Core Needle Percutaneous Transpedicular Vertebral Body Biopsy: A Study of 128 Cases.

STUDY DESIGN: We report an accurate technique for percutaneous transpedicular core needle biopsy of vertebral body lesions, and evaluate its effectiveness for histologic diagnosis retrospectively. OBJECTIVE: The purpose of this study is to evaluate the effectiveness and accuracy of this method retrospectively. SUMMARY OF BACKGROUND DATA: Better knowledge of vertebral pedicle morphometry has led to the development of transpedicular fixation techniques in spinal surgery. After experience with these techniques, we have been performing percutaneous transpedicular vertebral body core needle biopsies (transpedicular biopsy) for histologic diagnosis since 1993. METHODS: A total of 128 patients who had undergone transpedicular biopsy for T1-L5 vertebral body lesions were evaluated. The biopsies were carried out under local anesthesia, except in children, for whom general anesthesia was used. Biopsy specimens were obtained by passing 8 or 11 G needle biopsy instruments percutaneously through the pedicle into the site of the lesion under C-arm fluoroscopy guidance. Histologic analyses were performed, and the accuracy and effectiveness of this technique were evaluated. RESULTS: The pathologic evaluations were definitive in 120 patients (93.8%) and not diagnostic in 8. The accuracy of the results differed among the diagnostic categories. Diagnostic accuracy was 78.6% for primary neoplasms and 97.0% for metastatic neoplasms. There was a significant difference in the diagnostic criteria and spinal segment. True positive rate was higher in the thoracic spine (92.2%) than that of lumbar spine (76.6%). CONCLUSIONS: Transpedicular biopsy is a useful procedure for evaluation of thoracic and lumbar vertebral body lesions.

Morphology of the femoral insertion site of the medial patellofemoral ligament.

PURPOSE: The purpose of this study was to identify the femoral insertion of the medial patellofemoral ligament (MPFL) and related osseous landmarks. METHODS: A total of 31 unpaired human cadaveric knees were studied. The MPFL was identified, and the site of its femoral insertion was marked. Three-dimensional images were created, and the location and morphology of the femoral insertion of the MPFL and related osseous structures were analyzed. RESULTS: The MPFL was identified in all knees. The femoral insertion of the MPFL was elliptical in shape, and the mean surface area was 56.5 ± 16.9 mm(2). The characteristic features of the femoral insertion of the MPFL could not be identified, but the adductor tubercle was clearly identified in all knees. The centre of the femoral insertion of the MPFL was 10.6 ± 2.5 mm distal to the apex of the adductor tubercle on the long axis of the femur, and the position of the insertion site was consistent in all knees. CONCLUSION: The adductor tubercle was clearly identified as an osseous landmark. The femoral insertion of the MPFL was approximately 10 mm distal to the adductor tubercle. These findings may improve understanding of the anatomy of the femoral insertion of the MPFL and may assist surgeons in performing anatomical reconstruction.

Fragment-Based Discovery of Allosteric Inhibitors of SH2 Domain-Containing Protein Tyrosine Phosphatase-2 (SHP2).

The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signaling and inhibit the proliferation of RTK-driven cancer cell lines. Here, we describe the first reported fragment-to-lead campaign against SHP2, where X-ray crystallography and biophysical techniques were used to identify fragments binding to multiple sites on SHP2. Structure-guided optimization, including several computational methods, led to the discovery of two structurally distinct series of SHP2 inhibitors binding to the previously reported allosteric tunnel binding site (Tunnel Site). One of these series was advanced to a low-nanomolar lead that inhibited tumor growth when dosed orally to mice bearing HCC827 xenografts. Furthermore, a third series of SHP2 inhibitors was discovered binding to a previously unreported site, lying at the interface of the C-terminal SH2 and catalytic domains.

Limb function after excision of a deltoid muscle sarcoma.

BACKGROUND: Limb function after excision of deltoid muscle sarcomas has not been thoroughly investigated, although a large defect of soft tissue often causes some degree of dysfunction after wide excision. We formulated a hypothesis that the limb functional results depend on the volume of the excised deltoid muscle and examined the clinical outcomes in patients with a sarcoma in the deltoid muscle treated by surgical resection. METHODS: The clinical outcomes of 8 patients with a malignant soft tissue tumor in the deltoid muscle were retrospectively reviewed. The following items were evaluated: type of excision of the deltoid muscle, including total excision, subtotal excision, and partial excision; surgical margins; reconstruction procedure used; postoperative complications; local recurrence; metastasis; survival; and functional results (determined by the Musculoskeletal Tumor Society scoring system). RESULTS: After surgical resection, reconstruction in 6 of 8 patients was performed by pedicled latissimus dorsi musculocutaneous or muscle flap or pedicled trapezius musculocutaneous flap. Two patients did not undergo reconstruction because skin closure was possible. The partial excision group had a Musculoskeletal Tumor Society score of 100.0%, and the subtotal excision case and the total excision group had scores of 76.6% and 82.2%, respectively. None of the patients has demonstrated any evidence of local recurrence. CONCLUSION: We conclude that the functional results may depend on the volume of the excised deltoid muscle. Latissimus dorsi and trapezius musculocutaneous flaps were found to be useful for covering a defect of the deltoid muscle, although these flaps did not contribute to function of the shoulder.

A pilot project for the Japan arthroplasty register.

BACKGROUND: National arthroplasty registers are valuable tools for reporting on an updated epidemiologic survey of arthroplasties and for evaluating the performance of implants and operative procedures through the early identification of failure risk factors. More than ten registers have been launched globally, but no national register has been reported in Asia. METHODS: In February 2006, a pilot project of the Japan Arthroplasty Register (JAR) for total hip arthroplasty (THA) and total knee arthroplasty/unicompartmental knee arthroplasty (TKA/UKA) was launched by the Japanese Orthopaedic Association (JOA). Data obtained include information about patients, primary and revision arthroplasty operative procedures, and implants and materials used. The JAR office accumulated and processed all data and reports annually. RESULTS: Up to May 2011, 83 of 130 hospitals nominated by the JOA (64 %) participated in the JAR pilot project. From 2006 to 2011, 33,080 data collection forms were submitted; 17,534 for THA and 17,269 for TKA/UKA. A brief summary of the annual report of the JAR is available from The Japanese Society for Replacement Arthroplasty web site at http://jsra.info/ . CONCLUSION: A national arthroplasty register is a useful tool for evaluating the outcomes of interventions and the materials used in arthroplasties and for providing rapid feedback to practitioners and patients about any failure of THA and TKA/UKA. As the first national arthroplasty register in Asia, the JAR will help guide the development of registers of arthroplasty characteristics specific to Asian populations.

Comparison of the volar locking plate and the bridging external fixator in the treatment of distal radius fracture based on range of wrist motion assessed by functional radiography.

BACKGROUND: The authors hypothesized that an external fixator (EF) could compromise ROM compared with a volar locking plate (VP) because of the longer duration of immobilization using a VP. Postoperative ROM were therefore compared between the EF and the VP, focusing on the movement of the radiocarpal (RC) and midcarpal (MC) joints evident on radiology. The clinical outcomes of the two methods were also evaluated. MATERIAL/METHODS: Functional radiographs were taken in active volar and dorsal flexions from both the injured and contralateral sides. Clinical outcomes in terms of grip strength, pulp pinch, Quick-DASH, and the modified Cooney evaluation were compared. RESULTS: The average wrist volar flexion angle was significantly smaller on the injured side in both groups, significantly so in the VP group. No significant differences were seen in clinical outcome. Although distinct restriction of the wrist volar flexion angle was seen in patients treated with the VP, the Quick-DASH and the modified Cooney evaluation showed no difference between these two groups. CONCLUSIONS: These results should be considered when performing surgical treatment for patients with distal radius fracture. These procedures should be adopted to complement each other according to local conditions and individual patient-related factors.

Anatomic double-bundle anterior cruciate ligament reconstruction restores patellofemoral contact areas and pressures more closely than nonanatomic single-bundle reconstruction.

PURPOSE: To investigate the effects of anterior cruciate ligament (ACL) deficiency and nonanatomic single-bundle (SB) and anatomic double-bundle (DB) ACL reconstruction on the contact characteristics of the patellofemoral (PF) joint. METHODS: By use of a materials testing system, 7 fresh-frozen human cadaveric knees were tested. The following states were tested: ACL-intact knee, nonanatomic SB ACL reconstruction, anatomic DB ACL reconstruction, and ACL-deficient knee. Hamstring autografts were used. PF contact pressures and areas were measured with pressure-sensitive film at 30°, 60°, and 90° of knee flexion with a constant 100-N load on the quadriceps tendon. RESULTS: The total contact area of ACL-deficient and nonanatomic SB ACL-reconstructed knees (123.8 ± 63.9 and 149.6 ± 79.3 mm(2), respectively) significantly decreased when compared with those of the intact knee (206.1 ± 83.6 mm(2)) at 30° of knee flexion. The lateral-facet peak pressure of ACL-deficient and nonanatomic SB ACL-reconstructed knees (1.12 ± 0.52 and 1.22 ± 0.54 MPa, respectively) significantly decreased when compared with those of the intact knee (0.68 ± 0.38 MPa) at 90° of knee flexion. Anatomic DB ACL reconstruction restored the contact pressures and areas to values similar to those of the intact knee (no significant difference). CONCLUSIONS: ACL deficiency resulted in a significant decrease in the total and medial PF contact areas and in an increase in the lateral PF contact pressure. Anatomic DB ACL reconstruction more closely restored normal PF contact area and pressure than did nonanatomic SB ACL reconstruction. CLINICAL RELEVANCE: Our findings suggest that the changes in the PF contact area and pressures in ACL deficiency and after nonanatomic SB ACL reconstruction may be one of the causes of PF osteoarthritis or other related PF problems found at long-term follow-up. Anatomic DB ACL reconstruction may reduce the incidence of PF problems by closely restoring the contact area and pressure.

Clinical findings of hibernoma of the buttock and thigh: rare involvements and extremely high uptake of FDG-PET.

BACKGROUND: Hibernoma is a rare adipose tissue tumor of the soft tissue and the term is derived from the histological similarities to the brown fat found in hibernating animals. It usually occurs in the interscapular area, back, and neck and a few cases have been reported in the buttock or thigh. CASE REPORT: Two cases are presented, one of which had a lesion in the buttock and the other a lesion in the thigh. The lesion in the buttock extended into the pelvis. CT and MR findings suggested liposarcoma in both cases, but the uptake was extremely intense on 18F-FDG-PET in one case. This was not typical of liposarcoma and suggestive of hibernoma. Biopsy specimens revealed a proliferation of adipose cells with vacuolated granular eosinophilic cytoplasm. No cellular atypia or mitotic figures were observed in either case. A marginal excision was performed in one case and an intralesional excision in the other. There were no signs of local recurrence at the final follow-up. CONCLUSIONS: While occurrences in the buttock or thigh are exceedingly rare, hibernoma should be included in the differential diagnosis of an adipose tissue tumor in the thigh, even though the imaging findings mimic liposarcoma. 18F-FDG-PET may be a very meaningful technique to differentiate hibernoma from liposarcoma. A correct diagnosis should be established to prevent over-surgery.

TAS0728, A Covalent-binding, HER2-selective Kinase Inhibitor Shows Potent Antitumor Activity in Preclinical Models.

Activated HER2 is a promising therapeutic target for various cancers. Although several reports have described HER2 inhibitors in development, no covalent-binding inhibitor selective for HER2 has been reported. Here, we report a novel compound TAS0728 that covalently binds to HER2 at C805 and selectively inhibits its kinase activity. Once TAS0728 bound to HER2 kinase, the inhibitory activity was not affected by a high ATP concentration. A kinome-wide biochemical panel and cellular assays established that TAS0728 possesses high specificity for HER2 over wild-type EGFR. Cellular pharmacodynamics assays using MCF10A cells engineered to express various mutated HER2 genes revealed that TAS0728 potently inhibited the phosphorylation of mutated HER2 and wild-type HER2. Furthermore, TAS0728 exhibited robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors, thereby inducing apoptosis of HER2-amplified breast cancer cells and in tumor tissues of a xenograft model. TAS0728 induced tumor regression in mouse xenograft models bearing HER2 signal-dependent tumors and exhibited a survival benefit without any evident toxicity in a peritoneal dissemination mouse model bearing HER2-driven cancer cells. Taken together, our results demonstrated that TAS0728 may offer a promising therapeutic option with improved efficacy as compared with current HER2 inhibitors for HER2-activated cancers. Assessment of TAS0728 in ongoing clinical trials is awaited (NCT03410927).

Methods of reconstruction for bone defect after tumor excision: a review of alternatives.

Bone defect is a common problem encountered in the treatment of musculoskeletal tumor surgery. Allograft is a commonly used technique to reconstruct a large osseous defect following tumor excision in the United States and some European countries, and relatively good results have been reported because of its biologic nature. However, with the use of an allograft, there are concerns of transmission of infectious diseases, immunological reactions, and social or religious refusal in some regions in the world. Under these circumstances, vascularized autogenous fibular or iliac bone grafts are commonly used techniques and bone lengthening techniques using external fixation have been reported recently. These procedures utilize viable bone. In addition to these procedures, some biological reconstructive techniques utilizing nonviable bone have been performed as surgical alternatives for allografts using treated recycling bone including irradiated or pasteurized resected bone graft and reconstruction using an autograft containing tumor treated by liquid nitrogen. Although each technique has its proper advantages and disadvantages, the clinical results are similar to the allograft, and numerous techniques are now available as reasonable alternatives for allografts.

Effect of hyaluronic acid on the excursion resistance of tendon graft: a biomechanical in vitro study in a modified human model.

BACKGROUND: Adhesion between the tendon and tendon sheath after flexor tendon graft inhibits restoration of excursion and strength of the grafted tendons, so post-operative finger function is occasionally unsatisfactory. Early setting rehabilitation is one important factor to prevent the adhesion, and another factor may be a lubricant. We considered the possibility of utilizing hyaluronic acid as a lubricant. The goal of this study is to investigate the in vitro effect of hyaluronic acid on tendon excursion resistance against a digital pulley in a modified human model. METHODS: The excursion resistance between grafted intrasynovial and extrasynovial tendons and A2 pulley were evaluated, and compared before and after soaking in 10 mg/ml hyaluronic acid. FINDINGS: The resistance increased after extrasynovial tendon graft, and then it decreased after soaking hyaluronic acid solution. INTERPRETATION: The evidence we collected suggests that some style of administration of the hyaluronic acid might reduce the excursion resistance in the tendon-pulley unit, facilitating post-operative rehabilitation and limiting adhesion, after tendon graft and possibly improve the clinical outcome of flexor tendon graft.

A study of boron adsorption onto activated sludge.

Boron adsorption onto activated sludge was investigated using bench-scale reactors under simulated wastewater treatment conditions. Two experiments, continuous flow and batch, were performed. Boron concentrations were determined by means of inductively coupled plasma mass spectrometry. The results of the continuous-flow experiment indicated that a small amount of boron accumulated on the activated sludge and its concentration in the sludge depended on the nature of the biota in the sludge. Freundlich and Langmuir isotherm plots generated using the data from the batch experiment indicated that boron was adsorbed onto rather than absorbed into the sludge. The Freundlich constants, k and 1/n, were determined to be 26 mg/kg and 0.87. These values indicate that activated sludge has a limited capacity for boron adsorption and thus utilization of the excess sludge for farmland may not be toxic to plant at least boron concern.

Cell characterization of mononuclear and giant cells constituting pigmented villonodular synovitis.

The aim of this study was to determine the histologic and cellular characteristics of 2 cell types, mononuclear cells (Mos) and multinuclear giant cells (GCs), that predominantly constitute pigmented villonodular synovitis (PVS). Synovial tissues examined in this study were obtained from 10 patients with PVS. Five methods were used for cell analysis: (1) enzyme-histochemistry for tartrate-resistant acid phosphatase (TRAP); (2) immunohistochemistry using antibodies for CD68, macrophage colony-stimulating factor (M-CSF), MIB-1, p53, p21, p16, and cathepsin-L (cath L); (3) TdT-mediated deoxyuridine triphosphate-biotin terminal end labeling (TUNEL) as a measure of apoptosis; (4) fluorescence-based polymerase chain reaction single-strand conformation polymorphism analyses (FPCR-SSCP) to detect p53 gene mutations; and (5) in situ hybridization using gene-specific oligoprobes for matrix metalloproteinase (MMP)-2, MMP-9, receptor activator of nuclear factor kappaB ligand (RANKL), and calcitonin receptor (CTR). Both Mos and GCs were shown to express the macrophage/histiocyte marker CD68. In GCs, TRAP and CTR, both of which are known as characteristic phenotype markers of osteoclasts, were expressed. M-CSF and RANKL, which are together essential for osteoclast differentiation, were expressed in both Mos and GCs. Mos were shown to express MIB-1, but GCs were not. Although proliferation-suppressor proteins p53, p21, and p16 were expressed in both Mos and GCs, little apoptotic phenomenon of lining Mos was detected by TUNEL. In our study, p53 gene mutations for exons 5, 7, and 8 in PVS synovial tissues were not detected by FPCR-SSCP analysis. Furthermore, both types of cells demonstrated the proteolytic enzymes MMP-2 and MMP-9 mRNA, and cath L protein. These results suggest that PVS has a hyperplastic property consisting of the CD68-positive monocytic cell lineage with differentiation of osteoclastic giant cells from monocyte and probably controlled against proliferation by wild-type p53, p21, and p16.

Long-term variations in dissolved trace elements in the Sagami River and its tributaries (upstream area), Japan.

We investigated long-term variations in dissolved chemical species in water sampled from the Sagami River and its tributaries, Japan. The samples were taken monthly from May 1993 to April 2000 at 28 sampling sites in the Sagami River system. In this paper, we concentrate on 17 sites in the upper catchment. Twenty-four major to trace elements (Li, Mg, Al, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, As, Rb, Sr, Mo, Ag, Cd, Sb, Cs, Ba, W, Tl, Pb, U) were determined by using conventional Q-pole ICP-MS with direct nebulizalion. Water flux was measured from 1995. The data for most species were subjected to fast Fourier transformation (FFT) to extract dominant periodicities, their magnitudes, and their phases. Clear seasonal variations were observed for Al, V, As, Rb and Cs at some sampling points, especially in the tributaries. The seasonal variations may be due to either anthropogenic causes, such as irrigation or wastewater discharge, or natural causes, such as water temperature, pH, redox condition, water flux, or activity of microorganisms. We found no correlation with pH. Water temperature may not be a main controlling factor, although the seasonal variability would be correlated with it. Hydrologic factors may have only minor effects. We suggest that most of the seasonal variation might be correlated with the irrigation of rice paddies. It was difficult to identify all the causes of the seasonal variability. To investigate interannual trends, we used centered 12-month moving averages to eliminate seasonal variations. The water quality of the uppermost streams was generally constant, being controlled by springs on Mt. Fuji. However, in 1993 and 1998, V, As, Rb, Cs and U were depleted briefly, possibly by dilution by overflow from Lakes Kawaguchi and Yamanaka. Hydrologic factors may be more important for interannual variability than seasonal variability. Some heavy trace elements (Zn, Ni, Cd and Sb) showed very irregular variations with high concentration peaks. These elements were discharged from either factories or abandoned mine tailings.

Force on the sacrococcygeal and ischial areas during posterior pelvic tilt in seated posture.

BACKGROUND: Most posture problems encountered in persons who use wheelchairs in a seated posture for extended periods are related to sacral sitting due to posterior pelvic tilt. Posterior pelvic tilt places pressure and shearing force on the sacrococcygeal area that can lead to pressure ulcers, but the relationship between pelvic tilt and force applied to the sacrococcygeal and ischial tuberosity areas has not yet been investigated. OBJECTIVE: To investigate the relationships of posterior pelvic tilt in a seated posture with vertical force and horizontal force on the sacrococcygeal and ischial tuberosity areas. STUDY DESIGN: Repeated measures design. METHODS: Thirty male and female subjects aged ≥60 years sat in a measurement chair at varying pelvic tilt angles, and force on the sacrococcygeal and ischial tuberosity areas was measured. RESULTS: The pressure on the sacrococcygeal area increased with pelvic tilt in all subjects, with vertical force averaging 19% of the body weight at a pelvic tilt angle of 30°. The horizontal force on the sacrococcygeal area increased in 93% of the subjects, with an average increase equal to 3% of the body weight. CONCLUSIONS: We confirmed changes in vertical and horizontal forces on the sacrococcygeal and ischial tuberosity areas with a change in seated posture (pelvic tilt). CLINICAL RELEVANCE: We propose guidelines for rehabilitation practitioners working with wheelchair users to suggest improved ways of sitting in wheelchairs that avoid pelvic tilt angles that might promote pressure ulcers on the buttocks.

The concentrations of major and trace elements in rat kidney: aging effects and mutual relationships.

The concentrations of 26 major to trace elements in rat kidneys aging from 5 to 113 weeks old were determined. The rats investigated were the same rats used previously reported to have 29 elements in bones (femurs). The samples were decomposed by high purity nitric acid and hydrogen peroxide. Eight elements (Na, Mg, Si, P, K, Ca, Fe and Zn) were determined using inductively coupled plasma atomic emission spectrometry (ICP-AES) and 18 elements (Mn, Co, Ni, Cu, As, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Ba, Tl, Pb, Bi and U) were determined using inductively coupled plasma mass spectrometry (ICP-MS). The aging effects on the concentrations of these elements and mutual elemental relationships were investigated. Analysis of variance (ANOVA) for age variations indicated that the concentrations of P, K, Mn and Mo were almost constant across the age of rats (p>0.3). The concentration of many elements such as Na, Mg, Ca, Fe, Co, Cu, Zn, As, Se, Cd, Sn, Sb, Tl, Pb and Bi, showed significant increasing trends (p<0.01) with different patterns. Rubidium, Cs, Pb and Bi showed significant age variations but not monotonic trends. Silicon, Ni, Sr, Ba and U showed large concentration scatterings without any significant trends (p>0.01). The metabolism of these elements may not be well established in the kidney. Many toxic elements such as As, Cd, Sn, Pb and Bi showed a narrow concentration range among age-matched rats. The kidney may have established metabolic mechanisms to confine or accumulate these toxic elements even though their concentrations are very low (e.g., 10 ngg(-1) of Cd). These elements also closely coupled with Fe. A cluster analysis was performed using an elemental correlation matrix and indicated that these elements, including Fe, formed a cluster. However, another cluster analysis using "an aging effect eliminated" elemental correlation showed different clustering in which the Fe, Cd cluster disappeared.

Age-related effects of major and trace element concentrations in rat liver and their mutual relationships.

The concentrations of 22 major and trace elements in livers from rats aging from 5 to 113 weeks old were determined. The rats investigated were the same rats previously reported with respect to 29 elements in bones (femur) and 26 elements in kidneys. The samples were decomposed with high-purity nitric acid and hydrogen peroxide. Seven elements (Na, Mg, P, K, Ca, Fe and Zn) were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES), and 15 elements (Mn, Co, Cu, As, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Ba, Pb and Bi) were determined by inductively coupled plasma mass spectrometry (ICP-MS). Analysis of variance (ANOVA) for age variations indicated that the concentrations of many elements, such as Mg, P, K, Mn, Fe, Cu, Zn, Sr, Mo and Cd, were almost constant across the ages of the rats with the exception of 5 weeks old (p > 0.05). Arsenic, Pb and Bi showed significant increasing trends, while Na and Co showed decreasing trends (p < 0.01). Selenium showed a decreasing trend except at the initial stage of 5-9 weeks old. Calcium, Rb, Sn, Sb, Cs and Ba showed significant age-related variations, but their patterns were not monotonic. The liver clearly contrasts with the kidneys, in which many elements showed significant age-related variations with increasing trends. The concentration ranges of Mg, P, K, Mn, Cu, Zn, and Mo were controlled within 15% across all ages of rats. The homeostasis of the aforementioned elements may be well established in the liver. The toxic elements, such as Cd, Pb and Bi, showed a narrow concentration range among age-matched rats.

Interleukin-6 upregulates expression of ADAMTS-4 in fibroblast-like synoviocytes from patients with rheumatoid arthritis.

AIM: A disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS)-4 and ADAMTS-5 play crucial roles in the cleavage of aggrecan. Several recent studies have demonstrated the effect of cytokines such as interleukin (IL)-1ß, tumor necrosis factor-α and transforming growth factor-ß on the expression of ADAMTS-4 and ADAMTS-5 in fibroblast-like synoviocytes (FLS). However, the effect of IL-6 remains unclear. The aim of this study is to investigate the expression of ADAMTS-4 and ADAMTS-5 in FLS of rheumatoid arthritis (RA) patients after IL-6 stimulation. METHOD: Immunohistochemical staining was performed to examine the expression and localization of ADAMTS-4 and ADAMTS-5 in RA synovium. FLS isolated from RA patients were stimulated by IL-6 and soluble IL-6 receptor (sIL-6R) in the presence or absence of anti-IL-6R antibody, and the expression levels of ADAMTS-4 and ADAMTS-5 messenger RNA (mRNA) were assessed using real-time polymerase chain reaction. Furthermore, the IL-6 signaling pathway for regulation of ADAMTS-4 and ADAMTS-5 was also examined. RESULTS: Staining for ADAMTS-4 and ADAMTS-5 was mainly observed in the sublining layer of synovial membrane and pannus. The expression of ADAMTS-4 mRNA was increased by IL-6/sIL-6R, whereas that of ADAMTS-5 was decreased. Anti-IL-6R antibody suppressed the effect of IL-6/sIL-6R. Mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) kinase (MEK)1/2 inhibitor U0126 inhibited the effect of IL-6/sIL-6R on ADAMTS-4 mRNA expression in FLS. Signal transducer and activator of transcription 3 (STAT3) inhibitor parthenolide inhibited the effect of IL-6/sIL-6R on ADAMTS-4, and downregulated ADAMTS-5 expression. CONCLUSION: These results suggest IL-6 may participate in cartilage destruction in RA as an inducer of ADAMTS-4 expression from FLS.

Aging effects of major and trace elements in rat bones and their mutual correlations.

The concentrations of 29 major to trace elements in rat bones (femur) aging from 5 to 113 weeks old were determined. The samples were decomposed by high purity nitric acid and hydrogen peroxide. Nine elements (Na, Mg, P, K, Ca, Fe, Ni, Zn, and Sr) were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) and 20 elements (Li, B, Al, V, Cr, Mn, Cu, As, Se, Rb, Mo, Ag, Cd, Sb, Cs, Ba, W, Tl, Pb, and U) were determined by inductively coupled plasma mass spectrometry (ICP-MS). Aging effects on these elements and mutual elemental correlations were investigated. The concentrations of Ca, P and Na increased in the initial stage of 5-17 weeks and then maintained constant values, whereas those of Mg, K, Mn, Sr and Ba showed decreasing trends of differing patterns. Furthermore, Cu, Zn and Mo showed increasing trends for a whole range of ages. Selenium showed a remarkable increasing trend with a factor of 10. The values of Na, Mg, P, K, Ca, Mn, Cu, Zn, Se and Mo in the age-matched rats distributed narrow ranges, indicating that the metabolism of these elements in bone was well-established. By contrast, those of Al, V, Ni, Ag, Cd, Sb, W, Tl, and U were distributed across a broad range. The metabolism of these elements was not well-established. A cluster analysis was performed using an elemental correlation matrix.