tbuckley/cabot-search huggingface dataset:
AN ATYPICAL FIBROLIPOMA OF UNUSUAL SIZE
Authors: J. A. King
Journal: JAMA (1918)

The unusual size and the difficulty of classification of this tumor make the case worthy of report. In April, 1917, A. H., a nearly pure-bred Indian girl, aged 21, presented herself to me for treatment. She was well developed and with all organic functions apparently normal. She gave the history of having been born with a small nodule or induration of the skin immediately below the inguinal region in the left thigh, which soon began to increase in size and extend downward. The entire left thigh was greatly increased in size as compared with the right. The epidermis of the skin covering the external aspect and the outer half of the posterior and anterior aspects was apparently normal, but the deeper layers of the skin were very much thickened and indurated and seemed to be continuous with the subcutaneous tissue; but beginning at the middle of the anterior and posterior
VCAM-1 Promotes Osteolytic Expansion of Indolent Bone Micrometastasis of Breast Cancer by Engaging α4β1-Positive Osteoclast Progenitors
Authors: Xin Lu, Euphemia Mu, Yong Wei, Sabine Riethdorf, Qifeng Yang, Min Yuan, Jun Yan, Yuling Hua, Benjamin J. Tiede, Xuemin Lu, Bruce G. Haffty, Klaus Pantel, Joan Massagué, Yibin Kang
Journal: Cancer Cell (2011)
Hemodynamic Alterations of Acute Pulmonary Thromboembolism
Authors: Loren F. Parmley, Robert L. North, Bruce S. Ott
Journal: Circulation Research (1962)

A method is described of producing pulmonary embolism in the dog by the use of various-sized autologous clots made radiopaque. This method of experimental pulmonary embolism results in dilatation of the large- to small-sized pulmonary arteries and a consistent hemodynamic response in the pulmonary circulation, characterized by a marked rise in pulmonary arteriolar resistance with increased pulmonary arterial pressure but persistently normal pulmonary venous and "capillary" pressures. Data are presented to support the concept that the pulmonary hemodynamic changes that result from an initial pulmonary thromboembolism are primarily the result of vasoconstriction of the small pulmonary arteries or arterioles, presumably by a reflex mechanism. Mechanical blockage of the pulmonary vascular bed is considered to be of importance in causing hemodynamic alterations only after massive or repeated pulmonary embolism. The increase in pulmonary arteriolar resistance that results from the vasomotor response to pulmonary embolism is transient, whereas that due to mechanical blockage results in sustained pulmonary hypertension. Systemic arterial pressure does not show a consistent response to pulmonary embolism and could not be related to the hemodynamic alterations that occurred in the pulmonary circulation. Severe systemic hypotension resulted unpredictably but was more frequent after repeated or extensive pulmonary embolism. The systemic hypotensive reaction to pulmonary embolism is only in part due to a decreased cardiac output. The more severe responses are best explained on the basis of a vasomotor reflex producing a decrease in systemic arterial resistance. The two mechanisms of death in this experimental series were severe systemic hypotension with development of fatal ventricular arrhythmias and, almost as frequent, pulmonary edema that was characterized by severe pulmonary hypertension in the presence of a normal pulmonary venous pressure. There are many similarities between the experimental findings of this study and the clinical event of human pulmonary thromboembolism. Attention is drawn to the need for further investigation of the mechanism of the systemic arterial pressure response that often causes death and appears to be independent of the magnitude of the pulmonary hemodynamic changes.
Essential Role of CCR2 in Neutrophil Tissue Infiltration and Multiple Organ Dysfunction in Sepsis
Authors: Fabricio O. Souto, José C. Alves-Filho, Walter M. Turato, Maria Auxiliadora-Martins, Aníbal Basile-Filho, Fernando Q. Cunha
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Sepsis is defined as a systemic inflammatory response to infection, which in its severe form is associated with multiple organ dysfunction syndrome (MODS). The precise mechanisms by which MODS develops remain unclear. Neutrophils have a pivotal role in the defense against infections; however, overwhelming activation of neutrophils is known to elicit tissue damage.We investigated the role of the chemokine receptor CCR2 in driving neutrophil infiltration and eliciting tissue damage in remote organs during sepsis.Sepsis was induced in wild-type mice treated with CCR2 antagonist (RS504393) or CCR2(-/-) mice by cecal ligation and puncture (CLP) model. Neutrophil infiltration into the organs was measured by myeloperoxidase activity and fluorescence-activated cell sorter. CCR2 expression and chemotaxis were determined in neutrophils stimulated with Toll-like receptor agonists or isolated from septic mice and patients.CCR2 expression and responsiveness to its ligands was induced in circulating neutrophils during CLP-induced sepsis by a mechanism dependent on Toll-like receptor/nuclear factor-κB pathway. Genetic or pharmacologic inhibition of CCR2 protected mice from CLP-induced mortality. This protection was associated with lower infiltration of neutrophils into the lungs, heart, and kidneys and reduced serum biochemical indicators of organ injury and dysfunction. Importantly, neutrophils from septic patients express high levels of CCR2, and the severity of patient illness correlated positively with increasing neutrophil chemotaxis to CCR2 ligands.Collectively, these data identify CCR2 as a key receptor that drives the inappropriate infiltration of neutrophils into remote organs during sepsis. Therefore, CCR2 blockade is a novel potential therapeutic target for treatment of sepsis-induced MODS.
Abstract 5593: A cancer-associated hyperphosphorylation site on topoisomerase I serine 506 as a biomarker for camptothecin sensitivity.
Authors: Keya Bandyopadhyay, Pingchuan Li, Ruth A. Gjerset
Journal: Cancer Research (2013)

Abstract Topoisomerase I (topo I) plays a central role in cancer as the target of a potent class of chemotherapeutic drugs derived from the plant alkaloid camptothecin that includes irinotecan and topotecan. We have identified a novel cancer-specific phosphorylation site at serine 506 in topo I (PS506), targeted by protein kinase CK2, that identifies cancer cells with elevated CK2, hyperphosphorylated topo I, increased topo I activity, and increased sensitivity to camptothecin. CK2 treatment of recombinant topo I in vitro also induces topo I hyperphosphorylation and expression of the PS506 epitope, and results in increased binding of topo I to supercoiled plasmid DNA. The hyperphosphorylated, PS506-form of topo I is more effective than the basal phosphorylated enzyme at relaxing plasmid supercoils but has a similar catalytic rate as the basal phosphorylated enzyme once bound to DNA. The PS506 epitope is not detected in normal cells or cancer cell lines with lower levels of CK2 activity. By experimentally manipulating CK2 activity in cancer cell lines, we have demonstrated a cause and effect relationship between CK2 activity, PS506 expression, camptothecin-induced cellular DNA damage, and cellular camptothecin sensitivity. The PS506 epitope is therefore an indicator of dysregulated, hyperphosphorylated topo I in cancer cells, and holds promise as a novel diagnostic biomarker that predicts tumor responsiveness to widely used topo I-targeted therapies. Citation Format: Keya Bandyopadhyay, Pingchuan Li, Ruth A. Gjerset. A cancer-associated hyperphosphorylation site on topoisomerase I serine 506 as a biomarker for camptothecin sensitivity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5593. doi:10.1158/1538-7445.AM2013-5593
Poisoning by Dry-cleaning Fluid
Authors: C. M. Illingworth
Journal: BMJ (1973)

severe pre-eclampsia may occur early enough to retard fetal growth.It is therefore im- portant to distinguish between pre-eclawpsia and eclampsia in such comparisons.The relatively small percentage of Yoruba primigravidae who are over 25 years of age tend to be overweight and to show a higher than average incidence of pre-eclampsia during pregnancy of the type seen in Europe.These women are usually in non- manual occupations.There is good evidence that hy,pertension is common in Yoruba women in middle life.-I am, etc.,
Evidence Linking Hypoglycemic Events to an Increased Risk of Acute Cardiovascular Events in Patients With Type 2 Diabetes
Authors: Stephen S. Johnston, Christopher Conner, Mark Aagren, David M. Smith, Jonathan Bouchard, Jason Brett
Journal: Diabetes Care (2011)

This retrospective study examined the association between ICD-9-CM-coded outpatient hypoglycemic events (HEs) and acute cardiovascular events (ACVEs), i.e., acute myocardial infarction, coronary artery bypass grafting, revascularization, percutaneous coronary intervention, and incident unstable angina, in patients with type 2 diabetes.Data were derived from healthcare claims for individuals with employer-sponsored primary or Medicare supplemental insurance. A baseline period (30 September 2006 to 30 September 2007) was used to identify eligible patients and collect information on their clinical and demographic characteristics. An evaluation period (1 October 2007 to 30 September 2008) was used to identify HEs and ACVEs. Patients aged ≥ 18 years with type 2 diabetes were selected for analysis by a modified Healthcare Effectiveness Data and Information Set algorithm. Data were analyzed with multiple logistic regression and backward stepwise selection (maximum P = 0.01) with adjustment for important confounding variables, including age, sex, geography, insurance type, comorbidity scores, cardiovascular risk factors, diabetes complications, total baseline medical expenditures, and prior ACVEs.Of the 860,845 patients in the analysis set, 27,065 (3.1%) had ICD-9-CM-coded HEs during the evaluation period. The main model retained 17 significant independent variables. Patients with HEs had 79% higher regression-adjusted odds (HE odds ratio [OR] 1.79; 95% CI 1.69-1.89) of ACVEs than patients without HEs; results in patients aged ≥65 years were similar to those for the entire population (HE OR 1.78, 95% CI 1.65-1.92).ICD-9-CM-coded HEs were independently associated with an increased risk of ACVEs. Further studies of the relationship between hypoglycemia and the risk of ACVEs are warranted.
Cloned Human Inward Rectifier K <sup>+</sup> Channel as a Target for Class III Methanesulfonanilides
Authors: J. Kiehn, B. Wible, E. Ficker, M. Taglialatela, A.M. Brown
Journal: Circulation Research (1995)

Abstract Methanesulfonanilide derivatives such as dofetilide are members of the widely used Class III group of cardiac antiarrhythmic drugs. A methanesulfonanilide-sensitive cardiac current has been identified as I Kr , the rapidly activating component of the repolarizing outward cardiac K + current, I K . I Kr may be encoded by the human ether-related gene (hERG), which belongs to the family of voltage-dependent K + (K v ) channels having six putative transmembrane segments. The hERG also expresses an inwardly rectifying, methanesulfonanilide-sensitive K + current. Here we show that hIRK, a member of the two-transmembrane-segment family of inward K + rectifiers that we have cloned from human heart, is a target for dofetilide. hIRK currents, expressed heterologously in Xenopus oocytes, are blocked by dofetilide at submicromolar concentrations (IC 50 =533 nmol/L at 40 mV and 20°C). The drug has no significant blocking effect on the human cardiac K v channels hK v 1.2, hK v 1.4, hK v 1.5, or hK v 2.1. The block is voltage dependent, use dependent, and shortens open times in a manner consistent with open-channel block. While steady state block is strongest at depolarized potentials, recovery from block is very slow even at hyperpolarized potentials (tau=1.17 seconds at −80 mV). Thus, block of hIRK may persist during diastole and might thereby affect cardiac excitability.
Multiplexed characterization of cancer immune response in FFPE biopsies - initial performance of a new approach
Authors: Chichung Wang, Rebecca King, Michael Feldman, Clifford Hoyt
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Recent successes with experimental PD-L1 and PD-1 drugs and with adoptive immunotherapy point to the tremendous potential clinical value of harnessing our immune systems to fight cancer. Assessing host interaction with malignant cells is most effectively achieved by phenotyping
Risk of bleeding complications with antiplatelet agents: Meta‐analysis of 338,191 patients enrolled in 50 randomized controlled trials
Authors: Victor L. Serebruany, Alex I. Malinin, Roswith M. Eisert, David C. Sane
Journal: American Journal of Hematology (2003)

Abstract Antiplatelet therapy has been the focus of extensive clinical investigations over the last two decades. A variety of agents and regimens have been advanced for the prevention and treatment of vascular disease. Despite the proven life‐saving clinical benefits of inhibiting platelets, this therapy is associated with an increased risk of bleeding. The objective of this study was to determine the risk of hemorrhage in the major classes of antiplatelet agents. Data from clinical trials published 1988–2002 in English were retrieved from MEDLINE, OVID, and CARDIOSOURCE. Only those studies in which patients had clinical follow‐up for at least 1 month and in which a full description of hemorrhagic complications was reported were included. Information on sample size, study design, duration, agent, patient characteristics, and bleeding severity was independently and blindly reviewed. Data from 51 clinical trials with a total of 338,191 patients were analyzed. The antiplatelet agents were divided into 6 groups: aspirin (ASA) &lt; 100 mg; ASA ≥ 100 mg; dipyridamole, thienopyridines; intravenous and oral GP IIb/IIIa inhibitors. The variance estimate and confidence intervals were calculated for each treatment assignment. Low‐dose aspirin and dipyridamole therapy were associated with the lowest risk of bleeding (3.6% and 6.7%, respectively). The highest rate of bleeding complications (44.6%) was associated with the GP IIa/IIIb inhibitors. Despite substantial differences in the reporting patterns of bleeding complications, low‐dose ASA and dipyridamole therapy were associated with the lowest risk. Surprisingly, doses of ASA ≥ 100 mg caused a relatively high hemorrhagic event rate, which was comparable to that of ADP‐receptor blockers. These findings should be considered when using combination antiplatelet and/or anticoagulant therapy with conventional doses of ASA. Am. J. Hematol. 75:40–47, 2004. © 2003 Wiley‐Liss, Inc.
Inhibition of Atherosclerosis by Cod-Liver Oil in a Hyperlipidemic Swine Model
Authors: Bonnie H. Weiner, Ira S. Ockene, Peter H. Levine, Henri F. Cuénoud, Marc Fisher, Brian F. Johnson, Assaad S. Daoud, John Jarmolych, David Hosmer, Mark H. Johnson, Anita Natale, Christine Vaudreuil, James J. Hoogasian
Journal: New England Journal of Medicine (1986)

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.
South Africans to get AIDS plan
Authors: Pat Sidley
Journal: BMJ (2007)

The South African government has finally introduced a full and far reaching plan to deal with its HIV/AIDS epidemic. But it will cost the country some 14bn rand (£970m; €1.4bn; $1.9bn) over the next five years. This amount was not planned for in the present budget for the year ahead.

The plan aims to give …
WHO to create international human resources database on health care
Authors: R. Dobson
Journal: BMJ (2003)

One in three countries in Africa and South East Asia has only one medical school for every 10 million people or more, a rate poorer than anywhere in Europe or the Americas, says a new report by researchers from the World Health Organization.

Nine out of 10 countries in the same two regions have fewer than 50 doctors per 100000 inhabitants, and about half of the countries have a similar density of nurses and midwives.

Such analyses and comparisons, however, may be subject to certain limitations, says the report. Classification of …
Identification and Structure of the Rhizobium galegae Common Nodulation Genes: Evidence for Horizontal Gene Transfer
Authors: Leena Suominen, Christophe Roos, Gilles Lortet, Lars Paulin, Kristina Lindström
Journal: Molecular Biology and Evolution (2001)

Rhizobia are soil bacteria able to fix atmospheric nitrogen in symbiosis with leguminous plants. In response to a signal cascade coded by genes of both symbiotic partners, a specific plant organ, the nodule, is formed. Rhizobial nodulation (nod) genes trigger nodule formation through the synthesis of Nod factors, a family of chitolipooligosaccharides that are specifically recognized by the host plant at the first stages of the nodulation process. Here, we present the organization and sequence of the common nod genes from Rhizobium galegae, a symbiotic member of the RHIZOBIACEAE: This species has an intriguing phylogenetic position, being symbiotic among pathogenic agrobacteria, which induce tumors instead of nodules in plant shoots or roots. This apparent incongruence raises special interest in the origin of the symbiotic apparatus of R. galegae. Our analysis of DNA sequence data indicated that the organization of the common nod gene region of R. galegae was similar to that of Sinorhizobium meliloti and Rhizobium leguminosarum, with nodIJ downstream of nodABC and the regulatory nodD gene closely linked to the common nod operon. Moreover, phylogenetic analyses of the nod gene sequences showed a close relationship especially between the common nodA sequences of R. galegae, S. meliloti, and R. leguminosarum biovars viciae and trifolii. This relationship in structure and sequence contrasts with the phylogeny based on 16S rRNA, which groups R. galegae close to agrobacteria and separate from most other rhizobia. The topology of the nodA tree was similar to that of the corresponding host plant tree. Taken together, these observations indicate that lateral nod gene transfer occurred from fast-growing rhizobia toward agrobacteria, after which the symbiotic apparatus evolved under host plant constraint.
The Beyond Within: The LSD Story
Authors: Donald E. Widmann
Journal: JAMA (1965)

The medical community was alarmed recently by the uncontrolled and somewhat-promiscuous use of "hallucinogens" in one of our major cities. The lay press contained many accounts suggesting the various hallucinogenic properties, but emphasized that the drugs seemed to provide the user with something of a mystic experience— what has been called "instant Zen." In<i>The Beyond Within</i>the author places these drugs in a historical perspective, discusses their effects on the mind, and suggests their potential as adjuncts in psychotherapy or as agents of chemical warfare. The book reflects a significant problem facing the researcher working with these drugs—the fact that it is difficult to convey the nature of the experience after taking such a drug. This reviewer has taken a hallucinogen as part of a research project, and can appreciate the difficulty the author had in choosing accounts from people under the influence of these drugs. The experience does
Teratogen may be implicated in lethal congenital syndrome
Authors: Elizabeth Rasche GonzÁlez
Journal: JAMA (1979)

An unidentified teratogen, as detrimental to fetal development as thalidomide, may lurk in our environment. That news comes from investigators who are now seeing infants born (in places as diverse as Alaska and Florida) with imperforate anus, renal agenesis or dysplasia, postaxial polydactyly, nail dysplasia, unusual facies, multiple frenula of the gums, laryngeal clefts, bifid or absent epiglottis, and additional anomalies that vary from case to case. The affected infant invariably dies shortly after birth. Autopsy reveals a bizarre hypothalamic tumor that has resulted in a malformed pituitary area. The resulting absence of functional pituitary tissue accounts for the hypopituitarism, hypoadrenalism, and, in males, microphallus that also characterize the syndrome. In four of six known cases, says Judith Hall, MD, the mothers reported exposure to herbicides or pesticides (including an unidentified substance sprayed on plants at a campsite and a common commercial fumigant for household use) early in the first
Gestational Diabetes Mellitus Causes Changes in the Concentrations of Adipocyte Fatty Acid–Binding Protein and Other Adipocytokines in Cord Blood
Authors: Henar Ortega-Senovilla, Ute Schaefer-Graf, Katrin Meitzner, Michael Abou-Dakn, Kristof Graf, Ulrich Kintscher, Emilio Herrera
Journal: Diabetes Care (2011)

OBJECTIVE To determine the concentrations of adipocyte fatty acid–binding protein (AFABP) and other adipocytokines in maternal and cord serum of pregnant women with gestational diabetes mellitus (GDM) and of control subjects and to relate them to indexes of insulin sensitivity. RESEARCH DESIGN AND METHODS In 86 control and 98 GDM pregnant women, venous blood was collected before vaginal delivery and arterial blood from cord immediately after delivery. Serum insulin and adipocytokines were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS GDM women had higher prepregnancy BMI, and data were adjusted for it. Maternal serum insulin, insulin-to-glucose ratio, homeostasis model assessment (HOMA), AFABP, and retinol-binding protein 4 (RBP4) were higher and adiponectin was lower in GDM than in control subjects, whereas serum glucose, insulin, insulin-to-glucose ratio, HOMA, nonesterified fatty acids, and RBP4 were higher and glycerol, AFABP, and adiponectin were lower in cord blood serum of GDM than of control subjects. AFABP and adiponectin in cord serum of control subjects were higher than in maternal serum; in GDM women no difference was found for AFABP in cord versus maternal serum, although adiponectin remained higher in cord. Values of leptin in both groups were lower in cord than in maternal serum, and those of RBP4 were lower in only GDM women. CONCLUSIONS It is suggested that fetal tissues are the main source of cord arterial serum AFABP, and in GDM fetuses AFABP values correlate with adiposity markers. A downregulation of adiponectin and upregulation of RBP4 in GDM mothers and their fetuses may be related to their insulin-resistant condition, whereas changes in AFABP do not seem to be related.
Natural history of donor-transmitted atherosclerosis in transplant patients: serial intravascular ultrasound study
Authors: S.R. Kapadia, T.D. Crowe, K.M. Ziada, J.B. Young, R.E. Hobbs, V. Guetta, W.A. Magyar, S.E. Nissen, E.M. Tuzcu
Journal: Journal of the American College of Cardiology (1998)