tbuckley/cabot-search huggingface dataset:
Renal Excretion of Water, Sodium and Chloride
Authors: ROBERT BIRCHALL, S. W. TUTHILL, W. S. JACOBS, W. J. TRAUTMAN, THOMAS FINDLEY
Journal: Circulation (1953)

There has long been interest in the possibility that a relationship exists between essential hypertension and those endocrine aberrations that involve the hypothalamus, pituitary and adrenal cortex. This paper represents an attempt to study these relationships indirectly by an examination of the manner in which the kidneys of patients with these various diseases handle water, sodium, and chloride.
A Very High Fraction of Unique Intron Positions in the Intron-Rich Diatom Thalassiosira pseudonana Indicates Widespread Intron Gain
Authors: S. W. Roy, D. Penny
Journal: Molecular Biology and Evolution (2007)

Although spliceosomal introns are present in all characterized eukaryotes, intron numbers vary dramatically, from only a handful in the entire genomes of some species to nearly 10 introns per gene on average in vertebrates. For all previously studied intron-rich species, significant fractions of intron positions are shared with other widely diverged eukaryotes, indicating that 1) large numbers of the introns date to much earlier stages of eukaryotic evolution and 2) these lineages have not passed through a very intron-poor stage since early eukaryotic evolution. By the same token, among species that have lost nearly all of their ancestral introns, no species is known to harbor large numbers of more recently gained introns. These observations are consistent with the notion that intron-dense genomes have arisen only once over the course of eukaryotic evolution. Here, we report an exception to this pattern, in the intron-rich diatom Thalassiosira pseudonana. Only 8.1% of studied T. pseudonana intron positions are conserved with any of a variety of divergent eukaryotic species. This implies that T. pseudonana has both 1) lost nearly all of the numerous introns present in the diatom-apicomplexan ancestor and 2) gained a large number of new introns since that time. In addition, that so few apparently inserted T. pseudonana introns match the positions of introns in other species implies that insertion of multiple introns into homologous genic sites in eukaryotic evolution is less common than previously estimated. These results suggest the possibility that intron-rich genomes may have arisen multiple times in evolution. These results also provide evidence that multiple intron insertion into the same site is rare, further supporting the notion that early eukaryotic ancestors were very intron rich.
Importance of Time Spent Standing for Those at Risk of Diabetic Foot Ulceration
Authors: Bijan Najafi, Ryan T. Crews, James S. Wrobel
Journal: Diabetes Care (2010)

OBJECTIVE Despite the high cumulative plantar stress associated with standing, previous physical activity reports of diabetic patients at risk of foot ulceration have not taken this activity into account. This study aimed to monitor spontaneous daily physical activity in diabetic peripheral neuropathy (DPN) patients and examine both walking and standing activities as important foot-loading conditions. RESEARCH DESIGN AND METHODS Thirteen DPN patients were asked to wear a body-worn sensor for 48 h. Body postures (sitting, standing, and lying) and locomotion (walking, number of steps, and postural transition) were extracted. RESULTS Patients daily spent twice as much time standing (13 ± 5%) as walking (6 ± 3%). They spent 37 ± 6% of time sitting and 44 ± 8% lying down. The average number of steps per day was 7,754 ± 4,087, and the number of walking episodes was 357 ± 167 with maximum duration of 3.9 ± 3.8 min. CONCLUSIONS The large portion of DPN patients' time spent standing with the feet loaded requires further consideration when treating and preventing foot ulcers.
Minding the Gap
Authors: Carie S. Facemire, Susan B. Gurley
Journal: Journal of the American Society of Nephrology (2011)

A key component of the kidney's ability to maintain body fluid homeostasis resides in one of its endocrine functions: the production of renin. Control of renin release by renal juxtaglomerular (JG) cells serves to regulate the renin-angiotensin system,[1][1] which is of critical importance for
Lipoxins Attenuate Renal Fibrosis by Inducing let-7c and Suppressing TGFβR1
Authors: Eoin P. Brennan, Karen A. Nolan, Emma Börgeson, Oisín S. Gough, Caitríona M. McEvoy, Neil G. Docherty, Debra F. Higgins, Madeline Murphy, Denise M. Sadlier, Syed Tasadaque Ali-Shah, Patrick J. Guiry, David A. Savage, Alexander P. Maxwell, Finian Martin, Catherine Godson
Journal: Journal of the American Society of Nephrology (2013)

Lipoxins, which are endogenously produced lipid mediators, promote the resolution of inflammation, and may inhibit fibrosis, suggesting a possible role in modulating renal disease. Here, lipoxin A4 (LXA4) attenuated TGF-β1–induced expression of fibronectin, N-cadherin, thrombospondin, and the notch ligand jagged-1 in cultured human proximal tubular epithelial (HK-2) cells through a mechanism involving upregulation of the microRNA let-7c. Conversely, TGF-β1 suppressed expression of let-7c. In cells pretreated with LXA4, upregulation of let-7c persisted despite subsequent stimulation with TGF-β1. In the unilateral ureteral obstruction model of renal fibrosis, let-7c upregulation was induced by administering an LXA4 analog. Bioinformatic analysis suggested that targets of let-7c include several members of the TGF-β1 signaling pathway, including the TGF-β receptor type 1. Consistent with this, LXA4-induced upregulation of let-7c inhibited both the expression of TGF-β receptor type 1 and the response to TGF-β1. Overexpression of let-7c mimicked the antifibrotic effects of LXA4 in renal epithelia; conversely, anti-miR directed against let-7c attenuated the effects of LXA4. Finally, we observed that several let-7c target genes were upregulated in fibrotic human renal biopsies compared with controls. In conclusion, these results suggest that LXA4-mediated upregulation of let-7c suppresses TGF-β1–induced fibrosis and that expression of let-7c targets is dysregulated in human renal fibrosis.
The B lymphocyte stimulator receptor–ligand system in hepatitis C virus-induced B cell clonal disorders
Authors: Dan-Avi Landau, Michelle Rosenzwajg, David Saadoun, David Klatzmann, Patrice Cacoub
Journal: Annals of the Rheumatic Diseases (2008)

Objective: The study aim was to examine the B lymphocyte stimulator (BLyS) receptor–ligand system in hepatitis C virus (HCV)-induced B lymphocyte clonal disorders. Methods: 94 patients with chronic HCV (including 35 with HCV+ mixed cryoglobulinaemia (MC)-vasculitis and nine with HCV+ B cell non-Hodgkin’s lymphoma (B-NHL)) and 15 healthy volunteers were included. Results: A twofold serum BLyS increase was associated with HCV-induced MC-vasculitis, and a threefold increase with HCV-induced B-NHL, compared with patients that were HCV+, but without vasculitis, or healthy controls (p&lt;0.05). Lower membrane BLyS expression in HCV-induced MC-vasculitis was observed. CD19+ BLyS binding and BLyS receptor 3 (BR3) staining showed a stepwise decrease with highest values in healthy controls and who were HCV+ without MC, and lowest in B-NHL (p&lt;0.05, p&lt;0.0001, respectively) with a further decrease in V H 1-69+ clonal B cells. BLyS anti-apoptotic effects were maintained despite this decrease in BR3 staining. Complete clinical remission after antiviral treatment was associated with a decrease in serum BLyS, and an increase in BR3 staining. Rituximab treatment was associated with a fivefold increase in serum BLyS (p&lt;0.001), mirroring the depletion of CD19+ cells. BR3 staining in repopulating B cells was significantly decreased (p&lt;0.005). Conclusions: The BLyS ligand–receptor activity is increased in HCV-induced B cell clonal disorders, indicating a possible role for treatment targeting the BLyS receptor–ligand system.
Audit of respiratory health among brass workers in central Sri Lanka
Authors: Dushantha Madegedara, Damith Nandadeva, Sampath Ranabahu, Samudani Dhanasekara, Hansa Kumara
Journal: European Respiratory Journal (2014)

Background:  Workers who are involved in brass industry are at a higher risk of occupational respiratory diseases as they exposed to heavy metal fumes particularly copper and zinc.   Objective: To study respiratory symptoms, pulmonary function and radiological features in brass workers   Design : Descriptive cross sectional study.   Methods:  brass workers were recruited and screened for respiratory diseases. An individual questionnaire based interview, clinical examination, pulmonary function tests (PFT) and radiological investigations were performed. Results were analyzed using SPSS 16.1statistical software.   Results:  21male workers of 33-77 years (48.05 ± 10.34), who had been in the industry for 180-600 months (260 ± 34.64), were recruited to the study. Respiratory symptoms included wheezing in 5(23.8%), breathlessness in3 (14.2%) and non-specific chest pain in 1(4.7%). Five were found to be smokers. There was no significant difference among symptomatic and asymptomatic subjects regarding the duration of exposure (p=0.431).X-ray abnormalities were detected in 47.6% of the workers which include nodular opacities, peripheral ring shadows and early ground glass appearance. Abnormal PFT were detected in 25%,(20% restrictive 5% mild obstructive ). The duration of exposure significantly correlated with the reduction of forced vital capacity (p=0.011, R= -0.600).55% used improvised face masks. No significant difference was detected in FVC (p=0.267) or FEV1/FVC (p=0.221) with those not using masks.   Conclusion : In this preliminary study it was evident that increasing exposure to metal fumes results in a significant reduction in FVC. Analysis of symptoms is not a good screening tool. The small sample size was a limitation.
An International registry on Autoinflammatory diseases: the Eurofever experience
Authors: Natasa Toplak, Joost Frenkel, Seza Ozen, Helen J Lachmann, Patricia Woo, Isabelle Koné-Paut, Fabrizio De Benedetti, Benedicte Neven, Michael Hofer, Pavla Dolezalova, Jasmin Kümmerle-Deschner, Isabelle Touitou, Veronique Hentgen, Anna Simon, Herman Girschick, Carlos Rose, Carine Wouters, Richard Vesely, Juan Arostegui, Silvia Stojanov, Huri Ozgodan, Alberto Martini, Nicolino Ruperto, Marco Gattorno
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To report on the demographic data from the first 18 months of enrollment to an international registry on autoinflammatory diseases in the context of the Eurofever project. <h3>Methods</h3> A web-based registry collecting baseline and clinical information on autoinflammatory diseases and related conditions is available in the member area of the PRINTO web-site. Anonymised data were collected with standardised forms. <h3>Results</h3> 1880 (M:F=916:964) individuals from 67 centers in 31 countries have been entered in the Eurofever registry. Most of the patients (1388; 74%), reside in western Europe, 294 (16%) in the eastern and southern Mediterranean region (Turkey, Israel, North Africa), 106 (6%) in eastern Europe, 54 in Asia, 27 in South America and 11 in Australia. In total 1049 patients with a clinical diagnosis of a monogenic autoinflammatory diseases have been enrolled; genetic analysis was performed in 993 patients (95%): 703 patients have genetically confirmed disease and 197 patients are heterozygous carriers of mutations in genes that are mutated in patients with recessively inherited autoinflammatory diseases. The median diagnosis delay was 7.3 years (range 0.3–76), with a clear reduction in patients born after the identification of the first gene associated with autoinflammatory diseases in 1997. <h3>Conclusions</h3> A shared online registry for patients with autoinflammatory diseases is available and enrollment is ongoing. Currently, there are data available for analysis on clinical presentation, disease course, and response to treatment, and to perform large scale comparative studies between different conditions.
Effects of Drugs on the Pulmonary Circulation and Ventilation as Reflected by Changes in the Arterial Oxygen Saturation
Authors: ALBERT H. NIDEN, BENJAMIN BURROWS, WILLIAM R. BARCLAY
Journal: Circulation Research (1960)

The effect of: l -epinephrine, acetylcholine, histamine, aminophylline, and serotonin on Ihe pulmonary circulation and ventilation was studied in anesthetized dogs. The following observations were noted: Serotonin produced an increase in arterial oxygen saturation, the other drugs a decrease. Although reduced, the effect was not eliminated by controlling the volume of ventilation or by the inhalation of 25 or 30 percent oxygen. The administration of 100 percent oxygen eliminated the response in all dogs studied. The effect was not abolished by controlling blood flow in addition to ventilation. Changes in the over-all ventilation/perfusion ratio appeared of major importance. In addition, these drugs apparently produced local changes in ventilation/perfusion ratios (physiologic shunting) and/or in the degree of anatomic intrapulmonary shunting of blood. The effects of changes in pulmonary blood flow on peripheral arterial oxygen saturation were also investigated. With the volume of ventilation constant, the following was observed : Increasing pulmonary blood flow by whatever means decreased SaO 2 ; decreasing blood flow resulted in an increase in SaO 2 .
Problems in diagnosing viral hepatitis.
Authors: F Bonino, G Colloredo Mels, G Bellati, G Ideo, F Oliveri, P Colombatto, M R Brunetto
Journal: Gut (1993)

The most reliable method of making a specific aetiological diagnosis of chronic viral hepatitis would be to identify virus specific cytotoxic T lymphocytes responsible for the killing of virus infected hepatocytes in each patient9s liver. Unfortunately, this can not be proposed for routine diagnosis and surrogate tests are required. The detection of virus markers, and even of the virus itself, does not imply that liver damage is caused by virus infection. Indirect markers of the host9s antiviral immunoresponse have to be used to confirm more specifically the diagnosis of viral hepatitis. IgM antibodies against viral antigens implicated in the elimination of the virus seem to be suitable alternative candidates. Significant changes in the serum values of viraemia and aminotransferases occur within a few days, while a significant variation in liver histology takes much longer. Only the kinetics of the highly variable parameters can be used for an appropriate study of the relationship between viraemia, antiviral immunoresponse, and liver cell necrosis. Quantitative and dynamic analyses of hepatitis virus markers seem the most suitable and reliable methods of monitoring the patients eligible for antiviral treatment and identifying the most appropriate time to start this.
ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use
Authors: Deepak L. Bhatt, James Scheiman, Neena S. Abraham, Elliott M. Antman, Francis K.L. Chan, Curt D. Furberg, David A. Johnson, Kenneth W. Mahaffey, Eamonn M. Quigley
Journal: Circulation (2008)
Tumor necrosis factor alpha-induced angiogenesis depends on in situ platelet-activating factor biosynthesis.
Authors: G Montrucchio, E Lupia, E Battaglia, G Passerini, F Bussolino, G Emanuelli, G Camussi
Journal: The Journal of Experimental Medicine (1994)

Tumor necrosis factor (TNF) alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Therefore, it was suggested that the angiogenic properties of this agent might be consequent to the production of secondary mediators. Since TNF-alpha stimulates the synthesis of platelet-activating factor (PAF) by monocytes and endothelial cells, we investigated the possible involvement of PAF in the angiogenic effect of TNF-alpha. Angiogenesis was studied in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model the angiogenesis induced by TNF-alpha was shown to be inhibited by WEB 2170, a specific PAF receptor antagonist. Moreover, in mice injected with TNF-alpha, PAF was detected within the Matrigel, 6 and 24 h after TNF-alpha injection. The synthesis of PAF within the Matrigel was concomitant with the early migration of endothelial cells and infiltration of monocytes. No infiltration of lymphocytes or polymorphonuclear leukocytes was observed. Synthetic PAF as well as PAF extracted and purified from mice challenged with TNF-alpha induced a rapid angiogenic response, inhibited by WEB 2170. These results suggest that the angiogenic effect of TNF-alpha is, at least in part, mediated by PAF synthesized from monocytes and/or endothelial cells infiltrating the Matrigel plug.
New treatments in multiple myeloma: beyond optimal treatment
Authors: J.-L. Harousseau
Journal: Annals of Oncology (2008)

The prognosis of multiple myeloma (MM) has remained unchanged for three decades. The first improvement appeared in the 1990s when the Intergroupe Francophone du Myelome (IFM) 90 randomized trial showed the superiority of high-dose therapy supported by autologous stem cell transplantation (ASCT) compared with conventional dose chemotherapy in younger patients (<65 years of age) [1]. These results were confirmed by two other randomized studies [2–3]. But in less than 10 years, treatment of MM has dramatically changed due to the introduction of three novel agents: thalidomide, its analogue lenalidomide, and bortezomib. Compared with chemotherapeutic agents, these new compounds have different modes of action. They target not only the myeloma cell but also the microenvironment which is so important for myeloma cell survival and proliferation.
Atypical erythema multiforme is a prognostic indicator of severe hepatic dysfunction in Dress (Drug Reaction with Eosinophilia and Systemic Symptoms)
Authors: M.R. Ardern-Jones
Journal: British Journal of Dermatology (2013)

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) describes a heterogeneous group of severe adverse reactions to medications. The cutaneous phenotype has a number of guises, accompanied by a variety of systemic features including fever, haematological abnormalities and visceral involvement, most commonly the liver. Clinical markers of prognosis have not been identified.  OBJECTIVES: To assess the cutaneous signs and dermatopathological features of DRESS in order to identify potential prognostic markers.  METHODS: We reviewed the clinical features, dermatopathology and outcomes of 27 consecutive cases of DRESS presenting to a single unit.  RESULTS: Four distinct patterns of cutaneous involvement were identified: an urticated papular exanthem (13/27 patients), a morbilliform erythema (three of 27), an exfoliative erythroderma (three of 27) and an erythema multiforme-like (EM-like) reaction consisting of atypical targets (eight of 27). All patients mounted a fever, most developed lymphadenopathy (24/27) and peripheral eosinophilia (25/27) and the most common organ involved was the liver (27/27). Review of the dermatopathic features of patients with DRESS demonstrated a superficial spongiotic dermatitis in the majority of cases (16/27). A smaller number of cases showed basal cell vacuolar degeneration and necrotic keratinocytes (nine of 27). The patients with these biopsy findings more commonly had an EM-like cutaneous phenotype, and more severe hepatic involvement. Three patients died, two following failed liver transplants.  CONCLUSIONS: Our series is the first in which a detailed dermatological assessment has been made of consecutive patients presenting with DRESS, and the largest U.K. series to date. Our results suggest a possible prognostic role of the cutaneous and dermatopathic findings in DRESS in predicting the severity of visceral involvement in this syndrome. What's already known about this topic? Drug reaction with eosinophilia and systemic symptoms (DRESS) has a heterogeneous clinical presentation, with a skin eruption of variable morphology. DRESS carries considerable morbidity and mortality, usually hepatic in origin, although renal, pulmonary and pericardial involvement can be seen. What does this study add? The cutaneous phenotype in DRESS can be categorized as an urticated papular exanthem, a morbilliform erythema, exfoliative erythroderma or erythema multiforme-like (EM-like). An EM-like eruption DRESS may be prognostic of more severe hepatic involvement.
Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment.
Authors: S N Meydani, A H Lichtenstein, S Cornwall, M Meydani, B R Goldin, H Rasmussen, C A Dinarello, E J Schaefer
Journal: Journal of Clinical Investigation (1993)

Reductions in dietary fat, saturated fat, and cholesterol have been recommended to reduce the risk of heart disease in our society. The effects of these modifications on human cytokine production and immune responses have not been well studied. 22 subjects > 40 yr of age were fed a diet approximating that of the current American (14.1% of calories as saturated fatty acids, [SFA], 14.5% monounsaturated fatty acids [MUFA], 6.1% [n-6] polyunsaturated fatty acids [PUFA], 0.8% [n-3] PUFA, and 147 mg cholesterol/1,000 calories) for 6 wk, after which time they consumed (11 in each group) one of the two low-fat, low-cholesterol, high-PUFA diets based on National Cholesterol Education Panel (NCEP) Step 2 recommendations (4.0-4.5% SFA, 10.8-11.6% MUFA, 10.3-10.5% PUFA, 45-61 mg cholesterol/1,000 calories) for 24 wk. One of the NCEP Step 2 diets was enriched in fish-derived (n-3) PUFA (low-fat, high-fish: 0.54% or 1.23 g/d eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] [121-188 g fish/d]) and the other low in fish-derived (n-3) PUFA (low-fat, low-fish [0.13% or 0.27 g/d EPA and DHA] [33 g fish/d]). Measurements of in vivo and in vitro indexes of immune responses were taken after each dietary period. Long-term feeding of low-fat, low-fish diet enriched in plant-derived PUFA increased blood mononuclear cell mitogenic response to the T cell mitogen Con A, IL-1 beta, and TNF production and had no effect on delayed-type hypersensitivity skin response, IL-6, GM-CSF, or PGE2 production. In contrast, the low-fat, high-fish diet significantly decreased the percentage of helper T cells whereas the percentage of suppressor T cells increased. Mitogenic responses to Con A and delayed-type hypersensitivity skin response as well as the production of cytokines IL-1 beta, TNF, and IL-6 by mononuclear cells were significantly reduced after the consumption of the low-fat, high-fish diet (24, 40, 45, 35, and 34%, respectively; P < 0.05 by two-tailed Student's t test except for IL-1 beta and TNF, which is by one-tailed t test). Our data are consistent with the concept that the NCEP Step 2 diet that is high in fish significantly decreases various parameters of the immune response in contrast to this diet when it is low in fish. Such alterations may be beneficial for the prevention and treatment of atherosclerotic and inflammatory diseases but may be detrimental with regard to host defense against invading pathogens.