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Biomedical subjects

T Fujimura

Publications and source records attributed to T Fujimura.

At least 73 records · Page 4Linked to original sources

[Blood kinetics of free-platinum in CDDP hepato-arterial injection therapy].

In CDDP hepato-arterial injection therapy, platinum (Pt) concentration in hepatic and peripheral venous blood were determined in two groups with different injection rates, and the blood kinetics of Pt was examined. Seven cases of digestive cancers having liver metastases were given CDDP (100 mg) selectively into the proper hepatic artery at a constant rate (10 or 40 min). After injection, concentration of non-protein-bound Pt in hepatic and peripheral venous blood were determined. Pt concentration and AUC value were higher in hepatic venous blood at injection rate than peripheral venous blood. On the other hand, Pt concentration in hepatic venous blood in the cases 10 min-injection were higher than those received 40 min-injection, but neither Pt concentration in peripheral venous blood nor incidences of the side effects and abnormal clinical findings were influenced by the injected rates.

Adult

Portable encapsidation signal of the L-A double-stranded RNA virus of S. cerevisiae.

The (+) single-stranded RNA (ssRNA) of the L-A virus is the species packaged to form new viral particles. Empty L-A viral particles specifically bind viral (+) ssRNA, and a sequence 400 bases from the 3' end is necessary for this activity. We show that its stem-loop structure, the A residue protruding from the stem, and the loop sequence are all important for the binding, and that this 34 base region is sufficient for the binding. M1, a satellite virus of L-A, has a similar structure on its (+) strand that is likewise sufficient for the binding. Heterologous RNA with the binding sequence from L-A or M1, when expressed in vivo, was packaged in L-A viral particles. Thus, the sites necessary to bind to empty particles are encapsidation signals for the L-A virus. Since the pol domain of the 180 kd minor coat protein appears to be responsible for the binding, this result suggests that the RNA polymerase molecule recognizes the viral genome for packaging.

Base Sequence

Secretion of recombinant ribonuclease T1 into the periplasmic space of Escherichia coli with the aid of the signal peptide of alkaline phosphatase.

The ribonuclease T1 (RNase T1) gene was ligated to a synthetic gene for the signal peptide of Escherichia coli alkaline phosphatase. When this fusion gene was expressed in E. coli under the control of the trp promoter, active RNase T1 having the correct N-terminal sequence was secreted into the periplasmic space, indicating that the heterologous signal peptide had been cleaved off correctly. The enzyme could be readily purified from the periplasmic fraction with a yield of 1.8 mg from 1 liter culture. Adopting the same strategy, it was possible to produce a labile mutant of RNase T1 (Glu-58----Ala mutant) in E. coli, the yield of the purified mutant enzyme being 2.0 mg from 1 liter culture.

Alkaline Phosphatase

Continuous hyperthermic peritoneal perfusion for the treatment of peritoneal dissemination in gastric cancers and subsequent second-look operation.

A total of 31 patients with gastric cancer showing peritoneal dissemination received continuous hyperthermic peritoneal perfusion (CHPP) in combination with the administration of cisplatin (CDDP) and mitomycin C (MMC). The authors developed a new special device named the peritoneal cavity expander (PCE) for sufficient perfusion and direct temperature measurement in the peritoneal cavity. As complications of CHPP three patients presented with bone marrow suppressions (leukocytes less than or equal to 3000/mm3 and/or platelets less than or equal to 30,000/mm3): one, leakage of intestinal anastomosis; one, intestinal perforation; and one, acute renal failure. But none of them was lethal. Twelve of 31 patients who had received CHPP during the initial operation underwent second-look operation (SLO) for the assessing the effects of CHPP and for resecting residual or recurrent tumors. Among 12 patients who received SLO complete response (CR) was observed in four patients, partial response (PR) in one, no change (NC) in three, and progressive disease (PD) in four, with the overall response rates (%CR + %PR) standing at 41%. Two-year survival rate of the complete and partial responders was 50%, which was significantly higher than 0% of the other responders (NC + PD). The survival curves of the two groups were significantly different (P less than 0.05, generalized Wilcoxon test). These results supported that CHPP was well tolerated and effective for the treatment of patients with peritoneal dissemination in gastric cancer when combined with anti-cancer drugs having synergism with hyperthermia. Since the outcome of SLO was one of prognostic factors it was important to follow up these patients by SLO.

Adult

Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer.

To examine the clinical efficacy and the mechanism of action of polysaccharide K (PSK), a protein-bound polysaccharide extracted from a Basidiomycetes fungus, a randomized double-blind trial was performed by administering PSK to 56 patients and a placebo to another group of 55 patients after surgical operations on their colorectal cancers. The rate of patients in remission (or disease-free) was significantly higher in the PSK group than in the placebo group; the difference between both groups was statistically significant at P less than 0.05 by the log-rank test. The survival rate of patients was also significantly (P less than 0.05) higher in the PSK group than in the control group. The most significant laboratory finding was that polymorphonuclear leukocytes from PSK-treated patients showed remarkable enhancement in their activities, such as random and/or chemotactic locomotion, and phagocytic activity, when compared with those in the control group. In conclusion, PSK was useful as a maintenance therapy for patients after their curative surgical operations for colorectal cancer. The beneficial effects were probably due to the activation of leukocyte functions as one of the many biological-response-modifying (activities induced by PSK).

Administration, Oral

A thermoresistant mutant of ribonuclease T1 having three disulfide bonds.

Molecular-dynamic calculations predict that, if Tyr24 and Asn84 are each replaced by a Cys residue, it should be possible to form a third disulfide bond in ribonuclease T1 (RNase T1) between these residues, with only minimal conformational changes at the catalytic site. The gene encoding such a mutant variant of RNase T1 (Tyr24----Cys24, Asn84----Cys84) was constructed by the cassette mutagenesis method using a chemically synthesized gene. In order to reduce the toxic effect of the mutant enzyme (RNase T1S) on an Escherichia coli host, we arranged for the protein to be secreted into the periplasmic space by using a vector that harbors a gene for an alkaline phosphatase signal peptide under the control of the trp promoter. The nucleolytic activity of RNase T1S toward pGpC was approximately the same as that of RNase T1 at 37 degrees C (pH 7.5). Moreover, at 55 degrees C, RNase T1S retained nearly 70% of its activity while the activity of the wild-type enzyme was reduced to less than 10%. RNase T1S was also more resistant to denaturation by urea than the wild-type enzyme. However, unlike RNase T1, RNase T1S was irreversibly and almost totally inactivated by boiling at 100 degrees C for 15 min.

Base Sequence

Reversal of resistance to doxorubicin with cepharanthine in murine P388 leukemia cells.

Cytotoxic effect in vitro and antitumor effect in vivo of doxorubicin (DOX) combined with cepharanthine were investigated on DOX-resistant murine P388 leukemia (P388/R) cells. Cepharanthine was minimally cytotoxic in the cell line, but reversed DOX-resistance in a dose-related manner in P388/R cells. The administration of cepharanthine to mice bearing the P388 leukemia enhanced the antitumor activity of DOX. These results indicate that cepharanthine is an effective agent to reverse DOX-resistant cells.

Alkaloids

Reproducibility of pitch-matching test for tinnitus. Using a heptatonic scale.

We evaluated the reproducibility of measured values obtained using a heptachord pitch-matching test (PMT). Investigation of the measured values by considering the minimum unit width limits of the testing scale revealed that the coincidence ratios of the measured values of intra-daily variations, intra-weekly variations and eight values measured consecutively in one test were as high as 100%, 94.8% and 83.3%, respectively. We therefore concluded that the reproducibility of this method is satisfactory. The measured values obtained by both ordinary one-octave-interval and heptachord PMT are compared in this article.

Adolescent

Caffeine consumption among medical students.

Recently, caffeine consumption in Japan is thought to have increased. Although caffeine had been considered to be harmless, there have been studies which suggests an association between caffeine and health and give rise to vigorous discussion. However, in Japan, there have been few epidemiological studies on caffeine consumption among a general population. A questionnaire survey was conducted among medical students and the results were as follows: 1) High dose users (estimated daily caffeine use is 250 mg or more) were observed in 15.2% and the proportion was higher in males than in females. 2) The respondents gave sleepiness, dry mouth and so on, as reasons for taking caffeine beverages, and gave, as the effects of caffeine, becoming clear-headed, shaking off sleepiness, and epigastric discomfort or pain. 3) A third of respondents have experienced taking caffeine tablets and ampules to shake off sleepiness and, in males, the more caffeine they had daily, the more who reported the experience. 4) Caffeine consumption has an association with alcohol use and smoking habit among males.

Adult

Caffeine consumption and anxiety and depressive symptomatology among medical students.

Caffeine is one of the most widely consumed psychoactive substances in the world and is ingested in a variety of favorites, such as coffee, tea, cola and so on. Although it has been suggested that high dose caffeine users have more anxiety and depressive symptoms than low users, this relationship is not clear in Japan, where caffeine consumption is considered to be less than in Western countries. A questionnaire survey was conducted among medical students and 291 out of 423 initial subjects completed it. Among males, caffeine consumption was significantly and positively correlated with anxiety symptoms, when alcohol use and smoking habit were adjusted. However, there was no relationship between caffeine consumption and depressive symptoms. Among females, although there was no association between caffeine consumption and anxiety symptoms, high dose caffeine users showed less depressive symptoms than moderate and low users, when alcohol use was adjusted. It is suggested that caffeine use is one of the important factors, in researching psychological health among the general population. We need further epidemiological studies to determine whether there is a causal relationship between caffeine and psychological ill health or not.

Adult

[Multivariate analysis of gastric cancer patients with liver metastases].

In 93 cases of stomach cancer with liver metastasis, the influence of surgery and chemotherapy on the patients' prognosis was examined. Chemotherapy comprised systemic administration of mitomycin C (MMC) (39 cases), intra-hepatoarterial administration of MMC (19 cases) and intra-hepatoarterial infusion of cisplatin (CDDP) + MMC (PM intra-arterial chemotherapy) (24 cases) in the first 1-2 postoperative weeks. MMC and CDDP were given by 1-4 courses every 1-3 weeks. Examination of the prognosis factors by generalized Wilcoxon test revealed significant differences in the extent of lymph node metastasis (N0-2 vs N3,4), possible resection of primary lesion, and chemotherapeutic regimen (PM intra-arterial chemotherapy and other chemotherapeutic regimens). The response rate was 4.3% (1/23), 29.4% (5/17) and 73.8% (17/23) for MMC systemic administration, MMC intra-arterial chemotherapy and PM intra-arterial chemotherapy, respectively, with a significantly high response rate for the latter. Also for the 50% survival period, the latter showed 11.8 months compared with 2.7 months for other chemotherapeutic treatments, indicating its good prognosis regardless of possible resection of the primary lesion. Cox proportional hazard model revealed the latter alone to be a significant independent factor. The above results suggest that the PM intra-arterial chemotherapy is an effective approach to stomach cancer with liver metastasis.

Adult

[Effect of PMUE therapy (CDDP, MMC, UFT, etoposide) in terminal gastric cancer].

CDDP, MMC, UFT and Etoposide (PMUE)-combined therapy was applied to 60 cases of terminal gastric cancer to examine its effectiveness. PMUE therapy consists of i.v. injection of CDDP 75 mg/body and MMC 10 mg/body on day 1, i.v. injection of Etoposide 50 mg/body on days 3, 4 and 5 and consecutive daily administration of UFT 400 mg/body, with 3 weeks as one course. Of 42 cases having estimable lesions, 23 (53.8%) showed high rate of effectiveness (PR). Especially, of 23 cases receiving no previous treatment, 15 (65.2%) benefitted by the therapy (PR) and 9 (69.2%) of 13 non-resected cases, to a wonderful extent. Five non-resected cases showed such a reduction in tumor size as made gastrectomy possible. As for the prognosis, one year-survival rate was 34.3, 49.0 and 16.0% for all 42 cases, 23 effective cases and 19 ineffective cases, respectively, with significant (p less than 0.001) prognostic prolongation for effective cases compared with ineffective ones. Side effects were digestive symptoms (85.7%), epilation (81.0%) and myelopathy (73.8%), which were all transitory and recovered. The present PMUE therapy was regarded as one of the best combined chemotherapies for terminal gastric cancer.

Administration, Oral

[A study on 29 patients with cancers of the gastric remnant--a speculation on a remnant cancer-promoting factor from the aspect of tumor location].

We reviewed 29 patients who developed carcinomas of the gastric remnant more than 10 years after the initial gastrectomy. The median age was 59 years (29-75), with a male-to-female ratio of 3.8:1. The reason for previous operation was stomach ulcer in 16 patients, chronic gastritis in 2, stomach polyp in 2, duodenal ulcer in 5 and stomach cancer in 4 patients. Regarding the type of the original operations, Billroth's operation I (B-I) was performed for 10 patients, Billroth's II (B-II) for 18 and Roux-en Y operation for one. The site of tumor was classified into three groups, stoma (gastroenterostomy), stump (gastric cut-end except stoma) and others (the site except stoma and stump). The patients reconstructed with B-II developed significantly more carcinomas in the stoma than those reconstructed with B-I, with the incidence of 10/18 and 0/10, respectively (p less than 0.05). The interval between the initial operation and the second one was significantly longer in patients with stomal cancer than in those with stump cancer (p less than 0.05). There were no significant difference in the frequency and degree of histologic change, such as intestinal metaplasia or glandular cystification in noncancerous areas, between the B-I and B-II patients. This study suggested that cancers of the gastric remnant, especially those developed in the stoma after B-II were different from the other remnant cancers in terms of carcinogenesis or cancer promotion, and that they were probably induced by duodenogastric reflux to the gastrojejunostomized area.

Adult

[Continuous hyperthermic peritoneal perfusion with cisplatin and mitomycin C for peritoneal dissemination in gastric cancer].

Thirty-four patients with advanced gastric cancers had received continuous hyperthermic peritoneal perfusion (CHPP) for prevention or treatment of peritoneal dissemination (PD). These patients received intra-abdominal perfusion 30-40 minutes by about 10-liter saline heated to 50-52 degrees C dissolving 200-300 mg cisplatin (CDDP) and 20-30 mg mitomycin C (MMC). The perfusate was infused in the peritoneal cavity through the peritoneal cavity expander (PCE Nihon Kayaku Co. Ltd.) newly developed for sufficient irrigation in our clinic. Eleven patients with macroscopic serosal invasion without PD (P0) or with mild PD (P1) underwent prophylactic CHPP for prevention of peritoneal recurrence. (Pn means degree of PD according to The General Rules for the Gastric Cancer Study.) Twenty-three patients with moderate PD (P2) or severe PD (P3) underwent therapeutic CHPP. The prognosis of patients having undergone prophylactic or therapeutic CHPP (CHPP (+) group) was compared with those not having done CHPP (CHPP (-) group) in the historical control study. In the prophylactic study two-year-survival rates of CHPP (+) group was 90% significantly higher than 63% in CHPP (-) group. There was no significant difference between two-year-survival rates of CHPP (+) (11%) and CHPP (-) (0%) in the therapeutic CHPP. But ascites was observed to disappear in five of twelve (41.7%). Surprisingly second look operation disclosed macroscopic and microscopic disappearance of PD in three of nine (33.3%). The side-effects in those patients had consisted of leakage, bone marrow suppression, perforation of small bowel and so on. But there was no mortality after introduction of PCE. About laboratory data, rises in WBC, BUN, creatinine and LDH and drops in total lymphocytes counts and platelets were all normalized within four weeks. The maximal concentrations of total and free, which emerged at five minutes after CHPP, were 2.19 and 1.29 micrograms/ml. These results suggested that CHPP with CDDP and MMC was well tolerated and effective for prevention of peritoneal recurrence and treatment of peritoneal dissemination in the gastric cancer.

Antineoplastic Combined Chemotherapy Protocols

Reconstitution of template-dependent in vitro transcriptase activity of a yeast double-stranded RNA virus.

Isolated mature L-A viral particles from yeast have a transcriptase activity that uses endogenous L-A double-stranded RNA (dsRNA) as template. We have previously demonstrated that empty particles derived from mature L-A viral particles have replicase activity capable of synthesizing minus strand single-stranded RNA (ssRNA) on an added plus strand ssRNA template to form dsRNA. We report here that empty particles also have transcriptase activity that uses added viral dsRNA as template. The newly synthesized ssRNA was the plus strand, and some of these transcripts were converted to the dsRNA form by the replicase activity associated with the empty particles. This transcriptase activity, however, required a much higher concentration of polyethylene glycol than that used previously for the replicase activity. The mode of transcription was conservative. The enzyme transcribed ssRNA from L-A, M1, or X (a deletion mutant of L-A) dsRNAs but not from other yeast dsRNAs (L-BC, T, or W), bacteriophage Phi6 dsRNAs, or animal rotavirus dsRNAs, indicating the same template specificity as that expected for the in vivo reaction. This assay system, and the replicase assay system, will allow us to study in vitro all the enzymatic reactions essential for the viral replication cycle.

Base Sequence

[Development and clinical application of double catheter system for angiography].

Simultaneous double angiography of the two main branches of the aorta usually requires bilateral puncture of the femoral arteries. A double catheter system was devised to avoid this inconvenience. This system is composed of a 7F sheath with a valve of two small holes and two 3.5F catheters. Using this system and DSA, simultaneous double angiography of the two main branches of the aorta was performed with only one puncture site of a femoral artery in five cases. In four cases the splenic vein, superior mesenteric vein and portal vein were all opacified simultaneously. This system promises to be useful for visualization of the portal venous system and can be used for other simultaneous double angiography.

Angiography

Internal and terminal cis-acting sites are necessary for in vitro replication of the L-A double-stranded RNA virus of yeast.

Empty particles of the L-A dsRNA virus of Saccharomyces cerevisiae bind to added viral (+) strands and convert them to dsRNA (RNA replication) in an in vitro reaction that is dependent on host factors. X dsRNA (530 bp long) is a deletion derivative of L-A dsRNA (4.5 kb). By modifying our cDNA clone of X and testing template activity of T7 RNA polymerase transcripts, we have found that both the 3' end 30 bases and an internal site on the (+) strand are necessary for optimal replication [in vitro (-) strand synthesis]. Changing any one of the 3' terminal three bases eliminates template activity, but the 3' terminal five bases of M1 (a satellite virus of L-A) can replace the 3' terminal four bases of X. A subterminal stem-loop structure is also important for template activity. The internal site that enhances replication is approximately 400 bp from the 3' end and is distinct from the site necessary for binding of (+) strands to the empty viral particles.

Base Sequence

Correlation of DNA ploidy and clinical outcome in Borrmann type 4 gastric carcinoma.

The correlation between DNA ploidy pattern and clinical outcome was studied in 76 patients with Borrmann type 4 gastric carcinomas. Twenty-six tumors were diploid, and 50 tumors were aneuploid. There was no correlation among DNA ploidy and histologic type, lymph-node status, wall invasion, or clinical stage. The incidence of vascular invasion in the aneuploid tumors was significantly higher than that in the diploid tumors. Five year survival was achieved in 28% of the patients with diploid tumors and 8% of those with aneuploid tumors, respectively. Among the patients undergoing curative resection, 5 year survival rate was 54% in the patients with diploid tumors compared to 28% with aneuploid tumors. There was a significant survival advantage in patients with diploid tumors. These results indicate that DNA ploidy might be an important prognostic factor in Borrmann type 4 gastric carcinomas.

Adult