Experimental search for a 17-keV neutrino in the internal bremsstrahlung spectrum of 71Ge.
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Biomedical subjects
Publications and source records attributed to T Horiguchi.
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A monoclonal antibody (Th-10a) specific for the nuclear protein appearing in the S phase of the cell cycle in normal mouse thymocytes was derived by immunizing Wistar rats with a murine thymic lymphoma (TIGN), and its isotype was rat IgG2a and had kappa light chain. Immunohistochemical staining of frozen sections of B10.Thy1.1 newborn thymus and embryonic intestine revealed that this monoclonal antibody reacted strongly with the nuclear proteins of subcortical thymocytes and the basal layer of the mucosa, where many cells were dividing, but not with that of the thymic medullary area. To evaluate the expression of the nuclear proteins during the cell cycle in detail, the results of an immunofluorescence analysis of the thymocytes from hydroxyurea-treated B10 mice using Th-10a monoclonal antibody were compared with those of DNA synthesis of these cells with the use of the FITC-conjugated anti-BrdUrd monoclonal antibody. The results indicated that the nuclear protein detected by Th-10a monoclonal antibody was highly expressed in the S phase of normal thymocytes, while the cells in G1, G2 and M phases exhibited a low level of the expression. Moreover, the variations in expression of the nuclear proteins in the thymocytes at different times after hydroxyurea treatment were observed to correspond with the frequency of DNA synthesizing cells. In contrast, the high level and unregulated expression of the nuclear protein detected by Th-10a monoclonal antibody was observed throughout the cell cycle of the mouse lymphoma cell lines examined. Since Th-10a monoclonal antibody does not react with the nuclear proteins derived from human, hamster or rat proliferating cells, this antibody may recognize a murine specific epitope of the nuclear protein. To further characterize the nuclear proteins, we extracted them from normal thymocytes or thymic lymphomas, and analysed them by immunoblotting or immunoprecipitation followed by SDS-polyacrylamide gel electrophoresis. The nuclear protein(s) detected by Th-10a monoclonal antibody was mostly 95 kDa and also 83 kDa polypeptide. The results also indicated that the 95 kDa nuclear protein was phosphorylated in vivo.
The effect of vitamin E on the modulation of keratinocytes was studied in rats. A 1% lauroylsarcosine (LS) ointment caused skin erythema with keratinocyte-damage. A 30% vitamin E ointment markedly alleviated this erythema and protected keratinocytes from cell damage. Vitamin E (100 micrograms/ml) was also effective on LS (7.5 micrograms/ml)-induced proliferative reduction of cultured keratinocytes. On the other hand, ointment containing superoxide dismutase (SOD) (99,000 U/g) decreased the LS-induced erythema, suggesting that superoxide anion (O2-) produced from keratinocytes play an important role in the skin irritation. Indeed, LS induced O2- production from cultured keratinocytes. The O2- was significantly reduced by vitamin E and SOD, although vitamin E had no effects on O2- production in a xanthine-xanthine oxidase system, unlike the effect observed with SOD. These results indicate that vitamin E is an inhibitor of keratinocyte-modulation.
The microbial lipopeptides, TAN-1511 A, B and C, were isolated from the culture broth of Streptosporangium amethystogenes subsp. fukuiense AL-23456. Their structures were elucidated on the basis of their reactions and spectroscopic analyses. These lipopeptides were mixtures of molecules having different lengths of fatty acids. The metabolites stimulated the proliferation of bone marrow cells from BALB/c female mice at very low concentrations (concentration giving 30% increase: A and B, 0.313 ng/ml; C, 1.25 ng/ml). We confirmed that chemically synthesized TAN-1511 A analogue [(2R,6R)-2-tetradecanoylamino-6,7- bis(hexadecanoyloxy)-4-thiaheptanoyl-Gly-Gly-Gly-Glu-Thr-Thr -OH] stimulated the proliferation of bone marrow cells in a manner similar to that of natural TAN-1511 A. This analogue induced the secretion of both granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF), and potentiated the generation of Gr-1 positive cells in the bone marrow cell culture. Moreover, it effected the G-CSF mediated restoration of granulocytopoiesis in a murine leukopenia model.
A 56-year-old male who had been followed for chronic hepatitis had cough and hemosputum. Chest X-ray and CT films showed an abnormal mass shadow in the right thorax. On suspicion of intrathoracic tumor, resection was performed. The tumor, which was on the diaphragm without invasion, was pedunculated and arose from the bottom surface of visceral pleura of the right lower lobe. From the microscopic findings and immunohistochemical staining, the tumor was diagnosed as localized fibrous mesothelioma. Some localized fibrous mesothelioma exhibit as malignant tumor. Therefore, complete resection and intensive follow-up should be done.
The efficacy and safety of video thoracoscopic lung biopsy (VTLB) and of open lung biopsy (OLB) were compared in patients with diffuse lung diseases. Thirty-three patients who had undergone VTLB were retrospectively studied and compared with 67 patients who had undergone OLB. There were no significant differences in age (52.8 +/- 10.9 vs 53.4 +/- 10.3), in the number of biopsies per patient (2.6 +/- 0.6 vs 2.7 +/- 0.6), or in the rate of diagnosis (94% vs 93%) between the two groups. However, the rate of diagnosis was low when the number of VTLB or OLB performed per patient was low. The patients undergoing VTLB had significantly shorter operative times (VTLB, 100.2 +/- 27.2 min. vs OLB, 119.8 +/- 42.6 min; p < 0.01) and less blood loss (VTLB, 4.7 +/- 14.6 ml vs OLB, 65.7 +/- 77.0 ml; p < 0.001). Complications occurred in 3 of the 33 who underwent VTLB, and in 18 of the 67 who underwent OLB. These results indicate that VTLB is an effective and safe alternative in the diagnosis of diffuse lung diseases.
The p80cdc25 protein is a protein phosphatase directly involved in p34cdc2 protein kinase activation by dephosphorylation. The cdc25B gene is one of three human cdc25 homologs which can complement the temperature-sensitive cdc25 mutation of Schizosaccharomyces pombe, and is expressed a high levels in human cell lines, particularly in some cancer cells. A fusion protein of glutathione-S-transferase (GST) and the catalytic domain of cdc25B protein was constructed and found to retain phosphatase activity in the manner of a p80cdc25 phosphatase by using a chromogenic substrate, p-nitrophenylphosphate. Two benzoquinoid antitumor compounds, dnacin A1 and dnacin B1, inhibited phosphatase activity in a non-competitive manner.
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The complete nucleotide sequence of the multicopy, self-transmissible, broad-host-range Streptomyces plasmid pSN22, originating from Streptomyces nigrifaciens, was determined. pSN22 is a circular DNA molecule, 10,922 bp with 71.76% G + C. Computer-assisted analysis identified 10 open reading frames (ORFs); 8 of them--traA (155 amino acids [aa], traB (651 aa), traR (246 aa), spdB1 (107 aa), spdB2 (251 aa), spdB3 (70 aa), spdB4 (128 aa) and spdA (154 aa)--are involved in plasmid transfer and pock-formation. One ORF, rep (451 aa), probably encodes a replication protein similar to known replication proteins of rolling circle replicons. The four spdB genes have hydrophobic amino termini that might attach to the cytoplasmic membrane. The deduced rep proteins of pSN22 and pIJ101 are very similar, suggesting that both are derived from a recent common ancestor. The transfer regions of the two plasmids are, however, very different. The only detectable similarities between presumably analogous proteins are DNA- and NTP-binding motifs and hydrophobic regions. This suggests that two transfer regions are of separate origins.
The replication of the 11 kb conjugative multicopy Streptomyces plasmid pSN22 was analyzed. Mutation and complementation analyses indicated that the minimal region essential for plasmid replication was located on a 1.9 kb fragment of pSN22, containing a transacting element encoding a replication protein and a cis-acting sequence acting as a replication origin. Southern hybridization showed that minimal replicon plasmids accumulated much more single-stranded plasmid molecules than did wild-type pSN22. Only one strand was accumulated. A 500 bp fragment from the pSN22 transfer region was identified which reduced the relative amount of single-stranded DNA, when added in the native orientation to minimal replicon plasmids. This 500 bp DNA sequence may be an origin for second-strand synthesis. It had no effect on the efficiency of co-transformation, plasmid incompatibility, or stability. The results indicate that pSN22 replicates via single-stranded intermediates by a rolling circle mechanism.
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Fungal metabolites with an epi-oligothiadiketopiperazine structure, TAN-1496 A, C and E, were isolated from the culture broth of Microsphaeropsis sp. FL-16144. Their molecular formulas were determined to be C22H28N2O9S2, C22H28N2O9S3 and C22H28N2O9S4, respectively. Structures were determined by comparing the NMR data with those of known diketopiperazine antibiotics, sirodesmins. These metabolites inhibited the relaxation of supercoiled pBR322 DNA by calf thymus topoisomerase I but did not affect the decatenation of kinetoplast DNA by calf thymus topoisomerase II at concentration up to 500 microM. They strongly suppressed the growth of various murine and human tumor cells and induced apoptosis. Moreover, various derivatives were synthesized to investigate the relationship of their functional groups and biological activities.
New naphthacenecarboxamide antibiotics, TAN-1518 A and B, were isolated from a culture broth of Streptomyces sp. AL-16012. Their structures were elucidated from their reactions and from spectroscopic analyses. The relaxation of supercoiled pBR322 DNA by calf thymus DNA topoisomerase I was inhibited by these metabolites as potently as by camptothecin. However, the decatenation of kinetoplast DNA by calf thymus DNA topoisomerase II was little affected by these agents. The major metabolite, TAN-1518 A, strongly suppressed the growth of various murine and human tumor cells, inducing apoptosis. Unlike camptothecin, TAN-1518 A did not stimulate cleavable complex formation in the nuclei of CHO-K1 cells and had weak activity in intercalating into DNA strands. This metabolite arrested the growth of human tumor cell lines in G1 phase of the cell cycle. These results suggest that TAN-1518 A and B are novel antitumor agents targeting topoisomerase I.
A 23-year-old man was admitted to our hospital because of non-productive cough. Chest X-ray demonstrated bilateral hilar lymphadenopathy, bilateral infiltration shadows and right pleural effusion. ECG showed complete A-V block and sinus arrest. Transbronchial lung biopsy and pleural biopsy specimens showed non-necrotizing epithelioid cell granulomas. The patient was diagnosed as having sarcoidosis, and was treated with steroid and pacemaker. After steroid therapy, myocardial imaging with thallium-201 showed increase of uptake and the pleural effusion disappeared.
We report the first case of respiratory bronchiolitis-associated interstitial lung disease in Japan. A 48-year-old man with a 36-pack-year smoking history was referred because of 6 months of dry cough. Chest X-ray showed bilateral reticulonodular shadows. HRCT scan showed bilateral reticulonodular and ground glass shadows with centrilobular distribution. BAL yielded 85 x 10(6) cells with 99.5% macrophages. Histologic examination of the biopsy specimen obtained under thoracoscopy showed evidence of respiratory bronchiolitis, with accumulation of pigmented macrophages within respiratory bronchioles and adjacent air spaces associated with mild thickening of the peribronchiolar interstitium.
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BACKGROUND: Small cell lung cancer (SCLC) is highly sensitive to chemotherapy. Despite the introduction of intensive combination chemotherapy, long-term disease-free survivors are still rare. The emergence of drug-resistant tumor cells during chemotherapy is presumed to be the major cause of poor outcome. METHODS: A pilot Phase II study of hybrid chemotherapy for patients with SCLC was conducted between October 1986 and March 1988. Dose and schedule for each drug in the regimen were as follows: cyclophosphamide, 700 mg/m2 intravenously (IV), day 1; doxorubicin, 30 mg/m2 IV, day 1; vincristine, 1.4 mg/m2 IV, day 1; cisplatin, 60 mg/m2 IV, day 8; and etoposide, 100 mg/m2 IV, days 8 and 9. Courses were repeated every 4 weeks for up to six cycles. Patients with limited disease (LD) received chest irradiation of 5000 cGy when a maximal response was achieved. Only patients with LD who achieved a complete response (CR) received prophylactic cranial irradiation of 3000 cGy. RESULTS: Thirty-six patients were enrolled and fully evaluated for tumor response and toxicity. All 20 patients with LD responded to the regimen, and 14 (70%) of those achieved a CR. Of 16 patients with extensive disease (ED), 7 CR and 7 partial responses were noted, indicating an overall response rate of 88%. The median survival time was 23.6 months for patients with LD and 12.6 months for those with ED. Myelosuppression was the major toxicity, but it was generally well tolerated. CONCLUSIONS: These results indicate that the hybrid regimen is a highly active one for the treatment of patients with SCLC and warrants additional clinical trials.