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T Ohkusa

Publications and source records attributed to T Ohkusa.

At least 73 records · Page 4Linked to original sources

Influence of aortic impedance on the development of pressure-overload left ventricular hypertrophy in rats.

BACKGROUND: Aortic input impedance, which represents LV afterload, is considered to be a major determinant for the development of pressure-overload left ventricular (LV) hypertrophy. METHODS AND RESULTS: To test whether the sustained change in aortic input impedance might affect the mode of development of LV hypertrophy, coarctation of either the ascending aorta (G1, n = 13) or suprarenal abdominal aorta (G2, n = 12) was performed over 4 weeks in 6-weeks-old Wistar rats. Although peak LV pressure and total systemic resistance were increased similarly in G1 and G2, time to peak LV pressure was decreased by 24% (P < .01) in G1 compared with G2. The aortic input impedance spectra revealed that the early systolic loading in G1 was characterized by an increase in characteristic impedance, whereas the late systolic loading in G2 was by an augmented arterial wave reflection. G1 showed a smaller increase (P < .01) in either the ratio of LV weight (mg) to body weight (g) or LV wall thickness than G2 after aortic banding. Myocyte diameter was also smaller (P < .05) in G1 (14.3 +/- 0.7 mm) than in G2 (16.1 +/- 1.2 mm). The ex vivo passive pressure-volume relation had a rightward shift in G1 compared with G2, suggesting less concentric LV hypertrophy in G1. CONCLUSIONS: The sustained early systolic loading due to the increase in characteristic impedance was accompanied by less concentric, reduced hypertrophy, whereas the sustained late systolic loading due to the augmented arterial wave reflection was accompanied by concentric, adequate hypertrophy.

Aldosterone↗

Population changes in immunoglobulin-containing mononuclear cells in dextran sulfate sodium-induced coltitis.

To investigate the relation of immunoglobulin-containing cells in the colonic mucosa to mucosal inflammation, we immunohistochemically examined the localization of immunoglobulin-containing mononuclear cells in the lamina propria in dextran sulfate sodium induced colitis in mice. Mice were treated repeatedly with 3% dextran sulfate sodium (MW 54,000) solution or distilled water for a total of 170 days (chronic model), or for 85 days (subacute model) or for 10 days (acute model). IgG, IgA, and IgM-containing mononuclear cells were studied by enzyme immunostaining. The number of IgA- and IgG-containing cells gradually and significantly increased in the acute, subacute, and chronic models, in that order (P < 0.01 or 0.05). However, the numbers of IgM-containing cells in the three models were similar to that in the controls. These findings resembled those of human ulcerative colitis. In this dextran sulfate sodium-induced colitis, IgA-containing mononuclear cells may play an essential role in the mucosal immune system is the acute, subacute, and chronic phases. The finding that IgG-containing mononuclear cells increased substantially in the chronic phase suggests that IgG plays an important role in the mucosal inflammatory reaction during the chronic phase.

Acute Disease↗

Promotion of colorectal neoplasia in experimental murine ulcerative colitis.

BACKGROUND: The mechanisms underlying the frequent development of colorectal carcinomas in patients with ulcerative colitis are still unknown. AIMS: To evaluate whether mucosal necrosis and regeneration act as enhancing or promoting factors in colorectal tumorigenesis, development of multiple colorectal tumours was studied in a murine model of ulcerative colitis with azoxymethane pretreatment. METHODS: Periods of chronic ulcerative colitis in mice were induced by three repeated administrations of 3% dextran sulphate sodium subsequent to a single azoxymethane pretreatment, to give conditions similar to the clinically observed active and remission phases. RESULTS: In the chronic colitis group with carcinogen exposure, multiple mucosal tumours (10.5/mouse) developed in the colorectum. This occurred primarily on the left side of the large intestine or transverse colon, the sites of the most severe colitic injury. The observed lesions were high grade dysplasias and invasive adenocarcinomas. Increased cell proliferation was evidenced by high uptake of bromodeoxyuridine, and increased activities of thymidylate synthetase and thymidine kinase. No tumours were induced in the control groups with azoxymethane pretreatment or chronic colitis alone. CONCLUSIONS: Repeated mucosal erosion with necrosis and regeneration is critical for the development of colorectal tumours in this experimental colitis system.

Animals↗

[Adenoacanthoma].

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Adenocarcinoma↗

Freeze-fracture and immunohistochemical studies of gap junctions in human gastric mucosa with special reference to their relationship to gastric ulcer and gastric carcinoma.

Our aim was to determine whether the development of gap junctions in the human gastric mucosa has any relation to gastric ulcer and gastric carcinoma. Freeze-fracture replicas were prepared from the endoscopic biopsy specimens of 20 patients with gastric ulcer and 7 healthy volunteers. Large fractured areas of lateral cell membranes of surface mucous cells were examined randomly under an electron microscope. Small gap junctions were observed between gastric surface mucous cells in all healthy volunteers. Gap junctions in the patients with gastric ulcer were significantly fewer than in the healthy volunteers. In addition, gap junctions in patients with recurrent ulcer were significantly fewer than in those with first-onset ulcer. There was no obvious relationship between age and the development of gap junctions in patients with gastric ulcer or in healthy volunteers. In the areas of intestinal metaplasia, gap junctions were occasionally seen between absorptive cells of the villi, but not in the lateral membranes of goblet cells. Fresh frozen sections for indirect immunofluorescence were prepared from the endoscopic biopsy specimens of 19 patients with gastric ulcer and 5 patients with gastric cancer. Monoclonal antibody against liver gap junction protein (anti-connexin 32, 6-3G11) was used for the indirect immunofluorescence. On the border of gastric ulcer, fluorescent spots in the surface mucous cells were significantly fewer than in the surface mucous cells of the body and antrum which were distant from the ulcer area in the same patients. In gastric cancer tissue specimens, fluorescent spots were not observed at all.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Detection of Helicobacter pylori infection in early stage gastric cancer. A comparison between intestinal- and diffuse-type gastric adenocarcinomas.

BACKGROUND: Helicobacter pylori (H pylori) infection has been suggested to be a risk factor for gastric carcinogenesis. However, those previous studies have been concerned with advanced cancer cases. To the authors' knowledge, no detailed investigation on the prevalence of H pylori in early stage gastric cancer tissue has been performed. The relationship between early stage gastric cancer and the prevalence of H pylori was studied by a immunohistochemical staining analysis. METHODS: Sixty-eight patients who were endoscopically and surgically diagnosed as having early stage gastric cancer were enrolled in this study. All tissue specimens were obtained from patients by endoscopic biopsy, and were classified histopathologically as the intestinal-type of early stage gastric cancer in 34 patients (male-to-female ratio, 28:6; age, 64 +/- 11 years) and the diffuse-type of early stage gastric cancer (male-to-female ratio, 23:11; age, 57 +/- 14 years) in the other 34 patients. The amount of H pylori in tissue samples was graded from 0 (no characteristic bacteria) to 3 (numerous bacteria) using the fluorescent microscopic and an immunohistochemical technique. RESULTS: Twenty-nine of the 34 cases of the intestinal-type of gastric cancer had H pylori infection, as compared with 11 of the 34 cases of diffuse-type early stage gastric cancer. A significantly higher incidence (85%; P < 0.001) of H pylori infection and, thus, higher grading scores of the number of H pylori were found in the intestinal-type early stage gastric cancer. CONCLUSIONS: These findings suggest that the infection of H pylori may have a crucial relationship to the early stages of carcinogenesis of intestinal-type gastric cancer.

Adenocarcinoma↗

Evaluation of the effects of esophageal varicosclerosants on local vascular occlusion and systemic blood coagulation.

The efficacy and safety of the various sclerosants available for esophageal sclerotherapy have not been adequately investigated. In the present study, we experimentally evaluated the effects on local vascular occlusion and systemic blood coagulation of five sclerosants: 5% ethanolamine oleate, 99.5% ethanol, 2% aethoxysclerol, thrombin, and n-butyl-2-cyanoacrylate. The effects were tested after injection into the auricular vein of rabbits. Prothrombin time, activated partial thromboplastin time, plasma fibrinogen level, and peripheral blood platelet count were measured before injection and 5 minutes, 1 hour, 1 day, and 7 days later. Histologic examinations were then made of the auricular vein, lungs, liver, spleen, and kidneys. In the initial period after injection of ethanol or thrombin, fibrinogen level and platelet count were significantly reduced. Except for thrombin, none of the drugs affected prothrombin time or partial thromboplastin time. Local thrombosis took place after the injection of ethanolamine oleate, ethanol, and aethoxysclerol, whereas thrombin injection did not result in local thrombosis or vascular occlusion. Cyanoacrylate produced no local thrombus formation but caused vascular occlusion. Over-dosing of thrombin and ethanol led to sudden death of animals. These findings suggest that it is necessary to assess further the safety of intravascular use of thrombin, that the other drugs seem to be usable, and that careful consideration should be given to the excess use of ethanol in clinical settings. The present animal model may be useful for evaluating various sclerosants, although findings may not be applicable to humans because of differences in vascular size.

Animals↗

Using biopsy materials to detect mutations in gastrointestinal tumors.

Because endoscopic examinations are a crucial first step in the diagnosis of carcinomas, we have analyzed point mutations of the c-K-ras and p53 genes using biopsied samples. There is no previous report of such an approach, using only biopsied materials. We analyzed point mutations of the c-K-ras and p53 genes using 60 colorectal and 31 gastric tumor biopsy specimens. None of the gastric and seven of the colorectal tumors had mutations of the c-K-ras gene. p53 gene mutations were detected in six gastric carcinomas [two out of 11 intramucosal carcinomas (18.2%) and four out of 11 invasive carcinomas (36.4%)]. Eight of 15 invasive colorectal carcinomas (53.3%) showed point mutations in the p53 gene. Although point mutation frequencies in this study were relatively low when compared with previous reports in which surgical samples were used, our study shows that biopsied specimens are adequate and useful for analysis of gene point mutations.

Adenocarcinoma↗

Changes in bacterial phagocytosis of macrophages in experimental ulcerative colitis.

We previously reported that numerous macrophages which phagocytosed dextran sulfate sodium were observed to have accumulated in the mucosal lesions and in the spleen in experimental ulcerative colitis induced in mice with dextran sulfate sodium. In this paper, we investigated the bacterial phagocytic ability of macrophages which were isolated from spleens of mice treated with 3% dextran sulfate sodium for 6 months. In this model, the number of phagocytosed bacteria (Listeria monocytogenes) and the phagocytic index were significantly decreased. The phagocytic ability of splenic macrophages obtained from nontreated mice was also evaluated by incubating with dextran sulfate sodium in vitro, and adding bacteria. The number of phagocytosed bacteria and the phagocytic index were also significantly decreased. These observations suggest that the decrease in bacterial phagocytosis in this model by macrophages that phagocytosed dextran sulfate sodium indicates a decline of the mucosal defense system to bacteria.

Animals↗

Long-term ingestion of lactosucrose increases Bifidobacterium sp. in human fecal flora.

We investigated the influence of lactosucrose on the intestinal flora of healthy volunteers. Eight healthy volunteers (male:female = 4:4, age 34 +/- 4 years) received 6 g of lactosucrose daily for 8 weeks. Fecal microflora, bacterial metabolites, pH, and moisture were analyzed before and after the administration of lactosucrose. The results showed that the number and percentage of Bifidobacterium sp. in relation to the total bacteria significantly increased during the period of lactosucrose administration. Although fecal putrefactive products, fatty acids, pH, moisture content, and stool volume did not show significant changes during the test period, the amount of fecal phenol showed a negative correlation with the number of Bifidobacterium sp. Fecal ammonia significantly decreased after 4 and 8 weeks of lactosucrose administration, and 1 week after the end of lactosucrose administration, compared with results after a 1-week administration of lactosucrose. When the administration was stopped, the percentage of Bifidobacterium sp. in relation to the total count gradually decreased to the same level as before the administration of lactosucrose. These results suggest that under physiological conditions, lactosucrose acts on the intestinal microflora as a growth factor of Bifidobacterium sp.

Administration, Oral↗

Electron microscopic study of intercellular junctions in human gastric mucosa with special reference to their relationship to gastric ulcer.

The development of gap junctions in the human gastric mucosa has been examined to see if there is any relation to gastric ulcer. Freeze fracture replicas were prepared from the endoscopic biopsy specimens of 20 patients with gastric ulcer (15 men and five women, aged 49 (13) years) and seven healthy volunteers (four men and three women, aged 41 (19) years). Large fractured areas of lateral cell membranes of surface mucous cells were observed randomly at a direct magnification of 15,000 using electron microscopy. Small gap junctions were observed between gastric surface mucous cells in all healthy volunteers. Gap junctions in the patients with gastric ulcer were significantly fewer than in the healthy volunteers. In addition, gap junctions in patients with recurrent ulcer were significantly fewer than in those with first onset ulcer. There was no obvious relationship between age and the development of gap junctions in patients with gastric ulcer or in healthy volunteers. In areas of intestinal metaplasia, gap junctions were occasionally seen between absorptive cells of the villi, but not in the lateral membranes of goblet cells. These findings suggest that loss of intercellular communication via gap junctions is associated with gastric ulcer formation.

Female↗

Clinical evaluation of cardiac function by ambulatory ventricular scintigraphic monitoring (VEST): validation and study of the effects of nitroglycerin and nifedipine in patients with and without coronary artery disease.

Global left ventricular function and ECGs were continuously monitored by radionuclide ambulatory ventricular function monitoring (VEST) and validated against multigated blood pool analysis (MUGA) and left ventriculography in 26 subjects (study 1). Ejection fraction by VEST (Y) showed good correlation with Y = 5.5 +/- 0.79 X (r = 0.91), Y = 1.7 +/- 0.86 X' (r = 0.91), and Y = 11.6 + 0.68 X" (r = 0.82) to sitting and supine MUGA and left ventriculography, respectively. In study 2 left ventricular function and ECGs were evaluated at rest and during exercise without any drug (control), with nitroglycerin, and with nifedipine in 21 patients with coronary disease (group I) and six normal subjects (group II). In group I abnormal ejection fraction responses (exercise increase less than or equal to 6%) during the control exercise period were found in 15 patients (71%), ST segment abnormalities in seven (33%), and chest pain in four (18%). Control exercise increased end-diastolic volume (100 to 112 +/- 8%) and end-systolic volume (53 +/- 15% to 63 +/- 22%) and decreased the ejection fraction (47 +/- 15% to 43 +/- 21%). The ejection fraction during exercise increased after nitroglycerin (50 +/- 22%) or nifedipine (54 +/- 21%) (p less than 0.05). In group II the ejection fraction was unchanged between rest and exercise with or without nitroglycerin or nifedipine. Thus combined radionuclide and ECG monitoring by VEST could detect changes in left ventricular function at rest and during exercise over a prolonged period and demonstrated that nitroglycerin and nifedipine improved cardiac function in the ischemic setting with an increased ejection fraction in the upright position.

Coronary Disease↗

Occurrence of dysplasia and adenocarcinoma after experimental chronic ulcerative colitis in hamsters induced by dextran sulphate sodium.

In this study, long term dextran sulphate sodium administration was studied to ascertain whether colorectal carcinoma could be produced in patients with long standing ulcerative colitis. Simultaneously, changes in the intestinal microflora were analysed. Low grade to high grade dysplasia was seen in three of the five hamsters treated with 1% dextran sulphate sodium solution for 100 days, while no dysplasia was detected in the eight animals concomitantly treated with metronidazole, an antianerobic microbial agent, which prevents colonic ulceration. In these two groups, none of the animals developed colorectal cancer over 100 day period. In a group treated for 180 days, seven of the eight animals had dysplasia, and one had two adenomas. Furthermore, four of the eight animals had adenocarcinoma in the transverse colon; they were protruding well differentiated adenocarcinoma in one and non-protruding lesions infiltrating into the musclaris propria in three. The three non-protruding infiltrating adenocarcinomas were classified to be well differentiated adenocarcinoma in one and mucinous adenocarcinoma in two, resembling the type of cancer which complicates ulcerative colitis in man.

Adenocarcinoma↗