Biomedical subjects

Toshifumi Ozaki

Publications and source records attributed to Toshifumi Ozaki.

At least 19 recordsLinked to original sources

PubMed2006

Accurate diagnosis of musculoskeletal lesions by core needle biopsy.

BACKGROUND: Percutaneous needle biopsy has many advantages over open biopsy in the treatment of neoplasms. However, the accuracy of needle biopsy in the diagnosis of musculoskeletal lesions has not yet been established. Here, we evaluate the accuracy and limitations of the procedure for musculoskeletal lesions. METHODS: The diagnoses of 163 needle biopsies (bone, 91; soft tissue, 72) performed on 157 consecutive patients using a Jamshidi needle or an Ostycut needle for bone lesions, or a Tru-cut needle for soft tissue lesions were compared with the final diagnoses made by open biopsy and/or a definitive operation. RESULTS: One hundred forty-three specimens (88%) were determined to be adequate for histological examination. Obtaining undamaged cores from very hard bony lesions or sclerotic cyst walls proved difficult. A pathologist with experience in musculoskeletal lesions was able to differentiate malignant tumors from benign lesions in 97% of the cases (bone, 100%; soft tissue, 94%) and arrive at a specific diagnosis in 88% (bone, 96%; soft tissue, 78%) when adequate cores were obtained. Differentiating a well-differentiated liposarcoma from a benign lipoma and inflammatory lesions from benign tumorous conditions, was difficult. The overall accuracy was 77% (bone, 85%; soft tissue, 68%). There was no morbidity related to the procedure. CONCLUSION: The results indicate that needle biopsy is safe and accurate for diagnosing musculoskeletal lesions.

Adolescent↗

PubMed2006

Chromosomal and genetic imbalances in synovial sarcoma detected by conventional and microarray comparative genomic hybridization.

PURPOSE: To analyze the relationship between chromosomal instabilities and clinicopathological factors in synovial sarcoma (SS). METHODS: Twenty-two fresh-frozen SS were analyzed by metaphase comparative genomic hybridization (CGH). Additional microarray CGH was performed in 13 cases. RESULTS: Fourteen patients with SYT-SSX1 rearrangements and nine patients with biphasic tumor subtypes had better prognosis than the eight patients with SYT-SSX2 rearrangements and 13 patients with monophasic subtypes, respectively. Gains (average 3.0) were more frequent than losses (average 1.0). Frequent gains were identified on chromosomal regions 2, 6q, 7, 8q, 12, 17q, 18q, and 21q, whereas frequent losses were over-lapped on chromosomes 1p31-p35, 3p, 6q, 16, and 17p. High-level gains were observed on chromosomes 1q21-q31, 7, 8, 12, 17q, 18q, and 21q. Thirteen monophasic and nine biphasic tumors had an average of 5.1 and 2.8 aberrations, respectively. Patients with tumors harboring numerous aberrations (>or=3) had a worse clinical course. Microarray CGH more specifically detected genetic imbalances including gains in MDM2, MSH2, KCNK12, DCC, CDK2, ERBB3, SAS, and CDK4 and losses in HRAS, RASSF1, and CCND1. Gain of SAS was an important prognostic factor of SS. CONCLUSION: We have identified several factors influencing the prognosis of SS patients by metaphase and microarray CGH.

Adolescent↗

PubMed2006

Lateral and posterior pillar grade changes during the treatment of Perthes disease in older patients using skin traction and range of motion exercises.

INTRODUCTION: The lateral pillar (LP) grade changes detected during treatment periods have received a lot of attention recently. Lappin et al. reported LP collapses in 92 of 275 (33%) patients during the treatment, but did not provide information for comparing treatment methods and age of onset of the disease. The purpose of this study was to review radiological changes in LP grade in older patients with Perthes disease during 20 months of treatment with skin traction and ROM exercises. We have also reported any grade changes in the posterior pillar (PP) classification. MATERIAL AND METHODS: Twenty-one patients with unilateral disease who were 9 years or older at the onset of symptoms had been followed until skeletal maturity. RESULTS: Out of 21 older patients with Perthes disease, our study had two (9.5%) who experienced LP collapse and two (9.5%) who experienced PP collapse during the first 20 months of treatment. The average time from onset to hospitalization in hips, initially classified as LP group C and PP group C, was significantly longer than in LP and PP groups A and B. The LP collapse in two hips and PP collapse in two hips occurred during months 4-8 of treatment. On the other hand, of the patients allowed to ambulate with the Pogo stick orthosis from months 8 to 12 and without a brace from months 10 to 15, none had a collapse of their LPs or PPs during these periods. CONCLUSION: Lappin et al. reported that 92 of 275 patients (33%) who were managed conservatively in several hospitals experienced LP collapse during their treatment periods. Our results suggest that older patients with this disease treated with skin traction and ROM exercises rarely suffer a LP collapse, as compared with the Lappin et al. report.

Adolescent↗

PubMed2006

Diagnosis of deep vein thrombosis after operation for fracture of the proximal femur: comparative study of ultrasonography and venography.

BACKGROUND: We compared investigative methods to study the diagnostic capability of ultrasonography. Subjects were 75 patients with proximal femur fractures who underwent surgery from March 2002 to December 2003. METHODS: Biochemical assays were carried out on days 3 and 7, and D-dimer levels were investigated as a time series. Ascending lower limb venography and ultrasonography were carried out nearly simultaneously in all cases on day 7. RESULTS: The incidence of deep vein thrombosis (DVT)-positive findings on venography was 61.3% (46/75). Venography results demonstrated a diagnostic sensitivity of 95.5% and specificity of 91.4% using a D-dimer cutoff of 1microg/ml on postoperative day 7. By ultrasonography, diagnostic sensitivity for DVT was 78.3%, and specificity was 96.5%. Among all proximal area cases, there were 18 limbs with DVT seen on venography among which were 17 limbs in cases demonstrating DVT at the same site on ultrasonography, a correct diagnosis rate of 94.4%. CONCLUSIONS: For the diagnosis of a thrombus more proximal than the popliteal area, a location at high risk for occurrence of pulmonary embolism, ultrasonography provided results nearly on par with those obtained by venography. Thus, we believe that ultrasonography allowed a more noninvasive, accurate diagnosis and more rapid treatment in cases where D-dimer values were 1 microg/ml or more on postoperative day 7.

Adult↗

PubMed2006

Assessment of head wear more than ten years after total hip arthroplasty: 22-mm zirconia vs. metal heads.

The present retrospective study assessed radiographs to determine socket wear in total hip arthroplasty (THA) with 22-mm zirconia or COP (Cobalt-Chrome alloy rich in Cobalt and Phosphorous) heads, and in cemented stems at more than 10 years after operation. Sockets of ultra high molecular weight polyethylene were used in each of two THA groups (13 hips each) in a clinical trial in our hospital between 1989 and 1990. Three observers carried out masked assessments of the radiographs. Upon final examination, there was no remarkable loosening in the zirconia or COP group, and no case had required revision surgery as of 2005. There was a statistically significant difference between the 2 groups in average annual linear wear, at 0.093 mm/year and 0.046 mm/year in the zirconia and COP groups, respectively. Volume wear and average annual volume wear were also significantly greater in the zirconia group despite its superior mechanical strength and toughness in vitro. Our present findings do not confirm early expectations of lower wear in long-term results of 22-mm zirconia femoral heads used in THA.

Adult↗

PubMed2006

Expression of neurotrophins and their receptors tropomyosin-related kinases (Trk) under tension-stress during distraction osteogenesis.

The localization and expression of neurotrophins and their receptors during distraction osteogenesis was investigated in 72 male rat femurs (11 weeks old) to further clarify the concurrence of cellular and molecular events of new bone formation. After osteotomy, a 7-day lag phase was followed by distraction at the rate of 0.25 mm/12 h for 21 days (distraction phase), and a 7-day consolidation phase. The localization of neurotrophins (NGF, BDNF and NT-3) and their receptors tropomyosinrelated kinases (TRKA, TRKB and TRKC) by immunostaining showed positive staining in bone forming cells in each stage, although the presence and staining intensity varied by cell type and phase. The expressions of NGF, BDNF and NT-3 by real-time polymerase chain reaction (real-time PCR) showed that the peak of the mRNA expression of NGF occurred 10 days after distraction. NT-3 increased during bone extension, but decreased when distraction stopped. In contrast, BDNF continued to increase gradually throughout the distraction and consolidation phases. These findings suggest that neurotrophins and their receptors may play different roles in endochondral and intramembranous ossification in distraction osteogenesis. The tension stress caused by distraction may stimulate the expression of neurotrophins and their receptors, and promote osteogenesis.

Animals↗

PubMed2006

Decreased levels of insulin-like growth factor-1 and vascular endothelial growth factor relevant to the ossification disturbance in femoral heads spontaneous hypertensive rats.

Ossification disturbance in femoral head reportedly is seen in the Spontaneously Hypertensive rats (SHR) between ages of 10 and 20 weeks. We investigated serum and tissue levels of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in SHR relevant to the ossification disturbance and osteonecrosis of the femoral head. Serum levels of IGF-1 and VEGF were significantly lower in SHR than in Wistar Kyoto rats (WKY) at weeks 5, 10, 15 and 20 (p<0.005). The incidence of histological ossification disturbance of the femoral head was higher in SHR (59%) than in WKY (40%) at week 20. Lower serum and local levels of VEGF in SHR appeared to be related to the incomplete ossification of the femoral heads. Immunohistochemical study showed significantly lower numbers of IGF-1 and VEGF positive chondrocytes in the femoral epiphyseal cartilage of SHR than in those of WKY at weeks 10, 15 and 20. Our results suggest that local and/or systemic levels of IGF-1 and VEGF between ages of 5 and 20 weeks might play roles in the pathogenesis of ossifi cation disturbance of the femoral head in SHR.

Animals↗

PubMed2006

Surgical results of sacral perineural (Tarlov) cysts.

The purpose of this study was to investigate the surgical outcomes and to determine indicators of the necessity of surgical intervention. Twelve consecutive patients harboring symptomatic sacral perineural cysts were treated between 1995 and 2003. All patients were assessed for neurological deficits and pain by neurological examination. Magnetic resonance of imaging, computerized tomography, and myelography were performed to detect signs of delayed filling of the cysts. We performed a release of the valve and imbrication of the sacral cysts with laminectomies in 8 cases or recapping laminectomies in 4 cases. After surgery, symptoms improved in 10 (83%) of 12 patients, with an average follow-up of 27 months. Ten patients had sacral perineural cysts with signs of positive filling defect. Two (17%) of 12 patients experienced no significant improvement. In one of these patients, the filling defect was negative. In conclusion, a positive filling defect may become an indicator of good treatment outcomes.

Adult↗

PubMed2006

Chromosomal imbalances in malignant peripheral nerve sheath tumor detected by metaphase and microarray comparative genomic hybridization.

Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant tumors affecting adolescents and adults. There have been a few reports on chromosomal aberrations of MPNSTs; however, the tumor-specific alteration remains unknown. We characterized the genomic alterations in 8 MPNSTs and 8 schwannomas by metaphase comparative genomic hybridization (CGH). In 5 of 8 MPNSTs, microarray CGH was added for more detailed analyses. Frequent gains were identified on 3q13-26, 5p13-14, and 12q11-23 and frequent losses were at 1p31, 10p, 11q24-qter, 16, and 17. Microarray CGH revealed frequent gains of EGFR, DAB2, MSH2, KCNK12, DDX15, CDK6, and LAMA3, and losses of CDH1, GLTSCR2, EGR1, CTSB, GATA3, and SULT2A1. These genes seem to be responsible for developing MPNSTs. The concordance rate between metaphase CGH and microarray CGH was 66%. Metaphase CGH was useful for identifying chromosomal alterations before applying microarray CGH.

Adult↗

PubMed2006

Magnetic resonance angiography without contrast enhancement medium in bone and soft tissue tumors.

The aim of this study was to assess the ability of a new magnetic resonance (MR) angiography technique that does not use contrast enhancement medium to depict the vascularity of musculoskeletal neoplasms, and evaluate its clinical utility. We performed 3D fresh blood imaging (FBI) MR angiography in 57 patients with bone or soft tissue tumors, and the detection of vessels in and around the tumor was evaluated. Moreover, differences in vascularity between benign and malignant tumors were analyzed. In the lower leg, large arteries such as femoral or popliteal arteries were visible. In the trunk or arm, large vessels such as subclavian or iliac arteries were visible. Discrimination between benign and malignant tumors was impossible in bone tumors; however, the mean value of vascularity differed between benign and malignant tumors in the soft tissue tumors. This is the first trial of the FBI method for bone and soft tissue tumors. The still developing method of MRA without contrast materials could clearly depict major arteries in the trunk and the extremities, this method may replace conventional MRA of bone and soft tissue tumors because it produces vivid images while being non-invasive.

Adolescent↗

PubMed2006

Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: involvement of cyclin C in osteosarcoma.

The molecular pathogenesis of osteosarcoma is very complicated and associated with chaotic abnormalities on many chromosomal arms. We analyzed 12 cases of osteosarcomas with comparative genomic hybridization (CGH) to identify chromosomal imbalances, and detected highly frequent chromosomal alterations in chromosome 6q, 8p, 10p and 10q. To define the narrow rearranged region on chromosome 6 with higher resolution, loss of heterozygosity (LOH) analysis was performed with 21 microsatellite markers. Out of 31 cases, 23 cases (74%) showed allelic loss at least with one marker on chromosome 6q. We identified two distinct commonly deleted regions on chromosome 6 using markers D6S1565 located at 6q16 and 6q23MS1 at 6q23. The expression analysis of genes located at the deleted region was performed, and the decreased mRNA expression of the CCNC gene, one of the regulators of cell cycle, was detected. Growth of osteosarcoma cell line was significantly suppressed after the CCNC cDNA transfection. Fine mapping of the deleted region containing a possible tumor suppressor gene and the transfection assay suggest that the CCNC is a candidate tumor suppressor gene.

Cell Line, Tumor↗

PubMed2005

Blood loss and transfusion associated with musculoskeletal tumor surgery.

BACKGROUND AND OBJECTIVES: No organized data regarding the blood losses associated with musculoskeletal tumor surgery has been existed. The present study aimed to examine the extent of blood loss and the transfusion requirement associated with various kinds of musculoskeletal tumor surgeries in a large, well-defined sample. METHODS: The records of 1,047 consecutive operations for musculoskeletal tumors were reviewed. RESULTS: The total blood loss ranged from 0 to 26,050 ml (median: 95 ml). The operative time ranged from 5 to 1,140 min (median: 105 min). There was a significant correlation between the total blood loss and the operative time. The median blood loss was 10 ml in biopsies, 100 ml in curettages, 190 ml in amputations or disarticulations, 30 ml in marginal resections (bone tumors, 50 ml; soft tissue tumors, 25 ml), and 380 ml in wide resections (bone tumors, 2,155 ml; soft tissue tumors, 180 ml). Wide resections for malignant tumors were associated with significantly more blood loss than marginal resections for benign ones. Resections of bone tumors were accompanied by significantly more blood loss than those of soft tissue tumors. Overall, blood transfusions were required after 210 (20.1%) operations. CONCLUSIONS: Our results provide the first exhaustive data about blood loss and the subsequent need for transfusion associated with various kinds of musculoskeletal tumor surgeries that may be helpful for establishing a guideline for perioperative patient management.

Adolescent↗

PubMed2005

Suppression of chondrosarcoma cells by 15-deoxy-Delta 12,14-prostaglandin J2 is associated with altered expression of Bax/Bcl-xL and p21.

We previously reported that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), the most potent agonist for peroxisome proliferator-activated receptor gamma (PPAR gamma), induces apoptosis of human chondrosarcoma cell line OUMS-27. The current study aimed to explore the mechanism of 15d-PGJ(2)-induced apoptosis and inhibition of cell proliferation in OUMS-27 cells. The preliminary results of cDNA microarray analysis showed the down-regulation of anti-apoptotic Bcl-xL and up-regulation of pro-apoptotic Bax in the process of 15d-PGJ(2)-induced apoptosis. These changes were further confirmed at mRNA and protein levels by RT-PCR and Western blot analysis, respectively. Among cyclin-dependent kinase inhibitors, p21 was induced and up-regulated by 15d-PGJ(2), but p16 and p27 were not changed, suggesting that the involvement of p21 in inhibition of cell proliferation. Activation of caspase-3 by 15d-PGJ(2) was partly, but not completely, blocked by PPAR gamma antagonist (GW9662) suggesting the 15d-PGJ(2) exerted its effect by PPAR gamma-dependent and -independent pathways. Interestingly, immunohistochemical study on human chondrosarcoma samples revealed that Bcl-xL is frequently expressed by tumor cells. The results of the current study suggest that the potential ability of 15d-PGJ(2) in regulation of cell cycle and inhibition of Bcl-xL expression might be beneficial in the development of novel pharmacological agents for chondrosarcoma.

Apoptosis↗

PubMed2005

Alternating sequential chemotherapy with high-dose ifosfamide and doxorubicin/cyclophosphamide for adult non-small round cell soft tissue sarcomas.

Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.

Adult↗

PubMed2005

Posterior tibial adiposal flap for repair of wide, full-thickness defect of the Achilles tendon.

Wide, full-thickness defects on the posterior aspect of the distal lower leg involving the Achilles tendon are usually repaired with free fasciocutaneous flaps or local skin flaps. The former require microvascular techniques; there is a donor-site scar due to skin grafting; and a longer operating time. The latter results in a wide scar near the donor defect. The authors developed a new reconstructive procedure using local fascia turned over to create a new Achilles tendon, and wrapping it with a posterior tibial adiposal island flap based on the dominant perforator of the posterior tibial artery, which was elevated from the medial aspect of the lower leg. The advantages of this method are that no donor scar appeared on the posterior aspect of the lower leg, and there was no need for microvascular techniques. This method is especially suitable for young women.

Achilles Tendon↗

PubMed2005

Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats.

Traumatic spinal cord injury (SCI) results in widespread neuronal cell death. Recent studies have suggested that activated calpain mediates neuronal cell death in the central nervous system. We conducted a study to determine whether calpain mediates neuronal cell death in the motor neurons of the spinal cord after SCI, and whether postinjury administration of the calpain inhibitors N-acetyl- Leu-Leu-Met-CHO (ALLM) and calpain inhibitor III (CI III) (MDL28170) reduces the motor disturbances in rats with a model of SCI. Adult male Wistar rats were subjected to SCI by application of a 20-g weight impactor probe to the spinal cord at T12 for 20 min. The rats were divided into three groups according to whether they were injected intravenously with 0.05-2.5 mg/kg ALLM, 10 mg/kg CI III, or 0.1% DMSO as a control every 24 h for 1 week after SCI. Calpain was activated in the spinal cord at 8 h, 24 h, and 5 days after SCI, and administration of ALLM inhibited its activation. ALLM, as compared to the DMSO vehicle alone, also significantly reduced the number of motor neurons in spinal-cord lesions that were positively labeled at 24 h after SCI with the terminal deoxynucleotidyl transferase-uridine nucleotide end-labeling (TUNEL) technique. Additionally, both the inclined plane test and footprint analysis showed markedly better motor activity after 4 weeks in rats injected with ALLM or CI III than in rats given vehicle only. These results suggest that activation of calpain plays a critical role in the neuronal cell death that follows SCI, and that calpain inhibitors may have benefit in treating the motor disturbances that follow SCI.

Animals↗

PubMed2004

Significant growth suppression of synovial sarcomas by the histone deacetylase inhibitor FK228 in vitro and in vivo.

About 97% of synovial sarcomas harbor the SYT-SSX fusion gene by chromosomal translocation. We found that the histone deacetylase (HDAC) inhibitor FK228 significantly suppressed the growth of synovial sarcoma cells as compared with that of osteosarcoma. The 50% growth inhibition IC50 value we obtained for FK228 was 0.02-0.2 nM, and it indicates that its suppression effect on synovial sarcoma cells is the highest of any of the HDAC inhibitors yet reported. It was not likely that the growth suppression of FK228 depends on the doubling time of these cells. Introduction of SYT-SSX cDNA into HEK293 cells enhanced the sensitivity of the cells for FK228. Immunostaining of the FK228-treated cells using an anti-acetyl-histone H3 antibody showed that FK228 inhibits deacetylation of histone. In a mice assay, the growth of synovial sarcoma cells was markedly inhibited by FK228 treatment, and the invasion of tumors into surrounding tissues was suppressed. These results suggest that FK228 may be useful in developing therapeutic strategies to treat synovial sarcoma.

Animals↗

PubMed2004

Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A*2402 anchor substitute.

To investigate the effects of anchor substitutions in SYT-SSX junction peptide, an HLA-A24 anchor residue (position 9) of the SYT-SSX B peptide (GYDQIMPKK) was substituted to more favorable residues according to the HLA-A24-binding motif. Among four substitutes constructed, a substitute with isoleucine (termed K9I peptide) most apparently enhanced the affinity for HLA-A24 molecule. Subsequent in vitro CTL induction analysis using PBMCs of 15 HLA-A24(+) synovial sarcoma patients revealed that the original B peptide allowed to induce synovial sarcoma-specific CTLs from 7 patients (47%), whereas such CTLs were inducible from 12 patients (80%) with K9I peptide. Moreover, the extent of cytotoxicity against HLA-A24(+) synovial sarcoma cell lines was higher in K9I peptide-induced CTLs than B peptide-induced CTLs. Influence of anchor substitution on peptide/TCR interaction was evaluated by cytotoxicity assays against autologous cells and tetramer analysis. CTLs induced from a synovial sarcoma patient using K9I peptide did not lyse autologous PHA blasts or EBV-infected B cells. In vitro stimulations of PBMCs from 5 HLA-A24(+) synovial sarcoma patients with K9I peptide increased the frequency of T cells reacting with both HLA-A24/K9I peptide tetramer and HLA-A24/B peptide tetramer. In contrast, the frequency of T cells reacting with HLA/HIV-derived peptide tetramer remained low. These findings support the validity in design of anchor residue substitution in SYT-SSX fusion gene-derived peptide, and provide a potential clue to the current stagnation in vaccination trials of fusion gene-derived natural junction peptides.

Amino Acid Substitution↗