Biomedical subjects

K Takaoka

Publications and source records attributed to K Takaoka.

At least 37 records · Page 2Linked to original sources

PubMed2001

Mutation frequencies of EXT1 and EXT2 in 43 Japanese families with hereditary multiple exostoses.

Hereditary multiple exostoses (EXT) is an autosomal dominant bone disease characterized by the formation of cartilage-capped prominences. EXT is genetically heterogeneous with at least four chromosomal loci. Among the four loci, the exostosis type 1 gene (EXT1) and type 2 gene (EXT2) have been cloned. Previous studies have shown that disease-type-specific frequency of mutations is different among various ethnic populations. To determine those frequencies in the Japanese, we conducted a large-scale mutation screening on both genes. In 23 of 43 Japanese families examined, we found 21 different mutations, of which 18 are novel. Seventeen (40%) of the 23 families had a mutation in EXT1 and six (14%) had a mutation in EXT2, suggesting that the former mutations are more frequent than the latter in Japanese EXT families. Of the 17 families with EXT1 mutations, 13 had those causing premature termination of the EXT1 protein and four showed missense mutations, whereas five of the six families with EXT2 mutations had those causing premature termination and one showed missense mutation. Interestingly, all four EXT1 missense mutations occurred in an arginine residue at codon 340 (R340) that is known as a critical site for expression of heparan sulfate glycosaminoglycans, suggesting that the region encompassing the arginine residue may play an important role in the function of the EXT1 protein. These results expand our knowledge of the ethnic difference of EXT and the structure-function relationship of the EXT genes.

DNA↗

PubMed2001

Morphological characteristics of the bony birth canal in patients with developmental dysplasia of the hip (DDH): investigation by three-dimensional CT.

We investigated the three-dimensional morphological characteristics of the pelvis in adult female patients with developmental dysplasia of the hip (DDH), using computerized tomography (CT) images. Forty-two subjects with normal hips and 40 DDH patients were recruited for the study. In the DDH group, the average transverse diameter of the pelvic inlet was significantly less and the average transverse diameter of the pelvic outlet was significantly greater than the measurements in the normal group. Further, the bony birth canal in DDH patients exhibited a higher incidence of anthropoid-type geometry, as defined by a longer sagittal diameter relative to the transverse diameter of the pelvic inlet. These findings indicate a characteristic pelvic geometry and suggest different development of the pelvis in the transverse direction in DDH patients. In addition, the obstetric conjugate length/transverse diameter of the pelvic inlet ratio was correlated to the degree of severity of acetabular dysplasia. This finding suggests that DDH is a manifestation of a developmental characteristic of the pelvis.

Adult↗

PubMed2001

Enhancement of bone morphogenetic protein-2-induced new bone formation in mice by the phosphodiesterase inhibitor pentoxifylline.

Porous collagen disks (6 mm diameter, 1 mm thickness) were impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2) (5 microg/disk) and implanted onto the back muscles of mice. Pentoxifylline (PTX), which is a methylxanthine-derived inhibitor of phosphodiesterases (PDEs), or vehicle, was injected (5, 25, 50, 100, 200, and 300 mg/kg body weight/day) into the mice subcutaneously once a day for 3 weeks from the day of implantation of the bone morphogenetic protein (BMP)-laden disks. The rhBMP-2-induced ectopic ossicles were harvested and examined using radiographic, histological, and biochemical methods to determine size, bone quality, and calcium content. When compared with controls, ossicles from mice treated with >50 mg/kg per day of PTX were significantly larger in size and had a greater calcium content. However, no differences were noted in mice treated with lower doses (5 and 25 mg/kg per day) of PTX. The temporal sequence of the bone-forming process was unchanged by PTX based on histological examination. The histology of the ossicles from high- and low-dose PTX-treated mice was essentially identical to that observed in the control mice. These experimental results indicate that PTX enhanced the bone-inducing capacity of BMP-2. The underlying mechanism of action most likely involves the inhibition of intracellular phosphodiesterases and a resulting elevation of the intracellular content of cyclic nucleotides. Further studies are warranted to understand how BMP-induced bone formation is pharmacologically modified by PTX.

Animals↗

PubMed2001

A biodegradable polymer as a cytokine delivery system for inducing bone formation.

Bone morphogenetic proteins (BMPs) that have the potential to elicit new bone in vivo have been used in a tissue-engineering approach for the repair of bone injuries and bone defects. Although it is now possible to generate large amounts of recombinant human (rh) BMPs for medical use, the major challenge remains in the development of optimal local delivery systems for these proteins. Here we describe the development of a synthetic biodegradable polymer, poly-d,l-lactic acid-p-dioxanone-polyethylene glycol block copolymer (PLA-DX-PEG). This polymer exhibits promising degradation characteristics for BMP delivery systems and good biocompatibility under test conditions. PLA-DX-PEG/rhBMP-2 composite implants induced ectopic new bone formation effectively when tested in vivo, and can repair large bone defects orthotopically. This polymeric delivery system represents an advance in the technology for the enhancement of bone repair.

Animals↗

PubMed2001

Progression of prostate cancer to neuroendocrine cell tumor.

BACKGROUND: The progression to endocrine therapy-resistant prostate cancer is partly due to clonal change to neuroendocrine cell tumor. To elucidate this pathologic process, the clinical courses of four cases of neuroendocrine cell tumor that were found at autopsy are reported. METHODS: Between 1995 and 1999, autopsies were performed for 20 cases of prostate cancer. Lesions predominantly composed of a neuroendocrine cell tumor (small cell carcinoma) were found in four men. The clinical courses of these cases were compared to 16 other non-neuroendocrine cell tumors (adenocarcinomas). RESULTS: The outstanding features of the neuroendocrine cell tumors were: (i) survival was brief after relapse, although the duration of control by employing endocrine therapy varied; (ii) the prostate-specific antigen level did not increase after relapse; and (iii) the sites of metastasis were similar to those of common adenocarcinomas. CONCLUSION: The progression to a neuroendocrine cell tumor indicated a poor prognosis and slight (if any) changes in the serum prostate-specific antigen level. This tumor might not appear to respond to any therapeutic attempt.

Aged↗

PubMed2001

Car-driving abilities of people with tetraplegia.

OBJECTIVES: To examine the relationship between the spinal cord injury (SCI) level, age, and car-driving ability in people with tetraplegia and to explore the association between car-driving ability and social activity. DESIGN: Retrospective clinical survey. SETTING: Rehabilitation center in Japan. PATIENTS: Sixty-two subjects with traumatic complete tetraplegia. INTERVENTIONS: Driving evaluation; comprehensive driver's training (muscle strengthening, transfer training, adjustment of equipment, on-road training); and questionnaire (car-driving status, employment, participation in sports). MAIN OUTCOME MEASURES: The SCI level (Zancolli's classification), age, functional status of activities of daily living (ADLs), and driving ability were obtained from the medical records. Vocational status and engagement in sports activities were investigated by questionnaire. RESULTS: The SCI level and age strongly influenced the patients' ability to drive a car independently. The highest neurologic level in which independent driving was achievable was C6A. Toilet transfer ability almost paralleled the ability to drive a car. Eighty-four percent of the people with tetraplegia who had a defined job could drive independently and 70% of the driving-independent individuals held a job. Half of driving-independent individuals participated in some sports activities. CONCLUSIONS: Toilet transfer ability is a reliable indicator for driver's training. Driving ability is an important factor that allows individuals with tetraplegia to participate in work and sports-related activities.

Activities of Daily Living↗

PubMed2001

Primary Charnley total hip arthroplasty: a comparison of American and Japanese cohorts followed for 10-20 years.

Primary Charnley total hip arthroplasties (THAs) followed for 10 to 20 years were compared between an American (183 sockets and 178 femoral prostheses) and a Japanese (145 sockets and 148 femoral prostheses) series, each performed by a single surgeon at a single hospital using similar techniques. The primary etiology was developmental dysplasia of the hip (70%) in the Japanese series and primary osteoarthrosis (50%) in the American series. Radiographic socket survival was inferior in the Japanese series at 4- to 11-year follow-up, which was attributed mainly to the etiologic difference. The American patients had higher levels of postoperative activity and developed more accelerated polyethylene wear, which may lead to an increased loosening rate of sockets > or = 10 years after THA. The American series had higher rates of femoral revision at > or = 9 years follow-up, which was attributed mainly to lower canal flare indices in that series.

Arthroplasty, Replacement, Hip↗

PubMed2001

The 'superficial' peroneal artery: a variation in cutaneous branching from the peroneal artery, nourishing the distal third of the leg.

Two different vascular patterns were encountered in cutaneous branches from the peroneal artery to the posterolateral aspect of the distal third of the leg in 22 flaps from 22 patients who underwent cutaneous or osteocutaneous peroneal flap surgery. In the type 1 vascular pattern, a branch from the peroneal artery, named the 'superficial peroneal artery', nourished the posterolateral aspect of the leg by splitting into several septocutaneous branches. In the type 2 pattern a few septocutaneous branches originated directly from the main peroneal artery and nourished the same area as that fed by the type 1 branch. The type 1 vascular pattern has not been reported to date but was seen in nine out of the 22 consecutive peroneal flaps. The superficial peroneal artery, with its considerable vascular diameter, may serve as a recipient vessel for free flaps or may serve as a donor nutrient vessel for a cutaneous flap, which can be transferred without sacrificing the main peroneal artery. Awareness of these two vascular patterns in the distal third of the leg should also help to reduce the small percentage of skin-flap failures that occur when the cutaneous or osteocutaneous peroneal flap is used.

Adult↗

PubMed2001

Evaluation of thoracic myelopathy by transcranial magnetic stimulation.

It is sometimes difficult to determine the appropriate surgical site in patients with thoracic myelopathy with diffuse or multisegmental lesions. To solve this problem, a magnetic stimulation study was carried out. Seven patients with myelopathy and 10 healthy control subjects were examined. Transcranial magnetic stimulation was applied and the motor evoked potentials (MEPs) of the intercostal muscles were recorded. The MEP latencies for the two groups were then compared. In patients with thoracic myelopathy, the MEP latencies caudal to the lesion were more extended than those of the control subjects. This method could identify the levels at which myelopathy originates in patients with a radiologically visible lesion. This method has the potential to be used for deciding the surgical site at the level responsible for myelopathy in cases with multiple or diffused compression.

Adult↗

PubMed2001

Colocalization of noggin and bone morphogenetic protein-4 during fracture healing.

The regulation of callus formation during fracture repair involves the coordinate expression of growth factors and their receptors. This article describes the temporal and spatial expression of noggin gene, an antagonist to bone morphogenetic protein (BMP), during the fracture repair process. Noggin expression was examined by means of Northern blotting and in situ hybridization and compared with the expression pattern of BMP-4 in a model of fracture repair in adult mice. Expression levels of noggin messenger RNA (mRNA) were enhanced in the early phase of fracture callus formation. The localization of the noggin mRNA was similar to that of BMP-4 mRNA. Distinct noggin mRNA signals were located predominantly in cells lining the periosteum and the cortical endosteum near the fracture site at 2 days after fracture. At 5, 10, and 21 days after fracture, noggin mRNA was detected in the chondrocytes and osteoblasts in the newly formed callus. The pattern of localization was indistinguishable from that of BMP-4. These results suggest that the noggin/BMP-4 balance could be an important factor in the regulation of callus formation during fracture healing.

Animals↗

PubMed2001

Biodegradable poly-D,L-lactic acid-polyethylene glycol block copolymers as a BMP delivery system for inducing bone.

BACKGROUND: Bone morphogenetic proteins (BMPs) are biologically active molecules capable of eliciting new bone formation. In combination with biomaterials, these proteins can be used in a clinical setting as bone-graft substitutes to promote bone repair. Collagen from animal sources has previously been the preferred carrier material in animal experiments. More recently, synthetic biodegradable polymers have been tested as a delivery vehicle for osteoinductive agents. In earlier studies performed in our laboratory, it was found that the polylactic acid homopolymers (PLA650) and poly-D,L-lactic acid-polyethylene glycol block copolymers (PLA650-PEG200) are viscous liquids that can be used as BMP delivery systems. METHODS: To obtain new PLA-PEG polymers that exhibit greater plasticity, the molecular sizes of PLA and PEG segments in the copolymer chains were increased. Plastic PLA-PEG polymers with various molecular sizes and PLA/PEG ratios were synthesized, mixed with recombinant human (rh) BMP-2, and implanted into the dorsal muscles of mice for 3 weeks to evaluate their capacity to elicit new bone formation. To compare the plastic PLA-PEG polymer with the liquid PLA650-PEG200 polymer, these two polymers were combined with rhBMP-2, implanted, and harvested after 3 weeks. Bone mineral content (BMC), bone area, and bone mineral density (BMD) of the ectopic new bone were measured by means of single energy X-ray absorptiometry (SXA). RESULTS: All of the PLA6,500-PEG3,000 implants with 10 or 20 microg of rhBMP-2 showed new bone formation. In contrast, little or no bone formation was seen in other plastic PLA-PEG implants with rhBMP-2. Control implants that lacked rhBMP-2 did not show new bone formation. Radiographic and histologic examinations showed that the PLA6,500-PEG3,000 implants with rhBMP-2 harvested 3 weeks after implantation had normal bone characteristics with hematopoietic marrow and osseous trabeculae. SXA analysis showed that the values for bone mineral content (BMC), bone area, and bone mineral density (BMD) of new bone resulting from the use of plastic PLA6,500-PEG3,000 polymers with rhBMP-2 were significantly higher than those obtained with the liquid PLA650-PEG200 polymers (p < 0.001 for each of the three values). CONCLUSIONS: These results indicate that the PLA6,500-PEG3000 block copolymer with plastic properties works effectively as a BMP delivery system. These data suggest that the total molecular size and ratio of PLA size to PEG size is an essential factor in determining the efficacy of a BMP delivery system. After implantation, it is possible that the PLA6,500-PEG3,000 pellets might have absorbed tissue fluids and become swollen, resulting in bone formation that exceeded the size of the original implants. This expansion characteristic is a potentially beneficial property, given the intended practical application of the polymer in the repair of bone defects. CLINICAL RELEVANCE: New synthetic biodegradable delivery systems will play an important role in the clinical applications of rhBMPs in which local formation of bone via an osteoinductive graft material is needed. Further pre-clinical and clinical work is necessary to establish the safety of these implants before they are adopted for widespread clinical use.

Animals↗

PubMed2000

Sound velocity measurements of nuclear-ordered solid 3He along the melting curve.

We have measured the temperature dependence of the 10.98 MHz longitudinal sound velocity of solid 3He in the nuclear-ordered U2D2 phase and in the paramagnetic phase along the melting curve. The temperature dependence of the sound was attributed to the contributions from the nuclear spin system and the molar volume change along the melting curve. The sound velocity increased with temperature as T4 in the U2D2 phase and the sound anisotropy due to the exchange interaction was found to be about 10% among single-domain crystals investigated. The average value of the Gruneisen constant of the spin wave velocity in the ordered phase was gamma(c) = 16 and is compared to the calculated value of the multiple-exchange model.

Journal Article↗

PubMed2000

Poor bone quality or hip structure as risk factors affecting survival of total-hip arthroplasty.

BACKGROUND: The principal long-term complication after total hip arthroplasty (THA) has been aseptic fixation failure. Many hip prostheses and operative techniques have been developed to improve outcomes, but few measures have been taken to cope with poor bone quality or hip structure. We assessed risk factors for aseptic fixation failure after THA. METHODS: We assessed, by multivariate analysis, survival of 405 primary Charnley THAs to identify risk factors for aseptic fixation failures. We also investigated risk factors for development of rapid polyethylene wear (penetration depth of the femoral head into the socket polyethylene > or = 2 mm/year) FINDINGS: In the entire series of 405 THAs, with use of radiographic fixation failure or revision for a loose socket as the endpoint, development of rapid polyethylene wear and the preoperative diagnosis of atrophic osteoarthrosis (defined by scarce osteophyte formation) were identified as risk factors for socket loosening (p < or = 0.02). A medullary canal with an unfavourable geometry (a stovepipe canal, Noble's canal-flare index < 3.0) was the only risk factor for femoral fixation failure (p < or = 6.7x10(3)). The only variable related to development of rapid polyethylene wear was the type of steel used in the femoral prosthesis--Ortron 90 prostheses significantly lowered the rate of development of rapid wear from 12.7% to 0.4%. In the 248 THAs in which these femoral prostheses were used, socket survival was affected only by the preoperative diagnosis of atrophic osteoarthrosis (for radiographic fixation failure and revision, p=4.0x10(-5) and p=0.042, respectively). INTERPRETATION: In THA, the critical risk factors are poor bone quality, which manifests as atrophic osteoarthrosis, for socket survival and poor bone structure for femoral-prosthesis survival. To ensure longer durability of THAs, these factors should be assessed further and efforts, especially biological initiatives, should be made to resolve them.

Arthroplasty, Replacement, Hip↗

PubMed2000

A new system for the anterior restoration and fixation of thoracic spinal deformities using an endoscopic approach.

STUDY DESIGN: A report on the results of animal experiments in which the authors' new system that enables the anterior correction and fixation of thoracic spinal deformity by use of a thoracic endoscope and small incisions was used. The results suggest that the new approach involving thoracoscopic anterior correction and fusion for thoracic spinal deformity could be adapted successfully for the clinic. OBJECTIVE: To develop a new system that enables the anterior correction and fixation of thoracic spinal deformity by use of a thoracic endoscope and small incisions. SUMMARY OF BACKGROUND DATA: Anterior correction and fusion through open thoracotomy have been applied mainly for thoracic scoliosis because this approach provides effective correction with short fusion. However, excellent visualization of the spine during thoracic surgical procedures led to the development of thoracoscopic spine surgery. Therefore, the authors postulated that a thoracoscopic approach could allow not only discectomy but also correction and fusion of the deformed thoracic spine in a single surgical event. METHODS: The vertebral columns and attached thoracic walls were dissected from fresh porcine cadavers and used in the experimental surgery to evaluate the new system. As a next step, thoracoscopic surgery using this new system was performed on four or five vertebrae of five live pigs with an average weight of 50 kg. Initially, the discs and rib heads were removed through the thoracic wall. For each vertebra, a screw connected to a shaft used as a screw holder was inserted through the thoracic wall in a posterior to anterior direction. Each shaft then was linked outside the body to an outrigger. This outrigger was used to both create and restore scoliosis. A rod then was introduced through the thoracic wall and fixed to the screw heads. RESULTS: The animal experiments clearly showed that it was possible to change the Cobb angles of the spine through the use of the outrigger apparatus. In cadaver experiments, it was possible to create scoliosis and re-store it by 25 degrees to 35 degrees. Also, surgery on live pigs resulted in scoliosis of approximately 30 degrees, which means approximately 5 degrees to 10 degrees for each disc space. The procedures used also demonstrated that it was possible to fix a rod, introduced into the pleural cavity through a port, with screw heads. CONCLUSIONS: The use of this system successfully changed the Cobb angle of the spine, which suggests that its use should make it possible to correct spinal deformities. This apparatus also succeeded in fixing the rods in the screw heads, which raises the possibility of its use in spinal fixation. The authors believe that this apparatus could be adapted successfully for clinical use. Studies currently are under way in clinics using the new system.

Animals↗

PubMed2000

Comparison of the risk factors for coronary artery spasm with those for organic stenosis in a Japanese population: role of cigarette smoking.

We compared the risk factors for coronary spasm with those for coronary atherosclerosis in 183 patients with coronary spasm, 132 patients with coronary organic stenosis, and 224 control subjects with chest pain syndrome. Our findings confirmed that, when compared with controls, age, gender, total cholesterol, LDL-cholesterol, hypertension, diabetes mellitus, and cigarette smoking are all significant risk factors for coronary organic stenosis. On the other hand, only cigarette smoking proved to be a significant risk factor for coronary spasm. Also, when compared between coronary spasm group and coronary organic stenosis group, the incidence of cigarette smoking in males was significantly higher in the coronary spasm group than in the coronary organic stenosis group. We conclude that cigarette smoking is a crucial risk factor for coronary spasm. On the other hand, serum lipid levels and the incidence of hypertension and diabetes mellitus were within the normal ranges in the coronary spasm patients and were thus poorly associated with coronary spasm. These results showed that the risk factors for coronary spasm differ significantly from those for atherosclerosis-based coronary stenosis in the Japanese. Among the risk factors for coronary atherosclerosis (organic stenosis) smoking alone was a significant preventable risk factor for coronary artery spasm.

Aged↗

PubMed2000

Multiple telescoping anastomosis on an artery.

The telescoping anastomotic technique was carried out four times on the rat femoral artery in order to examine whether the technique could safely be used three to four times for repair of an artery that was injured at two different sites. In addition, the technique was repeated five and six times to determine the maximum number of anastomosis that could be performed on an artery and to clarify problems of the telescoping anastomosis. In the rats in which the anastomosis was carried out four and five times, 100% patency was obtained, while the first occlusion occurred in a graft on which the anastomosis was repeated six times. The telescoping technique appeared to safely be used three or four times for repair of an artery that had been divided at two sites if tension of the repaired vessel was kept low by the grafting, and torsion of the graft and deformities of the inserted vessel were minimal.

Animals↗

PubMed2000

Ectopic calcification following tibial fracture: property analysis.

We present a patient whose ectopic calcification following deep posterior compartment syndrome was studied by electron microscopy, chemical analyses, and X-ray diffraction. The patient complained of a toe flexion deformity following a tibial fracture which he sustained 18 years earlier. Damage to the peroneal artery was demonstrated by magnetic resonance angiography, suggesting that the patient had had deep posterior compartment syndrome in the past. A large radiopaque mass, identified in the flexor hallucis longus muscle by radiographs and computed tomography, was resected, resulting in a dramatic improvement of the toe deformity. The resected material was analyzed in detail. It included no osseous tissue, and was not birefringent under a polarizing microscope, being compatible with ectopic calcification rather than ossification. On electron microscopy the material was found to be an assembly of tiny rods. Chemical and X-ray diffraction analyses suggested a carbonate-containing apatite as the most probable substance.

Adult↗

PubMed2000

Characterization of functional endothelin receptors in the porcine myometrium.

To characterize the endothelin (ET) receptor that mediates the contraction induced by ET-1 in the porcine myometrium, we carried out a contraction study, radioligand binding study and molecular study (reverse transcription polymerase chain reaction) for detection of ET receptor-coding genes (mRNA). ET-1 (1 nM-1 microM) caused a tetrodotoxin-insensitive contraction in both longitudinal and circular muscles, but the longitudinal muscle was more sensitive to ET-1 than was the circular muscle. On the other hand, ET-3 and sarafotoxin S6c were less effective to cause a contractile response. The contraction induced by ET-1 was markedly inhibited by BQ123 and FR139317, but BQ788 only slightly inhibited the response induced by ET-1. The radioligand binding study indicated the presence of a single class of 125I-ET-1 binding sites with the same Kd value in both muscle layers. However, Bmax in the longitudinal muscle (3252 fmol/mg protein) was significantly higher than that in the circular muscle (1883 fmol/mg protein). ET-1 and FR139317 inhibited the specific 125I-ET-1 binding completely, but ET-3, sarafotoxin S6c and BQ3020 only slightly inhibited the specific binding (inhibition, 10-20%), suggesting that ET(A) is the dominant ET receptor subtype in the porcine myometrium. The results of the molecular study indicated the expression of both ET(A) and ET(B) receptor-coding genes in the porcine myometrium. In conclusion, ET-1 causes contraction of the porcine myometrium through activation of the ET(A) receptor present on smooth muscle cells. There is a marked muscle layer-related difference (longitudinal muscle > circular muscle) in the ET-1-induced contraction and the ET(A) receptor concentration.

Animals↗