tbuckley/cabot-search huggingface dataset:
A3.9 DOT1L, a H3K79 methyltransferase linked to the WNT signallingsignaling cascade, regulates fibrotic responses in lung fibroblasts
Authors: C Aznar-Lopez, E De Langhe, S Monteagudo, F Cailotto, RJ Lories
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Fibrosis is the formation of excess fibrous connective tissue. It disturbs cell, tissue and organ homeostasis, leading to severe disease manifestations in various disorders. Transcriptional regulation of genes and pathways with pro- or anti-fibrotic effects is therefore a therapeutic target. DOT1-like histone H3 methyltransferase (DOT1L) is the only known H3K79 methyltransferase. It functions as a positive mediator of gene transcription, of DNA repair, as a regulator of the cell cycle, and has been associated with Wnt signalling. Our aim is to study the role of DOT1L in downstream events associated with pro-fibrotic cascades, hypothesising that it may act as an epigenetic masterswitch in the fibrotic process. <h3>Materials and methods</h3> MRC5 cells (a human fetal lung fibroblast cell line) were cultured for up to 22 days with 0 and 3µM of EPZ04777 (DOT1L inhibitor). During that period, the cells were stimulated at different time-ponts, with 0 to 5 ng/mL TGFβ<sub>1</sub> for 24 h. We performed mRNA and protein expression analysis. Total RNA was extracted from cell lysates and reverse-transcribed, and gene expression levels were quantified with real-time quantitative PCR (qPCR). Expression was normalised to <i>Hprt</i> and subsequently normalised to the vehicle condition using the comparative cycle threshold method (ΔΔCT). Total cell lysates were homogenised in Cell Extraction Buffer and proteins were analysed by immunoblot, including assessment of the H3K79 methylation status. <h3>Results</h3> Long-term treatment progressively decreases the methylation status of H3K79. Upon stimulation with TGFβ1, MRC5 cells show upregulation of type I Collagen mRNA expression and collagen deposition. Moreover, αSMA mRNA expression is also increased, indicating a fibroblast to myofibroblast differentiation. TGFβ1 stimulation also increased DOT1L expression and activity in the absence of EPZ04777, as shown by qPCR and H3K79 methylation status. Upon treatment with EPZ04777, we also observed an increase in collagen and αSMA expression, suggesting that loss of DOT1L activity results in pro-fibrotic changes in lung fibroblasts. <h3>Conclusions</h3> DOT1L has homeostatic effects in the healthy lung fibroblast, since its inhibition triggers a pro-fibrotic transcriptional response. Its upregulation by TGFβ1 could represent a regulatory feedback loop that requires further investigation.
Effects of Antimetabolites upon the Renewal Patterns of Normal Cells.
Authors: Joseph Post
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Effects of Antimetabolites upon the Renewal Patterns of Normal Cells.Joseph Post, M.D., F.A.C.P., Joseph Hoffman, M.D., (Associate)Joseph Post, M.D., F.A.C.P.Search for more papers by this author, Joseph Hoffman, M.D., (Associate)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-798_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptClinical experience has shown that the use of antimetabolites in the treatment of cancer and as immunosuppressants is limited by the tolerance of the host for the destruction of replicating hematopoietic and gut cells. Previous in vivo studies from this laboratory have correlated these effects with the more rapid multiplication of the normal populations vis-à-vis the coexistent autogenous tumor cells (New Eng J Med279:248, 1968; National Cancer Institute Monograph No. 30, p. 209, 1969). This report deals with the effects of nitrogen mustard and methotrexate, administered at sublethal dose levels, upon the renewal patterns of coexistent ileal cells and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Joseph Post, M.D., F.A.C.P.; Joseph Hoffman, M.D., (Associate)Affiliations: New York, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 798-798KeywordsCancer immunotherapyCancer treatmentCellsImmunosuppressivesMethotrexatePopulation statisticsResearch laboratories ePublished: 1 December 2008 Issue Published: 1 May 1970 PDF downloadLoading ...
Gastropericardial Fistula after Laparoscopic Surgery for Reflux Disease
Authors: Sudish Murthy, John Looney, Michael T. Jaklitsch
Journal: New England Journal of Medicine (2002)

When patients with severe gastroesophageal reflux disease require surgery, the operation is frequently performed through a laparoscope. This case report describes a life-threatening gastropericardial fistula, which was a late complication of a laparoscopic Nissen fundoplication, as well as its repair.
Follow-up of Patients With Breast Cancer
Authors: U. Yun Ryo
Journal: JAMA (1994)

To the Editor.  —The studies published recently by the GIVIO Investigators 1 and by Rosselli Del Turco et al 2 are timely and well intended. However, the conclusions drawn by the investigators might be misleading.  The conclusion reached by the GIVIO group is that the health-related quality of life of breast cancer patients was the same whether follow-up examinations were performed with or without imaging procedures and laboratory tests. This conclusion was based on responses to questionnaires; 68% (901 of 1320) at 1 year, and 60% (639 of 1066 survivors) at the fifth year. Forty percent of the subjects did not respond to the questionnaires or were not included in the fifth-year survey. What if those nonresponders in the fifth year have a completely different sense of well-being?  Patients with breast cancer in the early stages, similar to the subjects in the two studies, may show a disease-free survival of
Lower Endogenous Androgen Levels and Dyslipidemia in Men with Non-Insulin-Dependent Diabetes Mellitus
Authors: Elizabeth Barrett-Connor
Journal: Annals of Internal Medicine (1992)

To compare plasma androgen levels in diabetic and nondiabetic men and to determine their relation to diabetic dyslipidemia.A population-based, case-control study.Community.Men 53 to 88 years of age from the Rancho Bernardo, California, cohort who were screened for diabetes using an oral glucose tolerance test.Plasma androgen levels were compared in 44 men with untreated non-insulin-dependent diabetes mellitus and 88 age-matched men who had a normal glucose tolerance test. The relation of lipid and lipoprotein levels to androgen level and diabetic status was assessed before and after adjusting for covariates.Men with diabetes had significantly lower plasma levels of free (4.96 nmol/L compared with 5.58 nmol/L) and total testosterone (14.7 nmol/L compared with 17.4 nmol/L), dihydrotestosterone (428 pg/mL compared with 533 pg/mL), and dehydroepiandrosterone sulfate (DHEA-S) (1.92 mumol/L compared with 2.42 mumol/L) than nondiabetic men. They also had significantly lower high-density lipoprotein (HDL) cholesterol and significantly higher triglyceride levels. Differences were not explained by obesity, alcohol use, or cigarette habit. Overall, the total testosterone level, but not the free testosterone level, was positively correlated with the HDL cholesterol level (P = 0.009) and negatively correlated with the triglyceride level (P = 0.0001). Similar associations were seen in analyses restricted to the men without diabetes.Lower levels of endogenous androgens are seen in older diabetic men, and low androgen levels are associated with diabetic dyslipidemia.
Abstract 1921: Mutational and expressional analyses of <i>DICER1</i> gene in ovarian stromal tumors and other common tumors.
Authors: Min Sung Kim, Eun Mi Je, Youn Jin Choi, Nam Jin Yoo, Sug Hyung Lee
Journal: Cancer Research (2013)

Abstract Recurrent missense somatic mutations in DICER1 gene affecting exons 25 and 26 have recently been reported in non-epithelial tumors of ovary, especially in Sertoli-Leydig cell tumors (SLCT). Such a recurrent nature of the mutations strongly suggests that DICER1 mutation may play an important role in the development of ovarian non-epithelial tumors. The aim of this study was to further characterize the DICER1 mutations in human tumor tissues. We analyzed the DICER1 mutations in 2,819 tumor tissues from ovary and other organs by single-strand conformation polymorphism analysis. We found the DICER1 exon 25 and 26 hot-spot mutations in 2 of 14 SLCT (14.3%) and one of 132 non-Hodgkin lymphomas (0.8%), but none in other tumors. In SLCT, DICER1 expression was observed in Sertoli cells, but neither in Leydig nor spindle-shaped cells. We also analyzed DICER1 expression in lung, stomach, colon and prostate cancer tissues. DICER1 expression was lost in 37% of prostate cancers, but not in lung, stomach and colon cancers. Our data indicate that DICER1 recurrent mutations commonly occur in SLCT, but the incidence was significantly lowerthan that in the earlier study. Our data suggest that both DICER1 mutation and its expression loss may be important in tumor pathogenesis and that they are tumor type-specific. Citation Format: Min Sung Kim, Eun Mi Je, Youn Jin Choi, Nam Jin Yoo, Sug Hyung Lee. Mutational and expressional analyses of DICER1 gene in ovarian stromal tumors and other common tumors. [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 1921. doi:10.1158/1538-7445.AM2013-1921
63 Intranasal fluticasone propionate (FP) is more effective than loratadine (LOR) for treatment of seasonal allergic rhinitis symptoms
Authors: A NAYAK, D SHULAN, D BERNSTEIN, M LIVEZEY, G SETTIPANE, P CHERVINSKY, J MELAMED, J SELCOW, K REED, G ANSCHUETZ
Journal: Journal of Allergy and Clinical Immunology (1996)
Twenty one years of legal abortion
Authors: R. Balfour
Journal: BMJ (1989)

incidence of myocardial infarction are related to social class.It would have been sensible to match cases and controls for social class as well as for age and sex.Dr Mattila and colleagues went to great lengths to discount social class as a confounding variable, including the use of logistic regression, but they did not include a table to compare the dental indexes for cases and controls within each social class, which would have been very informative.The two methods of assessing dental health are innovative, to say the least, and neither is referenced.The total dental index and the pantomography index included measurements of both caries and periodontal disease.It is more appropriate and more usual to examine for factors associated with caries, a disease predominantly related to diet, with the DMF (delayed, missing, and filled teeth) index,2 and to measure periodontal disease, traditionally related to oral hygiene and age, with the community periodontal index of treatment need (CPITN index).'Whatever index ofdental health is used, it should have been applied by. a single, blinded observer.There are also several misuses of statistics in the paper.Dr Mattila and colleagues claimed that the "high correlation" (r=069) between the pantomography index (which was assessed blind) and the total dental index (which was not) suggests that the total dental index assessment was not biased.The use of correlation is not appropriate in this context,4 nor in assessing the strength of the association between the total dental index and a discrete variable such as social class.In view of these.design flaws, we remain unconvinced of the clinical relevance of the observed association between poor dental health and myo- cardial infarction, which can probably be explained by study bias or, more possibly, by the known association of low social class with both disorders.
EXPERT TESTIMONY IN DISPUTED CASES OF INEBRIETY.
Authors: T. D. CROTHERS
Journal: JAMA (1896)

During the past year several very important cases have brought out the most widely divergent expert testimony, clearly showing the need of new study of this subject. Disputed cases of inebriety are increasing every year. Not the petty contests of police and criminal courts, where the questions raised are technical for partisan purposes, but facts of great interest and profound questions of science on which large issues turn. In one case, the final disposition of over a million dollars turned on the question of the normal condition of the mind of a testator who used spirits to excess. In another case a forgery which implicated many persons, depended on the judgment of experts relating to the motives of an inebriate. Several murder and homicidal cases have been disposed of on the testimony of medical experts. The final issue of all these cases has been the subject of divergent views in
Former police doctor is suspended after a death in custody
Authors: C. Dyer
Journal: BMJ (2014)

A former police doctor has been suspended from practice for 12 months by the Medical Practitioners Tribunal Service (MPTS) for failing to examine a homeless man with a head injury who was unconscious in a cell before declaring that he was fit to be detained.

Hisham El-Baroudy spent no more than one minute in the cell with Andrzej Rymarczak at Chelsea police station in …
On the mechanism of lysophosphatidylcholine-induced depolarization of cat ventricular myocardium.
Authors: C W Clarkson, R E Ten Eick
Journal: Circulation Research (1983)

Lysophosphatidylcholine, a putative biochemical mediator of ischemia-induced arrhythmias, reduces the resting potential of ventricular muscle. To elucidate possible mechanisms of lysophosphatidylcholine-induced depolarization, we investigated the effects of lysophosphatidylcholine on the electrophysiological properties of cat ventricular muscle, using potassium ion-selective electrodes and conventional microelectrode, current-, and voltage-clamp techniques. Lysophosphatidylcholine (50 microM) decreased the sensitivity of the resting potential to changes in extracellular potassium concentration. Hyperpolarization of lysophosphatidylcholine-depolarized fibers by current-clamp methods failed to reveal two stable levels of resting potential. Depolarizing concentrations of lysophosphatidylcholine did not reduce the potassium equilibrium potential, as determined from the reversal potential of the time-dependent potassium current and measurements of intracellular potassium activity using potassium ion-selective electrodes. Lysophosphatidylcholine induced a depolarizing shift of the reversal potential for steady state current, and did not induce the formation of a negative slope region in the steady state current-voltage or background current-voltage relationships. Lysophosphatidylcholine induced an inward shift and linearization of the background current-voltage relationship negative to -30 mV, and the lysophosphatidylcholine-sensitive component of the background current was an inward rectifier with a reversal potential approximately equal to the potassium equilibrium potential. Lysophosphatidylcholine also reduced the amplitudes of the time-dependent potassium current, slow inward current, and the potassium accumulation and depletion currents. These results indicate that lysophosphatidylcholine-induced depolarization is due, in part, to reduced potassium conductance at voltages near the normal resting potential, and that lysophosphatidylcholine may act as a nonspecific depressant of membrane channels.
Mathematics Recovered for the Natural and Medical Sciences
Authors: Bruce B. Dan
Journal: JAMA (1992)

Did you learn the quadratic formula in high school but now can't remember it? Have you forgotten whether the secant is the inverse of the sine or cosine? Is it impossible to recollect how many combinations there are of six things taken two at a time? Well, if all you remember about making an eight the hard way is that it pays off big in Vegas, then Britisher Dennis Rosen's paperback may be just the solution to recover that pair of dice lost. Rosen, an instructor in biophysics at Birbeck College, University of London, is interested in helping fellow scientists who can separate a grasshopper from a mantis, but not a characteristic from a mantissa. While this digest is most useful as a quick reference text for those who have chosen a biomedical career, each section includes examples and exercises for students as well. The 15 chapters begin simply enough
110 No recurrence in patients transplanted for YMDD genotypic mutations using pre-emptive lamivudine followed by combination prophylaxis
Authors: L. Caccamo, R. Romeo, L.S. Belli, M. Vangeli, G. Rossi, A.B. Alberti, G. Pinzello, M. Colombo, L.R. Fassati
Journal: Journal of Hepatology (2004)
ANALYSIS OF INFLAMMATION
Authors: Geert W. Schmid-Schönbein
Journal: Annual Review of Biomedical Engineering (2006)

In the past, inflammation has been associated with infections and with the immune system. But more recent evidence suggests that a much broader range of diseases have telltale markers for inflammation. Inflammation is the basic mechanism available for repair of tissue after an injury and consists of a cascade of cellular and microvascular reactions that serve to remove damaged and generate new tissue. The cascade includes elevated permeability in microvessels, attachment of circulating cells to the vessels in the vicinity of the injury site, migration of several cell types, cell apoptosis, and growth of new tissue and blood vessels. This review provides a summary of the major microvascular, cellular, and molecular mechanisms that regulate elements of the inflammatory cascade. The analysis is largely focused on the identification of the major participants, notably signaling and adhesion molecules, and their mode of action in the inflammatory cascade. We present a new hypothesis for the generation of inflammatory mediators in plasma that are derived from the digestive pancreatic enzymes responsible for digestion. The inflammatory cascade offers a large number of opportunities for development of quantitative models that describe various aspects of human diseases.
Assumptions and extrapolation
Authors: S. Bangalore, F. H Messerli
Journal: BMJ (2009)

Law and colleagues’ conclusion, that blood pressure should be lowered in everyone over a certain age, rather than measured in everyone and treated in some, is derived from 147 disparate trials.1 The trials have varying inclusion/exclusion criteria, and were conducted in patients aged 34-84, with follow-up of 0.5-8.4 years, and in those with hypertension, after myocardial infarction, with coronary artery disease without myocardial infarction, and with heart failure. …
Different Compartments of Sarcoplasmic Reticulum Participate in the Excitation-Contraction Coupling Process in Human Atrial Myocytes
Authors: Stephane N. Hatem, Agnes Benardeau, Catherine Rucker-Martin, Isabelle Marty, Patricia de Chamisso, Michel Villaz, Jean-Jacques Mercadier
Journal: Circulation Research (1997)

The excitation-contraction coupling process of human atrial myocytes was studied in voltage-clamped myocytes isolated from right atrial appendages obtained during cardiac surgery. Intracellular Ca2+ transients (Cai transients) were monitored with 0.1 mmol/L indo 1 added to the internal dialyzing solution. Ryanodine receptors (RyRs) and sarcomeric alpha-actinin were stained with specific antibodies and visualized using plane and confocal microscopy. L-Type Ca2+ current (Ica) elicited a prolonged Cai transient, with an initial rapidly activating phase (slope 1, 23.6 +/- 1.2 s-1) followed by a slowly activating phase (slope 2, 5.8 +/- 0.4 s-1; P < .001 versus slope 1), resulting in a dome-shaped Cai transient. Ryanodine (100 mumol/L) inhibited 79 +/- 6% of the Cai transient, indicating that it was due essentially to sarcoplasmic reticulum Ca2+ release. During step depolarizations, maximal activation of the Cai transient or tail current (Itail) (in cells dialyzed with Ca2+ buffer-free internal solution) preceded that of Ica and did not follow its voltage dependence (n = 12). Test pulses lasting from 5 to 150 milliseconds elicited a similar time course of both Cai transient and Itail (n = 5). In a given cell, the two components of the Cai transient could be dissociated by altering the intracellular Ca2+ load, by increasing the stimulation rate from 0.1 to 1 Hz, or by varying the amplitude of Ica. Immunostaining of atrial sections and isolated myocytes showed that a large number of RyRs were located not only in a subsarcolemmal position but also deeper inside the cell, in a regularly spaced transverse band pattern at the level of Z lines. Together, our results indicate that, in human atrial myocytes, Ica only partially controls the activation of RyRs, with the prolonged and dome-shaped Cai transient of these cells probably reflecting the activation of RyRs not coupled to L-type Ca2+ channels.
Serial assessment of left ventricular mass regression by 3D echocardiography requires three-fold fewer subjects compared to conventional 1D and 2D echocardiography
Authors: Aasha S. Gopal, Matthew J. Schnellbaecher, Zhanqing Shen, Robert R. Sciacca, Andrew M. Keller, Peter M. Sapin, Donald L. King
Journal: Journal of the American College of Cardiology (1996)
The other estrogen receptor in the plasma membrane: implications for the actions of environmental estrogens.
Authors: C S Watson, T C Pappas, B Gametchu
Journal: Environmental Health Perspectives (1995)

Environmental or nutritional estrogenic toxicants are thought to mediate developmental and carcinogenic pathologies. Estrogen receptor (ER) measurements are currently used to predict hormonal responsiveness; therefore all ER subpopulations should be considered. We have been involved in the immunoidentification and characterization of membrane steroid receptors in several systems and have recently shown that binding of estradiol (E2) to a subpopulation of ERs (mER) residing in the plasma membrane of GH3 pituitary tumor cells mediates the rapid release of prolactin (PRL). Here we review these findings and present other important characterizations of these receptors such as trypsin and serum susceptibility, movement in the membrane, confocal localization to the membrane, binding to and function of impeded ligands, and immunoseparation of cells bearing mER. We plan to use this system as a model for both the physiological and pathological nongenomic effects of estrogens and estrogenic xenobiotics. Specifically, it should be useful as an in vitro assay system for the ability of estrogenic xenobiotics to cause rapid PRL release as an example of nongenomic estrogen effects.