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Biomedical subjects

M Tabata

Publications and source records attributed to M Tabata.

At least 217 records · Page 12Linked to original sources

Antiulcerogenic compounds isolated from Chinese cinnamon.

Two active compounds that prevent serotonin-induced ulcerogenesis in rats were isolated from Chinese cinnamon (the stem bark of Cinnamomum cassia) and identified as 3-(2-hydroxyphenyl)-propanoic acid and its O-glucoside. The former compound, administered orally or parenterally to rats at a remarkably low dose (40 micrograms/kg body weight), also inhibited gastric ulcers induced by the other ulcerogens such as phenylbutazone, ethanol, and water immersion stress, although it failed to prevent indomethacin-induced ulcers. Pharmacological studies have shown that 3-(2-hydroxyphenyl)-propanoic acid hardly inhibited the secretion of gastric acid, but promoted the gastric blood flow. These results suggest that the antiulcerogenic effect of this compound is probably attributable to the potentiation of defensive factors through the improvement of the circulatory disorder and gastric cytoprotection.

Animals↗

Purification and properties of human erythrocyte arginase.

An efficient method for purification of human erythrocyte arginase was developed. This method included two new procedures, hydrophobic chromatography and immunoaffinity chromatography, and yielded 0.7 mg of homogeneous arginase protein from 2.1 L of haemolysate. The molecular weight of native arginase was estimated to be 105,000 by gel filtration on a Sephadex G-150 column, and that of its subunit 35,000 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. This indicates that the native enzyme is composed of three homologous subunits. Amino acid composition of human erythrocyte arginase was found to be very similar to that of liver arginase of several other mammals. After dialysis against distilled water, the purified arginase still retained its enzymatic activity which was decreased by EDTA and reversibly restored by Mn(II) ion. A specific polyclonal antibody for use in an immunoassay was also produced. This antibody revealed one single band on immunoelectrophoretic analysis of the acetone powder extract, suggesting absence of arginase isoenzymes in human erythrocytes.

Amino Acids↗

[Effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) in patients receiving chemotherapy--phase I study].

Seventeen patients with advanced malignancy were treated with recombinant human granulocyte colony stimulating factor rhG-CSF (KRN 8601) infused intravenously over a period of 30 minutes once daily at the dose level/25 micrograms, 50 micrograms, 100 micrograms, 200 micrograms, 400 micrograms, 800 micrograms/m2 for 14 consecutive days, and the effect was compared to the period without rhG-CSF treatment. The maximum numbers of peripheral leukocyte (granulocyte) showed a dose-related increase and the nadir of leukocyte counts escalated with shortening of the period. After stopping infusion, the neutrophil count dropped to the base line level within two or three days. RhG-CSF did not affect other components of peripheral blood such as monocyte, lymphocyte, eosinophil, and hemoglobin value and platelet counts. Transient bone pain occurred in two patients receiving a dose of 800 micrograms/m2. The biochemical changes detected were increased total alkaline phosphatase activity in serum, which appeared in parallel with the increase of neutrophil numbers, and less elevation of total uric acid values. We conclude that an optimal dose of rhG-CSF is 100 micrograms/m2 (average maximum peripheral granulocyte count, 10799/microliters; nadir granulocyte count, 3772/microliters; period of neutropenia, 2.6 days), and rhG-CSF is useful for acceleration of neutrophil recovery and prevention of infection from chemotherapy.

Adolescent↗

[A study to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation].

Drug resistant phenomenon to antitumor agents remains a major problem in cancer chemotherapy. In this study, we attempted to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation (ABMT). The main regimen consisted of Cyclophosphamide 60 mg/kg/day and thio-TEPA 6 mg/kg/day which were infused for 3 consecutive days. Three patients with malignant lymphoma, four with breast cancer, two with gastric cancer and one with ovarian cancer. All of whom were refractory to conventional chemotherapies were treated. The overall response rate was 70%. Severe bone marrow suppression, mucositis and diarrhea were observed in all patients, but these were not life-threatening and clinically manageable. Furthermore, the administration of granulocyte colony stimulating factor (G-CSF) has significantly (p less than 0.05) shortened the duration of leukopenia, and has been judged to be useful for reducing severe infections and for shortening the period stayed in clean room. Our results indicates that high-dose chemotherapy with ABMT is an effective method for overcoming drug resistance.

Adult↗

[A study of complete responders in cases of metastatic breast cancer treated with combination chemotherapy].

Twenty-eight patients with a metastatic breast cancer who have achieved a complete remission from a combination chemotherapy that included doxorubicin have been analyzed to ascertain the factors which affect the duration of the response and the survival time. The median duration of a complete remission was 26 months. Relapses occurred in 17 patients (61%), of which the median duration of the response was 18 months and 71% of the relapses occurred at the sites of the prior dominant disease. Most of the patients suffered a relapse while they were receiving maintenance chemotherapy. The number of metastasized organs were one or two in 89% of the patients. The dominant sites of the disease were mainly the visceral (61%) and soft tissue (29%), and the duration of survival was found to be longer in patients with a visceral metastasis. In the group of patients who experienced a recurrence 2 years or more after their operation showed a statistically longer remission and survival time than those who experienced a recurrence within 2 years. The duration of survival from the start of chemotherapy was 45.5 months for complete responders and 21 months for partial responders. This difference was statistically significant (p less than 0.001), though no difference was found between partial responders and "no-change" patients (18.5 months). The tendency towards a relapse at the site of the initial involvement and while receiving maintenance therapy suggests that the majority of patients with a metastatic breast cancer who achieved a complete remission with this combination chemotherapy still have a substantial subclinical residual tumor. Maintenance treatment should be investigated to ascertain the procedures and duration of therapy. Thus, these results have indicated that it is necessary to achieve a complete remission in order to obtain a long term survival.

Adenocarcinoma, Scirrhous↗

[Phase I and pharmacokinetic study of KRN8602, a new morpholino anthracycline].

Phase I clinical trial of a new semi-synthetic morpholino anthracycline derivative, KRN8602, was performed. Sixteen patients with advanced malignant neoplasms refractory to standard chemotherapies received 27 courses at doses ranging from 1.5 mg/m2/day to 18 mg/m2/day by bolus injection for three consecutive days. The dose limiting toxicity was leukopenia, and a maximally tolerated dose was 18 mg/m2/day (day 1-3). The recommended dose and schedule for a phase II study is determined to be 12 mg/m2/day for three consecutive days at 3-4 weeks intervals. Among non-hematologic toxicities, nausea and vomiting were severe, but stomatitis and alopecia were rarely observed. Clinical signs of cardiotoxicity were not seen.

Aged↗

[4'-(9-acridinylamino)-methanesulfon-m-aniside (AMSA) combination salvage therapy in refractory acute non-lymphocytic leukemia in adults].

Eight patients with acute non-lymphocytic leukemia in adults refractory to Daunomycin (DM)-based conventional regimens were treated with AMSA-based regimens. Complete remission (CR) was obtained in 4 (50%) and partial remission (PR) in 2 (25%). The median time to CR was 26.5 days and 3 cases achieved CR in the first cycle. The median duration of CR was 8.3 months. Hematologic toxicity was severe and the nadir (median) of leukocytes and platelets was 0.15 x 10(3)/microliters and 15.5 x 10(3)/microliters, respectively. Other adverse effects were mucositis, nausea.vomiting and hepatotoxicity which occurred over 50%, while cardiac toxicity was not observed. This study indicates that AMSA is clinically non-cross-resistant to DM and considered to be an active drug for salvage therapy.

Adolescent↗

[The importance of uterine vascular systems in the maintenance of pregnancy].

The mesometrial artery (MA), which is the final part of the uterine artery in guinea pig, supplies nutrients and oxygen to the fetus and placenta during pregnancy. Accompanying fetal growth, MA increases 8-fold in diameter, and 30- to 50-fold in weight, protein content and deoxyribonucleic acid (DNA) content. The importance of MA in the maintenance of pregnancy was examined by comparing the proliferative rate of MA during pregnancy and abortion induced by antiprogesterone RU38486 30 mg/kg. MA was incubated in Medium 199 with 185kBq/ml 3H-thymidine for 4h and the rate of 3H-incorporation into MA was used as the proliferative rate. The proliferative rate of MA during the first trimester (day less than 20) was 2,825 +/- 1,036 Bq/mg.h, which is almost 100 times higher than the rate in diestrus animals. During the later course of pregnancy, the proliferative rate decreased logarithmically, being 352 +/- 58 (40 less than or equal to d less than 50), 158 +/- 23 (50 less than or equal to d less than 60) and 75 +/- 10 (60 less than or equal to d). The proliferative rate of MA was measured also in animals which received RU38486 30 mg/kg at 24-48 h prior to the measurement and whose fetuses were still alive. The proliferative rates of MA in such animals decreased markedly to 141 +/- 21 (40 less than or equal to d less than 50) and 37 +/- 8 (50 less than or equal to d less than 60) (p less than 0.01), which means that the proliferation of MA is reduced even before the death of the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗

Antioxidant activity of synovial fluid, hyaluronic acid, and two subcomponents of hyaluronic acid. Synovial fluid scavenging effect is enhanced in rheumatoid arthritis patients.

To test the scavenging of reactive oxygen species (ROS), we added synovial fluids from patients with rheumatoid arthritis (RA) and osteoarthritis, as well as hyaluronic acid (HA) and its 2 subcomponents, D-glucuronic acid and N-acetyl-D-glucosamine, to 2 ROS-generating systems, activated neutrophils and xanthine-xanthine oxidase. Synovial fluid from RA patients, HA, and D-glucuronic acid markedly decreased the O2-, H2O2, OH., and chemiluminescence measured in both systems. HA and synovial fluid, which are known to be susceptible to degradation by excessive ROS in RA patients, also seem to play an active role in protecting articular tissues from oxidative damage.

Acetylglucosamine↗

The effects of the proliferation of the radial arteries of the placenta on oxygen transport to the fetal guinea pig.

The adjustment of placental blood flow during pregnancy is related to progressive structual changes in the placental arteries. In guinea pig, massive growth has also been shown to be associated with widening of the uterine radial arteries. The rate of 3H-thymidine incorporation into uterine radial arteries during pregnancy was studied in guinea pig as a measure of local DNA synthesis. And the oxygen partial pressure was used to investigate how the oxygen transport is done between mother to fetus. During the first half of pregnancy, 3H-thymidine was incorporated at the rate of about 1,000 Bq/mg.h. The initial rate during pregnancy is similar to the rate observed during estrus. This observation suggest that the same factors stimulate DNA synthesis during gestation and estrus. The rate of 3H-thymidine incorporation per vessel length increased with the injected dose of estradiol benzoate. We suppose that estradiol is one of the control factors in DNA synthesis in uterine radial artery. The oxygen partial pressure in amniotic fluid was about 110 mmHg on various days of gestation and no significant changes were observed with time. For these reasons, estrogen is supposed to be one of the control factors in oxygen transport to fetus.

Amniotic Fluid↗

Ovarian blood flow and oxygen transport to the follicle during the preovulatory period.

The mechanism of ovulation, especially the mechanism of follicle rupture, is still uncertain. Ovarian blood flow, ovarian vessel morphology and oxygen transport to follicle were therefore studied during the preovulatory period. Japanese white rabbits, weighing 3.0-4.4 kg, were used as the experimental animal. Ovulation was induced by the administration of PMS (100 iu, IM) and hCG (100 iu, IV). The ovulation was observed at 10-13 h after hCG administration. Continuous measurement of ovarian blood flow was facilitated by the crossed-thermocouple inserted into the unilateral ovary. The variation of ovarian blood flow was expressed as the percentage ratio based on the post-mortem value ( = 0%) and the initial value prior to hCG administration ( = 100%). Histologic changes of ovarian blood vessels were observed at intervals of every 2 hours after hCG administration. Oxygen transport to follicle was compared at 7 and 12 h after hCG administration. The ovarian blood flow increased rapidly within 1 h following hCG administration. High percentage increases were demonstrated during 2 h to 5 h, showing a peak value of 155.3 +/- 12.7% at 3 h. The ovarian blood flow decreased gradually from 5 h to 8 h and then was maintained at about 110% after 8 h. The perifollicular and stromal vasodilatations were confirmed at 2 h and moderate dilatation was observed during 4 h to 6 h. At 10 h, just prior to ovulation, vasodilatation became most remarkable especially at the apical vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Unconjugated bilirubin in hepatic bile with brown pigment gallstones and cholangitis.

To investigate the role of cholangitis in hydrolysis of bilirubin in bile with brown pigment gallstones, bilirubin composition and bacterial growth in hepatic bile with and without cholangitis were studied. The study included 38 brown pigment gallstone cases (28 without cholangitis and 10 with cholangitis). The proportion of unconjugated bilirubin in hepatic bile with cholangitis (16.9 +/- 8.5%, mean +/- SD) was significantly higher than that without cholangitis (3.7 +/- 1.8%, P less than 0.001). A positive correlation was found between bacterial population with beta-glucuronidase activity and the proportion of unconjugated bilirubin in bile in cases of brown pigment stones with cholangitis (P less than 0.05) but not in those without cholangitis despite the fact that bacterial species and population are similar regardless of the presence of cholangitis. In cholangitis, pH of bile becomes lower toward the optimal pH of bacterial beta-glucuronidase. Together the lower concentration of bile acid and the lower pH in bile result in lower solubility of unconjugated bilirubin, promoting its precipitation. Thus occasional bouts of cholangitis may result in periodic deposition of bilirubinate on brown pigment stones with layered structures by inducing cyclic changes of bile composition in situ.

Bacteroides↗

[Phase II study of combination chemotherapy with epirubicin, cyclophosphamide and ftorafur in metastatic breast cancer].

Twenty-nine patients with metastatic breast cancer were treated with a combination chemotherapy consisting of Epirubicin 50 mg/m2 IV on day 1, Cyclophosphamide 500 mg/m2 IV on day 1 and Ftorafur 800 mg/day PO every day (ECF therapy). The therapy was repeated every 3 weeks until progression or until a cumulative dose of 700 mg/m2 for epirubicin. Of 25 evaluable patients, there were one with complete response (CR), 11 with partial response (PR), 10 with no change and 3 with progressive disease (PD). The overall response rate (CR + PR) was 48%, and the median duration of response was 47 weeks. The median survival time was 78 weeks for responders and 60 weeks for non-responders, and the difference was statistically significant (p = 0.02). Leukopenia, alopecia, nausea and vomiting were commonly observed, but these side effects were better tolerated than those accompanying ACF therapy. As for cardiotoxicity, there were no acute abnormal E.C.G. changes and no congestive heart failure occurred. The median cumulative dose of Epirubicin was 510 mg/m2. These results indicate that ECF therapy is as effective as ACF therapy for metastatic breast cancer with considerably better tolerability.

Adult↗