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Biomedical subjects

Yasuhiko Ohta

Publications and source records attributed to Yasuhiko Ohta.

At least 37 records · Page 2Linked to original sources

The combination assay with circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9, and VEGF for diagnosing lymph node metastasis in patients with non-small cell lung cancer.

BACKGROUND: The aim of the present study was to evaluate the diagnostic utility of levels of circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9 (MMP-9), and VEGF and to verify that the combination assay of these circulating factors is a clinically useful indicator to predict the presence of lymph node metastasis in non-small cell lung cancer (NSCLC). METHODS: A series of 78 patients who underwent surgery for NSCLC was used in this study. Serum VEGF-C and VEGF and plasma MMP-9 levels were analyzed with enzyme-linked immunosorbent assay (ELISA) kits. Logistic regression models were used to analyze the influence of VEGF-C, MMP, and VEGF levels on the probability of presence or absence of lymph node metastasis. RESULTS: Patients with lymph node metastasis had higher serum VEGF- C, VEGF, and plasma MMP-9 concentrations than did those without metastasis (VEGF-C, P = .0004; VEGF, P = .001). Serum VEGF- C reached a sensitivity of 85% and specificity of 68% when a cutoff value of 1762.0 pg/mL was applied, while VEGF reached 80% sensitivity and 59% specificity at 316.8 pg/mL. MMP-9 reached a sensitivity of 63% and specificity of 75% when a cutoff value of 51.4 ng/mL was applied. In the ROC curve analysis, VEGF-C (0.761) had the biggest areas under the ROC curve, followed by MMP-9 (0.723) and VEGF (0.694). Combination assay of three markers had higher sensitivity and specificity for prediction than single-marker assays (AUC = 0.837). CONCLUSIONS: This study has confirmed that combination assay of three markers to determine VEGF-C, MMP-9, and VEGF expression in circulation detects lymph node metastasis in NSCLC with higher accuracy than single-marker assays.

Adult↗

Evaluation of estrogenic activity in diets for experimental animals using in vitro assay.

We used a modified yeast-based human estrogen receptor alpha (ER alpha) bioassay to determine the estrogenic activity in 22 kinds of diets for experimental animals. The estrogenic activity of each diet was reevaluated by comparison with a calibration curve of 17 beta-estradiol. Almost all of the diets had estrogenic activity. The diets for rabbits and guinea pigs had the highest estrogenic activity compared to any other diets, including those for rats and mice. Estrogenic activity was found in dried skim milk, fishmeal, soybean meal, and alfalfa meal. In the NIH-07 diet opened for the ingredients, estrogenic activity was nearly all derived from the alfalfa meal. Multiple assays were performed to evaluate potential seasonal variations in the estrogenic potency in the raw materials of the rat and mouse diets. We found that the estrogenic activity in these raw materials changed throughout the year.

Animal Feed↗

Metastasis of thyroid cancer to primary lung cancer.

We present a case of a 65-year-old woman whose thyroid cancer metastasized to the lesion of primary lung cancer. Ten years after total thyroidectomy for thyroid cancer, chest radiograph by medical check-up demonstrated three nodular lesions in the bilateral lung fields. Segmental resection of the left S6, partial resection of right S4 and left S10 were performed to remove those lesions. Histologically, small nodules in the right S4 and S10 were diagnosed as a metastatic tumor of thyroid and well differentiated adenocarcinoma, respectively. Left S6 lesion 1.5 cm in diameter was also diagnosed as well-differentiated adenocarcinoma (Noguchi type C), however, small metastatic foci of papillary adenocarcinoma was identified within the lesion which revealed to be "cancer in cancer metastasis". Metastasis of cancer to another primary cancer is a rare event. We discuss interesting phenomenon of cancer in cancer metastasis with a review of the literature.

Adenocarcinoma↗

Involvement of growth factors in induction of persistent proliferation of vaginal epithelium of mice exposed neonatally to diethylstilbestrol.

Neonatal treatment of female mice with natural and synthetic estrogens including diethylstilbestrol (DES) results in persistent proliferation and cornification of vaginal epithelium. In order to study the mechanism of persistent proliferation of vaginal epithelium, histological and biochemical changes were examined in the vagina of C57BL female mice exposed neonatally to 3 microg DES for 5 days. In intact control adult mice, ovariectomy induced apoptotic cell death in vaginal epithelial cells detected by in situ 3'-DNA nick end labeling method accompanied by low DNA synthesis detected by incorporation of bromodeoxyuridine. In neonatally DES-exposed adult mice, however, ovariectomy did not induce reduction of DNA synthesis and showed only a slight increase in apoptotic cells of vaginal epithelium. In neonatally DES-exposed mouse vagina, semi-quantitative reverse transcription polymerase chain reaction revealed a continuous higher expression of mRNAs encoding epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). These results indicate that neonatal DES exposure causes the increase in expression of EGF and TGF-alpha mRNA, possibly resulting in the induction of persistent proliferation and cornification of vaginal epithelium in mice.

Animals↗

Surgical resection of recurrent bilateral mediastinal liposarcoma through the clamshell approach.

Primary mediastinal liposarcoma is an unusual variant of mediastinal neoplasms. We describe a long-term survivor who underwent repeated operations. After resections through a posterolateral thoracotomy and median sternotomy, a third operation was performed for recurrent bilateral huge tumors through a clamshell incision, and both tumors were removed en bloc. Results of pathologic examination showed that both tumors were well-differentiated liposarcoma. The patient is currently well 16 years after the first operation. Aggressive surgical intervention whenever possible appears to improve the quality of life and prolong the survival of patients with mediastinal liposarcoma.

Female↗

Leiomyoma of an accessory tracheal bronchus.

We present a rare case of leiomyoma arising in an accessory right bronchus in a 55-year-old man who had been treated for bronchial asthma. Diagnosis was established on the results of bronchoscopic biopsy. An emergency operation was performed because the patient had begun to complain of severe dyspnea. The tumor was completely removed by electrocautery with a wire snare by rigid bronchoscopy. Postoperative bronchoscopic findings revealed a tracheal bronchus arising above the carina, and the root of the tumor existed in the orifice of the branch. Final histology revealed a leiomyoma.

Bronchi↗

Chest CT and serum vascular endothelial growth factor-C level to diagnose lymph node metastasis in patients with primary non-small cell lung cancer.

STUDY OBJECTIVE: Accurate tumor staging is essential for choosing the appropriate treatment strategy for lung cancer. CT of the chest is the most commonly used noninvasive staging method of the lymph node metastasis, but it is far from satisfying. We evaluated whether circulating vascular endothelial growth factor (VEGF)-C could give additional information for diagnosing lymph node metastasis in patients with lung cancer. PATIENTS AND METHOD: Serum samples were obtained from 116 patients with primary non-small cell lung cancer (NSCLC). All patients underwent preoperative CT of the thorax. Clinical T and N stages were compared to the final T and N stages obtained from pathologic findings. Serum VEGF-C concentration was assayed by commercially available sandwich enzyme-linked immunosorbent assay. We evaluated the utility of serum VEGF-C level as a marker for nodal metastasis comparing the utility of CT. RESULTS: Preoperative and final T categories completely agreed in 82.8%. Regarding nodal metastasis, the accuracy of CT was 68.1%. Patients with lymph node metastasis showed higher serum VEGF-C concentrations than those without lymph node metastasis (p = 0.0007). Serum VEGF-C reached the highest sensitivity and specificity in diagnosing lymph node metastasis when a cut-off value of 1,850.6 pg/mL was applied (sensitivity, 70.0%; specificity, 77.3%). Serum VEGF-C visually correlated with CT scan in the detection of lymph node metastasis (sensitivity, 74.0%; specificity, 80.3%; positive predictive value, 74.0%; negative predictive value, 80.3%; accuracy, 77.6%). When the cases were limited to adenocarcinoma, better results could be obtained. CONCLUSIONS: Serum VEGF-C is a reliable marker for lymph node metastasis in NSCLC. Serum VEGF-C evaluation and CT examination are complementary to each other for accurate lymph node staging in NSCLC.

Adenocarcinoma↗

Epithelial c-jun and c-fos are temporally and spatially regulated by estradiol during neonatal rat oviduct differentiation.

Expression of transcription factors binding to the activating protein-1 (AP-1) site is induced by estrogens in association with epithelial proliferation in the uterus, but, in the oviduct, the relationship between cell proliferation and differentiation and AP-1 transcription factors is not well understood. In the developing rat oviduct, we found that proliferation and differentiation of epithelial cells were region-dependently regulated by 17beta-estradiol (E2). To determine the role of AP-1 transcription factors in the development of rat oviduct, we performed immunohistochemistry for epithelial c-jun and c-fos proteins in E2-untreated and -treated newborn rats. E2 increased the expression of c-jun and c-fos during proliferation of undifferentiated epithelial cells, but diminished both proteins during accelerated differentiation of ciliated epithelial cells. A pure estrogen receptor (ER) antagonist, ICI 182,780, inhibited changes in their expression during both cell proliferation and differentiation. Importantly, no reduction of c-jun was noted in the epithelial cells of the foxj1-deficient oviduct, which lacks cilia development. This study shows that c-jun and c-fos are regulated during epithelial cell proliferation and differentiation in a region-specific manner. This provides critical information for understanding the molecular and cellular mechanisms of the development of the neonatal oviduct.

Animals↗

Serum vascular endothelial growth factor-C level in patients with primary nonsmall cell lung carcinoma: a possible diagnostic tool for lymph node metastasis.

BACKGROUND: The authors measured circulating vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor (VEGF) levels in patients with primary nonsmall cell lung carcinoma and assessed its usefulness as a diagnostic tool for determining lymph node metastasis. METHODS: Ninety-two patients with nonsmall cell lung carcinoma and 58 patients with benign tumors of the lung were included in the current study, as well as 42 healthy control patients. Circulating VEGF-C and VEGF levels were assessed by enzyme-linked immunosorbent assay. RESULTS: Serum VEGF-C concentration was higher in patients with lung carcinoma than in patients with benign tumors or in healthy control patients. Patients with lymph node metastasis revealed higher serum VEGF-C and VEGF concentrations than those without. The median level of VEGF-C and VEGF according to lymphatic vessel invasion and venous invasion was higher in the group with invasion than in the group without. These differences were most significant among patients with VEGF-C with lymphatic vessel invasion (P = 0.0066 vs. P = 0.026) and in patients with VEGF with venous invasion (P = 0.19 vs. P = 0.011). Serum VEGF-C levels reached a sensitivity of 79% and a specificity of 72% with a cutoff value of 1756.0 pg/mL, whereas VEGF levels reached 68% sensitivity and 70% specificity at 327.8 pg/mL. If 92 patients were divided into 4 groups according to the combination of VEGF-C and VEGF levels, the positive predictive value was 84.2%, the negative predictive value was 95.8%, and accuracy was 93.1%. CONCLUSIONS: Circulating VEGF-C levels may provide additional information for distinguishing between the absence and presence of lymph node metastasis in patients with lung carcinoma.

Adult↗

Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo.

The dendritic spine is an important site of neuronal plasticity and contains extremely high levels of cytoskeletal actin. However, the dynamics of the actin cytoskeleton during synaptic plasticity and its in vivo function remain unclear. Here we used an in vivo dentate gyrus LTP model to show that LTP induction is associated with actin cytoskeletal reorganization characterized by a long-lasting increase in F-actin content within dendritic spines. This increase in F-actin content is dependent on NMDA receptor activation and involves the inactivation of actin depolymerizing factor/cofilin. Inhibition of actin polymerization with latrunculin A impaired late phase of LTP without affecting the initial amplitude and early maintenance of LTP. These observations suggest that mechanisms regulating the spine actin cytoskeleton contribute to the persistence of LTP.

Actin Depolymerizing Factors↗

Thymic carcinoid tumor.

In this report on 3 cases of thymic carcinoid, tumors recurred in 2 patients not undergoing lymph node dissection. We review 47 cases of this disease taken from the Japanese literature, and discuss surgical procedures for reducing recurrence. In 9 of 20 cases of recurrence in encapsulated thymic carcinoid, lymph nodes were not dissected in eight. Differential diagnosis of an anterior mediastinal tumor should include thymic carcinoid, for which lymph nodes should be routinely dissected, even when the tumor is encapsulated.

Adult↗

The dinucleotide microsatellite polymorphism of the IFNAR1 gene promoter correlates with responsiveness of hepatitis C patients to interferon.

We studied a possible correlation between the dinucleotide microsatellite polymorphism of the interferon alpha/beta receptor-1 gene (IFNAR1) and responsiveness of hepatitis C patients to interferon therapy. The length of GT-repeat (n of (GT)(n)) in the IFNAR1 promoter was determined in 157 patients, of whom 50 were responders and 107 were nonresponders to interferon. The genotypes 5/5 (i.e. homozygotes of (GT)(5)) and 5/14 (i.e. heterozygotes of (GT)(5) and (GT)(14)) were more frequently found in responders than in nonresponders: 80 versus 58%, P=0.008. Thus, determining (GT)(n) of the IFNAR1 promoter may help predict treatment outcome in patients treated with interferon alpha and/or beta. In addition, we sought for genetic polymorphism in the promoter region of the interferon alpha/beta receptor-2 gene (IFNAR2), and found single nucleotide polymorphisms (SNPs) at -134 and -75. But these SNPs did not show a clinical significance, as compared with the GT-repeat in IFNAR1, in the context of interferon responsiveness.

Journal Article↗

Enforced expression of oxygen-regulated protein, ORP150, induces vacuolar degeneration in mouse myocardium.

Although the 150 kDa oxygen-regulated protein (ORP150) is known as a protein induced by low oxygen tension or ischemical insult, its possible role has not been fully investigated in vivo. To investigate the intracellular function of this protein, we generated the ORP150 over-expressing transgenic mice (ORP-Tg mice) under beta-actin promoter, and established three independent lines of the transgene expressed mice. All lines invariably showed growth retardation. Over-expression of ORP150 was confirmed by western blotting in heart, brain, spleen, skeletal muscle, pancreas, lung, thymus, and kidney. To ascertain the relationship between the over-expression of the ORP150 and the growth retardation in the transgenic mice, we examined pathological changes in the transgenics. In the ORP-Tg mice, vacuolar degeneration appeared in the heart. The degeneration in the myocytes became conspicuous with advancing age. Immunostaining demonstrated ORP150 in the vacuoles of degenerating myocytes. Electron microscopical findings revealed striking development of intracellular membrane system, for example, rough endoplasmic reticula (rER), vacuoles and Golgi bodies, swelling of sarcoplasmic reticulum, and lysis of myofibrils and mitochondria. These findings indicate that ORP150 may locate in the rER and other outer compartment of ER, and that constitutive over-expression of ORP150 in the heart induces vacuolar degeneration in myocytes, resulting in growth retardation of the transgenics.

Actins↗

Helicobacter pylori stimulates inducible nitric oxide synthase in diverse topographical patterns in various gastroduodenal disorders.

Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) acts cytotoxically and contributes to inflammation. We explored the roles of iNOS in the pathogenesis of Helicobacter pylori-associated diseases. Using reverse-transcribed PCR, we examined topographical patterns of iNOS mRNA expression in the gastroduodenal mucosa in H. pylori-negative controls and H. pylori-positive patients with duodenal ulcer (DU), gastric ulcer (GU), and ulcer-free gastritis. iNOS expression showed topographical variations among the tested disorders. As compared to controls, DU had a significantly higher expression of iNOS mRNA in the duodenum, GU in the antrum and duodenum, and gastritis in the antrum and corpus. H. pylori eradication yielded a significant reduction of iNOS mRNA in the duodenum of DU and in the antrum of GU. Diverse topographical patterns of H. pylori-induced iNOS expression may contribute to mechanisms by which H. pylori elicits different clinical disorders.

Amoxicillin↗

Thoracoscopic appearance of bilateral spontaneous pneumothorax.

STUDY OBJECTIVES: We investigated the macroscopic features of bilateral pneumothorax (BLP) and compared them with those of unilateral pneumothorax (ULP). METHODS: Surgical cases of spontaneous pneumothorax (236 cases) were divided into two groups based on unilateral occurrence (206 cases) or bilateral occurrence (30 cases). The patients were divided into three groups by the macroscopic findings of lung disease. The first group consisted of those patients with solitary and small bullae (type I pneumothorax), the second group consisted of those with multiple and large bullae (type II pneumothorax), and the third group consisted of those with an aggregation of diffuse and tiny bullae (type III pneumothorax). RESULTS: In metachronous BLP cases, 18 patients (66.7%) revealed type III pneumothorax in the first occurrence site, and 13 of 18 patients (72.2%) revealed type III pneumothorax in the contralateral site. Type III pneumothoraces were more frequently found in patients with BLP (18 of 27 patients; 66.7%) compared with ULP (73 of 206 patients; 35.4%; p = 0.0086 [chi(2) test]). During a follow-up ranging from 12 to 129 months (median, 69 months), 7 patients (23.3%) in the BLP group developed recurrences. This rate was higher than that of the ULP group (5.3%; p = 0.0009 [chi(2) test]). Contralateral CT scan findings of their first occurrence were retrospectively reviewed. In 3 patients (15.8%) in the BLP group and 17 patients (12.3%) in the ULP group, apical lung bullae and blebs (ruptured or intact) could be detected on the contralateral lung (p = 0.703 [chi(2) test]). CONCLUSIONS: The patients with an aggregation of diffuse and tiny bullae in their thoracoscopic findings had a high risk of contralateral recurrence. Macroscopic lung appearance in the contralateral site in such patients tended to reveal the same type as that in the primary site. CT scanning was not useful for predicting the risk of contralateral occurrence.

Adult↗

Peripherally located occult lung cancer with AMFR expression.

A 67-year-old man was referred to our hospital because of positive sputum cytology. Despite detailed examination, the malignant cell source remained elusive. Twenty months later, CT revealed two nodules in the right S1 and S10 regions which were resected. A year following the operation, gastoendoscopy showed a stomach tumor. Total gastrectomy with lymph node dissection was performed. Histologically, this patient was diagnosed with double primary lung cancer with metastasis to the stomach. The tumors of the lung, stomach and tumor cells in the sputum showed the same immunoreactivities of autocrine motility factor receptor (AMFR). In our institution, of 38 occult lung cancers encountered during the past 10 years, four (10.5%) occurred in the peripheral region. The presented four cases of radiologically occult lung cancer in the peripheral resion revealed bad prognosis, as three out of four patients were dead within 24 months after surgery. All of the four cases showed venous invasion, though the size of the primary tumor was small. Careful follow-up, including monitoring for distant metastasis, is necessary in radiologically occult peripheral lung cancer.

Aged↗