Craig, D G; Lee, P; Pryde, E A; Hayes, P C; Simpson, K J
2013-12-01
Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages. To examine neopterin and sCD163 levels in a cohort of acute liver injury patients. Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were enrolled. Neopterin and sCD163 levels were measured by ELISA. A total of 24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. Both neopterin and sCD163 levels were significantly higher in PODs compared with chronic liver disease (neopterin P < 0.001, sCD163 P = 0.038) and healthy (both P < 0.001) controls. Admission neopterin levels were significantly higher in PODs: with HE (P = 0.001); with the SIRS (P = 0.005); who required renal replacement therapy (P = 0.003); who died or required liver transplantation (P = 0.006; AUROC 78.6% (95% CI 62.2-94.9%). Serum sCD163 levels were significantly higher in those PODs with the SIRS (P = 0.033) on admission, and were higher in those PODs who died or required OLT (P = 0.024). Both admission neopterin and sCD163 levels in PODs correlated with organ failure scores but not with serum ALT. There was no significant correlation between neopterin and sCD163 values. Both serum neopterin and sCD163 levels are significantly elevated following paracetamol overdose, and reflect the degree of macrophage activation in this condition. Serum neopterin in particular may have value as an early proxy marker of macrophage activation following paracetamol overdose. © 2013 John Wiley & Sons Ltd.
Spencer, Monique E; Jain, Alka; Matteini, Amy; Beamer, Brock A; Wang, Nae-Yuh; Leng, Sean X; Punjabi, Naresh M; Walston, Jeremy D; Fedarko, Neal S
2010-08-01
Neopterin, a GTP metabolite expressed by macrophages, is a marker of immune activation. We hypothesize that levels of this serum marker alter with donor age, reflecting increased chronic immune activation in normal aging. In addition to age, we assessed gender, race, body mass index (BMI), and percentage of body fat (%fat) as potential covariates. Serum was obtained from 426 healthy participants whose age ranged from 18 to 87 years. Anthropometric measures included %fat and BMI. Neopterin concentrations were measured by competitive ELISA. The paired associations between neopterin and age, BMI, or %fat were analyzed by Spearman's correlation or by linear regression of log-transformed neopterin, whereas overall associations were modeled by multiple regression of log-transformed neopterin as a function of age, gender, race, BMI, %fat, and interaction terms. Across all participants, neopterin exhibited a positive association with age, BMI, and %fat. Multiple regression modeling of neopterin in women and men as a function of age, BMI, and race revealed that each covariate contributed significantly to neopterin values and that optimal modeling required an interaction term between race and BMI. The covariate %fat was highly correlated with BMI and could be substituted for BMI to yield similar regression coefficients. The association of age and gender with neopterin levels and their modification by race, BMI, or %fat reflect the biology underlying chronic immune activation and perhaps gender differences in disease incidence, morbidity, and mortality.
Casoni, F; Merelli, E; Bedin, R; Sola, P; Bertolotto, A; Faglioni, P
2004-01-01
Interferon beta (INFbeta) may induce the expression of several proteins, including neopterin, considered a biological marker of INFbeta activity. The aim of this study was to determine the serum neopterin concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing-remitting multiple sclerosis (r-r MS) patients, and to look for a possible correlation between protein synthesis and the clinical course of the disease. Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week) for 2 years. Blood samples for neopterin determinations were taken daily over a period of 1 week at the end of each 6 months of therapy, and tested for neutralizing antibodies (NABs). Neopterin levels peaked 24-48 h post-injection and returned to baseline after 120 h. After 1 year of therapy, four patients dropped out of the study because of progression of the disease: in these subjects a significant decrement of neopterin was observed. Neopterin baseline values were not found to decrease over the 2 years of therapy, and neopterin may be considered to be a useful marker of responsiveness to IFNbeta.
[Neopterin in serum and cerebrospinal fluid in Lyme disease].
Biesiada, Grazyna; Czepiel, Jacek; Garlicki, Aleksander; Mach, Tomasz
2009-01-01
Lyme disease is a multiorgan disease, caused by spirochetes of Borrelia species. Clinical picture is diverse, borreliosis can affect skin, nervous system, musculoskeletal system and heart. Neopterin is a marker of cytotoxic lymphocytes T activities, it is produced by monocytes/macrophages stimulated with IFNgamma. The aim of our study was to evaluate the level of neopterin in serum and cerebrospinal fluid in borreliosis and correlate it with the symptoms, markers of inflammation in cerebrospinal fluid (CSF), and serological tests against Borrelia burgdorferi. We have enrolled in the study 39 patients treated for Lyme borreliosis. The level of neopterin in serum was assessed in all patients, among patient with suspicion of neuroborreliosis (n = 33) we assessed the level of neopterin, protein, glucose and chlorium in CSF. The level of neopterin in CSF was lower among patients who were treated due to presence of erithema migrans in their past regarding patients who had never had erithema migrans (p = 0.008). The level of neopterin in CSF was higher (6.6 nmol/l) in patients with the presence of inflammation in CSF versus patients with no changes in CSF (3.8 mmol/l; p = 0.019). There was no correlation between neopterin in serum or CSF and Westernblot test. Patients with neuroborreliosis who had lymphocytic meningitis had higher level of neopterin in CSF. We suggest the role of neopterin in pathogenesis on neuroborreliosis. Neopterin as a marker of cytotoxic lymphocytes T activities can be useful in borreliosis diagnosis but more studies regarding this problem should be done.
Pleural fluid neopterin levels in tuberculous pleurisy.
Cok, Gursel; Parildar, Zuhal; Basol, Gunes; Kabaroglu, Ceyda; Bayindir, Ulku; Habif, Sara; Bayindir, Oya
2007-08-01
Neopterin is produced by stimulated macrophages under the influence of gamma interferon of lymphocyte origin. It is regarded as a biochemical marker of cell-mediated immune response. This study was designed to assess the diagnostic value of pleural fluid neopterin levels in tuberculous pleurisy in comparison with adenosine deaminase activity. Pleural fluid adenosine deaminase (ADA) activity and neopterin levels were measured in 16 patients with tuberculous pleurisy (TP) and 19 patients with malignant pleurisy (MP). ADA activity was determined by a colorimetric method, whereas neopterin levels were determined by a reversed-phase liquid chromatography technique. All values were given as median (min-max). The mean age was 45.43+/-20.39 years in the TP group and 60.42+/-11.02 years in the MP group (p=0.026). The median pleural fluid ADA activity was 51.75 U/L (3.50-62.40 U/L) in the TP group and was 2.30 U/L (1-8.20 U/L) in the MP group. The difference was statistically significant (p<0.001). The median pleural fluid neopterin levels were 13.15 nmol/L (1.86-59.50 nmol/L) and 2.44 nmol/L (0.92-27.60 nmol/L) in the TP group and the MP group, respectively (p=0.021). In order to evaluate the diagnostic value of pleural fluid neopterin concentrations, receiver-operating-characteristic curve analysis was performed. Pleural fluid neopterin concentration is significantly higher in TP when compared to MP, however when compared, its clinical use as a diagnostic marker is not valuable as ADA.
Elbarbary, Nancy Samir; Ismail, Eman Abdel Rahman; El-Hilaly, Rana Ahmed; Ahmed, Fatma Salama
2018-06-01
Neopterin, a marker of inflammation and cellular immune response, is elevated in conditions of T-cell or macrophages activation. Diabetic peripheral neuropathy (DPN) is associated with inflammatory/immune processes and therefore, we hypothesized that neopterin could be used as a marker of neuropathy in type 1 diabetes mellitus (T1DM). To measure neopterin levels in children and adolescents with T1DM and assess its possible relation to DPN and nerve conduction studies (NCS). Sixty patients aged ≤18 years and >5 years disease duration were subjected to neurological assessment by neuropathy disability score (NDS) and NCS for median, ulnar, posterior tibial and common peroneal nerves. Mean fasting blood glucose, lipid profile, HbA1c, high sensitivity C-reactive protein (hs-CRP) and serum neopterin levels were assessed. Patients were compared with 30 age- and sex-matched healthy controls. The frequency of DPN according to NDS was 40 (66.7%) patients out of 60 while NCS confirmed that only 30 of those 40 patients had this complication (i.e. 50% out of the total studied patients). Neopterin levels were significantly higher in patients with DPN than those without (median [IQR], 53.5 [35-60] nmol/L versus 17 [13-32] nmol/L) and healthy controls (5.0 [3.2-7.0] nmol/L) (p < 0.001). Significant positive correlations were found between neopterin levels and HbA1c (r = 0.560, p = 0.005), serum creatinine (r = 0.376, p = 0.003), total cholesterol (r = 0.405, p = 0.026) and hs-CRP (r = 0.425, p = 0.012) among patients with DPN. Neopterin levels were positively correlated to motor latency of tibial and common peroneal nerves as well as motor and sensory latencies of median and ulnar nerves. Logistic regression analysis revealed that neopterin was a significant independent variable related to DPN (Odds ratio, 2.976). Neopterin cutoff value 32 nmol/L could differentiate patients with and without DPN with 100% sensitivity and 96
Hagberg, Lars; Cinque, Paola; Gisslen, Magnus; Brew, Bruce J; Spudich, Serena; Bestetti, Arabella; Price, Richard W; Fuchs, Dietmar
2010-06-03
HIV-1 invades the central nervous system (CNS) in the context of acute infection, persists thereafter in the absence of treatment, and leads to chronic intrathecal immunoactivation that can be measured by the macrophage activation marker, neopterin, in cerebrospinal fluid (CSF). In this review we describe our experience with CSF neopterin measurements in 382 untreated HIV-infected patients across the spectrum of immunosuppression and HIV-related neurological diseases, in 73 untreated AIDS patients with opportunistic CNS infections, and in 233 treated patients.In untreated patients, CSF neopterin concentrations are almost always elevated and increase progressively as immunosuppression worsens and blood CD4 cell counts fall. However, patients with HIV dementia exhibit particularly high CSF neopterin concentrations, above those of patients without neurological disease, though patients with CNS opportunistic infections, including CMV encephalitis and cryptococcal meningitis, also exhibit high levels of CSF neopterin. Combination antiretroviral therapy, with its potent effect on CNS HIV infection and CSF HIV RNA, mitigates both intrathecal immunoactivation and lowers CSF neopterin. However, despite suppression of plasma and CSF HIV RNA to below the detection limits of clinical assays (<50 copies HIV RNA/mL), CSF neopterin often remains mildly elevated, indicating persistent low-level intrathecal immune activation and raising the important questions of whether this elevation is driven by continued CNS infection and whether it causes continued indolent CNS injury.Although nonspecific, CSF neopterin can serve as a useful biomarker in the diagnosis of HIV dementia in the setting of confounding conditions, in monitoring the CNS inflammatory effects of antiretroviral treatment, and give valuable information to the cause of ongoing brain injury.
High plasma neopterin levels in Chinese children with autism spectrum disorders.
Zhao, Hong-xiang; Yin, Sha-sha; Fan, Jin-gang
2015-04-01
Neopterin, a pteridine mainly synthesized by activated macrophages, is a marker of inflammation, immune system activation and an active participant in Autism spectrum disorders (ASD). The aim of this study was to assess the clinical significance of plasma neopterin levels in ASD. Eighty patients diagnosed with ASD and 80 sex and age matched typically developing children were assessed for plasma levels of neopterin at admission. Plasma neopterin levels were measured using a human ELISA kit and severity of ASD were evaluated with the Childhood Autism Rating Scale (CARS) score. We found that the mean plasma neopterin level was significantly (P<0.0001) higher in children with ASD as compared to controls. Plasma neopterin increased with increasing severity of ASD as defined by the CARS score. Based on the ROC curve, the optimal cutoff value of plasma neopterin level as an indicator for auxiliary diagnosis of ASD was projected to be 8.5nmol/L, which yielded a sensitivity of 84.2% and a specificity of 80.1%, with the area under the curve at 0.876 (95% CI, 0.825-0.928). Elevated neopterin (≥8.5nmol/L) was an independent diagnosis indicator of ASD with an adjusted OR of 12.11 (95% CI: 5.48-28.11; P<0.0001). These results indicated that autistic children had higher plasma levels of neopterin, and elevated plasma neopterin levels may be associated with severity of ASD among Chinese children. Copyright © 2015 Elsevier Ltd. All rights reserved.
Seasonality of blood neopterin levels in the Old Order Amish
Mohyuddin, Hira; Georgiou, Polymnia; Wadhawan, Abhishek; Daue, Melanie L.; Brenner, Lisa A.; Gragnoli, Claudia; Saunders, Erika F.H.; Fuchs, Dietmar; Lowry, Christopher A.
2018-01-01
Seasonal changes in non-human animals and seasonal affective disorder (SAD) in humans are associated with immune activation in winter relative to summer. We intended to measure seasonal variation in neopterin, a marker of cellular immunity, and its interactions with gender and seasonality of mood. We studied 320 Amish from Lancaster, PA, USA (men = 128; 40%) with an average age [Standard deviation (SD)] of 56.7 (13.9) years. Blood neopterin level was measured with enzyme-linked immunosorbent assay (ELISA). Seasonality was measured with Seasonal Pattern Assessment Questionnaire (SPAQ). Statistical analysis included analysis of covariance (ANCOVAs) and multivariate linear regression. We also investigated interactions of seasonal differences in neopterin with gender, seasonality scores and estimation of SAD diagnosis. We found a significantly higher neopterin level in winter than in summer (p = 0.006). There were no significant gender or seasonality interactions. Our study confirmed the hypothesized higher neopterin level in winter. A cross sectional design was our major limitation. If this finding will be replicated by longitudinal studies in multiple groups, neopterin could be used to monitor immune status across seasons in demographically diverse samples, even if heterogeneous in gender distribution, and degree of seasonality of mood. PMID:29657362
Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS patients.
Cook, S D; Quinless, J R; Jotkowitz, A; Beaton, P
2001-09-25
To determine levels of serum interferon beta (IFNbeta) neutralizing antibody (NAb) and neopterin-an IFN biologic response marker-in patients with MS treated with Betaseron or Avonex. Controversy exists over the relative immunogenicity of IFNbeta-1a and IFNbeta-1b and the reasons for any such difference. To determine the role of patient profile and test methodology in IFNbeta, NAb levels need to be measured blindly and simultaneously in a predefined closely matched MS patient cohort. Serum NAb and neopterin levels were measured in closely matched patients on Avonex (n = 98) or Betaseron (n = 64). NAb were determined by Athena Diagnostics and serum neopterin levels by Covance Laboratories using a competitive binding radioimmunoassay. More patients taking Betaseron (22%) than Avonex (7%) had elevated titers of NAb (p = 0.008). Mean serum neopterin levels were lower in patients with high as compared to low NAb titers (p = 0.0002). No difference in mean neopterin levels was found comparing the total Betaseron group to the Avonex group; however, in the subset of patients with low NAb titers, mean neopterin levels were higher in the Betaseron than in the Avonex group (p = 0.027). A random cross-sectional sampling of patients on Avonex showed a decrease in neopterin levels over time between weekly doses. NAb are more commonly found with Betaseron than Avonex. More studies are needed to determine the correlation among serum neopterin levels, other biologic response markers, NAb, and disease activity in patients with MS being treated with IFNbeta.
Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy.
Yilmaz, Aylin; Yiannoutsos, Constantin T; Fuchs, Dietmar; Price, Richard W; Crozier, Kathryn; Hagberg, Lars; Spudich, Serena; Gisslén, Magnus
2013-05-10
Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.
Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy
2013-01-01
Background Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. Methods CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation. PMID:23664008
Evaluation of neopterin as a biomarker for the monitoring of Gaucher disease patients.
Drugan, Cristina; Drugan, Tudor C; Miron, Nicolae; Grigorescu-Sido, Paula; Naşcu, Ioana; Cătană, Cristina
2016-07-01
Biomarker research is an important area of investigation in Gaucher disease, caused by an inherited deficiency of a lysosomal enzyme, glucocerebrosidase. We evaluated the usefulness of neopterin, as a novel biomarker reflecting chronic inflammation and immune system activation in Gaucher disease and analysed its evolution in response to enzyme replacement therapy (ERT). Circulating plasma neopterin levels in 31 patients with non-neuronopathic Gaucher disease were measured before and after the onset of ERT and were compared with those of 18 healthy controls. Plasma chitotriosidase activity was also monitored, as a reference biomarker, against which we evaluated the evolution of neopterin. Neopterin levels were significantly increased in treatment-naïve patients (mean 11.90 ± 5.82 nM) compared with controls (6.63 ± 5.59 nM, Mann-Whitney U test P = 0.001), but returned to normal levels (6.92 ± 4.66 nM) following ERT. Investigating the diagnostic value of neopterin by receiver operating characteristic analysis, we found a cut-off value of 7.613 nM that corresponds to an area under the curve of 0.780 and indicates a good discrimination capacity, with a sensitivity of 0.774 and a specificity of 0.778. Our results suggest that measurement of circulating neopterin may be considered as a novel test for the confirmation of diagnosis and monitoring of the efficacy of therapeutic intervention in Gaucher disease. Plasma neopterin levels reflect the global accumulation and activation of Gaucher cells and the extent of chronic immune activation in this disorder. Neopterin may be an alternative storage cell biomarker in Gaucher disease, especially in chitotriosidase-deficient patients.
Faber, W R; Iyer, A M; Fajardo, T T; Dekker, T; Villahermosa, L G; Abalos, R M; Das, P K
2004-09-01
Serum levels of cytokines (IL-4, IL-5, IFN-gamma, TNF-alpha), cytokine receptors (TNFR I and II) and one monokine (neopterin) were estimated in seven leprosy patients to establish disease associated markers for reversal reactions (RR). Sera were collected at diagnosis of leprosy, at the onset of reversal reaction and at different time points during and at the end of prednisone treatment of reactions. It was expected that the serum cytokine and monokine profile before and at different time points during reactions would provide guidelines for the diagnosis and monitoring of reversal reactions in leprosy. The cytokines and cytokine receptors were measured by ELISA, whereas a radioimmunoassay was used for neopterin measurement. Six of the seven patients showed increased levels of neopterin either at the onset of RR or 1 month thereafter, and levels declined on prednisone treatment to that seen at the time of diagnosis without reactions. No consistent disease associated cytokine profile was observed in these patients. Interestingly, serum TNF-alpha levels were increased in the same patients even after completion of prednisone treatment, indicating ongoing immune activity. In conclusion, this study demonstrates that despite cytokines levels in leprosy serum being inconsistent in relation to reversal reactions, serum neopterin measurement appears to be an useful biomarker in monitoring RR patients during corticosteroid therapy.
Prasanna, Jammula Surya; Sumadhura, Chinta; Karunakar, Parupalli; Rekharani, Koduganti; Himabindu, Gireddy; Manasa, Ambati
2017-01-01
Periodontitis is an inflammatory condition which is distinguished by the devastation of the supported tooth structures. In such inflammatory conditions, some biomarkers such as neopterin will be secreted and elevated in the body fluids, which can be used as a diagnostic marker for the present and future disease activity. Assessment of the neopterin as a biomarker in inflammatory conditions such as menopause and periodontitis. A cross-sectional interventional study. Sixty female individuals with a mean age of 40-60 years with chronic periodontitis were included in this study. All were categorized into two groups of thirty each, depending on their menstrual history: Group I - thirty premenopausal women and Group II - thirty postmenopausal women. Urine and plasma were collected from both groups to estimate neopterin levels. ELISA kit was used to assess the neopterin levels at baseline and after 3 months of nonsurgical periodontal therapy (NSPT). IBM SPSS version 21 software. A significant depreciation in the mean values of all the parameters from baseline to 3 months ( P < 0.001), in the intragroup analysis, was observed. Plasma (0.006) and urine (0.004) reduction was seen. In both the groups, in 3 months after NSPT, decreased neopterin levels were found, suggesting that the NSPT is the definitive therapy. Further, suggesting that, neopterin levels in the plasma and urine can be used as an index to identify the periodontal inflammation and destruction.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schroecksnadel, Sebastian; Jenny, Marcel; Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck
2010-09-03
Research highlights: {yields} LPS induces NF-{kappa}B, neopterin formation and tryptophan degradation in THP-1 cells. {yields} Close dose- and time-dependent correlations exist between these biochemical events. {yields} Data provides some evidence for a parallel induction of them upon TLR stimulation. {yields} Results can be of considerable relevance also in vivo. -- Abstract: Neopterin production is induced in human monocyte-derived macrophages and dendritic cells upon stimulation with Th1-type cytokine interferon-{gamma} (IFN-{gamma}). In parallel, IFN-{gamma} induces the tryptophan-(trp)-degrading enzyme indoleamine 2,3-dioxygenase (IDO) and triggers the formation of reactive oxygen species (ROS). Translocation of the signal transduction element nuclear factor-{kappa}B (NF-{kappa}B) is induced bymore » ROS and accelerates the pro-inflammatory response by activation of other pro-inflammatory pathways. Therefore, a close relationship between NF-{kappa}B expression, the production of neopterin and the degradation of trp can be assumed, although this has not been demonstrated so far. In the present in vitro study we compared the influence of lipopolysaccharide (LPS) on NF-{kappa}B activation, neopterin formation and the degradation of trp in THP-1Blue cells, which represent the human myelomonocytic cell line THP-1 stably transfected with an NF-{kappa}B inducible reporter system. In cells stimulated with LPS, a significant induction of NF-{kappa}B was observed, and this was paralleled by an increase of kynureunine (kyn) and neopterin concentrations and a decline of trp. The increase of the kyn to trp quotient indicates accelerated IDO activity. Higher LPS concentrations and longer incubation of cells were associated with higher activities of all three biochemical pathways and significant correlations existed between NF-{kappa}B activation, neopterin release and trp degradation (all p < 0.001). We conclude that there is a parallel induction of NF-{kappa}B, neopterin
Estimation of salivary neopterin in chronic periodontitis.
Mahendra, Little; Mahendra, Jaideep; Borra, Sai Krishna; Nagarajan, Aishwarya
2014-01-01
Periodontal diseases are the most common bacterial infection predominantly associated with Gram-negative microorganisms that exist in the subgingival biofilm. Analysis of saliva provides a noninvasive means of evaluating the role of the host response in periodontal disease. Though salivary enzymes can be used as the biomarkers, neopterin has been recently used as one of the important diagnostic tools in the field of periodontics. Hence, we aimed to identify the neopterin levels in unsimulated saliva from the chronic periodontitis patients and compare them with the periodontally healthy subjects. Twenty subjects participated in the study and were categorized as the experimental group (chronic periodontitis patients) and control groups (healthy subjects). Unstimulated saliva samples were collected from both the groups for neopterin estimation. Neopterin in saliva was estimated using Shimadzu High Performance Liquid Chromatography with LC-20AD pump system, equipped with RF-10 AXL fluorescence detector. Data were expressed as mean±SD and analyzed using GraphPad Prism version 6.0 (California, USA). Statistical analysis was done by Student's t-test. The neopterin level in unstimulated saliva was found to be higher in the experimental group than the control group with P≤0.05. The chronic periodontitis patients showed higher neopterin level in unstimulated saliva as compared to control. Hence, neopterin can be used as a potential biomarker for identification of the periodontal disease in its initial stage can help in preventing the disease progression.
Sipahi, Hande; Becker, Kathrin; Gostner, Johanna M; Charehsaz, Mohammad; Kirmizibekmez, Hasan; Schennach, Harald; Aydin, Ahmet; Fuchs, Dietmar
2014-01-01
The potential effects of globularifolin, an acylated iridoid glucoside, on cell survival, inflammation markers and free radicals scavenging were investigated. Viability assay on human myelomomonocytic cell line THP-1 and human peripheral blood mononuclear cells (PBMC) using the Cell-Titer Blue assay proved that globularifolin had no toxic effect at the tested concentrations. Conversely, it is proportional to the dose globularifolin increased growth of THP-1 cells (p <0.01). On human PBMC, globularifolin at 6.25 and 12.5 μM concentrations showed a stimulatory effect, while at 12.5-200 μM it suppressed response of PBMC to stimulation with phytohemagglutinin (PHA). Globularifolin (50-200 μM) enhanced neopterin formation dose-dependently, whereas tryptophan breakdown was not influenced. At 50-200 μM in unstimulated PBMC in THP-1 cells, globularifolin induced a significant expression of nuclear factor-κB (NF-κB) as was quantified by Quanti-Blue assay. By contrast, in lipopolysaccharide (LPS)-stimulated cells, the higher concentrations of globularifolin suppressed NF-κB expression dose-dependently and a significant decrease was observed at 200 μM concentration. A positive correlation was found between increased neopterin and NF-κB activity (p <0.01). Similarly, a positive correlation was observed between neopterin levels in mitogen-induced cells and NF-κB activity in LPS-stimulated cells after treatment with globularifolin (p=0.001). The free radical scavenging capacity of globularifolin evaluated by Oxygen Radical Absorbance Capacity (ORAC) assay showed relative ORAC values of 0.36±0.05 μmol Trolox equivalent/μmol. All together, results show that natural antioxidant globularifolin might represent a potential immunomodulatory as well as proliferative agent, which deserves further in vitro and in vivo studies. © 2013.
Evaluation of procalcitonin and neopterin level in serum of patients with acute bacterial infection.
Pourakbari, Babak; Mamishi, Setareh; Zafari, Javid; Khairkhah, Hanieh; Ashtiani, Mohammad H; Abedini, Masomeh; Afsharpaiman, Shahla; Rad, Soroush Seifi
2010-01-01
Fever as a common presenting complaint in pediatric patients can be due to various causes. Differentiating bacterial infection from other causes is important because the prompt use of antibiotics is critical in bacterial infection. Traditional markers of infection such as BT and WBC count may be unspecific and culture may be late or absent. CRP and Procalcitonin (PCT) have been considered to evaluate the evolution of infections and sepsis in patients presenting with SIRS. Neopterin has also been proposed to aid in the diagnosis of bacterial infection. In this study, we compared the value of the serum PCT, neopterin level, and WBC count for predicting bacterial infection and outcome in children with fever. 158 pediatric (2-120-month-old) patients suspected to have acute bacterial infection, based on clinical judgment in which other causes of SIRS were ruled out were included in the study. WBC count with differential was determined and PCT and neopterin levels were measured. PCT level was higher in bacterial infection and patients who were complicated or expired. Rapid PCT test is superior to neopterin and WBC count for anticipating bacterial infection, especially in ED where prompt decision making is critical.
Beryllium-stimulated neopterin as a diagnostic adjunct in chronic beryllium disease.
Maier, Lisa A; Kittle, Lori A; Mroz, Margaret M; Newman, Lee S
2003-06-01
The diagnosis of chronic beryllium disease (CBD) relies on the beryllium lymphocyte proliferation test (BeLPT) to demonstrate a Be specific immune response. This test has improved early diagnosis, but cannot discriminate beryllium sensitization (BeS) from CBD. We previously found high neopterin levels in CBD patients' serum and questioned whether Be-stimulated neopterin production by peripheral blood cells in vitro might be useful in the diagnosis of CBD. CBD, BeS, Be exposed workers without disease (Be-exp) normal controls and sarcoidosis subjects were enrolled. Peripheral blood mononuclear cells (PBMN) were cultured in the presence and absence of beryllium sulfate. Neopterin levels were determined from cell supernatants by enzyme linked immunosorbent assay (ELISA). Clinical evaluation of CBD subjects included chest radiography, pulmonary function testing, exercise testing, and the BeLPT. CBD patients produced higher levels of neopterin in both unstimulated and Be-stimulated conditions compared to all other subjects (P < 0.0001). Unstimulated neopterin mononuclear cell levels overlapped among groups, however, Be-stimulated neopterin levels in CBD showed little overlap. Using a neopterin concentration of 2.5 ng/ml as a cutoff, Be-stimulated neopterin had a sensitivity of 80% and specificity of 100% for CBD and was able to differentiate CBD from BeS. Be-stimulated neopterin was inversely related to measures of pulmonary function, exercise capacity, and gas exchange. Neopterin may be a useful diagnostic adjunct in the non-invasive assessment of CBD, differentiating CBD from BeS. Further studies will be required to determine how it performs in workplace screening. Copyright 2003 Wiley-Liss, Inc.
Werner-Felmayer, G; Werner, E R; Fuchs, D; Hausen, A; Reibnegger, G; Wachter, H
1990-05-15
Determination of neopterin [D-erythro-6-(1',2',3'-trihydroxypropyl)pterin] in body fluids is a powerful diagnostic tool in a variety of diseases in which activation of cellular immune mechanisms is involved, such as certain malignancies, allograft rejection, and autoimmune and infectious diseases. In vitro, neopterin is released into the supernatant by peripheral blood-derived monocytes/macrophages upon stimulation with gamma-interferon. In parallel, cleavage of tryptophan by indoleamine 2,3-dioxygenase is induced. We report here that the human myelomonocytic cell line THP-1 forms neopterin and degrades tryptophan upon treatment with gamma-interferon. Like in macrophages alpha-interferon and beta-interferon induce these pathways only to a much smaller degree. The action of interferons is enhanced by cotreatment with tumor necrosis factor alpha, lipopolysaccharide, or dexamethasone. gamma-Interferon-induced neopterin formation and indoleamine 2,3-dioxygenase activity are increased by raising extracellular tryptophan concentrations. The pattern of intracellularly formed pteridines upon stimulation with gamma-interferon shows the unique characteristics of human monocytes/macrophages. Neopterin, monapterin, and biopterin are produced in a 50:2:1 ratio. Thus, the THP-1 cell line provides a permanent, easily accessible in vitro system for studying the induction and mechanism of neopterin formation.
Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction.
Erkenekli, K; Keskin, U; Uysal, B; Kurt, Y G; Sadir, S; Çayci, T; Ergün, A; Erkaya, S; Danişman, N; Uygur, D
2015-04-01
The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP) concentrations compared with those with uncomplicated pregnancy. A total of 34 pregnant women with FGR and 62 patients with uncomplicated pregnancy were included. Neopterin and CRP levels were measured at the time of diagnosis. The primary outcome of this study was to compare the neopterin and CRP levels in pregnant women with FGR and those with uncomplicated pregnancies. The secondary outcome of our study was to evaluate the correlation between fetal birth weight and maternal neopterin levels. The serum neopterin levels were significantly elevated in pregnant women with FGR (22.71 ± 7.70 vs 19.15 ± 8.32). However, CRP was not elevated in pregnant women with FGR (7.47 ± 7.59 vs 5.29 ± 3.58). These findings support the hypothesis that pregnancy with FGR is associated with a marked increase in macrophage activation and the natural immune system.
Turgut Çankaya, Zeynep; Bodur, Ayşen; Taçoy, Gülten; Ergüder, Imge; Aktuna, Derya; Çengel, Atiye
2018-04-05
The presence of neopterin in gingival crevicular fluid (GCF) is a marker for local and acute immune activation, and the presence of vascular cell adhesion molecule (VCAM-1) in GCF is accepted as a marker for chronic vascular inflammation. This study aimed to evaluate effects of periodontal treatment on GCF levels of neopterin and VCAM-1 in patients with chronic periodontitis (CP) with acute myocardial infarction (AMI) compared with systemically healthy CP patients. Sixty subjects (20 CP patients with AMI, 20 healthy CP patients, and 20 healthy controls) were included. GCF samples were analyzed at baseline and after 3 and 6 months, and the probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing, gingival (GI) and plaque (PI) indices were recorded. We determined neopterin and VCAM-1 levels (concentration and total amount) using enzyme-linked immunosorbent assay (ELISA). No significant differences were seen between the AMI+CP and CP groups for PI, GI, GCF levels of neopterin and VCAM-1 at baseline. The number of teeth with 5 mm≤CAL<7 mm and CAL≥7 mm were significantly increased in the AMI+CP group at baseline. There were no significant differences between the AMI+CP and CP for PI, CAL, GCF volumes, and the AMI+CP group had the highest clinical improvement in the number of teeth with 5 mm≤CAL<7 mm at the sixth month. There were significant positive correlations between clinical periodontal inflammation and the presence of neopterin and VCAM-1 in GCF prior to and following periodontal treatment, and between the GCF volume and clinical parameters. Data suggest that the total amount and concentration of neopterin and VCAM-1 in GCF seemed to be closely associated with periodontal disease severity in CP patients with AMI. Moreover, the results of our study demonstrate that the past periodontal status is potentially correlated between groups, with similar periodontal disease severity.
[Neopterin levels and systemic inflammatory response syndrome in pediatric critically ill patients].
Gil-Gómez, Raquel; Blasco-Alonso, Javier; Sánchez-Yáñez, Pilar; Rosa-Camacho, Vanessa; Milano Manso, Guillermo
2017-12-01
Neopterin and biopterin are sub-products of redox reactions, which act as cofactors of enzymes responsible for nitric oxide production. The hypothesis is presented that plasma neopterin and biopterin evolve differently during the first days in a critically ill child. A single-centre prospective observational study was conducted on patients 7 days to 14 years admitted to our Paediatric Intensive Care Unit (PICU) and that met Systemic inflammatory response syndrome (SIRS) criteria. Neopterin and biopterin levels, as well as other acute phase reactants, were collected at admission and at 24 h. A total of 28 patients were included, of which 78.9% were male, The median age was 5.04 years (interquartile range [IQR] 1.47-10.26), and PRISM II 2.0% (IQR 1.1-5.0). Mechanical ventilation (MV) was used in 90% of patients, with a median duration of 6.0 hrs (IQR 3.7-102.0). The median length of stay in PICU was 5.0 days (IQR 2.7-18.7), maximum VIS mean of 0 (IQR 0-14). Baseline neopterin level was 2.3±1.2 nmol/l and at 24 h it was 2.3±1.4 nmol/l. Baseline biopterin was 1.3±0.5 nmol/l and 1.4±0.4 nmol/l at 24 h. Neopterin levels were significantly higher in patients with PICU length of stay > 6 days (P=.02), patients who needed MV >24 h (P=.023), and those who developed complications (P=.05). Neopterin correlates directly and is statistically significant with the duration of MV (rho=.6, P=.011), PICU length of stay (rho=.75, P<.0001), and VIS (rho=.73, P=.001). Additionally, biopterin directly correlates with the PRISM (rho=.61, P=.008). There is a higher neopterin level when there is a longer PICU stay, higher VIS score, longer time on MV, and occurrence of complications, indicating the involvement of an activation of the cellular immune system. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Activation of cellular immune response in acute pancreatitis.
Mora, A; Pérez-Mateo, M; Viedma, J A; Carballo, F; Sánchez-Payá, J; Liras, G
1997-01-01
BACKGROUND: Inflammatory mediators have recently been implicated as potential markers of severity in acute pancreatitis. AIMS: To determine the value of neopterin and polymorphonuclear (PMN) elastase as markers of activation of cellular immunity and as early predictors of disease severity. PATIENTS: Fifty two non-consecutive patients classified according to their clinical outcome into mild (n = 26) and severe pancreatitis (n = 26). METHODS: Neopterin in serum and the PMN elastase/A1PI complex in plasma were measured during the first three days of hospital stay. RESULTS: Within three days after the onset of acute pancreatitis, PMN elastase was significantly higher in the severe pancreatitis group. Patients with severe disease also showed significantly higher values of neopterin on days 1 and 2 but not on day 3 compared with patients with mild disease. There was a significant correlation between PMN elastase and neopterin values on days 1 and 2. PMN elastase on day 1 predicted disease severity with a sensitivity of 76.7% and a specificity of 91.6%. Neopterin did not surpass PMN elastase in the probability of predicting disease severity. CONCLUSIONS: These data show that activation of cellular immunity is implicated in the pathogenesis of acute pancreatitis and may be a main contributory factor to disease severity. Neopterin was not superior to PMN elastase in the prediction of severity. PMID:9245935
Ilich-Stoianovich, O; Nasonov, E L; Balabanova, R M
2000-01-01
To evaluate effects of low-intensity infrared impulse laser therapy (IRILT) on concentration of immunity activation [not readable: see text] (soluble receptors of TNF-alpha and neopterin) and indicator of the inflammation activity (concentration of C-reactive protein) in patients with rheumatoid arthritis (RA). Enzyme immunoassay, radioimmunoassay, enzyme immunoassay and radial immunodiffusion were used to measure soluble receptors of TNF-alpha, neopterin and C-reactive protein in 38 females with verified RA receiving IRILT or sham procedures. IRILT induced lowering of neopterin, TNF-alpha soluble receptors (p < 0.01) and C-reactive protein (p < 0.01). The findings give pathogenetical grounds for IRILT use in RA as this treatment suppresses functional activity of macrophages which serve the main source of neopterin and the receptors synthesis.
Role of IL-6 and neopterin in the pathogenesis of herpetic encephalitis.
Bociąga-Jasik, Monika; Cieśla, Andrzej; Kalinowska-Nowak, Anna; Skwara, Paweł; Garlicki, Aleksander; Mach, Tomasz
2011-01-01
Herpetic encephalitis (HSE) is one of the most severe infection of the central nervous system (CNS), connected with high mortality rate, even when appropriate therapy has been introduced. Better understanding of pathomechanisms responsible for neuronal injury during the course of the disease can be useful in the assessment of the risk of the occurrence of severe complications, as well as in potential introduction of additional therapeutic methods. The purpose of this study is to assess the correlation between concentration of neopterin and IL-6 in the CSF and serum, and the course of HSE. In this study, 36 patients with HSE were investigated, and the control group consisted of 32 patients in whom the infection of the CNS was excluded. We observed significantly higher concentration of neopterin and IL-6 in the CSF of patients with HSV as compared with the control group. Neopterin and IL-6 levels in the CSF correlated with the course of HSE. Higher values were connected with the risk of respiratory failure, development of permanent neurologic complications and patient death. Negative correlations between concentration of IL-6 and neopterin and patient condition assessed by Glasgow Coma Scale (GCS) were observed. Neopterin with high sensitivity and specificity allowed to predict the risk of death or severe neurological complications. Increased concentration of neopterin and IL-6 in the CSF and serum revealed reciprocal positive correlation. Assessment of the concentration of IL-6 and neopterin in the serum was not useful to predict the course of HSE.
Dusek, Tomas; Orhalmi, Julius; Sotona, Otakar; Krcmova, Lenka Kujovska; Javorska, Lenka; Dolejs, Josef; Paral, Jiri
2018-03-01
At present, there are no strong predictors, nor a useful scoring system, that clearly identifies patients at risk for anastomotic leakage. This study aimed to investigate a new method that assesses this risk by monitoring levels of neopterin, tryptophan, and kynurenine, in bodily fluids. This prospective study included patients who underwent elective rectal resection for carcinoma. The basic condition for inclusion was rectal anastomosis using the double-stapling technique. Preoperative levels of neopterin, tryptophan, kynurenine, and their ratios, were assessed with blood and urine samples. These levels were then monitored for 6 postoperative days in venous blood, urine, and abdominal drainage fluid. A total of 42 patients were enrolled in the study. Thirty-six patients underwent a laparoscopic resection and 6 patients had an open procedure. No differences were found among neopterin, tryptophan, and kynurenine serum levels. However, the groups were observed to have significant differences in the urinary neopterin/creatinine ratio: the preoperative neopterin/creatinine ratio was 139.5 μmol/mol in the group with leakage, vs 114.8 μmol/mol in the group without complications, p = 0.037. The same results were observed during the postoperative period, p = 0.012. Additionally, the group with complications had a higher mean value of neopterin in drainage fluid, p = 0.048. Our study demonstrated that high preoperative levels of urinary neopterin could be interpreted as a risk for anastomotic leakage. Moreover, pathological levels of neopterin in urine and abdominal drainage fluid could be useful for early identification of anastomotic leakage during the postoperative period prior to its clinical development.
New Markers of Inflammation and Tubular Damage in Children with Chronic Kidney Disease.
Musiał, Kinga; Bargenda, Agnieszka; Drożdż, Dorota; Zwolińska, Danuta
2017-01-01
Monocyte chemoattractant protein- (MCP-) 1, macrophage colony-stimulating factor (MCSF), and neopterin are connected with monocyte migration and transition into macrophages, leading to fibrosis and tubular damage in the course of CKD. The aim of the study was to analyze the applicability of urinary fractional excretion (FE) of MCP1, MCSF, and neopterin, as markers of inflammation and tubular damage, in children with CKD. The study group consisted of 61 children with CKD stages 1-5 and 23 age-matched controls. The serum and urine concentrations of MCP1, MCSF, and neopterin were assessed by ELISA and then the fractional excretion (FE) was calculated. FE MCSF and neopterin values exceeded 1% already in controls. FE MCSF rose significantly since CKD stages 1-2, FE neopterin since CKD stages 3-5. FE MCP1 was below 1% in healthy controls and in CKD stages 1-2, then increased significantly in CKD stages 3-5. The FE MCP-1 values show that inflammation precedes the tubular dysfunction. FE MCSF and FE neopterin may be considered new markers of the renal parenchyma progressive damage. Fractional excretion may become a useful tool in the assessment of inflammation and tubular damage in children with CKD.
Pingle, Shubhangi K.; Thakkar, Lucky R.; Jawade, Aruna A.; Tumane, Rajani G.; Jain, Ruchika K.; Soni, Pravin N.
2015-01-01
Introduction: Bauxite ore is a major source of aluminum (Al) which contains approximately 35–60% Al by weight. Occupational and environmental bauxite dust exposure may cause toxicity by interaction with human biological systems resulting in oxidative stress (OS) and cell death. A neopterin derivative as an antioxidant is able to modulate cytotoxicity by the induction of OS. Materials and Methods: A total of 273 subjects were selected for blood collection from three different major Al producing bauxite mines and were categorized into three groups as experimental (Exp) (n = 150), experimental controls (ExC) (n = 73) and control (Con) (n = 50). Whole blood and serum samples were used for measurement of Al, neopterin, urea and creatinine values. Statistical analysis was performed using R-2.15.1 programming language. Results and Discussion: The result showed that age, body mass index and the behavioral habits, that is, smoking, tobacco and alcohol consumption have possible effects on neopterin level. Serum neopterin levels were found to be significantly higher (P <0.0001) in the experimental group as compared to other groups. Significantly positive correlation (P < 0.0001) was observed between neopterin and creatinine. It was also observed that neopterin level increases as the duration of exposure increases. Conclusion: On the basis of findings it was concluded that exposure to bauxite dust (even at low levels of Al) changes biochemical profile leading to high levels of serum neopterin. Levels of serum neopterin in workers exposed to bauxite dust were probably examined for the 1st time in India. The outcome of this study suggested that serum neopterin may be used as potential biomarker for early detection of health risks associated with bauxite dust exposed population. PMID:26500413
Weimer, R; Süsal, C; Yildiz, S; Staak, A; Pelzl, S; Renner, F; Dietrich, H; Daniel, V; Kamali-Ernst, S; Ernst, W; Padberg, W; Opelz, G
2006-08-01
Immunological monitoring for chronic allograft nephropathy (CAN) is of great potential interest. We assessed serum soluble CD30 (sCD30) together with in vitro Th2-type responses (IL-4, IL-10, CD4 helper activity) and neopterin in a prospective study of 84 renal transplant recipients with 2-year follow-up. Patients were randomized to CsA/Aza, CsA/MMF and Tacr/Aza, respectively, to analyze the effect of immunosuppression on posttransplant sCD30 and neopterin. ATG induction and acute rejections did not alter sCD30 levels whereas CMV disease was associated with transient upregulation of sCD30 (p = 0.003 at 4 months) and sustained upregulation of neopterin (corrected for graft function (Neo/CR) p = 0.005 at 2 years). Tacr versus CsA treatment proved to be an independent variable associated with downregulation of 1-year sCD30, which was positively related to Neo/CR (p = 0.007 and 0.01, respectively; logistic regression). Importantly, increased 1-year sCD30 and Neo/CR were associated with decreased glomerular filtration rate at 2 years (p = 0.02 and p < 0.0005, respectively) and evidence of CAN (p < 0.0005). High 1-year sCD30 could not be attributed to enhanced Th2-type responses and was not associated with HLA antibody formation. Our data suggest that elevated sCD30 and neopterin predict graft deterioration by CAN. Tacr effectively downregulates these responses and might be of advantage in patients with elevated sCD30 or neopterin.
[Monitoring of neopterin and INF-gamma in children with recurrent respiratory tract infection].
Shervashidze, M R; Barabadze, K A; Vekua, M V; Akhvlediani, I K
2006-07-01
The upper and lover respiratory tract infections are usually mild and self-limited. Owing to their frequency recurrent upper and lower respiratory tract infection in children and adults constitute a major global health problem. The goal of our study was to observe 30 children with recurrent respiratory tract infection, 17 boy and 13 girl, they were treated with Ribomunyl. The control group consisted of 15 children who received only basic therapy (10 boys and 5 girls). The age of the children ranged between 8 months and 6 years. The study was conducted by the simply randomization method. Clinical and laboratory examinations were evaluated before and after treatment. The concentration of INF-gamma was rather low in study group in comparison with control group before the beginning of the treatment, that indicates insufficient stimulation of T-lymphocytes in children with recurrent infection. INF-gamma lever significantly increased after treatment (Statistically significantly P<0.05) in study group in comparison with control group. Neopterin level unlike INF-gamma in study group was higher than in the control group, before and after treatment. This fact can be explained that neopterin as a slowly acting biologically active substance remains high during the presence of recurrent infections. Ribomunyl treatment significantly increased the level of neopterin. The efficacy of the product is primarily confirmed by significant reductions in the number of recurrent infections episodes and the use of antibacterials. Combined immunostimulating effect of Ribomunyl makes it possible to use Ribomunyl to create a longterm postvaccinal protection of the child.
Maes, Michael; Twisk, Frank N M; Kubera, Marta; Ringel, Karl
2012-02-01
There is evidence that inflammatory pathways and cell-mediated immunity (CMI) play an important role in the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Activation of inflammatory and CMI pathways, including increased levels of cytokines, is known to induce fatigue and somatic symptoms. Given the broad spectrum inflammatory state in ME/CFS, the aim of this study was to examine whether inflammatory and CMI biomarkers are increased in individuals with ME/CFS. In this study we therefore measured plasma interleukin-(IL)1, tumor necrosis factor (TNF)α, and PMN-elastase, and serum neopterin and lysozyme in 107 patients with ME/CFS, 37 patients with chronic fatigue (CF), and 20 normal controls. The severity of ME/CFS was measured with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. Serum IL-1, TNFα, neopterin and lysozyme are significantly higher in patients with ME/CFS than in controls and CF patients. Plasma PMN-elastase is significantly higher in patients with ME/CFS than in controls and CF patients and higher in the latter than in controls. Increased IL-1 and TNFα are significantly correlated with fatigue, sadness, autonomic symptoms, and a flu-like malaise; neopterin is correlated with fatigue, autonomic symptoms, and a flu-like malaise; and increased PMN-elastase is correlated with concentration difficulties, failing memory and a subjective experience of infection. The findings show that ME/CFS is characterized by low-grade inflammation and activation of CMI. The results suggest that characteristic symptoms of ME/CFS, such as fatigue, autonomic symptoms and a flu-like malaise, may be caused by inflammatory mediators, e.g. IL-1 and TNFα. Copyright © 2011 Elsevier B.V. All rights reserved.
Malakaneh, M; Rasaee, M J; Rahbarizadeh, F; Madani, R; Forozandeh, M M; Khabiri, K; Alimohammadian, M H
2001-04-01
An active ester derivative of neopterin was prepared using 4-(N-maleimidomethyl) cyclohexan 4-carboxilic acid N-hydroxy succinimide ester (MCH-NHS), conjugated to bovine serum albumin (BSA) and injected for antibody production (for both monoclonal and polyclonal antibodies). High titer antibody producing spleen cells were removed and fused with myeloma cells of Sp2/0 origin. Neopterin was conjugated to the enzyme penicillinase by a one-step glutaraldehyde method, which was used as tracer. A novel enzyme immunoassay was developed using this conjugate to screen and characterize the monoclonal antibody (MAb) produced in these experiments. After limiting dilutions, it was found that antibody produced by one clone with a Ka value of 7.6 x 10-7 mol/L was specific for a number of structurally related molecules. This clone was found to be of IgG class and IgG2a subclass. The standard curvewas constructed with a sensitivity of 10 pg/well (100 pg/mL) covering up to 1 ng/mL.
Yan, Jin-quan; Tan, Chun-zhi; Wu, Jin-hua; Zhang, Dong-cui; Chen, Ji-ling; Zeng, Bin-yuan; Jiang, Yu-ping; Nie, Jin; Liu, Wei; Liu, Qin; Dai, Hao
2013-07-01
To investigate the effects of neopterin on ABCA1 expression and cholesterol efflux in human THP-1 macrophage-derived foam cells, and to explore the role of the liver X receptor alpha (LXRα) involved. In the present study, THP-1 cells were pre-incubated with ox-LDL to become foam cells. The protein and mRNA expression were examined by Western blot assays and real-time quantitative PCR, respectively. Liquid scintillation counting and high performance liquid chromatography assays were used to test cellular cholesterol efflux and cholesterol content. Neopterin decreased ABCA1 expression and cholesterol efflux in a time- and concentration-dependent manner in THP-1 macrophage-derived foam cells, and the LXRα siRNA can reverse the inhibitory effects induced by neopterin. Neoterin has a negative regulation on ABCA1 expression via the LXRα signaling pathway, which suggests the aggravated effects of neopterin on atherosclerosis.
Werner-Felmayer, G; Baier-Bitterlich, G; Fuchs, D; Hausen, A; Murr, C; Reibnegger, G; Werner, E R; Wachter, H
1995-01-01
In a number of mammalian cell types, pteridine biosynthesis from guanosine 5'-triphosphate and formation of nitric oxide from L-arginine are induced by gamma interferon (IFN-gamma) and bacterial lipopolysaccharide (LPS). We assessed the possibility of using such metabolic alterations for the in vitro detection of pyrogens. Products from gram-negative and gram-positive bacteria and related synthetic compounds were tested for their potential to induce either of these pathways. Stimulation of pteridine biosynthesis was monitored as the formation of neopterin in the human myelomonocytic cell line THP-1. The formation of nitric oxide was determined as nitrite in murine J774A.1 macrophage cultures. The substances tested included toxic and detoxified parts of LPS and lipid A from Escherichia coli, Salmonella typhimurium, Salmonella minnesota, and Klebsiella pneumoniae as well as lipoteichoic acid and toxic shock syndrome toxin 1 from Staphylococcus aureus. Furthermore, two cell wall compounds from Mycobacterium tuberculosis, trehalose 6,6'-dimycolate and N-acetylmuramyl-L-alanyl-D-isoglutamine, which are active components of Freund's adjuvant, were used. When applied as a single stimulus, only the whole LPS molecule potently stimulated neopterin or nitrite formation. Lipid A and products from gram-positive bacteria were weakly active. For neopterin formation, lipid A required the presence of fetal calf serum. Besides detoxified LPS and independently from the presence of serum, all bacterial compounds tested strongly increased the effects mediated by IFN-gamma. Our results show that bacterial pyrogens can be detected by monitoring the formation of neopterin or nitrite. This may provide a basis for the development of an in vitro assay for the detection of pyrogenic contamination with the aim of replacing the currently used animal test. PMID:7664177
Chen, Der-Yuan; Chen, Hsin-Hua; Hsieh, Chia-Wei; Yeh, Yea-Wen; Lan, Joung-Liang
2016-01-01
QuantiFERON-TB-Gold (QFT-G) conversion is frequently observed in rheumatoid arthritis (RA) patients receiving biologic therapy. However, there have not been any known biomarkers available for detecting tuberculosis (TB) in QFT-G converters. We aimed to evaluate clinical utility of cytokines/chemokines for detecting TB in patients with QFT-G conversion. Among a total of 227 RA patients who underwent QFT-G assay, 187 QFT-G-negative patients received biologic therapy without isoniazid prophylaxis. QFT-G assay was repeated at week 52 of biologic therapy or at the time of TB diagnosis. Levels of cytokines/chemokines were determined by magnetic bead array or ELISA in QFT-G converters and 12 non-RA patients with TB (non-RA TB). QFT-G conversion was found in 54 (28.9%) of 187 baseline QFT-G-negative patients, of which 7 (13.0%) developed active TB during the one-year follow-up period. Among the examined cytokines/chemokines, non-stimulated and TB-antigen-stimulated neopterin levels were significantly higher in RA patients who developed TB (RA-TB) (median, 24.5pg/ml and 23053pg/ml, respectively) and non-RA TB patients (12.2pg/ml and 9633pg/ml, respectively) compared with QFT-G converters without TB (3.0pg/ml and 2720pg/ml, respectively, both p<0.001). Rising levels of neopterin relative to baseline (non-stimulated levels, 4.4pg/ml vs. 24.5pg/ml; TB-antigen-stimulated levels, 1801pg/ml vs. 23053pg/ml) were observed in QFT-G converters who developed TB. A high proportion (85.7%) of QFT-G converters with high plasma neopterin levels developed TB during the one-year follow-up period. In conclusion, RA patients with QFT-G conversion during the period of biologic therapy should be carefully monitored for elevation of neopterin levels, which is associated with TB risk in QFT-G converters, particularly in TB-endemic areas. PMID:27861525
Theofylaktopoulou, Despoina; Ulvik, Arve; Midttun, Øivind; Ueland, Per Magne; Vollset, Stein Emil; Nygård, Ottar; Hustad, Steinar; Tell, Grethe S; Eussen, Simone J P M
2014-10-14
Vitamins B2 and B6 are cofactors in the kynurenine pathway. Many of the kynurenines are neuroactive compounds with immunomodulatory effects. In the present study, we aimed to investigate plasma concentrations of vitamins B2 and B6 as determinants of kynurenines and two markers of interferon-γ-mediated immune activation (kynurenine:tryptophan ratio (KTR) and neopterin). We measured the concentrations of vitamins B2 and B6 vitamers, neopterin, tryptophan and six kynurenines (i.e. kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid) in plasma from 7051 individuals. Dietary intake of vitamins B2 and B6 was assessed using a validated FFQ. Associations were investigated using partial Spearman's correlations, generalised additive models, and segmented or multiple linear regression. The B2 vitamer, riboflavin, was positively associated with 3-hydroxyanthranilic acid and xanthurenic acid, with correlation coefficients, as obtained by segmented regression, of 0·20 (95 % CI 0·16, 0·23) and 0·24 (95 % CI 0·19, 0·28), at riboflavin concentrations below the median value (13·0 nmol/l). The vitamin B6 vitamer, pyridoxal 5'-phosphate (PLP), was positively associated with most kynurenines at PLP concentrations < 39·3-47·0 nmol/l, and inversely associated with 3-hydroxykynurenine with the association being more prominent at PLP concentrations < 18·9 nmol/l. Riboflavin and PLP were associated with xanthurenic acid only at relatively low, but normal concentrations of both vitamers. Lastly, PLP was negatively correlated with neopterin and KTR. These results demonstrate the significant and complex determination of kynurenine metabolism by vitamin status. Future studies on B-vitamins and kynurenines in relation to chronic diseases should therefore integrate data on relevant biomarkers related to B-vitamins status and tryptophan metabolism.
te Witt, René; van Wolfswinkel, Marlies E; Petit, Pieter L; van Hellemond, Jaap J; Koelewijn, Rob; van Belkum, Alex; van Genderen, Perry J J
2010-09-14
Most clinicians in developed, non-malaria endemic countries have limited or no experience in making clinical assessments of malaria disease severity and subsequent decisions regarding the need for parenteral therapy or high-level monitoring in febrile patients with imported malaria. In the present study, the diagnostic accuracy of plasma soluble Triggering Receptor Expressed on Myeloid cells 1 (TREM-1), neopterin and procalcitonin levels as biomarkers for severe Plasmodium falciparum disease was evaluated in 104 travellers with imported malaria (26 patients with non-P. falciparum malaria, 64 patients with uncomplicated P. falciparum malaria and 14 patients with severe P. falciparum malaria). TREM-1, neopterin and procalcitonin were determined in serum using commercially available ELISA or EIA tests. The diagnostic performance of these biomarkers for severe disease was compared with plasma lactate, a well-validated parameter for disease severity in patients with malaria, as reference. Severe malaria was defined according to the modified WHO criteria. No significant differences in TREM-1 levels were detected between the different patient groups. Patients with severe P. falciparum malaria had significantly higher neopterin and procalcitonin levels on admission when compared to patients with uncomplicated P. falciparum malaria or non-P. falciparum malaria. Receiver Operating Characteristic (ROC) curve analysis showed that neopterin had the highest Area-Under-the-ROC curve (AUROC 0.85) compared with plasma lactate (AUROC 0.80) and procalcitonin (AUROC 0.78). At a cut-off point of 10.0 ng/ml, neopterin had a positive and negative predictive value of 0.38 and 0.98 whereas procalcitonin, at a cut-off point of 0.9 ng/ml, had a positive and negative predictive value of 0.30 and 1.00. Although the diagnostic value of neopterin and procalcitonin is limited, the high negative predictive value of both neopterin and procalcitonin may be helpful for a rapid exclusion of severe
Jespersen, Sofie; Pedersen, Karin Kæreby; Anesten, Birgitta; Zetterberg, Henrik; Fuchs, Dietmar; Gisslén, Magnus; Hagberg, Lars; Trøseid, Marius; Nielsen, Susanne Dam
2016-04-21
HIV-associated cognitive impairment has declined since the introduction of combination antiretroviral treatment (cART). However, milder forms of cognitive impairment persist. Inflammation in the cerebrospinal fluid (CSF) has been associated with cognitive impairment, and CSF neurofilament light chain protein (NFL) and CSF neopterin concentrations are increased in those patients. Microbial translocation in HIV infection has been suggested to contribute to chronic inflammation, and lipopolysaccharide (LPS) and soluble CD14 (sCD14) are markers of microbial translocation and the resulting monocyte activation, respectively. We hypothesised that microbial translocation contributes to inflammation and axonal damage in the central nervous system (CNS) in untreated HIV infection. We analyzed paired samples of plasma and CSF from 62 HIV-infected, untreated patients without cognitive symptoms from Sahlgrenska University Hospital, Gothenburg, Sweden. Measurements of neopterin and NFL in CSF were available from previous studies. Plasma and CSF sCD14 was measured using ELISA (R&D, Minneapolis, MN), and plasma and CSF LPS was measured using LAL colorimetric assay (Lonza, Walkersville, MD, USA). Univariate and multivariate regression analyses were performed. LPS in plasma was associated with plasma sCD14 (r = 0.31, P = 0.015), and plasma sCD14 was associated with CSF sCD14 (r = 0.32, P = 0.012). Furthermore, CSF sCD14 was associated with NFL (r = 0.32, P = 0.031) and neopterin (r = 0.32, P = 0.012) in CSF. LPS was not detectable in CSF. In a multivariate regression model CSF sCD14 remained associated with NFL and neopterin after adjusting for age, CD4+ cell count, and HIV RNA in CSF. In a group of untreated, HIV-infected patients LPS was associated with sCD14 in plasma, and plasma sCD14 was associated CSF sCD14. CSF sCD14 were associated with markers of CNS inflammation and axonal damage. This suggest that microbial translocation might be a driver
Abdel-Haq, Ayman; Kusnierz-Cabala, Beata; Darczuk, Dagmara; Sobuta, Eliza; Dumnicka, Paulina; Wojas-Pelc, Anna; Chomyszyn-Gajewska, Maria
2014-11-01
Lichen planus together with its oral variant is a chronic, inflammatory disease of the skin and the mucosa of unclear aetiology and with an unpredictable course that still poses a major problem in terms of diagnosis and treatment. The objective of this study was to assess the concentrations of interleukin-6 (IL-6) and neopterin in saliva and serum of patients with lichen planus (including reticular and erosive form of oral lichen planus) and to compare them with the concentrations observed in healthy controls. The study material comprised serum and saliva samples from 56 patients diagnosed with lichen planus and 56 healthy volunteers. The ELISA test was used to measure concentrations of IL-6 and neopterin in the serum and saliva of the study participants. The concentrations of IL-6 in saliva and serum of patients with lichen planus were significantly higher than in controls (P = 0.0002; P < 0.0001). The difference remains significant after adjustment for gingivitis and age. Patients with atrophic-erosive oral lichen planus had significantly higher IL-6 concentrations in their saliva compared to patients with reticular form of disease (P = 0.01). The concentrations of neopterin were significantly higher in the serum but not in saliva of lichen planus patients vs. controls (P <0.0001). Serum levels of proinflammatory cytokines IL-6 and neopterin are increased in lichen planus as well as the salivary concentrations of IL-6. The differences observed in IL-6 levels in patients with erosive-atrophic forms of oral lichen planus may indicate a substantial role played by the cytokine in the disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Martin, Genevieve E; Gouillou, Maelenn; Hearps, Anna C; Angelovich, Thomas A; Cheng, Allen C; Lynch, Fiona; Cheng, Wan-Jung; Paukovics, Geza; Palmer, Clovis S; Novak, Richard M; Jaworowski, Anthony; Landay, Alan L; Crowe, Suzanne M
2013-01-01
Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.
Suh, Joome; Sinclair, Elizabeth; Peterson, Julia; Lee, Evelyn; Kyriakides, Tassos C; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Price, Richard W; Gisslen, Magnus; Spudich, Serena
2014-12-03
Central nervous system (CNS) inflammation is a mediator of brain injury in HIV infection. To study the natural course of CNS inflammation in the early phase of infection, we analyzed longitudinal levels of soluble and cellular markers of inflammation in cerebrospinal fluid (CSF) and blood, beginning with primary HIV-1 infection (PHI). Antiretroviral-naïve subjects identified as having PHI (less than one year since HIV transmission) participated in phlebotomy and lumbar puncture at baseline and at variable intervals thereafter. Mixed-effects models were used to analyze longitudinal levels of CSF neopterin and percentages of activated cluster of differentiation (CD)4+ and CD8+ T-cells (co-expressing CD38 and human leukocyte antigen-D-related (HLA-DR)) in blood and CSF. A total of 81 subjects were enrolled at an average of 100 days after HIV transmission and had an average follow-up period of 321 days, with the number of visits ranging from one to 13. At baseline, the majority of subjects had CSF neopterin concentrations above the upper limit of normal. The baseline concentration was associated with the longitudinal trajectory of CSF neopterin. In subjects with baseline levels of less than 21 nmol/L, a cutoff value obtained from a mixed-effects model, CSF neopterin increased by 2.9% per 10 weeks (n = 33; P <0.001), whereas it decreased by 6.7% in subjects with baseline levels of more than 21 nmol/L (n = 11; P = 0.001). In a subset with available flow cytometry data (n = 42), the percentages of activated CD4+ and CD8+ T-cells in CSF increased by 0.8 (P <0.001) and 0.73 (P = 0.02) per 10 weeks, respectively. Neopterin levels and the percentages of activated CD4+ and CD8+ T-cells in CSF progressively increase in most subjects without treatment during early HIV-1 infection, suggesting an accrual of intrathecal inflammation, a major contributor to neuropathology in HIV infection.
Hellmuth, Joanna; Colby, Donn; Valcour, Victor; Suttichom, Duanghathai; Spudich, Serena; Ananworanich, Jintanat; Prueksakaew, Peeriya; Sailasuta, Napapon; Allen, Isabel; Jagodzinski, Linda L; Slike, Bonnie; Ochi, Derek; Paul, Robert
2017-11-01
This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm 3 , t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann-Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.
Singer, Magdalena; Burbaum, Christina; Fritzsche, Kurt; Peterlini, Sylvia; Bliem, Harald R; Ocaña-Peinado, Francisco M; Fuchs, Dietmar; Schubert, Christian
2017-01-01
This study on a breast cancer survivor suffering from cancer-related fatigue (CaRF) and depression investigated the bidirectional relationship between cellular immune activity and subjective sleep. The 49-year-old patient (breast cancer diagnosis 5 years before the study, currently in remission) collected her full urine output for 28 days in 12-h intervals (8:00 p.m. to 8:00 a.m. and 8:00 a.m. to 8:00 p.m.). These urine samples were used to determine urinary neopterin (cellular immune activation marker) and creatinine concentrations via high-pressure liquid chromatography (HPLC). Each morning, the patient answered questions on five sleep variables: sleep quality (SQ), sleep recreational value (SRV), total sleep time (TST), total wake time (TWT), and awakenings during sleep period (ADS). For the purpose of this study, the time series of the nighttime urinary neopterin levels and the five sleep variables were determined. Using centered moving average (CMA) smoothing and cross-correlational analysis, this study showed that increases in the positive sleep variables SQ and SRV were followed by urinary neopterin concentration decreases after 96-120 h (SQ, lag 4: r = -0.411; p = 0.044; SRV: lag 4: r = -0.472; p = 0.021) and 120-144 h (SRV, lag 5: r = -0.464; p = 0.026). Increases in the negative sleep variable TWT, by contrast, were followed by increases in urinary neopterin concentrations 72-96 h later (lag 3: r = 0.522; p = 0.009). No systematic effects in the other direction, i.e., from urinary neopterin levels to sleep, were observed in this study. Although preliminary, the findings of this study highlight the benefit of carefully investigating temporal delays and directions of effects when studying the dynamic relationship between sleep and immune variables in the natural context of everyday life.
Shah, Nishel Mohan; Herasimtschuk, Anna A.; Boasso, Adriano; Benlahrech, Adel; Fuchs, Dietmar; Imami, Nesrina; Johnson, Mark R.
2017-01-01
During pregnancy, the mother allows the immunologically distinct fetoplacental unit to develop and grow. Opinions are divided as to whether this represents a state of fetal-specific tolerance or of a generalized suppression of the maternal immune system. We hypothesized that antigen-specific T cell responses are modulated by an inhibitory T cell phenotype and modified dendritic cell (DC) phenotype in a gestation-dependent manner. We analyzed changes in surface markers of peripheral blood T cells, ex vivo antigen-specific T cell responses, indoleamine 2,3-dioxygenase (IDO) activity (kynurenine/tryptophan ratio, KTR), plasma neopterin concentration, and the in vitro expression of progesterone-induced blocking factor (PIBF) in response to peripheral blood mononuclear cell culture with progesterone. We found that mid gestation is characterized by reduced antigen-specific T cell responses associated with (1) predominance of effector memory over other T cell subsets; (2) upregulation of inhibitory markers (programmed death ligand 1); (3) heightened response to progesterone (PIBF); and (4) reduced proportions of myeloid DC and concurrent IDO activity (KTR). Conversely, antigen-specific T cell responses normalized in late pregnancy and were associated with increased markers of T cell activation (CD38, neopterin). However, these changes occur with a simultaneous upregulation of immune suppressive mechanisms including apoptosis (CD95), coinhibition (TIM-3), and immune regulation (IL-10) through the course of pregnancy. Together, our data suggest that immune tolerance dominates in the second trimester and that it is gradually reversed in the third trimester in association with immune activation as the end of pregnancy approaches. PMID:28966619
Repetitive cryotherapy attenuates the in vitro and in vivo mononuclear cell activation response.
Lindsay, Angus; Othman, Mohd Izani; Prebble, Hannah; Davies, Sian; Gieseg, Steven P
2016-07-01
What is the central question of this study? Acute and repetitive cryotherapy are routinely used to accelerate postexercise recovery, although the effect on resident immune cells and repetitive exposure has largely been unexplored and neglected. What is the main finding and its importance? Using blood-derived mononuclear cells and semi-professional mixed martial artists, we show that acute and repetitive cryotherapy reduces the in vitro and in vivo T-cell and monocyte activation response whilst remaining independent of the physical performance of elite athletes. We investigated the effect of repetitive cryotherapy on the in vitro (cold exposure) and in vivo (cold water immersion) activation of blood-derived mononuclear cells following high-intensity exercise. Single and repeated cold exposure (5°C) of a mixed cell culture (T cells and monocytes) was investigated using in vitro tissue culture experimentation for total neopterin production (neopterin plus 7,8-dihydroneopterin). Fourteen elite mixed martial art fighters were also randomly assigned to either a cold water immersion (15 min at 10°C) or passive recovery protocol, which they completed three times per week during a 6 week training camp. Urine was collected and analysed for neopterin and total neopterin three times per week, and perceived soreness, fatigue, physical performance (broad jump, push-ups and pull-ups) and training performance were also assessed. Single and repetitive cold exposure significantly (P < 0.001) reduced total neopterin production from the mixed cell culture, whereas cold water immersion significantly (P < 0.05) attenuated urinary neopterin and total neopterin during the training camp without having any effect on physical performance parameters. Soreness and fatigue showed little variation between the groups, whereas training session performance was significantly (P < 0.05) elevated in the cold water immersion group. The data suggest that acute and repetitive cryotherapy
Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F
1999-04-01
Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P < 0.01] was noted in levels of total cholesterol, and a decrease of 1.70 mmol/l [1.52-2.30 (28%); P < 0.01] in levels of low-density lipoprotein cholesterol. Plasma levels of fibrinogen had increased [from 4.81 g/l (4.26-5.27) to 5.17 g/l (4.81-5.67); P < 0.05], whereas no significant changes had occurred in intraplatelet levels of cGMP [decrease by 0.05 pmol/10(9) platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/10(9) platelets (-0.37 to 0.86); NS], plasma endothelin-1 [decrease by 0.05 pg/ml (-0.60 to 0.70); NS], plasma factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.
Karu, Naama; McKercher, Charlotte; Nichols, David S; Davies, Noel; Shellie, Robert A; Hilder, Emily F; Jose, Matthew D
2016-11-10
Adults with chronic kidney disease (CKD) exhibit alterations in tryptophan metabolism, mainly via the kynurenine pathway, due to higher enzymatic activity induced mainly by inflammation. Indoles produced by gut-microflora are another group of tryptophan metabolites related to inflammation and conditions accompanying CKD. Disruptions in tryptophan metabolism have been associated with various neurological and psychological disorders. A high proportion of CKD patients self-report symptoms of depression and/or anxiety and decline in cognitive functioning. This pilot study examines tryptophan metabolism in CKD and explores associations with psychological and cognitive functioning. Twenty-seven adults with CKD were part of 49 patients recruited to participate in a prospective pilot study, initially with an eGFR of 15-29 mL/min/1.73 m 2 . Only participants with viable blood samples and complete psychological/cognitive data at a 2-year follow-up were included in the reported cross-sectional study. Serum samples were analysed by Liquid Chromatography coupled to Mass Spectrometry, for tryptophan, ten of its metabolites, the inflammation marker neopterin and the hypothalamic-pituitary-adrenal (HPA) axis marker cortisol. The tryptophan breakdown index (kynurenine / tryptophan) correlated with neopterin (Pearson R = 0.51 P = 0.006) but not with cortisol. Neopterin levels also correlated with indoxyl sulfate (R = 0.68, P < 0.0001) and 5 metabolites of tryptophan (R range 0.5-0.7, all P ≤ 0.01), which were all negatively related to eGFR (P < 0.05). Higher levels of kynurenic acid were associated with lower cognitive functioning (Spearman R = -0.39, P < 0.05), while indole-3 acetic acid (IAA) was correlated with anxiety and depression (R = 0.52 and P = 0.005, R = 0.39 and P < 0.05, respectively). The results of this preliminary study suggest the involvement of inflammation in tryptophan breakdown via the kynurenine pathway, yet
Tarokhian, Hanieh; Taghadosi, Mahdi; Rafatpanah, Hushang; Rajaei, Taraneh; Azarpazhooh, Mahmoud Reza; Valizadeh, Narges; Rezaee, S A Rahim
2017-01-15
Previous studies have suggested debatable roles of Tax and HBZ gene expression in the pathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this study, HTLV-1 and host interactions in the manifestation of HAM/TSP were evaluated. A cross-sectional study was conducted on 33 HAM/TSP patients and 38 HTLV-1 asymptomatic carriers (ACs). HTLV-1-Tax, HBZ gene expression, and proviral load (PVL) were assessed using the quantitative real-time PCR (TaqMan), host plasma neopterin level, and HLA-I, and the clinical manifestation were evaluated. The HTLV-1 PVLs in HAM/TSP and ACs were 306±360.741 copies/10 4 PBMCs and 250.98±629.94 copies/10 4 PBMCs, respectively; the PVL was higher in HAM/TSP than that in ACs (p=0.004). HTLV-1 Tax and HBZ expression in HAM/TSP was higher than that in ACs, wherein only the Tax expression was statistically significant (p=0.039). In contrast to Japanese HTLV-1-infected subjects, HLA-A*02, HLA-A*24, HLA-Cw*08, and HLA-B*5401 did not exhibit preventive effects for HAM/TSP manifestation. The plasma neopterin level was significantly higher in HAM/TSPs than that in ACs; furthermore, there was a strong significant correlation between plasma neopterin and PVL (R=0.76, p=0.001). Moreover, there were significant correlation between urinary disturbances and haematological indices, including the RBC count (R=-0.61, p=0.01) and Hematocrit (Ht) index (R=-0.75, p=0.002), and between mobility disturbances with Tax expression (R=-0.58, p=0.02) and WBC counts (R=-0.54, p=0.04), and finally, a significant association was found between the sensory disturbances and PVL (p=0.05). Overall, HTLV-1 PVL and Tax may be the valid predictors of disease development, and the neopterin level may be a valid predictor of disease progression. In addition, Tax and neopterin are more helpful than PVL for the monitoring of HTLV-1-infected patients. Copyright © 2016 Elsevier B.V. All rights reserved.
Lindsay, Angus; Schmiechen, Alexandra; Chamberlain, Christopher M; Ervasti, James M; Lowe, Dawn A
2018-05-23
Macrophage infiltration is a hallmark of dystrophin-deficient muscle. We tested the hypothesis that Duchenne muscular dystrophy (DMD) patients would have elevated levels of the macrophage synthesized pterins, neopterin and 7,8-dihydroneopterin compared to unaffected age-matched controls. Urinary neopterin/creatinine and 7,8-dihydroneopterin/creatinine were elevated in DMD patients and 7,8-dihydroneopterin/creatinine was associated with patient age and ambulation. 7,8-dihydroneopterin correction with specific gravity was also elevated in DMD patients. Because 7,8-dihydroneopterin is an antioxidant, we then identified a potential role for 7,8-dihydroneopterin in disease pathology. We assessed whether 7,8-dihydroneopterin could 1) protect against isometric force loss in wildtype skeletal muscle exposed to various pro-oxidants, and 2) protect wildtype and mdx muscle from eccentric contraction-induced force drop which has an oxidative component. Force drop was elicited in isolated Extensor Digitorum Longus (EDL) muscles by 10 eccentric contractions and recovery of force following the contractions was measured in the presence of exogenous 7,8-dihydroneopterin. 7,8-dihydroneopterin attenuated isometric force loss by wildtype EDL muscles when challenged by H 2 O 2 and HOCl, but exacerbated force loss when challenged by SIN-1 (NO · , O 2 · , ONOO - ). 7,8-dihydroneopterin attenuated eccentric contraction-induced force drop in mdx muscle. Isometric force by EDL muscles of mdx mice also recovered to a greater degree following eccentric contractions in the presence of 7,8-dihydroneopterin. The results corroborate macrophage activation in DMD patients, provide a potential protective role for 7,8-dihydroneopterin in the susceptibility of dystrophic muscle to eccentric contractions and indicate oxidative stress contributes to eccentric contraction-induced force drop in mdx skeletal muscle. This article is protected by copyright. All rights reserved. This article is protected by
D'Antoni, Michelle L; Paul, Robert H; Mitchell, Brooks I; Kohorn, Lindsay; Fischer, Laurent; Lefebvre, Eric; Seyedkazemi, Star; Nakamoto, Beau K; Walker, Maegen; Kallianpur, Kalpana J; Ogata-Arakaki, Debra; Ndhlovu, Lishomwa C; Shikuma, Cecilia
2018-05-16
To evaluate changes in neuropsychological (NP) performance and in plasma and cell surface markers of peripheral monocyte activation/migration following treatment with cenicriviroc (CVC), a dual C-C chemokine receptor type 2 (CCR2) and type 5 (CCR5) antagonist, in treatment-experienced, HIV-infected individuals. Single-arm, 24-week, open-label clinical trial. HIV-infected individuals on antiretroviral therapy (ART) >1 year with plasma HIV RNA <50 copies/ml and below-normal cognitive performance [defined as age, gender and education-adjusted NP performance (NPZ) <-0.5 in a single cognitive domain or in global performance] were enrolled. Changes over 24 weeks were assessed for global and domain-specific NPZ scores, plasma markers of monocyte/macrophage activation [neopterin, soluble (s)CD14 and sCD163] quantified by ELISA, and CCR2 and CCR5 expression on monocytes and T cells measured by flow cytometry. Seventeen of 20 enrolled participants completed the study. Improvements over 24 weeks were observed in global NPZ [median change (Δ)=0.24; p=0.008], and in cognitive domains of attention (Δ0.23; p=0.011) and working memory (Δ0.44; p=0.017). Plasma levels of sCD163, sCD14, and neopterin decreased significantly (p's<0.01). CCR2 and CCR5 monocyte expression remained unchanged; however, CCR5 levels on CD4 and CD8 T cells and CCR2 expression on CD4 T cells increased (p's<0.01). CVC given over 24 weeks was associated with improved NP test performance and decreased plasma markers of monocyte immune activation in virally-suppressed, HIV-infected participants. These data potentially link changes in monocyte activation to cognitive performance. Further study of CVC for HIV cognitive impairment in a randomized controlled study is warranted.
Tanhapour, M; Vaisi-Raygani, A; Bahrehmand, F; Khazaei, M; Kiani, A; Rahimi, Z; Nomani, H; Tavilani, H; Pourmotabbed, T
2016-10-31
The cytotoxic T lymphocyte antigen-4 (CTLA-4) also known as CD152 (cluster of differentiation 152) is a crucial negative regulator of the immune system. This protein receptor provides negative signals in order to suppress T-cell activation and immune attack against self-antigens, although its role is unclear. The ability of CTLA-4 to limit T cell-mediated immune response has made it a major target in treatment of tumors and autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we investigated whether CTLA-4 G-1661A and CTLA-4 T-1722C mutations are associated with SLE. So one hundred nine SLE patients and 101 gender and age-matched unrelated healthy controls were recruited for this case-control study. The promoter mutations were detected by PCR-RFLP, neopterin, malondialdehyde (MDA) and serum lipid concentration were determined by HPLC and enzyme assay, respectively. We found that both codominant (AA vs. GG) and recessive (AA vs. GA+GG) CTLA-4 G-1661A mutation significantly decreased the risk of SLE by 1.7 and 3.7 times, respectively. Interestingly, SLE patients with AA genotypes of CTLA-4 G-1661A have lower neopterin and MDA concentration compared with GA+GG genotypes. The overall distribution of CTLA-4 T-1722C genotypes and alleles in SLE patients were similar to those in control group. In conclusion, our findings showed, that there is an association between systemic inflammatory markers, oxidative stress and the CTLA-4 G-1661A GG+AG genotypes, MDA and neopterin which are the most conventional risk factors for coronary heart disease, therefore these mutations may be consider as a risk factor for susceptibility to heart disease in SLE patients.
Lindsay, A; Lewis, J G; Scarrott, C; Gill, N; Gieseg, S P; Draper, N
2015-06-01
Rugby union is a sport involving high force and frequency impacts making the likelihood of injury a significant risk. The aim of this study was to measure and report the individual and group acute and cumulative physiological stress response during 3 professional rugby games through non-invasive sampling. 24 professional rugby players volunteered for the study. Urine and saliva samples were collected pre and post 3 matches. Myoglobin, salivary immunoglobulin A, cortisol, neopterin and total neopterin (neopterin+7,8-dihydroneopterin) were analysed by high performance liquid chromatography or enzyme linked immunosorbent assay. Significant increases in cortisol, myoglobin, neopterin and total neopterin when urine volume was corrected with specific gravity were observed (p<0.05). Significant decreases in salivary immunoglobulin A concentration were observed for games 1 and 2 while secretion rate decreased after games 2 and 3. Significant decreases were seen with the percent of 7,8-dihydroneopterin being converted to neopterin following games 2 and 3. The intensity of 3 professional rugby games was sufficient to elicit significant changes in the physiological markers selected for our study. Furthermore, results suggest the selected markers not only provide a means for analysing the stress encountered during a single game of rugby but also highlight the unique pattern of response for each individual player. © Georg Thieme Verlag KG Stuttgart · New York.
Brunet, J L; Fatoohi, F; Liaudet, A Perret; Cozon, G J N
2002-02-01
Chronic fatigue syndrome or benign myalgic encephalomyelitis has been extensively described and investigated. Although numerous immunological abnormalities have been linked with the syndrome, none have been found to be specific. This article describes the detection of delayed-type hypersensitive responses to certain common environmental antigens in almost fifty per cent of patients with this syndrome. Such hypersensitivity can be detected by the intradermal administration of antigens derived from commensal organisms like the yeast Candida albicans, and then monitoring for a systemic reaction over the following six to forty eight hours. This approach can be consolidated by performing lymphocyte activation tests in parallel and measuring in vitro T-cell activation by Candida albicans antigens by three-colour flow cytometry based on CD3, CD4 and either CD69 or CD25. Another useful parameter is the kinetics of neopterin excretion in the urine over the course of the skin test. The results showed that the intensity of the DTH response correlated with the number of T-cells activated in vitro. Various factors have been implicated in the fatigue of many patients, notably lack of sleep. However, it remains difficult to establish causality in either one direction or the other. This work is in the spirit of a multifactorial approach to the group of conditions referred to as "chronic fatigue syndrome".
The physiological response to cold-water immersion following a mixed martial arts training session.
Lindsay, Angus; Carr, Sam; Cross, Sean; Petersen, Carl; Lewis, John G; Gieseg, Steven P
2017-05-01
Combative sport is one of the most physically intense forms of exercise, yet the effect of recovery interventions has been largely unexplored. We investigated the effect of cold-water immersion on structural, inflammatory, and physiological stress biomarkers following a mixed martial arts (MMA) contest preparation training session in comparison with passive recovery. Semiprofessional MMA competitors (n = 15) were randomly assigned to a cold-water immersion (15 min at 10 °C) or passive recovery protocol (ambient air) completed immediately following a contest preparation training session. Markers of muscle damage (urinary myoglobin), inflammation/oxidative stress (urinary neopterin + total neopterin (neopterin + 7,8-dihydroneopterin)), and hypothalamic-pituitary axis (HPA) activation (saliva cortisol) were determined before, immediately after, and 1, 2, and 24 h postsession. Ratings of perceived soreness and fatigue, counter movement jump, and gastrointestinal temperature were also measured. Concentrations of all biomarkers increased significantly (p < 0.05) postsession. Cold water immersion attenuated increases in urinary neopterin (p < 0.05, d = 0.58), total neopterin (p < 0.05, d = 0.89), and saliva cortisol after 2 h (p < 0.05, d = 0.68) and urinary neopterin again at 24 h (p < 0.01, d = 0.57) in comparison with passive recovery. Perceived soreness, fatigue, and gastrointestinal temperatures were also lower for the cold-water immersion group at several time points postsession whilst counter movement jump did not differ. Combative sport athletes who are subjected to impact-induced stress may benefit from immediate cold-water immersion as a simple recovery intervention that reduces delayed onset muscle soreness as well as macrophage and HPA activation whilst not impairing functional performance.
Peluso, Michael J.; Valcour, Victor; Phanuphak, Nittaya; Ananworanich, Jintanat; Fletcsher, James LK; Chalermchai, Thep; Krebs, Shelly J.; Robb, Merlin L.; Hellmuth, Joanna; Gisslén, Magnus; Zetterberg, Henrik; Spudich, Serena
2018-01-01
Objective To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. Design Cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. Methods AHI (n=33) and CHI (n=34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow up on cART in a subset of these individuals (6 months in AHI participants [n=24], 1 year in CHI participants [n=10]). Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations. Results Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/L; p=0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130 ng/L; p=0.003). In untreated CHI, YKL-40 correlated with neopterin (r=0.51, p=0.0025), chemokine (CXC-motif) ligand-10 (r=0.44, p=0.011), and neurofilament light chain (r=0.56, p=0.0008) in CSF. Conclusions This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI. PMID:27819802
Peluso, Michael J; Valcour, Victor; Phanuphak, Nittaya; Ananworanich, Jintanat; Fletcher, James L K; Chalermchai, Thep; Krebs, Shelly J; Robb, Merlin L; Hellmuth, Joanna; Gisslén, Magnus; Zetterberg, Henrik; Spudich, Serena
2017-01-14
To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. A cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. AHI (n = 33) and CHI (n = 34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow-up on cART in a subset of these individuals [6 months in AHI participants (n = 24), 1 year in CHI participants (n = 10)]. Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations. Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/l; P = 0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130 ng/l; P = 0.003). In untreated CHI, YKL-40 correlated with neopterin (r = 0.51, P = 0.0025), chemokine (CXC-motif) ligand-10 (r = 0.44, P = 0.011), and neurofilament light chain (r = 0.56, P = 0.0008) in CSF. This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI.
Edén, Arvid; Marcotte, Thomas D.; Heaton, Robert K.; Nilsson, Staffan; Zetterberg, Henrik; Fuchs, Dietmar; Franklin, Donald; Price, Richard W.; Grant, Igor; Letendre, Scott L.; Gisslén, Magnus
2016-01-01
Objective Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). Design and Methods We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. Results Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p<0.001) but not in the NCN group (r = -0.13; p = 0.3). Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06). Conclusions Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies. PMID:27295036
Edén, Arvid; Marcotte, Thomas D; Heaton, Robert K; Nilsson, Staffan; Zetterberg, Henrik; Fuchs, Dietmar; Franklin, Donald; Price, Richard W; Grant, Igor; Letendre, Scott L; Gisslén, Magnus
2016-01-01
Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p<0.001) but not in the NCN group (r = -0.13; p = 0.3). Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06). Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies.
Fecal Markers of Environmental Enteropathy and Subsequent Growth in Bangladeshi Children.
Arndt, Michael B; Richardson, Barbra A; Ahmed, Tahmeed; Mahfuz, Mustafa; Haque, Rashidul; John-Stewart, Grace C; Denno, Donna M; Petri, William A; Kosek, Margaret; Walson, Judd L
2016-09-07
Environmental enteropathy (EE), a subclinical intestinal disorder characterized by mucosal inflammation, reduced barrier integrity, and malabsorption, appears to be associated with increased risk of stunting in children in low- and middle-income countries. Fecal biomarkers indicative of EE (neopterin [NEO], myeloperoxidase [MPO], and alpha-1-antitrypsin [AAT]) have been negatively associated with 6-month linear growth. Associations between fecal markers (NEO, MPO, and AAT) and short-term linear growth were examined in a birth cohort of 246 children in Bangladesh. Marker concentrations were categorized in stool samples based on their distribution (< first quartile, interquartile range, > third quartile), and a 10-point composite EE score was calculated. Piecewise linear mixed-effects models were used to examine the association between markers measured quarterly (in months 3-21, 3-9, and 12-21) and 3-month change in length-for-age z-score (ΔLAZ). Children with high MPO levels at quarterly time points lost significantly more LAZ per 3-month period during the second year of life than those with low MPO (ΔLAZ = -0.100; 95% confidence interval = -0.167 to -0.032). AAT and NEO were not associated with growth; however, composite EE score was negatively associated with subsequent 3-month growth. In this cohort of children from an urban setting in Bangladesh, elevated MPO levels, but not NEO or AAT levels, were associated with decreases in short-term linear growth during the second year of life, supporting previous data suggesting the relevance of MPO as a marker of EE. © The American Society of Tropical Medicine and Hygiene.
Fuertig, René; Ceci, Angelo; Camus, Sandrine M; Bezard, Erwan; Luippold, Andreas H; Hengerer, Bastian
2016-09-01
The kynurenine (KYN) pathway is implicated in diseases such as cancer, psychiatric, neurodegenerative and autoimmune disorders. Measurement of KYN metabolite levels will help elucidating the involvement of the KYN pathway in the disease pathology and inform drug development. Samples of plasma, cerebrospinal fluid or brain tissue were spiked with deuterated internal standards, processed and analyzed by LC-MS/MS; analytes were chromatographically separated by gradient elution on a C18 reversed phase analytical column without derivatization. We established an LC-MS/MS method to measure 11 molecules, namely tryptophan, KYN, 3-OH-KYN, 3-OH-anthranilic acid, quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, serotonin, dopamine and neopterin within 5.5 min, with sufficient sensitivity to quantify these molecules in small sample volumes of plasma, cerebrospinal fluid and brain tissue.
Sato, Tomoo; Coler-Reilly, Ariella; Utsunomiya, Atae; Araya, Natsumi; Yagishita, Naoko; Ando, Hitoshi; Yamauchi, Junji; Inoue, Eisuke; Ueno, Takahiko; Hasegawa, Yasuhiro; Nishioka, Kusuki; Nakajima, Toshihiro; Jacobson, Steven; Izumo, Shuji; Yamano, Yoshihisa
2013-01-01
Background Human T-lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare chronic neuroinflammatory disease. Since the disease course of HAM/TSP varies among patients, there is a dire need for biomarkers capable of predicting the rate of disease progression. However, there have been no studies to date that have compared the prognostic values of multiple potential biomarkers for HAM/TSP. Methodology/Principal Findings Peripheral blood and cerebrospinal fluid (CSF) samples from HAM/TSP patients and HTLV-1-infected control subjects were obtained and tested retrospectively for several potential biomarkers, including chemokines and other cytokines, and nine optimal candidates were selected based on receiver operating characteristic (ROC) analysis. Next, we evaluated the relationship between these candidates and the rate of disease progression in HAM/TSP patients, beginning with a first cohort of 30 patients (Training Set) and proceeding to a second cohort of 23 patients (Test Set). We defined “deteriorating HAM/TSP” as distinctly worsening function (≥3 grades on Osame's Motor Disability Score (OMDS)) over four years and “stable HAM/TSP” as unchanged or only slightly worsened function (1 grade on OMDS) over four years, and we compared the levels of the candidate biomarkers in patients divided into these two groups. The CSF levels of chemokine (C-X-C motif) ligand 10 (CXCL10), CXCL9, and neopterin were well-correlated with disease progression, better even than HTLV-1 proviral load in PBMCs. Importantly, these results were validated using the Test Set. Conclusions/Significance As the CSF levels of CXCL10, CXCL9, and neopterin were the most strongly correlated with rate of disease progression, they represent the most viable candidates for HAM/TSP prognostic biomarkers. The identification of effective prognostic biomarkers could lead to earlier detection of high-risk patients, more patient-specific treatment
Antiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection
Sinclair, Elizabeth; Ronquillo, Rollie; Lollo, Nicole; Deeks, Steven G.; Hunt, Peter; Yiannoutsos, Constantin T.; Spudich, Serena; Price, Richard W.
2012-01-01
Objective To define the effect of antiretroviral therapy (ART) on activation of T cells in cerebrospinal fluid (CSF) and blood, and interactions of this activation with CSF HIV-1 RNA concentrations. Design Cross-sectional analysis of 14 HIV-negative subjects and 123 neuroasymptomatic HIV-1–infected subjects divided into 3 groups: not on ART (termed “offs”), on ART with plasma HIV-1 RNA >500 copies/mL (“failures”), and on ART with plasma HIV-1 RNA ≤500 copies/mL (“successes”). T-cell activation was measured by coexpression of CD38 and human leukocyte antigen DR (HLA-DR). Other measurements included CSF neopterin and white blood cell (WBC) counts. Results CD8 T-cell activation in CSF and blood was highly correlated across all subjects and was highest in the offs, lower in the failures, and lower still in the successes. While CD8 activation was reduced in failures compared to offs across the range of plasma HIV-1, it maintained a coincident relation to CSF HIV-1 in both viremic groups. In addition to correlation with CSF HIV-1 concentrations, CD8 activation in blood and CSF correlated with CSF WBCs and CSF neopterin. Multivariate analysis confirmed the association of blood CD8 T-cell activation, along with plasma HIV-1 RNA and CSF neopterin, with CSF HIV-1 RNA levels. Conclusions The similarity of CD8 T-cell activation in blood and CSF suggests these cells move from blood to CSF with only minor changes in CD38/HLA-DR expression. Differences in the relation of CD8 activation to HIV-1 concentrations in the blood and CSF in the 2 viremic groups suggest that changes in immune activation not only modulate CSF HIV-1 replication but also contribute to CSF treatment effects. The magnitude of systemic HIV-1 infection and intrathecal macrophage activation are also important determinants of CSF HIV-1 RNA levels. PMID:18362693
Markers of nonselective and specific NK cell activation.
Fogel, Leslie A; Sun, Michel M; Geurs, Theresa L; Carayannopoulos, Leonidas N; French, Anthony R
2013-06-15
NK cell activation is controlled by the integration of signals from cytokine receptors and germline-encoded activation and inhibitory receptors. NK cells undergo two distinct phases of activation during murine CMV (MCMV) infection: a nonselective phase mediated by proinflammatory cytokines and a specific phase driven by signaling through Ly49H, an NK cell activation receptor that recognizes infected cells. We sought to delineate cell surface markers that could distinguish NK cells that had been activated nonselectively from those that had been specifically activated through NK cell receptors. We demonstrated that stem cell Ag 1 (Sca-1) is highly upregulated during viral infections (to an even greater extent than CD69) and serves as a novel marker of early, nonselective NK cell activation. Indeed, a greater proportion of Sca-1(+) NK cells produced IFN-γ compared with Sca-1(-) NK cells during MCMV infection. In contrast to the universal upregulation of Sca-1 (as well as KLRG1) on NK cells early during MCMV infection, differential expression of Sca-1, as well as CD27 and KLRG1, was observed on Ly49H(+) and Ly49H(-) NK cells late during MCMV infection. Persistently elevated levels of KLRG1 in the context of downregulation of Sca-1 and CD27 were observed on NK cells that expressed Ly49H. Furthermore, the differential expression patterns of these cell surface markers were dependent on Ly49H recognition of its ligand and did not occur solely as a result of cellular proliferation. These findings demonstrate that a combination of Sca-1, CD27, and KLRG1 can distinguish NK cells nonselectively activated by cytokines from those specifically stimulated through activation receptors.
Ganz, Peter; Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Bao, Weihang; Preston, Gregory M; Welch, K Michael A
2017-12-01
Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes. We conducted a case-cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes. Time to stroke was evaluated by Cox proportional hazards models. There was no association between time to stroke and lipoprotein-associated phospholipase A 2 , monocyte chemoattractant protein-1, resistin, matrix metalloproteinase-9, N-terminal fragment of pro-B-type natriuretic peptide, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, or soluble CD40 ligand. In adjusted analyses, osteopontin (hazard ratio per SD change, 1.362; P <0.0001), neopterin (hazard ratio, 1.137; P =0.0107), myeloperoxidase (hazard ratio, 1.177; P =0.0022), and adiponectin (hazard ratio, 1.207; P =0.0013) were independently associated with outcome strokes. After adjustment for the Stroke Prognostic Instrument-II and treatment, osteopontin, neopterin, and myeloperoxidase remained independently associated with outcome strokes. The addition of these 3 biomarkers to Stroke Prognostic Instrument-II increased the area under the receiver operating characteristic curve by 0.023 ( P =0.015) and yielded a continuous net reclassification improvement (29.1%; P <0.0001) and an integrated discrimination improvement (42.3%; P <0.0001). Osteopontin, neopterin, and myeloperoxidase were independently associated with the risk of recurrent stroke and improved risk classification when added to a clinical risk algorithm. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT
Gostner, Johanna M; Schroecksnadel, Sebastian; Jenny, Marcel; Klein, Angela; Ueberall, Florian; Schennach, Harald; Fuchs, Dietmar
2015-01-01
Coffee consumption is considered to exert an influence on mood, the immune system, cardiovascular disease, and cancer development, but the mechanisms of action of coffee and its compounds are only partly known and understood. Immunomodulatory effects of filtered extracts of coffee and decaffeinated coffee as well as coffee compounds were investigated in human peripheral blood mononuclear cells (PBMCs) stimulated with mitogen phytohemagglutinin (PHA). The activation of PBMCs was monitored by the breakdown of tryptophan to kynurenine via enzyme indoleamine 2,3-dioxygenase (IDO) and the production of the immune activation marker neopterin by GTP-cyclohydrolase I (GCH1). Both of these biochemical pathways are induced during cellular immune activation in response to the Th1-type cytokine interferon-γ (IFN-γ). Filtered extracts of coffee and decaffeinated coffee both suppressed tryptophan breakdown and neopterin formation in mitogen-stimulated PBMCs efficiently and in a dose-dependent manner. Of 4 coffee compounds tested individually, only gallic acid and less strong also caffeic acid had a consistent suppressive influence but also affected cell viability, whereas pure caffeine and chlorogenic acid exerted no relevant effect in the PBMC assay. The parallel influence of extracts on tryptophan breakdown and neopterin production shows an anti-inflammatory and immunosuppressive property of coffee extracts and some of its compounds. When extrapolating the in vitro results to in vivo, IFN-γ-mediated breakdown of tryptophan could be counteracted by the consumption of coffee or decaffeinated coffee. This may increase tryptophan availability for the biosynthesis of the neurotransmitter 5-hydroxytryptamine (serotonin) and thereby improve mood and quality of life.
Lindsay, A; Healy, J; Mills, W; Lewis, J; Gill, N; Draper, N; Gieseg, S P
2016-03-01
Muscle damage caused through impacts in rugby union is known to increase oxidative stress and inflammation. Pterins have been used clinically as markers of oxidative stress, inflammation, and neurotransmitter synthesis. This study investigates the release of myoglobin from muscle tissue due to force-related impacts and how it is related to the subsequent oxidation of 7,8-dihydroneopterin to specific pterins. Effects of iron and myoglobin on 7,8-dihydroneopterin oxidation were examined in vitro via strong cation-exchange high-performance liquid chromatography (SCX-HPLC) analysis of neopterin, xanthopterin, and 7,8-dihydroxanthopterin. Urine samples were collected from 25 professional rugby players pre and post four games and analyzed for myoglobin by enzyme-linked immunosorbent assay, and 7,8-dihydroneopterin oxidation products by HPLC. Iron and myoglobin oxidized 7,8-dihydroneopterin to neopterin, xanthopterin, and 7,8-dihydroxanthopterin at concentrations at or above 10 μM and 50 μg/mL, respectively. All four games showed significant increases in myoglobin, neopterin, total neopterin, biopterin, and total biopterin, which correlated between each variable (P < 0.05). Myoglobin and iron facilitate 7,8-dihydroneopterin oxidation to neopterin and xanthopterin. In vivo delocalization of myoglobin due to muscle damage may contribute to oxidative stress and inflammation after rugby. Increased concentrations of biopterin and total biopterin may indicate production of nitric oxide and monoamine neurotransmitters in response to the physical stress. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Immune biomarkers in older adults: Role of physical activity.
Valdiglesias, Vanessa; Sánchez-Flores, María; Maseda, Ana; Lorenzo-López, Laura; Marcos-Pérez, Diego; López-Cortón, Ana; Strasser, Barbara; Fuchs, Dietmar; Laffon, Blanca; Millán-Calenti, José C; Pásaro, Eduardo
2017-01-01
Aging is associated with a decline in the normal functioning of the immune system. Several studies described the relationship between immunological alterations, including immunosenescence and inflammation, and aging or age-related outcomes, such as sarcopenia, depression, and neurodegenerative disorders. Physical activity is known to improve muscle function and to exert a number of benefits on older adult health, including reduced risk for heart and metabolic system chronic diseases. However, the positive influence of physical activity on the immune system has not been elucidated. In order to shed light on the role of physical activity in immune responses of older individuals, a number of immunological parameters comprising % lymphocyte subsets (CD3 + , CD4 + , CD8 + , CD19 + , and CD16 + 56 + ) and serum levels of neopterin and tryptophan metabolism products were evaluated in peripheral blood samples of older adults performing normal (N = 170) or reduced (N = 89) physical activity. In addition, the potential influence of other clinical and epidemiological factors was also considered. Results showed that subjects with reduced physical activity displayed significantly higher levels of CD4 + /CD8 + ratio, kynurenine/tryptophan ratio, and serum neopterin, along with lower %CD19 + cells and tryptophan concentrations. Further, some immunological biomarkers were associated with cognitive impairment and functional status. These data contribute to reinforce the postulation that physical activity supports healthy aging, particularly by helping to protect the immunological system from aging-related changes.
Physical Activity and Adiposity Markers at Older Ages: Accelerometer Vs Questionnaire Data
Sabia, Séverine; Cogranne, Pol; van Hees, Vincent T.; Bell, Joshua A.; Elbaz, Alexis; Kivimaki, Mika; Singh-Manoux, Archana
2015-01-01
Objective Physical activity is critically important for successful aging, but its effect on adiposity markers at older ages is unclear as much of the evidence comes from self-reported data on physical activity. We assessed the associations of questionnaire-assessed and accelerometer-assessed physical activity with adiposity markers in older adults. Design/Setting/Participants This was a cross-sectional study on 3940 participants (age range 60-83 years) of the Whitehall II study who completed a 20-item physical activity questionnaire and wore a wrist-mounted accelerometer for 9 days in 2012 and 2013. Measurements Total physical activity was estimated using metabolic equivalent hours/week for the questionnaire and mean acceleration for the accelerometer. Time spent in moderate-and-vigorous physical activity (MVPA) was also assessed by questionnaire and accelerometer. Adiposity assessment included body mass index, waist circumference, and fat mass index. Fat mass index was calculated as fat mass/height² (kg/m²), with fat mass estimated using bioimpedance. Results Greater total physical activity was associated with lower adiposity for all adiposity markers in a dose-response manner. In men, the strength of this association was 2.4 to 2.8 times stronger with the accelerometer than with questionnaire data. In women, it was 1.9 to 2.3 times stronger. For MVPA, questionnaire data in men suggested no further benefit for adiposity markers past 1 hour/week of activity. This was not the case for accelerometer-assessed MVPA where, for example, compared with men undertaking <1 hour/week of accelerometer-assessed MVPA, waist circumference was 3.06 (95% confidence interval 2.06–4.06) cm lower in those performing MVPA 1–2.5 hours/week, 4.69 (3.47–5.91) cm lower in those undertaking 2.5–4 hours/week, and 7.11 (5.93–8.29) cm lower in those performing ≥4 hours/week. Conclusions The association of physical activity with adiposity markers in older adults was
Shanmuganathan, Muthusamy V.; Krishnan, Subramanian; Fu, Xiaowei; Prasadarao, Nemani V.
2013-01-01
Macrophages serve as permissive niches for Escherichia coli (E. coli) K1 to attain high grade bacteremia in the pathogenesis of meningitis in neonates. Although pterin levels are a diagnostic marker for immune activation, the role of macrophages in pterin production and in the establishment of meningitis is unknown. Here, we demonstrate that macrophages infected with E. coli K1 produce both neopterin and biopterin through increased expression of GTP-cyclohydrolase 1 (GCH1). Of note, increased production of biopterin enhances the expression of Fc-gamma receptor I (CD64), which in turn, aided the entry of E. coli K1 in macrophages while increased neopterin suppresses reactive oxygen species (ROS), thereby aiding bacterial survival. Inhibition of GCH1 by 2, 4-Diamino-6-hydroxypyrimidine (DAHP) prevented the E. coli K1 induced expression of CD64 in macrophages in vitro and the development of bacteremia in a newborn mouse model of meningitis. These studies suggest that targeting GCH1 could be therapeutic strategy for preventing neonatal meningitis by E. coli K1. PMID:24161960
Schubert, Christian; Geser, Willi; Noisternig, Bianca; Fuchs, Dietmar; Welzenbach, Natalie; König, Paul; Schüßler, Gerhard; Ocaña-Peinado, Francisco M.; Lampe, Astrid
2012-01-01
Little is known about the dynamic characteristics of stress system activity during “life as it is lived”. Using as representative a study design as possible, this investigation sought to gain insights into this area. A healthy 25-year-old woman collected her entire urine over a period of 63 days in 12-h intervals (126 measurements) to determine cortisol and neopterin (immune activation marker) levels. In addition, she filled out questionnaires on emotional state and daily routine in 12-h intervals, and was interviewed weekly to identify emotionally negative and positive everyday incidents. Adjusted cross-correlational analyses revealed that stressful incidents were associated with cyclic response patterns in both urinary cortisol and urinary neopterin concentrations. Urinary cortisol levels first decreased 12–24 h after stressful incidents occurred (lag 1: −.178; p = 0.048) and then increased a total of 72–84 h later (lag 6: +.224; p = 0.013). Urinary neopterin levels first increased 0–12 h before the occurrence of stressful incidents (−lag 1: +.185; p = 0.040) and then decreased a total of 48–60 h following such stressors (lag 4: −.181; p = 0.044). Decreases in urinary neopterin levels were also found 24–36 and 48–60 h after increases in pensiveness (lag 2: −.215; p = 0.017) and depressiveness (lag 4: −.221; p = 0.014), respectively. Findings on emotionally positive incidents sharply contrasted with those dealing with negative experiences. Positive incidents were followed first by urinary cortisol concentration increases within 12 h (lag 0: +.290; p = 0.001) and then by decreases after a total of 60–72 h (lag 5: −.186; p = 0.039). Urinary neopterin levels first decreased 12–24 h before positive incidents occurred (−lag 2: −.233; p = 0.010) and then increased a total of 12–24 h following these incidents (lag 1: +.222; p = 0.014). As with previous investigations on patients with systemic
Kinetics and Mechanism of Chemical Marker Formation and Water-Activated Heat Generation
1994-05-01
activated chemical heaters. It has recently been discovered at the Army’s Natick, Massachusetts Research, Development & Engineering Center that certain...FUNDING NUMBERS 0 i Kinetics and Mechanism of Chemical Marker Formation and Water-Activated Heat Generation ~~ 3 6. AUTHOR(S) I-GZ05 Kenneth Kustin DI N...unlimited. rpIC Q.UA y uI sECTED 5 13. ABSTRACT (Maximum 200 words) n Research has been conducted on two projects: intrinsic chemical markers and water
Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms
Rőszer, Tamás
2015-01-01
The alternatively activated or M2 macrophages are immune cells with high phenotypic heterogeneity and are governing functions at the interface of immunity, tissue homeostasis, metabolism, and endocrine signaling. Today the M2 macrophages are identified based on the expression pattern of a set of M2 markers. These markers are transmembrane glycoproteins, scavenger receptors, enzymes, growth factors, hormones, cytokines, and cytokine receptors with diverse and often yet unexplored functions. This review discusses whether these M2 markers can be reliably used to identify M2 macrophages and define their functional subdivisions. Also, it provides an update on the novel signals of the tissue environment and the neuroendocrine system which shape the M2 activation. The possible evolutionary roots of the M2 macrophage functions are also discussed. PMID:26089604
Activation of Basophils Is a New and Sensitive Marker of Biocompatibility in Hemodialysis
Aljadi, Zenib; Mansouri, Ladan; Nopp, Anna; Paulsson, Josefin M; Winqvist, Ola; Russom, Aman; Ståhl, Mårten; Hylander, Britta; Jacobson, Stefan H; Lundahl, Joachim
2014-01-01
The hemodialysis procedure involves contact between peripheral blood and the surface of dialyzer membranes, which may lead to alterations in the pathways of innate and adaptive immunity. We aimed to study the effect of blood–membrane interaction on human peripheral basophils and neutrophils in hemodialysis with high- and low-permeability polysulfone dialyzers. The surface expression of CD203c (basophil selection marker) and CD63 (activation marker) after activation by the bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP) or anti-Fcε receptor I (FcεRI) antibody and the absolute number of basophils was investigated before and after hemodialysis with each of the dialyzers. Moreover, the expression on neutrophils of CD11b, the CD11b active epitope, and CD88 was analyzed in the same groups of individuals. The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared with that in healthy controls, but no differences were observed after activation by anti-FcεRI. During the hemodialysis procedure, the low-flux membrane induced up-regulation of CD63 expression on basophils, while passage through the high-flux membrane did not significantly alter the responsiveness. In addition, the absolute number of basophils was unchanged after hemodialysis with either of the dialyzers and compared with healthy controls. We found no significant differences in the expression of the neutrophil activation markers (CD11b, the active epitope of CD11b, and CD88) comparing the two different dialyzers before and after dialysis and healthy controls. Together, these findings suggest that alterations in basophil activity may be a useful marker of membrane bioincompatibility in hemodialysis. PMID:24712758
Rowiński, Rafał; Kozakiewicz, Mariusz; Kędziora-Kornatowska, Kornelia; Hübner-Woźniak, Elżbieta; Kędziora, Józef
2013-11-01
The aim of the present study was to examine the relationship between markers of oxidative stress and erythrocyte antioxidant enzyme activity and physical activity in older men and women. The present study included 481 participants (233 men and 248 women) in the age group 65-69 years (127 men and 125 women) and in the age group 90 years and over (106 men and 123 women). The classification of respondents by physical activity was based on answers to the question if, in the past 12 months, they engaged in any pastimes which require physical activity. The systemic oxidative stress status was assessed by measuring plasma iso-PGF2α and protein carbonyl concentration as well as erythrocyte antioxidant enzymes activity, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The concentration of plasma iso-PGF2α and protein carbonyls (CP) was lower in groups of younger men and women compared to the respective older groups. In all examined groups, physical activity resulted in decrease of these oxidative stress markers and simultaneously caused adaptive increase in the erythrocyte SOD activity. Additionally, in active younger men CAT, GPx, and GR activities were higher than in sedentary ones. In conclusion, oxidative stress increase is age-related, but physical activity can reduce oxidative stress markers and induce adaptive increase in the erythrocyte antioxidant enzyme activity, especially SOD, even in old and very old men and women. © 2013.
Neves Miranda, Valter Paulo; Gouveia Peluzio, Maria do Carmo; Rodrigues de Faria, Eliana; Castro Franceschini, Sylvia do Carmo; Eloiza Priore, Silvia
2015-05-01
The evaluation of inflammatory markers during adolescence can monitor different stages and manifestation of chronic diseases in adulthood. The control of the subclinical inflammation process through changes in lifestyle, especially in the practice of physical activity and dietary education can mitigate the effects of risk factors that trigger the process of atherosclerosis. To do a critical review regarding inflammatory markers as a risk factor of cardiovascular disease in relation to body composition, physical activity and assessment of nutritional status of adolescents. A literature review was performed in the following electronic databases: PUBMED, SCIELO and CONCHRANE COLLECTION. The following associated terms were used "inflammation AND cardiovascular diseases AND nutritional status OR body composition OR physical activity". There were topics created for the discussion of subjects: obesity and risk factors for cardiovascular disease during adolescence; expression of inflammatory markers in adolescence; development of cardiovascular disease with inflammatory markers, and finally, inflammatory markers, physical activity and nutritional evaluation. It was observed that the inflammatory markers may manifest in adolescence and be related to risk factors for cardiovascular diseases. Physical activity and nutritional evaluation featured as non-pharmacological measures to control the incidence of inflammatory markers and cardiovascular risk factor. Intervention studies may clarify how the adoption of a more proper lifestyle can influence the inflammatory process. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
Event-related wave activity in the EEG provides new marker of ADHD.
Alexander, David M; Hermens, Daniel F; Keage, Hannah A D; Clark, C Richard; Williams, Leanne M; Kohn, Michael R; Clarke, Simon D; Lamb, Chris; Gordon, Evian
2008-01-01
This study examines the utility of new measures of event-related spatio-temporal waves in the EEG as a marker of ADHD, previously shown to be closely related to the P3 ERP in an adult sample. Wave activity in the EEG was assessed during both an auditory Oddball and a visual continuous performance task (CPT) for an ADHD group ranging in age from 6 to 18 years and comprising mostly Combined and Inattentive subtypes, and for an age and gender matched control group. The ADHD subjects had less wave activity at low frequencies ( approximately 1 Hz) during both tasks. For auditory Oddball targets, this effect was shown to be related to smaller P3 ERP amplitudes. During CPT, the approximately 1 Hz wave activity in the ADHD subjects was inversely related to clinical and behavioral measures of hyperactivity and impulsivity. CPT wave activity at approximately 1 Hz was seen to "normalise" following treatment with stimulant medication. The results identify a deficit in low frequency wave activity as a new marker for ADHD associated with levels of hyperactivity and impulsivity. The marker is evident across a range of tasks and may be specific to ADHD. While lower approximately 1 Hz activity partly accounts for reduced P3 ERPs in ADHD, the effect also arises for tasks that do not elicit a P3. Deficits in behavioral inhibition are hypothesized to arise from underlying dysregulation of cortical inhibition.
Antinucleosome antibodies as a marker of active proliferative lupus nephritis.
Bigler, Cornelia; Lopez-Trascasa, Margarita; Potlukova, Eliska; Moll, Solange; Danner, Doris; Schaller, Monica; Trendelenburg, Marten
2008-04-01
Antinucleosome autoantibodies were previously described to be a marker of active lupus nephritis. However, the true prevalence of antinucleosome antibodies at the time of active proliferative lupus nephritis has not been well established. Therefore, the aim of this study is to define the prevalence and diagnostic value of autoantibodies against nucleosomes as a marker for active proliferative lupus nephritis. Prospective multicenter diagnostic test study. 35 adult patients with systemic lupus erythematosus (SLE) at the time of the renal biopsy showing active class III or IV lupus nephritis compared with 59 control patients with SLE. Levels of antinucleosome antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Kidney biopsy findings of class III or IV lupus nephritis at the time of sampling in a study population versus clinically inactive or no nephritis in a control population. Increased concentrations of antinucleosome antibodies were found in 31 of 35 patients (89%) with active proliferative lupus nephritis compared with 47 of 59 control patients (80%) with SLE. No significant difference between the 2 groups with regard to number of positive patients (P = 0.2) or antibody concentrations (P = 0.2) could be found. The area under the receiver operating characteristic curve as a marker of the accuracy of the test in discriminating between proliferative lupus nephritis and inactive/no nephritis in patients with SLE was 0.581 (95% confidence interval, 0.47 to 0.70; P = 0.2). Increased concentrations of anti-dsDNA antibodies were found in 33 of 35 patients (94.3%) with active proliferative lupus nephritis compared with 49 of 58 control patients (84.5%) with SLE (P = 0.2). In patients with proliferative lupus nephritis, significantly higher titers of anti-dsDNA antibodies were detected compared with control patients with SLE (P < 0.001). The area under the receiver operating characteristic curve in discriminating between proliferative lupus nephritis and
Shanmuganathan, Muthusamy V; Krishnan, Subramanian; Fu, Xiaowei; Prasadarao, Nemani V
2014-02-01
Macrophages serve as permissive niches for Escherichia coli (E. coli) K1 to attain high grade bacteremia in the pathogenesis of meningitis in neonates. Although pterin levels are a diagnostic marker for immune activation, the role of macrophages in pterin production and in the establishment of meningitis is unknown. Here, we demonstrate that macrophages infected with E. coli K1 produce both neopterin and biopterin through increased expression of GTP-cyclohydrolase 1 (GCH1). Of note, increased production of biopterin enhances the expression of Fc-gamma receptor I (CD64), which in turn, aided the entry of E. coli K1 in macrophages while increased neopterin suppresses reactive oxygen species (ROS), thereby aiding bacterial survival. Inhibition of GCH1 by 2, 4-Diamino-6-hydroxypyrimidine (DAHP) prevented the E. coli K1 induced expression of CD64 in macrophages in vitro and the development of bacteremia in a newborn mouse model of meningitis. These studies suggest that targeting GCH1 could be therapeutic strategy for preventing neonatal meningitis by E. coli K1. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Tola, Esra Nur; Yalcin, Serenat Eris; Dugan, Nadiye
2017-07-01
The aim of our study is to analyse the inflammatory markers and lipid accumulation product (LAP) index in nonobese adolescents and younger aged women with polycystic ovary syndrome (PCOS) compared with age and body mass index (BMI)-matched healthy controls and to determine whether the investigated parameters are potential markers for the etiopathogenesis of PCOS. We also aim to determine whether these inflammatory markers are predictive for developing some clinical implications, such as cardiovascular disease (CVD) and insulin resistance (IR), associated with PCOS. A total of 34 adolescents and younger aged females with PCOS, and 33 age and BMI-matched healthy controls were recruited for our study. All participants were nonobese (BMI<25). Neopterin (NEO), C-reactive protein (CRP) levels and complete blood parameters were assessed. LAP index and homeostasis model assessment of IR (HOMA-IR) were calculated; anthropometric, clinical and biochemical parameters were also recorded. Serum NEO, CRP levels and LAP index were significantly increased in nonobese adolescents and younger aged females with PCOS compared to healthy controls. We could not found any predictive effect of investigated inflammatory markers and LAP index on CVD risk among PCOS patients after adjustment for abdominal obesity. We also found a positive predictive effect of WBC and a negative predictive effect of lymphocytes on IR in PCOS patients after adjustment for abdominal obesity. We did not find any predictor effect of NEO on IR, but it was a positive predictive marker for an elevated HOMA-IR index. Elevated NEO, CRP levels and LAP index could have potential roles in the etiopathogenesis of PCOS in nonobese adolescents and younger aged females,NEO could be a predictive marker for elevated HOMA-IR index, and WBC and lymphocytes could be predictive for the development of IR among nonobese adolescents and younger aged females with PCOS. Copyright © 2017 Elsevier B.V. All rights reserved.
Tenascin-C is not a useful marker for disease activity in psoriasis.
Latijnhouwers, M A; Bergers, M; Kuijpers, A L; van der Vleuten, C J; Dijkman, H; van de Kerkhof, P C; Schalkwijk, J
1998-09-01
Tenascin-C is an extracellular matrix glycoprotein that is markedly upregulated in the dermis of psoriatic skin. In this study, we have addressed the question whether the presence of tenascin-C in the lesion or in serum is a marker for disease activity. Immunohistochemical staining of tenascin-C before and after treatment with different topical and systemic medication showed that tenascin-C remained abundant after clinical remission of lesions, indicating that downregulation of tenascin-C to normal values is a slow process. By using a sensitive enzyme-linked immunosorbent assay to measure levels of serum tenascin-C in psoriatic patients and unaffected individuals, we found that tenascin-C levels in most patients were within the normal range. Moreover, tenascin-C values did not correlate with disease activity. We conclude that tenascin-C is not useful as a marker for disease activity in psoriasis.
Spreading activation in emotional memory networks and the cumulative effects of somatic markers.
Foster, Paul S; Hubbard, Tyler; Campbell, Ransom W; Poole, Jonathan; Pridmore, Michael; Bell, Chris; Harrison, David W
2017-06-01
The theory of spreading activation proposes that the activation of a semantic memory node may spread along bidirectional associative links to other related nodes. Although this theory was originally proposed to explain semantic memory networks, a similar process may be said to exist with episodic or emotional memory networks. The Somatic Marker hypothesis proposes that remembering an emotional memory activates the somatic sensations associated with the memory. An integration of these two models suggests that as spreading activation in emotional memory networks increases, a greater number of associated somatic markers would become activated. This process would then result in greater changes in physiological functioning. We sought to investigate this possibility by having subjects recall words associated with sad and happy memories, in addition to a neutral condition. The average ages of the memories and the number of word memories recalled were then correlated with measures of heart rate and skin conductance. The results indicated significant positive correlations between the number of happy word memories and heart rate (r = .384, p = .022) and between the average ages of the sad memories and skin conductance (r = .556, p = .001). Unexpectedly, a significant negative relationship was found between the number of happy word memories and skin conductance (r = -.373, p = .025). The results provide partial support for our hypothesis, indicating that increasing spreading activation in emotional memory networks activates an increasing number of somatic markers and this is then reflected in greater physiological activity at the time of recalling the memories.
Lempicki, Marta; Rothenbuhler, Anya; Merzoug, Valérie; Franchi-Abella, Stéphanie; Chaussain, Catherine; Adamsbaum, Catherine; Linglart, Agnès
2017-01-01
X-linked hypophosphatemic rickets (XLH) is the most common form of inheritable rickets. Rickets treatment is monitored by assessing alkaline phosphatase (ALP) levels, clinical features, and radiographs. Our objectives were to describe the magnetic resonance imaging (MRI) features of XLH and to assess correlations with disease activity. Twenty-seven XLH patients (median age 9.2 years) were included in this prospective single-center observational study. XLH activity was assessed using height, leg bowing, dental abscess history, and serum ALP levels. We looked for correlations between MRI features and markers of disease activity. On MRI, the median maximum width of the physis was 5.6 mm (range 4.8-7.8; normal <1.5), being >1.5 mm in all of the patients. The appearance of the zone of provisional calcification was abnormal on 21 MRI images (78%), Harris lines were present on 24 (89%), and bone marrow signal abnormalities were present on 16 (59%). ALP levels correlated with the maximum physeal widening and with the transverse extent of the widening. MRI of the knee provides precise rickets patterns that are correlated with ALP, an established biochemical marker of the disease, avoiding X-ray exposure and providing surrogate quantitative markers of disease activity. © 2017 S. Karger AG, Basel.
Immunomodulatory properties of cacao extracts – potential consequences for medical applications
Becker, Kathrin; Geisler, Simon; Ueberall, Florian; Fuchs, Dietmar; Gostner, Johanna M.
2013-01-01
Anti-inflammatory properties of cacao, fruits of Theobroma cacao L. (Sterculiaceae), are well documented, and therapeutic applications are described for gastrointestinal, nervous, and cardiovascular abnormalities. Most, if not all of these disease conditions involve inflammation or immune activation processes. The pro-inflammatory cytokine interferon-γ (IFN-γ) and related biochemical pathways like tryptophan breakdown by indoleamine 2,3-dioxygenase (IDO) and neopterin formation are deeply involved in their pathogenesis. Neopterin concentrations and the kynurenine to tryptophan ratio (Kyn/Trp, an estimate of IDO activity) are elevated in a significant proportion of patients with virus infections, cancer, autoimmune syndrome, neurodegeneration, and coronary artery disease. Moreover, higher neopterin and Kyn/Trp concentrations are indicative for poor prognosis. When investigating the effect of aqueous or ethanolic extracts of cacao on IFN-γ, neopterin and Kyn/Trp concentrations in mitogen-stimulated human peripheral blood mononuclear cells, breakdown of tryptophan by IDO, and formation of neopterin and IFN-γ were dose-dependently suppressed. The effects observed in the cell-based assays are associated with the antioxidant activity of the cacao extracts as determined by the cell-free oxygen radical absorption capacity assay. The influence of cacao extracts on IDO activity could be of particular relevance for some of the beneficial health effects ascribed to cacao: tryptophan breakdown by IDO is strongly involved in immunoregulation, and the diminished availability of tryptophan limits the biosynthesis of neurotransmitter serotonin. The inhibition of tryptophan breakdown by cacao constituents could thus be relevant not only for immune system restoration in patients, but also contribute to mood elevation and thereby improve quality of life. However, the available data thus far are merely in vitro only and future studies need to investigate the influence of cacao on
Optimizing of the basophil activation test: Comparison of different basophil identification markers.
Eberlein, Bernadette; Hann, Rebekka; Eyerich, Stefanie; Pennino, Davide; Ring, Johannes; Schmidt-Weber, Carsten B; Buters, Jeroen
2015-01-01
Flowcytometric identification of basophils is a prerequisite for measuring activation of basophils with IgE-dependent or IgE-independent stimuli. Aim of this study was to compare different marker combinations in a simultaneous multicolor flowcytometric measurement. Ten patients with a grass pollen allergy and three controls were included in the study. Basophilic cells were gated by using anti-CCR3, anti-IgE, anti-CRTH2, anti-CD203c, and anti-CD3. Cells were activated by a monoclonal anti-FcεRI antibody, N-formyl-methionyl-leucyl-phenylalanine (fMLP), and the allergen extract Phleum pratense. The activation marker anti-CD63 was used. The highest relative number of basophils was found with anti-CCR3+ cells, anti-IgE+ and anti-IgE+ /anti-CD203c+ cells, the lowest with CRTH2+/CD203c+/CD3- cells. A very good and good concordance of CCR3+ cells was seen with CCR3+/CD3- cells and CRTH2+/CD203c+/CD3- cells in all experiments. The contamination of the CCR3+ population with CD3+ cells and the contamination of the IgE+-population with CCR3- cells and CD203- cells were the lowest compared to all other marker combinations. As the highest relative number of basophils was identified by anti-CCR3 followed by the anti-IgE and anti-IgE/antiCD203c positive population in most cases, these markers can generally be recommended for identification of basophils. If a basophil population with very high purity is needed, anti-IgE should be chosen. © 2014 International Clinical Cytometry Society.
Alsalman, Ola A.; Tucker, Denise; Vanneste, Sven
2016-01-01
Objective: This preliminary study examined if baseline measures of stress-related biomarkers as measured by salivary secretions of specific autonomic [measured by salivary α-amylase (sAA)], endocrine (measured by salivary cortisol), and immune (measured by salivary neopterin) responses are greater in male subjects with tinnitus in response to an induced-stress task. Method: Twenty male subjects with no significant hearing loss, 10 with tinnitus, and 10 without tinnitus were enrolled in this study.Salivary secretions were collected before and after the induced stress task at four different time intervals. Results: sAA levels were lower in the tinnitus group in comparison to subjects without tinnitus, suggesting impaired sympathetic activity in the subjects with tinnitus although these levels remained stable throughout the stress experiment.While no significant effects could be obtained for salivary cortisol or neopterin, salivary neopterin levels were trending toward significance over all measurements. Behavioral measures of stress were found to correlate negatively with measures of sAA and salivary neopterin. Conclusion: The results of this study suggest impaired stress-related sAA mechanisms in male subjects with tinnitus, as evidenced by the different stress reactions induced in the endocrine system (as measured by salivary cortisol) and the immune system (as measured by salivary neopterin). PMID:27489534
Takatani, Massanobu; Crispim, Myuki Esashika; Fraiji, Nelson; Stefani, Mariane Martins Araujo; Kiesslich, Dagmar
2017-01-01
ABSTRACT Clinical and laboratory parameters including blood and cerebrospinal fluid (CSF) neopterin were investigated in human-T-lymphotropic-virus-type-I associated-myelopathy/tropical-spastic-paraparesis-HAM/TSP and in HTLV-I carriers. HAM/TSP (n = 11, 2 males/9 females, median age = 48 years), recently diagnosed HTLV-I carriers (n = 21, 15 females/6 males, median age = 44 years), healthy individuals (n = 20, 10 males/10 females, median age = 34.6 years) from the Brazilian Amazon (Manaus, Amazonas State) were investigated. Neopterin was measured (IBL ELISA Neopterin, Germany) in serum samples of all the participants, in CSF of 9 HAM/TSP patients as well as in 6 carriers. In HAM/TSP patients, CSF cell counts, protein and glucose were measured, the Osame’s motor-disability-score/OMDS was determined, and brain/spinal cord magnetic-resonance-imaging (MRI) was performed. HAM/TSP patients had normal CSF glucose, leukocyte counts; and normal protein levels predominated. Brain-MRI showed white-matter lesions in 7 out of 11 HAM/TSP patients. OMDS varied from 2-8: 9 were able to walk, 2 were wheel-chair-users. The median serum neopterin concentration in HAM/TSP patients was 6.6 nmol/ L; min. 2.8- max. 12.5 nmol/ L); was lower in carriers (4.3 nmol/L; min. 2.7- max. 7.2 nmol/ L) as well as in healthy participants (4.7 nmol/ L; min. 2.7- max. 8.0 nmol/ L) (p < 0.05). CSF neopterin concentrations in HAM/TSP patients were higher than in serum samples, and higher compared to carriers (p < 0.05). Carriers had similar serum-CSF neopterin concentrations compared to healthy participants. Variable clinical and laboratory profiles were seen in HAM/TSP patients, however our results support the neopterin measurement as a potential biomarker of disease activity. PMID:28380116
Rousseau, Aurélie; Favier, Rémi; Van Dreden, Patrick
2009-09-01
One of the most frequently proposed mechanisms for pre-eclampsia refers to uteroplacental thrombosis. However, the contribution of classical thrombotic risk factors remains questionable. The aims of this study were to investigate the activities of thrombomodulin, tissue factor and procoagulant phospholipids to assess endothelial cell injury in pregnant women with pre-eclampsia and to compare them with other classical markers of vascular injury and thrombotic risk. Using three new functional assays we studied the plasma levels of these new markers in 35 healthy women, 30 healthy pregnant women, and 35 women with pre-eclampsia. We found that plasma levels of thrombomodulin activity, tissue factor activity and procoagulant phospholipids were significantly elevated in women with pre-eclampsia versus normal pregnant and non-pregnant women. It is thus suggested that elevated levels of these parameters in pre-eclampsia may reflect vascular endothelium damage, and may be a more valuable biomarker than antigen for the assessment of endothelial damage in pre-eclampsia. The high increased levels of procoagulant phospholipids and tissue factor activities in pre-eclampsia could suggest that the procoagulant potential may be implicated in this complication and makes these markers very promising for the understanding, follow-up and therapeutic handling of complicated pregnancy.
Bjørke-Monsen, Anne-Lise; Ulvik, Arve; Nilsen, Roy M.; Midttun, Øivind; Roth, Christine; Magnus, Per; Stoltenberg, Camilla; Vollset, Stein Emil; Reichborn-Kjennerud, Ted; Ueland, Per Magne
2016-01-01
Maternal nutrition and inflammation have been suggested as mediators in the development of various adverse pregnancy outcomes associated with maternal obesity. We have investigated the relation between pre-pregnancy BMI, B vitamin status, and inflammatory markers in a group of healthy pregnant women. Cobalamin, folate, pyridoxal 5′-phosphate, and riboflavin; and the metabolic markers homocysteine, methylmalonic acid, and 3-hydroxykynurenine/xanthurenic acid ratio (HK/XA); and markers of cellular inflammation, neopterin and kynurenine/tryptophan ratio (KTR) were determined in pregnancy week 18 and related to pre-pregnancy body mass index (BMI), in 2797 women from the Norwegian Mother and Child Cohort Study (MoBa). Pre-pregnancy BMI was inversely related to folate, cobalamin, pyridoxal 5′-phosphate (PLP), and riboflavin (p < 0.001), and associated with increased neopterin and KTR levels (p < 0.001). Inflammation seemed to be an independent predictor of low vitamin B6 status, as verified by low PLP and high HK/XA ratio. A high pre-pregnancy BMI is a risk factor for low B vitamin status and increased cellular inflammation. As an optimal micronutrient status is vital for normal fetal development, the observed lower B vitamin levels may contribute to adverse pregnancy outcomes associated with maternal obesity and B vitamin status should be assessed in women with high BMI before they get pregnant. PMID:27916904
2012-01-01
Introduction The current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA. Methods This study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerr's criteria, disease extent index-Takayasu, physician's global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay. Results Unacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity. Conclusions This study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity. PMID:23259466
Pagesy, Patrick; Tachet, Caroline; Mostefa-Kara, Ali; Larger, Etienne; Issad, Tarik
2018-06-11
O-linked-β-N-Acetylglucosaminylation (O-GlcNAcylation), a reversible post-translational modification involved in diabetic complications, is regulated by only two enzymes, O-linked N-acetylglucosamine transferase (OGT) and β-N-Acetylglucosaminidase (OGA). Increased OGA expression has been described previously in blood cells from patients with diabetes and was interpreted as an adaptative response to hyperglycemia-induced O-GlcNAcylation. OGA expression was thus proposed to have potential utility as a diagnostic marker. The present work was undertaken to determine whether determination of OGA enzymatic activity in blood cells could constitute a more rapidly accessible marker than OGA expression level measurements.Blood samples were obtained from patients with type 2 diabetes from the Department of Diabetology of the Cochin Hospital and healthy volunteers from the French blood Agency. OGA enzymatic activity and OGA mRNA expression levels were evaluated in leucocytes from patients with type 2 diabetes and from healthy donors.OGA activity was higher in leucocytes from patients with diabetes compared to control individuals. Surprisingly, OGA activity was not correlated hyperglycaemia markers (blood glucose, fructosamine, HbA 1c ) but was positively correlated with the inflammatory marker C-reactive protein. OGA mRNA levels were also increased in leucocytes from patients with diabetes and were correlated with mRNA coding for two pro-inflammatory proteins, TNFα and TxNIP.Therefore, OGA activity in leucocytes might be a more easily accessible biomarker than OGA expression levels. However, changes in OGA activity observed in patients with type 2 diabetes may reflect the inflammatory rather than the glycaemic status of these patients. © Georg Thieme Verlag KG Stuttgart · New York.
Neal, Jeremy L.; Lamp, Jane M.; Lowe, Nancy K.; Gillespie, Shannon L.; Sinnott, Loraine T.; Mccarthy, Donna O.
2014-01-01
Objectives To determine if labor-associated inflammatory markers differ between low-risk, nulliparous women in pre-active vs. active labor at hospital admission and over time. Study Design Prospective comparative study of low-risk, nulliparous women with spontaneous labor onset at term (N=118) sampled from two large Midwestern hospitals. Circulating concentrations of inflammatory markers were measured at admission and again 2 and 4 hours later: namely, neutrophil and monocyte counts; and serum inflammatory cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α, IL-10) and chemokines (IL-8). Biomarker concentrations and their patterns of change over time were compared between pre-active (n=63) and active (n=55) labor admission groups using Mann-Whitney U tests. Results Concentrations of IL-6 and IL-10 in the active labor admission group were significantly higher than concentrations in the pre-active labor admission group at all three time points. Neutrophil levels were significantly higher in the active group at 2 and 4 hours after admission. The rate of increase in neutrophils and IL-10 between admission and 2 hours later was faster in the active group (p<0.001 and p=0.003, respectively). Conclusions Circulating concentrations of several inflammatory biomarkers are higher and their rate of change over time since admission is faster among low-risk, nulliparous women admitted to hospitals in active labor, as compared to those admitted in pre-active labor. More research is needed to determine if progressive changes in inflammatory biomarkers might be a useful adjunct to improving the assessment of labor progression and determining the optimal timing of labor admission. PMID:25086275
Radon, K; Parera, D; Rose, D M; Jung, D; Vollrath, L
2001-05-01
There is growing public concern that radio frequency electromagnetic fields may have adverse biological effects. In the present study eight healthy male students were tested to see whether or not radio frequency electromagnetic fields as used in modern digital wireless telecommunication (GSM standard) have noticeable effects on salivary melatonin, cortisol, neopterin, and immunoglobulin A (sIgA) levels during and several hours after exposure. In a specifically designed, shielded experimental chamber, the circularly polarized electromagnetic field applied was transmitted by an antenna positioned 10 cm behind the head of upright sitting test persons. The carrier frequency of 900 MHz was pulsed with 217 Hz (average power flux density 1 W/m2). In double blind trials, each test person underwent a total of 20 randomly allotted 4 hour periods of exposure and sham exposure, equally distributed at day and night. The results obtained show that the salivary concentrations of melatonin, cortisol, neopterin and sIgA did not differ significantly between exposure and sham exposure. Copyright 2001 Wiley-Liss, Inc.
Corsetti, Roberto; Barassi, Alessandra; Perego, Silvia; Sansoni, Veronica; Rossi, Alessandra; Damele, Clara Anna Linda; Melzi D'Eril, Gianlodovico; Banfi, Giuseppe; Lombardi, Giovanni
2016-01-01
The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis.
Lavie, Carl J; Church, Timothy S; Milani, Richard V; Earnest, Conrad P
2011-01-01
Physical activity and exercise training (ET) enhance overall cardiorespiratory fitness (ie, fitness), thus producing many benefits in the primary and secondary prevention of cardiovascular diseases. Substantial evidence also indicates that acute and chronic inflammation is involved in the development and progression of atherosclerosis and major cardiovascular events. The most commonly utilized marker of inflammation is C-reactive protein (CRP). In this review, we discuss the importance of inflammation, especially CRP, as a cardiovascular risk marker by reviewing an abundant cross-sectional and clinical intervention literature providing evidence that physical activity, enhanced fitness, and ET are inversely associated with CRP and that being overweight or obese is directly related with inflammation/CRP. Although we discuss the controversy regarding whether or not ET reduces CRP independent of weight loss, clearly physical activity, improved fitness, and ET are associated with reductions in inflammation and overall cardiovascular risk in both primary and secondary prevention.
Delta-aminolevulinate dehydratase activity and oxidative stress markers in preeclampsia.
de Lucca, Leidiane; Rodrigues, Fabiane; Jantsch, Letícia B; Kober, Helena; Neme, Walter S; Gallarreta, Francisco M P; Gonçalves, Thissiane L
2016-12-01
Preeclampsia is an important pregnancy-specific multisystem disorder characterized by the onset of hypertension and proteinuria. It is of unknown etiology and involves serious risks for the pregnant women and fetus. One of the main factors involved in the pathophysiology of preeclampsia is oxidative stress, where excess free radicals produce harmful effects, including damage to macromolecules such as lipids, proteins and DNA. In addition, the sulfhydryl delta-aminolevulinate dehydratase enzyme (δ-ALA-D) that is part of the heme biosynthetic pathway in pro-oxidant conditions can be inhibited, which may result in the accumulation of 5-aminolevulinic acid (ALA), associated with the overproduction of free radicals, suggesting it to be an indirect marker of oxidative stress. As hypertensive pregnancy complications are a major cause of morbidity and mortality maternal and fetal where oxidative stress appears to be an important factor involved in preeclampsia, the aim of this study was to evaluate the activity of δ-ALA-D and classic oxidative stress markers in the blood of pregnant women with mild and severe preeclampsia. The analysis and quantification of the following oxidative stress markers were performed: thiobarbituric acid-reactive species (TBARS); presence of protein and non-protein thiol group; quantification of vitamin C; Catalase and δ-ALA--D activities in samples of blood of pregnant women with mild preeclampsia (n=25), with severe preeclampsia (n=30) and in a control group of healthy pregnant women (n=30). TBARS was significantly higher in women with preeclampsia, while the presence of thiol groups, levels of vitamin C, catalase and δ-ALA-D activity were significantly lower in groups of pregnant women with preeclampsia compared with healthy women. In addition, the results showed no significant difference between groups of pregnant women with mild and severe preeclampsia. The data suggest a state of increased oxidative stress in pregnant women with
Dahl, Viktor; Peterson, Julia; Fuchs, Dietmar; Gisslen, Magnus; Palmer, Sarah; Price, Richard W.
2015-01-01
Objective and design Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation. Methods CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens. Results CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P <0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7 nmol/l; P =0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4+ cell count or CNS penetration-efficacy score. Conclusion Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury. PMID:25022595
Dahl, Viktor; Peterson, Julia; Fuchs, Dietmar; Gisslen, Magnus; Palmer, Sarah; Price, Richard W
2014-09-24
Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation. CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens. CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P < 0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7 nmol/l; P = 0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4 cell count or CNS penetration-efficacy score. Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury.
Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.
Jessen Krut, Jan; Mellberg, Tomas; Price, Richard W; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus
2014-01-01
Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further
Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients
Price, Richard W.; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus
2014-01-01
Background Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. Methods With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. Results While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Conclusions Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and
TOMASSON, GUNNAR; LAVALLEY, MICHAEL; TANRIVERDI, KAHRAMAN; FINKIELMAN, JAVIER D.; DAVIS, JOHN C.; HOFFMAN, GARY S.; McCUNE, W. JOSEPH; St. CLAIR, E. WILLIAM; SPECKS, ULRICH; SPIERA, ROBERT; STONE, JOHN H.; FREEDMAN, JANE E.; MERKEL, PETER A.
2013-01-01
Objective There remains a need for biomarkers to guide therapy in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our objective was to determine whether measures of platelet activation or inflammation are associated with disease activity in Wegener’s granulomatosis (WG). Methods Study subjects were participants in a clinical trial. Soluble CD40 ligand (sCD40L), C-reactive protein, interleukin 6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), P-selectin, vascular endothelial growth factor, and proteinase 3 (PR3)-specific ANCA were measured by ELISA using plasma samples obtained at baseline (active disease), at remission, and prior to, during, and after first flares. Disease activity was assessed by the Birmingham Vasculitis Activity Score for WG (BVAS/WG). Association of biomarkers with disease activity was determined with conditional logistic and linear regression. Results Over a mean followup of 27 months, 180 subjects underwent 2044 visits; markers were measured in 563 samples. Longitudinally, all markers other than IL-6 were associated with disease activity. The strongest associations for active disease at baseline versus remission were observed for sCD40L (OR 4.72, 95% CI 2.47–9.03), P-selectin (OR 6.26, 95% CI 2.78–14.10), PR3-ANCA (OR 9.41, 4.03–21.99), and inversely for MCP-1 (OR 0.36, 95% CI 0.22–0.57). BVAS/WG increased by 0.80 (95% CI 0.44–1.16), 0.83 (95% CI 0.42–1.25), and 0.81 (95% CI 0.48–1.15) per unit-increase in PR3-ANCA, sCD40L, and P-selectin, respectively; and decreased by 1.54 (95% CI 0.96–2.12) per unit-increase in MCP-1. Conclusion Cytokines arising from within the circulation, including those of platelet activation, correlate with disease activity in WG. PMID:21411717
NASA Astrophysics Data System (ADS)
Mazurek, Przemysław
2013-09-01
Matchmoving (Match Moving) is the process used for the estimation of camera movements for further integration of acquired video image with computer graphics. The estimation of movements is possible using pattern recognition, 2D and 3D tracking algorithms. The main problem for the workflow is the partial occlusion of markers by the actor, because manual rotoscoping is necessary for fixing of the chroma-keyed footage. In the paper, the partial occlusion problem is solved using the invented, selectively active electronic markers. The sensor network with multiple infrared links detects occlusion state (no-occlusion, partial, full) and switch LED's based markers.
Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer.
Kawakami, Kyojiro; Fujita, Yasunori; Matsuda, Yoko; Arai, Tomio; Horie, Kengo; Kameyama, Koji; Kato, Taku; Masunaga, Koichi; Kasuya, Yutaka; Tanaka, Masashi; Mizutani, Kosuke; Deguchi, Takashi; Ito, Masafumi
2017-05-05
Exosomes or extracellular vesicles have the potential as a diagnostic marker for various diseases including cancer. In order to identify novel exosomal markers for prostate cancer (PC), we performed proteomic analysis of exosomes isolated from PC cell lines and examined the usefulness of the marker in patients. Exosomes isolated by differential centrifugation from the culture medium of androgen-dependent LNCaP prostate cancer cell line and its sublines of partially androgen-independent C4, androgen-independent C4-2 and bone metastatic C4-2B were subjected to iTRAQ-based proteomic analysis. Exosomes were also isolated by immunocapture and separated by size exclusion chromatography and density gradient centrifugation. Protein expression was determined by Western blot analysis. GGT activity was measured using a fluorescent probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG). Immunohistochemical analysis of tissues was performed using anti-GGT1 antibody. Among proteins upregulated in C4-2 and C4-2B cells than in LNCaP cells, we focused on gamma-glutamyltransferase 1 (GGT1), a cell-surface enzyme that regulates the catabolism of extracellular glutathione. The levels of both GGT1 large and small subunits were elevated in exosomes isolated from C4-2 and C4-2B cells by differential centrifugation and by immunocapture with anti-CD9 or -prostate-specific membrane antigen (PSMA) antibody. In cell lysates and exosomes, GGT1 expression correlated with GGT activity. Size exclusion chromatography of human serum demonstrated the presence of GGT activity and GGT1 subunits in fractions positive for CD9. Density gradient centrifugation revealed the co-presence of GGT1 subunits with CD9 in exosomes isolated by differential centrifugation from human serum. Since GGT activity correlated with GGT1 expression in serum exosomes isolated by differential centrifugation, we measured serum exosomal GGT activity in patients. Unexpectedly, we found that serum exosomal GGT activity was
Serum prolactin in coeliac disease: a marker for disease activity
Reifen, R.; Buskila, D.; Maislos, M.; Press, J.; Lerner, A.
1997-01-01
Accepted 21 April 1997 Prolactin, a polypeptide hormone of anterior pituitary origin, has pronounced physiological effects on growth, reproduction, and osmoregulation. Increasing evidence indicates that prolactin also has an immunomodulatory influence on the immune system. The status of prolactin in patients with coeliac disease was investigated by obtaining serum samples from 48 patients with active and non-active coeliac disease. These were compared with samples from 20 children with familial Mediterranean fever and 65 normal controls. Serum prolactin in patients with active coeliac disease was significantly higher than in the other groups studied and reference values. Serum prolactin correlated well with the degree of mucosal atrophy and with the serum concentration of antiendomysial antibodies. Prolactin may play a part in immune modulation in the intestinal damage of coeliac disease and serve as a potential marker for disease activity. PMID:9301358
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-08
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Tuisku, Katinka; Holi, Matti Mikael; Wahlbeck, Kristian; Ahlgren, Aulikki Johanna; Lauerma, Hannu
2003-04-01
An objective marker of restless legs syndrome (RLS) is needed for developing diagnostic tools and monitoring symptoms. Actometric ambulatory monitoring of 15 RLS patients and 15 healthy controls was undertaken in order to differentiate between RLS-related motor symptoms and normal motor activity. Nocturnal lower-limb activity per minute differentiated and discriminated between groups with no overlap, whereas the periodic limb movement index and the controlled rest activity during sitting showed less discriminative power. The naturalistic recording of nocturnal activity by actometry may prove useful for assessing the severity of RLS and for finding an objective marker to support the diagnosis of RLS. Copyright 2002 Movement Disorder Society
Chow, E; Hird, A; Zhang, Liying; Sinclair, E; Danjoux, C; Barnes, E; Tsao, M; Barbera, L; Wong, Shun; Vieth, R
2009-05-01
To examine the effect of radiotherapy for bone metastases on urinary markers of osteoclast activity. Patients with radiological evidence of bone metastases planned for palliative radiotherapy were eligible for the study. A urine specimen was collected before and 1 month after radiotherapy to assess levels of calcium, creatinine, magnesium, phosphate, N-telopeptide and pyridinoline. The Brief Pain Inventory was completed in person at baseline and by telephone follow-up at 1 month after radiotherapy. Patients were classified as responders (complete or partial pain response) or non-responders (stable or progressive pain) to radiotherapy based on the International Bone Metastases Consensus Criteria for end point measurements. Absolute values of urine markers were compared between responders and non-responders, or between responders and patients with progression. Our study population consisted of 74 men and 51 women. A single 8 Gy or 20 Gy in five daily fractions were commonly employed. At the 1 month follow-up, all Brief Pain Inventory functional interference scores showed a highly significant decrease from baseline (P<0.01). From our study population, 58 (64%) were classified as responders and 57 (46%) as non-responders to radiotherapy. We compared the urinary markers between the responders and the non-responders. There were no statistically significant differences between the two groups either in terms of baseline markers or in terms of month 1 follow-up markers. There was no significant change from baseline to the 1 month follow-up in responders or in non-responders to radiotherapy. Baseline levels of urinary markers could not predict which patient would benefit from palliative radiotherapy.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-27
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-21
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Maes, Michael; Ringel, Karl; Kubera, Marta; Berk, Michael; Rybakowski, Janusz
2012-02-01
Depression is characterized by inflammation and cell-mediated immune (CMI) activation and autoimmune reactions directed against a multitude of self-epitopes. There is evidence that the inflammatory response in depression causes dysfunctions in the metabolism of 5-HT, e.g. lowering the 5-HT precursor tryptophan, and upregulating 5-HT receptor mRNA. This study has been undertaken to examine autoimmune activity directed against 5-HT in relation to CMI activation and inflammation. 5-HT antibodies were examined in major depressed patients (n=109) versus normal controls (n=35) in relation to serum neopterin and lysozyme, and plasma pro-inflammatory cytokines (PIC), i.e. interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of fatigue and somatic symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. The incidence of anti-5-HT antibody activity was significantly higher in depressed patients (54.1%), and in particular in those with melancholia (82.9%), than in controls (5.7%). Patients with positive 5-HT antibodies showed increased serum neopterin and lysozyme, and plasma TNFα and IL-1; higher scores on the HDRS and FF scales, and more somatic symptoms, including malaise and neurocognitive dysfunctions. There was a significant association between autoimmune activity to 5-HT and the number of previous depressive episodes. The autoimmune reactions directed against 5-HT might play a role in the pathophysiology of depression and the onset of severe depression. The strong association between autoimmune activity against 5-HT and inflammation/CMI activation is explained by multiple, reciprocal pathways between these factors. Exposure to previous depressive episodes increases the incidence of autoimmune activity directed against 5-HT, which in turn may increase the likelihood to develop new depressive episodes. These findings suggest that sensitization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sigal, G. B.; Segal, M. R.; Mathew, A.
More efficacious treatment regimens are needed for tuberculosis, however, drug development is impeded by a lack of reliable biomarkers of disease severity and of treatment effect. We conducted a directed screen of host biomarkers in participants enrolled in a tuberculosis clinical trial to address this need. Serum samples from 319 protocol-correct, culture-confirmed pulmonary tuberculosis patients treated under direct observation as part of an international, phase 2 trial were screened for 70 markers of infection, inflammation, and metabolism. Biomarker assays were specifically developed for this study and quantified using a novel, multiplexed electrochemiluminescence assay. We evaluated the association of biomarkers withmore » baseline characteristics, as well as with detailed microbiologic data, using Bonferroni-adjusted, linear regression models. Across numerous analyses, seven proteins, SAA1, PCT, IL-1, IL-6, CRP, PTX-3 and MMP-8, showed recurring strong associations with markers of baseline disease severity, smear grade and cavitation; were strongly modulated by tuberculosis treatment; and had responses that were greater for patients who culture-converted at 8 weeks. With treatment, all proteins decreased, except for osteocalcin, MCP-1 and MCP-4, which significantly increased. Several previously reported putative tuberculosis-associated biomarkers (HOMX1, neopterin, and cathelicidin) were not significantly associated with treatment response. In conclusion, across a geographically diverse and large population of tuberculosis patients enrolled in a clinical trial, several previously reported putative biomarkers were not significantly associated with treatment response, however, seven proteins had recurring strong associations with baseline radiographic and microbiologic measures of disease severity, as well as with early treatment response, deserving additional study. Keywords: host immune response; tuberculosis; biomarkers; clinical trials« less
Association of markers of bacterial translocation with immune activation in decompensated cirrhosis.
Mortensen, Christian; Jensen, Jørgen Skov; Hobolth, Lise; Dam-Larsen, Sanne; Madsen, Bjørn S; Andersen, Ove; Møller, Søren; Bendtsen, Flemming
2014-12-01
Bacterial translocation (BT) may cause infections, in particular, spontaneous bacterial peritonitis (SBP). In the absence of overt infection, BT may further stimulate the immune system and contribute to haemodynamic alterations and complications. Bacterial DNA (bDNA) is claimed to be a promising surrogate marker for BT, although its clinical relevance has been questioned. In 38 cirrhotic patients with and without SBP, bDNA in blood and ascites were assessed by 16S rDNA quantitative PCR. Levels of lipopolysaccharide-binding protein in plasma and highly sensitive C-reactive protein, tumour necrosis factor-α, soluble urokinase plasminogen activating receptor, interleukin-6, interleukin 8, interferon-γ inducible protein-10 and vascular endothelial growth factor in plasma and ascites were measured by multiplex cytokine and ELISA assays. In patients without signs of SBP or positive cultures, we found a high frequency of bDNA but low concordance of bDNA between blood and ascites. Markers of inflammation were not significantly different between blood bDNA-positive (22%), ascites bDNA-positive (52%), and bDNA-negative patients. The 16S rDNA PCR failed to show bDNA in two out of six samples with SBP. Sequencing of positive samples did not determine the source of bDNA. bDNA as assessed by this PCR method was largely unrelated to markers of inflammation and does not seem to be of clinical value in the diagnosis of SBP. According to our results, bDNA is not a reliable marker of BT.
Serum Adipocytokine Levels as Surrogate Markers for Disease Activity of Crohn's Disease.
Kim, Su Hwan; Jang, Seung Hyeon; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Kim, You Sun; Han, Dong Soo; Kim, Joo Sung
2017-05-01
Determining inflammatory activity is crucial for assessing disease activity and for tailoring therapy in patients with Crohn׳s disease (CD). This study aimed to evaluate adipocytokine levels in patients with CD and to determine whether they can serve as surrogate markers for disease activity. Serum samples and information regarding the clinical features of patients in the CD Network Project registry were collected from March 2009 to February 2012. Patients with CD and disease duration of at least 2 years were enrolled in this study. Fasting serum leptin, adiponectin, obestatin and ghrelin levels were measured, and their correlation with clinical features of the patients was analyzed. Serum adipocytokine levels were evaluated according to disease activity as determined by CD activity index score. A total of 153 patients with CD were included. Serum ghrelin levels negatively correlated with patient age (P = 0.041) and age at diagnosis (P = 0.017), and positively correlated with C-reactive protein (CRP) levels (P = 0.017). Multiple regression analysis showed that serum ghrelin levels were related only to CRP levels (P = 0.032). Like ghrelin, serum leptin levels were also related to CRP levels (P < 0.001). Obestatin and adiponectin levels were not related to CRP levels. Serum adipocytokine levels did not significantly differ across different disease locations or behaviors. Serum ghrelin levels were significantly lower in patients with CD with a history of surgery than in those without (P = 0.007). Serum ghrelin and leptin levels may be useful as surrogate markers for disease activity in patients with CD. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
Niederkorn, Anna; Frühauf, Julia; Schwantzer, Gerold; Wutte, Nora; Painsi, Clemens; Werner, Stefan; Stradner, Martin; Berghold, Andrea; Hermann, Josef; Aberer, Elisabeth
2018-05-04
Serum levels of the IFN-regulated cytokine CXCL13 have been found to correlate with SLEDAI and renal involvement in systemic lupus erythematosus. This study investigates whether CXCL13 can also be a marker of disease activity in patients with subacute cutaneous or chronic cutaneous lupus erythematosus (SCLE, CCLE). We analysed CXCL13 levels in 60 patients' sera (18 SLE, 19 SCLE, 23 CCLE) at five time points within 1 year and correlated these levels with disease activity scores and laboratory markers. Clinical scores with no/mild, moderate or high/severe disease activity were categorized by SLEDAI in SLE, by CLASI in SCLE/CCLE. CXCL13 levels were significantly higher in SLE (median 122.5, IQR 88.0-239.0 pg/ml) than in CCLE patients (median 69.0, IQR 60.0-102.0 pg/ml) (p = 0.006). CXCL13 levels were elevated in 59% (41/70) of SLE patient visits with mild or no disease activity, but in 90% (9/10) with high disease activity. CXCL13 levels correlated with ECLAM, dsDNA-antibodies, and inversely with complement factors C3 and C4 in SLE, and with IgA and ESR in SCLE. In CCLE CXCL13 did not correlate with CLASI or laboratory markers. One SCLE and two CCLE patients with CXCL13 levels > 500 pg/ml had conversion to SLE or an underlying autoimmune disease. CXCL13 seems to be a useful marker of disease activity in SLE, but not in SCLE and CCLE. Conversion from normal to elevated CXCL13 may indicate a flare of SLE. Whether high CXCL13 levels in cutaneous LE indicate the development of SLE should be further investigated.
Spudich, Serena; Gisslen, Magnus; Hagberg, Lars; Lee, Evelyn; Liegler, Teri; Brew, Bruce; Fuchs, Dietmar; Tambussi, Giuseppe; Cinque, Paola; Hecht, Frederick M; Price, Richard W
2011-09-01
Central nervous system (CNS) human immunodeficiency virus (HIV) infection and immune activation lead to brain injury and neurological impairment. Although HIV enters the nervous system soon after transmission, the magnitude of infection and immunoactivation within the CNS during primary HIV infection (PHI) has not been characterized. This cross-sectional study analyzed cerebrospinal fluid (CSF) and blood from 96 participants with PHI and compared them with samples from neuroasymptomatic participants with chronic infection and ≥ 200 or < 200 blood CD4 T cells/μL, and with samples from HIV-seronegative participants with respect to CSF and plasma HIV RNA, CSF to serum albumin ratio, and CSF white blood cell counts (WBC), neopterin levels, and concentrations of chemokines CXCL10 and CCL2. The PHI participants (median 77 days post transmission) had CSF HIV RNA, WBC, neopterin, and CXCL10 concentrations similar to the chronic infection participants but uniquely high albumin ratios. 18 participants had ≤ 100 copies/mL CSF HIV RNA, which was associated with low CSF to plasma HIV ratios and levels of CSF inflammation lower than in other PHI participants but higher than in HIV-seronegative controls. Prominent CNS infection and immune activation is evident during the first months after HIV transmission, though a proportion of PHI patients demonstrate relatively reduced CSF HIV RNA and inflammation during this early period.
Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV.
Anesten, Birgitta; Yilmaz, Aylin; Hagberg, Lars; Zetterberg, Henrik; Nilsson, Staffan; Brew, Bruce J; Fuchs, Dietmar; Price, Richard W; Gisslén, Magnus
2016-12-01
Although blood-brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined. BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART). The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis. BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals.
Occludin as a functional marker of vascular endothelial cells on tube-forming activity.
Kanayasu-Toyoda, Toshie; Ishii-Watabe, Akiko; Kikuchi, Yutaka; Kitagawa, Hiroko; Suzuki, Hiroko; Tamura, Hiroomi; Tada, Minoru; Suzuki, Takuo; Mizuguchi, Hiroyuki; Yamaguchi, Teruhide
2018-02-01
Cell therapy using endothelial progenitor cells (EPCs) is a promising strategy for the treatment of ischemic diseases. Two types of EPCs have been identified: early EPCs and late EPCs. Late EPCs are able to form tube structure by themselves, and have a high proliferative ability. The functional marker(s) of late EPCs, which relate to their therapeutic potential, have not been fully elucidated. Here we compared the gene expression profiles of several human cord blood derived late EPC lines which exhibit different tube formation activity, and we observed that the expression of occludin (OCLN) in these lines correlated with the tube formation ability, suggesting that OCLN is a candidate functional marker of late EPCs. When OCLN was knocked down by transfecting siRNA, the tube formation on Matrigel, the S phase + G 2 /M phase in the cell cycle, and the spheroid-based sprouting of late EPCs were markedly reduced, suggesting the critical role of OCLN in tube formation, sprouting, and proliferation. These results indicated that OCLN plays a novel role in neovascularization and angiogenesis. © 2017 Wiley Periodicals, Inc.
Morgan, Angela J; Guillen, Cristina; Symon, Fiona A; Birring, Surinder S; Campbell, James J; Wardlaw, Andrew J
2008-01-01
Expressions of activation markers have been described on the surface of T cells in the blood and the lung in both health and disease. We have studied the distribution of activation markers on human lung T cells and have found that only certain populations exist. Importantly, the presence or absence of some markers appears to predict those of others, in particular cells which express CD103 also express CD49a and CD69, whereas cells which do not express CD69 also do not express CD49a or CD103. In view of the paucity of activation marker expression in the peripheral blood, we have hypothesised that these CD69+, CD49a+, and CD103+ (triple positive) cells are retained in the lung, possess effector function (IFNgamma secretion) and express particular chemokine receptors which allow them to be maintained in this environment. We have found that the ability of the triple negative cells to secrete IFNgamma is significantly less than the triple positive cells, suggesting that the expression of activation markers can highlight a highly specialised effector cell. We have studied the expression of 14 chemokine receptors and have found that the most striking difference between the triple negative cells and the triple positive cells is the expression of CXCR6 with 12.8+/-9.8% of triple negative cells expressing CXCR6 compared to 89.5+/-5.5% of triple positive cells. We propose therefore that CXCR6 may play an important role in the retention of T cells within the lung.
Remmel, Liina; Tillmann, Vallo; Mengel, Eva; Kool, Pille; Purge, Priit; Lätt, Evelin; Jürimäe, Jaak
2018-05-01
To investigate the differences in the pattern of changes in serum inflammatory cytokines measured annually over a 24-month period, between less active and more active overweight boys. In total, 25 pubertal overweight boys were divided by their moderate to vigorous physical activity (MVPA) levels into 2 groups: less active group (LAG; n = 10; MVPA < 60 min/d) and more active group (MAG; n = 15; MVPA > 60 min/d). Physical activity was measured by 7-day accelerometry. Serum concentration of 13 inflammatory cytokines [interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, vascular endothelial growth factor, interferon-γ, tumor necrosis factor-α, monocyte chemotactic protein-1, epidermal growth factor, and C-reactive protein] was measured at baseline (T0), after 12 months (T1), and after 24 months (T2) from fasting blood samples. Serum IL-6 level was significantly higher [LAG: 1.27 (0.86, 1.98) pg/mL; MAG: 0.80 (0.52, 0.84) pg/mL] at T0 and IL-8 level [LAG: 10.26 (8.80, 11.64) pg/mL; MAG: 7.42 (6.10, 9.54) pg/mL] at T2 in LAG compared with MAG. The changes over the study period varied between different inflammatory markers. None of the slopes of any measured markers were statistically different between the LAG and MAG, although the slopes of interferon-γ and IL-10 tended to be different between the groups. The pattern of changes over the study period varied between different inflammatory markers, but these changes were not different between the MVPA groups. More longitudinal studies are needed to investigate whether IL-6, IL-8, IL-10, and interferon-γ would be the choice of inflammatory markers to study the associations between obesity and physical activity in future.
Characterizing proton-activated materials to develop PET-mediated proton range verification markers
NASA Astrophysics Data System (ADS)
Cho, Jongmin; Ibbott, Geoffrey S.; Kerr, Matthew D.; Amos, Richard A.; Stingo, Francesco C.; Marom, Edith M.; Truong, Mylene T.; Palacio, Diana M.; Betancourt, Sonia L.; Erasmus, Jeremy J.; DeGroot, Patricia M.; Carter, Brett W.; Gladish, Gregory W.; Sabloff, Bradley S.; Benveniste, Marcelo F.; Godoy, Myrna C.; Patil, Shekhar; Sorensen, James; Mawlawi, Osama R.
2016-06-01
Conventional proton beam range verification using positron emission tomography (PET) relies on tissue activation alone and therefore requires particle therapy PET whose installation can represent a large financial burden for many centers. Previously, we showed the feasibility of developing patient implantable markers using high proton cross-section materials (18O, Cu, and 68Zn) for in vivo proton range verification using conventional PET scanners. In this technical note, we characterize those materials to test their usability in more clinically relevant conditions. Two phantoms made of low-density balsa wood (~0.1 g cm-3) and beef (~1.0 g cm-3) were embedded with Cu or 68Zn foils of several volumes (10-50 mm3). The metal foils were positioned at several depths in the dose fall-off region, which had been determined from our previous study. The phantoms were then irradiated with different proton doses (1-5 Gy). After irradiation, the phantoms with the embedded foils were moved to a diagnostic PET scanner and imaged. The acquired data were reconstructed with 20-40 min of scan time using various delay times (30-150 min) to determine the maximum contrast-to-noise ratio. The resultant PET/computed tomography (CT) fusion images of the activated foils were then examined and the foils’ PET signal strength/visibility was scored on a 5 point scale by 13 radiologists experienced in nuclear medicine. For both phantoms, the visibility of activated foils increased in proportion to the foil volume, dose, and PET scan time. A linear model was constructed with visibility scores as the response variable and all other factors (marker material, phantom material, dose, and PET scan time) as covariates. Using the linear model, volumes of foils that provided adequate visibility (score 3) were determined for each dose and PET scan time. The foil volumes that were determined will be used as a guideline in developing practical implantable markers.
IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease Activity
Colafrancesco, Serena; Priori, Roberta; Alessandri, Cristiano; Perricone, Carlo; Pendolino, Monica; Picarelli, Giovanna; Valesini, Guido
2012-01-01
Introduction. Immunological factors seem to play a pivotal role in Adult Onset Still's Disease (AOSD). Among all, IL-18 cytokine is overexpressed and drives the inflammatory process. Objective. We aimed to investigate the levels of IL-18 in sera of Italian patients with AOSD and to assess its possible role as a marker of disease activity. Methods. IL-18 serum levels were determined by ELISA in 26 Italian patients with AOSD. Disease activity was assessed using Pouchot's criteria. As controls, 21 patients with Rheumatoid Arthritis (RA), 21 patients with Sjogren's Syndrome (SS), 20 patients with Systemic Lupus Erythematosus (SLE), and 21 healthy subjects (normal human sera, NHS) were evaluated. Results. IL-18 serum levels were significantly higher in patients with active AOSD than in non-active (P = 0.001) and control groups (RA P = 0.0070, SS P = 0.0029, SLE P = 0.0032, NHS P = 0.0004). A significant correlation between IL-18 serum levels and disease activity (P < 0.0001), and laboratory parameters as ferritin (P = 0.0127) and C-reactive protein (P = 0.0032) was demonstrated. Conclusions. Higher levels of IL-18 are detected in active AODS patients and correlate with disease activity and inflammatory laboratory features. ROC-AUC analysis of the serum concentration of IL-18 suggests that it can be considered a diagnostic marker of AOSD. This paper supports the targeting of this cytokine as a possible therapeutic option in AOSD. PMID:22762008
Bidirectional Prospective Associations Between Cardiac Autonomic Activity and Inflammatory Markers.
Hu, Mandy Xian; Lamers, Femke; Neijts, Melanie; Willemsen, Gonneke; de Geus, Eco J C; Penninx, Brenda W J H
2018-06-01
Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic measures and inflammatory markers. Analyses were conducted with baseline (n = 2823), 2-year (n = 2099), and 6-year (n = 1774) data from the Netherlands Study of Depression and Anxiety. To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time, and work) and inflammation were conducted in two data sets from the Netherlands Twin Register measured for 4.9 years (n = 356) and 5.4 years (n = 472). Autonomic nervous system measures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive protein (CRP) and interleukin (IL)-6. The Netherlands Study of Depression and Anxiety results showed that higher HR and lower RSA were cross-sectionally significantly associated with higher inflammatory levels. Higher HR predicted higher levels of CRP (B = .065, p < .001) and IL-6 (B = .036, p = .014) at follow-up. Higher CRP levels predicted lower RSA (B = -.024, p = .048) at follow-up. The Netherlands Twin Register results confirmed that higher HR was associated with higher CRP and IL-6 levels 4.9 years later. Higher IL-6 levels predicted higher HR and lower RSA at follow-up. Autonomic imbalance is associated with higher levels of inflammation. Independent data from two studies converge in evidence that higher HR predicts subsequent higher levels of CRP and IL-6. Inflammatory markers may also predict future ANS activity, but evidence for this was less consistent.
Mathieu, Yann; Gelhaye, Eric; Dumarçay, Stéphane; Gérardin, Philippe; Harvengt, Luc; Buée, Marc
2013-02-15
The dead wood and forest soils are sources of diversity and under-explored fungal strains with biotechnological potential, which require to be studied. Numerous enzymatic tests have been proposed to investigate the functional potential of the soil microbial communities or to test the functional abilities of fungal strains. Nevertheless, the diversity of these functional markers and their relevance in environmental studies or biotechnological screening does still have not been demonstrated. In this work, we assessed ten different extracellular enzymatic activities involved in the wood decaying process including β-etherase that specifically cleaves the β-aryl ether linkages in the lignin polymer. For this purpose, a collection of 26 fungal strains, distributed within three ecological groups (white, brown and soft rot fungi), has been used. Among the ten potential functional markers, the combinatorial use of only six of them allowed separation between the group of white and soft rot fungi from the brown rot fungi. Moreover, our results suggest that extracellular β-etherase is a rare and dispensable activity among the wood decay fungi. Finally, we propose that this set of markers could be useful for the analysis of fungal communities in functional and environmental studies, and for the selection of strains with biotechnological interests. Copyright © 2012 Elsevier B.V. All rights reserved.
Smilic, Tanja N; Novakovic, Tatjana R; Markovic-Jovanovic, Snezana R; Smilic, Ljiljana L J; Mitic, Javorka S; Radunovic, Miodrag L
2017-11-02
In general, markers of bone formation and markers of bone resorption are changing synergistically, so the monitoring of any osteoclastic and any osteoblastic marker should reflect the rate of bone transformation. The aim of the study is to monitor the bone metabolism markers in postmenopausal women with osteoporosis and osteopenia along with the variations caused by the effects of bisphosphonate therapy. The study involved 55 women of average age of 57.95 years, with osteopenia or osteoporosis. The patients with osteoporosis were treated with bisphosphonates (75 mg once a week); the laboratory tests were performed before the treatment and 6 months later. Patients with osteopenia were evaluated at the first assessment and 6 months later. The tests included bone densitometry, dual-energy X-ray absorptiometry, osteocalcin, alkaline phosphatase, collagen 1 N-terminal pro-peptide (P1NP), and beta C telopeptide of type I collagen (CTX). The mean T-score was -2.80 ± 0.63 before therapy and -2.64 ± 0.45 6 months later (p < 0.001). Women with osteoporosis had elevated levels of osteocalcin and P1NP at the first assessment, whereas the alkaline phosphatase level did not change with the treatment. After the introduction of antiresorptive therapy, the levels of osteocalcin and P1NP significantly decreased (p < 0.001). In the group with osteopenia, the biochemical markers activity were increased in both assessments. In patients with osteoporosis, Beta-CTX was increased in the first evaluation, and decreased after treatment (p = 0.001). The results indicate that the assessment of biochemical markers of bone metabolism show excellent results in the assessment of prognosis, monitoring the course and the response to various treatment regimens of osteoporosis and evince strong correlation with standard densitometry and dual-energy X-ray absorptiometry procedures. P1NP and CTX show better diagnostic applicability compared with osteocalcin and alkaline phosphatase
Microglial activation is a pharmacologically specific marker for the neurotoxic amphetamines.
Thomas, David M; Dowgiert, Jennifer; Geddes, Timothy J; Francescutti-Verbeem, Dina; Liu, Xiuli; Kuhn, Donald M
2004-09-09
Neurotoxic amphetamines cause damage to monoamine nerve terminals of the striatum by unknown mechanisms. Microglial activation contributes to the neuronal damage that accompanies injury, disease, and inflammation, but a role for these cells in amphetamine-induced neurotoxicity has received little attention. We show presently that D-methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), D-amphetamine, and p-chloroamphetamine, each of which has been linked to dopamine (DA) or serotonin nerve terminal damage, result in microglial activation in the striatum. The non-neurotoxic amphetamines l-methamphetamine, fenfluramine, and DOI do not have this effect. All drugs that cause microglial activation also increase expression of glial fibrillary acidic protein (GFAP). At a minimum, microglial activation serves as a pharmacologically specific marker for striatal nerve terminal damage resulting only from those amphetamines that exert neurotoxicity. Because microglia are known to produce many of the reactive species (e.g., nitric oxide, superoxide, cytokines) that mediate the neurotoxicity of the amphetamine-class of drugs, their activation could represent an early and essential event in the neurotoxic cascade associated with high-dose amphetamine intoxication.
NP001 regulation of macrophage activation markers in ALS: A phase I clinical and biomarker study
MILLER, ROBERT G.; ZHANG, RONGZHEN; BLOCK, GILBERT; KATZ, JONATHAN; BAROHN, RICHARD; KASARSKIS, EDWARD; FORSHEW, DALLAS; GOPALAKRISHNAN, VIDHYA; MCGRATH, MICHAEL S.
2017-01-01
This is a phase I, placebo-controlled, single ascending dose safety and tolerability study of NP001 in patients with ALS. NP001 is a novel regulator of inflammatory macrophages and monocytes. As ALS progression is thought to be related to neuroinflammation, an additional objective of the study was to assess the effects of NP001 administration on monocyte activation markers. Thirty-two ALS patients were enrolled and received either placebo (eight) or one of four (six at each dose) ascending single i.v. doses (0.2, 0.8, 1.6 and 3.2 mg/kg NP001). Patients were monitored for safety, and blood monocyte immune activation markers CD16 and HLA-DR were assessed pre- and 24 h post-dosing. Changes from baseline were calculated. Results showed that NP001 was generally safe and well tolerated. Importantly, a single dose of NP001 caused a dose-dependent reduction in expression of monocyte CD16, a marker of monocyte activation/inflammation. Additionally, monocyte HLA-DR expression was also decreased in those patients with elevated values at baseline. In conclusion, these data indicate that NP001 has an acute effect on inflammatory monocytes in ALS patient blood. The potential for modulation of inflammation in the context of ALS disease progression will require further study with long-term follow-up. PMID:25192333
Use of DNA markers in forest tree improvement research
D.B. Neale; M.E. Devey; K.D. Jermstad; M.R. Ahuja; M.C. Alosi; K.A. Marshall
1992-01-01
DNA markers are rapidly being developed for forest trees. The most important markers are restriction fragment length polymorphisms (RFLPs), polymerase chain reaction- (PCR) based markers such as random amplified polymorphic DNA (RAPD), and fingerprinting markers. DNA markers can supplement isozyme markers for monitoring tree improvement activities such as; estimating...
Adenosine Deaminase activity and HLA-DRB as diagnostic markers for Rheumatoid Arthritis.
Valadbeigi, Shirin; Ebrahimi-Rad, Mina; Khatami, Shohreh; Akhbari, Hadi; Saghiri, Reza
2018-04-05
Rheumatoid Arthritis (RA) is a chronic multi systemic disorder with the unclarified ethiopathology. Although several markers have been presented for recognition of RA, but none of them has been specific. New markers such as HLA typing and activity of Adenosine deaminase (ADA) isoenzymes could be useful and specific. The aim of this study is to evaluate the pattern of ADA isoenzymes activity and HLA typing in both RA patients and healthy cases. Blood samples were collected from 55 RA patients and 60 healthy subjects, over a period of 6 months. Levels of C-reactive protein (CRP), rheumatoid factor (RF) and ADA (ADA1, ADA2, total ADA) were measured using AVITEX kit and HITACHI Auto Analyzer. In addition, HLA-DRB1*1,*04 and *010 was detected using PCR-SSP. ADA activity, particularly ADA2 level, was significantly higher among RA group (P<0.05). The concentrations of tADA in patients with RF and CRP positive were significantly higher (P <0.05). The allele prevalence of DRB1*10 and *01 was significantly higher in RA patients (8.3% and 13.1%, respectively) compared with control group (2.51% and 5.5%, respectively) (P <0.05). Calculated sensitivity and specificity for diagnostic tests in this study are listed as: CRP (75%), RF (80%), ADA (84%) and RF (90%), ADA (83%), CRP (72%), respectively. Increase tADA level and the frequency of DRB1*010 and *01 caused to susceptibility to RA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Blood–brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV
Yilmaz, Aylin; Hagberg, Lars; Zetterberg, Henrik; Nilsson, Staffan; Brew, Bruce J.; Fuchs, Dietmar; Price, Richard W.; Gisslén, Magnus
2016-01-01
Objective: Although blood–brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined. Methods: BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART). Results: The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis. Conclusions: BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals. PMID:27868081
Kosek, Margaret; Haque, Rashidul; Lima, Aldo; Babji, Sudhir; Shrestha, Sanjaya; Qureshi, Shahida; Amidou, Samie; Mduma, Estomih; Lee, Gwenyth; Yori, Pablo Peñataro; Guerrant, Richard L.; Bhutta, Zulfiqar; Mason, Carl; Kang, Gagandeep; Kabir, Mamun; Amour, Caroline; Bessong, Pascal; Turab, Ali; Seidman, Jessica; Olortegui, Maribel Paredes; Quetz, Josiane; Lang, Dennis; Gratz, Jean; Miller, Mark; Gottlieb, Michael
2013-01-01
Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrheal illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood. PMID:23185075
Brief Report: Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis.
Tito, Raul Y; Cypers, Heleen; Joossens, Marie; Varkas, Gaëlle; Van Praet, Liesbet; Glorieus, Elien; Van den Bosch, Filip; De Vos, Martine; Raes, Jeroen; Elewaut, Dirk
2017-01-01
Dysbiosis of the intestinal microbiota has been widely established in inflammatory bowel disease (IBD). There is significant clinical and genetic overlap between spondyloarthritis (SpA) and IBD, and up to 50% of all patients with SpA exhibit microscopic signs of bowel inflammation, often bearing particular resemblance to early Crohn's disease, a subtype of IBD. This study was undertaken to assess the relationship between intestinal microbial composition, gut histology, and disease activity markers in SpA. Gene analysis by 16S ribosomal RNA amplicon sequencing was used to compare the microbial composition in ileal and colonic biopsy specimens from 27 patients with SpA (14 with microscopic bowel inflammation, 13 without) and 15 healthy control subjects (ileal samples from all 15 subjects and colonic samples from 6). Spearman's rank correlation tests were used to assess correlations of the microbial composition with disease activity measures. The intestinal inflammation status (histologically normal versus acute or chronic inflammation) was strongly associated with the mucosal microbiota profile of patients with SpA. In inflamed biopsy tissue, the detected bacterial community composition clustered separately from that in noninflamed biopsy tissue (P < 0.05 by permutational multivariate analysis of variance, using hierarchical clustering on Bray-Curtis distances). Interestingly, abundance of the genus Dialister was found to be positively correlated with the Ankylosing Spondylitis Disease Activity Score (Spearman's rho = 0.62, false discovery rate-corrected q < 0.01). This finding was further supported by the low frequency of Dialister observed in noninflamed ileal and colonic biopsy tissue from patients with SpA and healthy controls. These findings demonstrate a significant difference in the intestinal microbial composition in patients with SpA who have microscopic gut inflammation compared to those without microscopic gut inflammation. Moreover, Dialister
PD-L1 is an activation-independent marker of brown adipocytes.
Ingram, Jessica R; Dougan, Michael; Rashidian, Mohammad; Knoll, Marko; Keliher, Edmund J; Garrett, Sarah; Garforth, Scott; Blomberg, Olga S; Espinosa, Camilo; Bhan, Atul; Almo, Steven C; Weissleder, Ralph; Lodish, Harvey; Dougan, Stephanie K; Ploegh, Hidde L
2017-09-21
Programmed death ligand 1 (PD-L1) is expressed on a number of immune and cancer cells, where it can downregulate antitumor immune responses. Its expression has been linked to metabolic changes in these cells. Here we develop a radiolabeled camelid single-domain antibody (anti-PD-L1 VHH) to track PD-L1 expression by immuno-positron emission tomography (PET). PET-CT imaging shows a robust and specific PD-L1 signal in brown adipose tissue (BAT). We confirm expression of PD-L1 on brown adipocytes and demonstrate that signal intensity does not change in response to cold exposure or β-adrenergic activation. This is the first robust method of visualizing murine brown fat independent of its activation state.Current approaches to visualise brown adipose tissue (BAT) rely primarily on markers that reflect its metabolic activity. Here, the authors show that PD-L1 is expressed on brown adipocytes, does not change upon BAT activation, and that BAT volume in mice can be measured by PET-CT with a radiolabeled anti-PD-L1 antibody.
Transcription Factor Activities Enhance Markers of Drug Sensitivity in Cancer.
Garcia-Alonso, Luz; Iorio, Francesco; Matchan, Angela; Fonseca, Nuno; Jaaks, Patricia; Peat, Gareth; Pignatelli, Miguel; Falcone, Fiammetta; Benes, Cyril H; Dunham, Ian; Bignell, Graham; McDade, Simon S; Garnett, Mathew J; Saez-Rodriguez, Julio
2018-02-01
Transcriptional dysregulation induced by aberrant transcription factors (TF) is a key feature of cancer, but its global influence on drug sensitivity has not been examined. Here, we infer the transcriptional activity of 127 TFs through analysis of RNA-seq gene expression data newly generated for 448 cancer cell lines, combined with publicly available datasets to survey a total of 1,056 cancer cell lines and 9,250 primary tumors. Predicted TF activities are supported by their agreement with independent shRNA essentiality profiles and homozygous gene deletions, and recapitulate mutant-specific mechanisms of transcriptional dysregulation in cancer. By analyzing cell line responses to 265 compounds, we uncovered numerous TFs whose activity interacts with anticancer drugs. Importantly, combining existing pharmacogenomic markers with TF activities often improves the stratification of cell lines in response to drug treatment. Our results, which can be queried freely at dorothea.opentargets.io, offer a broad foundation for discovering opportunities to refine personalized cancer therapies. Significance: Systematic analysis of transcriptional dysregulation in cancer cell lines and patient tumor specimens offers a publicly searchable foundation to discover new opportunities to refine personalized cancer therapies. Cancer Res; 78(3); 769-80. ©2017 AACR . ©2017 American Association for Cancer Research.
Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP.
Elkord, Eyad; Abd Al Samid, May; Chaudhary, Belal
2015-08-21
Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4+FoxP3- T cells expressing Helios (FoxP3-Helios+) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4+Helios+ T cells regardless of FoxP3 expression (FoxP3+/-Helios+). We show that CD4+GARP+/-LAP+ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3+Helios+ Tregs proliferate in vitro significantly less than FoxP3+Helios- Tregs upon TCR stimulation. Unlike FoxP3+Helios- Tregs, FoxP3+Helios+ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3+Helios+ Tregs have more suppressive characteristics, compared with FoxP3+Helios- Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3+Helios+ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction.
Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP
Elkord, Eyad; Abd Al Samid, May; Chaudhary, Belal
2015-01-01
Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4+FoxP3− T cells expressing Helios (FoxP3−Helios+) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4+Helios+ T cells regardless of FoxP3 expression (FoxP3+/−Helios+). We show that CD4+GARP+/−LAP+ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3+Helios+ Tregs proliferate in vitro significantly less than FoxP3+Helios− Tregs upon TCR stimulation. Unlike FoxP3+Helios− Tregs, FoxP3+Helios+ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3+Helios+ Tregs have more suppressive characteristics, compared with FoxP3+Helios− Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3+Helios+ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction. PMID:26343373
Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder.
Sublette, M Elizabeth; Galfalvy, Hanga C; Fuchs, Dietmar; Lapidus, Manana; Grunebaum, Michael F; Oquendo, Maria A; Mann, J John; Postolache, Teodor T
2011-08-01
Inflammation has been linked to depression and suicide risk. One inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP). Recent data suggest that KYN increases in cerebrospinal fluid (CSF) are associated with depressive symptoms secondary to immune activation. KYN may alter dopaminergic and glutamatergic tone, thereby contributing to increased arousal, agitation and impulsivity - important risk factors in suicide. We hypothesized that patients with major depressive disorder (MDD) and a history of suicide attempt would have higher levels of KYN than depressed nonattempters, who in turn would have higher levels than healthy volunteers. Plasma KYN, TRP, and neopterin were assayed by high performance liquid chromatography in three groups: healthy volunteers (n=31) and patients with MDD with (n=14) and without (n=16) history of suicide attempt. Analysis of variance tested for group differences in KYN levels. KYN levels differed across groups (F=4.03, df=(2,58), and p=0.023): a priori planned contrasts showed that KYN was higher in the MDD suicide attempter subgroup compared with MDD non-attempters (t=2.105, df=58, and p=0.040), who did not differ from healthy volunteers (t=0.418, df=58, and p=0.677). In post hoc testing, KYN but not TRP was associated with attempt status, and only suicide attempters exhibited a positive correlation of the cytokine activation marker neopterin with the KYN:TRP ratio, suggesting that KYN production may be influenced by inflammatory processes among suicide attempters. These preliminary results suggest that KYN and related molecular pathways may be implicated in the pathophysiology of suicidal behavior. Copyright © 2011. Published by Elsevier Inc.
30 CFR 817.11 - Signs and markers.
Code of Federal Regulations, 2011 CFR
2011-07-01
... identification signs. (1) Identification signs shall be displayed at each point of access from public roads to... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Signs and markers. 817.11 Section 817.11... ACTIVITIES § 817.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall...
30 CFR 817.11 - Signs and markers.
Code of Federal Regulations, 2014 CFR
2014-07-01
... identification signs. (1) Identification signs shall be displayed at each point of access from public roads to... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Signs and markers. 817.11 Section 817.11... ACTIVITIES § 817.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall...
30 CFR 817.11 - Signs and markers.
Code of Federal Regulations, 2010 CFR
2010-07-01
... identification signs. (1) Identification signs shall be displayed at each point of access from public roads to... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Signs and markers. 817.11 Section 817.11... ACTIVITIES § 817.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall...
30 CFR 817.11 - Signs and markers.
Code of Federal Regulations, 2012 CFR
2012-07-01
... identification signs. (1) Identification signs shall be displayed at each point of access from public roads to... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Signs and markers. 817.11 Section 817.11... ACTIVITIES § 817.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall...
30 CFR 817.11 - Signs and markers.
Code of Federal Regulations, 2013 CFR
2013-07-01
... identification signs. (1) Identification signs shall be displayed at each point of access from public roads to... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Signs and markers. 817.11 Section 817.11... ACTIVITIES § 817.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall...
Yeh, T S; Cheng, A J; Chen, T C; Jan, Y Y; Hwang, T L; Jeng, L B; Chen, M F; Wang, T C
1999-12-01
Pancreatic serous cystadenoma, mucinous cystic neoplasms, ductal adenocarcinoma with cystic change, and pseudocysts are a spectrum of pancreatic cystic lesions. Their management strategy and prognosis are extremely diverse. Imaging study, cytology, and analysis of the tumor markers of cyst fluid are not always reliable in differentiation of these disease entities. Fifteen patients with pancreatic cystic neoplasms (including six mucinous cystadenocarcinomas, two mucinous cystic neoplasms with borderline malignancy, two mucinous cystadenomas, and five serous cystadenomas), 4 patients with pancreatic ductal adenocarcinomas with cystic change, and 10 patients with pseudocysts were studied. Echo-guided or computed tomography-guided biopsies of pancreatic cystic lesions and their normal counterparts were conducted on all patients prior to operation or other management. The specimens were assayed for telomerase activity by using TRAP (telomere repeat amplification protocol). The level of telomerase activity in each specimen was semiquantitated as strong, moderate, weak, and none. The final diagnoses were made from histopathological examination of surgically resected or biopsied specimens. The efficacy of telomerase activity as a tumor marker to predict malignancy of pancreatic cystic lesions was evaluated. Three of the four pancreatic ductal adenocarcinomas with cystic change had strong or moderate telomerase activity; four of the six mucinous cystadenocarcinomas had moderate or weak telomerase activity; one of the two mucinous cystadenomas with borderline malignancy had weak telomerase activity; and none of their normal counterparts had detectable telomerase activity. In contrast, none of the two mucinous cystadenomas, five serous cystadenomas, and 10 pseudocysts had detectable telomerase activity. Based on these results, the sensitivity of telomerase activity for prediction of malignancy or premalignancy of pancreatic cystic lesions was 67%, the specificity was 100
Jain, Ashali; Khalid, Maria; Qureshi, Muhammad M; Georgian-Smith, Dianne; Kaplan, Jonah A; Buch, Karen; Grinstaff, Mark W; Hirsch, Ariel E; Hines, Neely L; Anderson, Stephan W; Gallagher, Katherine M; Bates, David D B; Bloch, B Nicolas
2017-11-01
To evaluate breast biopsy marker migration in stereotactic core needle biopsy procedures and identify contributing factors. This retrospective study analyzed 268 stereotactic biopsy markers placed in 263 consecutive patients undergoing stereotactic biopsies using 9G vacuum-assisted devices from August 2010-July 2013. Mammograms were reviewed and factors contributing to marker migration were evaluated. Basic descriptive statistics were calculated and comparisons were performed based on radiographically-confirmed marker migration. Of the 268 placed stereotactic biopsy markers, 35 (13.1%) migrated ≥1 cm from their biopsy cavity. Range: 1-6 cm; mean (± SD): 2.35 ± 1.22 cm. Of the 35 migrated biopsy markers, 9 (25.7%) migrated ≥3.5 cm. Patient age, biopsy pathology, number of cores, and left versus right breast were not associated with migration status (P> 0.10). Global fatty breast density (P= 0.025) and biopsy in the inner region of breast (P = 0.031) were associated with marker migration. Superior biopsy approach (P= 0.025), locally heterogeneous breast density, and t-shaped biopsy markers (P= 0.035) were significant for no marker migration. Multiple factors were found to influence marker migration. An overall migration rate of 13% supports endeavors of research groups actively developing new biopsy marker designs for improved resistance to migration. • Breast biopsy marker migration is documented in 13% of 268 procedures. • Marker migration is affected by physical, biological, and pathological factors. • Breast density, marker shape, needle approach etc. affect migration. • Study demonstrates marker migration prevalence; marker design improvements are needed.
Barić Rafaj, R; Kuleš, J; Marinculić, A; Tvarijonaviciute, A; Ceron, J; Mihaljević, Ž; Tumpa, A; Mrljak, V
2017-01-06
Obesity is one of the most prevalent health problems in the canine population. While haemostatic parameters and markers of endothelial function have been evaluated in various disease conditions in dogs, there are no studies of these markers in canine obesity. This study was designed to evaluate the effect of naturally gained weight excess and obesity on inflammatory, hemostatic and endothelial biomarkers in dogs. A total of 37 overweight and obese dogs were compared with 28 normal weight dogs. Overweight and obese dogs had significantly elevated concentrations of serum interleukin-6 (IL-6) and C-reactive protein (hsCRP). Number of platelets, activity of factor X and factor VII were significantly higher, while activated partial thromboplastine time (aPTT) and soluble plasminogen activator receptor (suPAR) were significantly decreased. Statistical analysis of high mobility group box - 1 protein (HMGB-1), soluble intercellular adhesive molecule -1 (sICAM-1) and plasminogen activator inhibitor type 1 (PAI-1) concentrations did not show significant differences between the total overweight and obese group and the normal weight group of dogs. Analytical changes in the dogs in our study reflects that weight excess in dogs can be associated with a chronic low degree of inflammation and a hypercoagulable state, where primary and secondary hemostasis are both affected. However obesity is not associated with impairment of endothelial function in dogs.
Almeida, Jorge R C; Versace, Amelia; Hassel, Stefanie; Kupfer, David J; Phillips, Mary L
2010-03-01
Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. The BDd-relative to HC, BDr, and MDD-showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity. Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Kuryliszyn-Moskal, A; Ciolkiewicz, M; Klimiuk, P A; Sierakowski, S
2009-01-01
To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p < 0.001) as well as with immunosuppressive therapy (p < 0.01). Significant differences were found in VEGF (p < 0.001), ET-1 (p < 0.001), sE-selectin (p < 0.01), and sTM (p < 0.001) serum concentrations between SLE patients with a capillaroscopic score > 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.
Monoamine oxidase A (MAO-A): a signature marker of alternatively activated monocytes/macrophages
Cathcart, Martha K.; Bhattacharjee, Ashish
2015-01-01
Monocytes/macrophages are versatile cells centrally involved in host defense and immunity. Th1 cytokines induce a classical activation program in monocytes/macrophages leading to a proinflammatory M1 macrophage phenotype while Th2 cytokines IL-4 and IL-13 promote monocyte differentiation into an alternatively activated, anti-inflammatory M2 macrophage phenotype. Although monoamine oxidase A (MAO-A) is primarily known for its action in the nervous system, several recent studies have identified MAO-A as a signature marker of alternative activation of monocytes/macrophages. In this brief review we explore the signaling pathways/molecules that regulate MAO-A expression in alternatively activated monocytes/macrophages. We further discuss the contribution of MAO-A to the resolution of inflammation and identify potential therapeutic targets for controlling inflammation. Altogether this review provides deeper insight into the role of MAO-A in alternative activation of monocytes/macrophages and their participation in the inflammatory response. PMID:26052543
Monoamine oxidase A (MAO-A): a signature marker of alternatively activated monocytes/macrophages.
Cathcart, Martha K; Bhattacharjee, Ashish
Monocytes/macrophages are versatile cells centrally involved in host defense and immunity. Th1 cytokines induce a classical activation program in monocytes/macrophages leading to a proinflammatory M1 macrophage phenotype while Th2 cytokines IL-4 and IL-13 promote monocyte differentiation into an alternatively activated, anti-inflammatory M2 macrophage phenotype. Although monoamine oxidase A (MAO-A) is primarily known for its action in the nervous system, several recent studies have identified MAO-A as a signature marker of alternative activation of monocytes/macrophages. In this brief review we explore the signaling pathways/molecules that regulate MAO-A expression in alternatively activated monocytes/macrophages. We further discuss the contribution of MAO-A to the resolution of inflammation and identify potential therapeutic targets for controlling inflammation. Altogether this review provides deeper insight into the role of MAO-A in alternative activation of monocytes/macrophages and their participation in the inflammatory response.
Surekha, T; Himabindu, Y; Sriharibabu, M; Pandey, Anil Kumar
2014-01-01
Physical inactivity is a leading risk factor for overweight and obesity in the society. Prevalence of overweight and obesity in the reproductive age group women not only affects maternal health but also the health of the off spring. Infertility is a common problem in India affecting 13-19 million people at any given time. Even though it is not life threatening, infertility causes intense mental agony and trauma that can only be best described by infertile couples themselves. Infertility is more common in overweight and obese individuals compared to normal weight individuals. Decreasing ovarian reserve is an important factor for infertility in women. This study examined the impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women. The observations made in this study reveal that physical activity improves ovarian reserve markers in all reproductive age women but this improvement is more distinct and statistically significant in overweight and obese women compared to normal weight women.
Chi, Shuhong; Yu, Yunxia; Shi, Juan; Zhang, Yurong; Yang, Jijuan; Yang, Lijuan; Liu, Xiaoming
2015-01-01
Objective. An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the diagnostic values of circulating autoantibodies to C1q alone or in combination with other markers for accessing active SLE and LN were evaluated. Methods. The diagnostic value of anti-C1q autoantibodies for identification of patients with active SLE disease and LN was evaluated by analyzing the level of anti-C1q antibodies in sera from 95 SLE patients, 40 non-SLE patients, and 34 healthy cohorts. Results. The prevalence of anti-C1q antibodies was significantly higher in patients with SLE (50/95, 52.6%), active SLE (40/51, 78.4%), and LN (30/35, 85.7%) in comparison with non-SLE patient controls, patients with inactive SLE, and non-LN, respectively. A combination of anti-C1q with anti-dsDNA and/or levels of complements C3 and C4 exhibited an increased specificity but a decreased sensitivity for identification of patients with active SLE and LN diseases relative to each of these markers alone. Conclusion. Anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that it may be a reliable serological marker for identification of SLE patients with active LN and active SLE disease. PMID:26549923
Maes, Michael; Ringel, Karl; Kubera, Marta; Anderson, George; Morris, Gerwyn; Galecki, Piotr; Geffard, Michel
2013-09-05
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation. We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale). The incidence of positive autoimmune activity against 5-HT was significantly higher (p<0.001) in ME/CFS (61.5%) than in patients with CF (13.9%) and controls (5.7%). ME/CFS patients with 5-HT autoimmune activity displayed higher TNFα, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. Anti-5-HT antibody positivity was significantly associated with increased scores on hyperalgesia, fatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise. The results show that, in ME/CFS, increased 5-HT autoimmune activity is associated with activation of immuno-inflammatory pathways and increased bacterial translocation, factors which are known to play a role in the onset of autoimmune reactions. 5-HT autoimmune activity could play a role in the pathophysiology of ME/CFS and the onset of physio-somatic symptoms. These results provide mechanistic support for the notion that ME/CFS is a neuro-immune disorder. Copyright © 2013
Ciołkiewicz, Mariusz; Kuryliszyn-Moskal, Anna; Klimiuk, Piotr Adrian
2010-02-01
The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p < 0.01) and sE-selectin (r = 0.274, p < 0.05) serum levels as well as between sTM and ET-1 (r = 0.273, p < 0.05) serum concentrations. We noticed also positive correlation between VEGF (r = 0.224, p < 0.05) and ET-1 (r = 0.471, p < 0.001) serum levels and disease activity, and also between VEGF serum concentration and grade of morphological changes observed by nailfold capillaroscopy (r = 0.458, p < 0.001). There was also positive correlation between capillaroscopic score and disease activity (r = 0.339, p < 0.01). Our data suggest that correlation between VEGF and both ET-1 and E-selectin serum levels as well as between sTM and ET-1 serum concentrations may reflect their participation in the pathogenesis of SLE. VEGF seems to reflect changes in microcirculation in the course of SLE, visualised by nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.
Foschi, F G; Gramenzi, A; Castelli, E; Cursaro, C; Pagani, S; Margotti, M; D'Errico, A; Andreone, P; Stefanini, G F; Bernardi, M
2000-06-01
In the present study, high levels of CD30s, a glycoprotein preferentially expressed and released by T lymphocytes producing Th(2)-type cytokines, were seen in the sera of patients with chronic hepatitis C, and a correlation with histological activity of the disease was found. CD30s levels were assayed in the sera of 29 HCV RNA-positive patients with histologically proven chronic active hepatitis and in 30 healthy blood donors. Thirteen of 29 (45%) HCV patients had CD30s serum levels above the normal range (>20 U/ml). Mean CD30s serum levels were significantly higher in HCV patients than in controls (P<0.0005). A positive correlation was found between serum CD30s levels and both the histological activity index (r=0.59, P=0.001) and ALT serum levels (r=0.5; P=0.006). The raised CD30s level found in more severe HCV liver disease indirectly suggests activation and expansion of Th(2)cells. CD30s levels could represent a useful surrogate marker of activity in chronic HCV infections. Copyright 2000 Academic Press.
Hamer, Mark; Sabia, Severine; Batty, G David; Shipley, Martin J; Tabák, Adam G; Singh-Manoux, Archana; Kivimaki, Mika
2012-08-21
Inflammatory processes are putative mechanisms underlying the cardioprotective effects of physical activity. An inverse association between physical activity and inflammation has been demonstrated, but no long-term prospective data are available. We therefore examined the association between physical activity and inflammatory markers over a 10-year follow-up period. Participants were 4289 men and women (mean age, 49.2 years) from the Whitehall II cohort study. Self-reported physical activity and inflammatory markers (serum high-sensitivity C-reactive protein and interleukin-6) were measured at baseline (1991) and follow-up (2002). Forty-nine percent of the participants adhered to standard physical activity recommendations for cardiovascular health (2.5 h/wk moderate to vigorous physical activity) across all assessments. Physically active participants at baseline had lower C-reactive protein and interleukin-6 levels, and this difference remained stable over time. Compared with participants who rarely adhered to physical activity guidelines over the 10-year follow-up, the high-adherence group displayed lower log(e) C-reactive protein (β=-0.07; 95% confidence interval, -0.12 to -0.02) and log(e) interleukin-6 (β=-0.07; 95% confidence interval, -0.10 to -0.03) at follow-up after adjustment for a range of covariates. Compared with participants who remained stable, those who reported an increase in physical activity of at least 2.5 h/wk displayed lower log(e) C-reactive protein (β coefficient=-0.05; 95% confidence interval, -0.10 to -0.001) and log(e) interleukin-6 (β coefficient=-0.06; 95% confidence interval, -0.09 to -0.03) at follow-up. Regular physical activity is associated with lower markers of inflammation over 10 years of follow-up and thus may be important in preventing the proinflammatory state seen with aging.
Camarillo-Romero, Eneida; Dominguez-Garcia, Ma Victoria; Amaya-Chavez, Araceli; Camarillo-Romero, Maria del Socorro; Talavera-Piña, Juan; Huitron-Bravo, Gerardo; Majluf-Cruz, Abraham
2012-01-01
The metabolic syndrome (MetS) is a precursor of diabetes. Physical activity (PA) improves endothelial dysfunction and may benefit patients with MetS. Aims. To evaluate the effect of a physical activity (PA) program on markers of endothelial dysfunction and oxidative stress in adolescents with (MetS). Methods. We carried out a cohort study of 38 adolescents with and without MetS (18 females and 20 males). All participants completed a 3-month PA program. All variables of the MetS as well as markers of endothelial dysfunction and oxidative stress tests were evaluated. Results. Females with and without MetS showed significant differences for almost all components of the MetS, whereas males were significantly different in half of the components. After the PA program, components of the MetS were not different from baseline values except for HDL-C levels. Some baseline endothelial dysfunction markers were significantly different among adolescents with and without MetS; however, after the PA program, most of these markers significantly improved in subjects with and without MetS. Conclusion. PA improves the markers of endothelial dysfunction in adolescents with MetS although other changes in the components of the MetS were not observed. Perhaps the benefits of PA on all components of MetS would appear after a PA program with a longer duration. PMID:22888450
Zhu, Hui; Zhao, Teng; Liu, Jingyao
2018-06-01
Paraoxonase1 (PON1) is an antioxidant which confers antioxidant properties to high-density lipoprotein (HDL) and prevents low-density lipoprotein (LDL) oxidation. The purpose of this study was to evaluate the activities of PON1 and oxidative/antioxidative stress markers in acute cerebral infarction. In this study, 161 patients diagnosed with acute cerebral infarction and 161 gender- and age-matched healthy controls were recruited. Based on the clinicoradiological profiles, the patients were further classified into two groups: lacunar infarction group and large-artery atherosclerosis group. We measured the individual lipid status parameters, oxidative and antioxidative stress status parameters, and PON1 activity. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and oxidative stress parameters in patients with acute cerebral infarction were significantly higher than those in the normal controls (p < 0.05). High-density lipoprotein cholesterol (HDL-C) level, PON1 activity, superoxide dismutase (SOD) activity, and antioxidative stress parameters in patients were lower than in the normal controls (p < 0.05). Superoxide anion (O2-), malondialdehyde (MDA), and PON1 levels in the lacunar infarction group were lower than in the large-artery atherosclerosis group (p < 0.05). Oxidative stress markers and PON1 activity are sensitive indicators of acute cerebral infarction. Our findings suggest a severely impaired antioxidative protection mechanism in these patients. Our study provides new insights into the pathophysiological mechanisms of acute cerebral infarction, which may also provide new therapeutic targets for ischemic cerebrovascular diseases.
Time-course of changes in neuronal activity markers following iTBS-TMS of the rat neocortex.
Hoppenrath, Kathrin; Funke, Klaus
2013-03-01
In a rat model of transcranial magnetic stimulation we could recently show that intermittent theta-burst stimulation (iTBS) affects the neocortical expression of the immediate early gene products c-Fos and zif268 as well as that of the two glutamic acid decarboxylase isoforms GAD65 and GAD67 and that of the calcium-binding proteins calbindin (CB) and parvalbumin (PV), known as markers of excitatory and inhibitory activity. We now analyzed in more detail the time course of changes in the expression of these proteins at 10, 20, 40, 80 and 160min following a single block of iTBS consisting of 600 stimuli. Initial increase in c-Fos, zif268 and GAD65 (20min) signals transient activation of excitatory and inhibitory neurons, thereafter first followed by a decrease in markers of activity of inhibitory neurons (GAD67, PV, CB: 20-80min) and then by a late decrease in c-Fos and GAD65 expression (160min). The results demonstrate that one iTBS block may have an after-effect of at least two different phases, an early phase with increased neuronal activity (c-Fos, zif268) but also the likelihood of increased GABA-release (GAD65), followed by a late phase (>40min) of reduced neuronal activity in excitatory and inhibitory systems which may indicate a state of reduced excitability. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Frameworking memory and serotonergic markers.
Meneses, Alfredo
2017-07-26
The evidence for neural markers and memory is continuously being revised, and as evidence continues to accumulate, herein, we frame earlier and new evidence. Hence, in this work, the aim is to provide an appropriate conceptual framework of serotonergic markers associated with neural activity and memory. Serotonin (5-hydroxytryptamine [5-HT]) has multiple pharmacological tools, well-characterized downstream signaling in mammals' species, and established 5-HT neural markers showing new insights about memory functions and dysfunctions, including receptors (5-HT1A/1B/1D, 5-HT2A/2B/2C, and 5-HT3-7), transporter (serotonin transporter [SERT]) and volume transmission present in brain areas involved in memory. Bidirectional influence occurs between 5-HT markers and memory/amnesia. A growing number of researchers report that memory, amnesia, or forgetting modifies neural markers. Diverse approaches support the translatability of using neural markers and cerebral functions/dysfunctions, including memory formation and amnesia. At least, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors and SERT seem to be useful neural markers and therapeutic targets. Hence, several mechanisms cooperate to achieve synaptic plasticity or memory, including changes in the expression of neurotransmitter receptors and transporters.
Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike
2016-05-01
Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.
De Groote, Mary A; Sterling, David G; Hraha, Thomas; Russell, Theresa M; Green, Louis S; Wall, Kirsten; Kraemer, Stephan; Ostroff, Rachel; Janjic, Nebojsa; Ochsner, Urs A
2017-10-01
New non-sputum biomarker tests for active tuberculosis (TB) diagnostics are of the highest priority for global TB control. We performed in-depth proteomic analysis using the 4,000-plex SOMAscan assay on 1,470 serum samples from seven countries where TB is endemic. All samples were from patients with symptoms and signs suggestive of active pulmonary TB that were systematically confirmed or ruled out for TB by culture and clinical follow-up. HIV coinfection was present in 34% of samples, and 25% were sputum smear negative. Serum protein biomarkers were identified by stability selection using L1-regularized logistic regression and by Kolmogorov-Smirnov (KS) statistics. A naive Bayes classifier using six host response markers (HR6 model), including SYWC, kallistatin, complement C9, gelsolin, testican-2, and aldolase C, performed well in a training set (area under the sensitivity-specificity curve [AUC] of 0.94) and in a blinded verification set (AUC of 0.92) to distinguish TB and non-TB samples. Differential expression was also highly significant ( P < 10 -20 ) for previously described TB markers, such as IP-10, LBP, FCG3B, and TSP4, and for many novel proteins not previously associated with TB. Proteins with the largest median fold changes were SAA (serum amyloid protein A), NPS-PLA2 (secreted phospholipase A2), and CA6 (carbonic anhydrase 6). Target product profiles (TPPs) for a non-sputum biomarker test to diagnose active TB for treatment initiation (TPP#1) and for a community-based triage or referral test (TPP#2) have been published by the WHO. With 90% sensitivity and 80% specificity, the HR6 model fell short of TPP#1 but reached TPP#2 performance criteria. In conclusion, we identified and validated a six-marker signature for active TB that warrants diagnostic development on a patient-near platform. Copyright © 2017 De Groote et al.
De Groote, Mary A.; Sterling, David G.; Hraha, Thomas; Russell, Theresa M.; Green, Louis S.; Wall, Kirsten; Kraemer, Stephan; Ostroff, Rachel; Janjic, Nebojsa
2017-01-01
ABSTRACT New non-sputum biomarker tests for active tuberculosis (TB) diagnostics are of the highest priority for global TB control. We performed in-depth proteomic analysis using the 4,000-plex SOMAscan assay on 1,470 serum samples from seven countries where TB is endemic. All samples were from patients with symptoms and signs suggestive of active pulmonary TB that were systematically confirmed or ruled out for TB by culture and clinical follow-up. HIV coinfection was present in 34% of samples, and 25% were sputum smear negative. Serum protein biomarkers were identified by stability selection using L1-regularized logistic regression and by Kolmogorov-Smirnov (KS) statistics. A naive Bayes classifier using six host response markers (HR6 model), including SYWC, kallistatin, complement C9, gelsolin, testican-2, and aldolase C, performed well in a training set (area under the sensitivity-specificity curve [AUC] of 0.94) and in a blinded verification set (AUC of 0.92) to distinguish TB and non-TB samples. Differential expression was also highly significant (P < 10−20) for previously described TB markers, such as IP-10, LBP, FCG3B, and TSP4, and for many novel proteins not previously associated with TB. Proteins with the largest median fold changes were SAA (serum amyloid protein A), NPS-PLA2 (secreted phospholipase A2), and CA6 (carbonic anhydrase 6). Target product profiles (TPPs) for a non-sputum biomarker test to diagnose active TB for treatment initiation (TPP#1) and for a community-based triage or referral test (TPP#2) have been published by the WHO. With 90% sensitivity and 80% specificity, the HR6 model fell short of TPP#1 but reached TPP#2 performance criteria. In conclusion, we identified and validated a six-marker signature for active TB that warrants diagnostic development on a patient-near platform. PMID:28794177
Advances in marker-assisted breeding of sugarcane
USDA-ARS?s Scientific Manuscript database
Despite the challenges posed by sugarcane, geneticists and breeders have actively sought to use DNA marker technology to enhance breeding efforts. Markers have been used to explore taxonomy, estimate genetic diversity, and to develop unique molecular fingerprints. Numerous studies have been undertak...
Yang, Dong-Hoon; Yang, Suk-Kyun; Park, Sang Hyoung; Lee, Ho-Su; Boo, Sun-Jin; Park, Jae-Ho; Na, Soo Young; Jung, Kee Wook; Kim, Kyung-Jo; Ye, Byong Duk; Byeon, Jeong-Sik; Myung, Seung-Jae; Kim, Jin-Ho
2015-01-01
Background/Aims C-reactive protein (CRP) is a serologic activity marker in Crohn’s disease (CD), but it may be less useful in evaluating CD activity in ileal CD patients. We aimed to investigate the usefulness of CRP as a disease activity marker in CD according to disease location. Methods Korean CD patients in a single hospital were evaluated. Factors associated with elevated CRP concentration at the time of diagnosis of CD and the association between the physician’s prediction regarding upcoming surgery and the sites of the lesions directly related to surgery were analyzed. Results Of 435 CD patients, 25.7%, 6.9%, and 67.4% had ileal, colonic, and ileocolonic CD, respectively. Multivariate analysis revealed that an elevated erythrocyte sedimentation rate, reduced serum albumin, CD activity index (CDAI) >220, and ileocolonic/colonic location were associated with an elevated CRP level and that the CRP level was significantly correlated with the CDAI in all CD patients (γ=0.466, p<0.01). However, the correlation coefficient was dependent on the location, with values of 0.395, 0.456, and 0.527 in patients with an ileal, ileocolonic, and colonic disease location, respectively. Surgery for ileal lesions was less predictable than surgery for ileocolonic or colonic lesions during follow-up. Conclusions CRP is less useful as a disease activity marker in patients with ileal CD than those with ileocolonic or colonic CD. PMID:25170056
Braakman, I; Keij, J; Hardonk, M J; Meijer, D K; Groothuis, G M
1991-01-01
Periportal and perivenous hepatocytes are known to display various functional differences. In this study we present a new method to separate periportal and perivenous cells: after selectively loading zone 1 or zone 3 with the fluorescent label acridine orange in an antegrade or retrograde perfusion, respectively, we separated the isolated hepatocytes on a fluorescence-activated cell sorter. The common way to check on proper separation is to estimate activities of enzymes known to exhibit a heterogeneous acinar distribution. Using enzyme histochemistry, however, we found that already on short collagenase perfusion, some enzymes displayed a more shallow gradient than in vivo, making enzyme activities less suitable as zonal markers. We therefore used colloidal gold granules (17 nm) injected intravenously (2.5 mg) into the rat 2 to 3 hr before cell isolation. The gold is taken up predominantly by perivenous hepatocytes, probably because of the efficient removal of gold granules in zone 1 by competing Kupffer cells. We compared acridine orange fluorescence, presence of gold particles and activities of six marker enzymes, three biochemically and three histochemically determined. Acridine orange and gold both pointed to a high enrichment of the fractions, whereas most enzyme activities were more randomly distributed among the cells as a result of the isolation procedure. Our separation procedure yielded fractions highly enriched in either viable periportal or perivenous cells, both from one liver. The use of colloidal gold as a marker to monitor separation is a valuable alternative to the more risky estimation of enzyme activities.
Razmjou, Sahar; Bastard, Jean-Philippe; Doucet, Eric; Rabasa-Lhoret, Remi; Fellahi, Soraya; Lavoie, Jean-Marc; Prud'homme, Denis
2016-12-01
Menopausal transition is usually associated with changes in body composition and a decrease in physical activity energy expenditure. Adipose tissue, especially visceral fat, is an important source of inflammatory markers, which contributes to the development of a proinflammatory state. Conversely, high levels of physical activity and exercise have an anti-inflammatory effect. This study aimed to investigate the impact of menopausal transition and physical activity on inflammatory makers. One hundred two healthy premenopausal women participated in a 5-year longitudinal study. The present secondary analyses were performed on 58 participants with a full set of data (age: 49.6 ± 1.7 y; body mass index: 23.3 ± 2.4 kg/m). Measures included body composition, waist circumference, fasting glucose and insulin levels, insulin sensitivity, plasma lipid levels, cardiorespiratory fitness, physical activity energy expenditure, and inflammatory markers. Repeated measure analyses revealed, after the 5-year follow-up, significant increases in ferritin, interleukin-8 (IL-8), and soluble tumor necrosis factor-α receptor 1 and 2 (sTNFR1 and sTNFR2) (P < 0.001), and a significant decrease in serum high-sensitive C-reactive protein (P < 0.05). Positive correlations were observed between change (year 5 to baseline) in waist circumference and changes in high-sensitive C-reactive protein, orosomucoid (ORM), haptoglobin, and apolipoprotein B (ApoB) levels (0.26 ≤ r ≤ 0.34; P < 0.05), and between change in peripheral fat and changes in ORM, ApoB, sTNFR2 (0.28 ≤ r ≤ 0.39; P < 0.05). On the contrary, negative correlations were found between change in physical activity energy expenditure and changes in ORM as well as ApoB (r = -0.35 and r = -0.36, respectively; P < 0.05). No significant correlations were found between change in cardiorespiratory fitness, glucose, insulin, insulin sensitivity and changes in inflammatory markers. Multiple
Calcium-activated potassium channels as potential early markers of human cervical cancer
Ramírez, Ana; Vera, Eunice; Gamboa-Domínguez, Armando; Lambert, Paul; Gariglio, Patricio; Camacho, Javier
2018-01-01
Cervical cancer is a major cause of cancer-associated mortality in women in developing countries. Thus, novel early markers are required. Ion channels have gained great interest as tumor markers, including cervical cancer. The calcium-activated potassium channel KCNMA1 (subunit α-1 from subfamily M) has been associated with different malignancies, including tumors such as breast and ovarian cancer that are influenced by hormones. The KCNMA1 channel blocker iberiotoxin decreases the proliferation of HeLa cervical cancer cells. Nevertheless, KCNMA1 channel expression during cervical carcinogenesis remains elusive. Therefore, KCNMA1 expression was studied in cervical cancer development. FVB transgenic mice expressing the E7-oncogene of high-risk human papilloma virus, and non-transgenic mice were treated with estradiol-releasing pellets during 3 or 6 months to induce cervical lesions. Twenty-four human cervical biopsies from non-cancerous, low- or high-grade intraepithelial lesions, or cervical cancer were also studied. mRNA and protein expression was assessed by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively. Cervical dysplasia and carcinoma were observed only in the transgenic mice treated with estradiol for 3 and 6 months, respectively. Estradiol treatment increased KCNMA1 mRNA and protein expression in all groups; however, the highest levels were observed in the transgenic mice with carcinoma. KCNMA1 protein expression in the squamous cells of the transformation zone was observed only in the transgenic mice with cervical dysplasia or cancer. Human biopsies from non-cancerous cervix did not display KCNMA1 protein expression; in contrast, the majority of the tissues with cervical lesions (16/18) displayed KCNMA1 protein expression. The lowest channel immunostaining intensity was observed in biopsies from low-grade dysplasia and the strongest in the carcinoma tissues. These results suggest KCNMA1 channels as
Parker, Tony J.; Sampson, Dayle L.; Broszczak, Daniel; Chng, Yee L.; Carter, Shea L.; Leavesley, David I.; Parker, Anthony W.; Upton, Zee
2012-01-01
Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24 h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic/anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3/endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk/survival. PMID:22457785
Parker, Tony J; Sampson, Dayle L; Broszczak, Daniel; Chng, Yee L; Carter, Shea L; Leavesley, David I; Parker, Anthony W; Upton, Zee
2012-01-01
Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24 h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic/anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3/endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk/survival.
The Role of Apoptosis Associated Markers in Pathogenesis of Pulmonary Tuberculosis
2012-08-28
To Compare the Serum Apoptosis-associated Markers Between Patients With Active TB and Patients With LTBI; To Evaluate the Efficiency of Apoptosis-associated Markers to Differentiate Potential of Active TB From LTBI
Thiagarajan, Devi; O' Shea, Karen; Sreejit, Gopalkrishna; Ananthakrishnan, Radha; Quadri, Nosirudeen; Li, Qing; Schmidt, Ann Marie; Gabbay, Kenneth; Ramasamy, Ravichandran
2017-01-01
Aldose reductase (AR: human, AKR1B1; mouse, AKR1B3), the first enzyme in the polyol pathway, plays a key role in mediating myocardial ischemia/reperfusion (I/R) injury. In earlier studies, using transgenic mice broadly expressing human AKR1B1 to human-relevant levels, mice devoid of Akr1b3, and pharmacological inhibitors of AR, we demonstrated that AR is an important component of myocardial I/R injury and that inhibition of this enzyme protects the heart from I/R injury. In this study, our objective was to investigate if AR modulates the β-catenin pathway and consequent activation of mesenchymal markers during I/R in the heart. To test this premise, we used two different experimental models: in vivo, Akr1b3 null mice and wild type C57BL/6 mice (WT) were exposed to acute occlusion of the left anterior descending coronary artery (LAD) followed by recovery for 48 hours or 28 days, and ex-vivo, WT and Akr1b3 null murine hearts were perfused using the Langendorff technique (LT) and subjected to 30 min of global (zero-flow) ischemia followed by 60 min of reperfusion. Our in vivo results reveal reduced infarct size and improved functional recovery at 48 hours in mice devoid of Akr1b3 compared to WT mice. We demonstrate that the cardioprotection observed in Akr1b3 null mice was linked to acute activation of the β-catenin pathway and consequent activation of mesenchymal markers and genes linked to fibrotic remodeling. The increased activity of the β-catenin pathway at 48 hours of recovery post-LAD was not observed at 28 days post-infarction, thus indicating that the observed increase in β-catenin activity was transient in the mice hearts devoid of Akr1b3. In ex vivo studies, inhibition of β-catenin blocked the cardioprotection observed in Akr1b3 null mice hearts. Taken together, these data indicate that AR suppresses acute activation of β-catenin and, thereby, blocks consequent induction of mesenchymal markers during early reperfusion after myocardial ischemia
Circulating Markers of Vascular Injury and Angiogenesis in ANCA-Associated Vasculitis
Monach, Paul A; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Cuthbertson, David; Krischer, Jeffrey; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Ikle, David; Kallenberg, Cees GM; Langford, Carol A; Mueller, Mark; Seo, Philip; St.Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Gu, Yi-Zhong; Snyder, Ronald D; Merkel, Peter A
2011-01-01
Objective To identify biomarkers that distinguish between active ANCA-associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation. Methods Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV. 163 subjects enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Serum levels of E-selectin, ICAM-3, MMP1, MMP3, MMP9, P-selectin, thrombomodulin, and VEGF were measured at study screening (time of active disease) and at month 6. ESR and CRP levels had been measured at the time of the clinical visit. The primary outcome was the difference in marker level between screening and month 6 among patients in remission (BVAS/WG score of 0) at month 6. Results All subjects had severe active vasculitis (mean BVAS/WG score 8.6 +/− 3.2 SD) at screening. Among the 123 subjects clinically in remission at month 6, levels of all markers except E-selectin showed significant declines. MMP3 levels were also higher among the 23 subjects with active disease at month 6 than among the 123 subjects in remission. MMP3 levels correlated weakly with ESR and CRP. Conclusion Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers. PMID:21953143
Selective cortical VGLUT1 increase as a marker for antidepressant activity.
Moutsimilli, Larissa; Farley, Severine; Dumas, Sylvie; El Mestikawy, Salah; Giros, Bruno; Tzavara, Eleni T
2005-11-01
The two recently characterized vesicular glutamate transporters (VGLUT) presynaptically mark and differentiate two distinct excitatory neuronal populations and thus define a cortical and a subcortical glutamatergic system (VGLUT1 and VGLUT2 positive, respectively). These two systems might be differentially implicated in brain neuropathology. Still, little is known on the modalities of VGLUT1 and VGLUT2 regulations in response to pharmacological or physiological stimuli. Given the importance of cortical neuronal activity in psychosis we investigated VGLUT1 mRNA and protein expression in response to chronic treatment with commonly prescribed psychotropic medications. We show that agents with antidepressant activity, namely the antidepressants fluoxetine and desipramine, the atypical antipsychotic clozapine, and the mood stabilizer lithium increased VGLUT1 mRNA expression in neurons of the cerebral cortex and the hippocampus and in concert enhanced VGLUT1 protein expression in their projection fields. In contrast the typical antipsychotic haloperidol, the cognitive enhancers memantine and tacrine, and the anxiolytic diazepam were without effect. We suggest that VGLUT1 could be a useful marker for antidepressant activity. Furthermore, adaptive changes in VGLUT1 positive neurons could constitute a common functional endpoint for structurally unrelated antidepressants, representing promising antidepressant targets in tracking specificity, mechanism, and onset at action.
Hulmi, Juha J; Oliveira, Bernardo M; Silvennoinen, Mika; Hoogaars, Willem M H; Pasternack, Arja; Kainulainen, Heikki; Ritvos, Olli
2013-07-15
The importance of adequate levels of muscle size and function and physical activity is widely recognized. Myostatin/activin blocking increases skeletal muscle mass but may decrease muscle oxidative capacity and can thus be hypothesized to affect voluntary physical activity. Soluble activin receptor IIB (sActRIIB-Fc) was produced to block myostatin/activins. Modestly dystrophic mdx mice were injected with sActRIIB-Fc or PBS with or without voluntary wheel running exercise for 7 wk. Healthy mice served as controls. Running for 7 wk attenuated the sActRIIB-Fc-induced increase in body mass by decreasing fat mass. Running also enhanced/restored the markers of muscle oxidative capacity and autophagy in mdx mice to or above the levels of healthy mice. Voluntary running activity was decreased by sActRIIB-Fc during the first 3-4 wk correlating with increased body mass. Home cage physical activity of mice, quantified from the force plate signal, was decreased by sActRIIB-Fc the whole 7-wk treatment in sedentary mice. To understand what happens during the first weeks after sActRIIB-Fc administration, when mice are less active, healthy mice were injected with sActRIIB-Fc or PBS for 2 wk. During the sActRIIB-Fc-induced rapid 2-wk muscle growth period, oxidative capacity and autophagy were reduced, which may possibly explain the decreased running activity. These results show that increased muscle size and decreased markers of oxidative capacity and autophagy during the first weeks of myostatin/activin blocking are associated with decreased voluntary activity levels. Voluntary exercise in dystrophic mice enhances the markers of oxidative capacity and autophagy to or above the levels of healthy mice.
2011-02-15
M A J O R A R T I C L E High Dose Atorvastatin Decreases Cellular Markers of Immune Activation without Affecting HIV-1 RNA Levels: Results of a... atorvastatin on HIV-1 RNA (primary objective) and cellular markers of immune activation (secondary objective). HIV-infected individuals not receiving...antiretroviral therapy were randomized to receive either 8 weeks of atorvastatin (80 mg) or placebo daily. After a 4–6 week washout phase, participants
Gruber, Sabine; Omann, Markus; Rodrìguez, Carolina Escobar; Radebner, Theresa; Zeilinger, Susanne
2012-11-17
Species of the fungal genus Trichoderma are important industrial producers of cellulases and hemicellulases, but also widely used as biocontrol agents (BCAs) in agriculture. In the latter function Trichoderma species stimulate plant growth, induce plant defense and directly antagonize plant pathogenic fungi through their mycoparasitic capabilities. The recent release of the genome sequences of four mycoparasitic Trichoderma species now forms the basis for large-scale genetic manipulations of these important BCAs. Thus far, only a limited number of dominant selection markers, including Hygromycin B resistance (hph) and the acetamidase-encoding amdS gene, have been available for transformation of Trichoderma spp. For more extensive functional genomics studies the utilization of additional dominant markers will be essential. We established the Escherichia coli neomycin phosphotransferase II-encoding nptII gene as a novel selectable marker for the transformation of Trichoderma atroviride conferring geneticin resistance. The nptII marker cassette was stably integrated into the fungal genome and transformants exhibited unaltered phenotypes compared to the wild-type. Co-transformation of T. atroviride with nptII and a constitutively activated version of the Gα subunit-encoding tga3 gene (tga3Q207L) resulted in a high number of mitotically stable, geneticin-resistant transformants. Further analyses revealed a co-transformation frequency of 68% with 15 transformants having additionally integrated tga3Q207L into their genome. Constitutive activation of the Tga3-mediated signaling pathway resulted in increased vegetative growth and an enhanced ability to antagonize plant pathogenic host fungi. The neomycin phosphotransferase II-encoding nptII gene from Escherichia coli proved to be a valuable tool for conferring geneticin resistance to the filamentous fungus T. atroviride thereby contributing to an enhanced genetic tractability of these important BCAs.
Stemer, Bettina; Melmer, Andreas; Fuchs, Dietmar; Ebenbichler, Christoph; Kemmler, Georg; Deisenhammer, Eberhard A
2015-10-30
Light falling on the retina is converted into an electrical signal which stimulates serotonin synthesis. Previous studies described an increase of plasma and CNS serotonin levels after bright light exposure. Ghrelin and leptin are peptide hormones which are involved in the regulation of hunger/satiety and are related to serotonin. Neopterin and kynurenine are immunological markers which are also linked to serotonin biosynthesis. In this study, 29 healthy male volunteers were exposed to bright (5000lx) and dim (50lx) light conditions for 120min in a cross-over manner. Subjective well-being and hunger as well as various serotonin associated plasma factors were assessed before and after light exposure. Subjective well-being showed a small increase under bright light and a small decrease under dim light, resulting in a significant interaction between light condition and time. Ghrelin concentrations increased significantly under both light conditions, but there was no interaction between light and time. Correspondingly, leptin decreased significantly under both light conditions. Hunger increased significantly with no light-time interaction. We also found a significant decrease of neopterin, tryptophan and tyrosine levels, but no interaction between light and time. In conclusion, ambient light was affecting subjective well-being rather than serotonin associated biological factors. Copyright © 2015. Published by Elsevier Ireland Ltd.
[A Method for Selecting Self-Adoptive Chromaticity of the Projected Markers].
Zhao, Shou-bo; Zhang, Fu-min; Qu, Xing-hua; Zheng, Shi-wei; Chen, Zhe
2015-04-01
The authors designed a self-adaptive projection system which is composed of color camera, projector and PC. In detail, digital micro-mirror device (DMD) as a spatial light modulator for the projector was introduced in the optical path to modulate the illuminant spectrum based on red, green and blue light emitting diodes (LED). However, the color visibility of active markers is affected by the screen which has unknown reflective spectrum as well. Here active markers are projected spot array. And chromaticity feature of markers is sometimes submerged in similar spectral screen. In order to enhance the color visibility of active markers relative to screen, a method for selecting self-adaptive chromaticity of the projected markers in 3D scanning metrology is described. Color camera with 3 channels limits the accuracy of device characterization. For achieving interconversion of device-independent color space and device-dependent color space, high-dimensional linear model of reflective spectrum was built. Prior training samples provide additional constraints to yield high-dimensional linear model with more than three degrees of freedom. Meanwhile, spectral power distribution of ambient light was estimated. Subsequently, markers' chromaticity in CIE color spaces was selected via maximization principle of Euclidean distance. The setting values of RGB were easily estimated via inverse transform. Finally, we implemented a typical experiment to show the performance of the proposed approach. An 24 Munsell Color Checker was used as projective screen. Color difference in the chromaticity coordinates between the active marker and the color patch was utilized to evaluate the color visibility of active markers relative to the screen. The result comparison between self-adaptive projection system and traditional diode-laser light projector was listed and discussed to highlight advantage of our proposed method.
NABIC marker database: A molecular markers information network of agricultural crops.
Kim, Chang-Kug; Seol, Young-Joo; Lee, Dong-Jun; Jeong, In-Seon; Yoon, Ung-Han; Lee, Gang-Seob; Hahn, Jang-Ho; Park, Dong-Suk
2013-01-01
In 2013, National Agricultural Biotechnology Information Center (NABIC) reconstructs a molecular marker database for useful genetic resources. The web-based marker database consists of three major functional categories: map viewer, RSN marker and gene annotation. It provides 7250 marker locations, 3301 RSN marker property, 3280 molecular marker annotation information in agricultural plants. The individual molecular marker provides information such as marker name, expressed sequence tag number, gene definition and general marker information. This updated marker-based database provides useful information through a user-friendly web interface that assisted in tracing any new structures of the chromosomes and gene positional functions using specific molecular markers. The database is available for free at http://nabic.rda.go.kr/gere/rice/molecularMarkers/
Schroecksnadel, Katharina; Winkler, Christiana; Wirleitner, Barbara; Schennach, Harald; Weiss, Günter; Fuchs, Dietmar
2005-01-01
Inflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10-100 muM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses
Orszaghova, Zuzana; Laubertova, Lucia; Sabaka, Peter; Rohdewald, Peter; Durackova, Zdenka; Muchova, Jana
2014-01-01
We examined in vitro antioxidant capacity of polyphenolic extract obtained from the wood of oak Quercus robur (QR), Robuvit, using TEAC (Trolox equivalent antioxidant capacity) method and the effect of its intake on markers of oxidative stress, activity of antioxidant enzymes, and total antioxidant capacity in plasma of 20 healthy volunteers. Markers of oxidative damage to proteins, DNA, and lipids and activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the erythrocytes. We have found an in vitro antioxidant capacity of Robuvit of 6.37 micromole Trolox equivalent/mg of Robuvit. One month intake of Robuvit in daily dose of 300 mg has significantly decreased the serum level of advanced oxidation protein products (AOPP) and lipid peroxides (LP). Significantly increased activities of SOD and CAT as well as total antioxidant capacity of plasma after one month intake of Robuvit have been shown. In conclusion, we have demonstrated for the first time that the intake of Robuvit is associated with decrease of markers of oxidative stress and increase of activity of antioxidant enzymes and total antioxidant capacity of plasma in vivo. PMID:25254080
Chacon-Cabrera, Alba; Mateu-Jimenez, Mercè; Langohr, Klaus; Fermoselle, Clara; García-Arumí, Elena; Andreu, Antoni L; Yelamos, Jose; Barreiro, Esther
2017-12-01
Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1 -/- ) and Parp-2 -/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1 -/- , and Parp-2 -/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1 -/- and Parp-2 -/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention. © 2017 Wiley Periodicals, Inc.
Bosch, Ronald J.; Macatangay, Bernard J.; Rinaldo, Charles R.; Riddler, Sharon A.; Mellors, John W.
2017-01-01
Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but both can persist despite clinically effective ART. The relationships among pre-ART and on-ART levels of HIV-1 and activation are incompletely understood, in part because prior studies have been small or cross-sectional. To address these limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell activation and T cell cycling in a longitudinal cohort of 101 participants who initiated ART and had well-documented sustained suppression of plasma viremia for a median of 7 years. During the first 4 years following ART initiation, HIV-1 DNA declined by 15-fold (93%) whereas cell-associated HIV-1 RNA (CA-RNA) fell 525-fold (>99%). Thereafter, HIV-1 DNA levels continued to decline slowly (5% per year) with a half-life of 13 years. Participants who had higher HIV-1 DNA and CA-RNA before starting treatment had higher levels while on ART, despite suppression of plasma viremia for many years. Markers of inflammation and T cell activation were associated with plasma HIV-1 RNA levels before ART was initiated but there were no consistent associations between these markers and HIV-1 DNA or CA-RNA during long-term ART, suggesting that HIV-1 persistence is not driving or driven by inflammation or activation. Higher levels of inflammation, T cell activation and cycling before ART were associated with higher levels during ART, indicating that immunologic events that occurred well before ART initiation had long-lasting effects despite sustained virologic suppression. These findings should stimulate studies of viral and host factors that affect virologic, inflammatory and immunologic set points prior to ART initiation and should inform the design of strategies to reduce HIV-1 reservoirs and dampen immune activation that persists despite ART. PMID:28426825
Anti-oxidative assays as markers for anti-inflammatory activity of flavonoids.
Chanput, Wasaporn; Krueyos, Narumol; Ritthiruangdej, Pitiporn
2016-11-01
The complexity of in vitro anti-inflammatory assays, the cost and time consumed, and the necessary skills can be a hurdle to apply to promising compounds in a high throughput setting. In this study, several antioxidative assays i.e. DPPH, ABTS, ORAC and xanthine oxidase (XO) were used to examine the antioxidative activity of three sub groups of flavonoids: (i) flavonol: quercetin, myricetin, (ii) flavanone: eriodictyol, naringenin (iii) flavone: luteolin, apigenin. A range of flavonoid concentrations was tested for their antioxidative activities and were found to be dose-dependent. However, the flavonoid concentrations over 50ppm were found to be toxic to the THP-1 monocytes. Therefore, 10, 20 and 50ppm of flavonoid concentrations were tested for their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated THP-1 monocytes. Expression of inflammatory genes, IL-1β, IL-6, IL-8, IL-10 and TNF-α was found to be sequentially decreased when flavonoid concentration increased. Principle component analysis (PCA) was used to investigate the relationship between the data sets of antioxidative assays and the expression of inflammatory genes. The results showed that DPPH, ABTS and ORAC assays have an opposite correlation with the reduction of inflammatory genes. Pearson correlation exhibited a relationship between the ABTS assay and the expression of three out of five analyzed genes; IL-1β, IL-6 and IL-8. Our findings indicate that ABTS assay can potentially be an assay marker for anti-inflammatory activity of flavonoids. Copyright © 2016 Elsevier B.V. All rights reserved.
Niedrig, M; Stolte, N; Fuchs, D; Hunsmann, G; Stahl-Hennig, C
1999-03-05
Investigating new and simple application routes for YF vaccine, four groups of 4-6 rhesus monkeys were vaccinated with live attenuated 17D YF-vaccine. In two groups the vaccine was administered either as spray into the oral cavity, or as an encapsulated form directly into the stomach. Only one out of eight animals developed a humoral immune response against 17D. In the third group receiving the vaccine intranasally by spray and in the fourth group serving as control all ten monkeys developed an immune response. From all except one of these seroconverted monkeys virus could be detected either by virus reisolation or RT-PCR. All these animals showed a serological immune response in immunofluorescence and neutralisation test. Parallel to viremia, an increase of neopterin as an unspecified immune activation marker could be demonstrated for these animals. Intra-nasal application of 17D-vaccine seems to be a good alternative to subcutaneous immunisation in mass vaccination campaigns.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Adams, M.R.
This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.
Ludwig, Kirsten; Kornblum, Harley I
2017-09-01
Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.
Patrizi, Alfredo; Pennestrì, Ettore; Valentini, Pier Paolo
2016-01-01
The paper deals with the comparison between a high-end marker-based acquisition system and a low-cost marker-less methodology for the assessment of the human posture during working tasks. The low-cost methodology is based on the use of a single Microsoft Kinect V1 device. The high-end acquisition system is the BTS SMART that requires the use of reflective markers to be placed on the subject's body. Three practical working activities involving object lifting and displacement have been investigated. The operational risk has been evaluated according to the lifting equation proposed by the American National Institute for Occupational Safety and Health. The results of the study show that the risk multipliers computed from the two acquisition methodologies are very close for all the analysed activities. In agreement to this outcome, the marker-less methodology based on the Microsoft Kinect V1 device seems very promising to promote the dissemination of computer-aided assessment of ergonomics while maintaining good accuracy and affordable costs. PRACTITIONER’S SUMMARY: The study is motivated by the increasing interest for on-site working ergonomics assessment. We compared a low-cost marker-less methodology with a high-end marker-based system. We tested them on three different working tasks, assessing the working risk of lifting loads. The two methodologies showed comparable precision in all the investigations.
Serum markers of bone metabolism show bone loss in hibernating bears
Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.
2003-01-01
Disuse osteopenia was studied in hibernating black bears (Ursus americanus) using serum markers of bone metabolism. Blood samples were collected from male and female, wild black bears during winter denning and active summer periods. Radioimmunoassays were done to determine serum concentrations of cortisol, the carboxy-terminal cross-linked telopeptide, and the carboxy-terminal propeptide of Type I procollagen, which are markers of hone resorption and formation, respectively. The bone resorption marker was significantly higher during winter hibernation than it was in the active summer months, but the bone formation marker was unchanged, suggesting an imbalance in bone remodeling and a net bone loss during disuse. Serum cortisol was significantly correlated with the bone resorption marker, but not with the bone formation marker. The bone formation marker was four- to fivefold higher in an adolescent and a 17-year-old bear early in the remobilization period compared with the later summer months. These findings raise the possibility that hibernating black bears may minimize bone loss during disuse by maintaining osteoblastic function and have a more efficient compensatory mechanism for recovering immobilization-induced bone loss than that of humans or other animals.
Salivary exoglycosidases as markers of alcohol dependence.
Waszkiewicz, Napoleon; Chojnowska, Sylwia; Zalewska, Anna; Zwierz, Krzysztof; Szulc, Agata; Szajda, Sławomir Dariusz
2014-01-01
Some salivary markers of alcohol abuse/dependence have been proposed so far: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide, ethyl sulfate, sialic acid, β-hexosaminidase A, oral peroxidase, methanol, diethylene/ethylene glycol, α-amylase, clusterin, haptoglobin, heavy/light chains of immunoglobulins and transferrin. To investigate the effect of chronic alcohol drinking and smoking on the activity (pKat/ml) and output (pKat/min) of salivary lysosomal exoglycosidases: α-fucosidase (FUC), α-mannosidase (MAN), β-galactosidase (GAL), and β-glucuronidase (GLU), and their applicability as markers of alcohol dependence. The activity of FUC, MAN, GAL and GLU was measured colorimetrically in the saliva of healthy social drinkers, alcohol-dependent non-smokers and alcohol-dependent smokers. We observed an increased salivary activity of FUC, GAL, GLU and MAN, as well as an increased output of GAL and GLU, in comparison with controls. The highest increase in the activity/output was found in salivary GLU and MAN (GLU, even 7- to 18-fold), and the least in GAL. We found an excellent sensitivity and specificity and a high accuracy (measured by the area under the ROC curve) for salivary FUC, GLU and MAN activities. The salivary GLU activity positively correlated with the number of days of last alcohol intoxication. Salivary activity of FUC, GAL and MAN, but not GLU, positively correlated with the periodontal parameters such as gingival index and papilla bleeding index. Although we found an excellent sensitivity and specificity as well as a high accuracy for the salivary activity of FUC, GLU and MAN, the GLU activity seems to be mostly applicable as a marker of chronic alcohol drinking (alcohol dependence). © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.
Pochigaeva, Ksenia; Druzhkova, Tatiana; Yakovlev, Alexander; Onufriev, Mikhail; Grishkina, Maria; Chepelev, Aleksey; Guekht, Alla; Gulyaeva, Natalia
2017-04-01
Hair cortisol is regarded as a promising marker of hypothalamic-pituitary-adrenal axis (HPAA) activity alterations due to stress, somatic and mental health conditions. Hair cortisol was previously reported to be elevated in patients with depression, however the data related to remission and recurrent depressive episodes are different. In this study, levels of hair cortisol were assessed in female patients with major depressive disorder (MDD) and the validity of hair cortisol as a marker of HPAA activity in this condition was evaluated. Hair cortisol was measured in 1 cm hair segments of 21 female patients with MDD and 22 female age-matched controls using enzyme-immunoassay analysis. Concurrently, serum cortisol was assessed and psychological status was evaluated using 17-item Hamilton Depression Rating Scale (HAMD-17), Beck Depression Inventory (BDI) and the Spielberger state trait anxiety inventory (STAI). The levels of hair cortisol were significantly lower in the MDD group, while serum cortisol levels were significantly higher in patients, as compared with controls. A significant negative correlation was found between HAMD-17 scores and hair cortisol. Decreased hair cortisol found in female patients with MDD as compared to controls suggests downregulation of HPAA activity during the preceding month. Further studies are needed to investigate the profiles of hair cortisol at different stages of depressive disorder to establish this parameter as a handy clinical tool.
Keighren, Margaret A; Flockhart, Jean; Hodson, Benjamin A; Shen, Guan-Yi; Birtley, James R; Notarnicola-Harwood, Antonio; West, John D
2015-08-01
Recent reports of a new generation of ubiquitous transgenic chimaera markers prompted us to consider the criteria used to evaluate new chimaera markers and develop more objective assessment methods. To investigate this experimentally we used several series of fetal and adult chimaeras, carrying an older, multi-copy transgenic marker. We used two additional independent markers and objective, quantitative criteria for cell selection and cell mixing to investigate quantitative and spatial aspects of developmental neutrality. We also suggest how the quantitative analysis we used could be simplified for future use with other markers. As a result, we recommend a five-step procedure for investigators to evaluate new chimaera markers based partly on criteria proposed previously but with a greater emphasis on examining the developmental neutrality of prospective new markers. These five steps comprise (1) review of published information, (2) evaluation of marker detection, (3) genetic crosses to check for effects on viability and growth, (4) comparisons of chimaeras with and without the marker and (5) analysis of chimaeras with both cell populations labelled. Finally, we review a number of different chimaera markers and evaluate them using the extended set of criteria. These comparisons indicate that, although the new generation of ubiquitous fluorescent markers are the best of those currently available and fulfil most of the criteria required of a chimaera marker, further work is required to determine whether they are developmentally neutral.
TiO2 nanoparticles and bulk material stimulate human peripheral blood mononuclear cells☆
Becker, Kathrin; Schroecksnadel, Sebastian; Geisler, Simon; Carriere, Marie; Gostner, Johanna M.; Schennach, Harald; Herlin, Nathalie; Fuchs, Dietmar
2014-01-01
Nanomaterials are increasingly produced and used throughout recent years. Consequently the probability of exposure to nanoparticles has risen. Because of their small 1–100 nm size, the physicochemical properties of nanomaterials may differ from standard bulk materials and may pose a threat to human health. Only little is known about the effects of nanoparticles on the human immune system. In this study, we investigated the effects of TiO2 nanoparticles and bulk material in the in vitro model of human peripheral blood mononuclear cells (PBMC) and cytokine-induced neopterin formation and tryptophan breakdown was monitored. Both biochemical processes are closely related to the course of diseases like infections, atherogenesis and neurodegeneration. OCTi60 (25 nm diameter) TiO2 nanoparticles and bulk material increased neopterin production in unstimulated PBMC and stimulated cells significantly, the effects were stronger for OCTi60 compared to bulk material, while P25 TiO2 (25 nm diameter) nanoparticles had only little influence. No effect of TiO2 nanoparticles on tryptophan breakdown was detected in unstimulated cells, whereas in stimulated cells, IDO activity and IFN-γ production were suppressed but only at the highest concentrations tested. Because neopterin was stimulated and tryptophan breakdown was suppressed in parallel, data suggests that the total effect of particles would be strongly pro-inflammatory. PMID:24361406
PANDAS and anorexia nervosa--a spotters' guide: suggestions for medical assessment.
Vincenzi, Brenda; O'Toole, Julie; Lask, Bryan
2010-03-01
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) should be considered in sudden onset, prepubertal Anorexia Nervosa (AN), arising shortly after an apparent streptococcal infection. However, the absence of a specific biological marker of PANDAS renders the diagnosis difficult. This paper critically reviews available tests for PANDAS and recommends a standardized approach to its investigation. Medline database review between 1990 and 2008. Existing tests may be categorized as: (i) Non-specific markers of inflammation or immune response (Erythrocyte sedimentation rate, ESR; C-reactive protein, CRP; Neopterin), (ii) specific markers of streptococcal infection (throat swab and anti-streptococcal antibodies, Anti-streptolysin, ASO; Antideoxyribonuclease B, antiDNaseB), (iii) non-specific markers of auto-immune reaction (Antineuronal antibodies, AnAb; D8/17). No one test reliably identifies PANDAS. The lack of specificity and methodological problems may lead to errors of diagnosis. When PANDAS-Anorexia Nervosa (PANDAS-AN) is suspected clinically we recommend conducting all the above investigations. The more positive results there are the more likely is the diagnosis, but particular weighting should be given to AnAb and D8/17. Copyright (c) 2010 John Wiley & Sons, Ltd., and Eating Disorders Association.
Martins, Clarice; Aires, Luisa; Júnior, Ismael Freitas; Silva, Gustavo; Silva, Alexandre; Lemos, Luís; Mota, Jorge
2015-01-01
Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent complications associated with excess adiposity and has been identified as the leading cause of liver disease in pediatric populations worldwide. Because cardiorespiratory fitness (CRF) is related to physical activity (PA) levels, and increased PA plays a protective role against NAFLD risk factors, the aim of this study was to analyze the association between PA and a fatty liver marker (alanine aminotransferase - ALT) in obese children and adolescents, independently of central adiposity or CRF. 131 obese children (83 girls, 7-15 year-olds) involved in a PA promotion program comprised the sample. Measurements included anthropometric and body composition evaluations (DEXA), biological measurements (venipuncture), CRF (progressive treadmill test), PA (accelerometry), and maturational stage (Tanner criteria). The associations between ALT with PA intensities, central obesity, and CRF were calculated by three different models of linear regression, adjusted for potential confounders. Level of significance was set at 95%. RESULTS: ALT was negatively associated with MVPA (β = -0.305), and CRF (β = -0.426), and positively associated with central obesity (β=.468). After adjustment for central obesity the negative and statistically significant association between ALT with MVPA (β = -0.364) and CRF (β = -0.550) still persists while a positive and significantly correlation was shown between ALT and SB (β = 0.382). Additional adjustment for CRF (Model 3) showed significant associations for all the PA intensities analyzed including light activity. PA at different intensities is associated to a fatty liver marker in obese children and adolescents, independently of central adiposity or CRF. Key points In a previous study our group observed that there might be a potential protective effect of cardiorespiratory fitness (CRF) against abnormal ALT values; Considering that CRF is related to physical activity (PA
Accuracy of an optical active-marker system to track the relative motion of rigid bodies.
Maletsky, Lorin P; Sun, Junyi; Morton, Nicholas A
2007-01-01
The measurement of relative motion between two moving bones is commonly accomplished for in vitro studies by attaching to each bone a series of either passive or active markers in a fixed orientation to create a rigid body (RB). This work determined the accuracy of motion between two RBs using an Optotrak optical motion capture system with active infrared LEDs. The stationary noise in the system was quantified by recording the apparent change in position with the RBs stationary and found to be 0.04 degrees and 0.03 mm. Incremental 10 degrees rotations and 10-mm translations were made using a more precise tool than the Optotrak. Increasing camera distance decreased the precision or increased the range of values observed for a set motion and increased the error in rotation or bias between the measured and actual rotation. The relative positions of the RBs with respect to the camera-viewing plane had a minimal effect on the kinematics and, therefore, for a given distance in the volume less than or close to the precalibrated camera distance, any motion was similarly reliable. For a typical operating set-up, a 10 degrees rotation showed a bias of 0.05 degrees and a 95% repeatability limit of 0.67 degrees. A 10-mm translation showed a bias of 0.03 mm and a 95% repeatability limit of 0.29 mm. To achieve a high level of accuracy it is important to keep the distance between the cameras and the markers near the distance the cameras are focused to during calibration.
Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S
2016-12-01
We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.
Hoel, Hedda; Hove-Skovsgaard, Malene; Hov, Johannes R; Gaardbo, Julie Christine; Holm, Kristian; Kummen, Martin; Rudi, Knut; Nwosu, Felix; Valeur, Jørgen; Gelpi, Marco; Seljeflot, Ingebjørg; Ueland, Per Magne; Gerstoft, Jan; Ullum, Henrik; Aukrust, Pål; Nielsen, Susanne Dam; Trøseid, Marius
2018-04-30
HIV infection and type 2 diabetes are associated with altered gut microbiota, chronic inflammation, and increased cardiovascular risk. We aimed to investigate the combined effect of these diseases on gut microbiota composition and related metabolites, and a potential relation to endothelial dysfunction in individuals with HIV-infection only (n = 23), diabetes only (n = 16) or both conditions (n = 21), as well as controls (n = 24). Fecal microbiota was analyzed by Illumina sequencing of the 16 S rRNA gene. Markers of endothelial dysfunction (asymmetric dimethylarginine [ADMA]), tryptophan catabolism (kynurenine/tryptophan [KT]-ratio), and inflammation (neopterin) were measured by liquid chromatography-tandem mass spectrometry. The combination of HIV and type 2 diabetes was associated with reduced gut microbiota diversity, increased plasma KT-ratio and neopterin. Microbial genes related to tryptophan metabolism correlated with KT-ratio and low alpha diversity, in particular in HIV-infected with T2D. In multivariate analyses, KT-ratio associated with ADMA (β = 4.58 [95% CI 2.53-6.63], p < 0.001), whereas microbiota composition per se was not associated with endothelial dysfunction. Our results indicate that tryptophan catabolism may be related to endothelial dysfunction, with a potentially detrimental interaction between HIV and diabetes. The potential contribution of gut microbiota and the impact for cardiovascular risk should be further explored in prospective studies powered for clinical end points.
Smart magnetic markers use in hydraulic fracturing.
Zawadzki, Jarosław; Bogacki, Jan
2016-11-01
One of the main challenges and unknowns during shale gas exploration is to assess the range and efficiency of hydraulic fracturing. It is also essential to assess the distribution of proppant, which keeps the fracture pathways open. Solving these problems may considerably increase the efficiency of the shale gas extraction. Because of that, the idea of smart magnetic marker, which can be detected when added to fracturing fluid, has been considered for a long time. This study provides overview of the possibilities of magnetic marker application for shale gas extraction. The imaging methods using electromagnetic markers, are considered or developed in two directions. The first possibility is the markers' electromagnetic activity throughout the whole volume of the fracturing fluid. Thus, it can be assumed that the whole fracturing fluid is the marker. Among these type of hydraulic fracturing solutions, ferrofluid could be considered. The second possibility is marker, which is just one of many components of the fracturing fluid. In this case feedstock magnetic materials, ferrites and nanomaterials could be considered. Magnetic properties of magnetite could be too low and ferrofluids' or nanomaterials' price is unacceptably high. Because of that, ferrites, especially ZnMn ferrites seems to be the best material for magnetic marker. Because of the numerous applications in electronics, it is cheap and easily available, although the price is higher, then that of magnetite. The disadvantage of using ferrite, could be too small mechanical strength. It creates an essential need for combining magnetic marker with proppant into magnetic-ceramic composite. Copyright © 2016 Elsevier Ltd. All rights reserved.
Gundle, Kenneth R.; White, Jedediah K.; Conrad, Ernest U.; Ching, Randal P.
2017-01-01
Introduction: Surgical navigation systems are increasingly used to aid resection and reconstruction of osseous malignancies. In the process of implementing image-based surgical navigation systems, there are numerous opportunities for error that may impact surgical outcome. This study aimed to examine modifiable sources of error in an idealized scenario, when using a bidirectional infrared surgical navigation system. Materials and Methods: Accuracy and precision were assessed using a computerized-numerical-controlled (CNC) machined grid with known distances between indentations while varying: 1) the distance from the grid to the navigation camera (range 150 to 247cm), 2) the distance from the grid to the patient tracker device (range 20 to 40cm), and 3) whether the minimum or maximum number of bidirectional infrared markers were actively functioning. For each scenario, distances between grid points were measured at 10-mm increments between 10 and 120mm, with twelve measurements made at each distance. The accuracy outcome was the root mean square (RMS) error between the navigation system distance and the actual grid distance. To assess precision, four indentations were recorded six times for each scenario while also varying the angle of the navigation system pointer. The outcome for precision testing was the standard deviation of the distance between each measured point to the mean three-dimensional coordinate of the six points for each cluster. Results: Univariate and multiple linear regression revealed that as the distance from the navigation camera to the grid increased, the RMS error increased (p<0.001). The RMS error also increased when not all infrared markers were actively tracking (p=0.03), and as the measured distance increased (p<0.001). In a multivariate model, these factors accounted for 58% of the overall variance in the RMS error. Standard deviations in repeated measures also increased when not all infrared markers were active (p<0.001), and as the
Gundle, Kenneth R; White, Jedediah K; Conrad, Ernest U; Ching, Randal P
2017-01-01
Surgical navigation systems are increasingly used to aid resection and reconstruction of osseous malignancies. In the process of implementing image-based surgical navigation systems, there are numerous opportunities for error that may impact surgical outcome. This study aimed to examine modifiable sources of error in an idealized scenario, when using a bidirectional infrared surgical navigation system. Accuracy and precision were assessed using a computerized-numerical-controlled (CNC) machined grid with known distances between indentations while varying: 1) the distance from the grid to the navigation camera (range 150 to 247cm), 2) the distance from the grid to the patient tracker device (range 20 to 40cm), and 3) whether the minimum or maximum number of bidirectional infrared markers were actively functioning. For each scenario, distances between grid points were measured at 10-mm increments between 10 and 120mm, with twelve measurements made at each distance. The accuracy outcome was the root mean square (RMS) error between the navigation system distance and the actual grid distance. To assess precision, four indentations were recorded six times for each scenario while also varying the angle of the navigation system pointer. The outcome for precision testing was the standard deviation of the distance between each measured point to the mean three-dimensional coordinate of the six points for each cluster. Univariate and multiple linear regression revealed that as the distance from the navigation camera to the grid increased, the RMS error increased (p<0.001). The RMS error also increased when not all infrared markers were actively tracking (p=0.03), and as the measured distance increased (p<0.001). In a multivariate model, these factors accounted for 58% of the overall variance in the RMS error. Standard deviations in repeated measures also increased when not all infrared markers were active (p<0.001), and as the distance between navigation camera and physical
Arko-Mensah, J; Rahman, M J; Julián, E; Horner, G; Singh, M; Fernández, C
2009-08-01
Immunological tests for the diagnosis of tuberculosis (TB) have relied mostly on detection of immune markers in serum or release of cytokines by mononuclear cells in vitro. These tests, although useful, sometimes fail to discriminate between active infection and contact with mycobacteria or vaccination. TB is primarily a disease of the lung, and therefore identification of immunological markers in the respiratory tract will be more likely to reflect the infection status or disease activity. In this study, it is demonstrated that active infection of mice with Mycobacterium bovis bacille Calmette-Guérin (BCG), but not exposure to heat-killed BCG, induced production of interleukin-12 (IL-12), interferon-gamma (IFN-gamma) or soluble tumour necrosis factor receptors (sTNFRs) locally in the lungs, as detected in bronchoalveolar lavage (BAL) fluid. There was a strong correlation between bacterial growth in the lung and levels of sTNFRs, and to some extent IL-12 and IFN-gamma, in BAL fluid. Furthermore, sTNFR levels increased significantly in BAL fluid after reactivation of controlled infection with dexamethasone, and this correlated with increased bacterial growth in the lungs. Finally, infection, but not exposure to non-replicating mycobacteria, induced specific IgG and IgA in BAL fluid. Elevated levels of all biomarkers measured were also detected in the serum, but correlation with infection was not as clear as in the case of BAL fluid. Taken together, the detection of sTNFRs and mycobacterium-specific antibodies, especially IgA, locally in the lungs could be used as immunological markers for the diagnosis of TB.
NASA Astrophysics Data System (ADS)
Daye, Dania; Bobo, Ezra; Baumann, Bethany; Ioannou, Antonios; Conant, Emily F.; Maidment, Andrew D. A.; Kontos, Despina
2011-03-01
Mammographic parenchymal texture patterns have been shown to be related to breast cancer risk. Yet, little is known about the biological basis underlying this association. Here, we investigate the potential of mammographic parenchymal texture patterns as an inherent phenotypic imaging marker of endogenous hormonal exposure of the breast tissue. Digital mammographic (DM) images in the cranio-caudal (CC) view of the unaffected breast from 138 women diagnosed with unilateral breast cancer were retrospectively analyzed. Menopause status was used as a surrogate marker of endogenous hormonal activity. Retroareolar 2.5cm2 ROIs were segmented from the post-processed DM images using an automated algorithm. Parenchymal texture features of skewness, coarseness, contrast, energy, homogeneity, grey-level spatial correlation, and fractal dimension were computed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate feature classification performance in distinguishing between 72 pre- and 66 post-menopausal women. Logistic regression was performed to assess the independent effect of each texture feature in predicting menopause status. ROC analysis showed that texture features have inherent capacity to distinguish between pre- and post-menopausal statuses (AUC>0.5, p<0.05). Logistic regression including all texture features yielded an ROC curve with an AUC of 0.76. Addition of age at menarche, ethnicity, contraception use and hormonal replacement therapy (HRT) use lead to a modest model improvement (AUC=0.78) while texture features maintained significant contribution (p<0.05). The observed differences in parenchymal texture features between pre- and post- menopausal women suggest that mammographic texture can potentially serve as a surrogate imaging marker of endogenous hormonal activity.
Kırmızıbekmez, Hasan; İnan, Yiğit; Reis, Rengin; Sipahi, Hande; Gören, Ahmet C; Yeşilada, Erdem
2018-03-12
Phytochemical investigations on the EtOH extract of Clematis viticella led to the isolation of six flavonoid glycosides, isoorientin (1), isoorientin 3'-O-methyl ether (2), quercetin 7-O-α-L-rhamnopyranoside (3), quercetin 3,7-di-O-α-L-rhamnopyranoside (4), manghaslin (5) and chrysoeriol 7-O-β-D-glucopyranoside (6), one phenylethanol derivative, hydroxytyrosol (7), along with three phenolic acids, caffeic acid (8), (E)-p-coumaric acid (9) and p-hydroxybenzoic acid (10). The structures of the isolates were elucidated on the basis of NMR and HR-MS data. All compounds were isolated from C. viticella for the first time. Compounds 7 and 8 showed significant anti-inflammatory activity at 100 μM by reducing the release of NO in LPS-stimulated macrophages comparable to positive control indomethacin. Compounds 3 and 7 exhibited anti-inflammatory activity through lowering the levels of TNF-α while 1, 3 and 5 decreased the levels of neopterin better than the positive controls.
Syed, Salma S; Balluz, Rula S; Kabagambe, Edmond K; Meyer, William A; Lukas, Susan; Wilson, Craig M; Kapogiannis, Bill G; Nachman, Sharon A; Sleasman, John W
2013-03-01
Cardiovascular disease (CVD) biomarkers were examined in a cohort of HIV-infected and HIV-uninfected adolescents who participated in Adolescent Trials Network study 083 utilizing samples from the Reaching for Excellence in Adolescent Care cohort, a longitudinal study of youth infected through adult risk behavior. Nonfasting blood samples from 97 HIV-infected and 81 HIV-uninfected adolescents infected by adult risk behaviors were analyzed for total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), triglycerides, apolipoprotein A-I, high-sensitivity C-reactive protein (hsCRP), soluble vascular adhesion molecule-1 (sVCAM-1), myeloperoxidase, and neopterin at baseline and 18 months later. Results were analyzed using ANOVA, Wilcoxon signed-rank, and paired t tests. Among infected subjects 67 received antiretroviral therapy and 30 were treatment naive. The HIV-infected and HIV-uninfected subjects were similar in gender, ethnicity, and cardiovascular risk factors such as smoking and obesity. In all groups lipid parameters were within accepted guidelines for cardiovascular risk. Among HIV-infected youth on antiretroviral therapy (ART), HDL and apoprotein A-I were significantly lower when compared to uninfected youth. hsCRP was not elevated and thus not predictive for risk in any group. sVCAM-1 levels were significantly elevated in both HIV-infected groups: 1,435 ng/ml and 1,492 ng/ml in untreated and treated subjects, respectively, and 1,064 ng/ml in the uninfected group (p<0.0001). Across all groups neopterin correlated with sVCAM at 18 months (Spearman correlation coefficient 0.58, p<0.0001). Only 9% of ART-treated subjects fully suppressed virus. Lipid profiles and hsCRP, traditional markers of cardiovascular disease, are not abnormal among HIV-infected youth but elevated sVCAM may be an early marker of atherosclerosis.
Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection.
Ahlgren, Erika; Hagberg, Lars; Fuchs, Dietmar; Andersson, Lars-Magnus; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus
2016-01-01
To investigate the role of homocysteine in neuronal injury in HIV infection. Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
Lustenberger, Caroline; Mouthon, Anne-Laure; Tesler, Noemi; Kurth, Salome; Ringli, Maya; Buchmann, Andreas; Jenni, Oskar G; Huber, Reto
2017-01-01
Reliable markers for brain maturation are important to identify neural deviations that eventually predict the development of mental illnesses. Recent studies have proposed topographical EEG-derived slow wave activity (SWA) during NREM sleep as a mirror of cortical development. However, studies about the longitudinal stability as well as the relationship with behavioral skills are needed before SWA topography may be considered such a reliable marker. We examined six subjects longitudinally (over 5.1 years) using high-density EEG and a visuomotor learning task. All subjects showed a steady increase of SWA at a frontal electrode and a decrease in central electrodes. Despite these large changes in EEG power, SWA topography was relatively stable within each subject during development indicating individual trait-like characteristics. Moreover, the SWA changes in the central cluster were related to the development of specific visuomotor skills. Taken together with the previous work in this domain, our results suggest that EEG sleep SWA represents a marker for motor skill development and further supports the idea that SWA mirrors cortical development during childhood and adolescence. © 2016 Wiley Periodicals, Inc.
Hori, Koji; Konishi, Kimiko; Hachisu, Mitsugu
2011-06-01
We reviewed the importance of measuring serum anticholinergic activity (SAA) in patients with Alzheimer's disease (AD). Since Tune and Coyle reported a simple method for assessing SAA using radioreceptor-binding assay, SAA is assumed to be the cumulative activity of parent medications and their metabolites and its relationship with delirium and cognitive functions has been debated. However, we evaluated the SAA in AD patients and SAA was correlated with prescription of antipsychotic medications, cognitive dysfunctions, severity of AD and psychotic symptoms, especially, with delusion and diurnal rhythm disturbance. From these results, we should not only pay attention to avoiding the prescription of medications with anticholinergic activity but also we speculated that AA appeared endogenously in AD and accelerated AD pathology. Moreover, there might be the possibility that SAA has predictive value for assessing the progressiveness of AD and as a biological marker for AD.
Lepri, O.; Bassie, L.; Thu-Hang, P.; Christou, P.; Capell, T.
2002-09-01
We used the polyamine biosynthetic pathway and rice as a relevant model to understand the genetic basis of variation in endogenous levels of metabolites and key enzymes involved in the pathway. Wild-type tissues and also tissues containing a commonly used selectable marker gene were employed. We detected a wide variation in levels of arginine decarboxylase activity and in the three polyamines, putrescine, spermidine and spermine, in different tissues and varieties, but this was not dependent on the presence of the selectable marker. A more-extensive profile of enzyme activities (ADC, ODC, SAMDC, DAO and PAO) and polyamine levels in different tissues was generated in two different varieties. Our results indicate that genetic background is important in terms of the basal levels of metabolites and enzyme activity, particularly in situations in which we aim to engineer metabolic pathways that are also encoded by homologous endogenous genes. We did not find any evidence that the presence of a selectable marker in any way influences enzyme activity or metabolite levels.
ERIC Educational Resources Information Center
Healthy Schools Network, Inc., 2011
2011-01-01
Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…
Fraile-Bermúdez, A B; Kortajarena, M; Zarrazquin, I; Maquibar, A; Yanguas, J J; Sánchez-Fernández, C E; Gil, J; Irazusta, A; Ruiz-Litago, F
2015-10-01
The aim of the present study was to examine the relationship between objective data of physical activity and markers of oxidative stress in older men and women. Participants were old adults, aged≥60years (61 women and 34 men) who were all capable of performing basic daily activities by themselves and lived on their own. To describe physical activity we used objective data measured by accelerometers which record active and sedentary periods during everyday life for five days. Determination of oxidative stress was conducted from three perspectives: determination plasma total antioxidant status (TAS), plasma antioxidant enzyme activities, i.e., glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD), and membrane lipid peroxidation (TBARS). In the group of women, those who met physical activity recommendations (WR) had lower level of TAS. In addition, the moderate to vigorous physical activity (MVPA) was negatively correlated with TAS. Simultaneously, MVPA was correlated with increase in the GPx antioxidant enzyme activity, and the counts per minute were positively correlated with CAT activity. In the group of men, the cpm and the MVPA were negatively correlated with lipid peroxidation while lifestyle physical activity was positively correlated with CAT activity. These findings suggest that MVPA in the elderly although it is related to a decrease in the TAS in women, induces adaptive increase in antioxidant enzyme activity and decreases lipid peroxidation in both women and men. These results suggest that at this time of life, it is not only the amount of physical activity performed that is important but also its intensity. Copyright © 2015 Elsevier Inc. All rights reserved.
Vijayamahantesh; Amit, Ajay; Dikhit, Manas R.; Pandey, Raj K.; Singh, Kuljit; Mishra, Ritesh; Das, V. N. R; Das, Pradeep; Bimal, Sanjiva
2016-01-01
Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL. PMID:27186641
Vijayamahantesh; Amit, Ajay; Dikhit, Manas R; Pandey, Raj K; Singh, Kuljit; Mishra, Ritesh; Das, V N R; Das, Pradeep; Bimal, Sanjiva
2016-01-01
Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL.
Markus, Hugh S; Hunt, Beverley; Palmer, Kiran; Enzinger, Christian; Schmidt, Helena; Schmidt, Reinhold
2005-07-01
The pathogenesis of cerebral small vessel disease (SVD) is poorly understood, but endothelial activation and dysfunction may play a causal role. Cross-sectional studies have found increased circulating markers of endothelial activation, but this study design cannot exclude causality from secondary elevations. Confluent white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) appear to represent asymptomatic cerebral SVD. In a prospective study, we determined whether circulating markers of endothelial activation predicted progression of WMH. In the community-based Austrian Stroke Prevention Study, MRI was performed at baseline in 296 subjects and repeated at 3 and 6 years. The following were measured on baseline plasma samples: intercellular adhesion molecule (ICAM), thrombomodulin, tissue factor plasma inhibitor, prothrombin fragments 1 and 2, and D-dimers. ICAM was associated with age- and gender-adjusted WMH lesion progression at both 3 and 6 years, respectively; (odds ratio [OR], 1.007; 95% confidence interval [CI], 1.002 to 1.012; P=0.004; and OR, 1.004; 95% CI, 1.000 to 1.009 per ng/mL; P=0.057). After multivariate analysis controlling for other cardiovascular risk factors and C-reactive protein, 3-year OR was 1.010 (95% CI, 1.004 to 1.017; P=0.001) and 6-year OR was 1.008 (1.002 to 1.014 per ng/mL; P=0.006). Baseline log lesion volume was a strong independent predictor of progression but associations remained after controlling for this (3-year OR, 1.011; 95% CI, 1.002 to 1.020; P=0.013; and 6-year OR, 1.009; 95% CI, 1.000 to 1.017; P=0.039 per ng/mL). There was no association between WMH progression and other markers. ICAM levels are related to progression of WMH on MRI. The prospective study design increases the likelihood that this association is causal and supports a role of endothelial cell activation in disease pathogenesis. In contrast, we found no evidence for coagulation activation being important.
Fonseca, João Eurico; Cavaleiro, João; Teles, José; Sousa, Elsa; Andreozzi, Valeska L; Antunes, Marília; Amaral-Turkman, Maria A; Canhão, Helena; Mourão, Ana F; Lopes, Joana; Caetano-Lopes, Joana; Weinmann, Pamela; Sobral, Marta; Nero, Patrícia; Saavedra, Maria J; Malcata, Armando; Cruz, Margarida; Melo, Rui; Braña, Araceli; Miranda, Luis; Patto, José V; Barcelos, Anabela; da Silva, José Canas; Santos, Luís M; Figueiredo, Guilherme; Rodrigues, Mário; Jesus, Herberto; Quintal, Alberto; Carvalho, Teresa; da Silva, José A Pereira; Branco, Jaime; Queiroz, Mário Viana
2007-01-01
The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.
Fonseca, João Eurico; Cavaleiro, João; Teles, José; Sousa, Elsa; Andreozzi, Valeska L; Antunes, Marília; Amaral-Turkman, Maria A; Canhão, Helena; Mourão, Ana F; Lopes, Joana; Caetano-Lopes, Joana; Weinmann, Pamela; Sobral, Marta; Nero, Patrícia; Saavedra, Maria J; Malcata, Armando; Cruz, Margarida; Melo, Rui; Braña, Araceli; Miranda, Luis; Patto, José V; Barcelos, Anabela; da Silva, José Canas; Santos, Luís M; Figueiredo, Guilherme; Rodrigues, Mário; Jesus, Herberto; Quintal, Alberto; Carvalho, Teresa; da Silva, José A Pereira; Branco, Jaime; Queiroz, Mário Viana
2007-01-01
The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-α) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-α gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-α promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD. PMID:17408492
NASA Astrophysics Data System (ADS)
Mahadewi, Alfiani Guntari; Christina, Daisy; Hermansyah, Heri; Wijanarko, Anondho; Farida, Siti; Adawiyah, Robiatul; Rohmatin, Etin; Sahlan, Muhamad
2018-02-01
The increase in fungal resistance against antifungal drugs available in the market will reduce the effectiveness of treatment for Candidiasis. Propolis contains various compounds with antifungal properties Candida albicans, but the content of each type is very diverse. The sample used was Sulawesi propolis type smooth (taken from inside the nest), rough (taken from outside the hive) and mix (a combination of both). Anti-C. albicans molecule marker is a marker compound for selecting propolis with the ability to overcome Candidiasis. The initial step was to test the levels of flavonoids and phenolic by using UV-Vis spectrometry method. It was founded that each sample was not always superior to any substance, so propolis cannot be directly selected. In Phenolic content, mix propolis has the highest value than other 5.109%. In Flavonoid content, propolis smooth has the highest value than other, 16.38%. Furthermore, propolis selected by antifungal activity test with good diffusion method at the concentration propolis 5% either 7%, the inhibitory diameter zone propolis smooth and rough has same value 10 mm. Propolis mix has an advantage while propolis smooth and rough have the same capability range 12 mm and 13 mm. In this study, the phenolic content plays a major role in antifungal cases.
Cury, Didia Bismara; Mizsputen, Sender Jankiel; Versolato, Clara; Miiji, Luciana Odashiro; Pereira, Edson; Delboni, Maria Aparecida; Schor, Nestor; Moss, Alan C.
2014-01-01
Background and aim Serum calprotectin is elevated in patients with inflammatory bowel disease (IBD). Whether it correlates other markers of disease activity is unknown. The aim of this study was to correlate serum calprotectin with biochemical and histological measures of intestinal inflammation. Materials and methods TNBS colitis was induced in wistar rats, and serial blood samples were collected at 0, 3, and 12 days. Animals were subsequently sacrificed for pathological evaluation at day 12. Serum calprotectin and cytokines were measured by ELISA. Pathologic changes were classified at the macroscopic and microscopic levels. Results TNBS colitis induced elevated serum calprotectin, TNF and IL-6 within 24 h. Levels of serum calprotectin remained elevated in parallel to persistence of loose stool and weight loss to day 12. Serum calprotectin levels correlated with serum levels of TNF-α and IL6 (p < 0.001), but not CRP. Animals with liquid stool had significantly higher levels of serum calprotectin than control animals. There was a correlation between macroscopic colitis scores, and levels of serum calprotectin. Conclusion Serum calprotectin levels correlate with biochemical and histological markers of inflammation in TNBS colitis. This biomarker may have potential for diagnostic use in patients with IBD. PMID:23685388
Evaluating surrogate endpoints, prognostic markers, and predictive markers: Some simple themes.
Baker, Stuart G; Kramer, Barnett S
2015-08-01
A surrogate endpoint is an endpoint observed earlier than the true endpoint (a health outcome) that is used to draw conclusions about the effect of treatment on the unobserved true endpoint. A prognostic marker is a marker for predicting the risk of an event given a control treatment; it informs treatment decisions when there is information on anticipated benefits and harms of a new treatment applied to persons at high risk. A predictive marker is a marker for predicting the effect of treatment on outcome in a subgroup of patients or study participants; it provides more rigorous information for treatment selection than a prognostic marker when it is based on estimated treatment effects in a randomized trial. We organized our discussion around a different theme for each topic. "Fundamentally an extrapolation" refers to the non-statistical considerations and assumptions needed when using surrogate endpoints to evaluate a new treatment. "Decision analysis to the rescue" refers to use the use of decision analysis to evaluate an additional prognostic marker because it is not possible to choose between purely statistical measures of marker performance. "The appeal of simplicity" refers to a straightforward and efficient use of a single randomized trial to evaluate overall treatment effect and treatment effect within subgroups using predictive markers. The simple themes provide a general guideline for evaluation of surrogate endpoints, prognostic markers, and predictive markers. © The Author(s) 2014.
A reliability analysis of cardiac repolarization time markers.
Scacchi, S; Franzone, P Colli; Pavarino, L F; Taccardi, B
2009-06-01
Only a limited number of studies have addressed the reliability of extracellular markers of cardiac repolarization time, such as the classical marker RT(eg) defined as the time of maximum upslope of the electrogram T wave. This work presents an extensive three-dimensional simulation study of cardiac repolarization time, extending the previous one-dimensional simulation study of a myocardial strand by Steinhaus [B.M. Steinhaus, Estimating cardiac transmembrane activation and recovery times from unipolar and bipolar extracellular electrograms: a simulation study, Circ. Res. 64 (3) (1989) 449]. The simulations are based on the bidomain - Luo-Rudy phase I system with rotational fiber anisotropy and homogeneous or heterogeneous transmural intrinsic membrane properties. The classical extracellular marker RT(eg) is compared with the gold standard of fastest repolarization time RT(tap), defined as the time of minimum derivative during the downstroke of the transmembrane action potential (TAP). Additionally, a new extracellular marker RT90(eg) is compared with the gold standard of late repolarization time RT90(tap), defined as the time when the TAP reaches 90% of its resting value. The results show a good global match between the extracellular and transmembrane repolarization markers, with small relative mean discrepancy (
[Prognostic and predictive molecular markers for urologic cancers].
Hartmann, A; Schlomm, T; Bertz, S; Heinzelmann, J; Hölters, S; Simon, R; Stoehr, R; Junker, K
2014-04-01
Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.
Martínez-Sánchez, Sara María; Minguela, Alfredo; Prieto-Merino, David; Zafrilla-Rentero, María Pilar; Abellán-Alemán, José; Montoro-García, Silvia
2017-01-01
Background and aims: Dietary studies have shown that active biopeptides provide protective health benefits, although the mediating pathways are somewhat uncertain. To throw light on this situation, we studied the effects of consuming Spanish dry-cured ham on platelet function, monocyte activation markers and the inflammatory status of healthy humans with pre-hypertension. Methods: Thirty-eight healthy volunteers with systolic blood pressure of >125 mmHg were enrolled in a two-arm crossover randomized controlled trial. Participants received 80 g/day dry-cured pork ham of >11 months proteolysis or 100 g/day cooked ham (control product) for 4 weeks followed by a 2-week washout before “crossing over” to the other treatment for 4 more weeks. Soluble markers and cytokines were analyzed by ELISA. Platelet function was assessed by measuring P-selectin expression and PAC-1 binding after ADP (adenosine diphosphate) stimulation using whole blood flow cytometry. Monocyte markers of the pathological status (adhesion, inflammatory and scavenging receptors) were also measured by flow cytometry in the three monocyte subsets after the interventional period. Results: The mean differences between dry-cured ham and cooked ham followed by a time period adjustment for plasmatic P-selectin and interleukin 6 proteins slightly failed (p = 0.062 and p = 0.049, respectively), notably increased for MCP-1 levels (p = 0.023) while VCAM-1 was not affected. Platelet function also decreased after ADP stimulation. The expression of adhesion and scavenging markers (ICAM1R, CXCR4 and TLR4) in the three subsets of monocytes was significantly higher (all p < 0.05). Conclusions: The regular consumption of biopeptides contained in the dry-cured ham but absent in cooked ham impaired platelet and monocyte activation and the levels of plasmatic P-selectin, MCP-1 and interleukin 6 in healthy subjects. This study strongly suggests the existence of a mechanism that links dietary biopeptides and beneficial
Deftereos, Spyridon; Giannopoulos, Georgios; Kossyvakis, Charalampos; Raisakis, Konstantinos; Kaoukis, Andreas; Driva, Metaxia; Ntzouvara, Olga; Panagopoulou, Vasiliki; Rentoukas, Ilias; Nikas, Dimitrios J; Pyrgakis, Vlasios; Alpert, Martin A
2009-09-01
The effects of radiographic contrast media on markers of complement activation and apoptosis in patients with chronic coronary artery disease (CAD) are unknown. The purpose of this study was to assess the comparative effects of ionic high-osmolar and non-ionic iso-osmolar radiographic contrast media on plasma markers of complement activation and apoptosis in patients with chronic CAD undergoing coronary angiography. Forty-four patients undergoing coronary angiography for chronic CAD were randomly assigned to receive the ionic high-osmolar radiographic contrast agent diatrizoate (Group A), or the non-ionic iso-osmolar contrast agent iodixanol (Group B) during angiography. Complement component 5 (C5a) and apoptotic markers sFas and sFasL were measured just prior to angiography and 1 hour after completion of angiography. Comparison of mean pre- and post-angiography plasma marker levels showed significantly greater increases in plasma levels in Group A than in Group B of C5a (29.30 +/- 5.45 ng/ml for Group A and 0.47 +/- 0.70 ng/ml for Group B (p < 0.00001), sFas (2.36 +/- 1.63 ng/ml for Group A and 0.23 +/- 0.90 ng/ml for Group B (p < 0.00001) and sFasL (14.00 +/- 5.41 pg/ml for Group A and 0.01 +/- 1.00 pg/ml for Group B (p < 0.00001). The results suggest that in patients with chronic CAD, the use of ionic high-osmolar radiographic contrast media during coronary angiography is associated with a more robust inflammatory and apoptotic milieu than that associated with the use of non-ionic iso-osmolar radiographic contrast media.
Kanzawa, Maki; Hara, Shigeo; Semba, Shuho; Yokozaki, Hiroshi; Hirokawa, Mitsuyoshi; Itoh, Tomoo
2014-04-01
Sorting nexins (SNXs) are a large, diverse group of cytoplasmic and membrane-associated proteins that function in a variety of cellular processes, including endocytosis, protein trafficking, and the retrieval of transmembrane proteins. In this study, we demonstrated that SNX2 is expressed in columnar and active thyroid follicular cells but not in flattened inactive thyrocytes. Morphometric analysis revealed a significant correlation between SNX2 positivity and columnar cell morphology. Immunohistochemical staining of serial sections of the thyroid tissue indicated that SNX2 localization was similar to sortilin, a protein expressed by active thyrocytes. Expression of SNX2 in thyrocytes is particularly marked and extensive in most hyperstimulated thyroid disorders, including Graves disease (diffusely SNX2 positive in 73.3% patients) and functioning nodules (93.8% patients). SNX2 immunolocalization in hyperstimulated follicular epithelial cells was specific among the SNXs family members examined. These results support the utility of SNX2 as a novel marker of active thyrocytes and reflect the endosomal trafficking activity in these cells.
Aydemir, Ömer; Çubukçuoğlu, Zeynep; Erdin, Soner; Taş, Cumhur; Onur, Ece; Berk, Michael
2014-01-01
This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502); household activities and superoxide dismutase (r = 0.501); participation in social activities and nitric oxide (r = 0.414); hobbies and leisure time activities and total glutathione (r = -0.567), superoxide dismutase (r = 0.667), and neurotrophin 4 (r = 0.450); and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597). There was no correlation between other domains of psychosocial functioning and oxidative stress markers. These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker.
Association between passive smoking and salivary markers related to periodontitis.
Nishida, Nobuko; Yamamoto, Yumiko; Tanaka, Muneo; Maeda, Kazuhiko; Kataoka, Kosuke; Nakayama, Kunio; Morimoto, Kanehisa; Shizukuishi, Satoshi
2006-10-01
The mechanism of passive smoking in terms of development of periodontitis has not been investigated. This study examined the effect of passive smoking on salivary markers related to periodontitis. Periodontal status was evaluated on the basis of probing pocket depth and clinical attachment level in 273 workers. Salivary marker levels were determined by enzyme assay including enzyme-linked immunosorbent assay. Six periodontal pathogens in saliva were assessed using real-time PCR methodology. Non-, passive and active smokers were defined as subjects exhibiting salivary cotinine levels of 0 (53 subjects), 1-7 (118) and > or = 8 ng/ml (102). Levels of salivary markers, including IL-1beta, lactoferrin, albumin and aspartate aminotransferase (AST), were elevated significantly in passive smokers relative to non-smokers. Additionally, these marker levels, with the exception of IL-1beta, decreased significantly in active smokers in comparison with passive smokers. However, no meaningful differences in percentages of periodontal pathogens were observed between non- and passive smokers. Multiple linear regression analyses were performed for each marker utilizing age, gender, cotinine level and periodontal status as independent variables. IL-1beta, albumin and AST were independently associated with cotinine level. Passive smoke exposure leads to elevation of IL-1beta, albumin and AST levels in saliva.
HIV-1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment
Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W.; Gisslén, Magnus
2010-01-01
Background. Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Methods. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Results. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54–213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Conclusions. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice. PMID:21050119
HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.
Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus
2010-12-15
Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54-213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.
Brown, Rachael; James, Cheree; Henderson, Luke A; Macefield, Vaughan G
2012-01-01
The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged images from the International Affective Picture System (IAPS). SSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively charged images (erotica) or negatively charged images (mutilation) were presented in blocks of fifteen images of a specific type, each block lasting 2 min. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing.
Correcting for deformation in skin-based marker systems.
Alexander, E J; Andriacchi, T P
2001-03-01
A new technique is described that reduces error due to skin movement artifact in the opto-electronic measurement of in vivo skeletal motion. This work builds on a previously described point cluster technique marker set and estimation algorithm by extending the transformation equations to the general deformation case using a set of activity-dependent deformation models. Skin deformation during activities of daily living are modeled as consisting of a functional form defined over the observation interval (the deformation model) plus additive noise (modeling error). The method is described as an interval deformation technique. The method was tested using simulation trials with systematic and random components of deformation error introduced into marker position vectors. The technique was found to substantially outperform methods that require rigid-body assumptions. The method was tested in vivo on a patient fitted with an external fixation device (Ilizarov). Simultaneous measurements from markers placed on the Ilizarov device (fixed to bone) were compared to measurements derived from skin-based markers. The interval deformation technique reduced the errors in limb segment pose estimate by 33 and 25% compared to the classic rigid-body technique for position and orientation, respectively. This newly developed method has demonstrated that by accounting for the changing shape of the limb segment, a substantial improvement in the estimates of in vivo skeletal movement can be achieved.
Aziz, Najib
2015-01-01
Measurement of circulating cytokine levels can provide important information in the study of the pathogenesis of disease. John L. Fahey was a pioneer in the measurement of circulating cytokines and immune-activation markers and a leader in the quality assessment/control of assays for measurement of circulating cytokines. Insights into the measurement of circulating cytokines, including consideration of multiplex assays, are presented here.
Demir, N; Nadaroglu, H; Gungor, A A; Demir, Y
2015-01-01
The influence of prostatic acid phosphatase (PAP) and human chorionic gonadotropin (HCG), tumor markers have been investigated on human erythrocyte carbonic anhydrase (HCA-I and HCA-II) and bovine erythrocyte (BCA) and bovine lung carbonic anhydrase (CA-IV) in vitro. Tumor markers are substances that can often be detected in higher-than-normal amounts in the blood, urine, or body tissues of some patients with certain types of cancer. Tumor markers are produced either by the tumor itself or by the body in response to the presence of cancer or certain benign (noncancerous) conditions. In addition to their role in cancer diagnosis, some tumor marker levels are measured before treatment to help doctors plan appropriate therapy. All of the tumor markers were determined to have inhibition effect, on human CA-I, CA-II, bovine erythrocyte CA (BCA) and bovine lung CA-IV isoenzymes. The effect of each tumor marker on CA was investigated by Wilbur-Andersen method modified by Rickly et al Inhibition effects of two different tumor markers on human CA-I, CA-II, bovine erythrocyte CA (BCA) and bovine lung CA-IV isoenzymes were determined by using the CO2-Hydratase method by plotting activity % vs (tumor markers). I50 values of tumor markers exhibiting inhibition effects were found by means of these graphs (Tab.1, Fig. 2, Ref. 20).
Lignans from Carthamus tinctorius suppress tryptophan breakdown via indoleamine 2,3-dioxygenase
Kuehnl, Susanne; Schroecksnadel, Sebastian; Temml, Veronika; Gostner, Johanna M.; Schennach, Harald; Schuster, Daniela; Schwaiger, Stefan; Rollinger, Judith M.; Fuchs, Dietmar; Stuppner, Hermann
2013-01-01
Seed extracts of Carthamus tinctorius L. (Asteraceae), safflower, have been traditionally used to treat coronary disease, thrombotic disorders, and menstrual problems but also against cancer and depression. A possible effect of C. tinctorius compounds on tryptophan-degrading activity of enzyme indoleamine 2,3-dioxygenase (IDO) could explain many of its activities. To test for an effect of C. tinctorius extracts and isolated compounds on cytokine-induced IDO activity in immunocompetent cells in vitro methanol and ethylacetate seed extracts were prepared from cold pressed seed cakes of C. tinctorius and three lignan derivatives, trachelogenin, arctigenin and matairesinol were isolated. The influence on tryptophan breakdown was investigated in peripheral blood mononuclear cells (PBMCs). Effects were compared to neopterin production in the same cellular assay. Both seed extracts suppressed tryptophan breakdown in stimulated PBMC. The three structurally closely related isolates exerted differing suppressive activity on PBMC: arctigenin (IC50 26.5 μM) and trachelogenin (IC50 of 57.4 μM) showed higher activity than matairesinol (IC50 >200 μM) to inhibit tryptophan breakdown. Effects on neopterin production were similar albeit generally less strong. Data show an immunosuppressive property of compounds which slows down IDO activity. The in vitro results support the view that some of the anti-inflammatory, anti-cancer and antidepressant properties of C. tinctorius lignans might relate to their suppressive influence on tryptophan breakdown. PMID:23867649
Evaluating surrogate endpoints, prognostic markers, and predictive markers — some simple themes
Baker, Stuart G.; Kramer, Barnett S.
2014-01-01
Background A surrogate endpoint is an endpoint observed earlier than the true endpoint (a health outcome) that is used to draw conclusions about the effect of treatment on the unobserved true endpoint. A prognostic marker is a marker for predicting the risk of an event given a control treatment; it informs treatment decisions when there is information on anticipated benefits and harms of a new treatment applied to persons at high risk. A predictive marker is a marker for predicting the effect of treatment on outcome in a subgroup of patients or study participants; it provides more rigorous information for treatment selection than a prognostic marker when it is based on estimated treatment effects in a randomized trial. Methods We organized our discussion around a different theme for each topic. Results “Fundamentally an extrapolation” refers to the non-statistical considerations and assumptions needed when using surrogate endpoints to evaluate a new treatment. “Decision analysis to the rescue” refers to use the use of decision analysis to evaluate an additional prognostic marker because it is not possible to choose between purely statistical measures of marker performance. “The appeal of simplicity” refers to a straightforward and efficient use of a single randomized trial to evaluate overall treatment effect and treatment effect within subgroups using predictive markers. Conclusion The simple themes provide a general guideline for evaluation of surrogate endpoints, prognostic markers, and predictive markers. PMID:25385934
Iba, Toshiaki; Gando, Satoshi; Murata, Atsuo; Kushimoto, Shigeki; Saitoh, Daizoh; Eguchi, Yutaka; Ohtomo, Yasuhiro; Okamoto, Kohji; Koseki, Kazuhide; Mayumi, Toshihiko; Ikeda, Toshiaki; Ishhikura, Hiroyasu; Ueyama, Masashi; Ogura, Yuji; Endo, Shigeatsu; Shimazaki, Shuji
2007-11-01
The changes in biomarkers of coagulation or fibrinolysis, anticoagulation, inflammation, and endothelial damage occur in patients with systemic inflammatory response syndrome (SIRS). The purpose of this study is to assess the prognostic value of these markers in patients with SIRS-associated hypercoagulopathy. Sixty-six SIRS patients with a platelet count less than 15.0 x 10(4)/mm3 in three university hospital intensive care units were enrolled in this prospective, comparative study. Blood samples were obtained on day 0 and day 2. Twelve hemostatic, inflammatory, and vascular endothelial indices were measured and the data were compared between the severe group (patients with a total maximum Sequential Organ Failure Assessment score of 10 or more and nonsurvivors; n = 25) and the less-severe group (Sequential Organ Failure Assessment score <10; n = 41). Significant changes between the groups were observed in platelet count, fibrin or fibrinogen degradation products, interleukin-6, soluble thrombomodulin, antithrombin (AT) activity, and protein C activity, both on day 0 and on day 2. In contrast, the d-dimer, soluble fibrin, plasmin-[alpha]2-antiplasmin complex, and E-selectin levels were higher in the severe group only on day 2. No significant difference was seen regarding the thrombin-AT complex and total plasminogen activator inhibitor on both days. A comparison of the areas under the receiver operating characteristic curve revealed the AT activity to be the best predictor of a progression of organ dysfunction. The changes in some hemostatic molecular markers and vascular endothelial markers were conspicuous in patients with organ dysfunction. The AT activity is considered to be the most useful predictor of organ dysfunction.
Gao, Yong-Jing; Ji, Ru-Rong
2009-01-01
c-Fos, the protein of the protooncogene c-fos, has been extensively used as a marker for the activation of nociceptive neurons in the spinal cord for more than twenty years since Hunt et al. first reported that peripheral noxious stimulation to a hind paw of rats leads to a marked induction of c-Fos in superficial and deep dorsal horn neurons in 1987. In 1999, Ji et al. reported that phosphorylated extracellular signal-regulated kinase (pERK) is specifically induced by noxious stimulation in superficial dorsal horn neurons. Accumulating evidence indicates that pERK induction or ERK activation in dorsal horn neurons is essential for the development of central sensitization, increased sensitivity of dorsal horn neurons that is responsible for the generation of persistent pain. Further, molecular mechanisms underlying ERK-mediated central sensitization have been revealed. In contrast, direct evidence for c-Fos-mediated central sensitization is not sufficient. After a noxious stimulus (e.g., capsaicin injection) or tissue injury, c-Fos begins to be induced after 30-60 minutes, whereas pERK can be induced within a minute, which can correlate well with the development of pain hypersensitivity. While c-Fos is often induced in the nuclei of neurons, pERK can be induced in different subcellular structures of neurons such as nuclei, cytoplasma, axons, and dendrites. pERK can even be induced in spinal cord microglia and astrocytes after nerve injury. In summary, both c-Fos and pERK can be used as markers for neuronal activation following noxious stimulation and tissue injury, but pERK is much more dynamic and appears to be a better marker for central sensitization. PMID:19898681
Antiorthostatic suspension stimulates profiles of macrophage activation in mice
NASA Technical Reports Server (NTRS)
Miller, E. S.; Bates, R. A.; Koebel, D. A.; Sonnenfeld, G.
1999-01-01
The antiorthostatic suspension model simulates certain physiological effects of spaceflight. We have previously reported BDF1 mice suspended by the tail in the antiorthostatic orientation for 4 days express high levels of resistance to virulent Listeria monocytogenesinfection. In the present study, we examined whether the increased resistance to this organism correlates with profiles of macrophage activation, given the role of the macrophage in killing this pathogen in vivo. We infected BDF1 mice with a lethal dose of virulent L. monocytogenes on day 4 of antiorthostatic suspension and 24 h later constructed profiles of macrophage activation. Viable listeria could not be detected in mice suspended in the antiorthostatic orientation 24 h after infection. Flow cytometric analysis revealed the numbers of granulocytes and mononuclear phagocytes in the spleen of infected mice were not significantly altered as a result of antiorthostatic suspension. Splenocytes from antiorthostatically suspended infected mice produced increased titers of IL-1. Serum levels of neopterin, a nucleotide metabolite secreted by activated macrophages, were enhanced in mice infected during antiorthostatic suspension, but not in antiorthostatically suspended naive mice. Splenic macrophages from mice infected on day 4 of suspension produced enhanced levels of lysozyme. In contrast to the results from antiorthostatically suspended infected mice, macrophages from antiorthostatically suspended uninfected mice did not express enhanced bactericidal activities. The collective results indicate that antiorthostatic suspension can stimulate profiles of macrophage activation which correlate with increased resistance to infection by certain classes of pathogenic bacteria.
Farpour-Lambert, Nathalie J; Aggoun, Yacine; Marchand, Laetitia M; Martin, Xavier E; Herrmann, François R; Beghetti, Maurice
2009-12-15
The aim of this study was to determine the effects of physical activity on systemic blood pressure (BP) and early markers of atherosclerosis in pre-pubertal obese children. Hypertension and endothelial dysfunction are premature complications of obesity. We performed a 3-month randomized controlled trial with a modified crossover design: 44 pre-pubertal obese children (age 8.9 + or - 1.5 years) were randomly assigned (1:1) to an exercise (n = 22) or a control group (n = 22). We recruited 22 lean children (age 8.5 + or - 1.5 years) for baseline comparison. The exercise group trained 60 min 3 times/week during 3 months, whereas control subjects remained relatively inactive. Then, both groups trained twice/week during 3 months. We assessed changes at 3 and 6 months in office and 24-h BP, arterial intima-media thickness (IMT) and stiffness, endothelial function (flow-mediated dilation), body mass index (BMI), body fat, cardiorespiratory fitness (maximal oxygen consumption [VO(2)max]), physical activity, and biological markers. Obese children had higher BP, arterial stiffness, body weight, BMI, abdominal fat, insulin resistance indexes, and C-reactive protein levels, and lower flow-mediated dilation, VO(2)max, physical activity, and high-density lipoprotein cholesterol levels than lean subjects. At 3 months, we observed significant changes in 24-h systolic BP (exercise -6.9 + or - 13.5 mm Hg vs. control 3.8 + or - 7.9 mm Hg, -0.8 + or - 1.5 standard deviation score [SDS] vs. 0.4 + or - 0.8 SDS), diastolic BP (-0.5 + or - 1.0 SDS vs. 0 + or - 1.4 SDS), hypertension rate (-12% vs. -1%), office BP, BMI z-score, abdominal fat, and VO(2)max. At 6 months, change differences in arterial stiffness and IMT were significant. A regular physical activity program reduces BP, arterial stiffness, and abdominal fat; increases cardiorespiratory fitness; and delays arterial wall remodeling in pre-pubertal obese children. (Effects of Aerobic Exercise Training on Arterial Function and
Genomic markers for decision making: what is preventing us from using markers?
Coyle, Vicky M; Johnston, Patrick G
2010-02-01
The advent of novel genomic technologies that enable the evaluation of genomic alterations on a genome-wide scale has significantly altered the field of genomic marker research in solid tumors. Researchers have moved away from the traditional model of identifying a particular genomic alteration and evaluating the association between this finding and a clinical outcome measure to a new approach involving the identification and measurement of multiple genomic markers simultaneously within clinical studies. This in turn has presented additional challenges in considering the use of genomic markers in oncology, such as clinical study design, reproducibility and interpretation and reporting of results. This Review will explore these challenges, focusing on microarray-based gene-expression profiling, and highlights some common failings in study design that have impacted on the use of putative genomic markers in the clinic. Despite these rapid technological advances there is still a paucity of genomic markers in routine clinical use at present. A rational and focused approach to the evaluation and validation of genomic markers is needed, whereby analytically validated markers are investigated in clinical studies that are adequately powered and have pre-defined patient populations and study endpoints. Furthermore, novel adaptive clinical trial designs, incorporating putative genomic markers into prospective clinical trials, will enable the evaluation of these markers in a rigorous and timely fashion. Such approaches have the potential to facilitate the implementation of such markers into routine clinical practice and consequently enable the rational and tailored use of cancer therapies for individual patients.
Wormley, Floyd L.; Chaiban, Joseph; Fidel, Paul L.
2001-01-01
Cell-mediated immunity by Th1-type CD4+ T cells is the predominant host defense mechanism against mucosal candidiasis. However, studies using an estrogen-dependent murine model of vaginal candidiasis have demonstrated little to no change in resident vaginal T cells during infection and no systemic T-cell infiltration despite the presence of Candida-specific systemic Th1-type responses in infected mice. The present study was designed to further investigate these observations by characterizing T-cell activation and cell adhesion molecule expression during primary and secondary C. albicans vaginal infections. While flow cytometry analysis of activation markers showed some evidence for activation of CD3+ draining lymph node and/or vaginal lymphocytes during both primary and secondary vaginal Candida infection, CD3+ cells expressing the homing receptors and integrins α4β7, αM290β7, and α4β1 in draining lymph nodes of mice with primary and secondary infections were reduced compared to results for uninfected mice. At the local level, few vaginal lymphocytes expressed integrins, with only minor changes observed during both primary and secondary infections. On the other hand, immunohistochemical analysis of vaginal cell adhesion molecule expression showed increases in mucosal addressin cell adhesion molecule 1 and vascular cell adhesion molecule 1 expression during both primary and secondary infections. Altogether, these data suggest that although the vaginal tissue is permissive to cellular infiltration during a vaginal Candida infection, the reduced numbers of systemic cells expressing the reciprocal cellular adhesion molecules may preempt cellular infiltration, thereby limiting Candida-specific T-cell responses against infection. PMID:11447188
Li, Ziqiang; Liu, Jia; Li, Yazhuo; Du, Xi; Li, Yanfen; Wang, Ruihua; Lv, Chunxiao; He, Xin; Wang, Baohe; Huang, Yuhong; Zhang, Deqin
2018-06-01
A quality marker (Q-marker) is defined as an inherent chemical compound that is used for the quality control of a drug. Its biological activities are closely related to safety and therapeutic effects. Generally, a multiple-component herbal medicine may have many Q-markers. We therefore proposed a concept of "super Q-marker" satisfying both the criterion of Q-markers and PK-markers to be used in more effective quality control of herbal medicine. The first aim was to find suitable prototype-based PK-markers from Tangzhiqing tablets (TZQ), a Chinese patent medicine. Then super Q-markers were expected to be identified from the prototype-based PK-markers based on an in vitro-in vivo correlation study. Potentially eligible prototype-based PK-markers were identified in a single- and multiple-dose pharmacokinetic study on TZQ in 30 healthy volunteers. The in vitro dissolution and permeation profiles of the prototype-based PK-markers of TZQ were evaluated by the physiologically-based drug dissolution/absorption simulating system (DDASS). An in vitro-in vivo correlation analysis was conducted between the dissolution/permeation behaviors in DDASS and the actual absorption profiles in human to test the transferability and traceability of the promising super Q-markers for TZQ. In human, plasma paeoniflorin and nuciferine as prototype-based PK-markers exhibited the appropriate pharmacokinetic properties, including dose-dependent systemic exposure (AUC, C max ) and a proper elimination half-life (1∼3h). In DDASS, it was predicted that paeoniflorin and nuciferine are highly permeable but the absorption rates are primarily limited by the dissolution rates. Moreover, the established in vitro-in vivo correlations of paeoniflorin and nuciferine were in support of the super Q-markers features. Paeoniflorin and nuciferine are identified as the super Q-markers from the prototype-based PK-markers of TZQ based on findings from a combination of in vitro, in vivo, and in vitro-in vivo
Sympathetic arousal as a marker of chronicity in childhood stuttering.
Zengin-Bolatkale, Hatun; Conture, Edward G; Walden, Tedra A; Jones, Robin M
2018-01-01
This study investigated whether sympathetic activity during a stressful speaking task was an early marker for stuttering chronicity. Participants were 9 children with persisting stuttering, 23 children who recovered, and 17 children who do not stutter. Participants performed a stress-inducing picture-naming task and skin conductance was measured across three time points. Findings indicated that at the initial time point, children with persisting stuttering exhibited higher sympathetic arousal during the stressful speaking task than children whose stuttering recovered. Findings are taken to suggest that sympathetic activity may be an early marker of heightened risk for chronic stuttering.
Kupchak, Brian R; Kraemer, William J; Hooper, David R; Saenz, Cathy; Dulkis, Lexie L; Secola, Paul J; Brown, Lee E; Galpin, Andrew J; Coburn, Jared W; DuPont, William H; Caldwell, Lydia K; Volek, Jeff S; Maresh, Carl M
2017-01-01
Athletes and military service members are known to undergo strenuous exercise and sometimes have to take long haul flights soon afterwards; however, its combined effect on many physiological functions is relatively unknown. Therefore, we examined the combined effects of a full-body muscle-damaging workout and transcontinental flight on coagulation and fibrinolysis in healthy, resistance trained men. We also determined the efficacy of a full-body compression garment in limiting their coagulation responses. Nineteen healthy, resistance trained men flew from Connecticut (CT) to California (CA), performed a full-body muscle-damaging workout and then flew back to CT. Ten participants wore full-body compression garments (FCG) for the duration of both flights and during all other portions of the study except during workouts and blood draws, when they wore loose clothing. Nine controls wore loose clothing (CON) throughout the study. Blood samples were collected at 16 h and 3 h before the initial flight from CT, immediately after landing in CA, immediately before and immediately after the full-body workout in CA, immediately after landing in CT, and at 29 h after landing in CT. Plasma markers of coagulation included activated partial thromboplastin time (aPTT), prothrombin fragment 1+2 (PTF 1+2) and thrombin ant-thrombin (TAT). Markers of the fibrinolytic system included the tissue plasmigen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and D-Dimer. Both FCG and CON groups exhibited a faster aPTT after the full-body workout compared to all other time points. Thrombin generation markers, TAT and PTF 1+2, increased significantly after the full-body workout and immediately after landing in CT. Additionally, tPA increased after the full-body workout, while PAI-1 increased before the flight to CA, after the full-body workout, and just after landing in CT. The D-Dimer significantly increased after the full-body workout and at 29 h post-flight in both groups
Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease.
Campolo, Jonica; De Maria, Renata; Cozzi, Lorena; Parolini, Marina; Bernardi, Stefano; Proserpio, Paola; Nobili, Lino; Gelosa, Giorgio; Piccolo, Immacolata; Agostoni, Elio C; Trivella, Maria G; Marraccini, Paolo
2016-11-15
We explored the role of oxidative stress and inflammatory molecules as potential Parkinson (PD) biomarkers and correlated biological with non-motor abnormalities (olfactory impairment and dysautonomia), in patients with idiopathic REM behavior disorder (iRBD) (prodromal PD) and established PD. We recruited 11 iRBD and 15 patients with idiopathic PD (Hohen&Yahr 1-3, on L-DOPA and dopamine agonists combination therapy) and 12 age- and sex-matched controls (CTRL). We measured total olfactory score (TOS), autonomic function [deep breathing (DB), lying to standing (LS) and Valsalva manoeuvre (VM) ratios], blood reduced glutathione (Br-GSH), oxidative stress and inflammatory markers (neopterin). Anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but absent in CTRL. Orthostatic hypotension was more common among iRBD (73%) and PD (60%) than in CTRL (25%). By univariable ordinal logistic regression, TOS, Br-GSH, LS and VM ratio worsened from CTRL to iRBD and PD groups. Only reduced Br-GSH levels (p=0.037, OR=0.994; 95%CI 0.988-1.000) were independently associated to PD. TOS correlated with Br-GSH (R=0.34, p=0.037), VM ratio (R=0.43, p=0.015), and neopterin (rho=0.39, p=0.016). Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular dysautonomia, a useful biomarker for an integrative, early diagnosis of PD. Copyright © 2016 Elsevier B.V. All rights reserved.
Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.
Delille, Cecile A; Pruett, Sarah T; Marconi, Vincent C; Lennox, Jeffrey L; Armstrong, Wendy S; Arrendale, Richard F; Sheth, Anandi N; Easley, Kirk A; Acosta, Edward P; Vunnava, Aswani; Ofotokun, Ighovwerha
2014-09-01
HIV-1 protease inhibitors (PIs) exhibit different protein binding affinities and achieve variable plasma and tissue concentrations. Degree of plasma protein binding may impact central nervous system penetration. This cross-sectional study assessed cerebrospinal fluid (CSF) unbound PI concentrations, HIV-1 RNA, and neopterin levels in subjects receiving either ritonavir-boosted darunavir (DRV), 95% plasma protein bound, or atazanavir (ATV), 86% bound. Unbound PI trough concentrations were measured using rapid equilibrium dialysis and liquid chromatography/tandem mass spectrometry. Plasma and CSF HIV-1 RNA and neopterin were measured by Ampliprep/COBAS® Taqman® 2.0 assay (Roche) and enzyme-linked immunosorbent assay (ALPCO), respectively. CSF/plasma unbound drug concentration ratio was higher for ATV, 0.09 [95% confidence interval (CI) 0.06-0.12] than DRV, 0.04 (95%CI 0.03-0.06). Unbound CSF concentrations were lower than protein adjusted wild-type inhibitory concentration-50 (IC50 ) in all ATV and 1 DRV-treated subjects (P < 0.001). CSF HIV-1 RNA was detected in 2/15 ATV and 4/15 DRV subjects (P = 0.65). CSF neopterin levels were low and similar between arms. ATV relative to DRV had higher CSF/plasma unbound drug ratio. Low CSF HIV-1 RNA and neopterin suggest that both regimens resulted in CSF virologic suppression and controlled inflammation. © 2014, The American College of Clinical Pharmacology.
Effect of Protein Binding on Unbound Atazanavir and Darunavir Cerebrospinal Fluid Concentrations
Delille, Cecile A.; Pruett, Sarah T.; Marconi, Vincent C.; Lennox, Jeffrey L.; Armstrong, Wendy S.; Arrendale, Richard F.; Sheth, Anandi N.; Easley, Kirk A.; Acosta, Edward P.; Vunnava, Aswani; Ofotokun, Ighovwerha
2015-01-01
HIV-1 protease inhibitors (PIs) exhibit different protein binding affinities and achieve variable plasma and tissue concentrations. Degree of plasma protein binding may impact central nervous system penetration. This cross-sectional study assessed cerebrospinal fluid (CSF) unbound PI concentrations, HIV-1 RNA, and neopterin levels in subjects receiving either ritonavir-boosted darunavir (DRV), 95% plasma protein bound, or atazanavir (ATV), 86% bound. Unbound PI trough concentrations were measured using rapid equilibrium dialysis and liquid chromatography/tandem mass spectrometry. Plasma and CSF HIV-1 RNA and neopterin were measured by Ampliprep/COBAS® Taqman® 2.0 assay (Roche) and enzyme-linked immunosorbent assay (ALPCO), respectively. CSF/plasma unbound drug concentration ratio was higher for ATV, 0.09 [95% confidence interval (CI) 0.06–0.12] than DRV, 0.04 (95%CI 0.03–0.06). Unbound CSF concentrations were lower than protein adjusted wild-type inhibitory concentration-50 (IC50) in all ATV and 1 DRV-treated subjects (P < 0.001). CSF HIV-1 RNA was detected in 2/15 ATV and 4/15 DRV subjects (P = 0.65). CSF neopterin levels were low and similar between arms. ATV relative to DRV had higher CSF/plasma unbound drug ratio. Low CSF HIV-1 RNA and neopterin suggest that both regimens resulted in CSF virologic suppression and controlled inflammation. PMID:24691856
Krause, Daniela; Stapf, Theresa M; Kirnich, Verena B; Hennings, Anika; Riemer, Sabine; Chrobok, Agnieszka; Fries, Daniel R; Pedrosa Gil, Francisco; Rief, Winfried; Schwarz, Markus J; Schmidmaier, Ralf
2018-06-12
Cellular immune status in major depression (MD) patients differs from that in somatoform disorder (SFD) patients and healthy controls (HC). It is still questionable whether the patterns of immune parameters remain stable over time. Therefore, we studied lymphocyte and monocyte cell counts and neopterin levels in peripheral blood of MD and SFD patients and HC over 12 weeks and tested for correlations between biochemical and psychometric parameters. Thirty-nine patients with MD, 27 with SFD, and 51 HC were recruited. Peripheral blood was drawn at four visits, at 4-week intervals. We assessed the total cell count of B lymphocytes, natural killer (NK) cells, T lymphocyte subpopu-lations, and monocytes by flow cytometry, and neopterin serum levels by ELISA. Psychometric parameters were measured with questionnaires. Counts of lymphocytes, monocytes, and neopterin were stable in the SFD and HC groups. In the MD group, total CD3+, CD3+CD8+, NK cells, and CD3+CD25+ T cells showed inhomogeneous variances in Friedman tests, particularly in females. Neopterin correlated with depressed mood in MD patients, and with body mass index in HC. Cellular immune parameters are stable in HC and SFD. Our results may indicate influences of MD and gender on some cellular immune parameters. This may need to be considered in future immunological studies. © 2018 S. Karger AG, Basel.
Park, So Youn; Shin, Hwa Kyoung; Lee, Jeong Hyun; Kim, Chi Dae; Lee, Won Suk; Rhim, Byung Yong; Hong, Ki Whan
2009-05-01
In a previous study, cilostazol promoted differentiation of 3T3-L1 fibroblasts into adipocytes and improved insulin sensitivity by stimulating peroxisome proliferator-activated receptor (PPAR) gamma transcription. This study evaluated the in vivo efficacy of cilostazol to protect a db/db mouse model of type 2 diabetes against altered metabolic abnormalities and proinflammatory markers via activation of PPARgamma transcription. Eight-week-old db/db mice were treated with cilostazol or rosiglitazone for 12 days. Cilostazol significantly decreased plasma glucose and triglyceride levels, as did rosiglitazone, a PPARgamma agonist. Elevated plasma insulin and resistin levels were significantly decreased by cilostazol, and decreased adiponectin mRNA expression was elevated along with increased plasma adiponectin. Cilostazol significantly increased both adipocyte fatty acid binding protein and fatty acid transport protein-1 mRNA expressions with increased glucose transport 4 in the adipose tissue. Cilostazol and rosiglitazone significantly suppressed proinflammatory markers (superoxide, tumor necrosis factor-alpha, and vascular cell adhesion molecule-1) in the carotid artery of db/db mice. In an in vitro study with 3T3-L1 fibroblasts, cilostazol significantly increased PPARgamma transcription activity, as did rosiglitazone. The transcription activity stimulated by cilostazol was attenuated by KT5720 [(9R,10S,12S)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9, 12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo [3,4-I][1,6]-benzodiazocine-10-carboxylic acid hexyl ester], a cAMP-dependent protein kinase inhibitor, and GW9662 (2-chloro-5-nitrobenzanilide), an antagonist of PPARgamma activity, indicative of implication of the phosphatidylinositol 3-kinase/Akt signal pathway. These results suggest that cilostazol may improve insulin sensitivity along with anti-inflammatory effects in type 2 diabetic patients via activation of both cAMP-dependent protein kinase and
Singh, Karn P; Kaushik, Ramakant; Garg, Veena; Sharma, Ruchi; George, Aman; Singh, Manoj K; Manik, Radhey S; Palta, Prabhat; Singla, Suresh K; Chauhan, Manmohan S
2012-12-01
In this study, we describe the production of buffalo parthenogenetic blastocysts and subsequent isolation of parthenogenetic embryonic stem cell (PGESC)-like cells. PGESC colonies exhibited dome-shaped morphology and were clearly distinguishable from the feeder layer cells. Different stages of development of parthenogenetic embryos and derived embryonic stem cell (ESC)-like cells expressed key ESC-specific markers, including OCT-4, NANOG, SOX-2, FOXD3, REX-1, STAT-3, TELOMERASE, NUCLEOSTEMIN, and cMYC. Immunofluorescence-based studies revealed that the PGESCs were positive for surface-based pluripotent markers, viz., SSEA-3, SSEA-4, TRA 1-80, TRA 1-60, CD-9, and CD-90 and exhibited high alkaline phosphatase (ALP) activity. PGEC cell-like cells formed embryoid body (EB)-like structures in hanging drop cultures and when cultured for extended period of time spontaneously differentiated into derivatives of three embryonic germ layers as confirmed by RT-PCR for ectodermal (CYTOKERATIN8, NF-68), mesodermal (MSX1, BMP-4, ASA), and endodermal markers (AFP, HNF-4, GATA-4). Differentiation of PGESCs toward the neuronal lineage was successfully directed by supplementation of serum-containing media with retinoic acid. Our results indicate that the isolated ESC-like cells from parthenogenetic blastocyst hold properties of ESCs and express markers of pluripotency. The pluripotency markers were also expressed by early cleavage-stage of buffalo embryos.
Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia
Swellam, Menha; Samy, Nervana; Abdl Wahab, Susan; Ibrahim, Mohamed Saeed
2009-01-01
Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations. Materials and methods: We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays. Results: Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P < 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy nonpregnant vs PE or normotensive pregnant vs PE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity. Conclusions: Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE. PMID:19597295
Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection
Ahlgren, Erika; Hagberg, Lars; Fuchs, Dietmar; Andersson, Lars-Magnus; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus
2016-01-01
Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = –0.41, p < 0.001) and folate (r = –0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals. PMID:27441551
Clinical markers of vitiligo activity.
Benzekri, Laila; Gauthier, Yvon
2017-05-01
Current modalities of understanding disease state (active/stable) are limited when considering treatment of vitiligo. We sought to develop a rapid, accurate, and noninvasive assessment of vitiligo state. In daylight and Wood's light examinations, 2 common clinical types of vitiligo were identified as amelanotic with sharply demarcated borders and hypomelanotic with poorly defined borders. Photographs were taken at the time of examination and a skin biopsy at the edge of a vitiligo lesion was performed. One year after the initial visit, the vitiligo was classified as stable if no new lesions had appeared, and as active if the number, size, or both of existing vitiligo lesions were increased. Skin biopsy specimens from 71 patients were stained and immunostained for melanocytes, CD8 + T lymphocytes, and E-cadherin. The active lesions were associated with hypomelanotic appearance with poorly defined borders (P < .001), and histologically with an infiltration of CD8 + T lymphocytes in the epidermis and dermis (P = .017), with a strong expression of E-cadherin (P = .044). The fact that this was a single-center study and that activity was sometimes site-dependent are limitations. The hypomelanotic with poorly defined borders type could be a good indicator of the actual activity of a vitiligo lesion. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Keane, N M; Price, P; Lee, S; Stone, S F; French, M A
2001-01-01
This study evaluates serum CD26 (dipeptidyl peptidase IV, DPPIV) enzyme activity and serum levels of soluble CD30 as markers of T1 and T2 cytokine environments in HIV patients who achieved immune reconstitution after highly active antiretroviral therapy (HAART). Patients who had experienced inflammatory disease associated with pre-existent opportunistic infections after HAART (immune restoration diseases, IRD) were considered separately. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were compared with IFN-γ production by PBMC cultured with cytomegalovirus (CMV) antigen in controls and patient groups. High sCD30 levels were associated with low IFN-γ production after antigenic stimulation in control subjects and, to a lesser extent, in immune reconstituted HIV patients. There was no association between serum CD26 (DPPIV) enzyme activity and IFN-γ production or sCD30 levels. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were significantly increased in immune reconstituted patients with high HIV viral loads. Patients who had experienced CMV retinitis as an IRD had significantly higher sCD30 levels than all other patient groups. Hence, high sCD30 levels may be a marker of a T2 cytokine environment in HIV patients with immune reconstitution and are associated with higher HIV viral loads and a history of CMV associated IRD. PMID:11678906
Cancer risk associated with chronic diseases and disease markers: prospective cohort study
Tu, Huakang; Wen, Chi Pang; Tsai, Shan Pou; Chow, Wong-Ho; Wen, Christopher; Ye, Yuanqing; Zhao, Hua; Tsai, Min Kuang; Huang, Maosheng; Dinney, Colin P; Tsao, Chwen Keng
2018-01-01
Abstract Objectives To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers. Design Prospective cohort study. Setting Standard medical screening program in Taiwan. Participants 405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years. Main outcome measures Cancer incidence and cancer mortality. Results A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among
CHANGES IN URINE MARKERS AND SYMPTOMS AFTER BLADDER DISTENTION FOR INTERSTITIAL CYSTITIS
Erickson, Deborah R.; Kunselman, Allen R.; Bentley, Christina M.; Peters, Kenneth M.; Rovner, Eric S.; Demers, Laurence M.; Wheeler, Marcia A.; Keay, Susan K.
2008-01-01
Purpose To evaluate changes in urine markers and symptom scores after bladder distention in interstitial cystitis (IC) patients. Materials and Methods Subjects were 33 new patients with no prior IC treatments. Urine specimens were taken before and one month after bladder distention. University of Wisconsin (UW) symptom scores were done the same day as the urine specimen collection. Urine marker levels and symptom scores before and after distention were compared. Changes in markers were tested for associations with changes in symptom scores and other markers. Pre-distention markers and specific pre-distention symptoms were tested for their association with post-distention symptom improvement. Results After distention, the median total UW score decreased significantly (28.5 before, 10 after, p<0.001). Twelve patients (36%) had at least 30% improvement in UW score, and eight patients (24%) had at least 50% improvement. No pre-distention markers or symptoms predicted which patients would have a good response. Two of the urine markers improved significantly after distention: anti-proliferative factor (APF) activity (median −96% before, −17% after, p< 0.001) and heparin binding-epidermal growth factor-like growth factor (HB-EGF) levels (median 0.34 ng/mg creatinine before, 4.1 after, p<0.001). None of the changes in urine markers associated with changes in symptom scores. Conclusions The median symptom score for newly diagnosed IC patients decreased after distention, but only a minority of patients had at least 30% symptom improvement. Bladder distention altered urine APF activity and HB-EGF levels towards normal, but the mechanism of symptom relief after distention is still unknown. PMID:17222633
Lee, Tsung-Hsien; Liu, Chung-Hsien; Shih, Yang-Tse; Tsao, Hui-Mei; Huang, Chun-Chia; Chen, Hsiu-Hui; Lee, Maw-Sheng
2010-04-01
Couples with unexplained infertility (UI) tend to have low fertilization rates with current IVF procedures. Here, we attempted to identify spermatozoa with apoptotic markers in couples with UI and unsuccessful intrauterine insemination (IUI) and we investigated the efficiency and benefit of magnetic-activated cell sorting (MACS) for sperm preparation in such patients. Sixty couples with UI and two IUI failures were recruited. The sperm were prepared by conventional density gradient centrifugation (DGC) and divided into two aliquots. One aliquot was used as a control and the other was further processed by MACS (D + M). Apoptotic markers were identified using fluorescence-labeled dye and flow cytometry, including externalization of phosphatidylserine (EPS), disrupted mitochondrial membrane potential (MMP) and DNA fragmentation. The fertilization potential of prepared spermatozoa was analyzed by basic semen analysis, computer-aided sperm analysis and the induced acrosome reaction test (IART). After DGC, spermatozoa showed 18.6% EPS, 28.3% disrupted MMP and 13.5% DNA fragmentation. Numbers of spermatozoa with apoptotic markers were significantly reduced by D + M, versus DGC alone (P < 0.001). Although the motility of spermatozoa was slightly decreased after MACS, most sperm motion characteristics were not impaired. Interestingly, the IART significantly improved after D + M, versus DGC alone, especially for the couples with a normal hemizona assay (P < 0.001). The spermatozoa prepared by D + M showed a reduced level of apoptotic markers. Improvement in the IART suggests a high fertilization potential of the processed spermatozoa. The identification of apoptotic markers and use of MACS may be helpful in directing the management plan for patients with UI and multiple IUI failures.
Crowell, Trevor A; Fletcher, James LK; Sereti, Irini; Pinyakorn, Suteeraporn; Dewar, Robin; Krebs, Shelly J; Chomchey, Nitiya; Rerknimitr, Rungsun; Schuetz, Alexandra; Michael, Nelson L; Phanuphak, Nittaya; Chomont, Nicolas; Ananworanich, Jintanat
2016-01-01
Introduction Colonic infiltration by HIV occurs soon after infection, establishing a persistent viral reservoir and a barrier to cure. We investigated virologic and immunologic correlates of detectable colonic HIV RNA during acute HIV infection (AHI) and their response to antiretroviral treatment (ART). Methods From 49,458 samples screened for HIV, 74 participants were enrolled during AHI and 41 consented to optional sigmoidoscopy, HIV RNA was categorized as detectable (≥50 copies/mg) or undetectable in homogenized colon biopsy specimens. Biomarkers and HIV burden in blood, colon and cerebrospinal fluid were compared between groups and after 24 weeks of ART. Results Colonic HIV RNA was detectable in 31 participants (76%) and was associated with longer duration since HIV exposure (median 16 vs. 11 days, p=0.02), higher median plasma levels of cytokines and inflammatory markers (CXCL10 476 vs. 148 pg/mL, p=0.02; TNF-RII 1036 vs. 649 pg/mL, p<0.01; neopterin 2405 vs. 1368 pg/mL, p=0.01) and higher levels of CD8+ T cell activation in the blood (human leukocyte antigen - antigen D related (HLA-DR)/CD38 expression 14.4% vs. 7.6%, p <0.01) and colon (8.9% vs. 4.5%, p=0.01). After 24 weeks of ART, participants with baseline detectable colonic HIV RNA demonstrated persistent elevations in total HIV DNA in colonic mucosal mononuclear cells (CMMCs) (median 61 vs. 0 copies/106 CMMCs, p=0.03) and a trend towards higher total HIV DNA in peripheral blood mononuclear cells (PBMC) (41 vs. 1.5 copies/106 PBMCs, p=0.06). There were no persistent differences in immune activation and inflammation. Conclusions The presence of detectable colonic HIV RNA at the time of ART initiation during AHI is associated with higher levels of proviral DNA after 24 weeks of treatment. Seeding of HIV in the gut may have long-lasting effects on the size of persistent viral reservoirs and may represent an important therapeutic target in eradication strategies. PMID:27637172
Sebeková, Katarína; Boor, Peter; Valachovicová, Martina; Blazícek, Pavol; Parrák, Vojtech; Babinská, Katarína; Heidland, August; Krajcovicová-Kudlácková, Marica
2006-09-01
Conditions predisposing to metabolic syndrome (MetS) are associated with increased oxidative stress and inflammation. We studied, in vegetarians (n = 90) and omnivores (n = 46), the impact of the dietary regimen on the occurrence of MetS risk factors (RFs: BMI, blood pressure, glucose metabolism and lipid profile) in relation to oxidative status (advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), malondialdehyde, ferric reducing ability of plasma, vitamins A, E, C, beta-carotene and superoxide dismutase activity) and microinflammation (C-reactive protein, leukocytes and neopterin). The proportion of subjects without/positive for one or two MetS RFs was comparable between the groups. From the components of MetS only immunoreactive insulin levels differed significantly (95% CI: omnivores: 5.0-7.1 microU/mL, vegetarians: 4.5-5.4, p = 0.03). Omnivores had lower AOPP (omnivores: 0.29-0.36 micromol/g albumin, vegetarians: 0.36-0.52, p = 0.01) and beta-carotene levels than vegetarians, they consumed more calories, proteins, fat and saturated fatty acids, and less fibres, beta-carotene and vitamin C. Multiple regression analysis revealed vitamin E and AOPP levels as the most important independent determinants of MetS RFs. The vegetarian diet seems to exert beneficial effects on MetS RFs associated microinflammation. Whether the vegetarian diet may counteract the deleterious effects of elevated AOPPs and AGEs, remains to be elucidated.
Santos, Clarcson P; Silva, Luciana F; Lopes, Marcelo B; Martins, Márcia T S; Kraychete, Angiolina C; Silva, Fernanda A; Martins, Maria T S; Matos, Cácia M; Lopes, Gildete B; Lopes, Antonio A
2017-11-24
Sedentariness, high inflammation status and malnutrition are highly prevalent in end-stage kidney disease patients on maintenance hemodialysis (MHD). This study investigated associations of weekly physical activity energy expenditure (PAEE) with clinical and anthropometric markers of nutrition and inflammation. The analysis was performed using baseline cross-sectional data of 640 patients enrolled in the prospective cohort "The Prospective Study of the Prognosis of Patients Treated Chronically by Hemodialysis" (PROHEMO) developed in Salvador, BA, Brazil. The long version of the International Physical Activity Questionnaire was used to determine a summary measure of PAEE, the metabolic equivalent of task (MET), taking into account physical activities related to occupation, recreation, travel, sports, and housework. PAEE was the predictor variable. To assess associations of PAEE with outcomes, the sex-age-specific median MET was used. The malnutrition-inflammation score (MIS) with range of 0 to 30 (higher is worse), conicity index as indicator of abdominal adiposity and C-reactive protein (CRP) were the nutritional-inflammatory outcomes. The mean age of the patients was 48.9 ± 13.8 y, 60.3% were males, 16.7% diabetic, 88.1% nonwhite. In multivariable logistic regression models with adjustments for sociodemographic variables and comorbidities, PAEE ≤median was associated with MIS ≥6 (odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.08, 2.29), conicity index ≥1.3 (OR = 1.52, 95% CI = 1.03, 2.23) and CRP >1.30 mg/dL (OR = 1.69, 95% CI = 1.08, 2.84). Greater physical activity assessed by PAEE was associated with indicators of better nutritional and inflammation status. These results indicate opportunities for improving outcomes in MHD patients by counseling and treatment intervention.
Salas, Carlos; Cristi-Montero, Carlos; Fan, Yu; Durán, Eliana; Labraña, Ana María; Martínez, María Adela; Leiva, Ana María; Alvarez, Cristian; Aguilar-Farías, Nicolás; Ramírez-Campillo, Rodrigo; Martínez, Ximena Díaz; Sanzana-Inzunza, Ruth; Celis-Morales, Carlos
2016-11-01
Sedentary behavior is a major risk factor for cardiovascular disease and mortality. To investigate whether the associations between sedentary behavior and cardiometabolic markers differs across physical activity levels. Cross sectional study of 314 participants aged 18 to 65 years. Body mass index (BMI) and waist circumference were measured, and body fat was derived from the sum of four skinfolds. Physical activity was measured objectively using accelerometers (Actigraph GT1M, USA®). A fasting blood sample was obtained to measure glucose, insulin, HOMA-IR, lipid profile and high sensitive C reactive protein (hsCRP). Those participants with an activity level > 600 MET.min-1.week-1 were classified as physically active. Thirty four percent of participants were physically inactive and spent an average of 8.7 h.day-1 in sedentary pursuits. Physically inactive individuals had poorer cardiometabolic health than their physically active counterparts. Per one hour decrease in overall sedentary behavior, there was a significant improvement in glucose (-8.46 and -4.68 mg.dl-1), insulin (-2.12 and -1.77 pmol.l-1), HOMA-IR (-0.81 and -0.56) BMI (-0.93 and -0.62 kg.m-2) and waist circumference (-2.32 and -1.65 cm) in physically active and inactive participants, respectively. Being physically active may modify the detrimental effects of sedentary behavior on cardiometabolic and obesity-related traits.
Dahl, Viktor; Lee, Evelyn; Peterson, Julia; Spudich, Serena S.; Leppla, Idris; Sinclair, Elizabeth; Fuchs, Dietmar; Palmer, Sarah
2011-01-01
Background. Despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA by antiretroviral therapy to levels below clinical assay detection, infection and immune activation may persist within the central nervous system and possibly lead to continued brain injury. We hypothesized that intensifying therapy would decrease cerebrospinal fluid (CSF) infection and immune activation. Methods. This was a 12-week, randomized, open-label pilot study comparing addition of the integrase inhibitor raltegravir to no treatment augmentation, with an option for rollover to raltegravir. CSF and plasma were analyzed for HIV-1 RNA using a single-copy assay. CSF and blood immune activation was assessed by neopterin concentrations and CD4+ and CD8+ T-cell surface antigen expression. Results. Primary analysis compared 14 intensified (including rollovers) to 9 nonintensified subject experiences. Median HIV-1 RNA levels in all samples were lower in CSF (<.3 copies/mL) than in plasma (<.9 copies/mL; P < .0001), and raltegravir did not reduce HIV-1 RNA, CSF neopterin, or CD4+ and CD8+ T-cell activation. Conclusions. Raltegravir intensification did not reduce intrathecal immunoactivation or alter CSF HIV-1 RNA levels in subjects with baseline viral suppression. With and without raltegravir intensification, HIV RNA levels in CSF were very low in the enrolled subjects. Clinical Trials Registration. NCT00672932. PMID:22021620
Kothur, Kavitha; Wienholt, Louise; Mohammad, Shekeeb S.; Tantsis, Esther M.; Pillai, Sekhar; Britton, Philip N.; Jones, Cheryl A.; Angiti, Rajeshwar R.; Barnes, Elizabeth H.; Schlub, Timothy; Bandodkar, Sushil; Brilot, Fabienne; Dale, Russell C.
2016-01-01
Background Despite the discovery of CSF and serum diagnostic autoantibodies in autoimmune encephalitis, there are still very limited CSF biomarkers for diagnostic and monitoring purposes in children with inflammatory or autoimmune brain disease. The cause of encephalitis is unknown in up to a third of encephalitis cohorts, and it is important to differentiate infective from autoimmune encephalitis given the therapeutic implications. Aim To study CSF cytokines and chemokines as diagnostic biomarkers of active neuroinflammation, and assess their role in differentiating demyelinating, autoimmune, and viral encephalitis. Methods We measured and compared 32 cytokine/chemokines using multiplex immunoassay and APRIL and BAFF using ELISA in CSF collected prior to commencing treatment from paediatric patients with confirmed acute disseminated encephalomyelitis (ADEM, n = 16), anti-NMDAR encephalitis (anti-NMDAR E, n = 11), and enteroviral encephalitis (EVE, n = 16). We generated normative data using CSF from 20 non-inflammatory neurological controls. The sensitivity of CSF cytokine/chemokines to diagnose encephalitis cases was calculated using 95th centile of control values as cut off. We correlated CSF cytokine/chemokines with disease severity and follow up outcome based on modified Rankin scale. One-way hierarchical correlational cluster analysis of molecules was performed in different encephalitis and outcome groups. Results In descending order, CSF TNF-α, IL-10, IFN-α, IL-6, CXCL13 and CXCL10 had the best sensitivity (>79.1%) when all encephalitis patients were included. The combination of IL-6 and IFN-α was most predictive of inflammation on multiple logistic regression with area under the ROC curve 0.99 (CI 0.97–1.00). There were no differences in CSF cytokine concentrations between EVE and anti-NMDAR E, whereas ADEM showed more pronounced elevation of Th17 related (IL-17, IL-21) and Th2 (IL-4, CCL17) related cytokine/chemokines. Unlike EVE, heat map analysis
Wiewelhove, Thimo; Raeder, Christian; Meyer, Tim; Kellmann, Michael; Pfeiffer, Mark; Ferrauti, Alexander
2016-11-01
To investigate the effect of repeated use of active recovery during a 4-d shock microcycle with 7 high-intensity interval-training (HIT) sessions on markers of fatigue. Eight elite male junior tennis players (age 15.1 ± 1.4 y) with an international ranking between 59 and 907 (International Tennis Federation) participated in this study. After each training session, they completed 15 min of either moderate jogging (active recovery [ACT]) or passive recovery (PAS) with a crossover design, which was interrupted by a 4-mo washout period. Countermovement-jump (CMJ) height, serum concentration of creatine kinase (CK), delayed-onset muscle soreness (DOMS), and perceived recovery and stress (Short Recovery and Stress Scale) were measured 24 h before and 24 h after the training program. The HIT shock microcycle induced a large decrease in CMJ performance (ACT: effect size [ES] = -1.39, P < .05; PAS: ES = -1.42, P < .05) and perceived recovery (ACT: ES = -1.79, P < .05; PAS: ES = -2.39, P < .05), as well as a moderate to large increase in CK levels (ACT: ES = 0.76, P > .05; PAS: ES = 0.81, P >.05), DOMS (ACT: ES = 2.02, P < .05; PAS: ES = 2.17, P < .05), and perceived stress (ACT: ES = 1.98, P < .05; PAS: ES = 3.06, P < .05), compared with the values before the intervention. However, no significant recovery intervention × time interactions or meaningful differences in changes were noted in any of the markers between ACT and PAS. Repeated use of individualized ACT, consisting of 15 min of moderate jogging, after finishing each training session during an HIT shock microcycle did not affect exercise-induced fatigue.
Engels, Eric A.; Savoldo, Barbara; Pfeiffer, Ruth M.; Costello, Rene; Zingone, Adriana; Heslop, Helen E.; Landgren, Ola
2012-01-01
Introduction Transplant recipients are at risk of post-transplant lymphoproliferative disease (PTLD). Methods: Thirty-six pediatric transplant recipients were evaluated (18 hematopoietic stem cell and 18 liver recipients; 12 had PTLD). We studied 207 longitudinal plasma samples from these recipients for three markers of B-cell activation or clonality: immunoglobulin free light chains (FLCs), soluble CD30 (sCD30), and monoclonal immunoglobulins (M-proteins). Results Kappa FLCs, lambda FLCs, and sCD30 were elevated in 20.8%, 28.0%, and 94.2% of plasma specimens, respectively. FLC and sCD30 levels increased significantly 1.18–1.82 fold per log10 Epstein Barr virus (EBV) load in peripheral blood. Five PTLD cases manifested elevated FLCs with an abnormal kappa/lambda ratio, suggesting monoclonal FLC production. M-proteins were present in 91% of PTLD cases, vs. 50–67% of other recipients with high or low EBV loads (p=0.13). Concordance of FLCs, M-proteins, and PTLD tumor light chain restriction was imperfect. For example, one PTLD case with an IgG lambda M-protein had a tumor that was kappa restricted, and another case with an M-protein had a T-cell PTLD. In an additional case, an IgM kappa M-protein and excess kappa FLCs were both detected in plasma at PTLD diagnosis; while the tumor was not restricted at diagnosis, kappa restriction was present 5 years later when the PTLD relapsed. Discussion Plasma markers of B-cell dysfunction are frequent following transplantation and associated with poor EBV control. These abnormal markers may be produced by oligoclonal B-cell populations or PTLD tumor cells, and could potentially help identify recipients at high risk of PTLD. PMID:23222884
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.
Background: Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation. Methods: A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991–1994. Plasma suPAR was assessed bymore » ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded. Results: After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p<0.001). In never-smokers, a 3-fold increase in blood cadmium was associated with a 3.7% increase in suPAR concentration (p<0.01) after full adjustment. Blood cadmium was not associated with C-reactive protein, white blood cell count and Lp-PLA2 but with neutrophil/lymphocyte ratio in one of two statistical models. Conclusions: Exposure to cadmium was associated with increased plasma suPAR in the general population, independently of smoking and cardiovascular disease. These results imply that cadmium is a possible cause for raised levels of this inflammatory marker. - Highlights: • Cadmium is a toxic proinflammatory, proatherosclerotic metal. • Soluble urokinase-type plasminogen activator receptor (suPAR) in plasma is a promising proinflammatory marker of atherosclerosis. • Blood cadmium and
... such as stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) , or proton therapy . Fiducial markers are small ... Proton Therapy Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotherapy (SBRT) Images related to Fiducial Marker Placement Sponsored ...
Prigge, Vanessa; Melchinger, Albrecht E; Dhillon, Baldev S; Frisch, Matthias
2009-06-01
Expenses for marker assays are the major costs in marker-assisted backcrossing programs for the transfer of target genes from a donor into the genetic background of a recipient genotype. Our objectives were to (1) investigate the effect of employing sequentially increasing marker densities over backcross generations on the recurrent parent genome (RPG) recovery and the number of marker data points (MDP) required, and (2) determine optimum designs for attaining RPG thresholds of 93-98% with a minimum number of MDP. We simulated the introgression of one dominant target gene for genome models of sugar beet (Beta vulgaris L.) and maize (Zea mays L.) with varying marker distances of 5-80 cM and population sizes of 30-250 plants across BC(1) to BC(3) generations. Employing less dense maps in early backcross generations resulted in savings of over 50% in the number of required MDP compared with using a constant set of markers and was accompanied only by small reductions in the attained RPG values. The optimum designs were characterized by increasing marker densities and increasing population sizes in advanced generations for both genome models. We conclude that increasing simultaneously the marker density and the population size from early to advanced backcross generations results in gene introgression with a minimum number of required MDP.
Cancer risk associated with chronic diseases and disease markers: prospective cohort study.
Tu, Huakang; Wen, Chi Pang; Tsai, Shan Pou; Chow, Wong-Ho; Wen, Christopher; Ye, Yuanqing; Zhao, Hua; Tsai, Min Kuang; Huang, Maosheng; Dinney, Colin P; Tsao, Chwen Keng; Wu, Xifeng
2018-01-31
To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers. Prospective cohort study. Standard medical screening program in Taiwan. 405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years. Cancer incidence and cancer mortality. A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among physically active (versus inactive) participants, the increased cancer risk
Criteria for selection and application of molecular markers for clinical studies of osteoarthritis.
Otterness, I G; Swindell, A C
2003-03-01
To develop criteria for the selection and application of molecular markers for the study of osteoarthritis (OA). Statistical criteria for marker selection for OA are developed. After studying more than 20 different molecular markers for monitoring OA, procedures for choosing markers for clinical studies have been developed. For a particular study, the process starts with the markers showing 'face-validity' for monitoring OA. They are next required to successfully distinguish OA patients from controls. This necessitates definition of the distribution of marker values in OA patients and controls. So far, they have been consistently log-normal. The difference (Delta) in marker values between OA and controls defines the opportunity for marker improvement. The between-visit standard deviation (S) in patients puts limits on the detection of marker changes. The two variables can be combined to estimate the practicality of a marker using a modified power analysis. The number of patients (N*) required to observe a 50% improvement with an alpha level of P=0.05 and with 80% certainty is estimated as 50(S/Delta)(2). N*, S and Delta should be used to characterize and compare markers. Marker efficiency can be refined by regressing on secondary variables, such as age, sex, BMI, severity, etc. Finally, the use of two or more markers may be required to improve marker prediction of clinical outcome. Correlated markers can be used to reinforce conclusions by essentially adding replicative data. Independent, complementary markers can be used to develop associations with clinical parameters, and perhaps diagnose and monitor disease status, activities that so far have not been possible with single markers.
Marker vaccine strategies and candidate CSFV marker vaccines.
Dong, Xiao-Nan; Chen, Ying-Hua
2007-01-04
Classical swine fever (CSF) is an economically important highly contagious disease of swine worldwide. Classical swine fever virus (CSFV) is its etiological agent, and the only natural hosts are domestic pigs and wild boars. Although field CSFV strains vary in the virulence, they all result in serious losses in pig industry. Highly virulent field strains generally cause acute disease and high mortality; moderately virulent field strains raise subacute or chronic infections; postnatal infection by low virulent field strains produces subclinical infection and mortality in the new-born piglets. CSFV can cross the placental barrier, and this transplacental transmission usually results in mortality of fetuses and birth of congenitally infected pigs with a late-onset disease and death. Two main strategies to control CSF epidemic are systematic prophylactic vaccination with live attenuated vaccines (such as C-strain) and non-vaccination stamping-out policy. But neither of them is satisfying enough. Marker vaccine and companion serological diagnostic test is thought to be a promising strategy for future control and eradication of CSF. During the past 15 years, various candidate marker vaccines were constructed and evaluated in the animal experiments, including recombinant chimeric vaccines, recombinant deletion vaccines, DNA vaccines, subunit vaccines and peptide vaccines. Among them, two subunit vaccines entered the large scale marker vaccine trial of EU in 1999. Although they failed to fulfil all the demands of the Scientific Veterinary Committee, they successfully induced solid immunity against CSFV in the vaccinated pigs. It can be expected that new potent marker vaccines might be commercially available and used in systematic prophylactic vaccination campaign or emergency vaccination in the next 15 years. Here, we summarized current strategies and candidate CSFV marker vaccines. These strategies and methods are also helpful for the development of new
Enzyme markers in inbred rat strains: genetics of new markers and strain profiles.
Adams, M; Baverstock, P R; Watts, C H; Gutman, G A
1984-08-01
Twenty-six inbred strains of the laboratory rat (Rattus norvegicus) were examined for electrophoretic variation at an estimated 97 genetic loci. In addition to previously documented markers, variation was observed for the enzymes aconitase, aldehyde dehydrogenase, and alkaline phosphatase. The genetic basis of these markers (Acon-1, Ahd-2, and Akp-1) was confirmed. Linkage analysis between 35 pairwise comparisons revealed that the markers Fh-1 and Pep-3 are linked. The strain profiles of the 25 inbred strains at 11 electrophoretic markers are given.
Jones, Simon P; Franco, Nunzio F; Varney, Bianca; Sundaram, Gayathri; Brown, David A; de Bie, Josien; Lim, Chai K; Guillemin, Gilles J; Brew, Bruce J
2015-01-01
The kynurenine pathway is a fundamental mechanism of immunosuppression and peripheral tolerance. It is increasingly recognized as playing a major role in the pathogenesis of a wide variety of inflammatory, neurodegenerative and malignant disorders. However, the temporal dynamics of kynurenine pathway activation and metabolite production in human immune cells is currently unknown. Here we report the novel use of flow cytometry, combined with ultra high-performance liquid chromatography and gas chromatography-mass spectrometry, to sensitively quantify the intracellular expression of three key kynurenine pathway enzymes and the main kynurenine pathway metabolites in a time-course study. This is the first study to show that up-regulation of indoleamine 2,3-dioxygenase (IDO-1), kynurenine 3-monoxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) is lacking in lymphocytes treated with interferon gamma. In contrast, peripheral monocytes showed a significant elevation of kynurenine pathway enzymes and metabolites when treated with interferon gamma. Expression of IDO-1, KMO and QPRT correlated significantly with activation of the kynurenine pathway (kynurenine:tryptophan ratio), quinolinic acid concentration and production of the monocyte derived, pro-inflammatory immune response marker: neopterin. Our results also describe an original and sensitive methodological approach to quantify kynurenine pathway enzyme expression in cells. This has revealed further insights into the potential role of these enzymes in disease processes.
Anstey, K J; Smith, G A
1999-12-01
In this study a structural equation model of predictors of age differences in cognitive performance in late adulthood was developed. Biological markers of aging (vision, hearing, vibration sense, forced expiratory volume, and grip strength) were used as indicators of a latent variable called BioAge. A sample of 180 community-dwelling women aged 60 to 90 years was assessed. Results showed that BioAge explained all of the age-related variance in cognitive test performance. Physical health and physical activity had direct effects on BioAge. Measures of acculturation explained non-age-related variance in cognitive test performance. Some variables used as biomarkers also explained individual differences in measures of crystallized intelligence and perceptual speed. It is concluded that the association between biomarkers and cognition in old age is due to more than a common statistical association with age.
Engineering more stable, selectable marker-free autoluminescent mycobacteria by one step.
Yang, Feng; Njire, Moses M; Liu, Jia; Wu, Tian; Wang, Bangxing; Liu, Tianzhou; Cao, Yuanyuan; Liu, Zhiyong; Wan, Junting; Tu, Zhengchao; Tan, Yaoju; Tan, Shouyong; Zhang, Tianyu
2015-01-01
In our previous study, we demonstrated that the use of the autoluminescent Mycobacterium tuberculosis as a reporter strain had the potential to drastically reduce the time, effort, animals and costs consumed in evaluation of the activities of drugs and vaccines in live mice. However, the strains were relatively unstable and lost reporter with time without selection. The kanamycin selection marker used wasn't the best choice as it provides resistance to amino glycosides which are an important class of second line drugs used in tuberculosis treatment. In addition, the marker could limit utility of the strains for screening of new potential drugs or evaluating drug combinations for tuberculosis treatment. Limited selection marker genes for mycobacterial genetic manipulation is a major drawback for such a marker-containing strain in many research fields. Therefore, selectable marker-free, more stable autoluminescent mycobacteria are highly needed. After trying several strategies, we created such mycobacterial strains successfully by using an integrative vector and removing both the resistance maker and integrase genes by Xer site-specific recombination in one step. The corresponding plasmid vectors developed in this study could be very convenient in constructing other selectable marker-free, more stable reporter mycobacteria with diverse applications.
Marker Registration Technique for Handwritten Text Marker in Augmented Reality Applications
NASA Astrophysics Data System (ADS)
Thanaborvornwiwat, N.; Patanukhom, K.
2018-04-01
Marker registration is a fundamental process to estimate camera poses in marker-based Augmented Reality (AR) systems. We developed AR system that creates correspondence virtual objects on handwritten text markers. This paper presents a new method for registration that is robust for low-content text markers, variation of camera poses, and variation of handwritten styles. The proposed method uses Maximally Stable Extremal Regions (MSER) and polygon simplification for a feature point extraction. The experiment shows that we need to extract only five feature points per image which can provide the best registration results. An exhaustive search is used to find the best matching pattern of the feature points in two images. We also compared performance of the proposed method to some existing registration methods and found that the proposed method can provide better accuracy and time efficiency.
Yeh, Lee-Chuan C; Ma, Xiuye; Ford, Jeffery J; Adamo, Martin L; Lee, John C
2013-08-01
Bone morphogenetic proteins (BMPs) promote osteoblast differentiation and bone formation in vitro and in vivo. BMPs canonically signal through Smad transcription factors, but BMPs may activate signaling pathways traditionally stimulated by growth factor tyrosine kinase receptors. Of these, the mTOR pathway has received considerable attention because BMPs activate P70S6K, a downstream effector of mTOR, suggesting that BMP-induced osteogenesis is mediated by mTOR activation. However, contradictory effects of the mTOR inhibitor rapamycin (RAPA) on bone formation have been reported. Since bone formation is thought to be inversely related to lipid accumulation and mTOR is also important for lipid synthesis, we postulated that BMP-7 may stimulate lipogenic enzyme expression in a RAPA-sensitive mechanism. To test this hypothesis, we determined the effects of RAPA on BMP-7-stimulated expression of osteogenic and lipogenic markers in cultured fetal rat calvarial cells. Our study showed that BMP-7 promoted the expression of osteogenic and lipogenic markers. The effect of BMP-7 on osteogenic markers was greater in magnitude than on lipogenic markers and was temporally more sustained. RAPA inhibited basal and BMP-7-stimulated osteogenic and lipogenic marker expression and bone nodule mineralization. The acetyl CoA carboxylase inhibitor TOFA stimulated the expression of osteoblast differentiation markers, whereas palmitate suppressed their expression. We speculate that the BMP-7-stimulated adipogenesis is part of the normal anabolic response to BMPs, but that inappropriate activation of the lipid biosynthetic pathway by mTOR could have deleterious effects on bone formation and could explain paradoxical effects of RAPA to promote bone formation. Copyright © 2013 Wiley Periodicals, Inc.
Pelevina, I I; Aleshchenko, A V; Antoshchina, M M; Kudriashova, O M; Nikonova, M F; Riabchenko, N I; Serebrianyĭ, A M; Iarilin, A A
2013-01-01
Expression of activation (CD69) and proliferation (Ki67) markers, their connection with each other, with the oxidative status (reactive oxygen species--ROS) and with radiosensitivity (determined by micronucleus test) have been studied on stimulated blood lymphocytes from Moscow inhabitants. It was shown that the content of T-lymphocytes with the expressed CD69 and the content of T-lymphocytes with the expressed Ki67 markers correlate (r = 0.571; p = 0.0004). We can suppose that expression of the CD69 marker (24 h after PHA stimulation) is needed for the cell cycle progression, but it is not enough for the high expression of Ki67 markers 48 h after stimulation (DNA synthesis phase). It was discovered that T-lymphocytes with the CD69 marker or T-lymphocytes with the Ki67 marker are connected by the negative correlation with the frequency of irradiated cell with micronucleus (MN) r = -0.487; p = 0.010; r = -0.440; p = 0.008, respectively. So we can suppose that lymphocyte radiosensitivity decreased with the increase of expression activation and proliferation markers. It was shown that radiosensitivity determined by MN test is not connected with the oxidative status determined by the reactive oxygen species content including superoxide anion radicals. It is possible to explain by the fact that the ROS concentration has been determined in non-stimulated lymphocytes, but frequencies of cells with MN - in the stimulated cells 48 h after stimulation. Using separate analysis of individual differences by the studied parameters that were determined in the same people, it was shown that individual differences are high enough in the same cases. For example, the radiosensitivity when cells were irradiated 48 h after stimulation, ROS concentration, cell content with activation and proliferation markers. In conclusion, we can say that we failed to find important correlation between the parameters studied. However, the presence of individual differences in the marker expression
Horvath, A; Leber, B; Schmerboeck, B; Tawdrous, M; Zettel, G; Hartl, A; Madl, T; Stryeck, S; Fuchs, D; Lemesch, S; Douschan, P; Krones, E; Spindelboeck, W; Durchschein, F; Rainer, F; Zollner, G; Stauber, R E; Fickert, P; Stiegler, P; Stadlbauer, V
2016-11-01
Probiotics may correct intestinal dysbiosis and proinflammatory conditions in patients with liver cirrhosis. To test the effects of a multispecies probiotic on innate immune function, bacterial translocation and gut permeability. In a randomised, double blind, placebo-controlled study, stable cirrhotic out-patients either received a daily dose of a probiotic powder containing eight different bacterial strains (Ecologic Barrier, Winclove, Amsterdam, The Netherlands) (n = 44) or a placebo (n = 36) for 6 months and were followed up for another 6 months. We found a significant but subclinical increase in neutrophil resting burst (2.6-3.2%, P = 0.0134) and neopterin levels (7.7-8.4 nmol/L, P = 0.001) with probiotics but not with placebo. Probiotic supplementation did not have a significant influence on neutrophil phagocytosis, endotoxin load, gut permeability or inflammatory markers. Ten severe infections occurred in total; one during intervention in the placebo group, and five and four after the intervention has ended in the probiotic and placebo group, respectively. Liver function showed some improvement with probiotics but not with placebo. Probiotic supplementation significantly increased serum neopterin levels and the production of reactive oxygen species by neutrophils. These findings might explain the beneficial effects of probiotics on immune function. Furthermore, probiotic supplementation may be a well-tolerated method to maintain or even improve liver function in stable cirrhosis. However, its influence on gut barrier function and bacterial translocation in cirrhotic patients is minimal. © 2016 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.
Zhuo, Limeng; Peng, Jingjing; Zhao, Yunli; Li, Dongxiang; Xie, Xiuman; Tong, Ling; Yu, Zhiguo
2017-10-01
Traditional Chinese medicine consists of complex phytochemical constituents. Selecting appropriate analytical markers of traditional Chinese medicine is a critical step in quality control. Currently, the combination of fingerprinting and efficacy evaluation is considered as a useful method for screening active ingredients in complex mixtures. This study was designed to develop an orthogonal partial least squares model for screening bioactive quality control markers of QishenYiqi dripping pills based on the fingerprint-efficacy relationship. First, the chemical fingerprints of 49 batches of QishenYiqi dripping pill samples were established by ultra-high performance liquid chromatography coupled with a photodiode array detector. Second, ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was exploited to systematically investigate the 36 copossessing fingerprint components in QishenYiqi dripping pills. The vascular protective activity of QishenYiqi dripping pills was determined by using a cell counting kit-8 assay. Finally, fingerprint-efficacy relationship was established by orthogonal partial least squares model. The results indicated that ten components exhibited strong correlation with vascular protective activity, and these were preliminarily screened as quality control markers. The present study provided a novel idea for the study of the pharmacodynamic material basis and quality evaluation of QishenYiqi dripping pills. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Farcet, Anaïs; de Decker, Laure; Pauly, Vanessa; Rousseau, Frédérique; Bergman, Howard; Molines, Catherine; Retornaz, Frédérique
2016-01-01
Comprehensive Geriatric Assessment (CGA) is the gold standard to help oncologists select the best cancer treatment for their older patients. Some authors have suggested that the concept of frailty could be a more useful approach in this population. We investigated whether frailty markers are associated with treatment recommendations in an oncogeriatric clinic. This prospective study included 70 years and older patients with solid tumors and referred for an oncogeriatric assessment. The CGA included nine domains: autonomy, comorbidities, medication, cognition, nutrition, mood, neurosensory deficits, falls, and social status. Five frailty markers were assessed (nutrition, physical activity, energy, mobility, and strength). Patients were categorized as Frail (three or more frailty markers), pre-frail (one or two frailty markers), or not-frail (no frailty marker). Treatment recommendations were classified into two categories: standard treatment with and without any changes and supportive/palliative care. Multiple logistic regression models were used to analyze factors associated with treatment recommendations. 217 patients, mean age 83 years (± Standard deviation (SD) 5.3), were included. In the univariate analysis, number of frailty markers, grip strength, physical activity, mobility, nutrition, energy, autonomy, depression, Eastern Cooperative Oncology Group Scale of Performance Status (ECOG-PS), and falls were significantly associated with final treatment recommendations. In the multivariate analysis, the number of frailty markers and basic Activities of Daily Living (ADL) were significantly associated with final treatment recommendations (p<0.001 and p = 0.010, respectively). Frailty markers are associated with final treatment recommendations in older cancer patients. Longitudinal studies are warranted to better determine their use in a geriatric oncology setting.
Huang, Yuanshen; Wang, Yang; Yu, Jie; Gao, Min; Levings, Megan; Wei, Shencai; Zhang, Shengquan; Xu, Aie; Su, Mingwan; Dutz, Jan; Zhang, Xuejun; Zhou, Youwen
2012-01-01
Background Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients. Methods and Materials Paired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy. Results Compared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients. Conclusions and Clinical Implications As the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting
Cirelli, Kimberly M.; Dan, Jennifer M.; Morou, Antigoni; Daigneault, Audrey; Brassard, Nathalie; Silvestri, Guido; Routy, Jean-Pierre; Havenar-Daughton, Colin; Crotty, Shane
2017-01-01
The identification and study of antigen-specific CD4 T cells, both in peripheral blood and in tissues, is key for a broad range of immunological research, including vaccine responses and infectious diseases. Detection of these cells is hampered by both their rarity and their heterogeneity, in particular with regards to cytokine secretion profiles. These factors prevent the identification of the total pool of antigen-specific CD4 T cells by classical methods. We have developed assays for the highly sensitive detection of such cells by measuring the upregulation of surface activation induced markers (AIM). Here, we compare two such assays based on concurrent expression of CD69 plus CD40L (CD154) or expression of OX40 plus CD25, and we develop additional AIM assays based on OX40 plus PD-L1 or 4-1BB. We compare the relative sensitivity of these assays for detection of vaccine and natural infection-induced CD4 T cell responses and show that these assays identify distinct, but overlapping populations of antigen-specific CD4 T cells, a subpopulation of which can also be detected on the basis of cytokine synthesis. Bystander activation had minimal effect on AIM markers. However, some T regulatory cells upregulate CD25 upon antigen stimulation. We therefore validated AIM assays designed to exclude most T regulatory cells, for both human and non-human primate (NHP, Macaca mulatta) studies. Overall, through head-to-head comparisons and methodological improvements, we show that AIM assays represent a sensitive and valuable method for the detection of antigen-specific CD4 T cells. PMID:29065175
Reiss, Samantha; Baxter, Amy E; Cirelli, Kimberly M; Dan, Jennifer M; Morou, Antigoni; Daigneault, Audrey; Brassard, Nathalie; Silvestri, Guido; Routy, Jean-Pierre; Havenar-Daughton, Colin; Crotty, Shane; Kaufmann, Daniel E
2017-01-01
The identification and study of antigen-specific CD4 T cells, both in peripheral blood and in tissues, is key for a broad range of immunological research, including vaccine responses and infectious diseases. Detection of these cells is hampered by both their rarity and their heterogeneity, in particular with regards to cytokine secretion profiles. These factors prevent the identification of the total pool of antigen-specific CD4 T cells by classical methods. We have developed assays for the highly sensitive detection of such cells by measuring the upregulation of surface activation induced markers (AIM). Here, we compare two such assays based on concurrent expression of CD69 plus CD40L (CD154) or expression of OX40 plus CD25, and we develop additional AIM assays based on OX40 plus PD-L1 or 4-1BB. We compare the relative sensitivity of these assays for detection of vaccine and natural infection-induced CD4 T cell responses and show that these assays identify distinct, but overlapping populations of antigen-specific CD4 T cells, a subpopulation of which can also be detected on the basis of cytokine synthesis. Bystander activation had minimal effect on AIM markers. However, some T regulatory cells upregulate CD25 upon antigen stimulation. We therefore validated AIM assays designed to exclude most T regulatory cells, for both human and non-human primate (NHP, Macaca mulatta) studies. Overall, through head-to-head comparisons and methodological improvements, we show that AIM assays represent a sensitive and valuable method for the detection of antigen-specific CD4 T cells.
Halldén, G; Nopp, A; Ihre, E; Peterson, C; Lundahl, J
1999-11-01
Serum-ECP, EG2-epitope on intracellular ECP and surface expression of CD9 and CD11b in peripheral blood eosinophils (PBE) are considered to be markers that mirror clinical parameters in allergic inflammation. The aim was to investigate the impact of the blood sampling procedure on PBE markers and to identify optimal conditions for extended pre-analysis storage. Blood, from healthy individuals and patients with allergic rhinitis/asthma, was collected in tubes with EDTA, citrate, or without anti-coagulant. The expression of EG2-epitope, CD9, and CD11b were analyzed in eosinophils and neutrophils after 1, 5, and 24 hours of storage at +4 degrees C, according to the FOG-method and flow cytometry. In vitro stimulation with fMLP/PMA was used for metabolic activity analysis and CD11b mobilization. Following a 1-hour clotting period at +20 to 22 degrees C, samples were stored at +4 degrees C and serum-ECP levels were measured. The EG2-epitope, serum-ECP, and CD9 were stable in samples from both healthy controls and allergic patients at all storage conditions. The EG2-epitope, serum-ECP and PBE count were significantly increased in the patient group, whereas no differences were observed in the expression of CD9 or CD11b. Both granulocytes and monocytes retained their metabolic activity for 24 hours. Neutrophils in citrate-blood increased their ability to respond to fMLP, as compared with EDTA-blood. In vitro analysis of selected activity markers and functional tests could be performed on granulocytes from both healthy individuals and allergic patients after 24 hours storage at +4 degrees C. The anticoagulant citrate seems to be preferable to EDTA when monocytes or CD11b expression are analyzed.
Inflamm-aging does not simply reflect increases in pro-inflammatory markers.
Morrisette-Thomas, Vincent; Cohen, Alan A; Fülöp, Tamàs; Riesco, Éléonor; Legault, Véronique; Li, Qing; Milot, Emmanuel; Dusseault-Bélanger, Françis; Ferrucci, Luigi
2014-07-01
Many biodemographic studies use biomarkers of inflammation to understand or predict chronic disease and aging. Inflamm-aging, i.e. chronic low-grade inflammation during aging, is commonly characterized by pro-inflammatory biomarkers. However, most studies use just one marker at a time, sometimes leading to conflicting results due to complex interactions among the markers. A multidimensional approach allows a more robust interpretation of the various relationships between the markers. We applied principal component analysis (PCA) to 19 inflammatory biomarkers from the InCHIANTI study. We identified a clear, stable structure among the markers, with the first axis explaining inflammatory activation (both pro- and anti-inflammatory markers loaded strongly and positively) and the second axis innate immune response. The first but not the second axis was strongly correlated with age (r=0.56, p<0.0001, r=0.08 p=0.053), and both were strongly predictive of mortality (hazard ratios per PCA unit (95% CI): 1.33 (1.16-1.53) and 0.87 (0.76-0.98) respectively) and multiple chronic diseases, but in opposite directions. Both axes were more predictive than any individual markers for baseline chronic diseases and mortality. These results show that PCA can uncover a novel biological structure in the relationships among inflammatory markers, and that key axes of this structure play important roles in chronic disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Jenny, M; Santer, E; Klein, A; Ledochowski, M; Schennach, H; Ueberall, F; Fuchs, D
2009-03-18
The fruits of Theobroma cacao L. (Sterculiaceae) have been used as food and a remedy for more than 4000 years. Today, about 100 therapeutic applications of cacao are described involving the gastrointestinal, nervous, cardiovascular and immune systems. Pro-inflammatory cytokine interferon-gamma and related biochemical pathways like tryptophan degradation by indoleamine 2,3-dioxygenase and neopterin formation are closely associated with the pathogenesis of such disorders. To determine the anti-inflammatory effect of cacao extracts on interferon-gamma and biochemical consequences in immunocompetent cells. Effects of aqueous or ethanolic extracts of cacao were examined on mitogen-induced human peripheral blood mononuclear cells (PBMC) of healthy donors and on lipopolysaccharide-stimulated myelomonocytic THP-1 cells. Antioxidant activity of extracts was determined by oxygen radical absorption capacity (ORAC) assay. In mitogen-stimulated PBMC, enhanced degradation of tryptophan, formation of neopterin and interferon-gamma were almost completely suppressed by the cacao extracts at doses of > or = 5 microg/mL. Cacao extracts had no effect on tryptophan degradation in lipopolysaccharide-stimulated THP-1 cells. There is a significant suppressive effect of cacao extracts on pro-inflammatory pathways in activated T-cells. Particularly the influence on indoleamine 2,3-dioxygenase could relate to some of the beneficial health effects ascribed to cacao.
Monitoring of 30 marker candidates in early Parkinson disease as progression markers
Zimmermann, Johannes; Sixel-Döring, Friederike; Focke, Niels K.; Wicke, Tamara; Ebentheuer, Jens; Schaumburg, Martina; Lang, Elisabeth; Trautmann, Ellen; Zetterberg, Henrik; Taylor, Peggy; Friede, Tim; Trenkwalder, Claudia
2016-01-01
Objective: This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106). Methods: Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI). Results: A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09–0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06–0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24–0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25–0.64), and RBD by PSG (d 0.37; CI 0.19–0.55) as well as VBM units of cortical gray matter (d −0.2; CI −0.3 to −0.09) and hippocampus (d −0.15; CI −0.27 to −0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d −0.19; CI −0.36 to −0.02) and 2 depression scales (Beck Depression Inventory d −0.18; CI −0.36 to 0; Montgomery-Åsberg Depression Rating Scale d −0.26; CI −0.47 to −0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants. Conclusions: Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression. PMID:27164658
Monitoring of 30 marker candidates in early Parkinson disease as progression markers.
Mollenhauer, Brit; Zimmermann, Johannes; Sixel-Döring, Friederike; Focke, Niels K; Wicke, Tamara; Ebentheuer, Jens; Schaumburg, Martina; Lang, Elisabeth; Trautmann, Ellen; Zetterberg, Henrik; Taylor, Peggy; Friede, Tim; Trenkwalder, Claudia
2016-07-12
This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106). Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI). A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09-0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06-0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24-0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25-0.64), and RBD by PSG (d 0.37; CI 0.19-0.55) as well as VBM units of cortical gray matter (d -0.2; CI -0.3 to -0.09) and hippocampus (d -0.15; CI -0.27 to -0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d -0.19; CI -0.36 to -0.02) and 2 depression scales (Beck Depression Inventory d -0.18; CI -0.36 to 0; Montgomery-Åsberg Depression Rating Scale d -0.26; CI -0.47 to -0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants. Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression. © 2016 American Academy of Neurology.
He, Jun; Feng, Xinchi; Wang, Kai; Liu, Changxiao; Qiu, Feng
2018-02-28
Quality control of Chinese medicine (CM) is an effective measure to ensure the safety and efficacy of CM in clinical practice, which is also a key factor to restrict the modernization process of CM. Various chemical components exist in CM and the determination of several chemical components is the main approach for quality control of vast majority of CM in the present. However, many components determined lack not only specificity, but also biological activities. This is bound to greatly reduce the actual value of quality standard of CM. Professor Changxiao Liu proposed the "quality marker" (Q-marker) concept to ensure the standardization and rationalization for the quality control of CM. As we all know, CMs are taken orally in most cases and could be extensively metabolized in vivo. Both prototype components and the metabolites could be the actual therapeutic material basis. Pharmacokinetic studies could benefit the elucidation of actual therapeutic material basis which is closely related to the identification of Q-markers. Therefore, a new strategy about Q-marker was proposed based on the pharmacokinetic analysis of CM, hoping to provide some ideas for the discovery and identification of Q-marker. The relationship between pharmacokinetic studies and the identification of Q-markers was demonstrated in this review and a new strategy was proposed. Starting from the pharmacokinetic analysis, reverse tracing of the prototype active components and the potential prodrugs in CM were conducted first and the therapeutic material basis were identified as Q-markers. Then, modern analytical techniques and methods were applied to obtain comprehensive quality control for these constituents. Several CMs including gingko biloba, ginseng, Periplocae Cortex, Mori Cortex, Bupleuri Radix and Scutellariae Radix were listed as examples to clarify how the new strategy could be applied. Pharmacokinetic studies play an important role for the elucidation of therapeutic material basis of CM
Cardiac markers: from enzymes to proteins, diagnosis to prognosis, laboratory to bedside.
Wu, A H
1999-01-01
For many years, serologic markers have been used to assist cardiologists in the diagnosis and management of patients with cardiovascular diseases. The use of laboratory markers has evolved and kept pace with the field of cardiology itself. The early markers involved testing for total enzyme activity such as aspartate aminotransferase, lactate dehydrogenase and creatine kinase. Shortly thereafter, the World Health Organization included serial enzyme markers as part of the triad for diagnosis of acute myocardial infarction (AMI). It was soon recognized that isoenzymes such as for CK-MB and LD-1 provided more specific organ specificity. The need for reporting rapid results led to the development of totally automated isoenzyme assays, which have evolved from immunoinhibition (INH) techniques to mass assays. The current emphasis for cardiac markers is use of protein markers such as cardiac troponin T (cTnT) and I (cTnI). These markers are more sensitive and specific than isoenzyme markers and enable risk stratification for non-AMI patients with unstable angina: patients with high troponin have a higher risk for AMI and cardiac death within the immediate future (4 to 6 weeks). Prospective management of cardiac patients requires more rapid testing and reporting of results. Point-of-care testing platforms on whole blood are now available for emergency testing at bedside.
Oxidative stress markers in aqueous humor of patients with senile cataracts.
Sawada, Hideko; Fukuchi, Takeo; Abe, Haruki
2009-01-01
To investigate the levels of oxidative stress markers in human eyes with senile cataracts. We conducted a retrospective, case-controlled study of 57 patients with senile cataracts. To assess oxidative stress markers in the eye, we measured the enzymatic activities of superoxide dismutase (SOD) and catalase (CAT) as well as the total protein levels in aqueous humor. In aqueous humor, SOD and CAT activity levels were 0.133 +/- 0.020 and 1.223 +/- 0.081 U/ml, respectively; protein levels were 2.372 +/- 0.166 mg/ml (means +/- SEM). We observed a significant increase in SOD activity and the protein level in progressed nuclear cataracts. No significant age-associated difference in antioxidant enzyme levels was detected. Significant increases in the levels of SOD activity and total protein correlated with the severity of the cataract but not with patient age, suggesting that progressed cataract is associated with molecules leaking from the lens capsule.
Maes, Michael; Bosmans, Eugene; Kubera, Marta
2015-01-01
There is now evidence that specific subgroups of patients with Myalgic Encephalomyelitis / chronic fatigue syndrome (ME/CFS) suffer from a neuro-psychiatric-immune disorder. This study was carried out to delineate the expression of the activation markers CD38 and human leukocyte antigen (HLA) DR on CD4+ and CD8+ peripheral blood lymphocytes in ME/CFS. Proportions and absolute numbers of peripheral lymphocytes expressing CD3+, CD19+, CD4+, CD8+, CD38+ and HLA-DR+ were measured in ME/CFS (n=139), chronic fatigue (CF, n=65) and normal controls (n=40). The proportions of CD3+, CD8+, CD8+CD38+ and CD8+HLA-DR+ were significantly higher in ME/CFS patients than controls, while CD38+, CD8+CD38+, CD8+HLA-DR+ and CD38+HLA-DR+ were significantly higher in ME/CFS than CF. The percentage of CD19+ cells and the CD4+/CD8+ ratio were significantly lower in ME/CFS and CF than in controls. There were highly significant inverse correlations between the increased expression of CD38+, especially that of CD8+CD38+, and the lowered CD4+/CD8+ ratio and CD19+ expression. There were no significant associations between the flow cytometric results and severity or duration of illness and peripheral blood biomarkers of oxidative and nitrosative stress (O&NS, i.e. IgM responses to O&N modified epitopes), leaky gut (IgM or IgA responses to LPS of gut commensal bacteria), cytokines (interleukin-1, tumor necrosis factor-α), neopterin, lysozyme and autoimmune responses to serotonin. The results support that a) increased CD38 and HLA-DR expression on CD8+ T cells are biomarkers of ME/CFS; b) increased CD38 antigen expression may contribute to suppression of the CD4+/CD8+ ratio and CD19+ expression; c) there are different immune subgroups of ME/CFS patients, e.g. increased CD8+ activation marker expression versus inflammation or O&NS processes; and d) viral infections or reactivation may play a role in a some ME/CFS patients.
Pyostomatitis vegetans. Clinical marker of ulcerative colitis.
Lopez-Jornet, P; Gomez-Garcia, F; Camacho-Alonso, F
2012-03-01
Pyodermatitis-pyostomatitis vegetans (PV), a rare disorder of the skin and oral mucosa, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis. We have presented the case of a patient with PV. This report emphasizes the relationship of PV to inflammatory bowel disease and the importance of the oral lesions as initial presenting signs of systemic disease or activity.
Marker Configuration Model-Based Roentgen Fluoroscopic Analysis.
Garling, Eric H; Kaptein, Bart L; Geleijns, Koos; Nelissen, Rob G H H; Valstar, Edward R
2005-04-01
It remains unknown if and how the polyethylene bearing in mobile bearing knees moves during dynamic activities with respect to the tibial base plate. Marker Configuration Model-Based Roentgen Fluoroscopic Analysis (MCM-based RFA) uses a marker configuration model of inserted tantalum markers in order to accurately estimate the pose of an implant or bone using single plane Roentgen images or fluoroscopic images. The goal of this study is to assess the accuracy of (MCM-Based RFA) in a standard fluoroscopic set-up using phantom experiments and to determine the error propagation with computer simulations. The experimental set-up of the phantom study was calibrated using a calibration box equipped with 600 tantalum markers, which corrected for image distortion and determined the focus position. In the computer simulation study the influence of image distortion, MC-model accuracy, focus position, the relative distance between MC-models and MC-model configuration on the accuracy of MCM-Based RFA were assessed. The phantom study established that the in-plane accuracy of MCM-Based RFA is 0.1 mm and the out-of-plane accuracy is 0.9 mm. The rotational accuracy is 0.1 degrees. A ninth-order polynomial model was used to correct for image distortion. Marker-Based RFA was estimated to have, in a worst case scenario, an in vivo translational accuracy of 0.14 mm (x-axis), 0.17 mm (y-axis), 1.9 mm (z-axis), respectively, and a rotational accuracy of 0.3 degrees. When using fluoroscopy to study kinematics, image distortion and the accuracy of models are important factors, which influence the accuracy of the measurements. MCM-Based RFA has the potential to be an accurate, clinically useful tool for studying kinematics after total joint replacement using standard equipment.
Lee, Kelly A; Goetting, Valerie S; Tell, Lisa A
2015-10-01
Changes in inflammatory marker concentrations or activity can be used to monitor health and disease condition of domestic animals but have not been applied with the same frequency to wildlife. We measured concentrations or activity of six inflammatory markers (ceruloplasmin, haptoglobin, mannan-binding lectin-dependent complement [MBL/complement], unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC), and plasma iron) in apparently healthy and sick or injured Red-tailed Hawks (Buteo jamaicensis). Haptoglobin and ceruloplasmin activities were consistently elevated in sick or injured hawks (2.1 and 2.5 times higher, respectively), and plasma iron concentrations decreased (0.46 times lower), relative to those of healthy birds. There were no differences between healthy and unhealthy hawks in TIBC and UIBC concentrations or MBL/complement activity. Therefore, haptoglobin, ceruloplasmin, and plasma iron would be useful inclusions in a panel of inflammatory markers for monitoring health in raptors.
Hassan, Sobia; Syed, Serajuddaula; Kehar, Shahnaz Imdad
2014-01-01
Objective: This study aims to determine expression of Glial Fibrillary Acidic Protein and of Alpha Smooth Muscle Actin (α-SMA) in hepatic stellate cells of CHC cases and their association with stage of fibrosis. Methods: The study was conducted at Ziauddin University, Clifton Campus during the year 2010-2012. Sixty Chronic Hepatitis C cases were immmunostained using anti α-SMA antibody and anti-GFAP antibody. Semi quantitative scoring in pericentral, periportal and perisinusoidal area of each case was done to assess immunoexpression of each marker. Results : Immunoexpression of GFAP showed significant association with α-SMA. GFAP expression was inversely correlated with progression of fibrosis. Conclusion : GFAP could represent a useful marker for early hepatic stellate cells activation. Follow up biopsies showing decline in GFAP levels may help identify the target group requiring aggressive therapy. PMID:25225520
Cheung, Victoria; Segal, Devorah; Gardner, Sharon L; Zagzag, David; Wisoff, Jeffrey H; Allen, Jeffrey C; Karajannis, Matthias A
2016-09-01
Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences.
Hernández, P; Dorado, G; Ramírez, M C; Laurie, D A; Snape, J W; Martín, A
2003-01-01
Hordeum chilense is a potential source of useful genes for wheat breeding. The use of this wild species to increase genetic variation in wheat will be greatly facilitated by marker-assisted introgression. In recent years, the search for the most suitable DNA marker system for tagging H. chilense genomic regions in a wheat background has lead to the development of RAPD and SCAR markers for this species. RAPDs represent an easy way of quickly generating suitable introgression markers, but their use is limited in heterogeneous wheat genetic backgrounds. SCARs are more specific assays, suitable for automatation or multiplexing. Direct sequencing of RAPD products is a cost-effective approach that reduces labour and costs for SCAR development. The use of SSR and STS primers originally developed for wheat and barley are additional sources of genetic markers. Practical applications of the different marker approaches for obtaining derived introgression products are described.
Elevated Endomyocardial Biopsy Macrophage-Related Markers in Intractable Myocardial Diseases.
Hayashi, Yuka; Hanawa, Haruo; Jiao, Shuang; Hasegawa, Go; Ohno, Yukako; Yoshida, Kaori; Suzuki, Tomoyasu; Kashimura, Takeshi; Obata, Hiroaki; Tanaka, Komei; Watanabe, Tohru; Minamino, Tohru
2015-12-01
Tissue macrophages can be activated by endogenous danger signals released from cells that are stressed or injured, leading to infiltration of inflammatory macrophages and neutrophils. We postulated that macrophage-related markers might be closely associated with the existence of endogenous danger signals, reflecting ongoing tissue injury in the absence of foreign substances. This study was designed to assess the ability of macrophage-related markers in endomyocardial biopsies to predict ongoing cardiac injury in non-inflammatory myocardial diseases. We examined levels of macrophage-related markers (CD68, CD163, CD45) in endomyocardial biopsies from patients (n = 86) with various myocardial diseases by quantitative reverse transcription-polymerase chain reaction (n = 78) and immunohistochemistry (n = 56). Thirty-three patients without inflammatory cardiac disease such as myocarditis and sarcoidosis were classified as "improved" or "non-improved" defined as a 10% increase in left ventricular ejection fraction by echocardiograph and a value greater than 30% at the time of follow-up. All macrophage-related (MacR) markers levels were not higher in non-improved dilated cardiomyopathy (DCM) patients than improved patients. However, patients with cardiac amyloidosis, cardiac Fabry disease, mitochondrial cardiomyopathy, and biventricular arrhythmogenic right ventricular cardiomyopathy (ARVC), which were categorized as "non-improvement diseases," had elevated macrophage-related markers compared to improved patients. Macrophage-related markers levels were increased in endomyocardial biopsy samples of patients with intractable myocardial diseases such as amyloidosis, mitochondrial disease, Fabry disease, and biventricular ARVC.
Petersen, Rikke A; Dalskov, Stine-Mathilde; Sørensen, Louise B; Hjorth, Mads F; Andersen, Rikke; Tetens, Inge; Krarup, Henrik; Ritz, Christian; Astrup, Arne; Michaelsen, Kim F; Mølgaard, Christian; Damsgaard, Camilla T
2015-11-28
Vitamin D status has been associated with cardiometabolic markers even in children, but the associations may be confounded by fat mass and physical activity behaviour. This study investigated associations between vitamin D status and cardiometabolic risk profile, as well as the impact of fat mass and physical activity in Danish 8-11-year-old children, using baseline data from 782 children participating in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. We assessed vitamin D status as serum 25-hydroxyvitamin D (25(OH)D) and measured blood pressure, fasting plasma glucose, homoeostasis model of assessment-insulin resistance, plasma lipids, inflammatory markers, anthropometry and fat mass by dual-energy X-ray absorptiometry, and physical activity by 7 d accelerometry during August-November. Mean serum 25(OH)D was 60·8 (sd 18·7) nmol/l. Each 10 mmol/l 25(OH)D increase was associated with lower diastolic blood pressure (-0·3 mmHg, 95 % CI -0·6, -0·0) (P=0·02), total cholesterol (-0·07 mmol/l, 95 % CI -0·10, -0·05), LDL-cholesterol (-0·05 mmol/l, 95 % CI -0·08, -0·03), TAG (-0·02 mmol/l, 95 % CI -0·03, -0·01) (P≤0·001 for all lipids) and lower metabolic syndrome (MetS) score (P=0·01). Adjustment for fat mass index did not change the associations, but the association with blood pressure became borderline significant after adjustment for physical activity (P=0·06). In conclusion, vitamin D status was negatively associated with blood pressure, plasma lipids and a MetS score in Danish school children with low prevalence of vitamin D deficiency, and apart from blood pressure the associations were independent of body fat and physical activity. The potential underlying cause-effect relationship and possible long-term implications should be investigated in randomised controlled trials.
2012-01-01
Background The deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging. Methods We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31). Results We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions. Conclusion Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging. PMID:22537877
The cellular immunity and oxidative stress markers in early pregnancy loss.
Daglar, Korkut; Biberoglu, Ebru; Kirbas, Ayse; Dirican, Aylin Onder; Genc, Metin; Avci, Aslihan; Biberoglu, Kutay
2016-01-01
We investigated whether changes in cellular immunity and oxidative stress in pregnancy have any association with spontaneous miscarriage. Circulating adenosine deaminase (ADA) activity as a marker of cellular immunity and malondialdehyde (MDA) and catalase (CAT), glutathione peroxidase (GPx) as markers of T lymphocyte activation and parameters of oxidative stress and antioxidant defense were compared between 40 women with early pregnancy loss and another 40 women with ungoing healthy pregnancy. Women with miscarriage had higher serum ADA and GPx levels when compared with women with normal pregnancy (p = 0.034 and p < 0.001, respectively). Although serum MDA level was slightly higher in women with miscarriage, the difference was not significant (p = 0.083). CAT levels were alike in both groups. We have demonstrated an increased cellular immunity and perhaps a compensated oxidative stress related to increased antioxidant activation in women with early spontaneous pregnancy loss.
Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Rodríguez, Sergio; Avanzas, Pablo; Juarez-Prera, Ruben A
2017-07-01
The aim of this study was to determine whether markers of inflammation and coagulation are associated with short-term particulate matter exposure and predict major adverse cardiovascular events at 360 d in patients with acute coronary syndrome (ACS). We included 307 consecutive patients, and assessed the average concentrations of data on atmospheric pollution in ambient air and meteorological variables from 1 d up to 7 d prior to admission. In patients with ACS, the markers of endothelial activation and coagulation, but not black carbon exposure, are associated with major adverse cardiovascular events at one-year follow-up.
Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity
Soloski, Mark J.; Crowder, Lauren A.; Lahey, Lauren J.; Wagner, Catriona A.
2014-01-01
Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. PMID:24740099
Seabra, André; Katzmarzyk, Peter; Carvalho, Maria José; Seabra, Ana; Coelho-E-Silva, Manuel; Abreu, Sandra; Vale, Susana; Póvoas, Susana; Nascimento, Henrique; Belo, Luís; Torres, Sandra; Oliveira, José; Mota, Jorge; Santos-Silva, Alice; Rêgo, Carla; Malina, Robert M
2016-10-01
Physical activity is important in obesity prevention, but the effectiveness of different physical activity modalities remains to be determined among children. The main purpose of this study was to compare the effects of a 6-month soccer programme and a traditional physical activity programme on changes in body composition, cardiometabolic risk factors, inflammatory and oxidative markers, cardiorespiratory fitness and perceived psychological status in obese boys. Eighty-eight boys (8-12 years; BMI > +2 standard deviations of WHO reference values) participated in one of three groups: soccer, traditional activity and control. Soccer and traditional activity programmes involved 3 sessions per week for 60-90 min at an average intensity of 70-80% of maximal heart rate. Control group participated in activities of normal daily living. All boys participated in school physical education, two sessions per week of 45-90-min. Measurements were taken at baseline and after 6 months, and included body size and composition, cardiometabolic risk factors, inflammatory and oxidative markers, cardiorespiratory fitness and perceived psychological status. Physical activity and dietary intake were assessed before and immediately following the intervention. The three groups had similar characteristics at baseline. After 6 months, both intervention groups had significantly lower relative fatness (% fat), waist circumference and total cholesterol, and higher cardiorespiratory fitness, self-esteem, perceived physical competence and attraction to physical activity compared with control group. In conclusion, physical activity interventions over 6 months positively influenced several indicators of health status among obese boys. The results also suggested that soccer has the potential as an effective tool for the prevention and reduction of childhood obesity and associated consequences.
Rocha, Adriana; Coelho, Eduardo B; Moussa, Soraia A P; Lanchote, Vera L
2008-09-01
This study compares midazolam with omeprazole as marker drugs for the evaluation of CYP3A activity in nine healthy self-reported white Brazilian volunteers. Omeprazole was also used to evaluate the CYP2C19 phenotype. The volunteers received p.o. 20 mg omeprazole, and blood samples were collected 3.5 h after drug administration. After a washout period of 10 days, the volunteers received p.o. 15 mg midazolam maleate, and serial blood samples were collected up to 6 h after administration of the drug. CYP2C19 was genotyped for the allelic variants CYP2C19*1, CYP2C19*2, CYP2C19*3, and CYP2C19*17. Analysis of omeprazole, hydroxyomeprazole, omeprazole sulfone, and midazolam in plasma was carried out by LC-MS/MS. The volunteers genotyped as CYP2C19*1*17, CYP2C19*17*17, CYP2C19*1*1 (n = 8), or CYP2C19*17*2 (n = 1) presented a median hydroxylation index (omeprazole/hydroxyomeprazole) of 1.35, indicating that all of them were extensive metabolizers of CYP2C19. The volunteers (n = 9) presented a 0.12 log of the omeprazole/sulfone ratio and a median oral clearance of midazolam of 17.89 ml min(-1) kg(-1), suggesting normal CYP3A activity. Orthogonal regression analysis between midazolam clearance and log of the plasma concentrations of the omeprazole/omeprazole sulfone ratio (R = -0.7544, P < 0.05) suggests that both midazolam and omeprazole can be used as markers of CYP3A activity in the population investigated.
Young, Leanne R; Yu, Weikei; Holloway, Michael; Rodgers, Barry N; Chapman, Sandra B; Krawczyk, Daniel C
2017-09-01
There has been great interest in characterizing the response of the amygdala to emotional faces, especially in the context of social cognition. Although amygdala activation is most often associated with fearful or angry stimuli, there is considerable evidence that the response of the amygdala to neutral faces is both robust and reliable. This characteristic of amygdala function is of particular interest in the context of assessing populations with executive function deficits, such as traumatic brain injuries, which can be evaluated using fMRI attention modulation tasks that evaluate prefrontal control over representations, notably faces. The current study tested the hypothesis that the amygdala may serve as a marker of selective attention to neutral faces. Using fMRI, we gathered data within a chronic traumatic brain injury population. Blood Oxygenation Level Dependent (BOLD) signal change within the left and right amygdalae and fusiform face areas was measured while participants viewed neutral faces and scenes, under conditions requiring participants to (1) categorize pictures of faces and scenes, (2) selectively attend to either faces or scenes, or (3) attend to both faces and scenes. Findings revealed that the amygdala is an effective marker for selective attention to neutral faces and, furthermore, it was more face-specific than the fusiform face area. Copyright © 2017 Elsevier Ltd. All rights reserved.
Serum Markers of Neurodegeneration in Maple Syrup Urine Disease.
Scaini, Giselli; Tonon, Tássia; de Souza, Carolina F Moura; Schuk, Patricia F; Ferreira, Gustavo C; Neto, Joao Seda; Amorin, Tatiana; Schwartz, Ida Vanessa D; Streck, Emilio L
2017-09-01
Maple syrup urine disease (MSUD) is an inherited disorder caused by deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their respective α-keto-acids. Patients affected by MSUD present severe neurological symptoms and brain abnormalities, whose pathophysiology is poorly known. However, preclinical studies have suggested alterations in markers involved with neurodegeneration. Because there are no studies in the literature that report the neurodegenerative markers in MSUD patients, the present study evaluated neurodegenerative markers (brain-derived neurotrophic factor (BDNF), cathepsin D, neural cell adhesion molecule (NCAM), plasminogen activator inhibitor-1 total (PAI-1 (total)), platelet-derived growth factor AA (PDGF-AA), PDGF-AB/BB) in plasma from 10 MSUD patients during dietary treatment. Our results showed a significant decrease in BDNF and PDGF-AA levels in MSUD patients. On the other hand, NCAM and cathepsin D levels were significantly greater in MSUD patients compared to the control group, while no significant changes were observed in the levels of PAI-1 (total) and PDGF-AB/BB between the control and MSUD groups. Our data show that MSUD patients present alterations in proteins involved in the neurodegenerative process. Thus, the present findings corroborate previous studies that demonstrated that neurotrophic factors and lysosomal proteases may contribute, along with other mechanisms, to the intellectual deficit and neurodegeneration observed in MSUD.
Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men.
Williams, Lana J; Berk, Michael; Hodge, Jason M; Kotowicz, Mark A; Stuart, Amanda L; Chandrasekaran, Vinoomika; Cleminson, Jasmine; Pasco, Julie A
2018-02-13
Selective serotonin reuptake inhibitors (SSRIs) have been shown to have a clinically significant impact on bone metabolism. To explore this further, we aimed to determine whether these agents are associated with serum markers of bone turnover utilising a population-based sample of men (n = 1138; 20-96 year) participating in the Geelong Osteoporosis Study. Blood samples were obtained and the bone resorption marker, C-telopeptide (CTx) and formation marker, type 1 procollagen amino-terminal-propeptide (PINP) were measured. Anthropometry and socio-economic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Lifetime mood disorders were assessed using semi-structured clinical interviews. Thirty-seven (3.3%) men reported using SSRIs. Age was an effect modifier in the association between SSRIs and markers of bone turnover. Among younger men (20-60 year; n = 557), adjusted mean CTx and PINP values were 12.4% [16.7 (95% CI 14.6-18.8) vs 19.1 (95% CI 18.7-19.4) pg/ml, p = 0.03] and 13.6% [5.6 (95% CI 4.9-6.3) vs 6.4 (95% CI 6.3-6.6) pg/ml, p = 0.02] lower among SSRI users compared to non-users, respectively. No differences in SSRI use and markers of bone turnover were detected among older men (61-94 year; all p > 0.05). These patterns persisted after further adjustment for activity, alcohol, smoking, SES, depression, bone active medications and other antidepressants. Our data suggest that SSRI use is associated with alterations in bone turnover markers among younger men. The observed decreases in both CTx and PINP are likely to contribute to a low bone turnover state and increased skeletal fragility with this potential imbalance between formation and resorption resulting in subsequent bone loss.
Liao, Maoliang; Shang, Haihua; Li, Yazhuo; Li, Tian; Wang, Miao; Zheng, Yanan; Hou, Wenbin; Liu, Changxiao
2018-06-01
Quality control of traditional Chinese medicines is currently a great concern, due to the correlation between the quality control indicators and clinic effect is often questionable. According to the "multi-components and multi-targets" property of TCMs, a new special quality and bioactivity evaluation system is urgently needed. Present study adopted an integrated approach to provide new insights relating to uncover quality marker underlying the effects of Alisma orientale (AO) on lipid metabolism. In this paper, guided by the concept of the quality marker (Q-marker), an integrated strategies "effect-compound-target-fingerprint" was established to discovery and screen the potential quality marker of AO based on network pharmacology and chemical analysis. Firstly, a bioactivity evaluation was performed to screen the main active fractions. Then the chemical compositions were rapidly identified by chemical analysis. Next, networks were constructed to illuminate the interactions between these component and their targets for lipid metabolism, and the potential Q-marker of AO was initially screened. Finally, the activity of the Q-markers was validated in vitro. 50% ethanol extract fraction was found to have the strongest lipid-lowering activity. Then, the network pharmacology was used to clarify the unique relationship between the Q-markers and their integral pharmacological action. Combined with the results obtained, five active ingredients in the 50% ethanol extract fraction were given special considerations to be representative Q-markers: Alisol A, Alisol B, Alisol A 23-acetate, Alisol B 23-acetate and Alisol A 24-acetate, respectively. The chromatographic fingerprints based Q-marker was establishment. The integrated Q-marker screen may offer an alternative quality assessment of herbal medicines. Copyright © 2018. Published by Elsevier GmbH.
Pawlak, Krystyna; Mysliwiec, Michal; Pawlak, Dariusz
2015-04-01
Endocan is a new marker of endothelial cell activation that mediates adhesion of leukocytes into endothelium. Soluble intercellular (sICAM-1) and vascular cellular (sVCAM-1) adhesion molecules play an important role in the prevalence of cardiovascular disease (CVD) in chronic kidney disease (CKD) patients. The aim of this study is to investigate whether endocan could affect the concentrations of sICAM-1 and sVCAM-1 in CKD patients, particularly in those with CVD. We evaluated plasma endocan, sICAM-1, sVCAM-1 and the markers of inflammation: high sensitivity C-reactive protein (hs CRP), interleukin-6, tumor necrosis factor-α (TNF-α) and their interrelationships in 53 CKD patients (both with and without CVD) and 29 healthy controls. Endocan, sICAM-1, sVCAM-1 and inflammatory markers were significantly higher in CKD patients than in controls, and patients with CVD had levels significantly higher (except interleukin-6 and TNF-α) than those without CVD. The presence of CVD, ferritin, TNF-α and SBP were the independent predictors of endocan levels in the whole CKD group. In this group, the weak relationship was between endocan and sICAM-1 and sVCAM-1, but age was the only independent predictor of these adhesion molecules. The strong association between endocan and sICAM-1 and sVCAM-1 was exclusively observed in subgroup with CVD, and the low % of lymphocytes followed by increased endocan was identified as the independent variables significantly associated with these soluble molecule levels. This study shows that plasma endocan is significantly increased and independently associated with sICAM-1 and sVCAM-1 levels in CKD patients with cardiovascular complications. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Li, Chenhong; Riethoven, Jean-Jack M; Naylor, Gavin J P
2012-09-01
Recent innovations in next-generation sequencing have lowered the cost of genome projects. Nevertheless, sequencing entire genomes for all representatives in a study remains expensive and unnecessary for most studies in ecology, evolution and conservation. It is still more cost-effective and efficient to target and sequence single-copy nuclear gene markers for such studies. Many tools have been developed for identifying nuclear markers, but most of these have focused on particular taxonomic groups. We have built a searchable database, EvolMarkers, for developing single-copy coding sequence (CDS) and exon-primed-intron-crossing (EPIC) markers that is designed to work across a broad range of phylogenetic divergences. The database is made up of single-copy CDS derived from BLAST searches of a variety of metazoan genomes. Users can search the database for different types of markers (CDS or EPIC) that are common to different sets of input species with different divergence characteristics. EvolMarkers can be applied to any taxonomic group for which genome data are available for two or more species. We included 82 genomes in the first version of EvolMarkers and have found the methods to be effective across Placozoa, Cnidaria, Arthropod, Nematoda, Annelida, Mollusca, Echinodermata, Hemichordata, Chordata and plants. We demonstrate the effectiveness of searching for CDS markers within annelids and show how to find potentially useful intronic markers within the lizard Anolis. © 2012 Blackwell Publishing Ltd.
Javed, Mehjbeen; Ahmad, Irshad; Ahmad, Ajaz; Usmani, Nazura; Ahmad, Masood
2016-01-01
The present study was conducted to assess the toxicity of thermal power plant effluent containing heavy metals (Fe > Cu > Zn > Mn > Ni > Co > Cr) on haematological indices, micronuclei, lobed nuclei and activity of pathological marker enzymes [alkaline phosphatase (ALP), aspartate transferase (AST), alanine transferase (ALT) and creatine kinase (CK)] in Channa punctatus. Total erythrocyte count (-54.52 %), hemoglobin (-36.98 %), packed cell volume (-36.25 %), mean corpuscular hemoglobin concentration (-1.41 %) and oxygen (O2) carrying capacity (-37.04 %) declined significantly over reference fish, however total leukocyte count (+25.43 %), mean corpuscular hemoglobin (+33.52 %) and mean corpuscular volume (+35.49 %) showed elevation. High frequency of micronuclei (1133.3 %) and lobed nuclei (150 %) were observed in exposed fish which may indicate mutagenesis. Activities of pathological marker enzymes ALP, AST, ALT and CK increased significantly in serum of exposed fish. The ratio of ALT: AST in exposed fish was beyond 1 which indicates manifestation of pathological processes. These biomarkers show that fish have macrocytic hypochromic anemia. Leukocytosis showed general defence response against heavy metal toxicity and marker enzymes showed tissue degeneration. In conclusion, thermal power plant effluent has strong potential to induce micronuclei, tissue pathology, making the fish anemic, weak, stressed and vulnerable to diseases.
Chhor, Vibol; Le Charpentier, Tifenn; Lebon, Sophie; Oré, Marie-Virgine; Celador, Idoia Lara; Josserand, Julien; Degos, Vincent; Jacotot, Etienne; Hagberg, Henrik; Sävman, Karin; Mallard, Carina; Gressens, Pierre; Fleiss, Bobbi
2013-01-01
Microglia mediate multiple facets of neuroinflammation, including cytotoxicity, repair, regeneration, and immunosuppression due to their ability to acquire diverse activation states, or phenotypes. Modulation of microglial phenotype is an appealing neurotherapeutic strategy but a comprehensive study of classical and more novel microglial phenotypic markers in vitro is lacking. The aim of this study was to outline the temporal expression of a battery of phenotype markers from polarised microglia to generate an in vitro tool for screening the immunomodulatory potential of novel compounds. We characterised expression of thirty-one macrophage/microglial phenotype markers in primary microglia over time (4, 12, 36, and 72 h), using RT-qPCR or multiplex protein assay. Firstly, we selected Interleukin-4 (IL-4) and lipopolysaccharide (LPS) as the strongest M1–M2 polarising stimuli, from six stimuli tested. At each time point, markers useful to identify that microglia were M1 included iNOS, Cox-2 and IL-6 and a loss of M2a markers. Markers useful for quantifying M2b-immunomodulatory microglia included, increased IL-1RA and SOCS3 and for M2a-repair and regeneration, included increased arginase-1, and a loss of the M1 and M2b markers were discriminatory. Additional markers were regulated at fewer time points, but are still likely important to monitor when assessing the immunomodulatory potential of novel therapies. Further, to facilitate identification of how novel immunomodulatory treatments alter the functional affects of microglia, we characterised how the soluble products from polarised microglia affected the type and rate of neuronal death; M1/2b induced increasing and M2a-induced decreasing neuronal loss. We also assessed any effects of prior activation state, to provide a way to identify how a novel compound may alter phenotype depending on the stage of injury/insult progression. We identified generally that a prior M1/2b reduced the ability of microglia to switch to
Immune modulation following immunization with polyvalent vaccines in dogs.
Strasser, Alois; May, Bettina; Teltscher, Andrea; Wistrela, Eva; Niedermüller, Hans
2003-08-15
A decline in T-cell-mediated immunity and transient state of immunosuppression after immunization has been reported in dogs. Nevertheless, dogs are still routinely vaccinated with polyvalent live vaccines and severe disease does not generally occur. In order to investigate these effects on the canine immune system and to elucidate possible mechanisms we determined the following immune parameters in the blood of 33 clinically sound German shepherd dogs before and after standard vaccination with a polyvalent vaccine against distemper, parvovirus, viral hepatitis, leptospirosis, kennel cough and rabies: white and differential blood cell count, the serum concentrations and/or activities of IL-1, IL-2, IFN-gamma, TNF-alpha, neopterin and IgG, natural killer (NK) cell activity, bactericidal activity and complement hemolytic activity, lymphocyte proliferation test (LPT) and nitroblue tetrazolium test (NBT). Our major findings were that significant postvaccinal decreases in T-cell mitogenic response to PHA and in neutrophil function and neopterin serum concentration were accompanied by simultaneous increase in plasma IgG and hemolytic complement activity. This suggests a transient shift in the balance between cell-mediated and humoral (T(H)1/T(H)2) immunity rather than immunosuppression. These results do not imply that dogs should not receive live vaccines, as the response to vaccines just seems to create a state of altered homeostasis when immunization elicits protection by humoral and cell-mediated immunity. However, these recognized compromises of immune function should be considered and vaccines still be applied only in healthy animals and strictly according to the rules and regulations given by the manufacturer.
Choi, Ivy Y; Karpus, Olga N; Turner, Jason D; Hardie, Debbie; Marshall, Jennifer L; de Hair, Maria J H; Maijer, Karen I; Tak, Paul P; Raza, Karim; Hamann, Jörg; Buckley, Christopher D; Gerlag, Danielle M; Filer, Andrew
2017-01-01
Previous studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied. ST from 56 patients included in two different early arthritis cohorts and 7 non-inflammatory controls was analysed using immunofluorescence to detect stromal markers CD55, CD248, fibroblast activation protein (FAP) and podoplanin. Diagnostic classification (gout, psoriatic arthritis, unclassified arthritis (UA), parvovirus associated arthritis, reactive arthritis and RA), disease outcome (resolving vs persistent) and clinical variables were determined at baseline and after follow-up, and related to the expression of stromal markers. We observed expression of all stromal markers in ST of early arthritis patients, independent of diagnosis or prognostic outcome. Synovial expression of FAP was significantly higher in patients developing early RA compared to other diagnostic groups and non-inflammatory controls. In RA FAP protein was expressed in both lining and sublining layers. Podoplanin expression was higher in all early inflammatory arthritis patients than controls, but did not differentiate diagnostic outcomes. Stromal marker expression was not associated with prognostic outcomes of disease persistence or resolution. There was no association with clinical or sonographic variables. Stromal cell markers CD55, CD248, FAP and podoplanin are expressed in ST in the earliest stage of arthritis. Baseline expression of FAP is higher in early synovitis patients who fulfil classification criteria for RA over time. These results suggest that significant fibroblast activation occurs in RA in the early window of disease.
Molecular cloning and characterization of markers and cytokines for equid myeloid cells.
Steinbach, Falko; Stark, Robert; Ibrahim, Sherif; Gawad, Eman Abd-El; Ludwig, Hanns; Walter, Jakob; Commandeur, Ulrich; Mauel, Susanne
2005-10-18
The myeloid cell system comprises of monocytes, macrophages (MPhi), dendritic cells (DC), Kupffer cells, osteoclasts or microglia and is also known as the mononuclear phagocytic system (MPS). Essential cytokines to differentiate or activate these cells include GM-CSF or IL-4. Important markers for characterization include CD1, CD14, CD68, CD163 and CD206. All these markers, however, were not cloned or further characterized in equids by use of monoclonal antibodies earlier. To overcome this problem with the present study, two approaches were used. First, we cloned equine cytokines and markers, and second we analyzed cross-reactivity of human homologues or anti-human monoclonal antibodies. For cloning of equine cytokines and markers, we used degenerate primers delineated from other species, or equine-specific primers based on previous information in Genbank. Flow cytometry was used to determine the expression of markers on myeloid cells. Cross-reactivity could be shown for anti-human CD14, CD163 and mannose receptor (CD206) mAbs. Surface markers such as CD1 and CD68 that distinguish MPhi and DC were cloned and sequenced. According to blast homology, equine CD1a and CD1b could be identified and distinguished. With the resulting information, dendritic cells and macrophages of horses may be characterized.
Christensen, Jon; Bentz, Susanne; Sengstag, Thierry; Shastri, V. Prasad; Anderle, Pascale
2013-01-01
Background The forkhead box transcription factor FOXQ1 has been shown to be upregulated in colorectal cancer (CRC) and metastatic breast cancer and involved in tumor development, epithelial-mesenchymal transition and chemoresistance. Yet, its transcriptional regulation is still unknown. Methods FOXQ1 mRNA and protein expression were analysed in a panel of CRC cell lines, and laser micro-dissected human biopsy samples by qRT-PCR, microarray GeneChip® U133 Plus 2.0 and western blots. FOXQ1 regulation was assayed by chromatin immunoprecipitation and luciferase reporter assays. Results FOXQ1 was robustly induced in CRC compared to other tumors, but had no predictive value with regards to grade, metastasis and survival in CRC. Prototype-based gene coexpression and gene set enrichment analysis showed a significant association between FOXQ1 and the Wnt pathway in tumors and cancer cell lines from different tissues. In vitro experiments confirmed, on a molecular level, FOXQ1 as a direct Wnt target. Analysis of known Wnt targets identified FOXQ1 as the most suitable marker for canonical Wnt activation across a wide panel of cell lines derived from different tissues. Conclusions Our data show that FOXQ1 is one of the most over-expressed genes in CRC and a direct target of the canonical Wnt pathway. It is a potential new marker for detection of early CRC and Wnt activation in tumors of different origins. PMID:23555880
Friedenreich, Christine M; Pialoux, Vincent; Wang, Qinggang; Shaw, Eileen; Brenner, Darren R; Waltz, Xavier; Conroy, Shannon M; Johnson, Rhys; Woolcott, Christy G; Poulin, Marc J; Courneya, Kerry S
2016-01-01
Background Oxidative stress may contribute to cancer aetiology through several mechanisms involving damage to DNA, proteins and lipids leading to genetic mutations and genomic instability. The objective of this study was to determine the effects of aerobic exercise on markers of oxidative damage and antioxidant enzymes in postmenopausal women. Methods The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA) was a two-centre, two-armed randomised trial of 320 inactive, healthy, postmenopausal women aged 50–74 years. Participants were randomly assigned to a year-long exercise intervention (225 min/week) or a control group while being asked to maintain a normal diet. Fasting blood samples were obtained and plasma concentrations of two oxidative damage markers (8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-Iso-PGF2α)) and two antioxidant enzymes (superoxide dismutase and catalase) were measured at baseline, 6 months and 12 months. Intention-to-treat (ITT) and per-protocol analyses were performed using linear mixed models adjusted for baseline biomarker concentrations. A further exercise adherence analysis, based on mean minutes of exercise per week, was also performed. Results In the ITT and per-protocol analyses, the exercise intervention did not have any statistically significant effect on either oxidative damage biomarkers or antioxidant enzyme activity. Conclusions A year-long aerobic exercise intervention did not have a significant impact on oxidative stress in healthy, postmenopausal women. Trial registration number NCT00522262. PMID:27900199
Palma, Marzia; Gentilcore, Giusy; Heimersson, Kia; Mozaffari, Fariba; Näsman-Glaser, Barbro; Young, Emma; Rosenquist, Richard; Hansson, Lotta; Österborg, Anders; Mellstedt, Håkan
2017-03-01
Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3 + cells and the CD8 + subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4 + and CD8 + cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients ( P =0.0003 and P =0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4 + and CD8 + subsets, with a significantly higher PD-1 expression. Higher numbers of CD4 + and CD8 + cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67 + ) and activated (CD69 + ) CD4 + and CD8 + cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls ( P <0.05), albeit decreasing to low levels in pre-treated patients. In conclusion, chronic lymphocytic leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways. Copyright© Ferrata Storti Foundation.
Sex-based differences in plasma chemistry and cardiac marker test results in Siamese fighting fowl.
Sribhen, Choosri; Choothesa, Apassara; Songserm, Thaveesak; Issariyodom, Supaporn; Sribhen, Kosit
2006-09-01
Variations in the results of plasma chemistry analysis as a function of sex have rarely been demonstrated in avian species. The aim of the present study was to investigate sex-related differences in values for routine biochemical variables, including conventional muscle enzymes, and novel cardiac markers in female and male Siamese fighting fowl. Plasma chemistry analytes and cardiac marker proteins (creatine kinase-MB and cardiac troponin T) were measured in 70 Siamese fighting fowl using automated chemistry and immunoassay analyzers. Data were compared by 2-tailed t tests between sexes, and Spearman rank correlation between conventional and novel cardiac markers. Male fowl had significantly higher uric acid concentration and gamma-glutamyltransferase activity; whereas, female fowl had significantly higher total cholesterol, triglycerides, and calcium concentrations, and alkaline phosphatase activity. As compared with female fowl, the fighting cocks also had significantly higher plasma concentrations of creatine kinase-MB and cardiac troponin T. Significant correlations between cardiac troponin T, but not creatine kinase-MB, and the activities of conventional muscle enzymes (creatine kinase, aspartate aminotransferase and lactate dehydrogenase) were observed in male but not in female fowl. These results indicate that sex-specific differences exist for several biochemical parameters and cardiac marker proteins in fighting fowl, and that such differences should be considered in interpreting laboratory test results.
Aged keratinocyte phenotyping: morphology, biochemical markers and effects of Dead Sea minerals.
Soroka, Yoram; Ma'or, Zeev; Leshem, Yael; Verochovsky, Lilian; Neuman, Rami; Brégégère, François Menahem; Milner, Yoram
2008-10-01
The aging process and its characterization in keratinocytes have not been studied in depth until now. We have assessed the cellular and molecular characteristics of aged epidermal keratinocytes in monolayer cultures and in skin by measuring their morphological, fluorometric and biochemical properties. Light and electron microscopy, as well as flow cytometry, revealed increase in cell size, changes in cell shape, alterations in mitochondrial structure and cytoplasmic content with aging. We showed that the expression of 16 biochemical markers was altered in aged cultured cells and in tissues, including caspases 1 and 3 and beta-galactosidase activities, immunoreactivities of p16, Ki67, 20S proteasome and effectors of the Fas-dependent apoptotic pathway. Aged cells diversity, and individual variability of aging markers, call for a multifunctional assessment of the aging phenomenon, and of its modulation by drugs. As a test case, we have measured the effects of Dead Sea minerals on keratinocyte cultures and human skin, and found that they stimulate proliferation and mitochondrial activity, decrease the expression of some aging markers, and limit apoptotic damage after UVB irradiation.
Biological markers of melancholia and reclassification of depressive disorders.
Greden, J F
1982-01-01
Pathophysiological markers of melancholia are being developed in four major areas: 1) neuroendocrine; 2) sleep; 3) psychomotor and 4) biochemical. Neuroendocrine markers include a failure of suppress plasma cortisol secretion in the dexamethasone suppression test (DST), diminished thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH stimulation test), and blunted growth hormone response to a variety of stimulating agents such as d-amphetamine, methylamphetamine, clonidine, L-dopa and insulin (growth hormone test). Of these, the DST is the best standardized. It is a highly specific laboratory marker with documented value in diagnosis, assessing prognosis and monitoring treatment progress. Sleep EEG abnormalities include reduced REM latency, increased REM density, reduction in delta sleep and impaired sleep efficiency. Sleep EEGs are pragmatically difficult, but results are quite specific. Elongated speech pause time (SPT) during "automatic speech" is a promising marker of psychomotor regulation. This simple, non-invasive measure may have special value in reducing clinical subjectivity and in monitoring treatment progress. Biochemical markers include: 1) platelet monoamine oxidase (MAO) activity; 2) in vitro lithium RBC transport and 3) urinary MHPG levels. Standardizations of biochemical tests are still lacking. Most biological tests for melancholia operate by indirectly "marking" CNS limbic system dysfunction. For wide acceptance, a test must be safe, moderately sensitive, highly specific, practical, relatively inexpensive and not significantly altered by common anti-depressant treatments. The DST best meets these criteria at this time. Proper utilization of test results requires knowledge of baseline prevalence rates and of the concepts of sensitivity (true-positive rate), specificity (true negative rate) and positive and negative predictive values (diagnostic confidence). No single marker will meet all clinical needs. Combinations or serial use of
Cichocka-Jarosz, Ewa; Dorynska, Agnieszka; Pietrzyk, Jacek J; Spiewak, Radoslaw
2011-08-01
To evaluate markers of mast cell and basophil activation in children undergoing the initial phase of honeybee venom immunotherapy (VIT). Five children (four boys and one girl) aged 9.5-18 years with severe systemic bee sting reactions and confirmed IgE-mediated allergy were enrolled. Plasma and urine concentrations of 9α,11β-PGF2 and serum tryptase levels were measured at four time points and peripheral blood basophil count and CD63 expression were measured at three time points in the course of VIT, including 5-day rush initial immunotherapy (cumulative dose of 223 µg of bee venom allergen) and two subsequent maintenance doses of 100 µg. In the first 40 days of VIT, there was a decrease in mean plasma levels of 9α,11β-PGF2 (from 41.5 to 27.9 pg/ml; p < 0.05), accompanied by an increase in baseline basophil activation (from 2 to 15%; p < 0.05). The median serum tryptase levels increased from 3.45 to 4.40 ng/ml during rush phase and subsequently returned to initial values (statistically not significant). In four patients, the basophil activation test in response to bee venom allergens remained positive throughout the study. The fifth patient was basophil activation test-negative at all three measurements, and a post hoc analysis revealed clinical peculiarities that are discussed in the paper. Our preliminary results indicate that plasma levels of 9α,11β-PGF2 decrease while numbers of activated basophils increase during the initial phase of bee venom rush immunotherapy in children.
Vondrichova, Tereza; de Capretz, Annika; Parikh, Hemang; Frenander, Christofer; Asman, Peter; Aberg, Magnus; Groop, Leif; Hallengren, Bengt; Lantz, Mikael
2007-06-01
Inflammation and adipogenesis are two parallel processes with increased activity in severe Graves' ophthalmopathy. The aim of this work was to define target genes for therapeutic intervention in adipogenesis and inflammation in Graves' ophthalmopathy. Orbital tissue was obtained from patients with ophthalmopathy in acute or chronic phase undergoing orbital surgery to study gene expression followed by the study of potential intervention mechanisms in preadipocytes. Clinic of Endocrinology, University Hospital, Malmö, Sweden. Patients in acute severe or in chronic phase of ophthalmopathy. Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In vitro treatment of preadipocytes with rosiglitazone and diclofenac. Gene expression in intraorbital tissue or preadipocytes and differentiation of preadipocytes. A marker of adipose tissue, stearoyl-coenzyme A desaturase (SCD), and the proinflammatory gene, cyclooxygenase-2 (COX-2), were overexpressed in patients in active phase compared to the chronic phase of ophthalmopathy. In growth-arrested preadipocytes stimulated with rosiglitazone, COX-2 expression increased temporarily within 1 hour and decreased to undetectable levels after 48 hours. In contrast, SCD and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression increased continuously from day 2 to day 7 during adipogenesis. Diclofenac, an inhibitor of cyclooxygenases with antagonistic effects on PPAR-gamma, reduced the number of mature adipocytes by approximately 50%. We conclude that inflammation and adipogenesis decrease with a decrease in activity of ophthalmopathy and that the nonsteroidal antiinflammatory drug diclofenac inhibits adipogenesis. This may represent a putative future treatment of endocrine ophthalmopathy.
DNA markers in molecular diagnostics for hepatocellular carcinoma
Su, Ying-Hsiu; Lin, Selena Y; Song, Wei; Jain, Surbhi
2015-01-01
Hepatocellular carcinoma (HCC) is the one of the leading causes of cancer mortality in the world, mainly due to the difficulty of early detection and limited therapeutic options. The implementation of HCC surveillance programs in well-defined, high-risk populations were only able to detect about 40–50% of HCC at curative stages (Barcelona Clinic Liver Cancer stages 0 & 1) due to the low sensitivities of the current screening methods. The advance of sequencing technologies has identified numerous modifications as potential candidate DNA markers for diagnosis/surveillance. Here we aim to provide an overview of the DNA alterations that result in activation of cancer pathways known to potentially drive HCC carcinogenesis and to summarize performance characteristics of each DNA marker in the periphery (blood or urine) for HCC screening. PMID:25098554
Gama, Túlio Gustavo Veiga; Pires, Fabio Ramoa; Armada, Luciana; Gonçalves, Lucio Souza
2016-06-01
This study tested the hypothesis that the inflammatory cell profile (CD3-, CD4-, CD8-, CD20-, and CD68-positive cells) and the expression of immunologic markers (tumor necrosis factor α, interferon-γ, interleukin-6, and interleukin-18) in chronic apical periodontitis are the same between non-HIV-infected patients and HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Thirty-four surgically excised chronic apical periodontitis lesions were sampled from 34 patients (17 HIV-infected and 17 non-HIV-infected). The lesions were extracted from teeth with no previous endodontic treatment. All HIV-infected patients were undergoing HAART. The specimens were submitted to histopathologic and immunohistochemical analyses by using an optical microscope. Immunoexpression was graded into 2 levels, focal to weak and moderate to strong. The χ(2), Fisher exact, and Mann-Whitney tests were used to analyze all significant differences between groups. Periapical cysts represented 70.6% and 52.9% of the lesions in the HIV-infected and non-HIV-infected groups, respectively; however, no statistically significant difference was observed (P = .481). There were no statistically significant differences between groups for the inflammatory cell profile and for any of the immunologic markers (P > .05). There are no statistically significant differences of the cellular profile and expression of immunologic markers in chronic apical periodontitis between non-HIV-infected patients and HIV-infected patients undergoing HAART. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-28
...-AA00 Natchez Fireworks Safety Zone; Lower Mississippi River, Mile Marker 365.5 to Mile Marker 363... establishing a temporary safety zone for all waters of the Lower Mississippi River from mile marker 365.5 to... from mile marker 365.5 to 363 extending the entire width [[Page 59621
Canonical Wnt Signaling as a Specific Marker for Normal and Tumorigenic Mammary Stem Cells
2012-02-01
These cells were identified by flow cytometry to detect cells that were positive for CD24 and CD49f. 2. We have established that activation of Wnt...09-1-0072 TITLE: Canonical Wnt Signaling as a Specific marker for Normal and Tumorigenic Mammary Stem Cells PRINCIPAL...activation of canonical Wnt signaling may be a very specific marker for mammary stem cells and be a target for transformation that results in the
Mueller, Henrik; Faé, Kellen C.; Magdorf, Klaus; Ganoza, Christian A.; Wahn, Ulrich; Guhlich, Ute; Feiterna-Sperling, Cornelia; Kaufmann, Stefan H. E.
2011-01-01
Background Granulysin produced by cytolytic T cells directly contributes to immune defense against tuberculosis (TB). We investigated granulysin as a candidate immune marker for childhood and adolescent TB. Methods Peripheral blood mononuclear cells (PBMC) from children and adolescents (1–17 years) with active TB, latent TB infection (LTBI), nontuberculous mycobacteria (NTM) infection and from uninfected controls were isolated and restimulated in a 7-day restimulation assay. Intracellular staining was then performed to analyze antigen-specific induction of activation markers and cytotoxic proteins, notably, granulysin in CD4+ CD45RO+ memory T cells. Results CD4+ CD45RO+ T cells co-expressing granulysin with specificity for Mycobacterium tuberculosis (Mtb) were present in high frequency in TB-experienced children and adolescents. Proliferating memory T cells (CFSElowCD4+CD45RO+) were identified as main source of granulysin and these cells expressed both central and effector memory phenotype. PBMC from study participants after TB drug therapy revealed that granulysin-expressing CD4+ T cells are long-lived, and express several activation and cytotoxicity markers with a proportion of cells being interferon-gamma-positive. In addition, granulysin-expressing T cell lines showed cytolytic activity against Mtb-infected target cells. Conclusions Our data suggest granulysin expression by CD4+ memory T cells as candidate immune marker for TB infection, notably, in childhood and adolescence. PMID:22216262
Dendritic cell co-stimulatory and co-inhibitory markers in chronic HCV: An Egyptian study
Fouad, Hanan; Raziky, Maissa Saeed El; Aziz, Rasha Ahmed Abdel; Sabry, Dina; Aziz, Ghada Mahmoud Abdel; Ewais, Manal; Sayed, Ahmed Reda
2013-01-01
AIM: To assess co-stimulatory and co-inhibitory markers of dendritic cells (DCs) in hepatitis C virus (HCV) infected subjects with and without uremia. METHODS: Three subject groups were included in the study: group 1 involved 50 control subjects, group 2 involved 50 patients with chronic HCV infection and group 3 involved 50 HCV uremic subjects undergoing hemodialysis. CD83, CD86 and CD40 as co-stimulatory markers and PD-L1 as a co-inhibitory marker were assessed in peripheral blood mononuclear cells by real-time polymerase chain reaction. Interleukin-10 (IL-10) and hyaluronic acid (HA) levels were also assessed. All findings were correlated with disease activity, viral load and fibrogenesis. RESULTS: There was a significant decrease in co-stimulatory markers; CD83, CD86 and CD40 in groups 2 and 3 vs the control group. Co-stimulatory markers were significantly higher in group 3 vs group 2. There was a significant elevation in PD-L1 in both HCV groups vs the control group. PD-L1 was significantly lower in group 3 vs group 2. There was a significant elevation in IL-10 and HA levels in groups 2 and 3, where IL-10 was higher in group 3 and HA was lower in group 3 vs group 2. HA level was significantly correlated with disease activity and fibrosis grade in group 2. IL-10 was significantly correlated with fibrosis grade in group 2. There were significant negative correlations between co-stimulatory markers and viral load in groups 2 and 3, except CD83 in dialysis patients. There was a significant positive correlation between PD-L1 and viral load in both HCV groups. CONCLUSION: A significant decrease in DC co-stimulatory markers and a significant increase in a DC co-inhibitory marker were observed in HCV subjects and to a lesser extent in dialysis patients. PMID:24282359
Jones, Simon P.; Franco, Nunzio F.; Varney, Bianca; Sundaram, Gayathri; Brown, David A.; de Bie, Josien; Lim, Chai K.; Guillemin, Gilles J.; Brew, Bruce J.
2015-01-01
The kynurenine pathway is a fundamental mechanism of immunosuppression and peripheral tolerance. It is increasingly recognized as playing a major role in the pathogenesis of a wide variety of inflammatory, neurodegenerative and malignant disorders. However, the temporal dynamics of kynurenine pathway activation and metabolite production in human immune cells is currently unknown. Here we report the novel use of flow cytometry, combined with ultra high-performance liquid chromatography and gas chromatography-mass spectrometry, to sensitively quantify the intracellular expression of three key kynurenine pathway enzymes and the main kynurenine pathway metabolites in a time-course study. This is the first study to show that up-regulation of indoleamine 2,3-dioxygenase (IDO-1), kynurenine 3-monoxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) is lacking in lymphocytes treated with interferon gamma. In contrast, peripheral monocytes showed a significant elevation of kynurenine pathway enzymes and metabolites when treated with interferon gamma. Expression of IDO-1, KMO and QPRT correlated significantly with activation of the kynurenine pathway (kynurenine:tryptophan ratio), quinolinic acid concentration and production of the monocyte derived, pro-inflammatory immune response marker: neopterin. Our results also describe an original and sensitive methodological approach to quantify kynurenine pathway enzyme expression in cells. This has revealed further insights into the potential role of these enzymes in disease processes. PMID:26114426
Li, Li; Tacke, Eckhard; Hofferbert, Hans-Reinhardt; Lübeck, Jens; Strahwald, Josef; Draffehn, Astrid M; Walkemeier, Birgit; Gebhardt, Christiane
2013-04-01
Tuber yield, starch content, starch yield and chip color are complex traits that are important for industrial uses and food processing of potato. Chip color depends on the quantity of reducing sugars glucose and fructose in the tubers, which are generated by starch degradation. Reducing sugars accumulate when tubers are stored at low temperatures. Early and efficient selection of cultivars with superior yield, starch yield and chip color is hampered by the fact that reliable phenotypic selection requires multiple year and location trials. Application of DNA-based markers early in the breeding cycle, which are diagnostic for superior alleles of genes that control natural variation of tuber quality, will reduce the number of clones to be evaluated in field trials. Association mapping using genes functional in carbohydrate metabolism as markers has discovered alleles of invertases and starch phosphorylases that are associated with tuber quality traits. Here, we report on new DNA variants at loci encoding ADP-glucose pyrophosphorylase and the invertase Pain-1, which are associated with positive or negative effect with chip color, tuber starch content and starch yield. Marker-assisted selection (MAS) and marker validation were performed in tetraploid breeding populations, using various combinations of 11 allele-specific markers associated with tuber quality traits. To facilitate MAS, user-friendly PCR assays were developed for specific candidate gene alleles. In a multi-parental population of advanced breeding clones, genotypes were selected for having different combinations of five positive and the corresponding negative marker alleles. Genotypes combining five positive marker alleles performed on average better than genotypes with four negative alleles and one positive allele. When tested individually, seven of eight markers showed an effect on at least one quality trait. The direction of effect was as expected. Combinations of two to three marker alleles were
Liu, Wen; Moulay, Mohammed; Willenbrock, Saskia; Roolf, Catrin; Junghanss, Christian; Ngenazahayo, Anaclet; Nolte, Ingo; Murua Escobar, Hugo
2015-04-01
Canine prostate cancer represents a spontaneous animal model for the human counterpart. Cells with stem cell-like character are considered to play a major role in therapeutic resistance and tumor relapse. Thus, the identification of markers allowing for recognition and characterization of these cells is essential. Expression of 12 stem cell marker genes in the canine prostate cancer cell line CT1258 and spheroid cells generated from these was analyzed by quantitative real-time PCR. In CT1258 and the generated spheroid cells, CD44 and CD133 expression was analyzed by flow cytometry, as well as proliferation and doxorubicin resistance. Integrin alpha-6 (ITGA6) expression and metabolic activity were significantly up-regulated in CT1258-derived spheroid cells, while doxorubicin resistance remained comparable. ITGA6 de-regulation and metabolic activity appear to be characteristic of the generated spheres, indicating potential intervention targets. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Choi, Hye Yeon; Kim, Seung Woo; Kim, BongWoo; Lee, Hae Na; Kim, Su-Jeong; Song, Minjung; Kim, Sol; Kim, Jungho; Kim, Young Bong; Kim, Jin-Hoi; Cho, Ssang-Goo
2014-01-01
Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE) increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol. PMID:24922551
França, Maria Eduarda Rocha de; Rocha, Sura Wanessa Santos; Oliveira, Wilma Helena; Santos, Laise Aline; de Oliveira, Anne Gabrielle Vasconcelos; Barbosa, Karla Patrícia Sousa; Nunes, Ana Karolina Santana; Rodrigues, Gabriel Barros; Lós, Deniele Bezerra; Peixoto, Christina Alves
2018-04-01
While diethylcarbamazine citrate (DEC) displays important anti-inflammatory effects in experimental models of liver injury, the mechanisms of its action remain poorly understood. The aim of the present study was to investigate the fibrolytic potential of DEC. Mice receive two injections of carbon tetrachloride (CCl 4 ) per week for 8 weeks. DEC 50 mg/kg body weight was administered through drinking water during the last 12 days of liver injury. The expression of hepatic stellate cells (HSCs) activation markers, including smooth muscle α-actin (α-SMA), collagen I, transforming growth factor-β 1 (TGF-β1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) was assessed. The influence of DEC on the intracellular MAPK pathways of the HSCs (JNK and p38 MAPK) was also estimated. DEC inhibited HSCs activation measured as the production of α-SMA and collagen I. In addition, it down regulated the production of TGF-β1 and TIMP-1, and concomitantly increased MMP-2 activity. Furthermore, DEC significantly inhibited the activation of the JNK and p38 MAPK signaling pathways. In conclusion, DEC significantly attenuated the severity of CCl 4 -induced liver injury and the progression of liver fibrosis, exerting a potential fibrolytic effect in the CCl 4 -induced fibrosis model.
Automated recognition of stratigraphic marker shales from geophysical logs in iron ore deposits
NASA Astrophysics Data System (ADS)
Silversides, Katherine; Melkumyan, Arman; Wyman, Derek; Hatherly, Peter
2015-04-01
The mining of stratiform ore deposits requires a means of determining the location of stratigraphic boundaries. A variety of geophysical logs may provide the required data but, in the case of banded iron formation hosted iron ore deposits in the Hamersley Ranges of Western Australia, only one geophysical log type (natural gamma) is collected for this purpose. The information from these logs is currently processed by slow manual interpretation. In this paper we present an alternative method of automatically identifying recurring stratigraphic markers in natural gamma logs from multiple drill holes. Our approach is demonstrated using natural gamma geophysical logs that contain features corresponding to the presence of stratigraphically important marker shales. The host stratigraphic sequence is highly consistent throughout the Hamersley and the marker shales can therefore be used to identify the stratigraphic location of the banded iron formation (BIF) or BIF hosted ore. The marker shales are identified using Gaussian Processes (GP) trained by either manual or active learning methods and the results are compared to the existing geological interpretation. The manual method involves the user selecting the signatures for improving the library, whereas the active learning method uses the measure of uncertainty provided by the GP to select specific examples for the user to consider for addition. The results demonstrate that both GP methods can identify a feature, but the active learning approach has several benefits over the manual method. These benefits include greater accuracy in the identified signatures, faster library building, and an objective approach for selecting signatures that includes the full range of signatures across a deposit in the library. When using the active learning method, it was found that the current manual interpretation could be replaced in 78.4% of the holes with an accuracy of 95.7%.
ERIC Educational Resources Information Center
Narita, Ritsuko
2009-01-01
The present study investigates the effectiveness of pragmatic consciousness-raising (PCR) activities in the L2 pragmatic acquisition of hearsay evidential markers by learners of Japanese as a foreign language (JFL). PCR is essentially an inductive approach to facilitating awareness of how language forms are used appropriately in a given context.…
Tong, Qi; Liu, Xu; Su, Feng; Quan, Fusheng; Guo, Zekun; Zhang, Yong
2013-01-01
Antibiotic selectable marker genes have been widely used to generate transgenic animals. Once transgenic animals have been obtained, the selectable marker is no longer necessary but raises public concerns regarding biological safety. The aim of this study was to prepare competent antibiotic selectable marker free transgenic cells for somatic cell nuclear transfer (SCNT). PhiC31 intergrase was used to insert a transgene cassette into a “safe harbor” in the bovine genome. Then, Cre recombinase was employed to excise the selectable marker under the monitoring of a fluorescent double reporter. By visually tracking the phenotypic switch from red to green fluorescence, antibiotic selectable marker free cells were easily detected and sorted by fluorescence-activated cell sorting. For safety, we used phiC31 mRNA and cell-permeant Cre protein in this study. When used as donor nuclei for SCNT, these safe harbor integrated marker-free transgenic cells supported a similar developmental competence of SCNT embryos compared with that of non-transgenic cells. After embryo transfer, antibiotic selectable marker free transgenic cattle were generated and anti-bacterial recombinant human β-defensin-3 in milk was detected during their lactation period. Thus, this approach offers a rapid and safe alternative to produce antibiotic selectable marker free transgenic farm animals, thereby making it a valuable tool to promote the healthy development and welfare of transgenic farm animals. PMID:23658729
Olas, Beata; Kedzierska, Magdalena; Wachowicz, Barbara; Stochmal, Anna; Oleszek, Wieslaw
2010-01-01
Bioactive substances found in numerous foods can be successfully and safely used to modify various cellular functions and affect the oxidative stress. Aronia melanocarpa fruits (Rosaceae) are one of the richest plant sources of phenolic substances shown to have anti-inflammatory, antitumor, antioxidative and antiplatelet activities. We investigated antioxidant properties of the extract from berries of A. melanocarpa by the estimation of the selected and other biomarkers of oxidative stress, i.e. the level of 8-epi-prostaglandin F(2) (8-EPI) (by immunoassay kit) and the amount of glutathione (by HPLC method) in control platelets and platelets treated with H(2)O(2). The expression of alpha(IIb)beta(3) (a marker of platelet activation) was measured by flow cytometer. The antioxidative and antiplatelet properties of the tested extract were also compared with the action of a well characterized antioxidative and antiplatelet commercial monomeric polyphenol-resveratrol. The extract from berries of A. melanocarpa (at the highest tested concentration -100 microg/ml) decreased the production of 8-EPI (a marker of lipid peroxidation) in control blood platelets and platelets treated with H(2)O(2) (2 mM). A combined action of the tested plant extract and H(2)O(2) evoked a significant increase of reduced form of glutathione in platelets compared with cells treated with H(2)O(2) only. Moreover, the tested plant extract (at the highest used concentration -100 microg/ml) reduced the expression of alpha(IIb)beta(3) on blood platelets. Comparative studies indicate that the tested plant extract was found to be more reactive in blood platelets than the solution of pure resveratrol.
Low intensity aerobic exercise and oxidative stress markers in older adults.
Bouzid, Mohamed A; Hammouda, Omar; Matran, Régis; Robin, Sophie; Fabre, Claudine
2014-10-01
This comparative study examined the effects of regular low intensity aerobic exercise on oxidative stress markers in older adults. The study was carried out on 15 sedentary subjects (age: 65.1 ± 3.5 years) versus 18 subjects performing fitness exercises (age: 65.8 ± 3.3 years). Before and after an incremental exercise test, oxidative stress markers were assessed. Superoxide dismutase was higher at rest and at the recovery for the physically active subjects compared with sedentary subjects (p < .05). At recovery, glutathione peroxidase and α -Tocopherol increased significantly above the resting values only in the active group (p < .05). Malondialdehyde had increased in both groups (p < .01), associated with a higher level in the sedentary group (p < .05) at the recovery. These data suggest that low intensity aerobic exercise may be useful to prevent the decline of antioxidants linked with aging.
Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D
2016-01-01
Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.
NASA Astrophysics Data System (ADS)
Broeg, Katja
2003-10-01
The activity of acid phosphatase in liver macrophage aggregates (MA-AP) of different fish species was used as a marker for a pollution-induced modulation of the digestive capacity of phagocytes, since functions of the non-specific immune response play a central role in the maintenance of animals' health. Based upon the investigation of more than 900 individual flounders (Platichthys flesus) and mullets (Liza aurata), natural variations, gender-specific differences and pollution-induced alterations in AP activity are demonstrated in this study. MA-AP activity was dependent on temperature and season but, nevertheless, distinctions between differently polluted areas were visible in all sampling campaigns with lowest MA-AP activity in fish from the polluted areas of the German Bight and the Israeli coast of the Mediterranean Sea. For organochlorine contaminants, as well as for mercury and copper, a significant correlation could be observed between residue concentrations in fish tissues and MA-AP activity. In all cases, except mercury which showed a positive correlation, AP activity was suppressed in animals with a high contaminant burden. MA-AP activity turned out to give reliable and consistent results for a quantification of immunomodulation in both fish species.
Intraovarian markers of follicular and oocyte maturation.
Pellicer, A; Diamond, M P; DeCherney, A H; Naftolin, F
1987-08-01
The use of ovulation induction for multiple follicular growth in in vitro fertilization (IVF) has introduced the problem of follicular asynchrony. As a consequence of the asynchrony, the parameters most commonly used by IVF groups to assess follicular and oocyte quality within those follicles are not sufficiently sensitive or specific. Thus, each follicle must be considered separately, and specific markers of follicular and/or oocyte maturation must be sought from within the follicle. In this review we analyze previous reports of potential markers of follicular and oocyte maturation. In regards to the follicular fluid constituents, the level of estradiol in follicular fluid correlates with fertilization and pregnancy in stimulated cycles. Other steroids are only helpful when specific stimulation protocols are used. The level of some follicular proteins such as alpha-1-antitrypsin and fibrinogen also correlates with fertilization and pregnancy outcome. Cyclic AMP levels in follicular fluid are significantly reduced in follicles leading to conception. Regulators of oocyte maturation, such as the Oocyte Maturation Inhibitor (OMI) or the Meiosis Inducing Substance (MIS) have also been correlated with IVF outcome, but their exact structure remains still unknown. In addition, other sophisticated parameters, such as chemotactic activity of human leukocytes, or simple methods, such as the presence of intrafollicular echoes, have also been used as successful markers in predicting IVF outcome.
The GCP molecular marker toolkit, an instrument for use in breeding food security crops.
Van Damme, Veerle; Gómez-Paniagua, Humberto; de Vicente, M Carmen
2011-12-01
Crop genetic resources carry variation useful for overcoming the challenges of modern agriculture. Molecular markers can facilitate the selection of agronomically important traits. The pervasiveness of genomics research has led to an overwhelming number of publications and databases, which are, nevertheless, scattered and hence often difficult for plant breeders to access, particularly those in developing countries. This situation separates them from developed countries, which have better endowed programs for developing varieties. To close this growing knowledge gap, we conducted an intensive literature review and consulted with more than 150 crop experts on the use of molecular markers in the breeding program of 19 food security crops. The result was a list of effectively used and highly reproducible sequence tagged site (STS), simple sequence repeat (SSR), single nucleotide polymorphism (SNP), and sequence characterized amplified region (SCAR) markers. However, only 12 food crops had molecular markers suitable for improvement. That is, marker-assisted selection is not yet used for Musa spp., coconut, lentils, millets, pigeonpea, sweet potato, and yam. For the other 12 crops, 214 molecular markers were found to be effectively used in association with 74 different traits. Results were compiled as the GCP Molecular Marker Toolkit, a free online tool that aims to promote the adoption of molecular approaches in breeding activities.
Chastin, Sebastien F. M.; Palarea-Albaladejo, Javier; Dontje, Manon L.; Skelton, Dawn A.
2015-01-01
The associations between time spent in sleep, sedentary behaviors (SB) and physical activity with health are usually studied without taking into account that time is finite during the day, so time spent in each of these behaviors are codependent. Therefore, little is known about the combined effect of time spent in sleep, SB and physical activity, that together constitute a composite whole, on obesity and cardio-metabolic health markers. Cross-sectional analysis of NHANES 2005–6 cycle on N = 1937 adults, was undertaken using a compositional analysis paradigm, which accounts for this intrinsic codependence. Time spent in SB, light intensity (LIPA) and moderate to vigorous activity (MVPA) was determined from accelerometry and combined with self-reported sleep time to obtain the 24 hour time budget composition. The distribution of time spent in sleep, SB, LIPA and MVPA is significantly associated with BMI, waist circumference, triglycerides, plasma glucose, plasma insulin (all p<0.001), and systolic (p<0.001) and diastolic blood pressure (p<0.003), but not HDL or LDL. Within the composition, the strongest positive effect is found for the proportion of time spent in MVPA. Strikingly, the effects of MVPA replacing another behavior and of MVPA being displaced by another behavior are asymmetric. For example, re-allocating 10 minutes of SB to MVPA was associated with a lower waist circumference by 0.001% but if 10 minutes of MVPA is displaced by SB this was associated with a 0.84% higher waist circumference. The proportion of time spent in LIPA and SB were detrimentally associated with obesity and cardiovascular disease markers, but the association with SB was stronger. For diabetes risk markers, replacing SB with LIPA was associated with more favorable outcomes. Time spent in MVPA is an important target for intervention and preventing transfer of time from LIPA to SB might lessen the negative effects of physical inactivity. PMID:26461112
Pal, Deeksha; Sharma, Ujjawal; Khajuria, Ragini; Singh, Shrawan Kumar; Kakkar, Nandita; Prasad, Rajendra
2015-05-15
In this study, we analyzed 100 cases of renal cell carcinoma (RCC) for telomerase activity, telomere length and alternative lengthening of telomeres (ALT) using the TRAP assay, TeloTTAGGG assay kit and immunohistochemical analysis of ALT associated promyelocytic leukemia (PML) bodies respectively. A significantly higher (P=0.000) telomerase activity was observed in 81 cases of RCC which was correlated with clinicopathological features of tumor for instance, stage (P=0.008) and grades (P=0.000) but not with the subtypes of RCC (P = 0.355). Notwithstanding, no correlation was found between telomerase activity and subtypes of RCC. Strikingly, the telomere length was found to be significantly shorter in RCC (P=0.000) to that of corresponding normal renal tissues and it is well correlated with grades (P=0.016) but not with stages (P=0.202) and subtypes (P=0.669) of RCC. In this study, telomere length was also negatively correlated with the age of patients (r(2)=0.528; P=0.000) which supports the notion that it could be used as a marker for biological aging. ALT associated PML bodies containing PML protein was found in telomerase negative cases of RCC. It suggests the presence of an ALT pathway mechanism to maintain the telomere length in telomerase negative RCC tissues which was associated with high stages of RCC, suggesting a prevalent mechanism for telomere maintenance in high stages. In conclusion, the telomerase activity and telomere length can be used as a diagnostic as well as a predictive marker in RCC. The prevalence of ALT mechanism in high stages of RCC is warranted for the development of anti-ALT inhibitors along with telomerase inhibitor against RCC as a therapeutic approach. Copyright © 2015 Elsevier B.V. All rights reserved.
Williams, Larry J; O'Boyle, Ernest H
2015-09-01
A persistent concern in the management and applied psychology literature is the effect of common method variance on observed relations among variables. Recent work (i.e., Richardson, Simmering, & Sturman, 2009) evaluated 3 analytical approaches to controlling for common method variance, including the confirmatory factor analysis (CFA) marker technique. Their findings indicated significant problems with this technique, especially with nonideal marker variables (those with theoretical relations with substantive variables). Based on their simulation results, Richardson et al. concluded that not correcting for method variance provides more accurate estimates than using the CFA marker technique. We reexamined the effects of using marker variables in a simulation study and found the degree of error in estimates of a substantive factor correlation was relatively small in most cases, and much smaller than error associated with making no correction. Further, in instances in which the error was large, the correlations between the marker and substantive scales were higher than that found in organizational research with marker variables. We conclude that in most practical settings, the CFA marker technique yields parameter estimates close to their true values, and the criticisms made by Richardson et al. are overstated. (c) 2015 APA, all rights reserved).
The Alcohol Dehydrogenase Isoenzyme as a Potential Marker of Pancreatitis.
Jelski, Wojciech; Piechota, Joanna; Orywal, Karolina; Szmitkowski, Maciej
2018-05-01
Human pancreas parenchyma contains various alcohol dehydrogenase (ADH) isoenzymes and also possesses aldehyde dehydrogenase (ALDH) activity. The altered activities of ADH and ALDH in damaged pancreatic tissue in the course of pancreatitis are reflected in the human serum. The aim of this study was to investigate a potential role of ADH and ALDH as markers for acute (AP) and chronic pancreatitis (CP). Serum samples were collected for routine biochemical investigations from 75 patients suffering from acute pancreatitis and 70 patients with chronic pancreatitis. Fluorometric methods were used to measure the activity of class I and II ADH and ALDH activity. The total ADH activity and activity of class III and IV isoenzymes were measured by a photometric method. There was a significant increase in the activity of ADH III isoenzyme (15.06 mU/l and 14.62 mU/l vs. 11.82 mU/l; p<0.001) and total ADH activity (764 mU/l and 735 mU/l vs. 568 mU/l) in the sera of patients with acute pancreatitis or chronic pancreatitis compared to the control. The diagnostic sensitivity for ADH III was about 84%, specificity was 92 %, positive and negative predictive values were 93% and 87% respectively in acute pancreatitis. Area under the Receiver Operating Curve (ROC) curve for ADH III in AP and CP was 0.88 and 0.86 respectively. ADH III has a potential role as a marker of acute and chronic pancreatitis. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Danielsen, Inge; Granström, Charlotta; Rytter, Dorte; Hammer Bech, Bodil; Brink Henriksen, Tine; Vaag, Allan Arthur; Olsen, Sjurdur Frodi
2013-08-01
It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring. Longitudinal study where 965 pregnant women during 1988-1989 had four dimensions of PA assessed by questionnaires in gestation week 30: PA at work; leisure time PA, daily amount of walking-biking and sport participation. The following MS markers were assessed in the offspring (n=439): body mass index (BMI), waist circumference, blood pressure, homeostasis model assessment insulin resistance as well as fasting plasma glucose, triglycerides, cholesterol (high-density lipoprotein (HDL), low-density lipoprotein and total cholesterol), insulin and leptin levels. Walking-biking PA in pregnancy is associated with unchanged or subtle, adverse changes of distinct MS markers among offspring including lower levels of HDL cholesterol (ratio 0.95 (95% CI 0.92 to 0.98) per 1 h increment in walking-biking), a higher diastolic blood pressure (difference 1.12 (95% CI 0.03 to 2.20) mm Hg/1 h increment) and a higher BMI (ratio 1.03 (95% CI 1.01 to 1.05) per 1 h increment). In separate analyses in males, these associations persisted and additional adverse associations were found for triglycerides, systolic blood pressure, waist circumference and leptin. No associations were detected with other measures of PA. The study did not substantiate any protective effects of PA in pregnancy. In contrast, data suggested that high amounts of daily walking-biking in pregnancy may have adverse effects on levels of HDL cholesterol, diastolic blood pressure and BMI in young adult offspring.
The Relations Between Immunity, Oxidative Stress and Inflammation Markers, in Childhood Obesity.
Laura Anca, Popescu; Bogdana, Virgolici; Olivia, Timnea; Horia, Virgolici; Dumitru, Oraseanu; Leon, Zagrean
2014-10-01
Oxidative stress, inflammation and insulin resistance are the principal culprits in childhood obesity. Immune modifications are also important in the development of the obesity complications.The aim of this study is to find the relations for some immunity parameters with markers for oxidative stress and inflammation. Sixty obese children (10-16 years old) and thirty age and sex matched lean children were involved. The activities for erythrocyte superoxid dismutase (SOD), for erythrocyte glutathione peroxidase (GPx) and serum thioredoxin level were measured by ELISA, as oxidative stress markers. Circulating immune complexes (CIC), complement fractions C3, C4 and the self-antibodies, antismooth muscle antibodies (ASMA), antiliver-kidney microsome antibodies (LKM1) were measured by ELISA methods. Ceruloplasmin, haptoglobin and C reactive protein (CRP) were measured as inflammatory markers by immunoturbidimetric methods. ceruloplasmin (p<0.001), haptoglobin (p<0.001), CRP (p<0.05) and activity for SOD (p<0.001) were measured, while thioredoxin concentration (p<0.04) was reduced. The antibodies LKM1 and ASMA and GPx activity were not modified between groups. Positive correlations (for p<0.05) were calculated between SOD activity and LKM1 (r=0.37), GPx activity and ASMA (r=0.27), haptoglobin and C3 (r=0.33), ceruloplasmin and CIC (r=0.41), CRP and C3 (p<0.27) and negative correlations were calculated for C4 both with GPx activity (r= -0.28) and with thioredoxin level (r= -0.27). In the obese children versus the lean ones, higher levels for C3 (p<0.001), C4(p<0.001), CIC (p<0.05), In conclusion, this study demonstrates that immune modifications, inflammation and oxidative stress are related and they act in cluster in childhood obesity. Copyright © 2014. Published by Elsevier Inc.
Abd Al Samid, May; Chaudhary, Belal; Khaled, Yazan S; Ammori, Basil J; Elkord, Eyad
2016-03-22
Regulatory T cells (Tregs) comprise numerous heterogeneous subsets with distinct phenotypic and functional features. Identifying Treg markers is critical to investigate the role and clinical impact of various Treg subsets in pathological settings, and also for developing more effective immunotherapies. We have recently shown that non-activated FoxP3-Helios+ and activated FoxP3+/-Helios+ CD4+ T cells express GARP/LAP immunosuppressive markers in healthy donors. In this study we report similar observations in the peripheral blood of patients with pancreatic cancer (PC) and liver metastases from colorectal cancer (LICRC). Comparing levels of different Treg subpopulations in cancer patients and controls, we report that in PC patients, and unlike LICRC patients, there was no increase in Treg levels as defined by FoxP3 and Helios. However, defining Tregs based on GARP/LAP expression showed that FoxP3-LAP+ Tregs in non-activated and activated settings, and FoxP3+Helios+GARP+LAP+ activated Tregs were significantly increased in both groups of patients, compared with controls. This work implies that a combination of Treg-specific markers could be used to more accurately determine expanded Treg subsets and to understand their contribution in cancer settings. Additionally, GARP-/+LAP+ CD4+ T cells made IL-10, and not IFN-γ, and levels of IL-10-secreting CD4+ T cells were elevated in LICRC patients, especially with higher tumor staging. Taken together, our results indicate that investigations of Treg levels in different cancers should consider diverse Treg-related markers such as GARP, LAP, Helios, and others and not only FoxP3 as a sole Treg-specific marker.
Eldecalcitol normalizes bone turnover markers regardless of their pre-treatment levels.
Shiraki, Masataka; Saito, Hitoshi; Matsumoto, Toshio
2012-09-01
Three-year treatment with eldecalcitol has been shown to improve lumbar and total hip bone mineral density (BMD), decrease bone turnover markers, and lower the incidences of vertebral and wrist fractures in patients with osteoporosis more than with treatment with alfacalcidol under vitamin D repletion. The purpose of this study was to determine whether there was a risk of eldecalcitol causing severely suppressed bone turnover in osteoporosis patients with low pre-treatment levels of bone turnover markers. Post-hoc analysis was conducted on the data from a 3-year, randomized, double-blind, active-comparator, clinical trial of eldecalcitol versus alfacalcidol under vitamin D repletion conducted in Japan. Enrolled patients with baseline measurements of bone turnover markers were stratified into tertiles according to their pre-treatment levels of serum bone-specific alkaline phosphatase, serum procollagen type I N-terminal propeptide, or urinary collagen-N-telopeptide. Eldecalcitol treatment rapidly reduced bone turnover markers, and kept them within the normal range. However, in the patients whose baseline values for bone turnover were low, eldecalcitol treatment did not further reduce bone turnover markers during the 3-year treatment period. Further long-term observation may be required to reach the conclusion. CLINICALTRIALS.GOV NUMBER: NCT00144456. Eldecalcitol normalizes, but does not overly suppress, bone turnover regardless of baseline levels of bone turnover markers. Thus, it is unlikely that eldecalcitol treatment will increase the risk of severely suppressed bone turnover and therefore deterioration of bone quality, at least for a treatment duration of 3 years.
Ramsay, Sheena; Lowe, Gordon D O; Whincup, Peter H; Rumley, Ann; Morris, Richard W; Wannamethee, S Goya
2008-04-01
Haemostatic and inflammatory markers have been hypothesised to mediate the relationship of social class and cardiovascular disease (CVD). We investigated whether a range of inflammatory/haemostatic markers are associated with social class independent of chronic diseases and behavioural risk factors in a population-based sample of 2682 British men aged 60-79 without a physician diagnosis of CVD, diabetes or musculoskeletal disease requiring anti-inflammatory medications. Men in lower social classes had higher mean levels of C-reactive protein, fibrinogen, interleukin-6, white blood cell count, von Willebrand factor (vWF), factor VIII, activated protein C (APC) resistance, plasma viscosity, fibrin D-dimer and platelet count, compared to higher social class groups; but not of tissue plasminogen activator antigen, haematocrit or activated partial prothrombin time. After adjustment for behavioural risk factors (smoking, alcohol, physical activity and body mass), the associations of social class with vWF, factor VIII, APC resistance, plasma viscosity, and platelet count though weakened, remained statistically significant, while those of other markers were considerably attenuated. In this study of older men without CVD, the social gradient in inflammatory and haemostatic markers was substantially explained by behavioural risk factors. The effect of socio-economic gradient on the factor VIII-vWF complex, APC resistance, plasma viscosity and platelet count merits further study.
Site of secretion of the trail marker of the eastern tent caterpillar.
Fitzgerald, T D; Edgerly, J S
1982-01-01
A new site of secretion of a chemical trail marker was found on the sternum at the tip of the last abdominal segment of the larva of the eastern tent caterpillarMalacosoma americanum. Larvae marked from this site by drawing their sterna along the substrate when they extended existing trails in search of food and again when they established recruitment trails to food-finds. Differences in the quantity or quality of the marker deposited by exploring and recruiting caterpillars may account for the greater activity of the recruitment trails.
Mucosal CCR1 gene expression as a marker of molecular activity in Crohn's disease: preliminary data.
Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Ţieranu, Eugen Nicolae; Popa, Caterina; Mănuc, Mircea; Preda, Carmen Monica; Ţieranu, Ioana; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel
2017-01-01
A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn's disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a panel of candidate genes in the mucosa from patients with active CD (CD-A), patients in remission (CD-R), and normal controls. Nine individuals were enrolled in the study: six CD patients (three with active lesions, three with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression levels of 84 genes previously associated with CD were evaluated by polymerase chain reaction (PCR) array. Ten genes out of 84 were found significantly differentially expressed in CD-A (CCL11, CCL25, DEFA5, GCG, IL17A, LCN2, REG1A, STAT3, MUC1, CCR1) and eight genes in CD-R (CASP1, IL23A, STAT1, STAT3, TNF, CCR1, CCL5, and HSP90B1) when compared to controls. A quantitative gene expression analysis revealed that CCR1 gene was more expressed in CD-A than in CD-R. Our data suggest that CCR1 gene may be a putative marker of molecular activity of Crohn's disease. Following these preliminary data, a confirmation in larger cohort studies could represent a useful method in order to identify new therapeutic targets.
Piotrowski, Wojciech J; Bieńkiewicz, Małgorzata; Frieske, Izabella; Marczak, Jerzy; Antczak, Adam; Górski, Paweł; Kuśmierek, Jacek; Płachcińska, Anna
2012-01-01
Discriminating between active and inactive sarcoidosis may be problematic in everyday clinical practice. There are numerous biochemical markers used in the diagnosis and monitoring of sarcoidosis. Somatostatin receptor (SR) scintigraphy with the use of 99mTc-octreotide may be used to estimate disease activity. The aim of the paper was to assess the value of traditional biomarkers (serum angiotensin-converting enzyme [SACE], C-reactive protein, markers of calcium metabolism, bronchoalveolar lavage fluid [BALF] lymphocytes) and a novel biomarker, 8-isoprostane (8-IP) in exhaled breath condensate (EBC), in the assessment of sarcoidosis activity in relation to somatostatin receptor scintigraphy. The study included 32 patients with sarcoidosis. Scintigraphy was performed using somatostatin analogue, 99mTc-HYNIC-TOC; planar and SPECT/CT images were recorded. The study group was divided into a subgroup with positive radiotracer uptake (n = 20) and without a visible uptake (n = 12). 8-IP levels were measured in EBC by an immunoenzymatic assay. RESULTS We observed a significantly higher EBC 8-IP levels in the subgroup with positive uptake compared with those with negative uptake (19.1 ± 19.8 vs. 5.4 ± 3.5 pg/ml, P = 0.02). The levels of SACE and the percentage of BALF lymphocytes were also nonsignificantly elevated. In the group of patients with positive scintigraphy results, a positive correlation was observed between the uptake ratio and SACE (r = 0.44, P = 0.041). The results indicate low value of biochemical markers in the assessment of disease activity. SR scintigraphy may have practical usefulness in the monitoring of sarcoidosis.
Calder, Philip C; Boobis, Alan; Braun, Deborah; Champ, Claire L; Dye, Louise; Einöther, Suzanne; Greyling, Arno; Matthys, Christophe; Putz, Peter; Wopereis, Suzan; Woodside, Jayne V; Antoine, Jean-Michel
2017-06-01
The conduct of high-quality nutrition research requires the selection of appropriate markers as outcomes, for example as indicators of food or nutrient intake, nutritional status, health status or disease risk. Such selection requires detailed knowledge of the markers, and consideration of the factors that may influence their measurement, other than the effects of nutritional change. A framework to guide selection of markers within nutrition research studies would be a valuable tool for researchers. A multidisciplinary Expert Group set out to test criteria designed to aid the evaluation of candidate markers for their usefulness in nutrition research and subsequently to develop a scoring system for markers. The proposed criteria were tested using thirteen markers selected from a broad range of nutrition research fields. The result of this testing was a modified list of criteria and a template for evaluating a potential marker against the criteria. Subsequently, a semi-quantitative system for scoring a marker and an associated template were developed. This system will enable the evaluation and comparison of different candidate markers within the same field of nutrition research in order to identify their relative usefulness. The ranking criteria of proven, strong, medium or low are likely to vary according to research setting, research field and the type of tool used to assess the marker and therefore the considerations for scoring need to be determined in a setting-, field- and tool-specific manner. A database of such markers, their interpretation and range of possible values would be valuable to nutrition researchers.
Akkurt, M; Çakır, A; Shidfar, M; Çelikkol, B P; Söylemezoğlu, G
2012-08-13
We used molecular markers associated with seedlessness in grapes, namely SCC8, SCF27 and VMC7f2, to improve the efficiency of seedless grapevine breeding via marker assisted selection (MAS). DNA from 372 F₁ hybrid progeny from the cross between seeded "Alphonse Lavallée" and seedless "Sultani" was amplified by PCR using three markers. After digestion of SCC8 marker amplification products by restriction enzyme BgIII, 40 individuals showed homozygous SCC8+/SCC8+ alleles at the seed development inhibitor (SdI) locus. DNA from 80 of the progeny amplified with the SCF27 marker produced bands; 174 individuals had 198-bp alleles of the VMC7f2 marker associated with seedlessness. In the second year, based on MAS, 183 F₁ hybrids were designated as seedless grapevine candidates because they were positive for a minimum of one marker. Twenty individuals were selected as genetic resources for future studies on seedless grapevine breeding because they carried alleles for the three markers associated with seedlessness. The VMC7f2 SSR marker was identified as the marker most associated with seedlessness.
Poremba, C; Hero, B; Goertz, H G; Scheel, C; Wai, D; Schaefer, K L; Christiansen, H; Berthold, F; Juergens, H; Boecker, W; Dockhorn-Dworniczak, B
2001-01-01
Neuroblastomas (NB) are a heterogeneous group of childhood tumours with a wide range of likelihood for tumour progression. As traditional parameters do not ensure completely accurate prognostic grouping, new molecular markers are needed for assessing the individual patient's prognosis more precisely. 133 NB of all stages were analysed in blind-trial fashion for telomerase activity (TA), expression of surviving, and MYCN status. These data were correlated with other traditional prognostic indicators and disease outcome. TA is a powerful independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative "favourable" clinical or biological subgroups of NB patients. High surviving expression is associated with an adverse outcome, but is more difficult to interprete than TA because survivin expression needs to be accurately quantified to be of predictive value. We propose an extended progression model for NB including emerging prognostic markers, with emphasis on telomerase activity.
Ipek, M; Seker, M; Ipek, A; Gul, M K
2015-03-31
The purpose of this study was to characterize olive core collection with amplified fragment length polymorphism (AFLP) markers and fruit traits and to determine AFLP markers significantly associated with these fruit characters in olive. A total of 168 polymorphic AFLP markers generated by five primer combinations and nine fruit traits were used to characterize relationships between 18 olive cultivars. Although all olive cultivars were discriminated from each other by either AFLP markers (<0.75 similarity level) or fruit traits, clustering based on the AFLP markers and fruit traits was not significantly correlated (r = 0.13). Partial clustering of olive cultivars by AFLP markers according to their geographical origin was observed. Associations of AFLP markers with fruits were determined using a multiple-regression analysis with stepwise addition of AFLP markers. Significant associations between eight AFLP markers and fruit traits were identified. While five AFLP markers demonstrated significant negative correlation with fruit and stone weight, width and length and total polyphenols (P < 0.05), three AFLP markers displayed significant positive correlation with α-tocopherol and γ-tocopherol (P < 0.01). This is the first report on the association of molecular markers with fruit traits in olive. Molecular markers associated with morphological and agronomic traits could be utilized for the breeding of olive cultivars. However, the association power of these markers needs to be confirmed in larger populations, and highly correlated markers should then be converted to PCR-based DNA markers such as sequence-characterized amplified region markers for better utilization.
Ultrafine particles generated from coloring with scented markers in the presence of ozone.
Fung, C-C D; Shu, S; Zhu, Y
2014-10-01
High concentrations of ultrafine particles (UFPs) have been previously reported during school art activities. This is possibly due to secondary organic aerosols (SOAs) formed from reactions between ozone and volatile organic compounds emitted from art products. Four brands of markers, three scented and one unscented, were tested inside a stainless steel chamber at eight different ozone concentrations between 0 and 300 ppb. Out of the 32 tested markers, only the lemon- and orange-scented markers from one brand reacted with ozone to form UFPs. Limonene, pinene, and several other terpenes were identified as ingredients of ink in SOA-forming markers. Coloring with one lemon-scented marker for 1 min without ozone generated on average approximately 26 ± 4 ppb of limonene inside the chamber. At 150 ppb ozone, using one lemon marker for 1 min formed on average 7.7 × 10(10) particles. The particle size distribution indicated an initial mode of 15 nm which grew to 40 nm. At 50 ppb ozone and below, no significant SOA formation occurred. The number of particles formed is moderately correlated with the mass of ink used (R(2) = 0.68). Based on these data, scented markers are not likely a strong source of SOA under normal indoor ozone levels. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Strahler, Jana; Fuchs, Reinhard; Nater, Urs M; Klaperski, Sandra
2016-06-01
Salivary cortisol (sCort) and alpha-amylase (sAA) are popular measurement tools for investigating hypothalamic-pituitary-adrenal and autonomic functioning, respectively. Despite their widespread use, only little is known about whether lifestyle factors such as regular exercise and physical fitness impact these two salivary stress markers. The lack of an objectively assessed fitness status is a major drawback of nearly all previous studies in this area. Our main objective was therefore to examine the impact of fitness status on sCort and sAA responses to a validated stressor. Sedentary to low-active men (N=115, 45.7±10.1 years, 26.7±3.4kg/m(2)) were exposed to the Trier Social Stress Test for Groups and provided saliva samples before and repeatedly after the stressor. An ergometer lactate exercise test provided information on physical fitness, that is, power achieved at the individual anaerobic threshold relative to body weight. From age-specific percentiles, a 2- (n=65 low fitness, n=50 high fitness) and a 3-group (n=37 low fitness, n=49 moderate fitness, n=29 high fitness) solution were calculated to elucidate the impact of different fitness levels. Prior to stress testing, sCort and sAA levels were similar in all groups. While both markers increased significantly due to stress exposure, fitness effects appeared rather small. When applying the 3-group solution, we observed attenuated sCort slopes in high- and moderate-fit men. Although sAA response slopes were pronounced in high-fit men, they failed to reach statistical significance. Mean stress reactivity (area under the curve with respect to ground, baseline, and response maximum) did not differ between groups and no association with fitness level was found. Our findings suggest only a weak effect of objectively assessed physical fitness on biological stress responses with attenuated hypothalamic-pituitary-adrenal but (non-significantly) higher autonomic responses in fitter men. Physical fitness is a factor
21 CFR 878.4660 - Skin marker.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Skin marker. 878.4660 Section 878.4660 Food and... GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4660 Skin marker. (a) Identification. A skin marker is a pen-like device intended to be used to write on the patient's skin, e.g., to outline surgical...
Qualitative Evaluation of Fiducial Markers for Radiotherapy Imaging
Chan, Maria F.; Cohen, Gil’ad N.; Deasy, Joseph O.
2016-01-01
Purpose To evaluate visibility, artifacts, and distortions of various commercial markers in magnetic resonance imaging (MRI), computer tomography (CT), and ultrasound imaging used for radiotherapy planning and treatment guidance. Methods We compare 2 solid gold markers, 4 gold coils, and 1 polymer marker from 3 vendors. Imaging modalities used were 3-T and 1.5-T GE MRIs, Siemens Sequoia 512 Ultrasound, Phillips Big Bore CT, Varian Trilogy linear accelerator (cone-beam CT [CBCT], on-board imager kilovoltage [OBI-kV], electronic portal imaging device megavoltage [EPID-MV]), and Medtronic O-ARM CBCT. Markers were imaged in a 30 × 30 × 10 cm3 custom bolus phantom. In one experiment, Surgilube was used around the markers to reduce air gaps. Images were saved in Digital Imaging and Communications in Medicine (DICOM) format and analyzed using an in-house software. Profiles across the markers were used for objective comparison of the markers’ signals. The visibility and artifacts/distortions produced by each marker were assessed qualitatively and quantitatively. Results All markers are visible in CT, CBCT, OBI-kV, and ultrasound. Gold markers below 0.75 mm in diameter are not visible in EPID-MV images. The larger the markers, the more CT and CBCT image artifacts there are, yet the degree of the artifact depends on scan parameters and the scanner itself. Visibility of gold coils of 0.75 mm diameter or larger is comparable across all imaging modalities studied. The polymer marker causes minimal artifacts in CT and CBCT but has poor visibility in EPID-MV. Gold coils of 0.5 mm exhibit poor visibility in MRI and EPID-MV due to their small size. Gold markers are more visible in 3-T T1 gradient-recalled echo than in 1.5-T T1 fast spin-echo, depending on the scan sequence. In this study, all markers are clearly visible on ultrasound. Conclusion All gold markers are visible in CT, CBCT, kV, and ultrasound; however, only the large diameter markers are visible in MV. When MR and
Imaging markers for Alzheimer disease
Bocchetta, Martina; Chételat, Gael; Rabinovici, Gil D.; de Leon, Mony J.; Kaye, Jeffrey; Reiman, Eric M.; Scheltens, Philip; Barkhof, Frederik; Black, Sandra E.; Brooks, David J.; Carrillo, Maria C.; Fox, Nick C.; Herholz, Karl; Nordberg, Agneta; Jack, Clifford R.; Jagust, William J.; Johnson, Keith A.; Rowe, Christopher C.; Sperling, Reisa A.; Thies, William; Wahlund, Lars-Olof; Weiner, Michael W.; Pasqualetti, Patrizio; DeCarli, Charles
2013-01-01
Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on which marker (i.e., amyloid imaging, 18F-fluorodeoxyglucose [FDG]-PET, SPECT, MRI) as well as how it is measured (“metric”: visual, manual, semiautomated, or automated segmentation/computation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR+ (LR−), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR+ of markers was between 4.4 and 9.4 and LR− between 0.25 and 0.08, whereas prognostic LR+ and LR− were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR+ from approximately 1 to 100; LR− from approximately 1.00 to 0.01. Markers accounted for 11% and 18% of diagnostic and prognostic variance of LR+ and 16% and 24% of LR−. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13% and 62% of diagnostic and prognostic variance of LR+, and 29% and 18% of LR−. Within markers, the largest proportion of diagnostic LR+ and LR− variability was within 18F-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials. PMID:23897875
Delessert, Alexandre; Espa, Fabrice; Rossetti, Andrea; Lavigne, Gilles; Tafti, Mehdi; Heinzer, Raphael
2010-01-01
Background: During sleep, sudden drops in pulse wave amplitude (PWA) measured by pulse oximetry are commonly associated with simultaneous arousals and are thought to result from autonomic vasoconstriction. In the present study, we determine whether PWA drops were associated with changes in cortical activity as determined by EEG spectral analysis. Methods: A 20% decrease in PWA was chosen as a minimum for a drop. A total of 1085 PWA drops from 10 consecutive sleep recordings were analyzed. EEG spectral analysis was performed over 5 consecutive epochs of 5 seconds: 2 before, 1 during, and 2 after the PWA drop. EEG spectral analysis was performed over delta, theta, alpha, sigma, and beta frequency bands. Within each frequency band, power density was compared across the five 5-sec epochs. Presence or absence of visually scored EEG arousals were adjudicated by an investigator blinded to the PWA signal and considered associated with PWA drop if concomitant. Results: A significant increase in EEG power density in all EEG frequency bands was found during PWA drops (P < 0.001) compared to before and after drop. Even in the absence of visually scored arousals, PWA drops were associated with a significant increase in EEG power density (P < 0.001) in most frequency bands. Conclusions: Drops in PWA are associated with a significant increase in EEG power density, suggesting that these events can be used as a surrogate for changes in cortical activity during sleep. This approach may prove of value in scoring respiratory events on limited-channel (type III) portable monitors. Citation: Delessert A; Espa F; Rossetti A; Lavigne G; Tafti M; Heinzer R. Pulse wave amplitude drops during sleep are reliable surrogate markers of changes in cortical activity. SLEEP 2010;33(12):1687-1692. PMID:21120131
Diniz, Breno Satler; Talib, Leda Leme; Joaquim, Helena Passarelli Giroud; de Paula, Vanessa Rodrigues Jesus; Gattaz, Wagner Farid; Forlenza, Orestes Vicente
2011-04-01
Increased GSK3B activity has been reported as a state marker of major affective episodes in patients with depression and bipolar disorder. No study so far has addressed GSK3B activity in late-life depression. The aims of the present study were to determine GSK3B activity in platelets of elderly patients with major depression, and the association between GSK3B activity and the severity of depressive symptoms and cognitive impairment. Forty drug-free elderly patients with major depressive episode were compared to healthy older adults (n = 13). Severity of the depressive episode and current cognitive state were determined by the Hamilton Depression Scale (HAM-D) and the Cambridge Cognitive Test (CAMCOG), respectively. Total- and ser-9-phosphorylated GSK3B (tGSK3B and pGSK3B) were determined in platelets by enzyme immunometric assays (EIA). GSK3B activity was indirectly inferred by the GSK3B ratio (i.e. pGSK3B/tGSK3B). Elderly depressed patients had significantly lower pGSK3B levels (P = 0.03) and GSK3B ratio (P = 0.03), indicating higher GSK3B activity. Higher GSK3B activity were observed in patients with severe depressive episode (HAM-D scores >22, P = 0.03) and with cognitive impairment (CAMCOG scores <86, P = 0.01). The present findings provide additional evidence of the involvement of GSK3B in the pathophysiology of late-life major depression. Higher GSK3B activity may be more relevant in those patients with more severe depressive symptoms and cognitive impairment.
Constantinescu, R; Krýsl, D; Bergquist, F; Andrén, K; Malmeström, C; Asztély, F; Axelsson, M; Menachem, E B; Blennow, K; Rosengren, L; Zetterberg, H
2016-04-01
Clinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. Demographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 ± 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability. © 2016 EAN.
2014-01-01
Background Although the X chromosome is the second largest bovine chromosome, markers on the X chromosome are not used for genomic prediction in some countries and populations. In this study, we presented a method for computing genomic relationships using X chromosome markers, investigated the accuracy of imputation from a low density (7K) to the 54K SNP (single nucleotide polymorphism) panel, and compared the accuracy of genomic prediction with and without using X chromosome markers. Methods The impact of considering X chromosome markers on prediction accuracy was assessed using data from Nordic Holstein bulls and different sets of SNPs: (a) the 54K SNPs for reference and test animals, (b) SNPs imputed from the 7K to the 54K SNP panel for test animals, (c) SNPs imputed from the 7K to the 54K panel for half of the reference animals, and (d) the 7K SNP panel for all animals. Beagle and Findhap were used for imputation. GBLUP (genomic best linear unbiased prediction) models with or without X chromosome markers and with or without a residual polygenic effect were used to predict genomic breeding values for 15 traits. Results Averaged over the two imputation datasets, correlation coefficients between imputed and true genotypes for autosomal markers, pseudo-autosomal markers, and X-specific markers were 0.971, 0.831 and 0.935 when using Findhap, and 0.983, 0.856 and 0.937 when using Beagle. Estimated reliabilities of genomic predictions based on the imputed datasets using Findhap or Beagle were very close to those using the real 54K data. Genomic prediction using all markers gave slightly higher reliabilities than predictions without X chromosome markers. Based on our data which included only bulls, using a G matrix that accounted for sex-linked relationships did not improve prediction, compared with a G matrix that did not account for sex-linked relationships. A model that included a polygenic effect did not recover the loss of prediction accuracy from exclusion of X
Luo, Zhijing; Chen, Mingjiao; Zhao, Xiangxiang; Zhang, Dabing; Qi, Yiping; Yuan, Zheng
2016-01-01
Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection. PMID:26799713
Fan, Wei; Zong, Jie; Luo, Zhijing; Chen, Mingjiao; Zhao, Xiangxiang; Zhang, Dabing; Qi, Yiping; Yuan, Zheng
2016-01-01
Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection.
Biochemical markers in the assessment of bone disease
NASA Technical Reports Server (NTRS)
Bikle, D. D.
1997-01-01
As the mean age of our population increases, increasing attention has been paid to the diseases associated with aging, including diseases of the skeleton such as osteoporosis. Effective means of treating and possibly preventing such skeletal disorders are emerging, making their early recognition an important goal for the primary care physician. Although bone density measurements and skeletal imaging studies remain of primary diagnostic importance in this regard, a large number of assays for biochemical markers of bone formation and resorption are being developed that promise to complement the densitometry measurements and imaging studies, providing an assessment of the rates of bone turnover and an earlier evaluation of the effects of therapy. In this review, emphasizing the recent literature, the major biochemical markers currently in use or under active investigation are described, and their application in a number of diseases of the skeleton including osteoporosis is evaluated.
Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David
2017-01-01
Objective The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. Methods In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Results Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3+ CD56− T lymphocytes, CD3+ CD56+ NKT cells, CD3−CD56+ NK cells, and also some cells within the CD3−CD56− non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. Conclusion The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls
Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David
2017-01-01
The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3 + CD56 - T lymphocytes, CD3 + CD56 + NKT cells, CD3 - CD56 + NK cells, and also some cells within the CD3 - CD56 - non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls from live B. coagulans GBI-30, 6086
Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C
2011-11-01
Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normal<100), but extended antibody testing, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2), was negative. The patient showed a partial response to steroid treatment, which was started late in the disease course. On review at 13 months of age, her development was consistent with an age of 5 to 6 months. These results suggest that VGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.
Machiels, Melanie; van Hooft, Jeanin; Jin, Peng; van Berge Henegouwen, Mark I; van Laarhoven, Hanneke M; Alderliesten, Tanja; Hulshof, Maarten C
2015-10-01
Markers placed at the borders of esophageal tumors are potentially useful to facilitate radiotherapy (RT) target delineation, which offers the possibility of image-guided RT. To evaluate and compare the feasibility and technical benefit of endoscopy/EUS-guided marker placement of 3 different types of markers in patients with esophageal cancer referred for RT. Prospective, single-center, feasibility and comparative study. Tertiary-care medical center. Thirty patients with esophageal cancer who were referred for RT. Patients underwent endoscopy/EUS-guided implantation of 1 type of marker. A solid gold marker (SM) with fixed dimensions, a flexible coil-shaped gold marker (FM) with hand-cut length (2-10 mm), and a radiopaque hydrogel marker (HG) were used. Technical feasibility and adverse events were registered. CT scans and cone-beam CT scans (CBCT) acquired during RT were analyzed to determine and compare the visibility and continuous clear visibility of the implanted markers. Technical feasibility, technical benefit, and adverse events of 3 types of markers. A total of 101 markers were placed in 30 patients. Implantation was technically feasible in all patients without grade 3 to 4 adverse events. Two patients with asymptomatic mediastinitis and one with asymptomatic pneumothorax were seen. Visibility on CT scan of all 3 types of implanted markers was adequate for target delineation. Eighty percent of FMs remained continuously visible over the treatment period on CBCT, significantly better than SMs (63%) and HGs (11%) (P = .015). When we selected FMs ≥5 mm, 90.5% remained visible on CBCT between implantation and the end of RT. Single-center, nonrandomized design. Endoscopy/EUS-guided fiducial marker placement for esophageal cancer is both safe and feasible and can be used for target volume delineation purposes on CT. Our results imply a significant advantage of FMs over SMs and HGs, regarding visibility and continuous clear visibility over the treatment period
Evaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease.
Awoniyi, Dolapo O; Teuchert, Andrea; Sutherland, Jayne S; Mayanja-Kizza, Harriet; Howe, Rawleigh; Mihret, Adane; Loxton, Andre G; Sheehama, Jacob; Kassa, Desta; Crampin, Amelia C; Dockrell, Hazel M; Kidd, Martin; Rosenkrands, Ida; Geluk, Annemieke; Ottenhoff, Tom H M; Corstjens, P L A M; Chegou, Novel N; Walzl, Gerhard
2016-09-01
We investigated the accuracy of host markers detected in Mtb antigen-stimulated whole blood culture supernatant in the diagnosis of TB. Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24 h whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques. 17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients. A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Evaluation of solar-powered raised pavement markers.
DOT National Transportation Integrated Search
2008-01-01
An evaluation of a limited number of solar-powered raised pavement markers (SRPMs) was conducted to : determine if this type of marker would be more visible than retroreflective markers in some situations on : Oregon highways. SRPMs typically use Lig...
A SOMATIC-MARKER THEORY OF ADDICTION
Verdejo-García, Antonio; Bechara, Antoine
2009-01-01
Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance abusers show altered decision-making, characterized by a tendency to choose the immediate reward, at the expense of negative future consequences. The somatic-marker model proposes that decision-making depends on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between alterations in processing emotions in substance abusers, and their impairments in decision-making. A growing evidence from neuroscientific studies indicate that core aspects of addiction may be explained in terms of abnormal emotional/homeostatic guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in substance abusers. Neuroimaging studies have shown that altered decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, and the experience of “craving”, including the VMPC, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker theory of addiction. We conclude that there are at least two underlying types of dysfunctions where emotional signals (somatic-markers) turns in favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a given action. PMID:18722390
NASA Astrophysics Data System (ADS)
Arnold, Thomas; De Biasio, Martin; Leitner, Raimund
2015-06-01
Two problems are addressed in this paper (i) the fluorescent marker-based and the (ii) marker-free discrimination between healthy and cancerous human tissues. For both applications the performance of hyper-spectral methods are quantified. Fluorescent marker-based tissue classification uses a number of fluorescent markers to dye specific parts of a human cell. The challenge is that the emission spectra of the fluorescent dyes overlap considerably. They are, furthermore disturbed by the inherent auto-fluorescence of human tissue. This results in ambiguities and decreased image contrast causing difficulties for the treatment decision. The higher spectral resolution introduced by tunable-filter-based spectral imaging in combination with spectral unmixing techniques results in an improvement of the image contrast and therefore more reliable information for the physician to choose the treatment decision. Marker-free tissue classification is based solely on the subtle spectral features of human tissue without the use of artificial markers. The challenge in this case is that the spectral differences between healthy and cancerous tissues are subtle and embedded in intra- and inter-patient variations of these features. The contributions of this paper are (i) the evaluation of hyper-spectral imaging in combination with spectral unmixing techniques for fluorescence marker-based tissue classification, (ii) the evaluation of spectral imaging for marker-free intra surgery tissue classification. Within this paper, we consider real hyper-spectral fluorescence and endoscopy data sets to emphasize the practical capability of the proposed methods. It is shown that the combination of spectral imaging with multivariate statistical methods can improve the sensitivity and specificity of the detection and the staging of cancerous tissues compared to standard procedures.
Oxidative stress markers imbalance in late-life depression.
Diniz, Breno S; Mendes-Silva, Ana Paula; Silva, Lucelia Barroso; Bertola, Laiss; Vieira, Monica Costa; Ferreira, Jessica Diniz; Nicolau, Mariana; Bristot, Giovana; da Rosa, Eduarda Dias; Teixeira, Antonio L; Kapczinski, Flavio
2018-03-20
Oxidative stress has been implicated in the pathophysiology of mood disorders in young adults. However, there is few data to support its role in the elderly. The primary aim of this study was to evaluate whether subjects with late-life depression (LLD) presented with changes in oxidative stress response in comparison with the non-depressed control group. We then explored how oxidative stress markers associated with specific features of LLD, in particular cognitive performance and age of onset of major depressive disorder in these individuals. We included a convenience sample of 124 individuals, 77 with LLD and 47 non-depressed subjects (Controls). We measure the plasma levels of 6 oxidative stress markers: thiobarbituric acid reactive substances (TBARS), protein carbonil content (PCC), free 8-isoprostane, glutathione peroxidase (GPx) activity, glutathione reductase (GR) activity, and glutathione S-transferase (GST) activity. We found that participants with LLD had significantly higher free 8-isoprostane levels (p = 0.003) and lower glutathione peroxidase activity (p = 0.006) compared to controls. Free 8-isoprostane levels were also significantly correlated with worse scores in the initiation/perseverance (r = -0.24, p = 0.01), conceptualization (r = -0.22, p = 0.02) sub-scores, and the total scores (r = -0.21, p = 0.04) on the DRS. Our study provides robust evidence of the imbalance between oxidative stress damage, in particular lipid peroxidation, and anti-oxidative defenses as a mechanism related to LLD, and cognitive impairment in this population. Interventions aiming to reduce oxidative stress damage can have a potential neuroprotective effect for LLD subjects. Copyright © 2018 Elsevier Ltd. All rights reserved.
De Vito, Rita; Alisi, Anna; Masotti, Andrea; Ceccarelli, Sara; Panera, Nadia; Citti, Arianna; Salata, Michele; Valenti, Luca; Feldstein, Ariel E; Nobili, Valerio
2012-07-01
Concomitantly to the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in children. NAFLD encompasses a spectrum of histological damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with possible progression to cirrhosis. There is growing evidence that the immune system plays a pivotal role in the initiation and progression to NASH but the cellular nature of the hepatic inflammation is still unknown. The present study includes 34 children with biopsy-proven NAFLD. Liver damage was evaluated by the NAFLD activity score (NAS), and the inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3 and CD163 which are markers of leukocytes, T cells and activated Kupffer cells/macrophages, respectively. Our results have shown that CD45+ (P<0.0001) and CD163+ (P<0.0001) cells were markedly increased in children with severe histological activity (NAS≥5) compared to children with lower activity (NAS<5), whereas CD3+ cells were significantly lower (P<0.01) in children with severe histological activity. There was a significant association between the numbers of CD45+, CD3+ and CD163+ cells, regarding both the portal tract and liver lobule, and the severity of steatosis, ballooning and fibrosis (P<0.01). These data suggest that the severity and composition of the inflammatory infiltrate correlate with steatosis and the severity of disease in children with NAFLD. Moreover, a decrease in CD3+ cells may be involved in the pathogenesis of liver damage. Future studies should evaluate whether it can predict the progression of liver disease independently of established histological scores.
Fujita, Yukihiro; Hara, Yasushi; Nezu, Yoshinori; Yamaguchi, Shinya; Schulz, Kurt S; Tagawa, Masahiro
2005-12-01
To compare activities of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and matrix metalloproteinase (MMP)-3 and contents of sulfated glycosaminoglycan (S-GAG) in joint fluid obtained from dogs with hip dysplasia (HD) and clinically normal dogs, evaluate correlations among these markers in joint fluid obtained from dogs with HD, and evaluate correlations between each marker and clinical and radiographic variables. Animals-26 dogs with HD (clinical group) and 43 clinically normal Beagles (control group). Joint fluid was aseptically collected from the hip joints of all dogs. For each dog in the clinical group, age, duration of lameness, radiographic osteoarthritis (OA) score, and Norberg angle in each affected joint were recorded. Activities of IL-1beta, IL-6, TNF-alpha, and MMP-3 and S-GAG contents were measured. Values were compared between groups by use of Mann-Whitney U tests, and the Spearman rank correlation test was used to evaluate correlations among markers and between each marker and clinical or radiographic variables. Values of all markers were significantly higher for the clinical group, compared with values for the control group. There was a moderate positive correlation between lameness duration and IL-6 activity and a strong negative correlation between the Norberg angle and IL-1beta activity. Analysis of our results indicated that there was a significant increase in markers of OA in dogs with HD. Activities of IL-1beta and IL-6 in joint fluid of dogs with HD may be influenced by the severity of laxity in the hip joint and lameness duration, respectively.
Naqvi, Arshi; Malasoni, Richa; Gupta, Swati; Srivastava, Akansha; Pandey, Rishi R; Dwivedi, Anil Kumar
2017-10-01
Turmeric ( Curcuma longa ) is reported to possess wide array of biological activities. Herbal Medicament (HM) is a standardized hexane-soluble fraction of C. longa and is well known for its neuroprotective effect. In this study, we attempted to synthesize a novel chemically modified bioactive fraction from HM (NCCL) along with isolation and characterization of a novel marker compound (I). NCCL was prepared from HM. The chemical structure of the marker compound isolated from NCCL was determined from 1D/2D nuclear magnetic resonance, mass spectroscopy, and Fourier transform infrared. The compound so isolated was subjected to in silico and in vitro screenings to test its inhibitory effect on estrogen receptors. Molecular docking studies revealed that the binding poses of the compound I was energetically favorable. Among NCCL and compound I taken for in vitro studies, NCCL had exhibited good anti-cancer activity over compound I against MCF-7, MDA-MB-231, DU-145, and PC-3 cells. This is the first study about the synthesis of a chemically modified bioactive fraction which used a standardized extract since the preparation of the HM. It may be concluded that NCCL fraction having residual components induce more cell death than compound I alone. Thus, NCCL may be used as a potent therapeutic drug. In the present paper, a standardized hexane soluble fraction of Curcuma longa (HM) was chemically modified to give a novel bioactive fraction (NCCL). A novel marker compound was isolated from NCCL and was characerized using various spectral techniques. The compound so isolated was investigated for in-silico screenings. NCCL and isolated compound was subjected to in-vitro anti-cancer screenings against MCF 7, MDA MB 231 (breast adenocarcinoma) and DU 145 and PC 3 cell lines (androgen independent human prostate cancer cells). The virtual screenings reveals that isolated compound has shown favourable drug like properties. NCCL fraction having residual components induces more cell
Sequencing consolidates molecular markers with plant breeding practice.
Yang, Huaan; Li, Chengdao; Lam, Hon-Ming; Clements, Jonathan; Yan, Guijun; Zhao, Shancen
2015-05-01
Plenty of molecular markers have been developed by contemporary sequencing technologies, whereas few of them are successfully applied in breeding, thus we present a review on how sequencing can facilitate marker-assisted selection in plant breeding. The growing global population and shrinking arable land area require efficient plant breeding. Novel strategies assisted by certain markers have proven effective for genetic gains. Fortunately, cutting-edge sequencing technologies bring us a deluge of genomes and genetic variations, enlightening the potential of marker development. However, a large gap still exists between the potential of molecular markers and actual plant breeding practices. In this review, we discuss marker-assisted breeding from a historical perspective, describe the road from crop sequencing to breeding, and highlight how sequencing facilitates the application of markers in breeding practice.
Metabolic muscle damage and oxidative stress markers in an America's Cup yachting crew.
Barrios, Carlos; Hadala, Michal; Almansa, Inmaculada; Bosch-Morell, Francisco; Palanca, José M; Romero, Francisco J
2011-07-01
Activities of enzymes involved in muscle damage [creatine kinase (CK) and aspartate aminotransferase (AST)] and levels of malondialdehyde (MDA) as a marker of oxidative stress were monitored in the plasma of 27 members of an America's Cup yachting crew. The preventive benefits of allopurinol on muscle damage were also tested. In racing period A, the crew was divided into two groups according to their tasks on board. Blood samples from all 27 sailors were obtained before the start of a 5-day fleet race, after the last race, and after the ten match races. In period B, crew members were divided at random into two groups. One group (13 participants) received 300 mg/day of allopurinol 3 h before racing. The other ten members received placebo. Blood samples were collected just before and after the second round of the Louis Vuitton Cup. All participants showed increased CK and AST activities after the racing period A. The increase in CK activity was highest in sailors involved in strenuous physical work. At the end of period A, plasma MDA levels were higher in all participants as compared with non-participant athletes. In period B, a significant decrease in CK activity, but not in AST, appeared among participants receiving allopurinol. Plasma MDA decreased in sailors treated with allopurinol, but this reduction did not reach statistical significance. America's Cup is a sailing sport with high physical demands, as shown by the increase in muscle-damage markers. Treatment with allopurinol appeared to decrease the levels of muscle damage markers.
L-split marker for augmented reality in aircraft assembly
NASA Astrophysics Data System (ADS)
Han, Pengfei; Zhao, Gang
2016-04-01
In order to improve the performance of conventional square markers widely used by marker-based augmented reality systems in aircraft assembly environments, an L-split marker is proposed. Every marker consists of four separate L-shaped parts and each of them contains partial information about the marker. Geometric features of the L-shape, which are more discriminate than the symmetrical square shape adopted by conventional markers, are used to detect proposed markers from the camera images effectively. The marker is split into four separate parts in order to improve the robustness to occlusion and curvature to some extent. The registration process can be successfully completed as long as three parts are detected (up to about 80% of the area could be occluded). Moreover, when we attach the marker on nonplanar surfaces, the curvature status of the marker can be roughly analyzed with every part's normal direction, which can be obtained since their six corners have been explicitly determined in the previous detection process. And based on the marker design, new detection and recognition algorithms are proposed and detailed. The experimental results show that the marker and the algorithms are effective.
Oxidative stress markers during a course of hyperthyroidism.
Lampka, Magdalena; Junik, Roman; Nowicka, Anna; Kopczyńska, Ewa; Tyrakowski, Tomasz; Odrowaz-Sypniewska, Grazyna
2006-01-01
Previous studies have shown the presence of oxidative stress in hyperthyroid patients. The aim of this study was to evaluate the influence of hyperthyroidism on lipid peroxidation, plasma lipoprotein oxidation and antioxidant status. We have estimated the clinical utility of the biochemical parameters analysed as markers of oxidative stress in hyperthyroidism. Twenty five patients with overt hyperthyroidism because of Graves' disease or toxic multinodular goitre and 20 healthy subjects were included in the study. Lipid peroxidation was evaluated by measurement of peroxides and malondialdehyde with 4-hydroxynonenal (MDA + 4-HNE) concentrations. Autoantibodies against oxidised LDL (anti-oxLDL) were assayed as a marker of lipoprotein oxidation. Changes in the antioxidant defence system were estimated by measurement of total antioxidant status in serum (TAS) and erythrocyte superoxide dismutase activity (SOD). A significant increase in serum concentration of peroxides and MDA + 4-HNE was observed in patients with hyperthyroidism. However, no difference was found in anti-oxLDL concentration and antioxidant status parameters (TAS, SOD) between the control group and the patient group. Our results indicate an intensification of the oxidative processes caused by an excess of thyroid hormones, which is not accompanied by a response from the antioxidant system. Elevated concentrations of lipid peroxidation products in serum, both peroxides and malondialdehyde with 4-hydroxynonenal, may be useful as markers of oxidative stress during the course of hyperthyroidism.
Tumour markers in diagnosis and management.
Warnes, T W; Smith, A
1987-01-01
The 20-year period since the discovery of AFP by Abelev has seen the introduction of a wide range of new tumour markers and it is now clear that PLC is biologically heterogeneous. Hepatoblastomas, fibrolamellar carcinomas, hepatocellular carcinomas and cholangiocarcinomas may secrete a variety of distinctive markers which are predominantly glycoproteins, and may resemble those found in placenta or fetal liver. Diagnostically, AFP remains the best marker for HCC, both in sensitivity and specificity; it is known to consist of isoforms. In patients with elevated serum AFP and filling defects on liver scan, Con A reactive AFP may differentiate PLC from hepatic metastases, whilst fucosylated AFP may distinguish PLC from benign disorders when AFP is non-diagnostically elevated. With this recognition of tumour heterogeneity the value of a multiple-marker approach has become apparent. The measurement of vitamin B12 binding protein and neurotensin should lead to the detection of most patients with the fibrolamellar variant of HCC and many of these should be resectable. In patients with normal serum AFP levels, HCC-associated GGTP is of major value whilst in low-incidence areas for HCC, patients should also be screened for H-ALP; using a multiple marker approach in high-risk groups, 90% of clinically diagnosed hepatocellular carcinomas are serologically positive. The Chinese and Alaskan studies, in which small, potentially resectable tumours were detected, suggest that it is now possible to achieve 5-year survival figures of up to 60% in HCC patients detected by screening. The value of such a strategy in low-incidence countries is currently under study. In patient monitoring, as in diagnosis, AFP remains the outstanding marker. In AFP-negative patients, other markers including vitamin B12-binding protein, neurotensin, HCC-specific isoenzymes, des-gamma-carboxy-prothrombin and alpha-fucosidase, are of undoubted diagnostic value, but their value as indicants of disease
The Effects of Caffeine on Sleep and Maturational Markers in the Rat
Olini, Nadja; Kurth, Salomé; Huber, Reto
2013-01-01
Adolescence is a critical period for brain maturation during which a massive reorganization of cortical connectivity takes place. In humans, slow wave activity (<4.5 Hz) during NREM sleep was proposed to reflect cortical maturation which relies on use-dependent processes. A stimulant like caffeine, whose consumption has recently increased especially in adolescents, is known to affect sleep wake regulation. The goal of this study was to establish a rat model allowing to assess the relationship between cortical maturation and sleep and to further investigate how these parameters are affected by caffeine consumption. To do so, we assessed sleep and markers of maturation by electrophysiological recordings, behavioral and structural readouts in the juvenile rat. Our results show that sleep slow wave activity follows a similar inverted U-shape trajectory as already known in humans. Caffeine treatment exerted short-term stimulating effects and altered the trajectory of slow wave activity. Moreover, caffeine affected behavioral and structural markers of maturation. Thus, caffeine consumption during a critical developmental period shows long lasting effects on sleep and brain maturation. PMID:24023748
Shvil, Erel; Rusch, Heather L; Sullivan, Gregory M; Neria, Yuval
2013-05-01
As presently defined, post-traumatic stress disorder (PTSD) is an amalgam of symptoms falling into: re-experiencing of the trauma, avoidance of reminders of it, emotional numbing and hyperarousal. PTSD has a well-known proximate cause, commonly occurring after a life-threatening event that induces a response of intense fear, horror, and helplessness. Much of the advancement in understanding of the neurobiology of PTSD has emerged from conceptualizing the disorder as one that involves substantial dysfunction in fear processing. This article reviews recent knowledge of fear processing markers in PTSD. A systematic search was performed of reports within the specific three-year publication time period of January 2010 to December 2012. We identified a total of 31 studies reporting fear processing markers in PTSD. We further categorized them according to the following classification: (1) neural-activation markers (n=10), (2) psychophysiological markers (n=14), and (3) behavioral markers (n=7). Across most studies reviewed here, significant differences between individuals with PTSD and healthy controls were shown. Methodological, theoretical and clinical implications were discussed.
Combining markers with and without the limit of detection
Dong, Ting; Liu, Catherine Chunling; Petricoin, Emanuel F.; Tang, Liansheng Larry
2014-01-01
In this paper, we consider the combination of markers with and without the limit of detection (LOD). LOD is often encountered when measuring proteomic markers. Because of the limited detecting ability of an equipment or instrument, it is difficult to measure markers at a relatively low level. Suppose that after some monotonic transformation, the marker values approximately follow multivariate normal distributions. We propose to estimate distribution parameters while taking the LOD into account, and then combine markers using the results from the linear discriminant analysis. Our simulation results show that the ROC curve parameter estimates generated from the proposed method are much closer to the truth than simply using the linear discriminant analysis to combine markers without considering the LOD. In addition, we propose a procedure to select and combine a subset of markers when many candidate markers are available. The procedure based on the correlation among markers is different from a common understanding that a subset of the most accurate markers should be selected for the combination. The simulation studies show that the accuracy of a combined marker can be largely impacted by the correlation of marker measurements. Our methods are applied to a protein pathway dataset to combine proteomic biomarkers to distinguish cancer patients from non-cancer patients. PMID:24132938
[Biological markers of alcoholism].
Marcos Martín, M; Pastor Encinas, I; Laso Guzmán, F J
2005-09-01
Diagnosis of alcoholism is very important, given its high prevalence and possibility of influencing the disease course. For this reason, the so-called biological markers of alcoholism are useful. These are analytic parameters that alter in the presence of excessive alcohol consumption. The two most relevant markers are the gamma-glutamyltranspeptidase and carbohydrate deficient transferrin. With this clinical comment, we aim to contribute to the knowledge of these tests and promote its use in the clinical practice.
Garnero, P; Bianchi, F; Carlier, M C; Genty, V; Jacob, N; Kamel, S; Kindermans, C; Plouvier, E; Pressac, M; Souberbielle, J C
2000-01-01
Biochemical markers of bone turnover have been developed over the past 20 years that are more specific for bone tissue than conventional ones such as total alkaline phosphatase and urinary hydroxyproline. They have been widely used in clinical research and in clinical trials of new therapies as secondary end points of treatment efficacy. Most of the interest has been devoted to their use in postmenopausal osteoporosis, a condition characterized by subtle modifications of bone metabolism that cannot be detected readily by conventional markers of bone turnover. Although several recent studies have suggested that biochemical markers may be used for the management of the individual patient in routine clinical practice, this has not been clearly defined and is a matter of debate. Because of the crucial importance to clarify this issue, the Société Francaise de Biologie Clinique prompted an expert committee to summarize the available data and to make recommendations. The following paper includes a review on the biochemical and analytical aspects of the markers of bone formation and resorption and on the sources of variability such as sex, age, menstrual cycle, pregnancy and lactation, physical activity, seasonal variation and effects of diseases and treatments. We will also describe the effects of pre-analytical factors on the measurements of the different markers. Finally based on that review, we will make practical recommendations for the use of these markers in order to minimize the variability of the measurements and improve the clinical interpretation of the data.
The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV infection
Mehraj, Vikram; Jenabian, Mohammad-Ali; Ponte, Rosalie; Lebouché, Bertrand; Costiniuk, Cecilia; Thomas, Réjean; Baril, Jean-Guy; LeBlanc, Roger; Cox, Joseph; Tremblay, Cécile; Routy, Jean-Pierre
2016-01-01
Objective: Following tissue barrier breaches, interleukin-33 (IL-33) is released as an ‘alarmin’ to induce inflammation. Soluble suppression of tumorigenicity 2 (sST2), as an IL-33 decoy receptor, contributes to limit inflammation. We assessed the relationship between the IL-33/ST2 axis and markers of gut mucosal damage in patients with early (EHI) and chronic HIV infection (CHI) and elite controllers. Design: Analyses on patients with EHI and CHI were conducted to determine IL-33/sST2 changes over time. Methods: IL-33 and sST2 levels were measured in plasma. Correlations between sST2 levels and plasma viral load, CD4+ and CD8+ T-cell counts, expression of T-cell activation/exhaustion markers, gut mucosal damage, microbial translocation and inflammation markers, as well as kynurenine/tryptophan ratio were assessed. Results: Plasma sST2 levels were elevated in EHI compared with untreated CHI and uninfected controls, whereas IL-33 levels were comparable in all groups. In EHI, sST2 levels were positively correlated with the CD8+ T-cell count and the percentage of T cells expressing activation and exhaustion markers, but not with viral load or CD4+ T-cell count. Plasma sST2 levels also correlated with plasma levels of gut mucosal damage, microbial translocation and kynurenine/tryptophan ratio and for some markers of inflammation. Prospective analyses showed that early antiretroviral therapy had no impact on sST2 levels, whereas longer treatment duration initiated during CHI normalized sST2. Conclusion: As sST2 levels were elevated in EHI and were correlated with CD8+ T-cell count, immune activation, and microbial translocation, sST2 may serve as a marker of disease progression, gut damage and may directly contribute to HIV pathogenesis. PMID:27045377
Di Gaspero, G; Cipriani, G; Adam-Blondon, A-F; Testolin, R
2007-05-01
Genetic maps functionally oriented towards disease resistance have been constructed in grapevine by analysing with a simultaneous maximum-likelihood estimation of linkage 502 markers including microsatellites and resistance gene analogs (RGAs). Mapping material consisted of two pseudo-testcrosses, 'Chardonnay' x 'Bianca' and 'Cabernet Sauvignon' x '20/3' where the seed parents were Vitis vinifera genotypes and the male parents were Vitis hybrids carrying resistance to mildew diseases. Individual maps included 320-364 markers each. The simultaneous use of two mapping crosses made with two pairs of distantly related parents allowed mapping as much as 91% of the markers tested. The integrated map included 420 Simple Sequence Repeat (SSR) markers that identified 536 SSR loci and 82 RGA markers that identified 173 RGA loci. This map consisted of 19 linkage groups (LGs) corresponding to the grape haploid chromosome number, had a total length of 1,676 cM and a mean distance between adjacent loci of 3.6 cM. Single-locus SSR markers were randomly distributed over the map (CD = 1.12). RGA markers were found in 18 of the 19 LGs but most of them (83%) were clustered on seven LGs, namely groups 3, 7, 9, 12, 13, 18 and 19. Several RGA clusters mapped to chromosomal regions where phenotypic traits of resistance to fungal diseases such as downy mildew and powdery mildew, bacterial diseases such as Pierce's disease, and pests such as dagger and root-knot nematode, were previously mapped in different segregating populations. The high number of RGA markers integrated into this new map will help find markers linked to genetic determinants of different pest and disease resistances in grape.
Smart markers for watershed-based cell segmentation.
Koyuncu, Can Fahrettin; Arslan, Salim; Durmaz, Irem; Cetin-Atalay, Rengul; Gunduz-Demir, Cigdem
2012-01-01
Automated cell imaging systems facilitate fast and reliable analysis of biological events at the cellular level. In these systems, the first step is usually cell segmentation that greatly affects the success of the subsequent system steps. On the other hand, similar to other image segmentation problems, cell segmentation is an ill-posed problem that typically necessitates the use of domain-specific knowledge to obtain successful segmentations even by human subjects. The approaches that can incorporate this knowledge into their segmentation algorithms have potential to greatly improve segmentation results. In this work, we propose a new approach for the effective segmentation of live cells from phase contrast microscopy. This approach introduces a new set of "smart markers" for a marker-controlled watershed algorithm, for which the identification of its markers is critical. The proposed approach relies on using domain-specific knowledge, in the form of visual characteristics of the cells, to define the markers. We evaluate our approach on a total of 1,954 cells. The experimental results demonstrate that this approach, which uses the proposed definition of smart markers, is quite effective in identifying better markers compared to its counterparts. This will, in turn, be effective in improving the segmentation performance of a marker-controlled watershed algorithm.
Inflammation associated anemia and ferritin as disease markers in SLE
2012-01-01
Introduction In a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia. Methods A protein array was utilized to measure ferritin expression in the urine and serum of SLE patients and healthy controls. To confirm these results as well as the role of the iron transfer pathway in SLE, ELISAs were performed to measure ferritin and transferrin levels in inactive or active SLE patients and healthy controls. The relationship between ferritin/transferrin levels and inflammatory markers and anemia was next analyzed. Results Protein array results showed elevated ferritin levels in the serum and urine of lupus patients as compared to controls, which were further validated by ELISA. Increased ferritin levels correlated with measures of disease activity and anemia as well as inflammatory cytokine titers. Though active SLE patients had elevated urine transferrin, serum transferrin was reduced. Conclusion Urine ferritin and transferrin levels are elevated significantly in SLE patients and correlate with disease activity, bolstering previous reports. Most importantly, these changes correlated with the inflammatory state of the patients and anemia of chronic disease. Taken together, altered iron handling, inflammation and anemia of chronic disease constitute an ominous triad in SLE. PMID:22871034
Development and use of biochemical markers in osteoarthritis: current update.
Bay-Jensen, Anne C; Thudium, Christian S; Mobasheri, Ali
2018-01-01
There is an increasing demand for noninvasive and descriptive biochemical markers (biomarkers) in osteoarthritis; for enabling early drug development (including translational research), evaluating clinical trial at an early stage and for subtyping. Purpose of the review is to review and comment on current availability of such biomarkers. Many different biomarkers have been tested in the last 18 months. The main focus has been on testing whether the biomarkers, whether is reflect joint tissue turnover or inflammatory status, can differentiate osteoarthritis patients from healthy controls or whether the biomarkers are associated with progression. Less than a handful of studies, investigate the role of the biomarkers as response markers. Thus, there is still a great need for developing biomarkers that reflect disease activity and thereby can be used for treatment response or patient phenotyping. Osteoarthritis is the most common form of joint disease. This presents the osteoarthritis research community and pharmaceutical companies developing disease-modifying osteoarthritis drugs (DMOADs) with great opportunities. There are different osteoarthritis subtypes, which complicates the traditional approaches for developing new treatments. If we can identify new markers that can distinguish different subtypes, this can greatly facilitate drug development from early discovery to late clinical development.
Cell-surface marker discovery for lung cancer
Cohen, Allison S.; Khalil, Farah K.; Welsh, Eric A.; Schabath, Matthew B.; Enkemann, Steven A.; Davis, Andrea; Zhou, Jun-Min; Boulware, David C.; Kim, Jongphil; Haura, Eric B.; Morse, David L.
2017-01-01
Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients. PMID:29371917
Metabolic markers in sports medicine.
Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna
2012-01-01
be interpreted considering the athlete's body-mass index (BMI) and phase of the competitive season; use of cystatin C could be a reliable alternative to creatinine. Exercise and training induce adaptations in glucose metabolism which improve glucose utilization in athletes and are beneficial for reducing insulin insensitivity in nonathletes. Glucose metabolism differs slightly for different sports disciplines, as revealed in laboratory levels. Sport activities induce a blood lipid profile superior to that of sedentary subjects. There are few reports for a definitive conclusion, however. The differences between athletes and sedentary subjects are mainly due to high-density lipoprotein cholesterol (HDLC) concentrations in physically active individuals, although some differences among sport disciplines exist. The effect of sports on serum and urinary markers for bone metabolism is not univocal; further studies are needed to establish the real and effective influence of sport on bone turnover and especially to establish its beneficial effect.
Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.
López-Rodríguez, Rosario; Hernández-Bartolomé, Ángel; Borque, María Jesús; Rodríguez-Muñoz, Yolanda; Martín-Vílchez, Samuel; García-Buey, Luisa; González-Moreno, Leticia; Real-Martínez, Yolanda; Muñoz de Rueda, Paloma; Salmerón, Javier; Vidal-Castiñeira, José Ramón; López-Larrea, Carlos; Rodrigo, Luis; Moreno-Otero, Ricardo; Sanz-Cameno, Paloma
2017-01-01
Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients. NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates. Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74). The identified genetic variants in interferon signaling
Dehne, T.; Lindahl, A.; Brittberg, M.; Pruss, A.; Ringe, J.; Sittinger, M.; Karlsson, C.
2012-01-01
Objective: It is well known that expression of markers for WNT signaling is dysregulated in osteoarthritic (OA) bone. However, it is still not fully known if the expression of these markers also is affected in OA cartilage. The aim of this study was therefore to examine this issue. Methods: Human cartilage biopsies from OA and control donors were subjected to genome-wide oligonucleotide microarrays. Genes involved in WNT signaling were selected using the BioRetis database, KEGG pathway analysis was searched using DAVID software tools, and cluster analysis was performed using Genesis software. Results from the microarray analysis were verified using quantitative real-time PCR and immunohistochemistry. In order to study the impact of cytokines for the dysregulated WNT signaling, OA and control chondrocytes were stimulated with interleukin-1 and analyzed with real-time PCR for their expression of WNT-related genes. Results: Several WNT markers displayed a significantly altered expression in OA compared to normal cartilage. Interestingly, inhibitors of the canonical and planar cell polarity WNT signaling pathways displayed significantly increased expression in OA cartilage, while the Ca2+/WNT signaling pathway was activated. Both real-time PCR and immunohistochemistry verified the microarray results. Real-time PCR analysis demonstrated that interleukin-1 upregulated expression of important WNT markers. Conclusions: WNT signaling is significantly affected in OA cartilage. The result suggests that both the canonical and planar cell polarity WNT signaling pathways were partly inhibited while the Ca2+/WNT pathway was activated in OA cartilage. PMID:26069618
Couto, Claudia A; Bittencourt, Paulo L; Porta, Gilda; Abrantes-Lemos, Clarice P; Carrilho, Flair J; Guardia, Bianca D; Cançado, Eduardo L R
2014-02-01
Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity. © 2013 by the American Association for the Study of Liver Diseases.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...
Code of Federal Regulations, 2013 CFR
2013-10-01
... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...
Code of Federal Regulations, 2014 CFR
2014-10-01
... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...
Code of Federal Regulations, 2011 CFR
2011-10-01
... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...
Code of Federal Regulations, 2010 CFR
2010-10-01
... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Markers. 15.6 Section 15.6 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.6 Markers. No person shall willfully mark, deface or injure in any way, or displace, remove or tamper with any Preserve signs...
Haffajee, Zenobia Ayesha Mohamed; Kumar, Beena; Francis, Glenn; Peck, Martyn; Badrick, Tony
2017-11-20
The Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) Anatomical Pathology provides a comprehensive External Quality Assurance (EQA) exercise to review the reporting of immunohistochemistry (IHC) and in-situ hybridization (ISH) breast markers through an audit of clinical results. The aim of this exercise was to provide information regarding the quality of breast marker testing within clinical laboratories from 2005 to 2015. This comprehensive audit included estrogen, progesterone, and HER2 marker reporting. This was an important quality assurance activity established in response to ongoing difficulties experienced in laboratories in this area of testing.
Sudheer Pamidimarri, D V N; Singh, Sweta; Mastan, Shaik G; Patel, Jalpa; Reddy, Muppala P
2009-07-01
Jatropha curcas L., a multipurpose shrub has acquired significant economic importance for its seed oil which can be converted to biodiesel, is emerging as an alternative to petro-diesel. The deoiled seed cake remains after oil extraction is toxic and cannot be used as a feed despite having best nutritional contents. No quantitative and qualitative differences were observed between toxic and non-toxic varieties of J. curcas except for phorbol esters content. Development of molecular marker will enable to differentiate non-toxic from toxic variety in a mixed population and also help in improvement of the species through marker assisted breeding programs. The present investigation was undertaken to characterize the toxic and non-toxic varieties at molecular level and to develop PCR based molecular markers for distinguishing non-toxic from toxic or vice versa. The polymorphic markers were successfully identified specific to non-toxic and toxic variety using RAPD and AFLP techniques. Totally 371 RAPD, 1,442 AFLP markers were analyzed and 56 (15.09%) RAPD, 238 (16.49%) AFLP markers were found specific to either of the varieties. Genetic similarity between non-toxic and toxic verity was found to be 0.92 by RAPD and 0.90 by AFLP fingerprinting. In the present study out of 12 microsatellite markers analyzed, seven markers were found polymorphic. Among these seven, jcms21 showed homozygous allele in the toxic variety. The study demonstrated that both RAPD and AFLP techniques were equally competitive in identifying polymorphic markers and differentiating both the varieties of J. curcas. Polymorphism of SSR markers prevailed between the varieties of J. curcas. These RAPD and AFLP identified markers will help in selective cultivation of specific variety and along with SSRs these markers can be exploited for further improvement of the species through breeding and Marker Assisted Selection (MAS).
Ali, Marwan; Shah, Dhara; Pasha, Zeeshan; Jassim, Sarmad H; Jassim Jaboori, Assraa; Setabutr, Pete; Aakalu, Vinay K
2017-04-01
The accessory lacrimal glands (ALGs) are an understudied component of the tear functional unit, even though they are important in the development of dry eye syndrome (DES). To advance our understanding of aging changes, regenerative potential, and histologic correlates to human characteristics, we investigated human ALG tissue from surgical samples to determine the presence or absence of progenitor cell markers and lacrimal epithelial markers and to correlate marker expression to relevant patient characteristics. ALG tissues obtained from Muller's muscle conjunctival resection (MMCR) specimens were created using tissue microarrays (TMAs). Immunofluorescence staining of MMCR sections was performed using primary antibodies specific to cell protein markers. Cell marker localization in TMAs was then assessed by two blinded observers using a standardized scoring system. Patient characteristics including age, race, and status of ocular surface health were then compared against expression of stem cell markers. Human ALG expressed a number of epithelial markers, and in particular, histatin-1 was well correlated with the expression of epithelial markers and was present in most acini. In addition, we noted the presence of precursor cell markers nestin, ABCG2, and CD90 in ALG tissue. There was a decrease in precursor cell marker expression with increasing age. Finally, we noted that a negative association was present between histatin-1 expression and DES. Thus, we report for the first time that human ALG tissues contain precursor marker-positive cells and that this marker expression may decrease with increasing age. Moreover, histatin-1 expression may be decreased in DES. Future studies will be performed to use these cell markers to isolate and culture lacrimal epithelial cells from heterogeneous tissues, determine the relevance of histatin-1 expression to DES, and isolate candidate precursor cells from ALG tissue.
30 CFR 816.11 - Signs and markers.
Code of Federal Regulations, 2013 CFR
2013-07-01
...) Identification signs shall be displayed at each point of access to the permit area from public roads. (2) Signs... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Signs and markers. 816.11 Section 816.11... § 816.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall— (1) Be...
30 CFR 816.11 - Signs and markers.
Code of Federal Regulations, 2012 CFR
2012-07-01
...) Identification signs shall be displayed at each point of access to the permit area from public roads. (2) Signs... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Signs and markers. 816.11 Section 816.11... § 816.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall— (1) Be...
30 CFR 816.11 - Signs and markers.
Code of Federal Regulations, 2014 CFR
2014-07-01
...) Identification signs shall be displayed at each point of access to the permit area from public roads. (2) Signs... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Signs and markers. 816.11 Section 816.11... § 816.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall— (1) Be...
30 CFR 816.11 - Signs and markers.
Code of Federal Regulations, 2010 CFR
2010-07-01
...) Identification signs shall be displayed at each point of access to the permit area from public roads. (2) Signs... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Signs and markers. 816.11 Section 816.11... § 816.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall— (1) Be...
30 CFR 816.11 - Signs and markers.
Code of Federal Regulations, 2011 CFR
2011-07-01
...) Identification signs shall be displayed at each point of access to the permit area from public roads. (2) Signs... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Signs and markers. 816.11 Section 816.11... § 816.11 Signs and markers. (a) Specifications. Signs and markers required under this part shall— (1) Be...
[Immunological Markers in Organ Transplantation].
Beckmann, J H; Heits, N; Braun, F; Becker, T
2017-04-01
The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation. Georg Thieme Verlag KG Stuttgart · New York.
IL-32 is a molecular marker of a host defense network in human tuberculosis
Montoya, Dennis; Inkeles, Megan S.; Liu, Phillip T.; Realegeno, Susan; Teles, Rosane M. B.; Vaidya, Poorva; Munoz, Marcos A.; Schenk, Mirjam; Swindell, William R.; Chun, Rene; Zavala, Kathryn; Hewison, Martin; Adams, John S.; Horvath, Steve; Pellegrini, Matteo; Bloom, Barry R.; Modlin, Robert L.
2014-01-01
Tuberculosis is a leading cause of infectious disease–related death worldwide; however, only 10% of people infected with Mycobacterium tuberculosis develop disease. Factors that contribute to protection could prove to be promising targets for M. tuberculosis therapies. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify potential human candidate markers of host defense by studying gene expression profiles of macrophages, cells that, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene coexpression network analysis revealed an association between the cytokine interleukin-32 (IL-32) and the vitamin D antimicrobial pathway in a network of interferon-γ– and IL-15–induced “defense response” genes. IL-32 induced the vitamin D–dependent antimicrobial peptides cathelicidin and DEFB4 and to generate antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. In addition, the IL-15–induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent compared with active tuberculosis or healthy controls and a coexpression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15–induced gene network. As maintaining M. tuberculosis in a latent state and preventing transition to active disease may represent a form of host resistance, these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis. PMID:25143364
IL-32 is a molecular marker of a host defense network in human tuberculosis.
Montoya, Dennis; Inkeles, Megan S; Liu, Phillip T; Realegeno, Susan; Teles, Rosane M B; Vaidya, Poorva; Munoz, Marcos A; Schenk, Mirjam; Swindell, William R; Chun, Rene; Zavala, Kathryn; Hewison, Martin; Adams, John S; Horvath, Steve; Pellegrini, Matteo; Bloom, Barry R; Modlin, Robert L
2014-08-20
Tuberculosis is a leading cause of infectious disease-related death worldwide; however, only 10% of people infected with Mycobacterium tuberculosis develop disease. Factors that contribute to protection could prove to be promising targets for M. tuberculosis therapies. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify potential human candidate markers of host defense by studying gene expression profiles of macrophages, cells that, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene coexpression network analysis revealed an association between the cytokine interleukin-32 (IL-32) and the vitamin D antimicrobial pathway in a network of interferon-γ- and IL-15-induced "defense response" genes. IL-32 induced the vitamin D-dependent antimicrobial peptides cathelicidin and DEFB4 and to generate antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. In addition, the IL-15-induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent compared with active tuberculosis or healthy controls and a coexpression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15-induced gene network. As maintaining M. tuberculosis in a latent state and preventing transition to active disease may represent a form of host resistance, these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis. Copyright © 2014, American Association for the Advancement of Science.
Immunocytochemistry of the olfactory marker protein.
Monti-Graziadei, G A; Margolis, F L; Harding, J W; Graziadei, P P
1977-12-01
The olfactory marker protein has been localized, by means of immunohistochemical techniques in the primary olfactory neurons of mice. The olfactory marker protein is not present in the staminal cells of the olfactory neuroepithelium, and the protein may be regarded as indicative of the functional stage of the neurons. Our data indicate that the olfactory marker protein is present in the synaptic terminals of the olfactory neurons at the level of the olfactory bulb glomeruli. The postsynaptic profiles of both mitral and periglomerular cells are negative.
Converging Intracranial Markers of Conscious Access
Gaillard, Raphaël; Dehaene, Stanislas; Adam, Claude; Clémenceau, Stéphane; Hasboun, Dominique; Baulac, Michel; Cohen, Laurent; Naccache, Lionel
2009-01-01
We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG) in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (<300 ms), accompanied by induced gamma-band activity, but without coherent long-distance neural activity, suggesting a quickly dissipating feedforward wave. In contrast, conscious processing of unmasked words was characterized by the convergence of four distinct neurophysiological markers: sustained voltage changes, particularly in prefrontal cortex, large increases in spectral power in the gamma band, increases in long-distance phase synchrony in the beta range, and increases in long-range Granger causality. We argue that all of those measures provide distinct windows into the same distributed state of conscious processing. These results have a direct impact on current theoretical discussions concerning the neural correlates of conscious access. PMID:19296722
Bone metabolism markers and vitamin D in adolescent cyclists.
Olmedillas, Hugo; Gonzalez-Agüero, Alejandro; Rapún-López, Marta; Gracia-Marco, Luis; Gomez-Cabello, Alba; Pradas de la Fuente, Francisco; Moreno, Luís A; Casajús, José A; Vicente-Rodríguez, Germán
2018-02-03
This study aimed to describe bone metabolic activity in adolescent competitive cyclists compared to age-matched controls. The main result is that younger subjects present a higher bone turnover than the older ones. Moreover, cyclists under the age of 17 have higher scores on all markers than age-matched controls. The purpose of this study was to describe bone metabolic activity in adolescent competitive cyclists compared to age-matched controls. Twenty-two male adolescent cyclists between 14 and 20 years (y) and 20 age-matched controls participated in this study. Serum osteocalcin (OC), aminoterminal propeptide of type I procollagen (PINP), and β-isomerized C-telopeptides (β-CTX) were analyzed by electrochemiluminescence immunoassay (ECLIA); plasma 25 hydroxyvitamin D [25(OH)D] was analyzed by enzyme-linked immunosorbent assay (ELISA). Analysis of variance revealed no significant differences in bone metabolism markers and vitamin D between cyclists and controls. Cyclists over 17 y had a significantly lower concentration in bone formation and resorption biochemical markers compared to cyclists under 17 y (all P < 0.05). Moreover, controls over 17 y presented lower concentration for PINP (P < 0.05) compared to their peers under 17 y. Comparisons between cyclists and controls under 17 y revealed higher concentrations of OC and PINP (P < 0.05) in cyclists. Group interaction by age was found for OC, PINP, and β-CTX (P < 0.01). Cyclists over 17 y had higher concentrations of [25(OH)D] (P < 0.05) than age-matched controls. The present results support the idea that cycling during adolescence may be associated to a decrease in bone turnover that may affect bone health later in life.
Kent, Molly; Bardi, Massimo; Hazelgrove, Ashley; Sewell, Kaitlyn; Kirk, Emily; Thompson, Brooke; Trexler, Kristen; Terhune-Cotter, Brennan; Lambert, Kelly
2018-01-01
Coping strategies have been associated with differential stress responsivity, perhaps providing a valuable neurobiological marker for susceptibility to the emergence of depressogenic symptoms or vulnerability to other anxiety-related disorders. Rats profiled with a flexible coping phenotype, for example, exhibit increased neurobiological markers of emotional regulation compared to active and passive copers (Bardi et al., 2012; Lambert et al., 2014). In the current study, responses of male and female rats to prediction errors in a spatial foraging task (dry land maze; DLM) were examined after animals were exposed to chronic unpredictable stress (CUS). Brains were processed following the DLM training/assessment for fos-activation patterns and several measures of neuroplasticity in relevant areas. Behavioral responses observed during both the CUS and DLM phases of testing suggested that males and females employ different means of gathering information such as increased ambulatory exploration in males and rear responses in females. Fecal samples collected during baseline and following CUS swim exposure revealed higher corticosterone (CORT) in active copers, whereas flexible copers had higher dehydroepiandrosterone (DHEA) and DHEA/CORT ratios, both indications of enhanced emotional regulation. Focusing on the neural analysis, flexible copers exhibited fewer fos-immunoreactive cells in the basolateral amygdala and a trend toward lower activation in the insula while encountering the prediction error associated with the DLM probe trial. Coping profiles also differentially influenced markers of neuroplasticity; specifically, flexible copers exhibited higher levels nestin-immunoreactivity (ir). Further, less hippocampal glucocorticoid receptor-ir was observed in the flexible copers than the active and passive copers. In sum, flexible coping rats exhibited evidence of emotional resilience as indicated by several neurobiological measures; however, despite increased rates of
Soshi, Takahiro; Nakajima, Heizo; Hagiwara, Hiroko
2016-10-01
Static knowledge about the grammar of a natural language is represented in the cortico-subcortical system. However, the differences in dynamic verbal processing under different cognitive conditions are unclear. To clarify this, we conducted an electrophysiological experiment involving a semantic priming paradigm in which semantically congruent or incongruent word sequences (prime nouns-target verbs) were randomly presented. We examined the event-related brain potentials that occurred in response to congruent and incongruent target words that were preceded by primes with or without grammatical case markers. The two participant groups performed either the shallow (lexical judgment) or deep (direct semantic judgment) semantic tasks. We hypothesized that, irrespective of the case markers, the congruent targets would reduce centro-posterior N400 activities under the deep semantic condition, which induces selective attention to the semantic relatedness of content words. However, the same congruent targets with correct case markers would reduce lateralized negativity under the shallow semantic condition because grammatical case markers are related to automatic structural integration under semantically unattended conditions. We observed that congruent targets (e.g., 'open') that were preceded by primes with congruent case markers (e.g., 'shutter-object case') reduced lateralized negativity under the shallow semantic condition. In contrast, congruent targets, irrespective of case markers, consistently yielded N400 reductions under the deep semantic condition. To summarize, human neural verbal processing differed in response to the same grammatical markers in the same verbal expressions under semantically attended or unattended conditions.
Detection of occupational lead nephropathy using early renal markers.
Kumar, B D; Krishnaswamy, K
1995-01-01
Automotive use of leaded gasoline continues to be an important source of occupational exposure to lead in India and other countries. The present study assessed the renal function and markers of early renal damage of 22 mechanics at three automobile garages. Urinary N-acetyl-3-D-glucosaminidase activity and beta-2-microglobulin levels were significantly increased in auto garage mechanics with blood leads of 30-69 micrograms/dL. A significant correlation was observed between blood lead levels and urinary N-acetyl-3-D-glucosaminidase activity but not with urine beta-2-microglobulin levels. A marginal impairment in creatinine clearance was not statistically significant. Urinary N-acetyl-3-D-glucosaminidase activity offers a sensitive monitor of blood lead and renal tubular injury.
Pheochromocytoma diagnosed pathologically with previous negative serum markers.
Heavner, Matthew G; Krane, Louis S; Winters, Shira M; Mirzazadeh, Majid
2015-10-01
Patients presenting with adrenal masses require workup with catecholamine or metabolite measurements to rule out pheochromocytoma. There is a select portion of patients with marker negative pheochromocytoma. The aim of this study is to compare patient characteristics and presentations between marker positive and marker negative tumors. We performed an IRB-approved retrospective chart review of 88 cases of pheochromocytoma excised at our institution from 1995 to 2013. We considered any abnormal elevation in diagnostic test to be marker-positive. Seventy-eight cases had laboratory results available. Among these, seven had no elevations in laboratory testing. There was no difference in age or tumor size, but marker-negative patients had higher BMI than marker-positive patients. Marker negative patients were more likely to present with vertigo/dizziness (P = 0.003). Neither was more likely to have a genetic syndrome associated with risk of pheochromocytoma. Marker-negative pheochromocytoma is uncommon, representing 9% of cases in our series. Of patients with adrenal masses or presentation suggesting catecholamine excess with normal labs, those with vertigo/dizziness may warrant a metaiodobenzylguanidine scan or repeat testing to avoid missing pheochromocytoma. Clinicians may need a high degree of suspicion for pheochromocytoma in patients with negative testing and elevated BMI. © 2015 Wiley Periodicals, Inc.
Jin, Peng; van der Horst, Astrid; de Jong, Rianne; van Hooft, Jeanin E; Kamphuis, Martijn; van Wieringen, Niek; Machiels, Melanie; Bel, Arjan; Hulshof, Maarten C C M; Alderliesten, Tanja
2015-12-01
The aim of this study was to quantify interfractional esophageal tumor position variation using markers and investigate the use of markers for setup verification. Sixty-five markers placed in the tumor volumes of 24 esophageal cancer patients were identified in computed tomography (CT) and follow-up cone-beam CT. For each patient we calculated pairwise distances between markers over time to evaluate geometric tumor volume variation. We then quantified marker displacements relative to bony anatomy and estimated the variation of systematic (Σ) and random errors (σ). During bony anatomy-based setup verification, we visually inspected whether the markers were inside the planning target volume (PTV) and attempted marker-based registration. Minor time trends with substantial fluctuations in pairwise distances implied tissue deformation. Overall, Σ(σ) in the left-right/cranial-caudal/anterior-posterior direction was 2.9(2.4)/4.1(2.4)/2.2(1.8) mm; for the proximal stomach, it was 5.4(4.3)/4.9(3.2)/1.9(2.4) mm. After bony anatomy-based setup correction, all markers were inside the PTV. However, due to large tissue deformation, marker-based registration was not feasible. Generally, the interfractional position variation of esophageal tumors is more pronounced in the cranial-caudal direction and in the proximal stomach. Currently, marker-based setup verification is not feasible for clinical routine use, but markers can facilitate the setup verification by inspecting whether the PTV covers the tumor volume adequately. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
St. Louis inlaid pavement marker survey.
DOT National Transportation Integrated Search
2017-02-01
This report presents results from a survey of a diverse group of motorists perceptions and opinions of inlaid pavement markers. Respondents participated in one of three ways: They (a) experienced the markers first-hand by driving a designated route w...
Compact tracking of surgical instruments through structured markers.
Alberto Borghese, N; Frosio, I
2013-07-01
Virtual and augmented reality surgery calls for reliable and efficient tracking of the surgical instruments in the virtual or real operating theatre. The most diffused approach uses three or more not aligned markers, attached to each instrument and surveyed by a set of cameras. However, the structure required to carry the markers does modify the instrument's mass distribution and can interfere with surgeon movements. To overcome these problems, we propose here a new methodology, based on structured markers, to compute the six degrees of freedom of a surgical instrument. Two markers are attached on the instrument axis and one of them has a stripe painted over its surface. We also introduce a procedure to compute with high accuracy the markers center on the cameras image, even when partially occluded by the instrument's axis or by other structures. Experimental results demonstrate the reliability and accuracy of the proposed approach. The introduction of structured passive markers can open new possibilities to accurate tracking, combining markers detection with real-time image processing.
2015-01-01
Background microRNA (miRNA) expression plays an influential role in cancer classification and malignancy, and miRNAs are feasible as alternative diagnostic markers for pancreatic cancer, a highly aggressive neoplasm with silent early symptoms, high metastatic potential, and resistance to conventional therapies. Methods In this study, we evaluated the benefits of multi-omics data analysis by integrating miRNA and mRNA expression data in pancreatic cancer. Using support vector machine (SVM) modelling and leave-one-out cross validation (LOOCV), we evaluated the diagnostic performance of single- or multi-markers based on miRNA and mRNA expression profiles from 104 PDAC tissues and 17 benign pancreatic tissues. For selecting even more reliable and robust markers, we performed validation by independent datasets from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) data depositories. For validation, miRNA activity was estimated by miRNA-target gene interaction and mRNA expression datasets in pancreatic cancer. Results Using a comprehensive identification approach, we successfully identified 705 multi-markers having powerful diagnostic performance for PDAC. In addition, these marker candidates annotated with cancer pathways using gene ontology analysis. Conclusions Our prediction models have strong potential for the diagnosis of pancreatic cancer. PMID:26328610
Biomarkers and Surrogate Markers: An FDA Perspective
Katz, Russell
2004-01-01
Summary: Interest is increasing rapidly in the use of surrogate markers as primary measures of the effectiveness of investigational drugs in definitive drug trials. Many such surrogate markers have been proposed as potential candidates for use in definitive effectiveness trials of agents to treat neurologic or psychiatric disease, but as of this date, there are no such markers that have been adequately “validated,” that is, shown to predict the effect of the treatment on the clinical outcome of interest. While the current law and regulations permit the United States Food and Drug Administration to base the approval of a drug product on a determination the effect of the drug on an unvalidated surrogate marker (that is, one for which it is not known that an effect on the surrogate actually predicts the desired clinical benefit), there are a number of difficulties in interpreting trials that use surrogate markers as primary measures of drug effect. In this article, the relevant regulatory context will be discussed, as well as the epistemological problems related to the interpretation of clinical trials in which unvalidated surrogate markers are used as primary outcomes. PMID:15717019
Atli, Abdullah; Bulut, Mahmut; Bez, Yasin; Kaplan, İbrahim; Özdemir, Pınar Güzel; Uysal, Cem; Selçuk, Hilal; Sir, Aytekin
2016-06-01
The traumatic life events, including earthquakes, war, and interpersonal conflicts, cause a cascade of psychological and biological changes known as post-traumatic stress disorder (PTSD). Malondialdehyde (MDA) is a reliable marker of lipid peroxidation, and paraoxonase is a known antioxidant enzyme. The aims of this study were to investigate the relationship between earthquake trauma, PTSD effects on oxidative stress and the levels of serum paraoxonase 1 (PON1) enzyme activity, and levels of serum MDA. The study was carried out on three groups called: the PTSD group, the traumatized with earthquake exercise group, and healthy control group, which contained 32, 31, and 38 individuals, respectively. Serum MDA levels and PON1 enzyme activities from all participants were measured, and the results were compared across all groups. There were no significant differences between the PTSD patients and non-PTSD earthquake survivors in terms of the study variables. The mean PON1 enzyme activity from PTSD patients was significantly lower, while the mean MDA level was significantly higher than that of the healthy control group (p < 0.01 for both measurements). Similarly, earthquake survivors who did not develop PTSD showed higher MDA levels and lower PON1 activity when compared to healthy controls. However, the differences between these groups did not reach a statistically significant level. Increased MDA level and decreased PON1 activity measured in PTSD patients after earthquake and may suggest increased oxidative stress in these patients. The nonsignificant trends that are observed in lipid peroxidation markers of earthquake survivors may indicate higher impact of PTSD development on these markers than trauma itself. For example, PTSD diagnosis seems to add to the effect of trauma on serum MDA levels and PON1 enzyme activity. Thus, serum MDA levels and PON1 enzyme activity may serve as biochemical markers of PTSD diagnosis.
14 CFR 171.269 - Marker beacon performance requirements.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Marker beacon performance requirements. 171.269 Section 171.269 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... Landing System (ISMLS) § 171.269 Marker beacon performance requirements. ISMLS marker beacon equipment...
Greenwood, Edward J D; Schmidt, Fabian; Liégeois, Florian; Kondova, Ivanela; Herbert, Anaïs; Ngoubangoye, Barthelemy; Rouet, François; Heeney, Jonathan L
2014-01-01
Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4(+) T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.
[Expression of embryonic markers in pterygium derived mesenchymal cells].
Pascual, G; Montes, M A; Pérez-Rico, C; Pérez-Kohler, B; Bellón, J M; Buján, J
2010-12-01
Destruction of the limbal epithelium barrier is the most important mechanism of pterygium formation (conjunctiva proliferation, encroaching onto the cornea). It is thought to arise from activated and proliferating limbal epithelial stem cells. The objective of this study is to evaluate the presence of undifferentiated mesenchymal cells (stem cells) in cultured cells extracted from human pterygium. Cells from 6 human pterygium were isolated by explantation and placed in cultures with amniomax medium. Once the monolayer was reached the cells were seeded onto 24 well microplates. The cells were studied in the second sub-culture. The immunohistochemical expression of different embryonic stem cell markers, OCT3/4 and CD9, was analysed. The differentiated phenotypes were characterised with the monoclonal antibodies anti-CD31, α-actin and vimentin. All the cell populations obtained from pterygium showed vimentin expression. Less than 1% of the cells were positive for CD31 and α-actin markers. The majority of the cell population was positive for OCT3/4 and CD9. The cell population obtained from pterygium expressed mesenchymal cell phenotype and embryonic markers, such us OCT3/4 and CD9. This undifferentiated population could be involved in the large recurrence rate of this type of tissue after surgery. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.
Ali, Marwan; Shah, Dhara; Pasha, Zeeshan; Jassim, Sarmad H.; Jaboori, Assraa Jassim; Setabutr, Pete; Aakalu, Vinay K.
2017-01-01
Purpose The accessory lacrimal glands (ALG) are an understudied component of the tear functional unit, even though they are important in the development of dry eye syndrome (DES). To advance our understanding of aging changes, regenerative potential and histologic correlates to human characteristics, we investigated human ALG tissue from surgical samples to determine the presence or absence of progenitor cell markers and lacrimal epithelial markers and to correlate marker expression to relevant patient characteristics. Materials and Methods ALG tissues obtained from Muller’s Muscle Conjunctival Resection (MMCR) specimens were created using tissue microarrays (TMAs). Immunofluorescence staining of MMCR sections was performed using primary antibodies specific to cell protein markers. Cell marker localization in TMAs was then assessed by two blinded observers using a standardized scoring system. Patient characteristics including age, race, and status of ocular surface health were then compared against expression of stem cell markers. Results Human ALG expressed a number of epithelial markers, and in particular, histatin-1 was well correlated with the expression of epithelial markers and was present in most acini. In addition, we noted the presence of precursor cell markers nestin, ABCG2 and CD90 in ALG tissue. There was a decrease in precursor cell marker expression with increasing age. Finally, we noted that a negative association was present between histatin-1 expression and DES. Conclusions Thus, we report for the first time that human ALG tissues contain precursor marker positive cells and that this marker expression may decrease with increasing age. Moreover, histatin-1 expression may be decreased in DES. Future studies will be performed to use these cell markers to isolate and culture lacrimal epithelial cells from heterogeneous tissues, determine the relevance of histatin-1 expression to DES and isolate candidate precursor cells from ALG tissue. PMID:27612554
Choosing the correct forensic marker(s) in currency, document, and product protection
NASA Astrophysics Data System (ADS)
Plimmer, Jeremy J.
2006-02-01
The use of forensic markers (often known as 'tags' or taggants) as authenticity agents in currency, document and product provenance protection is gaining increased acceptance. There is now a wide choice to be made from a variety of technologies available from a number of suppliers. What criteria should be employed to aid the selection of the most appropriate technology? This paper will identify by type the range of technologies available. The use of tags and identification markers in all forms of authenticity test is highly dependent upon criteria such as the method used to deliver the marking component and the equipment needed to identify and extract the marking agent during the authorisation process. For instance, the type of marking system that can be effectively used in currency protection will require different attributes to that of a marker that identifies the authenticity of say a pharmaceutical product or the provenance of a precious stone. Such marking systems offer quality results to potential users, all of whom posses their own distinctive needs. However the correct choice will be driven by a decision making process that involves cost, speed of application, ease of recovery and low risk of compromise as well suitability for purpose. This paper will briefly identify the way forensic markers can be utilised in protecting users from various risks such as counterfeiting, dilution and refilling. This paper will also explore the technical aspects of each process with regard to characteristics and components involved in the system and then analyse the suitability of a range of available technologies to address risks on a sector by sector basis.
A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
NASA Astrophysics Data System (ADS)
Ariey, Frédéric; Witkowski, Benoit; Amaratunga, Chanaki; Beghain, Johann; Langlois, Anne-Claire; Khim, Nimol; Kim, Saorin; Duru, Valentine; Bouchier, Christiane; Ma, Laurence; Lim, Pharath; Leang, Rithea; Duong, Socheat; Sreng, Sokunthea; Suon, Seila; Chuor, Char Meng; Bout, Denis Mey; Ménard, Sandie; Rogers, William O.; Genton, Blaise; Fandeur, Thierry; Miotto, Olivo; Ringwald, Pascal; Le Bras, Jacques; Berry, Antoine; Barale, Jean-Christophe; Fairhurst, Rick M.; Benoit-Vical, Françoise; Mercereau-Puijalon, Odile; Ménard, Didier
2014-01-01
Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain (`K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.
Neural Markers of Responsiveness to the Environment in Human Sleep.
Andrillon, Thomas; Poulsen, Andreas Trier; Hansen, Lars Kai; Léger, Damien; Kouider, Sid
2016-06-15
Sleep is characterized by a loss of behavioral responsiveness. However, recent research has shown that the sleeping brain is not completely disconnected from its environment. How neural activity constrains the ability to process sensory information while asleep is yet unclear. Here, we instructed human volunteers to classify words with lateralized hand responses while falling asleep. Using an electroencephalographic (EEG) marker of motor preparation, we show how responsiveness is modulated across sleep. These modulations are tracked using classic event-related potential analyses complemented by Lempel-Ziv complexity (LZc), a measure shown to track arousal in sleep and anesthesia. Neural activity related to the semantic content of stimuli was conserved in light non-rapid eye movement (NREM) sleep. However, these processes were suppressed in deep NREM sleep and, importantly, also in REM sleep, despite the recovery of wake-like neural activity in the latter. In NREM sleep, sensory activations were counterbalanced by evoked down states, which, when present, blocked further processing of external information. In addition, responsiveness markers correlated positively with baseline complexity, which could be related to modulation in sleep depth. In REM sleep, however, this relationship was reversed. We therefore propose that, in REM sleep, endogenously generated processes compete with the processing of external input. Sleep can thus be seen as a self-regulated process in which external information can be processed in lighter stages but suppressed in deeper stages. Last, our results suggest drastically different gating mechanisms in NREM and REM sleep. Previous research has tempered the notion that sleepers are isolated from their environment. Here, we pushed this idea forward and examined, across all sleep stages, the brain's ability to flexibly process sensory information, up to the decision level. We extracted an EEG marker of motor preparation to determine the
Farooqui, Javed Hussain; Koul, Archana; Dutta, Ranjan; Shroff, Noshir Minoo
2016-01-01
To compare the accuracy of two different methods of preoperative marking for toric intraocular lens (IOL) implantation, bubble marker versus pendulum marker, as a means of establishing the reference point for the final alignment of the toric IOL to achieve an outcome as close as possible to emmetropia. Toric IOLs were implanted in 180 eyes of 110 patients. One group (55 patients) had preoperative marking of both eyes done with bubble marker (ASICO AE-2791TBL) and the other group (55 patients) with pendulum marker (Rumex(®)3-193). Reference marks were placed at 3-, 6-, and 9-o'clock positions on the limbus. Slit-lamp photographs were analyzed using Adobe Photoshop (version 7.0). Amount of alignment error (in degrees) induced in each group was measured. Mean absolute rotation error in the preoperative marking in the horizontal axis was 2.42±1.71 in the bubble marker group and 2.83±2.31in the pendulum marker group (P=0.501). Sixty percent of the pendulum group and 70% of the bubble group had rotation error ≤3 (P=0.589), and 90% eyes of the pendulum group and 96.7% of the bubble group had rotation error ≤5 (P=0.612). Both preoperative marking techniques result in approximately 3 of alignment error. Both marking techniques are simple, predictable, reproducible and easy to perform.
Selman, Colin; Blount, Jonathan D.; Pilkington, Jill G.; Watt, Kathryn A.; Pemberton, Josephine M.; Reid, Jane M.
2016-01-01
Oxidative stress (OS) is hypothesized to be a key physiological mechanism mediating life-history trade-offs, but evidence from wild populations experiencing natural environmental variation is limited. We tested the hypotheses that increased early life growth rate increases OS, and that increased OS reduces first-winter survival, in wild Soay sheep (Ovis aries) lambs. We measured growth rate and first-winter survival for four consecutive cohorts, and measured two markers of oxidative damage (malondialdehyde (MDA), protein carbonyls (PC)) and two markers of antioxidant (AOX) protection (total AOX capacity (TAC), superoxide dismutase (SOD)) from blood samples. Faster lamb growth was weakly associated with increased MDA, but not associated with variation in the other three markers. Lambs with higher SOD activity were more likely to survive their first winter, as were male but not female lambs with lower PC concentrations. Survival did not vary with MDA or total TAC. Key predictions relating OS to growth and survival were therefore supported in some OS markers, but not others. This suggests that different markers capture different aspects of the complex relationships between individual oxidative state, physiology and fitness, and that overarching hypotheses relating OS to life-history variation cannot be supported or refuted by studying individual markers. PMID:27733545
GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus.
Chung, C P; Ormseth, M J; Connelly, M A; Oeser, A; Solus, J F; Otvos, J D; Raggi, P; Stein, C M
2016-03-01
GlycA is a novel marker of systemic inflammation detected by nuclear magnetic resonance (NMR) spectroscopy. In the general population, GlycA is correlated with inflammatory markers such as C-reactive protein (CRP) and associated with coronary heart disease and diabetes. The utility of GlycA in patients with systemic lupus erythematosus (SLE) has not been defined. Therefore, we tested the hypothesis that GlycA concentrations are elevated in patients with SLE and associated with other markers of inflammation and coronary atherosclerosis. We compared concentrations of GlycA, detected by NMR, in 116 patients with SLE and 84 control subjects frequency-matched for age, sex, and race. SLE disease activity index (SLEDAI) and the SLE Collaborating Clinics damage index (SLICC) were calculated. Acute phase reactants, a panel of cytokines, and a lipid panel were measured. Electron beam computer tomography (EBCT) was used to quantify coronary artery calcification, a measure of coronary artery atherosclerosis. Patients with SLE had higher concentrations of GlycA (398 (350-445)) than control subjects (339 (299-391)) µmol/L, p < 0.001. In patients with SLE, concentrations of GlycA were significantly associated with sedimentation rate (rho = 0.43), C-reactive protein (rho = 0.59), e-selectin (rho = 0.28), intracellular adhesion molecule-1 (rho = 0.30), triglycerides (rho = 0.45), all p < 0.0023 to account for multiple comparisons, but not with creatinine, SLEDAI, SLICC, or coronary calcium scores. Concentrations of GlycA are higher in patients with SLE than control subjects and associated with markers of inflammation but not with SLE disease activity or chronicity scores or coronary artery calcification. © The Author(s) 2015.
Huerta, Mario; Munyi, Marc; Expósito, David; Querol, Enric; Cedano, Juan
2014-06-15
The microarrays performed by scientific teams grow exponentially. These microarray data could be useful for researchers around the world, but unfortunately they are underused. To fully exploit these data, it is necessary (i) to extract these data from a repository of the high-throughput gene expression data like Gene Expression Omnibus (GEO) and (ii) to make the data from different microarrays comparable with tools easy to use for scientists. We have developed these two solutions in our server, implementing a database of microarray marker genes (Marker Genes Data Base). This database contains the marker genes of all GEO microarray datasets and it is updated monthly with the new microarrays from GEO. Thus, researchers can see whether the marker genes of their microarray are marker genes in other microarrays in the database, expanding the analysis of their microarray to the rest of the public microarrays. This solution helps not only to corroborate the conclusions regarding a researcher's microarray but also to identify the phenotype of different subsets of individuals under investigation, to frame the results with microarray experiments from other species, pathologies or tissues, to search for drugs that promote the transition between the studied phenotypes, to detect undesirable side effects of the treatment applied, etc. Thus, the researcher can quickly add relevant information to his/her studies from all of the previous analyses performed in other studies as long as they have been deposited in public repositories. Marker-gene database tool: http://ibb.uab.es/mgdb © The Author 2014. Published by Oxford University Press.
Gericke, Sebastian; Lübken, Tilo; Wolf, Diana; Kaiser, Martin; Hannig, Christian; Speer, Karl
2018-02-28
Parts of Salvia species such as its flowers and leaves are currently used as a culinary herb and for some medicinal applications. To distinguish the different sage extracts it is necessary to analyze their individual chemical compositions. Their characteristic compounds might be established as markers to differentiate between sage flowers and leaf extracts or to determine the manufacturing technology and storage conditions. Tri-p-coumaroylspermidine can be detected only in flowers and has been described here for Salvia and Lavandula species for the first time. Markers for oxidation processes are the novel compounds salviquinone A and B, which were generated from carnosol by exposure to oxygen. Caffeic acid ethyl ester was established as an indirect marker for the usage of ethanol as extraction solvent. The compounds were identified by LC-QTOF-HRESIMS, LC-MS, NMR, IR, and single-crystal X-ray diffraction after isolation by semipreparative HPLC. Furthermore, sage flower resin showed interesting antibacterial in vitro activities against Gram-positive and Gram-negative bacteria.
Blood antioxidant enzymes as markers of exposure or effect in coal miners.
Perrin-Nadif, R; Auburtin, G; Dusch, M; Porcher, J M; Mur, J M
1996-01-01
OBJECTIVE--To investigate if blood Cu++/Zn++ superoxide dismutase, glutathione peroxidase, catalase, and total plasma antioxidant activities could be markers of biological activity resulting from exposure to respirable coal mine dust in active miners, and of pneumoconiosis in retired miners. METHODS--Blood samples were randomly obtained from active surface workers (n = 30) and underground miners (n = 34), and from retired miners without (n = 21), and with (n = 33) pneumoconiosis. Antioxidant enzyme activities and total plasma antioxidants were measured in erythrocytes and plasma. Non-parametric tests were completed by analyses of covariance to compare antioxidants between groups, taking into account potential confounding factors (age, smoking history (pack-years)). RESULTS--Erythrocyte Cu++/Zn++ superoxide dismutase activity was significantly higher in the group of underground miners than the group of surface workers. The differences in total plasma antioxidants and plasma glutathione peroxidase activity between both groups were related to age. Glutathione peroxidase activity increased in the plasma of retired miners with pneumoconiosis, compared with retired miners without pneumoconiosis. No differences were found either in erythrocyte antioxidant enzyme activities or in total plasma antioxidants between the groups of retired miners without and with pneumoconiosis. CONCLUSIONS--In this study, erythrocyte Cu++/Zn++ superoxide dismutase activity may be considered as a marker of effect of respirable coal mine dust in exposed workers. This result is in agreement with the hypothesis that reactive oxygen species are involved in cell injury induced by coal mine dust, and may be predictive of the degree of inflammation and pneumoconiosis induced by coal mine dust. The increase in glutathione peroxidase activity in the plasma of retired miners with pneumoconiosis may be the result of a response to the increasing hydrogen peroxide (H2O2) production due to the disease
DNA marker technology for wildlife conservation
Arif, Ibrahim A.; Khan, Haseeb A.; Bahkali, Ali H.; Al Homaidan, Ali A.; Al Farhan, Ahmad H.; Al Sadoon, Mohammad; Shobrak, Mohammad
2011-01-01
Use of molecular markers for identification of protected species offers a greater promise in the field of conservation biology. The information on genetic diversity of wildlife is necessary to ascertain the genetically deteriorated populations so that better management plans can be established for their conservation. Accurate classification of these threatened species allows understanding of the species biology and identification of distinct populations that should be managed with utmost care. Molecular markers are versatile tools for identification of populations with genetic crisis by comparing genetic diversities that in turn helps to resolve taxonomic uncertainties and to establish management units within species. The genetic marker analysis also provides sensitive and useful tools for prevention of illegal hunting and poaching and for more effective implementation of the laws for protection of the endangered species. This review summarizes various tools of DNA markers technology for application in molecular diversity analysis with special emphasis on wildlife conservation. PMID:23961128
Li, Ke; Li, Junfang; Su, Jin; Xiao, Xuefeng; Peng, Xiujuan; Liu, Feng; Li, Defeng; Zhang, Yi; Chong, Tao; Xu, Haiyu; Liu, Changxiao; Yang, Hongjun
2018-03-07
The quality evaluation of traditional Chinese medicine (TCM) formulations is needed to guarantee the safety and efficacy. In our laboratory, we established interaction rules between chemical quality control and biological activity evaluations to study Yuanhu Zhitong tablets (YZTs). Moreover, a quality marker (Q-marker) has recently been proposed as a new concept in the quality control of TCM. However, no appropriate methods are available for the identification of Q-markers from the complex TCM systems. We aimed to use an integrative pharmacological (IP) approach to further identify Q-markers from YZTs through the integration of multidisciplinary knowledge. In addition, data mining was used to determine the correlation between multiple constituents of this TCM and its bioactivity to improve quality control. The IP approach was used to identify the active constituents of YZTs and elucidate the molecular mechanisms by integrating chemical and biosynthetic analyses, drug metabolism, and network pharmacology. Data mining methods including grey relational analysis (GRA) and least squares support vector machine (LS-SVM) regression techniques, were used to establish the correlations among the constituents and efficacy, and dose efficacy in multiple dimensions. Seven constituents (tetrahydropalmatine, α-allocryptopine, protopine, corydaline, imperatorin, isoimperatorin, and byakangelicin) were identified as Q-markers of YZT using IP based on their high abundance, specific presence in the individual herbal constituents and the product, appropriate drug-like properties, and critical contribution to the bioactivity of the mixture of YZT constituents. Moreover, three Q-markers (protopine, α-allocryptopine, and corydaline) were highly correlated with the multiple bioactivities of the YZTs, as found using data mining. Finally, three constituents (tetrahydropalmatine, corydaline, and imperatorin) were chosen as minimum combinations that both distinguished the authentic
Liu, Hong; Shao-Gang, Ma; Liang, Cheng; Feng, Bai; Wei, Xu
2015-01-01
To investigate whether serum levels of butyrylcho-linesterase activity, cystatin C, and pre-albumin has the potential value as γ-glutamyl transferase in reflecting gestational diabetes mellitus and its fetal outcome. Seventy-six gestational diabetes mellitus women and 76 pregnancies with normal glucose tolerance in the second trimester were enrolled. Maternal serum parameters of butyrylcholinesterase activity, γ-glutamyl transferase, cystatin C, and pre-albumin were detected and evaluated. The pregnant complications and fetal outcome were also evaluated. Levels of butyrylcholinesterase activity, γ-glutamyl transferase, cystatin C, pre-albumin and glycemic variables were higher in the gestational diabetes mellitus patients than in the controls. Levels of butyrylcholinesterase activity were significantly correlated to the levels of fasting plasma glucose, cystatin C, and γ- glutamyl transferase (p < 0.05) in the gestational diabetes mellitus group. There were statistical differences in cases of preterm delivery, preeclampsia and postpartum hemorrhage. Higher levels of γ-glutamyl transferase and pre-albumin were risk markers for gestational diabetes mellitus (p < 0.05). The diagnosis curve demonstrated that γ-glutamyl transferase had a significant advantage over other markers (p < 0.001) but no significance compared with pre-albumin (p = 0.096). None of the detected markers showed predictive value for fetal outcome. Serum levels of butyrylcholinesterase activity, γ-glutamyl transferase, cystatin C and pre-albumin were correlated with gestational diabetes mellitus status but not with the fetal outcome. Pre-albumin can be equivalent as γ-glutamyl transferase in reflecting the presence of gestational diabetes mellitus.
Starup-Linde, J; Eriksen, S A; Lykkeboe, S; Handberg, A; Vestergaard, P
2014-06-01
This study examined whether markers of bone turnover differ between individuals with and without diabetes. Bone markers showed heterogeneity between studies and were discrepant for markers of bone creation and markers of bone degradation. Bone markers may be of lesser value in diabetes due to heterogeneity. The aim of this meta-analysis was to compare existing literature regarding changes in bone markers among diabetics compared to healthy controls. To exclude that blood glucose levels among diabetes patients could influence the assays used for determining bone turnover markers, a methodological study was performed. Medline at Pubmed Embase, Cinahl, Svemed+, Cochrane library, and Bibliotek.dk was searched in August 2012. The studies should examine biochemical bone turnover among diabetes patients in comparison to controls in an observational design. In the methodological study, fasting blood samples were drawn from two individuals. Glucose was added to the blood samples in different concentrations and OC, CTX, and procollagen type 1 amino terminal propeptide were measured after 0, 1, 2, and 3 h. Twenty-two papers fulfilled the criteria for the meta-analysis. From the pooled data in the meta-analysis, the bone markers osteocalcin (OC) (-1.15 ng/ml [-1.78,-0.52]) and C-terminal cross-linked telopeptide (CTX) (-0.14 ng/ml [-0.22, -0.05]) were significantly lower among diabetes patients than non-diabetes patients, however other markers did not differ. All markers displayed very high heterogeneity by I2 statistics. In the methodological study, the addition of glucose did not significantly change the bone markers neither by level of glucose nor with increasing incubation time. The dissociative pattern of biochemical bone markers of bone formation and bone resorption present in diabetes patients is thus not caused by glucose per se but may be modulated by unknown factors associated with diabetes mellitus.
Kulaeva, Olga A; Zhernakov, Aleksandr I; Afonin, Alexey M; Boikov, Sergei S; Sulima, Anton S; Tikhonovich, Igor A; Zhukov, Vladimir A
2017-01-01
Pea (Pisum sativum L.) is the oldest model object of plant genetics and one of the most agriculturally important legumes in the world. Since the pea genome has not been sequenced yet, identification of genes responsible for mutant phenotypes or desirable agricultural traits is usually performed via genetic mapping followed by candidate gene search. Such mapping is best carried out using gene-based molecular markers, as it opens the possibility for exploiting genome synteny between pea and its close relative Medicago truncatula Gaertn., possessing sequenced and annotated genome. In the last 5 years, a large number of pea gene-based molecular markers have been designed and mapped owing to the rapid evolution of "next-generation sequencing" technologies. However, the access to the complete set of markers designed worldwide is limited because the data are not uniformed and therefore hard to use. The Pea Marker Database was designed to combine the information about pea markers in a form of user-friendly and practical online tool. Version 1 (PMD1) comprises information about 2484 genic markers, including their locations in linkage groups, the sequences of corresponding pea transcripts and the names of related genes in M. truncatula. Version 2 (PMD2) is an updated version comprising 15944 pea markers in the same format with several advanced features. To test the performance of the PMD, fine mapping of pea symbiotic genes Sym13 and Sym27 in linkage groups VII and V, respectively, was carried out. The results of mapping allowed us to propose the Sen1 gene (a homologue of SEN1 gene of Lotus japonicus (Regel) K. Larsen) as the best candidate gene for Sym13, and to narrow the list of possible candidate genes for Sym27 to ten, thus proving PMD to be useful for pea gene mapping and cloning. All information contained in PMD1 and PMD2 is available at www.peamarker.arriam.ru.
Bassig, Bryan A.; Zhang, Luoping; Vermeulen, Roel; Tang, Xiaojiang; Li, Guilan; Hu, Wei; Guo, Weihong; Purdue, Mark P.; Yin, Songnian; Rappaport, Stephen M.; Shen, Min; Ji, Zhiying; Qiu, Chuangyi; Ge, Yichen; Hosgood, H.Dean; Reiss, Boris; Wu, Banghua; Xie, Yuxuan; Li, Laiyu; Yue, Fei; Freeman, Laura E.Beane; Blair, Aaron; Hayes, Richard B.; Huang, Hanlin; Smith, Martyn T.; Rothman, Nathaniel; Lan, Qing
2016-01-01
Benzene, formaldehyde (FA) and trichloroethylene (TCE) are ubiquitous chemicals in workplaces and the general environment. Benzene is an established myeloid leukemogen and probable lymphomagen. FA is classified as a myeloid leukemogen but has not been associated with non-Hodgkin lymphoma (NHL), whereas TCE has been associated with NHL but not myeloid leukemia. Epidemiologic associations between FA and myeloid leukemia, and between benzene, TCE and NHL are, however, still debated. Previously, we showed that these chemicals are associated with hematotoxicity in cross-sectional studies of factory workers in China, which included extensive personal monitoring and biological sample collection. Here, we compare and contrast patterns of hematotoxicity, monosomy 7 in myeloid progenitor cells (MPCs), and B-cell activation biomarkers across these studies to further evaluate possible mechanisms of action and consistency of effects with observed hematologic cancer risks. Workers exposed to benzene or FA, but not TCE, showed declines in cell types derived from MPCs, including granulocytes and platelets. Alterations in lymphoid cell types, including B cells and CD4+ T cells, and B-cell activation markers were apparent in workers exposed to benzene or TCE. Given that alterations in myeloid and lymphoid cell types are associated with hematological malignancies, our data provide biologic insight into the epidemiological evidence linking benzene and FA exposure with myeloid leukemia risk, and TCE and benzene exposure with NHL risk. PMID:27207665
Bassig, Bryan A; Zhang, Luoping; Vermeulen, Roel; Tang, Xiaojiang; Li, Guilan; Hu, Wei; Guo, Weihong; Purdue, Mark P; Yin, Songnian; Rappaport, Stephen M; Shen, Min; Ji, Zhiying; Qiu, Chuangyi; Ge, Yichen; Hosgood, H Dean; Reiss, Boris; Wu, Banghua; Xie, Yuxuan; Li, Laiyu; Yue, Fei; Freeman, Laura E Beane; Blair, Aaron; Hayes, Richard B; Huang, Hanlin; Smith, Martyn T; Rothman, Nathaniel; Lan, Qing
2016-07-01
Benzene, formaldehyde (FA) and trichloroethylene (TCE) are ubiquitous chemicals in workplaces and the general environment. Benzene is an established myeloid leukemogen and probable lymphomagen. FA is classified as a myeloid leukemogen but has not been associated with non-Hodgkin lymphoma (NHL), whereas TCE has been associated with NHL but not myeloid leukemia. Epidemiologic associations between FA and myeloid leukemia, and between benzene, TCE and NHL are, however, still debated. Previously, we showed that these chemicals are associated with hematotoxicity in cross-sectional studies of factory workers in China, which included extensive personal monitoring and biological sample collection. Here, we compare and contrast patterns of hematotoxicity, monosomy 7 in myeloid progenitor cells (MPCs), and B-cell activation biomarkers across these studies to further evaluate possible mechanisms of action and consistency of effects with observed hematologic cancer risks. Workers exposed to benzene or FA, but not TCE, showed declines in cell types derived from MPCs, including granulocytes and platelets. Alterations in lymphoid cell types, including B cells and CD4+ T cells, and B-cell activation markers were apparent in workers exposed to benzene or TCE. Given that alterations in myeloid and lymphoid cell types are associated with hematological malignancies, our data provide biologic insight into the epidemiological evidence linking benzene and FA exposure with myeloid leukemia risk, and TCE and benzene exposure with NHL risk. Published by Oxford University Press 2016.
Hu, Zhan; Ding, Xuezhi; Hu, Shengbiao; Sun, Yunjun; Xia, Liqiu
2013-12-01
Marker-free, genetically-modified rice was created by the tissue-specifically regulated Cre/loxP system, in which the Cre recombinase gene and hygromycin phosphotransferase gene (hpt) were flanked by two directly oriented loxP sites. Cre expression was activated by the tissue-specific promoter OsMADS45 in flower or napin in seed, resulting in simultaneous excision of the recombinase and marker genes. Segregation of T1 progeny was performed to select recombined plants. The excision was confirmed by PCR, Southern blot and sequence analyses indicating that efficiency varied from 10 to 53 % for OsMADS45 and from 12 to 36 % for napin. The expression of cry1Ac and vip3A was detected by RT-PCR analysis in marker-free transgenic rice. These results suggested that our tissue-specifically regulated Cre/loxP system could auto-excise marker genes from transgenic rice and alleviate public concerns about the security of GM crops.
Grønbaek, H; Sandahl, T D; Mortensen, C; Vilstrup, H; Møller, H J; Møller, S
2012-07-01
Activation of Kupffer cells may be involved in the pathogenesis of portal hypertension by release of vasoconstrictive substances and fibrosis due to co-activation of hepatic stellate cells. To study soluble plasma (s) CD163, a specific marker of activated macrophages, as a biomarker for portal hypertension in patients with liver cirrhosis. We measured sCD163 concentration and the hepatic venous pressure gradient (HVPG) by liver vein catheterisation in 81 cirrhosis patients (Child-Pugh CP-A: n = 26, CP-B: n = 29, CP-C: n = 26) and 22 healthy subjects. We also measured their cardiac output (CO), cardiac index and systemic vascular resistance (SVR). Liver status was examined by Child-Pugh and MELD-score. In cirrhosis, sCD163 concentration was nearly three times higher than in controls (4.7 ± 2.5 vs. 1.6 ± 0.5 mg/L, P < 0.001). sCD163 was also higher, as measured in steps by CP-score (P < 0.001). The HVPG rose steeply to an asymptote of 22 mmHg with sCD163 up to about 5 mg/L and not to higher values with higher sCD163. In a multivariate analysis, sCD163 was the only independent predictor of the HVPG but did not predict any of the systemic circulatory findings. sCD163 > 3.95 mg/L (upper normal limit) predicted HVPG ≥ 10 mmHg with a positive predictive value of 0.99. Circulating sCD163 originating from activated Kupffer cells is increased in cirrhosis with increasing Child-Pugh score and with increasing HVPG, and it is an independent predictor for HVPG. These findings support a primary role of macrophage activation in portal hypertension, and may indicate a target for biological intervention. © 2012 Blackwell Publishing Ltd.
Osteoporosis and Osteopathy Markers in Patients with Mastocytosis
Alpay Kanıtez, Nilüfer; Erer, Burak; Doğan, Öner; Büyükbabani, Nesimi; Baykal, Can; Sindel, Dilşad; Tanakol, Refik; Yavuz, Akif Selim
2015-01-01
Objective: Osteoporosis, osteosclerosis, and lytic bone lesions have been observed in patients with systemic mastocytosis (SM). We examined bone mineral density (BMD) biochemical turnover markers and serum tryptase levels in SM, which is considered a rare disease. Materials and Methods: Seventeen adult patients (5 females, 12 males; median age: 33 years, range: 20-64) with mastocytosis were included in this study. We investigated the value of quantitative ultrasound (QUS) of the calcaneus in the assessment of BMD in SM patients, as well as BMD of the lumbar spine (L1-L4), femoral neck, and distal radius using dual energy x-ray absorptiometry (DXA) and plasma tryptase levels, biochemical markers of bone turnover. Results: At lumbar spine L1-L4, the femoral neck, and the distal radius or as calcaneus stiffness, 12 of 17 patients had T-scores of less than -1 at least at 1 site, reflecting osteopenia. Three of 17 patients had T-scores showing osteoporosis (T-score <-2.5). There was no relationship between DXA and bone lesion severity. We also found a significant positive correlation between tryptase levels and disease severity, as well as between disease severity and pyridinoline (p<0.01 by Spearman’s test). Conclusion: DXA and calcaneal QUS may not be appropriate techniques to assess bone involvement in SM patients because of the effects of osteosclerosis. This study further shows that the osteoclastic marker pyridinoline is helpful in patients with severe disease activity and sclerotic bone lesions to show bone demineralization. PMID:25805674
21 CFR 878.4660 - Skin marker.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Skin marker. 878.4660 Section 878.4660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4660 Skin marker. (a) Identification. A skin...
21 CFR 878.4660 - Skin marker.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Skin marker. 878.4660 Section 878.4660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4660 Skin marker. (a) Identification. A skin...
21 CFR 878.4660 - Skin marker.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Skin marker. 878.4660 Section 878.4660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4660 Skin marker. (a) Identification. A skin...
21 CFR 878.4660 - Skin marker.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Skin marker. 878.4660 Section 878.4660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4660 Skin marker. (a) Identification. A skin...
Farooqui, Javed Hussain; Koul, Archana; Dutta, Ranjan; Shroff, Noshir Minoo
2016-01-01
AIM To compare the accuracy of two different methods of preoperative marking for toric intraocular lens (IOL) implantation, bubble marker versus pendulum marker, as a means of establishing the reference point for the final alignment of the toric IOL to achieve an outcome as close as possible to emmetropia. METHODS Toric IOLs were implanted in 180 eyes of 110 patients. One group (55 patients) had preoperative marking of both eyes done with bubble marker (ASICO AE-2791TBL) and the other group (55 patients) with pendulum marker (Rumex®3-193). Reference marks were placed at 3-, 6-, and 9-o'clock positions on the limbus. Slit-lamp photographs were analyzed using Adobe Photoshop (version 7.0). Amount of alignment error (in degrees) induced in each group was measured. RESULTS Mean absolute rotation error in the preoperative marking in the horizontal axis was 2.42±1.71 in the bubble marker group and 2.83±2.31in the pendulum marker group (P=0.501). Sixty percent of the pendulum group and 70% of the bubble group had rotation error ≤3 (P=0.589), and 90% eyes of the pendulum group and 96.7% of the bubble group had rotation error ≤5 (P=0.612). CONCLUSION Both preoperative marking techniques result in approximately 3 of alignment error. Both marking techniques are simple, predictable, reproducible and easy to perform. PMID:27275425
Invisible marker based augmented reality system
NASA Astrophysics Data System (ADS)
Park, Hanhoon; Park, Jong-Il
2005-07-01
Augmented reality (AR) has recently gained significant attention. The previous AR techniques usually need a fiducial marker with known geometry or objects of which the structure can be easily estimated such as cube. Placing a marker in the workspace of the user can be intrusive. To overcome this limitation, we present an AR system using invisible markers which are created/drawn with an infrared (IR) fluorescent pen. Two cameras are used: an IR camera and a visible camera, which are positioned in each side of a cold mirror so that their optical centers coincide with each other. We track the invisible markers using IR camera and visualize AR in the view of visible camera. Additional algorithms are employed for the system to have a reliable performance in the cluttered background. Experimental results are given to demonstrate the viability of the proposed system. As an application of the proposed system, the invisible marker can act as a Vision-Based Identity and Geometry (VBIG) tag, which can significantly extend the functionality of RFID. The invisible tag is the same as RFID in that it is not perceivable while more powerful in that the tag information can be presented to the user by direct projection using a mobile projector or by visualizing AR on the screen of mobile PDA.
Marker-Assisted Introgression in Backcross Breeding Programs
Visscher, P. M.; Haley, C. S.; Thompson, R.
1996-01-01
The efficiency of marker-assisted introgression in backcross populations derived from inbred lines was investigated by simulation. Background genotypes were simulated assuming that a genetic model of many genes of small effects in coupling phase explains the observed breed difference and variance in backcross populations. Markers were efficient in introgression backcross programs for simultaneously introgressing an allele and selecting for the desired genomic background. Using a marker spacing of 10-20 cM gave an advantage of one to two backcross generations selection relative to random or phenotypic selection. When the position of the gene to be introgressed is uncertain, for example because its position was estimated from a trait gene mapping experiment, a chromosome segment should be introgressed that is likely to include the allele of interest. Even for relatively precisely mapped quantitative trait loci, flanking markers or marker haplotypes should cover ~10-20 cM around the estimated position of the gene, to ensure that the allele frequency does not decline in later backcross generations. PMID:8978075
Assessing Date Palm Genetic Diversity Using Different Molecular Markers.
Atia, Mohamed A M; Sakr, Mahmoud M; Adawy, Sami S
2017-01-01
Molecular marker technologies which rely on DNA analysis provide powerful tools to assess biodiversity at different levels, i.e., among and within species. A range of different molecular marker techniques have been developed and extensively applied for detecting variability in date palm at the DNA level. Recently, the employment of gene-targeting molecular marker approaches to study biodiversity and genetic variations in many plant species has increased the attention of researchers interested in date palm to carry out phylogenetic studies using these novel marker systems. Molecular markers are good indicators of genetic distances among accessions, because DNA-based markers are neutral in the face of selection. Here we describe the employment of multidisciplinary molecular marker approaches: amplified fragment length polymorphism (AFLP), start codon targeted (SCoT) polymorphism, conserved DNA-derived polymorphism (CDDP), intron-targeted amplified polymorphism (ITAP), simple sequence repeats (SSR), and random amplified polymorphic DNA (RAPD) to assess genetic diversity in date palm.
Detection of immunocytological markers in photomicroscopic images
NASA Astrophysics Data System (ADS)
Friedrich, David; zur Jacobsmühlen, Joschka; Braunschweig, Till; Bell, André; Chaisaowong, Kraisorn; Knüchel-Clarke, Ruth; Aach, Til
2012-03-01
Early detection of cervical cancer can be achieved through visual analysis of cell anomalies. The established PAP smear achieves a sensitivity of 50-90%, most false negative results are caused by mistakes in the preparation of the specimen or reader variability in the subjective, visual investigation. Since cervical cancer is caused by human papillomavirus (HPV), the detection of HPV-infected cells opens new perspectives for screening of precancerous abnormalities. Immunocytochemical preparation marks HPV-positive cells in brush smears of the cervix with high sensitivity and specificity. The goal of this work is the automated detection of all marker-positive cells in microscopic images of a sample slide stained with an immunocytochemical marker. A color separation technique is used to estimate the concentrations of the immunocytochemical marker stain as well as of the counterstain used to color the nuclei. Segmentation methods based on Otsu's threshold selection method and Mean Shift are adapted to the task of segmenting marker-positive cells and their nuclei. The best detection performance of single marker-positive cells was achieved with the adapted thresholding method with a sensitivity of 95.9%. The contours differed by a modified Hausdorff Distance (MHD) of 2.8 μm. Nuclei of single marker positive cells were detected with a sensitivity of 95.9% and MHD = 1.02 μm.
Inflammatory Markers and Preeclampsia: A Systematic Review.
Black, Kathleen Darrah; Horowitz, June Andrews
Preeclampsia (PE), a serious and variable pregnancy complication affecting 5%-10% of the obstetric population, has an undetermined etiology, yet inflammation is concomitant with its development, particularly in relation to endothelial dysfunction. The purpose of this systematic review was to examine the published evidence concerning an association between PE and inflammatory markers for their usefulness in the prediction or early identification of women with PE in antepartum clinical settings. In this systematic review, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cumulative Index for Nursing and Allied Health and MEDLINE/OVID were the electronic databases used for identifying published articles. We placed no time limit on the publication year. The search generated 798 articles. After removing duplicates, screening abstracts, and conducting full-text reviews, we retained 73 articles and examined 57 unique markers. This review shows that C-reactive protein and the cytokines, specifically the proinflammatory markers IL-6, IL-8, and tumor necrosis factor alpha, garner the most support as potential inflammatory markers for clinical surveillance of PE, particularly during the second and third trimesters. Based on this review, we cannot recommend any single inflammatory marker for routine clinical use to predict/identify PE onset or progression. Research is recommended to examine a combination panel of these four inflammatory markers both with and without clinical risk factors toward the goal of translation to practice.
Cell-surface markers for colon adenoma and adenocarcinoma
Sewda, Kamini; Coppola, Domenico; Enkemann, Steven; Yue, Binglin; Kim, Jongphil; Lopez, Alexis S.; Wojtkowiak, Jonathan W.; Stark, Valerie E.; Morse, Brian; Shibata, David; Vignesh, Shivakumar; Morse, David L.
2016-01-01
Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC. PMID:26894861
Cell-surface markers for colon adenoma and adenocarcinoma.
Sewda, Kamini; Coppola, Domenico; Enkemann, Steven; Yue, Binglin; Kim, Jongphil; Lopez, Alexis S; Wojtkowiak, Jonathan W; Stark, Valerie E; Morse, Brian; Shibata, David; Vignesh, Shivakumar; Morse, David L
2016-04-05
Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.
Zhao, Hansheng; Yang, Li; Peng, Zhenhua; Sun, Huayu; Yue, Xianghua; Lou, Yongfeng; Dong, Lili; Wang, Lili; Gao, Zhimin
2015-01-26
Morphology-based taxonomy via exiguously reproductive organ has severely limitation on bamboo taxonomy, mainly owing to infrequent and unpredictable flowering events of bamboo. Here, we present the first genome-wide analysis and application of microsatellites based on the genome of moso bamboo (Phyllostachys edulis) to assist bamboo taxonomy. Of identified 127,593 microsatellite repeat-motifs, the primers of 1,451 microsatellites were designed and 1,098 markers were physically mapped on the genome of moso bamboo. A total of 917 markers were successfully validated in 9 accessions with ~39.8% polymorphic potential. Retrieved from validated microsatellite markers, 23 markers were selected for polymorphic analysis among 78 accessions and 64 alleles were detected with an average of 2.78 alleles per primers. The cluster result indicated the majority of the accessions were consistent with their current taxonomic classification, confirming the suitability and effectiveness of the developed microsatellite markers. The variations of microsatellite marker in different species were confirmed by sequencing and in silico comparative genome mapping were investigated. Lastly, a bamboo microsatellites database (http://www.bamboogdb.org/ssr) was implemented to browse and search large information of bamboo microsatellites. Consequently, our results of microsatellite marker development are valuable for assisting bamboo taxonomy and investigating genomic studies in bamboo and related grass species.
Markers and mapping revisited: finding your gene.
Jones, Neil; Ougham, Helen; Thomas, Howard; Pasakinskiene, Izolda
2009-01-01
This paper is an update of our earlier review (Jones et al., 1997, Markers and mapping: we are all geneticists now. New Phytologist 137: 165-177), which dealt with the genetics of mapping, in terms of recombination as the basis of the procedure, and covered some of the first generation of markers, including restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNA (RAPDs), simple sequence repeats (SSRs) and quantitative trait loci (QTLs). In the intervening decade there have been numerous developments in marker science with many new systems becoming available, which are herein described: cleavage amplification polymorphism (CAP), sequence-specific amplification polymorphism (S-SAP), inter-simple sequence repeat (ISSR), sequence tagged site (STS), sequence characterized amplification region (SCAR), selective amplification of microsatellite polymorphic loci (SAMPL), single nucleotide polymorphism (SNP), expressed sequence tag (EST), sequence-related amplified polymorphism (SRAP), target region amplification polymorphism (TRAP), microarrays, diversity arrays technology (DArT), single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE) and methylation-sensitive PCR. In addition there has been an explosion of knowledge and databases in the area of genomics and bioinformatics. The number of flowering plant ESTs is c. 19 million and counting, with all the opportunity that this provides for gene-hunting, while the survey of bioinformatics and computer resources points to a rapid growth point for future activities in unravelling and applying the burst of new information on plant genomes. A case study is presented on tracking down a specific gene (stay-green (SGR), a post-transcriptional senescence regulator) using the full suite of mapping tools and comparative mapping resources. We end with a brief speculation on how genome analysis may progress into the future of
Virulence Markers of Dengue Viruses
1990-02-20
of dengue viruses . We initially evaluated onocye-infectivity as a marker the for virulence of dengue-2 virus by testing 72 dengue-2 viral isolates...infectivity can be used as a virulence marker for dengue viruses . For this purpose, virulence is defined as the intrinsic ability of the virus to...but not dengue-1 and -3 viruses Table 5. Comparison of infectivity of dengue-2 virus in K-562 28 monocytes and viral monocyte infectivity index derived
Razmjou, Sahar; Abdulnour, Joseph; Bastard, Jean-Philippe; Fellahi, Soraya; Doucet, Éric; Brochu, Martin; Lavoie, Jean-Marc; Rabasa-Lhoret, Rémi; Prud'homme, Denis
2018-01-01
Menopausal transition and postmenopause are usually associated with changes in body composition and a decrease in physical activity energy expenditure (PAEE). This study investigated body composition, cardiometabolic risk factors, PAEE, and inflammatory markers in premenopausal women after a 10-year follow-up. In all, 102 premenopausal women participated in the 5-year observational longitudinal Montreal Ottawa New Emerging Team (MONET) study. This present substudy included 48 participants (age: 60.0 ± 1.7 years; body mass index: 23.2 ± 2.2 kg/m) 6.0 ± 0.3 years after completion of the initial MONET study. Measures included body composition, waist circumference (WC), fasting glucose and insulin levels, insulin sensitivity (QUICKI model), plasma lipid levels, PAEE, and inflammatory markers. Compared with baseline measures of the MONET study, analyses revealed no significant increase in body weight, although there were significant increases in WC, fat mass (FM), % FM, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, haptoglobin, apolipoprotein B, ferritin, adiponectin, and soluble cluster of differentiation 14 (all P < 0.001) after the 10-year follow-up. However, significant decreases were observed for fat-free mass, PAEE, fasting glucose levels, interleukin-8 levels, and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2) levels (all P < 0.05). To determine the effect of postmenopausal years, data were restructured based on final menstrual period (FMP), and one-way analyses of variance were performed.Waist circumference, % FM, total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, ferritin, adiponectin, and soluble cluster of differentiation 14 were higher in early and late postmenopausal periods in these women. sTNFR-1 and sTNFR-2 levels were higher at the FMP and early postmenopausal years as compared with the late postmenopausal periods. Finally
Monte Carlo simulations on marker grouping and ordering.
Wu, J; Jenkins, J; Zhu, J; McCarty, J; Watson, C
2003-08-01
Four global algorithms, maximum likelihood (ML), sum of adjacent LOD score (SALOD), sum of adjacent recombinant fractions (SARF) and product of adjacent recombinant fraction (PARF), and one approximation algorithm, seriation (SER), were used to compare the marker ordering efficiencies for correctly given linkage groups based on doubled haploid (DH) populations. The Monte Carlo simulation results indicated the marker ordering powers for the five methods were almost identical. High correlation coefficients were greater than 0.99 between grouping power and ordering power, indicating that all these methods for marker ordering were reliable. Therefore, the main problem for linkage analysis was how to improve the grouping power. Since the SER approach provided the advantage of speed without losing ordering power, this approach was used for detailed simulations. For more generality, multiple linkage groups were employed, and population size, linkage cutoff criterion, marker spacing pattern (even or uneven), and marker spacing distance (close or loose) were considered for obtaining acceptable grouping powers. Simulation results indicated that the grouping power was related to population size, marker spacing distance, and cutoff criterion. Generally, a large population size provided higher grouping power than small population size, and closely linked markers provided higher grouping power than loosely linked markers. The cutoff criterion range for achieving acceptable grouping power and ordering power differed for varying cases; however, combining all situations in this study, a cutoff criterion ranging from 50 cM to 60 cM was recommended for achieving acceptable grouping power and ordering power for different cases.
Serum biochemical markers in lung cancer.
Burt, R. W.; Ratcliffe, J. G.; Stack, B. H.; Cuthbert, J.; Kennedy, R. S.; Corker, C. S.; Franchimont, P.; Spilg, W. G.; Stimson, W. H.
1978-01-01
The prevalence of elevated serum levels of 5 potential tumour-associated antigens was determined in patients with lung cancer sampled at the time of initial presentation, using age- and sex-matched patients with benign lung disease as controls. Elevated levels (greater than upper 95th centile of controls) were found as follows: carcinoembryonic antigen (CEA), 17%; pregnancy-associated alpha-macroglobulin (PAM), 16%; casein 14%; human chorionic gonadotrophin (HCG) 6%; alpha-foetoprotein (AFP), 1.5%. The prevalence of elevated CEA levels (but not other markers) was higher in patients with evidence of extra-thoracic tumour spread (23%) mainly due to anaplastic tumours and adenocarcinomas. A degree of concordance of elevated marker levels occurred with CEA, HCG, casein and AFP, but there was a striking discordance of elevated CEA and PAM levels. Simultaneous assays of CEA and PAM will detect the majority of patients with elevations of any of the markers studied, and are likely to be the most useful biochemical markers in following the response of lung tumours to therapy. PMID:77672
USDA-ARS?s Scientific Manuscript database
Pomegranate (Punica granatum L.) is one of the oldest known edible fruits and more and more it arouse interest of scientific community given its numerous biological activities. However, information about its genetic resources and characterization using reliable molecular markers are still scarce. In...
Marker optimization for facial motion acquisition and deformation.
Le, Binh H; Zhu, Mingyang; Deng, Zhigang
2013-11-01
A long-standing problem in marker-based facial motion capture is what are the optimal facial mocap marker layouts. Despite its wide range of potential applications, this problem has not yet been systematically explored to date. This paper describes an approach to compute optimized marker layouts for facial motion acquisition as optimization of characteristic control points from a set of high-resolution, ground-truth facial mesh sequences. Specifically, the thin-shell linear deformation model is imposed onto the example pose reconstruction process via optional hard constraints such as symmetry and multiresolution constraints. Through our experiments and comparisons, we validate the effectiveness, robustness, and accuracy of our approach. Besides guiding minimal yet effective placement of facial mocap markers, we also describe and demonstrate its two selected applications: marker-based facial mesh skinning and multiresolution facial performance capture.
Tan, Darrell H S; Raboud, Janet M; Szadkowski, Leah; Yi, Tae Joon; Shannon, Brett; Kaul, Rupert; Liles, W Conrad; Walmsley, Sharon L
2015-03-01
Systemic inflammation and immune activation may persist in HIV-infected persons on suppressive combination antiretroviral therapy (cART) and contribute to adverse health outcomes. We compared markers of immune activation, inflammation, and abnormal glucose and lipid metabolism in HIV-infected adults according to herpes simplex virus type 2 (HSV-2) serostatus in a 6-month observational cohort study in Toronto, Canada. HIV-infected adults on suppressive (viral load <50 copies/ml) cART were categorized as HSV-2 seropositive or seronegative using the HerpeSelect ELISA, and underwent study visits at baseline, 3 months, and 6 months. The primary outcome was the median percentage of activated (CD38(+)HLADR(+)) CD8 T cells. Secondary outcome measures included additional immune (activated CD4, regulatory T cells) and inflammatory (hsCRP, D-dimer, IL-1b, IL-6, MCP-1, TNF, sICAM-1, sVCAM-1, Ang1/Ang2 ratio) markers. Metabolic outcomes included the proportion with impaired fasting glucose/impaired glucose tolerance/diabetes, insulin sensitivity (calculated using the Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and fasting lipids. The impact of HSV-2 on each outcome was estimated using generalized estimating equation regression models. Of 84 participants, 38 (45%) were HSV-2 seropositive. HSV signs and symptoms were uncommon. Aside from D-dimer, which was more often detectable in HSV-2 seropositives (adjusted odds ratio=3.58, 95% CI=1.27, 10.07), HSV-2 serostatus was not associated with differences in any other immune, inflammatory cytokine, acute phase reactant, endothelial activation, or metabolic markers examined in univariable or multivariable models. During the study, CD8 and CD4 T cell activation declined by 0.16% and 0.08% per month, respectively, while regulatory T cells increased by 0.05% per month. HSV-2 serostatus was not consistently associated with immune activation, inflammatory, or lipid and glucose metabolic markers in
Suzuki, M; Desmond, T J; Albin, R L; Frey, K A
2001-09-15
Markers of identified neuronal populations have previously suggested selective degeneration of projection neurons in Huntington's disease (HD) striatum. Interpretations are, however, limited by effects of compensatory regulation and atrophy. Studies of the vesicular monoamine transporter type-2 (VMAT2) and of the vesicular acetylcholine transporter (VAChT) in experimental animals indicate that they are robust markers of presynaptic integrity and are not subject to regulation. We measured dopamine and acetylcholine vesicular transporters to characterize the selectivity of degeneration in HD striatum. Brains were obtained at autopsy from four HD patients and five controls. Autoradiography was used to quantify radioligand binding to VMAT2, VAChT, the dopamine plasmalemmal transporter (DAT), benzodiazepine (BZ) binding sites, and D2-type dopamine receptors. The activity of choline acetyltransferase (ChAT) was determined as an additional marker of cholinergic neurons. Autoradiograms were analyzed by video-assisted densitometry and assessment of atrophy was made from regional structural areas in the coronal projection. Striatal VMAT2, DAT, and VAChT concentrations were unchanged or increased, while D2 and BZ binding and ChAT activity were decreased in HD. After atrophy correction, all striatal binding sites were decreased. However, the decrease in ChAT activity was 3-fold greater than that of VAChT binding. In addition to degeneration of striatal projection neurons, there are losses of extrinsic nigrostriatal projections and of striatal cholinergic interneurons in HD on the basis of vesicular transporter measures. There is also markedly reduced expression of ChAT by surviving cholinergic striatal interneurons. Copyright 2001 Wiley-Liss, Inc.
Mier-Cabrera, Jennifer; Aburto-Soto, Tania; Burrola-Méndez, Soraya; Jiménez-Zamudio, Luis; Tolentino, Mari C; Casanueva, Esther; Hernández-Guerrero, César
2009-01-01
Background Oxidative stress has been identified in the peritoneal fluid and peripheral blood of women with endometriosis. However, there is little information on the antioxidant intake for this group of women. The objectives of this work were 1) to compare the antioxidant intake among women with and without endometriosis and 2) to design and apply a high antioxidant diet to evaluate its capacity to reduce oxidative stress markers and improve antioxidant markers in the peripheral blood of women with endometriosis. Methods Women with (WEN, n = 83) and without endometriosis (WWE, n = 80) were interviewed using a Food Frequency Questionnaire to compare their antioxidant intake (of vitamins and minerals). Then, the WEN participated in the application of a control (n = 35) and high antioxidant diet (n = 37) for four months. The high antioxidant diet (HAD) guaranteed the intake of 150% of the suggested daily intake of vitamin A (1050 μg retinol equivalents), 660% of the recommended daily intake (RDI) of vitamin C (500 mg) and 133% of the RDI of vitamin E (20 mg). Oxidative stress and antioxidant markers (vitamins and antioxidant enzymatic activity) were determined in plasma every month. Results Comparison of antioxidant intake between WWE and WEN showed a lower intake of vitamins A, C, E, zinc, and copper by WEN (p < 0.05, Mann Whitney Rank test). The selenium intake was not statistically different between groups. During the study, the comparison of the 24-hour recalls between groups showed a higher intake of the three vitamins in the HAD group. An increase in the vitamin concentrations (serum retinol, alpha-tocopherol, leukocyte and plasma ascorbate) and antioxidant enzyme activity (superoxide dismutase and glutathione peroxidase) as well as a decrease in oxidative stress markers (malondialdehyde and lipid hydroperoxides) were observed in the HAD group after two months of intervention. These phenomena were not observed in the control group. Conclusion WEN had a lower
Cropley, Vanessa; Wood, Stephen J; Pantelis, Christos
2013-05-10
Schizophrenia is a debilitating illness that is often associated with progressive clinical deterioration following repeated episodes of illness. Despite the clinical evidence for clinical attrition, the nature of any associated neurobiological pathology has not been examined systematically. This review examines the neurobiological imaging markers associated with psychosis onset and relapse and considers whether these may be potential state markers of acute psychosis. We report several markers of neurobiological changes associated with acute psychosis. These include dynamic changes in brain structure in the frontal and temporal regions, neurochemical alterations in dopamine and glutamate and evidence for neuroinflammation through microglial activation. We propose that with the use of repeat longitudinal assessments of brain imaging markers over the course of a psychosis relapse, the neurobiological trajectory indicative of a 'relapse signature' for psychosis will be identified.
ERIC Educational Resources Information Center
Shriberg, Lawrence D.; Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.
2017-01-01
Purpose: Three previous articles provided rationale, methods, and several forms of validity support for a diagnostic marker of childhood apraxia of speech (CAS), termed the pause marker (PM). Goals of the present article were to assess the validity and stability of the PM Index (PMI) to scale CAS severity. Method: PM scores and speech, prosody,…
Using dynamic programming to improve fiducial marker localization
NASA Astrophysics Data System (ADS)
Wan, Hanlin; Ge, Jiajia; Parikh, Parag
2014-04-01
Fiducial markers are used in a wide range of medical imaging applications. In radiation therapy, they are often implanted near tumors and used as motion surrogates that are tracked with fluoroscopy. We propose a novel and robust method based on dynamic programming (DP) for retrospectively localizing radiopaque fiducial markers in fluoroscopic images. Our method was compared to template matching (TM) algorithms on 407 data sets from 24 patients. We found that the performance of TM varied dramatically depending on the template used (ranging from 47% to 92% of data sets with a mean error <1 mm). DP by itself requires no template and performed as well as the best TM method, localizing the markers in 91% of the data sets with a mean error <1 mm. Finally, by combining DP and TM, we were able to localize the markers in 99% of the data sets with a mean error <1 mm, regardless of the template used. Our results show that DP can be a powerful tool for analyzing tumor motion, capable of accurately locating fiducial markers in fluoroscopic images regardless of marker type, shape, and size.
Implication of Gastric Cancer Molecular Genetic Markers in Surgical Practice.
Nemtsova, Marina V; Strelnikov, Vladimir V; Tanas, Alexander S; Bykov, Igor I; Zaletaev, Dmitry V; Rudenko, Viktoria V; Glukhov, Alexander I; Kchorobrich, Tatiana V; Li, Yi; Tarasov, Vadim V; Barreto, George E; Aliev, Gjumrakch
2017-10-01
We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied. The selected parameters comprise a system of molecular markers that can be used in both diagnostics of gastric cancer and in dynamic monitoring of patients after surgery. Special attention was paid to the use of molecular markers for the diagnostics of malignant process in the material obtained endoscopically since the efficacy of morphological diagnostics in biopsies is compromised by intratumoral heterogeneity, which may prevent reliable identification of tumor cells in the sampling. Our data indicated that certain molecular genetic events provided more sensitive yet specific markers of the tumor. We demonstrated that molecular profiles detected in preoperative biopsies were confirmed by the material obtained intra-operatively. The use of endoscopic material facilitates gastric tumors pre-operative diagnostics, improving early detection of gastric cancer and potential effective treatment strategies.
Overexpression of hypoxia/inflammatory markers in atherosclerotic carotid plaques.
Luque, Ana; Turu, Marta; Juan-Babot, Oriol; Cardona, Pere; Font, Angels; Carvajal, Ana; Slevin, Mark; Iborra, Elena; Rubio, Francisco; Badimon, Lina; Krupinski, Jerzy
2008-05-01
Hypoxia, angiogenesis and inflammation leads to plaque progression and remodelling and may significantly contribute towards plaque rupture and subsequent cerebrovascular events. Our aim was to study, markers of hypoxia and inflammation previously identified by microarray analysis, in atherosclerotic carotid arteries with low to moderate stenosis. We hoped to describe different cellular populations expressing the studied markers. The location of selected inflammatory molecules obtained as vascular transplants from organ donors were analysed by immunohistochemistry with monoclonal and polyclonal antibodies. Paraffin-embedded sections were cut and probed with antibodies recognizing active B and T-lymphocytes (CD30), hypoxia-inducible factor-1alpha, endoglin (CD105), Interleukin-6 and C-reactive protein. We observed a notable overexpression of HIF-1alpha in inflammatory and hypoxic areas of carotid arteries in all types of lesions from type II-V taken from the patients with carotid stenosis less than 50%. This suggests that HIF-1alpha may have a putative role in atherosclerosis progression and angiogenesis. Dynamic changes in the non-occluding plaques may explain some of the clinical events in patients with low to moderate carotid stenosis.
A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
Ariey, Frédéric; Witkowski, Benoit; Amaratunga, Chanaki; Beghain, Johann; Langlois, Anne-Claire; Khim, Nimol; Kim, Saorin; Duru, Valentine; Bouchier, Christiane; Ma, Laurence; Lim, Pharath; Leang, Rithea; Duong, Socheat; Sreng, Sokunthea; Suon, Seila; Chuor, Char Meng; Bout, Denis Mey; Ménard, Sandie; Rogers, William O.; Genton, Blaise; Fandeur, Thierry; Miotto, Olivo; Ringwald, Pascal; Le Bras, Jacques; Berry, Antoine; Barale, Jean-Christophe; Fairhurst, Rick M.; Benoit-Vical, Françoise; Mercereau-Puijalon, Odile; Ménard, Didier
2016-01-01
Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain (‘K13-propeller’) with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread. PMID:24352242
Labouesse, Marie A.; Gertz, Erik R.; Piccolo, Brian D.; Souza, Elaine C.; Schuster, Gertrud U.; Witbracht, Megan G.; Woodhouse, Leslie R.; Adams, Sean H.; Keim, Nancy L.; Van Loan, Marta D.
2015-01-01
INTRODUCTION Weight loss reduces co-morbidities of obesity, but decreases bone mass. PURPOSE Our aims were to 1) determine if adequate dairy intake attenuates weight loss-induced bone loss; 2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; 3) model the contribution of these variables to post weight-loss BMD and BMC METHODS Overweight/obese women (BMI: 28–37 kg/m2) were enrolled in an energy reduced (−500 kcal/d; −2092 kJ/d) diet with adequate dairy (AD: 3–4 servings/d; n=25, 32.2 ± 8.8y) or low dairy (LD: ≤ 1 serving/d; n=26, 31.7 ± 8.4 y). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. RESULTS Following weight loss, AD intake resulted in significantly greater (p= 0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post- body fat were negatively associated with hip and lumbar spine BMC (r= −0.28, p=0.04 to −0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = −0.29 (p=0.04) to r = −0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss Factors. Pre-weight loss Factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss Factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the Factors contributed to the variance in lumbar spine BMD. CONCLUSION AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD
Clay, MR.; Tabor, M.; Owen, J.; Carey, TE.; Bradford, CR.; Wolf, GT.; Wicha, MS.; Prince, ME.
2010-01-01
Background According to the cancer stem cell (CSC) theory only a small subset of cancer cells are capable of forming tumors. We previously reported that CD44 isolates tumorigenic cells from HNSCC. Recent studies indicate that aldehyde dehydrogenase (ALDH) activity may represent a more specific marker of CSCs. Methods Six primary HNSCC were collected. Cells with high and low ALDH activity (ALDHhigh/ALDHlow) were isolated. ALDHhigh and ALDHlow populations were implanted into NOD/SCID mice and monitored for tumor development. Results ALDHhigh cells represented a small percentage of the tumor cells (1-7.8%). ALDHhigh cells formed tumors from as few as 500 cells in 24/45 implantations while only 3/37 implantations of ALDHlow cells formed tumors. Conclusions ALDHhigh cells comprise a subpopulation cells in HNSCC that are tumorigenic and capable of producing tumors at very low numbers. This finding indicates that ALDH activity on its own is a highly selective marker for CSCs in HNSCC. PMID:20073073
Age-related Decline in Case-Marker Processing and its Relation to Working Memory Capacity.
Sung, Jee Eun
2017-09-01
Purposes of the current study were to investigate whether age-related decline emerged in a case-marker assignment task (CMAT) and to explore the relationship between working-memory (WM) capacity and case-marker processing. A total of 121 individuals participated in the study with 62 younger adults and 59 elderly adults. All were administered a CMAT that consisted of active and passive constructions with canonical and noncanonical word-order conditions. A composite measure of WM tasks served as an index of participants' WM capacity. The older group performed worse than the younger group, and the noncanonical word order elicited worse performance than the canonical condition. The older group demonstrated greater difficulty in case-marker processing under the canonical condition and passive construction. Regression results revealed that age, education, and sentence type were the best predictors to account for performance on the CMAT. The canonicity of word order and passive construction were critical factors related to decline in abilities in a case-marker assignment. The combination of age, education, and sentence type factors accounted for overall performance on case-marker processing. Results indicated the crucial necessity to find a cognitively and linguistically demanding condition that elicits aging effects most efficiently, considering language-specific syntactic features. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas
Azuma, Sakiko; Yokoyama, Yukihiro; Yamamoto, Akiko; Kyokane, Kazuhiro; Niida, Shumpei; Ishiguro, Hiroshi; Ko, Minoru S. H.
2013-01-01
We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4+) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4+ cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4+ cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas. PMID:23599043
Antolič, Bor; Pernat, Andrej; Cvijić, Marta; Žižek, David; Jan, Matevž; Šinkovec, Matjaž
2016-07-01
Evidence from animal and human studies suggests that cryoablation might be associated with a lesser inflammatory response and activation of coagulation compared with radiofrequency ablation. The study was aimed at comparing the effect of cryoballoon and radiofrequency catheter ablation of paroxysmal atrial fibrillation on markers of myocardial damage, inflammation, and activation of coagulation. Forty-one patients received either cryoballoon (n = 23) or radiofrequency (n = 18) ablation of atrial fibrillation. We measured troponin I, high-sensitivity CRP, and interleukin 6 at baseline from the cubital vein, and from the right and left atrium before and after ablation, and from the cubital vein the following day. Prothrombin fragments 1 + 2, soluble P‑selectin, and D‑dimer were measured before and after ablation from both atria. We observed higher troponin I release in the cryoballoon than in the radiofrequency group (7.01 mcg/l (interquartile range [IQR]: 5.30-9.09) vs 2.32 mcg/l (IQR: 1.45-2.98), p < 0.001). The levels of inflammatory markers (high-sensitivity CRP and interleukin 6) in the two groups were comparable, as were the levels of markers of coagulation activation. Procedure duration, fluoroscopy times, and mid-term success (23 months, IQR 7-32) of the two groups were also comparable. Cryoballoon ablation of atrial fibrillation causes more significant myocardial damage, that is, more extensive ablation lesions, compared with radiofrequency catheter ablation. However, no major differences between these two ablation techniques with regard to the inflammatory response and activation of the coagulation system were observed.
Schievenbusch, Stephanie; Sauer, Elisabeth; Curth, Harald-Morten; Schulte, Sigrid; Demir, Münevver; Toex, Ulrich; Goeser, Tobias; Nierhoff, Dirk
2012-09-20
We have previously identified Neighbor of Punc E 11 (Nope) as a specific cell surface marker of stem/progenitor cells in the murine fetal liver that is also expressed in hepatocellular carcinoma. Here, we focus on the differential expression pattern of Nope during murine fetal and postnatal liver development as well as in a normal and regenerating adult liver including oval cell activation. In the fetal liver, Nope shows a constantly high expression level and is a useful surface marker for the identification of Dlk, E-cadherin, and CD133-positive hepatoblasts by flow cytometry. Postnatally, Nope expression declines rapidly and remains barely detectable in the adult liver as shown by quantitative real-time reverse-transcriptase polymerase chain reaction and western blot analyses. Immunohistochemically, costainings for Nope- and epithelial-specific markers (E-cadherin), markers of early hepatoblasts (alpha-fetoprotein), and biliary marker proteins (CK19) demonstrate that Nope is initially expressed on bipotent hepatoblasts and persists thereafter on commited hepatocytic as well as cholangiocytic progenitor cells during late fetal liver development. Postnatally, Nope loses its circular expression pattern and is specifically directed to the sinusoidal membrane of early hepatocytes. While Nope is only weakly expressed on cholangiocytes in the normal adult liver, activated stem/progenitor (oval) cells clearly coexpress Nope together with the common markers A6, EpCAM, and CD24 in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model. In conclusion, Nope should be most useful in future research to define the differentiation stage of hepatic-specified cells of various sources and is a promising candidate to identify and isolate hepatic stem cells from the adult liver.
Development of microsatellite markers in Parthenium ssp.
USDA-ARS?s Scientific Manuscript database
Molecular markers provide the most efficient means to study genetic diversity within and among species of a particular genus. In addition, molecular markers can facilitate breeding efforts by providing tools necessary to reduce the time required to obtain recombinant genotypes with improved agricu...
Measuring job stress among hospital nurses: an attempt to identify biological markers.
Kawaguchi, Yoshichika; Toyomasu, Kouji; Yoshida, Noriko; Baba, Kaori; Uemoto, Masaharu; Minota, Shoichi
2007-02-01
The purpose of this study was to identify biological markers corresponding to job stress among hospital nurses. The subjects of this study were 128 nurses working at a university hospital. The NIOSH job stress questionnaire and the Miki Nurse Stressor 35-item Scale measured their job stress levels. The GHQ28 was also used to measure the subjects' general mental health status. Blood analyses for neuroendocrine function and immunity reaction were performed in order to identify biological markers of job stress. Stress is related to the plasma levels of catecholamine, cortisol, adrenocorticotrophic hormone, and natural killer cell activity, therefore these factors were measured accordingly. In consideration to circadian rhythms, blood was collected from the subjects prior to the start of the day shift. The nurses filled out the questionnaires on the day of the blood tests. In order to investigate the correlation between job stress reactions indicated by the questionnaires and the results of the blood tests, we utilized Pearson's correlation coefficient and partial correlation coefficient for which other affected items were controlled. In this study, significant correlations were found between job stress and biological factors; however, the correlations were not strong. Thus, it can be said that the biological markers associated with a specific kind of job stress remain unclear. In the future, rather than implementing a simple cross-sectional study, a longitudinal study including follow-up research will be more effective in establishing biological markers for job stress.
Molecular markers of neuropsychological functioning and Alzheimer's disease.
Edwards, Melissa; Balldin, Valerie Hobson; Hall, James; O'Bryant, Sid
2015-03-01
The current project sought to examine molecular markers of neuropsychological functioning among elders with and without Alzheimer's disease (AD) and determine the predictive ability of combined molecular markers and select neuropsychological tests in detecting disease presence. Data were analyzed from 300 participants (n = 150, AD and n = 150, controls) enrolled in the Texas Alzheimer's Research and Care Consortium. Linear regression models were created to examine the link between the top five molecular markers from our AD blood profile and neuropsychological test scores. Logistical regressions were used to predict AD presence using serum biomarkers in combination with select neuropsychological measures. Using the neuropsychological test with the least amount of variance overlap with the molecular markers, the combined neuropsychological test and molecular markers was highly accurate in detecting AD presence. This work provides the foundation for the generation of a point-of-care device that can be used to screen for AD.
Novel prognostic tissue markers in congestive heart failure.
Stone, James R
2015-01-01
Heart failure is a relatively common disorder associated with high morbidity, mortality, and economic burden. Better tools to predict outcomes for patients with heart failure could allow for better decision making concerning patient treatment and management and better utilization of health care resources. Endomyocardial biopsy offers a mechanism to pathologically diagnose specific diseases in patients with heart failure, but such biopsies can often be negative, with no specific diagnostic information. Novel tissue markers in endomyocardial biopsies have been identified that may be useful in assessing prognosis in heart failure patients. Such tissue markers include ubiquitin, Gremlin-1, cyclophilin A, and heterogeneous nuclear ribonucleoprotein C. In some cases, tissue markers have been found to be independent of and even superior to clinical indices and serum markers in predicting prognosis for heart failure patients. In some cases, these novel tissue markers appear to offer prognostic information even in the setting of an otherwise negative endomyocardial biopsy. Copyright © 2014 Elsevier Inc. All rights reserved.
Bone turnover marker reference intervals in young females.
Callegari, Emma T; Gorelik, Alexandra; Garland, Suzanne M; Chiang, Cherie Y; Wark, John D
2017-07-01
Background The use of bone turnover markers in clinical practice and research in younger people is limited by the lack of normative data and understanding of common causes of variation in bone turnover marker values in this demographic. To appropriately interpret bone turnover markers, robust reference intervals specific to age, development and sex are necessary. This study aimed to determine reference intervals of bone turnover markers in females aged 16-25 years participating in the Safe-D study. Methods Participants were recruited through social networking site Facebook and were asked to complete an extensive, online questionnaire and attend a site visit. Participants were tested for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and total procollagen type 1 N-propeptide using the Roche Elecsys automated analyser. Reference intervals were determined using the 2.5th to 97.5th percentiles of normalized bone turnover marker values. Results Of 406 participants, 149 were excluded due to medical conditions or medication use (except hormonal contraception) which may affect bone metabolism. In the remaining 257 participants, the reference interval was 230-1000 ng/L for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and 27-131 µg/L for procollagen type 1 N-propeptide. Both marker concentrations were inversely correlated with age and oral contraceptive pill use. Therefore, intervals specific to these variables were calculated. Conclusions We defined robust reference intervals for cross-linking telopeptide of type 1 collagen and procollagen type 1 N-propeptide in young females grouped by age and contraceptive pill use. We examined bone turnover markers' relationship with several lifestyle, clinical and demographic factors. Our normative intervals should aid interpretation of bone turnover markers in young females particularly in those aged 16 to 19 years where reference intervals are currently provisional.
NASA Astrophysics Data System (ADS)
Wilkinson, Timothy; Clarkson, John; White, Peter C.; Meakin, Nicholas; McDonald, Ken
2013-05-01
Governments often tax fuel products to generate revenues to support and stimulate their economies. They also subsidize the cost of essential fuel products. Fuel taxation and subsidization practices are both subject to fraud. Oil marketing companies also suffer from fuel fraud with loss of legitimate sales and additional quality and liability issues. The use of an advanced marking system to identify and control fraud has been shown to be effective in controlling illegal activity. DeCipher has developed surface enhanced Raman scattering (SERS) spectroscopy as its lead technology for measuring markers in fuel to identify and control malpractice. SERS has many advantages that make it highly suitable for this purpose. The SERS instruments are portable and can be used to monitor fuel at any point in the supply chain. SERS shows high specificity for the marker, with no false positives. Multiple markers can also be detected in a single SERS analysis allowing, for example, specific regional monitoring of fuel. The SERS analysis from fuel is also quick, clear and decisive, with a measurement time of less than 5 minutes. We will present results highlighting our development of the use of a highly stable silver colloid as a SERS substrate to measure the markers at ppb levels. Preliminary results from the use of a solid state SERS substrate to measure fuel markers will also be presented.
Identification of active and quiescent adipose vascular stromal cells.
Lin, Guiting; Xin, Zhongcheng; Zhang, Haiyang; Banie, Lia; Wang, Guifang; Qiu, Xuefeng; Ning, Hongxiu; Lue, Tom F; Lin, Ching-Shwun
2012-02-01
Recent studies have demonstrated the existence of both active and quiescent stem cells in bone marrow, hair follicle and intestine. We attempted to identify active and quiescent vascular stromal cells (VSC) in adipose tissue. For identification of active VSC, adult rats were injected intraperitoneally with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) and their subcutaneous tissue harvested 3 days later. For identification of quiescent VSC, newborn rats were injected intraperitoneally with EdU and their subcutaneous tissue harvested 9 weeks later. The harvested adipose tissues were examined for the co-localization of EdU with VSC marker CD34, smooth muscle marker SMA, endothelial marker RECA and pericyte marker CD140b. In adult rat adipose tissues harvested 3 days after EdU injection, there were 28.80 ± 8.70 (mean ± SD) EdU+ cells/100 × microscopic field, and approximately 6.2% of cell nuclei were labeled with EdU. The percentages of EdU+ cells expressing the following markers were approximately: 84 for CD34, 5.6 for RECA (rat endothelial marker), 3.7 for SMA and 14.8 for CD140b. In the adipose tissues of newborn rats that were harvested 9 weeks after EdU injection, the percentages of EdU+ cells expressing the following markers were approximately: 76 for CD34, 1.8 for RECA, 0 for SMA and 12.9 for CD140b. In both the short-term (active) and long-term (quiescent) EdU-labeled adipose tissues, the EdU label was consistently co-localized with CD34 and in the proximity of CD140b stain or in the adventitia. Both active and quiescent VSC expressed CD34 and localized to capillaries and the adventitia of larger blood vessels.
Molecular markers for colorectal cancer screening
Dickinson, Brandon T.; Kisiel, John; Ahlquist, David A.; Grady, William M.
2016-01-01
Colorectal cancer (CRC), although a significant cause of morbidity and mortality worldwide, has seen a declining incidence and mortality in countries with programmatic screening. Fecal occult blood testing (FOBT) and endoscopic approaches are the predominant screening methods currently. The discovery of the adenoma→carcinoma sequence and a greater understanding of the genetic and epigenetic changes that drive the formation of CRC have contributed to innovative research to identify molecular markers for highly accurate, non-invasive screening tests for CRC. DNA, proteins, messenger RNA, and micro-RNA have all been evaluated. The observation of tumor cell exfoliation into the mucocellular layer of the colonic epithelium and proven stability of DNA in a harsh stool environment make stool DNA a particularly promising marker. The development of a clinically useful stool DNA test has required numerous technical advances, including optimization in DNA stabilization, the development of assays with high analytical sensitivity, and the identification of specific and broadly informative molecular markers. A multi-target stool DNA (MT-sDNA) test, which combines both mutant and methylated DNA markers and a fecal immunochemical test (FIT), recently performed favorably in a large cross-sectional validation study and has been approved by the US Food and Drug Administration (FDA) for the screening of asymptomatic, average risk individuals. The ultimate way in which molecular marker screening assays will be used in clinical practice will require additional studies to determine optimal screening intervals, factors affecting compliance, management of false positive results, and the use of these assays in high-risk populations, as well as other considerations. PMID:25994221