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Biomedical subjects

M Tomita

Publications and source records attributed to M Tomita.

At least 19 recordsLinked to original sources
PubMed2006

Ablation of a peptidyl prolyl isomerase Pin1 from p53-null mice accelerated thymic hyperplasia by increasing the level of the intracellular form of Notch1.

Tumor suppressor p53 is essential for checkpoint control in response to a variety of genotoxic stresses. DNA damage leads to phosphorylation on the Ser/Thr-Pro motifs of p53, which facilitates interaction with Pin1, a pSer/pThr-Pro-specific peptidyl prolyl isomerase. Pin1 is required for the timely activation of p53, resulting in apoptosis or cell cycle arrest. To investigate the physiological relationship between Pin1 and p53, we created Pin1-/-p53-/- mice. These p53-deficient mice spontaneously developed lymphomas, mainly of thymic origin, as well as generalized lymphoma infiltration into other organs, including the liver, kidneys and lungs. Ablation of Pin1, in addition to p53, accelerated the thymic hyperplasia, but the thymocytes in these Pin1-/-p53-/- mice did not infiltrate other organs. The thymocytes in 12-week-old Pin1-/-p53-/- mice were CD4(-)CD8(-) (double negative) and had significantly higher levels of the intracellular form of Notch1 (NIC) than the thymocytes of p53-/- or wild-type mice. Presenilin-1, a cleavage enzyme for NIC generation from full-length Notch1 was increased in the thymocytes of Pin1-/-p53-/- mice. Pin1 depletion also inhibited the degradation of NIC by proteasomes. These results suggest that both Pin1 and p53 control the normal proliferation and differentiation of thymocytes by regulating the NIC level.

Animals↗
PubMed2006

Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53.

We previously reported that p42/SETbeta is a substrate for caspase-7 in irradiated MOLT-4 cells, and that treating the cells with sodium orthovanadate (vanadate) inhibits p42/SETbeta's caspase-mediated cleavage. Here, we initially found that the inhibitory effect of vanadate was due to the suppression of caspase activation but not of caspase activity. Further investigations revealed that vanadate suppressed upstream of apoptotic events, such as the loss of mitochondrial membrane potential, the conformational change of Bax, and p53 transactivation, although the accumulation, total phosphorylation, and phosphorylation of six individual sites of p53 were not affected. Importantly, vanadate suppressed p53-dependent apoptosis, but not p53-independent apoptosis. Finally, gel-shift and chromatin immunoprecipitation assays conclusively demonstrated that vanadate inhibits the DNA-binding activity of p53. Vanadate is conventionally used as an inhibitor of protein tyrosine phosphatases (PTPs); however, we recommend that the influence of vanadate not only on PTPs but also on p53 be considered before using it.

Apoptosis↗
PubMed2006

[New method for localization of the small ground-glass opacity lesion in resected lung].

A small lesion showing ground-glass opacity (GGO) by preoperative computed tomography (CT) is sometimes difficult to detect after lobectomy when it locates in the central part of the lobe. In order to facilitate to identify the lesion for marking pathological specimen, we developed a new method using CT. After surgery, the resected pulmonary lobe was expanded with airflow through the bronchial stump and the target lesion was examined with CT. The laser beam of the CT on the surface of the lung is used as a guiding line for cutting. Through the application of this method for 2 clinical cases, it was found to be possible to exactly identify the GGO lesion from the surface of the resected lung enabling to visualize a fresh surface of the lesion like a CT image with minimal destruction of the structure.

Aged↗
PubMed2006

[pN0 stage IA lung cancer downstaged from pN2 IIIA by induction therapy; report of a case].

A 75-year-old male of adenocarcinoma in non-small cell lung cancer (NSCLC) was diagnosed to be p-staged IIIA by a preoperative mediastinoscopy. After the induction chemotherapy of cisplatin (80 mg/m2, day 1, 4 weeks, 2 cycles) plus docetaxel hydrate (60 mg/m2, day 1, 4 weeks, 2 cycles), we performed lobectomy and lymph nodes dissection. The postoperative pathological results showed no metastasis of the resected lymph nodes. The postoperative stage has been down to be pN0 IA from pN2 IIIA. After the adjuvant therapy of docetaxel hydrate (60 mg/m2, day 1, 4 weeks, 2 cycles), the postoperative serum carcinoembryonic antigen level has been normalized without a recurrence for more than 2 years. A pathological staging with a mediastinoscopic diagnosis for the suspected clinical IIIA-staged NSCLC should bring us a good assessment of the induction therapy.

Adenocarcinoma↗
PubMed2005

Relationship between filtration coefficients of microvasculature and levels of atrial natriuretic peptide or echocardiographic measurements.

BACKGROUND/AIMS: Assessing the volume status of hemodialysis (HD) patients and determining their adequate dry weight (DW) present great challenges for physicians involved in HD. In this study the relationship between standardized filtration coefficients of microvasculature (Lpst) and the plasma atrial natriuretic peptide (ANP) levels or echocardiographic measurements (UCGm) were clarified. The aim of this study was to evaluate the possibility of utilizing Lpst as one of the tools for assessing volume status of patients undergoing HD. METHODS: 52 patients on maintenance HD were examined. Lpst was calculated by utilizing continuous measurements of blood volume during HD by means of monitoring changes of hematocrit with CRIT-LINE(TM). Plasma ANP levels were measured shortly after HD. Plasma ANP levels were elevated beyond the normal limit in 32 patients (Hi group) and were within the normal range in the remaining 20 patients (Lo group). UCGm were performed within 1 month prior to the study. Inferior vena cava diameters in quiet expiration (IVCe) were dilated in 21 patients (Hivc group) and were within the normal range in the remaining 31 patients (Livc group). Lpst was compared with plasma ANP level and UCGm. RESULTS: Lpst in Lo group were significantly lower than those in the Hi group (0.83+/-0.19 vs. 2.64+/-2.73 ml/mm Hg/min; p<0.001). Lpst correlated significantly with plasma ANP levels (r=0.613; p<0.001). Lpst in the Livc group were significantly lower than those in the Hivc group (1.33+/-1.61 vs. 2.85+/-2.88 ml/mm Hg/min; p<0.001). Lpst also correlated with IVCe (r=0.630; p<0.001). The receiver operating characteristic (ROC) curves for high plasma ANP level and for dilated IVCe were significant for Lpst. Area under the ROC curve for elevated ANP was 0.909 (95% confidence interval (CI) 0.834-0.985) and for dilated IVCe was 0.833 (95% CI 0.724-0.941). CONCLUSION: We conclude that there exists a significant association between Lpst and plasma ANP levels at the end of a dialysis session. There is a possibility that high plasma ANP levels cause elevation of Lpst. Besides ANP, Lpst significantly correlated with IVCe. These results suggested that Lpst can be utilized as one of the tools for assessing volume status of patients undergoing HD.

Adult↗
PubMed2005

Prognostic determinants for lung cancer patients with preoperative high serum carcinoembryonic antigen levels.

BACKGROUND: Several reports have indicated that preoperative high serum carcinoembryonic antigen (CEA) levels are associated with poor survival after surgical resection in lung cancer. METHODS: 82 consecutive lung cancer patients with preoperative high serum CEA levels (> 5 ng/mL) were included in this study. Postoperative serum CEA level was also measured. Prognostic indicators were evaluated. RESULTS: Among patients with a preoperative high serum CEA level, a serum CEA level higher than 10 ng/mL, pT status, pN status, and positive pleural lavage cytology findings were unfavorable prognostic indicators, whereas age, gender, smoking status, histologic subtype were not. Postoperative serum CEA levels of all but 2 patients decreased, however those of 28 patients did not return to normal range. Our result showed that patients with postoperative high serum CEA level had poor prognosis. Multivariate analysis demonstrated that pT status, pN status, and postoperative high serum CEA level was an independent prognostic determinant. CONCLUSIONS: In lung cancer patients with preoperative high serum CEA levels, pT status, pN status, and normalization of serum CEA level after surgery are significant prognostic determinants.

Adenocarcinoma↗
PubMed2005

[Primary lung cancer; assessment of the disclosed 5-year survival rate by the Internet website].

The disclosed 5-year survival rate for lung cancer in the Internet website represents a various difference by each institution. The better inferiority of the survival has been listed in a table to compare with other institutions and has been reported in magazines and media with a lack of an enough inspection, i.e., with a sufficient considering of a risk adjustment such as patient's background, operative policy, postoperative adjuvant therapy, and statistical background. We report our outcome of the surgical treatment for primary lung cancer. Of 875 patients treated for lung cancer in our department for 23 years between January 1980 and December 2002, 115 patients containing of 42 cases in 1997 and of 48 ones in 1992 and of 25 ones in 1987 were selected and the accumulated survival analysis was treated by Kaplan-Meier method. Eighty males and 35 females were between 15 and 80-year-old (average 63.2 +/- 11.4). The pathological classification was adenocarcinoma (n=69), squamous cell carcinoma (n=32), and others (n=14). The operative procedures were pneumonectomy (n=14), bilobectomy (n=12), lobectomy (n=85), and wedge resection (n=4). The survival time was from 29 days to 182 months (median survival time was 1471+/- 1180 days, the averaged time was 49 months). The 5-year survival rate was 41.4 +/- 9.1% (n=25) in 1987, 35.6 +/- 6.2% (n=48) in 1992, and 56.0 +/- 7.0% (n=42) in 1987, respectively (log-rank test, p = 0.2555). The 10-year survival rate was 24.1 +/- 7.9% in 1987 and 8.5 +/- 3.6% in 1992, respectively. The 5-year survival rate was as follows: IA 81.0 +/- 8.6% (n=20), IB 73.7 +/- 10.1% (n=19), IIA 57.1 +/- 18.7% (n=7), IIB 55.6 +/- 16.6% (n=9), IIIA 28.6 +/- 7.6% (n=35), IIIB 15.4 +/- 10.0% (n=13), IV 16.7 +/- 10.8% (n=12), respectively. The 5-year survival rate was as follows: male 42.8 +/- 5.3% (n=80), female 63.2 +/- 7.3% (n=35), respectively (p = 0.0147). In regard to the histological classification, the 5-year survival rate was as follows: adenocarcinoma 47.2 +/- 5.9% (n=69), squamous cell carcinoma 50.8 +/- 8.9% (n=32), respectively (p = 0.9012). As a rule of the disclosure on the internet website, we report our survival data by accompanying with minimum parameters such as, patient's background, pathological types, gender, pathological stages, and mean survival rate with standard error. When we compare the 5-year survival rate with other institutes, in considering of a risk adjustment, we would carefully have to estimate the determined survival rate with a standard error.

Adenocarcinoma↗
PubMed2005

[Surgery for the thymoma combined with pure red cell aplasia and myasthenia gravis].

UNLABELLED: Pure red cell aplasia (PRCA) and myasthenia gravis (MG) are respectively combined with thymoma, however, these 3 complications are extremely rare coexisted as a clinical triad. A 73-year-old female with mediastinal tumor found in 2000 was pointed out anemia in June 2002. As PRCA was diagnosed by the bone marrow examination, blood transfusion had been performed. By a chest computed tomography (CT), a thymoma in size of 7 x 5 cm in diameter was recognized in the anterior mediastinum. The serum level of anti-acetylcholine receptor antibody was elevated to be 35 nmol/l. MG was simultaneously diagnosed with a decreased power of neck muscle. The extended thymectomy was performed in August 2002, and pathological diagnosis disclosed a 'type AB' by World Health Organization (WHO) classification. After the operation, the decreased power of neck muscle had been improved, however, PRCA had not been remitted in the early-postoperative term. Blood transfusion had been required (2-4 units/1-2 weeks) for the postoperative 7 months' term. A cyclosporin (250 mg/day) as an adjuvant therapy was administered in April 2003. One month later, the patient's serum level of Hb had been over 10 g/dl without blood transfusion. The patient has been followed up with reducing the dose of cyclosporin. CONCLUSIONS: Surgery for a thymoma combined with PRCA and MG was effective for MG but not for PRCA in an early-postoperative term, however, a multimodality therapy with immunosuppressant as a postoperative adjuvant should bring a favorable outcome to patient's clinical data, and the postoperative long-observation must be critical in this case.

Aged↗
PubMed2004

Effects of vitamin D and estrogen receptor gene polymorphisms on the changes in lumbar bone mineral density with multiple pregnancies in Japanese women.

BACKGROUND: Our aims were to follow the longitudinal changes in lumbar spine bone mineral density (BMD) with multiple pregnancies, and to study whether polymorphisms in the vitamin D receptor (VDR) and estrogen receptor (ER) genes may influence the results. METHODS: We repeatedly measured the BMD of the lumbar spine (L2-L4) of 133 women who had undergone two successive pregnancies and 73 non-pregnant controls, and analysed the restriction fragment length polymorphisms using restriction endonucleases TaqI, ApaI and FokI for the VDR gene, and PvuII and XbaI for the ER gene. RESULTS: Cases and controls had no significant differences in the longitudinal BMD changes. The mean percentage change in lumbar BMD (DeltaBMD%) of the women with the XX/Xx genotype was significantly lower than that of the women with the xx genotype after adjusting for age at each delivery, BMD of the first scan, and interval between the scans (0.2 +/- 3.3 versus 2.0 +/- 4.2%; P=0.030, analysis of covariance). Multiple regression analyses to evaluate the contribution of the XbaI polymorphism of the ER gene on DeltaBMD% showed that the percentage decrease in BMD was greater for women lacking the XbaI restriction site (adjusted R2=0.188, P<0.0001). CONCLUSIONS: The present study suggests that the DeltaBMD% was significantly influenced by the XbaI polymorphism of the ER gene.

Adult↗
PubMed2003

The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models.

MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/

Database Management Systems↗
PubMed2003

G-language Genome Analysis Environment: a workbench for nucleotide sequence data mining.

SUMMARY: G-language Genome Analysis Environment (G-language GAE) is an open source generic software package aimed for higher efficiency in bioinformatics analysis. G-language GAE has an interface as a set of Perl libraries for software development, and a graphical user interface for easy manipulation. Both Windows and Linux versions are available. AVAILABILITY: From http://www.g-language.org/ under GNU General Public License. CD-ROMs are distributed freely in major conferences.

Database Management Systems↗
PubMed2003

Astroglial swelling in the neuronal depolarization ensemble.

The coupling between neuronal depolarization and astroglial swelling was examined. First, previous in vitro data for the swelling of cultured neurons (N18; rat neuroblastoma) and astroglia (C6; rat astroglyoma) upon exposure to a hypoosmotic solution were reappraised. Neurons swelled rapidly, forming blisters, and easily burst. whereas astroglia resisted swelling and slowly assumed a large full-moon shape. The time constant of swelling was 35.2 +/- 7.8 s for N18 and 594.8 +/- 554.0 s for C6. The glial plasmic membrane was found to be much stronger than the neuronal one, presumably due to a well-developed cytoskeleton. To overcome such neuronal membranous weakness, strong astroglial processes need to cover the neurons including the cell body and synapses, as demonstrated electron-microscopically. Next, in situ astroglial swelling was investigated in rats. During K(+)-induced cortical spreading depression, increases or decreases of a wave-ring spread of light (550 nm) transmission through a 1 mm-thick cerebral cortical layer was observed. The moving local optical density decrease in the cortex was attributable to local vascular bed compression induced by astroglial swelling, since concomitant occurrence of colocated dynamic capillary flow stall was confirmed by a hemodilution technique. Astroglial swelling may occur in an ensemble acting during neuronal depolarization, suggesting that neurons and astroglia behave like a unit complex.

Animals↗
PubMed2003

Comparative study of translation termination sites and release factors (RF1 and RF2) in procaryotes.

Translation termination is catalyzed by release factors that recognize stop codons. However, previous works have shown that in some bacteria, the termination process also involves bases around stop codons. Recently, Ito et al. analyzed release factors and identified the amino acids therein that recognize stop codons. However, the amino acids that recognize bases around stop codons remain unclear. To identify the candidate amino acids that recognize the bases around stop codons, we aligned the protein sequences of the release factors of various bacteria and searched for amino acids that were conserved specifically in the sequence of bacteria that seemed to regulate translation termination by bases around stop codons. As a result, species having several highly conserved residues in RF1 and RF2 showed positive correlations between their codon usage bias and conservation of the bases around the stop codons. In addition, some of the residues were located very close to the SPF motif, which deciphers stop codons. These results suggest that these conserved amino acids enable the release factors to recognize the bases around the stop codons.

Amino Acid Sequence↗
PubMed2003

Prognostic significance of bcl-2 expression in resected pN2 non-small cell lung cancer.

AIMS: The prognosis of non-small cell lung cancer with pathologic mediastinal lymph node involvement (pN2) is poor, we wished to study the expression of p53, bcl-2 by immunohistochemistry in a series of such patients. METHODS: Clinicopathologic factors were investigated in relation to prognosis in 60 patients with resected pN2 non-small cell lung cancer. RESULTS: The 5-year survival rate was 21.7%. Positive staining for p53, and bcl-2 was found in 29/60 and 12/60, respectively. Patients with bcl-2 positive tumor had a more favorable survival than those with bcl-2 negative tumor (P=0.0054). The expression of p53 was not related to patients' survival. Multivariate analysis showed that Bcl-2 expression and single N2 station were independent prognostic factors. CONCLUSIONS: Patients with bcl-2 positive tumors may comprise a favorable prognostic subgroup in pN2 non-small cell lung cancer.

Adult↗