tbuckley/cabot-search huggingface dataset:
Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model
Authors: Y. Imamura, K. Yanagihara, Y. Fukuda, Y. Kaneko, M. Seki, K. Izumikawa, Y. Miyazaki, Y. Hirakata, T. Sawa, J. P. Wiener-Kronish, S. Kohno
Journal: European Respiratory Journal (2007)

<i>Pseudomonas aeruginosa</i> is one of the most important pathogens in patients with chronic airway conditions, such as cystic fibrosis and diffuse panbronchiolitis. Type III secretion system-mediated virulence factors contribute to the lung damage in chronic <i>P. aeruginosa</i> infection. The effects of the anti-PcrV immunoglobulin (Ig)G, which blocks the type III secretion system, were evaluated in a mouse model of chronic <i>P. aeruginosa</i> infection. On bacteriological examination, anti-PcrV IgG showed no bactericidal effects. On bronchoalveolar lavage fluid (BALF) analysis, total cell number and neutrophil ratios in the anti-PcrV IgG-treated groups were lower than those in the control group. In addition, macrophage inflammatory protein-2, tumour necrosis factor-α, and interleukin-β concentrations in BALF were lower in the anti-PcrV IgG-treated groups when compared with controls. Plasma anti-PcrV IgG titre was elevated after administration of anti-PcrV IgG. Although plasma titre decreased gradually, a significant concentration was maintained during the experimental period. These data suggest that anti-PcrV immunoglobulin G reduces the inflammatory reaction caused by chronic <i>Pseudomonas aeruginosa</i> respiratory infection and may be useful in treating respiratory diseases.
Penicillin by Intra-oral Drip
Authors: G. R. Royston
Journal: BMJ (1947)

The ease with which fluids injected distally from the groin level pass into the femoral veins suggests that high injection of the thigh segment is unwise.There is much less risk below the knee.The large perforating vein immediately below the knee shown in one phlebogram appears to be inconstant.The remaining deep communications are small.In our opinion operative treatment of varicose veins should consist of adequate ligation with, if necessary, distal injection from knee level of not more than 5 ml. of sclerosing solution.
Circulatory function and hepatorenal syndrome in cirrhosis
Authors: Luis Ruiz‐del‐Arbol, Alberto Monescillo, Carlos Arocena, Paz Valer, Pere Ginès, Víctor Moreira, José María Milicua, Wladimiro Jiménez, Vicente Arroyo
Journal: Hepatology (2005)

The pathogenic mechanism of hepatorenal syndrome is not well established. We investigated the circulatory function in cirrhosis before and after the development of hepatorenal syndrome. Systemic and hepatic hemodynamics and the activity of endogenous vasoactive systems were measured in 66 patients who had cirrhosis with tense ascites and normal serum creatinine levels; measurements were repeated at follow-up in 27 cases in whom hepatorenal syndrome had developed. At baseline, mean arterial pressure and cardiac output were significantly higher, and hepatic venous pressure gradient, plasma renin activity, and norepinephrine concentration were significantly lower in patients who did not develop hepatorenal syndrome compared with those presenting with this complication. Peripheral vascular resistance was decreased to the same extent in the two groups. Plasma renin activity and cardiac output were the only independent predictors of hepatorenal syndrome. Hepatorenal syndrome occurred in the setting of a significant reduction in mean arterial pressure (83 ± 9 to 75 ± 7 mmHg; P < .001), cardiac output (6.0 ± 1.2 to 5.4 ± 1.5 L/min; P < .01), and wegded pulmonary pressure (9.2 ± 2.6 to 7.5 ± 2.6 mmHg; P < .001) and an increase in plasma renin activity (9.9 ± 5.2 to 17.5 ± 11.4 ng/mL · hr; P < .001), norepinephrine concentration (571 ± 241 to 965 ± 502 pg/mL; P < .001), and hepatic venous pressure gradient. No changes were observed in peripheral vascular resistance. In conclusion, these data indicate that hepatorenal syndrome is the result of a decrease in cardiac output in the setting of a severe arterial vasodilation. (HEPATOLOGY 2005.)
Airway reactivity and neuroimmune relationships in animal model of air born irritants induced symptoms - Role of trigeminal TRPA1 channels
Authors: Zuzana Biringerova, Mariana Brozmanova, Silvia Gavliakova, Martina Sutovska, Sona Franova, Marian Adamkov, Milos Tatar, Jana Plevkova
Journal: European Respiratory Journal (2012)

Air born pollutants modulate functions of airways. Many experimental models use inhalation of air born irritants containing aerosols to mimic environmental exposure however, most exposed part is the nose. The aim of our study was to assess the general effects and modulation of airway defensive reflexes in animal model by selective nasal challenges with TRPA1 agonist AITC – allylisothiocyanate. TRPA1 is known to be relevant for most air born irritants.  15 male Dunkin Hartly guinea pigs were repeatedly exposed to 10mM AITC, 15μl administered into both nostrils and nasal symptoms, cough, specific airway resistance (Saw) and bronchoalveolar lavages (BAL) were analyzed afterwards.  Nasal administration of 10 mM AITC induces reproducible nasal symptoms, sneezing, discharge, crackles and conjunctival reaction. Also, nasal application of 10mM AITC induces spontaneous rise of Saw measured by Pennock9s method in vivo and increases Saw after inhalation of methacholin (p
Relationship Of Immune Response To Endotoxin And Candida To Clinical Status Of Patients With Combined Bacterial And Candidal Periodontitis
Authors: V.A. Beloglazov, N.S. Lukojanova, A.I. Gordienko, N.V. Khimich, A.A. Bakova, I.V. DuBuske, L.M. DuBuske
Journal: Journal of Allergy and Clinical Immunology (2007)
Interaction between PLA2R1 and HLA-DQA1 Variants Associates with Anti-PLA2R Antibodies and Membranous Nephropathy
Authors: Jicheng Lv, Wanyin Hou, Xujie Zhou, Gang Liu, Fude Zhou, Na Zhao, Ping Hou, Minghui Zhao, Hong Zhang
Journal: Journal of the American Society of Nephrology (2013)

Risk alleles at genome loci containing phospholipase A2 receptor 1 (PLA2R1) and HLA-DQA1 closely associate with idiopathic membranous nephropathy (IMN) in the European population, but it is unknown whether a similar association exists in the Chinese population and whether high-risk alleles promote the development of anti-PLA2R antibodies. Here, we genotyped 2132 Chinese individuals, including 1112 patients with IMN and 1020 healthy controls, for three single nucleotide polymorphisms (SNPs) within PLA2R1 and three SNPs within HLA genes. We also selected 71 patients, with varying genotypes, to assess for circulating anti-PLA2R antibody and for PLA2R expression in glomeruli. Three SNPs within PLA2R1 and one SNP within HLA-DQA1 strongly associated with IMN, and we noted gene–gene interactions involving these SNPs. Furthermore, these risk alleles strongly associated with the presence of anti-PLA2R antibodies and glomerular PLA2R expression. Among individuals who carried risk alleles for both genes, 73% had anti-PLA2R antibodies and 75% expressed PLA2R in glomeruli. In contrast, among individuals who carried protective genotypes of both genes, none had anti-PLA2R antibodies and glomerular expression of PLA2R was weak or absent. In conclusion, the interaction between PLA2R1 and HLA-DQA1 risk alleles associates with the development of IMN in the Chinese population. Individuals carrying risk alleles are predisposed to the generation of circulating anti-PLA2R autoantibodies, which may contribute to the development of IMN.
Histoplasma capsulatum modulates the acidification of phagolysosomes.
Authors: L G Eissenberg, W E Goldman, P H Schlesinger
Journal: The Journal of Experimental Medicine (1993)

The phagolysosome is perhaps the most effective antimicrobial site within macrophages due both to its acidity and to its variety of hydrolytic enzymes. Few species of pathogens survive and multiply in these vesicles. However, one strategy for microbial survival would be to induce a higher pH within these organelles, thus interfering with the activity of many lysosomal enzymes. Altering the intravesicular milieu might also profoundly influence antigen processing, antimicrobial drug delivery, and drug activity. Here we report the first example of an organism proliferating within phagolysosomes that maintain a relatively neutral pH for a sustained period of time. We inoculated P388D1 macrophages with fluorescein isothiocyanate (FITC)-labeled Histoplasma capsulatum or zymosan. Using the ratio of fluorescence excitations at 495 and 450 nm, we determined that vesicles containing either virulent or avirulent FITC-labeled H. capsulatum yeasts had a pH one to two units higher than vesicles containing either zymosan or methanol-killed H. capsulatum. The difference in pH remained stable for at least 5.5 h postinoculation. Longer-term studies using cells preincubated with acridine orange indicated that phagolysosomes containing live Histoplasma continued to maintain a relatively neutral pH for at least 30 h. Many agents raise the pH of multiple vesicles within the same cell. In contrast, H. capsulatum affects only the phagolysosome in which it is located; during coinoculation of cells with unlabeled Histoplasma and labeled zymosan, organelles containing zymosan still acidified normally. Similarly, unlabeled zymosan had no influence on the elevated pH of vesicles housing labeled Histoplasma. Thus, zymosan and Histoplasma were segregated into separate phagolysosomes that responded independently to their phagocytized contents. This localized effect might reflect an intrinsic difference between phagosomes housing the two particle types, active buffering by the microbe, or altered ion transport across the phagolysosomal membrane such that acidification is inhibited.
Serum Selenium and the Risk of Cancer, by Specific Sites: Case-Control Analysis of Prospective Data&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Nomura A, Heilbrun Lk, Morris Js, Stemmermann Gn
Journal: JNCI Journal of the National Cancer Institute (1987)

From 1971 to 1975, serum specimens were obtained from 6,860 men of Japanese ancestry in Hawaii. Since then, the following numbers of newly diagnosed cases with epithelial cancer have been identified: 82 colon, 71 lung, 66 stomach, 32 rectum, and 29 urinary bladder. The stored sera of the 280 cases and of 293 randomly selected controls were tested to determine their levels of selenium. There was no association of serum selenium with lung, stomach, or rectal cancer. An increase in relative risk (RR) was noted only for subjects in the lowest quintile of selenium values, as compared to the RR for subjects in the highest quintile, for colon (RR = 1.8) and urinary bladder cancer (RR = 3.1), but neither of these RR estimates was statistically significant (P = .09 and P = .07, respectively). Further work is needed to determine whether the antioxidant properties of selenium protect against specific types of cancer.
Ventricular Septal Rupture Secondary to Myocardial Infarction
Authors: Kanzui Matsui
Journal: JAMA (1981)

Twenty-four patients underwent operation for ventricular septal rupture secondary to acute myocardial infarction. There were 14 hospital survivors (58%) and two late deaths (8%). There were eight hospital deaths (62%) of 13 patients referred in cardiogenic shock, but only two deaths (18%) of 11 patients not in shock at time of referral. All 12 current survivors showed clinical improvement, and 11 of them are in New York Heart Association functional class I or II. Eleven patients had bedside catheterization with a balloon catheter and were operated on immediately thereafter, and eight survived (73%) with no late deaths at five years. With formal heart catheterization followed by operation, there were only six survivors of 13 operated on (46%).
Noninvasive Detection of Myocardial Ischemia From Perfusion Reserve Based on Cardiovascular Magnetic Resonance
Authors: Nidal Al-Saadi, Eike Nagel, Michael Gross, Axel Bornstedt, Bernhard Schnackenburg, Christoph Klein, Waldemar Klimek, Helmut Oswald, Eckart Fleck
Journal: Circulation (2000)

Myocardial perfusion reserve can be noninvasively assessed with cardiovascular MR. In this study, the diagnostic accuracy of this technique for the detection of significant coronary artery stenosis was evaluated.In 15 patients with single-vessel coronary artery disease and 5 patients without significant coronary artery disease, the signal intensity-time curves of the first pass of a gadolinium-DTPA bolus injected through a central vein catheter were evaluated before and after dipyridamole infusion to validate the technique. A linear fit was used to determine the upslope, and a cutoff value for the differentiation between the myocardium supplied by stenotic and nonstenotic coronary arteries was defined. The diagnostic accuracy was then examined prospectively in 34 patients with coronary artery disease and was compared with coronary angiography. A significant difference in myocardial perfusion reserve between ischemic and normal myocardial segments (1.08+/-0.23 and 2.33+/-0.41; P<0.001) was found that resulted in a cutoff value of 1.5 (mean minus 2 SD of normal segments). In the prospective analysis, sensitivity, specificity, and diagnostic accuracy for the detection of coronary artery stenosis (> or =75%) were 90%, 83%, and 87%, respectively. Interobserver and intraobserver variabilities for the linear fit were low (r=0.96 and 0.99).MR first-pass perfusion measurements yielded a high diagnostic accuracy for the detection of coronary artery disease. Myocardial perfusion reserve can be easily and reproducibly determined by a linear fit of the upslope of the signal intensity-time curves.
Apelin and vascular dysfunction in type 2 diabetes
Authors: O GRISK
Journal: Cardiovascular Research (2007)

See article by Zhong et al.  [13]  (pages 388–395) in this issue. 

The apelin receptor APJ belongs to the family of seven-transmembrane domain receptors and is coupled to inhibitory G-proteins [1,2]. Apelin is synthesized as a 77 amino acid pre-pro-peptide that can be cleaved into fragments of different sizes that activate APJ [1,2]. Apelin peptides have been shown to affect many biological functions in mammals including the neuroendocrine, cardiovascular, and immune systems [1]. It can act via autocrine, paracrine, endocrine, and exocrine signalling [1].

In the cardiovascular system apelin has been shown to increase cardiac contractility when administered in pharmacological doses [3]. The implications of this effect have been discussed recently in this journal [4]. Exogenous apelin lowers arterial pressure in mice and rats [5,6]. This effect is largely due to vasodilation as a consequence of apelin-induced activation of the endothelial nitric oxide synthase (eNOS) [5]. However, in conscious sheep low doses of apelin induced no significant alterations in arterial pressure [7]. At a higher dose a clear biphasic arterial pressure response was observed consisting of initial hypotension followed by hypertension [7]. This was accompanied by reciprocal heart rate changes that were most likely baroreflex mediated [7]. These data suggest … 

*Tel.: +49 3834 8619300; fax: +49 3834 8618310. Email address: grisko{at}uni-greifswald.de
Measurement of whole unstimulated salivary flow in the diagnosis of Sjogren's syndrome.
Authors: P M Speight, A Kaul, R D Melsom
Journal: Annals of the Rheumatic Diseases (1992)

The criteria for a clinical diagnosis of Sjögren9s syndrome remain controversial and vary widely from study to study. With respect to the oral component it is considered necessary to use some form of objective test, but many of those available are not suitable for use in a busy clinical situation. The purpose of this study was to evaluate a simple method for measuring the whole unstimulated salivary flow. Twenty five patients with Sjögren9s syndrome, 69 young control subjects, 20 age matched normal older control subjects and 20 patients with rheumatoid arthritis without Sjögren9s syndrome had their salivary flows measured. Whole unstimulated salivary flows in the young control subjects were higher than in all other groups. Patients with primary Sjögren9s syndrome had lower flows than either the older controls or the rheumatoid patients. Among the patients with Sjögren9s syndrome 52% had a flow of 0.1 ml/min or less compared with only 8% of age matched controls. The positive predictive value of this low flow was 81%. It is concluded that whole unstimulated salivary flows of 0.1 ml/min or less are highly specific for xerostomia. When interpreted in the context of all the clinical findings whole unstimulated salivary flows are useful for diagnosing the oral component of Sjögren9s syndrome.
How to Understand Divergent Views on Bipolar Disorder in Youth
Authors: Gabrielle A. Carlson, Daniel N. Klein
Journal: Annual Review of Clinical Psychology (2014)

There are two divergent viewpoints on the phenomenology and outcome of bipolar I (BP I) disorder in youth. Disparities evolved as unintended consequences from investigators' inconsistencies both in translating the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III, DSM-III-R, and DSM-IV criteria and in operationalizing them differently in their standardized assessments. Rates of conservatively diagnosed BP I are lower both in community studies of youths than in adults and from liberally defined BP I in youths. Rates of co-occurring attention-deficit hyperactivity disorder (ADHD) are lower in conservatively than liberally defined children and adolescents with BP I. Rates of both BP I and of ADHD are lower in offspring of BP I probands, and outcome more closely approximates that of adults with BP I in conservatively versus liberally defined children and teens with BP I. Both perspectives can claim evidence for reliability and validity that support their positions. However, the samples are so different that it is difficult to compare studies conducted from these different perspectives.
PubNet: a flexible system for visualizing literature derived networks.
Authors: Shawn M Douglas, Gaetano T Montelione, Mark Gerstein
Journal: Genome biology (2005)

Abstract We have developed PubNet, a web-based tool that extracts several types of relationships returned by PubMed queries and maps them into networks, allowing for graphical visualization, textual navigation, and topological analysis. PubNet supports the creation of complex networks derived from the contents of individual citations, such as genes, proteins, Protein Data Bank (PDB) IDs, Medical Subject Headings (MeSH) terms, and authors. This feature allows one to, for example, examine a literature derived network of genes based on functional similarity.
Dormant Tumor Cells Develop Cross-Resistance to Apoptosis Induced by CTLs or Imatinib Mesylate via Methylation of Suppressor of Cytokine Signaling 1
Authors: Aurore Saudemont, Abdelbasset Hamrouni, Philippe Marchetti, Jizhong Liu, Nathalie Jouy, Dominique Hetuin, Francesco Colucci, Bruno Quesnel
Journal: Cancer Research (2007)

Abstract In the BCR/ABL DA1-3b mouse model of acute myelogenous leukemia, dormant tumor cells may persist in the host in a state of equilibrium with the CD8+ CTL-mediated immune response by actively inhibiting T cells. Dormant tumor cells also show a progressive decrease of suppressor of cytokine signaling 1 (SOCS1) gene expression and a deregulation of the Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) pathway due to methylation of the SOCS1 gene. Dormant tumor cells were more resistant to apoptosis induced by specific CTLs, but resistance decreased when SOCS1 expression was restored via demethylation or gene transfer. AG490 JAK2 inhibitor decreased the resistance of dormant tumor cells to CTLs, but MG132 proteasome inhibitor was effective only in SOCS1-transfected cells. Thus, SOCS1 regulation of the JAK/STAT pathways contributes to the resistance of tumor cells to CTL-mediated killing. Resistance of dormant tumor cells to apoptosis was also observed when induced by irradiation, cytarabine, or imatinib mesylate, but was reduced by SOCS1 gene transfer. This cross-resistance to apoptosis was induced by interleukin 3 (IL-3) overproduction by dormant tumor cells and was reversed with an anti–IL-3 antibody. Thus, tumor cells that remain dormant for long periods in the host in spite of a specific CTL immune response may deregulate their JAK/STAT pathways and develop cross-resistance to various treatments through an IL-3 autocrine loop. These data suggest possible new therapeutic targets to eradicate dormant tumor cells. [Cancer Res 2007;67(9):4491–8]
Cyclooxygenase-2–Derived Prostaglandin F <sub>2α</sub> Mediates Endothelium-Dependent Contractions in the Aortae of Hamsters With Increased Impact During Aging
Authors: Siu Ling Wong, Fung Ping Leung, Chi Wai Lau, Chak Leung Au, Lai Ming Yung, Xiaoqiang Yao, Zhen-Yu Chen, Paul M. Vanhoutte, Maik Gollasch, Yu Huang
Journal: Circulation Research (2008)

Hypertension and vascular dysfunction result in the increased release of endothelium-derived contracting factors (EDCFs), whose identity is poorly defined. We tested the hypothesis that endothelial cyclooxygenase (COX)-2 can generate EDCFs and identified the possible EDCF candidate. Changes in isometric tension of aortae of young and aged hamsters were recorded on myograph. Real-time changes in intracellular calcium concentrations ([Ca 2+ ] i ) in native aortic endothelial cells were measured by imaging. Endothelium-dependent contractions were triggered by acetylcholine (ACh) after inhibition of nitric oxide production and they were abolished by COX-2 but not COX-1 inhibitors or by thromboxane–prostanoid receptor antagonists. 2-Aminoethoxydiphenyl borate (cation channel blocker) eliminated endothelium-dependent contractions and ACh-stimulated rises in endothelial cell [Ca 2+ ] i . RT-PCR and Western blotting showed COX-2 expression mainly in the endothelium. Enzyme immunoassay and high-performance liquid chromatography-coupled mass spectrometry showed release of prostaglandin (PG)F 2α and prostacyclin (PGI 2 ) increased by ACh; only PGF 2α caused contraction at relevant concentrations. COX-2 expression, ACh-stimulated contractions, and vascular sensitivity to PGF 2α were augmented in aortae from aged hamsters. Human renal arteries also showed thromboxane–prostanoid receptor–mediated ACh- or PGF 2α -induced contractions and COX-2–dependent release of PGF 2α . The present study demonstrates that PGF 2α , derived from COX-2, which is localized primarily in the endothelium, is the most likely EDCF underlying endothelium-dependent, thromboxane–prostanoid receptor–mediated contractions to ACh in hamster aortae. These contractions involved increases in endothelial cell [Ca 2+ ] i . The results support a critical role of COX-2 in endothelium-dependent contractions in this species with an increased importance during aging and, possibly, a similar relevance in humans.
SECONDHAND TOBACCO SMOKE IN NEVER SMOKERS IS A SIGNIFICANT RISK FACTOR FOR CORONARY ARTERY CALCIFICATION
Authors: Harvey S. Hecht, David Yankelewitz, Claudia Henschke, Rowena Yip, Paolo Boffetta, Shemesh Shemesh, Matthew Cham, Jagat Narula
Journal: Journal of the American College of Cardiology (2013)