tbuckley/cabot-search huggingface dataset:
Antagonism of Myostatin Enhances Muscle Regeneration During Sarcopenia
Authors: Victoria Siriett, Mônica Senna Salerno, Carole Berry, Gina Nicholas, Rob Bower, Ravi Kambadur, Mridula Sharma
Journal: Molecular Therapy (2007)

A reduction in muscle mass and strength is often observed with aging, and this phenomenon is known as sarcopenia. This age-related atrophy frequently correlates with insufficient levels of muscle regeneration resulting from impairment of satellite cell involvement and myogenesis brought about by the aged environment. Using myostatin-null mice, we recently showed that negative regulators of muscle mass such as myostatin play an active role in the regulation of myogenesis during aging. The present study specifically tests the therapeutic value of a myostatin antagonist in sarcopenia. We report here that a short-term blockade of myostatin, through stage-specific administration of a myostatin antagonist, significantly enhanced muscle regeneration in aged mice after injury and during sarcopenia. Antagonism of myostatin led to satellite cell activation, increased Pax7 and MyoD protein levels, and greater myoblast and macrophage cell migration, resulting in enhanced muscle regeneration after notexin injury in aged mice. In addition, the antagonist demonstrated a high degree of efficacy, as only minimal doses during the critical period of regeneration after injury were sufficient to restore the myogenic and inflammatory responses in the aged environment. Thus, we propose that the antagonism of myostatin has significant therapeutic potential in the alleviation of sarcopenia.
IMMUNOHISTOCHEMICAL DEMONSTRATION OF THE RETICULOENDOTHELIAL CLEARANCE OF CIRCULATING FIBRIN AGGREGATES
Authors: Leung Lee, Robert T. McCluskey
Journal: The Journal of Experimental Medicine (1962)

In rabbits given an intravenous infusion of thrombin or an injection of endotoxin, immunohistochemical examination of the tissues, using conjugated antiserum against rabbit fibrin, showed bright intracytoplasmic staining in many of the phagocytic cells of the liver and spleen. In normal rabbits as well as in animals injected with large doses of heparin prior to thrombin or endotoxin administration, no such intracellular staining was observed. The findings of this study substantiate the hypothesis that fibrin aggregates formed in the circulating blood during low grade intravascular coagulation are largely removed by the reticuloendothelial system.
Letter: Tuberculosis and renal amyloidosis.
Authors: S N Rizvi, P D Gulati, H Vaishnava
Journal: BMJ (1974)

chlamydial infection, thus making laboratory diagnosis difficult, but will not eradicate the disease.Neomycin is not active against chlamydia, 'but is reasonably effective against bacterial infections and should be the initial antibiotic of choice until swabs can be taken and examined for chlamydia.The persistence of conjunctivitis after neomycin should lead the clinician to investigate the possibility of chlamydial infection in both the infant and its parents.-Weare, etc.,
Preud and the Americans: The Beginnings of Psychoanalysis in the United States, 1876-1917
Authors: Marjorie C. Meehan
Journal: JAMA (1972)

Even those who disagree with Freud's doctrines recognize their profound influence on American thought. But when we talk about the influence of Freud, we are often rather ill informed on the state of psychological and psychiatric opinion prior to the introduction of his teachings. Now this ignorance can be relieved. In this book Hale presents a clear picture of the American climate of opinion, "civilized morality," the "somatic style" of psychiatric thought, the various "mind cures" and mystical trends. Then he tells of the early introduction of some of Freud's ideas, leading to his being invited to lecture at Clark University in 1909. The repercussions of these lectures and the gradual changes in the viewpoints of such men as James Jackson Putnam, William Alanson White, Smith Ely Jelliffe, William James, and Adolph Meyer form a large part of the book, but popular thought and attitudes are also included. This is
Lithium-mediated protection of hippocampal cells involves enhancement of DNA-PK–dependent repair in mice
Authors: Eddy S. Yang, Hong Wang, Guochun Jiang, Somaira Nowsheen, Allie Fu, Dennis E. Hallahan, Fen Xia
Journal: Journal of Clinical Investigation (2009)

Long-term neurological deficiencies resulting from hippocampal cytotoxicity induced by cranial irradiation (IR) present a challenge in the treatment of primary and metastatic brain cancers, especially in children. Previously, we showed that lithium protected hippocampal neurons from IR-induced apoptosis and improved neurocognitive function in treated mice. Here, we demonstrate accelerated repair of IR-induced chromosomal double-strand breaks (DSBs) in lithium-treated neurons. Lithium treatment not only increased IR-induced DNA-dependent protein kinase (DNA-PK) threonine 2609 foci, a surrogate marker for activated nonhomologous end-joining (NHEJ) repair, but also enhanced double-strand DNA end-rejoining activity in hippocampal neurons. The increased NHEJ repair coincided with reduced numbers of IR-induced γ-H2AX foci, well-characterized in situ markers of DSBs. These findings were confirmed in vivo in irradiated mice. Consistent with a role of NHEJ repair in lithium-mediated neuroprotection, attenuation of IR-induced apoptosis of hippocampal neurons by lithium was dramatically abrogated when DNA-PK function was abolished genetically in SCID mice or inhibited biochemically by the DNA-PK inhibitor IC86621. Importantly, none of these findings were evident in glioma cancer cells. These results support our hypothesis that lithium protects hippocampal neurons by promoting the NHEJ repair–mediated DNA repair pathway and warrant future investigation of lithium-mediated neuroprotection during cranial IR, especially in the pediatric population.
THE DIAGNOSIS AND TREATMENT OF ABDOMINAL PAIN.
Authors: JOHN B. DEAVER
Journal: JAMA (1905)

Satisfactorily to elucidate within the limits of an address the subject of the diagnosis and treatment of abdominal pain is a task like that of cleaning the stables of Augeas and would require a second Hercules for its performance. Pain is probably the most constant of all symptoms, no matter what the disease nor where the pathologic lesions are situated, and the abdomen is surgically the most extensive and the most important part of the human body. From the sudden stab of momentary indigestion to the chronic agony of cancerous ulceration, from the burning ache of gastric or intestinal perforations to the prostrating pain of ruptured extrauterine pregnancy, through the whole fell gamut of abdominal disease the surgeon's mind must run, as he seeks here and there a note of hope from the discord of pain, in the effort to snatch his suffering patient from the grave. If at times the opportune moment is lost, if the correct diagnosis is missed, what inexpressible
An Experiment in Education for Family Practice
Authors: Francis S. Caliva
Journal: JAMA (1966)

An experiment in the education of family physicians and in the provision of comprehensive health services to indigent patients is in its third year at St. Joseph's Hospital, a community hospital of 350 beds with a major affiliation with the State University of New York, Upstate Medical Center. The plan, independently designed by interested personnel from the hospital, the local Department of Social Welfare, and the Upstate Medical Center, coincidentally embodies many of the principles recently set forth by Carmichael.<sup>1</sup> It is primarily an attempt to train family physicians in a setting similar to one in which they will ultimately practice, and has been approved by the Council on Medical Education of the American Medical Association as a pilot program in family practice. At the same time, the Family Practice Project (FPP), as it is being called, represents an experimental approach to community health needs by (1) providing an
E-Cadherin Cell-Cell Adhesion in Ewing Tumor Cells Mediates Suppression of Anoikis through Activation of the ErbB4 Tyrosine Kinase
Authors: Hyung-Gyoo Kang, Jasmine M. Jenabi, Jingsong Zhang, Nino Keshelava, Hiroyuki Shimada, William A. May, Tony Ng, C. Patrick Reynolds, Timothy J. Triche, Poul H.B. Sorensen
Journal: Cancer Research (2007)

Abstract Ability to grow under anchorage-independent conditions is one of the major hallmarks of transformed cells. Key to this is the capacity of cells to suppress anoikis, or programmed cell death induced by detachment from the extracellular matrix. To model this phenomenon in vitro, we plated Ewing tumor cells under anchorage-independent conditions by transferring them to dishes coated with agar to prevent attachment to underlying plastic. This resulted in marked up-regulation of E-cadherin and rapid formation of multicellular spheroids in suspension. Addition of calcium chelators, antibodies to E-cadherin (but not to other cadherins or β1-integrin), or expression of dominant negative E-cadherin led to massive apoptosis of spheroid cultures whereas adherent cultures were unaffected. This correlated with reduced activation of the phosphatidylinositol 3-kinase-Akt pathway but not the Ras-extracellular signal–regulated kinase 1/2 cascade. Furthermore, spheroid cultures showed profound chemoresistance to multiple cytotoxic agents compared with adherent cultures, which could be reversed by α-E-cadherin antibodies or dominant negative E-cadherin. In a screen for potential downstream effectors of spheroid cell survival, we detected E-cadherin–dependent activation of the ErbB4 receptor tyrosine kinase but not of other ErbB family members. Reduction of ErbB4 levels by RNA interference blocked Akt activation and spheroid cell survival and restored chemosensitivity to Ewing sarcoma spheroids. Our results indicate that anchorage-independent Ewing sarcoma cells suppress anoikis through a pathway involving E-cadherin cell-cell adhesion, which leads to ErbB4 activation of the phosphatidylinositol 3-kinase-Akt pathway, and that this is associated with increased resistance of cells to cytotoxic agents. [Cancer Res 2007;67(7):3094–105]
Platelet regulatory prostanoids and platelet release products in sickle cell disease
Authors: Gesina L. Longenecker, Barbara J. Beyers, Vipul N. Mankad
Journal: American Journal of Hematology (1992)

Abstract Changes in platelet function have been observed for sickle cell disease (SCO). Levels of the arachidonic acid metabolites, thromboxane A 2 (released by stimulated platelets) and prostacyclin (released from vascular endothelium), which stimulate and inhibit platelets, respectively, have been implicated in overall regulation of platelet function. Circulating basal levels of thromboxane and prostacyclin were determined in 1) a group of SCO volunteers (n = 21; at half‐yearly steady state intervals and also at 24 hr, 72 hr, and 7 days after start of pain crisis) and 2) an age‐, sex‐, and race‐matched control group (n = 18; single determinations). Circulating levels of β‐thromboglobulin (β‐TG), as well as throm‐bin (clotting)‐stimutated platelet release of thromboxane, were also determined. Statistically significant decreases were found for prostacyclin, basal thromboxane, and thrombin‐induced (maximal) thromboxane (alone or per platelet), for steady state SCD vs. normal controls. In addition, significant increases in maximal thromboxane were identified in crises (24, 72 hr) compared with steady state. Crisis β‐TG (24 hr) was significantly elevated compared with controls or steady state SCD. The ratio of basal thromboxane to prostacyclin was increased in crisis, but not significantly. Crisis frequency may correlate in part with changes in platelet function: steady state maximal thromboxane and released thromboxane per platelet were significantly lower in SCD volunteers who had crises during the study vs. those who did not (equivalent study time). The data support altered platelet function in SCD, possibly refractoriness (desensitization), manifest as decreased thromboxane release, to thrombin and/or other stimuli: alternate explanations are discussed. © 1992 Wiley‐Liss, Inc.
Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion.
Authors: D C Parker, D C Wadsworth, G B Schneider
Journal: The Journal of Experimental Medicine (1980)

Cultures of isolated mouse splenic B lymphocytes activated by the divalent F(ab')2 fragment of purified rabbit anti-mouse Fab or class-specific anti-mouse IgM antibodies can be driven on to high rate Ig secretion by the addition of the supernatant fluid of a 24-h culture of concanavalin A-activated spleen cells (SN). The polyclonal antibody response to anti-Ig pus SN is comparable in magnitude with the lipopolysaccharide response as measured in a reverse plaque assay. The addition of SN can be delayed for 24 h after addition of anti-Ig without changing the kinetics of the response. Addition at 48 h delays the response by 24 h. The response to F(ab')2 anti-Fab plus SN is sensitive to Fc-dependent inhibition because intact anti-Fab antibodies inhibit strongly at relatively low concentrations. The monovalent Fab' fragment fails to induce Ig secretion, indicating that cross-linkage of surface immunoglobulin is required. Although the production of active SN is T cell dependent, the response to anti-Ig plus SN is T independent. These findings are interpreted as a polyclonal model of a thymus-dependent antibody response. X
Placebo-controlled trial of vaccination with hepatitis B virus surface antigen in hepatitis B virus transgenic mice
Authors: S.M. Fazle Akbar, Kazunori Kajino, Kenji Tanimoto, Kiyotaka Kurose, Toshikazu Masumoto, Kojiro Michitaka, Norio Horiike, Morikazu Onji
Journal: Journal of Hepatology (1997)
Alzheimer Disease: Current Concepts and Emerging Diagnostic and Therapeutic Strategies
Authors: Thomas E. Finucane
Journal: Annals of Internal Medicine (2004)

Letters6 January 2004Alzheimer Disease: Current Concepts and Emerging Diagnostic and Therapeutic StrategiesThomas E. Finucane, MDThomas E. Finucane, MDFrom Johns Hopkins Bayview Medical Center, Baltimore, MD 21224.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-1-200401060-00031 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Clark and Karlawish misstated an important fact in their Update on Alzheimer disease (1). The practice parameter of the American Academy of Neurology that they referenced in the section on cognitive treatment does not state that “the use of cholinesterase inhibitors constitutes a standard of care for patients with Alzheimer disease.” What the guideline says is, “Cholinesterase inhibitors should be considered in patients with Alzheimer disease (Standard), although studies suggest a small average degree of benefit” (2).References1. Clark CM, Karlawish JH. Alzheimer disease: current concepts and emerging diagnostic and therapeutic strategies. Ann Intern Med. 2003;138:400-10. [PMID: 12614093] LinkGoogle Scholar2. Doody RS, Stevens JC, Beck C, Dubinsky RM, Kaye JA, Gwyther L, et al . Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56:1154-66. [PMID: 11342679] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Johns Hopkins Bayview Medical Center, Baltimore, MD 21224. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAlzheimer Disease: Current Concepts and Emerging Diagnostic and Therapeutic Strategies Christopher M. Clark and Jason H.T. Karlawish Diagnostic Evaluation of Elderly Patients with Mild Memory Problems Jason Karlawish and Christopher M. Clark Metrics Cited ByDementia: Alzheimer's 6 January 2004Volume 140, Issue 1Page: 71KeywordsAlzheimer diseaseCholinesterase inhibitorsNeurologyPatients ePublished: 6 January 2004 Issue Published: 6 January 2004 CopyrightCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
CARRIERS OF LCAT GENE MUTATIONS EXHIBIT INCREASED ATHEROSCLEROSIS: A 3.0 TESLA MRI STUDY
Authors: Raphael Duivenvoorden, Adriaan G. Holleboom, Bas van den Bogaard, Eric de Groot, Aart J. Nederveen, Johan S. Lameris, John JP Kastelein, Jan A. Kuivenhoven, Erik SG Stroes
Journal: Journal of the American College of Cardiology (2010)
Cholesteryl ester accumulation in mouse peritoneal macrophages induced by β-migrating very low density lipoproteins from patients with atypical dysbetalipoproteinemia
Authors: Thomas P. Bersot, Thomas L. Innerarity, Robert W. Mahley, Richard J. Havel
Journal: Journal of Clinical Investigation (1983)

The d < 1.006 lipoproteins of patients in a kindred with atypical dysbetalipoproteinemia induced marked cholesteryl ester accumulation in mouse peritoneal macrophages. The affected family members had severe hypercholesterolemia and hypertriglyceridemia, xanthomatosis, premature vascular disease, the apo-E3/3 phenotype, and a predominance of cholesterol-rich β-very low density lipoproteins (β-VLDL) in the d < 1.006 fraction. When incubated with mouse peritoneal macrophages, the d < 1.006 lipoproteins or β-VLDL from the affected family members stimulated cholesteryl [14C]oleate synthesis 15- to 30-fold above that caused by normal, control d < 1.006 lipoproteins (VLDL). The ability of the β-VLDL to stimulate macrophage cholesteryl ester accumulation was greatly reduced as a consequence of treatment with hypolipidemic agents, which specifically reduced the concentration of β-VLDL. Two important differences were noted in a comparison of the β-VLDL from these atypical dysbetalipoproteinemic subjects with that of classic E2/2 dysbetalipoproteinemics: (a) the β-VLDL from the atypical subjects were severalfold more active in stimulating cholesteryl ester accumulation in macrophages, and (b) both the intestinal and hepatic β-VLDL from the atypical subjects were active. The triglyceriderich, α2-migrating VLDL from the affected family members constituted <10% of the d < 1.006 fraction and were similar to normal VLDL in that they did not stimulate cholesteryl ester synthesis in the macrophages.
Prostate Cancer Screening
Authors: Paul A. Godley
Journal: Annals of Internal Medicine (1994)

Letters15 June 1994Prostate Cancer ScreeningPaul A. Godley, MD, PhD, MPPPaul A. Godley, MD, PhD, MPPUniversity of North Carolina at Chapel Hill; Chapel Hill, NC 27599Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-12-199406150-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I was struck by the contrast presented by the two recent articles on prostate cancer screening. Kramer and colleagues [1] critically evaluated the prostate cancer screening literature, described the biases in nonrandomized studies, estimated the costs of screening, and called for a randomized trial. Walsh [2] strongly advocated prostate cancer screening and aggressive therapy, in part by marshaling data from unpublished presentations, abstracts, and studies found flawed by Kramer and colleagues [1].Although he asserts that symptoms, not screening, cause increased prostate-specific antigen (PSA) use, Walsh grossly overestimated the prevalence of lower urinary tract symptoms at 75% ...References1. Kramer BS, Brown ML, Prorok PC, Potosky AL, Gohagan JK. Prostate cancer screening: what we know and what we need to know. Ann Intern Med. 1993; 119:914-23. Google Scholar2. Walsh PC. Using prostate-specific antigen to diagnose prostate cancer: sailing in uncharted waters (Editorial). Ann Intern Med. 1993; 119:948-9. Google Scholar3. Chute CG, Panser LA, Girman CJ, Oesterling JE, Guess HA, Jacobsen SJ, et al. The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol. 1993; 150:85-9. Google Scholar4. Reynolds T. Prostate cancer rates climbed sharply in 1990 (News). J Natl Cancer Inst. 1993; 85:947-8. Google Scholar5. Stuart ME, Handley MA, Thompson RS, Conger M, Timlin D. Clinical practice and new technology. Prostate-specific antigen (PSA). HMO Practice. 1993; 6:5-11. Google Scholar Author, Article, and Disclosure InformationAuthors: Paul A. Godley, MD, PhD, MPPAffiliations: University of North Carolina at Chapel Hill; Chapel Hill, NC 27599 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 June 1994Volume 120, Issue 12Page: 1052-1053KeywordsAntigensCancer screeningCancer treatmentDigital rectal examinationHealth maintenance organizationsProstate cancerProstate diseasesRadical prostatectomyRandomized trialsSpecificity ePublished: 15 August 2000 Issue Published: 15 June 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Measurement of plasma concentrations of polymorphonuclear elastase-alpha 1 proteinase inhibitor (elastase-alpha 1 antitrypsin) in patients with rheumatoid arthritis: interference by rheumatoid factor.
Authors: R E Banks, S W Evans, K F Taylor, H A Bird, J T Whicher
Journal: Annals of the Rheumatic Diseases (1990)

The plasma concentration of granulocyte elastase in complex with alpha 1 proteinase inhibitor was determined in 32 patients with rheumatoid arthritis and eight with seronegative spondarthritis complicated by peripheral joint synovitis. Most patients had concentrations of complex which were within the range of the control group when measured by an 9in-house9 enzyme linked immunosorbent assay, though several of the patients with rheumatoid arthritis had raised concentrations. When the complexes were measured by a commercially available assay, however, much higher values were obtained for many of the patients with rheumatoid arthritis. Evidence is presented indicating that the commercially available assay may suffer seriously from interference by rheumatoid factor. The possibility is discussed that most patients with rheumatoid arthritis may have plasma concentrations of elastase-alpha 1 PI which are normal or only slightly raised, and that previously published reports using assay systems similar to that available commercially might also have produced falsely raised values for many individuals with rheumatoid arthritis.
The enlargement of small pulmonary arteries by preliminary palliative operations.
Authors: J W Kirklin, L M Bargeron, A D Pacifico
Journal: Circulation (1977)

Four patients with tetralogy of Fallot, three of whom had congenital pulmonary atresia, were treated by initial palliative operations to enlarge left and right pulmonary arteries which were considered too small for complete repair. Two to four years later the right and left pulmonary arteries had enlarged sufficiently to allow complete repair.