tbuckley/cabot-search huggingface dataset:
Italy debates end of life decisions
Authors: Fabio Turone
Journal: BMJ (2006)

Calcineurin inhibitors (CNIs), used as immunosuppressants, have revolutionized transplantation medicine with their strong suppressive activity on alloreactive T lymphocytes; however, they may also cause various adverse effects, including an increased risk for infection and nephrotoxicity. Regulatory T (Treg) cells can complement the deleterious side effects of CNIs with their effective Ag-specific suppressive activities. However, several studies have shown that CNIs suppress Treg cell differentiation. Therefore, an understanding of the mechanisms by which CNIs suppress Treg cell differentiation, as well as an approach for promoting the differentiation of Treg cells in the presence of CNIs, has significant clinical value. In this article, we report that the nuclear orphan receptor Nr4a1 plays a pivotal role in Treg cell differentiation in the presence of CNIs. Unlike that of its family members, Nr4a2 and Nr4a3, the expression of Nr4a1 was not suppressed by CNI treatment, thereby mediating Treg cell differentiation in the presence of CNIs. In a mouse allogeneic graft-versus-host disease model, Nr4a1 mediated tolerance by promoting Treg cell differentiation in mice administered cyclosporine A, prolonging the survival of recipients. Furthermore, activation of Nr4a1 via its agonist partially restored Treg cell differentiation, which was suppressed by cyclosporine A treatment. Finally, we found that the rs2701129 single-nucleotide polymorphism, which was shown to downregulate <i>NR4A1</i> expression, showed a trend toward a higher incidence of chronic graft-versus-host disease in patients undergoing hematopoietic stem cell transplantation. Therefore, our study will be of clinical significance because we demonstrated the role of Nr4a1 in Treg cell differentiation in the presence of CNIs.
Enforced expression of MLL-AF4 fusion in cord blood CD34+ cells enhances the hematopoietic repopulating cell function and clonogenic potential but is not sufficient to initiate leukemia
Authors: Rosa Montes, Verónica Ayllón, Ivan Gutierrez-Aranda, Isidro Prat, M. Carmen Hernández-Lamas, Laura Ponce, Silvia Bresolin, Geertruy te Kronnie, Mel Greaves, Clara Bueno, Pablo Menendez
Journal: Blood (2011)
IDIOTYPIC NETWORKS AND THEIR POSSIBLE EXPLOITATION FOR MANIPULATION OF THE IMMUNE RESPONSE
Authors: I.M. Roitt, D.K. Male, Gabriella Guarnotta, L.P. De Carvalho, Anne Cooke, F.C. Hay, P.M. Lydyard, Yasmin Thanavala, J. Ivanyi
Journal: The Lancet (1981)
Immunologic Treatment of Alzheimer's Disease
Authors: J P Blass
Journal: New England Journal of Medicine (1999)

The recent report by Schenk et al.1 raises the hope of a vaccine for Alzheimer's disease. This report has justifiably received wide attention in both the scientific and lay media. It describes an initial study in transgenic mice, which had been developed as an animal model to test potential treatments for Alzheimer's disease.Scientifically, the paper is straightforward and impressive. The authors studied transgenic mice that overexpress a mutant form of the human amyloid precursor protein. The cerebral amyloidosis that develops in these animals is similar to that in the brains of patients with Alzheimer's disease.1 Cerebral amyloidosis was largely . . .
Chromosomal Abnormalities and Congenital Heart Disease
Authors: INGRID EMERIT, J. DE GROUCHY, P. VERNANT, P. CORONE
Journal: Circulation (1967)

In this study the authors attempted to determine the frequency of the classical chromosomal syndromes as a cause of congenital heart disease and sought other cytogenetic abnormalities in patients with congenital heart disease, selected either for the presence of extracardiac abnormalities or the existence of congenital heart disease in other members of the family. Of the 275 patients whose karyotypes were determined, 119 had a known syndrome. A chromosomal aberration, such as trisomy 21, a sex chromosomal aneuploidy, such as XO, XXY, XYY, XXX, or a more complex mosaic was found in 39. Among the other patients of this group, only a patient with Fanconi's anemia showed abnormalities of the karyotype (numerous chromatid and isochromatid breaks). Among 100 other patients with unclassifiable associated malformations, 10 had abnormal karyotypes. The following abnormalities were noted: complex structural rearrangements, minute chromosome fragments, variations in size of the satellites, presence of unusual satellites on chromosome 17, deletion of the short arm of a D-chromosome, lengthening of chromosome 16, and chromosome breaks. The remaining 56 patients were studied for familial congenital heart disease. Two chromosomal abnormalities were detected in this group. If the classical aberrations are included, the frequency of chromosomal abnormalities as a cause of congenital heart disease may be estimated at between 3 and 5%. This figure should be considered in relation to the methods of recruitment which excluded all patients less than 3 years of age.
Polycythemia Vera and Acute Leukemia
Authors: Leo T. Neu, Marc A. Shuman, Elmer B. Brown
Journal: Annals of Internal Medicine (1975)

Letters1 November 1975Polycythemia Vera and Acute LeukemiaLEO T. NEU, M.D., F.A.C.P., MARC A. SHUMAN, M.D., ELMER B. BROWN, M.D.LEO T. NEU, M.D., F.A.C.P.Search for more papers by this author, MARC A. SHUMAN, M.D.Search for more papers by this author, ELMER B. BROWN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-5-672 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe transformation of polycythemia vera into acute leukemia is a well-documented phenomenon and is reported to occur as a terminal complication in approximately 15% of polycythemia vera patients (1, 2). The role of 32P-therapy in the cause of leukemia in this setting is controversial. We have recently treated a patient with polycythemia vera who developed acute myelomonocytic leukemia. Subsequent to remission induction with chemotherapy, she developed polycythemia vera once again before eventually dying of acute leukemia. To our knowledge, this is the first recorded instance of this sequence of events.The patient, a 67-year-old woman, was found to be polycythemic...References1. MODAN B and LILLIENFELD A: Polycythemia vera and leukemia—the role of radiation treatment. A study of 1222 patients. Medicine 44: 305-344, 1965 CrossrefMedlineGoogle Scholar2. LAWRENCE J, WINCHELL H, and DONALD W: Leukemia in polycythemia vera. Relationship to splenic myeloid metaplasia and therapeutic radiation dose. Ann Intern Med 70:763-771, 1969 LinkGoogle Scholar3. PERLIN E, GRANATIR R, and ROCHE J: Remission of leukemia associated with polycythemia vera (letter). JAMA 223:192, 1973 CrossrefMedlineGoogle Scholar4. LEE S and ROSNER F: Treatment of AGL. Arch Intern Med 123: 205-206, 1969 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: LEO T. NEU, M.D., F.A.C.P.; MARC A. SHUMAN, M.D.; ELMER B. BROWN, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThrombotic complications of polycythemia veraPolycythemia vera: myths, mechanisms, and managementConversion of polycythemia vera to refractory anemia with hyperplastic bone marrowPolycythaemia Vera Terminating in Acute Leukaemia A Clinical, Cytogenetic and Morphologic Study in 8 Patients Treated with Alkylating AgentsSpontaneous Acute Leukemia in Polycythemia VeraW. B. LUNDBERG, M.D., L. R. FARBER, M.D., E. C. CADMAN, M.D., R. T. SKEEL, M.D. 1 November 1975Volume 83, Issue 5 Page: 672-673 Keywords Chemotherapy Myelomonocytic leukemia Polycythemia vera ePublished: 1 December 2008 Issue Published: 1 November 1975 PDF downloadLoading ...
Vascular reactivity during the progression of atherosclerotic plaque. A study in Watanabe heritable hyperlipidemic rabbits.
Authors: F D Kolodgie, R Virmani, H E Rice, W J Mergner
Journal: Circulation Research (1990)

The effects of varying degrees of atherosclerotic plaque on vascular responsiveness in aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits and New Zealand White (normal cholesterolemic) rabbits were studied. Ring segments from the aortic arch and thoracic aorta were mounted in organ chambers for isometric tension recording and measurement of endothelium-derived relaxing factor. WHHL rabbits were divided into three groups according to age: group 1, 3-5 months; group 2, 6-9 months; and group 3, 12-14 months. Atherosclerotic changes (expressed as a percent of total surface area) in the aortic arches in groups 1, 2, and 3 were 11 +/- 3% (mild), 28 +/- 6% (moderate), and 54 +/- 8% (severe) respectively; only occasional plaques were present in the thoracic aorta in all groups. Maximal contractions elicited with phenylephrine progressively decreased with increasing degrees of atherosclerotic plaque. Contractions evoked by histamine were augmented in all groups of WHHL rabbits when compared with controls, whereas those to serotonin were augmented only in vessels with mild atherosclerosis. As the severity of the intimal lesions increased, endothelium-dependent relaxations to acetylcholine, ATP, and calcium ionophore A23187 progressively decreased. Endothelium-independent relaxation to nitroglycerin was virtually complete in all segments. However, vessels with severe atherosclerosis were less sensitive to this agent as illustrated by a significant increase in the ED50 value. Scanning electron microscopy revealed a predominant loss of endothelial cells in the central regions of fibrous plaques. Thus, in WHHL rabbits, hypercholesterolemia and atherosclerosis result in an increased responsiveness of vascular smooth muscle to histamine and serotonin. Endothelium-mediated relaxation of vascular smooth muscle is reduced with the progression of atherosclerosis primarily due to a loss of endothelial cells.
Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge
Authors: Elke O. Luger, Verena Fokuhl, Michael Wegmann, Melanie Abram, Kati Tillack, Gernot Achatz, Rudolf A. Manz, Margitta Worm, Andreas Radbruch, Harald Renz
Journal: Journal of Allergy and Clinical Immunology (2009)
A solitary pulmonary nodule due to eosinophilic granuloma
Authors: GP ten Velde, FB Thunnissen, JM van Engelshoven, EF Wouters
Journal: European Respiratory Journal (1994)

A symptomless 42 year old man with a smoking history of 40 pack-years presented with a solitary pulmonary nodule highly suggestive of lung cancer. Wedge resection proved it to be an eosinophilic granuloma. No other localizations of eosinophilic granuloma were found, and none developed during a 3 yr follow-up.
Transient Cerebral Ischemia Due to Arrhythmia
Authors: Paul F. Walter, Sam D. Reid, Nanette Kass Wenger
Journal: Annals of Internal Medicine (1970)

The diagnostic value of a continuous 10-hr tape-recorded electrocardiogram was evaluated in 39 ambulatory patients with symptoms of cerebral ischemia. Twenty-eight had symptoms of diffuse cerebrovascular insufficiency (dizziness, giddiness or syncope); 11 had classic transient cerebral ischemic attacks. No patient had a prior significant arrhythmia or conduction abnormality diagnosed clinically or by standard electrocardiogram. Patients with bradycardia below 40/min, tachycardia over 150/min, or high-grade atrioventricular (AV) block were considered to have arrhythmias capable of producing their symptoms. Ten of the 39 patients had one of the above arrhythmias; in seven of these the arrhythmias correlated with symptoms. Eight of the 10 "positives" occurred in patients with diffuse cerebrovascular insufficiency; 7 of these had supraventricular tachycardia, and 1 had sinus bradycardia. Specific antiarrhythmic therapy gave an excellent result in five patients and fair improvement in three.
The influence of air conditioning, humidity, temperature and other household characteristics on mite allergen concentrations in the northeastern United States
Authors: R. T. Van Strien, U. Gehring, K. Belanger, E. Triche, J. Gent, M. B. Bracken, B. P. Leaderer
Journal: Allergy (2004)

Background: Information about the influence of housing and occupant characteristics on mite allergen concentrations is crucial to determine which methods could be used to decrease exposure of susceptible subjects. Objectives: To identify housing and occupant characteristics that are associated with mite allergen concentrations in house dust collected from living rooms and mattresses. Methods: We collected dust samples from 750 homes in the northeastern US. The influence of various characteristics on concentrations of mite allergens (Der p 1 and Der f 1) was studied using multiple linear regression analysis. Results: Some characteristics, like absence of air conditioners, the presence of mold or mildew, and a lower temperature were consistently associated with higher concentrations of both mite allergens in dust from all sampling locations. However, none of these factors changed Der p 1 or Der f 1 concentrations by more than a factor of 2. People of white ethnic background had roughly two times higher mite allergen concentrations, while family income, family size, and education level only marginally influenced mite allergen concentrations. Conclusions: Various housing characteristics have some influence on mite allergen concentrations, and could possibly be used to decrease exposure of susceptible subjects. However, only a limited percentage of the variation in mite allergen concentrations was explained by these characteristics.
1001-35 Volume-time curves derived by real-time three-dimensional echocardiography can quantify left ventricular diastolic dysfunction in patients with hypertrophic cardiomyopathy
Authors: Hua Yang, Anna Woo, Michal Jamorski, Katie Fedwick, Daniel Monakier, E.Douglas Wigle, Mani Vannan, Harry Rakowski
Journal: Journal of the American College of Cardiology (2004)
Effects of In Vivo Administration of Anti–B7-1/B7-2 Monoclonal Antibodies on Murine Acute Myocarditis Caused by Coxsackievirus B3
Authors: Yoshinori Seko, Naoyuki Takahashi, Miyuki Azuma, Hideo Yagita, Ko Okumura, Yoshio Yazaki
Journal: Circulation Research (1998)

Abstract —In viral myocarditis, we previously reported that antigen-specific T cells infiltrate the heart and play an important role in the pathogenesis of myocardial damage. For antigen-specific T-cell activation to occur, it is necessary for T cells to receive costimulatory signals provided by costimulatory molecules expressed on antigen-presenting cells as well as main signals provided by binding of T-cell receptors to antigens. To investigate the roles of costimulatory molecules B7-1 and B7-2 in the development of acute viral myocarditis, we first analyzed the expression of B7-1/B7-2 in the hearts of mice with acute viral myocarditis induced by coxsackievirus B3 (CVB3). Second, we evaluated the induction of B7-1/B7-2 in cultured cardiac myocytes treated with interferon gamma (IFN-γ). Third, we examined the effects of in vivo administration of anti–B7-1/B7-2 monoclonal antibodies (mAbs) on the development of acute viral myocarditis. We found that CVB3-induced murine acute myocarditis resulted in enhanced expression of B7-1/B7-2 in cardiac myocytes. The expression of B7-1/B7-2 in cardiac myocytes could be induced in vitro by IFN-γ. We found that in vivo anti–B7-1 mAb treatment markedly decreased myocardial inflammation, whereas anti–B7-2 mAb treatment abrogated the protective effect of anti–B7-1. Our findings indicate that distinct roles for B7-1 and B7-2 antigens are involved in the development of acute viral myocarditis and raise the possibility of immunotherapy with anti–B7-1 mAb to prevent T-cell–mediated myocardial damage in viral myocarditis.
Periodic Extinctions of Transposable Elements in Bacterial Lineages: Evidence from Intragenomic Variation in Multiple Genomes
Authors: Andreas Wagner
Journal: Molecular Biology and Evolution (2005)

Most previous work on the evolution of mobile DNA was limited by incomplete sequence information. Whole genome sequences allow us to overcome this limitation. I study the nucleotide diversity of prominent members of five insertion sequence families whose transposition activity is encoded by a single transposase gene. Eighteen among 376 completely sequenced bacterial genomes and plasmids carry between 3 and 20 copies of a given insertion sequence. I show that these copies generally show very low DNA divergence. Specifically, more than 68% of the transposase genes are identical within a genome. The average number of amino acid replacement substitutions at amino acid replacement sites is Ka = 0.013, that at silent sites is Ks = 0.1. This low intragenomic diversity stands in stark contrast to a much higher divergence of the same insertion sequences among distantly related genomes. Gene conversion among protein-coding genes is unlikely to account for this lack of diversity. The relation between transposition frequencies and silent substitution rates suggests that most insertion sequences in a typical genome are evolutionarily young and have been recently acquired. They may undergo periodic extinction in bacterial lineages. By implication, they are detrimental to their host in the long run. This is also suggested by the highly skewed and patchy distribution of insertion sequences among genomes. In sum, one can think of insertion sequences as slow-acting infectious diseases of cell lineages.
A CASE OF VOLKMANN'S PARALYSIS AND CONTRACTURE.
Authors: FRANCES N. BOYNTON
Journal: JAMA (1907)

In view of the recent publication of an article<sup>1</sup>on Volkmann's paralysis and contracture, giving a history of the literature of the subject and a tabulation of cases, it was thought that the following case, which, through the kindness of Dr. E. H. Arnold, I am permitted to report, might prove of interest. <h3>Patient.</h3> —A. L., girl, aged 5½, was brought to Dr. Arnold, March 1, 1901, with the left hand and wrist paralyzed and contracted. <h3>History.</h3> —Family history and personal history up to time of accident, five months previous, were negative. On Nov. 10, 1900, patient fractured left humerus just above elbow joint. The fracture was reduced and the arm splinted and bandaged. It was not especially painful, but the hand soon puffed up, assumed a wax-like pallor and the fingers began to contract. The attending physician brought another in consultation and the bandages were loosened, but not removed
Local IgA production in patients with chronic bronchitis: effect of acute respiratory infection.
Authors: R A Stockley, D Burnett
Journal: Thorax (1980)

The immunoglobulin A and secretory IgA concentrations were studied in the serum and sputum of patients with chronic bronchitis to determine the effect of active chest infection and inflammation upon the estimation of local IgA production. The sputum/serum albumin ratio was higher during chest infection (5.51; SE+/-1.60x10(-2)) than in the non-infected samples (0.75; SE+/-0.14x10(-2);p less than 0.01) suggesting increased transudation as a result of inflammation. There was a similar increase in sputum/serum IgA during infection from 9.47 (SE+/-1.87)x10(-2) to 41.21 (SE+/-6.92)x10(-2)(p less than 0.01). However, the proportion of IgA locally produced when assessed by conventional techniques was unchanged. There was a significant inverse relationship between the estimated local IgA production of the infected samples and the degree of inflammation (r= -0.972;2p less than 0.001) indicating that inflammation was a major determinant of local IgA production. However, the secretory IgA concentrations of the samples were independent of the degree of inflammation. Furthermore, secretory IgA was found in samples that appeared to have failure of local IgA production using the method of Soutar. Clearer information about local IgA production can be obtained by measuring protein components unique to the bronchial secretions rather than applying correction factors to estimate the contribution of serum components, particularly in the presence of inflammation.
Combining Genomic Profiling (70 Gene-Mammaprint) with Nodal Status Allows To Classify Patients with Primary Breast Cancer and Positive Lymph Nodes (1-9) into Very Distinct Prognostic Subgroups That Could Help Tailor Treatment Strategies.
Authors: M. Saghatchian, S. Mook, G. Pruneri, G. Viale, A. Glas, I. Eekhout, S. Delaloge, L. van 't Veer
Journal: Cancer Research (2009)

Abstract OBJECTIVESThe axillary lymph node (LN) status is considered to be one of the most important factors for chemotherapy decision-making of operable breast cancer patients (pts). It is commonly agreed that combination therapies with taxane-containing regimens should be recommended for these pts, whereas high-dose regimens have failed to provide further improvement for pts clinically considered at high-risk.It has previously been shown that the 70-gene profile (MammaPrint®TM), which was developed in node-negative patients is excellent in predicting disease outcome in pts with 1-3 positive nodes and similarly in pts with 4-9 positive-nodes. Further analysis based on adjuvant treatment received and pooled analysis of the 2 LN positive series was performed in order to assess the prognostic added-value of genomic profiling in LN positive pts.METHODS Frozen tumor samples from breast cancer pts with positive LN coming from 2 hospitals were selected in consecutive series (1-3 LN, 4-9 LN; all female, diagnosed between 1984 and 1995, primary invasive breast carcinoma, unilateral T1, T2 or operable T3, mastectomy or breast-conserving therapy, no prior malignancies, fresh frozen tumor material available). Samples were evaluated by gene expression profiling for the 70-gene profile and were classified as genomic high risk (poor prognosis) or genomic low risk (good prognosis).RESULTS A total of 519 pts have been analyzed: 346 with 1-3 positive LN (PN1) and 173 with 4-9 positive LN (PN2). Among them, 212 (41%) had the 70-gene good prognosis-profile and 307 (59%) had the 70-gene poor prognosis-profile (strictly equal proportions among the 2 LN groups). Median follow-up was 10.3 years: distant metastases occurred in 141 patients (116 as first event) and 103 (20 %) died of their disease. Distance metastases as first event and breast cancer specific survival according to LN group (PN) and genomic profile (MP) are shown in Figures 1 and 2.CONCLUSION Our data show that the 70-gene profile is a strong prognostic marker of distant recurrence and breast specific death in breast cancer patients with positive LN. Combining nodal status (1-3 nodes vs. 4-9 nodes) and 70-gene profile (good vs. poor) allows stratifying patients among subgroups for whom tailored treatment strategies should be designed and assessed based on their very different outcome. Pts with elevated number of lymph nodes and high genomic risk have a very poor prognosis and might need to be considered for stronger treatment strategies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 102.
A SELF-FILLING HYPODERMIC SYRINGE
Authors: A. N. Bessesen
Journal: JAMA (1918)

Local anesthesia is growing in popularity with the medical profession. Generally we have to rely on the ordinary hypodermic syringe for the application of the anesthesia, unless one is fortunate enough to own a Farr apparatus. In the use of the ordinary syringe much time is consumed in refilling, or even in the exchange of syringes. It was with the thought of avoiding this delay that I devised the syringe illustrated. The syringe refills itself from a container attached to the syringe and suspended conveniently from the wrist of the surgeon. In this way a small or large amount of the anesthetic may be injected accurately with the least effort. In the illustration, 7 and 17 indicate the outlet and inlet valves, 11, 15 and 16 the intake channel, and 20 the container for the supply fluid.