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S Mitani

Publications and source records attributed to S Mitani.

At least 19 recordsLinked to original sources
PubMed2005

C. elegans ced-13 can promote apoptosis and is induced in response to DNA damage.

The p53 tumor suppressor promotes apoptosis in response to DNA damage. Here we describe the Caenorhabditis elegans gene ced-13, which encodes a conserved BH3-only protein. We show that ced-13 mRNA accumulates following DNA damage, and that this accumulation is dependent on an intact C. elegans cep-1/p53 gene. We demonstrate that CED-13 protein physically interacts with the antiapoptotic Bcl-2-related protein CED-9. Furthermore, overexpression of ced-13 in somatic cells leads to the death of cells that normally survive, and this death requires the core apoptotic pathway of C. elegans. Recent studies have implicated two BH3-only proteins, Noxa and PUMA, in p53-induced apoptosis in mammals. Our studies suggest that in addition to the BH3-only protein EGL-1, CED-13 might also promote apoptosis in the C. elegans germ line in response to p53 activation. We propose that an evolutionarily conserved pathway exists in which p53 promotes cell death by inducing expression of two BH3-only genes.

Amino Acid Sequence↗
PubMed2004

A new scoring system for Perthes' disease based on combined lateral and posterior pillar classifications.

We have devised a combined pillar score (CPS) system, based on the lateral pillar (LP) and the posterior pillar (PP) classifications, together with the age at onset of Perthes' disease, and examined its correlation with prognosis. The correlation coefficient of the Catterall classification, LP, PP, and CPS systems with the Stulberg system was 0.39, 0.52, 0.50, and 0.70, respectively. Overall 21 of the 22 hips (95.4%) with a CPS of 0 to 1 point had a good outcome and 12 of the 13 hips (92.3%) with a CPS of 3 points or more had a fair or poor outcome. None with a CPS of 2 points, had a poor outcome. The study shows that an accurate prediction of the prognosis is not possible with the LP classification alone for patients classified as belonging to group B (LP height 50% to 100% of contralateral height). The CPS system does allow accurate prediction of outcome.

Age of Onset↗
PubMed2003

Laser excitation of high-frequency capillary waves.

The laser-induced surface deformation (LISD) technique was applied to generate high-frequency capillary waves on liquid surfaces up to several tens of kHz in a noncontact manner. The dynamic response of the fluid near the surface was theoretically derived under the condition of periodical radiation pressure. The result of the numerical calculation predicts the propagation of induced capillary waves out from the excitation region. The efficiency of the wave generation was experimentally examined by changing the width of the excitation laser beam at the surface. The observed LISD spectra were well reproduced by the theory, showing that the effective frequency band can be extended up to over 100 kHz. The propagation of the optically generated wave was measured with a laser probe sweeping the position of the observation. The spatial profile gives the surface tension and the shear viscosity of the sample liquid. The frequency domain measurement was also carried out and the spectrum obtained at a fixed point agrees with the theory, demonstrating the rapid measurement of frequency-dependent phenomena.

Journal Article↗
PubMed2002

Expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) during fracture healing.

Localization and expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) during fracture healing in mouse ribs were investigated. In situ hybridization demonstrated that CTGF/Hcs24 mRNA was remarkably expressed, especially in hypertrophic chondrocytes and proliferating chondrocytes, in the regions of regenerating cartilage on days 8 and 14 after fracture. CTGF/Hcs24 mRNA was also expressed in proliferating periosteal cells in the vicinity of the fracture sites on days 2 and 8, and in cells in fibrous tissue around the callus on day 8. Northern blot analysis showed that expression of CTGF/Hcs24 mRNA was 3.9 times higher on day 2 of fracture healing than that on day 0. On day 8, it reached a peak of 8.6 times higher than that on day 0. It then declined to a lower level. Immunostaining showed that CTGF/Hcs24 was localized in hypertrophic chondrocytes and proliferating chondrocytes in the regions of regenerating cartilage, and in active osteoblasts in the regions of intramembranous ossification. Although CTGF/Hcs24 was abundant in the proliferating and differentiating cells (on days 8 and 14), immunostaining decreased as the cells differentiated to form bone (on day 20). CTGF/Hcs24 was also detected in cells in fibrous tissue, vascular endothelial cells in the callus, and periosteal cells around the fracture sites. These results suggest that CTGF/Hcs24 plays some role in fracture healing.

Animals↗
PubMed2001

C. elegans slit acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/Robo receptor.

Robo receptors interact with ligands of the Slit family. The nematode C. elegans has one Robo receptor (SAX-3) and one Slit protein (SLT-1), which direct ventral axon guidance and guidance at the midline. In larvae, slt-1 expression in dorsal muscles repels axons to promote ventral guidance. SLT-1 acts through the SAX-3 receptor, in parallel with the ventral attractant UNC-6 (Netrin). Removing both UNC-6 and SLT-1 eliminates all ventral guidance information for some axons, revealing an underlying longitudinal guidance pathway. In the embryo, slt-1 is expressed at high levels in anterior epidermis. Embryonic expression of SLT-1 provides anterior-posterior guidance information to migrating CAN neurons. Surprisingly, slt-1 mutants do not exhibit the nerve ring and epithelial defects of sax-3 mutants, suggesting that SAX-3 has both Slit-dependent and Slit-independent functions in development.

Animals↗
PubMed2001

Diagnosis of infection after total hip arthroplasty.

Forty-eight total hip arthroplasties for which revision surgery was performed were reviewed to determine the accuracy of laboratory tests, plain radiographs, hip aspiration, and technetium-99m MDP and gallium-67 scans in demonstrating the presence or absence of infection of the prosthesis. Six of the 48 hips were diagnosed as having an infection at the revision surgery. The erythrocyte sedimentation rate and the C-reactive protein levels were significantly higher in the patients with infected prostheses. The difference in the white blood cell count was not significant. There was no significant relationship between the presence of infection and the severity of loosening and instability of the implants diagnosed by plain radiographs. The accuracy of hip aspiration in diagnosing the infection was 83%, with a sensitivity of 40% and a specificity of 92%. The accuracy of technetium-99m MDP bone scan was 79%, with a sensitivity of 83%, and a specificity of 79%. Gallium-67 scan had an accuracy of 96%, a sensitivity of 67%, and a specificity of 100%. The findings in the present study indicated that diagnostic tests consisting of laboratory tests and plain radiography, followed by hip aspiration and sequential use of technetium-99m MDP and gallium-67 scintigraphies, are suitable for differentiation between mechanical loosening and infection of total hip arthroplasty.

Aged↗
PubMed2001

Analysis of c-myc DNA amplification in non-small cell lung carcinoma in comparison with small cell lung carcinoma using polymerase chain reaction.

Previous studies of c-mvc DNA amplification in lung cancer have focused primarily on analysis of small cell carcinoma or its tumor cell lines. There are few data about c-myc DNA amplification in histological types of lung cancer other than small cell carcinoma. Therefore the present study was conducted to investigate c-myc oncogene amplification in non-small cell lung carcinoma. We studied 46 lung tumor specimens for c-myc DNA amplification (15 adenocarcinomas, 15 squamous cell carcinomas, 6 large cell carcinomas, and 10 small cell carcinomas). Polymerase chain reaction, digoxigenin DNA labeling, and electrophoresis were utilized to investigate the c-myc copy number in the lung tumor specimens. The c-myc copy number of non-small cell carcinoma ranged from 1.5 to more than 20.0 in adenocarcinoma and squamous cell carcinoma, and from 6.0 to 12.0 in large cell carcinoma. That of small cell carcinoma ranged from 1.8 to 12.0. The c-myc copy number of non-small cell carcinoma was significantly higher than that of small cell carcinoma (Wilcoxon rank sum test, Z=2.06 P=0.040). However, the differences in c-myc copy number among these four histological types were not statistically significant. Amplification of c-myc (more than 4 copies) was observed not only in small cell carcinoma but also in nonsmall cell carcinoma at similarly high frequency (12/15 in adenocarcinoma and squamous cell carcinoma, 6/6 in large cell carcinoma, and 9/10 in small cell carcinoma).

Adenocarcinoma↗
PubMed2000

Characterization of mutations induced by ethyl methanesulfonate, UV, and trimethylpsoralen in the nematode Caenorhabditis elegans.

The genome project of the nematode Caenorhabditis elegans is completed. It is important and useful to disrupt nematode genes to know their function. We treated wild-type animals with potential candidates for mutagens for reverse genetics, EMS (ethyl methanesulfonate), short-wavelength UV, and long-wavelength UV in the presence of TMP (trimethylpsoralen). We estimated forward mutation rates by counting the occurrence of a marker unc-22 mutation. We found that the forward mutation rate by TMP/UV could be comparable with EMS by improving the frequency one order higher than before. We next isolated mutants of another marker gene ben-1 and examined the probability for the deletion mutations by PCR and sequencing. Deletion mutations were found only by TMP/UV method, which suggested TMP/UV is the choice for deletion mutagenesis among these methods. As a pilot experiment, we could isolate actual deletion mutations at a much higher frequency than previously.

Animals↗
PubMed2000

Structure and expression pattern of a human MTG8/ETO family gene, MTGR1.

AML1-MTG8 fusion protein, which is produced from the rearranged gene formed between AML1 and MTG8 in myeloid leukemia with t(8;21) chromosomal translocation, plays an important role in the pathogenesis of leukemia. We previously showed that ectopically expressed AML1-MTG8 fusion protein is associated with an MTG8-like protein in the mouse myeloid precursor cell line L-G, and this association seemed to be required for AML1-MTG8 to stimulate proliferation. As a candidate cDNA for this MTG8-like protein, a 6.4 kb MTGR1 cDNA encoding human MTGR1b protein of 604 amino acids was isolated. Since this cDNA was shorter than the main mRNA (about 7.5 kb), the 5'-end of the MTGR1 cDNA was extended using Marathon Ready cDNA. When the newly obtained 5'-sequence was combined with the previous cDNA, the resultant MTGR1 cDNA (6995 bp), including exon 3 that the previous cDNA lacked, could encode MTGR1a protein of 575 amino acids. Transcripts of the MTGR1 gene were expressed ubiquitously in the human tissues and cell lines examined. PCR analyses of the cDNAs from human tissues showed the presence of various splicing variants with regard to the 5'-region including exons 1, 2 and 3. The MTGR1 gene consists of 14 exons and spans about 68 kb. The genomic structure of MTGR1 is highly similar to those of other MTG 8-family genes, MTG8 and MTG16. MTG16 was recently cloned from the translocation breakpoint of myeloid malignancies with t(16;21) chromosomal translocation.

Alternative Splicing↗
PubMed2000

Insulin alters cardiac muscle creatine kinase activity.

The expression of mRNAs of creatine kinase (CK)-B and CK-M has been show to be affected by insulin, and myocardial CK-MB activity is suppressed in insulin-deficient rats. We investigated the dose-related effect of insulin on CK-MB activity in cardiac and skeletal muscles. Male Wistar rats were divided into three groups: (1) control group, (2) diabetic group, injected with 65 mg/kg streptozotocin for 4 weeks, and (3) atenolol group, administered 30 mg/kg per day atenolol. Each group was further divided into three subgroups and administered either saline, or 20 (Ins 20) or 30 (Ins 30) U/kg per day insulin. After 3 weeks, the isoenzyme activity of CK and lactate dehydrogenase (LDH) in the left ventricle of the heart (LV) and the major pectoral muscle (PM) was measured. Serum insulin increased and plasma glucose decreased in Ins 20 and Ins 30, dose-dependently, in all three groups. Both CK-MB and -BB activity in LV increased dose-dependently with insulin treatment in the control, diabetes, and atenolol groups, although these changes did not occur in skeletal muscles. CK-MB in LV correlated with the serum insulin levels in all rats, while no correlation was found in the skeletal muscles. These findings suggest that insulin possibly regulates the distribution of CK isoenzymes in rat heart muscle, and that the effect of insulin is not due to the sympathetic drive induced by hypoglycemia.

Adrenergic beta-Antagonists↗
PubMed2000

Predictability of the progress of secondary osteoarthritis after developmental dislocation of the hip, utilizing inferior edge (of the teardrop)--center (of the femoral head) distance.

We followed-up a group of patients in their youth and then in middle age after they had been treated for developmental dislocation of the hip, and studied whether we could predict the progress of osteoarthritis of the hip when the patients were in the "youth" stage. We studied 21 hips of 21 patients with unilateral dislocation that could be examined twice, in 1975 and 1995, in patients who were treated at our hospital between 1953 and 1963. We measured the acetabular-head index (AHI), center-edge angle (CE angle), and the Sharp angle, and our created index (inferior edge of the teardrop - center of the femoral head distance), and we divided this index by the distance of the inferior edges of the teardrops on both sides. Using these measured values, we studied whether we could predict changes in clinical and radiographic evaluation after a follow-up of 20 years. There was no significant correlation of clinical and radiographic results and AHI, CE angle, and the Sharp angle; however, there was a significant correlation with our created index. The index we created is relatively easily measured and enables us to make a more precise prognosis, in comparison with previously developed indices.

Adolescent↗
PubMed2000

Increased osteocyte apoptosis during the development of femoral head osteonecrosis in spontaneously hypertensive rats.

We investigated the presence of osteocyte apoptosis in the necrotic trabeculae of the femoral head of spontaneously hypertensive rat (SHR) using the in situ nick end labeling (TUNEL) method and transmission electron microscopy. The occurrence of osteonecrosis and ossification disturbance was significantly higher in SHR compared with Wistar Kyoto (WKY) rats, and Wistar (WT) rats used as control animals (P < 0.01). A high population of TUNEL positive osteocytes was detected mainly in 10- and 15-week-old SHRs. Sectioned examination of the femoral head of SHRs and WKY rats by electron microscopy revealed apoptotic cell appearances such as aggregation of chromatin particles and lipid formation. In contrast, a positive reaction was significantly lower in osteocytes in the femoral heads of WT rats (P < 0.01). Our results indicate that apoptosis forms an important component of the global pathologic process affecting the femoral head of SHR, which leads to osteonecrosis in this region.

Animals↗
PubMed2000

[Chronic subdural hematoma associated with malignancy: report of three cases].

Three cases of chronic subdural hematoma (CSH) associated with malignancy are reported. Case 1; A one-year-old girl was referred for vomiting and convulsions. Left CSH was removed, and her symptoms disappeared. Cytological examination of chronic subdural hematoma revealed abnormal white blood cells. A clinical diagnosis of acute monocytic leukemia was made after the laboratory examination. Remission was achieved by chemotherapy, but she died one year after the operation. Case 2; A 72-year-old woman was referred for right hemiparesis and urinary incontinence. Left CSH was irrigated, and her clinical symptoms immediately disappeared. Cytological examination of chronic subdural hematoma revealed abnormal white blood cells. A clinical diagnosis of chronic lymphocytic leukemia was made after the laboratory examination. No treatment was given since there were no clinical symptoms of chronic lymphocytic leukemia. Case 3; A 70-year-old woman who had been affected with early gastric cancer and mammary cancer for the previous two years was admitted to our clinic because of headache, right hemiparesis and consciousness disturbance. Left CSH was irrigated, and her clinical symptoms improved. However, there was a tendency to bleed because disseminated intravascular coagulation had occurred, and CT showed bilateral subdural hematoma. A second irrigation was performed, but her symptoms did not improve. Left acute subdural hematoma, which was removed by craniotomy, occurred three days after the second operation. Pathological examination of the outer membrane of the subdural hematoma revealed invasion of adenocarcinoma. She died three days after the third operation. It is recommended that both the cytological and the histological examinations be performed when possible, since they are simple to perform and very useful in some cases.

Adenocarcinoma↗
PubMed1999

Mouse ULK2, a novel member of the UNC-51-like protein kinases: unique features of functional domains.

The UNC-51 serine/threonine kinase of C. elegans plays an essential role in axonal elongation, and unc-51 mutants exhibit uncoordinated movements. We have previously identified mouse and human cDNAs encoding UNC-51-like kinase (ULK1). Here we report the identification and characterization of the second murine member of this kinase family, ULK2. Mouse ULK2 cDNA encodes a putative polypeptide of 1033 aa which has an overall 52% and 33% amino acid identity to ULK1 and UNC-51, respectively. ULKs and UNC-51 share a typical domain structure of an amino-terminal kinase domain, a central proline/serine rich (PS) domain, and a carboxy-terminal (C) domain. Northern blot analysis showed that ULK2 mRNA is widely expressed in adult tissues. In situ hybridization analysis indicated that ULK2 mRNA is ubiquitously localized in premature as well as mature neurons in developing nervous system. ULK2 gene was mapped to mouse chromosome 11B1.3 and rat chromosome 10q23 by FISH. HA-tagged ULK2 expressed in COS7 cells had an apparent molecular size of approximately 150 kDa and was autophosphorylated in vitro. Truncation mutants suggested that the autophosphorylation occurs in the PS domain. Although expression of ULK2 failed to rescue unc-51 mutant of C. elegans, a series of ULK2/UNC-51 chimeric kinases revealed that function of the kinase and PS domains are conserved among species, while the C domain acts in a species-specific manner. These results suggest that ULK2 is involved in a previously uncharacterized signaling pathway in mammalian cells.

Amino Acid Sequence↗
PubMed1999

Utility of MRI in detecting obstacles to reduction in developmental dysplasia of the hip: comparison with two-directional arthrography and correlation with intraoperative findings.

We studied the utility of magnetic resonance imaging (MRI) in detecting obstacles to reduction in developmental dysplasia of the hip (DDH) by comparing MRI findings with two-directional arthrograms and intraoperative findings. In 36 patients there were 38 DDHs; 23 complete dislocations and 15 residual subluxations. Coronal and transverse sections of T1-weighted images were used. Interpositions in the acetabulum and the anterior, superior, and posterior portions of the limbus, which were intracapsular obstacles to reduction, were evaluated. MRI and arthrography were useful for assessing the shape of the anterior portion of the limbus. In complete dislocations, MRI findings proved more valuable to detect deformities of the posterior portion of the limbus. Four of ten limbus excisions showed intermediate intensity signals on MRI. The histology was characterized by reparative granulation tissue with new capillary formation and organized thrombi. MRI proved useful for detecting obstacles to reduction, as well as for assessing morphological and histological abnormalities.

Arthrography↗