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N Yoshimi

Publications and source records attributed to N Yoshimi.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Neuronal apoptosis studied by a sequential TUNEL technique: a method for tract-tracing.

A novel tract-tracing procedure by using a sequential in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling of DNA fragments (TUNEL) is described. This method identifies fragmented DNA transported into neuronal fibers in tissue sections of gerbil hippocampal CA1 neurons following transient forebrain ischemia. The transported DNA has been confirmed by another method, fluorescence DNA detection technique by DAPI. Many methods have been developed to study the neuroanatomical connections in the central nervous system. Principally, these techniques are based on tract-tracing studies using xenobiotics into the central nervous system. Our tract-tracing method is originated from an intrinsic marker that is produced during the apoptotic process of neurons. Furthermore, the advantage of this method is that only the selected cells undergoing apoptosis are recognized and traced to the end of the related neuronal fiber. Usually, apoptotic cells possess intact intracellular metabolic mechanisms until completion of cell death. Thus, apoptotic neurons retain the axonal transport mechanisms which enables us to detect fragmented DNA moving from nuclei to distal terminals of neuronal fibers. Since TUNEL-positive DNA movement within neuronal fibers occurs only during a limited period, it is essential that a time-course of the TUNEL technique is used to study tract-tracing of apoptotic neurons. Although this method can identify only the apical dendrites of cells that are undergoing apoptosis during the limited period, some projections of the gerbil hippocampal CA1 neurons undergoing apoptosis are clearly demonstrated.

Animals↗
PubMed1999

Dietary prevention of azoxymethane-induced colon carcinogenesis with rice-germ in F344 rats.

The modifying effect of dietary administration of defatted rice-germ and gamma-aminobutyric acid (GABA)-enriched defatted rice-germ on azoxymethane (AOM)-induced colon carcinogenesis was investigated in two experiments with male F344 rats. In the first experiment (the pilot study), the effects of the defatted rice-germ, the GABA-enriched defatted rice-germ and rice-germ on AOM-induced (15 mg/kg body wt once a week for 3 weeks) formation of aberrant crypt foci (ACF) were examined. The latter two preparations (2.5% in the diet) significantly inhibited ACF formation (P < 0.005). In the second experiment, a long-term study of the effects of rice-germ was done. One group was treated with AOM alone, four groups received the carcinogen and were fed the diets containing 2.5% rice-germ or 2.5% GABA-enriched defatted rice-germ for 5 (initiation phase) or 30 weeks (post-initiation phase), two groups were treated with rice-germ or GABA-enriched defatted rice-germ alone and one group was kept on the basal diet. At the termination of the study, dietary exposure to rice-germ during the initiation phase significantly reduced the incidence of colonic adenocarcinoma (71 versus 29%, P < 0.01). GABA-enriched defatted rice-germ or rice-germ during the post-initiation phase also decreased the frequency of colonic adenocarcinoma (71 versus 20%, GABA-enriched defatted rice-germ feeding, P < 0.01; 27%, rice-germ feeding, P < 0.01). These data suggest that constituents of rice-germ are possible dietary preventatives for human colon cancers.

Animals↗
PubMed1999

Chemopreventive effect of N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide (NS-398), a selective cyclooxygenase-2 inhibitor, in rat colon carcinogenesis induced by azoxymethane.

Non-steroidal anti-inflammatory drugs (NSAIDs) such as sulindac and indomethacin inhibit colon carcinogenesis, and selective cyclooxygenase (COX)-2 inhibitors are considered to be potential chemopreventive agents without the side effects of usual NSAIDs. We reported that NS-398, N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide, suppressed the formation of preneoplastic lesions, aberrant crypt foci (ACF), induced by azoxymethane (AOM) in a short-term assay of rat colon carcinogenesis. In this study, we examined the effects of long-term NS-398 administration on rat colon carcinogenesis. After three AOM treatments at weekly intervals, a dose of 10 mg/kg of NS-398 in 5% Arabic gum solution was administered by gavage three times per week in group 2 until the termination of the experiment. Rats in group 1 were fed in a basal diet and given 5% Arabic gum solution alone after AOM treatment. At 40 weeks after the first AOM treatment, all rats were killed and the whole intestines including colon were examined. While the incidences of whole intestinal and colon neoplasms in group 1 were 84.6% and 80.8%, respectively, those in group 2 (given NS-398) were 51.9% and 44.4% respectively (P=0.0177 and P=0.0103 by Fisher's exact test, respectively). The multiplicities in group 2 (0.67+/-0.78 and 0.48+/-0.58) were also decreased significantly compared with those (1.39+/-1.10 and 1.08+/-0.74) in group 1 (P<0.01 by Welch's method and P<0.002 by Student's t test, respectively). In immunohistochemistry for proliferative cell nuclear antigen (PCNA), the PCNA-stained cell index (7.40+/-0.5) in group 2 was significantly decreased from that in group 1 (14.03+/-0.82) (P<0.001 by Welch's method). The results suggest that NS-398, a selective COX inhibitor, has a chemopreventive activity against colon carcinogenesis without side-effects such as gastric ulceration.

Animals↗
PubMed1999

Beta-catenin (Ctnnb1) gene mutations in diethylnitrosamine (DEN)-induced liver tumors in male F344 rats.

Alterations in multiple phosphorylation sites on exon 3 of the beta-catenin gene have recently been implicated in hepatocarcinogenesis in humans as well as mice. To identify genetic alterations which could be involved in the chemical-induced hepatocarcinogenesis of rats, we analyzed the status of the sites in the beta-catenin gene (Ctnnb1) of liver neoplasms induced by diethylnitrosamine (DEN) in male F344 rats, using the polymerase chain reaction-single strand conformation polymorphism method. In the present investigation, we examined 35 hepatocellular neoplasms (28 adenomas and 7 carcinomas) for the expression of mutations in the region of the beta-catenin gene. Point mutation at codon 32, 35, 37 or 41, which has been reported in human and mouse liver cell carcinomas and/or other cancers, was recognized in eleven (31%) out of 35 lesions (8 adenomas and 3 carcinomas). Our results indicate that Ctnnb1 mutations may contribute to hepatocarcinogenesis in rats. Our finding that Ctnnb1 mutation was present in adenomas as well as carcinomas also suggests that the mutation is a relatively early event in DEN-induced hepatocarcinogenesis in rats.

Adenoma↗
PubMed1999

The telomerase activities in several organs and strains of rats with ageing.

Telomerase activity is known to be implicated both in cell immortalization and carcinogenesis. Telomerase activity has not been detected in most human somatic tissues. However, we previously confirmed that the activity is present both in methylazoxymethanol acetate-induced rat colonic adenocarcinoma and non-treated colonic mucosa, presumably indicating the tissue-specific activity of the enzyme in rats. To determine the standard activity of rat telomerase in various organs in relation to differences in sex, age and strain, we examined the activity by using the telomeric repeat amplification protocol (TRAP) assay. The testis, liver, and colon mucosa showed the activity. The brain had very low or negative activity in 5-week-old male rats of the F344, SD, Wistar, Donryu or ACI strains. Age (5-week-old and 9-month-old) or sex difference for the activity was not apparent in rats of these strains. In general, telomerase activity in the fetal brain, liver and kidney was stronger than in the adult organ. The telomerase activity of each organ was different from that of human. This difference may indicate that the rat has a specific mechanism for maintaining the telomeric repeats of the chromosome even in somatic tissues. The basic information resulting from this study may be useful for the study of the role of telomerase in tumorigenesis in animal experiment models.

Aging↗
PubMed1999

Suppressive effects of chlorogenic acid on N-methyl-N-nitrosourea-induced glandular stomach carcinogenesis in male F344 rats.

The modifying effects of chlorogenic acid (CA) on N-methyl-N-nitrosourea (MNU)-induced glandular stomach carcinogenesis were investigated in five groups of male F344 rats. Rats in Groups 1 through 3 were given MNU in drinking water at a concentration of 400 ppm for 12 weeks. Animals of Group 1 were then kept on the basal diet alone, and those of Group 2 or 3 were fed a diet containing 500 or 250 ppm CA for a subsequent 22 weeks. Group 4 was exposed to CA alone through the experimental period (36 weeks), and Group 5 was given the basal diet continuously and treated as a control. At the end of the experiment, the incidence of glandular stomach carcinoma of Group 3 was significantly smaller than that of Group 1 (p < 0.03). The incidence of adenomatous hyperplasia of Group 2 was also significantly lower than that of Group 1 (p < 0.02). In addition, the proliferating cell nuclear antigen (PCNA) labeling index of the epithelial cells from the non-neoplastic mucosa in rats of Group 2 or 3 was significantly smaller than that of Group 1 (p < 0.0001). These results suggest that CA has a chemopreventive effect on MNU-induced rat glandular stomach carcinogenesis by exposure during the post-initiation phase, and CA may be a promising agent for prevention of human stomach cancer.

Animals↗
PubMed1999

[The relationship between the histopathological atypia and expression of beta-catenin in colonic neoplasms resected by endoscopy; comparison with that of p53 protein].

Previous studies have reported predominantly nuclear localization of beta-catenin as a role for colorectal carcinogenesis. In this study, we examined the immunohistochemical expression of beta-catenin and p53 protein in 90 colonic neoplasms {33 carcinomas in adenoma (CIA), 28 high grade adenomas and 29 low grade adenomas}, resected by colonic endoscopy. Out of 33 CIAs. 28 (84.8%) cases showed predominantly nuclear localization of beta-catenin, and that was significantly higher than those of both high grade (46.4%) and low grade (13.8%) adenomas. The positiveness of p53 expression in CIAs was 51.5% (17/33), while 17.9% in high grade and 3.4% in low grade adenomas. However, there was no correlation between both protein expressions (p = 0.3472, chi 2 test). The results suggests that nuclear localization and accumulation of beta-catenin is earlier event than that of p53 mutation in adenoma-carcinoma sequence, and is useful as a marker in histopathological diagnosis for malignant conversion as well as p53.

Adenoma↗