Biomedical subjects

Kensei Nagata

Publications and source records attributed to Kensei Nagata.

At least 19 recordsLinked to original sources

PubMed2006

Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells.

There is no established optimum treatment for malignant fibrous histiocytoma (MFH) at present, and few MFH cell lines are established. In the present study, we established new MFH cell lines, KHZ-MFH and SFT85-03, and investigated the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway. We found that MFH cells secreted high levels of IL-6 and that STAT3 was constitutively activated in these cells. The JAK2 kinase inhibitor, tyrphostin AG490, suppressed the growth of MFH cells and inhibited the secretion of IL-6. Furthermore, blockade of activated STAT3 by forced expression of a cytokine signaling repressor, SOCS3 gene as well as a dominant-negative STAT3 in these cells significantly suppressed their growth. These results indicated that an autocrine mechanism of the JAK/STAT3 signaling pathway could promote the growth of MFH cells and that this pathway could be a therapeutic target of MFH.

Aged↗

PubMed2006

Cervical spine disorders in farm workers requiring neck extension actions.

BACKGROUND: Cervical extension is considered a risk factor for provoking radicular and spinal cord compromise. However, there have been no reports on the relation between extension strain (ES) and cervical spine disorders: degenerative cervical spine disorders, dynamic canal stenosis (DCS), and cervical myelopathy. We performed a cross-sectional study to investigate the relation. METHODS: Orthopedic examinations were performed on 177 grape-growers (ES-exposed group) and 191 eggplant-growers (control group) between May and August 2000; and patients with degenerative cervical spine disorders, DCS, and cervical myelopathy were identified in the two groups. ES, degenerative cervical spine disorders, DCS, and cervical myelopathy were regarded as exposure variables; and age, sex, and working years were regarded as confounders. In cases where the subject was exposed to each exposure variable, multivariate-adjusted odds ratios to degenerative cervical spine disorders, DCS, and cervical myelopathy and multivariate-adjusted odds ratios regarding cervical myelopathy as the dependent variable were calculated by unconditional logistic regression analysis. RESULTS: Multivariate unconditional logistic regression analysis showed a significant odds ratio of ES to degenerative cervical spine disorders [2.72, 95% confidence interval (CI) 1.62-4.56]. Multivariate unconditional logistic regression analysis showed significant odds ratios for DCS (4.50, 95% CI 2.03-9.96) and age (1.07, 95% CI 1.01-1.14) regarding cervical myelopathy as the dependent variable. CONCLUSIONS: These findings suggested that ES of the cervical spine is a risk factor for degenerative cervical spine disorders, and DCS and the aging process are risk factors for cervical myelopathy.

Adult↗

PubMed2006

Improvement in knee extension strength through training by means of combined electrical stimulation and voluntary muscle contraction.

Weight training (WT) is the most common method of maintaining and increasing muscle strength. WT, however, is not always useful as it requires the external resistance and stabilization. We have developed a "hybrid training" (HYB) approach that avoids these problems by using electrically stimulated muscles to provide resistance to the motion of a muscle undergoing training. Here we report the efficacy of HYB compared with conventional WT for increasing the muscle strength around the knee at both slow and fast joint speeds (at 30 and 180 degrees /sec). Two matched groups, each of 8 healthy men aged 22 years, exercised 3 times/week for six weeks. Both groups showed significantly increased strength in concentric torque at 30 degrees /sec (HYB +28%, WT +33%) and at 180 degrees /sec (HYB +33%, WT +38%), and also in eccentric torque at 30 degrees /sec (HYB +25%, WT +24%) and at 180 degrees /sec (HYB +19%, WT +30%) (p < 0.001). HYB is comparable with WT exercising with the exception of high-speed contractions, while HYB has a clear advantage in not needing external resistance equipment or stabilization. HYB is therefore considered a useful approach for strengthening muscles when a person is restricted to bed rest or during space flight.

Adult↗

PubMed2006

Double-door laminoplasty using autologous spinous process for the management of cervical myelopathy.

We describe a technique of double-door laminoplasty for the management of cervical myelopathy using the autologous spinous process instead of an artificial spacer. The aims in the present study were to determine the fusion rate and the incidence rate of breakage in the autologous spinous process, and to assess its efficacy for cervical laminoplasty. Twenty-three patients of cervical myelopathy were treated with double-door laminoplasty followed by implantation of the autologous spinous process. The spinous process from C3 to C7 was resected, at 8 mm from the basal part of the spinous process. The autologous spinous process was made from the removed spinous process, and was implanted between each expanded laminae. Post-operative CT scanning determined the fusion rate between the expanded laminae and the autologous spinous process as 70.4% at 3 months, and 93.5% at 6 months, after the operation. There was no dissociation and no breakage in the autologous spinous process during the follow-up observation period. There were certain advantages to our technique including the high fusion rate and good stability in the autologous spinous process. In addition, this technique was less expensive than other techniques using an artificial spacer. These findings indicated that this technique was a reliable procedure for effectively treating of cervical myelopathy which are caused by multisegmental cervical canal stenosis.

Adult↗

PubMed2006

Advanced glycation end-products downregulating intervertebral disc cell production of proteoglycans in vitro.

OBJECT: The authors sought to clarify the role, if any, of advanced glycation end-products (AGEs) in disc degeneration. METHODS: Intervertebral discs were analyzed for the presence of AGEs and of their receptor (RAGE) by immunohistochemical analysis. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect any RAGE gene expression, and real-time PCR was used to quantify messenger RNA (mRNA) levels of aggrecan and collagen types I and II in nucleus pulposus cells treated with AGEs. Aggrecan protein concentration was determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis revealed that AGEs and RAGE were localized in the nucleus pulposus of the intervertebral disc. Advanced glycation end-products were found to significantly suppress the expression of aggrecan at both mRNA and protein levels in a dose- and time-dependent manner. The levels of collagen types I and II remained unchanged after treatments with AGEs. CONCLUSIONS: These results suggest that the accumulation of AGEs and their interaction with their receptor in the nucleus pulposus might result in the downregulation of aggrecan production responsible for disc degeneration.

Aged↗

PubMed2006

Muscle training by means of combined electrical stimulation and volitional contraction.

INTRODUCTION: A variety of techniques have been used with variable success in an attempt to reverse the loss of muscle strength, bulk, and endurance that occurs during spaceflight. This study was designed to evaluate a new "hybrid" approach that uses the resistance provided by an electrically stimulated antagonist muscle to resist the volitional contraction of its agonist. METHODS: There were 20 subjects who were randomized into 3 groups that received either the new hybrid program (HYB), isotonic weight training (WT), or isometric electrical stimulation (ES). Subjects trained 3 times per week for 8 wk with each session consisting of their non-dominant upper extremity performing 10 sets of 10 reciprocal 2-s elbow flexion and extension contractions separated by 1-min rest intervals. Elbow flexion\extension torques and biceps\triceps cross-sectional areas (CSA) were measured at the beginning, midpoint, and end of training as well as at follow-up 4 wk later. RESULTS: The HYB group demonstrated statistically significant increases in elbow flexion and extension torques (56% and 31%, respectively) at the end of training that were similar to or larger than the gains in the other groups with benefits that persisted at follow-up 4 wk later. Muscle CSA increases in the HYB group (10%) were comparable or larger than those in WT and ES subjects. CONCLUSIONS: These results suggest that HYB training may be an effective way to maintain and increase muscle bulk and strength for patients during bed rest, as well as astronauts in space.

Adult↗

PubMed2005

Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone.

UNLABELLED: The impact of AGEs on human MSCs was studied. AGEs inhibited the proliferation of MSCs, induced apoptosis, and prevented cognate differentiation into adipose tissue, cartilage, and bone, suggesting a deleterious effect of AGEs in the pathogenesis of musculoskeletal disorders in aged and diabetic patients. INTRODUCTION: Advanced glycation end-products (AGEs) are accumulated on long-lived proteins of various tissues in advanced age and diabetes mellitus and have been implicated in chronic complication, including musculoskeletal disorders. Human mesenchymal stem cells (MSCs) potentially differentiate into mature musculoskeletal tissues during tissue repair, but the pathogenetic role of AGEs on MSCs is unclear. MATERIALS AND METHODS: AGEs were prepared by incubating BSA with glucose, glyceraldehydes, or glycolaldehyde (designated as AGE-1, AGE-2, or AGE-3, respectively). Proliferation, apoptosis, and reactive oxygen species (ROS) generation were assayed in AGE-treated cells. The expression of the receptor for AGE (RAGE) was examined by immunohistochemistry and Western blotting. Involvement of RAGE-mediated signaling was examined using a neutralizing antiserum against RAGE. Differentiation into adipose tissue, cartilage, and bone were morphologically and biochemically monitored with specific markers for each. RESULTS: AGE-2 and AGE-3, but not control nonglycated BSA and AGE-1, reduced the viable cell number and 5-bromo-2'deoxyuridine (BrdU) incorporation with increased intracellular ROS generation and the percentage of apoptotic cells. MSCs expressed RAGE and its induction was stimulated by AGE-2 and AGE-3. These AGEs inhibited adipogenic differentiation (assayed by oil red O staining, lipoprotein lipase production, and intracellular triglyceride content) and chondrogenic differentiation (assayed by safranin O staining and type II collagen production). On osteogenic differentiation, AGE-2 and AGE-3 increased alkaline phosphatase activity and intracellular calcium content; however, von Kossa staining revealed the loss of mineralization and mature bone nodule formation. The antiserum against RAGE partially prevented AGE-induced cellular events. CONCLUSION: AGE-2 and AGE-3 may lead to the in vivo loss of MSC mass and the delay of tissue repair by inhibiting the maturation of MSC-derived cells. The AGE-RAGE interaction may be involved in the deleterious effect of AGEs on MSCs.

Acetaldehyde↗

PubMed2005

Computer-assisted measurement of the size of ossification in patients with ossification of the posterior longitudinal ligament in the cervical spine.

BACKGROUND: Progression of ossification of the posterior longitudinal ligament in patients may lead to serious neurological deterioration. A government-funded study group established a manual method of measurement on plain radiographs to detect progression of the ossified lesion. However, this method did not gain wide acceptance because it was time-consuming and complicated, for which drawings of many lines and points are required. We have applied a computer-assisted measurement system to this task and have evaluated inter- and intraexaminer reliability, showing that it is quicker to use and more accurate than the manual method. METHODS: Eight board-certified spine surgeons, acting as the examiners, measured the sizes of the ossified lesions on nine lateral cervical spine radiographs using the computer-assisted measurement system. Following insertion of digitized radiographic image data into a computer, the corners of the vertebral bodies on the displayed images are marked by the examiners, and the software automatically sets reference lines and points. The examiners identify upper, lower, and posterior margins of the ossified lesions, and the software calculates the dimensions of the ossified lesions. Data obtained from eight examiners for length and thickness underwent rigorous statistical analysis by calculating the intraclass correlation coefficients with 95% confidence intervals (CIs) to determine interexaminer reliability and Pearson's correlation coefficients between the two measurements by the same examiner to determine intraexaminer reliability. RESULTS: The intraclass correlation coefficients were 0.927 and 0.968 with 95% CIs of 0.883-0.955 and 0.956-0.978 for measurements of length and thickness, respectively, of the ossified lesions. The Pearson's correlation coefficients for the two measurements by the same examiners were 0.943-0.985 for length and 0.957-0.991 for thickness. CONCLUSIONS: The inter- and intraexaminer reliability using this measurement system was excellent. The method can detect progression of ossification of the posterior longitudinal ligament (OPLL) on plain radiographs with high precision and could become a standard method for measuring the size of OPLL.

Cervical Vertebrae↗

PubMed2005

Cartilage change after arthroscopic repair for an isolated meniscal tear.

To investigate the direct effect to the cartilage caused by the meniscal repair, we examined patients who underwent an isolated meniscal repair without any other abnormalities by arthroscopic examination. A total of 17 patients were examined by second-look arthroscopy after an average interval of 9 months from the meniscal repair, and have been evaluated the status of the repaired meniscus and of the relative femoral condylar cartilage. Changes in the severity of the cartilage lesion between at the time of meniscal repair and the time of the second-look arthroscopy were considered based on the status of the repaired meniscus. Regardless of the healing status of the repair site, it was possible to prevent degeneration in the cartilage in 9 of the 10 patients who demonstrated no degeneration in the meniscal body. Of the 7 patients who demonstrated degeneration in the meniscal body, progression in cartilage degeneration was noted as 1 grade in 2 patients and 2 grades in another 3 patients. Even in those in which stable fusion of the repair site was achieved, the condition of the inner meniscal body was not necessarily maintained favorably in all cases, indicating that degeneration in the meniscal body was a risk factor for cartilage degeneration. It was concluded that recovery could not be expected even at 9 months after the repair if the lesion had already demonstrated degeneration in the meniscal body at the time of repair.

Adolescent↗

PubMed2005

Nitric oxide regulation system in degenerative lumbar disease.

Elevated nitric oxide (NO) production derived from NO synthase (NOS) activity has been shown in cerebrospinal fluid (CSF) in patients with degenerative lumbar disease (DLD). However, the regulatory mechanism of NO and the relationship of NO to clinical manifestations are unclear. In the present study, concentrations of NOx (nitrate NO3- and nitrite, NO2-), L-arginine (a substrate for NOS), and asymmetric dimethyl arginine (ADMA, an endogenous NOS inhibitor) in CSF were measured in two major DLDs: lumbar intervertebral disc herniation (LDH; 13 cases) and lumbar spinal canal stenosis (LSCS; 28 cases), and were compared with the levels in control patients with traumatic diseases. The levels of NO regulatory markers were also assessed according to Japanese Orthopedic Association (JOA) scores for the management of low back pain. NOx levels in LSCS patients (9.65 +/- 0.74 microM) were significantly higher than those in controls (5.26 +/- 0.27 microM) and in LDH patients (4.27 +/- 0.35 microM) (p < 0.01). ADMA levels were lower in LDH patients (0.016 +/- 0.008 pM) than in controls (0.045 +/- 0.011 pM) (p < 0.05), whereas those in LSCS patients (0.05 +/- 0.006 pM) were the same as in the controls. There was no significant difference in L-arginine levels among the groups. Nitrate or nitrite levels in these DLDs correlated with some of the JOA scores. The NO2- concentration was positively correlated with both JOA15 and JOA6 scores in LDH cases (p < 0.01). In LSCS cases, a positive correlation was found between NO2- concentration and JOA6 score, and between NO3- concentration and JOA9 (p < 0.01). In immunohistochemical analysis, inducible NOS and dimethylarginine dimethylaminohydrolase were expressed in mononuclear cells in tissues obtained from LSCS patients along with nitrotyrosine deposition, a footprint of NO radical formation. Our data suggested that the NO regulatory mechanism controlling the pathogenesis and progression of LDH might differ from that of LSCS.

Adolescent↗

PubMed2005

Lipoma with dumb-bell extradural extension through the intervertebral foramen into the spinal canal. Case report.

The authors present the case of a 60-year-old woman with a neck lipoma that developed dumb-bell extradural extension, causing radiculopathy. To the best of the authors' knowledge, this is the first report of a lipoma originating in the neck with dumb-bell extradural extension through the intervertebral foramen and into the spinal canal. The lipoma was first excised from the foramen via a posterior approach to allow decompression of the nerve roots. The remaining lipomatous tissue was then resected via an anterior approach to avoid the region around the vertebral artery.

Cervical Vertebrae↗

PubMed2005

Positive feedback loop of interleukin-1beta upregulating production of inflammatory mediators in human intervertebral disc cells in vitro.

OBJECT: Interleukin-1beta (IL-1beta) induces neurological symptoms in intervertebral disc herniation (IDH). Recently, the existence of a positive feedback loop of IL-1beta, which encourages an inflammatory reaction or degeneration in the cells of tendon, has been reported. The authors hypothesized that there is a positive feedback loop of IL-1beta in the cells of IDH. METHODS: Eight human intervertebral disc specimens were harvested during spinal surgery for lumbar disc herniation. The cells were stimulated in serum-free medium with or without exogenous IL-1beta. The messenger RNA (mRNA) was extracted for reverse-transcription polymerase chain reaction (PCR) and real-time PCR to quantify the mRNA of endogenous IL-1beta, IL-6, cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs). The cells were then stimulated in serum-free medium with or without exogenous IL-1beta, and then exogenous IL-1beta was removed. After 2, 4, and 6 days, the medium was collected, and enzyme-linked immunosorbent assay was used to measure the protein concentration of endogenous IL-1beta. The mRNA expressions of endogenous IL-1beta, IL-6, COX-2, and MMPs were increased significantly depending on the concentration of exogenous IL-1beta. The protein concentration of endogenous IL-1beta was increased over time. CONCLUSIONS: There was a positive feedback loop of IL-1beta in the cells of IDH. Furthermore, the productions of IL-6, COX-2, MMP-1, and MMP-3 were upregulated as a result of the increasing concentration of IL-1beta in a positive feedback loop of IL-1beta. The authors concluded that this positive feedback loop of IL-1beta upregulated the production of mediators and thus can cause cessation of symptoms in IDH.

Adolescent↗

PubMed2004

Ghrelin directly regulates bone formation.

UNLABELLED: To clarify the role of ghrelin in bone metabolism, we examined the effect of ghrelin in vitro and in vivo. Ghrelin and its receptor, GHS-R1a, were identified in osteoblasts, and ghrelin promoted both proliferation and differentiation. Furthermore, ghrelin increased BMD in rats. Our results show that ghrelin directly affects bone formation. INTRODUCTION: Ghrelin is a gut peptide involved in growth hormone (GH) secretion and energy homeostasis. Recently, it has been reported that the adipocyte-derived hormone leptin, which also regulates energy homeostasis and opposes ghrelin's actions in energy homeostasis, plays a significant role in bone metabolism. This evidence implies that ghrelin may modulate bone metabolism; however, it has not been clarified. To study the role of ghrelin in skeletal integrity, we examined its effects on bone metabolism both in vitro and in vivo. MATERIALS AND METHODS: We measured the expression of ghrelin and growth hormone secretagogue receptor 1a (GHS-R1a) in rat osteoblasts using RT-PCR and immunohistochemistry (IHC). The effect of ghrelin on primary osteoblast-like cell proliferation was examined by recording changes in cell number and the level of DNA synthesis. Osteoblast differentiation markers (Runx2, collagen alpha1 type I [COLI], alkaline phosphatase [ALP], osteocalcin [OCN]) were analyzed using quantitative RT-PCR. We also examined calcium accumulation and ALP activity in osteoblast-like cells induced by ghrelin. Finally, to address the in vivo effects of ghrelin on bone metabolism, we examined the BMD of Sprague-Dawley (SD) rats and genetically GH-deficient, spontaneous dwarf rats (SDR). RESULTS: Ghrelin and GHS-R1a were identified in osteoblast-like cells. Ghrelin significantly increased osteoblast-like cell numbers and DNA synthesis in a dose-dependent manner. The proliferative effects of ghrelin were suppressed by [D-Lys(3)]-GHRP-6, an antagonist of GHS-R1a, in a dose-dependent manner. Furthermore, ghrelin increased the expression of osteoblast differentiation markers, ALP activity, and calcium accumulation in the matrix. Finally, ghrelin definitely increased BMD of both SD rats and SDRs. CONCLUSIONS: These observations show that ghrelin directly stimulates bone formation.

Adipocytes↗

PubMed2004

A long-term follow-up study of four cases who underwent curettage and autogenous bone grafting for steroid-related osteonecrosis of the femoral condyle.

We performed curettage followed by autogenous bone grafting in several cases of steroid-related osteonecrosis of the femoral condyle, and reviewed the outcome of this procedure after a mean follow-up of 9.5 years. The number of patients was 4; the mean age at the time of the operation was 30.5 years. The mean Knee Society Objective Score was 52.5 before the operation and had increased to 87.5 at the time of the review. The pre-operative radiographic stages were stage 2 in 2 patients and stage 3 in the other 2 patients. Progression in the disease stage was observed in 3 patients. MRI revealed survival of the grafted bone in only one case, and collapse of the articular surface in all cases. In conclusion, though the clinical results showed improvement, the autogenous bone graft failed to answer the purpose of preventing the progression in disease stage.

Adult↗

PubMed2004

[BMP and LMP-1 for intervertebral disc regeneration].

Some evidence indicates that intervertebral disc degeneration is associated with decreasing of matrix synthesis from disc cell. BMP-2 increased mRNA of aggrecan and Type II collagen. It also enhanced disc matrix (proteoglycan) production. Adenovirually mediated LMP-1 overexpression in intervertebral disc cells increased disc cell proteoglycan production through BMP-2 and BMP-7 mediated process.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Minimally invasive uncemented total hip arthroplasty through an anterolateral approach with a shorter skin incision.

Total hip arthroplasty using a short skin incision has been associated with great controversy. It has still not yet been demonstrated that a shorter skin incision is efficient or safe for patients. Here, we review 212 cases of uncemented total hip arthroplasty performed since 1999 using the anterolateral approach and a shorter skin incision. Patients were divided into three groups according to the length of the incision at the end of surgery; incisions of 10 cm or less were defined as "mini" ( n = 115) and incisions of 10-15 cm as "short" ( n = 70); these two groups were defined as shorter skin incision groups. Incisions longer than 15 cm in patients undergoing the standard procedure were defined as "conventional" and served as the controls ( n = 27). Statistically significant differences were found with regard to operative duration and intraoperative blood loss: the shorter the length of the incision, the shorter the operative duration and the smaller the intraoperative blood loss. There was no significant difference in postoperative bleeding or in the incidence of complications among the three groups. Total blood losses in the shorter groups were each statistically significant less than that in the conventional group. Comparing the mini group to the short group, the length of the skin incision was influenced by the body mass index (BMI) and gender. For those with a high BMI and for male patients, a slightly longer incision was necessary. We concluded that total hip arthroplasty through a mini or short incision was indeed efficient for patients compared with total hip arthroplasty using a conventional incision.

Adult↗

PubMed2003

Agonist contractions against electrically stimulated antagonists.

OBJECTIVE: To assess an exercise program that uses electrically stimulated antagonists to resist agonist muscle contractions. DESIGN: In 1 limb, electrically stimulated antagonists resisted elbow flexion and extension. In the other, stimulation occurred without volitional muscle contraction. SETTING: A biomechanics laboratory in Japan. PARTICIPANTS: Twelve men between the ages of 19 and 24 years. Subjects served as their own controls. INTERVENTION: Subjects trained 3 times a week for 12 weeks. Each session consisted of 10 sets of 10 elbow flexor and extensor contractions. MAIN OUTCOME MEASURES: Isokinetic elbow extension and flexion torques. Biceps and triceps brachii cross-sectional areas. RESULTS: Elbow extension torques increased (32.85% at 30 degrees/s, 27.20% at 60 degrees/s, 26.16% at 90 degrees/s; all P<or=.02) over the training period in limbs that trained against electrically stimulated antagonists. Control limb extension torque increases were smaller (8.52% -14.91%) and did not reach statistical significance. Elbow flexion torques improved in both groups, but the changes did not reach statistical significance. Cross-sectional areas increased in all muscles but were most marked in the antagonist stimulated limbs: triceps 16.20% versus 4.25% (P=.01) and biceps 16.65% versus 7.00% (P=.005). CONCLUSIONS: Exercises that use electrically stimulated antagonist muscles may be effective in increasing muscle strength and mass.

Adult↗

PubMed2003

Anteromedial meniscofemoral ligament.

We have experienced 3 cases of comparatively rare anteromedial meniscofemoral ligament in which the anterior horn of the medial meniscus was attached to the posterolateral wall of the femoral intercondylar fossa. In 2 of these cases, there was no attachment to the tibia, whereas in the other, it was connected to the lateral meniscus and also firmly to the tibia. In the 2 with no attachment to the tibia, abnormal mobility in the medial meniscus accompanied by flexion and extension of the knee was observed. Degeneration of the intermediate posterior segment and injury of the anterior horn were also observed. This anomaly induces a future meniscus injury, depending on the attachment state to the tibia.

Adolescent↗