Biomedical subjects

Toshiaki Tanaka

Publications and source records attributed to Toshiaki Tanaka.

96 records · Page 6Linked to original sources

PubMed2002

[Propofol anesthesia for a patient with progressive muscular dystrophy].

We gave propofol anesthesia to a patient with limb-girdle type of progressive muscular dystrophy. A 42 year-old male was to have skin graft for third degree burn. His respiratory function test showed %VC of 73.6% and %FEV1.0 of 107.6%. Arterial blood gas data were within normal ranges. He was anesthetized with propofol, fentanyl, vecuronium and nitrous oxide. During position change, Wenckebach type of second degree AV block occurred. AV block returned to sinus rhythm easily by injection of ephedrine hydrochloride and atropine sulfate, and reduction of propofol infusion rate. There were no perioperative respiratory complications and no clinical manifestations of malignant hyperthermia. Propofol anesthesia is suitable for limb-girdle type of progressive muscular dystrophy, because of very little possibility of triggering malignant hyperthermia, rapid awaking, minimal residual effects of the respiratory system, and easiness in controlling anesthetic depth.

Adult↗

PubMed2002

Clinicopathologic study of neovascularization and VEGF expression in superficial esophageal carcinoma.

Among superficial esophageal carcinomas (SECs), mucosal carcinoma (m) and submucosal carcinoma (sm) markedly differ regarding the presence or absence of lymph node metastases and long-term survival. To clarify differences in the growth pattern of these two superficial carcinomas, we investigated neovascularization around the site of tumor growth and expression of vascular endothelial growth factor (VEGF) in tumor cells, in patients undergoing radical esophagectomy or endoscopic mucosal resection (EMR). Moreover, we investigated whether these factors were related to the prognosis in patients undergoing treatment of SEC. This study included 90 SEC patients undergoing radical esophagectomy (surgery group) and 35 patients undergoing EMR (EMR group). For immunohistochemical staining antibodies against factor VIII-related antigen and against VEGF were used. The microvessels around the tumor were counted to calculate the vascular index (VI). VI and VEGF expression in the tumor were compared in relation to clinicopathologic findings. In the surgery group, the VI and the percent of VEGF-positive cells were significantly higher in the case of sm carcinomas. Furthermore, tumors with a high VI showed a significantly worse prognosis. In the EMR group, the VI and percent of VEGF-positive cells increased with the depth of the tumor. The VI and VEGF expression were significantly higher in sm carcinomas. This may in part explain the difference in cancer progression between m and sm carcinomas. In patients undergoing resection or EMR, examination of neovascularization using VI may be potentially useful in evaluating the prognosis of SEC.

Biomarkers, Tumor↗

PubMed2002

Intraarterial cellular immunotherapy for patients with inoperable liver metastases of esophageal cancer.

PURPOSE: We report 2 patients with refractory liver metastatic tumor after esophagectomy for advanced esophageal cancer, who responded markedly to locoregional cellular immunotherapy by repeated intraarterial infusions of autologous tumor cell-activated T lymphocytes (AuTL), even after they failed the standard chemotherapy of cisplatin (CDDP) and 5-fluorouracil (5-FU). METHODS: AuTL administrations were made through the hepatic artery via a subcutaneous reservoir located at the right upper leg. Six injections were administered to both patients, repeated at 2-week intervals. The total number of administered T cells reached 2.4 x 10(9) and 3.1 x 10(9), respectively. RESULTS: A 39% and 51% regression in each infused field, compared with the size of liver tumor before treatment, was observed by computed tomography (CT) scan in patient 1 and 2, respectively. The responses continued up to the 10th and 11th month after the intraarterial infusion, confirmed by follow-up CT scan. The adverse effects of intraarterial immunotherapy were tolerable, with grade 1-2 fever and nausea in each patient. CONCLUSIONS: Clinical regression of liver metastases of esophageal cancer was observed in both patients who received this intraarterial cellular immunotherapy. Liver metastases of esophageal cancer may be controlled effectively and safely by repeating the intraarterial AuTL infusion as a locoregional immunotherapy over a long period.

Esophageal Neoplasms↗

PubMed2002

Three-field dissection for squamous cell carcinoma in the thoracic esophagus.

An esophageal cancer has frequent metastasis in the cervical and upper mediastinal lymph nodes, in particular along the recurrent nerves. Cervicothoracoabdominal three-field dissection is the most radical and rational lymphadenectomy procedure based on this evidence. During three-field dissection, the nodes along the recurrent nerves from the neck to the mediastinum are more meticulously resected than during any other procedure of radical lymphadenectomy. A consensus has been obtained that complete resection of the recurrent nerve nodes improves the survival rates of patients with cancer in each of the various locations of the thoracic esophagus, and that resection of the supraclavicular and internal jugular nodes improves the survival rates of patients with cancer in the upper thoracic esophagus. There is, however, still some controversies over whether or not resection of the supraclavicular and internal jugular nodes improves the survival rates of patients with cancer in the middle or lower thoracic esophagus. Moreover, there remains many controversies over the indication for three-field dissection regarding metastasis-positivity in the lymph nodes, the numbers of the metastasis-positive nodes, the stage, surgical risks and other aspects. Large randomized prospective studies are needed to accumulate conclusive evidence for the benefits of three-field dissection.

Carcinoma, Squamous Cell↗

PubMed2001

Imaging exocytosis of single insulin secretory granules with evanescent wave microscopy: distinct behavior of granule motion in biphasic insulin release.

To study insulin exocytosis by monitoring the single insulin secretory granule motion, evanescent wave microscopy was used to quantitatively analyze the final stage of insulin exocytosis with biphasic release. Green fluorescent protein-tagged insulin transfected in MIN6 beta cells was packed in insulin secretory granules, which appeared to preferentially dock to the plasma membrane. Upon fusion evoked by secretagogues, evanescent wave microscopy revealed that fluorescence of green fluorescent protein-tagged insulin brightened, spread (within 300 ms), and then vanished. Under KCl stimulation, which represents the 1st phase of release, the successive fusion events were seen mostly from previously docked granules for the first minute, followed by the recruitment of new granules to the plasmalemmal docking sites. Stimulation with glucose, in contrast, caused the fusion events from previously docked granules for the first 120 s, thereafter a continuous fusion (2nd phase of release) was observed over 10 min mostly from newly recruited granules that progressively accumulated on the plasma membrane. Thus, our data revealed the distinct behavior of the insulin granule motion during the 1st and 2nd phase of release.

Animals↗

PubMed2001

The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex.

The fifth component of the COP9 signalosome complex, Jab1/CSN5, directly binds to and induces specific down-regulation of the cyclin-dependent kinase inhibitor p27 (p27(Kip1)). Nuclear-cytoplasmic translocation plays an important role because leptomycin B (LMB), a chemical inhibitor of CRM1-dependent nuclear export, prevents p27 degradation mediated by Jab1/CSN5. Here we show that Jab1/CSN5 functions as an adaptor between p27 and CRM1 to induce nuclear export and subsequent degradation. Jab1/CSN5, but not p27, contains a typical leucine-rich nuclear export signal (NES) sequence conserved among different species, through which CRM1 bound to Jab1/CSN5 in an LMB-sensitive manner. Alteration of conserved leucine residues to alanine within Jab1/CSN5-NES abolished the interaction with CRM1 in vitro and impaired LMB-sensitive nuclear export and the ability to induce p27 breakdown in cultured cells. A Jab1/CSN5 truncation mutant lacking NES reversed p27 down-regulation induced by the full-length Jab1/CSN5, indicating that this mutant functions as a dominant negative (DN-Jab1). Introduction of DN-Jab1 into proliferating fibroblasts increased the level of p27 protein, thereby inducing growth arrest of the cells. Random mutagenesis analysis revealed that specific aspartic acid, leucine, and asparagine residues contained in the Jab1/CSN5-binding domain of p27 were required for interaction with Jab1/CSN5 and for down-regulation of p27. Glycerol gradient and cell fractionation experiments showed that at least two different forms of Jab1/CSN5-containing complexes existed within the cell. One is the conventional 450-kDa COP9 signalosome (CSN) complex located in the nucleus, and the other is much smaller (around 100-kDa), containing only a subset of CSN components (CSN4-8 but not CSN1-3), and mainly located in the cytoplasm. Treatment of cells with LMB greatly reduced the level of the smaller complex, suggesting that it originated from the CSN complex by nuclear export. Besides Jab1/CSN5, CSN3, -6, -7, and -8 were capable of inducing p27 down-regulation, when ectopically expressed. These results indicate that cytoplasmic shuttling regulated by Jab1/CSN5 and other CSN components may be a new pathway to control the intracellular abundance of the key cell cycle regulator.

3T3 Cells↗