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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 127 records · Page 7Linked to original sources
PubMed2001

Paradoxical role of Helicobacter pylori infection: protective effect against ethanol-induced gastric mucosal injury in Mongolian gerbils.

We investigated the effect of ethanol (a representative necrotizing agent) on gastritis induced by Helicobacter pylori infection in Mongolian gerbils. Seventy-eight gerbils were used. Four and 12 weeks after H. pylori inoculation, 30% ethanol was administered into the stomach. The stomachs were removed after 30 min, the intramucosal prostaglandin (PG) E2 concentration was measured, and histopathology was recorded. H. pylori infection caused chronic active gastritis, gastric erosion, hypersecretion of mucin from gland mucus cells, and a rise in the activity of intramucosal PGE2. After ethanol administration, gastric erosion was significantly less in animals infected with H. pylori than in uninfected animals. In conclusion, in the early stage of H. pylori infection, accentuation of intramucosal PGE2 and hypersecretion of mucin from gland mucus cells have a protective effect against gastric mucosal injury induced by necrotizing agents.

Animals↗
PubMed2001

Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotypes.

BACKGROUND: S-mephenytoin 4'-hydroxylase (CYP2C19) catalyses the metabolism of rabeprazole to some extent. Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole, rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19-related genetic polymorphism. AIM: To determine whether the pharmacodynamic effects of rabeprazole on intragastric pH and serum gastrin levels, and its pharmacokinetics depend on the CYP2C19 genotype status. METHODS: Eighteen healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. They consisted of six each of homozygous extensive metabolisers (homo EMs), heterozygous extensive metabolisers (hetero EMs), and poor metabolisers (PMs). Helicobacter pylori status was determined by serology. After a single oral dose of 10 mg or 20 mg rabeprazole or water only (baseline data), intragastric pH values were monitored for 24 h. Plasma levels of rabeprazole and serum gastrin were also measured for 24 h post-dose. RESULTS: Five homo EM, six hetero EM and four PM subjects were H. pylori-negative. After rabeprazole administration, significant differences in intragastric mean pH values, serum gastrin AUC(0-24) and plasma levels of rabeprazole were observed among the three different genotype groups. CONCLUSION: The pharmacodynamic effects of rabeprazole and its pharmacokinetics depend on the CYP2C19 genotype status.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Non-optically probing near-field microscopy with illumination of total internal reflection.

We have developed a non-optically probing near-field microscope with illumination of total internal reflection. Because the illumination light does not pass through the specimens, it is possible to observe thick specimens or highly absorptive materials. It reduces the background noise because the decay length of the evanescent wave is a few hundred nanometres. We found that although in the total internal reflection illumination system the light passed through the photosensitive film and illuminated the specimen, it did not affect the photosensitive film severely and did not limit the resolution. The imaging properties of reflection illumination and transmission illumination are analysed using a finite-differential time domain method.

Journal Article↗
PubMed2001

Mini-plasmin found in the epithelial cells of bronchioles triggers infection by broad-spectrum influenza A viruses and Sendai virus.

Extracellular cleavage of virus envelope fusion glycoproteins by host cellular proteases is a prerequisite for the infectivity of mammalian and nonpathogenic avian influenza viruses, and Sendai virus. Here we report a protease present in the airway that, like tryptase Clara, can process influenza A virus haemagglutinin and Sendai virus envelope fusion glycoprotein. This protease was extracted from the membrane fraction of rat lungs, purified and then identified as a mini-plasmin. Mini-plasmin was distributed predominantly in the epithelial cells of the upward divisions of bronchioles and potentiated the replication of broad-spectrum influenza A viruses and Sendai virus, even that of the plasmin-insensitive influenza A virus strain. In comparison with plasmin, its increased hydrophobicity, leading to its higher local concentrations on membranes, and decreased molecular mass may enable mini-plasmin to gain ready access to the cleavage sites of various haemagglutinins and fusion glycoproteins after expression of these viral proteins on the cell surface. These findings suggest that mini-plasmin in the airway may play a pivotal role in the spread of viruses and their pathogenicity.

Amino Acid Sequence↗
PubMed2001

KRH-594, a new angiotensin AT1 receptor antagonist, prevents end-organ damage in stroke-prone spontaneously hypertensive/Izm rats.

1. In the present study, we examined whether KRH-594, a new angiotensin AT1 receptor antagonist, would stop the progression of renal failure and end-organ damage and improve the survival rate in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2. Oral administration of KRH-594 (3 and 10 mg/kg per day) for 11 weeks significantly reduced systolic blood pressure, urinary total protein, blood urea nitrogen, serum creatinine and urinary N-acetyl glucosaminidase and increased creatinine clearance in SHRSP/Izm. 3. In a histological study, KRH-594 (3 and 10 mg/kg per day) significantly improved the glomerulosclerosis, basophilic change and hyalin cast of tubules, proliferation of afferent arterioles and interlobular artery wall scores of the kidney and the cardiac fibrosis scores of the heart in SHRSP/Izm. KRH-594 (3 and 10 mg/kg per day) also significantly inhibited cardiac hypertrophy. 4. KRH-594 (3 and 10 mg/kg per day) prevented death in SHRSP/Izm during the examination period. 5. These results suggest that KRH-594 improves hypertensive complications, such as renal failure, cardiac hypertrophy and thickening of the artery wall, and prevents death in salt-loaded SHRSP/Izm.

Angiotensin Receptor Antagonists↗
PubMed2001

Epithelial inclusion cyst (epidermoid cyst) formation with epithelioid cell granuloma in an intrapancreatic accessory spleen.

The histologic characteristics of a case of epidermoid cyst formation with an epithelioid cell granuloma that developed in intrapancreatic accessory spleen were investigated, with the aim of clarifying its origin as well as etiologic factors. The patient, a 48-year-old male, was found to have a cystic lesion in the tail of the pancreas and renal cell carcinoma (clear cell carcinoma) during a medical check up. The pancreatic mass appeared to be a so-called "mucinous tumor" on imaging, and combined resection of the body and tail of the pancreas and the spleen was performed together with a left nephrectomy. The lesion in the tail of the pancreas was then demonstrated to have accessory splenic tissue with cyst formation in its central region. The cystic wall was covered with stratified squamous epithelium and ductal epithelium with squamous metaplasia, and pancreatic islet cells were evident at various sites within the accessory spleen. Formation of epithelioid cell granuloma tissue was observed around the cysts. The epithelium of the cyst was positive for CA19-9 and negative for antibodies against mesothelial cells, whereas the pancreatic island cells were positive for insulin. These results suggested that cystic epithelium in the accessory spleen could be derived from pancreatic duct epithelium. Frequent recurrence of chronic inflammation and epitheloid cell granuloma formation may have resulted from an aberration of the ectopic remaining pancreatic tissue in the spleen.

Choristoma↗
PubMed2001

Endometrioid adenocarcinoma arising from adenomyosis: report and immunohistochemical analysis of an unusual case.

A case of endometrioid adenocarcinoma arising from adenomyosis is reported. The patient was a 53-year-old woman who complained of vulvar itching. Smear cytology of the endometrium revealed adenocarcinoma. Magnetic resonance imaging of the pelvis revealed a lesion with a slightly high intensity in the uterine fundus on a T2-weighted image. Semiradical total hysterectomy and bilateral adnexectomy were performed, followed by chemotherapy. Histologically, the lesion in the uterine fundus was composed mostly of adenocarcinoma with stromal invasion. There were many adenomyotic foci in and around the carcinoma, including some showing transition to adenocarcinoma. There was no malignant finding in the normally situated endometrium. The carcinoma invaded in the myometrium, involving the uterine serosa, but no dissemination to the peritoneal cavity was found. The carcinoma was, therefore, considered to be endometrioid adenocarcinoma arising from adenomyosis. Immunohistochemistry showed expression of p53 oncoprotein and Ki-67 antigen in the carcinoma cells. The value of immunohistochemistry in predicting prognosis is discussed.

Adenocarcinoma↗
PubMed2001

Prognostic significance of lymph node involvement in middle and distal bile duct cancer.

BACKGROUND: Although lymph node involvement is considered an important prognostic factor, a detailed analysis has not been conducted in middle (Bm) and distal (Bi) bile duct cancer. METHODS: The histopathology of resections taken from 59 patients with Bm and Bi disease (Bm, 33 patients; Bi, 26 patients) was examined. The prevalence of lymph node involvement and its relationship to recurrence and prognosis were investigated. Survival rates were investigated according to the number of metastatic lymph nodes found, the TNM nodal stages, and the nodal stage classifications of The General Rules of the Japanese Society of Biliary Surgery. RESULTS: The frequency of nodal involvement in Bm and Bi was 45.5% and 30.8%, respectively. A significant correlation existed between a patient's prognosis and his TNM nodal stage, Japanese Society of Biliary Surgery nodal stage, and the number of metastatic lymph nodes found (P <.0001, respectively). Among 8 sites of postoperative recurrence, metastasis occurred most frequently in the liver (16/23). Patients with nodal involvement had a significantly higher rate of liver metastasis (10/23) than those without it (6/36) (P =.024). CONCLUSIONS: The number of metastatic lymph nodes found in patients with Bm or Bi cancer, and the nodal stage of their nodes, are significant prognostic indicators. Patients with nodal involvement are at high risk for liver metastasis in Bm and Bi disease.

Adult↗
PubMed2001

Size distribution and meiotic competence of oocytes obtained from bitch ovaries at various stages of the oestrous cycle.

The present study was conducted to examine the effects of the stage of the oestrous cycle on the meiotic competence of canine oocytes and also to investigate the relationship between the stage of the oestrous cycle and the relative size distribution of oocytes obtained from bitches at three stages of the cycle (anoestrus, follicular phase and dioestrus). Only healthy-looking cumulus-oocyte complexes were used for in vitro maturation and these were divided into three groups based on diameter (< 110, 110 to < 120 and > or = 120 microm). The mean diameter of oocytes from ovaries at anoestrus, the follicular phase and dioestrus was 103.6, 119.2 and 107.7 microm, respectively. The percentage of large oocytes (> or = 120 microm) collected at the follicular phase was higher (P<0.01) than that collected at dioestrus and the percentage of oocytes > or = 120 microm collected from ovaries at dioestrus was higher (P<0.01) than that collected at anoestrus. After culture for 72 h, significantly more oocytes reached metaphase II (MII) in the follicular phase than in the other stages (P<0.01), and more oocytes reached MII in dioestrus than in anoestrus (P<0.05). In the > or = 120 microm group, the frequency of oocytes that resumed meiosis in the follicular phase was higher (P<0.05) than in the other stages. However, in the smaller diameter (< 120 microm) groups, there were no significant differences between ovaries at different stages of the oestrous cycle with respect to the proportion of oocytes reaching each stage of meiosis. Thus, the oestrous cycle stage influences maturation frequency. Moreover, oocytes demonstrated a size-related ability to undergo meiotic maturation, irrespective of the stage of the oestrous cycle. These results suggest that the effects of the stage of the oestrous cycle may result from differences in the distribution of large oocytes.

Anestrus↗
PubMed2001

Scrotal reconstruction with a thinned flap based on both inferior epigastric arteries. Case report.

A 62-year-old man presented with an extensive defect of the scrotum caused by Fournier's gangrene. We reconstructed the scrotum using a thinned flap based on both inferior epigastric arteries one month after the first debridement. This method has the advantage of achieving adequate mobility of the reconstructed scrotum. The results were satisfactory both functionally and cosmetically, although we had to repair a hernia at the donor site a year later.

Debridement↗
PubMed2001

Geranylgeranylacetone promotes induction and secretion of thioredoxin in gastric mucosal cells and peripheral blood lymphocytes.

Thioredoxin (TRX) is a redox-active protein which is induced by oxidative stresses and shows a variety of biological activities including cytoprotection against oxidative stress. We recently reported that geranylgeranylacetone (GGA), an anti-ulcer drug, induces TRX in rat hepatocytes. In this study, we demonstrate that GGA promotes induction and secretion of TRX in rat gastric mucosal cells and human peripheral blood lymphocytes (PBLs). Western blotting and a sensitive sandwich ELISA showed that TRX was induced by GGA in the cell lysates and culture supernatants of rat gastric mucosal RGM-1 cells and human PBLs. LDH releasing assay showed that GGA protected rat gastric mucosal RGM-1 cells from ethanol-induced cytotoxicity. Moreover, exogenous recombinant wild type TRX decreased 51Cr release from primary cultured rat gastric mucosal cells incubated with ethanol or hydrogen peroxide in a dose-dependent manner, whereas recombinant mutant TRX (C32S/C35S), in which the two cysteines were replaced with serines in its active site, did not. These results indicate that GGA promotes the induction and secretion of TRX in a variety of types of cells and suggest that induced or secreted TRX may play an important role in the cytoprotective action of GGA on gastric mucosal cells.

Animals↗
PubMed2001

Expansion of megakaryocyte progenitors from cryopreserved leukocyte concentrates of human placental and umbilical cord blood in short-term liquid culture.

Long-term severe thrombocytopenia following human placental and umbilical cord blood (CB) transplantation is a significant clinical problem. We studied the ex vivo expansion of megakaryocytic progenitor cells (CFU-Meg) from cryopreserved/thawed leukocyte concentrates (LC) of CB prepared by the Tokyo Cord Blood Bank protocol. The LC cells were cultured in serum-free culture medium supplemented with a combination of early-acting cytokines including thrombopoietin (TPO), flt3-ligand (FL), and stem cell factor (SCF). Combination of TPO plus FL, TPO plus SCF, and all of these cytokines together resulted in 8.9-, 7.7-, and 8.4-fold increases in CFU-Meg, respectively, by Day 5 of culture. Our results showed that this simple expansion strategy has the potential for expanding CFU-Meg from cryopreserved/thawed LC cells from CB.

Cell Culture Techniques↗
PubMed2001

Enhancement of oxidative damage to cultured cells and Caenorhabditis elegans by mitochondrial electron transport inhibitors.

The mechanisms that lead to mitochondrial damage under oxidative stress conditions were examined in primary and cultured cells as well as in the nematode Caenorhabditis elegans (C. elegans) treated simultaneously with electron transport inhibitors and oxygen gas. Oxygen loading enhanced the damage of PC 12 cells by thenoyltrifluoroacetone (TTFA, a complex II inhibitor), but did not by rotenone (a complex I inhibitor), antimycin (a complex III inhibitor), and sodium azide (a complex IV inhibitor). In primary hepatocytes, the enhancement was observed with the addition of sodium azide and rotenone, but not by TTFA or antimycin. In the nematode, only rotenone and TTFA enhanced the sensitivity under hyperoxia. These results demonstrate that highly specific inhibitors of electron transport can induce oxygen hypersensitivity in cell levels such as PC 12 cells and primary hepatocytes, and animal level of C. elegans. In addition the cell damage is different dependent on cell type and organism.

Animals↗
PubMed2001

Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin.

We describe Japanese siblings with resistance to thyrotropin (TSH) who are compound heterozygotes for two novel mutations in the TSH receptor gene. The affected siblings had increased serum TSH, normal serum thyroid hormones, and normal positioned but slightly hypoplastic thyroid glands. The mutated paternal allele has the substitution of His (CAC) in place of Arg (CGC) at codon 450 (R450H) of the TSH receptor. The mutated maternal allele has the substitution of Ser (AGT) in place of Gly (GGT) at codon 498 (G498S) of the TSH receptor. COS-7 cells transfected with the R450H mutant exhibited a slightly decreased TSH binding and a slightly decreased cyclic adenosine monophosphate (cAMP) response to TSH, whereas cells transfected with the G498S mutant exhibited a markedly decreased TSH binding and a markedly decreased cAMP response to TSH. Flow immunocytofluorometry analysis demonstrated that the G498S mutant resulted in extremely low expression at the cell surface as compared with the wild type receptor and the R450H mutant, in spite of a normal intracellular synthesis. The present cases are the first Japanese patients with TSH resistance in whom mutations in the TSH receptor gene have been identified. These novel mutations may contribute to understanding of the struc-ture-function relationship of the TSH receptor.

Adult↗
PubMed2001

Inhibition of azoxymethane-induced colon carcinogenesis in male F344 rats by the citrus limonoids obacunone and limonin.

The modifying effects of dietary administration of the citrus limonoids obacunone and limonin on azoxymethane (AOM)-induced colon tumorigenesis were investigated in two experiments in male F344 rats. In a pilot study, we examined the modifying effects of obacunone and limonin on AOM-induced (20 mg/kg body wt, once a week for 2 weeks) formation of aberrant crypt foci (ACF). Dietary feeding of both compounds at dose levels of 200 and 500 p.p.m. during AOM exposure for 4 weeks ('initiation' feeding) or after AOM treatment for 4 weeks ('post-initiation' feeding) significantly inhibited ACF formation (55-65% reduction by 'initiation' feeding, P < 0.001; 28-42% reduction by 'post-initiation' feeding, P < 0.05-0.002). In a long-term study designed to confirm the protective effects of obacunone and limonin on ACF development, one group was treated with AOM alone and another four groups received the carcinogen treatment plus diets containing 500 p.p.m. test compounds for 3 weeks (initiation phase) or 29 weeks (post-initiation phase). Two groups were treated with obacunone or limonin alone (500 p.p.m. in diet) and one group was maintained on the basal diet. At the termination of the study, dietary exposure to obacunone or limonin during the initiation phase was found to have significantly reduced the incidence of colonic adenocarcinoma (72 versus 25 or 6%, P = 0.004 or 0.00003). Obacunone or limonin feeding during the post-initiation phase also reduced the frequency of colonic adenocarcinoma (72 versus 13%, P = 0.0002). Our results suggest that the citrus limonoids obacunone and limonin might be useful for the prevention of human colon cancers.

Animals↗
PubMed2001

Low aquaporin content and low osmotic water permeability of the plasma and vacuolar membranes of a CAM plant Graptopetalum paraguayense: comparison with radish.

Aquaporin facilitates the osmotic water transport across biomembranes and is involved in the transcellular and intracellular water flow in plants. We immunochemically quantified the aquaporin level in leaf plasma membranes (PM) and tonoplast of Graptopetalum paraguayense, a Crassulacean acid metabolism (CAM) plant. The aquaporin content in the Graptopetalum tonoplast was approximately 1% of that of radish. The content was calculated to be about 3 microg mg(-1) of tonoplast protein. The level of PM aquaporin in Graptopetalum was determined to be less than 20% of that of radish, in which an aquaporin was a major protein of the PM. The PM aquaporin was detected in the mesophyll tissue of Graptopetalum leaf by tissue print immunoblotting. The osmotic water permeability of PM and tonoplast vesicles prepared from both plants was determined with a stopped-flow spectrophotometer. The water permeability of PM was lower than that of the tonoplast in both plants. The Graptopetalum PM vesicles hardly showed water permeability, although the tonoplast showed a relatively high permeability. The water permeability changed depending on the assay temperature and was also partially inhibited by a sulfhydryl reagent. Furthermore, measurement of the rate of swelling and shrinking in different mannitol concentrations revealed that the protoplasts of Graptopetalum showed low water permeability. These results suggest that the low content of aquaporins in PM and tonoplast is one of the causes of the low water permeability of GRAPTOPETALUM: The relationship between the water-storage function of succulent leaves of CAM plants and the low aquaporin level is also discussed.

Amino Acid Sequence↗
PubMed2001

DNA damage induced by red food dyes orally administered to pregnant and male mice.

We determined the genotoxicity of synthetic red tar dyes currently used as food color additives in many countries, including JAPAN: For the preliminary assessment, we treated groups of 4 pregnant mice (gestational day 11) once orally at the limit dose (2000 mg/kg) of amaranth (food red No. 2), allura red (food red No. 40), or acid red (food red No. 106), and we sampled brain, lung, liver, kidney, glandular stomach, colon, urinary bladder, and embryo 3, 6, and 24 h after treatment. We used the comet (alkaline single cell gel electrophoresis) assay to measure DNA damage. The assay was positive in the colon 3 h after the administration of amaranth and allura red and weakly positive in the lung 6 h after the administration of amaranth. Acid red did not induce DNA damage in any sample at any sampling time. None of the dyes damaged DNA in other organs or the embryo. We then tested male mice with amaranth, allura red, and a related color additive, new coccine (food red No. 18). The 3 dyes induced DNA damage in the colon starting at 10 mg/kg. Twenty ml/kg of soaking liquid from commercial red ginger pickles, which contained 6.5 mg/10 ml of new coccine, induced DNA damage in colon, glandular stomach, and bladder. The potencies were compared to those of other rodent carcinogens. The rodent hepatocarcinogen p-dimethylaminoazobenzene induced colon DNA damage at 1 mg/kg, whereas it damaged liver DNA only at 500 mg/kg. Although 1 mg/kg of N-nitrosodimethylamine induced DNA damage in liver and bladder, it did not induce colon DNA damage. N-nitrosodiethylamine at 14 mg/kg did not induce DNA damage in any organs examined. Because the 3 azo additives we examined induced colon DNA damage at a very low dose, more extensive assessment of azo additives is warranted.

Amaranth Dye↗