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Biomedical subjects

T Kamiyama

Publications and source records attributed to T Kamiyama.

At least 19 recordsLinked to original sources
PubMed2003

Immune response to Japanese rabies vaccine in domestic dogs.

To evaluate the immune response induced by Japanese rabies vaccine for veterinary use as international units (IU), we measured levels of rabies antibody in serum samples from dogs by the rapid fluorescent focus inhibition test (RFFIT). In dogs immunized with a reference vaccine (potency level of 3.1 IU/ml), prepared by the same method as that used to produce commercial vaccine, and its dilutions (1 : 2 or 1 : 4), neutralizing-antibody levels increased to 1.0-2.0 IU/ml over a period of 1 month and then decreased to 0.2-1.5 IU/ml over a period of 1 year after the first vaccination and showed a remarkable increase to 12-47 IU/ml after the second vaccination. Sixty-five (74.7%) of the 87 serum samples from domestic dogs that were tested were seropositive (> or =0.1 IU/ml). However, the seropositive rate in dogs less than 1-year old at the time of vaccination was low (57.1%), and the antibody levels in these dogs were not sufficiently high for the rabies antibody titre in serum to be maintained for 1-year. Levels of rabies antibody in all serum samples were also measured by the virus neutralizing test (VNT), and a strong correlation (r > 0.95) was found between the results of the RFFIT and those of the VNT.

Animals↗
PubMed2002

In vitro and in vivo activities of anti-influenza virus compound T-705.

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been found to have potent and selective inhibitory activity against influenza virus. In an in vitro plaque reduction assay, T-705 showed potent inhibitory activity against influenza A, B, and C viruses, with 50% inhibitory concentrations (IC(50)s) of 0.013 to 0.48 microg/ml, while it showed no cytotoxicity at concentrations up to 1,000 microg/ml in Madin-Darby canine kidney cells. The selectivity index for influenza virus was more than 2,000. It was also active against a neuraminidase inhibitor-resistant virus and some amantadine-resistant viruses. T-705 showed weak activity against non-influenza virus RNA viruses, with the IC(50)s being higher for non-influenza virus RNA viruses than for influenza virus, and it had no activity against DNA viruses. Orally administered T-705 at 100 mg/kg of body weight/day (four times a day) for 5 days significantly reduced the mean pulmonary virus yields and the rate of mortality in mice infected with influenza virus A/PR/8/34 (3 x 10(2) PFU). These results suggest that T-705 may be a compound that is useful and highly selective against influenza virus infections and that has a mode of action different from those of commercially available drugs, such as amantadine, rimantadine, and neuraminidase inhibitors.

Amides↗
PubMed2001

Feeding characteristics of two tintinnid ciliate species on phytoplankton including harmful species: effects of prey size on ingestion rates and selectivity.

The feeding abilities of two tintinnid ciliates, Favella ehrenbergii and Favella taraikaensis, on 10 species of flagellates including harmful marine algae were examined under single prey conditions, and selective feeding of F. taraikaensis on two species of algae of different sizes was investigated under mixed prey conditions. Ingestion rates calculated from the rate of increases of auto-fluorescent particles inside food vacuoles in individuals ranged from 0.5 to 22.1 cells ind(-1) h(-1) for F. ehrenbergii and from 0.8 to 44.9 cells ind(-1) h(-1) for F. taraikaensis on nine species of prey algae. Significant ingestion rates of both Favella species could not be detected on Heterosigma akashiwo, although some individuals of both species were observed ingesting H. akashiwo in the initial incubation period. The relationship between prey cell volume and ingestion rate could be expressed mathematically for both Favella species, indicating that it is possible to estimate the potential feeding activity of each Favella species on specific algae using an equation, and may be applicable to evaluate the food value of prey alga for both Favella species. When F. taraikensis was fed mixtures of H. circularisquama and Pavlova lutheri, significant ingestion rates of H. circularisquama by F. taraikaensis could not be measured when H. circularisquama accounted for less than 20% of the other prey biomass. However, clear selectivity for H. circularisquama was observed when H. circularisquama reached and exceeded 34% of the other prey biomass. Under mixed prey conditions, it is likely that the selectivity of F. taraikaensis is stronger for larger prey compared to prey algae with a size near the lower limit on which F. taraikaensis can feed.

Journal Article↗
PubMed2001

Observation of d(x2-y2)-like superconducting gap in an electron-doped high-temperature superconductor.

High-resolution angle-resolved photoemission spectroscopy of the electron-doped high-temperature superconductor Nd(2-x)Ce(x)CuO4 (x = 0.15, transition temperature T(c) = 22 K) has found the quasiparticle signature as well as the anisotropic d(x2-y2)-like superconducting gap. The spectral line shape at the superconducting state shows a strong anisotropic nature of the many-body interaction. The result suggests that the electron-hole symmetry is present in the high-temperature superconductors.

Journal Article↗
PubMed2001

Nicorandil, a potent cardioprotective agent, reduces QT dispersion during coronary angioplasty.

BACKGROUND: Previous studies have found that ST-segment elevation and QT dispersion are smaller in second coronary occlusions than in first occlusions, a trend that suggests ischemic preconditioning. It has not been established whether nicorandil reduces ST-segment elevation and QT dispersion during coronary angioplasty. METHODS AND RESULTS: Thirty patients with stable angina undergoing coronary angioplasty in the proximal left anterior descending artery were randomly assigned to one of two groups, receiving either 5 mg oral nicorandil 3 times daily (n = 15) or placebo (n = 15). In the control patients, the total ST-segment elevation decreased from 14 +/- 3 mm during the first inflation to 7 +/- 2 mm during the second inflation (P < .01). In contrast, in the nicorandil-treated patients, the total ST-segment elevation during the second inflation was roughly equivalent to that during the first inflation (8 +/- 3 mm vs 8 +/- 3 mm, P = not significant). After the first reperfusion, a significantly smaller increase in QT dispersion was observed in the nicorandil-treated patients than in the control patients (43 +/- 15 ms vs 54 +/- 15 ms, P < .001). However, after the second reperfusion, QT dispersion was similar for the two groups (32 +/- 15 ms vs 34 +/- 13 ms, P = not significant). CONCLUSIONS: Nicorandil may precondition the myocardium and may prevent the occurrence of ventricular arrhythmias after coronary reperfusion by suppressing the increase in QT dispersion.

Angina Pectoris↗
PubMed2001

Risk factors for stiffness of the wall of the thoracic aorta in patients with mild atherosis.

Previous studies have suggested that aging is associated with progressive arterial stiffness and widening of the pulse pressure, and pulse pressure has been found to be a risk factor of cardiovascular diseases. However, the effects of age, blood pressure (including pulse pressure) or atherogenic factors on thoracic aortic wall stiffness in patients with mild atherosis are unclear, so the present study used transesophageal echocardiography to examine 103 consecutive patients with various cardiovascular diseases. The extent of atherosis was evaluated in terms of intima-medial thickness (IMT), and 2 indices of wall stiffness in the aorta were calculated: elastic modulus and stiffness parameter (beta). In subjects with mild atherosis (IMT <1.0mm), age, body mass index, systolic blood pressure, pulse pressure, triglyceride level, and hypertension were factors significantly associated with high wall stiffness, and multiple logistic stepwise analysis revealed that age, pulse pressure, and triglyceride level were particularly significant.

Adult↗
PubMed2000

Effect of ligand binding on the flexibility of dihydrofolate reductase as revealed by compressibility.

The partial specific volume, v, and adiabatic compressibility, beta(s), of Escherichia coli dihydrofolate reductase were measured at 30 degrees C in the presence of various ligands (folate, dihydrofolate, tetrahydrofolate, NADPH, NADP, methotrexate, and KCl). Binding of these ligands (binary and ternary complexes) brought about large changes of v (0.734-0.754 cm(3) g(-1)) and beta(s) (6. 6x10(-6)-9.8x10(-6) bar(-1)), keeping a linear relationship between the two parameters. The values of v and beta(s) increased with an increase in internal cavity, V(cav), and a decrease in accessible surface area, ASA, which were calculated from the X-ray crystal structures of the complexes. A large variation of V(cav) relative to ASA by ligand binding suggested that the cavity is a dominant factor and the effect of hydration might be small for the ligand-induced changes of v and beta(s). The beta(s) values of the binary and ternary complexes suggested a characteristic conformational flexibility of the kinetic intermediates in the enzyme reaction coordinate. Comparison of beta(s) with the cavity distribution in the crystal structures revealed that the flexibility of the intermediates was mainly determined by the total cavity volume with minor contributions of the number, position, and size of cavities. These results demonstrate that the compressibility is a useful measure of the conformational flexibility of the intermediates in the enzyme reaction and that the combined study of compressibility and X-ray crystallography gives new insight into the protein dynamics through the behavior of the cavities.

Escherichia coli↗
PubMed2000

Characterization of acyclovir susceptibility and genetic stability of varicella-zoster viruses isolated during acyclovir therapy.

We have characterized the susceptibility and genetic stability of varicella-zoster viruses (VZV) isolated from skin lesions of three patients with herpes zoster and six patients with varicella treated with conventional short-term acyclovir (ACV) administration. The susceptibilities to ACV of the serial isolates from the patients were examined, and there was no significant difference in the susceptibility to ACV among the isolates before and during the ACV treatment, indicating that conventional short-term ACV treatment did not generate ACV-resistant VZV infections. Polymerase chain reaction (PCR) analyses of these as well as seven thymidine kinase-deficient VZV strains derived from in vitro ACV treatment were carried out to examine their genomic stability. Five regions containing tandem direct reiterations (R1-R5) were amplified by PCR and compared, and the region containing the Pst I-site was also examined. PCR analyses demonstrated that the R1, R5 and the Pst I-sites were stable and useful in epidemiological studies even after ACV treatment. The R2, R3 and R4 sites were far less stable in these experimental conditions. In this paper we discuss the results of the PCR analyses with regard to the dynamics of VZV population in patients with VZV infection treated with conventional short-term ACV administration.

Acyclovir↗
PubMed2000

Novel immunogenicity of Oka varicella vaccine vector expressing hepatitis B surface antigen.

Recombinant Oka (ROka) varicella vaccine expressing hepatitis B surface antigen (HBsAg) and subunit HBsAg vaccine (SHV) were used as primary and booster HBsAg vaccines in 3 combinations (SHV-SHV, SHV-ROka, and ROka-SHV) in guinea pigs. Immune responses to HBsAg and varicella-zoster virus gE:gI were evaluated. The 3 combinations induced similar levels of the lymphocyte proliferation response to HBsAg. Of the 3 combinations, SHV-SHV induced the strongest antibody response to an "a" loop of HBsAg and to the whole HBsAg. Its ratio of antibody titer to this loop versus HBsAg was significantly higher than that in SHV-ROka, suggesting the supplementary recognition of the conformational epitope of HBsAg in SHV-ROka. SHV-ROka induced delayed-type hypersensitivity (DTH) to the HBsAg and gE:gI produced in infected cells. Thus, ROka induced DTH to HBsAg and enhanced recognition of the conformational epitope. ROka varicella vaccine may serve as a novel vaccine vector to induce a Th1-type immune response.

Animals↗
PubMed2000

Single amino acid substitutions in flexible loops can induce large compressibility changes in dihydrofolate reductase.

To address the effects of single amino acid substitutions on the flexibility of Escherichia coli dihydrofolate reductase (DHFR), the partial specific volume (v(o)) and adiabatic compressibility (beta(s)(o)) were determined for a series of mutants with amino acid replacements at Gly67 (7 mutants), Gly121 (6 mutants), and Ala145 (5 mutants) located in three flexible loops, by means of precise sound velocity and density measurements at 15 degrees C. These mutations induced large changes in v(o) (0.710-0.733 cm(3). g(-1)) and beta(s)(o) (-1.8 x 10(-6)-5.5 x 10(-6) bar(-1)) from the corresponding values for the wild-type enzyme (v(o)=0.723 cm(3). g(-1), beta(s)(o) = 1.7 x 10(-6) bar(-1)), probably due to modifications of internal cavities. The beta(s)(o) value increased with increasing v(o), but showed a decreasing tendency with the volume of the amino acid introduced. There was no significant correlation between beta(s)(o) and the overall stability of the mutants determined from urea denaturation experiments. However, a mutant with a large beta(s)(o) value showed high enzyme activity mainly due to an enhanced catalytic reaction rate (k(cat)) and in part due to increased affinity for the substrate (K(m)), despite the fact that the mutation sites are far from the catalytic site. These results demonstrate that the flexibility of the DHFR molecule is dramatically influenced by a single amino acid substitution in one of these loops and that the flexible loops of this protein play important roles in determining the enzyme function.

Amino Acid Substitution↗
PubMed2000

Association of human papillomavirus type 6 with a verruciform xanthoma.

We report a case of verruciform xanthoma (VX) associated with human papillomavirus (HPV) in a 67-year-old male. The patient had a pale-reddish, granular and verrucous tumor on the right side of his scrotum for four years. Histopathologic examination showed typical features of VX. HPV was detected by immunohistochemistry, electron microscopy, and PCR examinations. Ultrastructural examination revealed virus-like particles of 40-50 nm in the nucleus of the upper epidermal keratinocytes. HPV type 6a DNA was detected in lesional tissue by polymerase chain reaction and sequence analysis. To the best of our knowledge, this is the first case report of VX associated with HPV.

Aged↗
PubMed2000

UV-B irradiation increases susceptibility of mice to malarial infection.

We here examined whether exposure of mice to UV-B affected their susceptibility to the murine malaria parasite Plasmodium chabaudi. When BALB/c mice with depilated skin were irradiated with UV-B and subsequently infected with the parasite, 80 to 100% of the UV-B-irradiated mice died within 12 days of infection with a sublethal dose. In addition, UV-B irradiation of C57BL/10 (B-10) mice, which are otherwise naturally resistant to the parasites, rendered them susceptible, and 100% of irradiated B-10 mice died within 11 days postinfection. The level of plasma gamma interferon (IFN-gamma) in unirradiated B-10 mice at 5 days after infection increased to 566 pg/ml, whereas the UV-B exposure of mice impaired the production of IFN-gamma, which showed a maximum level of 65 pg/ml in response to the parasite infection. The maximum level of plasma interleukin-10 in UV-B-irradiated mice in response to the parasite infection was approximately 1,100 pg/ml, which was approximately fourfold higher than the maximum level in unirradiated control mice. When UV-B-irradiated B-10 mice were administered murine recombinant IFN-gamma after infection, the mice regained parasite resistance. These results demonstrated that the UV-B exposure of mice enhances the susceptibility to the malaria parasites and suggested that the enhanced susceptibility following UV-B exposure was mediated by impairment of IFN-gamma production in response to the parasite infection.

Animals↗
PubMed2000

Transfusion-acquired, autochthonous human babesiosis in Japan: isolation of Babesia microti-like parasites with hu-RBC-SCID mice.

We have isolated piroplasms from a patient who developed the first case of human babesiosis in Japan by using NOD/shi-scid mice whose circulating erythrocytes (RBCs) had been replaced with human RBCs (hu-RBC-SCID mice). Following inoculation of the patient's blood specimen into hu-RBC-SCID mice, parasites proliferated within the human RBCs in the mice, resulting in a high level of parasitemia. Parasite DNA was prepared from blood samples of the patient and the mice, and the nuclear small-subunit rRNA gene (rDNA) was amplified and sequenced. Both DNA samples gave rise to identical sequences which showed the highest degree of homology (99.2%) with the Babesia microti rDNA. Because the patient had received a blood transfusion before the onset of babesiosis, we investigated the eight donors who were involved. Their archived blood samples were analyzed for specific antibody and parasite DNA; only a single donor was found to be positive by both tests, and the parasite rDNA sequence from the donor coincided with that derived from the patient. The donor's serum exhibited a high antibody titer against the isolate from the patient, whereas it exhibited only a weak cross-reaction against B. microti strains isolated in the United States. We conclude that the first Japanese babesiosis case occurred due to a blood transfusion and that the etiological agent is an indigenous Japanese parasite which may be a geographical variant of B. microti. Our results also demonstrated the usefulness of hu-RBC-SCID mice for isolation of parasites from humans and for maintenance of the parasite infectivity for human RBCs.

Animals↗
PubMed2000

[Percutaneous mechanical thrombectomy for thrombosed vessels with a hydrolyser (hydrodynamic thrombectomy catheter): clinical experience].

A hydrodynamic thrombectomy catheter was prospectively evaluated for the treatment of thrombosed vessels. Seven patients (7 males: age range from 56 to 82 years; mean age: 79 years) presenting with acute or chronic occlusion of peripheral native arteries (n = 6) and dialysis shunt (n = 1) were treated with the hydrolyser (Cordis, Johnson and Johnson, Japan). Mean occlusion time was 135 days (range: 2-300 days), and mean thrombus length 16 cm (range: 5-20 cm). Removal of the thrombus was successful in five patients (71%), regardless of the length of the thrombus. Mean procedure time was 20 minutes (range: 15-30 minutes). No major complications occurred. Adjunctive thrombolysis was required for persistence of the residual thrombosed distal vessel in one patient. Adjunctive balloon angioplasty was performed in two patients (one native vessel and one dialysis shunt), and stent placement was performed in one patient (dialysis shunt). In two unsuccessful cases, the hydrolyser could not be advanced to the distal side because of the solid thrombus. Therefore, thrombolytic therapy was chosen. However, this therapy failed because the guidewire did not pass within the thrombus. Surgery was performed in these two patients. We conclude from this clinical experience that percutaneous thrombectomy with a hydrolyser is a promising technique for the treatment of thrombosed vessels. Especially in the acute stage of thrombosed occlusion, percutaneous thrombectomy with a hydrolyser is superior to thrombectomy with a Fogarty balloon catheter because of its shorter procedure time and fewer complications.

Acute Disease↗
PubMed2000

Cytofluorometric nuclear DNA content analysis of breast tissues after frozen section diagnosis.

OBJECTIVE: To establish a suitable method for measurement of nuclear DNA content in breast tissues from frozen storage after frozen section diagnosis. STUDY DESIGN: For fundamental research, rat liver samples preserved in a deep freezer were used. Four protocols were used (1. fixation with 70% ethanol followed by naked nuclei preparation; 2. fixation with 10% neutral buffered formalin followed by naked nuclei preparation; 3. preparation for naked nuclei prior to fixation with 70% ethanol; and 4. preparation for naked nuclei prior to fixation with 70% neutral buffered formalin). For clinical research, 13 separate fresh frozen breast tissue samples were analyzed after frozen section diagnosis. One contained a malignant phyllodes tumor (MPT) consisting of 2 components, benign epithelial cells and malignant stromal cells; 3 were benign tumors containing fibroadenoma; and 9 cases were carcinomas, consisting of 5 scirrhous, 3 papillotubular and 1 mucinous. RESULTS: Protocols 1, 2 and 3 were not suitable methods for our purpose because remaining cytoplasm or cohesive nuclei were observed. In protocol 4 the cytoplasm was completely undetectable, and nuclei were suitably separated for nuclear DNA content measurement. Benign epithelial cell component nuclei presented a diploid pattern, and the malignant stromal cell component nuclei indicated a euploid pattern in MPT. All 3 cases of benign constituents in fibroadenoma showed a diploid pattern, as did the 3 carcinoma cases (1 mucinous, 1 scirrhous and 1 papillary). Four scirrhous and 2 papillary carcinomas showed an aneuploid pattern. CONCLUSION: Our findings show that it is possible to measure nuclear DNA content of human frozen storage tissues after frozen section diagnosis.

Animals↗
PubMed1999

19-oxygenations of 3-deoxy androgens, potent competitive inhibitors of estrogen biosynthesis, with human placental aromatase.

Aromatase is a cytochrome P450 enzyme complex that catalyzes the conversion of androst-4-ene-3,17-dione (AD) to estrone through three sequential oxygenations of the 19-methyl group. To gain insight into the ability of 3-deoxy derivative of AD, compound 1, and its 5-ene isomer 4, which are potent competitive inhibitors of aromatase, to serve as a substrate, we studied their 19-oxygenation by human placental aromatase and the metabolites isolated were analyzed by gas chromatography-mass spectrometry. Inhibitors 1 and 4 were found to be oxygenated with aromatase to produce the corresponding 19-hydroxy derivatives 2 and 5 and 19-oxo derivatives 3 and 6 as well as the 17beta-reduced 19-hydroxy compounds 7 and 8. Kinetic studies indicated that the 5-ene steroid 4 was surprisingly a good substrate for the aromatase-catalyzing 19-oxygenation with the V(max) value of 45 pmol/min per mg prot which was approx. four times higher than that of the other. The relative K(m) value for steroids 1 and 4 obtained in this study is opposite from the relative K(i) value obtained previously in the inhibition study. The results reveal that there is a difference between a binding suitable for serving as an inhibitor of aromatase and a binding suitable for serving as a substrate of the enzyme in the 3-deoxy steroid series and the C-3 carbonyl group of AD is essential for a proper binding as a substrate to the active site of aromatase.

Androgens↗
PubMed1999

Polyol-induced molten globule of cytochrome c: an evidence for stabilization by hydrophobic interaction.

To address the contribution of hydrophobic interaction to the stability of molten globule (MG) of proteins, the effects of various polyols (ethylene glycol, glycerol, erythritol, xylitol, sorbitol, and inositol) on the structure of acid-unfolded horse cytochrome c were examined at pH 2, by means of circular dichroism (CD), partial specific volume, adiabatic compressibility, and differential scanning calorimetry (DSC). Addition of polyols induced the characteristic CD spectra of MG, the effect being enhanced with an increase in their concentration and chain length (the number of OH groups) of polyols except for ethylene glycol. The free energy change of MG formation by sorbitol was comparable with those for the salt-induced MG formation but the heat capacity change was negligibly small. The partial specific volume did not change within the experimental error but the adiabatic compressibility largely increased by MG formation. The sorbitol-induced MG showed a highly cooperative DSC thermogram with a large heat capacity change in comparison with the salt-induced one. These results demonstrate that polyols can stabilize the MG state of this protein through the enhanced hydrophobic interaction overcoming the electrostatic repulsion between charged residues. The stabilizing mechanism and structure of MG state induced by polyols were discussed in terms of the preferential solvent interactions and osmotic pressure of the medium, in comparison with the salt-induced one.

Calorimetry, Differential Scanning↗