tbuckley/cabot-search huggingface dataset:
Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria
Authors: Hao Yu, Andreas Kistler, Mohd Hafeez Faridi, James Otto Meyer, Beata Tryniszewska, Dolly Mehta, Lixia Yue, Stuart Dryer, Jochen Reiser
Journal: Journal of the American Society of Nephrology (2016)

Gain-of-function mutations of classic transient receptor potential channel 6 (TRPC6) were identified in familial FSGS, and increased expression of wild-type TRPC6 in glomeruli is observed in several human acquired proteinuric diseases. Synaptopodin, an actin binding protein that is important in maintaining podocyte function, is downregulated in various glomerular diseases. Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6. We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes. Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it. Mechanistically, synaptopodin–dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons. Overexpression of wild–type or FSGS–inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6–mediated calcium influx and induced apoptosis. In vivo , knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6. Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice. Furthermore, administration of cyclosporin A reversed the LPS-induced increase in podocyte surface expression of TRPC6 in wild-type mice. Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction. Reducing TRPC6 surface levels may be a new approach to restoring podocyte function.
P1170 VIROLOGICAL RESPONSE AT WEEK 6 OF TELAPREVIR-BASED TRIPLE THERAPY IS THE MOST EFFECTIVE PREDICTOR OF CHRONIC HEPATITIS C TREATMENT OUTCOME
Authors: S. Hiramine, E. Ogawa, N. Furusyo, M. Nakamura, E. Kajiwara, H. Nomura, K. Dohmen, K. Takahashi, T. Satoh, K. Azuma, A. Kawano, Y. Tanabe, K. Kotoh, S. Shimoda, J. Hayashi
Journal: Journal of Hepatology (2014)
A Mechanism of Central Sleep Apnea in Patients with Heart Failure
Authors: S Javaheri
Journal: New England Journal of Medicine (1999)

Breathing is controlled by a negative-feedback system in which an increase in the partial pressure of arterial carbon dioxide stimulates breathing and a decrease inhibits it. Although enhanced sensitivity to carbon dioxide helps maintain the partial pressure of arterial carbon dioxide within a narrow range during waking hours, in some persons a large hyperventilatory response during sleep may lower the value below the apneic threshold, thereby resulting in central apnea. I tested the hypothesis that enhanced sensitivity to carbon dioxide contributes to the development of central sleep apnea in some patients with heart failure.
Ga-67 Inguinal Lymph Node Imaging in Patients With Sarcoidosis: A Third Typical Common Pattern
Authors: GEORGE C. PANOUTSOPOULOS, CHRISTOS BATSAKIS, GEORGIA TOURKOCHORITI, IOANNIS ILIAS, DIMITRIOS BOFOS, IOULIA CHRISTACOPOULOU
Journal: Clinical Nuclear Medicine (1998)

Seventy-eight consecutive whole body Ga-67 scintigrams of 74 patients with sarcoidosis were evaluated. The diagnosis of sarcoidosis was confirmed mainly by lymph node biopsies, and, in some patients, with skin, mucosal, lacrimal gland, salivary gland, and transbronchial lung biopsies, supported by typical x-ray findings or elevated SACE levels. The scintigrams were performed either during an initial diagnostic work-up or at follow-up after disease reactivation. In 32 patients (41%), inguinal lymph node uptake was seen. A symmetric bilateral inguinal lymph node pattern was seen in 25 patients (33%). This symmetric inguinal pattern was observed with typical Panda and/or Lambda patterns in 9 patients, with an atypical appearance in 13 patients, and with neither of these patterns in 3 patients. The typical symmetric inguinal lymph node Ga-67 uptake may help in the diagnosis of sarcoidosis, especially in cases of atypical Lambda and Panda patterns.
Abstract 5196: Granulocyte-colony stimulating factor (G-CSF) plays a causative role for H-Ras-mediated invasion and migration of human breast epithelial cells
Authors: SUN-HWA PARK, AREE MOON
Journal: Cancer Research (2010)

Abstract The whole human genome microarray on normal MCF10A, N-Ras-transformed, non-invasive MCF10A and H-Ras-transformed invasive MCF10A human breast epithelial cells revealed that the granulocyte-colony stimulating factor (G-CSF) was most highly upregulated in an H-Ras-specific manner. The present study investigated whether G-CSF plays a causative role for H-Ras-mediated MCF10A cell invasion and migration. Importantly, siRNA-mediated knockdown of G-CSF expression significantly reduced H-Ras-induced matrix metalloproteinase(MMP)-2 expression as well as invasion/migration. Activations of Rac1, MKK3/6 and p38 MAPK were inhibited by siRNA-knockdown of G-CSF. The induction of G-CSF expression conferred the invasive/migratory phenotype to parental MCF10A cells. Expression of MMP-2 and activation of signaling molecules Rac1, MKK3/6 and p38 MAPK were increased by G-CSF induction. Taken together, this study revealed G-CSF gene as a candidate marker for metastatic potential of breast epithelial cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5196.
Free online professional counselling service for children and teenagers with mental health problems is launched
Authors: M. Limb
Journal: BMJ (2013)

A new UK charity has launched an initiative to help children and teenagers with mental health problems, warning that “appalling” service cutbacks are depriving them of adequate support.

MindFull said that 11-17 year olds would be able to receive free online professional counselling, self help advice, and support in schools from trained peer mentors.

It said that an estimated 850 000 young people had a diagnosable mental health problem, equal to three children in every classroom, but almost 75% received no treatment.

One in five children, MindFull said, had had symptoms of depression, and almost a third of all children (32%) had thought about or attempted suicide before they were 16.

The new programme, which is part of the Beat Bullying …
Avid Ga-67 Uptake in Active Celiac Disease
Authors: PAUL A. THOMAS, AIDAN FOY
Journal: Clinical Nuclear Medicine (1999)

A 44-year-old woman was hospitalized because of severe leg edema, intermittent diarrhea, and weight loss. Initial evaluations showed an albumin level of 17 g/l. Duodenal biopsy showed total villous atrophy typical of celiac disease. The initial Ga-67 scan showed avid diffuse increased uptake in the abdomen. The patient responded well to a gluten-free diet, with increasing weight gain, resolution of her edema, and an increase in the serum albumin level to 38 g/l. Repeated Ga-67 scanning after treatment showed nearly complete resolution of the abdominal uptake.
SP0077 Identifying Key Elements in the Structure, Process and Outcome of Rehabilitation in Chronic Pain
Authors: M. Klokkerud
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Chronic pain is a major symptom in most rheumatic and musculoskeletal diseases, both inflammatory and non-inflammatory. When chronic pain leads to problems with coping and functioning in everyday life, rehabilitation is an important part of the health care service that should be provided. Most key elements of rehabilitation are independent of diagnosis and functional cause, like patient involvement, team organisation and goal orientation. In this lecture a framework for describing important elements of arthritis rehabilitation will be presented and used to explore the evidence of rehabilitation in patients with chronic pain. The framework, called the STAR-ETIC framework, was developed through a Delphi consensus procedure in a North-European expert group comprising patients, researchers and clinicians (The STAR-ETIC collaboration). The overall aim of developing the framework was to provide an instrument facilitating rigorous and congruent description of arthritis rehabilitation. The framework was based on 3 existing models that are well recognized within the field of rehabilitation: Wade9s rehabilitation model, ICF, and Donabedian9s healthcare model. What distinguish rehabilitation from other interventions and what are the key elements in the structure, process and outcome of rehabilitation in chronic pain? These questions will be shed light on in this lecture. <h3>References</h3> Klokkerud M, Hagen KB, Kjeken I, Bremander A, Hørslev-Petersen K, Vliet Vlieland T, Grotle M and the STAR-ETIC collaboration. Development of a framework identifying domains and elements of importance for arthritis rehabilitation. Journal of Rehabilitation Medicine 2012 May; 44(5):406-13. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6151
The Relative Efficacy of Guanethidine, Methyldopa and Pargyline as Antihypertensive Agents
Authors: John A. Oates, Arthur W. Seligmann, Melva A. Clark, Patricia Rousseau, Richard E. Lee
Journal: New England Journal of Medicine (1965)

A SIGNIFICANT advance in the treatment of moderate to malignant hypertension has been the development of potent agents that selectively impair adrenergic neuron transmission. The most frequently used drugs in this group currently are guanethidine, methyldopa and pargyline. Although they all act by interfering with adrenergic neuron function their pharmacologic mechanisms and clinical effects differ significantly. Despite these differences no previous study has compared the clinical effectiveness of these 3 agents, and those studies comparing 2 of them have been based on nonrandomized sequences and comparison under conditions that were not well defined.The purpose of this study was to . . .
THU0355 The Prevalence of Sleep Disorders and their Determinants in Patients with Chronic Neck Pain
Authors: S. Shyen, B. Amine, I. Binoune, S. Gueddari, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Assessing the quality of sleep and the prevalence of sleep disorders in patients with chronic neck pain and identify its determinants. <h3>Methods</h3> Cross-sectional study is conducted among patients, older than 18 years and followed for common chronic neck pain over 3 months, recruited at the consultation of Rheumatology. The Exclusion criteria were symptomatic neck pain and all chronic diseases or medication which can affect sleep. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) (0 = no disorder, 21 = major disorders) grouped into 7 items: subjective sleep quality, sleep latency, sleep duration,habituel sleep efficiency, sleep disturbances, use of sleeping medications and daytime dysfunction The characteristics of the neck pain were: the duration of the current episode, the presence of vertebral contractures or cervicobrachial neuralgia (NCB), the pain assessed by the visual analogue scale (VAS), functional disability assessed by the Neck disability index (NDI) French version validated, anxiety and depression assessed by Hospital Anxiety and Depression scale (HAD) Arabic version validated. A descriptive statistical analysis anda linear regression were performed <h3>Results</h3> 80 chronic neck pain patients were included, the average age of the patients was 51.7±11 years, with a female predominance (83.8%). The median evolution of neck pain was 24 months (12-48 months). The PSQI global score was elevated in 90% of our patients with a mean of 12±3.3. 85% of patients were poor sleepers,Participantsreported an average of 60 min needed tofall asleep each night (sleep latency).The mean hours of actualsleep per night was&lt;6 h (sleep duration). Sleep disorders were present in 85% of patients and a third of participants reported having pain at least three to four times a week. The use of sleeping medication was found in 31% of patients. Sleep difficulties causing a bad daytime functioning in 72% of patients. In univariate analysis, there is a positive relationship statistically significant between the PSQI total score and VAS pain (p=0.021, B =0.248, 95% CI [0.11, 0.129]),the duration of the current episode (p=0.05, B =0.214, 95% CI [-0.001, 0.50]) and the functional disability (NDI) (p=0.01, B =0.283, 95% CI [0.061, 0.456]). No association was found between sleep disorders and the presence of vertebral contractures or cervicobrachial neuralgia.After multivariate analysis, there is a positive relationship statistically significant between sleep disorders, VAS pain (p=0.029, B =0.237, 95% CI [0.003, 0.052]) and functional disability (p=0.042; B =0.247, 95% CI [0.009, 0.442]) <h3>Conclusions</h3> This study suggests that sleep disorders are common in patients with neck pain. This poor sleep is influenced by the intensity of the pain, which can alter their functional ability <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5326
THU0286 Imaging Findings in Osteoarticular Brucellosis:Study of Twelve Cases
Authors: H. Sahli, I. Cherif, R. Tekaya, O. Saidane, I. Mahmoud, L. Abdelmoula, R. Zouari
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The clinical and radiological diagnosis of osteoarticular brucellosis is not always easy owever essential for early and effective treatment. <h3>Objectives</h3> The aim of this study is to study radiological findings of osteoarticular brucellosis which were reported and confirmed in a rheumatological department. <h3>Methods</h3> This is a retrospective study which included medical records of patients treated for osteoarticular brucellosis during the ten past years [2002-2012]. Radiological data were recorded and analysed. <h3>Results</h3> Twelve cases of osteoarticular brucellosis were treated during the ten past years. All patients had spondylodiscitis. One patient had elbow bursitis associated. We had no case of peripheral arthritis or sacroiliitis. The mean age was 55 years (range 33 to 79 years) with a male to female ratio about 1. The predisposing conditions were present in 2 cases: diabetes mellitus and cirrhosis. Consumption of raw milk products was noted in 8 cases. The median duration from the onset of symptoms to the diagnosis was 3.6 months (range 1.5 to 6 months). The following symptoms were observed: inflammatory back pain (12 cases), sciatalgia with neurological signs (4 cases), weight loss (11 cases), fever (9 cases) and night sweating (n=7). One patient had symptom of spinal cord compression. C Reactive protein level was increased in 8 cases. Lymphopenia was noted in 4 cases. Wright serology was positive in all cases. Spondylodiscitis was uni-staged in all cases: the lumbar spine was the most commonly involved (8 cases). Standard X-ray showed narrowing of the intervertebral space (10 cases), endplate destruction (8 cases), bone condensation (1 case) and were normal in one case. MRI performed in all cases, had showed low signal intensity on T1-weighted images and high signal intensity on T2 weighted images of the vertebral bodies, endplates and intervertebral disc in all cases. Indeed the following findings were observed: paravertebral abcess formation (3 cases), epidural extension (8 cases), posterior longitudinal ligament elevation (1 case) and psoas abcess (2 cases). <h3>Conclusions</h3> MRIduring osteoarticular brucellosis and especially spondylodiscitis provides early diagnosis and well demonstration of paravertebral soft tissue spreading more than standard X-ray. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2759
AB0560 Evaluation of endothelial function in tocilizumab-treated rheumatoid arthritis patients refractory to TNF alfa inhibitors therapy
Authors: M. Covelli, A. Notarnicola, E. Lanciano, L. Coladonato, C. Rotondo, C. Di Teo, M. Locorotondo, C. Mandurino, A. Dachille, R. Carbonara, M.M. Ciccone, G. Lapadula
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cardiovascular disease is the major cause of excessive mortality in rheumatoid arthritis (RA). The endothelial dysfunction represents the earlier manifestation of Atherosclerosis and it predicts cardiovascular events. The effect of tumor necrosis factor alpha blockers and anti-CD20 (Rituximab) on endothelial function in RA patients has already been studied. It seems that both the anti-TNF alpha and Rituximab improved endothelial function after a 12-week treatment, even if the anti-TNF alpha effect is transient. The aim of the present study was to assess whether tocilizumab (anti-IL6) therapy affected the endothelial function in RA patients too. <h3>Objectives</h3> To evaluate endothelial function in Tocilizumab treated rheumatoid arthritis refractory to tumor-necrosis-factor alpha inhibitor theraphy. <h3>Methods</h3> Five consecutive RA patients (5 women; age range 38-51 years) without other cardiovascular risk factors were enrolled. These patients received intravenous tocilizumab every 28 days (mean of treatment 8,8 months). Flow-mediated endothelium-dependent vasodilatation (FMD%) was measured at day 0 prior to the tocilizumab infusion and at week 12 (before the infusion) by brachial ultrasonography. Normal range of FMD% value is between 5% and 10%. <h3>Results</h3> At week 12, FMD% values decreased in three out of five patients (mean ± SD 4,83±3,37%, range 2,46 - 11,89%); in one patient no FMD% values variation was found. On the contrary, in the other patient we observed an increase (range 3,94 - 5.62). In two out of three patients the decreased FMD% value was a little higher than the lower limit of normal; in the other one, it was less than 5% (2,46%). <h3>Conclusions</h3> Our study demonstrates an active effect of tocilizumab on endothelial function in RA patients refractory to TNFalpha blockers. Further data needs to establish what kind of effect on endothelial function is mediated by tocilizumab. <h3>Disclosure of Interest</h3> None Declared
Abstract 709: Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells
Authors: Beatrice E. Bachmeier, Peter H. Killian, Emanuel Kronski, Thomas Efferth
Journal: Cancer Research (2011)

Abstract Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate (ART), clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of ART in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, ART induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abolishment of apoptosis and cytotoxicity in pre-treated MDA-MB-231 cells. In contrast, ART was more cytotoxic towards the less tumorigenic MDA-MB-468 cells without showing resistance. Unraveling the underlying molecular mechanisms, we found that resistance was induced due to activation of the tumor progression related transcription factors NFκB and AP 1. Thereby transcription, expression and activity of the matrix-degrading enzyme MMP-1, whose function is correlated with increased invasion and metastasis, was up-regulated upon acquisition of resistance. Additionally, activation of the apoptosis-related factor NFκB lead to increased expression of ant-apoptotic bcl2 and reduced expression of pro-apoptotic bax. Application of ART in vivo in a model of xenografted breast cancer showed, that tumors growth was not efficiently abolished as compared to the control drug doxorubicin. Taken together our in vitro and in vivo results correlate well showing for the first time that ART induces resistance in highly metastatic breast tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 709. doi:10.1158/1538-7445.AM2011-709
Abstract 12237: Upregulation of Cardiac MicroRNA 34a, Sirt1, and Notch1 Following Oral Ingestion of Beetroot Juice and Doxorubicin Treatment: A Novel Protective Signaling Against Cardiotoxicity
Authors: Chang Yin, Shabina Rehman, Rakesh C Kukreja, Lei Xi
Journal: Circulation (2014)

Background: Beetroot juice (BRJ) is a dietary supplement containing high levels of nitrate and other nutrients. We previously reported that oral intake of BRJ protects against cardiotoxicity of doxorubicin (DOX) - a commonly used anticancer drug. BRJ diminished cell injury (indicated by serum level of cardiac troponin I) and ventricular dysfunction caused by DOX. The present study furhter investigates if BRJ modulates microRNA 34a (miR34a), a potent endogenous tumor suppressive molecule and its putative protein targets including Sirt1 (a well identified cardioprotective protein) and Notch1 (a major receptor for Notch signaling pathway that controls cell fate decision, including cell differentiation, proliferation, and death). Methods & Results: Adult male CF-1 mice were divided into 4 groups (n=3-4/group): 1. Saline (0.2 ml, IP); 2. DOX (15 mg/kg, IP); 3. BRJ (10 g BRJ extract was added into 1 liter of drinking water and provided for 13 days); and 4. BRJ+DOX (mice received BRJ for 7 days before DOX inject...
MIGRACIÓN ESPONTÁNEA DE PRÓTESIS METÁLICAS AUTOEXPANDIBLES TOTALMENTE RECUBIERTAS INSERTADAS POR COLEDOCOLITIASIS DIFÍCILES CON RESOLUCIÓN ESTABLE DE LA OBSTRUCCIÓN BILIAR
Authors: J García-Cano, T Martínez, L Valiente, Y Jiménez, R Martínez, M Viñuelas, C De Gracia, C Gómez, J Morillas, JI Pérez, Á Pérez
Journal: Endoscopy (2014)

Introducción: Tras una sesión de CPRE en la que no pueden extraerse todas las coledocolitiasis es habitual insertar algún tipo de prótesis plástica. Es conocido que tras varios meses las coledocolitiasis disminuyen de tamaño e incluso pueden desaparecer y la prótesis migrar.
Reduction of Solar Keratoses by Regular Sunscreen Use
Authors: Sandra C. Thompson, Damien Jolley, Robin Marks
Journal: New England Journal of Medicine (1993)

The incidence of and mortality from skin cancer are increasing in many countries. In view of the added concern about ozone depletion, many organizations are promoting the regular use of sunscreens to prevent skin cancer, despite the absence of evidence that these products have this effect. Solar (actinic) keratosis is a precursor of squamous-cell carcinoma of the skin.