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Biomedical subjects

Y Niwa

Publications and source records attributed to Y Niwa.

At least 163 records · Page 9Linked to original sources

Hepatocyte growth factor induces mitogenic reaction to the rabbit gastric epithelial cells in primary culture.

Hepatocyte Growth Factor (HGF) was originally identified as hepatotrophic factor for liver regeneration. More recently, HGF was revealed to stimulate proliferation of various epithelial cells. At present study, we have investigated the mitogenic effect of HGF on gastric epithelial cells in the primary culture system. HGF remarkably stimulated proliferation of these cells dose dependently and synergistically with EGF and insulin. Mitogenic action of HGF might be mediated not by intracellular Ca2+ but by tyrosine kinase pathway. Conditioned medium of cultured fibroblast-like cells showed proliferative effects on cultured gastric epithelial cells in a similar way as exogenous HGF. These results suggest that HGF might be involved in the repair process of gastric mucosa.

Animals↗

Electromagnetic wave emitting products and "Kikoh" potentiate human leukocyte functions.

Tourmaline (electric stone, a type of granite stone), common granite stone, ceramic disks, hot spring water and human palmar energy (called "Kikoh" in Japan and China), all which emit electromagnetic radiation in the far infrared region (wavelength 4-14 microns). These materials were thus examined for effects on human leukocyte activity and on lipid peroxidation of unsaturated fatty acids. It was revealed that these materials significantly increased intracellular calcium ion concentration, phagocytosis, and generation of reactive oxygen species in neutrophils, and the blastogenetic response of lymphocytes to mitogens. Chemotactic activity by neutrophils was also enhanced by exposure to tourmaline and the palm of "Kikohshi" i.e., a person who heals professionally by the laying on of hands. Despite the increase in reactive oxygen species generated by neutrophils, lipid peroxidation from unsaturated fatty acid was markedly inhibited by these four materials. The results suggest that materials emitting electromagnetic radiation in the far infrared range, which are widely used in Japan for cosmetic, therapeutic, and preservative purposes, appear capable of potentiating leukocyte functions without promoting oxidative injury.

Adolescent↗

Short report: effect of sucralfate on angiogenesis in granulation tissue of acetic acid-induced gastric ulcers in rats.

We investigated the effect of sucralfate on angiogenesis in granulation tissue of gastric ulcers induced by acetic acid in rats using the carmine dye method. Intragastric administration of sucralfate at a dose of 500 mg/kg twice daily for 9 days significantly accelerated ulcer healing and significantly increased the extent of angiogenesis in the ulcer base on the tenth day after ulcer induction. As we reported previously, intragastric administration of cimetidine at a dose of 100 mg/kg once daily for 9 days decreased the extent of angiogenesis on the tenth day. However, combination treatment using sucralfate and cimetidine accelerated ulcer healing significantly, without altering the extent of angiogenesis. It is concluded, therefore, that the treatment with sucralfate may be effective in peptic ulcer disease from the standpoint of angiogenesis in the ulcer base.

Animals↗

The effect of oxatomide on neutrophil oxygen radical generation.

The effect of oxatomide on reactive oxygen species (ROS) generated both by neutrophils and in a cell-free, xanthine-xanthine oxidase system was examined. The species investigated were superoxide radical anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). Oxatomide significantly decreased neutrophil-generated O2-, H2O2 and OH. in a dose-dependent manner. H2O2 and OH. generated in a cell-free system were also reduced in the presence of oxatomide. The present study indicates that oxatomide decreases ROS generation presumably by inhibiting the neutrophil oxygen metabolism, and has the ability to scavenge H2O2 and OH.

Cell-Free System↗

Percutaneous ethanol injection therapy for hepatocellular carcinoma: results in 146 patients.

OBJECTIVE: Sonographically guided percutaneous ethanol injection therapy has been used widely in the treatment of hepatocellular carcinoma. However, few reports have been published on the results of this treatment in large numbers of patients. Accordingly, we describe our experience with 146 patients who had this treatment. The study is an update of our previous reports on this subject. SUBJECTS AND METHODS: We used ethanol injection, with or without transcatheter arterial embolization, 1048 times in 146 patients who had 242 lesions of hepatocellular carcinoma. In 98 patients, ethanol injection was used to attempt a cure of the disease. In the remaining 48 patients, ethanol injection was used palliatively only to reduce the tumor burden. In most cases, 2-8 ml of absolute ethanol was injected in one treatment session. Patients were given the injections two or three times each week until ethanol was injected throughout the lesion. When tumors were greater than 2 cm in diameter, ethanol was injected into the edges of the lesion. RESULTS: Histopathologic examination after treatment in 21 cases showed that the lesion was completely necrotic in 15 cases, 90% necrotic in five cases, and 70% necrotic in the remaining case. Follow-up angiography performed in 69 cases showed no contrast stains in the treated tumors in 60 cases. Elevated serum levels of alpha-fetoprotein decreased in 39 of 43 cases. The 1-, 2-, 3-, 4-, and 5-year survival rates of all 146 patients were 79%, 64%, 46%, 38%, and 38%, respectively. Among 98 patients in whom ethanol injection was used as a potentially curative therapy, these rates were 85%, 70%, 62%, 52%, and 52%, respectively. After ethanol injection, the cancer recurred frequently; the 1-, 2-, 3-, 4-, and 5-year recurrence rates in the potentially curative group were 26%, 38%, 51%, 60%, and 60%, respectively. However, 84% of recurrences were new lesions in different portions of the liver; recurrence of lesions treated by ethanol injection was rare. Major complications of the treatment were peritoneal bleeding in two cases and pleural effusion in one case. CONCLUSION: Histopathologic examination, angiography, and serum levels of alpha-fetoprotein showed that percutaneous ethanol injection is a valuable treatment of hepatocellular carcinoma. The therapy increased the long-term survival of patients who have this disease.

Carcinoma, Hepatocellular↗

Production of chemotactic factor, interleukin-8, from hepatocytes exposed to ethanol.

In a previous paper, we demonstrated proteinous chemotactic factors released from hepatocytes exposed to ethanol. In this study, we further characterized the chemotactic factors released from ethanol-treated hepatocytes. After fractionating the conditioned medium with gel chromatography, we demonstrated chemotactic activity at molecular weights of around 20 and 40 kD. When the conditioned medium was mixed with antiserum against interleukin-8, chemotactic activity was almost completely abolished. In addition, antiserum against interleukin-8 completely reduced chemotactic activity of the 20-kD chemotactic factor but did not influence the chemotactic activity of the 40-kD chemotactic factor. After gel electrophoresis of the conditioned medium, the protein reacted with antibody against interleukin-8 was demonstrated at a molecular weight of 20 kD but was not found at a molecular weight of 40 kD. These results suggest that a major part of the proteinous chemotactic factors released from hepatocytes exposed to ethanol could be a dimer form of interleukin-8, one of the proinflammatory cytokines, possibly contributing to the pathogenesis of alcoholic hepatitis.

Animals↗

Age-dependent basal level and induction capacity of copper-zinc and manganese superoxide dismutase and other scavenging enzyme activities in leukocytes from young and elderly adults.

Several enzymes, including superoxide dismutase (SOD), catalase, glutathione peroxidase, and D-glucose-6-phosphate dehydrogenase are capable of scavenging reactive oxygen species in in vivo. We assessed both basal levels and the capacity of these enzyme activities to be induced in human leukocytes in response to a variety of agents. Basal activity of copper-zinc SOD, and manganese SOD showed little variation with age. In contrast, the basal activity of the three H2O2 scavenging enzymes, catalase, glutathione peroxidase, and D-glucose-6-phosphate dehydrogenase, was significantly higher in younger adults than in elderly individuals. Both manganese SOD and copper, zinc SOD activities were significantly induced by paraquat, interleukin-1, tumor necrosis factor, adriamycin, and bleomycin in lymphocytes and neutrophils from asymptomatic non-aged adults, whereas neither activity was induced in aged individuals. In contrast, glutathione peroxidase activity was significantly induced in both groups of subjects, whereas catalase and D-glucose-6-phosphate dehydrogenase were only slightly induced in either. Enzyme induction with paraquat, adriamycin, or bleomycin was inhibitable by neutralizing antibody to interleukin-1 and tumor necrosis factor, suggesting that the inductions observed with these three drugs are due to the distal mediators, interleukin-1 or tumor necrosis factor released from the cells. Finally, as observed in the regulation of genes in eukaryotes (Storz et al: Bacterial defenses against oxidative stress. Trends Genetics 1990, 6:363-368, ref. 1) O2- and H2O2 seem to differ in the rate of change with age in both basal levels and inducibility under oxygen stress.

Adolescent↗

Endoscopic ultrasonography for assessing the horizontal extent of invasive gastric carcinoma.

Accurately determining the surgical resection line is essential for improving the prognosis of patients with gastric carcinoma. Endoscopic ultrasonography (EUS) was used to assess the horizontal extent of cancerous invasion below the mucosal layer. In 105 patients (110 lesions) with gastric carcinoma, ultrasonographic images of resected specimens were compared with histological findings. The horizontal extent of the hypoechoic region of in vitro ultrasound was compared with the horizontal extent of the cancerous invasion and fibrosis in histological sections. In cases showing echo patterns characteristic of peptic ulcerations within the tumor focus, the horizontal spread of the echo-poor region correlated well with the spread of fibrosis, but not with the cancerous lesion. In other cases with no ulceration, the horizontal spread of the echo-poor region corresponded well with the cancerous lesions. To evaluate oral invasion of the cancerous lesion below the mucosa, 16 patients with gastric carcinoma who had clips placed during endoscopy were subsequently examined by EUS. The use of EUS combined with the clips allowed for a more accurate diagnosis of the invasion, not only in the mucosa, but also into the submucosa and beyond. This combined diagnostic method was safe and useful for determining a suitable surgical resection line.

Gastric Mucosa↗

Expression and secretion of wheat germ agglutinin by Saccharomyces cerevisiae.

Genes encoding pre-protein and prepro-protein of wheat germ agglutinin isolectin 2 (WGA2) were chemically synthesized and expressed in the yeast Saccharomyces cerevisiae under the control of the ENO1 promoter. Yeast harboring either a pre-WGA2 or a prepro-WGA2 gene expression plasmid secreted a mature form of WGA2 into the culture medium. The amount of WGA2 secreted by the strain KS58-2Ddel, which has a ssl1 mutation causing a supersecretion of human lysozyme [Suzuki, K., Ichikawa, K. & Jigami, Y. (1989) Mol. Gen. Genet. 219, 58-64], was 20-fold greater than that secreted by the wild-type strain KK4. The recombinant WGA2 from the cells containing the prepro-WGA2 gene expression plasmid was purified to homogeneity by a three-step ion-exchange chromatography scheme. As in wheat, the N-terminal signal peptide of recombinant WGA2 purified from yeast culture was processed to form an N-terminal 5-oxoprolyl (pyroglutamyl) residue. Likewise, we found that the C-terminal pro-region of recombinant WGA2 had also been processed in yeast. Using electrospray ionization mass spectrometry, we found the processed C-terminus to be heterogeneous in both recombinant WGA2 purified from yeast and in authentic WGA2. The major component of the recombinant WGA2 contained two additional amino acids at its C-terminus compared to that of authentic WGA2. In spite of this difference in the C-terminus, the recombinant WGA2 exhibited a sugar binding activity that was indistinguishable from that of authentic WGA2.

Amino Acid Sequence↗

Changes in lipid peroxide levels and activity of reactive oxygen scavenging enzymes in skin, serum and liver following UVB irradiation in mice.

The effect of acute UVB on the generation of reactive oxygen species (ROS) in the skin and the induction of ROS scavenging enzymes in situ was examined. Lipid peroxide levels and the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and D-glucose-6-phosphate dehydrogenase (G-6-P-D) were determined in the skin, serum, and liver of ICR mice subjected to 1400 mJ/cm2 of acute UVB irradiation. In irradiated skin, lipid peroxides were increased at 3 and 24 hr after irradiation, whereas the four ROS scavenging enzymes were generally decreased during the first 48 hr after irradiation. In the serum, lipid peroxides showed an increase at 3 hr, but enzyme activities remained negligible. In the liver, lipid peroxides showed similar behaviour to that in skin. GSH-Px activity in the liver was decreased during the first 24 hr, whereas G-6-P-D showed substantial fluctuation and SOD and catalase activities showed no change. These data are consistent with a model in which lipid peroxides generated in the UVB-irradiated lesions are transported to the liver and there metabolized by the scavenging enzymes induced in situ.

Animals↗

[The relationship between evaluation of school stressors and stress responses in junior high school students].

The purpose of this study is to develop a school stressor scale from the events experienced frequently by junior high school students in their daily school life, and to examine the relationship between school stressors and stress responses. In study I, factor analysis of data by 552 students revealed four main factors "teacher", "friend", "club activity", and "study", which were extracted from initial set of 72 items. In study II, factor analysis of 50 items, of which 39 items were extracted in study I, and 11 new items of free-description type, of data by 622 students, revealed that main stressors in junior high school were following six, "teacher", "friend", "club activity", "study", "rule", and "official activity". Furthermore, multiple regression analyses revealed that "friend" strikingly correlated with "depressive-anxious emotion" and "study" did with "cognition-thought of helplessness".

Adolescent↗

Effect of doxycycline on the generation of reactive oxygen species: a possible mechanism of action of acne therapy with doxycycline.

On the basis of a recent report that minocycline is effective in the treatment of acne inflammation by acting directly as an antioxidant on infiltrating neutrophils, we investigated whether doxycycline might also be capable of reducing the generation of reactive oxygen species, using human neutrophils and a cell-free, xanthine-xanthine oxidase system. The species investigated are superoxide radical anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). Doxycycline significantly reduced the levels of O2-, H2O2 and OH. generated by both systems. Our results seem to suggest that the clinical effectiveness of doxycycline in the treatment of acne inflammation is due partly to its antioxidant effect on neutrophils.

Doxycycline↗

[Bezafibrate myopathy in two patients with chronic renal failure].

Case 1, a 60-year-old man and case 2, a 70-year-old man had several year history of chronic renal failure with hypertension and hyperlipidemia due to diabetes mellitus. Treatment of hyperlipidemia was started by oral bezafibrate intake 1,200 mg per day in case 1 and 400 mg per day in case 2 respectively. Three to fourteen days later, both patients noticed symmetrical muscle pain and weakness. Then the symptoms worsened and they were hospitalized. At the time of admission, both patients revealed weakness in the proximal muscles of their upper and lower limbs and the serum creatine kinase and myoglobin levels were remarkably elevated. Myoglobinuria was also noted. Routine light microscopic examination of biopsied quadriceps femoris muscles of two patients showed scattered necrotic muscle fibers, some of which were under phagocytosis. The symptoms of the patients were immediately resolved after the drug was discontinued. Serum concentration of bezafibrate was remarkably elevated during treatment. Thus the diagnosis was established as having bezafibrate induced myopathy and, as far as we know, this is the first report of bezafibrate induced myopathy in Japan. On the basis of the above description, bezafibrate may induce muscle damage if dose is excess over the renal capacity. Extreme caution is warranted when the patient is placed on bezafibrate and has renal dysfunction. Strict dose adjustment is necessary in taking account of renal function to avoid muscle damage including rhabdomyolysis.

Aged↗

[Relapse of peptic ulcer after quick healing induced by proton pump inhibitors].

Peptic ulcers treated with a proton pump inhibitor heal more quickly than those treated with a histamine H2 receptor antagonist. Although satisfactory healing without relapse is desirable in the medical treatment of peptic ulcers, the relapse rate after treatment with proton pump inhibitors has not been sufficiently studied. Up to now, several reports have suggested that peptic ulcers treated with omeprazole recur less frequently than those treated with H2 antagonists. Our experimental studies on angiogenesis in granulation tissue of acetic acid-induced gastric ulcers, gastric mucosal collagen synthesis etc., show that H2 antagonists have an inhibitory effect on wound healing, but that proton pump inhibitors do not. It is suggested, therefore, that proton pump inhibitors may at least have no undesirable effect on the natural history of peptic ulcer.

Adenosine Triphosphatases↗

The domestication of Crocidura dsinezumi as a new laboratory animal.

The dsinezumi shrew (Crocidura dsinezumi), a small insectivore, has been bred for the first time as a laboratory animal. The original animals were captured using Sherman's live traps and transferred into wooden cages. After several generations they were housed in plastic cages. Their diet consisted of trout pellets, cat food, and water provided ad libitum. Monogamous pairs were housed together for 2-3 weeks for mating, and the male was separated from the female during delivery and nursing. In captivity, the reproductive activity was observed throughout the year and the gestation period was estimated at 28-30 days with a litter size of between 1 and 4 pups. Pups grew very rapidly, and reached adult body size (mean: male, 9.7 g; female, 8.3 g) and sexual maturation at 6-8 weeks of age. The reproductive life was estimated at one and a half years, while the longevity was approximately 2 years.

Animal Husbandry↗

Prevalence of gallbladder polyps among apparently healthy Japanese: ultrasonographic study.

The prevalence of gallbladder polyps was investigated in apparently healthy Japanese who underwent abdominal ultrasonography as part of their health screening examination. The polyps found were differentiated from gallstones, adenomas, or carcinomas as much as possible, and were considered to be cholesterol polyps. The prevalence of such gallbladder polyps was higher among males in every decade of age evaluated. The subjects with gallbladder polyps were more obese than the control group without gallbladder polyps, on abdominal ultrasonograms. The prevalence of gallbladder polyps rose in accordance with a rise in obesity index. At each range of obesity index, the prevalence of gallbladder polyps was higher among males. The prevalence of gallbladder polyps was highest among the middle-aged (40- and 50-yr-old) males, similar to the curve of the obesity index. In females, the obesity index increased with age, with no accompanying rise in the prevalence of gallbladder polyps. These data suggest that obesity contributes to the formation of cholesterol polyps of the gallbladder.

Adolescent↗

Anemia and mast cell depletion in mutant rats that are homozygous at "white spotting (Ws)" locus.

Mice possessing two mutant alleles at the W or Sl locus are anemic and deficient in mast cells. These mouse mutants have black eyes and white hair. Because homozygous mutant rats at the newly found white spotting (Ws) locus were also black-eyed whites, the numbers of erythrocytes and mast cells were examined. Suckling Ws/Ws rats showed a severe macrocytic anemia and were deficient in mast cells. When bone marrow cells of normal (+/+) control or Ws/Ws rats were injected into C3H/He mice that had received cyclophosphamide injection and whole-body irradiation, remarkable erythropoiesis occurred in the spleen of +/+ marrow recipients but not in the spleen of Ws/Ws marrow recipients. When skin pieces of Ws/Ws embryos were grafted under the kidney capsule of nude athymic rats, mast cells did develop in the grafted skin tissues. Therefore, the anemia and mast cell deficiency of Ws/Ws rats were attributed to a defect of precursors of erythrocytes and mast cells. Because the magnitude of the anemia decreased and that of the mast cell deficiency increased in adult Ws/Ws rats, this mutant is potentially useful for investigations about differentiation and function of mast cells.

Anemia↗

Characterization of Ws mutant allele of rats: a 12-base deletion in tyrosine kinase domain of c-kit gene.

Homozygous mutant rats at the newly found white spotting (Ws) locus were anemic and deficient in mast cells and melanocytes. Because the phenotype of Ws/Ws rats resembled the phenotype of mice possessing a double-gene dose of mutant alleles at the W locus and because the c-kit gene was mapped at the W locus of mice, we characterized the c-kit gene of Ws/Ws rats. The authentic sequence of the rat c-kit cDNA was determined by using a cDNA library prepared from the hippocampus of Sprague-Dawley rats. The c-kit cDNA of Ws/Ws and normal (+/+) control rats was obtained by reverse transcriptase modification of the polymerase chain reaction. When compared with the authentic sequence, a deletion of 12 bases was found in the c-kit cDNA of Ws/Ws rats. This change was shown to be a result of the deletion of the genomic DNA. Four amino acids encoded by the deleted 12 bases (ie, Val-Lys-Gly-Asn) were located at two amino acids downstream from the tyrosine autophosphorylation site in the c-kit kinase and were conserved not only in mouse and human c-kit kinases but also in mouse and human c-fms kinases (ie, receptors of colony-stimulating factor-1). Taken together, the Ws/Ws rat is the first characterized mutant of the c-kit gene in an animal species other than the mouse.

Alleles↗