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Biomedical subjects

C Takahashi

Publications and source records attributed to C Takahashi.

At least 19 recordsLinked to original sources

Identification of zonal flows in a toroidal plasma.

This Letter presents experimental confirmation of the presence of zonal flows in magnetically confined toroidal plasma using an advanced diagnostic system--dual heavy ion beam probes. The simultaneous observation of an electric field at two distant toroidal locations (approximately 1.5 m apart) in the high temperature (approximately 1 keV) plasma provides a fluctuation spectrum of electric field (or flow), a spatiotemporal structure of the zonal flows (characteristic radial length of approximately 1.5 cm and lifetime of approximately 1.5 ms), their long-range correlation with toroidal symmetry (n=0), and the difference in the zonal flow amplitude with and without a transport barrier. These constitute essential elements of turbulence-zonal flow systems, and illustrate one of the fundamental processes of structure formation in nature.

Journal Article↗

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↗

The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis.

Matrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling. We previously found that a membrane-anchored glycoprotein, RECK, negatively regulates MMP-9 and inhibits tumor invasion and metastasis. Here we show that RECK regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression, that mice lacking a functional RECK gene die around E10.5 with defects in collagen fibrils, the basal lamina, and vascular development, and that this phenotype is partially suppressed by MMP-2 null mutation. Also, vascular sprouting is dramatically suppressed in tumors derived from RECK-expressing fibrosarcoma cells grown in nude mice. These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis.

Animals↗

Extremely large group-velocity dispersion of line-defect waveguides in photonic crystal slabs.

We reveal experimentally waveguiding characteristics and group-velocity dispersion of line defects in photonic crystal slabs as a function of defect widths. The defects have waveguiding modes with two types of cutoff within the photonic band gap. Interference measurements show that they exhibit extraordinarily large group dispersion, and we found waveguiding modes whose traveling speed is 2 orders of magnitude slower than that in air. These characteristics can be tuned by controlling the defect width, and the results agree well with theoretical calculations, indicating that we can design light paths with made-to-order dispersion.

Journal Article↗

Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites.

Streptomyces avermitilis is a soil bacterium that carries out not only a complex morphological differentiation but also the production of secondary metabolites, one of which, avermectin, is commercially important in human and veterinary medicine. The major interest in this genus Streptomyces is the diversity of its production of secondary metabolites as an industrial microorganism. A major factor in its prominence as a producer of the variety of secondary metabolites is its possession of several metabolic pathways for biosynthesis. Here we report sequence analysis of S. avermitilis, covering 99% of its genome. At least 8.7 million base pairs exist in the linear chromosome; this is the largest bacterial genome sequence, and it provides insights into the intrinsic diversity of the production of the secondary metabolites of Streptomyces. Twenty-five kinds of secondary metabolite gene clusters were found in the genome of S. avermitilis. Four of them are concerned with the biosyntheses of melanin pigments, in which two clusters encode tyrosinase and its cofactor, another two encode an ochronotic pigment derived from homogentiginic acid, and another polyketide-derived melanin. The gene clusters for carotenoid and siderophore biosyntheses are composed of seven and five genes, respectively. There are eight kinds of gene clusters for type-I polyketide compound biosyntheses, and two clusters are involved in the biosyntheses of type-II polyketide-derived compounds. Furthermore, a polyketide synthase that resembles phloroglucinol synthase was detected. Eight clusters are involved in the biosyntheses of peptide compounds that are synthesized by nonribosomal peptide synthetases. These secondary metabolite clusters are widely located in the genome but half of them are near both ends of the genome. The total length of these clusters occupies about 6.4% of the genome.

Base Sequence↗

OX40 ligation enhances cell cycle turnover of Ag-activated CD4 T cells in vivo.

OX40 costimulates T cells, increases activated T cell longevity, and promotes memory acquisition. T cells activated in vivo with agonist anti-OX40 and ovalbumin have a unique pattern of survival and cell division compared to control cells, but are able to respond to recall Ag equally well. BrdU incorporation shows that early cellular division rates of the anti-OX40-treated and the control groups are similar. Nevertheless, more BrdU(+) Ag-specific T cells accumulate in lymphoid tissue upon anti-OX40 administration. Thus, OX40 ligation does not necessarily lead to increased cell cycle entry, but promotes the accumulation of dividing cells. However, CFSE staining shows that OX40 ligation allows cells to progress through more cellular division cycles, while control cells stall or die. Moreover, OX40 ligation leads to a proportional decrease in apoptotic Ag-specific T cells. Thus, OX40 ligation boosts immunity by promoting an increase in the number cell cycles completed, thereby increasing the life span of Ag-activated CD4 T cells.

Animals↗

Differential clonal expansion of CD4 and CD8 T cells in response to 4-1BB ligation: contribution of 4-1BB during inflammatory responses.

Cell surface proteins of the tumor necrosis factor (TNF) family of receptors have been intimately involved in inducing T cell death. A feature of these family members that is less well studied is their ability to rescue T cells from apoptosis. One such member is 4-1BB; an activation induced surface receptor on CD4 and CD8 T cells. This study demonstrates that the costimulatory effects of 4-1BB, which was found to enhance clonal expansion, required cross-linking of the receptor. The survival of the activated CD8 T cells following expansion was not associated with an increase in Bcl-2 expression. Provided that 4-1BB signaling was present, the amplification of activated CD8 T cell growth in vivo was independent of CD28 ligation. In vivo clonal expansion of activated CD4 T cells, however, was not as responsive to 4-1BB cross-linking. Moreover, 4-1BB-induced expansion was comparable to that mediated by LPS which can incite multiple costimulatory signals. Furthermore, LPS-mediated growth and survival of superantigen (SAg) stimulated T cells appeared to be partially dependent on interactions between 4-1BB and 4-1BB ligand (4-1BBL).

4-1BB Ligand↗

Observation of toroidal flow antiparallel to the drift direction in the hot electron mode plasmas in the compact helical system.

A toroidal flow antiparallel to the drift direction is observed in the hot electron mode plasmas when a large positive electric field and a sharp electron temperature gradient are sustained inside the internal transport barrier in the Compact Helical System. This toroidal flow reaches up to 5x10(4) m/s at the plasma center, and it is large enough to reverse the toroidal flow driven by a tangentially injected neutral beam. These observations clearly show the plasma favors flow in the minimum nablaB direction at the transport barrier.

Journal Article↗

Radiation therapy for loco-regionally recurrent esophageal cancer after surgery.

PURPOSE: To evaluate the treatment outcome of radiation therapy for 33 loco-regionally recurrent esophageal cancer patients. METHODS: Between 1988 and 1997, 33 patients with loco-regional recurrence of esophageal cancer after curative surgery received radiation therapy at an average total dose of 61 Gy. The site of recurrence was the supraclavicular region in 14 patients, the mediastinal region in 13 patients, and both the supraclavicular and mediastinal regions in six patients. If patients had ether distant metastasis or malignant pleural effusion, they were excluded from analysis. Patients who received prophylactic postoperative irradiation were also excluded from analysis. RESULTS: The median survival period was 7 months. The survival rates at 1, 2, and 3 years were 33, 15, and 12%, respectively. In univariate analysis, patients with a short time interval between surgery and recurrence (P=0.0098) and patients with recurrence in both the supraclavicular and mediastinal regions (P=0.036) had a worse prognosis. In multivariate analysis, the time interval between surgery and recurrence (P<0.001) and age (worse prognosis in younger patients, P=0.019) were the significant prognostic factors. Complete or partial responses were observed in nine (27%) and 21 (64%) of the patients, respectively. Changes in clinical symptoms, such as dysphagia, chest pain and back pain, could be evaluated in 11 patients, and improvement in symptoms was obtained in eight (73%) patients. CONCLUSIONS: The prognosis of patients who received radiation therapy for postoperative loco-regional recurrence of esophageal cancer is poor. However, there is symptomatic relief in a significant proportion of such patients, and long-term survival is possible in some patients.

Antineoplastic Combined Chemotherapy Protocols↗

Diffusion-weighted echo-planar MR imaging of CNS involvement in systemic lupus erythematosus.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the range of findings at diffusion-weighted magnetic resonance (MR) imaging in patients with systemic lupus erythematosus (SLE) and central nervous system involvement. MATERIALS AND METHODS: Diffusion-weighted MR images were reviewed in 20 patients with SLE and correlated with clinical symptoms and findings at computed tomography, conventional MR imaging, MR angiography, or conventional angiography. RESULTS: Diffusion-weighted MR imaging showed acute or subacute lesions in nine of 20 patients (45%). In the other 11, it showed no abnormal findings or chronic lesions. In four of the nine patients with lesions, diffusion-weighted imaging primarily showed hyperintense lesions with decreased apparent diffusion coefficient (ADC), which indicates acute or subacute infarcts. In four other patients, it primarily showed iso- or slightly hyperintense lesions with increased ADC, suggesting vasogenic edema. In two of these four patients, the findings were consistent with hypertensive encephalopathy. In the other two, small hyperintense foci on diffusion-weighted images with decreased ADC were seen within the vasogenic edema. These foci presumably represent microinfarcts associated with SLE vasculopathy. In the ninth patient, diffusion-weighted imaging showed a small linear hyperintense lesion with normal ADC in the left parietooccipital region. CONCLUSION: Diffusion-weighted imaging shows primarily two patterns of acute or subacute parenchymal lesions in patients with SLE: acute or subacute infarction and vasogenic edema with or without microinfarcts.

Adult↗

RECK gene expression in hepatocellular carcinoma: correlation with invasion-related clinicopathological factors and its clinical significance. Reverse-inducing--cysteine-rich protein with Kazal motifs.

The RECK (reversion-inducing-cysteine-rich protein with Kazal motifs) gene was initially isolated as a transformation suppressor gene. It encodes a membrane-anchored glycoprotein with multiple serine protease inhibitor-like domains. The RECK gene is expressed widely in normal organs but is undetectable in many tumor-derived cell lines. When artificially expressed in such cell lines, RECK suppresses their invasive and metastatic activities. Clinical implications of these findings, however, remained undefined because of the lack of studies using fresh human tumor samples. In the present study, we have addressed this issue by analyzing the levels of RECK gene expression in hepatocellular carcinoma (HCC). RECK mRNA was detectable by RNA blot hybridization in all the tumorous and contiguous nontumorous tissues obtained from 64 patients with HCC. In 26 cases, the RECK expression in tumorous tissues was higher than that in nontumorous tissues. The expression of RECK protein in these tissues could also be demonstrated by immunohistochemistry. Patients with high RECK mRNA expression in tumorous tissues tended to show better survival (P =.02), and such tumors had a tendency to be less invasive. Univariate and multivariate analysis revealed that the RECK mRNA expression is a novel and independent variable affecting overall survival (P =.01). These findings support the hypothesis that RECK has negative effects on the invasiveness of HCC cells and suggest the feasibility of RECK mRNA as a promising prognostic molecular marker for HCC.

Adult↗

Nonselective endothelin receptor antagonist initiated soon after the onset of myocardial infarction may deteriorate 24-hour survival.

To investigate the effects of endothelin blockade initiated immediately after the onset of myocardial infarction on survival and left ventricular remodeling, treatment with the nonselective receptor antagonist TAK-044 (n = 22) or saline (n = 19) for 3 weeks was initiated immediately after coronary ligation in rats. The 24-h survival rate was significantly lower in the TAK-044 group than in the saline group. The systolic blood pressure 24 h after the onset of myocardial infarction was similar in the saline and TAK-044 groups, although it was significantly lower in the TAK-044 group during the 3-week protocol. Heart weight/tibial length was significantly increased in the TAK-044 group compared with the saline group. As all deaths in the TAK-044 group occurred within 24 h after myocardial infarction, we performed additional experiments using a separate group of rats 12-16 h after myocardial infarction. Plasma and myocardial endothelin-1 levels were significantly increased, and a bolus injection of TAK-044 significantly reduced left ventricular dP/dtmax in these rats that had had a myocardial infarction compared with sham-operated rats. Endothelin receptor blockade initiated immediately after the onset of myocardial infarction may deteriorate acute-phase survival and left ventricular remodeling. Inhibition of the positive inotropic action of endothlin-1 may partially explain the increased 24-h mortality.

Animals↗

[Analysis of inquiries about prescriptions at the pharmacy of Gifu Pharmaceutical University].

The Ministry of Health, Labour and Welfare explains the objectives of promotion of separation of the pharmacy and clinics as the elimination of duplicated prescription of similar drugs and drug interactions caused by treatment at several departments or hospitals, and sufficient guidance in the use of drugs by pharmacists. The Pharmacy of Gifu Pharmaceutical University has dispensed prescriptions by outside medical organizations as its routine activity. In this study, the contents of question inquiries handled in routine activities were compiled and analyzed, and their meaning was evaluated. The contents of question inquiries were accumulated using data cards. The data obtained during 2 and a half years (562 cases) were analyzed. The percentage of the number of inquiries relative to the number of prescriptions was highest at 1.86% during the first 3 months and was 1.05-1.71% per 3 months thereafter. The inquiries were most frequently about "the dosage/regimen" (153 cases), followed by "discrepancy between the contents of prescription and understanding of the patient" (88 cases) and "problems about insurance coverage" (80 cases). There were also 16 inquiries about "the possibility of contraindications and adverse reactions" and 15 inquiries about "duplicated prescription", which may have exerted serious effects on the patients. Eighty nine % of the inquiries have led to changes in the prescriptions, and about half of these cases were discovered by consultation with the patients or a review of the drug history. Proper and positive execution of these operations in routine pharmacy work is considered to lead to appropriate inquiries about problems with prescriptions and, thus, contribute to the proper use of drugs and prevention of malpractice.

Drug Administration Schedule↗

[Simple method of stereotactic radiotherapy without stereotactic body frame for extracranial tumors].

Thirty-five patients with metastatic lung cancer(46 lesions) and twenty patients with primary lung cancer (21 lesions) have been treated with a simple method of stereotactic radiotherapy (SRT) without stereotactic body frame. Tumor size ranged from 1-4 cm in diameter. We used Vac-Lok cushion(Med-Tek) as a immobilization system. To be sure to include the respiratory movement of tumor to planning target volume(PTV), every patients were examined by fluoroscopy and radio-opaque catheters with the same length of tumor movement were attached on the anterior and lateral chest wall before CT simulation. A gold grain was implanted into a tumor that was invisible on fluoroscopy, as a radiomaker. Protocol of 60 Gy/8 fractions/2 weeks and 45 Gy/3 fractions/3-6 days were mainly used. The median follow-up period was 15 months for primary lung cancer and 19 months for metastatic lung cancer. Local control rates were 91% for metastatic lung cancer, 89% for primary lung cancer and 85% for T1, 2N0M0 cases. All patients developed mild pneumonitis or fibrosis about 4.5 months after SRT just in the treatment volume. Only three patients was symptomatic.

Clinical Trials as Topic↗

[Nationwide sensitivity surveillance of various antibiotic activities against bacteria isolated from patients with severe infections].

The susceptibility of 3,058 bacterial strains isolated between January and March, 1997 from patients with severe infections in Japan to ciprofloxacin and other injectable antimicrobial agents was measured using broth microdilution method. Methicillin-resistant Staphylococcus aureus (MRSA) strains were generally sensitive to vancomycin, teicoplanin and arbekacin, and resistant to CPFX and other antibacterial agents. MIC90 of CPFX against Streptococcus pneumoniae, to which MIC of ampicillin was more than 4 micrograms/mL, was below 2 micrograms/mL. PRSP (Penicillin resistant S. pneumoniae), which was also resistant to cephalosporins and carbapenems, showed no cross-resistance to CPFX. The susceptibility of Gram-negative bacteria to CPFX was as high as that to carbapenems. Especially, MIC90 against Pseudomonas aeruginosa was 2 micrograms/mL. 3 strains of isolated 446 P. aeruginosa strains had blaIMP gene. CPFX and pazufloxacin demonstrated good susceptibility with 0.25 microgram/mL of MIC to 2 strains of these 3 strains. The susceptibility rate of the most common isolates from patients suffering from lower respiratory tract infections excluding MRSA to CPFX was more than 80% (indication: % strains < pneumonia break point).

Anti-Bacterial Agents↗

Tissue factor pathway inhibitor-2 suppresses the production of active matrix metalloproteinase-2 and is down-regulated in cells harboring activated ras oncogenes.

A human placenta cDNA expression library was screened for genes inducing flat reversion when transfected into a v-K-ras-transformed NIH3T3 cell line, DT. One such gene was found to encode a Kunitz-type serine protease inhibitor, tissue factor pathway inhibitor-2 (TFPI-2). While the TFPI-2 mRNA can be detected in normal human fibroblasts (MRC-5), it is down-regulated in MRC-5 cells expressing an activated H-ras oncogene and in the human fibrosarcoma cell line, HT1080. Restored expression of the TFPI-2 gene in HT1080 cells resulted in the suppression of matrix invasion activity in vitro with concomitant decrease in the relative amount of active matrix metalloproteinase-2 secreted from the cells. When DT cells were cultured in the presence of conditioned medium and extracellular matrix prepared from TFPI-2-transfected HT1080 cells, increased attachment and flat reversion were observed. These results suggest that TFPI-2 may be required for the maintenance of the integrity of extracellular matrix in normal tissues and its down-regulation as a result of oncogene activation may contribute to the malignant phenotypes of tumor cells.

Animals↗