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Biomedical subjects

T Aoyagi

Publications and source records attributed to T Aoyagi.

At least 199 records · Page 11Linked to original sources

[Helicobacter pylori and urease activity--comparative study between urease positive and negative mutant strains].

The ammonia concentration in the gastric juice from H. pylori positive cases was significantly higher than that from negative cases, and there was positive correlation between number of H. pylori, gastritis score and ammonia concentration in gastric juice. It is suggested that ammonia in gastric juice which is produced by powerful urease activity of H. pylori is one of the pathogenic factors in gastritis. We succeeded in producing a urease-negative mutant strain of H. pylori. This strain did not colonize gastric mucosa of Cynomolgus monkeys. H. pylori survival time in vitro was increased at pH 2.0 in the presence of urea. These results suggest that urease facilitates colonization of gastric mucosa by H. pylori, and prolongs the survival of H. pylori in an acidic environment.

Ammonia↗

[Helicobacter pylori and the development of atrophic gastritis].

A close relationship between H. pylori infection and atrophic gastritis has been reported, and atrophic gastritis has been thought of as one of the precursors of gastric carcinoma. It was reported that there was a significant positive correlation between the reduction of serum pepsinogen (PG) I/II ratio and the progression of atrophic gastritis. The ratio of PG I/II was significantly decreased in H. pylori positive patients when compared to H. pylori negative patients with chronic gastritis. The PG I/II ratio in gastric cancer was significantly lower than that of chronic gastritis, while the prevalence of H. pylori was not significant difference between gastric carcinoma and chronic gastritis. It is suggested that there is strong correlation between H. pylori infection and the development of atrophic gastritis, and that eradication of H. pylori from gastric mucosa might reduce the risk of developing gastric carcinoma.

Adult↗

[Progress in management for heart failure: diuretics].

In congestive heart failure (CHF), a variety of compensatory mechanisms such as activation of sympathetic nervous system, renin-angiotensin system and vasopressin, facilitate water and sodium retention and increase circulating blood volume, which primarily improve systemic perfusion. However, hypervolemia sometimes induces pulmonary edema and afterload elevation, resulting in a further decrease in cardiac output. Diuretics are administered in patients with CHF to cut this vicious cycle by reducing blood volume. Evaluation of hemodynamic states is important in patients with severe CHF, since an excessive reduction in preload could critically decrease cardiac output. Among conventional diuretics, loop diuretics is the most potent and widely used for management of CHF. Inhibition of such compensatory mechanisms such as angiotensin-converting enzyme inhibitors and atrial natriuretic peptide-related agents is shown to exert natriuretic and desirable hemodynamic effects in CHF and is among candidates for future diuretics.

Angiotensin-Converting Enzyme Inhibitors↗

[Current therapy of obstructive jaundice due to cholelithiasis].

On recent development of apparatus and techniques of ultrasonography and endoscopy we prefer to try the following procedures for removing jaundice instead of surgical operation: 1) Percutaneous Transhepatic Biliary Drainage (PTBD) 2) Endoscopic Retrograde Biliary Drainage (ERBD) 3) Endoscopic Naso-Biliary Drainage (ENBD) 4) Endoscopic Sphincterotomy (EST). After removing the jaundice and inflammation of bile duct, we try following procedures for elimination of gallstone: 1) endoscopic mechanical lithotripter (EML) 2) (Extracorporeal shock wave lithotripsy (ESWL) And we have got the excellent results.

Aged↗

[Clinical features of the lung diseases due to Mycobacterium avium and M. intracellulare].

In recent years, it has been made easy to identify Mycobacterium avium and M. intracellulare by DNA-probe test. To evaluate possible clinical differences between the lung diseases due to M. avium and those due to M. intracellulare, we studied a total of 248 cases (136 due to M. avium and 112 due to M. intracellulare). M. avium cases were found more frequently in the eastern part of Japan, whereas M. intracellulare cases were seen more frequently in the western part of Japan. There was no significant difference between M. avium cases and M. intracellulare cases in sex, age, complications, chief complaint, body weight, tuberculin skin test, erythrocyte sedimentation rate, serum protein content, findings of chest X ray. M. avium cases were more frequently detected by health examination. M. avium was more susceptible to cycloserine than M. intracellulare. On the other hand, M. intracellulare was more susceptible to streptomycin and kanamycin. The prognosis of M. intracellulare cases were better than M. avium cases, when compared only the patients who showed positive tuberculin skin test.

Adult↗

Deficiency of fibrinolytic enzyme activities in the serum of patients with Alzheimer-type dementia.

Previously we reported that there is a kallikrein deficiency in the cerebral tissue of patients with Alzheimer-type dementia. The present study was performed to investigate protease changes in the serum of these patients. The results showed that the kallikrein activity was normal, but that the activities of plasmin and urokinase were significantly low. The present findings indicate a derangement in the clotting and fibrinolytic systems in Alzheimer patients.

Aged↗

Induction of hepatic microsomal cytochrome P450 and drug-metabolizing enzymes by 4-benzylpyridine and its structurally related compounds in rats. Dose- and sex-related differential induction of cytochrome P450 species.

We examined the abilities of 4-, 3- and 2-benzylpyridine and 4-tert-butylpyridine to induce hepatic microsomal cytochrome P450 and drug-metabolizing enzymes in male and female rats in order to define the effects of pyridine-containing compounds on drug metabolism. 4-Benzylpyridine (0.4 mmol/kg, for 2 consecutive days) induced total cytochrome P450 to about three times that of the controls at 24 hr, and its inducing effect was sustained for 120 hr after the treatment in male and female rats. 4-Benzylpyridine was a more potent inducer of cytochrome P450 than 3- and 2-benzylpyridine, which induced the cytochrome to 71.4 and 43.9%, respectively, of that produced by the 4-substituted isomer. 4-tert-Butylpyridine also induced cytochrome P450. Immunoblot analysis revealed that a single treatment of male rats with 4-benzylpyridine at doses ranging from 0.05 to 0.80 mmol/kg induced cytochrome P450b/e and caused a maximum increase in the level of the isozyme at the 0.2 mmol/kg dose. 4-Benzylpyridine at doses from 0.40 to 0.80 mmol/kg also induced cytochrome P450c/d in male rats. In female rats, 4-benzylpyridine induced cytochrome P450b at doses ranging from 0.1 to 0.80 mmol/kg and produced a maximum increase in the level of this isozyme at 0.40 to 0.60 mmol/kg. Induction of cytochrome P450c/d by 4-benzylpyridine in female rats was observed at a dose of 0.20 mmol/kg, and the magnitude of the induction of the isozyme was increased in a dose-dependent manner. Both 3- and 2-benzylpyridine induced cytochrome P450b/e and/or c/d depending on the increase of total cytochrome P450 without changing the induction patterns of the isozymes. 4-tert-Butylpyridine induced cytochrome P450b at doses ranging from 0.20 to 0.60 mmol/kg and slightly induced P450c/d at doses ranging from 0.10 to 0.40 mmol/kg in male rats. These results and our previous report (Matsuura et al., Biochem Pharmacol 41: 1949-1956, 1991) clearly show that the pyridine compounds having lipophilic groups at the 4- or 3-position of the ring could be inducers of cytochrome P450. The present results also revealed that 4-benzylpyridine shows dose- and sex-related differences in the induction of cytochrome P450b/e and c/d in rats.

Aminopyrine N-Demethylase↗

The prevalence and prognostic significance of arrhythmias in Duchenne type muscular dystrophy.

To investigate the prevalence and prognostic significance of cardiac arrhythmias in Duchenne type muscular dystrophy 24-hour ambulatory ECG was performed in 80 patients with Duchenne type muscular dystrophy, and they were followed up for 5 years. Various arrhythmias were observed in 63.8% (51 of 80) of the patients. Ventricular premature beats were found in 30% (24 of 80), and the incidence of ventricular premature beats increased as the clinical severity of skeletal muscle involvement advanced. Forty-seven patients survived for 5 years, but the incidence of arrhythmias increased from 38.3% (18 of 47) to 74.5% (35 of 47) (p < 0.001). During the 5-year period, four of 33 deaths were sudden. Malignant ventricular premature beats (ventricular couplets, ventricular tachycardia, and R-on-T-type ventricular premature beats) were observed in three of these four patients. It appears that cardiac arrhythmias are a common complication of Duchenne type muscular dystrophy and that the incidence of ventricular arrhythmias increases with the progression of myocardial involvement. There is an association between ventricular arrhythmias and sudden death, but the reduction of ventricular arrhythmias may not reduce the incidence of episodes of sudden death.

Adolescent↗

Suppression of experimental autoimmune myasthenia gravis with new immunosuppressants: 15-deoxyspergualin and actinobolin.

In the search for a new drug to treat myasthenia gravis, we studied the efficacy of new immunosuppressants on experimental autoimmune myasthenia gravis (EAMG). 15-Deoxyspergualin (15-DSP), bactobolin and actinobolin were administered to some groups at the time of immunization and to other groups 10 days after. The most effective results were achieved with doses of 2.5 mg/kg daily of 15-DSP and 30 mg/kg daily of actinobolin administered from day 1. In both groups, the body weights of the rats increased as normally as those of controls and signs of myasthenia were mild. Immunoelectron microscopic examination of the neuromuscular junctions in rats treated with 2.5 mg/kg of 15-DSP appeared normal, even in the chronic phase (induced by a booster at week 4). Levels of anti-acetylcholine receptor antibodies were almost completely suppressed. Although the effects of these drugs were more remarkable when administered from day 1 than from day 10, the results suggest that they may prove useful in treating myasthenic patients.

Animals↗

Direct and indirect effects of Porphyromonas gingivalis lipopolysaccharide on interleukin-6 production by human gingival fibroblasts.

We examined the production of interleukin-6 (IL-6) by human gingival fibroblasts (ATCC CRL 1292) stimulated with lipopolysaccharide (LPS) from Porphyromonas gingivalis and Escherichia coli, or supernatant of human peripheral blood adherent cell culture medium incubated in the presence of IL-1 and the same two LPS. Confluent monolayers of gingival fibroblasts were incubated with stimulants for 6 h at 37 degrees C in 5% CO2 and air. After removal of stimulants, the cell cultures were incubated for an additional 2 or 24 h in the same environment. At the end of the culture period, supernatants were collected and assayed for IL-6 activity by stimulatory IgG production with the human B-lymphoblastoid cell line CESS. The direct effect of LPS on IL-6 production by gingival fibroblasts was much weaker than the indirect one via IL-1 production by adherent cells. The stimulating effect of culture supernatants of adherent cells stimulated with LPS on IL-6 production by gingival fibroblasts was as effective as that of recombinant IL-1, when this latter was added at a concentration equivalent to that contained in the culture supernatant of adherent cells. These results suggest that, although gingival fibroblasts may be involved in the pathogenesis of chronic periodontal disease by the production of cytokines, such a role may not result from a direct stimulation by periodontopathic bacteria. The phenomenon is more likely to be mediated indirectly by IL-1 produced by infiltrating inflammatory cells.

Analysis of Variance↗

Myocardial function in immature and mature sheep with pressure-overload hypertrophy.

The effect of pressure-overload left ventricular hypertrophy (LVH) on myocardial function is controversial. A major factor in the controversy may be the age at which the pressure overload was induced. The goal of this study was to determine whether the age at which the LVH was induced affected systolic myocardial function. We studied lambs (n = 8) and sheep (n = 7) with LVH induced by constricting the ascending aorta and their sham-operated controls (n = 7 and n = 7). This new, unsedated, ovine model of LVH was large enough to accommodate chronic surgical implantation of instrumentation and the induction of pressure-overload hypertrophy in both young and adult age groups. Solid-state intraventricular pressure transducers and sonomicrometer crystal were used to assess instantaneous left ventricular pressure and dimensions. Myocardial contractility was assessed with midwall shortening at common preload and afterload. Load alterations were induced by graded infusion of methoxamine. There was depressed myocardial function in adult sheep with LVH compared with adult controls. Lambs with and without LVH had normal left ventricular myocardial function, similar to adult controls. Similar results were obtained in studies after beta-adrenergic receptor blockade. We conclude that maturation decreases the ability of the myocardium to maintain normal contractility in the presence of pressure-overload hypertrophy.

Adrenergic beta-Antagonists↗

Different responses of extent and velocity of contraction to dobutamine in conscious sheep.

The shortening- and shortening rate-preload-afterload relations, based on the concept of the myocardial end-systolic stress-strain relation (ESSSR), are a newly developed load- and size-independent assessment of myocardial contractility. The purpose of this study was to apply this assessment to compare extent and velocity of myocardial contraction during graded infusions of dobutamine. Seven chronically instrumented unsedated sheep were studied at rest and during graded infusions of dobutamine (2.5-20 micrograms.kg-1.min-1). The ESSSR were linear over a wide range of load alterations, whereas the end-systolic pressure-diameter relations (ESPDR) were generally nonlinear. Midwall shortening rate (SRm) at common preload and afterload representing contraction extent increased with each dose of dobutamine through 20 micrograms.kg-1.min-1. In contrast, midwall shortening (Sm) increased through dobutamine 5 micrograms.kg-1.min-1 but not at higher dobutamine infusion rates. Conventional endocardial shortening and the slope of the ESPDR, fitted to a linear model, exhibited responses similar to Sm. The velocity of circumferential endocardial fiber shortening (Vcf,c), Vcf,c-afterload relation, and maximum first derivative of left ventricular pressure exhibited responses similar to SRm. Thus both the extent and velocity of contraction increased at low doses of dobutamine, whereas only the velocity increased at high doses. Potential mechanisms for the saturated response of the extent of contraction include 1) shorter systolic time for contraction due to earlier onset of relaxation and 2) the utilization of myocardial contractile energy for left ventricular wall deformation at small cavity volumes at high doses of dobutamine.

Animals↗

Dose-dependent enzyme suppression in spleen induced by GM1 (monosialoganglioside 1) administration to mice.

Our previous studies suggested that the administration of exogenous gangliosides to the body modulates enzymatic networks in the brain. In the present study, we tested whether that is the case with another organ, spleen. By testing the dose response relationship, we found that there is a optimum dose for the effect of enzymatic modulation of GM1 (monosialoganglioside 1) administration. Although the optimum level varied depending on each of the examined hydrolytic enzymes, it usually fell in the range around 50 micrograms/kg body weight. The findings led us to conclude that the enzyme-modulating actions of gangliosides come not merely from the bizarre actions in vivo of high molecular exogenous substances.

Animals↗

Preparations of cyclic sulfoxide derivatives and their evaluation as transdermal penetration enhancers.

Novel cyclic sulfoxides, such as 2-octyl, 2-dodecyl and 2-hexadecyltetrahydrothiophene-1-oxide were prepared by the alkylation of tetrahydrothiophene-1-oxide. Additionally, 2-methyl, 2-ethyl and 2-propyl-5-dodecyltetrahydro-thiophene-1-oxide were conducted by further alkylation. Their enhancing activity on the penetration of indomethacin through rabbit skin was evaluated in in vitro experiments, and the effect of the alkyl length on the enhancing activity was discussed. Among the 2-alkyl-tetrahydrothiophene-1-oxides, the compounds containing dodecyl and hexadecyl groups promoted a much greater penetration of the drug through the skin than the compound containing an octyl group. A stronger effect was observed in the experiment using 2-dodecyl-5-alkyltetrahydrothiophene-1-oxide, as compared with the that of 2-dodecyl-tetrahydrothiophene-1-oxide. The substitution of the alkyl groups to the next position of the sulfoxide group seemed to make the enhancing activities large.

Animals↗

Benarthin: a new inhibitor of pyroglutamyl peptidase. I. Taxonomy, fermentation, isolation and biological activities.

We found benarthin, a new inhibitor of pyroglutamyl peptidase, in the fermentation broth of Streptomyces xanthophaeus MJ244-SF1. It was purified by column chromatography and centrifugal partition chromatography (CPC) and then was isolated as a colorless powder. The binding of benarthin was competitive with substrate and its inhibition constant (Ki) was 1.2 x 10(-6) M.

Classification↗