tbuckley/cabot-search huggingface dataset:
Radical Radiation for Localized Prostate Cancer: Local Persistence of Disease Results in a Late Wave of Metastases
Authors: John J. Coen, Anthony L. Zietman, Harjot Thakral, William U. Shipley
Journal: Journal of Clinical Oncology (2002)

To assess whether failure to maintain local control (LC) of prostate cancer after radiation therapy results in a higher incidence of distant metastasis (DM).From 1972 to 1999, 1,469 patients with clinically localized prostate cancer were treated with radical radiation therapy. Disease outcome was retrospectively reviewed for all patients with more than 2 years of follow-up.The actuarial 10-year LC rate was 79%. Gleason score > or = 7, prostate-specific antigen (PSA) more than 15, and T3 to T4 tumors predicted a higher incidence of local failure (LF) (palpable recurrence or positive rebiopsy). The 10-year distant metastasis-free survival (DMFS) was 74%. Gleason score > or = 7, PSA more than 15, and T3 to T4 tumors predicted a higher incidence of distant failure. LF was the strongest predictor for DM in a multivariate model. The 10-year DMFS for LC and LF patients was 77% and 61%, respectively. Median time to distant failure was prolonged in patients with LF compared with patients with locally controlled disease (54 v 34 months). Hazard rate analysis of the time to DM revealed that patients who maintain LC have a lower rate of DM, which remains constant over time. Patients who ultimately develop LF have a higher initial rate of DM, which increases with time.Patients with locally persistent prostate cancer are at greater risk of DM. The higher initial hazard of DM is consistent either with an increased likelihood of subclinical micrometastases before treatment or with posttreatment tumor embolization. The prolonged time to appearance of DM in locally failing patients and the increasing hazard of DM over time is most consistent with a late wave of metastases from a locally persistent tumor.
ATPo but not cAMPi activates a chloride conductance in mouse ventricular myocytes
Authors: P. C Levesque, J. R Hume
Journal: Cardiovascular Research (1995)

The aim was to test for the presence of cAMPi activated and ATPo activated chloride conductances (ICl(cAMP) and ICl(ATP)) in mouse ventricular myocytes.Membrane currents were measured in enzymatically dissociated ventricular myocytes using the whole cell configuration of the patch clamp technique.After inhibiting the activation of sodium, calcium, and potassium currents, increasing [cAMP]i with isoprenaline (1 microM), forskolin (10 microM), or isobutylmethylxanthine (500 microM) had no effect on residual membrane current but extracellular ATP (100 microM) elicited a time independent background conductance. The ATP-activated conductance was observed during voltage steps ranging from +40 to -110 mV from a holding potential of -30 mV within 1 min after adding ATP to the bath. The reversal potential for the ATP activated conductance varied with changes in the chloride gradient and was within several mV of the predicted Nernst potential for chloride. Partially substituting external chloride with aspartate attenuated the ATP activated currents and shifted the reversal potential to values close to those predicted for ECl, suggesting the chloride selective nature of the conductance. The poorly hydrolysable ATP analogue ATP gamma S (100 microM) also elicited the chloride conductance, suggesting purinoceptor linked activation rather than a mechanism dependent on hydrolysis of ATP by ectoATPases. The conductance may be activated following P2 and not P1 purinoceptor stimulation, since the P1 purinoceptor agonists adenosine (500 microM) and adenosine monophosphate (500 microM) had no effect in seven and four cells, respectively. Activation of ICl(ATP) is not likely to be dependent on increased [Ca2+]i since ATP activated the current in cells dialysed with 10 mM EGTA or 20 mM BAPTA.(1) cAMPi does not activate a chloride conductance in mouse ventricular myocytes; (2) ATPo does activate a chloride conductance, through stimulation of a P2 purinoceptor; and (3) Ca2+i and cAMPi are not involved in activation of ICl(ATP). Also, macroscopic ICl(ATP) from mouse ventricle and ICl(cAMP) from other species appear to be indistinguishable in terms of time independence and rectification properties that depend on the concentration and permeability of intracellular anions. ICl(ATP) could be of physiological and pathophysiological significance considering the ability of chloride channels to modulate cardiac electrical activity and the fact that ATP may be an important neuromediator in the heart.
Unexpected danger of diazepam.
Authors: A Doughty
Journal: BMJ (1970)

demonstrated in small amounts.Liver func- tion tests on that day were as follows:Total bilirubin 1.1 mg./100 ml.; conjugated bilirubin 0-6 mg./ 100 ml.; alanine transaminase 60 I.U.; alkaline phosphatase 10 K.A. units; thymol turbidity 1; thymol flocculation 0; col- loidal gold 0.
Abt-Garrison History of Pediatrics
Authors: Lester S. King
Journal: JAMA (1965)

ABSTRACT Fielding H. Garrison was one of the pioneer American writers on medical history. With his vast knowledge of medical literature he presented salient historical details in straightforward sketches and expositions. But, while he set down facts, he paid relatively little attention to trends and movements—his writings constitute a chronicle rather than an interpretation, a reference book rather than an account of historical movement. His books do not convey any dramatic play of historical forces or the slow struggle of the new against the old. We miss a sense of historical development.The present volume reprints the history of pediatrics that Garrison originally wrote for the first volume of Pediatrics, edited by Isaac A. Abt. Since Garrison brought his chronicle only up to 1920, there would be very little point, in 1965, in simply reprinting the original monograph, unless it were done as a paperback. To be a working history of
828 TREATMENT WITH PEGINTERFERON ALFA-2A (40KD) AND RIBAVIRIN IN OLDER HCV GENOTYPE 1 PATIENTS WITH POSITIVE PROGNOSTIC FACTORS LEADS TO HIGH RATES OF SUSTAINED VIROLOGICAL RESPONSE
Authors: K.R. Reddy, D. Messinger, M. Popescu, S.J. Hadziyannis
Journal: Journal of Hepatology (2008)
Variability in purified dysfunctional C1(-)-inhibitor proteins from patients with hereditary angioneurotic edema. Functional and analytical gel studies.
Authors: V H Donaldson, R A Harrison, F S Rosen, D H Bing, G Kindness, J Canar, C J Wagner, S Awad
Journal: Journal of Clinical Investigation (1985)

C1(-)-inhibitor (C1(-)-INH) proteins from normal persons and members of eight different kindred with dysfunctional C1(-)-INH proteins associated with hereditary angioneurotic edema (HANE) were compared with respect to their inhibitory activity against purified preparations of C1s-, plasma kallikrein, activated forms of Hageman factor, and plasmin. Each dysfunctional C1(-)-INH protein showed a unique spectrum of inhibitory activity against these enzymes. Although none of the dysfunctional C1(-)-INH proteins significantly impaired amidolysis by plasmin, all but one inhibited activated Hageman factor. One purified dysfunctional C1(-)-INH (Ta) inhibited purified C1s- to a normal degree. Another C1(-)-INH (Za) had almost seven times as much inhibitory activity as normal C1(-)-INH against activated Hageman factor, but had decreased activity against C1s- and no activity against plasmin. Analyses of mixtures of plasmin and C1(-)-INH proteins in SDS gel electrophoresis revealed variability in the patterns of complex formation and cleavage of dysfunctional proteins after exposure to C1s- and plasmin. Some bound to plasmin and were cleaved, even though none significantly impaired the amidolytic activity of plasmin. Two were cleaved by C1s-, whereas neither normal or other dysfunctional C1(-)-INH were cleaved. Dysfunctional C1(-)-INH proteins from patients with HANE are thus heterogeneous in their inhibitory properties and there must be different structural requirements for the inhibition of the various plasma enzymes that can be regulated by normal C1(-)-INH. The data suggest that in addition to common sites of interactions between these proteases and C1(-)-INH, there are also points of contact that are specific for each protease. Genetic mutations leading to structural changes at some of these sites may have differing effects on the interaction between individual proteases and abnormal C1(-)-INH proteins. These alterations may allow these proteins to serve as probes for structural requirements for inhibitory actions of normal C1(-)-INH.
Vasodilator Therapy for Heart Failure: What Have We Learned From Controlled Clinical Trials?
Authors: Jay N. Cohn, Thomas S. Rector
Journal: JAMA (1988)

Vasodilator therapy has now gained wide acceptance as appropriate adjuvant drug treatment for congestive heart failure. Although this therapy previously was reserved for relief of persistent symptoms in patients who were already taking digitalis and diuretics, recent data have provided support for the concept that use of these drugs may prolong life in addition to relieving symptoms.<sup>1,2</sup>The evidence that systemic
Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis
Authors: Hai Wu, Troy W Whitfield, Jonathan A R Gordon, Jason R Dobson, Phillip W L Tai, Andre J van Wijnen, Janet L Stein, Gary S Stein, Jane B Lian
Journal: Genome biology (2014)

Abstract Background Osteogenesis is a highly regulated developmental process and continues during the turnover and repair of mature bone. Runx2, the master regulator of osteoblastogenesis, directs a transcriptional program essential for bone formation through genetic and epigenetic mechanisms. While individual Runx2 gene targets have been identified, further insights into the broad spectrum of Runx2 functions required for osteogenesis are needed. Results By performing genome-wide characterization of Runx2 binding at the three major stages of osteoblast differentiation - proliferation, matrix deposition and mineralization - we identify Runx2-dependent regulatory networks driving bone formation. Using chromatin immunoprecipitation followed by high-throughput sequencing over the course of these stages, we identify approximately 80,000 significantly enriched regions of Runx2 binding throughout the mouse genome. These binding events exhibit distinct patterns during osteogenesis, and are associated with proximal promoters and also non-promoter regions: upstream, introns, exons, transcription termination site regions, and intergenic regions. These peaks were partitioned into clusters that are associated with genes in complex biological processes that support bone formation. Using Affymetrix expression profiling of differentiating osteoblasts depleted of Runx2, we identify novel Runx2 targets including Ezh2, a critical epigenetic regulator; Crabp2, a retinoic acid signaling component; Adamts4 and Tnfrsf19, two remodelers of the extracellular matrix. We demonstrate by luciferase assays that these novel biological targets are regulated by Runx2 occupancy at non-promoter regions. Conclusions Our data establish that Runx2 interactions with chromatin across the genome reveal novel genes, pathways and transcriptional mechanisms that contribute to the regulation of osteoblastogenesis.
A holistic developmental theory requires better research techniques
Authors: George F. Michel
Journal: Behavioral and Brain Sciences (1999)

Research pragmatics, not a defective conceptual framework, supports modern biological reductionism. Conducting research to reveal the casual web underlying the multiple developmental pathways leading to any species-specific characteristic requires better research techniques than those commonly used. It takes much patience, time, and effort to gain even small glimpses of an answer to any developmental question.
A case of oral mucous membrane pemphigoid with IgG antibodies to integrin α6β4
Authors: S. Miyamoto, D. Chikazu, T. Yasuda, A. Enomoto, T. Oh-i, Y. Hirako, A. Tsuchisaka, A. Yasukochi, R. Sogame, K. Teye, H. Koga, N. Ishii, H. Qian, X. Li, T. Hashimoto
Journal: British Journal of Dermatology (2014)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Mucous membrane pemphigoid (MMP) presents various mucosal lesions, particularly velvety erythematous erosions along the teeth on the gingivae.1 2 Direct immunofluorescence reveals IgG and/or IgA deposits to the basement membrane zone (BMZ).1 In indirect immunofluorescence, IgG and/or IgA antibodies in 70–80% of MMP sera react with the epidermal side of 1 mol L−1 NaCl‐split skin, while IgG antibodies react with the dermal side in approximately 20% of MMP sera. In immunoblotting, IgG and/or IgA antibodies reactive with the epidermal side react with recombinant protein (RP) of the BP180 C‐terminal domain (anti‐BP180‐type MMP).3 4 5 IgG antibodies reactive with the dermal side react with laminin‐332 (antilaminin‐332‐type MMP).6 While anti‐BP180‐type MMP usually shows only oral lesions, antilaminin‐332‐type MMP tends to develop severe ocular and laryngeal lesions.1 In addition, previous studies reported that IgG antibodies to the β4 and α6 subunits of integrin α6β4 were detected in ocular and oral MMP, respectively.7 8 Thus, MMP is extremely heterogeneous, which makes diagnosis difficult. This study reports a patient with oral MMP with IgG autoantibodies to both the β4 and α6 subunits of integrin α6β4.
Monitoring nitrite, N-nitrosodiethanolamine, and mutagenicity in cutting fluids used in the metal industry.
Authors: S Monarca, G Scassellati Sforzolini, B Spiegelhalder, R Pasquini, C Fatigoni
Journal: Environmental Health Perspectives (1993)

We carried out an integrated environmental/biological monitoring program to evaluate cancer hazards among metal industry workers exposed to cutting fluids. Several cutting fluids were sampled according to response to a semiquantitative nitrite rapid test in metal factories in central Italy. The nitrite-positive samples were analyzed for nitrite and nitrosodiethanolamine (NDELA) content and mutagenic activity. The nitrite-negative samples were analyzed only for mutagenicity. Of the total samples, 20.6% were nitrite positive, and all contained NDELA. However, nitrite content was not quantitatively predictive of the NDELA content, which varied enormously among samples (0.3-1900 mg/kg). Nitrite-negative samples were always nonmutagenic. Mutagenicity was found in half the NDELA-containing samples but was not related to nitrite or NDELA content. Nitrite screening of cutting fluids in the field is an interesting method for identifying samples that potentially contain NDELA and other unknown mutagens and, when performed with short-term mutagenicity tests, nitrite screening seems to be a valid tool by which industrial managers and health officers could minimize the health hazards associated with occupational exposure to cutting fluids.
Inquiry is needed into difficulties of developing academic careers
Authors: B. M Ogilvie
Journal: BMJ (1996)

but zygosity has no effect on the risk of disease for either male (P=0-23) or female twins (P=0-63).John A Davis's points about environmental factors such as infection and diet are important.In fact, in our paper we argued against uncritical use of estimates of heritability and for in depth studies of concordance according to zygosity and the co-occurrence of immunological markers and susceptibility genes.Davis's points about monozygotic twins being reared differently from dizygotic twins and being of a lower birth weight would imply a higher prevalence of disease in monozygotic than dizygotic twins.However, we have found exactly the same prevalence of disease in monozygotic and dizygotic twins, similar to that in the general population.
BIOLOGICAL ACTIVITY OF THE CLEAVAGE PRODUCT OF HUMAN IMMUNOGLOBULIN G WITH CYANOGEN BROMIDE
Authors: Mira Lahav, Ruth Arnon, Michael Sela
Journal: The Journal of Experimental Medicine (1967)

Treatment of human IgG with cyanogen bromide in 0.05 M HCl under specified conditions resulted in the cleavage of about half of its methionyl peptide bonds. A major fragment of about 5S was isolated from the reaction mixture by gel filtration in quantitative yield. The CNBr fragment reacted fully with goat antiserum against human light chain, but its reaction with anti-heavy chain was markedly decreased. The treatment with CNBr caused a drastic decrease in the following biological activities of IgG: complement fixing, skin binding, reaction with antiglobulin factors, and reaction with specific anti-Gm(12) serum. On the other hand, the reaction with serum of anti-Gm(1) or anti-Gm(4) specificity was not impaired and antibody activity, namely antistreptolysin and isohemagglutinin, was retained after the treatment with CNBr. It is concluded that the CNBr cleaves preferentially the methionyl bonds in the Fc portion of IgG, and that the major fragment obtained, denoted F(ab'')(2), has still the combining properties of a divalent antibody. The possible therapeutic uses of F(ab'')(2) are discussed.
Abstract B07: Metabolic liabilities of human colon carcinoma spheroids are different compared to standard 2D cultures
Authors: Brian P. Dranka, Pamela Swain, George W. Rogers, Ajit S. Divakaruni, Andy Neilson, David A. Ferrick
Journal: Cancer Research (2015)

Abstract The search for metabolic liabilities in tumor cells is typically performed in standard 2D cultures. This approach lacks the 3D context and heterogeneity of tumor tissue in vivo, which has significant impact on their metabolic behavior. One solution to modeling complex tumor cell interactions is to use cultured tumor spheroids. To assess bioenergetic function in individual spheroids, a modified, 96-well plate for the Seahorse Bioscience XFe96 Extracellular Flux Analyzer was created. Here, we demonstrate the capability of measuring mitochondrial oxygen consumption – a measure or mitochondrial respiration – and extracellular acidification – a measure of glycolytic flux – in individual HCT116 colon carcinoma spheroids. Spheroids were cultured using the hanging drop method for 4 days. Mitochondrial function was determined using the Cell Mito Stress Test which profiles 6 specific indices of mitochondrial activity. Cells grown in spheroids had a markedly increased spare respiratory capacity compared to cells in 2D culture. These data are consistent with a shift from the highly proliferative nature of 2D culture to a more physiological model where proliferation and differentiation is more balanced. We hypothesize that viewing metabolism holistically allows for a more complete view of cellular bioenergetic function and potential liabilities. To understand the metabolic potential of cells in the context of their basal metabolism, two new metrics for describing mitochondrial function were established. By stimulating maximal oxygen consumption by combined exposure to oligomycin and FCCP, and maximal extracellular acidification rate (ECAR) using rotenone, antimycin A, and oligomycin, the potential to switch metabolic pathways was determined. Metabolic Capacity Index was identified using the maximal responses in each direction, and Metabolic Flexibility Index was calculated as the angle of the line to identify cellular preference for OXPHOS or glycolysis. Interestingly, plastic-adherent HCT116 cells only exhibited potential to increase glycolysis, while HCT116 spheroids had a more balanced response. These data are consistent with the finding that spheroids have increased spare capacity. Implications of this work for future studies in cancer biology will be discussed. Citation Format: Brian P. Dranka, Pamela Swain, George W. Rogers, Ajit S. Divakaruni, Andy Neilson, David A. Ferrick. Metabolic liabilities of human colon carcinoma spheroids are different compared to standard 2D cultures. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B07. doi:10.1158/1538-7445.CHTME14-B07
Indian Supreme Court rejects bid for panel to be established to regulate soft drinks
Authors: M. Kay
Journal: BMJ (2013)

India’s Supreme Court has rejected a public interest lawsuit asking that an independent expert committee be set up to evaluate the effects of soft drinks on human health and, in particular, on children’s health.

The suit was filed by the Centre for Public Interest Litigation, a non-governmental organisation that conducts litigation on matters of public interest.

The suit also demanded a regulatory regime that could check for and control the addition of particular chemical additives to foods, including soft drinks.

The court said that the existing legislation had provisions to check the risks to health of contaminants and chemical additives in food and thus that a separate entity was not needed.

The judgment passed …
GASTRO-JEJUNOSTOMY FOR STENOSIS OF PYLORUS—POSTMORTEM SIX YEARS LATER.
Authors: A. H. CORDIER
Journal: JAMA (1902)

Mr. C., aged 38, eighteen years ago began having digestive trouble. It was noticed at that time that solid particles of food in the stomach gave rise to more or less pain. A year or so later, vomiting began as a symptom. This vomiting was usually produced by the presence of food in the stomach. After the stomach was emptied the pain would cease, and the patient would be fairly comfortable until after another meal. On one or two occasions he had quite a perceptible show of fresh blood in the vomited material. This condition of painful digestion continued up to the time of my first examination. In addition to the above history I learned from the patient that large quantities of material would be thrown up that had been retained in the stomach for two or three days. As much as twelve or fourteen pounds of strongly acid, offensive
Absence of Gallium-67 Avidity in Diffuse Pulmonary Calcification
Authors: MYRON L. LECKLITNER, RICHARD W. FOSTER
Journal: Clinical Nuclear Medicine (1985)

Diffuse pulmonary uptake by bone-seeking radiopharmaceuticals has been reported previously but, in the same patient, would pulmonary uptake of Ga-67 citrate yield clinically meaningful results? A patient with hypercalcemia and renal failure in whom bone scintigraphy demonstrated striking diffuse bilateral pulmonary uptake, but subsequent gallium imaging demonstrated no evidence of pulmonary uptake greater than body background, is discussed. We conclude that pulmonary uptake of gallium cannot be attributed to calcium deposition and should carry the same clinical significance in regard to inflammatory and malignant lesions as would be assigned to patients without pulmonary calcific deposits.
Environmental factors differentially influence the persistence or remission of infantile wheezing during the first three years of life*1
Authors: G.E. Akan, J.E. Gern, Z. Li, M.D. Evans, K.A. Roberg, C.J. Tisler, R.E. Gangnon, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2004)
Reversal of Acute Exacerbations of Chronic Obstructive Lung Disease by Inspiratory Assistance with a Face Mask
Authors: Laurent Brochard, Daniel Isabey, Jacques Piquet, Piedade Amaro, Jorge Mancebo, Amen-Allah Messadi, Christian Brun-Buisson, Alain Rauss, François Lemaire, Alain Harf
Journal: New England Journal of Medicine (1990)

Patients with acute exacerbations of chronic obstructive pulmonary disease may require endotracheal intubation with mechanical ventilation. We designed, and here report on the efficacy of, a noninvasive ventilatory-assistance apparatus to provide inspiratory-pressure support by means of a face mask.