tbuckley/cabot-search huggingface dataset:
Chronic Exposure to Lead Chromate Causes Centrosome Abnormalities and Aneuploidy in Human Lung Cells
Authors: Amie L. Holmes, Sandra S. Wise, Sarah J. Sandwick, Wilma L. Lingle, Vivian C. Negron, W. Douglas Thompson, John Pierce Wise
Journal: Cancer Research (2006)

Abstract Hexavalent chromium [Cr(VI)] compounds are established human lung carcinogens. The carcinogenicity of Cr(VI) is related to its solubility, with the most potent carcinogens being the insoluble particulate Cr(VI) compounds. However, it remains unknown why particulate Cr(VI) is more carcinogenic than soluble Cr(VI). One possible explanation is that particulates may provide more chronic exposures to chromate over time. We found that aneuploid cells increased in a concentration- and time-dependent manner after chronic exposure to lead chromate. Specifically, a 24-hour lead chromate exposure induced no aneugenic effect, whereas a 120-hour exposure to 0.5 and 1 μg/cm2 lead chromate induced 55% and 60% aneuploid metaphases, respectively. We also found that many of these aneuploid cells were able to continue to grow and form colonies. Centrosome defects are known to induce aneuploidy; therefore, we investigated the effects of chronic lead chromate exposure on centrosomes. We found that centrosome amplification in interphase and mitotic cells increased in a concentration- and time-dependent manner with 0.5 and 1 μg/cm2 lead chromate for 120 hours, inducing aberrant centrosomes in 18% and 21% of interphase cells and 32% and 69% of mitotic cells, respectively; however, lead oxide did not induce centrosome amplification in interphase or mitotic cells. There was also an increase in aberrant mitosis after chronic exposure to lead chromate with the emergence of disorganized anaphase and mitotic catastrophe. These data suggest that one possible mechanism for lead chromate–induced carcinogenesis is through centrosome dysfunction, leading to the induction of aneuploidy. (Cancer Res 2006; 66(8): 4041-8)
IgG4 multiorgan lymphoproliferative syndrome as a differential diagnosis of primary Sjogren's syndrome in men?
Authors: G. Nocturne, S. Pavy, T. Lazure, Y. Taoufik, C. Miceli, X. Mariette
Journal: Annals of the Rheumatic Diseases (2011)

In 1888, Mikulicz-Radecki reported a case exhibiting bilateral, painless and symmetrical swellings of the lacrimal, parotid and submandibular glands. In 1953, Morgan and Castleman suggested that Mikulicz disease (MD) should be reconsidered as one of the manifestations of primary Sjogren's syndrome (pSS) as they shared many histopathological characteristics. But recently, several groups demonstrated that MD may differ from pSS. Actually, MD may partly be an IgG4-related systemic disease, the other components of which are still undelineated and include autoimmune pancreatitis, chronic sclerosing sialoadenitis, Riedel's thyroiditis, some cases of cholangitis, retroperitoneal fibrosis.1 Masaki defined a new clinical entity, the IgG4 multiorgan lymphoproliferative syndrome (MOLPS), which includes these manifestations.2 It is characterised by hyper-IgG4 γ-globulinaemia and IgG4 plasma cell infiltration. There are a number of differences with …
Molecular Identification of Canine Podocalyxin-Like Protein 1 as a Renal Tubulogenic Regulator
Authors: Hsin-Yuan Cheng, Yu-Yu Lin, Chun-Ying Yu, Jen-Yau Chen, Kuo-Fang Shen, Wei-Ling Lin, Hsin-Kai Liao, Yu-Ju Chen, Chen-Hsuan Liu, Victor Fei Pang, Tzuu-Shuh Jou
Journal: Journal of the American Society of Nephrology (2005)

GP135 is an apical membrane protein expressed in polarized MDCK epithelial cells. When cultured in three-dimensional collagen gel, MDCK cells form branching tubules in response to hepatocyte growth factor stimulation in a manner that simulates the embryonic renal development. During this process, GP135 displays transient loss of membranous localization but reappears at the cell surface when nascent lumen emerges from the developing tubules. Despite being used for decades as the canonical hallmark of apical surface, the molecular identity and the significance of the dynamic expression of GP135 during the tubulogenic process remain elusive. For exploring the function of GP135, the full-length cDNA encoding GP135 was obtained. Sequence alignments and features analysis confirm GP135 as a canine homolog of podocalyxin, confirming the finding of an earlier independent study. Immunohistochemical assays on canine kidney sections identified both glomerular and tubular distribution of GP135 along the nephron. Mutant MDCK cells expressing siRNA targeted at two regions of GP135 show defects in hepatocyte growth factor-induced tubulogenesis. Re-expression of full-length and an O-linked glycosylation abbreviated construct of GP135 could recapitulate the tubulogenesis process lacking in siRNA knockdown cells; however, a deletion construct devoid of the cytoplasmic domain failed to rescue the phenotype. In summary, the data identify the MDCK apical domain marker GP135 as a tubular form of podocalyxin and provide evidence for its importance in renal tubulogenesis.
Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997–2004)
Authors: Anjo J Veerman, Willem A Kamps, Henk van den Berg, Eva van den Berg, Jos PM Bökkerink, Marrie CA Bruin, Marry M van den Heuvel-Eibrink, Carin M Korbijn, Elisabeth T Korthof, Karin van der Pal, Theo Stijnen, Margreet H van Weel Sipman, J Fransje van Weerden, Elisabeth R van Wering, Anna van der Does-van den Berg
Journal: The Lancet Oncology (2009)
Angiotensin II and myosin light-chain phosphorylation contribute to the stretch-induced slow force response in human atrial myocardium
Authors: J. Kockskamper, M. Khafaga, M. Grimm, A. Elgner, S. Walther, A. Kockskamper, D. von Lewinski, H. Post, M. Grossmann, H. Dorge, P. A. Gottlieb, F. Sachs, T. Eschenhagen, F. A. Schondube, B. Pieske
Journal: Cardiovascular Research (2008)

AimsStretch is an important regulator of atrial function. The functional effects of stretch on human atrium, however, are poorly understood. Thus, we characterized the stretch-induced force response in human atrium and evaluated the underlying cellular mechanisms.
Sarcoidosis-related Mortality in the United States from 1988 to 2007
Authors: Jeffrey J. Swigris, Amy L. Olson, Tristan J. Huie, Evans R. Fernandez-Perez, Joshua Solomon, David Sprunger, Kevin K. Brown
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

It has been nearly 20 years since sarcoidosis mortality was examined at the population level in the United States.
Prognosis Factors of Primary Gastric Non-Hodgkin'S Lymphoma in Central Region of Tunisia
Authors: Imtinene Belaid, Imene Chabchoub, Nesrine Mejri, Faten Ezzairi, Rim Chafai, Olfa Gharbi, Leila Ben Fatma, Makrem Hochlaf, Slim Ben Ahmed
Journal: Annals of Oncology (2013)
Early Progression of Diabetic Nephropathy Correlates With Methylglyoxal-Derived Advanced Glycation End Products
Authors: Paul J. Beisswenger, Scott K. Howell, Gregory B. Russell, Michael E. Miller, Stephen S. Rich, Michael Mauer
Journal: Diabetes Care (2013)

Increased advanced glycation end products (AGEs) and oxidation products (OPs) are proposed to lead to progression of diabetic nephropathy (DN). We investigated the relationship between AGEs, OPs, and progression of DN in 103 subjects with type 1 diabetes participating in the Natural History of Diabetic Nephropathy Study.Mean age of subjects was 17.6±7.4 years, and mean duration of diabetes was 8.3±4.9 years. All patients were normoalbuminuric. Change in glomerular basement membrane (GBM) width from baseline to 5 years, measured using electron micrographs of renal biopsies, was our primary end point, and mesangial fractional volume was a secondary end point. Fast progressors (FPs) were defined as those in the upper quartile of GBM change, and the remaining patients were classified as slow progressors (SPs). AGEs (3-deoxyglucosone and methylglyoxal hydroimidazolones [MGHI]), carboxymethyl lysine (CML), carboxyethyl lysine (CEL), and OPs (methionine sulfoxide and 2-aminoadipic acid) were measured at year 5 by liquid chromatography/triple-quadruple mass spectroscopy on 10-K plasma filtrates.We found that MGHI, CEL, and CML levels were significantly higher in FPs relative to SPs. No product predicted mesangial expansion. A model containing only HbA1c accounted for 4.7% of GBM width variation, with the total variability explained by the model increasing to 11.6% when MGHI, CEL, and CML were added to the regression model (7.9% increase). MGHI was a significant independent predictor of FP. Using a logistic regression model to relate each biomarker to the probability of a subject's classification as an FP, CML, CEL, and MGHI, but not HbA1c, showed a significant relationship to the probability of FP.The results suggest that these three major AGEs may be early indicators of progression of important DN lesions.
Polyubiquitin binding to ABIN1 is required to prevent autoimmunity
Authors: Sambit K. Nanda, Ram K.C. Venigalla, Alban Ordureau, Janet C. Patterson-Kane, David W. Powell, Rachel Toth, J. Simon C. Arthur, Philip Cohen
Journal: The Journal of Experimental Medicine (2011)

The protein ABIN1 possesses a polyubiquitin-binding domain homologous to that present in nuclear factor κB (NF-κB) essential modulator (NEMO), a component of the inhibitor of NF-κB (IκB) kinase (IKK) complex. To address the physiological significance of polyubiquitin binding, we generated knockin mice expressing the ABIN1[D485N] mutant instead of the wild-type (WT) protein. These mice developed all the hallmarks of autoimmunity, including spontaneous formation of germinal centers, isotype switching, and production of autoreactive antibodies. Autoimmunity was suppressed by crossing to MyD88−/− mice, demonstrating that toll-like receptor (TLR)–MyD88 signaling pathways are needed for the phenotype to develop. The B cells and myeloid cells of the ABIN1[D485N] mice showed enhanced activation of the protein kinases TAK, IKK-α/β, c-Jun N-terminal kinases, and p38α mitogen-activated protein kinase and produced more IL-6 and IL-12 than WT. The mutant B cells also proliferated more rapidly in response to TLR ligands. Our results indicate that the interaction of ABIN1 with polyubiquitin is required to limit the activation of TLR–MyD88 pathways and prevent autoimmunity.
Lateral internal sphincterotomy is not redundant in the era of glyceryl trinitrate therapy for chronic anal fissure
Authors: M Jonas, D N Lobo, A M Gudgeon
Journal: Journal of the Royal Society of Medicine (1999)

Lateral internal sphincterotomy has been the standard treatment for chronic anal fissure, but fissure healing rates of up to 80% with topical glyceryl trinitrate (GTN) treatment have suggested that this operation may become redundant. We evaluated the results of topical treatment of chronic anal fissures with 0.2% GTN for 6 weeks in the outpatient clinical setting, outside the confines of a randomized clinical trial. The role of lateral internal sphincterotomy in the GTN era was also assessed. GTN induced fissure healing in 21 of 49 consecutive patients. Fissures healed spontaneously in 2 patients who discontinued GTN because of headache. Lateral internal sphincterotomy was performed in 26 patients who had persistent symptoms after 6 weeks of GTN therapy. At the 6-week post-sphincterotomy review, all fissures had healed and there were no complications. In this study topical GTN for treatment of chronic anal fissure in the outpatient setting was not as effective as demonstrated in controlled clinical trials. Lateral internal sphincterotomy is still a good therapeutic option, especially in patients not responding to GTN.
Standardized Endpoint Definitions for Transcatheter Aortic Valve Implantation Clinical Trials
Authors: Martin B. Leon, Nicolo Piazza, Eugenia Nikolsky, Eugene H. Blackstone, Donald E. Cutlip, Arie Pieter Kappetein, Mitchell W. Krucoff, Michael Mack, Roxana Mehran, Craig Miller, Marie-angéle Morel, John Petersen, Jeffrey J. Popma, Johanna J.M. Takkenberg, Alec Vahanian, Gerrit-Anne van Es, Pascal Vranckx, John G. Webb, Stephan Windecker, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2011)

To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health. Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials. The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the U.S. Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included: 1) respect for the historical legacy of surgical valve guidelines; 2) identification of pathophysiological mechanisms associated with clinical events; 3) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended. Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.
Adaptive servoventilation in diastolic heart failure and Cheyne-Stokes respiration
Authors: T. Bitter, N. Westerheide, L. Faber, D. Hering, C. Prinz, C. Langer, D. Horstkotte, O. Oldenburg
Journal: European Respiratory Journal (2009)

A high prevalence of nocturnal Cheyne-Stokes respiration (CSR) has been documented in patients with heart failure with normal left ventricular ejection fraction (HFNEF). The aim of the present study was to investigate the effects of adaptive servoventilation (ASV) for treatment of CSR in these patients. In 60 patients with HFNEF, defined according to current European Society of Cardiology guidelines, CSR was documented by polysomnography (apnoea/hypopnoea index (AHI) of >15 events x h(-1)). ASV treatment was offered to all patients; 21 initially rejected treatment, withdrew from treatment or presented noncompliant during follow-up (controls), whereas ongoing ASV therapy was initiated in 39 patients (ASV group). Echocardiography, cardiopulmonary exercise testing and measurement of N-terminal-pro-brain natriuretic peptide were performed at baseline and follow-up (11.6+/-3 months). ASV therapy led to a significant reduction in AHI, longest apnoea and hypopnoea length, maximum and mean oxygen desaturation by pulse oximetry, percentage of study time with an oxygen saturation of <90% and arousal index. In addition, significant positive effects could be confirmed on absolute and predicted peak oxygen consumption, oxygen consumption at the individual aerobic-anaerobic threshold, oxygen pulse, as well as left atrial size, and transmitral flow patterns (mean early diastolic lengthening velocity and the ratio of peak early Doppler mitral inflow velocity to this lengthening velocity). ASV effectively attenuates CSR in patients with HFNEF and improves heart failure symptoms and cardiac function. Whether or not this is accompanied by an improved prognosis remains to be determined.
Placental Growth Factor Regulates Cardiac Adaptation and Hypertrophy Through a Paracrine Mechanism
Authors: Federica Accornero, Jop H. van Berlo, Matthew J. Benard, John N. Lorenz, Peter Carmeliet, Jeffery D. Molkentin
Journal: Circulation Research (2011)

Rationale: Paracrine growth factor-mediated crosstalk between cardiac myocytes and nonmyocytes in the heart is critical for programming adaptive cardiac hypertrophy in which myocyte size, capillary density, and the extracellular matrix function coordinately. Objective: To examine the role that placental growth factor (PGF) plays in the heart as a paracrine regulator of cardiac adaptation to stress stimulation. Methods and Results: PGF is induced in the heart after pressure-overload stimulation, where it is expressed in both myocytes and nonmyocytes. We generated cardiac-specific and adult inducible PGF-overexpressing transgenic mice and analyzed Pgf −/− mice to examine the role that this factor plays in cardiac disease and paracrine signaling. Although PGF transgenic mice did not have a baseline phenotype or a change in capillary density, they did exhibit a greater cardiac hypertrophic response, a greater increase in capillary density, and increased fibroblast content in the heart in response to pressure-overload stimulation. PGF transgenic mice showed a more adaptive type of cardiac growth that was protective against signs of failure with pressure overload and neuroendocrine stimulation. Antithetically, Pgf −/− mice rapidly died of heart failure within 1 week of pressure overload, they showed an inability to upregulate angiogenesis, and they showed significantly less fibroblast activity in the heart. Mechanistically, we show that PGF does not have a direct effect on cardiomyocytes but works through endothelial cells and fibroblasts by inducing capillary growth and fibroblast proliferation, which secondarily support greater cardiac hypertrophy through intermediate paracrine growth factors such as interleukin-6. Conclusions: PGF is a secreted factor that supports hypertrophy and cardiac function during pressure overload by affecting endothelial cells and fibroblasts that in turn stimulate and support the myocytes through additional paracrine factors.
International Union of Pharmacology. XLII. Compendium of Voltage-Gated Ion Channels: Cyclic Nucleotide-Modulated Channels
Authors: Franz Hofmann, Martin Biel, U. Benjamin Kaupp
Journal: Pharmacological Reviews (2003)

This summary article presents an overview of the molecular relationships among the voltage-gated cyclic nucleotide-modulated channels and a standard nomenclature for them, which is derived from the <i>IUPHAR Compendium of Voltage-Gated Ion Channels.</i>1 The complete Compendium, including data tables for each member of the cyclic nucleotide-modulated channel family can be found at http://www.iuphar-db.org/iuphar-ic/.
Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin
Authors: J. Nakafusa, Y. Narisawa, T. Shinogi, K. Taira, T. Tanaka, T. Inoue, N. Misago
Journal: British Journal of Dermatology (2006)

Hair discs are known to contain a large number of Merkel cells and are ideal for investigating Merkel cell biology. Hair follicles, which are important elements of hair discs, undergo unique cyclical morphological and biological changes.To define the relationships between the number and the morphology of Merkel cells within the hair disc in association with the hair cycle on rat back skin.Merkel cells in hair discs were observed three-dimensionally using immunohistochemistry. Epidermal sheets were incubated with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs were clearly demonstrated as whole shapes and were counted under a light microscope.Merkel cells in hair discs increased during the early to middle phase of anagen and decreased during the middle phase of anagen to catagen and telogen in perinatal and postnatal rat back skin. We observed the morphological variation of Merkel cells in hair discs of rat back skin, and consequently divided them into two subtypes at the light microscopic level: the oval type and the dendritic type. The number of oval-type Merkel cells was not markedly affected by the hair cycle. In contrast, the number of dendritic-type Merkel cells markedly changed with the hair cycle.This difference of the hair cycle dependency between oval and dendritic-type Merkel cells suggests some functional differences, such as a secretory function, related to the hair cycle.
Cough in the community: a cross sectional survey and the relationship to gastrointestinal symptoms
Authors: A C Ford, D Forman, P Moayyedi, A H Morice
Journal: Thorax (2006)

The prevalence and severity of chronic cough in the community is uncertain. In a large population of representative normal subjects, we explored the relationship between self-reported cough severity and frequency, and factors known to be related to the aetiology of chronic cough. In particular, we have examined the relative association between cough and symptoms of gastrointestinal disease.A cross-sectional survey was undertaken in 36 general practices with subjects randomly selected from practice computer databases. Baseline lifestyle and demographic characteristics were recorded. Participants were asked how often in the previous 2 months they had experienced bouts or spasms of coughing. Cough symptom status was dichotomised into symptomatic using a cut off of bouts or spasms of coughing at a frequency of between once a week and once a day or above. Gastrointestinal data were collected using validated methodology.Questionnaires were sent to 6416 subjects and 4003 (62%) responded. The prevalence of chronic cough was 12%, and was severe in 7%. Following multivariate analysis, regurgitation (OR 1.71; 99% CI 1.20 to 2.45) and irritable bowel syndrome (OR 2.00; 99% CI 1.47 to 2.72) were strong predictors of cough. Smoking (OR 1.61; 99% CI 1.18 to 2.19), declining social class (OR 1.63; 99% CI 1.04 to 2.57), and quality of life at baseline (OR 1.63; 99% CI 1.13 to 2.35) were also significantly associated.Chronic cough is a common symptom in the general population. Its strong association with gastrointestinal disease may have aetiological significance.
HOW IS THE EARLY DIAGNOSIS OF PULMONARY TUBERCULOSIS TO BE MADE?
Authors: J. S. Dick
Journal: BMJ (1917)

C m lmJoU 741 for them free of charge under those Acts; h-lowever, such cases can be multiplied indefinitely wlhere people consider it more desirable to employ a handy-woman wlho remains in residence during the lying-in, period, and washes and liouselieeps for the household, wllile the unremunerated disiensary doctor is compelled to take over the work, and also the opprobritum of the untrained midwives' too- frequently-fatal mistakes.Where in the bill are we empowered to expel untrained women from the charge of a " Poor Law emnergency case " and substitute our trained lnurse?No suclh provision is made.Is the Local Government Board prepared to