tbuckley/cabot-search huggingface dataset:
ABC of arterial and venous disease: Renal artery stenosis
Authors: K. McLaughlin
Journal: BMJ (2000)

Renal artery stenosis is becoming increasingly common because of atherosclerosis in an ageing population. Patients usually present with hypertension and varying degrees of renal impairment, although silent renal artery stenosis may be present in many patients with vascular disease. Despite improvements in diagnostic and interventional techniques, controversy remains over whether, when, and how to revascularise the kidneys of patients with renal artery stenosis. #### Charac teristics of renal artery stenosis ##### Fibromuscular dysplasia ##### Atherosclerosis The pathophysiology of unilateral renal artery stenosis provides a clear example of how hypertension develops. Narrowing of the renal artery, due to atherosclerosis or, rarely, fibromuscular dysplasia, leads to reduced renal perfusion. The consequent activation of the renin-angiotensin system causes hypertension (mediated by angiotensin II), hypokalaemia, and hyponatraemia (which are features of secondary hyperaldosteronism). Although these features may be reversed by correcting the stenosis, a classic presentation is uncommon, and hypertension is rarely cured in patients with atheromatous renal artery stenosis. In addition, it is now known that renal artery stenosis is underdiagnosed and may present as a spectrum of disease from secondary hypertension to end stage renal failure, reflecting variation in the underlying disease process. Thus, the presence of overt, or coincidental, renal artery stenosis usually reflects widespread vascular disease, with the associated implications for cardiovascular risk and patient survival. Atheromatous lesions may affect different sized vessels within the kidney, and multiple lesions may exist. The site limits the potential for revascularisation; only lesions within the large vessels are amenable. The commonest site, at the ostium of the renal artery, is more effectively treated by stenting. Ulcerated atheromatous plaques may also generate cholesterol microemboli (particularly after vascular intervention) #### Prevalence of atheromatous renal artery stenosis
Psoriasis and cardiovascular disease: another contribution in the hierarchy of evidence
Authors: A.B. Kimball
Journal: British Journal of Dermatology (2012)

Conflicts of interest The author is a consultant and investigator for Amgen, Jansen, Abbott, Pfizer, Merck, Vascular Biogenics Labs, Celgene and Idera. ORIGINAL ARTICLE, p 1345 The observation that patients with moderate‐to‐severe psoriasis are more likely to be overweight or obese was first made decades ago,1 and the corollary that these patients were consequently at increased cardiovascular risk soon followed. However, initial studies were largely carried out in hospitalized patients or in specialized care settings with limited generalizability. With the advent of large patient care databases and registries, an increasing number of authors have confirmed that patients with psoriasis, especially those with moderate‐to‐severe disease, are indeed at increased risk for cardiovascular events and have a higher level of risk factors, such as obesity and hypertension, than comparator populations. As a further observation, however, the preponderance of analyses has also suggested that psoriasis itself, like other autoimmune conditions such as rheumatoid arthritis (RA), confers an independent additional risk.2 The article by Xu and Zhang et al.,3 in this issue of BJD confirms that, although this finding has not been duplicated in all studies, the general conclusion stands using meta‐analyses of available work. That said, the hypothesis still needs to be examined for biological plausibility and for the limitations that are inherent in the use of large datasets and meta‐analyses.
Guidelines of care for the management of psoriasis and psoriatic arthritis
Authors: Alan Menter, Neil J. Korman, Craig A. Elmets, Steven R. Feldman, Joel M. Gelfand, Kenneth B. Gordon, Alice Gottlieb, John Y.M. Koo, Mark Lebwohl, Henry W. Lim, Abby S. Van Voorhees, Karl R. Beutner, Reva Bhushan
Journal: Journal of the American Academy of Dermatology (2009)
H1N1 influenza in lung transplant patients: A follow up after one year
Authors: Harish Seethamraju, Bindu Akkanti, Amit Parulekar, Goutham Dronavalli, Matthias Loebe, Saverio LaFrancesca, George Noon, Karolina Chmielowiec, Pawel Kolodziejski
Journal: European Respiratory Journal (2011)

The 2009 outbreak of H1N1 caused significant morbidity and mortality. Long term outcome of H1N1 in lung transplant (LT) patients have not been well characterized.  We did a retrospective study of LT patients diagnosed with H1N1 between July and November 2009. Data pertaining to LT, history of influenza, admission information, pulmonary function, radiograph, computer tomography scans, and echocardiograms were identified.  Among 181 LT patients, there were 10 PCR confirmed cases of H1N1. Patients had a median of 4 months time since LT to infection, received immunosuppressive therapy, and had not received vaccination against H1N1. 60% of patients presented with fever and cough, others had non-pulmonary complaints and all received oseltamivir upon diagnosis. Consolidation was seen by imaging in 60% of patients. Median FEV1 decreased and remained low over a one-year follow up period (1.72 – 1.51 – 1.54) despite clinical improvement. Two patients progressed to respiratory failure and severe LV dysfunction (EF 20-30%) despite previous normal LV function. These patients were on ECMO and had improvement in cardiac and respiratory status but developed gangrene, vascular necrosis, sepsis, and died. One patient developed acute rejection and two patients developed chronic rejection with one retransplanted in February 2010.  LT patients contracting H1N1 infection have significant morbidity ranging from mild disease to severe respiratory failure with cardiac dysfunction. Rapidly deteriorating patients had developed myocardial dysfunction, but continued to decline even when this dysfunction resolved. Increased incidence of chronic rejection and extended decreased pulmonary function is seen among LT patients infected with H1N1.
Clinical exercise testing with reference to lung diseases: indications, standardization and interpretation strategies. ERS Task Force on Standardization of Clinical Exercise Testing. European Respiratory Society
Authors: J. Roca, B.J. Whipp, A.G.N. Agusti, S.D. Anderson, R. Casaburi, J.E. Cotes, C.F. Donner, M. Estenne, H.T.M. Folgering, T. Higenbottam, K. Kilian, P. Palange, A. Patessio, C. Prefaut, R. Sergysels, P. Wagner, I. Weisman
Journal: European Respiratory Journal (1997)
Galectin-1 Protein Therapy Prevents Pathology and Improves Muscle Function in the mdx Mouse Model of Duchenne Muscular Dystrophy
Authors: Pam M Van Ry, Ryan D Wuebbles, Megan Key, Dean J Burkin
Journal: Molecular Therapy (2015)

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by mutations in the dystrophin gene, leading to the loss of a critical component of the sarcolemmal dystrophin glycoprotein complex. Galectin-1 is a small 14 kDa protein normally found in skeletal muscle and has been shown to be a modifier of immune response, muscle repair, and apoptosis. Galectin-1 levels are elevated in the muscle of mouse and dog models of DMD. Together, these findings led us to hypothesize that Galectin-1 may serve as a modifier of disease progression in DMD. To test this hypothesis, recombinant mouse Galectin-1 was produced and used to treat myogenic cells and the mdx mouse model of DMD. Here we show that intramuscular and intraperitoneal injections of Galectin-1 into mdx mice prevented pathology and improved muscle function in skeletal muscle. These improvements were a result of enhanced sarcolemmal stability mediated by elevated utrophin and α7β1 integrin protein levels. Together our results demonstrate for the first time that Galectin-1 may serve as an exciting new protein therapeutic for the treatment of DMD. Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by mutations in the dystrophin gene, leading to the loss of a critical component of the sarcolemmal dystrophin glycoprotein complex. Galectin-1 is a small 14 kDa protein normally found in skeletal muscle and has been shown to be a modifier of immune response, muscle repair, and apoptosis. Galectin-1 levels are elevated in the muscle of mouse and dog models of DMD. Together, these findings led us to hypothesize that Galectin-1 may serve as a modifier of disease progression in DMD. To test this hypothesis, recombinant mouse Galectin-1 was produced and used to treat myogenic cells and the mdx mouse model of DMD. Here we show that intramuscular and intraperitoneal injections of Galectin-1 into mdx mice prevented pathology and improved muscle function in skeletal muscle. These improvements were a result of enhanced sarcolemmal stability mediated by elevated utrophin and α7β1 integrin protein levels. Together our results demonstrate for the first time that Galectin-1 may serve as an exciting new protein therapeutic for the treatment of DMD.
Incidence and characterization of MLL gene (11q23) rearrangements in acute myeloid leukemia M1 and M5
Authors: H Poirel, K Rack, E Delabesse, I Radford-Weiss, X Troussard, C Debert, D Leboeuf, C Bastard, F Picard, A Veil-Buzyn, G Flandrin, O Bernard, E Macintyre
Journal: Blood (1996)
Abstract 1708: Heparanase regulates response to chemotherapy in myeloma
Authors: Vishnu Prakash C. Ramani, Fenghuang Zhan, Guido Tricot, Ralph D. Sanderson
Journal: Cancer Research (2014)

Abstract Following therapy, essentially all multiple myeloma patients relapse due to a population of chemoresistant cells leading to eventual patient death. Our lab has identified heparanase, an endoglycosidase, as a master regulator of aggressive myeloma disease. In the present study that was designed to probe the role of heparanase in chemoresistance, we made the striking finding that heparanase promotes survival of tumor cells post-therapy. Using an array of cellular viability assays, we tested for differences in viability and apoptosis between myeloma cells engineered to express high levels of heparanase (HPSE-high) and cells expressing low levels of heparanase (HPSE-low) following their exposure to frontline anti-myeloma drugs (bortezomib, carfilzomib). Results revealed a much smaller apoptotic fraction and higher cell viability following treatment of the HPSE-high cells compared to HPSE-low cells. In addition to promoting tumor survival, we also discovered that myeloma cell expression and secretion of heparanase is dramatically enhanced in response to chemotherapy. Using small molecule inhibitors, we were able to pinpoint that activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was driving the heparanase expression upon chemotherapy. The secreted heparanase generated by chemotherapy was readily taken up by tumor cells growing in culture, consistent with previous studies demonstrating that heparanase is taken up by myeloma tumor cells and that this activates aggressive tumor behavior. Extending our findings to the clinic revealed that in tumor cells from seven out of nine myeloma patients examined, there was a dramatic increase in heparanase gene expression following chemotherapy. Together, these results demonstrate a pivotal role for heparanase in regulating myeloma response to therapy and indicate that the use of heparanase inhibitors may inhibit or delay relapse in myeloma. Citation Format: Vishnu Prakash C. Ramani, Fenghuang Zhan, Guido Tricot, Ralph D. Sanderson. Heparanase regulates response to chemotherapy in myeloma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1708. doi:10.1158/1538-7445.AM2014-1708
Abstract 17014: The Impact of Risk Score (CHADS2 versus CHADS2-Vasc) on Long-term Outcomes After Atrial Fibrillation Ablation
Authors: Victoria Jacobs, Heidi T May, Tami L Bair, Brian G Crandall, Michael Cutler, J. P Weiss, Jeffrey S Osborn, Charles Mallendar, John D Day, Thomas J Bunch
Journal: Circulation (2014)

Background: Risk stratification tools are needed to better select candidates for catheter ablation of atrial fibrillation (AF). Both the CHADS2 and CHADS2-VASC scores have utility in predicting AF-related outcomes and guiding anticoagulation treatment. We sought to determine if these risk scores predict long-term outcomes after AF ablation and if one risk score provides comparative superior performance. Methods: CHADS2 and CHADS2-VASC scores were calculated in 2179 AF ablation patients enrolled into Intermountain Heart Collaborative Study. CHADS2 and CHADS2-VASC were categorized by recursive partitioning categories as CHADS2: 0-1, 2-4, and &gt;4 and CHADS2-VASC: 0-2, 2-5, &gt;5. Patient outcomes were analyzed over 5 years for AF/Aflutter recurrence and MACE (death, stroke, heart failure hospitalization and AF/Aflutter recurrence). Results: Average age was 65.7±10.5 years and 61.1% were male. Both scores incrementally predicted risk of AF recurrence, stroke, heart failure, and death at 5 years (Figure). Increasing CHADS2 (hazard ratio [HR] =1.19, p&lt;0.001) and CHADS2-VASC (HR=1.15, p&lt;0.0001) scores were both associated with AF/Aflutter recurrence. Results were similar for MACE: with increasing CHADS2 (HR=1.20, p&lt;0.0001) and CHADS2-VASC (HR=1.15, p&lt;0.0001) scores associated with risk. When CHADS2 and CHADS2-VASC were modeled simultaneously, only CHADS-VASC significantly predicted AF recurrence (HR=1.13, p=0.001) and MACE (HR=1.13, p=0.001). Conclusion: Both the CHADS2 and CHADS2-VASC scores were excellent in stratifying patients for 5-year outcomes after AF ablation. However, the CHADS2-VASC score was superior to CHADS2 when accounting for all baseline variables for predicting both AF recurrence and AF-related morbidities.
Abstract 3632: Targeting of tumor myeloid suppressor cells by Salmonella bacteria causes a shift to M1 phenotype and leads to inhibition of tumor growth
Authors: Basel K. Al-Ramadi, Suneesh Kaimala, Yassir A. Mohamed, Jincy M. Issac, Eyad Elkord, Salem Chouaib, Maria J. Fernandez-Cabezudo
Journal: Cancer Research (2014)

Abstract Tumor development is associated with changes in hematopoiesis that lead to an increase in myelomonocytic cells in systemic sites as well as within the tumor tissue. The accumulation of myeloid cells within tumors not only promotes angiogenesis and tissue remodeling required for tumor growth but also maintains the tumor milieu as an immunosuppressive environment. We have previously shown that attenuated strains of the facultative anaerobic bacteria, Salmonella enterica serovar Typhimrium, can effectively retard tumor growth in a therapeutic melanoma model. Given that Salmonella organisms utilize host macrophages as their primary niche for survival, we investigated the consequences of Salmonella treatment on myeloid cell recruitment, phenotypic characteristics and functional activation within tumor tissue of B16.F1 melanoma-bearing animals. Treatment with Salmonella led a preferential expansion, within spleen and tumor tissues, of CD11b+Gr-1+, but not CD11b+Gr-1-, myeloid cells. Using 6-color FACS analysis, CD11b+Gr-1+ cells were shown to exhibit significant up-regulation in the expression of activation markers, including MHC class II, CD80, and Sca-1/Ly6A proteins. Moreover, the functional activities of total tumor infiltrating cells or CD11b-purified cells from tumor tissue were assessed by qRT-PCR. Salmonella treatment induced a dramatic increase in iNOS and IFN-g gene expression but inhibited ARG1 and IL-4 genes. Further, while expression of TGF-b and VEGF was reduced, the level of inflammation-related S100A9 gene was increased. Our findings demonstrate that systemic administration of attenuated Salmonella leads to phenotypic and functional changes in tumor myeloid suppressor cells, with a shift from a predominantly M2 phenotype to an activated, effector macrophage phenotype. Citation Format: Basel K. Al-Ramadi, Suneesh Kaimala, Yassir A. Mohamed, Jincy M. Issac, Eyad Elkord, Salem Chouaib, Maria J. Fernandez-Cabezudo. Targeting of tumor myeloid suppressor cells by Salmonella bacteria causes a shift to M1 phenotype and leads to inhibition of tumor growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3632. doi:10.1158/1538-7445.AM2014-3632
Abstract P105: Small Magnitude of the Heart Movement Due to Respiration is Associated With Sudden Cardiac Death
Authors: Muammar M Kabir, Elyar Ghafoori, Jonathan W Waks, Sunil K Agarwal, Dan E Arking, Nona Sotoodehnia, David S Siscovick, Wendy Post, Charles Henrikson, Scott D Solomon, Elsayed Z Soliman, Josef Coresh, Mark E Josephson, Larisa G Tereshchenko
Journal: Circulation (2015)

Background: Respiration causes heart movement in the chest and proportional change in the heart’s electrical axis. The ECG can be used to measure respiration-related heart motion. The effect of respiration on the ECG is usually considered an artifact. However, it is unknown whether pattern of heart motion due to respiration holds any prognostic value. Method: After excluding those with atrial fibrillation, or atrial or ventricular premature contractions at baseline visit, 14613 ARIC cohort participants (mean age 54.0±5.8 y; 6595 [45.1%] men; 10744 [73.5%] white, 1311 [9.0%] with prevalent cardiovascular disease (CVD)) were included. The digital resting ECG was analyzed using custom Matlab software. The absolute magnitude of the displacement of the heart due to respiration was calculated on X (left-right), Y (up-down), and Z (anterior-posterior) axes. Sudden cardiac death (SCD) and non-coronary heart disease (CHD) death served as competing outcomes in our analysis. Results: In CVD-free participants (as compared to prevalent CVD group) heart moved more on X axis (137±46 vs. 128±47 μV; P&lt;0.0001), and less on Z axis (123±52 vs. 127±60 μV; P=0.05). During a median follow-up of 14 years 278 SCDs (96 in CVD group) and 1619 non-CHD (279 in CVD group) deaths occurred. In competing risk analysis that adjusted for age, gender, race, history of myocardial infarction, CHD, heart failure, systolic blood pressure, anti-hypertensive medications, diabetes, smoking, total cholesterol, high density lipoprotein, level of physical activity, use of beta-blockers, left ventricular hypertrophy on ECG and QRS duration, the absolute magnitude of respiration-related heart movement on X axis (SHR 0.74; 95%CI 0.59-0.93; P=0.009) and Z axis (SHR 1.19; 95%CI 1.01-1.41; P=0.042) associated with SCD (but not with non-CHD death) in CVD group, but not in CVD-free participants. Conclusion: Greater respiration-caused heart motion on Z axis and smaller - on X axis likely reflects cardiomegaly and is associated with increased risk of SCD in patients with CVD.
Eat me!
Authors: Alison Mitchell
Journal: Nature reviews. Immunology (2002)

Dying cells are a danger to their healthy neighbours, and must be rapidly cleared away.This task is carried out by phagocytes, which recognize and then engulf the apoptotic cells.The 'eat-me' signal for phagocytes has been proposed to be phosphatidylserine (PS), which is exposed on the surface of dying cells.But how is this signal read by phagocytes?Reporting in Nature, Shigekazu Nagata and colleagues now describe a factor that could act as a bridge between the dying cells and the phagocytes.They isolated this protein -the milk fat globule-EGF-factor 8 (MFG-E8) -while searching for factors that mediate the engulfment of apoptotic cells by macrophages (a type of phagocytic cell).The authors started by using activated mouse macrophages to immunize Armenian hamsters, from which they prepared a series of antibodies.One of these -designated 2422increased the percentage of macrophages that engulfed apoptotic cells.Nagata and colleagues then used immunoprecipitation followed by affinity purification to identify the target of 2422, and found it to be two isoforms of MFG-E8.A purified recombinant form of the larger isoform (MFG-E8-L) did not bind to freshly isolated thymocytes, but it could bind to thymocytes if they were first treated with dexamethasone (which induces apoptosis).How does MFG-E8-L recognize these apoptotic cells?Annexin V is known to bind PS, but pretreatment with MFG-E8-L reduced this interaction (and vice versa), which indicates that MFG-E8-L recognizes PS on the apoptotic cells.But this doesn't explain how the MFG-E8-L then interacts with phagocytes.The authors noticed, however, that MFG-E8-L contains an arginine-glycine-aspartate (RGD) motif, which can be recognized by
Complete molecular remissions induced by patient-specific vaccination plus granulocyte–monocyte colony-stimulating factor against lymphoma
Authors: Maurizio Bendandi, Christopher D. Gocke, Carol B. Kobrin, Floyd A. Benko, Lars A. Sternas, Robin Pennington, Thelma M. Watson, Craig W. Reynolds, Barry L. Gause, Patricia L. Duffey, Elaine S. Jaffe, Stephen P. Creekmore, Dan L. Longo, Larry W. Kwak
Journal: Nature Medicine (1999)
Book: Tropical Medicine in the Twentieth Century
Authors: G. Cowan
Journal: BMJ (1999)

Helen J Power Kegan Paul International, £45, pp 284 ISBN 0 7103 0604 0 Rating: ![Graphic][1]</img>![Graphic][2]</img> “Tropical medicine as a formal discipline is dead and should be buried” was the motion proposed by Gordon Cook at the Royal Society of Tropical Medicine in October 1996. Although the 20th edition of Manson's Tropical Diseases had just been published under his editorship, with his hopes that it would remain the “bible” of tropical medicine, Cook made the case for the demise of the old “colonial” discipline based largely on protozoal and helminthic diseases and the recognition of “medicine of the tropics,” which includes many non-infectious problems and particular aspects … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
1,25-Dihydroxyvitamin D3 Induces Differentiation of a Retinoic Acid–Resistant Acute Promyelocytic Leukemia Cell Line (UF-1) Associated With Expression of p21WAF1/CIP1 and p27KIP1
Authors: Akihiro Muto, Masahiro Kizaki, Kenji Yamato, Yohko Kawai, Maiko Kamata-Matsushita, Hironori Ueno, Masahiro Ohguchi, Tatsuji Nishihara, H. Phillip Koeffler, Yasuo Ikeda
Journal: Blood (1999)
Abstract 16448: Matricellular Activation of CD47 Promotes Pulmonary Arterial Hypertension by Regulating Cellular Homolog of the V-Myconcogene
Authors: Natasha Rogers, Mingyi Yao, Maryam Sharifi, Claudette St Croix, Jeffrey Isenberg
Journal: Circulation (2014)

Introduction: Pulmonary arterial hypertension (PAH) remains progressive and incurable. There is currently a deficit in understanding the mechanisms that drive PAH. Recently, we reported that the matricellular protein thrombospondin-1 (TSP1) is induced in pre-clinical models of PAH and human disease. However, the role of its receptor, CD47, in PAH is unknown. Methods: Age-matched male wild type (WT) and CD47-/- mice were challenged with chronic hypoxia (10% FiO2 for 3 weeks). Age-matched Sprague Dawley rats received monocrotaline for 2 weeks followed by CD47 blocking or isotype control antibody. At the end of treatment all animals underwent cardio-pulmonary and biomolecular analysis. Human, and murine WT and CD47-/- pulmonary endothelial and vascular cells were also studied. Results: Mice lacking CD47 are resistant to hypoxia-mediated PAH with minimal evidence of pulmonary arterial overgrowth and no right ventricular hypertrophy compared to controls. Hypoxic CD47-/- mice demonstrated increased stroke volum...