tbuckley/cabot-search huggingface dataset:
Role of Apollon in Human Melanoma Resistance to Antitumor Agents That Activate the Intrinsic or the Extrinsic Apoptosis Pathways
Authors: Elena Tassi, Marina Zanon, Claudia Vegetti, Alessandra Molla, Ilaria Bersani, Valentina Perotti, Marzia Pennati, Nadia Zaffaroni, Michele Milella, Soldano Ferrone, Carmelo Carlo-Stella, Alessandro M. Gianni, Roberta Mortarini, Andrea Anichini
Journal: Clinical Cancer Research (2012)

To assess the role of Apollon in melanoma resistance to intrinsic and extrinsic pathways of apoptosis and to identify strategies to reduce its expression.Apollon expression was assessed in melanoma cells in vitro and in vivo. Apollon modulation and melanoma apoptosis were evaluated by Western blot and/or flow cytometry in response to cytotoxic drugs, mitogen-activated protein/extracellular signal-regulated kinase (MEK)-, BRAF(V600E)-, and mTOR-specific inhibitors, TRAIL and anti-HLA class II monoclonal antibodies (mAb). Mitochondrial depolarization, caspase activation, apoptosis assays, and gene expression profiling were used to test effects of Apollon silencing, by siRNA, on melanoma response to antitumor agents.Apollon was constitutively expressed by melanoma cells, in vitro and in vivo, and at higher levels than in benign melanocytic lesions. Melanoma apoptosis correlated significantly with Apollon protein downmodulation in response to cytotoxic drugs, MEK, or BRAF(V600E)-specific inhibitors. Combinatorial treatment with MEK and mTOR inhibitors and HLA class II ligation, by a specific mAb, promoted Apollon downmodulation and enhanced melanoma apoptosis. Apollon downmodulation induced by antitumor agents was caspase independent, but proteasome dependent. Knockdown of Apollon, by siRNA, triggered apoptosis and/or significantly enhanced melanoma cell death in response to cytotoxic drugs, MEK- and BRAF(V600E)-specific inhibitors, and soluble or membrane-bound TRAIL. Apollon silencing promoted mitochondrial depolarization and caspase-2, caspase-8, caspase-9, and caspase-3 activation in response to different antitumor agents and altered the profile of genes modulated by MEK or BRAF(V600E)-specific inhibitors.Targeting of Apollon may significantly improve melanoma cell death in response to antitumor agents that trigger the intrinsic or the extrinsic apoptosis pathways.
Identifying Ways to Reduce Surgical Errors
Authors: Joseph Richard
Journal: JAMA (1996)

<h3>To the Editor.</h3> —Operating on the wrong patient, the wrong side of the patient, or the wrong body part is a rare but devastating error. Recent instances, widely publicized in the lay press, include amputating the wrong foot,<sup>1</sup>performing mastectomy on the wrong breast,<sup>1</sup>exploring the wrong cerebral hemisphere,<sup>2</sup>and removing the wrong lung from a patient with carcinoma of the lung.<sup>3</sup>Almost always these misadventures happen to patients who are fully draped and under general anesthesia, who cannot point out the mistake as it occurs. In a just-published analysis of the foot amputation error,<sup>4</sup>the operating room schedule and the hospital computer listed the wrong operation, and the patient was indeed draped and asleep when the surgeon entered the operating room. I would like to suggest a method for preventing such errors. When a patient is evaluated prior to surgery, the attending surgeon should at
Expression of chemokines and chemokine receptors in cutaneous CD30+ lymphoproliferative disorders
Authors: T. Yamaguchi, K. Ohshima, K. Karube, R. Kawano, J. Nakayama, J. Suzumiya, M. Kikuchi
Journal: British Journal of Dermatology (2005)

Little is known about the mechanisms involved in skin-specific homing in CD30+ cutaneous lymphoproliferative disorders (CLPD). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites.To investigate tissue samples from patients with CD30+ CLPD for the expression of the chemokine receptors CXCR3, CCR4 and CCR3 and their ligands MIG, TARC and RANTES.Tissue samples from patients with primary cutaneous anaplastic large cell lymphoma (PCALCL, n=12) and lymphomatoid papulosis (LyP, n=13) were studied by immunohistochemistry on paraffin-embedded sections. Immunohistochemical analysis was also performed for CD20 (for B cells), CD45RO and CD3 (for T cells), CD30 and ALK-1. A portion of each skin specimen was stored at -80 degrees C and later examined using monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD15, CD19, CD20 and CD30.CD30+ atypical lymphoid cells were frequently seen in PCALCL, and to a variable degree in LyP. In both disorders there were scattered CD3+ and CD45RO+ atypical lymphoid cells, but CD2, CD5, CD15, CD19, CD20 and ALK-1 showed negative reactivity. In addition, CD4+, but not CD8+, atypical lymphoid cells were occasionally seen in both disorders. CCR3 was expressed by atypical lymphoid cells in 10 of 12 (83%) cases of PCALCL, but in only five of 13 (38%) cases of LyP. CXCR3 was expressed in 11 of 13 (85%) cases of LyP, but in only one of 12 (8%) cases of PCALCL. CCR4 was expressed in 11 of 12 (92%) cases of PCALCL, but in only two of 13 (15%) cases of LyP. RANTES was strongly expressed by lymphoma cells in PCALCL (11 of 12: 92%), but was weak or sporadic in LyP (seven of 13: 54%). TARC showed weak or sporadic reactivity in both LyP and PCALCL, and MIG did not show a distinctive expression pattern in either disorder.We speculate that CCR3 is associated with the autocrine function in PCALCL, as evidenced by CCR3 coexpression with its ligand RANTES. We also found that LyP cells expressed CXCR3, which might support their migration towards the CXCR3 ligand MIG, which is expressed in stromal cells of the skin.
Head of 1992 AIDS Conference Outlines Many Innovations and New Participation
Authors: Marsha F. Goldsmith
Journal: JAMA (1992)

FOR THE FIRST time, delegates from many Eastern European countries are expected to be in attendance when the International Conference on AIDS convenes in Amsterdam, the Netherlands, this July. Their presence—and that of numerous other representatives of developing nations—at this eighth gathering of experts on the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome will be crucial to a "creative renewal" of global efforts against the disease, says conference chair Jonathan M. Mann, MD. "In Eastern Europe, the evidence is already clear that the kinds of societal and economic changes that are occurring are leading to an increase in vulnerability to the spread of HIV," Mann said in a recent interview. As millions of people in areas previously closed to outside influence find all sorts of doors flung open, he says, "it is apparent that the increase in injecting drug use and commercial sex work, along with the social
Trends in Adult Emergency Department Visits in California by Insurance Status, 2005-2010
Authors: Renee Y. Hsia, Julia Brownell, Suzanne Wilson, Nicole Gordon, Laurence C. Baker
Journal: JAMA (2013)

To the Editor:

Emergency department (ED) use has been affected by insurance patterns over time and will likely be further affected by health reform’s expansions of coverage. Because of their disproportionate use of the ED, uninsured patients are often impugned as high, and frequently inappropriate, ED users.1,2 However, recent studies have shown that insured patients can be more frequent utilizers than the uninsured, particularly those with insurance like Medicaid that still leaves them with difficulties in accessing primary care.2-4

We therefore sought to describe recent trends in the association between insurance coverage and ED use in California for non-elderly adult patients, who have experienced the greatest changes in insurance coverage in recent years and are likely to see the biggest shifts as the result of health reform. Previous studies have considered trends in ED use, but predate the recent economic downturn and related insurance changes.2,5
Virus-specific CD8+ cells can switch to interleukin 5 production and induce airway eosinophilia.
Authors: A J Coyle, F Erard, C Bertrand, S Walti, H Pircher, G Le Gros
Journal: The Journal of Experimental Medicine (1995)

Virus infections of the lung are thought to predispose individuals to asthma, a disease characterized by eosinophil infiltration of the airways. CD8+ T cells are an important part of the host response to virus infection, however, they have no reported role in eosinophil recruitment. We developed a mouse model of virus peptide-stimulated CD8+ T cell immune responses in the lung. We found that bystander CD4+ T helper cell type 2 immune responses to ovalbumin switched the virus peptide-specific CD8+ T cells in the lung to interleukin (IL) 5 production. Furthermore, when such IL-5-producing CD8 T cells were challenged via the airways with virus peptide, a significant eosinophil infiltration was induced. In vitro studies indicated that IL-4 could switch the virus-specific CD8+ T cells to IL-5 production. These results could explain the link between virus infection and acute exacerbation of asthma and, perhaps more importantly, they indicate an IL-4-dependent mechanism that would impair CD8+ T cell responses and delay viral clearance from the host.
Anatomical correction of complete transposition of the great arteries and ventricular septal defect in infancy.
Authors: M H Yacoub, R Radley-Smith, C J Hilton
Journal: BMJ (1976)

Two patients, aged 8 weeks and 5 years, with D transposition of great arteries and large ventricular septal defect were treated by transection of both aorta and pulmonary arteries and reattaching them to the appropriate ventricles. This included the origins of the coronary arteries. The ventricular septal defect was closed through a transverse ventriculotomy using a Dacron patch. The younger child was operated on as an emergency because of cyanosis and severe heart failure resistant to intensive medical treatment. The older child had had previous banding of the pulmonary artery at the age of 1 year. In both patients pulmonary artery pressure dropped to below half systemic pressure immediately after the operation. Postoperative progress was satisfactory with relief of cyanosis and heart failure. Early anatomical correction of transposition of the great arteries and ventricular septal defect is feasible and should play an important part in the management of these patients.
CCAAT/Enhancer binding proteins repress the leukemic phenotype of acute myeloid leukemia
Authors: Bao Tran H. Truong, Young Jin Lee, Tracey A. Lodie, Dorothy J. Park, Danilo Perrotti, Naohide Watanabe, H. Phillip Koeffler, Hideaki Nakajima, Daniel G. Tenen, Scott C. Kogan
Journal: Blood (2002)
Correspondence re: M. V. Swamy <b> <i>et al.</i> </b>, Inhibition of COX-2 in Colon Cancer Cell Lines by Celecoxib Increases the Nuclear Localization of Active p53. Cancer Res 2003;63:5239–42.
Authors: Axel H. Schönthal
Journal: Cancer Research (2004)

With great interest did I read the article published in Cancer Research by Swamy et al. [(1)][1] , who investigated the effects of celecoxib on the expression and subcellular localization of the tumor suppressor p53. These authors report that treatment of the colon cancer cell lines HT-29 and HCT-
Abstract 1773: Nucleotide-resolution genomic breakpoint analysis of TMPRSS2-ERG rearrangements in prostate cancer by target-capture next-generation sequencing.
Authors: Christopher Weier, Michael Haffner, Timothy Mosbruger, David Esopi, Jessica Hicks, Qizhi Zheng, William B. Isaacs, Angelo M. De Marzo, William G. Nelson, Srinivasan Yegnasubramanian
Journal: Cancer Research (2013)

Abstract TMPRSS2-ERG translocations occur in approximately 50% of prostate cancers and therefore represent one of the most frequently observed structural rearrangements in all cancers. However, little is known about the genomic architecture of such rearrangements. We therefore designed and optimized a pipeline involving target-capture of TMPRSS2 and ERG genomic sequences coupled with paired-end next generation sequencing to resolve genomic rearrangement breakpoints in TMPRSS2 and ERG at nucleotide resolution in a large series of primary prostate cancer specimens (n = 83). This strategy showed &amp;gt;90% sensitivity and specificity in identifying TMPRSS2-ERG rearrangements, and allowed identification of intra- and inter-chromosomal rearrangements involving TMPRSS2 and ERG with known and novel fusion partners. Our results indicate that rearrangement breakpoints show strong clustering in specific intronic regions of TMPRSS2 and ERG. The observed TMPRSS2-ERG rearrangements often exhibited complex chromosomal architecture associated with several intra- and inter-chromosomal rearrangements. Nucleotide resolution analysis of breakpoint junctions revealed that the majority of TMPRSS2 and ERG rearrangements (∼88%) occurred at or near regions of microhomology or involved insertions of one or more base pairs. This architecture implicates nonhomologous end joining (NHEJ) and microhomology mediated end joining (MMEJ) pathways in the generation of such rearrangements. These analyses have provided important insights into the molecular mechanisms involved in generating prostate cancer-specific recurrent rearrangements. Citation Format: Christopher Weier, Michael Haffner, Timothy Mosbruger, David Esopi, Jessica Hicks, Qizhi Zheng, William B. Isaacs, Angelo M. De Marzo, William G. Nelson, Srinivasan Yegnasubramanian. Nucleotide-resolution genomic breakpoint analysis of TMPRSS2-ERG rearrangements in prostate cancer by target-capture next-generation sequencing. [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 1773. doi:10.1158/1538-7445.AM2013-1773
Identification of functional endothelial protein C receptor in human plasma.
Authors: S Kurosawa, D J Stearns-Kurosawa, N Hidari, C T Esmon
Journal: Journal of Clinical Investigation (1997)

The endothelial cell protein C receptor (EPCR) binds protein C and facilitates activation by the thrombin-thrombomodulin complex. EPCR also binds activated protein C (APC) and inhibits APC anticoagulant activity. In this study, we detected a soluble form of EPCR in normal human plasma. Plasma EPCR appears to be approximately 43, 000 D, and circulates at approximately 100 ng/ml (98.4+/-27.8 ng/ml, n = 22). Plasma EPCR was purified from human citrated plasma using ion exchange, immunoaffinity, and protein C affinity chromatography. Flow cytometry experiments demonstrated that plasma EPCR bound APC with an affinity similar to that previously determined for recombinant soluble EPCR (Kdapp = 30 nM). Furthermore, plasma EPCR inhibited both protein C activation on an endothelial cell line and APC anticoagulant activity in a one-stage Factor Xa clotting assay. The physiological function of plasma EPCR is uncertain, but if the local concentrations are sufficiently high, particularly in disease states, the present data suggest that the soluble plasma EPCR could attenuate the membrane-bound EPCR augmentation of protein C activation and the anticoagulant function of APC.
Consultation process on closing children's cardiac surgery services at Brompton Hospital was fair, judges rule
Authors: C. Dyer
Journal: BMJ (2012)

Three Court of Appeal judges have unanimously ruled that the consultation process to decide which hospitals in England should continue to do paediatric cardiac surgery was carried out lawfully.

The ruling is a blow to the Royal Brompton Hospital, which won a High Court judgment last November quashing the consultation on the “Safe and Sustainable” review ( BMJ 2011;343:d7275, doi:10.1136/bmj.d7275). The review was set up to reconfigure children’s heart surgery so that operations are done in fewer, more specialised centres.

Under the consultation’s “preferred option” the surgery would no longer be carried out at three centres in London …
Cardiovascular Status of Carriers of the Apolipoprotein A-I <sub>Milano</sub> Mutant
Authors: Cesare R. Sirtori, Laura Calabresi, Guido Franceschini, Damiano Baldassarre, Mauro Amato, Jan Johansson, Massimo Salvetti, Cristina Monteduro, Roberto Zulli, Maria L. Muiesan, Enrico Agabiti-Rosei
Journal: Circulation (2001)

Background —Carriers of the apolipoprotein A-I Milano (apoA-I M ) mutant present with very low plasma HDL cholesterol and moderate hypertriglyceridemia, apparently not leading to premature coronary heart disease. The objective of this study was to establish whether this high-risk lipid/lipoprotein profile is associated with structural changes in the carotid arteries and heart, indicative of preclinical atherosclerosis. Methods and Results —Twenty-one A-I M carriers were compared with age- and sex-matched control subjects from the same kindred and with 2 series of matched subjects with primary hypoalphalipoproteinemia (HA). Structural changes in the carotid arteries were defined as the intima-media thickness (IMT) measured by B-mode ultrasound. HA subjects, both recruited among patients attending our Lipid Clinic and blood donors, showed significant thickening of the carotids (average IMT, 0.86±0.25 and 0.88±0.29 mm, respectively) compared with control subjects (average IMT, 0.64±0.12 mm); the apoA-I M carriers instead showed normal arterial thickness (average IMT, 0.63±0.10 mm). Moreover, a significantly higher prevalence of atherosclerotic plaques was found in patients and blood donors with HA (both 57%) compared with apoA-I M carriers (33%) and control subjects (21%). Echocardiographic findings and maximal treadmill ECG did not differ significantly between apoA-I M carriers and control subjects, apart from a slight increase in left ventricular end-diastolic dimension in the carriers. Conclusions —Despite severe HA, carriers of the apoA-I M mutant do not show structural changes in the arteries and heart, in contrast to HA subjects, who are characterized by a marked increase in carotid IMT and increased prevalence of atherosclerotic plaques.
Iron mediates production of a neutrophil chemoattractant by rat hepatocytes metabolizing ethanol.
Authors: R Hultcrantz, D M Bissell, F J Roll
Journal: Journal of Clinical Investigation (1991)

Ethanol metabolism in hepatocytes is accompanied by release of a potent lipid chemoattractant for neutrophils. Production of the factor may initiate the inflammation associated with alcoholic hepatitis. In previous studies with a cytosol system from liver, production was blocked by iron chelators as well as by catalase and superoxide dismutase, suggesting the involvement of oxyradicals in formation of the chemoattractant. These studies have examined the role of iron in intact hepatocytes using cells from rats fed an iron-deficient diet, a control diet or a diet containing 3% carbonyl iron. The iron content averaged 1.4 nmol/mg protein in iron-deficient cells, 6.3 in controls and 135.3 in iron-loaded cells. Hepatocytes from all groups were established in primary culture and incubated with ethanol (10 mM); the medium was assayed for chemoattractant activity for human neutrophils. Cultures from chow-fed or iron-loaded animals produced chemoattractant as previously reported. By contrast, chemoattractant production was undetectable in the iron-deficient cultures. Addition of ferric citrate (10 microM) restored chemoattractant production while increasing cellular iron in the deficient cells less than 50% (to 2.3 nmol/mg protein). Addition of desferrioxamine mesylate to cultures of iron-loaded cells ablated chemoattractant production. The data provide evidence for the importance of hepatocellular iron in production of this alcohol-related lipid chemoattractant and suggest that a small intracellular pool of "free" iron plays a critical role.
Platelet-activating Factor–mediated NF-κB Dependency of a Late Anaphylactic Reaction
Authors: Il-Whan Choi, Young-Suk Kim, Dae-Ki Kim, Jung-Hwa Choi, Kook-Heon Seo, Shun-Young Im, Keun-Sang Kwon, Myung-Shik Lee, Tai-You Ha, Hern-Ku Lee
Journal: The Journal of Experimental Medicine (2003)

Anaphylaxis is a life-threatening systemic allergic reaction with the potential for a recurrent or biphasic pattern. Despite an incidence of biphasic reaction between 5 and 20%, the molecular mechanism for the reaction is unknown. Using a murine model of penicillin V–induced systemic anaphylaxis, we show an autoregulatory cascade of biphasic anaphylactic reactions. Induction of anaphylaxis caused a rapid increase in circulating platelet-activating factor (PAF) levels. In turn, the elevated PAF contributes to the early phase of anaphylaxis as well as the subsequent activation of the nuclear factor (NF)-κB, a crucial transcription factor regulating the expression of many proinflammatory cytokines and immunoregulatory molecules. The induction of NF-κB activity is accompanied by TNF-α production, which, in turn, promotes late phase PAF synthesis. This secondary wave of PAF production leads eventually to the late phase of anaphylactic reactions. Mast cells do not appear to be required for development of the late phase anaphylaxis. Together, this work reveals the first mechanistic basis for biphasic anaphylactic reactions and provides possible therapeutic strategies for human anaphylaxis.
Patients rate hospitals high on cleanliness but low on food
Authors: G. Iacobucci
Journal: BMJ (2013)

Hospitals in England have scored highly in the first results of a new assessment programme measuring patient’s views of non-clinical services.

Initial findings from the Patient-Led Assessments of the Care Environment (PLACE) programme—a voluntary initiative covering both the NHS and the independent sector—show that hospitals scored an average of around eight out of 10 on measures including catering, the condition of their buildings, and fixtures and fittings.

The highest average scores were for cleanliness, and the lowest were for food and hydration.

The results, published by the Health and Social Care …
The relationship of oxidative stress to vascular health in humans
Authors: Salman Ashfag, Jerome l. Abramson, Steven D. Rhodes, Sean C. Beinart, Claudine Jurkovitz, Jovonne K. Williams, Viola Vaccarino, Arshed A. Quyyumi, William S. Weintraub, David G. Harrison
Journal: Journal of the American College of Cardiology (2003)
THE INFLUENCE OF FORMULATION ON TOPICAL CORTICOSTEROID ACTIVITY
Authors: I. SARKANY, J. W. HADGRAFT
Journal: British Journal of Dermatology (1969)

SUMMARY.— The factors influencing topical corticosteroid activity are primarily concerned with selection of the derivative with the most suitable physico-chemical characteristics and to a less extent with the choice of the vehicle. Dissolving the corticosteroid in a suitable solvent appears to enhance skin absorption. Its solubility in the vehicle influences the amount of corticosteroid released and greatest release is obtained from preparations in which the corticosteroid is dissolved in its maximal solubility concentration. Other factors, such as the effect of the solvent on the skin barrier, the degree of hydration of the horny layer and the temperature also play a part. The effect of vehicles on corticosteroids has been investigated in vitro using artificial and natural membranes. These methods may be useful in screening new products, hut more reliable assessment can be made by in vivo studies. Animal experiments cannot be applied without reservations to human conditions. Experimental and clinical evaluation in humans presents its own problems, especially from the point of view of quantitative assessment, but it offers the most reliable information on the influence of formulation on topical corticosteroid activity.