Biomedical subjects
Publications and source records attributed to S Takamatsu.
A benzoyl group was introduced onto the 3'-hydroxyl group of 6-chloropurine riboside by treatment with benzoic anhydride in the presence of a base in aqueous solution. The product (3b) was converted to 9-(2,3-Di-deoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (1, FddA) in 6 steps, including radical deoxygenation.
Structural analysis of the sugar chains of human chorionic gonadotropin (hCG) has revealed that abnormal biantennary structures appear specifically on hCG in the urine of choriocarcinoma patients. However, the enzymatic and molecular mechanisms of the biosynthesis of abnormal biantennary sugar chains have not yet been elucidated. In this report, the enzyme activities and the expression levels of mRNAs of N-acetylglucosaminyltransferases (GnT)-I to -V, beta-1,4-galactosyltransferase, and alpha-mannosidase II in normal human placentae and three human choriocarcinoma cell lines were investigated. GnT-IV activities in choriocarcinoma cell lines were increased from 16- to 66-fold and GnT-III activity was increased from 15- to 25-fold as compared with those in human placentae, whereas other enzyme activities were not increased significantly. The mRNA expression levels generally correlated with their enzyme activities. Among the two GnT-IV genes found in human tissues only GnT-IVa gene was strongly expressed in the cancer cells: from three to seven times as much as in the normal tissue, whereas that of GnT-IVb remained constant. On the basis of these results, we proposed that ectopic expression of GnT-IVa gene should occur along with the malignancy of trophoblastic tissues, and that the increased GnT-IV activity should be the main cause of the formation of abnormal biantennary sugar chains in choriocarcinoma. A possible enzymatic basis of the biosynthesis of abnormal biantennary sugar chains is discussed.
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A human cDNA for UDP- N -acetylglucosamine:alpha1,3-d-mannoside beta1,4- N- acetylglucosaminyltransferase (GnT-IV) was isolated from a liver cDNA library using a probe based on a partial cDNA sequence of the bovine GnT-IV. The cDNA encoded a complete sequence of a type II membrane protein of 535 amino acids which is 96% identical to the bovine GnT-IV. Transient expression of the human cDNA in COS7 cells increased total cellular GnT-IV activity 25-fold, demonstrating that this cDNA encodes a functional human GnT-IV. Northern blot analysis of normal tissues indicated that at least five different sizes of mRNA (9.7, 7.6, 5.1, 3.8, and 2.4 kb) forGnT-IV are expressed in vivo. Furthermore, these mRNAs are expressed at different levels between tissues. Large amounts of mRNA were detected in tissues harboring T lineage cells. Also, the promyelocytic leukemia cell line HL-60 and the lymphoblastic leukemia cell line MOLT-4 revealed abundant mRNA. Lastly, the gene was mapped at the locus on human chromosome 2, band q12 by fluorescent in situ hybridization.
Diagnosis of cervical lymph nodes from head and neck tumors was studied using MRI turbo-STIR (short TI inversion recovery) sequence and conventional MRI sequence in 15 patients. After the MRI examination, 10 of the 15 patients underwent radical neck dissections. The detection of cervical lymph nodes with the conventional MRI was not clear. However, MRI turbo-STIR depicted clear cervical lymph node margins by selectively suppressing fat signals. Thus, the accuracy of diagnosis of cervical lymph nodes by the turbo-STIR was higher than by conventional MRI. On the other hand, differential diagnosis between metastatic and non-metastatic lymph nodes remains difficult only by turbo-STIR. These findings suggest that MRI turbo-STIR sequence is more useful in the detection of cervical lymph nodes than the conventional MRI methods.
We often experience hepatic metastases after resections for advanced gastrointestinal cancers. Various methods such as resection and hepatic arterial infusion chemotherapy are used when a metastatic tumor is detected on imagings. We have considered postoperative prophylactic hepatic arterial infusion chemotherapy for the prevention of heterochronous hepatic metastases. For this purpose, we conducted experimental trials of temporary insertion of a catheter, which we would be able to remove safely in the near future, into an artery. Laparotomy was done on rabbits under general anesthesia, and a 16 G catheter was inserted into the left renal artery. The proximal site of the artery and the catheter were ligated together with Elastik, and the catheter was fixed with coated VICRYL RAPIDE distal of the insertion point. Upon insertion of the catheters, there was no bleeding, and neither occlusion nor dislocation of the catheter occurred. Two weeks later, the catheters were easily removed without bleeding under laparotomy. At a second-look laparotomy after 2 more weeks, there were no abnormal findings such as hematomas. Therefore, we concluded that our method would be acceptable for the temporary catheter insertion into an artery which could be removed safely and easily when the chemotherapy was finished.
OBJECTIVE: The aim of this study was to examine the role of histamine in regulation of IL-6 and M-CSF gene expression in bone marrow stromal cells. Total cellular synthesis was also estimated for IL-6. MATERIALS: The effects of the amine were evaluated using the stromal cell line, MC3T3-G2/PA6 (PA6). RESULTS: Histamine caused a distinct accumulation of IL-6 mRNA in the cells, whereas it decreased M-CSF transcripts. Both pyridylethylamine, a H1 agonist, and dimaprit, a H2 agonist, caused a large increase in the level of IL-6 mRNA in PA6 cells. The histamine-induced expression of IL-6 mRNA was associated with enhanced secretion of IL-6, as determined by ELISA. CONCLUSIONS: These results, together with the results of our previous studies, suggest that histamine produced by stromal macrophages differentially regulates the production of IL-6 and M-CSF in other kinds of stromal cells and hence promotes differentiation and/or proliferation of hematopoietic progenitor cells.
We isolated a novel cDNA encoding a second isoenzyme of UDP-N-acetylglucosamine:alpha1,3-D-mannoside beta1,4-N-acetylglucosaminyltransferase (GnT-IV; EC 2.4.1.145). The nucleotide and deduced amino acid sequences of the cDNA were homologous to those of the previously cloned human GnT-IV cDNA (63% and 62% identity, respectively). The new cDNA is also confirmed to express GnT-IV activity, suggesting that two isoenzymes of human GnT-IV exist. Although genomic Southern analysis suggested that both genes exist in many mammalian species and the chicken, northern analysis revealed that both genes are expressed in different ways in human tissues. This is the first report concerning the gene family of an N-acetylglucosaminyltransferase in mammals.
To evaluate the diagnostic utility of blood biochemical parameters in assessing degree of hepatic fibrosis, serum levels of aminoterminal type III procollagen peptide (P III P), type IV collagen (IV-collagen), 7S domain of type IV collagen (7S-collagen), and hyaluronan (HA) were measured in 54 patients with chronic viral liver disease. Liver collagen content was quantified by a computer-assisted image analysis method. Significant correlations were found between the amount of collagen in the liver and serum levels of P III P (r = 0.482; P < 0.02), IV-collagen (r = 0.705; P < 0.001), 7S-collagen (r = 0.771; P < 0.001), and HA (r = 0.595; P < 0.001). To optimize diagnostic efficacy, we applied multivariate regression analysis to the combined results obtained for these blood biochemical parameters and some additional laboratory tests. The correlation coefficient obtained from the application of this model was 0.809. To measure the predictive value of the proposed model, we used it to estimate collagen content in an additional 16 patients with chronic liver disease and compared the estimated to the actual amount of collagen determined by direct measurement. The correlation coefficient was 0.937. These results suggest that application of the model would be useful for the assessment of collagen content of fibrotic liver.
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A new melanogenesis inhibitor, named amphistin, was isolated from the fermentation broth of an actinomycete strain KP-3052. Amphistin was purified from the culture filtrate by the combination of cation exchange, gel filtration, and aminosilyl silica gel chromatographic methods. The structure of amphistin was elucidated as gamma-(beta-histidinoalanino)homoalanine by NMR experiments including 1H-15N HMBC experiment and other spectroscopic analyses. Amphistin inhibited the melanogenesis of B16 melanoma cells at concentration of 6.8 microM.
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Two new alkaloids with the beta-carboline skeleton, pyridindolols K1 (C18H18N2O5) and K2 (C16H16N2O4), were isolated from the culture both of Streptomyces sp. K93-0711. The structure of pyridindolols were established by spectroscopic investigations and chemical transformations. Pyridindolol K2 inhibited the adhesion of HL-60 cells to LPS-activated HUVEC monolayer (IC50 = 75 micrograms/ml).
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A 28-year-old female underwent sigmoidectomy for sigmoid colon cancer with peritoneal seeding. One month later, a solitary metastasis was found in S3 of the liver. After CDDP/5-FU intravenous chemotherapy, another metastasis appeared in S7. Intravenous administration showed PD. But the metastatic tumors shrank and became inobservable by CT after the 1st round of CDDP/5-FU intraperitoneal chemotherapy, and S7 tumor could not be identified after the 2nd round. Many previous reports demonstrated the concentration of cytotoxic drug in intraperitoneal administration was much higher than in intravenous administration. Theoretically, intraperitoneal chemotherapy is superior to intravenous chemotherapy for the prevention and treatment of liver metastases. This case demonstrated this hypothesis was right. We think adjuvant intraperitoneal chemotherapy should be re-considered for the prevention of the liver metastases of gastrointestinal cancers.
Sequential MTX/5-FU therapy (intravenous route) is powerful chemotherapy especially for poorly differentiated adenocarcinoma of the stomach and its peritoneal metastases. The authors had proposed the idea of intraperitoneal sequential MTX/5-FU chemotherapy for potential peritoneal metastases and micrometastases from advanced gastric carcinoma. This experimental study was planned to confirm this experimentally. Peritoneal seeding model of nude mice was made by the intraperitoneal inoculation of human gastric cancer cell line MKN-45. Control group (n = 5) had no treatment. The intraperitoneal (i.p.) group and intravenous (i.v.) group underwent the treatments on the 7th, 14th, and 21st day after cell implantation. Experimental chemotherapies consisted of intraperitoneal injection of MTX (15 mg/kg, 1.5 ml saline) and 5-FU (50 mg/kg, 1.0 ml saline) for i.p. group and intravenous injection of MTX (15 mg/kg, 0.2 ml saline) and 5-FU (50 mg/kg, 0.2 ml saline) for i.v. group. Interval time between MTX and 5-FU administration was 2 hours. On the 35th day after the cell implantation necropsies were performed. Counting of peritoneal metastatic nodules revealed the number of nodules of control group. (14.2 +/- 6.7) > i.v. group (5.3 +/- 4.1) > i.p. group (0.41 +/- 0.7) (p < 0.05). Weight of omental tumors showed Control group (0.246 +/- 0.136 g) > i.v. group (0.140 +/- 0.068 g) > i.p. group (0.051 +/- 0.017 g) (i.v.-i.p., p < 0.01). The mouse body weight decrease less in the i.p. group than in the i.v. group (p < 0.05) throughout this experiment. The results of this experiment demonstrated intraperitoneal sequential MTX/5-FU therapy was more effective than intravenous sequential MTX/5-FU therapy for potential peritoneal seeding and peritoneal micrometastases from the gastric cancer. Moreover, the side effect of intraperitoneal administration was milder than by the intravenous route.
Two new alkaloids with the beta-carboline skeleton, pyridindolols K1 (C18H18N2O5) and K2 (C16H16N2O4), were isolated from the culture broth of Streptomyces sp. K93-0711. The structure of pyridindolols were established by spectroscopic investigations and chemical transformations. Pyridindolol K2 inhibited the adhesion of HL-60 cells to LPS-activated HUVEC monolayer (IC50 = 75 micrograms/ml).