Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 235 records · Page 13Linked to original sources

PubMed1997

Somatic mutation of the tuberous sclerosis (Tsc2) tumor suppressor gene in chemically induced rat renal carcinoma cell.

PURPOSE: von Hippel-Lindau (VHL) gene mutations are detected in noninherited, sporadic human renal cell carcinomas (RCs) at a high frequency. We recently identified a germline mutation in the rat homologue of the human tuberous sclerosis (TSC2) predisposing RC gene in the Eker rat model, and in this study we searched for mutations of the Tsc2 gene in chemically induced non-Eker rat RCs. MATERIALS AND METHODS: Chemically [N-ethyl-N-hydroxyethylnitrosamine (EHEN)]-induced non-Eker rat RC lines (designated as BP13 and BP36B) were subjected to PCR-single strand conformation polymorphism (PCR-SSCP) analysis using specific primers covering entire exons of Tsc2 gene (41 coding exons and one non-coding exon). We simultaneously searched for mutations of Vhl gene, a rat homologue of von Hippel-Lindau disease gene (VHL) as well as Tsc2 gene. RESULTS: BP36B showed an abnormal mobility shift from the normal tissue of the same rat in exon 35 on analysis by PCR-SSCP. This mutation was confirmed by direct sequencing and found to be a T-to-C transition at the second position of codon 1470, resulting in an amino acid change from leucine to proline (missense mutation). CONCLUSIONS: This is the first demonstration of Tsc2 gene somatic mutation in non-Eker rat RCs. Our present findings call attention to further investigation of the role of Tsc2 gene mutations in rat renal carcinogenesis and possible Tsc2 gene mutations in human RCs, especially of the non-clear cell type, which are not related to the VHL gene.

Animals↗

PubMed1997

Triazine derivatives inhibit rat hepatocarcinogenesis but do not enhance gap junctional intercellular communication.

We report here novel candidate chemopreventive agents active against experimental hepatocarcinogenesis. The triazine derivatives 6-(2-chlorophenyl)-2,4-diamino-1,3,5-triazine (2CPDAT), 6-(3-chlorophenyl)-2,4-diamino-1,3,5-triazine (3CPDAT), 6-(4-chlorophenyl)-2,4-diamino-1,3,5-triazine (4CPDAT), 6-(4-pyridyl)-2,4-diamino-1,3,5-triazine (PyDAT), and 6-(pyridine N-oxid-4-yl)-2,4-diamino-1,3,5-triazine (PyNODAT), synthesized in our laboratory, in addition to 6-(2,5-dichloro-phenyl)-2,4-diamino-1,3,5-triazine (DCPDAT), or irsogladine, which is a widely used anti-ulcer drug, were investigated for potential chemopreventive effects in a rat liver medium-term bioassay system. A significant inhibitory influence on enzyme-altered liver foci was found for 2CPDAT, 3CPDAT, 4CPDAT, and PyNODAT, but not for DCPDAT or PyDAT. The involvement of gap junctional intercellular communication in the inhibition was studied, but no change in gap junctional intercellular communication capacity in rat liver cells in vitro or in gap junction protein (connexin 32) expression in rat liver in vivo was noted. These results indicate that, although these irsogladine analogues exert inhibitory effects on rat liver carcinogenesis, their action is independent of modification of gap junctional intercellular communication.

Animals↗

PubMed1997

Differential dose-dependent effects of alpha-, beta-carotenes and lycopene on gap-junctional intercellular communication in rat liver in vivo.

In order to examine the relevance of alteration of gap-junctional intercellular communication (GJIC) to chemopreventive activity against carcinogenesis, the effects of alpha- and beta-carotene as well as lycopene, typical chemopreventive carotenoids, on cell coupling via gap junctions in rat liver in vivo were studied using a direct functional dye-transfer technique. We found that all three test compounds given at a dose of 50 mg/kg-body weight (b.w.) daily, 5 times by gavage, inhibited GJIC, while similar treatment with 5 mg/kg b.w. caused enhancement, especially in the beta-carotene- and lycopene-treated groups. At the dose level of 0.5 mg/kg b.w., the three compounds had no effect. The findings show that all three agents differentially modulate GJIC depending on the dose, with beneficial effects on cell communication only detected at the one dose. The result suggests that determination of the dose of chemicals to be used is crucial for human intervention studies.

Animals↗

PubMed1997

Demonstration of ras and p53 gene mutations in carcinomas in the forestomach and intestine and soft tissue sarcomas induced by N-methyl-N-nitrosourea in the rat.

The presence of ras family and p53 gene mutations in rat forestomach, intestine and liver tumors and soft tissue sarcomas induced by N-methyl-N-nitrosourea (MNU) was examined using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by direct sequencing analysis. In the forestomach squamous cell carcinomas (SCC), Ha-ras and p53 mutations were detected in 2 (40%) and 4 (80%) of 5 cases, respectively. The figures for Ki-ras and p53 gene mutations in adenocarcinomas of the large and small intestines were 3 (18.8%) and 5 (31.3%) of 16 cases. Soft tissue sarcomas in different sites were found to have mutations of Ki-ras in 7 (23.3%) and of p53 in 9 (30%) of 30 cases. One forestomach SCC and 2 soft tissue sarcomas had double p53 mutations in different exons. Single cases of forestomach SCC and intestinal adenocarcinoma had mutations in both Ki-ras and p53 genes. No mutations were found in counterpart benign tumors or hepatocellular adenomas. The p53 mutation spectrum revealed preferential clustering within exon 8 for the forestomach SCCs, and exons 5 and 8 for the intestinal adenocarcinomas, whereas the distribution was evenly spread through exons 5 to 8 in soft tissue sarcomas. All the detected ras or p53 mutations were G:C to A:T transitions. These results indicate firstly that specific Ki-ras, Ha-ras and p53 gene mutations in MNU-induced lesions are related to particular alkylation sites (G:C to A:T transitions) and secondly, although not essential, Ki-ras, Ha-ras or p53 gene mutations may be involved in the progression stage of forestomach, intestine and soft tissue neoplasms induced by MNU.

Adenocarcinoma↗

PubMed1997

Immunoreaction at 43 kDa with anti-ubiquitin antibody in breast neoplasms.

Protein ubiquitination has been implicated in ATP-dependent protein turnover and normal cell proliferation. To investigate whether the ubiquitin-mediated system is functionally involved in the cancerous state, we examined changes in protein ubiquitination in 52 surgically resected primary breast tumors. Immunohistochemically, ubiquitin (Ub) was identified in the cytoplasm of cancer cells, which were stained more strongly than adjacent normal ductal epithelium. Corresponding immunoblot analysis of normal and neoplastic regions of human breast showed that the immunoreaction for Ub at about 43 kDa was increased in all of the tumors (100%), regardless of the clinical stage or histologic grade. This protein, which gave a single spot on two-dimensional gel electrophoresis, had partial amino acid sequences which were identical to those of actin family members. Our results suggest that ubiquitination of this 43-kDa protein may be involved in the carcinogenesis or biological characteristics of human breast neoplasms.

Amino Acid Sequence↗

PubMed1997

Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats.

The influence of bovine lactoferrin (bLF) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). Following three weekly injections of AOM, the animals received 2 or 0.2% bLF for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2% and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control value (P < 0.01 and P < 0.05, respectively). The results indicate that bLF might find application for chemoprevention of colon cancer.

Adenocarcinoma↗

PubMed1997

Fibrotic focus in invasive ductal carcinoma of the breast: a histopathological prognostic parameter for tumor recurrence and tumor death within three years after the initial operation.

We investigated whether the presence of a fibrotic focus (FF) in the primary lesion and in lymph node metastasis is a good predictor of early tumor recurrence or death in patients with invasive ductal carcinoma (IDC). Multivariate relative risk (RR) of tumor recurrence and death according to the presence of FF in the primary tumor was estimated using the Cox proportional hazards regression model with adjustment for other prognostic factors (histologic grade, T classification, nodal status, tumor necrosis, DNA ploidy, c-erbB-2 protein expression, p53 protein expression, and labeling index of proliferating cell nuclear antigen). For the evaluation of the metastatic status in the axillary lymph nodes, RR of multivariate analysis was adjusted for the presence of FF in the metastatic tumor and the number of lymph nodes involved (1-3 and > 3). The presence of FF increased the RR of tumor recurrence significantly for the cases in all stages, and especially for those in stages I and II (RR = 6.9, P < 0.05 and RR = 25.0, P < 0.005, respectively). All cases that died of disease had FF. Among IDCs with FF, 24 cases had FF in lymph node metastasis. Significantly higher RRs of tumor recurrence and death were observed in cases with FF in lymph node metastasis than in those without it (RR = 2.0, P < 0.001 and RR = 5.9, P < 0.05, respectively). It was suggested that the presence of FF is an important predictor of early tumor recurrence or death in patients with IDCs. The presence of FF in lymph node metastatic lesions is also a significant prognostic parameter.

Adult↗

PubMed1997

Clinicopathological characteristics of primary breast cancer in older geriatric women: a study of 39 Japanese patients over 80 years old.

The number of primary breast cancers occurring in elderly women is increasing in Japan. Optimization of treatment regimens in this age group requires precise evaluation of the biological aggressiveness of these tumors as well as the performance status and extent of tumor spread. In 39 breast cancer patients who were at least 80 years old, we examined several parameters; the form of surgical therapy, the lymph node status, presence or absence of distant metastases, the histological type and grade of atypia, and overexpression of the c-erbB-2 oncoprotein in the cancer cells. They were correlated with the clinical outcome of the patient. Of the 33 patients who underwent a mastectomy and axillary lymph node dissection, five died from cancer recurrence. Only one out of 22 patients without lymph node metastases died from cancer, while four out of the eight patients with metastases to three or more lymph nodes died from cancer recurrence within 2.7 years of surgery. The overall survival curves also differed between patients with low-risk histological tumors or grade 1 or 2 invasive ductal carcinoma and those with grade 3 invasive ductal/lobular carcinoma. Overexpression of c-erbB-2 also affected survival. Regional recurrence occurred in three out of the six patients for whom only lumpectomy or simple mastectomy was performed. These results indicate that, although primary breast cancer occurring in patients over 80 years old was largely of low-grade malignancy, patients with three or more lymph node metastases, invasive ductal/lobular carcinomas of grade 3, or c-erbB-2 overexpression frequently exhibited an aggressive clinical course.

Aged↗

PubMed1997

Carcinogenicity of methylurea or morpholine in combination with sodium nitrite in rat multi-organ carcinogenesis bioassay.

For carcinogenic risk assessment of combinations of N-nitroso precursors in man, the effects of feeding methylurea (MU) or morpholine (Mor) plus sodium nitrite (NaNO2) were investigated using a multi-organ carcinogenesis model. In experiment 1, to initiate multiple organs, groups of 10 or 20 male F344 rats were treated with 6 carcinogens targeting different organs. Starting a week after completion of this initiation phase, animals were given 0.1% MU or 0.5% Mor in their food and/or 0.15% NaNO2 in their drinking water for 23 weeks. The induction of tumors and/or preneoplastic lesions in the forestomach and esophagus was significantly increased in the group receiving MU plus NaNO2. The numbers and areas of liver glutathione S-transferase placental form (GST-P)-positive foci were significantly elevated with MU or Mor plus NaNO2. Experiment 2 was conducted to assess formation of N-nitroso compounds in the stomach, and to detect DNA adduct generation in target organs by immunohistochemical staining. Groups of 5 or 14 animals were starved overnight, then given 0.4% MU or 2.0% Mor in the diet, or basal diet alone for 1 h. Then NaNO2 or distilled water was given intragastrically. The mean gastric N-methyl-N-nitrosourea yield in the MU plus NaNO2 group was 7700 micrograms at 2 h after combined administration. The mean N-nitrosomorpholine yield in the group given Mor plus NaNO2 was 6720 micrograms. Immunohistochemically, N7-methyldeoxyguanosine-positive nuclei were evident in the forestomach epithelium at 8 h after the combination treatment with MU plus NaNO2.

Administration, Oral↗

PubMed1997

Solitary esophageal metastasis of breast cancer with 15 years' latency: a case report and review of the literature.

A 68-year-old woman with a history of breast and colon cancer at the ages of 48 and 65 years, respectively, who presented with dysphagia is described. An upper gastrointestinal series and endoscopic examination revealed a circumferential stricture without ulceration in the middle-third area of the esophagus. Computed tomography demonstrated a submucosal tumor in the esophageal wall. A biopsy specimen obtained from the mucosa overlying the tumor revealed poorly differentiated adenocarcinoma, suggesting metastasis from the previous breast cancer. Subtotal esophagectomy with reconstruction was performed. Macroscopically, a submucosal tumor measuring 2.0 x 1.7 cm was observed in the resected esophagus. Microscopic examination revealed poorly differentiated adenocarcinoma, which was quite similar histologically to the breast cancer resected 15 years previously. Enzyme immunoassay and immunohistochemical analyses of the resected tumor revealed positivity for both estrogen and progesterone receptor, confirming the diagnosis of a metastatic cancer from the previous breast tumor.

Adenocarcinoma↗

PubMed1997

Continuous local injection of carboplatin into the uterine cervix for cervical and endometrial cancer: preliminary study.

Platinum compounds are thought to be concentration- and time-dependent, but intravenous (i.v.) administration does not afford prolonged high platinum concentration in tumor tissue. In order to examine the influence of long-term local continuous (LC) injection of carboplatin, a pharmacokinetic study was performed. Twenty-six patients with uterine cancer were included. I.v. administration (11 patients): carboplatin (210 mg) was given i.v. and samples of target tissue were obtained at operation about 2 or 24 h after administration. LC administration (15 patients): the 21-gauge needle was implanted at the uterine cervix, and carboplatin was injected continuously (30 mg/day) for 3, 7 or 14 days using an external pump. The tissue platinum concentration was measured in the pelvic organs. The mean platinum levels at the cervix and vaginal wall in the LC (7 days) group were higher than those in the i.v. (2 h) group (p < 0.01). With LC injection, sustained platinum levels were maintained in the pelvic organs for a long time, with very few side effects. LC injection may be advantageous on the basis of pharmacokinetics.

Adult↗

PubMed1997

Raman spectroscopy in dental research: a short review of recent studies.

The Raman spectroscopic technique enables us to obtain vibrational (IR and far-IR) spectra of minerals by analyzing scattered light caused by (visible or near-visible) monochromatic laser excitation. The method possesses several advantages over IR absorption, including simple sample preparation, easy spectral/band analysis, and linear-response to mineral/chemical concentrations. In micro-Raman spectrometer systems, samples are positioned under an optical microscope, and specimens can be scanned with a lateral resolution (approximately 1 mm). In this paper, recent applications of micro-Raman spectroscopy and near-infrared Fourier transform Raman spectroscopy in the study of dental hard tissues and of calculus are reviewed. Special attention is given to mineral components in enamel, dentin, and calculus, and to calcium fluoride formed in/on enamel. The results from the use of an Ar(+)-laser/grating-based micro-Raman spectrometer show that: CaF2 formed in/on enamel by APF treatment is detectable and different from pure CaF2; and with the technique, the crystallite orientation in enamel can be determined. A Raman spectrometer based on Fourier transform and a diode-laser-pumped Nd:YAG laser (1.06 mm) can be used to obtain fluorescence-free Raman signals from biological materials, and identification of mineral components present in dental calculus is possible.

Calcium Fluoride↗

PubMed1997

The use of cyclosporin-A in the treatment of virus-associated hemophagocytic syndrome in adults.

Virus-associated hemophagocytic syndrome (VAHS) is one of the categories of hemophagocytic syndrome (HPS) which is a clinicopathologic entity characterized by systemic proliferation of benign hemophagocytic cells of the monocyte-macrophage-histiocyte lineage, associated with fever, cytopenia, hepatosplenomegaly, lymphadenopathy, and coagulopathy. The disease affects children and adults after infection with various viruses. However, clinical manifestations are quite different between children and adults. Although the etiology of VAHS is not fully understood, accumulating evidence has revealed dysregulation of the immune system. Standard treatment of VAHS has not been established, yet, but successful trials aiming at immunomodulation have been reported. In this report, current concepts and clinical features of VAHS are reviewed, focusing on the recently introduced cyclosporin A therapy in VAHS in adults.

Adult↗

PubMed1997

Preoperative assessment of myometrial invasion of endometrial cancer by MR imaging and intrauterine ultrasonography with a high-frequency probe: preliminary study.

This study was undertaken to assess the capabilities of intrauterine ultrasonography performed while inflating the endometrial cavity with fluid and magnetic resonance imaging as a means to assess the depth of myometrial invasion by endometrial cancer preoperatively. Twenty women with endometrial disorders underwent preoperative intrauterine ultrasonography and magnetic resonance imaging. We introduced the probe and hysteroscope simultaneously into the uterine cavity and observed both the uterine cavity surface and cross-sectional uterine muscle. We classified the depth of myometrial invasion as none, superficial (less than half of the myometrium), or deep (more than half of the myometrium). The accuracy of magnetic resonance imaging and intrauterine ultrasonography in assessing the depth of myometrial invasion was 85%. In two cases, intrauterine sonography was able to demonstrate superficial myometrial invasion that could not be diagnosed by magnetic resonance imaging. In contrast, intrauterine ultrasonography was unable to diagnose myometrial invasion in two cases in which magnetic resonance imaging could diagnose it. Intrauterine sonography may be useful for estimation of myometrial invasion of endometrial cancer.

Adult↗

PubMed1997

A hidden immunoglobulin G2 in patients with rheumatoid arthritis detected by nuclear magnetic resonance.

OBJECTIVE: The ratios of immunoglobulin (Ig) G1 and IgG2 in patients with rheumatoid arthritis (RA) were examined by nuclear magnetic resonance (NMR) and the results were compared to data obtained by ELISA. METHODS: The IgG of 11 patients with RA were prepared with a DE-52 column and the specific signals for IgG1 and IgG2 were measured by NMR. The ratios of IgG1 and IgG2 were determined by the intensity of this signal. The samples were also measured by ELISA. RESULTS: The ratios of IgG2 in patients with RA measured by NMR were increased significantly compared to controls. However, there were no significant differences in the data determined by ELISA. Thus, a discrepancy exists in the analysis of IgG2 ratios between NMR and ELISA methods. CONCLUSION: There was a discrepancy in the IgG2 ratios of patients with RA between NMR and ELISA methods, and we attribute this to a conformational difference in IgG2 in patients with RA.

Adult↗

PubMed1997

[High fever during the treatment of acute promyelocytic leukemia with all-trans retinoic acid].

A 56-year-old woman was admitted for evaluation of petechiae and acute promyelocytic leukemia was diagnosed. Administration of all-trans retinoic acid (ATRA) at 60 mg per day was begun. On the same day, high fever was recognized. There was no evidence of infection nor other organ dysfunction. Administration of steroid caused a resolution of the fever. The same phenomenon was observed three times subsequently. High fever was the adverse reaction in this patient during the treatment of ATRA, and steroid was dramatically effective.

Anti-Inflammatory Agents↗

PubMed1997

Detection of numerical and structural alterations and fusion of chromosomes 16 and 1 in low-grade papillary breast carcinoma by fluorescence in situ hybridization.

Intracystic papillary breast tumors, including intraductal papilloma and low-grade intracystic papillary carcinoma, constitute a group for which differential diagnosis is frequently difficult. We examined the status of chromosomes 16 and 1 by multicolor fluorescence in situ hybridization (FISH) analyses and the DNA ploidy patterns by flow cytometry in 26 intracystic papillary tumors. Alterations of chromosomes 16 and 1 were detected by FISH in 93 and 85%, respectively, of 14 low-grade papillary carcinomas, and the latter alterations always concurred with the former. Two-color FISH using probes for the D1Z1 (1q12) and D16Z2 (16cen) loci or the D1Z1 and D16Z3 (16q11) loci showed that fusion of chromosomes 16 and 1, mostly with breakpoints distal to 16q11.2 and proximal to 1q12, occurred in 77% of the papillary carcinomas. DNA aneuploidy was detected in 6% of these carcinomas. No papilloma showed these chromosome alterations or DNA aneuploidy. Chromosome 16 and 1 fusions appeared to occur frequently in diploid breast carcinomas and to be involved in the acquisition of a malignant phenotype by duct epithelial cells. We suggest that two-color FISH methods for detecting 1;16 fusions might be applicable as supportive methods for the differential diagnosis of intracystic papillary breast tumors.

Artificial Gene Fusion↗

PubMed1997

[A case of lung carcinoid].

A 78-year-old female was pointed out an abnormal shadow in left lung field. For 4 years this shadow was followed up as benign tumor. Chest CT scan revealed growing tumor and new tumor in right lung. Tumor resection was performed. Until operation time carcinoid syndrome was not found. This case was diagnosed histopathologically typical carcinoid of peripheral lung.

Aged↗