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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 235 records · Page 13Linked to original sources

Operation for nondissecting aneurysm in the descending thoracic aorta.

BACKGROUND: Little is known about the risks of mortality and morbidity after descending thoracic aortic aneurysm repair using left heart bypass and temporary arterioarterial bypass. METHODS: A multicenter, retrospective study was performed on 120 patients who were admitted to one of nine cardiovascular centers between January 1988 and December 1993 and underwent operation for nondissecting thoracic aortic aneurysm. The present series included 10 patients with ruptured aneurysm. Graft replacement was performed in 95 patients, patch repair in 22, and suture of the ruptured aorta in 3. Venoarterial bypass was used in 45 patients, left heart bypass in 56, and temporary arterioarterial bypass in 19 as circulatory support. The mean postoperative follow-up period was 30 +/- 21 months. RESULTS: Hospital mortality occurred in 7 patients (5.8%). Univariate analysis revealed that only aneurysmal rupture was related to hospital mortality. Brain or cord injury was observed in 4. Of nine deaths that occurred after discharge, five were related to aneurysm and two were due to vascular event. No significant difference was noticed in probability of survival according to the circulatory supporting method. Only aneurysmal rupture affected probability of survival. Multivariate analysis revealed that aneurysmal rupture was the only independent predictor for vascular death including hospital mortality. CONCLUSIONS: The present study confirms that aneurysmal rupture is a significant predictor for mortality and morbidity in aortic operations for nondissecting descending thoracic aneurysm, and that a similarly good outcome would be expected when using left heart bypass, temporary arterioarterial bypass, or venoarterial bypass.

Aged↗

Quasispecies nature of hepatitis C virus and response to alpha interferon: significance as a predictor of direct response to interferon.

BACKGROUND/AIMS: We evaluated the significance of the quasispecies nature of HCV as a predictor of the response to alpha interferon therapy in patients with chronic hepatitis C. METHODS: Natural alpha interferon was administered in 62 patients for 24 weeks (daily for 2 weeks, then three times weekly for 22 weeks) and factors were analyzed that could affect the response. HCV subtype, HCV RNA concentrations and the number of HCV quasispecies were evaluated before treatment. HCV RNA concentrations were measured by branched DNA probe assay. The number of HCV quasispecies was measured by fluorescence single-strand conformation polymorphism analysis. RESULTS: The HCV RNA concentration (p < 0.0001), HCV subtype (p = 0.0076), and the number of HCV quasispecies (p = 0.0024) were significantly associated with a complete response. Multivariate analyses showed that the number of HCV quasispecies was an independent predictor of the disappearance of HCV RNA during the administration of alpha interferon, but did not predict a relapse after its completion. Pretreatment concentration of HCV RNA was the only factor that was related to a long-term disappearance of HCV RNA. CONCLUSIONS: The number of HCV quasispecies was significantly related to the response to alpha interferon early in its administration. The pretreatment concentration of HCV RNA was mainly related to a relapse following completion of treatment.

Adult↗

Changes in blood supply in small hepatocellular carcinoma: correlation of angiographic images and immunohistochemical findings.

BACKGROUND/AIMS: To assess the changes occurring in blood flow with growth in small hepatocellular carcinomas, we analyzed the angiographic features and immunohistochemical findings in 35 hepatocellular carcinomas less than 2 cm in diameter. METHODS: Hepatocellular carcinomas were evaluated by digital subtraction angiography (DSA), ultrasound angiography with intraarterial CO2 microbubbles (USAG), and computed tomography during arterial portography (CTAP). Immunohistochemically, hepatocellular carcinomas were evaluated using QB-end/10 (QB) monoclonal antibody. RESULTS: All 18 moderately-differentiated hepatocellular carcinomas stained positively with QB antibody. No hepatocellular carcinomas without attenuation on CTAP were positive by immunohistochemistry, and two hepatocellular carcinomas with attenuation on CTAP also lacked staining. We observed four hepatocellular carcinomas without hypervascularity on DSA or USAG, which stained positively with QB antibody; these hepatocellular carcinomas had fatty metamorphosis. CONCLUSIONS: 1. Immunohistochemical findings are closely associated with angiographic findings regarding changes in blood supply. 2. All moderately-differentiated hepatocellular carcinomas have characteristics of hypervascularity, both by angiographic images and by immunohistochemistry. 3. The increase in arterial blood supply occurs later than the decrease in portal perfusion, which may indicate that the decrease in portal perfusion may not be the direct result of replacement by angiogenesis. 4. Some hepatocellular carcinomas with fatty metamorphosis, which are often hypovascular by angiographic evaluation, have hypervascular immunohistochemical characteristics.

Aged↗

Significance of tumor vascularity as a predictor of long-term prognosis in patients with small hepatocellular carcinoma treated by percutaneous ethanol injection therapy.

BACKGROUND/AIMS: We estimated the significance of the vascularity of small hepatocellular carcinoma (HCC) as a predictor of long-term prognosis in patients treated with percutaneous ethanol injection therapy (PEIT/PEI). METHODS: Fifty-four patients who have been followed-up in our hospital and who had HCC less than 20 mm in diameter were observed for 199 to 2074 days. Hepatic angiography (digital subtraction angiography; DSA and ultrasound angiography with intraarterial CO2 microbubbles; USAG) was performed before treatment in all cases, and the vascularity of the tumor was clinically evaluated. The survival rate was analyzed according to this vascularity. RESULTS: Of the 54 tumors, 24 had tumor stain on DSA, while 30 did not, and 38 showed enhancement on USAG, while 16 did not. The 3- and 5-year survival rates were 48.7 and 34.1% and 89.7 and 69.7% of patients with negative staining HCC (p = 0.0723). The rates were 48.6 and 36.7%, respectively, of patients with positive enhancement HCC on USAG, and both rates were 85.7% of patients with negative enhancement HCC (p = 0.0231). CONCLUSIONS: Tumor vascularity will play a role in the long-term prognosis of these patients with small HCC when they are treated with PEIT/PEI.

Administration, Cutaneous↗

Enhancement of potassium-, and angiotensin II-stimulated aldosterone production by the calcium chelator EGTA in bovine adrenal glomerulosa cells in vitro.

The present study was designed to assess the effect of the calcium chelator EGTA (ethylenglycolbis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid; 1.0 mM) on potassium (8 mM)- and angiotensin II (AII; 10 nM)-stimulated aldosterone production in bovine adrenal glomerulosa cells in vitro. The combined administration of EGTA and potassium, or of EGTA and AII, yielded a significant increase in the levels of aldosterone production. The net increment in aldosterone production after the combined administration of EGTA and potassium, or that after the combined administration of EGTA and AII was also significantly higher than the sum of that evoked by EGTA and potassium alone, or the sum of that evoked by EGTA and AII alone, respectively. At similar concentrations of extracellular ionized calcium ([Ca2+]out) or magnesium, the levels of agonist-stimulated aldosterone production were markedly elevated by the administration of EGTA. These results indicate that lowering [Ca2+]out concentrations with EGTA enhances potassium- and AII-stimulated aldosterone production in bovine adrenal glomerulosa cells in vitro. This enhancement may be predominantly due to another effect of EGTA, in addition to the stimulation of calcium entry into the cells.

Aldosterone↗

Steroids decrease uptake of carboplatin in rat gliomas--uptake improved by intracarotid infusion of bradykinin analog, RMP-7.

A blood-tumor barrier (BTB) limits delivery of antitumor agents to brain tumors. This study sought to determine whether dexamethasone (DXN) treatment of rats with intracranial gliomas would 1) further impair delivery of carboplatin to brain tumors, and 2) whether intracarotid infusion of the bradykinin analog, RMP-7, would improve delivery during concurrent DXN treatment. Wistar rats with RG2 gliomas were utilized and a unidirectional transport, Ki, of radiolabeled [14C] carboplatin was determined using quantitative autoradiography. In DXN pretreatment animals, 3 mg/kg/day of DXN was administered intraperitoneally for 3 days prior to Ki determinations. At 10 days after tumor implantation, Ki of [14C] carboplatin into DXN-treated tumors and brain surrounding tumor (BST) was significantly lower compared to non-DXN treated tumors and BST (3.30 +/- 0.91 vs. 4.47 +/- 1.80, p < 0.05, and 0.94 +/- 0.84 vs. 2.18 +/- 0.79, p < 0.05, respectively). Intracarotid infusion of RMP-7 (0.1 mg/kg/min) significantly increased the Ki for carboplatin in DXN-treated tumors (6.35 +/- 3.10 vs. 3.30 +/- 0.91, p < 0.01), however, RMP-7 increased Ki to a greater extent in tumors not pretreated with DXN (12.07 +/- 3.60 vs. 4.47 +/- 1.80, p < 0.0001). Our studies show that dexamethasone decreases transport of carboplatin into brain tumors. Intracarotid infusion of RMP-7 selectively increases carboplatin transport to tumors.

Animals↗

Stereoselective 4'-hydroxylation of phenytoin: relationship to (S)-mephenytoin polymorphism in Japanese.

AIMS: The aim of this study was to clarify whether phenytoin (PHT) stereoselective hydroxylation cosegregates with (S)-mephenytoin phenotype. METHODS: A single dose of PHT (100 mg) was administered orally to six healthy Japanese subjects in whom the genotype and phenotype of CYP2C19 had been determined previously. The urinary excretion profiles of the metabolites of PHT, (R)- and (S)-p-HPPH [5-(4-hydroxyphenyl)-5-phenylhydantoin] up to 361 postdose were compared between the two groups of poor metabolizers (PMs, n = 3) and extensive metabolizers (EMs, n = 3) with respect to CYP2C19. CYP2C9 genotype was also determined. RESULTS: All the alleles were found to be wild type (Arg144 Tyr358Ile359Gly417) in each subject. The mean value for cumulative urinary excretion of unchanged PHT was not significantly different between the PMs and the EMs. However, recovery of (R)-p-HPPH at 36 h was 3.5-fold lower and that of (S)-p-HPPH 1.3-fold lower in PMs than in EMs. Although the mean urinary excretion values for both metabolites were significantly lower in the PMs than in the EMs, the difference between the two groups was larger for (R)-p-HPPH. A significant negative correlation was observed between the hydroxylation index of omeprazole (the ratio between the serum concentrations of omeprazole and hydroxyomeprazole in blood samples drawn 3 h after drug intake) and the log10 0-12 h urinary recovery of (R)-p-HPPH. CONCLUSIONS: In humans, the 4'-hydroxylation of PHT is highly stereoselective towards formation of the (S)-enantiomer. Thus, (S)-hydroxylation by CYP2C9 might be the major determinant of the disposition of PHT. However, these results support the hypothesis that the stereoselective hydroxylation pathway of PHT to form (R)-p-HPPH cosegregates with the CYP2C19 metabolic polymorphism.

Administration, Oral↗

Hepatitis GB virus C genome in the serum of aplastic anaemia patients receiving frequent blood transfusions.

GB virus C (GBV-C) RNA was detected in five of 18 patients with aplastic anaemia who had received blood transfusions, whereas it was not detected in eight patients who had not received any transfusions. Antibody against hepatitis C virus (anti-HCV) was detected in nine patients in the transfusion group, compared with one of eight who had not received any transfusions. Therefore, the route of transmission of both GBV-C and HCV in these patients appeared to have been multiple blood transfusion. Since all of the GBV-C RNA-positive patients harboured anti-HCV, GBV-C seems to frequently superinfect with HCV. Neither GBV-C nor HCV is likely to have been a causative agent of the anaemia in the cases examined.

Adolescent↗

Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma.

To assess intrahepatic metastasis (IM) and multicentric occurrence (MO) after initial treatment of small hepatocellular carcinomas (HCC) < or = 2 cm in diameter, we performed clinical and pathological studies in 112 patients who underwent percutaneous ethanol injection therapy (PEIT) or hepatic resection for HCC from January 1985 to December 1994. Patients with intrahepatic recurrences were classified into two groups based on the type of recurrence: the IM group (n = 29, 50.9%) and the MO group (n = 28, 49.1%). Overall recurrence rates after initial treatment were 23.7% at 1 year, 64.5% at 3 years, and 76.1% at 5 years. In patients with IM, the majority of intrahepatic recurrences were observed within 3 years of initial treatment and the primary HCC lesions were closely related to the degree of tumor cell differentiation. Alternatively, intrahepatic recurrences occurred throughout the follow-up period in patients with MO, and the evidence of underlying liver disease (anti-HCV [antibody to hepatitis C virus] positive) and elevated serum alfa-fetoprotein (AFP) concentrations were closely associated with intrahepatic recurrence. Prognoses following additional treatment in MO group patients were superior to those in IM group patients. These results suggest that differentiation between IM and MO in patients with HCC is important for understanding the development and biological behavior of the tumor. That is, the early detection of intrahepatic recurrence and the institution of appropriate additional therapy (PEIT or hepatic resection) may prolong survival in patients with MO.

Adult↗

Enhanced cytokines delivery and intercellular adhesion molecule 1 (ICAM-1) expression in glioma by intracarotid infusion of bradykinin analog, RMP-7.

The effect of intracarotid infusion of the bradykinin analog, RMP-7, on blood-to-tumor and blood-to-brain transport of three cytokines were investigated. Wistar rats with RG2 gliomas were utilized and a unidirectional transfer constant, Ki, was determined using quantitative autoradiography. Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) were labeled with 125Iodine for quantitative transport studies using autoradiography. Radiolabeled cytokines were injected as an intravenous bolus. Intracarotid infusion of RMP-7 (0.1 microgram kg-1 min-1) increased the selective transport to tumors of IFN-gamma by 3.97-fold (p < 0.005), of TNF-alpha by 5.30-fold (p < 0.005), and of IL-2 by 4.34-fold (p < 0.005), compared to intracarotid saline infusion. To determine whether the increased IFN-gamma or TNF-alpha transport to tumors with RMP-7 could enhance expression of intercellular adhesion molecule 1 (ICAM-1) in tumors, ICAM-1 expression in RG2 glioma was evaluated by immunohistochemistry. Both IFN-gamma and TNF-alpha increased ICAM-1 expression of RG2 cells in vitro. In vivo, intracarotid infusion of IFN-gamma combined with RMP-7 significantly enhanced ICAM-1 expression in intracerebral RG2 gliomas compared to infusion of IFN-gamma without RMP-7. Expression of ICAM-1 was not enhanced by TNF-alpha combined with RMP-7. Intracarotid infusion of RMP-7 is a novel method of cytokines delivery to brain tumors.

Animals↗

Shift work and risk factors for coronary heart disease in Japanese blue-collar workers: serum lipids and anthropometric characteristics.

This study was conducted to determine if there is an association between shift work and risk factors for coronary heart disease (CHD) in Japanese male blue-collar shift workers. Health check-up data on serum lipid concentration and anthropometric indices of 33 three-shift workers and 27 two-shift workers were compared with those of day workers. The average years in age of the shift workers and day workers were 34.5 (SD = 7.1) and 32.7 (SD = 7.6), respectively. Serum total cholesterol levels of three-shift, two-shift and day workers were 5.70 (SD = 1.19) mmol/l, 4.81 (SD = 1.01) mmol/l, 4.98 (SD = 0.95) mmol/l, respectively, and the cholesterol levels of three-shift workers were significantly higher than the other workers (p < 0.05). In addition, the abdominal to hip circumference ratios were 0.905 (SD = 0.060) for three-shift workers and 0.877 (SD = 0.054) for day workers, with a significant difference (p < 0.05). In the present Japanese population, three-shift workers had higher risks of CHD than day workers, which was characterized by higher levels of serum total cholesterol and tendency to central obesity. These findings held when lifestyle factors were taken into account.

Adult↗

Immortalized gastric epithelial cell line GSM06 synthesizes hyaluronan under the influence of simian virus 40 large T-antigen expression.

GSM06 is a cell line established from the stomach of transgenic mouse harboring a temperature-sensitive simian virus 40 (SV40) large T-antigen gene. 3H-labeled macromolecules produced by the cells incubated with [3H] glucosamine were characterized to examine whether or not GSM06 cells synthesize mucin (mucus glycoprotein). The GSM06 cells grew until a confluent monolayer formed at 33 degrees C (the permissive temperature for SV40 large T-antigen expression), and the 3H-labeled macromolecules appeared in both cell extract and medium during culture for at least 1 week. Unexpectedly, almost all 3H-labeled macromolecules, which were excluded from a column of Sepharose CL-4B, were identified as hyaluronan by analyses using Sepharose CL-2B chromatography, cesium trifluoroacetate equilibrium centrifugation, treatment with dithiothreitol, and trypsin, hyaluronidase, and chondroitinase ABC digestion. At a nonpermissive temperature (39 degrees C), GSM06 cells grew only slightly, but produced much more hyaluronan than at 33 degrees C. The results indicate that GSM06 cells produce not mucin, but hyaluronan, and that the expression of large T-antigen may influence hyaluronan synthesis in GSM06 cells.

Animals↗

Myofibrillar myopathy. III. Abnormal expression of cyclin-dependent kinases and nuclear proteins.

The pathological process in myofibrillar myopathy (MFM) (previously also referred to as "desmin storage" or "intermediate filament myopathy") results in dissolution of myofibrils, accumulation of products of the degradative process, and abnormal ectopic expression of desmin, dystrophin, gelsolin, NCAM, and N-terminal components of beta-amyloid precursor protein. We now demonstrate that the abnormal fiber regions in MFM immunoreact strongly for (a) CDC2 kinase, the mitotic kinase that phosphorylates and disassembles intermediate filaments; (b) cyclin-dependent kinases CDK2, CDK4, and CDK7, which are involved in regulation of the cell cycle; (c) lamin B, which normally supports the inner nuclear membrane; and (d) the nuclear matrix associated protein. The normal muscle fiber lies in a terminally differentiated state and is refractory to reentry into the cell cycle. The abnormal expression of multiple cyclin-dependent kinases in the terminally differentiated muscle fiber implies inappropriate activation of positive regulators of mitosis and may signal a mitotic catastrophe. The dissolution of myofibrils may be due to hyperphosphorylation occurring during this event.

Adult↗

Radial nerve palsy associated with slightly angulated pediatric supracondylar humerus fracture.

This report reviews a case of radial nerve palsy associated with a supracondylar fracture of the right humerus. The patient was a four-year-old boy. Radiographs of the injury showed simple extension and a slightly angulated fracture. Complete radial nerve palsy was observed at the first consultation. After three months of conservative treatment without any obvious improvement, an operative exploration of the right radial nerve was conducted. Intraoperatively, the nerve was found to be transected, with both ends of the ruptured nerve buried in scar tissue at the fracture site. Five months after the nerve suture operation, the palsy was cured completely. This case shows that even a minimal displacement fracture can be associated with severe nerve injury that requires surgical treatment.

Child, Preschool↗

Role of endogenous cholecystokinin and cholecystokinin-A receptors in the development of acute pancreatitis in rats.

Recent studies provide significant evidence that cholecystokinin (CCK) is involved in the induction and development of acute pancreatitis in experimental animals. However, the results obtained with specific CCK-A (peripheral) receptor antagonists are still controversial. The present studies were undertaken to evaluate the involvement of endogenous CCK and the CCK-A receptors in the development of severe acute pancreatitis induced in Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have a selective defect in the CCK-A receptor. Three models of severe acute pancreatitis were induced by retrograde intraductal infusion of 4% sodium taurocholate, by the closed duodenal loop, or by a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine in OLETF rats and control Long-Evans Tokushima Otsuka (LETO) rats. Plasma CCK levels rose up to 4- to 14-fold over the preloading values after the onset of acute pancreatitis in all three models in both groups of rats. However, histologic alterations as well as the magnitudes of increase in serum amylase and lipase activity and the pancreatic wet weight were significantly less in the OLETF rats than those in the LETO rats. In addition, 72 h after the onset of arginine pancreatitis, massive destruction of pancreatic parenchyma with a significant reduction in serum amylase and lipase activities and pancreatic wet weight was observed in the LETO rats, whereas these changes were not seen in OLETF rats. These results suggest that endogenous CCK and CCK-A receptors play a role in the development of severe acute pancreatitis in rats.

Acute Disease↗

Significance of early measurement of serum hepatitis C virus RNA in predicting response to interferon therapy in patients with chronic hepatitis C.

BACKGROUND: Interferon can induce complete clearance of hepatitis C virus (HCV) in some patients with chronic hepatitis C. However, various side effects often require cessation of administration during the treatment period. Early prediction of response to interferon would be helpful. We evaluated measurement of serum HCV RNA 2 weeks after starting interferon as a predictor of response. METHODS: The presence of HCV RNA was measured in serum 2 weeks after starting therapy in 85 patients receiving natural interferon a (total 480 MU). RESULTS: Twenty-seven of 38 patients (71.1%) in whom serum HCV RNA had disappeared at 2 weeks achieved a sustained response. Only two out of 47 patients (4.3%) in whom serum HCV RNA had not disappeared at 2 weeks achieved a sustained response. Of 42 patients with pre-treatment HCV RNA concentrations less than 1 x 10(6) eq/ml, 26 of 30 patients (86.7%) whose HCV RNA had disappeared at 2 weeks achieved a sustained response, while only one of 12 patients (8.3%) whose HCV RNA was still detectable at 2 weeks had a sustained response. CONCLUSION: Clearance of serum HCV RNA after 2 weeks of treatment with interferon was more likely in patients with lower pre-treatment HCV RNA concentrations and they had a high likelihood of achieving a sustained response. In patients in whom serum HCV RNA was still detectable after 2 weeks of interferon therapy, a sustained response was most unlikely.

Adult↗

Streptococcal mitogenic exotoxin Z, a novel acidic superantigenic toxin produced by a T1 strain of Streptococcus pyogenes.

Streptococcus pyogenes T1 was previously found to produce an acidic mitogenic exotoxin, designated A beta, antigenically distinct from erythrogenic toxin type A (ETA) of strains T1 and NY5. Following chemical analysis and biological characterization, we have renamed this toxin streptococcal mitogenic exotoxin Z (SMEZ). Physicochemical separation of SMEZ from ETA was successfully performed on a hydrophobic chromatograph. The isoelectric point was pH 5.3, and the molecular size was estimated to be 28 kDa. These values were similar to those of ETA, but the amino acid composition and the NH2-terminal sequence of SMEZ were distinct from those of any mitogenic exotoxins hitherto described. Its mitogenic activity was found to be more potent than that of ETA in rabbit lymphocyte cultures. A specific antiserum raised against SMEZ did not cross-react with ETA, ETB, or ETC in the neutralization tests of mitogenic and erythrogenic activities. Its superantigenic nature was evident from the reverse transcriptase PCR findings of the T-cell receptor Vbeta profiles of rabbit lymphocytes stimulated in vitro. The Vbeta 8 subfamily was unique to SMEZ, while the Vbeta 2 and 6 subfamilies were found to be common among lymphocytes stimulated with ETA, ETB, ETC, or SMEZ. The results from this study provide an additional example of the diversity that exists among mitogenic or superantigenic exotoxins of streptococcal origin.

Animals↗

Immunohistochemical and ultrastructural examination of smooth muscle cells in aortocoronary saphenous vein grafts.

In this study, phenotypic modulation and remodulation of smooth muscle cells and associated intermediate filament expression were demonstrated by means of immunohistochemistry and ultrastructure to understand the development of intimal hyperplasia in aortocoronary saphenous vein grafts. In nongrafted saphenous veins, all smooth muscle cells expressed vimentin and desmin and were of a contractile form. In saphenous vein grafts showing stenotic intimal hyperplasia (luminal stenosis < 75%), expression of desmin was notably lower, whereas that of vimentin was higher. The cells were shown to be of a synthetic phenotype, suggesting modulation from the original contractile form. In saphenous vein grafts showing occlusive intimal hyperplasia (luminal stenosis > 76%), desmin expression in smooth muscle cells was increased again, and such cells were of a contractile form, suggesting remodulation from the synthetic phenotype. Some of the smooth muscle cells of the synthetic phenotype were positive for an antibody against proliferation cell nuclear antigen. Smooth muscle cells of the contractile form were negative for this antibody. The study suggests that smooth muscle cells of synthetic phenotype are highly responsible for "growing" intimal hyperplasia of aortocoronary saphenous vein grafts.

Actins↗