Biomedical subjects

K Kanazawa

Publications and source records attributed to K Kanazawa.

At least 55 records · Page 3Linked to original sources

PubMed2000

Detection of biomarkers for apoptosis in rat liver after perfusion with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1).

We previously demonstrated that 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) induced apoptosis in primary cultured rat hepatocytes. In this study, we investigated apoptotic biomarkers in rat liver after perfusion with 30 microM Trp-P-1 as preliminary experiments for in vivo study. Induction of c-Myc and p53 protein and the activities of caspase-3, -6, and -8 were detected in Trp-P-1-perfused liver. In addition, Trp-P-1 modulated the DNA binding activity of the apoptosis-related transcription factors, NF-kappaB and AP-1. These results imply a possibility that Trp-P-1 would induce apoptosis in vivo.

Animals↗

PubMed2000

Dietary antioxidants fail in protection against oxidative genetic damage in in vitro evaluation.

Carcinogenesis is believed to be induced through the oxidative damage of DNA, and antioxidants are expected to suppress it. So, the polyphenolic antioxidants in daily foods were investigated to see whether they protect against genetic damage by active oxygen. In the evaluation, we used a bioassay and a chemical determination, a Salmonella mutagenicity test for mutation by a N-hydroxyl radical from one of the dietary carcinogens 3-amino-1-methyl-5H-pyrido[4,3-b]indole and the formation of 8-hydroxyl (8-OHdG) from 2'-deoxyguanosine (2'-dG) in a Fenton OH-radical generating system. Thirty-one antioxidants including flavonoids were compared in terms of radical-trapping activity with bacterial DNA and 2'-dG. Antioxidants inhibited the mutation but the IC50 values were in the mM order. Against 8-OHdG formation, only alpha-tocopherol had a suppressive effect with an IC50 of 1.5 microM. Thus, except alpha-tocopherol, the dietary antioxidants did not scavenge the biological radicals faster than bacterial DNA and intact 2'-dG, indicating that they failed to prevent oxidative gene damage and probably carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2000

Pleomorphic carcinoma of the pancreas with massive lymphocytic stromal infiltration and long-term survival after resection.

BACKGROUND: Pleomorphic carcinoma of the pancreas is a rare tumor with an extremely poor prognosis. The mean survival time is reported to be approx 3 mo. CLINICAL AND HISTOLOGICAL FINDINGS: A 56-yr-old Japanese man presenting with general fatigue, loss of weight, and high fever was found to have a large hypervascular mass in the body of the pancreas with regional lymph node metastases. Laboratory investigation revealed leukocytosis, elevated erythrocyte sedimentation rate (ESR), and high serum C-reactive protein (CRP). In addition to distal pancreatectomy, splenectomy and lymph node dissection were performed. Histology showed the presence of pleomorphic large cells with bizarre mono- or multinuclei, growing in sarcomatoid pattern without mutual cohesiveness. Another noticeable finding was massive lymphocytic infiltration of the stroma of the neoplasm. Immunohistochemically, the infiltrating lymphocytes consisted of cytotoxic type of T cells. In addition, in situ hybridization for Epstein-Barr virus-encoded RNA (EBAR-1) was not seen in the tumor cells or in lymphocytes. After surgery the patient did not undergo chemotherapy or radiotherapy. He has been well without recurrence for 8 yr. CONCLUSION: We report a case of pleomorphic carcinoma, possibly lymphoepithelioma-like carcinoma, of the pancreas with massive lymphocytic stromal infiltration and long-term survival after resection. Cytokine responses and cellular immunoreactivity may have contributed to a long-term survival, which is unusual in the common type of pleomorphic carcinoma of the pancreas.

Carcinoma↗

PubMed2000

Synergistic effects of food colors on the toxicity of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) in primary cultured rat hepatocytes.

The synergistic effect of food additives or food colors on the toxicity of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was investigated using primary cultured rat hepatocytes. When hepatocytes from rats fed a standard diet were treated with a mixture of four major food additives (sorbitol, sodium L(+)-glutamate, benzoic acid, and propylene glycol) or a mixture of six typical artificial food colors (erythrosine, allura red, new coccine, brilliant blue, tertrazine, and fast green), the in vitro treated food-color mixture itself showed cytotoxicity: the reduction of cell viability and decreases in the activities of gluconeogenesis and ureogenesis. The food-color mixture enhanced cytotoxicity of Trp-P-1 obviously. We then investigated the effects of in vivo-dosed food additives or food colors on Trp-P-1-caused toxicity. Hepatocytes were isolated and cultured from rats fed a diet containing a mixture of food additives or a mixture of food colors with half the amount of their respective acceptable daily intake for 4 wk. Trp-P-1 was administered to the hepatocytes at various concentrations for 12 h. Synergistic effects of in vivo-dosed food additives and food colors were not observed on Trp-P-1-caused cytotoxicity as estimated by a loss of cell viability and the reductions of DNA and protein syntheses. On the contrary, we have observed that in vivo administered food colors synergistically facilitated to reduce the activities of gluconeogenesis and ureogenesis in Trp-P-1-treated hepatocytes. These results suggest that the daily intake of artificial food colors may impair hepatic functions such as gluconeogenesis and ureogenesis, when dietary carcinogens are exposed to the liver cells.

Animals↗

PubMed2000

Low serum cholesterol levels and depressive state in human dock visitors.

OBJECTIVE: The purpose of the present study was to investigate an association between serum cholesterol levels and depressive state. METHOD: Physical examinations and mental assessments were performed for 13702 human dock visitors. We obtained 13571 sets of complete data for serum total cholesterol, the scores for depressive state and possible confounders such as sex, age, body weight, body mass index (BMI), recent weight loss, total protein and concomitant medical diagnoses. RESULTS: Their depressive state varied significantly across the serum cholesterol levels after adjusting age and gender. After controlling all the above confounding variables the significance still remained, not only in the categorical analysis but also in the continuous analysis. CONCLUSION: The present findings suggest that there is an association between cholesterol and depressive state.

Adult↗

PubMed2000

[Antipseudomonal activity of carbapenem antibiotics].

To date, three carbapenem antibiotics have been introduced for clinical use, and they can be structurally classified into two types. One is a natural type that has the naturally-occurring carbapenem skeleton and a strongly basic (cationic) moiety in the C-2 side chain, like imipenem or panipenem. The other is a new generation carbapenem, meropenem, which has the 1 beta-methyl carbapenem skeleton and a less basic group in the C-2 side chain. It was reported that there were some significant differences among these two types of carbapenems concerning the antimicrobial profile, especially the antipseudomonal activity. Since Pseudomonas aeruginosa was one of the target pathogens of carbapenem antibiotics, these facts prompted us to overview the different mode of action among imipenem, panipenem and meropenem and clarify the structure-activity relationships of carbapenems with regard to the antipseudomonal activities. In this article, we discuss that both the chemical structure and the physicochemical properties of carbapenems greatly influence a variety of antipsedomonal actions including MIC, affinity for PBPs, outer membrane permeability, interaction with various beta-lactamases and multidrug efflux systems etc., and that the cationic center in the C-2 side chain plays an important role in antipseudomonal activities. This review will be helpful in developing new types of antipseudomonal carbapenems and/or new clinical applications of carbapenem antibiotics for treating pseudomonal infection.

Carbapenems↗

PubMed1999

Systemic endothelial function is preserved in men with both active and inactive variant angina pectoris.

To test the hypothesis that coronary spasm could be a coronary manifestation of systemic endothelial dysfunction and that the activity of coronary spasm could influence systemic endothelial function, we examined brachial flow-mediated, endothelium-dependent vasodilation and nitroglycerin-induced endothelium-independent vasodilation with high-resolution ultrasound in 11 men with variant angina pectoris (6 active and 5 inactive) without established coronary atherosclerosis. Endothelium-dependent vasodilation in peripheral circulation was preserved in men with active and inactive variant angina pectoris, suggesting that systemic endothelial dysfunction is not involved in either the pathogenesis or the activity of coronary spasm.

Aged↗

PubMed1999

Mutational analysis of the cardiac actin gene in familial and sporadic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) results in part from genetic disorders. Recently, missense mutations of the cardiac actin gene have been reported to cause DCM. We studied 136 Japanese DCM cases to elucidate how frequently the gene mutations are involved in its pathogenesis. Genomic DNA samples were obtained from 136 DCM cases (107 males, 29 females), containing 30 familial DCM (5 confirmed and 25 suspected). All six exons of the cardiac actin gene were analyzed by polymerase chain reaction, single-strand conformation polymorphism, and sequencing. We detected no mutations of the disease causation previously reported (G867A or A1014G) but two silent mutations (G979C and C1018T) in exon 6 and one point mutation (T1080A) in the 3'-untranslated region. As a result of screening 128 healthy subjects, these novel silent mutations were found to be mere genetic polymorphisms, not responsible for the disease. Although some genetic polymorphisms exist in the cardiac actin gene, mutations of the gene are rarely responsible for DCM, at least in the Japanese patients.

3' Untranslated Regions↗

PubMed1999

Combination effects of tamoxifen plus 5-fluorouracil on gastric cancer cell lines in vitro.

We tested the effect of tamoxifen alone and tamoxifen plus 5-fluorouracil (5-FU) on proliferation of two different types of gastric cancer cell lines using the WST-1 method. A high dose of tamoxifen suppressed the proliferation of KATOIII cells (poorly differentiated adenocarcinoma), but MKN28 cells (well-differentiated adenocarcinoma) were not affected. The combination of the two drugs resulted in a synergistic anti-proliferative activity on KATOIII cells. On the other hand, in the combination therapy, tamoxifen stimulated MKN28 cells to proliferate in a dose-dependent manner. TGF-beta1 secretion was not changed in KATOIII cells by tamoxifen plus 5-FU treatment but was down-regulated in MKN28 cells. Both cancer cell lines were judged as intracellular estrogen receptor (ER) negative. These data suggest that the anti-proliferative effects of tamoxifen plus 5-FU on KATOIII cells were not dependent on ER expression or TGF-beta1 secretion. On the other hand, their proliferative effects on MKN28 cells might be, in part, caused by the reduced secretion of TGF-beta1.

Adenocarcinoma↗

PubMed1999

Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction.

BACKGROUND: Rupture of the fibrous cap of an atherosclerotic plaque is a key event that predisposes to acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) may contribute to weakening of the cap, which favors rupture. Stromelysin, a member of MMP family, is identified extensively in human coronary atherosclerotic lesions. It can degrade most of the constituents of extracellular matrix as well as activating other MMPs, which suggests that it may play an important role in plaque rupture. Recently, a common variant (5A/6A) in the promoter of the stromelysin gene has been identified. The 5A/6A polymorphism could regulate the transcription of the stromelysin gene in an allele-specific manner. METHODS AND RESULTS: To investigate the relation between the 5A/6A polymorphism in the promoter of the stromelysin gene and AMI, we conducted a case-control study of 330 AMI patients and 330 control subjects. The prevalence of the 5A/6A+5A/5A genotype was significantly more frequent in the patients with AMI than in control subjects (48.8% vs 32.7%, P<0.0001). In logistic regression models, the odds ratio of the 5A/6A+5A/5A was 2.25 (95% CI, 1.51 to 3.35). The association of 5A/6A polymorphism with AMI was statistically significant and independent of other risk factors. CONCLUSIONS: The 5A/6A polymorphism in the promoter of the stromelysin gene is a novel pathogenetic risk factor for AMI.

Alleles↗

PubMed1999

Identification of a novel gene, OASIS, which encodes for a putative CREB/ATF family transcription factor in the long-term cultured astrocytes and gliotic tissue.

Gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system (CNS). To study the mechanisms underlying gliosis, we performed differential display screening for genes specifically induced in long-term cultured astrocytes used as an in vitro gliosis model. We identified and characterized a gene (named OASIS, for old astrocyte specifically-induced substance) expressed in long-term cultured mouse astrocytes, or 'old astrocytes (OA)'. The OASIS gene encoded a putative transcription factor belonging to the cyclic AMP responsive element binding protein/activating transcription factor (CREB/ATF) gene family, with homology to box B-binding factor-2 (BBF-2), a Drosophila transcription factor. Its expression was developmentally regulated; OASIS mRNA was primarily expressed in the salivary gland and cartilage in the mouse embryo and it was transiently upregulated in the brain during postnatal two weeks. The expression became weaker in the adult brain. We also demonstrated that an expression of the OASIS mRNA was induced in response to the cryo-injury of the mouse cerebral cortex. The distribution pattern of the OASIS-positive cells in the injured cortex was very similar to that of the glial fibrillary acidic protein (GFAP)-positive cells. These results suggest that OASIS protein may play a role in gliotic events.

Activating Transcription Factors↗

PubMed1999

The significance of microsatellite instability in predicting the development of metachronous multiple colorectal carcinomas in patients with nonfamilial colorectal carcinoma.

BACKGROUND: Patients with metachronous multiple colorectal carcinomas have been reported to have a higher frequency of a family history of colorectal carcinoma, associated colorectal adenomas, and extracolonic malignancies. These clinicopathologic factors also are considered to be related to the development of metachronous multiple colorectal carcinomas after surgery for colorectal carcinoma. In this article, the authors investigated whether genetic markers such as microsatellite instability (MSI) were helpful in predicting the development of metachronous multiple colorectal carcinomas. METHODS: Between 1990-1997, 312 colorectal carcinoma patients underwent yearly surveillance colonoscopy after surgery. Among these patients, there were 19 with nonfamilial colorectal carcinoma in whom metachronous multiple colorectal carcinomas were diagnosed during the yearly surveillance colonoscopy. A control group was comprised of 28 patients who did not demonstrate either synchronous or metachronous carcinomas over a period of > or =5 years. Six microsatellite markers (D2S123, D3S1029, D3S1611, TP53, Mfd26, and Mfd36) were used to determine MSI by polymerase chain reaction. RESULTS: The frequency of MSI positive cases was significantly higher in patients with sporadic metachronous multiple colorectal carcinomas than in those with a single carcinoma (17/19 [89%] vs. 4/28 [14%]; P<0.0001). In tumors occurring in the distal colon and rectum, the percentage of MSI positive carcinomas was significantly higher in the patients with metachronous multiple carcinomas than in those with a single carcinoma (13/15 [87%] vs. 0/19 [0%]; P<0.0001). No such difference was observed in the proximal colon. CONCLUSIONS: Based on the findings of the current study, the analysis of MSI in sporadic carcinomas of the distal colon and rectum may be helpful in predicting the development of metachronous multiple colorectal carcinomas.

Colonoscopy↗

PubMed1999

Eos: a novel member of the Ikaros gene family expressed predominantly in the developing nervous system.

We identified a novel member of the Ikaros gene family, which has critical roles in the development of lymphoid lineages. This gene, which we named Eos, was expressed predominantly in the developing central and peripheral nervous system. Eos protein could interact with itself and Ikaros protein through its C-terminal portion in the yeast two hybrid assay. These findings suggested that Eos may have important roles in neural development similarly to the Ikaros family in the development of hemolymphoid tissue.

Amino Acid Sequence↗

PubMed1999

Tumor diameter/volume and pelvic node status assessed by magnetic resonance imaging (MRI) for uterine cervical cancer treated with irradiation.

PURPOSE: To evaluate the prognostic value of tumor diameter/volume and pelvic node status assessed by magnetic resonance imaging (MRI) in patients with uterine cervical cancer treated with radiation therapy. METHODS AND MATERIALS: Forty-four patients with intact uterine cervical squamous carcinoma treated with a combination of external irradiation and high-dose-rate intracavitary therapy were analyzed. Actuarial disease-free survival (DFS), pelvic control rate (PC), and distant metastasis-free rate (DMF) were analyzed by tumor diameter, volume, and pelvic node status assessed by pretreatment MRI. RESULTS: Anteroposterior (AP) and lateral (RL) tumor diameter significantly affected DFS. The 2-year DFS was 74% for patients with < 40 mm in AP diameter tumor, and 24% for > or = 40 mm tumor (p = 0.02). Whereas PC was not influenced, DMF was significantly affected by AP tumor diameter. Tumor volume did not significantly affect any endpoints. Patients with enlarged pelvic nodes had significantly poorer outcome compared to those with none on PC, DMF, and DFS. The 2-year DFS was 78% for node-negative, and 10% for node-positive patients (p = 0.0001). CONCLUSION: AP tumor diameter and pelvic lymph node status assessed by MRI were the significant prognostic factors in uterine cervical cancer treated with irradiation. Prognostic value of tumor volume should be reassessed prospectively with an appropriate imaging technique. AP tumor diameter predominantly affected the incidence of distant metastasis, and lymph node status affected both pelvic control and distant metastasis.

Adult↗

PubMed1999

The validity and significance of substage IIIC by node involvement in epithelial ovarian cancer: impact of nodal metastasis on patient survival.

OBJECTIVE: The aim of this study was to examine whether there is a possible difference in patient survival (1) between node-positive and node-negative groups for Stage I, II, IIIA+B, and IIIC disease and (2) between node-positive Stage I through IIIB disease and Stage IIIC disease. METHODS: Medical records of 125 patients with Stage I, II, and III epithelial ovarian cancer were retrospectively analyzed for clinical and histological characteristics with special reference to node-positive or -negative status, and patient survival by lymph node status was compared for FIGO intraperitoneal stage. RESULTS: One hundred eleven of 125 patients were explored for retroperitoneal and inguinal nodes and divided into a node-positive group [n = 35 (31.5%)] and a node-negative group [n = 76 (68.5%)]. Stage III disease and histological grade 3 disease were significantly more frequent in the node-positive group in comparison with the corresponding figures in the node-negative group (P = 0.0007 and P = 0.0005). The 10-year survival was not significantly different between the node-positive and the node-negative group for each of Stage I, II, IIIA+B, and IIIC disease. However, survival was considerably worse in the node-positive group compared to that in the node-negative group for each of Stage I and II disease, and was significantly worse for Stage I+II disease (P = 0.0172). The survival was significantly worse in the node-positive group compared to that in the node-negative group also for Stage I through IIIB disease taken as a whole (P = 0.0212), although not for Stage IIIA+B disease alone. On the other hand, patient survival of node-positive Stage I through IIIB disease, taken as a whole, was significantly better than that in Stage IIIC disease (P < 0.0001). CONCLUSIONS: It might not be valid, on the basis of patient prognosis, to group node-positive Stage I, II, and IIIA+B disease into a criterion of Substage IIIC together with Stage III disease of abdominal implants greater than 2 cm in diameter outside the pelvis. For further evaluation of the prognostic significance of node involvement, survivals should be compared among patients with de novo node disease, with node disease removed, and otherwise similar patients without node disease, ideally in a prospective randomized trial with a large number of patients.

Adult↗

PubMed1999

Muscle change after anal sphincter reinnervation by a normal somatic peripheral nerve: preliminary study.

INTRODUCTION: Pudendal neuropathy causes idiopathic fecal incontinence. We thus designed a new operation for idiopathic fecal incontinence based on the hypothesis that a conversion from innervation by the neuropathic pudendal nerve to that by the normal somatic peripheral nerve innervating a larger skeletal muscle might enable the anal sphincter to recover from neuropathic muscular atrophy. This study was undertaken to investigate the muscular change of the external anal sphincter after such an operation. METHODS: On 14 sides of eight dogs, the transected proximal end of the nerve innervating the biceps femoris muscle was microsurgically cross-transferred to the distal end of the transected pudendal nerve. The external anal sphincter was analyzed by electromyography and adenosine 5'-triphosphatase staining at three months after surgery. RESULTS: On 13 of 14 sides, the external anal sphincter was well preserved and the evoked potential was clearly recorded. The external anal sphincter in these dogs, however, had neither any basal electrical activity nor any increased electrical activity. The percentage of Type 1 muscle fibers of the external anal sphincter innervated by the nerve to the biceps femoris muscle (30.9 +/- 9.8 percent) was significantly higher than that of the normal external anal sphincter (15.2 +/- 8.5 percent; P < 0.001) and also significantly lower than that of the normal biceps femoris muscle (38.5 +/- 7.5 percent; P = 0.006). The diameter of the muscle fibers (Types 1 and 2) of the external anal sphincter (expressed as mean +/- standard deviation) innervated by the nerve to the biceps femoris muscle (32.9 +/- 6.2 microm) was also significantly larger than that of the normal external anal sphincter (29.9 +/- 5.1 microm; P = 0.021) and significantly smaller than that of the normal biceps femoris muscle (36.1 +/- 6.1 microm; P = 0.028). CONCLUSIONS: The cross-nerve transfer procedure in a dog model was found to prevent muscular atrophy of the external anal sphincter when performed immediately after pudendal nerve transection.

Anal Canal↗

PubMed1999

Intraoperative localization of colorectal tumors in the early stages using a marking clip detector system.

In laparoscopic colectomy the identification of the site of a tumor is often difficult. The topical injection of india ink or blue dye by preoperative colonoscopy is the most prevalent method to mark the tumor site; however, such a procedure also includes the intrinsic danger of possibly injecting dye into the peritoneal cavity. In addition, the injected marker may also spread so widely that the intended site may become obscure. A marking clip detector system was used to detect metallic marking clips in the luminal side that had been applied to the mucosa adjacent to the lesion during the course of preoperative colonoscopy. This method was able to identify the marked site in 40 percent of cases in which only one clip was applied to the mucosa. However, when the lesion sites were marked with two or three clips, then the detection rate increased to 100 percent. Based on our findings, this procedure was found to be a safe and reliable method for identifying lesions during laparoscopic-assisted colectomy.

Colectomy↗

PubMed1999

Prospective observation of small "flat" tumors in the colon through colonoscopy.

PURPOSE: No prospective observations of "flat" tumors of the colon have yet been reported. The purpose of this study was to investigate the progression of small flat tumors by prospective observations using colonoscopy. METHODS: The shapes of flat tumors were classified into three types, including slightly elevated lesions with a flat top (flat-top type), slightly elevated lesions with a wide depression in the center (wide-depressed type), and slightly elevated lesions with a slit-like depression in the center (slit-depressed type). A total of 14 flat tumors of the colon in 13 patients (2 women; median age, 58; range, 46-72 years) were examined in this project. All cases were followed up prospectively using colonoscopy, and all underwent a resection using the submucosal saline injection and snaring technique. RESULTS: Because two patients were eventually dropped from the follow-up, only 12 lesions were studied. The observation period ranged from 11 to 26 (median, 19) months. At the time the observations started, the diameter of the tumors varied from 2 to 6 (median, 4) mm, and the shapes were flat-top type in five lesions, wide-depressed type in three lesions, and slit-depressed type in four lesions. Of the 12 flat tumors, 8 showed various changes in their shape. However, only two lesions demonstrated an increase in diameter of the tumor from 2 to 4 mm. In the other ten tumors any change in size was less than 2 mm. No lesions were carcinomas according to the final histologic diagnosis, but all were adenomas. CONCLUSIONS: Flat tumors of the colon did not rapidly progress when they measured approximately 5 mm in diameter. Such flat tumors did tend to change their shapes; however, such changes did not indicate invasion to the submucosal layer.

Adenoma↗