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Biomedical subjects

T Kurata

Publications and source records attributed to T Kurata.

410 records · Page 23Linked to original sources

Localization of woodchuck hepatitis virus in the liver.

Localization of woodchuck hepatitis virus in liver tissue from 10 infected woodchucks was investigated immunohistochemically and ultrastructurally. Woodchuck hepatitis virus surface antigen was detected by immunoperoxidase methods in the cytoplasm of hepatocytes with a fine granular and/or inclusion body appearance. Woodchuck hepatitis virus surface antigen positive hepatocytes were often found in the peripheral zone of hepatic lobules. In contrast to human hepatitis B core antigen, woodchuck hepatitis virus core antigen was observed only in the cytoplasm of hepatocytes, but not in the nuclei. In hyperplastic foci, woodchuck hepatitis virus antigen-positive hepatocytes were found in 3 of 8 animals. Furthermore, in 1 of 5 animals with hepatocellular carcinoma, woodchuck hepatitis virus surface antigen and woodchuck hepatitis virus core antigen were present in carcinoma cells. Electron microscopic examination revealed many filamentous structures (18 to 20 nm in diameter) in the cisternae of the endoplasmic reticulum. Noncoated core particles (18 to 20 nm in diameter) were found in the cytoplasm of the hepatocytes, but not in the nuclei. The coated particles (42 to 45 nm in diameter) were observed in the cisternae of the endoplasmic reticulum. These coated particles were shown to be morphologically identical to the virus particles in serum. These results indicate that woodchuck hepatitis virus core antigen is produced and assembled mainly in the cytoplasm of hepatocytes, and seems to be rapidly assembled into virion. The similarity of woodchuck hepatitis virus infection to human hepatitis B virus infection makes the woodchuck an excellent experimental model for the study of hepadna virus oncogenesis.

Animals↗

Mutants of Escherichia coli heat-labile enterotoxin as an adjuvant for nasal influenza vaccine.

The effectiveness and safety of known mutants of Escherichia coli heat-labile enterotoxin (LT) as an adjuvant for nasal influenza vaccine were examined. Six mutants, called LT7K (Arg to Lys), LT61F (Ser to Phe), LT112K (Glu to Lys), LT118E (Gly to Glu), LT146E (Arg to Glu) and LT192G (Arg to Gly) were constructed by the replacement of one amino acid at one position of the A1 subunit to another using site-directed mutagenesis. All mutants were confirmed to be less toxic than wild-type LT when analyzed using Y-1 adrenal cells in vitro. When influenza vaccine was administered intranasally with LT7K and LT192G, BALB/c mice developed high levels of serum and local antibodies to the HA molecules. The adjuvant activity of these mutant LTs corresponded to that of wild-type LT when 1 microgram of these mutant LTs (or wild-type LT) was coadministered with the vaccine. From the point of view of safety, LT7K was considered to be the most potent mucosal adjuvant and was examined in more detail. The adjuvant activity of the mutant was lowered more rapidly with a decrease in dose than was that of wild-type LT. The low level of adjuvant of a relatively small amount of LT7K was heightened by adding LTB to the mutant LT. These results suggest that LT7K supplemented with LTB can be used as a less toxic, effective adjuvant for nasal influenza vaccine.

Adjuvants, Immunologic↗

Varicella zoster virus antigens in the epidermis of patients with herpes zoster before and after treatment with acyclovir: an immunohistochemical study.

Using a monoclonal antibody to varicella zoster virus (VZV), an immunohistochemical study was performed before and after treatment with acyclovir (750 mg/day intravenously for 5 - 7 days) to investigate the distribution of VZV antigens in the epidermis of four in-patients with herpes zoster, and to correlate their presence with clinical manifestations of the disease. Biopsy specimens were obtained from epidermal lesions on admission to hospital prior to acyclovir administration, and again following treatment. In all cases, VZV antigens were found extensively in the erythematous and vesicular lesions before treatment, but they were not detected 5 - 7 days later in the ulcerative, crusted or pigmented lesions after acyclovir therapy. Further controlled studies will be necessary to compare the distribution of epidermal VZV antigens in acyclovir-treated patients with that in a placebo group to determine whether the loss of VZV antigens was due to acyclovir or to a natural decrease over time.

Acyclovir↗

Cerivastatin induces carotid artery plaque stabilization independently of cholesterol lowering in patients with hypercholesterolaemia.

To prevent cardiovascular events in hyperlipidaemic patients, plaque stabilization by inhibition of localized inflammatory reactions in the blood vessels is important in addition to cholesterol lowering. Cerivastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin), has more potent enzyme-inhibitory effects than other statins and has also been reported in vitro to inhibit, at low concentrations, various inflammatory reactions due to plaque instability. Cerivastatin was therefore administered over 12 months to five patients with hypercholesterolaemia and atherosclerotic plaque diagnosed by ultrasonography of the carotid artery, and changes in the plaque composition were determined. The mean cholesterol level decreased over the study period, although not significantly. However, the mean percentage of fibrous matrix of the plaque increased significantly from a mean of 11.2 +/- 7.7% at study entry to 18.3 +/- 5.9% at the end of the study. Additionally, the mean maximum plaque height was significantly reduced from 3.7 +/- 0.9 mm to 3.0 +/- 0.7 mm. These results indicate that cerivastatin induces plaque stability independently of cholesterol lowering.

Aged↗

Cochlear changes after herpes simplex virus infection.

After direct inoculation of herpes simplex virus (HSV) into the scala tympani of the guinea pig, the tectorial membrane showed various morphological changes: atrophy, roll-up and dot formation. Immunofluorescent and electronmicroscopic studies revealed that the changes were due to HSV infection. The findings were compared with those observed in the temporal bones of a 77-year-old patient who suffered from sudden deafness. The tectorial membranes of both temporal bones showed various changes identical with those observed in experimental viral labyrinthitis. This supports the view that sudden deafness in this particular patient was of viral origin. In the animal experiment, HSV antigen could be detected from the cochlea of the non-inoculated side, which was morphologically normal. Further study is required to reactivate HSV in the cochlea with latent infection. This animal can probably be used as an animal model for sudden deafness.

Aged↗

Experimental labyrinthitis in rats caused by infecting with virus causing hemorrhagic fever with renal syndrome (HFRS).

Acute and persistent viral infection of the inner ear of rats was induced with hemorrhagic fever with renal syndrome (HFRS) virus following intraperitoneal inoculation. Newborn (within 24 h after birth) rats were inoculated intraperitoneally (i.p.) with HFRS virus (B-1 strain), and the cochlea was examined using an immunohistochemical technique for the localization of viral antigens 1 week (acute infection) and 1 year (persistent infection) after infection. Virus-specific antigens were detected in the inner ear structures of the rats suffering from both acute and persistent infection. Morphological changes in the inner ear structures of these rats were observed, with hemorrhage and infiltration of lymphocytes and macrophages. Moreover virus could be isolated from the blood of all infected rats. In the present study, we have proved that HFRS virus can infect the inner ear via the viremia.

Animals↗

Trends in antimicrobial-drug resistance in Japan.

Multidrug resistance in gram-positive bacteria has become common worldwide. In Japan until recently, gram-negative bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Serratia marcescens were controlled by carbapenems, fluoroquinolones, and aminoglycosides. However, several of these microorganisms have recently developed resistance against many antimicrobial drugs.

Drug Resistance, Microbial↗

Demonstration of acid phosphatase activity in antigenic glycoprotein fractions obtained from the culture filtrate of Pseudomonas pseudomallei.

Pseudomonas pseudomallei, the causative microorganism of melioidosis, was grown in Mueller-Hinton liquid medium, and glycoprotein fractions were separated from the culture filtrate by ammonium sulfate precipitation, gel-filtration with Sephadex G-75, and column chromatography with DEAE-cellulose. The fractions revealed acid phosphatase activity, and reacted to the sera from melioidosis patient in gel-diffusion precipitation assay.

Acid Phosphatase↗

Serosurveillance for double infection with Pseudomonas pseudomallei in tuberculous patients.

The serosensitivity to Pseudomonas pseudomallei antigen in pulmonary tuberculous patients was surveyed in Ubon Ratchathani Province, a melioidosis-endemic and tuberculosis-prevalent area in Thailand. Indirect hemagglutination assay (IHA) and indirect immunofluorescent assay (IFA) for IgM and IgG were employed for the measurement of antibody levels, with cut-off points set at 1:160, 1:8, and 1:32, respectively. Retrospective protocol survey of clinical data was also conducted. From these studies, however, no evidence was obtained to show that tuberculous patients have a disposition to acquire double-infected with P. pseudomallei and to develop melioidosis. The serosensitivity was never higher than that of the general population of the province as represented by healthy blood donors, nor related with the clinical severeness. Tuberculosis and melioidosis appear to be mutually independent diseases without showing interrelated prevalence in the endemic area.

Antibodies, Bacterial↗

A preliminary survey for human immunodeficient virus (HIV) infections in tuberculosis and melioidosis patients in Ubon Ratchathani, Thailand.

A preliminary survey was conducted for the prevalence of HIV infections in pulmonary tuberculosis and melioidosis patients in Ubon Ratchathani province, in Thailand, the second largest province in population which supplies labors to Bangkok metropolis. In this province, tuberculosis is prevalent in a higher rate than in most other provinces and melioidosis is endemic. Four HIV-seropositives were found in a total of 551 suspected and culture-positive cases of pulmonary tuberculosis, while no HIV-seropositive was found in 121 melioidosis patients. In view of the rapidly expanding HIV-infections in Thailand, a strict watch will be needed on the future epidemiological status of HIV-infection in tuberculous patient.

Antibodies, Bacterial↗

Computed tomography during arterial portography under temporary balloon occlusion of the hepatic artery: evaluation of pseudolesions caused by arterio-portal venous shunts.

BACKGROUND: Computed tomography during arterial portography (CTAP) under temporary balloon occlusion of the hepatic artery (BOHA-CTAP) was introduced to evaluate pseudolesions caused by portal venous impairments such as arterioportal shunt and tumor thrombus. METHODS: BOHA-CTAP was performed in seven patients with hepatocellular carcinoma and correlated with clinical outcomes. For patients with wedge-shaped defects suggestive of pseudolesions, BOHA-CTAP was obtained by a 5-F balloon occlusion catheter into the proper hepatic artery through the second 5-F introducer inserted into the common femoral artery a few centimeters below the first 5-F sheath for CTAP. RESULTS: Eight pseudolesions were determined clinically on follow-up CT, ultrasonography, or magnetic resonance imagings. On BOHA-CTAP, five of the eight pseudolesions were eliminated, and two were diminished in comparision with conventional CTAP. One wedge-shaped defect due to tumor thrombus in the portal vein did not show any change. CONCLUSION: BOHA-CTAP can reduce pseudolesions caused by portal venous impairments and enable the demarcation of the true tumors.

Aged↗

Stereoselective glucuronidation of ofloxacin in rat liver microsomes.

The stereoselective glucuronidation of ofloxacin [(+/-)-OFLX], a new quinolone antibacterial agent, was studied in vitro using rat liver microsomes. OFLX glucuronidation exhibited Michaelis-Menten kinetics in rat liver microsomes. Stereoselective glucuronidation of the optical enantiomers occurred. S-(-)-OFLX glucuronide was produced 7-fold more than R-(+)-OFLX glucuronide with little or no difference in the values of KM of the enantiomers. The value of Vmax/KM for the glucuronide conjugate of S-(-)-OFLX was 8-fold greater than for the conjugate of R-(+)-OFLX. These results demonstrate that OFLX undergoes stereoselective glucuronidation in vitro. Moreover, we studied the in vivo interaction between enantiomers of OFLX in rats to clarify the effects of R-(+)-OFLX on the metabolism and disposition of S-(-)-OFLX. When the racemate [(+/-)-OFLX (20 mg/kg)] or single enantiomer [S-(-)-OFLX (10 mg/kg)] is administered iv to the rat, the serum concentrations of S-(-)-OFLX were higher after racemate administration than those after enantiomer administration, although the dose of S-(-)-OFLX was identical in both cases. These results indicate that R-(+)-OFLX may compete with S-(-)-OFLX in the in vivo glucuronidation. Furthermore, the results of the enantiomeric inhibition study showed that R-(+)-OFLX competitively inhibited S-(-)-OFLX glucuronidation in vitro with a Ki value of 2.92 mM.

Animals↗

Lack of susceptibility of various primates and woodchucks to hepatitis C virus.

Five different species of primates including cynomolgus monkey, rhesus monkey, green monkey, Japanese monkey, and doguera baboon and woodchucks were inoculated intravenously with infectious serum from a chimpanzee infected with hepatitis C. Serum samples obtained weekly from these animals were negative for hepatitis C virus RNA and anti-HCV during six months following inoculation. Furthermore, serum alanine aminotransferase remained within normal limits, and normal liver histology was seen. This study indicates that these primates and woodchucks do not appear to be susceptible to hepatitis C virus.

Animals↗

Chronopharmacology of etoposide given by low dose prolonged infusion in lung cancer patients.

We examined the chronopharmacology of prolonged etoposide administration by intravenous infusion over 14 days in 9 patients with lung cancer. Blood samples were obtained every 4 hours between 24 hours and 48 hours after initiation of the infusion. Using the unpaired t-test, the percentage plasma etoposide concentration at 09:00 hours calculated from the 24 hour average value, was significantly higher than that at 21:00 hours (p = 0.024). However, neither ANOVA nor cosinor analysis revealed any significant effect of sampling time (ANOVA: p = 0.29, cosinor analysis: p = 0.46).

Adult↗