tbuckley/cabot-search huggingface dataset:
Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel
Authors: Gheun-Ho Kim, Jay Wook Lee, Yun Kyu Oh, Hye Ryun Chang, Kwon Wook Joo, Ki Young Na, Jae-Ho Earm, Mark A. Knepper, Jin Suk Han
Journal: Journal of the American Society of Nephrology (2004)

Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na(+) concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na(+) transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry. After feeding male Sprague-Dawley rats Li chloride-containing rat diet for 4 wk, HCTZ or vehicle was infused subcutaneously via osmotic minipump. Urine output was significantly decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats. Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed that HCTZ treatment caused a significant partial recovery in AQP2 abundance from Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings with the immunoblot results in both cortex and medulla. The abundances of thiazide-sensitive NaCl co-transporter and alpha-epithelial sodium channel were increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular weight of gamma-epithelial sodium channel from 85 to 70 kD, consistent with previously demonstrated aldosterone stimulation. The upregulation of AQP2 and distal renal Na(+) transporters in response to HCTZ treatment may account for the antidiuretic action of HCTZ in NDI.
Impaired fc-mediated mononuclear phagocyte system clearance in HLA-DR2 and MT1-positive healthy young adults.
Authors: R P Kimberly, A Gibofsky, J E Salmon, M Fotino
Journal: The Journal of Experimental Medicine (1983)

Normal individuals with an HLA haplotype containing either DR2, MT1, or B8/DR3 are more likely to have abnormally prolonged Fc receptor-mediated mononuclear phagocyte system (MPS) clearance of IgG-sensitized autologous erythrocytes than their normal counterparts without such haplotypes. Although measurement of Fc receptor binding by rosette formation and saturable IgG aggregate binding revealed no differences among groups, Fc receptor-mediated phagocytosis of IgG-sensitized bovine erythrocytes by monocytes was decreased in the DR2-positive and MT1-positive individuals. The basal in vivo MPS clearance in normal individuals may be immunogenetically determined and may reflect differences in phagocytic rates.
Human anti-DNA antibody: reference standards for diagnosis and management of systemic lupus erythematosus.
Authors: J Holian, I D Griffiths, D N Glass, R N Maini, J T Scott
Journal: Annals of the Rheumatic Diseases (1975)

A technique for the measurement of DNA binding activity of sera is described which uses primary internal reference standards in a Farr assay. This allows the DNA binding activity of test sera to be measured in relation to the reference standards and the results are expressed as units/ml. The use of this standardized assay has led to diminished interassay variation and close interlaboratory correlation, and has provided a clinically useful test. In survey using the standardized assay, normal sera were found to have binding activity which did not exceed 15 units/ml; 71% of patients with systemic lupus erythematosus (SLE) had levels greater than 25 units/ml; while only 8% of patients with diseases other than SLE had levels above 25 units/ml. Values between 15 and 25 units/ml appeared to have little diagnostic significance.
P2-310: Phase II trial of adjuvant chemotherapy with bi-weekly carboplatin plus paclitaxel in patients with completely resected non-small cell lung cancer
Authors: Kenji Sugio, Akira Nagashima, Ryoichi Nakanishi, Hisanobu Sakata, Kozo Nakanishi, Masakazu Sugaya, Manabu Yasuda, Mitsuhiro Takenoyama, Takeshi Hanagiri, Kosei Yasumoto
Journal: Journal of Thoracic Oncology (2007)
Comparison of Rheumatoid (Ankylosing) Spondylitis and Crippling Fluorosis
Authors: C. L. Steinberg, D. E. Gardner, F. A. Smith, H. C. Hodge
Journal: Annals of the Rheumatic Diseases (1955)

Crippling fluorosis and rheumatoid (ankylosing) spondylitis present a confusing similarity; both are * This paper is based in part on work performed under contract with the U.S.
Fatty Acid Composition of Tissue Cultured Breast Carcinoma: Effect of Stearoyl-Coa Desaturase-1 (SCD-1) Inhibitor
Authors: M. Darabi, F. Mohammadzadeh, M. Darabi, S. Fayezi, G. Mosayebi, M. Shaaker, A. Mehdizadeh
Journal: Annals of Oncology (2014)
Respiratory syncytial virus infection of airway epithelial cells, in vivo and in vitro, supports pulmonary antibody responses by inducing expression of the B cell differentiation factor BAFF
Authors: P S McNamara, A M Fonceca, D Howarth, J B Correia, J R Slupsky, R E Trinick, W Al Turaiki, R L Smyth, B F Flanagan
Journal: Thorax (2012)

<h3>Background</h3> The mechanisms regulating antibody expression within the human lung during airway infection are largely unknown. In this study, our objectives were to determine if infection with respiratory syncytial virus (RSV) upregulates expression of the B cell differentiation factors A proliferation inducing ligand (APRIL) and B cell activating factor of the TNF family (BAFF), if this is a common feature of viral airway infection, and how this is regulated in human airway epithelial cells. <h3>Methods</h3> We measured BAFF and APRIL protein expression in bronchoalveolar lavage (BAL) fluid from infants with severe RSV disease, and healthy control children, and in nasopharyngeal aspirates from preschool children with other single respiratory viral infections. We also measured mRNA expression in bronchial brushings from RSV-infected infants, and in RSV-infected paediatric primary airway epithelial cell cultures (pAEC). Beas-2B cell cultures were used to examine mechanisms regulating BAFF expression. <h3>Results</h3> BAFF protein and mRNA were elevated (in marked contrast with APRIL) in BAL and bronchial brushings, respectively, from RSV-infected infants. BAFF protein was also found in upper airway secretions from children with human metapneumovirus, H1N1, bocavirus, rhinovirus, RSV and <i>Mycoplasma pneumoniae</i> infection. BAFF mRNA and protein were expressed following in vitro RSV infection of both pAEC and Beas-2B cultures, with mRNA expression peaking 12-h postinfection. BAFF induction was blocked by addition of a neutralising anti-interferon-β antibody or palivizumab. <h3>Conclusions</h3> BAFF, produced through an interferon-β-dependant process, is a consistent feature of airway infection, and suggests a role for the airway epithelia in supporting protective antibody and B cell responses in the lung.
The natural history of Crohn's disease: who holds the crystal ball?
Authors: Gert Van Assche
Journal: Gut (2012)

to speculate that supplementation of HGF might directly enhance the repopulation capacity of the c-Met competent donor hepatocytes, and indirectly improve the microenvironment of the recipient liver.In summary, Kaldenbach and his colleagues have significantly advanced our knowledge of the role of HGF/c-Met signalling pathway in hepatocyte transplantation.Whereas the absolute requirement for the HGF/c-Met pathway in the donor hepatocytes is firmly established, the issue of the usefulness of inhibiting the c-Met pathway in the recipient liver requires further exploration.
Intra-articular co-infection by Borrelia burgdorferi and Chlamydia trachomatis
Authors: N Putschky
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> <i>Chlamydia trachomatis</i> and <i>Borrelia burgdorferi</i>infections are frequently the cause of unexplained oligoarthritis, as shown by identification of bacteria specific DNA in joint material from patients with reactive arthritis, Lyme arthritis, and undifferentiated oligoarthritis. The aim of this study was to determine whether the two organisms occur simultaneously in joint material from patients with arthritis. <h3>METHODS</h3> Seventy six patients with unexplained arthritis were prospectively studied. Synovial fluid was obtained from all patients and examined for DNA from<i>C trachomatis</i> and <i>B burgdorferi</i> using specific polymerase chain reaction (PCR) protocols. Data concerning prior genitourinary infection or a history of tick bite were recorded and serum antibodies to<i>C trachomatis</i> and <i>B burgdorferi</i> were determined. <h3>RESULTS</h3> Six patients (8%) had DNA from both <i>C trachomatis</i> and<i>B burgdorferi</i> in the same synovial fluid specimen (mean leucocyte count 11.925/mm<sup>3</sup>, 65% granulocytes). These patients (four men, two women; mean age 33.7 years) all had oligoarthritis of the knee, ankle, or both (mean disease duration 11.3 months). From the history and serological examination, four patients had some evidence of actual or previous infection with one or other of the bacteria, while the other two patients had a positive serological test for <i>Chlamydia</i>only. <h3>CONCLUSIONS</h3> DNA from two different microorganisms which are known to be triggering agents for arthritis may be present simultaneously in joint material from patients with unexplained oligoarthritis. This finding raises the question as to whether, in such cases, one or both bacteria contribute to the pathogenesis of the disease or whether they are only innocent bystanders.
Regional oxygen saturation of small arteries and veins in the canine myocardium.
Authors: H R Weiss, A K Sinha
Journal: Circulation Research (1978)

Oxygen saturation of small arteries and veins (20-500 micron) was determined microspectrophotometrically in the hearts of 12 pentobarbital-anesthetized open-chest dogs. Hearts were removed, quick frozen in liquid propane, and O2 saturation was determined in blood vessels on a regional basis between and within ventricular walls. No significant differences existed in arterial O2 saturation between right, left, and septal walls or regionally within any wall by depth or in base-to-apex comparisons. Although there was variation in arterial saturation, it was independent of vessel size. Arteries were followed by serial section into the left ventricular wall for distances up to 7.5 mm without significant saturation change. The average venous saturations of the right, septal, and left ventricular walls were not significantly different. No regional differences in venous saturation were found within any ventricular wall in comparisons between base and apex. In the left ventricle, subepicardial venous saturation (29.8%) was significantly higher than subendocardial saturation (16.4%). In veins traced from the surface, saturation decreased with depth. Greater variability of saturation was found in small compared to large veins. The greater O2 extraction in the subendocardium may indicate a higher O2 consumption than in the subepicardium.
Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease
Authors: E. J. Kim, B. M. Elicker, F. Maldonado, W. R. Webb, J. H. Ryu, J. H. Van Uden, J. S. Lee, T. E. King, H. R. Collard
Journal: European Respiratory Journal (2009)

Interstitial lung disease is a common manifestation of rheumatoid arthritis; however, little is known about factors that influence its prognosis. The aim of the present study was to determine whether or not the usual interstitial pneumonia pattern found on high-resolution computed tomography (HRCT) is of prognostic significance in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients with RA-ILD were identified retrospectively (n = 82). The relationship of a definite usual interstitial pneumonia pattern on HRCT to survival was determined and compared to that in a cohort of patients with radiologically diagnosed idiopathic pulmonary fibrosis (n = 51). A definite usual interstitial pneumonia pattern was seen in 20 (24%) out of 82 patients with RA-ILD. These patients showed worse survival than those without this pattern (median survival 3.2 versus 6.6 yrs), and a similar survival to those with idiopathic pulmonary fibrosis. On multivariate analysis, a definite usual interstitial pneumonia pattern on HRCT was associated with worse survival (hazard ratio of 2.3). Analysis of specific HRCT features demonstrated that traction bronchiectasis and honeycomb fibrosis were associated with worse survival (hazard ratio of 2.6 and 2.1, respectively). Female sex (hazard ratio of 0.30) and a higher baseline diffusing capacity of the lung for carbon monoxide (hazard ratio of 0.96) were associated with better survival. A definite usual interstitial pneumonia pattern on HRCT has important prognostic implications in RA-ILD.
Purification of human gamma interferon receptors by sequential affinity chromatography on immobilized monoclonal antireceptor antibodies and human gamma interferon.
Authors: M Aguet, G Merlin
Journal: The Journal of Experimental Medicine (1987)

mAbs against human IFN-gamma (huIFN-gamma) receptors were obtained by immunizing a BALB/c mouse with eluates from immobilized recombinant huIFN-gamma (rhuIFN-gamma) on which lysates of enriched Raji cell membranes had been adsorbed. mAbs were selected for competitive inhibition of receptor binding of 125I-labeled rhuIFN-gamma. The following additional properties suggest that these antibodies are specific for huIFN-gamma receptors: they bind to the surface of human cells expressing IFN-gamma receptors but not to heterologous cells; this binding is inhibited competitively by addition of rhuIFN-gamma; the number of binding sites revealed by direct binding of 125I-labeled rhuIFN-gamma correlates with the amount of antigen recognized by the mAbs on different cell lines. A Triton X-100 extract of a membrane-enriched fraction of human Raji cells was affinity purified with these mAbs and the eluates from such columns were further purified on immobilized rhuIFN-gamma. As revealed by SDS-PAGE, the final eluate contained two major protein bands with approximate Mr of 90,000 (p90) and 50,000 (p50), respectively. Both proteins were able to specifically bind 125I-labeled rhuIFN-gamma upon electroblotting to nitrocellulose. This binding could be inhibited by the huIFN-gamma receptor mAbs, suggesting that the same epitopes are recognized on p90, p50, and on the cell surface. Therefore, these proteins most likely represent at least a part of huIFN-gamma receptors.
Activating HER2 Mutations in HER2 Gene Amplification Negative Breast Cancer
Authors: Ron Bose, Shyam M. Kavuri, Adam C. Searleman, Wei Shen, Dong Shen, Daniel C. Koboldt, John Monsey, Nicholas Goel, Adam B. Aronson, Shunqiang Li, Cynthia X. Ma, Li Ding, Elaine R. Mardis, Matthew J. Ellis
Journal: Cancer Discovery (2012)

Data from 8 breast cancer genome-sequencing projects identified 25 patients with HER2 somatic mutations in cancers lacking HER2 gene amplification. To determine the phenotype of these mutations, we functionally characterized 13 HER2 mutations using in vitro kinase assays, protein structure analysis, cell culture, and xenograft experiments. Seven of these mutations are activating mutations, including G309A, D769H, D769Y, V777L, P780ins, V842I, and R896C. HER2 in-frame deletion 755-759, which is homologous to EGF receptor (EGFR) exon 19 in-frame deletions, had a neomorphic phenotype with increased phosphorylation of EGFR or HER3. L755S produced lapatinib resistance, but was not an activating mutation in our experimental systems. All of these mutations were sensitive to the irreversible kinase inhibitor, neratinib. These findings show that HER2 somatic mutation is an alternative mechanism to activate HER2 in breast cancer and they validate HER2 somatic mutations as drug targets for breast cancer treatment.We show that the majority of HER2 somatic mutations in breast cancer patients are activating mutations that likely drive tumorigenesis. Several patients had mutations that are resistant to the reversible HER2 inhibitor lapatinib, but are sensitive to the irreversible HER2 inhibitor, neratinib. Our results suggest that patients with HER2 mutation–positive breast cancers could benefit from existing HER2-targeted drugs.
Practical experience with the implementation of an athlete's biological profile in athletics, cycling, football and swimming
Authors: M Zorzoli, A Pipe, P Y Garnier, M Vouillamoz, J Dvorak
Journal: British Journal of Sports Medicine (2014)

The introduction of the athlete's biological passport (ABP) has been a milestone in the fight against doping. The ABP is a collection of measurements of different biological parameters influenced by the administration of doping agents through the time and for each athlete. Two different modules have been developed and validated so far: the haematological module, which aims to identify enhancement of oxygen transport, including use of erythropoiesis-stimulating agents and any form of blood transfusion or manipulation, which became effective in 2010; and the steroidal module, which intends to detect the use of endogenous anabolic androgenic steroids when administered exogenously and other anabolic agents, which was introduced in 2014. Prior to the implementation of the haematological module, it is important to define an athlete’s testing pool on whom to collect blood and/or urine in-competition and out-of-competition (for the steroidal module, this is irrelevant because all collected urine samples will be subjected to analysis for the steroidal variables) and to be compliant with the strict requirements of the World Anti-Doping Agency ABP Operating Guidelines. The established individual profile can be used either to target traditional antidoping tests (recombinant erythropoietins, or homologous blood transfusion tests for the haematological module; isotope ratio mass spectrometry (IRMS) for the steroidal module) or to support an antidoping rule violation due to the use of a forbidden substance or method. In this article, we present the experience of four major International Federations which have implemented an ABP programme, focusing on the haematological module. They constitute examples which could be followed by other antidoping organisations wishing to introduce this new, efficient and innovative antidoping tool.
THE SERUM BACTERICIDAL SYSTEM: ULTRASTRUCTURAL CHANGES IN NEISSERIA MENINGITIDIS EXPOSED TO NORMAL RAT SERUM
Authors: John Swanson, Irving Goldschneider
Journal: The Journal of Experimental Medicine (1969)

Exposure of meningococci to the bactericidal system of normal rat serum initiates a series of ultrastructural changes that accompany death of the organism. These morphological alterations consist of complement-dependent holes in the cell wall outer membrane, edema of the periplasmic space and cytoplasm, and accumulation of fibrillar material in and on the cell wall. Dissolution of the dense line and rupture of the cytoplasmic membrane also occur in meningococci exposed to normal rate serum. These latter two changes, however, are not seen in meningococci that are killed by bentonite-absorbed (lysozyme-deficient) serum, nor are they invariably present when other serum-susceptible organisms (N. catarrhalis and Herellea sp.) are treated with normal rat serum. The pattern of development of edema in serum-treated meningococci suggests that the cell wall outer membrane, mucopeptide layer, and cytoplasmic membrane act synergistically to maintain osmotic equilibrium of the bacterium. Death of the bacterium seems related to alteration of permeability following injury to the outer membrane. Holes are demonstrable, by negative straining, in the outer membrane of the meningococcal cell wall after exposure to the bactericidal effects of rat serum. The lesions are 110 A average greatest diameter and depend on the presence of antibody and complement for their formation. In addition, 82 A diameter holes are present in the walls of normal, untreated meningococci. The relation of complement-dependent holes to the smaller, naturally occurring holes is not known.
Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: The role of the anhepatic period
Authors: Minke C. Bakker, Herold J. Metselaar, Theo N. Groenland, Maria J. Gomes, Eduard A.R. Knot, Eric J. Hesselink, Solco W. Schalm, Jeanne Stibbe, Onno T. Terpstra
Journal: Hepatology (1992)

The major cause of the increased tissue-type plasminogen activator activity during orthotopic liver transplantation is still unclear. Both the lack of hepatic clearance of tissue-type plasminogen activator in the anhepatic period and increased endothelial release from the graft on reperfusion have been proposed as the major causes. Heterotopic liver transplantation avoids the resection of the host liver and is a useful model to help differentiate between these two possibilities. In this study the fibrinolytic system was evaluated in 10 orthotopic liver transplantations, 18 heterotopic liver transplantations and a control group of 10 partial hepatic resections. A marked increment in tissue-type plasminogen activator activity, from 0.2 to 5.2 IU/ml (p less than 0.02), was observed during the anhepatic period of orthotopic liver transplantation, which rapidly normalized after reperfusion. In contrast, tissue-type plasminogen activator activity levels remained normal in heterotopic liver transplantation and partial hepatic resections. In orthotopic liver transplantation and in heterotopic liver transplantation no increase occurred in tissue-type plasminogen activator activity after reperfusion. The first venous hepatic outflow after reperfusion did not contain elevated tissue-type plasminogen activator activity levels. Plasma degradation products of fibrin and fibrinogen increased during the anhepatic period of orthotopic liver transplantation (from 2.60 to 8.80 micrograms/ml [p less than 0.008] and from 0.40 to 1.60 micrograms/ml [p less than 0.04], respectively) and remained elevated thereafter. In heterotopic liver transplantation and partial hepatic resections these levels remained low. In conclusion, the lack of hepatic clearance during the anhepatic period is probably the most important factor in the evolution of increased tissue-type plasminogen activator activity during orthotopic liver transplantation.