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Biomedical subjects

Masaaki Takahashi

Publications and source records attributed to Masaaki Takahashi.

At least 19 recordsLinked to original sources
PubMed2006

The effect of methotrexate on bone metabolism markers in patients with rheumatoid arthritis.

The aim of the present study was to evaluate the influence on urinary excretion levels of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD) as a useful marker for bone resorption, and on serum-bone alkaline phosphate (BAP) levels as a useful marker for bone formation and an early marker of osteoblast differentiation in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Thirty patients with RA, diagnosed according to the criteria of the American College of Rheumatology, were involved in this study between March 2003 and January 2005. None of the patients had a history of hormone (estrogen) replacement therapy. All patients were treated with MTX. Methotrexate was administered perorally at a dosage of 4-10 mg/week. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, 3 months and 6 months after the initial treatment. Then the levels of NTX and DPD in urine and BAP in serum were measured in all patients. For comparison with the effect of other DMARDs on bone metabolism markers in RA patients, we measured the levels of NTX and DPD in urine and BAP in serum of RA patients, 13 patients treated with salazosulfapyridine (SASP), and 14 patients treated with actarit (ACT). In patients treated with MTX, NTX levels decreased significantly at 3 months after the initial treatment and remained low at 6 months after the initial treatment, and DPD levels significantly decreased at 6 months after the initial treatment. The mean serum BAP levels changed without significant differences from the baseline at 3 months and 6 months. In patients treated with SASP and ACT, all bone metabolism markers had not changed significantly at the three time points. On disease activity erythrocyte sedimentation rate, C-reactive protein, the number of swollen joints and tender joints, and mHAQ score decreased significantly at 3 months after the initial treatment, and remained at low levels at 6 months after the initial treatment with MTX. Methotrexate therapy looks promising in inhibiting generalized bone loss in patients with RA. In addition, NTX is a more sensitive marker than DPD.

Administration, Oral↗
PubMed2006

CD44-dependent intracellular and extracellular catabolism of hyaluronic acid by hyaluronidase-1 and -2.

Hyaluronic acid (HA) is a high molecular weight glycosaminoglycan involved in a wide variety of cellular functions. However, its turnover in living cells remains largely unknown. In this study, CD44, a receptor for HA, and hyaluronidase-1, -2, and -3 (Hyal-1, -2 and -3) were stably expressed in HEK 293 cells and the mechanism of HA catabolism was systematically investigated using fluorescein-labeled HA. CD44 was essential for HA degradation by both endogenous and exogenously expressed hyaluronidases. Hyal-1 was not able to cleave HA in living cells in the absence of CD44. Intracellular HA degradation was predominantly mediated by Hyal-1 after incorporation of HA by CD44. Although Hyal-1 was active only in intracellular space in vivo, a certain amount of the enzyme was secreted to extracellular space. This extracellular Hyal-1 was found to be incorporated by cells and such uptake of Hyal-1 was, in part, involved in the intracellular degradation of HA. Hyal-2 was involved in the extracellular degradation of HA. Hyal-2 activity was also dependent on the expression of CD44 in both living cells and enzyme assays. Immunofluorescent microscopy demonstrated that both Hyal-2 and CD44 are present on the cell surface. Without CD44 expression, Hyal-2 existed in a granular pattern, and did not show hyaluronidase activity, suggesting that localization change could contribute to Hyal-2 function. A convenient and quantitative enzyme assay was established for the measurement of Hyal-2 activity. Hyal-2 activity was detected in the membrane fraction of cells co-expressing Hyal-2 and CD44. The pH optimum for Hyal-2 was 6.0-7.0. The membrane fraction of cells expressing Hyal-2 alone did not show hyaluronidase activity. Hyal-3 did not show any hyaluronidase activity in our experimental conditions. Based on these findings, Hyal-1 and -2 contribute to intracellular and extracellular catabolism of HA, respectively, in a CD44-dependent manner, and their HA degradation occurs independently from one another.

Animals↗
PubMed2006

Anatomical study of the femoral and tibial insertions of the anterolateral and posteromedial bundles of human posterior cruciate ligament.

For posterior cruciate ligament (PCL) reconstruction, two root, anterolateral and posteromedial bundles restruction are performed. However, little has been mentioned of anatomical measurements of the insertions to the bone of these bundles in previous publications. The aim of this study is to determine the precise anatomical measurements of the femoral and tibial insertions for anterolateral and posteromedial bundles of PCL. A total of 32 femur and 33 tibiae were selected from 50 cadavers after exclusion of knees that displayed macroscopically degenerative changes or evidence of trauma. PCL were divided into anterolateral bundles and posteromedial bundles to the insertion footprint, and those locations were measured and described. The distance from the center of the femoral insertions of the anterolateral and posteromedial bundles, and the Wrisberg ligament to the anterior margin of the medial femoral condyle averaged 9.6, 10.6, and 17.1 mm, respectively. The distance from the center of the femoral insertions of the anterolateral, posteromedial bundles, and Wrisberg ligament to the intercondylar roof averaged 4.8, 11.4, and 10.4 mm, respectively. The distance from the medial margin of the articular cartilage of the tibial plateau to the center of the tibial insertions of the anterolateral and posteromedial bundles averaged 51.0 and 50.0% of the total widest width of the tibial plateau, respectively. The vertical distance from the tibial insertion of the center of the posteromedial bundle to the plane of the tibial articular surface averaged 4.6 mm. This study leads to a better definition of the anatomy of the anterolateral and posteromedial bundles of PCL. It is very important to know the precise anatomy of PCL bundles when performing PCL reconstruction, and to evaluate PCL reconstruction surgery on an anatomical basis.

Cadaver↗
PubMed2006

Cyclops syndrome occurring after chronic partial rupture of the anterior cruciate ligament without surgical reconstruction.

Cyclops syndrome is one of the specific causes of loss of extension of the knee following anterior cruciate ligament (ACL) reconstruction. This syndrome is manifest by progressive loss of knee extension associated with pain and audible clunk at terminal extension caused by a pedunculated nodule of fibrovascular proliferative tissue usually arising from a graft. Recent published reports, however, have described Cyclops syndrome also developing after a partial ACL rupture without surgical reconstruction. In most cases, Cyclops syndrome generally occurred within 2 months after reconstruction surgery or rupture. Here we report on the case of a patient with symptoms and arthroscopic and histological findings compatible with Cyclops syndrome that developed after a chronic partial ACL rupture that occurred 23 years ago. To our knowledge, this is the first case report of Cyclops syndrome occurring after chronic partial ACL rupture.

Adult↗
PubMed2006

Treatment with anti-TNF-alpha antibody infliximab reduces serum IL-15 levels in patients with rheumatoid arthritis.

The aim of this study was to analyze the change of serum cytokines and pentosidine levels in patients with rheumatoid arthritis (RA) by infliximab treatment. Twenty-three patients with RA were studied for 30 weeks on the effects of infliximab treatment. Serum levels of IL-15, IL-16, IL-17, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured with ELISA methods and pentosidine levels were determined using high-performance liquid chromatography, both at baseline and at 14 and 30 weeks after the initial treatment with infliximab. In addition, the patients also underwent physical and routine blood examinations. The higher levels of serum IL-15 in RA patients before treatment with infliximab significantly decreased at 14 and 30 weeks after the initial treatment with infliximab, but serum IL-16, IL-17, GM-CSF, and pentosidine levels did not decrease. The serum IL-17 and GM-CSF levels remained to be a limited detectable level at the pre- and posttreatment with infliximab. Infliximab treatment significantly lowered the serum levels of IL-15 in patients with RA. IL-15 is one of the crucial cytokines affected by infliximab.

Antibodies, Monoclonal↗
PubMed2006

Anatomical study of the femoral and tibial insertions of the anteromedial and posterolateral bundles of human anterior cruciate ligament.

BACKGROUND: Recently, anatomical anterior cruciate ligament reconstruction with 2-bundle reconstruction has been proposed. Few previous publications have mentioned anatomical measurements of the insertions of these bundles. PURPOSE: To determine the precise anatomical measurements of the femoral and tibial insertions for anteromedial and posterolateral bundles of anterior cruciate ligament grafts. STUDY DESIGN: Descriptive laboratory study. METHODS: Thirty-two femurs and 31 tibias were selected. The anterior cruciate ligament was divided into anteromedial and posterolateral bundles to the insertion footprint. Six measurements of the femoral insertion and 4 measurements of the tibial insertion were examined. Locations of the femoral insertions were examined using lateral radiographs of the femur. RESULTS: The distance between the center of the femoral insertions of the anteromedial and posterolateral bundles and the posterior margin of the lateral femoral condyle averaged 7.6 and 7.0 mm, respectively. The distance between the center of the femoral insertions of the anteromedial and posterolateral bundles to the intercondylar roof averaged 4.1 and 11.3 mm, respectively. The sagittal distance between the center of the tibial insertions of the anteromedial and posterolateral bundles from the anterior margin of the tibial articular cartilage averaged 13.0 and 14.7 mm, respectively. The distance from the lateral margin of the articular cartilage of the tibial plateau to the center of the tibial insertions of the anteromedial and posterolateral bundles averaged 44.2% and 52.4% of the total widest width of the tibial plateau, respectively. On the lateral radiograph of femoral condyles, the center of the anteromedial bundle was located at 31.9% from the posterior margin of the femoral condyle and 26.9% from the roof, and that of the posterolateral bundle was located at 39.8% from the posterior margin of the femoral condyle and 53.2% from the roof. CLINICAL RELEVANCE: It is important to know the precise anatomy of anterior cruciate ligament bundles when performing reconstruction and to evaluate anterior cruciate ligament reconstruction surgery on an anatomical basis.

Anterior Cruciate Ligament↗
PubMed2006

Mixed germinoma and choriocarcinoma in the intramedullary spinal cord: case report and review of the literature.

Primary germinomas in the spinal cord are very rare with only 15 cases published previously. In this case a 22-year-old woman with urinary incontinence, lumbago, and bilateral leg pain and weakness was found to have a solid tumor in the conus medullaris between the L1 and L2 vertebral bodies. Serum HCG was elevated without pregnancy. The pathological diagnosis was mixed germinoma and choriocarcinoma of the intramedullary spinal cord. She received craninospinal irradiation and three courses of chemotherapy and is currently asymptomatic with no evidence of recurrence and metastasis 22 months after surgery. To our knowledge, this is the first case report of a patient with a primary mixed germinoma and choriocarcinoma of the intramedullary spinal cord. The previous 15 cases of primary spinal cord germinoma have been reviewed for comparison.

Adult↗
PubMed2006

Pretreatment of polyamide monofilament with hydrochloric acid improves sensitivity of three-dimensional microarray, Bio-Strand.

A single-nucleotide-polymorphism-typing method using a novel three-dimensional DNA microarray, Bio-Strand, is promising because it is rapid, inexpensive and easily automated. It has been developed with the intent to overcome the drawbacks of conventional DNA microarrays, which use flat surfaces and impermeable materials such as glass slides; Bio-Strand as a novel DNA microarray, with its permeability, has a significantly improved stability compared with conventional DNA microarrays that use impermeable materials. In this study, we have developed a simple method of pretreating a polyamide monofilament to increase its surface area and to make it permeable, which makes Bio-Strand more sensitive and stable, allowing it to be adapted for clinical diagnostic applications. The fluorescence signal obtained with a nylon 6 monofilament pretreated under optimal conditions (hydrolysis by 5 M HCl/ethanol followed by washing with 50% ethanol and 100% ethanol) was significantly stronger than that obtained with an untreated monofilament.

Hydrochloric Acid↗
PubMed2005

The effect of hyaluronic acid with different molecular weights on collagen crosslink synthesis in cultured chondrocytes embedded in collagen gels.

Hyaluronic acid (HA) is a component of the extracellular matrix of cartilage and has various effects on three-dimensional cultured chondrocytes. We measured Pyridinoline (Pyr), which is a crosslink of collagen in cultured chondrocyte-collagen composites treated with HA of different molecular weights to investigate the effects of the various molecular weights on collagen crosslink synthesis. The control group was collagen gel without cells; group N was treated without HA; and the others were treated with HA with an average molecular weight of 2.3 x10(6) Da (group H), 8.0 x10(5) Da (group M), and 2.3 x10(4) Da (group L). In the control group, the Pyr content decreased, at week 4, being one-tenth that of preculture levels. In groups H and M, it was significantly greater than that in groups L and N at week 4. Pyr/hydroxyproline, which indicates the concentration of Pyr per collagen, decreased greatly in the control group at week 3. In groups H and M, it was significantly higher than that in groups L and N at week 4 and increased to 80 and 76% of normal rabbit articular cartilage, respectively. The concentration of Pyr per collagen in cultured chondrocyte-collagen composites was similar to that of normal articular cartilage in vivo, and higher molecular weight HA may have a greater effect on the maturation of collagen in the composite.

Amino Acids↗
PubMed2005

Ultrapure dialysate reduces plasma levels of beta2-microglobulin and pentosidine in hemodialysis patients.

BACKGROUND: beta2-Microglobulin (beta2MG) and carbonyl stress are reported to contribute to the development of dialysis-related amyloidosis. The aim of this study was to determine whether the purity of dialysate affects plasma levels of beta2MG and pentosidine (a surrogate marker of carbonyl stress) in hemodialysis patients. METHODS: Sixteen patients on hemodialysis with a polysulfone membrane participated in this study. We switched the dialysate from conventional dialysate (endotoxin level 0.055-0.066 endotoxin units (EU)/ml) to ultrapure dialysate (endotoxin level <0.001 EU/ml), followed patients for 6 months, and then switched back to conventional dialysate once again. Plasma levels of beta2MG, pentosidine, CRP and interleukin-6 (IL-6) were determined before the switch to ultrapure dialysate, 1 and 6 months after the switch to ultrapure dialysate, and 1 month after the switch back to conventional dialysate. RESULTS: The switch from conventional to ultrapure dialysate significantly decreased plasma levels of beta2MG, from 30.1 +/- 1.4 to 27.1 +/- 1.4 mg/dl (p < 0.05) and pentosidine, from 1,535.8 +/- 107.5 to 1,267.6 +/- 102.9 nmol/l (p < 0.01) after 1 month of use. The change of dialysate also significantly decreased plasma levels of CRP, from 0.28 +/- 0.09 to 0.14 +/- 0.05 mg/dl (p < 0.05) and IL-6, from 9.4 +/- 2.7 to 3.5 +/- 0.8 pg/ml (p < 0.01) over the 1-month period. These changes in plasma levels of beta2MG, pentosidine, CRP and IL-6 were maintained over 6 months after switching to ultrapure dialysate and returned to basal levels by switching back to a conventional dialysate. CONCLUSIONS: Ultrapure dialysate decreases plasma levels of beta2MG, pentosidine and inflammatory markers in hemodialysis patients. The use of ultrapure dialysate might be useful in preventing and/or treating complications of dialysis, such as dialysis-related amyloidosis, atherosclerosis and malnutrition.

Aged↗
PubMed2005

S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) influences cytotoxicity, translocating to the nucleus during apoptosis. Here we report a signalling pathway in which nitric oxide (NO) generation that follows apoptotic stimulation elicits S-nitrosylation of GAPDH, which triggers binding to Siah1 (an E3 ubiquitin ligase), nuclear translocation and apoptosis. S-nitrosylation of GAPDH augments its binding to Siah1, whose nuclear localization signal mediates translocation of GAPDH. GAPDH stabilizes Siah1, facilitating its degradation of nuclear proteins. Activation of macrophages by endotoxin and of neurons by glutamate elicits GAPDH-Siah1 binding, nuclear translocation and apoptosis, which are prevented by NO deletion. The NO-S-nitrosylation-GAPDH-Siah1 cascade may represent an important molecular mechanism of cytotoxicity.

Animals↗
PubMed2005

Altered patterns of blood flow response during visual stimulation in carotid artery occlusive disease.

To correctly interpret the results of functional neuroimaging studies in stroke, it is essential to understand how cerebrovascular disease influences hemodynamic response during neural activation. To investigate the effect of internal carotid artery (ICA) occlusive disease on the pattern of cerebral blood flow (CBF) response during visual stimulation, we used positron emission tomography to study 13 patients with ICA steno-occlusive lesions. We measured the changes of CBF during visual stimulation in the primary visual cortex and in the surrounding region, including the higher-order visual cortex, and examined their correlation with the baseline value of oxygen extraction fraction, a measure of hemodynamic impairment, in the ICA distribution. With visual stimulation, CBF in the primary visual cortex significantly increased in all patients, while in the surrounding region, CBF showed variable changes, including decreases in some patients. In 9 patients with unilateral ICA lesions, the CBF change in the surrounding region ipsilateral to the ICA lesion was significantly decreased compared with the value in the contralateral hemisphere, while the CBF change in the primary visual cortex showed no hemispheric difference. The hemispheric values of oxygen extraction fraction in the ICA distribution and the amount of CBF increase in the visual cortex were independently and negatively correlated with the CBF change in the surrounding region. We conclude that the pattern of CBF response during visual stimulation may change in ICA occlusive disease. We suggest that the redistribution of CBF during visual stimulation may be a contributing mechanism.

Aged↗
PubMed2005

The use of axial reconstructed images from three-dimensional MRI datasets for morphological diagnosis of meniscal tears of the knee.

INTRODUCTION: In recent years, three-dimensional (3D) MRI has been utilized to detect meniscal tears and has displayed several advantages over 2D MRI. The diagnostic performance to discriminate the type of meniscal tears by 2D MRI (sagittal and coronal images) and axial images from 3D MRI datasets has not been reported yet. The aim of the present study is to evaluate the efficacy of the axial reconstructed images from 3D MRI datasets for the morphological diagnosis of meniscal tears of the knee. MATERIALS AND METHODS: Seventy-four menisci in 37 patients who underwent arthroscopic surgery of the knee were studied. All patients were examined by 2D sagittal and coronal MRI and by axial images from 3D MRI datasets prior to surgery. First, we compared the diagnostic performance for meniscal tears by 2D sagittal and coronal MRI to that by axial images from 3D MRI datasets as judged by arthroscopic findings. Second, we compared the correlation of tear types presumed from 2D sagittal and coronal MRI to arthroscopy with those presumed from axial images from 3D MRI datasets to arthroscopy. RESULTS: For the diagnostic performance of meniscal tears on 2D MRI, the sensitivity, specificity and accuracy were 93.5%, 88.4% and 90.5%, respectively. On axial images from 3D MRI, the sensitivity, specificity and accuracy were 96.8%, 79.1% and 86.5%, respectively. Nine cases were false-positive on axial images, while 5 cases were false-positive on 2D images. Correlations to arthroscopy were 100% by both scans for longitudinal tears and discoid meniscus tears. Only 29% were correctly diagnosed by 2D sagittal and coronal images for radial tears, however, all radial tears could be correctly diagnosed by axial images. All horizontal tears were correctly diagnosed on 2D sagittal and coronal images, while none of the horizontal tears could be correctly diagnosed from axial images. CONCLUSION: Axial images from 3D MRI datasets were useful in the diagnosis of radial tears, but two limitations are noted concerning the use of axial images. First, medial menisci should be carefully read on axial slices because of the relatively high rate of false-positives on medial menisci. Second, axial images cannot discriminate horizontal tears from other types of meniscus tears.

Adolescent↗
PubMed2005

Arthroscopic treatment of popliteal cyst and visualization of its cavity through the posterior portal of the knee.

In regard to arthroscopic treatment of popliteal cysts, we explored the refuted pathology for popliteal cysts proposed by others. Here we introduce an arthroscopic technique using posterior portals to treat a popliteal cyst based on our observation that the opening of the cyst in the joint is a slit-like structure in the posterior wall of the capsule. By disrupting this slit-like structure with our procedure, the popliteal cyst ceased to be palpable and was no longer symptomatic. This technique also provides excellent arthroscopic visualization of the cavity of the popliteal cyst through the knee joint approach. After completion of the resection of the opening, we can easily insert an arthroscope into the cavity of the popliteal cyst from the posteromedial portal through the resected opening. Arthroscopic visualization of the cavity of the cyst showed that the inside wall of the cavity was smooth and had no synovitis. We believe that to disrupt this slit structure is the most pathologically reasonable procedure to treat popliteal cysts surgically.

Arthroscopy↗
PubMed2005

Conventional HPLC method used for simultaneous determination of the seven HIV protease inhibitors and nonnucleoside reverse transcription inhibitor efavirenz in human plasma.

We developed a simple HPLC method for the simultaneous quantitative determination of seven HIV protease inhibitors: amprenavir (APV), atazanavir (ATV), indinavir (IDV), lopinavir (LPV), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), and a nonnucleoside reverse transcription inhibitor, efavirenz (EFV). This method involves a rapid liquid-liquid drug extraction from plasma, the use of an isocratic elution on a reversed-phase C18 column, and an ultraviolet detection at a single wavelength (205 nm). The mobile phase consisted of 39% 50 mM phosphate buffer (pH 5.9), 22% methanol and 39% acetonitrile. Forty-eight samples could be measured in one day since the runtime of one sample is 30 min. The assay has been validated over a concentration range of 0.05 to 12.20 microg/ml for APV, 0.09 to 12.05 microg/ml for ATV, 0.05 to 12.01 microg/ml for IDV, 0.12 to 12.36 microg/ml for LPV, 0.18 to 12.20 microg/ml for NFV, 0.12 to 12.33 microg/ml for RTV, 0.12 to 12.06 microg/ml for SQV, and 0.05 to 12.17 microg/ml for EFV. Calibration curves were linear in the described concentration ranges. The average accuracy ranged from 97.2 to 106.8%. Both the interday and intraday coefficients of variation for all drugs tested were less than 8.5%. This method provides a simple, accurate, and precise method for the therapeutic drug monitoring of the seven protease inhibitors and EFV in clinical routine use.

Alkynes↗
PubMed2005

Development of an automation system for single nucleotide polymorphisms genotyping using bio-strand, a new three-dimensional microarray.

Previously, we developed a novel three-dimensional microarray system called Bio-Strand, which may be used in various applications including single nucleotide polymorphisms genotyping. In Bio-Strand, samples for detection are immobilized on a one-dimensional thread, which is wound around a cylinder-shaped core to form a three-dimensional thread-and-core structure. The thread-and-core structure is then inserted into a plastic pipette tip, where hybridization and detection are performed. In this study, we have developed an automation system, NIAGALA Bio-Station SDx, which enables automated hybridization and detection during the genotyping procedure using Bio-Strand. Using this system, we have performed the single nucleotide polymorphism (SNP) genotyping of CYP2C, one of the important human cytochrome P450 genes and the results were completely consistent with the genotyping results determined by the TaqMan method.

Algorithms↗