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Biomedical subjects

Kozo Nakamura

Publications and source records attributed to Kozo Nakamura.

At least 145 records · Page 8Linked to original sources
PubMed2002

RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta.

Osteoclasts are cells of monocyte/macrophage origin that erode bone matrix: regulation of their differentiation is central to the understanding of the pathogenesis and treatment of bone diseases such as osteoporosis. Signalling by RANKL (receptor activator of NF-kappaB ligand), also known as Tnfsf11, is essential for the induction of osteoclast differentiation, and it must be strictly regulated to maintain bone homeostasis. But it is not known whether RANKL signalling to the cell interior is linked to any regulatory mechanisms. Here we show that RANKL induces the interferon-beta (IFN-beta) gene in osteoclast precursor cells, and that IFN-beta inhibits the differentiation by interfering with the RANKL-induced expression of c-Fos, an essential transcription factor for the formation of osteoclasts. This IFN-beta gene induction mechanism is distinct from that induced by virus, and is dependent on c-Fos itself. Thus an autoregulatory mechanism operates-the RANKL-induced c-Fos induces its own inhibitor. The importance of this regulatory mechanism for bone homeostasis is emphasized by the observation that mice deficient in IFN-beta signalling exhibit severe osteopenia (loss of bone mass) accompanied by enhanced osteoclastogenesis. Our study places the IFN-beta system in a new context, and may offer a molecular basis for the treatment of bone diseases.

Animals↗
PubMed2002

Computer-assisted anterior spinal surgery for a case of recurrent giant cell tumor.

A computer-assisted image guidance system has recently been used for posterior spinal surgery. We applied this system to anterior revision surgery of the cervicothoracic junction for a patient with recurrent thoracic spinal giant cell tumor. Anterior computer-assisted spinal surgery was achieved by attaching reference markers to threaded pins inserted into a vertebral body. The locations of anatomic structures in the surgical field of this patient were difficult to identify because of previous surgery. Both accurate resection of the tumor and anterior fusion with iliac bone autograft between C6 and T3 were successfully performed using a computer-assisted image guidance system. This system is useful for anterior spinal surgery because it enables a surgeon to perform safe and accurate surgery.

Adult↗
PubMed2002

Bipolar revision arthroplasty for failed threaded acetabular components: radiographic evaluation of cup migration.

We studied the radiographic results of bipolar revision hip arthroplasty in 25 patients (25 hips). These patients had suffered from osteoarthrosis of the hip due to acetabular dysplasia and had undergone total hip replacement using smooth threaded acetabular components. In the revision surgery, these components were replaced by bipolar cups; autografts were implanted in 23 patients and hydroxyapatite grains were added in 7. At the time of follow-up, the severity of migration was radiographically graded from I to IV: grade I, 5 mm or less; grade II, 6 to 10 mm; grade III, 11 to 15 mm; and grade IV, 16 mm or more. Five to 11 years (average, 7.0 years) after surgery, 9 patients were classified as grade I, 6 as grade II, 4 as grade III, and 6 as grade IV. Among the 6 individuals with grade IV migration, hydroxyapatite grains had been used in 5. There was a significant negative correlation between the distance of migration and the increase in size of the threaded acetabular components used in the primary total hip replacement and the bipolar cups in the revision surgery. Because of the tendency to migrate, we concluded that this procedure has a limited role in revision surgery.

Acetabulum↗
PubMed2002

Juxtacortical osteoma of the ulna.

Acase of juxtacortical osteoma of the ulna in a 47-year-old woman is presented. She had a dense bony mass on the ulna. Radiological examinations (plain radiography, computed tomography, magnetic resonance imaging) strongly suggested a rare case of juxtacortical osteoma of a long tubular bone. The differential diagnosis included parosteal osteosarcoma, melorheostosis, osteochondroma, end-stage juxtacortical myositis ossificans, and fibrous dysplasia protuberans. The tumor was excised totally for thorough pathological examination, which revealed it to be composed of lamellar bone, suggesting that the origin was periosteal.

Biopsy, Needle↗
PubMed2002

Nonself-centering Bateman bipolar endoprosthesis for nontraumatic osteonecrosis of the femoral head: a 12- to 18-year follow-up study.

We studied the long-term results of bipolar endoprosthetic replacement in 12 patients (12 hips) 12 to 18 years after surgery. These patients had Ficat stage III nontraumatic osteonecrosis of the femoral head. The original Bateman universal proximal femoral endoprosthesis, which did not have a self-centering mechanism, was inserted without cement as a primary surgical intervention. Three patients underwent revision surgery, 3, 17, and 17 years after surgery, respectively. The reasons for revision surgery were migration of the stem in 2 patients and migration of both the stem and the outer cup in 1. In the remaining 9 patients, the total Merle d'Aubigné and Postel score was 16.1 +/-1.3 at the time of follow-up. Radiographs showed migration of the endoprosthesis in 1 of these 9 patients. Thus, 11 of the 12 patients retained the endoprosthesis 12 years or more after implantation. We concluded that the original Bateman endoprosthesis was effective in delaying the need for total hip replacement for more than 10 years in patients with Ficat stage III nontraumatic osteonecrosis of the femoral head.

Adult↗
PubMed2002

Iliac bone graft for steroid-associated osteonecrosis of the femoral condyle.

The use of steroid medication may predispose to osteonecrosis of the femoral condyle. However, there is a controversy regarding treatment of this disease, especially for lesions in advanced stages. Since 1987, the authors have treated such lesions by autologous osteoperiosteal graft obtained from the iliac bone. When limb alignment was affected by the disease, proximal tibial valgus or varus osteotomy was done concomitantly. The rationale for this method is to replace the necrotic bone and damaged cartilage by autogenous bone and periosteum, anticipating the chondrogenic potential of the latter. In this study, 10 knees in eight patients were reviewed to learn the outcome of this procedure with a mean followup of 79 months (range, 32-158 months). The grafts were incorporated successfully in nine joints, and satisfactory results were achieved in all patients. Therefore autologous iliac bone graft is a promising alternative for treatment of osteonecrosis, especially when patients are young and physically active.

Adolescent↗
PubMed2002

Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease that causes paralysis by compressing the spinal cord. Based on the fact that the nucleotide pyrophosphatase (Npps) gene is responsible for ectopic ossification in ttw, an OPLL model mouse, the possibility was explored whether the human NPPS gene is associated with susceptibility to and severity of OPLL. First, we screened for single-nucleotide polymorphisms (SNPs) in the human NPPS locus using selected 25 OPLL patients with young onset (< 35 years old) or severe ossification (> 10 ossified vertebrae), and identified three novel SNPs in the locus. A case-control association study between 180 OPLL patients and 265 non-OPLL controls showed that one of these SNPs, IVS15-14T --> C substitution, was more frequently observed in OPLL patients (p = 0.022), especially in those with severe ossification (p < 0.0001) and young onset (p = 0.002), than in controls. A stratified study with the number of ossified vertebrae in OPLL patients revealed that IVS15-14T --> C substitution (p = 0.013) as well as young onset (p = 0.046) and female sex (p = 0.006) were associated with severe ossification. We conclude that the IVS15-14T --> C substitution in the human NPPS gene is associated not only with susceptibility to, but also with severity of OPLL.

Adult↗
PubMed2002

Klotho gene polymorphisms associated with bone density of aged postmenopausal women.

Because mice deficient in klotho gene expression exhibit multiple aging phenotypes including osteopenia, we explored the possibility that the klotho gene may contribute to age-related bone loss in humans by examining the association between klotho gene polymorphisms and bone density in two genetically distinct racial populations: the white and the Japanese. Screening of single-nucleotide polymorphisms (SNPs) in the human klotho gene identified 11 polymorphisms, and three of them were common in both populations. Associations of the common SNPs with bone density were investigated in populations of 1187 white women and of 215 Japanese postmenopausal women. In the white population, one in the promoter region (G-395A, p = 0.001) and one in exon 4 (C1818T, p = 0.010) and their haplotypes (p < 0.0001) were significantly associated with bone density in aged postmenopausal women (> or = 65 years), but not in premenopausal or younger postmenopausal women. These associations were also seen in Japanese postmenopausal women. An electrophoretic mobility shift analysis revealed that the G-A substitution in the promoter region affected DNA-protein interaction in cultured human kidney 293 cells. These results indicate that the klotho gene may be involved in the pathophysiology of bone loss with aging in humans.

Aged↗
PubMed2002

Strong static magnetic field stimulates bone formation to a definite orientation in vitro and in vivo.

The induction of bone formation to an intentional orientation is a potentially viable clinical treatment for bone disorders. Among the many chemical and physical factors, a static magnetic field (SMF) of tesla order can regulate the shapes of blood cells and matrix fibers. This study investigated the effects of a strong SMF (8 T) on bone formation in both in vivo and in vitro systems. After 60 h of exposure to the SMF, cultured mouse osteoblastic MC3T3-E1 cells were transformed to rodlike shapes and were orientated in the direction parallel to the magnetic field. Although this strong SMF exposure did not affect cell proliferation, it up-regulated cell differentiation and matrix synthesis as determined by ALP and alizarin red stainings, respectively. The SMF also stimulated ectopic bone formation in and around subcutaneously implanted bone morphogenetic protein (BMP) 2-containing pellets in mice, in which the orientation of bone formation was parallel to the magnetic field. It is concluded that a strong SMF has the potency not only to stimulate bone formation, but also to regulate its orientation in both in vitro and in vivo models. This is the first study to show the regulation of the orientation of adherent cells by a magnetic field. We propose that the combination of a strong SMF and a potent osteogenic agent such as BMP possibly may lead to an effective treatment of bone fractures and defects.

Alkaline Phosphatase↗
PubMed2002

Possible involvement of IkappaB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor kappaB ligand.

Recent studies have revealed the essential role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) in osteoclast differentiation and activation. Adenovirus vector could efficiently transduce genes into RAW264.7 cells, which differentiate into osteoclast-like multinucleated cells in the presence of RANKL. The role of NF-kappaB and c-jun N-terminal kinase (JNK) activation in RANKL-induced osteoclast differentiation was investigated using an adenovirus vector carrying the dominant negative 1kappaB kinase 2 gene (AxIKK2DN) or dominant negative MKK7 gene (AxMKK7DN). IKK2DN and MKK7DN overexpression in RAW cells specifically suppressed the NF-kappaB activation and JNK activation in response to RANKL, respectively, without affecting other signaling pathways. Either inhibition of NF-kappaB or JNK pathways dose-dependently inhibited osteoclast formation induced by RANKL. These results suggest that both NF-kappaB and JNK activation are independently required for osteoclast differentiation.

Adenoviridae↗
PubMed2002

Association analysis of single nucleotide polymorphisms in cartilage-specific collagen genes with knee and hip osteoarthritis in the Japanese population.

Osteoarthritis (OA) is one of the most common diseases in the elderly. Although its pathophysiology is complex and its molecular basis remains to be determined, much evidence suggests that OA has strong genetic determinants. To search for susceptibility loci of OA, we selected seven candidate genes encoding cartilage-specific collagens (type II, IX, X, and XI collagens) and performed association analysis for OA using single nucleotide polymorphisms (SNPs) in the coding region of these genes. Four hundred seventeen OA samples and 280 control samples were collected from the Japanese population, and 12 SNPs were genotyped. Our studies have identified two susceptibility loci of OA: COL2A1 and COL9A3. An SNP in COL9A3 showed significant association with knee OA (p = 0.002, odds ratio [OR] = 1.48). Haplotype analysis showed significant association between a specific haplotype of COL2A1 and hip OA (p = 0.024; OR = 1.30). Further analysis of these two genes will shed light on the molecular mechanisms of OA.

Aged↗
PubMed2002

[A case of SAPHO syndrome with paraplegia due to a thoracic kyphosis].

A 63-year-old man visited our hospital in January 1993 because of back pain, which had been present for a year and persisted. The patient was diagnosed compression fracture of thoracic spine by another hospital. Thoracic plain radiographs revealed destructive and sclerotic changes with reduction of height of T 8, T 9 vertebral body. He had kyphosis on this level. Radiographs of the chest revealed hyperostosis of bilateral proximal clavicle. We diagnosed SAPHO syndrome (synovitis, acne, pustlosis, hyperostosis, and osteomyelitis: SAPHO) with T 8, T 9 spondylodiscitis, however without any skin manifestations. Oral indomethacin was effective, however thoracic kyphosis progressed gradually. Spastic gait and paraplegia appeared from February 1998, at last on July he was unable to walk independently. MRI showed the compression of spinal cord on T 8, T 9 level. We performed circumferential decompression and fusion with instrumentation. His paraplegia improved after surgery. We describe a rare case of SAPHO syndrome with paraplegia due to a thoracic kyphosis.

Acquired Hyperostosis Syndrome↗
PubMed2002

Monitoring of side shift exercise using an electromagnetic three-dimensional measuring device.

In order to investigate the usefulness of an electromagnetic three-dimensional measuring device as a monitor for the side shift exercise, the evaluation by the well-trained physical therapist as to whether the exercise was properly performed or not was compared with the evaluation using data obtained by the device. The side shift exercises performed by twenty-four female patients with idiopathic scoliosis were classified as "good," "rotation," or "bend" by the well-trained physical therapist. By the use of the data obtained by the electromagnetic three-dimensional measuring device, whether the exercise was "rotation" or not could be predicted with 100% sensitivity and 100% specificity, and whether the exercise was "bend" or not could be predicted with 83% sensitivity and 100% specificity. These results suggested that the electromagnetic three-dimensional measuring device could be a useful monitor for the side shift exercise.

Adolescent↗
PubMed2001

Regulation of osteoblast, chondrocyte, and osteoclast functions by fibroblast growth factor (FGF)-18 in comparison with FGF-2 and FGF-10.

This study investigated the actions of fibroblast growth factor (FGF)-18, a novel member of the FGF family, on osteoblasts, chondrocytes, and osteoclasts and compared them with those of FGF-2 and FGF-10. FGF-18 stimulated the proliferation of cultured mouse primary osteoblasts, osteoblastic MC3T3-E1 cells, primary chondrocytes, and prechondrocytic ATDC5 cells, although it inhibited the differentiation and matrix synthesis of these cells. FGF-18 up-regulated the phosphorylation of extracellular signal-regulated kinase in both osteoblasts and chondrocytes and up-regulated the phosphorylation of p38 mitogen-activated protein kinase only in chondrocytes. FGF-18 mitogenic actions were blocked by a specific inhibitor of extracellular signal-regulated kinase in both osteoblasts and chondrocytes and by a specific inhibitor of p38 mitogen-activated protein kinase in chondrocytes. With regard to the action of FGF-18 on bone resorption, FGF-18 not only induced osteoclast formation through receptor activator of nuclear factor-kappaB ligand and cyclooxygenase-2 but also stimulated osteoclast function to form resorbed pits on a dentine slice in the mouse coculture system. All these effects of FGF-18 bore a close resemblance to those of FGF-2, whereas FGF-10 affects none of these cells. FGF-18 may therefore compensate for the action of FGF-2 on bone and cartilage.

Animals↗
PubMedDate not supplied

Evaluation by fluorescence resonance energy transfer of the stability of nonviral gene delivery vectors under physiological conditions.

The stability in physiological medium of polyplex- and lipoplex-type nonviral gene vectors was evaluated by detecting the conformational change of complexed plasmid DNA (pDNA) labeled simultaneously with fluorescein (energy donor) and X-rhodamine (energy acceptor) through fluorescence resonance energy transfer (FRET). Upon mixing with cationic components, such as LipofectAMINE, poly(L-lysine), and poly(ethylene glycol)-poly(L-lysine) block copolymer (PEG-PLys), the fluorescence spectrum of doubly labeled pDNA underwent a drastic change due to the occurrence of FRET between the donor-acceptor pair on pDNA taking a globular conformation (condensed state) through complexation. The measurement was carried out also in the presence of 20% serum, under which conditions FRET from condensed pDNA was clearly monitored without interference from coexisting components in the medium, allowing evaluation of the condensed state of pDNA in nonviral gene vectors under physiological conditions. Serum addition immediately induced a sharp decrease in FRET for the LipofectAMINE/pDNA (lipoplex) system, which was consistent with the sharp decrease in the transfection efficiency of the lipoplex system in serum-containing medium. In contrast, the PEG-PLys/pDNA polyplex (polyion complex micelle) system maintained appreciable transfection efficiency even in serum-containing medium, and FRET efficiency remained constant for up to 12 h, indicating the high stability of the polyion complex micelle under physiological conditions.

Cell Line↗
PubMedDate not supplied

Conservative treatment for adolescent idiopathic scoliosis: can it reduce the incidence of surgical treatment?

Since 1986, the authors have been conducting conservative treatment for idiopathic scoliosis with the combination of brace treatment and physical treatment (side shift exercise and hitch exercise). A total of 328 female patients with adolescent idiopathic scoliosis who were at least 10 years of age at the first visit, with Cobb angle of 10 degrees at the minimum and followed until after 15 years of age or skeletal maturity were included. The average Cobb angle was 32.4 degrees and the average age was 13.8 years at the first visit. Surgery was recommended when curvature progressed to >50 degrees. Twenty of 328 patients (6.1%) with more severe curves to begin with (mean Cobb angle at admission of 48.5 +/- 9.3 degrees ) progressed to 62.2 +/- 8.5 degrees and were treated with spinal fusion by the age of 16.0 +/- 2.6 years. The remaining 308 patients, of comparable age at inception of treatment but with a smaller original mean Cobb angle (32.4 +/- 11.1 degrees ), showed no significant increase in magnitude of curvature (mean 33.6 +/- 11.5 degrees ) by the time of discharge (18.6 +/- 3.1 years). The fact that curvature magnitude was maintained at <35 degrees means that these patients will have a good prognosis for avoiding dramatic progression during adulthood.

Adolescent↗
PubMedDate not supplied

A unique mechanism of giving way of the knee after tibial plateau fracture.

This report describes a patient with a 31-month-old previously operated tibial plateau fracture who had frequent giving way of the involved knee. The symptoms and physical examination suggested a meniscus injury, which was finally ruled out by arthroscopy. Magnetic resonance imaging (MRI) in dynamic knee positions was then done, which showed that a bone ridge on the articular surface caused the symptoms by interfering with the lateral meniscus. The ridge was removed arthroscopically, and a satisfactory result was obtained.

Arthroscopes↗