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Biomedical subjects

T Okanoue

Publications and source records attributed to T Okanoue.

At least 109 records · Page 6Linked to original sources

[Side effects of interferon on endocrine and respiratory system in 545 cases of chronic hepatitis C].

We investigated the side effects of interferon (IFN) on the endocrine and respiratory system in 545 cases of chronic hepatitis C. Eleven of 494 (2.2%) patients with chronic hepatitis C who were treated with natural or recombinant interferon (IFN) developed thyroid disease while on treatment. Eight patients developed hyperthyroidism and 3 patients developed hypothyroidism. All 11 patients required definitive therapy, who became euthyroid after the therapy. Two patients received nIFN alpha and one patient received rIFN alpha 2b developed diabetes mellitus. Two patients received rIFN alpha 2a and rIFN alpha 2b, respectively, developed interstitial pneumonia 12 weeks and 24 weeks later, respectively. One patient showed positive reaction for RA test and LE factor and positive LE cell, and complained of fever, arthralgia and dry cough. These phenomenon disappeared after the cessation of IFN therapy.

Adult↗

[Autoimmune disorders in interferon therapy].

Interferons (IFNs) have immunomodulatory properties such as direct increase in the production of pathogen autoantibodies, enhanced cytotoxic T cell and B cell activities, inhibition of T suppressor cell function and induction of HLA class I antigen expression. These actions of IFN induce autoimmune disorders including autoimmune thyroiditis, hemolytic anemia and thrombocytopenia, SLE, rheumatoid arthritis and psoriasis, however, these autoimmune diseases except for autoimmune thyroiditis, are rare among side effects of IFN therapy. Most of the patients showing these autoimmune disorders during IFN treatment have predisposal immunological abnormalities such as positive ANA and antithyroidal autoantibodies. We described here autoimmune disorders during and after IFN treatment among 1023 cases with chronic active type C hepatitis. The cases with SLE, thrombocytopenic purpura, rheumatoid arthritis and psoriasis showed good prognosis after cessation of IFN administration.

Adult↗

[A case of Budd-Chiari syndrome treated by radical operation under hepatic perfusion and extracorporeal circulation].

A 41-year-old male patient of Budd-Chiari syndrome associated with membranous obstructions of the retrohepatic inferior vena cava and the left hepatic vein was reported. A radical operation was carried out. The retrohepatic inferior vena cava was reconstructed by a ringed EPTFE patch graft after endovenectomy with the aid of extracorporeal circulation for caval and portal bypasses utilizing cold hepatic perfusion. The patient has been doing well 18 months after the operation.

Adult↗

Experimental study of the reversibility of sinusoidal capillarization.

This study investigated the reversibility of sinusoidal capillarization in fibrotic rat liver induced by thioacetamide (TAA; 200 mg/kg body weight three times a week). Six weeks later, collagen fibers and hepatic lobular disarrangement were observed on light microscopy and basement membrane formation was noted in the space of Disse. Sinusoidal endothelial fenestrations (SEFs) were decreased in size and number (defenestration), and factor VIII-related antigen was observed in the cytoplasm. We also clarified the phenotypic reversibility of the sinusoidal endothelial cells. After 4 months following discontinuation of TAA exposure, the diameters and numbers of SEFs were increased. Six months later, the basement membrane in the space of Disse disappeared (as assessed by electron microscopy) and 12 months later, factor VIII-related antigen also disappeared. These results indicate that phenotypical changes in the sinusoidal endothelial cells and sinusoidal capillarization in hepatic fibrosis may be reversed.

Animals↗

Significance of pre-S region-defective hepatitis B virus that emerged during exacerbation of chronic type B hepatitis.

A defective form of the hepatitis B virus has been found in a patient with chronic type B hepatitis. Sequence analysis of the viral DNA after polymerase chain reaction amplification revealed a 117-base pair deletion (nucleotides 3129-53, subtype adr). This deletion includes the initiation codon of the pre-S2 region and a newly created in-frame stop codon in the pre-S1 region (nucleotide 3055) located 230 base pairs downstream from the pre-S1 initiation codon. This virus coexisted with the wild-type virus during the exacerbation period, as evidenced by an elevation of serum transaminase levels. It was not detected in the stable period, and the blood chemistry results were normal. We assayed antibodies against the mutation-related region by enzyme immunoassay in serial serum samples to clarify the mechanism of the emergence of this variant virus. Antibodies against the pre-S2 region were negative; however, the antibody response against the pre-S1 epitopes coincided with the appearance of the variant virus. These findings suggest that an activated T-cell and B-cell response had developed against the pre-S1 region during hepatic inflammation in this patient and that, consequently, selection occurred for a pre-S antigen-defective mutant strain of the virus that might be resistant to such an immune response.

Adult↗

Hemodynamic characterization in experimental liver cirrhosis induced by thioacetamide administration.

Systemic and splanchnic hemodynamics in experimental liver cirrhosis in rats induced by thioacetamide were evaluated by the radioactive microsphere method. Cardiac output and regional blood flow were measured in conscious and anesthetized control and cirrhotic rats. The conscious thioacetamide-treated rats had hyperdynamic circulation with an increased cardiac index (300 +/- 10 vs 258 +/- 3 ml/min/kg body weight, P < 0.001) and increased portal venous inflow compared with the controls (64.60 +/- 2.4 vs 48.39 +/- 0.88 ml/min/kg body weight, P < 0.001). Under pentobarbital anesthesia, the hyperdynamic circulation of the cirrhotic rats was maintained, with an increased cardiac index (276 +/- 7 vs 229 +/- 5 ml/min/kg body weight, P < 0.001) and increased protal venous inflow compared with the controls (72.47 +/- 3.0 vs 54.08 +/- 1.2 ml/min/kg body weight, P < 0.001). Portal pressure, portal venous resistance, and portal systemic shunting increased significantly while splanchnic arterial resistance decreased significantly in cirrhotic rats. Thioacetamide-induced cirrhosis is a useful model for the hemodynamic study of portal hypertension and remains useful in hemodynamic studies in the basal state under pentobarbital anesthesia.

Anesthesia, General↗

Effect of a somatostatin analogue (SMS 201-995) on hemodynamics and glucagon secretion in cirrhotic rats.

The effects of somatostatin analogue, SMS 201-995, on systemic and splanchnic hemodynamics and glucagon secretion were investigated in control and cirrhotic rats induced by thioacetamide administration. Hemodynamics were measured using the radioactive microsphere method. Immunoreactive glucagon (IRG) was determined in the portal vein and femoral artery and the splanchnic output (OP) of IRG was calculated. In control rats, SMS 201-995 induced a decrease of 5.6% in portal venous inflow and a 25.8% decrease in OP of IRG. In cirrhotic rats, SMS 201-995 produced a 14% decrease in portal pressure, a 13.6% decrease in portal venous inflow, and a 57.8% decrease in OP of IRG. In systemic hemodynamics no significant changes were noted following SMS 201-995 administration in the control or cirrhotic rats. The ratio of cirrhotic rats to the controls in the rate of decrease in portal venous inflow was similar to that in the percentage of decrease in OP of IRG. We conclude that SMS 201-995 is useful for the treatment of portal hypertension because of its effect of reducing portal pressure with mild changes in systemic hemodynamics. We suspect that the decrease in portal venous inflow by SMS 201-995 is mainly due to a reduction in the release of glucagon, a vasodilatory gastrointestinal hormone.

Animals↗

Effects of bile acids and taurine on the lipid fluidity of hepatic microsomes in normal and bile duct-ligated rats--a spin label study.

In cholestasis and obstructive jaundice, hepatic bile acids and taurine content increase significantly and bile acids change in compositions. For example, increases in cholic acid, beta-muricholic acid and taurine-conjugated bile acids occur in rats. In this study, to clarify the significance of changes in bile acid composition in obstructive jaundice, the effects of various bile acids and taurine on the fluidity of the hepatic microsomal membrane were studied by the electron spin resonance spin-label method in normal and bile duct-ligated (for 10 days) rats. The flow properties (order parameter) of the shallow and deep layers of the membrane were determined with 5- and 12-doxyl stearic acid, respectively. Bile acids mainly affected the fluidity of the shallow membrane layer. The fluidity of the hepatic microsomal membrane was decreased in bile duct-ligated rats. Conjugated cholic acid (taurine-conjugated cholic acid, glycine-conjugated cholic acid and non-conjugated beta-muricholic acid exerted effects that increased fluidity in comparison with non-conjugated cholic acid and chenodeoxycholic acid, a precursor of beta-muricholic acid. Taurine had no clear effect on fluidity. In conclusion, cholic acid conjugation and beta-muricholic acid formation may be mechanisms which protect against the decrease in lipid fluidity of hepatic biomembranes in cholestasis or obstructive jaundice. Taurine may also affect fluidity through the formation of taurine-conjugated bile acids.

Animals↗

Asymptomatic primary biliary cirrhosis in HTLV-I-associated myelopathy.

A 54-yr-old woman was admitted for complaints of slowly progressive gait and bladder disturbance, and HTLV-I-associated myelopathy (HAM/TSP) was diagnosed by positive antibodies to HTLV-I, both in her serum and cerebrospinal fluid. In the course of a diagnostic evaluation, she was found to have asymptomatic primary biliary cirrhosis. In immunohistochemistry, a fair number of her hepatocyte nuclei stained strongly positive for HTLV-I core protein, suggesting that HTLV-I may infect hepatocytes. The present case demonstrates that the spectrum of HTLV-I infection may be broad, and suggests the relationship between HTLV-I-associated myelopathy and primary biliary cirrhosis by autoimmune process.

Female↗

Defenestration of the sinusoidal endothelial cell in a rat model of cirrhosis.

We characterized the structural and immunohistological changes of sinusoidal endothelial cells that occur during cirrhosis in rats made cirrhotic with thioacetamide. Thioacetamide (200 mg/kg body wt) was injected intraperitoneally three times a week into male Wistar rats. Two, 4, 6 and 12 wk later, rat livers were observed under transmission and scanning electron microscopy and regular microscopy and immunostained with laminin and von Willebrand factor (factor VIII-related antigen) antibodies. The diameters and numbers of sinusoidal endothelial fenestrations did not change significantly after 2 wk in the thioacetamide-treated rats; however, they decreased within 4 wk after thioacetamide treatment. A basement membranelike structure in Disse's space was noted 6 wk after thioacetamide treatment. Laminin was detected in Disse's space after 4 wk. In vitro, in cultured sinusoidal endothelial cells, the diameter of sinusoidal endothelial fenestrations was significantly lower at 6 wk in thioacetamide-treated rats. von Willebrand factor was detected in the cytoplasm as granular fluorescence after 6 wk of thioacetamide treatment. These results suggest that as fibrosis develops in cirrhosis, the structural and immunohistochemical characteristics of sinusoidal endothelial cells change.

Animals↗

Functional heterogeneity of rat liver macrophages: interleukin-1 secretion and Ia antigen expression in contrast with phagocytic activity.

To clarify whether immunological heterogeneity exists among liver macrophages and whether this possible heterogeneity corresponds to varying degrees of phagocytic activity, we fractionated liver macrophages according to size via centrifugal elutriation and studied their ability to ingest latex beads, to express Ia antigen and to secrete interleukin-1 (IL-1) in vitro. Larger liver macrophages were found to be more active in ingesting latex beads than smaller ones (p less than 0.01), while smaller liver macrophages were more active in Ia antigen expression and evidenced greater fluorescence at cytofluorometric examination. In addition, smaller liver macrophages elaborated more IL-1 than the larger liver macrophages (p less than 0.05). These results indicate that liver macrophage heterogeneity is seen in at least two important macrophage functions: phagocytosis of large molecules, which provides an important scavenger function, and Ia antigen expression and IL-1 secretion, important components of the immune response.

Animals↗

Magnetic resonance imaging for the diagnosis of esophago-aneurysmal fistula.

A 77-year-old woman who complained of dysphagia was found to have an aneurysm in the descending aorta. Magnetic resonance imaging (MRI) demonstrated the state of thrombi, a thin and irregular soft tissue signal between the aneurysm and the esophagus, which suggested an esophago-aneurysmal fistula revealed by the operation. MRI was effective in the evaluation of the status of aneurysm.

Aged↗

Elevated interleukin-6 and gamma-globulin during interferon therapy of hepatitis B.

A 49-yr-old man with chronic hepatitis B manifested hypergammaglobulinemia, lymphadenopathy, and a high serum interleukin-6 level following treatment with recombinant human alpha-interferon. One month later, when the patient was treated with natural beta-interferon, serum levels of interleukin-6 and gamma-globulin increased again. The serum gamma-globulin decreased to the pretreatment level after discontinuation of interferon therapy. The serum alanine aminotransferase level remained normal for 6 months. In this case, hypergammaglobulinemia and lymphadenopathy, as well as the elevated serum interleukin-6 level, were considered to be signs of highly enhanced humoral immunity related to alpha- and beta-interferon therapy.

Alanine Transaminase↗

Primary gastric T-cell lymphoma with manifold histologic appearances.

A rare case of malignant T-cell lymphoma with manifold histologic appearances was described. The lymphoma occurred in the stomach of a 50-year-old Japanese male. Grossly, the lymphoma exhibited a deeply ulcerated mass. Histologically, in addition to diffuse infiltrate of large lymphoid cells with deeply indented nuclei, there were many epithelioid cell granulomas, remarkable tissue eosinophilia and stromal fibrosis, mimicking inflammatory disease. Immunohistochemical studies and a gene analysis demonstrated the T-cell phenotype.

Biomarkers, Tumor↗

Vitamin K concentrations in the plasma and liver of surgical patients.

Vitamin K deficiency has been reported in patients who were treated with antibiotics and placed on poor diets after surgery. High-performance liquid chromatography (HPLC) was used to study the influence of dietary intake on vitamin K concentrations in surgical patients (n = 22). Plasma phylloquinone decreased rapidly from 1.19 +/- 0.16 to 0.47 +/- 0.12 nmol/L (means +/- SEM, n = 11) on a low-phylloquinone diet and from 1.16 +/- 0.12 to 0.36 +/- 0.07 nmol/L (n = 11) by postoperative fasting. A small amount of phylloquinone and a large amount of menaquinone were found in liver tissue. Phylloquinone concentration was 28.0 +/- 4.3 pmol/g liver (wet weight) on the standard diet (n = 7) whereas it was 6.8 +/- 1.1 pmol/g on the low-phylloquinone diet after 3 d (n = 8). Because phylloquinone is rapidly depleted by fasting, it may be difficult to prevent vitamin K deficiency by dietary phylloquinone alone during long-term fasting after surgery.

Adult↗

Calcium-associated cytoprotective effect of taurine on the calcium and oxygen paradoxes in isolated rat hepatocytes.

Our study was designed to determine the calcium and oxygen paradoxes in isolated rat hepatocytes, and to evaluate the cytoprotective effects of taurine on hepatocytes during oxygenation, hypoxia, and on these paradoxes. The calcium and oxygen paradoxes were clearly revealed in isolated rat hepatocytes. As the formation of the superoxide radical was accelerated by the hyperbaric conditions and the calcium ions, drugs such as superoxide dismutase and a calcium channel blocking agent (verapamil), prevented these paradoxes. Taurine decreased the oxygenation-induced lipid peroxidation of hepatocytes, and prevented the hypoxia-induced hepatocyte death in a calcium-containing medium, but not in a calcium-free medium. Taurine also protected the hepatocytes from injuries associated with the calcium and oxygen paradoxes due to the inhibition of sudden calcium influx into the hepatocytes.

Animals↗