tbuckley/cabot-search huggingface dataset:
Safety and efficacy of ipilimumab to treat advanced melanoma in the setting of liver transplantation
Authors: Rita E Morales, Alexander N Shoushtari, Michelle M Walsh, Priya Grewal, Evan J Lipson, Richard D Carvajal
Journal: Journal for ImmunoTherapy of Cancer (2015)

Ipilimumab is a first-in-class immunological checkpoint blockade agent and monoclonal antibody against Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) that has demonstrated survival benefit and durable responses in patients with metastatic melanoma. To date, solid organ transplant recipients have been excluded from clinical trials with cancer immunotherapies on the basis of their concurrent treatment with immunosuppressive agents. We present the first case to our knowledge of a patient with advanced cutaneous melanoma receiving ipilimumab status post orthotopic liver transplantation with a partial response. Transaminitis was observed 4 months after administration of ipilimumab that resolved with close observation. No evidence of graft rejection has been observed to date. This case advocates for further investigation of the safety and efficacy of cancer immunotherapies in solid organ transplant recipients.
Left Ventricular Remodeling in Elite Athletes
Authors: Kofo O. Ogunyankin
Journal: Circulation (2002)

To the Editor:Pellicchia et al 1 should be congratulated for their unique database and their recent paper on ventricular remodeling after cessation of competitive sports in elite athletes.Their conclusion that ventricular cavity size and wall thickness decreased in all athletes after detraining is consistent with reports in previous longitudinal studies. 2,3However, their observation that ventricular size does not completely normalize should be further qualified by data that were not clearly reported in the article.The spread of 1 to 13 years for the interval between cessation of exercise and the reported follow-up measurement may be the greatest confounder of these results.Given that short-term training followed by cessation is associated with normalization of ventricular dimensions, 2,3 it is reasonable to expect that long-term cumulative changes may regress more slowly.Could it be that the athletes closest to detraining were the ones with persistent cavity enlargement?Furthermore, the duration of performance at elite levels prior to commencement of detraining cannot be gleaned from the report.Athletes with several years of training could be expected to have a bigger left ventricular cavity than those with less training, and therefore require a longer detraining observation period before cavity size normalizes.Was the observed incomplete normalization of volume seen predominantly in those with longer duration of elite performance?Another confounder is the persistence of light recreational activities in the majority (62.5%) of the former athletes.Hickson et al 4 showed that continued training at a reduced level could prevent regression of the training-induced morphometric changes in former athletes.Although this study reports no difference in the mean left ventricular cavity size between completely deconditioned athletes and those with persistent exercise, a difference cannot be excluded unless the dimensions are indexed to both the dimensions during peak performance and the relative reduction in peak training represented by detraining activity.This unique database should clarify these important issues.
Abstract 15453: CaMKII Plays a Critical Role in Pressure Overload-Induced Left Ventricular Hypertrophy by Modulating Foxp1 Expression
Authors: Lin Zhao, Guangming Cheng, Runming Jin, Lei Chen, Anweshan Samanta, Magdy Girgis, Harold K Elias, Arash Davani, Kashyap Choksi, Robert Vincent, Yanjuan Yang, Jeryl Hauptman, Buddhadeb Dawn
Journal: Circulation (2014)

Introduction: The necessity of IL-6 signaling in pressure overload-induced left ventricular hypertrophy remains controversial. Whether Calcium/calmodulin-dependent kinase II (CaMKII) participates in IL-6-induced and pressure overload-induced hypertrophic signaling remains unknown. Hypothesis: CaMKII acts as a nodal point for integrating IL-6 signaling in pressure overload induced hypertrophic molecular pathways. Methods and Results: In vitro, exposure to IL-6 for 24 h induced hypertrophy in H9c2 cells. This hypertrophic response was associated with robust increase in phospho-CaMKII levels in IL-6-treated cells, and accompanied by increase in myocyte hypertrophy markers. Interestingly, Mef2a levels also increased, and this was associated with reduced Foxp1 expression, which has Mef2a specific binding site at CTAAAAATAG (-401 ~ -391) in Foxp1 promoter sequence. These effects were inhibited by selective CaMKII inhibitor KN-62. Next, we performed transverse aortic constriction (TAC) in IL-6-/- mice and wild-type (WT) C57BL/6J mice to induce hypertrophy. After 6 wks, TAC-induced hypertrophy was significantly attenuated in IL-6-/- mice compared with WT mice, documented by necropsy findings, echocardiography, and LV morphometry. Phospho-CaMKII levels increased significantly in control mouse hearts at 2 wks after TAC, while this increase was significantly blunted in IL-6-/- hearts (Figure). Moreover, and consistent with attenuated CaMKII activity, the expression of Mef2a was lower and expression of Foxp1 was higher in IL-6-/- hearts after TAC compared with controls. Conclusions: We identify a novel signaling module whereby regulation of Foxp1 by CaMKII plays a critical role in pressure overload-induced and IL-6-mediated cardiac hypertrophy. These molecular insights may lead to formulation of novel therapeutic agents for LV hypertrophy and dysfunction.
Regulation of the Fanconi Anemia/BRCA pathway
Authors: Alan D. D’Andrea
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

SY28-2 

Fanconi Anemia (FA) is an autosomal recessive cancer susceptibility syndrome characterized by cellular hypersensitivity to DNA crosslinking agents. There are eleven complementation groups of FA (A, B, C, D1, D2, E, F, G, L, I, J), and nine FA genes have been cloned. The FANCD2 gene is identical to the BRCA2 gene. The nine cloned FA proteins cooperate in a novel cellular DNA damage response pathway (the FA/BRCA pathway). This pathway is activated during the S phase of the cell cycle. Specifically, in S phase, when a replication fork encounters an interstrand crosslink, the FA complex (consisting of FA proteins A, B, C, E, F, G, L) becomes an active monoubiquitin ligase. This complex monoubiquitinates the downstream FANCD2 protein, leading to its targeting to DNA repair foci containing FANCD1/BRCA2. Disruption of this pathway leads to a failure to repair DNA crosslinks. We have recently identified other regulatory proteins which control the cell cycle specific activation of the FA/BRCA pathway. The ATR kinase, for example, is required for the S phase specific phosphorylation of FANCD2 (Andreassen PR, D’Andrea AD, Taniguchi T. ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes & Development 18: 1958-1963, 2004). In addition, we have identified a novel deubiquitinating enzyme (USP1) which cleaves FANCD2-Ub (Nijman et al, 2004, submitted). FANCD2-Ub is localized to the chromatin, has DNA binding activity, and appears to be required to prevent collapse of the replication fork. USP1 cleavage of FANCD2-Ub at the end of S phase, results in exit of FANCD2 from the chromatin fraction and a completion of DNA replication. While the precise role of FANCD2 monoubiquitination during S phase is unknown, it may function as a mechanism to (a) turn on homologous recombination (HR) repair and/or (b) switch on DNA translesion synthesis (TLS) polymerases. The precise role of the USP1 protease in regulation the of the FA/BRCA pathway will be discussed.
Protective eyewear for young athletes
Authors: J CAPAOFILIPE
Journal: Ophthalmology (2005)

I read with great interest the Joint Policy Statement about protective eyewear for young athletes.1 The publication considers mainly racket sports, baseball, basketball, women's lacrosse, and field hockey. The need for protective eyewear in soccer was given far less attention than for these selected sports.2 Our study confirmed that the soccer ball causes eye injury by protruding into the orbit. In addition, we concluded that protectors that pass American Society for Testing and Materials Standard F803 and have polycarbonate lenses would prevent orbital intrusion.
Abstract 17352: Differences in Clinical Characteristics, Risk Factors, Rate of Recurrence and 1-year Outcome Between Acute Heart Failure Patients With Stroke or TIA and Those Without This Co-morbidity. Results From the Gulf aCute heArt failuRe rEgistry (gulf Care)
Authors: Mohammed A Al Hashemi, Kadhim Sulaiman, Jassim Al-Suwaidi, Khalid F AlHabib, Husam AlFaleh, Abdelfatah Elasfar, Ahmed Al-Motarreb, Prashanth Panduranga, Nidal Asaad Nidal Asaad, Wael Almahmeed, Alawi Alsheikh-Ali, Nooshin Bazargani, Mustafa Ridha, Bassam Bulbanat, Mohammed Al-Jarallah, Haitham Amin, Christian Bollensdorff, Magdi Yacoub
Journal: Circulation (2014)

Background: Chronic heart failure (CHF) is a known risk for stroke and morbidities and mortalities are known to be higher in CHF patients compared to stroke patients without CHF we here study the prevalence and the clinical significance in a group of patient with stroke or transient ischemic attack (TIA) who were admitted to hospital with acute heart failure (AHF) compared to those without stroke and are admitted with acute heart failure Methods: Data were derived from a prospective, multicenter, multinational study of 5005 patients hospitalized with AHF from February 2013 to November 2012. Data were analyzed according to the presence or absence of Stroke or bronchial TIA. Demographic, management, in-hospital and 1-year outcomes were compared Results: Stroke patients were likely to have a decompensation of chronic failure rather than De-Novo AHF when compared to those without Stroke/TIA (see table). Stroke patients were older; more likely to be female, have history of DM, HTN, dyslipidemia and CKD. Stroke patients were likely to have Atrial fibrillation, PVD, systolic LV dysfunction as well as CAD when compared to those without Stroke, they were also more likely receive NIV, IV inotropes and likely to have had cardiac PCI prior to this admission with AHF. Stroke patients had higher recurrence of stroke and one-year mortality rates. Conclusion: Patients who presented with AHF and history of stroke/TIA were having different clinical characteristics as well as comorbidities as compared to those without Stroke, with worse in-hospital and one-year outcome. The current study underlies the need to aggressively manage these high-risk patients.
Side effects of α interferon in chronic hepatitis C
Authors: G Dusheiko
Journal: Hepatology (1997)

Alpha interferons have been used widely to treat chronic hepatitis C virus infection. These include recombinant interferons, purified natural leukocyte, and lymphoblastoid interferons. Alpha interferon is administered by subcutaneous or intramuscular injection either daily or three times weekly for a period of 6 to as long as 24 months. A wide array of adverse effects of α interferon have been described. Several side effects such as fever, headache fatigue, arthralgias, and myalgias are common, especially with the initial injections. These early side effects of interferon are predictable and are encountered in the majority of patients. These may not require dose modification, but can be problematic for a significant proportion of patients. Other adverse events effects may require dose modification or even discontinuation of therapy in 2% to 10% of patients. Neuropsychiatric side effects such as depression and irritability can be most troublesome; their mechanisms are not well understood. Granulocytes, platelets, and red blood cell counts decrease during treatment, but the decreases are usually mild, although they can be dose limiting if cell counts are low initially. Interferon has important immunomodulatory properties, and treatment can induce autoimmune phenomena, the most frequent being autoimmune thyroiditis with either hypothyroidism or hyperthyroidism, especially in predisposed patients. Other autoimmune disease can be aggravated by interferon therapy. Severe and even life- threatening side effects of interferon occur in 0.1% to 1% of patients; these include thyroid, visual, auditory, renal, and cardiac impairment, and pulmonary interstitial fibrosis. Some of these side effects may be irreversible. Higher doses of interferon (above 5 million units three times weekly) cause higher rates of adverse events than standard doses. Contraindications to α interferon have been recognized.
Press: The BMJ, spin, and the stockmarket
Authors: R. Smith
Journal: BMJ (2000)

One of the many anxieties of medical editors is that we have little measurable impact on anything. Systematic reviews have shown that written information is ineffective in changing doctors' practice. “All we do,” claimed my predecessor as editor, “is take in other people's washing.” I thus read with mixed feelings the Independent headline “BMJ admits ‘lapses’ after article wiped £30m off Scotia shares” (10 June). Could a BMJ mistake really have such dramatic consequences? Unsurprisingly, the story is much more complex than the headline suggests and provides yet another example of the story being spun to meet a commercial agenda.

The story begins with us publishing a drug point that suggested that a new anticancer drug in phase I trials might cause skin burns in 40% of patients (6 May, p 1245). The drug—temoporfin (Foscan)—is a photosensitiser that accumulates in malignant tissues and then is activated by light to destroy the tissue. We published the drug point to alert readers to this possible side effect. Medical journals face a difficult problem with such reports, which are usually based on a single case or a small series of patients. We know that we don't get it right every time. Sometimes we publish reports of effects that turn out …
Brief Report: Cryopyrin‐Associated Periodic Syndrome Caused by a Myeloid‐Restricted Somatic <i>NLRP3</i> Mutation
Authors: Qing Zhou, Ivona Aksentijevich, Geryl M. Wood, Avram D. Walts, Patrycja Hoffmann, Elaine F. Remmers, Daniel L. Kastner, Amanda K. Ombrello
Journal: Arthritis & Rheumatology (2015)

To identify the cause of disease in an adult patient presenting with recent-onset fevers, chills, urticaria, fatigue, and profound myalgia, who was found to be negative for cryopyrin-associated periodic syndrome (CAPS) NLRP3 mutations by conventional Sanger DNA sequencing.
Abstract 13404: Serum Anti-Intercalated Disk Autoantibodies in Arrhythmogenic Right Ventricular Cardiomyopathy are Autoimmune Markers Associated with Pathogenic Desmosomal Mutations
Authors: Alida L Caforio, Elisabetta Zachara, Federica Re, Pasquale Baratta, Francesco Bagato, Gaetano Thiene, Sabino Iliceto, Petros Syrris, William J McKenna
Journal: Circulation (2011)

Objective: Serum anti-heart autoantibodies (AHA) and anti-intercalated disk autoantibodies (AIDA) are organ and disease-specific autoimmune markers in myocarditis, dilated cardiomyopathy and their ...
3‐Nitrotyrosine, a marker of nitrosative stress, is increased in breath condensate of allergic asthmatic children
Authors: E. Baraldi, G. Giordano, M. F. Pasquale, S. Carraro, A. Mardegan, G. Bonetto, C. Bastardo, F. Zacchello, S. Zanconato
Journal: Allergy (2005)

Background: Asthmatic patients have high exhaled nitric oxide (NO) levels. NO‐mediated inflammatory actions are mainly due to NO conversion into reactive nitrogen species, which can lead to nitrotyrosine formation. The aim of this study was to assess 3‐nitrotyrosine (3‐NT) levels in exhaled breath condensate (EBC) of asthmatic and healthy children and to investigate whether there is any relationship with exhaled NO (FE NO ) and lung function. Methods: The study included 20 asthmatic children (10 steroid‐naive with intermittent asthma, 10 steroid‐treated with unstable persistent asthma) and 18 healthy controls. They underwent FE NO measurement, EBC collection and spirometry. 3‐NT was measured by a new liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method in isotopic dilution. Results: The median EBC concentration of 3‐NT (expressed as nitrotyrosine/tyrosine ratio × 100) in asthmatic children was fivefold higher than in healthy subjects [0.23% (0.12–0.32) vs 0.04% (0.02–0.06), P &lt; 0.001] with no difference between steroid‐naive and unstable steroid‐treated asthmatic patients. FE NO levels were higher in asthmatic [44.6 ppb (36.0–66.0)] than in healthy children [7.5 ppb (6.0–8.8), P &lt; 0.001]. No correlation was found among 3‐NT, FE NO and lung function parameters. Conclusion: Nitrotyrosine is high in EBC of asthmatic children and could be considered as a noninvasive marker of nitrosative events in the airways.
Racism and health
Authors: P. S Gill
Journal: BMJ (2003)

Editor—As McKenzie highlights in his editorial, the emphasis to date has been on the role of racism in recruitment and career development.1 This must continue despite initiatives and legislation such as the recent Race Relations Amendment Act, as racism still exists in the NHS.2 We need to continue to challenge racism not only from our colleagues but also from our patients—zero tolerance is needed.3

The importance of racism on health and health care will not diminish owing to increasing migration to the United Kingdom particularly from east European countries. The often hostile reception of the public, media, and some politicians reinforces the negative attitudes that prevail,4 and these may manifest through acute and chronic stress to the detriment of the individual. Research on evaluating the mechanism for racism and health outcomes is in early infancy; most studies are being conducted in the United States. We agree with McKenzie that further funding is needed in this area.

The biological models alluded to seem plausible, but before investigating these further substantial research needs to be done first to define, measure, and validate “racism” as an epidemiological variable. Then we need studies to disentangle the effect of racism on health. Urgency and opportunity exist to initiate a national ethnic cohort study within the planned UK Biobank study (www.ukbiobank.ac.uk) to include examination of the effect of racism on health outcomes.
Mechanisms and Management of Retinopathy of Prematurity
Authors: Rajesh C. Rao, Brian J. Dlouhy
Journal: New England Journal of Medicine (2013)

Retinopathy of prematurity is a vision-threatening disease associated with abnormal retinal vascular development that occurs only in premature infants. 1 Low birth weight and prematurity are strongly associated with an increased risk of the disease. 2 In the Early Treatment for Retinopathy of Prematurity study, the disorder developed in 68% of premature infants born in the United States and weighing less than 1251 g; among infants with the disorder, severe retinopathy of prematurity developed in almost 37%. 1 The incidence of premature births is increasing throughout the world, and with it, retinopathy of prematurity is now appearing in countries with the technology to save preterm infants.Thus, retinopathy of prematurity has become a leading cause of childhood blindness worldwide.The management of retinopathy of prematurity is evolving.Screening and treatment interventions include frequent retinal examinations of at-risk preterm infants, laser treatment of the peripheral avascular retina in eyes with severe retinopathy of prematurity, and visual rehabilitation (Table 1 and Fig. 1). 1,3In this article, we review our changing understanding of retinopathy of prematurity, particularly its relation to oxygen use 4-7 (Table 2 8 -12 ), and describe current, new, and potential therapies based on mechanistic studies in models relevant to oxygen stresses in preterm infants. PATHOGENESISDuring the 70 years since retinopathy of prematurity was initially described by Terry, who used the term "retrolental fibroplasia," 4 our perspective on the condition has changed.We now think that the initial 1942 description may have represented stage 5 retinopathy of prematurity, the most advanced stage of the disease, characterized by total retinal detachment.In addition, the early studies by Michaelson, 5 Ashton et al., 6 and Patz et al.,7 which examined the effects of high oxygen levels in newborn animal models in which the retinas normally vascularize postnatally (unlike human infants, in whom the retina is vascularized at term but not in preterm births), must now be reconsidered in light of advancements in neonatal care.Although these early investigators exposed animals to a high-oxygen milieu similar to that used in the treatment of preterm infants at the time, they did not consider the fact that the newborn animals they studied had healthy lung function.In addition, the oxygen levels used then differ considerably from those currently used in preterm infants.Ashton and colleagues reported that 70% to 80% inspired oxygen delivered continuously for at least 4 days in healthy kittens caused "vaso-obliteration" of the newly formed capillaries 6 ; when the animals were returned to ambient air, a "vasoproliferative"
Lysis of Homologous Cells by Sensitized Lymphocytes in Tissue Culture&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Werner Rosenau, Henry D. Moon
Journal: JNCI Journal of the National Cancer Institute (1961)

Journal Article Lysis of Homologous Cells by Sensitized Lymphocytes in Tissue Culture Get access Werner Rosenau, M.D., Werner Rosenau, M.D. Department of Pathology and Cancer Research Institute, University of California, San Francisco Medical Center, San Francisco, California Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry D. Moon, M.D. Henry D. Moon, M.D. Department of Pathology and Cancer Research Institute, University of California, San Francisco Medical Center, San Francisco, California Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 27, Issue 2, August 1961, Pages 471–483, https://doi.org/10.1093/jnci/27.2.471 Published: 01 August 1961 Article history Received: 31 March 1961 Published: 01 August 1961
No-Discount Cards?
Authors: Brian Vastag
Journal: JAMA (2004)

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