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H Tsutsui

Publications and source records attributed to H Tsutsui.

At least 145 records · Page 8Linked to original sources
PubMed1993

[Trend of molecular biological studies on the liver sinusoidal cells--Kupffer cells].

The Kupffer cells are sessile macrophages residing in the hepatic sinusoids. The Kupffer cells are well known as the first line of defence against pathogenic agents derived from not-self substances, in some cases even from self proteins. Indeed, Kupffer cells play an important roles in such a defence system: they act as an antigen presenting cells, and also produce various kinds of cytokines and chemical mediators such as prostaglandins, leukotrienes and platelet activating factor. In this article, we introduce these functions of Kupffer cells and discuss the possible pathway of the signal transduction.

Animals↗
PubMed1992

Drug-specific T cells derived from patients with drug-induced allergic hepatitis.

Drug-induced allergic hepatitis is a tissue-specific inflammatory disease caused by hypersensitivity to a particular drug. Although the frequency of drug-induced allergic hepatitis appears to increase in proportion to the medicine, the mechanism by which tissue specificity is determined is still to be elucidated. In this study, we established CD4+ T cell clones specific for particular drugs from patients with drug-induced allergic hepatitis accompanied with mild blood eosinophilia and analyzed the possible role of liver protein as a directing factor of liver-specific inflammatory reactions. All CD4+ T cell clones obtained from two patients with this disease proliferated in response to a combination of the particular drug plus liver specific protein (LSP), which consists of over 30 proteins. Some T cell clones were responsive to an antigenic conformation consisting of the 200-kDa glycoprotein (partly purified LSP), a component of LSP, plus the causal drug. In contrast, all CD4+ T cell clones from a patient with simple drug-induced eosinophilia responded to the causal drug in the absence of LSP and partly purified LSP. These data suggested that LSP or partly purified LSP of the appropriate Ag is the target that leads to liver-specific inflammation in drug-induced allergic hepatitis. Furthermore, T cell lines derived from patients with drug-induced allergic hepatitis and simple drug-induced eosinophilia produced large amounts of IL-5 after the appropriate antigenic stimulation, whereas CD4+ T cell clones from donors with a normal amount of peripheral blood eosinophils secreted a much less IL-5. Taken together, these results indicate that overproduction of IL-5 by the allergen-sensitized T cells may result in blood eosinophilia.

Adult↗
PubMed1992

Long-term haemodynamic effects of a 4-week regimen of nipradilol, a new beta-blocker with nitrovasodilating properties, in patients with portal hypertension due to cirrhosis. A comparative study with propranolol.

To study the long-term effects of pharmacological combination therapy, a comparison was made of the haemodynamic changes in patients with cirrhosis and portal hypertension following a 4-week treatment of propranolol or nipradilol, a new nonselective beta-blocker with nitrovasodilating effect. Nipradilol (12 mg/dag, n = 12) significantly diminished wedged hepatic venous pressure (WHVP, 25 +/- 16%), the hepatic venous pressure gradient (HVPG, 20 +/- 12%), and estimated hepatic blood flow (EHBF, 18 +/- 16%). Propranolol (30 mg/day, n = 11) also caused a significant reduction in WHVP (22 +/- 21%) and HVPG (24 +/- 21%), but not in EHBF. The percentage of portal pressure reduction and the frequency of nonresponders did not differ between the nipradilol and propranolol groups. Both agents reduced heart rate by approx. 20%. Nipradilol, however, did not cause a significant reduction in cardiac index (CI) versus a 14% reduction by propranolol. Pulmonary capillary wedge pressure and central venous pressure, an index of preload, were decreased slightly in the nipradilol group. When nonresponders were excluded, there was a significant correlation of the percentage of reduction between WHVP and CI or systemic vascular resistance, in the nipradilol group. These results indicate that nipradilol may have potent hypotensive effects on portal hypertension, similar but not superior to propranolol. Nipradilol, at the dosage used in the present study, did not appear to exert a nitrovasodilating effect to enhance the portal pressure reduction induced by beta-blocking action.

Adrenergic beta-Antagonists↗
PubMed1992

Endothelin stimulates multiple responses in isolated adult ventricular cardiac myocytes.

We have examined the responses to endothelin (ET) in isolated adult cardiac myocytes from both rodent and feline species to assess whether endothelin may have a role in the induction or mediation of cardiac hypertrophy in the adult animal. We have evidence that ET acts by more than one mechanism to promote cell-signaling events believed important in growth regulation. In isolated adult cardiac ventricular myocytes labeled overnight with [3H]inositol, endothelin (ET) promoted a two- to fourfold increase in the accumulation of inositol polyphosphates in a dose-dependent manner with an half-maximal effective concentration (EC50) of approximately 5 nM. In contrast, picomolar concentrations of ET promoted an increase in both the extent and velocity of sarcomere shortening in electrically stimulated myocytes. Pretreatment of cells with pertussis toxin had no effect on the ET-stimulated phosphoinositide hydrolysis, but blocked the ET-stimulated positive inotropic effect. In addition to these early responses to ET, results obtained by Northern blot analysis demonstrate that exposure of isolated cardiac myocytes to 100 nM ET promoted the expression of c-fos and c-zif in both mammalian species. These data demonstrate that ET stimulates multiple cell-signaling pathways in adult mammalian cardiac myocytes. A paracrine mechanism of regulation of adult myocardium is suggested.

Animals↗
PubMed1992

Alcohol-induced sinus bradycardia and hypotension in patients with syncope.

We observed 2 cases of repeated episodes of syncope after alcohol ingestion. Both patients were light drinkers and had carotid sinus hypersensitivity. In both cases, alcohol loading tests repeatedly induced sinus bradycardia and hypotension 1.0-1.5 hours after drinking alcohol. Atropine was effective in improving symptoms. A loading test using a glucose solution of equivalent osmolarity and volume was negative. Acute alcohol ingestion usually increases heart rate with variable effects on blood pressure. However, our 2 cases exhibited unusual alcohol-induced sinus bradycardia and hypotension, suggesting a paradoxical increase in parasympathetic activity and/or decrease in sympathetic activity.

Aged↗
PubMed1992

Left ventricular mechanics and myocyte function after correction of experimental chronic mitral regurgitation by combined mitral valve replacement and preservation of the native mitral valve apparatus.

BACKGROUND: Contractile function improves after correction of experimental mitral regurgitation, but ejection performance becomes depressed when mitral valve replacement involves chordal transection. A role for chordal transection in producing the depressed ejection performance was suspected but uncertain. Therefore, in this study, we tested two specific hypotheses: 1) that contractile function would improve and, in conjunction with chordal preservation, would allow for preserved ejection performance and 2) that improved left ventricular contractile function after surgery would be reflected in the function of myocytes isolated from the affected left ventricles. METHODS AND RESULTS: We examined ventricular contractile function and ejection performance and isolated myocyte function after correction of experimental mitral regurgitation (chordal rupture) with mitral valve replacement that involved chordal preservation. After 3 months of chronic mitral regurgitation, the average regurgitant fraction of seven dogs was 0.77 +/- 0.04. End-diastolic volume had increased from 79 +/- 5 to 132 +/- 10 cm3 (p < 0.05). At that time, all indexes of left ventricular contractile function were depressed. Three months after mitral valve replacement with chordal preservation, end-diastolic volume fell to 100 +/- 4 cm3 (p < 0.05). At this time, all indexes of contractile function had returned to normal. End-systolic stress and ejection fraction after mitral valve replacement were similar to their baseline levels. Viscosity-velocity curves (analogous to force-velocity curves) of myocytes isolated from the affected left ventricles were similar to those of myocytes isolated from normal left ventricles. CONCLUSIONS: We conclude that mitral valve replacement with chordal preservation allows ventricular contractile function to return to normal. Normal global ventricular function, in turn, is associated with normal function of the individual myocytes that compose the left ventricular chamber. Further, chordal preservation allowed for loading and ejection performance to return to premorbid levels.

Animals↗
PubMed1992

Importance of direct hepatocytolysis by liver macrophages in experimental fulminant hepatitis.

When lipopolysaccharide was administered to mice that had been injected with heat-killed Propionibacterium acnes, most of them died of massive liver necrosis. Previously, we demonstrated that a soluble hepatocytotoxic factor released by liver adherent cells fully activated by both P. acnes and lipopolysaccharide was attributable to the late stage of this severe liver injury. In this report, we focused on the hepatocytolysis by these liver adherent cells in a cell-cell interaction manner. Shortly after stimulation with lipopolysaccharide, the P. acnes-elicited liver adherent cells almost completely killed the hepatocytes prepared from both normal syngeneic mice and P. acnes-treated ones. Since P. acnes-elicited liver adherent cells also proved to produce various kinds of cytokines in a short time, the role of cytokines in this liver injury was analyzed. Only TNF-alpha enabled the P. acnes-elicited liver adherent cells to kill hepatocytes prepared from the same mice, but none from the normal ones. These results suggest that the liver adherent cells accumulated and partly stimulated by P. acnes-treatment might rapidly lyse the autologous hepatocytes once triggered by lipopolysaccharide and that the TNF-alpha these liver adherent cells produced might upregulate their own hepatocytotoxic ability.

Acute Disease↗
PubMed1992

Transtrochanteric anterior rotational osteotomy for idiopathic and steroid-induced necrosis of the femoral head. Indications and long-term results.

From 1972 until 1988, transtrochanteric rotational osteotomy was used to treat 474 hips in 378 patients with idiopathic and steroid-induced osteonecrosis of the femoral head. Two hundred twenty-nine of 295 hips with anterior rotation and follow-up periods ranging from three to 16 years had excellent surgical results (success rate, 78%). Outcome was chiefly dependent on the ratio of transposed intact posterior articular surface to the acetabular weight-bearing area after osteotomy. This relationship suggested that the transposed intact area should occupy more than 36% of the acetabular weight-bearing area by adequate rotation and intentional varus position in addition to rotation, especially for extensive lesions. Salvage operations, such as total hip arthroplasty, were performed on 18 hips, of which ten hips were cases of either relative indication for extensive lesions in young patients or other misindications for rotational osteotomy. Four hips sustained neck fracture, including three hips after 180 degrees of posterior rotation; two hips were complicated with avascular necrosis, and another two hips developed osteoarthrosis. Histologically, femoral heads with osteoarthrosis removed at the time of salvage operation showed complete healing of the necrotic lesion. The overall findings indicate that healing of the necrotic lesion of the femoral head may be brought about by rotational osteotomy if it spares the vulnerable site from the brunt of mechanical stress.

Acetabulum↗
PubMed1992

[Choleretic effects of taurine on experimentally-induced intrahepatic cholestasis].

When a lymphokine, the cholestatic factor, is intravenously injected into rats through a mesenteric vein, remarkable reductions in bile flow and bile acid excretion are observed. However when taurine was injected with the cholestatic factor, the reduction in bile flow and bile acid excretion were significantly suppressed. Moreover, injection of taurine with cholestatic factor resulted in the decreases of both bile acid-dependent bile flow and vesicular transport but not bile acid-independent bile flow. Not significant choleretic effects were noted when taurine alone was administered to normal rats.

Animals↗
PubMed1991

Effect of gomisin A in the prevention of acute hepatic failure induction.

Nearly all rats develop massive hepatic cell necrosis and die upon intravenous administration of heat-killed Propionibacterium acnes followed by a small amount of Gram-negative lipopolysaccharide 7 days later. However, when such an experimental liver disorder is induced in rats raised for 4 or more weeks on food containing 0.06% of gomisin A extracted and purified from Schizandra chinensis, the survival rate rises, histological changes of the liver improve remarkably, and splenocyte reactivity to phytohemagglutinin and pokeweed mitogen as well as splenocyte interleukin 1 productivity are retained. These results suggested the possibility that the development of acute hepatic failure may be prevented with the oral administration of gomisin A.

Animals↗
PubMed1991

Crystal structure of Streptomyces erythraeus trypsin at 2.7 A resolution.

The crystal structure of Streptomyces erythraeus trypsin (abbreviated as SET) has been determined in order to clarify the precise structure of the vicinity of the active site of serine protease and to understand its structure-function relationship. Crystals of SET were prepared at its active pH range (pH 5-10) without any inhibitors which might have affected the circumstances around the active sites. The structure model of SET was made based on the electron density map obtained by the multiple isomorphous replacement method at 3.5 A resolution, and refined by the restrained least-squares method. The current model yields a crystallographic R-factor of 0.272 for 4,968 reflections between 8 and 2.7 A resolution. Though the sequence homology among SET, Streptomyces griseus trypsin and bovine trypsin, 32-37%, is not so high, their overall structures are similar to each other. Comparison of the three molecular structures shows that: 1) the folding of the main chains of the three proteins is essentially the same though there are significant differences on the molecular surface; 2) the spatial arrangements of the catalytic triads in the three proteins are similar to each other; 3) in SET and S. griseus trypsin a short stretch of 3(10)-helix is found through Ala56 to Thr59; His57 in this segment is one important amino acid residue involved in the active sites.

Amino Acid Sequence↗
PubMed1991

There is no correlation between function and lymphokine production of HBs-antigen-specific human CD4(+)-cloned T cells.

The question whether antigen-specific human CD4+ T cells can be classified on the basis of appropriate and fixed lymphokine production patterns and their corresponding functions still remains to be elucidated. We generated ten CD4+ T-cell clones specific for HBsAg from HBsAb-positive but HBsAg-negative individuals. Seven of these clones exhibited helper activity for HBsAb response, while the three other clones did not. Both helper- and non-helper-type T-cell clones produced interleukin 4 (IL-4) after antigenic stimulation. By stimulation with phytohaemagglutinin (PHA) plus phorbol myristate acetate (PMA), three of the seven helper-type clones produced interleukin 2 (IL-2) in addition to IL-4. However, the other four helper-type clones did not produce IL-2 by such stimulation, although they continued the production of IL-4. All non-helper-type T-cell clones produced a large amount of IL-2, and some of them completely became an IL-2 producer after certain stimulation. These results suggested that both helper- and non-helper-type CD4+ T-cell clones specific for HBsAg might have no strict pattern of lymphokine production as in the TH1/TH2 dichotomy of murine CD4+ T cells. The data also revealed that lymphokine-producing capacity of individual cloned T cells is changeable depending upon the sort of activation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

[Etiologic and pathophysiological characteristics of cirrhosis of the elderly].

To evaluate the etiologic and pathophysiological characteristics of the aged cirrhotics, a total of 219 cirrhotic patients who admitted to our department between 1975 and 1989 was divided into the three age groups; less than or equal to 49 (Group A, n = 70), 50-59 (Group B, n = 77) and greater than or equal to 60 (Group C, n = 72) years and compared. The frequency of female patients was significantly higher in Group B and C than Group A, respectively. The age-related variation in etiologies of cirrhosis was analyzed among patients between 1975 and 1989, as well as those observed in 1990, when the assay for antibody to hepatitis C virus (anti-HCV) was available. Compared with Group A, patients with Group C had a lower incidence in HBsAg positive and alcoholic cases. The incidence in cases of unknown cause increased with age and in the elderly over 70 anti-HCV negative cases were found in approximately 45 per cent, the incidence being significantly higher than that of the 50-to-59 year age group. Of the Group C patients 10.6 per cent had gastrointestinal bleeding, which was significantly lower in frequency as compared with 28.6 per cent of Group A. In contrast, the frequency of the other symptoms including jaundice, ascites and encephalopathy did not differ with age. Among various liver function indices the value of gamma-GTP was significantly lower and that of cholesterol was significantly higher in Group C than in Group A, although albumin tended to decline with age. When the extent of endoscopic findings of esophageal varices were compared between the elderly over 60 and the under 60s, the former included the less advanced cases than the latter. The hemodynamic studies revealed that the portal pressure and hepatic blood flow did not differ among the three age groups, but the cardiac index reduced and total systemic vascular resistance increased with age. Regarding the cause of death, the frequency of gastrointestinal bleeding was lower in Group B and C than in Group A. From these results it may be concluded that an approximately half of cirrhosis of the elderly occurs for no known cause other than HBV, HCV and alcohol, and that the frequency of gastrointestinal bleeding as well as the extent of esophageal varices appear to decline with age.

Adult↗
PubMed1991

Population of Salmonella serovar typhimurium in the cecum of gnotobiotic chickens with Escherichia coli and intestinal bacteria.

To test the interaction between various species of bacteria and Salmonella serovar typhimurium (S. typhimurium), the population of S. typhimurium was measured in the cecum of gnotobiotic chickens in the presence of Escherichia coli (E. coli) and one of the four intestinal bacteria; Lactobacillus acidophilus. Clostridium perfringens, Bifidobacterium thermophilum and Bacteroides vulgatus. Competitive exclusion of S. typhimurium by di-flora chicken was not demonstrated. But the population of S. typhimurium was temporarily suppressed in di-flora chickens with E. coli and L. acidophilus. In penta-flora chickens with E. coli and these four intestinal bacteria, the population of S. typhimurium was suppressed for only 2 days. In normalized chickens, the population of S. typhimurium was markedly suppressed.

Animals↗
PubMed1991

[Diffuse panbronchiolitis in two brothers with different clinical courses].

Diffuse panbronchiolitis in two brothers is reported. The elder brother aged 46, was admitted in May 1983 due to severe dyspnea and productive cough, which had gradually worsened over several years. He had severe hypoxemia and hypercapnia. He died at age 47 of respiratory failure due to pseudomonas infection despite antibiotic therapy. The younger brother, at age 41, was admitted in March 1983 due to fever, productive cough, and abnormal shadows on chest X-ray films. He showed mild hypoxemia and his symptoms improved with antibiotic treatment. Since then he has been followed as an outpatient for over 7 years while taking 400 mg of Erythromycin per day, and he has had no exacerbation. These two cases had different clinical courses despite the facts that both had similar conditions of chronic sinusitis and appeared to be exposed to no special environmental or occupational hazards. These facts suggest that not only intrinsic factors, such as defenselessness of airways, but extrinsic factors such as viral, mycoplasmal, or bacterial infection may act together on the mechanisms of the onset and progression of diffuse panbronchiolitis.

Adult↗
PubMed1991

Preparation of a drug-induced allergic hepatic disorder model with penicillin as hapten.

A drug-induced allergic hepatic disorder model was established using a hapten and carrier. Penicillin G was bound to glycine for the preparation of N-hydroxy succinic imidylglycinyl benzylpenicillate (PG-Gly-OSu). Using this as the hapten and liver protein as the carrier, guinea pigs were sensitized with liver protein bound to PG-Gly-OSu. After 2 weeks, the sensitized guinea pigs were directly challenged with hepatocytes bound to PG-Gly-OSu through a mesenteric vein and hepatocellular disorder was induced. When the sensitized guinea pigs were challenged with PG-Gly-OSu alone or with liver protein alone, hepatocellular disorder could not be induced. These results suggest that the combination of PG-Gly-OSu as the hapten and liver protein as the carrier elicits a hepatocellular disorder similar to drug-induced allergic hepatitis.

Animals↗
PubMed1991

Reduction in hepatic venous pressure gradient as a consequence of volume contraction due to chronic administration of spironolactone in patients with cirrhosis and no ascites.

The effect of plasma volume contraction induced by a 4-wk administration of spironolactone or furosemide on the hepatic venous pressure gradient was evaluated in consecutively allocated patients with cirrhosis and no ascites. In the spironolactone group (n = 15), the hepatic venous pressure gradient decreased significantly (p less than 0.005), by 21.8%, with a significant contraction of circulating plasma volume (p less than 0.01). Although there were no statistically significant correlations between the change in hepatic venous pressure gradient and changes in circulating plasma volume or in simultaneously determined systemic hemodynamics, a significant negative correlation (r = -0.74, p less than 0.01, n = 12) between the hepatic venous pressure gradient change and the post-treatment plasma aldosterone levels was found. However, in the furosemide group (n = 10), the hepatic venous pressure gradient and circulating plasma volume did not significantly decrease. Our data demonstrated a significant reduction in the hepatic venous pressure gradient on a chronic administration of spironolactone, which may have been due to volume contractions in patients with cirrhosis and no ascites.

Adult↗