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Biomedical subjects

K Morise

Publications and source records attributed to K Morise.

At least 37 records · Page 2Linked to original sources

Successful treatment of primary sclerosing cholangitis with cyclosporine and corticosteroid.

A case of primary sclerosing cholangitis (PSC) successfully treated with cyclosporine is described. A 65-year-old man who presented with jaundice and anemia was diagnosed as having PSC, accompanied by pancreatic duct abnormalities. Cholangiography and pancreatography showed marked improvements following combined therapy with cyclosporine and methylprednisolone. Cyclosporine seems to be a promising drug for the treatment of patients with PSC. This report reasons that the same disease process affects both the pancreatic ducts and the bile ducts, and that stagnation of pancreatic juice may have a role to play in the pancreatic duct abnormalities.

Aged↗

Combination chemotherapy with Tegafur. Uracil (UFT), etoposide, adriamycin and cisplatinum (UFT-EAP) for advanced gastric cancer.

Thirty-four patients with advanced gastric cancer were treated with combination chemotherapy employing Tegafur-Uracil (UFT), etoposide, Adriamycin, and Cisplatinum (CDDP) (UFT-EAP therapy). An objective partial response was obtained in 16 patients (47%) and the median duration of remission was 12.2 months. The 50% survival time for all 34 patients was 10 months. Patients with moderately or well differentiated adenocarcinoma responded well (13/19, 68%), while those with undifferentiated adenocarcinoma showed a poor response (3/15, 20%). Six responding patients were noted to have no evidence of viable cancer at the primary site by endoscopic biopsy, and underwent gastrectomies. The resected specimens showed complete disappearances of the primary tumors in four patients. The median survival time for the patients receiving gastrectomies was 24 months. The regimen was very well tolerated, apart from moderate bone marrow suppression. Our results suggest that patients with advanced gastric cancer can be effectively treated with UFT-EAP chemotherapy.

Adenocarcinoma↗

[Immunohistochemical study of Helicobacter pylori and mononuclear cells in the gastric mucosa of patients with gastritis or peptic ulcer].

The distribution and localization of Helicobacter pylori (HP) and mononuclear cells (MNC) in the gastric mucosa were investigated immunohistochemically in 120 patients with gastritis or peptic ulcer. HP was detected in the gastric mucosa of 58% of 40 gastritis patients, 82% of 56 gastric ulcer (GU) patients, and 88% of 24 duodenal ulcer (DU) patients. In the HP-positive mucosa, cells positive for IgG or IgA were increased significantly when compared to the HP-negative mucosa. Neutrophils and eosinophils were also increased under the HP-infected surface and therefore these cells were likely involved in the mucosal damage. Enhancement of the expression of HLA-DR antigen was observed in the gastric epithelium with HP infection and it was associated with a significant increase of lymphoid follicles and B cells in the mucosa. In comparison with the HP-infected mucosa of gastritis patients, the number of MNC were increased significantly in the mucosa of both DU and GU patients. The number of HP in the gastric mucosa of DU patients was significantly higher than those of both gastritis and GU patients. In addition, the grade of the infiltration of MNC and IgA positive cells were always greater in DU than in gastritis, regardless of the number of HP. These findings suggested that activation of the local immunity in the gastric mucosa of gastritis and peptic ulcer patients by HP infection may participate in the pathogenesis of gastroduodenal mucosa damage.

Adult↗

A phase II study of combination therapy with 5'-deoxy-5-fluorouridine and cisplatin in the treatment of advanced gastric cancer with primary foci.

BACKGROUND: 5'-Deoxy-5-fluorouridine (5'-DFUR, doxifluridine) is a recently developed prodrug of oral 5-fluorouracil (5-FU), which is used clinically in Japan for the treatment of gastric, colorectal, and breast cancer. 5-FU has been reported to act synergistically with cisplatin (CDDP) in experimental and clinical studies. The authors conducted a multicenter Phase II study of combination therapy with 5'-DFUR and CDDP to evaluate the therapeutic usefulness of this regimen in the treatment of unresectable and advanced gastric cancers with primary foci. None of the patients had previously undergone chemotherapy. Their ages ranged from 27 to 75 years and performance status was grade 0 to 3. METHODS: 5'-DFUR (1400 mg/m2/d) was administered orally on days 1 through 4 and 15 through 18, and CDDP (80 mg/m2/d) was injected intravenously on day 5. This treatment cycle was repeated every 4 weeks. An independent panel of specialists evaluated the clinical response. RESULTS: Fifty-one patients were studied. Clinical evaluation of response was possible in 43 patients who met the protocol requirements. The overall response rate was 50.0% (14 of 28, 95% confidence limits, 30.7%-69.4%) for patients with measurable lesions. The median duration of response was 5.2 months (156 days). The overall median survival time was 8.9 months (268 days) for evaluated patients. Therapeutic toxicity of World Health Organization (WHO) grade > or = 3 was manifested as anorexia and nausea or vomiting in 20.9% and 18.6% of the patients, respectively. However myelotoxicity and nephrotoxicity of WHO grades 3 and 4 occurred in less than 10% of the patient group. No drug-related mortality occurred. CONCLUSIONS: Combined therapy with 5'-DFUR and CDDP is a safe and effective treatment regimen for advanced gastric cancers with primary foci which stresses the patient's quality of life, especially when used in an outpatient setting.

Adenocarcinoma↗

The role of thyrotropin-releasing hormone (TRH) in the pathogenesis of water-immersion stress in rats--inhibition of TRH release from the stomach by atropine, ranitidine or omeprazole.

The role of thyrotropin-releasing hormone (TRH) in the development of gastric erosions and ulcers induced by water-immersion stress was studied. Intraperitoneally administered bethanechol induced a decrease in the gastric wall immunoreactive TRH (ir-TRH) concentrations and an increase in gastric juice ir-TRH concentrations in a dose-related manner, while atropine induced an increase in gastric wall ir-TRH concentrations and a decrease in gastric juice ir-TRH concentrations under non-stress condition. Intraperitoneally administered omeprazole did not influence gastric wall ir-TRH concentrations but elevated gastric pH. Water-immersion stress induced a decrease in gastric wall ir-TRH concentrations and an increase in gastric juice ir-TRH concentrations with a decrease in gastric pH prior to ulcer formation. Pretreatment with atropine or ranitidine inhibited the development of stress ulcers, reduced changes in ir-TRH concentrations in the gastric wall and gastric juice, and induced an increase in gastric pH. Omeprazole inhibited stress ulcer formation and changes in gastric wall and gastric juice ir-TRH concentrations. These results suggest that TRH release from the stomach wall into gastric juice is of importance in the pathogenesis of stress ulcer and that its release is mediated by both muscarinergic and histaminergic (H2) systems. Furthermore, omeprazole has an inhibitory effect on TRH release under stress ulcer.

Animals↗

Immunoreactive-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa in patients with nonulcer dyspepsia and peptic ulcer disease.

Changes in immunoreactive (ir)-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa were examined in subjects with nonulcer dyspepsia (NUD) and peptic ulcer to clarify the relationship between these peptides and dyspeptic symptoms. Fifty-six patients with NUD were divided into two subject subgroups as follows: 22 patients with upper abdominal discomfort, nausea, and/or vomiting (motility disorder group) and 34 patients complaining of upper abdominal pain [ulcer-like disorder (UD) group]. These patients were compared with either an age- and sex-matched group of asymptomatic outpatients without any organic disease (control group: n = 51), or to a group with peptic ulcer (PU group: n = 30). Ir-somatostatin concentrations of the gastric mucosa were significantly higher in UD group than in PU, motility disorder, or control group, and ir-substance P concentrations in the UD group were higher than in the PU group. No difference in ir-calcitonin gene-related peptide concentrations was observed among the four groups. These results indicate that there may be two distinct subgroups in NUD, and that NUD is not just a stage within the spectrum of peptic ulcer disease from the viewpoint of several gastrointestinal-hormone concentrations of the human gastric mucosa.

Biopsy↗

Helicobacter pylori infection induces a decrease in immunoreactive-somatostatin concentrations of human stomach.

Immunoreactive-somatostatin (ir-somatostatin) concentrations of the gastric mucosa and gastric juice with Helicobacter pylori infection were measured in the human stomach. One hundred seventy-one patients (106 males, 65 females; mean age, 52.0; range, 19-84 years) were registered. Gastric juice and mucosa were obtained with the usual endoscopy procedure. Somatostatin concentration was measured by radioimmunoassay. The ir-somatostatin concentrations in the H. pylori-negative group were significantly higher than in the positive group gastric mucosa, whereas its levels in gastric juice tended to decrease with H. pylori infection. There was an inverse correlation between luminal ammonia levels and ir-somatostatin concentrations of the gastric mucosa. On the other hand, ir-somatostatin concentrations of the gastric mucosa significantly decreased with chronic and active inflammatory change. This decrease was not correlated with the grade of active inflammation, which was in close relation to H. pylori infection, but with the grade of chronic inflammation. These results indicate that H. pylori may reduce ir-somatostatin concentrations of the human stomach and that its effect is partly mediated via luminal ammonia produced by H. pylori.

Adult↗

Effect of luminal administration of thyrotropin-releasing hormone or somatostatin on gastric pH and interaction of these peptides in rats.

The effect of intraluminal administration of thyrotropin-releasing hormone (TRH) on gastric pH and release of luminal somatostatin, and a possible interrelationship between TRH and somatostatin in the rat stomach were studied. TRH was administered into the stomach via an intragastric tube at various doses (50 pg/kg-10 micrograms/kg) and gastric pH was measured after 15 min. The intraluminal administration of TRH significantly decreased gastric pH at doses over 1.0 ng/kg. Time-course studies at a dose of 100 ng/kg TRH exhibited a significant decrease in gastric pH at 15, 30 and 60 min. Furthermore, TRH administration caused a significant increase in immunoreactive-somatostatin (ir-somatostatin) concentrations in the gastric wall and a significant decrease in ir-somatostatin concentrations in the gastric juice. On the other hand, intraluminal administration of somatostatin caused a significant increase in ir-TRH concentrations in the gastric wall and a significant decrease in ir-TRH concentrations in the gastric juice, and significantly raised gastric pH at 5 min. These findings suggest that luminal TRH may exert a regulatory effect on gastric acid secretion, and that TRH may have a possible interaction with somatostatin in the modulation of gastric acid secretion.

Animals↗

Effect of serotonin on the immunoreactive thyrotropin-releasing hormone concentrations of the rat stomach.

The effects of serotonin and its related compounds on immunoreactive thyrotropin-releasing hormone (ir-TRH) concentrations of the rat stomach wall and gastric juice were studied. Either serotonin, cyproheptadine or GR38032F was injected intraperitoneally, and the rats were decapitated at various times after the injection. ir-TRH concentrations of the stomach wall and gastric juice were measured by radioimmunoassay, and gastric serotonin concentrations were measured by HPLC. ir-TRH concentrations of the stomach wall decreased, and ir-TRH concentrations of gastric juice increased significantly after serotonin injection. On the other hand, both cyproheptadine and GR38032F did not affect ir-TRH concentrations of the stomach. The effects of serotonin on ir-TRH concentrations of the stomach were significantly blocked by the pretreatment of cyproheptadine and GR38032F. The reciprocal changes of gastric ir-TRH and serotonin concentrations were observed without changes in gastric juice pH. These findings suggest that serotonin stimulates ir-TRH release from the stomach wall into gastric juice, and the effects of serotonin on ir-TRH release may be partly mediated via 5-HT2- and 5-HT3-receptors.

Animals↗

[Role of gut hormones in irritable bowel syndrome].

In irritable bowel syndrome (IBS), motility disturbances occur from the upper gastrointestinal tract to the distal colon, where regulatory peptides have a wide-spread distribution. Studies on basal and postprandial plasma levels of different gut hormones show that VIP, CCK, and motilin may be closely related to the symptoms including abdominal pain, diarrhea and constipation. In addition, peptide YY and NPY have effects on absorption in the intestine, and some opioid peptides exert actions on colonic motility in IBS patients. Recent studies revealed that gall bladder in IBS has an abnormal sensitivity to CCK-8, indicating that IBS patients has an generalized abnormality of the smooth muscle of the digestive tract. Gut hormones, which act as hormones, neurotransmitters and neuromodulators depending on their releasing site, may therefore play an important role in IBS patients.

Animals↗

[Effect of a long-term oral ammonia administration on immunoreactive-somatostatin concentrations of rat stomach].

The effect of a long-term oral ammonia administration on immunoreactive-somatostatin concentrations was investigated in rat stomach. The gastric ir-somatostatin concentrations in the group treated with 0.01% ammonia (pH 9.6) for four weeks were significantly higher than those in both the group treated with 0.1% ammonia (pH 10.4), 0.1 mM-NaOH (pH 9.6), or distilled water (pH 7.0) for four weeks and the group treated with 0.01% ammonia for two weeks. On the contrary, ir-somatostatin levels in the gastric juice and serum tended to decrease with ammonia administration. Further, ammonia administration significantly induced the decrease in mucosal thickness in the pyloric gland area and parietal cell numbers in a dose- and time-dependent manner. From these findings, it was suggested that a long-term oral treatment with 0.01% ammonia, which was clinically estimated as the concentration of the gastric juice in patients with Helicobacter pylori infection, induced not only atrophic changes on gastric mucosa, but the inhibitory effect on somatostatin secretion in rat stomach.

Administration, Oral↗

Immunohistochemical study of T cell receptor gamma delta cells in chronic liver disease.

The distribution and phenotypic characterization of T cell receptor (TCR) gamma delta cells in human liver tissue was investigated immunohistochemically at light and electron microscopic levels. In chronic liver disease, there was a significant increase in the number of TCR gamma delta cells and in the percentage of TCR gamma delta cells to CD3+ cells in the portal areas and hepatic sinusoids. Hepatic TCR gamma delta cells were classified as small or large gamma delta cells. Large gamma delta cells were increased in chronic liver disease, whereas both small and large gamma delta cells were increased in the portal areas and hepatic sinusoids in liver cirrhosis. The increased TCR gamma delta cells were of the BB3+ (peripheral) type, indicating that TCR gamma delta cells in the liver were of the same lineage as those in the peripheral blood. In addition, the majority of the TCR gamma delta cells in the portal areas of liver cirrhosis patients were CD4- and CD8- (double negative). Immunoelectron microscopy showed that the large gamma delta cells were lymphoblastoid and contained multivesicles. The present study clearly demonstrated that there are two types of TCR gamma delta cells, and that these cells were significantly increased in the livers of patients with chronic liver disease. This suggests that they may be involved in regulation of the immune response and hepatocellular damage in chronic liver disease.

Adult↗

Phenotypic and functional analysis of lamina propria mononuclear cells from colonoscopic biopsy specimens in patients with ulcerative colitis.

Phenotypic and functional analysis was performed with lamina propria mononuclear cells (LPMCs) isolated from colonoscopic biopsies in 27 patients with ulcerative colitis (UC). The proportion of T lymphocytes displaying HLA-DR antigens, interleukin 2 (IL-2) receptor, and transferrin receptor was greater in active UC than in control diseases. When LPMCs were cultured with IL-2 or phytohemagglutinin for 72 h, there were no significant differences in the proportion of cells bearing these activation markers between active UC and controls. The proportion of CD56+ cells and lymphokine-activated killer (LAK) cell activity was lower in LPMCs from active UC than in control cells, and depletion of CD56+ cells from control lamina propria cells essentially eliminated LAK cell activity. Mucosal T lymphocytes may be activated in vivo during active inflammation in UC, and lower levels of intestinal LAK cell activity may be related to the decrease of CD56+ cells under these conditions.

Adolescent↗

[Immunohistochemical analysis of colonic mucosa with ulcerative colitis--activation of lymphocytes and expression of ICAM-1 by lamina propria dendritic cells and macrophages].

The colonic mucosa of 30 patients with ulcerative colitis was analyzed by an immunohistochemical technique. A quantitative evaluation for lymphocyte subsets show significantly increased numbers of CD3+, CD4+, CD8+, and CD28+ cells in ulcerative colitis cases of histological grades 3, 4 and 5 by Matts' classification comparing to normal control cases. CD4/CD8 ratio in each histological grade of ulcerative colitis was not significantly different from those in normal controls and disease controls (infectious colitis cases). However, CD28/CD3 ratio was increased significantly in ulcerative colitis cases of histological grades 3, 4 and 5 comparing to control cases. Most of the lymphocytes were positive for lymphocyte function-associated antigen-1 alpha (LFA-1 alpha). There were increased numbers of S100-beta + dendritic cells and CD68+ macrophages in the luminal area of the lamina propria. Moreover double stainings revealed that most of the S100-beta + dendritic cells and CD68+ macrophages were intercellular adhesion molecule-1 (ICAM-1, a ligand for LFA-1) positive. These findings suggested that the expression of ICAM1 on S100-beta + dendritic cells and CD68+ macrophages is important by the interaction with T cells and T cell antigen recognition.

CD4-CD8 Ratio↗

Effects of water-immersion-induced stress and intraperitoneal administration of brain-gut peptides upon immunoreactive thyrotropin-releasing hormone and prostaglandin E2 concentrations in the rat stomach.

The effects of water-immersion-induced stress and intraperitoneal (i.p.) administration of selected neuropeptides on the levels of thyrotropin-releasing hormone (TRH) and prostaglandin E2 (PGE2) were studied in the rat stomach. Water-immersion caused a significant decrease immunoreactive-TRH (ir-TRH) concentrations in the stomach, and a significant increase in ir-TRH concentrations in the gastric juice. The concentrations of PGE2 were significantly increased at 0.5-4 hrs, and significantly decreased at 6-8 hrs after water-immersion. In the experiment of i.p. administration of selected neuropeptides, the level of ir-TRH in the stomach was significantly decreased after VIP injection, whereas it was significantly increased after beta-endorphin injection. The concentration of PGE2 was significantly decreased in the stomach after i.p. administration of TRH and VIP. However, it did not change after beta-endorphin injection. These results indicate that some neuropeptides may participate in regulating the endogenous level of PGE2 and that these interrelations between neuropeptides and PGE2 may be important as ulcerogenic factors in stress ulcers induced by water-immersion in the rat.

Animals↗