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Biomedical subjects

K Toyoda

Publications and source records attributed to K Toyoda.

At least 199 records · Page 11Linked to original sources

Immunocytochemical demonstration of Chlamydia infection in the urogenital tracts.

The peroxidase-antiperoxidase (PAP) technique was applied in cellular samples for the detection of chlamydial infection. Urethral scrapings were obtained from 316 males with clinically suspected urethritis. Positive PAP staining was detected in 118 (37%) of 316 tested. Cellular samples from the endocervix of 25 (54%) of 46 female contacts of males with positive Chlamydia-infected cells had positive Chlamydia-PAP staining. Chlamydia was also found in 12 (25%) of 48 male with gonorrhea. Serum IgG antibodies against Chlamydia trachomatis were evaluated using an enzyme-linked immunosorbent assay. A total of 29 out of 73 patients had positive Chlamydia serology; of these, 21 were positive for PAP staining, and eight were negative. The determination of Chlamydia antigen by means of the PAP technique appears to be a satisfactory method for detecting Chlamydia in male and female genital specimens; also, the procedure can be done readily in most laboratory settings.

Adolescent↗

Long-term in vivo carcinogenicity study of phenytoin (5,5-diphenylhydantoin) in F344 rats.

The carcinogenicity of phenytoin was studied in F344/DuCrj rats. Phenytoin was mixed with powdered basal diet at levels of 0 (control), 0.025 or 0.05% and groups of 50 male and 50 female rats were administered these doses ad lib. for 2 yr. Survival of the treated male and female rats was similar to that of the corresponding controls. There was a dose-related decrease in mean body weight of treated female rats, but body weights of treated male rats were similar to those of controls. A variety of tumours developed in all groups including the control group, but all of the neoplasms that were observed were histologically similar to known spontaneous tumours in this strain of rats and no statistically significant increase in the incidence of any particular tumour type was evident in the treated groups of either sex. Nor was there any evidence of accelerated tumour induction in any phenytoin-treated group. Thus, it is concluded that under the conditions used in this experiment phenytoin had no carcinogenic potential in F344 rats.

Animals↗

Initiating potential of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and 3,3',4',5,7-pentahydroxyflavone (quercetin) in two-stage mouse skin carcinogenesis.

Tumor initiating activity of 3,3',4',5,7-pentahydroxyflavone (quercetin), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and 2-(2-furyl)-3-(5-nitro-2-furyl) (AF-2) acrylamide) were tested in a two-stage mouse skin carcinogenesis model using 12-O-tetradecanoyl phorbol-13-acetate (TPA) as a promoter. These compounds dissolved in dimethyl sulfoxide were topically applied twice weekly for 5 weeks on the dorsal skin, and then followed by TPA for 47 weeks. The total initiating dose was 100 mg for each compound. 7,12-Dimethylbenz(a)anthracene (DMBA) at a total dose of 100 micrograms was used as a positive control compound. AF-2 induced skin tumors in 35% of the mice (average of 0.4 tumors/mouse), HBA in 15% in (0.2/mouse), BHT in 13% (0.13/mouse) and quercetin in 5% (0.1/mouse). No tumors appeared in the groups treated with either test chemicals alone or TPA alone. Statistical analysis according to either Fisher's exact test or Peto's trend test revealed significant differences for tumor appearance in the AF-2/TPA and BHA/TPA followed by TPA groups as compared to in the DMSO/TPA group. The results indicate that AF-2 and BHA have weak tumor initiating activity on mouse skin, but such effects are not apparent for BHT or quercetin.

Animals↗

Mammary and renal tumor induction by low doses of adriamycin in Sprague-Dawley rats.

The oncogenic potential of adriamycin was studied in both sexes of Sprague-Dawley rats. Single i.v. injection of 10 or 2 mg and repeated injections of 2 mg of adriamycin/kg body wt within 2 weeks were performed on rats, 50 days old at the commencement. All surviving animals were killed at 52 weeks of the experiment. Multiple mammary tumors, mostly fibroadenomas, were observed in 30 and 41% of the females given single low (2 mg/kg) or repeated doses (5 X 2 mg/kg) respectively. These incidences were significantly higher than those for the corresponding control group (8%). Two male rats in the low dose group also developed mammary tumors. Both sexes receiving the single high dose (10 mg/kg) injection demonstrated early mortality due to marked toxicity. The mortality of five repeated-treatment group was lower than a single high-dose group. Renal cell tumors were evident in five rats of the single, low dose groups and dysplastic foci of renal tubular epithelium occurred in the groups given a single low or repeated doses of adriamycin. Thus the present experiment provides preliminary indication of carcinogenic potential of this chemotherapeutic agent for both kidney and mammary gland of Sprague-Dawley rats and further investigations are necessary to evaluate the carcinogenic risk of adriamycin treatment.

Adenocarcinoma↗

Initiating activity in a two-stage mouse skin model of nine mutagenic pyrolysates of amino acids, soybean globulin and proteinaceous food.

Trp-P-1, Trp-P-2, MeA alpha C, A alpha C, Glu-P-1, Glu-P-2, Lys-P-1, IQ and Phe-P-1 were tested for tumour initiating activity in a two-stage skin carcinogenesis model using 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The total initiating doses were 20 mg for Trp-P-1, Trp-P-2, Glu-P-1 and Glu-P-2, 40 mg for MeA alpha C and A alpha C, 5 mg for Lys-P-1, 7.5 mg for IQ and 100 mg for Phe-P-1. 7,12-Dimethylbenz[a]anthracene was used as a positive control compound at a total dose of 100 micrograms. All compounds were topically applied twice weekly for 5 weeks on the dorsal skin, and then followed by similar TPA administration for 47 weeks. Trp-P-2 induced skin tumours in 30% of the mice (0.35 tumours/mouse), and Trp-P-1, MeA alpha C and Phe-P-1 in 10-20% (0.20-0.25 tumours/mouse). The smaller amounts of Lys-P-1 and IQ applied induced tumours at an incidence of 10 and 5% respectively. No tumours appeared in the groups treated with test chemicals alone or TPA alone. Statistical analysis according to either the Fisher exact test or Peto trend test revealed significant differences for tumour appearance in the Trp-P-1, Trp-P-2, MeA alpha C and Phe-P-1 followed by TPA groups as compared with that given TPA alone. The data were used to generate ID50 (50% initiating dose) values for each of the compounds.

Animals↗

Effect of a stable prostacyclin analogue on canine renal allograft rejection.

The effect of OP-41483 (Ono Pharmaceutical Co., Osaka, Japan), a stable prostacyclin analogue, on canine renal allograft rejection was investigated. Administration for 4 days after transplantation significantly increased renal cortical blood flow and urine output when compared with untreated dogs with renal allografts. Serum creatinine levels remained relatively low during postoperative days 1-4. Mean animal survival time was prolonged. Vascular lesions and mononuclear cell infiltration were greatly diminished in biopsy specimens removed on day 4. This stable prostacyclin analogue provided a degree of protection against canine renal allograft rejection.

Animals↗

Histochemical demonstration of colonic type mucin in glandular metaplasia and adenocarcinoma of the human urinary bladder.

Mucin in normal, metaplastic and neoplastic tissue specimens of the human urinary bladder was examined histochemically by the periodic acid-borohydride/potassium hydroxide/periodic acid-Schiff (PB/KOH/PAS) reaction and paradoxical concanavalin A (Con A) staining, both of which have been reported to detect mucins that are specific for the lower gastrointestinal tract. Normal mucosa, Brunn's nest, squamous metaplasia, transitional cell carcinoma, and squamous cell carcinoma produced only small amount of mucin and were negative for both PB/KOH/PAS and labile class III by Con A staining. However, several sections of mucin-producing metaplastic bladder lesions and many samples of adenocarcinoma arising from vesical mucosa and urachus contained PB/KOH/PAS-positive and/or labile class III mucin. Thus the colonic type mucin appeared in some materials of both benign and malignant mucin-producing lesions of the urinary bladder. The findings would be related to the embryogenesis of this organ.

Adenocarcinoma↗

Enhancing effect of cysteamine hydrochloride on the development of gastroduodenal tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine in F344 rats.

The effect of the duodenal ulceration induced by cysteamine hydrochloride on the development of gastroduodenal tumors initiated by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in F344 rats of both sexes. Cysteamine (200 mg/kg body wt.) was administered by gastric intubation at various times, before, during or after a 16 week period of MNNG (100 mg/liter in drinking water) treatment. In the preliminary experiment, while the ulcers induced were confined to the proximal duodenum, the pyloric region of the stomach also showed slight erosion. Five of 25 male rats given cysteamine 2 weeks before the start of MNNG treatment developed adenocarcinoma in the duodenum as compared to 1 case in the MNNG alone group. In addition, animals of both sexes which received cysteamine during MNNG treatment yielded significantly increased incidences of adenocarcinoma in the pyloric area of the stomach. In line with earlier reports, the present findings suggest that mucosal damage and subsequent regeneration or proliferation of mucosa are important co-factors for MNNG-induced gastroduodenal carcinogenesis in rats.

Adenocarcinoma↗

[Cytodiagnosis of Chlamydia trachomatis by the immunoperoxidase technic].

The PAP-immunocytochemistry using a monoclonal antibody against Chlamydia trachomatis was applied to male patients with clinically manifest urethritis and their female sex partners. In addition, serum levels of the antibody were determined by means of an ELISA system. Immunoperoxidase reactions were recognized on urethral scrapes in 53 (33%) out of 160 cases, and on endocervical specimens in 13 (59%) out of 22 sex partners of PAP-positive patients. In patients with gonococcal urethritis, an infection of C. trachomatis was revealed immunocytochemically in 11 (31%) out of 36 cases, and in 29 (46%) out of 62 cases with non-gonococcal urethritis. Following medication with 200 mg of minocycline or doxycycline per day, PAP staining became negative in 23 (66%) out of 35 cases. The levels of serum antibody against C. trachomatis were undetectable in 8 (26%) out of 29 PAP-positive cases, but positive in 7 (15%) out of 44 PAP-negative cases.

Adult↗

[Combination chemotherapy of cyclophosphamide, adriamycin and cisplatin in advanced urothelial cancer].

Sixteen patients with advanced evaluable urothelial cancer were treated with a chemotherapy regimen of cyclophosphamide, adriamycin and cisplatin (CAP). Cisplatin 50 mg/m2 and adriamycin 30 mg/m2 were given on the first day and cyclophosphamide 200 mg/m2 was given from the second to the fifth day. This course was repeated every 3 weeks. The objective response rate was 25% (4 of 16 patients), with 1 patient achieving complete remission. The survival time of responders was longer than that of nonresponders, although the difference was not significant (generalized Wilcoxon method). As side effects, nausea with vomiting (43.8%), renal dysfunction (6.3%), anemia (12.5%), leucopenia (12.5%), thrombocytopenia (25.0%), alopecia (68.8%), heart failure (6.3%) and peripheral neuropathy (6.3%) were noticed. One patient died of sepsis due to agranulocytosis and another died suddenly of heart failure.

Adult↗

Human leucocyte antigen and coronary artery spasm.

To elucidate possible genetic links in the pathogenesis of coronary artery spasm, we investigated the frequencies of human leucocyte antigen in 37 patients with variant angina and 236 unrelated healthy controls. We found no significant differences in human leucocyte antigen frequencies between the patients and the controls. These results may suggest that genetic factors in linkage disequilibrium with human leucocyte antigen may not be involved in the pathogenesis of coronary artery spasm.

Angina Pectoris, Variant↗

Carcinogenicity study of sodium hypochlorite in F344 rats.

The carcinogenic potential of sodium hypochlorite was examined in F344 rats. Groups of 50 males or 50 females were given sodium hypochlorite in their drinking-water, at concentrations of 0.1 and 0.05% for males and 0.2 and 0.1% for females, for 104 wk. Similar numbers of male and female rats received distilled water without supplement throughout the experiment. All surviving rats were killed at wk 112 (after 8 wk on untreated tap-water). Rats of both sexes given the chemical showed a reduction in body-weight gain, but haematological and biochemical examination of the blood showed no changes due to treatment, and no significant lesions attributable to the treatment were detected in any tissue in the histopathological investigation. Although a variety of tumours developed in all groups, no dose-related change in either the incidence or latent period of tumours was observed for any organ or tissue in either sex. Under the experimental conditions described, therefore, sodium hypochlorite was not carcinogenic in F344 rats.

Animals↗