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Biomedical subjects

Toru Kubota

Publications and source records attributed to Toru Kubota.

65 records · Page 4Linked to original sources

Trends in antimicrobial susceptibility of the Streptococcus milleri group.

A collection of 114 clinical Streptococcus milleri group (SMG) strains at the Ryukyu University Hospital obtained in 1999 and 2000, was identified and tested for susceptibility to 12 antibiotics. The percentage of strains with intermediate susceptibility to penicillin G was relatively high (14%). Cefaclor and cefotiam, with a MIC 90 of 2 microg/ml, were less active than cefotaxime. Strains nonsusceptible to erythromycin, clindamycin, and azithromycin were found with a frequency of 8%, 5%, and 4%, respectively. Almost all of the SMG strains were susceptible to fluoroquinolones (except for 1% of the strains nonsusceptible to levofloxacin), and sitafloxacin (DU-6859a) was the most active agent among the 12 tested antibiotics.

Anti-Bacterial Agents↗

Improved functional reserve of hypertrophied contra lateral liver after portal vein ligation in rats.

BACKGROUND/AIMS: We assessed the functional capacity of hypertrophied liver after portal vein ligation (PL) in a test group of rats compared to a control group (without PL) having the same size liver. METHODS: The portal veins of the left and median lobes in the test group were ligated in an initial operation. Four days after the PL, the liver volume of the posterior caudate lobe (5%) increased two-fold, accounting for 10% of the liver. Then a 90% hepatectomy was performed, leaving only the hypertrophied posterior caudate lobe. Rats in a sham group underwent a 90% hepatectomy 4 days after having laparotomy, leaving the normal anterior and posterior caudate lobes (10%). RESULTS: The survival rate for the PL group was significantly higher than for the sham group at 4 days after hepatectomy (56.3 and 26.7%, P<0.05). The regeneration ratio and the proliferating cell nuclear antigen (PCNA) labeling index in the PL group was markedly higher than in the sham group 24h after hepatectomy. CONCLUSIONS: Hypertrophied liver at 4 days after PL still showed liver regeneration. Regenerating liver provided greater tolerance for extended hepatectomy than normal liver. This is because of the induced rapid regeneration of the remaining liver after hepatectomy.

Adenosine Triphosphate↗

Association of mumps virus V protein with RACK1 results in dissociation of STAT-1 from the alpha interferon receptor complex.

It has been reported that mumps virus protein V or the C-terminal Cys-rich region of protein V (Vsp) is associated with blocking of the interferon (IFN) signal transduction pathway through a decrease in STAT-1 production. The intracellular target of the V protein was investigated by using a two-hybrid screening system with Vsp as bait. Full-length V protein and Vsp were able to bind to RACK1, and the interaction did not require two WD domains, WD1 and WD2, in RACK1. A significant interaction between V protein and RACK1 was also demonstrated in cells persistently infected with mumps virus (FLMT cells), and the formation of the complex was not affected by treatment with IFN. On the other hand, in uninfected cells, STAT-1 was associated with the long form of the beta subunit of the alpha IFN receptor, and this association was mediated by the function of RACK1 as an adaptor protein. Immunoprecipitation and glutathione S-transferase pull-down experiments revealed that the association of RACK1 or mumps virus V protein with the IFN receptor was undetectable in mumps virus-infected cells. Furthermore, RACK1 interacted with mumps virus V protein with a higher affinity than STAT-1 did. Therefore, it is suggested that mumps virus V protein has the ability to interact strongly with RACK1 and consequently to bring about the disruption of the complex formed from STAT-1, RACK1, and the IFN receptor.

Cells, Cultured↗

C-terminal region of STAT-1alpha is not necessary for its ubiquitination and degradation caused by mumps virus V protein.

Constitutive levels of production of STAT-1 were reduced by 10 h postinfection (p.i.) and significantly lost by 24 h p.i. in FL cells acutely infected with mumps virus (MuV). This result was consistent with that observed in previous studies and experiments with cells persistently infected with MuV (FLMT cells). There was a marked decrease in the amount of STAT-1 in cells expressing MuV accessory protein V (MuV-V). Furthermore, single amino acid substitutions in the Cys-rich region of V protein (Vc189a, Vc207a, and Vc214a) showed that each cysteine residue plays an important role in the decrease in STAT-1 production, but substitution of a histidine residue at amino acid position 203 had no effect. These events and the resultant suppression of the alpha interferon (IFN-alpha) response were confirmed by a luciferase reporter gene assay with five tandem repeats of the IFN-alpha-stimulated response element as an enhancer element of the firely luciferase gene. STAT-1 production was restored and detectable in FLMT cells treated with a proteosome inhibitor, such as MG132 or lactacystin. In the presence of MG132, ubiquitination of STAT-1 and the interaction of MuV-V with STAT-1 were demonstrated in FLMT cells by immunoprecipitation with anti-STAT-1 antibody. The same results for the interaction and ubiquitination were obtained in experiments with an expression vector for a C-terminal deletion mutant of STAT-1. The truncated STAT-1 molecules were degraded in the presence of MuV-V. Therefore, the C-terminal region (transcriptional activation and Src homology 2 domains) of STAT-1 is not necessary for its degradation caused by MuV-V. Our data suggest that MuV-V promotes ubiquitination and degradation of STAT-1.

Amino Acid Sequence↗

Involvement of inducible nitric oxide synthase in cardiac dysfunction with tumor necrosis factor-alpha.

Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor (TNF)-alpha develop dilated cardiomyopathy with myocardial inflammation. The purpose of this study was to investigate the role of nitric oxide (NO) in this mouse model of cardiomyopathy. Female TG and wild-type mice at the age of 10 wk were studied. The expression and activity of inducible NO synthase (iNOS) were significantly increased in the TG myocardium, whereas those of endothelial NOS were not altered. The majority of the iNOS protein was isolated in the interstitial cells. The selective iNOS inhibitor (1S,5S,6R,7R)- 7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0]heptane hydrochloride (ONO-1714) was used to examine the effects of iNOS induction on myocardial contractility. Echocardiography and left ventricular pressure measurements were performed. Both fractional shortening and the maximum rate of rise of left ventricular pressure were significantly suppressed in TG mice. Although ONO-1714 did not change hemodynamic parameters or contractility at baseline, it significantly improved beta-adrenergic inotropic responsiveness in TG mice. These results indicate that induction of iNOS may play an important role in the pathogenesis of cardiac dysfunction in this mouse model of cytokine-induced cardiomyopathy.

Adrenergic beta-Agonists↗

Strain-specific patterns of autonomic nervous system activity and heart failure susceptibility in mice.

Transgenic mice are widely used to study cardiac function, but strain-dependent differences in autonomic nervous system activity (ANSA) have not been explored. We compared 1) short-term pharmacological responses of cardiac rhythm in FVB vs. C57Black6/SV129 wild-type mice and 2) long-term physiological dynamics of cardiac rhythm and survival in tumor necrosis factor (TNF)-alpha transgenic mice with heart failure (TNF-alpha mice) on defined backgrounds. Ambulatory telemetry electrocardiographic recordings and response to saline, adrenergic, and cholinergic agents were examined in FVB and C57Black6/SV129 mice. In FVB mice, baseline heart rate (HR) was higher and did not change after injection of isoproterenol or atropine but decreased with propranolol. In C57Black6/SV129 mice, HR did not change with propranolol but increased with isoproterenol or atropine. Mean HR, but not indexes of HR variability, was an excellent predictor of response to autonomic agents. The proportion of surviving animals was higher in TNF-alpha mice on an FVB background than on a mixed FVB/C57Black6 background. The homeostatic states of ANSA are strain specific, which can explain the interstrain differences in mean HR, pharmacological responses, and survival of animals with congestive heart failure. Strain-specific differences should be considered in selecting the strains of mice used for transgenic and gene targeting experiments.

Adrenergic alpha-Antagonists↗

Caudate lobectomy combined with resection of the inferior vena cava and its reconstruction by a pericardial autograft patch.

A 53-year-old woman with remnant liver metastasis originating from colon cancer was referred to our department. She underwent successful caudate lobectomy combined with resection of the inferior vena cava (IVC), including reconstruction with a pericardial autograft patch. IVC clamping was performed between the IVC below the confluence of the left hepatic vein and the infrahepatic IVC in order to preserve the hepatic circulation. After 18 months, the graft was patent and there was no sign of recurrence. A part of the pericardium used as an autograft for patch repair of the defect of the IVC was very useful because it was easily available, required only division of the diaphragm, and was of sufficient length and width.

Chemotherapy, Adjuvant↗

Myocarditis associated with visceral larva migrans due to Toxocara canis.

A 26-year-old man who was diagnosed with myocarditis presented eosinophilia after having eaten raw meat several times before the admission. Since the antibody titer against Toxocara canis was high, we diagnosed that he had visceral larva migrans due to Toxocara canis associated with myocarditis and eosinophilia. He was then treated with oral albendazole and prednisolone for 4 weeks and eosinophil count and hepatic enzymes were normalized along with the decrease in the antibody titer. We consider that his myocarditis was probably caused by direct larval migration and/ or by hypersensitivity reaction, for which combined therapy with albendazole and prednisolone was effective.

Adult↗

Contrast-enhanced sonography of small pancreatic mass lesions.

OBJECTIVE: To evaluate the usefulness of contrast-enhanced wideband harmonic gray scale sonography in assessing the vascularity of small pancreatic mass lesions. METHODS: Twenty-five patients with 25 pancreatic mass lesions (20 pancreatic carcinomas, 1 islet cell tumor, 1 malignant lymphoma, and 3 focal inflammatory pancreatic masses due to chronic pancreatitis) were examined. All patients held their breath for 20 to 50 seconds after injection of a contrast agent while the vascularity of the tumor was observed on contrast-enhanced wideband harmonic gray scale sonography (early phase). We then monitored the tumor enhancement 60 to 120 seconds after the injection while the patients held their breath for a few seconds (delayed phase). RESULTS: All 20 (100%) of the pancreatic carcinomas showed no contrast enhancement in the early phase. Fifteen (75%) of the 20 pancreatic carcinomas also showed no contrast enhancement in the delayed phase. The remaining 5 (25%) pancreatic carcinomas showed mild enhancement in the peripheral regions of the tumor in the delayed phase. The other pancreatic masses showed mild or pronounced enhancement throughout the entire lesions in both the early and delayed phases. CONCLUSIONS: Contrast-enhanced wideband harmonic gray scale sonography is a useful tool for differentiating pancreatic carcinomas from focal inflammatory pancreatic masses or hypervascular pancreatic tumors.

Aged↗

Pharmacologic preconditioning effects: prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver.

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.

Alprostadil↗

Middle hepatic vein tributary reconstruction could not act as a complete substitute for an entirely preserved middle hepatic vein.

BACKGROUND/AIMS: The necessity of the middle hepatic vein for living donor liver transplantation using right lobe graft is still controversial. METHODOLOGY: We reviewed 7 long-term surviving right-lobe recipients in whom middle hepatic vein tributaries were not reconstructed (group A, n=4) or were reconstructed (group B, n=3). Volume regeneration of the right paramedian (segments V+VIII) and right lateral (segments VI+VII) sectors was assessed by computed tomography at 3, 6, 9, and 12 postoperative months. The right paramedian sector was further subdivided into the ventral portion in relation to the anterior branch of the right portal vein and dorsal portion. RESULTS: The volume regeneration ratio was significantly lower in group A than in group B persistently after 6 postoperative months in regard to the right paramedian sector, the dorsal portion, and especially the ventral portion (0.64 +/- 0.19 vs. 1.22 +/- 0.17, p=0.034, 12 postoperative months). However, volume regeneration was impaired in the ventral portion as compared to other areas in group B. CONCLUSIONS: In conclusion, middle hepatic vein tributary reconstruction improves the volume regeneration of the right paramedian sector in right lobe living donor liver transplantation However, it could not act as a complete substitute for an entirely preserved middle hepatic vein.

Adolescent↗