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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 415 records · Page 23Linked to original sources
PubMed1997

FK506 prevents induction of rat experimental autoimmune myasthenia gravis.

Myasthenia gravis (MG) is an organ-specific autoimmune disease attacking nicotinic acetylcholine receptors (AChR) of the neuromuscular junction. Autoantibody production is regulated by autoimmune helper T cells that are specific to AChR. Therefore the suppression of autoimmune T cell activity could reduce myasthenic symptoms. Amongst immunomodulatory therapies aimed at T cells, we studied the therapeutic effect of FK506 as a T cell-specific immunosuppressive agent. Rats in which experimental autoimmune myasthenia gravis (EAMG) was induced by immunization with synthetic peptide of human AChR alpha-subunit residues 125-147 (H alpha 125-147) were treated daily with FK506 (1 mg/kg). FK506 prevented the reduction in amplitude of miniature endplate potential (MEPP) which was induced by H alpha 125-147 immunization. FK506 also suppressed anti-H alpha 125-147 and anti-rat AChR antibody production accompanied by a decrease in the antigen-specific T cell response against H alpha 125-147. These findings indicate that FK506 prevents induction of rat EAMG evoked by immunizing T cells against H alpha 125-147.

Amino Acid Sequence↗
PubMed1997

Use of polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis to detect a point mutation in the catalase-peroxidase gene (katG) of Mycobacterium tuberculosis.

We have previously reported that a significant percentage (44%) of isoniazid-resistant Mycobacterium tuberculosis strains carry an arginine to leucine mutation in codon 463 (R463L) in the catalase-peroxidase gene (katG). For the current study, we compared the utility of one mutation screening method, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, with a reference method, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), to detect this mutation. The PCR-SSCP method detects mutations by electrophoretic mobility shifts of single-stranded DNA in nondenaturing polyacrylamide gels. The RFLP method detects a loss in an Mspl restriction site which occurs when the R463L is present. Eighty one M. tuberculosis strains, including the wild type strain H37Rv, with isoniazid susceptibility in the range < 0.12 to > 32 micrograms ml-1 were evaluated. The results for the PCR-SSCP method were in complete agreement with the PCR-Mspl RFLP reference method. Of 81 M. tuberculosis strains analysed, 13 showed mobility shifts by the PCR-SSCP method and all of those strains carried the R463L as detected by the PCR-Mspl RFLP method. All of the remaining 54 strains had PCR-SSCP and PCR-Mspl RFLP results identical to the wild type (R463) M. tuberculosis strain, H37Rv. It is concluded that the described PCR-SSCP is a reliable method for screening M. tuberculosis strains for the katG R463L mutation.

Bacterial Proteins↗
PubMed1997

Comparison of 99mTc-Technegas SPECT with 133Xe dynamic SPECT in pulmonary emphysema.

This study was undertaken to compare axial images of 99mTc-Technegas SPECT (Technegas) with those of 133Xe gas dynamic SPECT in patients with pulmonary emphysema. There were 20 patients, 19 males and 1 female. All patients except one ex-smoker were heavy smokers with a mean age of 68.1 years. For Technegas scintigraphy, the patients inhaled 505 MBq 99mTc-Technegas in several tidal volume breaths in the supine position without breath holding. For 133Xe gas scintigraphy, the patients inhaled 370 MBq 133Xe gas. 133Xe gas dynamic SPECT was performed in the equilibrium phase for the last minute of the 3 minute inhalation in a closed circuit, and in the washout phase for 6 minutes of inhalation in a semi-closed circuit, by means of a gamma camera with dual detectors (Picker model Prism 2000). Abnormal findings included heterogeneity, defects and hot spots on Technegas images and on retention images taken 3 minutes after 133Xe gas washout. In 2 of 20 patients, the degree of abnormal findings on Technegas images depended on the area of 133Xe gas retention in the washout phase. In 3 patients, the degree of abnormal findings on both Technegas SPECT and 133Xe gas dynamic SPECT images were equivalent. In the remaining 15 patients, more detailed findings and a greater area were shown by Technegas SPECT than 133Xe gas dynamic SPECT. We conclude that in patients with pulmonary emphysema Technegas SPECT can demonstrate ventilation impairment more easily than 133Xe gas dynamic SPECT.

Aged↗
PubMed1997

Assessment of technetium-99m Technegas scintigraphy for ventilatory impairment in pulmonary emphysema: comparison of planar and SPECT images.

Pulmonary emphysema can be diagnosed easily by X-ray CT (CT) as a low attenuation area. Recently Tc-99m-Technegas (Technegas) has been used for ventilation scintigraphy. The present study was undertaken to assess the usefulness of planar and SPECT images by using Technegas scintigraphy in patients with pulmonary emphysema. Technegas scintigraphy, CT and pulmonary function tests were performed in 20 patients (males, age 32-78 years). We classified the findings of Technegas images into 4 grades. Comparing planar and SPECT images of Technegas, more detailed findings were shown by SPECT than by planar images in mild cases (6 cases, 30%). In more severe cases, findings of SPECT and planar images were equivalent (14 cases, 70%). The degree of abnormal findings obtained by SPECT was equivalent to that obtained by CT in severe cases (6 cases, 30%). SPECT should be excluded in advanced stages as indicated by planar images.

Adult↗
PubMed1997

Hypnotic and hypothermic action of daytime-administered melatonin.

Six healthy male volunteers (average age = 22.5 years) received orally melatonin (MLT; 3 mg or 9 mg) or placebo at 0930 hours in a randomized, single-blind, cross-over study. Both doses of exogenously administered melatonin (ex-MLT) induced transient, significant suppression of core body temperature (BT) compared to the placebo condition. There was no significant difference in the degree of BT suppression among the two MLT conditions in spite of significantly higher levels of serum MLT with the close of 9 mg, suggesting that there may be a threshold level of ex-MLT inducing the hypothermic action. Daytime administered ex-MLT also induced a significant sleep-inducing effect only in the 9 mg condition, while 3 mg ex-MLT failed to produce statistical significance. These findings suggest that the sleep-inducing action of ex-MLT occurs only at relatively high doses, and this action is probably not due to its BT lowering action. The present study led us to assume that ex-MLT produce its therapeutic effect for circadian rhythm sleep disorders through induction of circadian phase-shifting preceded by an acute, transient hypothermic action rather than light entrainment after setting sleep time by induction of sleep propensity.

Adult↗
PubMed1997

What remaining questions regarding Helicobacter pylori and associated diseases should be addressed by future research? View from the Far East.

Based on the findings of several epidemiological studies, it is believed that Helicobacter pylori infection is closely associated with gastric cancer. Because some abnormalities, such as severe inflammation in the gastric mucosa, impaired secretion of vitamin C, and increased gastric cell proliferation, improve after cure of the infection, anti-H. pylori therapy may reduce the incidence of gastric cancer. In Japan, the odds ratios for the development of atrophic gastritis and gastric cancer in H. pylori-positive patients are not as high as those reported in Europe and the United States. These findings suggest that factors other than H. pylori may exert a considerable influence on the development of atrophic gastritis and gastric cancer in Japan. It is not known whether atrophy and intestinal metaplasia, possible precursors of gastric cancer, are reversible. H. pylori infection is associated with a "gastritis, intestinal metaplasia, and gastric cancer sequence," but it remains obscure whether the infection is directly associated with the development of gastric cancer. We do not know which age group of patients should be given anti-H. pylori therapy for the prevention of gastric cancer. To elucidate whether the eradication of H. pylori can prevent gastric cancer, a Japanese intervention trial is now in progress.

Clinical Trials as Topic↗
PubMed1997

Effect on an iron-chelator on ascorbate-induced cytotoxicity.

We investigated the effect of deferoxamine mesylate (DFO), an iron chelator, to test whether ascorbate-induced cytotoxicity is due to iron-catalyzed oxidation. Exposing human promyelocytic leukemic HL-60 cells to either sodium ascorbate or ascorbic acid for 1 h resulted in the progressive production of apoptotic cells characterized by cell shrinkage, as well as nuclear and internucleosomal DNA fragmentation. The addition of micromolar to millimolar concentrations of DFO during the 1-h exposure did not inhibit, but rather enhanced the ascorbate-induced apoptosis in both regular and serum-free RPMI1640 medium. However, a higher concentration of serum significantly inhibited the ascorbate-induced cytotoxicity. In contrast, the cytotoxic activity of ascorbate against T98G human glioblastoma cells was enhanced or reduced by micromolar and millimolar concentrations of DFO, respectively. Ascorbate significantly increased the oxidation potential in the culture medium, and the pro-oxidant action of ascorbate was further augmented by the presence of the cells. DFO did not significantly affect the ascorbyl radical intensity and only slightly reduced the ascorbate-elevated oxidation potential. These data demonstrated that ascorbate can induce cytotoxicity even in iron-deficient medium.

Apoptosis↗
PubMed1997

Effects of YM-43611, a novel dopamine D2-like receptor antagonist, on immediate early gene expression in the rat forebrain.

The pharmacological characteristics of two benzamides, YM-43611, a potent and selective dopamine D3 and D4 antagonist, and YM-09151-2 (nemonapride), were compared with two reference antipsychotic agents, haloperidol and clozapine, in terms of modification of c-fos and related gene expression in the rat forebrain. After subcutaneous injection of YM-43611 (1 or 5 mg/kg), nemonapride (4 mg/kg), haloperidol (1 mg/kg), or clozapine (25 mg/kg), Fos immunocytochemistry was employed, and the distributions of Fos-like immunoreactive neurons were compared. As was the case for the two reference antipsychotics, the two benzamides enhanced c-Fos immunoreactivity in a number of forebrain regions. Specifically, like clozapine and nemonapride, YM-43611 significantly increased the number of immunoreactive cells in the nucleus accumbens shell and islands of Calleja. In contrast to clozapine and nemonapride, YM-43611 did not increase c-fos expression in the medial prefrontal cortex. Haloperidol and nemonapride elevated the number of positive cells in the striatum and nucleus accumbens core, whereas clozapine and YM-43611 did not. Clozapine increased the number of Fos-like immunoreactive cells in the lateral septal nucleus and the diagonal band nucleus, but YM-43611, nemonapride, and haloperidol did not. The present findings demonstrate that in comparison with three other drugs, YM-43611 has restricted effects on c-fos expression in the rat forebrain and is active primarily in the shell region of the nucleus accumbens and the islands of Calleja. The ability of YM-43611 to block D3 and D4 receptors may contribute to its unique actions on Fos induction.

Animals↗
PubMed1997

Limitation of stunning in dog myocardium by nucleoside and nucleotide mixture, OG-VI.

OG-VI is a solution composed of 30 mM inosine, 30 mM sodium 5'-guanylate, 30 mM cytidine, 22.5 mM uridine, and 7.5 mM thymidine, expecting to use for total parenteral nutrition. We examined the effect of OG-VI on myocardial contractile dysfunction during reperfusion after ischemia (myocardial stunning) in dogs. Pentobarbital-anesthetized dogs were subjected to 20-min left anterior descending coronary artery ligation followed by 30-min reperfusion. Saline, OG-VI or its constituents [inosine and sodium 5'-guanylate mixture (IG), and cytidine, uridine, and thymidine mixture (CUT)], or 5-amino-4-imidazole carboxamide riboside (AICAr) was infused at 0.1 mL.kg-1.min-1, starting 30 min before the ischemia. The contractile function was determined by ultrasonometry and assessed as % segment shortening (%SS). %SS was markedly decreased by ischemia, and returned toward pre-ischemic level after reperfusion, although the recovery was incomplete. The %SS was almost completely recovered by OG-VI and IG, and to a lesser extent by AICAr; CUT was ineffective. In the presence of 1 mg.kg-1 of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, a selective adenosine A1 receptor antagonist), cardioprotective effect of OG-VI on stunned myocardium was still observed. In conclusion, infusion of OG-VI improved myocardial contractile dysfunction in stunned myocardium. This effect was more potent than its constituents and AICAr. Adenosine A1 receptors are not involved in the mechanism.

Adenosine Triphosphate↗
PubMed1997

Preparation of human whole lungs inflated and fixed for radiologic-pathologic correlation.

RATIONALE AND OBJECTIVES: The authors evaluated a modified method of lung inflation and fixation for radiologic-pathologic correlation of lung disease. METHODS: Fifty-five whole human lungs obtained at autopsy were examined. Fifty lungs were cannulated via the main bronchus and distended with 20% formalin. The cannula was clamped for 15 minutes, 30 minutes, 2 hours, 2 days, 4 days, or 6 days. Then the formalin was expelled with air at a pressure of 10 cm H2O. The lung was fixed with a mixture of polyethylene glycol 400, 95% ethyl alcohol, 40% formalin, and water. In the five lungs that were not cannulated, the formalin was expelled manually. RESULTS: The degree of inflation of 46 cannulated specimens was rated as good in 42, moderate in four, and poor in nine. Histologic preservation was not evaluated in 23 of 55 specimens because of postmortem autolysis. It was rated as good or moderate in 29 specimens. Both inflation and staining were rated as good in 21 specimens. CONCLUSION: This modified method of preparation of inflated, fixed lung provides good histologic preservation and radiographic appearance of lung.

Cadaver↗
PubMed1997

Comparison of ranitidine and lansoprazole in short-term low-dose triple therapy for Helicobacter pylori infection.

AIM: To evaluate the efficacy and safety of two 1-week low-dose triple-therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection. 99 patients with H. pylori infection were treated with either lansoprazole or ranitidine used together with clarithromycin and metronidazole. METHODS: The drug combination and administration periods in the proton pump inhibitor group were lansoprazole 30 mg o.m., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d., all given for 7 days (LCM group). The ranitidine group received ranitidine 150 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d. also for 7 days (RCM group). The presence or absence of H. pylori was determined from gastric biopsy specimens taken from both the antrum and the body, by smear, culture and tissue section (Giemsa stain). Cure was defined as failure to find evidence of H. pylori infection 4 weeks after antimicrobial therapy had ended. RESULTS: The cure of H. pylori infection was 88% in the LCM group (44 of 50; 95% confidence interval (CI) = 79-97%) and 92% in the RCM group (45 of 49; 95% CI = 84-99%). The incidence of adverse events was 16% and 18% for the two groups, respectively. CONCLUSIONS: No significant differences in cure rate and safety profiles were noted between the two regimens, suggesting that moderate acid inhibition using an H2-blocker is sufficient to achieve optimal H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95.

BACKGROUND: The human homologue of the Drosophila discs large tumour suppressor protein (hDLG) and closely related proteins such as postsynaptic density protein 95 kDa (PSD-95) are associated with N-methyl-D-aspartate receptors (NMDA-R) and Shaker-type K+ channels, and are thought to be involved in their clustering. RESULTS: We have identified a protein named DAP-1 that binds to the guanylate kinase-like domains of hDLG and PSD-95. DAP-1 was found to associate with hDLG, PSD-95, NMDA-R and adenomatous polyposis coli protein (APC). Furthermore, we found that DAP-1 is specifically expressed in the brain and colocalizes with PSD-95 and APC in mouse cerebellum. We also found that DAP-1 is colocalized with PSD-95 and NMDA-R at the synapses in cultured rat hippocampal neurons. CONCLUSION: Our findings suggest that DAP-1 may play several roles in the molecular organization of synapses and neuronal cell signalling by interacting with hDLG and PSD-95, which in turn are associated with receptors, ion channels and APC.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Surgical management of Mycobacterium avium complex disease.

Between July 1991 and October 1996, eight patients with Mycobacterium avium complex (MAC) underwent pulmonary resection in our department. There was equal distribution of men women. The length of the preoperative period averaged 8.1 months (range: 1 to 30 months). Surgical resection was complete, consisting of lobectomy in 4 patients, lobectomy with partial resection in 2, segmentectomy in 1, and segmentectomy with partial resection in 1. There were no major complications postoperatively. No patients had positive sputum culture with MAC just after operation; however, one patient had positive sputum culture 6 months after operation. Our results show the good outcome of resectional surgery for MAC in properly selected patients, who should be operated as early as possible.

Female↗
PubMed1997

Citrus auraptene inhibits chemically induced colonic aberrant crypt foci in male F344 rats.

The modifying effect of dietary administration of auraptene isolated from the peel of citrus fruit (Citrus natsudaidai Hayata) on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce ACF. They also received diets containing 100 or 500 p.p.m. auraptene for 5 weeks, starting 1 week before the first dose of AOM. At termination of the study (week 5) dietary administration of auraptene caused a significant reduction in the frequency of ACF in a dose-dependent manner (P < 0.05). Feeding of auraptene suppressed expression of cell proliferation biomarkers (5-bromo-2'-deoxyuridine labeling-index, ornithine decarboxylase activity, polyamine content and number of silver stained nucleolar organizer region protein particles) in the colonic mucosa and the occurrence of micronuclei caused by AOM. Also, auraptene increased the activities of phase II enzymes (glutathione S-transferase and quinone reductase) in the liver and colon. These findings might suggest that inhibition of AOM-induced ACF may be associated, in part, with increased activity of phase II enzymes in the liver and colon and suppression of cell proliferation in the colonic mucosa.

Animals↗
PubMed1997

Modulation of N-methyl-N-amylnitrosamine-induced rat oesophageal tumourigenesis by dietary feeding of diosmin and hesperidin, both alone and in combination.

The modifying effects of flavonoids diosmin and hesperidin during the initiation and post-initiation phases of oesophageal carcinogenesis initiated with N-methyl-N-amylnitrosamine (MNAN) were investigated in male Wistar rats. At 7 weeks of age, all animals except those treated each test chemical alone and control groups were given weekly intraperitoneal injections of MNAN (12.5 mg/kg body weight/injection) for 12 weeks to induce oesophageal neoplasms. For examining the modifying effects of 'initiation' treatment of test compounds, groups of animals were fed the diets containing 1000 ppm diosmin and 1000 ppm hesperidin, and the diet containing both compounds (900 ppm diosmin and 100 ppm hesperidin) for 13 weeks, starting 7 days before the MNAN dosing and then switched to the basal diet. For examining the modifying effects of 'post-initiation' treatment of these compounds, the groups given MNAN and a basal diet were switched to the experimental diets containing diosmin, hesperidin or diosmin combined with hesperidin at 1 week after the stop of MNAN injection, and maintained on these diets for 7 weeks. The other groups consisted of rats given test compounds alone or untreated rats. All animals were necropsied at the termination of the study (week 20) to determine the incidences of oesophageal neoplasms and preneoplasms, blood polyamine levels, and cell proliferation activity estimated by 5-bromodeoxyuridine (BrdU)-labelling index and by morphometric analysis of silver-stained nucleolar organizer regions' protein (AgNORs). A number of oesophageal neoplasms developed in rats treated with MNAN alone (75% and 100% incidences of carcinoma and papilloma, respectively). 'Initiation' feeding of diosmin significantly decreased the incidence of squamous cell carcinoma (P < 0.05). Also, 'initiation feeding' of both compounds singly or in combination caused a significant reduction in the multiplicities of oesophageal carcinoma and papilloma (diosmin, 78 and 58% reduction; hesperidin, 70 and 50% reduction; and the combination regimen, 70 and 30% reduction, P < 0.005). 'Post-initiation' feeding slightly decreased the multiplicities of these oesophageal neoplasms. Also, these dietary regimens reduced the multiplicities of preneoplastic lesions (hyperplasia and severe dysplasia; P < 0.05). There were no pathological alterations in rats treated with both compounds alone or the combined regimen alone or those in an untreated control group. Similarly, feeding of these compounds significantly decreased the expression of cell proliferation biomarkers (BrdU-labelling index and AgNORs number) of the non-lesional oesophageal epithelium (P < 0.05). Blood polyamine concentrations were also lowered in rats given the carcinogen and test compounds, both alone and in combination, when compared with those of rats given MNAN alone (P < 0.05). These findings suggest that diosmin and hesperidin supplementation, individually or in combination, is effective in inhibiting the development of oesophageal cancer induced by MNAN when given during the initiation phase, and such inhibition might be related to suppression of increased cell proliferation caused by MNAN in the oesophageal mucosa.

Administration, Oral↗
PubMed1997

A xanthine oxidase inhibitor 1'-acetoxychavicol acetate inhibits azoxymethane-induced colonic aberrant crypt foci in rats.

The modifying effect of dietary administration of a xanthine oxidase inhibitor 1'-acetoxychavicol acetate (ACA) present in an edible plant Languas galanga in Thailand on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce colonic ACF. They were fed the diets containing 100 or 200 ppm ACA for 5 weeks, starting 1 week before the first dosing of AOM. At the termination of the study (week 5), AOM induced 118 +/- 28 ACF/colon. Dietary administration of ACA caused significant reduction in the frequency of ACF (41% inhibition by 100 ppm ACA feeding and 37% inhibition by 200 ppm ACA feeding, P<0.01). Such inhibition might be associated with suppression of the proliferation biomarkers' expression such as ornithine decarboxylase activity in the colonic mucosa, number of silver-stained nucleolar organizer regions' protein in the colonic mucosal cell nuclei and blood polyamine content. These results indicate that ACA could inhibit the development of AOM-induced ACF through its suppression of cell proliferation in the colonic mucosa and ACA might be a possible chemopreventive agent against colon tumourigenesis.

Animals↗
PubMed1997

Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin.

The modulating effects of dietary feeding of two flavonoids, diosmin and hesperidin, both alone and in combination, during the initiation and post-initiation phases on colon carcinogenesis initiated with azoxymethane (AOM), were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induced colon neoplasms. Rats were fed the diets containing diosmin (1000 ppm), hesperidin (1000 ppm) or diosmin (900 ppm) + hesperidin (100 ppm) for 5 weeks (initiation treatment) or 28 weeks (post-initiation treatment). The others contained the groups of rats treated with diosmin, hesperidin alone or in combination, and untreated. At the end of the study (32 weeks), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM together with, or followed by, a diet containing diosmin or hesperidin were significantly smaller than those of rats given AOM alone (P <0.001). The combination regimen during the initiation and post-initiation stages also inhibited the development of colonic neoplasms, but the tumor data did not indicate any beneficial effect of diosmin and hesperidin administered together as compared with when these agents were given individually. In addition, feeding of diosmin and hesperidin, both alone and in combination, significantly inhibited the development of aberrant crypt foci. As for cell proliferation biomarkers, dietary exposure of diosmin and hesperidin significantly decreased the 5'-bromodeoxyuridine-labeling index and argyrophilic nuclear organizer region's number in crypt cells, colonic mucosal ornithine decarboxylase activity, and polyamine levels in the blood. These results indicate that diosmin and hesperidin, both alone and in combination, act as a chemopreventive agent against colon carcinogenesis, and such effects may be partly due to suppression of cell proliferation in the colonic crypts, although precise mechanisms should be clarified.

Animals↗