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T Oda

Publications and source records attributed to T Oda.

At least 19 recordsLinked to original sources
PubMed2001

Prostate-specific antigen induces osteoplastic changes by an autonomous mechanism.

The high prevalence of osteoplastic bone metastasis in prostate cancer (PC) is believed to be attributable to the production of osteoblast-stimulating factors by PC cells. Prostate-specific antigen (PSA) is a serine protease and an important serological marker for PC. Exposure of osteoblasts to PSA in vitro was found to result in cell proliferation and marked upregulation of transforming growth factor-beta (TGF-beta) mRNA expression. This PSA-induced increase in osteoblast proliferation was inhibited by anti-TGF-beta antibodies and serine protease inhibitors. In vivo, PSA markedly enhanced osteoplastic changes in human adult bone implanted into NOD/SCID mice without PC cells, and alpha(1)-antichymotrypsin prevented the PSA-induced increase in bone volume. PSA promotes osteoplastic change by activating an osteoblast autonomous mechanism that is independent of the production of bone growth factors by PC cells.

Aged↗
PubMed2001

Mechanical properties of the human cervical spine as shown by three-dimensional load-displacement curves.

STUDY DESIGN: The mechanical properties of multilevel human cervical spines were investigated by applying pure rotational moments to each specimen and measuring multidirectional intervertebral motions. OBJECTIVES: To document intervertebral main and coupled motions of the cervical spine in the form of load-displacement curves. SUMMARY OF BACKGROUND DATA: Although a number of in vivo and in vitro studies have attempted to delineate normal movement patterns of the cervical spine, none has explored the complexity of the whole cervical spine as a three-dimensional structure. METHODS: Sixteen human cadaveric specimens (C0-C7) were used for this study. Pure rotational moments of flexion-extension, bilateral axial torque, and bilateral lateral bending were applied using a specially designed loading fixture. The resulting intervertebral motions were recorded using stereophotogrammetry and depicted as a series of load-displacement curves. RESULTS: The resulting load-displacement curves were found to be nonlinear, and both rotation and translation motions were coupled with main motions. With flexion-extension moment loading, the greatest degree of flexion occurred at C1-C2 (12.3 degrees), whereas the greatest degree of extension was observed at C0-C1 (20.2 degrees). With axial moment loading, rotation at C1-C2 was the largest recorded (56.7 degrees). With lateral bending moments, the average range of motion for all vertebral levels was 7.9 degrees. CONCLUSIONS: The findings of the present study are relevant to the clinical practice of examining motions of the cervical spine in three dimensions and to the understanding of spinal trauma and degenerative diseases.

Analysis of Variance↗
PubMed2001

Superior outcome of infant acute myeloid leukemia with intensive chemotherapy: results of the Japan Infant Leukemia Study Group.

This study analyzed data on 35 infants with acute myeloid leukemia (AML) who were treated with intensive chemotherapy between 1995 and 1998 in Japan. The incidence of boys, younger age (< 6 months old), and hyperleukocytosis at onset was high in patients with the M4/M5 subtype (n = 23) in the French-American-British classification, compared with the non-M4/M5 subtype (n = 12). Thirteen (56%) and 16 (70%) patients with the M4/M5 subtype also showed 11q23 translocations and MLL gene rearrangements, respectively, whereas only one patient with the non-M4/M5 subtype had this rearrangement. All 35 patients were treated with the ANLL91 protocol consisting of etoposide, high-dose cytarabine, and anthracyclines. Overall survival and the event-free survival (EFS) rates at 3 years of all patients were 76% (95% confidence interval [CI], 61.3%-90.7%) and 72% (95% CI, 56.4%-87.9%), respectively. EFS showed no significant difference between 2 subgroups divided by age, gender, presence of the MLL gene rearrangements, and white blood cell count at onset; EFS in patients with the M4/M5 subtype tended to be better than those with the non-M4/M5 subtype. Although all 6 patients who underwent allogeneic stem cell transplantation (SCT) have been in complete remission, no benefit of SCT was confirmed. These findings suggest that the intensive chemotherapy with the ANLL91 protocol might have been responsible for the observed good outcome of infant AML, even without SCT. The presence of the MLL gene rearrangements or the age at onset had no impact on the outcome of infant AML.

Aclarubicin↗
PubMed2001

A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA.

Fanconi anemia (FA) is an autosomal recessive disease with congenital anomalies, bone marrow failure, and susceptibility to leukemia. Patient cells show chromosome instability and hypersensitivity to DNA cross-linking agents. At least 8 complementation groups (A-G) have been identified and 6 FA genes (for subtypes A, C, D2, E, F, and G) have been cloned. Increasing evidence indicates that a protein complex assembly of multiple FA proteins, including FANCA and FANCG, plays a crucial role in the FA pathway. Previously, it was reported that FANCA was phosphorylated in lymphoblasts from normal controls, whereas the phosphorylation was defective in those derived from patients with FA of multiple complementation groups. The present study examined phosphorylation of FANCA ectopically expressed in FANCA(-) cells. Several patient-derived mutations abrogated in vivo phosphorylation of FANCA in this system, suggesting that FANCA phosphorylation is associated with its function. In vitro phosphorylation studies indicated that a physiologic protein kinase for FANCA (FANCA-PK) forms a complex with the substrate. Furthermore, at least a part of FANCA-PK as well as phosphorylated FANCA were included in the FANCA/FANCG complex. Thus, FANCA-PK appears to be another component of the FA protein complex and may regulate function of FANCA. FANCA-PK was characterized as a cytoplasmic serine kinase sensitive to wortmannin. Identification of the protein kinase is expected to elucidate regulatory mechanisms that control the FA pathway.

Androstadienes↗
PubMed2001

HSH2: a novel SH2 domain-containing adapter protein involved in tyrosine kinase signaling in hematopoietic cells.

We isolated a cDNA clone encoding a novel Src homology (SH)2 domain-containing protein of 47 kDa from a human cDNA library. As its transcript was predominantly expressed in hematopoietic cells, this gene was termed HSH2 for hematopoietic SH2 protein. This protein contains several putative protein-binding motifs, SH3-binding proline-rich regions, and phosphotyrosine sites, but lacks enzymatic motifs. In a yeast two-hybrid screen, we identified a cytokine-regulated tyrosine kinase c-FES and an activated Cdc42-associated tyrosine kinase ACK1 as HSH2 interactors. HSH2 bound c-FES via its C-terminal region as well as its N-terminal region including the SH2 domain, whereas it bound ACK1 via its N-terminal proline-rich region. Furthermore, these two kinases bound and tyrosine-phosphorylated HSH2 in mammalian cells. Hence, we postulate that HSH2 functions as an adapter protein involved in tyrosine kinase signaling, and possibly regulates cytokine signaling and cytoskeletal reorganization, in hematopoietic cells.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Involvement of CCAAT/enhancer-binding protein in regulation of the rat serine:pyruvate/alanine:glyoxylate aminotransferase gene expression.

In the rat liver, transcription of the serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT) gene occurs from two sites, +1 and +66, in exon 1, resulting in the formation of two mRNAs, one for a precursor of mitochondrial SPT/AGT and the other for peroxisomal SPT/AGT, respectively. In this study, we attempted to characterize the downstream promoter responsible for generation of peroxisomal SPT/AGT. The minimal downstream promoter was confined to the +21-+90 region. We demonstrated that C/EBPalpha and C/EBPbeta bound around the downstream start site (+66) contribute to the promoter activity. The downstream promoter activity is also regulated positively by a short inverted repeat, located 20-30 bp upstream of the downstream start site, through a protein factor(s) bound to this region. On the other hand, the sequence just downstream of the start site may negatively regulate the promoter activity.

Animals↗
PubMed2001

Pedicle screw adjustments affect stability of thoracolumbar burst fracture.

STUDY DESIGN: An in vitro biomechanical study of the stabilizing effect of pedicle screw instrumentation on experimental thoracolumbar burst fractures. OBJECTIVES: To evaluate the effects of different adjustments applied by the pedicle screw fixation device on the stability of the spine-device construct. SUMMARY OF BACKGROUND DATA: Pedicle screw devices are widely used to accomplish spinal reduction and provide stability to an injured spine. In previous biomechanical studies the stability of the spine-device constructs has been examined for many devices. However, no study has quantitatively assessed the associations between the device adjustments and the stability of the construct. METHODS: Five-vertebrae human cadaveric specimens with burst fracture at L1 vertebra were studied. Pedicle screw fixation device was attached to the T12 and L2 vertebrae. Five device adjustments (pure compression, pure distraction, pure extension, a combination distraction-extension, and neutral posture) were studied. Multidirectional flexibility test was performed when intact, after burst fracture, and after each device adjustment to document spinal stability. RESULTS: The construct stability had a complex association to the device adjustment. For example, the maximum flexion and extension stabilities were achieved by pure compression and distraction-extension combination adjustments, respectively. Pure distraction and pure extension adjustments decreased the construct stability. CONCLUSIONS: The device adjustments affected the spinal construct stability differently in different directions. Although pure compression provided the most stability in most directions, the combined distraction-extension adjustment may be more suitable considering the neural decompression also.

Adult↗
PubMed2001

Accumulation of losses of heterozygosity and multistep carcinogenesis in pulmonary adenocarcinoma.

Sixty-six replacing growth-type early lung adenocarcinomas, measuring 2 cm or less across their greatest dimension, were used to investigate allelic losses at eight loci on the eight chromosomes carrying the principal cancer-associated genes. In total, 2 (16.7%) of 12 type A tumors (localized bronchioloalveolar carcinoma, LBAC) and 11 (39.3%) of 28 type B tumors (LBAC with alveolar collapse), which correspond to early lung adenocarcinomas including cancers in situ, showed allelic losses in one or more of the regions examined. In contrast, 25 (96.2%) of 26 type C tumors (LBAC with active fibroblastic proliferation), which correspond to small but advanced tumors, showed allelic losses in one or more regions. The change in histology from type A to type C was characterized by a significant rise in the incidence of allelic losses (P < 0.01). Deletions of 3p, 17p, 18q, and 22q increased significantly during malignant progression. In type C tumors that showed heterogeneous histological features, the tumor cells in the central fibrotic areas exhibited more allelic losses than those in the peripheral bronchioloalveolar growths and were, therefore, considered to have progressed to a more advanced stage than the tumor cells in the peripheral regions.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Novel kinetic analysis of enzymatic dipeptide synthesis: effect of pH and substrates on thermolysin catalysis.

The point of maximum activity is specific to a particular substrate-enzyme system but may vary with different substrates and the same enzyme. The specificity of enzymes has, however, been generally reported only at their "optimal" pH. In this article, we introduce the Michaelis-Menten equation taking pH into account, and apply it to the pH-activity profile of the thermolysin-catalyzed dipeptide synthesis. It has been reported to date that the pH-activity profile of thermolysin follows a bell-shaped curve with a maximal activity at or near pH 7.0. The profiles obtained in this study, however, indicated that the optimal pH varied from 5.8 (for F-AspPheOMe) to 7.3 (for Z-ArgPheOMe), and the order of thermolysin activity was greatly dependent on the pH of reaction media. We have succeeded in evaluating the substrates-induced change of the dissociation states of the active site of thermolysin using the hydrophobicity of substrates. We have obtained apparent kinetic parameters which are independent of the pH of reaction media. The apparent specificity of thermolysin which were independent of pH of the reaction media was in order L-Leu > L-Asp > L-Arg > L-Ala > L-Gly > L-Val and Z > Boc = F at P1 and P2 positions, respectively.

Amino Acids↗
PubMed2001

Transcriptionally active HERV-K genes: identification, isolation, and chromosomal mapping.

Preceding the isolation of transcriptionally active HERV-K genes, expression status was examined by RT-PCR and sequence analysis of mRNA from various tissues. In addition to the detection of IDDMK(1,2)22/HERV-K18 expression in peripheral leukocytes, three novel members of the family, which are expressed in multiple tissues, were identified. The novel HERV-K genes (HGMW-approved symbols ERVK4 and ERVK5) were isolated from a BAC library using oligonucleotide probes and assigned by RH mapping to chromosomal regions 3q21-q25.2, 3cen-q13, and 1q21-q23. Although their expression could not be confirmed in any normal tissues by Northern blot analysis, substantial promoter activity of their 5' LTRs was demonstrated in luciferase assays using teratocarcinoma cell lines. Thus, they seem to have the potential to be actively transcribed. The results, combined with those of the expression analysis by RT-PCR and subsequent sequencing of cloned products, also suggest that LTR sequences with subtle base changes might play a role in gene regulation, such as tissue specificity of HERV-K expression.

Autoimmune Diseases↗
PubMed2001

Corticobasal degeneration presenting with nonfluent primary progressive aphasia: a clinicopathological study.

A 62-year-old woman initially presented with slowly progressive nonfluent aphasia with minimal intellectual involvement. Echolalia and personality change were prominent whereas parkinsonian features and signs suggesting parietal lobe dysfunctions were not present. The patient's language deficit was consistent with transcortical motor aphasia. She did not manifest extrapyramidal signs. The patient was diagnosed as having Pick's disease or frontal lobe dementia. She died at age 65, 2 years and 9 months following disease onset. Neuropathological findings including cytoskeletal abnormalities, however, were clearly distinct from those of classical Pick's disease and were consistent with those reported in corticobasal degeneration (CBD). The distribution of her cortical lesions was accentuated in the frontal language-related area. The clinical manifestations in CBD are diverse, and primary progressive nonfluent aphasia should be considered as an initial symptom of CBD. Neuropathological examination of such patients should include cytoskeletal abnormality studies.

Aphasia, Primary Progressive↗
PubMed2001

Portal vein thrombosis successfully treated with a colectomy in active ulcerative colitis: report of a case.

Portal vein thrombosis is a rare complication in ulcerative colitis. We present a patient with portal vein thrombosis in ulcerative colitis who was successfully treated with colectomy. A 38-year-old Japanese female was admitted to our hospital because of an exacerbation of colitis. Abdominal ultrasonography performed because of liver dysfunction showed the thrombus in an umbilical portion of the portal vein. The patient underwent a subtotal colectomy and ileostomy because her colitis did not respond to intensive intravenous therapy. Although portal vein thrombus was treated with an intravenous infusion of urokinase before the operation, no change in the thrombus size was found. Approximately three months after the colectomy, the thrombus of the portal vein disappeared without anticoagulant therapy. Although a resection of an inflamed colon may be theoretically effective in the thrombosis in the inflammatory bowel disease, its benefit has not been confirmed. Our case suggests that the resection of the diseased bowel may have a favorable effect on the course of portal vein thrombosis in acute attacks of ulcerative colitis.

Adult↗
PubMed2001

Treatment of VX2 carcinoma implanted in the liver with arterial and intraperitoneal administration of oily anticancer agents.

PURPOSE: Long-term survival and cure cannot be achieved in patients with unresectable, advanced abdominal cancer, because no chemotherapeutic treatment has definite antitumor activity for malignant solid tumor and its dissemination. In this study, arterial and intraperitoneal administration of oily anticancer agents, which have properties that permit targeted chemotherapy for VX2 carcinoma implanted in the liver, was attempted to achieve long-term survival. MATERIALS AND METHODS: Rabbits bearing VX2 tumors in the liver measuring 1-2 cm in diameter received an arterial injection of 0.2 ml of nitrogen mustard N-Oxide (HN2-O) dissolved in Lipiodol (7.5 mg/ml), a newly developed oily anticancer agent, for the tumor and an intraperitoneal injection of a cocktail of oily anticancer agents for the prevention of intraperitoneal dissemination. RESULTS: Twelve out of thirteen rabbits survived and VX2 cancer was not observed in these 12 rabbits. The controls received a sham operation, an intraperitoneal injection of the cocktail of oily anticancer agents alone, or an arterial injection of HN2-O/Lipiodol alone. In these control groups, 27 out of 29 rabbits died of cancer. To examine the dose form for arterial injection, 14 rabbits received an arterial injection of the simple mixture of HN2-O dissolved in physiological saline and Lipiodol, with an additional intraperitoneal injection of the cocktail. Eight of these 14 rabbits died of enlargement of the hepatic tumor and peritoneal dissemination. CONCLUSION: Long-term survival and cure was achieved in almost all rabbits bearing VX2 tumor in the liver by simultaneous arterial and intraperitoneal injection of oily anticancer agents.

Animals↗
PubMed2001

The effects of pedicle screw adjustments on the anatomical reduction of thoracolumbar burst fractures.

The short segmental pedicle screw device is widely used for the decompression of neural elements and reduction of normal anatomy. Many biomechanical studies concerning proper decompression are available. However, no study has determined the optimal device adjustment for reduction of the burst fracture to the normal anatomy. In this study, cadaveric thoracolumbar spine specimens (T11-L3) with L1 burst fractures were studied. A pedicle screw device was attached to the pedicles of the T12 and L2 vertebrae. Spinal postural changes were determined due to a set of eight clinically relevant adjustments of the device. The adjustments were combinations of axial translation (distraction/compression) and extension. The adjustments caused varying changes in spinal posture. The sequence of applying the translation and extension had no effect on the spinal posture changes. The adjustment combining 5 mm distraction with 6 degrees extension brought the burst fracture closest to the intact state, compared to all other adjustments. With this adjustment, on average the spine became 0.9 mm compressed and 2.0 degrees lordotic, compared to the intact. The results of the study show that the device adjustments of axial translation and sagittal angulation can be applied in any sequence, with the same results. The combination of 5 mm distraction with 6 degrees extension was the device adjustment that produced the closest anatomical reduction.

Adult↗
PubMed2001

Search for active endogenous retroviruses: identification and characterization of a HERV-E gene that is expressed in the pancreas and thyroid.

To elucidate possible physiological functions of human endogenous retroviruses (HERVs) and their role in the pathogenesis of human diseases, we have developed a strategy to identify transcriptionally active HERV genes. By this approach, we have identified and isolated an active HERV-E gene that was mapped to 17q11. Although the gene was predicted to produce no intact viral particles due to the presence of stop codons, long open reading frames were retained in each gag and pol region. Northern blot analyses revealed in the pancreas (and thyroid) two major transcripts, 3.3 and 4.1 kb in size, associated with 500- to 600-nucleotide-longer minor bands. Preferential expression in pancreas and thyroid gland tissues may suggest a role for this gene in physiological functions common to these tissues.

Base Sequence↗
PubMed2001

Distinct structural changes detected by X-ray fiber diffraction in stabilization of F-actin by lowering pH and increasing ionic strength.

Lowering pH or raising salt concentration stabilizes the F-actin structure by increasing the free energy change associated with its polymerization. To understand the F-actin stabilization mechanism, we studied the effect of pH, salt concentration, and cation species on the F-actin structure. X-ray fiber diffraction patterns recorded from highly ordered F-actin sols at high density enabled us to detect minute changes of diffraction intensities and to precisely determine the helical parameters. F-actin in a solution containing 30 mM NaCl at pH 8 was taken as the control. F-actin at pH 8, 30 to 90 mM NaCl or 30 mM KCl showed a helical symmetry of 2.161 subunits per turn of the 1-start helix (12.968 subunits/6 turns). Lowering pH from 8 to 6 or replacing NaCl by LiCl altered the helical symmetry to 2.159 subunits per turn (12.952/6). The diffraction intensity associated with the 27-A meridional layer-line increased as the pH decreased but decreased as the NaCl concentration increased. None of the solvent conditions tested gave rise to significant changes in the pitch of the left-handed 1-start helix (approximately 59.8 A). The present results indicate that the two factors that stabilize F-actin, relatively low pH and high salt concentration, have distinct effects on the F-actin structure. Possible mechanisms will be discussed to understand how F-actin is stabilized under these conditions.

Actins↗
PubMed2001

Structure-effect relationship in the induction of mitotic phase-specific abnormality of centrosome integrity and multipolar spindles by steroidal estrogens and their derivatives in cultured mammalian cells.

In order to determine the structure-effect relationship in the induction of centrosome disintegrity (abnormality of gamma-tubulin signals) and multipolar spindles in a cultured fibroblast cell line V79 by steroidal estrogens, the activities of various estrogens and their derivatives were investigated. Induction of centrosome disintegrity by estrogens was specific in cells in the mitotic phase and was not observed in interphase cells. The centrosome disintegrity induced 24 h after exposure to estrogens was accompanied by the appearance of multinucleated cells, but the microtubule network was organized. The rank order of potency of estrogens in inducing mitotic phase-specific centrosome disintegrity and multipolar spindles was as follows: 2-methoxyestradiol>dihydroequilin 3-methyl ether=equilin 3-methyl ether>17alpha-estradiol>17beta-estradiol 3-methyl ether=17beta-estradiol>dihydroequilin>estrone 3-methyl ether. Equilin and estrone were not effective in causing centrosome disintegrity. These results suggest that the 17-hydroxyl group, irrespective of whether it is the sterically alpha or beta form, is necessary for estradiol and dihydroequilin to cause centrosome disintegrity and that O-methylation at the C-3 position was effective for equilin and dihydroequilin in enhancing the centrosome abnormality. 2-Methoxyestradiol was the most potent inducer of the centrosome disintegrity among the tested compounds and caused the induction of multiple signals of gamma-tubulin, including more than five signals.

Animals↗