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S Fukushima

Publications and source records attributed to S Fukushima.

At least 163 records · Page 9Linked to original sources
PubMed1997

Carcinogenicity of methylurea or morpholine in combination with sodium nitrite in rat multi-organ carcinogenesis bioassay.

For carcinogenic risk assessment of combinations of N-nitroso precursors in man, the effects of feeding methylurea (MU) or morpholine (Mor) plus sodium nitrite (NaNO2) were investigated using a multi-organ carcinogenesis model. In experiment 1, to initiate multiple organs, groups of 10 or 20 male F344 rats were treated with 6 carcinogens targeting different organs. Starting a week after completion of this initiation phase, animals were given 0.1% MU or 0.5% Mor in their food and/or 0.15% NaNO2 in their drinking water for 23 weeks. The induction of tumors and/or preneoplastic lesions in the forestomach and esophagus was significantly increased in the group receiving MU plus NaNO2. The numbers and areas of liver glutathione S-transferase placental form (GST-P)-positive foci were significantly elevated with MU or Mor plus NaNO2. Experiment 2 was conducted to assess formation of N-nitroso compounds in the stomach, and to detect DNA adduct generation in target organs by immunohistochemical staining. Groups of 5 or 14 animals were starved overnight, then given 0.4% MU or 2.0% Mor in the diet, or basal diet alone for 1 h. Then NaNO2 or distilled water was given intragastrically. The mean gastric N-methyl-N-nitrosourea yield in the MU plus NaNO2 group was 7700 micrograms at 2 h after combined administration. The mean N-nitrosomorpholine yield in the group given Mor plus NaNO2 was 6720 micrograms. Immunohistochemically, N7-methyldeoxyguanosine-positive nuclei were evident in the forestomach epithelium at 8 h after the combination treatment with MU plus NaNO2.

Administration, Oral↗
PubMed1997

High frequency of K-ras mutations in human colorectal hyperplastic polyps.

BACKGROUND: Hyperplastic polyps are common benign colorectal polyps, and are thought to have little association with malignant tumours in the colorectum. However, several reports suggest that some hyperplastic polyps may develop into colorectal neoplasms. AIM: To clarify genetic alterations in colorectal hyperplastic polyps. METHODS: Twenty eight colorectal polyps having serrated components were resected from patients endoscopically. The K-ras gene mutations in codons 12 and 13 were analysed by PCR-RFLP. Intranuclear p53 protein was immunostained by the avidin-biotin complex method. RESULTS: A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps. CONCLUSION: Some hyperplastic polyps may be true neoplastic lesions, and could be precursors of malignant neoplasia.

Adenoma↗
PubMed1997

Effect of thoracic irradiation on hepatocyte growth factor in rats lung and in bronchoalveolar lavage fluid of patients with thoracic malignancies.

This study aimed to examine the physiological role of hepatocyte growth factor (HGF) after thoracic irradiation. We analysed the changes of HGF protein levels in rat lung following 12 Gy of whole thoracic irradiation. Bronchoalveolar lavage fluid (BALF) was then collected from 11 patients (10 lung cancer and one oesophageal cancer) after completion of radiation therapy. One month after irradiation, the HGF protein level in the lungs of irradiated rats decreased (p<0.05), followed by a remarkable elevation in HGF protein levels 2 (p<0.05) and 3 months (nonsignificant) after irradiation accompanied by the clinical appearance of radiation pneumonitis. Finally, HGF protein levels in the lung returned to their original level 6 months after thoracic irradiation. In humans, HGF protein levels in the BALF in the limited irradiated area were lower than those obtained from unirradiated areas (p<0.05). In conclusion, hepatocyte growth factor production is transiently suppressed in the irradiated area after irradiation.

Aged↗
PubMed1997

[Clinical features of acute hepatitis G].

Fifty-one patients with acute A, B, C, and non A-C hepatitis were studied. Alcoholic abusers and drug-induced hepatitis were excluded from non A-C hepatitis. Among 10 patients with acute non A-C hepatitis, 3 were positive for HGV-RNA by nested RT-PCR as primer of 5' non-coding region of HGV. Maximal s-ALT values in acute hepatitis G patients were significantly higher than those in acute hepatitis C(p < 0.05), but not different from those in acute hepatitis A and B. Although HGV-RNA was demonstrated after 9 years of onset of hepatitis in one patient, non of three patients took chronic course. In one patient, route of transmission was assumed to be blood transfusion.

Acute Disease↗
PubMed1997

Cancer prevention by organosulfur compounds from garlic and onion.

Environmental compounds are known to be involved in both the generation and prevention of many human cancers. It is important to discover naturally occurring or synthetic compounds which can block the process of carcinogenesis. We have focused attention on several organosulfur compounds (OSCs) in garlic and onion, and analyzed their potential for chemoprevention in the post-initiation stage in a liver medium-term bioassay (Ito test) and a multi-organ carcinogenesis bioassay. In the ITO test, rats were given diethylnitrosamine (DEN), 200 mg/kg b.w., i.p.; starting 2 weeks later they were treated with test chemicals for 6 weeks and then killed. All rats were subjected to 2/3 hepatectomy 1 week after the start of test chemical treatment. Inhibitory effects of a number of compounds could be identified in terms of reduced numbers and areas of liver glutathione S-transferase placental (GST-P) positive foci. In the multi-organ carcinogenesis bioassay, rats were given DEN, N-methyl-N-nitrosourea, N-butyl-N-(4-hydroxybutyl)nitrosamine, N,N'-dimethylhydrazine, and dihydroxy-dipropylnitrosamine during the first 4 weeks, followed by test chemicals for 24 weeks. Various organs were examined. As a result, oil-soluble OSCs such as methyl propyl disulfide and propylene sulfide demonstrated inhibitory effects on the development of GST-P positive foci. Moreover, water-soluble OSCs such as S-methylcysteine and cysteine similarly decreased GST-P focus formation. In contrast, OSCs such as diallyl sulfide, diallyl trisulfide, and allyl methyl trisulfide enhanced formation of such altered hepatocellular foci. Inhibitory potential for colon and renal carcinogenesis was observed in rats treated with diallyl disulfide. Thus, the results indicate that some OSCs exert chemopreventive effects on chemical carcinogenesis. It must, however, be borne in mind that they may also demonstrate promotion potential, depending on the organ examined.

Animals↗
PubMed1996

Dose-related increases in quantitative values for altered hepatocytic foci and cytochrome P-450 levels in the livers of rats exposed to phenobarbital in a medium-term bioassay.

The dose-response relationship between liver tumor promoting activity and cytochrome P-450 (CYP) induction by phenobarbital sodium (PB) was investigated using the liver medium-term bioassay system of Ito. Two weeks after a single dose of N-nitrosodiethylamine (DEN) (200 mg/kg body weight, i.p.), rats were given PB at dietary levels of 500, 250, 125, 60, 30, 15 and 8 parts per million (ppm) for 6 weeks. All rats were subjected to partial hepatectomy at week 3, and were killed at week 8. Quantitative values for glutathione S-transferase placental form positive hepatocytic (GST-P+) foci were increased in the high dose groups dose-dependently. In contrast, the values in the low dose groups were rather lower than that of the control. CYP2B1, 2C6 and 3A2 were predominantly immunostainable in hepatocytes around the central vein. While Western blotting revealed CYP2B1 and 2C6 proteins to be increased with strict dose-dependence, CYP3A2 was only elevated at high doses. Thus, a good correlation between increase of GST-P+ foci and CYP3A2 induction was observed, as well as with CYP2B1 and 2C6 in high dose groups.

Animals↗
PubMed1996

p53 mutations in transitional cell carcinomas of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Involvement of p53 gene alterations has been demonstrated in a variety of human neoplasias including urinary bladder carcinomas. N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis models in rodents have been widely used to study carcinogenic processes in this organ. In the present study, transitional cell carcinomas induced in the urinary bladders of male F344 rats treated with 0.05% BBN for 16 or 32 weeks and then sacrificed at experimental week 32 were analyzed for mutational changes in the p53 and H-ras genes by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and subsequent DNA sequencing. The total p53 mutation incidences were 3/10 (30%) and 8/12 (66.7%) in rats treated with BBN for 16 weeks followed by 16 weeks' non-treatment, or in rats treated with BBN for 32 weeks, respectively, while the H-ras mutation incidences were 0/10 (0%), and 1/12 (8.3%), respectively. The present results indicate that mutations in the p53 gene might be involved in the process of urinary bladder carcinogenesis by BBN as part of a multistep pathway. However, considering the decreasing tendency in lesions with p53 mutations after stopping BBN administration, a p53 mutation alone would not appear to be sufficient to give a marked selective advantage to mutant cells. No evidence of H-ras mutation involvement was gained even for the late course of rat urinary bladder carcinogenesis.

Animals↗
PubMed1996

Immunohistochemically demonstrated variation in expression of cathepsin E between uracil-induced papillomatosis and N-butyl-N-(4-hydroxybutyl)nitrosamine-induced preneoplastic and neoplastic changes in rat urinary bladder.

Expression of rat urinary bladder cathepsin E in benign papillomatosis induced by uracil and various stages of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced carcinogenesis was investigated immunohistochemically. Seven-week-old, male F344/DuCrj rats were used. In the normal urothelium of control rats, cathepsin E stained in all layers of cells, although in umbrella cells and some basal cells the reaction was relatively weak. In rats given a diet containing 3% uracil for 5 weeks immunoreactivity of cathepsin E in uracil-induced papillomatosis was consistently homogeneous in all layers, but weaker than in normal urothelium. In rats given 0.05% BBN in drinking water for 12 weeks and subsequently maintained without treatment for 48 weeks cells with little cathepsin E, never observed in normal urothelium, appeared at 5 weeks above the basement membrane in the earliest stage of BBN-induced urinary bladder cancer (simple hyperplasia). Throughout the neoplastic process, groups of cells with a little cathepsin E were randomly distributed, with expression in the urothelium being markedly unstable. Almost all areas of squamous cell proliferation in TCC were negative for cathepsin E. Instability of cathepsin E expression in rat urothelium therefore appears characteristic for carcinogenesis and offers the possibility of using this feature as an early biomarker for urinary bladder carcinogenesis.

Animals↗
PubMed1996

Inhibitory effects of the dietary antioxidants butylated hydroxyanisole and butylated hydroxytoluene on bronchioloalveolar cell proliferation during the bleomycin-induced pulmonary fibrosing process in hamsters.

The effects of dietary antioxidants on bleomycin (BLM)-induced pulmonary fibrosis were investigated in Syrian golden hamsters. In addition, the influence on cell proliferative activity in bronchioloalveolar hyperplastic lesions during the lung fibrosing process was evaluated in terms of argyrophil nucleolar organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA). Male 6-wk-old hamsters were divided into six groups. Groups 1-3 were intratracheally instilled with BLM at a dose of 2.5 U/kg body weight on days 0 and 14, and then given a diet supplemented with 1% butylated hydroxyanisole (BHA), or 1% butylated hydroxytoluene (BHT), or basal diet alone for the following 41 days. Groups 4-6 were given 1% BHA, 1% BHT or basal diet without BLM treatment for the same time period as that in those of groups 1-3. The mortality rate of animals in group 1 (BLM/BHA) (one in 20; 5%) was lower than in those of groups 2 (BLM/BHT) (three in 20; 15%) and 3 (BLM alone) (four in 20; 20%). BHA and BHT treatments significantly inhibited lung weight gains by BLM (P < 0.05). Histopathologically, both BHA and BHT reduced BLM-induced pulmonary histopathological changes such as fibrosis, macrophage aggregation and epithelial proliferation, with a tendency for correlation with accumulation of type III collagen. In addition, antioxidant treatment significantly lowered the mean numbers of AgNORs (P < 0.01) and PCNA-labelling indices (P < 0.05) in the hyperplastic bronchioloalveolar lesions. The results thus indicate that these antioxidants exert inhibitory effects on proliferation of hyperplastic lesions associated with lung fibrosis.

Animals↗
PubMed1996

A nitric oxide-sensitive electrode: requirement of lower oxygen concentration for detecting nitric oxide from the tissue.

In order to directly detect nitric oxide (NO) liberated from isolated tissue, a practical and convenient method using a nitric oxide-sensitive electrode is described. To avoid the nonselective signal caused by ionic substances, the electrode was covered with three layers but remains permeable for gaseous substances. In a solution bubbled with 20% oxygen (pO2, approximately 150 mm Hg), administration of S-nitroso-N-acetyl-d, l-penicillamine (SNAP) at concentrations greater than 10(-7) mol/L elicited an electrode response. Based on a comparison with the chemical determination of NO released from SNAP, the electrode may be able to detect nitric oxide around nmol/L. At least 30 nmol NO per liter in anoxic conditions was reported to be detected by this electrode (Matsui, 1995). In a specially designed small chamber, the electrode was attached on the surface of endothelial side of the isolated aorta of the guinea pig. When carbachol was added to the chamber, the electrode responded when the solution was bubbled with 20% but not with 40% or 95% of oxygen, suggesting a much faster decomposition of nitric oxide in the presence of higher concentrations of oxygen. The electrode response to carbachol was abolished in the presence of NG-monomethyl-L-arginine or nitro arginine. These results suggest that the electrode method described in this manuscript is suitable for detecting nitric oxide liberated from isolated tissues when comparatively low oxygen levels are present in the physiological salt solution.

Animals↗
PubMed1996

Evaluating the significance of HLA class II genotype matching in living-related liver transplantation.

To evaluate the clinical significance of HLA class II matching in living-related liver transplantation, the genotypes of HLA class II including DPB1 were determined by the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method and their matching was compared to the postoperative course. Conventional serotypes included 15.6% and 13.6% errors in DR and DQ, respectively. Among 42 consecutive cases that were followed up over 1 year after transplant, rejection occurred in seven cases. There was no correlation between the matching for each locus and the frequency of rejection episodes. In this study, rejection-free cases were investigated in terms of the potency of immunosuppressive therapy and graft function during 1 year after operation. The doses of tacrolimus in unmatched cases tended to be larger than those in matched cases for every locus except for DQA1. Its trough levels in matched cases were lower than those in unmatched cases, especially at 9-12 months after operation for DRB1 (p < 0.05). The termination of steroid administration tended to be postponed in unmatched cases for every locus. Serum levels of asparatan transaminase, alanine transaminase gamma-glutamyltranspeptidase (gamma-GTP) and total bilirubin were generally lower in matched cases than in unmatched ones for DRB1, DQB1 and DPB1, while in DQA1 the tendency was the opposite, especially total bilirubin and gamma-GTP, which were p < 0.02 and p < 0.05, respectively, at 6 months after operation. Investigation of subclinical immune responses other than rejection episodes showed that DRB1, DQB1 and DPB1 matching had a beneficial effect on graft function, while DQA1 matching seemed to have a varied effect.

Child↗
PubMed1996

Promoting effects of dimethylarsinic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in rats.

Arsenicals are epidemiologically significant chemicals in relation to induction of urinary bladder cancer in man. In the present study, we investigated the dose-dependent promotion potential of dimethylarsinic acid (DMA), a major metabolite of inorganic arsenicals in mammals, for rat urinary bladder carcinogenesis. In experiment 1, 6-week-old male F344 rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks and then given one of several concentrations of DMA in their drinking water (groups 1-6: 0, 2, 10, 25, 50 and 100 p.p.m.) for 32 weeks. The development of preneoplastic lesions and tumors (papillomas and carcinomas) in the urinary bladder was enhanced by treatment with DMA in a dose-dependent manner. A significant increase in multiplicity of tumors (papillomas and carcinomas) was observed even at a low concentration of DMA (10 p.p.m.). On the other hand, no preneoplastic lesions and tumors were observed in the rats treated with DMA alone. In experiment 2, different concentrations of DMA (groups 1-4: 0, 10, 25 and 100 p.p.m.) in drinking water were administered to the rats for 8 weeks without prior initiation by BBN. A significant increase in the 5-bromo-2'-deoxyuridine labeling index and alteration of the surfaces of the urinary bladder epithelial cells, as revealed by scanning electron microscopy, provided evidence of a dose-dependent increase in cell proliferation due to the DMA treatment. These results suggest that DMA has the potential to promote rat urinary bladder carcinogenesis and one of the mechanisms involved is its stimulation of cell proliferation in the urinary bladder epithelium.

Animals↗
PubMed1996

Ender nailing for unstable surgical neck fractures of the humerus in elderly patients.

The purpose of this study was to assess the effects of stabilization of displaced and unstable surgical neck fractures of the humerus by Ender nailing followed by protected passive range of motion exercise of the shoulder. Thirty-four patients (29 women and 5 men) with such fractures were treated. The average age of patients was 69.5 years (range, 48-86 years), and the average followup period was 9.9 months (range, 6-22 months). Protected passive range of motion of the shoulder was started in 2 weeks after surgery for 25 patients and in 3 to 4 weeks for 9 patients. All patients experienced pain relief immediately after surgery. Bone union occurred at 5.9 weeks (range, 4-10 weeks) in all but 1 patient. The average range of motion of the shoulder at followup was 129.7 degrees elevation and 43.2 degrees external rotation. The average limitation of elbow extension was 4.3 degrees. The most important points of this procedure are to obtain immediate relief of pain, to stabilize the unstable fragment, and to begin protected passive range of motion of the shoulder before extensive adhesions develop.

Aged↗
PubMed1996

Immunohistochemical study of mixed tumor of the skin with marked ossification.

We observed an unusual case of mixed tumor of the skin associated with marked ossification on the upper lip of a 68-year-old Japanese woman. The tumor was a well-circumscribed mass that measured 3 x 3 x 2 cm and contained exuberant bone formation with a marrow-like structure. Histological examination of the tumor showed that the bones occupied a quarter of the specimen. Except for the large bone formation, the tumor showed typical features of a tubulocystic type of mixed tumor. The bone was formed without intervening cartilage, suggesting the possibility of the direct deposition of osteoid by metaplastic cells. To our knowledge, no similar case of mixed tumor of the skin associated with marked bone formation has been reported.

Adenoma, Pleomorphic↗
PubMed1996

Apoptosis of human embryonal carcinoma cells with in vitro differentiation.

An in vitro model of apoptosis and differentiation in human embryonal carcinoma (EC) cells was developed to study the mode of cell death and mechanisms of cell death in early development. Death of these cells was induced by treatment with retinoic acid (RA) under the same conditions as those for induction of differentiation. The manner of this cell death was apoptosis, not necrosis, with the morphological criterion for apoptosis. serum deprivation likewise caused apoptosis in both undifferentiated and differentiated EC cells. In differentiated EC cells, DNA fragmentation was observed in a smear pattern lacking the ladder pattern typically associated with apoptosis. However, in differentiated EC cells, DNA fragmentation occurred in various sizes. The expression of a carbohydrate antigen, LeY, a reported marker of apoptotic cancer cells, was increased by the treatment with RA. However, two-color analysis by flow cytometry with nick end labelling method revealed that LeY expression was closely correlated with cellular differentiation but not apoptosis after RA treatment in the human EC cell system. Collection of LeY positive cells by the magnetic bead method demonstrated that this expression was not due to apoptosis but rather to differentiation. On the other hand, LeY expression associated with apoptosis was induced by serum deprivation in both undifferentiated and differentiated EC cells. These results show that a subpopulation of undifferentiated EC cells takes the apoptotic pathway by induction of differentiation. The results also suggest that the population of cells taking an apoptotic pathway differs from a population of cells taking a differentiation pathway. This in vitro system for apoptosis in human EC cells will be useful for studies concerning apoptosis or programmed cell death in human developmental biology.

Apoptosis↗
PubMed1996

Acyclothymidine alleviates intestinal toxicity of 5'-deoxy-5-fluorouridine without loss of antitumor activity in mice.

To reduce the intestinal toxicity of orally administered 5'-deoxy-5-fluorouridine (5'-DFUR) in mice, we co-administered 5'-DFUR with acyclothymidine [AcyT, 5-methyl-(2'-hydroxyethoxymethyl) uracil], a potent inhibitor of pyrimidine nucleoside phosphorylase (PyNPase). Orally administered 5'-DFUR alone caused intestinal toxicity and severe damage to the intestinal villi, while 5'-DFUR with AcyT reduced the intestinal toxicity, and prevented damage to the intestinal villi. This toxicity arising from orally administered 5'-DFUR could not be reduced by intravenous administration of AcyT, but was alleviated by oral administration. Orally co-administered AcyT showed little effect on antitumor activity of 5'-DFUR toward subcutaneously implanted Lewis lung carcinoma, though the intestinal toxicity was reduced in the tumor-bearing mice. This finding suggests that orally co-administered AcyT may prevent the undesirable conversion of 5'-DFUR to 5-FU by PyNPase during the process of absorption in the intestinal tract.

Administration, Oral↗
PubMed1996

Modulation of the pharmacokinetics of 5'-deoxy-5-fluorouridine and 5-fluorouracil in rats by oral co-administration of acyclothymidine.

The effect of an inhibitor of pyrimidine nucleoside phosphorylase (PyNPase), acyclothymidine (AcyT), on the pharmacokinetics of 5'-deoxy-5-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU) was investigated in an oral co-administration of 5'-DFUR and AcyT in rats. AcyT increased the maximal plasma concentration (Cmax) and apparent absorption rate constant (ka) of 5'-DFUR, as expected, but the increase in AUC (area under the curve) was not significant. It was expected that AcyT would only inhibit the phosphorolytic degradation of 5'-DFUR to 5-FU, but the effect was more evident on the pharmacokinetic parameters of 5-FU than on those of 5'-DFUR. AcyT also increased AUC and Cmax of 5-FU when orally co-administered with 5-FU. An inhibitory effect of AcyT on the enzymatic degradation of 5-FU in rat liver and intestinal extract was investigated. AcyT inhibited the degradation in intestinal extract but not in the liver. The result suggests that orally administered AcyT affects the pharmacokinetics of 5-FU partly by inhibiting 5-FU degradation in the process of intestinal absorption as well as by acting as an inhibitor of PyNPase.

Administration, Oral↗