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Biomedical subjects

Kozo Nakamura

Publications and source records attributed to Kozo Nakamura.

At least 73 records · Page 4Linked to original sources
PubMed2005

Insulin receptor substrate-1 is required for bone anabolic function of parathyroid hormone in mice.

Bone anabolic action of PTH has been suggested to be mediated by induction of IGF-I in osteoblasts; however, little is known about the molecular mechanism by which IGF-I leads to bone formation under the PTH stimulation. This study initially confirmed in mouse osteoblast cultures that PTH treatment increased IGF-I mRNA and protein levels and alkaline phosphatase activity, which were accompanied by phosphorylations of IGF-I receptor, insulin receptor substrate (IRS)-1 and IRS-2, essential adaptor molecules for the IGF-I signaling. To learn the involvement of IRS-1 and IRS-2 in the bone anabolic action of PTH in vivo, IRS-1-/- and IRS-2-/- mice and their respective wild-type littermates were given daily injections of PTH (80 mug/kg) or vehicle for 4 wk. In the wild-type mice, the PTH injection increased bone mineral densities of the femur, tibia, and vertebrae by 10-20% without altering the serum IGF-I level. These stimulations were similarly seen in IRS-2-/- mice; however, they were markedly suppressed in IRS-1-/- mice. Although the PTH anabolic effects were stronger on trabecular bones than on cortical bones, the stimulations on both bones were blocked in IRS-1-/- mice but not in IRS-2-/- mice. Histomorphometric and biochemical analyses showed an increased bone turnover by PTH, which was also blunted by the IRS-1 deficiency, though not by the IRS-2 deficiency. These results indicate that the PTH bone anabolic action is mediated by the activation of IRS-1, but not IRS-2, as a downstream signaling of IGF-I that acts locally as an autocrine/paracrine factor.

Animals↗
PubMed2005

High-performance liquid chromatographic determination of phenolic compounds in rice.

A method has been developed for the determination of 6'-O-feruloylsucrose, 6'-O-sinapoylsucrose, ferulic acid, sinapinic acid, p-coumaric acid, chlorogenic (3-caffeoylquinic) acid, caffeic acid, protocatechuic acid, hydroxybenzoic acid, vanillic acid, and syringic acid in rice. The rice samples were extracted with 70% ethanol, filtered, and defatted. The defatted aqueous solution was subjected to solid-phase extraction using a C18 silica gel cartridge; no analyte was lost in this procedure. The 70% acidic methanol elution was analyzed directly by HPLC and HPLC-ESI-MS. Phenolic compounds were separated with a C18 reversed-phase column by gradient elution using 0.025% trifluoroacetic acid in purified water (A)--acetonitrile (B) (0 min, 5% B; 5 min, 9% B; 15 min, 9% B; 22 min, 11% B; and 38 min, 18% B) as the mobile phase at a flow rate of 0.8 ml/min. Detection limits ranged from 0.10 to 0.35 ng per injection (5 microl). Relative standard deviations of 0.22-3.95% and recoveries of 99-108% were obtained for simultaneous determination of these phenolic compounds. This method was applied to analysis of phenolic compounds in brown rice and germinated brown rice soaked in 32 degrees C water for varying durations.

Chromatography, High Pressure Liquid↗
PubMed2005

Measurement of the tensile forces during bone lengthening.

BACKGROUND: The purpose of this study was to investigate the effects of lengthening frequency on mechanical environment in limb lengthening. METHODS: Tensile forces were continuously monitored using a load sensor attached to a unilateral external fixator. Twenty patients were monitored. Ten patients were with acquired femoral shortening, and five of them underwent quasi-continuous lengthening of 1440 steps per day, and the other five received step lengthening twice a day. The other 10 patients were with achondropalsia. Five of them underwent the same quasi-continuous lengthening, and the other five received the same step lengthening. The circadian change and the daily course of the tensile forces were assessed and compared between quasi-continuous lengthening and step lengthening. FINDINGS: As for circadian change, an acute increase in the force took place simultaneously with each step of lengthening in the step-lengthening group, but very little change of the baseline force level was seen during quasi-continuous lengthening. As for daily course of the tensile force, it increased almost linearly in both lengthening frequency groups in the initial stage of lengthening. No significant difference of the average force increment rate in this phase was recognized between the quasi-continuous and step lengthening groups irrespective of the etiologies. INTERPRETATION: The lengthening frequency greatly affected the circadian change of the tensile force, but did not affect the increment rate of the force in the linear phase.

Adolescent↗
PubMed2005

An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis.

Osteoarthritis is the most common form of human arthritis. We investigated the potential role of asporin, an extracellular matrix component expressed abundantly in the articular cartilage of individuals with osteoarthritis, in the pathogenesis of osteoarthritis. Here we report a significant association between a polymorphism in the aspartic acid (D) repeat of the gene encoding asporin (ASPN) and osteoarthritis. In two independent populations of individuals with knee osteoarthritis, the D14 allele of ASPN is over-represented relative to the common D13 allele, and its frequency increases with disease severity. The D14 allele is also over-represented in individuals with hip osteoarthritis. Asporin suppresses TGF-beta-mediated expression of the genes aggrecan (AGC1) and type II collagen (COL2A1) and reduced proteoglycan accumulation in an in vitro model of chondrogenesis. The effect on TGF-beta activity is allele-specific, with the D14 allele resulting in greater inhibition than other alleles. In vitro binding assays showed a direct interaction between asporin and TGF-beta. Taken together, these findings provide another functional link between extracellular matrix proteins, TGF-beta activity and disease, suggesting new therapeutic strategies for osteoarthritis.

Aggrecans↗
PubMed2005

Inhibition of Cdk6 expression through p38 MAP kinase is involved in differentiation of mouse prechondrocyte ATDC5.

Because a temporal arrest in the G1-phase of the cell cycle is a prerequisite for cell differentiation, this study investigated the involvement of cell cycle factors in the differentiation of cultured mouse prechondrocyte cell line ATDC5. Among the G1 cell cycle factors examined, both protein and mRNA levels of cyclin-dependent kinase (Cdk6) were downregulated during the culture in a differentiation medium. The protein degradation of Cdk6 was not involved in this downregulation because proteasome inhibitors did not reverse the protein level. When inhibitors of p38 MAPK, ERK-1/2, and PI3K/Akt were added to the culture, only a p38 MAPK inhibitor SB203580 blocked the decrease in the Cdk6 protein level by the differentiation medium, indicating that the Cdk6 inhibition was mediated by p38 MAPK pathway. In fact, p38 MAPK was confirmed to be phosphorylated during differentiation of ATDC5 cells. Enforced expression of Cdk6 in ATDC5 cells blocked the chondrocyte differentiation and inhibited Sox5 and Sox6 expressions. However, the Cdk6 overexpression did not affect the proliferation or the cell cycle progression, suggesting that the inhibitory effect of Cdk6 on the differentiation was exerted by a mechanism largely independent of its cell cycle regulation. These results indicate that Cdk6 may be a regulator of chondrocyte differentiation and that its p38-mediated downregulation is involved in the efficient differentiation.

Animals↗
PubMed2005

Spinal stenosis in grade I degenerative lumbar spondylolisthesis: a comparative study of outcomes following laminoplasty and laminectomy with instrumented spinal fusion.

The management of grade I lumbar degenerative spondylolisthesis remains controversial. There have been few reports comparing any form of surgery with conservative treatment. As for surgical management, the need for arthrodesis with instrumentation has not been established. A series of 53 patients with single-level spinal stenosis at L4/5 due to grade I degenerative spondylolisthesis entered into a study to compare outcomes of two surgical methods of treatment with those of a control group treated conservatively: group 1, 19 patients treated by decompression laminectomy combined with posterolateral fusion and pedicle screw instrumentation; group 2, 18 patients treated by decompression of the spinal canal using a laminoplasty technique to preserve the integrity of the midline structure; group 3, 16 patients treated conservatively after being recommended that they have surgery. We compared the 2-year results among the three groups. Alleviation of symptoms was noted in groups 1 and 2, whereas the controls (group 3) showed no improvement. There was no significant difference in the degree of clinical improvement between groups 1 and 2. Spondylolisthesis was controlled in group 1, but it did not lead to better clinical results than those achieved in group 2. Our findings indicate that the technique for decompressing the spinal canal with preservation of the posterior elements of its roof can be useful for treating patients with grade I degenerative spondylolisthesis with symptoms of spinal stenosis.

Aged↗
PubMed2005

Revision cervical spine surgery using transarticular or pedicle screws under a computer-assisted image-guidance system.

BACKGROUND: The exact insertion of a cervical screw is technically demanding, especially when normal anatomic landmarks have been obscured and are difficult to identify, such as in revision surgery. The purpose of this study was to evaluate the efficacy of an image-guidance system to aid placement of transarticular and pedicular screws for revision cervical spine surgery. METHODS: Ten patients with recurrent myelopathy, including seven with cerebral palsy, two with a giant cell tumor, and one with rheumatoid arthritis, underwent computer-aided reconstruction surgery. The authors used a frameless stereotactic image-guidance system with simultaneous fluoroscopy. Postoperative computed tomography was used to determine the accuracy of the screw placement. RESULTS: There were no neurovascular complications and no correction loss. All patients showed solid bony union. All four C1/2 transarticular screws were exactly placed inside the pedicles. Of 47 pedicular screws, 11 showed a slight breach of the cortex. When a reference arc could not be attached to the relevant vertebra, the rate of cortical perforation of screws was high (5/10; 50%) compared with the rate when a reference arc was attached to the relevant vertebra (6/37; 16%). CONCLUSION: Although more advanced technology is hopeful, a computer-assisted image-guidance system with simultaneous fluoroscopy is useful for aiding revision surgery to achieve rigid fixation and ensure safety.

Bone Screws↗
PubMed2005

Repeated postoperative laryngeal obstruction due to bilateral cricoarytenoid joint involvement in rheumatoid arthritis.

A 61-year-old woman with a 40-year history of severe rheumatoid arthritis developed postoperative laryngeal obstruction twice; the first episode occurred just after surgery for cervical myelopathy and the second episode occurred 3 weeks after surgery when physiotherapy activity increased. A flexible laryngeal endoscopy demonstrated that abduction of the bilateral vocal cords was severely disturbed at the paramedian position, suggesting a diagnosis of cricoarytenoid arthritis. Early administration of corticosteroids was successful.

Journal Article↗
PubMed2005

Bone resorption of the facet joint in rheumatoid arthritis as a predictor of lower cervical myelopathy.

The purpose of the present study was to identify the risk factors to predict instability of the subaxial cervical spine and cervical myelopathy based on plain radiographs. The study was performed on 99 patients with mutilating rheumatoid arthritis (RA). From plain lateral radiographs of the cervical spine over time, rheumatoid cervical spine lesions were investigated and evaluation was made on the possibility to develop cervical myelopathy. The incidence of subaxial cervical spine lesions in the patients with mutilating RA was as high as 98%. In particular, resorption of the superior facet suggests high risk to develop cervical myelopathy. The presence of spinous process erosion is also likely to reveal such a possibility. There was no statistically significant difference in the anteroposterior diameter of cervical spinal canal between the cases with cervical myelopathy and those without it. Resorption of the superior facet is the most important factor for the development of cervical myelopathy. In the cases with rheumatoid cervical spine lesions, it is necessary to take special notice of the superior facet.

Journal Article↗
PubMed2005

Involvement of cyclic guanosine monophosphate-dependent protein kinase II in chondrocyte hypertrophy during endochondral ossification.

During vertebrate skeletal development, the appendicular skeleton forms through endochondral ossification, which involves the intricately regulated multistep differentiation of mesenchymal cells. During this process, mesenchymal condensations initially differentiate into chondrocytes. Then chondrocytes in the center further differentiate into hypertrophic chondrocytes. Hypertrophic chondrocytes express a number of osteogenic factors and induce bone formation. Although numerous studies have provided novel insights into the regulation and function of cartilage development, little is known about the intracellular signaling pathways regulating chondrocyte hypertrophy. Recent study revealed that cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (cGKII) coupled the stop of proliferation and the start of hypertrophic differentiation of chondrocytes. Herein, we review the molecular mechanism of regulation of chondrocyte hypertrophy by cGKII and the interaction between cGKII and other signaling pathways.

Journal Article↗
PubMed2005

Osteogenesis and angiogenesis in regenerating bone during transverse distraction: quantitative evaluation using a canine model.

For some patients with a bone defect, curved deformity, or small diameter bone, transverse distraction might be better indicated than bone transport or lengthening. However, detailed quantitative evaluation of osteogenesis or angiogenesis during transverse distraction by creating a well-controlled animal model has not been done. We established a transverse distraction model of the canine tibia. A rectangular cortex was separated for a distraction fragment. Seven days after the operation, 0.5-mm distraction was applied twice daily for 14 days. After a 28-day consolidation period, the animals were sacrificed. Quantitative evaluations of the rates of mineralization and the increases of bone mineral density indicated faster mineralization and earlier corticalization of the regenerating bone in the initial stage of the consolidation period. The average blood vessel volume ratio in the distraction area was more than three times greater than in the intact contralateral tibiae. We hypothesized that adequate preservation of the marrow arteries and stability of the distraction site throughout an experimental period could induce this faster osteogenesis. Our results indicated that the transverse distraction technique was feasible. The transverse distraction technique could be indicated for patients with small-diameter bones or with massive bone defects.

Animals↗
PubMed2005

Effect of vascularity on canine distracted tibial callus consolidation.

In the consolidation period of distraction osteogenesis, mineralization occurs before corticalization. We hypothesized that the increased rate of bone mineral density correlates to the density of vascularity in the callus. We unilaterally lengthened the tibia in eight adult beagles. After a waiting period of 7 days, tibiae were lengthened for 30 days. After a consolidation period of an additional 60 days, all animals were euthanized. Just before euthanasia, blood vessels were perfused with 50% w/v barium sulfate solution, and soft radiographs of the distracted callus and the control tibiae were taken. Bone mineral density of the regenerated bones was measured preoperatively by quantitative computed tomography on Days 37, 68, and 98. Increases of the percent bone mineral density (from Day 37 to Day 98 and from Day 68 to Day 98) correlated with the blood vessel volume density ratios on Day 98. Our results suggest that preservation of the higher density of blood vessels in the consolidation period could lead to the better mineralization of the distracted callus.

Angiography↗
PubMed2005

Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system.

Osteoclasts are primary cells for physiological and pathological bone resorption, and receptor activator of nuclear factor-kappaB ligand (RANKL) is critically involved in the differentiation, activation, and survival of these cells. Recently, therapeutics for pathological bone destruction targeting RANKL pathways has attracted a great deal of attention. Herein, we review the recent advances in the research on osteoclast biology and discuss the advantages and disadvantages of anti-RANKL therapies.

Animals↗
PubMed2005

Image-guided surgery for thoracic ossification of the posterior longitudinal ligament. Technical note.

The authors describe an anterior decompression procedure for thoracic ossification of the posterior longitudinal ligament (PLL) in which they used an image guidance system in three cases. To make registration possible in anterior thoracic surgery, they devised a surgical reference frame that could be connected to a rod and attached to an external fixation device, which was then attached to the thoracic VB. The mean fiducial error at the registration was acceptable (range 0.5-0.8 mm). They were able to confirm the success of decompression on postoperative computerized tomography scans. In the removal of an ossified thoracic PLL, an image guidance system has been shown to be a useful tool.

Decompression, Surgical↗