Biomedical subjects

Takashi Yanagawa

Publications and source records attributed to Takashi Yanagawa.

12 recordsLinked to original sources

PubMed2003

Regulation of cell proliferation by autocrine motility factor/phosphoglucose isomerase signaling.

Autocrine motility factor (AMF)/phosphoglucose isomerase (PGI; EC 5.3.1.9) is a housekeeping cytosolic enzyme that plays a key role in both glycolysis and gluconeogenesis pathways. AMF/PGI is also a multifunctional protein that displays cytokine properties, eliciting mitogenic, motogenic, and differentiation activities, and has been implicated in tumor progression and metastasis. Because little is known about AMF/PGI-dependent signaling in general and during tumorigenesis in particular, we sought to study its effect on the cell cycle. To elucidate the functional role of PGI, we stably transfected its cDNA into NIH/3T3 and BALB/c 3T3-A31 fibroblasts. Ectopic overexpression of PGI results in the acquisition of a transformed phenotype associated with an acceleration of G1 to S cell cycle transition. These were manifested by up-regulation of cyclin D1 expression and cyclin-dependent kinase activity and down-regulation of the cyclin-dependent kinase inhibitor p27Kip1. The reduced p27Kip1 protein expression level in PGI-overexpressing cells could be restored to control levels by treatment with proteasome inhibitor. PGI-overexpressing cells also exhibited elevated expression of Skp2 involved in p27Kip1 ubiquitination and elevation in the levels of retinoblastoma protein hyperphosphorylation. Thus, we may conclude that the overexpression of AMF/PGI enhances cell proliferation together with up-regulation of cyclin/cyclin-dependent kinase activities and down-regulation of p27Kip1, whereas the induction of 3T3 fibroblast transformation by PGI is regulated by the retinoblastoma protein pathway.

3T3 Cells↗

PubMed2003

Reconstruction with autologous pasteurized whole knee joint II: application for osteosarcoma of the proximal tibia.

Reconstruction of the knee joint for osteosarcoma of the proximal tibia is a formidable challenge. Here we present two patients whose knees were reconstructed with autologous grafts of whole-knee joint treated by extracorporeal pasteurization. Incorporation at the junction between host and pasteurized bone was evident. On the other hand, direct reattachment of the patellar tendon to the pasteurized tibia was not successful in case 1. In case 2, in contrast, the patella was divided followed by successful reconstruction at the osseous site. Avoiding reattachment of pasteurized ligamentous structure is recommended. The operation protocol is not ideal but so far may be superior to other reconstruction procedures because there are many fundamental complications such as low long-term survival of a massive prosthesis and the lethal risk of transfection (e.g. human immunodeficiency virus); moreover, immunological responses of the allograft can be avoided.

Adolescent↗

PubMed2003

FDG-PET for evaluating musculoskeletal tumors: a review.

Positron-emission tomography (PET) can provide an in vivo method for evaluating metabolism and physiology in normal and diseased tissues. Clinical trials with [(18)F]2-deoxy-2-fluoro- d-glucose (FDG), the most commonly used radiolabeled tracer for PET imaging, have demonstrated increased accumulation of FDG in several cancer tissues. In this article, we introduce the basic principles of FDG-PET and review current knowledge about FDG-PET for evaluating musculoskeletal tumors. Recent reports and our own experience suggest that FDG-PET cannot be a screening method for differential diagnosis between benign and malignant musculoskeletal lesions, including many neoplasms originating from different tissues altogether. FDG-PET might not accurately reflect the malignant potential of musculoskeletal tumors, but rather might implicate cellular components included in the lesions. A high accumulation of FDG can be observed in histiocytic, fibroblastic, and some neurogenic lesions, regardless of whether they are benign or malignant. More specific uses of FDG-PET, such as grading, staging, and monitoring of musculoskeletal sarcomas, should be considered for each tumor of a different histologic subtype.

Bone Neoplasms↗

PubMed2002

Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis.

Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.

Adult↗

PubMed2002

Forward-dynamics simulation of anterior cruciate ligament forces developed during isokinetic dynamometry.

A mathematical (computer) model was developed and used to study the mechanics of the human knee during extension exercises employing an isokinetic dynamometer. All parts of the body were fixed to ground, except for the right shank and foot, which were free to move in the parasagittal plane. A linkage attached the dynamometer to the shank; tibiofemoral articulation consisted of single-point contact, allowing both sliding and rolling to occur. Physiologically based representations of ligaments and muscles imparted forces to the shank. A forward dynamics simulation was performed to calculate the forces developed in the knee for isokinetic speeds ranging from 0 (isometric exercise) to 300 degrees /s. Simulations were conducted for a constant-speed phase during isokinetic knee extension exercise. It was assumed for the duration of each simulated exercise that the quadriceps were fully activated and the other muscles were fully deactivated. The force in the anterior cruciate ligament was found to be governed by the force-velocity properties of the quadriceps; the model predicts that 300 deg/sec isokinetic exercise can reduce the force transmitted to the ACL by almost a factor of two compared with that present during isometric knee extension.

Anterior Cruciate Ligament↗

PubMed2002

Atypical growth plate closure: a possible chronic Salter and Harris Type V injury.

Salter-Harris Type V epiphyseal injury is relatively uncommon. The authors present a case involving the proximal tibia diagnosed both by radiologic and histologic findings. The findings suggest that Salter-Harris Type V injury can be a possible outcome when the disappearance of the physeal plate is reported in a patient who has great physical activity in childhood, even if the patient has suffered from no major injury.

Adolescent↗

PubMed2002

Testing trend for count data with extra-Poisson variability.

Trend tests for monotone trend or umbrella trend (monotone upward changing to monotone downward or vise versa) in count data are proposed when the data exhibit extra-Poisson variability. The proposed tests, which are called the GS1 test and the GS2 test, are constructed by applying an orthonormal score vector to a generalized score test under an rth-order log-linear model. These tests are compared by simulation with the Cochran-Armitage test and the quasi-likelihood test of Piegorsch and Bailer (1997, Statistics for Environmental Biology and Toxicology). It is shown that the Cochran-Armitage test should not be used under the existence of extra-Poisson variability; that, for detecting monotone trend, the GS1 test is superior to the others; and that the GS2 test has high power to detect an umbrella response.

Animals↗

PubMed2002

Pirarubicin-based versus doxorubicin-based osteosarcoma chemotherapy.

OBJECTIVE: To conduct a retrospective evaluation of tetrahydropyranyladriamycin (PIR)-based combination chemotherapy for osteosarcomas in comparison with doxorubicin (DOX)-based regimens to determine differences in response and toxicities between DOX- and PIR-containing regimens. METHODS: Toxicities and response rates of the 2 anthracyclines given as combination chemotherapy were assessed in patients with osteosarcoma, with 19 patients receiving PIR-based and 11 receiving DOX-based regimens. RESULTS: The survival of osteosarcoma patients treated with PIR was significantly better than that with DOX (p = 0.023) based on 2-year follow-up. Adverse effects such as mucositis and diarrhea were also less pronounced in the PIR cohort. CONCLUSIONS: PIR-based combination chemotherapy might be a useful and safe chemotherapeutic strategy for osteosarcomas compared with DOX regimens. Further assessment is necessary to confirm the safety and efficacy of this treatment.

Adolescent↗

PubMedDate not supplied

Effect of hamstrings muscle action on stability of the ACL-deficient knee in isokinetic extension exercise.

OBJECTIVE: To quantify the effect of hamstrings muscle action on stability of the anterior cruciate ligament deficient knee during isokinetic exercise at various speeds. DESIGN: Mathematical modeling and forward-dynamics computer simulation were used to study the interactions between knee-extension speed, hamstrings co-contraction activity, and anterior tibial translation in the intact and anterior cruciate deficient knee. BACKGROUND: There is much experimental evidence available to believe that hamstrings co-contraction can reduce anterior tibial translation in the anterior cruciate deficient knee. Little is known, however, about the level of hamstrings activation needed to keep anterior tibial translation within normal limits during functional activity. METHODS: Isokinetic knee-extension was simulated with a sagittal-plane model used previously to study load sharing between the muscles, ligaments, and bones during isometric knee-extension exercise, isokinetic exercise, and squatting exercise. CONCLUSIONS: Some amount of hamstrings activation is needed to stabilize an anterior cruciate deficient knee irrespective of how fast the knee extends. The level of hamstrings co-contraction needed to stabilize an anterior cruciate deficient knee is inversely related to extension speed. Hamstrings co-contraction is more effective in reducing anterior tibial translation than low-resistance extension exercise. RELEVANCE: Excessive anterior tibial translation during knee-extension exercise may lead to damage of the meniscus and other passive structures inside the knee. If anterior cruciate deficient patients can be trained to co-contract their hamstrings during isokinetic knee-extension, then this exercise is appropriate for maintaining strength of the thigh muscles without compromising the anterior stability of the knee.

Anterior Cruciate Ligament↗

PubMedDate not supplied

Evaluation of hemangioma by positron emission tomography: role in a multimodality approach.

PURPOSE: The relative utility of various preoperative diagnostic imaging modalities for the evaluation of hemangioma of the extremities, including positron emission tomography (PET) (using 18F-fluoro-2-deoxy-D-glucose [FDG] and fluorine-18 alpha-methyltyrosine [FMT]), computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA), was investigated. METHODS: Imaging findings in 16 patients with 16 histopathologically documented hemangiomas of the extremities were retrospectively reviewed. Preoperative imaging included: FDG-PET (n = 16), FMT-PET (n = 12), MRI (n =16), CT (n =11), and DSA (n =14). RESULTS: All 16 lesions examined by PET with FDG and/or FMT showed accumulation. The standardized uptake values (SUVs) for FDG-PET for the 16 examined tumors ranged from 0.7 to 1.67; for FMT-PET, they ranged from 0.14 to 1.00. The SUVs with both tracers indicated the benign nature of the tumor. Computed tomography demonstrated variable attenuation and phleboliths in two patients. The MRI signal characteristics were relatively consistent: heterogeneous signals were slightly higher than those of skeletal muscle on T1-weighted images and brighter than those of subcutaneous fat on T2-weighted images. The pooling and cotton-wool staining depicted in DSA was found to be significantly correlated with FDG accumulation, suggesting that localized blood retention-induced ischemia may accelerate anaerobic glycolysis, which leads to high FDG uptake. CONCLUSION: Although plain radiography, CT, MRI, and angiography may provide anatomic extent and be pathognomonic, FDG-PET and FMT-PET may be the most reliable among the studied imaging modalities for differentiating benign hemangiomas from other soft tissue tumors, especially malignant neoplasms.

Adolescent↗

PubMedDate not supplied

Carbon-11 choline positron emission tomography in musculoskeletal tumors: comparison with fluorine-18 fluorodeoxyglucose positron emission tomography.

PURPOSE: Recently, a new positron emission tomography (PET) tracer, carbon-11 choline, has been introduced in oncology investigations, but the role of choline PET in musculoskeletal tumor evaluation has not been previously examined. This is the first trial to investigate the utility of choline PET in evaluating musculoskeletal tumors in comparison with fluorine-18 fluoro-2-deoxy-D-glucose (FDG) PET. METHOD: Thirty-three patients were examined with both choline PET and FDG PET, of which standardized uptake values (SUVs) were used for evaluation of the lesions. To decide the appropriate cutoff value and compare the two PET studies, receiver operating characteristic curve analysis was used. The binomial test was used for comparison of sensitivities between choline PET and FDG PET. RESULTS: A significant correlation (r = 0.537, P = 0.0013) between choline and FDG SUVs was noted for all lesions (n = 33). Mean SUVs for malignant tumors were significantly higher than those for benign lesions in both choline PET and FDG PET. Using a cutoff value of 2.7 for choline SUVs, the sensitivity for correctly diagnosing malignancy was 92.3% (12/13) with a specificity of 90.0% (18/20), resulting in an accuracy rate of 90.9%. With use of a cutoff value of 3.3 for SUVs in FDG PET, the sensitivity was 84.6% (11/13) with a specificity of 80.0% (16/20), resulting in an accuracy rate of 81.8%. The receiver operating characteristic curves of two analyses showed that the mean area under the curve value of choline PET (0.9577 +/- 0.041) was significantly greater (P = 0.0488) than that of FDG PET (0.8192 +/- 0.0806). There was no significant difference in sensitivity and specificity between choline PET and FDG PET analysis using either the binomial test (P = 0.4531) or McNemar test (P = 0.371). CONCLUSION: Choline PET analysis may not be inferior to FDG PET analysis for differentiating malignant from benign musculoskeletal tumors. The advantages of choline PET were shorter examination time and little retention in the bladder; therefore, this modality may be useful for preoperative planning for musculoskeletal tumors, especially for lesions around the hip joints.

Adolescent↗

PubMedDate not supplied

Autocrine motility factor receptor gene expression and cell motility in lung cancer cell lines.

The cell motility of tumor cells is an integral component of tumor invasion and metastasis. Autocrine motility factor (AMF) stimulates cell motility via a receptor (R)-mediated signal pathway. We studied the correlation between level of AMF-R gene expression by reverse transcription-polymerase chain reaction and cell motility by phagokinetic track assay with or without AMF in lung cancer cell lines. Lung cancer cell lines with higher AMF-R gene expression tended to have greater cell motility than those with lower AMF-R gene expression with or without AMF. Most of lung cancer cell lines showed significantly increased motility with the stimulation of AMF. We conclude that the presence of higher AMF-R gene expression and tumor cell motility via receptor in response to the stimulation of AMF could be an important aspect in the invasion and metastasis of lung cancer cell lines.

Carcinoma, Non-Small-Cell Lung↗