the basal plasma corticosterone (CORT) level was markedly elevated, remained at high levels for 5 h after the termination of stress, and then decreased. In the chronically stressed rats, the CORT level was initially elevated similarly, but rapidly decreased at 2 h. In the dexamethasone (DEX) suppression test, the peak CORT level in response to stress was not suppressed by DEX in the acutely stressed rats, but was significantly suppressed in the chronically stressed rats. In contrast, the suppressive effects of DEX on the basal CORT secretion in naive rats were attenuated in the chronically stressed rats. In the chronically stressed hippocampus, which plays an important role in the regulation of the glucocorticoid feedback response, the binding of [3H]DEX was decreased and the increased response of activator protein-1 induced by acute stress was abolished. These results suggest that chronic stress induces a hypersuppressive state for induced CORT secretion in response to acute stress, which is caused by partial habituation, coping, and adaptation to the stressor, whereas it induces a hyposuppressive state for the basal CORT secretion, which is caused by glucocorticoid receptor downregulation. These mechanisms may be involved in the stress-induced neural abnormalities observed in depression.

Adrenal Glands↗

PubMed2001

In vitro induction of apoptosis for nasal angiocentric natural killer cell lymphoma-derived cell line, NK-YS, by etoposide and cyclosporine A.

Epstein-Barr virus (EBV)-associated nasal T/natural killer (NK) cell lymphoma has often been reported in Asian countries and has been recently confirmed as a novel clinicopathological entity. The prognosis of advanced stage disease is quite poor and an effective chemotherapeutic modality is strongly advocated. We have established the novel cell line NK-YS, which preserves the original characteristics of EBV-associated nasal angiocentric T/NK cell lymphoma. Using this cell line, we investigated the induction of apoptosis by apoptosis-inducing agents, and expression of P-glycoprotein (P-gp), p53 and bcl-2 proteins. NK-YS showed resistance towards apoptosis-inducing agents and expressed bcl-2 and P-gp but not p53. To overcome this drug resistance, we added cyclosporine A (CsA) and these agents to culture media as a P-gp antagonist. The combination of CsA and etoposide or CsA and doxorubicin induced apoptotic cell death. These results indicated that P-gp-mediated drug resistance is an essential mechanism of drug resistance of the NK-YS cell line. Combined therapy of conventional anti-cancer agents with CsA may have an important place in the establishment of a curative therapy for disseminated nasal angiocentric NK cell lymphoma.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2001

Human cystinuria-related transporter: localization and functional characterization.

BACKGROUND: Cystinuria has been proposed to be an inherited defect of apical membrane transport systems for cystine and basic amino acids in renal proximal tubules. Although the mutations of the recently identified transporter BAT1/b(0,+)AT have been related to nontype I cystinuria, the function and localization of human BAT1 (hBAT1)/b(0,+)AT have not been well characterized. METHODS: The cDNA encoding hBAT1 was isolated from human kidney. Fluorescence in situ hybridization was performed to map the hBAT1 gene on human chromosomes. Tissue distribution and localization of expression were examined by Northern blot and immunohistochemical analyses. hBAT1 cDNA was transfected to COS-7 cells with rBAT cDNA, and the uptake and efflux of 14C-labeled amino acids were measured to determine the functional properties. The roles of protein kinase-dependent phosphorylation were investigated using inhibitors or activators of protein kinases. RESULTS: The hBAT1 gene was mapped to 19q12-13.1 on the human chromosome, which is the locus of nontype I cystinuria. hBAT1 message was expressed predominantly in kidney. hBAT1 protein was localized in the apical membrane of proximal tubules in human kidney. When expressed in COS-7 cells with a type II membrane glycoprotein rBAT (related to b(0,+)-amino acid transporter), hBAT1 exhibited the transport activity with the properties of amino acid transport system b(0,+), which transported cystine as well as basic and neutral amino acids presumably via a substrate exchange mechanism. BAT1-mediated transport was reduced by the protein kinase A activator and enhanced by the tyrosine kinase inhibitor. CONCLUSIONS: hBAT1 exhibited the properties expected for a transporter subserving the high-affinity cystine transport system in renal proximal tubules. The hBAT1 gene was mapped to the locus of nontype I cystinuria, confirming the involvement of hBAT1 in cystinuria.

ATP-Binding Cassette Transporters↗

PubMed2000

Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction.

Although the mechanism responsible for cognitive deficits in stress-related neuropsychiatric disorders has been obscure, prefrontal cortical (PFC) dopaminergic dysfunction is thought to be involved. In animals, the mesoprefrontal dopaminergic system is particularly vulnerable to stress, and chronic stress induces working memory impairment. However, the relation between the working memory impairment and altered dopaminergic activity in chronically stressed rats is unclear. Furthermore, the change of dopaminergic activity in the PFC induced by stress is thought to express as a stress response, not as a disorder of organic function. We have previously reported that chronic stress administered by water immersion and restraint for 4 weeks induces a organic disorder such as hippocampal neuronal degeneration. We therefore examined whether chronically stressed (4 weeks) and recovered (10 d) rats show a working memory impairment caused by reduced dopamine (DA) transmission in the PFC, as suspected in the neuropsychiatric disorders. The stress impaired the spatial working memory evaluated by T-maze task and induced a marked reduction of DA transmission concomitant with an increase in DA D1 receptor density in the PFC. This memory impairment was sufficiently ameliorated by intra-PFC infusion of 10 ng SKF 81297, a D1 receptor-specific agonist. Pretreatment with intraperitoneal injection of 20 microgram/kg SCH 23390, a D1 receptor antagonist, reversed the SKF 81297 response. These results indicate that chronic stress induces working memory impairment through a D1 receptor-mediated hypodopaminergic mechanism in the PFC. These findings provide important information for understanding of the mechanisms underlying PFC dysfunction in stress-related neuropsychiatric disorders.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Air embolism in the right coronary artery occurring during the left coronary angioplasty using the guiding catheter with a side hole.

Coronary air embolism is one of the inadvertent complications of coronary angioplasty. We report two rare cases of complicating air embolism in the right coronary artery occurring during control left coronary angiography using a guiding catheter with a side hole, just prior to a coronary intervention procedure for a left coronary artery lesion. The air seemed to be injected into the right coronary artery through the side hole. When we use an angiographic or guiding catheter with a side hole, we should be aware that an air embolism can occur in the contralateral coronary artery and should carefully and repeatedly perform aspiration of the catheter.

Aged↗

PubMed2000

Forms of vitamin B12 compounds containing sulfitoB12 in corbiculas.

Forms of vitamin B12 (B12) compounds in young and aged corbiculas were examined by bioautography using B12-requiring microorganisms combined with cellulose acetate membrane electrophoresis or high-performane liquid chromatography (HPLC). Both corbiculas (per 100 g) contained ca. 30 microg of cobalamin, a complete type of B12. Five known B12 compounds, adenosylB12 (AdoB12), methylB12, hydroxoB12, sulfitoB12 and cyanoB12, were identified by bioautography. Young corbicula contained more B12 compounds, assumed as methylB12, AdoB12 and sulfitoB12, as compared to aged corbicula. All of the B12 compounds detected around the location corresponding to those of methylB12, AdoB12 and sulfitoB12 in the bioautography were converted into compounds that behaved like hydroxoB12 after photolysis. Young corbicula was found to contain an unidentified B12 compound using bioautography combined with HPLC. A large portion of the B12 compound that moved like hydroxoB12 during cellulose acetate membrane electrophoresis using 0.5 N acetic acid might be identical with the unidentified B12 compound detected in the HPLC-bioautography.

Animals↗

PubMed2000

Reflex sympathetic dystrophy following transbrachial cardiac catheterization.

We experienced a rare case of complication by reflex sympathetic dystrophy (RSD) following transbrachial cardiac catheterization which may have been caused by poorly executed hemostasis using a hemostatic device. The symptoms of RSD markedly limited the patientOs daily work activities. Although the transbrachial approach is a useful procedure for cardiac catheterization, interventionalists should be aware that RSD may cause serious complications.

Aged↗

PubMed2000

Advances in genetic aspects of cystinuria.

Cystinuria has been clinically classified into three subtypes (I, II, and III) by Rosenberg and associates. In 1994, the SLC3A1 (rBAT) genes which is one of the genes responsible for cystinuria, was located on chromosome 2(2p21). However, it was demonstrated that rBAT is responsible only for Type I cystinuria. At present, 43 mutations, including 5 discovered in our laboratory, have been reported in the rBAT gene of patients with cystinuria. Recent studies suggest that the rBAT-encoded protein was not a transporter itself; rather, the protein represented a specific "guidance molecule" for a selected amino acid transporter. In 1999, the SLC7A9 (BAT1) gene was located on chromosome 19(19q13) by us and by a European group. It seemed that the BAT1 gene is responsible for non-Type I cystinuria and that its protein was a subunit linked to the rBAT protein via a disulfide bond. Mutational, structural, and functional analyses of the gene have been performed by several groups, including our laboratory. It is expected that the roles of these genes in cystinuria will be clarified further, and genetic diagnosis and therapy of patients with cystinuria may be facilitated in the future.

Amino Acid Transport Systems, Basic↗

PubMed1999

A novel mutation (Cys6Gly) in the Cu/Zn superoxide dismutase gene associated with rapidly progressive familial amyotrophic lateral sclerosis.

Autosomal-dominant familial amyotrophic lateral sclerosis (FALS) is associated with mutation in the gene that encodes Cu/Zn superoxide dismutase (SOD1). We identified a novel missense mutation of SOD-1 (Cys6Gly) in exon 1 in a Japanese woman and her family. The illness showed rapid progression similarly to the FALS with a mutation of Cys6Phe that was reported by Morita et al. (1996) (Morita, M., Aoki, M., Abe, K., Hasegawa, T., Sakuma, R., Onodera, Y., Ichikawa, N., Nishizawa, M. and Itoyama, Y., A novel two-base mutation in the Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan. Neurosci. Lett., 205 (1996) 79-82). Mutation of the cystein at amino acid 6 might be associated with the rapid progression of ALS.

Amyotrophic Lateral Sclerosis↗

PubMed1999

Identification of an amino acid transporter associated with the cystinuria-related type II membrane glycoprotein.

We identified an amino acid transporter that is associated with the cystinuria-related type II membrane glycoprotein, rBAT (related to b(0,+) amino acid transporter). The transporter designated BAT1 (b(0, +)-type amino acid transporter 1) from rat kidney was found to be structurally related to recently identified amino acid transporters for system L, system y(+)L, and system x(-)C, which are linked, via a disulfide bond, to the other type II membrane glycoprotein, 4F2hc (4F2 heavy chain). In the nonreducing condition, a 125-kDa band, which seems to correspond to the heterodimeric complex of BAT1 and rBAT, was detected in rat kidney with anti-BAT1 antibody. The band was shifted to 41 kDa in the reducing condition, confirming that BAT1 and rBAT are linked via a disulfide bond. The BAT1 and rBAT proteins were shown to be colocalized in the apical membrane of the renal proximal tubules where massive cystine transport had been proposed. When expressed in COS-7 cells with rBAT, but not with 4F2hc, BAT1 exhibited a Na(+)-independent transport of cystine as well as basic and neutral amino acids with the properties of system b(0,+). The results from the present investigation were used to establish a family of amino acid transporters associated with type II membrane glycoproteins.

ATP-Binding Cassette Transporters↗

PubMed1999

Clinicopathological study of an autopsy case with sensory-dominant polyradiculoneuropathy with antiganglioside antibodies.

A previously reported patient presenting sensory-dominant neuropathy with antiganglioside antibodies, bound preferentially to polysialogangliosides including GD1b, was autopsied. While axonal degeneration was predominant in the sural nerve, many demyelinated fibers were present in the spinal roots. Dorsal roots had undergone significant damage. These pathological findings were well correlated with the electrophysiological results showing decreased F-wave conduction velocities and conduction blocks in motor nerves and decreased or absent sensory action potentials in sensory nerves, with distribution of GD1b in nerve tissues such as dorsal root ganglia and paranodal myelin in the ventral and dorsal roots.

Aged↗