tbuckley/cabot-search huggingface dataset:
Specific Antagonism of PDGF Prevents Renal Scarring in Experimental Glomerulonephritis
Authors: TAMMO OSTENDORF, UTA KUNTER, HERMANN JOSEPH GRÖNE, FERDINAND BAHLMANN, HIROSHI KAWACHI, FUJIO SHIMIZU, KARL MARTIN KOCH, NEBOJSA JANJIC, JÜRGEN FLOEGE
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Glomerular mesangial cell proliferation and/or mesangial matrix accumulation characterizes many progressive renal diseases. Rats with progressive mesangioproliferative glomerulonephritis were treated from day 3 to day 7 after disease induction with a high-affinity oligonucleotide aptamerantagonist against platelet-derived growth factor-B chain (PDGF-B). In comparison with nephritic rats that received vehicle or a scrambled aptamer, treatment with the PDGF-B aptamer led to a significant reduction of mesangioproliferative changes, glomerular hypertrophy, podocyte damage, and glomerular macrophage influx on day 8. Both nephritic control groups subsequently developed progressive proteinuria and decreased renal function. On day 100, glomerulosclerosis, tubulointerstitial damage, glomerular and interstitial accumulation of types III and IV collagen, and overexpression of transforming growth factor-β were widespread. All of these chronic changes were prevented in rats that received the PDGF-B aptamer, and their functional and morphologic parameters on day 100 were largely indistinguishable from non-nephritic rats. These data provide the first evidence for a causal role of PDGF in the pathogenesis of renal scarring and point to a new, highly effective therapeutic approach to progressive, in particular mesangioproliferative, renal disease.
Raccoon Rabies Virus Variant Transmission Through Solid Organ Transplantation
Authors: Neil M. Vora
Journal: JAMA (2013)

IMPORTANCEThe rabies virus causes a fatal encephalitis and can be transmitted through tissue or organ transplantation.In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation.OBJECTIVES To investigate whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients from the same donor.DESIGN Organ donor and all transplant recipient medical records were reviewed.Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients.Viral ribonucleic acid was extracted from tissues and amplified for nucleoprotein gene sequencing for phylogenetic comparisons.MAIN OUTCOMES AND MEASURES Determination of whether the donor died from undiagnosed rabies and whether other organ recipients developed rabies. RESULTSIn retrospect, the donor's clinical presentation (which began with vomiting and upper extremity paresthesias and progressed to fever, seizures, dysphagia, autonomic dysfunction, and brain death) was consistent with rabies.Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor.The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9% identical across the entire N gene (1349/1350 nucleotides), thus confirming organ transplantation as the route of transmission.The 3 other organ recipients remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis (range, 0.3-40.8IU/mL).CONCLUSIONS AND RELEVANCE Unlike the 2 previous clusters of rabies virus transmission through solid organ transplantation, there was a long incubation period in the recipient who developed rabies, and survival of 3 other recipients without pretransplant rabies vaccination.Rabies should be considered in patients with acute progressive encephalitis of unexplained etiology, especially for potential organ donors.A standard evaluation of potential donors who meet screening criteria for infectious encephalitis should be considered, and risks and benefits for recipients of organs from these donors should be evaluated.
Increased Sodium-Lithium Countertransport Activity
Authors: Gianpaolo Zerbini, Daniela Gabellini, Dora Ruggieri, Anna Maestroni
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. An increased activity of sodium-lithium countertransport (SLC) is a common finding in patients who have essential hypertension. The evidence that a similar dysfunction is shared also by patients with type 1 diabetes and nephropathy has suggested the hypothesis that a predisposition to essential hypertension may be the factor that, along with hyperglycemia, underlies the development of diabetic nephropathy. Despite the initial enthusiasm surrounding the potential use of SLC activity as a marker for the early detection and treatment of individuals who are predisposed to hypertension and diabetic nephropathy, its use has been so far restricted to epidemiologic studies, as specificity and sensitivity of the test are still too low to justify any clinical use. The recent finding, however, that the measurement of kinetic parameters of SLC can significantly increase the power to discriminate among individuals with and without hypertension or diabetic nephropathy could be of help toward a future clinical use of the measurement of this membrane transport. A second major point relates to the possibility that SLC per se might be directly involved in the pathogenesis of essential hypertension and diabetic nephropathy. This case has never been fully tested, as the gene responsible for this membrane transport has been, until recently, unknown. The recent identification of an alternative splicing of the first isoform of Na-H exchange that mediates SLC activity should allow for a rapid comprehension of the role of this transport in the pathophysiology of essential hypertension and diabetic nephropathy.
Syphilitic Aortitis
Authors: H. ALEXANDER HEGGTVEIT
Journal: Circulation (1964)

The major clinical and pathologic features of 100 cases of syphilitic aortitis, autopsied from 1950 to 1960, are reviewed. Decreasing incidence, changing patterns of lesions, and reasons for the frequent failure to diagnose syphilitic heart disease are considered. Aortic insufficiency or aneurysm of the thoracic aorta, or both, accompanied by a history of syphilis or reactive serology are required to establish a definitive diagnosis. Syphilis still remains a real threat, and, until it is eradicated, it will continue to cause clinical and subclinical cardiovascular disease.
Normal sodium balance in dogs and in man
Authors: W. J. O'CONNOR
Journal: Cardiovascular Research (1977)

Journal Article Normal sodium balance in dogs and in man Get access W. J. O'CONNOR W. J. O'CONNOR From the Department of Physiology, University of Leeds Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 11, Issue 5, September 1977, Pages 375–408, https://doi.org/10.1093/cvr/11.5.375 Published: 01 September 1977
Requirement of Tumor Necrosis Factor Receptor–Associated Factor (Traf)6 in Interleukin 17 Signal Transduction
Authors: Ralf Schwandner, Kyoko Yamaguchi, Zhaodan Cao
Journal: The Journal of Experimental Medicine (2000)

Signaling through its widely distributed cell surface receptor, interleukin (IL)-17 enhances the transcription of genes encoding proinflammatory molecules. Although it has been well documented that IL-17 activates the transcription factor nuclear factor (NF)-kappaB and c-Jun NH(2)-terminal kinase (JNK), the upstream signaling events are largely unknown. Here we report the requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in IL-17-induced NF-kappaB and JNK activation. In embryonic fibroblasts (EFs) derived from TRAF6 knockout mice, IL-17 failed to activate the IkappaB kinases (IKKs) and JNK. Consequently, IL-17-induced IL-6 and intercellular adhesion molecule 1 expression in the TRAF6-deficient cells was abolished. Lack of TRAF6 appeared to be the sole defect responsible for the observed failure to respond to IL-17, because transient transfection of TRAF6 expression plasmid into the TRAF6-deficient cells restored IL-17-induced NF-kappaB activation in a luciferase reporter assay. Furthermore, the levels of IL-17 receptor (IL-17R) on the TRAF6-deficient EFs were comparable to those on the wild-type control cells. Defect in IL-17 response was not observed in TRAF2-deficient EFs. Moreover, when TRAF6 and IL-17R were coexpressed in 293 cells, TRAF6 coimmunoprecipitated with IL-17R. Together, these results indicate that TRAF6, but not TRAF2, is a crucial component in the IL-17 signaling pathway leading to proinflammatory responses.
Anticholinergic effects of disopyramide and quinidine on guinea pig myocardium. Mediation by direct muscarinic receptor blockade.
Authors: M J Mirro, A S Manalan, J C Bailey, A M Watanabe
Journal: Circulation Research (1980)

We studied the interaction of disopyramide, quinidine, and procainamide with cardiac muscarinic receptors. In electrophysiological experiments, the effects of disopyramide, quinidine, procainamide, and atropine were determined on spontaneously depolarizing guinea pig right atria (GPRA) both in the presence and absence of pharmacologically induced (physostigmine) cholinergic stimulation. All four agents demonstrated a concentration-dependent antagonism of the negative chronotropic effects of physostigmine. The order of anticholinergic potency was atropine greater than disopyramide greater than quinidine greater than procainamide. The ability of disopyramide to antagonize the physostigmine induced slowing was stereoselective, (+)disopyramide greater than (-)disopyramide. In contrast, the ability of quinidine to antagonize the negative chronotropic effects of physostigmine was non-stereoselective, quinidine = quinine. In parallel experiments, we studied the ability of disopyramide, quinidine, procainamide, and atropine to compete with the radiolabeled muscarinic receptor antagonist [3H] quinuclidinyl benzilate ([3H]QNB) for binding to muscarinic receptors in crude homogenates of GPRA and membrane vesicles from canine ventricular myocardium. All four agents inhibited [3H]QNB binding to muscarinic receptors. The order of anticholinergic potency determined by the receptor binding studies was identical to that determined by the physiological studies. The interaction of disopyramide with muscarinic receptors was stereoselective, (+)disopyramide &gt; (-)disopyramide. Quinidine was only slightly more potent than quinine in inhibiting [3H]QNB binding to muscarinic receptors. Interaction of antiarrhythmic drugs with muscarinic receptors satisfied criteria for a competitive interaction. The data from this study localize the anticholinergic effects of disopyramide and quinidine to the muscarinic receptor.
Nitric oxide stimulates heme oxygenase-1 gene transcription via the Nrf2/ARE complex to promote vascular smooth muscle cell survival
Authors: X LIU, K PEYTON, D ENSENAT, H WANG, M HANNINK, J ALAM, W DURANTE
Journal: Cardiovascular Research (2007)

Objective Previous studies from our laboratory and others found that NO is a potent inducer of heme oxygenase-1 (HO-1) gene transcription in vascular smooth muscle cells (SMC), however, the mechanism responsible for the induction of HO-1 gene expression has not been elucidated. In the present study, we determined the signaling pathway responsible for the induction of HO-1 and its biological significance.
Practice Patterns and Attitudes of Primary Care Providers and Barriers to Surveillance of Hepatocellular Carcinoma in Patients With Cirrhosis
Authors: Eimile Dalton-Fitzgerald, Jasmin Tiro, Pragathi Kandunoori, Ethan A. Halm, Adam Yopp, Amit G. Singal
Journal: Clinical Gastroenterology and Hepatology (2014)
Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors
Authors: Zhishen Ge, Qixian Chen, Kensuke Osada, Xueying Liu, Theofilus A. Tockary, Satoshi Uchida, Anjaneyulu Dirisala, Takehiko Ishii, Takahiro Nomoto, Kazuko Toh, Yu Matsumoto, Makoto Oba, Mitsunobu R. Kano, Keiji Itaka, Kazunori Kataoka
Journal: Biomaterials (2014)
Continuous vs Intermittent Heparin Therapy
Authors: E. Berry Hey
Journal: JAMA (1977)

To the Editor.—  I am concerned by two items in the article by Glazier and Crow (236:1365,1976). They document a 331/3% incidence of serious hemorrhage in patients receiving intermittent intravenous heparin sodium therapy. I regard that as an unusually and indeed unnecessarily high level of hemorrhage for this technique. I believe that the explanation for this stems from the fact that their patients who were bleeding were being given dosages of heparin sodium that averaged greater than 9,000 units every six hours. The average age of these bleeding patients was 67 years.  The second item that concerns me is the 5% incidence of pulmonary embolism in the patients treated with continuous heparin therapy.  It has been my experience in a very large group of patients treated with 5,000 units of heparin every six hours that major hemorrhage is an exceedingly rare event, regardless of the results of their clotting studies;
Trends in the epidemiology of asthma in England: a national study of 333,294 patients
Authors: Colin R Simpson, Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (2010)

Summary Background Observations in the UK at the end of the last century found increasing trends of asthma prevalence over time. However, it has been reported that the number of new cases of asthma presenting to general practice has declined, especially among younger children. Aim To study national trends in the epidemiology of asthma. Methods A cross-sectional observation analysis was performed using the QRESEARCH database, which is one of the world's largest national aggregated health databases containing records from 422 English practices yielding 30 million patient-years of observation. Data was extracted on 333,294 individuals with a recorded diagnosis of asthma and calculated annual age–sex standardized incidence, lifetime period prevalence and asthma-related prescribing rates for each year from 2001–2005. Results The incidence rate of asthma decreased in all patients (2001: 6.9 (95% confidence intervals [CI] 6.8–7.0); 2005: 5.2 (95% CI 5.1–5.3) per 1000 patient-years, p&lt;0.001), but most particularly in children under 5 years of age (–38.4%) where a decrease in the lifetime prevalence of asthma (–34.3%) was also found. However, the lifetime prevalence rate of asthma for adults increased (15–44 years: 23.3%; 45–64 years: 27.7%; &gt;65 years: 21.5%) with an estimated 5,658,900 (95% CI 5,639,700–5,678,200) or approximately one person in nine having being diagnosed with asthma in England. The number of asthma-related prescriptions also increased over the study period (17.1%), such that in 2005 an estimated 32,577,300 (95%CI 32,531,600–32,623,000) prescriptions were issued. Conclusions This large national study reveals that the rate of new diagnoses of asthma appears to have passed its peak; however, the number of adults with a lifetime asthma diagnosis continues to rise. Whether these trends are genuine or are a result of the introduction of incentives and guidelines to improve identification and recording of asthma or changing diagnostic trends is a question with important public health implications and one, therefore, that warrants detailed further enquiry.
Relationship of serum markers of cartilage metabolism to imaging and clinical outcome measures of knee joint structure
Authors: P. A. Berry, R. A. Maciewicz, A. E. Wluka, M. D. Downey-Jones, A. Forbes, C. J. Hellawell, F. M. Cicuttini
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Biomarkers of cartilage metabolism have prognostic potential. <h3>Objective</h3> To examine whether serum cartilage biomarkers, cartilage oligomeric matrix protein (COMP), N-propeptide of type IIA procollagen (PIIANP), type II collagen breakdown product (collagen type-II cleavage (C2C)) predict cartilage volume loss and knee joint replacement. <h3>Methods</h3> 117 subjects with knee osteoarthritis (OA) had MRI at baseline and 2 years. Cartilage biomarkers were measured at baseline. Change in knee cartilage volume over 2 years and knee joint replacement over 4 years was determined. The population was divided into subgroups with high or low cartilage biomarkers (based on biomarker levels greater than or equal to, or less than, the mean, respectively). The relationships between biomarkers and outcome measures were examined in the whole population, and separately in marker subgroups. <h3>Results</h3> The relationship between cartilage biomarkers and cartilage volume loss was not linear across the whole population. In the low (regression coefficient B=–9.7, 95% CI –0.01 to 0.003, p=0.01), but not high (B=–0.46, 95% CI –8.9 to 8.0, p=0.92) COMP subgroup, COMP was significantly associated with a reduced rate of medial cartilage volume loss (p for difference between groups=0.05). Similarly, in the low (B=–8.2, 95% CI –12.9 to –3.5, p=0.001) but not high (B=2.6, 95% CI –3.3 to 8.5, p=0.38) PIIANP subgroup, PIIANP was associated with a significantly reduced rate of medial volume cartilage loss (p for difference=0.003). C2C was not significantly associated with rate of cartilage volume loss. PIIANP was associated with a reduced risk of joint replacement (odds ratio (OR)=0.28, 95% CI 0.10 to 0.93, p=0.04). <h3>Conclusion</h3> Cartilage biomarkers may be used to identify subgroups among those with clinical knee OA in whom disease progresses at different rates. This may facilitate our understanding of the pathogenesis of disease and allow us to differentiate phenotypes of disease within a heterogeneous knee OA population.
The p270 (<i>ARID1A/SMARCF1</i>) Subunit of Mammalian SWI/SNF-Related Complexes Is Essential for Normal Cell Cycle Arrest
Authors: Norman G. Nagl, Antonia Patsialou, Dale S. Haines, Peter B. Dallas, George R. Beck, Elizabeth Moran
Journal: Cancer Research (2005)

Abstract Mammalian SWI/SNF-related complexes are ATPase-powered nucleosome remodeling assemblies crucial for proper development and tissue-specific gene expression. The ATPase activity of the complexes is also critical for tumor suppression. The complexes contain seven or more noncatalytic subunits; only one of which, hSNF5/Ini1/BAF47, has been individually identified as a tumor suppressor thus far. The noncatalytic subunits include p270/ARID1A, which is of particular interest because tissue array analysis corroborated by screening of tumor cell lines indicates that p270 may be deficient in as many as 30% of renal carcinomas and 10% of breast carcinomas. The complexes can also include an alternative ARID1B subunit, which is closely related to p270, but the product of an independent gene. The respective importance of p270 and ARID1B in the control of cell proliferation was explored here using a short interfering RNA approach and a cell system that permits analysis of differentiation-associated cell cycle arrest. The p270-depleted cells fail to undergo normal cell cycle arrest on induction, as evidenced by continued synthesis of DNA. These lines fail to show other characteristics typical of arrested cells, including up-regulation of p21 and down-regulation of cyclins. The requirement for p270 is evident separately in both the up-regulation of p21 and the down-regulation of E2F-responsive products. In contrast, the ARID1B-depleted lines behaved like the parental cells in these assays. Thus, p270-containing complexes are functionally distinct from ARID1B-containing complexes. These results provide a direct biological basis to support the implication from tumor tissue screens that deficiency of p270 plays a causative role in carcinogenesis.
Atran's biodiversity parser: Doubts about hierarchy and autonomy
Authors: Eugene S. Hunn
Journal: Behavioral and Brain Sciences (1998)

Atran argues that an autonomous ethnobiological information-processing module exists. This module imputes a “deep causal essence” to folk-biological taxa and uses a hierarchy of taxonomic ranks. I argue that Atran's own data suggest that rank is not an essential feature of the ethnobiological module, and that ethnobiological causal essences may be generalized to other domains and vice versa, limiting its autonomy.
Chronic Uremia Stimulates LDL Carbamylation and Atherosclerosis
Authors: Eugene O. Apostolov, Debarti Ray, Alena V. Savenka, Sudhir V. Shah, Alexei G. Basnakian
Journal: Journal of the American Society of Nephrology (2010)

Carbamylated LDL (cLDL) is a potential atherogenic factor in chronic kidney disease (CKD). However, whether elevated plasma cLDL associates with atherosclerosis in vivo is unknown. Here, we induced CKD surgically in apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-fat diet to promote the development of atherosclerosis. These mice had two- to threefold higher plasma levels of both oxidized LDL (oxLDL) and cLDL compared with control mice. Oral administration of urea increased cLDL approximately eightfold in ApoE(-/-) mice subjected to unilateral nephrectomy and a high-fat diet, but oxLDL did not rise. Regardless of the model, the uremic mice with high plasma cLDL had more severe atherosclerosis as measured by intravital ultrasound echography and en face aortic staining of lipid deposits. Furthermore, cLDL accumulated in the aortic wall and colocalized with ICAM-1 and macrophage infiltration. In summary, these data demonstrate that elevated plasma cLDL may represent an independent risk factor for uremia-induced atherosclerosis.
Strut Position, Blood Flow, and Drug Deposition
Authors: Brinda Balakrishnan, Abraham R. Tzafriri, Philip Seifert, Adam Groothuis, Campbell Rogers, Elazer R. Edelman
Journal: Circulation (2005)

Background— The intricacies of stent design, local pharmacology, tissue biology, and rheology preclude an intuitive understanding of drug distribution and deposition from drug-eluting stents (DES). Methods and Results— A coupled computational fluid dynamics and mass transfer model was applied to predict drug deposition for single and overlapping DES. Drug deposition appeared not only beneath regions of arterial contact with the strut but surprisingly also beneath standing drug pools created by strut disruption of flow. These regions correlated with areas of drug-induced fibrin deposition surrounding DES struts in porcine coronary arteries. Fibrin deposition immediately distal to individual isolated drug-eluting struts was twice as great as in the proximal area and for the stent as a whole was greater in distal segments than proximal segments. Adjacent and overlapping stent struts increased computed arterial drug deposition by far less than the sum of their combined drug load. In addition, drug eluted from the abluminal stent strut surface accounted for only 11% of total deposition, whereas, remarkably, drug eluted from the adluminal surface accounted for 43% of total deposition. Thus, local blood flow alterations and location of drug elution on the strut were far more important in determining arterial wall drug deposition and distribution than were drug load or arterial wall contact with coated strut surfaces. Conclusions— Simulations that coupled strut configurations with flow dynamics correlated with in vivo effects and revealed that drug deposition occurs less via contact between drug coating and the arterial wall than via flow-mediated deposition of blood-solubilized drug.