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Biomedical subjects

N Yoshimi

Publications and source records attributed to N Yoshimi.

At least 19 recordsLinked to original sources
PubMed2001

The inhibitory effects of mangiferin, a naturally occurring glucosylxanthone, in bowel carcinogenesis of male F344 rats.

Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-beta-D-glucoside, is one of xanthone derivatives and C-glucosylxanthones, is widely distributed in higher plants and is one of constituents of folk medicines. Recent studies showed that mangiferin has a potential as an anti-oxidant and an anti-viral agent. In this study, we examined the effects of mangiferin in rat colon carcinogenesis induced by chemical carcinogen, azoxymethane (AOM). We performed two experiments: a short-term assay to investigate the effects of mangiferin on the development of preneoplastic lesions by AOM, aberrant crypt foci (ACF), and the following long-term assay for the influence of mangiferin on tumorigenesis induced by AOM. In the short-term assay, 0.1% mangiferin in a diet significantly inhibited the ACF development in rats treated with AOM compared to rats treated with AOM alone (64.6+/-22.0 vs. 108.3+/-43.0). In the long-term assay, the group treated with 0.1% mangiferin in initiation phase of the experimental protocol had significantly lower incidence and multiplicity of intestinal neoplasms induced by AOM (47.3 and 41.8% reductions of the group treated with AOM alone for incidence and multiplicity, respectively). In addition, the cell proliferation in colonic mucosa was reduced in rats treated with mangiferin (65-85% reductions of the group treated with AOM alone). These results suggest that mangiferin has potential as a naturally-occurring chemopreventive agent.

Animals↗
PubMed2000

Frequent beta-catenin gene mutations and accumulations of the protein in the putative preneoplastic lesions lacking macroscopic aberrant crypt foci appearance, in rat colon carcinogenesis.

Activating mutations in the beta-catenin gene is thought to be responsible for the excessive beta-catenin signaling involved in the majority of carcinogen-induced colonic carcinomas. To determine whether beta-catenin signaling is involved in the initial stage of colon carcinogenesis, mutational analysis of the gene and immunohistochemistry for beta-catenin protein were performed in the early appearing lesions, including aberrant crypt foci (ACF), of colonic mucosa in rats given azoxymethane. Male F344 rats received s.c. injections of azoxymethane at a dose of 15 mg/kg body weight, once weekly for 3 weeks, and they were sacrificed 10 weeks after the carcinogen treatment. The colonic mucosa was examined in en face preparations and in serial sections after the observation in whole mount preparations. Microscopical observations in the cross sections have shown two populations of histologically altered crypts. The first type had a macroscopic feature resembling ACF [histologically altered crypts with ACF appearance (HACAs)]. The second type of altered crypts did not have the ACF-like appearance and could not be clearly distinguished from adjacent normal crypts in whole mount preparations [histologically altered crypts with macroscopically normal-like appearance (HACNs)]. The beta-catenin gene mutations were recognized in 10 of 15 HACNs (67%) and 3 of 15 HACAs (20%). Frequent immunoreactivity of beta-catenin protein was seen in the cytoplasm of HACNs (13 of 15 cases), whereas apparent accumulation was not confirmed in any HACAs analyzed. These results suggest that (a) there are two types of putative preneoplastic lesions in cancer-predisposed colonic mucosa, and beta-catenin signaling may contribute to the initial stage of colon carcinogenesis; and (b) HACNs are more likely to be direct precursors of colon tumors than HACAs in the rat colon carcinogenesis.

Amino Acid Substitution↗
PubMed2000

Increase of fragmented DNA transport in apical dendrites of gerbil CA1 pyramidal neurons following transient forebrain ischemia by mild hypothermia.

Mild hypothermia (38 degrees C) accelerated transport of fragmented DNA in apical dendrites of the gerbil CA1 pyramidal neurons and increased dendrite-terminal fragmented DNA pooling in the apoptotic process following transient forebrain ischemia. The specific DNA fragmentation after the ischemic insult in gerbil hippocampus was examined by in situ nick-end-labeling method, and fluorescence DNA detection technique by DAPI was also performed. There is a precise temperature dependence for the migration of fragmented DNA from nuclei into apical dendrites of CA1 pyramidal cells during apoptosis following transient forebrain ischemia. Increase of fragmented DNA pooling is highly temperature sensitive, occurring at 38 degrees C, while at 39 degrees C there is a marked decrease in DNA pooling.

Animals↗
PubMed2000

Effects of Fas-mediated liver cell apoptosis on diethylnitrosamine-induced hepatocarcinogenesis in mice.

The present study was designed to investigate the effect of Fas-mediated liver cell apoptosis, induced by a hamster monoclonal antibody against mouse Fas antigen, on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. DEN (10 microg g(-1), intraperitoneally (i.p.)) was given to 15-day-old male C3H/HeJ mice. Three weeks after DEN treatment, Fas-mediated liver cell apoptosis induced by anti-Fas antibody resulted in a biphasic effect on induction of liver cell tumours, depending on dosage and time of antibody administration. Single or multiple treatment with high dose anti-Fas antibody (5 microg animal(-1)), induced gross liver cell damage and decreased the incidence of liver cell tumours in DEN-treated mice. In contrast, five treatments with low dose anti-Fas antibody (2 microg animal(-1)), induced dispersed localized liver cell damage and promoted the number of large-sized liver cell adenomas and hepatocellular carcinomas. These findings suggest that high dose anti-Fas antibody has a marked effect on the clearance of DEN-initiated liver cells, whereas repeated administration of low dose anti-Fas antibody promotes hepatocarcinogenesis. It is concluded that Fas-mediated liver cell apoptosis has a biphasic effect on hepatocarcinogenesis.

Adenoma↗
PubMed2000

Differential expression of beta-catenin in human glioblastoma multiforme and normal brain tissue.

Angiogenesis is considered to play an important role in the development of malignant brain tumors, especially glioblastoma multiforme (GBM). Abnormal vascular construction with a glomeruloid appearance is characteristic of GBM. beta-catenin is known as one of the adhesive molecules associated not only with cell adhesion and cell polarity, but also with carcinogenesis. We postulated the relevance of beta-catenin to vigorous endothelial proliferation in human GBM because the vascular cells (VCs) are apt to lose their cell polarity. The object of this study is to compare the immunohistochemical localization of beta-catenin in VCs between GBMs and normal brain tissues. Immunohistochemical analysis of beta-catenin for VCs in 32 GBMs and 10 normal brain tissues was performed. beta-catenin was found concentrated in the areas of vascular cell-cell junction and internal surface of the vascular lumen in all normal brains. In contrast, beta-catenin, in proliferating VCs in GBMs, was stained homogeneously and intensely in the cytoplasms of 26 cases (81.3%), in which nuclear staining of beta-catenin was also recognized in four cases (12.5%). In conclusion, the intracellular localization of beta-catenin in VCs of GBMs was found to be different from that of normal brain tissues. The changes of expression of beta-catenin may be associated with the angiogenesis or transformation of the VCs in human GBM.

Brain↗
PubMed2000

Centrosomal kinases, HsAIRK1 and HsAIRK3, are overexpressed in primary colorectal cancers.

Members of the recently identified family of Homo sapiens Aurora / Ipl1-related kinases (HsAIRKs), homologous to chromosome segregation kinases, fly Aurora and yeast Ipl1, are highly expressed during M phase, and have been suggested to regulate centrosome function, chromosome segregation, and cytokinesis. In the present study, immunohistochemical analyses were performed of HsAIRK1 and HsAIRK3 expression in 78 primary colorectal cancers and 36 colorectal adenomas as well as 15 normal colorectal specimens. In normal colon mucosa, some crypt cells showed weak positive staining in 10 and 12 out of 15 cases for HsAIRK1 and HsAIRK3, respectively, the remaining cases being negative. Elevated expression of HsAIRK1 was observed in 53 (67.9%) of the colorectal cancers, and of HsAIRK3 in 40 (51.3%). Furthermore, colorectal adenomas showed high expression of HsAIRK1 and HsAIRK3 in 11 (30.6%) and 7 (19.4%) cases, respectively, thus being intermediate between colorectal cancers and normal colorectal mucosa. Interestingly, HsAIRK1 overexpression was significantly associated with pT (primary tumor invasion) and p53 accumulation in colorectal cancers. There was no significant correlation between proliferating cell nuclear antigen-labeling index (PCNA-LI) and the levels of these proteins. The results suggest that overexpression of HsAIRK1 and HsAIRK3 might be involved in tumorigenesis and / or progression of colorectal cancers.

Adenoma↗
PubMed2000

Technetium tin colloid test detecting symptomless dysphagia and ACE inhibitor prevented occurrence of aspiration pneumonia.

Symptomless dysphagia and swallowing disorders play a very important role in the pathogenesis of aspiration pneumonia. A videofluoroscopic examination and a simple two-step swallowing provocation test (STS-SPT) could be useful for detection of swallowing disorders in elderly patients with stroke, however, there is no report on such a test for detection of symptomless dysphagia. We administered 1 ml Technetium Tin Colloid (99mTC) to the patient during sleep via a nasal catheter placed in the mouth. At 09:00 h the next day, symptomless dysphagia was checked for by imaging. Improvement of the symptomless dysphagia was observed, and thus we could prevent the occurrence of aspiration pneumonia. The 99mTC test was particularly useful in detecting symptomless dysphagia in elderly patients with stroke.

Aged↗
PubMed2000

Inhibition of azoxymethane-induced rat colon carcinogenesis by potassium hydrogen D-glucarate.

While calcium D-glucarate was shown to inhibit chemical carcinogenesis in various animal models, the effect of potassium hydrogen D-glucarate has not been extensively investigated. In the present study, potassium hydrogen D-glucarate markedly inhibited azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. Potassium hydrogen D-glucarate (PHG) or potassium hydrogen carbonate (PHC) were administered to rats in a diet (140 mmol/kg). Continual post-initiation treatment with potassium hydrogen D-glucarate reduced both tumor incidence and multiplicity at sacrifice by ca. 60%, while PHC had no effect. amelioration of overexpression of the betaG gene in rat colon carcinomas was observed using RT-PCR and Northern blot analysis. We hypothesize that previously demonstrated conversion of PHG to D-glucaro-1,4-lactone, a potent inhibitor of beta-glucuronidase (betaG), may be responsible for this effect. The mechanism of PHG inhibition of colon carcinogenesis may also involve suppression of cell proliferation and possibly alterations in cholesterol synthesis or cholesterol metabolism to bile acids. In conclusion, PHG possesses excellent potential as a natural, apparently non-toxic inhibitor to prevent colon cancer.

Animals↗
PubMed2000

Immunohistochemical analysis of beta-catenin in N-ethyl-N-nitrosourea-induced rat gliomas: implications in regulation of angiogenesis.

Angiogenesis plays an important role in the development of malignant brain tumors. We postulated the involvement of beta-catenin, which is associated with not only cell adhesion but also tumorigenesis in some neoplasms, in angiogenesis in brain tumors. We performed an immunohistochemical analysis of beta-catenin for vascular cells (VC) in 45 N-ethyl-N-nitrosourea (ENU)-induced rat gliomas and rat normal brain tissues. As a result, beta-catenin was found concentrated in the vascular cell-cell junction and internal surface of the vascular lumen in all normal brains. In contrast, proliferating VC in tumors were stained homogeneously in the cytoplasms of 35 cases (77.8%), among which nuclear staining was also recognized in 12 cases (26.7%). The proliferative potential of VC, which was evaluated by nucleolar organizer region-associated argyrophilic protein (AgNOR), was higher in all types of tumors than in normal brains, and was basically in parallel with the degree of malignancy of the tumors. Thus, it was suggested that the tumor vessels proliferate under a relationship with the proliferative potential of the tumors, and the intracellular localization of beta-catenin is changed under the influence of proliferative potentials of VC. beta-catenin in normal VC is considered to maintain the polarity of the vascular structure, and thus aberrant localization of beta-catenin may result in the loss of structural polarity of the tumor vessels.

Animals↗
PubMed2000

Immunohistochemical expression of glutathione transferase-pi in untreated primary non-small-cell lung cancer.

Patients with unresectable non-small-cell lung cancer (NSCLC) usually have undergone chemotherapy; however, such problems as resistance to chemotherapeutic agents occur during the treatments. Recent studies have indicated that glutathione S-transferase-pi (GST-pi) may play an important role in the resistance of cancer cells to alkylating agents, including cisplatin compounds. We examined a possible relationship between immunohistochemical expression of GST-pi and the response to cisplatin plus etoposide chemotherapy in patients with untreated and unresectable primary NSCLC. Of the 89 patients, 50 (56.2%) were GST-pi-positive and 39 (43.8%) were GST-pi-negative. For the patients with negative GST-pi expression, the response rate was 66.7% (26 of 39 patients). In the patients with positive GST-pi expression, the response rate was 26% (13 of 50 patients). This difference was statistically significant (P = .0019). The results suggest that GST-pi expression in NSCLC tissues is related to response to cisplatin plus etoposide chemotherapy and may be useful as a predictor of chemotherapy response.

Adenocarcinoma↗
PubMed1999

Failure of preventive effects of 2-deoxy-D-glucose on ischemia-induced gerbil hippocampal neuronal damage by induced hyperthermia.

Post-ischemic administration of 2-deoxy-D-glucose (2-DG), a glucose antimetabolite, markedly reduces the occurrence of ischemia-induced delayed neuronal death (DND) in the gerbil hippocampus. This means that the reduction of energy dependent metabolism after ischemia prevents ischemia-induced damages of hippocampal neurons. In the present study, we demonstrated hyperthermia during ischemia fails to preserve neurons in hippocampal CA1 of 2-DG treated gerbil following transient forebrain ischemia.

Animals↗
PubMed1999

Control of cell proliferation in cancer prevention.

Control of cell proliferation is important for cancer prevention since cell proliferation has essential roles in carcinogenesis including the process of initiation and promotion. In rodent models for carcinogenesis, especially those for the carcinogenesis in digestive organs such as colon, liver or oral cavity, chemopreventive agents suppress carcinogen-induced hyperproliferation of cells in the target organs during the initiation as well as the postinitiation phases. Therefore, effective agents usually suppress cell proliferation and inhibit the occurrence of malignant lesions. Availability of new biomarkers for cell proliferation, apoptosis or telomerase activity could be promising. By combining the use of intermediate biomarkers including premalignant lesions such as aberrant crypt foci in the colon or enzyme-altered foci in the liver and cell proliferation, short-term screening of effective chemopreventive agents will be possible.

Animals↗
PubMed1999

Inhibition of tumor necrosis factor-alpha induced neutrophil apoptosis by cyclic AMP: involvement of caspase cascade.

Treatment of neutrophils with tumor necrosis factor-alpha (TNF-alpha) in the presence of cycloheximide induced apoptosis within 3 h, as evaluated by the occurrence of morphological nuclear changes characteristic of apoptosis. Pretreatment of neutrophils with dibutyryl cyclic AMP (dbcAMP) suppressed the TNF-alpha/cycloheximide-induced apoptosis in neutrophils in a concentration-dependent manner, while dbcAMP by itself did not induce any morphological changes. Forskolin, or a phosphodiesterase inhibitor, also produced a concentration-dependent inhibition on apoptosis. This inhibition by dbcAMP was completely reversed by pretreatment with the protein kinase A inhibitor, N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline sulphonamide (H-89). DbcAMP also inhibited the TNF-alpha/cycloheximide-induced activation of caspase-3, but it had no effect on the activation of caspase-8 in human neutrophils. Furthermore, dbcAMP did not directly inhibit activated caspase-3 activity. Inhibitor of protein kinase C, phosphatidylcholine-specific phospholipase C, tyrosine kinase, nitric oxide synthase, or granulocyte colony-stimulating factor or granulocyte monocyte colony-stimulating factor did not affect apoptosis. These results indicate that the elevation of levels of endogenous intracellular cyclic AMP and subsequent activation of protein kinase A play a crucial role in the prevention of apoptosis triggered by TNF-alpha/cycloheximide in human neutrophils, and that the possible target of cyclic AMP is a product in the metabolic pathway between caspase-8 and caspase-3.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1999

Frequent mutations of the rat beta-catenin gene in colon cancers induced by methylazoxymethanol acetate plus 1-hydroxyanthraquinone.

Recent evidence suggests that the beta-catenin gene (CTNNB1) acts as an oncogene, and some human colon tumors with an intact APC gene have activating mutations in CTNNB1. In this study, mutations in the region corresponding to N-terminal phosphorylation sites (codons 1-51) of the rat Ctnnb1 gene were investigated in 20 colon tumors associated with ulcerative colitis and induced with methylazoxymethanol acetate and 1-hydroxyanthraquinone. Ninety percent (18 of 20) of the tumors induced in male F344 rats harbored mutations, which were detected in three of four adenomas (75%) and 15 of 16 adenocarcinomas (94%). Of 18 total missense mutations, 13 (72%) were G-->A transitions at position 101, three were G-->A transitions at position 94, and two were C-->T transitions at position 122, resulting in the amino acid substitutions Gly34-->Glu, Asp32-->Asn, and Thr41-->Ile, respectively. Although there were no mutations in the Apc gene, as we previously reported in the same tumor samples, the results obtained in this study strongly implicate the Apc-beta-catenin-T-cell factor (Tcf) signaling pathway in methylazoxymethanol acetate, 1-hydroxyanthraquinone-induced colon carcinogenesis.

Adenocarcinoma↗
PubMed1999

Prevention of ischemia-induced hippocampal neuronal damage by 2-deoxy-D-glucose in gerbils.

It has been reported that delayed neuronal death (DND) in the hippocampus following transient forebrain ischemia is associated with internucleosomal DNA fragmentation, indicating apoptosis. This suggests that the process of DND is energy dependent. Transient severe forebrain ischemia was induced in Mongolian gerbils by bilateral occlusion of the common carotid arteries. Post-ischemic administration of 2-deoxy-D-glucose (2-DG), a glucose antimetabolite, markedly reduced the occurrence of ischemia-induced DNA fragmentation and DND in the hippocampus. These results suggest that the reduction of energy dependent metabolism after ischemia may be an attractive therapeutic strategy for preserving hippocampal neurons vulnerable to ischemia.

Animals↗