tbuckley/cabot-search huggingface dataset:
Abstract 5200: Role of MLK3 in breast cancer cell migration and metastasis
Authors: Gautam Sondarva, Suneet Mehrotra, Rajakishore Mishra, Velusamy Rangasamy, Jawed Fareed, Basabi Rana, Ajay Rana
Journal: Cancer Research (2010)

Abstract Effectively treating breast cancer metastasis is one of the biggest challenges in breast cancer therapy. The overall poor prognosis associated with cancer cell migration to distal organs underscores the critical need to understand the biology of the disease in order to develop more effective therapies. Members of protein kinase family have often been targeted for therapeutic purposes in different types of cancer, including breast cancer, and several protein kinase inhibitors are currently in clinical trials for specific types of cancer. The members of Mixed Lineage Kinases (MLKs) are novel family of MAP3Ks and their physiological function is not known, however, we and others have shown that several of MLK family members activate Jun- N-terminal Kinases (JNKs) and MLK activation regulates survival in neuronal cells. Recently, we have seen that MLK3 is highly expressed in invasive breast cancer cell lines and in primary breast tumors, compared to the normal mammary tissue from same patient. Since MLK3 was initially identified from platelet cell line, CMK11-5, and association of venous thrombosis and occult cancer was recognized almost 140 years ago, we hypothesized that MLK3 or other MLKs are important in proteinase receptor-mediated signaling. Furthermore, the downstream effectors of proteinase receptors (PARs) that mediate the breast cancer cell growth, migration and metastasis to distal organs are currently unknown. We examined the role of MLK3 in thrombin mediated signaling in a highly invasive breast cancer cell line, MDA-MB-231. Thrombin treatment of these cells activated MLK3 kinase in a time dependent manner. MLK3 was activated within 2 minutes of thrombin treatment and the activity peaked at 5 minutes, and was associated with consequent activation of its downstream target JNK. Furthermore, pretreatment of MDA-MB-231 with an MLK inhibitor, CEP-11004 completely blocked thrombin-induced JNK activation. Importantly, we also discovered that thrombin induces MLK-dependent migration in MDA-MB-231 cell line was blocked by MLKs inhibitor, CEP-11004. These results collectively suggest that MLK3 is an important target of proteinase receptors-mediated migration/invasion/metastatic pathways, and help us to identify MLK family members’ inhibitors as viable drugs to treat metastatic breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5200.
Is the illusion of conscious will an illusion?
Authors: Robert J. Sternberg
Journal: Behavioral and Brain Sciences (2004)

This book is a tour de force in showing that what we believe to be actions dictated by conscious will are not, in fact, wholly dictated by conscious will. However, Wegner has fallen into the trap of making claims that go beyond his data to make his case more compelling and newsworthy. Psychology needs to be informed by common sense.
Autoimmune hemolytic anemia in patients infected with human immunodeficiency virus‐1
Authors: Prasad Rao Koduri, Prema Singa, Petros Nikolinakos
Journal: American Journal of Hematology (2002)

Abstract Four men were diagnosed with advanced human immunodeficiency virus infection (AIDS) and autoimmune hemolytic anemia (HIV‐AIHA) during the years 1997–2000 at Cook County Hospital, Chicago. All patients presented with the acute onset of severe hemolytic anemia, fever, and splenomegaly. The direct and indirect antiglobulin tests were positive in all, and three patients had mixed warm and cold autoantibody hemolytic anemia. Shortly after admission, two patients died of severe anemia. Two patients responded to prednisone therapy and remain in remission from AIHA for 15 and 30 months, respectively. Am. J. Hematol. 70:174–176, 2002.© 2002 Wiley‐Liss, Inc.
YB-1 Bridges Neural Stem Cells and Brain Tumor–Initiating Cells via Its Roles in Differentiation and Cell Growth
Authors: Abbas Fotovati, Samah Abu-Ali, Pei-Shan Wang, Loic P. Deleyrolle, Cathy Lee, Joanna Triscott, James Y. Chen, Sonia Franciosi, Yasuhiro Nakamura, Yasuo Sugita, Takeshi Uchiumi, Michihiko Kuwano, Blair R. Leavitt, Sheila K. Singh, Alexa Jury, Chris Jones, Hiroaki Wakimoto, Brent A. Reynolds, Catherine J. Pallen, Sandra E. Dunn
Journal: Cancer Research (2011)

The Y-box binding protein 1 (YB-1) is upregulated in many human malignancies including glioblastoma (GBM). It is also essential for normal brain development, suggesting that YB-1 is part of a neural stem cell (NSC) network. Here, we show that YB-1 was highly expressed in the subventricular zone (SVZ) of mouse fetal brain tissues but not in terminally differentiated primary astrocytes. Conversely, YB-1 knockout mice had reduced Sox-2, nestin, and musashi-1 expression in the SVZ. Although primary murine neurospheres were rich in YB-1, its expression was lost during glial differentiation. Glial tumors often express NSC markers and tend to loose the cellular control that governs differentiation; therefore, we addressed whether YB-1 served a similar role in cancer cells. YB-1, Sox-2, musashi-1, Bmi-1, and nestin are coordinately expressed in SF188 cells and 9/9 GBM patient-derived primary brain tumor-initiating cells (BTIC). Silencing YB-1 with siRNA attenuated the expression of these NSC markers, reduced neurosphere growth, and triggered differentiation via coordinate loss of GSK3-β. Furthermore, differentiation of BTIC with 1% serum or bone morphogenetic protein-4 suppressed YB-1 protein expression. Likewise, YB-1 expression was lost during differentiation of normal human NSCs. Consistent with these observations, YB-1 expression increased with tumor grade (n = 49 cases). YB-1 was also coexpressed with Bmi-1 (Spearmans 0.80, P > 0.001) and Sox-2 (Spearmans 0.66, P > 0.001) based on the analysis of 282 cases of high-grade gliomas. These proteins were highly expressed in 10/15 (67%) of GBM patients that subsequently relapsed. In conclusion, YB-1 correlatively expresses with NSC markers where it functions to promote cell growth and inhibit differentiation.
PICK1 uncoupling from mGluR7a causes absence-like seizures
Authors: Federica Bertaso, Chuansheng Zhang, Astrid Scheschonka, Frédéric de Bock, Pierre Fontanaud, Philippe Marin, Richard L Huganir, Heinrich Betz, Joël Bockaert, Laurent Fagni, Mireille Lerner-Natoli
Journal: Nature Neuroscience (2008)
Ultrasonic Doppler Auscultation of the Heart
Authors: Denis Abelson
Journal: JAMA (1968)

With an ultrasonic fetal heart detector, several low-frequency Doppler signals can be heard over the precordium. In normals, the characteristic pattern comprises atrial (a) ventricular systolic (β), and ventricular diastolic (8) components. During quiet breathing the β signal is usually loudest (β pattern), but on deep inspiration, lying, or squatting, the α signal predominates (α pattern). In atrial flutter or fibrillation the a signal disappears, and in some cases quivering noises (ψ signals) are audible. The Dopplercardiophone can also be useful at the bedside, in conjunction with the stethoscope, in elucidating gallop rhythm. Simultaneous recordings of the Doppler-cardiogram with electrocardiogram and phonocardiogram help to relate the signals to discrete cardiac events. The Doppler signals are probably mainly due to blood flow, movement of the heart wall, or both. The contribution of valve closure is relatively minor.
Decrease in sulphated glycosaminoglycans in aortic dissection--possible role in the pathogenesis
Authors: P. S. Gutierrez, I. C. d. Almeida, H. B Nader, M. d. L. Higuchi, N. Stolf, C. P Dietrich
Journal: Cardiovascular Research (1991)

Journal Article Decrease in sulphated glycosaminoglycans in aortic dissection—possible role in the pathogenesis Get access Paulo Sampaio Gutierrez, Paulo Sampaio Gutierrez Correspondence to: Dr Gutierrez Search for other works by this author on: Oxford Academic PubMed Google Scholar Igor Correia de Almeida, Igor Correia de Almeida Search for other works by this author on: Oxford Academic PubMed Google Scholar Helena B Nader, Helena B Nader Search for other works by this author on: Oxford Academic PubMed Google Scholar Maria de Lourdes Higuchi, Maria de Lourdes Higuchi Search for other works by this author on: Oxford Academic PubMed Google Scholar Noedir Stolf, Noedir Stolf Search for other works by this author on: Oxford Academic PubMed Google Scholar Carl P Dietrich Carl P Dietrich Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 25, Issue 9, September 1991, Pages 742–748, https://doi.org/10.1093/cvr/25.9.742 Published: 01 September 1991 Article history Received: 01 February 1991 Accepted: 16 May 1991 Published: 01 September 1991
Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms
Authors: Ayana Kon, Lee-Yung Shih, Masashi Minamino, Masashi Sanada, Yuichi Shiraishi, Yasunobu Nagata, Kenichi Yoshida, Yusuke Okuno, Masashige Bando, Ryuichiro Nakato, Shumpei Ishikawa, Aiko Sato-Otsubo, Genta Nagae, Aiko Nishimoto, Claudia Haferlach, Daniel Nowak, Yusuke Sato, Tamara Alpermann, Masao Nagasaki, Teppei Shimamura, Hiroko Tanaka, Kenichi Chiba, Ryo Yamamoto, Tomoyuki Yamaguchi, Makoto Otsu, Naoshi Obara, Mamiko Sakata-Yanagimoto, Tsuyoshi Nakamaki, Ken Ishiyama, Florian Nolte, Wolf-Karsten Hofmann, Shuichi Miyawaki, Shigeru Chiba, Hiraku Mori, Hiromitsu Nakauchi, H Phillip Koeffler, Hiroyuki Aburatani, Torsten Haferlach, Katsuhiko Shirahige, Satoru Miyano, Seishi Ogawa
Journal: Nature Genetics (2013)
Changing Face of Medical Practice
Authors: J. Swayne
Journal: BMJ (1970)

SIR,-I regard the conclusions of the Royal Free epidemic (3 January, p. 7) as nonsense.Many of these girls were known to me.Illness was alien to their nature.The course of their illness, fever pattern duration, and sequelae can be explained if one follows the course of some of the increasing viral infec- tions which one encounters in general practice.They get better but not, I fear, through our intervention.Take another look at the Royal Free.I'm sure the adage "what we know we recog- nize" applies here.In the meantime I advise those of us who have to deal with epidemics in institutions: don't be hasty in calling in a psychiatrist, but first read the small print in your chapter on the central nervous system.-I am, etc., B. JUDGE.Birmingham 29.
FACTORS INFLUENCING HEMATOPOIETIC SPLEEN COLONY FORMATION IN IRRADIATED MICE
Authors: Dane R. Boggs, John C. Marsh, Paul A. Chervenick, Carter R. Bishop, George E. Cartwright, Maxwell M. Wintrobe
Journal: The Journal of Experimental Medicine (1967)

Normal dog plasma and serum, human, rat, and Swiss-Webster mouse plasma, phytohemagglutinin, sheep red cells, mumps and influenza vaccine, fibrinogen, and endotoxin injected before irradiation led to an increased number of endogenously derived spleen colonies in irradiated mice. Spleen weight and uptake of radioactive iron and iododeoxyuridine into such spleens were also increased. The relationship between these parameters of splenic hematopoiesis was unchanged by plasma injection suggesting that, while the number of colonies was increased, the composition of individual colonies was unchanged. This conclusion was supported by studies on plethoric mice in which splenic erythropoiesis is abolished. Increased splenic hematopoiesis was accompanied by an increase in the volume of packed red blood cells 10 days after irradiation. The total volume of plasma injected, the number of days of plasma injection preceding irradiation, and the route of administration were all important variables influencing the effect of plasma injections. Crude fractions of human albumin and gamma globulin, cortisol, C57BL (maternal) and DBA (paternal) mouse plasma, and isogeneic plasma were without effect. The ineffectiveness of isogeneic and closely related allogeneic plasma rendered unlikely the hypothesis that this effect represented the presence of homeostatic hematopoietic regulating factors in plasma. The increased hematopoiesis induced with plasma appeared to be limited to the spleen, for increased bone marrow hematopoiesis was not detected. Certain observations suggested that the effect of plasma may not be due to an antigenic or an inflammatory effect. From current observations, it was unclear whether the increased colonies induced by plasma were representative of expansion of the colony-forming cell pool or of increased efficiency of growth of the fraction surviving irradiation.
West Virginia Lobotomy Project
Authors: Walter Freeman
Journal: JAMA (1962)

THIS STUDY of the late results of the transorbital lobotomy project in West Virginia (1952 to 1955) was prompted by the much larger study made in England and Wales, covering 10,365 patients followed up from 3 to 15 years. This monograph is a mine of information concerning the types of patients coming to operation and the long-term results. The present study is more modest, covering 787 patients operated upon by me in 4 of the 5 state mental hospitals in West Virginia, at Huntington, Lakin, Spencer, and Weston. The Barboursville patients were transferred to nearby Huntington for operation and most of them were returned there after a few days. The original report described the methods, after-care, and early follow-up of 602 patients. It showed that 38% of all patients were out of the hospital, and only 21% on "disturbed" wards, as compared with 67% previous to operation. In a roughly
Microdeposition of amyloid in the joints.
Authors: Y A Goffin, Y Thoua, P R Potvliege
Journal: Annals of the Rheumatic Diseases (1981)

The distribution of amyloid in various organs, including the hip and the sternoclavicular joints, was systemically investigated in a prospective necropsy study of 91 unselected individuals whose median age was 70 years. The overall incidence of amyloid microdeposits in both joints was 56%. Their presence correlated significantly with age only. The deposition began earlier in the sternoclavicular joint, where the fibrocartilaginous disc was almost exclusively affected. The myocardium was the next most frequently affected organ, with an incidence of 12.2%. Minor amyloidosis of the articular tissues had no significant clinical counterpart, neither was it associated with any particular disease. It seemingly represents a localised and isolated degenerative phenomenon, whose morphological aspects invite speculation about the pathogenic role of long-lasting mechanical stress.
Role of nitric oxide in parasympathetic modulation of beta-adrenergic myocardial contractility in normal dogs.
Authors: J M Hare, J F Keaney, J L Balligand, J Loscalzo, T W Smith, W S Colucci
Journal: Journal of Clinical Investigation (1995)

In vitro studies indicate that muscarinic cholinergic inhibition of beta-adrenergic cardiac responses may be modulated in part by nitric oxide (NO). To evaluate the role of NO in parasympathetic inhibition of the beta-adrenergic contractile response in vivo, we assessed the inotropic response to dobutamine before and during bilateral vagus nerve stimulation in closed-chest dogs. Dobutamine administration and vagal stimulation were repeated during intracoronary infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 10 mumol/min) and again following infusion of L-arginine (100 mg/kg). In eight dogs, intracoronary dobutamine infusion at rates of 25 and 50 micrograms/min increased peak +dP/dt by 131 +/- 24 and 168 +/- 22%, respectively (P < 0.0001). Vagal stimulation (2.5 Hz) attenuated the responses to dobutamine (25 and 50 micrograms/min) by 23 +/- 4 and 21 +/- 4%, respectively (P < 0.001). L-NMMA reduced (by 44-62%; P < 0.001) and L-arginine restored vagal inhibition of the dobutamine-stimulated inotropic response. In a second group of nine dogs, dobutamine was administered systemically to assure a constant concentration in the coronary circulation. Vagal stimulation (2.5 Hz) attenuated the dobutamine-stimulated inotropic response (2.5 and 5.0 micrograms/kg per min) by 40 +/- 12% and 57 +/- 8%, respectively (P < 0.004). As with intracoronary dobutamine, L-NMMA diminished and L-arginine restored vagal inhibition of the inotropic response to dobutamine. Intracoronary infusion of atropine (12 micrograms/min) abolished the vagal inhibitory effect, and intracoronary infusion of 8-bromo-cyclic GMP (1 and 10 mM) caused a dose-dependent attenuation of the dobutamine-stimulated increase in +dP/dt. These data suggest that NO mediates, at least in part, vagal inhibition of the inotropic response to beta-adrenergic stimulation by dobutamine, and thus may play a role in normal physiologic regulation of myocardial autonomic responses.
SPORADIC TRICHINOSIS WITH EXTREME HYPOTENSION
Authors: Garnett Cheney
Journal: JAMA (1926)

Sixty-six years ago, Zenker was the first to correlate certain symptoms in man with<i>Trichina spiralis</i>infection, and since then many cases have been completely reported both in this country and in Europe. The case here described presents an interesting problem in diagnosis and certain features little recognized as yet in America. <h3>Report of Case</h3> A Filipino cook, aged 25, unmarried, was brought to the hospital complaining of general weakness. He had lived in San Francisco for the past five years and had been well except for influenza seven years previously. Six months before, he was in a hospital following an injury to his head, but he had made a good recovery. Two weeks before entry, he began to feel weak and his legs seemed heavy. His only other complaints were a sharp subxiphoid pain, and a diarrhea the day before admission. He was unable to associate any dietary indiscretions
The Premenstrual Syndromes
Authors: Jane E. Hodgson
Journal: JAMA (1988)

"Premenstrual tension" was first described by Frank in 1931, but truly scientific investigation of this condition, now known as "PMS" ("premenstrual syndrome") has scarcely begun. It remains a poorly defined condition for which we know neither the cause nor the treatment. That women are victimized by their hormones is a common conviction among the laity, who are demanding help for PMS victims from a somewhat bewildered medical profession. Much is currently being written about PMS, and we are witnessing an almost cultlike wave of symposia, lectures, and even videotapes on the topic. If the clinical entity PMS really exists, the legal and economic implications are many. The subject demands and deserves our serious concern. This 157-page volume consists of ten papers presented at a symposium entitled "Premenstrual Syndrome: New Findings and Controversies," recently held at Mount Sinai School of Medicine in New York City. The updated contributions are described by
The LD78β isoform of MIP-1α is the most potent CCR5 agonist and HIV-1–inhibiting chemokine
Authors: Patricia Menten, Sofie Struyf, Evemie Schutyser, Anja Wuyts, Erik De Clercq, Dominique Schols, Paul Proost, Jo Van Damme
Journal: Journal of Clinical Investigation (1999)

LD78α and LD78β are 2 highly related nonallelic genes that code for different isoforms of the human CC chemokine macrophage inflammatory protein-1α (MIP-1α). Two molecular forms of natural LD78β (7.778 and 7.793 kDa) were identified from conditioned media of stimulated peripheral blood mononuclear cells. Although LD78α and LD78β only differ in 3 amino acids, both LD78β variants were 100-fold more potent chemoattractants for mouse lymphocytes than was LD78α. On the contrary, LD78β was only 2-fold more efficient than LD78α in chemoattracting human lymphocytes and monocytes. Using CC chemokine receptor–transfected cells, both molecular forms of LD78β proved to be much more potent than LD78α in inducing an intracellular calcium rise through CCR5. Compared with LD78α and RANTES, this preferential binding of LD78β to CCR5 resulted in a 10- to 50-fold higher potency in inhibiting infection of peripheral blood mononuclear cells by CCR5-using (R5) HIV-1 strains. To date, LD78β is the most potent chemokine for inhibiting HIV-1 infection, and can be considered as a potentially important drug candidate for the treatment of infection with R5 HIV-1 strains.
Hearing Aids for the Elderly
Authors: George E. Shambaugh
Journal: JAMA (1971)

<h3>To the Editor.—</h3> The LETTER (<b>216</b>: 1349, 1971) recommending a tape recorder to talk to hard-of-hearing patients offers a useful method but includes common fallacies. Most elderly patients do not have otosclerosis; if they did, their hearing could be restored through stapes surgery (age is no contraindication) and they would not need amplification. The statement is made that "if the hearing loss is entirely an eighth nerve deafness, the device will not work." Nearly all elderly patients have a nerve-type deafness, but many have good speech discrimination, and they are good candidates for amplification. Fortunately, cases of nerve deafness with poor speech discrimination'are in the minority. Such patients do poorly with amplification, but many of them have bilateral endolymphatic hydrops (Ménière's disease) and, in some, discrimination can be improved by medical treatment. The old-fashioned ear trumpet is still the best means for communicating with elderly hard-of-hearing patients.
Measurement of human serum erythropoietin by erythroid colony‐forming technique using fetal mouse liver cells
Authors: Takahiro Okamoto, Akihisa Kanamaru, Hiroshi Hara, Kiyoyasu Nagai
Journal: American Journal of Hematology (1982)

Abstract A quantitative bioassay for serum erythropoietin in anemic patients was established with erythroid colony‐forming technique using methyl cellulose. Fetal mouse liver contains many erythropoietin‐dependent erythroid colony‐forming cells (CFU‐E) with the concentration as well as sensitivity to erythropoietin being the highest at 13–14 days of gestation. Linearity in the erythropoietin response curve for the number of colonies from CFU‐E in fetal livers of 13–14 days gestation was obtained for erythropoietin concentrations in the culture medium of 3.9 to 125 mU/ml. When newborn liver cells were used instead, the linearity occurred at 31.2 to 250 mU/ml. Measurement of erythropoietin by the erythroid colony‐forming technique for sera from patients with various anemias was compared with that of the assay method using radioiron incorporation into heme in the suspension culture of fetal mouse liver cells. There was a good correlation between the values of both assay methods (r = 0.856, p &lt; 0.001). Also, levels of erythropoietin measured by this assay method showed the expected inverse relationship to the hemoglobin concentration in the sera from the patients.
Effects of a vasopressin antagonist with combined antipressor and antiantidiuretic activities in rats with left ventricular dysfunction.
Authors: R A Mulinari, I Gavras, Y X Wang, R Franco, H Gavras
Journal: Circulation (1990)

These experiments assessed the hemodynamic and aquaretic effects of an arginine vasopressin (AVP) antagonist with dual V1V2-receptor inhibiting properties in rats with congestive heart failure resulting from ischemic cardiomyopathy. The compound d(CH2)5-D-Tyr(Et)VAVP was used in these studies. Rats with limited or extensive myocardial infarcts (i.e., with less than 50% or greater than 66% necrosis of the left ventricular wall, respectively, induced by left coronary ligation) and sham-operated controls received the AVP antagonist (100 micrograms/kg i.v.) 4 weeks later. This agent produced an 18% increase in cardiac output (p less than 0.05) and 13% decrease in systemic vascular resistance in the severely damaged rats, both changes being significantly different from those seen in the normal controls or the rats with limited infarcts. All animals exhibited increases in urinary output of 4-10-fold over baseline. We conclude that the hemodynamic and renal effects of this agent are beneficial in animals with left ventricular dysfunction.