The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Nathan Brinkman - One of the best experts on this subject based on the ideXlab platform.
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haptoglobin and hemopexin inhibit vaso occlusion and inflammation in murine sickle cell disease role of heme oxygenase 1 induction
PLOS ONE, 2018Co-Authors: John D Belcher, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Hao Nguyen, Phong Nguyen, Trevor Killeen, Sylvia Miescher, Nathan BrinkmanAbstract:During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. Plasma haptoglobin and hemopexin scavenge free hemoglobin and heme, respectively, but can be depleted in hemolytic states. Haptoglobin and hemopexin supplementation protect tissues, including the vasculature, liver and kidneys. It is widely assumed that these protective effects are due primarily to hemoglobin and heme clearance from the vasculature. However, this simple assumption does not account for the consequent cytoprotective adaptation seen in cells and organs. To further address the mechanism, we used a hyperhemolytic murine model (Townes-SS) of sickle cell disease to examine cellular responses to haptoglobin and hemopexin supplementation. A single infusion of haptoglobin or hemopexin (± equimolar hemoglobin) in SS-mice increased heme oxygenase-1 (HO-1) in the liver, kidney and skin several fold within 1 hour and decreased nuclear NF-ĸB phospho-p65, and vaso-occlusion for 48 hours after infusion. Plasma hemoglobin and heme levels were not significantly changed 1 hour after infusion of haptoglobin or hemopexin. Haptoglobin and hemopexin also inhibited hypoxia/reoxygenation and lipopolysaccharide-induced vaso-occlusion in SS-mice. Inhibition of HO-1 activity with tin protoporphyrin blocked the protections afforded by haptoglobin and hemopexin in SS-mice. The HO-1 reaction product carbon monoxide, fully restored the protection, in part by inhibiting Weibel-Palade body mobilization of P-selectin and von Willebrand factor to endothelial cell surfaces. Thus, the mechanism by which haptoglobin and hemopexin supplementation in hyperhemolytic SS-mice induces cytoprotective cellular responses is linked to increased HO-1 activity.
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haptoglobin and hemopexin infusion efficiently activates the nrf2 ho 1 axis and inhibits inflammation and vaso occlusion in murine sickle cell disease
Blood, 2016Co-Authors: John D Belcher, Nathan Brinkman, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Hao Nguyen, Phong Nguyen, Gregory M VercellottiAbstract:Free hemoglobin and hemin, released by red blood cells during intravascular hemolysis, promote vasculopathy, inflammation, thrombosis, and renal injury. Plasma haptoglobin and hemopexin tightly bind free hemoglobin and hemin, respectively, thwarting these clinical sequelae. In sickle cell disease (SCD), chronic hemolysis can deplete plasma haptoglobin and hemopexin in humans and mice. To explore mechanisms mediating this protection and provide a basis for supplementation in SCD patients, dorsal skin fold chambers were implanted onto Townes-SS mice and microvascular stasis (% non-flowing venules) was measured in response to a hemoglobin challenge. Human haptoglobin, hemopexin, or albumin was co-infused with hemoglobin or 1 hour after hemoglobin at equimolar concentrations. Sickle mice co-infused with hemoglobin/haptoglobin, hemoglobin/hemopexin or hemoglobin/haptoglobin/hemopexin had less stasis 1 to 4 hours after infusion, compared to albumin- and saline-treated mice (*p Disclosures Belcher:CSL-Behring: Research Funding; Imara: Research Funding. Chen:Imara: Research Funding. Brinkman:CSL-Behring: Employment. Vercellotti:CSL-Behring: Research Funding; Imara: Research Funding.
P D Eckersall - One of the best experts on this subject based on the ideXlab platform.
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blood serum acute phase proteins and iron dynamics during acute phase response of salmonella enterica serotype dublin experimentally infected buffalo calves
Veterinary Immunology and Immunopathology, 2018Co-Authors: A M Santana, P D Eckersall, Daniela Gomes Da Silva, F C Thomas, P A Bernardes, Lucas Jose Luduverio Pizauro, Clarissa Helena Santana, Richard Burchmore, J J FagliariAbstract:Abstract The study aimed to evaluate clinical signs, blood serum acute phase proteins (APP) and iron dynamics during the acute phase response (APR) of Salmonella Dublin experimentally infected Murrah buffalo calves. Six buffalo calves constituted the control group (CNT) and six were orally inoculate with 108 CFU of S. Dublin (INF). Clinical evaluation was performed, rectal swabs to detect S. Dublin strains were collected and venous blood was sampled before and throughout seven days after inoculation. The APP fractions β-haptoglobin, α-haptoglobin, ceruloplasmin and transferrin were analyzed by 1-D and 2-D electrophoresis. Proteins were identified using LC/ESI-MS/MS and NCBI database. Plasma fibrinogen, serum iron and serum haptoglobin concentrations were measured. The inoculation of 108 CFU of S. Dublin was effective in inducing clinical signs of Salmonellosis, such as hyperthermia and diarrhea. 1-DE showed that β and α-haptoglobin increased 204% (p = 0.008) and 184% (p = 0.022) 48 h after inoculation (HAI), respectively, with highest concentrations 120 HAI (498% increased, p = 0.012; 431% increased, p = 0.011) and 168 HAI (492% increased, p = 0.019; 523% increased, p = 0.028). 2-DE showed that the expression of two spots, identified as β-haptoglobin, were increased 693% (p = 0.0006) and 580% (p = 0.0003) 168 HAI, respectively, while one spot, identified as α-haptoglobin, increased 714% (p = 0.040). Haptoglobin concentrations increased 1339% (p
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influence of rearing conditions and respiratory disease on haptoglobin levels in the pig at slaughter
Research in Veterinary Science, 2007Co-Authors: J R Amory, P D Eckersall, A M Mackenzie, M J Stear, G P PearceAbstract:Associations between serum concentrations of haptoglobin, pathological lung lesions indicative of Mycoplasma hyopneumoniae (EP) or Actinobacillus pleuropneumoniae (PL) infection at slaughter and previous rearing environment were investigated in 510 pigs (90–100 kg live weight) from 17 farms in England. Haptoglobin concentrations were significantly higher in pigs showing pathological signs of EP infection compared to those without signs of this disease (EP positive median 0.43 mg ml 1 vs. EP negative median 0.26 mg ml 1 , p < 0.01). However, there were no significant associations between serum haptoglobin concentrations and pathological signs of PL. The presence of solid partitions compared with barred or similar open partitions was associated with a decrease of 0.44 mg ml 1 farm mean haptoglobin concentration, whilst an increase in pen size of 10 m 2 was associated with a decrease of 0.08 mg ml 1 farm mean haptoglobin concentration. The findings indicate that pathological signs of EP were associated with increased serum haptoglobin at slaughter, which in turn was influenced by components of the farm environment. 2007 Elsevier Ltd. All rights reserved.
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haptoglobin and serum amyloid a in milk and serum during acute and chronic experimentally induced staphylococcus aureus mastitis
Journal of Dairy Research, 2003Co-Authors: Ulrika Gronlund, Cecilia Hulten, P D Eckersall, C J Hogarth, Karin Persson WallerAbstract:Local and systemic changes in the acute phase proteins, haptoglobin and serum amyloid A (SAA), were studied in six dairy cows during the acute and chronic phases of experimentally induced Staphylococcus aureus mastitis. Haptoglobin and SAA were measured in serum, and in milk from infected and healthy control udder quarters within each cow. Concentrations of haptoglobin and SAA increased rapidly in both serum and milk during the acute phase of mastitis and followed a similar pattern. Significantly raised milk concentrations of SAA were also found during chronic subclinical mastitis. Serum concentrations of SAA also tended to be higher during the chronic phase than pre-infection. Increases in milk haptoglobin and SAA were specific for the infected udder quarters. In conclusion, measurement of SAA in milk samples could be a useful tool in diagnosing mastitis.
John D Belcher - One of the best experts on this subject based on the ideXlab platform.
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haptoglobin and hemopexin inhibit vaso occlusion and inflammation in murine sickle cell disease role of heme oxygenase 1 induction
PLOS ONE, 2018Co-Authors: John D Belcher, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Hao Nguyen, Phong Nguyen, Trevor Killeen, Sylvia Miescher, Nathan BrinkmanAbstract:During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. Plasma haptoglobin and hemopexin scavenge free hemoglobin and heme, respectively, but can be depleted in hemolytic states. Haptoglobin and hemopexin supplementation protect tissues, including the vasculature, liver and kidneys. It is widely assumed that these protective effects are due primarily to hemoglobin and heme clearance from the vasculature. However, this simple assumption does not account for the consequent cytoprotective adaptation seen in cells and organs. To further address the mechanism, we used a hyperhemolytic murine model (Townes-SS) of sickle cell disease to examine cellular responses to haptoglobin and hemopexin supplementation. A single infusion of haptoglobin or hemopexin (± equimolar hemoglobin) in SS-mice increased heme oxygenase-1 (HO-1) in the liver, kidney and skin several fold within 1 hour and decreased nuclear NF-ĸB phospho-p65, and vaso-occlusion for 48 hours after infusion. Plasma hemoglobin and heme levels were not significantly changed 1 hour after infusion of haptoglobin or hemopexin. Haptoglobin and hemopexin also inhibited hypoxia/reoxygenation and lipopolysaccharide-induced vaso-occlusion in SS-mice. Inhibition of HO-1 activity with tin protoporphyrin blocked the protections afforded by haptoglobin and hemopexin in SS-mice. The HO-1 reaction product carbon monoxide, fully restored the protection, in part by inhibiting Weibel-Palade body mobilization of P-selectin and von Willebrand factor to endothelial cell surfaces. Thus, the mechanism by which haptoglobin and hemopexin supplementation in hyperhemolytic SS-mice induces cytoprotective cellular responses is linked to increased HO-1 activity.
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haptoglobin and hemopexin infusion efficiently activates the nrf2 ho 1 axis and inhibits inflammation and vaso occlusion in murine sickle cell disease
Blood, 2016Co-Authors: John D Belcher, Nathan Brinkman, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Hao Nguyen, Phong Nguyen, Gregory M VercellottiAbstract:Free hemoglobin and hemin, released by red blood cells during intravascular hemolysis, promote vasculopathy, inflammation, thrombosis, and renal injury. Plasma haptoglobin and hemopexin tightly bind free hemoglobin and hemin, respectively, thwarting these clinical sequelae. In sickle cell disease (SCD), chronic hemolysis can deplete plasma haptoglobin and hemopexin in humans and mice. To explore mechanisms mediating this protection and provide a basis for supplementation in SCD patients, dorsal skin fold chambers were implanted onto Townes-SS mice and microvascular stasis (% non-flowing venules) was measured in response to a hemoglobin challenge. Human haptoglobin, hemopexin, or albumin was co-infused with hemoglobin or 1 hour after hemoglobin at equimolar concentrations. Sickle mice co-infused with hemoglobin/haptoglobin, hemoglobin/hemopexin or hemoglobin/haptoglobin/hemopexin had less stasis 1 to 4 hours after infusion, compared to albumin- and saline-treated mice (*p Disclosures Belcher:CSL-Behring: Research Funding; Imara: Research Funding. Chen:Imara: Research Funding. Brinkman:CSL-Behring: Employment. Vercellotti:CSL-Behring: Research Funding; Imara: Research Funding.
Karin Persson Waller - One of the best experts on this subject based on the ideXlab platform.
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haptoglobin and serum amyloid a in milk from dairy cows with chronic sub clinical mastitis
Veterinary Research, 2005Co-Authors: Ulrika Gronlund, Karin Persson Waller, Charlotte Hallen SandgrenAbstract:New tools are needed to detect chronic sub-clinical mastitis, especially in automatic milking systems. Haptoglobin and serum amyloid A (SAA) are the two most sensitive bovine acute phase proteins, and their concentrations increase in milk from cows with clinical mastitis and in milk from cows with experimentally induced chronic sub-clinical Staphylococcus aureus mastitis. The aim of this study was to further evaluate the potential for haptoglobin and SAA in milk as indicators of chronic sub-clinical mastitis. Quarter milk samples were collected from 41 cows with a mean composite milk somatic cell count (CSCC) above 300,000 cells/mL during at least two months prior to sampling. Quarter milk samples were also taken from eleven cows with a mean CSCC below 80,000 cells/mL during at least two previous months. These samples were analysed for haptoglobin, SAA, adenosine triphosphate (ATP) activity and bacterial growth. The samples were grouped according to their ATP, haptoglobin and SAA status. ATP+ samples had ATP > 2 x 10(-10) mol/mL, Hp+ and SAA+ samples had detectable levels of haptoglobin (> or = 0.3 mg/L) and SAA (> or = 0.9 mg/L), respectively. In udder quarter samples from healthy cows, 42 out of 44 samples belonged to the ATP-Hp-SAA- group. Among cows with chronic sub-clinical mastitis, the ATP+Hp+SAA+ group contained 66 out of 164 samples while 44 samples belonged to the ATP+Hp-SAA- group. Detectable levels of haptoglobin and SAA were found in 92 and 80 samples, respectively. Growth of udder pathogens was detected in 28 samples and Staphylococcus aureus was the most common bacteria. In conclusion, haptoglobin and SAA concentrations below the detection limit were considered as good indicators of healthy udder quarters. A substantial variation in haptoglobin and SAA concentrations in milk was observed in udder quarters with chronic sub-clinical mastitis.
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haptoglobin and serum amyloid a in milk and serum during acute and chronic experimentally induced staphylococcus aureus mastitis
Journal of Dairy Research, 2003Co-Authors: Ulrika Gronlund, Cecilia Hulten, P D Eckersall, C J Hogarth, Karin Persson WallerAbstract:Local and systemic changes in the acute phase proteins, haptoglobin and serum amyloid A (SAA), were studied in six dairy cows during the acute and chronic phases of experimentally induced Staphylococcus aureus mastitis. Haptoglobin and SAA were measured in serum, and in milk from infected and healthy control udder quarters within each cow. Concentrations of haptoglobin and SAA increased rapidly in both serum and milk during the acute phase of mastitis and followed a similar pattern. Significantly raised milk concentrations of SAA were also found during chronic subclinical mastitis. Serum concentrations of SAA also tended to be higher during the chronic phase than pre-infection. Increases in milk haptoglobin and SAA were specific for the infected udder quarters. In conclusion, measurement of SAA in milk samples could be a useful tool in diagnosing mastitis.
Eiji Miyoshi - One of the best experts on this subject based on the ideXlab platform.
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identification of an inducible factor secreted by pancreatic cancer cell lines that stimulates the production of fucosylated haptoglobin in hepatoma cells
Biochemical and Biophysical Research Communications, 2008Co-Authors: Megumi Narisada, Tsutomu Nakagawa, Kenta Moriwaki, Sayuri Kawamoto, Kana Kuwamoto, Hitoshi Matsumoto, Michio Asahi, Nobuto Koyama, Eiji MiyoshiAbstract:Summary Fucosylation is one of the most important oligosaccharide modifications and is involved in cancer and inflammation. Recently, fucosylated haptoglobin was identified as a possible tumor marker for pancreatic cancer. The molecular mechanism underlying increases in fucosylated haptoglobin in sera of patients with pancreatic cancer seems to be complicated. Our previous study [N. Okuyama, Y. Ide, M. Nakano, T. Nakagawa, K. Yamanaka, K. Moriwaki, K. Murata, H. Ohigashi, S. Yokoyama, H. Eguchi, O. Ishikawa, T. Ito, M. Kato, A. Kasahara, S. Kawano, J. Gu, N. Taniguchi, E. Miyoshi, Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation, Int. J. Cancer 118 (11) (2006) 2803–2808] demonstrated that pancreatic cancer cells secrete a factor, which induces the production of haptoglobin in hepatoma cells. In the present study, we found that interleukin 6 (IL6) expressed in pancreatic cancer is a factor that induces the haptoglobin production, using a neutralizing antibody for IL6. Real-time PCR analyses revealed the up-regulation of fucosylation regulatory genes after IL6 treatment, resulting increases in fucosylated haptoglobin being revealed by a lectin ELISA. This pathway could be one of the possible mechanisms underlying increases in haptoglobin in sera of patients with pancreatic cancer.
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site specific analysis of n glycans on haptoglobin in sera of patients with pancreatic cancer a novel approach for the development of tumor markers
International Journal of Cancer, 2008Co-Authors: Miyako Nakano, Tsutomu Nakagawa, Toshifumi Ito, Takatoshi Kitada, Taizo Hijioka, Akinori Kasahara, Michiko Tajiri, Yoshinao Wada, Naoyuki Taniguchi, Eiji MiyoshiAbstract:It was found in our previous studies that the concentration of fucosylated haptoglobin had increased in the sera of patients with pancreatic cancer (PC) compared to those of other types of cancer and normal controls. Haptoglobin, an acute phase protein, has four potential N-glycosylation sites, although it remains unknown which site is responsible for the change in fucosylated N-glycans. In the present study, site-specific N-glycan structures of haptoglobin in sera obtained from patients with PC or chronic pancreatitis (CP) were analyzed using liquid chromatography-electrospray ionization mass spectrometry. Mass spectrometry analyses demonstrated that concentrations of total fucosylated di-, tri- and tetra-branched glycans of haptoglobin increased in the sera of PC patients. Tri-antennary N-glycans containing a Lewis X-type fucose markedly increased at the Asn211 site of haptoglobin N-glycans. While fucosylated N-glycans derived from serum haptoglobin of patients with CP slightly increased, di-fucosylated tetra-antennary N-glycans were observed only at this site in PC patients, and were absent in the haptoglobin of normal controls and individuals with CP. Thus, the present study provides evidence that site-specific analyses of N-glycans may be useful as novel tumor markers for PC.
