tbuckley/cabot-search huggingface dataset:
The effect of vasopressin on phosphate transport in the proximal tubule of the dog.
Authors: S F Wen
Journal: Journal of Clinical Investigation (1974)

Recollection micropuncture study was performed in 11 thyroparathyroidectomized dogs during antidiuresis to determine the effect of continuous vasopressin infusion at 50 mU/kg/h on proximal tubule phosphate and sodium transport. The animals were divided into two groups according to changes in mean arterial blood pressure. In the first group (five dogs) with increased blood pressure and glomerular filtration rate (GFR), mean proximal tubule fluid-to-plasma inulin ratio fell significantly from 1.69 to 1.53, whereas it remained unchanged at 1.60 in the second group (six dogs) with no change in blood pressure. In contrast, mean proximal tubule fluid-to-plasma ultrafilterable phosphate ratio increased consistently in both groups, regardless of blood pressure changes. Since natriuresis as well as phosphaturia were observed in all animals, the sodium effect of vasopressin in the distal nephron must be mainly responsible for the natriuresis. It was concluded that vasopressin, when given in the doses employed, inhibits phosphate transport in the proximal tubule and sodium reabsorption in the distal nephron. An additional effect on proximal tubule sodium reabsorption appears to be related to the rise in blood pressure and GFR secondary to vasopressin administration.
Abstract 5318: DPC4 loss results in the activation of alternative oncogenic pathways in pancreatic cancer
Authors: Jacqueline A. Brosnan, Catherine M. White, Christine A. Iacobuzio-Donahue
Journal: Cancer Research (2012)

Abstract Introduction: Pancreatic cancer remains one of the most lethal forms of cancer, with a five-year survival rate of less than five percent. Many of these patients succumb to complications from metastasis. We have shown that genetic inactivation of DPC4, a major factor in TGF-β signaling, is significantly correlated with widespread metastasis in pancreatic cancer patients at autopsy. We hypothesize that DPC4 loss may be driving pancreatic cancer metastasis by forcing the TGF-β signal down an alternative pathway. Methods: DPC4 was stably restored into three cell lines that harbor a homozygous deletion of the locus (A2.1, A6L, and BxPC3), forming isogenic pairs of DPC4−/− and DPC4+ cells. Matched DPC4−/− and DPC4+ cells were treated with TGF-β1 for 24 hours prior to protein extraction. Immunoblotting was performed for total and phospho Akt (Pi3K pathway), p44-42 (ERK pathway), and Stat3 (JAK-Stat pathway), as well as nuclear and cytoplasmic p65 (NFκB pathway), as these networks have previously been identified as being activated by TGF-β. Immunohistochemistry was performed on 50 surgically resected pancreatic cancers for pAkt. Results: DPC4 was successfully introduced into DPC4−/− cells, as evidenced by semi-quantitative PCR for DPC4, as well as a TGF-β luciferase assay. DPC4+ cells displayed characteristic differences in cell behavior, such as decreased proliferation, migration, and invasion, compared to DPC4−/− cells. Western blot analysis of Smad-independent TGF-β pathways in three sets of DPC4-complemented pancreatic cancer cell lines revealed patterns of preferential activation of the Pi3K and ERK signaling pathways in cells lacking DPC4. In surgically-resected pancreatic cancers, activation of Pi3K was associated with the presence of lymph node metastases (p=0.03), while concomitant DPC4 loss and Pi3K pathway activity was associated with poor survival in pancreatic cancer patients (p=0.02). Conclusions: Restoration of DPC4 into DPC4−/− cells results in the abrogation of Pi3K and ERK signaling, and simultaneous DPC4 loss and Pi3K activation correlates to a poor prognosis of pancreatic cancer patients at surgery. Further studies will confirm whether genotype-specific activation of the ERK and Pi3K pathways plays a role in pancreatic cancer cell behavior, particularly those processes that directly impact metastasis (i.e. migration and invasion). Nevertheless, it is intriguing to consider the Pi3K and ERK pathways as therapeutic targets in pancreatic cancer patients with loss of DPC4. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5318. doi:1538-7445.AM2012-5318
Message From China
Authors: Robert H. Moser
Journal: JAMA (1974)

In this issue ofThe Journal(p 1527), Tavassoli, a young hematologist from the University of Tehran, presently at Scripps Clinic and Research Foundation in La Jolla, stresses the curious failure of the governments of many "developing countries" to come to grips with the grim medical realities existing right within their own borders. He finds this deficiency to be especially prominent in the area of medical education. Efforts to emulate Western medicine have resulted, not unpredictably, in "specialty orientation," which, he notes, is totally inappropriate to the needs of the mother country. Further, the young physicians themselves, who are "overtrained," without incentive or facilities to utilize their newly acquired talents, and without the skills or disposition to tackle the enormous practical problems at home, become disillusioned and discontented, and eventually defect to whence they were trained—the West. Yet, in many dark regions of the world, survival, not
Review: Evidence is insufficient to evaluate effectiveness of antiviral therapies for chronic hepatitis B
Authors: J. Reichen
Journal: Annals of Internal Medicine (2009)

Source Citation Shamliyan TA, Macdonald R, Shaukat A, et al. Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference. Ann Intern Med. 2009;150:111-24. 19124812
A Short History of the Gout and the Rheumatic Diseases
Authors: John H. Talbott
Journal: JAMA (1964)

In January, 1962, W. S. C. Copeman of London delivered a series of lectures at the University of California at Los Angeles on the history of rheumatic diseases. The lectures were expanded and recently have been published. The maladies discussed included gout, acute rheumatism (rheumatic fever), chorea, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, and nonarticular rheumatism. The author, a distinguished rheumatologist and skilled clinician, editor of the<i>Annals of Rheumatic Diseases</i>, senior physician for rheumatic diseases at Middlesex Hospital of London, and chairman of the faculty of the History of Medicine of the Worshipful Society of Apothecaries, London, has shown himself thoroughly equal to the task. The volume is well written and appropriately illustrated. Not since 1900, when Armand Delpeuch published his history,<i>La Goutte et le Rhumatisme</i>, has such an authoritative and worthwhile text appeared.
Medicalising unhappiness: new classification of depression risks more patients being put on drug treatment from which they will not benefit
Authors: C. Dowrick, A. Frances
Journal: BMJ (2013)

The coinhibitory receptor programmed death-1 (PD-1) maintains immune homeostasis by negatively regulating T cell function and survival. Blockade of PD-1 increases the severity of graft-versus-host disease (GVHD), but the interplay between PD-1 inhibition and T cell metabolism is not well studied. We found that both murine and human alloreactive T cells concomitantly upregulated PD-1 expression and increased levels of reactive oxygen species (ROS) following allogeneic bone marrow transplantation. This PD-1<sup>Hi</sup>ROS<sup>Hi</sup> phenotype was specific to alloreactive T cells and was not observed in syngeneic T cells during homeostatic proliferation. Blockade of PD-1 signaling decreased both mitochondrial H<sub>2</sub>O<sub>2</sub> and total cellular ROS levels, and PD-1–driven increases in ROS were dependent upon the oxidation of fatty acids, because treatment with etomoxir nullified changes in ROS levels following PD-1 blockade. Downstream of PD-1, elevated ROS levels impaired T cell survival in a process reversed by antioxidants. Furthermore, PD-1–driven changes in ROS were fundamental to establishing a cell's susceptibility to subsequent metabolic inhibition, because blockade of PD-1 decreased the efficacy of later F<sub>1</sub>F<sub>0</sub>-ATP synthase modulation. These data indicate that PD-1 facilitates apoptosis in alloreactive T cells by increasing ROS in a process dependent upon the oxidation of fat. In addition, blockade of PD-1 undermines the potential for subsequent metabolic inhibition, an important consideration given the increasing use of anti–PD-1 therapies in the clinic.
Variation in the level of fetal hemoglobin in (δβ)°‐thalassemia heterozygotes with different numbers of α‐globin genes
Authors: C. Öner, A. Gurgey, C. Altay, F. Kutlar, T. H. J. Huisman
Journal: American Journal of Hematology (1990)

Abstract The Sicilian type of (αβ)°‐thalassemia characterized by a ˜13 kb deletion, was present in a Turkish boy who is a homozygote and in his heterozygous parents who are first cousins. The father with ˜21% Hb F had five α‐globin genes (αα/ααα) and the mother with ˜10% Hb F had an α‐thal‐2 heterozygosity (αα/‐α). The difference in Hb F level is explained by a decreased formation of α 2 γ 2 tetramers in the mother with an α‐chain deficiency while the extra α‐globin gene in the father will promote Hb F production.
DUAL DIAGNOSIS OF PRENATAL HÆMOPHILIA A BY MEASUREMENT OF FETAL FACTOR VIIIC AND VIIIC ANTIGEN (VIIICAg)
Authors: R.S Mibashan, C.H Rodeck, R.A Furlong, L Bains, I.R Peake, J.K Thumpston, R Gorer, A.L Bloom
Journal: The Lancet (1980)
Non-invasive assessment of ventricular damage in rats with myocardial infarction
Authors: R. G Baily, J. C Lehman, S. S Gubin, T. I Musch
Journal: Cardiovascular Research (1993)

Objective: The aim was to evaluate whether two dimensional echocardiographic/Doppler (echo/Doppler) techniques could be used to detect left ventricular damage rapidly, accurately, and non-invasively in rats with a myocardial infarction. Methods: Female Wistar rats were initially subjected to either a sham operation or surgery to induce a myocardial infarct by ligating the left main coronary artery. Following a minimum of six weeks to recover from the surgery, all rats were reanaesthetised and cardiac and stroke indexes were determined at similar heart rates, using echo/Doppler techniques. Postmortem histological assessment of myocardial infarct size was compared with the non-invasive detection of left ventricular wall motion abnormalities, left ventricular dilatation, and the presence of a left ventricular aneurysm found in the living animal. Results: Rats with myocardial infarction (n=8) showed a 33(SEM 4)% reduction (p < 0.01) in cardiac index (due to a 33% reduction in stroke index) when compared to their non-infarcted counterparts (n=5). In addition, a significant correlation (r=0.84; n=25; p < 0.01) was found between the assessment of left ventricular damage via non-invasive echo/ Doppler measurements and the histological determination of infarct size. Conclusions: These results support the conclusion that two dimensional echo/Doppler techniques can be used to estimate rapidly and non-invasively the degree of left ventricular damage produced in living rats with myocardial infarction when compared to non-infarcted controls. Cardiovascular Research 1993;27:851-855
I remember it well
Authors: S. Vaisrub
Journal: JAMA (1969)

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Pathogenesis of inflammatory bowel disease: transcription factors in the spotlight
Authors: M F NEURATH
Journal: Gut (1998)

See article on page 477 

Dysregulated cytokine production by mucosal lymphocytes and macrophages has been implicated in the pathogenesis of both Crohn’s disease and ulcerative colitis, the two major forms of human inflammatory bowel disease (IBD).1 Over the past few years, various murine models of chronic intestinal inflammation resembling IBD have been discovered which have provided important clues as to the nature of this dysregulation and to its possible treatment with cytokines.2 Thus, in studies of several of the models most closely resembling Crohn’s disease it has been shown that production of large amounts of Th1-type cytokines—for example, interferon γ, by T cells is a major and essential feature of the inflammation.2 In addition, it has been shown that this disease causing Th1 cytokine response can be counteracted by induction of a suppressor response involving the generation of T cells producing Th2-type cytokines or transforming growth factor …
Presidential Address on Physiology and the Healing Art: Delivered at the Opening of the Winter Session of the Ulster Medical Society, November 1st, 1900
Authors: W. H. Thompson
Journal: BMJ (1900)

PHYSIOLOGY was formerly said to be the basis of rational medicine.It is a saying which has grown somewhat worn and old, but I fear the amount of conviction which it carries to the breast of the average medical man has not increased with its age.These are sentiments which perhaps I ought not to reecho, but no real harm is ever done by fairly looking at facts in the face.All the less likely is this to happen in the present instance, because I believe the saying is in reality more true to-day than when it was first uttered.The intiriate connection has only been obscured by other developments; the dissociation is more apparent than real.
Carcinogenicity of by-products of disinfection in mouse and rat liver.
Authors: S L Herren-Freund, M A Pereira
Journal: Environmental Health Perspectives (1986)

By-products of disinfection were tested for initiating and/or promoting activity in rat liver by using the rat liver foci bioassay. The assay uses an increased incidence of gamma-glutamyltranspeptidase-positive foci (GGT foci) as an indicator of carcinogenicity. The by-products of disinfection, including chloramine, halogenated humic acids, halogenated ethanes, halogenated acetonitriles, halogenated methanes, halogenated ethylenes, and N-Cl-piperidine, did not initiate GGT foci, which would indicate that they are not capable of initiating carcinogenesis. Chloroform and halogenated benzenes were tested in this assay for their ability to promote the occurrence of GGT foci and tumors initiated by diethylnitrosamine (DENA). Chloroform (1800 ppm in the drinking water) either had no effect or inhibited the occurrence of GGT foci when administered subsequent to a single dose of DENA. However, when the chloroform was administered in drinking water concurrently with weekly doses of DENA, it enhanced the formation of liver tumors. Of 20 halogenated benzenes tested, only 1,2,4,5-tetrachlorobenzene and hexachlorobenzene promoted the occurrence of DENA-initiated GGT foci. Thus in rat liver, the tested by-products of drinking water disinfection did not demonstrate tumor-initiating activity, although a few appeared to possess tumor-promoting activity. Chloroform was also tested for tumor-promoting activity in 15-day-old Swiss mice initiated with ethylnitrosourea (ENU). At weaning they started to receive either 1800 ppm chloroform or 500 ppm sodium phenobarbital (the positive control for tumor promotion) in their drinking water. The mice continued to receive either chloroform or phenobarbital until 51 weeks of age and were sacrificed at 52 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)
17β-Estradiol inhibits Ca2+-dependent homeostasis of airway surface liquid volume in human cystic fibrosis airway epithelia
Authors: Ray D. Coakley, Hengrui Sun, Lucy A. Clunes, Julia E. Rasmussen, James R. Stackhouse, Seiko F. Okada, Ingrid Fricks, Steven L. Young, Robert Tarran
Journal: Journal of Clinical Investigation (2008)

Normal airways homeostatically regulate the volume of airway surface liquid (ASL) through both cAMP- and Ca2+-dependent regulation of ion and water transport. In cystic fibrosis (CF), a genetic defect causes a lack of cAMP-regulated CFTR activity, leading to diminished Cl- and water secretion from airway epithelial cells and subsequent mucus plugging, which serves as the focus for infections. Females with CF exhibit reduced survival compared with males with CF, although the mechanisms underlying this sex-related disadvantage are unknown. Despite the lack of CFTR, CF airways retain a limited capability to regulate ASL volume, as breathing-induced ATP release activates salvage purinergic pathways that raise intracellular Ca2+ concentration to stimulate an alternate pathway to Cl- secretion. We hypothesized that estrogen might affect this pathway by reducing the ability of airway epithelia to respond appropriately to nucleotides. We found that uridine triphosphate-mediated (UTP-mediated) Cl- secretion was reduced during the periovulatory estrogen maxima in both women with CF and normal, healthy women. Estrogen also inhibited Ca2+ signaling and ASL volume homeostasis in non-CF and CF airway epithelia by attenuating Ca2+ influx. This inhibition of Ca2+ signaling was prevented and even potentiated by estrogen antagonists such as tamoxifen, suggesting that antiestrogens may be beneficial in the treatment of CF lung disease because they increase Cl- secretion in the airways.
13 000 patients are at risk from meningitis in the US
Authors: E. Davies
Journal: BMJ (2012)

Up to 13 000 patients in 23 different states may have been exposed to fungal meningitis from tainted spinal steroid injections, the Centers for Disease Control and Prevention said.

The CDC confirmed that most of those affected had been contacted and were not ill but that the numbers could rise in the next few weeks from the 105 confirmed cases and …
A Longitudinal Study of Coronary Heart Disease
Authors: OGLESBY PAUL, MARK H. LEPPER, WILLIAM H. PHELAN, G. WESLEY DUPERTUIS, ANNE MACMILLAN, HARLLEY MCKEAN, HEEBOK PARK
Journal: Circulation (1963)

Certain of the data accumulated over the course of more than 4 years in a prospective study of coronary heart disease being carried on in an industrial population have been presented. In a base population of 1,989 men, 88 cases of coronary heart disease have developed: angina pectoris, 47 men; myocardial infarction, 28 men; death from coronary, disease, 13 men. This approximates one case per 100 men per year. The development of clinical coronary heart disease has shown an association with early age of death of father, history of "noncardiac" chest discomfort, history of chronic cough, history of shortness of breath, history of peptic ulcer, presence of increased skinfold thickness, elevated blood pressure, AV nicking in the fundi, elevated blood cholesterol, ST and T abnormalities in the electrocardiogram, and use of cigarettes and coffee. No relation was encountered between body weight, mean blood sugar levels, lipoprotein lipase levels, or diet (other than coffee), and the development of coronary heart disease. Similarly, there was no association with job type and no certain relation to physical activity off the job.
FACTORS ASSOCIATED WITH CARDIAC CONDUCTION DISORDERS AND PERMANENT PACEMAKER IMPLANTATION AFTER PERCUTANEOUS AORTIC VALVE IMPLANTATION
Authors: Ze Yie Yong, Jan Baan, Karel T. Koch, José P.S. Henriques, Berto J. Bouma, Marije M. Vis, Riccardo Cocchieri, Jan J. Piek, Bas A.J.M. de Mol
Journal: Journal of the American College of Cardiology (2010)
US House of Representatives approves historic healthcare reform bill
Authors: J. H. Tanne
Journal: BMJ (2010)

Increased urine albumin excretion is highly prevalent in Hispanics/Latinos. Previous studies have found an association between urine albumin excretion and Amerindian ancestry in Hispanic/Latino populations. Admixture between racial/ethnic groups creates long-range linkage disequilibrium between variants with different allelic frequencies in the founding populations and it can be used to localize genes. Hispanic/Latino genomes are an admixture of European, African, and Amerindian ancestries. We leveraged this admixture to identify associations between urine albumin excretion (urine albumin-to-creatinine ratio [UACR]) and genomic regions harboring variants with highly differentiated allele frequencies among the ancestral populations. Admixture mapping analysis of 12,212 Hispanic Community Health Study/Study of Latinos participants, using a linear mixed model, identified three novel genome-wide significant signals on chromosomes 2, 11, and 16. The admixture mapping signal identified on chromosome 2, spanning q11.2–14.1 and not previously reported for UACR, is driven by a difference between Amerindian ancestry and the other two ancestries (<i>P</i>&lt;5.7 × 10<sup>−5</sup>). Within this locus, two common variants located at the proapoptotic <i>BCL2L11</i> gene associated with UACR: rs116907128 (allele frequency =0.14; <i>P</i>=1.5 × 10<sup>−7</sup>) and rs586283 (C allele frequency =0.35; <i>P</i>=4.2 × 10<sup>−7</sup>). In a secondary analysis, rs116907128 accounted for most of the admixture mapping signal observed in the region. The rs116907128 variant is common among full-heritage Pima Indians (A allele frequency =0.54) but is monomorphic in the 1000 Genomes European and African populations. In a replication analysis using a sample of full-heritage Pima Indians, rs116907128 significantly associated with UACR (<i>P</i>=0.01; <i>n</i>=1568). Our findings provide evidence for the presence of Amerindian-specific variants influencing the variation of urine albumin excretion in Hispanics/Latinos.