tbuckley/cabot-search huggingface dataset:
Asymptomatic Aortic Stenosis in the Elderly
Authors: Warren J. Manning
Journal: JAMA (2013)

Aortic stenosis is the most common form of valvular heart disease. Progression of aortic stenosis is very slow and highly variable. Decisions about when to perform valve surgery are made by subjective assessment of patient symptoms and objective measures of the valve and ventricular function by transthoracic echocardiography.To review current concepts regarding the development, progression, and assessment of aortic stenosis; the appropriate monitoring intervals for transthoracic echocardiography; and the indications for valve procedures.Guidelines and literature search.Angina, exertional syncope, and heart failure are key symptoms indicating a need for intervention. The frequency of valvular monitoring by transthoracic echocardiography is guided by the disease severity. Despite evidence of severe disease, valve procedures can safely be deferred if patients experience no symptoms and have normal left ventricular ejection fraction. Asymptomatic patients with severe aortic stenosis may subconsciously curtail their activities to avoid symptoms. Apparently, asymptomatic patients can undergo a carefully monitored exercise stress test to confirm both their asymptomatic status and hemodynamic response to exercise. Bioprosthetic valves are a good replacement alternative for older patients who are good surgical candidates and who have no need for warfarin therapy. For patients who are at high or very high risk of cardiac surgery, transcutaneous aortic valve implantation is an increasing available and preferred over medical management.Asymptomatic patients with severe aortic stenosis require frequent monitoring of their subjective symptoms combined with objective measurement of aortic valve gradient and ventricular function by transthoracic echocardiography. Although conventional surgical replacement remains the mainstay of therapy for aortic stenosis, transcutaneous aortic valve implantation options are evolving.
Collaborative Angiographic Patency Trial of Recombinant Staphylokinase (CAPTORS II)
Authors: Paul W. Armstrong, Jeffrey Burton, Peter G. Molhoek, Amadeo Betriu, Michal Tendera, Christoph Bode, Frits Bar, Jennifer Adgey, Alex Vahanian, Frans Van de Werfs
Journal: Journal of the American College of Cardiology (2002)
Effect of Prenatal Maternal Trait Anxiety on Atopic Dermatitis and Immunoglobulin E Level: Cocoa Study
Authors: Hyun-Ju Cho, Hyoung Yoon Chang, Song-I. Yang, Eun Lee, Dong In Suh, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Eun-jin Kim, Joo-Shil Lee, In Ae Choi, Kyung-Sook Lee, Yee-Jin Shin, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2015)
Prognosis of mucinous histology for patients with radically resected stage II and III colon cancer
Authors: V. Catalano, F. Loupakis, F. Graziano, R. Bisonni, U. Torresi, B. Vincenzi, D. Mari, P. Giordani, P. Alessandroni, L. Salvatore, L. Fornaro, D. Santini, A.M. Baldelli, D. Rossi, L. Giustini, R.R. Silva, A. Falcone, S. D'Emidio, M. Rocchi, S. Luzi Fedeli
Journal: Annals of Oncology (2011)
H-2 restriction of virus-specific T-cell-mediated effector functions in vivo. II. Adoptive transfer of delayed-type hypersensitivity to murine lymphocytic choriomeningits virus is restriced by the K and D region of H-2.
Authors: R M Zinkernagel
Journal: The Journal of Experimental Medicine (1976)

In mice, primary footpad swelling after local infection with lymphocytic choriomeningitis virus (LCMV) and delayed-type hypersensitivity (DTH) adoptively transferred by LCMV immune lymphocytes are T-cell dependent. Nude mice do not develop primary footpad swelling, and T-cell depletion abrogates the capacity to transfer LCMV-specific DTH. Effector T cells involved in eliciting dose-dependent DTH are virus specific in that vaccinia virus-immune lymphocytes could not elicit DTH in LCMV-infected mice. The adoptive transfer of DTH is restricted to H-2K or H-2D compatible donor-recipient combinations. Distinct from the fowl-gamma-globulin DTH model, I-region compatibility is neither necessary nor alone sufficient. Whatever the mechanisms involved in this K- or D-region associated restriction in vivo, it most likely operates at the level of T-cell recognition of "altered self" coded in K or D. T cells associated with the I region (helper T cells and DTH-T cells to fowl-gamma-globulin) are specific for soluble, defined, and inert antigens. T cells associated with the K and D region (T cells cytotoxic in vitro and in vivo for acute LCMV-infected cells, DTH effector T cells, and anti-viral T cells) are specific for infectious, multiplying virus. The fact that T-cell specificity is differentially linked with the I region or with the K and D regions of H-2 may reflect the fundamental biological differences of these antigens. Although it cannot be excluded that separate functional subclasses of T-effector cells could have self-recognizers for different cell surface structures coded in I or K and D, it is more likely that the antigen parameters determine whether T cells are specific for "altered" I or "altered" K- or D-coded structures.
Morning Surge in Blood Pressure as a Predictor of Silent and Clinical Cerebrovascular Disease in Elderly Hypertensives
Authors: Kazuomi Kario, Thomas G. Pickering, Yuji Umeda, Satoshi Hoshide, Yoko Hoshide, Masato Morinari, Mitsunobu Murata, Toshio Kuroda, Joseph E. Schwartz, Kazuyuki Shimada
Journal: Circulation (2003)

Cardiovascular events occur most frequently in the morning hours. We prospectively studied the association between the morning blood pressure (BP) surge and stroke in elderly hypertensives.We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed and silent cerebral infarct was assessed by brain MRI and who were followed up prospectively. The morning BP surge (MS) was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. During an average duration of 41 months (range 1 to 68 months), 44 stroke events occurred. When the patients were divided into 2 groups according to MS, those in the top decile (MS group; MS > or =55 mm Hg, n=53) had a higher baseline prevalence of multiple infarcts (57% versus 33%, P=0.001) and a higher stroke incidence (19% versus 7.3%, P=0.004) during the follow-up period than the others (non-MS group; MS <55 mm Hg, n=466). After they were matched for age and 24-hour BP, the relative risk of the MS group versus the non-MS group remained significant (relative risk=2.7, P=0.04). The MS was associated with stroke events independently of 24-hour BP, nocturnal BP dipping status, and baseline prevalence of silent infarct (P=0.008).In older hypertensives, a higher morning BP surge is associated with stroke risk independently of ambulatory BP, nocturnal BP falls, and silent infarct. Reduction of the MS could thus be a new therapeutic target for preventing target organ damage and subsequent cardiovascular events in hypertensive patients.
Corticosteroid Eye-drops
Authors: G. E. Hewson
Journal: BMJ (1964)

certain peculiar features which suggest that all these remains belong to one family-or to several families united by common -descent."'" Thus three of six crania possess large and uncommon Wormian bones."2Professor Stuart Pigott says this about the bones from Lanhill Long Barrow (Wilts): " It was possible to show that the nine individuals were members of one particular family group, recognizable not only by the striking similarities in features, but also in the presence of the rare Wormian ossicles in seven of the nine skulls."'Anatomists and radiologists, on the other hand, have not been categorical about the alleged familial incidence of Wormian bones.Indeed they appear to have shown little interest in the problem.-Iam, etc.,
A “Spoonful of Sugar” and the Realities of Diabetes Prevention!
Authors: William T. Cefalu
Journal: Diabetes Care (2014)

Given the remarkable progress made to date in regard to unraveling the pathophysiology and natural history of type 2 diabetes, identifying at-risk individuals, and evaluating effective clinical interventions for diabetes prevention, it would be very logical to think that assembling the required resources and implementing the “real-world” translation of findings to prevent type 2 diabetes would be only a matter of time. There is no debate on the need for widespread dissemination of effective interventions to delay onset of type 2 diabetes. First and foremost, there is an incredible amount of data defining the factors contributing to the development of diabetes (e.g., physical inactivity, dietary intake, and obesity). Second, we are all aware of the complications and the financial and emotional costs of the disease. Third, we recognize the global burden of the diabetes epidemic given the prevalence and incidence rates of obesity, prediabetes, and type 2 diabetes reported for each region of the world. And finally, it is no longer questioned that clinical interventions that consist of both lifestyle modification and metformin appear to be effective modalities in reducing the cumulative incidence of diabetes for at least 10 years (1–3). So, is there really any further debate needed regarding this topic? As outlined in this issue of the journal, the answer may not be so clear. Given the importance of this topic, our editorial team has featured articles focused on diabetes prevention in this issue of Diabetes Care —the topics range from discussion of genetic risk and progression to diabetes to policy development (4–8).

In this issue, Sullivan and colleagues, reporting on behalf of the Diabetes Prevention Program (DPP) Research Group, examined the utility of genetic risk scores (GRS) (as developed from a composite of single nucleotide polymorphisms at loci associated with type 2 …
The adaptor molecule CARD9 is essential for tuberculosis control
Authors: Anca Dorhoi, Christiane Desel, Vladimir Yeremeev, Lydia Pradl, Volker Brinkmann, Hans-Joachim Mollenkopf, Karin Hanke, Olaf Gross, Jürgen Ruland, Stefan H.E. Kaufmann
Journal: The Journal of Experimental Medicine (2010)

The cross talk between host and pathogen starts with recognition of bacterial signatures through pattern recognition receptors (PRRs), which mobilize downstream signaling cascades. We investigated the role of the cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) in tuberculosis. This adaptor was critical for full activation of innate immunity by converging signals downstream of multiple PRRs. Card9−/− mice succumbed early after aerosol infection, with higher mycobacterial burden, pyogranulomatous pneumonia, accelerated granulocyte recruitment, and higher abundance of proinflammatory cytokines and granulocyte colony-stimulating factor (G-CSF) in serum and lung. Neutralization of G-CSF and neutrophil depletion significantly prolonged survival, indicating that an exacerbated systemic inflammatory disease triggered lethality of Card9−/− mice. CARD9 deficiency had no apparent effect on T cell responses, but a marked impact on the hematopoietic compartment. Card9−/− granulocytes failed to produce IL-10 after Mycobaterium tuberculosis infection, suggesting that an absent antiinflammatory feedback loop accounted for granulocyte-dominated pathology, uncontrolled bacterial replication, and, ultimately, death of infected Card9−/− mice. Our data provide evidence that deregulated innate responses trigger excessive lung inflammation and demonstrate a pivotal role of CARD9 signaling in autonomous innate host defense against tuberculosis.
Response to Letter Regarding Article, “Ambulatory Blood Pressure Changes After Renal Sympathetic Denervation in Patients With Resistant Hypertension”
Authors: Felix Mahfoud, Christian Ukena, Roland E. Schmieder, Bodo Cremers, Lars C. Rump, Oliver Vonend, Joachim Weil, Martin Schmidt, Uta C. Hoppe, Thomas Zeller, Axel Bauer, Christian Ott, Erwin Blessing, Paul A. Sobotka, Henry Krum, Markus Schlaich, Murray Esler, Michael Böhm
Journal: Circulation (2014)
Endothelin converting enzyme is located on α-actin filaments in smooth muscle cells
Authors: K Barnes
Journal: Cardiovascular Research (1999)

Endothelin converting enzyme is the key enzyme in the generation of endothelin-1 from big-endothelin-1. The mature endothelin-1 is a potent vasoconstrictor which also promotes mitogenesis and proliferation of smooth muscle cells. The objectives were to demonstrate in smooth muscle cells the presence of a phosphoramidon-sensitive endothelin converting enzyme activity, reveal the subcellular localization of the enzyme protein and determine the effects of the metalloproteinase inhibitor, phosphoramidon, the lysosomotrophic drug, chloroquine, and colchicine on the cycling pathway of the enzyme.Subcellular localization of endothelin converting enzyme on human smooth muscle cells and the rat cell line, A7r5, was by immunofluorescence and confocal microscopy or by biotinylation of cell cultures and immunoblotting, after treatment of cell cultures with cytochalasin D, colchicine, chloroquine and phosphoramidon. Converting enzyme activity was determined by high performance liquid chromatographic assay.We detected phosphoramidon-sensitive endothelin converting enzyme activity in smooth muscle cells. In addition to its plasma membrane location, for the first time we revealed a striking co-localization of endothelin converting enzyme and alpha-actin filaments in smooth muscle cells. Colchicine treatment results in a perinuclear accumulation of endothelin converting enzyme. An increased level of endothelin converting enzyme protein was shown to be present in smooth muscle cells which had been grown in the presence of phosphoramidon or chloroquine.The 120 kDa endothelin converting enzyme co-localizes with alpha-actin in smooth muscle cells and resembles that found in endothelial cells in that it is present on both the plasma membrane and intracellularly.
Peripheral Blood Lymphocyte Cell Surface Markers during the Course of Systemic Lupus Erythematosus
Authors: Ronald P. Messner, Folke D. Lindström, Ralph C. Williams
Journal: Journal of Clinical Investigation (1973)

Peripheral blood lymphocytes from 23 patients with active systemic lupus erythematosus (SLE) were serially studied. Changes in bone marrow-derived lymphocytes (B cells), as measured by surface Ig receptors and C3 receptors, and in thymus-derived cells (T cells) measured by rabbit T-cell-specific antiserum and E-binding techniques, were correlated with fluctuations in clinical disease activity and treatment. In normal controls B- and T-cell percentages remained relatively stable, although the situation in SLE was much more labile. A relative and absolute decrease in T lymphocytes and cells bearing a receptor for C3 was found in active lupus. Absolute numbers of cells bearing surface Ig were decreased to a lesser extent, whereas the proportion of these cells was increased. It is postulated that the increase in autoantibody formation and diminished delayed hypersensitivity seen in systemic lupus may be due to a loss of T-lymphocyte function.
THE RENAL LESION ASSOCIATED WITH HEMOGLOBINEMIA
Authors: John R. Jaenike, Eveline E. Schneeberger
Journal: The Journal of Experimental Medicine (1966)

Histological studies have been performed on experimental acute renal failure induced by intravenous injection of hemoglobin in rats. These have been correlated with alterations in renal excretory function, assessed by the measurement of inulin clearance, at various stages of the lesion. The most prominent morphological changes during the first 24 hr after hemoglobin injection, when inulin clearance is most markedly suppressed, are: the presence of hemoglobin within the lumen of small intrarenal vessels, particularly the vasa recta; hemoglobin cast formation involving predominantly the thick ascending limbs of the loops of Henle; and evidence of injury of the epithelium of the proximal tubules and thick ascending limbs. Notably absent during this stage of the lesion are marked tubular dilatation, interstitial edema, and cast formation in the distal collecting ducts. The considerable recovery of function which occurs at 72 hr is accompanied by a marked reduction in involvement of the vasa recta. Standard sections and microdissection reveal many markedly dilated proximal tubules at this stage of the lesion, suggesting obstruction of filtering nephrons. These data have led to a tentative hypothesis regarding the pathogenesis of renal failure in this experimental lesion. It is suggested that renal ischemia and failure of glomerular filtration are the primary factors responsible for the early and severe impairment of renal function, and that these are related to intravascular aggregation of hemoglobin pigment. As this defect recedes, tubular obstruction by hemoglobin casts prevents restitution of excretory function in a variable fraction of the nephrons. The latter accounts for the relatively prolonged, moderate reduction in inulin clearance associated with the late stages of this lesion. These hypotheses form the basis for a continuing study of this renal lesion.
Linkage of Crohn's disease-related serological phenotypes: NFKB1 haplotypes are associated with anti-CBir1 and ASCA, and show reduced NF- B activation
Authors: H Takedatsu, K D Taylor, L Mei, D P B McGovern, C J Landers, R Gonsky, Y Cong, E A Vasiliauskas, A Ippoliti, C O Elson, J I Rotter, S R Targan
Journal: Gut (2008)

Genetics studies of the serum expression of antibodies to microbial antigens may yield important clues to the pathogenesis of Crohn's disease. Our aim was to conduct a linkage study using expression of anti-CBir1, anti-I2, anti-OmpC and ASCA as quantitative traits.Expression of antibodies to microbial antigens was measured by enzyme-linked immunosorbant assay (ELISA) and a standard approximately 10 cM whole genome microsatellite study was conducted. Single nucleotide polymorphism genotyping was performed using either Illumina or TaqMan MGB technology. Nuclear factor Kappa B (NF-kappaB) activation in cells from Epstein-Barr virus (EBV)-transformed cell lines was assessed using an electrophoretic mobility shift assay and protein was measured using ELISA and western blotting.Evidence for linkage to anti-CBir1 expression was detected on human chromosome 4 (logarithm of odds (LOD) 1.82 at 91 cM). We therefore directly proceeded to test the association of haplotypes in NFKB1, a candidate gene. One haplotype, H1, was associated with anti-CBir1 (p = 0.003) and another, H3, was associated with ASCA (p = 0.023). Using cell lines from Crohn's disease patients with either H1 or H3, NF-kappaB activation and NF-kappaB p105 and p50 production were significantly lower for patients with H1 compared to patients with H3.These results suggest that NFKB1 haplotypes induce dysregulation of innate immune responses by altering NF-kappaB expression. The results also show the use of EBV-transformed lymphoblastoid cell lines to conduct phenotypic studies of genetic variation.
Drug-Induced Reduction in Albuminuria Is Associated with Subsequent Renoprotection
Authors: Hiddo J. Lambers Heerspink, Tobias F. Kröpelin, Jarno Hoekman, Dick de Zeeuw
Journal: Journal of the American Society of Nephrology (2014)

Albuminuria has been proposed as a surrogate end point in randomized clinical trials of renal disease progression. Most evidence comes from observational analyses showing that treatment-induced short-term changes in albuminuria correlate with risk change for ESRD. However, such studies are prone to selection bias and residual confounding. To minimize this bias, we performed a meta-analysis of clinical trials to correlate the placebo-corrected drug effect on albuminuria and ESRD to more reliably delineate the association between changes in albuminuria and ESRD. MEDLINE and EMBASE were searched for clinical trials reported between 1950 and April 2014. Included trials had a mean follow-up of ≥1000 patient-years, reported ESRD outcomes, and measured albuminuria at baseline and during follow-up. Twenty-one clinical trials involving 78,342 patients and 4183 ESRD events were included. Median time to first albuminuria measurement was 6 months. Fourteen trials tested the effect of renin-angiotensin-aldosterone-system inhibitors and seven trials tested other interventions. We observed variability across trials in the treatment effect on albuminuria (range, -1.3% to -32.1%) and ESRD (range, -55% to +35% risk change). Meta-regression analysis revealed that the placebo-adjusted treatment effect on albuminuria significantly correlated with the treatment effect on ESRD: for each 30% reduction in albuminuria, the risk of ESRD decreased by 23.7% (95% confidence interval, 11.4% to 34.2%; P=0.001). The association was consistent regardless of drug class (P=0.73) or other patient or trial characteristics. These findings suggest albuminuria may be a valid substitute for ESRD in many circumstances, even taking into account possible other drug-specific effects that may alter renal outcomes.
Vasodilator Therapy in Acute Hemorrhagic Shock
Authors: JAMES A. VICK, HENRY P. CIUCHTA, JOSEPH H. MERICKEL, ESTEN O. LINDSETH
Journal: Circulation Research (1965)

Results of this study show that 18 of 20 dogs survived prolonged periods of arterial hypotension when phenoxybenzamine was given to maintain adequate flow to the vital tissues of the body. This drug was used in order to block the catecholamine-induced arteriolar vasoconstriction and the histamine-induced venospasm. Reduction of peripheral resistance results in an increased perfusion of the capillary beds and a correction of O 2 and CO 2 tensions at the tissue level. One must emphasize the need for adequate fluid replacement, with this form of therapy; otherwise the marked vasodilation which occurs with phenoxybenzamine might result in an inadequate circulation, even as the resistance to flow in hypoxic tissues is eliminated.