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We report a case of recurrent knee valgus deformity in a patient with Ellis–van Creveld syndrome. Varus osteotomy, distraction osteogenesis, or epiphyseal stapling is one treatment option for valgus malalignment to improve appearance, gait, and function. However, surgical correction of valgus knee deformity by varus osteotomies of the proximal tibia was not maintained postoperatively, necessitating additional varus osteotomies of the distal femur in this case. The main cause of recurrence was attributed to large bony defect of the anterior segment of the proximal tibia, in addition to depression of the lateral tibial plateau.

During the past 20 years, we have found that acridine orange (AO) selectively accumulates in musculoskeletal sarcomas in vivo or exerts selective cytocidal effects against sarcoma cells in vitro after illumination of the tumor cells with visible light or irradiation of the cells with low-dose X-rays. Based on the data obtained from basic research, we have employed reduction surgery followed by photo- or radiodynamic therapy using AO (AO-PDT & RDT) in 71 patients with musculoskeletal sarcomas, in an attempt to maintain excellent limb function in the patients. We have obtained good local control rates and remarkably better limb functions with this approach as compared to the results obtained with the conventional wide resection surgery. Our basic research demonstrated that AO accumulates densely in intracellular acidic vesicles, especially lysosomes, in an acidity-dependent manner. In cancer cells that proliferate under hypoxic conditions or with Warburgs effect, active glycolysis produces an enormous number of protons, which are released by the cells via proton pumps into the extracellular fluid or lysosomes to maintain a neutral pH of the cytosolic fluid. Cancer cells contain many strongly acidic lysosomes of large sizes; therefore, AO shows marked and prolonged accumulation in the acidic lysosomes of cancer cells. Photon energy excites the AO resulting in the production of activated oxygen species, which oxidize the fatty acids of the lysosomal membrane, resulting in the leakage of lysosomal enzymes and protons, followed by apoptosis of the cancer cells. Based on these observations, we conclude that AO-PDT & RDT target acidic vesicles, especially the lysosomes, in cancer cells, to exhibit selective anti-cancer cell activity. Therefore, it is suggested that AO excited by photon energy has excellent potential as an anticancer “Magic Bullet”.

Purpose. To compare percutaneous transpedicular vertebroplasty using calcium phosphate cement (CPC) versus conservative treatment for osteoporotic vertebral fractures.Methods. Eight men and 28 women aged 61 to 99 (mean, 80) years with osteoporotic vertebral fractures underwent percutaneous transpedicular vertebroplasty using CPC. During the same period, 6 men and 32 women aged 53 to 93 (mean, 77) years underwent conservative treatment. The indication for vertebroplasty was a painful unstable fracture, with mobility of the vertebral body shown on flexion and extension lateral radiographs. Fractures without mobility despite deformity were treated conservatively.Results. In the vertebroplasty group, all patients benefited from reduced back pain immediately after surgery, and pain relief was maintained at the latest follow-up. However, correction loss continued until one month after the operation. The mean visual analogue score for pain decreased significantly from preoperation to one day after surgery (9.3 vs. 6.2, p=0.02), and further decreased to 2.8 (p=0.04) on day 3 or 4 when ambulation began, and to 1.5 at the one-month follow-up and 1.4 at the final follow-up (mean, 14 months). The mean duration of analgesic treatment was significantly shorter in the vertebroplasty than conservatively treated group (10.2 vs. 63.5 days). All patients in the vertebroplasty group achieved bone union, with no adjacent vertebral fractures. However, in patients having conservative treatment, there were 2 adjacent vertebral fractures and 4 pseudarthroses, and the collapse continued for several months.Conclusion. Percutaneous transpedicular vertebroplasty using CPC achieves immediate pain relief and reduces the risk of vertebral body collapse and pseudarthrosis among elderly patients with osteoporotic vertebral compression fractures.

Purpose. To assess the association between vertebral fractures and mortality.Methods. 419 women and 210 men aged 60 to 98 (mean, 73) years participated in an osteoporosis screening exercise. Patient age, gender, comorbidity, lumbar pain, smoking, and alcohol consumption were recorded, as were the number of vertebral fractures and bone mineral density. Vertebral fractures were evaluated using lateral radiographs and quantitative morphometry. Anterior, central, and posterior vertebral heights were measured; vertebral fractures were defined as a decrease of =20% in any of these heights.Results. 131 (21%) of the participants had vertebral fractures. At the 10-year follow-up, 121 (19%) of the participants (55 men and 66 women) had died; 43 of them had vertebral fractures and 78 did not. The respective 10-year survival rates for participants with and without vertebral fractures were 69% and 86% (p<0.0001). The survival rate was lower in those with greater number of vertebral fractures (76% for those with one or 2 fractures and 50% for those with =3 fractures). Multiple regression analysis showed that advanced age (p<0.0001), male gender (p=0.003), and presence of vertebral fractures (p=0.013) correlated significantly with survival.Conclusion. The presence and number of vertebral fractures were associated with mortality. Prevention of vertebral fractures may be important for improving the prognosis of patients with osteoporosis.

Soluble fibrin (SF) and D-dimer are useful for making the diagnosis of deep vein thrombosis (DVT). However, the evidence for using such markers and optimal timing to diagnose postoperative DVT are unclear. We evaluate the usefulness of SF and D-dimer testing for the diagnosis of postoperative DVT. A total of 207 patients who had total hip arthroplasty or knee arthroplasty were evaluated. SF and D-dimer were tested on postoperative days 1 and 7. DVT was confirmed with ultrasonography. SF level on postoperative day 1 was the most useful, although D-dimer evaluation on postoperative days 1 and 7 was also useful. Using a SF cut-off of more than 4.00 μg ml−1, the sensitivity was 90%, the specificity was 33%. Although the SF and D-dimer tests cannot be used as stand-alone tests, SF and D-dimer are valuable screening tools. We recommend two-stage screening including first with the SF or D-dimer test, followed by ultrasonography or venography.

OBJECTIVE: Osteopontin (OPN) is an extracellular matrix glycoprotein that has been recognized as a potential inflammatory cytokine. The function of OPN is modulated by protease digestion, and a thrombin-cleaved form of OPN is involved in the pathogenesis of various inflammatory disorders. We examined thrombin-cleaved OPN products in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial fluid samples were obtained from knees of 20 patients with RA and 111 patients with OA. Thrombin-cleaved OPN product was determined using Western blotting. Levels of thrombin- cleaved and full-length OPN in synovial fluid were determined by ELISA. Synovia were analyzed by immunohistochemistry using an antibody specific to the thrombin-cleaved form. RESULTS: Immunoblotting showed the presence of thrombin-cleaved OPN in synovial fluid from patients with RA and OA. ELISA results showed no difference between concentrations of full-length OPN in the synovial fluid of RA and OA patients; however, thrombin-cleaved OPN concentrations in RA synovial fluid samples were roughly 30-fold higher compared with OA samples (p < 0.001). Synovial fluid concentrations of thrombin-cleaved OPN in RA did not correlate with C-reactive protein levels. Immunohistochemistry of the synovium showed stronger reactivity in RA than in OA samples. CONCLUSION: Local generation of thrombin-cleaved OPN was increased in RA joints. Thrombin-cleaved OPN may be a useful biochemical marker of RA.

Background: Soluble fibrin (SF) is considered to be useful for the diagnosis of thrombosis, however, evidence for the diagnosis of pre-thrombosis by SF is still not well established. Objective: The present study was designed to evaluate the usefulness of new SF assay (New SF) in the diagnosis of thrombosis and a pre-thrombotic state. Patients/Methods: The plasma concentrations of New SF were measured in 748 inpatients suspected to have thrombosis and they correlated with thrombosis. Results and Conclusions: The plasma concentrations of New SF were significantly higher in patients with disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT) and cerebral thrombosis, in comparison to those of patients without thrombosis, but there was no significant difference of the New SF assay between patients with thrombosis and those after an operation. The New SF assay was moderately correlated with the other two SF assays. The New SF levels were significantly higher in patients before the onset of thrombosis than in those without thrombosis but other hemostatic molecular markers were not significantly elevated. Our findings suggest that the New SF assay is useful for the diagnosis of not only thrombosis but also of a pre-thrombotic state.

Fibrin-related markers, such as fibrin and fibrinogen degradation products (FDP) and D-dimer, are considered useful for the diagnosis of thrombosis. However, the evidence for making a diagnosis of thrombosis based on fibrinrelated markers is still not yet well established. The plasma concentrations of soluble fibrin and D-dimer were prospectively measured in 680 inpatients suspected of having thrombosis between October 1, 2003 and January 31, 2005, and correlated with thrombosis. The normal ranges of D-dimer and FDP were within 0.76 μg/ml and 1.50 μg/ml, respectively. Out of 680 patients, 129 patients showed plasma concentrations associated with thrombosis, including 73 with deep venous thrombosis (DVT)/ pulmonary embolism (PE). The plasma D-dimer and FDP concentrations were significantly higher in the patients with thrombosis than in the patients without thrombosis, but there were no significant differences in the D-dimer and FDP levels among the patients with thrombosis. The plasma D-dimer levels were significantly correlated with the plasma FDP levels in all the patients and there was no significant difference in the ratio of FDP/ D-dimer among the various diseases. A ROC analysis showed that both FDP and D-dimer were useful for the diagnosis of all types of thrombosis and DVT. The cutoff values of D-dimer (3.8 μg/ml) and FDP (7.7 μg/ml) had high sensitivity, specificity and negative predictive values (NPV) but low positive predictive value. Our findings suggest that FDP showed a close correlation with D-dimer, which is known to be a marker for a hypercoagulable state, and it is also reflects a high risk for thrombosis.

Expression of tenascin-C reappears in articular cartilage of persons with osteoarthritis (OA), while it is almost abolished in normal mature cartilage. Tumor necrosis factor- (TNF-), a proinflammatory cytokine, is upregulated in OA cartilage and is involved in the progression of OA, and stimulates tenascin-C expression in other types of cells. We investigated regulation of tenascin-C expression by TNF- through nuclear factor-B (NF-κB) in OA cartilage in vivo and in vitro. METHODS: Human articular cartilages were obtained from patients with OA and immunofluorescence examination of tenascin-C and the activated RelA subunit was performed. Cultured chondrocytes isolated from human OA cartilage were treated with TNF- and with SN50. Activation of RelA subunit of NF-κB was examined by immunolabeling. Changes in tenascin-C protein concentrations were determined by immunofluorescence of cells after monensin treatment and Western blot analysis of the cell lysates, and mRNA levels were analyzed by quantitative real-time polymerase chain reaction. RESULTS: Increased intensity of tenascin-C staining was observed in the damaged cartilage compared with normal cartilage. Activated RelA staining in chondrocyte nuclei was prominent in tenascin-C-positive areas of OA cartilage. Treatment of cultured chondrocytes by TNF- induced translocation of activated RelA to the nuclei, followed by upregulation of tenascin-C expression in both mRNA and protein. Treatment with SN50 inhibited increases of RelA and tenascin-C expression in chondrocytes. CONCLUSION: TNF- stimulated tenascin-C expression through NF-κB signaling with RelA activation in cultured OA chondrocytes, suggesting involvement of tenascin-C in OA cartilage remodeling.

Abstract: Hypoxia-inducible factor (HIF)-1α is a transcription factor that supports the adaptation of human cancer cells to hypoxia and tumor growth and progression. The overexpression of HIF-1α protein has been reported to be associated with a worse prognosis in various cancers. However, the expression of HIF-1α in soft-tissue sarcomas has not yet been characterized. The expression of HIF-1α protein was immunohistochemically determined in 49 specimens of soft-tissue sarcomas including malignant fibrous histiocytoma (29 patients), synovial sarcoma (12 patients), leiomyosarcoma (four patients), and malignant peripheral nerve sheath tumors (four patients). The 49 samples consisted of 40 primary lesions and nine local recurrences. An immunohistochemical analysis showed the nuclear accumulation of HIF-1α protein in 35 (71.4%) samples. The expression of HIF-1α was negative in 14 (28.6%) cases, weak in nine (18.4%), moderate in 17 (35.4%), and strong in nine (18.4%). The patients with a strong or moderate expression of HIF-1α had a significantly shorter overall survival rate in comparison with those with a weak or negative expression in a univariate analysis (P = 0.029; log-rank test) and multivariate analysis (P = 0.018). This is the first report that demonstrated an overexpression of HIF-1α protein to be an independent prognostic factor for soft-tissue sarcomas.

Background and PurposeAlthough many studies have described clinical examination measures for the diagnosis of lumbar spinal instability, few of them have investigated the sensitivity and specificity of the measures that were used. The authors devised a passive lumbar extension (PLE) test for assessing lumbar spinal instability. The purpose of this study was to investigate the sensitivity, specificity, and positive likelihood ratio of this test. Subjects and Methods.The PLE test as well as the instability catch sign, painful catch sign, and apprehension sign tests were done for 122 subjects with lumbar degenerative diseases. The subjects were divided into 2 groups—instability positive and instability negative—on the basis of findings on flexion-extension films of the lumbar spine. The sensitivity, specificity, predictive values, and positive likelihood ratio of each test were investigated. Results.The sensitivity and specificity of the PLE test were 84.2% and 90.4%, respectively. These values were higher than those of other signs. The positive likelihood ratio of the PLE test was 8.84 (95% confidence interval=4.51–17.33). Discussion and Conclusion.The PLE test is an effective method for examining patients for lumbar spinal instability and can be performed easily in an outpatient clinic.

In the past, patients admitted for hip fractures had often sustained a contralateral hip fracture. The incidence of bilateral hip fractures has been reported to be 5%–10%, and in the future the number of bilateral hip fractures is expected to increase with the increase of unilateral hip fractures. We believe that bilateral hip fractures can be efficiently prevented if a fracture on the other side could be predicted after unilateral hip fracture. Therefore, this retrospective study of 835 patients with hip fractures investigated the incidence, prognosis, and risk factors of bilateral hip fractures.

Abstract: Background: In the past, patients admitted for hip fractures had often sustained a contralateral hip fracture. The incidence of bilateral hip fractures has been reported to be 5–10%, and in the future the number of bilateral hip fractures is expected to increase with the increase of unilateral hip fractures. We believe that bilateral hip fractures can be efficiently prevented if a fracture on the other side could be predicted after unilateral hip fracture. Therefore, this retrospective study of 835 patients with hip fractures investigated the incidence, prognosis, and risk factors of bilateral hip fractures. Methods: We examined 835 hip fractures retrospectively in Japan. Among them, we found 94 patients with bilateral noncontemporary hip fractures. We investigated age, sex, interval between the two fractures, type of fractures, cause, physical functioning, and complications. Differences between the unilateral fracture and bilateral fractures groups were analyzed statistically for age, sex, and complications using Student’s t test and the chi-square test. Results: In this study, the mean interval between two fractures was 4.28 years, and the second hip fracture occurred within 5 years in more than 70% of patients. The type of hip fracture was the same in 72.2% of bilateral hip fractures. No difference in age and sex was found between the unilateral and the bilateral groups. However, concerning complications, 22.1% of patients in the unilateral group and 34.8% in the bilateral group had dementia, the difference being significant. Conclusions: These results revealed that the second hip fracture occurred within 5 years of the first in more than 70% of bilateral hip fracture patients and that dementia is a risk factor of bilateral hip fractures.

In ceramic-on-ceramic total hip arthroplasty (THA), modular acetabular component with a sandwich insertion was developed and evaluated mid-term clinical results. 35 hips had undergone cementless ceramic-on-ceramic THA with sandwich cup (Kyocera, Kyoto, Japan). The mean duration of follow-up was 5 years. 6 hips had undergone component revisions. The reasons for revision included infection in 1 hip, dislocation with loosening in 2 hips, alumina liner fractures in 2 hips, and cup dissociation in 1 hip. All femoral and acetabular components showed no loosening in the unrevised hips at the time of the last follow-up. None of the 29 unrevised hips had osteolysis.

A novel hydroxyapatite (HA-A) was developed and we evaluated the slow release of antibiotic in vitro as well as osteoconduction of the material in vivo. HA-A (4 x 4 mm) was synthesized by mixing HA powder, gelatin, and vegetable oil. The material had a bi-modal pore size distribution, with intragranular (10 nm to 10 µm) and intergranular (100 µm) pores, and porosity of 40 vol%, while a control HA had pore sizes ranging from 50 to 300 µm and identical porosity. In vitro drug release was tested using antibiotics soaked on the HA cylinders using a vacuum system. The mean adsorption efficiency was higher for HA-A than for control and higher levels of antibiotic were released from HA-A. Bone ingrowth into the pores was observed for both materials. Since the novel HA showed both the slower release of antibiotic (nanosize pores) and supported excellent osteoconduction (microsize pores), it could be useful for the treatment of osteomyelitis.

Considerable controversy exists concerning the mechanism of axonal regeneration in end-to-side neurorrhaphy. The authors studied the mode of axonal regeneration in end-to-side neurorrhaphy without a perineurial window using a rat sciatic nerve model.

Alginates have a wide variety of potential clinical applications, including use in cell encapsulation, drug delivery, and tissue engineering. Although the compounds are typically used in the form of a calcium hydrogel, alginates in this form possess several disadvantages, including low biodegradability, induction of foreign body reactions, and cytotoxicity secondary to Ca2efflux and contamination with bioincompatible substances. Thus, the goal of the present study was to develop a new method of obtaining sterilized, pure, highly viscous alginate sol from seaweed alginates and to determine its utility as an injectable antiadhesion drug.

Clinical treatment of recurrent symptoms following peripheral nerve decompression is problematic. Removal of scar tissue can produce an inappropriately pronounced healing response and thereby lead to more serious tethering or compression of the nerve. The goal of the present study was to test the ability of viscous injectable pure alginate sol to prevent perineurial adhesion using a rat neurolysis model.

The authors report phosphoglyceride crystal deposition disease in the spine after a lumbar anesthetic given at the time of appendectomy. A 76-year-old Japanese woman with increasing lumbar pain was transported to our hospital in an ambulance. She had tumor-like lesions that had repeatedly appeared in injured soft tissues for >20 years. Osteolytic changes were detected by x-ray in the 12th thoracic vertebra and the 4th lumbar vertebra. Compression of the left L4 nerve root was detected by myelography, and a tumor corresponding to the left L3–L4 intervertebral foramen was determined by computed tomography. An operation to achieve posterior decompression and fusion was performed. The histopathologic tests on this coarse matter revealed a radial deposition of needle crystals and a strong foreign matter reaction in the periphery. Based on the above analyses, the deposited crystals were regarded as phosphoglyceride. Phosphoglyceride crystal deposition disease is characterized by the deposition of crystals of the phospholipid called phosphoglyceride in sites especially susceptible to invasion, such as surgical sites. To our best knowledge, only three cases of phosphoglyceride crystal deposition disease, including this one, have been reported.

The patient was a 48-year-old man in whom a slow progression in walking difficulty occurred over a year. Magnetic resonance imaging (MRI) and computed tomography myelography (CTM) revealed duplicated dura mater from T1 to T12 and spinal cord herniation in the inner layer of the dura at the T4–T5 level. Idiopathic spinal cord herniation with duplicated dura mater was diagnosed, and surgery was performed. Intraoperative findings were of an elliptical defect of about 1 cm in the inner layer of the dura at the T4–T5 level, into which the spinal cord was herniated. A 1.5-cm cephalocaudal incision was created in the inner layer of the dura, and the incarcerated spinal cord was released, resulting in resolution of gait disturbance and an excellent postoperative clinical course. We reviewed the reports of 11 cases of idiopathic spinal cord herniation with duplicated dura mater and summarized the clinical and imaging characteristics as follows: 1) A hernial orifice was found at the T4–T6 level, 2) cross-sectional MRI or CTM showed a “snowman-like” deformation of the spinal cord, and 3) symptoms were often improved by widening the hernia orifice.

OBJECTIVE: Osteoarthritis (OA) is a major cause of disability and represents the most common disease in the aging population. Although the course of the disease is generally assessed using standard radiographic images, biochemical markers may be employed to detect the disease and determine the degree of severity. We developed an enzyme linked immunosorbent assay (ELISA) system using a monoclonal antibody specific for the large-splice variants of tenascin-C (TN-C) and examined whether TN-C in synovial fluid (SF) is an adequate biochemical marker of OA progression. METHODS: SF samples were obtained from knees of 74 patients with OA and 16 without OA. Based on the radiographic grading of the OA severity, the knees were divided into 3 groups: mild, moderate, and severe OA. Expression of TN-C splice variants was examined using immunoblotting. TN-C concentrations were determined by ELISA. RESULTS: Western blotting showed the presence of large TN-C variants in SF from severe OA. TN-C levels were 5-fold higher in OA samples compared to subjects without OA (p < 0.0001). TN-C levels were not different between control cases and mild OA, but increased significantly in moderate (p = 0.0244) and severe OA (p < 0.0001). After adjusting TN-C levels for age, body mass index, and sex, TN-C levels correlated with radiographic progression of knee OA (R2 = 0.404, p < 0.0001). CONCLUSION: TN-C, including the large-variant subunits, is a useful biochemical marker for OA progression in the later stages of disease.

Bone is the third leading site of metastatic disease, after the lung and liver. Pain, pathological fractures, neurological deficits, and forced immobilization significantly decrease the quality of life of patients with bone metastasis. The development of metastasis, from the migration of malignant cells from the primary tumor to their proliferation at a distant site, involves a series of sequential steps: angiogenesis, matrix degradation, cell motility, cell attachment, and cellular proliferation. A better understanding of the pathogenesis of metastasis may be expected to lead to the development of new treatment modalities for bone metastasis. Currently, antiangiogenic agents, matrix metalloproteinase (MMP) inhibitors, and hyperthermia are some of the newer therapeutic modalities that seem to hold promise for the treatment of metastatic bone disease.

Bone is the third leading site of metastatic disease, after the lung and liver. Pain, pathological fractures, neurological deficits, and forced immobilization significantly decrease the quality of life of patients with bone metastasis. The development of metastasis, from the migration of malignant cells from the primary tumor to their proliferation at a distant site, involves a series of sequential steps: angiogenesis, matrix degradation, cell motility, cell attachment, and cellular pro-liferation. A better understanding of the pathogenesis of metastasis may be expected to lead to the development of new treatment modalities for bone metastasis. Currently, antiangiogenic agents, matrix metalloproteinase (MMP) inhibitors, and hyperthermia are some of the newer therapeutic modalities that seem to hold promise for the treatment of metastatic bone disease.

In the present study, we investigated chondrocytic characterization for newly established human chondrosarcoma cell lines. A chondrosarcoma cell line, HCS-TG, was established by the implantation of grade-2 human chondrosarcoma into athymic mice. Cloning of HCS-TG cells from passage 17 was performed. After cell cloning, two clonal-cell lines (HCS-TG C3 and E2) with good proliferative activities were obtained. These cell lines in monolayer culture retained a polygonal morphology. Their doubling times were 68 h and 45 h, respectively. mRNA expressions of type-I, -II, -X, and -XI collagens and aggrecan core protein were detected on reverse-transcription polymerase chain reaction. Protein expression of type-II collagen was confirmed in each cell line using Western blotting. However, there was no expression of type-I collagen. Moreover, gelatin zymography revealed that both cell lines produced extracellular matrices with matrix metalloproteinases 2 and 9. The parental HCS-TG cells had tumorigenicity in athymic mice; however, C3 and E2 were not tumorigenic. New clonal-cell lines HCS-TG C3 and E2 derived from human chondrosarcoma are morphologically chondrocytic in serial monolayer cultures and express chondrocytic phenotypes.

We administered the Maudsley Personality Inventory (MPI) preoperatively to 303 patients with spinal diseases about to undergo surgery. Patients younger than 20 years, patients previously treated in the Department of Psychiatry, and patients with poor postoperative results were excluded. Patients with N-scores (neuroticism scale) of 39 points or greater or L-scores (lie scale) of 26 points or greater were regarded as "abnormal." Based on clinical definitions we identified 24 "problem patients" during the course and categorized them as "Unsatisfied," "Indecisive," "Doctor shoppers," or "Distrustful." Preoperative MPI categorized 26 patients as abnormal; 22 patients categorized as abnormal became problem patients ( p<0.001). MPI sensitivity and specificity was 84.6% and 99.3%, respectively. Preoperative MPI to patients with spinal disease was found to be useful in detecting problem patients.

We present a large dermatofibrosarcoma protuberans on a 52 years‐old woman's back that was successfully treated with transcatheter arterial embolization and radiofrequency ablation. The tumor developed on her back at the age of 14. Surgical treatment was not complete, and it relapsed at age 17 and again at age 24. The tumor enlarged to over 20 × 20 × 10 cm and flooded intermittently. The tumor cells with atypical nuclei were CD34 positive and proliferated in a storiform pattern. These findings were compatible with dermatofibrosarcoma protuberans. She was treated with blood transfusion for severe anemia. Two large feeding arteries were embolized, and the bottom of the tumor was treated with radiofrequency ablation. The tumor reduced in volume by more than 50%. It was then surgically removed and reconstructed with a free mesh skin graft. The combination pretreatment enabled radical resections of a large DFSP without severe complications.

There have been no reports on the effects of the mixture ratio of local bone graft to artificial bone on the outcome of intervertebral bone fusion. The purpose of this study was to determine whether the mixture ratio of local bone removed from laminae and spinous processes to apatite- and wollastonite-containing glass ceramic (AWGC) granules affected fusion rates in spinal fusion. Posterolateral lumbar fusion at two levels without spinal instrumentation was performed in 35 patients who were diagnosed with lumbar spinal canal stenosis. The patients were randomly divided into three groups, each of which received a different mixture ratio of local bone to AWGC granules 21, 11, and 12. The total mass of grafted bone was 20 g in all three groups. The fusion rate was approximately 80 in all three groups. Our results indicate that lumbar posterolateral fusion can be successfully achieved even when the mixture ratio of local bone graft to AWGC granules is 12.

Telomerase is a ribonucleoprotein enzyme that extends telomere specific repeats on the ends of chromosomes. Telomerase activity has been detected frequently in various types of human tumors and has been associated with cell immortality and oncogenesis. Human telomerase reverse transcriptase (hTERT), a telomerase catalytic subunit, reportedly regulates telomerase activity. Little is known about telomerase activity and hTERT mRNA expression in soft tissue tumors. The objective of this study was to clarify the correlation between these two parameters and clinical aggressiveness in soft tissue tumors. In 41 surgically resected soft tissue tumors, telomerase activity was measured by the fluorescence-based telomeric repeat-amplification protocol and hTERT mRNA expression was determined by real-time polymerase chain reaction. Telomerase activity was detected in 52% of sarcomas and in none of the benign soft tissue tumors (P &lt; 0.05). Telomerase activity was found in 77% of 13 locally recurrent sarcomas and in 89% of 9 sarcomas with distant metastasis. The frequency of the presence of telomerase activity in those tumors was significantly greater compared with the frequency of telomerase activity in the other sarcomas (P &lt; 0.05 and P &lt; 0.01, respectively). All telomerase positive sarcomas expressed hTERT mRNA. The mean level of hTERT mRNA expression in sarcomas was significantly greater compared with the mean hTERT mRNA expression level in benign tumors (P &lt; 0.05) and in locally recurrent sarcomas compared with primary sarcomas (P &lt; 0.001). The results of the current study suggest that the detection of telomerase activity and the level of hTERT mRNA expression are useful markers for evaluating the clinical aggressiveness in soft tissue tumors. Cancer 2002;95:1127–33. © 2002 American Cancer Society. DOI 10.1002/cncr.10793

The present study investigates whether changes in barometric pressure influence low back pain in patients with vacuum phenomenon within lumbar intervertebral discs. Twenty-four patients with low back pain were examined 12 with vacuum phenomenon within the intervertebral discs (VP group) and 12 without the vacuum phenomenon (VP − group). All patients consented to an evaluation of low back pain in a hyperbaric oxygen chamber. In the VP () group, low back pain became more severe in one patient when atmospheric pressure was elevated, and in eight patients when atmospheric pressure was decreased. In the VP (−) group, two patients experienced more severe low back pain when atmospheric pressure was decreased. Our study demonstrated that low back pain might be aggravated by atmosphere depression in patients with lumbar disease associated with the vacuum phenomenon.

Our study focuses on the antineoplasmic action of hyperthermia. In this study, use of a heat-generating cement was exploited for the management of pathological and impending fractures in malignancies. The cement contains magnetic powder in ceramic particles and generates wellregulated heat when a magnetic field is applied externally. Eighteen rabbits were inoculated with blocks of VX2tumor into one of their tibia. One week after the procedure, 9 rabbits were exposed to a magnetic field (HT group) while the remaining 9 rabbits were not (non-HT group). In rabbits killed between 20 and 42 days after the VX2inoculation, the circumference of the operated leg was 7.9 ± 0.3cm and 10.2 ± 1.0cm (mean ± SE) in HT and non-HT groups, respectively (P< 0.05). Histological findings revealed the regressive change in tumor tissue of the HT group. By radiographs, pathological fractures and cortical bone destruction were seen in 5 and 8 rabbits in the non-HT group, respectively, but in the HT group these effects were absent in all the rabbits except 1 in which a definite diagnosis has not been made. Our findings demonstrate that controlled hyperthermia therapy using a newly developed bone cement suppresses tumor growth and prevents local bone destruction caused by VX2tumors.

Abstract.:  Our study focuses on the antineoplasmic action of hyperthermia. In this study, use of a heat-generating cement was exploited for the management of pathological and impending fractures in malignancies. The cement contains magnetic powder in ceramic particles and generates well-regulated heat when a magnetic field is applied externally. Eighteen rabbits were inoculated with blocks of VX2 tumor into one of their tibia. One week after the procedure, 9 rabbits were exposed to a magnetic field (HT group) while the remaining 9 rabbits were not (non-HT group). In rabbits killed between 20 and 42 days after the VX2 inoculation, the circumference of the operated leg was 7.9 ± 0.3 cm and 10.2 ± 1.0 cm (mean ± SE) in HT and non-HT groups, respectively (P < 0.05). Histological findings revealed the regressive change in tumor tissue of the HT group. By radiographs, pathological fractures and cortical bone destruction were seen in 5 and 8 rabbits in the non-HT group, respectively, but in the HT group these effects were absent in all the rabbits except 1 in which a definite diagnosis has not been made. Our findings demonstrate that controlled hyperthermia therapy using a newly developed bone cement suppresses tumor growth and prevents local bone destruction caused by VX2 tumors.

Using a fluorescent differential display (FDD) technique, a novel cDNA was identified by screening for gene expressed differentially between the Dunn osteosarcoma cell line and the LM8 cell line, an isolated variant of the Dunn cell line that has high metastatic potential to the lung. Molecular cloning of the cDNA revealed the clone has similarity to a bacterial fermentation enzyme, the citrate lyase β-subunit (CL-β). Northern blot and competitive reverse transcription-PCR (RT-PCR) analysis revealed up-regulation of the gene in the LM8 cell line. An RNA Master blot indicated that the mRNA encoding CL-β is expressed abundantly in murine heart, liver, and kidney. A human expressed sequence tag (EST) database search suggested that a similar cDNA is expressed in humans. A gene with identical sequence is located on chromosome 13 in the genome database (Sanger centre, UK). These data suggest that a citrate fermentation pathway may exist in eukaryotes including mammals.

Monocytes–macrophages are converted to multinucleated giant cells by stimulation with various cytokines, and osteoclasts are the multinucleated giant cells derived from a monocyte–macrophage lineage. However, at present, the fusion peptides have not been clearly identified in monocytes–macrophages. The ADAM are a family of transmembrane glycoproteins that have a role in various biological functions. Interestingly, fertilin-α, ADAM9, and ADAM11 have potential fusion peptides. In this study, which ADAM was specifically expressed in monocytes stimulated with anti-CD98 antibody or RANKL and which factor(s) was functioning in monocytes as a fusion protein were investigated. ADAM1, 8, 10, 12, 15, 17, 20, and 21 mRNAs are expressed in blood monocytes incubated with control antibody, anti-FRP-1/CD98 antibody, or RANKL + M-CSF, while ADAM2, 7, 11, 13, 19, 23, 29, and 30 mRNAs could not be detected in these blood monocytes. Expression of ADAM9 and ADAM10 mRNAs are enhanced by either RANKL + M-CSF or anti-CD98 antibody. The expression of ADAM9 and ADAM10 is also induced in blood monocytes by anti-CD98 mAb. An anti-ADAM9 antibody enhances CD98-mediated cell aggregation, while it blocks CD98-mediated and RANKL-mediated multinucleated giant cell formation. A hydroxamate-based metalloprotease inhibitor, SI-27, which is found to suppress ADAM9 activity, suppresses multinucleated giant cell formation. New protein synthesis is necessary for the expression of ADAM9 mRNA and genistein suppresses induction of ADAM9 mRNA. This is the first report that ADAM9 is involved in monocyte fusion, such as CD98-mediated and RANKL-mediated cell fusion of blood monocytes. Furthermore, AMAM9 is one candidate for a fusion peptide in blood monocytes.

We report a patient with severe varus deformity and tibial shortening caused by dysplasia epiphysealis hemimelica (DEH), a rare skeletal developmental disorder characterized by an osteocartilaginous tumor arising from an epiphysis in young children. Limb lengtheninig and angular correction was performed successfully, with an excellent result without abnormal bone growth.

Abstract.: We report a patient with severe varus deformity and tibial shortening caused by dysplasia epiphysealis hemimelica (DEH), a rare skeletal developmental disorder characterized by an osteocartilaginous tumor arising from an epiphysis in young children. Limb lengtheninig and angular correction was performed successfully, with an excellent result without abnormal bone growth.

The two pathways to osteoclastogenesis, RANKL-mediated and CD98-mediated osteoclastogenesis, have recently been reported. RANKL, OCIF, and TIMP-3 mRNAs are not found in monocytes freshly isolated or incubated with anti-FRP-1/CD98hc antibody. RANK, TACE, and M-CSF mRNAs can be detected in these cells. Interestingly, the expressed amount of RANK mRNA increases by cultivation of monocytes with anti-CD98hc antibody and maximal expression is observed in osteoclast-like cells. CD98-mediated cell aggregation and multinucleated giant cell formation are blocked by OCIF. OCIF also suppressed the CD98-mediated induction of Sp1 and c-src mRNAs in monocytes. Soluble RANK shows no effect on CD98-mediated cell aggregation and multinucleated giant cell formation. When blood monocytes were incubated with RANKL and M-CSF, c-src and Sp1 mRNAs were first found in blood monocytes incubated with these cytokines for 7 days. On the contrary, c-src mRNA could be detected 3 h after treatment of blood monocytes with anti-CD98hc mAb. LAT-1 mRNA was not found, and the expression levels of Y+LAT-1 and Y+LAT-2 mRNAs were not changed in monocytes stimulated without or with anti-CD98hc mAb or RANKL and M-CSF. An inhibitory mAb directed against CD98hc, HBJ 127, shows a suppressive effect on RANKL-mediated cell aggregation and cell fusion. Thus, there is cross-talk between these two pathways.

Freshly isolated human blood monocytes expressed neither c-src mRNA nor c-Src. However, when monocytes were incubated with anti-CD98 heavy chain (HC) mAb, expression of c-src mRNA, c-Src, and activated c-Src was induced. Many binding sites for the ubiquitous transcription factor Sp1 were identified in the promoter region of the c-src gene. Surprisingly, Sp1 and Sp1 mRNA were not found in monocytes that were freshly isolated or incubated with control antibody. Stimulation with anti-CD98HC mAb also resulted in the expression of Sp1 and its translocation to the nucleus. Herbimycin A, genistein, manumycin A, PD-98059, SB203580, and HBJ127 suppressed CD98HC-mediated c-src and Sp1 mRNA induction. On the contrary, H-7, Wortmannin, HA1077, and Y-27632 showed no effect on c-Src and Sp1 induction. Furthermore, anti-CD98HC mAb induced activation of tyrosine kinases and ERK kinases. These findings suggest that the tyrosine kinase(s)-Ras-MAPK-Sp1 pathway(s) is involved in CD98HC-mediated induction of c-Src in human blood monocytes.

Abstract Significant progress has occurred in the molecular analyses of bone and soft-tissue tumors, and genetic studies have led to the development of important new diagnostic tools for the clinical management of patients with sarcomas. The detection of fusion genes induced by tumor-specific translocations, such as EWS-FLI1 in Ewing's sarcoma, SYT-SSX in synovial sarcoma, and CHOP-FUS in myxoid liposarcoma, is becoming significant for clinical diagnosis, because these sarcomas are often indistinguishable from other bone and soft-tissue tumors. Gene therapies with several gene transfer systems have been employed for some incurable cancers. It has been demonstrated that a Herpes simplex virus thymidine kinase (HSV-tk) gene can convert certain nucleoside analogs, such as ganciclovir, which disrupt DNA synthesis and are toxic to nucleosides. Human chondrosarcoma cells transduced with the HSV-tk gene were more sensitive to the cytotoxity of ganciclovir than non-transduced cells. Coculture of chondrosarcoma cells with and without the HSV-tk gene showed a bystander effect. The local injection of gene transduced cells into the chondrosarcoma implanted in nude mice markedly reduced tumor size after the administration of ganciclovir. These results suggested the possibility of gene therapy for chondrosarcoma.

Significant progress has occurred in the molecular analyses of bone and soft-tissue tumors, and genetic studies have led to the development of important new diagnostic tools for the clinical management of patients with sarcomas. The detection of fusion genes induced by tumor-specific translocations, such as EWS-FLI1 in Ewing’s sarcoma, SYT-SSX in synovial sarcoma, and CHOP-FUS in myxoid liposarcoma, is becoming significant for clinical diagnosis, because these sarcomas are often indistinguishable from other bone and soft-tissue tumors. Gene therapies with several gene transfer systems have been employed for some incurable cancers. It has been demonstrated that a Herpes simplexvirus thymidine kinase (HSV-tk) gene can convert certain nucleoside analogs, such as ganciclovir, which disrupt DNA synthesis and are toxic to nucleosides. Human chondrosarcoma cells transduced with the HSV-tkgene were more sensitive to the cytotoxity of ganciclovir than non-transduced cells. Coculture of chondrosarcoma cells with and without the HSV-tkgene showed a bystander effect. The local injection of gene transduced cells into the chondrosarcoma implanted in nude mice markedly reduced tumor size after the administration of ganciclovir. These results suggested the possibility of gene therapy for chondrosarcoma.

Spindle‐shaped cells were established from four giant‐cell tumors of bone. When human blood monocytes were co‐cultured with these cells, multinucleated giant‐cell formation of monocytes was induced. Intriguingly, even when a filter (pore size: 0.45 μm) was interposed between monocytes and the spindleshaped cells, polykaryocytes also appeared. These multinucleated giant cells were positive for tartrateresistant acid phosphatase, expressed calcitonin receptor, and showed bone‐resorption activity, characteristics of osteoclast‐like cells. These findings indicate that soluble factors secreted from these cells play an important role in osteoclast‐like cell formation from blood monocytes. These data additionally suggest that these cells support osteoclast‐like cell formation in giant‐cell tumors of bone. The cells also expressed mannose receptor, fibronectin, receptor activator of nuclear factorkB, and several cytokine mRNAs, including interleukin‐6, receptor activator of nuclear factorkB ligand/osteoclast differentiation factor/osteoprotegerin ligand, and macrophage colony‐stimulating factor, However, all of these molecules except receptor activator of nuclear factorkB ligand mRNA could also be detected in control HeLa and CV‐1 cells. Although the soluble receptor activator of nuclear factorkB ligand has not been found under physiological conditions, it is possible that it is cleaved by cellular proteases and the truncated receptor activator of nuclear factorkB is released from cells. Identification of the soluble factors capable of inducing osteoclast formation from blood monocytes is a pressing problem to be solved.