Mid-term results of alumina ceramic unlinked total elbow arthroplasty with cement fixation for patients with rheumatoid arthritis.

Aims: The aim of this study was to report the mid-term clinical outcome of cemented unlinked J-alumina ceramic elbow (JACE) arthroplasties when used in patients with rheumatoid arthritis (RA). Patients and Methods: We retrospectively reviewed 87 elbows, in 75 patients with RA, which was replaced using a cemented JACE total elbow arthroplasty (TEA) between August 2003 and December 2012, with a follow-up of 96%. There were 72 women and three men, with a mean age of 62 years (35 to 79). The mean follow-up was nine years (2 to 14). The clinical condition of each elbow before and after surgery was assessed using the Mayo Elbow Performance Index (MEPI, 0 to 100 points). Radiographic loosening was defined as a progressive radiolucent line of >1 mm that was completely circumferential around the prosthesis. Results: The mean MEPI scores significantly improved from 40 (10 to 75) points preoperatively to 95 (30 to 100) points at final follow-up (p < 0.0001). Complications were noted in ten elbows (ten patients; 11%). Two had an intraoperative humeral fracture which was treated by fixation and united. One had a postoperative fracture of the olecranon which united with conservative treatment and one had a radial neuropathy which resolved. Further surgery was required for one with a dislocation, three with an ulnar neuropathy and one with a postoperative humeral fracture. Revision with removal of the components was performed in one elbow due to deep infection. There was no radiographic evidence of loosening around the components. With any revision surgery or revision with implant removal as the endpoint, the rates of survival up to 14 years were 93% (95% confidence interval (CI), 83.9 to 96.6) and 99% (95% CI 91.9 to 99.8), respectively, as determined by Kaplan-Meier analysis. Conclusion: With the appropriate indications, the mid-term clinical performance of the cemented JACE TEA is reliable and comparable to other established TEAs in the management of the elbow in patients with RA. Cite this article: Bone Joint J 2018;100-B:1066-73.

Proposal of patient-specific growth plate cartilage xenograft model for FGFR3 chondrodysplasia.

OBJECTIVE: FGFR3 chondrodysplasia is caused by a gain-of-function mutation of the FGFR3 gene. The disease causes abnormal growth plate cartilage and lacks effective drug treatment. We sought to establish an in vivo model for the study of FGFR3 chondrodysplasia pathology and drug testing. DESIGN: We created cartilage from human induced pluripotent stem cells (hiPSCs) and transplanted the cartilage into the subcutaneous spaces of immunodeficient mice. We then created cartilage from the hiPSCs of patients with FGFR3 chondrodysplasia and transplanted them into immunodeficient mice. We treated some mice with a FGFR inhibitor after the transplantation. RESULTS: Xenografting the hiPSC-derived cartilage reproduced human growth plate cartilage consisting of zones of resting, proliferating, prehypertrophic and hypertrophic chondrocytes and bone in immunodeficient mice. Immunohistochemistry of xenografts using anti-human nuclear antigen antibody indicated that all chondrocytes in growth plate cartilage were human, whereas bone was composed of human and mouse cells. The pathology of small hypertrophic chondrocytes due to up-regulated FGFR3 signaling in FGFR3 skeletal dysplasia was recapitulated in growth plate cartilage formed in the xenografts of patient-specific hiPSC-derived cartilage. The mean diameters of hypertrophic chondrocytes between wild type and thanatophoric dysplasia were significantly different (95% CI: 13.2-26.9; n = 4 mice, one-way analysis of variance (ANOVA)). The pathology was corrected by systemic administration of a FGFR inhibitor to the mice. CONCLUSION: The patient-specific growth plate cartilage xenograft model for FGFR3 skeletal dysplasia indicated recapitulation of pathology and effectiveness of a FGFR inhibitor for treatment and warrants more study for its usefulness to study disease pathology and drug testing.

Medial meniscus posterior root tear induces pathological posterior extrusion of the meniscus in the knee-flexed position: An open magnetic resonance imaging analysis.

BACKGROUND: A medial meniscus posterior root tear (MMPRT) is defined as an injury to the posterior meniscal insertion on the tibia. In MMPRT, the medial meniscus (MM) hoop function is damaged, and the MM undergoes a medial extrusion into the interior from the superior articular surface of the tibia. However, the details of MM position and movement during knee joint movement are unclear in MMPRT cases. The present study aims to evaluate MM position and movement via magnetic resonance imaging (MRI) examination of the MM posterior extrusion (MMPE) at knee flexion angles of 10° and 90°. We hypothesized that, during knee flexion, the MM will shift to the posterior and the posterior extrusion will increase compared to that when the knee is extended. MATERIALS AND METHODS: Twenty-four patients were diagnosed with symptomatic MMPRT on open MRI examination. Preoperative MMPE, anteroposterior interval (API) of the MM, and MM medial extrusion (MMME) at knee flexion angles of 10° and 90° were measured. RESULTS: For patients with MMPRT, the MMPE increased from -4.77±1.43mm to 3.79±1.17mm (p<0.001) when the knee flexion angle increased from 10° to 90°. Further, flexing the knee from 10° to 90° decreased the API of the MM from 20.19±4.22mm to 16.41±5.14mm (p<0.001). MMME showed no significant change between knee flexion angles of 10° and 90°. DISCUSSION: This study demonstrated that, in cases of MMPRT, the MMPE clearly increases when the knee is flexed to 90°, while MMME does not change. Our results suggest that open MRI examination can be used to evaluate the dynamic position of the posterior MM by scanning the knee as it flexes to 90°. LEVEL OF EVIDENCE: IV: retrospective cohort study.

Medial meniscus extrusion correlates with disease duration of the sudden symptomatic medial meniscus posterior root tear.

INTRODUCTION: Medial meniscus posterior root tear (MMPRT) leads to abnormal biomechanics of the knee by inducing the medial meniscus extrusion (MME). However, a time-dependent increase of the MME is not fully elucidated in patients suffering from the acute MMPRT. The aim of this study was to investigate the relationships among disease duration of the MMPRT and severity of the MME. We hypothesized that MME measurement correlates with disease duration after a sudden onset of the minor traumatic MMPRT during the short-term follow-up period. MATERIALS AND METHODS: Forty-six patients who had an accurate episode of the posteromedial painful popping were investigated. All the patients were diagnosed having a symptomatic MMPRT with magnetic resonance imaging (MRI) examinations. Absolute MME was measured using MRI scans within 12 months after painful popping events. A correlation coefficient between duration from injury to MRI examination and absolute MME was evaluated. RESULTS: Mean absolute MME was 4.5±1.6mm (range, 1.1-8.8mm) on MRI measurements. A good correlation was observed between MME measurement and duration from injury to MRI examination (R2=0.612). The best-fit equation for predicting each value was: MME=0.014×disease duration+3.288mm. DISCUSSION: This study demonstrated that absolute MME increases progressively within the short duration after the onset of symptomatic MMPRT. Our results suggest that preoperative MME assessment may be important in determining disease duration and treatment strategy of the MMPRT. LEVEL OF EVIDENCE: Retrospective cohort study level IV.

A new aiming guide can create the tibial tunnel at favorable position in transtibial pullout repair for the medial meniscus posterior root tear.

INTRODUCTION: Injuries to the medial meniscus (MM) posterior root lead to accelerated cartilage degeneration of the knee. An anatomic placement of the MM posterior root attachment is considered to be critical in transtibial pullout repair of the medial meniscus posterior root tear (MMPRT). However, tibial tunnel creation at the anatomic attachment of the MM posterior root is technically difficult using a conventional aiming device. The aim of this study was to compare two aiming guides. We hypothesized that a newly-developed guide, specifically designed, creates the tibial tunnel at an adequate position rather than a conventional device. MATERIALS AND METHODS: Twenty-six patients underwent transtibial pullout repairs. Tibial tunnel creation was performed using the Multi-use guide (8 cases) or the PRT guide that had a narrow twisting/curving shape (18 cases). Three-dimensional computed tomography images of the tibial surface were evaluated using the Tsukada's measurement method postoperatively. Expected anatomic center of the MM posterior root attachment and tibial tunnel center were evaluated using the percentage-based posterolateral location on the tibial surface. Percentage distance between anatomic center and tunnel center was calculated. RESULTS: Anatomic center of the MM posterior root footprint located at a position of 78.5% posterior and 39.4% lateral. Both tunnels were anteromedial but tibial tunnel center located at a more favorable position in the PRT group: percentage distance was significantly smaller in the PRT guide group (8.7%) than in the Multi-use guide group (13.1%). DISCUSSION: The PRT guide may have great advantage to achieve a more anatomic location of the tibial tunnel in MMPRT pullout repair. LEVEL OF EVIDENCE: III.

Pullout repair of a medial meniscus posterior root tear using a FasT-Fix® all-inside suture technique.

A medial meniscus posterior root tear (MMPRT) may increase the tibiofemoral contact pressure by decreasing the tibiofemoral contact area. Meniscal dysfunction induced by posterior root injury may lead to the development of osteoarthritic knees. Repair of a MMPRT can restore medial meniscus (MM) function and prevent knee osteoarthritis progression. Several surgical procedures have been reported for treating a MMPRT. However, these procedures are associated with several technical difficulties. Here, we describe a technique to stabilize a torn MM posterior root using the FasT-Fix® all-inside meniscal suture device and a new aiming device. The uncut free-end of the FasT-Fix® suture can be used as a thread for transtibial pullout repair. Our procedure might help overcome the technical difficulties in arthroscopic treatment of a MMPRT.

Improvement of gemcitabine sensitivity of p53-mutated pancreatic cancer MiaPaCa-2 cells by RUNX2 depletion-mediated augmentation of TAp73-dependent cell death.

Pancreatic cancer exhibits the worst prognostic outcome among human cancers. Recently, we have described that depletion of RUNX2 enhances gemcitabine (GEM) sensitivity of p53-deficient pancreatic cancer AsPC-1 cells through the activation of TAp63-mediated cell death pathway. These findings raised a question whether RUNX2 silencing could also improve GEM efficacy on pancreatic cancer cells bearing p53 mutation. In the present study, we have extended our study to p53-mutated pancreatic cancer MiaPaCa-2 cells. Based on our current results, MiaPaCa-2 cells were much more resistant to GEM as compared with p53-proficient pancreatic cancer SW1990 cells, and there existed a clear inverse relationship between the expression levels of TAp73 and RUNX2 in response to GEM. Forced expression of TAp73α in MiaPaCa-2 cells significantly promoted cell cycle arrest and/or cell death, indicating that a large amount of TAp73 might induce cell death even in the presence of mutant p53. Consistent with this notion, overexpression of TAp73α stimulated luciferase activity driven by p53/TAp73-target gene promoters in MiaPaCa-2 cells. Similar to AsPC-1 cells, small interfering RNA-mediated knockdown of RUNX2 remarkably enhanced GEM sensitivity of MiPaCa-2 cells. Under our experimental conditions, TAp73 further accumulated in RUNX2-depleted MiaPaCa-2 cells exposed to GEM relative to GEM-treated non-silencing control cells. As expected, silencing of p73 reduced GEM sensitivity of MiPaCa-2 cells. Moreover, GEM-mediated Tyr phosphorylation level of TAp73 was much more elevated in RUNX2-depleted MiaPaCa-2 cells. Collectively, our present findings strongly suggest that knockdown of RUNX2 contributes to a prominent enhancement of GEM sensitivity of p53-mutated pancreatic cancer cells through the activation of TAp73-mediated cell death pathway, and also provides a promising strategy for the treatment of patients with pancreatic cancer bearing p53 mutation.

The figure-of-nine leg position for anatomic anterior cruciate ligament reconstruction.

Anatomic double-bundle anterior cruciate ligament (ACL) reconstruction can restore the function and kinematics of the knee in ACL-deficient patients. Several outside-in drilling systems for accurate femoral tunnel creations have been developed. However, the femoral tunnel creation at the lower position of the intercondylar notch can be difficult in a usual leg position with the knee flexed at 90° without varus stress. This technical note describes that the figure-of-nine leg position provides a better arthroscopic view to safely clean up the ACL femoral footprint located at the lower area of the lateral intercondylar wall. This position is useful to create the optimal femoral tunnels using the outside-in drilling technique, without damaging the lateral meniscus posterior root, lateral tibial eminence, and supplemental fibers that bridge the gap between the lateral meniscus and the ACL tibial insertion.

Silencing of RUNX2 enhances gemcitabine sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the stimulation of TAp63-mediated cell death.

Runt-related transcription factor 2 (RUNX2) has been considered to be one of master regulators for osteoblast differentiation and bone formation. Recently, we have described that RUNX2 attenuates p53/TAp73-dependent cell death of human osteosarcoma U2OS cells bearing wild-type p53 in response to adriamycin. In this study, we have asked whether RUNX2 silencing could enhance gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells. Under our experimental conditions, GEM treatment increased the expression level of p53 family TAp63, whereas RUNX2 was reduced following GEM exposure, indicating that there exists an inverse relationship between the expression level of TAp63 and RUNX2 following GEM exposure. To assess whether TAp63 could be involved in the regulation of GEM sensitivity of AsPC-1 cells, small interfering RNA-mediated knockdown of TAp63 was performed. As expected, silencing of TAp63 significantly prohibited GEM-dependent cell death as compared with GEM-treated non-silencing cells. As TAp63 was negatively regulated by RUNX2, we sought to examine whether RUNX2 knockdown could enhance the sensitivity to GEM. Expression analysis demonstrated that depletion of RUNX2 apparently stimulates the expression of TAp63, as well as proteolytic cleavage of poly ADP ribose polymerase (PARP) after GEM exposure, and further augmented GEM-mediated induction of p53/TAp63-target genes, such as p21 (WAF1) , PUMA and NOXA, relative to GEM-treated control-transfected cells, implying that RUNX2 has a critical role in the regulation of GEM resistance through the downregulation of TAp63. Notably, ablation of TAp63 gave a decrease in number of γH2AX-positive cells in response to GEM relative to control-transfected cells following GEM exposure. Consistently, GEM-dependent phosphorylation of ataxia telangiectasia-mutated protein was remarkably impaired in TAp63 knockdown cells. Collectively, our present findings strongly suggest that RUNX2-mediated repression of TAp63 contributes at least in part to GEM resistance of AsPC-1 cells, and thus silencing of RUNX2 may be a novel strategy to enhance the efficacy of GEM in p53-deficient pancreatic cancer cells.

Receptor-type protein tyrosine phosphatase κ directly dephosphorylates CD133 and regulates downstream AKT activation.

Although CD133 has been considered to be a molecular marker for cancer stem cells, its functional roles in tumorigenesis remain unclear. We here examined the molecular basis behind CD133-mediated signaling. Knockdown of CD133 resulted in the retardation of xenograft tumor growth of colon cancer-derived HT-29 and LoVo cells accompanied by hypophosphorylation of AKT, which diminished ß-catenin/T-cell factor-mediated CD44 expression. As tyrosine residues of CD133 at positions 828 and 852 were phosphorylated in HT-29 and SW480 cells, we further addressed the significance of this phosphorylation in the tumorigenesis of SW480 cells expressing mutant CD133, with substitution of these tyrosine residues by glutamate (CD133-EE) or phenylalanine (CD133-FF). Forced expression of CD133-EE promoted much more aggressive xenograft tumor growth relative to wild-type CD133-expressing cells accompanied by hyperphosphorylation of AKT; however, CD133-FF expression had negligible effects on AKT phosphorylation and xenograft tumor formation. Intriguingly, the tyrosine phosphorylation status of CD133 was closely linked to the growth of SW480-derived spheroids. Using yeast two-hybrid screening, we finally identified receptor-type protein tyrosine phosphatase κ (PTPRK) as a binding partner of CD133. In vitro studies demonstrated that PTPRK associates with the carboxyl-terminal region of CD133 through its intracellular phosphatase domains and also catalyzes dephosphorylation of CD133 at tyrosine-828/tyrosine-852. Silencing of PTPRK elevated the tyrosine phosphorylation of CD133, whereas forced expression of PTPRK reduced its phosphorylation level markedly and abrogated CD133-mediated AKT phosphorylation. Endogenous CD133 expression was also closely associated with higher AKT phosphorylation in primary colon cancer cells, and ectopic expression of CD133 enhanced AKT phosphorylation. Furthermore, lower PTPRK expression significantly correlated with the poor prognosis of colon cancer patients with high expression of CD133. Thus, our present findings strongly indicate that the tyrosine phosphorylation of CD133, which is dephosphorylated by PTPRK, regulates AKT signaling and has a critical role in colon cancer progression.

Plasma CD147 reflects histological features in patients with lupus nephritis.

OBJECTIVE: A glycosylated transmembrane protein, CD147, has been implicated in regulating lymphocyte responsiveness and leukocyte recruitment. As lupus nephritis (LN) often follows a relapsing-remitting disease course, accurate understanding of the disease activity would be extremely helpful in improving prognosis. Unfortunately, neither clinical nor serological data can accurately reflect the histological features of LN. The present study investigated whether CD147 can accurately predict pathological features of LN. METHODS: Plasma and spot urine samples were collected from 64 patients who underwent renal biopsy between 2008 and 2011. Disease activity for LN tissues was evaluated using the biopsy activity index, and compared to levels of biomarkers including CD147. RESULTS: In LN tissues, CD147 induction was striking in injured glomeruli and infiltrating inflammatory cells, but not in damaged tubules representing atrophy. Plasma CD147 levels accurately reflected the histological disease activity. However, prediction using a single molecule would be quite difficult because of the complex pathogenesis of LN. The diagnostic accuracy of multiplex parameters indicated that the combination including plasma CD147 might yield excellent diagnostic abilities for guiding ideal LN therapy. CONCLUSION: Plasma CD147 levels might offer useful insights into disease activity as a crucial biomarker in patients with LN.

Favorable outcome after complete resection in elderly soft tissue sarcoma patients: Japanese Musculoskeletal Oncology Group study.

BACKGROUND: The surgical management of soft tissue sarcoma (STS) in elderly patients has only been addressed in a few studies. The objective of the current study was to assess surgical outcomes in patients with STS aged 70 years and older and the association of older age with the survival after complete resection. METHODS: A retrospective analysis was conducted in 158 elderly patients with localized STS who visited 11 institutions participating in Japanese Musculoskeletal Oncology Group between 1995 and 2006 and were treated by surgical resection. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Median follow-up period was 38 months. Histologically high-grade tumors were detected in 71% of the patients. Wide resection with adequate margins was performed in 66% of the cases. Systemic chemotherapy was performed in only 5 patients. Univariate analysis identified histological grade and gender as statistically significant prognostic factors for sarcoma-specific survival. Multivariate analysis did not identify significant prognostic factors for sarcoma-specific survival, although high grade sarcoma emerged as a potentially significant prognostic factor (P = 0.050). Local recurrence was detected in 19% of the patients. Multivariate analysis of local recurrence-free survival showed that tumor site and surgical margins were statistically significant prognostic factors. CONCLUSIONS: Older age was not identified as a prognostic factor for sarcoma-specific survival, which is not consistent with the findings of previous studies showing that older age was associated with decreased sarcoma-specific survival. Complete resection should be indicated and can lead to optimal treatment outcome for properly selected elderly patients.

Runt-related transcription factor 2 (RUNX2) inhibits p53-dependent apoptosis through the collaboration with HDAC6 in response to DNA damage.

Runt-related transcription factor 2 (RUNX2) is the best known as an essential protein for osteoblast differentiation. In this study, we have found for the first time that RUNX2 acts as a negative regulator for p53 in response to DNA damage. On DNA damage mediated by adriamycin (ADR) exposure, p53 as well as RUNX2 was induced at protein and mRNA level in human osteosarcoma-derived U2OS cells in association with a significant upregulation of various p53-target genes. Indirect immunostaining and co-immunoprecipitation experiments demonstrated that RUNX2 colocalizes with p53 in cell nucleus and forms a complex with p53 following ADR treatment. Chromatin immunoprecipitation assays revealed that RUNX2/p53 complex is efficiently recruited onto p53-target promoters in response to ADR, suggesting that RUNX2 might be involved in the regulation of transcriptional activation mediated by p53. Indeed, forced expression of RUNX2 resulted in a remarkable downregulation of p53-target genes. Consistent with these observations, knockdown of RUNX2 enhanced ADR-mediated apoptosis and also elevated p53-target gene expression in response to ADR. On the other hand, depletion of RUNX2 in p53-deficient human lung carcinoma-derived H1299 cells had an undetectable effect on p53-target gene expression regardless of ADR treatment, indicating that RUNX2-mediated downregulation of p53-target genes is dependent on p53. Furthermore, RUNX2/p53 complex included histone deacetylase 6 (HDAC6) and HDAC6 was also recruited onto p53-target promoters following ADR exposure. Of note, HDAC6-specific chemical inhibitor tubacin treatment enhanced ADR-mediated upregulation of p53-target gene expression, indicating that deacetylase activity of HDAC6 is required for RUNX2-mediated downregulation of p53-target gene. Taken together, our present findings strongly suggest that RUNX2 inhibits DNA damage-induced transcriptional as well as pro-apoptotic activity of p53 through the functional collaboration with HDAC6 and therefore might be an attractive therapeutic target for cancer treatment.

A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus.

Adenovirus serotype 5 (Ad5) is frequently used as an effective vector for induction of therapeutic transgenes in cancer gene therapy or of tumor cell lysis in oncolytic virotherapy. Ad5 can infect target cells through binding with the coxsackie and adenovirus receptor (CAR). Thus, the infectious ability of Ad5-based vectors depends on the CAR expression level in target cells. There are conventional methods to evaluate the CAR expression level in human target cells, including flow cytometry, western blotting and immunohistochemistry. Here, we show a simple system for detection and assessment of functional CAR expression in human tumor cells, using the green fluorescent protein (GFP)-expressing telomerase-specific replication-competent adenovirus OBP-401. OBP-401 infection induced detectable GFP expression in CAR-expressing tumor cells, but not in CAR-negative tumor cells, nor in CAR-positive normal fibroblasts, 24 h after infection. OBP-401-mediated GFP expression was significantly associated with CAR expression in tumor cells. OBP-401 infection detected tumor cells with low CAR expression more efficiently than conventional methods. OBP-401 also distinguished CAR-positive tumor tissues from CAR-negative tumor and normal tissues in biopsy samples. These results suggest that GFP-expressing telomerase-specific replication-competent adenovirus is a very potent diagnostic tool for assessment of functional CAR expression in tumor cells for Ad5-based antitumor therapy.

Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes.

OBJECTIVE: To investigate the inhibitory effects and the regulatory mechanisms of histone deacetylase (HDAC) inhibitors on mechanical stress-induced gene expression of runt-related transcription factor (RUNX)-2 and adisintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 in human chondrocytes. METHODS: Human chondrocytes were seeded in stretch chambers at a concentration of 5 × 10(4)cells/chamber. Cells were pre-incubated with or without HDAC inhibitors (MS-275 or trichostatin A; TSA) for 12h, followed by uniaxial cyclic tensile strain (CTS) (0.5Hz, 10% elongation), which was applied for 30 min using the ST-140-10 system (STREX, Osaka, Japan). Total RNA was extracted and the expression of RUNX-2, ADAMTS-5, matrix metalloproteinase (MMP)-3, and MMP-13 at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The activation of diverse mitogen-activated protein kinase (MAPK) pathways with or without HDAC inhibitors during CTS was examined by western blotting. RESULTS: HDAC inhibitors (TSA: 10 nM, MS-275: 100 nM) suppressed CTS-induced expression of RUNX-2, ADAMTS-5, and MMP-3 at both the mRNA and protein levels within 1h. CTS-induced activation of p38 MAPK (p38), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) MAPKs was downregulated by both HDAC inhibitors. CONCLUSION: The CTS-induced expression of RUNX-2 and ADAMTS-5 was suppressed by HDAC inhibitors via the inhibition of the MAPK pathway activation in human chondrocytes. The results of the current study suggested a novel therapeutic role for HDAC inhibitors against degenerative joint disease such as osteoarthritis.

Carrier density dependence of the nonlinear absorption of intense THz radiation in GaAs.

We study the carrier density dependence of nonlinear terahertz (THz) absorption due to field-induced intervalley scattering in photoexcited GaAs using the optical-pump/THz-probe technique. The intervalley scattering in GaAs is strongly dependent on the photo-carrier density. As the carrier density is increased from 1 × 10(17) to 4.7 × 10(17) cm(-3), the nonlinear absorption bleaching increases. However, if the carrier density is increased further above 4.7 × 10(17) cm(-3), the trend reverses and the bleaching is reduced. The initial increase in absorption bleaching is because, unlike low THz field, high THz field experiences intervalley scattering and nonparabolicity of the conduction band. On the other hand, a simple electron transport model shows that the reduction in intervalley scattering is mainly due to the increase in the electron-hole scattering rate with the increase in the carrier density. This increase in the electron-hole scattering rate limits the maximum kinetic energy attainable by the electrons and thus reduces the observed nonlinear absorption.

A novel oncogenic pathway by TLS-CHOP involving repression of MDA-7/IL-24 expression.

BACKGROUND: Translocated in liposarcoma-CCAAT/enhancer binding protein homologous protein (TLS-CHOP) (also known as FUS-DDIT3) chimeric oncoprotein is found in the majority of human myxoid liposarcoma (MLS), but its molecular function remains unclear. METHODS: We knockdowned TLS-CHOP expression in MLS-derived cell lines by a specific small interfering RNA, and analysed the gene expression profiles with microarray. RESULTS: TLS-CHOP knockdown inhibited growth of MLS cells, and induced an anticancer cytokine, melanoma differentiation-associated gene 7 (MDA-7)/interleukin-24 (IL-24) expression. However, double knockdown of TLS-CHOP and MDA-7/IL-24 did not inhibit MLS cell growth. CONCLUSION: Repression of MDA-7/IL-24 expression by TLS-CHOP is required for MLS tumour growth, and TLS-CHOP may become a promising therapeutic target for MLS treatment.

Quantifying the uncertainty of spontaneous Ca2+ oscillations in astrocytes: particulars of Alzheimer's disease.

The quantification of spontaneous calcium (Ca(2+)) oscillations (SCOs) in astrocytes presents a challenge because of the large irregularities in the amplitudes, durations, and initiation times of the underlying events. In this article, we use a stochastic context to account for such SCO variability, which is based on previous models for cellular Ca(2+) signaling. First, we found that passive Ca(2+) influx from the extracellular space determine the basal concentration of this ion in the cytosol. Second, we demonstrated the feasibility of estimating both the inositol 1,4,5-trisphosphate (IP(3)) production levels and the average number of IP(3) receptor channels in the somatic clusters from epifluorescent Ca(2+) imaging through the combination of a filtering strategy and a maximum-likelihood criterion. We estimated these two biophysical parameters using data from wild-type adult mice and age-matched transgenic mice overexpressing the 695-amino-acid isoform of human Alzheimer ß-amyloid precursor protein. We found that, together with an increase in the passive Ca(2+) influx, a significant reduction in the sensitivity of G protein-coupled receptors might lie beneath the abnormalities in the astrocytic Ca(2+) signaling, as was observed in rodent models of Alzheimer's disease. This study provides new, to our knowledge, indices for a quantitative analysis of SCOs in normal and pathological astrocytes.

Anterior transposition of the ulnar nerve with endoscopic assistance.

We treated 20 patients with cubital tunnel syndrome by anterior transposition of the ulnar nerve with endoscopic assistance. Five elbows were classified preoperatively as McGowan's stage 1, 11 as stage 2 and four as stage 3. Excellent outcomes were obtained in nine and good in eight patients. Three patients had fair results. Improvement of symptoms occurred in all patients. There were no serious complications. All ulnar nerves remained anteriorly transposed.