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Mycobacterium tuberculosis(Mtb) infects cells in multiple lung myeloid cell subsets and causes chronic infection despite innate and adaptive immune responses. However, the mechanisms allowing Mtb to evade elimination are not fully understood. Here, using new methods, we determined that after T cell responses have developed, CD11clomonocyte-derived lung cells termed MNC1 (mononuclear cell subset 1), harbor more live Mtb compared to alveolar macrophages (AM), neutrophils, and less permissive CD11chiMNC2. Bulk RNA sequencing of sorted cells revealed that the lysosome biogenesis pathway is underexpressed in MNC1. Functional assays confirmed that Mtb-permissive MNC1 have less lysosome content, acidification, and proteolytic activity than AM, and less nuclear TFEB, a master regulator of lysosome biogenesis. Mtb infection does not drive lysosome deficiency in MNC1 in vivo. Instead, Mtb recruits MNC1 and MNC2 to the lungs for its spread from AM to these cell subsets as a virulence mechanism that requires the Mtb ESX-1 secretion system. The c-Abl tyrosine kinase inhibitor nilotinib activates TFEB and enhances lysosome function of primary macrophages in vitro and MNC1 and MNC2 in vivo, improving control of Mtb infection. Our results indicate that Mtb exploits lysosome-poor monocyte-derived cells for in vivo persistence, suggesting a potential target for host-directed tuberculosis therapy.One Sentence SummaryVirulent Mtb recruits and exploits intrinsically lysosome-deficient lung mononuclear cell subsets to resist elimination during chronic infection.

Several immunotherapy approaches that mobilize CD8+ T cell responses stimulate tumor rejection, and some, such as checkpoint blockade, have been approved for several cancer indications and show impressive increases in patient survival. However, tumors may evade CD8+ T cell recognition via loss of MHC molecules or because they contain few or no neoantigens. Therefore, approaches are needed to combat CD8+ T cell-resistant cancers. STING-activating cyclic dinucleotides (CDNs) are a new class of immune-stimulating agents that elicit impressive CD8+ T cell-mediated tumor rejection in preclinical tumor models and are now being tested in clinical trials. Here, we demonstrate powerful CDN-induced, natural killer (NK) cell-mediated tumor rejection in numerous tumor models, independent of CD8+ T cells. CDNs enhanced NK cell activation, cytotoxicity, and antitumor effects in part by inducing type I interferon (IFN). IFN acted in part directly on NK cells in vivo and in part indirectly via the induction of IL-15 and IL-15 receptors, which were important for CDN-induced NK activation and tumor control. After in vivo administration of CDNs, dendritic cells (DCs) up-regulated IL-15Rα in an IFN-dependent manner. Mice lacking the type I IFN receptor specifically on DCs had reduced NK cell activation and tumor control. Therapeutics that activate NK cells, such as CDNs, checkpoint inhibitors, NK cell engagers, and cytokines, may represent next-generation approaches to cancer immunotherapy.

Objectives: Menopausal transition in women initiates with declining estrogen levels and is followed by significant changes in their physiological characteristics. These changes often lead to medical conditions, such as obesity, which is correlated with chronic low-grade/subclinical inflammation. Ocimum gratissimum L. is a food spice or traditional herb in many countries; the plant is rich in antioxidants, which possess anti-inflammation activities and multitude of other therapeutic functions. Methods: In this study, we evaluated effects of O. gratissimum extract (OGE) in preventing obesity by using ovariectomized (OVX) animal models to mimic menopausal women. Methods: OVX rats showed increase in body weight and in adipocyte size in perigonadal adipose tissue (p

Several immunotherapy approaches that mobilize CD8(+) T cell responses stimulate tumor rejection, and some, such as checkpoint blockade, have been approved for several cancer indications and show impressive increases in patient survival. However, tumors may evade CD8(+) T cell recognition via loss of MHC molecules or because they contain few or no neoantigens. Therefore, approaches are needed to combat CD8(+) T cell-resistant cancers. STING-activating cyclic dinucleotides (CDN) are a new class of immune-stimulating agents that elicit impressive CD8(+) T cell-mediated tumor rejection in preclinical tumor models and are now being tested in clinical trials. Here we demonstrate powerful CDN-induced, natural killer (NK) cell-mediated tumor rejection in numerous tumor models, independent of CD8(+) T cells. CDNs enhanced NK cell activation, cytotoxicity, and antitumor effects in part by inducing type I IFN (IFN). IFN acted in part directly on NK cells in vivo, and in part indirectly via the induction of IL-15 and IL-15 receptors, which were important for CDN-induced NK activation and tumor control. After in vivo administration of CDNs, dendritic cells (DCs) upregulated IL-15Rα in an IFN-dependent manner. Mice lacking the type I IFN receptor specifically on DCs had reduced NK cell activation and tumor control. Therapeutics that activate NK cells, such as CDNs, checkpoint inhibitors, NK cell engagers, and cytokines, may represent next-generation approaches to cancer immunotherapy.

M. tuberculosis (Mtb) infects lung phagocytes including alveolar macrophages (AM) and recruited/monocyte-derived macrophages (RM). However, little is known about the distinct roles of different cell subsets in Mtb persistence, and how they differ in controlling Mtb during chronic infection. Using fluorescent reporter strains and quantitation of live bacteria by cfu plating of sorted cell subsets, we found that AM are superior to RM in restricting and killing Mtb during chronic infection (4 wk PI). Subsequent bulk RNA-Seq of live-sorted cells from infected mice reveal that genes of the lysosome pathway are under-expressed in RM compared with AM. Using functional assays, we show here that RM have poorer lysosome function than AM. Specifically, AM not only have more lysosome content, more abundant lysosomal enzyme content and activities, but also have higher expression of proteins for lysosome acidification and more acidic lysosomes. Moreover, immunofluorescence data reveal that AM have more nuclear TFEB than RM. Nuclear translocation activates TFEB, which serves as a master regulator of lysosome biogenesis. We also found that TFEB overexpressing bone marrow-derived macrophages have enhanced abilities to kill virulent Mtb. Together, these results imply that TFEB may drive the difference of lysosome functions between AM and RM, leading to the difference in killing Mtb, and that Mtb takes advantage of intrinsically lysosome-poor RM for persistence.

Objectives: Menopausal transition with declining estrogen levels significantly affects the physiological properties of women and consequently contributes to a series of medical conditions, including obesity. Obesity is a crucial risk factor associated with cardiovascular diseases, diabetes mellitus, and breast cancer. Increasing dietary protein content improves satiety and energy expenditure. Thus, we hypothesize that supplementing with collagen, a common dietary protein, may alleviate menopause-induced obesity. Methods: We used ovariectomized (OVX) rats to mimic a menopausal human. The body weight of OVX rats significantly increased compared with that of sham-operated rats (P

In the past decade, no significant improvement has been made in chemotherapy for osteosarcoma (OS). To develop improved agents against OS, we screened 70 species of medicinal plants and treated two human OS cell lines with different agent concentrations. We then examined cell viability using the MTT assay. Results showed that a candidate plant, particularly the rhizomes of Anemone altaica Fisch. ex C. A. Mey aqueous extract (AAE), suppressed the viability of HOS and U2OS cells in a concentration-dependent manner. Flow cytometry analysis revealed that AAE significantly increased the amount of cell shrinkage (Sub-G1 fragments) in HOS and U2OS cells. Moreover, AAE increased cytosolic cytochrome c and Bax, but decreased Bcl-2. The amount of cleaved caspase-3 and poly-(ADP-ribose) polymerase-1 (PARP-1) were significantly increased. AAE suppressed the growth of HOS and U2OS through the intrinsic apoptotic pathway. Data suggest that AAE is cytotoxic to HOS and U2OS cells and has no significant influence on human osteoblast hFOB cells. The high mRNA levels of apoptosis-related factors (PPP1R15A, SQSTM1, HSPA1B, and DDIT4) and cellular proliferation markers (SKA2 and BUB1B) were significantly altered by the AAE treatment of HOS and U2OS cells. Results show that the anticancer activity of AAE could up-regulate the expression of a cluster of genes, especially those in the apoptosis-related factor family and caspase family. Thus, AAE has great potential as a useful therapeutic drug for human OS.

Background: Advanced glycation end-products (AGEs) can accumulate in organs and tissues during ageing and diabetes. Increased levels of AGEs are found in the bone tissue of patients with osteoporosis. The purpose of this study was to evaluate circulating AGEs in patients with osteoporosis. Methods: We evaluated plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43 healthy women without osteoporosis or osteopenia. Results: Higher levels of serum AGEs were found in the osteoporosis or osteopenia group compared to healthy women (P < 0.0001). A negative correlation was observed between serum AGEs and lumbar spine bone density (BMD of lumbar spine, r = -0.249, P = 0.028; T-score of lumbar spine, r = -0.261, P = 0.021). Women with a increased level of serum AGEs (> 8.12 U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a 3.31-fold risk of osteopenia regarding the hip T-score. Conclusion: Serum AGEs could be used to monitor the severity and progression of osteoporosis. An increased serum level of AGEs was associated with impaired bone formation and was a risk factor for the development of osteoporosis. Targeting AGEs may represent a novel therapeutic approach for primary or secondary osteoporosis.

Background Unrecognized or untreated injury in patients with ankylosing spondylitis (AS) may develop anterior column spinal pseudoarthrosis with an open wedge bone defect. The methods of surgical treatment are controversial. Combined anterior and posterior stabilizations or posterior instrumentation with osteoclasis are beneficial as shown in an existing literature review. Case Report A 36-year-old Asian man with AS sustained a motor vehicle accident 2 years before presentation. At that time, his immediate magnetic resonance imaging scan demonstrated T10–T11bone edema and granulation tissue formation with fluid accumulation in T10–T11 disc space. He opted for conservative treatment. His back pain was then exacerbated 2 years after the accident, and he underwent three-dimensional (3D) computed tomography (CT) scan revealing a severe pseudoarthrosis with sclerotic margins across the T10 caudal end vertebra to the T11 upper end plate, with a maximal fracture gap of 15 mm. Spinal cord compression was not present. After selecting for an appropriate cage size with the aid of the preoperative 3D CT images, we used a single posterior approach to apply pedicle screws, removed pseudoarthrotic granulation tissue through an intertransverse posterior lateral approach without entering the spinal canal, and inserted a transforaminal lumbar interbody fusion (TLIF) cage with bone graft. There was radiographic evidence of spinal fusion at the 9-month follow-up, and the patient had resumed all normal daily activities. Conclusion The authors found that a less invasive single posterior surgical approach using a TLIF cage and pedicle screws could be applied to AS patients with combined thoracic pseudoarthrosis and an anterior column defect. Using a TLIF cage may provide circumferential stability immediately, bone graft fusion, and sagittal plane correction simultaneously. An appropriate cage size and placement selected with preoperative 3D CT images are the keys to success.

This study aimed to determine the safety and efficacy of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (Ultracet®) in patients with ankylosing spondylitis (AS). This was a 12-week, randomized, double-blind, placebo-controlled study. Sixty patients with active AS according to the Modified New York Criteria were enrolled. Active disease was defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for more than 3 at randomization. Subjects were randomized equally into two groups: the treatment group received aceclofenac plus Ultracet® one tablet twice a day, and the control group received aceclofenac plus placebo for 12 weeks. The primary endpoint was a difference of Assessment in Ankylosing Spondylitis (ASAS20) response criteria between two groups at week 12. At week 12, ASAS20 was achieved by 53.3 % of the aceclofenac plus Ultracet group and 31 % of the aceclofenac alone group (p = 0.047). For the pain visual analogue scale at week 12, there was a reduction of 45.6 % in aceclofenac plus Ultracet group and 25.7 % in the aceclofenac alone group (p = 0.087). There was no statistically significant difference between two groups in BASDAI, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Global Index, Physician Global Assessment, spinal mobility, ESR, hs-CRP, and Ankylosing Spondylitis Quality of Life Questionnaire. A slight increase in total adverse events was noted with dizziness (7.5 vs 1.5 %), vertigo (4.5 vs 1.5 %), and nausea/vomiting (6 vs 0 %) in the Ultracet arm compared to placebo. The tramadol 37.5 mg/acetaminophen 325 mg combination tablet (Ultracet®) might has additional effect to nonsteroidal anti-inflammatory drugs in the treatment of patients with ankylosing spondylitis. It showed marginal benefit in pain and disease activity. However, a slight increase in minor adverse events was noted.

Platelet-rich fibrin (PRF) by Choukroun's technique is produced in a totally natural manner, without using anticoagulant during blood harvest nor bovine thrombin and calcium chloride for platelet activation and fibrin polymerization. When delicately pressed between two gauzes, the PRF clot becomes a strong membrane with high potential in clinical application and tissue engineering. In this study, blood collection was carried out from healthy volunteers. Osteoblast cell line U2OS was used to evaluate the cell proliferation resulting from PRF by using colorimetric assay. Western blot was employed to evaluate the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK), receptor activator of nuclear factor-kappa B ligand (RANKL), and osteoprotegerin (OPG) in U2OS cells. PRF was found to increase osteoblast proliferation during 5 day incubation period (p0.05). PRF was found to increase ERK phosphorylation in U2OS cells (p0.05). OPG was significantly elevated by the stimulation with PRF (p0.05). However, there was no significant change in RANKL expression (p0.05). Taken together, PRF can stimulate osteoblasts proliferation. The activation of p-ERK and OPG expression by PRF suggests a potential role for new bone formation. The application of PRF may provide the benefit for the bone regeneration.

Osteopontin (OPN)-deficient mice are resistant to ovariectomy-induced osteoporosis. Therefore, we hypothesized that women with OPN overexpression may show less resistance to postmenopausal osteoporosis. In this study, we first demonstrated that serum OPN levels could be used as a biomarker for the early diagnosis of osteoporosis in postmenopausal women.Animal studies indicate that OPN-deficient mice are resistant to ovariectomy-induced osteoporosis.From 2004 to 2006, 124 women over the age of 45 were enrolled in a menopausal group, while another 95 women, from 25 to 45 years of age with regular menstruation, were enrolled into a childbearing age group. The serum concentrations of OPN were calculated using the enzyme-link immunosorbent assay method, and bone mineral densities were determined with dual energy X-ray absorptiometry.Serum OPN levels had a significant positive correlation with age (menopausal group, p0.0001) and a negative correlation with body weight, height, hip bone mineral density, and T-scores in the menopausal group. In contrast, there was a positive correlation with the E2 concentration and height, but there was no significant association with the above variables in the childbearing age group. Additionally, high serum OPN levels (14.7 ng/ml) was a significant risk factor causing menopausal osteoporosis (odds ratio = 2.96, 95% confidence interval, 1.055-8.345).Serum OPN levels could be used as a biomarker for the early diagnosis of osteoporosis in postmenopausal women.

Spinal abscess is rare in children, especially in young infants. The most common etiology is bacteria, Staphylococcus aureus in particular. Mycobacterium tuberculosis is another cause. We report an unusual cervical spinal abscess with spinal cord compression in a 13-month-old child. The presenting symptoms were weakness in the right arm and, predominantly, the right leg for 1 month. Magnetic resonance imaging showed an abscess of the cervical spine, extension with bony destruction, and spinal cord compression. The patient underwent an emergency neurosurgical decompression and laminectomy. Pathology and culture results confirmed Mycobacterium tuberculosis. After 12 months of antituberculosis treatment, the child could walk with a walker. At 37 months, he was able to walk without assistance. We conclude that spinal tuberculosis should be considered in cases of children with spinal cord-compression symptoms and an image showing an extraspinal abscess. Early diagnosis and prompt treatment are critical for maximizing a functional recovery.

Shikonin, a major ingredient in the Chinese traditional herb Lithospermum erythrorhixon, exhibits multiple biological functions including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we delineated the molecular mechanisms of shikonin in the apoptosis of 143B osteosarcoma cells. Shikonin reduced the cell viability of 143B cells in a dose- and time-dependent manner. The IC(50) at 24 h and 48 h for 143B cells was 4.55 and 2.01microM, respectively. A significantly elicited hypodiploid cell population was found in cells treated with 2, 4, and 8microM shikonin for 24 h. Moreover, treatment with shikonin induced reactive oxygen species (ROS) generation, increased extracellular signal-regulated kinase (ERK) phosphorylation, decreased B-cell lymphoma-2 (Bcl2) expression, and was accompanied by poly(ADP-ribose) polymerase (PARP) cleavage. Pretreatment with the antioxidant agent N-acetyl cysteine (NAC) not only reversed shikonin-induced ROS generation but also significantly attenuated the cytotoxic effects of shikonin in 143B cells. Furthermore, NAC attenuated shikonin-induced ERK phosphorylation. Taken together, our results reveal that shikonin increased ROS generation and ERK activation, and reduced Bcl2, which consequently caused the cells to undergo apoptosis. Therefore, shikonin may be a promising chemotherapeutic agent for osteosarcoma treatment.

Objectives: The purpose of this study was to examine the ex vivo effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the expression of urokinase-type plasminogen activator (u-PA), PA inhibitor-1 (PAI-1) and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] in the early knee osteoarthritis (OA) of humans. Design and methods: Samples of articular cartilage, meniscus and synovium of OA patients were obtained and cultured ex vivo in the presence or absence of NSAIDs (diclofenac sodium, nimesulide, celecoxib, valdecoxib, rofecoxib and etoricoxib). Results: Gelatin zymography showed that all NSAIDs generally decreased MMP-2 secretion in chondral, meniscal and synovial cultures as well as MMP-9 production in meniscal and synovial cultures. ELISA showed the inhibitions of u-PA secretion in chondral cultures by diclofenac and rofecoxib as well as in chondral and synovial cultures by nimesulide, celecoxib and etoricoxib at 48 h. On PAI-1 secretion, rofecoxib in synovial cultures and diclofenac, nimesulide, celecoxib and etoricoxib in chondral and synovial cultures had significantly suppressive effects at 48 h. Conclusions: This study clearly demonstrates that NSAIDs can down-regulate the PA/plasmin system and gelatinases expression during the early stage of knee OA, thereby possibly affect the structural progression of the disease. This inhibition seems to be independent selection of COX-1 and COX-2.

Background The up- and down-regulation of the osteoclastogenesis response depends on the estrogen/estrogen receptor (ER) signaling pathway. Previous reports have shown that the promoter hypermethylation and gene polymorphism of ERα are risks for menopausal osteoporosis. No previous study has evaluated the expression levels of ERα mRNA in menopausal osteoporosis using human subjects. We hypothesized that ERα mRNA expression may show less resistance to postmenopausal osteoporosis. Methods In this study, we enrolled 107 women older than 45 years without menstruation and classified them into control, osteopenia, and osteoporosis groups depending on their T-scores. The ERα mRNA levels in peripheral blood cells (PBCs) were analyzed via quantitative real-time reverse-transcription polymerase chain reaction (QRT-PCR), and estrogen in the serum was detected via ELISA. Results ERα mRNA levels in PBCs had a negative correlation with age and a positive correlation with estrogen and BAP in the osteopenia and osteoporosis groups, but not in the control group. Additionally, multivariate analysis showed that older age (> 55 years), and low ERα mRNA levels in PBLs (≦ 250.39 copies/μg DNA) were associated with an approximately 9.188-, and 31.25-fold risk of osteoporosis. Conclusion We conclude that ERα mRNA levels in PBLs could be used as an independent risk factor for postmenopausal osteoporosis. General significance Our findings suggested that ERα mRNA levels in PBLs may be more important than age and serum estrogen levels., Highlights • In this study, we found that 1. ERα mRNA levels in PBCs had a negative correlation with age and a positive correlation with estrogen and BAP in the osteopenia and osteoporosis groups; 2. No correlation between ERα mRNA levels in PBCs, estrogen and BAP in the control group; 3. age and ERα mRNA levels in PBLs could be used as independent risk factors for postmenopausal osteoporosis.

Introduction Transglutaminase 2 (TG2), a protein crosslinking enzyme with multiple biochemical functions, has been connected to various inflammatory processes. In this study, the involvement of TG2 in monosodium urate (MSU) crystal-induced inflammation was studied. Methods Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) were performed to detect TG2 expression in synovial fluid mononuclear cells (SFMCs) and synovial tissue from patients with gouty arthritis. MSU crystal-exposed RAW264.7 mouse macrophages were analyzed for interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), transforming growth factor β1 (TGF-β1) and TG2 expression by RT-PCR and enzyme-linked immunosorbent assay (ELISA). TG2 small interfering (si)-RNA-mediated silencing and overexpression in RAW264.7 cells were used to evaluate the involvement of TG2 in resolving MSU crystal-induced inflammation. The role of metastatic tumor antigen 1 (MTA1), a master chromatin modifier, was investigated by MTA1 si-RNA-mediated knockdown. In addition, the inflammatory responses were followed in wild type and TG2 null mice after being challenged with MSU crystals in an in vivo peritonitis model. Results TG2 expression was up-regulated in the synovium tissue and SFMCs from patients with gouty arthritis. The levels of MTA1, TG2, TGF-β1, IL-1β and TNF-α mRNAs were consistently increased in MSU crystal-stimulated RAW264.7 cells. si-MTA1 impaired the basal, as well as the MSU crystal-induced expression of TG2 and TGF-β1, but increased that of IL-1β and TNF-α. TG2 overexpression dramatically suppressed MSU crystal-induced IL-1β and TNF-α, but significantly enhanced the TGF-β1 production. Neutralizing TGF-β antibodies or inhibition of the crosslinking activity of TG2 attenuated these effects. On the contrary, loss of TG2 resulted in a reduced TGF-β, but in an increased IL-1β and TNF-α production in MSU crystal-stimulated RAW264.7 cells and mouse embryonic fibroblasts (MEFs). MSU crystal-stimulated IL-1β production was Janus kinase 2 (JAK2)-signaling dependent and TG2-induced TGF-β suppressed the activity of it. Finally, TG2-deficient mice exhibited hyper inflammatory responses after being challenged with MSU crystals in an in vivo peritonitis model. Conclusions These findings reveal an inherent regulatory role of the MTA1-TG2 pathway in the self-limitation of MSU crystal-induced inflammation via positively regulating the levels of active TGF-β1 in macrophages that opposes the MSU crystal-induced JAK2-dependent pro-inflammatory cytokine formation. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0592-7) contains supplementary material, which is available to authorized users.

Most spinal arachnoid cysts are asymptomatic and detected incidentally during magnetic resonance imaging or myelography. The etiology of intraspinal arachnoid cyst is not yet clear. We present two children with three spinal extradural arachnoid cysts and each cyst protruded from a separate dura defect. In both patients, plain radiographs demonstrated widening of the interpedicular distance, which suggested progressive widening of the spinal bony canal. Limited laminectomy was performed to remove the intraspinal cysts. Separate dura defects, the apparent predisposing factors, were also found and repaired. The patients completely recovered neurologically. Radical cyst removal and dura defect closure are the surgical intervention of choice in patients with symptomatic extradural arachnoid cyst.

To report an unusual presentation of a thoracic neurenteric cyst.To increase knowledge about the pathogenesis and treatment of intraspinal neurenteric cyst.Intraspinal neurenteric cysts (enterogenous cysts) are very rare congenital cysts of endodermal origin. The diagnosis usually is established during the first or second decade of life. Those cysts are frequently associated with vertebral or spinal cord anomalies and dual malformation with mediastinal or abdominal cysts.A 50-year-old man presented with 1 year of left midthoracic intercostal pain after chest compression injury. Several months before admission, he felt left lower extremity weakness with right-side numbness. Plain radiography of thoracic spine was normal while MRI showed a cystic mass at T7, T8 level ventral to the spinal cord with cord compression. The spinal cord was displaced to the posterior more to the right side, mimicking hemisection of the left side of the spinal cord.Thoracic laminectomy was performed and the intraspinal cyst was removed. The pathology report indicated neuroenteric cyst. The postoperative course was uneventful and the signs of myelopathy improved immediately. The patient appeared well after 2 years of follow-up.Intraspinal neuroenteric cyst without plain vertebral anomaly may occur after trauma in middle aged adult life with Brown-Sequard syndrome. Successful treatment requires early recognition of those cysts and their associated abnormalities.

OBJECTIVES This study aimed to identify potential blood-derived biomarkers distinguishing patients with ankylosing spondylitis from those with mechanical low back pain. METHODS Serum and synovial fluid samples from our cohorts were assayed by using enzyme-linked immunosorbent assay for the following inflammatory biomarkers: interleukin (IL)-1α, IL-6, IL-8, IL-17, IL-23, monocyte chemotactic protein (MCP)-1, macrophage inflammatory proteins (MIP)-1α, MIP-1β, tumor necrosis factor-α (TNF-α), interferon-α (IFN-α), IFN-β, metalloproteinase (MMP-3), and bone morphogenetic protein 7 (BMP-7). RESULTS After screening, a panel of serum and synovial fluid samples with a series of potential biomarkers, cytokines including IL-6, IL-8, MMP-3, and MCP-1 were selected for additional testing because they exhibited higher concentrations than paired serum samples in the synovial fluid. Sera obtained from 50 patients with ankylosing spondylitis and 27 patients with mechanical low back pain were measured for these biomarkers. CONCLUSIONS The MCP-1 serum was identified as a biomarker candidate, distinguishing ankylosing spondylitis from mechanical low back pain with a sensitivity of 96% and a specificity of 83.3%.

In this pilot study, we demonstrated that women with osteopontin (OPN) over-expression show less resistance to postmenopausal osteoporosis than women with normal OPN levels. We hypothesized that the levels of plasma OPN could be used as a treatment indicator for intermittent parathyroid hormone (PTH)-treated menopausal osteoporosis. We demonstrated that plasma OPN levels could be used as a biomarker for early treatment response. Animal studies indicate that OPN-deficient mice are resistant to ovariectomy induced osteoporosis. Our pilot study also demonstrated women with OPN over expression may show less resistance to postmenopausal osteoporosis. The role of plasma OPN in PTH1-34-treated osteoporosis remains unclear. From September 2005 to September 2006, 31 menopausal women over 45 years of age with severe osteoporosis were enrolled in our study. Subjects were treated with PTH1-34 subcutaneously at a dose of 20 μg/day. Plasma OPN levels and BMD of the lumbar spine and hip were measured using ELISA and dual-energy X-ray absorptiometry at baseline, 3, 6, and 9 months. Response to the treatment was assessed by the sequential change in bone mineral density and OPN expression using a general linear mixed model. The plasma OPN decreased sequentially and significantly throughout the 9-month treatment course from 20.75 ± 5.36 to 11.2 ± 4.37 ng/ml (p

UNLABELLED A controversy between pharmacologic and surgical treatment of intraspinal gout exists in the literature. If gout is diagnosed timely, pharmacologic therapy may avert the need of surgery. The lack of readily available synovial fluid makes the diagnosis particularly difficult. The purpose of this study was to evaluate the clinical pictures and magnetic resonance imaging features in rapid differentiations of intraspinal gout. I retrospectively evaluated lumbar intraspinal tophaceous gout without the classic radiographic punched-out lesions. Four patients (average age, 65 years) had a history of hyperuricemia with multiple tophaceous deposits in the joints or visceral organs or both. The common presentations were low back pain with or without inflammatory reaction (fever, elevated C-reactive protein level, and mild leukocytosis). The patients also presented with intermittent claudication or radiculopathy of variable duration or both. The gouty tophi yielded homogeneous and hypointense masses on T1- and T2-weighted images, with multiple hypointense speckles. The masses were located in bilateral lumbar facet joints in all patients, with additional midline extension along the ligamentum flavum in three. All patients had uneventful outcomes after surgical decompression and pharmacologic treatment. Rapid deposition of tophi may aggravate nerve compression. If neurologic deficits are found, surgical decompression can provide a satisfactory outcome. LEVEL OF EVIDENCE Therapeutic study, Level IV. See the Guidelines for Authors for a complete description of levels of evidence.

The optimal treatment of salmonella spondylodiscitis is controversial. The cases of eight patients who had salmonella spondylitis without sickle cell disease were reviewed. Back pain (100%), fever (75%), and elevated C-reactive protein levels (100%) were common, but gastrointestinal symptoms were not (0%). Six patients had positive blood cultures, and the other two had positive tissue cultures. Group C1 salmonella was the most common serotype. Two patients with coexisting aortic mycotic aneurysms had immediate aneurysm resection. Three others responded favorably to appropriate antibiotics, and three required subsequent surgical reconstruction because of neurologic impairment or osseous instability. Clinical outcomes were significantly better than those of 46 previously reported patients. Salmonella spondylodiscitis usually responds favorably to appropriate antibiotics; consequently, a tissue diagnosis is important. Operative interventions are necessary only for patients with coexisting aneurysms or ongoing osseous instability. A ruptured aortic aneurysm with pseudoaneurysm may mimic a paravertebral abscess, and surgery at the site of an unsuspected aneurysm may precipitate life-threatening hemorrhage. Satisfactory results may be depend on early surgical intervention for a mycotic aneurysm and also are related to host immunity.

Symptomatic congenital intraspinal cysts are uncommon but not rare. Since these cysts may have various manifestations, a careful differential diagnosis is needed. We retrospectively reviewed findings in 3 women and 2 men (age range, 10–50 years) with 6 symptomatic cysts of the thoracic or thoracolumbar spine. In addition, we statistically analyzed the patients’ Nurick myelopathy grades before and after treatment. Pain and spastic paraparesis were the most frequent manifestations. Radiographs showed the widening of the spinal bony canal in 3 patients with extradural arachnoid cysts. All patients received limited laminectomy and appropriate surgical procedures. Pathology reports indicated neurenteric (n = 1), arachnoid (n = 4), and epidermoid (n = 1) cysts. Their functional status significantly improved by a mean of 2.6 Nurick points (p = 0.0002). Our findings confirm that these cysts have various manifestations. Congenital intraspinal cyst should be included in the differential diagnosis for patients with back pain, radiculopathy, cauda equina syndrome, Brown-Sequard syndrome, or myelopathy. The advent of MR imaging and increased knowledge about the pathogenesis of these cysts have improved the ease and accuracy of their early diagnosis; in addition, postoperative prognoses are excellent if surgery is performed early.

Most spinal arachnoid cysts are asymptomatic and detected incidentally during magnetic resonance imaging or myelography. The etiology of intraspinal arachnoid cyst is not yet clear. We present two children with three spinal extradural arachnoid cysts and each cyst protruded from a separate dura defect. In both patients, plain radiographs demonstrated widening of the interpedicular distance, which suggested progressive widening of the spinal bony canal. Limited laminectomy was performed to remove the intraspinal cysts. Separate dura defects, the apparent predisposing factors, were also found and repaired. The patients completely recovered neurologically. Radical cyst removal and dura defect closure are the surgical intervention of choice in patients with symptomatic extradural arachnoid cyst.

This paper presents progress of collinear beam (CB) AOTFs as wavelength routing switches (WRS) in DWDM networks. Significant improvement in the CBAOTF bandpass response was achieved. The measured performance at 1550nm shows a FWHM of 0.5nm and a sidelobe bandpass below 22dB at a wavelength spacing of 0.8nm from the center wavelength. By using two cascaded dual polarization AOTFs, a 2 X 2 WRS can be constructed that yields an extinction ratio greater than 35dB.

This paper proposes a new ADPCM method for image coding called directional ADPCM which can remove more redundancy from the image signals than the conventional ADPCM. The conventional ADPCM calculates the two-dimensional prediction coefficients by using the correlation functions followed by solving the Yule-Walker equation. Actually, the quantities of correlation functions to be the approximation of the correlation function. However, the block size is limited by the error accumulation effect during packet transmission. Using small block may induce the unregulated prediction coefficients. Therefore, we need to develop the directional ADPCM system to overcome such a problem and to have better prediction result. Our directional ADPCM utilized the fan- shape filters to obtain the energy distribution in four directions and then determines the four directional prediction coefficient. All the fan-shape filters are designed by using the singular value decomposition (SVD) method, the two-dimensional Hilbert transform technique, and the frequency weighting concept. In the experiments, we illustrate that the M.S.E. for the directional ADPCM is less than that of the conventional ADPCM.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

This paper proposes a new ADPCM method for image coding called directional ADPCM which canremove more redundancy from the image signals than the conventional ADPCM. The conventional ADPCMcalculates the two-dimensional prediction coefficients by using the correlation functions and solving the Yule-Walker equation. Actually, the quantities of correlation functions are replaced by the sample averages.Therefore, this solution will not be optimum. Our directional ADPCM utilizes the directional filters to obtain the energy distribution in four directions and then determines the four directional prediction coefficients. All the directional filters are designed by using the singular value decomposition (SVD) method and the two-dimensional Hilbert transform technique. In the experiments, we illustrate that the M.S.E for the directional ADPCM is less than that of the conventional ADPCM.Keywords : Directional ADPCM, Sigular value decomposition, Directional filters. 1. INTRODUCTION Recently, the image and video compression tecimologies have drawn a lot of attentions. Many image

Preliminary results of a study aimed at the development of a simultaneous signal instantaneous frequency measurement (IFM) receiver using optical implementation methods are reported. A method for detecting simultaneous signals in an IFM receiver is briefly reviewed. Two architectures (coherent and incoherent) for optical phase correlators are then described and compared. Some considerations concerning the practical implementation of the two architectures are discussed.

This paper reviews the operating principle of the acousto-optic tunable filter (AOTF) and describes some of the recent progress. A ray tracing algorithm was derived that was used to determine the image aberration due to the AOTF. The calculated result is compared with the experimental result of the AOTF configured as an electronically tuned imaging spectrometer. Due to the recent progress of AOTF technology, a wideband (10 nm) visible AOTF with a one inch aperture is now realizable.

This paper describes the application of acousto-'optic (AO) spectrum analysis techniques for astronomicalspectrometers. The design of a 2 GHz bandwidth AO spectrometer and the performance limitations of the technology are discussed. Two alternative architecture areproposed. The new approaches appear promising for increasing the instantaneous bandwidth to greater than 5 GHz. 1. Introduction The large instantaneous bandwidth, fine frequency resolution and low power potential of the acousto—optic (AO) channelized receiver make it well-suited for wideband spectrum analysis of RF signals. Most of the AO channelized receiver technology developed in the past years have been directed to electronic warfare (EW) applications [1].In recent years, there has been considerable interest in exploiting the AO technology to the development of wideband RF spectrometers for millimeter radio astronomyapplications. Conventional spectrometers based on filterbanks are complex, bulky and expensive to construct.

RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and cell migration in a cultured cardiomyoblast cell line, H9c2. We demonstrated that RhoGDIβ plays a previously undefined role in regulating Rac1 expression through transcription to induce hypertrophic growth and cell migration and that these functions are blocked by the expression of a dominant-negative form of Rac1. We also demonstrated that knockdown of RhoGDIβ expression by RNA interference blocked RhoGDIβ-induced Rac1 expression and cell migration. We demonstrated that the co-expression of ZAK and RhoGDIβ in cells resulted in an inhibition in the activity of ZAK to induce ANF expression. Knockdown of ZAK expression in ZAK-RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the activities of RhoGDIβ.