tbuckley/cabot-search huggingface dataset:
S129 Decreased cAMP Production in Lung Fibroblasts from Patients with Idiopathic Pulmonary Fibrosis
Authors: RL Simms, WR Coward, AJ Knox, L Pang
Journal: Thorax (2012)

<h3>Rationale</h3> Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with unknown aetiology and no effective therapy. Myofibroblasts are the primary effector cells in the pathogenesis of IPF and differentiation from fibroblasts is a major source of myofibroblasts. Prostaglandin E2 (PGE<sub>2</sub>) inhibits fibroblast to myofibroblast differentiation via the E Prostanoid 2 (EP2) receptor and cAMP, suggesting cAMP is a key regulator of myofibroblast differentiation. The aim of the present study was to evaluate the effect of different cAMP elevating agents on myofibroblast differentiation. <h3>Methods</h3> Fibroblasts from lungs of patients with IPF (F-IPF) and from non-fibrotic lungs (F-NL) were used. TGF-β1 (2ng/ml 3d) was used to induce myofibroblast differentiation. The effect of PGE2, β2-agonists Salmeterol and Formoterol, the direct adenylyl cyclase activator Forskolin and the phosphodiesterase 4 (PDE4) inhibitor Roflumilast (all 1µm, 3d) was evaluated. IL-1β (2ng/ml, 24hr) was used for cyclooxygenase 2 (COX-2) induction. α-smooth muscle actin (α-SMA, a myofibroblast marker), COX-2, EP2, EP4 and β2-receptor expression was analysed by Western blotting and immunocytochemistry, respectively. Adenylyl cyclase mRNA was measured by qPCR and cAMP was measured by radioimmunoassay. <h3>Results</h3> F-IPF showed increased α-SMA and collagen expression and repressed COX-2 expression compared to F-NL. PGE2 treatment prevented TGF-β1-induced α-SMA expression and COX-2 repression in F-NL, which was mimicked by β2-agonists and Forskolin. PGE2 also reduced α-SMA expression and increased COX-2 expression in F-IPF despite that it induced significantly less cAMP than in F-NL But this effect on F-IPF was not mimicked by β2-agonists and Forskolin as they induced even less cAMP than PGE2 in these cells. TGF-β-treated F-NL also produced less cAMP than untreated cells in response to these cAMP. stimulants. However, the expression of EP2, EP4, β2-adrenoceptors and adenylyl cyclase isoforms was similar in F-NL and F-IPF. Furthermore, combination of PGE2 with Roflumilast showed greater effect than PGE2 alone on α-SMA reduction and COX-2 expression in F-IPF and F-NL, whereas Roflumilast alone had no effect. <h3>Conclusions</h3> cAMP is a key anti-fibrotic regulator of myofibroblast differentiation. However, cAMP production in myofibroblasts is defective, probably due to increased degradation by PDE4.
Abstract 2068: Opposite effects of arsenic trioxide on the Nrf2 pathway in oral squamous cell carcinoma <i>in vitro</i> and <i>in vivo</i>
Authors: Xinyan Zhang, Ying Su, Min Zhang
Journal: Cancer Research (2012)

Abstract Nuclear factor erythroid derived like 2 (Nrf2) is a critical transcriptional factor in mediating cellular defense mechanisms against oxidative stress or electrophiles. Arsenic has been reported to induce malignant transformation of human cells through Nrf2-dependent signaling pathway. However, arsenic is also a promising cancer therapeutic drug for solid tumors, including oral squamous cell carcinoma (OSCC). It is still unclear how Nrf2 may mediate cellular response of OSCC cells when treated with arsenic. In order to fully understand the impact of Nrf2 signaling in human OSCC, we examined expression of Nrf2 and Nrf2-regulated genes in arsenic trioxide (ATO) treated OSCC cells in vitro and in ATO-treated OSCC xenografts. ATO exerted its anti-tumor effects on both cultured OSCC cells and OSCC xenografts by inhibiting cell growth, suppressing angiogenesis and inducing apoptosis. ATO activated a silent Nrf2 pathway in cultured OSCC cells as shown by induction of Nrf2 and Nrf2-regulated genes, NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), in a dose-dependent manner. On the contrary, Nrf2 pathway became active in OSCC xenograft tumors, and ATO treatment down-regulated expression of Nrf2 and Nrf2-regulated genes. Our study clearly demonstrated opposite effects of ATO on Nrf2 pathway in OSCC in vitro and in vivo. 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 2068. doi:1538-7445.AM2012-2068
Acute occupational disinfectant-related illness among youth, 1993-1998.
Authors: Theresa A Brevard, Geoffrey M Calvert, Jerome M Blondell, Louise N Mehler
Journal: Environmental Health Perspectives (2003)

Working youths face many safety and health risks. Among these risks are those posed by disinfectant exposures. In this study we describe acute occupational disinfectant-related illness among youth. Data on U.S. children younger than 18 years with acute occupational disinfectant-related illnesses between 1993 and 1998 were collected from the Toxic Exposure Surveillance System and from the California Department of Pesticide Regulation. We analyzed data from persons with exposures who met the case definition for acute occupational disinfectant-related illness. The case definition required onset of new adverse health effects that were both temporally related to a disinfectant exposure and consistent with the known toxicology of the disinfectant. We calculated incidence rates of acute occupational disinfectant-related illness among youths 15-17 years old and incidence rate ratios to compare these rates with those of adults 25-44 years old. We found 307 children with disinfectant-related illnesses. The average annual incidence rate was 16.8/billion hours worked with a relative risk compared with adults of 4.14 (95% confidence interval, 3.66-4.68). Most illnesses were of mild severity (78%). There were no fatalities. Hypochlorites (e.g., bleach) were responsible for 45% of the illnesses. Among the 206 cases where the responsible disinfectant's U.S. Environmental Protection Agency toxicity category was known, 80% were in category I (highest toxicity level). These findings suggest the need for greater efforts to prevent adolescent acute occupational disinfectant-related illness. This may require strengthening regulations and enforcement as well as increased educational efforts directed at employers, youths, parents, school officials, and physicians. Better mechanisms for reporting and tracking chemical illnesses among working adolescents are also needed.
Cidofovir: A Novel Antitumor Agent for Glioblastoma
Authors: Piotr Hadaczek, Tomoko Ozawa, Liliana Soroceanu, Yasuyuki Yoshida, Lisa Matlaf, Eric Singer, Estefania Fiallos, C. David James, Charles S. Cobbs
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Cidofovir (CDV) is an U.S. Food and Drug Administration (FDA)-approved nucleoside antiviral agent used to treat severe human cytomegalovirus (HCMV) infection. Until now, no clear therapeutic effects of CDV have been reported outside of the setting of viral infection, including a potential role for CDV as an antineoplastic agent for the treatment of brain tumors. Experimental Design: We investigated the cytotoxicity of CDV against the glioblastoma cells, U87MG and primary SF7796, both in vitro and in vivo, using an intracranial xenograft model. Standard techniques for cell culturing, immunohistochemistry, Western blotting, and real-time PCR were employed. The survival of athymic mice (n = 8–10 per group) bearing glioblastoma tumors, treated with CDV alone or in combination with radiation, was analyzed by the Kaplan–Meier method and evaluated with a two-sided log-rank test. Results: CDV possesses potent antineoplastic activity against HCMV-infected glioblastoma cells. This activity is associated with the inhibition of HCMV gene expression and with activation of cellular apoptosis. Surprisingly, we also determined that CDV induces glioblastoma cell death in the absence of HCMV infection. CDV is incorporated into tumor cell DNA, which promotes double-stranded DNA breaks and induces apoptosis. In the setting of ionizing radiotherapy, the standard of care for glioblastoma in humans, CDV augments radiation-induced DNA damage and, further, promotes tumor cell death. Combination therapy with CDV and radiotherapy significantly extended the survival of mice bearing intracranial glioblastoma tumors. Conclusion: We have identified a novel antiglioma property of the FDA-approved drug CDV, which heightens the cytotoxic effect of radiotherapy, the standard of care therapy for glioblastoma. Clin Cancer Res; 19(23); 6473–83. ©2013 AACR.
Effect of Chlorpromazine on the Behaviour of Chronically Overactive Psychotic Patients
Authors: J. Elkes, C. Elkes
Journal: BMJ (1954)

MEDICAL JOURNAL sodium-retainer to correct quickly any serious depletion of this ion.*If there is excessive water retention cortisone will correct this by allowing the selective excretion of water in excess of sodium (Garrod and Wynn, 1954).Since coma occurs in patients with hypopituitarism who are already receiving thyroid extract and testosterone, it is doubtful whether these hormones are of much value in the acute management of this condition.However, if there is obvious myxoedema, L-thyroxine or thyroid extract should be given as well as cortisone and D.C.A., with full aware- ness that their metabolic effects will be delayed. SumnaryDisturbances of consciousness which varied from hypersomnia, mild confusion, and impaired cerebration to stupor and profound coma were encountered in 17 patients with hypopituitarism.There were many factors which precipitated coma, and these included cerebral surgery, pituitary apoplexy, infections, hypoglycaemia, drugs and anaesthetics, elec- trolyte disturbances, water intoxication, and cerebral anoxia.Except in some of the post-operative cases, severe endocrine failure, especially of the adrenal cortex, seemed to be an essential factor in lowering the threshold of consciousness.Cortisone was more effective than thyroxine or testosterone in the prevention and correc- tion of coma.In obscure cases of coma the possibility of hypo- pituitarism should always be considered.The diagnosis, prevention, and treatment of " hypopituitary coma " are discussed in the light of further experience.We are grateful to many physicians in New Zealand and the United Kingdom who have given us access to their cases; to Mr. Anthony James, neurosurgeon of the Dunedin Hospital; and to Dr. C. L. Cope and Dr. T. Russell Fraser, under whose care some of these patients
Effects of sleep posture on upper airway stability in patients with obstructive sleep apnea.
Authors: A M Neill, S M Angus, D Sajkov, R D McEvoy
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Changes in sleep posture have been shown to improve obstructive sleep apnea (OSA). To investigate the mechanisms by which this occurs we assessed upper airway stability in eight patients with severe OSA in three postures (supine, elevated to 30 degrees, and lateral). We used a specially adapted nasal continuous positive airway pressure (nCPAP) mask to measure upper airway closing pressure (UACP) and upper airway opening pressure (UAOP) during non-REM sleep. Statistical comparisons were made between postures using ANOVA for repeated measures. Elevation resulted in a less collapsible airway compared with both the supine and lateral positions (mean UACP: 30 degrees elevation -4.0 +/- 3.2 compared with supine 0.3 +/- 2.4 cm H2O, p < 0.05 and; lateral -1.1 +/- 2.2 cm H2O, p < 0.05). Supine UACP and lateral UACP were not significantly different. Elevation or lateral positioning produced a 50% reduction in mean UAOP (supine 10.4 +/- 3.5 cm H2O compared with 30 degrees elevation 5.3 +/- 2.1, p < 0.05; and lateral 5.5 +/- 2.1 cm H2O, p < 0.05). We conclude that in severely affected OSA patients upper body elevation, and to a lesser extent lateral positioning, significantly improve upper airway stability during sleep, and may allow therapeutic levels of nCPAP to be substantially reduced.
The Polygraph Test — A Flawed Diagnostic Method
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (1992)

Several highly publicized episodes illustrate our continuing faith as a society in a flawed diagnostic test. In May, Roger Coleman, a convicted murderer who vociferously maintained his innocence, was executed in Virginia after failing a polygraph test conducted on the morning of his execution. The same month, Caspar Weinberger, the former Secretary of Defense, used a polygraph test to support his claim that he never lied to protect former president Ronald Reagan in the Iran—Contra scandal. In June, a federal grand jury indicted Weinberger on felony counts of perjury, obstruction of justice, and making false statements related to the scandal. . . .
Tritiated Digoxin Studies in Thyroid Disease.
Authors: James E. Doherty
Journal: Annals of Internal Medicine (1964)

s1 April 1964Tritiated Digoxin Studies in Thyroid Disease.James E. Doherty, M.D., F.A.C.P., W. H. Perkins, M.D., F.A.C.P.James E. Doherty, M.D., F.A.C.P., W. H. Perkins, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-715_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPatients with hypothyroidism appear to be sensitive to digoxin while patients with hyperthyroidism appear to be somewhat resistant to the effects of the drug. This study was undertaken to compare blood levels and excretion of digoxin of patients with thyroid disease to patients with normal thyroid function.Eleven patients with hyperthyroidism and 7 patients with hypothyroidism, as determined by clinical symptoms, I131 uptake, and PBI, were given 1.0 mg of tritiated digoxin intravenously to detect any difference in serum concentrations and excretion when compared to a group of 13 euthyroid patients with congestive heart failure.Frequent serum specimens, urine, and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Little Rock, Arkansas PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdministration of Tritiated Digoxin with and without a Loading Dose 1 April 1964Volume 60, Issue 4Page: 715-715KeywordsAttentionBloodDrugsExcretionHeart failureHyperthyroidismHypothyroidismThyroidThyroid diseasesUrine ePublished: 1 December 2008 Issue Published: 1 April 1964 PDF downloadLoading ...
Surfactant Protein A (SP-A) Reduces Human Rhinovirus 16 (RV16)-Induced Inflammatory Responses In Bronchial Epithelial Cells and Inhibits Viral Replication In H1-HeLa Cells
Authors: Sasipa Tanyaratsrisakul, Ying Wang, Monica Kraft, Mari Nakamura, Dennis R. Voelker
Journal: Journal of Allergy and Clinical Immunology (2014)
THE SIGNIFICANCE OF THE PLASMA TOCOPHEROL CONCENTRATION AND OF TOCOPHEROL TOLERANCE TESTS IN LIVER DISEASE 1
Authors: Gerald Klatskin, Willard A. Krehl
Journal: Journal of Clinical Investigation (1950)

Important relationships between vitamin E metabolism and the state of the liver have been recognized in experimental animals, and there is evidence to suggest that alterations in tocopherol metabolism may occur in humans with liver disease.Diversion of bile from the intestinal tract by chronic biliary fistula produces the typical muscu- lar dystrophy and testicular atrophy of vitamin E deficiency in dogs maintained on normal diets (1).Presumably these effects are due to faulty absorp- tion of the vitamin, since feeding bile results in improvement.Similar observations have been made in the rat (2).Massive necrosis of the liver, produced in rats by diets low in cystine and high in cod liver oil, or containing alkali-treated casein as the sole source of protein, can be prevented by tocopherol ad- ministration (37).The mechanism of this pro- tective action is not known, but it does not appear to be related to the usual vitamin E activity of tocopherol, since the protective dose is many times that required to prevent muscular dystrophy and testicular atrophy (4).Gy6rgy has sug- gested that tocopherol may protect the liver by neutralizing endogenous hepatotoxins which are normally detoxified by methionine and cystine (4).In this connection it is of interest that to- copherol also protects rats against carbon tetra- chloride poisoning (8), and recent work by Hove (9) suggests that the toxic action of carbon tetra- chloride on the liver and other tissues may be due to an induced vitamin' E deficiency.Tocopherol may also have a bearing on hepatic function in connection with its recognized influence on pro- tein (10, 11), fat (7, 12, 13), carbohydrate (14) and vitamin A (15, 16) metabolism.
Acute Haemolytic Anaemia in a Case of Infantile Gastro-enteritis Treated with Oxytetracycline
Authors: E. H. Brown, E. H. Bailey
Journal: BMJ (1958)

MEDICAL JOURNAL_ least) from the animal killed into enough rats (six at least), otherwise light infections can easily be missed.In our opinion Ashcroft inoculated too little blood into too few rats; this may be the reason why he isolated so few strains from such a comparatively large sample of animals.Ex- periments of this kind must be designed with a broad sweep on a large scale and may have to be continued for a con- siderable time.
Sterility—A Remediable Cause
Authors: An Old Practitioner
Journal: JAMA (1913)

<h3>To the Editor:</h3> —When in general practice, I was occasionally consulted for the relief of sterility by couples who had been married several years, and in whom there was no apparent physical disability. In searching for the causes, I found a suggestion in an old edition of the work on midwifery by Cazeaux that led me to think that the condition was often maintained by too frequent sexual indulgence. Cazeaux suggested that in women the ovum is usually thrown off at the time of menstruation; but that during an orgasm provoked by sexual congress the ovum might be discharged at other times. I reasoned that in this way the ova were constantly thrown off before reaching maturity, and therefore were incapable of fecundation. I advised that for five or six months all sexual intercourse should be abstained from excepting immediately before and immediately after menstruation. I feel sure that in
Staffing of Healthcare Workers and Patient Mortality: Randomized Trials Needed
Authors: Meeta Prasad Kerlin
Journal: PLoS Medicine (2014)

In a Perspective accompanying a study by Benjamin Bray and colleagues, Meeta Kerlin discusses the evidence that physician and nurse workforces are associated with patient mortality, why clearer guidelines for appropriate workforce size are not available, and the next steps needed to address the knowledge gaps. Please see later in the article for the Editors' Summary.
Exercise can promote coronary collateral development without improving perfusion of ischemic myocardium.
Authors: W A Neill, J M Oxendine
Journal: Circulation (1979)

We studied the effect of exercise training on the coronary collaterals that developed in response to gradual coronary occlusion in dogs. After their proximal left circumflex coronary artery occlusion, 33 dogs were randomly assigned to exercise or sedentary groups. Coronary collateral function was evaluted 5 weeks or 8 weeks later. The exercised dogs developed better epicardial collateral connections to the occluded left circumflex as judged by higher retrograde blood flow from the distal left circumflex and lower pressure drop across the collaterals. No difference in collaterals was apparent angiographically. Microsphere data indicated that exercise dogs were not better protected against tachycardia provoked subendocardial ischenia in the myocardium supplied by the collaterals.
FOOD ALLERGY AS A POSSIBLE FACTOR IN SUBACUTE RECURRENT ARTHRITIS
Authors: WARREN T. VAUGHAN
Journal: Annals of Internal Medicine (1943)

Article1 July 1943FOOD ALLERGY AS A POSSIBLE FACTOR IN SUBACUTE RECURRENT ARTHRITIS(Abstract)WARREN T. VAUGHAN, M.D.WARREN T. VAUGHAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-19-1-122 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn a consecutive series of 1000 adults complaining primarily of allergy (asthma, hay fever, urticaria, migraine and allergic dermatitis and indigestion), 27 had recurrent subacute involvement of various joints. The allergic etiology in these 27 cases was indicated either by the fact that the causative foods were discovered and the attacks prevented by their avoidance, or that, although the etiologic foods were not discovered, the joint manifestations appeared synchronously with other allergic symptoms and were relieved with improvement in the latter.Thirty-two foods were incriminated. Strawberry and tomato, the "hearsay" foods customarily suspected in rheumatism, were relatively unimportant in this... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAetiology and pathogenesis of rheumatoid arthritisRHEUMATISM AND ARTHRITIS REVIEW OF AMERICAN AND ENGLISH LITERATURE OF RECENT YEARS (Ninth Rheumatism Review)* Part IIPHILIP S. HENCH, M.D., F.A.C.P., WALTER BAUER, M.D., F.A.C.P., EDWARD W. BOLAND, M.D., F.A.C.P., DARRELL C. CRAIN, M.D., F.A.C.P., RICHARD H. FREYBERG, M.D., F.A.C.P., WALLACE GRAHAM, M.D., F.R.C.P.(C), W. PAUL HOLBROOK, M.D., F.A.C.P., L. MAXWELL LOCKIE, M.D., F.A.C.P., CURRIER MCEWEN, M.D., F.A.C.P., EDWARD F. ROSENBERG, M.D., F.A.C.P., ROBERT M. STECHER, M.D., F.A.C.P. 1 July 1943Volume 19, Issue 1Page: 122-124KeywordsAllergy and immunologyArthritisAsthmaEtiologyFeversFoodFood allergiesMigraineUrticaria ePublished: 1 December 2008 Issue Published: 1 July 1943 PDF downloadLoading ...
β1 Integrin Inhibitory Antibody Induces Apoptosis of Breast Cancer Cells, Inhibits Growth, and Distinguishes Malignant from Normal Phenotype in Three Dimensional Cultures and <i>In vivo</i>
Authors: Catherine C. Park, Hui Zhang, Maria Pallavicini, Joe W. Gray, Frederick Baehner, Chong J. Park, Mina J. Bissell
Journal: Cancer Research (2006)

Abstract Current therapeutic approaches to cancer are designed to target molecules that contribute to malignant behavior but leave normal tissues intact. β1 integrin is a candidate target well known for mediating cell-extracellular matrix (ECM) interactions that influence diverse cellular functions; its aberrant expression has been implicated in breast cancer progression and resistance to cytotoxic therapy. The addition of β1 integrin inhibitory agents to breast cancer cells at a single-cell stage in a laminin-rich ECM (three-dimensional lrECM) culture was shown to down-modulate β1 integrin signaling, resulting in malignant reversion. To investigate β1 integrin as a therapeutic target, we modified the three-dimensional lrECM protocol to approximate the clinical situation: before treatment, we allowed nonmalignant cells to form organized acinar structures and malignant cells to form tumor-like colonies. We then tested the ability of β1 integrin inhibitory antibody, AIIB2, to inhibit tumor cell growth in several breast cancer cell lines (T4-2, MDA-MB-231, BT474, SKBR3, and MCF-7) and one nonmalignant cell line (S-1). We show that β1 integrin inhibition resulted in a significant loss of cancer cells, associated with a decrease in proliferation and increase in apoptosis, and a global change in the composition of residual colonies. In contrast, nonmalignant cells that formed tissue-like structures remained resistant. Moreover, these cancer cell–specific antiproliferative and proapoptotic effects were confirmed in vivo with no discernible toxicity to animals. Our findings indicate that β1 integrin is a promising therapeutic target, and that the three-dimensional lrECM culture assay can be used to effectively distinguish malignant and normal tissue response to therapy. (Cancer Res 2006; 66(3): 1526-35)