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Biomedical subjects

K Miwa

Publications and source records attributed to K Miwa.

At least 379 records · Page 21Linked to original sources

Sequence-specific interactions of nuclear factors with conserved sequences of human class II major histocompatibility complex genes.

All class II major histocompatibility complex genes contain two highly conserved sequences, termed X and Y, within the promoter regions(s), which may have a role in regulation of expression. To study trans-acting factors that interact with these sequences, sequence-specific DNA binding activity has been examined by the gel electrophoresis retardation assay using the HLA-DQ2 beta gene 5' flanking DNA and nuclear extracts derived from various cell types. Several specific protein-binding activities were found using a 45-base-pair (bp) HinfI/Sau96I (-142 to -98 bp) and a 38-bp Sau96I/Sau96I (-97 to -60 bp) fragment, which include conserved sequence X (-113 to -100 bp) and conserved sequence Y (-80 to -71 bp), respectively. Competition experiments, methylation interference analysis, and DNase I foot-printing demonstrated that distinct proteins in a nuclear extract of Raji cells (a human B lymphoma line) bind to sequence X, to sequence Y, and to DNA 5' of the X sequence (termed sequence W). The factor binding site in the W sequence is also found to be conserved among beta-chain genes and is suggested to be a gamma-interferon control region.

B-Lymphocytes↗

Two single-base-pair substitutions causing desensitization to tryptophan feedback inhibition of anthranilate synthase and enhanced expression of tryptophan genes of Brevibacterium lactofermentum.

A 5-fluorotryptophan-resistant mutant, termed 1041, was isolated from Brevibacterium lactofermentum AJ12036. The anthranilate synthase of 1041 was insensitive to feedback inhibition by tryptophan, and the specific activities of the anthranilate synthase and anthranilate phosphoribosyltransferase of 1041 were 29- and 23-fold higher than those in parental strain AJ12036, respectively. A single-base change (adenine to cytosine) that resulted in a Ser-to-Arg substitution was found in the trpE structural gene of 1041. This substitution was identified as the cause of the desensitization to feedback inhibition by tryptophan of anthranilate synthase in 1041. Another substitution (guanine to adenine) was found at a position in which a mutation would destabilize the rho-independent terminator structure within the putative attenuator. The enhanced synthesis of tryptophan enzymes in 1041 could be caused by this substitution in the attenuator.

Amino Acid Sequence↗

[Malignancy of gastric cancer according to DNA ploidy pattern and tumor markers].

Microfluorometric analysis of DNA content was performed on samples from 172 gastrectomy specimens of cancer. Histograms of DNA content were classified into three ploidy patterns; type I, II and III. Also, immunocytochemical examination for tumor markers (CEA, AFP and hCG) was performed. Type I was predominant in intramucosal carcinoma. Type III was predominant in differentiated carcinomas, in elevated type of early carcinomas and in gross type 1 and 2 of advanced carcinomas. Prognostic serosal factor exerted a greater influence on the prognosis than ploidy pattern. But in the patient without prognostic serosal factor, type III had a poorer prognosis than the other types because of vessel invasion, lymph node metastasis and liver metastasis. AFP and hCG were highly positive in type III. Furthermore type III cancer producing more than two tumor markers had an extremely poor prognosis. Analysis of ploidy pattern and tumor markers may prove to be a highly useful adjunct in the evaluation of malignancy in gastric cancer.

Biomarkers, Tumor↗

[A case of gastric cancer with marked response to intra-arterial infusion of cisplatinum, mitomycin C and 5-fluorouracil].

The prognosis for patients with unresectable gastric cancer is so poor that 50% survival time is no more than 3 months. A 58-year-old woman was admitted for advanced gastric cancer with multiple liver metastases. Preoperatively, she received hepatic arterial infusion of 75 mg/m2 of cis-platinum during abdominal angiography. As laparotomy revealed an unresectable gastric tumor of the classification H3P2N4S3, a catheter was introduced into the aorta at the level of the celiac axis via a branch of the right femoral artery and 10 mg of Mitomycin C was infused into the abdominal aorta through the catheter. Postoperative chemotherapy consisted of continuous intra-arterial infusion of 250 mg/day of 5-Fluorouracil for 14 days, followed by infusion of another 10 mg of Mitomycin C. Daily oral administration of 600 mg of tegafur was continued in the outpatient clinic. Three months after surgery, the primary and hepatic metastatic lesions had regressed by 76 and 88-98% on abdominal computed tomography and gastric fluoroscopy, respectively. The dimensions of the lesions remained unchanged for the subsequent two months, and their responses to the treatment were judged PR. Eight months after surgery, the patient is in good general condition.

Antineoplastic Combined Chemotherapy Protocols↗

[Multimodal therapy using hyperthermia for gastric cancer--with special reference to histological studies].

We carried out a combination preoperative therapy involving radiofrequency hyperthermia (8 MHz or 13.56 MHz) with radiation (10-MV X-ray) or chemotherapy (Mitomycin C, CDDP or UFT) for 24 advanced gastric cancers with the aim of preventing local recurrence and improving resectability. The tumor and histological effects were evaluated in each case. Furthermore, an agar phantom possessing a cavity, for simulating the stomach, was employed in an experiment to evaluate temperature distribution upon RF-heating. In the experiment using the agar phantom, the rising temperature around the cavity at 3 o'clock was higher than at 5' and 6 o'clock. This suggested that gastric juice and air must be aspirated when treating a patient by RF-heating. Of the 24 tumors, 4 (17%) showed partial response. Histological effects were observed in 67% of 21 primary tumors. The rate of histological effects in metastases of lymph nodes, liver and peritoneum were 29% (4/14), 100% (2/2) and 0% (0/4), respectively. Tumor response was closely correlated with irradiation and the temperature in the stomach cavity (over 42.5 degrees C). Almost all patients showed good tolerance of this combined therapy. These results show that combined treatment involving radiation, chemotherapy and hyperthermia appears to be a potentially useful from of preoperative therapy for patients with advanced gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[A long-surviving case of gastric cancer with liver metastasis without signs of recurrence for six years after palliative operation].

A 51-year-old man was admitted because of Borrmann 2 type gastric cancer located in the antrum. Since he had bilateral liver metastasis, palliative gastrectomy and liver biopsy was performed. Histopathologically, the primary cancer showed poorly differentiated adenocarcinoma and the liver biopsy showed the same. This patient has been alive without sign of recurrence for more than six years after he was given 40 mg of MMC, 12.5 KE of Picibanil and 528 g of PSK postoperatively. In addition, eight similar cases, with a survival rate of more than 5 years after resection of liver metastasis, have been reported in Japan and are reviewed.

Adenocarcinoma↗

[Present status in the nationwide registration of gastric cancer].

The nationwide registration of gastric cancer was started in 1963 when about 6,000 cases were registered. Thereafter, the number of registered cases gradually increased and amounted to 200,000 in 1985. The frequency of detection of early gastric cancer among gastrectomized cases has steadily increased from 10% in 1963 to 30% in 1978. In particular, the increase in the incidence of early cancer with "m" depth is significant. The resection rate among all primary gastric cancer patients increased from 68% in 1963 to 83% in 1978, and the rate of total gastrectomy also increased from 14% to 23%. The operative direct death rate has decreased irrespective of the extent of gastrectomy. The relative 5-year survival rate of all primary cases was 29.8% in period [a] (1963-66), and 48.2% in period [C] (1974-78), with an increase in the rate of 18.4% over about 10 years. In the meantime, the rates of gastrectomized cases and those given macroscopic curative operation showed respective increases of 13.5% (from 44.3% to 57.8%) and 11.9% (from 60.8% to 72.7%). Improvement in the treatment results was more significant in advanced stage disease. The provisional TNM stage grouping was examined with the treatment results of 15,589 cases registered at member institutions of the Japanese Research Society For Gastric Cancer in period [B] (1969-73) and was shown to have marked irrationality. A more rational stage grouping was therefore devised and proposed and was wholly adopted by the UICC TNM Classification Committee in 1985.

Gastrectomy↗

Covalent binding of a mercaptan S-sulfate to hepatic cytosolic proteins and its inhibition by glutathione.

4-Nitrobenzyl mercaptan (NBM) S-sulfate, a new type of the sulfate conjugate enzymatically formed from NBM in the presence of 3'-phosphoadenosine 5'-phosphosulfate in rat liver cytosol, bound covalently to rat liver cytosolic proteins at pH 7.4. The protein binding of NBM S-sulfate was strongly retarded by GSH. GSH not only played a role as a scavenger for NBM S-sulfate with formation of NBM and GSSG via S-(4-nitrobenzyl)thioglutathione, but also cleaved the covalent bonds, possibly disulfides formed from NBM S-sulfate and sulfhydryl groups of the cytosolic proteins. Thus, evidence was provided that NBM S-sulfate be a new type of the reactive metabolite.

Animals↗

Granular cell tumor of the esophagus.

A case of granular cell tumor of the esophagus in a 50-year-old man is reported. Gastrointestinal endoscopy revealed a round, sessile, non-ulcerated white-yellow elevated tumor at the lower third of the esophagus. Biopsy revealed a granular cell tumor. Immunohistochemical staining demonstrated that granules in the cytoplasm of tumor cells were positive for S-100 protein and negative for carcinoembryonic antigen. An electron microscopic study revealed that tumor cells were closely packed in clusters, surrounded by basal lamina and collagen fibers. Most cells contained dark cytoplasm filled with electron-dense granules. These granules resembled lysosomes and phagosomes. In a few cells with clear cytoplasm, some mitochondria and poorly developed endoplasmic reticulums were seen. Fibrillar internal materials, myelin-like figures and a premature angulate body were observed in the clear cytoplasm. The lesion has remained unchanged in gross appearance and in size for twenty-three months without any treatment.

Biopsy↗

[Improvement of Japanese general rules and the TNM classification of stomach cancer--a proposal for a new stage-grouping].

At present, three major manuals for gastric cancer study are in use, the General rules of the Japanese Research Society (JRS), the TNM classification of the UICC, and the TNM classification of the American Joint Committee (AJC). Differences between these systems have produced considerable confusion and rendered comparison between different reports very difficult. In order to produce an internationally unified system of staging, a meeting was held in December 1984 in Hawaii between experts in gastric cancer representing the UICC, the AJC, and the JRS. A new TNM classification and staging was proposed at the meeting and was approved by the UICC, the AJC, and the JRS in 1985. In this paper, the background and evolution of the new classification are described, and end results of surgical treatment staged by this system are presented.

Humans↗

The S-sulfate formation from 4-nitrobenzyl mercaptan in rat liver cytosol.

4-Nitrobenzyl mercaptan (NBM) was enzymatically transformed at pH 6.0 into its S-sulfate in rat liver cytosol fortified with 3'-phosphoadenosine 5'-phosphosulfate. At pH 7.4, the S-sulfate was not detected from the incubation mixture. 4-Nitrobenzyl alcohol was also transformed under the same incubation conditions into the corresponding O-sulfate at a higher rate at pH 6.0 than at pH 7.4. Under the incubation conditions used, NBM S-sulfate reacted with the substrate NBM at a significant rate to afford 4-nitrobenzyl disulfide. The disulfide formation from NBM and the S-sulfate occurred more readily at pH 7.4 than at pH 6.0, so that biologically formed NBM S-sulfate was strongly suggested not to remain unchanged in the incubation mixture at pH 7.4.

Animals↗