tbuckley/cabot-search huggingface dataset:
Gene Expression Profiles Associated with the Presence of a Fibrotic Focus and the Growth Pattern in Lymph Node–Negative Breast Cancer
Authors: Gert G. Van den Eynden, Marcel Smid, Steven J. Van Laere, Cecile G. Colpaert, Ilse Van der Auwera, Trinh Xuan Bich, Peter van Dam, Michael A. den Bakker, Luc Y. Dirix, Eric A. Van Marck, Peter B. Vermeulen, John A. Foekens
Journal: Clinical Cancer Research (2008)

Abstract Purpose: A fibrotic focus, the scar-like area found in the center of an invasive breast tumor, is a prognostic parameter associated with an expansive growth pattern, hypoxia, and (lymph)angiogenesis. Little is known about the molecular pathways involved. Experimental Design: Sixty-five patients were selected of whom microarray data of the tumor and H&amp;E slides for histologic analysis were available. The growth pattern and the presence and size of a fibrotic focus were assessed. Differences in biological pathways were identified with global testing. The correlations of growth pattern and fibrotic focus with common breast cancer signatures and with clinicopathologic variables and survival were investigated. Results: Tumors with a large fibrotic focus showed activation of Ras signaling and of the hypoxia-inducible factor-1α pathway. Furthermore, unsupervised hierarchical cluster analysis with hypoxia- and (lymph)angiogenesis-related genes showed that hypoxia-inducible factor-1α, vascular endothelial growth factor A, and carbonic anhydrase 9 were overexpressed. The presence of a fibrotic focus, especially a large fibrotic focus, was associated with the basal-like subtype (P = 0.009), an activated wound-healing signature (P = 0.06), and a poor-prognosis 76-gene signature (P = 0.004). The presence of a fibrotic focus (P = 0.02) and especially of a large fibrotic focus (P = 0.004) was also associated with early development of distant metastasis. Conclusions: Our results sustain the hypothesis that hypoxia-driven angiogenesis is essential in the biology of a fibrotic focus. Ras and Akt might play a role as downstream modulators. Our data furthermore suggest that vascular endothelial growth factor A does not only drive angiogenesis but also lymphangiogenesis in tumors with a fibrotic focus. Our data also show an association between the presence of a fibrotic focus and infaust molecular signatures.
Fifteen-Year Follow-up of Association Between Telomere Length and Incident Cancer and Cancer Mortality
Authors: Peter Willeit, Johann Willeit, Anita Kloss-Brandstätter, Florian Kronenberg, Stefan Kiechl
Journal: JAMA (2011)

To the Editor: Telomeres are nucleoprotein structures that cap the ends of chromosomes and confer chromosomal stability. Telomere shortening to a critical length due to extensive DNA replication or oxidative stress facilitates genomic mutations and may induce malignant transformation.1
Circulatory Changes in Acute Glomerulonephritis
Authors: VALENTINO DEFAZIO, RAYMOND C. CHRISTENSEN, TIMOTHY J. REGAN, LESEM J. BAER, YOSHIKAZU MORITA, HARPER K. HELLEMS
Journal: Circulation (1959)

Conflicting opinions have been expressed as to the mechanism of pulmonary and peripheral congestion frequently observed in the oliguric stage of acute glomerulonephritis. Hemodynamic studies in 7 patients studied during the oliguric edematous phase of the disease demonstrated that these patients have high ventricular filling pressures associated with an increase in cardiac output and are, therefore, examples of a high output congestive state.
ABCC Drug Efflux Pumps and Organic Anion Uptake Transporters in Human Gliomas and the Blood-Tumor Barrier
Authors: Holger Bronger, Jörg König, Kathrin Kopplow, Hans-Herbert Steiner, Rezvan Ahmadi, Christel Herold-Mende, Dietrich Keppler, Anne T. Nies
Journal: Cancer Research (2005)

Delivery of therapeutic agents to the brain and its neoplasms depends on the presence of membrane transport proteins in the blood-brain barrier and in the target cells. The cellular and subcellular localization of these membrane transporters determines the drug accessibility to the brain and its tumors. We therefore analyzed the expression and localization of six members of the multidrug resistance protein family of ATP-dependent efflux pumps (ABCC1-ABCC6, formerly MRP1-MRP6) and of six organic anion uptake transporters (OATP1A2, OATP1B1, OATP1B3, OATP1C1, OATP2B1, and OATP4A1) in 61 human glioma specimens of different histologic subtypes. Real-time PCRs indicated expressions of ABCC1, ABCC3, ABCC4, and ABCC5. In addition, we detected expressions of the OATP uptake transporter genes SLCO1A2, SLCO1C1, SLCO2B1, and SLCO4A1. At the protein level, however, only OATP1A2 and OATP2B1 were detectable by immunofluorescence microscopy in the luminal membrane of endothelial cells forming the blood-brain barrier and the blood-tumor barrier, but not in the glioma cells. ABCC4 and ABCC5 proteins were the major ABCC subfamily members in gliomas, localized both at the luminal side of the endothelial cells and in the glioma cells of astrocytic tumors and in the astrocytic portions of oligoastrocytomas. These results indicate that expression of ABCC4 and ABCC5 is associated with an astrocytic phenotype, in accordance with their expression in astrocytes and with the higher chemoresistance of astrocytic tumors as compared with oligodendrogliomas. Our data provide a basis for the assessment of the role of uptake transporters and efflux pumps in the accessibility of human gliomas for chemotherapeutic agents.
Purpura Due to Trichlormethiazide
Authors: Lawrence R. Loftus
Journal: JAMA (1962)

MANY DRUGS have been reported to cause purpura, both thrombocytopenic and nonthrombocytopenic. The most recent of these drugs have been quinidine, sulfamethoxypyridazine, sodium (Sodium Para-) aminosalicylate, chloroquine, and meprobamate. Jaffe and Kierland reported the first 2 cases of purpura due to chlorothiazide in 1958. Both of their cases were nonthrombocytopenic. In 1960 6 cases of thrombocytopenic purpura due to chlorothiazide and hydrochlorothiazide were reported to the study group on blood dyscrasias of the AMA Council on Drugs. We recently were able to study a case of nonthrombocytopenic purpura due to a closely related diuretic, trichlormethiazide (Naqua). This is the first reported case of purpura due to this drug.  Report of a Case  A 51-year-old female was first seen by one of us in December, 1960, for an internist's evaluation of chest pain. The patient had previously been treated at the clinic for duodenitis. There was no past history of edema
THE RELATION OF EYE-STRAIN TO CHRONIC HEADACHES.
Authors: S. W. S. TOMS
Journal: JAMA (1907)

There is no one symptom so frequently complained of to the general practitioner as that of headache. It is the burden of suffering of civilized peoples. It is heard in connection with almost every case of impaired health, functional or organic. The etiology of it we, as physicians, should most persistently endeavor to determine in each case. The late Dr. E. C. Seguin said: "The thorough study of a case of headache is one of the most difficult problems of medicine," and Alfred L. Loomis designated it as a "symptom of exceedingly difficult interpretation." The reflex headaches or neuralgias due to essential eye-strain comprise the greater percentage of all cases met with. I have the records of over 1,280 eye examinations that justifies me in stating 90 per cent. of all those complaining of this distressing malady had ocular defects. These examinations—most of which were made as part of routine
Abstract 1652: Global proteomics analysis by SILAC (stable isotope labelling with amino acid in cell culture) in hepatocellular carcinoma treated by sorafenib: identification of phospho-AKT activation as a resistant mechanism
Authors: Wen-Chi Feng, Chih-Hung Hsu, Shiou-Der Lin, Ming Gao, Pei-Yen Yeh, Lu-Ping Chow, Ann-Lii Cheng
Journal: Cancer Research (2010)

Abstract Sorafenib, a multikinase inhibitor against Raf kinase and vascular endothelial growth factor receptor (VEGFR), was recently approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the majority of HCC are inherently resistant to sorafenib. A global proteomic approach was applied to delineate the molecular mechanisms affecting the effectiveness of sorafenib in HCC cells. HCC cells (Huh7, SKHep1, and PLC5) were treated with sorafenib and analyzed by the SILAC (Stable Isotope Labeling with Amino acids in Cell culture) methodology. A total of 354 phosphoproteins were identified from untreated Huh7 cells (labeled with light amino acid, designated as L) and sorafenib-treated cells (labeled with heavy amino acid, designated as H). Forty-five proteins with high L/H ratio, indicating decreased expression after sorafenib treatment, were recognized. Among them, downstream proteins of Raf kinase, which are expected to be downregulated by sorafenib, were found. On the other hand, 30 proteins with low L/H ratio, indicating increased expression after sorafenib treatment, were recognized. Biological interaction network analysis of the phosphoproteome using IPA (ingenuity pathway analysis) method revealed that several signaling pathways including PI3K/AKT were significantly altered in sorafenib-treated Huh7 cells. To validate the relevance of these pathway alterations, the expression of p-AKT (Ser 473) was examined and was found significantly upregulated by sorafenib. Downregulation of AKT by siRNA attenuated the upregulation of p-AKT induced by sorafenib and enhanced the cytotoxicity of sorafenib in Huh7 cells. Combination of MK-2206, an allosteric inhibitor of AKT, abolished sorafenib-induced p-AKT upregulation, and resulted in a synergistic anti-proliferative effect in HCC cells. In conclusion, an unbiased and global phosphoproteomic approach by SILAC proves useful in identifying molecules altered by sorafenib in HCC cells; and by using this approach we showed that targeting AKT is a potentially useful strategy to improve the efficacy of sorafenib in advanced HCC. (The study was supported by the grant NSC 97-2628-B-002-004-MY3 from National Science Council of Taiwan and a research grant from Merck &amp; Co., Inc.) 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 1652.
Influenza and Other Virus Infections of the Respiratory Tract
Authors: F. Robert Fekety
Journal: JAMA (1965)

This second edition of Professor Stuart-Harris' short monograph on viral respiratory infections will be useful to those who seek a brief survey of this important, fascinating, complex, and rapidly expanding field, but most of its information is covered well in other recent texts and reviews. Approximately one half of the book is devoted to influenza, its diagnosis, epidemiology, pathology, clinical aspects, and prevention. Clinicians reading these sections are likely to come away with the impression that we haven't learned much about this disease in the past ten years; this is probably not fair to many investigators, including the author of this monograph. The remainder of the volume is devoted to the picornaviruses, adenoviruses, para-influenza, respiratory syncytial viruses, and the agents of primary atypical pneumonia. Confusion in this area is the rule because clinical syndromes overlap, partly because they are strikingly modified by age and prior immunity. Agents causing severe lower-respiratory-tract
Each Degree of Glucose Intolerance in Pregnancy Predicts Distinct Trajectories of β-Cell Function, Insulin Sensitivity, and Glycemia in the First 3 Years Postpartum
Authors: Caroline K. Kramer, Balakumar Swaminathan, Anthony J. Hanley, Philip W. Connelly, Mathew Sermer, Bernard Zinman, Ravi Retnakaran
Journal: Diabetes Care (2014)

Glucose intolerance in pregnancy predicts an increased risk of future type 2 diabetes mellitus (T2DM) that is proportional to the severity of antepartum dysglycemia (i.e., highest in women with gestational diabetes mellitus [GDM], followed by those with milder dysglycemia). However, the pathophysiologic changes driving this risk are not known. Thus, we evaluated the longitudinal changes in β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum after gestational dysglycemia.A total of 337 women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT at 3 months, 1 year, and 3 years postpartum. The antepartum GCT/OGTT identified four gestational glucose tolerance groups: GDM (n = 105); gestational impaired glucose tolerance (GIGT; n = 60); abnormal GCT, followed by normal glucose tolerance (NGT) on the OGTT (abnormal GCT NGT; n = 96); and normal GCT with NGT (n = 76).At each of 3 months, 1 year, and 3 years postpartum, the prevalence of glucose intolerance increased from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all P < 0.001), whereas β-cell function, assessed by the Insulin Secretion-Sensitivity Index-2 (ISSI-2), and insulin sensitivity (Matsuda index), progressively decreased across the groups (all P < 0.002). Each group predicted distinct trajectories of ISSI-2, Matsuda index, and fasting and 2-h glucose (all P < 0.001). Notably, GDM, GIGT, and abnormal GCT NGT predicted varying rates of declining β-cell function and insulin sensitivity, as well as rising glycemia, compared with normal GCT NGT.Each degree of gestational glucose intolerance predicts distinct trajectories of β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum that drive their differential risk of future T2DM.
Breast Feeding Contraindications
Authors: Thomas E. Frothingham
Journal: JAMA (1974)

To the Editor.—  Those of us who devote significant effort to getting human milk into babies, where it belongs, must view Dr. Vorherr's extraordinary list (227:676, 1974) of contraindications to breast feeding with dismay. Most physicians would find his list excessive. Family history of breast cancer, for example, should not be a contraindication to nursing; today's knowledge of the factors that contrive to produce breast cancer is not adequate to support such a sweeping (and illogical for male babies) recommendation. There is even less justification for advising against breast feeding because of heavy smoking, mastitis, postpartum hemorrhage, poor nutrition, epilepsy, and neuroses. With regard to Dr. Voherr's list of drugs, the type, dose, and duration must be considered, as each case is judged individually.  Nursing is important; it is contraindicated rarely, and only when common sense and scientific fact blended by careful reason clearly so indicate.
Locus for the inducible, but not a constitutive, nitric oxide synthase cosegregates with blood pressure in the Dahl salt-sensitive rat.
Authors: A Y Deng, J P Rapp
Journal: Journal of Clinical Investigation (1995)

Alleles of the inducible nitric oxide synthase locus (Nos2) cosegregated highly significantly (P < 0.0001) with blood pressure in an F2 population [F2(S x MNS), n = 171] derived from a cross of inbred Dahl salt-sensitive (S) rats with Milan normotensive rats (MNS). In contrast, alleles at the constitutive brain nitric oxide synthase locus (Nos1) did not cosegregate with blood pressure in several F2 populations. Nos2 was mapped on rat chromosome 10. Nine genetic markers, including the angiotensin-converting enzyme (Ace) and Nos2 loci spanning roughly 46 cM on rat chromosome 10, all cosegregated strongly with blood pressure in the F2(S x MNS) population. Nos2 showed the highest LOD score of 6.3. Ace and Nos2 are 30 cM apart. In an F2 population [F2(S x WKY), n = 159] derived from a cross of S rats with Wistar-Kyoto (WKY) rats, Nos2 alleles did (P = 0.0070), but Ace alleles did not (P = 0.91), cosegregate with blood pressure. We conclude that the Nos2 locus rather than the Nos1 locus is a candidate for influencing blood pressure in the S rat. There are probably two separate but linked quantitative trait loci (QTL) for blood pressure on rat chromosome 10, one marked by Ace and the other marked by Nos2. In F2(S x MNS) functionally variant alleles at both QTL influence blood pressure, but in F2(S x WKY) only the QTL marked by Nos2 is segregating alleles influencing blood pressure.
The tricuspid valve annulus: study of size and motion in normal subjects and in patients with tricuspid regurgitation.
Authors: C Tei, J P Pilgrim, P M Shah, J A Ormiston, M Wong
Journal: Circulation (1982)

The tricuspid valve leaflets and their annular attachments were recorded by two-dimensional echocardiography from a view of the right ventricular inflow tract obtained by placing the transducer at an intermediate position between the left ventricular apex and the left lower sternal border. The transducer was rotated, and recordings were made at 30 degrees rotational intervals around the circumference of the tricuspid valve annulus. The cyclical pattern of variations in tricuspid annular size was studied with 12 measurements made during the cardiac cycle in five normal subjects. Annular areas and circumferences were measured. The overall motion pattern was similar to that reported in normal mitral valve annular study. Subsequently, in 16 normal subjects and 18 patients with tricuspid regurgitation, the maximum and minimum tricuspid annular sizes and their percent reduction were measured. The mean maximum annular circumference and area were 11.9 +/- 0.9 cm (mean +/- SD) and 11.3 +/- 1.8 cm2 in normal subjects. They were significantly greater in tricuspid regurgitation (14.0 +/- 0.7 cm and 15.8 +/- 1.8 cm2, respectively). The mean minimum annular sizes were much larger in tricuspid regurgitation (12.5 +/- 0.6 cm and 13.0 +/- 1.4 cm2) than in normal subjects (9.6 +/- 0.9 cm, 7.6 +/- 1.4 cm2). Thus, the percent reduction of annular circumference and area were significantly decreased in tricuspid regurgitation. For anatomic correlations, measurements of the tricuspid annular circumference were made at autopsy in 18 hearts without underlying valvular disease. The annular circumference was measured in the fresh and fixed states. The measurement in the fresh state was 13.5 +/- 0.8 cm and in the fixed state was 12.0 +/- 0.8 cm. The values measured in the fixed hearts were more similar to measurements obtained by echocardiography in a group of normal subjects. Thus, tricuspid annular reconstruction by the new two-dimensional echocardiographic method provides additional information about normal and abnormal size and function of the tricuspid valve annulus.
Familial Insulin Resistance with Acanthosis Nigricans, Acral Hypertrophy, and Muscle Cramps
Authors: Jeffrey S. Flier, James B. Young, Lewis Landsberg
Journal: New England Journal of Medicine (1980)

RESISTANCE of the target cell to insulin action coexists with the skin lesion acanthosis nigricans in several distinct clinical syndromes.1 The Type A syndrome of insulin resistance, in which insulin resistance and acanthosis nigricans occur together with polycystic ovaries in young females, is one example.1 , 2 Receptors for insulin were reduced in concentration on circulating monocytes in three of the first four patients studied.2 , 3 Because insulin resistance can be clinically silent and acanthosis nigricans is often not observed, the incidence of this syndrome is unknown. Fundamental aspects of the disorder that remain unexplored include the cause of the receptor (or postreceptor) . . .
Fetal HLA typing in β thalassaemia: implications for haemopoietic stem-cell transplantation
Authors: Maria Grazia Orofino, Francesca Argiolu, Maria Adele Sanna, Maria Cristina Rosatelli, Teresa Tuveri, Maria Teresa Scalas, Manuela Badiali, Paola Cossu, Rosalba Puddu, Maria Eliana Lai, Antonio Cao
Journal: The Lancet (2003)
HEALTH PROBLEMS IN WAR HOUSING
Authors: DONALD K. FREEDMAN
Journal: JAMA (1942)

There is little precedent in this country for action with regard to the health problems arising in connection with wartime public housing. The United States entered the first world conflict late in the course of the war. War industries generally made use of existing plants, enlarging them or stepping up production. Local communities were generally able to house the new workers fairly readily. In this war, production is on a greater scale. We are supplying other nations with huge amounts of equipment. We have had little time for preparation. As a result of the rapidity with which production has had to be organized, severe dislocations in population have occurred. Almost overnight communities have arisen in the midst of barren regions, and towns have become cities without warning. <h3>PUBLIC HOUSING</h3> These rapid changes have created extraordinary housing problems. As a result of the unbearable and dangerous living conditions in some regions,
Chlorination of Water Supplies to Control Legionella May Corrode the Pipes
Authors: Philip B. Mead
Journal: JAMA (1988)

<h3>To the Editor.—</h3> We read with interest the article by Helms et al<sup>1</sup>that describes continuous hyperchlorination of a hospital water system and wish to comment on their observations in view of our own experience with this technique. Following two major outbreaks of legionnaires' disease at this institution in 1980, continuous hyperchlorination of the hospital's hot water system was begun in 1981, with attempts made to maintain chlorine levels of 1.5 mg/L of free chlorine. Although<i>Legionella</i>could no longer be cultured from hot water samples, by 1984 major corrosion damage to the copper plumbing system had occurred, resulting in unacceptable maintenance costs, disruption of patient care activities, and concern about disintegration of the entire water distribution system. An environmental engineer (J.W.P.) was consulted and documented two different types of copper corrosion: (1) a slow, uniform corrosion that occurred when chlorine levels were low and the water pH somewhat acidic
Mitral-Valve Prolapse: A Clinical Spectrum
Authors: Michael Lesch
Journal: New England Journal of Medicine (1976)

Definition of an association between non-ejection clicks and late systolic murmurs, and the observation that patients with these physical findings usually do not manifest clinically important cardiac dysfunction are attributable to Gallavardin in the first third of the century.1 , 2 The auscultatory phenomena of non-ejection clicks and late systolic murmurs were originally thought to be due to extracardiac events and generated little interest in the cardiologic literature until abnormalities of the mitral apparatus were suggested by Barlow3 and Reid4 in the early 1960's as the source of abnormal cardiac sounds. Criley et al.,5 in 1966, then demonstrated with angiographic technic that . . .
A versatile denaturing HPLC approach for human β‐globin gene mutation screening
Authors: Stavros N. Bournazos, Aggeliki Tserga, George P. Patrinos, Manoussos N. Papadakis
Journal: American Journal of Hematology (2006)

Abstract Hemoglobinopathies represent the most common genetic disorder worldwide, with a higher prevalence among populations with a history of malaria endemicity. More than 690 mutations in the human β‐globin gene are usually the cause of β‐type hemoglobinopathies. Here, we report a rapid and highly sensitive β‐globin gene mutation screening approach based on denaturing high‐performance liquid chromatography (DHPLC), which contrary to the previously described ones can be used in every HPLC apparatus. The sensitivity and specificity of the method were tested in 120 healthy Greek subjects and 25 β‐thalassemia heterozygotes and homozygotes, in which 11 different β‐globin sequence variations had been previously characterized by denaturing gradient gel electrophoresis. Using this method, we were able to rapidly identify the commonest β‐globin gene mutations, accounting for more than 90% of the mutant β‐globin alleles reported for the Hellenic population. Compared to classical mutation screening approaches, our DHPLC approach provides the means for rapid, highly sensitive, cost‐effective, and semi‐automated simultaneous mutational scanning of a large number of samples. Am. J. Hematol., 2006, © 2006 Wiley‐Liss, Inc.