Search PubMed⌕ Search

Biomedical subjects

N Ito

Publications and source records attributed to N Ito.

At least 379 records · Page 21Linked to original sources
PubMed1992

Histogenesis of human stomach cancers based on assessment of differentiation.

The histogenesis of human stomach cancer was assessed based on the determination of the differentiation of component cancer cells. Specimens of 229 surgically obtained primary gastric cancers were used. Histochemical staining of mucins [paradoxical concanavalin A, galactose oxidase-Schiff (GOS), and sialidase-GOS sequence] and immunohistochemical demonstration of pepsinogens (Pg) I and II allowed the differentiation of gastric elements including mucous neck cells, pyloric gland cells, and surface mucous cells as well as intestinal goblet and absorptive cell types. Of 122 papillary and tubular adenocarcinomas, the proportion consisting mainly of intestinal type cells increased with progression from 22.9% (early) to 41.9% (advanced). Similarly, intestinal features increased with progression from 8.3% (early) to 25.4% (advanced) in the 107 poorly differentiated adenocarcinomas, signet ring cell carcinomas, and mucinous adenocarcinomas studied. A phenotypic shift from gastric- to intestinal-type expression was thus observed with progression of each histologic type of gastric cancer. Furthermore, tumors consisting mainly of gastric-type cells were commonly found within intestinal metaplastic mucosa, suggesting that this latter is not a preneoplastic lesion for gastric cancers in humans.

Adult↗
PubMed1992

Suppression of diethylnitrosamine-initiated preneoplastic foci development in the rat liver by combined administration of four antioxidants at low doses.

Potential synergism between 4 antioxidants acting at low doses on development of glutathione S-transferase placental form (GST-P)-positive liver cell foci was examined in male rats initially given diethylnitrosamine (200 mg/kg, i.p.). Beginning 2 weeks after the initiation, rats received the antioxidants, individually or in combination, in the diet for 6 weeks. All rats were subjected to two-thirds partial hepatectomy at week 3 and killed at week 8. The numbers and areas of GST-P-positive foci were significantly decreased by single treatment with butylated hydroxyanisole (BHA, 1%), tert-butylhydroquinone (TBHQ, 1%) and catechol (0.8%), but not with sesamol (0.5%). Combined treatments (BHA + TBHQ, catechol + sesamol, or all 4 chemicals) at a quarter of the above dose levels resulted in decrease in numbers and areas of foci to levels less than the sums of individual inhibition data obtained with the one-quarter levels. Although these combined effects were not statistically significant in the additive model, the results indicate possible synergistic suppression of carcinogenesis by low-dose combined treatment with anti-cancer agents and the usefulness of the present protocol for this type of analysis.

Animals↗
PubMed1992

Elevated levels of plasma transforming growth factor-beta in patients with hepatocellular carcinoma.

We measured the plasma transforming growth factor-beta (TGF-beta) concentration in 14 patients with human hepatocellular carcinoma (HCC) and 9 age-matched normal subjects using growth inhibition assay of mink lung epithelial cells. The calculated plasma TGF-beta concentration in the patients with HCC was 28.6 +/- 27.9 ng/ml (mean +/- SE), showing significant elevation compared with that in 9 normal subjects (5.3 +/- 3.3 ng/ml, P less than 0.01). In three cases, we could measure plasma TGF-beta levels before and after their treatment for HCC. The plasma TGF-beta levels decreased from 59.0 to 18.2 ng/ml after hepatic resection in one case, and from 24.0 to 10.7 ng/ml and from 12.4 to 3.4 ng/ml after transhepatic arterial embolization in the other two cases. These data indicate that plasma TGF-beta level is elevated in patients with HCC, probably due to release from HCC tissues.

Animals↗
PubMed1992

Modifying effects of various chemicals on tumor development in a rat wide-spectrum organ carcinogenesis model.

The efficacy of a wide-spectrum organ carcinogenesis model for detection of modification potential of exogenous agents was investigated in F344 male rats. Groups of animals were sequentially injected with N-bis(2-hydroxypropyl)nitrosamine (1000 mg/kg body weight, i.p., in saline, twice in week 1), N-ethyl-N-hydroxyethylnitrosamine (1500 mg/kg body weight, i.g., in distilled water, twice in week 2) and 3,2'-dimethyl-4-aminobiphenyl (75 mg/kg body weight, s.c., in corn oil, twice in week 3) for wide-spectrum initiation of target organs and then given one of 10 test chemicals, comprising 6 hepatocarcinogens and 4 non-hepatocarcinogens, for 12 weeks. All 10 chemicals exerted modifying effects in their respective target organs. Enhancing influence could be detected in the liver and urinary bladder with 2-acetylaminofluorene, ethionine, and 3'-methyl-4-dimethylaminoazobenzene; in the liver and thyroid with 4,4'-diaminodiphenylmethane and phenobarbital; in the esophagus and urinary bladder with N-butyl-N-(4-hydroxybutyl)nitrosamine; in the forestomach and urinary bladder with butylated hydroxyanisole; in the liver with 7,12-dimethylbenz[a]anthracene and in the liver and lung with 3-methylcholanthrene. Inhibitory effects on development of glutathione S-transferase placental form-positive liver cell foci were observed with clofibrate. The results indicate that the present model can be reliably utilized as a whole body medium-term bioassay system for assessment of environmental cancer modifiers.

Animals↗
PubMed1992

Induction of adenocarcinomas in the glandular stomach of BALB/c mice treated with N-methyl-N-nitrosourea.

Male 6-week-old BALB/c strain animals (groups 1 and 2) received 10 weekly intragastric intubations of 0.5 mg/mouse of N-methyl-N-nitrosourea. At week 11 the forestomachs were resected in group 1 but not group 2. Although many animals in group 2 died due to development of squamous cell carcinomas in the forestomach, development of cancers in the glandular stomach was quite similar in both groups. Well-differentiated adenocarcinomas in groups 1 and 2 were found at low incidence at week 20, rising to 100% at week 40, with two lesions metastasizing to the lymph nodes. Four poorly differentiated adenocarcinomas and 5 signet ring cell carcinomas were also found in 27 glandular stomach tumor-bearing animals.

Adenocarcinoma↗
PubMed1992

Enhancing effects of harman and norharman on induction of preneoplastic and neoplastic kidney lesions in rats initiated with N-ethyl-N-hydroxyethylnitrosamine.

The modifying potential of two nephrotoxic agents, harman and norharman, on N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal and hepatic carcinogenesis was investigated in male F344/DuCrj rats. Animals were given 0.1% EHEN in their drinking water for the first 2 weeks as an initiator. Subsequently, starting 3 weeks from the commencement, they were fed diet containing these compounds at concentrations of 1000, 500 or 0 ppm until week 26, and then killed for light microscopic examination. The mean numbers of renal tubular cell hyperplasias/cm2 and those of tumors/cm2 in rats given harman and norharman at 1000 ppm after initiation, but not at 500 ppm, were significantly increased as compared to the control values. However, neither compound modified liver carcinogenesis. It is concluded that harman and norharman show enhancing effects on rat kidney carcinogenesis, when ingested at dose levels which cause renal tubular damage.

Animals↗
PubMed1992

The modifying effects of indomethacin or ascorbic acid on cell proliferation induced by different types of bladder tumor promoters in rat urinary bladder and forestomach mucosal epithelium.

The effects of indomethacin (IM) or L-ascorbic acid (AsA) on cell proliferation induced by bladder tumor promoters such as butylated hydroxyanisole (BHA), sodium L-ascorbate (Na-AsA), sodium citrate (Na-Cit), and diphenyl (DP) in rat bladder and forestomach epithelium were investigated. Treatment with IM in combination with BHA or Na-AsA diminished DNA synthesis levels of bladder epithelium as compared to the BHA or Na-AsA alone values. On the other hand, AsA further amplified the increase of bladder epithelial DNA synthesis caused by Na-Cit treatment. Histopathologically, administration of Na-AsA in combination with IM reduced the incidence of simple hyperplasia. In contrast, simultaneous treatment with Na-Cit and AsA caused an increase of the hyperplasia development. No apparent combination effects were observed in the DP-treated groups. In forestomach epithelium, AsA enhanced the BHA-induced increase in DNA synthesis and epithelial hyperplasia, characterized by marked basal cell proliferation. The present results thus suggested that IM may exert inhibitory effects on promotion of bladder carcinogenesis by certain tumor promoter types, and AsA may enhance BHA forestomach carcinogenesis.

Animals↗
PubMed1992

Effects of modifying agents on conformity of enzyme phenotype and proliferative potential in focal preneoplastic and neoplastic liver cell lesions in rats.

Development of preneoplastic lesions in the rat liver under the influence of various modifiers was investigated with particular attention to changes in simultaneous expression of altered enzyme phenotype within the lesions (conformity) and proliferation potential. Degree of conformity of marker enzymes such as glutathione S-transferase placental form (GST-P), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, adenosine triphosphatase and gamma-glutamyltranspeptidase was compared with levels of 5-bromo-2-deoxyuridine labeling. After initiation with diethylnitrosamine, rats were administered the hepatopromoter sodium phenobarbital (PB, 0.05%), the antioxidant ethoxyquin (EQ, 0.5%), or a peroxisome proliferator, clofibrate (CF, 1.0%) or di(2-ethylhexyl)-phthalate (0.3%) and killed at week 16 or 32. The PB promoting regimen was clearly associated with increase in the numbers of high conformity class lesions simultaneously expressing three to five enzymes, and elevated proliferation potential. The inhibitor, EQ, in contrast, brought about a time-dependent decrease in conformity so that only 1 or 2 alterations were most commonly observed at week 32. Lesion populations in the peroxisome proliferator- and especially CF-treated cases were characterized by obvious dissociation between degree of conformity and proliferative status. Such treatment-dependent differences were not always correlated with the size of the lesion. The results thus suggested that the conformity and proliferation potential of preneoplastic lesions are dependent on modification treatment. Overall, GST-P was found to be the most reliable marker, although G6PD was less influenced in the peroxisome proliferator cases.

Adenosine Triphosphatases↗
PubMed1992

Forestomach neoplasm induction in F344/DuCrj rats and B6C3F1 mice exposed to sesamol.

Sesamol was administered at a dietary level of 2% to groups of 30 male and female F344/DuCrj rats and B6C3F1 mice for 104 and 96 weeks, respectively. Squamous cell carcinomas in the forestomach were induced in nine of 29 (31%) effective male rats, three of 30 (10%) female rats, eleven of 29 (38%) male mice and five of 30 (17%) female mice treated with sesamol. Papillomas developed in ten of 29 (34%) male rats and fourteen of 30 (47%) female rats, but not in any of the mice. Hyperplasias developed in almost all rats and mice of both sexes. Significant differences from control values were found for all three lesions in rats and for carcinoma and hyperplasia categories in mice. The incidences of other tumors in the 2% sesamol group were comparable with control values. In conclusion, sesamol induces squamous cell carcinomas in the forestomach of rats and mice, males being more susceptible than females.

Animals↗
PubMed1992

3,2'-Dimethyl-4-aminobiphenyl-induced gallbladder carcinogenesis and effects of ethinyl estradiol in hamsters.

The effects of ethinyl estradiol (EE) on 3,2'-dimethyl-4-aminobiphenyl (DMAB)-induced carcinogenesis were examined in Syrian golden hamsters. DMAB was subcutaneously injected in corn oil at a concentration of 100 mg/kg once a week for 20 weeks and EE was administered in the diet at a dose of 0.75 ppm throughout the experiment. Some animals were killed at week 20 and all surviving ones were killed at week 50. Gallbladder tumors (adenomas and carcinomas) were induced in 6 of 15 hamsters (40%) in the DMAB + EE group and 5 of 14 (36%) in the DMAB alone group in males, and in 6 of 13 (46%) in the DMAB + EE group and 1 of 8 (13%) in the DMAB alone group in females at week 50. A clearer enhancing effect of EE on DMAB gallbladder carcinogenesis was observed for tumor multiplicity (No./animal) for both sexes; from 0.36 to 0.67 in males and from 0.14 to 0.62 in females. Thus, DMAB was demonstrated to be carcinogenic in the gallbladder of hamsters and EE enhanced this DMAB-induced gallbladder tumorigenesis.

Adenocarcinoma↗
PubMed1992

Histomorphological characteristics of cholangiocellular carcinomas in northeast Thailand, where a region infection with the liver fluke, Opisthorchis viverrini is endemic.

Northeast Thailand has a very high incidence rate of intrahepatic biliary tumors which is believed to closely related to infestation with the liver fluke, Opisthorchis viverrini. This study was conducted to ascertain whether there are any phenotypic differences in such tumors between northeast Thailand and Japan, a country free of liver flukes. Forty one intrahepatic cholangiocarcinomas from patients in northeast Thailand were histopathologically compared with 39 lesions collected in Japan. The proportions of each type of adenocarcinoma in the Thailand cases were similar to those of the Japanese cases except that medullary type poorly differentiated tubular adenocarcinoma was only found in the series from Thailand. Whether the presence of medullary lesions only in the cases from the area of endemic fluke infection implies differences in etiology remains in question. The similarity in the majority of histological types, the inflammatory reactions observed in the bile ducts and the earlier development of tumors in association with parasites suggests that tumor promotion resulting from liver fluke infection rather than quantitative or qualitative differences in genetic alterations is responsible for the high frequency of cholangiocellular carcinomas in northeast Thailand.

Adenoma, Bile Duct↗
PubMed1992

Suction effusion fluid from skin and constituent analysis: new candidate for interstitial fluid.

The authors analyzed the constituents of effuse transcutaneous fluid, labeled suction effusion fluid (SEF), and monitored its glucose concentration during glucose loading in rabbits (Japan White, female) under pentobarbital anesthesia. The SEF was sampled by suctioning corneal layer-stripped skin at 400 mmHg absolute pressure. The SEF proved to have nearly the same concentrations as serum for lower-molecular-weight substances such as glucose, creatinine, and urea nitrogens, but not for higher-molecular-weight substances such as serum proteins. The SEF protein concentration was one-fourth that of serum protein. Proteins > 100 kDa molecular mass were barely detectable in the SEF. Monitoring of SEF glucose change every 10 min during intravenous glucose loading was successfully accomplished, and SEF glucose concentration followed blood glucose concentration with a 10-min delay. The SEF was thought to consist of interstitial fluid and/or effuse fluid from small vessels in subcutaneous tissue.

Animals↗
PubMed1992

Collagen deposition and the reversal of coronary reserve in cardiac hypertrophy.

The aim of this study was to clarify how collagen deposition or medial hypertrophy of the vascular wall affects the coronary dilator reserve in pressure-overloaded hearts and whether inhibition of collagen deposition reverses the abnormalities after relief of pressure overload. We used ascending aortic banding and debanding methods and superimposed beta-aminopropionitrile in some of the banded rats (50 mg/kg i.p., twice a day). Ten weeks of banding increased in vivo peak systolic left ventricular pressure and produced medial hypertrophy, an increase in collagen deposition in the myocardial and perivascular tissues, and myocardial hypertrophy in the banded group without beta-aminopropionitrile treatment. Superimposition of beta-aminopropionitrile treatment on banding inhibited the increase in collagen deposition. In the groups debanded after the 10-week banding period, both with and without beta-amino-propionitrile treatment, medial and myocardial hypertrophy regressed 4 weeks after debanding. We estimated coronary dilator reserve in Langendorff preparations perfused with modified Tyrode's solution containing oxygenated bovine red blood cells and serum albumin. The ratio of reactive peak flow after brief ischemia-to-resting flow decreased in both of the banded groups. After debanding, the ratio remained lower in the banded group without beta-aminopropionitrile treatment than in the control group. However, debanding in the group with beta-aminopropionitrile treatment increased the ratio to a level similar to that of the control group. Thus, in pressure-overloaded cardiac hypertrophy with coronary hypertension, coronary reserve seems to be determined by medial hypertrophy independently of collagen deposition, but collagen deposition plays an important role in the reversal of vasodilator reserve after relief of the overload.

Aminopropionitrile↗
PubMed1992

Dose-dependent renal tubular toxicity of harman and norharman in male F344 rats.

The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 week to termination, no mortalities occurred. Marked elevation of water consumption was evident in rats given harman or norharman at 1,000 ppm, but not at 500 ppm, together with large increases in urine of low specific gravity. Urinary lysosomal enzymes (N-acetyl-beta-D-glucosaminidase, NAG, and lactate dehydrogenase, LDH) and sugar levels were increased, and the brush border enzymes (gamma-glutamyl transpeptidase, GGT, and alkaline phosphatase, ALP) decreased. Furthermore, serum biochemistry revealed clear elevation of parameters indicating renal toxicity in these rats. Histopathologically, rats fed 1,000 ppm harman or norharman, but not 500 ppm, demonstrated focal toxic renal degenerative/necrotic and regenerative lesions in proximal, distal, and collecting tubules. These changes were associated with a clearly increased labeling index (LI) of the nuclei of renal tubular epithelial cells on immunohistochemical staining for 5-bromo-2'-deoxyuridine (BrdU). Chemical specific crystal formation within tubular lumina was evident in rats fed 1,000 ppm, but not 500 ppm, this being considered the cause of the renal tubular lesions. It was concluded that harman and norharman exert renal toxicity at the dietary level of 1,000 ppm, but not 500 ppm, in male F344 rats.

Acetylglucosamine↗
PubMed1992

Aging effects on myocardial hypertrophic response and coronary circulation in pressure-overload.

We examined the effect of age on capacity for myocardial hypertrophy, pressure-generating ability and coronary circulation after imposition of pressure-overload. Marked right ventricular and cellular hypertrophy was observed 1 week after pulmonary artery constriction in the developmental phase of rats (2 months of age) and after 3 weeks in the young-adult rats (7 months). In old rats (18 months) similar increases in peak right ventricular pressure did not produce significant hypertrophy even after 3 weeks. The right ventricular hypertrophy at the organ and cell levels in response to pressure-overload decreased with age. In vivo pressure-generating ability, which was determined by maximum isovolumic pressure during pulmonary artery occlusion, correlated with the degree of myocardial hypertrophy in each age group. During the ascending aortic constriction experiment the age-associated diminution in hypertrophic response was also observed in the left ventricle. Coronary dilator capacity, which was determined after brief ischemia in an isolated, blood-perfused, beating but nonworking heart model, was decreased in the presence of myocardial hypertrophy in young-adult rats (7 months) and in the absence of significant myocardial hypertrophy in old rats (18 months). The age-associated diminution in capacity for myocardial hypertrophy, pressure-generating ability and maladaptation in the coronary circulation may explain the higher incidence of heart failure or increased vulnerability of the myocardium to ischemic episodes during hemodynamic stress in aged patients.

Aging↗
PubMed1992

[Assessment of coronary artery bypass grafts by X-ray computed tomography with and without contrast enhancement].

To assess the patency of coronary artery bypass grafts, we tested the capability of X-ray computed tomography (CT) with and without contrast enhancement. This procedure was used on 63 grafts (30 in the LAD; 20 in the LCX; 13 in the RCA) in 32 patients with a mean age of 56 +/- 8 years, all of whom were referred to our department for postoperative management or evaluation. The CT scanner used was Toshiba TCT-60A with a scan time of 3 sec, 5 mm thick slices, and 512 x 512 pixels. CT scans without contrast enhancement were obtained from the level of the aortic arch to the left ventricle. Eight sec after 30 ml of contrast media was injected at a rate of 3 ml/sec into an antecubital vein, 5 scans were made at the same level of the pulmonary artery truncus. After positioning the regions of interests on the ascending aorta and grafts, we obtained time-density curves (TDCs) and compared the data with those recorded from an intraoperative electromagnetic flow meter (EMF). Fifty grafts were angiographically patent. The appearance time, build-up time, peak time, disappearance time and peak densities obtained from TDCs of grafts did not correlate with the flow volumes measured by EMF. Patent grafts were easily identified visually, without contrast enhancement (sensitivity; 88%, specificity; 100%, accuracy; 91%). Occluded grafts were not imaged on CT, either with or without contrast enhancement. We concluded that the TDCs of grafts obtained by CT are of no value for predicting the graft flow, and that plain CT without contrast enhancement is sufficiently useful for assessing the patency of such grafts.

Aged↗
PubMed1992

Latent prostatic carcinomas found at autopsy in men over 90 years old.

Step-sections of 29 whole prostate glands obtained at autopsy from elderly men aged 90 years or over have been investigated. Latent prostatic carcinomas were found in 17 cases (58.6%), all in the peripheral region. The majority of these latent prostatic carcinomas in very old individuals were considered to correspond to stage A1 tumors since, in 75% of cases, the diameter was less than 1 cm. Benign nodular hyperplasia and atypical hyperplasia were also observed in 26 (89.7%) and 14 cases (48.3%), respectively. There was a clear correlation between the appearance of atypical hyperplasia and the presence of latent prostatic carcinoma.

Adenocarcinoma↗