bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of NCAM and OCIAD1 in well-differentiated thyroid carcinoma: correlation with the risk of distant metastasis
Authors: Yang An-Hang , Chen Jui-Yu , Lee Chen-Hsen , Chen Jun-Yi 
Published: November 2011

AimsThe biomarkers representing the metastatic potential of well-differentiated thyroid carcinoma remain to be established. A study was undertaken to find whether the expression status of neural cell adhesion molecule (NCAM) and/or ovarian cancer immunoreactive antigen domain containing 1 (OCIAD1) is associated with the metastatic potential of differentiated thyroid carcinoma.MethodsNCAM and OCIAD1 were analysed by immunohistochemistry on tissue microarrays.ResultsAmong 214 well-differentiated thyroid carcinomas, 68 patients had distant metastases. Immunohistochemical analyses showed that the majority of benign thyroid lesions expressed NCAM while a significant proportion of thyroid carcinomas lost or had reduced NCAM expression. Both follicular and papillary carcinomas with distant metastasis had a significantly higher frequency of preserving NCAM expression. Hierarchical clustering analysis showed that OCIAD1 had significant differential expression between benign and malignant thyroid lesions. The overall metastatic-to-localised tumour ratio was higher in NCAM-expressing clusters, but the difference between ratios of OCIAD1-positive and OCIAD1-negative subclusters was not significant.ConclusionsThese analyses suggest that the preservation of NCAM expression in well-differentiated thyroid carcinoma is an indicator for a higher risk of distant metastasis. OCIAD1 is a potential biomarker of thyroid carcinoma but had no significant additive effect on the risk of distant metastasis. Further elucidation of the molecular mechanisms underlying the NCAM-mediated cellular processes will be beneficial for the development of effective treatments against the metastasis of thyroid carcinoma.
ERK1/2 Regulation of CD44 Modulates Oral Cancer Aggressiveness
Authors: Judd Nancy P. , Winkler Ashley E. , Murillo-Sauca Oihana , Brotman Joshua J. , Law Jonathan H. , Lewis James S. , Dunn Gavin P. , Bui Jack D. , Sunwoo John B. , Uppaluri Ravindra 
Published: November 2011

AbstractCarcinogen-induced oral cavity squamous cell carcinoma (OSCC) incurs significant morbidity and mortality and constitutes a global health challenge. To gain further insight into this disease, we generated cell line models from 7,12-dimethylbenz(a)anthracene–induced murine primary OSCC capable of tumor formation upon transplantation into immunocompetent wild-type mice. Whereas several cell lines grew rapidly and were capable of metastasis, some grew slowly and did not metastasize. Aggressively growing cell lines displayed ERK1/2 activation, which stimulated expression of CD44, a marker associated with epithelial to mesenchymal transition and putative cancer stem cells. MEK (MAP/ERK kinase) inhibition upstream of ERK1/2 decreased CD44 expression and promoter activity and reduced cell migration and invasion. Conversely, MEK1 activation enhanced CD44 expression and promoter activity, whereas CD44 attenuation reduced in vitro migration and in vivo tumor formation. Extending these findings to freshly resected human OSCC, we confirmed a strict relationship between ERK1/2 phosphorylation and CD44 expression. In summary, our findings identify CD44 as a critical target of ERK1/2 in promoting tumor aggressiveness and offer a preclinical proof–of-concept to target this pathway as a strategy to treat head and neck cancer. Cancer Res; 72(1); 365–74. ©2011 AACR.
Safety and Efficacy of Allogeneic Cell Therapy in Infarcted Rats Transplanted With Mismatched Cardiosphere-Derived Cells
Authors: Malliaras Konstantinos , Li Tao-Sheng , Luthringer Daniel , Terrovitis John , Cheng Ke , Chakravarty Tarun , Galang Giselle , Zhang Yiqiang , Schoenhoff Florian , Van Eyk Jennifer , Marbán Linda , Marbán Eduardo 
Published: November 2011

Background—
Cardiosphere-derived cells (CDCs) are an attractive cell type for tissue regeneration, and autologous CDCs are being tested clinically. However, autologous therapy necessitates patient-specific tissue harvesting and cell processing, with delays to therapy and possible variations in cell potency. The use of allogeneic CDCs, if safe and effective, would obviate such limitations. We compared syngeneic and allogeneic CDC transplantation in rats from immunologically-mismatched inbred strains.

Methods and Results—

In vitro, CDCs expressed major histocompatibility complex class I but not class II antigens or B7 costimulatory molecules. In mixed-lymphocyte cocultures, allogeneic CDCs elicited negligible lymphocyte proliferation and inflammatory cytokine secretion. In vivo, syngeneic and allogeneic CDCs survived at similar levels in the infarcted rat heart 1 week after delivery, but few syngeneic (and even fewer allogeneic) CDCs remained at 3 weeks. Allogeneic CDCs induced a transient, mild, local immune reaction in the heart, without histologically evident rejection or systemic immunogenicity. Improvements in cardiac structure and function, sustained for 6 months, were comparable with syngeneic and allogeneic CDCs. Allogeneic CDCs stimulated endogenous regenerative mechanisms (cardiomyocyte cycling, recruitment of c-kit
+
cells, angiogenesis) and increased myocardial vascular endothelial growth factor, insulin-like growth factor-1, and hepatocyte growth factor equally with syngeneic CDCs.

Conclusions—
Allogeneic CDC transplantation without immunosuppression is safe, promotes cardiac regeneration, and improves heart function in a rat myocardial infarction model, mainly through stimulation of endogenous repair mechanisms. The indirect mechanism of action rationalizes the persistence of benefit despite the evanescence of transplanted cell survival. This work motivates the testing of allogeneic human CDCs as a potential off-the-shelf product for cellular cardiomyoplasty.
Small Irregular Ice Crystals in Tropical Cirrus
Authors: Nousiainen Timo , Lindqvist Hannakaisa , McFarquhar Greg M. , Um Junshik 
Published: November 2011

Abstract
Images acquired by a Cloud Particle Imager (CPI) are analyzed to compile a statistical covariance function of radius for an ensemble of small, irregular, quasi-spherical ice crystals in tropical cirrus measured during the Department of Energy Atmospheric Radiation Measurement Program’s Tropical Warm Pool International Cloud Experiment. The infrequent occurrence of multiple particles in single CPI frames suggests that most crystals sampled were natural ice crystals rather than artifacts from large particles shattering on probe tips. The covariance function is used in conjunction with the Gaussian random sphere geometry to generate three-dimensional model ice particles for ray-optics simulations at 550-nm wavelength. The crystal shapes and single-scattering properties are compared with those obtained by the same methodology for midlatitude cirrus sampled over Oklahoma. The small tropical ice crystals are closer to spherical than their midlatitude counterparts and, consequently, their asymmetry parameters are larger, but the differences are not significant from the standpoint of climate studies. Because some quasi-spherical ice crystals seem partially faceted, a convex hull transformation is introduced that increases the asymmetry parameter from 0.785 to 0.808. Further modifying the covariance function to promote sixfold symmetry in the model crystals increases the asymmetry parameter to 0.818. The introduction of internal scatterers, such as air bubbles, has a larger impact, decreasing the asymmetry parameter by up to tens of percent, depending on their amount and characteristics. Unfortunately, no data are available to determine realistic values for the internal scatterers to assess their likely actual impact.
Role for Ion Transport in Porcine Vocal Fold Epithelial Defense to Acid Challenge
Authors: Erickson‐Levendoski Elizabeth , Sivasankar M. Preeti 
Published: November 2011

ObjectiveThe vocal fold epithelium is routinely exposed to gastric contents, including acid and pepsin, during laryngopharyngeal reflux events. The epithelium may possess intrinsic defenses to reflux. The first objective of the current study was to examine whether vocal fold epithelial ion transport is one potential mechanism of defense to gastric contents. The second objective was to determine whether ion transport in response to gastric contents is associated with the secretion of bicarbonate.Study DesignProspective design in excised porcine larynges.SettingLaboratory.Subjects and MethodsPorcine vocal folds (N = 56) were exposed on the luminal surface to acid, pepsin, or sham challenges. Ion transport at baseline and following challenge exposure was measured using electrophysiological techniques. To examine specific ion transport mechanisms, vocal folds were pretreated with either a sodium channel blocker or bicarbonate channel blocker.ResultsWithin 60 seconds of acid but not pepsin exposure, there was a significant increase in ion transport. This rapid increase in ion transport was transient and related to bicarbonate secretion.ConclusionThe current data suggest that porcine vocal folds immediately increase bicarbonate secretion following exposure to acid. Bicarbonate secretion may act to neutralize acid. These findings contribute to the identification of the mechanisms underlying vocal fold defense to reflux and offer implications for the development of treatments for reflux‐induced vocal fold injury.
Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy
Authors: Chiarini M , Serana F , Zanotti C , Capra R , Rasia S , Rottoli M , Rovaris M , Caputo D , Cavaletti G , Frigo M , Frigeni B , Clerici R , Rezzonico M , Caimi L , Imberti L 
Published: November 2011

Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy. Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population. Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the ‘central memory-like’ Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy. Conclusions: The selective increase of ‘central memory-like’ subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.
Simvastatin protects auditory hair cells from gentamicin-induced toxicity and activates Akt signaling in vitro
Authors: Brand Yves , Setz Cristian , Levano Soledad , Listyo Alwin , Chavez Eduardo , Pak Kwang , Sung Michael , Radojevic Vesna , Ryan Allen F , Bodmer Daniel 
Published: November 2011

Abstract

Background
Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, known as statins, are commonly used as cholesterol-lowering drugs. During the past decade, evidence has emerged that statins also have neuroprotective effects. Research in the retina has shown that simvastatin, a commonly used statin, increases Akt phosphorylation in vivo, indicating that the PI3K/Akt pathway contributes to the protective effects achieved. While research about neuroprotective effects have been conducted in several systems, the effects of statins on the inner ear are largely unknown.

Results
We evaluated whether the 3-hydroxy-3-methylglutaryl-coenzyme A reductase is present within the rat cochlea and whether simvastatin is able to protect auditory hair cells from gentamicin-induced apoptotic cell death in a in vitro mouse model. Furthermore, we evaluated whether simvastatin increases Akt phosphorylation in the organ of Corti. We detected 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in organ of Corti, spiral ganglion, and stria vascularis by reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, we observed a dose-dependent and significant reduction of hair cell loss in organs of Corti treated with simvastatin in addition to gentamicin, as compared to samples treated with gentamicin alone. The protective effect of simvastatin was reversed by addition of mevalonate, a downstream metabolite blocked by simvastatin, demonstrating the specificity of protection. Finally, Western blotting showed an increase in organ of Corti Akt phosphorylation after simvastatin treatment in vitro.

Conclusion
These results suggest a neuroprotective effect of statins in the inner ear, mediated by reduced 3-hydroxy-3-methylglutaryl-coenzyme A reductase metabolism and Akt activation.
Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex
Authors: Onozawa Kitaro , Yagasaki Yuki , Izawa Yumi , Abe Hiroyuki , Kawakami Yoriko 
Published: November 2011

Abstract

Background
We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC). The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA) to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS) delivered to the BLA on nociceptive responses in the rat PFC.

Results
HFS induced long lasting suppression (LLS) of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA) receptor antagonists (2-amino-5-phosphonovaleric acid (APV), dizocilpine (MK-801)) and also metabotropic glutamate receptor (mGluR) group antagonists (α-methyl-4-carboxyphenylglycine (MCPG), and 2-[(1S,2S)-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl)-D-alanine (LY341495)), prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA) on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA) injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride) and D4 (3-{[4-(4-chlorophenyl) piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870)), microinjected into the PFC, inhibited LLS of nociceptive responses.

Conclusions
Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.
Neuromelanin is an immune stimulator for dendritic cells in vitro
Authors: Oberländer Uwe , Pletinckx Katrien , Döhler Anja , Müller Nora , Lutz Manfred B , Arzberger Thomas , Riederer Peter , Gerlach Manfred , Koutsilieri Eleni , Scheller Carsten 
Published: November 2011

AbstractBackgroundParkinson's disease (PD) is characterized at the cellular level by a destruction of neuromelanin (NM)-containing dopaminergic cells and a profound reduction in striatal dopamine. It has been shown recently that anti-melanin antibodies are increased in sera of Parkinson patients, suggesting that NM may act as an autoantigen. In this study we tested whether NM is being recognized by dendritic cells (DCs), the major cell type for inducing T- and B-cell responsesin vivo. This recognition of NM by DCs is a prerequisite to trigger an adaptive autoimmune response directed against NM-associated structures.ResultsMurine DCs were treated with NM of substantia nigra (SN) from human subjects or with synthetic dopamine melanin (DAM). DCs effectively phagocytized NM and subsequently developed a mature phenotype (CD86high/MHCIIhigh). NM-activated DCs secreted the proinflammatory cytokines IL-6 and TNF-α. In addition, they potently triggered T cell proliferation in a mixed lymphocyte reaction, showing that DC activation was functional to induce a primary T cell response. In contrast, DAM, which lacks the protein and lipid components of NM but mimics the dopamine-melanin backbone of NM, had only very little effect on DC phenotype and function.ConclusionsNM is recognized by DCsin vitroand triggers their maturation. If operativein vivo, this would allow the DC-mediated transport and presentation of SN antigens to the adaptive immune system, leading to autoimmmunity in susceptible individuals. Our data provide a rationale for an autoimmune-based pathomechanism of PD with NM as the initial trigger.
Paraneoplastic syndrome mimicking adult-onset Still's disease caused by advanced lung cancer: a case report
Authors: Wu Ning , Li Qiang , Gu Chang-Xin , Ahmed Toqeer , Yao Xiao-Peng 
Published: November 2011

Abstract

Background
Paraneoplastic syndromes (PNSs) are common complications of lung cancer and often develop preceding the diagnosis of primary malignancy. Rheumatologic PNSs mimicking Adult-Onset Still' s Disease (AOSD) is a rare condition with only a limited number of cases reported in the literature, none of which was associated with lung cancer. It is often difficult to differentiate AOSD-like paraneoplasia from coincidental AOSD based on the clinical manifestations.

Case presentation
Here we present a 56-year-old man with advanced lung adenocarcinoma who developed a remittent fever together with pharyngodynia and joint pain after first cycle of chemotherapy with paclitaxel plus carboplatin. Although a leukocytosis was detected, no evidence of infection was acquired and empirical antibiotic treatment was ineffective. A temple skin rash, abnormal hepatic function and a remarkable elevated level of serum ferritin occurred later in this patient, which highly supported a potential diagnosis of AOSD. The patient was finally diagnosed as AOSD-like PNS considering the good and prompt response to a short-term administration of non-steroidal anti-inflammatory drug and subsequent cycles of effective chemotherapy with pemetrexed plus cisplatin.

Discussion and conclusions
Though rare, AOSD-like PNS can be one of the potential diagnoses in lung cancer patients with fever of undetermined origin, especially those having no response to antibiotic treatment. Management consists of control of the underlying malignancy and symptomatic treatment of the syndromes with non-steroidal anti-inflammatory drugs or corticosteroids.
Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model
Authors: Mokbel Abir N , El Tookhy Omar S , Shamaa Ashraf A , Rashed Laila A , Sabry Dina , El Sayed Abeer M 
Published: November 2011

AbstractBackgroundThis work aimed to study the homing evidence and the reparative effect of mesenchymal stem cells (MSCs) in the healing process of induced osteoarthritis in experimental animal model (donkeys).MethodsTwenty-seven donkeys were equally divided into 3 groups based on the observation period after induction of arthritis (3, 6 and 9 weeks) to achieve different degrees of osteoarthritis. Each group was subdivided into three subgroups of three animals each based on the follow-up period (1, 2 and 6 months) after treatment. The induction was done through intra-articular (IA) injection of 2 ml of Amphotericin-B in both carpal joints. MSCs were harvested in a separate procedure, labeled with green fluorescent protein (GFP) using monster GFP vector and suspended in hyaluronic acid for IA injection. Treatment approaches consisted of cell-treatment using MSCs suspended in 3 ml of hyaluronic acid (HA) for the right carpal joint; and using the same amount of (HA) but without MSCs for the left contralateral carpal joint to serve as a control. Animals were assessed clinically and radiologically before and after treatment. Synovial fluid was also evaluated. Histopathologically; articular cartilage structural changes, reduction of articular cartilage matrix staining, osteophyte formation, and subchondral bone plate thickening were graded. Data was summarized using median and percentile for scores of histopathologic grading. Comparison between groups was done using non-parametric Mann Whitney test.ResultsThe reparative effect of MSCs was significant both clinically and radiologically in all treated groups (P < 0.05) compared to the control groups. Fluorescence microscopy of sections of the cell-treated joints of all animals indicated that the GFP-transduced injected cells have participated effectively in the reparative process of the damaged articular surface and have integrated within the existing articular cartilage. The cells were associated with the surface of the cartilage and, were also detected in the interior.ConclusionsHoming was confirmed by the incorporation of injected GFP-labeled MSCs within the repaired newly formed cartilage. Significant recovery proves that the use of IA injection of autologous MSCs is a viable and a practical option for treating different degrees of osteoarthritis.http://www.biomedcentral.com/1741-7015/10/44/abstract