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Biomedical subjects

Y Minamiya

Publications and source records attributed to Y Minamiya.

At least 19 recordsLinked to original sources

[Thymolipoma in association with myasthenia gravis; report of a case].

An 18-year-old man was admitted with easy fatigue and muscle weakness. A diagnosis of myasthenia gravis was made. Chest X-ray showed no mediastinal abnormality, however, chest computed tomography (CT) showed a soft tissue mass in the thymus. The patient underwent extended thymectomy and small tumor (2 x 2 x 2 cm) was resected. On histological examination the tumor proved to be a thymolipoma composed of mature adipose elements containing cords and nests of thymic tissue. Symptoms of myasthenia gravis were dramatically improved after the operation. This case is the 12th in the world literature in which a thymolipoma is associated with symptoms of myasthenia gravis.

Adolescent↗

[Surgical treatment for pulmonary metastases from colorectal cancer].

Blalock first reported pulmonary resection for metastatic colorectal cancer in 1944. Since then, surgical resection of pulmonary metastases has been generally accepted as a standard therapeutic procedure in properly selected cases. Recently, the criteria of eligibility have been progressively expanded according to the development of radiological diagnosis using helical computed tomography (CT), widespread of minimum invasive video-assisted thoracic surgery. In this review summarized the surgical treatment of pulmonary metastases from colorectal cancer based on the recent literatures. Major areas of controversy remain with respect to the following aspects: prognostic factors (i.e., number of metastases, size of tumor, disease free interval, preoperative serum carcinoembryonic antigen level), procedure of operation (i.e., role of video-assisted thoracic surgery, lymphonode dissection), indication of surgical treatment on metastases both lung and liver, role of repeat thoracotomy for recurrence. For all above-mentioned points it appeared reasonable to try to the cooperative multicentric clinical prospective study.

Colorectal Neoplasms↗

[A case of recurrent lung cancer successfully treated with vinorelbine and cisplatin].

A 56-year-old female underwent lobectomy with ND2a lymph node dissection for left lung cancer in April 1999. Histopathological examination demonstrated moderately differentiated adenocarcinoma (pT2N2M0, stage III A). She received one course of a combination of etoposide and cisplatin as adjuvant therapy, followed by oral intake of UFT. In November 1999, a left para-aortic lymph node recurrence was found. She received radiation therapy (total 60 Gy) to the mediastinum. In April 2000, new lung and left supraclavicular lymph node recurrences were found. She received three courses of vinorelbine 20 mg/m2 (days 1, 8) and cisplatin 80 mg/m2 (day 1) followed by radiation therapy (total 50.4 Gy) to the left supraclavicular lesion. After the chemotherapy, a complete response (CR) of all metastatic lesions was achieved. Adverse reactions were grade 1 alopecia, grade 2 nausea/vomiting, grade 3 neutropenia, hypochromia, and injection site reaction. The combination of vinorelbine and cisplatin is a useful regimen in non-small-cell lung cancer.

Adenocarcinoma↗

Red blood cells attenuate sinusoidal endothelial cell injury by scavenging xanthine oxidase-dependent hydrogen peroxide in hyperoxic perfused rat liver.

AIMS/BACKGROUND: Rat liver perfused with an oxygenated buffered solution alone results in degenerative changes even when the perfusion flow is accelerated to give a sufficient oxygen supply. On the other hand, perfusion media supplemented with red blood cells (RBCs) preserve the viability of the liver. The present study was conducted to clarify how RBCs protect the isolated perfused liver. METHODS: The liver was perfused with and without RBCs in a perfusate equilibrated with supra-physiological oxygen tension at regulated inflow pressures, and controlled hepatic oxygen consumption. We examined alanine aminotransferase and purine nucleoside phosphorylase activity in the perfusate as specific markers of liver cells injury. Hydrogen peroxide (H2O2) production and morphological changes were determined using cerium electron microscopy. Apoptosis was detected by measuring CPP 32 protease activity and using TdT-mediated dUTP-digoxigenin nick end-labeling. RESULTS: When the liver was perfused with RBC-free buffer, H2O2 production and consequent injury progressing to apoptosis were initiated in the sinusoidal endothelial cells (SECs). After SECs were injured, H2O2 appeared in the hepatocytes. H2O2 production and associated degenerative changes were attenuated both morphologically and enzymatically by the addition of RBCs, a specific xanthine oxidase (XOD) inhibitor and the H2O2 radical scavenger, catalase. CONCLUSIONS: In the liver perfused with RBC-free buffer, H2O2 production and consequent injury were initiated in SECs. RBCs attenuate liver injury by scavenging XOD-dependent H2O2.

Alanine Transaminase↗

Cisplatin induces fas expression in esophageal cancer cell lines and enhanced cytotoxicity in combination with LAK cells.

OBJECTIVE: To establish a new therapeutic approach for the treatment of esophageal cancer, we investigated an alternative mechanism of immunotherapy for sensitizing target cells to effector cells. METHODS: Six human esophageal cancer cell lines were used. The expression of Fas antigen on tumor cells was determined by flow cytometry. The cytotoxic effect of cis-dichlorodiammineplatinum (CDDP) and anti-Fas antibody was evaluated using an MTT assay. The cytotoxic activity of LAK cells was measured by a (51)Cr release assay. RESULTS: Five out of six esophageal cancer cell lines expressed Fas antigen at various levels (26.2-61.5%), and Fas expression increased after CDDP treatment. The antitumor effect of anti-Fas antibody on the esophageal cancer cell line and the antitumor effect of LAK cells activated by IL-2 were enhanced by pretreatment with CDDP. After concanamycin A treatment to specifically evaluate Fas-dependent cytotoxicity, LAK cells expressing Fas ligand killed only Fas-positive cells, but not Fas-negative cells. An anti-Fas neutralizing antibody inhibited this cytotoxicity. DNA fragmentation was shown in a cell line that was treated with CDDP and anti-Fas antibody, and also in the targeted esophageal cancer cell line cocultured with LAK cells. CONCLUSION: Our results suggest a potential clinical application of CDDP as a Fas inducer to make esophageal tumors susceptible to Fas antigen and LAK cytotoxicity.

Antineoplastic Agents↗

Postoperative lung volume calculated by chest computed tomography in patients with esophageal cancer.

It has been reported that, due to the severe surgical stress of thoracotomy, respiratory function after esophagectomy under thoracotomy worsened as late as a month after surgery. To investigate the mechanism of the reduction of the respiratory function, we utilized chest CT to analyze separately the changes in the lung volume of the thoracotomized side and the other side. Here, we reported the results of our comparative study of lung volume and respiratory function, which was performed by spirogram before esophagectomy and 6 months afterwards. We selected twenty-three patients who had undergone esophagectomy under right thoracotomy. Fourteen of the selectees received standard thoracotomy, while the other nine had the anterior serratus muscle and the latissimus dorsi muscle preserved. Total lung volume was found to have decreased from a preoperative value of 4077 +/- 674 ml (mean +/- SD) to a postoperative value of 3964 +/- 774 ml, and right-lung volume significantly decreased from 2229 +/- 397 to 2023 +/- 397 ml, while left-lung volume tended to increase. While right-lung volume in standard thoracotomy displayed a significant decrease from 2264 +/- 334 to 1949 +/- 424 ml, that in muscle-preserving thoracotomy showed almost no change. Spirogram revealed that vital capacity had decreased from 3574 +/- 601 to 2666 +/- 576 ml, and forced expiratory volume in the first second showed a significant decrease from 2680 +/- 500 to 2249 +/- 485 ml. Comparing the decreasing rate, the correlation coefficients between right-lung volume and %VC was 0.58. These results suggested that a change of lung volume in the thoracotomized side could play a role in the post-operative decrease of vital capacity and that muscle-preserving thoracotomy might induce less surgical stress than standard thoracotomy.

Adult↗

Bcl-2 is located predominantly in the inner membrane and crista of mitochondria in rat liver.

Bcl-2 is now recognized as a potent inhibitor of apoptotic cell death. It has been reported that Bcl-2 is located in the mitochondria, endoplasmic reticulum, and nuclear membrane in some cell lines, and it is not expressed in normal human and rat liver. An earlier study showed that Bcl-2 is an inner mitochondrial membrane protein. On the contrary, the following investigations using immunoelectron microscopy demonstrated that Bcl-2 resides predominantly in the mitochondrial outer membrane. In this study, using a cryo-sectioning immunogold labeling technique and immunoblotting, we carefully determined the subcellular localization of Bcl-2. Here we report that Bcl-2 is expressed in normal rat liver, and it is located predominantly in the inner membrane and crista rather than in the outer membrane of mitochondria.

Animals↗

Endothelial myosin light chain kinase regulates neutrophil migration across human umbilical vein endothelial cell monolayer.

Although extravasation of neutrophils is a critical step in acute inflammation, the role of the endothelial cytoskeleton in neutrophil transmigration has not been fully investigated. We used an in vitro model of neutrophil transmigration across a monolayer of HUVEC cultured on amniotic membrane. Human neutrophils were allowed to migrate across the HUVEC monolayer in response to a gradient leukotriene B4 and then the number of migrated neutrophils were counted microscopically. We also followed endothelial F-actin and myosin filament formation using rhodamine-phalloidin and anti-myosin Ab staining. Myosin light chain (MLC) phosphorylation in endothelial cells was determined by immunoprecipitation of 32P-labeled HUVEC with anti-myosin polyclonal Ab. Normally, neutrophil migration induced F-actin formation, myosin filament formation, and MLC phosphorylation in HUVEC. When HUVEC was pretreated with the myosin light chain kinase (MLCK) inhibitor, ML-9, neutrophil migration was diminished and F-actin formation, myosin filament formation, and MLC phosphorylation were inhibited. Pretreatments of HUVEC with the intracellular calcium ion chelator, bis-(O-aminophenoxyl)ethane-N, N, N', N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM), and the calmodulin antagonist, trifluoperazine, had similar effects. These results indicate that a calcium/ calmodulin-dependent MLCK in endothelial cells regulates neutrophil transendothelial migration.

Actins↗

Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.

Wilson's disease, an autosomal recessive disorder, is characterized by the excessive accumulation of copper in the liver. WND (ATP7B) gene, which encodes a putative copper transporting P-type ATPase, is defective in the patients. To investigate the in vivo function of WND protein as well as its intracellular localization, WND cDNA was introduced to the Long-Evans Cinnamon rat, known as a rodent model for Wilson's disease, by recombinant adenovirus-mediated gene delivery. An immunofluorescent study and a subcellular fractionation study revealed the transgene expression in liver and its localization to the Golgi apparatus. Moreover, since the synthesis of holoceruloplasmin is disturbed in the Long-Evans Cinnamon rat, the plasma level of holoceruloplasmin, oxidase-active and copper-bound form, was examined to evaluate the function of WND protein with respect to the copper transport. Consequently, the appearance of holoceruloplasmin in plasma was confirmed by Western blot analysis and plasma measurements for the oxidase activity and the copper content. These findings indicate that introduced WND protein may function in the copper transport coupled with the synthesis of ceruloplasmin and that the Golgi apparatus is the likely site for WND protein to manifest its function.

Adenosine Triphosphatases↗

Peripheral edema after esophagectomy.

Patients who have undergone major surgery such as esophagectomy may develop peripheral edema in the immediate postoperative period, the cause of which is not fully understood. The purpose of this study was therefore to determine the mechanism of this phenomenon. Finger edema was measured as a marker for peripheral edema before and after esophagectomy in eight patients. Plasma interleukin-6 (IL-6) was also measured by an enzyme-linked immunosorbent assay. Finger edema markedly increased in the immediate postoperative period and remained significantly elevated until after postoperative day (POD) 3 compared to the preoperative value (P < 0.05). Plasma IL-6 also markedly increased in the immediate postoperative period and remained significantly elevated on POD 2 compared to the preoperative value (P < 0.05). The degree of finger edema highly correlated with the level of plasma IL-6 (r = 0.71, P = 0.0001). These findings indicate that peripheral edema after esophagectomy might be caused by a proinflammatory cytokine response.

Body Weight↗

[An analysis of the mechanism of postoperative hyperbilirubinemia following resection of thoracic esophageal cancer in terms of hepatic venous oxygen saturation and excessive systemic reactions].

Hepatic venous oxygen saturation (ShvO2), parameters of systemic circulation and cytokine (Interleukin 6) (IL-6)) level were measured in 21 patients with thoracic esophageal cancer in order to analyze the mechanism of occurrence of postoperative hyperbilirubinemia (PHB). ShvO2 fell during operation, especially during intrathoracic procedures, and a significant correlation was noted between the total time during which ShvO2 was below 60% and the postoperative peak serum bilirubin level (peak-Bil) (r = 0.595, p = 0.0037). Patients with PHB (group H) had worse systemic circulation and a lower oxygen supply postoperatively than patients without PHB (group N). Body weight and water balance recovered earlier in group N. Postoperatively, numbers of peripheral lymphocytes and platelets changed lower in group H, while CRP and IL-6 changed higher in group H. Furthermore, a significant correlation was noted between the IL-6 level just after operation and peak-Bil (r = 0.669, p = 0.0006). These results suggests PHB results from intraoperative liver hypoxia and poor postoperative systemic circulation. Individual severeness of reactions to the operative stress, excessive or adequate, plays a role in the occurrence of PHB as well.

Aged↗

Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver.

BACKGROUND & AIMS: Evidence is accumulating that hypoxic liver injury involves not only necrosis but also apoptosis. Reactive oxygen species can cause apoptosis. This study examined the hypothesis that H2O2 induces apoptosis in hypoxic rat liver. METHODS: Blood-perfused rat livers were made hypoxic by reducing the perfusion flow. H2O2 was detected by both 2',7'-dichlorofluorescein fluoroimaging and cerium electron-microscopic methods. To evaluate the apoptosis, the liver was stained with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. To further investigate the involvement of H2O2 in hypoxia-induced liver cell apoptosis, small pieces of liver in the cultured media were exposed to 0.5 mmol/L of reagent H2O2 and stained with the TUNEL method. RESULTS: In the hypoxic liver, H2O2 was produced predominantly by hepatocytes, and the number of apoptotic nonparenchymal cells was significantly increased, particularly in the midzone. All the apoptotic cells were positively stained with monoclonal antibody against the hepatic sinusoidal endothelial cells (SECs). In incubated liver pieces, reagent H2O2 induced apoptosis selectively in SECs. CONCLUSIONS: Low-flow hypoxia induces H2O2 production in hepatocytes, and this H2O2 induces apoptosis selectively in SECs in the rat liver.

Animals↗

The requirement of intercellular adhesion molecule-1 for neutrophil respiratory burst in the pulmonary circulation of rats infused with endotoxin.

Recently, we demonstrated direct evidence of respiratory burst of the neutrophil in the pulmonary circulation of the endotoxin-infused rat (Am. J. Respir. Crit. Care Med. 1995;152:348-354). To determine the role of intercellular adhesion molecule-1 (ICAM-1) in this model, we neutralized ICAM-1 using antirat ICAM-1 monoclonal antibody (mAb) 1A29. We observed and measured the number of sticking leukocytes and the amount of hydrogen peroxide (H2O2) in the pulmonary circulation of the endotoxin-infused rat by means of a fluoro-imaging technique. The rats received 4.5 mg/kg/h of endotoxin for 2 h. Ten rats received 2 mg/kg of mAb 1A29 20 min before the intravenous infusion of endotoxin. Although the pretreatment with mAb 1A29 did not reduce the number of leukocytes sticking to the pulmonary capillaries, it almost completely inhibited the H2O2 production of leukocytes in the rat lung infused with endotoxin. We confirmed that the leukocytes that produced H2O2 were neutrophil by an electron microscopic cerium technique. We conclude that, although ICAM-1 is not necessary for neutrophil to stick to the capillary in the rat pulmonary circulation infused with endotoxin, ICAM-1 is required for neutrophil H2O2 production in this model.

Animals↗

Platelet-activating factor mediates intercellular adhesion molecule-1-dependent radical production in the nonhypoxic ischemia rat lung.

It has been reported that reperfusion is the most important factor in ischemia-reperfusion (I/R) injury. However, causes of I/R injury in the lung are controversial, because oxygen is always supplied if ventilation continues. Therefore, we hypothesized that nonhypoxic ischemia without reperfusion is sufficient for lung injury. To test our hypothesis, we measured both hydrogen peroxide (H2O2) production in the pulmonary circulation, by digital imaging fluorescent dichlorofluorescein, and microvascular permeability (MVP), by the Evans blue extravasation technique in the nonhypoxic ischemia rat lung. We made a nonhypoxic ischemia rat lung by clamping the left pulmonary artery. Both H2O2 production and MVP increased in the nonhypoxic ischemia rat lung. We also determined the effect of oxygen removal by clamping the bronchus in advance of pulmonary artery occlusion, intercellular adhesion molecule-1 (ICAM-1) neutralization with monoclonal antibody 1A29, and platelet-activating factor (PAF) receptor antagonist CV6209 on H2O2 production and MVP. These treatments inhibited both H2O2 production and MVP increase. At high-power viewing of the fluorescent dichlorofluorescein image, H2O2 was detected in the leukocytes within pulmonary capillaries. These data indicate that the nonhypoxic ischemia without reperfusion alone causes radical production and increases MVP. Furthermore, PAF and ICAM-1 contribute to these reactions.

Animals↗

Direct measurement of doxorubicin concentration in the intact, living single cancer cell during hyperthermia.

BACKGROUND: It is well known that the effect of doxorubicin on cancer cells is enhanced by hyperthermia. The mechanism of this phenomenon is not fully understood. METHODS: Two esophageal squamous cell carcinoma cell lines, TE-2 and TE-6, were used; these cell lines have different sensitivities for doxorubicin. The cells were exposed to 1 microgram/mL of doxorubicin for 30 minutes. With a confocal laser scanning microscope and a transparent warming plate, doxorubicin concentration was measured continuously in the intact, living single cancer cells, and the two-dimensional distribution of the drug during hyperthermia (43 degrees C) was analyzed. RESULTS: A doxorubicin sensitivity difference was confirmed between TE-2 and TE-6 cells by colonogenic assay (P < 0.05). Hyperthermia increased the sensitivity of both cell lines to the drug (P < 0.05) and eliminated the sensitivity difference. Doxorubicin accumulated in the nuclei in both cell lines 30 minutes after exposure to the drug in a time-dependent manner (P < 0.05). Without hyperthermia, the doxorubicin concentration in the nuclei of the TE-2 cells (4.8 +/- 0.3 micrograms/mL) was higher than in the nuclei of the TE-6 cells (2.3 +/- 0.5 micrograms/mL) (P < 0.05). With hyperthermia, there was no significant difference in doxorubicin concentration between the nuclei of the TE-2 cells (20.8 +/- 1.3 micrograms/mL) and the nuclei of the TE-6 cells (16.5 +/- 3.9 micrograms/mL). CONCLUSIONS: Hyperthermia increased the uptake of doxorubicin in the nuclei of cancer cells. Thus, the authors concluded that hyperthermia increases the cells' sensitivity to the drug.

Antibiotics, Antineoplastic↗

Mediastinal extraadrenal myelolipoma: report of a case.

We herein report a case of surgically resected mediastinal extraadrenal myelolipoma. Myelolipoma is an uncommon tumor composed of adipose tissue and normal hematopoietic elements, and is most often found in the adrenal glands. We could find only five such cases of mediastinal myelolipoma in the English literature.

Adipose Tissue↗

Analysis of results of surgery performed over a 20-year period on 500 patients with cancer of the thoracic esophagus.

This study was conducted to examine the long-term outcome of 500 patients who underwent surgery for cancer of the thoracic esophagus during the past 20 years. Favorable results were obtained with postoperative adjuvant radiation and chemotherapy and there were no surgical deaths in the last 5 years. The mortality rate decreased from 17% prior to 1980 to 5% between 1981 and 1993, this being most probably attributable to the decreased incidence of suture leakage. With respect to changes in surgical techniques, during the initial years we performed intrathoracic anastomosis, after which sternal manubrium resection with anterior mediastinal esophagogastrostomy was carried out. Subsequently, we invented a technique for performing esophagogastrostomy via the posterior mediastinum. The posterior mediastinum was selected as the most physiologic route, based on measurement of tissue oxygen tension. Using blood flow determinations obtained by laser-Doppler velocimetry, we concluded that the effectiveness of thicker gastric tubes was superior to that of thin tubes. Esophagogastrostomy was performed in a shallow field in the cervical region, with the anastomosis ultimately positioned in the superior mediastinum and covered with mediastinal pleura.

Anastomosis, Surgical↗