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Biomedical subjects

H Shibata

Publications and source records attributed to H Shibata.

At least 649 records · Page 36Linked to original sources

Germination of Bacillus cereus spores induced by purine ribosides and their analogs: effects of modification of base and sugar moieties of purine nucleosides on germination-inducing activity.

Purine riboside and some of its analogs were tested for their ability to induce germination of Bacillus cereus T spores. Hypoxanthine and adenine showed no germination-inducing activity either in the present or absence of D-ribose or its phosphorylated derivatives. Purine riboside and 18 analogs with modified purine base were all able to induce germination of the spores to various extents. In contrast to this, the requirement for the sugar moiety in the purine riboside appeared to be more stringent. Only those nucleosides that contained either D-ribose or deoxy-D-ribose, and certain species of azole derivatives such as 5-aminoimidazole-4-carboxamide covalently linked to the C(1') of the sugar actively induced germination.

Bacillus cereus↗

Differential count of 5,000 leukocytes for acute nonlymphocytic leukemia patients during remission.

In order to find the level of leukemic cells during remission a differential count of 5,000 leukocytes was made in 91 acute nonlymphocytic leukemia cases during their first complete remission. Patients were divided into three groups according to the level of leukemic cells, i.e., 0-1/5,000, 2-4/5,000 and 5-/5,000. A close correlation was observed between the survival of patients and the level of leukemic cells and their tendency to decrease or increase during remission. All patients in whom leukemic cells rose from 0-1/5,000 to a level higher than 8/5,000 suffered a documented relapse after 4-8 weeks. This method appears to be a good supportive examination for acute leukemia patients during remission.

Acute Disease↗

Mechanism of cholinergic stimulation of aldosterone secretion in bovine adrenal glomerulosa cells.

The effect of cholinergic stimulation on aldosterone secretion was examined in bovine adrenal glomerulosa cells. Both acetylcholine and carbachol stimulated aldosterone secretion in a dose-dependent manner. Acetylcholine-induced secretion was inhibited by atropine but not by hexamethonium, suggesting that cholinergic agonists act on muscarinic receptors. The mechanisms of cholinergic agonist action were compared with those of angiotensin II. Like angiotensin II, carbachol generated calcium signal in glomerulosa cells. When [3H]inositol-labeled cells were stimulated by carbachol, there was an immediate increase in [3H]inositol trisphosphate, followed by a relatively slow increase in [3H]inositol bisphosphate. Carbachol increased the cytosolic concentration of calcium transiently but not intracellular cAMP. Carbachol caused a rapid 3-fold increase in 45Ca fractional efflux ratio in 45Ca-prelabeled cells both in the presence and absence of extracellular calcium. Carbachol also increased calcium influx; however, carbachol-induced influx was smaller than that of angiotensin II. In a perifusion system, the time course of carbachol-induced aldosterone secretion was biphasic. However, when calcium influx was increased to a value similar to that in angiotensin II-treated cells by combination of carbachol and BAY K-8644, this combination induced a monophasic and sustained secretory pattern. These results indicate that muscarinic cholinergic agonists stimulate aldosterone secretion via the calcium messenger system, and the biphasic secretory response to cholinergic agonist is due to a smaller increase in calcium influx.

Acetylcholine↗

[Two adult cases of malignant hepatic mixed tumor].

Two adult males, aged 20 and 47 years, suffered from malignant hepatic mixed tumor. The common initial symptom was low grade fever and a large palpable tumor in the right quadrant of the abdomen. Macroscopically, these tumors were huge and elastic firm in consistency. Microscopic findings confirmed that the tumor cells possessed totipotential cell characteristics. Therefore, it might be conceivable that these two cases were malignant hepatic mixed tumor originating from the hepatic premordial cell.

Carcinoma, Hepatocellular↗

[Effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome].

This study was designed to evaluate the effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome (MDS). The subjects were 33 patients (19 acute myelocytic leukemia (AML), 9 MDS, 3 atypical leukemia and 2 unclassified leukemia). The age range was 19 to 84 years with a mean age of 51.5 years. We administered low-dose Ara-C (5-10 mg/m2/12 h s.c. or i.v.) for 13 to 35 days with a mean of 16.7 days. Complete remission and partial remission were obtained in 8 of 31 (25.8%) and in 9 of 31 (29.0%) respectively. A high response rate was found in M2 types showing a tendency for mature and refractory anemia with excess blasts in MDS according to the FAB classification. In our cases, severe pancytopenia in peripheral blood as a result of Ara-C was observed before normal hematopoiesis recurred. From the above results, the mechanism of low-dose Ara-C may induce remission by a cytotoxic rather than a differentiation effect. This treatment can be offered to patients with refractory, atypical leukemia and MDS with limited toxicity.

Adolescent↗

[Phase II study on oral administration of MCNU (ranomustine) tablet. Hanshin Cooperative Study Group on Hematological Disorders].

A phase II study of MCNU tablet has been performed on 70 patients with hematological disorders including mostly myeloproliferative disorders. MCNU tablet was given p.o. at a dose of 50 mg daily for 2-6 days (total 100-300mg) as one course with average intervals of 3 to 5 months or more for patients responding to this drug. The effective rates were 72% in 18 patients with chronic myelogenous leukemia, 88% in 25 patients with polycythemia vera and 68.5% in 19 patients with essential thrombocythemia. Side effects of MCNU tablet were nausea and vomiting (31%) which had a dose-dependent relationship, mild liver dysfunction (5%) and elevation of BUN and creatinine (2%) which were not serious. The results were almost comparable to those of the phase II study of MCNU given intravenously.

Administration, Oral↗

[A phase II study of epirubicin in acute leukemia: a cooperative group study].

A new doxorubicin analogue, epirubicin (EPI), has been evaluated in 11 institutions throughout Japan in a phase II study in patients with acute leukemia. A total of 41 patients were entered into this study between January 1983 and July 1985, and 34 were considered evaluable. Two patients were added for evaluation of toxicity. There were 25 males and 9 females with a median age of 43 years. Of the 34 evaluable patients, 24 had previously been treated with intensive combination chemotherapy, 21 with anthracyclines. The remaining ten were previously untreated patients. Underlying diseases were acute lymphocytic leukemia (ALL) in 15, acute non-lymphocytic leukemia (ANLL) in 17 and blastic crisis of chronic myelogenous leukemia (CML/BC) in 2. EPI was administered intravenously in two schedules, a high-dose regimen consisting of 24 to 60 mg/m2/day for 3 to 5 days and a low-dose regimen involving 11-17 mg/m2/day for 5 to 8 days. Responses were obtained in 5 (33.3%) of 15 patients with ALL, 3 of these attaining complete remission, 2 (11.8%) of 17 patients with ANLL and one (50.0%) of 2 patients with CML/BC. Out of the 21 patients who had received previous anthracyclines, 4 (19.1%) attained responses. Also, responses were obtained in 23.5% with the higher doses as well as 24% with the lower doses. The remission duration of responders was 1, 1, 3, 3, 3, 16+, 17 and 26 weeks, respectively. The major non-hematologic toxicity was stomatitis which occurred in 15 patients, in 11 of whom the symptoms were severe (Grade 3 or 4). This stomatitis was thought to be the dose limiting factor. On the basis of the above observations, we concluded that EPI was active against acute leukemia, especially ALL. Stomatitis was considered to be the dose-limiting factor, especially in the high-dose regimen. Toxicity was tolerable in the low-dose regimen.

Acute Disease↗

[A phase II study of epirubicin in malignant lymphoma].

A new anthracycline analog, epirubicin (4'-epi-Adriamycin) was evaluated at eleven institutes in a phase II clinical study in patients with malignant lymphoma. Epirubicin was administered intravenously mainly with using the following two regimens; 50 to 60 mg/m2 every three weeks and 40 mg/m2 weekly. A total of 46 cases were entered into the study and 41 cases were evaluable. Clinical responses, complete plus partial remissions, were observed in 27 cases (65.9%) with 8 of these showing complete remission. There was no significant difference of response between the two regimens. Response rates taking into account previous chemotherapy were 90.9% (10/11) in previously nontreated cases, 61.9% (8/13) in cases previously treated with non-anthracyclines and 52.9% (9/17) in cases treated with anthracyclines. The major adverse effect was bone marrow suppression; leukopenia was observed in 83.8%, anemia in 60.5% and thrombocytopenia in 15.4%. Other adverse effects frequently observed were anorexia (59.0%), nausea-vomiting (48.8%) and alopecia (55.6%). These adverse effects seemed milder than those produced by doxorubicin. The results indicated that epirubicin seemed to be a markedly useful drug against malignant lymphoma.

Adult↗

[Treatment with K-18 (IgG-melphalan) in recurrent cases of hematopoietic malignancies].

K 18, an IgG-Melphalan conjugate was administered to 30 patients, who had recurrent hematopoietic malignancy. Ten out of the 30 patients received single doses of 1 to 20 enteric tablets containing 10 mg of K 18, as a phase I study. No side effects were observed. K 18 was administered every day to the remaining 20 patients in order to evaluate the side effects and therapeutic effects, as a phase II study. One patient attained partial remission. Although no remission effect was obtained in 14 of the 20 patients, antitumor effects such as a decrease in leukemia cells, were observed in 4 of 20 patients. As to side effects, neither recurrence of tumor nor cumulative toxicity were shown in one patient with NHL who received only K 18 for 14 months as maintenance therapy. Evaluation of antitumor effect was difficult in the case of the remaining 4 patients. In the 20 cases who entered the phase II study, a decrease in neutrophils was observed in 2 patients, a slight decrease in platelets in 3 patients and increased transaminase activity in one patient as side effects of K 18. In brief, compared with Melphalan, K 18 has between 1.3 and 2 times a more potent therapeutic effect, with extremely low side effects.

Administration, Oral↗

Total body irradiation for allogeneic bone marrow transplantation in acute leukemia: a co-operative study from the TBI Subcommittee in Japan.

By means of national survey, records of 78 acute leukemia patients who underwent allogeneic bone marrow transplantation (BMT) from September 1975 through September 1983 were collected from 14 participating institutions in Total Body Irradiation (TBI) Subcommittee in Japan. Patients were classified into 37 of acute lymphocytic leukemia (ALL), and 41 of acute non-lymphocytic leukemia (ANLL). One-year survivals were 51% and 33% in ALL and ANLL patients, respectively. Uninfected patients in remission had significantly better survival than infected ones and/or in relapse. Overall incidence of interstitial pneumonia was 43%. Rejection and relapse were encountered in 26% of patients. Concerning cause of death, interstitial pneumonia was the most frequent cause (44%). Uni- and multivariate analyses strongly suggested that favorable prognostic factors were remission, uninfection, preparation of low-dose-rate fractionated TBI and cyclophosphamide, and mild graft-versus-host disease (GVHD) for acute leukemia patient treated with allogeneic BMT.

Acute Disease↗

Risk factors associated with interstitial pneumonia following allogeneic bone marrow transplantation for acute leukemia in Japanese experience.

Records of 101 patients with acute leukemia who received allogeneic bone marrow transplantation (BMT) with preparation using cyclophosphamide and total body irradiation (TBI) from September 1975 through July 1984 were collected into Japanese Bone Marrow Transplant Registry from 15 of the participating hospitals. These patients were divided into two groups by year of BMT. Group I included nine acute lymphocytic leukemia (ALL) and nine acute non-lymphocytic leukemia (ANL) patients who received BMT before 1980. Group II consisted 39 ALL and 44 ANL patients who were treated after 1981. One-year survivals were 11% and 58% in groups I and II, respectively (p less than 0.001). Probabilities of developing interstitial pneumonia at one year were 93% and 37% in groups I and II, respectively (p less than 0.001). Of 14 patients who developed interstitial pneumonia in group I, twelve (86%) died of interstitial pneumonia. Fifteen of 22 (68%) were fatal in group II. Using proportional hazard regression model, year of BMT (p = 0.0001) and selection of platelet donor with negative cytomegalovirus (CMV) titer (p = 0.0215) were found to be significant risk factors associated with interstitial pneumonia. The present analysis indicated that change in the selection of patients, e.g., in remission without infection at the time of BMT, as well as treatment modality, e.g., fractionated TBI, and selection of platelet donor with negative CMV titer, resulted in the significant improvement in the survival and decreased incidence of interstitial pneumonia.

Acute Disease↗

[A phase III study of BHAC-MMP (behenoyl-ara-C, mitoxantrone, 6-mercaptopurine prednisolone) in acute leukemia. Hanshin Cooperative Study Group of Hematological Disorders].

BHAC-MMP therapy, a combination of behenoyl-ara-C, mitoxantrone, 6-mercaptopurine and prednisolone, was applied to 49 patients with acute leukemia for remission induction. Complete remission was obtained in 6 out of 11 previously untreated patients (55%), and in 16 of 38 pretreated patients (42%). Median duration of complete remission was 41 weeks in previously treated patients, while 67% of untreated patients were still in complete remission. Most frequent side effects other than hematological toxicities were gastrointestinal disturbances, and GPT elevation etc., although most of these were not severe. In conclusion, BHAC-MMP therapy seems to be very promising for remission induction or for possible intensification treatment for acute leukemia.

Acute Disease↗

[A phase II study of mitoxantrone in acute leukemia. Hanshin Cooperative Study Group of Hematological Disorders].

A phase II study of mitoxantrone was conducted on acute leukemia. Mitoxantrone 4 mg/m2/day was administered for 5 consecutive days in most cases. For cases showing insufficient decrease of leukemic cells even at nadir, a second course of the same regimen was given. Enrolled were 38 cases in total, of which 34 were evaluable. In 14 cases for first remission induction, the drug efficacy was evaluated at the completion of the first or second course, then further combination drug therapy followed immediately. Of 14 cases for first remission induction, 6, or 43%, achieved CR and of 20 cases for reinduction of remission, 4, or 20%, achieved CR. Two out of 7 cases of ALL (29%) and 8 out of 27 cases of ANLL (30%) achieved CR. Of 19 cases with previous anthracycline therapy, 4 cases, or 21%, achieved CR, showing that the cross-resistance was partial. Gastrointestinal symptoms were the main side effects, but cases of symptoms severer than grade 3 were very rare. Cardiotoxicity occurred at a rate as low as 11%. Mitoxantrone thus appears to be a promising drug for the treatment of acute leukemia.

Acute Disease↗