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M Tsuda

Publications and source records attributed to M Tsuda.

At least 145 records · Page 8Linked to original sources
PubMed1998

Alzheimer-associated presenilin-1 gene is induced in gerbil hippocampus after transient ischemia.

To investigate the biological roles of the presenilin-1 (PS-1) gene after neuronal injury, the changes of PS-1 mRNA expression in the gerbil hippocampus after transient ischemia were examined. From 1 day to 3 day-reperfusion after 5 min-ischemia, PS-1 mRNA was induced in the hippocampus compared with the sham-operated control. The cells which induced the PS-1 genes were neurons of CA3 and dentate gyrus, the region relatively resistant to ischemic stress. These findings suggest that the induction of PS-1 genes may be associated with some responses of neurons damaged by transient ischemia.

Alzheimer Disease↗
PubMed1998

Role of nitric oxide in the hypersusceptibility to pentylenetetrazole-induced seizure in diazepam-withdrawn mice.

The decrease in the seizure threshold for pentylenetetrazole in diazepam-withdrawn mice was not significantly affected by L-arginine (50 and 100 microg/mouse, i.c.v.), which did have an antiseizure effect in chronically vehicle-treated mice. Sodium nitroprusside (25 and 50 microg/mouse, i.c.v.) increased the seizure threshold for pentylenetetrazole in both diazepam-withdrawn mice and chronically vehicle-treated mice. In addition, the antiseizure effect of L-arginine was blocked by the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine (NOARG) and the NO scavenger, hemoglobin, while the effect of sodium nitroprusside was inhibited by hemoglobin, but not by NOARG, indicating that the antiseizure effect of L-arginine, but not that of sodium nitroprusside, is mediated by NO production resulting from the activation of NO synthase. Therefore, a decrease in the NO production via NO synthase may be involved in the hypersusceptibility to pentylenetetrazole during diazepam withdrawal.

Animals↗
PubMed1998

Use of a transposon-encoded site-specific resolution system for construction of large and defined deletion mutations in bacterial chromosome.

A class II transposon, Tn1722, encodes a site-specific resolution system, in which the resolvase (TnpR) efficiently catalyzes intramolecular recombination between the two directly oriented copies of the resolution site (res), leading to precise excision of the intervening DNA region. This property was exploited to develop the general strategies to introduce the large and defined deletion mutations into the bacterial chromosome. The Tn1722 res site was inserted into the plasmid carrying a cloned chromosomal fragment, and the resulting plasmid was integrated into a Tn1722-containing target chromosome by single crossover-mediated homologous recombination. The plasmid integrant carrying the two copies of the res site in the same orientation could efficiently excise the chromosomal region locating between the two res sites by means of the site-specific resolution system. Such site-specific deletion could be also detected by appropriate integration of the res-tnpR-containing plasmid into the chromosome in which another copy of the res site had been inserted through allelic exchange. This latter strategy was further modified to isolate the deletion mutations that were free of the resistance markers used for introduction of the res site and the res-tnpR block into the target chromosome. The deletion systems were applied to analyze the 103-kb pvd region of Pseudomonas aeruginosa PAO carrying most of the pyoverdin biosynthetic genes. Successful isolation of the mutation lacking more than a 100-kb fragment in the pvd region indicated that this region did not carry any essential genes.

Chromosome Deletion↗
PubMed1998

Upregulation of NMDA receptor subunit proteins in the cerebral cortex during diazepam withdrawal.

The present study investigated the changes in NMDA receptor subunit proteins in diazepam-withdrawn rat cerebral cortex, using Western blotting analysis. The protein levels of the NR1 and NR2B, but not NR2A, subunits were significantly increased in diazepam-withdrawn rats compared to those in control rats. Therefore, an increase in the NR1 and NR2B subunit proteins may be responsible for both the previously observed upregulation of [3H]dizocilpine binding in the cerebral cortex and the appearance of diazepam withdrawal signs.

Animals↗
PubMed1998

Region-specific changes in [3H]dizocilpine binding in diazepam-withdrawn rats.

In the present study, to clarify the role of the N-methyl-D-aspartate (NMDA) receptor in the appearance of diazepam withdrawal signs, the changes in [3H]dizocilpine binding in several brain regions from diazepam-withdrawn rats were investigated. Brain membranes were prepared 42-45 h after termination of diazepam treatment when maximal withdrawal signs were shown. The Bmax value for [3H]dizocilpine binding was significantly increased in cerebrocortical, but not hippocampal and cerebellar, tissues from diazepam-withdrawn rats, while the Kd value did not change in any group. Together with our previous finding that NMDA receptor antagonists potently suppress diazepam withdrawal signs, these results suggest that the upregulation of the NMDA receptor in the cerebral cortex may play an important role in the appearance of spontaneous withdrawal signs caused by discontinuation of chronic diazepam treatment.

Animals↗
PubMed1998

In vivo gene transfer into the adult mammalian central nervous system by continuous injection of plasmid DNA-cationic liposome complex.

Previously reported methods of liposome-mediated direct in vivo gene transfer have been inefficient, especially when performed with highly differentiated, quiescent cells of the adult mammalian central nervous system (CNS). We have therefore improved these procedures based upon a novel concept. Following continuous injection of plasmid DNA-cationic liposome complex which contained a reporter gene encoding E. coli beta-galactosidase into the striatum of adult rats, the expression of transgene was dramatically elevated without any adverse effects. This new technique may enable a wide application of liposome-mediated gene transfer technology not only to basic analysis of gene functions in the brain but also for clinical treatment of certain CNS disorders.

Animals↗
PubMed1998

Relationship between Joint National Committee-VI classification of hypertension and ambulatory blood pressure in patients with hypertension diagnosed by casual blood pressure.

BACKGROUND: White-coat hypertension has been diagnosed arbitrarily based on different criteria. In 1997, the Joint National Committee-VI (JNC-VI) reported a new classification of hypertension and strongly emphasized the importance of ambulatory blood pressure (ABP) monitoring. The report pronounced normal ABP values for the first time. HYPOTHESIS: The study's aim was to clarify the relationship between casual blood pressure (BP) and ABP of patients with essential hypertension in each stage of JNC-VI classification, and the prevalence of white-coat hypertension diagnosed by using JNC-VI normal ABP criteria. METHODS: Ambulatory blood pressure was monitored non-invasively in 232 patients with essential hypertension whose casual BP was > or = 140/90 mmHg. The patients were classified according to JNC-VI classification, and their casual BP was compared with ABP. The criterion of white-coat hypertension was defined as casual BP > or = 140/90 mmHg with normal ABP according to JNC-VI criteria (< 135/85 during daytime and < 120/75 during nighttime). RESULTS: Mean ABP increased as the stage advanced, and the differences between casual BP and ABP also increased. There were considerable overlaps in the distribution of ABP among stages. The prevalence of white-coat hypertension was 13% overall: 30% of the patients with isolated systolic hypertension, 19% of those in stage 1, 10% in stage 2, and 4% in stage 3. CONCLUSIONS: Classification of hypertension based on casual BP may not always correspond in severity to that based on ABP. Ambulatory blood pressure monitoring recommended by JNC-VI is very useful for the evaluation of hypertension to differentiate white-coat hypertension from true hypertension.

Adult↗
PubMed1998

Hypersusceptibility to DMCM-induced seizures during diazepam withdrawal in mice: evidence for upregulation of NMDA receptors.

The present study investigated the role of NMDA (N-methyl-D-aspartate) receptors in the hypersusceptibility to seizures induced by the benzodiazepine inverse agonist DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) during diazepam withdrawal in mice, using behavioral and biochemical approaches. The seizure threshold of DMCM was markedly decreased during diazepam withdrawal, reflecting withdrawal hyperexcitability in response to physical dependence. The decrease in the seizure threshold of DMCM in diazepam-withdrawn mice was inhibited by the non-competitive NMDA receptor antagonists MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate; 50 microg/kg, s.c.) and ifenprodil (20 mg/kg, i.p.). The effective doses of these compounds were lower than those required to prevent DMCM-induced seizures in chronically vehicle-treated mice. Since MK-801 and ifenprodil do not only bind to NMDA receptors but also to sigma receptors, the present study also investigated the effects of sigma receptor ligands. The decrease in the seizure threshold of DMCM in diazepam-withdrawn mice was not modified by the sigma receptor agonist, (+)-pentazocine (5 mg/kg, s.c.), or the sigma receptor antagonist, NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride; 5 mg/kg, i.p.). Furthermore, the latency to the expression of wild running induced by intracerebroventricular administration of NMDA (60 ng/mouse) was also significantly lower in diazepam-withdrawn mice than in vehicle-treated control mice. On the other hand, there was no difference in the spermidine concentration between vehicle-treated control and diazepam-withdrawn mice. In a receptor binding experiment, the Bmax value for [3H]-MK-801 binding was significantly increased in cerebrocortical tissues from diazepam-withdrawn mice, while the Kd value did not change in either group. However, the acute addition of a high concentration of diazepam (10 and 100 microM) in vitro did not alter [3H]-MK-801 binding in cerebrocortical membrane preparations. The behavioral experiments suggest that NMDA receptor antagonists may suppress benzodiazepine withdrawal responses, while the biochemical study reveals upregulation of the NMDA receptor, which may play an important role in the hypersusceptibility to DMCM-induced seizure in diazepam-withdrawn mice.

Animals↗
PubMed1998

A novel mutation at a probable heme-binding ligand in neutrophil cytochrome b558 in atypical X-linked chronic granulomatous disease.

A membrane-bound cytochrome b558, a heterodimer consisting of gp91-phox and p22-phox, is a critical component of the superoxide (O2-)-generating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. Chronic granulomatous disease (CGD) is characterized by recurrent bacterial infection caused by a defect of the oxidase. Both subunits are absent from phagocytes in typical X-linked recessive CGD patients who are primarily defective in gp91-phox. We report here an atypical case of X-linked CGD in which neutrophils showed a complete absence of O2--forming NADPH oxidase activity, but a small amount (about 10% of control) of both subunits was detected by immunoblot analysis. Spectrophotometric studies of the neutrophils with a recently developed sensitive method gave no evidence for the heme spectrum in the cytochrome b558, of this CGD. Reverse transcription/polymerase chain reaction and sequence analysis revealed a C to T transition replacing histidine at amino acid position 101 (His101) by tyrosine in gp91-phox. These results provide evidence that His101 of gp91-phox is the one of the heme-binding ligands of cytochrome b558.

Adolescent↗
PubMed1998

Subsensitivity to mitochondrial diazepam binding inhibitor receptor agonist FGIN-1-27-induced antiseizure effect in diazepam-withdrawn mice.

We investigated the role of the mitochondrial diazepam binding inhibitor receptor (MDR) in diazepam-withdrawal seizure. In chronically vehicle-treated mice, the potent and selective MDR agonist FGIN-1-27 (N,N-di-n-hexyl 2-(4-fluorophenyl)indole-3-acetamide: 30 microg/mouse, i.c.v.) markedly increased the threshold for pentylenetetrazole (PTZ)-induced seizure. The antiseizure effect of FGIN-1-27 was blocked by pretreatment with the selective MDR antagonist PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxa mide). In chronically diazepam-treated mice, the seizure threshold of PTZ was decreased during diazepam withdrawal, indicating withdrawal hyperexcitability. Interestingly, FGIN-1-27 (30 microg/mouse, i.c.v.) failed to increase the seizure threshold of PTZ in diazepam-withdrawn mice, in contrast to its effect in chronically vehicle-treated mice. These findings suggest that the sensitivity of MDR-mediated pathways in the brain may be decreased during diazepam withdrawal.

Animals↗
PubMed1998

Expression of an ADP-ribosylation factor like gene, ARF4L, is induced after transient forebrain ischemia in the gerbil.

To elucidate the molecular mechanisms underlying post-ischemic phenomena including delayed neuronal death, we screened for genes which were induced in the hippocampus after transient global ischemia in the Mongolian gerbil by a differential display method, and cloned a gerbil homologue of human ADP-ribosylation factor 4L (ARF4L). Although the physiological roles of ARF4L are unknown, it is likely that ARF4L participates in vesicle transport between the endoplasmic reticulum (ER) and Golgi complex as it contains a GTP binding site, myristoylation site and coatmer binding motif (KKXX). In situ hybridization analysis indicated that the expression of ARF4L mRNA was elevated in neurons of the dentate gyrus (DG) and CA1 regions. In DG, the signals were detected 3 h after ischemia and peaked at 6 h with subsequent gradual reduction. On the other hand, in the CA1 region where cell death occurs in this model, ARF4L mRNA was slightly detected from 1 to 2 days after ischemia but was absent after 3 days. Other vesicle transport-related genes such as ARF1, ARL4 and beta-COP were also induced after 5-min ischemia, suggesting that vesicle transport was activated in hippocampal neurons after ischemic stress. To determine the cause of the induction of ARF4L gene expression after transient ischemia, we examined the changes in ARF4L mRNA expression in HEK 293 cells under hypoxic conditions compared with HSP70. The expression of ARF4L mRNA was elevated at 12 h after hypoxia exposure, similarly to HSP70. These results will help to elucidate the association of upregulation of vesicle transport systems including ARF4L and stress responses of neurons after transient ischemia.

ADP-Ribosylation Factor 1↗
PubMed1998

Attenuation of cell death mediated by membrane depolarization different from that by exogenous BDNF in cultured mouse cerebellar granule cells.

Membrane depolarization accompanying calcium (Ca2+) influx into neurons is thought to play an essential role in controlling the survival and death of cultured mouse cerebellar granule cells (CGCs). In this study, we sequentially controlled the survival and death of CGCs in culture and monitored the expression of several kinds of genes including brain-derived neurotrophic factor (BDNF) gene. Deprivation and subsequent induction of membrane depolarization by lowering and re-elevating the extracellular concentration of potassium chloride, respectively, led to death of CGCs and then to an attenuation of the death process depending upon the Ca2+ influx into CGCs through voltage-dependent calcium channels (VDCCs). De novo protein synthesis was critical for attenuating the death of non-depolarized CGCs. Accompanying this attenuation was an activation of c-fos and BDNF genes and an inactivation of c-jun and neurotrophin-3 (NT-3) genes. The attenuation of cell death mediated by exogenous BDNF was only partial compared to that by membrane depolarization, suggesting that not only BDNF but also other factors could be involved in the membrane depolarization-mediated attenuation of death of CGCs. In good agreement with this observation, the mode of activation of c-fos, c-jun, BDNF and NT-3 genes induced by exogenous BDNF was different from that induced by membrane depolarization. Thus, membrane depolarization effectively attenuates the death of non-depolarized CGCs, the mode of which seems to be different from that mediated by BDNF alone.

Animals↗
PubMed1998

Three new manzamine congeners from amphimedon sponge

Three new manzamine congeners (1-3) have been isolated from the Okinawan marine sponge Amphimedon sp., and the structures, including relative stereochemistries, were elucidated on the basis of spectroscopic data. Absolute configuration at C-16 of 1 was determined by modified Mosher's method.

Journal Article↗
PubMed1998

Seasonal changes in phytohemagglutinin-induced cytokine synthesis by peripheral blood lymphocytes of patients with seasonal allergic rhinitis due to Japanese cedar pollens.

We investigated the seasonal changes in non-specific stimulation-induced cytokine production by peripheral blood mononuclear cells (PBMCs) in patients with seasonal allergic rhinitis due to Japanese cedar pollen. This study included 16 non-allergic healthy adult volunteers and 115 patients with detectable levels of Japanese cedar pollen-specific IgE in their serum. The 115 patients were divided into five groups, an asymptomatic group (specific IgE was positive but there were no nasal symptoms), a medication group (typical symptoms of Japanese cedar pollinosis and treated with antihistamine tablets), a good-IT group (responded well to immunotherapy), a poor-IT group (responded poorly to immunotherapy) and a cure group (no symptoms after discontinuation of immunotherapy). PBMCs (1.0 x 10(6) cells/ml) were collected before and during the cedar pollen season in 1998, and were cultured for 24 h in the presence of 10 micrograms/ml phytohemagglutinin. The concentrations of IL-4, IL-5 and IFN-gamma in the culture supernatants were measured by an enzyme-linked immunosorbent assay. None of the levels of IL-4, IL-5 and IFN-gamma synthesized by PBMCs in the asymptomatic group, medication group, good-IT group, poor-IT group or cure group were significantly different from those in the non-atopic group. In the medication group, the synthesis of TH2-type cytokines (both IL-4 and IL-5), but not of TH1-type cytokine (IFN-gamma) was significantly increased during the pollen season compared with before the pollen season, whereas in the non-atopic group, the synthesis of IL-4, IL-5 and IFN-gamma did not differ significantly before and during the pollen season. The synthesis of both IL-4 and IL-5 was significantly increased during the pollen season in the poor-IT group, whereas the synthesis of IL-4 and IL-5 was not increased during the pollen season in the good-IT or cure groups. In conclusion, our study demonstrates that T-cell reactivity to non-specific stimulation outside of the pollen season did not differ between the patients with seasonal allergic rhinitis and non-atopic individuals, that T-cells in patients with seasonal allergic rhinitis are affected or primed by the natural pollen exposure to synthesize TH2-type cytokines even in response to non-specific stimulation, and that successful immunotherapy could decrease the natural pollen exposure-primed hyperreactivity of TH2 cells to non-specific stimulants.

Adult↗
PubMed1998

Relationships between the synthesis of N-nitrosodimethylamine and immune responses to chronic infection with the carcinogenic parasite, Opisthorchis viverrini, in men.

This study investigated the relationship between immune responses to infection with the liver fluke, Opisthorchis viverrini, and the synthesis of the carcinogen, N-nitrosodimethylamine (NDMA) in humans. It also examined associations between synthesis of nitric oxide (NO) and nitrosation of amines, in vivo. Antibody and T cell responses to fluke antigens and post-alcohol urinary NDMA excretion were assessed among three groups of 40-50 men with no, moderate and heavy liver fluke infection. Markers of NO synthesis (nitrate, nitrite) and nitrosation (nitrosamino acids) were also measured in biological fluids. Assessments were carried out under controlled conditions which minimised intake of exogenous nitrate and nitrite and were carried out at two time points, namely before and 4 months after elimination of the infection with praziquantel treatment. No statistically significant variation was observed in the amount of NDMA excreted between the 3 groups. However, during active infection, a strong negative association was observed between in vitro lymphoproliferative responses to some liver fluke antigens and NDMA excretion. After treatment this association was reduced. Multivariate statistical models revealed a highly significant relationship between NDMA levels and urinary nitrate, stimulation indices for two T cell responses to two parasite antigens (MW 37 kDa and 110 kDa) and gall bladder dimensions. NDMA levels after treatment were best described by the ratio between parasite-specific IgG2 and IgE, background levels of T cell proliferation, a urinary marker of nitrosation (N-nitrosothioproline) and usual level of alcohol consumption. These results suggest that individual background immunologic activity, parasite-specific responses and/or parasite products and NO synthesis are important determinants of endogenous generation of nitrosamines in O. viverrini-infected humans.

Adult↗
PubMed1998

An enzyme immune assay for serum anti-acetaldehyde adduct antibody using low-density lipoprotein adduct and its significance in alcoholic liver injury.

An acetaldehyde (AcH) adduct was prepared using rabbit low-density lipoprotein as carrier proteins. An antibody against this adduct was raised in Watanabe heritable hyperlipidemic rabbits and cross-reacted with human low-density lipoprotein and bovine serum albumin adducts. Using this antibody, serum anti-AcH-adduct antibody levels were measured by a direct ELISA method in 56 Japanese adults (healthy adults and patients with nonalcoholic gastrointestinal diseases, alcoholic liver injury, or alcoholic pancreatitis). The antibody level (mean +/- SD) was 22 +/- 10 microg/ml in healthy adults, 22 +/- 11 microg/ml in nonalcoholic gastrointestinal diseases, and 16 +/- 13 microg/ml in alcoholic pancreatitis. These antibody levels tended to increase with the progression of alcoholic liver injury, starting from fatty liver via hepatitis to cirrhosis, 29 +/- 24 microg/ml in fatty liver, 35 +/- 29 microg/ml in alcoholic hepatitis, and 46 +/- 54 microg/ml in alcoholic cirrhosis. The antibody level in patients taking 100 g or more of ethanol per day tended to be higher, compared with those in people taking less ethanol. A follow-up observation revealed that alcohol abstinence after hospitalization raised serum anti-AcH-adduct antibody level in some patients and kept it constantly low in other patients. The immunohistochemical study using the anti-AcH-adduct antibody revealed the presence of adduct-like substance in hepatocytes of liver biopsy specimens obtained from patients with alcoholic liver disease. The results indicate that the anti-AcH-adduct antibody may be associated with the progress of alcoholic liver diseases.

Acetaldehyde↗
PubMed1998

Spectrophotometric determination of neutrophil cytochrome b558 of chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disease characterized clinically by severe recurrent bacterial infections from infancy. This disease is a disorder of the formation of superoxide (O2-) by the neutrophil NADPH oxidase system, mostly due to defects in cytochrome b558 (cyt b558), which is one of the oxidase components. Diagnosis of CGD has been performed by the assay of the O2- forming activity, immunological determination of defects in the oxidase components, and or spectrophotometry of cyt b558. However, spectrophotometric analysis of the b-type heme is difficult with small amounts of blood from infant CGD patients, as the limited amounts of neutrophils are contaminated with a relatively high ratio of hemoglobin (Hb) that interferes with the heme spectrum of cyt b558. This report presents an accurate method for the spectrophotometric analysis of cyt b558 in a small amount of CGD neutrophils that were treated with CO gas in a safe procedure instead of the previously reported CO-bubbling method. METHODS AND RESULTS: The difference of the reduced minus oxidized cyt b558 spectrum was measured under no interference from oxy Hb at the alpha and beta bands and differentiated as d[delta A]/d lambda (lambda = wavelength) to obtain further evidence for the defects of the cyt b558 heme spectrum. The interference from CO-insensitive met Hb was eliminated by subtracting the absorption peak at the Soret (gamma) band of the contaminating met Hb, which was estimated from the CO-treated and untreated spectra of the same, hemolyzed sample. CONCLUSIONS: This spectrophotometric method is feasible for the determination of abnormality and heme content of cyt b558 with a small amount of CGD neutrophils in 10-20 mL of blood even in the presence of contaminating Hb.

Cytochrome b Group↗