tbuckley/cabot-search huggingface dataset:
TREM-1–expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases
Authors: Mirjam Schenk, Axel Bouchon, Frank Seibold, Christoph Mueller
Journal: Journal of Clinical Investigation (2007)

Triggering receptor expressed on myeloid cells–1 (TREM-1) potently amplifies acute inflammatory responses by enhancing degranulation and secretion of proinflammatory mediators. Here we demonstrate that TREM-1 is also crucially involved in chronic inflammatory bowel diseases (IBD). Myeloid cells of the normal intestine generally lack TREM-1 expression. In experimental mouse models of colitis and in patients with IBD, however, TREM-1 expression in the intestine was upregulated and correlated with disease activity. TREM-1 significantly enhanced the secretion of relevant proinflammatory mediators in intestinal macrophages from IBD patients. Blocking TREM-1 by the administration of an antagonistic peptide substantially attenuated clinical course and histopathological alterations in experimental mouse models of colitis. This effect was also seen when the antagonistic peptide was administered only after the first appearance of clinical signs of colitis. Hence, TREM-1–mediated amplification of inflammation contributes not only to the exacerbation of acute inflammatory disorders but also to the perpetuation of chronic inflammatory disorders. Furthermore, interfering with TREM-1 engagement leads to the simultaneous reduction of production and secretion of a variety of pro-inflammatory mediators such as TNF, IL-6, IL-8 (CXCL8), MCP-1 (CCL2), and IL-1β. Therefore, TREM-1 may also represent an attractive target for the treatment of chronic inflammatory disorders.
Storage Iron Kinetics. VII. A BIOLOGIC MODEL FOR RETICULOENDOTHELIAL IRON TRANSPORT
Authors: Georges Fillet, James D. Cook, Clement A. Finch
Journal: Journal of Clinical Investigation (1974)

The processing of erythrocyte iron by the reticuloendothelial cell has been characterized by kinetic measurements of blood radioactivity made after the intravenous injection of heat-damaged erythrocytes labeled with (59)Fe and of transferrin-bound (55)Fe. The early reticuloendothelial release of iron, a matter of hours, was calculated from the plasma turnover rate of (55)Fe and the plasma reappearance of (59)Fe. Late release was calculated from the ratio of the cumulative incorporation of both tracers into the circulating red cell mass over a period of 2 wk. There was an initial processing period within the reticuloendothelial cell, after which radioiron either rapidly returned to circulation (t(1/2) 34 min) or was transferred to a slowly exchanging pool of storage iron within the reticuloendothelial cell (t(1/2) release to plasma of 7 days). These pathways were of equal magnitude in the normal dog. Reticuloendothelial release of iron was largely independent of the pre-existing plasma iron level or transferrin saturation. Diurnal fluctuations in the plasma iron level were shown to be the result of a variable partitioning of iron between the early and late release phases. Acute inflammation resulted in a prompt and marked increase in the fraction of iron stored (late phase), whereas depletion of iron stores resulted in a marked increase in early release.
Determinants of Prolonged QT Interval and Their Contribution to Sudden Death Risk in Coronary Artery Disease
Authors: Sumeet S. Chugh, Kyndaron Reinier, Tejwant Singh, Audrey Uy-Evanado, Carmen Socoteanu, Dawn Peters, Ronald Mariani, Karen Gunson, Jonathan Jui
Journal: Circulation (2009)

In a recent cohort study, prolongation of the corrected QT interval (QTc) was associated with an independent increased risk of sudden cardiac death (SCD). We evaluated determinants of prolonged QTc and the relationship of prolonged QTc to SCD risk among patients with coronary artery disease in the general population.A case-control design was used. Cases were SCD patients with coronary artery disease among a metropolitan area of 1 000 000 residents (2002 to 2006); controls were area residents with coronary artery disease but no history of SCD. All cases were required to have an ECG suitable for QTc analysis before and unrelated to the occurrence of SCD. A total of 373 cases and 309 controls met criteria for analysis. Mean QTc was significantly longer in cases than in controls (450+/-45 versus 433+/-37 ms; P<0.0001). In a multivariate model, gender, diabetes mellitus, and QTc-prolonging drugs were significant determinants of QTc prolongation in controls. In a logistic regression model predicting SCD, diabetes mellitus (odds ratio, 1.97; 95% confidence interval, 1.32 to 2.96) and use of QTc-prolonging drugs (odds ratio, 2.90; 95% confidence interval, 1.92 to 4.37) were significant predictors of SCD among subjects with normal or borderline QTc. However, abnormally prolonged QTc in the absence of diabetes and QT-prolonging medications was the strongest predictor of SCD (odds ratio, 5.53; 95% confidence interval, 3.20 to 9.57).Diabetes mellitus and QTc-affecting drugs determined QTc prolongation and were predictors of SCD in coronary artery disease. However, idiopathic abnormal QTc prolongation was associated with 5-fold increased odds of SCD. A continued search for novel determinants of QTc prolongation such as genomic factors is likely to enhance risk stratification for SCD in coronary artery disease.
The deleterious effects of propranolol on patients with cirrhosis
Authors: Cumali Efe, Tugrul Purnak, Ersan Ozaslan
Journal: Hepatology (2010)

We read with great interest the report by Serste et al.1 that describes an observational, prospective study of 151 patients with cirrhosis who did or did not receive beta-blocker therapy for prevention of gastrointestinal bleeding. In this study of propranolol therapy, Child-Pugh class C, hyponatremia, and renal impairment were found to be independent variables of mortality in patients with cirrhosis with refractory ascites. As a result, the authors suggest that propranolol should be contraindicated in these patients. Although the authors did not report the cardiac status of the patients, we would like to discuss their findings in this regard, upon the findings of two recent articles.2, 3 Krag et al.2 evaluated 24 patients with cirrhosis with a cardiac index (CI) above or below 1.5 L/minute/m2, and they found that patients with low CI showed significantly poorer survival than those with a higher CI. In addition, hyponatremia and renal impairment, which are independent variables of mortality in the study report by Serste et al., were found to be associated with lower CI.2 Krag et al. stated that a cardio-renal relation in cirrhosis is most likely the result of chronic circulatory stress combined with more acute events, such as bacterial translocation and systemic inflammatory response, which trigger a systemic response. This may lead to progression of a systolic failure with a decrease in CI, starting a vicious circle in which the decreased CI leads to accentuated arterial underfilling, decreased arterial pressure, and renal perfusion, resulting in deterioration of the renal function, which further enhances cardiac and renal deterioration. Recently, Sharma et al.3 investigated the effects of propranolol on normotensive and hypertensive patients with cirrhosis; they showed that CI significantly decreased after propranolol therapy in both groups. Based on these findings, we think that lowering effects of propranolol on CI and consecutively, development of hyponatremia and renal impairment, may explain the possible mechanism of deleterious effects of propranolol on survival in these patients. Finally, the common usage of beta-blockers for the prevention of variceal bleeding may change in the near future, at least in patients with severe cirrhosis, and band ligation and/or therapies that improve CI may be considered as emerging treatment options to improve survival. Cumali Efe M.D.*, Tugrul Purnak M.D. , Ersan Ozaslan M.D. , * Departments of Internal Medicine, Numune Research and Education Hospital, Ankara, Turkey, Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey.
FDG PET Manifestation of Lobular Panniculitis
Authors: Ruoh-Fang Yen, Chia-Tung Shun, Mei-Hsiu Pan, Ya-Chin Tsai, Yen-Wen Wu
Journal: Clinical Nuclear Medicine (2004)

A 64-year-old woman had intermittent fever for more than a month and was hospitalized. Her initial infectious diagnostic evaluations from chest radiograph, echocardiogram, CT scan of the abdomen, blood culture and urine culture, and bone marrow biopsy were negative. Although the patient began to have a rash several days after admission, her attending doctor did not believe the skin changes were related to her fever. Subsequent F-18 FDG PET revealed multiple foci of intense FDG uptake on the subcutaneous surfaces of back, arms, and thighs. The diagnosis of lobular panniculitis, an inflammatory process of the fat lobules of the subcutaneous tissue, was finally confirmed from skin biopsy.
The Shoulder-Pad Sign — A Diagnostic Feature of Amyloid Arthropathy
Authors: Gary A. Katz, James B. Peter, Carl M. Pearson, William S. Adams
Journal: New England Journal of Medicine (1973)

POLYARTICULAR swelling associated with stiffness, decreased range of motion and pain may be seen in a variety of musculoskeletal disorders. The diagnosis usually depends on multiple features of the clinical presentation and laboratory workup.1 , 2 Key physical signs are important in establishing the diagnosis.In the following cases "the shoulder-pad sign" was a diagnostic feature of amyloid arthropathy.Case ReportsCase 1. A 77-year-old woman was admitted to UCLA Medical Center in 1964 because of painful, stiff and swollen shoulders of 5 months' duration. Physical examination revealed a pale woman with massively enlarged shoulders of a rubbery hard consistence. Shoulder motion . . .
Surgery and Supervoltage Therapy in Treatment of Carcinoma of Lung-Reply
Authors: David P. Boyd
Journal: JAMA (1962)

ABSTRACT To the Editor:— In Dr. William L. Caldwell's letter he asks why we feel that when it can be applied, surgery is the best treatment currently available for bronchogenic carcinoma. The reason for this is that in our experience and in the recorded experience of others surgery has resulted in a 5-year-cure rate of from 25% to 35% of resected cases who survive. I do not believe that there is any other method of therapy available that has approached these figures.We, too, were deeply disappointed in the results of radiation therapy and were slow and reluctant to condemn it. Our declining enthusiasm for this mode of therapy is based on this series of patients and as indicated in the text of the article arises from 2 separate considerations. The first of these is that many patients proceeded to die of dissemination of bronchogenic carcinoma while under therapy, although in
Coping with Myocardial Infarction: A Cognitive-Emotional Perspective
Authors: Hermann Faller
Journal: Psychotherapy and Psychosomatics (1990)

The present paper attempts to make a cognitive-emotional reconstruction of the old, as yet unresolved question as to what role anxiety and denial play as response to acute myocardial infarction (MI). Anxiety is understood as the turning of attention to features of threat, and denial as turning attention away from these features. Each direction is supported by mental argumentations, which is to say subjective theories. A number of relationships between emotional coping and somatic symptoms, such as angina pectoris or atypical chest pain, are treated at greater length. The main areas of perceived stress, lay concepts of etiology, and expectations regarding rehabilitation are explored, taking a cognitive-emotional perspective. The results are discussed in the light of the crucial issue of acceptance MI patients have of psychological treatment.
270 PREDICTIVE MODEL OF RESPONSE TO PEGINTERFERON IN CHRONIC HEPATITIS C: IMPACT OF MUTATIONS IN ISDR AND CORE REGION REVEALED BY CLASSIFICATION AND REGRESSION TREE ANALYSIS
Authors: M. Kurosaki, N. Sakamoto, M. Iwasaki, M. Sakamoto, Y. Suzuki, N. Hiramatsu, F. Sugauchi, A. Tamori, N. Izumi
Journal: Journal of Hepatology (2010)
Snail Recruits Ring1B to Mediate Transcriptional Repression and Cell Migration in Pancreatic Cancer Cells
Authors: Jiangzhi Chen, Hong Xu, Xiuqun Zou, Jiamin Wang, Yi Zhu, Hao Chen, Baiyong Shen, Xiaxing Deng, Aiwu Zhou, Y. Eugene Chin, Frank J. Rauscher, Chenghong Peng, Zhaoyuan Hou
Journal: Cancer Research (2014)

Abstract Transcriptional repressor Snail is a master regulator of epithelial–mesenchymal transition (EMT), yet the epigenetic mechanism governing Snail to induce EMT is not well understood. Here, we report that in pancreatic ductal adenocarcinoma (PDAC), elevated levels of the ubiquitin E3 ligase Ring1B and Snail, along with elevated monoubiquitination of H2A at K119 (H2AK119Ub1), are highly correlated with poor survival. Mechanistic investigations identified Ring1B as a Snail-interacting protein and showed that the carboxyl zinc fingers of Snail recruit Ring1B and its paralog Ring1A to repress its target promoters. Simultaneous depletion of Ring1A and Ring1B in pancreatic cancer cells decreased Snail binding to the target chromatin, abolished H2AK119Ub1 modification, and thereby compromised Snail-mediated transcriptional repression and cell migration. We found that Ring1B and the SNAG-associated chromatin modifier EZH2 formed distinct protein complexes with Snail and that EZH2 was required for Snail-Ring1A/B recruitment to the target promoter. Collectively, our results unravel an epigenetic mechanism underlying transcriptional repression by Snail, suggest Ring1A/B as a candidate therapeutic target, and identify H2AK119Ub1 as a potential biomarker for PDAC diagnosis and prognosis. Cancer Res; 74(16); 4353–63. ©2014 AACR.
INCOMPLETE THREE-VESSEL INTRAVASCULAR IMAGING IN THE PROSPECT TRIAL: IMPLICATIONS FOR PRE-EMPTIVE VULNERABLE PLAQUE DETECTION
Authors: Akiko Maehara, Gary S. Mintz, Alexandra J. Lansky, Ecaterina Cristea, Roxana Mehran, George Dangas, Barry Templin, John McPherson, Bernard de Bruyne, Naim Farhat, Bertil Wennerblom, Andrés Iñiguez, Steven Marso, Patrick W. Serruys, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2010)
Realizing the Promise of the Affordable Care Act—January 1, 2014
Authors: John E. McDonough, Eli Y. Adashi
Journal: JAMA (2014)

Along the arduous, confusing, and contentious road to the enactment and implementation of the Affordable Care Act (ACA), no single date stands out as more consequential for the health and well-being of the US public as does January 1, 2014. Barring unforeseen circumstances, this date will stand out as transformational in the annals of US health care reform. On that day, 4 fundamental provisions of the ACA will take effect. First, extension of the “guaranteed issue” provision to all individual health insurance policies inclusive of the elimination of “medical underwriting” in the face of a preexisting condition. Second, implementation of the “individual shared responsibility” provision also known as the “individual mandate.” Third, provision of tax credits and cost-sharing subsidies to middle- and lower-income adults for the purchase of individual health insurance. And fourth, expansion of Medicaid coverage in participating states to include previously ineligible low-income adults. Most Americans, including physicians and other health care professionals, may not appreciate the profound nature of these new realities. This oversight could be attributable to the daily dramas and controversies of the government shutdown, the woes of the HealthCare.gov website, the cancelation of individual health insurance policies, and the establishment of limited physician networks. In this Viewpoint, we assess the significance of the reforms in question and the implications thereof for the US health care system.
Papillary Thyroid Carcinoma with Predominant Spindle Cell Component: Report of Two Rare Cases and Discussion on the Differential Diagnosis with Other Spindled Thyroid Neoplasm
Authors: Stefania Corrado, Salvatore Maria Corsello, Antonio Maiorana, Esther Diana Rossi, Alfredo Pontecorvi, Guido Fadda, Giampaolo Papi
Journal: Endocrine Pathology (2013)
Brain Scanning in Children
Authors: W. B. Lorentz, J. L. Simon, R. S. Benua
Journal: JAMA (1967)

The results of brain scanning in a series of 97 children are reported. Brain scanning would seem to be a safe, accurate diagnostic screening procedure for suspected intracranial neoplasms. The higher frequency of infratentorial neoplasms in children limits its usefulness as a definitive diagnostic procedure. With the exception of space occupying lesions, the value of scanning in nonneoplastic lesions such as brain abscesses or arteriovenous malformations has not been well established.
DIAGNOSIS OF POLIOMYELITIS
Authors: JOHN A. TOOMEY
Journal: JAMA (1941)

To diagnose poliomyelitis it is necessary to know the types of poliomyelitis that have been described. These are noted in table 1.  Rarely is the clinical disease solely abortive, peripheral, meningeal, cortical, facial or hemiplegic. Usually the patient has a combination of types with spinal or bulbar involvement. Thus, a patient may have a bulbospinal or spinal condition with one or more of the following: meningeal irritation, some form of peripheral nerve irritation, a facial involvement, hemiplegic involvement and, in rare instances, a cortical reaction. Uncomplicated disease of the spinal cord is not fatal unless there is Landry's type of spread of the disease or the infection spreads to and involves the cervical area. Incidentally, the mortality rate is highest in the group of cases of bulbar and bulbospinal poliomyelitis.  Poliomyelitis is a disease of the lower motor neurons. In the fully developed case, the deep reflexes are decreased or
VIRULENCE AND MORPHOLOGICAL CHARACTERISTICS OF MAMMALIAN TUBERCLE BACILLI
Authors: Gardner Middlebrook, René J. Dubos, Cynthia Pierce
Journal: The Journal of Experimental Medicine (1947)

Experimental infection of the mouse can be used for the determination of virulence of cultures of mammalian tubercle bacilli. The relative virulence of such cultures for the mouse is approximately the same as for the guinea pig. Cultures of virulent and avirulent variants of mammalian tubercle bacilli grown in the depth of Tween 80-albumin liquid medium, on the surface of solid agar modifications of this medium, and on the surface of a liquid modification of this medium exhibit consistent morphological differences. All virulent cultures tend to form microscopically demonstrable serpentine cords of varying thickness and length consisting of highly acid-fast bacilli oriented in parallel along the long axis of the cord. The formation of cords appears to be an important factor in conditioning the ability of cultures to spread on the surface of liquid and solid media. It can be inhibited by the addition to the medium of the surface-active water-dispersible oleic acid ester, Tween 80. Avirulent variant bacilli grow in a more or less non-oriented fashion. They have never been observed to form cords under any condition of growth and are much less acid-fast than the virulent cultures when grown in Tween-albumin medium. Two strains of mammalian tubercle bacilli which are intermediate in degree of virulence between the fully virulent and the avirulent variants also exhibit intermediate morphological characteristics.
Acute Promyelocytic Leukaemia
Authors: J. M. Goldman
Journal: BMJ (1974)

Acute promyelocytic leukaemia (A.P.L.) is a rare but important type of acute myeloid leukaemia characterized by major bleeding in association with thrombocytopenia, a specific peripheral blood and bone marrow picture, low plasma fibrinogen, and the presence in the serum of fibrin degradation products. These last abnormalities are related to the disseminated intravascular consumption of coagulation factors with secondary fibrinolysis. A.P.L. requires early recognition and urgent treatment. With optimal management up to half of the patients may achieve complete remission of two years or more. Undoubtedly patients with A.P.L. do especially well when treated in special centres and some patients with A.P.L. now die before the nature of their disease is recognized. Increased familiarity with the problem, which has been known for nearly 20 years, should yield great dividends for those few patients who have this disease.
Increasing incidence of tuberculosis in the young and the elderly in Scotland.
Authors: J. S. Duffield, W. H. Adams, M. Anderson, A. G. Leitch
Journal: Thorax (1996)

Since 1987 there has been an arrest in the previously established decline of tuberculosis notifications in Scotland. A study was undertaken to determine whether age contributed to this phenomenon.Notifications of tuberculosis in Scotland were quantified by year and age group for the years 1981-92 from national statistics supplied by the Information and Statistics Division. Population data were obtained from the 1981 and 1991 national censuses.Age group analysis of pulmonary tuberculosis notifications showed that, in the 0-14 age group, incidence (per 10(5) population) decreased from 7.4 in 1981 to 2.6 in 1987, rising by an estimated 12.6% per annum to 3.7 in 1992. In the 65+ age group incidence declined from 30.1 in 1981 to 17.3 in 1988, and rose by an estimated 4.1% per annum to 22.2 in 1992. In the age groups 15-44 and 45-64 a continuous decrease in notification rate was seen over the period of the study.The plateauing of the incidence of tuberculosis in Scotland is associated with significant increases since 1987 of tuberculosis in the young and elderly. Contributions from ethnic minorities and those infected with HIV are negligible. An ageing population over the decade, with the highest tuberculosis rates seen in the older age group, may explain these findings.
Human Heart–Infiltrating T-Cell Clones From Rheumatic Heart Disease Patients Recognize Both Streptococcal and Cardiac Proteins
Authors: L. Guilherme, E. Cunha-Neto, V. Coelho, R. Snitcowsky, P. M. A. Pomerantzeff, R. V. Assis, F. Pedra, J. Neumann, A. Goldberg, M. E. Patarroyo, F. Pileggi, J. Kalil
Journal: Circulation (1995)

Background β-Hemolytic streptococcal infection in developing countries still causes thousands of cases of rheumatic heart disease, demanding surgical valve correction. Antigenic mimicry between self and streptococcal components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility. Although heart streptococcal–M protein cross-reactive antibodies have been demonstrated, heart tissue damage seems to be T lymphocyte–dependent. We studied the infiltrating T lymphocytes in rheumatic heart lesions with the aim of understanding the role of cellular immune response at the site of the lesions. Methods and Results We obtained 107 T-cell clones from surgical fragments of cardiac tissue from four rheumatic heart disease patients. We tested their capacity to recognize streptococcal M protein–derived synthetic peptides and heart proteins. We found eight infiltrating T-cell clones from all four patients that simultaneously recognize streptococcal M and heart proteins. Among the M-protein sequences tested, only synthetic peptides corresponding to regions 1 through 25, 81 through 103, and 163 through 177 were simultaneously recognized with heart protein fractions. Interestingly, regions 81 through 103 and 163 through 177 have been known to bear heart cross-reactive epitopes at the antibody level. Five of these clones are CD4 + , and one is CD8 + . Conclusions The presence of heart–M protein cross-reactive T-cell clones in rheumatic heart lesions suggests their direct involvement in the pathogenesis of this disease. The dissection of protective and pathogenic epitopes of streptococcal M protein is an important step in allowing the development of a safe anti-streptococcal synthetic vaccine.