tbuckley/cabot-search huggingface dataset:
STUDIES ON ACUTE DISSEMINATED ENCEPHALOMYELITIS PRODUCED EXPERIMENTALLY IN RHESUS MONKEYS. III
Authors: Elvin A. Kabat, Abner Wolf, Ada E. Bezer
Journal: The Journal of Experimental Medicine (1948)

The factor in brain tissue which induces acute disseminated encephalomyelitis, when injected into rhesus monkeys as an emulsion with adjuvants, has been found in human, monkey, rabbit, and chicken brain but is absent from frog and fish brain. It is unaffected by fixation of the brain in formalin, by boiling, and by treatment with ultrasound. It is present in the spinal cord of 3 day old rabbits but does not appear in the rabbit cerebrum until about the 12th day of life; in this respect it parallels the laying down of myelin. Attempts to produce the encephalomyelitis passively with large quantities of serum or of cell exudates, and suspensions of cells from spleen and lymph node from monkeys with encephalomyelitis, were unsuccessful.
Imidazoquinoline Toll-like receptor 8 agonists activate human newborn monocytes and dendritic cells through adenosine-refractory and caspase-1–dependent pathways
Authors: Victoria J. Philbin, David J. Dowling, Leighanne C. Gallington, Guadalupe Cortés, Zhen Tan, Eugénie E. Suter, Kevin W. Chi, Ariel Shuckett, Liat Stoler-Barak, Mark Tomai, Richard L. Miller, Keith Mansfield, Ofer Levy
Journal: Journal of Allergy and Clinical Immunology (2012)
TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis
Authors: Thomas T. Chen, Li Li, Dong-Hui Chung, Christopher D.C. Allen, Suzy V. Torti, Frank M. Torti, Jason G. Cyster, Chih-Ying Chen, Frances M. Brodsky, Eréne C. Niemi, Mary C. Nakamura, William E. Seaman, Michael R. Daws
Journal: The Journal of Experimental Medicine (2005)

T cell immunoglobulin-domain and mucin-domain (TIM) proteins constitute a receptor family that was identified first on kidney and liver cells; recently it was also shown to be expressed on T cells. TIM-1 and -3 receptors denote different subsets of T cells and have distinct regulatory effects on T cell function. Ferritin is a spherical protein complex that is formed by 24 subunits of H- and L-ferritin. Ferritin stores iron atoms intracellularly, but it also circulates. H-ferritin, but not L-ferritin, shows saturable binding to subsets of human T and B cells, and its expression is increased in response to inflammation. We demonstrate that mouse TIM-2 is expressed on all splenic B cells, with increased levels on germinal center B cells. TIM-2 also is expressed in the liver, especially in bile duct epithelial cells, and in renal tubule cells. We further demonstrate that TIM-2 is a receptor for H-ferritin, but not for L-ferritin, and expression of TIM-2 permits the cellular uptake of H-ferritin into endosomes. This is the first identification of a receptor for ferritin and reveals a new role for TIM-2.
EPITHET—where next?
Authors: Peter Sandercock, Joanna Wardlaw, Martin Dennis, Richard Lindley, Graeme Hankey, Karl Matz, Andre Peeters, Stephen Phillips, Gord Gubitz, Kameshwar Prasad, Stefano Ricci, Maria Grazia Celani, Enrico Righetti, Theresa Cantisani, Antonio Arauz, Eivind Berge, Karsten Bruins Slot, Adam Kobayashi, Anna Czlonkowska, Manuel Correia, Veronica Murray, Philippe Lyrer, Graham Venables
Journal: The Lancet Neurology (2008)
Endothelial-to-mesenchymal transition drives atherosclerosis progression
Authors: Pei-Yu Chen, Lingfeng Qin, Nicolas Baeyens, Guangxin Li, Titilayo Afolabi, Madhusudhan Budatha, George Tellides, Martin A. Schwartz, Michael Simons
Journal: Journal of Clinical Investigation (2015)

The molecular mechanisms responsible for the development and progression of atherosclerotic lesions have not been fully established. Here, we investigated the role played by endothelial-to-mesenchymal transition (EndMT) and its key regulator FGF receptor 1 (FGFR1) in atherosclerosis. In cultured human endothelial cells, both inflammatory cytokines and oscillatory shear stress reduced endothelial FGFR1 expression and activated TGF-β signaling. We further explored the link between disrupted FGF endothelial signaling and progression of atherosclerosis by introducing endothelial-specific deletion of FGF receptor substrate 2 α (Frs2a) in atherosclerotic (Apoe(-/-)) mice. When placed on a high-fat diet, these double-knockout mice developed atherosclerosis at a much earlier time point compared with that their Apoe(-/-) counterparts, eventually demonstrating an 84% increase in total plaque burden. Moreover, these animals exhibited extensive development of EndMT, deposition of fibronectin, and increased neointima formation. Additionally, we conducted a molecular and morphometric examination of left main coronary arteries from 43 patients with various levels of coronary disease to assess the clinical relevance of these findings. The extent of coronary atherosclerosis in this patient set strongly correlated with loss of endothelial FGFR1 expression, activation of endothelial TGF-β signaling, and the extent of EndMT. These data demonstrate a link between loss of protective endothelial FGFR signaling, development of EndMT, and progression of atherosclerosis.
<i>HIC2</i> Is a Novel Dosage-Dependent Regulator of Cardiac Development Located Within the Distal 22q11 Deletion Syndrome Region
Authors: Iain M. Dykes, Kelly Lammerts van Bueren, Rebekah J. Ashmore, Thomas Floss, Wolfgang Wurst, Dorota Szumska, Shoumo Bhattacharya, Peter J. Scambler
Journal: Circulation Research (2014)

22q11 deletion syndrome arises from recombination between low-copy repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1 associated with congenital cardiovascular disease. Deletions distal to the typically deleted region result in a similar cardiac phenotype but lack in extracardiac features of the syndrome, suggesting that a second haploinsufficient gene maps to this interval.The transcription factor HIC2 is lost in most distal deletions, as well as in a minority of typical deletions. We used mouse models to test the hypothesis that HIC2 hemizygosity causes congenital heart disease.We created a genetrap mouse allele of Hic2. The genetrap reporter was expressed in the heart throughout the key stages of cardiac morphogenesis. Homozygosity for the genetrap allele was embryonic lethal before embryonic day E10.5, whereas the heterozygous condition exhibited a partially penetrant late lethality. One third of heterozygous embryos had a cardiac phenotype. MRI demonstrated a ventricular septal defect with over-riding aorta. Conditional targeting indicated a requirement for Hic2 within the Nkx2.5+ and Mesp1+ cardiovascular progenitor lineages. Microarray analysis revealed increased expression of Bmp10.Our results demonstrate a novel role for Hic2 in cardiac development. Hic2 is the first gene within the distal 22q11 interval to have a demonstrated haploinsufficient cardiac phenotype in mice. Together our data suggest that HIC2 haploinsufficiency likely contributes to the cardiac defects seen in distal 22q11 deletion syndrome.
Angiogenesis as a target in rheumatoid arthritis
Authors: A E Koch
Journal: Annals of the Rheumatic Diseases (2003)

A ngiogenesis, the growth of new blood vessels, is important in a variety of fibroproliferative disorders, such as diabetic retinopathy, psoriasis, tumour growth, and rheumatoid arthritis (RA). We and others have reviewed this subject recently.1–15 Blood vessel growth probably contributes to the proliferation of the inflammatory synovial pannus as well as to the ingress of inflammatory leucocytes into the synovial tissue. The process of angiogenesis is a fine tuned balance between angiogenesis induction and inhibition. In this article, I will review some of the current advances in the angiogenesis field, specifically focusing on understanding angiogenesis in RA (table 1).

View this table:

 Table 1  
Some angiogenesis inducers relevant to RA



Among the earliest identified angiogenic factors were the fibroblast growth factors. Folkman and colleagues took advantage of the observation that mast cells, which secrete heparin, were often found in proximity to blood vessels.16 Hence, the ability to bind heparin was used as the first method of isolating angiogenic factors. Recently Yamashita and coworkers found that the synovium of patients with RA and joints from rats with adjuvant induced arthritis (AIA) contained increased amounts of fibroblast growth factor-2 (FGF-2).17 Moreover, a Sendai virus containing the FGF-2 gene resulted in worse arthritis in rat AIA, but had no effect on normal joints. Hence, it seems that FGF-2 is important in worsening the progression of experimental arthritis rather than being important in the initiation stage of disease.

An angiogenic mediator which has attracted much attention recently is VEGF, which is an endothelial selective growth factor.18 VEGF induces vascular permeability as well. In human RA, several groups have described VEGF in the joints and serum of patients.19–28 In the control of VEGF secretion in the RA joint, not only do cytokines like interleukin 1 (IL1) and tumour necrosis factor α (TNFα) induce …
Phase I Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With B-Cell Malignancies
Authors: Robert J. Kreitman, David R. Squires, Maryalice Stetler-Stevenson, Pierre Noel, David J.P. FitzGerald, Wyndham H. Wilson, Ira Pastan
Journal: Journal of Clinical Oncology (2005)

Purpose To conduct a phase I trial of recombinant immunotoxin BL22, an anti-CD22 Fv fragment fused to truncated Pseudomonas exotoxin. Patients and Methods Forty-six pretreated patients with CD22+ non-Hodgkin's lymphoma (NHL; n = 4), chronic lymphocytic leukemia (CLL; n = 11), and hairy cell leukemia (HCL; n = 31) received 265 cycles at 3 to 50 μg/Kg every other day × 3 doses. Results BL22 was active in HCL, with 19 complete remissions (CRs; 61%) and six partial responses (PRs; 19%) in 31 patients. Of 19 CRs, 11 were achieved after one cycle and eight after two to 14 cycles. All 25 responders benefited clinically with one cycle. The CR rate was 86% in patients enrolled at ≥ 40 μg/Kg every other day × 3, and 41% at lower doses (P = .011). The median duration for CR was 36 months (range, 5 to 66 months), and eight patients remain in CR at 45 months (range, 29 to 66 months). Lower but significant activity occurred in CLL. Neutralizing antibodies occurred in 11 (24%) of 46 patients (all HCL). A reversible hemolytic uremic syndrome requiring plasmapheresis was observed in one patient with NHL during cycle 1 and in four patients with HCL during cycle 2 or 3. The maximum-tolerated dose (MTD) evaluated at cycle 1 was 40 μg/Kg IV. QOD × 3. The most common toxicities at 30 to 50 μg/Kg every other day × 3 included hypoalbuminemia, transaminase elevations, fatigue, and edema. Conclusion BL22 was well tolerated and highly effective in HCL, even after one cycle. Phase II testing is underway to define the efficacy with one cycle and to study safety when additional cycles are needed for optimal response.
Psychiatry and the Oldest Old
Authors: Dan G. Blazer
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: This article reviews the assessment and management of psychiatric problems among the oldest old. METHOD: The author reviewed the English-language literature pertinent to the characteristics of people 85 years old or older and the assessment and management of psychiatric disorders in this age group with a special focus on depression in the oldest old. RESULTS: Much of the current literature in geriatric psychiatry ignores the oldest old, focusing instead on the treatment of specific psychiatric disorders with unimodal or bimodal therapies. In contrast, geriatric medicine has focused on geriatric syndromes, functional status, comprehensive geriatric assessment, and multimodal intervention. The author describes an approach to treating the oldest old that incorporates depression as an example. This approach is based on the philosophy that has worked well in geriatric medicine but has been increasingly abandoned by psychiatry over recent years. CONCLUSIONS: Comprehensive, interdisciplinary assessment and therapy were the cornerstones of geriatric psychiatry 30 years ago. As psychiatry has moved toward a medical model and emphasized pharmacological therapies, it has moved away from the mainstream of geriatric practice. The time has come for geriatric psychiatry to rejoin geriatric medicine so that psychiatry can recapture its roots and deliver optimal care to the oldest old.
Potential masking effect on dyspnoea perception by short- and long-acting β<sub>2</sub>-agonists in asthma
Authors: C.P. van Schayck, I.D. Bijl-Hofland, S.G.M. Cloosterman, H.T.M. Folgering, F.J.J. van der Elshout, C. Van Weel
Journal: European Respiratory Journal (2002)

Asthma patients evaluate the effect of medication treatment through the degree of their asthma symptoms, which might be affected by their ability to perceive these symptoms. It has been suggested that β 2 -agonists may mask the effects of an increase in airway inflammation. This study compared the perception of histamine-induced bronchoconstriction during monotherapy with short- or long-acting β 2 -agonists. Asthmatic patients (68 male and 60 female, mean age 35±11 yrs, forced expiratory volume in one second (FEV 1 ) 86±15% of the reference value, provocative concentration causing a 20% fall in FEV 1 (PC 20 ) geometric mean 0.97 mg·mL −1 (95% confidence interval (CI): 0.73–1.30)) were selected and randomly allocated to use either a short-acting (salbutamol, n=41) or long-acting β 2 -agonist (formoterol, n=46) or placebo (n=41) for 12 weeks. Perception of dyspnoea provoked by histamine-induced bronchoconstriction was measured at the start and every 4 weeks thereafter. Subjects quantified their sensation of breathlessness during the challenge tests on a modified Borg scale at the start of the study and every 4 weeks thereafter. The sensitivity to changes in FEV 1 was analysed by the linear regression slope (α) Borg versus % fall in FEV 1 . The absolute perceptual magnitude (PS 20 ) was determined by the perception score at the 20% fall in FEV 1 . Although the geometric mean PC 20 decreased significantly within the group using short-acting β 2 -agonists (in the group with initial PC 20 ≥2 mg·mL −1 there was a drop from 5.26–1.94 mg·mL −1 ; p=0.013), repeated measurement analysis showed no difference in the course of time of perception (both slope α and PS 20 ) between the three medication groups. This study showed that chronic use of short- or long-acting β 2 -agonists in asthmatics for a period of 12 weeks, did not significantly change the perception of histamine-induced bronchoconstriction compared with placebo. Further investigation is required to establish whether this suggests that these drugs do not mask a deterioration of asthma.
The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis
Authors: Garcilaso Riesco-Eizaguirre, León Wert-Lamas, Javier Perales-Patón, Ana Sastre-Perona, Lara P. Fernández, Pilar Santisteban
Journal: Cancer Research (2015)

Abstract The presence of differentiated thyroid cells in thyroid cancer is critical for the antitumor response to radioactive iodide treatment, and loss of the differentiated phenotype is a key hallmark of iodide-refractory metastatic disease. The role of microRNAs (miRNA) in fine-tuning gene expression has become a major regulatory mechanism by which developmental and pathologic processes occur. In this study, we performed next-generation sequencing and expression analysis of eight papillary thyroid carcinomas (PTC) to comprehensively characterize miRNAs involved in loss of differentiation. We found that only a small set of abundant miRNAs is differentially expressed between PTC tissue and normal tissue from the same patient. In addition, we integrated computational prediction of potential targets and mRNA sequencing and identified a master miRNA regulatory network involved in essential biologic processes such as thyroid differentiation. Both mature products of mir-146b (miR-146b-5p and -3p) were among the most abundantly expressed miRNAs in tumors. Specifically, we found that miR-146b-3p binds to the 3′-untranslated region of PAX8 and sodium/iodide symporter (NIS), leading to impaired protein translation and a subsequent reduction in iodide uptake. Furthermore, our findings show that miR-146b and PAX8 regulate each other and share common target genes, thus highlighting a novel regulatory circuit that governs the differentiated phenotype of PTC. In conclusion, our study has uncovered the existence of a miR-146b-3p/PAX8/NIS regulatory circuit that may be exploited therapeutically to modulate thyroid cell differentiation and iodide uptake for improved treatment of advanced thyroid cancer. Cancer Res; 75(19); 4119–30. ©2015 AACR.
HYPERTENSION IN PREGNANCY: Current Concepts of Preeclampsia
Authors: Andrea G. Witlin, DO, Baha M. Sibai, MD
Journal: Annual Review of Medicine (1997)

Hypertensive disorders (gestational hypertension, preeclampsia, chronic hypertension, superimposed preeclampsia) are the most common medical complications of pregnancy and constitute a major cause of maternal and perinatal morbidity and mortality. Prediction of those women destined to develop preeclampsia remains elusive. The benefits of calcium supplementation for prevention of preeclampsia are encouraging; however, the definitive study is not yet complete. Aspirin therapy for high-risk has not been helpful; results of therapy for high-risk women are pending. More experience is being gained with antihypertensive therapy and expectant management in severe preeclampsia. Conservative management of severe preeclampsia, when performed in a tertiary care center, may benefit a select group of women and their fetuses.
REMARKS ON THE STATE OF EDUCATION, THE PHYSICAL CAUSES OF DISQUALIFICATION, AND LIABILITY TO DISEASE, OF RECRUITS FROM A MANUFACTURING POPULATION
Authors: J. I. Ikin
Journal: BMJ (1856)

a ane cused by preious peritonitis (a frequent aoueof obstrution of the bowels)and where,Unfortunately, at the after death inspection, all teir anticipations wer but too forcbly verified, as strong cords wer obgerved, which td down the intestine at more than one point.Nothig Will withstand these cords and fibrinous bridles of inflammatory lymph; the spine itself will be bent by them; the thorax, in ome cases of pleurtis, wiU be contracted; while in the peritoneum (only that idiopathic peritonitis, in Dr. Addi- son's experience, is one of the rarest of our diseases) fatal obstruction of the bowels would be most frquent, as super- veamg on these effusions.Dr. Addison, in the majority of oa of obstinate obstruction of the bowels, is an advocate for treating them almost like strangulated hernia.Violent dratic purgatives, fluid mercury, etc, should be used with the utmost circumspection, if not entirely forbidden.In- deed, when such cases are under care in hospital, an oppo-
Epithelioid cell histiocytoma of the skin with clonal<i>ALK</i>gene rearrangement resulting in<i>VCL-ALK</i>and<i>SQSTM1-ALK</i>gene fusions
Authors: J. Jedrych, M. Nikiforova, T.F. Kennedy, J. Ho
Journal: British Journal of Dermatology (2014)

Journal Article Epithelioid cell histiocytoma of the skin with clonal ALK gene rearrangement resulting in VCL–ALK and SQSTM1–ALK gene fusions Get access J. Jedrych, J. Jedrych Department of Dermatology University of Pittsburgh School of Medicine Pittsburgh PA U.S.A Search for other works by this author on: Oxford Academic Google Scholar M. Nikiforova, M. Nikiforova Department of Pathology University of Pittsburgh School of Medicine Pittsburgh PA U.S.A Search for other works by this author on: Oxford Academic Google Scholar T.F. Kennedy, T.F. Kennedy Department of Pathology University of Pittsburgh School of Medicine Pittsburgh PA U.S.A Search for other works by this author on: Oxford Academic Google Scholar J. Ho J. Ho Department of Dermatology University of Pittsburgh School of Medicine Pittsburgh PA U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 5, 1 May 2015, Pages 1427–1429, https://doi.org/10.1111/bjd.13548 Published: 01 May 2015
Life expectancy among HIV-positive patients in Rwanda: a retrospective observational cohort study
Authors: Sabin Nsanzimana, Eric Remera, Steve Kanters, Keith Chan, Jamie I Forrest, Nathan Ford, Jeanine Condo, Agnes Binagwaho, Edward J Mills
Journal: The Lancet Global Health (2015)

BackgroundRwanda has achieved substantial progress in scaling up of antiretroviral therapy. We aimed to assess the effect of increased access to antiretroviral therapy on life expectancy among HIV-positive patients in two distinct periods of lower and higher antiretroviral therapy coverage (1997–2007 and 2008–11).MethodsIn a retrospective observational cohort study, we collected clinical and demographic data for all HIV-positive patients enrolled in care at 110 health facilities across all five provinces of Rwanda. We included patients aged 15 years or older with a known enrolment date between 1997 and 2014. We constructed abridged life tables from age-specific mortality rates and life expectancy stratified by sex, CD4 cell count, and WHO disease stage at enrolment in care and initiation of antiretroviral therapy.FindingsWe included 72 061 patients in this study, contributing 213 983 person-years of follow-up. The crude mortality rate was 33·4 deaths per 1000 person-years (95% CI 32·7–34·2). Life expectancy for the overall cohort was 25·6 additional years (95% CI 25·1–26·1) at 20 years of age and 23·3 additional years (95% CI 22·9–23·7) at 35 years of age. Life expectancy at 20 years of age in the period of 1997–2007 was 20·4 additional years (95% CI 19·5–21·3); for the period of 2008–11, life expectancy had increased to 25·6 additional years (95% CI 24·8–26·4). Individuals enrolling in care with CD4 cell counts of 500 cells per μL or more, and with WHO disease stage I, had the highest life expectancies.InterpretationThis study adds to the growing body of evidence showing the benefit to HIV-positive patients of early enrolment in care and initiation of antiretroviral therapy.FundingBill & Melinda Gates Foundation.
P797 GENETIC ANCESTRY CHARACTERIZATION IN NAFLD PATIENTS FROM BRAZIL AND PORTUGAL
Authors: L.N. Cavalcante, J.T. Stefano, M. Machado, F. Rabelo, D.C. Mazo, A.L.D. Angelo, K. Abe-Sandes, L.G.C. Lyra, F.J. Carrilho, H. Cortez-Pinto, A.C. Lyra, C.P. Oliveira
Journal: Journal of Hepatology (2014)