tbuckley/cabot-search huggingface dataset:
Selective Tumor Necrosis Factor Receptor I Blockade Is Antiinflammatory and Reveals Immunoregulatory Role of Tumor Necrosis Factor Receptor II in Collagen‐Induced Arthritis
Authors: Fiona E. McCann, Dany P. Perocheau, Gerhard Ruspi, Katrina Blazek, Marie L. Davies, Marc Feldmann, Jonathan L. E. Dean, A. Allart Stoop, Richard O. Williams
Journal: Arthritis & Rheumatology (2014)

Objective Tumor necrosis factor (TNF) signals via 2 receptors, TNFR type I (TNFRI) and TNFRII, with distinct cellular distribution and signaling functions. In rheumatoid arthritis (RA), the net effect of TNFR signaling favors inflammatory responses while inhibiting the activity of regulatory T cells. TNFRII signaling has been shown to promote Treg cell function. To assess the relative contributions of TNFRI and TNFRII signaling to inflammatory and regulatory responses in vivo, we compared the effect of TNF blockade, hence TNFRI/II, versus TNFRI alone in collagen‐induced arthritis (CIA) as a model of RA. Methods Mice with established arthritis were treated for 10 days with anti‐mouse TNFRI domain antibody (dAb; DMS5540), an isotype control dAb (DMS5538), or murine TNFRII genetically fused with mouse IgG1 Fc domain (mTNFRII‐Fc) beginning on the day of arthritis onset, and disease progression was monitored. Systemic cytokine concentrations and numbers of T cell subsets in lymph nodes and spleens were measured, and intrinsic Treg cell function was determined by ex vivo suppression assays. Results Progression of CIA was suppressed similarly by TNFRI (DMS5540) and TNFRI/II (mTNFRII‐Fc) blockade. However, blockade of TNFRI/II led to increased effector T cell activity, which was not observed after selective TNFRI blockade, suggesting an immunoregulatory role of TNFRII. In support of this, TNFRI blockade, but not TNFRI/II blockade, expanded and activated Treg cells. Furthermore, a dramatic increase in expression of the Treg cell signature genes FoxP3 and TNFRII was observed in joints undergoing remission, which supports the notion that these molecules have a physiologic role in the resolution of inflammation. Conclusion We propose that a therapeutic strategy that targets TNFRI while sparing TNFRII has the potential to both inhibit inflammation and promote Treg cell activity, which might be superior to TNF blockade.
Natural History of β-Cell Dysfunction in NIDDM
Authors: John L Leahy
Journal: Diabetes Care (1990)

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and beta-cell dysfunction. This review focuses on the beta-cell, what defects occur when and why. Two major anatomic observations have been made in NIDDM. The beta-cell mass is mildly reduced, especially when obesity is taken into account. Also, amyloid deposits are frequently observed in the islets. It is unclear whether these changes are genetically mediated or result secondary to the loss of glucose homeostasis. Many studies have looked at some aspect of insulin secretion in NIDDM, and two types of distinct abnormalities have been described. Early on, there is a marked disruption in pulsatile insulin delivery, which is potentially an important contributor to the insulin resistance. It is unclear whether the loss of pulsatile delivery is acquired or genetically induced. Later, after glucose intolerance has started, several other secretory abnormalities develop coincident with loss of beta-cell glucorecognition. The net result is further deterioration in timing of insulin delivery and postprandial hyperglycemia. A second important consequence of the glucose blindness is that the inherent compensatory beta-cell mechanisms that guard against hyperglycemia are bypassed. We propose that the loss of glucose responsiveness is a direct result of an elevated glucose concentration (so-called glucotoxicity) and have generated substantial data in rat models that support this idea. The logical conclusion is that beta-cell function in NIDDM can be maximized by achieving the best metabolic control possible.
Safety and Efficacy of Sertraline for Depression in Patients With Heart Failure
Authors: Christopher M. O'Connor, Wei Jiang, Maragatha Kuchibhatla, Susan G. Silva, Michael S. Cuffe, Dwayne D. Callwood, Bosh Zakhary, Wendy Gattis Stough, Rebekka M. Arias, Sarah K. Rivelli, Ranga Krishnan
Journal: Journal of the American College of Cardiology (2010)
Blindness and Visual Impairment in the Republic of Suriname
Authors: Janna Minderhoud, Jerrel C. Pawiroredjo, Herman C.I. Themen, Anne-Marie T. Bueno de Mesquita-Voigt, Michael R. Siban, Cindy M. Forster-Pawiroredjo, Hans Limburg, Ruth M.A. van Nispen, Dennis R.A. Mans, Annette C. Moll
Journal: Ophthalmology (2015)
Multiple pathways are involved in radioprotective effects of lithium chloride in the hippocampal neurons
Authors: Dinesh Kumar Thotala, Eugenia M. Yazlovitskaya, Allie Fu, Dennis E. Hallahan
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4383 

Cranial irradiation therapy used in the treatment of certain cancers often causes neurocognitive deficiency in adult and childhood cancer survivors. This neurocognitive deficit is in part related to decreased neurogenesis and apoptosis of neuronal cells in subgranular zone of the hippocampus. Lithium treatment has been shown to enhance neurogenesis and to have neuroprotective effects in several experimental and clinical settings. Here, we show that lithium treatment decreases radiation-induced apoptosis in the culture of mouse hippocampal neurons HT-22, but not in the glioma cell lines GL261 and D54. The molecular mechanism of this neuroprotective effect of lithium is mediated through multiple pathways. In the present study we demonstrate that Akt/glycogen synthase kinase 3 beta (GSK-3β) is one of the pathways. Τreatment of HT-22 cells with 3 mM LiCl for 7 days results in activation of Akt, followed by inhibition of GSK-3β activity and function of its down-stream targets, β-catenin and cyclin D1. These effects are sustained or facilitated when cells are treated with lithium in combination with ionizing radiation. This combined treatment also alters response of the apoptotic proteins Bcl-2 and Bax to ionizing radiation. The Microarray approach reveals additional set of genes in HT-22 cells, which levels of expression are regulated by lithium. From 38,467 mouse genes studied, several dozen show greater than two-fold increase or reduction in expression following LiCl treatment. Several of the Microarray data are confirmed by real-time PCR and immunoblot analyses. For example, levels of mRNA and protein for decorin, which is known to positively regulate neurogenesis and neuronal response to injury, are increased from 2 to 3-fold. These data show that lithium radioprotective effects are mediated through multiple pathways. Detailed studying of the molecular components of these pathways could uncover additional therapeutic targets for enhanced protection of normal neuronal tissue during radiotherapy.
Abstract 851: Gold nanoparticle-mediated infrared hyperthermia reduces the radiotherapy dose required for tumor therapy
Authors: James F. Hainfeld, Michael J. O'Connor, Lynn Lin, Daniel N. Slatkin, F. Avraham Dilmanian, Henry M. Smilowitz
Journal: Cancer Research (2014)

Abstract Gold nanoparticles (AuNPs) absorb light and can be used to heat and ablate tumors. The “tissue window” at ∼800 nm (near infrared, NIR) is optimal for best tissue penetration (∼2cm). Previously large, 50-150nm gold nanoshells and nanorods that absorb well in the NIR have been used. Here we show that small AuNPs, that may penetrate tumors better, barely absorb at 800nm. However, when conjugated to antitumor antibodies, they are taken up by tumor cells, which catalytically aggregate them by enzyme degradation and pH effects, thus shifting their absorption to the NIR region thereby amplifying their photonic absorption. The AuNPs are NIR transparent until they accumulate in tumor cells; this reduces background heating in blood and non-targeted tissues thereby increasing specificity in contrast to constructs that are always NIR absorbing. We show that treatment of subcutaneous EGFR overexpressing human squamous cell carcinoma (A431) tumor xenografts with 15nm AuNPs conjugated with anti-EGFR and NIR resulted in complete tumor ablation with virtually no normal tissue (skin) damage. Further, using radioresistant mouse squamous cell carcinoma SCCVII xenografts, we have combined AuNP-mediated infrared heating with x-ray therapy to take advantage of the well-known synergy of hyperthermia and radiotherapy. Lipoic Acid modified 15nm AuNPs were injected intratumorally by convection-enhanced delivery (CED) followed by NIR and X-ray therapy. It was found that the dose required for control of 50% the tumors, 55Gy, could be reduced to &amp;lt;15Gy, a factor of 3.7 less. AuNPs therefore provide a method to use hyperthermia to reduce the x-radiation needed for tumor control, thereby sparing normal tissue, reducing side effects and making radiotherapy more effective. Citation Format: James F. Hainfeld, Michael J. O'Connor, Lynn Lin, Daniel N. Slatkin, F. Avraham Dilmanian, Henry M. Smilowitz. Gold nanoparticle-mediated infrared hyperthermia reduces the radiotherapy dose required for tumor therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 851. doi:10.1158/1538-7445.AM2014-851
Effect of cumulative bortezomib dose on survival in multiple myeloma patients receiving bortezomib‐melphalan‐prednisone in the phase III VISTA study
Authors: María Victoria Mateos, Paul G. Richardson, Meletios A. Dimopoulos, Antonio Palumbo, Kenneth C. Anderson, Hongliang Shi, Jennifer Elliott, Edward Dow, Helgi van de Velde, Liviu Niculescu, Jesús F. San Miguel
Journal: American Journal of Hematology (2015)

This analysis, using data from the bortezomib-melphalan-prednisone (VMP) arm of the Phase III VISTA study, investigated whether increased cumulative bortezomib dose could improve overall survival (OS) in transplant-ineligible patients with previously untreated multiple myeloma. Median cumulative bortezomib dose received by the 340 patients was 39 mg/m(2); this was selected as the cut-off for defining the dose groups to be compared for OS. Patient characteristics were well balanced between dose groups except for age. OS was significantly longer in the higher (≥39 mg/m(2)) versus lower (<39 mg/m(2)) cumulative bortezomib dose group (median 66.3 vs. 46.2 months; hazard ratio (HR) 0.533, P < 0.0001; age-adjusted HR 0.561, P = 0.0002). To overcome confounding effects of early discontinuations/deaths, which were more common in the lower cumulative dose group (27 vs. 4% of patients discontinued due to adverse events (AEs) in the lower and higher cumulative dose groups, respectively), a landmark analysis was conducted at 180 days, eliminating patients who died or discontinued before this time from the analysis. OS from this landmark remained significantly longer in the higher dose group (median 60.4 vs. 50.3 months; HR 0.709, P = 0.0372). Thus, higher cumulative bortezomib dose, reflecting prolonged treatment duration and/or dose intensity, appears associated with improved OS. Approaches to achieve higher cumulative doses could include subcutaneous bortezomib administration, dose/schedule modifications, continuing therapy in responding patients, and proactive AE management.
Abstract 18405: Epidrug Treatment Rescues Proliferation and Differentiation in Human Cardiac Mesenchymal Cells of Type 2 Diabetic Patients: A Case of Epimetabolic Memory
Authors: Francesco Spallotta, Chiara Cencioni, Antonella Farsetti, Andreas M Zeiher, Carlo Gaetano
Journal: Circulation (2014)

Introduction: The origin of metabolic/epigenetic memory remains elusive. It, however, may be at the basis of chronic diseases and functional alteration associated to ageing and cardiovascular disease. HYPOTHESIS: Diabetes is known to alter cellular metabolism causing defects in tissue/organ regeneration. In this study we asked whether human cardiac stromal cells from diabetic and normoglycaemic voluntary donors revealed differences associated to their original metabolism and whether the alterations could be rescued by epigenetically active drugs. METHODS and RESULTS: D-CMSC were characterized by a reduced proliferation rate, diminished phosphorylation at histone H3 serine 10 (H3S10P), decreased differentiation potential, and premature cellular senescence. A global histone code profiling of D-CMSC revealed that acetylation on histone H3 lysine 9 (H3K9Ac) and lysine 14 (H3K14Ac) was decreased, whereas the trimethylation of histone H3 lysine 9 and lysine 27 significantly increased. These observations were paralleled by a downregulation of the GCN5- related N-acetyltransferases (GNAT) p300/CBP-associated factor and its isoform 5-a general control of amino acid synthesis (GCN5a), determining a relative decreasein total HAT activity. DNA CpG island hypermethylation was detected at promoters of genes involved in cell growth control and genomic stability. Remarkably, treatment with the GNAT proactivator SPV106 restored normal levels of H3K9Ac and H3K14Ac, reduced DNA CpG hypermethylation, and recovered D-CMSC proliferation and differentiation. CONCLUSIONS: This study investigated the diabetes-associated alterations present in cardiac mesenchymal cells (CMSC) obtained from normoglycemic (ND-CMSC) and type 2 diabetic patients (D-CMSC), identifying the histone acetylase (HAT) activator pentadecylidenemalonate 1b (SPV106) as a potential pharmacological intervention to restore cellular function. These results suggest that epigenetic interventions may reverse alterations in human CMSC obtained from diabetic patients.
Achieving Quality in Cardiovascular Imaging
Authors: Pamela Douglas, Ami E. Iskandrian, Harlan M. Krumholz, Linda Gillam, Robert Hendel, James Jollis, Eric Peterson, Pamela Douglas, Jersey Chen, Linda Gillam, Robert Hendel, James Jollis, Ami E. Iskandrian, Harlan M. Krumholz, Frederick Masoudi, Emile Mohler, Robert L. McNamara, Manesh R. Patel, Eric Peterson, John Spertus
Journal: Journal of the American College of Cardiology (2006)
EXANTHEM SUBITUM; REPORT OF A CASE
Authors: Morgan Cutts
Journal: Annals of Internal Medicine (1938)

Case Reports1 March 1938EXANTHEM SUBITUM; REPORT OF A CASEMORGAN CUTTS, M.D.MORGAN CUTTS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-11-9-1752 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptR. C., a white female aged 31, was first seen on February 3, 1937, complaining of general malaise and weakness of one day's duration. Three days previously she had returned from a week's trip to Texas, and had felt quite well until she noted chilly feelings, weakness, some headache and general malaise on February 2. She had no coryza, sore throat, aching in bones or joints, lacrimation, cough, or pain in the chest, and she had taken no drugs of any kind recently. She had had both measles and rubella as a child, but not scarlet fever, and the remainder...References1. ZAHORSKY J: Roseola infantum, Jr. Am. Med. Assoc., 1913, lxi, 1446. CrossrefGoogle Scholar2. VIEDERHEMPELMANN BSTC: A febrile exanthem occurring in childhood, Jr. Am. Med. Assoc., 1921, lxxvii, 1787. Google Scholar3. ZAHORSKY J in BRENNEMANN: Practice of pediatrics, Vol. ii, chapter 21, 1937, W. F. Prior Co., Hagerstown, Md. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Providence, R. I.*Received for publication July 9, 1937. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byExanthematische InfektionenRoseola Infantum (Exanthem Subitum)ROSEOLA INFANTUMRoseola Infantum (Exanthem Subitum)Exanthem subitum (roseola infantum) 1 March 1938Volume 11, Issue 9Page: 1752-1753KeywordsArthralgiaBoneDrugsEmotionsHeadachesMeaslesPharyngitisRubellaScarlet feverThorax ePublished: 1 December 2008 Issue Published: 1 March 1938 PDF downloadLoading ...
Tort Litigation and Federal Regulation of Medical Devices
Authors: Stephen Piwinski, Shawn Fitzpatrick
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
肠易激综合征的治疗——国内共识意见解读(二)
Authors: 许斌, 袁耀宗
Journal: BMJ (2008)

近年来肠易激综合征（irritable bowel syndrome，IBS）始终是国内外消化疾病领域研究的热点。国内外发表了大量关于IBS基础与临床研究的报告，其治疗药物研发方面也有新的进展。有关功能性胃肠病的罗马Ⅲ诊断标准也在2006年发表，在此基础上2007年由我国相关专家制订了有关IBS诊断和治疗的共识意见（简称长沙共识）。
OBESITY IN DIABETES: A STUDY OF THERAPY WITH ANOREXIGENIC DRUGS
Authors: K E OSSERMAN, H DOLGER
Journal: Annals of Internal Medicine (1951)

ExcerptIn the treatment of the obese diabetic, management of the obesity is secondary to insulin in the control of diabetes mellitus. Mirsky1considers the obese diabetic as being "decompensated" with a relative or absolute insulin insufficiency. With decreased caloric intake and consequent weight reduction, the patient may be restored to "compensation" and the insufficiency of insulin can equal the reduced metabolic demand. If the diabetic patient remains obese, not only may the control of the diabetes become more and more difficult, but reduction in weight eventually may not be effective in restoring carbohydrate tolerance.2The relative insufficiency of insulin then...
Acrylamide-Food Link Questions Linger
Authors: Mike Mitka
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The relationship between left ventricular ejection fraction and mortality in patients with acute heart failure: insights from the <scp>ASCEND‐HF T</scp>rial
Authors: Mustafa Toma, Justin A. Ezekowitz, Jeffrey A. Bakal, Christopher M. O'Connor, Adrian F. Hernandez, Muhammad Rizwan Sardar, Ronald Zolty, Barry M. Massie, Karl Swedberg, Paul W. Armstrong, Randall C. Starling
Journal: European Journal of Heart Failure (2013)
Abstract 819: Type 2 Diabetes Significantly Modulates the Impact of TCF7L2 Variant rs7903146 on the Risk of Coronary Atherosclerosis
Authors: Axel Muendlein, Christoph H Saely, Simone Geller-Rhomberg, Thomas Winder, Alexander Vonbank, Philipp Rein, Heinz Drexel
Journal: Circulation (2009)

Background: Coronary artery disease (CAD) is the most frequent cause of death in type 2 diabetes (T2DM), and CAD shares common risk factors with T2DM. Variations in the transcription factor 7-like ...
Walking in Beauty at Sage Memorial Hospital
Authors: Marsha F Goldsmith
Journal: JAMA (2002)

GANADO, ARIZ—As Sage Memorial Hospital begins its second century of service to people here in the heart of the Navajo Nation, this unique facility located on a compound of 110 acres of high desert in northeastern Arizona faces problems unimagined by the Presbyterian missionaries who founded it in 1901. At the same time, a cadre of dedicated health care professionals, augmented by a frequently changing cast of visiting colleagues, offers the 18000 Navajo people in its service area—1500 sq miles of the 25000-sq mile reservation, the largest in the United States—stateof-the-art attention to their well-being. A short stay in Ganado guided by Louis A. Kazal, Jr, MD, a family physician who spent 10 years here, part of it as the hospital’s medical director, and is now a Robert Wood Johnson Health Policy Fellow in Washington, DC, afforded a glimpse of how a combination of high tech/“high touch” medicine is practiced in a challenging setting. The setting, in Kazal’s words, “is not just rural, it is remote.” Twentyeight miles from Window Rock, Ariz, capital of the Navajo Nation, 176 from Flagstaff, Ariz, and 52 from Gallup, NM, this is country that readers of Tony Hillerman’s mystery novels know well. For others, it is a revelation. Vast stretches of sagebrushcovered earth are dotted with small dwellings, single-story houses or traditional six-sided, east-facing hogans, a daunting distance apart. Outhouses are not unheard of. Sheep and cattle roam on the few paved roads at will, almost as if aware that their economic value to the tribe enhances their safety. Herds of horses graze. Bear and elk live in the nearby Chuska Mountains. An hour’s drive away is Canyon de Chelly, a natural wonder of spectacular beauty and—along with the clean air, the quiet, and the chance to live simply and know one’s neighbors well—one of the big attractions for professional staff, many of whom enjoy hiking and camping. But the bucolic surroundings are no barrier to natural ills. The staff at Sage Memorial, which is a full-time hospital, and its three part-time clinics in the communities of Greasewood (28 miles away), Wide Ruins (20 miles), and Sanders (38 miles), deal with the same medical problems encountered by their city colleagues, as well as those spawned or exacerbated by the situations found on reservations. Few people have much money; many still earn their living by weaving rugs or raising sheep. With a 50% unemployment rate, job opportunities for young people are limited, leading to idle time to indulge in alcohol or other drug use, and frequent domestic abuse. A particular problem is the number of people with diabetes mellitus, nearly all of it type 2. Estimates of its prevalence range widely, but Kazal said he believes nearly one fourth of Navajos are affected.