Biomedical subjects

S Fukushima

Publications and source records attributed to S Fukushima.

At least 235 records · Page 13Linked to original sources

PubMed1993

Prophylactic oral UFT therapy for superficial bladder cancer.

BACKGROUND: A randomized prospective trial was performed to determine whether long-term oral UFT (a 1:4 mixture of tegafur and uracil) (Taiho Pharmaceutical Co., Tokyo, Japan) therapy was effective in preventing the intravesical recurrence of superficial bladder cancer. METHODS: A total of 112 patients with newly diagnosed superficial transitional cell carcinoma of bladder (Ta, T1 and G1 or G2) were randomized into a UFT-treated group (300-400 mg/d for 2 years) and a control group. RESULTS: After a median follow-up period of 24.5 months, the recurrence rate was 25.7% for the UFT group and 43.3% for the control group (P = 0.015, log-rank test). Side effects of UFT administration were acceptably low. CONCLUSIONS: These results suggest that long-term UFT administration after transurethral resection is effective in preventing the recurrence of superficial bladder cancer.

Administration, Oral↗

PubMed1993

Effects of sodium nitrite and catechol, 3-methoxycatechol, or butylated hydroxyanisole in combination in a rat multiorgan carcinogenesis model.

Effects of simultaneous treatment with NaNO2 and butylated hydroxyanisole, catechol, or 3-methoxycatechol were examined in a rat multiorgan carcinogenesis model. Groups of 15 animals were given a single i.p. injection of 100 mg/kg of body weight diethylnitrosamine, 4 i.p. injections of 20 mg/kg of body weight N-methylnitrosourea, 4 s.c. injections of 40 mg/kg of body weight dimethylhydrazine, p.o. treatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for the first 2 weeks and p.o. treatment with 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine in the drinking water for the next 2 weeks of the initial 4-week initiation period. Starting 3 days after the completion of these carcinogen treatments, animals were given diets containing 2% butylated hydroxyanisole, 0.8% catechol, 2% 3-methoxycatechol, or basal diet either alone or in combination with 0.3% sodium nitrite until week 28, when complete autopsy was performed. Histological examination showed that NaNO2 strongly enhanced development of forestomach lesions but inhibited that of glandular stomach lesions in rats simultaneously given catechol or 3-methoxycatechol with or without prior carcinogen exposure. 3-Methoxycatechol promoted esophageal carcinogenesis either with or without NaNO2, but promoting effects of catechol were evident only in the presence of NaNO2. In addition, treatment with NaNO2 after carcinogen exposure enhanced forestomach carcinogenesis. These results indicate that NaNO2 can modify phenolic antioxidant-induced cell proliferation and/or carcinogenesis, particularly in the upper digestive tract.

Animals↗

PubMed1993

Disposition of enantiomers of sulpiride in humans and rats.

Pharmacokinetics of sulpiride enantiomers after intravenous administration of (+/-)-, (+)-, and (-)-sulpiride was examined in humans and rats. Pharmacokinetics profiles were similar in (+)- and (-)-enantiomers after intravenous administration of (+/-)-sulpiride. Metabolic inversion at a chiral centre was not observed after intravenous administration of each enantiomer in rats.

Administration, Oral↗

PubMed1993

Inhibitory effects of procainamide and probenecid on renal excretion of sultopride enantiomers in rats.

The effects of the coadministration of procainamide and probenecid on the pharmacokinetic behavior of sultopride, an antipsychotic agent, after intravenous administration were studied with rats. The areas under the concentration-time curve for and renal clearances of (+)-sultopride and (-)-sultopride, which exist as organic cations under physiological pH conditions, were significantly decreased (p < 0.01) by the coadministration of procainamide, an organic cation under physiological pH conditions. The renal clearance of (-)-sultopride was partially decreased (p < 0.05) by the coadministration of probenecid, an organic anion under physiological pH conditions. The results suggest that drug-drug interactions between organic cations and organic anions occur to a certain extent during the tubular secretion process in rats.

Amisulpride↗

PubMed1993

Lack of promotion of N-butyl-N-(4-hydroxybutyl)nitrosamine-initiated urinary bladder carcinogenesis in mice by rat cancer promoters.

The effects of dietary exposure to sodium L-ascorbate (Na-AsA), butylated hydroxyanisole (BHA), and diphenyl on the development of urinary bladder tumors in a mouse two-stage carcinogenesis model were examined. Male B6C3F1 mice received 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in the drinking water for 4 weeks and were then treated with 5% Na-AsA, 1% BHA, or 1% diphenyl for 32 weeks. None of these chemicals enhanced the development of either preneoplastic or neoplastic lesions in the urinary bladder. Furthermore, DNA synthesis levels of urinary bladder epithelium in mice treated with each substance alone for 8 weeks were not elevated significantly, although Na-AsA was associated with a significant increase in the urinary pH value and Na+ concentration. The results indicate that Na-AsA, BHA, and diphenyl do not exert an enhancing influence on mouse bladder carcinogenesis, in clear contrast to the case in the rat.

Animals↗

PubMed1993

Modifying influence of prior treatment with toxic agents on induction of preneoplastic and neoplastic lesions in a medium-term multi-organ carcinogenesis bioassay.

The modifying potential of prior administration of toxic agents was investigated in our multi-organ carcinogenesis model using male F344/DuCrj rats with the aim of assessing the link between tissue damage and initiation. Animals were administered one of four toxic agents for 8 wk, and then treated with N-diethylnitrosamine (DEN, 100 mg/kg body weight (b.w.), intraperitoneally (i.p.), single injection), N-methylnitrosourea (MNU, 20 mg/kg b.w., i.p., four times during wk 9 and 10), and dihydroxy-di-N-propylnitrosamine (DHPN, 0.1% in drinking water, during wk 11 and 12) for multi-organ carcinogenesis. All surviving rats were killed at the end of wk 36, and the major organs carefully examined for preneoplastic and neoplastic lesion development. Immunohistochemical demonstration of glutathione S-transferase placental form (GST-P) positive foci was also performed to facilitate quantitative assessment of liver lesion development. D-galactosamine (300 mg/kg b.w., i.p., once a week), a hepatotoxin, significantly inhibited the induction of GST-P positive foci, while 4,4'-diaminodiphenylmethane (DDPM, 0.1% in diet), a bile duct proliferator which is itself a hepatocarcinogen, possessed enhancing activity. DDPM, also a goitrogen, clearly inhibited the development of follicular cell tumors in the thyroid. Uracil (3.0% in diet), which is an inducer of papillomatosis in the urinary bladder, did not exert any enhancing potential on bladder carcinogenesis. Bleomycin (2 mg/kg b.w., i.p., twice a week), which is an alveolar epithelium injuring agent, also did not modify the induction of alveolar epithelium proliferative lesions. These results indicate that prior organ injury by toxic agents does not always act to enhance sensitivity to carcinogenesis.

Aniline Compounds↗

PubMed1993

Epithelia hyperplasia in the renal papilla and pelvis but not the urinary bladder of male F344 rats associated with dietary sodium phosphates after uracil exposure.

Effects of the bladder tumor promoter Na3PO4 and the non-bladder-tumor promoter NaH2PO4 on development of hyperplastic lesions of urinary bladder and renal papilla/pelvis were investigated after exposure of male F344 rats to the nongenotoxic carcinogen uracil. Animals were administered with 3.0% uracil in the diet for 4 weeks and thereafter fed 3.0% Na3PO4 or 3.0% NaH2PO4 for 32 weeks. No enhancing effect of either phosphate salt on uracil-induced proliferative lesions of urinary bladder was observed. However, the sequential treatments gave rise to enhanced development of hyperplastic lesions in the renal papilla/pelvis compared to the case with uracil alone. In addition, a small number of renal pelvic papillomas were observed in the group given Na3PO4 after uracil. These phosphate salts also induced nephrocalcinosis in the papilla/pelvis concomitant with development of renal hyperplastic lesions in this location. A sequential study revealed calculus formation and proliferative lesions in both the urinary bladder and renal papilla/pelvis after 4 weeks dietary application of uracil. After cessation, calculi disappeared and the majority of hyperplastic lesions regressed, consistent with a decrease in DNA synthesis levels. Persistence of uracil-induced epithelial hyperplasia in renal papilla/pelvis under the influence of phosphate salts might have been directly due to chronic stimulation by nephrocalcinosis in these sites.

Animals↗

PubMed1993

Renal lesions induced in F344/DuCrj rats by 4-weeks oral administration of dimethylarsinic acid.

The nephrotoxicity of dimethylarsinic acid (cacodylic acid, DMA) was examined in male and female F344/DuCrj rats. DMA administered perorally at doses of 113, 85, and 57 mg/kg for 4 weeks produced dose-related decreases in body weight and survival rate in both sexes. Mortality was higher and appeared more quickly in females than in males. Histopathological findings in the kidney were proximal tubular degeneration and necrosis, as well as papillary necrosis, and hyperplasia of the epithelium covering the papillae. Since extensive proximal tubular necrosis was observed only in dead animals of both sexes, and not in survivors or the controls, it was therefore concluded that the main cause of death could be attributed to nephrotoxicity of DMA. The results thus show that DMA is nephrotoxic to both male and female rats.

Administration, Oral↗

PubMed1993

Subchronic toxicity study of methyl hesperidin in mice.

A subchronic toxicity study of methyl hesperidin was performed using B6C3F1 mice. The flavonoid was administered to groups of ten males and ten females in dietary levels of 0, 0.3, 0.6, 1.25, 2.5 and 5.0% for 13 weeks. No significant treatment-related differences were found in data for body weights, food and water consumption, hematology, clinical chemistry and organ weights. Furthermore, no effects of treatment were observed on gross and histopathological examination of the major organs. The present experiment thus demonstrated that methyl hesperidin exerts no obvious toxic effects in mice of either sex when administered at a level as high as 5.0% in the diet.

Administration, Oral↗

PubMed1993

Ocular manifestations of adult T-cell leukemia/lymphoma. A clinicopathologic study.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a recently described distinct clinicopathologic entity characterized by an extremely aggressive clinical course, a leukemic or lymphomatous proliferation of hyperlobulated peripheral T cells, and an association with infection by a retrovirus, human T-lymphotropic virus type I (HTLV-I). The authors present a patient with ATLL who initially had clinical features of severe uniocular intraocular inflammation, simulating acute retinal necrosis or herpetic retinitis, but results of histopathologic examination of the globe showed ATLL. PATIENT: A 38-year-old man had severe unilateral intraocular inflammation associated with widespread diffuse retinitis. Two weeks later, a focal retinitis with vasculitis developed nasal to the optic disc in the opposite eye. Shortly thereafter, mental disturbance developed, and the patient died less than 3 months after onset of the ocular symptoms. RESULTS: Results of postmortem examination showed atypical lymphocytic infiltration in the eyes, brain, and other systemic organs. Results of histopathologic and immunohistochemical studies showed that the atypical cells infiltrating the ocular tissues were ATLL cells. CONCLUSIONS: Patients infected with HTLV-I initially can have intraocular T-cell lymphoma that simulates acute retinal necrosis or herpetic retinitis.

Adult↗

PubMed1993

No enhancing effects of calcium/magnesium salts of L-glutamate and L-ascorbate on tumor development in a rat medium-term multiorgan carcinogenesis bioassay.

Calcium/magnesium salts of L-glutamate and L-ascorbate were tested for modification potential using a rat multiorgan carcinogenesis bioassay. Following sequential treatment with three different carcinogens (diethylnitrosamine, N-methylnitrosourea, and dihydroxydi-N-propylnitrosamine) over a 4-wk period, rats were given diet containing 5% monocalcium di-L-glutamate tetrahydrate (Ca-glutamate), 2.5% monomagnesium di-L-glutamate tetrahydrate (Mg-glutamate), 5% L-glutamic acid, 5% monocalcium di-L-ascorbate dihydrate (Ca-ascorbate), 2.5% monomagnesium di-L-ascorbate dihydrate (Mg-ascorbate), or 5% L-ascorbic acid for 16 wk. Body weight increase was slightly suppressed in the groups receiving Ca-ascorbate, Mg-ascorbate, and ascorbic acid supplementation after the carcinogen treatments. While administration of Ca-glutamate or Ca-ascorbate raised urinary pH, ascorbic acid values were decreased. Concentrations of calcium and magnesium ions in the urine increased after ingestion of Ca-glutamate or Ca-ascorbate, and Mg-glutamate or Mg-ascorbate, respectively, but phosphorus levels decreased in all groups given calcium and magnesium salts. No consistent treatment-related changes in the concentrations of sodium or potassium ions in the urine were detected. Histopathological investigation at wk 20 did not demonstrate any modification of tumorigenesis with regard to the incidence of frequency of lesions developing in the various target organs/tissues. The present results thus revealed no apparent enhancement of carcinogenesis at any site, including the urinary system, by calcium or magnesium salts using the present rat multiorgan carcinogenesis bioassay.

Animals↗

PubMed1993

Severity of promotion by sodium salts of succinic acid in rat urinary bladder carcinogenesis correlates with sodium ion concentration under conditions of equal urinary pH.

Elevation of urinary pH and Na ion concentration induced by feeding high doses of sodium salts plays a crucial role in promotion of urinary bladder carcinogenesis in male rats initially treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In the present study, urinary bladder carcinogenesis in male F344 rats was promoted by feeding the mono- and di-sodium salts of succinic acid, and the activity was enhanced by varying urinary sodium ion concentration under conditions of equally high pH. In Experiment 1, the rats were given 0.05% BBN in their drinking water for 4 weeks and then fed basal diet containing 5% succinic acid, 5% sodium succinate (Na-Suc) or 5% di-sodium succinate (2Na-Suc) for 32 weeks. The development of carcinomas in the urinary bladder was enhanced by treatment with Na-Suc and with 2Na-Suc. 2Na-Suc induced larger urinary bladder tumors than the Na-Suc. In Experiment 2, 5% Na-Suc and/or 5% 2Na-Suc were fed to the rats for 8 weeks without prior BBN treatment. Induction of simple hyperplasia as observed by light microscopy, was greater in rats fed 2Na-Suc than Na-Suc. Increased 5-bromo-2'-deoxyuridine labeling index and alterations of the urothelial surface observed by scanning electron microscopy of the urinary bladder were similarly greater in rats fed 2Na-Suc compared to Na-Suc. In addition, there was a tendency toward increased spermidine/spermine N1-acetyltransferase activity in the urinary bladder epithelium of rats fed 5% 2Na-Suc. The results of Experiment 2 corresponded to differences in promoting activity for the different chemicals in Experiment 1. Thus, tumor growth was associated with sodium ion concentration level under conditions of equal increase of urinary pH.

Animals↗

PubMed1993

Carcinogenicity of catechol in F344 rats and B6C3F1 mice.

Carcinogenicity of catechol, a naturally occurring and industrial chemical which has been shown to have strong cell proliferating potential on rat glandular stomach epithelium, was investigated in male and female F344 rats and B6C3F1 mice. Groups of 30 male and female F344 rats and B6C3F1 mice were treated with 0.8% catechol in powdered diet continuously for 104 weeks (rats) or 96 weeks (mice). At necropsy, neoplastic lesions were observed mainly in the glandular stomach of both species. Adenomas were found in all rats and in the majority of mice: 29 out of 30 (97%) in males and 21 out of 29 (72%) females. In addition 15 out of 28 (54%) and 12 out of 28 (43%) of the male and female rats respectively, had well differentiated adenocarcinomas. No adenocarcinomas were found in mice of either sex. In the forestomach epithelium, although significant increase in papilloma development was not evident, incidences of squamous cell hyperplasia were significantly increased in rats and mice of both sexes. In other organs examined, incidence and numbers of liver hyperplastic foci per cm2 liver section were significantly lower in male rats. Although the incidence was not different, the numbers of hyperplastic foci were also significantly reduced in female rats. Thus the present experiment clearly demonstrated that catechol exerts carcinogenic activity in rodent glandular stomach epithelium.

Adenocarcinoma↗

PubMed1993

Influence of aging on multi-organ carcinogenesis in rats induced by N-methyl-N-nitrosourea.

The effects of aging on the multi-organ carcinogenesis induced in rats by N-methyl-N-nitrosourea (MNU), a direct carcinogen which does not need metabolic activation to exert carcinogenicity, were examined in male F344 rats. In the first experiment, rats at 6, 52, and 98 weeks of age were treated with MNU (20 mg/kg body weight, i.p.) twice weekly for 6 weeks and then maintained without any further treatment for 24 weeks in the case of young and middle-aged rats and for 18 weeks in the case of the old rats. In young rats, malignant lymphomas, particularly thymic types, were observed at significantly high incidence. A striking result in the middle-aged rats was the significantly higher incidence of adenocarcinomas in the small intestine than in young or old animals. The induction of proliferative and neoplastic lesions of the large intestine also tended to be increased in middle-aged rats. In addition, epithelial hyperplasia of the tongue, but not the forestomach, occurred at the highest incidence in the middle-aged group. There were no differences in the induction of epithelial lesions in the urinary bladder among the groups. In a second experiment, investigation of DNA synthesis in the tongue, small and large intestines, urinary bladder and lymph nodes did reveal significant increases or tendency for increase in the MNU-treated groups, but without differences with age. In contrast, the thymus of young rats showed significantly increased incorporation of BrdU label after administration of MNU, whereas it was markedly reduced in middle-aged rats. In a third experiment, O6-methyldeoxyguanine (O6-medG) DNA adduct formation was immunohistochemically detected in various organs including the thymus, forestomach, and small intestine without any differences with age. Thus, the results demonstrated that while the target organs of MNU are modified by the age of the animals, levels of DNA synthesis and O6-medG DNA adduct formation in most cases can not explain the observed differences in carcinogenic susceptibility.

Adenocarcinoma↗

PubMed1993

Correlation between medium-term multi-organ carcinogenesis bioassay data and long-term observation results in rats.

The effects of four test chemicals [2-acetylaminofluorene (2-AAF), D,L-ethionine (ethionine), butylated hydroxyanisole (BHA), and catechol] were compared in medium- and long-term in vivo systems. In the medium-term assay, animals were sequentially treated with N-diethylnitrosamine (100 mg/kg body weight, i.p., single injection), N-methylnitrosourea (20 mg/kg body weight, i.p., 4 times during weeks 1 and 2), N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water during weeks 1 and 2), 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times during weeks 3 and 4) and dihydroxy-di-N-propylnitrosamine (0.1% in the drinking water during weeks 3 and 4) for multi-organ initiation, and then treated with one of the four test chemicals for 24 weeks, and killed at week 28 (group 1). In the long-term assay, animals were treated in the same manner and then given basal diet and tap water (group 3) or test chemical continuously (group 4) for the remainder of the lifespan. Animals receiving multi-organ initiation and then maintained on basal diet for 24 weeks (group 2) or their lifespan (group 5) served as controls. Detailed histopathological examinations were performed on all rats. Hepatocellular carcinoma incidences in the long-term assay were found to reflect closely the respective medium-term results. Induction of proliferative forestomach or glandular stomach lesions by BHA and/or catechol, and bladder lesions by 2-AAF and BHA in the medium-term assay also correlated with tumor development in the long-term. Furthermore, inhibition of thyroid proliferative lesions by all test chemicals corresponded with low thyroid tumor incidences in the long-term assay. The observed strong correlation between medium- and long-term results confirms the applicability of our medium-term multi-organ carcinogenesis bioassay system for detection of modifying effects of test chemicals in different organs.

2-Acetylaminofluorene↗

PubMed1993

Localization of transglutaminase 1 mRNA in normal and psoriatic epidermis by non-radioactive in situ hybridization.

We examined the expression of the transglutaminase 1 (TGase 1) gene in frozen sections of normal and psoriatic epidermis by means of non-radioactive in situ hybridization with digoxigenin-labelled cRNA probes. TGase 1 mRNA was expressed in the granular layer of normal epidermis, regardless of ortho- or hyperkeratosis. However, in psoriatic epidermis, TGase 1 mRNA was detected in the suprabasal spinous layer, but not in the subcorneal layer. These results indicate that TGase 1 gene expression is limited to the last stage of keratinization in normal epidermis and this regulation is disturbed in psoriasis.

Adult↗

PubMed1993

Acetylcholine-induced endothelium-independent relaxations in monkey isolated superior and inferior caval veins.

1. We examined the effects of acetylcholine (ACh), isoprenaline (Isop) and Ca-ionophore, A23187 on monkey isolated superior (SCV) and inferior caval veins (ICV) with and without intact endothelium, which had been partially contracted by 2 x 10(-6)-5 x 10(-6) M prostaglandin F2 alpha (PGF2 alpha). 2. Low concentrations of ACh (10(-10)-10(-9) M) produced a dose-dependent relaxation in the precontracted venous segments with endothelium. ACh at concentrations more than 10(-7) M elicited a transient contraction followed by a relaxation in these segments. 3. An addition of 5 x 10(-7) M A 23187 induced about 60% of maximum relaxation produced by 10(-5) M sodium nitroprusside (SNP) in each venous segment with endothelium. 4. Isop (10(-10)-10(-5) M) caused a dose-related relaxation in the precontracted caval veins with intact endothelium. 5. Removal of endothelium caused no significant effect on the ACh-induced dual responses but a significant inhibition of the A23187-induced relaxation. 6. Pretreatment with atropine antagonized competitively the ACh-induced relaxations in the endothelium-intact and endothelium-denuded caval veins. The Schild plot analysis showed that the pA2 values of the segments with and without endothelium were 9.72 +/- 0.14 (n = 5) and 10.01 +/- 0.23 (n = 6) in the ICV; and 9.95 +/- 0.20 (n = 5) and 9.70 +/- 0.10 (n = 5) in the SCV, respectively. 7. Pretreatment with 5 x 10-5M aspirin, 3 x 10-5M N0-nitro-L-arginine methylester, 1 mM tetraethylammonium,or 3 x 10-6 M glibenclamide caused no significant effect on the basal tone, ACh induced transient contraction, and ACh;.induced relaxation in the precontracted venous segments with and without endothelium.8. Pretreatment with 10-5 M methylene blue produced a significant reduction of the ACh- and SNP induced relaxations in the precontracted venous segments with and without endothelium. The pretreatment with the same concentration of methylene blue, however, caused no significant effect on the Isop-induced relaxation in venous segments with endothelium.9. The results suggest that ACh acts directly on the venous smooth muscle cells via a high-affinity muscarinic receptor subtype to accumulate cellular cyclic GMP producing endothelium-independent relaxation in the monkey caval veins.

Acetylcholine↗

PubMed1993

Disposition of enantiomers of sultopride in a human, rats and rabbits.

Pharmacokinetics of sultopride enantiomers was examined following a single dose in a human, rabbits and rats. Pharmacokinetic profiles were similar between (+)- and (-)-enantiomers of sultopride in human, whereas the serum concentrations of (-)-sultopride were slightly higher than those of (+)-sultopride after i.v. administration of 50 mg/kg of racemic sultopride to rats and rabbits.

Amisulpride↗