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Biomedical subjects

Takashi Watanabe

Publications and source records attributed to Takashi Watanabe.

At least 109 records · Page 6Linked to original sources
PubMed2004

T(11;18)-bearing pulmonary mucosa-associated lymphoid tissue lymphoma responding to cladribine.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B-cell lymphoma and is usually slow to disseminate. The t(11;18)(q21;q21) translocation has been identified in a subset of MALT lymphoma cases, and AP12 and MLT1/MALT1 genes have been implicated in this translocation. However, the clinicopathologic features of t(11;18)-bearing MALT lymphoma have not been fully elucidated, and the optimal therapy for patients with disseminating disease is unknown. We report an outstanding case of MALT lymphoma that showed massive pulmonary infiltration and leukemic transformation during a prolonged course of more than 16 years. Reverse transcriptase-polymerase chain reaction and dual-color fluorescence in situ hybridization analyses confirmed the existence of the AP12/MLT1 fusion gene in the lymphoma cells. Peripheral blood lymphoma cells disappeared after glucocorticoid therapy. Although the pulmonary lymphoma was slowly progressive and caused severe hypoxemia despite the continuation of glucocorticoid therapy, treatment with cladribine induced a marked reduction of pulmonary lymphomatous lesions and an improvement of the hypoxemia. These findings show the unique clinical features of this particular indolent B-cell lymphoma with t(11;18) translocation and suggest the potential therapeutic usefulness of glucocorticoid and cladribine.

Adult↗
PubMed2004

Primary mediastinal large B-cell lymphoma: a single-institution clinical study in Japan.

Several clinicopathologic studies of primary mediastinal large B-cell lymphoma (Med-DLBCL) have been reported from Western countries; however, only a few series of at most 10 cases are available in Japan. To further clarify the Med-DLBCL occurring in Japan, we analyzed the clinical features of 28 patients with Med-DLBCL diagnoses who were treated at the National Cancer Center Hospital between 1982 and 2002. The median age was 37 years (range, 18-80 years). The ages of 16 male patients ranged widely from 18 to 80 years, whereas the 12 female patients appeared to show a single age peak at 20 to 40 years. Only 13 patients (46%) achieved a complete response with initial treatments, mostly by CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisolone) followed by radiotherapy. The estimated 3-year overall and failure-free survival rates were 32% and 33%, respectively, indicating the relatively unfavorable prognosis of the patients in our series. The following factors were found to be significantly associated with shortened survival prospects: age >60 years, serum lactate dehydrogenase level greater than normal, performance status >1, and presence of bulky mediastinal mass. In conclusion, the clinical features of Japanese patients with Med-DLBCL may be different from those with the disease in Western countries. Because this investigation was a single-institution study with a limited number of patients, however, multicenter confirmatory studies are needed.

Adolescent↗
PubMed2004

EBV-positive Burkitt lymphoma as a late-onset posttransplantion lymphoproliferative disorder after allogeneic stem cell transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is one of the well-recognized complications after allogeneic stem cell transplantation (SCT). It generally occurs early after SCT, and only a few reports of late-onset cases are available. We report a 58-year-old male patient who developed lymphoma 4 years after allogeneic SCT for chronic myeloid leukemia. The presence of c-myc translocation and Epstein-Barr virus-encoded RNA in the lymphoma cells, without rearrangement of the 3'-bcr region, confirmed the histopathologic diagnosis of Burkitt lymphoma. DNA chimerism analysis revealed that the lymphoma cells were of donor origin. The patient achieved complete response with intensive chemotherapy. To our knowledge, this is the first report of Burkitt lymphoma as a PTLD occurring after allogeneic SCT.

Burkitt Lymphoma↗
PubMed2004

Two entities of precursor T-cell lymphoblastic leukemia/lymphoma based on radiologic and immunophenotypic findings.

Precursor T-cell lymphoblastic leukemia/lymphoma (T-ALL/LBL) presents a mediastinal mass in one half of cases. Although the immunophenotypic features of T-ALL/LBL have been analyzed in several studies, few studies have been focused on the relationship between the anatomic distribution of lesions and immunophenotypic findings. We analyzed the clinicopathologic findings for 17 patients with T-ALL/LBL diagnosed since 1993 and whose radiologic findings were available. Data on 14 men and 3 women with a median age of 26 years (range, 10-61 years) were analyzed. On the basis of radiologic findings, the cases were divided into thymic type (n = 8) and nonthymic type (n = 9). Patients with the thymic type of T-ALL/LBL had a large mediastinal mass and minimal systemic lymphadenopathy only in the supradiaphragmatic region. Those with the non-thymic type had predominantly systemic lymphadenopathy that included infradiaphragmatic lesions. Expression of CD8 (6/7 versus 0/9) was more frequently found in the thymic type (P < .001), whereas expression of CD56 (0/7 versus 5/9) was more frequent in the nonthymic type (P = .034). In conclusion, T-ALL/LBL was divided into 2 entities, thymic type and nonthymic type, on the basis of radiologic findings and immunophenotypic features. Analysis of the expression of CD8 and CD56 would be useful for biologically classifying T-ALL/LBL into the 2 types. This study was performed in a single institution, was retrospective, and had a limited number of patients; multicenter confirmatory studies are warranted.

Adolescent↗
PubMed2004

Transcranial electrical stimulation through screw electrodes for intraoperative monitoring of motor evoked potentials. Technical note.

The feasibility of high-frequency transcranial electrical stimulation (TES) through screw electrodes placed in the skull was investigated for use in intraoperative monitoring of the motor pathways in patients who are in a state of general anesthesia during cerebral and spinal operations. Motor evoked potentials (MEPs) were elicited by TES with a train of five square-wave pulses (duration 400 microsec, intensity < or = 200 mA, frequency 500 Hz) delivered through metal screw electrodes placed in the outer table of the skull over the primary motor cortex in 42 patients. Myogenic MEPs to anodal stimulation were recorded from the abductor pollicis brevis (APB) and tibialis anterior (TA) muscles. The mean threshold stimulation intensity was 48 +/- 17 mA for the APB muscles, and 112 +/- 35 mA for the TA muscles. The electrodes were firmly fixed at the site and were not dislodged by surgical manipulation throughout the operation. No adverse reactions attributable to the TES were observed. Passing current through the screw electrodes stimulates the motor cortex more effectively than conventional methods of TES. The method is safe and inexpensive, and it is convenient for intraoperative monitoring of motor pathways.

Adolescent↗
PubMed2004

Comparative analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in gastric and colorectal cancers.

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are considered to be key enzymes affecting the prognosis for patients with gastric and colorectal cancers. We tried to prove the correlation of TP and DPD expressions in gastric and colorectal cancers. The present study was designed to quantify TP and DPD levels by an enzyme-linked immunosorbent assay (ELISA) in tumors and normal tissues obtained from 16 gastric and 20 colorectal cancer patients. TP and TP/DPD ratio in the tumor specimens were almost all higher than those in each normal tissue, especially for tumors in the progressive state. In the early stage of the colorectal cancer group, DPD in the normal tissues were higher than those in the tumor specimens. There were no significant differences between TP levels in the tumor specimens of the two groups, whereas in stages III and IV, those of the gastric cancer group tended to be higher than those of colorectal cancer group. In stages I and II, DPD levels in the tumor specimens tended to be higher in the gastric cancer group than in the colorectal cancer group. DPD T/N was higher in the gastric cancer group than in the colorectal cancer group. There were no significant differences between TP/DPD ratios in the tumor specimens of the two groups, whereas those in normal tissue were higher in the gastric cancer group than in the colorectal cancer group. We may be able to achieve the successful effects or reduction of side effects of anticancer chemotherapy for gastric and colorectal cancer using the results of this study.

Aged↗
PubMed2004

[MR imaging study of edema along the optic tract in patient with Rathke's cleft cyst].

We report an 80-year-old woman who was admitted to our hospital with symptoms due to diabetes insipidus. Magnetic resonance (MR) imaging demonstrated a sellar/suprasellar cystic lesion with marginal enhancement and the thick pituitary stalk. The MR imaging depicted edema spreading along the optic tract on fluid-attenuated inversion recovery (FLAIR) images. Upon neurological examination at the time of admission, there were no abnormal findings affecting the field of vision or visual acuity. In endocrinological examination, the basal plasma values of pituitary hormones were within normal range except for that of prolactin, which was 47.9 ng/ml. The preoperative diagnosis was craniopharyngioma, and the intrasellar mass was partially removed by the endoscopic transnasal transsphenoidal approach. Postoperative histopathological examination revealed Rathke's cleft cyst associated with squamous metaplasia. Lymphocytic infiltration was also confirmed in both the anterior and posterior pituitary lobe. The postoperative course was satisfactory. Edema spreading along the optic tract was reported as a characteristic MR imaging finding for diagnosis of craniopharyngiomas or optic nerve glioma. However, it is suggested that edema of the optic pathway seems to be caused not only by craniopharyngioma but also other suprasellar lesions. It was a rare case of secondary lymphocytic hypophysitis caused by Rathke's cleft with edema along the optic tract.

Aged↗
PubMed2004

Preoperative endoscopic analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase in gastrointestinal cancer.

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are considered to be key enzymes affecting the prognosis for patients with advanced gastrointestinal cancer. Preoperative examination of TP and DPD expression levels and assessment of these enzymes in inoperable cancer patients may contribute to successful treatment. We tried to prove the correlation of TP and DPD expression in preoperative specimens by endoscopy and in surgical specimens. The present study was designed to quantify TP and DPD levels by enzyme-linked immunosorbent assay (ELISA) in tumor tissue obtained from 30 gastrointestinal cancer patients by preoperative endoscopy and surgery, including 15 gastric and 15 colorectal cancers. Successful cases as those in which cancer cells were demonstrated histologically in preoperative specimens by endoscopy were 12 (success rate: 80%) in gastric cancer patients, and 15 (success rate: 100%) in colorectal cancer patients. In successful cases, there were almost significant correlations in all cases, gastric cancer, and colorectal cancer among the expression of TP, DPD, and TP/DPD ratio in each preoperative specimen by endoscopy and surgical specimen, respectively. On the other hand, in the gastric cancer group, 3 unsuccessful cases resulted in a significant departure from ideal equation compared with 12 successful cases. In actual clinical care, physicians should pay attention to and evaluate carefully the data from endoscopical biopsy specimens in which cancer cells may not be demonstrated histologically. Thus, endoscopic analysis of TP and DPD expression in preoperative or inoperable cancer patients may contribute to successful treatment.

Aged↗
PubMed2004

Transoral penetration of a half-split chopstick between the basion and the dens.

A 6-year-old girl was admitted for transoral penetrating injury by a half-split chopstick. Subsequent CT imaging examinations showed that the chopstick had passed between the basion and the dens and reached the subarachnoid space just at the medulla oblongata. A sagittal reconstructed CT scan was useful for the evaluation of the injury. Imaging findings and their clinical relevance are discussed.

Brain Injuries↗
PubMed2004

Thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in hepatocellular carcinoma and metastatic liver cancer.

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are considered to be key enzymes affecting the prognosis for patients with various cancers. We tried to prove the correlation of TP and DPD expression in hepatocellular carcinoma (HCC) and liver metastasis. We quantified TP and DPD levels by an enzyme-linked immunosorbent assay (ELISA) in the tumor (T) and adjacent normal tissue (N) obtained from 8 HCC patients, and 11 liver metastasis patients together with 9 of their primary cancers. TP levels were higher in the primary cancer, liver metastasis, and HCC compared with each adjacent tissue. TP levels were higher in HCC than in liver metastasis, and TP levels in the adjacent tissues of HCC were also higher than those in adjacent tissues of liver metastasis. TP levels were higher in liver metastasis than in primary cancer, and TP levels in adjacent tissues of liver metastasis were also higher than those in adjacent tissues of primary cancer. However, there were no differences in TP T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. DPD levels were lower in the liver metastasis compared with the adjacent liver tissues, and DPD levels in liver metastasis or its adjacent liver tissues were higher than those in primary cancer or its adjacent tissues. There were no differences in DPD T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. Thus, we demonstrated that TP was highly expressed in liver malignancy. We may be able to increase the success of anticancer chemotherapy for liver malignancy while decreasing the side effects by analysis of T/N ratios in TP, DPD, and TP/DPD in addition to TP expression.

Aged↗
PubMed2004

Increased expression of thymidine phosphorylase in tumor tissue in proportion to TP-expression in primary normal tissue.

Thymidine phosphorylase (TP) is considered to be a key enzyme affecting the prognosis of patients with advanced gastrointestinal cancer. We tried to demonstrate the correlation of TP expression in tumor tissue and adjacent normal tissue, that is, primary normal tissue. The present study was designed to quantify TP level by enzyme-linked immunosorbent assay (ELISA) in tumor tissue and adjacent normal tissue obtained from 42 hepato-gastrointestinal cancer patients including 15 with gastric, 19 with colorectal and 8 with hepatocellular carcinomas. TP levels in tumor tissues were higher than those in adjacent normal tissues (p<0.001). There was a significant correlation between the expression of TP in tumor tissue and adjacent normal tissue (R=0.711, p<0.001; y=23.420+1.534x). On the other hand, there was no significant correlation between the ratio of tumor to adjacent normal tissue levels of TP (TP T/N) and expression of TP in tumor tissue (R=0.250, p=0.110). Thus, TP expression in tumor tissue may be high in proportion to TP expression in primary tissue. Furthermore, in clinical care, not only TP level in tumor tissue but also TP T/N value should be considered when using anticancer agents that become effective after conversion by TP to the active drug 5-FU.

Antimetabolites, Antineoplastic↗
PubMed2003

Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at sites of cell-cell contact.

The small guanosine triphosphatase Rac1 is activated by E-cadherin-mediated cell-cell adhesion and is required for the accumulation of actin filaments, E-cadherin, and beta-catenin at sites of cell-cell contact. However, the modes of activation and action of Rac1 remain to be clarified. We here found that suppression of IQGAP1, an actin-binding protein and an effector of Rac1, by small interfering RNA apparently reduced the accumulation of actin filaments, E-cadherin, and beta-catenin at sites of cell-cell contact in Madin-Darby canine kidney II epithelial cells under the conditions in which knockdown of Rac1 reduced them. Knockdown of Rac1 did not affect the localization of these junctional components in cells expressing a constitutively active IQGAP1 mutant defective in Rac1/Cdc42 binding. Knockdown of either Rac1 or IQGAP1 accelerated the 12-O-tetradecanoylphorbol-13-acetate-induced cell-cell dissociation. The basal Rac1 activity, which was maintained by E-cadherin-mediated cell-cell adhesion, was inhibited in the IQGAP1-knocked down cells, whereas the Rac1 activity was increased in the cells overexpressing IQGAP1. Together, these results indicate that Rac1 enhances the accumulation of actin filaments, E-cadherin, and beta-catenin by acting on IQGAP1 and suggest that there exists a positive feedback loop comprised of "E-cadherin-mediated cell-cell adhesion --> Rac1 activation --> actin-meshwork formation by IQGAP1 --> increasing E-cadherin-mediated cell-cell adhesion."

Actin Cytoskeleton↗
PubMed2003

Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene.

A number of chromosomal abnormalities including 19q deletions have been associated with the formation of human gliomas. In this study, we employed a proteomics-based approach to identify possible genes involved in glioma tumorigenesis which may serve as potential diagnostic molecular markers for this type of cancer. By comparing protein spots from gliomas and non-tumor tissues using two-dimensional (2D) gel electrophoresis, we identified 11 up-regulated proteins and four down-regulated proteins in gliomas. Interestingly, we also discovered that a group of cytoskeleton-related proteins are differentially regulated in gliomas, suggesting the involvement of cytoskeleton modulation in glioma pathogenesis. We then focused on the cytoskeleton-related protein, SIRT2 (sirtuin homologue 2) tubulin deacetylase, which was down-regulated in gliomas. SIRT2 is located at 19q13.2, a region known to be frequently deleted in human gliomas. Subsequent Northern blot analysis revealed that RNA expression of SIRT2 was dramatically diminished in 12 out of 17 gliomas and glioma cell lines, in agreement with proteomic data. Furthermore, ectopic expression of SIRT2 in glioma cell lines led to the perturbation of the microtubule network and caused a remarkable reduction in the number of stable clones expressing SIRT2 as compared to that of a control vector in colony formation assays. These results suggest that SIRT2 may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network and may serve as a novel molecular marker for gliomas. Additional proteins were also identified, whose function in gliomas was previously unsuspected.

Blotting, Northern↗
PubMed2003

Calpain induces proteolysis of neuronal cytoskeleton in ischemic gerbil forebrain.

We investigated the relationship between the activity of calcium-dependent protease (calpain) and the ischemic neuronal damage. We also investigated the mechanism of ischemic resistance in astrocytes. In gerbil, a 10-min forebrain ischemia was induced by occlusion of both common carotid arteries. The calpain-induced proteolysis of cytoskeleton (fodrin) was examined by immunohistochemistry. Immunolocalization of micro and m-calpain was also examined. Intact fodrin was observed both in neurons and astrocytes, but proteolyzed fodrin was not observed in normal brain. Fifteen minutes after ischemia, proteolysis of fodrin took place in putamen, parietal cortex and hippocampal CA1. The proteolysis extended to thalamus 4 h after ischemia after which the immunoreactivity faded down in all areas except hippocampus. On day 7, the proteolysis was still observed only in hippocampus. Neurons with the proteolysis of soma resulted in neuronal death. Throughout the experiment, the proteolysis was not observed in astrocytes. micro -Calpain was observed only in neurons but m-calpain was observed both in neurons and astrocytes. The ischemia induced only micro -calpain activation, which resulted in fodrin proteolysis of neurons with differential spatial distribution and temporal course. The proteolysis was developed rapidly and was completed within 24 h in all vulnerable regions except hippocampal CA1. The proteolysis preceded the neuronal death. The mechanism of the proteolysis seemed to be involved by Ca(2+) influx via glutamate receptor and rapid neuronal death seemed reasonable. The reason why neuronal death in CA1 evolved slowly was not clarified. In astrocytes, fodrin was not proteolyzed by m-calpain. The low Ca(2+)-sensitivity of m-calpain may be the reason of ischemic resistance in astrocytes.

Animals↗
PubMed2003

Bioorganosolve pretreatments for simultaneous saccharification and fermentation of beech wood by ethanolysis and white rot fungi.

Ethanol was produced by simultaneous saccharification and fermentation (SSF) from beech wood chips after bioorganosolve pretreatments by ethanolysis and white rot fungi, Ceriporiopsis subvermispora, Dichomitus squalens, Pleurotus ostreatus, and Coriolus versicolor. Beech wood chips were pretreated with the white rot fungi for 2-8 weeks without addition of any nutrients. The wood chips were then subjected to ethanolysis to separate them into pulp and soluble fractions (SFs). From the pulp fraction (PF), ethanol was produced by SSF using Saccharomyces cerevisiae AM12 and a commercial cellulase preparation, Meicelase, from Trichoderma viride. Among the four strains, C. subvermispora gave the highest yield on SSF. The yield of ethanol obtained after pretreatment with C. subvermispora for 8 weeks was 0.294 g g(-1) of ethanolysis pulp (74% of theoretical) and 0.176 g g(-1) of beech wood chips (62% of theoretical). The yield was 1.6 times higher than that obtained without the fungal treatments. The biological pretreatments saved 15% of the electricity needed for the ethanolysis.

Basidiomycota↗
PubMed2003

O6-methylguanine-DNA methyltranspherase gene expression in gliomas by means of real-time quantitative RT-PCR and clinical response to nitrosoureas.

O(6)-methylguanine-DNA methyltransferase (MGMT) mRNA expressions were examined in 100 neuroepithelial tumors by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using SYBR Green I. The mean relative quantitation value of MGMTmRNA normalized to the level of beta2-microglobulin for 100 tumors was 5.3 +/- 11.2. The mean value of 41 glioblastomas was significantly higher than that for the other 59 tumors (p = 0.0008 by Student's t-test). In contrast, the means of 19 low-grade gliomas and 12 medulloblastomas were significantly lower than that of other tumors (p = 0.0282 and p = 0.0456 by Student's t-test). Among the 55 retrospective patients who had been treated with 1-(4-amino-2-methyl-5-pyrimidynyl)methyl-3-(2-chloroethyl)- 3-nitrosourea hydrochloride (ACNU), the value was a significant independent predictor of the effect of initial therapy with ACNU (p = 0.0007 by Mann-Whitney U-test) and the survival period (p = 0.0175 by Wald test). The value >or=1 was the most significant factor in predicting the initial effect of treatment by multi-variant regression analysis (p < 0.0001). These results suggest that our individual adjuvant therapy based on MGMTmRNA expression may be improved by the application of real-time quantitative RT-PCR.

Adult↗