tbuckley/cabot-search huggingface dataset:
RHEX in the mix of erythropoietin signaling molecules
Authors: Hal E. Broxmeyer
Journal: The Journal of Experimental Medicine (2014)

The Journal of Experimental Medicine Erythropoietin (EPO) is of immense practical clinical utility in the treatment of anemia, and insight into EPO-regulated signaling pathways may reveal new targets for the treatment of dysregulated erythropoiesis.While significant headway has been made in understanding the intracellular signals mediating the effects of EPO through the homodimeric EPO receptor (EPOR), we clearly don't know all the intracellular mediators involved.In this issue, Verma et al. report a novel mediator of EPO-dependent expansion of human erythroid progenitor cells and development of erythroblasts, which they have named regulator of human erythroid cell expansion (RHEX).Applying a global phosphotyrosine (PY) phosphoproteomic approach, the authors identified an uncharacterized 26K open reading frame that was rapidly and highly tyrosine-phosphorylated at two sites after EPO stimulation.RHEX has no significant homology with known proteins and, although wellconserved in humans and other primates, it is not found in the genomes of rats, mice, or lower vertebrates.RHEX knockdown in an EPO-dependent human cell line attenuated cell growth and activation of ERK1 and ERK2, with no effect on cell death.In purified populations of human erythroid progenitor cells, RHEX knockdown delayed the formation of maturing erythroblasts.Coimmunoprecipitation experiments indicated that RHEX associates with the versatile adaptor protein GRB2 following EPO stimulation.This outstanding paper opens up a number of important questions regarding the function of RHEX and the regulation of EPOR signaling.Is RHEX involved in the intracellular signaling of other cytokines?If so, does EPO signaling compete with other cytokine signaling pathways for GRB2 binding to RHEX?In addition to the homodimeric EPOR, a heterodimeric EPOR (EPOR chain and CD131, the common b-chain of GM-CSFR and IL-3R), which is present on some normal and cancer cell types, mediates nonerythropoietic effects of EPO.Is RHEX also an intermediary in signaling through the heterodimeric EPOR?Finally, it is of interest that RHEX was not detected in rats, mice, and lower vertebrates.Why is this?And how does EPO-EPOR signaling differ in different species?Although the investigators chose to focus on RHEX, their PY-phosphoproteomic analysis identified other EPO-induced candidate targets, including molecular adaptors, serine/ threonine kinases, tyrosine phosphatases, ubiquitin factors, and cell cycle regulators, that should provide for continued productive analysis of EPO-induced signaling.The EPO-EPOR signaling gray box is opening up, and with it will come greater insight into EPO's actions and its modulation for clinical advantage.
The role of nanoparticle concentration-dependent induction of cellular stress in the internalization of non-toxic cationic magnetoliposomes
Authors: Stefaan J.H. Soenen, Eszter Illyes, Dries Vercauteren, Kevin Braeckmans, Zsuzsa Majer, Stefaan C. De Smedt, Marcel De Cuyper
Journal: Biomaterials (2009)
Enrollment in the Health Alliance Plan HMO Is Not an Independent Risk Factor for Coronary Artery Bypass Graft Surgery
Authors: Gaetano Paone, Robert S.D. Higgins, Trey Spencer, Norman A. Silverman
Journal: Circulation (1995)

Background Henry Ford Hospital is the sole provider of cardiac surgical services for the Health Alliance Plan, a health maintenance organization (HMO) that presently serves 450 000 enrollees. Methods and Results To determine the effect of managed care referral patterns on the outcome of coronary artery bypass graft (CABG) surgery, we retrospectively reviewed two concurrent groups of patients, 569 HMO patients and 225 patients with fee-for-service (FFS) insurance, who had undergone isolated primary CABG surgery between January 1, 1990 and January 31, 1994. The 605 patients with Medicare operated on during the same time frame were excluded to obviate age bias. Age, sex, use of cardiac medications, history of prior percutaneous transluminal coronary angioplasty or thrombolytic therapy, history of recent and remote myocardial infarction, extent of coronary disease, presence of preexisting comorbid conditions, and incidence of unstable clinical syndromes and left ventricular dysfunction (ejection fraction&lt;40%) were comparable for both groups. Inhospital mortality (HMO group, 1.9%; FFS group, 2.2%), mean ICU stay (HMO, 2.6±0.3 days; FFS, 2.3±0.3 days), and total hospital length of stay (HMO, 9.8±0.8 days; FFS, 8.6±0.6 days) were likewise similar. Conclusions These data refute the notion that the gatekeeper mentality often associated with managed-care health insurance vehicles results in delayed referral of patients with coronary artery disease and results in suboptimal outcome.
Suppression of Epidermal Growth Factor–Induced Phospholipase C Activation Associated With Actin Rearrangement in Rat Hepatocytes in Primary Culture
Authors: Shunsuke Nojiri, Jan Hoek
Journal: Hepatology (2000)

Hepatocytes maintained in primary culture for periods of 1 to 24 hours exhibited a rapid decline in epidermal growth factor (EGF)-induced activation of phospholipase C (PLC), as was evident in a loss of EGF-induced inositol 1,4,5-trisphosphate (IP(3)) formation and mobilization of Ca(2+) from intracellular Ca(2+) stores. The loss of PLC activation was not the result of a decrease in EGF receptor or phospholipase C-gamma1 (PLCgamma1) protein levels, nor the result of a loss of tyrosine phosphorylation of these proteins, but was associated with a decrease in EGF-induced translocation of PLCgamma1 to the Triton-insoluble fraction, presumably reflecting binding to the actin cytoskeleton. Disruption of F-actin by treatment of cultured hepatocytes with cytochalasin D recovered the EGF-induced IP(3) formation and Ca(2+) mobilization to the same level and with the same dose-response relationship as was obtained in freshly isolated cells. Analysis of PLCgamma1 colocalization with F-actin by confocal microscopy showed that PLCgamma1 was mostly distributed diffusely in the cytosol, both in freshly plated cells and in cells in culture for 24 hours, despite marked differences in actin structures. EGF stimulation caused a modest redistribution of PLCgamma1 and a detectable increase in colocalization with cortical actin structures in freshly plated cells or in cytochalasin D-treated cells, but in cells that had been maintained and spread in culture only a limited PLCgamma1 relocation was detected to specific actin-structure associated with lamellipodia and membrane ruffles. We conclude that actin cytoskeletal structures can exert negative control over PLCgamma1 activity in hepatocytes and the interaction of the enzyme with specific actin structures dissociates PLCgamma1 tyrosine phosphorylation from activation of its enzymatic activity.
The antiwrinkle effect of topical concentrated 2-dimethylaminoethanol involves a vacuolar cytopathology
Authors: G. Morissette, L. Germain, F. Marceau
Journal: British Journal of Dermatology (2007)

Journal Article The antiwrinkle effect of topical concentrated 2‐dimethylaminoethanol involves a vacuolar cytopathology Get access G. Morissette, G. Morissette Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Québec QC, G1V 4G2, Canada *Laboratoire d'Organogénèse Expérimentale, Hôpital du Saint‐Sacrement du CHA, Québec QC, G1S 4L8, Canada Search for other works by this author on: Oxford Academic Google Scholar L. Germain, L. Germain Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Québec QC, G1V 4G2, Canada *Laboratoire d'Organogénèse Expérimentale, Hôpital du Saint‐Sacrement du CHA, Québec QC, G1S 4L8, Canada Search for other works by this author on: Oxford Academic Google Scholar F. Marceau F. Marceau Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Québec QC, G1V 4G2, Canada *Laboratoire d'Organogénèse Expérimentale, Hôpital du Saint‐Sacrement du CHA, Québec QC, G1S 4L8, Canada Correspondence: François Marceau. E‐mail: francois.marceau@crchul.ulaval.ca Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 3, 1 March 2007, Pages 433–439, https://doi.org/10.1111/j.1365-2133.2007.07681.x Published: 01 March 2007
Challenges in Optimizing Isotretinoin Use for Acne Vulgaris
Authors: Thomas J. McIntee, Anna L. Bruckner
Journal: JAMA Dermatology (2013)

Acne vulgaris is one of the most common skin disorders affecting adolescents and young adults. Food and Drug Administration approval of isotretinoin in 1982 dramatically changed the management of nodulocystic and severe, recalcitrant acne. Isotretinoin remains the only acne treatment associated with complete remission and �cure� of nodulocystic acne. Yet despite the dramatic effect of the drug, disease relapse can occur after isotretinoin therapy.

Multiple treatment algorithms and dosing regimens have been proposed for isotretinoin, and a cumulative dose of 120 to 150 mg/kg is widely accepted as the standard treatment protocol. Alternative strategies have been designed to optimize drug dosing to achieve acceptable clinical results while minimizing adverse effects. Such regimens range from 0.2 mg/kg/d to greater than 2 mg/kg/d of isotretinoin with variations in treatment duration. These differing opinions on the dosing of isotretinoin expose a gap in our medical knowledge about optimal isotretinoin dosing for acne vulgaris.
The functional meaning of reverberations for sensoric and contextual encoding
Authors: Wolfgang Klimesch
Journal: Behavioral and Brain Sciences (1995)

Abstract Amit argues that the local neuronal spike rate that persists (reverberating) in the absence of the eliciting stimulus represents the code of the eliciting stimulus. Based on the general argument that the inferred functional meaning of reverberation depends in part on the type of representational assumptions, reverberations may only be important for the encoding of contextual information.
FIBRINOLYTIC ACTIVITY AND THE SKIN
Authors: AMAL K. KURBAN
Journal: British Journal of Dermatology (1970)

Journal Article FIBRINOLYTIC ACTIVITY AND THE SKIN Get access AMAL K. KURBAN AMAL K. KURBAN Institute of Dermatology, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue 1, 1 January 1970, Pages 76–77, https://doi.org/10.1111/j.1365-2133.1970.tb02196.x Published: 01 January 1970
Blood Pressure Reduction and the Risk of Myocardial Infarction
Authors: Jan Staessen
Journal: JAMA (1990)

To the Editor.—  Recently, Alderman et al 1 have reported a J-shaped relationship between the degree of blood pressure fall, induced by treatment, and the occurrence of myocardial infarction in previously untreated patients with mild to moderate hypertension, followed up for an average of 4.2 years. Since both large and small reductions in diastolic blood pressure were associated with a higher incidence of myocardial infarction, these authors suggested that a moderate reduction in diastolic blood pressure (7 to 17 mm Hg) should perhaps be the goal of treatment for mild and moderate hypertensives. 1   Two other studies, 2,3 one of which was double-blind, 3 have reported a J-shaped relation between treated pressure and mortality in both actively treated hypertensives and control patients. Furthermore, Alderman et al 1 did not predict events from the treated blood pressure at a constant interval following entry. Instead, they related outcome to the blood pressure
Squaring circle time
Authors: D. Spence
Journal: BMJ (2009)

I stood on the stage holding my spear. A bit part. Mary and Joseph held centre stage, and the narrator’s voice boomed around us. Like many primary school heroes, Joseph ended up in jail, and Mary became a teen mother. I was an academic nobody, with no label of dyslexia and no classroom assistant. But I could tell a joke, was good at conkers and football cards, and would stick up for my friends. We didn’t try to punch the teacher, and in turn teachers tried their …
Interaction of Steroid Hormone Receptors with the Transcription Initiation Complex
Authors: MIGUEL BEATO, AURORA SÁNCHEZ-PACHECO
Journal: Endocrine Reviews (1996)

I. IntroductionREGULATION of gene expression by steroid hormones is a traditional field of molecular endocrinology. The hormones act by binding to intracellular receptors, which themselves orchestrate the transcriptional response. After the cloning of the hormone receptors and the identification of their target sequences on DNA at the end of the 1980s, the question of how steroid hormones modulate the activity of various genes in target cells seemed to be solved. It was clear that steroid hormone receptors are ligand-activated transcriptional modulators, which in most cases act through binding to specific sequences on DNA called hormone-responsive elements (HREs) (1). Careful mutational analysis identified a modular structure of the receptors composed of a DNA-binding domain, nuclear localization signals, a ligand-binding domain, and several transactivation domains (2). Interactions of the receptors with components of the basal transcriptional machinery and with sequence-specific transcription factors were assumed to mediate their transcriptional effects. The prevalent opinion was that the mechanism of action of steroid hormones was a closed chapter ready for the textbooks and what remained to be done to complete the picture was merely the collection of details.
Cutaneous Waldenström's macroglobulinemia with “deck-chair” sign treated with cyclophosphamide
Authors: Julien Autier, Marc Buffet, Laure Pinquier, Anne-Isabelle Merlat-Guitard, Agnes Carlotti, Nathalie Franck, Isabelle Gorin, Nicolas Dupin
Journal: Journal of the American Academy of Dermatology (2005)
Adenocarcinoma of the Breast in a Man
Authors: Andrew Birnie, Sandeep Varma
Journal: New England Journal of Medicine (2005)

An 83-year-old man presented with a one-month history of an enlarging lump on his right nipple. It was asymptomatic. Physical examination revealed an 11-mm erythematous, well-circumscribed nodule attached to the right nipple, which had begun to ulcerate in the center (Panel A), and a normal left nipple (Panel B). The nodule was excised with a 5-mm margin. Histologic examination showed an intraductal and invasive ductal adenocarcinoma of the breast, with the cancer invading the nipple from below. The patient underwent a complete mastectomy and axillary-node dissection. No residual carcinoma was found, and all lymph nodes were free of cancer, indicating . . .
Discovery of CD8 T cell epitopes in Merkel cell polyomavirus through combinatorial encoding with MHC multimers
Authors: Rikke Lyngaa, Natasja W Pedersen, David Schrama, Charlotte A Thrue, Özcan Met, Dafina Ibrani, Per thor Straten, Paul Nghiem, Jürgen C Becker, Sine R Hadrup
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Merkel cell carcinoma (MCC) is a highly aggressive skin cancer induced through oncogenic transformation by the Merkel cell polyomavirus (MCPyV). Intratumoral CD8 T cell infiltration and the immunogenic capacity of the host have been strongly correlated to survival in patients with
METABOLIC STUDIES IN PARALYTIC ACUTE ANTERIOR POLIOMYELITIS. IV. EFFECTS OF TESTOSTERONE PROPIONATE AND ESTRADIOL BENZOATE ON CALCIUM, PHOSPHORUS, NITROGEN, CREATINE AND ELECTROLYTE METABOLISM 1
Authors: G. Donald Whedon, Ephraim Shorr, Vincent Toscani, Estelle Stevens
Journal: Journal of Clinical Investigation (1957)

The general plan, procedure, clinical care and diets employed in these studies were outlined in the first paper in this series (1).The present report is based on the data of seven patients (D.A., J.C.
Delivery of postgraduate medical education--who pays?
Authors: A H Crisp
Journal: BMJ (1977)

As the cost of academic postgraduate medical education increases the DHSS may sometimes need to fund established academic posts or sessions within universities, and it must recognise the need for salaried sessional commitments by clinical tutors and encourage universities to integrate them more effectively into regional medical schools. Such activities will otherwise increasingly impose on undergraduate departments teaching demands that are neither practicable nor proper.
Imaging Steps of Lymphatic Metastasis Reveals That Vascular Endothelial Growth Factor-C Increases Metastasis by Increasing Delivery of Cancer Cells to Lymph Nodes: Therapeutic Implications
Authors: Tohru Hoshida, Naohide Isaka, Jeroen Hagendoorn, Emmanuelle di Tomaso, Yen-Lin Chen, Bronislaw Pytowski, Dai Fukumura, Timothy P. Padera, Rakesh K. Jain
Journal: Cancer Research (2006)

Abstract Preclinical and clinical studies positively correlate the expression of vascular endothelial growth factor (VEGF)-C in tumors and the incidence of lymph node metastases. However, how VEGF-C regulates individual steps in the transport of tumor cells from the primary tumor to the draining lymph nodes is poorly understood. Here, we image and quantify these steps in tumors growing in the tip of the mouse ear using intravital microscopy of the draining lymphatic vessels and lymph node, which receives spontaneously shed tumor cells. We show that VEGF-C overexpression in cancer cells induces hyperplasia in peritumor lymphatic vessels and increases the volumetric flow rate in lymphatics at the base of the ear by 40%. The increases in lymph flow rate and peritumor lymphatic surface area enhance the rate of tumor cell delivery to lymph nodes, leading to a 200-fold increase in cancer cell accumulation in the lymph node and a 4-fold increase in lymph node metastasis. In our model, VEGF-C overexpression does not confer any survival or growth advantage on cancer cells. We also show that an anti-VEGF receptor (VEGFR)-3 antibody reduces both lymphatic hyperplasia and the delivery of tumor cells to the draining lymph node, leading to a reduction in lymph node metastasis. However, this treatment is unable to prevent the growth of tumor cells already seeded in lymph nodes. Collectively, our results indicate that VEGF-C facilitates lymphatic metastasis by increasing the delivery of cancer cells to lymph nodes and therapies directed against VEGF-C/VEGFR-3 signaling target the initial steps of lymphatic metastasis. (Cancer Res 2006; 66(16): 8065-75)
The cardiac renin–angiotensin system is responsible for high‐salt diet‐induced left ventricular hypertrophy in mice
Authors: Philippe Le Corvoisier, Christophe Adamy, Lucien Sambin, Bertrand Crozatier, Alain Berdeaux, Jean‐Baptiste Michel, Luc Hittinger, JinBo Su
Journal: European Journal of Heart Failure (2010)
EPIDEMIC OF VIRAL HEPATITIS APPARENTLY SPREAD BY DRINKING WATER AND BY CONTACT
Authors: John D. Farquhar
Journal: JAMA (1952)

There is conclusive evidence that the virus of epidemic hepatitis is present in the stools of infected persons. Whether cross infection results from this source alone, from the urine, and/or from the nasopharyngeal secretions is still debatable. Epidemiological evidence has suggested to some workers that the virus is spread by nasopharyngeal secretions. However, such epidemiological studies have not been supported by studies in volunteers. No sound evidence has been obtained for the presence of the virus in nasopharyngeal secretions or in the urine of patients with epidemic hepatitis.  Earlier work by Findlay and Willcox 1 in Africa suggested the presence of the virus in urine. It has since been suggested by the same workers that this may have resulted from contamination of the urine with infected blood, in cases of schistosomiasis.  Transmission of the epidemic hepatitis virus by the bites of insects and/or by passive transfer through the medium of
Women in Academic Medicine
Authors: Judi Goldstone
Journal: JAMA (1991)

<h3>To the Editor.—</h3> The article by Nickerson et al<sup>1</sup>was certainly encouraging news regarding the plight of women physicians in academia. Unfortunately, Dr Schaller's Commentary<sup>2</sup>embodies the "Woe is me" mentality that continues to be expressed by those who believe instant advancement ought to have been accomplished yesterday. Academia really is no different from any other form of business. Anyone who belongs to a minority in a field for any length of time must always prove that he or she can perform at the top. Women are capable of anything that men are, and this should be proved with time and numbers of women physicians in the field. Women have done well to minimize sexual stereotypes—we don't think that every time a man and woman converse, they are to be suspected of monkey business. With regard to childbearing and child raising, it is unfair to say that a
Cardiovascular Surveys in Areas with Different Water Supplies
Authors: P. C. Elwood, D. Bainton, F. Moore, D. F. Davies, E. J. Wakley, M. Langman, P. Sweetnam
Journal: BMJ (1971)

Cardiovascular surveys were conducted in areas with different water supplies. In two areas with hard water 243 men were seen and in three areas with soft water 357 men were seen. There was no evidence of an important difference between the two areas in blood pressure, serum cholesterol, blood sugar, or packed cell volume. A variety of measurements were made on an E.C.G. The P-R interval was significantly longer in the men in the hard water area, and a 40-complex trace showed ventricular extrasystoles in a significantly higher proportion of these men than in those in the soft water area.
[487] PREDICTORS OF HBsAg REDUCTION IN HBsAg- NEGATIVE CHRONIC HEPATITIS B PATIENTS TREATED WITH PEGINTERFERON a-2a (40 kD) ALONE OR IN COMBINATION WITH LAMIVUDINE
Authors: M. Brunette, F. Bonino, F. Moriconi, P. Marcellin, G.K. Lau, P. Farci, C. Yurdaydin, T. Piratvisuth, K. Luo, Y. Wang, S. Hadziyannis, E. Wolf, M. Popescu
Journal: Journal of Hepatology (2007)
Molecular characterization of the humoral responses to Cryptococcus neoformans infection and glucuronoxylomannan-tetanus toxoid conjugate immunization.
Authors: J Mukherjee, A Casadevall, M D Scharff
Journal: The Journal of Experimental Medicine (1993)

The molecular characteristics of the humoral immune response to a serotype A Cryptococcus neoformans infection were compared with the response elicited by a cryptococcal glucuronoxylomannan-tetanus toxoid (GXM-TT) conjugate. Anticryptococcal monoclonal antibodies (mAbs) isolated from both responses have previously been shown to recognize the same antigenic determinant of cryptococcal GXM. Southern blot and sequence analyses indicate that the hybridomas isolated from each response arose from only a few precursor B cells. All the mAbs generated from the infected and GXM-TT conjugate-immunized mice utilize the same VH7183 family member: JH2/JH4, v kappa 5.1, and J kappa 1; mAbs generated by different B cells had complementarity-determining region 3's (CDR3s) composed of seven amino acids with a common sequence motif. Thus, the molecular analysis of these anticryptococcal mAb-producing hybridomas indicated that the response to both cryptococcal infection and conjugate immunization was oligoclonal and highly restricted with regard to immunoglobulin gene utilization. The GXM-TT conjugate primarily stimulated isotype switching and clonal proliferation, and did not result in hybridomas expressing additional immunoglobulin repertoires. The mAbs from both responses had a number of replacement mutations at the 5' end of CDR2 that appear to be the result of antigen-driven selection. Somatic mutation also resulted in altered epitope specificity for one mAb, 13F1. Passive administration of representative mAbs from different clones generated in response to the GXM-TT conjugate prolonged survival of lethally infected mice.