Biomedical subjects

Takashi Watanabe

Publications and source records attributed to Takashi Watanabe.

At least 73 records · Page 4Linked to original sources

PubMed2005

Multidetector computed tomography versus coronary angiogram in evaluation of coronary artery bypass grafts.

BACKGROUND: The new evolving multidetector computed tomography (MDCT) is thought to be promising in imaging of coronary disease. We compared the evaluating power of MDCT to that of conventional coronary artery angiogram in patients with coronary artery bypass grafting surgery. METHODS: From April 2002 to December 2003, 50 patients underwent both MDCT and coronary artery angiogram after coronary artery bypass surgery. Overall, 170 grafts were studied. Two weeks after the surgery, 8-row MDCT was taken using contrast medium to observe the grafts patency. Three weeks after the surgery, conventional coronary angiogram was done to verify the graft status. The graft status was classified according to Fitzgibbon classification. Sensitivity, positive predictive value, and negative predictive value were calculated and compared. RESULTS: Multidetector computed tomography succeeded in high-quality imaging of all grafts except for one (less than 1 mm gastroepiploic graft to posterior descending artery). This graft was the only graft that was interpreted differently. Overall patency rate was 97.8%. The diagnostic power of MDCT was as follows: the specificity was 99.4%, the sensitivity was 100%, the positive predictive value was 100%, and the negative predictive power was 80%. CONCLUSIONS: In this study, 8-row MDCT showed reliable imaging power in verifying grafts status. Since MDCT is much less invasive for patients, conventional coronary artery angiogram will be substituted by evolving MDCT.

Aged↗

PubMed2005

Akt/PKB regulates actin organization and cell motility via Girdin/APE.

The serine/threonine kinase Akt (also called protein kinase B) is well known as an important regulator of cell survival and growth and has also been shown to be required for cell migration in different organisms. However, the mechanism by which Akt functions to promote cell migration is not understood. Here, we identify an Akt substrate, designated Girdin/APE (Akt-phosphorylation enhancer), which is an actin binding protein. Girdin expresses ubiquitously and plays a crucial role in the formation of stress fibers and lamellipodia. Akt phosphorylates serine at position 1416 in Girdin, and phosphorylated Girdin accumulates at the leading edge of migrating cells. Cells expressing mutant Girdin, in which serine 1416 was replaced with alanine, formed abnormal elongated shapes and exhibited limited migration and lamellipodia formation. These findings suggest that Girdin is essential for the integrity of the actin cytoskeleton and cell migration and provide a direct link between Akt and cell motility.

Actins↗

PubMed2005

A non-NF2 case of schwannomas of vestibular and trigeminal nerves with different genetic alterations of NF2 gene: case report.

BACKGROUND: We report a patient with 2 separate schwannomas, a vestibular schwannoma and a trigeminal schwannoma, that were attached to each other and appeared to be a single tumor on imaging studies. CASE DESCRIPTION: The patient, without any family history of neurofibromatosis, presented with a progressive hearing loss and mild left facial nerve palsy. Magnetic resonance imaging showed a snowman-like tumor in the left cerebellopontine angle. Surgical exposure revealed that the tumor consisted of 2 "kissing" schwannomas, a trigeminal and vestibular schwannoma. Molecular genetic analysis detected a 1-base pair deletion at exon 10 of the neurofibromatosis type 2 (NF2) gene in the trigeminal schwannoma, but not in the acoustic schwannoma. However, loss of heterozygosity at chromosome 22q (D22S282 and D22S929) was detected in both tumors, losing the same allele. CONCLUSION: Multiple schwannomas in non-NF2 patients are extremely rare, and possible causes include simple coincidence or germline genetic alteration of adjacent gene on chromosome 22q, similar to the cause recently suggested in familial schwannomatosis. Although not always possible, molecular genetic examination may help to understand the underlying mechanism and would be warranted in such cases.

Chromosomes, Human, Pair 22↗

PubMed2005

Regulation of microtubules in cell migration.

Directional cell migration is a fundamental process in all organisms that is stringently regulated during tissue development, chemotaxis and wound healing. Migrating cells have a polarized morphology with an asymmetrical distribution of signaling molecules and the cytoskeleton. Microtubules are indispensable for the directional migration of certain cells. Recent studies have shown that Rho family GTPases, which are key regulators of cell migration, affect microtubules, in addition to the actin cytoskeleton and adhesion. Rho family GTPases capture and stabilize microtubules through their effectors at the cell cortex, leading to a polarized microtubule array; in turn, microtubules modulate the activities of Rho family GTPases. In this article, we discuss how a polarized microtubule array is established and how microtubules facilitate cell migration.

Animals↗

PubMed2005

Cloning of rat p47phox and comparison with human p47phox.

A cDNA encoding rat p47phox was cloned from rat spleen cDNA library, utilizing rapid amplification of cDNA ends. The open reading frame corresponded to 389 amino acids: It contained the phagocyte oxidase homology domain, two Src homology 3 domains and a proline rich region, all of which are conserved in mammalian p47phox sequences. Rat p47phox displayed the highest degree of identity to mouse p47phox (94%). We expressed and purified rat p47phox as a glutathione S-transferase fusion protein, and found that the rat protein could replace human p47phox in a cell-free activation system for human NADPH oxidase, giving about half activity. Although rat 12-lipoxygenase interacted with human p47phox in a yeast two-hybrid system, this was not the case for rat p47phox.

Amino Acid Sequence↗

PubMed2005

CD56-positive small round cell tumor: osseous plasmacytoma manifested in osteolytic tumors of the iliac bone and femora.

Monoclonal gammopathy of undetermined significance does not overexpress cluster of differentiation (CD) 56, but plasma cell myeloma frequently overexpressed it. However, plasma cell leukemia and extramedullary plasmacytoma usually down-regulate CD56 expression. Plasmacytoma, especially 'solitary plasmacytoma of bone', is difficult to diagnose as plasma cell neoplasm, because it occasionally appears similar to other bone tumors, both clinically and pathologically, and is rarely accompanied by monoclonal protein in the serum or urine. The present case was a patient with an osteolytic 'small round cell tumor' of the iliac bone, which also invaded the femora. An immunohistopathological finding of CD56 expression played a key role in making a diagnosis. The definitive diagnosis of plasmacytoma was made based on the electron microscopic findings. The plasma cells which infiltrated her sternum showed the same restriction to kappa light chain expression in their cytoplasms as that of the iliac bone tumor cells, but did not express CD56. Locally infiltrating osteolytic bone tumors should be examined for surface immunoglobulin light chains as well as CD56 expression when plasmacytoma is suspected.

Adult↗

PubMed2005

Noninvasive measurement of heartbeat, respiration, snoring and body movements of a subject in bed via a pneumatic method.

We have developed a noninvasive pneumatics-based system by which to measure heartbeat, respiration, snoring, and body movements of a subject in bed. A thin, air-sealed cushion is placed under the bed mattress of the subject and the small movements attributable to human automatic vital functions are measured as changes in pressure using a pressure sensor having an almost flat frequency response from 0.1 to 5 kHz and a sensitivity of 56 mV/Pa. Using the newly developed system, heartbeat, respiration, apnea, snoring and body movements are clearly measured. In addition, the optimal signal-to-noise (S/N) ratio by which to evaluate the reliability of the heart rate measurement is presented. Heart rates were measured for four different body postures, 13 different subjects, four different bed mattresses, and three different sensor positions. For these measurements, the S/N ratios ranged from 15.9 to 23.5 dB, and so were determined to be reliable.

Beds↗

PubMed2005

Joint angle control by FES using a feedback error learning controller.

The feedback error learning (FEL) scheme was studied for a functional electrical stimulation (FES) controller. This FEL controller was a hybrid regulator with a feedforward and a feedback controller. The feedforward controller learned the inverse dynamics of a controlled object from feedback controller outputs while control. A four-layered neural network and the proportional-integral-derivative (PID) controller were used for each controller. The palmar/dorsi-flexion angle of the wrist was controlled in both computer simulation and FES experiments. Some controller parameters, such as the learning speed coefficient and the number of neurons, were determined in simulation using an artificial forward model of the wrist. The forward model was prepared by using a neural network that can imitate responses of subject's wrist to electrical stimulation. Then, six able-bodied subjects' wrist was controlled with the FEL controller by delivering stimuli to one antagonistic muscle pair. Results showed that the FEL controller functioned as expected and performed better than the conventional PID controller adjusted by the Chien, Hrones and Reswick method for a fast movement with the cycle period of 2 s, resulting in decrease of the average tracking error and shortened delay in the response. Furthermore, learning iteration was shortened if the feedforward controller had been trained in advance with the artificial forward model.

Artificial Intelligence↗

PubMed2005

Follicular lymphoma subgrouping by fluorescence in situ hybridization analysis.

The frequency of t(14;18) in follicular lymphoma (FL) in Japan has been reported to be low compared to North America and other European countries. Recently, it has also been reported that FL lacks t(14;18), mainly among histological grade 3b, and occasionally has a rearranged Bcl-6 gene. It is not known whether a difference in histology or immunostaining pattern exists between FL with and without t(14;18). We performed interphase fluorescence in situ hybridization (FISH) analysis to detect Bcl-2/IgH, Bcl-6 gene rearrangement, Bcl-2 gene amplification, and the cyclinD1/IgH gene in formalin-fixed paraffin embedded specimens from our FL archives. The correlation between morphological features, histological grades, immunohistochemical findings, and cytogenetical aberrations was studied. In total, we found that 28 of 47 cases (59.6%) had t(14;18). Bcl-6 gene rearrangement and extra Bcl-2 gene signals were found in five and two cases, respectively. Only one had cyclinD1/IgH fusion. Ten of 12 grade 1, nine of 17 grade 2, and 0 of two grade 3 cases had fusion signals, respectively. None of the above abnormalities were detected in 12 of 47 cases (25.5%). Our data confirmed a high frequency of t(14;18) in FL in grade 1, but a lower incidence among grade 2, that could be attributed to the lower incidence of the translocation in FL in Japan. Immunostaining of both Bcl-2 and CD10 was highly predictable for the presence of t(14;18); the positive predictive value was 75%, suggesting the usefulness of the staining.

Adult↗

PubMed2005

Phase I study of radioimmunotherapy with an anti-CD20 murine radioimmunoconjugate ((90)Y-ibritumomab tiuxetan) in relapsed or refractory indolent B-cell lymphoma.

We conducted a phase I study to evaluate the safety and efficacy of radioimmunotherapy with yttrium-90-ibritumomab tiuxetan (Y2B8) in Japanese patients with relapsed or refractory indolent B-cell lymphoma. Indium-111-labeled ibritumomab tiuxetan (In2B8; 3.5 or 5 mCi [129.5 or 185 MBq]) was administered on day 1, followed by serial gamma-camera imaging to investigate the distribution of In2B8 in the whole body of patients and to judge the feasibility of Y2B8 administration. Y2B8 with a dose of 0.3 mCi/kg (11.1 MBq/kg) or 0.4 mCi/kg (14.8 MBq/kg) was administered on day 8. Grade 4 neutropenia and grade 3 thrombocytopenia were observed in three of nine of the patients evaluated for safety. Critical toxicities (prolonged thrombocytopenia or severe non-hematological toxicities) were observed in two of six patients in the 0.4 mCi/kg (14.8 MBq/kg) dose group but were not seen in any of the three patients in the 0.3 mCi/kg (11.1 MBq/kg) dose group. The non-hematological toxicities of the nine patients were of grade 2 or less, except in two patients who had been heavily treated previously. They experienced critical toxicities such as infection, diarrhea, hyponatremia and prolonged thrombocytopenia, as well as other frequent grade 2 non-hematological toxicities. Although the pharmacokinetic profiles were similar to those in the US study, one of the two patients was clarified retrospectively as showing abnormal biodistribution of In2B8 in the bone marrow, as judged by an independent third party panel of radiologists. Five of the 10 participants achieved complete responses or unconfirmed complete responses and two partial responses. In conclusion, the recommended dose of Y2B8 for the subsequent phase II study for Japanese patients is 0.4 mCi/kg (14.8 MBq/kg). This dose of radioimmunotherapy was feasible when patients with altered biodistribution of In2B8 were excluded, and it was highly effective. (Cancer Sci 2005; 96: 903-910).

Adult↗

PubMed2005

Absence of strand bias for deletion mutagenesis during chromosomal leading and lagging strand replication in Escherichia coli.

Investigations were carried out to determine whether both DNA strands involved in Escherichia coli chromosomal DNA replication are replicated with similar accuracy. Experiments consisted of measuring the forward mutation rate from tonB(+) to tonB(-) in pairs of polA deficient strains in which the chromosomal target gene tonB was oriented in the two possible directions relative to the origin of replication, oriC. Within these pairs, the tonB sequence would be subjected to leading strand replication in one orientation and to lagging strand replication in the other. The most common tonB mutations in the polA1 strain were deletions followed by frameshifts. Among the deletions, a strong hotspot site with a 13-base deletion in the polA1 strains accounted for 18 of the 33 deletions in the one orientation, and 31 of the 58 deletions in the other. The results suggested that the two strands were replicated with equal or similar accuracy for deletion formation.

DNA Polymerase I↗

PubMed2005

Establishing reference values for both total soluble Fms-like tyrosine kinase 1 and free placental growth factor in pregnant women.

It has been reported that the concentration of free placental growth factor (PIGF) is decreased and that of soluble fms-like tyrosine kinase 1 (sFlt-1) is increased before the onset of preeclampsia. However, no study has determined the reference values for sFlt-1 and free PIGF during pregnancy using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. This longitudinal cohort study was undertaken to address this issue. Serum samples were collected from 148 women at 10, 18, 28, and 37 weeks of gestation. Preeclampsia occurred in 6 women: 4 women who delivered at <37 weeks of gestation, and 2 women who delivered at > or =37 weeks. The average and 90% confidence interval (90% CI) of the serum concentration of both sFIt-1 and free PIGF were determined in a total of 433 specimens from 148 subjects with 1 to 4 collections at 7 to 39 weeks of gestation, and were represented as quadric curves. The mean values (90% CI) of sFlt-1 (pg/ml) at 10, 18, 28, and 37 weeks of gestation were 413 (174-981), 296 (125-704), 413 (174-982), and 1,130 (477-2,690), respectively. The mean values (90% CI) of free PIGF (pg/ml) were 36 (14-89), 206 (83-515), 518 (207-1,290), and 354 (142-884), respectively. We also established the reference values for the ratio of sFlt-1/PIGF. These values may be useful for predicting the subsequent occurrence of preeclampsia.

Adult↗

PubMed2005

The application of molecular analyses for primary granulocytic sarcoma with a specific chromosomal translocation.

Primary granulocytic sarcoma (GS) is a rare disease defined by the absence of antecedent or concomitant leukemic cells in the bone marrow and the peripheral blood. Immunohistochemical staining for myeloperoxidase is necessary for a definite diagnosis. Otherwise, primary GS is often misdiagnosed as a malignant lymphoma or other malignancies. Primary GS is well known to frequently develop into acute myeloid leukemia (AML). Here we describe a 28-year-old woman with primary GS manifesting as an epidural tumor in the sacral region accompanied by meningeal dissemination. Fluorescence in situ hybridization analysis detected the AML1/MTG8 fusion gene in neoplastic cells obtained from her cerebrospinal fluid specimen and the epidural mass. The AML1/MTG8 fusion gene transcript was also detected by a nested reverse transcriptase-polymerase chain reaction analysis of mononuclear cells from the bone marrow, although leukemic cells were not recognized in a microscopical examination of the patient's bone marrow. Systemic chemotherapy with high-dose cytarabine followed by local radiotherapy was performed, and the patient clinically achieved a complete response. These molecular analyses provide a precise method of diagnosis, especially with respect to the French-American-British AML classification, according to the characteristic karyotypic alterations, and a patient consequently can quickly be given appropriate systemic chemotherapy as induction therapy.

Adult↗

PubMed2005

C-terminus of p47(phox) is required for interaction with leukocyte type rat 12-lipoxygenase.

In yeast two-hybrid system, rat 12-lipoxygenase (12-LO) bound to complete (390 amino acids) or the N-terminus truncated form of human p47 (phox), but not to the C-terminus truncated form (residues 1-286). When glutathione S-transferase fused human p47(phox) was added to an in vitro 12-LO enzyme activity assay, formation of 12-hydroperoxyeicosatetraenoic acid was reduced significantly compared to the C-terminus truncated form. These results indicate that C-terminus of p47(phox) is important for its interaction to rat 12-LO.

Animals↗

PubMed2005

Effect of granulocyte colony-stimulating factor on opsonin receptor expression in cerulein-induced acute pancreatitis.

OBJECTIVES: Decreased levels of expression of opsonin receptors (CD11b and CD32/16) on peritoneal exudate neutrophils may lead to susceptibility to infection. Granulocyte colony-stimulating factor (G-CSF) increases the expression levels of CD11b on neutrophils and prolongs neutrophil survival. The effects of G-CSF on neutrophils and opsonin receptor expressions of neutrophils were investigated in cerulein-induced acute pancreatitis. METHODS: Forty-two mice were randomly assigned to each group (n = 6). Mice received subcutaneous G-CSF (120 microg/kg body weight) before the induction of acute pancreatitis with cerulein. Saline was used for instead of G-CSF or cerulein solution in control groups. CD11b and CD32/16 expression levels on circulatory and peritoneal exudate neutrophils were investigated 6 and 24 hours after the induction of acute pancreatitis. RESULTS: Treatment with G-CSF did not aggravate the inflammation of pancreatic tissue evaluated by plasma amylase, acinar necrosis. However, it significantly increased the number of peritoneal exudate neutrophils (P < 0.05) and the CD11b- (P < 0.05) and CD32/16-positive (P < 0.05) peritoneal exudate neutrophils in mice with cerulein-induced acute pancreatitis. The means of fluorescence intensity for CD11b and CD32/16 expressions on circulatory and peritoneal exudate neutrophils were also elevated in the G-CSF groups. CONCLUSION: G-CSF administration increases the numbers of neutrophils and improves expression levels of opsonin receptors on neutrophils in mice with cerulein-induced acute pancreatitis.

Acute Disease↗

PubMed2005

Diffuse large B-cell lymphoma with extra Bcl-2 gene signals detected by FISH analysis is associated with a "non-germinal center phenotype".

Amplification and translocation of the Bcl-2 gene has been detected in a certain subset of diffuse large B-cell lymphomas (DLBCL). The correlations among Bcl-2 protein expression, gene translocation or amplification, and the molecular signature determined by cDNA array are poorly understood. This study examined 25 cases with de novo nodal DLBCL. Interphase fluorescence in situ hybridization (FISH) analysis was performed to evaluate the Bcl-2 gene using IGH/BCL2 and CEP18 centromere probes (Vysis). When extra Bcl-2 gene signals were observed in each tumor cell and when these signals were in proportion to the extra CEP18 probe signals, we regarded the findings as indicating the presence of an additional chromosome 18; when extra Bcl-2 signals were observed but additional CEP18 signals were not, we regarded the findings as indicating the presence of gene amplification. A panel of 3 antigens (CD10, Bcl-6, and MUM-1) was applied to categorize each case as either a "germinal center B-cell (GCB) phenotype" or a "non-GCB phenotype." Of the 25 cases examined, 8 cases (32%) were classified as "GCB phenotype" and 17 cases (68%) were classified as "non-GCB phenotype." A FISH analysis revealed that t(14;18) was detected in 2 of the 8 cases (25%) with the "GCB phenotype" but in none of the 17 "non-GCB phenotype" cases. Extra Bcl-2 gene signals were detected in 7 of the 25 (28%) cases examined: n = 5 for an additional chromosome 18, n = 1 for gene amplification, and n = 1 for additional chromosome 18 + gene amplification. Extra Bcl-2 gene signals were exclusively detected in DLBCL with the "non-GCB phenotype"; these cases, with the exception of one, stained strongly positive for Bcl-2. The DLBCLs with Bcl-2 protein overexpression were classified into at least two heterogeneous molecular groups, based on the results of the FISH analysis.

Adult↗

PubMed2005

[JCCLS phlebotomy standards].

In 2004, the Japanese Committee of Clinical Laboratory Standards (JCCLS) published a standard phlebotomy guideline, which not only ensures the safety of the patients and phlebotomists but is adopted to the healthcare setting in Japan. This phlebotomy standard is also essential for the standardization of clinical laboratory tests. This guideline was completed on the basis of current phlebotomy procedures widely in use in Japan using phlebotomy standards in the USA as references, while reconsidering their scientific reasoning as far as possible. At the same time, factors such as practicality and cost benefit were taken into account. The content of the guideline includes necessary facilities and equipment, a step by step safe but practical venipuncture procedure, an explanation of the individual steps, and other supplementary information such as alternative methods. The first edition, published as tentative guideline, is planned to be revised after a set period of time based on the comments and suggestions from a wide range of people concerned, so that it can be published as an approved guideline.

Clinical Laboratory Techniques↗

PubMed2005

Roles of IQGAP1 in cell polarization and migration.

Cell polarization and migration are fundamental processes in all organisms and are stringently regulated during tissue development, chemotaxis and wound healing. Migrating cells have a polarized morphology with an asymmetric distribution of signalling molecules and the cytoskeleton. Linkage of microtubule plus ends to the cortical region is essential for polarized migration. +TIPs, including CLIP-170 and APC (adenomatous polyposis coli) are thought to function as capturing devices at specialized cortical regions. Rho family GTPases, particularly Rac1 and Cdc42, play pivotal roles in cell polarization and migration acting through their effectors. We found that IQGAP1, an effector of Rac1 and Cdc42, interacts with CLIP-170. Activated Rac1 and Cdc42 enhance the binding of IQGAP1 to CLIP-170, and capture GFP-CLIP-170 at the base of leading edges and filopodia, respectively. Recently, we found that IQGAP1 directly binds to APC in addition to CLIP-170. IQGAP1 and APC interdependently localize to leading edges in migrating cells. IQGAP1 can link APC to actin filaments in vitro. Thus, activation of Rac1 and Cdc42 in response to migration signals leads to recruitment of IQGAP1 and APC which, together with CLIP-170, form a complex that links the actin cytoskeleton and microtubule dynamics during cell polarization and migration.

Actins↗