Biomedical subjects

Yasuhiko Ohta

Publications and source records attributed to Yasuhiko Ohta.

At least 19 recordsLinked to original sources

PubMed2006

Mirror glasses for minimally invasive surgery.

INTRODUCTION: The operator performing minimally invasive surgery is prevented from seeing the whole field with both eyes by the restricted small thoracotomy incision. To overcome this problem, we developed mirror glasses. METHODS: Use of these glasses was evaluated in terms of the time required for threading of sutures with endoscopic forceps. Three surgeon ligated thread a suture five times with and without use of the glasses in the box, and the mean time was calculated for each surgeon. RESULTS: The time required for ligation (mean +/- SD) was 24.2 +/- 2.9 s with mirror glasses and 27.0 +/- 2.5 s without the glasses (p = 0.01). CONCLUSION: The mirror glasses may be found useful for fine manipulation for minimally invasive surgery.

Equipment Design↗

PubMed2006

Ontogenic expression of estrogen receptor-alpha in female rat corneas.

PURPOSE: To investigate ontogenic expression of estrogen receptor (ER)-alpha in female rat corneas, as part of basic studies to elucidate the mechanism of estrogenic effects on the corneas. METHODS: The expression and localization of ERalpha were determined using quantitative reverse transcribed-polymerase chain reaction methodology and immunohistochemistry in the corneas of female rats on day 14 of gestation and postnatal days (PNDs) 0, 21, and 60. RESULTS: Quantitative analysis of ERalpha mRNA revealed that ERalpha gene expression increased approximately 4 times on PND 21 and about 10 times on PND 60, as compared with expression levels detected on PND 0. Immunohistochemical analysis revealed that expression of ERalpha protein was evident only in nuclei of the corneal epithelial cells from PND 21 onward. CONCLUSION: Ontogenic expression of ERalpha occurred in female rat corneas.

Animals↗

PubMed2006

Molecular cloning of estrogen receptor alpha (ERalpha; ESR1) of the Japanese giant salamander, Andrias japonicus.

Estrogens are essential for normal reproductive activity in females and males and for ovarian differentiation during a critical developmental stage in many vertebrates. To understand the molecular mechanisms of estrogen action and to evaluate estrogen receptor ligand interactions in the Japanese giant salamander (Andrias japonicus), we isolated cDNA encoding the estrogen receptor (ER) from the liver. A full-length Japanese giant salamander ER cDNA (jgsER) was obtained using 5' and 3' rapid amplification cDNA ends (RACE). The deduced amino acid sequence of the jgsER showed high identity to the Xenopus ERalpha (ESR1) (77.7%). We have applied both the conventional ERE-luciferase reporter assay system and the GAL4-transactivation system to characterize this receptor. In two different transient transfection assay systems using mammalian cells, the jgsER protein displayed estrogen-dependent activation of transcription. The GAL4-transactivation system showed about 10-fold greater activity of the estrogen receptor by hormone when compared to the conventional ERE-luciferase reporter assay system. Tissue distribution of ERalpha mRNA was examined and kidney, ovary and liver exhibited expression. This is the first isolation of an estrogen receptor from a salamander and also is the first functional cDNA obtained from the Japanese giant salamander, an endangered species considered a special natural monument of Japan.

Amino Acid Sequence↗

PubMed2006

Results of initial operations in non-small cell lung cancer patients with single-level N2 disease.

BACKGROUND: There is still debate regarding the use of surgery in the management of non-small cell lung cancer patients with N2 disease. The primary aim of the present study was analysis of the results of initial operations in non-small cell lung cancer patients with single-level N2 disease. METHODS: Ninety-four patients with the disease who underwent initial surgery consisting of complete resection of the primary site plus systematic lymphadenectomy were examined. We also immunohistochemically examined lymphatic vessel density and vascular endothelial growth factor-C expression. RESULTS: The overall 5- and 10-year survival rates for the 94 patients were 27.1% and 12.1%, respectively, with a median survival of 22 months. When stratified by skipping status, the 5-year survival rates for the patients in skip-N2 and non-skip-N2 groups were 33.4% and 19.8%, respectively (p = 0.0189). Skip metastasis, T factor, subcarinal lymph node metastasis, and adjuvant chemotherapy were recognized as independent prognostic indicators. In both skip-N2 and non-skip-N2 groups, distant relapse was the dominant pattern of recurrence. Although the peritumoral lymphatic vessel density was associated with vascular endothelial growth factor-C expression in tumors, the lymphangiogenic profile appeared to be different between skip-N2 and non-skip-N2 tumors, suggesting different nodal metastatic process. CONCLUSIONS: Lung cancer patients with single-level N2 disease are an oncologically heterogeneous cohort. Although further studies involving randomized comparisons are required, the poor outcomes found here indicate that the initial operation has yet to be validated for patients with this disease.

Adult↗

PubMed2006

Pathologic and biological assessment of lung tumors showing ground-glass opacity.

BACKGROUND: We evaluated the pathologic and biological aspects of lung tumors 3.0 cm or less in diameter with the appearance of ground-glass opacity (GGO). METHODS: Of 988 patients with non-small cell lung cancer who underwent operations at our institute between January 1994 and December 2004, 87 resected lung tumor specimens that showed GGO appearance on helical computed tomography were obtained from 81 patients. Forty-four lesions were pure GGO with no solid component in the tumor and 43 lesions were mixed GGO consisting of areas of attenuation with a solid component. Together with histological features, MIB1 and nm23 expression within tumors were examined immunohistochemically. RESULTS: The mean tumor size in the pure GGO group was significantly smaller than that in the mixed GGO group. The composition of pathologic subtypes and biological characteristics were clearly different between the two groups. Although atypical adenomatous hyperplasia and localized bronchioloalveolar cell carcinoma of Noguchi's A and B were the predominant pathologic subtypes and nm23 negativity was rare in the pure GGO group, a high score for expression of MIB1 was often found in pure GGO tumors even though the tumors were less than 10 mm in diameter. CONCLUSIONS: If the tumor is 2 cm or less in diameter, the ability of invasion and metastasis seems to be low in pure GGO tumors. However, the proliferation ability of these tumors suggests the necessity of a careful follow-up schedule if the tumor is greater than 5 mm in diameter. For mixed GGO tumors, surgical resection instead of observation is justified.

Carcinoma, Non-Small-Cell Lung↗

PubMed2006

Surgical results in T2N0M0 nonsmall cell lung cancer patients with large tumors 5 cm or greater in diameter: what regulates outcome?

BACKGROUND: We assessed the surgical results along with the clinical and biological features of nonsmall-cell lung cancer (NSCLC) patients with localized large tumors. METHODS: The study population consisted of 86 NSCLC patients who underwent complete resection of tumors 5 cm or larger in diameter in stage IB (T2N0M0). We immunohistochemically assessed the expression of angiostatin and endostatin. RESULTS: The median tumor size was 6.0 cm (range, 5 to 14 cm). The operative procedures used were lobectomy in 71 cases, bilobectomy in 8 cases, and pneumonectomy in 11 cases. Fifty patients (58.1%) relapsed during the mean follow-up period of 33.6 +/- 4.5 months. The median disease-free interval was 9 months. Of 44 recurrent patients whose disease-free interval could be identified, 25 patients (56.8%) relapsed within 12 months after the operation. The overall 5- and 10-year survival rates were 42.0% and 24.2%, respectively. Multivariate analysis showed that the degree of pleural involvement and angiostatin expression within the tumor were independent prognostic indicators. The endostatin expression within tumors also had a weaker relationship with outcome. CONCLUSIONS: Long-term surgical results were poor and early relapse was common in this cohort. In addition to pleural involvement, the tumor-induced expression of angiostatin and endostatin merit further investigation to gain possible insights into selection of patients who will benefit from surgery as the first line treatment.

Aged↗

PubMed2006

Global gene expression in mouse vaginae exposed to diethylstilbestrol at different ages.

Estrogens regulate proliferation and differentiation of cells in target organs such as the female reproductive tract. In mature mice, estrogens stimulate cell proliferation, whereas ovariectomy results in atrophy of the female reproductive tract. In contrast, perinatal exposure to estrogens, including diethylstilbestrol (DES), induces persistent, ovary-independent vaginal stratification and cervico-vaginal tumors later in life. These effects are due to altered cell fate following DES exposure during a critical developmental period. The detailed mechanisms underlying the reversible and irreversible cell proliferation in vaginae induced by DES at different ages has not been clarified. Therefore, we examined differences in gene expression pattern using DNA microarray analysis in mouse vaginae 6 hrs after a single injection of 2 mug DES per gram of body weight, and proliferation of vaginal epithelial and stromal cells 24 hrs after the injection at postnatal days (PNDs) 0, 5, 20, and 70. After DES stimulation, vaginal epithelial and stromal cells showed cell proliferation at PNDs 20 and 70, and at PNDs 0 and 5, respectively. DNA microarray analysis exhibited 54 DES-induced genes and 9 DES-repressed genes in vaginae at PND 0, whereas more than 200 DES-induced genes were found in vaginae at PNDs 5 and 20, and 350 genes at PND 70. Clustering analysis of DES-induced genes in the vaginae at different ages revealed that genes induced by DES at PND 5 were closer to the adult type than that of PND 0. Genes related to keratinocyte differentiation, such as Gadd45alpha, p21, 14-3-3 sigma, small proline-rich protein 2f (Sprr2f), and Krupple-like factor 4 (Klf4), were induced by DES. The number of DES-induced genes during the critical period, PND 0, was smaller than those found after the critical period. These results give insight toward understanding the molecular mechanisms underlying the critical period in mouse vaginae.

Animals↗

PubMed2006

In vitro sensitivity to platinum-derived drugs is associated with expression of thymidylate synthase and dihydropyrimidine dehydrogenase in human lung cancer.

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are critical enzymes in nucleic acid metabolism. Proliferating cell nuclear antigen (PCNA) is a specific protein that is correlated with proliferative activity of cells. The TS gene has a variable number of tandem repeats (VNTR) in its 5'-untranslated region and a single nucleotide polymorphism (SNP) in the VNTR area. We examined the association of in vitro sensitivity to anticancer drugs with TS polymorphism, TS, DPD, and PCNA mRNA expression using human lung cancer tissues. Seventy-eight surgically resected lung cancer tissues were tested for in vitro sensitivity to 5-fluorouracil, cisplatin (CDDP), carboplatin (CBDCA), irinotecan, docetaxel, and gemcitabine by histoculture and MTT assay. The TS polymorphisms were analyzed by PCR and PCR-RFLP. TS, DPD, and PCNA mRNA expression levels were quantified by real-time RT-PCR and normalized relative to beta-actin mRNA expression. The inhibition rates (IRs) of CDDP and CBDCA were significantly correlated with TS/PCNA, the ratio of TS/actin and PCNA/actin, and DPD/PCNA, the ratio of DPD/actin and PCNA/actin. This correlation was further explored by subgroup analyses according to TS VNTR or TS functional type, in which 2R/3G, 3C/3G, or 3G/3G were classified into H-type group and 2R/2R, 2R/3C, or 3C/3C into L-type group. The associations of TS/PCNA and DPD/PCNA with the IRs of CDDP, CBDCA remained significant in the 3R/3R group and H-type group. These results suggest that in vitro sensitivity to platinum-derived drugs, CDDP and CBDCA, is associated with PCNA-normalized mRNA expression of TS and DPD in human lung cancer tissues, as affected by the TS polymorphism. The clinical significance of these pharmacogenomic markers for chemotherapy regimens with platinum-derived drugs should be investigated further for personalized treatment of lung cancer.

Adult↗

PubMed2005

Effects of bisphenol A given neonatally on reproductive functions of male rats.

Male Sprague-Dawley rats (Crj:CD (IGS) were treated neonatally with bisphenol A (BPA) to evaluate effects on reproductive parameters. Animals were given BPA subcutaneously in corn oil to dosages of 0.002-97 mg/kg body weight, or 0.9 mg/kg 17beta-estradiol (E2) once a day from postnatal day (PND) 0 to PND 9. Preputial separation, copulatory rate, fertility rate, sperm analysis, serum testosterone levels, and gene expression in the testis were assessed. Males in the E2 group showed a decrease in testis weight and alterations of estrogen-mediated gene expression in the testis on PND 10, and by PND 150 incomplete preputial separation, decreases in the copulatory rate, testicular and accessory organ weights and number of sperm. In contrast, males in all BPA groups showed normal reproductive parameters. These results indicate that in male rats, BPA given during the neonatal period neither affected reproductive function nor evoked estrogen-mediated gene responses in the testis.

Animals↗

PubMed2005

Retrospective review of lung cancer patients with pleural dissemination after limited operations combined with parietal pleurectomy.

BACKGROUND AND OBJECTIVES: The long-term control of malignant effusion is necessary to achieve long-term survival in lung cancer patients with carcinomatous pleuritis. This report describes our results of limited operations including parietal pleurectomy (pl) on a hypothesis that the most effective target area for controlling malignant pleural effusion is the parietal pleura. METHODS: Forty-two patients with pleural dissemination with/without malignant pleural effusion were analyzed retrospectively. The operative procedures used were partial resection of the primary site with pl in 20 cases, segmentectomy with pl in 2 cases, lobectomy with pl in 19 cases, and pl only in 1 case. Postoperative adjuvant treatment was performed in 31 patients. RESULTS: Adenocarcinoma was the dominant histology, and the pathological stages were IIIB in 34 cases and IV (intrapulmonary metastasis) in 8 cases. The overall 3-, 5-, and 10-year survival rates were 30.1%, 17.2%, and 10.3%, respectively. When stratified by the TNM classification, the overall 3-, 5-, and 10-year survival rates were 56.3%, 32.1%, and 24.1%, respectively, in the T4N0M0 group and 21.1%, 7.0%, and 0%, respectively, in the T4N1-2M0 group (P = 0.0257). Among the 24 patients whose recurrent patterns could be identified, only 2 patients developed recurrent malignant effusion. CONCLUSIONS: With appropriate patient selection, the use of limited surgery combined with pl followed by intrapleural and systemic chemotherapy appears to be effective in management of the disease.

Adult↗

PubMed2005

Construction of an electrochemical DNA chip for simultaneous genotyping of single nucleotide polymorphisms.

An electrochemical DNA chip was constructed for simultaneous genotyping of single nucleotide polymorphisms (SNPs) using genomic DNA extracted from blood samples. This chip consisted of electrodes located on a single piece of substrate and allele-specific oligonucleotide probes on the electrodes. As a first application, the 4 SNPs (MxA[-88], MxA[-123], MBL[X/Y], and MBL[A/B]), which have association with the efficacy of interferon therapy for HCV patient, were genotyped on the new DNA chip. Following hybridization of PCR products containing the 4 types of fragments, washing, bisbenzimide H33258 (Hoechst 33258) reaction and electrochemical analyses, 59 blood samples were genotyped by the chip method simultaneously. All procedures were completed within 2 h and the results were 100% concordant with those by the direct sequence method. The electrochemical DNA chip is expected to be a practical tool for SNPs genotyping.

Bisbenzimidazole↗

PubMed2005

Extended resection of mediastinal undifferentiated carcinoma after chemosensitivity test-guided induction treatment: report of a case.

We performed extended resection of primary mediastinal undifferentiated carcinoma, together with the superior vena cava and the upper lobe of the right lung, after effective induction chemoradiation therapy based on the results of a chemosensitivity test. Pathological examination of the resected specimen revealed that almost all of the tumor cells had died. The patient received adjuvant chemotherapy and has remained free from disease progression for 27 months since his operation. Our experience supports the effectiveness of an aggressive approach, in the form of chemosensitivity test-guided induction therapy, to treat this high-grade malignant disease, despite the risk of cancer dissemination.

Carcinoma↗

PubMed2005

Free pericardial fat pads can act as sealant for preventing alveolar air leaks.

PURPOSE: This study was performed to investigate the safety and efficacy of a method using free pericardial fat pads as a sealant to prevent intraoperative and postoperative alveolar air leaks. DESCRIPTION: Animal experiments were performed. After pulmonary parenchymal defects were created in 4 dogs, the alveolar air leaks were sealed with free pericardial fat pads. Clinical application was applied in 23 patients who underwent pulmonary resection, air leaks with stream of bubbles, or worse, were sealed with free pericardial fat pads. EVALUATION: All dogs survived for 1 month without complications. At sacrifice, all treated lungs had expanded adequately and the implanted fats remained on the lung surface. Histologic examination showed that the excised edge of the lung was closed with granulation. The clinical outcome showed the mean duration of air leaks, chest drain, and postoperative hospitalization were 2.3 +/- 3.1 days, 4.3 +/- 3.2 days, and 11.1 +/- 3.7 days, respectively. Recurrent air leaks were not observed after removal of the chest tube. No adverse effects were observed after surgery. CONCLUSIONS: The use of free pericardial fat pads was able to successfully prevent alveolar air leaks.

Adipose Tissue↗

PubMed2005

Prognostic significance of dysadherin expression in patients with non-small cell lung cancer.

OBJECTIVE: The aim of this study was to evaluate the expression of dysadherin and E-cadherin and to investigate their clinical significance as prognostic factors in non-small cell lung cancer. METHODS: Non-small cell lung cancer specimens were obtained from 131 patients undergoing clinically indicated operations at the Department of General and Cardiothoracic Surgery, Kanazawa University Hospital, between 1995 and 1997. All patients had undergone curative resection of the primary tumor, including systematic lymph node dissection. The avidin-biotin-peroxidase complex method was used for immunostaining of dysadherin and E-cadherin. RESULTS: Among the 131 lung cancer specimens, 46 (35.1%) tumors were positively stained with dysadherin. Preserved membranous E-cadherin staining was present in 45.8% (60/131) of cases. In this analysis dysadherin expression was not correlated with E-cadherin expression (P = .1333), but a significant association was observed between dysadherin expression and survival time. The overall survival of patients with dysadherin-positive tumors was significantly worse than that of those with dysadherin-negative tumors (P = .0059). Patients with reduced E-cadherin immunopositivity survived significantly shorter than those with preserved E-cadherin immunopositivity (P = .0406). The overall survival of patients with positive dysadherin and reduced E-cadherin expression was significantly worse than that of patients with negative dysadherin and preserved E-cadherin expression (P = .0002). Multivariate analysis revealed the independent prognostic value of dysadherin positivity, reduced E-cadherin expression, and lymph node metastasis on overall survival. CONCLUSIONS: Dysadherin expression is an independent prognostic factor of survival in patients with non-small cell lung cancer, and combined immunohistochemical analysis of dysadherin and E-cadherin expression might provide further prognostic information.

Aged↗

PubMed2005

150-kD oxygen-regulated protein is an essential factor for insulin release.

OBJECTIVE: This study was designed to show the induction and function of 150-kD oxygen-regulated protein (ORP150) in insulin secretion in vitro. METHODS: A mouse beta-cell line, MIN6 cells, was cultured in medium containing potassium channel openers or various concentrations of glucose (2-25 mmol/L). ORP150 expression was studied by reporter assay, Western blot, or Northern blot analysis, concomitantly with insulin secretion. In addition, MIN6 cells infected with ORP150 recombinant adenovirus were adopted to show the function of ORP150 in insulin release. RESULTS: ORP150 expression in MIN6 cells was suppressed dose-dependently by the potassium channel opener diazoxide. Both low glucose (<2 mmol/L) and high glucose concentrations (25 mmol/L glucose) significantly induced more ORP150 expression compared with 10 mmol/L glucose. The treatment with diazoxide or infection of ORP150 antisense adenovirus suppressed ORP150 expression, and glucose-stimulated insulin secretion was effectively prevented. CONCLUSION: These findings show the involvement of ORP150 in insulin secretion in MIN6 cells.

Adenoviridae↗

PubMed2005

Fluorescence bronchoscopy for selection of surgical procedure in patients with early staged endobronchial carcinoma.

BACKGROUND: It is sometimes difficult to determine the extent of resection in patients with endobronchial carcinoma because preoperative white-light bronchoscopic (WLB) examination is not sensitive enough to examine the extent fully. Light-Induced Fluorescence Endoscopy (LIFE) is recognized as a useful modality for the diagnosis of early staged bronchial carcinoma, but there have been no reports of its significance in surgical treatment. We have studied the influence of LIFE upon the selection of surgical procedures or other treatments in patients with endobronchial carcinoma preoperatively. METHODS: Conventional WLB and LIFE were performed within 7 days of operation. Biopsy specimens were taken from the marginal regions of the areas that were suspicious for malignancy on LIFE examination and WLB. We decided the resection line before operation and kept the resected central margin 1 cm apart from the area revealed as suspicious by LIFE. RESULTS: From January 1999 to March 2003, 75 patients underwent LIFE. LIFE was performed to decide the surgical procedures for 12 patients (16.0%). Surgical therapy was performed in 8 (66.7%). LIFE findings dramatically changed the surgical procedures for 3 patients, lobectomy changed to sleeve lobectomy in 2 and laser therapy to segmentectomy in 1. LIFE revealed larger abnormal areas of bronchial cancer compared to WLB in 7 (58.3%). Conversely, WLB overestimated the extent of abnormal area in 1 (8.3%). WLB revealed the same cancer area as LIFE in 4. In all patients, the resected bronchial margins were cancer free intraoperatively and postoperatively. CONCLUSION: LIFE can be more sensitive than WLB and be more beneficial for judging the extent of neoplastic bronchial changes for some patients. LIFE may be a useful modality for the preoperative selection of surgical procedures, especially whether sleeve resection is needed or not, for some centrally located superficial endobronchial carcinoma.

Aged↗

PubMed2005

Sex steroid hormone receptors in the developing female reproductive tract of laboratory rodents.

Many chemicals released into the environment potentially disrupt the endocrine system in wildlife and humans. Some of these chemicals exhibit estrogenic activity by binding to the estrogen receptors. The developing organism is particularly sensitive to estrogenic chemicals during the critical period in which the induction of long-term changes and persistent molecular alterations in female reproductive tracts occur. Perinatal mouse and rat models can be utilized as indicators for determining the consequences of exposure to exogenous estrogenic agents, including possible xenoestrogens or environmental endocrine disruptors. Estrogen receptors (ER) and estrogen responsive genes, therefore, need to be identified in order to understand the molecular basis of estrogenic actions. Recent identifications of ER subtypes and isoforms make understanding target organ responses to these estrogenic chemicals even more difficult. Indeed, many reports suggest that these chemicals do affect the reproductive and developmental processes of female laboratory rodents that had been perinatally exposed, and that interactions between sex steroid hormone receptors occur. Much information concerning the expression of sex steroid receptors in rodents has been reported concerning the normal development of the Müllerian duct. Thus, accumulated information on the expression of ER subtypes and isoforms as well as that of progesterone and androgen receptors in laboratory rodents is herein reviewed, in addition to the presentation of our own data.

Animals↗

PubMed2005

A surgical case of lung cancer in a patient with the left superior and inferior pulmonary veins forming a common trunk.

The anatomical abnormalities of the pulmonary veins may have a serious impact on complications that may arise during pulmonary lobectomy. We present a surgical case of left lung cancer in a patient, who was a 69-year-old male, with the left superior and inferior pulmonary veins forming a common trunk outside the pericardium. In this present case, because of extensive adhesions, incomplete lobulation, and tumor infiltration of the main pulmonary artery, we could not identity the common trunk with certainty before excising the left upper lobe. Although this patient was fortunately discharged without complications, there was no choice but to perform pneumonectomy because of the interruption of the inferior pulmonary vein. Retrospectively, the preoperative CT films showed the anatomical anomalies involving the pulmonary veins. However, since the length of the common trunk outside the pericardium was short and the inferior pulmonary vein was thinner than usual and its venous distribution conformed to a normal structure, the anatomy appeared normal. In excising the pulmonary lobe, it is mandatory to ascertain the distribution of the vascular system prior to surgery.

Aged, 80 and over↗