tbuckley/cabot-search huggingface dataset:
Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo
Authors: Suzanne M. McGoldrick, Marie E. Bleakley, Abraham Guerrero, Cameron J. Turtle, Tori N. Yamamoto, Shalini E. Pereira, Colleen S. Delaney, Stanley R. Riddell
Journal: Blood (2013)
Causes of Death in Hemophilia
Authors: Jessica H. Lewis
Journal: JAMA (1970)

To the Editor.—  The causes of death in 28 hemophiliac patients are shown in the Table. During the past 15 years, 310 hemophiliacs were seen in this laboratory and follow-up information was obtained about all except eight. Half of the 28 deaths were clearly disease related, six possibly disease related, and in the remaining eight, hemorrhage played no role. The two patients who died with serum hepatitis are included in the disease-related group as, presumably, the hepatitis virus was transmitted through plasma or fraction therapy.  Bleeding into the retroperitoneal area was the most common cause of death. In six of these patients pain and swelling developed gradually and some treatment was instituted before death. Only two of these were related to known injury. In the last two years five other patients with large retroperitoneal hematomas have been treated vigorously and survived. In these it was found necessary to keep the
Abstract 3770: tRNA-mediated regulation of nutrient-responsive pathways in breast cancer cell
Authors: Le-Nguyen Huynh, Maria Neil, Thangavel Muthusamy, Hiep Luu, Devi Nair, Mette P. Ibba
Journal: Cancer Research (2011)

Abstract Autophagy or macroautophagy plays a crucial role in the survival of metabolic-stressed tumor cells by providing sufficient intracellular nutrients and energy to sustain growth. Cancer cells experiencing nutritional stress take advantage of the autophagic pathway to maintain viability. When cells experience nutritional stress, the activity of the serine/threonine kinase mTOR is downregulated, leading to reduced protein synthesis and subsequently increased autophagy. Under these conditions tRNAs, which are essential components of the protein synthesis machinery, accumulate in the nucleus. Cancer cells are often nutrient-starved, yet they still grow and proliferate, which indicates that sufficient amino acid-charged tRNAs are present in the cytosol to support protein synthesis. Our studies in human fibroblasts have shown that accumulation of tRNA in the nucleus, caused by reduced expression of the tRNA-transporting karyopherin Xpo-t, induces a starvation-like response, i.e. activity of the mTOR1C1 pathway is reduced and autophagy upregulated. Thus, we hypothesize that nuclear accumulation of tRNA signals cellular starvation. In this work, we aim to determine if tRNA accumulation in the nucleus, accomplished by reduced expression of tRNA transporting karyopherin Xpo-t, induces a starvation response in breast cancer cells. Using MDA-MB-231 breast cancer cells as a model system for our in-vitro studies, we have shown significant response to nutrient starvation with regard to autophagy. We are currently analyzing if shRNA-mediated knockdown of Xpo-t in MDA-MB-231 cells triggers a starvation-response. Subsequently, we will determine if starvation in combination with Xpo-t knockdown lead to upregulation of autophagy and reduction of mTOR to such level that induces cancer cell death. Additional studies will be done to examine such response in other breast cancer cells and will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3770. doi:10.1158/1538-7445.AM2011-3770
Red blood cell transfusion need at diagnosis adversely affects survival in primary myelofibrosis—increased serum ferritin or transfusion load does not
Authors: Ayalew Tefferi, Ruben A. Mesa, Animesh Pardanani, Kebede Hussein, Susan Schwager, Curtis A. Hanson, David P. Steensma
Journal: American Journal of Hematology (2009)

Serum ferritin level at diagnosis was available in 185 patients with primary myelofibrosis (PMF); twenty-two (12%) patients had serum ferritin >1,000 ng/mL and 32 (17%) were red blood cell (RBC) transfusion-dependent. As expected, RBC transfusion need and increased serum ferritin displayed strong correlation (P < 0.0001); in addition, the latter but not the former correlated with advanced age (P < 0.0001). During median follow-up of 28 months (range 0.5-231), peak serum ferritin levels exceeded 1,000 ng/mL in 41 (22%) patients. On multivariable analysis that included age as a covariate, RBC transfusion need at diagnosis (P < 0.0001), but not increased serum ferritin or transfusion load, predicted shortened survival. The prognostic relevance of RBC transfusion need was independent of the International Prognostic Scoring System and was also illustrated for leukemia-free survival (P = 0.003). In PMF, the presence of a more severe erythropoietic defect, and not iron overload, has additional adverse prognostic value.
Melatonin and Parkinsonism
Authors: Paul S. Papavasiliou
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Lerner discovered melatonin (<i>N</i>-Acetyl-5-methoxytryptamine)<sup>1</sup>and showed that this pineal hormone can induce sedation in man.<sup>2</sup>This agent antagonizes the darkening of the skin and, therefore, perhaps also some other action of melanophore-stimulating hormone (βMSH).<sup>3</sup>Since injections of βMSH had aggravated the tremor of parkinsonism,<sup>4</sup>we had administered this antagonist of βMSH to a patient but induced only a diminution of tremor.<sup>3</sup>Others, however, reported impressive improvement of several symptoms of parkinsonism<sup>5</sup>at a time when we had reversed the adventitious movements caused by levodopa [3-(3, 4-dihydroxyphenyl)-L-alanine] with melatonin in experimental animals.<sup>6</sup>We conducted therefore a single-blind study in patients with parkinsonism who received either melatonin alone or melatonin plus levodopa, which had caused intermittent adventitious movements.<sup>7</sup> The inpatients listed in the Table and all of the outpatients had idiopathic parkinsonism except patient 11 who had postencephalitic disease. Among
Surgical Relief of Aortic Insufficiency by Direct Operation on the Aortic Valve
Authors: WILLIAM H. MULLER, W. DEAN WARREN, J. FRANCIS DAMMANN, JULIAN R. BECKWITH, J. EDWIN WOOD
Journal: Circulation (1960)

The natural history of patients with aortic insufficiency and the previous experimental and clinical operations devised for its relief are reviewed. Methods that have been used at the University of Virginia Hospital for treatment of aortic insufficiency are reported. These procedures include the release of the fixed valve leaflet and removal of calcium from it, aortic valve leaflet extension with suture of a small piece of compressed polyvinyl sponge or Teflon fabric to the edge of one of the leaflets, excision and replacement of a portion of the valve with a synthetic leaflet, and complete subcoronary replacement of the valve with a prosthesis. To relieve isolated rheumatic aortic insufficiency, an annulus has been constricted or a bicuspid aortic valve has been created. Insufficiency resulting from perforation of one or more valve leaflets by subacute bacterial endocarditis has been treated by closure of the perforations. Nineteen patients underwent 21 operations for the correction of aortic insufficiency. All had been in, or were in, heart failure, and several had significant coronary artery disease or multivalvular disease. Eleven of the 19 patients are well or markedly improved. Eight died during or after the operative procedure. It is concluded that a direct attack upon the insufficient aortic valve is the procedure of choice at the present time.
Rheumatoid Arthritis, Spontaneous Remission, And Hypnotherapy
Authors: Forrest J. Cioppa
Journal: JAMA (1974)

To the Editor.—  The factors that induce spontaneous remission are unknown; some may not be measurable. Since the probability of spontaneous remission is invariably invoked when a patient's condition improves after recourse to an unorthodox healing method, it would appear to be of some importance to understand what weight should be consigned to suggestion as a variable among the many factors that contribute to the healing process.  A 10-year-old girl in whom a rheumatologist diagnosed juvenile rheumatoid arthritis responded minimally to large doses of salicylates and physical therapy over a period of seven weeks. She was depressed, uncommunicative, and inactive. When salicylism appeared imminent and corticosteroid therapy was being considered, hypnotherapy was tried. Three sessions were given. Despite resistance to the first session, the patient gave a positive ideomotor response to the question, Does some part of your mind know why you have arthritis? This query induced some anxiety, as
Principles and Management of Surgical Infections
Authors: Jerry D. Smilack
Journal: JAMA (1991)

The dawn of the antibiotic era a half century ago raised hope for the elimination of infections in medical and surgical practice. Yes, countless lives have been saved, and much suffering has been reduced, but only one infection has been eliminated from the world (smallpox, as a result of a massive immunization program). There is no doubt, however, that today's physicians are practicing a style of medicine and surgery nearly unrecognizable from that of their predecessors. Aside from changes resulting from such "high-tech" advances as laser, stereotactic, and transplant surgery, much of the credit for surgical wonders we now take for granted must go to improved understanding of the host immune response, enhanced ability to diagnose and treat diseases, and availability of numerous potent antimicrobial agents. We are at the threshold of monoclonal antibody treatment of sepsis and a number of vaccines previously undreamed of. "... much of the credit for
Effects of the Valsalva maneuver on myocardial ischemia in patients with coronary artery disease.
Authors: C J Pepine, L Wiener
Journal: Circulation (1979)

The influence of the Valsalva maneuver (VM) on myocardial ischemia was evaluated in 24 patients with coronary heart disease. Clinical and hemodynamic responses to the VM were studied during acute ischemia manifested by angina pectoris with transient left ventricular (LV) dysfunction and compared with responses during nonischemic intervals. In the absence of evidence for acute ischemia (angina and increased LV end-diastolic pressure), six patients had abnormal hemodynamic responses to the VM. Five had lack of systolic pressure overshoot and in one, systolic pressure did not decline during straining. When the VM was performed during an ischemic episode, 14 patients had abnormal responses (12 with lack of overshoot in phase IV and two with lack of systolic pressure decline in phase II). In 18 patients a prompt decline in LV end-diastolic pressure occurred with the disappearance of angina during the VM. These changes uniformly occurred during the latter part of straining (VM phase II) as cardiac size and systolic pressure declined. No adverse effects occurred when a VM was performed during acute ischemia. Our observations suggest that the VM abruptly reduces determinants of cardiac oxygen demand, relieving acute ischemia without harmful effects.
Abstract 4080: Global changes in gene expression during phorbol ester-induced differentiation of human acute myeloid leukemia cells
Authors: Emily Swain, Adnan Solaiman, Senaka Ratnayake, Abby Larson, Ryan Deeds, Amy Conner, Jeffrey Forrester, Michael Roberts
Journal: Cancer Research (2010)

Abstract This study seeks to elucidate the molecular mechanisms by which the acute myeloid leukemia cell line, HL-60, is induced to differentiate into macrophage-like cells following exposure to phorbol 12-myristate 13-acetate (PMA). Changes in gene expression over the time course of PMA treatment were measured by DNA microarray analysis and select genes shown to be significantly up- and down-regulated were validated by quantitative, real-time PCR. Functional studies of transcription factor binding activities were performed by the electrophoretic mobility shift assay (EMSA). Novel findings include the rapid and sustained induction of mRNA levels for a group of CC chemokine genes (CCL2, CCL3, CCL3L1, CCL4, CCL4L1 and CCL4L2). These genes displayed 10 to 50-fold expression level increases that were observed within 3 hours of treatment and were maintained through 6 hours post-induction. The anti-proliferative effects of these peptides are being examined on a variety of leukemia cell lines. Among the most highly induced early genes were others known to encode inflammatory response proteins (TNF, IL8, C3AR1). In addition, the transcription factor profile is dramatically altered early in the differentiation time course, with the predicted activation of AP-1 family members (JUNB, FOSL1) and the concomitant inhibition of NFKB (TNFAIP3, NFKBIA, NFKBID). Other transcription factor genes were transiently up regulated (MAFB, GATA2, ETS2) and c-MYC expression was significantly down regulated and remained low during the differentiation course. Pathway analysis was used to predict gene expression changes occurring later in the differentiation process and was tested by microarray analysis. Early events in the genetic re-programming of HL-60 cells in response to the differentiation inducer PMA includes a massive up-regulation of chemokine genes and alteration of the transcription factor profile. The implication of these gene expression changes will be discussed in the context of differentiation therapies for acute myeloid leukemia. 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 4080.
Language as shaped by the brain; the brain as shaped by development
Authors: Joseph C. Toscano, Lynn K. Perry, Kathryn L. Mueller, Allison F. Bean, Marcus E. Galle, Larissa K. Samuelson
Journal: Behavioral and Brain Sciences (2008)

Abstract Though we agree with their argument that language is shaped by domain-general learning processes, Christiansen &amp; Chater (C&amp;C) neglect to detail how the development of these processes shapes language change. We discuss a number of examples that show how developmental processes at multiple levels and timescales are critical to understanding the origin of domain-general mechanisms that shape language evolution.
General practice records should be kept on CDs
Authors: J. Charlton
Journal: BMJ (1996)

EDITOR,—Ian N Purves fails to address some important points in his editorial on the paperless general practice.1

Firstly, how many of the practices that are now paperless have transferred all of their patients' old records to computer?

Secondly, how are records to be transferred from one practice to another when several different computer systems exist and the family health services authorities and health authorities must physically have the medical record envelope and its contents to effect a transfer?

Thirdly, …
Survivin overexpression alone does not alter megakaryocyte ploidy nor interfere with erythroid/megakaryocytic lineage development in transgenic mice
Authors: Donald J. McCrann, Todd Yezefski, Hao G. Nguyen, Nicholas Papadantonakis, Hui Liu, Qiang Wen, John D. Crispino, Katya Ravid
Journal: Blood (2008)
NF- B1 and NF- B2 regulate susceptibility to DNA damage induced intestinal epithelial apoptosis in vivo
Authors: A. Hanedi, C. A. Duckworth, M. D. Burkitt, J. H. Caamano, D. M. Pritchard
Journal: Gut (2011)

<h3>Introduction</h3> The five members of the Nuclear Factor kappa B (NFκB) family of transcription factors signal via two pathways (classical and alternative) and play crucial roles in regulating gastrointestinal inflammation and carcinogenesis. Several mechanisms are likely to be involved including modulation of the key cellular processes of proliferation and apoptosis. NFκB1 has previously been shown to regulate radiation-induced apoptosis in the murine small intestine, but the involvement of other family members, particularly those involved in alternative pathway signalling, in regulating gastrointestinal epithelial apoptosis and proliferation has not previously been investigated. <h3>Methods</h3> Apoptosis was induced in groups of 6 male 10–12 weeks old c-Rel-null, NFκB1(p50)-null and NFκB2(p52)-null mice and their wild-type (C57BL/6) counterparts by two DNA damage inducing stimuli, namely 8Gy γ-irradiation and a single 250 mg/kg intraperitoneal injection of the chemotherapeutic drug Irinotecan. H and E sections were prepared from formalin fixed small intestine and distal half of the colon and cell number, apoptosis and mitosis were assessed on a cell positional basis. <h3>Results</h3> Significant increases in crypt cell number were observed in NFκB1-null and NFκB2-null small intestine and in NFκB1-null and c-Rel-null colon. No significant differences were observed in baseline small intestinal and colonic crypt mitosis between any strains of mice. However, NFκB2-null mice demonstrated a significant increase in spontaneous small intestinal crypt apoptosis. In addition, small intestinal and colonic crypt apoptosis were both significantly increased (up to 3-fold) in NFκB1-null and NFκB2-null mice at 4.5 h following 8Gy γ-irradiation and 6 h following 250 mg/kg Irinotecan relative to wild-type and c-Rel-null mice. Although mitosis was suppressed in the small intestinal and colonic crypts of all strains of mice following DNA damaging stimuli, this suppression occurred to a significantly greater extent in the colonic crypts of NFκB1-null and NFκB2-null mice compared to C57BL/6 mice following Irinotecan treatment. <h3>Conclusion</h3> Individual members of the NFκB family of proteins therefore play specific roles in regulating crypt cell number, apoptosis and mitosis in murine intestinal epithelia. Whereas c-Rel appears to play only a minor role in regulating these processes, disruption of the classical and alternative signalling pathways by deletion of NFκB1 and NFκB2, respectively both increased susceptibility to apoptosis and suppression of mitosis. NFκB1 and NFκB2 may therefore play important roles in regulating inflammatory and neoplastic disease development in intestinal epithelia.
Psychiatry in General Practice — Some Aspects of Fear
Authors: G. Burnham Beaman
Journal: New England Journal of Medicine (1950)

AMONG general practitioners many "old-timers" have intuitively done magnificent work with their nervous patients, whereas many others in younger generations have often felt baffled by psychiatric problems. For a better understanding, some aspects of fear, as it occurs in the doctor no less than it arises to plague everybody else, including psychiatrists, should be considered: what it is, how it may operate to handicap one's practice of medicine, how it may be dealt with in a patient and how knowledge of it makes for better management of psychiatric cases.Throughout all human history the story of mental disease is stark . . .
The Human Interleukin-2 Receptor: Normal and Abnormal Expression in T Cells and in Leukemias Induced by the Human T-Lymphotropic Retroviruses
Authors: WARNER C. GREENE
Journal: Annals of Internal Medicine (1986)

The human receptor for interleukin-2 (T-cell growth factor) plays a critical role in the growth of T cells and is required for full expression of the normal immune response. Through hybridoma and recombinant DNA techniques, the interleukin-2 receptor protein has been biochemically characterized and purified; full-length copies of its complementary DNA have been molecularly cloned, sequenced, and expressed in eukaryotic cells; and the receptor gene has been characterized. Transient expression of the interleukin-2 receptor gene occurs during normal T-cell activation, and high- and low-affinity forms of the membrane receptor exist. A naturally occurring, soluble receptor has also been isolated, and its levels in serum correlate with the activity of various diseases. Deregulation of interleukin-2 receptor expression occurs in T-cell leukemias produced by the human T-lymphotropic retroviruses types I and II (HTLV-I and -II) and has been causally linked to the action of the trans-activator (taf) gene of these viruses. Monoclonal antibodies specific for the interleukin-2 receptor are being evaluated in the treatment of HTLV-I-induced leukemias and other conditions involving the inappropriate function of activated T cells.
Extent of misclassification of death from Creutzfeldt-Jakob disease in England 1979-96: retrospective examination of clinical records
Authors: A. Majeed
Journal: BMJ (2000)

To investigate the extent to which deaths from Creutzfeldt-Jakob disease were misclassified during 1979-96.Structured review of clinical records based on predetermined criteria to determine whether death could have been due to sporadic or variant Creutzfeldt-Jakob disease.100 health authorities and 275 NHS trusts in England.1485 people who died aged 15-44 years from selected neurological disorders in England during 1979-96.Cause of death.The clinical records of 705 (48%) subjects were successfully traced. Tracing of clinical records was highest in subjects who died during 1990-6. There was sufficient information in the records of 640 (91%) of the 705 subjects to exclude Creutzfeldt-Jakob disease as a cause of death. In 61 (9%) subjects, there was insufficient information to reach any conclusion about the validity of the cause of death recorded on the death certificate. The clinical records of four subjects were examined further by the National Creutzfeldt-Jakob Disease Surveillance Unit; none was thought to have died from Creutzfeldt-Jakob disease.No new cases of sporadic or variant Creutzfeldt-Jakob disease were detected in a sample of deaths most likely to have included misclassified cases. This suggests that the surveillance system is unlikely to have missed a significant number of cases among people aged 15-44 years. Hence, any rapid increase in the number of cases of variant Creutzfeldt-Jakob disease in this age group is likely to be real not artefactual.
Telemonitoring did not reduce hospitalizations or ED visits in high-risk elderly patients
Authors: William J. Hall
Journal: Annals of Internal Medicine (2012)

Source Citation Takahashi PY, Pecina JL, Upatising B, et al. A randomized controlled trial of telemonitoring in older adults with multiple health issues to prevent hospitalizations and emergency department visits. Arch Intern Med. 2012 28;172:773-9. 22507696
Ambulatory electrocardiographic records in patients with transient cerebral attacks or palpitation.
Authors: A D Goldberg, E B Raftery, P M Cashman
Journal: BMJ (1975)

Continuous electrocardiographic (ECG) records were made over 24 hours in 130 ambulant outpatients complaining of syncope, dizzy turns, or palpitation. In all these patients resting ECGs had failed to show significant dysrhythmias. Exercise testing was performed on 64 patients and also failed to reveal any dysrhythmias. Analysis of the tape recordings, however, showed appreciable dysrhythmias in 74% of the group. In most cases the dysrhythmias were complex mixtures of rapid supraventricular and ventricular rhythms. bouts of ventricular tachycardia were seen in seven patients, all of whom were women. Episodic complete heart block was seen in only two patients, but prolonged ventricular gaps (greater than 1-5 s), not associated with ectopic beats, were found in 26. No episodes of ventricular fibrillation were recorded. We conclude that many patients with vague symptoms suggestive of transient cerebral ischaemia or irregular heart action have significant and often dangerous dysrhythmias which can be diagnosed only by long-term recording of the ECG under fully ambulant conditions.