tbuckley/cabot-search huggingface dataset:
Cyr61 Mediates Hepatocyte Growth Factor–Dependent Tumor Cell Growth, Migration, and Akt Activation
Authors: C. Rory Goodwin, Bachchu Lal, Xin Zhou, Sandra Ho, Shuli Xia, Alexandra Taeger, Jamie Murray, John Laterra
Journal: Cancer Research (2010)

Abstract Certain tumor cell responses to the growth factor–inducible early response gene product CCN1/Cyr61 overlap with those induced by the hepatocyte growth factor (HGF)/c-Met signaling pathway. In this study, we investigate if Cyr61 is a downstream effector of HGF/c-Met pathway activation in human glioma cells. A semiquantitative immunohistochemical analysis of 112 human glioma and normal brain specimens showed that levels of tumor-associated Cyr61 protein correlate with tumor grade (P &amp;lt; 0.001) and with c-Met protein expression (r2 = 0.4791, P &amp;lt; 0.0001). Purified HGF rapidly upregulated Cyr61 mRNA (peak at 30 minutes) and protein expression (peak at 2 hours) in HGF−/c-Met+ human glioma cell lines via a transcription- and translation-dependent mechanism. Conversely, HGF/c-Met pathway inhibitors reduced Cyr61 expression in HGF+/c-Met+ human glioma cell lines in vitro and in HGF+/c-Met+ glioma xenografts. Targeting Cyr61 expression with small interfering RNA (siRNA) inhibited HGF-induced cell migration (P &amp;lt; 0.01) and cell growth (P &amp;lt; 0.001) in vitro. The effect of Cyr61 on HGF-induced Akt pathway activation was also examined. Cyr61 siRNA had no effect on the early phase of HGF-induced Akt phosphorylation (Ser473) 30 minutes after stimulation with HGF. Cyr61 siRNA inhibited a second phase of Akt phosphorylation measured 12 hours after cell stimulation with HGF and also inhibited HGF-induced phosphorylation of the Akt target glycogen synthase kinase 3α. We treated preestablished subcutaneous glioma xenografts with Cyr61 siRNA or control siRNA by direct intratumoral delivery. Cyr61 siRNA inhibited Cyr61 expression and glioma xenograft growth by up to 40% in a dose-dependent manner (P &amp;lt; 0.05). These results identify a Cyr61-dependent pathway by which c-Met activation mediates cell growth, cell migration, and long-lasting signaling events in glioma cell lines and possibly astroglial malignancies. Cancer Res; 70(7); 2932–41
Fas-mediated apoptosis is important in regulating cell replication and death in trisomy 8 hematopoietic cells but not in cells with other cytogenetic abnormalities
Authors: Elaine M. Sloand, Sonnie Kim, Monika Fuhrer, Antonio M. Risitano, Ryotaro Nakamura, Jaroslaw P. Maciejewski, A. John Barrett, Neal S. Young
Journal: Blood (2002)
COMBINED OXYGEN AND NITROGEN COMPRESSION IN EARLY LUNG HEMORRHAGE
Authors: L. S. MACE
Journal: JAMA (1913)

Since the operation of lung compression with nitrogen gas has become a recognized method of dealing with certain conditions encountered in tuberculosis, we are beginning to realize that this procedure, with some modifications, is applicable to other phases of this disease besides advanced and progressing one-sided lesions. Hemorrhage from the lungs as the first recognized symptom of a lung tuberculosis is common. Hemorrhage is also common as a serious complication in early cases already under treatment. In either case rest is the most important therapeutic measure and the procedure of resting the diseased lung by compression is so rational, and experience with its use in more advanced cases has been so satisfactory, that there is no doubt that this method of treatment is destined to come into more general use in dealing with early cases, particularly early cases complicated by hemorrhage. The conditions whichent themselves in these early ease ecases differ essentially from
The ARH adaptor protein regulates endocytosis of the ROMK potassium secretory channel in mouse kidney
Authors: Liang Fang, Rita Garuti, Bo-Young Kim, James B. Wade, Paul A. Welling
Journal: Journal of Clinical Investigation (2009)

Renal outer medullary potassium (ROMK) channels are exquisitely regulated to adjust renal potassium excretion and maintain potassium balance. Clathrin-dependent endocytosis plays a critical role, limiting urinary potassium loss in potassium deficiency. In renal disease, aberrant ROMK endocytosis may contribute to potassium retention and hyperkalemia. Previous work has indicated that ROMK endocytosis is stimulated by with-no-lysine (WNK) kinases, but the endocytotic signal and the internalization machinery have not been defined. Here, we found that ROMK bound directly to the clathrin adaptor molecule autosomal recessive hypercholesterolemia (ARH), and this interaction was mediated by what we believe to be a novel variant of the canonical "NPXY" endocytotic signal, YxNPxFV. ARH recruits ROMK to clathrin-coated pits for constitutive and WNK1-stimuated endocytosis, and ARH knockdown decreased basal rates of ROMK endocytosis, in a heterologous expression system, COS-7 cells. We found that ARH was predominantly expressed in the distal nephron where it coimmunoprecipitated and colocalized with ROMK. In mice, the abundance of kidney ARH protein was modulated by dietary potassium and inversely correlated with changes in ROMK. Furthermore, ARH-knockout mice exhibited an altered ROMK response to potassium intake. These data suggest that ARH marks ROMK for clathrin-dependent endocytosis, in concert with the demands of potassium homeostasis.
Growth Failure, Deprivation, And Undereating
Authors: Robert G. Thompson
Journal: JAMA (1970)

To the Editor.—  The study by Whitten et al ( 209: 1675, 1969) was well conceived and well executed. However, the choice of the title, Evidence That Growth Failure From Maternal Deprivation Is Secondary to Undereating, and the conclusions reached are not justified from the data provided for the following reasons.  Previous reports dealing with maternal deprivation have described a group of a different age range. Powell et al 1 described a group ranging in age from 3.3 to 11.5 years while Silver et al 2 reported patients ranging from 4 to 16 years. This is in contrast to the patients studied who ranged from 3 1/2 to 23 months.  The patients in this report also show more weight retardation than in previous studies. The patients reported by Whitten et al had weights which averaged 25% less than expected for height while a series of 22 of our patients 3 have
Inhibition of hepcidin transcription by growth factors
Authors: Julia B. Goodnough, Emilio Ramos, Elizabeta Nemeth, Tomas Ganz
Journal: Hepatology (2012)

The hepatic peptide hormone hepcidin controls the duodenal absorption of iron, its storage, and its systemic distribution. Hepcidin production is often insufficient in chronic hepatitis C and alcoholic liver disease, leading to hyperabsorption of iron and its accumulation in the liver. Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) mediate hepatic regeneration after liver injury. We examined the effect of these growth factors on hepcidin synthesis by hepatocytes. HGF and EGF treatment of primary mouse hepatocytes, as well as EGF administration in mice, suppressed hepcidin messenger RNA (mRNA) synthesis. The suppression of hepcidin by these growth factors was transcriptional, and was mediated by a direct effect of HGF and EGF on the bone morphogenetic protein (BMP) pathway regulating hepcidin synthesis. We further show that growth factors interfered with nuclear localization of activated sons of mothers against decapentaplegic (Smad) and increased the nuclear pool of the BMP transcriptional corepressor TG-interacting factor (TGIF). In a kinase screen with small-molecule kinase inhibitors, inhibitors in the PI3 kinase pathway and in the mitogen-activated ERK kinase/extracellular signal-regulated kinase (MEK/ERK) pathway prevented HGF suppression of hepcidin in primary mouse hepatocytes. Conclusion: HGF and EGF suppress hepatic hepcidin synthesis, in part through PI3 kinase MEK/ERK kinase pathways which may be modulating the nuclear localization of BMP pathway transcriptional regulators including activated Smads1/5/8 and the corepressor TGIF. EGF, HGF, and possibly other growth factors that activate similar pathways may contribute to hepcidin suppression in chronic liver diseases, promote iron accumulation in the liver, and exacerbate the destructive disease processes. (HEPATOLOGY 2012;56:291–299)
Clinical Lecture on the Treatment of Compound Depressei Fractures of the Skull
Authors: S. Gamgee
Journal: BMJ (1876)

Association, though much remains st'il to be accomplished in this department.In representations made at various times to the Army and Navy Boards, with respect to the unfavourable position in which the rules of these services place the medical officers; in suggestions as to the com- pulsory Vaccination Bill, the Artisans' Dwellings Bill, the possible provisions for the Care of Habitual Drunkards, for Provident Dispensaries and the medical relief of the sick poor, and for the social and morl improvement of the-medical profession at large, we have only to look at the annual records of the transactions, as published in the JOURNAL, to become aware of the earnest desire of the Association to accomplish measures -which have for their object at once the good of the profession and the service of the public.It is right also to allude to two other matters connected wvith the Association.One of these is the appropriation of a portion of its funds annually to the granting of sums of money in encouragement of scientific inquiries in connection with medicine, for Which £i65,was dispensed during the past year.The other is the Benevolent Fund, raised by voluntary sulbscription, for the temporary relief of distressed medical men, their widows and orphans, and the management of whlich has, since 1835, been a part of the business of the Association.The relief is confined to the cases of regularly educated medical men of irreproachable character, who are in actual distress.The income of the fund, which was for some time small, rose in 1853 to £655, and has been fully maintained since that time.
Book Review The Health Impact of Smoking and Obesity and What to Do about It By Hans Krueger, Dan Williams, Barbara Kaminsky, and David McLean. 374 pp., illustrated. Toronto, University of Toronto Press, 2007. $65 (cloth); $29.95 (paper). 978-0-8020-9200-7 (cloth); 978-0-8020-9441-4 (paper).
Authors: David F. Williamson
Journal: New England Journal of Medicine (2007)
Night‐time sedating H <sub>1</sub> ‐antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial
Authors: M. Staevska, M. Gugutkova, C. Lazarova, T. Kralimarkova, V. Dimitrov, T. Zuberbier, M.K. Church, T.A. Popov
Journal: British Journal of Dermatology (2014)

Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1 -antihistamine in the morning and a sedating first-generation H1 -antihistamine, usually hydroxyzine, at night to enhance sleep. But is this belief well founded?To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria (CSU) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night (levocetirizine plus hydroxyzine) vs. levocetirizine 20 mg daily (levocetirizine monotherapy).In this randomized, double-blind, cross-over study, 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each. At the end of each treatment period, assessments were made of quality of life (Chronic Urticaria Quality of Life Questionnaire, CU-Q2 oL), severity of urticaria symptoms (Urticaria Activity Score, UAS), sleep disturbance during the night and daytime somnolence.Both treatments significantly decreased UAS, night-time sleep disturbances and CU-Q2 oL scores (P < 0·001) without significant differences between the two. Compared with baseline, daytime somnolence was significantly reduced by levocetirizine monotherapy (P = 0·006) but not by levocetirizine plus hydroxyzine (P = 0·218). Direct comparison of the two treatment modalities in terms of daytime somnolence favoured levocetirizine monotherapy (P = 0·026).The widespread belief that sleep is aided by the addition of a sedating first-generation H1 -antihistamine, usually hydroxyzine, at night is not supported. These results are in line with the urticaria guidelines, which state that first-line treatment for urticaria should be new-generation, nonsedating H1 -antihistamines only.
Protein C resistance in severe peripheral atherosclerosis and in unheralded myocardial infarction
Authors: Felicita Andreotti, Raimondo De Cristofano, Giuseppe Patti, Carol C. Shoulders, Sarah E. White, Mary Gilligan, Willy van de Greef, Anne Bradshaw, Graham J. Davies, Attilio Maseri
Journal: Journal of the American College of Cardiology (1996)
Sailing makes use of tobacco sponsorship
Authors: H M White
Journal: BMJ (1997)

<h3>ABSTRACT</h3> The COVID-19 pandemic underlines the need for versatile diagnostic strategies. Here, we have designed and developed toehold RNA-based sensors for direct and ultrasensitive SARS-CoV-2 RNA detection. In our assay, isothermal amplification of a fragment of SARS-CoV-2 RNA coupled with activation of our biosensors leads to a conformational switch in the sensor. This leads to translation of a reporter-protein e.g. LacZ or Nano-lantern that is easily detected using color/luminescence. This response can be visualized by the human eye, or a simple cell phone camera as well as quantified using a spectrophotometer/luminometer. By optimizing RNA-amplification and biosensor-design, we have generated a highly-sensitive diagnostic assay; with sensitivity down to attomolar (100 copies of) SARS-CoV-2 RNA. Finally, this <b>PHA</b>sed <b>N</b>ASBA-<b>T</b>ranslation <b>O</b>ptical <b>M</b>ethod (PHANTOM) efficiently detects the presence of viral RNA in human patient samples, with clear distinction from samples designated negative for the virus. The biosensor response correlates well with Ct values from RT-qPCR tests and thus presents a powerful and easily accessible strategy for detecting Covid infection.
Altered thresholds for thermoregulatory sweating and vasodilatation in anorexia nervosa.
Authors: P Luck, A Wakeling
Journal: BMJ (1980)

The changes in peripheral (hand) blood flow that occurred when deep body temperature was raised were measured in 13 patients with anorexia nervosa and 13 control subjects. The relation between blood flow and core temperature was shifted to the left in the patients with anorexia, with the onset of vasodilatation occurring at lower core and mean skin temperatures: no significant differences in the slopes of the responses were evident. The onset of thermal sweating occurred at lower core and mean skin temperatures in the patients with anorexia than in the controls. After ingestion of a high-energy liquid meal core temperature increased in the patients, and this was accompanied by a significant rise in peripheral blood flow in most cases. A similar meal in the normal subjects was followed by either no change in core temperature or a slight fall, and no consistent change in peripheral blood flow. These findings suggest that the lowering of thresholds for thermoregulatory sweating and vasodilatation may be a contributory factor to the abnormally low core temperature of patients with anorexia and may also explain some of their common complaints relating to feelings of warmth in the hands and feet after meals.
Nonsurgical Treatment of the Primary Tumor in Four Consecutive Cases of Metastasized Colorectal Carcinoma
Authors: D. Baumhoer, T. Armbrust, G. Ramadori
Journal: Endoscopy (2005)

Background and Study Aims: Surgical resection of the primary tumor is standard treatment in stage IV colorectal cancer, but palliative surgery is associated with high morbidity and mortality and with uncertain benefit. The wisdom of surgical resection of asymptomatic or oligosymptomatic primary tumors is therefore questionable. By studying a small series of such patients, we aimed to assess whether endoscopic techniques can offer an effective alternative form of nonsurgical palliative treatment for the prevention of local complications caused by a primary colorectal tumor. Patients and Methods: We treated four consecutive patients who had stage IV colorectal cancer by endoscopic tumor debulking, either using a standard polypectomy snare technique alone or by argon plasma coagulation ablation followed by snare debulking of the primary tumor. Results: Palliation was achieved in all patients, demonstrated by regression of the primary tumor and absence of symptoms related to the colonic tumor during the observation period of up to 24 months. No procedure-associated complications were observed and it was possible to commence systemic chemotherapy immediately after the endoscopic treatment in all four patients. Conclusions: We believe that surgical resection of the primary tumor is not appropriate in all patients with stage IV colorectal cancer, and that this form of treatment should be reserved for patients with signs of complete obstruction in whom local ablative procedures are not possible. Simple endoscopic techniques for treatment of the primary tumor, in conjunction with systemic chemotherapy, may be the most suitable form of management for patients with stage IV colorectal tumors.
Atrioventricular block in posterior acute myocardial infarction: a clinicopathologic correlation.
Authors: F J Bilbao, I E Zabalza, J R Vilanova, J Froufe
Journal: Circulation (1987)

The specialized conducting systems of 44 hearts with posterior-inferior acute myocardial infarction were studied to clarify the anatomic basis of atrioventricular (AV) block. The results showed a lack of correlation between the block and the lesional pathology of the specialized conducting system. On the other hand, an evaluation of the atrial prenodal myocardium revealed strong clinicopathologic correlation between the block and the necrotic damage to these fibers. Twenty-nine or 97% of patients with AV block showed acute necrosis of the prenodal atrial myocardium. Considering the conducting prenodal septal atrial myocardium as a suprahisian structure, the necrosis at this level would provide an anatomic basis of the block in posterior-inferior acute myocardial infarction. Analysis of the behavior of the AV block after pharmacologic treatment further established a relationship between the block and acute lesions in the central conduction system.
Current Approaches and Recent Developments in the Management of Head and Neck Paragangliomas
Authors: David Taïeb, Alexandre Kaliski, Carsten C. Boedeker, Victoria Martucci, Tito Fojo, John R. Adler, Karel Pacak
Journal: Endocrine Reviews (2014)

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors belonging to the family of pheochromocytoma/paraganglioma neoplasms. Despite advances in understanding the pathogenesis of these tumors, the growth potential and clinical outcome of individual cases remains largely unpredictable. Over several decades, surgical resection has long been the treatment of choice for HNPGLs. However, increasing experience in various forms of radiosurgery has been reported to result in curative-like outcomes, even for tumors localized in the most inaccessible anatomical areas. The emergence of such new therapies challenges the traditional paradigm for the management of HNPGLs. This review will assist and guide physicians who encounter patients with such tumors, either from a diagnostic or therapeutic standpoint. This review will also particularly emphasize current and emerging knowledge in genetics, imaging, and therapeutic options as well as the health-related quality of life for patients with HNPGLs.
HIGH EXERCISE-INDUCED PLATELET REACTIVITY IN PATIENTS WITH ANDERSON-FABRY'S DISEASE
Authors: Costantino Smaldone, Giancarla Scalone, Antonia Camporeale, Anna Zampetti, Irma Battipaglia, Andrea Macchione, Fulvio Bellocci, Claudio Feliciani, Gaetano A. Lanza, Maurizio Pieroni, Filippo Crea
Journal: Journal of the American College of Cardiology (2011)
Prevalence of respiratory symptoms, bronchial hyperresponsiveness and atopy among adults: west and east Germany
Authors: D Nowak, J Heinrich, R Jorres, G Wassmer, J Berger, E Beck, S Boczor, M Claussen, HE Wichmann, H Magnussen
Journal: European Respiratory Journal (1996)

The prevalence of respiratory symptoms, atopic sensitization and bronchial hyperresponsiveness was compared in a random sample of adults, 20-44 yrs of age, in two cities in West and East Germany, Hamburg and Erfurt, respectively. There were much higher levels of outdoor air pollution due to sulphur dioxide and suspended particulates in Erfurt, and major differences in living conditions during the last 40 yrs. Within the European Respiratory Health Survey, a short questionnaire was answered by 3,156 (80% response rate) subjects in Hamburg and 3,272 (74%) in Erfurt. A subset of responders to the short questionnaire completed a long questionnaire, spirometry, methacholine or bronchodilator test, skin test, and total and specific immunoglobulin E (IgE) measurements, with a total number of 1,159 participants in Hamburg and 731 in Erfurt. Six out of 8 questions on respiratory symptoms and diagnoses were answered in the affirmative more frequently in Hamburg than in Erfurt. In Hamburg, mean forced expiratory volume in one second (FEV1)% of predicted was 105 vs 107% in Erfurt (p &lt; 0.0001), and bronchial hyperresponsiveness was more frequently observed in Hamburg than in Erfurt (25 vs 19%; p &lt; 0.05). Atopic sensitization was more prevalent in Hamburg than in Erfurt regarding the results of skin tests against grass pollen (24 vs 19%; p &lt; 0.05), birch pollen (19 vs 8%; p &lt; 0.0005), cat (10 vs 2%; p &lt; 0.0005), and Dermatophagoides pteronyssinus (14 vs 10%; p &lt; 0.05). This was reflected by the prevalences of positive specific IgE values, which were higher in Hamburg than in Erfurt for grass (26 vs 20%; p &lt; 0.05), birch (20 vs 10%; p &lt; 0.0005) and cat (12 vs 8%; p &lt; 0.05). In Hamburg, compared to Erfurt, there was: a lower mean number of siblings (p &lt; 0.005); a higher degree of childhood and current exposure to environmental tobacco smoke (p &lt; 0.005); and a higher frequency of fitted carpets and reported mould or mildew inside the house (p &lt; 0.005). Therefore, these data may support the hypothesis that childhood factors and exposure to indoor allergens and irritants may have been more relevant for the development of asthma and atopy than the potential long-term exposure to high concentrations of sulphur dioxide and particulate matter.