tbuckley/cabot-search huggingface dataset:
E6-Associated Protein Is Required for Human Papillomavirus Type 16 E6 to Cause Cervical Cancer in Mice
Authors: Anny Shai, Henry C. Pitot, Paul F. Lambert
Journal: Cancer Research (2010)

High-risk human papillomaviruses (HPV) cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins, including Bak, E6BP1, and E6TP1, and proteins that contain PDZ domains, such as hScrib and hDlg. Many of these activities are thought to contribute to the role of E6 in carcinogenesis. The interaction of E6 with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through the ability of E6 to recruit the ubiquitin ligase E6-associated protein (E6AP) into complexes with these cellular proteins, resulting in their ubiquitin-mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating acute and oncogenic phenotypes of E6, including induction of epithelial hyperplasia, abrogation of DNA damage response, and induction of cervical cancer. Loss of E6AP had no discernible effect on the ability of E6 to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of the oncogenic potential of E6 in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer.
Permanent CD8+ T Cell Depletion Prevents Proteinuria in Active Heymann Nephritis
Authors: Mark J. Penny, Rochelle A. Boyd, Bruce M. Hall
Journal: The Journal of Experimental Medicine (1998)

Active Heymann nephritis (HN) is a rat model of human idiopathic membranous nephropathy in which injury is thought to be mediated by membrane attack complex of complement (MAC) activated by antibody (Ab) to glomerular epithelial cells. Recent work has shown that HN develops in C6-deficient rats which cannot assemble MAC, and that infiltration of activated cytotoxic CD8(+) T cells and macrophages into glomeruli coincides with proteinuria. This study examined the role of CD8(+) T cells in mediating glomerular injury in HN by permanent CD8(+) cytotoxic T cell depletion via adult thymectomy (ATx) and anti-CD8 mAb. Groups of rats were depleted of CD8(+) T cells either before immunization for HN or 6 wk after immunization when Ab responses and glomerular IgG deposition were well established. These were compared with groups of HN, ATx/HN, and complete Freund's adjuvant (CFA) controls. Neither group of CD8(+) T cell-depleted rats developed proteinuria, although there was normal development and deposition of Ab. CD8(+) T cell-depleted rats developed neither T cell or macrophage infiltrates nor their effector cytokines, which are present in glomeruli of rats with HN. Examination of lymph node (LN) draining sites of immunization showed these findings were not explained by altered immune events within these LNs. It was concluded that CD8(+) cytotoxic T cells are essential to the mediation of glomerular injury in HN and may be relevant to the pathogenesis and treatment of membranous nephropathy.
HIV seroprevalence among patients admitted to two psychiatric hospitals
Authors: F Cournos, M Empfield, E Horwath, K McKinnon, I Meyer, H Schrage, C Currie, B Agosin
Journal: American Journal of Psychiatry (1991)

The authors determined the seroprevalence of HIV-1 among patients admitted to two psychiatric hospitals in New York City.Patients consecutively admitted to an acute psychiatric unit in Manhattan and a large state hospital in Queens were anonymously tested for HIV-1 antibodies from December 1989 through July 1990. Test results were linked to age, gender, ethnicity, and two risk behaviors: male homosexual activity and injection drug use.Blood was obtained from 83.0% of the eligible patients. The prevalence of HIV was 5.5% (25 of 451). Black patients accounted for 38.0% of the patients tested and 76.0% of positive results (N = 19), a rate of 11.1% for this group. The rate of seropositivity was comparable in women and men. Clinicians had charted risk behavior for nine (36.0%) of the 25 HIV-positive patients. Infection control records suggested that clinicians were aware of seven (28.0%) of the positive cases.One in every 18 patients admitted to two public psychiatric hospitals in New York City was HIV positive. Clinical staff largely failed to identify HIV-positive patients. Ethnicity and a history of homosexual activity among men or use of injected drugs were strongly associated with seropositivity. This pattern of infection may be linked to needle sharing and/or sexual activity with partners who have shared needles. Future research should clarify how psychiatric illness affects risk-taking behavior, focus on improving detection by clinicians, and identify effective prevention strategies in this population.
Prophylactic Treatment for Rash Induced By Egfr Inhibitor Improves Rash Without Compromising on Efficacy the Pancanadian Rash Trial: a Randomized Phase III Trial in Nsclc
Authors: B. Melosky, R. Burkes, Q.S. Chu, D. Hao, C. Ho, H. Anderson, C. Lee, N.B. Leighl, N. Murray, S. Sun, R. Winston, W. Lam, J. Laskin
Journal: Annals of Oncology (2014)
Changes in Neurologic Function Tests May Predict Neurotoxicity Caused by Ixabepilone
Authors: James J. Lee, Jennifer A. Low, Earllaine Croarkin, Rebecca Parks, Arlene W. Berman, Nitin Mannan, Seth M. Steinberg, Sandra M. Swain
Journal: Journal of Clinical Oncology (2006)

Purpose To investigate baseline factors and neurologic function tests (NFTs) that may predict the development of grade 2 or higher peripheral neuropathy (PN) after treatment with ixabepilone, an epothilone microtubule-stabilizing agent with antitumor activity. Patients and Methods Advanced breast cancer patients were treated with ixabepilone (6 mg/m 2 ) for 5 consecutive days every 3 weeks in a phase II clinical trial. Physical examinations, questionnaires, nerve conduction studies, and NFTs, including the Jebsen Test of Hand Function (JTH) and the Grooved Pegboard Test (GPT), were performed at baseline and during subsequent cycles. Results Forty-seven patients assessable for PN received a median of five cycles of therapy (range, one to 22 cycles). Nine of these patients developed grade 2 PN, and two developed grade 3 PN, with a median time to onset of 144 days (range, 6 to 189 days). Among these 11 patients, PN resolved in eight patients, with a median of 15 days (range, 6 to 346 days) after onset, but PN did not resolve in three patients during follow-ups at 76, 361, and 746 days after onset. GPT and changes of JTH scores at onset of PN were significantly different between patients with and without PN at comparable follow-up times (P = .006 and P = .002, respectively). Changes in GPT and JTH scores over the first two cycles were often associated with the development of PN by exploratory actuarial analysis. Conclusion Serious ixabepilone-induced neuropathy was relatively rare on the treatment schedule used. NFTs, such as JTH and GPT, may have utility for predicting PN, but further testing is needed.
Transcriptional regulation of miR-224 upregulated in human HCCs by NFκB inflammatory pathways
Authors: Cecilia Scisciani, Stefania Vossio, Francesca Guerrieri, Valeria Schinzari, Rossana De Iaco, Paolo D’Onorio de Meo, Melchiorre Cervello, Giuseppe Montalto, Teresa Pollicino, Giovanni Raimondo, Massimo Levrero, Natalia Pediconi
Journal: Journal of Hepatology (2011)
Dual origin of mouse spleen macrophages.
Authors: R van Furth, M M Diesselhoff-den Dulk
Journal: The Journal of Experimental Medicine (1984)

The present study concerns the isolation, characterization, origin, and kinetics of spleen macrophages. The spleen was first perfused in situ to remove monocytes from the vascular bed and then dissected and treated with collagenase. The macrophages in the cell suspension thus obtained were characterized morphologically and cytochemically and then quantitated. The spleen cell suspension was incubated for 24 h in Leighton tubes to obtain an enriched glass-adherent population of macrophages for characterization and [3H]thymidine-labeling studies. Almost all of the adhering macrophages were esterase positive, had Fc and C3b receptors, and ingested EIgG and opsonized bacteria. In vitro labeling with [3H]thymidine showed that approximately 5% of the mononuclear phagocytes in the spleen synthesize DNA and must be considered to be dividing cells. The course of the number of labeled monocytes and macrophages after a single injection of [3H]thymidine indicates migration of monocytes into the spleen, where they become macrophages. Calculation of the influx of monocytes into the spleen and of the local production of macrophages by DNA-synthesizing mononuclear phagocytes showed that under steady-state conditions, 55% of the population of spleen macrophages is supplied by monocyte influx and 45% by local production. This means that there is a dual origin of spleen macrophages. The mean turnover time calculated with the value for the efflux of spleen macrophages is 6.0 d.
Treatment of high-grade glioma in children and adolescents
Authors: T. J. MacDonald, D. Aguilera, C. M. Kramm
Journal: Neuro-Oncology (2011)

Pediatric high-grade gliomas (HGGs)--including glioblastoma multiforme, anaplastic astrocytoma, and diffuse intrinsic pontine glioma--are difficult to treat and are associated with an extremely poor prognosis. There are no effective chemotherapeutic regimens for the treatment of pediatric HGG, but many new treatment options are in active investigation. There are crucial molecular differences between adult and pediatric HGG such that results from adult clinical trials cannot simply be extrapolated to children. Molecular markers overexpressed in pediatric HGG include PDGFRα and P53. Amplification of EGFR is observed, but to a lesser degree than in adult HGG. Potential molecular targets and new therapies in development for pediatric HGG are described in this review. Research into bevacizumab in pediatric HGG indicates that its activity is less than that observed in adult HGG. Similarly, tipifarnib was found to have minimal activity in pediatric HGG, whereas gefitinib has shown greater effects. After promising phase I findings in children with primary CNS tumors, the integrin inhibitor cilengitide is being investigated in a phase II trial in pediatric HGG. Studies are also ongoing in pediatric HGG with 2 EGFR inhibitors: cetuximab and nimotuzumab. Other novel treatment modalities under investigation include dendritic cell-based vaccinations, boron neutron capture therapy, and telomerase inhibition. While the results of these trials are keenly awaited, the current belief is that multimodal therapy holds the greatest promise. Research efforts should be directed toward building multitherapeutic regimens that are well tolerated and that offer the greatest antitumor activity in the setting of pediatric HGG.
Epicardium and Myocardium Separate From a Common Precursor Pool by Crosstalk Between Bone Morphogenetic Protein– and Fibroblast Growth Factor–Signaling Pathways
Authors: Bram van Wijk, Gert van den Berg, Radwan Abu-Issa, Phil Barnett, Saskia van der Velden, Martina Schmidt, Jan M. Ruijter, Margaret L. Kirby, Antoon F.M. Moorman, Maurice J.B. van den Hoff
Journal: Circulation Research (2009)

The epicardium contributes to the majority of nonmyocardial cells in the adult heart. Recent studies have reported that the epicardium is derived from Nkx2.5-positive progenitors and can differentiate into cardiomyocytes. Not much is known about the relation between the myocardial and epicardial lineage during development, whereas insights into these embryonic mechanisms could facilitate the design of future regenerative strategies.Acquiring insight into the signaling pathways involved in the lineage separation leading to the differentiation of myocardial and (pro)epicardial cells at the inflow of the developing heart.We made 3D reconstructions of Tbx18 gene expression patterns to give insight into the developing epicardium in relation to the developing myocardium. Next, using DiI tracing, we show that the (pro)epicardium separates from the same precursor pool as the inflow myocardium. In vitro, we show that this lineage separation is regulated by a crosstalk between bone morphogenetic protein (BMP) signaling and fibroblast growth factor (FGF) signaling. BMP signaling via Smad drives differentiation toward the myocardial lineage, which is inhibited by FGF signaling via mitogen-activated protein kinase kinase (Mek)1/2. Embryos exposed to recombinant FGF2 in vivo show enhanced epicardium formation, whereas a misbalance between FGF and BMP by Mek1/2 inhibition and BMP stimulation causes a developmental arrest of the epicardium and enhances myocardium formation at the inflow of the heart.Our data show that FGF signaling via Mek1/2 is dominant over BMP signaling via Smad and is required to separate the epicardial lineage from precardiac mesoderm. Consequently, myocardial differentiation requires BMP signaling via Smad and inhibition of FGF signaling at the level of Mek1/2. These findings are of clinical interest for the development of regeneration-based therapies for heart disease.
CHRONIC AMOEBIASIS AND CHRONIC APPENDICITIS
Authors: W. Wilkinson
Journal: BMJ (1935)

Since writing this report a case of scarletfever has recently arisen (June 18th) in a' boy who was a Dick- positive contact with the first case of scarlet fever last term, and who had then been passively immunized.In consequence of this case, all the available passively im- munized boys of last term, thirty-two in number, have b3en Dick-tested again, with the result that thirty-one have been found to be positive and only one negative.I most gratefully acknowledge my thanks to Dr. J. Alison Glover and Dr. Scott for their advice
Phase I Trial and Pharmacokinetic Study of Raltitrexed in Children with Recurrent or Refractory Leukemia: A Pediatric Oncology Group Study
Authors: Terzah M. Horton, Susan M. Blaney, Anne-Marie Langevin, John Kuhn, Barton Kamen, Stacey L. Berg, Mark Bernstein, Steven Weitman
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To evaluate the toxicity, antileukemic activity, and pharmacology of raltitrexed administered weekly for 3 weeks to patients with refractory or recurrent leukemia. Experimental Design: Raltitrexed was administered as a 15-minute infusion for 3 consecutive weeks every 5 weeks, at doses ranging from 1.3 to 2.8 mg/m2. The first course was used to determine the dose-limiting toxicities and maximum tolerated dose. Correlative studies included an assessment of raltitrexed pharmacokinetics and measurement of plasma 2′-deoxyuridine concentrations, a surrogate measure of thymidylate synthase inhibition. Results: Twenty-one children (18 evaluable) with refractory leukemia received 25 courses of raltitrexed. The dose-limiting toxicity was reversible elevation in liver transaminases at the 2.8-mg/m2 dose level and the maximum tolerated dose was 2.1 mg/m2 per dose. Pharmacokinetics were best characterized by a two-compartment model with a clearance of 139 mL/min/m2 (8.3 L/h/m2), a 2.4-L volume of distribution, an initial half-life (t1/2α) of 6 minutes, and a terminal half-life (t1/2β) of 45 minutes. There were three objective responses. Conclusions: Raltitrexed was well tolerated when administered as a single agent to children with recurrent or refractory leukemia. We observed preliminary evidence of antileukemia activity using this weekly dosing schedule and these observations support further evaluation of raltitrexed in this population.
Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia.
Authors: T van der Poll, S M Coyle, K Barbosa, C C Braxton, S F Lowry
Journal: Journal of Clinical Investigation (1996)

Short-term preexposure of mononuclear cells to epinephrine inhibits LPS-induced production of TNF, whereas preexposure for 24 h results in increased TNF production. To assess the effects of epinephrine infusions of varying duration on in vivo responses to LPS, the following experiments were performed: (a) Blood obtained from eight subjects at 4-24 h after the start of a 24-h infusion of epinephrine (30 ng/kg per min) produced less TNF after ex vivo stimulation with LPS compared with blood drawn before the start of the infusion, and (b) 17 healthy men who were receiving a continuous infusion of epinephrine (30 ng/kg per min) started either 3 h (EPI-3; n = 5) or 24 h (EPI-24; n = 6) were studied after intravenous injection of LPS (2 ng/kg, lot EC-5). EPI-3 inhibited LPS-induced in vivo TNF appearance and also increased IL-10 release (both P < 0.005 versus LPS), whereas EPI-24 only attenuated TNF secretion (P = 0.05). In separate in vitro experiments in whole blood, epinephrine increased LPS-induced IL-10 release by a combined effect on alpha and beta adrenergic receptors. Further, in LPS-stimulated blood, the increase on IL-10 levels caused by epinephrine only marginally contributed to concurrent inhibition of TNF production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may have a net antiinflammatory effect on the cytokine network early in the course of systemic infection.
Surimi and native codfish contain a common allergen identified as a 63‐kDa protein
Authors: E. Mata, C. Favier, D. A. Moneret‐Vautrin, J. P. Nicolas, L. Han Ching, J.L Guéant
Journal: Allergy (1994)

We have compared the allergenicity of codfish and surimi (prepared from codfish) by skin testing, specific IgE-RIA, and leukocyte histamine release (LHR) in six fish-allergic patients. Prick tests were positive for codfish and, to a lesser extent, surimi. The percentages of labeled anti-IgE bound to surimi-Sepharose were 1.55 +/- 0.19% and 3-6% with control and patient sera, respectively. Inhibition of the surimi protein-Sepharose IgE-RIA was greatest (80%) at protein concentrations of 13.4 and 408.5 micrograms/ml for codfish and surimi extract, respectively. The allergenic protein was isolated by gel filtration and subjected to SDS-PAGE. The eluate from codfish contained several proteins ranging from 13 to 63 kDa, while the eluate from surimi contained a single 63-kDa protein. It was concluded that surimi contained a single allergenic protein.
Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration
Authors: M. Stone, T. Laughren, M L. Jones, M. Levenson, P C. Holland, A. Hughes, T. A Hammad, R. Temple, G. Rochester
Journal: BMJ (2009)

To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults.Meta-analysis of 372 double blind randomised placebo controlled trials.Drug development programmes for any indication in adults.99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were women. Indications for treatment were major depression (45.6%), other depression (4.6%), other psychiatric disorders (27.6%), and non-psychiatric disorders (22.2%).Suicidal behaviour (completed suicide, attempted suicide, or preparatory acts) and ideation.For participants with non-psychiatric indications, suicidal behaviour and ideation were extremely rare. For those with psychiatric indications, risk was associated with age. For suicidal behaviour or ideation and for suicidal behaviour only, the respective odds ratios were 1.62 (95% confidence interval 0.97 to 2.71) and 2.30 (1.04 to 5.09) for participants aged <25, 0.79 (0.64 to 0.98) and 0.87 (0.58 to 1.29) for those aged 25-64, and 0.37 (0.18 to 0.76) and 0.06 (0.01 to 0.58) for those aged >or=65. When age was modelled as a continuous variable, the odds ratio for suicidal behaviour or ideation declined at a rate of 2.6% per year of age (-3.9% to -1.3%, P=0.0001) and the odds ratio for suicidal behaviour declined at a rate of 4.6% per year of age (-7.4% to -1.8%, P=0.001).Risk of suicidality associated with use of antidepressants is strongly age dependent. Compared with placebo, the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents. The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged >or=65.
Bridging the gap in rheumatology
Authors: J. E McDonagh
Journal: Annals of the Rheumatic Diseases (2000)

### PRESENTATION AND MANAGEMENT

Louise is now 18 years old. She is white and developed erosive, polyarticular psoriatic arthritis with significant skin involvement when she was 10 years old . She was referred to the paediatric rheumatology team at the age of 13 having previously been treated with non-steroidal anti-inflammatory drugs, sulfasalazine and intra-articular corticosteroids. She was subsequently treated with further multiple intra-articular corticosteroid injections under general anaesthetic, oral methotrexate (maximum 20 mg/week) and naproxen (20 mg/kg/day).#### Key messages

Her disease failed to remit and oral methotrexate was replaced with weekly subcutaneous methotrexate (maximum 25 mg/week, given by Louise's mother) and continuous oral daily prednisolone (0.5 mg/kg/day). After three months of subcutaneous methotrexate treatment, Louise developed persistently abnormal liver function tests (maximum alanine transaminase (ALT) =286 IU/l, alkaline phosphatase (ALP) =718 IU/l). Methotrexate was subsequently omitted and re-introduced at a lower dose but to the detriment of the arthritis, which flared requiring increased prednisolone treatment. In view of the desire to continue methotrexate, a liver biopsy was performed that showed only sinusoidal dilatation with no chronic damage evident. The methotrexate was continued and a repeat liver biopsy a year later remained unchanged. The liver function tests gradually resolved with control of the disease and are currently as follows: ALT=17 IU/l, ALP= 339 IU/l.

When Louise was 15 years old, in view of the difficulty controlling her disease without concomitant oral corticosteroids, potential addition of cyclosporin was discussed. She adamantly refused this medication in view of the potential side effects, particularly the hirsuitism and gum hyperplasia. As a compromise, she agreed to take …
PUSTULAR ERUPTION WITH EOSINOPHILIC ABSCESSES
Authors: DANILO V. STEVANOVIC
Journal: British Journal of Dermatology (1971)

Journal Article PUSTULAR ERUPTION WITH EOSINOPHILIC ABSCESSES Get access DANILO V. STEVANOVIC DANILO V. STEVANOVIC Department of Dermatology, Medical Faculty, Belgrade, Yugoslavia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 85, Issue 2, 1 August 1971, Pages 134–139, https://doi.org/10.1111/j.1365-2133.1971.tb07198.x Published: 01 August 1971 Article history Accepted: 23 April 1971 Published: 01 August 1971