[Mechanisms for flow-induced responses of vascular endothelial cells].
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Biomedical subjects
Publications and source records attributed to K Fujiwara.
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OBJECTIVE: To assess the efficacy of interferon therapy for chronic hepatitis C among habitual drinkers. METHODS: Ninety-five hepatitis C virus ribonucleic acid-positive patients with chronic hepatitis were treated with four standardized regiments of interferon. Patients were divided into four groups based on the degree of daily alcohol consumption and duration of abstinence before treatment: 47 infrequent drinkers, 12 moderate drinkers who had consumed more than 23 gm but less than 69 gm of ethanol daily but stopped drinking for 39 +/- 18 months before therapy, 19 heavy drinkers I who had consumed more than 69 gm of ethanol daily but stopped drinking for 38 +/- 37 months before treatment, and 17 heavy drinkers II who consumed more than 69 gm ethanol daily soon before treatment. RESULTS: The rate of responders; in whom serum ALT levels remained normal for 6 months after the end of treatment, was in a decreasing order of: infrequent drinkers (36.2%), moderate drinkers (33.3%), heavy drinkers I (26.3%), and heavy drinkers II (5.9%) (p < 0.05, infrequent drinkers vs heavy drinkers II). The negative rate of serum hepatitis C virus ribonucleic acid 6 months after the end of treatment was in a similar order (27.7%, 25.0%, 15.8%, and 0%, respectively) (p < 0.05, infrequent drinkers vs heavy drinkers II). CONCLUSION: Heavy drinking will reduce the efficacy of interferon therapy for chronic hepatitis C, and the adverse effect of drinking on efficacy might be reversed, partly, by abstinence for a long period before treatment.
A 23-year-old man was admitted to our hospital complaining of swelling and pain in the penis. Examination revealed fracture of the penis. The tear in the tunica albuginea was not palpable on physical examination of the penis, but magnetic resonance imaging (MRI) revealed the exact site of the tear in the tunica albuginea. MRI was very useful in localizing the site of fracture.
Pulmonary artery banding (PAB) is essential for infants of complicated cardiac anomaly without pulmonary stenosis, especially those who require future Fontan type correction. In order to avoid pulmonary artery branch stenosis or uneven growth we utilize expanded polytetrafluoroethylene (E-PTFE) suture (Gore-Tex suture, CV-0) as a banding material. We performed three PABs (two newborns and one infant) with this suture. All children were doing well after the banding and no one revealed residual pulmonary hypertension or pulmonary artery distortion in the postoperative catheter study. One patient successfully underwent total cavopulmonary connection eight months after PAB. We believe E-PTFE suture is an advantageous material of PAB for newborns and young infants.
From January 1980, through December 1995, 60 patients underwent surgical treatment of infective endocarditis (IE) at Sakakibara Hospital. Of 60 patients, 40 showed active endocarditis and 20 healed endocarditis at the time of operation. The over-all hospital mortality was 10% (6/60). The complication of cerebral accident (embolism and bleeding) was related to a higher incidence of operative mortality. The reconstructions of destruction and disruption of ventricular-aortic or mitral-aortic continity in the presence of acute infection of the annular tissue were in need of radical and complex surgical techniques. It is recommended to follow up these patients thoughtfully and to perform reoperation or re-reoperation before a patient develops severe heart failure or multiple organ failure.
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OBJECTIVE: To compare the efficacy of ultrasound-guided percutaneous acetic acid injection and segmental transcatheter arterial embolization for hypervascular small hepatocellular carcinoma. METHODS: The prognosis of 40 patients with one to three angiographically hypervascular hepatocellular carcinoma smaller than 3 cm in diameter treated with either percutaneous acetic acid injection (25 patients) or transcatheter arterial embolization (15 patients) during the past 4.5 yr were analyzed retrospectively. RESULTS: After initial therapy, none of 25 patients treated with percutaneous acetic acid injection developed ascites, whereas 5 of 15 (33%) patients treated with transcatheter arterial embolization developed it (p < 0.01). All tumors became smaller once after each therapy. However, local recurrence (reenlargement of the original tumor) occurred in 1 of 29 (3%) tumors treated with percutaneous acetic acid injection and 11 of 22 (50%) tumors treated with transcatheter arterial embolization (p < 0.005). During the follow-up, 4 of 25 (16%) patients treated with percutaneous acetic acid injection and 10 of 15 (67%) patients treated with transcatheter arterial embolization died. The 1-, 2-, and 3-yr survival rate was 100, 94, and 83%, respectively, in patients treated with percutaneous acetic acid injection and 72, 65, and 39% in patients treated with transcatheter arterial embolization (p < 0.005). The cancer-free survival rate was also significantly better in the former than in the latter group (p < 0.005). CONCLUSIONS: Percutaneous acetic acid injection is superior to segmental transcatheter arterial embolization in the treatment of hypervascular small hepatocellular carcinoma.
The effect of alcohol intake on the efficacy of interferon (IFN) therapy was evaluated retrospectively in patients with chronic hepatitis C diagnosed by liver histology and positive serum hepatitis C virus (HCV)-RNA. Patients included 119 given IFN therapy and 11 no IFN therapy. Serum HCV-RNA was measured 6 months after discontinuation of IFN therapy in 92 treated patients, 27.2% of whom showed disappearance of serum HCV-RNA. Multivariate logistic regression analysis revealed that this disappearance was affected by alcohol intake, the presence of its history (p < 0.05) or cumulative alcohol consumption (kg) (p < 0.01), and serum HCV-RNA levels (p < 0.001). The odds ratio associated with serum HCV-RNA still positive at 6 months was 7.018 (95% confidence interval: 1.444-34.062) and 1.004 (1.001-1.007) for the presence of alcohol intake history and the cumulative alcohol consumption, respectively. Other predictor variables-such as sex and age of patients, history of blood transfusion, HCV genotype, histological findings of the liver, and types of IFN-had no influence on the efficacy of the therapy. Cumulative alcohol consumption showed a negative correlation with serum HCV-RNA levels pretreatment, when the outcome variable was divided into two categories based on serum HCV-RNA levels: 10(6) copy/ml or less and 10(7) copy/ml or more. Alcohol intake was positively correlated with histological extent of alcoholic fibrosis, but affected neither grading nor staging of chronic viral hepatitis. We conclude that alcohol intake was a risk factor on the efficacy of IFN therapy in chronic hepatitis C patients. This effect was independent of serum HCV-RNA levels and histological findings specific for viral hepatitis in the liver.
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In the course of myosin-catalyzed ATP hydrolysis, certain amino acid residues in myosin interact with counterparts in actin to produce the relational changes that underlie muscle contraction; some of these interactions are ionic, but the stronger interactions are hydrophobic. In an effort to identify myosin residues participating in hydrophobic interactions, myosin (from smooth muscle) fragments with mutations at suspected sites were engineered and compared with wild-type fragments. It was found that the ATPase of doubly mutated (Trp546Ser and Phe547His) fragments was minimally activated by actin and did not decorate actin well to form the regular arrowhead pattern characteristic of myosin binding to actin filaments. Thus, we suggest that Trp546 and Phe547 are important participants in the hydrophobic actin-myosin interaction.
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The regulatory mechanisms of microcirculation might differ in the liver from other organs, because macrophages are resident in the hepatic sinusoids and sinusoidal endothelial cells are unique in shape and function. Thrombomodulin expression in endothelial cells and tissue factor activity in isolated macrophages were studied in the liver and lung of rats. In normal rats, the thrombomodulin expression was minimal in hepatic sinusoids, but prominent in pulmonary capillaries, while the tissue factor activity in the presence of endotoxin was higher in pulmonary macrophages than in Kupffer cells, although the levels in the absence of endotoxin were comparable in both cells. The tissue factor activity in hepatic macrophages was increased after priming of the cells with Corynebacterium parvum or after induction of liver necrosis or cirrhosis with carbon tetrachloride. In the necrotic or cirrhotic liver, increased thrombomodulin expression was seen along capillaries extending in necrotic areas and regenerating nodules, but this increase was minimal in the Corynebacterium parvum-treated rat liver. Blood coagulation equilibrium in microcirculation regulated by endothelial cells and macrophages may differ between the liver and lung. Such equilibrium in the liver may vary depending on pathological status.
The transport of cystine has been investigated in mouse peritoneal macrophages incubated with oxidized low-density lipoprotein (oxi-LDL; low-density lipoprotein, LDL). The transport activity for cystine was potently induced by oxi-LDL but not by native or acetylated LDL. The response of the cells to oxi-LDL was dependent on the extent of oxidative modification of LDL. The transport activity for other amino acids was not induced by oxi-LDL. GSH content increased in macrophages incubated with oxi-LDL and this increase was accounted for by the induction of the cystine transport activity because the increase was completely blocked by glutamate or homocysteate which shared the transport system for cystine and thus inhibited the uptake of cystine competitively.
ICAM-1 was not detected immunohistologically in hepatocytes in normal rats, but detectable in centrilobular degenerative hepatocytes in carbon tetrachloride-intoxicated rats. ICAM-1 expression was observed even in normal hepatocytes following liver perfusion with Hank's balanced salt solution at a flow rate of 4.2 mL/g liver weight/min or with the same solution containing collagenase or EGTA at the physiological flow rate (1.4 mL/g liver weight/min). Such expression was also observed when liver perfusion was performed after pretreatment of rats with cycloheximide. On electron microscopy, ICAM-1 was exclusively stained on hepatocyte plasma membrane that was detached from the plasma membrane of adjacent hepatocytes. ICAM-1 mRNA and ICAM-1 protein were detected in hepatocytes freshly isolated from normal rats. Thus, ICAM-1 expression in degenerative hepatocytes as well as in hepatocytes following liver perfusion can be assumed to result from dissociation of cell-to-cell contact.
To investigate the flow sensing and the early signaling events in vascular endothelial cells (ECs), we surveyed changes in phosphotyrosine levels of glycoproteins using immunoblot analyses. Cultured bovine arterial ECs were exposed to steady laminar flow by using a coneplate type flow apparatus and glycoprotein fractions were partially purified by lectin affinity column chromatography. A 128 kDa protein band in the Ricinus-communis-agglutinin-bound fraction showed a rapid and consistent augmentation of tyrosine phosphorylation by flow. Cell surface domain-restricted biotinylation revealed that the 128 kDa glycoprotein has extracellular domain(s). Tyrosine phosphorylation of the 128 kDa protein was also observed in ECs subjected to hyper- or hypo-osmotic shock but not in ECs stimulated by Ca2+ mobilizing agents.
The transport of cystine has been investigated in mouse peritoneal macrophages cultured in vitro. The transport activity for cystine was very low in freshly isolated macrophages but was potently induced during culture in the presence of bacterial lipopolysaccharide (LPS) at concentrations as low as 0.1 ng/ml. The transport activity for cystine was enhanced when the cells were incubated with tumour necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma) or interleukin-1. IFN-gamma was rather repressive in the induction of the activity by LPS or TNF-alpha. The transport activity for cystine induced by LPS has been characterized. Cystine was transported mainly by Na(+)-independent system and the uptake of cystine was inhibited by extracellular glutamate and homocysteate, but not by aspartate, indicating that the transport of cystine in macrophages treated with LPS is mediated by System xc-. Glutathione content of the macrophages increased when they were exposed to LPS, and this increase was, at least in part, attributable to the induced activity of the cystine transport.
STUDY DESIGN: This study analyzed the natural course of cervical spine involvement in rheumatoid arthritis by serial radiographs. OBJECTIVES: The purpose was to determine the pattern of progression of cervical spine lesions in rheumatoid arthritis and predictors for the extent of progression. SUMMARY OF BACKGROUND DATA: Subluxation frequently occurs as a result of rheumatoid involvement of the cervical spine. It may be severe in patients with mutilans deformities in the hands and feet. The extent of progression in a given patient is still unpredictable. METHODS: Serial cervical radiographs in 49 patients with rheumatoid arthritis were analyzed. The extent of progression was evaluated by rheumatoid arthritis subset defined previously, which reflected the final extent of joint erosion in this systemic disease and could be roughly classified during early stages of the disease. RESULTS: In the upper cervical spine, reducible anterior atlantoaxial subluxation occurred first. Vertical subluxation of the axis appeared next. Irreducible change of preceding anterior atlantoaxial subluxation was a sign of the start of vertical subluxation. In subaxial lesion, subluxation occurred less frequently (22.4%) than upper cervical lesion (77.6%). The extent of progression was different with the rheumatoid arthritis subset. In the upper cervical spine, none of the subset with least erosive disease developed vertical subluxation, whereas 52% of the subset with more erosive disease and 88% of the subset with mutilating disease advanced to vertical subluxation. The extent of progression was well correlated with the number of joints with erosion. Subaxial subluxation was often seen and became irreducible in mutilating disease and more erosive disease, but not in least erosive disease. CONCLUSIONS: A progressive pattern of the upper cervical subluxations was clarified. That is, upper cervical lesions progressed from reducible anterior atlantoaxial subluxation to irreducible anterior atlantoaxial subluxation with vertical subluxation. This extent of progression was different with the rheumatoid arthritis subset, which was also related to the development of subaxial subluxation. The most aggressive arthritis classification, a subset with mutilating disease, had the more severe subluxation in both upper and subaxial cervical spine.