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Biomedical subjects

N Ito

Publications and source records attributed to N Ito.

At least 307 records · Page 17Linked to original sources
PubMed1994

Responses to hemodynamic stress in the aged heart.

In aged individuals the incidence of heart failure is higher than in younger subjects. Ischemic events are also common in the aged heart because of changes in the coronary vasculature and myocytes caused by aging. Adaptational responses to increased hemodynamic overload and to ischemia in the aged heart are discussed at the molecular, cellular and organ levels. One characteristic of the aged heart is a limited capacity for adaptation with hypertrophy to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun by hemodynamic stress. This diminution results from the aging of the heart per se and may be modulated by extracardiac factors. An age-related diminution was also observed in the mRNA induction of heat shock proteins by transient ischemia. However, this diminished induction of immediate early genes in the aged heart was not observed after more severe stress. With regard to the coronary vasculature, the age at which pressure-overload begins seems to be one of the important factors which determine the vascularity of hypertrophied hearts. Late-onset pressure-overload decreased dilator reserve in spite of the absence of myocardial hypertrophy. Thus, the responses to stress in the aged heart are quite different from those in the young heart. The limited capacity for adaptation to hemodynamic overload and poor protective mechanisms against stress may be causes of the higher incidence of heart failure in the aged.

Aged↗
PubMed1994

Medium-term rat liver bioassay for rapid detection of carcinogens and modifiers of hepatocarcinogenesis.

For rapid detection of carcinogenic agents, a medium-term liver bioassay has been established in our laboratory using preneoplastic glutathione S-transferase placental form (GST-P) positive foci in the rat liver as endpoint marker lesions. A total of 237 compounds have so far been tested in this system and the results compared with reported Salmonella/microsome and long-term carcinogenicity test findings. The positive rate was found to be extremely high, 97% (28 of 29 compounds) for genotoxic hepatocarcinogens; and satisfactory, 86% (23 of 27 chemicals) for nongenotoxic ones. The positive rate for carcinogens targeting organs other than the liver, however, is relatively low (24%). Malathion and vinclozolin proved positive, although both have been reported to be noncarcinogenic in rats and mice. Those chemicals which exerted positive results in this system might be hepatopromoting agents even if hepatocarcinogenicity has not been established. Five of the six false-negative hepatocarcinogens could be categorized as peroxisome proliferators. In addition, a number of inhibitory agents for GST-P-positive foci development have been detected and many are categorized as antioxidants. The validity of this system as a tool for rapid detection of carcinogenic and chemopreventive agents is discussed.

Animals↗
PubMed1994

Alteration in growth regulation of hepatocytes in primary culture obtained from cirrhotic rat: poor response to transforming growth factor-beta 1 and interferons.

Cell growth appears to be controlled by positive and negative cell growth regulation. Little is known about the growth regulation of hepatocytes in the cirrhotic liver. Clarifying the responses of hepatocytes obtained from cirrhotic liver to various growth factors and growth inhibitory factors might aid understanding of alterations in growth regulation of the hepatocytes in the cirrhotic liver. We investigated the effects of hepatocyte growth factor, epidermal growth factor, heparin-binding epidermal growth factor-like growth factor, transforming growth factor-beta 1, interferon-alpha and interferon-gamma on the DNA synthesis of hepatocytes from cirrhotic and normal rats in primary culture. Cirrhosis was induced in male Sprague-Dawley rats by means of oral administration of 0.05% thioacetamide in drinking water for 4 mo. Hepatocytes were isolated by means of an in situ perfusion method, and DNA synthesis was assessed from the amount of DNA-incorporated [3H]thymidine. Stimulation of the DNA synthesis of hepatocytes by hepatocyte growth factor, epidermal growth factor and heparin-binding epidermal growth factor-like growth factor was not different between normal and cirrhotic rat liver. Transforming growth factor-beta 1 inhibited the DNA synthesis of hepatocytes in both. However, the concentration of transforming growth factor-beta 1 giving a 50% inhibition of DNA synthesis was about two times higher in cirrhotic hepatocytes (0.11 ng/ml) than in normal hepatocytes (0.06 ng/ml). In cirrhotic hepatocytes, the expression of transforming growth factor-beta type II receptor gene was about 50% of that in normal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Association of antibodies to Opisthorchis viverrini with hepatobiliary disease in northeastern Thailand.

The association between Opisthorchis viverrini infection and hepatobiliary disease was studied in northeastern Thailand. Positive rates of O. viverrini infection and antibody titers to O. viverrini adult worm extracts, which were determined by enzyme-linked immunosorbent assay (ELISA), were compared among four groups: Thai patients with cholangiocarcinomas (CHCA), those with calculus cholecystitis (CCLT), endemic area victims of traffic accidents, and Japanese individuals used as negative controls. While no difference was observed between cases with CCLT and the accident victims, the CHCA group showed a significantly higher positivity rate for fluke infection and higher antibody titers than the other groups. Comparison of the positivity rates and ELISA titers among intrahepatic and extrahepatic CHCA subgroups showed that only females with intrahepatic tumors had a low positive rate and significantly lower titers, with no other significant variation being evident. From these observations, a strong association between high intensity of past and/or present O. viverrini infection and the genesis of CHCAs was apparent in the majority of cases. However, in addition to the fluke infection, other unknown exogenous or endogenous factor(s) were suggested in the female cases.

Adolescent↗
PubMed1994

[A double blind controlled study on S6472 capsules and granules in complicated urinary tract infection].

The efficacy, safety and usefulness of S6472 capsules (cefaclor, long-acting preparation) were investigated in non-catheterized patients with complicated cystitis using the double blind method with S6472 granules as a control. Each of the patients was orally administrated with 375 mg of the drug twice a day for 7 days, and clinical effectiveness was evaluated according to the Criteria of Drug Efficacy of UTI (the Third Edition). The following results were obtained. 1. There was no significant bias between the capsule-administrated group (A) and the granule-administrated group (B) in background factors. 2. The overall clinical efficacy rates were 78.7% in Group A and 80.5% in Group B, which showed no significant difference. No significant difference was observed also between groups IV and VI in the efficacy for any of the UTI groups. 3. Eradication rates in bacteriological response were 85.9% and 86.0% in Group A and B, respectively. 4. Clinical efficacy rates evaluated according to doctors in charge of patients were 78.7% and 74.7% in Group A and B, respectively, showing no significant difference between the two groups. 5. The incidences of adverse reactions were 3.0% in Group A (3 out of 101 cases) and 7.1% in Group B (7 out of 98), thus no significant difference was found between the two groups. Abnormal test values in laboratory examinations included 5 cases (in 4 among 75 patients) in Group A, but were not detected in any of the 76 patients in Group B. No statistically significant difference were observed between the two groups, however. 6. No significant difference between the two groups was observed in the usefulness evaluation including efficacy and safety profiles on an analog scale by the doctors in charge of patients. These results indicate that S6472 capsules have the same efficacy, safety and usefulness as S6472 granules, suggesting that both drugs are equally excellent for non-catheterized patients with complicated cystitis.

Adolescent↗
PubMed1994

[Ultrasonography in the diagnosis of malignant lymphoma of the thyroid].

Malignant lymphoma of the thyroid was rare condition and it was difficult to make a diagnosis of malignant lymphoma preoperatively. Both ultrasonographic appearance and diagnostic significance of ultrasonography in malignant lymphoma of the thyroid were investigated in this study. Ultrasonography of 10 patients with malignant lymphoma of the thyroid was analyzed. Only 3 cases of 10 were diagnosed as malignant lymphoma by ultrasonography. Five cases were misdiagnosed as thyroid carcinoma, 1 as adenomatous goiter accompanied by cystic degeneration and 1 as chronic thyroiditis. Nine cases were nodular type i.e. limited extremely hypoechoic mass as contrasted with surrounding thyroid tissue, occupying asymmetrically in the thyroid gland. One case was diffuse type i.e. diffused hypoechoic area without surrounding residual thyroid tissue. The tumor size of the 2 cases in which no accumulation was observed in the 67Ga scintigram was 2 cm or less. By ultrasonography of these 2 cases, one case was diagnosed as malignant lymphoma and the other as thyroid carcinoma. Ultrasonography can be regarded to be very significant method as a screening test to make a diagnosis of malignant tumor for nodular type, especially small sized malignant lymphoma of the thyroid.

Aged↗
PubMed1993

Enhancement by non-mutagenic pesticides of GST-P positive hepatic foci development initiated with diethylnitrosamine in the rat.

The potential hepatocarcinogenicity of seven pesticides was examined using a rapid bioassay based on the induction of glutathione S-transferase placental form positive foci in the rat liver. Rats were initially injected with diethylnitrosamine and two weeks later were fed on diet supplemented with one of the pesticides for 6 weeks and then killed; all rats were subjected to a partial hepatectomy at week 3. Positive results were seen with chlorobenzilate (2000 ppm), vinclozolin (2000 ppm), malathion (4000 ppm), tecnazene (2000 ppm) and isoproturon (2000 ppm). S,S,S-tributylphosphorotrithioate (DEF, 200 ppm) and dicloran (2000 ppm) were negative in both number and area analyses. Although chlorobenzilate is carcinogenic in mice, malathion and vinclozolin have been reported as non-carcinogens in both rats and mice. Since the present system is based on the two-stage carcinogenesis hypothesis, it is possible that the chemicals showing positive results in this system possess at least tumor-promoting activity in the rat liver. This is very significant, as most carcinogens show tumor-promoting activity in their target organs.

Animals↗
PubMed1993

Mechanism of lipopolysaccharide-triggered junB activation in a mouse macrophage-like cell line (J774).

The effect of lipopolysaccharide (LPS) on the activation of junB in a mouse macrophage cell line (J774) was investigated. J774 cells responded to either phorbol 12-myristate 13-acetate (PMA) or LPS by the transient increase in the expression levels of c-jun and junB mRNA, but not of junD mRNA. The prior depletion of protein kinase C from J774 cells blocked the action of PMA, but not of LPS, to activate junB. Pretreatment of cells with H-89 or H-7, but not with HA1004, W-7, ML-7, or tyrphostin 47, inhibited LPS-triggered junB activation. Treatment with forskolin also activated junB of J774 cells through an H-89- or H-7-sensitive pathway. Since cAMP-dependent protein kinase activity of J774 cells was inhibited by H-89, but not by H-7, LPS appears to activate junB through a cascade involving two steps, the one sensitive to H-89 and the other to H-7. Western blot analysis showed that LPS-triggered junB activation is accompanied by the increased expression of JunB proteins in the cell lysate as well as in the nuclear extract. JunB in nuclear fraction appears to specifically bind to 12-O-tetradecanoylphorbol-13-acetate-response element (TRE), since preincubation of nuclear extracts with anti-JunB serum reduced the amount of TRE-binding proteins and since the amount of JunB, but not of c-Jun or JunD, immunoprecipitated from TRE-cross-linked nuclear proteins increased in response to LPS. Thus, JunB may play an important role in LPS-triggered gene activation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Carcinogenic potential of some pesticides in a medium-term multi-organ bioassay in rats.

The carcinogenic potential of 5 pesticides was analyzed using a medium-term multi-organ bioassay for carcinogenicity. Male F344 rats were initially treated with 3 known carcinogens (diethylnitrosamine, N-methyl-N-nitrosourea and N-bis(2-hydroxypropyl)nitrosamine) during a period of 4 weeks to induce neoplastic changes in a variety of organs, and then given one of 5 pesticides in the diet for a further 16 weeks. Neoplastic and pre-neoplastic lesions were found in the thyroid, kidney and urinary bladder with propineb, in the forestomach, kidney and thyroid with captan and folpet. The number of glutathione S-transferase placental-form-positive liver-cell foci was significantly increased in the captan- and phosmet-treated groups. Based on these findings, captan and propineb can be considered as carcinogens and carcinogenicity is suspected for folpet and phosmet. These results are in concordance with reported long-term carcinogenicity for captan, folpet and propineb. Daminozide was considered not to be carcinogenic. Thus, the present assay of 20 weeks' duration is useful for the prediction of potential carcinogens.

Animals↗
PubMed1993

Aromatase activity in human hepatocellular carcinoma. Relationship with the degree of histologic differentiation.

Human hepatocellular carcinomas (HCC) were examined aromatase activity, an enzyme that converts androgen into estrogen. Such activity was detected in all 13 specimens of HCC (mean activity, 120 fmol/30 min/mg microsomal protein). The activity tended to be lower in the HCC tissue than in the surrounding liver tissue (mean activity, 230 fmol/30 min/mg microsomal protein), although it was higher in the HCC tissue from three of eight patients with Edmondson's Grade 2 disease. This relationship was not found in the five with Grade 3 disease. On the whole, aromatase activity was significantly higher in specimens from patients with Edmondson's Grade 2 tumors than in the less differentiated Grade 3 type (P < 0.05). These observations suggested that aromatase activity was present in human HCC and was related to the degree of histologic differentiation.

Aged↗
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

Rare frequency of activation of the Ki-ras gene in rat colon tumors induced by heterocyclic amines: possible alternative mechanisms of human colon carcinogenesis.

Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymerase chain reaction--direct sequencing in seven colon tumors in F344 rats induced by 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1), 11 induced by 2-amino-3-methylimidazo[4,5-f]quinoline, and nine induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A Ki-ras gene mutation (G-->T at the second position in codon 12) was found in one Glu-P-1-induced colon adenocarcinoma. None of the other 26 tumors had mutations in any of these three ras family genes. These results indicate that in rats, colon carcinogenesis induced by heterocyclic amines may be induced by alterations of other oncogenes or tumor suppressor genes. We think this experimental system using carcinogens to which humans are exposed is a good model for studying alterations of other genes in human colon tumors in which no Ki-ras alterations are observed.

Adenocarcinoma↗
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

Coronary dilator reserve and morphological changes after relief of pressure-overload in rats.

Using a rat model of short- (4 weeks) and long-term (10 weeks) ascending aortic banding and debanding, we examined the relationship between coronary dilator reserve and morphological vascular changes. After 4 or 10-week banding, in vivo systolic left ventricular pressure and ventricular wt/body wt ratio increased to a similar level, compared with controls. The coronary dilator reserve measured in an isolated heart preparation decreased similarly in the two banded groups, compared with controls. The ratios of medial to luminal area and perivascular collagen to luminal area in coronary microvessels increased in the banded groups. At 4 weeks after debanding, cardiac hypertrophy regressed to the control level, and the duration of banding did not alter the extent of the regression. The coronary dilator reserve normalized in the group debanded after 4-week banding, but did not regress in the group debanded after 10-week banding. In both of the debanded groups, the hypertrophied media regressed completely. The increased perivascular collagen regressed almost completely in the group debanded after 4-week banding, but remained greater in the group debanded after 10-week banding than in the controls. From these results, we conclude that (i) the regression of medial hypertrophy does not always improve the decreased coronary dilator reserve, and (ii) the vascular fibrosis may be the major cause of the irreversibility of decreased coronary dilator reserve in long-term cardiac hypertrophy.

Animals↗
PubMed1993

Histochemical analysis of blood group antigens in human sublingual glands and pancreas. An application of high-performance liquid chromatography to estimate the quantity of galactose liberated from tissue sections by alpha-galactosidase digestion.

Using immunostaining with monoclonal antibodies (mAbs) from three different sources as well as anti-B lectin, GSAI-B4 staining and alpha-galactosidase digestion, blood group B antigens were localized and analysed in tissue sections of sublingual glands from blood group B and AB individuals. Quantitative analysis of galactose was simultaneously carried out on the supernatant enzyme solution used for treating tissue sections by high-performance liquid chromatography (HPLC). In addition, galactose liberated from the pancreas tissues of blood group B and AB individuals was also estimated by HPLC analysis in order to compare the content of antigens. mAb-B(H079) and GSAI-B4 reacted uniformly with the mucous cells from blood group B and AB secretors. On the other hand, other mAbs-B(B006 and A582) recognized the antigen in a limited number of cells or was even negative in some cases of blood group AB individuals. Only mAb-B(H079) recognized the B antigens in mucous cells from non-secretors. Digestion with alpha-galactosidase resulted in the consistent appearance of H and Le(b) antigens in the mucous cells of all the secretors examined, although the reduction of staining intensity with anti-B reagents was not so marked. Le(y) antigens also appeared in some cases after the enzyme digestion. In non-secretors, Le(b) and Le(y) antigens, but not H antigens, appeared in some mucous cells following enzyme digestion. HPLC analysis of galactose revealed that alpha-galactosidase can specifically liberate the terminal galactose residues of B antigens, and no marked difference was present in the content of liberated galactose from mucous cells of sublingual glands among the individuals investigated (8.5-11.7 nmoles cm-2). No galactose was detected in samples from the sublingual glands of non-secretors, and only a trace amount of galactose was detected in the samples from pancreas tissues. These results suggest that the observed difference in the reactivity of different reagents with each tissue site can be ascribed to both quantitative and qualitative heterogeneity of B antigens.

Blood Group Antigens↗
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↗