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Biomedical subjects

T Ohkusa

Publications and source records attributed to T Ohkusa.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Changes in endoscopic features and histological findings of H. pylori-related gastritis with a follow-up over a year after eradication of H. pylori].

This study reviews the cases of patients examined repeatedly by endoscopy with biopsies for over one year after eradication of H. pylori, measured according to the Sydney system. For 81 patients in whom H. pylori was successfully eradicated, the endoscopic features of edema, erythema, friability, exudate, erosion and rugal hypertrophy disappeared or diminished at 1-3 months after the therapy and endoscopic features of nodularity disappeared or diminished 12-15 months after the therapy. In these H. pylori-eradicated patients, the histological findings of inflammation and activity regressed 1-3 months after therapy, and atrophy and intestinal metaplasia regressed in 22(27%) and 28(35%) of the 81 patients examined 12-15 months after therapy. Regression of the atrophic pattern was observed in 38(47%) of these H. pylori-eradicated patients. In some H. pylori-eradicated patients, the regressions of atrophy and intestinal metaplasia were observed over one year after H. pylori eradication therapy. Inflammation and activity in the histological findings were related to the endoscopic findings of edema, erythema, friability, exudate, erosion and rugal hypertrophy.

Atrophy↗
PubMed1998

Disappearance of hyperplastic polyps in the stomach after eradication of Helicobacter pylori. A randomized, clinical trial.

BACKGROUND: Helicobacter pylori infection is common in patients with hyperplastic gastric polyps. OBJECTIVE: To study the effect of eradication of H. pylori on the clinical course of patients with hyperplastic gastric polyps. DESIGN: Single-blind, randomized, controlled trial. SETTING: University-based gastroenterology outpatient clinic. PATIENTS: 35 patients with H. pylori infection and hyperplastic gastric polyps at least 3 mm in diameter. INTERVENTION: Patients were randomly assigned to a treatment group (n = 17), which received a proton-pump inhibitor (omeprazole or lansoprazole), amoxicillin, and either clarithromycin or ecabet sodium, or to a control group (n = 18), which received no treatment. MEASUREMENTS: Patients underwent endoscopy before enrollment and 12 to 15 months after the end of treatment. Serum gastrin levels and titers of IgG to H. pylori were measured. RESULTS: In the treatment group, the polyps had disappeared by 3 to 15 months (average, 7.1 +/- 1.2 months) after the end of treatment in 12 of all 17 patients (71%) and in 12 of the 15 patients (80%) in whom H. pylori was eradicated. However, 12 to 15 months after the start of the study, no change in polyps or H. pylori status was seen in any controls (P < 0.001). Histologic findings of inflammation and activity, serum gastrin levels, and titers of IgG to H. pylori showed significant regression in the treatment group compared with the control group (P < 0.01). CONCLUSIONS: Most hyperplastic polyps disappeared after eradication of H. pylori. Thus, eradication should be attempted before endoscopic removal is done in patients with hyperplastic gastric polyps and H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Growth hormone preserves cardiac sarcoplasmic reticulum Ca2+ release channels (ryanodine receptors) and enhances cardiac function in cardiomyopathic hamsters.

OBJECTIVE: Growth hormone (GH) improves cardiac function in experimental models of heart failure and human dilated cardiomyopathy. However, the mechanism by which GH increases myocardial contractility is not entirely clear. Our aim was to examine the effects of GH on cardiac function and cardiac sarcoplasmic reticulum Ca2+ release channels (ryanodine receptors, RyR) in the hearts of UM-X7.1 cardiomyopathic hamsters during the development of heart failure. METHODS: Experimental and healthy control hamsters were examined at the age of 20 weeks. Recombinant human GH (2 mg/kg/day, s.c.) or vehicle was then administered for 3 weeks. We examined (i) the in vivo left ventricular (LV) size and LV systolic function using transthoracic echocardiography, (ii) the density (Bmax) and affinity (Kd) of high-affinity [3H] ryanodine binding sites in crude homogenates from normal and cardiomyopathic hamster hearts. RESULTS: Vehicle-treated UM-X7.1 hamsters exhibited significant increases in left ventricular end-diastolic diameter and end-systolic diameter (LVESd), and a significant decrease in LV fractional shortening (FS). GH-treatment attenuated the increase in LVESd and reduced the LV chamber size, and also significantly increased LVFS. Vehicle-treated UM-X7.1 hamsters exhibited a significantly lower Bmax than control hamsters (0.34 +/- 0.04 vs 0.44 +/- 0.06 pmol/mg, p < 0.05), and the treatment with GH in UM-X7.1 hamsters significantly attenuated the reduction of Bmax (0.42 +/- 0.03 pmol/mg vs vehicle-treated group (0.34 +/- 0.04 pmol/mg), p < 0.05). Kd did not differ significantly between the experimental groups. In normal control hamsters, GH treatment with this dose did not significantly enhance LV systolic function or the density of RyRs. There was no significant difference in terms of the connective-tissue volume-fraction, myocyte size and capillary density between the GH- and vehicle-treated groups of UM-X7.1 hamsters. CONCLUSIONS: GH treatment may improve cardiac function by preserving the density of RyRs and enhancing cellular function in cardiomyopathic hamster hearts.

Animals↗
PubMed1998

Prospective evaluation of a new anti-ulcer agent, ecabet sodium, for the treatment of Helicobacter pylori infection.

BACKGROUND: A new anti-ulcer agent, ecabet sodium, is active against Helicobacter pylori. AIM: To assess the efficacy of ecabet sodium for the eradication of H. pylori in patients with gastroduodenal diseases. METHODS: In a prospective, randomized and controlled study, patients infected with H. pylori were assigned to one of the following two groups: group LA, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. after meals for 2 weeks, and group LAE, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. + ecabet sodium 1000 mg b.d. after meals for 2 weeks. H. pylori status was determined before and at least 4 weeks after the therapy by rapid urease test, histology and a urea breath test. RESULTS: Of 101 patients (mean age 53 years, range 17-77 years, M/F: 68/33) enrolled in the study, 97 patients completed the protocol. Four patients were withdrawn because of diarrhoea (three from group LA) and skin rash (one from group LAE). The eradication of H. pylori was achieved in 28/48 (58%) patients in group LA and 38/49 (78%) patients in group LAE. The rate of eradication of H. pylori produced by the LAE treatment was significantly higher than that produced by the LA treatment. Side-effects appeared in two patients (malaise 1, skin rash 1) in group LAE and in seven patients (diarrhoea 6, dizziness 1) in group LA. These side effects disappeared spontaneously with cessation of the treatment. CONCLUSIONS: Ecabet sodium in combination with lansoprazole and amoxycillin increased the rate of eradication of H. pylori. Ecabet sodium appeared to reduce the incidence of diarrhoea as a side-effect of the dual LA therapy.

Abietanes↗
PubMed1998

Celiprolol, a beta-adrenoceptor antagonist with vasodilator effect, improves hemodynamic response to catecholamine, spontaneous locomotor activity, and survival in cardiomyopathic hamsters with advanced heart failure.

To assess the effects of celiprolol, which is a selective beta1-antagonist with vasodilating properties, on chronic heart failure in the cardiomyopathic hamster UM-X7.1 (CMH), we studied survival in treated CMH (celiprolol, 100 mg/kg/day) and untreated CMH. We also measured the hamsters' locomotor activity (by using an Automex system), in vivo left ventricular (LV) pressure with or without dobutamine infusion, and the myocardial beta-adrenergic-receptor density (Bmax), all at the age of approximately 210 days. Survival was significantly improved in the treated group compared with untreated group by 33.4% at the age of 210 days, and the median probabilities of survival were age 252 days in the treated group and 203 days in the untreated group (p < 0.01). The locomotor activity count was significantly higher in the treated group (14,945+/-6,895) than in the untreated group (8,264+/-2,945 counts/day; p < 0.05). The response of LV peak +/-dP/dt to dobutamine was significantly improved in the treated group by 22.9 and 34.8%, respectively, at 18 microg/kg/min. Bmax was also higher in the treated group than in the untreated group (80.1+/-15.1 vs. 65.2+/-10.6 fmol/mg; p < 0.05). This study suggests that long-term treatment with celiprolol could improve both survival and the hemodynamic responses to dobutamine, associated with the upregulation of beta-receptors, and increased locomotor activity.

Adrenergic beta-Agonists↗
PubMed1998

Effects of dantrolene sodium on progression of left ventricular hypertrophy induced by pressure overload in rats.

We studied the long-term effects of dantrolene sodium (D), a specific sarcoplasmic reticulum (SR) Ca2+-release inhibitor, on the progression of left ventricular pressure-overloaded hypertrophy in rats. We treated abdominal aorta-constricted rats with one of two doses of D for 4 weeks. The extent of hypertrophy was expressed as the ratio of left ventricle to body weight. Hemodynamic parameters were measured by using a microtip catheter manometer. Although a low dose of D (500 mg/L in drinking water) decreased blood pressure to normal levels, the progression of cardiac hypertrophy was not inhibited. In contrast, a high dose of D (5 mg/kg, i.p.) also reduced blood pressure and inhibited the progression of cardiac hypertrophy. Dantrolene sodium had no effect on cardiac function in sham-operated rats. Thus control of Ca2+ release from the SR might be crucial in regulating the progression of cardiac hypertrophy, the final mediator possibly being intracellular Ca2+ concentration.

Animals↗
PubMed1998

Polylysine-induced rapid Ca2+ release from cardiac sarcoplasmic reticulum.

The rapid kinetics of polylysine-induced Ca2+ release from cardiac sarcoplasmic reticulum (SR) was assessed in combination with its effect on ryanodine binding. SR vesicles were isolated from canine cardiac SR. The time course of SR Ca2+ release was continuously monitored by a stopped-flow apparatus, and [3H]ryanodine binding was done by using the filtration method. The initial rate of polylysine-induced Ca2+ release from cardiac SR revealed different concentration dependence from those observed in skeletal SR. The initial rate peaked at 0.11 microM, followed by a decrease at higher concentrations in skeletal SR, whereas it increased to 3.7 microM in cardiac SR. The [3H]ryanodine binding was also stimulated by polylysine with an identical parallelism with Ca2+ release in terms of polylysine concentration dependence. Thus we demonstrated that the cardiac SR Ca2+ release channel is sensitive to activation by polylysine and that there is a difference in the concentration dependence of polylysine-induced activation of cardiac and skeletal SR Ca2+ release channels.

Animals↗
PubMed1998

Alterations in cardiac SR Ca(2+)-release channels during development of heart failure in cardiomyopathic hamsters.

The cardiomyopathic Syrian hamster develops a progressive cardiomyopathy characterized by cellular necrosis, hypertrophy, cardiac dilatation, and congestive heart failure. This study aimed to identify alterations in cardiac mechanical function and in the cellular content of sarcoplasmic reticulum (SR) Ca(2+)-release channels (ryanodine receptors, RyR) in the heart of the UM-X7.1 cardiomyopathic hamster during the development of heart failure. Experimental and healthy control hamsters were examined at 8, 18, and 28 wk of age. The UM-X7.1 hamsters had developed left ventricular (LV) hypertrophy at 8 wk and a marked LV dilatation at 18-28 wk. During the latter stage, the UM-X7.1 hamster hearts showed global hypokinesis. Equilibrium binding assays of high-affinity sites for [3H]ryanodine were performed in ventricular homogenate preparations. There was no significant difference between the two groups in the maximum number of [3H]ryanodine binding sites (Bmax) at either 8 or 18 wk of age, although the cardiac pump function was impaired in UM-X7.1 hamsters at 18 wk of age. By 28 wk, Bmax was significantly lower in the UM-X7.1 hamsters. Quantitative immunoblot assay revealed that the content of RyR protein in cardiomyopathic hearts, which was increased at the early stage, declined to below normal as heart failure advanced. These results suggest that the number of RyR in the UM-X7.1 cardiomyopathic hamsters was preserved at both the hypertrophic and early stages of heart failure with a possibly compensatory increase in the level of protein expression, although the cardiac function already showed a tendency to be impaired.

Aging↗
PubMed1998

Relationship between fecal bile acids and the occurrence of colorectal neoplasia in experimental murine ulcerative colitis.

OBJECTIVE: The possible role of fecal bile acids in colorectal carcinogenesis in ulcerative colitis has been reported. In this study, we investigated the relationship between fecal bile acids and the occurrence of colorectal neoplasia in experimental murine colitis induced by dextran sulfate sodium. METHODS: Colorectal neoplasia in experimental colitis was induced by dextran sulfate sodium subsequent to a single azoxymethane pretreatment. Fecal bile acids were analyzed by gas-liquid chromatography. RESULTS: Multiple high-grade dysplasias (intramucosal adenocarcinoma) and inflammatory changes were seen in all mice administered dextran sulfate sodium and azoxymethane. Inflammatory changes were also observed in all mice given dextran sulfate sodium only, while neither tumor nor inflammatory changes were detected in any of the control mice. Significant increases in cholic acid were observed in the mice of the colorectal tumor and experimental colitis groups during the experimental period, while in the control mice, no significant changes in fecal bile acids were observed. CONCLUSION: It is suggested that fecal cholic acid and colitis may be intimately related to the development of colorectal neoplasia in this experimental model of murine colitis as well as in ulcerative colitis.

Adenocarcinoma↗
PubMed1997

Spontaneously colitic C3H/HeJBir mice demonstrate selective antibody reactivity to antigens of the enteric bacterial flora.

The idiopathic inflammatory bowel diseases, ulcerative colitis and Crohn's disease, are chronic disorders that appear to arise from an aberrant interaction of environmental, genetic, and immunologic factors. The aim of this study was to examine the immune reactivity of a spontaneously colitic mouse strain, C3H/HeJBir, to epithelial, food, and enteric bacterial Ags. Serum Ab responses of colitic C3H/HeJBir and noncolitic parental C3H/HeJ mice were measured by enhanced chemiluminescence Western blotting. No reactivity to epithelial or food Ags was detected. However, the sera from C3H/HeJBir mice had a reproducible banding pattern on Western blot to bacterial Ags, whereas sera from C3H/HeJ mice did not. Only a small, highly selected number of enteric bacterial Ags were recognized. There were major differences in the degree of recognition of different bacterial strains, marked by remarkably few Abs to Ags of the major anaerobes of the bacterial flora. The serum Abs detected on immunoblot were primarily IgG2a, suggesting a Th1 response. Comparison of sera reactivity to histopathologic severity showed an inverse relationship: one third of young C3H/HeJBir mice during the peak of colitis produced Abs to bacterial Ags, while later in life, when the colitis had resolved, 96% produced Abs. These data are consistent with an abnormal immune reactivity to enteric bacterial flora in C3H/HeJBir mice, a reactivity that is highly selective considering the abundant bacterial Ags present in the colon lumen. We postulate that this reactivity plays a role in the pathogenesis of colitis in these mice.

Animals↗
PubMed1997

Altered cardiac mechanism and sarcoplasmic reticulum function in pressure overload-induced cardiac hypertrophy in rats.

Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucial role in the regulation of intracellular Ca2+. Its functional properties are central to the excitation-contraction (E-C) cycle of cardiac muscle. In this study, we examined the hypothesis that alterations in SR function occur during the development of hypertrophy of the left ventricle (LV) induced in rats by pressure overload secondary to abdominal aortic coarctation. Ten days, 4 and 8 weeks after the operation, hemodynamic parameters were measured using a catheter-tip manometer. The SR vesicles of hypertrophic LV (group A) and sham-operated LV (group S) at each stage were used to study Ca2+ release and uptake, and to characterize the ryanodine receptor. Moderate hypertrophy was observed in group A even at the earliest stage. Systolic LV pressure and peak +dP/dt were significantly increased in group A. There were no significant change in diastolic LV pressure in either group at any stage. Hemodynamic data indicated that LV function in group A was enhanced during the development of the hypertrophy. The amount of Ca2+ release and uptake, and the number of ryanodine binding sites on the SR were higher in group A than in group S at both early and middle stages. However, 8 weeks after the operation, SR activity was normal, even though cardiac function was still augmented. Our results indicated that LV hypertrophy induced by pressure overload is associated with altered intracellular Ca2+ regulation, as reflected by the increased Ca2+ release and uptake functions of the SR and the quantitative change in the number of ryanodine receptors during the early stages of the development of hypertrophy. Therefore, alterations in the SR Ca2+ transport capacity could account, at least in part, for the alterations in E-C coupling seen in hypertrophy.

Adaptation, Physiological↗
PubMed1997

Early changes in the functions of cardiac sarcoplasmic reticulum in volume-overloaded cardiac hypertrophy in rats.

By sequestering activator calcium, the sarcoplasmic reticulum (SR) plays the central role in the excitation-contraction (E-C) cycle of cardiac muscle. Hence, functional changes in the SR in diseased myocardium might critically determine its mechanical characteristics. Previously, we demonstrated that both Ca2+ release and uptake were increased in SR isolated from hearts showing compensatory left ventricular (LV) hypertrophy taken from pressure-overloaded rats. However, it has not been elucidated whether such alterations also occur in the volume-overloaded myocardium. Rats in which volume-overloaded hypertrophy had been induced by aortocaval shunt 12 weeks prior to the investigation were compared to sham-operated controls in terms of SR Ca2+ uptake and release, and density of Ca2+ releasing channels (ryanodine receptors, RyR). Isometric tension and intracellular Ca2+ transients were also measured using the bioluminescent Ca2+ indicator, aequorin, in isolated LV papillary muscles. The extent of hypertrophy was verified by measuring the ratio of biventricular weight to body weight. In vivo, the aortocaval shunt rats showed normal LV contractility and slightly depressed LV relaxation, indicating a compensatory (adaptive) stage of LV function. In contrast, Ca2+ release, uptake, and maximal number of [3H]-ryanodine binding sites were all significantly lower in aortocaval shunt rats than in controls. Both the Ca2+ transients and isometric relaxation of the isolated myocardium were significantly prolonged in aortocaval shunt rats, though their amplitudes were similar in the two groups. Thus, the volume-overloaded cardiac hypertrophy, even at its hemodynamically compensatory (adaptive) stage, (i) was accompanied by abnormal Ca2+ handling, as indicated by prolonged intracellular Ca2+ transients and isometric tension traces, (ii) seems to involve subcellular mechanisms related to decreases in SR Ca2+ release and uptake functions, as well as to a decrease in the number of RyR. Therefore, changes in the intracellular processes underlying cardiac E-C coupling, including SR function, precede the development of this type of heart disease.

Animals↗
PubMed1997

Differences in sarcoplasmic reticulum gene expression in myocardium from patients undergoing cardiac surgery. Quantification of steady-state levels of messenger RNA using the reverse transcription-polymerase chain reaction.

Little is known about any alterations in sarcoplasmic reticulum (SR) gene expression associated with cardiac diseases of varying degrees of severity. We assessed, using the reverse transcription-polymerase chain reaction (RT-PCR) technique, SR Ca2+ transport protein gene expression in small tissue samples from failing hearts in patients undergoing cardiac surgery. Total RNA was extracted from 30- to 50-mg samples from the hearts of 13 patients with coronary artery disease, congenital heart disease, or valvular heart disease. We used RT-PCR to synthesize and amplify cDNA encoding cardiac SR Ca(2+)-ATPase, ryanodine receptor (RYR), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The amount of each mRNA in the sample was expressed relative to the amount of GAPDH mRNA. The expression level of each mRNA was correlated with the cardiac functional index. The mRNA levels for Ca(2+)-ATPase and RYR varied between heart samples, but showed a positive correlation with left ventricular ejection fraction. Ca(2+)-ATPase mRNA levels showed in inverse relationship with plasma brain natriuretic peptide. In addition, we isolated partial cDNA encoding a human cardiac RYR. The cDNA consisted of 487 nucleotides, and the nucleotide and deduced amino acid sequences showed 93% and 99% homology, respectively, to those of rabbit cardiac RYR. These results suggest that decreased levels of mRNA for SR Ca2+ transport protein could be related to abnormal cardiac function, regardless of the etiology of the heart disease. RT-PCR provides a rapid and economical way of quantifying the expression of multiple genes in small specimens and may, therefore, aid understanding of the pathophysiology and treatment of heart disease.

Adolescent↗
PubMed1997

Gastrointestinal autonomic nerve tumor with giant abscess. A case report and literature review.

We report a gastrointestinal autonomic nerve tumor of the stomach with a giant abscess. The patient had fever and pain and was found to have anemia and an abdominal mass. X-ray and endoscopic examination showed a gastric submucosal tumor with a fistula to the gastric lumen. Partial gastrectomy was performed and no metastasis was found. On gross examination, the excised tumor was seen to be a submucosal solid tumor with a giant abscess. Alpha streptococci and anaerobic gram-negative rods were cultured from the pus of the abscess. The tumor resembled a gastric myogenic tumor composed of spindle cells, partly showing storiform and epithelioids. Tumor cells showed positive staining for vimentin and neuron-specific enolase but were negative for desmin, alpha-smooth muscle actin, and S-100 protein. Ultrastructural examination showed remarkable interdigitation of cytoplasmic processes with neurosecretory granules between the tumor cells. This lesion was similar to previously described gastrointestinal autonomic nerve tumors. Gastrointestinal autonomic nerve tumors are a rare, distinct subtype of gastrointestinal stromal tumors; although several cases of focally necrotic tumors have been reported, there has been only one report of the tumor with an abscess, as in our case.

Abscess↗
PubMed1997

Changes in serum pepsinogen, gastrin, and immunoglobulin G antibody titers in helicobacter pylori-positive gastric ulcer after eradication of infection.

There are no studies of changes in immunoglobulin G (IgG) titers to Helicobacter pylori, serum pepsinogen, and gastrin in patients with H. pylori-positive gastric ulcers. We investigated the effect of therapy for H. pylori-positive gastric ulcer on IgG titers to H. pylori, serum pepsinogen I and II, and gastrin. Thirty-six patients with H. pylori-positive gastric ulcer were treated with lansorazole and antibiotics for 2 weeks. Serum pepsinogen I and II concentrations, serum gastrin, and IgG titers to H. pylori were measured before treatment and then at 4 and 12 weeks after stopping the treatment. The presence or eradication of H. pylori was determined using the rapid urease test and by histologic H. pylori staining. For 19 patients in whom H. pylori had been successfully eradicated, the pepsinogen I/II ratio increased, pepsinogen II levels decreased, and the anti-H. pylori IgG decreased compared with the results from before therapy and with those from 4 and 12 weeks after therapy. Gastrin levels decreased compared with pretreatment results and those from 4 weeks after the end of treatment. In 17 patients in whom the therapy failed to eradicate H. pylori infection, there were no sequential significant changes in the pepsinogen I/II ratio or in the levels of pepsinogen I, pepsinogen II, anti-H. pylori IgG, and gastrin. A decrease in the serum levels of the IgG antibody to H. pylori and gastrin and also an increase in the pepsinogen I/II ratio could be used as predictors for the eradication of H. pylori infection in gastric ulcer.

Aged↗
PubMed1997

Comparison of necrosis and fibrotic repair after ethanol injection between normal and cirrhotic livers.

To study the effects of percutaneous ethanol injection therapy on livers, we investigated necrotic changes after ethanol injection and fibrotic changes during the repair process in cirrhotic livers in comparison with normal livers. Male rats were treated with oral doses of 3'-methyl-4-dimethylaminoazobenzene and thioacetamide to produce liver cirrhosis. Both control animals and cirrhotic animals were injected with 0.2 ml of absolute ethanol into livers. Histological samples were cut serially, and the maximum areas of necrosis and fibrosis were measured until 28 days after the injection. Although the maximum area of necrosis was not different between cirrhotic livers and control livers, the average fibrotic ratio [(maximum fibrotic area/maximum necrotic area + maximum fibrotic area) x 100] was 64% in control livers (n = 9) and 40% in cirrhotic livers (n = 9; p < 0.05). The fibrotic repair process after ethanol injection seems to be impaired in cirrhotic livers as compared with normal livers.

Animals↗