tbuckley/cabot-search huggingface dataset:
Circulating Platelet-Activating Factor Is Primarily Cleared by Transport, Not Intravascular Hydrolysis by Lipoprotein-Associated Phospholipase A <sub>2</sub> / PAF Acetylhydrolase
Authors: Jinbo Liu, Rui Chen, Gopal K. Marathe, Maria Febbraio, Weilin Zou, Thomas M. McIntyre
Journal: Circulation Research (2010)

The phospholipid platelet-activating factor (PAF) stimulates all cells of the innate immune system and numerous cardiovascular cells. A single enzyme (plasma PAF acetylhydrolase [PAF-AH] or lipoprotein-associated phospholipase [Lp-PL]A(2)) in plasma hydrolyzes PAF, but significant controversy exists whether its action is pro- or antiinflammatory and accordingly whether its inhibition will slow cardiovascular disease.We sought to define how PAF and related short-chain oxidized phospholipids turnover in vivo and the role of PAF acetylhydrolase/Lp-PLA(2) in this process.[(3)H-acetyl]PAF was hydrolyzed by murine or human plasma (t(1/2), 3 and 7 minutes, respectively), but injected [(3)H-acetyl]PAF disappeared from murine circulation more quickly (t(1/2), <30 seconds). [(3)H]PAF clearance was unchanged in PAF receptor(-/-) animals, or over the first 2 half-lives in PAF-AH(-/-) animals. [(3)H]PAF turnover was reduced by coinjecting excess unlabeled PAF or an oxidatively truncated phospholipid, and [(3)H]PAF clearance was slowed in hyperlipidemic apolipoprotein (apo)E(-/-) mice with excess circulating oxidatively truncated phospholipids. [(3)H]PAF, fluorescent NBD-PAF, or fluorescent oxidatively truncated phospholipid were primarily accumulated by liver and lung, and were transported into endothelium as intact phospholipids through a common mechanism involving TMEM30a.Circulating PAF and oxidized phospholipids are continually and rapidly cleared, and hence continually and rapidly produced. Saturable PAF receptor-independent transport, rather than just intravascular hydrolysis, controls circulating inflammatory and proapoptotic oxidized phospholipid mediators. Intravascular PAF has access to intracellular compartments. Inflammatory and proapoptotic phospholipids may accumulate in the circulation as transport is overwhelmed by substrates in hyperlipidemia.
STUDIES ON HUMAN ANTIBODIES
Authors: G. M. Edelman, Elvin A. Kabat
Journal: The Journal of Experimental Medicine (1964)

Specific precipitates and purified human antibodies were reduced and alkylated and subjected to starch gel electrophoresis in 8 M urea to dissociate and separate the L and H polypeptide chains. Dissociated antibodies to dextran, levan, teichoic acid, blood group A substance, and tetanus toxoid showed sharp bands corresponding to L polypeptide chains. The patterns differed for antibodies of different specificities. Some differences were also seen among antibodies of the same specificity from different individuals. Purified antidextran antibodies showed particularly simple patterns resembling those of purified human gamma myeloma proteins. In some cases only one L chain band was present.
Cisplatin-Induced CD95 Redistribution into Membrane Lipid Rafts of HT29 Human Colon Cancer Cells
Authors: Sandrine Lacour, Arlette Hammann, Solène Grazide, Dominique Lagadic-Gossmann, Anne Athias, Odile Sergent, Guy Laurent, Philippe Gambert, Eric Solary, Marie-Thérèse Dimanche-Boitrel
Journal: Cancer Research (2004)

Abstract We have shown previously that the death receptor CD95 could contribute to anticancer drug-induced apoptosis of colon cancer cells. In addition, anticancer drugs cooperate with CD95 cognate ligand or agonistic antibodies to trigger cancer cell apoptosis. In the present study, we show that the anticancer drug cisplatin induces clustering of CD95 at the surface of the human colon cancer cell line HT29, an event inhibited by the inhibitor of acid sphingomyelinase (aSMase) imipramine. The cholesterol sequestering agent nystatin also prevents cisplatin-induced CD95 clustering and decreases HT29 cell sensitivity to cisplatin-induced apoptosis and the synergy between cisplatin and anti-CD95 agonistic antibodies. CD95, together with the adaptor molecule Fas-associated death domain and procaspase-8, is redistributed into cholesterol- and sphingolipid-enriched cell fractions after cisplatin treatment, suggesting plasma membrane raft involvement. Interestingly, nystatin prevents the translocation of the aSMase to the extracellular surface of plasma membrane and the production of ceramide, suggesting that these early events require raft integrity. In addition, nystatin prevents cisplatin-induced transient increase in plasma membrane fluidity that could be required for CD95 translocation. Together, these results demonstrate that cisplatin activates aSMase and induces ceramide production, which triggers the redistribution of CD95 into the plasma membrane rafts. Such redistribution contributes to cell death and sensitizes tumor cells to CD95-mediated apoptosis.
Guinea-pig tracheal responsiveness &lt;I&gt;in vitro&lt;/I&gt; following general anaesthesia with halothane
Authors: F.J. Mercier, A. Denjean
Journal: European Respiratory Journal (1996)

Halothane and isoflurane induce potent bronchodilation during general anaesthesia and have been used successfully during status asthmaticus. The aim of this study was to determine whether airway hyporesponsiveness was prolonged after halothane administration. Sixteen guinea-pigs were submitted for 2 h to either 1.5% halothane in oxygen or 100% oxygen, and were killed 24 h later to elicit isometric tracheal contractions in organ baths with various agonists. Cumulative concentration-response curves to histamine or to KCl and contractions evoked with acetylcholine 1 mM (4.7 +/- 0.8 vs 4.6 +/- 0.5 g) or carbachol 10 microM in calcium-free buffer (4.3 +/- 0.6 vs 4.4 +/- 0.6 g) exhibited no difference between groups. Moreover, when 4% halothane or 4.6% isoflurane were directly bubbled through the organ baths, a significant decrease (13 +/- 1% and 37 +/- 2%) of maximal contractions evoked with acetylcholine and KCI, respectively, was obtained but these relaxant effects did not persist 30 min after cessation of anaesthetic. These results indicate that, even though halothane induces transient airway hyporesponsiveness in vitro, previous halothane anaesthesia in guinea-pigs does not alter subsequent tracheal responsiveness assessed in vitro. Our findings may explain the transient renewal of bronchospasm reported during intermittent periods off halothane in status asthmaticus.
Expression of αvβ8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice
Authors: Andrew C. Melton, Samantha L. Bailey-Bucktrout, Mark A. Travis, Brian T. Fife, Jeffrey A. Bluestone, Dean Sheppard
Journal: Journal of Clinical Investigation (2010)

Th17 cells promote a variety of autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. TGF-β is required for conversion of naive T cells to Th17 cells, but the mechanisms regulating this process are unknown. Integrin αvβ8 on DCs can activate TGF-β, and this process contributes to the development of induced Tregs. Here, we have now shown that integrin αvβ8 expression on DCs plays a critical role in the differentiation of Th17 cells. Th17 cells were nearly absent in the colons of mice lacking αvβ8 expression on DCs. In addition, these mice and the DCs harvested from them had an impaired ability to convert naive T cells into Th17 cells in vivo and in vitro, respectively. Importantly, mice lacking αvβ8 on DCs showed near-complete protection from experimental autoimmune encephalomyelitis. Our results therefore suggest that the integrin αvβ8 pathway is biologically important and that αvβ8 expression on DCs could be a therapeutic target for the treatment of Th17-driven autoimmune disease.
Proteome and computational analyses reveal new insights into the mechanisms of hepatitis C virus-mediated liver disease posttransplantation
Authors: Deborah L. Diamond, Alexei L. Krasnoselsky, Kristin E. Burnum, Matthew E. Monroe, Bobbie-Jo Webb-Robertson, Jason E. McDermott, Matthew M. Yeh, Jose Felipe Golib Dzib, Nathan Susnow, Susan Strom, Sean C. Proll, Sarah E. Belisle, David E. Purdy, Angela L. Rasmussen, Kathie-Anne Walters, Jon M. Jacobs, Marina A. Gritsenko, David G. Camp, Renuka Bhattacharya, James D. Perkins, Robert L. Carithers, Iris W. Liou, Anne M. Larson, Arndt Benecke, Katrina M. Waters, Richard D. Smith, Michael G. Katze
Journal: Hepatology (2012)

Liver transplant tissues offer the unique opportunity to model the longitudinal protein abundance changes occurring during hepatitis C virus (HCV)-associated liver disease progression in vivo. In this study, our goal was to identify molecular signatures, and potential key regulatory proteins, representative of the processes influencing early progression to fibrosis. We performed global protein profiling analyses on 24 liver biopsy specimens obtained from 15 HCV(+) liver transplant recipients at 6 and/or 12 months posttransplantation. Differentially regulated proteins associated with early progression to fibrosis were identified by analysis of the area under the receiver operating characteristic curve. Analysis of serum metabolites was performed on samples obtained from an independent cohort of 60 HCV(+) liver transplant patients. Computational modeling approaches were applied to identify potential key regulatory proteins of liver fibrogenesis. Among 4,324 proteins identified, 250 exhibited significant differential regulation in patients with rapidly progressive fibrosis. Patients with rapid fibrosis progression exhibited enrichment in differentially regulated proteins associated with various immune, hepatoprotective, and fibrogenic processes. The observed increase in proinflammatory activity and impairment in antioxidant defenses suggests that patients who develop significant liver injury experience elevated oxidative stresses. This was supported by an independent study demonstrating the altered abundance of oxidative stress-associated serum metabolites in patients who develop severe liver injury. Computational modeling approaches further highlight a potentially important link between HCV-associated oxidative stress and epigenetic regulatory mechanisms impacting on liver fibrogenesis.Our proteome and metabolome analyses provide new insights into the role for increased oxidative stress in the rapid fibrosis progression observed in HCV(+) liver transplant recipients. These findings may prove useful in prognostic applications for predicting early progression to fibrosis.
Molecular basis for fibrinogen Dusart (A alpha 554 Arg--&gt;Cys) and its association with abnormal fibrin polymerization and thrombophilia.
Authors: J Koopman, F Haverkate, J Grimbergen, S T Lord, M W Mosesson, J P DiOrio, K S Siebenlist, C Legrand, J Soria, C Soria
Journal: Journal of Clinical Investigation (1993)

The molecular defect in the abnormal fibrinogen Dusart (Paris V) that is associated with thrombophilia was determined by sequence analysis of genomic DNA that had been amplified using the polymerase chain reaction. The propositus was heterozygous for a single base change (C-->T) in the A alpha-chain gene, resulting in the amino acid substitution A alpha 554 Arg-->Cys. Restriction analysis of the amplified DNA derived from the family members showed that his father and his two sons were also heterozygous. Electron microscopic studies on fibrin formed from purified fibrinogen Dusart demonstrated fibers that were much thinner than in normal fibrin. In contrast to the previously observed defective binding of plasminogen, the binding of thrombospondin to immobilized fibrinogen Dusart was similar to that of normal fibrinogen. Immunoblot analysis of plasma fibrinogen demonstrated that a substantial part of the fibrinogen Dusart molecules were disulfide-linked to albumin. The plasma of the affected family members also contained fibrinogen-albumin complexes. Furthermore, small amounts of high molecular weight complexes containing fibrinogen were detected in all the heterozygous individuals. These data indicate that the molecular abnormality in fibrinogen Dusart (A alpha 554 Arg-->Cys) results in defective lateral association of the fibrin fibers and disulfide-linked complex formation with albumin, and is associated with a family history of recurrent thrombosis in the affected individuals.
Massive Gastrointestinal Bleeding Due to an Aorto-enteric Fistula Seen by Technetium-99m-Labeled Red Blood Cell Scintigraphy
Authors: Perry S Gerard, Paul Z Gerczuk, Raghu Idupuganti, Madhavi Patnana
Journal: Clinical Nuclear Medicine (2007)

A 40-year-old male patient presented to the emergency room complaining of fatigue, weakness, and decreased appetite for the last 2–3 weeks. The patient had a history of bladder cancer and a congenital abnormality of the genitourinary tract, the details of which were unclear. On physical examination, he was found to be hypotensive and tachycardic with guaiac positive stool. The patient's hematocrit was rapidly falling and technetium-99m-labeled red blood cell (Tc-99m-RBC) scintigraphy was performed to localize the site of bleeding.
Hyperventilation with Cold versus Dry Air in 2- to 5-Year-Old Children with Asthma
Authors: Kim G. Nielsen, Hans Bisgaard
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Cold air challenge (CACh) has been shown to discriminate between children with asthma and healthy young children. Hyperventilation with dry room-temperature air is a simplified alternative. We compared responsiveness in young children with asthma between two standardized, single-step protocols: dry air challenge (DACh) performed as 6 minutes of eucapnic hyperventilation with dry room-temperature air and CACh as 4 minutes of hyperventilation. Response was measured as specific airway resistance by whole-body plethysmography and expressed as change from baseline in numbers of within-subject SDs (SDw). The challenge sequence was randomly assigned. A comparator challenge was performed 1 hour later if the first challenge gave a change of 3 SDw or more. Forty 2- to 5-year-old children with asthma were included. Responsiveness to cold versus dry air showed significant, but weak, correlation (r(2) = 0.34, p < 0.0001), but responsiveness to CACh exceeded DACh (7.6 vs. 5.4 SDw, p < 0.02). CACh seemed to induce reduction in response to the following DACh (p < 0.01), whereas no such reduction was seen after DACh.Responsiveness to CACh exceeded responsiveness to DACh, and CACh seemed to induce refractoriness in contrast to DACh, probably because of the additional stimulus from airway cooling. This finding suggests CACh as the preferred method of challenge.
DRUG-ELUTING STENTS FOR THE TREATMENT OF LEFT MAIN CORONARY ARTERY DISEASE WITH SIROLIMUS, PACLITAXEL, ZOTAROLIMUS, BIOLIMUSA9, EPC CAPTURE AND EVEROLIMUS-ELUTING STENT: MULTICENTER REGISTRY IN ASIA
Authors: Sunao Nakamura, Shotaro Nakamura, Hisao Ogawa, Jang-Ho Bae, Yeo Hans Cahyadi, Wasan Udayachalerm, Damras Tresukosol, Sudaratana Tansuphaswadikul
Journal: Journal of the American College of Cardiology (2010)
Depression of Contractile Force of Skeletal Muscle by Intra-arterial Vasodilator Drugs
Authors: LEO HIRVONEN, MELVIN KOROBKIN, RALPH R. SONNENSCHEIN, DAVID L. WRIGHT
Journal: Circulation Research (1964)

The intra-arterial administration of vasodilator drugs (acetylcholine, histamine, isoproterenol, adenosine triphosphate, bradykinin, and isoxsuprine hydrochloride) induced reversible depression in the maximal contractile force of the intermittently stimulated gastrocnemius-soleus muscles in the cat. In general, blood flow to the muscles was held constant and perfusion pressure was observed. The agents were effective in depressing the muscle at doses the same as those required to produce dilatation in the resting muscle. Increase in blood flow during infusion could reverse the depression. Atropine, in amounts sufficient to block the hypotensive action of intravenously administered acetylcholine, prevented the muscle depressant action of the latter, while leaving unaffected the action of histamine. Further experiments, utilizing mainly acetylcholine as the prototype, were performed to test the hypothesis that the depressant effect on the gastrocnemius was closely related to a vascular action of the drugs. Evidence serving both to exclude neuromuscular blockade and to support a vascular effect was adduced from three sets of observations. 1) In vitro tests of blocking action of acetylcholine and histamine on nerve-muscle preparations indicated that any such action would require doses several hundred times greater than those effective in the cat gastrocnemius. 2) Under conditions where dependency of contractile force on blood flow varied, comparison of the effects of acetylcholine to d -tubocurarine and decamethonium on the cat gastrocnemius showed that when dependency on flow was reduced the effect of acetylcholine was also, while neuromuscular blockade was affected little. 3) A decrease occurred in the I 131 clearance rate from the gastrocnemius parallel to the reduction in muscle force from acetylcholine, while a much smaller, or delayed, reduction in rate occurred when force was reduced equally by d -tuboeurarine. A redistribution of blood flow within the muscle and associated connective tissue may account for the results.
Isolation of type-specific polysaccharide antigen from group B type Ib streptococci.
Authors: J Y Tai, E C Gotschlich, R C Lancefield
Journal: The Journal of Experimental Medicine (1979)

Group B streptococcus type Ib (strain H36B) was subjected to digestion with extracellular muralytic enzymes prepared from Streptomyces albus. Type Ib-specific polysaccharide antigen was isolated from the lysate by alcohol precipitation and Sepharose 6B chromatography. The purified type Ib antigen has a Kd value of 0.31 on a Sepharose 4B column and contains four sugars, galactose, glucose, N-acetyl glucosamine, and sialic acid in a molar ratio of 2.05:0.86:1.00:0.90. Acid treatment (pH 2.0) of this polysaccharide results in partial degradation of the antigen (Kd = 0.41 on Sepharose 4B) with the loss of 93% of the sialic acid. The molar ratio of the remaining sugars in the polysaccharide remains identical to that in the native one. This suggests that the sialic acid is at the terminal position in the molecule. Both intact and acid-treated antigen cross-react with some type Ia and type Ic antisera as a result of the common Iabc determinant, but not with type II and type III antisera. Absorption studies indicate that Ib-specific determinant and Iabc determinant are on the same molecule and that sialic acid is not the cross-reactive determinant.
Functional Inactivation in the Whole Population of Human Vγ9/Vδ2 T Lymphocytes Induced By a Nonpeptidic Antagonist
Authors: Martin R. Bürk, Ilaria Carena, Alena Donda, Francesca Mariani, Lucia Mori, Gennaro De Libero
Journal: The Journal of Experimental Medicine (1997)

Nonpeptidic compounds stimulate human T cells bearing the TCR-γδ in the absence of major histocompatibility complex restriction. We report that one of these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of Vγ9/Vδ T cells ex vivo, antagonizes the same cell population after repetitive activation. Stimulation with DPG results in partial early protein tyrosine phosphorylation and a prolonged, but reversible, state of unresponsiveness to agonist ligands in Vγ9/Vδ2, but not in other T cells. These findings show that TCR antagonism is a general phenomenon of T cells. However, in contrast to the clonal specificity of altered peptides antagonizing αβ T cells, all the tested Vγ9/Vδ2 polyclonal cell lines and clones become unresponsive, a fact that may be relevant for the regulation of their response in vivo.
The water resistance of sunscreen and day-care products
Authors: None STOKES, None DIFFEY
Journal: British Journal of Dermatology (1999)

The water resistance of 10 sunscreen products and three day-care products containing ultraviolet filters has been assessed using an in vitro method based on transmission spectrometry. The sunscreen products which claimed to be ‘water resistant’ or ‘waterproof’ had significantly better substantivity than products which made no claim concerning water resistance. However, there was no significant difference between the substantivities of the ‘water resistant’ and ‘waterproof’ products, suggesting that it may be unnecessary to differentiate between these two categories on product labelling. Consumers would find choosing a sunscreen product more straightforward if sunscreens were simply labelled either ‘water resistant’ or ‘not water resistant’. The day-care products were readily washed off, losing almost all photoprotection after one 20-min immersion. The water resistance of four products was measured using water temperatures of 20°, 25° and 30 °C. In three products water temperature had no effect on substantivity, although one product washed off more readily with increasing temperature.
Can Admission and Fasting Glucose Reliably Identify Undiagnosed Diabetes in Patients With Acute Coronary Syndrome?
Authors: Onyebuchi E. Okosieme, Rajesh Peter, Muhammad Usman, Hemanth Bolusani, Prem Suruliram, Lindsay George, L. Marc Evans
Journal: Diabetes Care (2008)

Our objectives were to determine the prevalence of previously undiagnosed abnormal glucose tolerance, i.e., diabetes and impaired glucose tolerance (IGT) in patients with acute coronary syndrome and to assess the utility of admission and fasting glucose in identifying diabetes in these patients.Glycemic status was characterized on the basis of admission plasma glucose (APG), fasting plasma glucose (FPG), and an oral glucose tolerance test (OGTT) in 140 patients admitted to the hospital with acute coronary syndrome, who were not known to have diabetes (mean +/- SD age 67.3 +/- 13.4 years; 79% men). OGTTs were performed on days 5-7 after admission.The prevalences of diabetes and IGT were 27 and 39%, respectively, according to OGTT criteria. Receiver operating characteristic curves showed that the area under the curve for diagnosing diabetes was 0.83 (P < 0.001) for FPG, 0.79 (P < 0.001) for APG, and 0.84 (P < 0.001) for FPG and APG applied in combination. A FPG cutoff >or=5.6 mmol/l (100 mg/dl) and/or APG >or=7.8 mmol/l (140 mg/dl) yielded a sensitivity of 89.5% and a positive predictive value of 43.6% for detecting diabetes.A high prevalence of abnormal glucose tolerance was seen in patients with acute coronary syndrome. The combination of FPG >or=5.6 mmol/l (100 mg/dl) and/or APG >or=7.8 mmol/l (140 mg/dl) was highly sensitive for identifying diabetes. Although weakly specific, this simple algorithm could offer a practical initial screening tool at the acute setting in the high-risk population with acute coronary syndrome.