tbuckley/cabot-search huggingface dataset:
Clinical Features of Anti-Factor H Autoantibody–Associated Hemolytic Uremic Syndrome
Authors: Marie-Agnès Dragon-Durey, Sidharth Kumar Sethi, Arvind Bagga, Caroline Blanc, Jacques Blouin, Bruno Ranchin, Jean-Luc André, Nobuaki Takagi, Hae Cheong, Pankaj Hari, Moglie Le Quintrec, Patrick Niaudet, Chantal Loirat, Wolf Herman Fridman, Véronique Frémeaux-Bacchi
Journal: Journal of the American Society of Nephrology (2010)

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy that associates, in 70% of cases, with genetic or acquired disorders leading to dysregulation of the alternative pathway of complement. Autoantibody directed against Factor H causes at least 6% to 10% of aHUS cases, but only a few clinical reports are available. Here, we describe the clinical, biologic, genetic features, treatment, and outcome of 45 patients who presented with aHUS associated with anti-FH autoantibody. We found that this form of aHUS primarily affects children between 9 and 13 years old but it also affects adults. It presents with a high frequency of gastrointestinal symptoms and with extrarenal complications and has a relapsing course. Activation of the alternative pathway of complement at the onset of disease portends a poor prognosis. Early specific treatment may lead to favorable outcomes. These data should improve the recognition and diagnosis of this form of aHUS and help identify patients at high risk of a poor outcome.
Effect of split exercise sessions on excess post-exercise oxygen consumption.
Authors: L A Kaminsky, S Padjen, J LaHam-Saeger
Journal: British Journal of Sports Medicine (1990)

In this study the excess post-exercise oxygen consumption (EPOC), and related metabolic measures, following a 50 minute run compared to two 25 minute runs all at 70 per cent of peak VO2 in six women were investigated. Open-circuit spirometry procedures were used and appropriate control conditions were maintained for all trials. Following exercise, VO2 returned to baseline within 30 minutes for all three exercise trials. Magnitude of EPOC was also similar after all runs. However, the combined magnitude (expressed in kcals) of the two 25 minute runs was significantly greater than the continuous 50 minute run (13.88 vs 6.39). Heart rate remained elevated above baseline, and respiratory exchange ratio was lower than baseline 30 minutes after exercise. It is concluded that split exercise sessions can significantly increase post-exercise caloric expenditure. However, the overall magnitude of the increase is small.
Allergy to Tremonil
Authors: M. B. Carson
Journal: BMJ (1964)

complication which I find fairly frequently -namely, pain in the right subcostal area.I feel certain that it is a manifestation of change in the biliary system, but it is not a colic, the pain being dull and steady with tenderness in the same area.One patient had an area of paraesthesia in addition.It tends to continue intermittently throughout the prenatal course and disappears after delivery.To date I have found no good explanation for it, or method of relieving it, other than by using analgesics.-Iam, etc.,
Thinking Inside the Box
Authors: Peter Jessel, Nasia Safdar, W. Joseph McCune, Sanjay Saint, Daniel R. Kaul
Journal: New England Journal of Medicine (2010)

A 62-year-old woman presented to a community hospital with nausea, vomiting, diarrhea, and fever, all of 1 week's duration. She had a history of psoriasis and psoriatic arthritis, hypertension, hyperlipidemia, possible fibromyalgia, and degenerative lumbar disk disease.
Prolyl Isomerase Cyclophilin A Regulation of Janus-Activated Kinase 2 and the Progression of Human Breast Cancer
Authors: Jiamao Zheng, Jennifer E. Koblinski, Laura V. Dutson, Yvonne B. Feeney, Charles V. Clevenger
Journal: Cancer Research (2008)

Abstract The activation of the Janus-activated kinase 2 (Jak2) tyrosine kinase following ligand binding has remained incompletely characterized at the mechanistic level. We report that the peptidyl-prolyl isomerase (PPI) cyclophilin A (CypA), which is implicated in the regulation of protein conformation, is necessary for the prolactin (PRL)-induced activation of Jak2 and the progression of human breast cancer. A direct correlation was observed between the levels or activity of CypA and the extent of PRL-induced signaling and gene expression. Loss of PRLr-CypA binding, following treatment with the PPI inhibitor cyclosporine A (CsA), or overexpression of a dominant-negative PRLr mutant (P334A) resulted in a loss of PRLr/Jak2–mediated signaling. In vitro, CsA treatment of breast cancer cells inhibited their growth, motility, invasion, and soft agar colony formation. In vivo, CsA treatment of nude mice xenografted with breast cancer cells induced tumor necrosis and completely inhibited metastasis. These studies reveal that a CypA-mediated conformational change within the PRLr/Jak2 complex is required for PRL-induced transduction and function and indicate that the inhibition of prolyl isomerases may be a novel therapeutic strategy in the treatment of human breast cancer. [Cancer Res 2008;68(19):7769–78]
Inhibition of Atherosclerosis Development in Cholesterol-Fed Human Apolipoprotein A-I–Transgenic Rabbits
Authors: Nicolas Duverger, Howard Kruth, Florence Emmanuel, Jean-Michel Caillaud, Ce´line Viglietta, Graciela Castro, Anne Tailleux, Catherine Fievet, Jean Charles Fruchart, Louis Marie Houdebine, Patrice Denefle
Journal: Circulation (1996)

Background Prospective epidemiological studies support the hypothesis that high levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I limit atherosclerosis development. However, more data from studies with animal models of atherosclerosis that resemble the human disease are required to demonstrate the effect of apo A-I in the inhibition of atherogenesis. The rabbit is a good animal model for human atherosclerosis. Methods and Results Human apo A-I–transgenic rabbits have been produced, and we have evaluated the effect of apo A-I on the development of atherosclerosis in transgenic rabbits fed a cholesterol-rich diet for 14 weeks. Plasma cholesterol levels of atherogenic apo B-containing lipoproteins were similar for transgenic and control rabbits (&gt;1000 mg/dL), while plasma levels of HDL cholesterol in the transgenic group were always about twice that of the control group (68±11 versus 37±3 mg/dL at 14 weeks; P &lt;.001). At the end of the experiment, the amount of aortic surface area covered by lesions as well as the amount of lipid accumulation in the aorta were significantly less in transgenic rabbits compared with the control group (15±12% versus 30±8%, P &lt;.0027 for the surface area of the thoracic aorta; 116±31 versus 247±39 μmol/g aorta, P &lt;.0068 for cholesterol content in total aorta). Conclusions Overexpression of human apo A-I in rabbits inhibits the development of atherosclerosis in this animal model that resembles, in many respects, human atherosclerosis.
Sustained HBs seroconversion during lamivudine and adefovir dipivoxil combination therapy for lamivudine failure
Authors: Marianne Maynard, Parviz Parvaz, Sandra Durantel, Michèle Chevallier, Philippe Chevallier, Muriel Lot, Christian Trepo, Fabien Zoulim
Journal: Journal of Hepatology (2004)
A Core Human Primary Tumor Angiogenesis Signature Identifies the Endothelial Orphan Receptor ELTD1 as a Key Regulator of Angiogenesis
Authors: Massimo Masiero, Filipa Costa Simões, Hee Dong Han, Cameron Snell, Tessa Peterkin, Esther Bridges, Lingegowda S. Mangala, Sherry Yen-Yao Wu, Sunila Pradeep, Demin Li, Cheng Han, Heather Dalton, Gabriel Lopez-Berestein, Jurriaan B. Tuynman, Neil Mortensen, Ji-Liang Li, Roger Patient, Anil K. Sood, Alison H. Banham, Adrian L. Harris, Francesca M. Buffa
Journal: Cancer Cell (2013)

Limited clinical benefits derived from anti-VEGF therapy have driven the identification of new targets involved in tumor angiogenesis. Here, we report an integrative meta-analysis to define the transcriptional program underlying angiogenesis in human cancer. This approach identified ELTD1, an orphan G-protein-coupled receptor whose expression is induced by VEGF/bFGF and repressed by DLL4 signaling. Extensive analysis of multiple cancer types demonstrates significant upregulation of ELTD1 in tumor-associated endothelial cells, with a higher expression correlating with favorable prognosis. Importantly, ELTD1 silencing impairs endothelial sprouting and vessel formation in vitro and in vivo, drastically reducing tumor growth and greatly improving survival. Collectively, these results provide insight into the regulation of tumor angiogenesis and highlight ELTD1 as key player in blood vessel formation.
Interleukin 4 activates a signal transducer and activator of transcription (Stat) protein which interacts with an interferon-gamma activation site-like sequence upstream of the I epsilon exon in a human B cell line. Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat.
Authors: X Fenghao, A Saxon, A Nguyen, Z Ke, D Diaz-Sanchez, A Nel
Journal: Journal of Clinical Investigation (1995)

Germ line C transcripts can be induced by IL-4 in the human B cell line, BL-2. Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon, we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells. This factor was designated IL-4 NAF (IL-4-induced nuclear-activating factors) and was identified as a tyrosine phosphoprotein, which translocates from the cytosol to the nucleus upon IL-4 treatment. Because these are the characteristics of a signal transducer and activator of transcription (Stat) protein, we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat, also known as Stat6, but not antibodies to other Stat proteins, interfere with the formation of the IL-4 NAF complex. Congruous with the involvement of a Stat protein, IL-4 induced robust Janus kinase 3 (JAK3) activity in BL-2 cells. Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAF in electrophoretic mobility shift assay. These results show that IL-4 NAF is IL-4 Stat, which is activated by JAK3 in response to IL-4 receptor engagement.
Performance of the Chronic Kidney Disease Epidemiology Collaboration Equation to Estimate Glomerular Filtration Rate in Diabetic Patients
Authors: Nicolas Rognant, Sandrine Lemoine, Martine Laville, Aoumeur Hadj-Aïssa, Laurence Dubourg
Journal: Diabetes Care (2011)

The best method to estimate glomerular filtration rate (GFR) in diabetic patients is still largely debated. We compared the performance of creatinine-based formulas in a European diabetic population.We compared the performance of Cockcroft and Gault, simplified Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equations in 246 diabetic patients by calculating the mean bias and the interquartile range (IQR) of the bias, 10% (P10) and 30% (P30) accuracies, and Bland-Altman plots. GFR was measured by inulin clearance.For the whole population, the IQR was slightly lower for CKD-EPI, but the mean bias was lower and P10 and P30 were higher for MDRD. Similar results were observed in specific subgroups, including patients with mild renal insufficiency, obese patients, or type 2 diabetic patients.In our population, the CKD-EPI formula does not exhibit better performance than the simplified MDRD formula for estimating GFR.
NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia
Authors: Shinya Kimura, Haruna Naito, Hidekazu Segawa, Junya Kuroda, Takeshi Yuasa, Kiyoshi Sato, Asumi Yokota, Yuri Kamitsuji, Eri Kawata, Eishi Ashihara, Yohei Nakaya, Haruna Naruoka, Tatsushi Wakayama, Kimio Nasu, Tetsuo Asaki, Tomoko Niwa, Kazuko Hirabayashi, Taira Maekawa
Journal: Blood (2005)
Negative epistasis between the malaria-protective effects of α+-thalassemia and the sickle cell trait
Authors: Thomas N Williams, Tabitha W Mwangi, Sammy Wambua, Timothy E A Peto, David J Weatherall, Sunetra Gupta, Mario Recker, Bridget S Penman, Sophie Uyoga, Alex Macharia, Jedidah K Mwacharo, Robert W Snow, Kevin Marsh
Journal: Nature Genetics (2005)
THE EFFECT OF X-RADIATION ON THE MULTIPLICATION OF RICKETTSIA MOOSERI IN EMBRYONATE EGGS
Authors: Donald Greiff, Masahiro Chiga, Herman T. Blumenthal, Henry Pinkerton
Journal: The Journal of Experimental Medicine (1953)

The multiplication of Rickettsia mooseri in fertile eggs is speeded up and quantitatively increased by single dose x-radiation given either 24 hours before or 48 hours after inoculation. This effect is noted at all dosage levels studied, ranging from 100 to 1500 r. The rickettsiostatic effects of high incubation temperature (40 degrees C.) and of streptomycin are neutralized by radiation, but the rickettsiostatic actions of PABA, penicillin, and aureomycin are not altered. Possible mechanisms of action and implications of the observed effects are discussed.
Dietary ω-3 Polyunsaturated Fatty Acid Intake and Risk for Amyotrophic Lateral Sclerosis
Authors: Kathryn C. Fitzgerald, Éilis J. O’Reilly, Guido J. Falcone, Marjorie L. McCullough, Yikyung Park, Laurence N. Kolonel, Alberto Ascherio
Journal: JAMA Neurology (2014)

Amyotrophic lateral sclerosis (ALS) is a severe progressive disease that cannot be prevented or cured. Diet-derived long-chain polyunsaturated fatty acids (PUFAs) are incorporated in brain lipids and modulate oxidative and inflammatory processes and could thus affect ALS risk and progression.To examine the association between ω-6 and ω-3 PUFA consumption and ALS risk.Longitudinal analyses based on 1,002,082 participants (479,114 women and 522,968 men) in 5 prospective cohorts: the National Institutes of Health-AARP Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Health Professionals Follow-up Study, the Multiethnic Cohort Study, and the Nurses' Health Study. Diet was assessed via food frequency questionnaire developed or modified for each cohort. Participants were categorized into cohort-specific quintiles of intake of energy-adjusted dietary variables.Cohort-specific multivariable-adjusted risk ratios (RRs) of ALS incidence or death estimated by Cox proportional hazards regression and pooled using random-effects methods.A total of 995 ALS cases were documented during the follow-up. A greater ω-3 PUFA intake was associated with a reduced risk for ALS. The pooled, multivariable-adjusted RR for the highest to the lowest quintile was 0.66 (95% CI, 0.53-0.81; P < .001 for trend). Consumption of both α-linolenic acid (RR, 0.73; 95% CI, 0.59-0.89; P = .003 for trend) and marine ω-3 PUFAs (RR, 0.84; 95% CI, 0.65-1.08; P = .03 for trend) contributed to this inverse association. Intakes of ω-6 PUFA were not associated with ALS risk.Consumption of foods high in ω-3 PUFAs may help prevent or delay the onset of ALS.
Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs
Authors: J Haapala, J P A Arokoski, S Rönkkö, U Ågren, V-M Kosma, L S Lohmander, M Tammi, H J Helminen, I Kiviranta
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To monitor the concentration of markers of cartilage and synovium metabolism in the knee (stifle) joint synovial fluid of young beagles subjected to immobilisation and subsequent remobilisation. <h3>METHODS</h3> The right hind limb of 17 dogs was immobilised in flexion for 11 weeks. Simultaneously, the contralateral left knee was exposed to increased weight bearing. The remobilisation period lasted 50 weeks. Litter mates served as controls. The concentration in joint lavage fluid of interleukin 1α (IL1α) was measured by immunoassay, the activity of phospholipase A<sub>2</sub> (PLA<sub>2</sub>) was determined by an extraction method, chondroitin sulphate (CS) concentration by precipitation with Alcian blue, hyaluronan (HA) by an ELISA-like assay using biotinylated HA-binding complexes, matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinases 1 (TIMP-1) by sandwich ELISA, and synovitis was scored by light microscopy. <h3>RESULTS</h3> Synovitis or effusion was absent in all experimental and control groups. Immobilisation decreased the joint lavage fluid levels of IL1α (p&lt;0.05), TIMP (p&lt; 0.05), and the concentration of CS down to 38% (p&lt;0.05) in comparison with untreated litter mates with normal weight bearing. Immobilisation did not affect the activity of PLA<sub>2</sub>, or the concentration of MMP-3 or HA in synovial fluid. Joint remobilisation restored the decreased concentrations of markers to control levels. Increased weight bearing did not change the concentrations of markers in comparison with the control joints with normal weight bearing. <h3>CONCLUSIONS</h3> 11 weeks9 joint immobilisation decreased the concentration of markers of cartilage and synovium metabolism in the synovial fluid, and remobilisation restored the concentrations to control levels. The changes in joint metabolism induced by immobilisation, as reflected by the markers, are thus different from those found in osteoarthritis, where increased levels of these markers are associated with enhanced degradation and synthesis. These findings suggest that the change induced in joint metabolism by immobilisation is reversible in its early stages.
Liver disease in the UK: Startling findings &amp; urgent need for action
Authors: Roger Williams
Journal: Journal of Hepatology (2015)

The report of the Lancet Commission [1] published in the Lancet on November 27th 2014, makes for interesting reading. It was entitled ‘‘Addressing the Crisis of Liver Disease in the UK: A blueprint for obtaining excellence in healthcare for liver disease and reducing premature mortality from the major lifestyle issues of excess alcohol consumption, obesity and viral hepatitis’’. The findings in the UK are also relevant to current concerns over liver disease in Europe. An important milestone at the European policy level is the launch in the European Parliament [2] last month, by the European Association for the Study of the Liver (EASL), of the ‘Research Roadmap for Liver Disease’ (HEPAMAP). In 2013, 29 million people in the EU were documented as suffering from a chronic liver condition and HEPAMAP identifies opportunities to significantly reduce liver mortality and decrease the burden of liver conditions in the EU by the end of 2020, with particular emphasis on tackling alcoholand obesity-related liver conditions with evidence-based policy measures. The recommendations of the Lancet report, with nearly two hundred references, are based on the work of some fifty experts from a wide variety of disciplines. They reviewed in detail epidemiological and clinical data, including an important report from the National Confidential Enquiry into Patient Outcomes and Death (NCEPOD) [3], of an audit carried out in hospitals around the country on the care of adult liver patients admitted to hospital. Major deficiencies in the available facilities and lack of expertise in those caring for the patients were documented. Only 2.9% of the patients had been seen by a consultant Hepatologist on arrival. Care was judged to have been good in less than half the cases and deaths were considered avoidable in over 10%. The statistics for the UK are horrifying. Liver disease stands out as the one glaring exception to the vast improvement over the past 30 years in health and life expectancy for chronic disorders such as strokes, heart disease and many cancers. Mortality
Human hematopoietic cells and thymic epithelial cells induce tolerance via different mechanisms in the SCID-hu mouse thymus.
Authors: B A Vandekerckhove, R Namikawa, R Bacchetta, M G Roncarolo
Journal: The Journal of Experimental Medicine (1992)

To study the role of thymic education on the development of the human T cell repertoire, SCID-hu mice were constructed with fetal liver and fetal thymus obtained from the same or two different donors. These animals were studied between 7 and 12 mo after transplantation, at which times all thymocytes and peripheral T cells were derived from stem cells of the fetal liver graft. Immunohistology of the thymus grafts demonstrated that thymic epithelial cells were of fetal thymus donor (FTD) origin. Dendritic cells and macrophages of fetal liver donor (FLD) origin were abundantly present in the medullary and cortico-medullary areas. Thymocytes of SCID-hu mice transplanted with liver and thymus of two different donors (FLDA/FTDB animals) were nonresponsive to Epstein-Barr virus-transformed B cell lines (B-LCL) established from both the FLDA and FTDB, but proliferated vigorously when stimulated with third-party allogeneic B-LCL. Mixing experiments showed that the nonresponsiveness to FTDB was not due to suppression. Limiting dilution analysis revealed that T cells reacting with the human histocompatibility leukocyte antigens (HLA) of the FLD were undetectable in the CD8+ T cell population and barely measurable in the CD4+ subset. On the other hand, CD4+ and CD8+ T cells reactive to the HLA antigens of the FTD were readily detectable. These results indicate that FLD-reactive cells were clonally deleted, whereas FTD-reactive cells were not. However, the frequencies of FTD-reactive T cells were consistently twofold lower than those of T cells specific for any third-party B-LCL. In addition, the cytotoxic activity and interleukin 2 production by FTD-specific T cells were lower compared with that of third-party-reactive T cell clones, suggesting that FTD-specific cells are anergic. These data demonstrate that T cells become tolerant to autologous and allogeneic HLA antigens expressed in the thymus via two different mechanisms: hematopoietic cells present in the thymus induce tolerance to "self"-antigens by clonal deletion, whereas thymic epithelial cells induce tolerance by clonal energy and possibly deletion of high affinity clones.