tbuckley/cabot-search huggingface dataset:
Abstract 4406: CARD11 is critical for in vitro and in vivo growth of ABC-DLBCL cells.
Authors: Joshua C. Murtie, Julia Zhu, Hongyun Wang, Beatriz Ospina, May Cindhuchao, Dietmar Hoffman, Rita Greco, Marion Dorsch, Francisco Adrian
Journal: Cancer Research (2013)

Abstract Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma and can be divided into three distinct subtypes. The activated B cell-like (ABC) subtype is the most aggressive and is characterized by constitutive activation of the NF-κB pathway. CARD11 is a scaffolding protein and plays a critical role in the NF-κB pathway by coordinating IκB kinase activity and downstream pathway activation. Previous studies have revealed that ABC-DLBCL cell lines are dependent on the NF-κB pathway (Davis et al., 2001). Furthermore, activating mutations in CARD11 occur in approximately 10% of ABC-DLBCL patient tumors and result in constitutive activation of the NF-κB pathway (Lenz et al., 2008). Using a combination of genetic and pharmacological tools we have further demonstrated that CARD11 is a critical node of the NF-κB pathway essential for B cell lymphoma growth in vitro and in vivo. Using a variety of pharmacological inhibitors, we demonstrate that anti-proliferative activity of each compound corresponds with its ability to inhibit the NF-κB pathway in an ABC-DLBCL cell line, TMD-8, engineered to express luciferase under the control of an NF-κB responsive promoter. Next, using doxycycline-inducible shRNAs targeting CARD11, we confirm the dependency of TMD-8 cells on CARD11 in vitro. The effects of CARD11 knockdown can be rescued by reactivation of the NF-κB pathway downstream of CARD11 by addition of TNF-α to a TMD-8 line engineered to express the TNF receptor. After validation of CARD11 dependency in vitro, we generated tumor xenografts using TMD-8 cells transduced with doxycycline-inducible shRNAs against CARD11. Upon treatment with doxycycline, TMD-8 tumor xenografts showed stasis or regression as a result of CARD11 knockdown. This inhibition of tumor growth also corresponded with significant down-regulation of the NF-kB responsive genes IL-6 and IL-10. Together these data demonstrate that ABC-DLBCL cells and tumors require CARD11 for growth in an NF-kB dependent manner. Citation Format: Joshua C. Murtie, Julia Zhu, Hongyun Wang, Beatriz Ospina, May Cindhuchao, Dietmar Hoffman, Rita Greco, Marion Dorsch, Francisco Adrian. CARD11 is critical for in vitro and in vivo growth of ABC-DLBCL cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4406. doi:10.1158/1538-7445.AM2013-4406
The Multiple Pregnancy
Authors: Emanuel A. Friedman
Journal: JAMA (1965)

Perinatal mortality is very high in multiple pregnancy, and there are correspondingly greater losses in triplet and quadruplet pregnancies than in twins. It has been shown that even under the most favorable circumstances, fetal loss is still two or three times greater for multiple than for single births. Antepartum and intrapartum complications are quite common as immediate causes of death, but the greatest single threat to life appears to be prematurity. More than half the babies born in multiple pregnancies are premature by weight and are, therefore, subjected to the associated risks. It has been said that the judgment and technical skill of the obstetrician are particularly important in multiple pregnancy, and this undoubtedly applies especially for the unfortunate infants which follow the eldest in birth order. The excessive mortality of second twins over that of the first born has been adequately demonstrated.<sup>1</sup> With reference to the matter of
Melusin protects from cardiac rupture and improves functional remodelling after myocardial infarction
Authors: Bernhard Unsöld, Axel Kaul, Mauro Sbroggiò, Carola Schubert, Vera Regitz-Zagrosek, Mara Brancaccio, Federico Damilano, Emilio Hirsch, Marc Van Bilsen, Chantal Munts, Karin Sipido, Virginie Bito, Elke Detre, Nana Maria Wagner, Katrin Schäfer, Tim Seidler, Johannes Vogt, Stefan Neef, Annalen Bleckmann, Lars S. Maier, Jean Luc Balligand, Caroline Bouzin, Renée Ventura-Clapier, Anne Garnier, Thomas Eschenhagen, Ali El-Armouche, Ralph Knöll, Guido Tarone, Gerd Hasenfuß
Journal: Cardiovascular Research (2013)

Abstract Aims Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach. Methods and results Mice overexpressing melusin in the heart (TG) and wild-type controls (WT) were subjected to permanent LAD ligation and both the acute response (Day 3) and subsequent remodelling (2 weeks) were examined. Mortality in wild-type mice was significant between Days 3 and 7, primarily due to cardiac rupture, but melusin's overexpression strongly reduced mortality (43.2% in wild-type vs. 27.3% in melusin-TG, P = 0.005). At Day 3 after MI, a time point preceding the mortality peak, TG hearts had increased heat shock protein 70 expression, increased ERK1/2 signalling, reduced cardiomyocyte hyper-contractility and inflammatory cell infiltrates, and increased matricellular protein expression in the infarcted area. At 2 weeks after MI, melusin overexpression conferred a favourable adaptive remodelling characterized by reduced left ventricle dilatation and better preserved contractility in the presence of a comparable degree of hypertrophy. Adaptive remodelling in melusin TG mice was characterized by reduced apoptosis and fibrosis as well as increased cardiomyocyte contractility. Conclusions Consistent with its function as a chaperone protein, melusin overexpression exerts a dual protective action following MI reducing an array of maladaptive processes. In the early phase after MI, reduced inflammation and myocyte remodelling protect against cardiac rupture. Chronically, reduced myocyte loss and matrix remodelling, with preserved myocyte contractility, confer adaptive LV remodelling.
Methotrexate-induced exacerbation of urticarial vasculitis: an unusual adverse reaction
Authors: A. Borcea, M.W. Greaves
Journal: British Journal of Dermatology (2000)

Journal Article Methotrexate‐induced exacerbation of urticarial vasculitis: an unusual adverse reaction Get access A. Borcea, A. Borcea Professorial Unit, St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Correspondence: Professor M.W.Greaves Search for other works by this author on: Oxford Academic Google Scholar M.W. Greaves M.W. Greaves Professorial Unit, St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Correspondence: Professor M.W.Greaves Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 1, 1 July 2000, Pages 203–204, https://doi.org/10.1046/j.1365-2133.2000.03624.x Published: 01 July 2000
Respiratory Health in a Globalizing World
Authors: SOLOMON R. BENATAR
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

to design new, more specific therapeutic agents. New functional imaging diagnostic techniques, less invasive surgical methods, and specifically designed target drugs could contribute to more efficient treatment of many disorders. Advances in information technology could enable home monitoring of patients with asthma and chronic obstructive pulmonary disease (COPD) and further empower patients, especially those who can afford it, to care for themselves. Distance diagnosis and teaching (e.g., through Internet transmission of radiological and video images) and more widespread access to electronic literature sources could facilitate the spread of knowledge and expertise. While it is the hope of many that such advances will improve respiratory health globally, the risk that such advances will be available only to those with resources should not be underestimated ( see below ).
TREATMENT OF DISSEMINATED SCLEROSIS BY LIVER
Authors: A. Goodall, J. K. Slater
Journal: BMJ (1931)

they are based on the 250 consecutive cases of the last eighteen months:1.A perfcct and safe surgical anaesthesia is obtainable in about 8X to 98 per cent. of operations in the abdomen and legs.The lower figure occurs with the higher levels of anaesthesia.2. Anaesthesia is not derived from the introduction of narcotics into, and the altered chemistry of, the blood, but merely by the transitory interruption of conductivity in the nerves of the lower part of the body.3. The apparatus is simple and can be carried in the pocket.4. The dose, except in childhood, is standardized, and varies only with the level of anaesthesia desired.This makes for ease and safety, and is an advantage over other anaesthetics.5. The metabolic processes of the body are reduced during the operation for one to one and a half hours, thus conserving energy.With recovery from paralysis, the rested heart, vessels, muscles, and glandular organs are founid working with notable buoyaicy and renewed strength.6.The patient's muscles relax completely, as if aiding, rathler than resisting, the surgeon's mancuvres.Un- disturbed tranquillity reigns in the field of operation, and smooth, easy working results, which saves the strength of both patient and surgeon, and minimizes the trauma to tissues.7. The paralysis of inhibitory sympathetic nerves to the intestine assists by encouraging peristalsis and bowel clearance in cases of intestinal obstruction; indeed, spinal aniaesthesia is used as a treatment for paralytic ileus.8. The patient is returned to the ward conscious and quiet.No recovery restlessness ensues.So are spared his stitched and wounded tissues, his recuperative powers, and the time and energy of the nursing staff.Food is taken early, and the body tissues are ready to digest and to use it. 9. Infants, children, and adults, in many cases, prefer it.This paper would not be complete without grateful acknowledgejnent to -all the kind and patient colleagues who have helped.me through the difficulties of the early stages of this research.
ACAT Inhibition and Progression of Carotid Atherosclerosis in Patients With Familial Hypercholesterolemia
Authors: Marijn C. Meuwese, Eric de Groot, Raphaël Duivenvoorden, Mieke D. Trip, Leiv Ose, Frans J. Maritz, Dick C. G. Basart, John J. P. Kastelein, Rafik Habib, Michael H. Davidson, Aeilko H. Zwinderman, Lee R. Schwocho, Evan A. Stein, for the CAPTIVATE Investigators
Journal: JAMA (2009)

Inhibition of acyl coenzyme A:cholesterol acyltransferase (ACAT), an intracellular enzyme involved in cholesterol accumulation, with pactimibe was developed to assist in the prevention of cardiovascular disease.To evaluate the efficacy and safety of pactimibe in inhibition of atherosclerosis.A prospective, randomized, stratified, double-blind, placebo-controlled study (Carotid Atherosclerosis Progression Trial Investigating Vascular ACAT Inhibition Treatment Effects [CAPTIVATE]) of 892 patients heterozygous for familial hypercholesterolemia conducted at 40 lipid clinics in the United States, Canada, Europe, South Africa, and Israel between February 1, 2004, and December 31, 2005. Study was terminated on October 26, 2005.Participants received either 100 mg/d of pactimibe (n = 443) or matching placebo (n = 438), in addition to standard lipid-lowering therapy.Carotid atherosclerosis, assessed by ultrasound carotid intima-media thickness (CIMT), at baseline, 12, 18, and 24 months. Maximum CIMT was the primary end point and mean CIMT the secondary end point.Because pactimibe failed to show efficacy in the intravascular coronary ultrasound ACTIVATE study, the CAPTIVATE study was terminated prematurely after a follow-up of 15 months. After 6 months of treatment with pactimibe, low-density lipoprotein cholesterol increased by 7.3% (SD, 23%) compared with 1.4% (SD, 28%) in the placebo group (P = .001). The carotid ultrasonographic scans of the 716 patients with at least 2 scans and obtained at least 40 weeks apart were analyzed. Maximum CIMT measurements did not show a pactimibe treatment effect (difference, 0.004 mm; 95% confidence interval [CI], -0.023 to 0.015 mm; P = .64); however, the less variable mean CIMT measurement revealed an increase of 0.014 mm (95% CI, -0.027 to 0.000 mm; P = .04) in patients administered pactimibe vs placebo. Major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) occurred more often in patients administered pactimibe vs placebo (10/443 [2.3%] vs 1/438 [0.2%]; P = .01).In patients with familial hypercholesterolemia, pactimibe had no effect on atherosclerosis as assessed by changes in maximum CIMT compared with placebo but was associated with an increase in mean CIMT as well as increased incidence of major cardiovascular events.clinicaltrials.gov Identifier: NCT00151788.
A Prepaid Medical Plan
Authors: Walter M. Bortz
Journal: JAMA (1977)

A model experience of a prepaid medical plan for a group of people is analyzed. No-barrier cost and physician access lead to altered use characteristics. Among these are increased physician, nurse, and nursing home use, and decreased hospital use. The overall cost is increased. Any comprehensive health-care plan that would propose comprehensive first-dollar coverage would likely encounter similar use characteristics.
Decline in autopsy rate
Authors: R. Dyson
Journal: Journal of the Royal Society of Medicine (2002)

Organ retention issues have certainly played an important part in the fall in autopsy rate reported by Dr Carr and his colleagues (July 2002 JRSM1). I was disappointed, however, to see no reference to the growing shortage of histopathologists within the NHS and the effect this has undoubtedly had upon postoperative autopsy requesting. The report also expresses concern that only 70% of autopsy reports were rated satisfactory or better. It may be that the pressure of work upon existing NHS histopathologists has contributed to this result as well. Finally, an issue of more general concern is whether autopsy requesting is being tightened, following the organ retention debate, to minimize the true extent of the supply/demand gap in histopathology. Some would call this judicious demand management in a time of labour scarcity; others would focus more upon the clinical risks and disadvantages demonstrated by Carr and his colleagues.
Lymphocytic infiltration of the skin (Jessner-Kanof) but not reticular erythematous mucinosis occasionally represents clinical manifestations of<i>Borrelia</i>-associated pseudolymphoma
Authors: M. Ziemer, K. Eisendle, H. Müller, B. Zelger
Journal: British Journal of Dermatology (2009)

Lymphocytic infiltration of the skin (LIS) and reticular erythematous mucinosis (REM) are characterized histologically by an inflammatory cutaneous lymphocytic infiltrate similar to the histological appearance of pseudolymphoma.To re-evaluate a large cohort of patients with the clinical and/or histological diagnosis or differential diagnosis of LIS and REM and to assess the evidence for infection with Borrelia.Sixty-nine cases of LIS and 34 cases of REM were retrospectively investigated. Haematoxylin and eosin sections were re-examined, and histological diagnoses were specified and confirmed by clinicopathological correlation. Evidence for Borrelia infection was assessed by immunohistochemistry and focus-floating microscopy (FFM).LIS appeared to serve as a collective term for two main clinicopathological reaction patterns: (i) (tumid) lupus erythematosus (LE) (32 of 69, 46%) and (ii) pseudolymphoma (31 of 69, 45%). Other diagnoses (five of 69, 7%) included polymorphic light eruption, arthropod bite reaction, spongiotic dermatitis, drug eruption and urticaria. Spirochaetes were detected by FFM in 24 of 31 (77%) cases with a pseudolymphomatous reaction, while all nonpseudolymphomatous reactions were negative. Of the cases initially considered as REM, 21 of 34 (62%) were classified as LE, four of 34 (12%) as pseudolymphoma (three of four positive for Borrelia), and five of 34 (15%) as other diagnoses (folliculitis, morphoea, seborrhoeic dermatitis, prurigo and arthropod bite reaction). The diagnosis of Borrelia-associated pseudolymphoma was made significantly more often in those cases where LIS was considered as initial differential diagnosis than REM (P < 0.05).LIS and REM seem to represent clinicopathological reaction patterns. Our results confirm that, after accurate clinicopathological correlation, most cases of both conditions constitute hidden variants of LE. Furthermore, LIS, in contrast to REM, frequently comprises pseudolymphomatous reactions including borrelial lymphocytoma.
Treatment of Chronic Mucocutaneous Candidiasis
Authors: RICHARD H. MEADE
Journal: Annals of Internal Medicine (1977)

Letters1 March 1977Treatment of Chronic Mucocutaneous CandidiasisRICHARD H. MEADE III, M.D.RICHARD H. MEADE III, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-3-314 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptChronic mucocutaneous candidiasis has been exceedingly difficult to treat. The methods reported have had varied success. Transfer factor was effective in the treatment of one anergic girl but failed in the therapy of seven others (1, 2). Amphotericin B has not been more than temporarily effective (3). Thyroid replacement was effective in a boy with myxedema (4). Clotrimazole was so effective in one patient after all other available measures had failed that it is presented here for the consideration of others.The patient, a woman of 40 anergic to mumps,Candida, and to 250 U...References1. PABSTSWANSON HR: Immunotherapy in candidiasis. Lancet 1:1022, 1972 CrossrefMedlineGoogle Scholar2. LEVINSPITLERFUDENBERG ALH: Transfer factor therapy in immune deficiency states. Annu Rev Med 24:175-208, 1973 CrossrefMedlineGoogle Scholar3. MONTESPITTMANMOORE LCW: Chronic mucocutaneous candidiasis. Influence of thyroid status. JAMA 221:156-159, 1972 CrossrefMedlineGoogle Scholar4. MARMORBARNETT ME: Cutaneous anergy without systemic disease. Am J Med 44:979-989, 1968 CrossrefMedlineGoogle Scholar5. HOLTNEWMAN RR: Laboratory assessment of the antimycotic drug clotrimazole. J Clin Pathol 25:1089-1097, 1972 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byClotrimazole nanoemulsion for malaria chemotherapy. Part II: Stability assessment, in vivo pharmacodynamic evaluations and toxicological studiesOral complications in patients with advanced cancerOral Complications in Patients with Advanced CancerChronic mucocutaneous candidosis in monozygotic twinsImmunodeficiency Syndromes and the GutChronic mucocutaneous candidiasisChronic Mucocutaneous CandidiasisA new approach to the use of antifungal agents in infants with persistent oral candidiasisSuccessful treatment of chronic mucocutaneous candidiasis with ketoconazoleResistance to Gonorrhea Possibly Mediated by the Genital Microbial FloraChronic mucocutaneous candidiasis.Topical clotrimazole treatment of chronic mucocutaneous candidiasisTreatment of Chronic Oral Candidiasis with Clotrimazole TrochesSevere Candidal Infections Clinical Perspective, Immune Defense Mechanisms, and Current Concepts of TherapyJOHN E. EDWARDS Jr., M.D., ROBERT I. LEHRER, M.D., E. RICHARD STIEHM, M.D., THOMAS J. FISCHER, M.D., LOWELL S. YOUNG, M.D., F.A.C.P. 1 March 1977Volume 86, Issue 3Page: 314-315KeywordsAmphotericinCandidaCandidiasisMumpsThyroid Issue Published: 1 March 1977 PDF downloadLoading ...
Organs for transplantation.
Authors: S M Gore, A J Holland, C J Hinds
Journal: BMJ (1990)

SIR,-The report of a stone fish "bite" by Drs T Llewellyn and A Fraser-Moodie' illustrates the result of having been "bitten" by a stone fish and makes recommendations for treatment.The stone fish, genus synancejidae, does not bite but injects its venom by way of an adapted dorsal fin2 into the flesh of unwary bathers.The advice given that "the affected part should be immersed in hot water at up to 50°C to denature the venom" is a dangerous suggestion, as not only the venom but also the affected part will be denatured.Moritz and Henriques showed that water at 47°C caused full thickness burns in humans after 18 minutes and that the process was without discomfort in some cases; water at 50°C caused full thickness burns after five minutes.' Between 44°C and 5 1°C the time required to produce irreversible tissue damage is halved for each one degree rise in temperature (from 180 minutes to under two minutes).We think that the advice of Drs Llewellyn and Fraser-Moodie, although given for treatment of a potentially fatal injury, is incorrect and could well result in serious tissue destruction.
Intraclonal heterogeneity and distinct molecular mechanisms characterize the development of t(4;14) and t(11;14) myeloma
Authors: Brian A. Walker, Christopher P. Wardell, Lorenzo Melchor, Sanna Hulkki, Nicola E. Potter, David C. Johnson, Kerry Fenwick, Iwanka Kozarewa, David Gonzalez, Christopher J. Lord, Alan Ashworth, Faith E. Davies, Gareth J. Morgan
Journal: Blood (2012)
Urban Form and Extreme Heat Events: Are Sprawling Cities More Vulnerable to Climate Change Than Compact Cities?
Authors: Brian Stone, Jeremy J. Hess, Howard Frumkin
Journal: Environmental Health Perspectives (2010)

Extreme heat events (EHEs) are increasing in frequency in large U.S. cities and are responsible for a greater annual number of climate-related fatalities, on average, than any other form of extreme weather. In addition, low-density, sprawling patterns of urban development have been associated with enhanced surface temperatures in urbanized areas.In this study. we examined the association between urban form at the level of the metropolitan region and the frequency of EHEs over a five-decade period.We employed a widely published sprawl index to measure the association between urban form in 2000 and the mean annual rate of change in EHEs between 1956 and 2005.We found that the rate of increase in the annual number of EHEs between 1956 and 2005 in the most sprawling metropolitan regions was more than double the rate of increase observed in the most compact metropolitan regions.The design and management of land use in metropolitan regions may offer an important tool for adapting to the heat-related health effects associated with ongoing climate change.
Predicting Coronary Heart Disease in Middle-Aged and Older Persons
Authors: Tavia Gordon
Journal: JAMA (1977)

Of 1,025 men and 1,445 women, aged 49 to 82 years, who were free of coronary heart disease (CHD), 79 men and 63 women subsequently had CHD. Using a risk function based on cholesterol in the high density and low density lipoproteins, systolic blood pressure, left ventricular hypertrophy, and diabetes, less than 2% of the subsequent CHD cases were found in the lowest decile of risk, whereas 25% of the cases for men and 37% for women were found in the highest decile. Predictability held for each specific age group. This predictability was at least as good as that obtained by the usual CHD risk profile at younger ages. (<i>JAMA</i>238:497-499, 1977)