Combination of transverse myelitis and arachnoiditis in cauda equina syndrome of long-standing ankylosing spondylitis: MRI features and its role in clinical management

The cauda equina syndrome (CES) is a rare neurological complication of ankylosing spondylitis (AS). Imaging diagnosis of CES in long-standing AS patients (CES-AS) using myelography, computed tomography (CT), and magnetic resonance imaging (MRI) were reported in the literature. They, however, demonstrate only the chronic abnormalities of CES-AS, i.e., dural ectasia, dorsal dural diverticula, and selective bone erosion at the posterior elements of the vertebrae. To our knowledge, imaging features of acute intradural inflammation in CES-AS were not described. We report a patient of CES-AS in whom MRI disclosed acute transverse myelitis and arachnoiditis along the lower spinal cord, and discuss the pathogenesis of CES-AS and the role of MRI in clinical management

Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy

Introduction: The objective of this study was to investigate the effects of tumor necrosis factor (TNF)-alpha inhibitors on circulating T helper-type 17 (Th17) cells and Th17-related cytokines in patients with rheumatoid arthritis (RA). Methods: The frequencies of circulating Th17 cells and serum levels of Th17-related cytokines were determined using flow cytometry analysis and ELISA, respectively, in 48 RA patients both before (baseline) and six months after anti-TNF-alpha therapy. Therapeutic response was evaluated using European League Against Rheumatism (EULAR) response criteria. Results: Significantly higher baseline frequencies of circulating Th17 cells and serum levels of interleukin (IL)-6, IL17, IL-21, IL-23 and TNF-alpha were observed in active RA patients than in 12 healthy controls (all P < 0.001). After anti-TNF-alpha therapy, 36 patients (75%) were EULAR responders (20 good responders and 16 moderate responders) and 12 (25.0%) were non-responders. The mean levels of circulating Th17 cells and IL-17 significantly decreased (1.13% vs. 0.79%; 43.1 pg/ml vs. 27.8 pg/ml; respectively, both P < 0.001) in parallel with clinical remission in responders. Levels of IL-6, IL-21, IL-23 and TNF-alpha were significantly decreased after anti-TNF-alpha therapy in responders. In contrast, the mean levels of circulating Th17 cells and IL-17 significantly increased after anti-TNF-alpha therapy (2.94% vs. 4.23%; 92.1 pg/ml vs. 148.6 pg/ml; respectively, both P < 0.05) in non-responders. Logistic regression analysis identified a high baseline level of IL-17 as a significant predictor of poor therapeutic response. Conclusions: The beneficial effect of anti-TNF-alpha therapy might involve a decrease in Th17-related cytokines in responders, whereas rising levels of circulating Th17-cells and IL-17 were observed in patients with an inadequate response to anti-TNF-alpha therapy

Properties of a Dilute Bose Gas near a Feshbach Resonance

In this paper, properties of a homogeneous Bose gas with a Feshbach resonance are studied in the dilute region at zero temperature. The stationary state contains condensations of atoms and molecules. The ratio of the molecule density to the atom density is $\pi na^3$. There are two types of excitations, molecular excitations and atomic excitations. Atomic excitations are gapless, consistent with the traditional theory of a dilute Bose gas. The molecular excitation energy is finite in the long wavelength limit as observed in recent experiments on $^{85}$Rb. In addition, the decay process of the condensate is studied. The coefficient of the three-body recombination rate is about 140 times larger than that of a Bose gas without a Feshbach resonance, in reasonably good agreement with the experiment on $^{23}$Na.Comment: 11 pages, 1 figure, comparison between the calculated three-body recombination rate and the experimental data for Na system has been adde

Spiral phase and phase separation of the double exchange model in the large-S limit

The phase diagram of the double exchange model is studied in the large-S limit at zero temperature in two and three dimensions. We find that the spiral state has lower energy than the canted antiferromagnetic state in the region between the antiferromagnetic phase and the ferromagnetic phase. At small doping, the spiral phase is unstable against phase separation due to its negative compressibility. When the Hund coupling is small, the system separates into spiral regions and antiferromagnetic regions. When the Hund coupling is large, the spiral phase disappears completely and the system separates into ferromagnetic regions and antiferromagnetic regions.Comment: 7 pages, 3 postscript figures. To be published in Phys. Rev.

Targeting the Stress-Induced Protein NUPR1 to Treat Pancreatic Adenocarcinoma

Cancer cells activate stress-response mechanisms to adapt themselves to a variety of stressful conditions. Among these protective mechanisms, those controlled by the stress-induced nuclear protein 1 (NUPR1 ) belong to the most conserved ones. NUPR1 is an 82-residue-long, monomeric, basic and intrinsically disordered protein (IDP), which was found to be invariably overexpressed in some, if not all, cancer tissues. Remarkably, we and others have previously showed that genetic inactivation of the Nupr1 gene antagonizes the growth of pancreatic cancer as well as several other tumors. With the use of a multidisciplinary strategy by combining biophysical, biochemical, bioinformatic, and biological approaches, a trifluoperazine-derived compound, named ZZW-115, has been identified as an inhibitor of the NUPR1 functions. The anticancer activity of the ZZW-115 was first validated on a large panel of cancer cells. Furthermore, ZZW-115 produced a dose-dependent tumor regression of the tumor size in xenografted mice. Mechanistically, we have demonstrated that NUPR1 binds to several importins. Because ZZW-115 binds NUPR1 through the region around the amino acid Thr68, which is located into the nuclear location signal (NLS) region of the protein, we demonstrated that treatment with ZZW-115 inhibits completely the translocation of NUPR1 from the cytoplasm to the nucleus by competing with importins

ZZW-115-dependent inhibition of NUPR1 nuclear translocation sensitizes cancer cells to genotoxic agents

Establishing the interactome of the cancer-associated stress protein Nuclear Protein 1 (NUPR1), we found that it binds to several hundreds of proteins, including proteins involved in nuclear translocation, DNA repair, and key factors of the SUMO pathway. We demonstrated that the NUPR1 inhibitor ZZW-115, an organic synthetic molecule, competes with importins for the binding to the NLS region of NUPR1, thereby inhibiting its nuclear translocation. We hypothesized, and then proved, that inhibition of NUPR1 by ZZW-115 sensitizes cancer cells to DNA damage induced by several genotoxic agents. Strikingly, we found that treatment with ZZW-115 reduced SUMOylation of several proteins involved in DNA damage response (DDR). We further report that the presence of recombinant NUPR1 improved the SUMOylation in a cell-free system, indicating that NUPR1 directly stimulates the SUMOylation machinery. We propose that ZZW-115 sensitizes cancer cells to genotoxic agents by inhibiting the nuclear translocation of NUPR1 and thereby decreasing the SUMOylation-dependent functions of key proteins involved in the DDR

JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma

Chromosome 17q21-ter is commonly gained in neuroblastoma, but it is unclear which gene in the region is important for tumorigenesis. The JMJD6 gene at 17q21-ter activates gene transcription. Here we show that JMJD6 forms protein complexes with N-Myc and BRD4, and is important for E2F2, N-Myc and c-Myc transcription. Knocking down JMJD6 reduces neuroblastoma cell proliferation and survival in vitro and tumor progression in mice, and high levels of JMJD6 expression in human neuroblastoma tissues independently predict poor patient prognosis. In addition, JMJD6 gene is associated with transcriptional super-enhancers. Combination therapy with the CDK7/super-enhancer inhibitor THZ1 and the histone deacetylase inhibitor panobinostat synergistically reduces JMJD6, E2F2, N-Myc, c-Myc expression, induces apoptosis in vitro and leads to neuroblastoma tumor regression in mice, which are significantly reversed by forced JMJD6 over-expression. Our findings therefore identify JMJD6 as a neuroblastoma tumorigenesis factor, and the combination therapy as a treatment strategy