Science.gov

Sample records for acute-phase proteins app

  1. Avian acute phase protein ovotransferrin modulates phagocyte function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute phase proteins (APP) are serum proteins elevated in response to a variety of physiological injuries including infection and inflammation. These pathogen nonspecific proteins are predominantly synthesized in the liver and serve as a humoral component of innate immunity by way of recognizing and...

  2. Early post parturient changes in milk acute phase proteins.

    PubMed

    Thomas, Funmilola C; Waterston, Mary; Hastie, Peter; Haining, Hayley; Eckersall, P David

    2016-08-01

    The periparturient period is one of the most critical periods in the productive life of a dairy cow, and is the period when dairy cows are most susceptible to developing new intramammary infections (IMI) leading to mastitis. Acute phase proteins (APP) such as haptoglobin (Hp), mammary associated serum amyloid A3 (M-SAA3) and C-reactive protein (CRP) have been detected in milk during mastitis but their presence in colostrum and milk in the immediate postpartum period has had limited investigation. The hypothesis was tested that APP are a constituent of colostrum and milk during this period. Enzyme linked immunosorbent assays (ELISAs) were used to determine each APP's concentration in colostrum and milk collected daily from the first to tenth day following calving in 22 Holstein-Friesian dairy cows. Haptoglobin was assessed in individual quarters and composite milk samples while M-SAA3 and CRP concentration were determined in composite milk samples. Change in Hp in relation to the high abundance proteins during the transition from colostrum to milk were evaluated by 1 and 2 dimension electrophoresis and western blot. In 80% of the cows all APPs were detected in colostrum on the first day following parturition at moderately high levels but gradually decreased to minimal values in the milk by the 6th day after calving. The remaining cows (20%) showed different patterns in the daily milk APP concentrations and when an elevated level is detected could reflect the presence of IMI. Demonstration that APP are present in colostrum and milk following parturition but fall to low levels within 4 days means that elevated APP after this time could be biomarkers of post parturient mastitis allowing early intervention to reduce disease on dairy farms. PMID:27600971

  3. Acute Phase Proteins and Their Role in Periodontitis: A Review

    PubMed Central

    Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-01-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

  4. Acute Phase Proteins and Their Role in Periodontitis: A Review.

    PubMed

    Polepalle, Tejaswin; Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-11-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis.

  5. Acute phase proteins response to feed deprivation in broiler chickens.

    PubMed

    Najafi, P; Zulkifli, I; Soleimani, A F; Goh, Y M

    2016-04-01

    Feed deprivation in poultry farming imposes some degree of stress to the birds, and adversely affects their well -being. Serum levels of acute phase proteins (APP) are potential physiological indicators of stress attributed to feed deprivation. However, it has not been determined how long it takes for a measurable APP response to stressors to occur in avian species. An experiment was designed to delineate the APP and circulating levels of corticosterone responses in commercial broiler chickens to feed deprivation for 30 h. It was hypothesized that feed deprivation would elicit both APP and corticosterone (CORT) reactions within 30 h that is probably associated with stress of hunger. Twenty-one day old birds were subjected to one of 5 feed deprivation periods: 0 (ad libitum, AL), 6, 12, 18, 24, and 30 h. Upon completion of the deprivation period, blood samples were collected to determine serum CORT, ovotransferrin (OVT), α1-acid glycoprotein (AGP), and ceruloplasmin (CP) concentrations. Results showed that feed deprivation for 24 h or more caused a marked elevation in CORT (P=0.002 and P<0.0001, respectively) when compared to AL. However, increases in AGP (P=0.0005), CP (P=0.0002), and OVT (P=0.0003) were only noted following 30 h of feed deprivation. It is concluded that elicitation of AGP, CP, and OVT response may represent a more chronic stressful condition than CORT response in assessing the well-being of broiler chickens.

  6. The onset of the progression of acute phase response mechanisms induced by extreme impacts can be followed by the decrease in blood levels of positive acute phase proteins.

    NASA Astrophysics Data System (ADS)

    Larina, Olga; Bekker, Anna

    Studies performed at space flights and earth-based simulation models detected the plasma indices of acute phase reaction (APR), i.e. the increase of APR cytokine mediators and alterations in the production of blood acute phase proteins (APP) at the initial stages of adaptation to altered gravity conditions. Acute phase response is the principal constituent of the functional activity of innate immunity system. Changes in plasma APPs contents are considered to serve the restoration of homeostasis state. According to trends of their concentration shifts at the evolving of acute phase reaction APPs are denoted as positive, neutral, or negative. Plasma concentrations of positive acute phase proteins α1-acid glycoprotein (α1-AGP), α1-antitrypsin (α1-AT), and neutral α2-macroglobulin (α2-M) were measured in human study at 12-hour antiorthostatic position (AOP) with 15° head down tilt and hypoxia experiments at 14% oxygen in pressure chamber. Both of these impacts were shown to produce alterations in the APP levels indicative for acute phase response. Nevertheless, in AOP experiment noticeable decrease in α1-AGP concentration occurred by hour 12, and even more pronounced decline of α1-AGP and α1-AT were found on hypoxia hours 12 and 36. Acute phase proteins α1-AGP and α2-M possess the features of proteinase inhibitors. This function is implemented by the formation of complexes with the molecules of proteolytic enzymes which subsequently are removed from the blood flow. Transient decrease in plasma concentrations of protease inhibitors on early phases of APR development was reported to result from the growth of plasma protease activity due to cathepsin release from activated leukocytes, which had not yet been compensated by enhanced APP synthesis. Being a carrier protein for positively charged and neutral substances, α1-AGP shows pronounced elevation in its blood content during APR development. As assumed, it is required for the transportation of the increased

  7. Reference intervals for acute phase protein and serum protein electrophoresis values in captive Asian elephants (Elephas maximus).

    PubMed

    Isaza, Ramiro; Wiedner, Ellen; Hiser, Sarah; Cray, Carolyn

    2014-09-01

    Acute phase protein (APP) immunoassays and serum protein electrophoresis (SPEP) are assays for evaluating the inflammatory response and have use as diagnostic tools in a variety of species. Acute phase proteins are markers of inflammation that are highly conserved across different species while SPEP separates and quantifies serum protein fractions based on their physical properties. In the current study, serum samples from 35 clinically healthy Asian elephants (Elephas maximus) were analyzed using automated assays for C-reactive protein, serum amyloid A, and haptoglobin and SPEP. Robust methods were used to generate reference intervals for the APPs: C-reactive protein (1.3-12.8 mg/l), serum amyloid A (0-47.5 mg/l), and haptoglobin (0-1.10 mg/ml). In addition, SPEP was performed on these samples to establish reference intervals for each protein fraction. A combination of APPs and SPEP measurements are valuable adjunctive diagnostic tools in elephant health care.

  8. Reference intervals for acute phase protein and serum protein electrophoresis values in captive Asian elephants (Elephas maximus).

    PubMed

    Isaza, Ramiro; Wiedner, Ellen; Hiser, Sarah; Cray, Carolyn

    2014-09-01

    Acute phase protein (APP) immunoassays and serum protein electrophoresis (SPEP) are assays for evaluating the inflammatory response and have use as diagnostic tools in a variety of species. Acute phase proteins are markers of inflammation that are highly conserved across different species while SPEP separates and quantifies serum protein fractions based on their physical properties. In the current study, serum samples from 35 clinically healthy Asian elephants (Elephas maximus) were analyzed using automated assays for C-reactive protein, serum amyloid A, and haptoglobin and SPEP. Robust methods were used to generate reference intervals for the APPs: C-reactive protein (1.3-12.8 mg/l), serum amyloid A (0-47.5 mg/l), and haptoglobin (0-1.10 mg/ml). In addition, SPEP was performed on these samples to establish reference intervals for each protein fraction. A combination of APPs and SPEP measurements are valuable adjunctive diagnostic tools in elephant health care. PMID:25057161

  9. Acute Phase Responses to Novel, Investigational Vaccines in Toxicology Studies: The Relationship Between C-Reactive Protein and Other Acute Phase Proteins.

    PubMed

    Green, Martin D

    2015-01-01

    The objective of this study was to determine the effects of investigational vaccine candidates on acute-phase proteins (APPs) as determined in GLP toxicology studies. Sixty-four GLP toxicity studies, which were submitted to the Food and Drug Administration from 2008 to 2012 in support of proposed clinical investigations, were reviewed and entered into a database. These studies employed the intramuscular route of injection and were conducted using New Zealand White rabbits. A retrospective review of these GLP toxicity studies was conducted to evaluate the changes in plasma levels of C-reactive protein (CRP), fibrinogen, and albumin as APPs following the administration of various investigational vaccines. The incidence and intensity of responses associated with acute-phase responses both positive and negative were observed to increase in animals when treated with vaccines containing more potent immunological components such as novel adjuvants that activate Toll-like receptors in the investigational vaccine products. Changes in plasma levels of CRP were prominent among these responses and provided a basis to propose a classification scheme of H, M, L, and N responding groups. These changes in plasma proteins reflect an activation of the acute-phase response and indicate increasing levels of systemic inflammation, which potentially may be correlated with important clinical adverse events.

  10. Increases in the serum acute phase proteins after ozone exposure are associated with induction of genes in the lung but not liver

    EPA Science Inventory

    Acute Phase Response (APR), a systemic reaction to infection, trauma, and inflammation, is characterized by increases and decreases in plasma levels of positive and negative acute phase proteins (APP), respectively. Although the liver has been shown to contribute to APR in variou...

  11. Acute phase protein response in the capybara (Hydrochoerus hydrochaeris).

    PubMed

    Bernal, Luis; Feser, Mariane; Martínez-Subiela, Silvia; García-Martínez, Juan D; Cerón, José J; Tecles, Fernando

    2011-10-01

    We evaluated the acute phase protein response in capybaras (Hydrochoerus hydrochaeris). Three animal groups were used: 1) healthy animals (n=30), 2) a group in which experimental inflammation with turpentine was induced (n=6), and 3) a group affected with sarcoptic scabies (n=14) in which 10 animals were treated with ivermectin. Haptoglobin (Hp), acid-soluble glycoprotein (ASG) and albumin were analyzed in all animals. In those treated with turpentine, Hp reached its maximum value at 2 wk with a 2.7-fold increase, whereas ASG increased 1.75-fold and albumin decreased 0.87-fold 1 wk after the induction of inflammation. Capybaras affected with sarcoptic scabies presented increases in Hp and ASG of 4.98- and 3.18-fold, respectively, and a 0.87-fold decrease in albumin, compared with healthy animals. Haptoglobin and ASG can be considered as moderate, positive acute phase proteins in capybaras because they showed less than 10-fold increases after an inflammatory process and reached their peak concentrations 1 wk after the induction of inflammation. Conversely, albumin can be considered a negative acute phase protein in capybaras because it showed a reduction in concentration after inflammatory stimulus.

  12. Involvement of activated leukocytes in the regulation of plasma levels of acute phase proteins in microgravity simulation experiments

    NASA Astrophysics Data System (ADS)

    Larina, Olga; Bekker, Anna; Turin-Kuzmin, Alexey

    2016-07-01

    Earth-based studies of microgravity effects showed the induction of the mechanisms of acute phase reaction (APR). APR comprises the transition of stress-sensitive protein kinases of macrophages and other responsive cells into the active state and the phosphorylation of transcription factors which in turn stimulate the production of acute-phase reaction cytokines. Leukocyte activation is accompanied by the acceleration of the formation of oxygen radicals which can serve a functional indice of leukocyte cell state. The series of events at acute phase response result in selective changes in the synthesis of a number of secretory blood proteins (acute phase proteins, APPs) in liver cells thus contributing the recovery of homeostasis state in the organism. Earlier experiment with head-down tilt showed the increase in plasma concentrations of two cytokine mediators of acute phase response, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) being the outcome of the activation of producer cells, foremost, leukocytes. In experiment with 4-day dry immersion chemiluminescent (ChL) reply of the whole blood samples to a test stimulus were studied along with the measurements of plasma levels of APPs, namely, alpha1-antitrypsin (alpha1-AT), alpha1-acid glycoprotein (alpha1-AGP), alpha2-macroglobulin (alpha2-M), ceruloplasmin (Cer), haptoglobin (Hp), C3-complement component (C3), C-reactive protein (CRP). Eight individuals aged 21.2 ± 3.2 years were the test subjects in the investigation. Protein studies showed a noticeable increase in the mean plasma levels of all APPs measured in experiment thus producing the evidence of the activation of acute phase response mechanisms while individual patterns revealed variability during the immersion period. The overall trends were similar to these in the previous immersion series. The augment in the strength of signal in stimulated light emission tests was higher after 1- and 2-day of immersion exposure than before the

  13. Acute phase serum proteins in syngeneic and allogeneic mouse pregnancy.

    PubMed Central

    Waites, G T; Bell, A M; Bell, S C

    1983-01-01

    The levels of two murine acute phase proteins, serum amyloid P component (SAP) and haptoglobin, have been measured in the serum of C57BL/10 female mice during syngeneic and allogeneic pregnancy. Both syngeneic and allogeneic pregnancy resulted in alterations in the levels of these proteins as compared to those observed in virgin females. Syngeneic mating resulted in an increase in concentration of both proteins during the final 3 days of pregnancy. During allogeneic pregnancy, SAP levels, after a transient increase on day 4, rose from days 6-8 and, after remaining relatively stable, increased from day 12 to reach maximum levels on day 18 of pregnancy. Levels fell dramatically during the immediate post-partum period. In contrast, although levels of haptoglobin also increased from days 6-8, for the remainder of pregnancy these increased levels remained stable. The implications of these findings are discussed in relation to the mechanisms of regulation of acute phase reactants and the immunological relationship between the mother and fetus. PMID:6409477

  14. Acute phase proteins in experimentally induced pregnancy toxemia in goats.

    PubMed

    González, Félix H D; Hernández, Fuensanta; Madrid, Josefa; Martínez-Subiela, Silvia; Tvarijonaviciute, Asta; Cerón, José J; Tecles, Fernando

    2011-01-01

    The present work aimed to study the behavior of acute phase proteins (haptoglobin, serum amyloid A, acid soluble glycoprotein, fibrinogen, and albumin) in fasting-induced pregnancy toxemia in goats and their relationship with classical indicators of this disorder such as beta-hydroxybutyrate and nonesterified fatty acids in the blood and decreased urine pH and ketonuria. Twelve adult Murciano-Granadina goats at the final stage of gestation were used in this experiment. Pregnancy toxemia was induced in 6 goats by fasting for 72 hr. The other 6 animals were used as control group. Ketonuria was present in 4 out of 5 fasting animals at 24 hr and in all fasting animals at 48 hr of fasting. Serum nonesterified fatty acids were significantly increased at 24, 48, and 72 hr of fasting. Beta-hydroxybutyrate and haptoglobin achieved significantly increased concentrations at 48 hr and 72 hr, respectively, remaining increased during the entire study. Serum amyloid A, acid soluble glycoprotein, fibrinogen, and albumin were not affected by fasting. In conclusion, acute phase proteins (including haptoglobin) seemed not to have an advantage over traditional markers in diagnosis of fasting-induced pregnancy toxemia in goats. PMID:21217028

  15. The effect of transport stress on turkey (Meleagris gallopavo) liver acute phase proteins gene expression.

    PubMed

    Marques, Andreia Tomás; Lecchi, Cristina; Grilli, Guido; Giudice, Chiara; Nodari, Sara Rota; Vinco, Leonardo J; Ceciliani, Fabrizio

    2016-02-01

    The aim of this study was to investigate the effects of transport-related stress on the liver gene expression of four acute phase proteins (APP), namely α1-acid glycoprotein (AGP), C-Reactive Protein (CRP), Serum Amyloid A (SAA) and PIT54, in turkeys (Meleagris gallopavo). A group of seven BUT BIG 6 commercial hens was subjected to a two-hour long road transportation and the quantitative gene expression of APP in the liver was compared to that of a non transported control group. The expression of AGP and CRP mRNA was found to be increased in animals slaughtered after road transport. The presence of AGP protein was also confirmed by immunohistochemistry and Western blotting. The results of this study showed that road-transport may induce the mRNA expression of immune related proteins. The finding that AGP and CRP can be upregulated during transport could suggest their use as for the assessment of turkey welfare during transport.

  16. Potential of acute phase proteins as predictor of postpartum uterine infections during transition period and its regulatory mechanism in dairy cattle

    PubMed Central

    Manimaran, A.; Kumaresan, A.; Jeyakumar, S.; Mohanty, T. K.; Sejian, V.; Kumar, Narender; Sreela, L.; Prakash, M. Arul; Mooventhan, P.; Anantharaj, A.; Das, D. N.

    2016-01-01

    Among the various systemic reactions against infection or injury, the acute phase response is the cascade of reaction and mostly coordinated by cytokines-mediated acute phase proteins (APPs) production. Since APPs are sensitive innate immune molecules, they are useful for early detection of inflammation in bovines and believed to be better discriminators than routine hematological parameters. Therefore, the possibility of using APPs as a diagnostic and prognostic marker of inflammation in major bovine health disorders including postpartum uterine infection has been explored by many workers. In this review, we discussed specifically importance of postpartum uterine infection, the role of energy balance in uterine infections and potential of APPs as a predictor of postpartum uterine infections during the transition period and its regulatory mechanism in dairy cattle. PMID:27051191

  17. Emerging roles of the acute phase protein pentraxin-3 during central nervous system disorders.

    PubMed

    Rajkovic, Ivana; Denes, Adam; Allan, Stuart M; Pinteaux, Emmanuel

    2016-03-15

    Pentraxin-3 (PTX3) is an acute phase protein (APP) and a member of the long pentraxin family that is recognised for its role in peripheral immunity and vascular inflammation in response to injury, infection and diseases such as atherosclerosis, cancer and respiratory disease. Systemic levels of PTX3 are highly elevated in these conditions, and PTX3 is now recognised as a new biomarker of disease risk and progression. There is extensive evidence demonstrating that central nervous system (CNS) disorders are primarily characterised by central activation of innate immunity, as well as activation of a potent peripheral acute phase response (APR) that influences central inflammation and contributes to poor outcome. PTX3 has been recently recognised to play important roles in CNS disorders, having both detrimental and neuroprotective effects. The present review aims to give an up-to-date account of the emerging roles of PTX3 in CNS disorders, and to provide a critical comparison between peripheral and central actions of PTX3 in inflammatory diseases.

  18. Acute phase protein and antioxidant responses in dogs with experimental acute monocytic ehrlichiosis treated with rifampicin.

    PubMed

    Karnezi, Dimitra; Ceron, Jose J; Theodorou, Konstantina; Leontides, Leonidas; Siarkou, Victoria I; Martinez, Silvia; Tvarijonaviciute, Asta; Harrus, Shimon; Koutinas, Christos K; Pardali, Dimitra; Mylonakis, Mathios E

    2016-02-29

    There is currently lack of information on the changes of acute phase proteins (APP) and antioxidant markers and their clinical relevance as treatment response indicators in canine monocytic ehrlichiosis (CME). The objective of this study was to investigate the patterns of C-reactive protein (CRP), haptoglobin (Hp), ferritin and paraoxonase-1 (PON-1) during treatment of dogs with acute CME with rifampicin. Blood serum samples from ten Beagle dogs with experimental acute CME were retrospectively examined. Five dogs (Group A) were treated with rifampicin (10mg/Kg/24h), per os, for 3 weeks and 5 dogs (Group B) received no treatment (infected controls). Two Beagle dogs served as uninfected controls. Blood serum samples were serially examined prior to Ehrlichia canis inoculation and on post-inoculation days 14, 21, 28, 35 and 42. Significant changes of CRP, Hp, ferritin and PON-1 values were found in the majority of infected dogs. However, their concentrations did not differ between the two groups during the treatment observation period. The results of this study indicate that although several APP and PON-1 tend to significantly change in the majority of dogs with acute CME, they were of limited clinical relevance as treatment response indicators in this experimental setting.

  19. Acute phase protein and antioxidant responses in dogs with experimental acute monocytic ehrlichiosis treated with rifampicin.

    PubMed

    Karnezi, Dimitra; Ceron, Jose J; Theodorou, Konstantina; Leontides, Leonidas; Siarkou, Victoria I; Martinez, Silvia; Tvarijonaviciute, Asta; Harrus, Shimon; Koutinas, Christos K; Pardali, Dimitra; Mylonakis, Mathios E

    2016-02-29

    There is currently lack of information on the changes of acute phase proteins (APP) and antioxidant markers and their clinical relevance as treatment response indicators in canine monocytic ehrlichiosis (CME). The objective of this study was to investigate the patterns of C-reactive protein (CRP), haptoglobin (Hp), ferritin and paraoxonase-1 (PON-1) during treatment of dogs with acute CME with rifampicin. Blood serum samples from ten Beagle dogs with experimental acute CME were retrospectively examined. Five dogs (Group A) were treated with rifampicin (10mg/Kg/24h), per os, for 3 weeks and 5 dogs (Group B) received no treatment (infected controls). Two Beagle dogs served as uninfected controls. Blood serum samples were serially examined prior to Ehrlichia canis inoculation and on post-inoculation days 14, 21, 28, 35 and 42. Significant changes of CRP, Hp, ferritin and PON-1 values were found in the majority of infected dogs. However, their concentrations did not differ between the two groups during the treatment observation period. The results of this study indicate that although several APP and PON-1 tend to significantly change in the majority of dogs with acute CME, they were of limited clinical relevance as treatment response indicators in this experimental setting. PMID:26854345

  20. Acute phase protein response in heartworm-infected dogs after adulticide treatment.

    PubMed

    Méndez, J C; Carretón, E; Martínez-Subiela, S; Tvarijonaviciute, A; Cerón, J J; Montoya-Alonso, J A

    2015-04-30

    During the adulticide treatment of Dirofilaria immitis the worms die releasing fragments of parasites and causing pulmonary thromboembolisms which could exacerbate the clinical condition. To determine the utility of acute phase proteins (APPs) to monitor the progression of the treatment, different positive [C-reactive protein (CRP), haptoglobin (hp)] and negative [albumin, paraoxonase-1(PON-1)] APPs were measured in 15 heartworm-infected dogs (5 with high and 10 with low parasite burden) following adulticide treatment. The results showed increased concentrations of CRP, decreased concentrations of haptoglobin and PON-1 in infected dogs before starting the treatment. Progressive but not significant increases were observed in PON-1 activity and albumin concentration along the treatment. After the treatment with doxycycline and ivermectine a decrease in CRP and Hp levels was experienced, which could reflect a reduction of the vascular inflammation caused by the elimination of Wolbachia and reduction of microfilariae. Fifteen days after the first melarsomine injection, marked increases in CRP and Hp were observed, which could be due to pulmonary inflammation and thromboembolism caused by the post-adulticide death of the worms. This increase was greater in dogs with high parasite burden. As the pathology disappeared, there was an improvement in the concentrations of CRP and Hp, returning into reference values in dogs with low parasite burden at the end of the treatment. The measurement of CRP and Hp could be a resource of support to evaluate the magnitude of the post-adulticide complications during the adulticide treatment of D. immitis. PMID:25801227

  1. Effects of competition on acute phase proteins and lymphocyte subpopulations - oxidative stress markers in eventing horses.

    PubMed

    Valle, E; Zanatta, R; Odetti, P; Traverso, N; Furfaro, A; Bergero, D; Badino, P; Girardi, C; Miniscalco, B; Bergagna, S; Tarantola, M; Intorre, L; Odore, R

    2015-10-01

    The aim of the study was to evaluate markers of the acute phase response (APR) in eventing horses by measuring acute phase proteins (APP) (haptoglobin, Hp, and serum amyloid A, SAA), lysozyme, protein adducts such as pentosidine-like adducts (PENT), malondialdehyde adducts (MDA), hydroxynonenal adducts (HNE) and total advanced glycation/glycoxidation end products (AGEs), complete blood count and lymphocyte subpopulations (CD4+, CD8+ and CD21+) both at rest and at the end of an eventing competition. Blood samples were collected from eight Warmblood horses (medium age 10 ± 3) during an official national 2-day event competition at rest (R) and 10 min after the arrival of the cross-country test on the second day. Exercise caused a significant increase in red blood cell number, haemoglobin, packed cell volume, neutrophils, white blood cell and lymphocyte number; however, these values remained within the normal range. The CD4+ and CD8+ cells significantly increased, whereas the CD21+ lymphocytes decreased; a significant increase in serum SAA, lysozyme and protein carbonyl derivates was also observed. Two-day event causes significant changes in APR markers such as lysozyme, protein carbonyl derivates (HNE, AGEs, PENT) and lymphocyte subpopulations. The data support the hypothesis that 2-day event may alter significantly APR markers. Limitations of the study were the relatively small sample size and sampling time conditioned by the official regulations of the event. Therefore, further studies are needed to investigate the time required for recovery to basal values in order to define the possible effects on the immune function of the athlete horse.

  2. Periparturient cortisol, acute phase cytokine, and acute phase protein profiles of gilts housed in groups or stalls during gestation.

    PubMed

    Sorrells, A D; Eicher, S D; Harris, M J; Pajor, E A; Richert, B T

    2007-07-01

    Use of gestation stalls in pork production remains a controversial topic in animal welfare. Immune status and measures are frequently used to assess stress levels and thus well-being of confined animals. The important welfare issue of close confinement among gestating gilts was tested by quantifying cortisol, acute phase cytokine, and acute phase protein pro-files before and after farrowing of gilts housed in 2 systems. Landrace x Yorkshire crossbred gilts housed in groups of 4 (group, n = 8) in pens (3.9 x 2.4 m with 4 individual feeding spaces, 9.36 m(2) total or 2.34 m(2)/gilt) were compared with gilts housed in standard industry stalls (stall, n = 16; 2.2 x 0.6 m, 1.32 m(2)/gilt). Floors were fully slatted, and a substrate was not provided for either system. Cortisol was determined from saliva on d 105 of gestation, 1 h after moving the gilts into farrowing stalls (d 111), and 24 h and 7 d after farrowing. Cortisol was greater (P = 0.04) for group gilts compared with stall gilts 1 h after moving them into farrowing stalls and 24 h after farrowing. Cortisol concentrations decreased (P = 0.001) over time. Leukocyte mRNA expression of IL-1, IL-1 receptor antagonist, and tumor necrosis factor-alpha was determined by quantitative, reverse transcription PCR on d 35, 63, and 91 of gestation and 72 h after farrowing. Cytokine mRNA expression of peripheral blood mononuclear cells did not differ between housing systems for IL-1, its receptor antagonist, or for tumor necrosis factor-alpha. Acute phase proteins, including fibrinogen, haptoglobin, and alpha(1)-acid glycoprotein were determined for plasma samples taken at d 35, 63, and 91 of gestation and 72 h and 14 d after farrowing. In contrast to cortisol, plasma fibrinogen concentrations increased (P < 0.005) over time. Haptoglobin did not differ between treatments (P > 0.10). Stall gilts tended to have greater (P = 0.07) plasma alpha(1)-acid glycoprotein concentrations than group animals at d 35 of gestation and d 14

  3. Acute phase protein response during subclinical infection of pigs with H1N1 swine influenza virus.

    PubMed

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Pejsak, Zygmunt

    2012-10-12

    In the present study acute phase proteins (APPs) responses in pigs after subclinical infection with H1N1 swine influenza virus (SwH1N1) were evaluated. Fourteen 5 weeks old, seronegative piglets, both sexes were used. Ten of them were infected intranasally with SwH1N1. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA) and pig major acute phase protein (Pig-MAP) concentrations in serum were measured using commercial ELISAs. No significant clinical signs were observed in any of the infected pigs, however, all infected animals developed specific antibodies against SwH1N1 and viral shedding was observed from 2 to 5 dpi. Only concentrations of Hp and SAA were significantly induced after infection, with mean maximum levels from days 1 to 2 post infection (dpi). The concentrations of CRP and Pig-MAP remained generally unchanged, however in half of infected pigs the concentration of CRP tended to increase at 1 dpi (but without statistical significance). The results of our study confirmed that monitoring of APPs may be useful for detection of subclinically infected pigs. The use of SAA or Hp and Pig-MAP may be a valuable in combination [i.e. Hp (increased concentration) and Pig-MAP (unchanged concentration)] to detect subclinically SIV infected pigs, or to identify pigs actually producing a large amount of virus. Additional studies need to be done in order to confirm these findings.

  4. C-reactive protein, haptoglobin and Pig-Major acute phase protein profiles of pigs infected experimentally by different isolates of porcine reproductive and respiratory syndrome virus.

    PubMed

    Saco, Y; Martínez-Lobo, F; Cortey, M; Pato, R; Peña, R; Segalés, J; Prieto, C; Bassols, A

    2016-02-01

    Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) is the etiologic agent of PRRS, one of the most important diseases in swine worldwide. In the present work, the effects of different PRRSV strains were tested on a piglet experimental model to study the induced acute phase response. For this purpose, pigs (n=15 for each group) were intranasally inoculated with one of five PRRSV strains (isolates EU10, 12, 17, 18 from genotype 1 and isolate JA-142 from genotype 2). The acute phase response was monitored by measuring acute phase proteins (APPs). Specifically, the serum concentration of haptoglobin (Hp), C-reactive protein (CRP) and Pig-Major Acute Protein (Pig-MAP) was determined at 0, 3, 6, 9, 12, 15, 18 and 21 days p.i. Clinical signs and growth performance were also monitored during the experiment. All animals became viremic after inoculation during the study period. The APP response was heterogeneous and dependent on the strain, being strains EU10, EU 18 and JA-142 those that induced the highest response and the strongest clinical signs. In general, Hp was the most sensitive biomarker for PRRSV infection, CRP behaved as moderate and Pig-MAP was the less responsive during the course of PRRSV experimental infection. Hp and CRP were significantly discriminatory between infected and control pigs, but not Pig-MAP.

  5. Acute phase proteins increase with sarcoptic mange status and severity in Iberian ibex (Capra pyrenaica, Schinz 1838).

    PubMed

    Ráez-Bravo, Arián; Granados, José Enrique; Cerón, José Joaquín; Cano-Manuel, Francisco Javier; Fandos, Paulino; Pérez, Jesús María; Espinosa, José; Soriguer, Ramón Casimiro; López-Olvera, Jorge Ramón

    2015-11-01

    Sarcoptic mange is a contagious skin disease caused by Sarcoptes scabiei, affecting both domestic and wild mammals, including the Iberian ibex (Capra pyrenaica), a medium-sized mountain ungulate almost endemic to the Iberian Peninsula. Acute phase proteins (APPs) could be an indicator of sarcoptic mange disease and severity in Iberian ibex. Serum samples from 131 healthy and sarcoptic mange-affected Iberian ibexes were collected from 2005 to 2012 in Sierra Nevada Natural Space in southern Spain. Serum alpha-1-acid glycoprotein (AGP), serum amyloid A (SAA) and haptoglobin (Hp) concentrations were quantified, and statistically significant differences according to sarcoptic mange disease and severity were assessed. Both AGP and SAA were significantly higher in the sarcoptic mange-affected ibexes than in the healthy ones as well as in the severely affected ibexes as compared to those with less than 50 % of the body surface affected. For the first time, changes in APP are reported in relation to sarcoptic mange in Iberian ibex. It is also reported for the first time that the intensity of APP increase depends on the severity of sarcoptic mange, which could be related with the pathological secondary amyloidosis, leading to organ dysfunction in severely mange-affected animals. Species and population differences in the increase of APP in response to sarcoptic mange could indicate individual and population differences in the immune capability of each population to deal with mange, population prevalence and mortality being the last indicators of such sensitivity.

  6. Acute-phase proteins in stroke: influences of its cause (cerebral hemorrhage or infarction), of the cerebral site of infarction, and of the sex of patients.

    PubMed

    Ionescu, D A; Haţegan, D; Jipescu, I; Steinbruch, L; Scu, M G

    1991-01-01

    In most of the 129 patients with a recent stroke by cerebral hemorrhage or infarction a note-worthy acute-phase response was found, as demonstrated by important quantitative alterations of blood levels of several acute-phase proteins (APP). These alterations were different in patients with cerebral hemorrhage as compared to those with cerebral infarction. The alterations due to cerebral infarction were not different according to the site of the infarction in brain, i.e. in the brain territories irrigated by the carotid artery system or by the basilar artery system. The APP alterations do not depend on the sex of patients or on the time elapsed from stroke-onset to blood collection.

  7. Ethionine-dependent inhibition of acute-phase plasma protein synthesis in the rat.

    PubMed Central

    Kasperczyk, H.; Koj, A.

    1983-01-01

    Ethionine administered intraperitoneally to rats suffering from turpentine-induced inflammation preferentially reduced incorporation of 14C-leucine into fibrinogen, haptoglobin and other acute-phase proteins. The inhibitory effect was observed both in vivo and in liver slices obtained from ethionine-treated donors, while addition of ethionine to liver slices in vitro led to general reduction of synthesis of all liver and plasma proteins, including albumin. For comparison, the effects of galactosamine and actinomycin D on plasma protein synthesis in injured rats were also examined. It has been concluded that ethionine acts in the early phases of the acute-phase response, probably by inhibition of trauma-induced transcription of liver mRNA specific for acute-phase proteins. PMID:6882676

  8. [The prognostic value of content of acute phase proteins in development of puerperal endometritis].

    PubMed

    Anokhova, L I; Pateiuk, A V; Zagorodnaia, E D

    2012-07-01

    The analysis was made of the content of proteins in inflammation acute phase in 100 healthy puerperants and 157 women with endometritis after cesarean section. The established disproportion in protein concentration during acute phase in healthy puerperants is considered as a female organism adaptive reaction to pregnancy and delivery. As for patients with endometritis, this condition testifies the compensatory resources stress, development of pathophysiological reactions of organism and intensity of local damages. The concentration of C-reactive protein and prealbumin in patients with endometritis provides an opportunity to forecast the degree of severity of course of disease. PMID:22988794

  9. Acute phase proteins in Andalusian horses infected with Theileria equi.

    PubMed

    Rodríguez, Rocío; Cerón, José J; Riber, Cristina; Castejón, Francisco; Gómez-Díez, Manuel; Serrano-Rodríguez, Juan M; Muñoz, Ana

    2014-10-01

    Clinical and laboratory findings were determined in 23 Andalusian horses in southern Spain that were positive for Theileria equi by PCR, including 16 mares at pasture (group A1) and seven stabled stallions (group B1). Five healthy mares at pasture (group A2) and five stabled stallions (group B2), all of which were negative for T. equi in Giemsa stained blood smears and by PCR, were used as controls. The most frequent clinical signs were anorexia, anaemia, depression and icterus (group A1), along with loss of performance or failure to train and depression (group B1). Thrombocytopoenia was evident in 5/7 horses in group B1. Lower serum iron concentrations were observed in both diseased groups compared with their respective control groups. There were no significant differences in APP concentrations between diseased and control groups; all affected horses had APP concentrations within reference limits. Serum haptoglobin, serum amyloid A and plasma fibrinogen concentrations were higher than the reference limits in 5/23, 3/23 and 1/23 diseased horses, respectively. It was concluded that horses with theileriosis exhibited only a mild systemic inflammatory response.

  10. Influence of maternal infections on neonatal acute phase proteins and their interaction in the development of non-affective psychosis

    PubMed Central

    Blomström, Å; Gardner, R M; Dalman, C; Yolken, R H; Karlsson, H

    2015-01-01

    Although primary infections with Toxoplasma gondii or herpes viruses during pregnancy are established teratogens, chronic maternal infections with these pathogens are considered far less serious. However, such chronic infections have been associated with neuropsychiatric disorders in the offspring. The risks of non-affective psychoses, including schizophrenia, in offspring associated with these exposures during pregnancy have not been completely defined. We used data from neonatal dried blood samples from 199 cases of non-affective psychosis and 525 matched controls (born 1975–1985). We measure immunoglobulin G antibodies directed at T. gondii, cytomegalovirus and herpes simplex virus type-1 and -2, as well as levels of nine acute phase proteins (APPs). We assessed the interaction between maternal antibodies and neonatal APP in terms of risk of non-affective psychosis. Among controls, maternal exposure to T. gondii or cytomegalovirus, but not to the other herpes viruses, was associated with significantly higher levels of neonatal APPs. Among cases, none of the maternal exposures were associated with any significant change in APPs. We observed increased RR for non-affective psychosis associated with maternal infection with T. gondii (odds ratio 2.1, 95% confidence interval 1.1–4.0) or cytomegalovirus (1.7, 0.9–3.3) only among neonates with low APP levels. These findings suggest that chronic maternal infection with T. gondii or cytomegalovirus affect neonatal markers of innate immunity. Deficient fetal immune responses in combination with maternal chronic infections may contribute to subsequent risk for psychosis. A greater understanding of the maternal–fetal immunological interplay may ultimately lead to preventive strategies toward neuropsychiatric disorders. PMID:25646591

  11. ACUTE PHASE PROTEIN AND ELECTROPHORESIS PROTEIN FRACTION VALUES FOR CAPTIVE AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER).

    PubMed

    Delk, Katie W; Wack, Raymund F; Burgdorf-Moisuk, Anne; Kass, Philip H; Cray, Carolyn

    2015-12-01

    Protein electrophoresis has recognized applications in determining the health status of various species. While reference intervals for electrophoresis have been determined for psittacine and raptor species, there are none reported for Phoenicopteriformes species. Reference intervals for haptoglobin and protein fractions obtained by electrophoresis were determined for the American flamingo (Phoenicopterus ruber) based on plasma samples from 39 captive birds. The reference intervals were as follows: haptoglobin, 0.17-0.8 mg/ml; total protein, 3.65-6.38 g/dl; prealbumin, 0.26-1.9 g/dl; albumin, 1.51-3.12 g/dl; α-1 globulin, 0.06-0.38 g/dl; α-2 globulin, 0.17-0.67 g/dl; β globulin, 0.38-1.33 g/dl; γ globulin, 0.26-0.68 g/dl; albumin : globulin ratio, 0.93-2.17. As captive flamingos often suffer from pododermatitis, feet of all flamingos were scored to determine if pododermatitis would be reflected in the acute phase proteins. Spearman rank correlation was performed on each of the protein fractions and pododermatitis scores, and only albumin had a significant correlation. This indicates that albumin, as a negative acute phase protein, may be a marker for this disease process.

  12. The diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis.

    PubMed

    El-Deeb, Wael M; Elmoslemany, Ahmed M

    2016-01-01

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring pneumonic pasteurellosis in sheep. PMID:27547520

  13. The diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis

    PubMed Central

    Elmoslemany, Ahmed M.

    2016-01-01

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring pneumonic pasteurellosis in sheep. PMID:27547520

  14. C-reactive protein and the acute phase reaction in geriatric patients.

    PubMed

    Bertsch, Thomas; Triebel, Jakob; Bollheimer, Cornelius; Christ, Michael; Sieber, Cornel; Fassbender, Klaus; Heppner, Hans Jürgen

    2015-10-01

    The C-reactive protein (CRP), first described as a serum component capable of precipitating the C-polysaccharide of pneumococci, is one of the most important proteins because the serum concentration rises in the acute phase reaction. The acute phase reaction is the nonspecific reaction of the body to noxious stimuli of the most varied kinds, such as infections, burns, neoplasms and tissue trauma. The CRP is synthesized in liver parenchymal cells by cytokines which are derived from stimulated leucocytes and released into the circulation. Because of its molecular structure and in synergy with the complement system, it is able to precipitate and/or lyse microorganisms, thereby rendering them harmless. Measurement of the serum CRP concentration can provide important information with respect to the diagnosis and monitoring of treatment. Due to immunosenescence in geriatric patients the synthesis of CRP appears to be limited to inflammatory stimuli; however, this phenomenon does not appear to be of major clinical relevance. Despite the introduction of new parameters of the acute phase reaction, sometimes with better performance, such as interleukin-6, procalcitonin and the soluble endotoxin receptor sCD14, measurement of CRP for diagnosis and treatment monitoring is still justified even in geriatric patients as testing is rapid, economic and nearly ubiquitously available round the clock. Biochemical markers of the acute phase reaction should always be interpreted together with the clinical picture and their specific limitations.

  15. Ceruloplasmin: macromolecular assemblies with iron-containing acute phase proteins.

    PubMed

    Samygina, Valeriya R; Sokolov, Alexey V; Bourenkov, Gleb; Petoukhov, Maxim V; Pulina, Maria O; Zakharova, Elena T; Vasilyev, Vadim B; Bartunik, Hans; Svergun, Dmitri I

    2013-01-01

    Copper-containing ferroxidase ceruloplasmin (Cp) forms binary and ternary complexes with cationic proteins lactoferrin (Lf) and myeloperoxidase (Mpo) during inflammation. We present an X-ray crystal structure of a 2Cp-Mpo complex at 4.7 Å resolution. This structure allows one to identify major protein-protein interaction areas and provides an explanation for a competitive inhibition of Mpo by Cp and for the activation of p-phenylenediamine oxidation by Mpo. Small angle X-ray scattering was employed to construct low-resolution models of the Cp-Lf complex and, for the first time, of the ternary 2Cp-2Lf-Mpo complex in solution. The SAXS-based model of Cp-Lf supports the predicted 1:1 stoichiometry of the complex and demonstrates that both lobes of Lf contact domains 1 and 6 of Cp. The 2Cp-2Lf-Mpo SAXS model reveals the absence of interaction between Mpo and Lf in the ternary complex, so Cp can serve as a mediator of protein interactions in complex architecture. Mpo protects antioxidant properties of Cp by isolating its sensitive loop from proteases. The latter is important for incorporation of Fe(3+) into Lf, which activates ferroxidase activity of Cp and precludes oxidation of Cp substrates. Our models provide the structural basis for possible regulatory role of these complexes in preventing iron-induced oxidative damage. PMID:23843990

  16. Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant

    SciTech Connect

    Liu Zhilin; Ukomadu, Chinweike

    2008-01-25

    Fibrinogen-like protein 1 (FGL1) is a hepatocyte derived protein that is upregulated in regenerating rodent livers following partial hepatectomy. It has been implicated as a mitogen for liver cell proliferation. In this study, we show that recombinant human IL-6 induces FGL1 expression in Hep G2 cells in a pattern similar to those of acute phase reactants. Following induction of acute inflammation in rats by subcutaneous injection of turpentine oil, serum FGL1 levels are also enhanced. Although, a recent report suggests that FGL1 associates almost exclusively with the fibrin matrix, we report here that approximately 20% of the total plasma FGL1 remains free. The enhancement of FGL1 levels in vitro by IL-6 and its induction after turpentine oil injection suggest that it is an acute phase reactant. Its presence in bound and free forms in the blood also implies biological roles that extend beyond the proposed autocrine effect it has on hepatocytes during regeneration.

  17. Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer.

    PubMed

    Panis, Carolina; Pizzatti, Luciana; Bufalo, Aedra Carla; Herrera, Ana Cristina; Victorino, Vanessa Jacob; Cecchini, Rubens; Abdelhay, Eliana

    2016-03-01

    Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1β, IL-12, TGF-β1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment.

  18. The role and importance of glycosylation of acute phase proteins with focus on alpha-1 antitrypsin in acute and chronic inflammatory conditions.

    PubMed

    McCarthy, Cormac; Saldova, Radka; Wormald, Mark R; Rudd, Pauline M; McElvaney, Noel G; Reeves, Emer P

    2014-07-01

    Acute phase proteins (APPs) are a group of circulating plasma proteins which undergo changes quantitatively or qualitatively at the time of inflammation. Many of these APPs are glycosylated, and it has been shown that alterations in glycosylation may occur in inflammatory and malignant conditions. Changes in glycosylation have been studied as potential biomarkers in cancer and also in chronic inflammatory conditions and have been shown to correlate with disease severity in certain conditions. Serine protease inhibitors (serpins), many of which are also APPs, are proteins involved in the control of proteases in numerous pathways. Alpha-1 Antitrypsin (AAT) is the most abundant serpin within the circulation and is an APP which has been shown to increase in response to inflammation. The primary role of AAT is maintaining the protease/antiprotease balance in the lung, but it also possesses important anti-inflammatory and immune-modulating properties. Several glycoforms of AAT exist, and they possess differing properties in regard to plasma half-life and stability. Glycosylation may also be important in determining the immune modulatory properties of AAT. The review will focus on the role and importance of glycosylation in acute phase proteins with particular attention to AAT and its use as a biomarker of disease. The review describes the processes involved in glycosylation, how glycosylation changes in differing disease states, and the alterations that occur to glycans of APPs with disease and inflammation. Finally, the review explores the importance of changes in glycosylation of AAT at times of inflammation and in malignant conditions and how this may impact upon the functions of AAT.

  19. Acute phase proteins: a potential approach for diagnosing chronic infection by Trypanosoma vivax.

    PubMed

    Almeida, Katyane de Sousa; Costa, Alinny Ferreira; Silva, Paulo Cesar da; Fagliari, José Jurandir; Machado, Rosangela Zacarias; Nascimento, Adjair Antonio do

    2012-01-01

    The present study aimed to assess potential changes in acute phase proteins in sheep experimentally infected with Trypanosoma vivax. There were studied eight male sheep, four used as controls and four infected with 10(5) T. vivax trypomastigotes. Blood samples were collected at two points times before infection and then at 5,7, 9, 11, 13, 15, 20, 30, 45, 60, 75, 90, 105 and 120 days post-infection (dpi). Blood samples were centrifuged and allotted, and acute phase proteins were then separated by electrophoresis on acrylamide gel containing sodium dodecyl sulfate. Protein concentrations were determined by computer-assisted densitometry. Total protein was determined by colorimetric biuret method. Trypanosomes were counted daily using a 5 mL aliquot of blood smear on a glass slide under a 22 × 22 mm coverslip. Parasites were counted in 100 microscopic fields (40× magnification), and then multiplied by a correction factor. The results were expressed as parasites per mL of blood. For statistical analyses, we used the Wilcoxon test at 5% significance level. There was found a reduction in several acute phase proteins and increase in antitrypsin and transferrin. This finding can be used for the diagnosis of T. vivax infection, especially in chronic infection.

  20. Changes in some acute phase protein and immunoglobulin concentrations in cats affected by feline infectious peritonitis or exposed to feline coronavirus infection.

    PubMed

    Giordano, A; Spagnolo, V; Colombo, A; Paltrinieri, S

    2004-01-01

    The possible role of some acute phase proteins (APPs) and immunoglobulins in both the pathogenesis and diagnosis of feline infectious peritonitis (FIP) has been investigated. Serum protein electrophoresis and the concentration of haptoglobin (Hp), serum amyloid A (SAA), alpha(1)-acid glycoprotein (AGP), IgG and IgM were evaluated in cats exposed to feline coronavirus (FCoV) and in cats with FIP. The highest concentration of APPs was detected in affected cats, confirming the role of these proteins in supporting a clinical diagnosis of FIP. Repeated samplings from both FIP affected and FCoV-exposed cats showed that when FIP appeared in the group, all the cats had increased APP levels. This increase persisted only in cats that developed FIP (in spite of a decrease in alpha(2)-globulins) but it was only transient in FCoV-exposed cats, in which a long lasting increase in alpha(2)-globulins was observed. These results suggest that changes in the electrophoretic motility of APPs or APPs other than Hp, SAA and AGP might be involved in the pathogenesis of FIP or in protecting cats from the disease.

  1. Serum acute phase proteins in control and Theileria annulata infected water buffaloes (Bubalus bubalis).

    PubMed

    El-Deeb, Wael M; Iacob, Olimpia C

    2012-11-23

    This study was carried out to ascertain the changes in acute phase proteins (APPs) and pro-inflammatory cytokines in Theileria annulata infected water buffalo. Thirty infected water buffaloes and 20 parasitologically free were used. In the present study there was significant (P ≤ 0.05) increase in haptoglobin (Hp), serum amyloid A (SAA), ceruloplasmin, α1-acid glycoprotein (AGP) and fibrinogen levels (2.18 ± 0.29 g/l, 156.58 ± 3.48 mg/l, 31.23 ± 1.25mg/dl, 370.23 ± 33.21 mg/l and 16.17 ± 1.18 g/l, respectively) in T. annulata infected water buffaloes when compared to healthy ones (0.13 ± 0.01 g/l, 23.9 ± 0.56 mg/l, 21.23 ± 1.21 mg/dl, 240.53 ± 22.45 mg/l and 4.2 ± 0.1 6g/l, respectively). Moreover, there was significant (P ≤ 0.05) increase in the levels of TNF-α, IL-1α, IL-6, IL-12, IL-1β and IFN-γ (2.55 ± 0.12 ng/ml, 98.32 ± 4.21 pg/ml, 152.32 ± 5.62 pg/ml, 26.44 ± 1.43 ng/ml, 240.33 ± 20.45 pg/ml and 123.65 ± 5.67 pg/ml, respectively) in T. annulata infected water buffaloes when compared to healthy ones (0.42 ± 0.04 ng/ml, 55.32 ± 3.21 pg/ml, 88.23 ± 3.21 pg/ml, 7.45 ± 0.67 ng/ml, 98.33 ± 3.45 pg/ml and 34.76 ± 1.56 pg/ml, respectively). There was also significant decrease (P ≤ 0.05) in the Hb content, PCV%, RBCs and WBCs counts in the diseased water buffaloes compared to the control ones. Neutropenia, eosinopenia, lymphopenia, monocytopenia and thrombocytopenia were also recorded. The biochemical changes revealed significant (P ≤ 0.05) elevation in the levels of AST, ALT, ALP, LDL-c, VLDL-c, BHBA and NEFA, with significant (P ≤ 0.05) decrease in the levels of total proteins, albumin, globulins, cholesterol, triglyceride, glucose, G6PD, calcium and phosphorus in T. annulata infected water buffaloes when compared to healthy ones. It could be concluded that APPs and pro-inflammatory cytokines could be used as a valuable biomarkers in T. annulata infected water buffaloes (Bubalus bubalis).

  2. Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 1. High abundance proteins, acute phase proteins and peptidomics.

    PubMed

    Thomas, Funmilola Clara; Mullen, William; Tassi, Riccardo; Ramírez-Torres, Adela; Mudaliar, Manikhandan; McNeilly, Tom N; Zadoks, Ruth N; Burchmore, Richard; David Eckersall, P

    2016-08-16

    A peptidomic investigation of milk from an experimental model of Streptococcus uberis mastitis in dairy cows has incorporated a study of milk high abundance and acute phase (APP) proteins as well as analysis of low molecular weight peptide biomarkers. Intramammary infection (IMI) with S. uberis caused a shift in abundance from caseins, β-lactoglobulin and α-lactalbumin to albumin, lactoferrin and IgG with the increase in lactoferrin occurring last. The APP response of haptoglobin, mammary associated serum amyloid A3 and C-reactive protein occurred between 30-48 hours post challenge with peak concentrations of APPs at 72-96 hours post challenge and declined thereafter at a rate resembling the fall in bacterial count rather than the somatic cell count. A peptide biomarker panel for IMI based on capillary electrophoresis and mass spectrometry was developed. It comprised 77 identified peptides (IMI77) composed mainly of casein derived peptides but also including peptides of glycosylation dependent cell adhesion molecule and serum amyloid A. The panel had a biomarker classification score that increased from 36 hour to 81 hour post challenge, significantly differentiating infected from non-infected milk, thus suggesting potential as a peptide biomarker panel of bovine mastitis and specifically that of S. uberis origin. The use of omic technology has shown a multifactorial cross system reaction in high and low abundance proteins and their peptide derivatives with changes of over a thousand fold in analyte levels in response to S. uberis infection. PMID:27412456

  3. ACUTE PHASE PROTEINS AS A MARKER OF RESPIRATORY INFLAMMATION IN PRZEWALSKI'S HORSE (EQUUS FERUS PRZEWALSKII).

    PubMed

    Sander, Samantha J; Joyner, Priscilla H; Cray, Carolyn; Rotstein, David S; Aitken-Palmer, Copper

    2016-06-01

    Acute phase proteins are sensitive markers of inflammation, which are highly conserved across taxa. Although the utility of these proteins are becoming well defined in human and domestic animal medical fields, their role in nondomestic species remains unclear. In this communication, a 20-yr-old Przewalski's horse was presented for unresolving aspiration pneumonia, which cultured a unique Actinomyces-like bacteria. Despite waxing and waning clinical signs and minimal changes on baseline hematologic analysis, protein electrophoresis, serum amyloid A, and surfactant protein D serum concentrations showed changes that more accurately reflected the clinical severity of this case. PMID:27468045

  4. ACUTE PHASE PROTEINS AS A MARKER OF RESPIRATORY INFLAMMATION IN PRZEWALSKI'S HORSE (EQUUS FERUS PRZEWALSKII).

    PubMed

    Sander, Samantha J; Joyner, Priscilla H; Cray, Carolyn; Rotstein, David S; Aitken-Palmer, Copper

    2016-06-01

    Acute phase proteins are sensitive markers of inflammation, which are highly conserved across taxa. Although the utility of these proteins are becoming well defined in human and domestic animal medical fields, their role in nondomestic species remains unclear. In this communication, a 20-yr-old Przewalski's horse was presented for unresolving aspiration pneumonia, which cultured a unique Actinomyces-like bacteria. Despite waxing and waning clinical signs and minimal changes on baseline hematologic analysis, protein electrophoresis, serum amyloid A, and surfactant protein D serum concentrations showed changes that more accurately reflected the clinical severity of this case.

  5. Transport proteins and acute phase reactant proteins in children with sickle cell anemia.

    PubMed Central

    Warrier, R. P.; Kuvibidila, S.; Gordon, L.; Humbert, J.

    1994-01-01

    Transport proteins, acute-phase reactant proteins (APRP), hematology, and anthropometry were studied in 34 sickle cell disease (SCD) children (20 boys, 14 girls) and 27 controls without growth deficits (13 boys, 14 girls) [corrected]. The age range was 1/2 to 16 1/2 years. Weight deficits (< 80%) by Waterlow's classification were observed in 41% of SCD boys and 25% of SCD girls, and height deficits (< 90%) were observed in 25% SCD boys and 25% girls. Mean white blood cell counts were significantly higher (P < .001) and hematocrit and hemoglobin (Hb) lower (P < .005) in SCD children than in controls. Although both groups had similar mean levels of albumin, transferrin, and APRP, SCD children had significantly lower mean levels of retinol-binding protein (RBP) (P < .001) and retinol-prealbumin (P < .001). Retinol-binding protein levels were abnormal in 18 (53%) SCD children and in only 23% controls (chi 2 = 14.06; P < 0.005); transferrin levels were abnormal in 20% of SCD children and in none of the controls. Children with SC and SF Hb phenotype had normal mean levels of RBP, whereas those with S beta thal and SS phenotype had levels below normal. Growth-retarded children by weight and height had reduced mean levels of RBP and prealbumin compared with growth-normal SCD children. The implication of primary protein-energy malnutrition on growth retardation in SCD children is under study. PMID:7512147

  6. Similarities in acute phase protein response during hibernation in black bears and major depression in humans: A response to underlying metabolic depression?

    USGS Publications Warehouse

    Tsiouris, J.A.; Chauhan, V.P.S.; Sheikh, A.M.; Chauhan, A.; Malik, M.; Vaughan, M.R.

    2004-01-01

    This study investigated the effects of hibernation with mild hypothermia and the stress of captivity on levels of six acute-phase proteins (APPs) in serial samples of serum from 11 wild and 6 captive black bears (Ursus americanus Pallas, 1780) during active and hibernating states. We hypothesize that during hibernation with mild hypothermia, bears would show an APP response similar to that observed in major depression. Enzyme-linked immunoabsorbent assay was used to measure alpha2-macroglobulin and C-reactive protein, and a nephelometer to measure alpha1-antitrypsin, haptoglobin, ceruloplasmin, and transferrin. Levels of all other proteins except ceruloplasmin were significantly elevated during hibernation in both wild and captive bears at the p < 0.05 to p < 0.001 level. Alpha 2-macroglobulin and C-reactive-protein levels were increased in captive versus wild bears in both active and hibernating states at the p < 0.01 to p < 0.0001 level. During hibernation with mild hypothermia, black bears do not show immunosuppression, but show an increased APP response similar to that in patients with major depression. This APP response is explained as an adaptive response to the underlying metabolic depression in both conditions. Metabolic depression in hibernating bears is suggested as a natural model for research to explain the neurobiology of depression.

  7. The Acute-Phase Proteins Serum Amyloid A and C Reactive Protein in Transudates and Exudates

    PubMed Central

    Okino, Alessandra M.; Bürger, Cristiani; Cardoso, Jefferson R.; Lavado, Edson L.; Lotufo, Paulo A.; Campa, Ana

    2006-01-01

    The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA), in comparison with C reactive protein (CRP) and total protein (TP), can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic) and in 12 transudates (9 pleural and 3 ascitic). CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10% of the amount found in serum, that is, the exudate/serum ratio (E/S) was 0.10 ± 0.13. For comparison, the exudate/serum ratio for CRP and TP was 0.39 ± 0.37 and 0.68 ± 0.15, respectively. There was a strong positive correlation between serum and exudate SAA concentration (r = 0.764;p < 0.0001). The concentration of SAA in transudates was low and did not overlap with that found in exudates (0.02-0.21 versus 0.8–360.5 g/mL). SAA in pleural and ascitic exudates results mainly from leakage of the serum protein via the inflamed membrane. A comparison of the E/S ratio of SAA and CRP points SAA as a very good marker in discriminating between exudates and transudates. PMID:16864904

  8. Acute phase proteins as biomarkers of urinary tract infection in dairy cows: diagnostic and prognostic accuracy.

    PubMed

    El-Deeb, Wael M; Elmoslemany, Ahmed M

    2016-02-01

    The aims of this study were to investigate the level of acute phase proteins in dairy cows with urinary tract infection (UTI) and to evaluate their diagnostic and prognostic value. Eighty-four lactating cows with clinical and laboratory evidence of UTI and 15 healthy controls were included in this study. Serum samples were evaluated for the levels of Haptoglobin (Hp), serum amyloid A (SAA), fibrinogen (Fb), α1-Acid glycoprotein (AGP), total protein, and globulin. The diagnostic and prognostic performance of each parameter was evaluated by estimating the area under receiver operating characteristics curve (AUROC). Escherichia coli and Corynebacterium spp. were the primary bacteria associated with UTI. The levels of serum Hp, SAA, Fb, AGP, total protein, and globulin were significantly higher in UTI cows. Successfully treated cows (n = 51) had lower levels of Hp, SAA, AGP, total protein, and globulin than non-responsive cows. Overall, Hp, SAA, Fb, and AGP showed comparable diagnostic accuracy (AUROC ranged from 0.93 to 0.98). Both Hp and SAA showed high accuracy in predicting treatment response (AUROC > 0.95), whereas Fb level was of no prognostic value (AUROC = 0.48). From this study, acute phase proteins levels can be used as markers for UTI in cows and higher levels of Hp, SAA and AGP are related to poor treatment response. PMID:27348889

  9. Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer.

    PubMed

    Panis, Carolina; Pizzatti, Luciana; Bufalo, Aedra Carla; Herrera, Ana Cristina; Victorino, Vanessa Jacob; Cecchini, Rubens; Abdelhay, Eliana

    2016-03-01

    Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1β, IL-12, TGF-β1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment. PMID:26472721

  10. HIV infection and drugs of abuse: role of acute phase proteins

    PubMed Central

    2013-01-01

    Background HIV infection and drugs of abuse such as methamphetamine (METH), cocaine, and alcohol use have been identified as risk factors for triggering inflammation. Acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) are the biomarkers of inflammation. Hence, the interactive effect of drugs of abuse with acute phase proteins in HIV-positive subjects was investigated. Methods Plasma samples were utilized from 75 subjects with METH use, cocaine use, alcohol use, and HIV-positive alone and HIV-positive METH, cocaine, and alcohol users, and age-matched control subjects. The plasma CRP and SAA levels were measured by ELISA and western blot respectively and the CD4 counts were also measured. Results Observed results indicated that the CRP and SAA levels in HIV-positive subjects who are METH, cocaine and alcohol users were significantly higher when compared with either drugs of abuse or HIV-positive alone. The CD4 counts were also dramatically reduced in HIV-positive with drugs of abuse subjects compared with only HIV-positive subjects. Conclusions These results suggest that, in HIV-positive subjects, drugs of abuse increase the levels of CRP and SAA, which may impact on the HIV infection and disease progression. PMID:24044608

  11. Serum protein capillary electrophoresis and measurement of acute phase proteins in a captive cheetah (Acinonyx jubatus) population.

    PubMed

    Depauw, Sarah; Delanghe, Joris; Whitehouse-Tedd, Katherine; Kjelgaard-Hansen, Mads; Christensen, Michelle; Hesta, Myriam; Tugirimana, Pierrot; Budd, Jane; Dermauw, Veronique; Janssens, Geert P J

    2014-09-01

    Renal and gastrointestinal pathologies are widespread in the captive cheetah (Acinonyx jubatus) population but are often diagnosed at a late stage, because diagnostic tools are limited to the evaluation of clinical signs or general blood examination. Presently, no data are available on serum proteins and acute-phase proteins in cheetahs during health or disease, although they might be important to improve health monitoring. This study aimed to quantify serum proteins by capillary electrophoresis in 80 serum samples from captive cheetahs, categorized according to health status and disease type. Moreover, serum amyloid A concentrations were measured via a turbidimetric immunoassay validated in domestic cats, whereas haptoglobin and C-reactive protein were determined by non-species-specific functional tests. Cheetahs classified as healthy had serum protein and acute phase protein concentrations within reference ranges for healthy domestic cats. In contrast, unhealthy cheetahs had higher (P < 0.001) serum amyloid A, alpha2-globulin, and haptoglobin concentrations compared with the healthy subgroup. Moreover, serum amyloid A (P = 0.020), alpha2-globulin (P < 0.001) and haptoglobin (P = 0.001) concentrations in cheetahs suffering from chronic kidney disease were significantly greater compared to the reportedly healthy cheetahs. Our study indicates that serum proteins in the cheetah can be analyzed by routine capillary electrophoresis, whereas acute-phase proteins can be measured using available immunoassays or non-species-specific techniques, which are also likely to be applicable in other exotic felids. Moreover, results suggest that serum amyloid A and haptoglobin are important acute-phase proteins in the diseased cheetah and highlight the need to evaluate their role as early-onset markers for disease.

  12. The acute phase response in panic disorder.

    PubMed

    Herrán, Andrés; Sierra-Biddle, Deirdre; García-Unzueta, Maria Teresa; Puente, Jesús; Vázquez-Barquero, José Luis; Antonio Amado, José

    2005-12-01

    An acute-phase response (APR), manifested as an increase of acute-phase proteins has been shown in major depression. Panic disorder (PD) may share some aetiopathogenic mechanisms with depression, but APR has not been studied in this disorder. Forty-one panic patients in the first stages of their illness were compared with 32 healthy subjects of comparable sex, age, and body mass index. Clinical diagnosis was established with the mini international neuropsychiatric interview, and severity with the panic disorder severity scale and the CGI scale. Laboratory determinations included four acute phase proteins (APPs) [albumin, gammaglobulins, fibrinogen, C-reactive-protein (CRP)] and basal cortisol level. Patients were studied after 8-wk follow-up taking selective serotonin reuptake inhibitors (SSRIs) to assess the evolution of the APPs. Gammaglobulin levels were lower, and both cortisol and CRP levels were higher in PD patients than in controls. APP did not differ between patients with or without agoraphobia. At follow-up, patients who responded to SSRIs presented a decrease in albumin levels, and a trend towards a decrease in cortisol and CRP compared with levels at intake. The conclusions of this study are that there is an APR in patients suffering from PD, and this APR tends to diminish after a successful treatment with SSRIs. PMID:15927091

  13. Lack of association of acute phase response proteins with hormone levels and antidepressant medication in perimenopausal depression

    PubMed Central

    2014-01-01

    Background Major depression is associated with higher plasma levels of positive acute-phase proteins, as well as with lower plasma levels of negative acute-phase proteins. The aim of this study is to examine the levels of acute-phase response proteins and whether these levels are influenced by reproductive hormones and antidepressant medication in the perimenopausal depression. Methods Sixty-five women (age range: 40–58 years old) participated in this study. All women were in the perimenopausal phase. The diagnosis of depression was made through a psychiatric interview and with the aid of Hamilton Depression Rating Scale 17 (HAM-D 17). The acute-phase response proteins, such as haptoglobin (HP), transferrine (TRf), α1-antitrypsin, complement protein 3 (C3), complement protein 4 (C4) and C-reactive protein (CRP) and the reproductive hormones, for example follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), were analyzed using standard laboratory methods. Pearson’s correlations were applied to evaluate the relationship between acute-phase proteins and hormones. Results Perimenopausal women were divided into three groups. The first group consisted of normal controls, the second one involved depressed perimenopausal women, who were taking selective serotonin reuptake inhibitors (SSRIs), and the third one included depressed women that were not treated with SSRIs. Depressed women in perimenopause, when being compared to non-depressed women, did not differ as to serum levels of acute-phase proteins. There was a positive correlation between HP and E2 in depressed perimenopausal women, who were not taking SSRIs. Conclusions The lack of association between acute-phase proteins and depressive mood mentioned in this study does not support previous findings in patients with major depression. This negative finding in perimenopausal depression indicates either the absence or a more complex nature of the interactions between acute-phase proteins

  14. Acute phase protein expression during elephant endotheliotropic herpesvirus-1 viremia in Asian elephants (Elephas maximus).

    PubMed

    Stanton, Jeffrey J; Cray, Carolyn; Rodriguez, Marilyn; Arheart, Kristopher L; Ling, Paul D; Herron, Alan

    2013-09-01

    Infection of Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus (EEHV) can be associated with rapid, lethal hemorrhagic disease and has been documented in elephant herds in human care and in the wild. Recent reports describe real-time quantitative polymerase chain reaction (qPCR) assays used to monitor clinically ill elephants and also to detect subclinical EEHV1 infection in apparently healthy Asian elephants. Acute phase proteins have been demonstrated to increase with a variety of infectious etiologies in domesticated mammals but have not yet been described in elephants. In addition, the immune response of Asian elephants to EEHV1 infection has not been described. In this study, whole blood and trunk wash samples representing repeated measures from eight elephants were examined for the presence of EEHV1 using a qPCR assay. Elephants were classified into groups, as follows: whole blood negative and positive and trunk wash negative and positive. Serum amyloid A (SAA) and haptoglobin (HP) levels were compared between these groups. A significant difference in SAA was observed with nearly a threefold higher mean value during periods of viremia (P=0.011). Higher values of SAA were associated with >10,000 virus genome copies/ml EEHV1 in whole blood. There were no significant differences in HP levels, although some individual animals did exhibit increased levels with infection. These data indicate that an inflammatory process is stimulated during EEHV1 viremia. Acute phase protein quantitation may aid in monitoring the health status of Asian elephants.

  15. Acute phase protein expression during elephant endotheliotropic herpesvirus-1 viremia in Asian elephants (Elephas maximus).

    PubMed

    Stanton, Jeffrey J; Cray, Carolyn; Rodriguez, Marilyn; Arheart, Kristopher L; Ling, Paul D; Herron, Alan

    2013-09-01

    Infection of Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus (EEHV) can be associated with rapid, lethal hemorrhagic disease and has been documented in elephant herds in human care and in the wild. Recent reports describe real-time quantitative polymerase chain reaction (qPCR) assays used to monitor clinically ill elephants and also to detect subclinical EEHV1 infection in apparently healthy Asian elephants. Acute phase proteins have been demonstrated to increase with a variety of infectious etiologies in domesticated mammals but have not yet been described in elephants. In addition, the immune response of Asian elephants to EEHV1 infection has not been described. In this study, whole blood and trunk wash samples representing repeated measures from eight elephants were examined for the presence of EEHV1 using a qPCR assay. Elephants were classified into groups, as follows: whole blood negative and positive and trunk wash negative and positive. Serum amyloid A (SAA) and haptoglobin (HP) levels were compared between these groups. A significant difference in SAA was observed with nearly a threefold higher mean value during periods of viremia (P=0.011). Higher values of SAA were associated with >10,000 virus genome copies/ml EEHV1 in whole blood. There were no significant differences in HP levels, although some individual animals did exhibit increased levels with infection. These data indicate that an inflammatory process is stimulated during EEHV1 viremia. Acute phase protein quantitation may aid in monitoring the health status of Asian elephants. PMID:24063088

  16. Glial expression of the {beta}-Amyloid Precursor Protein (APP) in global ischemia

    SciTech Connect

    Banati, R.B.; Gehrmann, J.; Kreutzberg, G.W. ||

    1995-07-01

    The {beta}-amyloid precursor protein (APP) bears characteristics of an acute-phase protein and therefore is likely to be involved in the glial response to brain injury. In the brain, APP is rapidly synthesized by activated glial cells in response to comparatively mild neuronal lesions, e.g., a remote peripheral nerve injury. Perfusion deficits in the brain result largely in neuronal necrosis and are a common condition in elderly patients. This neuronal necrosis is accompanied by a pronounced reaction of astrocytes and microglia, which can also be observed in animal models. We have therefore studied in the rat, immunocytochemically, the induction of APP after 30 min of global ischemia caused by four-vessel occlusion. The postischemic brain injuries were examined at survival times from 12 h to 7 days. From day 3 onward, APP immunoreactivity was strongly induced in the CA{sub 1} and CA{sub 4} regions of the rat dorsal hippocampus as well as in the dorsolateral striatum. In these areas, the majority of APP-immunoreactive cells were reactive glial fibrillary acidic protein (GFAP)-positive astrocytes, as shown by double-immunofluorescence labeling for GFAP and APP. Additionally, small ramified cells, most likely activated microglia, expressed APP immunoreactivity. In contrast, in the parietal cortex, APP immunoreactivity occurred focally in clusters of activated microglia rather than in astrocytes, as demonstrated by double-immunofluorescence labeling for APP and the microglia-binding lectin Griffonia simplicifolia isolectin B{sub 4}. In conclusion, following global ischemia, APP is induced in reactive glial cells with spatial differences in the distribution pattern of APP induction in actrocytes and microglia. 51 refs., 4 figs.

  17. Acute phase proteins and C9 in patients with Behcet's syndrome and aphthous ulcers.

    PubMed Central

    Adinolfi, M; Lehner, T

    1976-01-01

    Estimation of the concentration of C9, C-reactive protein (CRP) and alpha1-antitrypsin in forty sera from patients with Behcet's syndrome and recurrent oral ulcers showed significantly increased amounts of C9 and CRP in Behcet's syndrome. The concentration of C9 was also significantly raised in recurrent oral ulceration, though to a lesser extent than in Behcet's syndrome. The assay C9 and CRP might be useful in the differential diagnosis of Behcet's syndrome, especially from recurrent oral ulcers. It is suggested that during epithelial inflammation in recurrent oral ulcers some of the acute phase proteins are increased and in some patients these may modulate the immunological mechanism in such a way as to induce a transition from focal oral ulceration to the multifocal Behcet's syndrome. PMID:1086750

  18. Inflammatory cytokine and acute phase protein concentrations in the peripheral blood and uterine washings of cows with subclinical endometritis in the late postpartum period.

    PubMed

    Brodzki, Piotr; Kostro, Krzysztof; Krakowski, Leszek; Marczuk, Jan

    2015-06-01

    The aim of the study was to evaluate the concentrations of proinflammatory cytokines: tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), anti-inflammatory cytokine interleukin-10 (IL-10), and acute phase proteins (APPs)--haptoglobin (Hp) and serum amyloid A (SAA) in serum and uterine washings of cows with subclinical endometritis, and compare them to healthy animals. The study was performed on 24 cows on day 60 after delivery. The cows were divided into two groups based on the results of cytological tests: 12 cows with subclinical endometritis and 12 healthy cows. Experimental material consisted of blood serum and uterine washings. The levels of the following cytokines in the study material were determined with ELISA: TNF-α, IL-6, IL-10 and APPs - Hp and SAA. The results show that the levels of TNF-α (p < 0.01), IL-6, IL-10 as well as SAA and Hp were significantly higher in the serum of cows with subclinical endometritis compared to the controls (p < 0.001). Uterine washings had significantly higher levels of IL-6, IL-10, and Hp in the experimental cows compared to the controls (p < 0.001). The demonstrated differences in the concentration of cytokines and APP between cows with subclinical endometritis and healthy cows, in both the serum and uterine washings, may suggest the usefulness of these parameters in the diagnosis of subclinical endometritis in cows in the late postpartum period. PMID:25846950

  19. DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    EPA Science Inventory

    Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

  20. Acute phase proteins in serum and cerebrospinal fluid in the course of bacterial meningitis.

    PubMed

    Paradowski, M; Lobos, M; Kuydowicz, J; Krakowiak, M; Kubasiewicz-Ujma, B

    1995-08-01

    We carried out estimations of the following acute phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein (AAG), alpha-2-ceruloplasmin (CER), and alpha-2-haptoglobin (HPT) in serum and in cerebrospinal fluid (CSF) in patients with bacterial meningitis (BM, n = 30) and viral meningitis (VM, n = 30). We have shown that determinations of concentrations of AAG and CRP in serum and CER in CSF are useful in differentiation between BM and VM. The diagnostic power of these three tests (the areas under their ROC curves equal 0.942, 0.929, and 0.931, respectively) is bigger, though statistically not significantly, than that of traditional parameters of BM in CSF, i.e., total protein concentration and white blood cell count. Determination of AAG, CRP, and AAT in serum is a valuable monitoring marker in the course of BM treatment. Convenience of serum sampling constitutes an advantage over traditional BM parameters in CSF. PMID:8521602

  1. Elimination Half-Lives of Acute Phase Proteins in Rats and Beagle Dogs During Acute Inflammation.

    PubMed

    Kuribayashi, Takashi; Seita, Tetsuro; Momotani, Eiichi; Yamazaki, Shunsuke; Hagimori, Kohei; Yamamoto, Shizuo

    2015-08-01

    The half-lives of typical acute phase proteins in rats and beagle dogs during acute inflammation were investigated. Acute inflammation was induced by injection of turpentine oil in rats and administration of indomethacin in beagle dogs. Serum concentrations of α2-macroglobulin (α2M) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay and α1-acid glycoprotein (AAG) was measured by single radial immunodiffusion. Half-life was calculated as 0.693/elimination rate constant (K). The mean half-lives in the terminal elimination phase of α2M and AAG were 68.1 and 164.8 h, respectively. The half-life of AAG was significantly longer than that of α2M. Mean half-lives in the terminal elimination phase of CRP and AAG were 161.9 and 304.4 h, respectively. The half-life of AAG was significantly longer than that of CRP in beagle dogs. No significant differences in the half-life of AAG were observed between rats and beagle dogs. Furthermore, serum concentrations in the terminal elimination phase could be simulated with the K data acquired in this study.

  2. Metabolizable protein supply modulated the acute-phase response following vaccination of beef steers.

    PubMed

    Moriel, P; Arthington, J D

    2013-12-01

    Our objective was to evaluate the effects of MP supply, through RUP supplementation, on the acute-phase response of beef steers following vaccination. On d 0, Brangus-crossbred steers (n = 24; 173 ± 31 kg; 175 ± 16 d of age) were randomly assigned to receive 1 of 3 isocaloric diets formulated to provide 85, 100, and 115% of the daily MP requirements of a beef steer gaining 0.66 kg of BW daily. Diets were limit-fed at 1.8% of BW (DM basis) and individually provided to steers once daily (0800 h) from d 0 to 29. Steers were weighed on d 0 and 29, following a 12-h period of feed and water withdrawal. On d 7, steers were vaccinated against Mannheimia haemolytica (OneShot, Pfizer), and blood samples were collected on d 0, 7, 8, 10, 14, 21, and 30. Plasma metabolites were analyzed as repeated measures using the MIXED procedure of SAS. Final BW and ADG were similar (P ≥ 0.50) among treatments (mean = 184 ± 9 kg and 0.5 ± 0.08 kg/d, respectively). Effects of time were detected (P < 0.01) for plasma concentrations of all acute-phase proteins, which peaked between d 7 to 14, returning to baseline concentrations by d 29. Treatment effects were not detected (P ≥ 0.19) for plasma concentrations of acid-soluble protein, albumin, fibrinogen, IGF-1 and serum amyloid-A. Plasma concentrations of total protein (TP) and plasma urea nitrogen (PUN) increased (P ≤ 0.05) with increasing supply of MP (87.1, 89.6, and 90.1 ± 1.09 mg TP/mL and 6.1, 8.3, and 10.3 ± 0.41 mg PUN/dL for 85, 100, and 115% MP steers, respectively). From d 10 to 29, steers provided 115% MP had less (P < 0.001) plasma concentrations of ceruloplasmin than steers fed 85 and 100% MP, which had similar plasma ceruloplasmin concentrations. On d 14, plasma concentrations of haptoglobin were greatest (P ≤ 0.06) for steers fed 115% MP, intermediate for 100% MP, and least for 85% MP (0.98, 0.71 and 0.44 ± 0.099 mg/mL, respectively). On d 10, plasma concentrations of creatinine were greater (P = 0.01) for steers

  3. UV Irradiation Accelerates Amyloid Precursor Protein (APP) Processing and Disrupts APP Axonal Transport

    PubMed Central

    Almenar-Queralt, Angels; Falzone, Tomas L.; Shen, Zhouxin; Lillo, Concepcion; Killian, Rhiannon L.; Arreola, Angela S.; Niederst, Emily D.; Ng, Kheng S.; Kim, Sonia N.; Briggs, Steven P.; Williams, David S.

    2014-01-01

    Overexpression and/or abnormal cleavage of amyloid precursor protein (APP) are linked to Alzheimer's disease (AD) development and progression. However, the molecular mechanisms regulating cellular levels of APP or its processing, and the physiological and pathological consequences of altered processing are not well understood. Here, using mouse and human cells, we found that neuronal damage induced by UV irradiation leads to specific APP, APLP1, and APLP2 decline by accelerating their secretase-dependent processing. Pharmacological inhibition of endosomal/lysosomal activity partially protects UV-induced APP processing implying contribution of the endosomal and/or lysosomal compartments in this process. We found that a biological consequence of UV-induced γ-secretase processing of APP is impairment of APP axonal transport. To probe the functional consequences of impaired APP axonal transport, we isolated and analyzed presumptive APP-containing axonal transport vesicles from mouse cortical synaptosomes using electron microscopy, biochemical, and mass spectrometry analyses. We identified a population of morphologically heterogeneous organelles that contains APP, the secretase machinery, molecular motors, and previously proposed and new residents of APP vesicles. These possible cargoes are enriched in proteins whose dysfunction could contribute to neuronal malfunction and diseases of the nervous system including AD. Together, these results suggest that damage-induced APP processing might impair APP axonal transport, which could result in failure of synaptic maintenance and neuronal dysfunction. PMID:24573290

  4. High levels of acute phase proteins and soluble 70 kDa heat shock proteins are independent and additive risk factors for mortality in colorectal cancer

    PubMed Central

    Kocsis, Judit; Mészáros, Tamás; Madaras, Balázs; Tóth, Éva Katalin; Kamondi, Szilárd; Gál, Péter; Varga, Lilian; Prohászka, Zoltán

    2010-01-01

    Recently, we reported that high soluble Hsp70 (sHsp70) level was a significant predictor of mortality during an almost 3-year-long follow-up period in patients with colorectal cancer. This association was the strongest in the group of <70-year-old female patients as well as in those who were in a less advanced stage of the disease at baseline. According to these observations, measurement of the serum level of sHsp70 is a useful, stage-independent prognostic marker in colorectal cancer, especially in patients without distant metastasis. Since many literature data indicated that measurement of C-reactive protein (CRP) and other acute phase proteins (APPs) may also be suitable for predicting the mortality of patients with colorectal cancer, it seemed reasonable to study whether the effect of sHsp70 and other APPs are related or independent. In order to answer this question, we measured the concentrations of CRP as well as of other complement-related APPs (C1 inhibitor, C3, and C9) along with that of the MASP-2 complement component in the sera of 175 patients with colorectal cancer and known levels of sHsp70, which have been used in our previous study. High (above median) levels of CRP, C1 esterase inhibitor (C1-INH), and sHsp70 were found to be independently associated with poor patient survival, whereas no such association was observed with the other proteins tested. According to the adjusted Cox proportional hazards analysis, the additive effect of high sHsp70, CRP, and C1-INH levels on the survival of patients exceeded that of high sHsp70 alone, with a hazard ratio (HR) of 2.83 (1.13–70.9). In some subgroups of patients, such as in females [HR 4.80 (1.07–21.60)] or in ≤70-year-old patients [HR 11.53 (2.78–47.70)], even greater differences were obtained. These findings indicate that the clinical mortality–prediction value of combined measurements of sHsp70, CRP, and C1-INH with inexpensive methods can be very high, especially in specific subgroups of

  5. The use of acute phase proteins for monitoring animal health and welfare in the pig production chain: the validation of an immunochromatographic method for the detection of elevated levels of pig-MAP.

    PubMed

    Piñeiro, Matilde; Morales, Joaquín; Vizcaíno, Elena; Murillo, José Alberto; Klauke, Thorsten; Petersen, Brigitte; Piñeiro, Carlos

    2013-11-01

    The serum concentration of acute phase proteins (APPs) increases in the presence of disease or stress, which makes APPs notable parameters for the global assessment of animal health and welfare. A rapid, immunochromatographic test (ICT) for the detection of elevated levels of pig Major Acute-phase Protein (pig-MAP), one of the main APPs in pigs, was evaluated in more than 1400 pig serum samples obtained from commercial farms. The ICT showed a good performance with a relative sensitivity (Sn) and specificity (Sp) of 94 and 97%, respectively, for a threshold of 1.5mg/mL (comparison with ELISA). Differences in the pig-MAP levels and the number of positive samples with the ICT were observed within the season of sampling, farms, and age groups at one farm, according to the presence of disease or lesions. The ICT was also evaluated in blood samples obtained at slaughter in association with the carcase inspection. The results from this study indicate that the ICT may be used for the evaluation of groups of pigs, after analysing one sub-sample of these pigs, and might be a useful tool in routine health and welfare monitoring programmes aimed to improve the quality of pig production.

  6. Lipopolysaccharide binding protein and serum amyloid A secretion by human intestinal epithelial cells during the acute phase response.

    PubMed

    Vreugdenhil, A C; Dentener, M A; Snoek, A M; Greve, J W; Buurman, W A

    1999-09-01

    The acute phase proteins LPS binding protein (LBP) and serum amyloid A (SAA) are produced by the liver and are present in the circulation. Both proteins have been shown to participate in the immune response to endotoxins. The intestinal mucosa forms a large surface that is continuously exposed to these microbial products. By secretion of antimicrobial and immunomodulating agents, the intestinal epithelium contributes to the defense against bacteria and their products. The aim of this study was to explore the influence of the inflammatory mediators TNF-alpha, IL-6, and IL-1beta on the release of LBP and SAA by intestinal epithelial cells (IEC). In addition, the induction of LBP and SAA release by cell lines of intestinal epithelial cells and hepatic cells was compared. The data obtained show that in addition to liver cells, IEC also expressed LBP mRNA and released bioactive LBP and SAA upon stimulation. Regulation of LBP and SAA release by IEC and hepatocytes was typical for class 1 acute phase proteins, although differences in regulation between the cell types were observed. Endotoxin did not induce LBP and SAA release. Glucocorticoids were demonstrated to strongly enhance the cytokine-induced release of LBP and SAA by IEC, corresponding to hepatocytes. The data from this study, which imply that human IEC can produce LBP and SAA, suggest a role for these proteins in the local defense mechanism of the gut to endotoxin. Furthermore, the results demonstrate that tissues other than the liver are involved in the acute phase response.

  7. The Alzheimer Amyloid Precursor Protein (APP) and Fe65, an APP-Binding Protein, Regulate Cell Movement

    PubMed Central

    Sabo, Shasta L.; Ikin, Annat F.; Buxbaum, Joseph D.; Greengard, Paul

    2001-01-01

    FE65 binds to the Alzheimer amyloid precursor protein (APP), but the function of this interaction has not been identified. Here, we report that APP and FE65 are involved in regulation of cell movement. APP and FE65 colocalize with actin and Mena, an Abl-associated signaling protein thought to regulate actin dynamics, in lamellipodia. APP and FE65 specifically concentrate with β1-integrin in dynamic adhesion sites known as focal complexes, but not in more static adhesion sites known as focal adhesions. Overexpression of APP accelerates cell migration in an MDCK cell wound–healing assay. Coexpression of APP and FE65 dramatically enhances the effect of APP on cell movement, probably by regulating the amount of APP at the cell surface. These data are consistent with a role for FE65 and APP, possibly in a Mena-containing macromolecular complex, in regulation of actin-based motility. PMID:11425871

  8. Effects of supplementation with dietary green tea polyphenols on parasite resistance and acute phase protein response to Haemonchus contortus infection in lambs.

    PubMed

    Zhong, Rong Zhen; Li, Hao Yang; Sun, Hai Xia; Zhou, Dao Wei

    2014-09-15

    The objective of this study was to determine the effects of supplementation with dietary green tea polyphenols (GTPs) on parasite resistance and acute phase protein (APP) response to Haemonchus contortus infection in lambs. Thirty male Ujumqin lambs were randomly assigned to five treatment groups for an 8-week feeding period. Treatments included: (1) uninfected as control, (2) infected but not given GTP (INFGTP0) and (3)-(5) infected and fed 2, 4, or 6g GTP/kg feed (dry matter basis; INFGTP2, INFGTP4, and INFGTP6, respectively). Fecal and blood samples were collected to determine fecal egg count (FEC), packed cell volume (PCV), and APP concentrations. Live weight was measured once every 2 weeks. At the end of the feeding period, lambs were slaughtered to determine the adult H. contortus burden. The results demonstrated interaction effects between treatment and sampling time on the average daily gain (ADG; P=0.0005), FEC (P<0.0001), PCV (P=0.0005), and concentrations of serum amyloid A (SAA), haptoglobin (Hp), lipopolysaccharide binding protein (LBP), and α1-acid glycoprotein (α1AGP) (P<0.0001). From days 0 to 56, the ADG values for all infected lambs were lower than that of uninfected lambs, but the ADG values for all GTP-fed lambs were higher than that of INFGTP0 lambs, especially from days 28 to 42. The FECs of all GTP-fed lambs were higher than those of uninfected lambs but lower than that of INFGTP0 lambs. The PCVs of all infected lambs were lower than those of uninfected lambs, but PCV increased with increasing amounts of GTP supplementation. Furthermore, supplementation with different concentrations of GTP significantly reduced the numbers of adult H. contortus, including both males and females (P<0.0001), and the H. contortus burden in INFGTP6 lambs was reduced to uninfected levels. Overall, the SAA, Hp, LBP, and α1AGP concentrations of all infected lambs were higher than those of uninfected lambs from days 0 to 56. Two peaks in expression were observed

  9. Effects of supplementation with dietary green tea polyphenols on parasite resistance and acute phase protein response to Haemonchus contortus infection in lambs.

    PubMed

    Zhong, Rong Zhen; Li, Hao Yang; Sun, Hai Xia; Zhou, Dao Wei

    2014-09-15

    The objective of this study was to determine the effects of supplementation with dietary green tea polyphenols (GTPs) on parasite resistance and acute phase protein (APP) response to Haemonchus contortus infection in lambs. Thirty male Ujumqin lambs were randomly assigned to five treatment groups for an 8-week feeding period. Treatments included: (1) uninfected as control, (2) infected but not given GTP (INFGTP0) and (3)-(5) infected and fed 2, 4, or 6g GTP/kg feed (dry matter basis; INFGTP2, INFGTP4, and INFGTP6, respectively). Fecal and blood samples were collected to determine fecal egg count (FEC), packed cell volume (PCV), and APP concentrations. Live weight was measured once every 2 weeks. At the end of the feeding period, lambs were slaughtered to determine the adult H. contortus burden. The results demonstrated interaction effects between treatment and sampling time on the average daily gain (ADG; P=0.0005), FEC (P<0.0001), PCV (P=0.0005), and concentrations of serum amyloid A (SAA), haptoglobin (Hp), lipopolysaccharide binding protein (LBP), and α1-acid glycoprotein (α1AGP) (P<0.0001). From days 0 to 56, the ADG values for all infected lambs were lower than that of uninfected lambs, but the ADG values for all GTP-fed lambs were higher than that of INFGTP0 lambs, especially from days 28 to 42. The FECs of all GTP-fed lambs were higher than those of uninfected lambs but lower than that of INFGTP0 lambs. The PCVs of all infected lambs were lower than those of uninfected lambs, but PCV increased with increasing amounts of GTP supplementation. Furthermore, supplementation with different concentrations of GTP significantly reduced the numbers of adult H. contortus, including both males and females (P<0.0001), and the H. contortus burden in INFGTP6 lambs was reduced to uninfected levels. Overall, the SAA, Hp, LBP, and α1AGP concentrations of all infected lambs were higher than those of uninfected lambs from days 0 to 56. Two peaks in expression were observed

  10. Acute-phase response protein serum amyloid A stimulates renal tubule formation: studies in vitro and in vivo.

    PubMed

    Kelly, Katherine J; Kluve-Beckerman, Barbara; Dominguez, Jesus H

    2009-06-01

    Serum amyloid A protein (SAA) surges 1,000-fold in the blood of acute-phase animals, and yet its function during these acute events remains unknown. We report herein that SAA stimulates a developmental program in cultured NRK-52E cells that culminates in differentiated and functional tubules that feature a proximal tubule phenotype. We also found strong SAA expression in states of tubule formation (in utero stage) and regeneration (recovery from ischemia-reperfusion injury). These data lend support to a novel view of a more localized renal acute-phase reaction, where renal SAA may act as a paracrine or autocrine molecule that promotes tubule formation during development and repair.

  11. Latex-protein complexes from an acute phase recombinant antigen of Toxoplasma gondii for the diagnosis of recently acquired toxoplasmosis.

    PubMed

    Peretti, Leandro E; Gonzalez, Verónica D G; Marcipar, Iván S; Gugliotta, Luis M

    2014-08-01

    The synthesis and characterization of latex-protein complexes (LPC), from the acute phase recombinant antigen P35 (P35Ag) of Toxoplasma gondii and "core-shell" carboxylated or polystyrene (PS) latexes (of different sizes and charge densities) are considered, with the aim of producing immunoagglutination reagents able to detect recently acquired toxoplasmosis. Physical adsorption (PA) and chemical coupling (CC) of P35Ag onto latex particles at different pH were investigated. Greater amounts of adsorbed protein were obtained on PS latexes than on carboxylated latexes, indicating that hydrophobic forces govern the interactions between the protein and the particle surface. In the CC experiments, the highest amount of bound protein was obtained at pH 6, near the isoelectric point of the protein (IP=6.27). At this pH, it decreased both the repulsion between particle surface and protein, and the repulsion between neighboring molecules. The LPC were characterized and the antigenicity of the P35Ag protein coupled on the particles surface was evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA). Results from ELISA showed that the P35Ag coupled to the latex particles surface was not affected during the particles sensitization by PA and CC and the produced LPC were able to recognize specific anti-P35Ag antibodies present in the acute phase of the disease.

  12. Early prognosis of survival or death after a recent stroke by blood levels of acute-phase proteins.

    PubMed

    Ionescu, D A; Haţegan, D; Jipescu, I; Steinbruch, L; Ghiţescu, M

    1991-01-01

    From 129 patients with a recent stroke 105 survived and 24 died within 3 weeks from stroke-onset. At around 40 hours after the latter, the blood-levels of the acute-phase proteins ceruloplasmin and albumin did not forecast the death of the respective patients, but, in contradistinction, the level of fibrinogen was significantly higher in those who eventually died, than in those who survived. Therefore, a higher level of fibrinogen could be a risk-factor for death after stroke.

  13. Genetic effects on acute phase protein response to the stresses of weaning and transportation in beef calves.

    PubMed

    Qiu, X; Arthington, J D; Riley, D G; Chase, C C; Phillips, W A; Coleman, S W; Olson, T A

    2007-10-01

    The objective herein was to estimate heterosis and breed effects in purebred and crossbred Romosinuano, Brahman, and Angus calves on acute phase protein response to weaning and transportation. Calves (n = 1,032) were weaned in September of 2002, 2003, and 2004 at approximately 7 mo of age. Approximately 28 d after weaning, steer calves (n = 482) were transported 1,800 km (20 h) to Oklahoma. Concentrations of 3 acute phase proteins (ceruloplasmin, fibrinogen, and haptoglobin) were measured in blood samples. Calves (steers and heifers) were sampled at weaning, and 24 and 72 h postweaning. For separate analyses, steers sent to Oklahoma were sampled before shipment, upon arrival, and 24 and 72 h after arrival. Combinations of the following fixed effects were investigated: sire breed, dam breed, sampling time, birth location, calf sex (weaning only), year, cow age, and interactions. Effects of special interest were sire breed x dam breed as an indication of breed group of calf, and the interaction of sire and dam breeds with sampling time. Weaning age and BW were investigated as linear and quadratic covariates. Sire of calf within sire breed was a random term. The correlation structure of repeated measures was determined by comparison of information criterion values for different structures within each analysis. In general, plasma acute phase protein concentrations in weaned calves increased with sampling time. Concentrations in the transported steers increased through sampling at 24 h after arrival, and were lower at 72 h. Significant estimates of heterosis were detected for Brahman-Angus haptoglobin concentrations at weaning (0.38 +/- 0.14 mg/dL x 100; 44%), and for Romosinuano-Angus fibrinogen concentrations at weaning (11.4 +/- 5.5 mg/dL; 10%) and in transported steers (22.5 +/- 8.4 mg/dL; 20%). The direct effect of Romosinuano was to increase (P <0.004) ceruloplasmin concentrations of weaned calves (4.1 +/- 0.9 mg/dL) and of transported steers (3.9 +/- 1.3 mg

  14. Lipopolysaccharide Binding Protein and sCD14 are Not Produced as Acute Phase Proteins in Cardiac Surgery

    PubMed Central

    Kudlova, Manuela; Kunes, Pavel; Kolackova, Martina; Lonsky, Vladimir; Mandak, Jiri; Andrys, Ctirad; Jankovicova, Karolina; Krejsek, Jan

    2007-01-01

    Objectives. The changes in the serum levels of lipopolysaccharide binding protein (LBP) and sCD14 during cardiac surgery were followed in this study. Design. Thirty-four patients, 17 in each group, were randomly assigned to coronary artery bypass grafting surgery performed either with (“on-pump”) or without (“off-pump”) cardiopulmonary bypass. LBP and sCD14 were evaluated by ELISA. Results. The serum levels of LBP were gradually increased from the 1st postoperative day and reached their maximum on the 3rd postoperative day in both “on-pump” and “off-pump” patients (30.33±9.96 μg/mL; 37.99±16.58 μg/mL), respectively. There were no significant differences between “on-pump” and “off-pump” patients regarding LBP. The significantly increased levels of sCD14 from the 1st up to the 7th postoperative day in both “on-pump” and “off-pump” patients were found with no significant differences between these groups. No correlations between LBP and sCD14 and IL-6, CRP and long pentraxin PTX3 levels were found. Conclusions. The levels of LBP and sCD14 are elevated in cardiac surgical patients being similar in both groups. These molecules are not produced as acute phase proteins in these patients. PMID:18288274

  15. Early weaning alters the acute phase immune response to an endotoxin challenge in beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research indicates that early weaning prior to shipment can reduce transportation-induced increases in acute phase proteins (APP), and can increase subsequent performance in the feedlot. These data suggest that the combination of weaning and transport stress may compromise the immune system...

  16. Early weaning alters the acute phase response to an endotoxin challenge in beef calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research indicates that early weaning prior to shipment can reduce transportation-induced increases in acute phase proteins (APP), and can increase subsequent performance in the feedlot. These data suggest that the combination of weaning and transport stress may compromise the immune system...

  17. Expression of complement and pentraxin proteins in acute phase response elicited by tumor photodynamic therapy: the engagement of adrenal hormones.

    PubMed

    Merchant, Soroush; Huang, Naiyan; Korbelik, Mladen

    2010-12-01

    Treatment of solid tumors by photodynamic therapy (PDT) was recently shown to trigger a strong acute phase response. Using the mouse Lewis lung carcinoma (LLC) model, the present study examined complement and pentraxin proteins as PDT-induced acute phase reactants. The results show a distinct pattern of changes in the expression of genes encoding these proteins in the tumor, as well as host liver and spleen, following PDT mediated by photosensitizer Photofrin™. These changes were influenced by glucocorticoid hormones, as evidenced by transcriptional activation of glucocorticoid receptor and the upregulation of gene encoding this receptor. The expression of gene for glucocorticoid-induced zipper (GILZ) protein, whose activity is particularly susceptible to glucocorticoid regulation, was also changed in PDT-treated tumors. A direct demonstration that tumor PDT induces glucocorticoid hormone upregulation is provided by documenting elevated levels of serum corticosterone in mice bearing PDT-treated LLC tumors. Tumor response to PDT was negatively affected by blocking glucocorticoid receptor activity, which suggests that glucocorticoid hormones have a positive impact on the therapeutic outcome with this therapy.

  18. Protein-energy malnutrition induces an aberrant acute-phase response and modifies the circadian rhythm of core temperature.

    PubMed

    Smith, Shari E; Ramos, Rafaela Andrade; Refinetti, Roberto; Farthing, Jonathan P; Paterson, Phyllis G

    2013-08-01

    Protein-energy malnutrition (PEM), present in 12%-19% of stroke patients upon hospital admission, appears to be a detrimental comorbidity factor that impairs functional outcome, but the mechanisms are not fully elucidated. Because ischemic brain injury is highly temperature-sensitive, the objectives of this study were to investigate whether PEM causes sustained changes in temperature that are associated with an inflammatory response. Activity levels were recorded as a possible explanation for the immediate elevation in temperature upon introduction to a low protein diet. Male, Sprague-Dawley rats (7 weeks old) were fed a control diet (18% protein) or a low protein diet (PEM, 2% protein) for either 7 or 28 days. Continuous core temperature recordings from bioelectrical sensor transmitters demonstrated a rapid increase in temperature amplitude, sustained over 28 days, in response to a low protein diet. Daily mean temperature rose transiently by day 2 (p = 0.01), falling to normal by day 4 (p = 0.08), after which mean temperature continually declined as malnutrition progressed. There were no alterations in activity mean (p = 0.3) or amplitude (p = 0.2) that were associated with the early rise in mean temperature. Increased serum alpha-2-macroglobulin (p < 0.001) and decreased serum albumin (p ≤ 0.005) combined with a decrease in serum alpha-1-acid glycoprotein (p < 0.001) suggest an atypical acute-phase response. In contrast, a low protein diet had no effect on the signaling pathway of the pro-inflammatory transcription factor, NFκB, in the hippocampus. In conclusion, PEM induces an aberrant and sustained acute-phase response coupled with long-lasting effects on body temperature.

  19. Acute phase proteins, C9, factor B, and lysozyme in recurrent oral ulceration and Behçet's syndrome.

    PubMed Central

    Lehner, T; Adinolfi, M

    1980-01-01

    The concentrations and sequential changes of some acute phase proteins, factor B, and lysozyme have been assayed in recurrent oral ulceration and Behçet's syndrome. C9 was elevated in both groups of patients and was the sensitive index of disease activity; however, it failed to discriminate between the three types of recurrent oral ulcers and four types of Behçet's syndrome. The level of alpha 1 acid glycoprotein and lysozyme were significantly increased predominantly in the ocular type, whereas factor B was significantly increased especially in the neurological type of Behçet's syndrome. It is suggested that the changes in the concentrations of some plasma proteins may help our understanding of tissue involvement in Behçet's syndrome, as well as in the selection of therapeutic agents in this disease. PMID:6900632

  20. Soluble amyloid precursor protein (APP) regulates transthyretin and Klotho gene expression without rescuing the essential function of APP.

    PubMed

    Li, Hongmei; Wang, Baiping; Wang, Zilai; Guo, Qinxi; Tabuchi, Katsuhiko; Hammer, Robert E; Südhof, Thomas C; Zheng, Hui

    2010-10-01

    Amyloidogenic processing of the amyloid precursor protein (APP) generates a large secreted ectodomain fragment (APPsβ), β-amyloid (Aβ) peptides, and an APP intracellular domain (AICD). Whereas Aβ is viewed as critical for Alzheimer's disease pathogenesis, the role of other APP processing products remains enigmatic. Of interest, the AICD has been implicated in transcriptional regulation, and N-terminal cleavage of APPsβ has been suggested to produce an active fragment that may mediate axonal pruning and neuronal cell death. We previously reported that mice deficient in APP and APP-like protein 2 (APLP2) exhibit early postnatal lethality and neuromuscular synapse defects, whereas mice with neuronal conditional deletion of APP and APLP2 are viable. Using transcriptional profiling, we now identify transthyretin (TTR) and Klotho as APP/APLP2-dependent genes whose expression is decreased in loss-of-function states but increased in gain-of-function states. Significantly, by creating an APP knockin allele that expresses only APPsβ protein, we demonstrate that APPsβ is not normally cleaved in vivo and is fully capable of mediating the APP-dependent regulation of TTR and Klotho gene expression. Despite being an active regulator of gene expression, APPsβ did not rescue the lethality and neuromuscular synapse defects of APP and APLP2 double-KO animals. Our studies identify TTR and Klotho as physiological targets of APP that are regulated by soluble APPsβ independent of developmental APP functions. This unexpected APP-mediated signaling pathway may play an important role in maintaining TTR and Klotho levels and their respective functions in Aβ sequestration and aging. PMID:20855613

  1. The diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in Urinary Tract Infection (UTI) in camels

    PubMed Central

    Buczinski, Sébastien

    2015-01-01

    The present study aimed to investigate the diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in urinary tract infection (UTI) in camels. We describe the clinical, bacteriological and biochemical findings in 89 camels. Blood and urine samples from diseased (n = 74) and control camels (n = 15) were submitted to laboratory investigations. The urine analysis revealed high number of RBCS and pus cells. The concentrations of serum and erythrocytic malondialdehyde (sMDA & eMDA), Haptoglobin (Hp), serum amyloid A (SAA), Ceruloplasmin (Cp), fibrinogen (Fb), albumin, globulin and interleukin 6 (IL-6) were higher in diseased camels when compared to healthy ones. Catalase, super oxide dismutase and glutathione levels were lower in diseased camels when compared with control group. Forty one of 74 camels with UTI were successfully treated. The levels of malondialdehyde, catalase, super oxide dismutase, glutathione, Hp, SAA, Fb, total protein, globulin and IL-6 were associated with the odds of treatment failure. The MDA showed a great sensitivity (Se) and specificity (Sp) in predicting treatment failure (Se 85%/Sp 100%) as well as the SAA (Se 92%/Sp 87%) and globulin levels (Se 85%/Sp 100%) when using the cutoffs that maximizes the sum of Se + Sp. Multivariate logistic regression analysis revealed that two models had a high accuracy to predict failure with the first model including sex, sMDA and Hp as covariates (area under the receiver operating characteristic curve (AUC) = 0.92) and a second model using sex, SAA and Hp (AUC = 0.89). Conclusively, the oxidative stress biomarkers and acute phase proteins could be used as diagnostic and prognostic biomarkers in camel UTI management. Efforts should be forced to investigate such biomarkers in other species with UTI. PMID:26587339

  2. Ferroportin-1 is a 'nuclear'-negative acute-phase protein in rat liver: a comparison with other iron-transport proteins.

    PubMed

    Naz, Naila; Malik, Ihtzaz A; Sheikh, Nadeem; Ahmad, Shakil; Khan, Sajjad; Blaschke, Martina; Schultze, Frank; Ramadori, Giuliano

    2012-06-01

    Liver is the central organ of iron metabolism. During acute-phase-response (APR), serum iron concentration rapidly decreases. The current study aimed to compare expression and localization of iron transport protein ferroportin-1 (Fpn-1) and of other iron import proteins after experimental tissue damage induced by injecting turpentine oil in the hind limbs of rats and mice. Serum and spleen iron concentration decreased with an increase in total liver, cytoplasmic and nuclear iron concentration. In liver, mRNA amount of Fpn-1, Fpn-1a, Fpn-1b, HFE, hemojuvelin (HJV) and hephaestin (heph) genes showed a rapid decrease. Hepcidin, divalent metal transporter-1 (DMT-1), transferrin (Tf) and Tf-receptor-1 (TfR1), TfR-2 (TfR2) gene expression was increased. Western blot analysis of liver tissue lysate confirmed the changes observed at mRNA level. In spleen, a rapid decrease in gene expression of Fpn-1, Fpn-1a, Fpn-1b, DMT-1, Tf, TfR1 and TfR2, and an increase in hepcidin was observed. Immunohistochemistry of DMT-1 and TfR2 were mainly detected in the nucleus of rat liver and spleen, whereas TfR1 was clearly localized in the plasma membrane. Fpn-1 was mostly found in the nuclei of liver cells, whereas in spleen, the protein was mainly detected in the cell membrane. Western blot analysis of liver fractions confirmed immunohistochemical results. In livers of wild-type mice, gene expression of Fpn-1, Fpn-1a and Fpn-1b was downregulated, whereas hepcidin gene expression was increased. In contrast, these changes were less pronounced in IL-6ko-mice. Cytokine (IL-6, IL-1b and TNF-a) treatment of rat hepatocytes showed a downregulation of Fpn-1, Fpn-1a and Fpn-1b, and upregulation of hepcidin gene expression. Moreover, western blot analysis of cell lysate of IL-6-treated hepatocytes detected, as expected, an increase of a2-macroglobulin (positive acute-phase protein), whereas albumin (negative acute-phase protein) and Fpn-1 were downregulated. Our results demonstrate that liver

  3. Amyloid Precursor Protein (APP) Metabolites APP Intracellular Fragment (AICD), Aβ42, and Tau in Nuclear Roles*

    PubMed Central

    Multhaup, Gerhard; Huber, Otmar; Buée, Luc; Galas, Marie-Christine

    2015-01-01

    Amyloid precursor protein (APP) metabolites (amyloid-β (Aβ) peptides) and Tau are the main components of senile plaques and neurofibrillary tangles, the two histopathological hallmarks of Alzheimer disease. Consequently, intense research has focused upon deciphering their physiological roles to understand their altered state in Alzheimer disease pathophysiology. Recently, the impact of APP metabolites (APP intracellular fragment (AICD) and Aβ) and Tau on the nucleus has emerged as an important, new topic. Here we discuss (i) how AICD, Aβ, and Tau reach the nucleus and how AICD and Aβ control protein expression at the transcriptional level, (ii) post-translational modifications of AICD, Aβ, and Tau, and (iii) what these three molecules have in common. PMID:26296890

  4. Secreted glypican binds to the amyloid precursor protein of Alzheimer's disease (APP) and inhibits APP-induced neurite outgrowth.

    PubMed

    Williamson, T G; Mok, S S; Henry, A; Cappai, R; Lander, A D; Nurcombe, V; Beyreuther, K; Masters, C L; Small, D H

    1996-12-01

    The amyloid precursor protein (APP) of Alzheimer's disease has been shown to stimulate neurite outgrowth in vitro. The effect of APP on neurite outgrowth can be enhanced if APP is presented to neurons in substrate-bound form, in the presence of heparan sulfate proteoglycans. To identify specific heparan sulfate proteoglycans that bind to APP, conditioned medium from neonatal mouse brain cells was subjected to affinity chromatography with recombinant APP695 as a ligand. Glypican bound strongly to the APP affinity column. Purified glypican bound to APP with an equilibrium dissociation constant of 2.8 nM and inhibited APP-induced neurite outgrowth from chick sympathetic neurons. The effect of glypican was specific for APP, as glypican did not inhibit laminin-induced neurite outgrowth. Furthermore, treatment of cultures with 4-methylumbelliferyl-beta-D-xyloside, a competitive inhibitor of proteoglycan glycanation, inhibited APP-induced neurite outgrowth but did not inhibit laminin-induced neurite outgrowth. This result suggests that endogenous proteoglycans are required for substrate-bound APP to stimulate neurite outgrowth. Secreted glypican may act to inhibit APP-induced neurite outgrowth in vivo by competing with endogenous proteoglycans for binding to APP.

  5. Individuals with hematological malignancies before undergoing chemotherapy present oxidative stress parameters and acute phase proteins correlated with nutritional status.

    PubMed

    Camargo, Carolina de Quadros; Borges, Dayanne da Silva; de Oliveira, Paula Fernanda; Chagas, Thayz Rodrigues; Del Moral, Joanita Angela Gonzaga; Durigon, Giovanna Steffanello; Dias, Bruno Vieira; Vieira, André Guedes; Gaspareto, Patrick; Trindade, Erasmo Benício Santos de Moraes; Nunes, Everson Araújo

    2015-01-01

    Hematological malignancies present abnormal blood cells that may have altered functions. This study aimed to evaluate nutritional status, acute phase proteins, parameters of cell's functionality, and oxidative stress of patients with hematological malignancies, providing a representation of these variables at diagnosis, comparisons between leukemias and lymphomas and establishing correlations. Nutritional status, C-reactive protein (CRP), albumin, phagocytic capacity and superoxide anion production of mononuclear cells, lipid peroxidation and catalase activity in plasma were evaluated in 16 untreated subjects. Main diagnosis was acute leukemia (n = 9) and median body mass index (BMI) indicated overweight (25.6 kg/m(2)). Median albumin was below (3.2 g/dL) and CRP above (37.45 mg/L) the reference values. Albumin was inversely correlated with BMI (r = -0.53). Most patients were overweight before the beginning of treatment and had a high CRP/albumin ratio, which may indicate a nutrition inflammatory risk. BMI values correlated positively with lipid peroxidation and catalase activity. A strong correlation between catalase activity and lipid peroxidation was found (r = 0.75). Besides the elevated BMI, these patients also have elevated CRP values and unexpected relations between nutritional status and albumin, reinforcing the need for nutritional counseling during the course of chemotherapy, especially considering the correlations between oxidative stress parameters and nutritional status evidenced here.

  6. Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns.

    PubMed

    Chandran, Preethi K; Kuttan, Ramadasan

    2008-09-01

    Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins-haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury.

  7. The Acute-Phase Protein Orosomucoid Regulates Food Intake and Energy Homeostasis via Leptin Receptor Signaling Pathway.

    PubMed

    Sun, Yang; Yang, Yili; Qin, Zhen; Cai, Jinya; Guo, Xiuming; Tang, Yun; Wan, Jingjing; Su, Ding-Feng; Liu, Xia

    2016-06-01

    The acute-phase protein orosomucoid (ORM) exhibits a variety of activities in vitro and in vivo, notably modulation of immunity and transportation of drugs. We found in this study that mice lacking ORM1 displayed aberrant energy homeostasis characterized by increased body weight and fat mass. Further investigation found that ORM, predominantly ORM1, is significantly elevated in sera, liver, and adipose tissues from the mice with high-fat diet (HFD)-induced obesity and db/db mice that develop obesity spontaneously due to mutation in the leptin receptor (LepR). Intravenous or intraperitoneal administration of exogenous ORM decreased food intake in C57BL/6, HFD, and leptin-deficient ob/ob mice, which was absent in db/db mice and was significantly reduced in mice with arcuate nucleus (ARC) LepR knockdown, whereas enforced expression of ORM1 in ARC significantly decreased food intake, body weight, and serum insulin level. Furthermore, we found that ORM is able to bind directly to LepR and activate the receptor-mediated JAK2-STAT3 signaling in hypothalamus tissue and GT1-7 cells, which was derived from hypothalamic tumor. These data indicated that ORM could function through LepR to regulate food intake and energy homeostasis in response to nutrition status. Modulating the expression of ORM is a novel strategy for the management of obesity and related metabolic disorders.

  8. Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43.

    PubMed

    Smith, Shari E; Figley, Sarah A; Schreyer, David J; Paterson, Phyllis G

    2014-01-01

    Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia. In contrast, the effects of PEM developing in the post-ischemic period have not been studied. Since excessive inflammation can impede brain remodeling, we investigated the effects of post-ischemic malnutrition on neuroinflammation, the acute-phase reaction, and neuroplasticity-related proteins. Male, Sprague-Dawley rats were exposed to global forebrain ischemia using the 2-vessel occlusion model or sham surgery. The sham rats were assigned to control diet (18% protein) on day 3 after surgery, whereas the rats exposed to global ischemia were assigned to either control diet or a low protein (PEM, 2% protein) diet. Post-ischemic PEM decreased growth associated protein-43, synaptophysin and synaptosomal-associated protein-25 immunofluorescence within the hippocampal CA3 mossy fiber terminals on day 21, whereas the glial response in the hippocampal CA1 and CA3 subregions was unaltered by PEM. No systemic acute-phase reaction attributable to global ischemia was detected in control diet-fed rats, as reflected by serum concentrations of alpha-2-macroglobulin, alpha-1-acid glycoprotein, haptoglobin, and albumin. Acute exposure to the PEM regimen after global brain ischemia caused an atypical acute-phase response. PEM decreased the serum concentrations of albumin and haptoglobin on day 5, with the decreases sustained to day 21. Serum alpha-2-macroglobulin concentrations were significantly higher in malnourished rats on day 21. This provides the first direct evidence that PEM developing after brain ischemia exerts wide-ranging effects on mechanisms important to stroke recovery.

  9. Characterization of acute phase proteins and oxidative stress response to road transportation in the dog.

    PubMed

    Fazio, Francesco; Casella, Stefania; Giannetto, Claudia; Giudice, Elisabetta; Piccione, Giuseppe

    2015-01-01

    Haptoglobin (Hp), serum amyloid A (SAA), C-reactive protein (CRP), white blood cells (WBC), reactive oxygen metabolites (ROMs), the antioxidant barrier (Oxy-adsorbent) and thiol groups of plasma compounds (SHp) were measured in ten dogs that had been transported a distance of about 230 km within 2 h (experimental group) and in ten dogs that had not been subjected to road transportation (control group). Blood was collected via cephalic venipuncture before road transportation (T0), after road transportation (T1), and more than 6 (T6) and 24 (T24) hours after road transportation in the experimental group (Group A) and at the same time points in the control group (Group B). The GLM (general linear model) Repeated Measures procedure showed a significant difference between the two groups (P<0.0001) and a significant rise (P<0.0001) in the concentrations of Hp, SAA, CRP, WBC, ROMs, Oxy-adsorbent and SHp after road transportation in Group A, underlining that physiological and homeostatic mechanisms are modified differently at various sampling times.

  10. Relationship between cortisol and acute phase protein concentrations in female rabbits.

    PubMed

    Argente, María-José; García, María de la Luz; Birlanga, Virginia; Muelas, Raquel

    2014-10-01

    Rabbit meat production in Europe is usually based on a semi-intensive system, in which lactation and gestation overlap. The demands of lactation and pregnancy are likely to be relatively stressful for female rabbits and may compromise the immune system and reproductive performance. The present study was designed to characterise circulating levels of cortisol, haptoglobin (Hp), C-reactive protein (CRP), and serum amyloid A (SAA) in non-lactating and lactating female rabbits at first and second mating, and to determine whether any relationship exists between these biomarkers and litter size. Serum cortisol concentrations were at their greatest (mean ± SEM = 39.5 ± 3.9 nmol/L) in animals at the end of lactation. However, after weaning, cortisol concentrations were not significantly different compared to nulliparous females (19.9 ± 3.6 vs. 16.3 ± 2.2 nmol/L, respectively). The highest concentrations of circulating Hp (0.14 ± 0.01 g/L) were seen in early lactating primiparous females, and lower in nulliparous females and in rabbits after weaning. In contrast, nulliparous female rabbits showed the highest plasma CRP values (13.1 ± 1.1 mg/L). No significant differences were found for SAA. Nulliparous females had smaller litter sizes than early lactating and non-lactating primiparous female rabbits. CRP and SAA showed a positive correlation (r = +0.24, P = 0.011) and were negatively related to litter size (r = -0.23, P = 0.017 and P = 0.032, respectively). Cortisol and Hp were not related to CRP, SAA, nor to litter size. These results suggest a closer association between the mechanisms that regulate release of CRP and SAA, compared to those that regulate Hp production. Thus, lactation is associated with changes in several stress biomarkers. CRP and SAA might be more useful for evaluating animal welfare and for predicting subsequent reproductive performance of female rabbits.

  11. Alterations in oxidant/antioxidant balance, high-mobility group box 1 protein and acute phase response in cross-bred suckling piglets suffering from rotaviral enteritis.

    PubMed

    Kumar De, Ujjwal; Mukherjee, Reena; Nandi, Sukdeb; Patel, Bhimnere Hanumatnagouda Manjunatha; Dimri, Umesh; Ravishankar, Chintu; Verma, Ashok Kumar

    2014-10-01

    Rotaviral enteritis has emerged as a major cause of morbidity and mortality in piglets during their post-natal life. The present study was carried out to examine high-mobility group box 1 (HMGB1) protein, acute phase response and oxidative stress indices in the serum of suckling piglets suffering from enteritis with or without association of porcine group A rotavirus infection. The present investigation utilized 23 clinical cases with signs of acute enteritis and 12 more healthy piglets of a similar age group as control animals. Out of 23 enteritis cases, 12 cases were found to be positive for porcine group A rotavirus infection as confirmed by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers for group A rotavirus, and the rest were found negative. The acute enteritis cases in piglets were associated with an elevated level of HMGB1 protein and serum haptoglobin and ceruloplasmin suggestive of an acute phase response. Among the oxidative stress indices, the concentrations of malondialdehyde (MDA) and nitric oxide (NO) in serum were significantly increased. A pronounced drop of total antioxidant capacity and the activity of antioxidant enzymes such as catalase and superoxide dismutase in the serum of piglets suffering from acute enteritis compared to healthy ones were also noticed. The alterations in HMGB1 protein, acute phase response and oxidative stress indices were more pronounced in cases with the involvement of porcine rotavirus as compared to rotavirus-negative cases. It is concluded that HMGB1 protein, markers of oxidative stress and acute phase proteins might play an important role in the aetiopathogenesis of porcine diarrhoea caused by rotavirus and might be true markers in diagnosing the conditions leading to the extension of the prompt and effective therapeutic care.

  12. Proteins involved on TGF-β pathway are up-regulated during the acute phase of experimental Chagas disease.

    PubMed

    Ferreira, Roberto Rodrigues; de Souza, Elen Mello; de Oliveira, Fabiane Loiola; Ferrão, Patrícia Mello; Gomes, Leonardo Henrique Ferreira; Mendonça-Lima, Leila; Meuser-Batista, Marcelo; Bailly, Sabine; Feige, Jean Jacques; de Araujo-Jorge, Tania Cremonini; Waghabi, Mariana Caldas

    2016-05-01

    Studies developed by our group in the last years have shown the involvement of TGF-β in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-β cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-β is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-β signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi-infected animals presented increased expression of TGF-β receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-β. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-β activity in the heart, we found that serum levels of total TGF-β were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-β pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection.

  13. Radiometric ligand binding assay for C-reactive protein. Complexed C-reactive protein is not detectable in acute phase serum.

    PubMed

    De Beer, F C; Shine, B; Pepys, M B

    1982-10-01

    A radiometric ligand binding assay for human C-reactive protein (CRP) was established using pneumococcal C polysaccharide (CPS) coupled to magnetizable cellulose particles as the solid phase ligand. Competition for binding to the solid phase between 125I-CRP and unlabelled CRP permitted detection of 30 micrograms/l of CRP and the precise assay of concentrations up to 3000 micrograms/l. Identical results were obtained when the assay was used to quantitate isolated pure CRP and pure CRP added to normal human serum. However in vitro addition of known ligands for CRP to acute phase serum resulted in lowering of the apparent CRP concentration in this assay and addition of as little as 1 microgram/l of free CPS or 1 mg/l of lecithin was demonstrable in this way. A combination of the ligand binding assay and the standard electroimmunoassay for CRP was therefore used to test acute phase sera for the presence of CRP complexed in vitro. No evidence of complexed CRP was detected among sera containing between 1-319 mg/l of CRP from patients with Hodgkin's disease (10), rheumatoid arthritis (10), Crohn's disease (19) and various microbial infections (11), including six with subacute bacterial endocarditis. Since it is likely that CRP does form complexes with its ligands in the plasma these results suggest that complexed CRP is rapidly cleared from the circulation.

  14. Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

    PubMed

    Joe, Bina; Nagaraju, Anitha; Gowda, Lalitha R; Basrur, Venkatesha; Lokesh, Belur R

    2014-01-01

    Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I. PMID:25299597

  15. Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 1. High abundance proteins, acute phase proteins and peptidomics† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6mb00239k Click here for additional data file.

    PubMed Central

    Thomas, Funmilola Clara; Mullen, William; Tassi, Riccardo; Ramírez-Torres, Adela; Mudaliar, Manikhandan; McNeilly, Tom N.; Zadoks, Ruth N.; Burchmore, Richard

    2016-01-01

    A peptidomic investigation of milk from an experimental model of Streptococcus uberis mastitis in dairy cows has incorporated a study of milk high abundance and acute phase (APP) proteins as well as analysis of low molecular weight peptide biomarkers. Intramammary infection (IMI) with S. uberis caused a shift in abundance from caseins, β-lactoglobulin and α-lactalbumin to albumin, lactoferrin and IgG with the increase in lactoferrin occurring last. The APP response of haptoglobin, mammary associated serum amyloid A3 and C-reactive protein occurred between 30–48 hours post challenge with peak concentrations of APPs at 72–96 hours post challenge and declined thereafter at a rate resembling the fall in bacterial count rather than the somatic cell count. A peptide biomarker panel for IMI based on capillary electrophoresis and mass spectrometry was developed. It comprised 77 identified peptides (IMI77) composed mainly of casein derived peptides but also including peptides of glycosylation dependent cell adhesion molecule and serum amyloid A. The panel had a biomarker classification score that increased from 36 hour to 81 hour post challenge, significantly differentiating infected from non-infected milk, thus suggesting potential as a peptide biomarker panel of bovine mastitis and specifically that of S. uberis origin. The use of omic technology has shown a multifactorial cross system reaction in high and low abundance proteins and their peptide derivatives with changes of over a thousand fold in analyte levels in response to S. uberis infection. PMID:27412456

  16. APP independent and dependent effects on neurite outgrowth are modulated by the receptor associated protein (RAP).

    PubMed

    Billnitzer, Andrew J; Barskaya, Irina; Yin, Cailing; Perez, Ruth G

    2013-01-01

    Amyloid precursor protein (APP) and its secreted form, sAPP, contribute to the development of neurons in hippocampus, a brain region critical for learning and memory. Full-length APP binds the low-density lipoprotein receptor-related protein (LRP), which stimulates APP endocytosis. LRP also contributes to neurite growth. Furthermore, the receptor associated protein (RAP) binds LRP in a manner that blocks APP-LRP interactions. To elucidate APP contributions to neurite growth for full-length APP and sAPP, we cultured wild type (WT) and APP knockout (KO) neurons in sAPPα and/or RAP and measured neurite outgrowth at 1 day in vitro. Our data reveal that WT neurons had less axonal outgrowth including less axon branching. RAP treatment potentiated the inhibitory effects of APP. KO neurons had significantly more outgrowth and branching, especially in response to RAP, effects which were also associated with ERK2 activation. Our results affirm a major inhibitory role by full-length APP on all aspects of axonal and dendritic outgrowth, and show that RAP-LRP binding stimulated axon growth independently of APP. These findings support a major role for APP as an inhibitor of neurite growth and reveal novel signaling functions for LRP that may be disrupted by Alzheimer's pathology or therapies aimed at APP processing.

  17. Biochemical isolation of Argonaute protein complexes by Ago-APP

    PubMed Central

    Hauptmann, Judith; Schraivogel, Daniel; Bruckmann, Astrid; Manickavel, Sudhir; Jakob, Leonhard; Eichner, Norbert; Pfaff, Janina; Urban, Marc; Sprunck, Stefanie; Hafner, Markus; Tuschl, Thomas; Deutzmann, Rainer; Meister, Gunter

    2015-01-01

    During microRNA (miRNA)-guided gene silencing, Argonaute (Ago) proteins interact with a member of the TNRC6/GW protein family. Here we used a short GW protein-derived peptide fused to GST and demonstrate that it binds to Ago proteins with high affinity. This allows for the simultaneous isolation of all Ago protein complexes expressed in diverse species to identify associated proteins, small RNAs, or target mRNAs. We refer to our method as “Ago protein Affinity Purification by Peptides“ (Ago-APP). Furthermore, expression of this peptide competes for endogenous TNRC6 proteins, leading to global inhibition of miRNA function in mammalian cells. PMID:26351695

  18. Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons.

    PubMed

    Niessen, R W; Lamping, R J; Jansen, P M; Prins, M H; Peters, M; Taylor, F B; de Vijlder, J J; ten Cate, J W; Hack, C E; Sturk, A

    1997-09-01

    Patients with sepsis or after major surgery have decreased plasma levels of the anticoagulant protein antithrombin. In such patients elevated levels of interleukin-6 (IL-6) are present and this interleukin is known to induce positive and negative acute phase responses. To investigate the possibility that antithrombin acts as a negative acute phase response-protein we performed studies on the human hepatoma cell line HepG2 in vitro and baboons in vivo. HepG2 cells were treated with recombinant human IL-6, IL-1beta, or combinations of the latter two, and tested for production of antithrombin, fibrinogen and prealbumin (transthyretin). This treatment resulted in a dose dependent increase in fibrinogen concentration (with a maximum effect of 2.8-2.9-fold) and a dose dependent decrease in prealbumin (with a maximum effect of 0.6-0.7-fold) and antithrombin concentrations (with a maximum effect of 0.6-0.8-fold). Simultaneous treatment of the HepG2 cells with IL-6 (1,000 pg/ml or 2,500 pg/ml) and IL-1beta (25 pg/ml), provided more extensively decreased prealbumin (0.8 and 0.6-fold, respectively) and antithrombin concentration (0.7 and 0.6-fold, respectively) compared to the single interleukin treatment at these concentrations. Baboons treated with 2 microg IL-6 x kg body-weight(-1) x day(-1) showed increased plasma CRP levels (59-fold, p <0.05) and decreased prealbumin (0.9-fold, p <0.05) and antithrombin (0.8-fold, p <0.05) plasma levels, without evidence for coagulation activation. Our results indicate that antithrombin acts as a negative acute phase protein, which may contribute to the decreased antithrombin plasma levels observed after major surgery or in sepsis.

  19. Reduction of liver function delays resumption of postpartum ovarian activity and alters the synthesis of acute phase proteins in dairy cows.

    PubMed

    Montagner, Paula; Krause, Ana Rita Tavares; Schwegler, Elizabeth; Weschenfelder, Marina Menoncin; Rabassa, Viviane Rohrig; Schneider, Augusto; Pereira, Rubens Alves; Brauner, Cássio Cassal; Del Pino, Francisco Augusto Burkert; Gonçalves, Fernanda Medeiros; Corrêa, Marcio Nunes

    2016-06-01

    The aim of this study was to evaluate the concentration of acute phase proteins, milk production, and resumption of postpartum ovarian activity of clinically healthy dairy cows in a semi-extensive system with different Liver Functionality Index (LFI) values. The animals were divided into two groups: Low LFI (LLFI: -7 to -12; n: 10) and High LFI (HLFI: -7 to -4; n: 10). Animals with LLFI had lower paraoxonase activity and lower albumin concentration in the pre- and postpartum periods (P<0.05), higher non-esterified fatty acids prepartum (P<0.005), and higher haptoglobin concentration postpartum (P<0.01). The LLFI group showed lower resumption of ovarian activity until 44days postpartum (29%; P<0.05) than HLFI (86%). Milk production did not differ between groups. Therefore, this study suggests that the LFI is an important biomarker of synthesis of acute phase proteins and the first ovulation interval, and it can be used to improve the production and reproductive performance. PMID:27234541

  20. High Fat Diet Enhances β-Site Cleavage of Amyloid Precursor Protein (APP) via Promoting β-Site APP Cleaving Enzyme 1/Adaptor Protein 2/Clathrin Complex Formation.

    PubMed

    Maesako, Masato; Uemura, Maiko; Tashiro, Yoshitaka; Sasaki, Kazuki; Watanabe, Kiwamu; Noda, Yasuha; Ueda, Karin; Asada-Utsugi, Megumi; Kubota, Masakazu; Okawa, Katsuya; Ihara, Masafumi; Shimohama, Shun; Uemura, Kengo; Kinoshita, Ayae

    2015-01-01

    Obesity and type 2 diabetes are risk factors of Alzheimer's disease (AD). We reported that a high fat diet (HFD) promotes amyloid precursor protein (APP) cleavage by β-site APP cleaving enzyme 1 (BACE1) without increasing BACE1 levels in APP transgenic mice. However, the detailed mechanism had remained unclear. Here we demonstrate that HFD promotes BACE1/Adaptor protein-2 (AP-2)/clathrin complex formation by increasing AP-2 levels in APP transgenic mice. In Swedish APP overexpressing Chinese hamster ovary (CHO) cells as well as in SH-SY5Y cells, overexpression of AP-2 promoted the formation of BACE1/AP-2/clathrin complex, increasing the level of the soluble form of APP β (sAPPβ). On the other hand, mutant D495R BACE1, which inhibits formation of this trimeric complex, was shown to decrease the level of sAPPβ. Overexpression of AP-2 promoted the internalization of BACE1 from the cell surface, thus reducing the cell surface BACE1 level. As such, we concluded that HFD may induce the formation of the BACE1/AP-2/clathrin complex, which is followed by its transport of BACE1 from the cell surface to the intracellular compartments. These events might be associated with the enhancement of β-site cleavage of APP in APP transgenic mice. Here we present evidence that HFD, by regulation of subcellular trafficking of BACE1, promotes APP cleavage. PMID:26414661

  1. The application of Artocarpus integer seed lectin-M in the detection and isolation of selective human serum acute-phase proteins and immunoglobulins.

    PubMed

    Hashim, O H; Ahmad, F; Shuib, A S

    2001-05-01

    Champedak (Artocarpus integer) lectin-M is a lectin with high specificity and affinity for the core-mannosyl residues of the N-linked oligosaccharides of glycoproteins. We have studied the interaction of the champedak seed lectin with human serum glycoproteins that were resolved by 2-dimensional (2-D) gel electrophoresis. The lectin demonstrated strong interaction with haptoglobin beta chain, orosomucoid, alpha1-antitrypsin, alpha2-HS glycoprotein, transferrin, hemopexin, alpha1B-glycoprotein, and the heavy chains of IgA, IgM and IgG of the human serum. With exceptions of the heavy chains of the immunoglobulins and alpha1B-glycoprotein, all the other lectin-M-probed glycopeptides are acute-phase proteins. The use of champedak lectin-M to probe for serum glycoproteins that were separated in a 2-D gel electrophoresis and Western blotting technique may be conveniently applied to analyse the acute-phase and humoral immune responses simultaneously. Subjecting human serum to immobilised-lectin-M affinity chromatography was able to isolate intact haptoglobin, alpha1-antitrypsin, alpha1B-glycoprotein, hemopexin and IgA.

  2. Comparative study of Helicobacter pylori infection in guinea pigs and mice - elevation of acute-phase protein C3 in infected guinea pigs.

    PubMed

    Sjunnesson, H; Sturegård, E; Grubb, A; Willén, R; Wadström, T

    2001-03-01

    Eighteen Dunkin-Hartley guinea pigs and 50 NMRI mice were inoculated with Helicobacter pylori and the infection followed by culture, histopathology, antibody response, and plasma levels of the acute-phase proteins albumin, C3, and transferrin for up to 7 weeks. The immune response to H. pylori surface proteins was studied by an enzyme immunoassay (EIA) and Western immunoblot and the plasma levels of albumin, C3, and transferrin were analyzed by single radial immunodiffusion. Guinea pigs had a more severe gastritis and a higher EIA immune response than NMRI mice. Serum C3 levels were elevated in infected guinea pigs after 3 and 7 weeks indicating a systemic inflammatory response and a possible link between H. pylori infection and extragastric manifestations such as vasculitis associated with atherosclerosis. Serum cholesterol levels were analyzed in guinea pigs at 7 weeks and indicated a higher level in H. pylori-infected than in control animals, but this difference was not statistically significant.

  3. Undernutrition, the Acute Phase Response to Infection, and Its Effects on Micronutrient Status Indicators12

    PubMed Central

    Bresnahan, Kara A.; Tanumihardjo, Sherry A.

    2014-01-01

    Infection and undernutrition are prevalent in developing countries and demonstrate a synergistic relation. Undernutrition increases infection-related morbidity and mortality. The acute phase response (APR) is an innate, systemic inflammatory reaction to a wide array of disruptions in a host’s homeostasis, including infection. Released from immune cells in response to deleterious stimuli, proinflammatory cytokines act on distant tissues to induce behavioral (e.g., anorexia, weakness, and fatigue) and systemic effects of the APR. Cytokines act to increase energy and protein requirements to manifest fever and support hepatic acute phase protein (APP) production. Blood concentrations of glucose and lipid are augmented to provide energy to immune cells in response to cytokines. Additionally, infection decreases intestinal absorption of nutrients and can cause direct loss of micronutrients. Traditional indicators of iron, zinc, and vitamin A status are altered during the APR, leading to inaccurate estimations of deficiency in populations with a high or unknown prevalence of infection. Blood concentrations of APPs can be measured in nutrition interventions to assess the time stage and severity of infection and correct for the APR; however, standardized cutoffs for nutrition applications are needed. Protein-energy malnutrition leads to increased gut permeability to pathogens, abnormal immune cell populations, and impaired APP response. Micronutrient deficiencies cause specific immune impairments that affect both innate and adaptive responses. This review describes the antagonistic interaction between the APR and nutritional status and emphasizes the need for integrated interventions to address undernutrition and to reduce disease burden in developing countries. PMID:25398733

  4. Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns

    PubMed Central

    Chandran, Preethi K.; Kuttan, Ramadasan

    2008-01-01

    Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins—haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury. PMID:18818737

  5. Tail biting induces a strong acute phase response and tail-end inflammation in finishing pigs.

    PubMed

    Heinonen, Mari; Orro, Toomas; Kokkonen, Teija; Munsterhjelm, Camilla; Peltoniemi, Olli; Valros, Anna

    2010-06-01

    The extent of inflammation associated with tail biting in finishing pigs was evaluated. Tail histopathology, carcass condemnation and the concentration of three acute phase proteins (APPs), C-reactive protein (CRP), serum amyloid-A (SAA) and haptoglobin (Hp), were examined in 12 tail-bitten and 13 control pigs. The median concentrations of APPs were higher (P<0.01) in bitten (CRP 617.5mg/L, range 80.5-969.9; SAA 128.0mg/L, 6.2-774.4; Hp 2.8g/L, 1.6-3.5) than in control pigs (CRP 65.7mg/L, 28.4-180.4; SAA 6.2mg/L, 6.2-21.4; Hp 1.2g/L, 0.9-1.5). There was a tendency for APP concentrations to rise with the histopathological score but the differences were only statistically significant between some of the scores. Five (42%) bitten cases and one (8%) control pig had partial carcass condemnations owing to abscesses (P=0.07). The results show that tail biting induces an inflammatory response in the tail end leading to an acute phase response and formation of carcass abscesses. PMID:19398209

  6. Mint proteins are required for synaptic activity-dependent amyloid precursor protein (APP) trafficking and amyloid β generation.

    PubMed

    Sullivan, Sarah E; Dillon, Gregory M; Sullivan, Josefa M; Ho, Angela

    2014-05-30

    Aberrant amyloid β (Aβ) production plays a causal role in Alzheimer disease pathogenesis. A major cellular pathway for Aβ generation is the activity-dependent endocytosis and proteolytic cleavage of the amyloid precursor protein (APP). However, the molecules controlling activity-dependent APP trafficking in neurons are less defined. Mints are adaptor proteins that directly interact with the endocytic sorting motif of APP and are functionally important in regulating APP endocytosis and Aβ production. We analyzed neuronal cultures from control and Mint knockout neurons that were treated with either glutamate or tetrodotoxin to stimulate an increase or decrease in neuronal activity, respectively. We found that neuronal activation by glutamate increased APP endocytosis, followed by elevated APP insertion into the cell surface, stabilizing APP at the plasma membrane. Conversely, suppression of neuronal activity by tetrodotoxin decreased APP endocytosis and insertion. Interestingly, we found that activity-dependent APP trafficking and Aβ generation were blocked in Mint knockout neurons. We showed that wild-type Mint1 can rescue APP internalization and insertion in Mint knockout neurons. In addition, we found that Mint overexpression increased excitatory synaptic activity and that APP was internalized predominantly to endosomes associated with APP processing. We demonstrated that presenilin 1 (PS1) endocytosis requires interaction with the PDZ domains of Mint1 and that this interaction facilitates activity-dependent colocalization of APP and PS1. These findings demonstrate that Mints are necessary for activity-induced APP and PS1 trafficking and provide insight into the cellular fate of APP in endocytic pathways essential for Aβ production.

  7. Screening of APP interaction proteins by DUALmembrane yeast two-hybrid system

    PubMed Central

    Yu, You; Li, Yinan; Zhang, Yan

    2015-01-01

    Alzheimer’s disease (AD) is one of the most common forms of neurodegenerative disease. There is a growing interest in the amyloid precursor protein (APP) over the years due to its involvement in AD. Besides its role in pathological mechanisms of AD, APP participates in many signaling pathways as well. APP functions through protein-protein interactions, and in this report staufen 1 (STAU1) is demonstrated to have interaction with APP, using yeast two-hybrid screening and co-immunoprecipitation in mammalian system. STAU1 belongs to the double-stranded RNA binding protein family and can mediate mRNA degradation in mammalian system, implicating that APP may be involved in the regulation of mRNA as well. PMID:26045787

  8. The acute phase response of C3, C5, ceruloplasmin, and C-reactive protein induced by turpentine pleurisy in the rabbit.

    PubMed Central

    Giclas, P. C.; Manthei, U.; Strunk, R. C.

    1985-01-01

    Concentrations of five serum proteins, C3, C5, ceruloplasmin, C-reactive protein, and albumin, have been measured during the acute phase response in rabbits with turpentine-induced pleurisy. C-reactive protein concentrations in the circulation rose abruptly between 12 and 36 hours to a level greater than 50 times the pretreatment concentration, then returned to undetectable amounts by 96 hours. C3 and ceruloplasmin both showed some increase in concentration by 12 hours and reached their maximum concentrations of two to three times the baseline levels 48-72 hours after the turpentine treatment. Concentrations were still elevated at 120 hours, after which time they gradually returned to normal. C5 and albumin concentrations in the turpentine-treated rabbits did not differ from the baseline concentrations. The same five proteins were measured in the inflammatory exudate. C-reactive protein was not detectable at any of the time points. C3, C5, ceruloplasmin, and albumin were present in normal pleural fluid at roughly half their serum concentrations. The activities of C3, C5, and ceruloplasmin were low in the early exudate, but C3 and C5 activity rose relative to their concentrations in the later samples of pleural fluid. The specific activities of C3 and C5 were higher in the pleural fluid at 72 hours than in plasma, while that of ceruloplasmin remained less in the pleural fluid than in plasma throughout the experiment. The involvement of these proteins and their relation to the inflammatory response are discussed. Images Figure 6 PMID:2409807

  9. Inflammatory cytokines and acute-phase proteins concentrations in the peripheral blood and uterus of cows that developed endometritis during early postpartum.

    PubMed

    Brodzki, P; Kostro, K; Brodzki, A; Wawron, W; Marczuk, J; Kurek, Ł

    2015-07-01

    The aim of the study was to evaluate the level of proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]), anti-inflammatory cytokine (interleukin-10 [IL-10]), and acute-phase proteins (haptoglobin [Hp] and serum amyloid A [SAA]) in serum and uterine washings in cows that developed endometritis during the early postpartum period. The study was carried out on 40 cows. The experimental group consisted of 20 cows with subclinical endometritis and the control group of 20 cows without endometritis. Analyses in both groups of cows were carried out at 5, 22, and 40 days postpartum (DPP). Experimental material consisted of the blood serum and uterine washings. The levels of the following cytokines: TNF-α, IL-6, IL-10 and acute-phase proteins: Hp and SAA were determined using ELISA. Our study reported that the levels of TNF-α, IL-6, IL-10, Hp, and SAA at 22 DPP were higher in cows with subclinical endometritis (P < 0.001). The levels of TNF-α (P = 0.01), IL-6 and IL-10 (P = 0.001), and Hp (P < 0.001) at 40 DPP were higher in cows with subclinical endometritis compared to healthy cows. The level of IL-10 in uterine washings at 5 DPP was higher (P = 0.001), whereas of SAA was lower (P = 0.01) in cows with subclinical endometritis. At 22 DPP, the levels of IL-6, IL-10, and Hp were higher (P < 0.001) in cows with endometritis. At 40 DPP, the level of TNF-α was lower, whereas these of IL-10 and Hp were elevated (P < 0.001) in cows with endometritis compared to healthy cows. The results indicate that the evaluation of the levels of cytokines and Hp in serum, but primarily in uterine washings, can be an important diagnostic indicator in cows that developed subclinical endometritis. High levels of IL-10 in cows with subclinical endometritis may contribute to the weakening of local resistance mechanisms of the uterus and lead to the persistence of the inflammation in the postpartum period. The present study also shows that the simultaneous examination

  10. Protein-DNA interactions in the promoter region of the amyloid precursor protein (APP) gene in human neocortex.

    PubMed

    Lukiw, W J; Rogaev, E I; Wong, L; Vaula, G; McLachlan, D R; St George Hyslop, P

    1994-03-01

    We have investigated protein-DNA interactions in the proximal promoter of the human amyloid precursor protein (APP) gene in temporal lobe neocortical nuclei isolated from control and Alzheimer disease (AD) affected brains. We report that the human APP 5' promoter sequence from -203 to +55 bp, which has been previously reported to contain essential regulatory elements for APP gene transcription, lies in a deoxyribonuclease I, micrococcal nuclease- and restriction endonuclease-sensitive, G+C-rich nucleosome-free gap flanked both 5' and 3' by typical nucleosome structures. As analyzed by electrophoretic mobility shift assay, this extended internucleosomal linker DNA is heavily occupied by nuclear protein factors, and interacts differentially with nuclear protein extracts obtained from HeLa and human brain neocortical nuclei. This suggests that the chromatin conformation of the APP gene promoter may vary in different cell types, and may correlate with differences in APP gene expression. Human recombinant transcription factors AP1, SP1 and TFIID (but not AP2 or brain histones H1, H2B and H4) interact with the -203 to +55 bp of the human APP promoter sequence. Only minor differences were observed in the chromatin structure of the immediate APP promoter between non-AD and AD affected neocortical nuclei, suggesting either that post-transcriptional processes, or that regulatory elements lying elsewhere in the APP gene may be important in the aberrant accumulation of the APP gene product.

  11. Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial

    PubMed Central

    2011-01-01

    Background Prolonged preoperative fasting increases insulin resistance and current evidence recommends carbohydrate (CHO) drinks 2 hours before surgery. Our hypothesis is that the addition of whey protein to a CHO-based drink not only reduces the inflammatory response but also diminish insulin resistance. Methods Seventeen patients scheduled to cholecystectomy or inguinal herniorraphy were randomized and given 474 ml and 237 ml of water (CO group) or a drink containing CHO and milk whey protein (CHO-P group) respectively, 6 and 3 hours before operation. Blood samples were collected before surgery and 24 hours afterwards for biochemical assays. The endpoints of the study were the insulin resistance (IR), the prognostic inflammatory and nutritional index (PINI) and the C-reactive protein (CRP)/albumin ratio. A 5% level for significance was established. Results There were no anesthetic or postoperative complications. The post-operative IR was lower in the CHO-P group when compared with the CO group (2.75 ± 0.72 vs 5.74 ± 1.16; p = 0.03). There was no difference between the two groups in relation to the PINI. The CHO-P group showed a decrease in the both CRP elevation and CRP/albumin ratio (p < 0.05). The proportion of patients who showed CRP/albumin ratio considered normal was significantly greater (p < 0.05) in the CHO-P group (87.5%) than in the CO group (33.3%). Conclusions Shortening the pre-operative fasting using CHO and whey protein is safe and reduces insulin resistance and postoperative acute phase response in elective moderate operations. Trial registration ClinicalTrail.gov NCT01354249 PMID:21668975

  12. Energy status, lipid-soluble vitamins, and acute phase proteins in periparturient Holstein and Jersey dairy cows with or without subclinical mastitis.

    PubMed

    Rezamand, P; Hoagland, T A; Moyes, K M; Silbart, L K; Andrew, S M

    2007-11-01

    In a retrospective, case-controlled, observational study, associations among indices of negative energy balance, plasma lipid and lipid-soluble vitamin concentrations, plasma acute phase protein status, and occurrence of a new subclinical intramammary infection (IMI) during the periparturient period were determined. Cows were paired based on breed and expected parturition date (EPD) and monitored from the cessation of lactation through wk 8 of the subsequent lactation. A cow was identified as developing a new IMI if the intramammary pathogen isolated postpartum differed from that isolated in wk -9 (relative to EPD). Mean body condition score (BCS) of cows at wk -9 was 3.71 +/- 0.12. Fifteen Holstein and 15 Jersey dairy cows met the study selection criteria. Cows with a new IMI had greater body condition score, body weight, and body weight loss compared with cows that did not develop a new IMI. Prepartum plasma concentrations of beta-carotene were greater for Jersey cows with a new IMI compared with Jersey cows without a new IMI and Holstein cows, regardless of IMI status. However, there was a significant delay in recovery of plasma concentrations of beta-carotene postpartum for Jersey cows with a new IMI compared with Jersey cows without a new IMI. Plasma alpha-tocopherol, albumin, and retinol binding protein concentrations were greater during the periparturient period for cows without a new IMI. Plasma haptoglobin was increased at wk 1 postpartum for cows without a new IMI. Milk protein and lactose percentages and milk urea N were decreased and somatic cell counts were increased in cows identified with a new IMI compared with cows that did not develop a new IMI. Dairy cows with greater tissue energy stores prepartum and reduced plasma proteins, beta-carotene, and alpha-tocopherol had a greater risk for developing a new IMI during the periparturient period.

  13. Immunomodulatory effects of high-protein diet with resveratrol supplementation on radiation-induced acute-phase inflammation in rats.

    PubMed

    Kim, Kyoung-Ok; Park, HyunJin; Chun, Mison; Kim, Hyun-Sook

    2014-09-01

    We hypothesized that a high-protein diet and/or resveratrol supplementation will improve acute inflammatory responses in rats after receiving experimental abdominal radiation treatment (ART). Based on our previous study, the period of 10 days after ART was used as an acute inflammation model. Rats were exposed to a radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At day 10 after ART, we measured profiles of lipids, proteins, and immune cells in blood. The levels of clusters of differentiating 4(+) (CD4(+)) cells and regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant disturbances of lipid profiles by increasing triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein cholesterol. The proinflammatroy cytokine levels were also increased by ART. All the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts were increased. In addition, the HP and [HP+RES] diets decreased the concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets decreased regulatory T cells compared with those of the control diet in ART group. Further, the HP diet led to a significant recovery of white blood cell counts, as well as increased percentages of lymphocyte and decreased percentages of neutrophils. In summary, RES appeared to be significantly effective in minimizing radiation-induced damage to lipid metabolism and immune responses. Our study also demonstrated the importance of dietary protein intake in recovering from acute inflammation by radiation.

  14. The acute phase protein ceruloplasmin as a non-invasive marker of pseudopregnancy, pregnancy, and pregnancy loss in the giant panda.

    PubMed

    Willis, Erin L; Kersey, David C; Durrant, Barbara S; Kouba, Andrew J

    2011-01-01

    After ovulation, non-pregnant female giant pandas experience pseudopregnancy. During pseudopregnancy, non-pregnant females exhibit physiological and behavioral changes similar to pregnancy. Monitoring hormonal patterns that are usually different in pregnant mammals are not effective at determining pregnancy status in many animals that undergo pseudopregnancy, including the giant panda. Therefore, a physiological test to distinguish between pregnancy and pseudopregnancy in pandas has eluded scientists for decades. We examined other potential markers of pregnancy and found that activity of the acute phase protein ceruloplasmin increases in urine of giant pandas in response to pregnancy. Results indicate that in term pregnancies, levels of active urinary ceruloplasmin were elevated the first week of pregnancy and remain elevated until 20-24 days prior to parturition, while no increase was observed during the luteal phase in known pseudopregnancies. Active ceruloplasmin also increased during ultrasound-confirmed lost pregnancies; however, the pattern was different compared to term pregnancies, particularly during the late luteal phase. In four out of the five additional reproductive cycles included in the current study where females were bred but no birth occurred, active ceruloplasmin in urine increased during the luteal phase. Similar to the known lost pregnancies, the temporal pattern of change in urinary ceruloplasmin during the luteal phase deviated from the term pregnancies suggesting that these cycles may have also been lost pregnancies. Among giant pandas in captivity, it has been presumed that there is a high rate of pregnancy loss and our results are the first to provide evidence supporting this notion.

  15. Ablation of C/EBP homologous protein increases the acute phase mortality and doesn't attenuate cardiac remodeling in mice with myocardial infarction.

    PubMed

    Luo, Guangjin; Li, Qingman; Zhang, Xiajun; Shen, Liang; Xie, Jiahe; Zhang, Jingwen; Kitakaze, Masafumi; Huang, Xiaobo; Liao, Yulin

    2015-08-14

    Endoplasmic reticulum stress is a proapoptotic and profibrotic stimulus. Ablation of C/EBP homologous protein (CHOP) is reported to reverse cardiac dysfunction by attenuating cardiac endoplasmic reticulum stress in mice with pressure overload or ischemia/reperfusion, but it is unclear whether loss of CHOP also inhibits cardiac remodeling induced by permanent-infarction. In mice with permanent ligation of left coronary artery, we found that ablation of CHOP increased the acute phase mortality. For the mice survived to 4 weeks, left ventricular anterior (LV) wall thickness was larger in CHOP knockout mice than in the wildtype littermates, while no difference was noted on posterior wall thickness, LV dimensions, LV fractional shortening and ejection fraction. Similarly, invasive assessment of LV hemodynamics, morphological analysis of heart and lung weight indexes, myocardial fibrosis and TUNEL-assessed apoptosis showed no significant differences between CHOP knockout mice and their wildtype ones, while in mice with ischemia for 45 min and reperfusion for 1 week, myocardial fibrosis and apoptosis in the infarct area were significantly attenuated in CHOP knockout mice. These findings indicate that ablation of CHOP doesn't ameliorate cardiac remodeling induced by permanent-myocardial infarction, which implicates that early reperfusion is a prerequisite for ischemic myocardium to benefit from CHOP inhibition.

  16. [Comparative studies on the value of acute phase proteins and CA-125 for monitoring patients with ovarian cancer].

    PubMed

    Kölbl, H; Tatra, G; Schieder, K; Bieglmayer, C

    1988-12-01

    In a study of 71 patients with malignant ovarian tumors serum levels of CA-125, C-reactive protein (CRP), alpha-1-antitrypsin and coeruloplasmin were analysed. In contrast to the tumor-free group significantly higher values of CA-125, CRP and alpha-1-antitrypsin were found in the group with recurrent disease. However, the serum-concentrations of coeruloplasmin remained unchanged in both groups. In the group with progressive disease the median values of CA-125 were greater than 65 U/ml and of CRP greater than 12 micron/ml, respectively. The median serum concentrations of alpha-1-antitrypsin (2 to 4 mg/ml) and coeruloplasmin (150 to 600 ng/ml) did not reach their cut-off levels. Beside CA-125 the analysis of CRP and alpha-1-antitrypsin is an additional helpful procedure for the monitoring of patients with malignant ovarian tumors.

  17. The Acute Phase Protein Ceruloplasmin as a Non-Invasive Marker of Pseudopregnancy, Pregnancy, and Pregnancy Loss in the Giant Panda

    PubMed Central

    Willis, Erin L.; Kersey, David C.; Durrant, Barbara S.; Kouba, Andrew J.

    2011-01-01

    After ovulation, non-pregnant female giant pandas experience pseudopregnancy. During pseudopregnancy, non-pregnant females exhibit physiological and behavioral changes similar to pregnancy. Monitoring hormonal patterns that are usually different in pregnant mammals are not effective at determining pregnancy status in many animals that undergo pseudopregnancy, including the giant panda. Therefore, a physiological test to distinguish between pregnancy and pseudopregnancy in pandas has eluded scientists for decades. We examined other potential markers of pregnancy and found that activity of the acute phase protein ceruloplasmin increases in urine of giant pandas in response to pregnancy. Results indicate that in term pregnancies, levels of active urinary ceruloplasmin were elevated the first week of pregnancy and remain elevated until 20–24 days prior to parturition, while no increase was observed during the luteal phase in known pseudopregnancies. Active ceruloplasmin also increased during ultrasound-confirmed lost pregnancies; however, the pattern was different compared to term pregnancies, particularly during the late luteal phase. In four out of the five additional reproductive cycles included in the current study where females were bred but no birth occurred, active ceruloplasmin in urine increased during the luteal phase. Similar to the known lost pregnancies, the temporal pattern of change in urinary ceruloplasmin during the luteal phase deviated from the term pregnancies suggesting that these cycles may have also been lost pregnancies. Among giant pandas in captivity, it has been presumed that there is a high rate of pregnancy loss and our results are the first to provide evidence supporting this notion. PMID:21765892

  18. Independent Relationship between Amyloid Precursor Protein (APP) Dimerization and γ-Secretase Processivity

    PubMed Central

    Jung, Joo In; Premraj, Sasha; Cruz, Pedro E.; Ladd, Thomas B.; Kwak, Yewon; Koo, Edward H.; Felsenstein, Kevin M.; Golde, Todd E.; Ran, Yong

    2014-01-01

    Altered production of β-amyloid (Aβ) from the amyloid precursor protein (APP) is closely associated with Alzheimer’s disease (AD). APP has a number of homo- and hetero-dimerizing domains, and studies have suggested that dimerization of β-secretase derived APP carboxyl terminal fragment (CTFβ, C99) impairs processive cleavage by γ-secretase increasing production of long Aβs (e.g., Aβ1-42, 43). Other studies report that APP CTFβ dimers are not γ-secretase substrates. We revisited this issue due to observations made with an artificial APP mutant referred to as 3xK-APP, which contains three lysine residues at the border of the APP ectodomain and transmembrane domain (TMD). This mutant, which dramatically increases production of long Aβ, was found to form SDS-stable APP dimers, once again suggesting a mechanistic link between dimerization and increased production of long Aβ. To further evaluate how multimerization of substrate affects both initial γ-secretase cleavage and subsequent processivity, we generated recombinant wild type- (WT) and 3xK-C100 substrates, isolated monomeric, dimeric and trimeric forms of these proteins, and evaluated both ε-cleavage site utilization and Aβ production. These show that multimerization significantly impedes γ-secretase cleavage, irrespective of substrate sequence. Further, the monomeric form of the 3xK-C100 mutant increased long Aβ production without altering the initial ε-cleavage utilization. These data confirm and extend previous studies showing that dimeric substrates are not efficient γ-secretase substrates, and demonstrate that primary sequence determinants within APP substrate alter γ-secretase processivity. PMID:25350374

  19. Interactions between Hepatitis C Virus and the Human Apolipoprotein H Acute Phase Protein: A Tool for a Sensitive Detection of the Virus.

    PubMed

    Stefas, Ilias; Tigrett, Sylvia; Dubois, Grégor; Kaiser, Marco; Lucarz, Estelle; Gobby, Delphine; Bray, Dorothy; Ellerbrok, Heinz; Zarski, Jean Pierre; Veas, Francisco

    2015-01-01

    The Hepatitis C virus (HCV) infection exhibits a high global prevalence frequently associated with hepatocellular carcinoma, taking years to develop. Despite the standardization of highly sensitive HCV quantitative RT-PCR (qRT-PCR) detection methods, false-negative diagnoses may be generated with current methods, mainly due to the presence of PCR inhibitors and/or low viral loads in the patient's sample. These false-negative diagnoses impact both public health systems, in developing countries, and an in lesser extent, in developed countries, including both the risk of virus transmission during organ transplantation and/or blood transfusion and the quality of the antiviral treatment monitoring. To adopt an appropriate therapeutic strategy to improve the patient's prognosis, it is urgent to increase the HCV detection sensitivity. Based upon previous studies on HBV, we worked on the capacity of the scavenger acute phase protein, Apolipoprotein H (ApoH) to interact with HCV. Using different approaches, including immunoassays, antibody-inhibition, oxidation, ultracentrifugation, electron microscopy and RT-PCR analyses, we demonstrated specific interactions between HCV particles and ApoH. Moreover, when using a two-step HCV detection process, including capture of HCV by ApoH-coated nanomagnetic beads and a home-made real-time HCV-RT-PCR, we confirmed the presence of HCV for all samples from a clinical collection of HCV-seropositive patients exhibiting an RT-PCR COBAS® TaqMan® HCV Test, v2.0 (COBAS)-positive result. In contrast, for HCV-seropositive patients with either low HCV-load as determined with COBAS or exhibiting HCV-negative COBAS results, the addition of the two-step ApoH-HCV-capture and HCV-detection process was able to increase the sensitivity of HCV detection or more interestingly, detect in a genotype sequence-independent manner, a high-proportion (44%) of HCV/RNA-positive among the COBAS HCV-negative patients. Thus, the immune interaction between ApoH and

  20. Interactions between Hepatitis C Virus and the Human Apolipoprotein H Acute Phase Protein: A Tool for a Sensitive Detection of the Virus

    PubMed Central

    Dubois, Grégor; Kaiser, Marco; Lucarz, Estelle; Gobby, Delphine; Bray, Dorothy; Ellerbrok, Heinz; Zarski, Jean Pierre; Veas, Francisco

    2015-01-01

    The Hepatitis C virus (HCV) infection exhibits a high global prevalence frequently associated with hepatocellular carcinoma, taking years to develop. Despite the standardization of highly sensitive HCV quantitative RT-PCR (qRT-PCR) detection methods, false-negative diagnoses may be generated with current methods, mainly due to the presence of PCR inhibitors and/or low viral loads in the patient’s sample. These false-negative diagnoses impact both public health systems, in developing countries, and an in lesser extent, in developed countries, including both the risk of virus transmission during organ transplantation and/or blood transfusion and the quality of the antiviral treatment monitoring. To adopt an appropriate therapeutic strategy to improve the patient’s prognosis, it is urgent to increase the HCV detection sensitivity. Based upon previous studies on HBV, we worked on the capacity of the scavenger acute phase protein, Apolipoprotein H (ApoH) to interact with HCV. Using different approaches, including immunoassays, antibody-inhibition, oxidation, ultracentrifugation, electron microscopy and RT-PCR analyses, we demonstrated specific interactions between HCV particles and ApoH. Moreover, when using a two-step HCV detection process, including capture of HCV by ApoH-coated nanomagnetic beads and a home-made real-time HCV-RT-PCR, we confirmed the presence of HCV for all samples from a clinical collection of HCV-seropositive patients exhibiting an RT-PCR COBAS® TaqMan® HCV Test, v2.0 (COBAS)-positive result. In contrast, for HCV-seropositive patients with either low HCV-load as determined with COBAS or exhibiting HCV-negative COBAS results, the addition of the two-step ApoH-HCV-capture and HCV-detection process was able to increase the sensitivity of HCV detection or more interestingly, detect in a genotype sequence-independent manner, a high-proportion (44%) of HCV/RNA-positive among the COBAS HCV-negative patients. Thus, the immune interaction between Apo

  1. Arsenic affects expression and processing of amyloid precursor protein (APP) in primary neuronal cells overexpressing the Swedish mutation of human APP.

    PubMed

    Zarazúa, Sergio; Bürger, Susanne; Delgado, Juan M; Jiménez-Capdeville, Maria E; Schliebs, Reinhard

    2011-06-01

    Arsenic poisoning due to contaminated water and soil, mining waste, glass manufacture, select agrochemicals, as well as sea food, affects millions of people world wide. Recently, an involvement of arsenic in Alzheimer's disease (AD) has been hypothesized (Gong and O'Bryant, 2010). The present study stresses the hypothesis whether sodium arsenite, and its main metabolite, dimethylarsinic acid (DMA), may affect expression and processing of the amyloid precursor protein (APP), using the cholinergic cell line SN56.B5.G4 and primary neuronal cells overexpressing the Swedish mutation of APP, as experimental approaches. Exposure of cholinergic SN56.B5.G4 cells with either sodium arsenite or DMA decreased cell viability in a concentration- and exposure-time dependent manner, and affected the activities of the cholinergic enzymes acetylcholinesterase and choline acetyltransferase. Both sodium arsenite and DMA exposure of SN56.B5.G4 cells resulted in enhanced level of APP, and sAPP in the membrane and cytosolic fractions, respectively. To reveal any effect of arsenic on APP processing, the amounts of APP cleavage products, sAPPβ, and β-amyloid (Aβ) peptides, released into the culture medium of primary neuronal cells derived from transgenic Tg2576 mice, were assessed by ELISA. Following exposure of neuronal cells by sodium arsenite for 12h, the membrane-bound APP level was enhanced, the amount of sAPPβ released into the culture medium was slightly higher, while the levels of Aβ peptides in the culture medium were considerably lower as compared to that assayed in the absence of any drug. The sodium arsenite-induced reduction of Aβ formation suggests an inhibition of the APP γ-cleavage step by arsenite. In contrast, DMA exposure of neuronal cells considerably increased formation of Aβ and sAPPβ, accompanied by enhanced membrane APP level. The DMA-induced changes in APP processing may be the result of the enhanced APP expression. Alternatively, increased Aβ production

  2. Dispersible amyloid β-protein oligomers, protofibrils, and fibrils represent diffusible but not soluble aggregates: their role in neurodegeneration in amyloid precursor protein (APP) transgenic mice.

    PubMed

    Rijal Upadhaya, Ajeet; Capetillo-Zarate, Estibaliz; Kosterin, Irina; Abramowski, Dorothee; Kumar, Sathish; Yamaguchi, Haruyasu; Walter, Jochen; Fändrich, Marcus; Staufenbiel, Matthias; Thal, Dietmar Rudolf

    2012-11-01

    Soluble amyloid β-protein (Aβ) aggregates have been identified in the Alzheimer's disease (AD) brain. Dispersed Aβ aggregates in the brain parenchyma are different from soluble, membrane-associated and plaque-associated solid aggregates. They are in mixture with the extra- or intracellular fluid but can be separated from soluble proteins by ultracentrifugation. To clarify the role of dispersible Aβ aggregates for neurodegeneration we analyzed 2 different amyloid precursor protein (APP)-transgenic mouse models. APP23 mice overexpress human mutant APP with the Swedish mutation. APP51/16 mice express high levels of human wild type APP. Both mice develop Aβ-plaques. Dendritic degeneration, neuron loss, and loss of asymmetric synapses were seen in APP23 but not in APP51/16 mice. The soluble and dispersible fractions not separated from one another were received as supernatant after centrifugation of native forebrain homogenates at 14,000 × g. Subsequent ultracentrifugation separated the soluble, i.e., the supernatant, from the dispersible fraction, i.e., the resuspended pellet. The major biochemical difference between APP23 and APP51/16 mice was that APP23 mice exhibited higher levels of dispersible Aβ oligomers, protofibrils and fibrils precipitated with oligomer (A11) and protofibril/fibril (B10AP) specific antibodies than APP51/16 mice. These differences, rather than soluble Aβ and Aβ plaque pathology were associated with dendritic degeneration, neuron, and synapse loss in APP23 mice in comparison with APP51/16 mice. Immunoprecipitation of dispersible Aβ oligomers, protofibrils, and fibrils revealed that they were associated with APP C-terminal fragments (APP-CTFs). These results indicate that dispersible Aβ oligomers, protofibrils, and fibrils represent an important pool of Aβ aggregates in the brain that critically interact with membrane-associated APP C-terminal fragments. The concentration of dispersible Aβ aggregates, thereby, presumably determines

  3. The roles of amyloid precursor protein (APP) in neurogenesis, implications to pathogenesis and therapy of Alzheimer disease (AD)

    PubMed Central

    Ma, Quan-hong; Xu, Xiao-hong

    2011-01-01

    The amyloid-beta (Aβ) peptide is the derivative of amyloid precursor protein (APP) generated through sequential proteolytic processing by β- and γ-secretases. Excessive accumulation of Aβ, the main constituent of amyloid plaques, has been implicated in the etiology of Alzheimer disease (AD). It was found recently that the impairments of neurogenesis in brain were associated with the pathogenesis of AD. Furthermore recent findings implicated that APP could function to influence proliferation of neural progenitor cells (NPC) and might regulate transcriptional activity of various genes. Studies demonstrated that influence of neurogenesis by APP is conferred differently via its two separate domains, soluble secreted APPs (sAPPs, mainly sAPPα) and APP intracellular domain (AICD). The sAPPα was shown to be neuroprotective and important to neurogenesis, whereas AICD was found to negatively modulate neurogenesis. Furthermore, it was demonstrated recently that microRNA could function to regulate APP expression, APP processing, Aβ accumulation and subsequently influence neurotoxicity and neurogenesis related to APP, which was implicated to AD pathogenesis, especially for sporadic AD. Based on data accumulated, secretase balances were proposed. These secretase balances could influence the downstream balance related to regulation of neurogenesis by AICD and sAPPα as well as balance related to influence of neuron viability by Aβ and sAPPα. Disruption of these secretase balances could be culprits to AD onset. PMID:21785276

  4. The roles of amyloid precursor protein (APP) in neurogenesis: Implications to pathogenesis and therapy of Alzheimer disease.

    PubMed

    Zhou, Zhi-dong; Chan, Christine Hui-shan; Ma, Quan-hong; Xu, Xiao-hong; Xiao, Zhi-cheng; Tan, Eng-king

    2011-01-01

    The amyloid-beta (Aβ) peptide is the derivative of amyloid precursor protein (APP) generated through sequential proteolytic processing by β- and γ-secretases. Excessive accumulation of Aβ, the main constituent of amyloid plaques, has been implicated in the etiology of Alzheimer's disease (AD). It was found recently that the impairments of neurogenesis in brain were associated with the pathogenesis of AD. Furthermore recent findings implicated that APP could function to influence proliferation of neural progenitor cells (NPC) and might regulate transcriptional activity of various genes. Studies demonstrated that influence of neurogenesis by APP is conferred differently via its two separate domains, soluble secreted APPs (sAPPs, mainly sAPPα) and APP intracellular domain (AICD). The sAPPα was shown to be neuroprotective and important to neurogenesis, whereas AICD was found to negatively modulate neurogenesis. Furthermore, it was demonstrated recently that microRNA could function to regulate APP expression, APP processing, Aβ accumulation and subsequently influence neurotoxicity and neurogenesis related to APP, which was implicated to AD pathogenesis, especially for sporadic AD. Based on data accumulated, secretase balances were proposed. These secretase balances could influence the downstream balance related to regulation of neurogenesis by AICD and sAPPα as well as balance related to influence of neuron viability by Aβ and sAPPα. Disruption of these secretase balances could be culprits to AD onset.

  5. Environmental temperature and stocking density effects on acute phase proteins, heat shock protein 70, circulating corticosterone and performance in broiler chickens

    NASA Astrophysics Data System (ADS)

    Najafi, Pardis; Zulkifli, Idrus; Amat Jajuli, Nurfarahin; Farjam, Abdoreza Soleimani; Ramiah, Suriya Kumari; Amir, Anna Aryani; O'Reily, Emily; Eckersall, David

    2015-11-01

    An experiment was conducted to determine the effect of different stocking densities on serum corticosterone (CORT), ovotransferrin (OVT), α1-acid glycoprotein (AGP) and ceruloplasmin (CP) concentrations, brain heat shock protein (HSP) 70 expression and performance in broiler chickens exposed to unheated and heated conditions. Day-old chicks were stocked at 0.100 m2/bird (low density (LD)) or 0.063 m2/bird (high density (HD)), in battery cages and housed in environmentally controlled rooms. From 21 to 35 days of age, birds from each stocking density group were exposed to either 24 or 32 °C. Growth performance was recorded during the heat treatment period, and blood and brain samples were collected to determine CORT, OVT, AGP, CP and HSP 70 levels on day 35. Heat treatment but not stocking density was detrimental to growth performance. There were significant temperature × density interactions for CORT, CP and OVT on day 35. Although HD elevated CORT, CP and OVT when compared to LD, the effects of the former were more obvious under heated condition. Both temperature and density had significant effect on AGP and HSP 70. In conclusion, irrespective of temperature, high stocking density was physiologically stressful to broiler chickens, as indicated by CORT, AGP, CP, OVT and HSP 70, but not detrimental to growth performance and survivability. As it was shown in the present study, AGP, CP and OVT could be useful biomarkers to determine the effect of overcrowding and high temperature on the welfare of broiler chickens.

  6. Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats.

    PubMed

    Guttman, O; Baranovski, B M; Schuster, R; Kaner, Z; Freixo-Lima, G S; Bahar, N; Kalay, N; Mizrahi, M I; Brami, I; Ochayon, D E; Lewis, E C

    2015-02-01

    One would assume that the anti-inflammatory activity of α1-anti-trypsin (AAT) is the result of inhibiting neutrophil enzymes. However, AAT exhibits tolerogenic activities that are difficult to explain by serine-protease inhibition or by reduced inflammatory parameters. Targets outside the serine-protease family have been identified, supporting the notion that elastase inhibition, the only functional factory release criteria for clinical-grade AAT, is over-emphasized. Non-obvious developments in the understanding of AAT biology disqualify it from being a straightforward anti-inflammatory agent: AAT does not block dendritic cell activities, nor does it promote viral and tumour susceptibilities, stunt B lymphocyte responses or render treated patients susceptible to infections; accordingly, outcomes of elevated AAT do not overlap those attained by immunosuppression. Aside from the acute-phase response, AAT rises during the third trimester of pregnancy and also in advanced age. At the molecular level, AAT docks onto cholesterol-rich lipid-rafts and circulating lipid particles, directly binds interleukin (IL)-8, ADAM metallopeptidase domain 17 (ADAM17) and danger-associated molecular pattern (DAMP) molecules, and its activity is lost to smoke, high glucose levels and bacterial proteases, introducing a novel entity - 'relative AAT deficiency'. Unlike immunosuppression, AAT appears to help the immune system to distinguish between desired responses against authentic threats, and unwanted responses fuelled by a positive feedback loop perpetuated by, and at the expense of, inflamed injured innocent bystander cells. With a remarkable clinical safety record, AAT treatment is currently tested in clinical trials for its potential benefit in a variety of categorically distinct pathologies that share at least one common driving force: cell injury.

  7. The analysis of the acute phase response during the course of Trypanosoma carassii infection in the goldfish (Carassius auratus L.).

    PubMed

    Kovacevic, Nikolina; Hagen, Mariel O; Xie, Jiasong; Belosevic, Miodrag

    2015-11-01

    The expression of genes encoding the acute phase proteins (APP) during the course of Trypanasoma carassii infection in the goldfish was determined using quantitative PCR. Significant changes in the mRNA levels of ceruloplasmin (Cp), C-reactive protein (CRP), transferrin (Tf), hemopexin (Hx) and serum amyloid A (SAA) were observed in the kidney, liver and spleen at various days post infection (dpi). Of the five acute phase protein genes examined, CRP and SAA exhibited the highest expression in the tissues during the acute infection. Cp and Tf were up-regulated throughout the acute course of infection in the liver. During the chronic phase of the infection, APP expression in the liver was similar to that in the non-infected control fish. At 7 dpi, Cp, Tf and Hx were down-regulated in the spleen, and Cp and Tf kidney, but their mRNA levels gradually returned to those of control non-infected fish. In contrast, during the chronic phase of the infection, there was an up-regulation of Cp, Hx and Tf in the spleen, and Tf and SAA in the kidney. The goldfish CRP was cloned and functionally characterized. CRP was differentially expressed in normal goldfish immune cells, with highest expression in monocytes and lowest expression in mature macrophages. A recombinant goldfish CRP (rgfCRP) was generated using prokaryotic expression. rgfCRP enhanced complement-mediated killing of trypanosomes in vitro, and the lysis increased after addition of immune serum. rgfCRP did not affect the production of reactive oxygen and nitrogen intermediates by monocytes and macrophages, respectively.

  8. [Rehabilitation for myositis in acute phase].

    PubMed

    Abe, Kazuo

    2007-04-01

    Polymyositis and dermatomyositis (PM/DM) are representative inflammatory muscle diseases. In treatment of PM/DM, drug therapies are cardinal but rehabilitation may be another option. Since muscles with PM/DM are fragile for muscle exercise, rehabilitation has been recommended mainly in chronic phase. Some researchers considered that rehabilitation for PM/DM patients in acute phase may improve their functional prognosis without major sideeffect. However, there are controversies about rehabilitation for PM/DM patients from acute phase. To consider advisability, I reviewed literatures concerning rehabilitation for PM/DM patients in acute phase.

  9. Alzheimer's disease against peptides products of enzymatic cleavage of APP protein. Forming and variety of fibrillating peptides - some aspects.

    PubMed

    Marszałek, Małgorzata

    2016-01-01

    Various and different peptides products resulting from enzymatic protein cleavage of Amyloid Precursor Proteins (APP) are the main agents in the pathophysiology of Alzheimer's disease (AD). Although relatively well-known, they still arouse interest leading to further intense and wide-ranging research. Their biology and physico-chemical properties still are challenging for basic, experimental research and are matter of scientific debate. The APP itself and its functions are still somewhat enigmatic and therefore it is also called the All Purpose Protein. Apart from well known amyloidogenic and antiamyloidogenic (non-amyloidogenic) enzymatic cleavage pathways of APP protein this paper deals with issues connected with other, alternative pathways that seem to be interesting and important as well. They lead to other than Aβ forms of peptide products such as: N-APP, N-terminally cleavage products of APP (N-terminally truncated ) Aβ', γ- secretase-independent pathway products that involve concerted cleavages of APP by α- and β-secretase or products that emerge after caspase activity. Presence of all these peptides in CSF, ISF, blood serum and urine of the AD patients is crucial for successful diagnosis, giving rise to hope of their better detection and potentially better treatment of AD. Therefore, newly discovered products of the AβT domain cleavage (Aβ total i.e. full fibrillating domain of APP), Aβ type products and other peptides because of their biology and physico-chemical properties are very intriguing and deserve further experimental research. On the other hand after better recognition and better understanding their biology they might be enormously useful in the future for diagnosis and therapy for example Alzheimer's disease. PMID:27383575

  10. Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury.

    PubMed

    Hayashi, Takahito; Ago, Kazutoshi; Nakamae, Takuma; Higo, Eri; Ogata, Mamoru

    2015-09-01

    Immunostaining for beta-amyloid precursor protein (APP) is recognized as an effective tool for detecting traumatic axonal injury, but it also detects axonal injury due to ischemic or other metabolic causes. Previously, we reported two different patterns of APP staining: labeled axons oriented along with white matter bundles (pattern 1) and labeled axons scattered irregularly (pattern 2) (Hayashi et al. (Leg Med (Tokyo) 11:S171-173, 2009). In this study, we investigated whether these two patterns are consistent with patterns of trauma and hypoxic brain damage, respectively. Sections of the corpus callosum from 44 cases of blunt head injury and equivalent control tissue were immunostained for APP. APP was detected in injured axons such as axonal bulbs and varicose axons in 24 of the 44 cases of head injuries that also survived for three or more hours after injury. In 21 of the 24 APP-positive cases, pattern 1 alone was observed in 14 cases, pattern 2 alone was not observed in any cases, and both patterns 1 and 2 were detected in 7 cases. APP-labeled injured axons were detected in 3 of the 44 control cases, all of which were pattern 2. These results suggest that pattern 1 indicates traumatic axonal injury, while pattern 2 results from hypoxic insult. These patterns may be useful to differentiate between traumatic and nontraumatic axonal injuries. PMID:26249371

  11. Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury.

    PubMed

    Hayashi, Takahito; Ago, Kazutoshi; Nakamae, Takuma; Higo, Eri; Ogata, Mamoru

    2015-09-01

    Immunostaining for beta-amyloid precursor protein (APP) is recognized as an effective tool for detecting traumatic axonal injury, but it also detects axonal injury due to ischemic or other metabolic causes. Previously, we reported two different patterns of APP staining: labeled axons oriented along with white matter bundles (pattern 1) and labeled axons scattered irregularly (pattern 2) (Hayashi et al. (Leg Med (Tokyo) 11:S171-173, 2009). In this study, we investigated whether these two patterns are consistent with patterns of trauma and hypoxic brain damage, respectively. Sections of the corpus callosum from 44 cases of blunt head injury and equivalent control tissue were immunostained for APP. APP was detected in injured axons such as axonal bulbs and varicose axons in 24 of the 44 cases of head injuries that also survived for three or more hours after injury. In 21 of the 24 APP-positive cases, pattern 1 alone was observed in 14 cases, pattern 2 alone was not observed in any cases, and both patterns 1 and 2 were detected in 7 cases. APP-labeled injured axons were detected in 3 of the 44 control cases, all of which were pattern 2. These results suggest that pattern 1 indicates traumatic axonal injury, while pattern 2 results from hypoxic insult. These patterns may be useful to differentiate between traumatic and nontraumatic axonal injuries.

  12. Combinations of Polymorphic Markers of Chemokine Genes, Their Receptors and Acute Phase Protein Genes As Potential Predictors of Coronary Heart Diseases

    PubMed Central

    Nasibullin, T.R.; Yagafarova, L.F.; Yagafarov, I.R.; Timasheva, Y.R.; Erdman, V.V.; Tuktarova, I.A.; Mustafina, O.E.

    2016-01-01

    Atherosclerosis, the main factor in the development of coronary heart diseases (CHD), is an inflammatory response to endothelial layer damage in the arterial bed. We have analyzed the association between CHD and the polymorphic markers of genes that control the synthesis of proteins involved in the processes of adhesion and chemotaxis of immunocompetent cells: rs1024611 (–2518A>G, CCL2 gene), rs1799864 (V64I, CCR2 gene), rs3732378 (T280M, CX3CR1 gene), rs1136743 (A70V, SAA1 gene), and rs1205 (2042C>T, CRP gene) in 217 patients with CHD and 250 controls. Using the Monte Carlo method and Markov chains (APSampler), we revealed a combination of alleles/genotypes associated with both a reduced and increased risk of CHD. The most significant alleles/genotypes areSAA1*T/T+CRP*C+CX3CR1*G/A (Pperm = 0.0056, OR = 0.07 95%CI 0.009–0.55),SAA1*T+CRP*T+CCR2*G/A+CX3CR1*G (Pperm = 0.0063, OR = 14.58 95%CI 1.88–113.04), SAA1*T+CCR2*A+CCL2* G/G (Pperm = 0.0351, OR = 10.77 95%CI 1.35–85.74). PMID:27099791

  13. The APP-Interacting Protein FE65 is Required for Hippocampus-Dependent Learning and Long-Term Potentiation

    ERIC Educational Resources Information Center

    Wang, Yan; Zhang, Ming; Moon, Changjong; Hu, Qubai; Wang, Baiping; Martin, George; Sun, Zhongsheng; Wang, Hongbing

    2009-01-01

    FE65 is expressed predominantly in the brain and interacts with the C-terminal domain of [beta]-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with isoform-specific FE65 knockout (p97FE65[superscript -/-]) mice. When examined using the Morris water maze,…

  14. Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase.

    PubMed

    Kobayashi, Masatake; Nanri, Kazunori; Taguchi, Takeshi; Ishiko, Tomoko; Yoshida, Masaharu; Yoshikawa, Noriko; Sugisaki, Kentaro; Tanaka, Nobuyuki

    2015-02-01

    Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.

  15. Holo-APP and G-protein-mediated signaling are required for sAPPα-induced activation of the Akt survival pathway

    PubMed Central

    Milosch, N; Tanriöver, G; Kundu, A; Rami, A; François, J-C; Baumkötter, F; Weyer, S W; Samanta, A; Jäschke, A; Brod, F; Buchholz, C J; Kins, S; Behl, C; Müller, U C; Kögel, D

    2014-01-01

    Accumulating evidence indicates that loss of physiologic amyloid precursor protein (APP) function leads to reduced neuronal plasticity, diminished synaptic signaling and enhanced susceptibility of neurons to cellular stress during brain aging. Here we investigated the neuroprotective function of the soluble APP ectodomain sAPPα (soluble APPα), which is generated by cleavage of APP by α-secretase along the non-amyloidogenic pathway. Recombinant sAPPα protected primary hippocampal neurons and SH-SY5Y neuroblastoma cells from cell death induced by trophic factor deprivation. We show that this protective effect is abrogated in neurons from APP-knockout animals and APP-depleted SH-SY5Y cells, but not in APP-like protein 1- and 2- (APLP1 and APLP2) depleted cells, indicating that expression of membrane-bound holo-APP is required for sAPPα-dependent neuroprotection. Trophic factor deprivation diminished the activity of the Akt survival pathway. Strikingly, both recombinant sAPPα and the APP-E1 domain were able to stimulate Akt activity in wild-type (wt) fibroblasts, SH-SY5Y cells and neurons, but failed to rescue in APP-deficient neurons or fibroblasts. The ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) inhibitor GI254023X exacerbated neuron death in organotypic (hippocampal) slice cultures of wt mice subjected to trophic factor and glucose deprivation. This cell death-enhancing effect of GI254023X could be completely rescued by applying exogenous sAPPα. Interestingly, sAPPα-dependent Akt induction was unaffected in neurons of APP-ΔCT15 mice that lack the C-terminal YENPTY motif of the APP intracellular region. In contrast, sAPPα-dependent rescue of Akt activation was completely abolished in APP mutant cells lacking the G-protein interaction motif located in the APP C-terminus and by blocking G-protein-dependent signaling with pertussis toxin. Collectively, our data provide new mechanistic insights into the physiologic role of APP in

  16. Holo-APP and G-protein-mediated signaling are required for sAPPα-induced activation of the Akt survival pathway.

    PubMed

    Milosch, N; Tanriöver, G; Kundu, A; Rami, A; François, J-C; Baumkötter, F; Weyer, S W; Samanta, A; Jäschke, A; Brod, F; Buchholz, C J; Kins, S; Behl, C; Müller, U C; Kögel, D

    2014-01-01

    Accumulating evidence indicates that loss of physiologic amyloid precursor protein (APP) function leads to reduced neuronal plasticity, diminished synaptic signaling and enhanced susceptibility of neurons to cellular stress during brain aging. Here we investigated the neuroprotective function of the soluble APP ectodomain sAPPα (soluble APPα), which is generated by cleavage of APP by α-secretase along the non-amyloidogenic pathway. Recombinant sAPPα protected primary hippocampal neurons and SH-SY5Y neuroblastoma cells from cell death induced by trophic factor deprivation. We show that this protective effect is abrogated in neurons from APP-knockout animals and APP-depleted SH-SY5Y cells, but not in APP-like protein 1- and 2- (APLP1 and APLP2) depleted cells, indicating that expression of membrane-bound holo-APP is required for sAPPα-dependent neuroprotection. Trophic factor deprivation diminished the activity of the Akt survival pathway. Strikingly, both recombinant sAPPα and the APP-E1 domain were able to stimulate Akt activity in wild-type (wt) fibroblasts, SH-SY5Y cells and neurons, but failed to rescue in APP-deficient neurons or fibroblasts. The ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) inhibitor GI254023X exacerbated neuron death in organotypic (hippocampal) slice cultures of wt mice subjected to trophic factor and glucose deprivation. This cell death-enhancing effect of GI254023X could be completely rescued by applying exogenous sAPPα. Interestingly, sAPPα-dependent Akt induction was unaffected in neurons of APP-ΔCT15 mice that lack the C-terminal YENPTY motif of the APP intracellular region. In contrast, sAPPα-dependent rescue of Akt activation was completely abolished in APP mutant cells lacking the G-protein interaction motif located in the APP C-terminus and by blocking G-protein-dependent signaling with pertussis toxin. Collectively, our data provide new mechanistic insights into the physiologic role of APP in

  17. Age and gene overexpression interact to abolish nesting behavior in Tg2576 amyloid precursor protein (APP) mice.

    PubMed

    Wesson, Daniel W; Wilson, Donald A

    2011-01-01

    Elucidating the modulators of social behavioral is important in understanding the neural basis of behavior and in developing methods to enhance behavior in cases of disorder. The work here stems from the observation that the Alzheimer's disease mouse model Tg2576, overexpressing human mutations of the amyloid-β precursor protein (APP), fails to construct nests when supplied paper towels in their home cages. Experiments using commercially available cotton nesting material found similar results. Additional experiments revealed that the genotype effect is progressively modulated by age in APP mice but not their WT counterparts. There was no effect of sex on nesting behavior in any group. Finally, this effect was independent of ambient temperature - even when subjected to a cold environment, APP mice fail to build nests whereas WT mice do. These results suggest that the APP gene plays a role in affiliative behaviors and are discussed in relation to disorders characteristic of mutations in the APP gene and in affective dysfunction, including Alzheimer's disease. PMID:20804789

  18. Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins.

    PubMed

    Miller, L L

    1976-01-01

    The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs-Ringer bicarbonate buffer containing 3 per cent bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, alpah1-acid glycoprotein, alpha2-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 mug.) used was insufficient to induce synthesis of alpha2-acute phase globulin, net syntheses of albumin, fibrogen, alpha1-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and alpha1-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.

  19. Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice

    PubMed Central

    Bedrosian, Tracy A.; Herring, Kamillya L.; Weil, Zachary M.; Nelson, Randy J.

    2011-01-01

    Both normal aging and dementia are associated with dysregulation of the biological clock, which contributes to disrupted circadian organization of physiology and behavior. Diminished circadian organization in conjunction with the loss of cholinergic input to the cortex likely contributes to impaired cognition and behavior. One especially notable and relatively common circadian disturbance among the aged is “sundowning syndrome,” which is characterized by exacerbated anxiety, agitation, locomotor activity, and delirium during the hours before bedtime. Sundowning has been reported in both dementia patients and cognitively intact elderly individuals living in institutions; however, little is known about temporal patterns in anxiety and agitation, and the neurobiological basis of these rhythms remains unspecified. In the present study, we explored the diurnal pattern of anxiety-like behavior in aged and amyloid precursor protein (APP) transgenic mice. We then attempted to treat the observed behavioral disturbances in the aged mice using chronic nightly melatonin treatment. Finally, we tested the hypothesis that time-of-day differences in acetylcholinesterase and choline acetyltransferase expression and general neuronal activation (i.e., c-Fos expression) coincide with the behavioral symptoms. Our results show a temporal pattern of anxiety-like behavior that emerges in elderly mice. This behavioral pattern coincides with elevated locomotor activity relative to adult mice near the end of the dark phase, and with time-dependent changes in basal forebrain acetylcholinesterase expression. Transgenic APP mice show a similar behavioral phenomenon that is not observed among age-matched wild-type mice. These results may have useful applications to the study and treatment of age- and dementia-related circadian behavioral disturbances, namely, sundowning syndrome. PMID:21709248

  20. Fuzzy logic for personalized healthcare and diagnostics: FuzzyApp--a fuzzy logic based allergen-protein predictor.

    PubMed

    Saravanan, Vijayakumar; Lakshmi, P T V

    2014-09-01

    The path to personalized medicine demands the use of new and customized biopharmaceutical products containing modified proteins. Hence, assessment of these products for allergenicity becomes mandatory before they are introduced as therapeutics. Despite the availability of different tools to predict the allergenicity of proteins, it remains challenging to predict the allergens and nonallergens, when they share significant sequence similarity with known nonallergens and allergens, respectively. Hence, we propose "FuzzyApp," a novel fuzzy rule based system to evaluate the quality of the query protein to be an allergen. It measures the allergenicity of the protein based on the fuzzy IF-THEN rules derived from five different modules. On various datasets, FuzzyApp outperformed other existing methods and retained balance between sensitivity and specificity, with positive Mathew's correlation coefficient. The high specificity of allergen-like putative nonallergens (APN) revealed the FuzzyApp's capability in distinguishing the APN from allergens. In addition, the error analysis and whole proteome dataset analysis suggest the efficiency and consistency of the proposed method. Further, FuzzyApp predicted the Tropomyosin from various allergenic and nonallergenic sources accurately. The web service created allows batch sequence submission, and outputs the result as readable sentences rather than values alone, which assists the user in understanding why and what features are responsible for the prediction. FuzzyApp is implemented using PERL CGI and is freely accessible at http://fuzzyapp.bicpu.edu.in/predict.php . We suggest the use of Fuzzy logic has much potential in biomarker and personalized medicine research to enhance predictive capabilities of post-genomics diagnostics.

  1. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  2. A macromolecular complex involving the amyloid precursor protein (APP) and the cytosolic adapter FE65 is a negative regulator of axon branching

    PubMed Central

    Ikin, Annat F.; Sabo, Shasta L.; Lanier, Lorene M.; Buxbaum, Joseph D.

    2011-01-01

    Several studies suggest a role for the amyloid precursor protein (APP) in neurite outgrowth and synaptogenesis, but the downstream interactions that mediate the function of APP during neuron development are unknown. By introducing interaction-deficient FE65 into cultured hippocampal neurons using adenovirus, we show that a complex including APP, FE65 and an additional protein is involved in neurite outgrowth at early stages of neuronal development. Both FE65 that is unable to interact with APP (PID2 mutants) or a WW mutant increased axon branching. Although the FE65 mutants did not affect total neurite output, both mutants decreased axon segment length, consistent with an overall slowing of axonal growth cones. FE65 mutants did not alter the localization of either APP or FE65 in axonal growth cones, suggesting that the effects on neurite outgrowth are achieved by alterations in local complex formation within the axonal growth cone. PMID:17383198

  3. Genomic mosaicism with increased amyloid precursor protein (APP) gene copy number in single neurons from sporadic Alzheimer's disease brains

    PubMed Central

    Bushman, Diane M; Kaeser, Gwendolyn E; Siddoway, Benjamin; Westra, Jurgen W; Rivera, Richard R; Rehen, Stevens K; Yung, Yun C; Chun, Jerold

    2015-01-01

    Previous reports have shown that individual neurons of the brain can display somatic genomic mosaicism of unknown function. In this study, we report altered genomic mosaicism in single, sporadic Alzheimer's disease (AD) neurons characterized by increases in DNA content and amyloid precursor protein (APP) gene copy number. AD cortical nuclei displayed large variability with average DNA content increases of ∼8% over non-diseased controls that were unrelated to trisomy 21. Two independent single-cell copy number analyses identified amplifications at the APP locus. The use of single-cell qPCR identified up to 12 copies of APP in sampled neurons. Peptide nucleic acid (PNA) probes targeting APP, combined with super-resolution microscopy detected primarily single fluorescent signals of variable intensity that paralleled single-cell qPCR analyses. These data identify somatic genomic changes in single neurons, affecting known and unknown loci, which are increased in sporadic AD, and further indicate functionality for genomic mosaicism in the CNS. DOI: http://dx.doi.org/10.7554/eLife.05116.001 PMID:25650802

  4. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    PubMed Central

    Saber, Anne T; Jacobsen, Nicklas R; Jackson, Petra; Poulsen, Sarah Søs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Håkan; Vogel, Ulla

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. How to cite this article: WIREs Nanomed Nanobiotechnol 2014, 6:517–531. doi: 10.1002/wnan.1279 PMID:24920450

  5. Mitochondrial dysfunction in a transgenic mouse model expressing human amyloid precursor protein (APP) with the Arctic mutation.

    PubMed

    Rönnbäck, Annica; Pavlov, Pavel F; Mansory, Mansorah; Gonze, Prisca; Marlière, Nicolas; Winblad, Bengt; Graff, Caroline; Behbahani, Homira

    2016-02-01

    Accumulation of amyloid β-peptide (Aβ) in the brain is an important event in the pathogenesis of Alzheimer disease. We have used a transgenic mouse model expressing human amyloid precursor protein (APP) with the Arctic mutation to investigate whether Aβ deposition is correlated with mitochondrial functions in these animals. We found evidence of mitochondrial dysfunction (i.e., decreased mitochondrial membrane potential, increased production of reactive oxygen species and oxidative DNA damage) at 6 months of age, when the mice showed very mild Aβ deposition. More pronounced mitochondrial abnormalities were present in 24-month-old TgAPParc mice with more extensive Aβ pathology. This study demonstrates for the first time mitochondrial dysfunction in transgenic mice with a mutation within the Aβ peptide (the Arctic APP mutation), and confirms previous studies suggesting that mitochondrial dysfunction and oxidative stress is an early event in the pathogenesis of Alzheimer disease. This study demonstrates mitochondrial dysfunction in transgenic mice with a mutation within the amyloid beta (Aβ) peptide (the Arctic amyloid precursor protein (APP) mutation). We found evidence of mitochondrial dysfunction (i.e. decreased mitochondrial membrane potential (MMP), increased production of reactive oxygen species (ROS) and oxidative DNA damage) at 6 months of age, when very mild Aβ deposition is present in the mice. Also, the cytochrome c (COX) activity was significantly decreased in mitochondria from transgenic mice at 24 months of age.

  6. Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype

    PubMed Central

    Baybutt, Herbert; Diack, Abigail B.; Kellett, Katherine A. B.; Piccardo, Pedro; Manson, Jean C.

    2016-01-01

    The cellular prion protein (PrPC) has been proposed to play an important role in the pathogenesis of Alzheimer’s disease. In cellular models PrPC inhibited the action of the β-secretase BACE1 on wild type amyloid precursor protein resulting in a reduction in amyloid-β (Aβ) peptides. Here we have assessed the effect of genetic ablation of PrPC in transgenic mice expressing human wild type amyloid precursor protein (line I5). Deletion of PrPC had no effect on the α- and β-secretase proteolysis of the amyloid precursor protein (APP) nor on the amount of Aβ38, Aβ40 or Aβ42 in the brains of the mice. In addition, ablation of PrPC did not alter Aβ deposition or histopathology phenotype in this transgenic model. Thus using this transgenic model we could not provide evidence to support the hypothesis that PrPC regulates Aβ production. PMID:27447728

  7. Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype.

    PubMed

    Whitehouse, Isobel J; Brown, Deborah; Baybutt, Herbert; Diack, Abigail B; Kellett, Katherine A B; Piccardo, Pedro; Manson, Jean C; Hooper, Nigel M

    2016-01-01

    The cellular prion protein (PrPC) has been proposed to play an important role in the pathogenesis of Alzheimer's disease. In cellular models PrPC inhibited the action of the β-secretase BACE1 on wild type amyloid precursor protein resulting in a reduction in amyloid-β (Aβ) peptides. Here we have assessed the effect of genetic ablation of PrPC in transgenic mice expressing human wild type amyloid precursor protein (line I5). Deletion of PrPC had no effect on the α- and β-secretase proteolysis of the amyloid precursor protein (APP) nor on the amount of Aβ38, Aβ40 or Aβ42 in the brains of the mice. In addition, ablation of PrPC did not alter Aβ deposition or histopathology phenotype in this transgenic model. Thus using this transgenic model we could not provide evidence to support the hypothesis that PrPC regulates Aβ production. PMID:27447728

  8. c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration

    PubMed Central

    Ahn, Ji-Hwan; So, Sang-Pil; Kim, Na-Young; Kim, Hyun-Ju; Yoon, Seung-Yong; Kim, Dong-Hou

    2016-01-01

    Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer’s disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce neuronal death. We previously showed that OA increased levels of APP and induced accumulation of APP in axonal swellings. In this study, we found that in OA-treated neurons, phosphorylation of APP at Thr668 increased and accumulated in axonal swellings by c-jun N-terminal kinase (JNK), and not by Cdk5 or ERK/MAPK. These results suggest that JNK may be one of therapeutic targets for the treatment of AD. [BMB Reports 2016; 49(7): 376-381] PMID:26839154

  9. Immune and acute phase response in pigs experimentally infected with H1N2 swine influenza virus.

    PubMed

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Kwit, Krzysztof

    2012-12-01

    Acute phase proteins (APPs) and immune responses in pigs after experimental infection with H1N2 swine influenza virus (SwH1N2) were studied. Eight piglets were infected intranasally with SwH1N2. Four served as controls. Antibodies against swine influenza virus (SIV)s were measured by hemagglutination inhibition assay. The proliferation assay was used to measure influenza-specific cell-mediated response. Hematological parameters were measured on a hematology analyzer. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA) and pig major APP (Pig-MAP) concentrations in serum were measured using commercial ELISAs. Antibodies against SwH1N2 in the serum of infected pigs were detected from 7 dpi. SwH1N2-specific T-cell response was observed from 5 dpi. A significant drop in lymphocyte numbers and an increase in medium-sized cell (MID) counts with no accompanying leukopenia was observed in all infected pigs from 3 to 7 dpi. In infected pigs, concentrations of CRP, Hp and SAA increased significantly when the greatest amounts of virus were shed (from 1 to 3 dpi). The level of Pig-MAP remained unchanged during study. The significant positive correlation found between maximum concentrations of SAA in serum and lung scores, makes SAA a potentially useful indicator in experimental infection studies (e.g. vaccine efficiency investigations) or as a marker for disease severity, but to confirm this hypothesis more studies are needed.

  10. Alterations of acute phase reaction and cytokine production in patients following severe burn injury.

    PubMed

    Dehne, Marius G; Sablotzki, Armin; Hoffmann, Andreas; Mühling, Jörg; Dietrich, Friedrich E; Hempelmann, Gunter

    2002-09-01

    To determine the acute immunologic reaction, mediated by cytokines, interleukines (ILs) and growth factors and the susceptibility to infections and sepsis after severe burn injury a prospective, single unit, longitudinal study of acute phase reactants and mediators who performed. After approval by the ethics committee of our hospital, we investigated the plasma concentrations of IL-2, -6, -8, -10, and -13, the soluble IL-2 receptor (sIL-2R), and the acute phase proteins procalcitonin (PCT) and C-reactive protein (CRP) at admission and every 3 days in 24 patients over a time course of 28 days after thermal injury and categorized by percent burn: < or =30% (group 1; n=12) and >30% (group 2; n=12). Shortly after burn injury we found higher concentrations of IL-2, -6, -10 and PCT in those patients >30% TBSA. During the study period, we found significant higher levels of acute phase proteins, IL-6 and -8 in patients >30% TBSA. The incidence of SIRS and MODS was three times increased in patients >30% TBSA. Our results show different patterns of cytokines and acute phase proteins in patients with different burned surface areas over a long time and continuous monitoring of a more distinct inflammatory response in these patients.

  11. Management of pemphigus vulgaris during acute phase.

    PubMed

    Kar, P K; Murthy, P S; Rajagopal, R

    2003-01-01

    We present our experience with 21 patients of pemphigus vulgaris seen over a period of 10 years managed in service hospitals during acute phase of the disease. Age groups of patients ranged from 25-45 years. Eighteen (85.7%) were young adults, 30-40 years of age. Fifteen (71.4%) were men and 6 (28.6%) were women. All the cases were hospitalized in ICU, till the acute phase of the disease subsided. Complete hematological profile, urinalysis, serum biochemistry and repeated bacterial cultures from the skin were carried out in all patients at the time of admission and thereafter weekly. The treatment comprised of potassium permanganate lotion bath (1:10,000) and 1 framycetin gauze dressing of the denuded areas, maintenance of fluid and electrolyte balance. All suspected infections and septicemia were treated with appropriate antibiotics. The corticosteroids were usually administered as a single dose of prednisolone 1 mg/kg/day. Cyclophosphamide was given at an initial dose of 50 mg/day and the dose was escalated to 100 mg/day. Once the bulk of the lesions were healed, the dose of corticosteroids was gradually lowered by approximately 50% every two weeks and cyclophosphamide was continued till patients were symptom-free. Out of 21 patients receiving corticosteroids, cyclophosphamide and other supportive therapy, 20 (95%) had undergone clinical resolution of the disease. During follow up study 15 (71.4%) patients remained symptom-free and undergone clinical remission. Five patients (23.8%) had relapse, out of which 4 (19%) remained symptom free, after subsequent treatment. There was one death (4.7%) in our study.

  12. Procalcitonin beyond the acute phase: novel biomediator properties?

    PubMed

    Panico, Carolina; Nylen, Eric

    2013-01-01

    Since inflammation has been linked to carcinogenic events, discovery of relevant biomarkers may have important preventative implications. Procalcitonin (ProCT) has been shown to be an important prognostic biomarker in severe inflammatory conditions, but there is no data regarding its biomarker role, if any, beyond the acute phase. In a recent study published in BMC Medicine, Cotoi et al. analyzed whether serum ProCT levels in healthy individuals are associated with mortality outcomes. The results are affirmative in that baseline ProCT was shown to be strongly and independently associated with all-cause and cancer mortality and with the incidence of colon cancer in men. By contrast, the study indicated that high sensitivity C-reactive protein was independently associated with cardiovascular mortality but not with cancer mortality in men. Thus, baseline levels of ProCT appear to have prognostic biomarker implications potentially related to its emerging biomediator action(s). PMID:23984981

  13. Beta-Amyloid Precursor ProteinAPP) Processing in Alzheimer's Disease (AD) and Age-Related Macular Degeneration (AMD).

    PubMed

    Zhao, Yuhai; Bhattacharjee, Surjyadipta; Jones, Brandon M; Hill, James M; Clement, Christian; Sambamurti, Kumar; Dua, Prerna; Lukiw, Walter J

    2015-08-01

    Amyloid is a generic term for insoluble, often intensely hydrophobic, fibrous protein aggregates that arise from inappropriately folded versions of naturally-occurring polypeptides. The abnormal generation and accumulation of amyloid, often referred to as amyloidogenesis, has been associated with the immune and pro-inflammatory pathology of several progressive age-related diseases of the human central nervous system (CNS) including Alzheimer's disease (AD) and age-related macular degeneration (AMD). This 'research perspective' paper reviews some of the research history, biophysics, molecular-genetics and environmental factors concerning the contribution of amyloid beta (Aβ) peptides, derived from beta-amyloid precursor proteinAPP), to AD and AMD that suggests an extensive similarity in immune and inflammatory degenerative mechanisms between these two CNS diseases.

  14. Prolyl isomerase Pin1 promotes amyloid precursor protein (APP) turnover by inhibiting glycogen synthase kinase-3β (GSK3β) activity: novel mechanism for Pin1 to protect against Alzheimer disease.

    PubMed

    Ma, Suk Ling; Pastorino, Lucia; Zhou, Xiao Zhen; Lu, Kun Ping

    2012-03-01

    Alzheimer disease (AD) is characterized by the presence of senile plaques of amyloid-β (Aβ) peptides derived from amyloid precursor protein (APP) and neurofibrillary tangles made of hyperphosphorylated Tau. Increasing APP gene dosage or expression has been shown to cause familial early-onset AD. However, whether and how protein stability of APP is regulated is unclear. The prolyl isomerase Pin1 and glycogen synthase kinase-3β (GSK3β) have been shown to have the opposite effects on APP processing and Tau hyperphosphorylation, relevant to the pathogenesis of AD. However, nothing is known about their relationship. In this study, we found that Pin1 binds to the pT330-P motif in GSK3β to inhibit its kinase activity. Furthermore, Pin1 promotes protein turnover of APP by inhibiting GSK3β activity. A point mutation either at Thr-330, the Pin1-binding site in GSK3β, or at Thr-668, the GSK3β phosphorylation site in APP, abolished the regulation of GSK3β activity, Thr-668 phosphorylation, and APP stability by Pin1, resulting in reduced non-amyloidogenic APP processing and increased APP levels. These results uncover a novel role of Pin1 in inhibiting GSK3β kinase activity to reduce APP protein levels, providing a previously unrecognized mechanism by which Pin1 protects against Alzheimer disease.

  15. Tau Protein Mediates APP Intracellular Domain (AICD)-Induced Alzheimer’s-Like Pathological Features in Mice

    PubMed Central

    Dawson, Hana N.; Pimplikar, Sanjay W.

    2016-01-01

    Amyloid precursor protein (APP) is cleaved by gamma-secretase to simultaneously generate amyloid beta (Aβ) and APP Intracellular Domain (AICD) peptides. Aβ plays a pivotal role in Alzheimer’s disease (AD) pathogenesis but recent studies suggest that amyloid-independent mechanisms also contribute to the disease. We previously showed that AICD transgenic mice (AICD-Tg) exhibit AD-like features such as tau pathology, aberrant neuronal activity, memory deficits and neurodegeneration in an age-dependent manner. Since AD is a tauopathy and tau has been shown to mediate Aβ–induced toxicity, we examined the role of tau in AICD-induced pathological features. We report that ablating endogenous tau protects AICD-Tg mice from deficits in adult neurogenesis, seizure severity, short-term memory deficits and neurodegeneration. Deletion of tau restored abnormal phosphorylation of NMDA receptors, which is likely to underlie hyperexcitability and associated excitotoxicity in AICD-Tg mice. Conversely, overexpression of wild-type human tau aggravated receptor phosphorylation, impaired adult neurogenesis, memory deficits and neurodegeneration. Our findings show that tau is essential for mediating the deleterious effects of AICD. Since tau also mediates Aβ-induced toxic effects, our findings suggest that tau is a common downstream factor in both amyloid-dependent and–independent pathogenic mechanisms and therefore could be a more effective drug target for therapeutic intervention in AD. PMID:27459671

  16. The acute phase response in parasite infection. Nippostrongylus brasiliensis in the mouse.

    PubMed Central

    Lamontagne, L R; Gauldie, J; Befus, A D; McAdam, K P; Baltz, M L; Pepys, M B

    1984-01-01

    Systemic inflammatory reactions are a prominent feature of many parasitic infections and the cellular and humoral components of the acute phase reaction may have an impact on the host-parasite relationship. We examined serum changes of four acute phase reactants: alpha 1-proteinase inhibition (alpha 1Pi); complement C3; serum amyloid A protein (SAA); and serum amyloid P component (SAP), in mice undergoing a primary infection with Nippostrongylus brasiliensis. SAA and SAP showed changes within the first 2 days of infection indicating the presence of an acute phase response associated with inflammation in the lung. Alpha 1Pi and C3 serum levels were not altered. However, all four acute phase reactants were synthesized in greater amounts by primary cultures of hepatocytes taken from infected animals at this time. Subsequently, as parasite-mediated inflammatory changes occur in the gut, both serum and hepatocyte cultures demonstrate an acute inflammatory response in all four reactants. It is proposed that the early reaction between parasites and macrophage/monocyte lead to the release of a mediator of inflammation which initiates the hepatocyte response. In this infection, at least one of the APR is shown to localize to the site of inflammation influencing the host-parasite relationship. Images Figure 2 Figure 3 PMID:6204934

  17. Acute phase response in two consecutive experimentally induced E. coli intramammary infections in dairy cows

    PubMed Central

    Suojala, Leena; Orro, Toomas; Järvinen, Hanna; Saatsi, Johanna; Pyörälä, Satu

    2008-01-01

    Background Acute phase proteins haptoglobin (Hp), serum amyloid A (SAA) and lipopolysaccharide binding protein (LBP) have suggested to be suitable inflammatory markers for bovine mastitis. The aim of the study was to investigate acute phase markers along with clinical parameters in two consecutive intramammary challenges with Escherichia coli and to evaluate the possible carry-over effect when same animals are used in an experimental model. Methods Mastitis was induced with a dose of 1500 cfu of E. coli in one quarter of six cows and inoculation repeated in another quarter after an interval of 14 days. Concentrations of acute phase proteins haptoglobin (Hp), serum amyloid A (SAA) and lipopolysaccharide binding protein (LBP) were determined in serum and milk. Results In both challenges all cows became infected and developed clinical mastitis within 12 hours of inoculation. Clinical disease and acute phase response was generally milder in the second challenge. Concentrations of SAA in milk started to increase 12 hours after inoculation and peaked at 60 hours after the first challenge and at 44 hours after the second challenge. Concentrations of SAA in serum increased more slowly and peaked at the same times as in milk; concentrations in serum were about one third of those in milk. Hp started to increase in milk similarly and peaked at 36–44 hours. In serum, the concentration of Hp peaked at 60–68 hours and was twice as high as in milk. LBP concentrations in milk and serum started to increase after 12 hours and peaked at 36 hours, being higher in milk. The concentrations of acute phase proteins in serum and milk in the E. coli infection model were much higher than those recorded in experiments using Gram-positive pathogens, indicating the severe inflammation induced by E. coli. Conclusion Acute phase proteins would be useful parameters as mastitis indicators and to assess the severity of mastitis. If repeated experimental intramammary induction of the same animals

  18. RCSB PDB Mobile: iOS and Android mobile apps to provide data access and visualization to the RCSB Protein Data Bank

    PubMed Central

    Quinn, Gregory B.; Bi, Chunxiao; Christie, Cole H.; Pang, Kyle; Prlić, Andreas; Nakane, Takanori; Zardecki, Christine; Voigt, Maria; Berman, Helen M.; Rose, Peter W.

    2015-01-01

    Summary: The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) resource provides tools for query, analysis and visualization of the 3D structures in the PDB archive. As the mobile Web is starting to surpass desktop and laptop usage, scientists and educators are beginning to integrate mobile devices into their research and teaching. In response, we have developed the RCSB PDB Mobile app for the iOS and Android mobile platforms to enable fast and convenient access to RCSB PDB data and services. Using the app, users from the general public to expert researchers can quickly search and visualize biomolecules, and add personal annotations via the RCSB PDB’s integrated MyPDB service. Availability and implementation: RCSB PDB Mobile is freely available from the Apple App Store and Google Play (http://www.rcsb.org). Contact: pwrose@ucsd.edu PMID:25183487

  19. Early weaning alters the acute-phase reaction to an endotoxin challenge in beef calves.

    PubMed

    Carroll, J A; Arthington, J D; Chase, C C

    2009-12-01

    Previous research indicates that early weaning before shipment can reduce transportation-induced increases in acute-phase proteins (APP) and can increase feedlot performance in beef calves. These data suggest that the combination of weaning and transport stress may compromise the immune system of calves, thus hindering subsequent performance and health. Therefore, our objective was to determine if the innate immune response of early weaned calves (EW; 80 d of age) differed from normal-weaned calves (NW; 250 d of age) in response to an endotoxin challenge. Eighteen Brahman x Angus calves (8 and 10 EW and NW, respectively; 233 +/- 5 kg of BW) were used. Calves were maintained on pasture with supplement and then moved into individual pens for 1 wk of acclimation before the start of the study. Calves were fitted with an indwelling jugular catheter 1 d before LPS challenge (0 h; 1.0 microg/kg of BW, intravenously). Blood samples were collected at 30-min intervals from -2 to 8 h. Serum samples were stored at -80 degrees C until analyzed for cortisol, tumor necrosis factor-alpha (TNF), IL-1 beta, IL-6, interferon-gamma (IFN), ceruloplasmin, and haptoglobin. Whereas LPS increased serum cortisol (P or= 0.15) was observed. A weaning age x time interaction (P

  20. Identification of an acute-phase reactant in murine infections with Trypanosoma brucei.

    PubMed Central

    Shapiro, S Z; Black, S J

    1992-01-01

    A 42-kDa protein appeared at a much higher concentration in plasma from Trypanosoma brucei-resistant (C57BL/6) mice after infection than in plasma from trypanosome-susceptible (C3H/He) mice. This protein was purified by sequential steps of gel filtration, protein A-Sepharose affinity chromatography, isoelectric focusing, and ammonium sulfate precipitation. The purified protein was identified as a subunit of the acute-phase reactant haptoglobin. Causes of elevated plasma haptoglobin and its implications for resistance to trypanosomiasis are discussed. Images PMID:1500201

  1. Pan-Neuronal Expression of APL-1, an APP-Related Protein, Disrupts Olfactory, Gustatory, and Touch Plasticity in Caenorhabditis elegans

    PubMed Central

    Ewald, Collin Y.; Cheng, Ruby; Tolen, Lana; Shah, Vishal; Gillani, Aneela; Nasrin, Afsana

    2012-01-01

    Patients with Alzheimer's disease show age-related cognitive decline. Postmortem autopsy of their brains shows the presence of large numbers of senile plaques, whose major component is the β-amyloid peptide. The β-amyloid peptide is a cleavage product of the amyloid precursor protein (APP). In addition to the neurodegeneration associated with β-amyloid aggregation in Alzheimer's disease patients, mutations in APP in mammalian model organisms have also been shown to disrupt several behaviors independent of visible amyloid plaque formation. However, the pathways in which APP function are unknown and difficult to unravel in mammals. Here we show that pan-neuronal expression of APL-1, the Caenorhabditis elegans ortholog of APP, disrupts several behaviors, such as olfactory and gustatory learning behavior and touch habituation. These behaviors are mediated by distinct neural circuits, suggesting a broad impact of APL-1 on sensory plasticity in C. elegans. Furthermore, we found that disruption of these three behaviors requires activity of the TGFβ pathway and reduced activity of the insulin pathway. These results suggest pathways and molecular components that may underlie behavioral plasticity in mammals and in patients with Alzheimer's disease. PMID:22836251

  2. Expression of α1-acid glycoprotein and lipopolysaccharide binding protein in visceral and subcutaneous adipose tissue of dairy cattle.

    PubMed

    Rahman, Mizanur M; Lecchi, Cristina; Sauerwein, Helga; Mielenz, Manfred; Häußler, Susanne; Restelli, Laura; Giudice, Chiara; Ceciliani, Fabrizio

    2015-02-01

    Adipose tissue is an endocrine compartment that plays an important role in immune defence by producing and releasing a wide range of proteins, including acute phase proteins (APPs). The liver is the main organ of APP synthesis, although extrahepatic production has also been reported. In the present study, expression of two APPs in dairy cattle, lipopolysaccharide binding protein (LBP) and α1-acid glycoprotein (AGP), was determined in four visceral (pericardial, mesenteric, omental and retroperitoneal) and three subcutaneous (withers, tail head and sternum) adipose tissue depots. mRNA expression was evaluated using qualitative and quantitative PCR, protein profiles were assessed by Western blot analysis and cellular localisation was determined by immunohistochemistry. The presence of LBP and AGP was demonstrated at mRNA and protein levels in all seven adipose tissue depots. Expression of AGP and LBP suggests that they may have roles as local and systemic inflammatory adipokines. PMID:25542063

  3. Focally Elevated Creatine Detected in Amyloid Precursor Protein (APP) Transgenic Mice and Alzheimer Disease Brain Tissue

    SciTech Connect

    Gallant,M.; Rak, M.; Szeghalmi, A.; Del Bigio, M.; Westaway, D.; Yang, J.; Julian, R.; Gough, K.

    2006-01-01

    The creatine/phosphocreatine system, regulated by creatine kinase, plays an important role in maintaining energy balance in the brain. Energy metabolism and the function of creatine kinase are known to be affected in Alzheimer diseased brain and in cells exposed to the {beta}-amyloid peptide. We used infrared microspectroscopy to examine hippocampal, cortical, and caudal tissue from 21-89-week-old transgenic mice expressing doubly mutant (K670N/M671L and V717F) amyloid precursor protein and displaying robust pathology from an early age. Microcrystalline deposits of creatine, suggestive of perturbed energetic status, were detected by infrared microspectroscopy in all animals with advanced plaque pathology. Relatively large creatine deposits were also found in hippocampal sections from post-mortem Alzheimer diseased human brain, compared with hippocampus from non-demented brain. We therefore speculate that this molecule is a marker of the disease process.

  4. Induction of acute phase gene expression by brain irradiation

    SciTech Connect

    Hong, Ji-Hong |; Sun, Ji-Rong; Withers, H.R.

    1995-10-15

    To investigate the in vivo acute phase molecular response of the brain to ionizing radiation, C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1{alpha}, IL-1{beta}, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-{gamma}), tumor necrosis factors (TNF-{alpha} and TNF-{beta}), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), {alpha}1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. Levels of TNF-{alpha}, IL-1{beta}, ICAM-1, EB22/5.3, and to a lesser extent IL-1{alpha} and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances. 64 refs., 4 figs.

  5. [Targets of treatment in the acute phase of cerebral infarction].

    PubMed

    Tanaka, K; Fukuuchi, Y; Nogawa, S; Ito, D; Suzuki, S; Dembo, T; Kosakai, A

    2001-12-01

    In the acute phase of cerebral infarction, many experimental data suggest that free radicals including superoxide, hydroxy radical and nitric oxide are one of the most important factors to cause brain damage. We have clearly detected nitrotyrosine (a marker of endogenous production of peroxynitrite, which is readily produced from superoxide and nitric oxide) in neurons and intraparenchymal vascular walls during post-ischemic reperfusion. Free radical scavengers thus seem to be very promising tools of treatment, and one of them (edaravone) has recently been approved for clinical use in Japan. CREB (cyclic AMP response element binding protein) is a DNA-binding transcription factor, and its function is activated by phosphorylation of Ser133 residue. CREB plays important roles in neuronal development, synaptic plasticity and regeneration. We have found that phosphorylation of CREB is significantly and persistently increased in surviving neurons and oligodendrocytes in post-ischemic brain, while this phosphorylation is only transiently increased in neurons and oligodendrocytes which eventually die. These data suggest that CREB phosphorylation plays an important role in protection of ischemic brain tissue. Oligodendrocyte progenitor cells (OPC) remain abundant throughout the adult brain, and retain their ability to become not only mature oligodendrocytes, but also neurons. We have recently found that OPC are significantly activated and proliferate in the peri-infarct area at 1-2 weeks after ischemia, suggesting that OPC may be involved in the repair mechanisms of ischemic brain. Future targets of stroke treatment should include enhancement of intrinsic protection mechanisms such as CREB phosphorylation and activation of progenitors cells. PMID:12235793

  6. Axonal injury in young pediatric head trauma: a comparison study of β-amyloid precursor protein (β-APP) immunohistochemical staining in traumatic and nontraumatic deaths.

    PubMed

    Johnson, Michael W; Stoll, Lisa; Rubio, Ana; Troncoso, Juan; Pletnikova, Olga; Fowler, David R; Li, Ling

    2011-09-01

    We tested the independent utility of β-amyloid precursor protein (β-APP) immunohistochemical staining as evidence of brain trauma in the deaths of young children. Blinded reviewers retrospectively reviewed immunostained brain tissues from homicidal deaths, age-matched control cases without evidence of trauma, as well as cases of sudden infant death syndrome (SIDS). The reviewers correctly identified five of the seven cases with documented inflicted head trauma. However, one of seven age-matched control cases and one of 10 SIDS/sudden unexplained death in infancy (SUDI) cases demonstrated staining patterns similar to those seen in cases of inflicted trauma. We discuss these cases and the circumstances surrounding them with the intent to explain the difficulties associated with immunohistological interpretation of axonal injury. Although the utility of β-APP is quite powerful if not confounded by global hypoxic-ischemic injury, ultimately, β-APP studies should be only one piece of information in the determination of cause and manner of death.

  7. The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo.

    PubMed

    Cappai, Roberto; Cheng, Fang; Ciccotosto, Giuseppe D; Needham, B Elise; Masters, Colin L; Multhaup, Gerd; Fransson, Lars-Ake; Mani, Katrin

    2005-04-01

    Processing of the recycling proteoglycan glypican-1 involves the release of its heparan sulfate chains by copper ion- and nitric oxide-catalyzed ascorbate-triggered autodegradation. The Alzheimer disease amyloid precursor protein (APP) and its paralogue, the amyloid precursor-like protein 2 (APLP2), contain copper ion-, zinc ion-, and heparan sulfate-binding domains. We have investigated the possibility that APP and APLP2 regulate glypican-1 processing during endocytosis and recycling. By using cell-free biochemical experiments, confocal laser immunofluorescence microscopy, and flow cytometry of tissues and cells from wild-type and knock-out mice, we find that (a) APP and glypican-1 colocalize in perinuclear compartments of neuroblastoma cells, (b) ascorbate-triggered nitric oxidecatalyzed glypican-1 autodegradation is zinc ion-dependent in the same cells, (c) in cell-free experiments, APP but not APLP2 stimulates glypican-1 autodegradation in the presence of both Cu(II) and Zn(II) ions, whereas the Cu(I) form of APP and the Cu(II) and Cu(I) forms of APLP2 inhibit autodegradation, (d) in primary cortical neurons from APP or APLP2 knock-out mice, there is an increased nitric oxide-catalyzed degradation of heparan sulfate compared with brain tissue and neurons from wild-type mice, and (e) in growth-quiescent fibroblasts from APLP2 knock-out mice, but not from APP knock-out mice, there is also an increased heparan sulfate degradation. We propose that the rate of autoprocessing of glypican-1 is modulated by APP and APLP2 in neurons and by APLP2 in fibroblasts. These observation identify a functional relationship between the heparan sulfate and copper ion binding activities of APP/APLP2 in their modulation of the nitroxyl anion-catalyzed heparan sulfate degradation in glypican-1. PMID:15677459

  8. The acute phase inflammatory response to maximal exercise testing in children and young adults with sickle cell anaemia.

    PubMed

    Liem, Robert I; Onyejekwe, Kasiemobi; Olszewski, Marie; Nchekwube, Chisalu; Zaldivar, Frank P; Radom-Aizik, Shlomit; Rodeghier, Mark J; Thompson, Alexis A

    2015-12-01

    Although individuals with sickle cell anaemia (SCA) have elevated baseline inflammation and endothelial activation, the acute phase response to maximal exercise has not been evaluated among children with SCA. We measured the acute phase response to maximal exercise testing for soluble vascular cell adhesion molecule (sVCAM) as well as interleukin 6 (IL6), total white blood cell (WBC) count, C-reactive protein (CRP) and D-dimer in a cohort of children with SCA and matched controls at baseline, immediately after, and 30, 60 and 120 min following exercise. Despite higher baseline levels of all biomarkers except CRP, the acute phase response from baseline to immediately after exercise was significantly greater in subjects versus controls for CRP (2·1 vs. 0·2 mg/l, P = 0·02) and D-dimer (160 vs. 10 μg/l, P < 0·01) only. Similar between-group trends were observed over time for all biomarkers, including sVCAM, IL6, total WBC, CRP and D-dimer. Lower fitness, defined by peak oxygen consumption (VO2 ), was independently associated with greater acute phase responses to exercise for sVCAM. Our results suggest maximal exercise may not be associated with any greater escalation of endothelial activation or inflammation in SCA and provide preliminary biomarker evidence for the safety of brief, high-intensity physical exertion in children with SCA.

  9. Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response

    PubMed Central

    Rivory, L P; Slaviero, K A; Clarke, S J

    2002-01-01

    Inflammatory disease states (infection, arthritis) are associated with reduced drug oxidation by the cytochrome P450 3A system. Many chemotherapy agents are metabolised through this pathway, and disease may therefore influence inter-individual differences in drug pharmacokinetics. The purpose of this study was to assess cytochrome P450 3A function in patients with advanced cancer, and its relation to the acute-phase response. We evaluated hepatic cytochrome P450 3A function in 40 patients with advanced cancer using the erythromycin breath test. Both the traditional C20min measure and the recently proposed 1/TMAX values were estimated. The marker of acute-phase response, C-reactive protein and the pro-inflammatory cytokines IL-6, IL-1β, TNFα and IL-8 were measured in serum or plasma at baseline. Cancer patients with an acute phase response (C-reactive protein >10 mg l−1, n=26) had reduced metabolism as measured with the erythromycin breath test 1/TMAX (Kruskal–Wallis Anova, P=0.0062) as compared to controls (C-reactive protein ⩽10 mg l−1, n=14). Indeed, metabolism was significantly associated with C-reactive protein over the whole concentration range of this acute-phase marker (r=−0.64, Spearman Rank Correlation, P<0.00001). C-reactive protein serum levels were significantly correlated with those of IL-6 (Spearman coefficient=0.58, P<0.0003). The reduction in cytochrome P450 3A function with acute-phase reaction was independent of the tumour type and C-reactive protein elevation was associated with poor performance status. This indicates that the sub-group of cancer patients with significant acute-phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population. British Journal of Cancer (2002) 87, 277–280. doi:10.1038/sj.bjc.6600448 www.bjcancer.com © 2002 Cancer Research UK PMID:12177794

  10. Normal Caloric Responses during Acute Phase of Vestibular Neuritis

    PubMed Central

    Lee, Sun-Uk; Park, Seong-Ho; Kim, Hyo-Jung; Koo, Ja-Won

    2016-01-01

    Background and Purpose We report a novel finding of caloric conversion from normal responses into unilateral paresis during the acute phase of vestibular neuritis (VN). Methods We recruited 893 patients with a diagnosis of VN at Dizziness Clinic of Seoul National University Bundang Hospital from 2003 to 2014 after excluding 28 patients with isolated inferior divisional VN (n=14) and those without follow-up tests despite normal caloric responses initially (n=14). We retrospectively analyzed the neurotological findings in four (0.5%) of the patients who showed a conversion from initially normal caloric responses into unilateral paresis during the acute phase. Results In those four patients, the initial caloric tests were performed within 2 days of symptom onset, and conversion into unilateral caloric paresis was documented 1–4 days later. The clinical and laboratory findings during the initial evaluation were consistent with VN in all four patients except for normal findings in bedside head impulse tests in one of them. Conclusions Normal findings in caloric tests should be interpreted with caution during the acute phase of suspected VN. Follow-up evaluation should be considered when the findings of the initial caloric test are normal, but VN remains the most plausible diagnosis. PMID:26932259

  11. Molecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord Injury.

    PubMed

    Thakore, Nakul P; Samantaray, Supriti; Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A; Cox, April; Krause, James; Banik, Naren L

    2016-02-01

    To clarify the molecular changes of sublesional muscle in the acute phase of spinal cord injury (SCI), a moderately severe injury (40 g cm) was induced in the spinal cord (T10 vertebral level) of adult male Sprague-Dawley rats (injury) and compared with sham (laminectomy only). Rats were sacrificed at 48 h (acute) post injury, and gastrocnemius muscles were excised. Morphological examination revealed no significant changes in the muscle fiber diameter between the sham and injury rats. Western blot analyses performed on the visibly red, central portion of the gastrocnemius muscle showed significantly higher expression of muscle specific E3 ubiquitin ligases (muscle ring finger-1 and muscle atrophy f-box) and significantly lower expression of phosphorylated Akt-1/2/3 in the injury group compared to the sham group. Cyclooxygenase 2, tumor necrosis factor alpha (TNF-α), and caspase-1, also had a significantly higher expression in the injury group; although, the mRNA levels of TNF-α and IL-6 did not show any significant difference between the sham and injury groups. These results suggest activation of protein degradation, deactivation of protein synthesis, and development of inflammatory reaction occurring in the sublesional muscles in the acute phase of SCI before overt muscle atrophy is seen. PMID:26290268

  12. The Association between Platelet Count and Acute Phase Response in Chronic Spontaneous Urticaria

    PubMed Central

    Kasperska-Zając, Alicja; Grzanka, Alicja; Jarzab, Jerzy; Misiołek, Maciej; Wyszyńska-Chłap, Magdalena; Kasperski, Jacek; Machura, Edyta

    2014-01-01

    Background. The platelet parameters and C-reactive protein (CRP) are markers reflecting a systemic inflammatory response. Among those, CRP is one of the major proteins helpful in determination of severity/activity of chronic spontaneous urticaria (CSU). Aim. To determine relationships between platelet activation indices and serum concentration of CRP, the best marker of acute phase response, and their potential clinical use in CSU patients. Methods. Mean platelet volume (MPV), platelet distribution width (PDW), and platelet count as well as serum CRP concentration were measured in CSU patients, showing different degrees of urticarial severity, and in the healthy subjects. Results. No significant differences were found in MPV and PDW between CSU group and the healthy subjects. The platelet count was significantly higher in moderate-severe CSU than that of the controls and mild CSU patients. Serum CRP concentrations were significantly higher in CSU patients as compared with the healthy subjects and significantly correlated with the platelet count in CSU patients. Conclusions. Acute phase response in CSU is associated with the increased number of circulating platelets in patients with more severe symptoms. It seems that simple determination of platelet size indices is not a reliable indicator of CSU severity/activity. PMID:25025065

  13. The use of liquid chromatography tandem mass spectrometry to detect proteins in saliva from horses with and without systemic inflammation.

    PubMed

    Jacobsen, Stine; Top Adler, Ditte Marie; Bundgaard, Louise; Sørensen, Mette Aamand; Andersen, Pia Haubro; Bendixen, Emøke

    2014-12-01

    The objective of the study was to assess global expression of proteins in equine saliva using liquid chromatography tandem mass spectrometry (LC-MS/MS). Saliva was obtained from seven horses with and six horses without evidence of systemic inflammatory disease. Tryptic peptides from saliva were analysed by LC-MS/MS. Of 195 unique proteins identified, 57 were detected only in saliva samples from horses with systemic inflammation (in two to six of the seven horses). Among the differentially expressed proteins were several acute phase proteins (APPs) such as serum amyloid A, fibrinogen, haptoglobin, and alpha1-acid glycoprotein. The study is the first to describe detection of inflammatory proteins in horse saliva. The proteins detected were similar to those described in saliva from cattle, small ruminants and pigs. Detection of APPs in horses with systemic inflammation suggests that saliva may be used for non-invasive disease monitoring in horses as in humans, pigs and dogs. PMID:25296850

  14. APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

    PubMed Central

    Moore, Steven; Evans, Lewis D.B.; Andersson, Therese; Portelius, Erik; Smith, James; Dias, Tatyana B.; Saurat, Nathalie; McGlade, Amelia; Kirwan, Peter; Blennow, Kaj; Hardy, John; Zetterberg, Henrik; Livesey, Frederick J.

    2015-01-01

    Summary Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. PMID:25921538

  15. Alcadein Cleavages by Amyloid β-Precursor Protein (APP) α- and γ-Secretases Generate Small Peptides, p3-Alcs, Indicating Alzheimer Disease-related γ-Secretase Dysfunction*

    PubMed Central

    Hata, Saori; Fujishige, Sayaka; Araki, Yoichi; Kato, Naoko; Araseki, Masahiko; Nishimura, Masaki; Hartmann, Dieter; Saftig, Paul; Fahrenholz, Falk; Taniguchi, Miyako; Urakami, Katsuya; Akatsu, Hiroyasu; Martins, Ralph N.; Yamamoto, Kazuo; Maeda, Masahiro; Yamamoto, Tohru; Nakaya, Tadashi; Gandy, Sam; Suzuki, Toshiharu

    2009-01-01

    Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins, designated Alcα, Alcβ, and Alcγ. The Alcs express in neurons dominantly and largely colocalize with the Alzheimer amyloid precursor protein (APP) in the brain. Alcs and APP show an identical function as a cargo receptor of kinesin-1. Moreover, proteolytic processing of Alc proteins appears highly similar to that of APP. We found that APP α-secretases ADAM 10 and ADAM 17 primarily cleave Alc proteins and trigger the subsequent secondary intramembranous cleavage of Alc C-terminal fragments by a presenilin-dependent γ-secretase complex, thereby generating “APP p3-like” and non-aggregative Alc peptides (p3-Alcs). We determined the complete amino acid sequence of p3-Alcα, p3-Alcβ, and p3-Alcγ, whose major species comprise 35, 37, and 31 amino acids, respectively, in human cerebrospinal fluid. We demonstrate here that variant p3-Alc C termini are modulated by FAD-linked presenilin 1 mutations increasing minor β-amyloid species Aβ42, and these mutations alter the level of minor p3-Alc species. However, the magnitudes of C-terminal alteration of p3-Alcα, p3-Alcβ, and p3-Alcγ were not equivalent, suggesting that one type of γ-secretase dysfunction does not appear in the phenotype equivalently in the cleavage of type I membrane proteins. Because these C-terminal alterations are detectable in human cerebrospinal fluid, the use of a substrate panel, including Alcs and APP, may be effective to detect γ-secretase dysfunction in the prepathogenic state of Alzheimer disease subjects. PMID:19864413

  16. Understanding Mobile Apps

    MedlinePlus

    ... a device, you’re committed to using the operating system and the type of apps that go with it. The Android, Apple, Microsoft and BlackBerry mobile operating systems have app stores online where you can look ...

  17. Liver receptor homolog 1 is a negative regulator of the hepatic acute-phase response.

    PubMed

    Venteclef, Nicolas; Smith, Jason C; Goodwin, Bryan; Delerive, Philippe

    2006-09-01

    The orphan nuclear receptor liver receptor homolog 1 (LRH-1) has been reported to play an important role in bile acid biosynthesis and reverse cholesterol transport. Here, we show that LRH-1 is a key player in the control of the hepatic acute-phase response. Ectopic expression of LRH-1 with adenovirus resulted in strong inhibition of both interleukin-6 (IL-6)- and IL-1beta-stimulated haptoglobin, serum amyloid A, and fibrinogen beta gene expression in hepatocytes. Furthermore, induction of the hepatic inflammatory response was significantly exacerbated in HepG2 cells expressing short hairpin RNA targeting LRH-1 expression. Moreover, transient-transfection experiments and electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that LRH-1 regulates this cytokine-elicited inflammatory response by, at least in part, antagonizing the CCAAT/enhancer binding protein beta signaling pathway. Finally, we show, by using LRH-1 heterozygous mice, that LRH-1 is involved in the control of the inflammatory response at the hepatic level in vivo. Taken together, our results outline an unexpected role for LRH-1 in the modulation of the hepatic acute-phase response.

  18. Biosynthesis and secretion of alpha 1 acute-phase globulin in primary cultures of rat hepatocytes.

    PubMed

    Bauer, J; Kurdowska, A; Tran-Thi, T A; Budek, W; Koj, A; Decker, K; Heinrich, P C

    1985-01-15

    Experimental inflammation in rats led to a sevenfold increase in serum levels of alpha 1 acute-phase globulin. This increase is correlated with elevated levels of translatable mRNA for alpha 1 acute-phase globulin in the liver. Biosynthesis and secretion of alpha 1 acute-phase globulin were studied in rat hepatocyte primary cultures. An intracellular form of alpha 1 acute-phase globulin with an apparent relative molecular mass of 63 500 and a secreted form of 68 000 were found. The intracellular form of alpha 1 acute-phase globulin could be deglycosylated by endoglucosaminidase H treatment indicating that its oligosaccharide chains were of the high-mannose type. The secreted form of alpha 1 acute-phase globulin was not sensitive to endoglucosaminidase H, but was susceptible to the action of sialidase reflecting carbohydrate side-chains of the complex type. Pulse-chase experiments revealed a precursor-product relationship for the high-mannose and the complex type alpha 1 acute-phase globulin. In the hepatocyte medium newly synthesized alpha 1 acute-phase globulin was detected 30 min after the pulse. Unglycosylated alpha 1 acute-phase globulin was found in the cells as well as in the medium when the transfer of oligosaccharide chains onto the polypeptide chains was blocked by tunicamycin. Tunicamycin led to a marked delay in alpha 1 acute-phase globulin secretion. PMID:2578391

  19. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    SciTech Connect

    Shannahan, Jonathan H.; Alzate, Oscar; Winnik, Witold M.; Andrews, Debora; Schladweiler, Mette C.; Ghio, Andrew J.; Gavett, Stephen H.; Kodavanti, Urmila P.

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  20. APP induces neuronal apoptosis through APP-BP1-mediated downregulation of beta-catenin.

    PubMed

    Chen, Y Z

    2004-07-01

    Alzheimer's disease (AD) is a neurodegenerative disease associated with progressive dementia. This mini-review focuses on how the amyloid precursor protein (APP) plays a central role in AD and Down syndrome as the regulator of the APP-BP1/hUba3 activated neddylation pathway. It is argued that the physiological function of APP is to downregulate the level of beta-catenin. However, this APP function is abnormally amplified in patients with familial AD (FAD) mutations in APP and presenilins, resulting in the hyperactivation of neddylation and the decrease of beta-catenin below a threshold level. Evidence in the literature is summarized to show that dysfunction of APP in downregulating beta-catenin may underlie the mechanism of neuronal death in AD and Down syndrome. PMID:15192323

  1. A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer’s disease

    PubMed Central

    Kang, Jing

    2016-01-01

    A small molecule named ISRIB has recently been described to enhance memory in rodents. In this study we aimed to test whether ISRIB would reverse learning and memory deficits in the J20 mouse model of human amyloid precursor protein (hAPP) overexpression, a model that simulates many aspects of Alzheimer’s disease in which memory deficits are a hallmark feature. We did not observe a significant rescue effect with ISRIB treatment on spatial learning and memory as assessed in the Morris water maze in J20 mice. We also did not observe a significant enhancement of spatial learning or memory in nontransgenic mice with ISRIB treatment, although a trend emerged for memory enhancement in one cohort of mice. Future preclinical studies with ISRIB would benefit from additional robust markers of target engagement in the brain. PMID:27781164

  2. Particle-Induced Pulmonary Acute Phase Response Correlates with Neutrophil Influx Linking Inhaled Particles and Cardiovascular Risk

    PubMed Central

    Saber, Anne Thoustrup; Lamson, Jacob Stuart; Jacobsen, Nicklas Raun; Ravn-Haren, Gitte; Hougaard, Karin Sørig; Nyendi, Allen Njimeri; Wahlberg, Pia; Madsen, Anne Mette; Jackson, Petra; Wallin, Håkan; Vogel, Ulla

    2013-01-01

    Background Particulate air pollution is associated with cardiovascular disease. Acute phase response is causally linked to cardiovascular disease. Here, we propose that particle-induced pulmonary acute phase response provides an underlying mechanism for particle-induced cardiovascular risk. Methods We analysed the mRNA expression of Serum Amyloid A (Saa3) in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes), diesel exhaust particles and airborne dust collected at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes. Results Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points. Conclusions Pulmonary acute phase response may constitute a direct link between particle inhalation and risk of cardiovascular disease. We propose that the particle-induced pulmonary acute phase response may predict risk for cardiovascular disease. PMID:23894396

  3. Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

    PubMed Central

    Thomsen, Karen Louise; Møller, Holger Jon; Graversen, Jonas Heilskov; Magnusson, Nils E; Moestrup, Søren K; Vilstrup, Hendrik; Grønbæk, Henning

    2016-01-01

    AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate (0.02 mg/kg) or free dexamethasone (0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide (LPS) (2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6) 2 h post-LPS and liver mRNAs and serum concentrations of the rat acute phase protein α-2-macroglobulin (α-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid effects. RESULTS: The conjugate halved the α-2-M liver mRNA (3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein (201 ± 48 μg/mL vs 389 ± 67 μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver mRNA or serum levels of α-2-M. Also, the conjugate reduced TNF-α (7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6 (15685 ± 3779 pg/mL vs 25715 ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight (421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other group. CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo. PMID:27330681

  4. [The nutrition of acute phase in patients with metabolic syndrome].

    PubMed

    Tsutsumi, Rie; Sebe, Mayu

    2016-03-01

    In this session, we describe the acute phase in patients with metabolic syndrome from two sides; acute disease that occurs higher in patients with metabolic syndrome such as colonary heart disease and stroke, and acute aggravation of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome. The electrolyte imbalance is frequently detected in critical ill patients. It is reported that the extreme abnormalities of ionized calcium concentrations are independent predictors of mortality. In addition, from clinical database MIMIC-Ⅱ,calcium supplementation improves clinical outcome in intensive care unit patients. Although metabolic syndrome; lifestyle-related disease, is a chronic disease, the possibility of falling into acute disease by having it becomes very high and improvement of electrolyte imbalance, especially hypocalcaemia is expected to effective on clinical outcome. PMID:26923986

  5. [The nutrition of acute phase in patients with metabolic syndrome].

    PubMed

    Tsutsumi, Rie; Sebe, Mayu

    2016-03-01

    In this session, we describe the acute phase in patients with metabolic syndrome from two sides; acute disease that occurs higher in patients with metabolic syndrome such as colonary heart disease and stroke, and acute aggravation of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome. The electrolyte imbalance is frequently detected in critical ill patients. It is reported that the extreme abnormalities of ionized calcium concentrations are independent predictors of mortality. In addition, from clinical database MIMIC-Ⅱ,calcium supplementation improves clinical outcome in intensive care unit patients. Although metabolic syndrome; lifestyle-related disease, is a chronic disease, the possibility of falling into acute disease by having it becomes very high and improvement of electrolyte imbalance, especially hypocalcaemia is expected to effective on clinical outcome.

  6. Molecular and cellular mechanisms used in the acute phase of stimulated steroidogenesis.

    PubMed

    Thomson, M

    1998-01-01

    Steroidogenic tissue can respond almost immediately to a stimulatory hormonal stimuli. Recent findings are shedding light on the molecular and cellular mechanisms that are used to synthesize and export steroid hormones in the acute phase of stimulation. In addition to utilising the cAMP intracellular messenger system to convey a stimulatory message, steroidogenic cells may employ the protein kinase C, arachidonic acid, tyrosine phosphate and nitrous oxide systems. It has been proposed that cholesterol laden vesicles travel along a network of intermediate filaments to reach the mitochondria. Cholesterol may then translocate from the outer mitochondrial membrane to the inner via sites of contact between the two membranes. These contact sites may be composed of protein bridges which include the constituents, porin, the benzodiazepine receptor and GTP binding proteins. Cholesterol is transported through the contact sites to the inner membrane and on reaching cytochrome P450 side chain cleavage (P450scc), cholesterol is converted to pregnenolone. Pregnenolone is in turn converted to a range of steroid hormones via enzyme casades. GTP binding proteins may regulate the contact site between the inner and outer membranes and thereby modulate cholesterol flux to P450scc. In the adrenal and gonads the rate that cholesterol traverses the contact point to reach the inner membrane is accelerated by the steroidogenic acute regulatory protein. Newly synthesized steroid hormones are transported to the cell periphery for export via a mechanism that may utilise an ion exchange protein.

  7. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    PubMed Central

    Saber, Anne T; Halappanavar, Sabina; Folkmann, Janne K; Bornholdt, Jette; Boisen, Anne Mette Z; Møller, Peter; Williams, Andrew; Yauk, Carole; Vogel, Ulla; Loft, Steffen; Wallin, Håkan

    2009-01-01

    Background Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP) and serum amyloid A (SAA) in humans. In this study we test the hypothesis that diesel exhaust particles (DEP) – or carbon black (CB)-induced lung inflammation initiates an acute phase response in the liver. Results Mice were exposed to filtered air, 20 mg/m3 DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation., Arch. Toxicol. 79 (2005) 177–182). As a positive control for the induction of an acute phase response, mice were exposed to 12.5 mg/kg of lipopolysaccharide (LPS) intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic mRNA expression of acute phase proteins, serum amyloid P (Sap) (the murine homologue of Crp) and Saa1 and Saa3. While significant increases in the hepatic expression of Sap, Saa1 and Saa3 were observed in response to LPS, their levels did not change in response to DEP or CB. In a comprehensive search for markers of an acute phase response, we analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine) proteinase inhibitor, clade A, member 3C, apolipoprotein E and transmembrane emp24 domain containing 3) responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT-PCR. Conclusion Our findings

  8. Insight into inhibition of the human amyloid beta protein precursor (APP: PDB ID ) using (E)-N-(pyridin-2-ylmethylene)arylamine (LR) models: structure elucidation of a family of ZnX2-LR complexes.

    PubMed

    Basu Baul, Tushar S; Kundu, Sajal; Singh, Palwinder; Shaveta; Guedes da Silva, M Fátima C

    2015-02-01

    The amyloid beta precursor protein (APP) and its neurotoxic cleavage product amyloid beta (Aβ) are a cause of Alzheimer's disease and appear essential for neuronal development and cell homeostasis. Proteolytic processing of APP is influenced by metal ions and protein ligands, however the structural and functional mechanism of APP regulation is not known so far. In this context, molecular modeling studies were performed to understand the molecular behavior of (E)-N-(pyridin-2-ylmethylene)arylamines (LR) with an E2 domain of the APP in its complex with zinc (APP; PDB ID: ). Docking results indeed confirmed that the LR interacts with Zn in the binding site of the protein between two α-helical chains. In view of these findings, LR was further investigated for complexation reactions with Zn(2+) in order to establish the structural models in solution and in the solid state. Five new Zn(2+) complexes of compositions viz. [Zn(Br)2(L2-Me)] (), [Zn(Br)2(L2-OMe)] (), [Zn(i)2(L2-OMe)] (), [Zn(NO3)2(L2-OMe)(H2O)] () and [Zn(L4-Me)2(H2O)2](NO3)2 () were synthesized and their structures were ascertained by microanalysis, IR and (1)H NMR spectroscopy, and single-crystal X-ray diffraction. The zinc atom in complex exhibits a distorted tetrahedral geometry while the crystal structures of complexes and show distorted square pyramidal geometries. The zinc cation in and has an octahedral coordination environment, but in the zinc coordination geometry is less distorted. The Zn(ii) cations take part in one ( and ) or two () 5-membered metallacycles imposed by the NN or NNO chelation modes of LR. The significant intermolecular ππ interactions are also discussed.

  9. Decreased expression of hepatocyte nuclear factor 3 alpha during the acute-phase response influences transthyretin gene transcription.

    PubMed Central

    Qian, X; Samadani, U; Porcella, A; Costa, R H

    1995-01-01

    Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta, and gamma) are known to regulate the transcription of numerous liver-specific genes. The HNF-3 proteins bind to DNA as monomers through a winged-helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic fork head (fkh) protein. We have previously characterized a strong-affinity HNF-3S site in the transthyretin (TTR) promoter region which is essential for expression in human hepatoma (HepG2) cells. In the current study, we identify an activating protein 1 (AP-1) site which partially overlaps the HNF-3S sequence in the TTR promoter. We show that in HepG2 cells the AP-1 sequence confers 12-O-tetradecanoylphorbol-13-acetate inducibility to the TTR promoter and contributes to normal TTR transcriptional activity. We also demonstrate that the HNF-3 proteins and AP-1 bind independently to the TTR AP-1-HNF-3 site, and cotransfection experiments suggest that they do not cooperate to activate an AP-1-HNF-3 reporter construct. In addition, 12-O-tetradecanoylphorbol-13-acetate exposure of HepG2 cells results in a reciprocal decrease in HNF-3 alpha and -3 gamma expression which may facilitate interaction of AP-1 with the TTR AP-1-HNF-3 site. In order to explore the role of HNF-3 in the liver, we have examined expression patterns of TTR and HNF-3 during the acute-phase response and liver regeneration. Partial hepatectomy produced minimal fluctuation in HNF-3 and TTR expression, suggesting that HNF-3 expression is not influenced by proliferative signals induced during liver regeneration. In acute-phase livers, we observed a dramatic reduction in HNF-3 alpha expression which correlates with a decrease in the expression of its target gene, the TTR gene. Furthermore, consistent with previous studies, the acute-phase livers are induced for c-jun but not c-fos expression. We propose that the reduction in TTR gene expression during the acute phase is likely due

  10. Apps for Ancient Civilizations

    ERIC Educational Resources Information Center

    Thompson, Stephanie

    2011-01-01

    This project incorporates technology and a historical emphasis on science drawn from ancient civilizations to promote a greater understanding of conceptual science. In the Apps for Ancient Civilizations project, students investigate an ancient culture to discover how people might have used science and math smartphone apps to make their lives…

  11. Mobile Apps for Librarians

    ERIC Educational Resources Information Center

    Power, June L.

    2013-01-01

    In an increasing mobile environment, library and reading-related activities often take place on a phone or tablet device. Not only does this mean that library Web sites must keep mobile navigability in mind, but also develop and utilize apps that allow patrons to interact with information and with libraries. While apps do not serve every purpose,…

  12. RFLP analysis for APP 717 mutations associated with Alzheimer's disease.

    PubMed

    Zeldenrust, S R; Murrell, J; Farlow, M; Ghetti, B; Roses, A D; Benson, M D

    1993-06-01

    Familial Alzheimer's disease (FAD) has been shown to be associated with three distinct point mutations within the same codon of the amyloid precursor protein (APP) gene. The mutation identified in the Indiana kindred is a G-->T transversion at the first position of the codon for amino acid 717, resulting in a substitution of phenylalanine for valine in the APP protein. Screening of persons at risk for the APP Phe-717 mutation using a variation of the polymerase chain reaction identified nine positives among 34 tested. In addition, DNA from 145 FAD subjects were tested for the three known APP 717 mutations.

  13. Effects of the Neurac® technique in patients with acute-phase subacromial impingement syndrome

    PubMed Central

    Kim, Soo-Yong; Kang, Min-Hyeok; Lee, Dong-Kyu; Oh, Jae-Seop

    2015-01-01

    [Purpose] This study investigated the effects of the Neurac technique on shoulder pain, function, and range of motion in patients with acute-phase subacromial impingement syndrome. [Subjects] Thirteen patients (seven females and six males) with acute-phase subacromial impingement syndrome participated in this study. [Methods] Shoulder pain, function, and range of motion were assessed before and after the application of the Neurac technique. [Results] Pain and function scores were significantly lower after than before the Neurac intervention. Shoulder range of motion was significantly greater after Neurac intervention than before it. [Conclusion] The Neurac technique is a useful intervention for patients with acute-phase subacromial impingement syndrome. PMID:26157230

  14. Apps for hearing healthcare.

    PubMed

    Paglialonga, Alessia; Tognola, Gabriella; Pinciroli, Francesco

    2015-01-01

    The hearing healthcare scenario is rapidly evolving due to the pervasive use of m-Health solutions, in particular mobile apps. This brings along significant advantages and opportunities (e.g., accessibility, affordability, personalized healthcare, patient empowerment) as well as significant potential risks and threats (e.g., safety, misuse, quality issues, privacy). Our research aims at the identification and assessment of apps in the hearing healthcare domain. In this article we present an overview of the current availability, variety, and penetration of hearing-related apps.

  15. RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing

    PubMed Central

    2012-01-01

    Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimer's disease (AD) brain, is produced from amyloid precursor protein (APP) by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB) domains, including Dab (gene: DAB) and Numb (gene: NUMB), can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells) or APP-C99 (H4-APP-C99 cells) increased levels of APP-C-terminal fragments (APP-CTFs) and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of AD. The notion of attenuating γ-secretase cleavage of APP via the APP adaptor proteins, Dab and Numb, is particularly attractive with regard to therapeutic potential, given that side effects of γ-secretase inhibition owing to impaired proteolysis of other γ-secretase substrates, e.g. Notch, might be avoided. PMID:23211096

  16. Biochemical investigations after burning injury: complement system, protease-antiprotease balance and acute-phase reactants.

    PubMed

    Faymonville, M E; Micheels, J; Bodson, L; Jacquemin, D; Lamy, M; Adam, J; Duchateau, J

    1987-02-01

    Seventeen burned patients were investigated--Group I (n=10) with a mean burned area expressed as unit burn standard (UBS) of 69 +/- 24 and Group II (n = 7) with a mean UBS of 23 +/- 8. Blood samples were collected immediately after admission, 6-12 h after injury, during the morning and evening of day 1, and then daily for 2 weeks. This prospective study demonstrated complement activation in vivo in all burned patients, measured by C3d/C3 ratio index which was not related to the extent of the burned surface. A significant protease-antiprotease imbalance, correlated to the severity of burns, was found, leukocyte elastase was increased throughout the observation period, alpha 2-macroglobulin drastically decreased in severely burned patients, and alpha 1-proteinase inhibitor promptly decreased below the normal level in patients with more than 40 UBS. Finally, there was a delayed but then persistent acute-phase reactant protein response involving C-reactive protein, haptoglobin and alpha 1-acid glycoprotein, the concentrations of which reached a plateau on days 6 or 7.

  17. International Space Apps Challenge

    NASA Video Gallery

    During the 2013 Space Apps Challenge, space enthusiasts with diverse backgrounds gathered April 20-21 for a collaborative, global problem-solving effort. Held at Kennedy Space Center Visitor Comple...

  18. Stop, Breathe & Think app.

    PubMed

    Shaw, Natalie

    2014-07-15

    The Stop, Breathe & Think app is free, thanks to underwriting from Tools for Peace, the non-profit organisation that teaches people of all ages how to develop and apply kindness and compassion in their daily lives.

  19. Apps I Have Loved

    ERIC Educational Resources Information Center

    Schaffhauser, Dian

    2011-01-01

    According to a March estimate from Distimo, there were 653,614 apps in the iPhone, Android, iPad, BlackBerry, and Windows Mobile stores alone. So, is it any wonder that these busy people have found a few that come in handy on the job? Mobile apps are as indispensable to district IT executives as they are becoming in the classroom--for professional…

  20. Altered Arginine Metabolism in Cells Transfected with Human Wild-Type Beta Amyloid Precursor ProteinAPP).

    PubMed

    Jęśko, Henryk; Wilkaniec, Anna; Cieślik, Magdalena; Hilgier, Wojciech; Gąssowska, Magdalena; Lukiw, Walter J; Adamczyk, Agata

    2016-01-01

    Alterations of enzymes linked to arginine metabolism have been recently implicated in Alzheimer's disease (AD). Despite strong association of arginine changes with nitric oxide (NO) pathway, the impact of amyloid β (Aβ) peptides on arginine degradation and re-synthesis is unknown. In the present study we compared expression levels of arginases (ARG1, ARG2), neuronal, endothelial and inducible NO synthase isoforms (NNOS, ENOS, INOS), enzymes that metabolize arginine or resynthesize it from citrulline and the levels of corresponding amino acids in rat pheochromocytoma (PC12) cells overexpressing human Aβ precursor protein (APPwt cells). Moreover, we investigated the changes in miRNAs responsible for modulation of arginine metabolism in AD brains. Real-time PCR analysis revealed in APPwt cells significant decreases of ARG1 and ARG2 which are responsible for lysing arginine into ornithine and urea; this reduction was followed by significantly lower enzyme activity. NNOS and ENOS mRNAs were elevated in APPwt cells while iNOS was undetectable in both cell lines. The expression of argininosuccinate synthase (ASS) that metabolizes citrulline was down-regulated without changes in argininosuccinate lyase (ASL). Ornithine decarboxylase (ODC), which decarboxylates ornithine to form putrescine was also reduced. Arginine, the substrate for both arginases and NOS, was unchanged in APPwt cells. However, citrulline concentration was significantly higher. Elevated miRNA-9 and miRNA-128a found in AD brain tissues might modulate the expression of ASS and NOS, respectively. Our results indicate that Aβ affects arginine metabolism and this influence might have important role in the pathomechanism of AD.

  1. Altered Arginine Metabolism in Cells Transfected with Human Wild-Type Beta Amyloid Precursor ProteinAPP).

    PubMed

    Jęśko, Henryk; Wilkaniec, Anna; Cieślik, Magdalena; Hilgier, Wojciech; Gąssowska, Magdalena; Lukiw, Walter J; Adamczyk, Agata

    2016-01-01

    Alterations of enzymes linked to arginine metabolism have been recently implicated in Alzheimer's disease (AD). Despite strong association of arginine changes with nitric oxide (NO) pathway, the impact of amyloid β (Aβ) peptides on arginine degradation and re-synthesis is unknown. In the present study we compared expression levels of arginases (ARG1, ARG2), neuronal, endothelial and inducible NO synthase isoforms (NNOS, ENOS, INOS), enzymes that metabolize arginine or resynthesize it from citrulline and the levels of corresponding amino acids in rat pheochromocytoma (PC12) cells overexpressing human Aβ precursor protein (APPwt cells). Moreover, we investigated the changes in miRNAs responsible for modulation of arginine metabolism in AD brains. Real-time PCR analysis revealed in APPwt cells significant decreases of ARG1 and ARG2 which are responsible for lysing arginine into ornithine and urea; this reduction was followed by significantly lower enzyme activity. NNOS and ENOS mRNAs were elevated in APPwt cells while iNOS was undetectable in both cell lines. The expression of argininosuccinate synthase (ASS) that metabolizes citrulline was down-regulated without changes in argininosuccinate lyase (ASL). Ornithine decarboxylase (ODC), which decarboxylates ornithine to form putrescine was also reduced. Arginine, the substrate for both arginases and NOS, was unchanged in APPwt cells. However, citrulline concentration was significantly higher. Elevated miRNA-9 and miRNA-128a found in AD brain tissues might modulate the expression of ASS and NOS, respectively. Our results indicate that Aβ affects arginine metabolism and this influence might have important role in the pathomechanism of AD. PMID:26971935

  2. [Procalcitonin. A new marker for acute phase reaction in acute pancreatitis].

    PubMed

    Bertsch, T; Richter, A; Hofheinz, H; Böhm, C; Hartel, M; Aufenanger, J

    1997-01-01

    Procalcitonin is a protein which is found in elevated concentrations in the blood circulation during systemic bacterial, fungal or protozoal infection. In contrast to classical acute-phase proteins like C-reactive protein or interleukin-6, it is not elevated after operative trauma. In this paper we present current opinions on the assumed induction mechanisms of the protein by cytokines and endotoxin. Furthermore, the clinical value for early detection of systemic infections in abdominal and transplantation surgery is demonstrated by examples from the literature. Our investigation shows that eight patients with necrotizing pancreatitis had a PCT mean value of 6.9 ng/ml on the day of admission. Seven patients with edematous pancreatitis had only a PCT mean value of 0.69 ng/ml. Despite these differences in the mean values, a significant difference between the normal value and the mean value of the group with necrotizing pancreatitis or edematous pancreatitis was not observed due to the wide range of PCT levels in the group of patients with necrotizing pancreatitis. The fact that only a few of the patients had a superinfected necrosis with systemic evasion of bacterias or their toxins may be the reason for this wide range. We suggest that a discrimination between superinfected necrotizing or sterile pancreatitis and edematous pancreatitis by PCT could be possible but more extensive studies with microbiological examination of the necrotic material are required to recognize the subgroups and to establish the real diagnostic efficiency of PCT in clinical practice, especially in the prediction of the outcome of acute pancreatitis.

  3. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    PubMed

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-05-23

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms.

  4. Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression.

    PubMed

    Michalovicz, Lindsay T; Konat, Gregory W

    2014-03-01

    We have previously shown that peripherally restricted acute phase response (APR) elicited by intraperitoneal (i.p.) injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to excitotoxic insult as seen from profoundly exacerbated kainic acid (KA)-induced seizures. In the present study, we found that this hypersusceptibility was protracted for up to 72 h. RT-PCR profiling of hippocampal gene expression revealed rapid upregulation of 23 genes encoding cytokines, chemokines and chemokine receptors generally within 6 h after PIC challenge. The expression of most of these genes decreased by 24 h. However, two chemokine genes, i.e., Ccl19 and Cxcl13 genes, as well as two chemokine receptor genes, Ccr1 and Ccr7, remained upregulated for 72 h suggesting their possible involvement in the induction and sustenance of seizure hypersusceptibility. Also, 12 genes encoding proteins related to glutamatergic and GABAergic neurotransmission featured initial upregulation or downregulation followed by gradual normalization. The upregulation of the Gabrr3 gene remained upregulated at 72 h, congruent with its plausible role in the hypersusceptible phenotype. Moreover, the expression of ten microRNAs (miRs) was rapidly affected by PIC challenge, but their levels generally exhibited oscillating profiles over the time course of seizure hypersusceptibility. These results indicate that protracted seizure susceptibility following peripheral APR is associated with a robust polygenic response in the hippocampus. PMID:24363211

  5. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    PubMed

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-01-01

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms. PMID:27323085

  6. The relationship between visfatin, liver inflammation, and acute phase reactants in chronic viral hepatitis B.

    PubMed

    Yüksel, Enver; Akbal, Erdem; Koçak, Erdem; Akyürek, Ömer; Köklü, Seyfettin; Ekiz, Fuat; Yılmaz, Barış

    2016-09-01

    Chronic viral hepatitis B (CHB) is an important cause of morbidity and mortality. Adipokine stimulation might play an important role in the pathogenesis of chronic inflammation. The aim of this study was to evaluate serum visfatin concentrations and the relationship between visfatin, fibrosis, liver inflammation, and acute phase reactants in CHB patients.The sampling universe of the study consisted of 41 CHB patients and 25 healthy controls. All patients had positive hepatitis B surface antigen (Hepatitis e antigen (HBeAg) positive n: 7, n: 34 HBeAg negative) for at least 6 months and detectable serum HBV DNA. Serum visfatin concentrations were significantly higher in the CHB patients [18.0 ± 10.9 ng dL(-1)] than in the healthy controls [9.4 ± 1.6 ng dL(-1)] [P < 0.001]. On the other hand, fibrinogen and haptoglobin concentrations were significantly lower in CHB patients. A strong negative correlation was observed between serum visfatin concentration, haptoglobin, and fibrinogen levels; however, there was no significant correlation between visfatin, glucose, alanine aminotransferase, aspartate aminotransferase, BMI, Knodell score, fibrosis score, hepatitis B virus DNA, sedimentation, and C-reactive protein. Visfatin concentrations were elevated and visfatin was negatively correlated with haptoglobin and fibrinogen levels in CHB patients.

  7. Reassessment of HIV-1 Acute Phase Infectivity: Accounting for Heterogeneity and Study Design with Simulated Cohorts

    PubMed Central

    Bellan, Steve E.; Dushoff, Jonathan; Galvani, Alison P.; Meyers, Lauren Ancel

    2015-01-01

    Background The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk. Methods and Findings We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (dacute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0

  8. Regulation of global gene expression and cell proliferation by APP

    PubMed Central

    Wu, Yili; Zhang, Si; Xu, Qin; Zou, Haiyan; Zhou, Weihui; Cai, Fang; Li, Tingyu; Song, Weihong

    2016-01-01

    Down syndrome (DS), caused by trisomy of chromosome 21, is one of the most common genetic disorders. Patients with DS display growth retardation and inevitably develop characteristic Alzheimer’s disease (AD) neuropathology, including neurofibrillary tangles and neuritic plaques. The expression of amyloid precursor protein (APP) is increased in both DS and AD patients. To reveal the function of APP and elucidate the pathogenic role of increased APP expression in DS and AD, we performed gene expression profiling using microarray method in human cells overexpressing APP. A set of genes are significantly altered, which are involved in cell cycle, cell proliferation and p53 signaling. We found that overexpression of APP inhibits cell proliferation. Furthermore, we confirmed that the downregulation of two validated genes, PSMA5 and PSMB7, inhibits cell proliferation, suggesting that the downregulation of PSMA5 and PSMB7 is involved in APP-induced cell proliferation impairment. Taken together, this study suggests that APP regulates global gene expression and increased APP expression inhibits cell proliferation. Our study provides a novel insight that APP overexpression may contribute to the growth impairment in DS patients and promote AD pathogenesis by inhibiting cell proliferation including neural stem cell proliferation and neurogenesis. PMID:26936520

  9. Impaired theta-gamma coupling in APP-deficient mice

    PubMed Central

    Zhang, Xiaomin; Zhong, Wewei; Brankačk, Jurij; Weyer, Sascha W.; Müller, Ulrike C.; Tort, Adriano B. L.; Draguhn, Andreas

    2016-01-01

    Amyloid precursor protein (APP) is critically involved in the pathophysiology of Alzheimer’s disease, but its physiological functions remain elusive. Importantly, APP knockout (APP-KO) mice exhibit cognitive deficits, suggesting that APP plays a role at the neuronal network level. To investigate this possibility, we recorded local field potentials (LFPs) from the posterior parietal cortex, dorsal hippocampus and lateral prefrontal cortex of freely moving APP-KO mice. Spectral analyses showed that network oscillations within the theta- and gamma-frequency bands were not different between APP-KO and wild-type mice. Surprisingly, however, while gamma amplitude coupled to theta phase in all recorded regions of wild-type animals, in APP-KO mice theta-gamma coupling was strongly diminished in recordings from the parietal cortex and hippocampus, but not in LFPs recorded from the prefrontal cortex. Thus, lack of APP reduces oscillatory coupling in LFP recordings from specific brain regions, despite not affecting the amplitude of the oscillations. Together, our findings reveal reduced cross-frequency coupling as a functional marker of APP deficiency at the network level. PMID:26905287

  10. Diet and Physical Activity Apps: Perceived Effectiveness by App Users

    PubMed Central

    Egelandsdal, Bjørg; Amdam, Gro V; Almli, Valerie L; Oostindjer, Marije

    2016-01-01

    Background Diet and physical activity apps are two types of health apps that aim to promote healthy eating and energy expenditure through monitoring of dietary intake and physical activity. No clear evidence showing the effectiveness of using these apps to promote healthy eating and physical activity has been previously reported. Objective This study aimed to identify how diet and physical activity (PA) apps affected their users. It also investigated if using apps was associated with changes in diet and PA. Methods First, 3 semi-structured focus group discussions concerning app usability were conducted (15 app users and 8 nonusers; mean age 24.2 years, SD 6.4), including outcome measures such as motivations, experiences, opinions, and adherence. Results from the discussions were used to develop a questionnaire. The questionnaire, which contained questions about behavior changes, app usage, perceived effectiveness, and opinions of app usability, was answered by 500 Norwegians, with a mean age of 25.8 years (SD 5.1). Results App users found diet and PA apps effective in promoting healthy eating and exercising. These apps affected their actions, health consciousness, and self-education about nutrition and PA; and were also a part of their social lives. Over half of the users perceived that apps were effective in assisting them to eat healthily and to exercise more. Diet apps were more effective when they were frequently used and over a long period of time, compared to infrequent or short-term use (P=.01 and P=.02, respectively). Users who used diet and PA apps, perceived apps as more effective than users who only used one type of app (all P<.05). App users were better at maintaining diet and PA behaviors than nonusers (all P<.05). Young adults found apps fun to use, but sometimes time consuming. They wanted apps to be designed to meet their personal expectations. Conclusions App usage influenced action, consciousness, self-education about nutrition and PA, and social

  11. Quantifying App Store Dynamics: Longitudinal Tracking of Mental Health Apps

    PubMed Central

    Nicholas, Jennifer; Christensen, Helen

    2016-01-01

    Background For many mental health conditions, mobile health apps offer the ability to deliver information, support, and intervention outside the clinical setting. However, there are difficulties with the use of a commercial app store to distribute health care resources, including turnover of apps, irrelevance of apps, and discordance with evidence-based practice. Objective The primary aim of this study was to quantify the longevity and rate of turnover of mental health apps within the official Android and iOS app stores. The secondary aim was to quantify the proportion of apps that were clinically relevant and assess whether the longevity of these apps differed from clinically nonrelevant apps. The tertiary aim was to establish the proportion of clinically relevant apps that included claims of clinical effectiveness. We performed additional subgroup analyses using additional data from the app stores, including search result ranking, user ratings, and number of downloads. Methods We searched iTunes (iOS) and the Google Play (Android) app stores each day over a 9-month period for apps related to depression, bipolar disorder, and suicide. We performed additional app-specific searches if an app no longer appeared within the main search Results On the Android platform, 50% of the search results changed after 130 days (depression), 195 days (bipolar disorder), and 115 days (suicide). Search results were more stable on the iOS platform, with 50% of the search results remaining at the end of the study period. Approximately 75% of Android and 90% of iOS apps were still available to download at the end of the study. We identified only 35.3% (347/982) of apps as being clinically relevant for depression, of which 9 (2.6%) claimed clinical effectiveness. Only 3 included a full citation to a published study. Conclusions The mental health app environment is volatile, with a clinically relevant app for depression becoming unavailable to download every 2.9 days. This poses

  12. Clinical disease activity and acute phase reactant levels are discordant among patients with active rheumatoid arthritis: acute phase reactant levels contribute separately to predicting outcome at one year

    PubMed Central

    2014-01-01

    Introduction Clinical trials of new treatments for rheumatoid arthritis (RA) typically require subjects to have an elevated acute phase reactant (APR), in addition to tender and swollen joints. However, despite the elevation of individual components of the Clinical Disease Activity Index (CDAI) (tender and swollen joint counts and patient and physician global assessment), some patients with active RA may have normal erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels and thus fail to meet entry criteria for clinical trials. We assessed the relationship between CDAI and APRs in the Consortium of Rheumatology Researchers of North America (CORRONA) registry by comparing baseline characteristics and one-year clinical outcomes of patients with active RA, grouped by baseline APR levels. Methods This was an observational study of 9,135 RA patients who had both ESR and CRP drawn and a visit at which CDAI was >2.8 (not in remission). Results Of 9,135 patients with active RA, 58% had neither elevated ESR nor CRP; only 16% had both elevated ESR and CRP and 26% had either ESR or CRP elevated. Among the 4,228 patients who had a one-year follow-up visit, both baseline and one-year follow-up modified Health Assessment Questionnaire (mHAQ) and CDAI scores were lowest for patients with active RA but with neither APR elevated; both mHAQ and CDAI scores increased sequentially with the increase in number of elevated APR levels at baseline. Each individual component of the CDAI followed the same trend, both at baseline and at one-year follow-up. The magnitude of improvement in both CDAI and mHAQ scores at one year was associated positively with the number of APRs elevated at baseline. Conclusions In a large United States registry of RA patients, APR levels often do not correlate with disease activity as measured by joint counts and global assessments. These data strongly suggest that it is appropriate to obtain both ESR and CRP from RA patients at the initial

  13. There's an App for that!

    ERIC Educational Resources Information Center

    Dutton, Gail

    2011-01-01

    Important as training the sales force is, mobile training apps are being used for much more. Visual Eyes Inc., for example, has developed training apps for the U.S. military's combat medical teams that detail specific medical procedures, such as controlling hemorrhaging. Other apps, developed for corporations and government agencies, pass along…

  14. Smokefree Apps | Smokefree.gov

    Cancer.gov

    Get 24/7 help with a Smokefree app for your smartphone. These free apps give you the support and skills you need to get ready to quit and stay smokefree. Explore the apps to discover the features that will be most helpful for your smokefree journey.

  15. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    PubMed

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers.

  16. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    PubMed

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. PMID:26711734

  17. The pathophysiology of the acute phase of human bartonellosis resembles AIDS.

    PubMed

    Ticona, Eduardo; Huaroto, Luz; Garcia, Yuri; Vargas, Lupe; Madariaga, Miguel G

    2010-01-01

    Human bartonellosis is a South American anthroponosis caused by Bartonella bacilliformis. The disease has an acute phase characterized by invasion of red blood cells by parasites, and consequent severe anemia; and a chronic phase presenting with benign vascular tumors. During the acute phase, affected individuals are prone to developing opportunistic infections with a variety of organisms similar to the ones seen in AIDS. After antibiotic treatment is instituted, a subgroup of patients may develop atypical symptoms which potentially represent clinical manifestations of the restoration of macrophage function. We speculate that the pathophysiology of the acute phase of human bartonellosis resembles AIDS, with a period of immunosuppression following the infection and later, clinical manifestations of immune reconstitution subsequent to treatment. PMID:19665314

  18. Presence of acute phase changes in zinc, iron, and copper metabolism in turkey embryos

    SciTech Connect

    Klasing, K.C.; Richards, M.P.; Darcey, S.E.; Laurin, D.E.

    1987-01-01

    Acute phase changes in trace mineral metabolism were examined in turkey embryos. An endotoxin injection resulted in increased concentrations of serum copper and liver zinc and decreased concentrations of serum zinc in embryos incubated either in ovo or ex ovo. Changes in zinc and copper metabolism occurred when endotoxin either was injected intramuscularly, into the amnionic fluid, or administered onto the chorioallantoic membrane. Unlike poults, embryos did not respond to an inflammatory challenge with decreased serum iron concentrations. Acute phase changes in embryo serum zinc and copper as well as liver zinc concentrations were similar to those in poults. Increased liver zinc concentrations were associated with increased zinc in metallothionein (MT). An injection of a crude interleukin 1 preparation into embryos resulted in similar increases in hepatic zinc and MT concentrations as an endotoxin injection, suggesting a role for this cytokine in mediating the acute phase changes in embryonic zinc metabolism.

  19. Changes in haptoglobin, C-reactive protein and pig-MAP during a housing period following long distance transport in swine.

    PubMed

    Salamano, Germana; Mellia, Elisabetta; Candiani, Denise; Ingravalle, Francesco; Bruno, Renato; Ru, Giuseppe; Doglione, Luca

    2008-07-01

    The aim of this study was to investigate the effects of a housing period following long distance transport on haptoglobin (Hp), C-reactive protein (CRP) and pig major acute phase protein (pig-MAP) in swine. After transportation, 80 gilts were allotted to group A, B, C, or D. Blood samples were collected on arrival and 28 days later; additional samples were collected from Group C on day 14, and from Group D on days 3, 5 and 14. Acute phase proteins (APPs) in Group A were significantly lower on day 28 than on day 1; the opposite occurred in Group B because of a tail biting episode. In Group C, values remained elevated on day 14 and showed a reduction on day 28; in Group D elevated levels detected on day 14 were preceded by a decrease from days 1 to 5. The results indicate that stressors associated with transportation and new accommodation can cause an increase in APPs that could be useful indicators of welfare during transport and routine management. PMID:17509918

  20. Hemophagocytosis in the Acute Phase of Fatal Kawasaki Disease in a 4 Month-Old Girl

    PubMed Central

    Doğan, Vehbi; Karaaslan, Erhan; Özer, Samet; Gümüşer, Rüveyda; Yılmaz, Resul

    2016-01-01

    Background: Kawasaki disease is a systemic vasculitis predominately affecting coronary arteries. Hemophagocytic lymphohistiocytosis can complicate the course of Kawasaki disease. Rare cases of secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of Kawasaki disease have been reported. Case Report: We report here a 4 month-old girl with diffuse coronary ectasia and secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of incomplete Kawasaki disease. Conclusion: Due to the large overlap in clinical symptoms, the presence of atypical findings for Kawasaki disease should suggest the possible diagnosis of hemophagocytic lymphohistiocytosis in these patients. PMID:27606147

  1. Hemophagocytosis in the Acute Phase of Fatal Kawasaki Disease in a 4 Month-Old Girl

    PubMed Central

    Doğan, Vehbi; Karaaslan, Erhan; Özer, Samet; Gümüşer, Rüveyda; Yılmaz, Resul

    2016-01-01

    Background: Kawasaki disease is a systemic vasculitis predominately affecting coronary arteries. Hemophagocytic lymphohistiocytosis can complicate the course of Kawasaki disease. Rare cases of secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of Kawasaki disease have been reported. Case Report: We report here a 4 month-old girl with diffuse coronary ectasia and secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of incomplete Kawasaki disease. Conclusion: Due to the large overlap in clinical symptoms, the presence of atypical findings for Kawasaki disease should suggest the possible diagnosis of hemophagocytic lymphohistiocytosis in these patients.

  2. Caenorhabditis elegans as a model organism to study APP function

    PubMed Central

    Ewald, Collin Y.; Li, Chris

    2013-01-01

    The brains of Alzheimer's disease patients show an increased number of senile plaques compared with normal patients. The major component of the plaques is the β-amyloid peptide, a cleavage product of the amyloid precursor protein (APP). Although the processing of APP has been well-described, the physiological functions of APP and its cleavage products remain unclear. This article reviews the multifunctional roles of an APP orthologue, the C. elegans APL-1. Understanding the function of APL-1 may provide insights into the functions and signaling pathways of human APP. In addition, the physiological effects of introducing human β-amyloid peptide into C. elegans are also reviewed. The C. elegans system provides a powerful genetic model to identify genes regulating the molecular mechanisms underlying intracellular β-amyloid peptide accumulation. PMID:22038715

  3. Role of lysosomal enzymes released by alveolar macrophages in the pathogenesis of the acute phase of hypersensitivity pneumonitis

    PubMed Central

    Barrios, M. N.; Martín, T.; Sánchez, M. L.; Buitrago, J. M. González; Jiménez, A.

    1995-01-01

    Hydrolytic enzymes are the major constituents of alveolar macrophages (AM) and have been shown to be involved in many aspects of the inflammatory pulmonary response. The aim of this study was to evaluate the role of lysosomal enzymes in the acute phase of hypersensitivity pneumonitis (HPs). An experimental study on AM lysosomal enzymes of an HP-guinea-pig model was performed. The results obtained both in vivo and in vitro suggest that intracellular enzymatic activity decrease is, at least partly, due to release of lysosomal enzymes into the medium. A positive but slight correlation was found between extracellular lysosomal activity and four parameters of lung lesion (lung index, bronchoalveolar fluid total (BALF) protein concentration, BALF LDH and BALF alkaline phosphatase activities). All the above findings suggest that the AM release of lysosomal enzymes during HP is a factor involved, although possibly not the only one, in the pulmonary lesions appearing in this disease. PMID:18475615

  4. Parameters of immunity acute phase reaction in men in relation to exposure duration to mercury vapours.

    PubMed

    Moszczynski, P; Moszczynski, P; Słowinski, S; Bem, S; Bartus, R

    1991-01-01

    The study was carried out in 89 men aged 21 to 57 years with a history of exposure to mercury vapour from 2 to 26 years during occupational work involving chlorine production by the method of mercury electrolysis. The workers were divided into three groups depending on the duration of occupational exposure: 1) 32 workers with a short history of exposure 2-10 years, 2) 37 workers with medium-long exposure - 11-20 years, and 3) 20 workers with a history of long exposure - 21-26 years. The urinary concentrations of mercury in these individuals was 73 +/- 60 microliters x 1(-1), and in blood this concentration was not exceeding 50 microliters x 1(-1). The control group comprised 40 men aged 17 to 52 years. They had not had any occupational exposure to chemicals, or harmful physical factors. On the basis of clinical, haematological and biochemical studies 89 workers with occupational exposure to mercury vapour were regarded as clinically healthy. None of them had any symptoms and signs of the complete neurasthenic syndrome or organic brain injury. Increased nervous excitability was the complaint of 24 workers, 9 had headaches, sleep disturbances were reported by 5, and a feeling of tiredness and apathy was mentioned by 5 men. EEG recording demonstrated 81 normal tracings, and moderately pathological records in 8 men. The parameters of immunity and proteins acute phase reaction were determined, measuring the concentration of immunoglobulins, lysozyme, C3c, C4, alpha 1-acid glycoprotein, haptoglobin and ceruloplasmin in serum. A lower level of IgA, IgG and lysozyme was only noted in individuals with occupational exposure exceeding 20 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1725175

  5. Parameters of immunity acute phase reaction in men in relation to exposure duration to mercury vapours.

    PubMed

    Moszczynski, P; Moszczynski, P; Słowinski, S; Bem, S; Bartus, R

    1991-01-01

    The study was carried out in 89 men aged 21 to 57 years with a history of exposure to mercury vapour from 2 to 26 years during occupational work involving chlorine production by the method of mercury electrolysis. The workers were divided into three groups depending on the duration of occupational exposure: 1) 32 workers with a short history of exposure 2-10 years, 2) 37 workers with medium-long exposure - 11-20 years, and 3) 20 workers with a history of long exposure - 21-26 years. The urinary concentrations of mercury in these individuals was 73 +/- 60 microliters x 1(-1), and in blood this concentration was not exceeding 50 microliters x 1(-1). The control group comprised 40 men aged 17 to 52 years. They had not had any occupational exposure to chemicals, or harmful physical factors. On the basis of clinical, haematological and biochemical studies 89 workers with occupational exposure to mercury vapour were regarded as clinically healthy. None of them had any symptoms and signs of the complete neurasthenic syndrome or organic brain injury. Increased nervous excitability was the complaint of 24 workers, 9 had headaches, sleep disturbances were reported by 5, and a feeling of tiredness and apathy was mentioned by 5 men. EEG recording demonstrated 81 normal tracings, and moderately pathological records in 8 men. The parameters of immunity and proteins acute phase reaction were determined, measuring the concentration of immunoglobulins, lysozyme, C3c, C4, alpha 1-acid glycoprotein, haptoglobin and ceruloplasmin in serum. A lower level of IgA, IgG and lysozyme was only noted in individuals with occupational exposure exceeding 20 years.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Oyster Fisheries App

    NASA Technical Reports Server (NTRS)

    Perez Guerrero, Geraldo A.; Armstrong, Duane; Underwood, Lauren

    2015-01-01

    This project is creating a cloud-enabled, HTML 5 web application to help oyster fishermen and state agencies apply Earth science to improve the management of this important natural and economic resource. The Oyster Fisheries app gathers and analyzes environmental and water quality information, and alerts fishermen and resources managers about problems in oyster fishing waters. An intuitive interface based on Google Maps displays the geospatial information and provides familiar interactive controls to the users. Alerts can be tailored to notify users when conditions in specific leases or public fishing areas require attention. The app is hosted on the Amazon Web Services cloud. It is being developed and tested using some of the latest web development tools such as web components and Polymer.

  7. [Current treatment and management of the acute phase of Peyronies's disease].

    PubMed

    Vanni, Alex J; Bennett, Nelson E

    2009-10-01

    The true pathophysiologic nature of Peyronie's disease continues to evolve. This pathology often results in a penile plaque(s), penile deformity, curvature, pain, and erectile dysfunction. Clinically, there are two distinct phases, acute and chronic. The focus of this review will center on the management of the acute phase of Peyronie's disease. While little data exists demonstrating disease resolution, disease stabilization is an important clinical goal for patients as this often allows acceptable sexual function. Thus, medical management during the acute phase of Peyronie's disease is aimed at limiting and stabilizing the degree of penile fibrosis, decreasing penile curvature, and reducing penile pain. In this manuscript we explain different therapies; oral, topical, intralesional injection and others like extracorporeal shockwave (ESWT), radiation and penile traction for acute phase of Peyronie's disease. Although no consensus exists for the treatment of acute phase Peyronie's disease, a majority of patients can achieve stabilization and in some cases regression of their disease with proper medical therapy. The goals of therapy should be discussed extensively with each patient, noting that erectile function will be likely despite some degree of curvature.

  8. In Utero Exposure to Lipopolysaccharide Alters the Postnatal Acute Phase Response in Beef Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the potential effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to an LPS challenge in heifers. Pregnant crossbred cows (n = 50) were separated into prenatal immune stimulation (PIS; n = 25; administered 0.1 microgr...

  9. Altered postnatal acute phase response in heifers exposed to lipopolysachcharide in utero

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to LPS challenge in heifer calves. Pregnant crossbred cows (n=50) were separated into prenatal stress (PNS; n=25; administered 0.1 microgram per kilogram...

  10. Modulation of the acute phase response in feedlot steers supplemented with Saccharomyces cerevisiae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the effect of supplementing feedlot steers with Saccharomyces cerevisiae CNCM I-1079 (SC) on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 266 ± 4 kilograms body weight) were separated into three treatment groups (n = 6/treatm...

  11. Restricted feeding entrains rhythms of inflammation-related factors without promoting an acute-phase response.

    PubMed

    Luna-Moreno, Dalia; Aguilar-Roblero, Raúl; Díaz-Muñoz, Mauricio

    2009-10-01

    A restricted schedule of food access promotes numerous metabolic and physiological adaptations to optimize the biochemical handling of nutrients. The restricted feeding activates responses in hypothalamic and midbrain areas, as well as in peripheral organs involved in energy metabolism. A restricted feeding schedule (RFS) is associated with marked behavioral arousal coincident with the food anticipatory activity (FAA) and extreme hyperphagia during food access. Food restriction is also accompanied by changes in an array of stress-related parameters, such as increase in corticosterone, slower rate in body weight gain, and reduction in retroperitoneal and epididymal adipose tissue. During RFS, the liver shows a diversity of biochemical and physiologically adaptations that are advantageous for food ingestion and processing, as well as for adequate nutrient distribution to other tissues. Taking into account the probable relationship between stressful conditions and the metabolic adaptations in the liver, we addressed whether an acute-phase response (APR), or a pro-inflammatory state, occurred after three weeks of 2 h food restriction. First, we compared the circulating levels of inflammation markers (interleukin-1alpha, interleukin-6, tumor necrosis factor-alpha), and APR proteins (C-reactive protein and fibrinogen) in rats under food restriction to those in rats treated with lipopolysacharide, a strong inducer of the APR. Second, the influence of RFS on the daily rhythms of systemic cytokines and APR proteins was characterized. Third, we tested if the feeding condition (22 h fasting and 2 h refeeding) influences these parameters. Finally, we assessed if a local stressed state was established in the liver associated with the restricted feeding by measuring the activation of the transcriptional factor NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells). The results showed that the following occurred during RFS: no APR was implemented; food

  12. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study

    PubMed Central

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-01-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011–2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  13. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study.

    PubMed

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-08-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011-2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  14. Characterization of an intravenous lipopolysaccharide inflammation model in calves with respect to the acute-phase response.

    PubMed

    Plessers, Elke; Wyns, Heidi; Watteyn, Anneleen; Pardon, Bart; De Backer, Patrick; Croubels, Siska

    2015-01-15

    Our objective was to develop a lipopolysaccharide (LPS) inflammation model in calves to evaluate the acute-phase response with respect to the release of pro-inflammatory cytokines and acute-phase proteins, fever development and sickness behaviour. Fourteen 4-week-old male Holstein Friesian calves were included and randomly assigned to a negative control group (n=3) and an LPS-challenged group (n=11). The latter received an intravenous bolus injection of 0.5 μg of LPS/kg body weight. Blood collection and clinical scoring were performed at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 28, 32, 48, 54 and 72 h post LPS administration (p.a.). In the LPS group, the following clinical signs were observed successively: tachypnoea (on average 18 min p.a.), decubitus (29 min p.a.), general depression (1.75 h p.a.), fever (5h p.a.) and tachycardia (5h p.a.). Subsequent to the recovery from respiratory distress, general depression was prominent, which deteriorated when fever increased. One animal did not survive LPS administration, whereas the other animals recovered on average within 6.1h p.a. Moreover, the challenge significantly increased plasma concentrations of tumour necrosis factor-α, interleukin 6, serum amyloid A and haptoglobin, with peaking levels at 1, 3.5, 24 and 18 h p.a., respectively. The present LPS model was practical and reproducible, caused obvious clinical signs related to endotoxemia and a marked change in the studied inflammatory mediators, making it a suitable model to study the immunomodulatory properties of drugs in future research. PMID:25534079

  15. Calpain Activation in Alzheimer's Model Mice Is an Artifact of APP and Presenilin Overexpression

    PubMed Central

    Saito, Takashi; Matsuba, Yukio; Yamazaki, Naomi; Hashimoto, Shoko

    2016-01-01

    Intraneuronal calcium stimulates the calpain-dependent conversion of p35 to p25, a CDK5 activator. It is widely believed that amyloid β peptide (Aβ) induces this conversion that, in turn, has an essential role in Alzheimer's disease pathogenesis. However, in vivo studies on p25 generation used transgenic mice overexpressing mutant amyloid precursor protein (APP) and presenilin (PS). Here, using single App knock-in mice, we show that p25 generation is an artifact caused by membrane protein overexpression. We show that massive Aβ42 accumulation without overexpression of APP or presenilin does not produce p25, whereas p25 generation occurred with APP/PS overexpression and in postmortem mouse brain. We further support this finding using mice deficient for calpastatin, the sole calpain-specific inhibitor protein. Thus, the intracerebral environment of the APP/PS mouse brain and postmortem brain is an unphysiological state. SIGNIFICANCE STATEMENT We recently estimated using single App knock-in mice that accumulate amyloid β peptide without transgene overexpression that 60% of the phenotypes observed in Alzheimer's model mice overexpressing mutant amyloid precursor protein (APP) or APP and presenilin are artifacts (Saito et al., 2014). The current study further supports this estimate by invalidating key results from papers that were published in Cell. These findings suggest that more than 3000 publications based on APP and APP/PS overexpression must be reevaluated. PMID:27656030

  16. Mobile Apps for Educational Purposes.

    PubMed

    Pilcher, Jobeth

    2016-01-01

    With the growing number of mobile resources, nurse educators and professional development practitioners have the opportunity to harness mobile applications as a tool for their education toolbox. Yet, the overwhelming availability of choices can lead to questions, such as the following: How do we locate apps without spending huge amounts of our valuable time? How do we know which apps to choose? How can we evaluate apps? This article is aimed at addressing these questions. PMID:27575934

  17. Mobile Apps in Cardiology: Review

    PubMed Central

    2013-01-01

    Background Cardiovascular diseases are the deadliest diseases worldwide, with 17.3 million deaths in 2008 alone. Among them, heart-related deaths are of the utmost relevance; a fact easily proven by the 7.25 million deaths caused by ischemic heart disease alone in that year. The latest advances in smartphones and mHealth have been used in the creation of thousands of medical apps related to cardiology, which can help to reduce these mortality rates. Objective The aim of this paper is to study the literature on mobile systems and applications currently available, as well as the existing apps related to cardiology from the leading app stores and to then classify the results to see what is available and what is missing, focusing particularly on commercial apps. Methods Two reviews have been developed. One is a literature review of mobile systems and applications, retrieved from several databases and systems such as Scopus, PubMed, IEEE Xplore, and Web of Knowledge. The other is a review of mobile apps in the leading app stores, Google play for Android and Apple’s App Store for iOS. Results Search queries up to May 2013 located 406 papers and 710 apps related to cardiology and heart disease. The most researched section in the literature associated with cardiology is related to mobile heart (and vital signs) monitoring systems and the methods involved in the classification of heart signs in order to detect abnormal functions. Other systems with a significant number of papers are mobile cardiac rehabilitation systems, blood pressure measurement, and systems for the detection of heart failure. The majority of apps for cardiology are heart monitors and medical calculators. Other categories with a high number of apps are those for ECG education and interpretation, cardiology news and journals, blood pressure tracking, heart rate monitoring using an external device, and CPR instruction. There are very few guides on cardiac rehabilitation and apps for the management of the

  18. C-reactive protein

    MedlinePlus

    ... body. It is one of a group of proteins called "acute phase reactants" that go up in response to inflammation. This article discusses the blood test done to measure the amount of CRP in your blood.

  19. A Year with Google Apps

    ERIC Educational Resources Information Center

    Hastings, Robin

    2010-01-01

    In August 2008, the Missouri River Regional Library (MRRL), where the author serves as information technology coordinator, switched over from an internally hosted Microsoft Exchange email server to the Google Apps product. As the person who led the charge to use Google Apps and the person who actually flipped the switch, he was responsible for…

  20. Outstanding Symptoms of Poststroke Depression during the Acute Phase of Stroke

    PubMed Central

    Nakase, Taizen; Tobisawa, Maiko; Sasaki, Masahiro; Suzuki, Akifumi

    2016-01-01

    Poststroke depression (PSD) is a critical complication which might lead to unfavorable outcomes. However, most cases of PSD in the acute phase, during the 2 or 3 weeks following a stroke, are neglected because of the variable comorbid conditions. In this study, aimed at revealing the outstanding symptoms of PSD during the acute phase, consecutive patients with intracranial hemorrhage (ICH) or brain infarction (BI) were asked to fill out a depression questionnaire (Quick Inventory of Depressive Symptomatology Self-Report: QIDS-SR) at 1 week and 1 month following stroke onset. Patients with disturbed consciousness or aphasia were excluded from this study. Forty-nine ICH patients and 222 BI patients completed the QIDS-SR at 1 week and 27 of ICH and 62 of BI at 1 month. The PSD rate was 67% and 46% at 1 week in ICH and BI, respectively. Although sleep disturbance was the most frequent symptom of PSD, psychomotor agitation and appetite disturbance were the most distinguishing symptoms in ICH at 1 week and fatigue at 1 month. On the other hand, most of the depressive symptoms addressed in QIDS-SR were observed in PSD of BI patients both at 1 week and 1 month. In conclusion, while sleep disturbance was a frequent but non-specific symptom, appetite disturbance and fatigue might be critical symptoms to suggest PSD during the acute phase of stroke. PMID:27706193

  1. Placental thrombosis in acute phase abortions during experimental Toxoplasma gondii infection in sheep

    PubMed Central

    2014-01-01

    After oral administration of ewes during mid gestation with 2000 freshly prepared sporulated oocysts of T. gondii isolate M4, abortions occurred between days 7 and 11 in 91.6% of pregnant and infected ewes. Afterwards, a further infection was carried out at late gestation in another group of sheep with 500 sporulated oocysts. Abortions happened again between days 9 and 11 post infection (pi) in 58.3% of the infected ewes. Classically, abortions in natural and experimental ovine toxoplasmosis usually occur one month after infection. Few experimental studies have reported the so-called acute phase abortions as early as 7 to 14 days after oral inoculation of oocysts, and pyrexia was proposed to be responsible for abortion, although the underline mechanism was not elucidated. In the present study, all placentas analysed from ewes suffering acute phase abortions showed infarcts and thrombosis in the caruncullar villi of the placentomes and ischemic lesions (periventricular leukomalacia) in the brain of some foetuses. The parasite was identified by PCR in samples from some placentomes of only one sheep, and no antigen was detected by immunohistochemical labelling. These findings suggest that the vascular lesions found in the placenta, and the consequent hypoxic damage to the foetus, could be associated to the occurrence of acute phase abortions. Although the pathogenesis of these lesions remains to be determined, the infectious dose or virulence of the isolate may play a role in their development. PMID:24475786

  2. Role of TNF in sickness behavior and allodynia during the acute phase of Chagas' disease.

    PubMed

    Rodríguez-Angulo, H; Thomas, L E; Castillo, E; Cárdenas, E; Mogollón, F; Mijares, A

    2013-08-01

    Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is associated with inflammation, discomfort and pain during the acute phase. The influence of TNF-α (tumor necrosis factor) in this disease outcome is controversial. In this way, the aim of this work was to determine the role of the TNF-α blocker etanercept in the pain, discomfort, and survival during the Chagas' acute phase of mice experimentally infected with a wild virulent strain of T. cruzi. The infection with this wild strain was responsible for a severe visceral inflammation and said parasite showed a tropism in peritoneal fluid cells. Etanercept was able to restore spontaneous vertical and horizontal activities during the second week after infection and to abolish mechanical allodynia during the first week after infection. Finally, etanercept delayed the mortality without any effect on the parasitemia rates. This is the first report that correlates sickness behavior and allodynia with TNF-α and suggests that this cytokine may play an important role in the physiopathology of the acute phase. PMID:23684908

  3. Placental thrombosis in acute phase abortions during experimental Toxoplasma gondii infection in sheep.

    PubMed

    Castaño, Pablo; Fuertes, Miguel; Ferre, Ignacio; Fernández, Miguel; Ferreras, Maria del Carmen; Moreno-Gonzalo, Javier; González-Lanza, Camino; Katzer, Frank; Regidor-Cerrillo, Javier; Ortega-Mora, Luis Miguel; Pérez, Valentín; Benavides, Julio

    2014-01-29

    After oral administration of ewes during mid gestation with 2000 freshly prepared sporulated oocysts of T. gondii isolate M4, abortions occurred between days 7 and 11 in 91.6% of pregnant and infected ewes. Afterwards, a further infection was carried out at late gestation in another group of sheep with 500 sporulated oocysts. Abortions happened again between days 9 and 11 post infection (pi) in 58.3% of the infected ewes. Classically, abortions in natural and experimental ovine toxoplasmosis usually occur one month after infection. Few experimental studies have reported the so-called acute phase abortions as early as 7 to 14 days after oral inoculation of oocysts, and pyrexia was proposed to be responsible for abortion, although the underline mechanism was not elucidated. In the present study, all placentas analysed from ewes suffering acute phase abortions showed infarcts and thrombosis in the caruncullar villi of the placentomes and ischemic lesions (periventricular leukomalacia) in the brain of some foetuses. The parasite was identified by PCR in samples from some placentomes of only one sheep, and no antigen was detected by immunohistochemical labelling. These findings suggest that the vascular lesions found in the placenta, and the consequent hypoxic damage to the foetus, could be associated to the occurrence of acute phase abortions. Although the pathogenesis of these lesions remains to be determined, the infectious dose or virulence of the isolate may play a role in their development.

  4. Truncating mutations in APP cause a distinct neurological phenotype.

    PubMed

    Klein, Steven; Goldman, Alexander; Lee, Hane; Ghahremani, Shahnaz; Bhakta, Viraj; Nelson, Stanley F; Martinez-Agosto, Julian A

    2016-09-01

    Dominant missense mutations in the amyloid β (Aβ) precursor protein (APP) gene have been implicated in early onset Alzheimer disease. These mutations alter protein structure to favor the pathologic production of Aβ. We report that homozygous nonsense mutations in APP are associated with decreased somatic growth, microcephaly, hypotonia, developmental delay, thinning of the corpus callosum, and seizures. We compare the phenotype of this case to those reported in mouse models and demonstrate multiple similarities, strengthening the role of amyloid precursor protein in normal brain function and development. Ann Neurol 2016;80:456-460. PMID:27422356

  5. APP processing induced by herpes simplex virus type 1 (HSV-1) yields several APP fragments in human and rat neuronal cells.

    PubMed

    De Chiara, Giovanna; Marcocci, Maria Elena; Civitelli, Livia; Argnani, Rafaela; Piacentini, Roberto; Ripoli, Cristian; Manservigi, Roberto; Grassi, Claudio; Garaci, Enrico; Palamara, Anna Teresa

    2010-11-15

    Lifelong latent infections of the trigeminal ganglion by the neurotropic herpes simplex virus type 1 (HSV-1) are characterized by periodic reactivation. During these episodes, newly produced virions may also reach the central nervous system (CNS), causing productive but generally asymptomatic infections. Epidemiological and experimental findings suggest that HSV-1 might contribute to the pathogenesis of Alzheimer's disease (AD). This multifactorial neurodegenerative disorder is related to an overproduction of amyloid beta (Aβ) and other neurotoxic peptides, which occurs during amyloidogenic endoproteolytic processing of the transmembrane amyloid precursor protein (APP). The aim of our study was to identify the effects of productive HSV-1 infection on APP processing in neuronal cells. We found that infection of SH-SY5Y human neuroblastoma cells and rat cortical neurons is followed by multiple cleavages of APP, which result in the intra- and/or extra-cellular accumulation of various neurotoxic species. These include: i) APP fragments (APP-Fs) of 35 and 45 kDa (APP-F35 and APP-F45) that comprise portions of Aβ; ii) N-terminal APP-Fs that are secreted; iii) intracellular C-terminal APP-Fs; and iv) Aβ(1-40) and Aβ(1-42). Western blot analysis of infected-cell lysates treated with formic acid suggests that APP-F35 may be an Aβ oligomer. The multiple cleavages of APP that occur in infected cells are produced in part by known components of the amyloidogenic APP processing pathway, i.e., host-cell β-secretase, γ-secretase, and caspase-3-like enzymes. These findings demonstrate that HSV-1 infection of neuronal cells can generate multiple APP fragments with well-documented neurotoxic potentials. It is tempting to speculate that intra- and extracellular accumulation of these species in the CNS resulting from repeated HSV-1 reactivation could, in the presence of other risk factors, play a co-factorial role in the development of AD.

  6. Selecting "App"ealing and "App"ropriate Book Apps for Beginning Readers

    ERIC Educational Resources Information Center

    Cahill, Maria; McGill-Franzen, Anne

    2013-01-01

    Beginning with a brief rationale for selecting quality digital picture book apps for beginning readers, the authors describe the elements of digital picture books and provide a brief review of the instructional benefits of digital picture book use for beginning readers. They then present a detailed taxonomy for selecting quality picture book apps.…

  7. Increased exploratory activity of APP23 mice in a novel environment is reversed by siRNA.

    PubMed

    Senechal, Yann; Prut, Laetitia; Kelly, Peter H; Staufenbiel, Matthias; Natt, Francois; Hoyer, Daniel; Wiessner, Christoph; Dev, Kumlesh K

    2008-12-01

    Genetic abnormalities in amyloid precursor protein (APP) are associated with Down's syndrome and familial Alzheimer's disease where hallmark plaques contain A beta peptides derived from APP. Both APP and its derivatives are implicated in neurodegenerative processes and may play important physiological and pathophysiological roles in synaptic function. Here, we show that young APP23 transgenic mice overexpressing human APP with the Swedish double mutation display altered novelty seeking behavior before the age of plaque onset. Using short interfering RNA (siRNA) targeted against APP, we investigate the direct contribution of APP and its derivatives to this behavioral deficit. After validating siRNAs targeting human APP in vitro, siRNAs were infused directly into the brain of APP23 mice for 2 weeks. Behavioral analysis shows that infusion of siRNA targeted against APP completely reverses increased exploratory activity in APP23 mice. Collectively, these data suggest that excessive APP and/or its derivatives, causes a hyperactive phenotype in APP23 mice when placed in a novel environment, which is fully reversible and not linked to plaque deposits.

  8. Red blood cell transfusion is associated with increased hemolysis and an acute phase response in a subset of critically ill children.

    PubMed

    L'Acqua, Camilla; Bandyopadhyay, Sheila; Francis, Richard O; McMahon, Donald J; Nellis, Marianne; Sheth, Sujit; Kernie, Steven G; Brittenham, Gary M; Spitalnik, Steven L; Hod, Eldad A

    2015-10-01

    In healthy adults, transfusion of older stored red blood cells (RBCs) produces extravascular hemolysis and circulating non-transferrin-bound iron. In a prospective, observational study of critically ill children, we examined the effect of RBC storage duration on the extent of hemolysis by comparing laboratory measurements obtained before, and 4 hr after, RBC transfusion (N = 100) or saline/albumin infusion (N = 20). Transfusion of RBCs stored for longer than 4 weeks significantly increased plasma free hemoglobin (P < 0.05), indirect bilirubin (P < 0.05), serum iron (P < 0.001), and non-transferrin-bound iron (P < 0.01). However, days of storage duration poorly correlated (R(2) <0.10) with all measured indicators of hemolysis and inflammation. These results suggest that, in critically ill children, most effects of RBC storage duration on post-transfusion hemolysis are overwhelmed by recipient and/or donor factors. Nonetheless, we identified a subset of patients (N = 21) with evidence of considerable extravascular hemolysis (i.e., increased indirect bilirubin ≥0.4 mg/dL). In these patients, transfusion-associated hemolysis was accompanied by increases in circulating non-transferrin-bound iron and free hemoglobin and by an acute phase response, as assessed by an increase in median C-reactive protein levels of 21.2 mg/L (P < 0.05). In summary, RBC transfusions were associated with an acute phase response and both extravascular and intravascular hemolysis, which were independent of RBC storage duration. The 21% of transfusions that were associated with substantial hemolysis conferred an increased risk of inducing an acute phase response.

  9. The acute-phase response of cultured rat hepatocytes. System characterization and the effect of human cytokines.

    PubMed Central

    Koj, A; Gauldie, J; Regoeczi, E; Sauder, D N; Sweeney, G D

    1984-01-01

    Hepatocytes were isolated from adult livers and cultured for periods of up to 5 days as monolayers at an initial density of 10(6) cells/10cm2 in Williams E medium containing insulin, dexamethasone and 5% foetal-calf serum. The daily production of 11 plasma proteins was measured by electroimmunoassay and compared with the concentrations of the same proteins in the plasma of normal rats and of those with experimental inflammation. Hepatocytes from normal rats synthesized proteins in relative amounts which were similar to the relative proportions of the same proteins in the plasma of turpentine-injected animals. The pattern changed only slowly during 5 days in culture, but it did so profoundly either when the medium was devoid of dexamethasone or when human cytokines (from endotoxin-stimulated monocytes or unstimulated human squamous-carcinoma cell line COLO-16) were added. The cytokines consistently increased the synthesis of alpha 2-macroglobulin and fibrinogen and depressed that of albumin; variable increases in the synthesis of alpha 1-acute-phase globulin, alpha 1-acid glycoprotein, haptoglobin and alpha 1-proteinase inhibitor, and variable decreases in transferrin synthesis, were seen, whereas the synthesis of antithrombin III, alpha 1-macroglobulin and prothrombin remained virtually unaffected. The cytokine effects on protein synthesis required the presence of dexamethasone. The hepatocyte-stimulating activity derived from monocytes chromatographed on Sephadex G-100 corresponding to 30 000 Da, as opposed to the lymphocyte-activating factor, which was eluted as a molecule of approx. 15 000 Da. This suggests that both activities probably reside with distinct molecular species in the preparations of human cytokines. Images Fig. 3. PMID:6083778

  10. Creating Innovative Student Projects with App Smashing

    ERIC Educational Resources Information Center

    Young, Donna

    2014-01-01

    The potential for using various apps to improve student learning is tremendous. Yet, despite the iPad's possibilities, apps are often limited in their functionality. No one has created that magical, one-size-fits-all app that accomplishes all of the tasks that you had in mind. Luckily, there is an answer to this common problem: app smashing.…

  11. Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine.

    PubMed

    Marutle, Amelia; Ohmitsu, Masao; Nilbratt, Mats; Greig, Nigel H; Nordberg, Agneta; Sugaya, Kiminobu

    2007-07-24

    In a previous study, we found that human neural stem cells (HNSCs) exposed to high concentrations of secreted amyloid-precursor protein (sAPP) in vitro differentiated into mainly astrocytes, suggesting that pathological alterations in APP processing during neurodegenerative conditions such as Alzheimer's disease (AD) may prevent neuronal differentiation of HNSCs. Thus, successful neuroplacement therapy for AD may require regulating APP expression to favorable levels to enhance neuronal differentiation of HNSCs. Phenserine, a recently developed cholinesterase inhibitor (ChEI), has been reported to reduce APP levels in vitro and in vivo. In this study, we found reductions of APP and glial fibrillary acidic protein (GFAP) levels in the hippocampus of APP23 mice after 14 days treatment with (+)-phenserine (25 mg/kg) lacking ChEI activity. No significant change in APP gene expression was detected, suggesting that (+)-phenserine decreases APP levels and reactive astrocytes by posttranscription regulation. HNSCs transplanted into (+)-phenserine-treated APP23 mice followed by an additional 7 days of treatment with (+)-phenserine migrated and differentiated into neurons in the hippocampus and cortex after 6 weeks. Moreover, (+)-phenserine significantly increased neuronal differentiation of implanted HNSCs in hippocampal and cortical regions of APP23 mice and in the CA1 region of control mice. These results indicate that (+)-phenserine reduces APP protein in vivo and increases neuronal differentiation of HNSCs. Combination use of HNSC transplantation and treatment with drugs such as (+)-phenserine that modulate APP levels in the brain may be a useful tool for understanding mechanisms regulating stem cell migration and differentiation during neurodegenerative conditions in AD.

  12. APP Is a Context-Sensitive Regulator of the Hippocampal Presynaptic Active Zone.

    PubMed

    Laßek, Melanie; Weingarten, Jens; Wegner, Martin; Mueller, Benjamin F; Rohmer, Marion; Baeumlisberger, Dominic; Arrey, Tabiwang N; Hick, Meike; Ackermann, Jörg; Acker-Palmer, Amparo; Koch, Ina; Müller, Ulrike; Karas, Michael; Volknandt, Walter

    2016-04-01

    The hallmarks of Alzheimer's disease (AD) are characterized by cognitive decline and behavioral changes. The most prominent brain region affected by the progression of AD is the hippocampal formation. The pathogenesis involves a successive loss of hippocampal neurons accompanied by a decline in learning and memory consolidation mainly attributed to an accumulation of senile plaques. The amyloid precursor protein (APP) has been identified as precursor of Aβ-peptides, the main constituents of senile plaques. Until now, little is known about the physiological function of APP within the central nervous system. The allocation of APP to the proteome of the highly dynamic presynaptic active zone (PAZ) highlights APP as a yet unknown player in neuronal communication and signaling. In this study, we analyze the impact of APP deletion on the hippocampal PAZ proteome. The native hippocampal PAZ derived from APP mouse mutants (APP-KOs and NexCreAPP/APLP2-cDKOs) was isolated by subcellular fractionation and immunopurification. Subsequently, an isobaric labeling was performed using TMT6 for protein identification and quantification by high-resolution mass spectrometry. We combine bioinformatics tools and biochemical approaches to address the proteomics dataset and to understand the role of individual proteins. The impact of APP deletion on the hippocampal PAZ proteome was visualized by creating protein-protein interaction (PPI) networks that incorporated APP into the synaptic vesicle cycle, cytoskeletal organization, and calcium-homeostasis. The combination of subcellular fractionation, immunopurification, proteomic analysis, and bioinformatics allowed us to identify APP as structural and functional regulator in a context-sensitive manner within the hippocampal active zone network. PMID:27092780

  13. APP Is a Context-Sensitive Regulator of the Hippocampal Presynaptic Active Zone

    PubMed Central

    Mueller, Benjamin F.; Rohmer, Marion; Baeumlisberger, Dominic; Arrey, Tabiwang N.; Hick, Meike; Ackermann, Jörg; Acker-Palmer, Amparo; Koch, Ina; Müller, Ulrike; Karas, Michael; Volknandt, Walter

    2016-01-01

    The hallmarks of Alzheimer’s disease (AD) are characterized by cognitive decline and behavioral changes. The most prominent brain region affected by the progression of AD is the hippocampal formation. The pathogenesis involves a successive loss of hippocampal neurons accompanied by a decline in learning and memory consolidation mainly attributed to an accumulation of senile plaques. The amyloid precursor protein (APP) has been identified as precursor of Aβ-peptides, the main constituents of senile plaques. Until now, little is known about the physiological function of APP within the central nervous system. The allocation of APP to the proteome of the highly dynamic presynaptic active zone (PAZ) highlights APP as a yet unknown player in neuronal communication and signaling. In this study, we analyze the impact of APP deletion on the hippocampal PAZ proteome. The native hippocampal PAZ derived from APP mouse mutants (APP-KOs and NexCreAPP/APLP2-cDKOs) was isolated by subcellular fractionation and immunopurification. Subsequently, an isobaric labeling was performed using TMT6 for protein identification and quantification by high-resolution mass spectrometry. We combine bioinformatics tools and biochemical approaches to address the proteomics dataset and to understand the role of individual proteins. The impact of APP deletion on the hippocampal PAZ proteome was visualized by creating protein-protein interaction (PPI) networks that incorporated APP into the synaptic vesicle cycle, cytoskeletal organization, and calcium-homeostasis. The combination of subcellular fractionation, immunopurification, proteomic analysis, and bioinformatics allowed us to identify APP as structural and functional regulator in a context-sensitive manner within the hippocampal active zone network. PMID:27092780

  14. Keratinocytes from APP/APLP2-deficient mice are impaired in proliferation, adhesion and migration in vitro

    SciTech Connect

    Siemes, Christina; Quast, Thomas; Kummer, Christiane; Wehner, Sven; Kirfel, Gregor; Mueller, Ulrike; Herzog, Volker . E-mail: Herzog@uni-bonn.de

    2006-07-01

    Growing evidence shows that the soluble N-terminal form (sAPP{alpha}) of the amyloid precursor protein (APP) represents an epidermal growth factor fostering keratinocyte proliferation, migration and adhesion. APP is a member of a protein family including the two mammalian amyloid precursor-like proteins APLP1 and APLP2. In the mammalian epidermis, only APP and APLP2 are expressed. APP and APLP2-deficient mice die shortly after birth but do not display a specific epidermal phenotype. In this report, we investigated the epidermis of APP and/or APLP2 knockout mice. Basal keratinocytes showed reduced proliferation in vivo by about 40%. Likewise, isolated keratinocytes exhibited reduced proliferation rates in vitro, which could be completely rescued by either exogenously added recombinant sAPP{alpha}, or by co-culture with dermal fibroblasts derived from APP knockout mice. Moreover, APP-knockout keratinocytes revealed reduced migration velocity resulting from severely compromised cell substrate adhesion. Keratinocytes from double knockout mice died within the first week of culture, indicating essential functions of APP-family members for survival in vitro. Our data indicate that sAPP{alpha} has to be considered as an essential epidermal growth factor which, however, in vivo can be functionally compensated to a certain extent by other growth factors, e.g., factors released from dermal fibroblasts.

  15. APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses

    PubMed Central

    Fanutza, Tomas; Del Prete, Dolores; Ford, Michael J; Castillo, Pablo E; D’Adamio, Luciano

    2015-01-01

    The amyloid precursor protein (APP), whose mutations cause familial Alzheimer’s disease, interacts with the synaptic release machinery, suggesting a role in neurotransmission. Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain. A peptide encompassing this binding domain -named JCasp- is naturally produced by a γ-secretase/caspase double-cut of APP. JCasp interferes with the APP-presynaptic proteins interaction and, if linked to a cell-penetrating peptide, reduces glutamate release in acute hippocampal slices from wild-type but not APP deficient mice, indicating that JCasp inhibits APP function.The APP-like protein-2 (APLP2) also binds the synaptic release machinery. Deletion of APP and APLP2 produces synaptic deficits similar to those caused by JCasp. Our data support the notion that APP and APLP2 facilitate transmitter release, likely through the interaction with the neurotransmitter release machinery. Given the link of APP to Alzheimer’s disease, alterations of this synaptic role of APP could contribute to dementia. DOI: http://dx.doi.org/10.7554/eLife.09743.001 PMID:26551565

  16. APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses.

    PubMed

    Fanutza, Tomas; Del Prete, Dolores; Ford, Michael J; Castillo, Pablo E; D'Adamio, Luciano

    2015-11-09

    The amyloid precursor protein (APP), whose mutations cause familial Alzheimer's disease, interacts with the synaptic release machinery, suggesting a role in neurotransmission. Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain. A peptide encompassing this binding domain -named JCasp- is naturally produced by a γ-secretase/caspase double-cut of APP. JCasp interferes with the APP-presynaptic proteins interaction and, if linked to a cell-penetrating peptide, reduces glutamate release in acute hippocampal slices from wild-type but not APP deficient mice, indicating that JCasp inhibits APP function.The APP-like protein-2 (APLP2) also binds the synaptic release machinery. Deletion of APP and APLP2 produces synaptic deficits similar to those caused by JCasp. Our data support the notion that APP and APLP2 facilitate transmitter release, likely through the interaction with the neurotransmitter release machinery. Given the link of APP to Alzheimer's disease, alterations of this synaptic role of APP could contribute to dementia.

  17. [Aortic valve injury due to blunt trauma--treatment in acute phase].

    PubMed

    Kohno, M; Ohuchi, H; Fukuda, I

    1996-10-01

    Aortic valve injury due to blunt trauma is rare and often difficult to diagnose. Therefore, most reported cases are operated on months or years after initial injury. Reported below is the case of a 55-year-old male, who was involved in a head-on collision with a bus. He was transported to Tsukuba Medical Center by ambulance, 34 minutes after the accident. The patient presented acute shock without obvious evidence of hemorrhaging. On physical examination a murmur was detected. The murmur was evaluated by Doppler echocardiography and revealed aortic regurgitation. On further physical examination he had gross hematuria and intratracheal bleeding. Computerized tomography (CT) showed evidence of contusions to his lungs, liver, and kidneys. The individual was diagnosed with an aortic valve injury, causing aortic insufficiency. It was necessary to continuously monitor the patients' hemodynamic state, assessing when conditions to operate were most favorable. However, in the hyper-acute phase the bleeding is difficult to control. We waited for his platelet count to recover before operating on the fifth day. When the patient underwent valve repair using extracorporeal circulation (ECC), aprotinin was added to the procedure. The surgery revealed a large laceration on the right coronary cusp of the aortic valve. Repair to the valve was impossible, so replacement of the aortic valve was required. A Carbomedics mechanical valve (phi 21 mm) was inserted. The patient did well after surgery, and eventually returned to work. To date, in Japan, there are eleven such cases of aortic valve injury on file. However, this is the first reported case that involved operating during the acute phase. This case demonstrates that, with careful evaluation of coexisting injuries and control of bleeding, successful treatment of aortic valve injury using ECC is possible, even in the acute phase. PMID:8940844

  18. Value of Dynamic Susceptibility Contrast Perfusion MRI in the Acute Phase of Transient Global Amnesia

    PubMed Central

    Förster, Alex; Al-Zghloul, Mansour; Kerl, Hans U.; Böhme, Johannes; Mürle, Bettina; Groden, Christoph

    2015-01-01

    Purpose Transient global amnesia (TGA) is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI) in TGA in the acute phase. Methods From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF) and volume (CBV)) were generated and analyzed by use of Signal Processing In NMR-Software (SPIN). CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL). Results Five TGA patients were included (2 men, 3 women). On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus. Conclusions Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in

  19. Flight performance of western sandpipers, Calidris mauri, remains uncompromised when mounting an acute phase immune response.

    PubMed

    Nebel, Silke; Buehler, Deborah M; MacMillan, Alexander; Guglielmo, Christopher G

    2013-07-15

    Migratory birds have been implicated in the spread of some zoonotic diseases, but how well infected individuals can fly remains poorly understood. We used western sandpipers, Calidris mauri, to experimentally test whether flight is affected when long-distance migrants are mounting an immune response and whether migrants maintain immune defences during a flight in a wind tunnel. We measured five indicators of innate immunity in 'flown-healthy' birds (flying in a wind tunnel without mounting an immune response), 'flown-sick' birds (flying while mounting an acute phase response, which is part of induced innate immunity), and a non-flying control group ('not-flown'). Voluntary flight duration did not differ between flown-healthy and flown-sick birds, indicating that mounting an acute phase response to simulated infection did not hamper an individual's ability to fly for up to 3 h. However, in comparison to not-flown birds, bacterial killing ability of plasma was significantly reduced after flight in flown-sick birds. In flown-healthy birds, voluntary flight duration was positively correlated with bacterial killing ability and baseline haptoglobin concentration of the blood plasma measured 1-3 weeks before experimental flights, suggesting that high quality birds had strong immune systems and greater flight capacity. Our findings indicate that flight performance is not diminished by prior immune challenge, but that flight while mounting an acute phase response negatively affects other aspects of immune function. These findings have important implications for our understanding of the transmission of avian diseases, as they suggest that birds can still migrate while fighting an infection.

  20. The AppScale Cloud Platform

    PubMed Central

    Krintz, Chandra

    2013-01-01

    AppScale is an open source distributed software system that implements a cloud platform as a service (PaaS). AppScale makes cloud applications easy to deploy and scale over disparate cloud fabrics, implementing a set of APIs and architecture that also makes apps portable across the services they employ. AppScale is API-compatible with Google App Engine (GAE) and thus executes GAE applications on-premise or over other cloud infrastructures, without modification. PMID:23828721

  1. Interleukin-6 release and the acute-phase reaction in patients with acute myocardial infarction: a pilot study.

    PubMed

    Sturk, A; Hack, C E; Aarden, L A; Brouwer, M; Koster, R R; Sanders, G T

    1992-05-01

    We investigated the potential role of interleukin-6 as a mediator of the acute-phase reaction (APR) in patients with acute myocardial infarction. Of the six patients studied, five demonstrated increased plasma interleukin-6 levels. Interleukin-6 levels began to increase at 14 hours (mean; range = 8 to 20 hours) after the initial complaints and reached maximal levels of 28 to 250 U/mL (normal values less than 10 U/mL) after 36 hours (mean; range = 24 to 52 hours). No correlation was seen between the size of the interfaction as indicated by creatine kinase MB assays and the extent of the interleukin-6 increases (r = 0.44; p = 0.38). As an indicator of the APR, plasma C-reactive protein (CRP) levels were measured. CRP levels began to increase after 16 hours (mean; range = 8 to 24 hours) and reached maximum levels of 56 to 322 mg/L (normal values less than 3 mg/L) after 65 hours (mean; range = 48 to 92 hours). The increase of the interleukin-6 level preceded the increase of the CRP level in three patients and was simultaneous in two patients. Maximal interleukin-6 levels correlated significantly with maximal CRP levels (r = 0.96; p = 0.002). Thus these findings indicate that interleukin-6 is an important endogenous mediator for the APR in patients with acute myocardial infarction.

  2. Correlation of statin-increased platelet APP ratios and reduced blood lipids in AD patients.

    PubMed

    Baskin, F; Rosenberg, R N; Fang, X; Hynan, L S; Moore, C B; Weiner, M; Vega, G L

    2003-06-24

    Platelets, like neurons, contain 120- to 130- and 110-kd amyloid precursor proteins (APPs). Their ratio is reduced in AD, further reductions correlating with reduced Mini-Mental Status Examination scores [r(11) = 0.69, p < 0.05]. As statins alter APP processing, platelet APPs were analyzed in patients with AD given anticholesterol drugs for 6 weeks. APP ratios increased [t(37) = -3.888, p = 0.0004], proportionally with reduced cholesterol [r(36) = -0.45, p = 0.005]. Longer trials may reveal slowed cognitive loss, validating this index. PMID:12821755

  3. A genetic interaction between the APP and Dab1 genes influences brain development

    PubMed Central

    Pramatarova, Albéna; Chen, Kelian; Howell, Brian W.

    2008-01-01

    The Dab1 docking protein is required for the proper organization of brain laminae and for a signal transduction pathway initiated by Reelin binding to the ApoER2 and VLDLR receptors on the cell surface of neurons. Dab1 physically interacts with APP, however, it is not known whether the APP gene influences Dab1 function. Here we demonstrate a genetic interaction between Dab1 and APP. Dab1-hypomorphic animals have neuronal ectopias in the neocortex and reduced cerebellar volume, possibly a consequence of Purkinje cell misplacement. These phenotypes are exacerbated in transgenic animals overexpressing a mutant form of APP, APPswe, which is characterized by increased processing at the β-secretase site. The Dab1-hypomorphic phenotype is improved in the cerebellum of animals that are deficient for APP. Together this suggests that APP expression constrains the consequences of Dab1 activity during brain development. PMID:18029196

  4. Urologists' usage and perceptions of urological apps.

    PubMed

    Dempster, Niall J; Risk, Rachel; Clark, Ross; Meddings, Robert N

    2014-12-01

    We conducted a survey of urologists to document their patterns of app usage and perceptions of app quality, and to assess their interest in future app usage. The survey was sent to all urologists on the mailing list of the British Association of Urological Surgeons (BAUS) (n=1613). A total of 115 responses were received (a response rate of 7%). Most respondents (89%) owned mobile devices capable of downloading apps. Most respondents (79%) used apps and about half (49%) used urological apps; the latter accessed a mean of 2.4 urological apps per month. Significantly more younger (defined as <45 years old) than older urologists used urological apps (P<0.001). Respondents' perception of the overall quality of apps produced for both urologists and patients was relatively low. The respondents' interest in future app usage was strong. There was greatest interest in apps such as logbooks or revalidation ones (87%), reference apps (86%) and ones which aided decision-making (85%). There was considerable support for the implementation of measures to provide urological app quality assurance; most respondents believed app peer review (78%) and validation (78%) would be beneficial and 48% supported regulatory oversight. There appears to be a need for high quality urological apps and opportunities therefore exist for national urological associations and academic units to lead developments.

  5. DISC1 regulates trafficking and processing of APP and Aβ generation.

    PubMed

    Shahani, N; Seshadri, S; Jaaro-Peled, H; Ishizuka, K; Hirota-Tsuyada, Y; Wang, Q; Koga, M; Sedlak, T W; Korth, C; Brandon, N J; Kamiya, A; Subramaniam, S; Tomoda, T; Sawa, A

    2015-07-01

    We report the novel regulation of proteolytic processing of amyloid precursor protein (APP) by DISC1, a major risk factor for psychiatric illnesses, such as depression and schizophrenia. RNAi knockdown of DISC1 in mature primary cortical neurons led to a significant increase in the levels of intracellular α-C-terminal fragment of APP (APP-CTFα) and the corresponding N-terminal-secreted ectodomain product sAPPα. DISC1 knockdown also elicited a significant decrease in the levels of amyloid beta (Aβ)42 and Aβ40. These aberrant proteolytic events were successfully rescued by co-expression of wild-type DISC1, but not by mutant DISC1 lacking the amino acids required for the interaction with APP, suggesting that APP-DISC1 protein interactions are crucial for the regulation of the C-terminal proteolysis. In a genetically engineered model in which a major full-length DISC1 isoform is depleted, consistent changes in APP processing were seen: an increase in APP-CTFα and decrease in Aβ42 and Aβ40 levels. Finally, we found that knockdown of DISC1 increased the expression of APP at the cell surface and decreased its internalization. The presented DISC1 mechanism of APP proteolytic processing and Aβ peptide generation, which is central to Alzheimer's disease pathology, suggests a novel interface between neurological and psychiatric conditions.

  6. Membrane tethering of APP c-terminal fragments is a prerequisite for T668 phosphorylation preventing nuclear sphere generation.

    PubMed

    Bukhari, Hassan; Kolbe, Katharina; Leonhardt, Gregor; Loosse, Christina; Schröder, Elisabeth; Knauer, Shirley; Marcus, Katrin; Müller, Thorsten

    2016-11-01

    A central molecular hallmark of Alzheimer's disease (AD) is the β- and γ-secretase-mediated cleavage of the amyloid precursor protein (APP), which causes the generation of different c-terminal fragments like C99, AICD57, or AICD50 that fully or in part contain the APP transmembrane domain. In this study, we demonstrate that membrane-tethered C99 is phosphorylated by JNK3A at residue T668 (APP695 numbering) to a higher extent than AICD57, whereas AICD50 is not capable of being phosphorylated. The modification decreases the turnover of APP, while the blockade of APP cleavage increases APP phosphorylation. Generation of nuclear spheres, complexes consisting of the translocated AICD, FE65 and other proteins, is significantly reduced as soon as APP c-terminal fragments are accessible for phosphorylation. This APP modification, which we identified as significantly reduced in high plaque-load areas of the human brain, is linearly dependent on the level of APP expression. Accordingly, we show that APP abundance is likewise capable of modulating nuclear sphere generation. Thus, the precise and complex regulation of APP phosphorylation, abundance, and cleavage impacts the generation of nuclear spheres, which are under discussion of being of relevance in neurodegeneration and dementia. Future pharmacological manipulation of nuclear sphere generation may be a promising approach for AD treatment.

  7. Psych-related iPhone apps.

    PubMed

    Harrison, Anthony Mark; Goozee, Rhianna

    2014-02-01

    iPhone apps are a widely utilised technology that have recently been identified as a useful medium for health research, clinical interventions and education. While some researchers have discussed advances in app technology, others promote specific apps that are not free to access. To our knowledge, no study has conducted a review of current, free iPhone apps related to psychology, psychiatry and mental health. Therefore, we conducted a pilot, web-based review exploring free iPhone apps using a replicable search strategy within the iTunes Store search function. A selection of apps were selected and subjectively assessed in terms of their usability, utility, graphics, and associated costs for the consumer. We concluded that the apps reviewed, though novel, are limited in their scope and utility. We also note a significant gap in more scientific, evidence-based app technology, and pose some pertinent ethical questions when developing future psych-related apps.

  8. Utility of Acute Phase Proteins as Biomarkers of Transport Stress in Ewes and Beef Cattle

    PubMed Central

    Fazio, Francesco; Ferrantelli, Vincenzo; Cicero, Antonello; Piccione, Giuseppe

    2015-01-01

    The effect of transport on serum amyloid A (SAA), haptoglobin (Hp), Fibrinogen and white blood cells (WBC) was evaluated in 10 ewes and 10 beef cattle. All animals were transported by road for 6 h over a distance of about 490 km with an average speed of 80 km/h. Blood samples, collected via jugular venepuncture, were obtained before and after transport as well as after 12, 24 and 48 h rest time. One-way repeated measures analysis of variance showed a statistically significant effect of sampling time on SAA, Hp, and WBC in ewes and beef cattle. Based on these results, Hp and SAA levels, together with WBC, may be useful indicators of animal health and welfare and in predicting the risk assessment in meat inspection. PMID:27800386

  9. Utility of Acute Phase Proteins as Biomarkers of Transport Stress in Ewes and Beef Cattle

    PubMed Central

    Fazio, Francesco; Ferrantelli, Vincenzo; Cicero, Antonello; Piccione, Giuseppe

    2015-01-01

    The effect of transport on serum amyloid A (SAA), haptoglobin (Hp), Fibrinogen and white blood cells (WBC) was evaluated in 10 ewes and 10 beef cattle. All animals were transported by road for 6 h over a distance of about 490 km with an average speed of 80 km/h. Blood samples, collected via jugular venepuncture, were obtained before and after transport as well as after 12, 24 and 48 h rest time. One-way repeated measures analysis of variance showed a statistically significant effect of sampling time on SAA, Hp, and WBC in ewes and beef cattle. Based on these results, Hp and SAA levels, together with WBC, may be useful indicators of animal health and welfare and in predicting the risk assessment in meat inspection. PMID:27800365

  10. [A short-term training program reduced acute phase proteins in premenopausal women with metabolic syndrome].

    PubMed

    Rosety-Rodríguez, Manuel; Fornieles, Gabriel; Camacho-Molina, Alejandra; Rosety, Ignacio; Díaz, Antonio J; Rosety, Miguel A; Rodríguez-Pareja, Antonia; Ordonez, Francisco J

    2013-01-01

    Fundamento y objetivo: Actualmente se acepta la importancia del estatus proinflamatorio en la fisiopatología del síndrome metabólico. De hecho, ha sido propuesto como diana terapéutica en el manejo clínico de estos pacientes. Por consiguiente este estudio pretende reducir los niveles plasmáticos de reactantes de fase aguda en mujeres con síndrome metabólico mediante un corto programa de entrenamiento. Material y método: Un total de 135 mujeres jóvenes adultas (38,4 ± 3,3 años) con diagnóstico de síndrome metabólico participaron voluntariamente en este estudio. El grupo de intervención se sometió a un programa de entrenamiento aeróbico de 12 semanas, con 3 sesiones/ semana en el que duración e intensidad de la parte principal se incrementaron progresivamente. Los niveles plasmáticos de proteína C-reactiva (PCR) y fibrinógeno se determinaron mediante nefelometría y HPLC respectivamente. También se evaluaron el fitness cardiovascular mediante prueba de esfuerzo máxima e índices de distribución de masa grasa. Este protocolo fue aprobado por un Comité de Ética Institucional. Resultados: Tras completar el programa, se observo una mejora significativa del fitness cardiovascular además de una reducción también significativa de los niveles de fibrinógeno y PCR. Asimismo, se encontraron correlaciones entre niveles de reactantes e índices de distribución de masa grasa, siendo la de mayor fuerza de asociación la establecida entre PCR y perímetro cintura. Conclusión: Un programa de 12 semanas consiguió reducir los niveles de reactantes de fase aguda en mujeres con síndrome metabólico. Futuros estudios longitudinales son necesarios para conocer el impacto del efecto anti-inflamatorio del ejercicio en el manejo de estos pacientes a medio/largo plazo.

  11. The biosynthesis of acute-phase proteins in primary cultures of rat hepatocytes.

    PubMed

    Andus, T; Gross, V; Tran-Thi, T A; Schreiber, G; Nagashima, M; Heinrich, P C

    1983-07-01

    The biosynthesis and secretion of alpha 2-macroglobulin, transferrin, alpha 1-acid glycoprotein and alpha 1-proteinase inhibitor were studied in rat hepatocyte primary cultures. After labeling with [35S]methionine, two forms, which can be separated electrophoretically differing by molecular weight, were found for each of the four glycoproteins. The following molecular weights were estimated for the intracellular precursors and the secreted forms: alpha 2-macroglobulin, 176 000 and 182 000; transferrin, 84 000 and 86 000; alpha 1-acid glycoprotein, 39 000 and 43 000-60 000; alpha 1-proteinase inhibitor, 49 000 and 54 000. Carbohydrate moieties could be removed from intracellular forms by treatment with endoglucosaminidase H indicating that their oligosaccharide chains were of the high-mannose type. The extracellular forms were sensitive to sialidase. They incorporated [3H]galactose and [3H]fucose showing that their oligosaccharide chains were of the complex type. Pulse-chase experiments revealed a precursor-product relationship for the high-mannose and the complex type glycoproteins. In the hepatocyte medium newly synthesized albumin was detected after 30 min and newly synthesized glycoproteins after 60 min. Unglycosylated alpha 2-macroglobulin (162 000), transferrin (79 000), alpha 1-acid glycoprotein (23 000), and alpha 1-proteinase inhibitor (41 000) were found in the cells as well as in the medium, when the transfer of oligosaccharide chains onto the polypeptide chains was blocked by tunicamycin. Tunicamycin led to a marked reduction of the secretion of alpha 2-macroglobulin, alpha 1-acid glycoprotein and alpha 1-proteinase inhibitor, whereas the secretion of transferrin was less affected. PMID:6602705

  12. Predictors of longitudinal outcomes after unstable response to acute-phase cognitive therapy for major depressive disorder.

    PubMed

    Vittengl, Jeffrey R; Clark, Lee Anna; Thase, Michael E; Jarrett, Robin B

    2015-06-01

    After patients with major depressive disorder (MDD) respond to acute-phase cognitive therapy (CT), continuation-phase treatments may be applied to improve long-term outcomes. We clarified which CT responders experience remission, recovery, relapse, and recurrence by testing baseline demographic, clinical, and personality variables. The sample of CT responders at higher risk of relapse (N = 241) was randomized to 8 months of continuation-phase CT, double-blinded fluoxetine, or pill placebo, and followed 24 months (Jarrett & Thase, 2010). Patients with lower positive emotionality and behavioral activation at the end of acute-phase CT showed increased risk for relapse/recurrence of MDD. In addition, patients with lower positive emotionality and behavioral activation, as well as higher residual depression (including emotional, cognitive, and social facets), showed decreased probability of remission (≥6 continuous weeks of minimal or absent symptoms) after acute-phase CT. Finally, patients with greater residual depression, as well as younger age and earlier MDD onset, showed decreased probability of recovery (≥35 continuous weeks of minimal or absent symptoms) after acute-phase CT. Moderator analyses did not reveal differential prediction across the continuation phase treatment arms. These results may help clinicians gauge the prognoses and need for continuation treatment among MDD patients who respond to acute-phase CT.

  13. Thromboembolism in the Sub-Acute Phase of Spinal Cord Injury: A Systematic Review of the Literature

    PubMed Central

    Belci, Maurizio; Van Middendorp, Joost J; Al Halabi, Ahmed; Meagher, Tom M

    2016-01-01

    To review the evidence of thromboembolism incidence and prophylaxis in the sub-acute phase of spinal cord injury (SCI) 3–6 months post injury. All observational and experimental studies with any length of follow-up and no limitations on language or publication status published up to March 2015 were included. Two review authors independently selected trials for inclusion and extracted data. Outcomes studied were incidence of pulmonary embolism (PE) and deep vein thrombosis (DVT) in the sub-acute phase of SCI. The secondary outcome was type of thromboprophylaxis. Our search identified 4305 references and seven articles that met the inclusion criteria. Five papers reported PE events and three papers reported DVT events in the sub-acute phase of SCI. Studies were heterogeneous in populations, design and outcome reporting, therefore a meta-analysis was not performed. The included studies report a PE incidence of 0.5%–6.0% and DVT incidence of 2.0%–8.0% in the sub-acute phase of SCI. Thromboprophylaxis was poorly reported. Spinal patients continue to have a significant risk of PE and DVT after the acute period of their injury. Clinicians are advised to have a low threshold for suspecting venous thromboembolism in the sub-acute phase of SCI and to continue prophylactic anticoagulation therapy for a longer period of time. PMID:27790330

  14. Visualization of APP and BACE-1 approximation in neurons: new insights into the amyloidogenic pathway

    PubMed Central

    Das, Utpal; Wang, Lina; Ganguly, Archan; Saikia, Junmi M.; Wagner, Steven L.; Koo, Edward H.; Roy, Subhojit

    2016-01-01

    Cleavage of APP (amyloid precursor protein) by BACE-1 (β-site APP cleaving enzyme-1) is the rate-limiting step in amyloid-beta (Aβ) production and a neuropathologic hallmark of Alzheimer's disease (AD); thus physical approximation of this substrate-enzyme pair is a critical event with broad biological and therapeutic implications. Despite much research, neuronal locales of APP/BACE-1 convergence and APP-cleavage remain unclear. Here we report an optical assay – based on fluorescence complementation – to visualize in-cellulo APP/BACE-1 interactions as a simple on/off signal. Combined with other assays tracking the fate of internalized APP in hippocampal neurons, we found that APP/BACE-1 interact in both biosynthetic and endocytic compartments; particularly along recycling-microdomains such as dendritic spines and presynaptic boutons. In axons, APP and BACE-1 are co-transported, and also interact during transit. Finally, our assay reveals that the AD-protective “Icelandic” mutation greatly attenuates APP/BACE-1 interactions, suggesting a mechanistic basis for protection. Collectively, the data challenge canonical models and provide concrete insights into long-standing controversies in the field. PMID:26642089

  15. Visualizing APP and BACE-1 approximation in neurons yields insight into the amyloidogenic pathway.

    PubMed

    Das, Utpal; Wang, Lina; Ganguly, Archan; Saikia, Junmi M; Wagner, Steven L; Koo, Edward H; Roy, Subhojit

    2016-01-01

    Cleavage of amyloid precursor protein (APP) by BACE-1 (β-site APP cleaving enzyme-1) is the rate-limiting step in amyloid-β (Aβ) production and a neuropathologic hallmark of Alzheimer's disease; thus, physical approximation of this substrate-enzyme pair is a crucial event with broad biological and therapeutic implications. Despite much research, neuronal locales of APP and BACE-1 convergence and APP cleavage remain unclear. Here we report an optical assay, based on fluorescence complementation, for visualizing in cellulo APP-BACE-1 interactions as a simple on/off signal. Combining this with other assays tracking the fate of internalized APP in hippocampal neurons, we found that APP and BACE-1 interacted in both biosynthetic and endocytic compartments, particularly along recycling microdomains such as dendritic spines and presynaptic boutons. In axons, APP and BACE-1 were cotransported, and they also interacted during transit. Finally, our assay revealed that the Alzheimer's disease-protective 'Icelandic' mutation greatly attenuates APP-BACE-1 interactions, suggesting a mechanistic basis for protection. Collectively, the data challenge canonical models and provide concrete insights into long-standing controversies in the field. PMID:26642089

  16. 77 FR 72337 - Apps for Vehicles Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ... of Energy Efficiency and Renewable Energy Apps for Vehicles Challenge AGENCY: Office of Energy... Vehicles: improving safety and fuel efficiency through technology innovation''. DATES: See, 1. Key Challenge Dates & Deadlines in SUPPLEMENTARY INFORMATION. ADDRESSES: The Apps for Vehicles Challenge...

  17. Novel N-terminal Cleavage of APP Precludes Aβ Generation in ACAT-Defective AC29 Cells

    PubMed Central

    Huttunen, Henri J.; Puglielli, Luigi; Ellis, Blake C.; Ingano, Laura A. MacKenzie

    2009-01-01

    A common pathogenic event that occurs in all forms of Alzheimer’s disease is the progressive accumulation of amyloid β-peptide (Aβ) in brain regions responsible for higher cognitive functions. Inhibition of acyl-coenzyme A: cholesterol acyltransferase (ACAT), which generates intracellular cholesteryl esters from free cholesterol and fatty acids, reduces the biogenesis of the Aβ from the amyloid precursor protein (APP). Here we have used AC29 cells, defective in ACAT activity, to show that ACAT activity steers APP either toward or away from a novel proteolytic pathway that replaces both α and the amyloidogenic β cleavages of APP. This alternative pathway involves a novel cleavage of APP holoprotein at Glu281, which correlates with reduced ACAT activity and Aβ generation in AC29 cells. This sterol-dependent cleavage of APP occurs in the endosomal compartment after internalization of cell surface APP. The resulting novel C-terminal fragment APP-C470 is destined to proteasomal degradation limiting the availability of APP for the Aβ generating system. The proportion of APP molecules that are directed to the novel cleavage pathway is regulated by the ratio of free cholesterol and cholesteryl esters in cells. These results suggest that subcellular cholesterol distribution may be an important regulator of the cellular fate of APP holoprotein and that there may exist several competing proteolytic systems responsible for APP processing within the endosomal compartment. PMID:18618086

  18. Effect of insulin on the inflammatory and acute phase response after burn injury.

    PubMed

    Jeschke, Marc G; Boehning, Darren F; Finnerty, Celeste C; Herndon, David N

    2007-09-01

    After a severe burn, the liver plays a pivotal role by modulating inflammatory processes, metabolic pathways, immune functions, and the acute phase response. Therefore, liver integrity and function are important for recovery. A thermal injury, however, causes hepatic damage by inducing hepatic edema, fatty infiltration, hepatocyte apoptosis, and metabolic derangements associated with insulin resistance and impaired insulin signaling. In preliminary studies, we found that these pathophysiological processes are related to hepatic inflammation, altered intracellular signaling, and mitochondrial dysfunction. We hypothesize that modulation of these processes with insulin could improve hepatic structure and function and, therefore, outcome of burned and critically ill patients. Insulin administration improves survival and decreases the rate of infections in severely burned and critically ill patients. Here, we show that insulin administration decreases the synthesis of proinflammatory cytokines and signal transcription factors and improves hepatic structure and function after a severe burn injury; insulin also restores hepatic homeostasis and improves hepatic dysfunction postburn via alterations in the signaling cascade.

  19. Acupuncture as a primary and independent treatment in the acute phases of sudden sensorineural hearing loss

    PubMed Central

    Jin, Yuanyuan; Lu, Ming

    2016-01-01

    Abstract Sudden sensorineural hearing loss (SSHL) is an otological emergency defined as a rapid hearing loss, seriously affects patient's social life. To data, no study has reported the treatment by acupuncture alone in the acute phase. In this report, Acupuncture and Moxibustion therapy of excitation-focus transfer is outlined. The patient was a 26-year-old young woman who had an SSHL coupled with ear fullness. The patient had no past medical history, but she had undergone variable emotions and had a history of excessive noise exposure. The patient refused to receive any medicine especially steroids and hyperbaric oxygen therapy. She just only received acupuncture treatment. Her symptoms and outcome measurements were improved every week and completely recovered after the last week. Even though the article presents a single case and is based on self-reports, there are very clear trends on how patients with SSHL responded to acupuncture treatments. PMID:27368045

  20. Cannabis Mobile Apps: A Content Analysis

    PubMed Central

    Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

    2015-01-01

    Background Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. Objective We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. Methods The Apple and Google Play app stores were searched using the terms “cannabis” and “marijuana.” Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Results Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated “17+” years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated “high maturity” (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Conclusions Cannabis apps are generally free and highly rated. Apps were most often informational

  1. Overexpression of Swedish mutant APP in aged astrocytes attenuates excitatory synaptic transmission.

    PubMed

    Katsurabayashi, Shutaro; Kawano, Hiroyuki; Ii, Miyuki; Nakano, Sachiko; Tatsumi, Chihiro; Kubota, Kaori; Takasaki, Kotaro; Mishima, Kenichi; Fujiwara, Michihiro; Iwasaki, Katsunori

    2016-01-01

    Amyloid precursor protein (APP), a type I transmembrane protein, has different aspects, namely, performs essential physiological functions and produces β-amyloid peptide (Aβ). Overexpression of neuronal APP is responsible for synaptic dysfunction. In the central nervous system, astrocytes - a major glial cell type - have an important role in the regulation of synaptic transmission. Although APP is expressed in astrocytes, it remains unclear whether astrocytic overexpression of mutant APP affects synaptic transmission. In this study, the effect of astrocytic overexpression of a mutant APP on the excitatory synaptic transmission was investigated using coculture system of the transgenic (Tg) cortical astrocytes that express the human APP695 polypeptide with the double mutation K670N + M671L found in a large Swedish family with early onset Alzheimer's disease, and wild-type hippocampal neuron. Significant secretion of Aβ 1-40 and 1-42 was observed in cultured cortical astrocytes from the Tg2576 transgenic mouse that genetically overexpresses Swedish mutant APP. Under the condition, Tg astrocytes did not affect excitatory synaptic transmission of cocultured wild-type neurons. However, aged Tg astrocytes cultured for 9 weeks elicited a significant decrease in excitatory synaptic transmission in cocultured neurons. Moreover, a reduction in the number of readily releasable synaptic vesicles accompanied a decrease in the number of excitatory synapses in neurons cocultured with aged Tg astrocytes. These observations indicate that astrocytic expression of the mutant APP is involved in the downregulation of synaptic transmission with age. PMID:26733247

  2. Loss of presenilin function is associated with a selective gain of APP function

    PubMed Central

    Deyts, Carole; Clutter, Mary; Herrera, Stacy; Jovanovic, Natalia; Goddi, Anna; Parent, Angèle T

    2016-01-01

    Presenilin 1 (PS1) is an essential γ-secretase component, the enzyme responsible for amyloid precursor protein (APP) intramembraneous cleavage. Mutations in PS1 lead to dominant-inheritance of early-onset familial Alzheimer’s disease (FAD). Although expression of FAD-linked PS1 mutations enhances toxic Aβ production, the importance of other APP metabolites and γ-secretase substrates in the etiology of the disease has not been confirmed. We report that neurons expressing FAD-linked PS1 variants or functionally deficient PS1 exhibit enhanced axodendritic outgrowth due to increased levels of APP intracellular C-terminal fragment (APP-CTF). APP expression is required for exuberant neurite outgrowth and hippocampal axonal sprouting observed in knock-in mice expressing FAD-linked PS1 mutation. APP-CTF accumulation initiates CREB signaling cascade through an association of APP-CTF with Gαs protein. We demonstrate that pathological PS1 loss-of-function impinges on neurite formation through a selective APP gain-of-function that could impact on axodendritic connectivity and contribute to aberrant axonal sprouting observed in AD patients. DOI: http://dx.doi.org/10.7554/eLife.15645.001 PMID:27196744

  3. PAI-1 synthesis in the human hepatoma cell line HepG2 is increased by cytokines--evidence that the liver contributes to acute phase behaviour of PAI-1.

    PubMed

    de Boer, J P; Abbink, J J; Brouwer, M C; Meijer, C; Roem, D; Voorn, G P; Lambers, J W; van Mourik, J A; Hack, C E

    1991-02-12

    The acute phase behaviour of the fast inhibitor of tissue-type plasminogen activator (PAI-1) in vivo has been attributed to increased synthesis by endothelial cells. However, most other acute phase proteins in vivo are synthesized in the liver, which process is regulated by cytokines and can be studied in the hepatoma derived cell line HepG2. In this study, we investigated whether the synthesis of PAI-1 by HepG2 cells is regulated by the cytokines recombinant IL-1, rIL-6 and rTNF. Recombinant IL-1 and rTNF each increased PAI-1 synthesis by HepG2 cells two to three fold, whereas rIL-6 hardly had an effect. Mixtures of rIL-1, rIL-6 and rTNF increased PAI-1 synthesis up to eleven fold. The effects observed were not due to non-specific effects on HepG2 cell metabolism, since synthesis of alpha-2-antiplasmin was not effected by any of those cytokines, whereas fibrinogen synthesis was increased three to four fold by rIL-6, but was unaffected by rIL-1. Thus, our results demonstrate that synthesis of PAI-1 by HepG2 cells is regulated by cytokines and implicate that the acute phase behaviour of PAI-1 in vivo at least in part may be due to an increased synthesis by the liver.

  4. mHealthApps: A Repository and Database of Mobile Health Apps

    PubMed Central

    Xu, Wenlong

    2015-01-01

    Background The market of mobile health (mHealth) apps has rapidly evolved in the past decade. With more than 100,000 mHealth apps currently available, there is no centralized resource that collects information on these health-related apps for researchers in this field to effectively evaluate the strength and weakness of these apps. Objective The objective of this study was to create a centralized mHealth app repository. We expect the analysis of information in this repository to provide insights for future mHealth research developments. Methods We focused on apps from the two most established app stores, the Apple App Store and the Google Play Store. We extracted detailed information of each health-related app from these two app stores via our python crawling program, and then stored the information in both a user-friendly array format and a standard JavaScript Object Notation (JSON) format. Results We have developed a centralized resource that provides detailed information of more than 60,000 health-related apps from the Apple App Store and the Google Play Store. Using this information resource, we analyzed thousands of apps systematically and provide an overview of the trends for mHealth apps. Conclusions This unique database allows the meta-analysis of health-related apps and provides guidance for research designs of future apps in the mHealth field. PMID:25786060

  5. Illuminating Apps for Fourth Grade

    ERIC Educational Resources Information Center

    Lennex, Lesia; Bodenlos, Emily

    2014-01-01

    Elementary science is chock-full of wonderful experiences for students. Do children see iPads as a tool for learning about science? Using Prensky (2010) as a guide, the researchers decided to see if "assessing students with their own" tools (p.178) using iPad apps would support learning discrete knowledge for electricity and light…

  6. Color Addition and Subtraction Apps

    ERIC Educational Resources Information Center

    Ruiz, Frances; Ruiz, Michael J.

    2015-01-01

    Color addition and subtraction apps in HTML5 have been developed for students as an online hands-on experience so that they can more easily master principles introduced through traditional classroom demonstrations. The evolution of the additive RGB color model is traced through the early IBM color adapters so that students can proceed step by step…

  7. 15 CFR 740.7 - Computers (APP).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Computers (APP). 740.7 Section 740.7... Computers (APP). (a) Scope—(1) Commodities. License Exception APP authorizes exports and reexports of computers, including “electronic assemblies” and specially designed components therefor controlled by...

  8. 15 CFR 740.7 - Computers (APP).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Computers (APP). 740.7 Section 740.7... Computers (APP). (a) Scope—(1) Commodities. License Exception APP authorizes exports and reexports of computers, including “electronic assemblies” and specially designed components therefor controlled by...

  9. 15 CFR 740.7 - Computers (APP).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Computers (APP). 740.7 Section 740.7... Computers (APP). (a) Scope—(1) Commodities. License Exception APP authorizes exports and reexports of computers, including “electronic assemblies” and specially designed components therefor controlled by...

  10. 15 CFR 740.7 - Computers (APP).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Computers (APP). 740.7 Section 740.7... Computers (APP). (a) Scope—(1) Commodities. License Exception APP authorizes exports and reexports of computers, including “electronic assemblies” and specially designed components therefor controlled by...

  11. Capitalizing on App Development Tools and Technologies

    ERIC Educational Resources Information Center

    Luterbach, Kenneth J.; Hubbell, Kenneth R.

    2015-01-01

    Instructional developers and others creating apps must choose from a wide variety of app development tools and technologies. Some app development tools have incorporated visual programming features, which enable some drag and drop coding and contextual programming. While those features help novices begin programming with greater ease, questions…

  12. Use of smartphone apps by paediatric trainees.

    PubMed

    Jyothi, Srinivas; Halton, Fiona; Goodyear, Helen

    2015-08-01

    Over 70% of the population owns a smartphone and there are now millions of apps available. This study looks at smartphone and app use among paediatric trainees, in particular whether they are accessing medical apps to help with clinical practice. PMID:26255919

  13. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    PubMed

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability.

  14. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    PubMed

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability. PMID:26498936

  15. Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs

    PubMed Central

    Petersen, Rebecca Y.; Royse, Emily; Kemp, Matthew W.; Miura, Yuichiro; Noe, Andres; Jobe, Alan H.; Hillman, Noah H.

    2016-01-01

    Background Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP) is being increasingly used clinically to transition preterm infants at birth. Objective To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs. Methods The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF), bronchoalveolar lavage fluid (BAL), right mainstem bronchi and peripheral lung tissue were evaluated for inflammation. Results Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used. Conclusion Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep. PMID:27463520

  16. Rapid Sequential Changeover of Expressed p44 Genes during the Acute Phase of Anaplasma phagocytophilum Infection in Horses

    PubMed Central

    Wang, Xueqi; Rikihisa, Yasuko; Lai, Tzung-Hui; Kumagai, Yumi; Zhi, Ning; Reed, Stephen M.

    2004-01-01

    Anaplasma phagocytophilum immunodominant polymorphic major surface protein P44s have been hypothesized to go through antigenic variation, but the within-host dynamics of p44 expression has not been demonstrated. In the present study we investigated the composition and changes of p44 transcripts in the blood during the acute phase of well-defined laboratory A. phagocytophilum infections in naïve equine hosts. Three traveling waves of sequential population changeovers of the p44 transcript species were observed within a single peak of rickettsemia of less than 1 month. During the logarithmic increase, the rapid switch-off of the initial dominant transcript p44-18 occurred regardless of whether the bacterium was transmitted by ticks or by intravenous inoculation. Each of the subsequently dominant p44 transcript species was phylogenetically dissimilar from p44-18. Development of antibody to the hypervariable region of P44-18 during the rickettsemia suggests the suppression of dominance of immuno-cross-reactive p44 populations. When A. phagocytophilum was preincubated with plasma from the infected horse and then coincubated with HL-60 cells, the dominance of the p44-18 transcript was rapidly suppressed in vitro and most of the newly emerged p44 transcript species were previously undetected in this horse. This work provides experimental evidence of within-host p44 antigenic variation. Results suggest that the rapid and synchronized switch of expression is an intrinsic property of p44s reinitiated after transmission to naïve mammalian hosts and shaped upon exposure to immune plasma. PMID:15557606

  17. Interactions between APP secretases and inflammatory mediators

    PubMed Central

    Sastre, Magdalena; Walter, Jochen; Gentleman, Steve M

    2008-01-01

    There is now a large body of evidence linking inflammation to Alzheimer's disease (AD). This association manifests itself neuropathologically in the presence of activated microglia and astrocytes around neuritic plaques and increased levels of inflammatory mediators in the brains of AD patients. It is considered that amyloid-β peptide (Aβ), which is derived from the processing of the longer amyloid precursor protein (APP), could be the most important stimulator of this response, and therefore determining the role of the different secretases involved in its generation is essential for a better understanding of the regulation of inflammation in AD. The finding that certain non-steroidal anti-inflammatory drugs (NSAIDs) can affect the processing of APP by inhibiting β- and γ-secretases, together with recent revelations that these enzymes may be regulated by inflammation, suggest that they could be an interesting target for anti-inflammatory drugs. In this review we will discuss some of these issues and the role of the secretases in inflammation, independent of their effect on Aβ formation. PMID:18564425

  18. Are You Connected to the Best Apps?

    PubMed

    Gaudette, Robert F

    2015-11-01

    While the vast majority of pharmacists use computers to access medical information, many prefer a mobile device to find information quickly. This review discusses pharmacists' use of mobile device applications (apps) and highlights an assortment of apps that are particularly helpful. Epocrates, which provides drug information and clinical content, was the first popular smartphone app developed in this area and was used to introduce the concept. Today, apps that provide a wide range of drug information can be supplemented with apps that fine-tune specific information about drug monitoring, disease states, and cost. PMID:26629799

  19. Dried citrus pulp modulates the physiological and acute phase responses of crossbred heifers to an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding dried citrus pulp (CP) pellets on the physiological and acute phase responses (APR) of newly-received crossbred heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Heifers (n=24; 218.3±2.4 kg) were obtained from commercial sale barns and transported...

  20. Yeast cell wall supplementation alters the physiological and acute phase responses of crossbred heifers to an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to determine the effect of feeding yeast cell wall (YCW) products on the physiological and acute phase responses of crossbred newly-received heifers to an endotoxin challenge. Heifers (n = 24; 219 ± 2.4 kg) were separated into treatment groups receiving a Control diet (n = 8), ...

  1. Supplementation of Lactobacillus acidophilus fermentation product can attenuate the acute phase response following a lipopolysaccharide challenge in pigs.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if feeding a Lactobacillus acidophilus fermentation product to weaned pigs would reduce stress and acute phase responses (APR) following a lipopolysaccharide (LPS) challenge. Pigs (n=30; 6.4±0.1 kilograms body weight) were housed individually in pens with ad libi...

  2. Enhancement of the acute phase response to lipopolysaccharide in feedlot steers supplemented with OmniGen-AF

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the effect of supplementing feedlot steers with OmniGen-AF on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 270 ± 5 kilograms body weight) were separated into two treatment groups (n=9/treatment): one group was fed a standard ...

  3. OmniGen-AF supplementation modulated the physiological and acute phase responses of Brahman heifers to an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the physiological and acute phase responses (APR) of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton...

  4. The effect of feeding endophyte-infected fescue on the acute phase response to lipopolysaccharide in beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Angus heifers (n = 22; 292 ± 9.0 kg body weight) were paired by body weight and randomly placed on either an endophyte-infected (E+) or endophyte-free (E-) diet for 10 days to determine the influence of feeding endophyte-infected fescue on the physiological and acute phase responses of beef heifers ...

  5. Prenatal transportation alters the acute phase response (APR) of bull calves exposed to a lipopolysaccharide (LPS) challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if prenatal transportation influences the acute phase response (APR) to a postnatal Lipopolysaccharide (LPS) challenge. Pregnant Brahman cows (n=96) matched by age and parity were separated into transported (TRANS; n=48; transported for 2 hours on gestational day...

  6. Apps of Steel: Are Exercise Apps Providing Consumers with Realistic Expectations?: A Content Analysis of Exercise Apps for Presence of Behavior Change Theory

    ERIC Educational Resources Information Center

    Cowan, Logan T.; Van Wagenen, Sarah A.; Brown, Brittany A.; Hedin, Riley J.; Seino-Stephan, Yukiko; Hall, P. Cougar; West, Joshua H.

    2013-01-01

    Objective. To quantify the presence of health behavior theory constructs in iPhone apps targeting physical activity. Methods. This study used a content analysis of 127 apps from Apple's (App Store) "Health & Fitness" category. Coders downloaded the apps and then used an established theory-based instrument to rate each app's inclusion of…

  7. Transgenic APP expression during postnatal development causes persistent locomotor hyperactivity in the adult

    PubMed Central

    2012-01-01

    Background Transgenic mice expressing disease-associated proteins have become standard tools for studying human neurological disorders. Transgenes are often expressed using promoters chosen to drive continuous high-level expression throughout life rather than temporal and spatial fidelity to the endogenous gene. This approach has allowed us to recapitulate diseases of aging within the two-year lifespan of the laboratory mouse, but has the potential for creating aberrant phenotypes by mechanisms unrelated to the human disorder. Results We show that overexpression of the Alzheimer’s-related amyloid precursor protein (APP) during early postnatal development leads to severe locomotor hyperactivity that can be significantly attenuated by delaying transgene onset until adulthood. Our data suggest that exposure to transgenic APP during maturation influences the development of neuronal circuits controlling motor activity. Both when matched for total duration of APP overexpression and when matched for cortical amyloid burden, animals exposed to transgenic APP as juveniles are more active in locomotor assays than animals in which APP overexpression was delayed until adulthood. In contrast to motor activity, the age of APP onset had no effect on thigmotaxis in the open field as a rough measure of anxiety, suggesting that the interaction between APP overexpression and brain development is not unilateral. Conclusions Our findings indicate that locomotor hyperactivity displayed by the tet-off APP transgenic mice and several other transgenic models of Alzheimer’s disease may result from overexpression of mutant APP during postnatal brain development. Our results serve as a reminder of the potential for unexpected interactions between foreign transgenes and brain development to cause long-lasting effects on neuronal function in the adult. The tet-off APP model provides an easy means of avoiding developmental confounds by allowing transgene expression to be delayed until the

  8. Icariin Decreases the Expression of APP and BACE-1 and Reduces the β-amyloid Burden in an APP Transgenic Mouse Model of Alzheimer's Disease

    PubMed Central

    Zhang, Lan; Shen, Cong; Chu, Jin; Zhang, Ruyi; Li, Yali; Li, Lin

    2014-01-01

    Objective: The purpose of this study was to investigate the effects and pharmacological mechanisms of icariin, which is the main component in the traditional Chinese herb Epimedium, on β-amyloid (Aβ) production in an amyloid precursor protein (APP) transgenic (Tg) mouse model of Alzheimer's disease (AD). Methods: APPV717I Tg mice were randomly divided into a model group and icariin-treated (30 and 100 μmol/kg per day) groups. Learning-memory abilities were determined by Morris water maze and object recognition tests. Aβ contents were measured by enzyme-linked immunosorbent assays and immunohistochemistry. Amyloid plaques were detected by Congo red staining and Bielschowsky silver staining. The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry. Results: Ten-month-old Tg mice showed obvious learning-memory impairments, and significant increases in Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. Conclusion: Icariin reduced the Aβ burden and amyloid plaque deposition in the hippocampus of APP transgenic mice by decreasing the APP and BACE-1 levels. These novel findings suggest that icariin may be a promising treatment in patients with AD. PMID:24550686

  9. The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization

    SciTech Connect

    S Lee; Y Xue; J Hulbert; Y Wang; X Liu; B Demeler; Y Ha

    2011-12-31

    Amyloid precursor protein (APP) is genetically linked to Alzheimer's disease. APP is a type I membrane protein, and its oligomeric structure is potentially important because this property may play a role in its function or affect the processing of the precursor by the secretases to generate amyloid {beta}-peptide. Several independent studies have shown that APP can form dimers in the cell, but how it dimerizes remains controversial. At least three regions of the precursor, including a centrally located and conserved domain called E2, have been proposed to contribute to dimerization. Here we report two new crystal structures of E2, one from APP and the other from APLP1, a mammalian APP homologue. Comparison with an earlier APP structure, which was determined in a different space group, shows that the E2 domains share a conserved and antiparallel mode of dimerization. Biophysical measurements in solution show that heparin binding induces E2 dimerization. The 2.1 {angstrom} resolution electron density map also reveals phosphate ions that are bound to the protein surface. Mutational analysis shows that protein residues interacting with the phosphate ions are also involved in heparin binding. The locations of two of these residues, Arg-369 and His-433, at the dimeric interface suggest a mechanism for heparin-induced protein dimerization.

  10. Could People Get Quality Apps They Intend to Get? Taking Finding Stroke Apps for Example.

    PubMed

    Cui, Yanyan; Fu, Chen; Chang, Hong; Wu, Ying; Chang, Polun

    2016-01-01

    We conducted a study to evaluate what apps could people get and what quality these apps were when different searching keywords were used to search in different platforms. We took Stroke apps as an example with "Stroke" "Cerebrovascular Disease" and "Zhongfeng" (in Chinese) as the keywords. Two reviewers evaluated apps independently with revised MARS scale. It was interesting to see that people would get different apps from different platforms with different keywords. The results show that a good mechanism is needed to safeguard people obtain right apps from any source with any term in China. PMID:27332472

  11. Could People Get Quality Apps They Intend to Get? Taking Finding Stroke Apps for Example.

    PubMed

    Cui, Yanyan; Fu, Chen; Chang, Hong; Wu, Ying; Chang, Polun

    2016-01-01

    We conducted a study to evaluate what apps could people get and what quality these apps were when different searching keywords were used to search in different platforms. We took Stroke apps as an example with "Stroke" "Cerebrovascular Disease" and "Zhongfeng" (in Chinese) as the keywords. Two reviewers evaluated apps independently with revised MARS scale. It was interesting to see that people would get different apps from different platforms with different keywords. The results show that a good mechanism is needed to safeguard people obtain right apps from any source with any term in China.

  12. An Android Communication App Forensic Taxonomy.

    PubMed

    Azfar, Abdullah; Choo, Kim-Kwang Raymond; Liu, Lin

    2016-09-01

    Due to the popularity of Android devices and applications (apps), Android forensics is one of the most studied topics within mobile forensics. Communication apps, such as instant messaging and Voice over IP (VoIP), are one popular app category used by mobile device users, including criminals. Therefore, a taxonomy outlining artifacts of forensic interest involving the use of Android communication apps will facilitate the timely collection and analysis of evidentiary materials from such apps. In this paper, 30 popular Android communication apps were examined, where a logical extraction of the Android phone images was collected using XRY, a widely used mobile forensic tool. Various information of forensic interest, such as contact lists and chronology of messages, was recovered. Based on the findings, a two-dimensional taxonomy of the forensic artifacts of the communication apps is proposed, with the app categories in one dimension and the classes of artifacts in the other dimension. Finally, the artifacts identified in the study of the 30 communication apps are summarized using the taxonomy. It is expected that the proposed taxonomy and the forensic findings in this paper will assist forensic investigations involving Android communication apps. PMID:27443418

  13. An Android Communication App Forensic Taxonomy.

    PubMed

    Azfar, Abdullah; Choo, Kim-Kwang Raymond; Liu, Lin

    2016-09-01

    Due to the popularity of Android devices and applications (apps), Android forensics is one of the most studied topics within mobile forensics. Communication apps, such as instant messaging and Voice over IP (VoIP), are one popular app category used by mobile device users, including criminals. Therefore, a taxonomy outlining artifacts of forensic interest involving the use of Android communication apps will facilitate the timely collection and analysis of evidentiary materials from such apps. In this paper, 30 popular Android communication apps were examined, where a logical extraction of the Android phone images was collected using XRY, a widely used mobile forensic tool. Various information of forensic interest, such as contact lists and chronology of messages, was recovered. Based on the findings, a two-dimensional taxonomy of the forensic artifacts of the communication apps is proposed, with the app categories in one dimension and the classes of artifacts in the other dimension. Finally, the artifacts identified in the study of the 30 communication apps are summarized using the taxonomy. It is expected that the proposed taxonomy and the forensic findings in this paper will assist forensic investigations involving Android communication apps.

  14. Phosphorylation of the amino-terminal region of X11L regulates its interaction with APP

    PubMed Central

    Sakuma, Megumi; Tanaka, Emi; Taru, Hidenori; Tomita, Susumu; Gandy, Sam; Nairn, Angus C.; Nakaya, Tadashi; Yamamoto, Tohru; Suzuki, Toshiharu

    2013-01-01

    Summary X11-like (X11L) is neuronal adaptor protein that interacts with the amyloid β-protein precursor (APP) and regulates its metabolism. The phosphotyrosine interaction/binding (PI/PTB) domain of X11L interacts with the cytoplasmic region of APP695. We found that X11L-APP interaction is enhanced in osmotically stressed cells and X11L modification is required for the enhancement. Amino acids 221-250 (X11L221-250) are required for the enhanced association with APP in osmotically stressed cells; this motif is 118 amino acids closer to the amino-terminal end of the protein than the PI/PTB domain (amino acids 368-555). We identified two phosphorylatable seryl residues, Ser236 and Ser238, in X11L221-250 and alanyl substitution of either seryl residue diminished the enhanced association with APP. In brain Ser238 was found to be phosphorylated and phosphorylation of X11L was required for the interaction of X11L and APP. Both seryl residues in X11L221-250 are conserved in neuronal X11, but not in X11L2, a non-neuronal X11 family member that did not exhibit enhanced APP association in osmotically stressed cells. These findings indicate that the region of X11L that regulates association with APP is located outside of, and amino-terminal to, the PI/PTB domain. Modification of this regulatory region may alter the conformation of the PI/PTB domain to modulate APP binding. PMID:19222704

  15. Whole-body protein kinetics in children with kwashiorkor and infection: a comparison of egg white and milk as dietary sources of protein.

    PubMed

    Manary, M J; Brewster, D R; Broadhead, R L; Graham, S M; Hart, C A; Crowley, J R; Fjeld, C R; Yarasheski, K E

    1997-09-01

    This study tested the hypothesis that during treatment of kwashiorkor (including marasmic kwashiorkor) with infection there is a lower rate of amino acid oxidation when the dietary intake of amino acids resembles the amino acid composition of acute phase proteins (APPs). Twenty-two children in Blantyre, Malawi, with kwashiorkor and acute infection were fed an isoenergetic, isonitrogenous diet with either egg white or milk as a protein source. The whole-body amino acid oxidation rate was measured after 24 h by determining the plasma urea rate of appearance, and whole-body protein breakdown and synthesis rates were determined from the plasma leucine rate of appearance. Plasma concentrations of C-reactive protein, alpha1-antitrypsin, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) were determined on admission and at 24 and 48 h. The 11 children who received milk had a lower rate of amino acid oxidation than the children who received egg white (x +/- SD: 137 +/- 65 compared with 195 +/- 66 micromol urea x kg body wt(-1) x h(-1), P < 0.05). No significant differences were found between the two groups in the rate of whole-body protein breakdown or protein synthesis. The TNF-alpha concentration correlated inversely with whole-body protein breakdown and synthesis rates, and the IL-6 concentration correlated directly with C-reactive protein. We conclude that by making the amino acid composition of the diet resemble that of APPs in the treatment of acute kwashiorkor, the rate of amino acid oxidation can be decreased.

  16. HuD regulates coding and noncoding RNA to induce APP → Aβ processing

    PubMed Central

    Kang, Min-Ju; Abdelmohsen, Kotb; Hutchison, Emmette R.; Mitchell, Sarah J.; Grammatikakis, Ioannis; Guo, Rong; Noh, Ji Heon; Martindale, Jennifer L.; Yang, Xiaoling; Lee, Eun Kyung; Faghihi, Mohammad A.; Wahlestedt, Claes; Troncoso, Juan C.; Pletnikova, Olga; Perrone-Bizzozero, Nora; Resnick, Susan M.; de Cabo, Rafael; Mattson, Mark P.; Gorospe, Myriam

    2014-01-01

    The primarily neuronal RNA-binding protein HuD is implicated in learning and memory. Here, we report the identification of several HuD target transcripts linked to Alzheimer’s disease (AD) pathogenesis. HuD interacted with the 3’-untranslated regions (UTRs) of APP mRNA (encoding amyloid precursor protein) and BACE1 mRNA (encoding β-site APP-cleaving enzyme) and increased the half-lives of these mRNAs. HuD also associated with and stabilized the long noncoding (lnc)RNA BACE1AS, which partly complements BACE1 mRNA and enhances BACE1 expression. Consistent with HuD promoting production of APP and APP-cleaving enzyme, the levels of APP, BACE1, BACE1AS, and Aβ were higher in the brain of HuD-overexpressing mice. Importantly, cortex (superior temporal gyrus) from AD patients displayed significantly higher levels of HuD, and accordingly elevated APP, BACE1, BACE1AS, and Aβ than did cortical tissue from healthy age-matched individuals. We propose that HuD jointly promotes the production of APP and the cleavage of its amyloidogenic fragment, Aβ. PMID:24857657

  17. Effective factors on linguistic disorder during acute phase following traumatic brain injury in adults.

    PubMed

    Chabok, Shahrokh Yousefzadeh; Kapourchali, Sara Ramezani; Leili, Ehsan Kazemnezhad; Saberi, Alia; Mohtasham-Amiri, Zahra

    2012-06-01

    Traumatic brain injury (TBI) has been known to be the leading cause of breakdown and long-term disability in people under 45 years of age. This study highlights the effective factors on post-traumatic (PT) linguistic disorder and relations between linguistic and cognitive function after trauma in adults with acute TBI. A cross-sectional design was employed to study 60 post-TBI hospitalized adults aged 18-65 years. Post-traumatic (PT) linguistic disorder and cognitive deficit after TBI were respectively diagnosed using the Persian Aphasia Test (PAT) and Persian version of Mini-Mental State Examination (MMSE) at discharge. Primary post-resuscitation consciousness level was determined using the Glasgow Coma Scale (GCS). Paracilinical data was obtained by CT scan technique. Multiple logistic regression analysis illustrated that brain injury severity was the first powerful significant predictor of PT linguistic disorder after TBI and frontotemporal lesion was the second. It was also revealed that cognitive function score was significantly correlated with score of each language skill except repetition. Subsequences of TBI are more commonly language dysfunctions that demand cognitive flexibility. Moderate, severe and fronto-temporal lesion can increase the risk of processing deficit in linguistic macrostructure production and comprehension. The dissociation risk of cortical and subcortical pathways related to cognitive-linguistic processing due to intracranial lesions can augment possibility of lexical-semantic processing deficit in acute phase which probably contributes to later cognitive-communication disorder.

  18. Scintigraphic evaluation of digital circulation during the developmental and acute phases of equine laminitis

    SciTech Connect

    Trout, D.R.

    1987-01-01

    Using nuclear isotopic imaging, digital circulation was sequentially evaluated at 24-hour intervals in 11 control horses and in 9 horses affected with acute laminitis, created by administration of a high-starch ration. Following intra-arterial injection of /sup 99m/Tc macroaggregated albumin into the brachiocephalic trunk, a gamma camera and dedicated nuclear medicine computer were used to acquire static images of the right front foot. Dynamic vascular-phase and static interstitial-phase images were also obtained after jugular vein injection of /sup 99m/Tc diethylenetriamine pentaacetic acid. These procedures were performed on standing horses, using either minimal or no tranquilization. The images were quantitatively analyzed for parameters indicative of circulation to the foot as a whole and to specific regions of interest within the foot. There was no evidence of reduced total blood flow to the lamellae during either the developmental or acute phases of laminitis. Although total flow tended to increase throughout the peripheral/external regions of the foot, statistically significant elevations were consistently present only within the lamellae. Changes indicative of decreased total blood flow were noted in the central/internal regions of the foot. These alterations usually occurred coincident with or after the onset of clinical lameness.

  19. Acute phase treatment of VTE: Anticoagulation, including non-vitamin K antagonist oral anticoagulants.

    PubMed

    Hillis, Christopher M; Crowther, Mark A

    2015-06-01

    The acute phase of venous thromboembolism (VTE) treatment focuses on the prompt and safe initiation of full-dose anticoagulation to decrease morbidity and mortality. Immediate management consists of resuscitation, supportive care, and thrombolysis for patients with haemodynamically significant pulmonary embolism (PE) or limb-threatening deep-vein thrombosis (DVT). Patients with contraindications to anticoagulants are considered for vena cava filters. Disposition for the acute treatment of VTE is then considered based on published risk scores and the patient's social status, as the first seven days carries the highest risk for VTE recurrence, extension and bleeding due to anticoagulation. Next, a review of: immediate and long-term bleeding risk, comorbidities (i. e. active cancer, renal failure, obesity, thrombophilia), medications, patient preference, VTE location and potential for pregnancy should be undertaken. This will help determine the most suitable anticoagulant for immediate treatment. The non-vitamin K antagonist oral anticoagulants (NOACs), including the factor Xa inhibitors apixaban, edoxaban and rivaroxaban as well as the direct-thrombin inhibitor dabigatran, are increasing the convenience of and options available for VTE treatment. Current options for immediate treatment include low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, apixaban, or rivaroxaban. LMWH or UFH may be continued as monotherapy or transitioned to treatment with a VKA, dabigatran or edoxaban. This review describes the upfront treatment of VTE and the evolving role of NOACs in the contemporary management of VTE.

  20. Mechanisms of vascular dysfunction in acute phase of Trypanosoma cruzi infection in mice.

    PubMed

    Silva, Josiane F; Capettini, Luciano S A; da Silva, José F P; Sales-Junior, Policarpo; Cruz, Jader Santos; Cortes, Steyner F; Lemos, Virginia S

    2016-07-01

    Vascular disorders have a direct link to mortality in the acute phase of Trypanosoma cruzi infection. However, the underlying mechanisms of vascular dysfunction in this phase are largely unknown. We hypothesize that T. cruzi invades endothelial cells causing dysfunction in contractility and relaxation of the mouse aorta. Immunodetection of T. cruzi antigen TcRBP28 was observed in endothelial cells. There was a decreased endothelial nitric oxide synthase (eNOS)-derived NO-dependent vascular relaxation, and increased vascular contractility accompanied by augmented superoxide anions production. Endothelial removal, inhibition of cyclooxygenase 2 (COX-2), blockade of thromboxane A2 (TXA2) TP receptors, and scavenger of superoxide normalized the contractile response. COX-2, thromboxane synthase, inducible nitric oxide synthase (iNOS), p65 NFκB subunit and p22(phox) of NAD(P)H oxidase (NOX) subunit expressions were increased in vessels of chagasic animals. Serum TNF-α was augmented. Basal NO production, and nitrotyrosine residue expression were increased. It is concluded that T. cruzi invades mice aorta endothelial cells and increases TXA2/TP receptor/NOX-derived superoxide formation. Alongside, T. cruzi promotes systemic TNF-α increase, which stimulates iNOS expression in vessels and nitrosative stress. In light of the heart failure that develops in the chronic phase of the disease, to understand the mechanism involved in the increased contractility of the aorta is crucial.

  1. Modulation of APP Expression Reduces Aβ Deposition in a Mouse Model

    PubMed Central

    Asuni, Ayodeji A.; Guridi, Maitea; Pankiewicz, Joanna E.; Sanchez, Sandrine; Sadowski, Martin J.

    2014-01-01

    Objective Proteolytic cleavage of the amyloid precursor protein (APP) generates β-amyloid (Aβ) peptides. Prolonged accumulation of Aβ in the brain underlies the pathogenesis of Alzheimer’s disease (AD) and is regarded as a principal target for development of disease-modifying therapeutics. Methods Using CHO APP751SW cells we identified and characterized effects of 2-[(pyridine-2-ylmethyl)-amino]-phenol (2-PMAP) on APP steady-state level and Aβ production. Outcomes of 2-PMAP treatment on Aβ accumulation and associated memory deficit were studied in APPSW/PS1dE9 AD transgenic model mice. Results In CHO APP751SW cells, 2-PMAP in a dose-response manner lowered the steady-state APP level and inhibited Aβx-40 and Aβx-42 production with minimum effective concentration ≤0.5μM. The inhibitory effect of 2-PMAP on translational efficiency of APP mRNA into protein was directly confirmed using 35S-methionine/cysteine metabolic labeling technique, while APP mRNA level remained unaltered. Administration of 2-PMAP to APPSW/PS1dE9 mice reduced brain levels of full length APP and its C-terminal fragments along with lowering levels of soluble Aβx-40 and Aβx-42. Four-month chronic treatment of APPSW/PS1dE9 mice revealed no observable toxicity and improved animals’ memory performance. 2-PMAP treatment also caused significant reduction in brain Aβ deposition determined by both unbiased quantification of Aβ plaque load and biochemical analysis of formic acid extracted Aβx-40 and Aβx-42 levels and the level of oligomeric Aβ. Interpretation We demonstrate the potential of modulating APP steady-state expression level as a safe and effective approach for reducing Aβ deposition in AD transgenic model mice. PMID:24687915

  2. Redefining Cheminformatics with Intuitive Collaborative Mobile Apps

    PubMed Central

    Clark, Alex M; Ekins, Sean; Williams, Antony J

    2012-01-01

    Abstract The proliferation of mobile devices such as smartphones and tablet computers has recently been extended to include a growing ecosystem of increasingly sophisticated chemistry software packages, commonly known as apps. The capabilities that these apps can offer to the practicing chemist are approaching those of conventional desktop-based software, but apps tend to be focused on a relatively small range of tasks. To overcome this, chemistry apps must be able to seamlessly transfer data to other apps, and through the network to other devices, as well as to other platforms, such as desktops and servers, using documented file formats and protocols whenever possible. This article describes the development and state of the art with regard to chemistry-aware apps that make use of facile data interchange, and some of the scenarios in which these apps can be inserted into a chemical information workflow to increase productivity. A selection of contemporary apps is used to demonstrate their relevance to pharmaceutical research. Mobile apps represent a novel approach for delivery of cheminformatics tools to chemists and other scientists, and indications suggest that mobile devices represent a disruptive technology for drug discovery, as they have been to many other industries. PMID:23198002

  3. Paediatric Dengue Fever diagnosed through parents' epidemiologic report and preventive strategy during the acute phase of infection.

    PubMed

    Poddighe, Dimitri; Bonomelli, Irene; Giardinetti, Silvia; Nedbal, Marco; Bruni, Paola

    2016-01-01

    In Europe, Dengue Fever is one of the most frequent imported diseases and also autochthonous cases occurred in areas where the insect vector is present. Here, we describe a child returning from Philippines and diagnosed with Dengue Fever, through the information provided by parents about an ongoing outbreak in their municipality. An appropriate clinical management in the hospital was established to monitor the occurrence of complications and to cancel the risk of dengue virus transmission in the acute phase of infection.

  4. Color Addition and Subtraction Apps

    NASA Astrophysics Data System (ADS)

    Ruiz, Frances; Ruiz, Michael J.

    2015-10-01

    Color addition and subtraction apps in HTML5 have been developed for students as an online hands-on experience so that they can more easily master principles introduced through traditional classroom demonstrations. The evolution of the additive RGB color model is traced through the early IBM color adapters so that students can proceed step by step in understanding mathematical representations of RGB color. Finally, color addition and subtraction are presented for the X11 colors from web design to illustrate yet another real-life application of color mixing.

  5. A Guide to Help Consumers Choose Apps and Avoid App Overload

    ERIC Educational Resources Information Center

    Schuster, Ellen; Zimmerman, Lynda

    2014-01-01

    Mobile technology has transformed the way consumers access and use information. The exponential growth of mobile apps makes finding suitable, easy-to-use nutrition and health-related apps challenging. A guide for consumers helps them ask important questions before downloading apps. The guide can be adapted for other Extension disciplines.

  6. The Impact of Acute Phase Domain-Specific Cognitive Function on Post-stroke Functional Recovery

    PubMed Central

    Park, Jihong; Lee, Gangpyo; Lee, Shi-Uk

    2016-01-01

    Objective To assess whether the cognitive function in the acute stage evaluated by domain-specific neuropsychological assessments would be an independent predictor of functional outcome after stroke. Methods Forty patients underwent 4 domain-specific neuropsychological examinations about 3 weeks after the onset of stroke. The tests included the Boston Naming Test (BNT), the construction recall test (CRT), the construction praxis test (CPT), and the verbal fluency test (VFT). The Korean version of Modified Barthel Index (K-MBI) at 3 months and the modified Rankin Scale (mRS) at 6 months were investigated as functional outcome after stroke. Functional improvement was assessed using the change in K-MBI during the first 3 months and subjects were dichotomized into 'good status' and 'poor status' according to mRS at 6 months. The domain-specific cognitive function along with other possible predictors for functional outcome was examined using regression analysis. Results The z-score of CPT (p=0.044) and CRT (p<0.001) were independent predictors for functional improvement measured by the change in K-MBI during the first 3 months after stroke. The z-score of CPT (p=0.049) and CRT (p=0.048) were also independent predictors of functional status at post-stroke 6 months assessed by mRS. Conclusion Impairment in visuospatial construction and memory within one month after stroke can be an independent prognostic factor of functional outcome. Domain-specific neuropsychological assessments could be considered in patients with stroke in the acute phase to predict long-term functional outcome. PMID:27152270

  7. Quantifying and Qualifying the Preventive Effects of Acute-Phase Cognitive Therapy: Pathways to Personalizing Care

    PubMed Central

    Jarrett, Robin B.; Minhajuddin, Abu; Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.

    2016-01-01

    Objective To determine the extent to which prospectively identified responders to cognitive therapy (CT) for recurrent major depressive disorder (MDD) hypothesized to be lower risk show significantly less relapse/recurrence than treated higher risk counterparts across 32 months. Method Outpatients (N = 523), aged 18–70, with recurrent MDD received 12–14 weeks of CT. The last seven consecutive scores from the Hamilton Rating Scale for Depression (HRSD-17), were used to stratify/define responders (n = 290) into lower (seven HRSD-17 scores of ≤ 6; n = 49; 17%) and higher risk (n = 241; 83%). The lower risk entered the 32-month follow-up. Higher risk patients were randomized to 8 months of continuation-phase CT or clinical management plus double-blind fluoxetine or pill placebo, with a 24-month follow-up. Results Lower risk patients were significantly less likely to relapse over the first 8 months compared to higher risk (Kaplan-Meier [KM] estimates (i.e., 4.9%=lower risk; 22.1%= higher risk; log-rank χ2 = 6.83, p = .009). This increased risk was attenuated, but not completely neutralized, by active continuation-phase therapy. Over the subsequent 24 months, the lower and higher risk groups did not differ in relapse/recurrence risk. Conclusions Rapid and sustained acute-phase CT remission identifies responders who do not require continuation-phase treatment to prevent relapse (i.e., return of an index episode). To prevent recurrence (i.e., new episodes), however, strategic allocation and more frequent “dosing” of CT and/or targeted maintenance-phase treatments may be required. Longitudinal follow-up is recommended. PMID:26654211

  8. Acute-phase cytokines IL-1beta and TNF-alpha in brain development.

    PubMed

    Dziegielewska, K M; Møller, J E; Potter, A M; Ek, J; Lane, M A; Saunders, N R

    2000-03-01

    The nervous and the immune systems share several molecules that control their development and function. We studied the temporal and spatial distribution of the immunoreactivity of two acute-phase cytokines, TNF-alpha and IL-1beta, in the developing sheep neocortex and compared it with the well-described distribution of fetuin, a fetal glycoprotein also known to modulate the production of cytokines by lipopolysaccharide (LPS)-stimulated monocytes and macrophages. TNF-alpha was present first at embryonic day 30 (E30) (term is 150 days in sheep) as a faint band of immunoreactivity between the ventricular zone and the primordial plexiform layer (preplate). IL-1beta was detected at the first appearance of the cortical plate (E35-E40). Both cytokines were present on both sides of the cortical plate, which contained fetuin-positive cells, but was free from cytokine staining. By E60, TNF-alpha immunoreactivity was less prominent than that of IL-1beta and was confined to the marginal zone and outer developing white matter; IL-1beta was present in the marginal zone and in two bands of immunoreactive cells, one at the border of the cortical plate/developing layer VI (cells of neuronal morphology) and the other at the border of layer V and the developing white matter (identified as microglia). By E80, TNF-alpha staining had disappeared and IL-1beta-immunopositive microglia were no longer detectable. By E100-E140 only a few immunoreactive cells were identified in layers V-VI; these did not co-localize with fetuin-positive cells. The differences in distribution between fetuin and the two cytokines suggest that the opsonizing role of fetuin, proposed for monocyte production of cytokines, is probably not present in the developing brain. However, early in neocortical development TNF-alpha and IL-1beta were present in the subplate zone at a time of intense synaptogenesis.

  9. Nomothetic and Idiographic Symptom Change Trajectories in Acute-Phase Cognitive Therapy for Recurrent Depression

    PubMed Central

    Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.; Jarrett, Robin B.

    2013-01-01

    Objective We tested nomothetic and idiographic convergence and change in three symptom measures during acute-phase cognitive therapy (CT) for depression and compared outcomes among patients showing different change patterns. Method Outpatients (N = 362; 69% women; 85% white; age mean = 43 years) with DSM-IV recurrent major depressive disorder completed the Hamilton Rating Scale for Depression (Hamilton, 1960), Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh 1961), and Inventory for Depressive Symptomatology—Self-Report (Rush, Gullion, Basco, Jarrett, & Trivedi, 1996) on 14 occasions, and pre-/post-CT measures of social-interpersonal functioning and negative cognitive content. Results The three symptom measures marked the same severity and change constructs, and we offer improved formulas for inter-measure score conversions via their common factor. Pre-post CT symptom reductions were large (ds 1.71-1.92), and nomothetic symptom curves were log-linear (larger improvements earlier and smaller improvements later in CT). Nonetheless, only 30% of individual patients showed clear log-linear changes, whereas other patients showed linear (e.g., steady decreases; 20%), one-step (e.g., a quick drop; 16%), and unclassified (34%) patterns. Log-linear, linear, and one-step patients were generally similar to one another and superior to unclassified patients post-CT in symptom levels, response and stable remission rates, social-interpersonal functioning, and cognitive content (median d = 0.69). Conclusions Reaching a low-symptom “destination” at the end of CT via any coherent “path” is more important in the short-term than which path patients take. We discuss implications for theories of change, clinical monitoring of individuals’ progress in CT, and the need to investigate long-term outcomes of patients with differing symptom change patterns. PMID:23627652

  10. [The Ross procedure in the acute phase of infectious endocarditis in childhood].

    PubMed

    Di Filippo, S; Bozio, A; Champsaur, G; Sassolas, F; Debost, B; Perroux, V

    1999-05-01

    The Ross procedure of aortic valve replacement with a pulmonary autograft has several advantages in childhood over mechanical prostheses or homografts, especially in infectious endocarditis requiring early surgery. Between January 1997 and July 1998, 3 children with no known previous cardiac disease, aged 14 months, 10 and 11 years, had aortic valve infectious endocarditis. The causal organism was not identified in 1 case and the other two were due to staphylococcus aureus and corynebacterium diphteriae. All children had severe, rapidly progressive aortic regurgitation complicated by pulmonary oedema in the baby and systemic emboli in the two older children. Surgery was performed within 9 days, 1.5 month and 2 months after the onset of the disease. The postoperative course was uncomplicated in the 3 cases. Postoperative Doppler echocardiography showed absence of autograft dysfunction or stenosis, with the presence of pulmonary regurgitation in 1 case. Pulmonary autograft has the advantages of not requiring anticoagulation, of allowing growth of the aortic ring, of not being limited by the age of the patient and of having a low risk of degeneration and infectious endocarditis. Therefore, it seems particularly indicated for cases of complicated infectious endocarditis requiring early aortic valve replacement. The early (4.8%) and late (4.3%) mortality rates were comparable to those of other techniques and are lower than those associated with valve replacement with mechanical prostheses in cases of endocarditis (8.5% versus 40%). The secondary morbidity is 18.8% with dysfunction of the autograft and/or stenosis of the pulmonary homograft. Despite a limited follow-up, aortic valve replacement by a pulmonary homograft seems better than aortic valve replacement with a homograft or mechanical prosthesis, especially in cases of complicated infectious endocarditis requiring surgery in the acute phase. Further studies are required to confirm these encouraging results.

  11. Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity: Study Design

    PubMed Central

    2016-01-01

    Purpose Detecting sight-threatening retinopathy of prematurity (ROP) relies on a diagnostic examination (DE) performed by an experienced ophthalmologist. An alternative may be a telemedicine system where retinal images of at-risk infants are graded by readers to determine features of ROP indicating the need for a DE. Methods The multicenter “Telemedicine Approaches to Evaluating Acute-phase ROP” (e-ROP) Study is a cohort study of 2,000 infants with birth weights <1251g. At each visit, ophthalmologists perform DEs and non-physician imagers obtain iris and five retinal images with the disc positioned in the center, right, left, up anddown. Images are uploaded to a secure server for grading by non-physician readers for the detection of plus disease, stage 3 ROP and/or zone I disease, any of which indicates “referral-warranted ROP (RW-ROP).” Images from all infants with RW-ROP and a random sample of infants without RW-ROP (based on DEs) are selected for grading. Gradings are compared to DEs to determine the validity and evaluate reliability, feasibility, safety, and cost-effectiveness of the telemedicine system. Results e-ROP is conducted in 12 Clinical Centers in the US and Canada with Study Headquarters, the Data Coordinating Center and the Image Reading Center in Philadelphia and the ROP Data Center in Oklahoma City. 27 Study Center Coordinators, 34 ophthalmologists; 26 imagers, and 4 readers have been certified. All study data are submitted using a secure web-based system. Conclusion The design and findings of this study will be useful to conduct other ROP studies or evaluate telemedicine for other diseases. PMID:24955738

  12. Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury

    PubMed Central

    CHIHARA, Hideo; TAKAGI, Yasushi; NISHINO, Kazunari; YOSHIDA, Kazumichi; ARAKAWA, Yoshiki; KIKUCHI, Takayuki; TAKENOBU, Yohei; MIYAMOTO, Susumu

    2016-01-01

    To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either “with HAL suitability” or “without HAL suitability” based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL. PMID:26538291

  13. Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury.

    PubMed

    Chihara, Hideo; Takagi, Yasushi; Nishino, Kazunari; Yoshida, Kazumichi; Arakawa, Yoshiki; Kikuchi, Takayuki; Takenobu, Yohei; Miyamoto, Susumu

    2016-01-01

    To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either "with HAL suitability" or "without HAL suitability" based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL.

  14. GPR3 Stimulates Aβ Production via Interactions with APP and β-Arrestin2

    PubMed Central

    Nelson, Christopher D.; Sheng, Morgan

    2013-01-01

    The orphan G protein-coupled receptor (GPCR) GPR3 enhances the processing of Amyloid Precursor Protein (APP) to the neurotoxic beta-amyloid (Aβ) peptide via incompletely understood mechanisms. Through overexpression and shRNA knockdown experiments in HEK293 cells, we show that β-arrestin2 (βarr2), a GPCR-interacting scaffold protein reported to bind γ-secretase, is an essential factor for GPR3-stimulated Aβ production. For a panel of GPR3 receptor mutants, the degree of stimulation of Aβ production correlates with receptor-β-arrestin binding and receptor trafficking to endocytic vesicles. However, GPR3’s recruitment of βarr2 cannot be the sole explanation, because interaction with βarr2 is common to most GPCRs, whereas GPR3 is relatively unique among GPCRs in enhancing Aβ production. In addition to β-arrestin, APP is present in a complex with GPR3 and stimulation of Aβ production by GPR3 mutants correlates with their level of APP binding. Importantly, among a broader selection of GPCRs, only GPR3 and prostaglandin E receptor 2 subtype EP2 (PTGER2; another GPCR that increases Aβ production) interact with APP, and PTGER2 does so in an agonist-stimulated manner. These data indicate that a subset of GPCRs, including GPR3 and PTGER2, can associate with APP when internalized via βarr2, and thereby promote the cleavage of APP to generate Aβ. PMID:24069330

  15. Mapping the Interactions of Dengue Virus NS1 Protein with Human Liver Proteins Using a Yeast Two-Hybrid System: Identification of C1q as an Interacting Partner

    PubMed Central

    Allonso, Diego; Nogueira, Mauricio L.; Mohana-Borges, Ronaldo

    2013-01-01

    Dengue constitutes a global health concern. The clinical manifestation of this disease varies from mild febrile illness to severe hemorrhage and/or fatal hypovolemic shock. Flavivirus nonstructural protein 1 (NS1) is a secreted glycoprotein that is displayed on the surface of infected cells but is absent in viral particles. NS1 accumulates at high levels in the plasma of dengue virus (DENV)-infected patients, and previous reports highlight its involvement in immune evasion, dengue severity, liver dysfunction and pathogenesis. In the present study, we performed a yeast two-hybrid screen to search for DENV2 NS1-interacting partners using a human liver cDNA library. We identified fifty genes, including human complement component 1 (C1q), which was confirmed by coimmunoprecipitation, ELISA and immunofluorescence assays, revealing for the first time the direct binding of this protein to NS1. Furthermore, the majority of the identified genes encode proteins that are secreted into the plasma of patients, and most of these proteins are classified as acute-phase proteins (APPs), such as plasminogen, haptoglobin, hemopexin, α-2-HS-glycoprotein, retinol binding protein 4, transferrin, and C4. The results presented here confirm the direct interaction of DENV NS1 with a key protein of the complement system and suggest a role for this complement protein in the pathogenesis of DENV infection. PMID:23516407

  16. App Usage Factor: A Simple Metric to Compare the Population Impact of Mobile Medical Apps

    PubMed Central

    Wyatt, Jeremy C

    2015-01-01

    Background One factor when assessing the quality of mobile apps is quantifying the impact of a given app on a population. There is currently no metric which can be used to compare the population impact of a mobile app across different health care disciplines. Objective The objective of this study is to create a novel metric to characterize the impact of a mobile app on a population. Methods We developed the simple novel metric, app usage factor (AUF), defined as the logarithm of the product of the number of active users of a mobile app with the median number of daily uses of the app. The behavior of this metric was modeled using simulated modeling in Python, a general-purpose programming language. Three simulations were conducted to explore the temporal and numerical stability of our metric and a simulated app ecosystem model using a simulated dataset of 20,000 apps. Results Simulations confirmed the metric was stable between predicted usage limits and remained stable at extremes of these limits. Analysis of a simulated dataset of 20,000 apps calculated an average value for the app usage factor of 4.90 (SD 0.78). A temporal simulation showed that the metric remained stable over time and suitable limits for its use were identified. Conclusions A key component when assessing app risk and potential harm is understanding the potential population impact of each mobile app. Our metric has many potential uses for a wide range of stakeholders in the app ecosystem, including users, regulators, developers, and health care professionals. Furthermore, this metric forms part of the overall estimate of risk and potential for harm or benefit posed by a mobile medical app. We identify the merits and limitations of this metric, as well as potential avenues for future validation and research. PMID:26290093

  17. Expert Involvement Predicts mHealth App Downloads: Multivariate Regression Analysis of Urology Apps

    PubMed Central

    Osório, Luís; Cavadas, Vitor; Fraga, Avelino; Carrasquinho, Eduardo; Cardoso de Oliveira, Eduardo; Castelo-Branco, Miguel; Roobol, Monique J

    2016-01-01

    Background Urological mobile medical (mHealth) apps are gaining popularity with both clinicians and patients. mHealth is a rapidly evolving and heterogeneous field, with some urology apps being downloaded over 10,000 times and others not at all. The factors that contribute to medical app downloads have yet to be identified, including the hypothetical influence of expert involvement in app development. Objective The objective of our study was to identify predictors of the number of urology app downloads. Methods We reviewed urology apps available in the Google Play Store and collected publicly available data. Multivariate ordinal logistic regression evaluated the effect of publicly available app variables on the number of apps being downloaded. Results Of 129 urology apps eligible for study, only 2 (1.6%) had >10,000 downloads, with half having ≤100 downloads and 4 (3.1%) having none at all. Apps developed with expert urologist involvement (P=.003), optional in-app purchases (P=.01), higher user rating (P<.001), and more user reviews (P<.001) were more likely to be installed. App cost was inversely related to the number of downloads (P<.001). Only data from the Google Play Store and the developers’ websites, but not other platforms, were publicly available for analysis, and the level and nature of expert involvement was not documented. Conclusions The explicit participation of urologists in app development is likely to enhance its chances to have a higher number of downloads. This finding should help in the design of better apps and further promote urologist involvement in mHealth. Official certification processes are required to ensure app quality and user safety. PMID:27421338

  18. Intraneuronal APP and extracellular Aβ independently cause dendritic spine pathology in transgenic mouse models of Alzheimer's disease.

    PubMed

    Zou, Chengyu; Montagna, Elena; Shi, Yuan; Peters, Finn; Blazquez-Llorca, Lidia; Shi, Song; Filser, Severin; Dorostkar, Mario M; Herms, Jochen

    2015-06-01

    Alzheimer's disease (AD) is thought to be caused by accumulation of amyloid-β protein (Aβ), which is a cleavage product of amyloid precursor protein (APP). Transgenic mice overexpressing APP have been used to recapitulate amyloid-β pathology. Among them, APP23 and APPswe/PS1deltaE9 (deltaE9) mice are extensively studied. APP23 mice express APP with Swedish mutation and develop amyloid plaques late in their life, while cognitive deficits are observed in young age. In contrast, deltaE9 mice with mutant APP and mutant presenilin-1 develop amyloid plaques early but show typical cognitive deficits in old age. To unveil the reasons for different progressions of cognitive decline in these commonly used mouse models, we analyzed the number and turnover of dendritic spines as important structural correlates for learning and memory. Chronic in vivo two-photon imaging in apical tufts of layer V pyramidal neurons revealed a decreased spine density in 4-5-month-old APP23 mice. In age-matched deltaE9 mice, in contrast, spine loss was only observed on cortical dendrites that were in close proximity to amyloid plaques. In both cases, the reduced spine density was caused by decreased spine formation. Interestingly, the patterns of alterations in spine morphology differed between these two transgenic mouse models. Moreover, in APP23 mice, APP was found to accumulate intracellularly and its content was inversely correlated with the absolute spine density and the relative number of mushroom spines. Collectively, our results suggest that different pathological mechanisms, namely an intracellular accumulation of APP or extracellular amyloid plaques, may lead to spine abnormalities in young adult APP23 and deltaE9 mice, respectively. These distinct features, which may represent very different mechanisms of synaptic failure in AD, have to be taken into consideration when translating results from animal studies to the human disease. PMID:25862638

  19. Will HTML5 Kill the Native App?

    ERIC Educational Resources Information Center

    Fredette, Michelle

    2013-01-01

    For colleges and universities today, the question is no longer whether to develop a campus app or not. Instead, the debate has shifted to the best--and most cost-efficient--way to make campus applications accessible to the myriad devices and operating systems out there. Schools have a few options: They can develop multiple native app versions;…

  20. Many Smartphone 'Fertility Apps' May Not Work

    MedlinePlus

    ... awareness apps found most don't use accurate methods that are based on scientific evidence. Also, many have a disclaimer saying they shouldn't be used to prevent pregnancy, Duane's study found. The ... use evidence-based methods. Each of the remaining 40 apps was assessed ...

  1. Cool Apps: Productivity at Your Fingertips

    ERIC Educational Resources Information Center

    Flaherty, Bill

    2013-01-01

    In addition to listing apps and their value, this article focuses on ways people can be more productive by adopting certain workflows in several ways. Apps listed herein include those useful in calendaring, printing, photo-editing, image-recognition, image scanning, electronic signatures, and making and sharing lists and notes.

  2. App Development Paradigms for Instructional Developers

    ERIC Educational Resources Information Center

    Luterbach, Kenneth J.; Hubbell, Kenneth R.

    2015-01-01

    To create instructional apps for desktop, laptop and mobile devices, developers must select a development tool. Tool selection is critical and complicated by the large number and variety of app development tools. One important criterion to consider is the type of development environment, which may primarily be visual or symbolic. Those distinct…

  3. Is There an App for that?

    ERIC Educational Resources Information Center

    Douglas, Karen H.; Wojcik, Brian W.; Thompson, James R.

    2012-01-01

    Everyday technologies (e.g., iPods, iPads, and Smart Phones) other applications (apps) that can serve as supports to students with intellectual and related developmental disabilities. The extent to which apps that are currently on the market are aligned with the support needs of children was evaluated using the subscale framework of the…

  4. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    SciTech Connect

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja; Szarek, Józef; Wu, Dongmei; Williams, Andrew; Andersen, Ole; Jacobsen, Nicklas R.; Yauk, Carole L.; Wallin, Håkan; Halappanavar, Sabina; Vogel, Ulla

    2015-03-15

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of small, entangled (CNT{sub Small}, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNT{sub Large}, 4 ± 0.4 μm long). Liver tissues and plasma were harvested 1, 3 and 28 days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNT{sub Large} exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease. - Highlights: • Systemic and hepatic alterations were evaluated in female mice following MWCNT instillation. • Despite being physicochemically

  5. Cell biology apps for Apple devices.

    PubMed

    Stark, Louisa A

    2012-01-01

    Apps for touch-pad devices hold promise for guiding and supporting learning. Students may use them in the classroom or on their own for didactic instruction, just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and iPhone) have a substantial share of the touch-pad device market (Campbell, 2012), this Feature will explore cell biology apps available from the App Store. My review includes iPad and iPhone apps available in June 2012, but does not include courses, lectures, podcasts, audiobooks, texts, or other books. I rated each app on a five-point scale (1 star = lowest; 5 stars = highest) for educational and production values; I also provide an overall score.

  6. Cell biology apps for Apple devices.

    PubMed

    Stark, Louisa A

    2012-01-01

    Apps for touch-pad devices hold promise for guiding and supporting learning. Students may use them in the classroom or on their own for didactic instruction, just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and iPhone) have a substantial share of the touch-pad device market (Campbell, 2012), this Feature will explore cell biology apps available from the App Store. My review includes iPad and iPhone apps available in June 2012, but does not include courses, lectures, podcasts, audiobooks, texts, or other books. I rated each app on a five-point scale (1 star = lowest; 5 stars = highest) for educational and production values; I also provide an overall score. PMID:22949420

  7. Smart apps for the smart plastic surgeon

    PubMed Central

    Venkataram, Aniketh; Ellur, Sunderraj; Kujur, Abha Rani; Joseph, Vijay

    2015-01-01

    Smartphones have the ability to benefit plastic surgeons in all aspects of patient care and education. With the sheer number of applications available and more being created everyday, it is easy to miss out on apps which could be of great relevance. Moreover, the range of android applications available has not been extensively discussed in the literature. To this end, we have compiled an exhaustive list of android smartphone applications, which we feel can help our day to day functioning. The apps have been extensively reviewed and neatly described along with all their potential uses. In addition, we have made an effort to highlight ‘non-medical’ or efficiency apps which can improve departmental functioning. These apps have not been described in prior articles, and their functionality might not be known to all. We believe that the technology savvy plastic surgeon can make maximum use of these apps to his benefit. PMID:25991890

  8. Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice.

    PubMed

    Tian, Tian; Bai, Dong; Li, Wen; Huang, Guo-Wei; Liu, Huan

    2016-09-09

    Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase. Herein, we demonstrated that folic acid reduced the deposition of Aβ42 in APP/PS1 mice brain by decreasing the mRNA and protein expressions of β-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and γ-secretase complex catalytic component-presenilin 1 (PS1)-in APP/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important α-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of γ-secretase complex. Moreover, folic acid regulated the expression of miR-126-3p and miR-339-5p, which target ADAM9 and BACE1, respectively. Taken together, the effect of folic acid on Aβ deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing β-secretase and increasing α-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression.

  9. Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice.

    PubMed

    Tian, Tian; Bai, Dong; Li, Wen; Huang, Guo-Wei; Liu, Huan

    2016-01-01

    Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase. Herein, we demonstrated that folic acid reduced the deposition of Aβ42 in APP/PS1 mice brain by decreasing the mRNA and protein expressions of β-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and γ-secretase complex catalytic component-presenilin 1 (PS1)-in APP/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important α-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of γ-secretase complex. Moreover, folic acid regulated the expression of miR-126-3p and miR-339-5p, which target ADAM9 and BACE1, respectively. Taken together, the effect of folic acid on Aβ deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing β-secretase and increasing α-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression. PMID:27618097

  10. Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

    PubMed Central

    Tian, Tian; Bai, Dong; Li, Wen; Huang, Guo-Wei; Liu, Huan

    2016-01-01

    Alzheimer’s disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase. Herein, we demonstrated that folic acid reduced the deposition of Aβ42 in APP/PS1 mice brain by decreasing the mRNA and protein expressions of β-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and γ-secretase complex catalytic component—presenilin 1 (PS1)—in APP/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important α-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of γ-secretase complex. Moreover, folic acid regulated the expression of miR-126-3p and miR-339-5p, which target ADAM9 and BACE1, respectively. Taken together, the effect of folic acid on Aβ deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing β-secretase and increasing α-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression. PMID:27618097

  11. Cholesterol accumulation in Niemann Pick type C (NPC) model cells causes a shift in APP localization to lipid rafts

    SciTech Connect

    Kosicek, Marko; Malnar, Martina; Goate, Alison; Hecimovic, Silva

    2010-03-12

    It has been suggested that cholesterol may modulate amyloid-{beta} (A{beta}) formation, a causative factor of Alzheimer's disease (AD), by regulating distribution of the three key proteins in the pathogenesis of AD ({beta}-amyloid precursor protein (APP), {beta}-secretase (BACE1) and/or presenilin 1 (PS1)) within lipid rafts. In this work we tested whether cholesterol accumulation upon NPC1 dysfunction, which causes Niemann Pick type C disease (NPC), causes increased partitioning of APP into lipid rafts leading to increased CTF/A{beta} formation in these cholesterol-rich membrane microdomains. To test this we used CHO NPC1{sup -/-} cells (NPC cells) and parental CHOwt cells. By sucrose density gradient centrifugation we observed a shift in fl-APP/CTF compartmentalization into lipid raft fractions upon cholesterol accumulation in NPC vs. wt cells. Furthermore, {gamma}-secretase inhibitor treatment significantly increased fl-APP/CTF distribution in raft fractions in NPC vs. wt cells, suggesting that upon cholesterol accumulation in NPC1-null cells increased formation of APP-CTF and its increased processing towards A{beta} occurs in lipid rafts. Our results support that cholesterol overload, such as in NPC disease, leads to increased partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic processing of APP in these cholesterol-rich membranes. This work adds to the mechanism of the cholesterol-effect on APP processing and the pathogenesis of Alzheimer's disease and supports the role of lipid rafts in these processes.

  12. Comparison of the outcome of burn patients using acute-phase plasma base deficit.

    PubMed

    Salehi, S H; As'adi, K; Mousavi, J

    2011-12-31

    Background. In recent years, plasma base deficit has been used as a marker to determine the status of tissue perfusion in trauma patients and also to predict the outcome of these patients. This study was performed to investigate the effect of plasma base deficit in predicting burn patient outcome. Methods. This prospective cohort study was performed from October 2009 to October 2010 in the acute phase of burn patients who were admitted within 6 h post-injury to Motahari Burn Hospital in Iran. The patients were divided into two groups based on the plasma base deficit in the first 24 h post-injury: group A, in which the mean plasma base deficit was less than or equal to -6 (more negative), and group B, in which the mean plasma base deficit greater than -6. Statistical analysis was performed using SPSS v.16 software. Results. Thirty-eight patients were enrolled in each group. The mean plasma base deficit in group A (-7.76 ± 2.18 mmol) was significantly less than that in group B (-1.19 ± 2.82) mmol (p < 0.05). Although there was no significant difference between the mean of fluid resuscitation and urine output in the first 24 h after injury between the two groups (p > 0.05) and despite removal of interfering factors, there were significant differences between the systemic inflammatory response syndrome and the multiple organ dysfunction syndrome score and the percentage of sepsis between the two groups (p < 0.05). The mortality rate in group A (63.2%) was significantly higher than that in group B (36.8%) (p > 0.05). Conclusion. The plasma base deficit can be used as a valuable marker in the resuscitation of burn patients, along with clinical criteria. Physiological indicators (burn percentage, age, and mucosal burns) are not sufficient to predict mortality and morbidity in burn patients, and it is necessary to investigate the role of biochemical markers such as base deficit in determining the final outcome of burn patients.

  13. Genetic Suppression of Transgenic APP Rescues Hypersynchronous Network Activity in a Mouse Model of Alzeimer's Disease

    PubMed Central

    Born, Heather A.; Kim, Ji-Yoen; Savjani, Ricky R.; Das, Pritam; Dabaghian, Yuri A.; Guo, Qinxi; Yoo, Jong W.; Schuler, Dorothy R.; Cirrito, John R.; Zheng, Hui; Golde, Todd E.; Noebels, Jeffrey L.

    2014-01-01

    Alzheimer's disease (AD) is associated with an elevated risk for seizures that may be fundamentally connected to cognitive dysfunction. Supporting this link, many mouse models for AD exhibit abnormal electroencephalogram (EEG) activity in addition to the expected neuropathology and cognitive deficits. Here, we used a controllable transgenic system to investigate how network changes develop and are maintained in a model characterized by amyloid β (Aβ) overproduction and progressive amyloid pathology. EEG recordings in tet-off mice overexpressing amyloid precursor protein (APP) from birth display frequent sharp wave discharges (SWDs). Unexpectedly, we found that withholding APP overexpression until adulthood substantially delayed the appearance of epileptiform activity. Together, these findings suggest that juvenile APP overexpression altered cortical development to favor synchronized firing. Regardless of the age at which EEG abnormalities appeared, the phenotype was dependent on continued APP overexpression and abated over several weeks once transgene expression was suppressed. Abnormal EEG discharges were independent of plaque load and could be extinguished without altering deposited amyloid. Selective reduction of Aβ with a γ-secretase inhibitor has no effect on the frequency of SWDs, indicating that another APP fragment or the full-length protein was likely responsible for maintaining EEG abnormalities. Moreover, transgene suppression normalized the ratio of excitatory to inhibitory innervation in the cortex, whereas secretase inhibition did not. Our results suggest that APP overexpression, and not Aβ overproduction, is responsible for EEG abnormalities in our transgenic mice and can be rescued independently of pathology. PMID:24623762

  14. Quantitation and localization of intracellular redox active metals by X-ray fluorescence microscopy in cortical neurons derived from APP and APLP2 knockout tissue

    SciTech Connect

    Ciccotosto, Giuseppe D.; James, Simon A.; Altissimo, Matteo; Paterson, David; Vogt, Stefan; Lai, Barry; de Jonge, Martin D.; Howard, Daryl L.; Bush, Ashley I.; Cappai, Roberto

    2014-10-01

    The amyloid precursor protein (APP) gene family includes APP and the amyloid precursor-like proteins, APLP1 and APLP2. These proteins contain metal binding sites for copper, zinc and iron and are known to have physiological roles in modulating the metal homeostasis in brain cells. Here we report the application of X-ray fluorescence microscopy (XFM) to investigate the subcellular distribution patterns of the metal ions Cu, Zn, Fe, and Ca in individual neurons derived from APP and APLP2 knockout mice brains to further define their role in metal homeostasis. These studies add to the growing body of data that the APP family of proteins are metalloproteins that have shared as well as distinct effects on metals. As we continue to delineate the cellular effects of the APP family of proteins it is important to consider how metals are involved in their actions.

  15. Quantitation and localization of intracellular redox active metals by X-ray fluorescence microscopy in cortical neurons derived from APP and APLP2 knockout tissue

    DOE PAGES

    Ciccotosto, Giuseppe D.; James, Simon A.; Altissimo, Matteo; Paterson, David; Vogt, Stefan; Lai, Barry; de Jonge, Martin D.; Howard, Daryl L.; Bush, Ashley I.; Cappai, Roberto

    2014-10-01

    The amyloid precursor protein (APP) gene family includes APP and the amyloid precursor-like proteins, APLP1 and APLP2. These proteins contain metal binding sites for copper, zinc and iron and are known to have physiological roles in modulating the metal homeostasis in brain cells. Here we report the application of X-ray fluorescence microscopy (XFM) to investigate the subcellular distribution patterns of the metal ions Cu, Zn, Fe, and Ca in individual neurons derived from APP and APLP2 knockout mice brains to further define their role in metal homeostasis. These studies add to the growing body of data that the APP familymore » of proteins are metalloproteins that have shared as well as distinct effects on metals. As we continue to delineate the cellular effects of the APP family of proteins it is important to consider how metals are involved in their actions.« less

  16. Altered APP Carboxyl-Terminal Processing Under Ferrous Iron Treatment in PC12 Cells

    PubMed Central

    Kim, Chi Hyun

    2013-01-01

    Amyloid-β peptide (Aβ), generated by proteolytic cleavage of the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). The key step in the generation of Aβ is cleavage of APP by beta-site APP-cleaving enzyme 1 (BACE1). Levels of BACE1 are increased in vulnerable regions of the AD brain, but the underlying mechanism is unknown. In the present study, we reported the effects of ferrous ions at subtoxic concentrations on the mRNA levels of BACE1 and a-disintegrin-and-metalloproteinase 10 (ADAM10) in PC12 cells and the cell responses to ferrous ions. The cell survival in PC12 cells significantly decreased with 0 to 0.3 mM FeCl2, with 0.6 mM FeCl2 treatment resulting in significant reductions by about 75%. 4,6-diamidino-2-phenylindole (DAPI) staining showed that the nuclei appeared fragmented in 0.2 and 0.3 mM FeCl2. APP-α-carboxyl terminal fragment (APP-α-CTF) associations with ADAM10 and APP-β-CTF with BACE1 were increased. Levels of ADAM10 and BACE1 mRNA increased in response to the concentrations of 0.25 mM, respectively. In addition, p-ERK and p-Bad (S112, S155) expressions were increased, suggesting that APP-CTF formation is related to ADAM10/BACE1 expression. Levels of Bcl-2 protein were increased, but significant changes were not observed in the expression of Bax. These data suggest that ion-induced enhanced expression of AMDA10/BACE1 could be one of the causes for APP-α/β-CTF activation. PMID:23776394

  17. There’s an App for That: Content Analysis of Paid Health and Fitness Apps

    PubMed Central

    Hall, P. Cougar; Hanson, Carl L; Barnes, Michael D; Giraud-Carrier, Christophe; Barrett, James

    2012-01-01

    Background The introduction of Apple’s iPhone provided a platform for developers to design third-party apps, which greatly expanded the functionality and utility of mobile devices for public health. Objective This study provides an overview of the developers’ written descriptions of health and fitness apps and appraises each app’s potential for influencing behavior change. Methods Data for this study came from a content analysis of health and fitness app descriptions available on iTunes during February 2011. The Health Education Curriculum Analysis Tool (HECAT) and the Precede-Proceed Model (PPM) were used as frameworks to guide the coding of 3336 paid apps. Results Compared to apps with a cost less than US $0.99, apps exceeding US $0.99 were more likely to be scored as intending to promote health or prevent disease (92.55%, 1925/3336 vs 83.59%, 1411/3336; P<.001), to be credible or trustworthy (91.11%, 1895/3336 vs 86.14%, 1454/3349; P<.001), and more likely to be used personally or recommended to a health care client (72.93%, 1517/2644 vs 66.77%, 1127/2644; P<.001). Apps related to healthy eating, physical activity, and personal health and wellness were more common than apps for substance abuse, mental and emotional health, violence prevention and safety, and sexual and reproductive health. Reinforcing apps were less common than predisposing and enabling apps. Only 1.86% (62/3336) of apps included all 3 factors (ie, predisposing, enabling, and reinforcing). Conclusions Development efforts could target public health behaviors for which few apps currently exist. Furthermore, practitioners should be cautious when promoting the use of apps as it appears most provide health-related information (predisposing) or make attempts at enabling behavior, with almost none including all theoretical factors recommended for behavior change. PMID:22584372

  18. Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs: A Toxicogenomic Study

    PubMed Central

    Halappanavar, Sabina; Jackson, Petra; Williams, Andrew; Jensen, Keld A; Hougaard, Karin S; Vogel, Ulla; Yauk, Carole L; Wallin, Håkan

    2011-01-01

    Titanium dioxide nanoparticles (nanoTiO2) are used in various applications including in paints. NanoTiO2 inhalation may induce pulmonary toxicity and systemic effects. However, the underlying molecular mechanisms are poorly understood. In this study, the effects of inhaled surface-coated nanoTiO2 on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL/6BomTac mice were exposed for 1 hr daily to 42.4 ± 2.9 (SEM) mg surface-coated nanoTiO2/m3 for 11 consecutive days by inhalation and were sacrificed 5 days following the last exposure. Physicochemical properties of the particles were determined. Pulmonary response to nanoTiO2 was characterized using DNA microarrays and pathway-specific PCR arrays and related to data on pulmonary inflammation from bronchial lavages. NanoTiO2 exposure resulted in increased levels of mRNA for acute phase markers serum amyloid A-1 (Saa1) and serum amyloid A-3 (Saa3), several C-X-C and C-C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more than 1.2-fold (adjusted P-value < 0.05) following exposure. Real time polymerase chain reaction confirmed the upregulation of miR-1, miR-449a and revealed dramatic induction of miR-135b (60-fold). Thus, inhalation of surface-coated nanoTiO2 results in changes in the expression of genes associated with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research. Environ. Mol. Mutagen., 2011. © 2011 Wiley-Liss, Inc.† PMID:21259345

  19. Brain plasmin enhances APP alpha-cleavage and Abeta degradation and is reduced in Alzheimer's disease brains.

    PubMed

    Ledesma, M D; Da Silva, J S; Crassaerts, K; Delacourte, A; De Strooper, B; Dotti, C G

    2000-12-01

    The proteolytic processing of amyloid precursor protein (APP) has been linked to sphingolipid-cholesterol microdomains (rafts). However, the raft proteases that may be involved in APP cleavage have not yet been identified. In this work we present evidence that the protease plasmin is restricted to rafts of cultured hippocampal neurons. We also show that plasmin increases the processing of human APP preferentially at the alpha-cleavage site, and efficiently degrades secreted amyloidogenic and non-amyloidogenic APP fragments. These results suggest that brain plasmin plays a preventive role in APP amyloidogenesis. Consistently, we show that brain tissue from Alzheimer's disease patients contains reduced levels of plasmin, implying that plasmin downregulation may cause amyloid plaque deposition accompanying sporadic Alzheimer's disease.

  20. PolyApps - Version 1.0

    SciTech Connect

    2010-08-05

    The polyApps software is an Umbra add-on C++ library that provides a polyhedral mesh library. Geometric shapes are defined by vertices, planes, edges, and faces. The library has a number of unique features that are useful for working with live scanners such as the SwissRanger. It includes a PolvApps multiple image texture casting capability that is compatible with the Umbra "Camera", and Umbra "lmageApps" class image connectors. The meshes are designed to be dynamic, allowing constant changing of their characteristics. Using these objects, live robot camera data can be cast onto arbitrary polygon meshes.

  1. PolyApps - Version 1.0

    2010-08-05

    The polyApps software is an Umbra add-on C++ library that provides a polyhedral mesh library. Geometric shapes are defined by vertices, planes, edges, and faces. The library has a number of unique features that are useful for working with live scanners such as the SwissRanger. It includes a PolvApps multiple image texture casting capability that is compatible with the Umbra "Camera", and Umbra "lmageApps" class image connectors. The meshes are designed to be dynamic, allowingmore » constant changing of their characteristics. Using these objects, live robot camera data can be cast onto arbitrary polygon meshes.« less

  2. Optimal processing for gel electrophoresis images: Applying Monte Carlo Tree Search in GelApp.

    PubMed

    Nguyen, Phi-Vu; Ghezal, Ali; Hsueh, Ya-Chih; Boudier, Thomas; Gan, Samuel Ken-En; Lee, Hwee Kuan

    2016-08-01

    In biomedical research, gel band size estimation in electrophoresis analysis is a routine process. To facilitate and automate this process, numerous software have been released, notably the GelApp mobile app. However, the band detection accuracy is limited due to a band detection algorithm that cannot adapt to the variations in input images. To address this, we used the Monte Carlo Tree Search with Upper Confidence Bound (MCTS-UCB) method to efficiently search for optimal image processing pipelines for the band detection task, thereby improving the segmentation algorithm. Incorporating this into GelApp, we report a significant enhancement of gel band detection accuracy by 55.9 ± 2.0% for protein polyacrylamide gels, and 35.9 ± 2.5% for DNA SYBR green agarose gels. This implementation is a proof-of-concept in demonstrating MCTS-UCB as a strategy to optimize general image segmentation. The improved version of GelApp-GelApp 2.0-is freely available on both Google Play Store (for Android platform), and Apple App Store (for iOS platform).

  3. The YeastGenome app: the Saccharomyces Genome Database at your fingertips.

    PubMed

    Wong, Edith D; Karra, Kalpana; Hitz, Benjamin C; Hong, Eurie L; Cherry, J Michael

    2013-01-01

    The Saccharomyces Genome Database (SGD) is a scientific database that provides researchers with high-quality curated data about the genes and gene products of Saccharomyces cerevisiae. To provide instant and easy access to this information on mobile devices, we have developed YeastGenome, a native application for the Apple iPhone and iPad. YeastGenome can be used to quickly find basic information about S. cerevisiae genes and chromosomal features regardless of internet connectivity. With or without network access, you can view basic information and Gene Ontology annotations about a gene of interest by searching gene names and gene descriptions or by browsing the database within the app to find the gene of interest. With internet access, the app provides more detailed information about the gene, including mutant phenotypes, references and protein and genetic interactions, as well as provides hyperlinks to retrieve detailed information by showing SGD pages and views of the genome browser. SGD provides online help describing basic ways to navigate the mobile version of SGD, highlights key features and answers frequently asked questions related to the app. The app is available from iTunes (http://itunes.com/apps/yeastgenome). The YeastGenome app is provided freely as a service to our community, as part of SGD's mission to provide free and open access to all its data and annotations. PMID:23396302

  4. Optimal processing for gel electrophoresis images: Applying Monte Carlo Tree Search in GelApp.

    PubMed

    Nguyen, Phi-Vu; Ghezal, Ali; Hsueh, Ya-Chih; Boudier, Thomas; Gan, Samuel Ken-En; Lee, Hwee Kuan

    2016-08-01

    In biomedical research, gel band size estimation in electrophoresis analysis is a routine process. To facilitate and automate this process, numerous software have been released, notably the GelApp mobile app. However, the band detection accuracy is limited due to a band detection algorithm that cannot adapt to the variations in input images. To address this, we used the Monte Carlo Tree Search with Upper Confidence Bound (MCTS-UCB) method to efficiently search for optimal image processing pipelines for the band detection task, thereby improving the segmentation algorithm. Incorporating this into GelApp, we report a significant enhancement of gel band detection accuracy by 55.9 ± 2.0% for protein polyacrylamide gels, and 35.9 ± 2.5% for DNA SYBR green agarose gels. This implementation is a proof-of-concept in demonstrating MCTS-UCB as a strategy to optimize general image segmentation. The improved version of GelApp-GelApp 2.0-is freely available on both Google Play Store (for Android platform), and Apple App Store (for iOS platform). PMID:27251892

  5. APP Overexpression Causes Aβ-Independent Neuronal Death through Intrinsic Apoptosis Pathway

    PubMed Central

    Cheng, Ning; Jiao, Song; Gumaste, Ankita; Bai, Li

    2016-01-01

    Abstract Accumulation of amyloid-β (Aβ) peptide in the brain is a central hallmark of Alzheimer’s disease (AD) and is thought to be the cause of the observed neurodegeneration. Many animal models have been generated that overproduce Aβ yet do not exhibit clear neuronal loss, questioning this Aβ hypothesis. We previously developed an in vivo mouse model that expresses a humanized amyloid precursor protein (hAPP) in olfactory sensory neurons (OSNs) showing robust apoptosis and olfactory dysfunction by 3 weeks of age, which is consistent with early OSN loss and smell deficits, as observed in AD patients. Here we show, by deleting the β-site APP cleaving enzyme 1 (BACE1) in two distinct transgenic mouse models, that hAPP-induced apoptosis of OSNs is Aβ independent and remains cell autonomous. In addition, we reveal that the intrinsic apoptosis pathway is responsible for hAPP-induced OSN death, as marked by mitochondrial damage and caspase-9 activation. Given that hAPP expression causes OSN apoptosis despite the absence of BACE1, we propose that Aβ is not the sole cause of hAPP-induced neurodegeneration and that the early loss of olfactory function in AD may be based on a cell-autonomous mechanism, which could mark an early phase of AD, prior to Aβ accumulation. Thus, the olfactory system could serve as an important new platform to study the development of AD, providing unique insight for both early diagnosis and intervention. PMID:27517085

  6. Loss of Polo ameliorates APP-induced Alzheimer’s disease-like symptoms in Drosophila

    PubMed Central

    Peng, Fei; Zhao, Yu; Huang, Xirui; Chen, Changyan; Sun, Lili; Zhuang, Luming; Xue, Lei

    2015-01-01

    The amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Despite extensive studies, little is known about the regulation of APP’s functions in vivo. Here we report that expression of human APP in Drosophila, in the same temporal-spatial pattern as its homolog APPL, induced morphological defects in wings and larval NMJ, larva and adult locomotion dysfunctions, male choice disorder and lifespan shortening. To identify additional genes that modulate APP functions, we performed a genetic screen and found that loss of Polo, a key regulator of cell cycle, partially suppressed APP-induced morphological and behavioral defects in larval and adult stages. Finally, we showed that eye-specific expression of APP induced retina degeneration and cell cycle re-entry, both phenotypes were mildly ameliorated by loss of Polo. These results suggest Polo is an important in vivo regulator of the pathological functions of APP, and provide insight into the role of cell cycle re-entry in AD pathogenesis. PMID:26597721

  7. APP Overexpression Causes Aβ-Independent Neuronal Death through Intrinsic Apoptosis Pathway.

    PubMed

    Cheng, Ning; Jiao, Song; Gumaste, Ankita; Bai, Li; Belluscio, Leonardo

    2016-01-01

    Accumulation of amyloid-β (Aβ) peptide in the brain is a central hallmark of Alzheimer's disease (AD) and is thought to be the cause of the observed neurodegeneration. Many animal models have been generated that overproduce Aβ yet do not exhibit clear neuronal loss, questioning this Aβ hypothesis. We previously developed an in vivo mouse model that expresses a humanized amyloid precursor protein (hAPP) in olfactory sensory neurons (OSNs) showing robust apoptosis and olfactory dysfunction by 3 weeks of age, which is consistent with early OSN loss and smell deficits, as observed in AD patients. Here we show, by deleting the β-site APP cleaving enzyme 1 (BACE1) in two distinct transgenic mouse models, that hAPP-induced apoptosis of OSNs is Aβ independent and remains cell autonomous. In addition, we reveal that the intrinsic apoptosis pathway is responsible for hAPP-induced OSN death, as marked by mitochondrial damage and caspase-9 activation. Given that hAPP expression causes OSN apoptosis despite the absence of BACE1, we propose that Aβ is not the sole cause of hAPP-induced neurodegeneration and that the early loss of olfactory function in AD may be based on a cell-autonomous mechanism, which could mark an early phase of AD, prior to Aβ accumulation. Thus, the olfactory system could serve as an important new platform to study the development of AD, providing unique insight for both early diagnosis and intervention. PMID:27517085

  8. Ear2 deletion causes early memory and learning deficits in APP/PS1 mice.

    PubMed

    Kummer, Markus P; Hammerschmidt, Thea; Martinez, Ana; Terwel, Dick; Eichele, Gregor; Witten, Anika; Figura, Stefanie; Stoll, Monika; Schwartz, Stephanie; Pape, Hans-Christian; Schultze, Joachim L; Weinshenker, David; Heneka, Michael T; Urban, Inga

    2014-06-25

    To assess the consequences of locus ceruleus (LC) degeneration and subsequent noradrenaline (NA) deficiency in early Alzheimer's disease (AD), mice overexpressing mutant amyloid precursor protein and presenilin-1 (APP/PS1) were crossed with Ear2(-/-) mice that have a severe loss of LC neurons projecting to the hippocampus and neocortex. Testing spatial memory and hippocampal long-term potentiation revealed an impairment in APP/PS1 Ear2(-/-) mice, whereas APP/PS1 or Ear2(-/-) mice showed only minor changes. These deficits were associated with distinct synaptic changes including reduced expression of the NMDA 2A subunit and increased levels of NMDA receptor 2B in APP/PS1 Ear2(-/-) mice. Acute pharmacological replacement of NA by L-threo-DOPS partially restored phosphorylation of β-CaMKII and spatial memory performance in APP/PS1 Ear2(-/-) mice. These changes were not accompanied by altered APP processing or amyloid β peptide (Aβ) deposition. Thus, early LC degeneration and subsequent NA reduction may contribute to cognitive deficits via CaMKII and NMDA receptor dysfunction independent of Aβ and suggests that NA supplementation could be beneficial in treating AD.

  9. Neospora caninum and Toxoplasma gondii: relationship between hepatic lesions, cytological and biochemical analysis of the cavitary liquid during the acute phase of the diseases in experimental models.

    PubMed

    Bottari, Nathieli B; Tonin, Alexandre A; Fighera, Rafael; Flores, Mariana M; França, Raqueli T; Camillo, Giovana; Toscan, Gustavo; Vogel, Fernanda S F; Sangoi, Manuela B; Bochi, Guilherme V; Moresco, Rafael N; Lopes, Sonia T A; Da Silva, Aleksandro S

    2014-01-01

    The objective of this study was to evaluate the pathogenesis of ascites in mice infected with Toxoplasma gondii and gerbils infected with Neospora caninum during the acute phase disease. For that, 12 gerbils [Experiment I: not infected/control (n=6) and infected (n=6)] and 12 mice [Experiment II: control (n=6) and infected (n=6)] were used. Infected gerbils and mice showed marked ascites on days 5-7 post-infection (PI), while the not-infected animals had not ascites. Peritoneal liquid was collected from the all mice with uninfected animals receiving 1.5mL of saline solution into their abdominal cavity, allowing the recovery of cavity liquid. As a result, it was possible to observe differences in physics, chemistry and cytological analysis of the fluid cavity of animals infected with N. caninum and T. gondii, when they were compared with uninfected animals, as well as between animals experimentally infected. Additionally both, N. caninum and T gondii, caused an increase in the levels of nitric oxide (NOx-nitrate/nitrite), protein oxidation (AOPP) and lipid peroxidation (TBARS), while serum total protein and albumin were reduced in infected gerbils and mice. Gerbils infected with N. caninum showed multiple large cells with multilobulated nucleus, lytic necrosis and abundant amount of eosinophilic cytoplasm into the hepatic parenchyma. By the other hand, mice infected with T. gondii developed myriad foci of lytic necrosis combined with tachyzoites and cysts containing bradyzoites in liver. Both experimental models for N. caninum and T. gondii showed inflammatory foci and tachyzoites the peritoneum, which could be a major cause of ascites. Toxoplasmosis and neosporosis were able to cause clinical signs in experimental models with similar alterations in peritoneal fluid; however the toxoplasmosis histological changes were much more evident. Therefore, the pathogenesis of ascites appears to be directly related to liver damage, which strongly suggests alteration in the

  10. Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region

    PubMed Central

    Kamino, Kouzin; Orr, Harry T.; Payami, Haydeh; Wijsman, Ellen M.; Alonso, Ma. Elisa; Pulst, Stefan M.; Anderson, Leojean; O'dahl, Sheldon; Nemens, Ellen; White, June A.; Sadovnick, Adele D.; Ball, Melvyn J.; Kaye, Jeffery; Warren, Andrew; McInnis, Melvin; Antonarakis, Stylianos E.; Korenberg, Julie R.; Sharma, Vikram; Kukull, Walter; Larson, Eric; Heston, Leonard L.; Martin, George M.; Bird, Thomas D.; Schellenberg, Gerard D.

    1992-01-01

    A large number of familial Alzheimer disease (FAD) kindreds were examined to determine whether mutations in the amyloid precursor protein (APP) gene could be responsible for the disease. Previous studies have identified three mutations at APP codon 717 which are pathogenic for Alzheimer disease (AD). Samples from affected subjects were examined for mutations in exons 16 and 17 of the APP gene. A combination of direct sequencing and single-strand conformational polymorphism analysis was used. Sporadic AD and normal controls were also examined by the same methods. Five sequence variants were identified. One variant at APP codon 693 resulted in a Glu→Gly change. This is the same codon as the hereditary cerebral hemorrhage with amyloidosis–Dutch type Glu→Gln mutation. Another single-base change at APP codon 708 did not alter the amino acid encoded at this site. Two point mutations and a 6-bp deletion were identified in the intronic sequences surrounding exon 17. None of the variants could be unambiguously determined to be responsible for FAD. The larger families were also analyzed by testing for linkage of FAD to a highly polymorphic short tandem repeat marker (D21S210) that is tightly linked to APP. Highly negative LOD scores were obtained for the family groups tested, and linkage was formally excluded beyond θ = .10 for the Volga German kindreds, θ = .20 for early-onset non-Volga Germans, and θ = .10 for late-onset families. LOD scores for linkage of FAD to markers centromeric to APP (D21S1/S11, D21S13, and D21S215) were also negative in the three family groups. These studies show that APP mutations account for AD in only a small fraction of FAD kindreds. ImagesFigure 4p1009-a PMID:1415269

  11. APP expression, distribution and accumulation are altered by aluminum in a rodent model for Alzheimer's disease.

    PubMed

    Walton, J R; Wang, M-X

    2009-11-01

    Up-regulated expression of amyloid precursor protein (APP) occurs early in the cascade of events that leads to amyloid plaque formation in the human brain. APP gene up-regulation, mediated by activated NF-kappaB, is a response to stress from nM concentrations of aluminum ions, aluminum-disregulated iron ions, reactive-oxygen species, cytokines, and physical trauma. We examined in vivo effects of aluminum on APP in aged rats, obtained from previously-reported longitudinal studies, that chronically ingested aluminum in amounts equivalent to total dietary aluminum levels that Americans routinely ingest. These rats exhibited two outcomes: one group remained cognitively-intact, scoring as well on a memory-discrimination task in old age as in middle age. The other developed cognitive deterioration, obtaining significantly lower mean performance scores in old age than in middle age and exhibiting abnormal behaviors associated with dementia. We compared the expression, distribution and accumulation of APP in hippocampal and cortical tissue of these two rat groups. Compared to results from cognitively-intact rats, hippocampal and cortical tissue from the cognitively-deteriorated rats showed elevated APP gene expression, significantly more dense APP deposits in cytoplasm of neural cells, and APP-immunoreactive neurites that were swollen and varicose. This study shows aluminum routinely derived from chronic oral ingestion, that gradually accumulates in brain regions important for memory-processing, is sufficient to increase APP levels in neural cells of those regions. Aluminum may thus launch the cascade that results in the formation of amyloid plaques in human brain.

  12. APP/PS1 transgenic mice treated with aluminum: an update of Alzheimer's disease model.

    PubMed

    Zhang, Q L; Jia, L; Jiao, X; Guo, W L; Ji, J W; Yang, H L; Niu, Q

    2012-01-01

    There is still no animal model available that can mimic all the cognitive, behavioral, biochemical, and histopathological abnormalities observed in patients with Alzheimer's disease (AD). We undertook to consider the interaction between genetic factors, including amyloid precursor protein (APP) and presenilin-1 (PS1), and environmental factors, such as Aluminum (Al) in determining susceptibility outcomes when studying the pathogenesis of AD. In this article, we provide an AD model in APP/PS1 transgenic mice triggered by Al. The animal model was established via intracerebral ventricular microinjection of aluminum chloride once a day for 5 days in APP/PS1 transgenic mice. Twenty wild type (WT) mice and 20 APP/PS1 transgenic (TG) mice were separately divided into 2 groups (control and Al group), and a stainless steel injector with stopper was used for microinjection into the left-lateral cerebral ventricle of each mouse. The Morris water maze task was used to evaluate behavioral function of learning and memory ability on the 20th day after the last injection. This AD model's brain was analyzed by: (1) amyloid beta immunohistochemical staining; (2) Tunnel staining; (3) apoptotic rates; (4) caspase-3 gene expression. Here, decrease of cognitive ability and neural cells loss were shown in APP/PS1 transgenic mice exposed to Al, which were more extensive than those in APP/PS1 TG alone and WT mice exposed to Al alone. These findings indicate that there is a close relationship between over-expression of APP and PS1 genes and Al overload. It is also suggested that APP/PS1 TG mice exposed to Al have potential value for improving AD models.

  13. Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region

    SciTech Connect

    Kamino, K.; Anderson, L.; O'dahl, S.; Nemens, E.; Bird, T.D.; Schellenberg, G.D.; Wijsman, E.M.; Kukall, W.; Larson, E. ); Heston, L.L.

    1992-11-01

    A large number of familial Alzheimer disease (FAD) kindreds were examined to determine whether mutations in the amyloid precursor protein (APP) gene could be responsible for the disease. Previous studies have identified three mutations at APP codon 717 which are pathogenic for Alzheimer disease (AD). Samples from affected subjects were examined for mutations in exons 16 and 17 of the APP gene. A combination of direct sequencing and single-strand conformational polymorphism analysis was used. Sporadic AD and normal controls were also examined by the same methods. Five sequence variants were identified. One variant at APP codon 693 resulted in a Glu[yields]Gly change. This is the same codon as the hereditary cerebral hemorrhage with amyloidosis-Dutch type Glu[yields]Gln mutation. Another single-base change at APP codon 708 did not alter the amino acid encoded at this site. Two point mutations and a 6-bp deletion were identified in the intronic sequences surrounding exon 17. None of the variants could be unambigously determined to be responsible for FAD. The larger families were also analyzed by testing for linkage of FAD to a highly polymorphic short tandem repeat marker (D21S210) that is tightly linked to APP. Highly negative LOD scores were obtained for the family groups tested, and linkage was formally excluded beyond [theta] = .10 for the Volga German kindreds, [theta] = .20 for early-onset non-Volga Germans, and [theta] = .10 for late-onset families. LOD scores for linkage of FAD to markers centromeric to APP (D21S1/S11, D21S13, and D21S215) were also negative in the three family groups. These studies show that APP mutations account for AD in only a small fraction of FAD kindreds. 49 refs., 6 figs., 4 tabs.

  14. Folic acid administration inhibits amyloid β-peptide accumulation in APP/PS1 transgenic mice.

    PubMed

    Li, Wen; Liu, Huan; Yu, Min; Zhang, Xumei; Zhang, Meilin; Wilson, John X; Huang, Guowei

    2015-08-01

    Alzheimer's disease (AD) is associated with malnutrition, altered one-carbon metabolism and increased hippocampal amyloid-β peptide (Aβ) accumulation. Aberrant DNA methylation may be an epigenetic mechanism that underlies AD pathogenesis. We hypothesized that folic acid acts through an epigenetic gene silencing mechanism to lower Aβ levels in the APP/PS1 transgenic mouse model of AD. APP/PS1 mice were fed either folate-deficient or control diets and gavaged daily with 120 μg/kg folic acid, 13.3mg/kg S-adenosylmethionine (SAM) or both. Examination of the mice after 60 days of treatment showed that serum folate concentration increased with intake of folic acid but not SAM. Folate deficiency lowered endogenous SAM concentration, whereas neither intervention altered S-adenosylhomocysteine concentration. DNA methyltransferase (DNMT) activity increased with intake of folic acid raised DNMT activity in folate-deficient mice. DNA methylation rate was stimulated by folic acid in the amyloid precursor protein (APP) promoter and in the presenilin 1 (PS1) promoter. Folate deficiency elevated hippocampal APP, PS1 and Aβ protein levels, and these rises were prevented by folic acid. In conclusion, these findings are consistent with a mechanism in which folic acid increases methylation potential and DNMT activity, modifies DNA methylation and ultimately decreases APP, PS1 and Aβ protein levels.

  15. From analogue to apps--developing an app to prepare children for medical imaging procedures.

    PubMed

    Williams, Gigi; Greene, Siobhan

    2015-01-01

    The Royal Children's Hospital (RCH) in Melbourne has launched a world-first app for children that will help reduce anxiety and the need for anesthesia during medical imaging procedures. The free, game-based app, "Okee in Medical Imaging", helps children aged from four to eight years to prepare for all medical imaging procedures--X-ray, CT, MRI, ultrasound, nuclear medicine, and fluoroscopy. The app is designed to reduce anticipatory fear of imaging procedures, while helping to ensure that children attend imaging appointments equipped with the skills required for efficient and effective scans to be performed. This paper describes how the app was developed. PMID:26828544

  16. From analogue to apps--developing an app to prepare children for medical imaging procedures.

    PubMed

    Williams, Gigi; Greene, Siobhan

    2015-01-01

    The Royal Children's Hospital (RCH) in Melbourne has launched a world-first app for children that will help reduce anxiety and the need for anesthesia during medical imaging procedures. The free, game-based app, "Okee in Medical Imaging", helps children aged from four to eight years to prepare for all medical imaging procedures--X-ray, CT, MRI, ultrasound, nuclear medicine, and fluoroscopy. The app is designed to reduce anticipatory fear of imaging procedures, while helping to ensure that children attend imaging appointments equipped with the skills required for efficient and effective scans to be performed. This paper describes how the app was developed.

  17. Acute phase response in the primiparous dairy cows after repeated percutaneous liver biopsy during the transition period.

    PubMed

    Jawor, P; Brzozowska, A; Słoniewski, K; Kowalski, Z M; Stefaniak, T

    2016-01-01

    The aim of this study was to evaluate the acute phase response of dairy cows to repeated liver biopsy in order to estimate the safety of this procedure during the transition period. Liver biopsies (up to 1000 mg of liver tissue) were conducted twice a day, 7 days before expected parturition and 3 days after calving. The number of needle insertions for each biopsy was recorded and was dependent on the amount of obtained tissue. Blood samples were taken on day 7 before expected parturition, then on days 3, 4, 7 and 14 after calving. Body temperature was measured daily in all 30 cows from day 3 until day 14 after calving. The concentrations of haptoglobin, serum amyloid A, fibrinogen and interleukin-6 were determined in serum and plasma. In 16.7% of cows, the rectal body temperature rose by ≥ 0.5°C on the day after liver biopsy. Although the concentrations of haptoglobin, serum amyloid A and fibrinogen increased significantly after calving (p<0.01), there was no influence of the number of biopsies on the acute phase reaction and repeated biopsy during the transition period had no effect on body temperature. Therefore, the procedure may be regarded as safe for cows during the transition period. PMID:27487515

  18. Hyperhomocysteinemia, a Biochemical Tool for Differentiating Ischemic and Nonischemic Central Retinal Vein Occlusion during the Early Acute Phase

    PubMed Central

    Mukherjee, Somnath; Ghosh, Sambuddha; Mukherjee, Suman; Dutta, Jayanta; Datta, Himadri; Das, Harendra Nath

    2015-01-01

    Purpose The purpose of the study was to differentiate ischemic central retinal vein occlusion (CRVO) from nonischemic CRVO during the early acute phase using plasma homocysteine as a biochemical marker. Methods Fasting plasma homocysteine, serum vitamin B12, and folate levels were measured in 108 consecutive unilateral elderly adult (age >50 years) ischemic CRVO patients in the absence of local and systemic disease and compared with a total of 144 age and sex matched nonischemic CRVO patients and 120 age and sex matched healthy control subjects. Results Homocysteine level was significantly increased in the patients with ischemic CRVO in comparison with nonischemic CRVO patients (p = 0.009) and also in comparison with control subjects (p < 0.001). Analysis also showed that hyperhomocysteinemia was associated with increased incidence of ischemic CRVO (odds ratio, 18) than that for nonischemic CRVO (odds ratio, 4.5). Serum vitamin B12 and folate levels were significantly lower (p < 0.001) in CRVO patients compared to the control but were not significantly different between nonischemic and ischemic CRVO patients (p > 0.1). Conclusions Hyperhomocysteinemia can be regarded as useful in differentiating nonischemic and ischemic CRVO during the early acute phase in absence of local and systemic disease in the elderly adult (age >50 years) population. PMID:25829824

  19. Nuclear trafficking, histone cleavage and induction of apoptosis by the meningococcal App and MspA autotransporters

    PubMed Central

    Khairalla, Ahmed S.; Omer, Sherko A.; Aslam, Akhmed; Dufailu, Osman A.; Self, Tim; Jonsson, Ann‐Beth; Geörg, Miriam; Sjölinder, Hong; Royer, Pierre‐Joseph; Martinez‐Pomares, Luisa; Ghaemmaghami, Amir M.; Wooldridge, Karl G.; Ala'Aldeen, Dlawer A.A.

    2015-01-01

    Summary N eisseria meningitidis, a major cause of bacterial meningitis and septicaemia, secretes multiple virulence factors, including the adhesion and penetration protein (App) and meningococcal serine protease A (MspA). Both are conserved, immunogenic, type Va autotransporters harbouring S6‐family serine endopeptidase domains. Previous work suggested that both could mediate adherence to human cells, but their precise contribution to meningococcal pathogenesis was unclear. Here, we confirm that App and MspA are in vivo virulence factors since human CD46‐expressing transgenic mice infected with meningococcal mutants lacking App, MspA or both had improved survival rates compared with mice infected with wild type. Confocal imaging showed that App and MspA were internalized by human cells and trafficked to the nucleus. Cross‐linking and enzyme‐linked immuno assay (ELISA) confirmed that mannose receptor (MR), transferrin receptor 1 (TfR1) and histones interact with MspA and App. Dendritic cell (DC) uptake could be blocked using mannan and transferrin, the specific physiological ligands for MR and TfR1, whereas in vitro clipping assays confirmed the ability of both proteins to proteolytically cleave the core histone H3. Finally, we show that App and MspA induce a dose‐dependent increase in DC death via caspase‐dependent apoptosis. Our data provide novel insights into the roles of App and MspA in meningococcal infection. PMID:25600171

  20. The Top Chinese Mobile Health Apps: A Systematic Investigation

    PubMed Central

    Hsu, Jeffrey; Liu, Di; Yu, Ya Min; Zhao, Hui Tong; Chen, Zhi Rou; Li, Jiao

    2016-01-01

    Background China’s mHealth market is on track to become a global leader by industry size. The Chinese mobile app market and health care system have peculiarities that distinguish them from other app markets. To date, Chinese mHealth apps have not been systematically investigated. Objective The objective of this study was to provide an overview of Chinese mHealth apps as of December 2015. Methods We identified and investigated the most downloaded apps from the iOS and Android platforms. For each app, we analyzed and recorded its main service offered, mHealth initiative, disease and specialty focus, app cost, target user, Web app availability, and emphasis on information security. Standard descriptive statistics were used. Results A total of 234 apps met the inclusion criteria and were investigated. The apps targeting nonhealth care professionals focused on providing telemedicine and appointment-making services. The apps targeting health care professionals focused on education and peer reviewed articles. The most common disease-specific apps focused primarily on diabetes, hypertension, and hepatitis management. Most apps were free and available on both iOS and Android platforms. Conclusions The primary mHealth initiatives targeted by the apps reflect Chinese patients’ demand for access to medical care. Disease-specific apps are also representative of disease prevalence in China. Government press releases suggest that new policies on the horizon may shift the industry. PMID:27573724

  1. Cloning and Expression of Phytase appA Gene from Shigella sp. CD2 in Pichia pastoris and Comparison of Properties with Recombinant Enzyme Expressed in E. coli

    PubMed Central

    Pal Roy, Moushree; Mazumdar, Deepika; Dutta, Subhabrata; Saha, Shyama Prasad; Ghosh, Shilpi

    2016-01-01

    The phytase gene appAS was isolated from Shigella sp. CD2 genomic library. The 3.8 kb DNA fragment contained 1299 bp open reading frame encoding 432 amino acid protein (AppAS) with 22 amino acid signal peptide at N-terminal and three sites of N-glycosylation. AppAS contained the active site RHGXRXP and HDTN sequence motifs, which are conserved among histidine acid phosphatases. It showed maximum identity with phytase AppA of Escherichia coli and Citrobacter braakii. The appAS was expressed in Pichia pastoris and E. coli to produce recombinant phytase rAppAP and rAppAE, respectively. Purified glycosylated rAppAP and nonglycosylated rAppAE had specific activity of 967 and 2982 U mg-1, respectively. Both had pH optima of 5.5 and temperature optima of 60°C. Compared with rAppAE, rAppAP was 13 and 17% less active at pH 3.5 and 7.5 and 11 and 18% less active at temperature 37 and 50°C, respectively; however, it was more active at higher incubation temperatures. Thermotolerance of rAppAP was 33% greater at 60°C and 24% greater at 70°C, when compared with rAppAE. Both the recombinant enzymes showed high specificity to phytate and resistance to trypsin. To our knowledge, this is the first report on cloning and expression of phytase from Shigella sp. PMID:26808559

  2. Finding a Depression App: A Review and Content Analysis of the Depression App Marketplace

    PubMed Central

    Shen, Nelson; Levitan, Michael-Jane; Johnson, Andrew; Bender, Jacqueline Lorene; Hamilton-Page, Michelle; Jadad, Alejandro (Alex) R

    2015-01-01

    Background Depression is highly prevalent and causes considerable suffering and disease burden despite the existence of wide-ranging treatment options. Mobile phone apps offer the potential to help close this treatment gap by confronting key barriers to accessing support for depression. Objectives Our goal was to identify and characterize the different types of mobile phone depression apps available in the marketplace. Methods A search for depression apps was conducted on the app stores of the five major mobile phone platforms: Android, iPhone, BlackBerry, Nokia, and Windows. Apps were included if they focused on depression and were available to people who self-identify as having depression. Data were extracted from the app descriptions found in the app stores. Results Of the 1054 apps identified by the search strategy, nearly one-quarter (23.0%, 243/1054) unique depression apps met the inclusion criteria. Over one-quarter (27.7%, 210/758) of the excluded apps failed to mention depression in the title or description. Two-thirds of the apps had as their main purpose providing therapeutic treatment (33.7%, 82/243) or psychoeducation (32.1%, 78/243). The other main purpose categories were medical assessment (16.9%, 41/243), symptom management (8.2%, 20/243), and supportive resources (1.6%, 4/243). A majority of the apps failed to sufficiently describe their organizational affiliation (65.0%, 158/243) and content source (61.7%, 150/243). There was a significant relationship (χ 2 5=50.5, P<.001) between the main purpose of the app and the reporting of content source, with most medical assessment apps reporting their content source (80.5%, 33/41). A fifth of the apps featured an e-book (20.6%, 50/243), audio therapy (16.9%, 41/243), or screening (16.9%, 41/243) function. Most apps had a dynamic user interface (72.4%, 176/243) and used text as the main type of media (51.9%, 126/243), and over a third (14.4%, 35/243) incorporated more than one form of media. Conclusion

  3. Markers of iron status are associated with stage of pregnancy and acute-phase response, but not with parity among pregnant women in Guinea-Bissau.

    PubMed

    Kæstel, Pernille; Aaby, Peter; Ritz, Christian; Friis, Henrik

    2015-10-14

    While prenatal Fe supplementation prevents maternal Fe deficiency and anaemia, it is uncertain whether it improves infant health outcomes, at least when taken by Fe-replete women. Inflammation as well as physiological changes complicates the assessment of Fe status during pregnancy. In the present study, we measured the concentrations of serum ferritin and soluble transferrin receptors (sTfR), Hb and the acute-phase proteins C-reactive protein (CRP) and α1-antichymotrypsin (ACT) in a cross-sectional study among 738 pregnant women attending antenatal care in Guinea-Bissau, West Africa. Multiple linear regression analysis was used to identify the predictors of Fe status markers. The mean gestational age was 23 (sd 7) weeks. Serum ferritin values were lower with progressing gestation, from 27% lower during weeks 16-20 of gestation up to 59% lower after 29 weeks of gestation compared with early pregnancy. Using cut-off values for Fe deficiency as established in non-pregnant individuals, 52% of the women had sTfR levels >2·3 mg/l, while only 25% had serum ferritin levels 2·3 mg/l decreased to 47% after adjustment for elevated serum CRP and ACT levels. On the contrary, the proportion of serum ferritin < 12 μg/l increased to 33% after adjustment for ACT and CRP. The high proportion of elevated serum sTfR calls for pregnancy-specific cut-offs since increased erythropoiesis is expected in response to increased plasma volume of pregnancy. The present study further underlines the need to adjust for inflammation when serum sTfR and serum ferritin are used to assess Fe status in pregnancy.

  4. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease.

    PubMed

    Poulsen, Sarah S; Saber, Anne T; Mortensen, Alicja; Szarek, Józef; Wu, Dongmei; Williams, Andrew; Andersen, Ole; Jacobsen, Nicklas R; Yauk, Carole L; Wallin, Håkan; Halappanavar, Sabina; Vogel, Ulla

    2015-03-15

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162μg/mouse of small, entangled (CNTSmall, 0.8±0.1μm long) or large, thick MWCNTs (CNTLarge, 4±0.4μm long). Liver tissues and plasma were harvested 1, 3 and 28days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease.

  5. APP anterograde transport requires Rab3A GTPase activity for assembly of the transport vesicle

    PubMed Central

    Szodorai, A; Kuan, Y-H; Hunzelmann, S; Engel, U; Sakane, A; Sasaki, T; Takai, Y; Kirsch, J; Müller, U; Beyreuther, K; Brady, S; Morfini, G; Kins, S

    2010-01-01

    The amyloid precursor protein (APP) may be sequentially cleaved by β- and γ-secretases leading to accumulation of Aβ peptides in brains of Alzheimer’s Disease patients. Cleavage by α-secretase prevents Aβ generation. APP is anterogradely transported by conventional kinesin in a distinct transport vesicle, but both the biochemical composition of such a vesicle as well as the specific kinesin-1 motor responsible for transport are poorly defined. Here, we demonstrate by time-lapse analysis and immunoisolations that APP is a cargo of a vesicle containing the kinesin heavy chain isoform kinesin-1C, the small GTPase Rab3A and a specific subset of presynaptic protein components. Moreover, we report that assembly of kinesin-1C and APP in this vesicle type requires Rab3A GTPase activity. Finally, we show cleavage of APP in the analyzed transport vesicles by α-secretase activity, likely mediated by ADAM10. Together, these data indicate for the first time that maturation of transport vesicles, including coupling of conventional kinesin, requires Rab GTPase activity. PMID:19923287

  6. Planet App: Kids' Book Apps Are Everywhere. But Are They Any Good?

    ERIC Educational Resources Information Center

    Bird, Elizabeth

    2011-01-01

    A proper picture book app lets a parent and child read, listen to, or explore a book in a fun and interactive manner. Typical options offered in these apps include turning off the sound (so that a parent or child can read on their own), changing from one language to another, and small interactive features, such as making the characters move. To…

  7. Mobile App Rating Scale: A New Tool for Assessing the Quality of Health Mobile Apps

    PubMed Central

    Kavanagh, David J; Zelenko, Oksana; Tjondronegoro, Dian; Mani, Madhavan

    2015-01-01

    Background The use of mobile apps for health and well being promotion has grown exponentially in recent years. Yet, there is currently no app-quality assessment tool beyond “star”-ratings. Objective The objective of this study was to develop a reliable, multidimensional measure for trialling, classifying, and rating the quality of mobile health apps. Methods A literature search was conducted to identify articles containing explicit Web or app quality rating criteria published between January 2000 and January 2013. Existing criteria for the assessment of app quality were categorized by an expert panel to develop the new Mobile App Rating Scale (MARS) subscales, items, descriptors, and anchors. There were sixty well being apps that were randomly selected using an iTunes search for MARS rating. There were ten that were used to pilot the rating procedure, and the remaining 50 provided data on interrater reliability. Results There were 372 explicit criteria for assessing Web or app quality that were extracted from 25 published papers, conference proceedings, and Internet resources. There were five broad categories of criteria that were identified including four objective quality scales: engagement, functionality, aesthetics, and information quality; and one subjective quality scale; which were refined into the 23-item MARS. The MARS demonstrated excellent internal consistency (alpha = .90) and interrater reliability intraclass correlation coefficient (ICC = .79). Conclusions The MARS is a simple, objective, and reliable tool for classifying and assessing the quality of mobile health apps. It can also be used to provide a checklist for the design and development of new high quality health apps. PMID:25760773

  8. Exhaled Nitric Oxide in Acute Phase of Bronchiolitis and Its Relation with Episodes of Subsequent Wheezing in Children of Preschool Age

    PubMed Central

    Osona, Borja; Gil-Sanchez, Jose Antonio; Figuerola, Joan

    2012-01-01

    Background Fractional exhaled nitric oxide (FENO) levels are increased in children with asthma and in infants with recurrent wheezing, but the role of FENO in the acute phase of bronchiolitis is still not defined. Objective The aim of this study is to evaluate FENO values in the acute phase of bronchiolitis, compare them with healthy infants, and relate those values with the appearance of other wheezing episodes. Methods FENO values were determined in infants between 2 months and 2 years affected with RVS bronchiolitis by offline method. The FENO values collected in the acute phase were related with the respiratory clinical symptoms presented in the 2 years following the episode. Results A total of 30 patients were recruited: 15 in the bronchiolitis group and 15 in the control group. The average of the FENO values in the acute phase was 18.74 ppb (range 2–88) in the bronchiolitis group, and 8.75 ppb (range 2–24) in the control group. However, these results showed no significant statistical differences (p=0.176). Nevertheless, we found a positive correlation between the FENO values and the clinical score (Downes) of the bronchiolitis episode (p=0.023). In infants that presented other wheezing episodes in the 2 years after, the average of FENO in the acute phase of the first episode was 23.1 ppb (average of 10.25 ppb) versus 8.4 ppb (average 5.4 ppb) in the group of patients with no other episodes. The comparison of averages has no statistical significance. Conclusion We found no differences in FENO between infants with bronchiolitis and healthy ones. The FENO values in the acute phase seems to be related to the severity of the disease but do not predict the appearance of wheezing episodes in the following 2 years. PMID:22768386

  9. App Store for EHRs and Patients Both.

    PubMed

    Franckle, Travers; Haas, Daniel; Mandl, Kenneth D

    2013-01-01

    The Substitutable Medical Applications, Reusable Technologies (SMART) Platforms project ( www.smartplatforms.org ) seeks to develop an iPhone-like health information technology platform with substitutable apps constructed around core services. It is funded by a grant from the Office of the National Coordinator of Health Information Technology's Strategic Health IT Advanced Research Projects (SHARP) Program. SMART technologies enable existing electronic health records and HIT platforms to run substitutable apps. Substitutability is the capability inherent in a system of replacing one application with another of similar functionality. We created a patient-facing SMART instance using the open source Indivo personally controlled health record (PCHR). The SMART "read-only" API has been deployed on multiple systems, including the Cerner installation at Boston Children's Hospital and the World Vista EHR. We sought to SMART-enable Indivo, the open source reference PCHR upon which HealthVault and other PCHRs were modeled. PCHRs provide patients with a secure repository of their health information that can be exposed to apps across a programming interface. We updated the open source Indivo PCHR to support the SMART API, enabling Indivo to act as a patient-facing apps platform, running the same or similar versions of apps that face clinicians.

  10. App Store for EHRs and Patients Both.

    PubMed

    Franckle, Travers; Haas, Daniel; Mandl, Kenneth D

    2013-01-01

    The Substitutable Medical Applications, Reusable Technologies (SMART) Platforms project ( www.smartplatforms.org ) seeks to develop an iPhone-like health information technology platform with substitutable apps constructed around core services. It is funded by a grant from the Office of the National Coordinator of Health Information Technology's Strategic Health IT Advanced Research Projects (SHARP) Program. SMART technologies enable existing electronic health records and HIT platforms to run substitutable apps. Substitutability is the capability inherent in a system of replacing one application with another of similar functionality. We created a patient-facing SMART instance using the open source Indivo personally controlled health record (PCHR). The SMART "read-only" API has been deployed on multiple systems, including the Cerner installation at Boston Children's Hospital and the World Vista EHR. We sought to SMART-enable Indivo, the open source reference PCHR upon which HealthVault and other PCHRs were modeled. PCHRs provide patients with a secure repository of their health information that can be exposed to apps across a programming interface. We updated the open source Indivo PCHR to support the SMART API, enabling Indivo to act as a patient-facing apps platform, running the same or similar versions of apps that face clinicians. PMID:24303239

  11. Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging

    PubMed Central

    Guo, Xiaoli; He, Yongzhi; Lu, Hongyang; Li, Yao; Su, Xin; Jiang, Ying; Tong, Shanbao

    2016-01-01

    The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours) after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input. PMID:27144032

  12. Early Diagnosis of Congenital Trypanosoma cruzi Infection, Using Shed Acute Phase Antigen, in Ushuaia, Tierra del Fuego, Argentina

    PubMed Central

    Mallimaci, María Cristina; Sosa-Estani, Sergio; Russomando, Graciela; Sanchez, Zunilda; Sijvarger, Carina; Alvarez, Isabel Marcela; Barrionuevo, Lola; Lopez, Carlos; Segura, Elsa Leonor

    2010-01-01

    Chagas' disease, or American trypanosomiasis, is caused by the protozoan parasite Trypanasoma cruzi. It is estimated that 15,000 new cases of congenital T. cruzi transmission occur in the Americas each year. The aim of this study was to estimate the rate of congenital T. cruzi infection in infants born to infected women living in Ushuaia, Argentina, as well to assess a serologic test using Shed Acute Phase Antigen (SAPA) for a timely diagnosis of congenital infection. The rate of congenital infection among children in the study was 4.4% (3/68). Our results show that for infants younger than 30 days of age, matched blood samples from mother and infant were capable of identifying congenital transmission of infection using an enzyme-linked immunosorbent assay with SAPA. For infants older than 3 months, congenital infection could be ruled out using the same procedure. PMID:20064996

  13. SHARED, NOT UNIQUE, COMPONENTS OF PERSONALITY AND PSYCHOSOCIAL FUNCTIONING PREDICT DEPRESSION SEVERITY AFTER ACUTE-PHASE COGNITIVE THERAPY

    PubMed Central

    Clark, Lee Anna; Vittengl, Jeffrey R.; Kraft, Dolores; Jarrett, Robin B.

    2005-01-01

    In a sample of 100 patients with recurrent major depression, we collected depression severity data early and late in acute-phase cognitive therapy, plus a wide range of psychosocial variables that have been studied extensively in depression research, including measures of interpersonal, cognitive, and social functioning, and personality traits using an inventory that is linked with the Big-Three tradition in personality assessment theory. By assessing this broad range of variables in a single study, we could examine the extent to which relations of these variables with depression were due to (a) a common factor shared across this diverse set of constructs, (b) factors shared among each type of construct (personality vs. psychosocial measures), or (c) specific aspects of the individual measures. Only the most general factor shared across the personality and psychosocial variables predicted later depression. PMID:14632375

  14. Early diagnosis of congenital Trypanosoma cruzi infection, using shed acute phase antigen, in Ushuaia, Tierra del Fuego, Argentina.

    PubMed

    Mallimaci, María Cristina; Sosa-Estani, Sergio; Russomando, Graciela; Sanchez, Zunilda; Sijvarger, Carina; Alvarez, Isabel Marcela; Barrionuevo, Lola; Lopez, Carlos; Segura, Elsa Leonor

    2010-01-01

    Chagas' disease, or American trypanosomiasis, is caused by the protozoan parasite Trypanasoma cruzi. It is estimated that 15,000 new cases of congenital T. cruzi transmission occur in the Americas each year. The aim of this study was to estimate the rate of congenital T. cruzi infection in infants born to infected women living in Ushuaia, Argentina, as well to assess a serologic test using Shed Acute Phase Antigen (SAPA) for a timely diagnosis of congenital infection. The rate of congenital infection among children in the study was 4.4% (3/68). Our results show that for infants younger than 30 days of age, matched blood samples from mother and infant were capable of identifying congenital transmission of infection using an enzyme-linked immunosorbent assay with SAPA. For infants older than 3 months, congenital infection could be ruled out using the same procedure.

  15. Beebook: light field mapping app

    NASA Astrophysics Data System (ADS)

    De Donatis, Mauro; Di Pietro, Gianfranco; Rinnone, Fabio

    2014-05-01

    In the last decade the mobile systems for field digital mapping were developed (see Wikipedia for "Digital geologic mapping"), also against many skeptic traditional geologists. Until now, hardware was often heavy (tablet PC) and software sometime difficult also for expert GIS users. At present, the advent of light tablet and applications makes things easier, but we are far to find a whole solution for a complex survey like the geological one where you have to manage complexities such information, hypothesis, data, interpretation. Beebook is a new app for Android devices, has been developed for fast ad easy mapping work in the field trying to try to solve this problem. The main features are: • off-line raster management, GeoTIFF ed other raster format using; • on-line map visualisation (Google Maps, OSM, WMS, WFS); • SR management and conversion using PROJ.4; • vector file mash-up (KML and SQLite format); • editing of vector data on the map (lines, points, polygons); • augmented reality using "Mixare" platform; • export of vector data in KML, CSV, SQLite (Spatialite) format; • note: GPS or manual point inserting linked to other application files (pictures, spreadsheet, etc.); • form: creation, edition and filling of customized form; • GPS: status control, tracker and positioning on map; • sharing: synchronization and sharing of data, forms, positioning and other information can be done among users. The input methods are different from digital keyboard to fingers touch, from voice recording to stylus. In particular the most efficient way of inserting information is the stylus (or pen): field geologists are familiar with annotation and sketches. Therefore we suggest the use of devices with stylus. The main point is that Beebook is the first "transparent" mobile GIS for tablet and smartphone deriving from previous experience as traditional mapping and different previous digital mapping software ideation and development (MapIT, BeeGIS, Geopaparazzi

  16. The influence of supplemental chromium and vaccines on the acute phase response of newly arrived feeder calves.

    PubMed Central

    Wright, A J; Mallard, B A; Mowat, D N

    1995-01-01

    The acute phase response as indicated by serum haptoglobin and total haemolytic complement activity (CH50) was measured in 72 cross-bred steer calves purchased at sales in Ontario. During the 28 day (d) trial, 18 steers were randomly assigned to each of the following groups: 1) control; 2) vaccinated (Infectious Bovine Rhinotracheitis, Parainfluenza-3, Bovine Viral Diarrhea, Bovine Respiratory Synctial Virus vaccine plus Pasteurella haemolytica vaccine); 3) supplemental chelated Cr (0.14 mg/kg); and 4) Cr plus vaccines. Haptoglobin concentrations were low at arrival, increased (P < 0.05) on day 7, and returned to near initial levels (P > 0.05) by day 14. Supplemental Cr reduced (P < 0.05) haptoglobin on day 7 when morbidity was highest. Following antibiotic treatment for respiratory disease haptoglobin was lower (P < 0.05) than during morbidity; however, during morbidity, haptoglobin concentrations were not greater in sick calves (P > 0.05) than in healthy calves. Complement activity was lowest on day 7 (P < 0.05) and peaked on day 14 (P < 0.05). Complement activity tended to be lower on day 7 for vaccine, Cr, and Cr+ vaccine groups; however, the difference from controls was not significant (P > 0.10). Complement activity did not increase on day 14 (P > 0.05) with Cr supplementation as in other treatments. Morbid calves had lower (P < 0.05) CH50 activity than healthy calves on day 14. Following antibiotic treatment, the Cr-supplemented group had higher (P < 0.05) CH50 than during morbidity. In general, chromium supplementation reduced the acute phase response in newly arrived feeder calves. PMID:8548694

  17. Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice

    PubMed Central

    Cui, Hao; Hung, Amos C.; Klaver, David W.; Suzuki, Toshiharu; Freeman, Craig; Narkowicz, Christian; Jacobson, Glenn A.; Small, David H.

    2011-01-01

    Background Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice. Methodology/Principal Findings We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17. Conclusions/Significance The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study. PMID:21829577

  18. APP intracellular domain-WAVE1 pathway reduces amyloid-β production.

    PubMed

    Ceglia, Ilaria; Reitz, Christiane; Gresack, Jodi; Ahn, Jung-Hyuck; Bustos, Victor; Bleck, Marina; Zhang, Xiaozhu; Martin, Grant; Simon, Sanford M; Nairn, Angus C; Greengard, Paul; Kim, Yong

    2015-09-01

    An increase in amyloid-β (Aβ) production is a major pathogenic mechanism associated with Alzheimer's disease (AD), but little is known about possible homeostatic control of the amyloidogenic pathway. Here we report that the amyloid precursor protein (APP) intracellular domain (AICD) downregulates Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 1 (WAVE1 or WASF1) as part of a negative feedback mechanism to limit Aβ production. The AICD binds to the Wasf1 promoter, negatively regulates its transcription and downregulates Wasf1 mRNA and protein expression in Neuro 2a (N2a) cells. WAVE1 interacts and colocalizes with APP in the Golgi apparatus. Experimentally reducing WAVE1 in N2a cells decreased the budding of APP-containing vesicles and reduced cell-surface APP, thereby reducing the production of Aβ. WAVE1 downregulation was observed in mouse models of AD. Reduction of Wasf1 gene expression dramatically reduced Aβ levels and restored memory deficits in a mouse model of AD. A decrease in amounts of WASF1 mRNA was also observed in human AD brains, suggesting clinical relevance of the negative feedback circuit involved in homeostatic regulation of Aβ production. PMID:26280122

  19. A role for secretory phospholipase A2 and C-reactive protein in the removal of injured cells.

    PubMed

    Hack, C E; Wolbink, G J; Schalkwijk, C; Speijer, H; Hermens, W T; van den Bosch, H

    1997-03-01

    The acute phase response is initiated in response to infection or physical trauma and is characterized by an increase in the levels of some plasma proteins. Here, Erik Hack and colleagues suggest that the combined actions of two of these acute phase proteins, secretory phospholipase A2 and C-reactive protein, may serve to promote phagocytosis of injured cells and tissue debris, thereby enhancing inflammation and tissue damage.

  20. The "Free from Housing Accessibility Problems" App.

    PubMed

    Jonsson, Oskar; Slaug, Björn; Haak, Maria; Mårtensson, Knut; Schmidt, Steven M; Oswald, Frank; Rimland, Joseph M; Tomsone, Signe; Svensson, Torbjörn; Iwarsson, Susanne

    2016-01-01

    The present study concerns the development of a computerized tool targeting housing accessibility issues. A user-centered approach involving professionals from the housing sector and senior citizens from four European countries resulted in a fully functional prototype of a mobile application (app) including an apartment database. The app raises awareness on housing accessibility and has the potential to support decision making and strengthen all citizens regardless of functional capacity to be more active in their endeavors for a satisfying housing solution. Further refinements and additional features are needed to enhance the potential benefits; they include addressing potential challenges facing senior citizens, developing interactive features that allow users to provide input and adapting to different national contexts to make the app applicable for the European market. PMID:27534351

  1. Peri-infarct zone characterized by cardiac magnetic resonance imaging is directly associated with the inflammatory activity during acute phase myocardial infarction.

    PubMed

    Quinaglia e Silva, Jose C; Coelho-Filho, Otavio Rizzi; Andrade, Joalbo M; Quinaglia, Thiago; Modolo, Rodrigo G P; Almeida, Breno O; van der Geest, Rob J; Jerosch-Herold, Michael; Coelho, Otavio Rizzi; Sposito, Andrei C

    2014-06-01

    Enhanced systemic inflammatory activity (SIA) during myocardial infarction (MI) and the extent of the peri-infarct zone characterized by cardiac magnetic resonance imaging (CMRi) are both associated with increased risk of life-threatening arrhythmias and sudden cardiac death. The present study investigated the existence of association between these two phenomena in 98 patients (55 ± 10 years) with ST segment elevation MI. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), and tumor necrosis factor (TNF) were measured on admission (D1) and on the fifth day post-MI (D5). CMRi was performed 2 weeks after MI to quantify peri-infarct zone (PIZ). Between D1 and D5, the increase in CRP (6.0 vs. 5.6 times; p = 0.02), IL-2 (3.6 vs. 3.4 times; p = 0.04) and tumor necrosis factor type α (TNF-α; 4.6 vs. 3.9 times; p = 0.001) were higher in patients with PIZ above the median than in the counterparts. PIZ was correlated with CRP-D5 (r = 0.69), delta-CRP (r = 0.7), IL-2-D5 (r = 0.5), delta-IL-2 (r = 0.6), TNF-α (r = 0.5), delta-TNF-α (r = 0.4; p = 0.0001). Enhanced activation of SIA during the acute phase of MI is directly related with generation of PIZ.

  2. Hepatic and Pulmonary Toxicogenomic Profiles in Mice Intratracheally Instilled With Carbon Black Nanoparticles Reveal Pulmonary Inflammation, Acute Phase Response, and Alterations in Lipid Homeostasis

    PubMed Central

    Bourdon, Julie A.; Halappanavar, Sabina; Saber, Anne T.; Jacobsen, Nicklas R.; Williams, Andrew; Wallin, Håkan; Vogel, Ulla; Yauk, Carole L.

    2012-01-01

    Global pulmonary and hepatic messenger RNA profiles in adult female C57BL/6 mice intratracheally instilled with carbon black nanoparticles (NPs) (Printex 90) were analyzed to identify biological perturbations underlying systemic responses to NP exposure. Tissue gene expression changes were profiled 1, 3, and 28 days following exposure to 0.018, 0.054, and 0.162 mg Printex 90 alongside controls. Pulmonary response was marked by increased expression of inflammatory markers and acute phase response (APR) genes that persisted to day 28 at the highest exposure dose. Genes in the 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase pathway were increased, and those involved in cholesterol efflux were decreased at least at the highest dose on days 1 and 3. Hepatic responses mainly consisted of the HMG-CoA reductase pathway on days 1 (high dose) and 28 (all doses). Protein analysis in tissues and plasma of 0.162 mg Printex 90–exposed mice relative to control revealed an increase in plasma serum amyloid A on days 1 and 28 (p < 0.05), decreases in plasma high-density lipoprotein on days 3 and 28, an increase in plasma low-density lipoprotein on day 28 (p < 0.05), and marginal increases in total hepatic cholesterol on day 28 (p = 0.06). The observed changes are linked to APR. Although further research is needed to establish links between observations and the onset and progression of systemic disorders, the present study demonstrates the ability of NPs to induce systemic effects. PMID:22461453

  3. Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis.

    PubMed

    Oezcueruemez-Porsch, M; Kunz, D; Hardt, P D; Fadgyas, T; Kress, O; Schulz, H U; Schnell-Kretschmer, H; Temme, H; Westphal, S; Luley, C; Kloer, H U

    1998-08-01

    Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been suggested as a model for acute pancreatitis (AP), which allows evaluation of early alterations in the time course of the disease. The influence of the clinical course on procalcitonin (PCT), serum amyloid A (SAA), and several proinflammatory and inhibitory cytokines was evaluated in patients with AP following ERCP. Blood samples were prospectively collected from patients undergoing ERCP. The incidence of ERCP-induced pancreatic damage, defined as abdominal complaints, a threefold increase of serum lipase, and elevation of CRP from <10 to >20 mg/liter was 12.8% (12/94). Only mild clinical courses of acute pancreatitis were observed. PCT significantly increased in subjects with post-ERCP pancreatitis after 24 hr. However, PCT levels did not exceed 0.5 ng/ml in any patient. Interleukin-1 receptor antagonist (IL-1RA) began to differ from baseline 2 hr after ERCP, followed by interleukin-6 (IL-6, 6 hr), solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII, 24 hr) and SAA (24 hr). Interleukin 10 (IL-10) showed marked interindividual variations with no obvious peak. Among all parameters evaluated, only peak values of IL-6 and IL-10 showed significant correlations with the reported pain score (r2 = 0.62/0.78), degree of ampullar irritation (r2 = NS/0.87), and the duration of ERCP (r2 = 0.58/0.76). No correlation was found with the volume of the injected contrast agent. We conclude that IL-10 and IL-6 appear to be useful to monitor patients after ERCP. The absence of any PCT elevation in the present study is in accordance with the clinical course of the patients who suffered from mild pancreatic damage without systemic or infectious complications.

  4. Compliance of blood donation apps with mobile OS usability guidelines.

    PubMed

    Ouhbi, Sofia; Fernández-Alemán, José Luis; Pozo, José Rivera; Bajta, Manal El; Toval, Ambrosio; Idri, Ali

    2015-06-01

    The aim of this paper is to employ the guidelines of Android, iOS, Blackberry and Windows Phone to analyze the usability compliance of free blood donation (BD) apps. An analysis process based on a systematic review protocol is used to select free BD apps. An assessment is conducted using a questionnaire composed of 13 questions concerning the compliance of free BD apps with Android, Blackberry, iOS and Windows Phone usability guidelines. A total of 133 free BD apps have been selected from the 188 BD apps identified. Around 63% of the free BD apps selected have a good compliance with mobile OS usability recommendations. Around 72% of Android, 57% of Windows Phone, 33% of iOS and 33% of Blackberry BD apps have a high usability score. The aspect of BD app behavior should be improved along with some style components: the use of pictures to explain ideas and the adaptation of the app to both horizontal and vertical orientations. Structure patterns should also be used to improve the structure aspect of a BD app. Usability is a quality aspect that should be improved in current BD apps. Our study provides smartphone users with a list of usable free BD apps and BD app developers with recommendations. PMID:25845672

  5. Compliance of blood donation apps with mobile OS usability guidelines.

    PubMed

    Ouhbi, Sofia; Fernández-Alemán, José Luis; Pozo, José Rivera; Bajta, Manal El; Toval, Ambrosio; Idri, Ali

    2015-06-01

    The aim of this paper is to employ the guidelines of Android, iOS, Blackberry and Windows Phone to analyze the usability compliance of free blood donation (BD) apps. An analysis process based on a systematic review protocol is used to select free BD apps. An assessment is conducted using a questionnaire composed of 13 questions concerning the compliance of free BD apps with Android, Blackberry, iOS and Windows Phone usability guidelines. A total of 133 free BD apps have been selected from the 188 BD apps identified. Around 63% of the free BD apps selected have a good compliance with mobile OS usability recommendations. Around 72% of Android, 57% of Windows Phone, 33% of iOS and 33% of Blackberry BD apps have a high usability score. The aspect of BD app behavior should be improved along with some style components: the use of pictures to explain ideas and the adaptation of the app to both horizontal and vertical orientations. Structure patterns should also be used to improve the structure aspect of a BD app. Usability is a quality aspect that should be improved in current BD apps. Our study provides smartphone users with a list of usable free BD apps and BD app developers with recommendations.

  6. The familial Alzheimer's disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons

    PubMed Central

    Muratore, Christina R.; Rice, Heather C.; Srikanth, Priya; Callahan, Dana G.; Shin, Taehwan; Benjamin, Lawrence N. P.; Walsh, Dominic M.; Selkoe, Dennis J.; Young-Pearse, Tracy L.

    2014-01-01

    Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by extracellular plaques containing amyloid β (Aβ)-protein and intracellular tangles containing hyperphosphorylated Tau protein. Here, we describe the generation of inducible pluripotent stem cell lines from patients harboring the London familial AD (fAD) amyloid precursor protein (APP) mutation (V717I). We examine AD-relevant phenotypes following directed differentiation to forebrain neuronal fates vulnerable in AD. We observe that over differentiation time to mature neuronal fates, APP expression and levels of Aβ increase dramatically. In both immature and mature neuronal fates, the APPV717I mutation affects both β- and γ-secretase cleavage of APP. Although the mutation lies near the γ-secretase cleavage site in the transmembrane domain of APP, we find that β-secretase cleavage of APP is elevated leading to generation of increased levels of both APPsβ and Aβ. Furthermore, we find that this mutation alters the initial cleavage site of γ-secretase, resulting in an increased generation of both Aβ42 and Aβ38. In addition to altered APP processing, an increase in levels of total and phosphorylated Tau is observed in neurons with the APPV717I mutation. We show that treatment with Aβ-specific antibodies early in culture reverses the phenotype of increased total Tau levels, implicating altered Aβ production in fAD neurons in this phenotype. These studies use human neurons to reveal previously unrecognized effects of the most common fAD APP mutation and provide a model system for testing therapeutic strategies in the cell types most relevant to disease processes. PMID:24524897

  7. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study

    PubMed Central

    Kaspar, Felix; Jelinek, Herbert F.; Perkins, Steven; Al-Aubaidy, Hayder A.; deJong, Bev; Butkowski, Eugene

    2016-01-01

    Objective. This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Design. Cohort study with repeated-measures design. Methods. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. Results. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (−20%; p = 0.047) and a decrease of MCP-1 (−17.9%; p = 0.03). Conclusion. This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis. PMID:27212809

  8. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline.

    PubMed

    Jonsson, Thorlakur; Atwal, Jasvinder K; Steinberg, Stacy; Snaedal, Jon; Jonsson, Palmi V; Bjornsson, Sigurbjorn; Stefansson, Hreinn; Sulem, Patrick; Gudbjartsson, Daniel; Maloney, Janice; Hoyte, Kwame; Gustafson, Amy; Liu, Yichin; Lu, Yanmei; Bhangale, Tushar; Graham, Robert R; Huttenlocher, Johanna; Bjornsdottir, Gyda; Andreassen, Ole A; Jönsson, Erik G; Palotie, Aarno; Behrens, Timothy W; Magnusson, Olafur T; Kong, Augustine; Thorsteinsdottir, Unnur; Watts, Ryan J; Stefansson, Kari

    2012-08-01

    The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.

  9. Better Lung Cancer Survival? There's an App for That

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159289.html Better Lung Cancer Survival? There's an App for That Study ... HealthDay News) -- A new smartphone app may help lung cancer patients live longer and better by monitoring ...

  10. ROLE OF THE MATERNAL ACUTE PHASE RESPONSE AND TUMOR NECROSIS FACTOR ALPHA IN THE DEVELOPMENTAL TOXICITY OF LIPOPOLYSACCHARIDE IN THE CD-1 MOUSE

    EPA Science Inventory

    ABSTRACT
    The acute phase response (APR) functions to reset metabolic homeostasis following infectious, toxic or traumatic insult. TNF- , a putative mediator of the APR, has been associated with fetal death in rodents and preterm labor and delivery in humans. We hypothesized...

  11. 77 FR 12796 - Commerce Business Apps Challenge

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... Office of the Secretary Commerce Business Apps Challenge AGENCY: Office of the Secretary (OS), Department... help U.S. businesses grow and create jobs. Recently, the White House launched the BusinessUSA Initiative ( www.Business.USA.gov ) to help further these goals. This notice announces the Commerce...

  12. North Tyneside Perspective on Primary Science APP

    ERIC Educational Resources Information Center

    Keilty, Ged

    2010-01-01

    The status of primary science as a core subject has been gradually corroded in recent years, with the abolition of targets for science and the focus of the primary national strategy on literacy and numeracy. The NAIGS Committee were very well positioned within local authorities to pilot APP, but first had to write the criteria. Towards the end of…

  13. Ebola - What You Need to Know app.

    PubMed

    Evans, Roger

    2015-02-01

    This app is the pocket companion to the Ebola in Africa section of the International SOS website. With headquarters in London and Singapore, International SOS is a company that provides medical, clinical and security services in 81 countries for organisations with international operations. PMID:25627521

  14. Athletic Training Education: There's an App for That

    ERIC Educational Resources Information Center

    Keeley, Kim; Potteiger, Kelly; Brown, Christopher D.

    2015-01-01

    Context: Mobile applications (apps) are growing in popularity due to the increased use of smartphones. Many available apps are educational in nature and may provide both students and educators freedom for learning to occur outside of the typical classroom environment. Objective: To provide a description of relevant apps along with a brief synopsis…

  15. Using the Modern Technology That Is the "App"

    ERIC Educational Resources Information Center

    Bernardelli, Alessio

    2013-01-01

    A few years ago, the sight of the letters APP would have made teachers in England think of the Assessing Pupils' Progress assessment approach introduced by the government. Now, when they see those same letters they mostly think about smartphone and tablet applications, shortened to "apps." With the thousands of apps available in the…

  16. Cleaning up That Mess: A Framework for Classifying Educational Apps

    ERIC Educational Resources Information Center

    Cherner, Todd; Dix , Judy; Lee, Corey

    2014-01-01

    As tablet technologies continue to evolve, the emergence of educational applications (apps) is impacting the work of teacher educators. Beyond online lists of best apps for education and recommendations from colleagues, teacher educators have few resources available to support their teaching of how to select educational apps. In response, this…

  17. English Language Teaching Apps: Positioning Parents and Young Learners

    ERIC Educational Resources Information Center

    Chik, Alice

    2014-01-01

    Since the introduction of iPads in 2010, the sales of tablet computers and mobile applications (apps) have grown exponentially. iPads and other tablets are marketed as learning tools, and many apps target learners as young as six months old. This article reports on a research project examining the unique features of English learning apps based on…

  18. Educational Behavior Apps and Wearable Devices: Current Research and Prospects

    ERIC Educational Resources Information Center

    Lowe, Heather

    2016-01-01

    Dartmouth and MIT have developed educational behavior apps and wearable devices that collect contiguous streams of data from student users. Given the consent of the user, the app collects information about a student's physical activity, sleep patterns, and location to form conjectures about social and academic behavior. These apps have the…

  19. Using Apps to Support Disciplinary Literacy and Science Learning

    ERIC Educational Resources Information Center

    Castek, Jill; Beach, Richard

    2013-01-01

    Apps, specialized programs used on mobile computers, can be used in innovative ways to enhance science and literacy learning. With the skilled guidance of their teachers, students can exploit app affordances for learning and acquire disciplinary literacies unique to science. This article showcases apps that help students to access information,…

  20. The App Squad: SLJ's Advisors Weigh in on Kids' Book Apps

    ERIC Educational Resources Information Center

    Ishizuka, Kathy

    2011-01-01

    In this article, "School Library Journal's" ("SLJ") advisors talk about book apps for kids. They discuss what they like, what one should look for in discerning the best for kids and teens, and where this all might be headed.

  1. REM sleep deprivation of rats induces acute phase response in liver.

    PubMed

    Pandey, Atul Kumar; Kar, Santosh Kumar

    2011-07-01

    REM sleep is essential for maintenance of body physiology and its deprivation is fatal. We observed that the levels of ALT and AST enzymes and pro-inflammatory cytokines like IL-1 β, IL-6 and IL-12 circulating in the blood of REM sleep deprived rats increased in proportion to the extent of sleep loss. But in contrast the levels of IFN-γ and a ∼200 kDa protein, identified by N-terminal sequencing to be alpha-1-inhibitor-3(A1I3), decreased significantly. Quantitative PCR analysis confirmed that REM sleep deprivation down regulates AII3 gene and up regulates IL1 β, IL6 and their respective receptors gene expression in the liver initiating its inflammation.

  2. Endometrial gene expression of acute phase extracellular matrix components following estrogen disruption of pregnancy in pigs.

    PubMed

    Ashworth, Morgan D; Ross, Jason W; Stein, Daniel; White, Frank; Geisert, Rodney D

    2010-12-01

    In pigs, administration of estrogen to gilts on Days 9 and 10 of pregnancy causes conceptus fragmentation and death between Days 15 and 18 of gestation. Conceptus degeneration is associated with breakdown of the microvilli surface glycocalyx on the lumenal epithelium (LE). We previously identified endometrial expression of inter-α-trypsin inhibitor (ITI) and hyaluronic acid (HA), which are key components of extracellular matrix (ECM), during the period of conceptus attachment to the uterine surface in the pig. Tumor necrosis factor-α-inducible protein-6 (TNFAIP6) serves as a linker for ECM expansion and is stimulated by prostaglandin E (PGE). We hypothesized that early estrogen administration alters the normal ECM components forming glycocalyx on the LE. Bred gilts (4 gilts/trt/day) were treated with either 5mg estradiol cypionate (E) or corn oil (CO) on Days 9 and 10 of gestation. The uterus was surgically removed on either Days 10, 12, 13, 15 and 17 of gestation and endometrial tissue snap frozen in liquid nitrogen. Endometrial tumor necrosis factor-α (TNF), TNFAIP6, interleukin 6 (IL6), and inter-α-trypsin inhibitor heavy chains (ITIH) were detected during early pregnancy thereby indicating all components for maintenance of the extracellular glycocalyx are present in the endometrium of pigs. However, only gene expression of ITIH2 was suppressed by E-treatment. TNFAIP6 protein was detected across all days of gestation but was not affected by E-treatment. The present study demonstrates that while the pig endometrium expresses key components of ECM only ITIH2 gene expression was altered by E-treatment. A decrease in ITIH2 could lead to the possible loss of the uterine glycocalyx leading to conceptus degeneration; however, other factors may be involved with the loss of glycocalyx during implantation in the pig following E-treatment.

  3. An Over Expression APP Model for Anti-Alzheimer Disease Drug Screening Created by Zinc Finger Nuclease Technology

    PubMed Central

    Mao, Yiqing; Li, Zhixin; Wang, Rong; Guo, Tingting; Jin, Ling; Song, Rongjing; Xu, Wei; Zhou, Na; Zhang, Yizhuang; Hu, Ruobi; Wang, Xi; Huang, Huakang; Lei, Zhen; Niu, Gang; Irwin, David M.; Tan, Huanran

    2013-01-01

    Zinc Finger Nucleases (ZFNs), famous for their ability to precisely and efficiently modify specific genomic loci, have been employed in numerous transgenic model organism and cell constructions. Here we employ the ZFNs technology, with homologous recombination (HR), to construct sequence-specific Amyloid Precursor Protein (APP) knock-in cells. With the use of ZFNs, we established APP knock in cell lines with gene-modification efficiencies of about 7%. We electroporated DNA fragment containing the promoter and the protein coding regions of the zinc finger nucleases into cells, instead of the plasmids, to avoid problems associated with off target homologous recombination, and adopted a pair of mutated FokI cleavage domains to reduce the toxic effects of the ZFNs on cell growth. Since over-expression of APP, or a subdomain of it, might lead to an immediately lethal effect, we used the Cre-LoxP System to regulate APP expression. Our genetically transformed cell lines, w5c1 and s12c8, showed detectable APP and Amyloid β (Aβ) production. The Swedish double mutation in the APP coding sequence enhanced APP and Aβ abundance. What is more, the activity of the three key secretases in Aβ formation could be modulated, indicating that these transgenic cells have potential for drug screening to modify amyloid metabolism in cells. Our transformed cells could readily be propagated in culture and should provide an excellent experimental medium for elucidating aspects of the molecular pathogenesis of Alzheimer’s disease, especially those concerning the amyloidogenic pathways involving mutations in the APP coding sequence. The cellular models may also serve as a tool for deriving potentially useful therapeutic agents. PMID:24223114

  4. An over expression APP model for anti-Alzheimer disease drug screening created by zinc finger nuclease technology.

    PubMed

    Zhang, Xiaojing; Li, Hui; Mao, Yiqing; Li, Zhixin; Wang, Rong; Guo, Tingting; Jin, Ling; Song, Rongjing; Xu, Wei; Zhou, Na; Zhang, Yizhuang; Hu, Ruobi; Wang, Xi; Huang, Huakang; Lei, Zhen; Niu, Gang; Irwin, David M; Tan, Huanran

    2013-01-01

    Zinc Finger Nucleases (ZFNs), famous for their ability to precisely and efficiently modify specific genomic loci, have been employed in numerous transgenic model organism and cell constructions. Here we employ the ZFNs technology, with homologous recombination (HR), to construct sequence-specific Amyloid Precursor Protein (APP) knock-in cells. With the use of ZFNs, we established APP knock in cell lines with gene-modification efficiencies of about 7%. We electroporated DNA fragment containing the promoter and the protein coding regions of the zinc finger nucleases into cells, instead of the plasmids, to avoid problems associated with off target homologous recombination, and adopted a pair of mutated FokI cleavage domains to reduce the toxic effects of the ZFNs on cell growth. Since over-expression of APP, or a subdomain of it, might lead to an immediately lethal effect, we used the Cre-LoxP System to regulate APP expression. Our genetically transformed cell lines, w5c1 and s12c8, showed detectable APP and Amyloid β (Aβ) production. The Swedish double mutation in the APP coding sequence enhanced APP and Aβ abundance. What is more, the activity of the three key secretases in Aβ formation could be modulated, indicating that these transgenic cells have potential for drug screening to modify amyloid metabolism in cells. Our transformed cells could readily be propagated in culture and should provide an excellent experimental medium for elucidating aspects of the molecular pathogenesis of Alzheimer's disease, especially those concerning the amyloidogenic pathways involving mutations in the APP coding sequence. The cellular models may also serve as a tool for deriving potentially useful therapeutic agents.

  5. Octyl Gallate Markedly Promotes Anti-Amyloidogenic Processing of APP through Estrogen Receptor-Mediated ADAM10 Activation

    PubMed Central

    Zhang, She-Qing; Sawmiller, Darrell; Li, Song; Rezai-Zadeh, Kavon; Hou, Huayan; Zhou, Shufeng; Shytle, Douglas; Giunta, Brian; Fernandez, Frank; Mori, Takashi; Tan, Jun

    2013-01-01

    Our previous studies showed that the green tea-derived polyphenolic compound (−)-epigallocatechin-3 gallate (EGCG) reduces amyloid-β (Aβ) production in both neuronal and mouse Alzheimer’s disease (AD) models in concert with activation of estrogen receptor-α/phosphatidylinositide 3-kinase/protein kinase B (ERα/PI3K/Akt) signaling and anti-amyloidogenic amyloid precursor protein (APP) α-secretase (a disintegrin and metallopeptidase domain-10, ADAM10) processing. Since the gallate moiety in EGCG may correspond to the 7α position of estrogen, thereby facilitating ER binding, we extensively screened the effect of other gallate containing phenolic compounds on APP anti-amyloidogenic processing. Octyl gallate (OG; 10 µM), drastically decreased Aβ generation, in concert with increased APP α-proteolysis, in murine neuron-like cells transfected with human wild-type APP or “Swedish” mutant APP. OG markedly increased production of the neuroprotective amino-terminal APP cleavage product, soluble APP-α (sAPPα). In accord with our previous study, these cleavage events were associated with increased ADAM10 maturation and reduced by blockade of ERα/PI3k/Akt signaling. To validate these findings in vivo, we treated Aβ-overproducing Tg2576 mice with OG daily for one week by intracerebroventricular injection and found decreased Aβ levels associated with increased sAPPα. These data indicate that OG increases anti-amyloidogenic APP α-secretase processing by activation of ERα/PI3k/Akt signaling and ADAM10, suggesting that this compound may be an effective treatment for AD. PMID:23977176

  6. Smartphone Apps for Schizophrenia: A Systematic Review

    PubMed Central

    2015-01-01

    Background There is increasing interest in using mobile technologies such as smartphones for improving the care of patients with schizophrenia. However, less is known about the current clinical evidence for the feasibility and effectiveness of smartphone apps in this population. Objective To review the published literature of smartphone apps applied for the care of patients with schizophrenia and other psychotic disorders. Methods An electronic database search of Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, Allied and Complementary Medicine, Health and Psychosocial Instruments, PsycINFO, and Embase was conducted on May 24, 2015. All eligible studies were systematically reviewed, and proportional meta-analyses were applied to pooled data on recruitment, retention, and adherence to examine the overall feasibility of smartphone interventions for schizophrenia. Results Our search produced 226 results from which 7 eligible articles were identified, reporting on 5 studies of smartphone apps for patients with schizophrenia. All examined feasibility, and one assessed the preliminary efficacy of a smartphone intervention for schizophrenia. Study lengths varied between 6 and 130 days. Overall retention was 92% (95% CI 82-98%). Participants consistently used the smartphone apps on more than 85% of days during the study period, averaging 3.95 interactions per person per day. Furthermore, participants responded to 71.9% of automated prompts (95% CI 65.7-77.8%). Participants reported a range of potential benefits from the various interventions, and user experience was largely positive. Conclusions Although small, the current published literature demonstrates strong evidence for the feasibility of using smartphones to enhance the care of people with schizophrenia. High rates of engagement and satisfaction with a broad range of apps suggest the nascent potential of this mobile technology. However, there remains limited

  7. Genome-wide association study identifies two novel regions at 11p15.5-p13 and 1p31 with major impact on acute-phase serum amyloid A.

    PubMed

    Marzi, Carola; Albrecht, Eva; Hysi, Pirro G; Lagou, Vasiliki; Waldenberger, Melanie; Tönjes, Anke; Prokopenko, Inga; Heim, Katharina; Blackburn, Hannah; Ried, Janina S; Kleber, Marcus E; Mangino, Massimo; Thorand, Barbara; Peters, Annette; Hammond, Christopher J; Grallert, Harald; Boehm, Bernhard O; Kovacs, Peter; Geistlinger, Ludwig; Prokisch, Holger; Winkelmann, Bernhard R; Spector, Tim D; Wichmann, H-Erich; Stumvoll, Michael; Soranzo, Nicole; März, Winfried; Koenig, Wolfgang; Illig, Thomas; Gieger, Christian

    2010-11-01

    Elevated levels of acute-phase serum amyloid A (A-SAA) cause amyloidosis and are a risk factor for atherosclerosis and its clinical complications, type 2 diabetes, as well as various malignancies. To investigate the genetic basis of A-SAA levels, we conducted the first genome-wide association study on baseline A-SAA concentrations in three population-based studies (KORA, TwinsUK, Sorbs) and one prospective case cohort study (LURIC), including a total of 4,212 participants of European descent, and identified two novel genetic susceptibility regions at 11p15.5-p13 and 1p31. The region at 11p15.5-p13 (rs4150642; p = 3.20×10(-111)) contains serum amyloid A1 (SAA1) and the adjacent general transcription factor 2 H1 (GTF2H1), Hermansky-Pudlak Syndrome 5 (HPS5), lactate dehydrogenase A (LDHA), and lactate dehydrogenase C (LDHC). This region explains 10.84% of the total variation of A-SAA levels in our data, which makes up 18.37% of the total estimated heritability. The second region encloses the leptin receptor (LEPR) gene at 1p31 (rs12753193; p = 1.22×10(-11)) and has been found to be associated with CRP and fibrinogen in previous studies. Our findings demonstrate a key role of the 11p15.5-p13 region in the regulation of baseline A-SAA levels and provide confirmative evidence of the importance of the 1p31 region for inflammatory processes and the close interplay between A-SAA, leptin, and other acute-phase proteins. PMID:21124955

  8. Apps and eating disorders: A systematic clinical appraisal

    PubMed Central

    Rothwell, Emily R.

    2015-01-01

    ABSTRACT Objective Smartphone applications (apps) are proliferating and health‐related apps are particularly popular. The aim of this study was to identify, characterize, and evaluate the clinical utility of apps designed either for people with eating disorders or for eating disorder professionals. Method A search of the major app stores identified 805 potentially relevant apps, of which 39 were primarily designed for people with eating disorders and five for professionals. Results The apps for people with eating disorders had four main functions. Most common was the provision of advice, the quality of which ranged from sound to potentially harmful. Five apps included self‐assessment tools but only two used methods that would generally be viewed as reliable. Four apps had the self‐monitoring of eating habits as a major feature. Entering information into these apps could be accomplished with varying degrees of ease, but viewing it was more difficult. One app allowed the transfer of information between patients and clinicians. Discussion The enthusiasm for apps outstrips the evidence supporting their use. Given their popularity, it is suggested that clinicians evaluate app use as part of routine assessment. The clinical utility of the existing apps is not clear. Some are capable of tracking key features over time, but none has the functions required for analytic self‐monitoring as in cognitive behavioral treatments. The full potential of apps has yet to be realized. Specialized apps could be designed to augment various forms of treatment, and there is the possibility that they could deliver an entire personalized intervention. © 2015 The Authors. International Journal of Eating Disorders published by Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:1038–1046) PMID:25728705

  9. Experimental alveolitis in rats: microbiological, acute phase response and histometric characterization of delayed alveolar healing

    PubMed Central

    RODRIGUES, Moacyr Tadeu Vicente; CARDOSO, Camila Lopes; de CARVALHO, Paulo Sérgio Perri; CESTARI, Tânia Mary; FERES, Magda; GARLET, Gustavo Pompermaier; FERREIRA JÚNIOR, Osny

    2011-01-01

    The pathogenesis of alveolitis is not well known and therefore experimental situations that mimic some features of this disease should be developed. Objective In this study, the evolution of the experimentally induced infection in rat sockets is characterized, which leads to clinical signs of suppurative alveolitis with remarkable wound healing disturbs. Material and methods Non-infected (Group I) and experimentally infected sockets in Rattus novergicus (Group II) were histometrically evaluated regarding the kinetics of alveolar healing. In addition, the characterization of the present bacteria in inoculation material and the serum levels of C-reactive protein (CRP) were performed. The detected species were Capnocytophaga ochracea, Fusobacterium nucleatum ss nucleatum, Prevotella melaninogenica, Streptococcus anginosus, Treponema socranskii and Streptococcus sanguis. Results All experimentally infected rats developed suppurative alveolitis, showing higher levels of CRP in comparison to those non-infected ones. Furthermore, infected rats presented a significant delayed wound healing as measured by the histometric analysis (higher persistent polymorphonuclear infiltrate and lower density of newly formed bone). Conclusion These findings indicate that rat sockets with experimentally induced infection produced higher levels of serum CRP, showing the potential of disseminated infection and a disturb in the alveolar repair process in an interesting experimental model for alveolitis studies. PMID:21625744

  10. The correlation between ferritin level and acute phase parameters in rheumatoid arthritis and systemic lupus erythematosus

    PubMed Central

    Seyhan, Serkan; Pamuk, Ömer Nuri; Pamuk, Gülsüm Emel; Çakır, Necati

    2014-01-01

    Objective In this study, we evaluated the relationship between ferritin levels and disease activation in rheumatoid arthritis (RA) patients. Material and Methods We included 44 patients with RA, 20 patients with systemic lupus erythematosus (SLE), 25 patients with infection, 22 patients with malignancy, and 20 healthy control subjects. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), whole blood count, and serum iron parameters were determined in all cases. The joint findings in RA patients were recorded, and disease activity score (DAS) was calculated. In SLE patients, antinuclear antibody (ANA) and anti-dsDNA titers and C3 and C4 complement levels were determined. SLE disease activity index (SLEDAI) score was calculated. Results Serum ferritin levels in the RA, SLE, and control groups were lower than those in the infection and malignancy groups (p<0.05). The ferritin levels in the RA group did not differ significantly from the SLE and control groups. In RA patients, serum ferritin level had a positive correlation with ESR, CRP, RF, platelet count, and DAS score and had a negative correlation with hematocrit (all p values <0.05). In SLE patients, on the other hand, serum ferritin had a positive correlation with ANA, anti-dsDNA, and SLEDAI (all p values <0.05). According to DAS, ferritin level in inactive RA patients was lower than that in active RA patients. When transferrin saturation was considered, iron deficiency anemia was a quite frequent finding in both active and inactive RA patients. Conclusion Interestingly, we observed that ferritin level in RA patients was similar to the control group; however, it was a good parameter of disease activation. This is because a reduction in storage iron and resultant iron deficiency anemia are very common in RA patients.

  11. Purification and determination of C-reactive protein and inter-α-trypsin inhibitor heavy chain 4 in dogs after major surgery through generation of specific antibodies.

    PubMed

    Soler, L; García, N; Unzueta, A; Piñeiro, M; Álava, M A; Lampreave, F

    2016-10-15

    Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) and C-reactive protein (CRP) have been isolated from acute phase dog sera by affinity chromatography with insolubilized polyclonal antibodies anti pig Major Acute phase Protein (Pig-MAP) and with p-Aminophenyl Phosphoryl Choline, respectively. Isolated proteins were used to prepare specific polyclonal rabbit antisera that have allowed quantifying their concentration in serum samples by single radial immunodifussion. Both proteins were quantified in sera from female dogs that had undergone ovariohysterectomy (OVH, n=9) or mastectomy (n=10). The observed increases in CRP concentrations showed that surgical traumas induced an acute phase response of a great magnitude in the dogs. In both surgeries a four-fold increase of ITIH4 concentrations was detected. It can be concluded that ITIH4 is a new positive acute phase protein in dogs, as reported in other species.

  12. Purification and determination of C-reactive protein and inter-α-trypsin inhibitor heavy chain 4 in dogs after major surgery through generation of specific antibodies.

    PubMed

    Soler, L; García, N; Unzueta, A; Piñeiro, M; Álava, M A; Lampreave, F

    2016-10-15

    Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) and C-reactive protein (CRP) have been isolated from acute phase dog sera by affinity chromatography with insolubilized polyclonal antibodies anti pig Major Acute phase Protein (Pig-MAP) and with p-Aminophenyl Phosphoryl Choline, respectively. Isolated proteins were used to prepare specific polyclonal rabbit antisera that have allowed quantifying their concentration in serum samples by single radial immunodifussion. Both proteins were quantified in sera from female dogs that had undergone ovariohysterectomy (OVH, n=9) or mastectomy (n=10). The observed increases in CRP concentrations showed that surgical traumas induced an acute phase response of a great magnitude in the dogs. In both surgeries a four-fold increase of ITIH4 concentrations was detected. It can be concluded that ITIH4 is a new positive acute phase protein in dogs, as reported in other species. PMID:27590422

  13. Expression of B4GALNT1, an essential glycosyltransferase for the synthesis of complex gangliosides, suppresses BACE1 degradation and modulates APP processing

    PubMed Central

    Yamaguchi, Tokiaki; Yamauchi, Yoshio; Furukawa, Keiko; Ohmi, Yuhsuke; Ohkawa, Yuki; Zhang, Qing; Okajima, Tetsuya; Furukawa, Koichi

    2016-01-01

    Alzheimer’s disease (AD) is the most prevalent form of dementia characterized by the extracellular accumulation of amyloid β (Aβ) peptides, which are produced by proteolytic cleavages of amyloid precursor protein (APP). Gangliosides are involved in AD pathophysiology including Aβ deposition and APP processing, yet the detailed mechanisms are not fully understood. Here we examined how changes in the carbohydrate moiety of gangliosides alter APP processing in human melanoma cells, neuroectoderm-derived cells. We showed that forced expression of GD2, GM2 or GM1 (by introducing B4GALNT1 cDNA into cells not expressing this glycosyltransferase) results in increases of α- and β-site cleavages of APP with a prominent increase in β-cleavage. We also showed that β-site APP cleaving enzyme 1 (BACE1) protein is highly protected from the degradation in cells expressing these gangliosides, thereby increasing the expression of this protein. Unexpectedly, adding gangliosides exogenously altered neither BACE1 levels nor β-site cleavage. The stabilisation of BACE1 protein led to the increase of this protein in lipid rafts, where BACE1 processes APP. Based on the current results, we propose a hitherto undisclosed link between ganglioside expression and AD; the expression of B4GALNT1 positively regulates the β-site cleavage by mainly inhibiting the lysosomal degradation of BACE1 protein. PMID:27687691

  14. On the mechanism of activation of the BLUF domain of AppA.

    PubMed

    Laan, Wouter; Gauden, Magdalena; Yeremenko, Sergey; van Grondelle, Rienk; Kennis, John T M; Hellingwerf, Klaas J

    2006-01-10

    AppA, a transcriptional antirepressor, regulates the steady expression of photosynthesis genes in Rhodobacter sphaeroides in response to high-intensity blue light and to redox signals. Its blue-light sensing is mediated by an N-terminal BLUF domain, a member of a novel flavin fold. The photocycle of this domain (AppA(5-125)) includes formation of a slightly red-shifted long-lived signaling state, which is formed directly from the singlet excited state of the flavin on a subnanosecond time scale [Gauden et al. (2005) Biochemistry 44, 3653-3662]. The red shift of the absorption spectrum of this signaling state has been attributed to a rearrangement of its hydrogen-bonding interactions with the surrounding apoprotein. In this study we have characterized an AppA mutant with an altered aromatic amino acid: W104F. This mutant exhibits an increased lifetime of the singlet excited state of the flavin chromophore. Most strikingly, however, it shows a 1.5-fold increase in its quantum yield of signaling state formation. In addition, it shows a slightly increased rate of ground-state recovery. On top of this, the presence of imidazole, both in this mutant protein and in the wild-type BLUF domain, significantly accelerates the rate of ground-state recovery, suggesting that this rate is limited by rearrangement of (a) hydrogen bond(s). In total, an approximately 700-fold increase in recovery rate has been obtained, which makes the W104F BLUF domain of AppA, for example, suitable for future analyses with step-scan FTIR. The rate of ground-state recovery of the BLUF domain of AppA follows Arrhenius kinetics. This suggests that this domain itself does not undergo large structural changes upon illumination and that the structural transitions in full-length AppA are dominated by interdomain rearrangements.

  15. The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity

    PubMed Central

    Johnstone, Victoria P.A.; Shultz, Sandy R.; Yan, Edwin B.; O'Brien, Terence J.

    2014-01-01

    Abstract The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes. PMID:24927383

  16. Physiological and behavioral responses to an acute-phase response in zebra finches: immediate and short-term effects.

    PubMed

    Sköld-Chiriac, Sandra; Nord, Andreas; Nilsson, Jan-Åke; Hasselquist, Dennis

    2014-01-01

    Activation of the immune system to clear pathogens and mitigate infection is a costly process that might incur fitness costs. When vertebrates are exposed to pathogens, their first line of defense is the acute-phase response (APR), which consists of a suite of physiological and behavioral changes. The dynamics of the APR are relatively well investigated in mammals and domesticated birds but still rather unexplored in passerine birds. In this study, we injected male zebra finches (Taeniopygia guttata) with a bacterial endotoxin (lipopolysaccharide [LPS]) to assess the potential physiological, immunological, and behavioral responses during the time course of an APR and also to record any potential short-term effects by measuring the birds during the days after the expected APR. We found that LPS-injected zebra finches decreased activity and gained less body mass during the APR, compared to control individuals. In addition, LPS-injected birds increased their production of LPS-reactive antibodies and reduced their metabolic rate during the days after the expected APR. Our results show that zebra finches demonstrate sickness behaviors during an APR but also that physiological effects persist after the expected time course of an APR. These delayed effects might be either a natural part of the progression of an APR, which is probably true for the antibody response, or a short-term carryover effect, which is probably true for the metabolic response.

  17. Cytokine profile of a Holstein calf with bovine leukocyte adhesion deficiency during the acute-phase inflammatory response.

    PubMed

    Nagahata, Hajime; Hagiwara, Katsuro; Kasamatsu, Masahiko; Higuchi, Hidetoshi; Kurosawa, Takashi

    2002-12-01

    Changes in interleukin (IL)-1beta, IL-6 and IL-8 in serum, and their mRNA expression on neutrophils from a 4.6-month old Holstein young calf with bovine leukocyte adhesion deficiency (BLAD) during the acute phase were evaluated. IL-1beta concentrations in the serum of the calf with BLAD at age 143-162 days ranged from 8.7 to 16.6 ng/ml, whereas the values were less than 2.7 ng/ml in control calves. Serum IL-6 (0.04 ng/ml) was only detected on the 1st day when the animal was diagnosed with the BLAD. IL-1beta and IL-8 mRNA expression on neutrophils from the affected calf appeared to be similar to those of controls. Serum cytokine levels and their mRNA expression on neutrophils from the calf with BLAD appeared to be little affected by the deficient expression of beta(2)-integrin on leukocytes, and are considered to be modulated by the inflammatory stimuli. PMID:12520109

  18. Thrombin induces ischemic LTP (iLTP): implications for synaptic plasticity in the acute phase of ischemic stroke

    PubMed Central

    Stein, Efrat Shavit; Itsekson-Hayosh, Zeev; Aronovich, Anna; Reisner, Yair; Bushi, Doron; Pick, Chaim G.; Tanne, David; Chapman, Joab; Vlachos, Andreas; Maggio, Nicola

    2015-01-01

    Acute brain ischemia modifies synaptic plasticity by inducing ischemic long-term potentiation (iLTP) of synaptic transmission through the activation of N-Methyl-D-aspartate receptors (NMDAR). Thrombin, a blood coagulation factor, affects synaptic plasticity in an NMDAR dependent manner. Since its activity and concentration is increased in brain tissue upon acute stroke, we sought to clarify whether thrombin could mediate iLTP through the activation of its receptor Protease-Activated receptor 1 (PAR1). Extracellular recordings were obtained in CA1 region of hippocampal slices from C57BL/6 mice. In vitro ischemia was induced by acute (3 minutes) oxygen and glucose deprivation (OGD). A specific ex vivo enzymatic assay was employed to assess thrombin activity in hippocampal slices, while OGD-induced changes in prothrombin mRNA levels were assessed by (RT)qPCR. Upon OGD, thrombin activity increased in hippocampal slices. A robust potentiation of excitatory synaptic strength was detected, which occluded the ability to induce further LTP. Inhibition of either thrombin or its receptor PAR1 blocked iLTP and restored the physiological, stimulus induced LTP. Our study provides important insights on the early changes occurring at excitatory synapses after ischemia and indicates the thrombin/PAR1 pathway as a novel target for developing therapeutic strategies to restore synaptic function in the acute phase of ischemic stroke. PMID:25604482

  19. Clinical management apps: creating partnerships between providers and patients.

    PubMed

    Silow-Carroll, Sharon; Smith, Barbara

    2013-11-01

    The market for health applications, or apps, on mobile devices is growing rap­idly, with over 40,000 currently in use. One type of app technology--clinical manage­ment apps--enable patients and providers to work together to manage chronic conditions, particularly diabetes and asthma. These apps are mostly used by health plans and large health care organizations with an interest in improving outcomes and controlling costs. Challenges to broader adoption of apps include the lack of objective research to evalu­ate outcomes, uncertainty about how to pay for and encourage the use of cost-effective apps, and the absence of a regulatory framework that standardizes development to ensure performance. If this infrastructure is developed, apps may serve as a catalyst to stimulate the transformation of health care generally and target low-income populations to expand access to care and help reduce health disparities. PMID:24312989

  20. α(2A) adrenergic receptor promotes amyloidogenesis through disrupting APP-SorLA interaction.

    PubMed

    Chen, Yunjia; Peng, Yin; Che, Pulin; Gannon, Mary; Liu, Yin; Li, Ling; Bu, Guojun; van Groen, Thomas; Jiao, Kai; Wang, Qin

    2014-12-01

    Accumulation of amyloid β (Aβ) peptides in the brain is the key pathogenic factor driving Alzheimer's disease (AD). Endocytic sorting of amyloid precursor protein (APP) mediated by the vacuolar protein sorting (Vps10) family of receptors plays a decisive role in controlling the outcome of APP proteolytic processing and Aβ generation. Here we report for the first time to our knowledge that this process is regulated by a G protein-coupled receptor, the α(2A) adrenergic receptor (α(2A)AR). Genetic deficiency of the α(2A)AR significantly reduces, whereas stimulation of this receptor enhances, Aβ generation and AD-related pathology. Activation of α(2A)AR signaling disrupts APP interaction with a Vps10 family receptor, sorting-related receptor with A repeat (SorLA), in cells and in the mouse brain. As a consequence, activation of α(2A)AR reduces Golgi localization of APP and concurrently promotes APP distribution in endosomes and cleavage by β secretase. The α(2A)AR is a key component of the brain noradrenergic system. Profound noradrenergic dysfunction occurs consistently in patients at the early stages of AD. α(2A)AR-promoted Aβ generation provides a novel mechanism underlying the connection between noradrenergic dysfunction and AD. Our study also suggests α(2A)AR as a previously unappreciated therapeutic target for AD. Significantly, pharmacological blockade of the α(2A)AR by a clinically used antagonist reduces AD-related pathology and ameliorates cognitive deficits in an AD transgenic model, suggesting that repurposing clinical α(2A)R antagonists would be an effective therapeutic strategy for AD.

  1. Lamotrigine attenuates deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PS1 transgenic mice.

    PubMed

    Zhang, Mao-Ying; Zheng, Chuan-Yi; Zou, Ming-Ming; Zhu, Jian-Wei; Zhang, Yan; Wang, Jing; Liu, Chun-Feng; Li, Qi-Fa; Xiao, Zhi-Cheng; Li, Shao; Ma, Quan-Hong; Xu, Ru-Xiang

    2014-12-01

    Hyperactivity and its compensatory mechanisms may causally contribute to synaptic and cognitive deficits in Alzheimer's disease (AD). Blocking the overexcitation of the neural network, with levetiracetam (LEV), a sodium channel blocker applied in the treatment of epilepsy, prevented synaptic and cognitive deficits in human amyloid precursor protein (APP) transgenic mice. This study has brought the potential use of antiepileptic drugs (AEDs) in AD therapy. We showed that the chronic treatment with lamotrigine (LTG), a broad-spectrum AED, suppressed abnormal spike activity, prevented the loss of spines, synaptophysin immunoreactivity, and neurons, and thus attenuated the deficits in synaptic plasticity and learning and memory in APP and presenilin 1 (PS1) mice, which express human mutant APP and PS1. In contrast with LEV, which failed to reduce the generation of amyloid β, the chronic LTG treatment reduced the cleavage of APP by β-secretase and thus the numbers and the size of amyloid plaques in the brains of APP and PS1 mice. Moreover, the levels of brain-derived neurotrophic growth factor (BDNF) and nerve growth factor (NGF) were enhanced in the brains of APP and PS1 mice by the chronic LTG treatment. Therefore, these observations demonstrate that LTG attenuates AD pathology through multiple mechanisms, including modulation of abnormal network activity, reduction of the generation of amyloid beta and upregulation of BDNF and NGF. PMID:25044076

  2. TRPC6 specifically interacts with APP to inhibit its cleavage by γ-secretase and reduce Aβ production

    PubMed Central

    Wang, Junfeng; Lu, Rui; Yang, Jian; Li, Hongyu; He, Zhuohao; Jing, Naihe; Wang, Xiaomin; Wang, Yizheng

    2015-01-01

    Generation of β-amyloid (Aβ) peptide in Alzheimer's disease involves cleavage of amyloid precursor protein (APP) by γ-secretase, a protease known to cleave several substrates, including Notch. Finding specific modulators for γ-secretase could be a potential avenue to treat the disease. Here, we report that transient receptor potential canonical (TRPC) 6 specifically interacts with APP leading to inhibition of its cleavage by γ-secretase and reduction in Aβ production. TRPC6 interacts with APP (C99), but not with Notch, and prevents C99 interaction with presenilin 1 (PS1). A fusion peptide derived from TRPC6 also reduces Aβ levels without effect on Notch cleavage. Crossing APP/PS1 mice with TRPC6 transgenic mice leads to a marked reduction in both plaque load and Aβ levels, and improvement in structural and behavioural impairment. Thus, TRPC6 specifically modulates γ-secretase cleavage of APP and preventing APP (C99) interaction with PS1 via TRPC6 could be a novel strategy to reduce Aβ formation. PMID:26581893

  3. Nature apps: Waiting for the revolution.

    PubMed

    Jepson, Paul; Ladle, Richard J

    2015-12-01

    Apps are small task-orientated programs with the potential to integrate the computational and sensing capacities of smartphones with the power of cloud computing, social networking, and crowdsourcing. They have the potential to transform how humans interact with nature, cause a step change in the quantity and resolution of biodiversity data, democratize access to environmental knowledge, and reinvigorate ways of enjoying nature. To assess the extent to which this potential is being exploited in relation to nature, we conducted an automated search of the Google Play Store using 96 nature-related terms. This returned data on ~36 304 apps, of which ~6301 were nature-themed. We found that few of these fully exploit the full range of capabilities inherent in the technology and/or have successfully captured the public imagination. Such breakthroughs will only be achieved by increasing the frequency and quality of collaboration between environmental scientists, information engineers, computer scientists, and interested publics. PMID:26458392

  4. Caspr interaction with Amyloid Precursor Protein reduces amyloid-β generation in vitro.

    PubMed

    Fan, Liang-feng; Xu, De-en; Wang, Wei-hua; Yan, Ke; Wu, Hao; Yao, Xue-qin; Xu, Ru-xiang; Liu, Chun-feng; Ma, Quan-hong

    2013-08-26

    Contactin associated protein (Caspr), an adhesion molecule, plays roles in formation of paranodal junctions in myelinated axons, neurite outgrowth, synaptic plasticity in nervous system. Here we have shown a novel function of Caspr in pathogenesis of Alzheimer's disease (AD). Caspr distributes around amyloid plaques in APP/PS1 mice. Levels of Caspr increase in the cerebral cortex of 7-month-old APP/PS1 mice comparing to wild-type littermates. Caspr decreased protein levels of APP in both HEK-293 cells stably transfected with Indiana mutant APP (V717F; HEK-APP) and CHO cells which express endogenous APP, while it did not alter mRNA levels of APP. Furthermore, Caspr co-localizes and interacts with APP. Amyloid-β (Aβ) 40 and Aβ42 generation were also reduced in HEK-APP cells by Caspr overexpression. PMID:23748076

  5. Audio App Brings a Better Nights Sleep

    NASA Technical Reports Server (NTRS)

    2015-01-01

    Neuroscientist Seth Horowitz was part of a NASA-funded team at State University of New York Stony Brook demonstrating that low-amplitude vestibular stimulation could induce sleep. After recognizing the same stimulation could be applied through sound, Horowitz founded Sleep Genius, located in Park City, Utah, and released a mobile app of the same name that helps people to get a more restful sleep.

  6. Medical apps: public and academic perspectives.

    PubMed

    Krieger, William H

    2013-01-01

    Medical apps have featured in popular websites and mainstream news media in recent months. However, there has been almost no mention of these tools in journals focusing on relevant ethical or social issues, including conflict of interest, the role of politics in science, and technological oversight. This essay examines the role that these philosophical issues might play in answering both public and academic questions about these pieces of emergent technology.

  7. Interrater Reliability of mHealth App Rating Measures: Analysis of Top Depression and Smoking Cessation Apps

    PubMed Central

    Chan, Steven; Raynor, Geoffrey Stephen; Shwarts, Erik; Shanahan, Meghan; Landman, Adam B

    2016-01-01

    Background There are over 165,000 mHealth apps currently available to patients, but few have undergone an external quality review. Furthermore, no standardized review method exists, and little has been done to examine the consistency of the evaluation systems themselves. Objective We sought to determine which measures for evaluating the quality of mHealth apps have the greatest interrater reliability. Methods We identified 22 measures for evaluating the quality of apps from the literature. A panel of 6 reviewers reviewed the top 10 depression apps and 10 smoking cessation apps from the Apple iTunes App Store on these measures. Krippendorff’s alpha was calculated for each of the measures and reported by app category and in aggregate. Results The measure for interactiveness and feedback was found to have the greatest overall interrater reliability (alpha=.69). Presence of password protection (alpha=.65), whether the app was uploaded by a health care agency (alpha=.63), the number of consumer ratings (alpha=.59), and several other measures had moderate interrater reliability (alphas>.5). There was the least agreement over whether apps had errors or performance issues (alpha=.15), stated advertising policies (alpha=.16), and were easy to use (alpha=.18). There were substantial differences in the interrater reliabilities of a number of measures when they were applied to depression versus smoking apps. Conclusions We found wide variation in the interrater reliability of measures used to evaluate apps, and some measures are more robust across categories of apps than others. The measures with the highest degree of interrater reliability tended to be those that involved the least rater discretion. Clinical quality measures such as effectiveness, ease of use, and performance had relatively poor interrater reliability. Subsequent research is needed to determine consistent means for evaluating the performance of apps. Patients and clinicians should consider conducting their

  8. An interactive app for color deficient viewers

    NASA Astrophysics Data System (ADS)

    Lau, Cheryl; Perdu, Nicolas; Rodríguez-Pardo, Carlos E.; Süsstrunk, Sabine; Sharma, Gaurav

    2015-01-01

    Color deficient individuals have trouble seeing color contrasts that could be very apparent to individuals with normal color vision. For example, for some color deficient individuals, red and green apples do not have the striking contrast they have for those with normal color vision, or the abundance of red cherries in a tree is not immediately clear due to a lack of perceived contrast. We present a smartphone app that enables color deficient users to visualize such problematic color contrasts in order to help them with daily tasks. The user interacts with the app through the touchscreen. As the user traces a path around the touchscreen, the colors in the image change continuously via a transform that enhances contrasts that are weak or imperceptible for the user under native viewing conditions. Specifically, we propose a transform that shears the data along lines parallel to the dimension corresponding to the affected cone sensitivity of the user. The amount and direction of shear are controlled by the user's finger movement over the touchscreen allowing them to visualize these contrasts. Using the GPU, this simple transformation, consisting of a linear shear and translation, is performed efficiently on each pixel and in real-time with the changing position of the user's finger. The user can use the app to aid daily tasks such as distinguishing between red and green apples or picking out ripe bananas.

  9. Insights into the physiological function of the β-amyloid precursor protein: beyond Alzheimer's disease

    PubMed Central

    Dawkins, Edgar; Small, David H

    2014-01-01

    The β-amyloid precursor protein (APP) has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ) of Alzheimer's disease. However, the normal function of APP remains largely unknown. This article reviews studies on the structure, expression and post-translational processing of APP, as well as studies on the effects of APP in vitro and in vivo. We conclude that the published data provide strong evidence that APP has a trophic function. APP is likely to be involved in neural stem cell development, neuronal survival, neurite outgrowth and neurorepair. However, the mechanisms by which APP exerts its actions remain to be elucidated. The available evidence suggests that APP interacts both intracellularly and extracellularly to regulate various signal transduction mechanisms. This article reviews studies on the structure, expression and post-translational processing of β-amyloid precursor protein (APP), as well as studies on the effects of APP in vitro and in vivo. We conclude that the published data provide strong evidence that APP has a trophic function. APP is likely to be involved in neural stem cell development, neuronal survival, neurite outgrowth and neurorepair. However, the mechanisms by which APP exerts its actions remain to be elucidated. The available evidence suggests that APP interacts both intracellularly and extracellularly to regulate various signal transduction mechanisms. PMID:24517464

  10. Age determines the effects of blood pressure lowering during the acute phase of ischemic stroke: the TICA study.

    PubMed

    Leira, Rogelio; Millán, Mónica; Díez-Tejedor, Exuperio; Blanco, Miguel; Serena, Joaquín; Fuentes, Blanca; Rodríguez-Yáñez, Manuel; Castellanos, Mar; Lago, Aida; Dávalos, Antonio; Castillo, José

    2009-10-01

    To increase understanding of the influence of blood pressure (BP) changes on functional outcome, we designed a multicenter, prospective, observational study involving patients with ischemic stroke. We included 1092 patients with ischemic stroke. BP was measured on admission and after 8, 16, 24, 32, 40, and 48 hours, and the averages of the readings were taken every 8 hours on days 3 to 7, at the day of discharge, and at 3 months. The main study variable was modified Rankin scale at 3 months. Systolic BPs >181 mm Hg at the emergency department and after 24 hours were associated with poor prognosis (odds ratio [OR]: 2.2, 95% CI: 1.2 to 4.2 and OR: 1.3, 95% CI: 1.1 to 2.3, respectively); systolic BP <136 mm Hg at the emergency department also determined worse prognosis at 3 months (OR: 1.3; 95% CI: 1.1 to 2.9). The influence of systolic BP changes in the first hours depended on patient age. In elder patients (>70 years), reductions in systolic BP determined a significant increase in the proportion of patients with worse prognosis. In patients >80 years of age, decreases in systolic BP >27.2 mm Hg determined a worse prognosis in patients with antihypertensive treatment at the emergency department (n=91) compared with those who did not receive treatment (n=106; OR: 21.7, 95% CI: 13.6 to 33.5 versus OR: 8.5, 95% CI: 3.2 to 19.6). In summary, the effect of BP modification during the acute phase of ischemic stroke on functional outcome is strongly dependent on age.

  11. Serum levels of thrombomodulin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in the acute phase of Plasmodium vivax malaria.

    PubMed

    Ohnishi, K

    1999-02-01

    Elevated plasma or serum levels of thrombomodulin (TM), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin have been reported in several diseases. However, plasma or serum levels of TM, ICAM-1, VCAM-1, and E-selectin have not been investigated in the acute phase of Plasmodium vivax malaria. Serum TM, ICAM-1, VCAM-1, E-selectin, and creatinine levels were determined in six Japanese patients in the acute phase of vivax malaria and in seven healthy Japanese controls. Parasitemias of the peripheral blood were < 0.1% in five patients and 0.8% in one patient. The patients' mean +/- SD serum levels of TM, ICAM-1, VCAM-1, and E-selectin were 5.7 +/- 1.3 Fujirebio units/ml, 709 +/- 397 ng/ml, 2,112 +/- 782 ng/ml, and 99 +/- 28 ng/ml, respectively, and all were significantly greater than those in the controls (TM; P < 0.005, ICAM-1; P < 0.025, VCAM-1; P < 0.005, E-selectin; P < 0.025). However, no significant difference was identified between patients and controls for serum creatinine values. The serum levels of TM and VCAM-1 were not related to parasitemia. The elevation of serum TM levels suggests that endothelial cell damage occurs in the acute phase of vivax malaria.

  12. Apps Seeking Theories: Results of a Study on the Use of Health Behavior Change Theories in Cancer Survivorship Mobile Apps

    PubMed Central

    Fair, Kayla; Hong, Y Alicia; Beaudoin, Christopher E; Pulczinski, Jairus; Ory, Marcia G

    2015-01-01

    Background Thousands of mobile health apps are now available for use on mobile phones for a variety of uses and conditions, including cancer survivorship. Many of these apps appear to deliver health behavior interventions but may fail to consider design considerations based in human computer interface and health behavior change theories. Objective This study is designed to assess the presence of and manner in which health behavior change and health communication theories are applied in mobile phone cancer survivorship apps. Methods The research team selected a set of criteria-based health apps for mobile phones and assessed each app using qualitative coding methods to assess the application of health behavior change and communication theories. Each app was assessed using a coding derived from the taxonomy of 26 health behavior change techniques by Abraham and Michie with a few important changes based on the characteristics of mHealth apps that are specific to information processing and human computer interaction such as control theory and feedback systems. Results A total of 68 mobile phone apps and games built on the iOS and Android platforms were coded, with 65 being unique. Using a Cohen’s kappa analysis statistic, the inter-rater reliability for the iOS apps was 86.1 (P<.001) and for the Android apps, 77.4 (P<.001). For the most part, the scores for inclusion of theory-based health behavior change characteristics in the iOS platform cancer survivorship apps were consistently higher than those of the Android platform apps. For personalization and tailoring, 67% of the iOS apps (24/36) had these elements as compared to 38% of the Android apps (12/32). In the area of prompting for intention formation, 67% of the iOS apps (34/36) indicated these elements as compared to 16% (5/32) of the Android apps. Conclusions Mobile apps are rapidly emerging as a way to deliver health behavior change interventions that can be tailored or personalized for individuals. As these

  13. Neuropathology of the recessive A673V APP mutation: Alzheimer disease with distinctive features.

    PubMed

    Giaccone, Giorgio; Morbin, Michela; Moda, Fabio; Botta, Mario; Mazzoleni, Giulia; Uggetti, Andrea; Catania, Marcella; Moro, Maria Luisa; Redaelli, Veronica; Spagnoli, Alberto; Rossi, Roberta Simona; Salmona, Mario; Di Fede, Giuseppe; Tagliavini, Fabrizio

    2010-12-01

    Mutations of three different genes, encoding β-amyloid precursor protein (APP), presenilin 1 and presenilin 2 are associated with familial Alzheimer's disease (AD). Recently, the APP mutation A673V has been identified that stands out from all the genetic defects previously reported in these three genes, since it causes the disease only in the homozygous state (Di Fede et al. in Science 323:1473-1477, 2009). We here provide the detailed neuropathological picture of the proband of this family, who was homozygous for the APP A673V mutation and recently came to death. The brain has been studied by histological and immunohistochemical techniques, at the optical and ultrastructural levels. Cerebral Aβ accumulation and tau pathology were severe and extensive. Peculiar features were the configuration of the Aβ deposits that were of large size, mostly perivascular and exhibited a close correspondence between the pattern elicited by amyloid stainings and the labeling obtained with immunoreagents specific for Aβ40 or Aβ42. Moreover, Aβ deposition spared the neostriatum while deeply affecting the cerebellum, and therefore was not in compliance with the hierarchical topographical sequence of involvement documented in sporadic AD. Therefore, the neuropathological picture of familial AD caused by the APP recessive mutation A673V presents distinctive characteristics compared to sporadic AD or familial AD inherited as a dominant trait. Main peculiar features are the morphology, structural properties and composition of the Aβ deposits as well as their topographic distribution in the brain.

  14. Enhanced penetration of exogenous EPCs into brains of APP/PS1 transgenic mice

    PubMed Central

    Yuan, Xiaoyang; Mei, Bin; Zhang, Le; Zhang, Cuntai; Zheng, Miao; Liang, Huifang; Wang, Wei; Zheng, Jie; Ding, Ling; Zheng, Kai

    2016-01-01

    The aim of this study was to investigate the repair function of exogenous Endothelial progenitor cells (EPCs) for brain microvascular damage of the APP/PS1 transgenic mouse model of Alzheimer’s disease (AD). This study used a density-gradient centrifugation method to isolate mononuclear cells (MNCs) from mouse bone marrow, which were subsequently seeded and cultured. Cells were characterized by morphology and detection of the surface markers CD34 and CD133 at different time points by immunofluorescence (IF) and flow cytometry (FCM). Then, EPCs were transfected with GFP adenoviral vectors (GFP-EPCs). Wild-type (WT) and APP/PS1 transgenic mice both received GFP-EPCs injection through the tail vein, and using a PBS buffer injection as the control. Seven days later, the animals’ brain tissue was isolated. Expression of GFP was detected by quantitative polymerase chain reaction (qPCR) and western-blot (WB), while the fluorescence of GFP within the brains of mice was observed under a fluorescence microscope. Higher mRNA and protein expression of GFP, accompanied with increased green fluorescence, were detected in the brain of GFP-EPCs-injected APP/PS1 mice, as compared with GFP-EPCs-injected WT mice. The results show that the APP/PS1 transgenic mouse model of AD exhibited enhanced penetration of exogenous EPCs into brains than the WT mice. PMID:27186272

  15. Safflower yellow ameliorates cognition deficits and reduces tau phosphorylation in APP/PS1 transgenic mice.

    PubMed

    Ruan, Ying-Ying; Zhai, Wei; Shi, Xiao-Meng; Zhang, Lu; Hu, Yan-Li

    2016-10-01

    Alzheimer's disease (AD), the most common cause of dementia worldwide, is mainly characterized by the aggregated β-amyloid (Aβ) and hyperphosphorylated tau. Safflower yellow (SY) is a novel water extract of natural safflower and has been suggested to ameliorate memory deficits in several animal models of dementia. In this study, we aimed to investigate the effect and mechanism of SY on deficits of learning and memory and hyperphosphorylation of tau in APP/PS1 double transgenic mice. APP/PS1 mice were administered with SY (10, 30, 100 mg/kg) by oral gavage for three months at the age of six months. The ability of learning and memory was investigated using the step-down test and Morris water maze test, and protein level in the brain was evaluated using western blot. Here, we found that SY treatment can improve spatial learning and memory ability, and reduce tau hyperphosphorylation at Ser199, Thr205, Ser396, Ser404 sites in APP/PS1 mice. In addition, the activity the of cyclin-dependent kinase 5 (CDK-5) and glycogen synthase kinase 3β (GSK-3β), major kinases involved in tau phosphorylation, was siginificantly decreased in APP/PS1 mice by SY treatment. These results support SY can serve as a promising multitarget neuronal therapeutic agent for the treatment of AD.

  16. Safflower yellow ameliorates cognition deficits and reduces tau phosphorylation in APP/PS1 transgenic mice.

    PubMed

    Ruan, Ying-Ying; Zhai, Wei; Shi, Xiao-Meng; Zhang, Lu; Hu, Yan-Li

    2016-10-01

    Alzheimer's disease (AD), the most common cause of dementia worldwide, is mainly characterized by the aggregated β-amyloid (Aβ) and hyperphosphorylated tau. Safflower yellow (SY) is a novel water extract of natural safflower and has been suggested to ameliorate memory deficits in several animal models of dementia. In this study, we aimed to investigate the effect and mechanism of SY on deficits of learning and memory and hyperphosphorylation of tau in APP/PS1 double transgenic mice. APP/PS1 mice were administered with SY (10, 30, 100 mg/kg) by oral gavage for three months at the age of six months. The ability of learning and memory was investigated using the step-down test and Morris water maze test, and protein level in the brain was evaluated using western blot. Here, we found that SY treatment can improve spatial learning and memory ability, and reduce tau hyperphosphorylation at Ser199, Thr205, Ser396, Ser404 sites in APP/PS1 mice. In addition, the activity the of cyclin-dependent kinase 5 (CDK-5) and glycogen synthase kinase 3β (GSK-3β), major kinases involved in tau phosphorylation, was siginificantly decreased in APP/PS1 mice by SY treatment. These results support SY can serve as a promising multitarget neuronal therapeutic agent for the treatment of AD. PMID:27311611

  17. Appy Hour: Health Sciences Professionals Learn About Apps.

    PubMed

    Casucci, Tallie; Gregory, Joan M; Shipman, Jean P

    2016-01-01

    Appy Hour is a recurring event hosted by an academic health sciences library featuring apps that are informally presented and demonstrated by invited speakers. The audience is encouraged to ask questions during the presentation of the featured app(s). This event provides learning and networking opportunities for health sciences faculty, staff, students, and health care professionals. This article illustrates the process for hosting the event, shares lessons learned, and discusses possible future directions to gain a wider audience. PMID:27391175

  18. [Complex network analysis on dynamic change regularity of combining use of Chinese and western medicine in 27,678 cases with ischemic stroke in acute phase].

    PubMed

    Yang, Wei; Li, Yang; Sun, Lei-lei; Xie, Yan-ming; Guo, Chong-hui; Zhuang, Yan

    2015-12-01

    The acute phase of ischemic stroke patients are often treated with both Chinese patent medicine:and western medicine therapies in clinical practice. This research included 27,678 cases of the acute phase of ischemic stroke came from 14 3A level hospitals. We collected data from patients with ischemic stroke who used both Chinese patent medicine and western medicine and were hopitalized within 14 days from hospital information system (HIS). Constructing complex network of Chinese patent medicine and western medicine were found to show scale-free network. Hierarchical structure of the core algorithm was used to analyze the characteristics of combined core Chinese patent medicine and western medicine in admission condition of "acute", "critically", and "general" of ischemic stroke acute phase patient within one day, 2-3 days, 4-7 days and 8-14 days. We found that the core Chinese patent medicine mainly used for activate blood and resolve stasis medicine, and phlegm eliminating brain refreshing medicine in all kinds of patients, but the phlegm eliminating brain refreshing medicine were used to reduce with time elapsing. The core western medicine mainly used for anti-platelet medicine, improve circulation medicine, neuroprotective medicine, anticoagulants medicine and dehydration medicine. The dehydration medicine as the core western medicine for critically patients within 14 days, but the patients for general admission as core western medicine within 3 days. The neuroprotective medicine was used to decreases after 7 days in hospital. Combination of Chinese patent medicine and western medicine were mainly for neuroprotective medicine + activate blood and resolve stasis medicine, and anti-platelet medicine + activate blood and resolve stasis medicine, and improve circulation medicine + activate blood and resolve stasis medicine. The phlegm eliminating brain refreshing medicine was mainly combined with neuroprotective medicine by urgent and general admission condition

  19. mHealth Apps and Their Risks - Taking Stock.

    PubMed

    Albrecht, Urs-Vito; von Jan, Ute

    2016-01-01

    Despite the popularity of health related apps and the great potential they hold for improving health care, the risks as well as potential hazards posed by such apps are often not adequately appreciated by users. Based on an analysis of scientific literature as well as anecdotal evidence, this contribution addresses the most common risks and pitfalls of health related apps (e.g. related to physical integrity as well as bodily and mental wellbeing) that users may encounter and sketches some remedies. While certainly not exhaustive, the mentioned aspects may serve as a starting point to raise awareness about potential risks of health related apps. PMID:27350511

  20. smartApps Package v 4.8

    SciTech Connect

    Anderson, Robert

    2009-12-04

    The smartApps package provides high-speed communication links between multiple Umbra sessions and/or SMART sessions. Modules within Packages/smartApps: Packages/smartApps/smartBlackboard: The original Broadcast module connected Umbra connectors to the SMART (Sandia's Modular Architecture for Robotics and Teleoperation) blackboard using UDP and TCP connections. Connectors are added to the module for each connection. Originally written by Scott Gladwell and maintained and updated by Robert J. Anderson. Packages/smartApps/smartBroadcast: A highly efficient version of packet based communication for connecting distributed SMART and Umbra systems together using UDP broadcasts.

  1. smartApps Package v 4.8

    2009-12-04

    The smartApps package provides high-speed communication links between multiple Umbra sessions and/or SMART sessions. Modules within Packages/smartApps: Packages/smartApps/smartBlackboard: The original Broadcast module connected Umbra connectors to the SMART (Sandia's Modular Architecture for Robotics and Teleoperation) blackboard using UDP and TCP connections. Connectors are added to the module for each connection. Originally written by Scott Gladwell and maintained and updated by Robert J. Anderson. Packages/smartApps/smartBroadcast: A highly efficient version of packet based communication for connecting distributedmore » SMART and Umbra systems together using UDP broadcasts.« less

  2. Quality of Smartphone Apps Related to Panic Disorder

    PubMed Central

    Van Singer, Mathias; Chatton, Anne; Khazaal, Yasser

    2015-01-01

    Quality of smartphone apps related to panic: smartphone apps have a growing role in health care. This study assessed the quality of English-language apps for panic disorder (PD) and compared paid and free apps. Keywords related to PD were entered into the Google Play Store search engine. Apps were assessed using the following quality indicators: accountability, interactivity, self-help score (the potential of smartphone apps to help users in daily life), and evidence-based content quality. The Brief DISCERN score and the criteria of the “Health on the Net” label were also used as content quality indicators as well as the number of downloads. Of 247 apps identified, 52 met all inclusion criteria. The content quality and self-help scores of these PD apps were poor. None of the assessed indicators were associated with payment status or number of downloads. Multiple linear regressions showed that the Brief DISCERN score significantly predicted the content quality and self-help scores. Poor content quality and self-help scores of PD smartphone apps highlight the gap between their technological potential and the overall quality of available products. PMID:26236242

  3. The App Map: A Tool for Systematic Evaluation of Apps for Early Literacy Learning

    ERIC Educational Resources Information Center

    Israelson, Madeleine Heins

    2015-01-01

    As portable devices become increasingly available in elementary classrooms teachers are expected to use these new technologies to engage students in both traditional print-based literacy learning and digital literacies practices, such as multimodal composing. Teachers face the daunting task of integrating apps into their current research-based…

  4. Influence of Coding Variability in APP-Aβ Metabolism Genes in Sporadic Alzheimer's Disease.

    PubMed

    Sassi, Celeste; Ridge, Perry G; Nalls, Michael A; Gibbs, Raphael; Ding, Jinhui; Lupton, Michelle K; Troakes, Claire; Lunnon, Katie; Al-Sarraj, Safa; Brown, Kristelle S; Medway, Christopher; Lord, Jenny; Turton, James; Morgan, Kevin; Powell, John F; Kauwe, John S; Cruchaga, Carlos; Bras, Jose; Goate, Alison M; Singleton, Andrew B; Guerreiro, Rita; Hardy, John

    2016-01-01

    The cerebral deposition of Aβ42, a neurotoxic proteolytic derivate of amyloid precursor protein (APP), is a central event in Alzheimer's disease (AD)(Amyloid hypothesis). Given the key role of APP-Aβ metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, Aβ degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 332 sporadic and mainly late-onset AD cases and 676 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, none of which statistically significant after multiple testing correction (1.9e-4APP trafficking and recycling (SORL1). These results were partially replicated in the gene-based analysis (c-alpha and SKAT tests), that reports ECE1, LYZ and TTR as nominally associated to AD (1.7e-3 APP-Aβ genes is not a critical factor for AD development and 2) Aβ degradation and clearance, rather than Aβ production, may play a key role in the etiology of sporadic AD. PMID:27249223

  5. Influence of Coding Variability in APP-Aβ Metabolism Genes in Sporadic Alzheimer’s Disease

    PubMed Central

    Sassi, Celeste; Ridge, Perry G.; Nalls, Michael A.; Gibbs, Raphael; Ding, Jinhui; Lupton, Michelle K.; Troakes, Claire; Lunnon, Katie; Al-Sarraj, Safa; Brown, Kristelle S.; Medway, Christopher; Lord, Jenny; Turton, James; Morgan, Kevin; Powell, John F.; Kauwe, John S.; Cruchaga, Carlos; Bras, Jose; Goate, Alison M.; Singleton, Andrew B.; Guerreiro, Rita; Hardy, John

    2016-01-01

    The cerebral deposition of Aβ42, a neurotoxic proteolytic derivate of amyloid precursor protein (APP), is a central event in Alzheimer’s disease (AD)(Amyloid hypothesis). Given the key role of APP-Aβ metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, Aβ degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 332 sporadic and mainly late-onset AD cases and 676 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, none of which statistically significant after multiple testing correction (1.9e-4APP trafficking and recycling (SORL1). These results were partially replicated in the gene-based analysis (c-alpha and SKAT tests), that reports ECE1, LYZ and TTR as nominally associated to AD (1.7e-3 APP-Aβ genes is not a critical factor for AD development and 2) Aβ degradation and clearance, rather than Aβ production, may play a key role in the etiology of sporadic AD. PMID:27249223

  6. CNS amyloid-β, soluble APP-α and -β kinetics during BACE inhibition.

    PubMed

    Dobrowolska, Justyna A; Michener, Maria S; Wu, Guoxin; Patterson, Bruce W; Chott, Robert; Ovod, Vitaliy; Pyatkivskyy, Yuriy; Wildsmith, Kristin R; Kasten, Tom; Mathers, Parker; Dancho, Mandy; Lennox, Christina; Smith, Brad E; Gilberto, David; McLoughlin, Debra; Holder, Daniel J; Stamford, Andrew W; Yarasheski, Kevin E; Kennedy, Matthew E; Savage, Mary J; Bateman, Randall J

    2014-06-11

    BACE, a β-secretase, is an attractive potential disease-modifying therapeutic strategy for Alzheimer's disease (AD) as it results directly in the decrease of amyloid precursor protein (APP) processing through the β-secretase pathway and a lowering of CNS amyloid-β (Aβ) levels. The interaction of the β-secretase and α-secretase pathway-mediated processing of APP in the rhesus monkey (nonhuman primate; NHP) CNS is not understood. We hypothesized that CNS inhibition of BACE would result in decreased newly generated Aβ and soluble APPβ (sAPPβ), with increased newly generated sAPPα. A stable isotope labeling kinetics experiment in NHPs was performed with a (13)C6-leucine infusion protocol to evaluate effects of BACE inhibition on CNS APP processing by measuring the kinetics of sAPPα, sAPPβ, and Aβ in CSF. Each NHP received a low, medium, or high dose of MBI-5 (BACE inhibitor) or vehicle in a four-way crossover design. CSF sAPPα, sAPPβ, and Aβ were measured by ELISA and newly incorporated label following immunoprecipitation and liquid chromatography-mass spectrometry. Concentrations, kinetics, and amount of newly generated APP fragments were calculated. sAPPβ and sAPPα kinetics were similar, but both significantly slower than Aβ. BACE inhibition resulted in decreased labeled sAPPβ and Aβ in CSF, without observable changes in labeled CSF sAPPα. ELISA concentrations of sAPPβ and Aβ both decreased and sAPPα increased. sAPPα increased by ELISA, with no difference by labeled sAPPα kinetics indicating increases in product may be due to APP shunting from the β-secretase to the α-secretase pathway. These results provide a quantitative understanding of pharmacodynamic effects of BACE inhibition on NHP CNS, which can inform about target development. PMID:24920637

  7. Biosynthesis and regulation of rat alpha 1-inhibitor3, a negative acute-phase reactant of the macroglobulin family.

    PubMed Central

    Geiger, T; Lamri, Y; Tran-Thi, T A; Gauthier, F; Feldmann, G; Decker, K; Heinrich, P C

    1987-01-01

    The biosynthesis of rat alpha 1-inhibitor3, a negative acute-phase reactant specifically found in rodents, was studied in vitro in a cell-free translation system from rabbit reticulocytes, in rat hepatocyte primary cultures and in vivo by immunocytochemistry using normal and turpentine-injected rats. By sucrose-gradient centrifugation and subsequent translation of the fractionated RNA in vitro it was found that the mRNA coding for alpha 1-inhibitor3 exhibited a size of about 28S. For the alpha 1-inhibitor3 translated in vitro an apparent Mr of 155,000 was determined. A continuous decrease in the level of alpha 1-inhibitor3 in serum during experimental inflammation induced by turpentine injection was demonstrated by means of quantitative 'rocket' immunoelectrophoresis. This result agrees with the observation by immunocytochemistry of a drastic decrease in alpha 1-inhibitor3 levels in hepatocytes 24 h after turpentine injection. At that time alpha 1-inhibitor3 is mainly located in the Golgi apparatus, whereas it is also present in the membranes of the rough and smooth endoplasmic reticulum when normal liver is used. All hepatocytes, but no other hepatic cells, contain alpha 1-inhibitor3. When hepatocyte primary cultures were labelled with [35S]methionine and alpha 1-inhibitor3 was immunoprecipitated from the hepatocyte medium and the supernatant of homogenized cells, two different forms of alpha 1-inhibitor3 were found. The intracellular form of alpha 1-inhibitor3, with an apparent Mr of 173,000, is characterized by oligosaccharide side chains of the high-mannose type. The form of alpha 1-inhibitor3 in the medium exhibited an Mr of 186,000 and carried carbohydrate side chains of the complex type. After labelling hepatocytes with radioactive sugars, [3H]mannose was found in both forms of alpha 1-inhibitor3, whereas [3H]fucose and [3H]galactose were incorporated only into the form found in the medium. In the presence of tunicamycin an unglycosylated alpha 1-inhibitor3

  8. Medical relief activities conducted by Nippon Medical School in the acute phase of the Great East Japan Earthquake 2011.

    PubMed

    Fuse, Akira; Shuto, Yuki; Ando, Fumihiko; Shibata, Masafumi; Watanabe, Akihiro; Onda, Hidetaka; Masuno, Tomohiko; Yokota, Hiroyuki

    2011-01-01

    At 14:46 on March 11, 2011, the Great East Japan Earthquake and tsunami occurred off the coast of Honshu, Japan. In the acute phase of this catastrophe, one of our teams was deployed as a Tokyo Disaster Medical Assistance Team (DMAT) to Kudan Kaikan in Tokyo, where the ceiling of a large hall had partially collapsed as the result of the earthquake, to conduct triage at the scene: 6 casualties were assigned to the red category (immediate), which included 1 case of cardiopulmonary arrest and 1 of flail chest; 8 casualties in the yellow category (delayed); and 22 casualties in the green category (minor). One severely injured person was transported to our hospital. Separately, our medical team was deployed to Miyagi 2 hours after the earthquake in our multipurpose medical vehicle as part of Japan DMAT (J-DMAT). We were the first DMAT from the metropolitan area to arrive, but we were unable to start medical relief activities because the information infrastructure had been destroyed and no specific information had yet reached the local headquarters. Early next morning, J-DMAT decided to support Sendai Medical Center and search and rescue efforts in the affected area and to establish a staging care unit at Camp Kasuminome of the Japan Self-Defense Force. Our team joined others to establish the staging care unit. Because information was still confused until day 3 of the disaster and we could not adequately grasp onsite medical needs, our J-DMAT decided to provide onsite support at Ishinomaki Red Cross Hospital, a disaster base hospital, and relay information about its needs to the local J-DMAT headquarters. Although our medical relief teams were deployed as quickly as possible, we could not begin medical relief activities immediately owing to the severely damaged information infrastructure. Only satellite mobile phones could be operated, and information on the number of casualties and the severity of shortages of lifeline services could be obtained only through a "go and

  9. Medical relief activities conducted by Nippon Medical School in the acute phase of the Great East Japan Earthquake 2011.

    PubMed

    Fuse, Akira; Shuto, Yuki; Ando, Fumihiko; Shibata, Masafumi; Watanabe, Akihiro; Onda, Hidetaka; Masuno, Tomohiko; Yokota, Hiroyuki

    2011-01-01

    At 14:46 on March 11, 2011, the Great East Japan Earthquake and tsunami occurred off the coast of Honshu, Japan. In the acute phase of this catastrophe, one of our teams was deployed as a Tokyo Disaster Medical Assistance Team (DMAT) to Kudan Kaikan in Tokyo, where the ceiling of a large hall had partially collapsed as the result of the earthquake, to conduct triage at the scene: 6 casualties were assigned to the red category (immediate), which included 1 case of cardiopulmonary arrest and 1 of flail chest; 8 casualties in the yellow category (delayed); and 22 casualties in the green category (minor). One severely injured person was transported to our hospital. Separately, our medical team was deployed to Miyagi 2 hours after the earthquake in our multipurpose medical vehicle as part of Japan DMAT (J-DMAT). We were the first DMAT from the metropolitan area to arrive, but we were unable to start medical relief activities because the information infrastructure had been destroyed and no specific information had yet reached the local headquarters. Early next morning, J-DMAT decided to support Sendai Medical Center and search and rescue efforts in the affected area and to establish a staging care unit at Camp Kasuminome of the Japan Self-Defense Force. Our team joined others to establish the staging care unit. Because information was still confused until day 3 of the disaster and we could not adequately grasp onsite medical needs, our J-DMAT decided to provide onsite support at Ishinomaki Red Cross Hospital, a disaster base hospital, and relay information about its needs to the local J-DMAT headquarters. Although our medical relief teams were deployed as quickly as possible, we could not begin medical relief activities immediately owing to the severely damaged information infrastructure. Only satellite mobile phones could be operated, and information on the number of casualties and the severity of shortages of lifeline services could be obtained only through a "go and

  10. Public Health Guidelines for Physical Activity: Is There an App for That? A Review of Android and Apple App Stores

    PubMed Central

    2015-01-01

    Background Physical activity participation is an important behavior for modifying lifestyle-related disease risk. Mobile health apps for chronic disease management and prevention are being developed at a rapid rate. However, it is unclear whether these apps are evidence-based. Current public health recommendations for physical activity participation for adults highlight the importance of engaging in 150 minutes weekly of purposeful exercise, and muscle strengthening activities on at least 2 days of the week. Objective The aims of the present review were to (1) identify available evidence-based physical activity apps, and (2) identify technological features that could be leveraged to improve health outcomes. Methods iTunes and Google Play mobile app stores were searched using keyword and category searching during a single day (February 18, 2014) for physical activity apps available in English. The description pages of eligible apps were reviewed by 4 independent reviewers for evidence-based content, technological, and descriptive features. An a priori subset of apps was downloaded for further review (n=6 affiliated with a non-commercial agency; n=10 top rated; n=10 random selection), and developers were contacted for information regarding evidence-informed content. Results The initial search yielded 2400 apps, of which 379 apps (n=206 iTunes; n=173 Google Play) were eligible. Primary results demonstrated no apps (n=0) adhering to evidence-based guidelines for aerobic physical activity, and 7 out of 379 implementing evidence-based guidelines for resistance training physical activity. Technological features of apps included social networking (n=207), pairing with a peripheral health device (n=61), and measuring additional health parameters (n=139). Secondary results revealed 1 app that referenced physical activity guidelines (150 minutes/weekly of exercise), and demonstrated that apps were based on various physical activity reports (n=4) or personal expertise (n=2

  11. Cellular signaling roles of TGF beta, TNF alpha and beta APP in brain injury responses and Alzheimer's disease.

    PubMed

    Mattson, M P; Barger, S W; Furukawa, K; Bruce, A J; Wyss-Coray, T; Mark, R J; Mucke, L

    1997-02-01

    beta-Amyloid precursor protein (beta APP), transforming growth factor beta (TGF beta), and tumor necrosis factor-alpha (TNF alpha) are remarkably pleiotropic neural cytokines/neurotrophic factors that orchestrate intricate injury-related cellular and molecular interactions. The links between these three factors include: their responses to injury; their interactive effects on astrocytes, microglia and neurons; their ability to induce cytoprotective responses in neurons; and their association with cytopathological alterations in Alzheimer's disease. Astrocytes and microglia each produce and respond to TGF beta and TNF alpha in characteristic ways when the brain is injured. TGF beta, TNF alpha and secreted forms of beta APP (sAPP) can protect neurons against excitotoxic, metabolic and oxidative insults and may thereby serve neuroprotective roles. On the other hand, under certain conditions TNF alpha and the fibrillogenic amyloid beta-peptide (A beta) derivative of beta APP can promote damage of neuronal and glial cells, and may play roles in neurodegenerative disorders. Studies of genetically manipulated mice in which TGF beta, TNF alpha or beta APP ligand or receptor levels are altered suggest important roles for each factor in cellular responses to brain injury and indicate that mediators of neural injury responses also have the potential to enhance amyloidogenesis and/or to interfere with neuroregeneration if expressed at abnormal levels or modified by strategic point mutations. Recent studies have elucidated signal transduction pathways of TGF beta (serine/threonine kinase cascades), TNF alpha (p55 receptor linked to a sphingomyelin-ceramide-NF kappa B pathway), and secreted forms of beta APP (sAPP; receptor guanylate cyclase-cGMP-cGMP-dependent kinase-K+ channel activation). Knowledge of these signaling pathways is revealing novel molecular targets on which to focus neuroprotective therapeutic strategies in disorders ranging from stroke to Alzheimer's disease

  12. Genetic influences on atrophy patterns in familial Alzheimer's disease: a comparison of APP and PSEN1 mutations.

    PubMed

    Scahill, Rachael I; Ridgway, Gerard R; Bartlett, Jonathan W; Barnes, Josephine; Ryan, Natalie S; Mead, Simon; Beck, Jonathan; Clarkson, Matthew J; Crutch, Sebastian J; Schott, Jonathan M; Ourselin, Sebastien; Warren, Jason D; Hardy, John; Rossor, Martin N; Fox, Nick C

    2013-01-01

    Mutations in the presenilin1 (PSEN1) and amyloid β-protein precursor (APP) genes account for the majority of cases of autosomal dominantly inherited Alzheimer's disease (AD). We wished to assess and compare the patterns of cerebral loss produced by these two groups of mutations. Volumetric magnetic resonance imaging and neuropsychological assessments were performed in individuals with clinical AD carrying mutations in the APP (n = 10) and PSEN1 (n = 18) genes and in healthy controls (n = 18). Voxel-based morphometry (VBM), cortical thickness, and region of interest analyses were performed. Mini-Mental State Examination scores were similar in the two disease groups suggesting similar levels of disease severity. There was evidence that APP subjects have smaller hippocampal volume compared with PSEN1 subjects (p = 0.007), and weak evidence that they have larger whole-brain and grey matter volumes (both p = 0.07). Although there was no evidence of statistically significant differences between APP and PSEN1 in VBM or cortical thickness analyses, effect-maps were suggestive of APP subjects having more medial temporal lobe atrophy and conversely PSEN1 subjects showing more neocortical loss. Neuropsychological data were consistent with these regional differences and suggested greater memory deficits in the APP patients and greater impairment in non-memory domains in the PSEN1 group, although these differences were not statistically significant. We conclude that the mechanisms by which APP and PSEN1 mutations cause neuronal loss may differ which furthers our understanding of the neuropathology underlying AD and may inform future therapeutic strategies and trial designs. PMID:23380992

  13. 76 FR 49485 - Announcement of Requirements and Registration for “Lifeline Facebook App Challenge”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-10

    ... HUMAN SERVICES Announcement of Requirements and Registration for ``Lifeline Facebook App Challenge...: The ``Lifeline Facebook App Challenge'' is a challenge aimed at multidisciplinary teams of technology... Facebook as a platform for connecting individuals together through an application (app) that will...

  14. Isolation Housing Exacerbates Alzheimer’s Disease-Like Pathophysiology in Aged APP/PS1 Mice

    PubMed Central

    Huang, Huang; Wang, Linmei; Cao, Min; Marshall, Charles; Gao, Junying; Xiao, Na; Hu, Gang

    2015-01-01

    Background: Alzheimer’s disease is a neurodegenerative disease characterized by gradual declines in social, cognitive, and emotional functions, leading to a loss of expected social behavior. Social isolation has been shown to have adverse effects on individual development and growth as well as health and aging. Previous experiments have shown that social isolation causes an early onset of Alzheimer’s disease-like phenotypes in young APP695/PS1-dE9 transgenic mice. However, the interactions between social isolation and Alzheimer’s disease still remain unknown. Methods: Seventeen-month-old male APP695/PS1-dE9 transgenic mice were either singly housed or continued group housing for 3 months. Then, Alzheimer’s disease-like pathophysiological changes were evaluated by using behavioral, biochemical, and pathological analyses. Results: Isolation housing further promoted cognitive dysfunction and Aβ plaque accumulation in the hippocampus of aged APP695/PS1-dE9 transgenic mice, associated with increased γ-secretase and decreased neprilysin expression. Furthermore, exacerbated hippocampal atrophy, synapse and myelin associated protein loss, and glial neuroinflammatory reactions were observed in the hippocampus of isolated aged APP695/PS1-dE9 transgenic mice. Conclusions: The results demonstrate that social isolation exacerbates Alzheimer’s disease-like pathophysiology in aged APP695/PS1-dE9 transgenic mice, highlighting the potential role of group life for delaying or counteracting the Alzheimer’s disease process. PMID:25568286

  15. A Comprehensive Evaluation Rubric for Assessing Instructional Apps

    ERIC Educational Resources Information Center

    Lee, Cheng-Yuan; Cherner, Todd Sloan

    2015-01-01

    There is a pressing need for an evaluation rubric that examines all aspects of educational apps designed for instructional purposes. In past decades, many rubrics have been developed for evaluating educational computer-based programs; however, rubrics designed for evaluating the instructional implications of educational apps are scarce. When an…

  16. Availability and quality of mobile health app privacy policies.

    PubMed

    Sunyaev, Ali; Dehling, Tobias; Taylor, Patrick L; Mandl, Kenneth D

    2015-04-01

    Mobile health (mHealth) customers shopping for applications (apps) should be aware of app privacy practices so they can make informed decisions about purchase and use. We sought to assess the availability, scope, and transparency of mHealth app privacy policies on iOS and Android. Over 35,000 mHealth apps are available for iOS and Android. Of the 600 most commonly used apps, only 183 (30.5%) had privacy policies. Average policy length was 1755 (SD 1301) words with a reading grade level of 16 (SD 2.9). Two thirds (66.1%) of privacy policies did not specifically address the app itself. Our findings show that currently mHealth developers often fail to provide app privacy policies. The privacy policies that are available do not make information privacy practices transparent to users, require college-level literacy, and are often not focused on the app itself. Further research is warranted to address why privacy policies are often absent, opaque, or irrelevant, and to find a remedy. PMID:25147247

  17. [Diabetes mellitus: Which risks do smartphone apps have?].

    PubMed

    Keuthage, Winfried

    2015-08-01

    Medical apps are increasingly used by patients and doctors. However, it lacks systematic studies that deal with potential hazards. In a recent study, two-thirds of the examined insulin bolus calculator apps were associated with some major risks for the patient.

  18. "Apps"--An Innovative Way to Share Extension Knowledge

    ERIC Educational Resources Information Center

    Dvorak, Joseph S.; Franke-Dvorak, Tanya C.; Price, Randy R.

    2012-01-01

    Extension professionals across the country are continuously seeking innovative ways to rea