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Biomedical subjects

K Takaoka

Publications and source records attributed to K Takaoka.

At least 55 records · Page 3Linked to original sources
PubMed2000

Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice.

The administration of either Pentoxifylline (PTX), a methylxanthine derivative and an inhibitor of cyclic AMP (c-AMP) phosphodiesterases (PDEs), or Rolipram, an inhibitor specific to type-4 PDE (PDE4) in normal mice, significantly increased both cortical and cancellous bone mass. Vertebrae and tibiae from mice treated with PTX or Rolipram were analyzed by means of bone densitometry and histomorphometry. The results revealed that both PTX and Rolipram increased bone mass in normal mice mainly through the acceleration of bone formation. These findings suggest that both PTX and Rolipram can enhance physiological bone formation and thereby increase bone mass in normal mice. The possibility that these agents may be of value for the treatment of osteoporosis is discussed.

Absorptiometry, Photon↗
PubMed2000

Expression of bone morphogenetic protein and its receptors in osteosarcoma and malignant fibrous histiocytoma.

BACKGROUND: Bone morphogenetic protein (BMP) activity has been found in cases of malignant fibrous histiocytoma (MFH) and osteosarcoma but only tumors in the latter category show evidence of ossification. The aim of this study was to try to understand this difference by examination of the distribution of BMP and its receptors (BMPR) for this bone inducing protein in these tumors. METHODS: Sections of 11 osteosarcoma and 10 MFH were analyzed immunohistochemically for BMP and BMPRs by use of the avidin-biotin peroxidase method. RESULTS: Nine out of 11 osteosarcoma cases (80.1%) showed positive staining for both BMP and BMPRs. Two cases of chondroblastic type osteosarcoma did not show any significant staining for BMP and BMPRs. In eight out of 10 MFH cases (80%) there was positive staining for BMP. No immunoreactivity for BMPRs was found in any case of MFH. CONCLUSIONS: MFH does not express BMPRs and this may be the reason why-MFH tumors do not ossify, even in the presence of BMP.

Bone Morphogenetic Proteins↗
PubMed2000

Cervical pedicle screw insertion: assessment of safety and accuracy with computer-assisted image guidance.

We used a commercially available computer-assisted image-guidance system for cervical pedicle screw insertion in both the laboratory and in a preliminary clinical setting. Nine plastic cervical spine models (C2-C7) were used in the laboratory test. The StealthStation was used to create the preoperative plan for each screw such that it would be inserted down the center of the pedicle, parallel to the long axis. Using a light-emitting diode-equipped drill guide, 2-mm holes were drilled in 108 pedicles. A total of 108 pedicle holes were drilled. The mean trajectory deviation from the surgical plan in the axial plane was 1.7+/-1.7 degrees (range, 0 to 8 degrees), and the mean deviation of the position of the hole was 1.7+/-0.6 mm (range, 0.1 to 2.9 mm). Eighty-three drill holes (76.9%) were contained within the pedicles, whereas partial cortical perforation was noted in 25 pedicles (23.1%). In the clinical setting, 36 cervical pedicle screws were inserted in nine patients using the image-guided system. Within the limits of imaging artifact, all 36 pedicle screws appear to have been inserted accurately by postoperative computed tomographic examination. No neurologic or vascular complications were encountered.

Aged↗
PubMed2000

Thoracic epidural desmoplastic fibroma.

Desmoplastic fibroma is a relatively uncommon tumor and rarely involves the spine. The authors describe a 20-year-old woman with a thoracic epidural desmoplastic fibroma treated by complete resection and posterior spinal fusion. Four years after surgery, neither the tumor nor clinical symptoms have recurred. Thus, complete resection is considered necessary to treat this tumor.

Adult↗
PubMed2000

Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice.

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.

Animals↗
PubMed1999

The E-Box motif, recognized by tissue-specific nuclear factor(s), is important for BMP-4 gene expression in osteogenic cells.

We analyzed the promoter activity of mouse BMP-4 gene in three different types of cell lines and demonstrated that position -786 to -691 of the 5'-flanking region of exon I plays a critical role for regulation of tissue specific expression of mouse BMP-4 gene in cells of an osteogenic lineage. By use of site-directed mutagenesis, we have established that the E-box, CATCTG, located within this 5'-flanking region, is essential for tissue-specific transcriptional activation of mouse BMP-4 gene and demonstrated that an osteogenic lineage-specific novel transcriptional factor(s) recognizes this E-box.

Animals↗
PubMed1999

Experimental spinal fusion with use of recombinant human bone morphogenetic protein 2.

STUDY DESIGN: Posterolateral lumbar spinal fusion with use of recombinant human bone morphogenetic protein 2 (rhBMP-2) was tested in rabbits by implanting composites of rhBMP-2 and collagen carrier. OBJECTIVES: To examine the bone-formation-inducing activity of rhBMP-2 and find the optimal amount of rhBMP to add to a collagen carrier to constitute bone-formation-inducing implants to be substituted for bone graft in posterolateral spinal fusion in rabbits. SUMMARY OF BACKGROUND DATA: In animal models, rhBMP-2--impregnated collagen has been successfully used for posterolateral spinal fusion, indicating that it is a potential substitute for the autogenous corticocancellous bone graft currently used most routinely in posterolateral lumbar spinal fusion. METHODS: Nine rabbits were divided into three equal groups. The bilateral L4-L5 transverse processes were exposed, and collagen strips impregnated with rhBMP-2 (10, 50, or 200 micrograms) were placed on the left transverse processes, and collagen strips alone were inserted on the right. All rabbits were killed 24 weeks after surgery. The implanted sites were assessed for new bone formation and bony fusion by radiography and histologic examination. RESULTS: New bone formation was noted in intertransverse spaces on the left side of all rabbits except one (10 micrograms rhBMP-2). Twelve weeks after implantation, no new bone formation was seen on the right side of all animals. The newly formed bone masses were significantly larger in the 50-microgram and 200-microgram rhBMP-2 groups than in the 10-microgram rhBMP-2 group (P < 0.01), but there was no significant difference between bone formation in the 50-microgram and 200-microgram groups (P = 0.647). CONCLUSIONS: The rhBMP-2/collagen composite implant was an effective bone graft substitute for achieving posterolateral spinal fusion. When combined with a collagen carrier, the optimal rhBMP-2 dose for achieving posterolateral spinal fusion seemed to be approximately 50 micrograms per segment in rabbits.

Animals↗
PubMed1999

New synthetic absorbable polymers as BMP carriers: plastic properties of poly-D,L-lactic acid-polyethylene glycol block copolymers.

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. To find new synthetic absorbable polymers with plastic nature that can be used as BMP-carrier materials, six types of poly-D,L-lactic acid-polyethylene glycol block copolymer (PLA-PEG) with various molecular weights of PLA and PEG were synthesized. These were PLA6, 500-PEG3,000 (P-1), PLA11,500-PEG3,000 (P-2), PLA17,500-PEG3,000 (P-3), PLA6,500-PEG1,000 (P-4), PLA15,000-PEG8,000 (P-5), and PLA8, 500-PEG1,000 (P-6). Fifty milligrams of these polymers was mixed with 0 microg (control) or 5, 10, or 20 microg of recombinant human BMP-2 (rhBMP-2). These pellets were implanted into the dorsal muscle pouches of 144 mice (six pellets consisting of the same polymer and dose of rhBMP-2 for a specific group). Three weeks after surgery, the pellets were harvested and examined by radiographic and histological methods. All P-1 pellets with 10 or 20 microg of rhBMP-2 showed bone formation with hematopoietic marrow and bony trabeculae, as did one third of those with 5 microg of rhBMP-2. The incidence of new bone formation with P-2 pellets or that of P-5 pellets was lower than that of P-1 pellets. No bone was formed in any other type of pellet. These results indicated that the PLA6, 500-PEG3,000 polymer with plastic properties was found to work well as a BMP carrier.

Absorption↗
PubMed1999

Long-term result of arterial grafts interposed for arterial defects using the telescoping anastomotic technique: histological and angiographic study.

The arterial grafting model for arterial defects provides an ideal environment for the microvascular telescoping anastomosis because tension of the repaired vessel is maintained low and deformities of the inserted vessel end is minimal due to the thick arterial wall. The left femoral artery was grafted in 46 rats into the defect created in the right femoral artery using the telescoping anastomotic technique at both the proximal and distal anastomoses. The grafts were seen histologically and angiographically 3 to 4 months postoperatively in order to fairly evaluate the telescoping anastomosis in terms of long-term patency, stenosis, and changes in the outer and inner walls at the anastomosis. All arterial grafts were patent 3 to 4 months postoperatively and there were no aneurysms at the anastomoses. Enlargement of the graft diameter was minimal. The rate of stenosis at the anastomosis was smaller than that 1-day postoperatively. Even though the thick arterial wall was initially inserted and the intimal hyperplasia was still present at the anastomosis 3 to 4 months postoperatively, the long-term stenosis was relatively mild due to the atrophy in the overlapped walls.

Anastomosis, Surgical↗
PubMed1999

Peroneal nerve palsy caused by intraneural ganglion.

A case of peroneal nerve palsy caused by an intraneural ganglion is presented. The cystic mass was located posterolateral to the lateral femoral condyle and extended along the common peroneal nerve distal to the origin of the peroneus longus muscle. The nerve was compressed in the narrow fibro-osseous tunnel against the fibula neck and the tight origin of the peroneus longus muscle. The nerve was decompressed by complete tumor excision and transection of the origin of the peroneus longus muscle. Full recovery of nerve function was obtained in 6 months.

Cysts↗
PubMed1999

Acute arterial occlusion associated with total knee arthroplasty.

Acute arterial occlusion is a rare but limb-threatening complication in total knee arthroplasty. Most of the previously reported cases of this complication required surgical intervention. This report illustrates an unusual case of this complication that was managed conservatively with an acceptable outcome. The case is also indicative of the etiology and the optimal prevention of this complication. In a patient with advanced arteriosclerosis, as indicated by vascular calcification around the knee or in the abdomen, knee arthroplasty should be performed without a tourniquet, and intra-operative manipulation should be done cautiously because of the potential for intimal disruption.

Acute Disease↗
PubMed1999

Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL).

OPLL (ossification of the posterior longitudinal ligament of the spine) is a common form of human myelopathy with a prevalence of as much as 4% in a variety of ethnic groups. To clarify the genetic factors that predispose to OPLL, we have studied ttw (tiptoe walking), a mouse model that presents ectopic ossification of the spinal ligaments similar to OPLL and have found that the ttw phenotype is caused by the nonsense mutation of the gene encoding nucleotide pyrophosphatase (NPPS), a membrane-bound glycoprotein thought to produce inorganic pyrophosphate, a major inhibitor of calcification and mineralization. To investigate a possible role of NPPS in the etiology of OPLL, we have examined its genetic variations in OPLL patients. A total of 323 OPLL patients was screened by means of polymerase chain reaction/single-strand conformation polymorphism analysis covering all the exons and their surrounding introns, plus about 1.5-kb of the promoter region. We identified ten nucleotide variations in the NPPS gene; five of the alterations caused amino-acid substitutions, and two of them were found specifically in OPLL patients. Subsequently, we performed an association study using these variations and found a significant association of an allele, viz., a deletion of T at a position 11 nucleotides upstream from the splice acceptor site of intron 20 (IVS20-11delT), with OPLL; the proportion of the individuals having this deletion was significantly higher (P = 0.0029) in OPLL patients than in controls, indicating that those who have this variation may be more susceptible to the abnormal ossification of the spinal ligaments. Thus, our study suggests that NPPS plays an important role in the etiology of human OPLL.

Aged↗
PubMed1999

Nontraumatic lumbar vertebral compression fracture as a risk factor for femoral neck fractures in involutional osteoporotic patients.

To screen a potential risk factor for femoral neck fracture, we characterized lumbar vertebral fractures in 120 patients with femoral neck fractures (19 men, 101 women; mean age, 78.7 years) by investigating the frequency of patients with lumbar vertebral fracture, the number of vertebral fractures per patient, and the severity of deformity of the fractured vertebral bodies. These findings were compared with data gathered from a population of age- and sex-matched control patients (20 men, 89 women; mean age, 77.6 years) who had no evidence of femoral neck fracture. The heights of the anterior and posterior walls together with the midpart of the lumbar vertebrae were measured on lateral radiographs to identify fractures. The extent of height loss in the fractured vertebrae was calculated for each group. The incidence of patients with vertebral compression fractures was significantly higher in the femoral neck fracture group than in the control group (65.0% vs 41.1%). In terms of age, the difference in the incidence of vertebral fractures in the two groups was greater in the less aged (60-79 years old) than in the more aged (>80 years old) population. The mean number of lumbar vertebral fractures was also significantly greater in the femoral neck fracture group than in the control group (1.59 +/- 1.39 vs 0.75 +/- 1.19; P < 0.001). The incidence of more deformed vertebral fractures, which were defined as a vertebral height loss of more than 50%, was also significantly higher in the group with femoral neck fracture than in the control group (23.0% vs 7.3%). Based on these results, we concluded that multiple and more severely deformed vertebral fractures might represent a high risk for femoral neck fracture, particularly in patients less than 79 years of age. Care measures that encompass fall prevention and protection of proximal femurs in addition to drug therapy for osteoporosis should be recommended to individuals in this category.

Age Factors↗
PubMed1999

Accurate pedicle screw insertion under the control of a computer-assisted image guiding system: laboratory test and clinical study.

We used a commercially available computer-assisted navigation system (StealthStation; Sofamor Danek, Memphis, TN, USA) in both an in-vitro and a clinical study performed in 1996-1998. The basic data used for navigation were preoperative computed tomography (CT) scan imaging data. The position of the probe or drill guide was superimposed in real-time on a monitor. For the in-vitro study, ten plastic lumbar spine models (50 vertebrae) were used. The entrance hole for the screw was made by drilling, following navigation. Using the navigation system, we drilled 88 holes through the pedicles into the vertebral bodies of 44 vertebral models. All 88 pedicle holes were contained within the pedicle without perforation. The mean deviation of the hole positions from the surgical plan was 1.78 +/- 0.81 mm, and the mean angular deviation was 2.28 degrees +/- 1.92 degrees. In 29 patients, using the navigation system, we introduced 169 pedicle screws at the planned position. Fifty-one screws were used for thoracic and 118 screws for lumbar spinal fixation. All screws correctly passed through the pedicles. There were no neurological complications after surgery. Using this guided surgery system, we achieved satisfactory results both in the laboratory and in a clinical setting.

Adolescent↗
PubMed1999

Genomic organization, mapping, and polymorphisms of the gene encoding human cartilage intermediate layer protein (CILP).

The CILP gene encodes a proform of two polypeptides. One of them, cartilage intermediate layer protein (CILP), is a non-collagenous protein recently isolated from human articular cartilage. The other is homologous to a porcine nucleotide pyrophosphohydrolase (NTPPHase) whose enzymatic activity is highest in articular tissue. The investigation reported here revealed that the CILP gene consists of nine exons spanning approximately 15 kb of genomic DNA on chromosome 15q22. We also report six single nucleotide variations in this gene; five of them cause amino acid changes and the most common of them substitutes isoleucine for threonine at codon 395.

Cartilage, Articular↗
PubMed1999

Percutaneous transpedicular biopsy of thoracic and lumbar vertebrae--method and diagnostic validity.

BACKGROUND: Percutaneous transpedicular needle biopsy was performed on thoracic and lumbar vertebral bodies with a thin trocar (2.0 mm outer diameter) under observation with a conventional X-ray image intensifier in order to establish a correct histopathological diagnosis. We also evaluated the clinical validity of this less invasive diagnostic method in terms of the accuracy of the pathological diagnosis. METHODS: Twenty-eight thoracic or lumbar vertebrae of 26 patients with abnormalities observed on routine X-ray, CT, or MRI images underwent percutaneous transpedicular needle biopsy under local anesthesia. A threaded trocar with an outer diameter of 2.0 mm was screwed into the intra-vertebral lesion through the pedicle from the posterior side under control of X-P imaging, and a small amount of tissue or fluid was collected. RESULTS: For all patients but two, where inadequate specimens were obtained, correct diagnoses were made, which were confirmed by pathological diagnoses of massive tissue obtained during subsequent reconstructive surgery. CONCLUSIONS: The accuracy rate of diagnosis with this biopsy method was 92% without significant intra- or postoperative complications. Therefore, it can be concluded that this less invasive biopsy method used in conjunction with conventional X-ray apparatus has good potential to result in correct preoperative diagnosis of thoracic and lumbar lesions so that more effective treatment can be determined.

Adult↗
PubMed1999

Advantages of concurrent use of anabolic and antiresorptive agents over single use of these agents in increasing trabecular bone volume, connectivity, and biomechanical competence of rat vertebrae.

The purpose of this study was to evaluate the usefulness of a combination regimen of anabolic and antiresorptive agents in increasing skeletal quantity and quality in comparison to a single-drug regimen with these agents. We examined histomorphometrically and biomechanically the effects of separate and combined administration of intermittent parathyroid hormone (PTH) and estrogen or bisphosphonate on both axial and appendicular skeletons of male Wistar rats, which were 4 months old and weighed approximately 300 g at the beginning of the treatment. The animals were untreated or injected with vehicle, recombinant human PTH(1-84) (PTH; 100 microg/kg daily), 17beta-estradiol (E2, 500 microg/kg every other day), incadronate disodium (YM175, 80 microg/kg every other day), combined PTH and E2 (PTH + E2), or a combination of PTH and YM175 (PTH + YM175). After 1 month of treatment, the three groups in which PTH was administered (PTH, PTH + E2, and PTH + YM175) had significantly higher trabecular bone volume and connectivity in the proximal tibial metaphyses (PTMs) compared with the untreated and vehicle-treated groups, whereas only combination groups (PTH + E2 and PTH + YM175) showed significant increases in these indices in the lumbar vertebrae. This site-related discrepancy was attributed to the fact that PTH significantly elevated bone resorption not in the PTMs but in the vertebrae. This increased bone resorption in the vertebrae was suppressed by the addition of an antiresorptive agent. As a result, trabecular bone mass, connectivity, and mechanical strength of the vertebrae were significantly increased from control levels only in the concurrent treatment groups (PTH + E2 and PTH + YM175). The superior skeletal effects of PTH cotherapy over PTH monotherapy were not seen with regard to bone mass, but with increased connectivity and mechanical strength. The concurrent use of PTH and an antiresorptive agent has been shown to be superior to the single use of PTH for enhancing these properties of rat vertebrae, which encourages future research, especially in larger animals.

Animals↗