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Biomedical subjects

K Toyoda

Publications and source records attributed to K Toyoda.

At least 235 records · Page 13Linked to original sources

[Phase II study of mitoxantrone for hematologic malignancies].

A phase II study of mitoxantrone (MIT) was performed in 21 patients with hematologic malignancies refractory to combination chemotherapy including anthracyclines. MIT was administered intravenously at doses of 8 to 13 mg/m2 on day 1 for 12 malignant lymphoma patients, and 1 to 3.3 mg/m2 on day 1 through 5 for 7 acute leukemia patients and 2 malignant lymphoma patients. Four malignant lymphoma patients (2 each of Hodgkin's disease and non-Hodgkin's lymphoma) achieved partial response lasting 19, 14, 8+, and 4 weeks, respectively. Although no definite response was obtained in acute leukemia patients, a marked cytoreduction was observed in 2 patients. Myelosuppression was a major toxicity, however, life-threatening toxicities were not observed in this study.

Acute Disease↗

Identification of carcinoembryonic antigen (CEA) in bile of patients with malignant biliary tract disease.

As a diagnostic aid of malignant hepato-biliary tract disease, carcinoembryonic antigen (CEA) levels in the bile and serum were evaluated in 12 patients with benign and 19 patients with malignant hepato-biliary diseases. Of the 12 patients with benign disease, 3 had a residual choledocholithiasis. CEA levels were determined in 7 patients with cancer of the head of pancreas or of the duodenal ampulla. Bile samples were obtained via biliary tract drainage after allowing for sufficient time to exclude the effects of pre-existing bile stasis or inflammation. The average serum CEA levels from 8 patients with benign disease were 1.5 +/- 0.23 ng/ml in contrast to 3.3 +/- 0.55 ng/ml in 18 with a malignancy (p less than 0.05). The average CEA levels in bile from 9 patients with benign and 19 with a malignancy were 1.7 +/- 0.31 ng/ml and 7.6 +/- 1.70 ng/ml respectively (p less than 0.01). In 3 with residual choledocholithiasis, serum and bile CEA levels were 2.0 +/- 0.46 ng/ml and 13.1 +/- 6.47 ng/ml. The serum and bile CEA levels from 7 patients with cancer of the head of the pancreas or of duodenal ampulla were 2.5 +/- 0.32 ng/ml and 8.8 +/- 3.3 ng/ml, respectively. Although measurement of both serum and bile CEA levels in patients with hepato-biliary tract disease proved to be useful for differentiation of malignant from benign disease, the high value obtained strongly suggests the presence of a malignancy in addition to the residual choledocholithiasis and cancer of the head of the pancreas or of the duodenal ampulla.

Adult↗

[Clinical effect of acetylspiramycin on primary atypical pneumonia in children (author's transl)].

Clinical effect of acetylspiramycin, one of macrolide antibiotics, primary atypical pneumonia and serologically proven Mycoplasma pneumonia in children was studied. Twenty-four cases of these pneumonia (PAP 11, MP 13) in children were selected and acetylspiramycin was given in dose of approximately 30 mg/kg/day orally. Clinical response was evaluated in terms of improvement in fever, cough and chest X-ray. Clinical response was excellent in 4, good in 5, fair in 14 cases and none in 1 case. No definite adverse effect was observed, however 3 cases showed skin rashes. Two cases showed evanescent small erythematopapulous rash and 1 case developed urticaria on the 2nd to 4th day after this drug was given. These skin rash seemed one of the manifestation of Mycoplasma infections, rather than adverse side effect. One case showed elevated transaminase activity before acetylspiramycin was given and improved on the 2nd week, although this drug was continued. No other side effect was observed. We were able to use acetylspiramycin only in the form of 200 mg tablet and difficulty of the administration was encountered in children under 5 years of age. Other form (dry syrup, etc.) of this drug should be considered for the clinical use in children. In conclusion, acetylspiramycin was effective and safe for the treatment of primary atypical pneumonia and Mycoplasma pneumonia.

Adolescent↗

Occurrence of ANTI-AHLG in renal transplant patients on AHLG (anti-human lymphocyte globulin).

Two patients with kidney transplants were prescribed anti-human lymphocyte gamma-globulin (AHLG) as an adjunct immunosuppressive treatment. AHLG was prepared from cultured human lymphocytes an antigen and successive anti-AHLG levels were measured using passive hemagglutination tests during and after the AHLG treatment. Anti-AHLG levels began to increase after 10-14 days of daily AHLG administration. Thereafter, the levels tends to decrease transiently by the further administration of AHLG. The titer rose again after the discontinuation of AHLG administration reaching a plateau which continued for a considerable length of time. Pretreatment levels were reverted after more than three months. The anti-sheep RBC Ab and anti-horse RBC Ab levels followed the same pattern as that seen with anti-AHLG Ab. The anti-AHLG Ab proved to be specific anti-horse gamma-globulin Ab. Alterations in the anti-AHLG levels can thus be used to monitor the optimal dosage and period of administration as well as to predict the anaphylactic reaction due to AHLG treatment. Keeping the anti-AHLG level low is mandatory to maintain good immunosuppressive conditions yet avoid anaphylactic reactions.

Adolescent↗

Takayasu's disease: association with HLA-B5.

The frequency of HLA-B5 (66%, n = 38) in Japanese patients with Takayasu's disease was significantly higher than in controls (32%, n = 160). The level of significance was x2 = 13.53, P less than 0.0005 and corrected P less than 0.009.

Aortic Arch Syndromes↗

A study on HL-A system in Japanese.

Two hundred unrelated Japanese individuals were HL-A typed with UCLA Research Tray T3 (Terasaki's Tray), which contains specificities added after the Fifth International Workshop. Phenotype, gene and haplotype frequencies were calculated with standard errors and delta values. HL-A9, HL-A5 and W10 had a higher frequency and HL-A1, 3 and 8 had a lower frequency in Japanese than in Caucasians. The frequent haplotypes were HL-A9-HL-A5, HL-A9-HL-A7 and HL-A2W10. HL-A9-HL-A5 showed very positive high linkage disequilibrium parameter (delta value) and HL-A9-W10 showed negative high value. The sera designated as anti-HL-A, W5 and W15 in the T3 Tray which react identically in Caucasians showed different patterns of reaction when tested in the Japanese population. Five hundred Japanese parous women's sera were tested for cytotoxic antibodies. Some Japanese antisera showed high correlation coefficient values on HL-A2, HL-A9, HL-A10, HL-A11 and HL-A12. The women providing the anti-HL-5 complex sera and their immunizing persons were HL-A typed. These complex sera reactions were compared with the antisera in the T3 Tray. A new group of sera (SN-1), "operationally monospecific" and cross-reacting with W22, was found in the present study. Population and family studies suggested that the sera SN-1 are third in frequency within the second series (phenotypic frequency 17-22%) and show high delta values with HL-A11 in the Japanese population.

Epitopes↗

Carcinogenicity study of beta-cyclodextrin in F344 rats.

The carcinogenicity of beta-cyclodextrin, a cyclic, water-soluble carbohydrate comprising seven glucose units, was examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given the compound in their diet at concentrations of 0 (control), 2.5 or 5% for 104 wk. Surviving rats were then given a basal diet for a further 5 wk and killed at 109 wk. The dose levels were selected from the results of a 13-wk subchronic toxicity study. Dose-dependent inhibitory effects of beta-cyclodextrin on growth were observed in both sexes of the treated groups. The survival rates, mean survival times and range, however, demonstrated no significant differences between the control and treated groups. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in this strain of rat, and no statistically significant increase in the incidence of any tumour was found for either sex of the treated groups. Thus, it is concluded that under the present experimental conditions, the high dose, about 340-400 times higher than the current daily human intake from ingestion as a food additive and from pharmaceutical use, does not have any carcinogenic potential in F344 rats.

Administration, Oral↗

Lack of carcinogenicity and increased survival in F344 rats treated with 5-fluorouracil for two years.

The carcinogenicity of 5-fluorouracil (5-FU), a compound employed as an antineoplastic drug, was investigated in F344 rats of both sexes. 5-FU was administered to groups of 50 male and 50 female rats ad lib. for 104 weeks, added to drinking water at concentrations of 0 (control), 62 and 125 ppm, these dose levels being selected on the basis of results of a 13-week subchronic toxicity study. Body weight gains were slightly depressed in the 125 ppm group of both sexes. While not statistically significant in females, final survival rates at week 111 in the 125 ppm group of both sexes were higher than those in the control group, suggesting an ability of 5-FU to prolong the lifespan. Histopathologically, a decreased incidence of islet cell adenomas in males and increased incidences of pituitary gland adenomas and pheochromocytomas in females were observed in the 62 ppm group without dose dependence. There was no significant induction of any other neoplastic or non-neoplastic lesions. These results indicate a lack of carcinogenicity of 5-FU under the present experimental conditions using rats.

Adenoma↗

High frequency of ras mutations in forestomach and lung tumors of B6C3F1 mice exposed to 1-amino-2,4-dibromoanthraquinone for 2 years.

1-Amino-2,4-dibromoanthraquinone (ADBAQ) is an anthraquinone-derived vat dye, and a potent carcinogen in laboratory animals. In a 2-year study with dietary exposure to 10,000 or 20,000 ppm ADBAQ, increased incidence of forestomach and lung tumors were observed in B6C3F1 mice. The present study indentified genetic alterations in H-ras and K-ras proto-oncogenes in ADBAQ-induced tumors. Point mutations in ras proto-oncogenes were identified by restriction fragment length polymorphism, single-stranded conformational polymorphism analysis and cycle sequencing of polymerase chain reaction-amplified DNA isolated from paraffin-embedded squamous cell papillomas and carcinomas in the forestomach, and alveolar/bronchiolar adenomas and carcinomas in the lung. A higher frequency of ras mutations was identified in ADBAQ-induced forestomach (23/32, 72%) and lung tumors (16/23, 70%) than in spontaneous forestomach (4/11, 36%) and lung tumors (26/86, 30%). H-ras codon 61 CTA mutations were detected in (4/8, 50%) ADBAQ-induced forestomach squamous cell papillomas and (10/24, 42%) squamous cell carcinomas, but not in the spontaneous forestomach tumors examined. H-ras codon 61 CGA mutation (6/24, 25%) was also detected in ADBAQ-induced forestomach squamous cell carcinomas. K-ras codon 61 A to T transversions and A to G transitions were prominent in ADBAQ-induced lung alveolar/bronchiolar adenomas and alveolar/bronchiolar carcinomas. The major finding of A to T transversions or A to G transitions in forestomach and lung tumors suggests that ADBAQ or its metabolites target adenine bases in the ras proto-oncogenes and that these mutations play a dominant role in multi-organ

Adenocarcinoma, Bronchiolo-Alveolar↗

Toxic effects of benzyl and allyl isothiocyanates and benzyl-isoform specific metabolites in the urinary bladder after a single intravesical application to rats.

Allyl isothiocyanate (AITC) is known to be weakly carcinogenic, whereas benzyl isothiocyanate (BITC) has been suggested to exert carcinogenicity toward the rat urinary bladder. To elucidate direct toxic effects of isothiocyanates (ITCs), BITC, AITC, or BITC-metabolites conjugated either with glutathione, cysteinylglycine, cysteine, or mercapturic acid were intravesically instilled into female F344 rats. Exposure to AITC and BITC at 2.8 mg/kg body weight, and the same mol quantity (37 micromol/kg) of BITC-metabolites was for 2 h. Nineteen hours thereafter, the animals were intravenously administered 5-bromo-2'-deoxyuridine (BrdU) and killed 1 h later. BITC caused more profound toxic damage than AITC. Among the BITC-metabolites, cytotoxicity was evident with intermediate glutathione or cysteinylglycine conjugates, whereas the mercapturic acid, considered to be the major final urinary metabolite, exerted little effects. BrdU labeling was essentially dependent on the degree of cytotoxic potential of each compound. Considering the previous study results demonstrating the generation of free BITC from metabolites in urine, the present results support the idea that cytotoxic activity of orally administered ITCs is derived from free forms cleaved from conjugated metabolite(s) in urine.

Acetylcysteine↗