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Biomedical subjects

T Nishida

Publications and source records attributed to T Nishida.

At least 217 records · Page 12Linked to original sources
PubMed1998

Significance of biologic aggressiveness and proliferating activity in papillary thyroid carcinoma.

Papillary thyroid carcinoma is a frequent thyroid cancer. Many factors have been reported to be of prognostic importance, but the significance of biologic factors suggesting aggressiveness and proliferating activity has not been sufficiently documented. Conventional prognostic factors such as age, extrathyroidal invasion, lymph node and distant metastasis, and biologic factors including histologic differentiation, DNA ploidy, S-phase and G2M-phase fractions, and expression of CD44 variant 6 (CD44-v6) obtained from 131 patients who underwent surgery for papillary thyroid carcinoma at Osaka Police Hospital were analyzed retrospectively. Age was closely related to extrathyroidal invasion, G2M-phase fraction, and CD44-v6 expression. Extrathyroidal invasion was independently related to age, gender, and lymph node metastasis. The grade of lymph node metastasis was related to extrathyroidal invasion, gender, distant metastasis, and CD44-v6 expression. Distant metastasis was associated with aneuploid tumors. Cause-specific survival was independently related to biologic factors including extrathyroidal invasion, distant metastasis, DNA ploidy and S-phase fraction. These results suggest that biologic factors indicating aggressiveness and proliferating activity are important for papillary thyroid carcinoma.

Aged↗
PubMed1998

Lazaroid U74500A is superior to U74006F in preserving rabbit heart for 24 hours.

BACKGROUND: Lazaroid, a series of 21-aminosteroids, has been shown to reduce free-radical-mediated injury after ischemia and reperfusion. Recent in vitro studies have demonstrated that, among the various compounds studied, the most efficient agent was U74500A. The question is whether these findings apply to the whole heart experiencing ischemia-reperfusion injury. In this study we compared the myocardial protective effects of U74006F, the only clinical candidate, and U74500A. METHODS: An isolated rabbit heart preparation perfused with the blood from a support rabbit was used. All hearts were divided into three groups according to the administration of U74500A (4 mg/kg, group A; n = 7), U74006F (4 mg/kg, group F; n = 7), or solvent (group S; n = 7) to the donor rabbit before preservation. After 24 hours of preservation with University of Wisconsin solution at 0 degrees C, all hearts were perfused with cross-circulated blood for 60 minutes with the Langendorff mode followed by 40 minutes in the working mode. RESULTS: After 10 minutes of reperfusion the serum lipid peroxide levels were significantly (p < 0.05) lower in group A (0.62+/-0.31 nmol/mL) than those in group S (2.1+/-1.3 nmol/mL) and group F (1.0+/-0.6 nmol/mL). The aortic flow rate at 10 mm Hg of left atrial pressure was significantly higher in group A (164+/-37 mL/min) than that of other groups (71+/-28 mL/min in group S and 97+/-28 mL/min in group F). There were no significant differences in high-energy phosphate levels after reperfusion among the three groups. CONCLUSION: These data imply that U74500A inhibits lipid peroxidation and prevents ischemia-reperfusion injury more efficiently than U74006F.

Animals↗
PubMed1998

A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumors.

BACKGROUND & AIMS: The c-kit gene encodes a receptor tyrosine kinase (KIT). Recently, we found gain-of-function mutations of the c-kit gene in gastrointestinal stromal tumors (GISTs). All mutations were confined within the 11 amino acids (Lys-550 to Val-560) in the juxtamembrane domain, but one GIST showed a novel deletion-type mutation at codon 579 (Asp) in the juxtamembrane domain. The aim of this study was to clarify whether the mutation is activating. METHODS: Mutant c-kit cDNA was transfected into an interleukin 3 (IL-3)-dependent Ba/F3 murine lymphoid cell line, and the magnitude of autophosphorylation of the mutant KIT was examined with or without stem cell factor (SCF), a ligand of KIT. An in vitro kinase assay was also performed. The biological behavior of the transfectant was estimated by both an in vitro proliferation assay and in vivo transplantation to nude mice. RESULTS: The mutant KIT exhibited constitutive phosphorylation and strong kinase activity without SCF. The transfectant grew autonomously without IL-3 and SCF, and it formed tumors in nude mice. CONCLUSIONS: Deletion at codon 579 (Asp) in the juxtamembrane domain of the c-kit gene is a novel gain-of-function mutation other than the region between Lys-550 and Val-560.

Amino Acid Sequence↗
PubMed1998

Endothelin A-receptor blockade worsens endotoxin-induced hepatic microcirculatory changes and necrosis.

BACKGROUND & AIMS: Endothelin 1 is considered to be an important regulator of sinusoidal blood flow and increases during endotoxemia. The purpose of this study was to investigate the role of endothelin 1 in hepatic microcirculation, oxygen transport, and liver injury during endotoxemia. METHODS: Male Sprague-Dawley rats were continuously infused with 2.5 mL/h of saline, 0.8 mg . kg-1 . h-1 of lipopolysaccharide (LPS), 3 mg . kg-1 . h-1 of BQ-485, an endothelin A-receptor antagonist, or LPS plus BQ-485 for 7 hours. RESULTS: BQ-485 infusion had no significant effect on hepatic microcirculation and liver injury. LPS increased the plasma levels of aspartate aminotransferase (AST) and total bilirubin and decreased the hepatic adenosine triphosphate (ATP) level and bile flow rate. LPS + BQ-485 infusion further increased the plasma levels of AST and total bilirubin and decreased the bile flow rate and the hepatic ATP level. Dual-spot microspectroscopy revealed mild decreases in sinusoidal erythrocyte velocity and oxygen transport in the LPS group and profound decreases in these parameters in the LPS + BQ-485 group. Histological examinations revealed massive necrotic changes in the pericentral regions of the LPS + BQ-485 group. CONCLUSIONS: These results suggest that blockade of endothelin A receptors disturbs hepatic microcirculation and oxygen transport and aggravates the necrotic injury induced by endotoxin.

Adenosine Triphosphate↗
PubMed1998

The pattern of alteration in flow velocity in the recanalized artery is related to left ventricular recovery in patients with acute infarction and successful direct balloon angioplasty.

OBJECTIVES: We evaluated the relationship between alterations in coronary flow velocity during the acute phase of acute myocardial infarction (AMI) and the recovery of left ventricular wall motion in patients who underwent successful primary angioplasty. BACKGROUND: The status of the coronary microcirculation is the major determinant of the prognosis of patients who have had successful reperfusion after AMI. Animal studies have shown that dynamic changes in regional flow are associated with the extent of infarction. Evaluation of alterations in coronary flow velocity in infarcted arteries may provide information about microcirculatory damage. METHODS: Flow velocity of the distal anterior descending artery was continuously monitored with the use of a Doppler guide wire immediately after recanalization for 18 +/- 4 h in 19 patients who underwent successful primary angioplasty after anterior AMI. Subjects were divided into two groups on the basis of the time course of alterations in average peak velocity (APV). Group D consisted of patients who had progressive decreases in APV through the next day (n = 9), and Group I comprised patients with an increase in APV after a transient decline (n = 10). Ejection fraction (EF) and regional wall motion (RWM) were assessed by left ventriculography performed on admission and at discharge. RESULTS: The APV at the end of monitoring was greater in group I than in group D. In group I, EF and RWM were significantly improved at discharge. The change in EF was greater in group I than in group D (17 +/- 9% vs. 4 +/- 9%, p = 0.007), as was the change in RWM (0.96 +/- 0.23 vs. 0.13 +/- 0.36 SD/chord, p < 0.0001). CONCLUSIONS: The alteration in flow velocity in recanalized infarcted arteries is related to left ventricular recovery. A progressive decrease in velocity after angioplasty implies no reflow, which is associated with a poor recovery of left ventricular function. Reperfusion injury may account in part for this phenomenon.

Aged↗
PubMed1998

Antisense sequences of the nbl gene induce apoptosis in the human promyelocytic leukemia cell line HL-60.

Apoptosis is induced by the transcriptional inhibitor actinomycin D (Act D) in various cell types, particularly many leukemic cell lines such as HL-60. A common feature of these cell lines is their high constitutive expression level of the nbl gene, which was originally isolated by virtue of its abundance in a Namalwa Burkitt lymphoma cDNA library. In contrast, cell lines which constitutively express nbl at low levels appear not to undergo typical apoptotic death in response to Act D. Apoptotic induction by Act D in cells which normally express nbl at high levels was found in this study to be closely associated with a decline in nbl mRNA levels, raising the possibility that apoptosis could be induced by lowering nbl expression levels in such cells. Transient expression of nbl antisense sequences in HL-60 cells decreased cell viability, and induced typical apoptotic morphology such as cell shrinkage, chromatin condensation and nuclear fragmentation. Incubation with nbl antisense oligomers also induced similar features in HL-60 cells and in another high nb-expressing cell line, Jurkat, but had little effect in HepG2 cells which constitutively express nbl at low levels. These findings suggest that lowering constitutively high levels of nbl expression can induce apoptosis.

Antineoplastic Agents, Hormonal↗
PubMed1998

Proliferative response of CD8+ gamma delta+ T cells to Streptococcus sanguis in patients with Behçet's disease.

To analyze the pathogenesis of Behçet's disease (BD), we investigated the immune response of peripheral blood T cell subsets from patients with BD to Streptococcus sanguis (S. sanguis) strain KTH-I, a bacteria suggested to be associated with the etiology of BD. Cultured peripheral blood mononuclear cells (PBMC) of patients with BD activated by lyophilized whole bacterium of S. sanguis were assayed by two-color flow cytometry using monoclonal antibodies (mAbs) specific for gamma delta+ T cell receptor, CD4 or CD8 molecules. The lymphostimulatory activity of S. sanguis to either gamma delta+ CD4-CD8-, gamma delta+ CD4-CD8+, gamma delta-CD4+CD8-, or gamma delta-CD4-CD8+ T cells was evaluated. The absolute number of gamma delta+ T cells from patients with BD (n = 8) as well as from healthy controls (n = 7) significantly increased after stimulation with S. sanguis, whereas gamma delta- T cells from both groups showed no response to S. sanguis. The absolute number of gamma delta+ CD8+ T cells from patients with BD significantly increased after stimulation with S. sanguis compared with healthy controls (p < 0.05). Peripheral gamma delta+ CD8+ T cells from patients with BD showed a significantly higher proliferative response to S. sanguis compared with healthy controls.

Adult↗
PubMed1998

Inhibition of endogenous expression of connective tissue growth factor by its antisense oligonucleotide and antisense RNA suppresses proliferation and migration of vascular endothelial cells.

Previously, we cloned an mRNA predominantly expressed in hypertrophic chondrocytes by differential display-PCR from a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8) that is identical to that of connective tissue growth factor (CTGF). In the present study, we investigated the roles of CTGF in the proliferation and migration of vascular endothelial cells using its antisense oligonucleotide and antisense RNA, because angiogenesis into the hypertrophic zone of cartilage occurs at the final step of endochondral ossification. Immunohistochemical and immunofluorescence techniques revealed that not only hypertrophic chondrocytes but also endothelial cells in the cost-chondral junctions of mouse ribs were stained with an anti-CTGF antibody in vivo. Northern blot analysis revealed that CTGF was strongly expressed in chondrocytic cells as well as bovine aorta endothelial (BAE) cells in culture, but not in other types of cells such as osteoblastic cells. Its expression in BAE cells was greater in the growing phase than in the confluent phase. When one-half of a monolayer of a confluent culture of BAE cells had been peeled off, only the cells proliferating and extending into the vacant area were stained with the anti-CTGF antibody. The addition of an antisense oligonucleotide inhibited the proliferation and extension of the BAE cells into the vacant area. The antisense oligonucleotide also inhibited the proliferation of BAE cells in the rapidly proliferating phase. In a Boyden chamber assay, pretreatment with the antisense oligonucleotide markedly inhibited the migration of BAE cells. Furthermore, the abilities to proliferate and migrate of BAE cells, which were stably transfected with expression vectors that generate the antisense RNA of CTGF cDNA, were markedly lower than those of the control. These findings suggest that endogenous CTGF expression is involved in the proliferation and migration of BAE cells.

Animals↗
PubMed1998

Expression of the SART-1 antigens in uterine cancers.

We recently reported that the SART-1 gene, encoding the SART-1(259) tumor antigen which is recognized by HLA-A26-restricted cytotoxic T lymphocytes (CTLs), is expressed in the cytosol of squamous cell carcinomas and adenocarcinomas. The present study deals with the expression of SART-1(259) and SART-1(800) antigens in uterine cancers. The SART-1(259) antigen was detected in the cytosol fraction of 4 of 8 uterine cancer cell lines, 24 of 74 (32%) uterine cancer tissues, 0 of 7 uterine myomas, and 0 of 5 non-tumorous uterine tissues. The SART-1(800) antigen was expressed in the nuclear fraction of all the uterine cancer cell lines, 41 of 74 (55%) uterine cancer tissues, 0 of 7 myomas, and 3 of 5 non-tumorous uterine tissues. The SART-1(259)+ uterine cancer cells were recognized by HLA-A24 restricted and SART-1 specific CTLs. Therefore, SART-1(259) antigen could be an appropriate vaccine candidate for a relatively large number of uterine cancer patients.

Adenocarcinoma↗
PubMed1998

Anthropometric and other risk factors for ovarian cancer in a case-control study.

Because it has been suggested that an environmental factor may play a role in the etiology of ovarian cancer, a case-control study was conducted to assess some environmental and other risk factors for ovarian cancer from 1994 to 1996 in northern Kyushu, Japan. We analyzed the data of 89 cases with epithelial ovarian cancer and 323 controls without any cancer or ovarian disorder. After controlling for the effect of potential confounders, the odds ratios of ovarian cancer across increasing quartiles of the heaviest body weight were 1.00, 1.15, 1.71, 2.29 (P = 0.008, test for trend). Significantly increased risks were noted for a history of diabetes mellitus (P < 0.05), and for a family history of ovarian cancer (P < 0.05). Significantly decreased trends for risk were obtained for the number of pregnancies (P < 0.01) and the number of live births (P < 0.001). This study provides additional support for an association between obesity and the risk of ovarian cancer. This relationship may at least partly explain the recent increase in the incidence of ovarian cancer in Japan, although possible contributions of other factors can not be ruled out.

Adult↗
PubMed1998

Effects of a gonadotropin-releasing hormone agonist on rat ovarian adenocarcinoma cell lines in vitro and in vivo.

To evaluate the biologic effects of the gonadotropin-releasing hormone (GnRH) agonist buserelin on rat ovarian adenocarcinoma cells in vivo and in vitro, female Wistar rats with primary ovarian adenocarcinoma induced by 7, 12-dimethylbenz(a)anthracene (DMBA) and the DMBA-OC-1 cell line established from a DMBA-induced rat tumor were used in this study. In vivo, daily administration of buserelin significantly suppressed the release of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone as compared with controls. Buserelin did not inhibit the growth of DMBA-induced tumors. However, histopathologically, there was increased central necrosis and a decrease in the number of neoplastic cells, with proliferation of connective tissue, in the group treated with buserelin. In vitro, FSH-induced proliferation of DMBA-OC-1 cells was suppressed by buserelin. Thus, this basic experimental study supports the potential use of a GnRH agonist to suppress the growth of ovarian cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Production and immunohistochemical characterization of monoclonal antibodies against ovarian antigen of the common tree shrew (Tupaia glis).

To study the ovarian function of the common tree shrew (Tupaia glis), monoclonal antibodies (MAb) against its ovarian antigen were produced. Several positive hybridomas were cloned and MAb-T2C9 (IgG) was examined for reactivity. Strong immunoreactivity of MAb-T2C9 was localized within the cytoplasm of luteal cells and in the theca interna cells of Graafian follicles. MAb-T2C9 reacted also with testicular interstitial cells and adrenocortical cells, except those of the zona glomerulosa. Similar reactions were seen in the goat and sheep. Western blotting analysis of the ovine corpus luteum after reaction with MAb-T2C9 revealed a single positive band of approximately 60 kDa. These findings suggest that MAb-T2C9 recognized protein molecules related to steroid synthesis.

Adrenal Cortex↗
PubMed1998

Histochemistry of complex carbohydrate in the major salivary glands of hoary bamboo rats (Rhizomys purinosus).

The major salivary glands (parotid glands, monostomatic sublingual glands and submandibular glands) were obtained from hoary bamboo rats (Rhizomys purinosus) and fixed in Bouin's solution. Paraffin sections were subjected to a battery of staining methods including lectin staining for demonstration of complex carbohydrates. Among the three major salivary glands, unique histochemical features were observed in the submandibular gland. Different from most myomorpha species, submandibular glands of the hoary bamboo rats have two types of secretory cells in the secretory endpieces. One type of cells showed positive reactions with Alcian blue (AB)(pH2.5), periodic acid-Schiff (PAS) and some lectins (peanuts agglutinin, Griffonia simplicifolia I, Maclura pomifera agglutinin). The granular ducts, which exist in animals belonging to suborder myomorpha, were not observed in the submandibular glands of this animal.

Animals↗
PubMed1998

Ovarian endometrioid adenocarcinoma coexistent with benign and borderline endometrioid adenofibroma: a case report.

A well-differentiated endometrioid adenocarcinoma coexistent with benign and borderline-malignant endometrioid adenofibroma was found in the ovary of a 64-year-old woman. She had vaginal bleeding caused by simple hyperplasia of the endometrium due to high levels of sex steroid hormones. A FIGO stage Ia solid ovarian tumor was identified. It was composed of irregularly shaped endometriotic glands with benign and borderline malignant cytologic features embedded in abundant fibromatous stroma. Well-differentiated malignant epithelium was adjacent to these areas, but fibromatous stroma was not predominant. She was treated by surgery and three cycles of chemotherapy. This paper describes this unusual tumor and reviews the literature.

Adenofibroma↗