WorldWideScience

Sample records for transferrin diagnostic potential

  1. Decreased CSF transferrin in sCJD: a potential pre-mortem diagnostic test for prion disorders.

    Directory of Open Access Journals (Sweden)

    Ajay Singh

    2011-03-01

    Full Text Available Sporadic Creutzfeldt-Jakob-disease (sCJD is a fatal neurodegenerative condition that escapes detection until autopsy. Recently, brain iron dyshomeostasis accompanied by increased transferrin (Tf was reported in sCJD cases. The consequence of this abnormality on cerebrospinal-fluid (CSF levels of Tf is uncertain. We evaluated the accuracy of CSF Tf, a 'new' biomarker, as a pre-mortem diagnostic test for sCJD when used alone or in combination with the 'current' biomarker total-tau (T-tau. Levels of total-Tf (T-Tf, isoforms of Tf (Tf-1 and Tf-β2, and iron saturation of Tf were quantified in CSF collected 0.3-36 months before death (duration from 99 autopsy confirmed sCJD (CJD+ and 75 confirmed cases of dementia of non-CJD origin (CJD-. Diagnostic accuracy was estimated by non-parametric tests, logistic regression, and receiver operating characteristic (ROC analysis. Area under the ROC curve (AUC, sensitivity, specificity, positive and negative predictive values (PV, and likelihood ratios (LR of each biomarker and biomarker combination were calculated. We report that relative to CJD-, CJD+ cases had lower median CSF T-Tf (125,7093 vs. 217,7893 and higher T-tau (11530 vs. 1266 values. AUC was 0.90 (95% confidence interval (CI, 0.85-0.94 for T-Tf, and 0.93 (95% CI, 0.89-0.97 for T-Tf combined with T-tau. With cut-offs defined to achieve a sensitivity of ∼85%, T-Tf identified CJD+ cases with a specificity of 71.6% (95% CI, 59.1-81.7, positive LR of 3.0 (95% CI, 2.1-4.5, negative LR of 0.2 (95% CI, 0.1-0.3, and accuracy of 80.1%. The effect of patient age and duration was insignificant. T-Tf combined with T-tau identified CJD+ with improved specificity of 87.5% (95%CI, 76.3-94.1, positive LR of 6.8 (95% CI, 3.5-13.1, negative LR of 0.2 (95% CI, 0.1-0.3, positive-PV of 91.0%, negative-PV of 80.0%, and accuracy of 86.2%. Thus, CSF T-Tf, a new biomarker, when combined with the current biomarker T-tau, is a reliable pre-mortem diagnostic test for sCJD.

  2. Primary care requests for anaemia chemistry tests in Spain: potential iron, transferrin and folate over-requesting.

    Science.gov (United States)

    Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Leiva-Salinas, Carlos

    2017-09-01

    To study the regional variability of requests for anaemia chemistry tests in primary care in Spain and the associated economic costs of potential over-requesting. Requests for anaemia tests were examined in a cross-sectional study. Clinical laboratories from different autonomous communities (AACCs) were invited to report on primary care anaemia chemistry tests requested during 2014. Demand for iron, ferritin, vitamin B12 and folate tests per 1000 inhabitants and the ratios of the folate/vitamin B12 and transferrin/ferritin requests were compared between AACCs. We also calculated reagent costs and the number of iron, transferrin and folate tests and the economic saving if every AACC had obtained the results achieved by the AACC with best practice. 110 laboratories participated (59.8% of the Spanish population). More than 12 million tests were requested, resulting in reagent costs exceeding €16.5 million. The serum iron test was the most often requested, and the ferritin test was the most costly (over €7 million). Close to €4.5 million could potentially have been saved if iron, transferrin and folate had been appropriately requested (€6 million when extrapolated to the whole Spanish population). The demand for and expenditure on anaemia chemistry tests in primary care in Spain is high, with significant regional differences between different AACCs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Four variants in transferrin and HFE genes as potential markers of iron deficiency anaemia risk: an association study in menstruating women

    Directory of Open Access Journals (Sweden)

    Arroyo-Pardo Eduardo

    2011-10-01

    Full Text Available Abstract Background Iron deficiency anaemia is a worldwide health problem in which environmental, physiologic and genetic factors play important roles. The associations between iron status biomarkers and single nucleotide polymorphisms (SNPs known to be related to iron metabolism were studied in menstruating women. Methods A group of 270 Caucasian menstruating women, a population group at risk of iron deficiency anaemia, participated in the study. Haematological and biochemical parameters were analysed and 10 selected SNPs were genotyped by minisequencing assay. The associations between genetic and biochemical data were analysed by Bayesian Model Averaging (BMA test and decision trees. Dietary intake of a representative subgroup of these volunteers (n = 141 was assessed, and the relationship between nutrients and iron biomarkers was also determined by linear regression. Results Four variants, two in the transferrin gene (rs3811647, rs1799852 and two in the HFE gene (C282Y, H63D, explain 35% of the genetic variation or heritability of serum transferrin in menstruating women. The minor allele of rs3811647 was associated with higher serum transferrin levels and lower transferrin saturation, while the minor alleles of rs1799852 and the C282Y and H63D mutations of HFE were associated with lower serum transferrin levels. No association between nutrient intake and iron biomarkers was found. Conclusions In contrast to dietary intake, these four SNPs are strongly associated with serum transferrin. Carriers of the minor allele of rs3811647 present a reduction in iron transport to tissues, which might indicate higher iron deficiency anaemia risk, although the simultaneous presence of the minor allele of rs1799852 and HFE mutations appear to have compensatory effects. Therefore, it is suggested that these genetic variants might potentially be used as markers of iron deficiency anaemia risk.

  4. Potential hazards of diagnostic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Houston, C S; Shokeir, M H

    1977-03-01

    There are no precise data for determining the extent of somatic damage from small doses of radiation used in diagnostic radiology. Diagnostic radiation given to pregnant women, knowingly or unknowingly, should rarely reach teratogenic levels causing brain and eye abnormalities. Evidence suggests that it does increase the risk of childhood malignancy, especially leukemia. Although rapidly growing tissues seem most susceptible, all radiation probably carries a very small risk of carcinogenesis. Genetic damage is equally difficult to estimate. Diagnostic radiation of females, even in childhood, may be related to an increased incidence of Down's syndrome in older mothers. Radiation also causes point mutations, which may explain the increase of some genetic abnormalities in progeny of older fathers. Whenever an abdominal or pelvic radiograph is ordered before the end of the reproductive period, there must be a potential benefit to balance the small risk involved.

  5. A Low-Molecular-Weight Ferroxidase Is Increased in the CSF of sCJD Cases: CSF Ferroxidase and Transferrin as Diagnostic Biomarkers for sCJD

    Science.gov (United States)

    Haldar, Swati; Beveridge, ’Alim J.; Wong, Joseph; Singh, Ajay; Galimberti, Daniela; Borroni, Barbara; Zhu, Xiongwei; Blevins, Janis; Greenlee, Justin; Perry, George; Mukhopadhyay, Chinmay K.; Schmotzer, Christine

    2013-01-01

    Abstract Aims: Most biomarkers used for the premortem diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) are surrogate in nature, and provide suboptimal sensitivity and specificity. Results: We report that CJD-associated brain iron dyshomeostasis is reflected in the cerebrospinal fluid (CSF), providing disease-specific diagnostic biomarkers. Analysis of 290 premortem CSF samples from confirmed cases of CJD, Alzheimer's disease, and other dementias (DMs), and 52 non-DM (ND) controls revealed a significant difference in ferroxidase (Frx) activity and transferrin (Tf) levels in sporadic Creutzfeldt-Jakob disease (sCJD) relative to other DM and ND controls. A combination of CSF Frx and Tf discriminated sCJD from other DMs with a sensitivity of 86.8%, specificity of 92.5%, accuracy of 88.9%, and area-under-the receiver-operating-characteristic (ROC) curve of 0.94. This combination provided a similar diagnostic accuracy in discriminating CJD from rapidly progressing cases who died within 6 months of sample collection. Surprisingly, ceruloplasmin and amyloid precursor protein, the major brain Frxs, displayed minimal activity in the CSF. Most of the Frx activity was concentrated in the <3-kDa fraction in normal and diseased CSF, and resisted heat and proteinase-K treatment. Innovation: (i) A combination of CSF Frx and Tf provides disease-specific premortem diagnostic biomarkers for sCJD. (ii) A novel, nonenzymatic, nonprotein Frx predominates in human CSF that is distinct from the currently known CSF Frxs. Conclusion: The underlying cause of iron imbalance is distinct in sCJD relative to other DMs associated with the brain iron imbalance. Thus, change in the CSF levels of iron-management proteins can provide disease-specific biomarkers and insight into the cause of iron imbalance in neurodegenerative conditions. Antioxid. Redox Signal. 19, 1662–1675. PMID:23379482

  6. Potential use of 68Ga-apo-transferrin as a PET imaging agent for detecting Staphylococcus aureus infection

    International Nuclear Information System (INIS)

    Kumar, Vijay; Boddeti, Dilip K.; Evans, Scott G.; Roesch, Frank; Howman-Giles, Robert

    2011-01-01

    Introduction: 67 Ga citrate has been extensively used to detect infection and inflammation since 1971. However, its clinical utility is compromised due to several limitations. The present project explored whether 68 Ga-apo-transferrin ( 68 Ga-TF), when prepared in vitro, is a useful agent for positron emission tomography (PET) imaging of bacterial infection. Methods: An infection was induced in male Wistar rats by injecting 5x10 5 CFU units of Staphyococcus aureus in the right thigh muscle. 68 Ga-TF was synthesized by mixing 68 GaCl 3 with apo-transferrin (TF, 2 mg) in sodium carbonate (0.1 M, pH 7.0) and incubating at 40 o C for 1 h. Animals were injected with 10-15 MBq of 68 Ga-TF containing approximately 0.2 mg TF and imaged at different time intervals using Siemens Biograph PET-CT. Results: When 68 Ga-TF were injected in the infected rats, the infection lesion was detectable within 20 min post injection. The biodistribution showed the uptake at the lesion increased with time as shown by significantly increased standard uptake values for up to 4 h post injection. There was a considerable decrease in the background activity during the same period of study, giving higher target-to-muscle ratios. Blood pool activity at 3 h post injection was insignificant. 68 GaCl 3 (when not conjugated to TF) did not localize at the infection lesion up to 120 min post injection. Conclusion: The preliminary results suggest that 68 Ga-TF is capable of detecting S. aureus infection in the rat model, within an hour after intravenous injection.

  7. Diagnostics of the Enterprise Export Potential

    Directory of Open Access Journals (Sweden)

    Skrynkovskyy Ruslan M.

    2016-11-01

    Full Text Available The aim of the article is to form and develop theoretical and methodological foundations for diagnostics of the enterprise export potential, which should be understood as a process of identification, analysis and assessment of the level of potential possibility and readiness of the enterprise to implement export activities taking into account the impact of interrelated internal variables (goals, technology, structure, tasks, educational and professional potential of the staff and factors of the enterprise external environment (customers, competitors, suppliers, intermediaries, contact audience, etc. in order to ensure a qualitatively new level of its development and formation of its prospects. It is determined that the key business indicators of the system for diagnostics of enterprise export potential are: the level of enterprises competitiveness in the international (global market; the level of competitiveness of enterprise products; the level of competitiveness of enterprise export products; the level of enterprise resource opportunities; the level of enterprise export performance. Prospects for further research in this direction are to develop a classification (specifically detailed list of objectives of the enterprise diagnostics by the level of detail (element, partial, complex, taking into account diagnostics of export potential of the enterprise as part of diagnostic objective.

  8. Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma.

    Science.gov (United States)

    Xie, Yuran; Kim, Na Hyung; Nadithe, Venkatareddy; Schalk, Dana; Thakur, Archana; Kılıç, Ayşe; Lum, Lawrence G; Bassett, David J P; Merkel, Olivia M

    2016-05-10

    Asthma is a worldwide health problem. Activated T cells (ATCs) in the lung, particularly T helper 2 cells (Th2), are strongly associated with inducing airway inflammatory responses and chemoattraction of inflammatory cells in asthma. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence inflammation related genes in ATCs, however, lack of safe and efficient siRNA delivery systems limits the application of siRNA as a therapeutic molecule in asthma. Here, we designed a novel pulmonary delivery system of siRNA, transferrin-polyethylenimine (Tf-PEI), to selectively deliver siRNA to ATCs in the lung. Tf-PEI polyplexes demonstrated optimal physicochemical properties such as size, distribution, zeta-potential, and siRNA condensation efficiency. Moreover, in vitro studies showed significantly enhanced cellular uptake and gene knockdown mediated by Tf-PEI polyplexes in human primary ATCs. Biodistribution of polyplexes in a murine asthmatic model confirmed that Tf-PEI polyplexes can efficiently and selectively deliver siRNA to ATCs. In conclusion, the present work proves the feasibility to target ATCs in asthma via Tf receptor. This strategy could potentially be used to design an efficient siRNA delivery system for asthma therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. A new liquid chromatography-mass spectrometry-based method to quantitate exogenous recombinant transferrin in cerebrospinal fluid: a potential approach for pharmacokinetic studies of transferrin-based therapeutics in the central nervous systems.

    Science.gov (United States)

    Wang, Shunhai; Bobst, Cedric E; Kaltashov, Igor A

    2015-01-01

    Transferrin (Tf) is an 80 kDa iron-binding protein that is viewed as a promising drug carrier to target the central nervous system as a result of its ability to penetrate the blood-brain barrier. Among the many challenges during the development of Tf-based therapeutics, the sensitive and accurate quantitation of the administered Tf in cerebrospinal fluid (CSF) remains particularly difficult because of the presence of abundant endogenous Tf. Herein, we describe the development of a new liquid chromatography-mass spectrometry-based method for the sensitive and accurate quantitation of exogenous recombinant human Tf in rat CSF. By taking advantage of a His-tag present in recombinant Tf and applying Ni affinity purification, the exogenous human serum Tf can be greatly enriched from rat CSF, despite the presence of the abundant endogenous protein. Additionally, we applied a newly developed (18)O-labeling technique that can generate internal standards at the protein level, which greatly improved the accuracy and robustness of quantitation. The developed method was investigated for linearity, accuracy, precision, and lower limit of quantitation, all of which met the commonly accepted criteria for bioanalytical method validation.

  10. Use of Spectroscopic, Zeta Potential and Molecular Dynamic Techniques to Study the Interaction between Human Holo-Transferrin and Two Antagonist Drugs: Comparison of Binary and Ternary Systems

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Saberi

    2012-03-01

    Full Text Available For the first time, the binding of ropinirole hydrochloride (ROP and aspirin (ASA to human holo-transferrin (hTf has been investigated by spectroscopic approaches (fluorescence quenching, synchronous fluorescence, time-resolved fluorescence, three-dimensional fluorescence, UV-vis absorption, circular dichroism, resonance light scattering, as well as zeta potential and molecular modeling techniques, under simulated physiological conditions. Fluorescence analysis was used to estimate the effect of the ROP and ASA drugs on the fluorescence of hTf as well as to define the binding and quenching properties of binary and ternary complexes. The synchronized fluorescence and three-dimensional fluorescence spectra demonstrated some micro-environmental and conformational changes around the Trp and Tyr residues with a faint red shift. Thermodynamic analysis displayed the van der Waals forces and hydrogen bonds interactions are the major acting forces in stabilizing the complexes. Steady-state and time-resolved fluorescence data revealed that the fluorescence quenching of complexes are static mechanism. The effect of the drugs aggregating on the hTf resulted in an enhancement of the resonance light scattering (RLS intensity. The average binding distance between were computed according to the forster non-radiation energy transfer theory. The circular dichroism (CD spectral examinations indicated that the binding of the drugs induced a conformational change of hTf. Measurements of the zeta potential indicated that the combination of electrostatic and hydrophobic interactions between ROP, ASA and hTf formed micelle-like clusters. The molecular modeling confirmed the experimental results. This study is expected to provide important insight into the interaction of hTf with ROP and ASA to use in various toxicological and therapeutic processes.

  11. Multiple sclerosis - etiology and diagnostic potential.

    Science.gov (United States)

    Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

    2017-06-30

    Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

  12. Multiple sclerosis - etiology and diagnostic potential

    Directory of Open Access Journals (Sweden)

    Joanna Kamińska

    2017-06-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS, secondary progressive multiple sclerosis (SPSM, primary progressive multiple sclerosis (PPMS, and progressive-relapsing multiple sclerosis (RPMS. Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald’s diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI, cerebrospinal fluid (CSF analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of differentdiagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

  13. Brain natriuretic peptide: Diagnostic potential in dogs

    Directory of Open Access Journals (Sweden)

    Spasojević-Kosić Ljubica

    2009-01-01

    Full Text Available The endocrine role of the heart is evident in the secretion of noradrenaline and natriuretic peptides. The secretion of natriuretic peptides presents a useful mechanism for different conditions of cardiac dysfunction. Brain natriuretic peptide (BNP has been accepted in human cardiology as a biomarker for cardiac insufficiency and coronary arterial disease. The specificity of the BNP structure is specie-specific, so that the testing of diagnostic and prognostic potential in dogs requires the existence of a test that is a homologue for that animal specie. The existence of an adequate method for measuring BNP concentration makes possible its implementation as a screening test in everyday clinical practice. .

  14. SDQ: Discriminative validity and diagnostic potential

    Directory of Open Access Journals (Sweden)

    Thaysa Brinck Fernandes Silva

    2015-06-01

    Full Text Available The Strengths and Difficulties Questionnaire (SDQ was designed to screen for behavioral problems in youths based on cutoff points that favor the instrument’s diagnostic sensitivity. The present study aimed to analyze the discriminative validity of the SDQ to identify behavioral difficulties and prosocial resources in school-age children compared with the diagnostic data collected by the corresponding sections of the Development and Well-being Assessment (DAWBA. In addition, new cutoff points that value specificity were defined for the SDQ scales, exploring its diagnostic potential. This study was conducted in Brazil and assessed a community convenience sample that consisted of 120 children aged 6 to 12 years who were not under psychological/psychiatric treatment. The mothers of the participants also completed a sociodemographic questionnaire. Descriptive statistics were used to clinically characterize the sample. A ROC curve was used to assess the discriminant validity of the SDQ, and new cutoff points were established to maximize the instrument’s specificity. The new cutoff points enabled a significant increase in specificity without a significant loss of sensitivity, which favors approaches based on measures of screening and diagnosis yet does not damage the instrument’s screening capacity. The following increases were observed: 100% for the depressive disorder scale (cutoff point=7, 95.1% for the generalized anxiety disorder scale (cutoff point=7, 46.6% for the conduct disorder scale (cutoff point=6, 19.2% for the hyperactive disorder scale (cutoff point=8, and 27.6% for the antisocial personality disorder scale (cutoff point=6. A cutoff point of 8 was applied to the prosocial behavior scale, which exhibited a 62.1% increase in specificity. The use of more specific cutoff points generated more accurate results and favored SDQ's use, particularly in contexts of care that require more precise and faster procedures for identification of

  15. Iron, transferrin and myelinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sergeant, C. E-mail: sergeant@cenbg.in2p3.fr; Vesvres, M.H.; Deves, G.; Baron, B.; Guillou, F

    2003-09-01

    Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5{sup '} and 3{sup '} untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport.

  16. Iron, transferrin and myelinogenesis

    International Nuclear Information System (INIS)

    Sergeant, C.; Vesvres, M.H.; Deves, G.; Baron, B.; Guillou, F.

    2003-01-01

    Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5 ' and 3 ' untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport

  17. Annotating MYC status with 89Zr-transferrin imaging.

    Science.gov (United States)

    Holland, Jason P; Evans, Michael J; Rice, Samuel L; Wongvipat, John; Sawyers, Charles L; Lewis, Jason S

    2012-10-01

    A noninvasive technology that quantitatively measures the activity of oncogenic signaling pathways could have a broad impact on cancer diagnosis and treatment with targeted therapies. Here we describe the development of (89)Zr-desferrioxamine-labeled transferrin ((89)Zr-transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of (89)Zr-transferrin produces high-contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, (89)Zr-transferrin imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as in prostatic intraepithelial neoplasia (PIN) before histological or anatomic evidence of invasive cancer. These preclinical data establish (89)Zr-transferrin as a sensitive tool for noninvasive measurement of oncogene-driven TFRC expression in prostate and potentially other cancers, with prospective near-term clinical application.

  18. Acute toxicity profile of cadmium revealed by proteomics in brain tissue of Paralichthys olivaceus: Potential role of transferrin in cadmium toxicity

    International Nuclear Information System (INIS)

    Zhu Jinyong; Huang Heqing; Bao Xiaodong; Lin Qingmei; Cai Zongwei

    2006-01-01

    An analytical approach using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) separated proteins from the brain tissue of the fish Paralichthys olivaceus. Approximately 600 protein spots were detected from the brain sample when applying 600 μg protein to a 2D-PAGE gel in the pH range 3.5-10.0. Compared to a control sample, significant changes of 24 protein spots were observed in the fish tissue exposed to acute toxicity of seawater cadmium (SCAT) at 10 ppm for 24 h. Among these spots, nine were down-regulated, nine were up-regulated, two showed high expression, and four showed low expression. The collected spots were identified by peptide mass fingerprinting (PMF) and database search, and they were further classified by LOCtree, a hierarchical system of support vector machines which predict their sub-cellular localization. The amount of transferrin expression in brain cells decreased linearly with the increase of SCAT concentration in seawater. Among the 24 proteins identified on a 2D-PAGE gel, 9 demonstrated a synchronous response to acute cadmium, suggesting that they might represent a biomarker profile. Based on their variable levels and trends on the 2D-PAGE gel this protein (likely to be transferrin) suggesting they might be utilized as biomarkers to investigate cadmium pollution levels in seawater and halobios survival, as well as to evaluate the degree of risk of human fatalities. The results indicate that the application of multiple biomarkers has an advantage over a single biomarker for monitoring levels of environmental contamination

  19. Serum transferrin receptor in polycythemia.

    Science.gov (United States)

    Manteiga, R; Remacha, A F; Sardà, M P; Ubeda, J

    1998-10-01

    We measured serum transferrin receptor (sTfR) levels in 22 patients with polycythemia vera and in 26 cases of secondary polycythemia. In our study, raised sTfR levels in both polycythemia groups were related to iron deficiency.

  20. Synthesis and characterization of human transferrin-stabilized gold nanoclusters

    International Nuclear Information System (INIS)

    Le Guevel, Xavier; Schneider, Marc; Daum, Nicole

    2011-01-01

    Human transferrin has been biolabelled with gold nanoclusters (Au NCs) using a simple, fast and non-toxic method. These nanocrystals ( em = 695 nm). Structural investigation and photophysical measurements show a high population of clusters formed of 22-33 gold atoms covalently bound to the transferrin. In solutions with pH ranging from 5 to 10 and in buffer solutions (PBS, HEPES), those biolabelled proteins exhibit a good stability. No significant quenching effect of the fluorescent transferrin has been detected after iron loading of iron-free transferrin (apoTf) and in the presence of a specific polyclonal antibody. Additionally, antibody-induced agglomeration demonstrates no alteration in the protein activity and the receptor target ability. MTT and Vialight Plus tests show no cytotoxicity of these labelled proteins in cells (1 μg ml -1 -1 mg ml -1 ). Cell line experiments (A549) indicate also an uptake of the iron loaded fluorescent proteins inside cells. These remarkable data highlight the potential of a new type of non-toxic fluorescent transferrin for imaging and targeting.

  1. The structural basis of transferrin sequestration by transferrin-binding protein B

    Energy Technology Data Exchange (ETDEWEB)

    Calmettes, Charles; Alcantara, Joenel; Yu, Rong-Hua; Schryvers, Anthony B.; Moraes, Trevor F. (Toronto); (Calgary)

    2012-03-28

    Neisseria meningitidis, the causative agent of bacterial meningitis, acquires the essential element iron from the host glycoprotein transferrin during infection through a surface transferrin receptor system composed of proteins TbpA and TbpB. Here we present the crystal structures of TbpB from N. meningitidis in its apo form and in complex with human transferrin. The structure reveals how TbpB sequesters and initiates iron release from human transferrin.

  2. Plasma diagnostics with a retarding potential analyzer

    International Nuclear Information System (INIS)

    Jack, T.M.

    1996-01-01

    The plasma rocket is located at NASA Johnson Space Center. To produce a thrust in space, an inert gas is ionized into a plasma and heated in the linear section of a tokamak fusion device. The magnetic field used to contain the plasma has a magnitude of 2--10 kGauss. The plasma plume has a variable thrust and specific impulse. A high temperature retarding potential analyzer (RPA) is being developed to characterize the plasma in the plume and at the edge of the magnetically contained plasma. The RPA measures the energy and density of ions or electrons entering into its solid angle of collection. An oscilloscope displays the ion flux versus the collected current. All measurements are made relative to the facility ground. Testing of this device involves the determination of its output parameters, sensitivity, and responses to a wide range of energies and densities. Each grid will be tested individually by changing only its voltage and observing the output from the RPA. To verify that the RPA is providing proper output, it is compared to the output from a Langmuir or Faraday probe

  3. Transferrin metabolism in alcoholic liver disease

    International Nuclear Information System (INIS)

    Potter, B.J.; Chapman, R.W.; Nunes, R.M.; Sorrentino, D.; Sherlock, S.

    1985-01-01

    The metabolism of transferrin was studied using purified 125 I-labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group. There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 +/- 0.3 gm per liter vs. 2.9 +/- 0.2; p less than 0.01), resulting from diminished total body synthesis (0.9 +/- 0.2 mg per kg per hr vs. 1.8 +/- 0.2; p less than 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 +/- 0.3 mg per kg per hr) was significantly increased when compared with controls (p less than 0.05). For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = +0.70; p less than 0.01) but the serum iron did not. These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerated

  4. Transferrin-facilitated lipofection gene delivery strategy: characterization of the transfection complexes and intracellular trafficking.

    Science.gov (United States)

    Joshee, Nirmal; Bastola, Dhundy R; Cheng, Pi-Wan

    2002-11-01

    We previously showed that mixing transferrin with a cationic liposome prior to the addition of DNA, greatly enhanced the lipofection efficiency. Here, we report characterization of the transfection complexes in formulations prepared with transferrin, lipofectin, and DNA (pCMVlacZ) in various formulations. DNA in all the formulations that contain lipofectin was resistant to DNase I treatment. Transfection experiments performed in Panc 1 cells showed that the standard formulation, which was prepared by adding DNA to a mixture of transferrin and lipofectin, yielded highest transfection efficiency. There was no apparent difference in zeta potential among these formulations, but the most efficient formulation contained complexes with a mean diameter of three to four times that of liposome and the complexes in other gene delivery formulations. Transmission electron microscopic examination of the standard transfection complexes formulated using gold-labeled transferrin showed extended circular DNA decorated with transferrin as compared to extensively condensed DNA found in lipofectin-DNA complexes and heterogeneous structures in other formulations. By confocal microscopy, DNA and transferrin were found to colocalize at the perinuclear space and in the nucleus, suggesting cotransportation intracellularly, including nuclear transport. We propose that transferrin enhances the transfection efficiency of the standard lipofection formulation by preventing DNA condensation, and facilitating endocytosis and nuclear targeting.

  5. A facile drug delivery system preparation through the interaction between drug and iron ion of transferrin

    International Nuclear Information System (INIS)

    Zhou, Lin; Liu, Jihua; Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong; Yu, Boyang; Shen, Jian

    2013-01-01

    Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A–transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A–transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin

  6. A facile drug delivery system preparation through the interaction between drug and iron ion of transferrin

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Lin [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China); Liu, Jihua [China Pharmaceutical University, Department of Complex Prescription of TCM (China); Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong, E-mail: zhoujiahong@njnu.edu.cn [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China); Yu, Boyang, E-mail: boyangyu59@163.com [China Pharmaceutical University, Department of Complex Prescription of TCM (China); Shen, Jian [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China)

    2013-09-15

    Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A-transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A-transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin.

  7. Assessment of the Diagnostic Potential of Clinotech TB Screen Test ...

    African Journals Online (AJOL)

    The Clinotech TB Screen test, a 3rd generation multi-antigen rapid chromatographic immunoassay for detection of IgG antibodies in serum against recombinant protein antigens 38kDa, 16kDa and 6kDa, was assessed for its diagnostic potential for diagnosis of active pulmonary TB in routine TB control programme in Abia ...

  8. Gene transcripts as potential diagnostic markers for allergic contact dermatitis

    DEFF Research Database (Denmark)

    Hansen, Malene Barré; Skov, Lone; Menné, Torkil

    2005-01-01

    The standard procedure for diagnosing allergic contact dermatitis is to perform a patch test. Because this has several disadvantages, the development of a new in vitro test system would be of immense value. Gene transcripts that distinguish allergics from non-allergics may have the potential...... widely available. The 26 differentially expressed genes identified in this study may potentially function as diagnostic markers for contact sensitivity....

  9. Kinetics of Transferrin and Transferrin-Receptor during Iron Transport through Blood Brain Barrier

    Science.gov (United States)

    Khan, Aminul; Liu, Jin; Dutta, Prashanta

    2017-11-01

    Transferrin and its receptors play an important role during the uptake and transcytosis of iron by blood brain barrier (BBB) endothelial cells to maintain iron homeostasis in BBB endothelium and brain. In the blood side of BBB, ferric iron binds with the apo-transferrin to form holo-transferrin which enters the endothelial cell via transferrin receptor mediated endocytosis. Depending on the initial concentration of iron inside the cell endocytosed holo-transferrin can either be acidified in the endosome or exocytosed through the basolateral membrane. Acidification of holo-transferrin in the endosome releases ferrous irons which may either be stored and used by the cell or transported into brain side. Exocytosis of the holo-transferrin through basolateral membrane leads to transport of iron bound to transferrin into brain side. In this work, kinetics of internalization, recycling and exocytosis of transferrin and its receptors are modeled by laws of mass action during iron transport in BBB endothelial cell. Kinetic parameters for the model are determined by least square analysis. Our results suggest that the cell's initial iron content determines the extent of the two possible iron transport pathways, which will be presented in this talk Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

  10. Adaptation of transferrin protein and glycan synthesis

    NARCIS (Netherlands)

    G. de Jong (Gerard); W.L. van Noort (W.); R.A. Feelders (Richard); C.M.H. de Jeu-Jaspars (Nel); H.G. van Eijk (Henk)

    1992-01-01

    textabstractWe report the patterns of variability in transferrin structure in pregnancy, iron deficiency anemia, women using oral contraceptives, nonanaemic rheumatoid arthritis, iron deficient rheumatoid arthritis and anemia of the chronic diseases. Changes in microheterogeneity were assessed by

  11. Hemin inhibits internalization of transferrin by reticulocytes and promotes phosphorylation of the membrane transferrin receptor

    International Nuclear Information System (INIS)

    Cox, T.M.; O'Donnell, M.W.; Aisen, P.; London, I.M.

    1985-01-01

    Addition of hemin to reticulocytes inhibits incorporation of iron from transferrin. Heme also regulates protein synthesis in immature erythroid cells through its effects on phosphorylation of the initiation factor eIF-2. The authors have examined its effects on endocytosis of iron-transferrin and phosphorylation of the transferrin receptor. Hemin reduced iron transport but increased cell-associated transferrin. During uptake of 125 I-labeled transferrin in the steady state, the use of a washing technique to dissociate bound transferrin on the cell membrane showed that radioligand accumulated on the surface of hemin-treated cells. Receptor phosphorylation was investigated by immunoprecipitation of reticulocyte extracts after metabolic labeling with [ 32 P]P/sub i/. In the absence of ligand, phosphorylated receptor was chiefly localized on cell stroma. Exposure to transferrin increased cytosolic phosphorylated receptor from 15-30% to approximately 50% of the total, an effect overcome by hemin treatment. The findings suggest a possible relationship of phosphorylation to endocytosis of the transferrin receptor in reticulocytes

  12. Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Brian J. Peter

    2008-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer deaths worldwide. Effective treatment of HCC patients is hampered by the lack of sensitive and specific diagnostic markers of HCC. Alpha-fetoprotein (AFP, the currently used HCC marker, misses 30%–50% of HCC patients, who therefore remain undiagnosed and untreated. In order to identify novel diagnostic markers that can be used individually or in combination with AFP, we used an antibody array platform to detect the levels of candidate proteins in the plasma of HCC patients (n = 48 and patients with chronic hepatitis B or C viral infections (n = 19 (both of which are the major risk factors of HCC. We identified 7 proteins that significantly differentiate HCC patients from hepatitis patients (p < 0.05 (AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1.Importantly, we also identified 8 proteins that significantly differentiate HCC patients with ‘normal’ levels of AFP (<20 ng/ml from hepatitis patients (p < 0.05 (IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, and SELL. These markers are potentially important complementary markers to AFP. Using an independent immunoassay method in an independent group of 23 HCC patients and 22 hepatitis patients, we validated that plasma levels of CTNNB were significantly higher in the HCC group (p = 0.020. In conclusion, we used an antibody array platform to identify potential circulating diagnostic markers of HCC, some of which may be valuable when used in combination with AFP. The clinical utility of these newly identified HCC diagnostic markers needs to be systematically evaluated.

  13. Specificity of chicken and mammalian transferrins in myogenesis

    International Nuclear Information System (INIS)

    Beach, R.L.; Popiela, Heinz; Festoff, B.W.

    1985-01-01

    Chicken transferrins isolated from eggs, embryo extract, serum or ischiatic-peroneal nerves are able to stimulate incorporation of ( 3 H)thymidine, and promote myogenesis by primary chicken muscles cells in vitro. Mammalian transferrins (bovine, rat, mouse, horse, rabbit, and human) do not promote ( 3 H)thymidine incorporation or myotube development. Comparison of the peptide fragments obtained after chemical or limited proteolytic cleavage demonstrates that the four chicken transferrins are all indistinguishable, but they differ considerably from the mammalian transferrins. The structural differences between chicken and mammalian transferrins probably account for the inability of mammalian transferrins to act as mitogens for, and to support myogenesis of, primary chicken muscle cells. (author)

  14. Issues in contemporary and potential future molecular diagnostics for dengue.

    Science.gov (United States)

    Sekaran, Shamala Devi; Soe, Hui Jen

    2017-03-01

    Dengue has been the most common arbovirus infection worldwide with 2.5 billion people living in over 100 endemic tropical and subtropical regions. Due to the high number of asymptomatic cases and the signs and symptoms being rather unspecific, dengue cases are often under-reported and might influence dengue surveillance programs. Therefore, a rapid, easy to use, inexpensive, and highly sensitive and specific diagnostic tool is essential for early and accurate diagnosis to ease the clinical management of patients as well as for the development of new interventions. Areas covered: This report discusses the contemporary dengue diagnostic tool, mainly from the aspect of molecular diagnosis where an overview of several nuclei acid amplification tests has been included. Potential molecular diagnostic tools such as biosensor and microarray are also discussed in this report. Expert commentary: Rapidness and accuracy in terms of sensitivity and specificity is imperative in dengue diagnosis for both clinical management and surveillance of dengue to ensure early treatment and corrective control measures can be carried out. In the next five years it is expected that there will be newer tests developed using not only the lateral flow techniques but more specifically biosensors and nanotechnology. These new technologies will have to be validated with the appropriate number and category of samples and to address the issue of cross-reactivity.

  15. Identification of mimotopes of Mycobacterium leprae as potential diagnostic reagents

    Directory of Open Access Journals (Sweden)

    Alban Silvana M

    2013-01-01

    Full Text Available Abstract Background An early diagnostic test for detecting infection in leprosy is fundamental for reducing patients’ sequelae. The currently used lepromin is not adequate for disease diagnosis and, so far, no antigen to be used in intradermoreaction has proved to be sensitive and specific for that purpose. Aiming at identifying new reagents to be used in skin tests, candidate antigens were investigated. Methods Random peptide phage display libraries were screened by using antibodies from leprosy patients in order to identify peptides as diagnostic reagents. Results Seven different phage clones were identified using purified antibodies pooled from sera of leprosy patients. When the clones were tested with serum samples by ELISA, three of them, 5A, 6A and 1B, allowed detecting a larger number of leprosy patients when compared to controls. The corresponding peptides expressed by selected phage clones were chemically synthesized. A pilot study was undertaken to assess the use of peptides in skin tests. The intradermal challenge with peptides in animals previously sensitized with Mycobacterium leprae induced a delayed-type hypersensitivity with peptide 5A (2/5 and peptide 1B (1/5. In positive controls, there was a 3/5 reactivity for lepromin and a 4/5 reactivity of the sensitized animals with soluble extract of M. leprae. Conclusions The preliminary data suggest that may be possible to develop reagents with diagnostic potential based on peptide mimotopes selected by phage display using polyclonal human antibodies.

  16. Phorbol diesters and transferrin modulate lymphoblastoid cell transferrin receptor expression by two different mechanisms

    International Nuclear Information System (INIS)

    Alcantara, O.; Phillips, J.L.; Boldt, D.H.

    1986-01-01

    Expression of transferrin receptors (TfR) by activated lymphocytes is necessary for lymphocyte DNA synthesis and proliferation. Regulation of TfR expression, therefore, is a mechanism by which the lymphocyte's proliferative potential may be directed and controlled. The authors studied mechanisms by which lymphoblastoid cells modulate TfR expression during treatment with phorbol diesters or iron transferrin (FeTf), agents which cause downregulation of cell surface TfR. Phorbol diester-induced TfR downregulation occurred rapidly, being detectable at 2 min and reaching maximal decreases of 50% by 15 min. It was inhibited by cold but not by agents that destabilize cytoskeletal elements. Furthermore, this downregulation was reversed rapidly by washing or by treatment with the membrane interactive agent, chlorpromazine. In contrast, FeTf-induced TfR downregulation occurred slowly. Decreased expression of TfR was detectable only after 15 min and maximal downregulation was achieved after 60 min. Although FeTf-induced downregulation also was inhibited by cold, it was inhibited in addition by a group of microtubule destabilizing agents (colchicine, vinblastine, podophyllotoxin) or cytochalasin B, a microfilament inhibitor. Furthermore, FeTf-induced downregulation was not reversed readily by washing or by treatment with chlorpromazine. Phorbol diesters cause TfR downregulation by a cytoskeleton-independent mechanism. These data indicate that TfR expression is regulated by two independent mechanisms in lymphoblastoid cells, and they provide the possibility that downregulation of TfR by different mechanisms may result in different effects in these cells

  17. Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias

    International Nuclear Information System (INIS)

    Muta, K.; Nishimura, J.; Ideguchi, H.; Umemura, T.; Ibayashi, H.

    1987-01-01

    To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: number of binding sites; affinity; and recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of 125 I-transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects. Among those with an aplastic anemia, hemolytic anemia, myelodysplastic syndrome, and polycythemia vera compared to normal subjects, there were no considerable differences in the numbers of binding sites. The dissociation constants (Kd) were measured using Scatchard analysis. The apparent Kd was unchanged (about 10 nmol/L) in patients and normal subjects. The kinetics of endocytosis and exocytosis of 125 I-transferrin, examined by acid treatment, revealed no variations in recycling kinetics among the patients and normal subjects. These data suggest that iron uptake is regulated by modulation of the number of surface transferrin receptors, thereby reflecting the iron demand of the erythroblast

  18. The characteristics of transferrin variants by carbohydrate-deficient transferrin tests using capillary zone electrophoresis.

    Science.gov (United States)

    Yoo, Gilsung; Kim, Juwon; Yoon, Kap Joon; Lee, Jong-Han

    2018-04-17

    Transferrin is the major plasma transport protein for iron. We aimed to investigate the characteristics of transferrin variant by carbohydrate-deficient transferrin (CDT) test using capillary zone electrophoresis. We retrospectively analyzed the CDT tests of 2449 patients from March 2009 to May 2017 at a tertiary hospital in Korea. CDT was quantified using a Capillarys 2 system (Sebia, Lisses, France) by capillary zone electrophoresis. The characteristics of variant transferrin patterns using electropherogram of CDT tests were analyzed. Seventy-seven (3.1%) patients were classified as variant transferrin. Mean age of these patients was 51.8 years, and the male-to-female ratio was 3.5:1. The most common variants were the BC variants (n = 37), followed by the CD variants (n = 27), unclear patterns (n = 7), BD variants (n = 3), CC variants (n = 2), misclassification (n = 1). In the variant Tf group, the most common disease was alcoholic liver cirrhosis (n = 22, 28.6%), followed by the toxic effects of substances (n = 17, 22.1%), and mental and behavioral disorders attributable to alcohol (n = 11, 14.3%). Nonvariant group showed a predominance of the toxic substance effects (n = 880, 37.1%), a personal history of suicide attempts (n = 634, 26.7%), and mental and behavioral disorders due to alcohol (n = 336, 14.2%). We analyzed the basic characteristics of variant transferrin by CDT tests using capillary zone electrophoresis. The prevalence of variant transferrin was 3.1% of the study subjects. Male patients, alcohol abusers, and liver cirrhosis patients predominated in the variant transferrin population. Further prospective studies are warranted to elucidate variant transferrin in clinical practice. © 2018 Wiley Periodicals, Inc.

  19. 21 CFR 864.9600 - Potentiating media for in vitro diagnostic use.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Potentiating media for in vitro diagnostic use... Manufacture Blood and Blood Products § 864.9600 Potentiating media for in vitro diagnostic use. (a) Identification. Potentiating media for in vitro diagnostic use are media, such as bovine albumin, that are used...

  20. The Physics and Diagnostic Potential of Ultraviolet Spectropolarimetry

    Science.gov (United States)

    Trujillo Bueno, Javier; Landi Degl'Innocenti, Egidio; Belluzzi, Luca

    2017-09-01

    The empirical investigation of the magnetic field in the outer solar atmosphere is a very important challenge in astrophysics. To this end, we need to identify, measure and interpret observable quantities sensitive to the magnetism of the upper chromosphere, transition region and corona. This paper provides an overview of the physics and diagnostic potential of spectropolarimetry in permitted spectral lines of the ultraviolet solar spectrum, such as the Mg ii h and k lines around 2800 Å, the hydrogen Lyman-α line at 1216 Å, and the Lyman-α line of He ii at 304 Å. The outer solar atmosphere is an optically pumped vapor and the linear polarization of such spectral lines is dominated by the atomic level polarization produced by the absorption and scattering of anisotropic radiation. Its modification by the action of the Hanle and Zeeman effects in the inhomogeneous and dynamic solar atmosphere needs to be carefully understood because it encodes the magnetic field information. The circular polarization induced by the Zeeman effect in some ultraviolet lines (e.g., Mg ii h & k) is also of diagnostic interest, especially for probing the outer solar atmosphere in plages and more active regions. The few (pioneering) observational attempts carried out so far to measure the ultraviolet spectral line polarization produced by optically pumped atoms in the upper chromosphere, transition region and corona are also discussed. We emphasize that ultraviolet spectropolarimetry is a key gateway to the outer atmosphere of the Sun and of other stars.

  1. Pregnancy and variations of carbohydrate-deficient transferrin levels measured by the candidate reference HPLC method.

    Science.gov (United States)

    Bianchi, Vincenza; Ivaldi, Alessandra; Raspagni, Alessia; Arfini, Carlo; Vidali, Matteo

    2011-01-01

    Contrasting data are available on the diagnostic accuracy of carbohydrate-deficient transferrin (CDT) during pregnancy. These differences may depend in part on how CDT was evaluated and expressed. Here, we report on variations of CDT levels in pregnant women using the high performance liquid chromatography (HPLC) candidate reference method. Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, mean corpuscular volume, serum transferrin, urine and serum ethyl glucuronide and CDT were measured in 64 women, self-reporting as non-alcohol abusers (age: median 34, IQR: 28-38), at different stages of normal pregnancy (gestational weeks: median 28, IQR: 8-33). CDT was expressed as percentage of disialotransferrin to total transferrin (%CDT). Transferrin was associated with both %CDT (r = 0.66; P pregnancy trimester (first trimester: mean 1.01% (SD 0.19); second trimester: 1.30% (SD 0.14); third trimester: 1.53% (SD 0.22); ANOVA P pregnancy trimesters (P pregnancy and CDT could be more complex. The diagnostic accuracy of CDT for detecting alcohol abuse in a legal context may be limited in pregnant women and the effect of gestational age should be considered.

  2. Potential market for novel tuberculosis diagnostics: worth the investment?

    Science.gov (United States)

    Kik, Sandra V; Denkinger, Claudia M; Jefferson, Carole; Ginnard, Janet; Pai, Madhukar

    2015-04-01

    The potential available market (PAM) for new diagnostics for tuberculosis that meet the specifications of the high-priority target product profiles (TPPs) is currently unknown. We estimated the PAM in 2020 in 4 high-burden countries (South Africa, Brazil, China, and India) for tests that meet the specifications outlined in the TPPs. The yearly PAM was estimated for the most likely application of each TPP. In 2020 the PAM for all 4 countries together was estimated to be (1) 12M tests/year with a value of 48M-71M USD for a sputum smear-replacement test; (2) 16M tests/year with a value of 65M-97M USD for a biomarker test; (3) 18M tests/year with a value of 18M-35M USD for a triage test; (4) 12M tests/year with a value of 59M-2238M USD for a tuberculosis detection plus drug susceptibility test (DST) all-in-one or 1.5M tests/year for a DST that follows a positive tuberculosis detection test with a corresponding value of 75M-121M for both tuberculosis detection and DST. Although there is a considerable potential market for novel tuberculosis diagnostics that fit the specification of the TPPs in the 4 high-burden countries, the actual market for an individual product remains uncertain. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

    NARCIS (Netherlands)

    de Swart, Louise; Hendriks, Jan C. M.; van der Vorm, Lisa N.; Cabantchik, Z. Ioav; Evans, Patricia J.; Hod, Eldad A.; Brittenham, Gary M.; Furman, Yael; Wojczyk, Boguslaw; Janssen, Mirian C. H.; Porter, John B.; Mattijssen, Vera E. J. M.; Biemond, Bart J.; MacKenzie, Marius A.; Origa, Raffaella; Galanello, Renzo; Hider, Robert C.; Swinkels, Dorine W.

    2016-01-01

    Non-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrin-bound iron and 4 for labile plasma iron)

  4. Early diagnostic potential of APC hypermethylation in esophageal cancer

    Directory of Open Access Journals (Sweden)

    Wang B

    2018-02-01

    Full Text Available Bujiang Wang,1 Haojun Song,1 Haizhong Jiang,1 Yangbo Fu,1 Xiaoyun Ding,1 Chongchang Zhou2 1Department of Gastroenterology, Laboratory of Digestive Diseases, Ningbo First Hospital, Ningbo, 2Department of Otorhinolaryngology Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China Background: The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC. However, the association between APC methylation and the initiation and progression of EC is poorly understood. Purpose and methods: The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett’s esophagus (BE, and 782 controls. Results: Our results showed higher methylation of APC in EC (OR = 23.33, P < 0.001 and BE (OR = 9.34, P < 0.001 than in normal controls. Whereas APC methylation in EC was similar to that in BE (P = 0.052, it was not associated with tumor stage (P = 0.204. Additionally, APC methylation was not significantly associated with overall survival (OS and relapse-free survival (RFS in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Conclusion: Our results imply that APC methylation detection is a potential diagnostic biomarker for EC and BE. Keywords: esophageal cancer, Barrett’s esophagus, methylation, APC

  5. Clinical diagnostic potentials of thyroid ultrasonography and scintigraphy; An evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Torizuka, Tatsuo; Kasagi, Kanji; Hatabu, Hiroto; Misaki, Takashi; Iida, Yasuhiro; Konishi, Junji (Kyoto Univ. (Japan). Hospital); Endo, Keigo

    1993-06-01

    This prospective study was designed to evaluate the potential contributions of high resolution ultrasonography (US) and Tc-99m scintigraphy in the routine diagnosis of thyroid disease. The diagnostic impacts of US and Tc-99m scintigraphy results in 177 patients visiting our thyroid clinic were assessed and scored according to the following criteria: when the information provided by either test supported, confirmed or changed the initial clinical diagnosis, they received scores of 2, 3 and 4 respectively, while score 1 was given when the test itself was useless for the differential diagnosis. US identified focal lesions that both palpation and scintigraphy had failed to detect in 14 (12.1%) of 116 patients with diffuse thyroid diseases, suggesting the necessity of Hashimoto's thyroiditis, adenoma, adenocarcinoma and adenomatous goiter, and vice versa in the diagnosis of hyperthyroid and euthyroid Graves's diseases. Thus, the advantages of US over scintigraphy for morphological evaluation were confirmed. US was particularly useful for the differential diagnosis of adenomatous goiter from Hashimoto's thyroiditis or a single nodular disease. In contrast, scintigraphy gave functional images, being especially helpful for the differential diagnosis of thyrotoxicosis. (author).

  6. Early diagnostic potential of APC hypermethylation in esophageal cancer.

    Science.gov (United States)

    Wang, Bujiang; Song, Haojun; Jiang, Haizhong; Fu, Yangbo; Ding, Xiaoyun; Zhou, Chongchang

    2018-01-01

    The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC). However, the association between APC methylation and the initiation and progression of EC is poorly understood. The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett's esophagus (BE), and 782 controls. Our results showed higher methylation of APC in EC (OR = 23.33, P APC methylation in EC was similar to that in BE ( P = 0.052), it was not associated with tumor stage ( P = 0.204). Additionally, APC methylation was not significantly associated with overall survival (OS) and relapse-free survival (RFS) in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Our results imply that APC methylation detection is a potential diagnostic biomarker for EC and BE.

  7. Review of Mycobacteriumavium subsp. paratuberculosis antigen candidates with diagnostic potential

    DEFF Research Database (Denmark)

    Mikkelsen, Heidi; Aagaard, Claus; Nielsen, Søren Saxmose

    2011-01-01

    antigens, heat shock antigens and hypothetical antigens. Strategies for evaluation of novel antigen candidates are discussed critically. Relatively few of the described antigens were evaluated for their use in CMI based diagnostic assays and so far, no obvious candidate has been identified...... to development of antibodies and shedding of detectable amounts of MAP. At present, available diagnostic assays are limited by the lack of MAP specific antigens included in these assays resulting in poor specificity. The objective of this review is to provide a systematic overview of diagnostic MAP antigen...... faeces; however, these diagnostic tools are often not applicable until years after infection. Detection of MAP specific cell-mediated immune (CMI) responses can serve as an alternative and be implemented in a diagnostic tool. CMI responses can be measured at an early stage of infection, prior...

  8. Diagnostic study on the relation between ozone and vorticity potential

    Energy Technology Data Exchange (ETDEWEB)

    Abdel Basset, H. [Department of Astronomy and Meteorology, Faculty of Science, Al Azhar University, Nasr City, Cairo (Egypt); Gahein, A. [Egyptian Meteorological Authority, Cairo (Egypt)

    2003-04-01

    A diagnostic analysis of a Mediterranean system and the associated tropopause folding for the period 27 February to 10 March, 1987 is presented. Geopotential height, potential vorticity (PV) and relative humidity distributions were diagnosed. The analysis indicates clear correlation between the development of the cut-off low and the tropopause folding. A series of vertical cross-sections at the ends of the jet streaks demonstrated that a fold could be captured using potential vorticity and relative humidity. Q-vectors were employed to investigate vertical motion in the vicinity of the fold and showed the exact positions of descent corresponding to the fold along the entire length of the jet streak. The analysis also shows that the strong correlation between total ozone and column integrated vorticity potential holds well for all levels. As both quantities are integrals through the atmosphere, this result is consistent with, but does not prove, a high independent linear dependence between ozone and PV. More case studies are needed to assure the high linear dependence between ozone and PV. The maximum transport of ozone from the stratosphere to the troposphere is coinciding with the maximum developing system, and also with the maximum values of PV. [Spanish] Se presenta un analisis diagnostico de un Sistema mediterraneo y del pliegue de la tropopausa asociado durante el periodo del 27 de febrero al 10 de marzo de 1987. Se diagnosticaron la altitud neopotencial, el potencial de vorticidad y la distribucion de la humedad relativa. El analisis indica una correlacion clara entre el desarrollo de la baja segregada y el pliegue de la tropopausa. Una serie de cortes verticales en los extremos de las trazas del chorro demostraron que el pliegue puede ser capturado utilizando el potencial de vorticidad y la humedad relativa. Para investigar la movilidad vertical en la vecindad del pliegue se utilizaron vectores Q, y se demostraron las posiciones exactas de descenso

  9. Single-cell proteomics: potential implications for cancer diagnostics.

    Science.gov (United States)

    Gavasso, Sonia; Gullaksen, Stein-Erik; Skavland, Jørn; Gjertsen, Bjørn T

    2016-01-01

    Single-cell proteomics in cancer is evolving and promises to provide more accurate diagnoses based on detailed molecular features of cells within tumors. This review focuses on technologies that allow for collection of complex data from single cells, but also highlights methods that are adaptable to routine cancer diagnostics. Current diagnostics rely on histopathological analysis, complemented by mutational detection and clinical imaging. Though crucial, the information gained is often not directly transferable to defined therapeutic strategies, and predicting therapy response in a patient is difficult. In cancer, cellular states revealed through perturbed intracellular signaling pathways can identify functional mutations recurrent in cancer subsets. Single-cell proteomics remains to be validated in clinical trials where serial samples before and during treatment can reveal excessive clonal evolution and therapy failure; its use in clinical trials is anticipated to ignite a diagnostic revolution that will better align diagnostics with the current biological understanding of cancer.

  10. Competitive advantage of diferric transferrin in delivering iron to reticulocytes.

    Science.gov (United States)

    Huebers, H A; Csiba, E; Huebers, E; Finch, C A

    1983-01-01

    Radioiron- and radioiodine-labeled forms of human diferric and monoferric transferrin and apotransferrin, isolated by preparative isoelectric focusing, were used to define transferrin-iron uptake by human reticulocytes. In mixtures of human diferric and monoferric transferrin, the diferric molecule had a constant 7-fold advantage in delivering iron to reticulocytes, as compared with the 2-fold advantage when single solutions of mono- and diferric transferrins were compared. This was shown to be due to competitive interaction in iron delivery, probably at a common membrane-receptor binding site for transferrin. Apotransferrin did not interfere with the iron-donating process and its limited cellular uptake was inhibited in noncompetitive fashion by diferric transferrin. PMID:6572005

  11. Carbohydrate deficient transferrin (CDT) in alcoholic cirrhosis: a kinetic study

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Grønbaek, M; Møller, Søren

    1997-01-01

    BACKGROUND/AIMS: Carbohydrate deficient transferrin has been introduced as a marker of excessive alcohol intake. The present study was undertaken in order to measure the circulating level of carbohydrate deficient transferrin in patients with alcoholic cirrhosis and to assess arteriovenous kinetics...... of carbohydrate deficient transferrin in liver and kidney. METHODS/RESULTS: The median value of serum carbohydrate deficient transferrin was 16.0 U/l in patients with alcoholic cirrhosis (n = 41), and this value was not significantly different from that of a normal control group (median 17.4 U/l, n = 55, ns......). Carbohydrate deficient transferrin was significantly higher in patients with cirrhosis and high current alcohol intake than in abstaining patients (20 vs. 14 U/l, p 50 g/day) had a significantly higher carbohydrate deficient transferrin...

  12. Low serum transferrin correlates with acute-on-chronic organ failure and indicates short-term mortality in decompensated cirrhosis.

    Science.gov (United States)

    Bruns, Tony; Nuraldeen, Renwar; Mai, Martina; Stengel, Sven; Zimmermann, Henning W; Yagmur, Eray; Trautwein, Christian; Stallmach, Andreas; Strnad, Pavel

    2017-02-01

    Iron represents an essential, but potentially harmful micronutrient, whose regulation has been associated with poor outcome in liver disease. Its homeostasis is tightly linked to oxidative stress, bacterial infections and systemic inflammation. To study the prognostic short-term significance of iron parameters in a cohort study of patients with decompensation of cirrhosis at risk of acute-on-chronic liver failure (ACLF). Ferritin, transferrin, iron, transferrin saturation (TSAT) and hepcidin were determined in sera from 292 German patients hospitalized for decompensation of cirrhosis with ascites, of which 78 (27%) had ACLF. Short-term mortality was prospectively assessed 30 and 90 days after inclusion. Transferrin concentrations were significantly lower, whereas ferritin and TSAT were higher in patients with ACLF compared to patients without ACLF (P≤.006). Transferrin, TSAT and ferritin differentially correlated with the severity of organ failure, active alcoholism and surrogates of systemic inflammation and macrophage activation. As compared with survivors, 30-day non-survivors displayed lower serum transferrin (P=.0003) and higher TSAT (P=.003), whereas 90-day non-survivors presented with higher ferritin (P=.03) and lower transferrin (P=.02). Lower transferrin (continuous or dichotomized at 87 mg/dL) and consecutively higher TSAT (continuous or dichotomized >41%) indicated increased mortality within 30 days and remained significant after adjustment for organ failure and inflammation in multivariate regression models and across subgroups of patients. Among the investigated indicators of iron metabolism, serum transferrin concentration was the best indicator of organ failure and an independent predictor of short-term mortality at 30 days. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Elevated transferrin saturation and risk of diabetes

    DEFF Research Database (Denmark)

    Ellervik, Christina; Mandrup-Poulsen, Thomas; Andersen, Henrik Ullits

    2011-01-01

    OBJECTIVE We tested the hypothesis that elevated transferrin saturation is associated with an increased risk of any form of diabetes, as well as type 1 or type 2 diabetes separately. RESEARCH DESIGN AND METHODS We used two general population studies, The Copenhagen City Heart Study (CCHS, N = 9......,121) and The Copenhagen General Population Study (CGPS, N = 24,195), as well as a 1:1 age- and sex-matched population-based case-control study with 6,129 patients with diabetes from the Steno Diabetes Centre and 6,129 control subjects, totaling 8,535 patients with diabetes and 37,039 control subjects. RESULTS...

  14. Chromatographic Monoliths for High-Throughput Immunoaffinity Isolation of Transferrin from Human Plasma

    Directory of Open Access Journals (Sweden)

    Irena Trbojević-Akmačić

    2016-06-01

    Full Text Available Changes in protein glycosylation are related to different diseases and have a potential as diagnostic and prognostic disease biomarkers. Transferrin (Tf glycosylation changes are common marker for congenital disorders of glycosylation. However, biological interindividual variability of Tf N-glycosylation and genes involved in glycosylation regulation are not known. Therefore, high-throughput Tf isolation method and large scale glycosylation studies are needed in order to address these questions. Due to their unique chromatographic properties, the use of chromatographic monoliths enables very fast analysis cycle, thus significantly increasing sample preparation throughput. Here, we are describing characterization of novel immunoaffinity-based monolithic columns in a 96-well plate format for specific high-throughput purification of human Tf from blood plasma. We optimized the isolation and glycan preparation procedure for subsequent ultra performance liquid chromatography (UPLC analysis of Tf N-glycosylation and managed to increase the sensitivity for approximately three times compared to initial experimental conditions, with very good reproducibility. This work is licensed under a Creative Commons Attribution 4.0 International License.

  15. Evidence for low molecular weight, non-transferrin-bound iron in rat brain and cerebrospinal fluid

    DEFF Research Database (Denmark)

    Moos, Torben; Morgan, Evan H.

    1998-01-01

    Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake......Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake...

  16. Development of technique for diagnostics of social reserves of development of collective labour potential

    OpenAIRE

    Голубєв, Станіслав Миколайович

    2015-01-01

    The problems of diagnostics of social reserves of the collective labour potential are considered in the article. The aim of this study is to develop diagnostic techniques of social reserves of the collective labour potential in the work and the essence of the concept of "social reserves" as a subject of study of economics and their features in the study of collective labour potential. The use of these reserves can increase the efficiency of the labour collective processes by improving coopera...

  17. Saliva: Physiology and Diagnostic Potential in Health and Disease

    Directory of Open Access Journals (Sweden)

    Sebastien J. C. Farnaud

    2010-01-01

    Full Text Available Saliva has been described as the mirror of the body. In a world of soaring healthcare costs and an environment where rapid diagnosis may be critical to a positive patient outcome, saliva is emerging as a viable alternative to blood sampling. In this review, we discuss the composition and various physiological roles of saliva in the oral cavity, including soft tissue protection, antimicrobial activities, and oral tissue repair. We then explore saliva as a diagnostic marker of local oral disease and focus particularly on oral cancers. The cancer theme continues when we focus on systemic disease diagnosis from salivary biomarkers. Communicable disease is the focus of the next section where we review the literature relating to the direct and indirect detection of pathogenic infections from human saliva. Finally, we discuss hormones involved in appetite regulation and whether saliva is a viable alternative to blood in order to monitor hormones that are involved in satiety.

  18. Biodistribution of Ru-97-labeled DTPA, DMSA and transferrin

    International Nuclear Information System (INIS)

    Som, P.; Oster, Z.H.; Fairchild, R.G.; Atkins, H.L.; Brill, A.B.; Gil, M.C.; Srivastava, S.C.; Meinken, G.E.; Goldman, A.G.; Richards, P.

    1980-01-01

    Ruthenium-97 is being produced at the Brookhaven Linac Isotope Producer (BLIP). The favorable physical properties of Ru-97 and chemical reactivity of ruthenium offer a potential for using this isotope to label compounds useful for delayed scanning. Diethylenetriamine pentaacetic acid (DTPA), 2,3-Dimercaptosuccinic acid (DMSA), and Transferrin (TF) were labeled with Ru-97-chloride. Ru-97-DTPA and In-111-DTPA, injected intravenously, showed similar organ distribution, kinetics, and more than 80% excretion by 0.5 h. Ru-97-DTPA and In-111-DTPA injected into the cisterna magna of dogs showed similar kinetics in brain, blood, and urinary bladder. The energy deposited by 1 mCi In-111-DTPA is twice that from 1 mCi Ru-97-DTPA. High quality camera images of the CSF space in the dog were obtained with both isotopes. Ru-97-DMSA was prepared with and without the addition of SnCl 2 .2H 2 O. Tin-free DMSA was rapidly excreted via the kidneys, whereas for maximum cortical deposition, the tin-containing preparation was superior. This compound is suitable for delayed imaging of both normal and impaired kidneys. Tissue distribution studies were performed in abscess-bearing rats with Ru-97-transferrin. Although blood levels were higher than with Ga-67-citrate, the abscess had twice as much Ru-97-TF as Ga-67-citrate and the Ru-97 muscle activity was one-third that of Ga-67. Imaging of abscess-bearing rabbits with Ru-97-TF visualized the abscesses as early as 1/2 hr after injection. Since the initial images visualize the abscess so clearly and since the TF portion of the compound binds to the abscess, Tc-99m-TF is being studied for the same purpose. Ru-97-labeled compounds are a promising replacement for In-111 and possibly also for Ga-67 compounds with the advantages of lower radiation dose and high quality image

  19. Diagnostics

    DEFF Research Database (Denmark)

    Donné, A.J.H.; Costley, A.E.; Barnsley, R.

    2007-01-01

    of the measurements—time and spatial resolutions, etc—will in some cases be more stringent. Many of the measurements will be used in the real time control of the plasma driving a requirement for very high reliability in the systems (diagnostics) that provide the measurements. The implementation of diagnostic systems...... on ITER is a substantial challenge. Because of the harsh environment (high levels of neutron and gamma fluxes, neutron heating, particle bombardment) diagnostic system selection and design has to cope with a range of phenomena not previously encountered in diagnostic design. Extensive design and R......&D is needed to prepare the systems. In some cases the environmental difficulties are so severe that new diagnostic techniques are required. The starting point in the development of diagnostics for ITER is to define the measurement requirements and develop their justification. It is necessary to include all...

  20. Actinide uptake by transferrin and ferritin metalloproteins

    International Nuclear Information System (INIS)

    Den Auwer, C.; Llorens, I.; Moisy, Ph.; Vidaud, C.; Goudard, F.; Barbot, C.; Solari, P.L.; Funke, H.

    2005-01-01

    In order to better understand the mechanisms of actinide uptake by specific biomolecules, it is essential to explore the intramolecular interactions between the cation and the protein binding site. Although this has long been done for widely investigated transition metals, very few studies have been devoted to complexation mechanisms of actinides by active chelation sites of metalloproteins. In this field, X-ray absorption spectroscopy has been extensively used as a structural and electronic metal cation probe. The two examples that are presented here are related to two metalloproteins in charge of iron transport and storage in eukaryote cells: transferrin and ferritin. U(VI)O 2 2+ , Np(IV) and Pu(IV) have been selected because of their possible role as contaminant from the geosphere. (orig.)

  1. The Prognostic, Diagnostic, and Therapeutic Potential of Tumor Antigens

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn

    or abundance in cancer cells is often unique and their roles and functions in tumorigenesis are, in many cases, studied extensively. They, therefore, have the potential to be highly specific biomarkers as well as therapeutic targets, but complex analysis combining basic science, high-throughput methods...... of genomics and proteomics, and clinical studies need to be combined. These analyses produce large amounts of data that require advanced bioinformatics methods for collection, management, integration and interpretation. In this thesis, I have explored the potential of tumor antigens as biomarkers...... and therapeutic agents, by developing and implementing several computational tools and databases for immunotherapy target discovery, and have analyzed the potential of tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas. In this analysis I have shown that the combination of proteomics...

  2. Decreased plasma prorenin levels in primary aldosteronism: potential diagnostic implications.

    Science.gov (United States)

    Berge, Constance; Courand, Pierre-Yves; Harbaoui, Brahim; Paget, Vinciane; Khettab, Fouad; Bricca, Giampiero; Fauvel, Jean-Pierre; Lantelme, Pierre

    2015-01-01

    Primary aldosteronism could exert a negative feedback on prorenin secretion, of possibly different magnitude, whether it is related to an aldosterone-producing adenoma (APA) or an idiopathic hyperaldosteronism (IHA). The objectives of this study were to evaluate the level of prorenin in three subgroups: APA, IHA, and essential hypertension; and the performance of the aldosterone-to-prorenin ratio (APR) for the diagnosis of an APA. Seven hundred and forty-six hypertensive patients with a standardized work-up, including a prorenin measurement, were considered. Ninety-six patients without neutral treatment and 38 patients with other forms of secondary hypertension were excluded. APA and IHA were categorized according to computed tomography scan, adrenal venous sampling, pathological analysis and improvement of hypertension after surgery. Thirty-five patients had a diagnosis of APA, 57 of IHA and 504 of essential hypertension. Prorenin was lower in APA and IHA than in essential hypertension (32.9, 40.4 and 50.3  pg/ml, respectively; P < 0.001). APR was higher in patients with APA and IHA than in those with essential hypertension (24.0, 11.8, and 4.0  pmol/l per pg/ml, respectively; P < 0.001). The APR was more discriminant than the aldosterone-to-renin ratio to identify APA compared to IHA (area under the receiver operating curve at 0.750 and 0.639, respectively; P = 0.04). The optimal cut-off values were 22  pmol/l per pg/ml for APR (sensitivity 57.0%, specificity 93.0%) and 440  pmol/l per pg/ml for aldosterone-to-renin ratio (sensitivity 54.3%, specificity 82.5%). Primary aldosteronism and particularly its most caricatural form, that is APA, seems associated with a lower level of prorenin than essential hypertension. The APR could be included in the diagnostic strategy of APA.

  3. Ceruloplasmin/Transferrin Ratio Changes in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Rosanna Squitti

    2011-01-01

    Full Text Available The link between iron and Alzheimer's disease (AD has been mainly investigated with a focus on the local accumulation of this metal in specific areas of the brain that are critical for AD. In the present study, we have instead looked at systemic variations of markers of iron metabolism. We measured serum levels of iron, ceruloplasmin, and transferrin and calculated the transferrin saturation and the ceruloplasmin to transferrin ratio (Cp/Tf. Cp/Tf and transferrin saturation increased in AD patients. Cp/Tf ratios also correlated positively with peroxide levels and negatively with serum iron concentrations. Elevated values of ceruloplasmin, peroxides, and Cp/Tf inversely correlated with MMSE scores. Isolated medial temporal lobe atrophy positively correlated with Cp/Tf and negatively with serum iron. All these findings indicate that the local iron accumulation found in brain areas critical for AD should be viewed in the frame of iron systemic alterations.

  4. Prospective IS-MST radar. Potential and diagnostic capabilities

    Directory of Open Access Journals (Sweden)

    Potekhin A.P.

    2016-09-01

    Full Text Available In the next few years, a new radar is planned to be built near Irkutsk. It should have capabilities of incoherent scatter (IS radars and mesosphere-stratosphere-troposphere (MST radars [Zherebtsov et al., 2011]. The IS-MST radar is a phased array of two separated antenna panels with a multichannel digital receiving system, which allows detailed space-time processing of backscattered signal. This paper describes characteristics, configuration, and capabilities of the antenna and transceiver systems of this radar. We estimate its potential in basic operating modes to study the ionosphere by the IS method at heights above 100 km and the atmosphere with the use of signals scattered from refractive index fluctuations, caused by turbulent mixing at heights below 100 km. The modeling shows that the radar will allow us to regularly measure neutral atmosphere parameters at heights up to 26 km as well as to observe mesosphere summer echoes at heights near 85 km in the presence of charged ice particles (an increase in Schmidt number and mesosphere winter echoes at heights near 65 km with increasing background electron density. Evaluation of radar resources at the IS mode in two height ranges 100–600 and 600–2000 km demonstrates that in the daytime and with the accumulation time of 10 min, the upper boundaries of electron density and ionospheric plasma temperature are ~1500 and ~1300 km respectively, with the standard deviation of no more than 10 %. The upper boundary of plasma drift velocity is ~1100 km with the standard deviation of 45 m/s. The estimation of interferometric capabilities of the MST radar shows that it has a high sensitivity to objects of angular size near 7.5 arc min, and its potential accuracy in determining target angles can reach 40 arc sec.

  5. Acquisition of iron from transferrin regulates reticulocyte heme synthesis

    International Nuclear Information System (INIS)

    Ponka, P.; Schulman, H.M.

    1985-01-01

    Fe-salicylaldehyde isonicotinoylhydrazone (SIH), which can donate iron to reticulocytes without transferrin as a mediator, has been utilized to test the hypothesis that the rate of iron uptake from transferrin limits the rate of heme synthesis in erythroid cells. Reticulocytes take up 59 Fe from [ 59 Fe]SIH and incorporate it into heme to a much greater extent than from saturating concentrations of [ 59 Fe]transferrin. Also, Fe-SIH stimulates [2- 14 C]glycine into heme when compared to the incorporation observed with saturating levels of Fe-transferrin. In addition, delta-aminolevulinic acid does not stimulate 59 Fe incorporation into heme from either [ 59 Fe]transferrin or [ 59 Fe]SIH but does reverse the inhibition of 59 Fe incorporation into heme caused by isoniazid, an inhibitor of delta-aminolevulinic acid synthase. Taken together, these results suggest the hypothesis that some step(s) in the pathway of iron from extracellular transferrin to intracellular protoporphyrin limits the overall rate of heme synthesis in reticulocytes

  6. The physiological significance of transferrin microheterogeneity : an interpretation of the role of N-linked glycans in transferrin and iron metabolism /

    NARCIS (Netherlands)

    G. de Jong (Gerardus)

    1993-01-01

    textabstractThe starting point for this thesis was the observation that when attempts are made to separate monoferric transferrins from diferric transferrin by isoelectric focusing, in addition to what was thought to represent the pure monoferric transferrins, a great number of additional bands

  7. Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India.

    Science.gov (United States)

    Bapat, Prachi R; Satav, Ashish R; Husain, Aliabbas A; Shekhawat, Seema D; Kawle, Anuja P; Chu, Justin J; Purohit, Hemant J; Daginawala, Hatim F; Taori, Girdhar M; Kashyap, Rajpal S

    2015-01-01

    Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

  8. Transferrin targeted core-shell nanomedicine for combinatorial delivery of doxorubicin and sorafenib against hepatocellular carcinoma.

    Science.gov (United States)

    Malarvizhi, Giridharan Loghanathan; Retnakumari, Archana Payickattu; Nair, Shantikumar; Koyakutty, Manzoor

    2014-11-01

    Combinatorial drug delivery is an attractive, but challenging requirement of next generation cancer nanomedicines. Here, we report a transferrin-targeted core-shell nanomedicine formed by encapsulating two clinically used single-agent drugs, doxorubicin and sorafenib against liver cancer. Doxorubicin was loaded in poly(vinyl alcohol) nano-core and sorafenib in albumin nano-shell, both formed by a sequential freeze-thaw/coacervation method. While sorafenib from the nano-shell inhibited aberrant oncogenic signaling involved in cell proliferation, doxorubicin from the nano-core evoked DNA intercalation thereby killing >75% of cancer cells. Upon targeting using transferrin ligands, the nanoparticles showed enhanced cellular uptake and synergistic cytotoxicity in ~92% of cells, particularly in iron-deficient microenvironment. Studies using 3D spheroids of liver tumor indicated efficient penetration of targeted core-shell nanoparticles throughout the tissue causing uniform cell killing. Thus, we show that rationally designed core-shell nanoparticles can effectively combine clinically relevant single-agent drugs for exerting synergistic activity against liver cancer. Transferrin-targeted core-shell nanomedicine encapsulating doxorubicin and sorafenib was studied as a drug delivery system against hepatocellular carcinoma, resulting in enhanced and synergistic therapeutic effects, paving the way towards potential future clinical applications of similar techniques. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Downregulation of transferrin receptor surface expression by intracellular antibody

    International Nuclear Information System (INIS)

    Peng Jilin; Wu Sha; Zhao Xiaoping; Wang Min; Li Wenhan; Shen Xin; Liu Jing; Lei Ping; Zhu Huifen; Shen Guanxin

    2007-01-01

    To deplete cellular iron uptake, and consequently inhibit the proliferation of tumor cells, we attempt to block surface expression of transferrin receptor (TfR) by intracellular antibody technology. We constructed two expression plasmids (scFv-HAK and scFv-HA) coding for intracellular single-chain antibody against TfR with or without endoplasmic reticulum (ER) retention signal, respectively. Then they were transfected tumor cells MCF-7 by liposome. Applying RT-PCR, Western blotting, immunofluorescence microscopy and immunoelectron microscope experiments, we insure that scFv-HAK intrabody was successfully expressed and retained in ER contrasted to the secreted expression of scFv-HA. Flow cytometric analysis confirmed that the TfR surface expression was markedly decreased approximately 83.4 ± 2.5% in scFv-HAK transfected cells, while there was not significantly decrease in scFv-HA transfected cells. Further cell growth and apoptosis characteristics were evaluated by cell cycle analysis, nuclei staining and MTT assay. Results indicated that expression of scFv-HAK can dramatically induce cell cycle G1 phase arrest and apoptosis of tumor cells, and consequently significantly suppress proliferation of tumor cells compared with other control groups. For First time this study demonstrates the potential usage of anti-TfR scFv-intrabody as a growth inhibitor of TfR overexpressing tumors

  10. Proteomic identification of CIB1 as a potential diagnostic factor in ...

    Indian Academy of Sciences (India)

    Proteomic identification of CIB1 as a potential diagnostic factor in hepatocellular carcinoma. Tong Junrong Zhou Huancheng H E Feng Gao Yi Yang Xiaoqin Luo Zhengmao Zhang Hong Zeng Jianying Wang Yin Huang Yuanhang Zhang Jianlin Sun Longhua He Guolin. Articles Volume 36 Issue 4 September 2011 pp 659- ...

  11. Cloning and characterization of transferrin cDNA and rapid detection of transferrin gene polymorphism in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Tange, N; Jong-Young, L; Mikawa, N; Hirono, I; Aoki, T

    1997-12-01

    A cDNA clone of rainbow trout (Oncorhynchus mykiss) transferrin was obtained from a liver cDNA library. The 2537-bp cDNA sequence contained an open reading frame encoding 691 amino acids and the 5' and 3' noncoding regions. The amino acid sequences at the iron-binding sites and the two N-linked glycosylation sites, and the cysteine residues were consistent with known, conserved vertebrate transferrin cDNA sequences. Single N-linked glycosylation sites existed on the N- and C-lobe. The deduced amino acid sequence of the rainbow trout transferrin cDNA had 92.9% identities with transferrin of coho salmon (Oncorhynchus kisutch); 85%, Atlantic salmon (Salmo salar); 67.3%, medaka (Oryzias latipes); 61.3% Atlantic cod (Gadus morhua); and 59.7%, Japanese flounder (Paralichthys olivaceus). The long and accurate polymerase chain reaction (LA-PCR) was used to amplify approximately 6.5 kb of the transferrin gene from rainbow trout genomic DNA. Restriction fragment length polymorphisms (RFLPs) of the LA-PCR products revealed three digestion patterns in 22 samples.

  12. Aluminum stimulates uptake of non-transferrin bound iron and transferrin bound iron in human glial cells

    International Nuclear Information System (INIS)

    Kim, Yongbae; Olivi, Luisa; Cheong, Jae Hoon; Maertens, Alex; Bressler, Joseph P.

    2007-01-01

    Aluminum and other trivalent metals were shown to stimulate uptake of transferrin bound iron and nontransferrin bound iron in erytholeukemia and hepatoma cells. Because of the association between aluminum and Alzheimer's Disease, and findings of higher levels of iron in Alzheimer's disease brains, the effects of aluminum on iron homeostasis were examined in a human glial cell line. Aluminum stimulated dose- and time-dependent uptake of nontransferrin bound iron and iron bound to transferrin. A transporter was likely involved in the uptake of nontransferrin iron because uptake reached saturation, was temperature-dependent, and attenuated by inhibitors of protein synthesis. Interestingly, the effects of aluminum were not blocked by inhibitors of RNA synthesis. Aluminum also decreased the amount of iron bound to ferritin though it did not affect levels of divalent metal transporter 1. These results suggest that aluminum disrupts iron homeostasis in Brain by several mechanisms including the transferrin receptor, a nontransferrin iron transporter, and ferritin

  13. Can a finding of cervical vestibular evoked myogenic potentials contribute to vestibular migraine diagnostics?

    Directory of Open Access Journals (Sweden)

    Tihana Vešligaj

    2016-02-01

    Full Text Available Aim To investigate differences in vestibular evoked myogenic potentials (VEMP results with patients suffering from vestibular migraine and healthy people, taking into consideration values of threshold and latency of occurrence of the characteristic wave complex, size of amplitude, and interaural amplitude ratio. According to the results, determine the importance and usefulness of VEMP in vestibular migraine diagnostics. Methods A total number of 62 subjects were included in the study, 32 of them belonging to a group of patients suffering from vestibular migraine (VM, while other 30 were in a control group of healthy subjects. Information was collected during the diagnostic evaluation. General and otoneurological history of patients and bedside tests, audiological results, videonystagmography and cervical vestibular evoked myogenic potentials (cVEMP were made. Results There was a difference in an interaural ratio of amplitudes in the experimental and control groups, but it was not found to be clinically significant. By ToneBurst 500 Hz method, the interaural amplitude ratio higher than 35% was measured in 46.97% subjects, while the response was totally unilaterally missing in 28.8% patients. Conclusion Even the sophisticated method as cVEMP does not give the ultimate result confirming the vestibular migraine diagnosis, and neither do other diagnostic methods. cVEMP result can contribute to the completion of full mosaic of vestibular migraine diagnostics.

  14. Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake

    International Nuclear Information System (INIS)

    Parab, Harshala J; Huang, Jing-Hong; Liu, Ru-Shi; Lai, Tsung-Ching; Jan, Yi-Hua; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan; Hwu, Yeu-Kuang; Tsai, Din Ping; Chuang, Shih-Yi; Pang, Jong-Hwei S

    2011-01-01

    The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

  15. Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake

    Energy Technology Data Exchange (ETDEWEB)

    Parab, Harshala J; Huang, Jing-Hong; Liu, Ru-Shi [Department of Chemistry, National Taiwan University, Taipei 106, Taiwan (China); Lai, Tsung-Ching; Jan, Yi-Hua; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan [Genomics Research Center, Academia Sinica, Taipei 115, Taiwan (China); Hwu, Yeu-Kuang [Institute of Physics, Academia Sinica, Taipei 115, Taiwan (China); Tsai, Din Ping [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Chuang, Shih-Yi; Pang, Jong-Hwei S, E-mail: rsliu@ntu.edu.tw, E-mail: mhsiao@gate.sinica.edu.tw [Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan (China)

    2011-09-30

    The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

  16. Monocyte transferrin-iron uptake in hereditary hemochromatosis

    International Nuclear Information System (INIS)

    Sizemore, D.J.; Bassett, M.L.

    1984-01-01

    Transferrin-iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe-labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron-loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin-iron uptake by these cells

  17. Serum transferrin levels in children with protein-energy malnutrition

    Directory of Open Access Journals (Sweden)

    Selime Aydoğdu

    2013-03-01

    Full Text Available Objective: Although the diagnosis of patients with severemalnutrition is easy, it is very difficult to recognize patientswith mild and moderate malnutrition. A variety of methodsattempts to develop for early diagnosis of these cases.In this study, we evaluated the serum transferrin and albuminlevels in children with mild, moderate and severeprotein-energy malnutrition (PEM.Materials and methods: Children admitted to our policlinic,aged between 3 and 25 months, 45 subjects withPEM and 39 healthy subjects (control group were evaluated.According to the Gomez, Waterlow and Kanawatisubjects with PEM were divided in 3 subgroups mild,moderate and severe PEM. Anthropometric measurementsand biochemical results of 4 groups were compared.Results: For albumin levels in mild to moderate PEMgroups, 37.7% sensitivity, and 28.5% specificity, positivepredictive value 54%; negative predictive value 16.6%was found. For severe PEM sensitivity, specificity, positivepredictive value and negative predictive value were71%, 62.5%, 45%, and 83.3% respectively.With respect to the levels of transferrin, a significant differencewas found between mild PEM-control and moderatePEM-control groups (p0.05.Conclusion: Our study results showed that albumin isa weak indicator in mild-moderate PEM. In these cases,serum transferrin level reduces before decreasing of albuminlevel, thus it may be an early sensitive finding thatcan be used as a sensitive parameter in the diagnosis ofearly stages of malnutrition.Key words: Protein energy malnutrition, children, albumin,transferrin

  18. Isoforms of transferrin in psoriasis patients abusing alcohol

    NARCIS (Netherlands)

    P. Hoefkens (Peter); E.M. Higgins; R.J. Ward (Roberta); H.G. van Eijk (Henk)

    1997-01-01

    textabstractThe different isoforms of transferrin have been quantified by isoelectric focusing in the sera of psoriasis patients with and without a history of abusing alcohol. In both male and female psoriasis subjects abusing alcohol, there were significant increases in the

  19. Nonrandom distribution of iron in circulating human transferrin.

    Science.gov (United States)

    Zak, O; Aisen, P

    1986-07-01

    By combining the urea gel electrophoresis technique of Makey and Seal with Western immunoblotting, a method has been developed for analyzing the distribution of iron between the two sites of circulating human transferrin. The new method avoids exposure of samples to a nonphysiologic pH that may promote removal or redistribution of iron from the protein; this facilitates examination of multiple samples at one time. Analysis of 21 freshly drawn specimens from normal human subjects confirms previous reports that iron is not randomly distributed in the specific sites of transferrin. Rather, there is a considerable range in the ratio of occupancies of N-terminal and C-terminal sites (N:C ratio), from 0.31 to 6.87 in the present study, with the N-terminal site predominantly occupied in most subjects. The N:C ratio correlates modestly with serum iron concentration (r = .54). Possible flaws in studies indicating a random occupancy of the specific sites of circulating transferrin may lie in the low pH to which samples may be exposed during procedures based on isoelectric focusing or in drawing inferences from data considering only total monoferric transferrin rather than the two distinguishable monoferric species.

  20. Potential diagnostic value of serum p53 antibody for detecting colorectal cancer: A meta-analysis.

    Science.gov (United States)

    Meng, Rongqin; Wang, Yang; He, Liang; He, Yuanqing; Du, Zedong

    2018-04-01

    Numerous studies have assessed the diagnostic value of serum p53 (s-p53) antibody in patients with colorectal cancer (CRC); however, results remain controversial. The present study aimed to comprehensively and quantitatively summarize the potential diagnostic value of s-p53 antibody in CRC. The present study utilized databases, including PubMed and EmBase, systematically regarding s-p53 antibody diagnosis in CRC, accessed on and prior to 31 July 2016. The quality of all the included studies was assessed using quality assessment of studies of diagnostic accuracy (QUADAS). The result of pooled sensitivity, pooled specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were analyzed and compared with overall accuracy measures using diagnostic odds ratios (DORs) and area under the curve (AUC) analysis. Publication bias and heterogeneity were also assessed. A total of 11 trials that enrolled a combined 3,392 participants were included in the meta-analysis. Approximately 72.73% (8/11) of the included studies were of high quality (QUADAS score >7), and all were retrospective case-control studies. The pooled sensitivity was 0.19 [95% confidence interval (CI), 0.18-0.21] and pooled specificity was 0.93 (95% CI, 0.92-0.94). Results also demonstrated a PLR of 4.56 (95% CI, 3.27-6.34), NLR of 0.78 (95% CI, 0.71-0.85) and DOR of 6.70 (95% CI, 4.59-9.76). The symmetrical summary receiver operating characteristic curve was 0.73. Furthermore, no evidence of publication bias or heterogeneity was observed in the meta-analysis. Meta-analysis data indicated that s-p53 antibody possesses potential diagnostic value for CRC. However, discrimination power was somewhat limited due to the low sensitivity.

  1. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions.

    Science.gov (United States)

    Valent, Peter; Orazi, Attilio; Steensma, David P; Ebert, Benjamin L; Haase, Detlef; Malcovati, Luca; van de Loosdrecht, Arjan A; Haferlach, Torsten; Westers, Theresia M; Wells, Denise A; Giagounidis, Aristoteles; Loken, Michael; Orfao, Alberto; Lübbert, Michael; Ganser, Arnold; Hofmann, Wolf-Karsten; Ogata, Kiyoyuki; Schanz, Julie; Béné, Marie C; Hoermann, Gregor; Sperr, Wolfgang R; Sotlar, Karl; Bettelheim, Peter; Stauder, Reinhard; Pfeilstöcker, Michael; Horny, Hans-Peter; Germing, Ulrich; Greenberg, Peter; Bennett, John M

    2017-09-26

    Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms characterized by peripheral cytopenia, dysplasia, and a variable clinical course with about 30% risk to transform to secondary acute myeloid leukemia (AML). In the past 15 years, diagnostic evaluations, prognostication, and treatment of MDS have improved substantially. However, with the discovery of molecular markers and advent of novel targeted therapies, new challenges have emerged in the complex field of MDS. For example, MDS-related molecular lesions may be detectable in healthy individuals and increase in prevalence with age. Other patients exhibit persistent cytopenia of unknown etiology without dysplasia. Although these conditions are potential pre-phases of MDS they may also transform into other bone marrow neoplasms. Recently identified molecular, cytogenetic, and flow-based parameters may add in the delineation and prognostication of these conditions. However, no generally accepted integrated classification and no related criteria are as yet available. In an attempt to address this challenge, an international consensus group discussed these issues in a working conference in July 2016. The outcomes of this conference are summarized in the present article which includes criteria and a proposal for the classification of pre-MDS conditions as well as updated minimal diagnostic criteria of MDS. Moreover, we propose diagnostic standards to delineate between ´normal´, pre-MDS, and MDS. These standards and criteria should facilitate diagnostic and prognostic evaluations in clinical studies as well as in clinical practice.

  2. Molecular biomarkers have the potential to improve the diagnostic work-up of pancreatic cystic lesions

    DEFF Research Database (Denmark)

    Plougmann, Julie Isabelle; Klausen, Pia; Karstensen, John Gásdal

    2017-01-01

    of diagnostic tools are used to predict the malignant potential of these cysts, but specificity and sensitivity are limited. Thus, many patients undergo unnecessary operations for benign cysts. Balancing the risks of watchful waiting with those of operative management is key in managing these lesions. During...... the last decade, genetic changes of pancreatic cysts have been examined extensively to estimate their malignant potential. In this review, we provide an overview of the latest molecular and genetic aspects of pancreatic cysts and how they may contribute to the differential diagnosis in patients...

  3. In Silico discovery of transcription factors as potential diagnostic biomarkers of ovarian cancer

    KAUST Repository

    Kaur, Mandeep

    2011-09-19

    Background: Our study focuses on identifying potential biomarkers for diagnosis and early detection of ovarian cancer (OC) through the study of transcription regulation of genes affected by estrogen hormone.Results: The results are based on a set of 323 experimentally validated OC-associated genes compiled from several databases, and their subset controlled by estrogen. For these two gene sets we computationally determined transcription factors (TFs) that putatively regulate transcription initiation. We ranked these TFs based on the number of genes they are likely to control. In this way, we selected 17 top-ranked TFs as potential key regulators and thus possible biomarkers for a set of 323 OC-associated genes. For 77 estrogen controlled genes from this set we identified three unique TFs as potential biomarkers.Conclusions: We introduced a new methodology to identify potential diagnostic biomarkers for OC. This report is the first bioinformatics study that explores multiple transcriptional regulators of OC-associated genes as potential diagnostic biomarkers in connection with estrogen responsiveness. We show that 64% of TF biomarkers identified in our study are validated based on real-time data from microarray expression studies. As an illustration, our method could identify CP2 that in combination with CA125 has been reported to be sensitive in diagnosing ovarian tumors. 2011 Kaur et al; licensee BioMed Central Ltd.

  4. In Silico discovery of transcription factors as potential diagnostic biomarkers of ovarian cancer

    KAUST Repository

    Kaur, Mandeep; MacPherson, Cameron R; Schmeier, Sebastian; Narasimhan, Kothandaraman; Choolani, Mahesh; Bajic, Vladimir B.

    2011-01-01

    Background: Our study focuses on identifying potential biomarkers for diagnosis and early detection of ovarian cancer (OC) through the study of transcription regulation of genes affected by estrogen hormone.Results: The results are based on a set of 323 experimentally validated OC-associated genes compiled from several databases, and their subset controlled by estrogen. For these two gene sets we computationally determined transcription factors (TFs) that putatively regulate transcription initiation. We ranked these TFs based on the number of genes they are likely to control. In this way, we selected 17 top-ranked TFs as potential key regulators and thus possible biomarkers for a set of 323 OC-associated genes. For 77 estrogen controlled genes from this set we identified three unique TFs as potential biomarkers.Conclusions: We introduced a new methodology to identify potential diagnostic biomarkers for OC. This report is the first bioinformatics study that explores multiple transcriptional regulators of OC-associated genes as potential diagnostic biomarkers in connection with estrogen responsiveness. We show that 64% of TF biomarkers identified in our study are validated based on real-time data from microarray expression studies. As an illustration, our method could identify CP2 that in combination with CA125 has been reported to be sensitive in diagnosing ovarian tumors. 2011 Kaur et al; licensee BioMed Central Ltd.

  5. Transferrin variation and genetic structure of reindeer populations in Scandinavia

    Directory of Open Access Journals (Sweden)

    Knut H. Røed

    1987-06-01

    Full Text Available Polyacrylamide gel electrophoresis was used to analyse transferrin variation in herds of semi-domestic reindeer from Scandinavia. The results are compared with previously reported values for other populations of both semi-domestic and wild reindeer using the same techniques as in the present study. In all populations the number of alleles was high, ranging from seven to eleven, and the heterozygosity was correspondingly high, with a mean of 0.749. This high genetic variation in all populations suggests that inbreeding is not widespread among Scandinavian reindeer. The pattern of allele frequency distribution indicates a high degree of genetic heterogeneity in the transferrin locus, both between the different semi-domestic herds and between the different wild populations. The mean value of genetic distance was 0.069 between semi-domestic herds and 0.091 between wild populations. Between semi-domestic and wild populations the genetic distance was particularly high, with a mean of 0.188. This high value was mainly due to a different pattern in the distribution of the two most common transferrin alleles: Tfu was most common among semi-domestic herds, while TfEI was most common among wild populations. These differences in transferrin allele distribution are discussed in relation to possible different origins of semi-domestic and wild reindeer in Scandinavia, or alternatively, to different selection forces acting on transferrin genotypes in semi-domestic and wild populations.Transferrin-variasjon og genetisk struktur hos rein i Skandinavia.Abstact in Norwegian / Sammendrag: Transferrin-variasjon i tamreinflokker ble analysert ved hjelp av polyacrylamid gel elektroforese. Resultatene er sammenlignet med verdier som tidligere er beskrevet for både tamrein og villrein hvor det ble benyttet samme metode som i denne undersøkelsen. I alle populasjonene ble det registrert et høyt antall alleler (7-11 og heterozygositeten var tilsvarende høy med en

  6. DIFFERENTIAL DIAGNOSTICS MODEL RESEARCH BY MEANS OF THE POTENTIAL FUNCTIONS METHOD FOR NEUROLOGY DISEASES CLASSIFICATION

    Directory of Open Access Journals (Sweden)

    V. Z. Stetsyuk

    2016-10-01

    Full Text Available Informatization in medicine offers a lot of opportunities to enhance quality of medical support, accuracy of diagnosis and provides the use of accumulated experience. Modern program systems are utilized now as additional tools to get appropriate advice. This article offers the way to provide help for neurology department doctor of NCSH «OKHMATDYT» during diagnosis determining. It was decided to design the program system for this purpose based on differential diagnostic model. The key problems in differential diagnosis are symptoms similarity between each other in one disease group and the absence of key symptom. Therefore the differential diagnostic model is needed. It is constructed using the potential function method in characteristics space. This characteristics space is formed by 100-200 points - patients with their symptoms. The main feature of this method here is that the decision function is building during recognition step united with learning that became possible with the help of modern powerful computers.

  7. Transferrin-modified liposome promotes α-mangostin to penetrate the blood-brain barrier.

    Science.gov (United States)

    Chen, Zhi-Lan; Huang, Man; Wang, Xia-Rong; Fu, Jun; Han, Min; Shen, You-Qing; Xia, Zheng; Gao, Jian-Qing

    2016-02-01

    α-Mangostin (α-M) is a polyphenolic xanthone that protects and improves the survival of cerebral cortical neurons against Aβ oligomer-induced toxicity in rats. α-M is a potential candidate as a treatment for Alzheimer's disease (AD). However, the efficacy was limited by the poor penetration of the drug through the blood-brain barrier (BBB). In this study, we modified the α-M liposome with transferrin (Tf) and investigated the intracellular distribution of liposomes in bEnd3 cells. In addition, the transport of α-M across the BBB in the Tf(α-M) liposome group was examined. In vitro studies demonstrated that the Tf(α-M) liposome could cross the BBB in the form of an integrated liposome. Results of the in vivo studies on the α-M distribution in the brain demonstrated that the Tf(α-M) liposome improved the brain delivery of α-M. These results indicated that the Tf liposome is a potential carrier of α-M against AD. The use of α-Mangostin (α-M) as a potential agent to treat Alzheimer's disease (AD) has been reported. However, its use is limited by the poor penetration through the blood brain barrier. The delivery of this agent by transferrin-modified liposomes was investigated by the authors in this study. The positive results could point to a better drug delivery system for brain targeting. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. POTENTIALITIES OF DIAGNOSTICS AND DIFFERENTIAL DIAGNOSTICS OF STOMACH DISEASES BY MEANS OF USAGE OF HIGH-PERFORMANCE BLOOD SERUM LIQUID CHROMATOGRAPHY

    Directory of Open Access Journals (Sweden)

    O.P. Alexeeva

    2008-12-01

    Full Text Available 62 patients with the endoscopically and morphologicallyverified diagnosis of the chronic gastritis, 89 patients with the morphologically verified diagnosis of stomach cancer and 43 healthy persons ages 23 to 54 years have been examined. Potentialities of the usage of high-performance blood serum liquid chromatography have been studied for the purpose of diagnostics and differential diagnostics of chronic gastritis and stomach cancer. Blood serum driedextract was investigated by means of"Milichrome A02"chromatograph (Novosibirsk, "Econova" joint-stock company. The chromatograms were treated by the multivahate cluster analysis with the formation of pathologic three-dimensional characteristic state notably differed from the healthy human image. Diagnostic sensitivity of chronic gastritis and stomach cancer acounts for accordingly 92% and 96%. Diagnostic accuracy of the method comes to 94%.

  9. Mining for diagnostic information in body surface potential maps: A comparison of feature selection techniques

    Directory of Open Access Journals (Sweden)

    McCullagh Paul J

    2005-09-01

    Full Text Available Abstract Background In body surface potential mapping, increased spatial sampling is used to allow more accurate detection of a cardiac abnormality. Although diagnostically superior to more conventional electrocardiographic techniques, the perceived complexity of the Body Surface Potential Map (BSPM acquisition process has prohibited its acceptance in clinical practice. For this reason there is an interest in striking a compromise between the minimum number of electrocardiographic recording sites required to sample the maximum electrocardiographic information. Methods In the current study, several techniques widely used in the domains of data mining and knowledge discovery have been employed to mine for diagnostic information in 192 lead BSPMs. In particular, the Single Variable Classifier (SVC based filter and Sequential Forward Selection (SFS based wrapper approaches to feature selection have been implemented and evaluated. Using a set of recordings from 116 subjects, the diagnostic ability of subsets of 3, 6, 9, 12, 24 and 32 electrocardiographic recording sites have been evaluated based on their ability to correctly asses the presence or absence of Myocardial Infarction (MI. Results It was observed that the wrapper approach, using sequential forward selection and a 5 nearest neighbour classifier, was capable of choosing a set of 24 recording sites that could correctly classify 82.8% of BSPMs. Although the filter method performed slightly less favourably, the performance was comparable with a classification accuracy of 79.3%. In addition, experiments were conducted to show how (a features chosen using the wrapper approach were specific to the classifier used in the selection model, and (b lead subsets chosen were not necessarily unique. Conclusion It was concluded that both the filter and wrapper approaches adopted were suitable for guiding the choice of recording sites useful for determining the presence of MI. It should be noted however

  10. New developments in JET neutron, alpha particle and fuel mixture diagnostics with potential relevance to ITER

    International Nuclear Information System (INIS)

    Murari, A.; Bertalot, L.; Angelone, M.; Pillon, M.; Ericsson, G.; Conroy, S.; Kaellne, J.; Kiptily, V.; Popovichev, S.; Adams, J.M.; Stork, D.; Afanasyiev, V.; Mironov, M.; Bonheure, G.

    2005-01-01

    Some recent JET campaigns, with the introduction of trace amount (n T /n D 4 He, provided unique opportunities to test new diagnostic approaches and technologies for the detection of neutrons, alpha particles and fuel mixture. With regard to neutron detection, the recent activity covered all the most essential aspects: calibration and cross validation of the diagnostics, measurement of the spatial distribution of the neutrons, particle transport and finally neutron spectrometry. The first tests of some new neutron detection technologies were also undertaken successfully during the TTE campaign. To improve JET diagnostic capability in the field of alpha particles, a strong development program was devoted to the measurement of their slowing down and imaging with gamma ray spectroscopy. A new approach for the fusion community to measure the fast ion losses, based on the activation technique, was also successfully attempted for the first time on JET. A careful assessment of the NPA potential to determine the fuel mixture and the particle transport coefficients is under way. (author)

  11. Effect of transferrin saturation on internal iron exchange

    International Nuclear Information System (INIS)

    Bergamaschi, G.; Eng, M.J.; Huebers, H.A.; Finch, C.A.

    1986-01-01

    Radioiron was introduced into the intestinal lumen to evaluate absorption, injected as nonviable red cells to evaluate reticuloendothelial (RE) processing of iron, and injected as hemoglobin to evaluate hepatocyte iron processing. Redistribution of iron through the plasma was evaluated in control animals and animals whose transferrin was saturated by iron infusion. Radioiron introduced into the lumen of the gut as ferrous sulfate and as transferrin-bound iron was absorbed about half as well in iron-infused animals, and absorbed iron was localized in the liver. The similar absorption of transferrin-bound iron suggested that absorption of ferrous iron occurred via the mucosal cell and did not enter by diffusion. The decrease in absorption was associated with an increase in mucosal iron and ferritin content produced by the iron infusion. An inverse relationship (r = -0.895) was shown between mucosal ferritin iron and absorption. When iron was injected as nonviable red cells, it was deposited predominantly in reticuloendothelial cells of the spleen. Return of this radioiron to the plasma was only 6% of that in control animals. While there was some movement of iron from spleen to liver, this could be accounted for by intravascular hemolysis. Injected hemoglobin tagged with radioiron was for the most part taken up and held by the liver. Some 13% initially localized in the marrow in iron-infused animals was shown to be storage iron unavailable for hemoglobin synthesis. These studies demonstrate the hepatic trapping of absorbed iron and the inability of either RE cell or hepatocyte to release iron in the transferrin-saturated animal

  12. Diagnostic accuracy of clinical and blood examination for sepsis in potentially infected neonates

    Directory of Open Access Journals (Sweden)

    Ari Mulyani

    2006-10-01

    Full Text Available Background Neonatal sepsis remains a diagnostic challenge due to its nonspesific symptoms and signs. Blood culture as the gold standard is still a problem because it takes time, is expensive, and not every health facility is able to perionn. Objective To evaluate the diagnostic accuracy of clinical symptoms, hematologic findings, and C-reactive protein (CRP in neonatal sepsis. Methods Samples were taken from potentially infected neonates admitted to the Matemal-Perinatal Unit of Sardjito Hospital, between December 1st, 2000 and March 31st, 2001 using at least one of the criteria: prematurity, very low birth weight infants, matemal pyrexia during delivery, premature membrane rupture, or thick, cloudy amniotic fluid. Clinical symptoms, total leukocyte, neutrophil, platelet count, CRP, and blood culture as the gold standard were examined. Results Among 99 neonates enrolled, the sensitivity, specificity, positive and negative predictive value of clinical symptoms were 79.3%, 75.7%, 57.5%, and 89.9%, respectively; leukopenia/leukocytosis were 27.6%, 85.7%, 44.4%, and 74.1%; neutropenia! neutrophilia were 41.4%, 71.4%, 37.5%, and 74.6%; thrombocytopenia were 79.3%, 51.8%, 40.4%, and 85.7%; positive CRP were 58.6%,78.6%,53.1%, and 82.1%. Parallel tests increased the sensitivity up to 89.7%. Specificity, positive and negative predictive value, and likelihood ratio were 44.3%, 40%, 91.2%, and 1.6, respectively. Serial tests increased the specificity up to 88.6%. Sensitivity, positive and negative predictive value, and likelihood ratio were 58.6%, 68%, 83.8%, and 5.1, respectively. Conclusion Clinical sepsis, thrombocytopenia, and CRP are sufficiently accurate as diagnostic tests for sepsis in potentially infected neonates. Parallel tests will increase the sensitivity, while serial tests increase the specificity.

  13. Development and optimization of transferrin-conjugated nanostructured lipid carriers for brain delivery of paclitaxel using Box-Behnken design.

    Science.gov (United States)

    Emami, Jaber; Rezazadeh, Mahboubeh; Sadeghi, Hojjat; Khadivar, Khashayar

    2017-05-01

    The treatment of brain cancer remains one of the most difficult challenges in oncology. The purpose of this study was to develop transferrin-conjugated nanostructured lipid carriers (Tf-NLCs) for brain delivery of paclitaxel (PTX). PTX-loaded NLCs (PTX-NLCs) were prepared using solvent evaporation method and the impact of various formulation variables were assessed using Box-Behnken design. Optimized PTX-NLC was coupled with transferrin as targeting ligand and in vitro cytotoxicity of it was investigated against U-87 brain cancer cell line. As a result, 14.1 mg of cholesterol, 18.5 mg of triolein, and 0.5% poloxamer were used to prepare the optimal formulation. Mean particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug loading (DL), mean release time (MRT) of adopted formulation were confirmed to be 205.4 ± 11 nm, 25.7 ± 6.22 mV, 91.8 ± 0.5%, 5.38 ± 0.03% and 29.3 h, respectively. Following conjugation of optimized PTX-NLCs with transferrin, coupling efficiency was 21.3 mg transferrin per mmol of stearylamine; PS and MRT were increased while ZP, EE and DL decreased non-significantly. Tf-PTX-NLCs showed higher cytotoxic activity compared to non-targeted NLCs and free drug. These results indicated that the Tf-PTX-NLCs could potentially be exploited as a delivery system in brain cancer cells.

  14. The Y4-RNA fragment, a potential diagnostic marker, exists in saliva

    Directory of Open Access Journals (Sweden)

    Tatsuya Ishikawa

    2017-06-01

    Full Text Available The 94-nt full-length Y4-RNA is thought to have roles in the initiation of DNA replication and RNA quality control. Although its 31/32-nt fragment also exists abundantly in plasma, little is known about its physiological role. Since the 31/32-nt Y4-RNA fragment in sera is reported to be more abundant in patients with coronary artery disease than healthy persons, the fragment may have a potential for a diagnostic and/or prognostic biomarker for some diseases regardless of its functionality. As a step toward further investigation of its potential utility, we examined if the 31/32-nt Y4-RNA fragment also exists in saliva that can be obtained noninvasively, and showed that, in addition to the 31/32-nt fragment, 14- and 11-nt Y4-RNA fragments are present in all saliva RNA samples from four healthy persons. We established a PCR method to accurately quantitate the amount of the 31/32-nt Y4-RNA fragment, and estimated its amount in saliva of healthy persons to be 0.06 ± 0.04 fmol per nanogram of saliva RNA. We also tried to develop an easier quantitation method using a DNA molecular beacon. Keywords: Y4-RNA fragment, Saliva RNA, Diagnostic/prognostic marker, Next-generation sequencing, RT-PCR, Molecular beacon

  15. The potential diagnostic power of circulating tumor cell analysis for non-small-cell lung cancer.

    Science.gov (United States)

    Ross, Kirsty; Pailler, Emma; Faugeroux, Vincent; Taylor, Melissa; Oulhen, Marianne; Auger, Nathalie; Planchard, David; Soria, Jean-Charles; Lindsay, Colin R; Besse, Benjamin; Vielh, Philippe; Farace, Françoise

    2015-01-01

    In non-small-cell lung cancer (NSCLC), genotyping tumor biopsies for targetable somatic alterations has become routine practice. However, serial biopsies have limitations: they may be technically difficult or impossible and could incur serious risks to patients. Circulating tumor cells (CTCs) offer an alternative source for tumor analysis that is easily accessible and presents the potential to identify predictive biomarkers to tailor therapies on a personalized basis. Examined here is our current knowledge of CTC detection and characterization in NSCLC and their potential role in EGFR-mutant, ALK-rearranged and ROS1-rearranged patients. This is followed by discussion of the ongoing issues such as the question of CTC partnership as diagnostic tools in NSCLC.

  16. Transferrin receptors on human reticulocytes: variation in site number in hematologic disorders

    International Nuclear Information System (INIS)

    Shumak, K.H.; Rachkewich, R.A.

    1984-01-01

    Assays of binding of 125iodine-labeled ( 125 I) human transferrin were used to study transferrin receptor sites on reticulocytes from 15 normal subjects and from 66 patients with various hematologic disorders. In normal subjects, few or no transferrin receptors were detected whereas the average number of receptors per reticulocyte varied greatly from patient to patient, ranging from 0 to 67,700 in samples, from 35 patients, on which Scatchard analysis of binding of [ 125 I]-transferrin was done. Marked heterogeneity in the number of reticulocyte transferrin receptors in different hematologic disorders was also found in assays with [ 125 I]-OKT9 (monoclonal antibody to the human transferrin receptor). The number of receptors was not correlated with either the reticulocyte count or the hemoglobin

  17. Long interspersed nuclear element-1 hypomethylation and oxidative stress: correlation and bladder cancer diagnostic potential.

    Directory of Open Access Journals (Sweden)

    Maturada Patchsung

    Full Text Available Although, increased oxidative stress and hypomethylation of long interspersed nuclear element-1 (LINE-1 associate with bladder cancer (BCa development, the relationship between these alterations is unknown. We evaluated the oxidative stress and hypomethylation of the LINE-1 in 61 BCa patients and 45 normal individuals. To measure the methylation levels and to differentiate the LINE-1 loci into hypermethylated, partially methylated and hypomethylated, peripheral blood cells, urinary exfoliated cells and cancerous tissues were evaluated by combined bisulfite restriction analysis PCR. The urinary total antioxidant status (TAS and plasma protein carbonyl content were determined. The LINE-1 methylation levels and patterns, especially hypomethylated loci, in the blood and urine cells of the BCa patients were different from the levels and patterns in the healthy controls. The urinary TAS was decreased, whereas the plasma protein carbonyl content was increased in the BCa patients relative to the controls. A positive correlation between the methylation of LINE-1 in the blood-derived DNA and urinary TAS was found in both the BCa and control groups. The urinary hypomethylated LINE-1 loci and the plasma protein carbonyl content provided the best diagnostic potential for BCa prediction. Based on post-diagnostic samples, the combination test improved the diagnostic power to a sensitivity of 96% and a specificity of 96%. In conclusion, decreased LINE-1 methylation is associated with increased oxidative stress both in healthy and BCa subjects across the various tissue types, implying a dose-response association. Increases in the LINE-1 hypomethylation levels and the number of hypomethylated loci in both the blood- and urine-derived cells and increase in the oxidative stress were found in the BCa patients. The combination test of the urinary hypomethylated LINE-1 loci and the plasma protein carbonyl content may be useful for BCa screening and monitoring of

  18. Productivity Analysis of the Botosani Karakul Sheep Depending on the Genetic Types of Serum Transferrin

    Directory of Open Access Journals (Sweden)

    Gheorghe Hrincă

    2011-05-01

    Full Text Available The paper analyzes the sheep productivity of the Botosani Karakul breed in relation to their belonging in different transferrin genotypes. Thirteen electrophoretic phenotypes of transferrin have been identified in this breed. Experimental results show that it is possible to establish correlations between genetic types of serum transferrin and quantitative characteristics of production (meat, wool, milk in this breed depending on age and sex of animals. In lambs, the values of the productive parameters are more grouped in most transferrin genotypes, while in adult animals, more important differentiations of productivity occur among different transferrin genotypes. In adult animals, the productive differentiation among the genotypes Tf is more obvious in rams than in ewes. Irrespective of age and sex, the differences of productivity among transferrin genotypes, in their reciprocity, seldom present significant statistical assurance, a relatively frequent part of them is situated near the first critical threshold of significance, and most of them are unsignificant. Thus, a certain production metabolism is characteristic to each genotype transferrin. But the transferrin genotypes which enhance the sheep productivity, those that differ significantly from the rest of transferrin genotypes, deserve to be taken into account, in the selection works of this breed for its productive improvement.

  19. Iron exchange between transferrin molecules mediated by phosphate compounds and other cell metabolites.

    Science.gov (United States)

    Morgan, E H

    1977-08-25

    The ability of a large number of cellular metabolites to release iron from transferrin was investigated by measuring the rate at which they could mediate iron exchange between two types of transferrin. Rabbit transferrin labelled with 59Fe was incubated with human apotransferrin in the presence of the metabolites. After varying periods of incubation the human transferrin was separated from the rabbit transferrin by immunoprecipitation. GTP, 2,3-diphosphoglycerate, ATP, ADP and citrate produced the most rapid exchange of iron between the two types of transferrin, but many other compounds showed some degree of activity. Iron exchange mediated by the organic phosphates had the characteristics of a single first-order reaction and was sensitive to changes of incubation temperature and pH. The activation energy for the exchange reaction was approx. 13 kcal/mol. The rate of iron exchange from the oxalate - iron - transferrin complex was much lower than from bicarbonate - iron - transferrin. It is concluded that several organic phosphates have the capacity of releasing iron from transferrin. These compounds may represent the means by which the iron is released during the process of cellular uptake.

  20. Fine needle aspiration cytology of IgG4-related disease: A potential diagnostic pitfall?

    Science.gov (United States)

    Kaur, Rajwant; Mitra, Suvradeep; Rajwanshi, Arvind; Das, Ashim; Nahar Saikia, Uma; Dey, Pranab

    2017-01-01

    IgG4-related disease (IgG4-RD) is a tumefactive fibro-inflammatory lesion that can affect any organ system in the body. Till date, no cytological data on IgG4-RD are available and this is the first study depicting the cytopathology features of IgG4-RD. To describe the cytopathological features and potential diagnostic errors of IgG4-RD. The cytological features of 10 histopathology proven IgG4-RD cases (11 samples) were retrospectively reviewed along with corresponding histopathology. The cellularity of the cytology smears was low (36.4%) to moderate (45.4%) to high (18.1%). The low cellularity correlated well with the pattern C in histopathology (predominant fibrosis pattern). The non-epithelial background showed a preponderance of lymphocytes along with polymorphs and spindle-shaped fibroblasts. Most of these cases showed the presence of plasma cells and eosinophils. Epithelial atypia was seen in 18.2% cases. The causes of misdiagnosis were low cellularity, epithelial atypia, and non-representative background. The important diagnostic clues to suspect a diagnosis of IgG4-RD include low cellularity despite adequate effort, inflammatory background rich in lymphocytes and spindle cells admixed with a few plasma cells and eosinophils along with radiological features and raised serum IgG4 Diagn. Cytopathol. 2017;45:14-21. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Current and Potential Developments of Cortisol Aptasensing towards Point-of-Care Diagnostics (POTC

    Directory of Open Access Journals (Sweden)

    Azrul Syafiq Zainol Abidin

    2017-05-01

    Full Text Available Anxiety is a psychological problem that often emerges during the normal course of human life. The detection of anxiety often involves a physical exam and a self-reporting questionnaire. However, these approaches have limitations, as the data might lack reliability and consistency upon application to the same population over time. Furthermore, there might be varying understanding and interpretations of the particular question by the participant, which necessitating the approach of using biomarker-based measurement for stress diagnosis. The most prominent biomarker related to stress, hormone cortisol, plays a key role in the fight-or-flight situation, alters the immune response, and suppresses the digestive and the reproductive systems. We have taken the endeavour to review the available aptamer-based biosensor (aptasensor for cortisol detection. The potential point-of-care diagnostic strategies that could be harnessed for the aptasensing of cortisol were also envisaged.

  2. Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker

    International Nuclear Information System (INIS)

    Allen, John; Murray, Alan; Di Maria, Costanzo; Newton, Julia L

    2012-01-01

    Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed. The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue. In this study we explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing. Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70°). Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beat-to-beat pulse wave analysis. A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002). There were no significant differences between subject groups for the AMP measure at any site. Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05). Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81. Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%. Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls. (paper)

  3. Temperature measurement by thermal strain imaging with diagnostic power ultrasound, with potential for thermal index determination.

    Science.gov (United States)

    Liang, Hai-Dong; Zhou, Li-Xia; Wells, Peter N T; Halliwell, Michael

    2009-05-01

    Over the years, there has been a substantial increase in acoustic exposure in diagnostic ultrasound as new imaging modalities with higher intensities and frame rates have been introduced; and more electronic components have been packed into the probe head, so that there is a tendency for it to become hotter. With respect to potential thermal effects, including those which may be hazardous occurring during ultrasound scanning, there is a correspondingly growing need for in vivo techniques to guide the operator as to the actual temperature rise occurring in the examined tissues. Therefore, an in vivo temperature estimator would be of considerable practical value. The commonly-used method of tissue thermal index (TI) measurement with a hydrophone in water could underestimate the actual value of TI (in one report by as much as 2.9 times). To obtain meaningful results, it is necessary to map the temperature elevation in 2-D (or 3-D) space. We present methodology, results and validation of a 2-D spatial and temporal thermal strain ultrasound temperature estimation technique in phantoms, and its apparently novel application in tracking the evolution of heat deposition at diagnostic exposure levels. The same ultrasound probe is used for both transmission and reception. The displacement and thermal strain estimation methods are similar to those used in high-intensity focused ultrasound thermal monitoring. The use of radiofrequency signals permits the application of cross correlation as a similarity measurement for tracking feature displacement. The displacement is used to calculate the thermal strain directly related to the temperature rise. Good agreement was observed between the temperature rise and the ultrasound power and scan duration. Thermal strain up to 1.4% was observed during 4000-s scan. Based on the results obtained for the temperature range studied in this work, the technique demonstrates potential for applicability in phantom (and possibly in vivo tissue

  4. Conserved B-cell epitopes among human bocavirus species indicate potential diagnostic targets.

    Directory of Open Access Journals (Sweden)

    Zhuo Zhou

    Full Text Available BACKGROUND: Human bocavirus species 1-4 (HBoV1-4 have been associated with respiratory and enteric infections in children. However, the immunological mechanisms in response to HBoV infections are not fully understood. Though previous studies have shown cross-reactivities between HBoV species, the epitopes responsible for this phenomenon remain unknown. In this study, we used genomic and immunologic approaches to identify the reactive epitopes conserved across multiple HBoV species and explored their potential as the basis of a novel diagnostic test for HBoVs. METHODOLOGY/PRINCIPAL FINDINGS: We generated HBoV1-3 VP2 gene fragment phage display libraries (GFPDLs and used these libraries to analyze mouse antisera against VP2 protein of HBoV1, 2, and 3, and human sera positive for HBoVs. Using this approach, we mapped four epitope clusters of HBoVs and identified two immunodominant peptides--P1 (¹MSDTDIQDQQPDTVDAPQNT²⁰, and P2 (¹⁶²EHAYPNASHPWDEDVMPDL¹⁸⁰--that are conserved among HBoV1-4. To confirm epitope immunogenicity, we immunized mice with the immunodominant P1 and P2 peptides identified in our screen and found that they elicited high titer antibodies in mice. These two antibodies could only recognize the VP2 of HBoV 1-4 in Western blot assays, rather than those of the two other parvoviruses human parvovirus B19 and human parvovirus 4 (PARV4. Based on our findings, we evaluated epitope-based peptide-IgM ELISAs as potential diagnostic tools for HBoVs IgM antibodies. We found that the P1+P2-IgM ELISA showed a higher sensitivity and specificity in HBoVs IgM detection than the assays using a single peptide. CONCLUSIONS/SIGNIFICANCE: The identification of the conserved B-cell epitopes among human bocavirus species contributes to our understanding of immunological cross-reactivities of HBoVs, and provides important insights for the development of HBoV diagnostic tools.

  5. Reverse iontophoresis of urea in health and chronic kidney disease: a potential diagnostic and monitoring tool?

    Science.gov (United States)

    Ebah, Leonard M; Read, Ian; Sayce, Andrew; Morgan, Jane; Chaloner, Christopher; Brenchley, Paul; Mitra, Sandip

    2012-01-01

    Background Patients with chronic kidney disease (CKD) need regular monitoring, usually by blood urea and creatinine measurements, needing venepuncture, frequent attendances and a healthcare professional, with significant inconvenience. Noninvasive monitoring will potentially simplify and improve monitoring. We tested the potential of transdermal reverse iontophoresis of urea in patients with CKD and healthy controls. Methods Using a MIC 2® Iontophoresis Controller, reverse iontophoresis was applied on the forearm of five healthy subjects (controls) and 18 patients with CKD for 3–5 h. Urea extracted at the cathode was measured and compared with plasma urea. Results Reverse iontophoresis at 250 μA was entirely safe for the duration. Cathodal buffer urea linearly correlated with plasma urea after 2 h (r = 0·82, P urea (y) from cathodal urea after 2 and 3 h, respectively. Cathodal urea concentration in controls was significantly lower than in patients with CKD after a minimum current application of 2 h (P urea cut-off of 30 μM gave a sensitivity of 83·3% and positive predictive value of 87% CKD. During haemodialysis, the fall in cathodal urea was able to track that of blood urea. Conclusion Reverse iontophoresis is safe, can potentially discriminate patients with CKD and healthy subjects and is able to track blood urea changes on dialysis. Further development of the technology for routine use can lead to an exciting opportunity for its use in diagnostics and monitoring. PMID:22409780

  6. The effect of glycosylation on the transferrin structure: A molecular dynamic simulation analysis.

    Science.gov (United States)

    Ghanbari, Z; Housaindokht, M R; Bozorgmehr, M R; Izadyar, M

    2016-09-07

    Transferrins have been defined by the highly cooperative binding of iron and a carbonate anion to form a Fe-CO3-Tf ternary complex. As such, the layout of the binding site residues affects transferrin function significantly; In contrast to N-lobe, C-lobe binding site of the transferrin structure has been less characterized and little research which surveyed the interaction of carbonate with transferrin in the C-lobe binding site has been found. In the present work, molecular dynamic simulation was employed to gain access into the molecular level understanding of carbonate binding site and their interactions in each lobe. Residues responsible for carbonate binding of transferrin structure were pointed out. In addition, native human transferrin is a glycoprotein that two N-linked complex glycan chains located in the C-lobe. Usually, in the molecular dynamic simulation for simplifying, glycan is removed from the protein structure. Here, we explore the effect of glycosylation on the transferrin structure. Glycosylation appears to have an effect on the layout of the binding site residue and transferrin structure. On the other hand, sometimes the entire transferrin formed by separated lobes that it allows the results to be interpreted in a straightforward manner rather than more parameters required for full length protein. But, it should be noted that there are differences between the separated lobe and full length transferrin, hence, a comparative analysis by the molecular dynamic simulation was performed to investigate such structural variations. Results revealed that separation in C-lobe caused a significant structural variation in comparison to N-lobe. Consequently, the separated lobes and the full length one are different, showing the importance of the interlobe communication and the impact of the lobes on each other in the transferrin structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Effects of transferrin on aromatase activity in porcine granulosa cells in vitro.

    Directory of Open Access Journals (Sweden)

    Małgorzata Duda

    2009-01-01

    Full Text Available Proliferating cells have an absolute requirement for iron, which is delivered by transferrin with subsequent intracellular transport via the transferrin receptor. Recent studies have reported that transferrin plays a crucial role in the local regulation of ovarian function, apart from its iron-binding characteristic. Therefore, the present study was undertaken to explore the possible role of transferrin in porcine granulosa cells function by examining its influence on aromatase activity, the most important indicator of follicular cell differentiation. In the first series of studies, pig granulosa cells isolated from small, immature follicles were cultured in the presence of transferrin alone (10 microg/ml or 100 microg/ml or with the addition of FSH (100ng/ml. The second series of studies was undertaken to determine transferrin-stimulated granulosa cells ability to aromatize exogenous testosterone (1x10(-7M. One hour after the establishment of cultures an aromatase inhibitor CGS16949A was added to test its influence on estradiol production. After 48 hours, cultures were terminated and cells were processed for immunocytochemical staining of aromatase. Media were frozen for further estradiol level analysis. Positive immunostaining for aromatase was found in all granulosa cell cultures. The intensity of immunostaining was always stronger in cultures supplemented with FSH whereas the addition of transferrin had no effect. Granulosa cells in vitro synthesized the highest amount of estradiol after the addition of FSH and exogenous testosterone as measured radioimmunologically. Concomitant treatment with FSH and transferrin caused an inhibition of FSH-stimulated aromatase activity. The production of estradiol also declined in the presence of FSH, testosterone and transferrin. This study demonstrates that transferrin had a dose-dependent inhibitory effect on FSH-stimulated aromatase activity, which was confirmed by radioimmunoassay. Our results indicate

  8. Does Preoperative Antimicrobial Prophylaxis Influence the Diagnostic Potential of Periprosthetic Tissues in Hip or Knee Infections?

    Science.gov (United States)

    Bedenčič, Klemen; Kavčič, Martina; Faganeli, Nataša; Mihalič, Rene; Mavčič, Blaž; Dolenc, Jožica; Bajc, Zlatka; Trebše, Rihard

    2016-01-01

    .40-2.48; p = 0.99). All measured tissue concentrations of cefazolin were greater than the minimum inhibitory concentration, therefore we found that antibiotic prophylaxis was adequate at the time of second-set tissue specimen recovery. Results from this small, prospective series suggest that preoperative antimicrobial prophylaxis may be administered safely even in patients undergoing revision hip or knee arthroplasty in which microbiologic sampling is planned without compromising the diagnostic sensitivity of tissue sample cultures. However, before applying our results more generally, our findings need to be confirmed in larger, multicenter studies that would allow evaluation by sex, procedure, bacteriology, and other potentially important factors. Level I, diagnostic study.

  9. Diagnostic potential of iris cross-sectional imaging in albinism using optical coherence tomography.

    Science.gov (United States)

    Sheth, Viral; Gottlob, Irene; Mohammad, Sarim; McLean, Rebecca J; Maconachie, Gail D E; Kumar, Anil; Degg, Christopher; Proudlock, Frank A

    2013-10-01

    To characterize in vivo anatomic abnormalities of the iris in albinism compared with healthy controls using anterior segment optical coherence tomography (AS-OCT) and to explore the diagnostic potential of this technique for albinism. We also investigated the relationship between iris abnormalities and other phenotypical features of albinism. Prospective cross-sectional study. A total of 55 individuals with albinism and 45 healthy controls. We acquired 4.37×4.37-mm volumetric scans (743 A-scans, 50 B-scans) of the nasal and temporal iris in both eyes using AS-OCT (3-μm axial resolution). Iris layers were segmented and thicknesses were measured using ImageJ software. Iris transillumination grading was graded using Summers and colleagues' classification. Retinal OCT, eye movement recordings, best-corrected visual acuity (BCVA), visual evoked potential (VEP), and grading of skin and hair pigmentation were used to quantify other phenotypical features associated with albinism. Iris AS-OCT measurements included (1) total iris thickness, (2) stroma/anterior border (SAB) layer thickness, and (3) posterior epithelial layer (PEL) thickness. Correlation with other phenotypical measurements, including (1) iris transillumination grading, (2) retinal layer measurements at the fovea, (3) nystagmus intensity, (4) BCVA, (5) VEP asymmetry, (6) skin pigmentation, and (7) hair pigmentation (of head hair, lashes, and brows). The mean iris thickness was 10.7% thicker in controls (379.3 ± 44.0 μm) compared with the albinism group (342.5 ± 52.6 μm; P>0.001), SAB layers were 5.8% thicker in controls (315.1 ± 43.8 μm) compared with the albinism group (297.7 ± 50.0 μm; P=0.044), and PEL was 44.0% thicker in controls (64.1 ± 11.7 μm) compared with the albinism group (44.5 ± 13.9 μm; Palbinism. Phenotypic features of albinism, such as skin and hair pigmentation, BCVA, and nystagmus intensity, were significantly correlated to AS-OCT iris thickness measurements. We have

  10. Solar wind and magnetosphere plasma diagnostics by spacecraft electrostatic potential measurements

    Directory of Open Access Journals (Sweden)

    A. Pedersen

    1995-02-01

    Full Text Available Several satellites (GEOS-1, GEOS-2, ISEE-1, Viking and CRRES carried electric field experiments on which probes were driven by a current from the satellite to be close to the plasma potential. The potential difference between an electric field probe and its spacecraft (with conductive surfaces can be used to determine the ambient electron density and/or electron flux with limited accuracy but with high time resolution, of the order of 10-100 ms. It is necessary for the development of this diagnostic method to understand the photoemission characteristics of probes and satellites. According to the electric field experiments on the above-mentioned satellites, all materials develop very similar photoemission properties when they are beyond the influence of atmospheric oxygen. The photoelectron yield steadily increases over the first few months in space and reaches values well above those measured on clean surfaces in the laboratory. The method can be used for solar radiation levels corresponding to distances from 0.4 to 5 AU from the Sun.

  11. ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool.

    Science.gov (United States)

    Weissenberger, S; Klicperova-Baker, M; Zimbardo, P; Schonova, K; Akotia, D; Kostal, J; Goetz, M; Raboch, J; Ptacek, R

    2016-01-01

    The article draws primarily from the behavioral findings (mainly psychiatric and psychological observations) and points out the important relationships between attention-deficit/hyperactivity disorder (ADHD) symptoms and time orientation. Specifically, the authors argue that there is a significant overlap between the symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo's time perspective theory and assessed by Zimbardo Time Perspective Inventory. Developmental data on Present Hedonism of males and females in the Czech population sample (N=2201) are also presented. The hypothesis of relationship between ADHD and Present Hedonism is mainly derived from the prevalence of addictive behavior (mainly excessive Internet use, alcohol abuse, craving for sweets, fatty foods, and fast foods), deficits in social learning, and increased aggressiveness both in ADHD and in the population scoring high on Present Hedonism in the Zimbardo Time Perspective Inventory. We conclude that Zimbardo's time perspective offers both: 1) a potential diagnostic tool - the Zimbardo Time Perspective Inventory, particularly its Present Hedonism scale, and 2) a promising preventive and/or therapeutic approach by the Time Perspective Therapy. Time Perspective Therapy has so far been used mainly to treat past negative trauma (most notably, posttraumatic stress disorder); however, it also has value as a potential therapeutic tool for possible behavioral compensation of ADHD.

  12. Transferrin variation and evolution of Canadian barren-ground caribou

    Directory of Open Access Journals (Sweden)

    Knut H. Røed

    1990-09-01

    Full Text Available Blood samples were obtained from 95 barren-ground caribou (Rangifer tarandus groenlandicus of the Beverly herd in Northwest Territories, Canada. Polyacrylamid gel electrophoresis was used to score for genetic variation in the locus coding for transferrin. The pattern of allele frequency distribution are compared with previously reported values of Eurasian tundra reindeer (R.t. tarandus, Alaska caribou (R.t. granti, Peary caribou (R.t. pearyi, and Svalbard reindeer (R.t. platyrhynchus. In the Beverly herd a total of 21 different transferrin alleles were detected. The amount of genetic variation was higher in the Canadian barren-ground caribou than what has been detected in other subspecies of reindeer/caribou. Highly gene-tical differences in the allele frequencies were detected between the Canadian barren-ground caribou and the other subspecies. The genetic identity analyses indicates approximately the same amount of genetic differentiation when the Canadian barren-ground caribou are compared with Alaska caribou as with the Peary caribou. The allele frequency pattern could be explained by a possible origin of the Canadian barren-ground caribou from an ancestral population which was genetical influenced by animals surviving the We-ichselian glaciation in refugia both in high Arctic, in Beringia, and south of the ice sheet.

  13. Clinical usefulness of 111In transferrin scintigraphy in colorectal cancer

    International Nuclear Information System (INIS)

    Hirano, Morihisa; Naruki, Yukihiko; Urita, Yosihisa; Nakatani, Naoto; Otsuka, Sachio; Noguchi, Masahiro; Takano, Masaaki; Maruyama, Yuuzou.

    1993-01-01

    As assessment was made regarding the clinical value of 111 In transferrin in scintigraphy on 28 lesions in 26 cases of colorectal cancer. The positive rate of colorectal cancer was high: 21 lesions out of the 28 (75%) were found to be positive. As for the location of cancer, there was a tendency for the positive rate to be high in the ascending and transverse colon. There was no obvious trend regarding Borrmann's classification, histological type, or macroscopic depth of invasion. There was a trend for cases in which the maximum diameter of the tumor was large and depth of invasion was in progress to be positive. Ten cases in which a specimen was resected were all shown to be positive by scintigraphy. Radioactivity in the tumorous regions was 4.41±2.96 times that of the non-tumorous regions. Moreover, tumorous tissue was strongly stained by the immuno-histological staining with anti-Tf-receptor antibody. From the above findings, it was considered that 111 In transferrin is clinically useful in scintigraphy, since it is evident that it accumulates in the tissue of colorectal cancer. (author)

  14. BLOOD PROTEIN TRANSFERRIN POLYMOROPHISM IN BLACK BENGAL GOAT

    Directory of Open Access Journals (Sweden)

    Rajesh Paul

    2017-12-01

    Full Text Available The present investigation was carried out with an aim to explore the polymorphism of a blood protein tranferrin using starch gel electrophoresis technique in a total of unrelated 199 Black Bengal goats available in four different districts of West Bengal, India. Banding patterns of transferrin in starch gel revealed six phenovariants TfAA, TfAB, TfBC, TfBB, TfAC and TfCC comprising of three allelomorphs, TfA, TfB and TfC. The genotype frequencies were found to be observed 0.211, 0.347, 0.136, 0.106, 0.136 and 0.065 for six genotypes and the allelic frequencies were 0.452, 0.347 and 0.201 for three alleles, respectively. Result of Chi-square test revealed that the population under study was in Hardy Weinberg Equilibrium. There were polymorphism in Transferrin protein and the presence of differences among the frequencies of the three alleles by categories could be a source of genetic variation in Black Bengal goat.

  15. Comparison of transferrin isoform analysis by capillary electrophoresis and HPLC for screening congenital disorders of glycosylation.

    Science.gov (United States)

    Dave, Mihika B; Dherai, Alpa J; Udani, Vrajesh P; Hegde, Anaita U; Desai, Neelu A; Ashavaid, Tester F

    2018-01-01

    Transferrin, a major glycoprotein has different isoforms depending on the number of sialic acid residues present on its oligosaccharide chain. Genetic variants of transferrin as well as the primary (CDG) & secondary glycosylation defects lead to an altered transferrin pattern. Isoform analysis methods are based on charge/mass variations. We aimed to compare the performance of commercially available capillary electrophoresis CDT kit for diagnosing congenital disorders of glycosylation with our in-house optimized HPLC method for transferrin isoform analysis. The isoform pattern of 30 healthy controls & 50 CDG-suspected patients was determined by CE using a Carbohydrate-Deficient Transferrin kit. The results were compared with in-house HPLC-based assay for transferrin isoforms. Transferrin isoform pattern for healthy individuals showed a predominant tetrasialo transferrin fraction followed by pentasialo, trisialo, and disialotransferrin. Two of 50 CDG-suspected patients showed the presence of asialylated isoforms. The results were comparable with isoform pattern obtained by HPLC. The commercial controls showed a <20% CV for each isoform. Bland Altman plot showed the difference plot to be within +1.96 with no systemic bias in the test results by HPLC & CE. The CE method is rapid, reproducible and comparable with HPLC and can be used for screening Glycosylation defects. © 2017 Wiley Periodicals, Inc.

  16. Ionization-potential depression and other dense plasma statistical property studies - Application to spectroscopic diagnostics.

    Science.gov (United States)

    Calisti, Annette; Ferri, Sandrine; Mossé, Caroline; Talin, Bernard

    2017-02-01

    The radiative properties of an emitter surrounded by a plasma, are modified through various mechanisms. For instance the line shapes emitted by bound-bound transitions are broadened and carry useful information for plasma diagnostics. Depending on plasma conditions the electrons occupying the upper quantum levels of radiators no longer exist as they belong to the plasma free electron population. All the charges present in the radiator environment contribute to the lowering of the energy required to free an electron in the fundamental state. This mechanism is known as ionization potential depression (IPD). The knowledge of IPD is useful as it affects both the radiative properties of the various ionic states and their populations. Its evaluation deals with highly complex n-body coupled systems, involving particles with different dynamics and attractive ion-electron forces. A classical molecular dynamics (MD) code, the BinGo-TCP code, has been recently developed to simulate neutral multi-component (various charge state ions and electrons) plasma accounting for all the charge correlations. In the present work, results on IPD and other dense plasma statistical properties obtained using the BinGo-TCP code are presented. The study focuses on aluminum plasmas for different densities and several temperatures in order to explore different plasma coupling conditions.

  17. ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer.

    Science.gov (United States)

    Shi, Yanhua; Wang, Wei; Yang, Baozhi; Tian, Hongge

    2017-10-01

    Cervical cancer is one of the most common cancers among women worldwide. It is highly lethal yet can be treated when found in early stage. Thus, early detection is of significant important for early diagnosis of cervical cancer. Exosomes have been used as biomarkers in clinical diagnosis. It is unknown that whether blood exosomes associated with cervical cancer can be detected and if these exosomes can accurately represent the developmental stage of cervical cancer. Mouse models were made out of a relapsed cervical cancer patient's tumour sample for original and recurrent cervical cancer, and gene analysis in both tumours and exosomes in these mouse models were performed. We found that activating transcription factor 1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary and recurrent cervical cancer mouse model, and they can also be detected in the blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1 and RAS genes were found significantly elevated in tumours of primary and recurrent cervical cancer mouse model, and they were also detected in the blood exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for cervical cancer in the future. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Autoantibodies in a Three-Year-Old Girl with Visceral Leishmaniasis: A Potential Diagnostic Pitfall

    Directory of Open Access Journals (Sweden)

    Gholamreza Pouladfar

    2016-01-01

    Full Text Available Visceral leishmaniasis (VL, a life-threatening parasitic infection, is endemic in the Mediterranean region. Diagnosis of VL is based on epidemiologic, clinical, and laboratory findings. However, sometimes, clinical features and laboratory findings overlap with those of autoimmune diseases. In some cases, autoantibodies are detected in patients with VL and this could be a potential diagnostic pitfall. In this study, we have reported on a three-year-old girl from a VL-endemic area in Iran, who presented with prolonged fever and splenomegaly. Bone marrow examination, serologic tests, and the molecular PCR assay were performed; however, results were inconclusive. The levels of anti-double stranded DNA, cytoplasmic antineutrophil cytoplasmic autoantibody, and perinuclear antineutrophil cytoplasmic autoantibody were elevated and, at the end, splenic biopsy was performed. The splenic tissue PCR test detected the DNA of Leishmania infantum. The patient’s condition improved with anti-Leishmania therapy, and the autoantibodies disappeared within the following four months. Clinical presentations and laboratory findings of VL and autoimmune diseases may overlap in some patients.

  19. Folic acid modified gelatine coated quantum dots as potential reagents for in vitro cancer diagnostics

    LENUS (Irish Health Repository)

    Gerard, Valerie A

    2011-11-10

    Abstract Background Gelatine coating was previously shown to effectively reduce the cytotoxicity of CdTe Quantum Dots (QDs) which was a first step towards utilising them for biomedical applications. To be useful they also need to be target-specific which can be achieved by conjugating them with Folic Acid (FA). Results The modification of QDs with FA via an original "one-pot" synthetic route was proved successful by a range of characterisation techniques including UV-visible absorption spectroscopy, Photoluminescence (PL) emission spectroscopy, fluorescence life-time measurements, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The resulting nanocomposites were tested in Caco-2 cell cultures which over-express FA receptors. The presence of FA on the surface of QDs significantly improved the uptake by targeted cells. Conclusions The modification with folic acid enabled to achieve a significant cellular uptake and cytotoxicity towards a selected cancer cell lines (Caco-2) of gelatine-coated TGA-CdTe quantum dots, which demonstrated good potential for in vitro cancer diagnostics.

  20. Transformation of vibration signals in rotary blood pumps: the diagnostic potential of pump failure.

    Science.gov (United States)

    Kawahito, Koji

    2013-09-01

    Although non-destructive and continuous monitoring is indispensable for long-term circulatory support with rotary blood pumps, a practical monitoring system has not yet been developed. The objective of this study was to investigate the possibility of detecting pump failure caused by thrombus formation through the monitoring of vibration signals. The data acquisition equipment included vibration pickups, a charge amplifier, vibration analysis systems, and exclusive hardware. A pivot-bearing centrifugal pump with a mock circuit was investigated for vibration analysis. To simulate the four common areas of thrombus formation, we used a piece of silicon attached to each of the following four locations: the total area of the bottom of the impeller, an eccentric shape on the bottom of the impeller, a circular shape around the shaft top, and an eccentric shape on the top of the impeller. Vibration signals were picked up, and the power spectrum density analysis was performed at pump rotational speeds of 2100, 2400, and 3000 rpm. In this study, pump failure could be detected, and the types of imitation thrombi could be determined. We conclude that vibration detection with a computerized analysis system is a potentially valuable diagnostic tool for long-term circulatory support with rotary blood pumps.

  1. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Ming-Ming Tsai

    2016-06-01

    Full Text Available Human gastric cancer (GC is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

  2. ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool

    Directory of Open Access Journals (Sweden)

    Weissenberger S

    2016-11-01

    Full Text Available S Weissenberger,1 M Klicperova-Baker,2 P Zimbardo,3 K Schonova,1 D Akotia,1 J Kostal,2 M Goetz,4 J Raboch,1 R Ptacek1 1First Medical Faculty, Charles University, 2Institute of Psychology, Academy of Sciences of the Czech Republic, Praha, Czech Republic; 3Department of Psychology, Stanford University, Stanford, CA, USA; 4Second Faculty of Medicine, Department of Child Psychiatry, Charles University, Motol University Hospital, Praha, Czech RepublicAbstract: The article draws primarily from the behavioral findings (mainly psychiatric and psychological observations and points out the important relationships between attention-deficit/hyperactivity disorder (ADHD symptoms and time orientation. Specifically, the authors argue that there is a significant overlap between the symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo’s time perspective theory and assessed by Zimbardo Time Perspective Inventory. Developmental data on Present Hedonism of males and females in the Czech population sample (N=2201 are also presented. The hypothesis of relationship between ADHD and Present Hedonism is mainly derived from the prevalence of addictive behavior (mainly excessive Internet use, alcohol abuse, craving for sweets, fatty foods, and fast foods, deficits in social learning, and increased aggressiveness both in ADHD and in the population high on Present Hedonism. We conclude that Zimbardo’s time perspective offers both: 1 a potential diagnostic tool – the Zimbardo Time Perspective Inventory, particularly its Present Hedonism scale, and 2 a promising preventive and/or therapeutic approach by the Time Perspective Therapy. Time Perspective Therapy has so far been used mainly to treat past negative trauma (most notably, posttraumatic stress disorder; however, it also has value as a potential therapeutic tool for possible behavioral compensation of ADHD.Keywords: ADHD, time perspective, ZTPI, Zimbardo, addiction, alcoholism, delinquency

  3. Wide-field lifetime-based FRET imaging for the assessment of early functional distribution of transferrin-based delivery in breast tumor-bearing small animals

    Science.gov (United States)

    Sinsuebphon, Nattawut; Rudkouskaya, Alena; Barroso, Margarida; Intes, Xavier

    2016-02-01

    Targeted drug delivery is a critical aspect of successful cancer therapy. Assessment of dynamic distribution of the drug provides relative concentration and bioavailability at the target tissue. The most common approach of the assessment is intensity-based imaging, which only provides information about anatomical distribution. Observation of biomolecular interactions can be performed using Förster resonance energy transfer (FRET). Thus, FRET-based imaging can assess functional distribution and provide potential therapeutic outcomes. In this study, we used wide-field lifetime-based FRET imaging for the study of early functional distribution of transferrin delivery in breast cancer tumor models in small animals. Transferrin is a carrier for cancer drug delivery. Its interaction with its receptor is within a few nanometers, which is suitable for FRET. Alexa Fluor® 700 and Alexa Fluor® 750 were conjugated to holo-transferrin which were then administered via tail vein injection to the mice implanted with T47D breast cancer xenografts. Images were continuously acquired for 60 minutes post-injection. The results showed that transferrin was primarily distributed to the liver, the urinary bladder, and the tumor. The cellular uptake of transferrin, which was indicated by the level of FRET, was high in the liver but very low in the urinary bladder. The results also suggested that the fluorescence intensity and FRET signals were independent. The liver showed increasing intensity and increasing FRET during the observation period, while the urinary bladder showed increasing intensity but minimal FRET. Tumors gave varied results corresponding to their FRET progression. These results were relevant to the biomolecular events that occurred in the animals.

  4. Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease.

    Directory of Open Access Journals (Sweden)

    Shivali Gupta

    Full Text Available Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and an emerging infectious disease in the US and Europe. We have shown TcG1, TcG2, and TcG4 antigens elicit protective immunity to T. cruzi in mice and dogs. Herein, we investigated antigenicity of the recombinant proteins in humans to determine their potential utility for the development of next generation diagnostics for screening of T. cruzi infection and Chagas disease.Sera samples from inhabitants of the endemic areas of Argentina-Bolivia and Mexico-Guatemala were analyzed in 1(st-phase for anti-T. cruzi antibody response by traditional serology tests; and in 2(nd-phase for antibody response to the recombinant antigens (individually or mixed by an ELISA. We noted similar antibody response to candidate antigens in sera samples from inhabitants of Argentina and Mexico (n=175. The IgG antibodies to TcG1, TcG2, and TcG4 (individually and TcG(mix were present in 62-71%, 65-78% and 72-82%, and 89-93% of the subjects, respectively, identified to be seropositive by traditional serology. Recombinant TcG1- (93.6%, TcG2- (96%, TcG4- (94.6% and TcG(mix- (98% based ELISA exhibited significantly higher specificity compared to that noted for T. cruzi trypomastigote-based ELISA (77.8% in diagnosing T. cruzi-infection and avoiding cross-reactivity to Leishmania spp. No significant correlation was noted in the sera levels of antibody response and clinical severity of Chagas disease in seropositive subjects.Three candidate antigens were recognized by antibody response in chagasic patients from two distinct study sites and expressed in diverse strains of the circulating parasites. A multiplex ELISA detecting antibody response to three antigens was highly sensitive and specific in diagnosing T. cruzi infection in humans, suggesting that a diagnostic kit based on TcG1, TcG2 and TcG4 recombinant proteins will be useful in diverse situations.

  5. Complex formation of transferrin with tetravalent plutonium and cerium

    International Nuclear Information System (INIS)

    Subramanian, M.S.; Oomen, I.K.

    1981-01-01

    Gel filtration experiments with 239 Pu labelled In Vitro bovine serum showed that the metal ion is bound to the transferrin of the serum proteins as in the case of iron labelled serum. This was confirmed by polyacrylamide gel electrophoresis. The ovotransferrin prepared from chicken egg white which was devoid of hemopexin contaminant was found to complex both tetravalent plutonium and cerium giving visible absorption peak at 365 and 435 nm respectively. The binding capacity of ovotransferrin with tetravalent plutonium and cerium, determined by spectrophotometric titration indicates that two metal ions are bound to each protein molecule as in the case of iron. The average molecular weight computed from this binding capacity measurements was found to be 71,000-75,000. The number of protons liberated for each metal ion bound was found to be three as in the case of iron. (author)

  6. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart

    Directory of Open Access Journals (Sweden)

    Wenjing Xu

    2015-10-01

    Full Text Available Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1 might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure.

  7. TTP specifically regulates the internalization of the transferrin receptor

    DEFF Research Database (Denmark)

    Tosoni, Daniela; Puri, Claudia; Confalonieri, Stefano

    2005-01-01

    Different plasma membrane receptors are internalized through saturable/noncompetitive pathways, suggesting cargo-specific regulation. Here, we report that TTP (SH3BP4), a SH3-containing protein, specifically regulates the internalization of the transferrin receptor (TfR). TTP interacts...... with endocytic proteins, including clathrin, dynamin, and the TfR, and localizes selectively to TfR-containing coated-pits (CCP) and -vesicles (CCV). Overexpression of TTP specifically inhibits TfR internalization, and causes the formation of morphologically aberrant CCP, which are probably fission impaired....... This effect is mediated by the SH3 of TTP, which can bind to dynamin, and it is rescued by overexpression of dynamin. Functional ablation of TTP causes a reduction in TfR internalization, and reduced cargo loading and size of TfR-CCV. Tyrosine phosphorylation of either TTP or dynamin prevents...

  8. The Confidence-Accuracy Relationship in Diagnostic Assessment: The Case of the Potential Difference in Parallel Electric Circuits

    Science.gov (United States)

    Saglam, Murat

    2015-01-01

    This study explored the relationship between accuracy of and confidence in performance of 114 prospective primary school teachers in answering diagnostic questions on potential difference in parallel electric circuits. The participants were required to indicate their confidence in their answers for each question. Bias and calibration indices were…

  9. Evidence that transferrin supports cell proliferation by supplying iron for DNA synthesis

    International Nuclear Information System (INIS)

    Laskey, J.; Webb, I.; Schulman, H.M.; Ponka, P.

    1988-01-01

    Transferrin is essential for cell proliferation and it was suggested that it may trigger a proliferative response following its interaction with receptors, serving as a growth factor. However, since the only clearly defined function of transferrin is iron transport, it may merely serve as an iron donor. To further clarify this issue, the authors took advantage of an iron chelate, ferric salicylaldehyde isonicotinoyl hydrazone (Fe-SIH), which they developed and previously demonstrated to efficiently supply iron to cells without using physiological transferrin receptor pathway. As expected, they observed that blocking monoclonal antibodies against transferrin receptors inhibited proliferation of both Raji and murine erythroleukemia cells. This inhibited cell growth was rescued upon the addition of Fe-SIH which was also shown to deliver iron to Raji cells in the presence of blocking anti-transferrin receptor antibodies. Moreover, blocking anti-transferrin receptor antibodies inhibited [ 3 H]thymidine incorporation into DNA and this inhibition could be overcome by added Fe-SIH. In addition, Fe-SIH slightly stimulated, while SIH (an iron chelator) significantly inhibited, DNA synthesis in phytohemagglutinin-stimulated peripheral blood lymphocytes. Taken together, these results indicate that the only function of transferrin supporting cell proliferation is to supply cells with iron

  10. Comparison of Different Matrices as Potential Quality Control Samples for Neurochemical Dementia Diagnostics

    NARCIS (Netherlands)

    Lelental, Natalia; Brandner, Sebastian; Kofanova, Olga; Blennow, Kaj; Zetterberg, Henrik; Andreasson, Ulf; Engelborghs, Sebastiaan; Mroczko, Barbara; Gabryelewicz, Tomasz; Teunissen, Charlotte; Mollenhauer, Brit; Parnetti, Lucilla; Chiasserini, Davide; Molinuevo, Jose Luis; Perret-Liaudet, Armand; Verbeek, Marcel M.; Andreasen, Niels; Brosseron, Frederic; Bahl, Justyna M. C.; Herukka, Sanna-Kaisa; Hausner, Lucrezia; Froelich, Lutz; Labonte, Anne; Poirier, Judes; Miller, Anne-Marie; Zilka, Norbert; Kovacech, Branislav; Urbani, Andrea; Suardi, Silvia; Oliveira, Catarina; Baldeiras, Ines; Dubois, Bruno; Rot, Uros; Lehmann, Sylvain; Skinningsrud, Anders; Betsou, Fay; Wiltfang, Jens; Gkatzima, Olymbia; Winblad, Bengt; Buchfelder, Michael; Kornhuber, Johannes; Lewczuk, Piotr

    2016-01-01

    Background: Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples.

  11. The diagnostic potential of salivary protease activities in periodontal health and disease

    NARCIS (Netherlands)

    Thomadaki, K.; Bosch, J.A.; Oppenheim, F.G.; Helmerhorst, E.J.

    2013-01-01

    Periodontal disease is characterised by proteolytic processes involving enzymes that are released by host immune cells and periodontal bacteria. These enzymes, when detectable in whole saliva, may serve as valuable diagnostic markers for disease states and progression. Because the substrate

  12. PAX8 Expression in Solitary Fibrous Tumor: A Potential Diagnostic Pitfall.

    Science.gov (United States)

    Ullman, David; Gordetsky, Jennifer; Siegal, Gene P; Prieto-Granada, Carlos N; Wei, Shi; Stevens, Todd M

    2017-07-26

    PAX8 is used as a diagnostic aid in classifying retroperitoneal (RP) spindle cell tumors. PAX8 positivity in a spindled RP tumor is typically associated with sarcomatoid renal cell carcinoma (SRCC). However, PAX8 expression in solitary fibrous tumor (SFT), a tumor not uncommon to the RP, has not been extensively studied. We investigated the expression of PAX8 in SFTs and other spindle cell RP tumors. We collected 30 SFT, 23 SRCC, 11 gastrointestinal stromal tumors, 2 synovial sarcomas, 6 dedifferentiated liposarcomas (DDLS), 4 well differentiated liposarcomas (WDLS), and select other tumors. We identified nuclear PAX8 expression in 13 of 30 (43%) SFT, 0 of 6 (0%) DDLS, and 1 of 4 (25%) WDLS. Twenty-eight of 30 (93%) SFT, 0 of 23 (0%) SRCC, 2 of 6 (33%) DDLS, and 1 of 4 (25%) WDLS showed nuclear STAT6 expression. All gastrointestinal stromal tumors were negative for both PAX8 and STAT6. Of the 13 SFT showing PAX8 expression, 8 showed diffuse expression and 5 expressed PAX8 focally. Extrapleural SFTs were more likely to express PAX8 compared with pleural SFTs (10/13; 77% vs. 3/17; 18%, respectively; P=0.00117). Twenty of 23 (87%) SRCC expressed PAX8; the sarcomatoid component of all 23 SRCC was negative for STAT6. Of the other spindle cell tumors studied, 1 of 2 synovial sarcomas and 1 of 2 histiocytic sarcomas showed PAX8 expression. Pathologists should be aware of the potential pitfall of the relatively frequent expression of PAX8 by SFT and STAT6 expression in liposarcoma. PAX8 expression by a spindle cell lesion of RP would not allow distinction between SFT, SRCC, or sclerosing liposarcoma by itself. A STAT6/PAX8 phenotype excludes SRCC.

  13. Diagnostic potential of low molecular weight excretory secretory proteins of Paramphistomum epiclitum for caprine amphistomosis.

    Science.gov (United States)

    Jaiswal, Amit Kumar; Shanker, Daya; Sudan, Vikrant; Singh, Amit

    2018-06-15

    In the present study, the 75% alcoholic fractionation of excretory-secretory (ES) antigen isolated from 200 to 300 live P. epiclitum was assessed for its diagnostic potential for the detection of caprine amphistomosis by using antibody detection enzyme immunoassay. Prior to enzyme immunoassay, 75% alcoholic fractionation of excretory-secretory (ES) antigen was subjected to SDS- PAGE and western blot analysis for the presence of immunoreactive polypeptides. SDS-PAGE analysis of ES antigen resolved a total 7 polypeptides bands of size 56, 27, 25, 22.5, 12, 11 and 10 kDa. Western blot analysis revealed only two immunoreactive polypeptides (11 kDa and 12 kDa) when polypeptides resolved in SDS-PAGE were probed with known positive pooled serum. None of the polypeptides showed reactions with pooled known negative serum. The working dilutions of antigen, sera and conjugates were determined by checkerboard titration for employing ELISA and cut-off O.D. was calculated 0.616 by using the mean absorbance value of 11 negative kid sera. The sensitivity and specificity of ELISA was found to be 100% and 86.76%, respectively. As per kappa value estimation, the strength of agreement was found to be good. Antibodies to 75% alcoholic fractionation of ES antigen was detected in 20% goats (n = 160) of either sex, although faecal examination detected 10.6% goats to be infected with amphistomosis. The study confirmed that 75% alcoholic fractionation of ES antigen of P. epiclitum based ELISA had good value for serodiagnosis of caprine amphistomosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Soft-tissue inflammatory myofibroblastic tumors (IMTs) of the limbs: potential and limits of diagnostic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Masciocchi, Carlo; Lanni, Giuseppe; Conti, Laura; Conchiglia, Armando; Fascetti, Eva; Barile, Antonio [University of L' Aquila, S. Salvatore Hospital, Department of Radiology, Coppito, L' Aquila (Italy); Flamini, Stefano [S. Salvatore Hospital, Department of Orthopaedic Surgery, Coppito, L' Aquila (Italy); Coletti, Gino [S. Salvatore Hospital, Department of Pathology, Coppito, L' Aquila (Italy)

    2012-06-15

    The objective of this work was to evaluate the potential of diagnostic imaging in the identification, localization, and characterization of soft-tissue inflammatory myofibroblastic tumors (IMTs) of limbs with correlation to differential diagnosis and therapy. From a retrospective analysis of 324 histologically verified soft-tissue lesions of limbs and extremities diagnosed in our institute from January 2002 to July 2010, we selected seven cases of histologically proven IMT. These included six males and one female, aged between 28 and 81 years (mean age, 57 years). Lesions were localized in three cases to the thigh, in two cases to the popliteal space, and in the remaining two cases, to the shoulder girdle. All patients were evaluated on the basis of US, CT, and MRI. Ultrasound detected the presence of a non-homogeneous solid formation in all cases and calcifications in three cases. CT showed the presence and type of calcification/ossification and bone reaction. On MRI, all cases had low signal intensity on SE T1-weighted sequences and an intermediate-low signal intensity on SE and FSE T2-weighted sequences in six of them; only one case had an intermediate-high signal intensity on SE and FSE T2-weighted sequences. Both contrast-enhanced CT and MRI showed precocious enhancement in association with multiple peripheral hypertrophic blood vessels. On the basis of integrated imaging data obtained by US, CT, and MRI, it is possible to evaluate the lesion extension to provide a loco-regional staging, to characterize IMTs, and to allow an optimal therapeutical planning. (orig.)

  15. Ultrasensitive Sensing Material Based on Opal Photonic Crystal for Label-Free Monitoring of Transferrin.

    Science.gov (United States)

    Wu, Enqi; Peng, Yuan; Zhang, Xihao; Bai, Jialei; Song, Yanqiu; He, Houluo; Fan, Longxing; Qu, Xiaochen; Gao, Zhixian; Liu, Ying; Ning, Baoan

    2017-02-22

    A new opal photonic crystal (PC) sensing material, allowing label-free detection of transferrin (TRF), is proposed in the current study. This photonic crystal was prepared via a vertical convective self-assembly method with monodisperse microspheres polymerized by methyl methacrylate (MMA) and 3-acrylamidophenylboronic acid (AAPBA). FTIR, TG, and DLS were used to characterize the components and particle size of the monodisperse microspheres. SEM was used to observe the morphology of the PC. The diffraction peak intensity decreases as the TRF concentration increase. This was due to the combination of TRF to the boronic acid group of the photonic crystal. After condition optimization, a standard curve was obtained and the linear range of TRF concentration was from 2 × 10 -3 ng/mL to 200 ng/mL. Measurement of TRF concentration in simulated urine sample was also investigated using the sensing material. The results indicated that the PC provided a cheap, label-free, and easy-to-use alternative for TRF determination in clinical diagnostics.

  16. Iron status of Filipino infants and preschoolers using plasma ferritin and transferrin receptor levels.

    Science.gov (United States)

    Kuizon, M D; Madriaga, J R; Desnacido, J A; Cheong, R L; Perlas, L A

    1996-06-01

    Iron status of 1,861 Filipino infants and preschoolers was evaluated by measurements of plasma ferritin (PF), transferrin receptor (TR) and hemoglobin (Hb). One group of subjects (Group I) consisted of all anemic subjects together with a systematic subsample from the Fourth National Nutrition Survey-Biochemical Phase. Results showed that depleted iron stores based on PF ( 8.5 mg/l) was present in higher proportion (80.0% and 73.7% for infants and preschoolers) which was comparable to the proportion of anemia (80.3%). In a subgroup of subjects from the Country Program for Children IV (Group 2) elevated TR was present in 61.4% of infants and 46.5% of preschoolers. A lower proportion of depleted iron stores of 22.7% in infants and 15.2% in preschoolers was observed. Correlation test showed that there was a closer relationship between Hb and TR (r = -0.42) than Hb and PF (r = 0.20) even if PF was expected to give a higher proportion of values below normal. The occurrence of anemia in the presence of elevated TR without any decrease in PF values suggest that the diagnostic ability of PF could be limited in the presence of infection. Therefore, future studies should include biochemical tests such as C-reactive proteins (CRP) to determine the extent of association between anemia and infection.

  17. Diagnostic Potential of Plasmatic MicroRNA Signatures in Stable and Unstable Angina

    Science.gov (United States)

    D'Alessandra, Yuri; Carena, Maria Cristina; Spazzafumo, Liana; Martinelli, Federico; Bassetti, Beatrice; Devanna, Paolo; Rubino, Mara; Marenzi, Giancarlo; Colombo, Gualtiero I.; Achilli, Felice; Maggiolini, Stefano; Capogrossi, Maurizio C.; Pompilio, Giulio

    2013-01-01

    Purpose We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina. Methods An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated. Results Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA. Conclusions This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients. PMID:24260372

  18. Potential biomarker panels in overall breast cancer management: advancements by multilevel diagnostics.

    Science.gov (United States)

    Girotra, Shantanu; Yeghiazaryan, Kristina; Golubnitschaja, Olga

    2016-09-01

    Breast cancer (BC) prevalence has reached an epidemic scale with half a million deaths annually. Current deficits in BC management include predictive and preventive approaches, optimized screening programs, individualized patient profiling, highly sensitive detection technologies for more precise diagnostics and therapy monitoring, individualized prediction and effective treatment of BC metastatic disease. To advance BC management, paradigm shift from delayed to predictive, preventive and personalized medical services is essential. Corresponding step forwards requires innovative multilevel diagnostics procuring specific panels of validated biomarkers. Here, we discuss current instrumental advancements including genomics, proteomics, epigenetics, miRNA, metabolomics, circulating tumor cells and cancer stem cells with a focus on biomarker discovery and multilevel diagnostic panels. A list of the recommended biomarker candidates is provided.

  19. Screening of potential diagnostic markers and therapeutic targets against colorectal cancer

    Directory of Open Access Journals (Sweden)

    Tian XQ

    2015-07-01

    Full Text Available XiaoQing Tian, DanFeng Sun, ShuLiang Zhao, Hua Xiong, JingYuan Fang Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Objective: To identify genes with aberrant promoter methylation for developing novel diagnostic markers and therapeutic targets against primary colorectal cancer (CRC. Methods: Two paired CRC and adjacent normal tissues were collected from two CRC patients. A Resi: MBD2b protein-sepharose-4B column was used to enrich the methylated DNA fragments. Difference in the average methylation level of each DNA methylation region between the tumor and control samples was determined by log2 fold change (FC in each patient to screen the differentially methylated DNA regions. Genes with log2FC value ≥4 or ≤-4 were identified to be hypermethylated and hypomethylated, respectively. Then, the underlying functions of methylated genes were speculated by Gene Ontology database and pathway enrichment analyses. Furthermore, a protein–protein interaction network was built using Search Tool for the Retrieval of Interacting Genes/Proteins database, and the transcription factor binding sites were screened via the Encyclopedia of DNA Elements (ENCODE database. Results: Totally, 2,284 and 1,142 genes were predicted to have aberrant promoter hypermethylation or hypomethylation, respectively. MAP3K5, MAP3K8, MAPK14, and MAPK9 with promoter hypermethylation functioned via MAPK signaling pathway, focal adhesion, or Wnt signaling pathway, whereas MAP2K1, MAPK3, MAPK11, and MAPK7 with promoter hypomethylation functioned via TGF-beta signaling pathway, neurotrophin signaling pathway, and chemokine signaling pathway. CREBBP, PIK3R1, MAPK14, APP, ESR1, MAPK3, and HRAS were the seven hubs in the constructed protein–protein interaction network. RPL22, RPL36, RPLP2, RPS7, and RPS9 were commonly regulated by

  20. Diagnostic potential of recombinant scFv antibodies generated against hemagglutinin protein of influenza A virus

    Directory of Open Access Journals (Sweden)

    Roopali eRajput

    2015-09-01

    Full Text Available Human influenza A viruses have been the cause of enormous socio-economic losses worldwide. In order to combat such a notorious pathogen, hemagglutinin protein (HA has been a preferred target for generation of neutralizing-antibodies, as potent therapeutic/ diagnostic agents. In the present study, recombinant anti-HA single chain variable fragment (scFv antibodies were constructed using the phage display technology to aid in diagnosis and treatment of human influenza A virus infections. Spleen cells of mice hyper-immunized with A/New Caledonia/20/99 (H1N1 virus were used as the source for recombinant antibody (rAb production. The antigen-binding phages were quantified after 6 rounds of bio-panning against A/New Caledonia/20/99 (H1N1, A/California/07/2009 (H1N1-like, or A/Udorn/307/72(H3N2 viruses. The phage yield was maximum for the A/New Caledonia/20/99 (H1N1, however, considerable cross-reactivity was observed for the other virus strains as well. The HA-specific polyclonal rAb preparation was subjected to selection of single clones for identification of high reactive relatively conserved epitopes. The high affinity rAbs were tested against certain known conserved HA epitopes by peptide ELISA. Three recombinant mAbs showed reactivity with both the H1N1 strains and one (C5 showed binding with all the three viral strains. The C5 antibody was thus used for development of an ELISA test for diagnosis of influenza virus infection. Based on the sample size in the current analysis, the ELISA test demonstrated 83.9% sensitivity and 100% specificity. Thus, the ELISA, developed in our study, may prove as a cheaper alternative to the presently used real time RT-PCR test for detection of human influenza A viruses in clinical specimens, which will be beneficial, especially in the developing countries. Since, the two antibodies identified in this study are reactive to conserved HA epitopes; these may prove as potential therapeutic agents as well.

  1. TRANSFERRIN POLYMORPHISM IN FOUR LOCAL BREEDS OF GOAT IN CENTRAL JAVA, INDONESIA

    Directory of Open Access Journals (Sweden)

    E. Kurnianto

    2012-12-01

    Full Text Available The objectives of this study were to determine the gene frequency and individual heterozygosity of transferrin in four local breeds of goat in Central Java-Indonesia. The number of blood samples were taken from 96 heads of goat, in which each of breeds were 24 samples, those were Kejobong (Purbalingga regency, Ettawa Grade (Purworejo regency, Kacang (Grobogan regency and Jawarandu (Pemalang regency. Polyacrilamide Gel Electrophoresis was performed to detect the bands of blood plasm protein. Gen frequency was calculated using general formula of population genetics. Estimated heterozygosity and individual heterosizygosity were calculated to analysis the equilibrium condition of transferrin. Result showed there was two allele of transferrin, namely TfA and TfB. Gene frequency of TfA was higher than that of TfB. Transferrin gene and genotypes were in disequilibrium of Hardy-Weinberg Law.

  2. Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population.

    LENUS (Irish Health Repository)

    Stack, A G

    2014-08-01

    The transferrin saturation (TSAT) ratio is a commonly used indicator of iron deficiency and iron overload in clinical practice but precise relationships with total and cardiovascular mortality are unclear.

  3. Total mortality by transferrin saturation levels: two general population studies and a metaanalysis

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2011-01-01

    There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown.......There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown....

  4. Effects of transferrin conjugated multi-walled carbon nanotubes in lung cancer delivery

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Rahul Pratap [Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India); Sharma, Gunjan [Genotoxicology and Cancer Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005 (India); Sonali [Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India); Singh, Sanjay [Department of Pharmaceutics, Indian Institute of Technology (BHU), Varanasi 221005 (India); Patne, Shashikant C.U. [Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India); Pandey, Bajarangprasad L. [Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India); Koch, Biplob, E-mail: kochbiplob@gmail.com [Genotoxicology and Cancer Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005 (India); Muthu, Madaswamy S., E-mail: muthubits@rediffmail.com [Department of Pharmaceutics, Indian Institute of Technology (BHU), Varanasi 221005 (India); Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India)

    2016-10-01

    The aim of this study was to develop multi-walled carbon nanotubes (MWCNT) which were covalently conjugated with transferrin by carbodiimide chemistry and loaded with docetaxel as a model drug for effective treatment of lung cancer in comparison with the commercial docetaxel injection (Docel™). D-Alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as amphiphilic surfactant to improve the aqueous dispersity and biocompatibility of MWCNT. Human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) of the docetaxel/coumarin-6 loaded MWCNT. The cellular uptake results of transferrin conjugated MWCNT showed higher efficiency in comparison with free C6. The IC{sub 50} values demonstrated that the transferrin conjugated MWCNT could be 136-fold more efficient than Docel™ after 24 h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells appeared significantly (P < 0.05) in the sub-G1 phase for transferrin conjugated MWCNT in comparison with Docel™. Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™. - Highlights: • It shows the development of transferrin conjugated MWCNT formulation of DTX for the effective treatment of lung cancer. • Evaluated the cellular uptake, cytotoxicity, cellular apoptosis, cell cycle, and ROS level of the DTX/C6 loaded MWCNT. • The IC{sub 50} values demonstrated that the transferrin conjugated MWCNT could be 136-fold more effective than Docel™. • Safety of the DTX formulations were studied by the measurements of ALP, LDH and total protein count levels in BAL fluid. • Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™ in lung cancer delivery.

  5. Effects of transferrin conjugated multi-walled carbon nanotubes in lung cancer delivery

    International Nuclear Information System (INIS)

    Singh, Rahul Pratap; Sharma, Gunjan; Sonali; Singh, Sanjay; Patne, Shashikant C.U.; Pandey, Bajarangprasad L.; Koch, Biplob; Muthu, Madaswamy S.

    2016-01-01

    The aim of this study was to develop multi-walled carbon nanotubes (MWCNT) which were covalently conjugated with transferrin by carbodiimide chemistry and loaded with docetaxel as a model drug for effective treatment of lung cancer in comparison with the commercial docetaxel injection (Docel™). D-Alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as amphiphilic surfactant to improve the aqueous dispersity and biocompatibility of MWCNT. Human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) of the docetaxel/coumarin-6 loaded MWCNT. The cellular uptake results of transferrin conjugated MWCNT showed higher efficiency in comparison with free C6. The IC_5_0 values demonstrated that the transferrin conjugated MWCNT could be 136-fold more efficient than Docel™ after 24 h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells appeared significantly (P < 0.05) in the sub-G1 phase for transferrin conjugated MWCNT in comparison with Docel™. Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™. - Highlights: • It shows the development of transferrin conjugated MWCNT formulation of DTX for the effective treatment of lung cancer. • Evaluated the cellular uptake, cytotoxicity, cellular apoptosis, cell cycle, and ROS level of the DTX/C6 loaded MWCNT. • The IC_5_0 values demonstrated that the transferrin conjugated MWCNT could be 136-fold more effective than Docel™. • Safety of the DTX formulations were studied by the measurements of ALP, LDH and total protein count levels in BAL fluid. • Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™ in lung cancer delivery.

  6. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

    Directory of Open Access Journals (Sweden)

    Bukovsky Antonin

    2008-07-01

    Full Text Available Abstract Background The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction. Methods In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells, placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3 and abnormal (n = 9 pregnancies. Results Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p Conclusion These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction.

  7. Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the brain.

    Science.gov (United States)

    Somani, Sukrut; Blatchford, David R; Millington, Owain; Stevenson, M Lynn; Dufès, Christine

    2014-08-28

    The possibility of using genes as medicines to treat brain diseases is currently limited by the lack of safe and efficacious delivery systems able to cross the blood-brain barrier, thus resulting in a failure to reach the brain after intravenous administration. On the basis that iron can effectively reach the brain by using transferrin receptors for crossing the blood-brain barrier, we propose to investigate if a transferrin-bearing generation 3-polypropylenimine dendrimer would allow the transport of plasmid DNA to the brain after intravenous administration. In vitro, the conjugation of transferrin to the polypropylenimine dendrimer increased the DNA uptake by bEnd.3 murine brain endothelioma cells overexpressing transferrin receptors, by about 1.4-fold and 2.3-fold compared to that observed with the non-targeted dendriplex and naked DNA. This DNA uptake appeared to be optimal following 2h incubation with the treatment. In vivo, the intravenous injection of transferrin-bearing dendriplex more than doubled the gene expression in the brain compared to the unmodified dendriplex, while decreasing the non-specific gene expression in the lung. Gene expression was at least 3-fold higher in the brain than in any tested peripheral organs and was at its highest 24h following the injection of the treatments. These results suggest that transferrin-bearing polypropylenimine dendrimer is a highly promising gene delivery system to the brain. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Targeted Delivery of Amoxicillin to C. trachomatis by the Transferrin Iron Acquisition Pathway.

    Directory of Open Access Journals (Sweden)

    Jun Hai

    Full Text Available Weak intracellular penetration of antibiotics makes some infections difficult to treat. The Trojan horse strategy for targeted drug delivery is among the interesting routes being explored to overcome this therapeutic difficulty. Chlamydia trachomatis, as an obligate intracellular human pathogen, is responsible for both trachoma and sexually transmitted diseases. Chlamydia develops in a vacuole and is therefore protected by four membranes (plasma membrane, bacterial inclusion membrane, and bacterial membranes. In this work, the iron-transport protein, human serum-transferrin, was used as a Trojan horse for antibiotic delivery into the bacterial vacuole. Amoxicillin was grafted onto transferrin. The transferrin-amoxicillin construct was characterized by mass spectrometry and absorption spectroscopy. Its affinity for transferrin receptor 1, determined by fluorescence emission titration [KaffTf-amox = (1.3 ± 1.0 x 108], is very close to that of transferrin [4.3 x 108]. Transmission electron and confocal microscopies showed a co-localization of transferrin with the bacteria in the vacuole and were also used to evaluate the antibiotic capability of the construct. It is significantly more effective than amoxicillin alone. These promising results demonstrate targeted delivery of amoxicillin to suppress Chlamydia and are of interest for Chlamydiaceae and maybe other intracellular bacteria therapies.

  9. Performance of a commercial Chicken-Ovo-transferrin-ELISA on the serum of brown layer chickens infected with Gallibacterium anatis and Streptococcus zooepidemicus

    DEFF Research Database (Denmark)

    Roy, Krisna; Kjelgaard-Hansen, Mads; Pors, Susanne Elisabeth

    2014-01-01

    To evaluate Ovo-transferrin (OTF), a positive acute-phase protein in chickens, as a diagnostic biomarker of selected bacterial infections we checked the performance of a commercial Chicken-OTF-ELISA (ICL, Inc., Portland, OR, USA) by analytical and overlap performances using two groups of serum sa......-infected birds) were >6.4, >3.8 to 6.7, >3.5 to...

  10. Metallofullerenol Inhibits Cellular Iron Uptake by Inducing Transferrin Tetramerization.

    Science.gov (United States)

    Li, Jinxia; Xing, Xueqing; Sun, Baoyun; Zhao, Yuliang; Wu, Zhonghua

    2017-10-18

    Herein, A549 tumor cell proliferation was confirmed to be positively dependent on the concentration of Fe 3+ or transferrin (Tf). Gd@C 82 (OH) 22 or C 60 (OH) 22 effectively inhibited the iron uptake and the subsequent proliferation of A549 cells. The conformational changes of Tf mixed with FeCl 3 , GdCl 3 , C 60 (OH) 22 or Gd@C 82 (OH) 22 were obtained by SAXS. The results demonstrate that Tf homodimers can be decomposed into monomers in the presence of FeCl 3 , GdCl 3 or C 60 (OH) 22 , but associated into tetramers in the presence of Gd@C 82 (OH) 22 . The larger change of SAXS shapes between Tf+C 60 (OH) 22 and Tf+FeCl 3 implies that C 60 (OH) 22 is bound to Tf, blocking the iron-binding site. The larger deviation of the SAXS shape from a possible crystal structure of Tf tetramer implies that Gd@C 82 (OH) 22 is bound to the Tf tetramer, thus disturbing iron transport. This study well explains the inhibition mechanism of Gd@C 82 (OH) 22 and C 60 (OH) 22 on the iron uptake and the proliferation of A549 tumor cells and highlights the specific interactions of a nanomedicine with the target biomolecules in cancer therapy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Innovation in diagnostic imaging services: assessing the potential for value-based reimbursement.

    Science.gov (United States)

    Garrison, Louis P; Bresnahan, Brian W; Higashi, Mitchell K; Hollingworth, William; Jarvik, Jeffrey G

    2011-09-01

    Innovation in the field of diagnostic imaging is based primarily on the availability of new and improved equipment that opens the door for new clinical applications. Payments for these imaging procedures are subject to complex Medicare price control schemes, affecting incentives for appropriate use and innovation. Achieving a "dynamically efficient" health care system-one that elicits a socially optimal amount of innovation-requires that innovators be rewarded in relation to the value they add and can demonstrate with evidence. The authors examine how and whether value-based reimbursement for diagnostic imaging services might better reward innovation explicitly for expected improvements in health and economic outcomes. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

  12. Serum Glutamine Levels as a Potential Diagnostic Biomarker in Sepsis following Surgery for Peritonitis.

    Science.gov (United States)

    Yang, Chun-Ju; Huang, Ting-Shuo; Lee, Tung-Liang; Yang, Kang-Chung; Yuan, Shin-Sheng; Lu, Ruey-Hwa; Hsieh, Chung-Ho; Shyu, Yu-Chiau

    2017-12-31

    Few diagnostic biomarkers for sepsis after emergency peritonitis surgery are available to clinicians, and, thus, it is important to develop new biomarkers for patients undergoing this procedure. We investigated whether serum glutamine and selenium levels could be diagnostic biomarkers of sepsis in individuals recovering from emergency peritonitis surgery. From February 2012 to March 2013, patients who had peritonitis diagnosed at the emergency department and underwent emergency surgery were screened for eligibility. Serum glutamine and selenium levels were obtained at pre-operative, post-operative and recovery time points. The average level of pre-operation serum glutamine was significantly different from that on the recovery day (0.317 ± 0.168 vs. 0.532 ± 0.155 mM, P peritonitis. We recommend including glutamine as a biomarker for sepsis severity assessment in addition to the commonly used clinical indicators.

  13. The potential diagnostic value of serum microRNA signature in patients with pancreatic cancer

    DEFF Research Database (Denmark)

    Johansen, Julia S; Calatayud, Dan; Albieri, Vanna

    2016-01-01

    Biomarkers for early diagnosis of patients with pancreatic cancer (PC) are needed. Our aim was to identify panels of miRNAs in serum in combination with CA 19-9 for use in the diagnosis of PC. Four hundred seventeen patients with PC were included prospectively from Denmark (n = 306) and Germany (n...... than in controls. These miRNAs were tested in the training cohort, and four diagnostic panels were constructed that included 5 or 12 miRNAs (miR-16, -18a, -20a, -24, -25, -27a, -29c, -30a.5p, -191, -323.3p, -345 and -483.5p). Diagnostic accuracy of detecting PC in the training cohort was AUC (Index I 0.......90-0.96) and accuracy 0.88 (0.84-0.91)]. In conclusion, we identified four diagnostic panels based on 5 or 12 miRNAs in serum that could distinguish patients with PC from HS and CP....

  14. Magnetic resonance imaging of the shoulder: a review of potential sources of diagnostic errors

    International Nuclear Information System (INIS)

    Carroll, K.W.; Helms, C.A.

    2002-01-01

    Shoulder magnetic resonance (MR) imaging and MR arthrography are frequently utilized in the evaluation of shoulder pain and instability. The clinical scenario and imaging findings may be confusing to clinicians and radiologists and may present diagnostic challenges for those involved in evaluating and treating shoulder pathology. Often rotator cuff and labral abnormalities may be coexistent, clinical manifestations of denervation syndromes may be confusing to clinicians, and normal anatomic variations, imaging pitfalls, and various artifacts may cause dilemmas for the radiologist. This article will review the most frequently encountered mimickers and pitfalls of MR imaging of the shoulder. (orig.)

  15. On the potential of CARS spectroscopy in low-temperature plasma diagnostics

    International Nuclear Information System (INIS)

    Ambrazyavichyus, A.B.; Gladkov, S.M.; Grigajtis, Yu.P.; Koroteev, N.I.

    1989-01-01

    The principles of coherent anti-Stokes Raman spectroscopy (CARS) and its application to the diagnostics of technological plasmas are briefly discussed. THe CARS spectrometer is described, developed in IPTPE, Caunas for investigations of a nitrogen plasma stream generated by an industrial plasmatron, and several CARS spectra of nitrogen molecules are presented. As the CARS signal from vibrational-rotational energy levels decreases substantially at plasma temperatures above 2000 K, an alternative scheme using electronlevels of atoms or ions has to be used. To test the method, CARS signals from the lines of the first nitrogen ion were studied in a low-voltage spark discharge. (J.U.)

  16. A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Peijs, L; Vinberg, M

    2015-01-01

    as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6-12-month period and in 40 age...... subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver...

  17. Seminal transferrin in the seminal quality evaluation of hemodialytic patients

    Directory of Open Access Journals (Sweden)

    Gilmar Pereira Silva

    2018-03-01

    Full Text Available Objective: to verify the association between seminal quality and seminal transferrin (ST level and fertility index in patients undergoing chronic hemodialysis (CH. Material and methods: This is a cross-sectional study in a group of 60 men (case undergoing CH for more than 6 months, and a group of 30 healthy men (control, aged 18-60 years, without clinical or laboratory signs of infection/inflammation. Spermiogram was performed, fertility index (FI was calculated and ST and sex hormones (SH levels were measured, including follicle-stimulating hormone, luteinizing hormone, total testosterone, and prolactin. Results: All individuals were eugonadal. No differences for age (49.47 ± 5.56, 47.90 ± 6.2, p = 0.22 were observed between cases and controls, whereas there were significant differences between the individuals in the case and control groups with respect to the mean FI (p = 0.000, seminal parameters (SP (p = 0.000, and ST levels (40.12 ± 08.25 vs 73.32 ± 06.8, p = 0.000. ST levels were correlated with FI (r = 0.787, p = 0.00 and SP (motility: r = 0.857, p = 0.000; vitality: r = 0.551, p = 0.000; density: r = 0.850, p = 0.000; normal morphology: r = 0.386, p = 0.000. Linear regression model showed relationship of ST levels with total sperm motility (R2 = 0.701; p = 0.000 and and FI (R2 = 0.569; p = 0.000. Conclusions: Our results suggest that seminal quality is associated with ST levels and FI and that it can be used the initial investigation of subfertility/infertility of patients undergoing chronic hemodialysis..

  18. Electrosynthesized MIPs for transferrin: Plastibodies or nano-filters?

    Science.gov (United States)

    Zhang, Xiaorong; Yarman, Aysu; Erdossy, Júlia; Katz, Sagie; Zebger, Ingo; Jetzschmann, Katharina J; Altintas, Zeynep; Wollenberger, Ulla; Gyurcsányi, Róbert E; Scheller, Frieder W

    2018-05-15

    Molecularly imprinted polymer (MIP) nanofilms for transferrin (Trf) have been synthesized on gold surfaces by electro-polymerizing the functional monomer scopoletin in the presence of the protein target or around pre-adsorbed Trf. As determined by atomic force microscopy (AFM) the film thickness was comparable with the molecular dimension of the target. The target (re)binding properties of the electro-synthesized MIP films was evaluated by cyclic voltammetry (CV) and square wave voltammetry (SWV) through the target-binding induced permeability changes of the MIP nanofilms to the ferricyanide redox marker, as well as by surface plasmon resonance (SPR) and surface enhanced infrared absorption spectroscopy (SEIRAS) of the immobilized protein molecules. For Trf a linear concentration dependence in the lower micromolar range and an imprinting factor of ~5 was obtained by SWV and SPR. Furthermore, non-target proteins including the iron-free apo-Trf were discriminated by pronounced size and shape specificity. Whilst it is generally assumed that the rebinding of the target or of cross-reacting proteins exclusively takes place at the polymer here we considered also the interaction of the protein molecules with the underlying gold transducers. We demonstrate by SWV that adsorption of proteins suppresses the signal of the redox marker even at the bare gold surface and by SEIRAS that the treatment of the MIP with proteinase K or NaOH only partially removes the target protein. Therefore, we conclude that when interpreting binding of proteins to directly MIP-covered gold electrodes the interactions between the protein and the gold surface should also be considered. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. 201Th chloride scintiscanning in myocardial infarction - correlation with ECG findings - diagnostic potential

    International Nuclear Information System (INIS)

    Kostka, I.

    1980-01-01

    The author intended to find out in how far myocardial scintiscanning with 201 Th chloride is a necessary auxiliary investigation in diagnosing acute myocardial infarction and whether there are correlations between ECG, increase of enzyme levels, and pressure measured in the lesser circulatory system. The scintiscans were evaluated by a new method: Defect sizes were determined using a transparent template and recorded in angular degrees. Also the reduced activity was considered. Especially posterior myocardial infarctions can be localized more easily and clearly by means of myocardial scintiscanning at rest, and also infarction sizes can be judged more easily. For a diagnosis of small myocardial infarctions or in patients with a block in their ECG picture, scintiscanning is a necessary part of the diagnostic spectrum. The findings of myocardial scintiscanning correspond well with those of other methods. As for the pressure increase in the lesser circulatory system, it is well correlated with the defect size shown by the scintiscan. 201 Th scintiscanning offers a good diagnostic possibility in those myocardial infarctions where ECG findings are ambiguous. (orig./MG) [de

  20. ECHOGRAPHY POTENTIAL IN DIAGNOSTICS OF THE KNEE JOINT IMPAIRMENT IN THE EVENT OF THE JUVENILE ARTHRITIDES

    Directory of Open Access Journals (Sweden)

    N.V. Osipova

    2008-01-01

    Full Text Available The juvenile rheumatoid arthritis (JRA is one of the most widely spread rheumatic diseases among children, which is characterized by the steady progressive run, rapidly leading to the disability. Among numerous JRA manifestations, one of the leading is the joint syndrome with children mostly suffering from the knee joint impairment. With JRA, the initial changes in the joints affect the joint tissues and articular cartilage, while the bone changes evolve at the late stages of the disease. As a result, the echography plays an important role in the early arthritides diagnostics if compared to the x ray study and computerized tomography. To identify the typical features of the knee joint impairment, 97 children with JRA and 16 children with the juvenile spondyl arthritis (JSA underwent the high pitched linear transducer assisted echography. The overwhelming majority of patients showed the changes in the hyaline cartilage. The hyperechoic enlargements in the depth of the cartilage were typical of JRA, while the cartilage thinning was typical of JSA. About a half of the patients showed the effusion. Over a third of the patients showed the changes in the cortical layer of the articular bone surface.Key words: juvenile rheumatoid arthritis, juvenile spondyl arthritis, diagnostics, knee joint echography, children.

  1. The role of serum transferrin receptor in the diagnosis of iron deficiency.

    Science.gov (United States)

    Remacha, A F; Sarda, M P; Parellada, M; Ubeda, J; Manteiga, R

    1998-11-01

    Iron deficiency anemia (IDA) is often associated with inflammatory disorders. The most conventional parameters of iron metabolism are therefore affected, making the evaluation of iron status difficult. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes. The aim of this study was to investigate the role of sTfR in differentiating IDA with inflammatory features. A diagnostic study of sTfR measured by immunoassay was carried out in IDA and anemia of chronic disorders (ACD). The cut-off points of sTfR and the ratio of sTfR/serum ferritin, which were obtained after comparing IDA and ACD, were applied to a group of 64 patients with mixed iron patterns (MIX) (16 with ACD and 48 with IDA). The best cut-off point of sTfR between IDA and ACD was 4.7 mg/L. Applying this cut-off to the MIX group, an efficiency of 87% was obtained (sensitivity 92% and specificity 81%). This level of sTfR correctly classified 53 out of 64 cases of the MIX group (83%). Using the ratio of sTfRx 100/serum ferritin, the best cut-off point was 8 (efficiency 100%), which correctly classified 62 out of 64 cases of the MIX group (97%). This study demonstrates that sTfR in conjunction with other iron parameters is very useful in iron deficiency evaluation, especially in hospital practice. Iron treatment should be considered in patients with mixed patterns of iron status, in which the diagnosis of IDA versus ACD is difficult, when the levels of sTfR exceed the cut-off point.

  2. Aluminum access to the brain: A role for transferrin and its receptor

    International Nuclear Information System (INIS)

    Roskams, A.J.; Connor, J.R.

    1990-01-01

    The toxicity of aluminum in plant and animal cell biology is well established, although poorly understood. Several recent studies have identified aluminum as a potential, although highly controversial, contributory factor in the pathology of Alzheimer's disease, amyotrophic lateral sclerosis, and dialysis dementia. For example, aluminum has been found in high concentrations in senile plaques and neurofibrillary tangles, which occur in the brains of subjects with Alzheimer's disease. However, a mechanism for the entry of aluminum (Al 3+ ) into the cells of the central nervous system (CNS) has yet to be found. Here the authors describe a possible route of entry for aluminum into the cells of the CNS via the same high-affinity receptor-ligand system that has been postulated for iron (Fe 3 ) aluminum is able to gain access to the central nervous system under normal physiological conditions. Furthermore, these data suggest that the interaction between transferrin and its receptor may function as a general metal ion regulatory system in the CNS, extending beyond its postulated role in iron regulation

  3. Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

    Directory of Open Access Journals (Sweden)

    Xi Lin

    2017-11-01

    Full Text Available Photodynamic therapy (PDT has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA and carboxymethyl chitosan (CMC nanoparticle loaded with a photosensitizer hypocrellin A (HA, named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

  4. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Jakobsen, Kristine Raaby; Paulsen, Birgitte Sandfeld; Bæk, Rikke

    2015-01-01

    Background: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell...... control subjects based on the differential display of exosomal protein markers. Methods: Plasma was isolated from 109 NSCLC patients with advanced stage (IIIa–IV) disease and 110 matched control subjects initially suspected of having cancer, but diagnosed to be cancer free. The Extracellular Vesicle Array...... (EV Array) was used to phenotype exosomes directly from the plasma samples. The array contained 37 antibodies targeting lung cancer-related proteins and was used to capture exosomes, which were visualised with a cocktail of biotin-conjugated CD9, CD63 and CD81 antibodies. Results: The EV Array...

  5. Opportunities for new CT contrast agents to maximize the diagnostic potential of emerging spectral CT technologies.

    Science.gov (United States)

    Yeh, Benjamin M; FitzGerald, Paul F; Edic, Peter M; Lambert, Jack W; Colborn, Robert E; Marino, Michael E; Evans, Paul M; Roberts, Jeannette C; Wang, Zhen J; Wong, Margaret J; Bonitatibus, Peter J

    2017-04-01

    The introduction of spectral CT imaging in the form of fast clinical dual-energy CT enabled contrast material to be differentiated from other radiodense materials, improved lesion detection in contrast-enhanced scans, and changed the way that existing iodine and barium contrast materials are used in clinical practice. More profoundly, spectral CT can differentiate between individual contrast materials that have different reporter elements such that high-resolution CT imaging of multiple contrast agents can be obtained in a single pass of the CT scanner. These spectral CT capabilities would be even more impactful with the development of contrast materials designed to complement the existing clinical iodine- and barium-based agents. New biocompatible high-atomic number contrast materials with different biodistribution and X-ray attenuation properties than existing agents will expand the diagnostic power of spectral CT imaging without penalties in radiation dose or scan time. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic

    Directory of Open Access Journals (Sweden)

    Y. Lalatonne

    2010-01-01

    Full Text Available A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI and a therapeutic agent (bisphosphonates into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe2O3 nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2∗ contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63 show that γFe2O3@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.

  7. Potential application of new diagnostic methods for controlling bovine Tuberculosis in Brazil

    Directory of Open Access Journals (Sweden)

    Luciana dos Santos Medeiros

    2010-10-01

    Full Text Available Bovine tuberculosis, a chronic infection in cattle caused by Mycobacterium bovis, remains an economic and public health problem for several countries. Due to its economic impact on international trade, contagious nature, and implications for human health, global programs to eradicate the disease were implemented worldwide. Those programs are based on slaughtering PPD-reactive animals. Despite the National Programs in Brazil, complete eradication has not been achieved, and the disease remains, albeit at a lower prevalence. The central purpose of this review is to address diagnostic tests for tuberculosis. Considering the course of the infection in cattle, at least two tests, ideally complementary to one another, may be necessary for an adequate diagnosis: the first based on the cellular response, and the second capable of identifying anergic animals by detection of specific anti-M.bovis antibodies.

  8. Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

    Science.gov (United States)

    Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

    2016-08-15

    A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

  9. Potential Child Abuse Screening in Emergency Department; a Diagnostic Accuracy Study

    Directory of Open Access Journals (Sweden)

    Hossein Dinpanah

    2017-01-01

    Full Text Available Introduction: Designing a tool that can differentiate those at risk of child abuse with great diagnostic accuracyis of great interest. The present study was designed to evaluate the diagnostic accuracy of Escape instrumentin triage of at risk cases of child abuse presenting to emergency department (ED. Methods: The present diagnosticaccuracy study performed on 6120 of the children under 16 years old presented to ED during 3 years,using convenience sampling. Confirmation by the child abuse team (pediatrician, a socialworker, and a forensicphysician was considered as the gold standard. Screening performance characteristics of Escape were calculatedusing STATA 21. Results: 6120 children with the mean age of 2.19 § 1.12 years were screened (52.7% girls.137 children were suspected victims of child abuse. Based on child abuse team opinion, 35 (0.5% children wereconfirmed victims of child abuse. Sensitivity, specificity, positive and negative likelihood ratio and positive andnegative predictive values of this test with 95% CI were 100 (87.6 – 100, 98.3 (97.9 – 98.6, 25.5 (18.6 – 33.8, 100(99.9 – 100, 0.34 (0.25 – 0.46, and 0 (0 – NAN, respectively. Area under the ROC curve was 99.2 (98.9 – 99.4.Conclusion: It seems that Escape is a suitable screening instrument for detection of at risk cases of child abusepresenting to ED. Based on the results of the present study, the accuracy of this screening tool is 99.2%, which isin the excellent range.

  10. The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body.

    Directory of Open Access Journals (Sweden)

    Christal A Worthen

    2014-03-01

    Full Text Available Fine tuning of body iron is required to prevent diseases such as iron-overload and anemia. The putative iron-sensor, transferrin receptor 2 (TfR2, is expressed in the liver and mutations in this protein result in the iron-overload disease Type III hereditary hemochromatosis (HH. With the loss of functional TfR2, the liver produces about two-fold less of the peptide hormone hepcidin, which is responsible for negatively regulating iron uptake from the diet. This reduction in hepcidin expression leads to the slow accumulation of iron in the liver, heart, joints, and pancreas and subsequent cirrhosis, heart disease, arthritis, and diabetes. TfR2 can bind iron-loaded transferrin in the bloodstream, and hepatocytes treated with transferrin respond with a two-fold increase in hepcidin expression through stimulation of the BMP-signaling pathway. Loss of functional TfR2 or its binding partner, the original HH protein (HFE, results in a loss of this transferrin-sensitivity. While much is known about the trafficking and regulation of TfR2, the mechanism of its transferrin-sensitivity through the BMP-signaling pathway is still not known.

  11. Radiogallium localization in tumors: blood binding and transport and the role of transferrin

    International Nuclear Information System (INIS)

    Vallabhajosula, S.R.; Harwig, J.F.; Siemsen, J.K.; Wolf, W.

    1980-01-01

    As a crucial step toward the understanding of the tumor localization of gallium, we have re-investigated its binding and transport in blood. The studies were performed in vivo by injection of gallium-67 citrate in rabbits, and in vitro by incubation of gallium-67 citrate with individual plasma proteins. By ultrafiltration and gel filtration chromatography, rabbit plasma samples showed essentially complete protein binding, whereas dialysis indicated considerable nonprotein-bound gallium, the amount depending on the dialysis medium. According to electrophoresis, total binding was inversely proportional to electrophoresis time. Affinity chromatography showed all gallium to be bound to transferrin, whereas electrophoresis caused continuous dissociation of gallium from transferrin, with the resulting unbound radioactivity appearing in various other protein bands. Similarly, the binding of gallium to transferrin in the in vitro incubation studies was inversely proportional to electrophoresis time, whereas ultrafiltration and gel filtration chromatography showed all gallium to be transferrin-bound. No binding of gallium to other proteins, such as albumin, was observed. This study demonstrates that gallium at the tracer level in blood is exclusively bound to and transported by transferrin, and indicates that electrophoresis and dialysis of easily dissociable metal complexes are subject to significant artifacts. Accurate determination of protein binding of radiopharmaceuticals requires a combination of analytical techniques and cautious interpretation of the results

  12. Transferrin-derived synthetic peptide induces highly conserved pro-inflammatory responses of macrophages.

    Science.gov (United States)

    Haddad, George; Belosevic, Miodrag

    2009-02-01

    We examined the induction of macrophage pro-inflammatory responses by transferrin-derived synthetic peptide originally identified following digestion of transferrin from different species (murine, bovine, human N-lobe and goldfish) using elastase. The mass spectrometry analysis of elastase-digested murine transferrin identified a 31 amino acid peptide located in the N2 sub-domain of the transferrin N-lobe, that we named TMAP. TMAP was synthetically produced and shown to induce a number of pro-inflammatory genes by quantitative PCR. TMAP induced chemotaxis, a potent nitric oxide response, and TNF-alpha secretion in different macrophage populations; P338D1 macrophage-like cells, mouse peritoneal macrophages, mouse bone marrow-derived macrophages (BMDM) and goldfish macrophages. The treatment of BMDM cultures with TMAP stimulated the production of nine cytokines and chemokines (IL-6, MCP-5, MIP-1 alpha, MIP-1 gamma, MIP-2, GCSF, KC, VEGF, and RANTES) that was measured using cytokine antibody array and confirmed by Western blot. Our results indicate that transferrin-derived peptide, TMAP, is an immunomodulating molecule capable of inducing pro-inflammatory responses in lower and higher vertebrates.

  13. Present-day potentialities of endoscopic diagnostics and treatment of early cancer in respiratory and digestive tracts

    Science.gov (United States)

    Sokolov, Victor V.; Zharkova, Natalia N.; Filonenko, E. V.; Telegina, L. V.; Karpova, E. S.

    1999-12-01

    The paper presents the latest potentialities of the endoscopic fluorescent diagnostics as well as endoscopic electric-, laser surgery and photodynamic therapy (PDT) of the early cancer in the respiratory and digestive tracts. We present in detail indication and factors determining the application of the endoscopic resection of the tumor. The advantages of the combination application of PDT, electro-, Nd:YAG laser surgery and brachitherapy are stressed. The near and remote results of endoscopic treatment of the early cancer in larynx (37), lung (109), esophagus (39) and stomach (58) are shown.

  14. Tertiary structural changes and iron release from human serum transferrin.

    Science.gov (United States)

    Mecklenburg, S L; Donohoe, R J; Olah, G A

    1997-08-01

    Iron release from human serum transferrin was investigated by comparison of the extent of bound iron, measured by charge transfer absorption band intensity (465 nm), with changes observed by small-angle solution X-ray scattering (SAXS) for a series of equilibrated samples between pH 5.69 and 7.77. The phosphate buffers used in this study promote iron release at relatively high pH values, with an empirical pK of 6.9 for the convolved release from the two sites. The spectral data reveal that the N-lobe release is nearly complete by pH 7.0, while the C-lobe remains primarily metal-laden. Conversely, the radius of gyration, Rg, determined from the SAXS data remains constant between pH 7.77 and 7.05, and the evolution of Rg between its value observed for the diferric protein at pH 7.77 (31.2+/-0.2 A) and that of the apo protein at pH 5.69 (33.9+/-0.4 A) exhibits an empirical pK of 6.6. While Rg is effectively constant in the pH range associated with iron release from the N-lobe, the radius of gyration of cross-section, Rc, increases from 16.9+/-0.2 A to 17.6+/-0.2 A. Model simulations suggest that two different rotations of the NII domain relative to the NI domain about a hinge deep in the iron-binding cleft of the N-lobe, one parallel with and one perpendicular to the plane of the iron-binding site, can be significantly advanced relative to their holo protein positions while yielding constant Rg and increased Rc values consistent with the scattering data. Rotation of the CII domain parallel with the C-lobe iron-binding site plane can partially account for the increased Rg values measured at low pH; however, no reasonable combined repositioning of the NII and CII domains yields the experimentally observed increase in Rg.

  15. Diagnostic potential of nested PCR, galactomannan EIA, and beta-D-glucan for invasive aspergillosis in pediatric patients.

    Science.gov (United States)

    Badiee, Parisa; Alborzi, Abdolvahab; Karimi, Mahammad; Pourabbas, Bahman; Haddadi, Pedram; Mardaneh, Jalal; Moieni, Mahsa

    2012-04-13

    Limited specific data and investigations are available for invasive aspergillosis (IA) in pediatric patients. We evaluated the diagnostic potential of three noninvasive tests including the Platelia Aspergillus EIA kit for using galactomannan antigen, (1,3)-β-D-glucan Detection Reagent Kit, and nested-PCR for Aspergillus DNA in sera. We evaluated the diagnostic potential of three noninvasive tests including EIA for galactomannan antigen  (Platelia Aspergillus), nested  PCR assay for Aspergillus DNA and test for (1→3)-β-D-glucan (Glucatell assay Kit). All pediatric patients treated at the hematology/oncology unit who were at increased risk of developing invasive aspergillosis were enrolled. Clinical samples were examined for Aspergillus infections by mycological methods. Serial blood samples were collected twice weekly and evaluated by noninvasive tests. We analyzed 230 consecutive blood samples from 62 pediatric patients. The incidence rate of invasive aspergillosis in the patients was found to be 27.4%, and the etiologic agents were Aspergillus flavus, Aspergillus fumigatus, and Aspergillus spp.  The sensitivity, specificity, positive and negative predictive values, and likelihood ratios for positive and negative results of galactomannan in patients with proven and probable IA were 90%, 92%, 81.8%, 96%, 11.25, and 0.1; for beta-D-glucan they were 50%, 46%, 26%, 70.6%, 0.9, 0.9; and for nested-PCR they were 80%, 96.2%, 88.9%, 92.6%, 21, and 0.2, respectively. The conventional methods are not able to detect IA, due to the lack of valid and proper sampling. Galactomannan and nested-PCR tests in serum, with enough accuracy and reliability, can serve as noninvasive methods for the detection of IA in pediatric patients. However, the beta-D-glucan test cannot serve as an efficient diagnostic tool in those with hematologic disorders. 

  16. An unusual case of iron deficiency anemia is associated with extremely low level of transferrin receptor.

    Science.gov (United States)

    Hao, Shuangying; Li, Huihui; Sun, Xiaoyan; Li, Juan; Li, Kuanyu

    2015-01-01

    A case study of a female patient, diagnosed with iron deficiency anemia, was unresponsive to oral iron treatment and only partially responsive to parenteral iron therapy, a clinical profile resembling the iron-refractory iron deficiency anemia (IRIDA) disorder. However, the patient failed to exhibit microcytic phenotype, one of the IRIDA hallmarks. Biochemical assays revealed that serum iron, hepcidin, interluekin 6, and transferrin saturation were within the normal range of references or were comparable to her non-anemic offspring. Iron contents in serum and red blood cells and hemoglobin levels were measured, which confirmed the partial improvement of anemia after parenteral iron therapy. Strikingly, serum transferrin receptor in patient was almost undetectable, reflecting the very low activity of bone-marrow erythropoiesis. Our data demonstrate that this is not a case of systemic iron deficiency, but rather cellular iron deficit due to the low level of transferrin receptor, particularly in erythroid tissue.

  17. Tumor necrosis factor-alpha is a potential diagnostic biomarker for chronic neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Xu, Jun; E, Xiaoqiang; Liu, Huiyong; Li, Feng; Cao, Yanhui; Tian, Jun; Yan, Jinglong

    2015-05-19

    Neuropathic pain (NP) is one of the most common complications after spinal cord injury (SCI), but no protein biomarkers has ever been introduced into clinical diagnosis. Previous studies implicated that toll-like receptor (TLR) 4 played a critical role in the development of NP in animal SCI models. Here, a total of 140 participants were recruited, 70 of them were SCI-NP subject and the rest 70 controls did not show neuropathic symptoms. TLR4 was upregulated significantly in SCI-NP patients compared with SCI-noNP subjects. Furthermore, we measured the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), two TLR4 downstream pro-inflammatory cytokines, to assess their diagnostic values. Receiver operating characteristics (ROC) analysis revealed that TNF-α had great potential advantages to predict the progression of neuropathy, the risks of NP were strongly increased in SCI subjects with higher levels of TNF-α (odds ratio: 4.92; 95% confidence interval: 1.89-12.32). These results suggested neuro-immune activation contributed to the development of neuropathic disorder after SCI, and TNF-α could be a potential sensitive diagnostic biomarker for chronic neuropathic pain in SCI patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Assessment of the potential diagnostic value of serum p53 antibody for cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    Full Text Available BACKGROUND: Mutant p53 protein over-expression has been reported to induce serum antibodies against p53. We assessed the diagnostic precision of serum p53 (s-p53 antibodies for diagnosis of cancer patients and compared the positive rates of the s-p53 antibody in different types of cancers. METHODS: We systematically searched PubMed and Embase, through May 31, 2012. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy. The positive likelihood ratio (PLR and negative likelihood ratio (NLR were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs and Area under the curve(AUC. Meta regression and subgroup analyses were done, and heterogeneity and publication bias were assessed. RESULTS: Of 1089 studies initially identified, 100 eligible studies with 23 different types of tumor met the inclusion criteria for the meta-analysis (cases = 15953, controls = 8694. However, we could conduct independent meta analysis on only 13 of 36 types of tumors. Approximately 56% (56/100 of the included studies were of high quality (QUADAS score≥8. The summary estimates for quantitative analysis of serum p53 antibody in the diagnosis of cancers were: PLR 5.75 (95% CI: 4.60-7.19, NLR 0.81 (95%CI: 0.79-0.83 and DOR 7.56 (95% CI: 6.02-9.50. However, for the 13 types of cancers on which meta-analysis was conducted, the ranges for PLR (2.33-11.05, NLR (0.74-0.97, DOR (2.86-13.80, AUC(0.29-0.81, and positive rate (4.47%-28.36% indicated significant heterogeneity. We found that breast, colorectal, esophageal, gastric, hepatic, lymphoma, lung and ovarian cancer had relatively reasonable diagnostic accuracy. The remaining results of the five types of cancers suggested that s-p53 antibody had limited value. CONCLUSIONS: The current evidence suggests that s-p53 antibody has potential diagnostic value for cancer, especially for breast, colorectal, esophageal, gastric, hepatic

  19. Inactivation of transferrin iron binding capacity by the neutrophil myeloperoxidase system

    International Nuclear Information System (INIS)

    Clark, R.A.; Pearson, D.W.

    1989-01-01

    Human serum apotransferrin was exposed to the isolated myeloperoxidase-H2O2-halide system or to phorbol ester-activated human neutrophils. Such treatment resulted in a marked loss in transferrin iron binding capacity as well as concomitant iodination of transferrin. Each component of the cell-free system (myeloperoxidase, H2O2, iodide) or neutrophil system (neutrophils, phorbol ester, iodide) was required in order to observe these changes. In the cell-free system, the H2O2 requirement was fulfilled by either reagent H2O2 or the peroxide-generating system glucose oxidase plus glucose. Both loss of iron binding capacity and transferrin iodination by either the myeloperoxidase system or activated neutrophils were blocked by azide or catalase. The isolated peroxidase system had an acidic pH optimum, whereas the intact cell system was more efficient at neutral pH. The kinetics of changes in iron binding capacity and iodination closely paralleled one another, exhibiting t1/2 values of less than 1 min for the myeloperoxidase-H2O2 system, 3-4 min for the myeloperoxidase-glucose oxidase system, and 8 min for the neutrophil system. That the occupied binding site is protected from the myeloperoxidase system was suggested by (1) a failure to mobilize iron from iron-loaded transferrin, (2) an inverse correlation between initial iron saturation and myeloperoxidase-mediated loss of iron binding capacity, and (3) decreased myeloperoxidase-mediated iodination of iron-loaded versus apotransferrin. Since as little as 1 atom of iodide bound per molecule of transferrin was associated with substantial losses in iron binding capacity, there appears to be a high specificity of myeloperoxidase-catalyzed iodination for residues at or near the iron binding sites. Amino acid analysis of iodinated transferrin (approximately 2 atoms/molecule) demonstrated that iodotyrosine was the predominant iodinated species

  20. The human immune response to streptococcal extracellular antigens: clinical, diagnostic, and potential pathogenetic implications.

    Science.gov (United States)

    Johnson, Dwight R; Kurlan, Roger; Leckman, James; Kaplan, Edward L

    2010-02-15

    Determination of an immune response to group A Streptococcus (GAS) antigens, frequently anti-streptolysin O and anti-DNase B, is crucial for documentation of bona fide GAS infection. Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood. Pediatric study participants (n = 160) were followed during a 2-year study with monthly throat cultures (n = 3491) and blood samples (n = 1679) obtained every 13 weeks. Recovered GAS were characterized; serum anti-streptolysin O and anti-DNase B antibody titers were determined. Antibody titers and GAS culture results were temporally correlated and analyzed. The analyses clearly document, in some instances for the first time, that an increase in antibody titer more accurately defines infection than does an absolute titer (eg, "upper limit of normal"), that antibody titers can remain elevated for many months even without GAS, and that some individuals may harbor GAS continuously for months or years without symptoms of infection and without an associated immune response. Measuring 2 different antibodies is more accurate in defining infection. Single time-point cultures and single antibody titers are often misleading. Sequential samples more accurately define infection, allowing correlation of titer increases with temporal confirmation of GAS acquisition. Understanding kinetics of the immune response(s) to GAS infection is necessary in formulating accurate clinical diagnostic conclusions, to appropriate design of clinical and epidemiological studies examining the association of GAS with subsequent sequelae, and to providing insight into pathogenetic mechanisms associated with this important human pathogen.

  1. Assessment of a Radioimmunological Method to Measure Transferrin in Seminal Plasm

    International Nuclear Information System (INIS)

    Mallea Sanchez, L.; Estevez Gandara, A.; Navaroli Fernandez, F.; Machado Curbelo, A.J.

    1986-01-01

    A specific antiserum against human transferrin was obtained. It was titrated and used to develop a radioimmunological method to measure transferrin in seminal plasm, since the concentration of that protein could be a useful marker of testicular function in the clinical management of male infertility. The method showed good precision, accurateness and sensitivity, when it was assessed by standard statistical methods and accordingly it seems to be adequate for the intended purposes. The assessment of its value in the diagnosis and therapy of male infertility, will be the subject of future work. (author). 14 refs

  2. Iron metabolism in BeWo chorion carcinoma cells. Transferrin-mediated uptake and release of iron

    NARCIS (Netherlands)

    van der Ende, A.; du Maine, A.; Simmons, C. F.; Schwartz, A. L.; Strous, G. J.

    1987-01-01

    Growing human choriocarcinoma BeWo b24 cells contain 1.5 X 10(6) functional cell surface transferrin binding sites and 2.0 X 10(6) intracellular binding sites. These cells rapidly accumulate iron at a rate of 360,000 iron atoms/min/cell. During iron uptake the transferrin and its receptor recycle at

  3. Torcular pseudomass: a potential diagnostic pitfall in infants and young children

    Energy Technology Data Exchange (ETDEWEB)

    Sampaio, Luisa [Centro Hospitalar de Sao Joao, Department of Neuroradiology, Oporto (Portugal); Morana, Giovanni; Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea [Istituto Giannina Gaslini, Neuroradiology Unit, Genoa (Italy); Leao, Miguel [Centro Hospitalar de Sao Joao, Neuropediatric Unit, Oporto (Portugal)

    2017-02-15

    Incidental findings on brain MRI may constitute a diagnostic pitfall. We observed an incidental extra-axial midline rounded pseudomass between the torcular Herophili and the occipital squama, with spontaneous resolution, which we called ''torcular pseudomass.'' We investigated the frequency, imaging features, natural history and developmental background of this finding in a large group of infants and young children. We conducted a single-center retrospective study by reviewing all brain MRIs performed in children younger than 3 years between 2007 and 2013 in a specialized pediatric hospital. We looked for soft tissue (minimum 2 mm thick) interposed between the torcula and the occipital squama on midsagittal T1 and T2 images; we recorded the maximal diameters and outcome. Of 2,283 the children who had brain MRIs during the study period, 291 (12.7%, 95% confidence interval [CI] 0.11, 0.14) presented with a torcular pseudomass (median age 4 months, range 0 days to 35 months, 56% male). MRI features were the same in all of these children: T1 isointensity and T2 hyperintensity to the cerebral cortex, facilitated diffusion on diffusion-weighted imaging and apparent diffusion coefficient maps, and contrast enhancement. The median diameters were: anteroposterior, 5.8 mm; transverse, 10.5 mm; cranio-caudal, 20.6 mm. Follow-up MRI was available in 34.7% (95% CI: 0.20, 0.40) of the children; median follow-up time was 18 months. Among these children, 35.6% (95% CI: 0.26, 0.45) had total involution, 52.5% (95% CI: 0.26, 0.62) had partial involution and 4.1% (95% CI: 0.05, 0.18) showed stability. Redundant soft tissue in the torcular region, or torcular pseudomass, is not an infrequent finding in infants and young children. It should be considered a physiological tissue, reflecting the postnatal developmental process of the brain and cranial vault, without the need for further investigation or follow-up imaging studies. (orig.)

  4. Diagnostic potentialities of pneumomediastinography and selective phlebography in the evaluation of thymus evolution in myasthenia

    Energy Technology Data Exchange (ETDEWEB)

    Vasil' ev, V.N.; Bel' chikova, N.S.; Kuksinskij, V.E. (Leningradskij Inst. Usovershenstvovaniya Vrachej (USSR))

    1983-01-01

    Based on an analysis of X-ray, intraoperative and histological findings in 124 operated on patients (thymectomy) with myasthenia the authors describe potentialities of pneumomediastinography (PMG) (pheumomediastinotomography-PMTG) in the determination of its main variants (hyperplasia, involution, tumor). Clear knowledge of the variants of x-ray image of the normal anatomical structures of the anterior mediastinum and age peculiarities of the thymus for correct interpretation of pneumomediastinograms is necessary. The importance of selective phlebography of the thymus for differential diagnosis of thymomas and nodular indurations of the fatty tissue in the anterior mediastinum, thymomas and fatty involution of the thymus, residual thymus and zones of fibrous-adipose tissue in the mediastinum is stressed. Selective phlebography is a simple and safe method that adds to PMG (PMTG) potentialities in the evaluation of thymus evolution in myasthenia.

  5. Diagnostic potentialities of pneumomediastinography and selective phlebography in the evaluation of thymus evolution in myasthenia

    International Nuclear Information System (INIS)

    Vasil'ev, V.N.; Bel'chikova, N.S.; Kuksinskij, V.E.

    1983-01-01

    Basing on an analysis of X-ray, intraoperative and histological findings in 124 operated on patients (thymectomy) with myasthenia the authors describe potentialities of pneumomediastinography (PMG) (pheumomediastinotomography-PMTG) in the determination of its main variants (hyperplasia, involUtion, tumor). Clear knowledge of the variants of x-ray image of the normal anatomical structures of the anterior mediastinum and age peculiarities of the thymus for correct interpretation of pneumomediastinograms is necessary. The importance of selective phlebography of the thymus for differential diagnosis of thymomas and nodular indurations of the fatty tissue in the anterior mediastinum, thymomas and fatty involution of the thymus, residual thymus and zones of fibrous-adipose tissue in the mediastinum is stressed. Selective phlebography is a simple and safe method that adds to PMG (PMTG) potentialities in the evaluation of thymus evolution in myasthenia

  6. Transferrin-polycation-mediated introduction of DNA into human leukemic cells: Stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels

    International Nuclear Information System (INIS)

    Cotten, M.; Laengle-Rouault, F.; Kirlappos, H.; Wagner, E.; Mechtler, K.; Zenke, M.; Beug, H.; Birnstiel, M.L.

    1990-01-01

    The authors have subverted a receptor-mediated endocytosis event to transport genes into human leukemic cells. By coupling the natural iron-delivery protein transferrin to the DNA-binding polycations polylysine or protamine, they have created protein conjugates that bind nucleic acids and carry them into the cell during the normal transferrin cycle. They demonstrate here that this procedure is useful for a human leukemic cell line. They enhanced the rate of gene delivery by (i) increasing the transferrin receptor density through treatment of the cells with the cell permeable iron chelator desferrioxamine, (ii) interfering with the synthesis of heme with succinyl acetone treatment, or (iii) stimulating the degradation of heme with cobalt chloride treatment. Consistent with gene delivery as an endocytosis event, they show that the subsequent expression in K-562 cells of a gene included in the transported DNA depends upon the cellular presence of the lysosomotropic agent chloroquine. By contrast, monensin blocks transferrinfection, as does incubation of the cells at 18 degree C

  7. Circulating microRNAs as a Novel Class of Potential Diagnostic Biomarkers in Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Kichukova Tatyana M.

    2015-12-01

    Full Text Available Neuropsychiatric diseases, such as schizophrenia, bipolar disorder (BD, major depressive disorder (MDD and autism spectrum disorder (ASD, are a huge burden on society, impairing the health of those affected, as well as their ability to learn and work. Biomarkers that reflect the dysregulations linked to neuropsychiatric diseases may potentially assist the diagnosis of these disorders. Most of these biomarkers are found in the brain tissue, which is not easily accessible. This is the challenge for the search of novel biomarkers that are present in various body fluids, including serum or plasma. As a group of important endogenous small noncoding RNAs that regulate gene expression at post-transcriptional level, microRNAs (miRNAs play a crucial role in many physiological and pathological processes. Previously, researchers discovered that miRNAs contribute to the neurodevelopment and maturation, including neurite outgrowth, dendritogenesis and dendritic spine formation. These developments underline the significance of miRNAs as potential biomarkers for diagnosing and prognosing central nervous system diseases. Accumulated evidence indicates that there are considerable differences between the cell-free miRNA expression profiles of healthy subjects and those of patients. Therefore, circulating miRNAs are likely to become a new class of noninvasive, sensitive biomarkers. Despite the fact that little is known about the origin and functions of circulating miRNAs, their essential roles in the clinical diagnosis and prognosis of neuropsychiatric diseases make them attractive biomarkers. In this review we cover the increasing amounts of dataset that have accumulated in the last years on the use of circulating miRNAs and their values as potential biomarkers in most areas of neuropsychiatric diseases.

  8. Mycoplasma hyopneumoniae type I signal peptidase: expression and evaluation of its diagnostic potential.

    Science.gov (United States)

    Moitinho-Silva, Lucas; Heineck, Bianca L; Reolon, Luciano A; Paes, Jéssica A; Klein, Cátia S; Rebelatto, Raquel; Schrank, Irene S; Zaha, Arnaldo; Ferreira, Henrique B

    2012-01-27

    Type I signal peptidase (SPase I) is a membrane-anchored protease of the general secretory pathway, which is encoded by the sipS gene in Mycoplasma hyopneumoniae, the etiological agent of porcine enzootic pneumonia (PEP). In this study, the expression of the M. hyopneumoniae SPase I (MhSPase I) was analyzed in virulent and avirulent strains, and the recombinant protein (rMhSPase I), expressed in Escherichia coli, was evaluated regarding its potential as an immunodiagnostic antigen. It was demonstrated that the sipS coding DNA sequence (CDS) is most likely part of an operon, being co-transcribed along with four other CDSs. Quantitative reverse transcriptase PCR and immunoblot assays showed that MhSPase I is expressed by all three strains analyzed, with no transcriptional difference, but with evidence of a higher protein level in a pathogenic strain (7422), in comparison to another pathogenic (7448) and a non-pathogenic (J) strain. rMhSPase I was strongly immunogenic for mice, and the MhSPase I antigenicity was confirmed. Polyclonal serum anti-rMhSPase I presented no detectable cross-reaction with Mycoplasma flocculare and Mycoplasma hyorhinis. Moreover, phylogenetic analysis demonstrated a low conservation between MhSPase I and orthologous proteins from other porcine respiratory disease complex-related bacteria, Firmicutes and other Mycoplasma species. The potential of an rMhSPase I-based ELISA for PEP immunodiagnosis was demonstrated. Overall, we investigated the expression of sipS and the encoded MhSPase I in three M. hyopneumoniae strains and showed that this protein is a good antigen for use in PEP serodiagnosis and possibly vaccination, as well as a potential target for antibiotic development. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Large protein as a potential target for use in rabies diagnostics.

    Science.gov (United States)

    Santos Katz, I S; Dias, M H; Lima, I F; Chaves, L B; Ribeiro, O G; Scheffer, K C; Iwai, L K

    Rabies is a zoonotic viral disease that remains a serious threat to public health worldwide. The rabies lyssavirus (RABV) genome encodes five structural proteins, multifunctional and significant for pathogenicity. The large protein (L) presents well-conserved genomic regions, which may be a good alternative to generate informative datasets for development of new methods for rabies diagnosis. This paper describes the development of a technique for the identification of L protein in several RABV strains from different hosts, demonstrating that MS-based proteomics is a potential method for antigen identification and a good alternative for rabies diagnosis.

  10. Benefits of a European project on diagnostics of highly pathogenic agents and assessment of potential "dual use" issues.

    Science.gov (United States)

    Grunow, Roland; Ippolito, G; Jacob, D; Sauer, U; Rohleder, A; Di Caro, A; Iacovino, R

    2014-01-01

    Quality assurance exercises and networking on the detection of highly infectious pathogens (QUANDHIP) is a joint action initiative set up in 2011 that has successfully unified the primary objectives of the European Network on Highly Pathogenic Bacteria (ENHPB) and of P4-laboratories (ENP4-Lab) both of which aimed to improve the efficiency, effectiveness, and response capabilities of laboratories directed at protecting the health of European citizens against high consequence bacteria and viruses of significant public health concern. Both networks have established a common collaborative consortium of 37 nationally and internationally recognized institutions with laboratory facilities from 22 European countries. The specific objectives and achievements include the initiation and establishment of a recognized and acceptable quality assurance scheme, including practical external quality assurance exercises, comprising living agents, that aims to improve laboratory performance, accuracy, and detection capabilities in support of patient management and public health responses; recognized training schemes for diagnostics and handling of highly pathogenic agents; international repositories comprising highly pathogenic bacteria and viruses for the development of standardized reference material; a standardized and transparent Biosafety and Biosecurity strategy protecting healthcare personnel and the community in dealing with high consequence pathogens; the design and organization of response capabilities dealing with cross-border events with highly infectious pathogens including the consideration of diagnostic capabilities of individual European laboratories. The project tackled several sensitive issues regarding Biosafety, Biosecurity and "dual use" concerns. The article will give an overview of the project outcomes and discuss the assessment of potential "dual use" issues.

  11. The potential of high resolution melting analysis (hrma) to streamline, facilitate and enrich routine diagnostics in medical microbiology.

    Science.gov (United States)

    Ruskova, Lenka; Raclavsky, Vladislav

    2011-09-01

    Routine medical microbiology diagnostics relies on conventional cultivation followed by phenotypic techniques for identification of pathogenic bacteria and fungi. This is not only due to tradition and economy but also because it provides pure culture needed for antibiotic susceptibility testing. This review focuses on the potential of High Resolution Melting Analysis (HRMA) of double-stranded DNA for future routine medical microbiology. Search of MEDLINE database for publications showing the advantages of HRMA in routine medical microbiology for identification, strain typing and further characterization of pathogenic bacteria and fungi in particular. The results show increasing numbers of newly-developed and more tailor-made assays in this field. For microbiologists unfamiliar with technical aspects of HRMA, we also provide insight into the technique from the perspective of microbial characterization. We can anticipate that the routine availability of HRMA in medical microbiology laboratories will provide a strong stimulus to this field. This is already envisioned by the growing number of medical microbiology applications published recently. The speed, power, convenience and cost effectiveness of this technology virtually predestine that it will advance genetic characterization of microbes and streamline, facilitate and enrich diagnostics in routine medical microbiology without interfering with the proven advantages of conventional cultivation.

  12. Outer Membrane Protein A Conservation among Orientia tsutsugamushi Isolates Suggests Its Potential as a Protective Antigen and Diagnostic Target

    Directory of Open Access Journals (Sweden)

    Sean M. Evans

    2018-06-01

    Full Text Available Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially-available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically-related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs and blood of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly-protective scrub typhus vaccine.

  13. PATIENTS WITH SUSPECTED METAL IMPLANT ALLERGY: POTENTIAL CLINICAL PICTURES AND ALLERGOLOGICAL DIAGNOSTIC APPROACH (REVIEW

    Directory of Open Access Journals (Sweden)

    P. Thomas

    2014-01-01

    Full Text Available The focus of this review are allergic complications following insertion of metallic orthopedic implants. Such potential allergic reactions encompass eczema, impaired wound and fracture healing, infection-mimicking reactions, effusions, pain and loosening. Nickel, cobalt and chromium seem to be the predominant eliciting allergens. Allergy might be considered prior to planned orthopaedic surgery or in patients with complications following arthroplasty We recommend, that differential diagnoses - in particular infection -should always be excluded in cooperation with surgery collegues. The clinical work up of a patient suspected of suffering from metal implant allergy should include a combined evaluation of medical history, clinical findings, patch testing and histology In vitro testing, namely the lymphocyte transformation test (LTT, can indicate metal sensitization, but needs careful interpretation.

  14. PRESSURE EFFECTS IN POLYCYCLIC AROMATIC NITROGENATED HETEROCYCLES (PANHs): DIAGNOSTIC QUALITIES AND COSMOBAROMETRY POTENTIAL

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, Wren; Sephton, Mark A., E-mail: w.montgomery@imperial.ac.uk [Impacts and Astromaterials Research Centre, Department of Earth Science and Engineering, Imperial College London SW7 2AZ (United Kingdom)

    2016-03-01

    The influence of polycyclic aromatic nitrogen heterocycles (PANHs), which have been suggested as contributors to the interstellar IR emission bands, on interstellar emission features is difficult to constrain because their infrared characteristics are strongly similar to those for polycyclic aromatic hydrocarbons (PAHs). One possible solution is to seek a means of visualizing the presence of PANHs that provides information that is distinct from that for PAHs. Although PANHs and PAHs have similar infrared characteristics in many settings, this relationship may not be universally maintained. We have used in situ high-pressure synchrotron-source Fourier transform infrared spectroscopy to determine that the responses of two representative molecules, acridine and anthracene, differ at high pressures (>ca. 1 GPa). Because there are a number of high-pressure environments that can be remotely observed by infrared spectroscopy, they represent a potential to glimpse the distribution of PANHs across the cosmos.

  15. Rib biomechanical properties exhibit diagnostic potential for accurate ageing in forensic investigations

    Science.gov (United States)

    Bonicelli, Andrea; Xhemali, Bledar; Kranioti, Elena F.

    2017-01-01

    Age estimation remains one of the most challenging tasks in forensic practice when establishing a biological profile of unknown skeletonised remains. Morphological methods based on developmental markers of bones can provide accurate age estimates at a young age, but become highly unreliable for ages over 35 when all developmental markers disappear. This study explores the changes in the biomechanical properties of bone tissue and matrix, which continue to change with age even after skeletal maturity, and their potential value for age estimation. As a proof of concept we investigated the relationship of 28 variables at the macroscopic and microscopic level in rib autopsy samples from 24 individuals. Stepwise regression analysis produced a number of equations one of which with seven variables showed an R2 = 0.949; a mean residual error of 2.13 yrs ±0.4 (SD) and a maximum residual error value of 2.88 yrs. For forensic purposes, by using only bench top machines in tests which can be carried out within 36 hrs, a set of just 3 variables produced an equation with an R2 = 0.902 a mean residual error of 3.38 yrs ±2.6 (SD) and a maximum observed residual error 9.26yrs. This method outstrips all existing age-at-death methods based on ribs, thus providing a novel lab based accurate tool in the forensic investigation of human remains. The present application is optimised for fresh (uncompromised by taphonomic conditions) remains, but the potential of the principle and method is vast once the trends of the biomechanical variables are established for other environmental conditions and circumstances. PMID:28520764

  16. State of consciousness and ERP (event-related potential measures. Diagnostic and prognostic value of electrophysiology for disorders of consciousness

    Directory of Open Access Journals (Sweden)

    Michela Balconi

    2011-11-01

    Full Text Available Disorders of consciousness were amply studied in the recent years. At this regards new methodologies and technologies were applied to explore the diagnostic and prognostic criteria that may be applied to the patients. Specifically electrophysiological measures were used to verify the degree of awareness and responsiveness in coma, vegetative states (VS, minimal consciousness state (MC, and locked-in syndrome (LI. Recently, ERPs (event-related potentials were adopted to integrate the classical neuroimaging measures. Between the others, MMN (mismatch negativity and P300 deflections were found to represent a consistent index of the present state of consciousness and to be predictive of successive modifications of this state. Also frequency-based EEG measures, such as brain oscillations, were revealed to be relevant marker of consciousness and awareness, able to predict the future evolution of pathology.

  17. Pathogenic and Diagnostic Potential of BLCA-1 and BLCA-4 Nuclear Proteins in Urothelial Cell Carcinoma of Human Bladder

    Directory of Open Access Journals (Sweden)

    Matteo Santoni

    2012-01-01

    Full Text Available Transitional cell carcinoma (TCC of the bladder is one of the most common malignancies of genitourinary tract. Patients with bladder cancer need a life-long surveillance, directly due to the relatively high recurrence rate of this tumor. The use of cystoscopy represents the gold standard for the followup of previously treated patients. Nevertheless, several factors, including cost and invasiveness, render cystoscopy not ideal for routine controls. Advances in the identification of specific alterations in the nuclear structure of bladder cancer cells have opened novel diagnostic landscapes. The members of nuclear matrix protein family BLCA-1 and BLCA-4, are currently under evaluation as bladder cancer urinary markers. They are involved in tumour cell proliferation, survival, and angiogenesis. In this paper, we illustrate the role of BLCA-1 and BLCA-4 in bladder carcinogenesis and their potential exploitation as biomarkers in this cancer.

  18. Invasion-Related Factors as Potential Diagnostic and Therapeutic Targets in Oral Squamous Cell Carcinoma—A Review

    Science.gov (United States)

    Siriwardena, Samadarani B. S. M.; Tsunematsu, Takaaki; Qi, Guangying; Ishimaru, Naozumi; Kudo, Yasusei

    2018-01-01

    It is well recognized that the presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). In solid epithelial cancer, the first step during the process of metastasis is the invasion of cancer cells into the underlying stroma, breaching the basement membrane (BM)—the natural barrier between epithelium and the underlying extracellular matrix (ECM). The ability to invade and metastasize is a key hallmark of cancer progression, and the most complicated and least understood. These topics continue to be very active fields of cancer research. A number of processes, factors, and signaling pathways are involved in regulating invasion and metastasis. However, appropriate clinical trials for anti-cancer drugs targeting the invasion of OSCC are incomplete. In this review, we summarize the recent progress on invasion-related factors and emerging molecular determinants which can be used as potential for diagnostic and therapeutic targets in OSCC. PMID:29758011

  19. Molecular methods for pathogen and microbial community detection and characterization: current and potential application in diagnostic microbiology.

    Science.gov (United States)

    Sibley, Christopher D; Peirano, Gisele; Church, Deirdre L

    2012-04-01

    Clinical microbiology laboratories worldwide have historically relied on phenotypic methods (i.e., culture and biochemical tests) for detection, identification and characterization of virulence traits (e.g., antibiotic resistance genes, toxins) of human pathogens. However, limitations to implementation of molecular methods for human infectious diseases testing are being rapidly overcome allowing for the clinical evaluation and implementation of diverse technologies with expanding diagnostic capabilities. The advantages and limitation of molecular techniques including real-time polymerase chain reaction, partial or whole genome sequencing, molecular typing, microarrays, broad-range PCR and multiplexing will be discussed. Finally, terminal restriction fragment length polymorphism (T-RFLP) and deep sequencing are introduced as technologies at the clinical interface with the potential to dramatically enhance our ability to diagnose infectious diseases and better define the epidemiology and microbial ecology of a wide range of complex infections. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. The diagnostic value of endothelial function as a potential sensor of fatigue in health

    Directory of Open Access Journals (Sweden)

    Yoshiko Ohno

    2010-03-01

    Full Text Available Yoshiko Ohno1,2, Teruto Hashiguchi1, Ryuichi Maenosono1, Hidetoshi Yamashita3, Yukio Taira3, Kazufumi Minowa3, Yoshihito Yamashita3, Yuko Kato3, Ko-ichi Kawahara1, Ikuro Maruyama11Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima City, Kagoshima Prefecture, Japan; 2Department of Community Health Nursing/Nursing Informatics, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima City, Kagoshima Prefecture, Japan; 3Kagoshima Seikyo General Hospital, Kagoshima City, Kagoshima Prefecture, JapanPurpose: Many epidemiological research studies have shown that vital exhaustion and psychosocial factors are associated with the occurrence of cerebrocardiovascular disease (CCVD. Fatigue is thought to induce endothelial dysfunction and may be linked to the occurrence of CCVD; however, no studies have investigated this potential link. We studied to determine the effect of fatigue on endothelial function in healthy subjects with no traditional CCVD risk factors or potential confounding factors to be controlled.Subjects and methods: Peripheral arterial tonometry (PAT was used to evaluate endothelial function. The influence of the following parameters on endothelial function was analyzed in 74 office workers without traditional CCVD risk factors at health check-ups: endothelial function before and after work, subjective fatigue, lifestyle factors such as sleeping time, and psychosocial factors such as depression and social support.Results: Twenty-five subjects (33.8% had low endothelial function; reactive hyperemia (RH-PAT index <1.67, even though no abnormalities were reported in the health check-ups. There was no significant difference in endothelial function before versus after labor. Of note, endothelial function was associated with the individual’s level of subjective fatigue (t = 2.98, P = 0.008 and showed a daily fluctuation, sometimes to a pathological

  1. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

    Czech Academy of Sciences Publication Activity Database

    Králová, Alena; Světlíková, M.; Madar, J.; Ulčová-Gallová, Z.; Bukovský, A.; Pěknicová, Jana

    2008-01-01

    Roč. 6, č. 27 (2008), s. 1-16 ISSN 1477-7827 R&D Projects: GA MŠk OE 211 Institutional research plan: CEZ:AV0Z50520701 Keywords : transferrin * monoclonal antibody * human placentae Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.634, year: 2008

  2. Transferrin Family Genes in the Brown Planthopper, Nilaparvata lugens (Hemiptera: Delphacidae) in Response to Three Insecticides.

    Science.gov (United States)

    Wu, Shun-Fan; Li, Jian; Zhang, Yong; Gao, Cong-Fen

    2018-02-09

    Transferrins are involved in iron metabolism, immunity, xenobiotics tolerance, and development in eukaryotic organisms including insects. However, little is known about the relationship between transferrins and insecticide toxicology and resistance. Three transferrin family genes, NlTsf1, NlTsf2, and NlTsf3, of the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae)a major insect pest of rice field in Asia, had been identified and characterized in this study. Quantitative polymerase chain reaction results demonstrated that NlTsf1 was significantly higher than the other two genes in different tissues. All of them were expressed at higher levels in abdomen and head than in antenna, leg, stylet, and thorax. Compared with the control, the expression of three N. lugens transferrin family genes decreased dramatically 24 h after treatment with buprofezin, pymetrozine and imidacloprid. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  3. Transferrin receptor-1 and ferritin heavy and light chains in astrocytic brain tumors

    DEFF Research Database (Denmark)

    Rosager, Ann Mari; Sørensen, Mia D; Dahlrot, Rikke H

    2017-01-01

    Astrocytic brain tumors are the most frequent primary brain tumors. Treatment with radio- and chemotherapy has increased survival making prognostic biomarkers increasingly important. The aim of the present study was to investigate the expression and prognostic value of transferrin receptor-1 (TfR...

  4. The influence of maternal smoking on transferrin sialylation and fetal biometric parameters.

    Science.gov (United States)

    Wrześniak, Marta; Królik, Małgorzata; Kepinska, Marta; Milnerowicz, Halina

    2016-10-01

    Transferrin is a glycosylated protein responsible for transporting iron, an essential metal responsible for proper fetal development. Tobacco is a heavily used xenobiotic having a negative impact on the human body and pregnancy outcomes. Aims of this study was to examine the influence of tobacco smoking on transferrin sialic acid residues and their connection with fetal biometric parameters in women with iron-deficiency. The study involved 173 samples from pregnant women, smokers and non-smokers, iron deficient and not. Transferrin sialylation was determined by capillary electrophoresis. The cadmium (Cd) level was measured by atomic absorption and the sialic acid concentration by the resorcinol method. Women with iron deficiencies who smoked gave birth earlier than non-smoking, non-iron-deficient women. The Cd level, but not the cotinine level, was positively correlated with transferrin sialylation in the blood of iron-deficient women who smoked; 3-, 4-, 5- and 6-sialoTf correlated negatively with fetal biometric parameters in the same group. It has been shown the relationship between Cd from tobacco smoking and fetal biometric parameters observed only in the iron deficient group suggests an additive effect of these two factors, and indicate that mothers with anemia may be more susceptible to Cd toxicity and disturbed fetal development. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Diagnostic criteria of well differentiated thyroid tumor of uncertain malignant potential; a histomorphological and immunohistochemical appraisal.

    Science.gov (United States)

    Yassin, Fatma El-Zahraa Salah El-Deen

    2015-06-01

    Well differentiated thyroid tumor of uncertain malignant potential (WDT-UMP) represents a true "gray zone" of "follicular patterned" thyroid lesions, that needs to be characterized in order to outright the diagnosis of carcinoma and avoid unnecessary aggressive treatment. To emphasize on the histomorphological criteria for more accurate diagnosis of WDT-UMP. Also to compare the immunohistochemical expression of CK19 of WDT-UMP versus adenoma and papillary thyroid carcinoma (PTC). The study included 60 thyroid specimens; 18 WDT-UMPs, 24 PTC (18 classic variant and 6 follicular variants) and 18 benign thyroid lesions (8 adenoma, 6 Hashimoto's thyroiditis and 4 hyperplastic nodules). H&E stained sections were assessed according to the published major and minor criteria of malignancy in the thyroid. CK 19 immunostaining was examined and evaluated according to the proportion and intensity scores. We could detect the absence of nuclear inclusions, presence of characteristic nuclear groove, nuclear clearing, ovoid nuclei, nuclear crowdness, nuclear enlargement and pleomorphism as important reliable features for diagnosis of WDT-UMP with p value (<0.0001 for each). WDT-UMP showed moderate to strong CK 19 immunostaining with proportion scores 3 and 4; an intermediate expression profile; higher than adenoma and less than papillary carcinoma (p<0.0001). The constellations of both major and minor criteria of malignancy are important clues for WDT-UMP diagnosis which could be ascertained by CK 19 immunostaining. Copyright © 2015. Production and hosting by Elsevier B.V.

  6. Molecular diagnostics on the toxigenic potential of Fusarium spp. plant pathogens.

    Science.gov (United States)

    Dawidziuk, A; Koczyk, G; Popiel, D; Kaczmarek, J; Buśko, M

    2014-06-01

    We propose and test an efficient and rapid protocol for the detection of toxigenic Fusarium isolates producing three main types of Fusarium-associated mycotoxins (fumonisins, trichothecenes and zearelanone). The novel approach utilizes partially multiplexed markers based on genes essential for mycotoxin biosynthesis (fumonisin--fum6, fum8; trichothecenes--tri5, tri6; zearalenone, zea2) in Fusarium spp. The protocol has been verified by screening a collection of 96 isolates representing diverse species of filamentous fungi. Each Fusarium isolate was taxonomically identified through both molecular and morphological techniques. The results demonstrate a reliable detection of toxigenic potential for trichothecenes (sensitivity 100%, specificity 95%), zearalenone (sensitivity 100%, specificity 100%) and fumonisins (sensitivity 94%, specificity 88%). Both presence and identity of toxin biosynthetic genes were further confirmed by direct sequencing of amplification products. The cross-species-specific PCR markers for key biosynthetic genes provide a sensitive detection of toxigenic fungal isolates, contaminating biological material derived from agricultural fields. The conducted study shows that a PCR-based assay of biosynthetic genes is a reliable, cost-effective, early warning system against Fusarium contamination. Its future use as a high-throughput detection strategy complementing chemical assays enables effective targeted application of crop protection products. © 2014 The Authors. published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.

  7. Realising the Potential of Urine and Saliva as Diagnostic Tools in Sport and Exercise Medicine.

    Science.gov (United States)

    Lindsay, Angus; Costello, Joseph T

    2017-01-01

    Accurate monitoring of homeostatic perturbations following various psychophysiological stressors is essential in sports and exercise medicine. Various biomarkers are routinely used as monitoring tools in both clinical and elite sport settings. Blood collection and muscle biopsies, both invasive in nature, are considered the gold standard for the analysis of these biomarkers in exercise science. Exploring non-invasive methods of collecting and analysing biomarkers that are capable of providing accurate information regarding exercise-induced physiological and psychological stress is of obvious practical importance. This review describes the potential benefits, and the limitations, of using saliva and urine to ascertain biomarkers capable of identifying important stressors that are routinely encountered before, during, or after intense or unaccustomed exercise, competition, over-training, and inappropriate recovery. In particular, we focus on urinary and saliva biomarkers that have previously been used to monitor muscle damage, inflammation, cardiovascular stress, oxidative stress, hydration status, and brain distress. Evidence is provided from a range of empirical studies suggesting that urine and saliva are both capable of identifying various stressors. Although additional research regarding the efficacy of using urine and/or saliva to indicate the severity of exercise-induced psychophysiological stress is required, it is likely that these non-invasive biomarkers will represent "the future" in sports and exercise medicine.

  8. Screening of Oral Potentially Malignant Disorders Using Exfoliative Cytology: A Diagnostic Modality

    International Nuclear Information System (INIS)

    Kabiraj, A.

    2016-01-01

    Oral exfoliative cytology (OEC) has been implemented in the diagnosis of pathologic lesions for ages. The present study was undertaken to evaluate the cytomorphological features of some of the commonest potentially malignant disorders (leukoplakia, lichen planus, and oral sub mucous fibrosis) through a simple procedure and illustrate its importance in mass screening. Materials and Method. A total of 160 subjects with 25-50 years of age were included in the study. Among them, 40 were clinically diagnosed with oral leukoplakia, 40 were diagnosed with oral lichen planus, 40 were diagnosed with oral sub mucous fibrosis, and 40 were in the control group. The prepared smears were subjected to Papanicolaou stain and analyzed microscopically for the evaluation of the cytomorphological features. Results and Discussion. When analyzed microscopically, 36 (90%) out of the 40 oral leukoplakic lesions showed Class II cytological features whereas 4 (10%) revealed Class I features. Among 40 patients with oral lichen planus, 26 (65%) showed Class II features while the remaining 14 (35%) revealed Class I features. In 40 subjects with oral sub mucous fibrosis, 32 (80%) showed Class II features while the other 8 (20%) showed Class I features. All the 40 control subjects showed Class I features. Thus, OEC can be widely advocated as an addition to clinical conclusion and an adjunct to biopsy.

  9. Recurrent Mastoiditis Mimics IgG4 Related Disease: A Potential Diagnostic Pitfall.

    Science.gov (United States)

    Deshpande, Vikram; Zane, Nicolas A; Kraft, Stefan; Stone, John H; Faquin, William C

    2016-09-01

    IgG4-related disease (IgG4-RD) is a recently recognized entity that causes progressive fibrosis and formation of mass lesions. IgG4-RD can be diagnosed histologically by its hallmarks of storiform fibrosis, prominent lymphoplasmacytic infiltrate, and obliterative phlebitis, accompanied by the infiltration of excessive numbers of IgG4-positive plasma cells as well as elevations in serum IgG4 concentrations. A recent publication reported a case of IgG4-RD in the mastoid sinus, representing a new anatomic location for this disease. We report two additional cases of IgG4-RD occurring in the mastoid and causing clinical mastoiditis. The presenting symptoms were varied-tinnitus, hearing loss, and cranial nerve palsies. All three cases showed a dense lymphoplasmacytic infiltrate, storiform type fibrosis as well as elevated numbers of IgG4 positive plasma cells. The three patients responded to immunosuppressive therapy that included steroids and Rituximab. We further investigated 162 consecutive mastoiditis cases at our institution in order to determine the frequency of IgG4-RD as a previously unrecognized cause of mastoiditis. Within this latter cohort we identified nine cases of mastoiditis that had two of the histologic features of IgG4-RD, specifically storiform fibrosis and a dense lymphoplasmacytic infiltrate. Two of these cases showed >50 IgG4-positive plasma cells per high-power field with IgG4-IgG ratio of >40 %, thus fulfilling histological criteria for IgG4-RD. However, both were due to severe acute or chronic infection. In conclusion, we reaffirm IgG4 related mastoiditis as a distinct but uncommon cause of recurrent mastoiditis. The diagnosis of IgG4-related mastoiditis should be rendered with caution, and only after the exclusion of potential mimickers, particularly infection.

  10. Soluble transferrin receptor as a marker of erythropoiesis in patients undergoing high-flux hemodialysis

    Directory of Open Access Journals (Sweden)

    Pei Yin

    2017-11-01

    Full Text Available Anemia is a common complication in chronic kidney disease (CKD patients receiving hemodialysis. The effect of high-flux dialysis (HFD on anemia remains unclear. This prospective study aimed to evaluate the effect of HFD on anemia, and the potential of soluble transferrin receptor (sTfR as a marker of iron status and erythropoiesis in CKD patients on hemodialysis. Forty patients, who switched from conventional low-flux dialysis to HFD for 12 months, were enrolled in this study. The levels of sTfR, hemoglobin (Hb, iron, and nutritional markers, as well as the dose of recombinant human erythropoietin (rhEPO and use of chalybeate were determined at 0, 2, 6, and 12 months after starting HFD. HFD significantly increased the hemoglobin level and reduced sTfR level in CKD patients (p < 0.05. In addition, significant decreasing linear trends were observed for rhEPO dosage and chalybeate use (p < 0.05. The level of sTfR was positively correlated with the percentage of reticulocytes (RET%, rhEPO dose, and chalybeate use, while it was negatively correlated with Hb levels and total iron-binding capacity results (all p < 0.05. A univariate generalized estimating equation (GEE model showed that the Hb level, RET%, rhEPO dose, and chalybeate use were the variables associated with sTfR levels. A multivariate GEE model showed that the time points when hemodialysis was performed were the variables associated significantly with sTfR levels. Overall, our findings suggest that HFD can effectively improve renal anemia in hemodialysis patients, and sTfR could be used as a marker of erythropoiesis in HFD patients.

  11. Role of Insulin-Transferrin-Selenium in Auricular Chondrocyte Proliferation and Engineered Cartilage Formation in Vitro

    Directory of Open Access Journals (Sweden)

    Xia Liu

    2014-01-01

    Full Text Available The goal of this study is to determine the effects of Insulin-Transferrin-Selenium (ITS on proliferation of auricular chondrocytes and formation of engineered cartilage in vitro. Pig auricular monolayer chondrocytes and chondrocyte pellets were cultured in media containing 1% ITS at different concentrations of fetal bovine serum (FBS, 10%, 6%, 2%, 0%, or 10% FBS alone as a control for four weeks. Parameters including cell proliferation in monolayer, wet weight, collagen type I/II/X (Col I, II, X and glycosaminoglycan (GAG expression, GAG content of pellets and gene expression associated with cartilage formation/dedifferentiation (lost cartilage phenotype/hypertrophy within the chondrocyte pellets were assessed. The results showed that chondrocytes proliferation rates increased when FBS concentrations increased (2%, 6%, 10% FBS in ITS supplemented groups. In addition, 1% ITS plus 10% FBS significantly promoted cell proliferation than 10% FBS alone. No chondrocytes grew in ITS alone medium. 1% ITS plus 10% FBS enhanced cartilage formation in terms of size, wet weight, cartilage specific matrices, and homogeneity, compared to 10% FBS alone group. Furthermore, ITS prevented engineered cartilage from dedifferentiation (i.e., higher index of Col II/Col I mRNA expression and expression of aggrecan and hypertrophy (i.e., lower mRNA expression of Col X and MMP13. In conclusion, our results indicated that ITS efficiently enhanced auricular chondrocytes proliferation, retained chondrogenic phenotypes, and promoted engineered cartilage formation when combined with FBS, which is potentially used as key supplementation in auricular chondrocytes and engineered cartilage culture.

  12. MicroRNA-367 is a potential diagnostic biomarker for patients with esophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jiangtao; Song, Kaifang; Feng, Xiaoshan, E-mail: xiaoshan.feng@aol.com; Gao, Shegan

    2016-04-29

    Purpose: In this study, we investigated whether microRNA-367 (miR-367) may serve as a circulating biomarker and tumor oncogene in esophageal squamous carcinoma (ESCC). Methods: Circulating serum miR-367 was compared by quantitative RT-PCR (qRT-PCR) between 35 ESCC patients and 35 normal control patients, as well paired ESCC tumor tissues and adjacent non-tumor esophageal epithelial tissues in 46 patients. The correlation between serum miR-367 and clinicopathological properties of ESCC patients was assessed. The overall survival (OS) was assessed by Kaplan–Meier method and compared by log-rank test between patients with high serum miR-367 and low serum miR-367. The possibility of miR-367 being independent prognostic factor for ESCC was also assessed. Furthermore, lentivirus-mediated miR-367 downregulation was conducted in ESCC cell lines Kyse30 and TE-1 cells to assess the possible oncogenic effect of miR-367 on ESCC proliferation and cell cycle transition in vitro. Results: MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients, whereas downregulated in ESCC patients after the treatments of esophagectomy and chemotherapy. Serum miR-367 was found to be closely correlated with the clinicopathological properties of differentiation grades, clinical stage and tumor metastasis in ESCC patients. Serum miR-367 was also confirmed to be associated with OS, as well as serving independent prognostic factor in ESCC patients. Moreover, lentivirus-induced miR-367 downregulation inhibited cancer growth and cell cycle transition in Kyse30 and TE-1 cells. Conclusion: MiR-367 is a potential biomarker for ESCC and may act as an oncogene in regulating ESCC development. - Highlights: • MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients. • MiR-367 was downregulated in ESCC patients after esophagectomy or chemotherapy. • Serum miR-367 was correlated with the clinicopathological properties of ESCC patients. • Serum miR-367 was associated

  13. Diagnostic yield of hair and urine toxicology testing in potential child abuse cases.

    Science.gov (United States)

    Stauffer, Stephanie L; Wood, Stephanie M; Krasowski, Matthew D

    2015-07-01

    Detection of drugs in a child may be the first objective finding that can be reported in cases of suspected child abuse. Hair and urine toxicology testing, when performed as part of the initial clinical evaluation for suspected child abuse or maltreatment, may serve to facilitate the identification of at-risk children. Furthermore, significant environmental exposure to a drug (considered by law to constitute child abuse in some states) may be identified by toxicology testing of unwashed hair specimens. In order to determine the clinical utility of hair and urine toxicology testing in this population we performed a retrospective chart review on all children for whom hair toxicology testing was ordered at our academic medical center between January 2004 and April 2014. The medical records of 616 children aged 0-17.5 years were reviewed for injury history, previous medication and illicit drug use by caregiver(s), urine drug screen result (if performed), hair toxicology result, medication list, and outcome of any child abuse evaluation. Hair toxicology testing was positive for at least one compound in 106 cases (17.2%), with unexplained drugs in 82 cases (13.3%). Of these, there were 48 cases in which multiple compounds (including combination of parent drugs and/or metabolites within the same drug class) were identified in the sample of one patient. The compounds most frequently identified in the hair of our study population included cocaine, benzoylecgonine, native (unmetabolized) tetrahydrocannabinol, and methamphetamine. There were 68 instances in which a parent drug was identified in the hair without any of its potential metabolites, suggesting environmental exposure. Among the 82 cases in which hair toxicology testing was positive for unexplained drugs, a change in clinical outcome was noted in 71 cases (86.5%). Urine drug screens (UDS) were performed in 457 of the 616 reviewed cases. Of these, over 95% of positive UDS results could be explained by iatrogenic drug

  14. Benefits of a European Project on Diagnostics of Highly Pathogenic Agents and Assessment of Potential “Dual Use” Issues

    Science.gov (United States)

    Grunow, Roland; Ippolito, G.; Jacob, D.; Sauer, U.; Rohleder, A.; Di Caro, A.; Iacovino, R.

    2014-01-01

    Quality assurance exercises and networking on the detection of highly infectious pathogens (QUANDHIP) is a joint action initiative set up in 2011 that has successfully unified the primary objectives of the European Network on Highly Pathogenic Bacteria (ENHPB) and of P4-laboratories (ENP4-Lab) both of which aimed to improve the efficiency, effectiveness, and response capabilities of laboratories directed at protecting the health of European citizens against high consequence bacteria and viruses of significant public health concern. Both networks have established a common collaborative consortium of 37 nationally and internationally recognized institutions with laboratory facilities from 22 European countries. The specific objectives and achievements include the initiation and establishment of a recognized and acceptable quality assurance scheme, including practical external quality assurance exercises, comprising living agents, that aims to improve laboratory performance, accuracy, and detection capabilities in support of patient management and public health responses; recognized training schemes for diagnostics and handling of highly pathogenic agents; international repositories comprising highly pathogenic bacteria and viruses for the development of standardized reference material; a standardized and transparent Biosafety and Biosecurity strategy protecting healthcare personnel and the community in dealing with high consequence pathogens; the design and organization of response capabilities dealing with cross-border events with highly infectious pathogens including the consideration of diagnostic capabilities of individual European laboratories. The project tackled several sensitive issues regarding Biosafety, Biosecurity and “dual use” concerns. The article will give an overview of the project outcomes and discuss the assessment of potential “dual use” issues. PMID:25426479

  15. Detection of Potentially Diagnostic Leishmania Antigens with Western Blot Analysis of Sera from Patients with Cutaneous and Visceral Leishmaniases

    Directory of Open Access Journals (Sweden)

    Seyyed Javad SEYYEDTABAEI

    2017-06-01

    Full Text Available Background: Visceral leishmaniasis (VL and cutaneous leishmaniasis (CL are important public health problems in Iran. We aimed to evaluate the diagnostic potential of Western blot (WB compared with indirect immunofluorescence test (IFAT to serodiagnosis of leishmaniasis.Methods: This study was performed from 2010-2014 and participants were different parts of Iran. Serum samples were obtained from 43 patients with proven CL, 33 patients with proven VL, 39 patients with other parasitic diseases and 23 healthy individuals. Results: WB sensitivity for CL and VL was 100% and 91%, compared to IFA 4.6% and 87.8%, respectively. Sera from patients with CL and VL recognized numerous antigens with molecular weights ranging from 14 to 68 kDa and 12 to 94 kDa, respectively. The most sensitive antigens were 14 and 16 kDa for CL recognized by 100% of the sera from patients with proven CL and 12, 14 and 16 kDa for VL, recognized by 63.6%, 100% and 63.6% of the sera from patients with proven VL respectively. WB analysis is more sensitive than IFAT for the diagnosis of leishmaniasis particularly in cases of cutaneous leishmaniasis. The 12, 14 and 16 kDa can be valuable diagnostic molecules for serodiagnosis of leishmaniasis because at least two immunogenic molecules were simultaneously detected by all patient sera, as well as produced antibodies against these antigens have no cross-reactivity with other control groups.Conclusion: WB could be useful for screening and serodiagnosis of CL and VL in epidemiologic studies in endemic areas.

  16. New trends in radioisotope renal function studies: Improved diagnostic potential by pharmacological intervention and by quantitative analysis

    International Nuclear Information System (INIS)

    Kletter, K.

    1988-01-01

    Tc99m mercaptoacetyltriglycine (Tc99m MAG3) was tested as replacement for I123 orthoiodohippuric acid (I123 oIH) both in the form of a HPLC purified substance and as an impure kit preparation. The influence of angiotensin converting enzyme (ACE) inhibitors (captopril) leads to characteristic changes in the renograms of patients with Goldblatt hypertension. Quantitative criteria for the evidence of haemodynamically significant renal artery stenosis were derived from investigations without and with captopril (25 mg) (I123 oIH and Tc99m DTPA) in 21 patients with essential hypertension. Diuresis renography is used for the assessment of urinary outflow obstruction. Up till now mainly qualitative criteria have been used for the evaluation of the washout curves. The introduction of the quantitative parameter of peak elimination rate for washout curve analysis yielded a significantly better concordance between diuresis renography and the invasive Whitaker test. The parameter of peak elimination (E max ) is mathematically clearly defined and is closely related to the peak urinary flow after frusemide. The dependence of the diuresis renogram on renal function and the degree of hydronephrosis was investigated in 80 ureterorenal units. Diuresis renography was tested and found to be a useful method for the assessment of hydronephrosis in newborn children. Follow up investigations of 7 children during the first weeks and months post partum revealed valuable diagnostic results in all cases. There was no sign that the diagnostic potential of diuresis renography was in any way restricted by as yet incompletely developed renal function during the first months of life. (Author, shortened by Quittner)

  17. Detection of parathyroid adenomas using a monophasic dual-energy computed tomography acquisition: diagnostic performance and potential radiation dose reduction

    International Nuclear Information System (INIS)

    Leiva-Salinas, Carlos; Flors, Lucia; Durst, Christopher R.; Hou, Qinghua; Mukherjee, Sugoto; Patrie, James T.; Wintermark, Max

    2016-01-01

    The aims of the study were to compare the diagnostic performance of a combination of virtual non-contrast (VNC) images and arterial images obtained from a single-phase dual-energy CT (DECT) acquisition and standard non-contrast and arterial images from a biphasic protocol and to study the potential radiation dose reduction of the former approach. All DECT examinations performed for evaluation of parathyroid adenomas during a 13-month period were retrospectively reviewed. An initial single-energy unenhanced acquisition was followed by a dual-energy arterial phase acquisition. ''Virtual non-contrast images'' were generated from the dual-energy acquisition. Two independent and blinded radiologists evaluated three different sets of images during three reading sessions: single arterial phase, single-phase DECT (virtual non-contrast and arterial phase), and standard biphasic protocol (true non-contrast and arterial phase). The accuracy of interpretation in lateralizing an adenoma to the side of the neck and localizing it to a quadrant in the neck was evaluated. Sixty patients (mean age, 65.5 years; age range, 38-87 years) were included in the study. The lateralization and localization accuracy, sensitivity, and positive predicted value (PPV) and negative predicted value (NPV) of the different image datasets were comparable. The combination of VNC and arterial images was more specific than arterial images alone to lateralize a parathyroid lesion (OR = 1.93, p = 0.043). The use of the single-phase protocol resulted in a calculated radiation exposure reduction of 52.8 %. Virtual non-contrast and arterial images from a single DECT acquisition showed similar diagnostic accuracy than a biphasic protocol, providing a significant dose reduction. (orig.)

  18. Detection of parathyroid adenomas using a monophasic dual-energy computed tomography acquisition: diagnostic performance and potential radiation dose reduction

    Energy Technology Data Exchange (ETDEWEB)

    Leiva-Salinas, Carlos; Flors, Lucia; Durst, Christopher R.; Hou, Qinghua; Mukherjee, Sugoto [University of Virginia, Department of Radiology, Division of Neuroradiology, Charlottesville, VA (United States); Patrie, James T. [University of Virginia, Department of Public Health Sciences, Charlottesville, VA (United States); Wintermark, Max [Stanford University, Department of Radiology, Palo Alto, CA (United States)

    2016-11-15

    The aims of the study were to compare the diagnostic performance of a combination of virtual non-contrast (VNC) images and arterial images obtained from a single-phase dual-energy CT (DECT) acquisition and standard non-contrast and arterial images from a biphasic protocol and to study the potential radiation dose reduction of the former approach. All DECT examinations performed for evaluation of parathyroid adenomas during a 13-month period were retrospectively reviewed. An initial single-energy unenhanced acquisition was followed by a dual-energy arterial phase acquisition. ''Virtual non-contrast images'' were generated from the dual-energy acquisition. Two independent and blinded radiologists evaluated three different sets of images during three reading sessions: single arterial phase, single-phase DECT (virtual non-contrast and arterial phase), and standard biphasic protocol (true non-contrast and arterial phase). The accuracy of interpretation in lateralizing an adenoma to the side of the neck and localizing it to a quadrant in the neck was evaluated. Sixty patients (mean age, 65.5 years; age range, 38-87 years) were included in the study. The lateralization and localization accuracy, sensitivity, and positive predicted value (PPV) and negative predicted value (NPV) of the different image datasets were comparable. The combination of VNC and arterial images was more specific than arterial images alone to lateralize a parathyroid lesion (OR = 1.93, p = 0.043). The use of the single-phase protocol resulted in a calculated radiation exposure reduction of 52.8 %. Virtual non-contrast and arterial images from a single DECT acquisition showed similar diagnostic accuracy than a biphasic protocol, providing a significant dose reduction. (orig.)

  19. Voltage-Gated Potassium Channels Kv1.3--Potentially New Molecular Target in Cancer Diagnostics and Therapy.

    Science.gov (United States)

    Teisseyre, Andrzej; Gąsiorowska, Justyna; Michalak, Krystyna

    2015-01-01

    Voltage-gated potassium channels, Kv1.3, which were discovered in 1984, are integral membrane proteins which are activated ("open") upon change of the cell membrane potential, enabling a passive flux of potassium ions across the cell membrane. The channels are expressed in many different tissues, both normal and cancer. Since 2005 it has been known that the channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane. The activity of Kv1.3 channels plays an important role, among others, in setting the cell resting membrane potential, cell proliferation, apoptosis and volume regulation. For some years, these channels have been considered a potentially new molecular target in both the diagnostics and therapy of some cancer diseases. This review article focuses on: 1) changes of expression of the channels in cancer disorders with special regard to correlations between the channels' expression and stage of the disease, 2) influence of inhibitors of Kv1.3 channels on proliferation and apoptosis of cancer cells, 3) possible future applications of Kv1.3 channels' inhibitors in therapy of some cancer diseases. In the last section, the results of studies performed in our Laboratory of Bioelectricity on the influence of selected biologically active plant-derived compounds from the groups of flavonoids and stilbenes and their natural and synthetic derivatives on the activity of Kv1.3 channels in normal and cancer cells are reviewed. A possible application of some compounds from these groups to support therapy of cancer diseases, such as breast, colon and lymph node cancer, and melanoma or chronic lymphocytic leukemia (B-CLL), is announced.

  20. Transferrin Level Before Treatment and Genetic Polymorphism in HFE Gene as Predictive Markers for Response to Adalimumab in Crohn's Disease Patients.

    Science.gov (United States)

    Repnik, Katja; Koder, Silvo; Skok, Pavel; Ferkolj, Ivan; Potočnik, Uroš

    2016-08-01

    Tumor necrosis factor α inhibitors (anti-TNF) have improved treatment of several complex diseases, including Crohn's disease (CD). However, the effect varies and approximately one-third of the patients do not respond. Since blood parameters as well as genetic factors have shown a great potential to predict response during treatment, the aim of the study was to evaluate response to anti-TNF treatment with adalimumab (ADA) between genes HFE and TF and haematological parameters in Slovenian refractory CD patients. Single nucleotide polymorphisms (SNPs) rs1799852 in gene TF and rs2071303 in gene HFE were genotyped in 68 refractory CD patients for which response has been measured using inflammatory bowel disease questionnaire (IBDQ) index. Haematological parameters and IBDQ index were determined before therapy and after 4, 12, 20 and 30 weeks. We found novel strong association between SNP rs2071303 in gene HFE and response to ADA treatment, particularly patients with G allele comparing to A allele had better response after 20 weeks (p = 0.008). Further, we found strong association between transferrin level at baseline and treatment response after 12, 20 and 30 weeks, where average transferrin level before therapy was lower in responders (2.38 g/L) compared to non-responders (2.89 g/L, p = 0.005). Association was found between transferrin level in week 30 and SNP rs1799852 (p = 0.023), and between MCHC level before treatment and SNP rs2071303 (p = 0.007). Our results suggest that SNP in gene HFE as well as haematological markers serve as promising prognostic markers of response to anti-TNF treatment in CD patients.

  1. Diagnostic potential of virtual bronchoscopy: advantages in comparison with axial CT slices, MPR and mIP?

    International Nuclear Information System (INIS)

    Rapp-Bernhardt, U.; Doehring, W.; Bernhardt, T.M.; Welte, T.; Kropf, S.

    2000-01-01

    The aim of this study was to evaluate the diagnostic potential of virtual endoscopy (VE) and to compare it with axial CT slices, multiplanar reconstructions (MPR), minimal intensity projections (mIP), and bronchoscopy in patients diagnosed with bronchogenic carcinoma. Thirty patients underwent a spiral CT. Axial CT images were transferred to an Onyx workstation (Silicon Graphics, Sun Microsystems, Mountain View, Calif.) for performing virtual endoscopy. Accuracy for this procedure was tested by three radiologists on a monitor in comparison with axial CT slices, MPR, mIP, and bronchoscopy concerning the localization and degree of stenoses. Endoluminal tumors were identified by virtual bronchoscopy with no statistically significant difference of localization or grading of stenosis in comparison with bronchoscopy, axial CT slices, MPR and mIP. Axial CT slices, MPR, and mIP showed poorer results with over- or underestimation of stenoses compared with VE and bronchoscopy. Passing of stenoses was only possible with VE in 5 patients. Virtual endoscopy is a non-invasive method for identification of endoluminal tumors and is comparable to real bronchoscopy. (orig.)

  2. Diagnostic potential of virtual bronchoscopy: advantages in comparison with axial CT slices, MPR and mIP?

    Energy Technology Data Exchange (ETDEWEB)

    Rapp-Bernhardt, U.; Doehring, W.; Bernhardt, T.M. [Department of Diagnostic Radiology, Otto-von-Guericke University, Magdeburg (Germany); Welte, T. [Department of Cardiology, Angiology, and Pneumology, Otto-von-Guericke University, Magdeburg (Germany); Kropf, S. [Department of Biometrics and Medical Informatics, Otto-von-Guericke University, Magdeburg (Germany)

    2000-06-01

    The aim of this study was to evaluate the diagnostic potential of virtual endoscopy (VE) and to compare it with axial CT slices, multiplanar reconstructions (MPR), minimal intensity projections (mIP), and bronchoscopy in patients diagnosed with bronchogenic carcinoma. Thirty patients underwent a spiral CT. Axial CT images were transferred to an Onyx workstation (Silicon Graphics, Sun Microsystems, Mountain View, Calif.) for performing virtual endoscopy. Accuracy for this procedure was tested by three radiologists on a monitor in comparison with axial CT slices, MPR, mIP, and bronchoscopy concerning the localization and degree of stenoses. Endoluminal tumors were identified by virtual bronchoscopy with no statistically significant difference of localization or grading of stenosis in comparison with bronchoscopy, axial CT slices, MPR and mIP. Axial CT slices, MPR, and mIP showed poorer results with over- or underestimation of stenoses compared with VE and bronchoscopy. Passing of stenoses was only possible with VE in 5 patients. Virtual endoscopy is a non-invasive method for identification of endoluminal tumors and is comparable to real bronchoscopy. (orig.)

  3. Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease.

    Science.gov (United States)

    Bukhari, Syed Nasir Abbas; Jantan, Ibrahim

    2015-01-01

    There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.

  4. Ocular vestibular evoked myogenic potentials to vertex low frequency vibration as a diagnostic test for superior canal dehiscence.

    Science.gov (United States)

    Verrecchia, Luca; Westin, Magnus; Duan, Maoli; Brantberg, Krister

    2016-04-01

    To explore ocular vestibular evoked myogenic potentials (oVEMP) to low-frequency vertex vibration (125 Hz) as a diagnostic test for superior canal dehiscence (SCD) syndrome. The oVEMP using 125 Hz single cycle bone-conducted vertex vibration were tested in 15 patients with unilateral superior canal dehiscence (SCD) syndrome, 15 healthy controls and in 20 patients with unilateral vestibular loss due to vestibular neuritis. Amplitude, amplitude asymmetry ratio, latency and interaural latency difference were parameters of interest. The oVEMP amplitude was significantly larger in SCD patients when affected sides (53 μVolts) were compared to non-affected (17.2 μVolts) or compared to healthy controls (13.6 μVolts). Amplitude larger than 33.8 μVolts separates effectively the SCD ears from the healthy ones with sensitivity of 87% and specificity of 93%. The other three parameters showed an overlap between affected SCD ears and non-affected as well as between SCD ears and those in the two control groups. oVEMP amplitude distinguishes SCD ears from healthy ones using low-frequency vibration stimuli at vertex. Amplitude analysis of oVEMP evoked by low-frequency vertex bone vibration stimulation is an additional indicator of SCD syndrome and might serve for diagnosing SCD patients with coexistent conductive middle ear problems. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin-Receptor Internalization Pathway.

    Science.gov (United States)

    Schaffert, David H; Okholm, Anders H; Sørensen, Rasmus S; Nielsen, Jesper S; Tørring, Thomas; Rosen, Christian B; Kodal, Anne Louise B; Mortensen, Michael R; Gothelf, Kurt V; Kjems, Jørgen

    2016-05-01

    DNA origami provides rapid access to easily functionalized, nanometer-sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major obstacle in the development of DNA-based delivery platforms. Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA-directed, site-selective labeling technique to retain ligand functionality. A combination of confocal fluorescence microscopy and quantitative (qPCR) techniques shows up to 22-fold increased cytoplasmic uptake compared to unmodified structures and with an efficiency that correlates to the number of transferrin molecules on the origami surface. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Serum iron, ferritin, transferrin and haptoglobin concentration variations during repeated show jumping competition in horse

    Directory of Open Access Journals (Sweden)

    Anna Assenza

    2016-01-01

    Full Text Available Modifications of the iron profile in athlete horses during two international three star (*** show jumping competitions performed in two consecutive weekends were evaluated. Serum iron, ferritin, transferrin, and haptoglobin were assessed in 12 well-trained Italian Saddle horses. Blood samplings were performed before the first day of competition (R1, within 10 min from the end of each competition (J1, J2 and on the day after competition (R2. The same plan was followed during the second weekend (J3, J4 and R3. One-way repeated measures analysis of variance (ANOVA was applied on obtained data, and a significant effect of exercise (P < 0.05 on all studied indices was found. These results suggest that serum iron, transferrin, ferritin and haptoglobin are responsive to intense exercise and could be considered important indicators that may give important information about the horse’s performance.

  7. (111)Indium-transferrin for localization and quantification of gastrointestinal protein loss

    DEFF Research Database (Denmark)

    Simonsen, Jane Angel; Braad, Poul-Erik; Veje, Annegrete

    2009-01-01

    Objective. To evaluate the indium-111 ((111)In)-transferrin method as a means of localization and quantification of gastrointestinal protein loss. Methods. Fourteen patients and 15 healthy subjects underwent an (111)In-transferrin study consisting of abdominal scintigraphy, whole-body counting...... measurement and determination of plasma activity of (111)In during the course of 5 days. Two of the patients went through a subsequent chromium-51-trichloride test with analysis of radioactivity in faeces in order to compare the results of the two methods. Results. The patients had a mean+/-SEM whole-body...... loss of (111)In of 10.9+/-2.9% for 96 h, while the healthy controls lost 1.8+/-1.3% (p=0.0045). The decay in plasma activity followed biexponential kinetics. The characteristic plasma transit time was 5.0+/-1.0 h in patients and 12.1+/-1.5 h in controls (p=0.0007). Scintigraphically, patients had...

  8. Effect of wortmannin and phorbol ester on Paramecium fluid-phase uptake in the presence of transferrin

    Directory of Open Access Journals (Sweden)

    J Wiejak

    2009-12-01

    Full Text Available The kinetics of the uptake of the fluid phase marker Lucifer Yellow (LY, and its alteration by wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI-3K, and the PKC modulators: GF 109203 X, an inhibitor, and phorbol ester, an activator was studied in eukaryotic model Paramecium aurelia. Spectrophotometric quantification of LY accumulation was performed in the presence or absence of transferrin, a marker of receptor-mediated endocytosis. Internalization of LY showed a curvilinear kinetics: the high initial rate of LYuptake (575 ng LY/ mg protein /hr decreased almost 5-fold within 15 min, reaching plateau at 126 ng/ mg protein /hr. Transferrin induced a small increase (7.5% in the fluid phase uptake rate (after 5 min followed by a small decrease at longer incubation times. Lucifer Yellow and transferrin (visualized by streptavidin– FITC were localized in Paramecium by 3-D reconstruction by confocal microscopy. LY showed a scattered, diffuse fluorescence typical of fluid phase uptake whereas transferrin accumulated in membrane-surrounded endosomes. Wortmannin did not affect LY accumulation but decreased it when transferrin was present in the incubation medium. This suggests an effect on the transferrin uptake pathway, presumably on the stage of internalization in “mixing” endosomes to which transferrin and LY were targeted. Phorbol ester diminished LY accumulation by 22% and this effect persisted up to 25 min of incubation. PKC inhibitor did not affect LY uptake. However, in the presence of transferrin, the LY uptake increased within the first 15 minutes followed by a rapid 20% decrease in comparison to the control. Such an effect of PKC modulators suggests that PMA action on fluid phase uptake is not directly mediated by PKC.

  9. Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition.

    Science.gov (United States)

    Sheokand, Navdeep; Kumar, Santosh; Malhotra, Himanshu; Tillu, Vikas; Raje, Chaaya Iyengar; Raje, Manoj

    2013-06-01

    The long held view is that mammalian cells obtain transferrin (Tf) bound iron utilizing specialized membrane anchored receptors. Here we report that, during increased iron demand, cells secrete the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which enhances cellular uptake of Tf and iron. These observations could be mimicked by utilizing purified GAPDH injected into mice as well as when supplemented in culture medium of model cell lines and primary cell types that play a key role in iron metabolism. Transferrin and iron delivery was evaluated by biochemical, biophysical and imaging based assays. This mode of iron uptake is a saturable, energy dependent pathway, utilizing raft as well as non-raft domains of the cell membrane and also involves the membrane protein CD87 (uPAR). Tf internalized by this mode is also catabolized. Our research demonstrates that, even in cell types that express the known surface receptor based mechanism for transferrin uptake, more transferrin is delivered by this route which represents a hidden dimension of iron homeostasis. Iron is an essential trace metal for practically all living organisms however its acquisition presents major challenges. The current paradigm is that living organisms have developed well orchestrated and evolved mechanisms involving iron carrier molecules and their specific receptors to regulate its absorption, transport, storage and mobilization. Our research uncovers a hidden and primitive pathway of bulk iron trafficking involving a secreted receptor that is a multifunctional glycolytic enzyme that has implications in pathological conditions such as infectious diseases and cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Clone and expression of human transferrin receptor gene: a marker gene for magnetic resonance imaging

    International Nuclear Information System (INIS)

    Li Li; Liu Lizhi; Lv Yanchun; Liu Xuewen; Cui Chunyan; Wu Peihong; Liu Qicai; Ou Shanxing

    2007-01-01

    Objective: To clone human transferrin receptor (hTfR) gene and construct expression vector producing recombination protein. Methods: Human transferrin receptor gene cDNA was amplified by RT-PCR from human embryonic liver and lung tissue. Recombinant pcDNA3-hTfR and pEGFP-Cl-hTfR plasmids were constructed and confirmed by DNA sequencing. These plasmids were stably transfected into the HEK293 cells. The protein expression in vitro was confirmed by Western Blot. The efficiency of expression and the location of hTfR were also investigated by fluorescence microscopy and confocal fluorescence microscopy. Results: The full length cDNA of hTfR gene (2332 bp) was cloned and sequenced. The hTfR (190 000) was overexpressed in transfected HEK293 cells by Western blot analysis. Fluorescence micrographs displayed that the hTfR was expressed at high level and located predominantly in the cell surface. Conclusions: Human transferrin receptor (hTfR) gene has been successfully cloned and obtained high-level expression in HEK293 cells, and the recombination protein of hTfR distributed predominantly in the cell membrane. (authors)

  11. Soluble transferrin receptor: a differentiating marker between iron deficiency anaemia and anaemia of chronic disorders

    International Nuclear Information System (INIS)

    Saboor, M.; Moinuddin, A.; Naureen, A.

    2012-01-01

    Background: Iron deficiency anaemia and anaemia of chronic disorders are the two major causes of microcytic and hypochromic anaemia. Many times the diagnosis of these conditions becomes difficult through conventional laboratory tests. Determination of soluble transferrin receptors is a helpful laboratory test for the differential diagnosis of these conditions. The study was conducted to evaluate the role of soluble transferrin receptors in the differential diagnosis between iron deficiency anaemia and anaemia of chronic disorders. Methods: A total of 80 blood samples were evaluated, i.e., 20 samples from normal adult male, 20 samples from normal adult female, 20 samples from iron deficiency anaemia group and 20 samples from patients with anaemia of chronic disorders. Soluble transferrin receptors were determined by ELISA technique using Quantikine IVD kit (R and D Systems). Results: There was significant difference in the levels of sTfR in iron deficiency anaemia and anaemia of chronic disorders. Statistically non-significant difference was observed between the levels of sTfR in patients with anaemia of chronic disorders as compared to normal control group. Conclusion: The sTfR determination can be used as a reliable differentiating marker in the diagnosis of iron deficiency anaemia and anaemia of chronic disorders. (author)

  12. Detection of cerebrospinal fluid leakage by specific measurement of transferrin glycoforms.

    Science.gov (United States)

    Kwon, Seok-Joon; Zhang, Fuming; Dordick, Jonathan S; Sonstein, William J; Linhardt, Robert J

    2015-10-01

    A simple and rapid detection of cerebrospinal fluid (CSF) leakage would benefit spine surgeons making critical postoperative decisions on patient care. We have assessed novel approaches to selectively determine CSF β2-transferrin (β2TF), an asialo-transferrin (aTF) biomarker, without interference from serum sialo-transferrin (sTF) in test samples. First, we performed mild periodate oxidation to selectively generate aldehyde groups in sTF for capture with magnetic hydrazide microparticles, and selective removal with a magnetic separator. Using this protocol sTF was selectively removed from mixtures of CSF and serum containing CSF aTF (β2TF) and serum sTF, respectively. Second, a two-step enzymatic method was developed with neuraminidase and galactose oxidase for generating aldehyde groups in sTF present in CSF and serum mixtures for magnetic hydrazide microparticle capture. After selectively removing sTF from mixtures of CSF and serum, ELISA could detect significant TF signal only in CSF, while the TF signal in serum was negligible. The new approach for selective removal of only sTF in test samples will be promising for the required intervention by a spine surgeon. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin

    International Nuclear Information System (INIS)

    Mintun, M.A.; Dennis, D.R.; Welch, M.J.; Mathias, C.J.; Schuster, D.P.

    1987-01-01

    We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-( 68 Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of [ 68 Ga]citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escape rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury

  14. Plasmid pORF-hTRAIL targeting to glioma using transferrin-modified polyamidoamine dendrimer

    Directory of Open Access Journals (Sweden)

    Gao S

    2015-12-01

    Full Text Available Song Gao,1,* Jianfeng Li,2 Chen Jiang,2 Bo Hong,3 Bing Hao4,* 1Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 3Department of Pathology, The Second Affiliated Hospital, 4Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A gene drug delivery system for glioma therapy based on transferrin (Tf-modified polyamidoamine dendrimer (PAMAM was prepared. Gene drug, tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL-encoding plasmid open reading frame (pORF-hTRAIL, Trail, was condensed by Tf-modified PAMAM to form nanoparticles (NPs. PAMAM-PEG-Tf/DNA NPs showed higher cellular uptake, in vitro gene expression, and cytotoxicity than PAMAM-PEG/DNA NPs in C6 cells. The in vivo targeting efficacy of NPs was visualized by ex vivo fluorescence imaging. Tf-modified NPs showed obvious glioma-targeting trend. Plasmid encoding green fluorescence protein (GFP was also condensed by modified or unmodified PAMAM to evaluate the in vivo gene expression level. The PAMAM-PEG-Tf/plasmid encoding enhanced green fluorescence protein (pEGFP NPs exhibited higher GFP expression level than PAMAM-PEG/pEGFP NPs. TUNEL assay revealed that Tf-modified NPs could induce much more tumor apoptosis. The median survival time of PAMAM-PEG-Tf/Trail-treated rats (28.5 days was longer than that of rats treated with PAMAM-PEG/Trail (25.5 days, temozolomide (24.5 days, PAMAM-PEG-Tf/pEGFP (19 days, or saline (17 days. The therapeutic effect was further confirmed by magnetic resonance imaging. This study demonstrated that targeting gene delivery system had potential application for the

  15. Online Diagnostic Assessment: Potential and Limitations (The case of DIALANG in the Greek Junior High School Context

    Directory of Open Access Journals (Sweden)

    Vassiliki Baglantzi

    2012-02-01

    Full Text Available This study explored the potential of DIALANG to serve placement purposes in the 1st grade of Greek state junior high school. The DIALANG system of language assessment is an application of the Common European Framework of Reference (Council of Europe, 2001, which assesses the user’s level in five skills (listening, writing, reading, vocabulary and structures and places them on one of the six (A1-C2 CEFR levels. It is a valid and reliable, online diagnostic test, which makes extensive use of self-assessment and provides several types of feedback. So far, DIALANG has been mainly used by adult learners in 14 languages in self-access, low-stakes contexts around Europe. However, the research focus in this study is whether DIALANG can replace teacher made placement tests for younger learners of English. Teacher-made tests are often criticized on the grounds of validity, reliability and content, therefore the use of a standardized alternative would facilitate placement procedures in a valid and reliable way. 20 students took DIALANG and then reported on their experience through a questionnaire. The students were also involved in self-assessing their reading, writing and listening skills using the DIALANG self-assessment statements. Their teacher also used the DIALANG scales to assess the students’ proficiency level in these three skills. The research findings showed that DIALANG can be a highly practical and useful placement tool provided that it is limited to the assessment of three skills (listening, writing and reading out of the five it can assess. Results also showed that neither the students nor the teacher are adequately familiar with the DIALANG statements and consequently the CEFR skills level descriptors, although these levels are extensively used in the description of textbooks, language courses and exams in the ELT field in Greece.

  16. Plasma lysosphingomyelin demonstrates great potential as a diagnostic biomarker for Niemann-Pick disease type C in a retrospective study.

    Directory of Open Access Journals (Sweden)

    Richard W D Welford

    Full Text Available Niemann-Pick disease type C (NP-C is a devastating, neurovisceral lysosomal storage disorder which is characterised by variable manifestation of visceral signs, progressive neuropsychiatric deterioration and premature death, caused by mutations in the NPC1 and NPC2 genes. Due to the complexity of diagnosis and the availability of an approved therapy in the EU, improved detection of NP-C may have a huge impact on future disease management. At the cellular level dysfunction or deficiency of either the NPC1 or NPC2 protein leads to a complex intracellular endosomal/lysosomal trafficking defect, and organ specific patterns of sphingolipid accumulation. Lysosphingolipids have been shown to be excellent biomarkers of sphingolipidosis in several enzyme deficient lysosomal storage disorders. Additionally, in a recent study the lysosphingolipids, lysosphingomyelin (SPC and glucosylsphingosine (GlcSph, appeared to be elevated in the plasma of three adult NP-C patients. In order to investigate the clinical utility of SPC and GlcSph as diagnostic markers, an in-depth fit for purpose biomarker assay validation for measurement of these biomarkers in plasma by liquid chromatography-tandem mass spectrometry was performed. Plasma SPC and GlcSph are stable and can be measured accurately, precisely and reproducibly. In a retrospective analysis of 57 NP-C patients and 70 control subjects, median plasma SPC and GlcSph were significantly elevated in NP-C by 2.8-fold and 1.4-fold respectively. For miglustat-naïve NP-C patients, aged 2-50 years, the area under the ROC curve was 0.999 for SPC and 0.776 for GlcSph. Plasma GlcSph did not correlate with SPC levels in NP-C patients. The data indicate excellent potential for the use of lysosphingomyelin in NP-C diagnosis, where it could be used to identify NP-C patients for confirmatory genetic testing.

  17. Potential diagnostic value of 131I-MIBG myocardial scintigraphy in discrimination between Alzheimer disease and dementia with Lewy bodies.

    Science.gov (United States)

    Abbasi, Mehrshad; Ghalandari, Nafise; Farzanefar, Saeed; Aghamollaii, Vajiheh; Ahmadi, Mona; Ganji, Morsaleh; Afarideh, Mohsen; Loloee, Sogol; Naseri, Maryam; Tafakhori, Abbas

    2017-12-01

    Clinical difficulty to discriminate between the Alzheimer disease (AD) and dementia with Lewy bodies (DLB) has led researchers to focus on highly sensitive functional imaging modalities. The aim of the present study was to assess 131 I-MIBG cardiac imaging to distinguish between AD and DLB. Seventeen patients who were known cases of dementia underwent 131 I-MIBG myocardial scintigraphy to differentiate AD from DLB. Planar and 131 I-MIBG SPECT were obtained 2h after the injection of 1mCi 131 I-MIBG on a dual head gamma camera. The visual assessment of the heart uptake compared with lungs and the quantification based on the heart to mediastinal ratio (HMR) were done. The cardiac receiver operating characteristic (ROC) curve was designed for the optimal HMR cut-off values to predict the diagnoses of the patients. The diagnoses were clinically confirmed during the follow up of 14±8.2 months. Out of 17 patients (13 males; 76.5%), 10 patients had AD (7 males; 70%) and 7 patients had DLB (6 males; 85%). The pooled HMR was 1.74±0.33 in the study population; with 1.95±0.22 in the AD group and 1.43±0.20 in the DLB group to demonstrate significantly different HMR scores between patients with AD and DLB (p value=0.001). The visual interpretation was positive in 10 patients (accuracy of 88.2%). The shortest distance on the ROC curve to the optimal value corresponding to HMR=1.57 identified 10 patients with a high HMR (positive cardiac uptake) and 7 patients with a low HMR (negative cardiac uptake), the accuracy calculated at 88.2%. 131 I-MIBG myocardial scintigraphy is a potential alternative diagnostic modality for discrimination between AD and DLB when 123 I is not available. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Rapid screening of transferrin-binders in the flowers of Bauhinia blakeana Dunn by on-line high-performance liquid chromatography-diode-array detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry-transferrin-fluorescence detection system.

    Science.gov (United States)

    Liu, Meixian; Dong, Jing; Lin, Zongtao; Niu, Yanyan; Zhang, Xiaotian; Jiang, Haixiu; Guo, Ning; Li, Wei; Wang, Hong; Chen, Shizhong

    2016-06-10

    Transferrin (Transferrin, TRF, TF) has drawn increasing attention in cancer therapy due to its potential applications in drug delivery. TF receptor, highly expressed in tumor cells, recognizes and transports Fe(3+)-TF into cells to release iron into cytoplasm. Thus, discovering TF-binding compounds has become an active research area and is of great importance for target therapy. In this study, an on-line analysis method was established for screening TF-binding compounds from the flowers of Bauhinia blakeana Dunn using a high-performance liquid chromatography-diode-array detector-multi-stage mass spectrometry-transferrin-fluorescence detector (HPLC-DAD-MS(n)-TF-FLD) method. As a result, 33 of 80 identified or tentatively characterized compounds in the sample were TF-binding active. Twenty-five flavonol glycosides and eight phenolic acids were identified as TF-binders. Twelve of these active compounds together with six standard compounds were used to study the dose-response effects and structure-activity relationships of flavonoids and phenolic acids. The method was validated by vitexin with a good linearity in the range of concentrations used in the study. The limit of detection for vitexin was 0.1596 nmol. Our study indicated that the established method is simple, rapid and sensitive for screening TF-binding active compounds in the extract of Bauhinia blakeana Dunn, and therefore is important for discovering potential anti-cancer ingredients from complex samples for TF related drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Transferrin adsorption onto PLGA nanoparticles governs their interaction with biological systems from blood circulation to brain cancer cells.

    Science.gov (United States)

    Chang, Jiang; Paillard, Archibald; Passirani, Catherine; Morille, Marie; Benoit, Jean-Pierre; Betbeder, Didier; Garcion, Emmanuel

    2012-06-01

    Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumors. Behaviour of PLGA-nanoparticles (NPs) was here investigated as a function of their protein adsorption characteristics at the different biological interfaces they are expected to face in order to reach brain cancer cells. NPs were studied for size, zeta potential, blood half-life, in vitro endocytic behavior and in vivo accumulation within healthy rat brain and brain tumors. While slightly modifying size (80 to 90 nm) and zeta potential (-44 to -32 mV) protein coating of PLGA-NPs by bovine serum albumin (BSA) or transferrin (Tf) greatly prolonged their blood half-life when intravenously injected in rats and mice. In contrast with THP-1 monocytes, differentiated THP-1 macrophages, F98 glioma cells and astrocytes internalized BSA- and Tf-NPs in vitro. Increase of Tf-NP uptake by F98 cells through caveolae- and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, in vivo targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors. Taken together, those data evidence that Tf-NPs represent an interesting nanomedicine to deliver anticancer drugs to glioma cells through systemic or locoregional strategies at early and late tumor stages.

  20. THE PHYSICAL ORIGIN AND THE DIAGNOSTIC POTENTIAL OF THE SCATTERING POLARIZATION IN THE Li I RESONANCE DOUBLET AT 6708 A

    International Nuclear Information System (INIS)

    Belluzzi, Luca; Landi Degl'Innocenti, Egidio; Trujillo Bueno, Javier

    2009-01-01

    High-sensitivity measurements of the linearly polarized solar limb spectrum produced by scattering processes in quiet regions of the solar atmosphere showed that the Q/I profile of the lithium doublet at 6708 A has an amplitude ∼10 -4 and a curious three-peak structure, qualitatively similar to that found and confirmed by many observers in the Na I D 2 line. Given that a precise measurement of the scattering polarization profile of the lithium doublet lies at the limit of the present observational possibilities, it is worthwhile to clarify the physical origin of the observed polarization, its diagnostic potential, and what kind of Q/I shapes can be expected from theory. To this end, we have applied the quantum theory of atomic level polarization taking into account the hyperfine structure of the two stable isotopes of lithium, as well as the Hanle effect of a microturbulent magnetic field of arbitrary strength. We find that quantum interferences between the sublevels pertaining to the upper levels of the D 2 and D 1 line transitions of lithium do not cause any observable effect on the emergent Q/I profile. Our theoretical calculations show that only two Q/I peaks can be expected, with the strongest one caused by the D 2 line of 7 Li I and the weakest one due to the D 2 line of 6 Li I. Interestingly, we find that these two peaks in the theoretical Q/I profile stand out clearly only when the kinetic temperature of the thin atmospheric region that produces the emergent spectral line radiation is lower than 4000 K. The fact that such a thin atmospheric region is located around a height of 200 km in standard semi-empirical models, where the kinetic temperature is about 5000 K, leads us to suggest that the most likely Q/I profile produced by the Sun in the lithium doublet should be slightly asymmetric and dominated by the 7 Li I peak.

  1. Managing uncertainty: a qualitative study of GPs' views on the diagnosis and immediate management of transient ischaemic attack and the potential of a diagnostic tool.

    Science.gov (United States)

    Bose, Priyanka; Tarrant, Carolyn; Mistri, Amit K; Wilson, Andrew

    2018-04-12

    Most patients with transient ischaemic attack (TIA) present to their GP. Early identification and treatment reduces the risk of subsequent stroke and consequent disability and mortality. To explore GPs' views on the diagnosis and immediate management of suspected TIA, and the potential utility of a diagnostic tool. This is a qualitative interview study based in Leicestershire, UK. A purposive sample of 10 GPs participated in 30-minute semi-structured telephone interviews. Data were analysed thematically. GPs reported that TIA was more likely to be suspected when patients were more obvious candidates for TIA based on their history, characteristics and symptom presentation. Referrals were in part a strategy to manage risk under conditions of uncertainty and to seek reassurance. GPs valued using a TIA risk stratification tool but felt this did not inform their diagnostic decision making. A diagnostic tool for TIA in primary care was seen to have potential to improve the decision-making process about diagnosis and management and enhance confidence of GPs, particularly in ruling out TIAs. GPs saw benefits of using hard thresholds, but remained concerned about missing TIAs and saw a tool as an adjunct to clinical judgement. GPs weigh up the likelihood of TIA in the context of assessments of candidacy and diverse, often vague, symptoms. A diagnostic tool could support GPs in this process and help reduce reliance on referrals to TIA clinics for reassurance, provided the tool was designed to support decision making in cases of less 'typical' presentations.

  2. The potential impact of various diagnostic strategies in cases of chronic pain syndromes associated with lumbar spine degeneration

    Directory of Open Access Journals (Sweden)

    Bokov A

    2013-04-01

    Full Text Available Andrey Bokov, Olga Perlmutter, Alexander Aleynik, Marina Rasteryaeva, Sergey Mlyavykh Scientific Research Institute of Traumatology and Orthopedics, Nizhniy Novgorod, Russian Federation Purpose: To study the possible effects of various diagnostic strategies and the relative contribution of various structures in order to determine the optimal diagnostic strategy in treating patients with noncompressive pain syndromes. Study design: Prospective, nonrandomized cohort study of 83 consecutive patients with noncompressive pain syndromes resistant to repeated courses of conservative treatment. The follow-up period was 18 months. Results: Nucleoplasty was effective in cases of discogenic pain; the consequences related to false positive results of the discography were significant. The most specific criterion was 80% pain relief after facet joint blocks, whereas 50% pain relief and any subjective pain relief were not associated with a significant increase in the success rate. A considerable rate of false negative results was associated with 80% pain relief, whereas 50% pain relief after facet joint blocks showed the optimal ratio of sensitivity and specificity. Facet joint pain was detected in 50.6% of cases (95% confidence interval 44.1%–66.3%, discogenic pain in 16.9% cases (95% confidence interval 9.5%–26.7%, and sacroiliac joint pain in 7.2% cases (95% confidence interval 2.7%–15%. It was impossible to differentiate the main source of pain in 25.3% of cases. Conclusion: It is rational to adjust the diagnostic algorithm to the probability of detecting a particular pain source and, in doing so, reduce the number of invasive diagnostic measures to evaluate a pain source. False positive results of diagnostic measures can negatively affect the overall efficacy of a particular technology; therefore, all reasons for the failure should be studied in order to reach an unbiased conclusion. In choosing diagnostic criteria, not only should the success rate

  3. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Aviral, E-mail: draviraljain@gmail.com; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi [Adina Institute of Pharmaceutical Sciences, Pharmaceutics Research Laboratory, Department of Pharmaceutics (India)

    2013-03-15

    Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 {+-} 3.22 nm with entrapment efficiency of 69.83 {+-} 2.52 and 249 {+-} 2.61 nm with entrapment efficiency decreased to 64.21 {+-} 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

  4. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

    Science.gov (United States)

    Jain, Aviral; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi

    2013-03-01

    Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 ± 3.22 nm with entrapment efficiency of 69.83 ± 2.52 and 249 ± 2.61 nm with entrapment efficiency decreased to 64.21 ± 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

  5. Investigation of the potential of optical coherence tomography (OCT) as a non-invasive diagnostic tool in reproductive medicine

    Science.gov (United States)

    Trottmann, Matthias; Homann, Christian; Leeb, R.; Doering, D.; Kuznetsova, J.; Reese, S.; Stief, C. G.; Koelle, S.; Sroka, R.

    2015-02-01

    Introduction and objective: In Europe, nearly every sixth couple in the reproductive age is involuntarily childless. In about 30%, both male and female reveal fertility problems. In about 10% of infertile men, azoospermia is the underlying cause. As conventional therapeutic options are limited, surgical testicular sperm extraction (TESE) is necessary to obtain sperms for assisted reproductive techniques. Regarding the females, up to 30% of all idiopathic infertilities are due to alterations of the uterine tube So far, no imaging technique, which does not require any labelling, is available to evaluate the male and female genital tract at a microscopic level under in vivo conditions. Thus, the aim of this study was to investigate the potential of optical coherence tomography (OCT) as a non-invasive diagnostic tool in gynaecology and andrology. Material and Methods: Tissues samples from the bovine testis, epididymis, vas deferens, ovary, oviduct (ampulla and isthmus) and uterus were obtained immediately after slaughter (14 cows aged 3 to 8 years and 14 bulls aged 3 to 6 years; breeds: Holstein- Friesian, and Deutsches Fleckvieh). Imaging was done by using the US Food and Drug Administration (FDA) approved probe-based Niris Imaging System (Imalux, Cleveland, Ohio, USA) and the Telesto 1325 nm OCT System and Ganymede 930 nm OCT System (Thorlabs Inc., Dachau, Germany). All images obtained were compared to histological images after paraffin embedding and HE staining. Results: OCT imaging visualized the microarchitecture of the testis, epididymis, spermatic duct and the ovary, oviduct and uterus. Using the Thorlabs systems a axial resolution of approx. 5μm and lateral resolution of 8- 15μm could be achieved. Different optical tissue volumes could be visualized, which depends on the optical penetration depth of the wavelength of the system used. While the tissue volume observed by probe based Imalux-OCT is similar to the used Thorlabs systems, the optical resolution is

  6. A Rare Multifocal Pattern of Type 2 Autoimmune Pancreatitis with Negative IgG4: A Potential Diagnostic Pitfall That May Mimic Multifocal Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Partha Hota

    2018-02-01

    Full Text Available Autoimmune pancreatitis (AIP is an increasingly recognized form of acute pancreatitis characterized by obstructive jaundice with a rapid and dramatic treatment response to steroid therapy. Recently, AIP has been divided into two distinct phenotypes: lymphoplasmocytic sclerosing pancreatitis AIP (type 1 and idiopathic duct-centric pancreatitis AIP (type 2; each of which have their own distinct demographics, diagnostic criteria, and histopathological features. We report, to the best of our knowledge, the first case of a multifocal pattern of type 2 AIP characterized with both CT and MR imaging. This rare imaging pattern of AIP may mimic the appearance of more worrisome malignant etiologies such as multifocal pancreatic adenocarcinoma or lymphoma, with overlapping imaging characteristics potentially complicating or delaying diagnosis. Therefore, recognition of this atypical pattern of AIP and avoidance of this potential diagnostic pitfall is crucial.

  7. Control of heme synthesis during Friend cell differentiation: role of iron and transferrin

    International Nuclear Information System (INIS)

    Laskey, J.D.; Ponka, P.; Schulman, H.M.

    1986-01-01

    In many types of cells the synthesis of σ-aminolevulinic acid (ALA) limits the rate of heme formation. However, results from this laboratory with reticulocytes suggest that the rate of iron uptake from 125 I-transferrin (Tf), rather than ALA synthase activity, limits the rate of heme synthesis in erythroid cells. To determine whether changes occur in iron metabolism and the control of heme synthesis during erythroid cell development Friend erythroleukemia cells induced to erythroid differentiation by dimethylsulfoxide (DMSO) were studied. While added ALA stimulated heme synthesis in uninduced Friend cells (suggesting ALA synthase is limiting) it did not do so in induced cells. Therefore the possibility was investigated that, in induced cells, iron uptake from Tf limits and controls heme synthesis. Several aspects of iron metabolism were investigated using the synthetic iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH). Both induced and uninduced Friend cells take up and utilize Fe for heme synthesis directly from Fe-SIH without the involvement of transferrin and transferrin receptors and to a much greater extent than from saturating levels or 59 Fe-Tf (20 μM). Furthermore, in induced Friend cells 100 μM Fe-SIH stimulated 2- 14 C-glycine incorporation into heme up to 3.6-fold as compared to the incorporation observed with saturating concentrations of Fe-Tf. These results indicate that some step(s) in the pathway of iron from extracellular Tf to protoporphyrin, rather than the activity of ALA synthase, limits and controls the overall rate of heme and possibly hemoglobin synthesis in differentiating Friend erythroleukemia cells

  8. Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin-Receptor Internalization Pathway

    DEFF Research Database (Denmark)

    Schaffert, David Henning; Okholm, Anders Hauge; Sørensen, Rasmus Schøler

    2016-01-01

    DNA origami provides rapid access to easily functionalized, nanometer-sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major obstacle in the development of DNA-based delivery platforms....... Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA-directed, site...... on the origami surface....

  9. Potential of high speed x-ray cinematography as a fuel motion diagnostic for safety test facilities

    International Nuclear Information System (INIS)

    Stalker, K.T.; Choate, L.M.; Posey, L.D.

    1979-01-01

    Experiments have been performed which indicate the feasibility of using X-ray cinematography as a diagnostic tool for monitoring fuel motion in large pin bundle advanced reactor safety tests. This capability was demonstrated by imaging motion in a 37-pin bundle of simulated fuel elements at a data rate of 400 pictures per second using an active detector system coupled with a 10 MeV accelerator. 5 refs

  10. A Potential Tension in DSM-5: The General Definition of Mental Disorder versus Some Specific Diagnostic Criteria.

    Science.gov (United States)

    Amoretti, M Cristina; Lalumera, Elisabetta

    2018-05-30

    The general concept of mental disorder specified in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders is definitional in character: a mental disorder might be identified with a harmful dysfunction. The manual also contains the explicit claim that each individual mental disorder should meet the requirements posed by the definition. The aim of this article is two-fold. First, we shall analyze the definition of the superordinate concept of mental disorder to better understand what necessary (and sufficient) criteria actually characterize such a concept. Second, we shall consider the concepts of some individual mental disorders and show that they are in tension with the definition of the superordinate concept, taking pyromania and narcissistic personality disorder as case studies. Our main point is that an unexplained and not-operationalized dysfunction requirement that is included in the general definition, while being systematically violated by the diagnostic criteria of specific mental disorders, is a logical error. Then, either we unpack and operationalize the dysfunction requirement, and include explicit diagnostic criteria that can actually meet it, or we simply drop it.

  11. GLUT4 in cultured skeletal myotubes is segregated from the transferrin receptor and stored in vesicles associated with TGN

    DEFF Research Database (Denmark)

    Ralston, E; Ploug, Thorkil

    1996-01-01

    of the constitutive endosomal-lysosomal pathway. To address this question, we have investigated the localization of the endogenous GLUT4 in non-stimulated skeletal myotubes from the cell line C2, by immunofluorescence and immunoelectron microscopy. We have used a panel of antibodies to markers of the Golgi complex...... and in vesicles just beyond, i.e. in the structures that constitute the trans-Golgi network (TGN). In myotubes treated with brefeldin A, the immunofluorescence pattern of GLUT4 is modified, but it differs from both Golgi complex markers and TGN38. Instead, it resembles the pattern of the transferrin receptor...... to the GLUT4-containing tubulo-vesicular elements. In brefeldin A-treated cells, a network of tubules of approximately 70 nm diameter, studded with varicosities, stains for both GLUT4 and transferrin receptor, suggesting that brefeldin A has caused fusion of the transferrin receptor and GLUT4-containing...

  12. Hypertension increases urinary excretion of immunoglobulin G, ceruloplasmin and transferrin in normoalbuminuric patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Ohara, Nobumasa; Hanyu, Osamu; Hirayama, Satoshi; Nakagawa, Osamu; Aizawa, Yoshifusa; Ito, Seiki; Sone, Hirohito

    2014-02-01

    Increased urinary excretion of certain plasma proteins, such as immunoglobulin G (IgG), ceruloplasmin and transferrin, with different molecular radii of 55 Å or less and different isoelectric points have been reported to precede development of microalbuminuria in patients who have diabetes mellitus with hypertension. We examined how hypertension affects these urinary proteins in a diabetic state. Excretion of IgG, ceruloplasmin, transferrin, albumin, α2-macroglobulin with a large molecular radius of 88 Å and N-acetylglucosaminidase in first-morning urine samples were measured in normoalbuminuric patients (urinary albumin-to-creatinine ratio hypertension and nondiabetes mellitus (group hypertension, n = 32), type 2 diabetes mellitus and normotension (group diabetes mellitus, n = 52) and type 2 diabetes mellitus and hypertension (group Both, n =45), and in age-matched controls (n = 72). Urinary IgG, ceruloplasmin, transferrin, albumin and N-acetylglucosaminidase and estimated glomerular filtration rate (eGFR) were significantly elevated in groups diabetes mellitus and Both compared with controls. Furthermore, urinary IgG, ceruloplasmin and transferrin in group Both were significantly higher than those in group diabetes mellitus. These exhibited a positive and relatively strong association with eGFR compared with controls. No significant difference in urinary albumin or N-acetylglucosaminidase was found between the two diabetic groups. In contrast, group hypertension had elevated urinary transferrin without any changes in the other compounds. Urinary α2-macroglobulin did not differ among the four groups. These findings suggest that normoalbuminuric diabetic patients without hypertension have both glomerular hemodynamic changes such as increased intraglomerular hydraulic pressure and altered proximal tubules, and that hypertension increases intraglomerular hydraulic pressure. Increased urinary IgG, ceruloplasmin and transferrin may reflect an increase in

  13. Transferrin coupled azanthraquinone enhances the killing effect on trypanosomes. The role of lysosomal mannosidase

    Directory of Open Access Journals (Sweden)

    Nok A.J.

    2002-12-01

    Full Text Available Partially purified azanthraquinone (AQ extract from Mitracarpus scaber was coupled to bovine transferrin (Tf using azidophenyl glyoxal (APG. The AQ-APG-Tf conjugate was found to possess an enhanced in vitro trypanocidal activity against Trypanosoma congolense and T. brucei brucei. At low concentrations of 0.39-90 mg/ml, the conjugate diminished the growth of T. congolense and T. b. brucei dose dependently at the logarithmic phase. Both parasites were more sensitive to AQ-APG-Tf than to the free (AQ extract. Growth inhibition on the parasites by the free extract was observed at 20-200 mg/ml. The total activity of the lysosomal enzyme a-mannosidase was reduced in the T. congolense cells treated with AQ-APG-Tf in a dose related pattern. However, the activity of the mannosidase in the T. b. brucei treated cells is less affected. The AQ-APG-Tf is more effective on a mannosidase than free AQ, eight and four fold for T. congolense and T. b. brucei respectively. The results are discussed as regards the potency of using transferrin as suitable drug carrier in the chemotherapy of Human sleeping sickness.

  14. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Seung Min, E-mail: smjeong@catholic.ac.kr [Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Hwang, Sunsook; Seong, Rho Hyun [School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2016-03-11

    The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

  15. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

    International Nuclear Information System (INIS)

    Jeong, Seung Min; Hwang, Sunsook; Seong, Rho Hyun

    2016-01-01

    The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

  16. Bioinformatics analysis for evaluation of the diagnostic potentialities of miR-19b, -125b and -205 as liquid biopsy markers of prostate cancer

    Science.gov (United States)

    Bryzgunova, O. E.; Lekchnov, E. A.; Zaripov, M. M.; Yurchenko, Yu. B.; Yarmoschuk, S. V.; Pashkovskaya, O. A.; Rykova, E. Yu.; Zheravin, A. A.; Laktionov, P. P.

    2017-09-01

    Presence of tumor-derived cell-free miRNA in biological fluids as well as simplicity and robustness of cell-free miRNA quantification makes them suitable markers for cancer diagnostics. Based on previously published data demonstrating diagnostic potentialities of miR-205 in blood and miR-19b as well as miR-125b in urine of prostate cancer patients, bioinformatics analysis was carried out to follow their involvement in prostate cancer development and select additional miRNA-markers for prostate cancer diagnostics. Studied miRNAs are involved in different signaling pathways and regulate a number of genes involved in cancer development. Five of their targets (CCND1, BRAF, CCNE1, CCNE2, RAF1), according to the STRING database, act as part of the same signaling pathway. RAF1 is regulated by miR-19b and miR-125b, and it was shown to be involved in prostate cancer development by DIANA and STRING databases. Thus, other microRNAs regulating RAF1 expression such as miR-16, -195, -497, and -7 (suggested by DIANA, TargetScan, MiRTarBase and miRDB databases) can potentially be regarded as prostate cancer markers.

  17. Coating Nanoparticles with Plant-Produced Transferrin-Hydrophobin Fusion Protein Enhances Their Uptake in Cancer Cells

    DEFF Research Database (Denmark)

    Reuter, Lauri J.; Shahbazi, Mohammad-Ali; Makila, Ermei M.

    2017-01-01

    can be expressed in Nicotiana benthamiana plants as a fusion with Trichoderma reesei hydrophobins HFBI, HFBII, or HFBIV. Transferrin-HFBIV was further expressed in tobacco BY-2 suspension cells. Both partners of the fusion protein retained their functionality; the hydrophobin moiety enabled migration...... to a surfactant phase in an aqueous two-phase system, and the transferrin moiety was able to reversibly bind iron. Coating porous silicon nanoparticles with the fusion protein resulted in uptake of the nanoparticles in human cancer cells. This study provides a proof-of concept for the functionalization...

  18. In-office diagnostic arthroscopy for knee and shoulder intra-articular injuries its potential impact on cost savings in the United States

    Science.gov (United States)

    2014-01-01

    Background The purpose of this analysis was to determine whether in office diagnostic needle arthroscopy (Visionscope Imaging System [VSI]) can provide for improved diagnostic assessment and; more cost effective care. Methods Data on arthroscopy procedures in the US for deep seated pathology in the knee and shoulder were used (Calendar Year 2012). These procedures represent approximately 25-30% of all arthroscopic procedures performed annually. Sensitivities, specificities, positive predictive, and negative predictive values for MRI analysis of this deep seated pathology from systematic reviews and meta-analyses were used in assessing for false positive and false negative MRI findings. The costs of performing diagnostic and surgical arthroscopy procedures (using 2013 Medicare reimbursement amounts); costs associated with false negative findings; and the costs for treating associated complications arising from diagnostic and therapeutic arthroscopy procedures were then assessed. Results In patients presenting with medial meniscal pathology (ICD9CM diagnosis 836.0 over 540,000 procedures in CY 2012); use of the VSI system in place of MRI assessment (standard of care) resulted in a net cost savings to the system of $151 million. In patients presenting with rotator cuff pathology (ICD9CM 840.4 over 165,000 procedures in CY2012); use of VSI in place of MRI similarly saved $59 million. These savings were realized along with more appropriate care as; fewer patients were exposed to higher risk surgical arthroscopic procedures. Conclusions The use of an in-office arthroscopy system can: possibly save the US healthcare system money; shorten the diagnostic odyssey for patients; potentially better prepare clinicians for arthroscopic surgery (when needed) and; eliminate unnecessary outpatient arthroscopy procedures, which commonly result in surgical intervention. PMID:24885678

  19. Influence of carbonate on the complexation of Cm(III) with human serum transferrin studied by time-resolved laser fluorescence spectroscopy (TRLFS)

    International Nuclear Information System (INIS)

    Bauer, Nicole; Panak, Petra J.

    2015-01-01

    The complexation of Cm(III) with transferrin is investigated in the pH range from 3.5 to 11.0 in the absence of carbonate and at c(carbonate)(tot) = 25 mM. In the absence of carbonate two Cm(III) transferrin species I and II are formed depending on pH. An increase of the total carbonate concentration favors the formation of the Cm(III) transferrin species II with Cm(III) bound at the Fe(III) binding site of transferrin at significantly lower pH values. The spectroscopic results directly prove that carbonate acts as a synergistic anion for Cm(III) complexation at the binding site of transferrin. At c(carbonate)(tot) = 25 mM the formation of the nonspecific Cm(III) transferrin species I is suppressed completely. Instead, three Cm(III) carbonate species Cm(CO 3 ) + , Cm(CO 3 ) 2 - and Cm(CO 3 ) 3 3- are formed successively with increasing pH. The formation of Cm(III) carbonate species results in a decreased fraction of the Cm(III) transferrin species II at pH ≥ 7.4 which indicates that carbonate complexation is an important competition reaction for Cm(III) transferrin complexation at physiological carbonate concentration. (authors)

  20. Targeting immunoliposomes to transferrin receptors on brain capillary endothelial cells as a mean for cargo transport across the blood-brain barrier

    DEFF Research Database (Denmark)

    Johnsen, Kasper Bendix; Larsen, Annette Burkhart; Bruun, Jonas

    2016-01-01

    Brain capillary endothelial cells (BCECs) express transferrin receptors as opposed to endothelial cells of any organ in the remaining body, suggesting that targeting to the transferrin receptors as a reasonable strategy for delivering drugs to the CNS. However, as the intracellular trafficking...

  1. Predicting C282Y Homozygote Genotype for Hemochromatosis Using Serum Ferritin and Transferrin Saturation Values from 44,809 Participants of the HEIRS Study

    Directory of Open Access Journals (Sweden)

    Andrew Lim

    2014-01-01

    Full Text Available INTRODUCTION: The simultaneous interpretation of serum ferritin level and transferrin saturation has been used as a clinical guide to diagnose genetic hemochromatosis. The Hemochromatosis and Iron Overload Screening (HEIRS Study screened 101,168 North American participants for serum ferritin level and transferrin saturation, and C282Y genotyping for the HFE gene.

  2. A direct indication of plasma potential diagnostic with fast time response and high accuracy based on a differential emissive probe

    International Nuclear Information System (INIS)

    Yao, W.E.; Hershkowitz; Intrator, T.

    1985-01-01

    The floating potential of the emissive probe has been used to directly measure the plasma potential. The authors have recently presented another method for directly indicating the plasma potential with a differential emissive probe. In this paper they describe the effects of probe size, plasma density and plasma potential fluctuation on plasma potential measurements and give methods for reducing errors. A control system with fast time response (α 20 μs) and high accuracy (the order of the probe temperature T/sub w//e) for maintaining a differential emissive probe at plasma potential has been developed. It can be operated in pulsed discharge plasma to measure plasma potential dynamic characteristics. A solid state optical coupler is employed to improve circuit performance. This system was tested experimentally by measuring the plasma potential in an argon plasma device an on the Phaedrus tandem mirror

  3. A direct indication of plasma potential diagnostic with fast time response and high accuracy based on a differential emissive probe

    International Nuclear Information System (INIS)

    Yao, W.E.; Hershkowitz, N.; Intrator, T.

    1985-01-01

    The floating potential of the emissive probe has been used to directly measure the plasma potential. The authors have recently presented another method for directly indicating the plasma potential with a differential emissive probe. In this paper they describe the effects of probe size, plasma density and plasma potential fluctuation on plasma potential measurements and give methods for reducing errors. A control system with fast time response (≅ 20 μs) and high accuracy (the order of the probe temperature T/sub w//e) for maintaining a differential emissive probe at plasma potential has been developed. It can be operated in pulsed discharge plasma to measure plasma potential dynamic characteristics. A solid state optical coupler is employed to improve circuit performance. This system was tested experimentally by measuring the plasma potential in an argon plasma device and on the Phaedrus tandem mirror

  4. PLASMA DIAGNOSTIC POTENTIAL OF 2p4f IN N{sup +}—ACCURATE WAVELENGTHS AND OSCILLATOR STRENGTHS

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Xiaozhi [School of Physics Science and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); Li, Jiguang; Wang, Jianguo [Data Center for High Energy Density Physics, Institute of Applied Physics and Computational Mathematics, P.O. Box 8009, Beijing 100088 (China); Jönsson, Per, E-mail: Li_Jiguang@iapcm.ac.cn [Materials Science and Applied Mathematics, Malmö University, SE-20506 Malmö (Sweden)

    2015-03-10

    Radiative emission lines from nitrogen and its ions are often observed in nebula spectra, where the N{sup 2+} abundance can be inferred from lines of the 2p4f configuration. In addition, intensity ratios between lines of the 2p3p-2p3s and 2p4f-2p3d transition arrays can serve as temperature diagnostics. To aid abundance determinations and plasma diagnostics, wavelengths and oscillator strengths were calculated with high precision for electric dipole (E1) transitions from levels in the 2p4f configuration of N{sup +}. Electron correlation and relativistic effects, including the Breit interaction, were systematically taken into account within the framework of the multiconfiguration Dirac-Hartree-Fock method. Except for the 2p4f-2p4d transitions with quite large wavelengths and the two-electron-one-photon 2p4f-2s2p {sup 3} transitions, the uncertainties of the present calculations were controlled to within 3% and 5% for wavelengths and oscillator strengths, respectively. We also compared our results with other theoretical and experimental values when available. Discrepancies were found between our calculations and previous calculations due to the neglect of relativistic effects in the latter.

  5. Screening for transfusion transmissible infections using rapid diagnostic tests in Africa: a potential hazard to blood safety?

    Science.gov (United States)

    Prugger, C.; Laperche, S.; Murphy, E. L.; Bloch, E. M.; Kaidarova, Z.; Tafflet, M.; Lefrère, J.-J.; Jouven, X.

    2016-01-01

    Rapid diagnostic tests (RDTs) are routinely used in African blood centres. We analysed data from two cross-sectional studies representing 95 blood centres in 29 African countries. Standardized panels of sera containing varying concentrations of anti-human immunodeficiency virus (HIV) antibodies (Ab), hepatitis B virus antigen (HBsAg) and antihepatitis C virus (HCV) Ab were screened using routine operational testing procedures at the centres. Sensitivity of detection using RDTs was high for HIV Ab-positive samples, but low for intermediately HBsAg (51·5%) and HCV Ab (40·6%)-positive samples. These findings suggest that current RDT use in Africa could pose a hazard to blood safety. PMID:26646317

  6. Circulating miR-765 and miR-149: Potential Noninvasive Diagnostic Biomarkers for Geriatric Coronary Artery Disease Patients

    Directory of Open Access Journals (Sweden)

    Md Sayed Ali Sheikh

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the diagnostic value of circulating miR-765 and miR-149 as noninvasive early biomarkers for geriatric coronary artery disease (CAD patients. A total of 69 angiographically documented CAD patients including 37 stable CAD (72.9 ± 4.2 years and 32 unstable CAD (72.03 ± 4.3 years and 20 healthy subjects (71.7 ± 5.2 years, matched for age, sex, smoking habit, hypertension, and diabetes, were enrolled in this study. Compared with healthy subjects, circulating miR-765 levels were increased by 2.9-fold in stable CAD and 5.8-fold in unstable CAD patients, respectively, while circulating miR-149 levels were downregulated by 3.5-fold in stable CAD and 4.2-fold in unstable CAD patients, respectively. Furthermore, plasma levels of miR-765 were found to be positively correlated with ages within control, stable, and unstable groups. The ROC curves of miR-765 and miR-149 represented significant diagnostic values with an area under curve (AUC of 0.959, 0.972 and 0.938, 0.977 in stable CAD patients and unstable CAD patients as compared with healthy subjects, respectively. Plasma levels of miR-765 and miR-149 might be used as noninvasive biomarkers for the diagnosis of CAD in geriatric people.

  7. Benefits of a European project on diagnostics of highly pathogenic agents and assessment of potential dual use issues

    Directory of Open Access Journals (Sweden)

    Roland eGrunow

    2014-11-01

    Full Text Available R. Grunow1 (Coordinator, G. Ippolito2 (Co-Coordinator, D. Jacob1, U. Sauer1, A. Rohleder1, A. Di Caro2, R. Iacovino2, and on behalf of the QUANDHIP partners31-Robert Koch Institute, Berlin, Germany; 2- L. Spallanzani National Institute for Infectious Diseases, Rome, Italy; 3- http://www.quandhip.info/Quandhip/EN/Home/Homepage_node.htmlQUANDHIP (Quality Assurance Exercises and Networking on the Detection of Highly Infectious Pathogens is a Joint Action initiative set up in 2011 that has successfully unified the primary objectives of the European Networks on Highly Pathogenic Bacteria (ENHPB and of P4 laboratories (ENP4 both of which aimed to improve the efficiency, effectiveness and response capabilities of laboratories directed at protecting the health of European citizens against high consequence bacteria and viruses of significant public health concern. Both networks have established a common collaborative consortium of 37 nationally and internationally recognized institutions with laboratory facilities from 22 European countries.The specific objectives and achievements include the initiation and establishment of-a recognized and acceptable quality assurance scheme, including practical External Quality Assurance Exercises, comprising living agents, that aim to improve laboratory performance, accuracy and detection capabilities in support of patient management and public health responses.-recognized training schemes for diagnostics and handling of highly pathogenic agents-an international repository comprising highly pathogenic bacteria and viruses for the development of standardized reference material-a standardized and transparent biosafety and biosecurity strategy safeguarding healthcare personnel and the community in dealing with high consequence pathogens-the design and organisation of response capabilities dealing with cross border events with highly infectious pathogens including the consideration of diagnostic capabilities of European

  8. Transferrin receptor molecular imaging: targeting for diagnosis and monitoring of gene delivery

    International Nuclear Information System (INIS)

    Eun-Mi Kim; Hwan-Jeong Jeong; Jin-Hee Kim; Chang-Guhn Kim

    2004-01-01

    Tc labeled complexes in the tumor two days after administration was visualized fluorescence microscope. Conclusion: Using 99mTc transferrin conjugate, transferrin binding to transferrin receptor on tumor cell could be seen in vivo. Also we certificated the possibility of monitoring whether the Tf-dendrimer gene complex is delivered to the desirous site. (authors)

  9. Kinetic, spectroscopic and chemical modification study of iron release from transferrin; iron(III) complexation to adenosine triphosphate

    International Nuclear Information System (INIS)

    Thompson, C.P.

    1985-01-01

    Amino acids other than those that serve as ligands have been found to influence the chemical properties of transferrin iron. The catalytic ability of pyrophosphate to mediate transferrin iron release to a terminal acceptor is largely quenched by modification non-liganded histine groups on the protein. The first order rate constants of iron release for several partially histidine modified protein samples were measured. A statistical method was employed to establish that one non-liganded histidine per metal binding domain was responsible for the reduction in rate constant. These results imply that the iron mediated chelator, pyrophosphate, binds directly to a histidine residue on the protein during the iron release process. EPR spectroscopic results are consistent with this interpretation. Kinetic and amino acid sequence studies of ovotransferrin and lactoferrin, in addition to human serum transferrin, have allowed the tentative assignment of His-207 in the N-terminal domain and His-535 in the C-terminal domain as the groups responsible for the reduction in rate of iron release. The above concepts have been extended to lysine modified transferrin. Complexation of iron(II) to adenosine triphosphate (ATP) was also studied to gain insight into the nature of iron-ATP species present at physiological pH. 31 P NMR spectra are observed when ATP is presented in large excess

  10. 67Ga in transferrin-unbound form is taken up by inflamed liver of mouse treated with CCl4

    International Nuclear Information System (INIS)

    Ohkubo, Yasuhito; Sasayama, Akio; Takegahara, Ikumi; Katoh, Shinsuke; Abe, Kenichi; Kohno, Hiroyuki; Kubodera, Akiko.

    1990-01-01

    In order to investigate whether or not transferrin is involved in the uptake of 67 Ga by inflamed liver (acute inflammatory tissues) the uptake of 67 Ga by the liver of mice treated with carbon tetrachloride (CCl 4 ) was studied. The serum GPT value reached its maximum on the 1st day after the CCl 4 treatment. The uptake of 67 Ga by the liver also reached its maximum on the 1st day after the CCl-4 treatment and the amount uptake into inflamed liver was about 6 times that uptaken into normal liver. On the other hand, the uptake of 125 I-transferrin into inflamed liver on the 1st day after CCl 4 treatment was only about 1.6 times that into normal liver. Moreover, cold Fe 3+ decreased the uptake of 67 Ga by normal liver but increased the uptake of 67 Ga by inflamed liver. These results show that transferrin plays an important role in the uptake of 67 Ga by normal liver but not by inflamed liver, i.e. 67 Ga in the transferrin-unbound form is preferentially taken up by inflamed liver. (author)

  11. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse

    Science.gov (United States)

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  12. Arf6, Rab11 and transferrin receptor define distinct populations of recycling endosomes.

    Science.gov (United States)

    Kobayashi, Hotaka; Fukuda, Mitsunori

    2013-09-01

    Recycling endosomes are key platforms for endocytic recycling that return internalized molecules back to the plasma membrane. To determine how recycling endosomes perform their functions, searching for proteins and lipids that specifically localized at recycling endosomes has often been performed by colocalization analyses between candidate molecules and conventional recycling endosome markers. However, it remains unclear whether all the conventional markers have identical localizations. Here we report finding that three well-known recycling endosome markers, i.e., Arf6, Rab11 and transferrin receptor (TfR), have different intracellular localizations in PC12 cells. The results of immunofluorescence analyses showed that the signals of endogenous Arf6, Rab11 and TfR in nerve growth factor-stimulated PC12 cells generally differed, although there was some overlapping. Our findings provide new information about recycling endosome markers, and they highlight the heterogeneity of recycling endosomes.

  13. Transferrin Sialylation in Smoking and Non-Smoking Pregnant Women with Intrauterine Growth Restriction.

    Science.gov (United States)

    Wrześniak, Marta; Kepinska, Marta; Bizoń, Anna; Milnerowicz-Nabzdyk, Ewa; Milnerowicz, Halina

    2015-01-01

    Transferrin (Tf) is a glycosylated protein responsible for transporting iron. Various sialylation levels of Tf are observed during physiological and pathological processes. We studied if the changes in iron stores as well as tobacco smoke may have an impact on foetal development and in consequence lead to intrauterine growth restriction (IUGR). In the third trimester of pregnancy, lower levels of 4-sialoTf isoform and higher levels of 5-sialoTf were observed in the serum of non-smoking women with IUGR in comparison to the control group. On the day of labour, level of 2-sialoTf was significantly lower and level of 3-sialo was Tf higher in the serum of non-smoking women. Level of 4-sialo was found lower in the serum of smoking women with IUGR than in the control group. The observed changes may suggest a connection between iron stores, transport of iron to the foetus and foetal development.

  14. Potentialities of aberrantly methylated circulating DNA for diagnostics and post-treatment follow-up of lung cancer patients.

    Science.gov (United States)

    Ponomaryova, Anastasia A; Rykova, Elena Yu; Cherdyntseva, Nadezda V; Skvortsova, Tatiana E; Dobrodeev, Alexey Yu; Zav'yalov, Alexander A; Bryzgalov, Leonid O; Tuzikov, Sergey A; Vlassov, Valentin V; Laktionov, Pavel P

    2013-09-01

    To date, aberrant DNA methylation has been shown to be one of the most common and early causes of malignant cell transformation and tumors of different localizations, including lung cancer. Cancer cell-specific methylated DNA has been found in the blood of cancer patients, indicating that cell-free DNA circulating in the blood (cirDNA) is a convenient tumor-associated DNA marker that can be used as a minimally invasive diagnostic test. In the current study, we investigated the methylation status in blood samples of 32 healthy donors and 60 lung cancer patients before and after treatment with neoadjuvant chemotherapy followed by total tumor resection. Using quantitative methylation-specific PCR, we found that the index of methylation (IM), calculated as IM = 100 × [copy number of methylated/(copy number of methylated + unmethylated gene)], for the RASSF1A and RARB2 genes in the cirDNA isolated from blood plasma and cell-surface-bound cirDNA was elevated 2- to 3-fold in lung cancer patients compared with healthy donors. Random forest classification tree model based on these variables combined (RARB2 and RASSF1A IM in both plasma and cell-surface-bound cirDNA) lead to NSCLC patients' and healthy subjects' differentiation with 87% sensitivity and 75% specificity. An association of increased IM values with an advanced stage of non-small-cell lung cancer was found for RARB2 but not for RASSF1A. Chemotherapy and total tumor resection resulted in a significant decrease in the IM for RARB2 and RASSF1A, in both cirDNA fractions, comparable to the IM level of healthy subjects. Importantly, a rise in the IM for RARB2 was detected in patients within the follow-up period, which manifested in disease relapse at 9 months, confirmed with instrumental and pathologic methods. Our data indicate that quantitative analysis of the methylation status of the RARB2 and RASSF1A tumor suppressor genes in both cirDNA fractions is a useful tool for lung cancer diagnostics, evaluation of cancer

  15. Endocytosis of a functionally enhanced GFP-tagged transferrin receptor in CHO cells.

    Directory of Open Access Journals (Sweden)

    Qi He

    Full Text Available The endocytosis of transferrin receptor (TfR has served as a model to study the receptor-targeted cargo delivery system for cancer therapy for many years. To accurately evaluate and optically measure this TfR targeting delivery in vitro, a CHO cell line with enhanced green fluorescent protein (EGFP-tagged human TfR was established. A chimera of the hTfR and EGFP was engineered by fusing EGFP to the amino terminus of hTfR. Data were provided to demonstrate that hTfR-EGFP chimera was predominantly localized on the plasma membrane with some intracellular fluorescent structures on CHO cells and the EGFP moiety did not affect the endocytosis property of hTfR. Receptor internalization occurred similarly to that of HepG2 cells expressing wild-type hTfR. The internalization percentage of this chimeric receptor was about 81 ± 3% of wild type. Time-dependent co-localization of hTfR-EGFP and PE-conjugated anti-hTfR mAb in living cells demonstrated the trafficking of mAb-receptor complexes through the endosomes followed by segregation of part of the mAb and receptor at the late stages of endocytosis. The CHO-hTfR cells preferentially took up anti-hTfR mAb conjugated nanoparticles. This CHO-hTfR cell line makes it feasible for accurate evaluation and visualization of intracellular trafficking of therapeutic agents conjugated with transferrin or Abs targeting the hTfRs.

  16. Enhanced expression of transferrin receptor confers UV-resistance in human and monkey cells

    International Nuclear Information System (INIS)

    Chen, Zheng; Nomura, Jun; Suzuki, Toshikazu; Suzuki, Nobuo

    2005-01-01

    One of the most intriguing biological subjects is cell-surface molecules that regulate the susceptibility of human cells to cell-killing effects after irradiation with far-ultraviolet light (UV, principally 254 nm wavelength). Human RSa cells have unusual sensitivity to UV-induced cell-killing. We searched for molecules on the cell-surface of RSa cells that were present in different amounts as compared to a variant of these cells, UV r -1 cells, which have increased resistance to UV cell-killing. Among the 21 molecules examined, the amount of transferrin receptor (TfR) protein was found to be 2-fold higher in UV r -1 cells compared with in RSa cells. The amounts of this protein were also higher in the UV-resistant hematopoietic cell lines, CEM6 and Daudi, as compared to the UV-sensitive cell lines, Molt4 and 697. Culturing of UV r -1 cells in a medium containing anti-transferrin antibodies resulted in sensitization of the cells to UV cell-killing as demonstrated by colony formation assay. Similar results were observed by treatment of the cells with TfR siRNA. In contrast, overexpression of TfR protein led to a resistance to UV cell-killing in RSa cells and monkey COS7 cells as demonstrated by both colony formation and apoptosis assay. In TfR-overexpressing cells, reduction of p53 and Bax protein was observed after UV-irradiation. Thus, TfR expression appears to be involved in the regulation of UV-resistance, possibly via modulation of the amount of p53 and Bax protein. (author)

  17. Advanced gestational age increases serum carbohydrate-deficient transferrin levels in abstinent pregnant women.

    Science.gov (United States)

    Bakhireva, Ludmila N; Cano, Sandra; Rayburn, William F; Savich, Renate D; Leeman, Lawrence; Anton, Raymond F; Savage, Daniel D

    2012-01-01

    Carbohydrate-deficient transferrin (%CDT) is a well-established and highly specific biomarker for sustained heavy consumption of alcohol. However, in pregnant women, the specificity of this biomarker might be affected by advanced gestational age, even after accounting for increased transferrin concentrations in pregnancy. The goal of this prospective study was to assess the variability in %CDT during pregnancy among alcohol-abstaining patients. Patients were recruited during one of the first prenatal care visits and followed-up to term. Abstinence was confirmed by maternal self-report and by alcohol biomarkers. Biomarkers assessed in the mother included serum gamma-glutamyltranspeptidase, urine ethyl glucuronide and ethyl sulfate, and whole blood phosphatidylethanol (PEth). In addition, PEth was measured in a dry blood spot card obtained from a newborn. For %CDT analysis, serum samples were collected at baseline and at term and analyzed by an internationally validated high-performance liquid chromatography and spectrophotometric detection method. At recruitment (mean gestational age 22.6 ± 7.3 weeks), the mean %CDT concentration was 1.49 ± 0.30%, while at term, it increased to 1.67 ± 0.28% (P = 0.001). Using a conventional cutoff concentration %CDT >1.7%, 22.9 and 45.7% of the sample would be classified as 'positive' for this biomarker at recruitment and at term, respectively (P = 0.011 ). These results suggest that a conventional cutoff of 1.7% might be too low for pregnant women and would generate false-positive results. We propose that %CDT >2.0% be used as a cutoff concentration indicative of alcohol exposure in pregnant women. The sensitivity of %CDT at this cutoff for heavy drinking during pregnancy needs to be assessed further.

  18. Potential diagnostic value of regional myocardial adrenergic imaging using {sup 123}I-MIBG SPECT to identify patients with Lewy body diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lebasnier, Adrien; Peyronnet, Damien; Bouvard, Gerard [University Hospital Center of Caen, Department of Nuclear Medicine, Caen (France); Lamotte, Guillaume; Defer, Gilles [University Hospital Center of Caen, Department of Neurology, Caen (France); Manrique, Alain [University Hospital Center of Caen, Department of Nuclear Medicine, Caen (France); Cyceron PET Centre, Caen (France); Normandie Universite, Caen (France); Agostini, Denis [University Hospital Center of Caen, Department of Nuclear Medicine, Caen (France); Normandie Universite, Caen (France)

    2015-01-28

    The aim of this study was to determine the potential diagnostic value of regional myocardial adrenergic {sup 123}I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) imaging to identify patients with Lewy body diseases (LBD+). Sixty-four consecutive patients who underwent cardiac {sup 123}I-MIBG SPECT to differentiate LBD+, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB), from patients without LBD (LBD-) were retrospectively reviewed. A neurologist expert in memory disorders determined the final clinical diagnosis by using international clinical diagnostic criteria. Planar [heart to mediastinum ratio (HMR)] and {sup 123}I-MIBG SPECT[innervation defect score (IDS)] using the 17-segment left ventricular model (five-point scale) were obtained 4 h after the injection of {sup 123}I-MIBG on a low-energy high-resolution (LEHR) collimator. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal HMR and IDS cut-off values to discriminate LBD+ from LBD-. Of the 64 patients, 45 (70 %) were diagnosed LBD+ (DLB, n = 27; PD, n = 18) and 19 were diagnosed LBD- (5 other dementias, 14 other parkinsonisms). The HMR and IDS of LBD+ were significantly different from those of LBD- (1.30 ± 0.21 vs 1.65 ± 0.26, p < 0.001; 39 ± 28 vs 8 ± 16, p = 0.001). The optimal HMR and IDS cut-off values to discriminate LBD+ (n = 45) from LBD- (n = 19) were 1.47 and 6/68, providing a sensitivity and specificity of 82.2 and 84.2 % and 86.7 and 73.7 %, respectively. Regional myocardial adrenergic {sup 123}I-MIBG imaging SPECT has a potential diagnostic value to identify LBD+. (orig.)

  19. Diagnostic and prognostic potential of serum miR-132/212 cluster in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Feng; Wang, Jun; Ju, Linlin; Chen, Lin; Cai, Weihua; Yang, Jialin

    2018-01-01

    Background It has been reported that both of the miR-132/212 (micro-RNA) cluster members, miR-132 and miR-212, are downregulated in hepatocellular carcinoma. Nevertheless, the expression pattern and clinical utility of serum miR-132/212 in hepatocellular carcinoma are still unknown. Methods In this study, serum concentrations of miR-132 and miR-212 were measured in 80 hepatocellular carcinoma patients, 51 controls with chronic liver diseases and 42 healthy volunteers by using quantitative real-time polymerase chain reaction. Results In hepatocellular carcinoma patients, serum concentrations of miR-132 and miR-212 were significantly reduced and strongly correlated (r = 0.603, p hepatocellular carcinoma. Moreover, the combination of serum miR-132, miR-212 and alpha-fetoprotein improved the diagnostic efficiency for hepatocellular carcinoma, especially in sensitivity and negative predictive value. Serum miR-132 was associated with tumour differentiation degree ( p = 0.021) and tumour-node-metastasis stage ( p = 0.002); serum miR-212 correlated with tumour size ( p = 0.023) and tumour-node-metastasis stage ( p = 0.007). Kaplan-Meier analyses indicated poorer overall survival in hepatocellular carcinoma patients with lower serum concentrations of miR-132 ( p hepatocellular carcinoma.

  20. A potential new diagnostic tool to aid DNA analysis from heat compromised bone using colorimetry: A preliminary study.

    Science.gov (United States)

    Fredericks, Jamie D; Ringrose, Trevor J; Dicken, Anthony; Williams, Anna; Bennett, Phil

    2015-03-01

    Extracting viable DNA from many forensic sample types can be very challenging, as environmental conditions may be far from optimal with regard to DNA preservation. Consequently, skeletal tissue can often be an invaluable source of DNA. The bone matrix provides a hardened material that encapsulates DNA, acting as a barrier to environmental insults that would otherwise be detrimental to its integrity. However, like all forensic samples, DNA in bone can still become degraded in extreme conditions, such as intense heat. Extracting DNA from bone can be laborious and time-consuming. Thus, a lot of time and money can be wasted processing samples that do not ultimately yield viable DNA. We describe the use of colorimetry as a novel diagnostic tool that can assist DNA analysis from heat-treated bone. This study focuses on characterizing changes in the material and physical properties of heated bone, and their correlation with digitally measured color variation. The results demonstrate that the color of bone, which serves as an indicator of the chemical processes that have occurred, can be correlated with the success or failure of subsequent DNA amplification. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

  1. CpG Methylation Analysis—Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics

    Science.gov (United States)

    Sepulveda, Antonia R.; Jones, Dan; Ogino, Shuji; Samowitz, Wade; Gulley, Margaret L.; Edwards, Robin; Levenson, Victor; Pratt, Victoria M.; Yang, Bin; Nafa, Khedoudja; Yan, Liying; Vitazka, Patrick

    2009-01-01

    Methylation of CpG islands in gene promoter regions is a major molecular mechanism of gene silencing and underlies both cancer development and progression. In molecular oncology, testing for the CpG methylation of tissue DNA has emerged as a clinically useful tool for tumor detection, outcome prediction, and treatment selection, as well as for assessing the efficacy of treatment with the use of demethylating agents and monitoring for tumor recurrence. In addition, because CpG methylation occurs early in pre-neoplastic tissues, methylation tests may be useful as markers of cancer risk in patients with either infectious or inflammatory conditions. The Methylation Working Group of the Clinical Practice Committee of the Association of Molecular Pathology has reviewed the current state of clinical testing in this area. We report here our summary of both the advantages and disadvantages of various methods, as well as the needs for standardization and reporting. We then conclude by summarizing the most promising areas for future clinical testing in cancer molecular diagnostics. PMID:19541921

  2. Characterizing the intrinsic bioremediation potential of 1,4-dioxane and trichloroethene using innovative environmental diagnostic tools.

    Science.gov (United States)

    Chiang, Sheau-Yun Dora; Mora, Rebecca; Diguiseppi, William H; Davis, Greg; Sublette, Kerry; Gedalanga, Phillip; Mahendra, Shaily

    2012-09-01

    An intrinsic biodegradation study involving the design and implementation of innovative environmental diagnostic tools was conducted to evaluate whether monitored natural attenuation (MNA) could be considered as part of the remedial strategy to treat an aerobic aquifer contaminated with 1,4-dioxane and trichloroethene (TCE). In this study, advanced molecular biological and stable isotopic tools were applied to confirm in situ intrinsic biodegradation of 1,4-dioxane and TCE. Analyses of Bio-Trap® samplers and groundwater samples collected from monitoring wells verified the abundance of bacteria and enzymes capable of aerobically degrading TCE and 1,4-dioxane. Furthermore, phospholipid fatty acid analysis with stable isotope probes (PLFA-SIP) of the microbial community validated the ability for microbial degradation of TCE and 1,4-dioxane. Compound specific isotope analysis (CSIA) of groundwater samples for TCE resulted in δ(13)C values that indicated likely biodegradation of TCE in three of the four monitoring wells sampled. Results of the MNA evaluation showed that enzymes capable of aerobically degrading TCE and 1,4-dioxane were present, abundant, and active in the aquifer. Taken together, these results provide direct evidence of the occurrence of TCE and 1,4-dioxane biodegradation at the study site, supporting the selection of MNA as part of the final remedy at some point in the future.

  3. 4D co-registration of X-ray and MR-mammograms: initial clinical results and potential incremental diagnostic value.

    Science.gov (United States)

    Dietzel, Matthias; Hopp, Torsten; Ruiter, Nicole V; Kaiser, Clemens G; Kaiser, Werner A; Baltzer, Pascal A

    2015-01-01

    4D co-registration of X-ray- and MR-mammograms (XM and MM) is a new method of image fusion. The present study aims to evaluate its clinical feasibility, radiological accuracy, and potential clinical value. XM and MM of 25 patients were co-registered. Results were evaluated by a blinded reader. Precision of the 4D co-registration was "very good" (mean-score [ms]=7), and lesions were "easier to delineate" (ms=5). In 88.8%, "relevant additional diagnostic information" was present, accounting for a more "confident diagnosis" in 76% (ms=5). 4D co-registration is feasible, accurate, and of potential clinical value. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Plasma-potential diagnostic (PPD) hardware used on the Tandem Mirror Experiment-Upgrade (TMX-U)

    International Nuclear Information System (INIS)

    Steele, D.L.; Hornady, R.S.; Stever, R.D.; Coutts, G.W.; Nelson, D.H.

    1985-01-01

    The PPD is an instrument used to indirectly measure the potential of the center-cell plasma of TMX-U. Thallium ions are injected at energies of about 60 keV from an ion gun capable of 80 kV operation. The singly charged ions collide with plasma electrons and generate double-charged ions. Ions in the higher charge state exit the plasma and are detected in an electrostatic energy analyzer. From measurements of the injected ion energy and the output ion energy one can determine the plasma potential in the ionization region. The absolute potential measurements required careful calibrations of the energy analyzer. Hardware and techniques for calibration of the energy analyzer are discussed. 2 refs., 4 figs

  5. Circulating Plasma Levels of MicroRNA-21 and MicroRNA-221 Are Potential Diagnostic Markers for Primary Intrahepatic Cholangiocarcinoma

    Science.gov (United States)

    Kemeny, Nancy; Kingham, T. Peter; Allen, Peter J.; D’Angelica, Michael I.; DeMatteo, Ronald P.; Betel, Doron; Klimstra, David; Jarnagin, William R.; Ventura, Andrea

    2016-01-01

    Background MicroRNAs (miRNAs) are potential biomarkers in various malignancies. We aim to characterize miRNA expression in intrahepatic cholangiocarcinoma (ICC) and identify circulating plasma miRNAs with potential diagnostic and prognostic utility. Methods Using deep-sequencing techniques, miRNA expression between tumor samples and non-neoplastic liver parenchyma were compared. Overexpressed miRNAs were measured in plasma from an independent cohort of patients with cholangiocarcinoma using RT-qPCR and compared with that healthy volunteers. The discriminatory ability of the evaluated plasma miRNAs between patients and controls was evaluated with receiving operating characteristic (ROC) curves. Results Small RNAs from 12 ICC and 11 tumor-free liver samples were evaluated. Unsupervised hierarchical clustering using the miRNA expression data showed clear grouping of ICC vs. non-neoplastic liver parenchyma. We identified 134 down-regulated and 128 upregulated miRNAs. Based on overexpression and high fold-change, miR21, miR200b, miR221, and miR34c were measured in plasma from an independent cohort of patients with ICC (n = 25) and healthy controls (n = 7). Significant overexpression of miR-21 and miR-221 was found in plasma from ICC patients. Furthermore, circulating miR-21 demonstrated a high discriminatory ability between patients with ICC and healthy controls (AUC: 0.94). Conclusion Among the differentially expressed miRNAs in ICC, miR-21 and miR-221 are overexpressed and detectable in the circulation. Plasma expression levels of these miRNAs, particularly miR-21, accurately differentiates patients with ICC from healthy controls and could potentially serve as adjuncts in diagnosis. Prospective validation and comparison with other hepatobiliary malignancies is required to establish their potential role as diagnostic and prognostic biomarkers. PMID:27685844

  6. Performance of a commercial Chicken-Ovo-transferrin-ELISA on the serum of brown layer chickens infected with Gallibacterium anatis and Streptococcus zooepidemicus.

    Science.gov (United States)

    Roy, Krisna; Kjelgaard-Hansen, Mads; Pors, Susanne Elisabeth; Christensen, Jens Peter; Biswas, Paritosh Kumar; Bojesen, Anders Miki

    2014-01-01

    To evaluate Ovo-transferrin (OTF), a positive acute-phase protein in chickens, as a diagnostic biomarker of selected bacterial infections we checked the performance of a commercial Chicken-OTF-ELISA (ICL, Inc., Portland, OR, USA) by analytical and overlap performances using two groups of serum samples obtained from 26 Gallibacterium anatis-infected and 20 Streptococcus zooepidemicus-infected brown layer chickens. In addition, sera from 14 apparently healthy and 19 negative control chickens were analysed in the Gallibacterium group whereas sera from 20 healthy and 11 negative control chickens from the Streptococcus group were analysed. All calibration curves revealed high coefficients of determination (≥ 0.97) between optical density (OD 450nm) and concentrations of OTF (mg/ml). OTF concentrations in high, medium and low pools (made of sera from a combination of infected and/or non-infected birds) were >6.4, >3.8 to 6.7, >3.5 to chickens (Gallibacterium, 4.4 ± 0.3 mg/ml; Streptococcus, 3.2 ± 0.4 mg/ml) compared with negative controls (1.7 ± 0.1 mg/ml) (P Chicken-OTF-ELISA can be used to measure reproducible serum OTF concentrations in brown layer chickens as a response to G. anatis infections, whereas an adjustment of dilution process is proposed to optimize to use in S. zooepidemicus-infected chickens.

  7. The use of Na+ and K+ ion concentrations as potential diagnostic indicators of subclinical mastitis in dairy cows

    Directory of Open Access Journals (Sweden)

    Abdul Wahid Haron

    2014-11-01

    can be of immense diagnostic benefit and will compliments detection using CMT alone.

  8. LEVELS OF PATIENTS EXPOSURE AND A POTENTIAL FOR OPTIMIZATION OF THE PET DIAGNOSTICS IN THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    L. A. Chipiga

    2017-01-01

    examinations in Russia and for the intercomparison of results obtained in different positron emission tomography departments. Low dose computed tomography protocols, justification of diagnostic and multiphase computed tomography protocols, application of tube current modulation system and modern reconstruction algorithms, education and training of the staff in the field of radiation protection should be used for optimization of radiation protection of patient. 

  9. Automated single-trial assessment of laser-evoked potentials as an objective functional diagnostic tool for the nociceptive system.

    Science.gov (United States)

    Hatem, S M; Hu, L; Ragé, M; Gierasimowicz, A; Plaghki, L; Bouhassira, D; Attal, N; Iannetti, G D; Mouraux, A

    2012-12-01

    To assess the clinical usefulness of an automated analysis of event-related potentials (ERPs). Nociceptive laser-evoked potentials (LEPs) and non-nociceptive somatosensory electrically-evoked potentials (SEPs) were recorded in 37 patients with syringomyelia and 21 controls. LEP and SEP peak amplitudes and latencies were estimated using a single-trial automated approach based on time-frequency wavelet filtering and multiple linear regression, as well as a conventional approach based on visual inspection. The amplitudes and latencies of normal and abnormal LEP and SEP peaks were identified reliably using both approaches, with similar sensitivity and specificity. Because the automated approach provided an unbiased solution to account for average waveforms where no ERP could be identified visually, it revealed significant differences between patients and controls that were not revealed using the visual approach. The automated analysis of ERPs characterized reliably and objectively LEP and SEP waveforms in patients. The automated single-trial analysis can be used to characterize normal and abnormal ERPs with a similar sensitivity and specificity as visual inspection. While this does not justify its use in a routine clinical setting, the technique could be useful to avoid observer-dependent biases in clinical research. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Comparison of the Diagnostic Accuracy of the MSLN Gene Products, Mesothelin and Megakaryocyte Potentiating Factor, as Biomarkers for Mesothelioma in Pleural Effusions and Serum

    Directory of Open Access Journals (Sweden)

    Jenette Creaney

    2013-01-01

    Full Text Available The MSLN gene products, soluble mesothelin and megakaryocyte potentiating factor (MPF, are being investigated as biomarkers for the asbestos-related cancer malignant mesothelioma (MM. Pleural fluid biomarkers of MM can be elevated when serum levels remain normal. The aim of this study was to determine if this was true for MPF and to compare levels of mesothelin. Biomarker concentrations were compared in 66 MM patients, 39 patients with other malignancies, 37 with benign disease, 18 asbestos-exposed healthy individuals, and 53 patients with chronic kidney disease. In pleural effusions, MPF and soluble mesothelin concentrations were both significantly elevated in MM patients relative to controls. No significant difference between the area under the receiver operator curve (AUC for MPF (0.945±0.02 and mesothelin (0.928±0.03 when distinguishing MM from all other causes of effusion was observed. MPF and mesothelin serum concentrations were highly correlated and of equivalent diagnostic accuracy with AUCs of 0.813±0.04 and 0.829±0.03, respectively. Serum levels of both markers increased with decreasing kidney function. In conclusion, MPF is elevated in the pleural effusions of MM patients similar to that of mesothelin. Mesothelin and MPF convey equivalent diagnostic information for distinguishing MM from other diseases in pleural effusions as well as serum.

  11. Plasma-Potential Diagnostic (PPD) hardware used on the Tandem Mirror Experiment-Upgrade (TMX-U)

    International Nuclear Information System (INIS)

    Steele, D.L.; Hornady, R.S.; Stever, R.D.; Coutts, G.W.; Nelson, D.H.

    1986-01-01

    The PPD is an instrument used to indirectly measure the potential of the center-cell plasma of TMX-U. Thallium ions are injected at energies of about 60 keV from an ion gun capable of 80 kV operation. The singly charged ions collide with plasma electrons and generate double-charged ions. Ions in the higher charge state exit the plasma and are detected in an electrostatic energy analyzer. From measurements of the injected ion energy and the output ion energy one can determine the plasma potential in the ionization region. This paper discusses hardware and techniques for calibrating the energy analyzer on the PPD. Initially, calibrating the PPD analyzer required full operation of the TMX-U magnets to deflect the beam into the energy analyzer. Since it is a hazard to operate the magnets while personnel are in the pit area, calibration was done remotely. This was not only time consuming but also required magnet system operation personnel

  12. Shielding requirements for constant-potential diagnostic x-ray beams determined by a Monte Carlo calculation

    International Nuclear Information System (INIS)

    Simpkin, D.J.

    1989-01-01

    A Monte Carlo calculation has been performed to determine the transmission of broad constant-potential x-ray beams through Pb, concrete, gypsum wallboard, steel and plate glass. The EGS4 code system was used with a simple broad-beam geometric model to generate exposure transmission curves for published 70, 100, 120 and 140-kVcp x-ray spectra. These curves are compared to measured three-phase generated x-ray transmission data in the literature and found to be reasonable. For calculation ease the data are fit to an equation previously shown to describe such curves quite well. These calculated transmission data are then used to create three-phase shielding tables for Pb and concrete, as well as other materials not available in Report No. 49 of the NCRP

  13. Shielding requirements for constant-potential diagnostic x-ray beams determined by a Monte Carlo calculation.

    Science.gov (United States)

    Simpkin, D J

    1989-02-01

    A Monte Carlo calculation has been performed to determine the transmission of broad constant-potential x-ray beams through Pb, concrete, gypsum wallboard, steel and plate glass. The EGS4 code system was used with a simple broad-beam geometric model to generate exposure transmission curves for published 70, 100, 120 and 140-kVcp x-ray spectra. These curves are compared to measured three-phase generated x-ray transmission data in the literature and found to be reasonable. For calculation ease the data are fit to an equation previously shown to describe such curves quite well. These calculated transmission data are then used to create three-phase shielding tables for Pb and concrete, as well as other materials not available in Report No. 49 of the NCRP.

  14. Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma

    DEFF Research Database (Denmark)

    Johnsen, Kasper B.; Burkhart, Annette; Melander, Fredrik

    2017-01-01

    Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibi...... cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain....... investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does...... not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased...

  15. Carcinosarcoma of the Ureter with a Small Cell Component: Report of a Rare Pathologic Entity and Potential for Diagnostic Error on Biopsy

    Directory of Open Access Journals (Sweden)

    Kent Newsom

    2014-01-01

    Full Text Available Carcinosarcomas of the ureter are rare biphasic neoplasms, composed of both malignant epithelial (carcinomatous and malignant mesenchymal (sarcomatous components. Carcinosarcomas of the urinary tract are exceedingly rare. We report a unique case of a carcinosarcoma of the ureter with a chondrosarcoma and small cell tumor component arising in a 68-year-old male who presented with microscopic hematuria. CT intravenous pyelogram revealed right-sided hydroureter and hydronephrosis with thickening and narrowing of the right ureter. The patient underwent robot-assisted ureterectomy with bladder cuff excision and subsequent adjuvant chemotherapy. The patient is disease-free at 32 months after treatment. We provide a brief synoptic review of carcinosarcoma of the ureter and bladder with utilization of immunohistochemical (IHC stains and potential diagnostic pitfalls.

  16. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

    Directory of Open Access Journals (Sweden)

    Paulo C. J. L. Santos

    2012-02-01

    Full Text Available Hereditary hemochromatosis (HH is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV, hepcidin (HAMP, transferrin receptor 2 (TFR2 and ferroportin (SLC40A1 have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment.

  17. Mathematical modeling of mutant transferrin-CRM107 molecular conjugates for cancer therapy.

    Science.gov (United States)

    Yoon, Dennis J; Chen, Kevin Y; Lopes, André M; Pan, April A; Shiloach, Joseph; Mason, Anne B; Kamei, Daniel T

    2017-03-07

    The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites. In this work, we address this hurdle in cancer research by developing a mathematical model to predict the efficacy and selectivity of Tf conjugates that use an alternative toxin. For this purpose, we have chosen to study a mutant of DT, cross-reacting material 107 (CRM107). First, we developed a mathematical model of the Tf-DT trafficking pathway by extending our Tf/TfR model to include intracellular trafficking via DT and DT receptors. Using this mathematical model, we subsequently investigated the efficacy of several conjugates in cancer cells: DT and CRM107 conjugated to wild-type Tf, as well as to our engineered mutant Tf proteins (K206E/R632A Tf and K206E/R534A Tf). We also investigated the selectivity of mutant Tf-CRM107 against non-neoplastic cells. Through the use of our mathematical model, we predicted that (i) mutant Tf-CRM107 exhibits a greater cytotoxicity than wild-type Tf-CRM107 against cancerous cells, (ii) this improvement was more drastic with CRM107 conjugates than with DT conjugates, and (iii) mutant Tf-CRM107 conjugates were selective against non-neoplastic cells. These predictions were validated with in vitro cytotoxicity experiments, demonstrating that mutant Tf-CRM107 conjugates is indeed a more suitable therapeutic agent. Validation from in vitro experiments also confirmed that such whole

  18. Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

    Science.gov (United States)

    Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

    2017-12-01

    The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

  19. Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study.

    Science.gov (United States)

    Wu, Jing; Lu, Chanyi; Diao, Ni; Zhang, Shu; Wang, Sen; Wang, Feifei; Gao, Yan; Chen, Jiazhen; Shao, Lingyun; Lu, Jingning; Zhang, Xuelian; Weng, Xinhua; Wang, Honghai; Zhang, Wenhong; Huang, Yuxian

    2012-01-01

    To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive miRNAs. The potential targets for those miRNAs were also predicted by computational programs. Fourteen of 866 human miRNAs exhibited at least 1.8-fold difference in the ratio of expression level before and after stimulation with PPD between the ATB and HC groups. The qRT-PCR study validated the findings from microarray-based screening, in which miR-155 exhibited a fold change of 1.4 in the HC group and 3.7 in the ATB group upon PPD stimulation (p microRNAs exhibited no differences between the ATB and HC groups. miR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  20. MicroRNA-4639 Is a Regulator of DJ-1 Expression and a Potential Early Diagnostic Marker for Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Yimeng Chen

    2017-07-01

    Full Text Available Parkinson’s disease (PD is the second most common neurodegenerative disorder and has profound impacts on the daily lives of patients. However, there is a lack of effective biomarkers for early diagnosis, and the mechanisms of PD pathogenesis remain obscure. microRNAs (miRNAs are post-transcriptional gene regulators and can be easily detected in plasma, which suggests a promising role as diagnostic markers. Here, we aimed to explore a peripheral biomarker, which not only can be applied for early diagnosis of PD but also has the potential to be a therapeutic target. Through miRNA microarray screening and further validation in plasma from 169 sporadic PD patients, 170 healthy controls, and 60 essential tremor (ET patients, hsa-miR-4639-5p level was identified to be significantly up-regulated in PD patients. Also, it was able to discriminate between early PD patients (disease duration ≤2 years or Hoehn and Yahr stage 1–2.5 and healthy controls. Furthermore, hsa-miR-4639-5p was shown to negatively regulate DJ-1 (PARK7, a well-known PD-related gene, in the post-transcriptional level. Abnormal up-regulation of hsa-miR-4639-5p caused down-regulation of DJ-1 protein level, leading to severe oxidative stress and neuronal death. In conclusion, hsa-miR-4639-5p has the potential to be a peripheral diagnostic biomarker and therapeutic target for early PD.

  1. MiRNA-155 and miRNA-132 as potential diagnostic biomarkers for pulmonary tuberculosis: A preliminary study.

    Science.gov (United States)

    Zheng, Meng-Li; Zhou, Nai-Kang; Luo, Cheng-Hua

    2016-11-01

    In our study, we aimed to profile a panel microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to illuminate the molecular mechanisms in the development of PTB. Firstly, gene expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)-infected individuals and healthy subjects. Furthermore, in order to assess the performance of our methodology, random forest (RF) classification model was utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC) using 10-fold cross-validation method. Additionally, Monte Carlo Cross-Validation was repeated 50 times to explore the best miRNAs. In order to learn more about the differentially-expressed miRNAs, the target genes of differentially-expressed miRNAs were retrieved from TargetScan database and Ingenuity Pathways Analysis (IPA) was used to screen out biological pathways where target genes were involved. After normalization, a total of 478 miRNAs with higher than 0.25-fold quantile average across all samples were required. Based on the differential expression analysis, 38 differentially expressed miRNAs were identified when the significance was set as false discovery rate (FDR) < 0.01. Among the top 10 differentially expressed miRNAs, miRNA-155 obtained a highest AUC value 0.976, showing a good performance between PTB and control groups. Similarly, miRNA-449a, miRNA-212 and miRNA-132 revealed also a good performance with AUC values 0.947, 0.931 and 0.930, respectively. Moreover, miRNA-155, miRNA-449a, miRNA-29b-1* and miRNA-132 appeared in 50, 49, 49 and 48 bootstraps. Thus, miRNA-155 and miRNA-132 might be important in the progression of PTB and thereby, might present potential signatures for diagnosis of PTB. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Synthesis and In Vitro and In Vivo Evaluation of Iodine-131-Labeled Folates: Potential Molecular Diagnostic and Therapeutic Radiopharmaceuticals

    International Nuclear Information System (INIS)

    Al Jammaz, I.

    2009-01-01

    Molecular targeting imaging has a great potential to be able to image molecular changes that are currently defined as predisease states which facilitate earlier detection of cancer and consequently, the greatest chance of cure. Advancement of scintigraphic imaging and radiotherapy is highly determined by development of more specific radiotracers. The Membrane-associated-folic acid receptor is a glycosylphospstidylinositol protein that overexpressed in approximately 100% of serious ovarian adenocarcinomas and various epithelial cancers including cervical, colorectal and renal cancers. Meanwhile, this receptor is highly restricted in most normal tissues which make these tumors as an excellent candidates for molecular targeting imaging and therapy through the folate receptor system. As part of our on-going research effort to develop prosthetic precursors for radiohalogenation of bioactive molecules, we have previously reported the synthesis and biological characterization of [ 18 F]- fluorobenzene and pyridine carbohydrazide-folate conjugates ([ 18 F]-SFB and [ 18 F]-SFP-folates). We here report the synthesis and biological characterization of [ 131 I]-iodobenzenecarbohydrazide-folate conjugate ([ 131 I]-SIB-folate) as a potential therapeutic radiopharmaceutical. The synthetic approaches for preparation of [ 131 I]iodobenzene carbohydrazide-folates ([ 131 I]-SIB-folate) entailed sequence of reactions. Hydrazide-folate was reacted with N-succinimidyl-m-[131I]-iodobenzoate-carboxylate ([ 131 I]-SIB) to give [ 131 I]-SIB-folate conjugate. Radiochemical yield was greater than 80% and synthesis times were ranging between 40-45 min. Radiochemical purity was also greater than 97% without HPLC purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiohalogenation of folate in high radiochemical yield in short time. In vitro tests on KB cell line has shown that significant amount of the radioconjugate associated with cell

  3. Studies of metal binding by the iron transport protein transferrin using time differential perturbed angular correlation spectroscopy

    International Nuclear Information System (INIS)

    Then, G.M.

    1987-01-01

    The binding of the transition metal hafnium to transferrin was studied under various chemical conditions using time differential perturbed γγ angular correlation spectroscopy (TDPAC). Observing the electric quadrupole interaction of the 181 Hf probe nuclei size and symmetry of the electric field gradient induced by the ligands of the metal ions can be determined. The experimental data suggest how homogeneous the binding conditions are and to which extend relaxation phenomena are involved. Due to the excellent time resolution obtained with new BaF 2 detectors the quadrupole coupling parameters of 181 Hf-transferrin could be determined very accurately. Under nearly physiological conditions different binding configurations were quantitatively characterized by spectroscopic means and distinguished with high specificity. (orig./PW) [de

  4. Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study.

    Science.gov (United States)

    Sayanthooran, Saravanabavan; Magana-Arachchi, Dhammika N; Gunerathne, Lishanthe; Abeysekera, Tilak

    2017-01-19

    In Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). Identification of novel biomarkers that are customized to the specific causative factors would lead to early diagnosis and clearer prognosis of the diseases. This study aimed to find genetic biomarkers in blood to distinguish and identify CKDu from CKD as well as healthy populations from CKDu endemic and non-endemic areas of Sri Lanka. The expression patterns of a selected panel of 12 potential genetic biomarkers were analyzed in blood using RT-qPCR. Fold changes of gene expressions in early and late stages of CKD and CKDu patients, and an apparently healthy population of a CKDu endemic area, Girandurukotte (GH) were calculated relative to apparently healthy volunteers from a CKDu non-endemic area, Kandy (KH) of Sri Lanka, using the comparative CT method. Significant differences were observed between KH and early stage CKDu for both the insulin-like growth factor binding protein 1 (IGFBP1; p = 0.012) and kidney injury molecule-1 (KIM1; p = 0.003) genes, and KH and late stage CKD and CKDu for the glutathione-S-transferase mu 1 (GSTM1; p CKDu (p CKDu, whereas these genes in addition with FN1, IGFBP3 and KLK1 could be used to monitor progression of CKDu. The regulation of these genes has to be studied on larger populations to validate their efficiency for further clinical use.

  5. Expression of the Tpanxb1 gene from Taenia pisiformis and its potential diagnostic value by dot-ELISA.

    Science.gov (United States)

    Yang, Deying; Chen, Lin; Wu, Xuhang; Zhou, Xuan; Li, Mei; Chen, Zuqin; Nong, Xiang; Gu, Xiaobin; Peng, Xuerong; Yang, Guangyou

    2014-04-01

    Cysticercosis, caused by the larvae of Taenia pisiformis, is a common disease in rabbits that results in economic losses. To date, there has been limited information available on the early detection of infection by this parasite. This study describes a dot-ELISA method based on an autologous antigen annexin B1 (Tpanxb1). Its potential for serodiagnosis of rabbit cysticercosis was also evaluated. Western blot analysis revealed that the recombinant Tpanxb1 (rTpanxb1) protein could be specifically recognized by rabbit anti-sera. In serum trials, the antibodies could be detected by dot-ELISA using rTpanxb1 at 14 days post-infection. The positive response was present for up to 49 days post-infection. Based on the necropsy results of 169 rabbit samples, the relative sensitivity and specificity of the dot-ELISA were 94.55% and 92.86%, respectively. This study provides a foundation for studying the immunological function of annexin and its application to control Taenia cestodes.

  6. Is the neutrophil-to-lymphocyte ratio a potential diagnostic marker for peptic ulcer perforation? A retrospective cohort study.

    Science.gov (United States)

    Tanrikulu, Yusuf; Sen Tanrikulu, Ceren; Sabuncuoglu, Mehmet Zafer; Kokturk, Furuzan; Temi, Volkan; Bicakci, Ercan

    2016-03-01

    Peptic ulcer perforation (PUP) accounts for 5% of all abdominal emergencies and is recognized as a gastrointestinal emergency requiring rapid and efficient clinical evaluation and treatment. The mortality rate ranges from 10% to 40% among patients with perforation. In the present retrospective study, we examined the potential utility of the neutrophil-to-lymphocyte ratio (NLR) in early diagnosis of PUP; we asked whether this ratio allowed PUP and peptic ulcer disease to be distinguished. We enrolled the following patients: 58 with PUP, 62 with noncomplicated peptic ulcer diseases (NCPU), and 62 controls, between May 2010 and 2015. Patients who underwent surgical repair to treat PUP were included in the study group. Another group consisted of NCPU patients who had a noncomplicated peptic ulcer. The control group consisted of patients presenting with nonspecific abdominal pain to the emergency department. The mortality rate was 5.2% in the PUP group. The white blood cell count, C-reactive protein, and NLRs were higher in the PUP compared to the other groups (Ppeptic ulcer disease. Thus, the NLR should be calculated in addition to the clinical examination. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Comparative evaluation of the diagnostic potential of recombinant envelope proteins and native cell culture purified viral antigens of Chikungunya virus.

    Science.gov (United States)

    Khan, Mohsin; Dhanwani, Rekha; Kumar, Jyoti S; Rao, P V Lakshmana; Parida, Manmohan

    2014-07-01

    Despite the fact that Chikungunya resurgence is associated with epidemic of unprecedented magnitude, there are challenges in the field of its clinical diagnosis. However, serological tests in an ELISA format provide a rapid tool for the diagnosis of Chikungunya infection. Indeed, ELISAs based on recombinant proteins hold a great promise as these methods are cost effective and are free from the risk of handling biohazardous material. In this study, the performance of recombinant CHIKV antigens was compared in various ELISA formats for the diagnosis of Chikungunya. Two recombinant antigens derived from the envelope proteins of Chikungunya virus were prepared and evaluated by comparing their competence for detecting circulating antibodies in serum samples of patients infected with CHIKV using MAC-ELISA and indirect IgM-ELISA. The efficacy of the recombinant antigens was also compared with the native antigen. The indirect antibody capture IgM microplate ELISA revealed ≥90% concordance with the native antigen in detecting the CHIKV specific IgM antibodies whereas the recombinant antigen based MAC-ELISA showed 100% specificity. The recombinant antigens used in this study were effective and reliable targets for the diagnosis of CHIKV infection and also provide an alternative for native antigen use which is potentially biohazardous. © 2013 Wiley Periodicals, Inc.

  8. Fluorescence Imaging of Streptococcus pneumoniae with the Helix pomatia agglutinin (HPA As a Potential, Rapid Diagnostic Tool

    Directory of Open Access Journals (Sweden)

    Mirian Domenech

    2017-07-01

    Full Text Available Streptococcus pneumoniae is a common human pathogen and a major causal agent of life-threatening infections that can either be respiratory or non-respiratory. It is well known that the Helix pomatia (edible snail agglutinin (HPA lectin shows specificity for terminal αGalNAc residues present, among other locations, in the Forssman pentasaccharide (αGalNAc1→3βGalNAc1→3αGal1→4βGal1→4βGlc. Based on experiments involving choline-independent mutants and different growth conditions, we propose here that HPA recognizes the αGalNAc terminal residues of the cell wall teichoic and lipoteichoic acids of S. pneumoniae. In addition, experimental evidence showing that pneumococci can be specifically labeled with HPA when growing as planktonic cultures as well as in mixed biofilms of S. pneumoniae and Haemophilus influenzae has been obtained. It should be underlined that pneumococci were HPA-labeled despite of the presence of a capsule. Although some non-pneumococcal species also bind the agglutinin, HPA-binding combined with fluorescence microscopy constitutes a suitable tool for identifying S. pneumoniae and, if used in conjunction with Gram staining and/or other suitable technique like antigen detection, it may potentially facilitate a fast and accurate diagnosis of pneumococcal infections.

  9. Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications.

    Science.gov (United States)

    Reid, Michelle D; Saka, Burcu; Balci, Serdar; Goldblum, Andrew S; Adsay, N Volkan

    2014-02-01

    To summarize the most clinically and biologically relevant advances in molecular/genetic characteristics of various pancreatic neoplasms, with morphologic correlation. Whole-exome sequencing of numerous benign and malignant pancreatic tumors, along with the plethora of highly sensitive molecular studies now available for analyzing these tumors, provide mounting evidence to support the long-held belief that cancer is essentially a genetic disease. These genetic discoveries have not only helped to confirm the age-old, morphology-based classifications of pancreatic neoplasia but have shed new light on their mechanisms. Many of these molecular discoveries are currently being used in preoperative diagnosis. Mutations in KRAS, P16/CDKN2A, TP53, and SMAD4/DPC4 are commonly seen in ductal neoplasia but not in nonductal tumors; ductal adenocarcinomas with SMAD4/DPC4 loss are associated with widespread metastasis and poor prognosis. GNAS and RNF43 mutations have been discovered in most intraductal pancreatic mucinous neoplasms, providing critical molecular fingerprints for their diagnosis. Mutation in DAXX/ATRX is only seen in pancreatic neuroendocrine tumors, making it a useful potential marker in distinguishing these tumors from mimics. When combined with morphologic observations, molecular studies will increase our understanding of the pathogenesis and morphomolecular signatures associated with specific neoplasms and provide new horizons for precision medicine and targeted therapies.

  10. Fluorescence imaging of bombesin and transferrin receptor expression is comparable to 18F-FDG PET in early detection of sorafenib-induced changes in tumor metabolism.

    Directory of Open Access Journals (Sweden)

    Jen-Chieh Tseng

    noticeable changes in tumor size. For comparison, two FLI probes, BombesinRSense™ 680 (BRS-680 and Transferrin-Vivo™ 750 (TfV-750, were assessed for their potential in metabolic imaging. Metabolically active cancer cells are known to have elevated bombesin and transferrin receptor levels on the surface. In excellent agreement with PET imaging, the BRS-680 imaging showed 40% and 79% inhibition on days 2 and 3, respectively, and the TfV-750 imaging showed 65% inhibition on day 3. In both cases, no significant reduction in tumor volume or BLI signal was observed during the first 3 days of treatment. These results suggest that metabolic FLI has potential preclinical application as an additional method for detecting drug-induced metabolic changes in tumors.

  11. Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens.

    Science.gov (United States)

    Rodrigues, Anderson Messias; Fernandes, Geisa Ferreira; Araujo, Leticia Mendes; Della Terra, Paula Portella; dos Santos, Priscila Oliveira; Pereira, Sandro Antonio; Schubach, Tânia Maria Pacheco; Burger, Eva; Lopes-Bezerra, Leila Maria; de Camargo, Zoilo Pires

    2015-01-01

    Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans. We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20). Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94-1; Psporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis. A convergent IgG-response in various hosts (mice, cats, and humans) has important implications for our understanding of the coevolution of Sporothrix and its warm-blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the serological diagnosis of sporotrichosis and as target for the development of an effective multi-species vaccine against sporotrichosis in animals and humans.

  12. Studies on the mechanism of pyrophosphate-mediated uptake of iron from transferrin by isolated rat-liver mitochondria

    International Nuclear Information System (INIS)

    Konopka, K.; Romslo, I.; Bergen Univ.

    1981-01-01

    1. Respiring rat liver mitochondria accumulate iron released from transferrin by pyrophosphate. The amount of iron accumulated is 1-1.5 nmol mg protein -1 h -1 , or approximately 60% of the amount of iron mobilized from transferrin. 2. The uptake declines if respiration is inhibited, substrate is depleted, or the experiments are run under anaerobic conditions. Substrate, depletion and respiratory inhibitors are less inhibitory under anaerobic conditions. 3. More than 80% of the amount of iron accumulated by aerobic, actively respiring mitochondria can be chelated by bathophenanthroline sulphonate, and with deuteroporphyrin included, up to 30% of the amount of iron accumulated is recovered as deuteroheme. Iron accumulated by respiration-inhibited mitochondria under aerobic conditions is not available for heme synthesis. 4. With time the uptake of iron increases eightfold relative to the uptake of pyrophosphate. 5. The results are compatible with a model in which ferric iron is mobilized from transferrin by pyrophosphate, ferric iron pyrophosphate is bound to the mitochondria, iron is reduced, dissociates from pyrophosphate and is taken up by the mitochondria. Ferrous irons thus formed is available for heme synthesis. (orig.) [de

  13. Non-transferrin-bound iron (NTBI uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species.

    Directory of Open Access Journals (Sweden)

    Joao Arezes

    Full Text Available Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI. NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.

  14. Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens.

    Directory of Open Access Journals (Sweden)

    Anderson Messias Rodrigues

    understanding of the coevolution of Sporothrix and its warm-blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the serological diagnosis of sporotrichosis and as target for the development of an effective multi-species vaccine against sporotrichosis in animals and humans.

  15. Effects of epidermal growth factor, transferrin, and insulin on lipofection efficiency in human lung carcinoma cells.

    Science.gov (United States)

    Yanagihara, K; Cheng, H; Cheng, P W

    2000-01-01

    Poor transfection efficiency is the major drawback of lipofection. We showed previously that addition of transferrin (TF) to Lipofectin enhanced the expression of a reporter gene in HeLa cells by 120-fold and achieved close to 100% transfection efficiency. The purpose of this study was to determine whether TF and other ligands could improve the efficiency of lipofection in lung carcinoma cells. Confluent A549, Calu3, and H292 cells were transfected for 18 hours with a plasmid DNA (pCMVlacZ) using Lipofectin plus TF, insulin, or epidermal growth factor as the vector. The transfected cells were assessed for transfection efficiency by beta-galactosidase activity (light units/microg protein) and the percentage of blue cells following 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside staining. Lipofectin supplemented with epidermal growth factor yielded the largest enhancement of lipofection efficiency (lipofection efficiency in A549 and Calu3 cells but not in H292 cells, whereas TF showed significant lipofection efficiency-enhancing effect in Calu3 and H292 cells but not in A549 cells. The transfection efficiency correlated well with the amounts of DNA delivered to the nucleus as well as the amounts of the receptor. These results indicate that the gene delivery strategy employing ligand-facilitated lipofection can achieve high transfection efficiency in human lung carcinoma cells. In addition, enhancement of the expression of the receptor may be a possible strategy for increasing the efficiency of gene targeting.

  16. Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

    Science.gov (United States)

    Tan, Y; Chiow, KH; Huang, D; Wong, SH

    2010-01-01

    Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

  17. Transferrin coated nanoparticles: study of the bionano interface in human plasma.

    Directory of Open Access Journals (Sweden)

    Andrzej S Pitek

    Full Text Available It is now well established that the surface of nanoparticles (NPs in a biological environment is immediately modified by the adsorption of biomolecules with the formation of a protein corona and it is also accepted that the protein corona, rather than the original nanoparticle surface, defines a new biological identity. Consequently, a methodology to effectively study the interaction between nanomaterials and the biological corona encountered within an organism is a key objective in nanoscience for understanding the impact of the nanoparticle-protein interactions on the biological response in vitro and in vivo. Here, we outline an integrated methodology to address the different aspects governing the formation and the function of the protein corona of polystyrene nanoparticles coated with Transferrin by different strategies. Protein-NP complexes are studied both in situ (in human plasma, full corona FC and after washing (hard corona, HC in terms of structural properties, composition and second-order interactions with protein microarrays. Human protein microarrays are used to effectively study NP-corona/proteins interactions addressing the growing demand to advance investigations of the extrinsic function of corona complexes. Our data highlight the importance of this methodology as an analysis to be used in advance of the application of engineered NPs in biological environments.

  18. Reference values for serum ferritin and percentage of transferrin saturation in Korean children and adolescents.

    Science.gov (United States)

    Oh, Hea Lin; Lee, Jun Ah; Kim, Dong Ho; Lim, Jung Sub

    2018-03-01

    Ferritin reference values vary by age, gender, and ethnicity. We aimed to determine reference values of serum ferritin (SF) and the percentage of transferrin saturation (TSAT) for Korean children and adolescents. We analyzed data from 2,487 participants (1,311 males and 1,176 females) aged 10-20 years from the Korea National Health and Nutrition Examination Survey (2010-2012). We calculated age- and gender-stratified means and percentile values for SF and TSAT. We first plotted mean SF and TSAT by gender and according to age. In males, mean SF tended to be relatively constant among participants aged 10 to 14 years, with an upward trend thereafter. Mean SF trended downward among female participants until the age of 15 years and remained constant thereafter. Thus, significant gender differences in ferritin exist from the age of 14 years. High levels of SF were associated with obesity, and lower SF levels were associated with anemia and menarche status. We established reference values of SF and TSAT according to age and gender. The reference values for SF calculated in this study can be used to test the association between SF values and other defined diseases in Korean children and adolescents.

  19. Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier

    International Nuclear Information System (INIS)

    Friden, P.M.; Walus, L.R.; Musso, G.F.; Taylor, M.A.; Malfroy, B.; Starzyk, R.M.

    1991-01-01

    Delivery of nonlipophilic drugs to the brain is hindered by the tightly apposed capillary endothelial cells that make up the blood-brain barrier. The authors have examined the ability of a monoclonal antibody (OX-26), which recognizes the rat transferrin receptor, to function as a carrier for the delivery of drugs across the blood-brain barrier. This antibody, which was previously shown to bind preferentially to capillary endothelial cells in the brain after intravenous administration, labels the entire cerebrovascular bed in a dose-dependent manner. The initially uniform labeling of brain capillaries becomes extremely punctate ∼ 4 hr after injection, suggesting a time-dependent sequestering of the antibody. Capillary-depletion experiments, in which the brain is separated into capillary and parenchymal fractions, show a time-dependent migration of radiolabeled antibody from the capillaries into the brain parenchyma, which is consistent with the transcytosis of compounds across the blood-brain barrier. Antibody-methotrexate conjugates were tested in vivo to assess the carrier ability of this antibody. Immunohistochemical staining for either component of an OX-26-methotrexate conjugate revealed patterns of cerebrovascular labeling identical to those observed with the unaltered antibody. Accumulation of radiolabeled methotrexate in the brain parenchyma is greatly enhanced when the drug is conjugated to OX-26

  20. Soluble Form of Canine Transferrin Receptor Inhibits Canine Parvovirus Infection In Vitro and In Vivo

    Science.gov (United States)

    Wen, Jiexia; Pan, Sumin; Liang, Shuang; Zhong, Zhenyu; He, Ying; Lin, Hongyu; Li, Wenyan; Wang, Liyue; Li, Xiujin; Zhong, Fei

    2013-01-01

    Canine parvovirus (CPV) disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR) was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR)) possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo. PMID:24089666

  1. Soluble Form of Canine Transferrin Receptor Inhibits Canine Parvovirus Infection In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Jiexia Wen

    2013-01-01

    Full Text Available Canine parvovirus (CPV disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo.

  2. Transgenic HFE-dependent induction of hepcidin in mice does not require transferrin receptor-2.

    Science.gov (United States)

    Schmidt, Paul J; Fleming, Mark D

    2012-06-01

    Hereditary hemochomatosis (HH) is caused by mutations in several genes, including HFE and transferrin receptor-2 (TFR2). Loss of either protein decreases expression of the iron regulatory hormone hepcidin by the liver, leading to inappropriately high iron uptake from the diet, and resulting in systemic iron overload. In tissue culture, overexpressed HFE and TFR2 physically interact. Hepatocellular overexpression of Hfe in vivo increases hepcidin expression, despite an associated decrease in Tfr2. On this basis, we hypothesized that Tfr2 would not be required for Hfe-dependent up-regulation of hepcidin. We show that hepatocellular overexpression of Hfe in Tfr2(Y245X/Y245X) mice leads to hepcidin induction eventuating in iron deficiency and a hypochromic, microcytic anemia. Furthermore, coimmunoprecipitation studies using liver lysates did not provide evidence for physical interaction between Hfe and Tfr2 in vivo. In conclusion, we demonstrate that Tfr2 is not essential for Hfe-mediated induction of hepcidin expression, supporting the possibility that TFR2 may regulate iron metabolism in an HFE-independent manner. Copyright © 2012 Wiley Periodicals, Inc.

  3. Reference limits and behaviour of serum transferrin receptor in children 6-10 years of age.

    Science.gov (United States)

    Danise, P; Maconi, M; Morelli, G; Di Palma, A; Rescigno, G; Esposito, C; Avino, D; Talento, B

    2008-08-01

    Serum transferrin receptor (sTfR) originates mostly from erythroblasts and lesser from reticulocytes. The usefulness of sTfR has been implicated in several clinical situations, mainly as a marker of accelerated erythropoiesis or iron deficiency. The assessment of sTfR may be useful in the period of rapid growth during infancy, childhood and adolescence. We evaluated sTfR and the other quantitative and qualitative parameters of the erythropoiesis (Hb, MCV, CHr, Ret-He) and of the iron storage (serum ferritin, sTfR/ferritin index) in a total of 916 children aged 6-10 years. Children were divided into three groups: (A) healthy children, (B) with storage iron deficiency (serum ferritin 3.3). We determined reference intervals by sex and by age in healthy children. sTfR showed a slight but statistically significant age related increase but did not show significant sex differences. We compared sTfR and the other parameters investigated in the three groups of children. sTfR is not a decisive parameter that can be utilized alone in discriminating the border-line situations between normal and pathologic ones but can help in completing the panel of tests in iron deficiency and in thalassaemia Beta trait carriers.

  4. The distribution of iron between the metal-binding sites of transferrin human serum.

    Science.gov (United States)

    Williams, J; Moreton, K

    1980-02-01

    The Makey & Seal [(1976) Biochim. Biophys. Acta 453, 250--256] method of polyacrylamide-gel electrophoresis in buffer containing 6 M-urea was used to determine the distribution of iron between the N-terminal and C-terminal iron-binding sites of transferrin in human serum. In fresh serum the two sites are unequally occupied; there is preferential occupation of the N-terminal site. On incubation of the serum at 37 degrees C the preference of iron for the N-terminal site becomes more marked. On storage of serum at -15 degrees C the iron distribution changes so that there is a marked preference for the C-terminal site. Dialysis of serum against buffer at pH 7.4 also causes iron to be bound much more strongly by the C-terminal than by the N-terminal site. The original preference for the N-terminal site can be resroted to the dialysed serum by addition of the diffusible fraction.

  5. Synthesis and in vitro/in vivo evaluation of novel mono- and trivalent technetium-99m labeled ghrelin peptide complexes as potential diagnostic radiopharmaceuticals

    International Nuclear Information System (INIS)

    Koźmiński, Przemysław; Gniazdowska, Ewa

    2015-01-01

    Introduction: Ghrelin is an endogenous hormone present in blood. It is released from the oxyntic cells (X/A-like cells) of the stomach and fundus and can exist in two forms: as an acylated and des-acylated ghrelin. Ghrelin is an endogenous ligand of the growth hormone receptor (growth hormone secretagogue receptor, GHS-R). Overexpression of GHS-R1a receptor was identified in cells of different types of tumors (e.g. pituitary adenoma, neuroendocrine tumors of the thyroid, lung, breast, gonads, prostate, stomach, colorectal, endocrine and non-endocrine pancreatic tumors). This fact suggests that gamma radionuclide labeled ghrelin peptide may be considered as a potential diagnostic radiopharmaceutical. Methods: Ghrelin peptide labeled with mono- and trivalent technetium-99m complexes, 99m Tc-Lys-GHR, has been prepared on the n.c.a. scale. The physicochemical (stability, charge, shape, lipophilicity) and biological (receptor affinity, biodistribution) properties of the conjugates have been studied relevant to use the conjugates as receptor-based diagnostic radiopharmaceuticals. Results: The obtained conjugates [ 99m Tc(CO) 3 L N,O (CN-Lys-GHR)] + , 99m Tc(CO) 3 L S,O (CN-Lys-GHR) and 99m Tc(NS 3 )(CN-Lys-GHR) show different shape, charge, lipophilicity and two of them, 99m Tc(CO) 3 L S,O (CN-Lys-GHR) and 99m Tc(NS 3 )(CN-Lys-GHR), high stability in neutral aqueous solutions, even in the presence of excess concentration of histidine/cysteine competitive standard ligands or human serum. The in vitro binding affinity of 99m Tc-Lys-GHR conjugates with respect to growth hormone secretagogue receptor (GHS-R1a) present on DU-145 cells was in the range of IC 50 from 45 to 54 nM. The conjugate 99m Tc(CO) 3 L S,O (CN-Lys-GHR) exhibited excretion route by the liver and kidney in comparable degree, while the more lipophilic conjugate 99m Tc(NS 3 )(CN-Lys-GHR)—mainly by the liver. Conclusions: Basing on the results concerning physicochemical and biochemical properties, the

  6. Changes in iron levels, total iron binding capacity, transferrin saturation in race horses, before and after of physical exercise

    Directory of Open Access Journals (Sweden)

    Gláucia Abramovitc

    2014-09-01

    Full Text Available ABSTRACT. Abramovitc G., Parra A.C. & Fernandes W.R. [Changes in iron levels, total iron binding capacity, transferrin saturation in race horses, before and after of physical exercise]. Variação de níveis séricos de ferro, da capacidade total de ligação do ferro e da saturação da transferrina em equinos de corrida, antes e após exercício físico. Revista Brasileira de Medicina Veterinária, 36(3:289-293, 2014. Departamento de Clínica Médica, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Rua Prof. Dr. Orlando Marques de Paiva 87, Cidade Universitária, Butantã, São Paulo, SP 05508-270, Brasil. Email: wilsonrf@usp.br The preparation of the horse for physical activities in competition is directly related to important factors such as nutrition, muscle adaptation and blood profile, related to the concentration of serum iron, total capacity total iron binding capacity (TIBC and saturation of transferrin. This study aimed to evaluate the influence of exercise in iron levels, the total iron and transferrin saturation in race horses. One hundred and eleven samples of blood serum were collected from Thoroughbred horses, from the Jockey Club of São Paulo, aged between 3 and 4 years old, male and female, clinically healthy, practitioners turf competition, in sand or grass. The samples were obtained before exercise (control time and 30 minutes after exercise (post exercise. These animals were submitted to gallop training, of high intensity and short duration for this research. As a result, it was observed that the serum concentration of iron (Fe showed a statistically significant lowering post-exercise, due to organic re-balance of iron, while TIBC (total iron binding capacity showed a clear and significant increase in their serum levels due to increased needs of iron during and after exercise. The percentage of transferrin saturation in serum was shown to be lower post-exercise, probably due to the recruitment of

  7. Insights into the Diagnostic Potential of Extracellular Vesicles and Their miRNA Signature from Liquid Biopsy as Early Biomarkers of Diabetic Micro/Macrovascular Complications.

    Science.gov (United States)

    La Marca, Valeria; Fierabracci, Alessandra

    2017-09-14

    Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins and miRNAs) that allow the identification of their cell or tissue origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. A large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve information on the onset of peculiar disease manifestations. In this review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

  8. Expression of sheep pathogen Babesia sp. Xinjiang rhoptry-associated protein 1 and evaluation of its diagnostic potential by enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Niu, Qingli; Liu, Zhijie; Yang, Jifei; Yu, Peifa; Pan, Yuping; Zhai, Bintao; Luo, Jianxun; Guan, Guiquan; Yin, Hong

    2016-12-01

    Ovine babesiosis is one of the most important tick-borne haemoparasitic diseases of small ruminants. The ovine parasite Babesia sp. Xinjiang is widespread in China. In this study, recombinant full-length XJrRAP-1aα2 (rhoptry-associated protein 1aα2) and C-terminal XJrRAP-1aα2 CT of Babesia sp. Xinjiang were expressed and used to evaluate their diagnostic potential for Babesia sp. Xinjiang infections by indirect enzyme-linked immunosorbent assay (ELISA). Purified XJrRAP-1aα2 was tested for reactivity with sera from animals experimentally infected with Babesia sp. Xinjiang and other haemoparasites using Western blotting and ELISA. The results showed no cross-reactivities between XJrRAP-1aα2 CT and sera from animals infected by other pathogens. High level of antibodies against RAP-1a usually lasted 10 weeks post-infection (wpi). A total of 3690 serum samples from small ruminants in 23 provinces located in 59 different regions of China were tested by ELISA. The results indicated that the average positive rate was 30·43%, and the infections were found in all of the investigated provinces. This is the first report on the expression and potential use of a recombinant XJrRAP-1aα2 CT antigen for the development of serological assays for the diagnosis of ovine babesiosis, caused by Babesia sp. Xinjiang.

  9. Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec

    Directory of Open Access Journals (Sweden)

    Yu-Sheng Chen

    2018-01-01

    Full Text Available Proinsulin-transferrin fusion protein (ProINS-Tf has been designed and successfully expressed from the mammalian HEK293 cells (HEK-ProINS-Tf. It was found that HEK-ProINS-Tf could be converted into an activated form in the liver. Furthermore, HEK-ProINS-Tf was demonstrated as an extra-long acting insulin analogue with liver-specific insulin action in streptozotocin (STZ-induced type 1 diabetic mice. However, due to the low production yield from transfected HEK293 cells, there are other interesting features, including the oral bioavailability, which have not been fully explored and characterized. To improve the protein production yield, an alternative protein expression system, ExpressTec using transgenic rice (Oryza sativa L., was used. The intact and active rice-derived ProINS-Tf (ExpressTec-ProINS-Tf was successfully expressed from the transgenic rice expression system. Our results suggested that, although the insulin-like bioactivity of ExpressTec-ProINS-Tf was slightly lower in vitro, its potency of in vivo blood glucose control was considerably stronger than that of HEK-ProINS-Tf. The oral delivery studies in type 1 diabetic mice demonstrated a prolonged control of blood glucose to near-normal levels after oral administration of ExpressTec-ProINS-Tf. Results in this report suggest that ExpressTec-ProINS-Tf is a promising insulin analog with advantages including low cost, prolonged and liver targeting effects, and most importantly, oral bioactivity.

  10. Anemia and Iron Deficiency in Children With Potential Celiac Disease.

    Science.gov (United States)

    Repo, Marleena; Lindfors, Katri; Mäki, Markku; Huhtala, Heini; Laurila, Kaija; Lähdeaho, Marja-Leena; Saavalainen, Päivi; Kaukinen, Katri; Kurppa, Kalle

    2017-01-01

    Active screening for celiac disease frequently detects seropositive children with normal villous morphology (potential celiac disease). It remains unclear whether these subjects should be treated. We here investigated the prevalence of anemia and iron deficiency in children with potential and mucosal atrophy celiac disease. The prospective study involved 19 children with potential disease, 67 with partial or subtotal villous atrophy (P/SVA), and 16 with total villous atrophy (TVA). Twenty-three healthy children comprised the control group. The groups were compared for various clinical, histological, and laboratory parameters and hepcidin. The prevalence of abnormal parameters was as follows (controls, potential celiac disease, P/SVA, and TVA, respectively): anemia 0%, 15%, 22%, and 63%; low iron 5%, 0%, 14%, and 50%; increased transferrin receptor 1 5%, 16%, 20%, and 47%; low ferritin 0%, 21%, 35%, and 87%; and low transferrin saturation 10%, 11%, 41%, and 71%. One subject had low folate and none had low vitamin B12. The median values for hemoglobin, total iron, ferritin, and transferrin saturation were significantly lower and transferrin receptor 1 values higher in TVA group compared with other groups. After a median of 7 months on a gluten-free diet hemoglobin, total iron, ferritin, and albumin in children with P/SVA exceeded the baseline values in the potential celiac disease group. The development of anemia and iron deficiency in celiac disease is a continuum and may already be present in children with normal villous morphology, advocating an early diagnosis and possible dietary treatment of these patients.

  11. Curcumin and 5-Fluorouracil-loaded, folate- and transferrin-decorated polymeric magnetic nanoformulation: a synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia

    Directory of Open Access Journals (Sweden)

    Balasubramanian S

    2014-01-01

    Full Text Available Sivakumar Balasubramanian,1 Aswathy Ravindran Girija,1 Yutaka Nagaoka,1 Seiki Iwai,1 Masashi Suzuki,1 Venugopal Kizhikkilot,2 Yasuhiko Yoshida,1 Toru Maekawa,1 Sakthikumar Dasappan Nair1 1Bio Nano Electronics Research Center, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Japan; 2Department of Respiratory Medicine, Sooriya Hospital, Chennai, India Abstract: The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU] and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes by initiating early and late apoptosis. Keywords: nanotechnology, curcumin, 5FU, folate, transferrin, PLGA nanoparticle, magnetic hyperthermia

  12. Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma.

    Science.gov (United States)

    Johnsen, Kasper Bendix; Burkhart, Annette; Melander, Fredrik; Kempen, Paul Joseph; Vejlebo, Jonas Bruun; Siupka, Piotr; Nielsen, Morten Schallburg; Andresen, Thomas Lars; Moos, Torben

    2017-09-04

    Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain.

  13. The transferrin receptor of Actinobacillus pleuropneumoniae: Quantitation of expression and structural characterization using a peptide-specific monoclonal antibody

    DEFF Research Database (Denmark)

    Bøg, Yang S.; Andresen, Lars Ole; Bastholm, L.

    2001-01-01

    transferrin. This complex was studied using a monoclonal antibody (Mab 1.48) raised against a synthetic peptide corresponding to a hydrophilic domain of Tbp2 common to several A. pp serotypes. The antibody reacted specifically with a 60-70 kDa Tbp2-antigen found in all serotypes of A. pp obtained from iron...... expressing Tbp2 and in wild type A. pp grown under iron restricted conditions. The subcellular location of Tbp2 in A. pp was studied by immunoelectron microscopy using the Mab 1.48. Interestingly, all antibody binding was found inside the A. pp cells, while Tbp2 expressed in recombinant E. coli was found...

  14. Determination of Non-Transferrin Bound Iron, Transferrin Bound Iron, Drug Bound Iron and Total Iron in Serum in a Rats after IV Administration of Sodium Ferric Gluconate Complex by Simple Ultrafiltration Inductively Coupled Plasma Mass Spectrometric Detection

    Directory of Open Access Journals (Sweden)

    Murali K. Matta

    2018-02-01

    Full Text Available A rapid, sensitive and specific ultrafiltration inductively-coupled plasma mass spectrometry method was developed and validated for the quantification of non-transferrin bound iron (NTBI, transferrin bound iron (TBI, drug bound iron (DI and total iron (TI in the same rat serum sample after intravenous (IV administration of iron gluconate nanoparticles in sucrose solution (Ferrlecit®. Ultrafiltration with a 30 kDa molecular cut-off filter was used for sample cleanup. Different elution solvents were used to separate each form of iron from sample serum. Isolated fractions were subjected to inductively-coupled mass spectrometric analysis after microwave digestion in 4% nitric acid. The reproducibility of the method was evaluated by precision and accuracy. The calibration curve demonstrated linearity from 5–500 ng/mL with a regression (r2 of more than 0.998. This method was effectively implemented to quantify rat pharmacokinetic study samples after intravenous administration of Ferrlecit®. The method was successfully applied to a pharmacokinetic (PK study of Ferrlecit in rats. The colloidal iron followed first order kinetics with half-life of 2.2 h and reached background or pre-dose levels after 12 h post-dosing. The drug shown a clearance of 0.31 mL/min/kg and volume of distribution of 0.05 L/kg. 19.4 ± 2.4 mL/h/kg.

  15. Diagnosis of protein-losing gastroenteropathy by 111In-transferrin scanning and fecal excretion test

    International Nuclear Information System (INIS)

    Urita, Yoshihisa

    1991-01-01

    A total of 12 patients with gastroenteropathy were studied for possible protein loss. The underlying diseases were intestinal lymphangiectasia, ulcerative colitis and Crohn's disease in 2 patients each; and Menetrier's disease, Cronkhite-Canada syndrome, postgastrectomy syndrome, severe atrophic gastritis, gastric cancer and gastroenteropathy of unknown origin in one patient each. The controls were four healthy volunteers and 9 patients with benign disease not accompanied by lesions in the digestive tract and protein loss, 111 In-transferrin (Tf) was prepared by incubating 2-3 mCi of 111 In-chloride with 15-20 ml of each patient's plasma in a sterilized vial at room temperature for 1 hour. After i.v. injection of 111 In-Tf, the patients were scanned at given intervals of time for 72 hours to localize protein loss. Seventy-two hour fecal 111 In-Tf excretion was also measured. 111 In-Tf was detected in the feces of all patients. The recovery rate in the patient group was 7.95±3.65%, being significantly higher than 0.48±0.26% in the control group. However, 111 In-Tf scanning showed the site of protein loss only in 6 patients. Negative scan in six other patients was thought to be associated with extensive inflammation and severe diarrhea. Five of the 12 patients were observed before and after treatment. A decrease in fecal 111 In-Tf excretion with clinical improvement was noted in the 5 patients after treatment. The site of protein loss could be demonstrated in 3 of the 5 patients before treatment. Its site in 1 of the 3 patients was the small intestine. However, accumulation of 111 In-Tf was found there in the 3 patients after treatment. The site of protein loss in one of three patients was the small intestine. 111 In-Tf scanning is particularly useful when the small intestine is involved, because surgery is contraindicated in this case. Fecal 111 In-Tf excretion test is mandatory when the site of protein loss cannot be imaged. (author)

  16. Metal retention in human transferrin: consequences of solvent composition in analytical sample preparation methods.

    Science.gov (United States)

    Quarles, C Derrick; Randunu, K Manoj; Brumaghim, Julia L; Marcus, R Kenneth

    2011-10-01

    The analysis of metal-binding proteins requires careful sample manipulation to ensure that the metal-protein complex remains in its native state and the metal retention is preserved during sample preparation or analysis. Chemical analysis for the metal content in proteins typically involves some type of liquid chromatography/electrophoresis separation step coupled with an atomic (i.e., inductively coupled plasma-optical emission spectroscopy or -mass spectrometry) or molecular (i.e., electrospray ionization-mass spectrometry) analysis step that requires altered-solvent introduction techniques. UV-VIS absorbance is employed here to monitor the iron content in human holo-transferrin (Tf) under various solvent conditions, changing polarity, pH, ionic strength, and the ionic and hydrophobic environment of the protein. Iron loading percentages (i.e. 100% loading equates to 2 Fe(3+):1 Tf) were quantitatively determined to evaluate the effect of solvent composition on the retention of Fe(3+) in Tf. Maximum retention of Fe(3+) was found in buffered (20 mM Tris) solutions (96 ± 1%). Exposure to organic solvents and deionized H(2)O caused release of ~23-36% of the Fe(3+) from the binding pocket(s) at physiological pH (7.4). Salt concentrations similar to separation conditions used for ion exchange had little to no effect on Fe(3+) retention in holo-Tf. Unsurprisingly, changes in ionic strength caused by additions of guanidine HCl (0-10 M) to holo-Tf resulted in unfolding of the protein and loss of Fe(3+) from Tf; however, denaturing and metal loss was found not to be an instantaneous process for additions of 1-5 M guanidinium to Tf. In contrast, complete denaturing and loss of Fe(3+) was instantaneous with ≥6 M additions of guanidinium, and denaturing and loss of iron from Tf occurred in parallel proportions. Changes to the hydrophobicity of Tf (via addition of 0-14 M urea) had less effect on denaturing and release of Fe(3+) from the Tf binding pocket compared to changes

  17. Expression of the TPα and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer: clinical significance and diagnostic potential.

    Science.gov (United States)

    Mulvaney, Eamon P; Shilling, Christine; Eivers, Sarah B; Perry, Antoinette S; Bjartell, Anders; Kay, Elaine W; Watson, R William; Kinsella, B Therese

    2016-11-08

    The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

  18. Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma

    DEFF Research Database (Denmark)

    Johnsen, Kasper B.; Burkhart, Annette; Melander, Fredrik

    2017-01-01

    Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing...... the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we...... investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does...

  19. Loss of circulating 67Ga-transferrin due to its accumulation in malignant tumors of the rat and its relation to the synthesis of hemoglobin

    International Nuclear Information System (INIS)

    Kratzer, J.

    1981-01-01

    Taking into account earlier findings of other study groups, the author draws the following conclusions: 1. The elimination of 67 Ga-labelled transferrin from the blood of tumor carrier rats is accelerated as compared to normal. The acceleration is the more marked the greater the tumor mass and the higher its proliferation speed are. 2. The eliminated 67 Ga transferrin is detectable in the tumor by scintiscanning, and its retention increases concurrently with the tumor proliferation rate. 3. These tumor-dependent losses of transferrin entail a perturbation of reticulocytal Fe utilization and cause anemia, which is again aggravated as the tumor mass and its malignant nature increase. 4. If the tumor can be eliminated by therapy, the anemia disappears completely. (orig./MG) [de

  20. Molecular Diagnostics

    OpenAIRE

    Choe, Hyonmin; Deirmengian, Carl A.; Hickok, Noreen J.; Morrison, Tiffany N.; Tuan, Rocky S.

    2015-01-01

    Orthopaedic infections are complex conditions that require immediate diagnosis and accurate identification of the causative organisms to facilitate appropriate management. Conventional methodologies for diagnosis of these infections sometimes lack accuracy or sufficient rapidity. Current molecular diagnostics are an emerging area of bench-to-bedside research in orthopaedic infections. Examples of promising molecular diagnostics include measurement of a specific biomarker in the synovial fluid...

  1. Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of Iron Metabolism in Children on a Vegetarian Diet.

    Science.gov (United States)

    Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Mazur, Joanna; Gajewska, Joanna; Rowicka, Grażyna; Strucińska, Małgorzata; Chełchowska, Magdalena

    2017-12-01

    The aim of this study was to assess the effect of vegetarian diet on iron metabolism parameters paying special attention to serum hepcidin and soluble transferrin receptor (sTfR) concentrations in 43 prepubertal children (age range 4.5-9.0 years) on vegetarian and in 46 children on omnivorous diets. There were no significant differences according to age, weight, height, and body mass index (BMI) between vegetarian and omnivorous children. Vegetarians had similar intake of iron and vitamin B 12 and a significantly higher intake of vitamin C (p vegetarians. Hematologic parameters and serum iron concentrations were within the reference range in both groups of children. Serum transferrin levels were similar in all subjects; however, ferritin concentrations were significantly (p vegetarians than in omnivores. In children on a vegetarian diet, median hepcidin levels were lower (p vegetarians. We did not find significant associations with concentration of sTfR and selected biochemical, anthropometric, and dietary parameters in any of the studied groups of children. As hematologic parameters and iron concentrations in vegetarians and omnivores were comparable and ferritin level was lower in vegetarians, we suggest that inclusion of novel markers, in particular sTfR (not cofounded by inflammation) and hepcidin, can better detect subclinical iron deficiency in children following vegetarian diets.

  2. Transferrin-loaded nido-carborane liposomes. Synthesis and intracellular targeting to solid tumors for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Nakamura, Hiroyuki; Miyajima, Yusuke; Kuwata, Yasuhiro; Maruyama, Kazuo; Masunaga, Shinichiro; Ono, Koji

    2006-01-01

    The boron ion cluster lipids, as a double-tailed boron lipid synthesized from heptadecanol, formed stable liposomes at 25% molar ratio toward DSPC with cholesterol. Transferrin was able to be introduced on the surface of boron liposomes (Tf-PEG-CL liposomes) by the coupling of transferrin to the PEG-CO 2 H moieties of PEG-CL liposomes. The biodistribution of Tf-PEG-CL liposomes showed that Tf-PEG-CL liposomes accumulated in tumor tissues and stayed there for a sufficiently long time to increase tumor:blood concentration ratio. A 10 B concentration of 22 ppm in tumor tissues was achieved by the injection of Tf-PEG-CL liposome at 7.2 mg/kg body weight 10 B in tumor-bearing mice. After neutron irradiation, the average survival rate of mice not treated with Tf-PEG-CL liposomes was 21 days, whereas that of the treated mice was 31 days. Longer survival rates were observed in the mice treated with Tf-PEG-CL liposomes; one of them even survived for 52 days after BNCT. (author)

  3. α-Taxilin interacts with sorting nexin 4 and participates in the recycling pathway of transferrin receptor.

    Directory of Open Access Journals (Sweden)

    Hiroshi Sakane

    Full Text Available Membrane traffic plays a crucial role in delivering proteins and lipids to their intracellular destinations. We previously identified α-taxilin as a binding partner of the syntaxin family, which is involved in intracellular vesicle traffic. α-Taxilin is overexpressed in tumor tissues and interacts with polymerized tubulin, but the precise function of α-taxilin remains unclear. Receptor proteins on the plasma membrane are internalized, delivered to early endosomes and then either sorted to the lysosome for degradation or recycled back to the plasma membrane. In this study, we found that knockdown of α-taxilin induced the lysosomal degradation of transferrin receptor (TfnR, a well-known receptor which is generally recycled back to the plasma membrane after internalization, and impeded the recycling of transferrin. α-Taxilin was immunoprecipitated with sorting nexin 4 (SNX4, which is involved in the recycling of TfnR. Furthermore, knockdown of α-taxilin decreased the number and length of SNX4-positive tubular structures. We report for the first time that α-taxilin interacts with SNX4 and plays a role in the recycling pathway of TfnR.

  4. Comparison of diagnostic performance between single- and multiphasic contrast-enhanced abdominopelvic computed tomography in patients admitted to the emergency department with abdominal pain: potential radiation dose reduction.

    Science.gov (United States)

    Hwang, Shin Hye; You, Je Sung; Song, Mi Kyong; Choi, Jin-Young; Kim, Myeong-Jin; Chung, Yong Eun

    2015-04-01

    To evaluate feasibility of radiation dose reduction by optimal phase selection of computed tomography (CT) in patients who visited the emergency department (ED) for abdominal pain. We included 253 patients who visited the ED for abdominal pain. They underwent multiphasic CT including precontrast, late arterial phase (LAP), and hepatic venous phase (HVP). Three image sets (HVP, precontrast + HVP, and precontrast + LAP + HVP) were reviewed. Two reviewers determined the most appropriate diagnosis with five-point confidence scale. Diagnostic performances were compared among image sets by weighted-least-squares method or DeLong's method. Linear mixed model was used to assess changes of diagnostic confidence and radiation dose. There was no difference in diagnostic performance among three image sets, although diagnostic confidence level was significantly improved after review of triphasic images compared with both HVP images only or HVP with precontrast images (confidence scale, 4.64 ± 0.05, 4.66 ± 0.05, and 4.76 ± 0.04 in the order of the sets; overall P = 0.0008). Similar trends were observed in the subgroup analysis for diagnosis of pelvic inflammatory disease and cholecystitis. There is no difference between HVP-CT alone and multiphasic CT for the diagnosis of causes of abdominal pain in patients admitted to the ED without prior chronic disease or neoplasia. • There was no difference in diagnostic performance of HVP CT and multiphasic CT. • The diagnostic confidence level was improved after review of the LAP images. • HVP CT can achieve diagnostic performance similar to that of multiphasic CT, while minimizing radiation.

  5. Structural and functional consequences of binding site mutations in transferrin: crystal structures of the Asp63Glu and Arg124Ala mutants of the N-lobe of human transferrin.

    Science.gov (United States)

    Baker, Heather M; He, Qing-Yu; Briggs, Sara K; Mason, Anne B; Baker, Edward N

    2003-06-17

    Human transferrin is a serum protein whose function is to bind Fe(3+) with very high affinity and transport it to cells, for delivery by receptor-mediated endocytosis. Structurally, the transferrin molecule is folded into two globular lobes, representing its N-terminal and C-terminal halves, with each lobe possessing a high-affinity iron binding site, in a cleft between two domains. Central to function is a highly conserved set of iron ligands, including an aspartate residue (Asp63 in the N-lobe) that also hydrogen bonds between the two domains and an arginine residue (Arg124 in the N-lobe) that binds an iron-bound carbonate ion. To further probe the roles of these residues, we have determined the crystal structures of the D63E and R124A mutants of the N-terminal half-molecule of human transferrin. The structure of the D63E mutant, determined at 1.9 A resolution (R = 0.245, R(free) = 0.261), showed that the carboxyl group still binds to iron despite the larger size of the Glu side chain, with some slight rearrangement of the first turn of alpha-helix residues 63-72, to which it is attached. The structure of the R124A mutant, determined at 2.4 A resolution (R = 0.219, R(free) = 0.288), shows that the loss of the arginine side chain results in a 0.3 A displacement of the carbonate ion, and an accompanying movement of the iron atom. In both mutants, the iron coordination is changed slightly, the principal change being in each case a lengthening of the Fe-N(His249) bond. Both mutants also release iron more readily than the wild type, kinetically and in terms of acid lability of iron binding. We attribute this to more facile protonation of the synergistically bound carbonate ion, in the case of R124A, and to strain resulting from the accommodation of the larger Glu side chain, in the case of D63E. In both cases, the weakened Fe-N(His) bond may also contribute, consistent with protonation of the His ligand being an early intermediate step in iron release, following the

  6. Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis Treatment Response.

    Science.gov (United States)

    Jacobs, Ruschca; Maasdorp, Elizna; Malherbe, Stephanus; Loxton, Andre G; Stanley, Kim; van der Spuy, Gian; Walzl, Gerhard; Chegou, Novel N

    2016-01-01

    There is an urgent need for new tools for the early diagnosis of TB disease and monitoring of the response to treatment, especially in resource-constrained settings. We investigated the usefulness of host markers detected in saliva as candidate biomarkers for the immunological diagnosis of TB disease and monitoring of treatment response. We prospectively collected saliva samples from 51 individuals that presented with signs and symptoms suggestive of TB disease at a health centre in Cape Town, South Africa, prior to the establishment of a clinical diagnosis. Patients were later classified as having TB disease or other respiratory disease (ORD), using a combination of clinical, radiological and laboratory findings. We evaluated the concentrations of 69 host markers in saliva samples using a multiplex cytokine platform, and assessed the diagnostic potentials of these markers by receiver operator characteristics (ROC) curve analysis, and general discriminant analysis. Out of the 51 study participants, 18 (35.4%) were diagnosed with TB disease and 12 (23.5%) were HIV infected. Only two of the 69 host markers that were evaluated (IL-16 and IL-23) diagnosed TB disease individually with area under the ROC curve ≥0.70. A five-marker biosignature comprising of IL-1β, IL-23, ECM-1, HCC1 and fibrinogen diagnosed TB disease with a sensitivity of 88.9% (95% CI,76.7-99.9%) and specificity of 89.7% (95% CI, 60.4-96.6%) after leave-one-out cross validation, regardless of HIV infection status. Eight-marker biosignatures performed with a sensitivity of 100% (95% CI, 83.2-100%) and specificity of 95% (95% CI, 68.1-99.9%) in the absence of HIV infection. Furthermore, the concentrations of 11 of the markers changed during treatment, indicating that they may be useful in monitoring of TB treatment response. We have identified novel salivary biosignatures which may be useful in the diagnosis of TB disease and monitoring of the response to TB treatment. Our findings require further

  7. Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential diagnostic markers and risk predictors of venous thrombosis and obstetric complications in antiphospholipid syndrome.

    Science.gov (United States)

    Shi, Hui; Zheng, Hui; Yin, Yu-Feng; Hu, Qiong-Yi; Teng, Jia-Lin; Sun, Yue; Liu, Hong-Lei; Cheng, Xiao-Bing; Ye, Jun-Na; Su, Yu-Tong; Wu, Xin-Yao; Zhou, Jin-Feng; Norman, Gary L; Gong, Hui-Yun; Shi, Xin-Ming; Peng, Yi-Bing; Wang, Xue-Feng; Yang, Cheng-De

    2018-03-28

    The aim of the study was to determine the prevalence and clinical associations of antiphosphatidylserine/prothrombin antibodies (aPS/PT) with thrombosis and pregnancy loss in Chinese patients with antiphospholipid syndrome (APS) and seronegative APS (SNAPS). One hundred and eighty six Chinese patients with APS (67 primary, 119 secondary), 48 with SNAPS, 176 disease controls (79 systemic lupus erythematosus [SLE], 29 Sjogren's syndrome [SS], 30 ankylosing spondylitis [AS], 38 rheumatoid arthritis [RA]) and 90 healthy donors were examined. IgG and IgM aPS/PT, IgG/IgM/IgA anticardiolipin (aCL) and IgG/IgM/IgA anti-β2-glycoprotein I (anti-β2GPI) antibodies were tested by ELISA. One hundred and sixty (86.0%) of APS patients were positive for at least one aPS/PT isotype. One hundred and thirty five (72.6%) were positive for IgG aPS/PT, 124/186 (66.7%) positive for IgM aPS/PT and 99 (53.2%) positive for both. Approximately half of the SNAPS patients were positive for IgG and/or IgM aPS/PT. Highly significant associations between IgG aPS/PT and venous thrombotic events (odds ratio [OR]=6.72) and IgG/IgM aPS/PT and pregnancy loss (OR=9.44) were found. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations and those with fetal loss (p=0.014). The association between IgG/IgM aPS/PT and lupus anticoagulant (LAC) was highly significant (pAPS was 101.6. Notably, 91.95% (80/87) of LAC-positive specimens were positive for IgG and/or IgM aPS/PT, suggesting aPS/PT is an effective option when LAC testing is not available. Anti-PS/PT antibody assays demonstrated high diagnostic performance for Chinese patients with APS, detected some APS patients negative for criteria markers and may serve as potential risk predictors for venous thrombosis and obstetric complications.

  8. Transferrin-mediated PEGylated nanoparticles for delivery of DNA/PLL

    International Nuclear Information System (INIS)

    Gu Wangwen; Xu Zhenghong; Gao Yu; Chen Lingli; Li Yaping

    2006-01-01

    The purpose of this work was to determine the stability of pDNA/poly(L-lysine) complex (DNA/PLL) during microencapsulation, prepare transferrin (TF) conjugated PEGylated nanoparticles (TF-PEG-NP) loading DNA/PLL, and assess its physicochemical characteristics and in vitro transfection efficiency. The DNA/PLL was prepared by mixing plasmid DNA (pDNA) in deionized water with various amounts of PLL. PEGylated nanoparticles (PEG-NP) loading DNA/PLL were prepared by a water-oil-water double emulsion solvent evaporation technique. TF-PEG-NP was prepared by coupling TF with PEG-NP. The physicochemical characteristics of TF-PEG-NP and in vitro transfection efficiency on K562 cells were measured. The results showed that free pDNA reserved its double supercoiled form (dsDNA) for only on average 25.7% after sonification, but over 70% of dsDNA was reserved after pDNA was contracted with PLL. The particle size range of TF-PEG-NP loading DNA/PLL was 150-450 nm with entrapment efficiency over 70%. TF-PEG-NP exhibited the low burst effect (<10%) within 1 day. After the first phase, DNA/PLL displayed a sustained release. The amount of cumulated DNA/PLL release from TF-PEG-NP with 2% polymer over 7 days was 85.4% for DNA/PLL (1:0.3 mass ratio), 59.8% and 43.1% for DNA/PLL (1:0.6) and DNA/PLL (1:1.0), respectively. To TF-PEG-NP loading DNA/PLL without chloroquine, the percentage of EGFP expressing cells was 28.9% for complexes consisting of DNA/PLL (1:0.3), 38.5% and 39.7% for DNA/PLL (1:0.6) and DNA/PLL (1:1.0), respectively. In TF-PEG-NP loading DNA/PLL with chloroquine, more cells were transfected, the percentage of positive cells was 37.6% (DNA/PLL, 1:0.3), 47.1% (DNA/PLL, 1:0.6) and 45.8% (DNA/PLL, 1:1.0), which meant that the transfection efficiency of pDNA was increased by over 50 times when PLL and TF-PEG-NP were jointly used as a plasmid DNA carrier, in particular, the maximal percentage of positive cells (47.1%) from TF-PEG-NP loading DNA/PLL (1:0.6) was about 70 times the

  9. Companion diagnostics

    DEFF Research Database (Denmark)

    Jørgensen, Jan Trøst; Hersom, Maria

    2016-01-01

    of disease mechanisms, things are slowly changing. Within the last few years, we have seen an increasing number of predictive biomarker assays being developed to guide the use of targeted cancer drugs. This type of assay is called companion diagnostics and is developed in parallel to the drug using the drug-diagnostic...... co-development model. The development of companion diagnostics is a relatively new discipline and in this review, different aspects will be discussed including clinical and regulatory issues. Furthermore, examples of drugs, such as the ALK and PD-1/PD-L1 inhibitors, that have been approved recently....... Despite having discussed personalized medicine for more than a decade, we still see that most drug prescriptions for severe chronic diseases are largely based on 'trial and error' and not on solid biomarker data. However, with the advance of molecular diagnostics and a subsequent increased understanding...

  10. In vitro isotopic determination of diffusion volumes by transferrin labelled with indium 111. study of the correlation with SARI 125; Determination isotopique in vitro de volumes de diffusion par la transferrine marquee a l'indium 111. Etude de la correlation avec la SARI 125

    Energy Technology Data Exchange (ETDEWEB)

    Porot, C.L. [CHU Jean-Minjoz, Service de medecine nucleaire, 25 - Besancon (France); Angoue, O.R. [CHU Jean-Minjoz, laboratoire de biophysique et statistiques, 25 - Besancon (France); Berthetc, L.O. [CHU Jean-Minjoz, 25 - Besancon (France); Ungureanu, C.O.; Boulahdour, H.A.

    2010-07-01

    Serum albumin labeled with iodine 125 (S.A.R.I. 125) is the reference tracer used in measuring isotopic plasma volume. It has been causing a suspension of manufacturing leading to a supply disruption and resulting in the search for an alternative to measure plasma volume under consideration for measuring blood volume. Plasma transferrin labeled with indium-111 (Tf-{sup 111}In) is a potentially useful marker. To this end, we assessed the level of activity to be administered to determine a volume of distribution. The study of the correlation between the volume of distribution values obtained with S.A.R.I. 125 and Tf-{sup 111}In was then performed. Tf is an autologous protein which the labelling is easy and stable. Tf-{sup 111}In is a valid alternative to the S.A.R.I. 125 for measuring the plasma volume. The activity required for this examination shall not exceed 100 micro curies. (N.C.)

  11. Comparison of diagnostic performance between single- and multiphasic contrast-enhanced abdominopelvic computed tomography in patients admitted to the emergency department with abdominal pain: potential radiation dose reduction

    International Nuclear Information System (INIS)

    Hwang, Shin Hye; You, Je Sung; Choi, Jin-Young; Kim, Myeong-Jin; Chung, Yong Eun; Song, Mi Kyong

    2015-01-01

    To evaluate feasibility of radiation dose reduction by optimal phase selection of computed tomography (CT) in patients who visited the emergency department (ED) for abdominal pain. We included 253 patients who visited the ED for abdominal pain. They underwent multiphasic CT including precontrast, late arterial phase (LAP), and hepatic venous phase (HVP). Three image sets (HVP, precontrast + HVP, and precontrast + LAP + HVP) were reviewed. Two reviewers determined the most appropriate diagnosis with five-point confidence scale. Diagnostic performances were compared among image sets by weighted-least-squares method or DeLong's method. Linear mixed model was used to assess changes of diagnostic confidence and radiation dose. There was no difference in diagnostic performance among three image sets, although diagnostic confidence level was significantly improved after review of triphasic images compared with both HVP images only or HVP with precontrast images (confidence scale, 4.64 ± 0.05, 4.66 ± 0.05, and 4.76 ± 0.04 in the order of the sets; overall P = 0.0008). Similar trends were observed in the subgroup analysis for diagnosis of pelvic inflammatory disease and cholecystitis. There is no difference between HVP-CT alone and multiphasic CT for the diagnosis of causes of abdominal pain in patients admitted to the ED without prior chronic disease or neoplasia. (orig.)

  12. Comparison of diagnostic performance between single- and multiphasic contrast-enhanced abdominopelvic computed tomography in patients admitted to the emergency department with abdominal pain: potential radiation dose reduction

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Shin Hye; You, Je Sung; Choi, Jin-Young; Kim, Myeong-Jin; Chung, Yong Eun [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seodaemun-gu, Seoul (Korea, Republic of); Song, Mi Kyong [Yonsei University, Biostatistics Collaboration Unit, College of Medicine, Seoul (Korea, Republic of)

    2015-04-01

    To evaluate feasibility of radiation dose reduction by optimal phase selection of computed tomography (CT) in patients who visited the emergency department (ED) for abdominal pain. We included 253 patients who visited the ED for abdominal pain. They underwent multiphasic CT including precontrast, late arterial phase (LAP), and hepatic venous phase (HVP). Three image sets (HVP, precontrast + HVP, and precontrast + LAP + HVP) were reviewed. Two reviewers determined the most appropriate diagnosis with five-point confidence scale. Diagnostic performances were compared among image sets by weighted-least-squares method or DeLong's method. Linear mixed model was used to assess changes of diagnostic confidence and radiation dose. There was no difference in diagnostic performance among three image sets, although diagnostic confidence level was significantly improved after review of triphasic images compared with both HVP images only or HVP with precontrast images (confidence scale, 4.64 ± 0.05, 4.66 ± 0.05, and 4.76 ± 0.04 in the order of the sets; overall P = 0.0008). Similar trends were observed in the subgroup analysis for diagnosis of pelvic inflammatory disease and cholecystitis. There is no difference between HVP-CT alone and multiphasic CT for the diagnosis of causes of abdominal pain in patients admitted to the ED without prior chronic disease or neoplasia. (orig.)

  13. Cable Diagnostic Focused Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Hartlein, R.A.; Hampton, R.N.

    2010-12-30

    This report summarizes an extensive effort made to understand how to effectively use the various diagnostic technologies to establish the condition of medium voltage underground cable circuits. These circuits make up an extensive portion of the electric delivery infrastructure in the United States. Much of this infrastructure is old and experiencing unacceptable failure rates. By deploying efficient diagnostic testing programs, electric utilities can replace or repair circuits that are about to fail, providing an optimal approach to improving electric system reliability. This is an intrinsically complex topic. Underground cable systems are not homogeneous. Cable circuits often contain multiple branches with different cable designs and a range of insulation materials. In addition, each insulation material ages differently as a function of time, temperature and operating environment. To complicate matters further, there are a wide variety of diagnostic technologies available for assessing the condition of cable circuits with a diversity of claims about the effectiveness of each approach. As a result, the benefits of deploying cable diagnostic testing programs have been difficult to establish, leading many utilities to avoid the their use altogether. This project was designed to help address these issues. The information provided is the result of a collaborative effort between Georgia Tech NEETRAC staff, Georgia Tech academic faculty, electric utility industry participants, as well as cable system diagnostic testing service providers and test equipment providers. Report topics include: •How cable systems age and fail, •The various technologies available for detecting potential failure sites, •The advantages and disadvantages of different diagnostic technologies, •Different approaches for utilities to employ cable system diagnostics. The primary deliverables of this project are this report, a Cable Diagnostic Handbook (a subset of this report) and an online

  14. In Vitro and In Vivo Effect of HPMA Copolymer-bound Doxorubicin Targeted to Transferrin Receptor of B-cell Lymphoma 38C13

    Czech Academy of Sciences Publication Activity Database

    Kovář, Marek; Strohalm, Jiří; Ulbrich, Karel; Říhová, Blanka

    2002-01-01

    Roč. 10, č. 1 (2002), s. 23-30 ISSN 1061-186X Institutional research plan: CEZ:AV0Z5020903 Keywords : targeting * transferrin * hpma copolymer Subject RIV: EC - Immunology Impact factor: 2.045, year: 2002

  15. N-glycan structures of human transferrin produced by Lymantria dispar (gypsy moth)cells using the LdMNPV expression system

    Science.gov (United States)

    One Choi; Noboru Tomiya; Jung H. Kim; James M. Slavicek; Michael J. Betenbaugh; Yuan C. Lee

    2003-01-01

    N-glycan structures of recombinant human serum transferrin (hTf) expressed by Lymantria dispar (gypsy moth) 652Y cells were determined. The gene encoding hTf was incorporated into a Lymantria dispar nucleopolyhedrovirus (LdMNPV) under the control of the polyhedrin promoter. This virus was then...

  16. Plasma Diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Zaveryaev, V [Kurchatov Institute, Moscow (Russian Federation); others, and

    2012-09-15

    The success in achieving peaceful fusion power depends on the ability to control a high temperature plasma, which is an object with unique properties, possibly the most complicated object created by humans. Over years of fusion research a new branch of science has been created, namely plasma diagnostics, which involves knowledge of almost all fields of physics, from electromagnetism to nuclear physics, and up-to-date progress in engineering and technology (materials, electronics, mathematical methods of data treatment). Historically, work on controlled fusion started with pulsed systems and accordingly the methods of plasma parameter measurement were first developed for short lived and dense plasmas. Magnetically confined hot plasmas require the creation of special experimental techniques for diagnostics. The diagnostic set is the most scientifically intensive part of a plasma device. During many years of research operation some scientific tasks have been solved while new ones arose. New tasks often require significant changes in the diagnostic system, which is thus a very flexible part of plasma machines. Diagnostic systems are designed to solve several tasks. As an example here are the diagnostic tasks for the International Thermonuclear Experimental Reactor - ITER: (1) Measurements for machine protection and basic control; (2) Measurements for advanced control; (3) Additional measurements for performance evaluation and physics. Every new plasma machine is a further step along the path to the main goal - controlled fusion - and nobody knows in advance what new phenomena will be met on the way. So in the planning of diagnostic construction we should keep in mind further system upgrading to meet possible new scientific and technical challenges. (author)

  17. Molecular studies of Callithrix pygmaea (Primates, Platyrrhini based on transferrin intronic and ND1 regions: implications for taxonomy and conservation

    Directory of Open Access Journals (Sweden)

    Tagliaro Claudia Helena

    2000-01-01

    Full Text Available Traditional classifications of Platyrrhini monkeys, based mainly on morphological features, are being contested by recent molecular data. The subfamily Callitrichinae (Platyrrhini, Primates consists of a diverse group of species, many of them considered endangered. Our analysis of two DNA regions, a mtDNA gene (ND1 and a nuclear gene (intronic regions of the transferrin gene, suggests that Callithrix pygmaea may have sufficient variability to justify the existence of subspecies or even separate species. Phylogenetic dendrograms based on the ND1 region show that this species is more closely related to Amazonian than to Atlantic forest marmosets. These results reopen the discussion about diversity and conservation programs based exclusively on traditional classifications.

  18. Carbohydrate-deficient transferrin--a valid marker of alcoholism in population studies? Results from the Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Grønbaek, M; Becker, U; Henriksen, Jens Henrik Sahl

    1995-01-01

    Carbohydrate-deficient transferrin (CDT) was analyzed by a modified radioimmunoassay test in a random population sample of 400 individuals, and results were compared with reported alcohol intake derived from a structured questionnaire. Among the 180 men, the test was found to be acceptable...... with respect to detecting harmful alcohol intake (> 35 beverages/week) and alcohol intake above the recommended level (21 beverages/week), although the positive predictive values were low. Among the 220 women, the test was invalid with low predictive values. CDT was compared with other known markers of high...... alcohol intake, and it was observed that CDT had higher sensitivity and specificity than AST and short Michigan Alcoholism Screening Test (sMAST) in men, whereas the positive and negative predictive values were low in all tests. A combination of CDT and AST proved to be a better marker of both harmful...

  19. Therapy-resistant anaemia in congenital nephrotic syndrome of the Finnish type--implication of EPO, transferrin and transcobalamin losses.

    Science.gov (United States)

    Toubiana, Julie; Schlageter, Marie-Hélène; Aoun, Bilal; Dunand, Olivier; Vitkevic, Renata; Bensman, Albert; Ulinski, Tim

    2009-04-01

    Congenital nephrotic syndrome of the Finnish type (CNF) is due to NPHS1 mutation and is responsible for a variety of urinary protein losses. We report the case of a 4-month-old girl with a particularly severe form (proteinuria approximately 150 g/l) of CNF. She developed severe non-regenerative anaemia requiring bi-monthly blood transfusions despite daily EPO (600 UI/kg) and iron supplementation. Epoetin pharmacokinetics revealed a urinary loss of 27% of the given dose within the first 24 h after IV injection. However, plasma levels remained increased after 24 h (228 UI/l). Plasma transferrin and transcobalamin levels were undetectable. Atransferrinaemia and atranscobalaminaemia seem to be responsible for disturbed erythropoiesis.

  20. Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer

    Directory of Open Access Journals (Sweden)

    Gao W

    2017-02-01

    Full Text Available Wei Gao,1 Guihua Ye,1 Xiaochuan Duan,1 Xiaoying Yang,1 Victor C Yang1,2 1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics, School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA Abstract: The emergence of drug resistance is partially associated with overproduction of transferrin receptor (TfR. To overcome multidrug resistance (MDR and achieve tumor target delivery, we designed a novel biodegradable pH-sensitive micellar system modified with HAIYPRH, a TfR ligand (7pep. First, the polymers poly(l-histidine-coupled polyethylene glycol-2000 (PHIS-PEG2000 and 7pep-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (7pep-DSPE-PEG2000 were synthesized, and the mixed micelles were prepared by blending of PHIS-PEG2000 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG2000 or 7pep-DSPE-PEG2000 (7-pep HD micelles. The micelles exhibited good size uniformity, high encapsulation efficiency, and a low critical micelle concentration. By changing the polymer ratio in the micellar formulation, the pH response range was specially tailored to pH ~6.0. When loaded with antitumor drug doxorubicin (DOX, the micelle showed an acid pH-triggering drug release profile. The cellular uptake and cytotoxicity study demonstrated that 7-pep HD micelles could significantly enhance the intracellular level and antitumor efficacy of DOX in multidrug-resistant cells (MCF-7/Adr, which attributed to the synergistic effect of poly(l-histidine-triggered endolysosom escape and TfR-mediated endocytosis. Most importantly, the in vivo imaging study confirmed the targetability of 7-pep HD micelles to MDR tumor. These findings indicated that 7-pep HD micelles would be a promising drug delivery system in the treatment of drug

  1. Molecular mass spectrometry in metallodrug development: A case of mapping transferrin-mediated transformations for a ruthenium(III) anticancer drug

    Energy Technology Data Exchange (ETDEWEB)

    Jarosz, Maciej [Chair of Analytical Chemistry, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw (Poland); Matczuk, Magdalena, E-mail: mmatczuk@ch.pw.edu.pl [Chair of Analytical Chemistry, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw (Poland); Pawlak, Katarzyna [Chair of Analytical Chemistry, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw (Poland); Timerbaev, Andrei R. [Vernadsky Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, Kosygin St. 19, 119991 Moscow (Russian Federation)

    2014-12-03

    Highlights: • Extra- and intra-cellular interactions of Ru(III) anticancer drug candidate. • ESI-TOF-MS mapping of the ruthenium species bound to transferring. • ESI-QqQ-MS identification of released Ru species under cytosol simulated conditions. - Abstract: Electrospray ionization mass spectrometry (ESI-MS) techniques have been used to characterize the speciation of a Ru(III) anticancer drug, indazolium trans-[tetrachloridobis(1H-indazole) ruthenate(III)], upon its binding to transferrin and the impact of cellular reducing components on drug–transferrin adducts. Using time-of-flight ESI-MS, the polymorphism of apo- (iron-free) and holo-form (iron-saturated) of the protein was confirmed. While the ruthenium moieties bound to each of five isoforms under simulated extracellular conditions are essentially identical in numbers for apo- and holo-transferrin, distinct differences were found in the composition of Ru(III) species attached to either of the protein forms, which are dominated by differently coordinated aquated complexes. On the other hand, at least one of the Ru-N bonds in metal-organic framework remains intact even after prolonged interaction with the protein. Triple quadrupole tandem ESI-MS measurements demonstrated that the ruthenium species released from drug adducts with holo-transferrin in simulated cancer cytosol are underwent strong ligand exchange (as compared to the protein-bound forms) but most strikingly, they contain the metal center in the reduced Ru(II) state. In vitro probing the extra- and intracellular interactions of promising Ru(III) drug candidate performed by ESI-MS is thought to shed light on the transportation to tumor cells by transferrin and on the activation to more reactive species by the reducing environment of solid tumors.

  2. Low transferrin saturation is associated with impaired fasting glucose and insulin resistance in the South Korean adults: the 2010 Korean National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Park, R J; Moon, J D

    2015-05-01

    The associations of transferrin saturation with diabetes have not been well evaluated and conflicting results have been reported. The purpose of this study is to examine the association of iron indices (serum ferritin and transferrin saturation) with risk of impaired fasting glucose and insulin resistance. We conducted a cross-sectional study in 2413 individuals (1150 men and 1263 women) aged 20-50 years who participated in the 2010 Korean National Health and Nutrition Examination Survey. Participants were free of diabetes, malignancy, liver cirrhosis, chronic renal failure, anaemia, pregnancy and menopause. Fasting plasma glucose, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured as the outcomes. Impaired fasting glucose was more prevalent in the highest compared with the lowest serum ferritin quartile among men (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.20-3.24) after adjustment for multiple covariates. Following the same adjustment, impaired fasting glucose was less prevalent in the highest compared with the lowest transferrin saturation quartile among men (OR, 0.45; 95% CI, 0.25-0.80) and women (OR, 0.33; 95% CI, 0.14-0.77). Moreover, a higher ferritin level was significantly associated with higher HOMA-IR after adjusting for confounders in men. Lower transferrin saturation was also significantly associated with higher insulin levels and HOMA-IR in both sexes. Lower transferrin saturations were associated with an increased risk of impaired fasting glucose and insulin resistance among general South Korean population. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  3. Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody.

    Science.gov (United States)

    Pardridge, William M

    2015-02-01

    Biologic drugs are large molecules that do not cross the blood- brain barrier (BBB). Brain penetration is possible following the re-engineering of the biologic drug as an IgG fusion protein. The IgG domain is a MAb against an endogenous BBB receptor such as the transferrin receptor (TfR). The TfRMAb acts as a molecular Trojan horse to ferry the fused biologic drug into the brain via receptor-mediated transport on the endogenous BBB TfR. This review discusses TfR isoforms, models of BBB transport of transferrin and TfRMAbs, and the genetic engineering of TfRMAb fusion proteins, including BBB penetrating IgG-neurotrophins, IgG-decoy receptors, IgG-lysosomal enzyme therapeutics and IgG-avidin fusion proteins, as well as BBB transport of bispecific antibodies formed by fusion of a therapeutic antibody to a TfRMAb targeting antibody. Also discussed are quantitative aspects of the plasma pharmacokinetics and brain uptake of TfRMAb fusion proteins, as compared to the brain uptake of small molecules, and therapeutic applications of TfRMAb fusion proteins in mouse models of neural disease, including Parkinson's disease, stroke, Alzheimer's disease and lysosomal storage disorders. The review covers the engineering of TfRMAb-avidin fusion proteins for BBB targeted delivery of biotinylated peptide radiopharmaceuticals, low-affinity TfRMAb Trojan horses and the safety pharmacology of chronic administration of TfRMAb fusion proteins. The BBB delivery of biologic drugs is possible following re-engineering as a fusion protein with a molecular Trojan horse such as a TfRMAb. The efficacy of this technology will be determined by the outcome of future clinical trials.

  4. Comparison of colorimetry and electrothermal atomic absorption spectroscopy for the quantification of non-transferrin bound iron in human sera.

    Science.gov (United States)

    Jittangprasert, Piyada; Wilairat, Prapin; Pootrakul, Pensri

    2004-12-01

    This paper describes a comparison of two analytical techniques, one employing bathophenanthrolinedisulfonate (BPT), a most commonly-used reagent for Fe (II) determination, as chromogen and an electrothermal atomic absorption spectroscopy (ETAAS) for the quantification of non-transferrin bound iron (NTBI) in sera from thalassemic patients. Nitrilotriacetic acid (NTA) was employed as the ligand for binding iron from low molecular weight iron complexes present in the serum but without removing iron from the transferrin protein. After ultrafiltration the Fe (III)-NTA complex was then quantified by both methods. Kinetic study of the rate of the Fe (II)-BPT complex formation for various excess amounts of NTA ligand was also carried out. The kinetic data show that a minimum time duration (> 60 minutes) is necessary for complete complex formation when large excess of NTA is used. Calibration curves given by colorimetric and ETAAS methods were linear over the range of 0.15-20 microM iron (III). The colorimetric and ETAAS methods exhibited detection limit (3sigma) of 0.13 and 0.14 microM, respectively. The NTBI concentrations from 55 thalassemic serum samples measured employing BPT as chromogen were statistically compared with the results determined by ETAAS. No significant disagreement at 95% confidence level was observed. It is, therefore, possible to select any one of these two techniques for determination of NTBI in serum samples of thalassemic patients. However, the colorimetric procedure requires a longer analysis time because of a slow rate of exchange of NTA ligand with BPT, leading to the slow rate of formation of the colored complex.

  5. Diagnostic development

    International Nuclear Information System (INIS)

    Barnett, C.F.; Brisson, D.A.; Greco, S.E.

    1978-01-01

    During the past year the far-infrared or submillimeter diagnostic research program resulted in three major developments: (1) an optically pumped 0.385-μm D 2 O-laser oscillator-amplifier system was operated at a power level of 1 MW with a line width of less than 50 MHz; (2) a conical Pyrex submillimeter laser beam dump with a retention efficiency greater than 10 4 was developed for the ion temperature Thompson scattering experiment; and (3) a new diagnostic technique was developed that makes use of the Faraday rotation of a modulated submillimeter laser beam to determine plasma current profile. Measurements of the asymmetric distortion of the H/sub α/ (6563 A) spectral line profile show that the effective toroidal drift velocity, dv/sub two vertical bars i/dT/sub i/, may be used as an indicator of plasma quality and as a complement to other ion temperature diagnostics

  6. Molecular Beacons in Diagnostics

    OpenAIRE

    Tyagi, Sanjay; Kramer, Fred Russell

    2012-01-01

    Recent technical advances have begun to realize the potential of molecular beacons to test for diverse infections in clinical diagnostic laboratories. These include the ability to test for, and quantify, multiple pathogens in the same clinical sample, and to detect antibiotic resistant strains within hours. The design principles of molecular beacons have also spawned a variety of allied technologies.

  7. Pitfalls in diagnostic radiology

    Energy Technology Data Exchange (ETDEWEB)

    Peh, Wilfred C.G. (ed.) [Khoo Teck Puat Hospital (Singapore). Dept. of Diagnostic Radiology

    2015-04-01

    Only textbook to focus primarily on the topic of pitfalls in diagnostic radiology. Highlights the pitfalls in a comprehensive and systematic manner. Written by experts in different imaging modalities and subspecialties from reputable centers across the world. The practice of diagnostic radiology has become increasingly complex, with the use of numerous imaging modalities and division into many subspecialty areas. It is becoming ever more difficult for subspecialist radiologists, general radiologists, and residents to keep up with the advances that are occurring year on year, and this is particularly true for less familiar topics. Failure to appreciate imaging pitfalls often leads to diagnostic error and misinterpretation, and potential medicolegal problems. Diagnostic errors may be due to various factors such as inadequate imaging technique, imaging artifacts, failure to recognize normal structures or variants, lack of correlation with clinical and other imaging findings, and poor training or inexperience. Many, if not most, of these factors are potentially recognizable, preventable, or correctable. This textbook, written by experts from reputable centers across the world, systematically and comprehensively highlights the pitfalls that may occur in diagnostic radiology. Both pitfalls specific to different modalities and techniques and those specific to particular organ systems are described with the help of numerous high-quality illustrations. Recognition of these pitfalls is crucial in helping the practicing radiologist to achieve a more accurate diagnosis.

  8. Pitfalls in diagnostic radiology

    International Nuclear Information System (INIS)

    Peh, Wilfred C.G.

    2015-01-01

    Only textbook to focus primarily on the topic of pitfalls in diagnostic radiology. Highlights the pitfalls in a comprehensive and systematic manner. Written by experts in different imaging modalities and subspecialties from reputable centers across the world. The practice of diagnostic radiology has become increasingly complex, with the use of numerous imaging modalities and division into many subspecialty areas. It is becoming ever more difficult for subspecialist radiologists, general radiologists, and residents to keep up with the advances that are occurring year on year, and this is particularly true for less familiar topics. Failure to appreciate imaging pitfalls often leads to diagnostic error and misinterpretation, and potential medicolegal problems. Diagnostic errors may be due to various factors such as inadequate imaging technique, imaging artifacts, failure to recognize normal structures or variants, lack of correlation with clinical and other imaging findings, and poor training or inexperience. Many, if not most, of these factors are potentially recognizable, preventable, or correctable. This textbook, written by experts from reputable centers across the world, systematically and comprehensively highlights the pitfalls that may occur in diagnostic radiology. Both pitfalls specific to different modalities and techniques and those specific to particular organ systems are described with the help of numerous high-quality illustrations. Recognition of these pitfalls is crucial in helping the practicing radiologist to achieve a more accurate diagnosis.

  9. [Molecular genetic diagnostics and screening of hereditary hemochromatosis].

    Science.gov (United States)

    Zlocha, J; Kovács, L; Pozgayová, S; Kupcová, V; Durínová, S

    2006-06-01

    Hereditary hemochromatosis is considered one of the most common hereditary diseases in population of Caucasian origin. In recent years, a candidate gene for HLA-linked hemochromatosis, HFE, has been cloned, and a single G-to-A mutation resulting in a cysteine-to-tyrosine substitution (C282Y) has been identified in up to 80% of study patients with type 1 hereditary hemochromatosis. The purpose of the paper was to confirm the importance of genetic testing for HFE mutations in making the diagnosis of hemochromatosis and find out a suitable diagnostic algorithm for the indication of this form of diagnostics in patients suspected of hereditary hemochromatosis. The examination of C282Y mutation was conducted in 500 subjects. The most frequent indications for DNA analysis were hepatopathy of unknown ethiology, liver cirrhosis, diabetes mellitus, bronze skin pigmentation in connection with high serum iron concentration, elevated transferrin saturation and elevated serum ferritin levels. In our group of patients, 29 homozygotes and 75 heterozygotes for C282Y mutation were identified, 10 patients carried both C282Y and H63D mutations of HFE gene (compound heterozygotes), whereas in 386 subjects the mutation was not found. The genotype-phenotype correlation showed that 22 homozygotes had liver affection proved by imaging and/or histologic methods. Except the liver disorders, the most common symptoms of these patients were type 2 diabetes mellitus or glucose tolerance disorder (10 patients), arthritis or joint pain (9 patients) and cardiovascular disorders, such as cardiomyopathy (2 patients). Bronze skin pigmentation was present in 9 homozygotes. Transferin saturation values were significantly higher in homozygotes for C282Y mutation as compared to C282Y heterozygotes (p diagnostics of this severe, but in early recognition curable disease. Early detection and phlebotomy treatment prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily

  10. Diagnostic dilemma

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Dobrovolny, Robert; Nazarenko, Irina

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of a-galactosidase A (a-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased a-Gal A activity. However, in female heterozygotes, the a-Gal A activity can range from low t...... on enzyme replacement therapy. Thus, gene dosage analyses can detect large deletions (>50bp) in suspect heterozygotes for X-linked and autosomal dominant diseases that are "sequencing cryptic," resolving molecular diagnostic dilemmas....... to normal due to random X-chromosomal inactivation, and diagnostic confirmation requires identification of the family's a-Gal A gene mutation. In a young female who had occasional acroparesthesias, corneal opacities, and 15 to 50% of the lower limit of normal leukocyte a-Gal A activity, a-Gal A sequencing...... in two expert laboratories did not identify a confirmatory mutation, presenting a diagnostic dilemma. A renal biopsy proved diagnostic and renewed efforts to detect an a-Gal A mutation. Subsequent gene dosage analyses identified a large a-Gal A deletion confirming her heterozygosity, and she was started...

  11. Student Interpretations of Diagnostic Feedback

    Science.gov (United States)

    Doe, Christine

    2015-01-01

    Diagnostic assessment is increasingly being recognized as a potentially beneficial tool for teaching and learning (Jang, 2012). There have been calls in the research literature for students to receive diagnostic feedback and for researchers to investigate how such feedback is used by students. Therefore, this study examined how students…

  12. O potencial diagnóstico dos indicadores da obesidade centralizada The potential of central obesity antropometric indicators as diagnostic tools

    Directory of Open Access Journals (Sweden)

    Ignez Salas Martins

    2003-12-01

    com os fatores socioeconômicos, risco de desnutrição pregressa e com as alterações indicativas da síndrome metabólica do que a CC, mais associada aos fatores de risco para doenças cardiovasculares ateroscleróticas.OBJECTIVE: It has been suggested that the indicators of centralized obesity, namely by waist-to-hip circumference ratio (WHR and waistline measure (WM, express different metabolic disorders. Thus, a study was conducted in order to verify the diagnostic potential of the relationship between these two measures and social, behavioral, and biological determinants of centralized obesity. METHODS: Two hierarchical multiple regression models were applied to a 1,042 subject sample from the city of São Paulo, southeastern Brazil, in order to evaluate relationships between indicators and determinants for centralized obesity. Clinical, biochemical/laboratory, and behavioral surveys were carried out using standardized questionnaires. Evaluation included blood pressure, anthropometric measurements, and waistline and hip measures. RESULTS: WHR was significantly associated with low stature and strongly related to socioeconomic level; this was not the case with WM. Both WHR and WM were strongly associated with age, sex, and sedentary lifestyle. Women were at greater risk of centralized obesity then men: OR=5.04 and 7.27 for WHR and WM, respectively. WHR was significantly associated with alterations indicative of metabolic syndrome: hypertension and low levels of HDL-cholesterol. WM was significantly associated with hypertension alone. Both indicators were strongly associated with the concomitant presence of two or more alterations related to metabolic syndrome. Unlike WHR, WC was associated with hypercholesterolemia. CONCLUSIONS: WHR was more closely associated with socioeconomic factors, former risk of malnutrition, and alterations indicative of metabolic syndrome than WM, which was more closely associated with risk factors for cardiovascular and arteriosclerotic

  13. Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection.

    Science.gov (United States)

    Abo-Aziza, Faten A M; Hendawy, Seham H M; Namaky, Amira H El; Ashry, Heba M

    2017-06-01

    The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting profiles using prepared strongyles antigens. A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared strongyles antigens; crude somatic Strongylus vulgaris (CSS), excretory-secretory S. vulgaris (ESS), crude somatic Cyathostomins (CSC), and excretory-secretory Cyathostomins (ESC). The results revealed highest 437.04% and lowest 37.81% immunoglobulin G (IgG) in high and low egg shedder groups when using ESC and CSS antigens, respectively. Antibodies index for ESS and CSC were significantly higher in moderate egg shedder group while that for ESS and CSC, ESC was significantly higher in high egg shedder group. Tumor necrosis factor alpha (TNF-α)/interleukin-4 (IL-4) balance in S. vulgaris infected donkeys was approximately equal in apparently healthy, low and high egg shedder groups while TNF-α vulgaris and Cyathostomins spp. at the base of serological and molecular investigation.

  14. Improved image quality and diagnostic potential using ultra-high-resolution computed tomography of the lung with small scan FOV: A prospective study.

    Science.gov (United States)

    Zhu, Huiyuan; Zhang, Lian; Wang, Yali; Hamal, Preeti; You, Xiaofang; Mao, Haixia; Li, Fei; Sun, Xiwen

    2017-01-01

    The aim of this study was to assess whether CT imaging using an ultra-high-resolution CT (UHRCT) scan with a small scan field of view (FOV) provides higher image quality and helps to reduce the follow-up period compared with a conventional high-resolution CT (CHRCT) scan. We identified patients with at least one pulmonary nodule at our hospital from July 2015 to November 2015. CHRCT and UHRCT scans were conducted in all enrolled patients. Three experienced radiologists evaluated the image quality using a 5-point score and made diagnoses. The paired images were displayed side by side in a random manner and annotations of scan information were removed. The following parameters including image quality, diagnostic confidence of radiologists, follow-up recommendations and diagnostic accuracy were assessed. A total of 52 patients (62 nodules) were included in this study. UHRCT scan provides a better image quality regarding the margin of nodules and solid internal component compared to that of CHRCT (P images than of CHRCT images (Pimages (P 0.05). These findings suggest that the UHRCT prototype scanner provides a better image quality of subsolid nodules compared to CHRCT and contributes significantly to reduce the patients' follow-up period.

  15. Improved image quality and diagnostic potential using ultra-high-resolution computed tomography of the lung with small scan FOV: A prospective study.

    Directory of Open Access Journals (Sweden)

    Huiyuan Zhu

    Full Text Available The aim of this study was to assess whether CT imaging using an ultra-high-resolution CT (UHRCT scan with a small scan field of view (FOV provides higher image quality and helps to reduce the follow-up period compared with a conventional high-resolution CT (CHRCT scan. We identified patients with at least one pulmonary nodule at our hospital from July 2015 to November 2015. CHRCT and UHRCT scans were conducted in all enrolled patients. Three experienced radiologists evaluated the image quality using a 5-point score and made diagnoses. The paired images were displayed side by side in a random manner and annotations of scan information were removed. The following parameters including image quality, diagnostic confidence of radiologists, follow-up recommendations and diagnostic accuracy were assessed. A total of 52 patients (62 nodules were included in this study. UHRCT scan provides a better image quality regarding the margin of nodules and solid internal component compared to that of CHRCT (P 0.05. These findings suggest that the UHRCT prototype scanner provides a better image quality of subsolid nodules compared to CHRCT and contributes significantly to reduce the patients' follow-up period.

  16. Diagnostic potential of Fasciola gigantica-derived 14.5 kDa fatty acid binding protein in the immunodiagnosis of bubaline fascioliasis.

    Science.gov (United States)

    Allam, G; Bauomy, I R; Hemyeda, Z M; Diab, T M; Sakran, T F

    2013-06-01

    The 14.5 kDa fatty acid binding protein (FABP) was isolated from the crude extract of adult Fasciola gigantica worms. Polyclonal anti-FABP IgG was generated in rabbits immunized with prepared FABP antigen. Sandwich enzyme-linked immunosorbent assay (ELISA) was applied to detect coproantigen in stools and circulating Fasciola antigen (CA) in sera of 126 water buffaloes by using purified and horseradish peroxidase (HRP)-conjugated anti-FABP IgG. Sandwich ELISA sensitivity was 96.97% and 94.95%; while specificity was 94.12% and 82.35% for coproantigen and CA detection, respectively. However, sensitivity and specificity of the Kato-Katz technique was 73.74% and 100%, respectively. The diagnostic efficacy of sandwich ELISA was 96.55% and 93.1% for coproantigen and CA detection, respectively. In contrast, the diagnostic efficacy of the Kato-Katz technique was 77.59%. In conclusion, these results demonstrate that the purified 14.5 kDa FABP provides a more suitable antigen for immunodiagnosis of early and current bubaline fascioliasis by using sandwich ELISA.

  17. Disseminated Acanthamoeba Infection Presenting With Cutaneous Lesions in an Immunocompromised Patient: A Case Report, Review of Histomorphologic Findings, and Potential Diagnostic Pitfalls.

    Science.gov (United States)

    Morrison, Annie O; Morris, Robert; Shannon, Amie; Lauer, Scott R; Guarner, Jeannette; Kraft, Colleen S

    2016-02-01

    Free-living amoebas are exceedingly rare causes of cutaneous infections and present unique diagnostic and therapeutic challenges. We describe a case of disseminated acanthamoebiasis with cutaneous manifestations and summarize additional diagnostic, prognostic, and therapeutic highlights. A 58-year-old man with relapsed chronic lymphocytic leukemia had several weeks of progressive, painful ulcerations on the forehead, arms, abdomen, and thighs. A biopsy was performed for histopathologic evaluation. The biopsy specimen showed inflammatory infiltrate with abscess formation involving the epidermis, dermis, and subcutis. Scattered cells showed nuclei with a prominent central karyosome, dispersed chromatin, and either abundant foamy basophilic cytoplasm or two well-demarcated cytoplasmic walls. Acanthamoeba species was confirmed by polymerase chain reaction from the formalin-fixed, paraffin-embedded tissue. Cutaneous lesions from acanthamoebiasis are exceptionally rare but should be included in the differential diagnosis of necrotic cutaneous lesions in immunocompromised patients. Although infrequently encountered, pathologists need to be aware of the morphologic features of free-living amoebas. Immunohistochemical and molecular studies can confirm the diagnosis. Multiagent treatment regimens, when initiated empirically, have been more successful than single-agent regimens, but infections involving the central nervous system are almost universally fatal. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Metabolomics for laboratory diagnostics.

    Science.gov (United States)

    Bujak, Renata; Struck-Lewicka, Wiktoria; Markuszewski, Michał J; Kaliszan, Roman

    2015-09-10

    Metabolomics is an emerging approach in a systems biology field. Due to continuous development in advanced analytical techniques and in bioinformatics, metabolomics has been extensively applied as a novel, holistic diagnostic tool in clinical and biomedical studies. Metabolome's measurement, as a chemical reflection of a current phenotype of a particular biological system, is nowadays frequently implemented to understand pathophysiological processes involved in disease progression as well as to search for new diagnostic or prognostic biomarkers of various organism's disorders. In this review, we discussed the research strategies and analytical platforms commonly applied in the metabolomics studies. The applications of the metabolomics in laboratory diagnostics in the last 5 years were also reviewed according to the type of biological sample used in the metabolome's analysis. We also discussed some limitations and further improvements which should be considered taking in mind potential applications of metabolomic research and practice. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection

    Directory of Open Access Journals (Sweden)

    Faten A. M. Abo-Aziza

    2017-06-01

    Full Text Available Aim: The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE and western blotting profiles using prepared strongyles antigens. Materials and Methods: A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared strongyles antigens; crude somatic Strongylus vulgaris (CSS, excretory-secretory S. vulgaris (ESS, crude somatic Cyathostomins (CSC, and excretory-secretory Cyathostomins (ESC. Results: The results revealed highest 437.04% and lowest 37.81% immunoglobulin G (IgG in high and low egg shedder groups when using ESC and CSS antigens, respectively. Antibodies index for ESS and CSC were significantly higher in moderate egg shedder group while that for ESS and CSC, ESC was significantly higher in high egg shedder group. Tumor necrosis factor alpha (TNF-α/interleukin-4 (IL-4 balance in S. vulgaris infected donkeys was approximately equal in apparently healthy, low and high egg shedder groups while TNF-α < IL-4 in moderate egg shedder. In Cyathostomins infected animals, TNF-α/IL-4 balance was approximately equal in apparently healthy group while it was low in moderate and high egg shedder groups. The diagnostic accuracy showed that the higher specificity (46.6% and prevalence (95.40% were recorded by CSS and ESC antigens, respectively. However, SDS-PAGE and western blotting profiling proved that the band at molecular weight 25 kDa is exhibited by CSS antigen. Conclusion: Combination of detecting level of TNF-α/IL-4 balance, CSS antigen and IgG concentration is good tool for appropriate diagnosis of such infection. More advancement research must be

  20. Polymethyl methacrylate-co-methacrylic acid coatings with controllable concentration of surface carboxyl groups: A novel approach in fabrication of polymeric platforms for potential bio-diagnostic devices

    Energy Technology Data Exchange (ETDEWEB)

    Hosseini, Samira; Ibrahim, Fatimah [Center for Innovation in Medical Engineering, Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603 (Malaysia); Djordjevic, Ivan, E-mail: ivan.djordjevic@um.edu.my [Center for Innovation in Medical Engineering, Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603 (Malaysia); Koole, Leo H. [Center for Innovation in Medical Engineering, Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603 (Malaysia); Department of Biomedical Engineering, Faculty of Health. Medicine and Life Science, Maastricht University, PO Box 616, NL 6200 MD Maastricht (Netherlands)

    2014-05-01

    Highlights: • Synthesis and processing of PMMA-co-MAA spin-coatings on silicon wafers. • Surface chemistry and morphology as a function of tailored co-polymer structure. • Polymer coatings with controlled number of surface carboxyl groups. - Abstract: The generally accepted strategy in development of bio-diagnostic devices is to immobilize proteins on polymeric surfaces as a part of detection process for diseases and viruses through antibody/antigen coupling. In that perspective, polymer surface properties such as concentration of functional groups must be closely controlled in order to preserve the protein activity. In order to improve the surface characteristics of transparent polymethacrylate plastics that are used for diagnostic devices, we have developed an effective fabrication procedure of polymethylmetacrylate-co-metacrylic acid (PMMA-co-MAA) coatings with controlled number of surface carboxyl groups. The polymers were processed effectively with the spin-coating technique and the detailed control over surface properties is here by demonstrated through the variation of a single synthesis reaction parameter. The chemical structure of synthesized and processed co-polymers has been investigated with nuclear magnetic resonance spectroscopy (NMR) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-ToF-MS). The surface morphology of polymer coatings have been analyzed with atomic force microscopy (AFM) and scanning electron microscopy (SEM). We demonstrate that the surface morphology and the concentration of surface –COOH groups (determined with UV–vis surface titration) on the processed PMMA-co-MAA coatings can be precisely controlled by variation of initial molar ratio of reactants in the free-radical polymerization reaction. The wettability of developed polymer surfaces also varies with macromolecular structure.

  1. Polymethyl methacrylate-co-methacrylic acid coatings with controllable concentration of surface carboxyl groups: A novel approach in fabrication of polymeric platforms for potential bio-diagnostic devices

    International Nuclear Information System (INIS)

    Hosseini, Samira; Ibrahim, Fatimah; Djordjevic, Ivan; Koole, Leo H.

    2014-01-01

    Highlights: • Synthesis and processing of PMMA-co-MAA spin-coatings on silicon wafers. • Surface chemistry and morphology as a function of tailored co-polymer structure. • Polymer coatings with controlled number of surface carboxyl groups. - Abstract: The generally accepted strategy in development of bio-diagnostic devices is to immobilize proteins on polymeric surfaces as a part of detection process for diseases and viruses through antibody/antigen coupling. In that perspective, polymer surface properties such as concentration of functional groups must be closely controlled in order to preserve the protein activity. In order to improve the surface characteristics of transparent polymethacrylate plastics that are used for diagnostic devices, we have developed an effective fabrication procedure of polymethylmetacrylate-co-metacrylic acid (PMMA-co-MAA) coatings with controlled number of surface carboxyl groups. The polymers were processed effectively with the spin-coating technique and the detailed control over surface properties is here by demonstrated through the variation of a single synthesis reaction parameter. The chemical structure of synthesized and processed co-polymers has been investigated with nuclear magnetic resonance spectroscopy (NMR) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-ToF-MS). The surface morphology of polymer coatings have been analyzed with atomic force microscopy (AFM) and scanning electron microscopy (SEM). We demonstrate that the surface morphology and the concentration of surface –COOH groups (determined with UV–vis surface titration) on the processed PMMA-co-MAA coatings can be precisely controlled by variation of initial molar ratio of reactants in the free-radical polymerization reaction. The wettability of developed polymer surfaces also varies with macromolecular structure

  2. Identification of ISMyo2, a novel insertion sequence element of IS21 family and its diagnostic potential for detection of Mycobacterium yongonense.

    Science.gov (United States)

    Kim, Byoung-Jun; Kim, Kijeong; Kim, Bo-Ram; Kook, Yoon-Hoh; Kim, Bum-Joon

    2015-10-15

    Mycobacterium yongonense, as a novel member of the M. avium complex (MAC), was recently reported to be isolated from human specimens in South Korea and Italy. Due to its close relatedness to other MAC members, particularly M. intracellulare in taxonomic aspects, the development of a novel diagnostic method for its specific detection is necessary for clinical or epidemiologic purposes. Using the Mycobacterium yongonense genome information, we have identified a novel IS-element, ISMyo2. Targeting the ISMyo2 sequence, we developed a real-time PCR method and applied the technique to Mycobacterial genomic DNA. To identify proper nucleic acid targets for the diagnosis, comparisons of all insertion sequence (IS) elements of 3 M. intracellulare and 3 M. yongonense strains, whose complete genome sequences we reported recently, led to the selection of a novel target gene, the M. yongonense-specific IS element, ISMyo2 (2,387 bp), belonging to the IS21 family. Next, we developed a real-time PCR method using SYBR green I for M. yongonense-specific detection targeting ISMyo2, producing a 338-bp amplicon. When this assay was applied to 28 Mycobacterium reference strains and 63 MAC clinical isolates, it produced amplicons in only the 6 M. yongonense strains, showing a sensitivity of 100 fg of genomic DNA, suggesting its feasibility as a diagnostic method for M. yongonense strains. We identified a novel ISMyo2 IS element belonging to the IS21 family specific to M. yongonense strains via genome analysis, and a real-time PCR method based on its sequences was developed.

  3. A novel quantification strategy of transferrin and albumin in human serum by species-unspecific isotope dilution laser ablation inductively coupled plasma mass spectrometry (ICP-MS)

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Liuxing, E-mail: fenglx@nim.ac.cn; Zhang, Dan; Wang, Jun; Shen, Dairui; Li, Hongmei

    2015-07-16

    Highlights: • Species-unspecific ID-PAGE-LA-ICP-MS was used to quantify Alb and Tf in human serum. • Addition methods of species-unspecific {sup 34}S spike were evaluated. • Isotope change conditions were investigated to reach satisfactory “isotope equilibration”. • Human serum CRM (ERM-DA470k/IFCC) was used to validate the new arrangements. • The developed method offers potential for accurate quantification of protein by ID-PAGE-LA-ICP-MS. - Abstract: Species-specific (SS) isotope dilution analysis with gel electrophoresis (GE)-laser ablation (LA)-ICP-MS is a promising technique for the quantification of particular metal-binding proteins in biological samples. However, unavailable isotopically enriched spike and metal losses in GE separation are main limitations for SS-isotope dilution PAGE-LA-ICP-MS. In this study, we report for the first time the absolute quantification of transferrin (Tf) and albumin (Alb) in human serum by non-denaturing (native) GE combined with species-unspecific isotope dilution mass spectrometry (IDMS). In order to achieve a homogeneous distribution of both protein and isotope-enriched spike (simulated isotope equilibration), immersing the protein strips with {sup 34}S spike solution after gel electrophoresis was demonstrated to be an effective way of spike addition. Furthermore, effects of immersion time and {sup 34}S spike concentration were investigated to obtain optimal conditions of the post-electrophoresis isotope dilution method. The relative mass of spike and ablated sample (m{sub sp}/m{sub sam}) in IDMS equation was calculated by standard Tf and Alb proteins, which could be applied to the quantification of Tf and Alb in ERM-DA470k/IFCC for method confirmation. The results were in agreement with the certified value with good precision and small uncertainty (1.5–3%). In this method, species-specific spike protein is not necessary and the integrity of the heteroatom-protein could be maintained in sample preparation

  4. A novel quantification strategy of transferrin and albumin in human serum by species-unspecific isotope dilution laser ablation inductively coupled plasma mass spectrometry (ICP-MS)

    International Nuclear Information System (INIS)

    Feng, Liuxing; Zhang, Dan; Wang, Jun; Shen, Dairui; Li, Hongmei

    2015-01-01

    Highlights: • Species-unspecific ID-PAGE-LA-ICP-MS was used to quantify Alb and Tf in human serum. • Addition methods of species-unspecific 34 S spike were evaluated. • Isotope change conditions were investigated to reach satisfactory “isotope equilibration”. • Human serum CRM (ERM-DA470k/IFCC) was used to validate the new arrangements. • The developed method offers potential for accurate quantification of protein by ID-PAGE-LA-ICP-MS. - Abstract: Species-specific (SS) isotope dilution analysis with gel electrophoresis (GE)-laser ablation (LA)-ICP-MS is a promising technique for the quantification of particular metal-binding proteins in biological samples. However, unavailable isotopically enriched spike and metal losses in GE separation are main limitations for SS-isotope dilution PAGE-LA-ICP-MS. In this study, we report for the first time the absolute quantification of transferrin (Tf) and albumin (Alb) in human serum by non-denaturing (native) GE combined with species-unspecific isotope dilution mass spectrometry (IDMS). In order to achieve a homogeneous distribution of both protein and isotope-enriched spike (simulated isotope equilibration), immersing the protein strips with 34 S spike solution after gel electrophoresis was demonstrated to be an effective way of spike addition. Furthermore, effects of immersion time and 34 S spike concentration were investigated to obtain optimal conditions of the post-electrophoresis isotope dilution method. The relative mass of spike and ablated sample (m sp /m sam ) in IDMS equation was calculated by standard Tf and Alb proteins, which could be applied to the quantification of Tf and Alb in ERM-DA470k/IFCC for method confirmation. The results were in agreement with the certified value with good precision and small uncertainty (1.5–3%). In this method, species-specific spike protein is not necessary and the integrity of the heteroatom-protein could be maintained in sample preparation process. Moreover, the

  5. The impact of maternal obesity on iron status, placental transferrin receptor expression and hepcidin expression in human pregnancy.

    Science.gov (United States)

    Garcia-Valdes, L; Campoy, C; Hayes, H; Florido, J; Rusanova, I; Miranda, M T; McArdle, H J

    2015-04-01

    Obesity is associated with decreased iron status, possibly due to a rise in hepcidin, an inflammatory protein known to reduce iron absorption. In animals, we have shown that maternal iron deficiency is minimised in the foetus by increased expression of placental transferrin receptor (pTFR1), resulting in increased iron transfer at the expense of maternal iron stores. This study examines the effect of obesity during pregnancy on maternal and neonatal iron status in human cohorts and whether the placenta can compensate for decreased maternal iron stores by increasing pTFR1 expression. A total of 240 women were included in this study. One hundred and fifty-eight placentas (Normal: 90; Overweight: 37; Obese: 31) were collected at delivery. Maternal iron status was measured by determining serum transferrin receptor (sTFR) and ferritin levels at 24 and 34 weeks and at delivery. Hepcidin in maternal and cord blood was measured by ELISA and pTFR1 in placentas by western blotting and real-time RT-PCR. Low iron stores were more common in obese women. Hepcidin levels (ng ml(-1)) at the end of the pregnancy were higher in obese than normal women (26.03±12.95 vs 18.00±10.77, PMaternal hepcidin levels were correlated with maternal iron status (sTFR r=0.2 P=0.025), but not with neonatal values. mRNA and protein levels of pTFR1 were both inversely related to maternal iron status. For mRNA and all women, sTFR r=0.2 P=0.044. Ferritin mRNA levels correlated only in overweight women r=-0.5 P=0.039 with hepcidin (r=0.1 P=0.349), irrespective of maternal body mass index (BMI). The data support the hypothesis that obese pregnant women have a greater risk of iron deficiency and that hepcidin may be a regulatory factor. Further, we show that the placenta responds to decreased maternal iron status by increasing pTFR1 expression.

  6. [Iron status with particular consideration of soluble transferrin receptors in children and youth with gastritis, with or without Helicobacter pylori infection].

    Science.gov (United States)

    Mierzwa, Grazyna; Augustyńska, Beata; Czerwionka-Szaflarska, Mieczysława; Tyrakowski, Tomasz

    2006-09-01

    Role of Helicobacter pylori infection in chronic gastritis and gastric and/or duodenal ulcers is well known. Simultaneously there are some articles in literature considering H. pylori as a cause of extra-gastrointestinal illnesses such as atopic dermatitis, chronic urticaria or acne rosacea, hypotrophy, Schoenlein-Henoch disease, atherosclerosis or hypochromic anaemia. The aim of the study. was to asses iron status in aspect of plasmatic transferrin receptors concentration among children and youth with chronic gastritis with or without Helicobacter pylori infection. Forty one patients were included as a study group. Range of age was 9-18 years. All patients were diagnosed due to chronic abdominal pains. There were 13 males and 28 females. Blood was collected from every patient for blood cell count, iron, transferrin and transferrin receptors concentration (sTfR) assessment before endoscopy of upper gastrointestinal tract. Concentration of sTfR was higher than age norm among 29 (71%) of patients. Among patients with higher level of sTfR 20 (69%) had normal haemoglobin concentration and in this group 10 patients had H. pylori infection. During analysis of 12 patients with nornal level of sTfR normal haemoglobin concentration was found and among five of them H. pylori infection was stated. Among 21 patients without H. pylori infection 14 had normal level of sTfR and 7 had higher level of sTfR which means that 33% had hidden iron deficiency (involuntary of normal Hb concentrations). Among 15 of 20 patients with H. pylori infection level of sTfR was higher which means that 75% patients with infection had hidden iron deficiency (involuntary of normal Hb concentrations). Level of plasmatic transferrin receptors can be good and sensitive indicator of iron deficiency and can be helpful in differential diagnosis of hypochromic anaemia and anaemia caused by chronic illness including chronic gastritis with Helicobacter pylori infection.

  7. Time- and cell-type specific changes in iron, ferritin, and transferrin in the gerbil hippocampal CA1 region after transient forebrain ischemia

    Directory of Open Access Journals (Sweden)

    Dae Young Yoo

    2016-01-01

    Full Text Available In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin (ferritin-H, and transferrin in the gerbil hippocampal CA1 region from 30 minutes to 7 days following transient forebrain ischemia. Relative to sham controls, iron reactivity increased significantly in the stratum pyramidale and stratum oriens at 12 hours following ischemic insult, transiently decreased at 1-2 days and then increased once again within the CA1 region at 4-7 days after ischemia. One day after ischemia, ferritin-H immunoreactivity increased significantly in the stratum pyramidale and decreased at 2 days. At 4-7 days after ischemia, ferritin-H immunoreactivity in the glial components in the CA1 region was significantly increased. Transferrin immunoreactivity was increased significantly in the stratum pyramidale at 12 hours, peaked at 1 day, and then decreased significantly at 2 days after ischemia. Seven days after ischemia, Transferrin immunoreactivity in the glial cells of the stratum oriens and radiatum was significantly increased. Western blot analyses supported these results, demonstrating that compared to sham controls, ferritin H and transferrin protein levels in hippocampal homogenates significantly increased at 1 day after ischemia, peaked at 4 days and then decreased. These results suggest that iron overload-induced oxidative stress is most prominent at 12 hours after ischemia in the stratum pyramidale, suggesting that this time window may be the optimal period for therapeutic intervention to protect neurons from ischemia-induced death.

  8. Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition?

    Science.gov (United States)

    Büyükkaragöz, Bahar; Akgun, Necat A; Bulus, Ayse D; Durmus Aydogdu, Sultan; Bal, Cengiz

    2017-04-01

    To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). Infants with hemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30). Following anemia and malnutrition treatment, tests were repeated. Besides hematological indices compatible with IDA, serum iron (Fe) and transferrin saturation (TS) were significantly lower, while transferrin was significantly higher in MA and A groups compared to controls (p 0.05) and significantly higher than controls (p iron treatment, sTfR decreased in both MA and A groups (p iron treatment, we believe that this parameter was not influenced by MAM or inflammation; and it alone can be used to detect IDA and monitor treatment response in infants with MAM.

  9. A new generation of optical diagnostics for bladder cancer: technology, diagnostic accuracy, and future applications

    NARCIS (Netherlands)

    Cauberg, Evelyne C. C.; de Bruin, Daniël M.; Faber, Dirk J.; van Leeuwen, Ton G.; de La Rosette, Jean J. M. C. H.; de Reijke, Theo M.

    2009-01-01

    CONTEXT: New developments in optical diagnostics have a potential for less invasive and improved detection of bladder cancer. OBJECTIVE: To provide an overview of the technology and diagnostic yield of recently developed optical diagnostics for bladder cancer and to outline their potential future

  10. The Use of Soluble Transferrin Receptor in the Detection of rHuEPO abuse in Sports

    Directory of Open Access Journals (Sweden)

    Donovan McGrowder

    2010-01-01

    Full Text Available Erythropoietin (EPO increases the number of circulating erythrocytes and muscle oxygenation. The recombinant forms of EPO have indiscriminately been used by athletes, mainly in endurance sports to increase their erythrocytes concentration, thus generating a better delivery of oxygen to the muscle tissue. The administration of recombinant human erythropoietin (rHuEPO except for therapeutic use was prohibited by the International Olympic Committee (IOC and its unauthorized use considered as doping. In the last few years, a number of studies using parameters indicative of accelerated erythropoiesis have investigated a number of indirect methods for the detection of rHuEPO abuse. No single indirect marker has been found that can satisfactorily demonstrated rHuEPO misuse. Soluble transferrin receptor (sTfR is a new marker of iron status and erythropoietic activity. It has been included in multivariable blood testing models for the detection of performance enhancing EPO abuse in sports. Indirect markers of altered erythropoiesis give reliable evidence of current or discontinued rHuEPO usage. This review describes the physical, biological and pharmacokinetic properties of endogenous EPO and its recombinant form. It also discusses the available strategies for the detection of rHuEPO abuse in sports, involving the use of sTfR concentration directly or in mathematical multivariate models.

  11. Transferrin-conjugated magnetic dextran-spermine nanoparticles for targeted drug transport across blood-brain barrier.

    Science.gov (United States)

    Ghadiri, Maryam; Vasheghani-Farahani, Ebrahim; Atyabi, Fatemeh; Kobarfard, Farzad; Mohamadyar-Toupkanlou, Farzaneh; Hosseinkhani, Hossein

    2017-10-01

    Application of many vital hydrophilic medicines have been restricted by blood-brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran-spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS-NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested. The superparamagnetic characteristic of TDS-NPs was verified by vibration simple magnetometer. Capecitabine loaded TDS-NPs exhibited pH-sensitive release behavior with enhanced cytotoxicity against U87MG cells, compared to DS-NPs and free capecitabine. Prussian-blue staining and TEM-imaging showed the significant cellular uptake of TDS-NPs. Furthermore, a remarkable increase of Fe concentrations in brain was observed following their biodistribution and histological studies in vivo, after 1 and 7 days of post-injection. Enhanced drug transport across BBB and pH-triggered cellular uptake of TDS-NPs indicated that these theranostic nanocarriers are promising candidate for the brain malignance treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2851-2864, 2017. © 2017 Wiley Periodicals, Inc.

  12. A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas.

    Science.gov (United States)

    Li, Yan; He, Hai; Jia, Xinru; Lu, Wan-Liang; Lou, Jinning; Wei, Yen

    2012-05-01

    A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Nanodevices in diagnostics

    Science.gov (United States)

    Hu, Ye; Fine, Daniel H.; Tasciotti, Ennio; Bouamrani, Ali; Ferrari, Mauro

    2010-01-01

    The real-time, personalized and highly sensitive early-stage diagnosis of disease remains an important challenge in modern medicine. With the ability to interact with matter at the nanoscale, the development of nanotechnology architectures and materials could potentially extend subcellular and molecular detection beyond the limits of conventional diagnostic modalities. At the very least, nanotechnology should be able to dramatically accelerate biomarker discovery, as well as facilitate disease monitoring, especially of maladies presenting a high degree of molecular and compositional heterogeneity. This article gives an overview of several of the most promising nanodevices and nanomaterials along with their applications in clinical practice. Significant work to adapt nanoscale materials and devices to clinical applications involving large interdisciplinary collaborations is already underway with the potential for nanotechnology to become an important enabling diagnostic technology. PMID:20229595

  14. Giant teratoma of anterior mediastinum in a 14-year-old girl as an example of potential diagnostic problems and errors

    Directory of Open Access Journals (Sweden)

    Przemysław Wolak

    2013-10-01

    Full Text Available Teratomas are tumors originating from the three primary germ layers, most commonly located within gonads or in the sacral region. Chest locations are rare. Mediastinal teratoma showing no tumor-specific symptoms may be treated as exudative pneumonia. The goal of the article was to present a case encountered in our practice as a showcase of possible diagnostic problems and errors. Despite a thorough medical examination with additional exams (ultrasound scans of pleural cavities, chest X-ray and laboratory analyses, the diagnosis of a thoracic tumor was made only after chest computed tomography scan was performed following ineffective attempts at antibiotic therapy and pleural drainage. Following the diagnosis of mediastinal tumor, the patient was subjected to surgery. A giant teratoma (confirmed in histopathological examination was removed upon left-sided thoracotomy. Following the procedure, lung expansion and patient recovery were observed. Computed tomography of the chest should be performed routinely upon encountering difficulties in the treatment of exudative pneumonia in children. In every case of pneumonia with pleural effusion in children, inflammatory mask of mediastinal tumors should be ruled out.

  15. A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer

    International Nuclear Information System (INIS)

    Perez, Amparo; Loizaga, Ana; Arceo, Raquel; Lacasa, Isabel; Rabade, Ainara; Zorroza, Kerman; Mosen-Ansorena, David; Gonzalez, Esperanza; Aransay, Ana M.; Falcon-Perez, Juan M.; Unda-Urzaiz, Miguel; Royo, Felix

    2014-01-01

    Bladder cancer is one of the most common cancers and, together with prostate carcinoma, accounts for the majority of the malignancies of the genitourinary tract. Since prognosis ameliorates with early detection, it will be beneficial to have a repertoire of diagnostic markers that could complement the current diagnosis protocols. Recently, cell-secreted extracellular vesicles have received great interest as a source of low invasive disease biomarkers because they are found in many body fluids, including urine. The current work describes a pilot study to generate an array-based catalogue of mRNA associated to urinary vesicles, and also a comparison with samples obtained from bladder cancer patients. After an analysis of presence/absence of transcripts in bladder cancer EVs, a list of genes was selected for further validation using PCR technique. We found four genes differentially expressed in cancer samples. LASS2 and GALNT1 were present in cancer patients, while ARHGEF39 and FOXO3 were found only in non-cancer urinary vesicles. Previous studies have pointed to the involvement of those genes in tumour progression and metastasis

  16. Over-Expression of Dopamine D2 Receptor and Inwardly Rectifying Potassium Channel Genes in Drug-Naive Schizophrenic Peripheral Blood Lymphocytes as Potential Diagnostic Markers

    Directory of Open Access Journals (Sweden)

    Ágnes Zvara

    2005-01-01

    Full Text Available Schizophrenia is one of the most common neuropsychiatric disorders affecting nearly 1% of the human population. Current diagnosis of schizophrenia is based on complex clinical symptoms. The use of easily detectable peripheral molecular markers could substantially help the diagnosis of psychiatric disorders. Recent studies showed that peripheral blood lymphocytes (PBL express subtypes of D1 and D2 subclasses of dopamine receptors. Recently, dopamine receptor D3 (DRD3 was found to be over-expressed in schizophrenic PBL and proposed to be a diagnostic and follow-up marker for schizophrenia. In this study we screened PBL of 13 drug-naive/drug-free schizophrenic patients to identify additional markers of schizophrenia. One of the benefits of our study is the use of blood samples of non-medicated, drug-naive patients. This excludes the possibility that changes detected in gene expression levels might be attributed to the medication rather than to the disorder itself. Among others, genes for dopamine receptor D2 (DRD2 and the inwardly rectifying potassium channel (Kir2.3 were found to be over-expressed in microarray analysis. Increased mRNA levels were confirmed by quantitative real-time PCR (QRT-PCR using the SybrGreen method and dual labeled TaqMan probes. The use of both molecular markers allows a more rapid and precise prediction of schizophrenia and might help find the optimal medication for schizophrenic patients.

  17. [Cultural detection of thermotolerant Campylobacter spp. in food--potentials and limitations of diagnostic tools in the context of official food control].

    Science.gov (United States)

    Messelhäusser, Ute; Thärigen, Diana; Fella, Christiane; Schreiner, Hermann; Busch, Ulrich; Höller, Christiane

    2015-01-01

    Thermotolerant Campylobacter spp. rank among the most important foodborne pathogens in Germany. Therefore a necessity for rapid and routinely useable detection methods exists also in the area of food microbiology. A reliable, cultura qualitative, but also quantitative detection of thermotolerant Campylobacter spp. pose a challenge, at least concerning special food matrices, especially because in the context of official food control the cultural detection of thermotolerant Campylobacter spp. is needed. This was the reason, why different cultural detection methods, beside the standard procedure of ISO 10272:2006, in combination with molecular and immunological screening methods were tested at the Bavarian Health and Food Safety Authority (LGL) during the last years for the use in routine diagnostic using different food matrices of animal and plant origin. The results of the comparative studies showed clearly that no enrichment broth tested gave completely satisfactory results for an only culture-based detection the combination with a screening method is therefore recommended for a rapid and reliable detection. But in this case the user should take into account that the sensitivity of such molecular and immunological methods is normally so high that in some cases, depending on the food matrix and processing step, the isolation of the pathogen would not be possible in samples, which were positive in the screening methods.

  18. Potential of confocal laser scanning microscopy for non-invasive diagnostics of malignant epithelial skin tumors in the course of dermatoheliosis progression

    Directory of Open Access Journals (Sweden)

    E. S. Snarskaya

    2016-01-01

    Full Text Available Most cases of malignant epithelial skin neoplasms including actinic keratosis and basal cell carcinoma, which are characterized by the most complicated course and numerous clinical and morphological options, involve dermatoheliosis progression. The risk of actinic keratosis transformation into basal cell carcinoma varies from 0.1% to 20% and up to 80% in cases of multiple AK lesion foci. A non-invasive method known as reflectance confocal laser scanning microscopy is the most promising one for the purposes of early diagnostics of signs pointing at epithelial skin neoplasm development and makes it possible to monitor the tumor in progress in vivo to diagnose the presence of a pool of squamous cells on a timely basis. The confocal laser scanning microscopy method provides high-contrast images of for any horizontal-oriented morphologic structures in the epidermis and upper dermis with a resolution comparable to those characteristic of traditional optical microscopy of skin tissue samples. According to our data obtained as a result of studying dynamic changes and morphologic structures in actinic keratosis foci (50 cases using the confocal laser scanning microscopy method, we discovered a number of morphologic features, and their further analysis will distinguish the signs of progressing carcinogenesis in case of dermatoheliosis.

  19. A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Amparo; Loizaga, Ana; Arceo, Raquel; Lacasa, Isabel; Rabade, Ainara [Urology Service, Basurto University Hospital, Bilbao 48013, Bizkaia (Spain); Zorroza, Kerman [Basque Foundation for Health Innovation and Research (BIOEF), DNA Laboratory, Basurto Hospital, Bilbao 48013, Bizkaia (Spain); Mosen-Ansorena, David [Genome Analysis Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); Gonzalez, Esperanza [Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); Aransay, Ana M. [Genome Analysis Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); Falcon-Perez, Juan M. [Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao 48011, Bizkaia (Spain); Unda-Urzaiz, Miguel [Urology Service, Basurto University Hospital, Bilbao 48013, Bizkaia (Spain); Royo, Felix, E-mail: froyo.ciberehd@cicbiogune.es [Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain)

    2014-01-22

    Bladder cancer is one of the most common cancers and, together with prostate carcinoma, accounts for the majority of the malignancies of the genitourinary tract. Since prognosis ameliorates with early detection, it will be beneficial to have a repertoire of diagnostic markers that could complement the current diagnosis protocols. Recently, cell-secreted extracellular vesicles have received great interest as a source of low invasive disease biomarkers because they are found in many body fluids, including urine. The current work describes a pilot study to generate an array-based catalogue of mRNA associated to urinary vesicles, and also a comparison with samples obtained from bladder cancer patients. After an analysis of presence/absence of transcripts in bladder cancer EVs, a list of genes was selected for further validation using PCR technique. We found four genes differentially expressed in cancer samples. LASS2 and GALNT1 were present in cancer patients, while ARHGEF39 and FOXO3 were found only in non-cancer urinary vesicles. Previous studies have pointed to the involvement of those genes in tumour progression and metastasis.

  20. Thyroid diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Scriba, P C; Boerner, W; Emrich, S; Gutekunst, R; Herrmann, J; Horn, K; Klett, M; Krueskemper, H L; Pfannenstiel, P; Pickardt, C R

    1985-03-01

    None of the in-vitro and in-vivo methods listed permits on unambiguous diagnosis when applied alone, owing to the fact that similar or even identical findings are obtained for various individual parameters in different thyroid diseases. Further, especially the in-vitro tests are also subject to extrathyroidal effects which may mask the typical findings. The limited and varying specificity and sensitivity of the tests applied, as well as the falsification of results caused by the patients' idiosyncracies and the methodology, make it necessary to interpret and evaluate the in-vivo and in-vitro findings only if the clinical situation (anamnesis and physical examination) is known. For maximum diagnostic quality of the tests, the initial probability of the assumed type of thyroid disease must be increased (formulation of the clinical problem). The concepts of exclusion diagnosis and identification must be distinguished as well as the diagnosis of functional disturbances on the one hand and of thyroid diseases on the other. Both of this requires a qualified, specific and detailed anamnesis and examination procedure, and the clinical examination remains the obligatory basis of clinical diagnostics. In case of inexplicable discrepancies between the clinical manifestations and the findings obtained with specific methods, or between the findings obtained with a specific method, the patient should be referred to an expert institution, or the expert institution should be consulted.

  1. Thyroid diagnostics

    International Nuclear Information System (INIS)

    Scriba, P.C.; Boerner, W.; Emrich, S.; Gutekunst, R.; Herrmann, J.; Horn, K.; Klett, M.; Krueskemper, H.L.; Pfannenstiel, P.; Pickardt, C.R.; Reiners, C.; Reinwein, D.; Schleusener, H.

    1985-01-01

    None of the in-vitro and in-vivo methods listed permits on unambiguous diagnosis when applied alone, owing to the fact that similar or even identical findings are obtained for various individual parameters in different thyroid diseases. Further, especially the in-vitro tests are also subject to extrathyroidal effects which may mask the typical findings. The limited and varying specificity and sensitivity of the tests applied, as well as the falsification of results caused by the patients' idiosyncracies and the methodology, make it necessary to interpret and evaluate the in-vivo and in-vitro findings only if the clinical situation (anamnesis and physical examination) is known. For maximum diagnostic quality of the tests, the initial probability of the assumed type of thyroid disease must be increased (formulation of the clinical problem). The concepts of exclusion diagnosis and identification must be distinguished as well as the diagnosis of functional disturbances on the one hand and of thyroid diseases on the other. Both of this requires a qualified, specific and detailed anamnesis and examination procedure, and the clinical examination remains the obligatory basis of clinical diagnostics. In case of inexplicable discrepancies between the clinical manifestations and the findings obtained with specific methods, or between the findings obtained with a specific method, the patient should be referred to an expert institution, or the expert institution should be consulted. (orig./MG) [de

  2. Ambient diagnostics

    CERN Document Server

    Cai, Yang

    2014-01-01

    Part I. FundamentalsIntroductionWhat is Ambient Diagnostics?Diagnostic ModelsMultimedia IntelligenceCrowd SourcingSoft SensorsScience of SimplicityPersonal DiagnosesBasic AlgorithmsBasic ToolsSummaryProblemsTransformationEarly Discoveries of Heartbeat PatternsTransforms, Features, and AttributesSequential FeaturesSpatiotemporal FeaturesShape FeaturesImagery FeaturesFrequency Domain FeaturesMulti-Resolution FeaturesSummaryProblemsPattern RecognitionSimilarities and DistancesClustering MethodsClassification MethodsClassifier Accuracy MeasuresSummaryProblemsPart II. Multimedia IntelligenceSound RecognitionMicrophone AppsModern Acoustic Transducers (Microphones)Frequency Response CharacteristicsDigital Audio File FormatsHeart Sound SensingLung Sound SensingSnore MeterSpectrogram (STFT)Ambient Sound AnalysisSound RecognitionRecognizing Asthma SoundPeak ShiftFeature CompressionRegroupingNoise IssuesFuture ApplicationsSummaryProblemsColor SensorsColor SensingHuman Color VisionColor SensorsColor Matching ExperimentsC...

  3. Diagnostic significance of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in thrombolytic treatment for acute myocardial infarction: its potential in assessing reperfusion.

    Science.gov (United States)

    van der Wall, E E; van Dijkman, P R; de Roos, A; Doornbos, J; van der Laarse, A; Manger Cats, V; van Voorthuisen, A E; Matheijssen, N A; Bruschke, A V

    1990-01-01

    The diagnostic value of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in patients treated by thrombolysis for acute myocardial infarction was assessed in 27 consecutive patients who had a first acute myocardial infarction (14 anterior, 13 inferior) and who underwent thrombolytic treatment and coronary arteriography within 4 hours of the onset of symptoms. Magnetic resonance imaging was performed 93 hours (range 15-241) after the onset of symptoms. A Philips Gyroscan (0.5 T) was used, and spin echo measurements (echo time 30 ms) were made before and 20 minutes after intravenous injection of 0.1 mmol/kg gadolinium-DTPA. In all patients contrast enhancement of the infarcted areas was seen after Gd-DTPA. The signal intensities of the infarcted and normal values were used to calculate the intensity ratios. Mean (SD) intensity ratios after Gd-DTPA were significantly increased (1.15 (0.17) v 1.52 (0.29). Intensity ratios were higher in the 17 patients who underwent magnetic resonance imaging more than 72 hours after the onset of symptoms than in the 10 who underwent magnetic resonance imaging earlier, the difference being significantly greater after administration of Gd-DTPA (1.38 (0.12) v 1.61 (0.34). When patients were classified according to the site and size of the infarcted areas, or to reperfusion (n = 19) versus non-reperfusion (n = 8), the intensity ratios both before and after Gd-DTPA did not show significant differences. Magnetic resonance imaging with Gd-DTPA improved the identification of acutely infarcted areas, but with current techniques did not identify patients in whom thrombolytic treatment was successful. Images PMID:2310640

  4. Diagnostic accuracy of organ electrodermal diagnostics | Szopinski ...

    African Journals Online (AJOL)

    Objective. To estimate the diagnostic accuracy as well as the scope of utilisation of a new bio-electronic method of organ diagnostics. Design. Double-blind comparative study of the diagnostic results obtained by means of organ electrodermal diagnostics (OED) and clinical diagnoses, as a criterion standard. Setting.

  5. SNS Diagnostics

    International Nuclear Information System (INIS)

    Shea, T.J.; Cameron, P.; Doolittle, L.; Power, J.

    2000-01-01

    The Spallation Neutron Source (SNS) Project is a collaborative effort to build the next generation neutron science facility at Oak Ridge, TN. The facility will deliver a 2 MW proton beam to a liquid mercury target. Neutrons from this target will be moderated and sent to several state-of-the-art instruments. Six national laboratories are involved in SNS construction. Berkeley (LBNL) will build the front end that produces a 2.5 MeV, 52 mA H-beam. Los Alamos (LANL) is responsible for the 1 GeV linac with a superconducting section provided by Thomas Jefferson (JLab). Brookhaven (BNL) is building the transfer lines and accumulator ring. Oak Ridge (ORNL) and Argonne (ANL) have responsibility for the target and instruments. All activities are coordinated by the SNS project office at Oak Ridge. The high beam power, a desired availability of 95%, and an aggressive commissioning schedule lead to some interesting challenges in beam diagnostics

  6. Recognition of Potentially Novel Human Disease-Associated Pathogens by Implementation of Systematic 16S rRNA Gene Sequencing in the Diagnostic Laboratory▿ †

    Science.gov (United States)

    Keller, Peter M.; Rampini, Silvana K.; Büchler, Andrea C.; Eich, Gerhard; Wanner, Roger M.; Speck, Roberto F.; Böttger, Erik C.; Bloemberg, Guido V.

    2010-01-01

    Clinical isolates that are difficult to identify by conventional means form a valuable source of novel human pathogens. We report on a 5-year study based on systematic 16S rRNA gene sequence analysis. We found 60 previously unknown 16S rRNA sequences corresponding to potentially novel bacterial taxa. For 30 of 60 isolates, clinical relevance was evaluated; 18 of the 30 isolates analyzed were considered to be associated with human disease. PMID:20631113

  7. The potential of circulating extracellular small RNAs (smexRNA) in veterinary diagnostics-Identifying biomarker signatures by multivariate data analysis.

    Science.gov (United States)

    Melanie, Spornraft; Benedikt, Kirchner; Pfaffl, Michael W; Irmgard, Riedmaier

    2015-09-01

    Worldwide growth and performance-enhancing substances are used in cattle husbandry to increase productivity. In certain countries however e.g., in the EU, these practices are forbidden to prevent the consumers from potential health risks of substance residues in food. To maximize economic profit, 'black sheep' among farmers might circumvent the detection methods used in routine controls, which highlights the need for an innovative and reliable detection method. Transcriptomics is a promising new approach in the discovery of veterinary medicine biomarkers and also a missing puzzle piece, as up to date, metabolomics and proteomics are paramount. Due to increased stability and easy sampling, circulating extracellular small RNAs (smexRNAs) in bovine plasma were small RNA-sequenced and their potential to serve as biomarker candidates was evaluated using multivariate data analysis tools. After running the data evaluation pipeline, the proportion of miRNAs (microRNAs) and piRNAs (PIWI-interacting small non-coding RNAs) on the total sequenced reads was calculated. Additionally, top 10 signatures were compared which revealed that the readcount data sets were highly affected by the most abundant miRNA and piRNA profiles. To evaluate the discriminative power of multivariate data analyses to identify animals after veterinary drug application on the basis of smexRNAs, OPLS-DA was performed. In summary, the quality of miRNA models using all mapped reads for both treatment groups (animals treated with steroid hormones or the β-agonist clenbuterol) is predominant to those generated with combined data sets or piRNAs alone. Using multivariate projection methodologies like OPLS-DA have proven the best potential to generate discriminative miRNA models, supported by small RNA-Seq data. Based on the presented comparative OPLS-DA, miRNAs are the favorable smexRNA biomarker candidates in the research field of veterinary drug abuse.

  8. The Alcohol Use Disorders Identification Test and carbohydrate-deficient transferrin in alcohol-related sickness absence.

    Science.gov (United States)

    Hermansson, Ulric; Helander, Anders; Brandt, Lena; Huss, Anders; Rönnberg, Sten

    2002-01-01

    Previous studies have shown that elevated, risky levels of alcohol consumption may lead to higher rates of sickness absence. However, no studies have examined the Alcohol Use Disorders Identification Test (AUDIT) or serum carbohydrate-deficient transferrin (CDT) in relation to sickness absence in the workplace. The purpose of this study was to examine the relationship between sick-days, 12 months before screening, and the AUDIT and CDT (CDTect kit). Serum gamma-glutamyltransferase also was used for comparison. The study was carried out over 36 months in a large workplace and formed part of an ongoing controlled study. In conjunction with a routine health examination, employees were offered the opportunity to undergo an alcohol screening. Absence data were obtained from the company payroll system, and sickness absence was analyzed by using a three-ordinal level cumulative logistic model on the number of sick-days. Odds ratios (OR) and 95% confidence intervals (CI) are reported. Of the 989 subjects who participated in the study, 193 (19.5%) screened positive in relation to either the AUDIT (>or=8 points) or CDT (women), or both. Employees who screened positive with the AUDIT had a significantly higher proportion of sick-days (p = 0.047) compared with those who screened negative (OR = 1.4, CI 1.0-1.9). Neither long, continuous periods of sickness absence nor absence on Mondays or Fridays gave a clear indication of individuals who screened positive on the AUDIT or CDT test. Our data indicate that individuals with moderately elevated or risky levels of alcohol consumption show an increase in sick-days. Accordingly, workplaces have a good reason for using a more systematic approach to alcohol screening in routine workplace health examinations.

  9. [The clinical significance of the measurement of plasma transferrin as a growth factor. II. The changes in various endocrine status].

    Science.gov (United States)

    Matsubara, M; Odagaki, E; Morioka, T; Nakagawa, K

    1987-05-20

    The clinical significance of the measurement of plasma transferrin (Tf) in patients with hypophysial disorders was reported in our previous papers. In the present study, we determined plasma Tf levels in 55 patients with various endocrine states and considered their clinical significance compared with plasma somatomedin-C (SM-C) levels. Plasma Tf levels decreased significantly in patients with anorexia nervosa (p less than 0.02), hyperthyroidism (p less than 0.05), primary hypothyroidism (p less than 0.05) and Cushing's syndrome (p less than 0.05), while they were elevated significantly in pregnancy (p less than 0.01) or females using estrogens (p less than 0.05). The former two declines were considered a reflection of the malnutritional state of the patients since a significant negative correlation was observed between plasma Tf levels and the percentile deficit from the ideal body weight in patients with anorexia nervosa (p less than 0.01), or between plasma Tf levels and elevated T3 levels which induce hypermetabolism in patients with hyperthyroidism (p less than 0.01). A significant correlation was observed between the SM-C and Tf levels in these subjects (including normal controls and patients with hypophysial disorders) as a whole (r = 0.79, p less than 0.001). These data indicate that plasma Tf is changeable according to the endocrinological and nutritional conditions with good correlation to the SM-C, and it is suggested that Tf also operates as a growth factor in vivo.

  10. Intracellular targeting of mercaptoundecahydrododecaborate (BSH) to malignant glioma by transferrin-PEG liposomes for boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    Doi, Atsushi; Miyatake, Shin-ichi; Iida, Kyouko

    2006-01-01

    Malignant glioma is one of the most difficult tumor to control with usual therapies. In our institute, we select boron neutron capture therapy (BNCT) as an adjuvant radiation therapy after surgical resection. This therapy requires the selective delivery of high concentration of 10 B to malignant tumor tissue. In this study, we focused on a tumor-targeting 10 B delivery system (BDS) for BNCT that uses transferrin-conjugated polyethylene-glycol liposome encapsulating BSH (TF-PEG liposome-BSH) and compared 10 B uptake of the tumor among BSH, PEG liposome-BSH and TF-PEG liposome-BSH. In vitro, we analyzed 10 B concentration of the cultured human U87Δ glioma cells incubated in medium containing 20 μg 10 B/ml derived from each BDS by inductively coupled plasma atomic emission spectrometry (ICP-AES). In vivo, human U87Δ glioma-bearing nude mice were administered with each BDS (35mg 10 B/kg) intravenously. We analyzed 10 B concentration of tumor, normal brain and blood by ICP-AES. The TF-PEG liposome-BSH showed higher absolute concentration more than the other BDS. Moreover, TF-PEG liposome-BSH decreased 10 B concentration in blood and normal tissue while it maintained high 10 B concentration in tumor tissue for a couple of days. This showed the TF-PEG liposome-BSH caused the selective delivery of high concentration of 10 B to malignant tumor tissue. The TF-PEG liposome-BSH is more potent BDS for BNCT to obtain absolute high 10 B concentration and good contrast between tumor and normal tissue than BSH and PEG liposome-BSH. (author)

  11. Iron regulation of hepcidin despite attenuated Smad1,5,8 signaling in mice without transferrin receptor 2 or Hfe

    Science.gov (United States)

    Corradini, Elena; Rozier, Molly; Meynard, Delphine; Odhiambo, Adam; Lin, Herbert Y.; Feng, Qi; Migas, Mary C.; Britton, Robert S.; Babitt, Jodie L.; Fleming, Robert E.

    2011-01-01

    Background & Aims HFE and transferrin receptor 2 (TFR2) are each necessary for the normal relationship between body iron status and liver hepcidin expression. In murine Hfe and Tfr2 knockout models of hereditary hemochromatosis (HH), signal transduction to hepcidin via the bone morphogenetic protein 6 (Bmp6)/Smad1,5,8 pathway is attenuated. We examined the effect of dietary iron on regulation of hepcidin expression via the Bmp6/Smad1,5,8 pathway using mice with targeted disruption of Tfr2, Hfe, or both genes. Methods Hepatic iron concentrations and mRNA expression of Bmp6 and hepcidin were compared with wild-type mice in each of the HH models on standard or iron-loading diets. Liver phospho-Smad (P-Smad)1,5,8 and Id1 mRNA levels were measured as markers of Bmp/Smad signaling. Results While Bmp6 expression was increased, liver hepcidin and Id1 expression were decreased in each of the HH models compared with wild-type mice. Each of the HH models also demonstrated attenuated P-Smad1,5,8 levels relative to liver iron status. Mice with combined Hfe/Tfr2 disruption were most affected. Dietary iron loading increased hepcidin and Id1 expression in each of the HH models. Compared with wild-type mice, HH mice demonstrated attenuated (Hfe knockout) or no increases in P-Smad1,5,8 levels in response to dietary iron loading. Conclusions These observations demonstrate that Tfr2 and Hfe are each required for normal signaling of iron status to hepcidin via Bmp6/Smad1,5,8 pathway. Mice with combined loss of Hfe and Tfr2 up-regulate hepcidin in response to dietary iron loading without increases in liver BMP6 mRNA or steady-state P-Smad1,5,8 levels. PMID:21745449

  12. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

    Science.gov (United States)

    Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

    2011-11-01

    Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Copyright © 2011 Wiley-Liss, Inc.

  13. Diagnostic thoracoscopy

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2002-01-01

    Full Text Available Diagnostic thoracoscopy in patients with pleural effusion of unclear origin mostly provides the correct diagnosis. Results from published reports of previous researches are not uniform. In 47 male and 20 female patients with pleural effusion of unknown etiology, after receiving negative results obtained from cytological finding of pleural effusion and percutaneous needle biopsy, thoracoscopy with biopsy of one or both pleurae was performed. Procedure was done in local anesthesia using Stortz rigid thoracoscope. In 37 patients with malignant disease (primary or metastatic diagnosis was confirmed histopathologically in 31 patient (81.12%. In 27 patients with inflammatory pleural disease diagnosis was confirmed histopathologically in 22 patients (81.4%. Among 11 patients with specific pleural effusions, tuberculosis was confirmed in 10 (90.91%. Normal finding in cases of spontaneous pneumothorax and pulmonary embolism was taken as a positive result. Total number of positive findings was 55 (82.10%. In one patient, the third spontaneous pneumothorax was the indication for thoracoscopy, and after numerous bullae were seen during the procedure, talcum powder pleurodesis was done. In four patients low intensity subcutaneous emphysema occurred one day after thoracoscopy. It can be concluded that thoracoscopy in local anesthesia out of the operating room is good and practical method for solving the unclear pleural effusions, with neglectable rate of complications.

  14. Mitigation diagnostics

    International Nuclear Information System (INIS)

    Hall, S.T.

    1990-01-01

    This paper reports that experience in the remediation of schools and other large buildings has shown the importance of the effects of both the location of geologic sources and HVAC-induced distribution of indoor radon. In general, elevated radon in areas of schools with evenly distributed HVAC pressures are correlated with maximum soil radon emanations. However, strong or unequal HVAC effects can redistribute indoor radon to areas away from the direct source. Effective remediation required a complete understanding of both contributions. In some schools, highest indoor radon levels were located near large return ducts and were attributed to proximity to negative HVAC pressure. Successful sub-slab depressurization systems were installed, however, in rooms with lower indoor but greatest sub-slab radon levels, closest to the source. This shows the inadequacy of using indoor radon levels alone as a basis for remediation. Wings of two other schools with radon problems have equivalent window fan coil units in rooms of equal size and no central HVAC system. Highest indoor radon levels correlated well with highest sub-slab radon levels due to the equivalent effects of the window units. Diagnostic tests in other schools have revealed: blockwall radon transport to upper floors; high blockwall radon adjacent to sub-slab sources; and elevated indoor radon over crawlspace being drawn upward by HVAC-induced negative pressure, determined from indoor to outdoor micromanometer measurements

  15. Executive functions as a potential neurocognitive endophenotype in anxiety disorders: A systematic review considering DSM-IV and DSM-5 diagnostic criteria classification

    Directory of Open Access Journals (Sweden)

    Juliana de Lima Muller

    Full Text Available Evidence in the literature indicates that neurocognitive impairments may represent endophenotypes in psychiatric disorders.Objective:This study aimed to conduct a systematic review on executive functions as a potential neurocognitive endophenotype in anxiety disorder diagnosis according to the DSM-IV and DSM-5 classifications.Methods:A literature search of the LILACS, Cochrane Library, Index Psi Periódicos Técnico-Científicos, PubMed and PsycInfo databases was conducted, with no time limits. Of the 259 studies found, 14 were included in this review.Results:Only studies on obsessive-compulsive disorder (OCD were found. The executive function components of decision-making, planning, response inhibition, behavioral reversal/alternation, reversal learning and set-shifting/cognitive flexibility were considered to be a neurocognitive endophenotypes in OCD.Conclusion:Further studies on executive functions as a neurocognitive endophenotype in other anxiety disorders are needed since these may have different neurocognitive endophenotypes and require other prevention and treatment approaches.

  16. Elevated temperature inhibits recruitment of transferrin-positive vesicles and induces iron-deficiency genes expression in Aiptasia pulchella host-harbored Symbiodinium.

    Science.gov (United States)

    Song, Po-Ching; Wu, Tsung-Meng; Hong, Ming-Chang; Chen, Ming-Chyuan

    2015-10-01

    Coral bleaching is the consequence of disruption of the mutualistic Cnidaria-dinoflagellate association. Elevated seawater temperatures have been proposed as the most likely cause of coral bleaching whose severity is enhanced by a limitation in the bioavailability of iron. Iron is required by numerous organisms including the zooxanthellae residing inside the symbiosome of cnidarian cells. However, the knowledge of how symbiotic zooxanthellae obtain iron from the host cells and how elevated water temperature affects the association is very limited. Since cellular iron acquisition is known to be mediated through transferrin receptor-mediated endocytosis, a vesicular trafficking pathway specifically regulated by Rab4 and Rab5, we set out to examine the roles of these key proteins in the iron acquisition by the symbiotic Symbiodinium. Thus, we hypothesized that the iron recruitments into symbiotic zooxanthellae-housed symbiosomes may be dependent on rab4/rab5-mediated fusion with vesicles containing iron-bound transferrins and will be retarded under elevated temperature. In this study, we cloned a novel monolobal transferrin (ApTF) gene from the tropical sea anemone Aiptasia pulchella and confirmed that the association of ApTF with A. pulchella Rab4 (ApRab4) or A. pulchella Rab5 (ApRab5) vesicles is inhibited by elevated temperature through immunofluorescence analysis. We confirmed the iron-deficient phenomenon by demonstrating the induced overexpression of iron-deficiency-responsive genes, flavodoxin and high-affinity iron permease 1, and reduced intracellular iron concentration in zooxanthellae under desferrioxamine B (iron chelator) and high temperature treatment. In conclusion, our data are consistent with algal iron deficiency being a contributing factor for the thermal stress-induced bleaching of symbiotic cnidarians. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Total and cause-specific mortality by elevated transferrin saturation and hemochromatosis genotype in individuals with diabetes - two general population studies

    DEFF Research Database (Denmark)

    Ellervik, Christina; Mandrup-Poulsen, Thomas; Tybjærg-Hansen, Anne

    2013-01-01

    ObjectiveMortality is increased in patients with hereditary hemochromatosis, in individuals from the general population with increased transferrin saturation(TS), and also in patients with diabetes type 1 and increased TS from a highly specialised diabetes clinic. Thus, we have recommended targeted...... and hemochromatosis genotype(HFE) C282Y/C282Y in individuals with diabetes(type 1,N=118;type 2,N=3228;total,N=3346).ResultsThe cumulative survival was reduced in individuals with diabetes with TS≥50% vs....

  18. Lectures in plasma diagnostics

    International Nuclear Information System (INIS)

    Hutchinson, I.H.

    1990-06-01

    This paper discusses the following topics on plasma diagnostics: Electric probes in flowing and magnetized plasmas; Electron cyclotron emission absorption; Magnetic diagnostics; Spectroscopy; and Thomson Scattering

  19. Diagnosis of protein-losing gastroenteropathy by sup 111 In-transferrin scanning and fecal excretion test

    Energy Technology Data Exchange (ETDEWEB)

    Urita, Yoshihisa (Toho Univ., Tokyo (Japan). School of Medicine)

    1991-10-01

    A total of 12 patients with gastroenteropathy were studied for possible protein loss. The underlying diseases were intestinal lymphangiectasia, ulcerative colitis and Crohn's disease in 2 patients each and Menetrier's disease, Cronkhite-Canada syndrome, postgastrectomy syndrome, severe atrophic gastritis, gastric cancer and gastroenteropathy of unknown origin in one patient each. The controls were four healthy volunteers and 9 patients with benign disease not accompanied by lesions in the digestive tract and protein loss {sup 111}In-transferrin Tf was prepared by incubating 2-3 mCi of {sup 111}In-chloride with 15-20 ml of each patient's plasma in a sterilized vial at room temperature for 1 hour. After iv injection of {sup 111}In-Tf the patients were scanned at given intervals of time for 72 hours to localize protein loss. Seventy-two hour fecal {sup 111}In-Tf excretion was also measured. {sup 111}In-Tf was detected in the feces of all patients. The recovery rate in the patient group was 7.95{+-}3.65%, being significantly higher than 0.48{+-}0.26% in the control group. However {sup 111}In-Tf scanning showed the site of protein loss only in 6 patients. Negative scan in six other patients was thought to be associated with extensive inflammation and severe diarrhea. Five of the 12 patients were observed before and after treatment. A decrease in fecal {sup 111}In-Tf excretion with clinical improvement was noted in the 5 patients after treatment. The site of protein loss could be demonstrated in 3 of the 5 patients before treatment. Its site in 1 of the 3 patients was the small intestine. However accumulation of {sup 111}In-Tf was found there in the 3 patients after treatment. The site of protein loss in 1 of 3 patients was the small intestine. {sup 111}In-Tf scanning is particularly useful when the small intestine is involved, because surgery is contraindicated in this case. Fecal {sup 111}In-Tf excretion test is mandatory when the site of protein loss

  20. Diagnostic potential of PET/CT using a {sup 68}Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Sawicki, Lino M.; Buchbender, Christian; Boos, Johannes; Antoch, Gerald [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Dusseldorf (Germany); Giessing, Markus [University Dusseldorf, Medical Faculty, Department of Urology, Dusseldorf (Germany); Ermert, Johannes [Juelich Research Center, Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Juelich (Germany); Antke, Christina; Hautzel, Hubertus [University Dusseldorf, Medical Faculty, Department of Nuclear Medicine, Dusseldorf (Germany)

    2017-01-15

    To evaluate the diagnostic potential of whole-body PET/CT using a {sup 68}Ga-labelled PSMA ligand in renal cell carcinoma (RCC). Six patients with histopathologically proven RCC underwent {sup 68}Ga-PSMA PET/CT. Each PET/CT scan was evaluated in relation to lesion count, location and dignity. SUVmax was measured in primary tumours and PET-positive metastases. Tumour-to-background SUVmax ratios (TBR{sub SUVmax}) were calculated for primary RCCs in relation to the surrounding normal renal parenchyma. Metastasis-to-background SUVmax ratios (MBR{sub SUVmax}) were calculated for PET-positive metastases in relation to gluteal muscle. Five primary RCCs and 16 metastases were evaluated. The mean SUVmax of the primary RCCs was 9.9 ± 9.2 (range 1.7 - 27.2). Due to high uptake in the surrounding renal parenchyma, the mean TBR{sub SUVmax} of the primary RCCs was only 0.2 ± 0.3 (range 0.02 - 0.7). Eight metastases showed focal {sup 68}Ga-PSMA uptake (SUVmax 9.9 ± 8.3, range 3.4 - 25.6). The mean MBR{sub SUVmax} of these PET-positive metastases was 11.7 ± 0.2 (range 4.4 - 28.1). All PET-negative metastases were subcentimetre lung metastases. {sup 68}Ga-PSMA PET/CT appears to be a promising method for detecting RCC metastases. However, no additional diagnostic value in assessing the primary tumour was found. (orig.)

  1. TIBC, UIBC and Transferrin

    Science.gov (United States)

    ... circulating and stored iron may eventually lead to iron deficiency anemia (decreased hemoglobin and hematocrit , smaller and paler red ... results of each can help identify iron deficiency, iron deficiency anemia, or too much iron in the body (overload). ...

  2. Expression of the amino-terminal half-molecule of human serum transferrin in cultured cells and characterization of the recombinant protein

    International Nuclear Information System (INIS)

    Funk, W.D.; MacGillivray, R.T.A.; Mason, A.B.; Brown, S.A.; Woodworth, R.C.

    1990-01-01

    A human liver cDNA library was screened with a synthetic oligonucleotide, complementary to the 5' region of human transferrin mRNA, as a hybridization probe. The full-length human cDNA clone isolated from this screen contained part of the 5' untranslated region, the complete coding region for the signal peptide and the two lobes of transferrin, the 3' untranslated region, and a poly(A) tail. By use of oligonucleotide-directed mutagenesis in vitro, two translational stop codons and a HindIII site were introduced after the codon for Asp-337. This fragment was inserted into two different expression vectors that were then introduced into Escherichia coli. As judged by NaDodSO 4 -polyacrylamide gel electrophoresis and Western blot analysis, however, recombinant hTF/2N was undetectable in bacteria transformed by these plasmids. Concurrently, the authors developed a plasmid vector for the expression of recombinant hTF/2N in eukaryotic cells. The recombinant hTF/2N appeared to behave identically with the proteolytically derived half-molecule, but to show a higher degree of monodispersity than the latter protein. Addition of m-fluorotyrosine to the culture medium resulted in random incorporation of this amino acid into cellular protein in lieu of tyrosine. Purified recombinant 19 F-Tyr hTF/2N gave four well-resolved 19 F NMR resonances of 20-40 Hz line width, two with suggestions of shoulders

  3. Fabrication of transferrin functionalized gold nanoclusters/graphene oxide nanocomposite for turn-on near-infrared fluorescent bioimaging of cancer cells and small animals.

    Science.gov (United States)

    Wang, Yong; Chen, Jia-Tong; Yan, Xiu-Ping

    2013-02-19

    Transferrin (Tf)-functionalized gold nanoclusters (Tf-AuNCs)/graphene oxide (GO) nanocomposite (Tf-AuNCs/GO) was fabricated as a turn-on near-infrared (NIR) fluorescent probe for bioimaging cancer cells and small animals. A one-step approach was developed to prepare Tf-AuNCs via a biomineralization process with Tf as the template. Tf acted not only as a stabilizer and a reducer but also as a functional ligand for targeting the transferrin receptor (TfR). The prepared Tf-AuNCs gave intense NIR fluorescence that can avoid interference from biological media such as tissue autofluorescence and scattering light. The assembly of Tf-AuNCs and GO gave the Tf-AuNCs/GO nanocomposite, a turn-on NIR fluorescent probe with negligible background fluorescence due to the super fluorescence quenching property of GO. The NIR fluorescence of the Tf-AuNCs/GO nanocomposite was effectively restored in the presence of TfR, due to the specific interaction between Tf and TfR and the competition of TfR with the GO for the Tf in Tf-AuNCs/GO composite. The developed turn-on NIR fluorescence probe offered excellent water solubility, stability, and biocompatibility, and exhibited high specificity to TfR with negligible cytotoxicity. The probe was successfully applied for turn-on fluorescent bioimaging of cancer cells and small animals.

  4. Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer

    International Nuclear Information System (INIS)

    Nagai, Kentaro; Nakahata, Shingo; Shimosaki, Shunsuke; Tamura, Tomohiro; Kondo, Yuudai; Baba, Takashi; Taki, Tomohiko; Taniwaki, Masafumi; Kurosawa, Gene; Sudo, Yukio; Okada, Seiji; Sakoda, Sumio; Morishita, Kazuhiro

    2014-01-01

    Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up to 20% of oral dysplasia cases have been suggested to undergo malignant transformation to OSCC; however, there are no methods to predict OSCC development. In this study, to identify the genes associated with oral dysplasia progression, we performed genomic copy number analyses of genomic DNA samples isolated from primary oral dysplasia and OSCC via the microdissection method and found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was significantly higher than that in dysplasia, suggesting that OSCC disease progression might be related to TFRC expression. Additionally, we investigated the in vitro and in vivo impacts of a newly established anti-human TFRC monoclonal antibody, which was isolated from a human cDNA library using the phage-display method, on cell proliferation and survival. The anti-TFRC antibody blocked the interaction between transferrin and TFRC and consequently inhibited iron uptake, leading to the iron deprivation-mediated suppression of cell growth and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore, we suggest our developed complete human anti-human TFRC antibody as a useful, novel treatment for oral dysplasia and OSCC

  5. SMALL CRATERS AND THEIR DIAGNOSTIC POTENTIAL

    Directory of Open Access Journals (Sweden)

    R. Bugiolacchi

    2017-07-01

    Full Text Available I analysed and compared the size-frequency distributions of craters in the Apollo 17 landing region, comprising of six mare terrains with varying morphologies and cratering characteristics, along with three other regions allegedly affected by the same secondary event (Tycho secondary surge. I propose that for the smaller crater sizes (in this work 9–30 m, a] an exponential curve of power −0.18D can approximate Nkm−2 crater densities in a regime of equilibrium, while b] a power function D−3 closely describes the factorised representation of craters by size (1 m. The saturation level within the Central Area suggests that c] either the modelled rates of crater erosion on the Moon should be revised, or that the Tycho event occurred much earlier in time than the current estimate. We propose that d] the size-frequency distribution of small secondary craters may bear the signature (in terms of size-frequency distribution of debris/surge of the source impact and that this observation should be tested further.

  6. Gliomatosis cerebri: The diagnostic potential of MRI

    International Nuclear Information System (INIS)

    Rodiek, S.O.; Hufnagl, J.M.; Staedtisches Krankenhaus Muenchen-Bogenhausen

    1991-01-01

    Gliomatosis cerebri is a rare tumor of neuroepithelial origin in middle aged persons. MRI predominantly shows a bilateral and diffuse infiltration of midline adjacent brain structures including medulla. Areas with focal anaplasia occasionally reveal an accumulation of contrast media. The diffuse tumor manifestation requires a differentiation from encephalitis and demyelinating diseases with a similar distribution pattern of lesions. Three cases have been examined. In conclusion the performance of MRI including control and brain biopsy are indicated to establish an in vivo diagnosis. (orig./GDG) [de

  7. Diagnostic radiation of potentially reproductive females

    Energy Technology Data Exchange (ETDEWEB)

    Abd El-Bagi, M E; Al-Mutairi, M S; Al-Thagafi, M A; Al-Masri, N M; Al-Sasi, O [Department of Radiology and Imaging, Armed Forces Hospital, Riyadh (Saudi Arabia)

    2001-03-01

    Objectives: To find out how consistent or variable is the understanding and practice of radiation protection procedures for women of childbearing age at a multispecialty tertiary hospital. Setting: Riyadh Military Hospital Study. Design: Non-clustered population survey. Methods: A questionnaire was distributed during grand rounds, mid-day clinics and a radiology conference. Questions included which radiation protection rule does the respondent use for females, whether he or she is familiar with those rules and what is his or her source of reference. Further questions were about the radiation dangers to the fetus. Results: Response was 95 (100%). Fifty-seven (60%) were males and 38 (40%) were females. The majority 50 (53%) were Saudis, 16 (17%) Western and 29 (30%) were other nationals. Sixty-two (65%) followed the old rule '10-day rule'; 17 (18%) followed the new '28-day rule' and 16 (17%) didn't know which rule to follow. None of those who followed the '28-day rule' indicated hospital policy as their reference. Conclusions: The understanding and practice of radiation protection guidelines for females is inconsistent. There is significant unfamiliarity with the radiation protection rules among our hospital practitioners. (author)

  8. Diagnostic radiation of potentially reproductive females

    International Nuclear Information System (INIS)

    Abd El-Bagi, M.E.; Al-Mutairi, M.S.; Al-Thagafi, M.A.; Al-Masri, N.M.; Al-Sasi, O.

    2001-01-01

    Objectives: To find out how consistent or variable is the understanding and practice of radiation protection procedures for women of childbearing age at a multispecialty tertiary hospital. Setting: Riyadh Military Hospital Study. Design: Non-clustered population survey. Methods: A questionnaire was distributed during grand rounds, mid-day clinics and a radiology conference. Questions included which radiation protection rule does the respondent use for females, whether he or she is familiar with those rules and what is his or her source of reference. Further questions were about the radiation dangers to the fetus. Results: Response was 95 (100%). Fifty-seven (60%) were males and 38 (40%) were females. The majority 50 (53%) were Saudis, 16 (17%) Western and 29 (30%) were other nationals. Sixty-two (65%) followed the old rule '10-day rule'; 17 (18%) followed the new '28-day rule' and 16 (17%) didn't know which rule to follow. None of those who followed the '28-day rule' indicated hospital policy as their reference. Conclusions: The understanding and practice of radiation protection guidelines for females is inconsistent. There is significant unfamiliarity with the radiation protection rules among our hospital practitioners. (author)

  9. Diagnostic criteria in MR neurography

    International Nuclear Information System (INIS)

    Baeumer, P.

    2017-01-01

    Peripheral neuropathies are frequent and can mostly be correctly diagnosed by clinical examination and electrophysiology; however, diagnostically difficult cases are sometimes encountered especially with respect to precise localization of nerve lesions. Imaging of the peripheral nervous system has been shown to provide additional useful diagnostic information. In addition to the more widely available nerve sonography, magnetic resonance neurography (MRN) is the method of choice in diagnostically complex cases. The most important pulse sequence is a T2-weighted fat-saturated pulse sequence with high in-plane resolution and detects increased T2-weighted signals of nerve fascicles as a highly sensitive sign for nerve lesions. Further established diagnostic criteria are nerve caliber and, less commonly used, contrast agent uptake. The spatial pattern of nerve lesions aids in the diagnostic classification of neuropathies. Functional imaging techniques, such as diffusion tensor imaging (DTI) and nerve perfusion are currently under examination with respect to the clinical potential. If all other diagnostic methods, including clinical examination, electrophysiology and nerve sonography do not arrive at an unambiguous diagnosis of a peripheral neuropathy, MRN should be used. The special value of MRN is demonstrated particularly in complex nerve lesions, such as traumatic plexopathies and in partial fascicular neuropathies and many other indications. (orig.) [de

  10. Diagnostic reasoning strategies and diagnostic success.

    Science.gov (United States)

    Coderre, S; Mandin, H; Harasym, P H; Fick, G H

    2003-08-01

    Cognitive psychology research supports the notion that experts use mental frameworks or "schemes", both to organize knowledge in memory and to solve clinical problems. The central purpose of this study was to determine the relationship between problem-solving strategies and the likelihood of diagnostic success. Think-aloud protocols were collected to determine the diagnostic reasoning used by experts and non-experts when attempting to diagnose clinical presentations in gastroenterology. Using logistic regression analysis, the study found that there is a relationship between diagnostic reasoning strategy and the likelihood of diagnostic success. Compared to hypothetico-deductive reasoning, the odds of diagnostic success were significantly greater when subjects used the diagnostic strategies of pattern recognition and scheme-inductive reasoning. Two other factors emerged as independent determinants of diagnostic success: expertise and clinical presentation. Not surprisingly, experts outperformed novices, while the content area of the clinical cases in each of the four clinical presentations demonstrated varying degrees of difficulty and thus diagnostic success. These findings have significant implications for medical educators. It supports the introduction of "schemes" as a means of enhancing memory organization and improving diagnostic success.

  11. Diagnostics in Japan's microgravity experiments

    Science.gov (United States)

    Kadota, Toshikazu

    1995-01-01

    The achievement of the combustion research under microgravity depends substantially on the availability of diagnostic systems. The non-intrusive diagnostic systems are potentially applicable for providing the accurate, realistic and detailed information on momentum, mass and energy transport, complex gas phase chemistry, and phase change in the combustion field under microgravity. The non-intrusive nature of optical instruments is essential to the measurement of combustion process under microgravity which is very nervous to any perturbation. However, the implementation of the non-intrusive combustion diagnostic systems under microgravity is accompanied by several constraints. Usually, a very limited space is only available for constructing a highly sophisticated system which is so sensitive that it is easily affected by the magnitude of the gravitational force, vibration and heterogeneous field of temperature and density of the environments. The system should be properly adjusted prior to the experiment. Generally, it is quite difficult to tune the instruments during measurements. The programmed sequence of operation should also be provided. Extensive effort has been toward the development of non-intrusive diagnostic systems available for the combustion experiments under microgravity. This paper aims to describe the current art and the future strategy on the non-intrusive diagnostic systems potentially applicable to the combustion experiments under microgravity in Japan.

  12. Procedures in diagnostic radiology

    International Nuclear Information System (INIS)

    Doyle, T.; Hare, W.S.C.; Thomson, K.; Tess, B.

    1989-01-01

    This book outlines the various procedures necessary for the successful practice of diagnostic radiology. Topics covered are: general principles, imaging of the urinary and gastrointestinal tracts, vascular radiology, arthrography, and miscellaneous diagnostic radiologic procedures

  13. Diagnostic Algorithm Benchmarking

    Science.gov (United States)

    Poll, Scott

    2011-01-01

    A poster for the NASA Aviation Safety Program Annual Technical Meeting. It describes empirical benchmarking on diagnostic algorithms using data from the ADAPT Electrical Power System testbed and a diagnostic software framework.

  14. Ares I-X Ground Diagnostic Prototype

    Data.gov (United States)

    National Aeronautics and Space Administration — The automation of pre-launch diagnostics for launch vehicles offers three potential benefits: improving safety, reducing cost, and reducing launch delays. The Ares...

  15. Identification of Tumor Antigen AF20 as Glycosylated Transferrin Receptor 1 in Complex with Heat Shock Protein 90 and/or Transporting ATPase.

    Directory of Open Access Journals (Sweden)

    Jason M Shapiro

    Full Text Available We previously isolated AF20, a murine monoclonal antibody that recognizes a cell surface glycoprotein of approximately 90-110 kDa. The AF20 antigen is specifically expressed in human hepatoma and colon cancer cell lines, and thus could serve as a cancer biomarker. To uncover the molecular identity of the AF20 antigen, a combination of ion-exchange chromatography, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis was employed to purify the AF20 antigen followed by trypsin digestion and mass spectrometry. Surprisingly, three host proteins were thus purified from human hepatoma and colon cancer cell lines: transferrin receptor 1 (TFR1, heat shock protein 90 (HSP90, and Na+/K+ ATPase or Mg++ ATPase. Co-immunoprecipitation followed by Western blot analysis confirmed interaction among the three proteins. However, only the cDNA encoding TFR1 conferred strong cell surface staining by the AF20 antibody following its transient transfection into a cell line lacking endogenous AF20. In support of the molecular identity of AF20 as TFR1, diferric but not iron-free transferrin could prevent AF20 antigen-antibody interaction during immunoprecipitation. Moreover, very similar patterns of AF20 and TFR1 overexpression was documented in colon cancer tissues. In conclusion, AF20 is glycosylated TFR1. This finding could explain the molecular structure of AF20, its cell surface localization, as well as overexpression in cancer cells. Glycosylated TFR1 should serve as a usefulness target for anti-cancer therapy, or a vehicle for delivery of anti-tumor drugs with high affinity and specificity. The biological significance of the complex formation between TFR1, HSP90, and/or transporting ATPase warrants further investigation.

  16. Cross-sectional study of expression of divalent metal transporter-1, transferrin, and hepcidin in blood of smelters who are occupationally exposed to manganese

    Directory of Open Access Journals (Sweden)

    Qiyuan Fan

    2016-09-01

    Full Text Available Background Manganese (Mn is widely used in industries including the manufacture of Mn-iron (Fe alloy. Occupational Mn overexposure causes manganism. Mn is known to affect Fe metabolism; this study was designed to test the hypothesis that workers exposed to Mn may have an altered expression of mRNAs encoding proteins in Fe metabolism. Methods Workers occupationally exposed to Mn (n = 71 from a Mn–Fe alloy factory and control workers without Mn-exposure (n = 48 from a pig-iron plant from Zunyi, China, were recruited for this study. Blood samples were collected into Trizol-containing tubes. Total RNA was isolated, purified, and subjected to real-time RT-PCR analysis. Metal concentrations were quantified by atomic absorption spectrophotometry. Results Working environment and genetic background of both groups were similar except for marked differences in airborne Mn concentrations (0.18 mg/m3 in Mn–Fe alloy factory vs. 0.0022 mg/m3 in pig-Fe plant, and in blood Mn levels (34.3 µg/L vs. 10.4 µg/L. Mn exposure caused a significant decrease in the expression of divalent metal transporter-1 (DMT1, transferrin (Tf and hepcidin by 58.2%, 68.5% and 61.5%, respectively, as compared to controls, while the expression of transferrin receptor (TfR was unaltered. Linear regression analysis revealed that expressions of DMT1, Tf and hepcidin were inversely correlated with the accumulative Mn exposure; the correlation coefficients (r are −0.47, −0.54, and −0.49, respectively (p < 0.01. Conclusion The data suggest that occupational Mn exposure causes decreased expressions of DMT1, Tf and hepcidin in blood cells; the finding will help understand the mechanism underlying Mn exposure-associated alteration in Fe homeostasis among workers.

  17. Enhanced transferrin receptor expression by proinflammatory cytokines in enterocytes as a means for local delivery of drugs to inflamed gut mucosa.

    Directory of Open Access Journals (Sweden)

    Efrat Harel

    Full Text Available Therapeutic intervention in inflammatory bowel diseases (IBDs is often associated with adverse effects related to drug distribution into non-diseased tissues, a situation which attracts a rational design of a targeted treatment confined to the inflamed mucosa. Upon activation of immune cells, transferrin receptor (TfR expression increases at their surface. Because TfR is expressed in all cell types we hypothesized that its cell surface levels are regulated also in enterocytes. We, therefore, compared TfR expression in healthy and inflamed human colonic mucosa, as well as healthy and inflamed colonic mucosa of the DNBS-induced rat model. TfR expression was elevated in the colonic mucosa of IBD patients in both the basolateral and apical membranes of the enterocytes. Increased TfR expression was also observed in colonocytes of the induced colitis rats. To explore the underlying mechanism CaCo-2 cells were treated with various proinflammatory cytokines, which increased both TfR expression and transferrin cellular uptake in a mechanism that did not involve hyper proliferation. These findings were then exploited for the design of targetable carrier towards inflamed regions of the colon. Anti-TfR antibodies were conjugated to nano-liposomes. As expected, iron-starved Caco-2 cells internalized anti-TfR immunoliposomes better than controls. Ex vivo binding studies to inflamed mucosa showed that the anti-TfR immunoliposomes accumulated significantly better in the mucosa of DNBS-induced rats than the accumulation of non-specific immunoliposomes. It is concluded that targeting mucosal inflammation can be accomplished by nano-liposomes decorated with anti-TfR due to inflammation-dependent, apical, elevated expression of the receptor.

  18. Assessing the Association between Serum Ferritin, Transferrin Saturation, and C-Reactive Protein in Northern Territory Indigenous Australian Patients with High Serum Ferritin on Maintenance Haemodialysis

    Directory of Open Access Journals (Sweden)

    Sandawana William Majoni

    2017-01-01

    Full Text Available Objective. To determine the significance of high serum ferritin observed in Indigenous Australian patients on maintenance haemodialysis in the Northern Territory, we assessed the relationship between ferritin and transferrin saturation (TSAT as measures of iron status and ferritin and C-reactive protein (CRP as markers of inflammation. Methods. We performed a retrospective cohort analysis of data from adult patients (≥18 years on maintenance haemodialysis (>3 months from 2004 to 2011. Results. There were 1568 patients. The mean age was 53.9 (11.9 years. 1244 (79.3% were Indigenous. 44.2% (n=693 were male. Indigenous patients were younger (mean age [52.3 (11.1 versus 57.4 (15.2, p<0.001] and had higher CRP [14.7 mg/l (7–35 versus 5.9 mg/l (1.9–17.5, p<0.001], higher median serum ferritin [1069 µg/l (668–1522 versus 794.9 µg/l (558.5–1252.0, p<0.001], but similar transferrin saturation [26% (19–37 versus 28% (20–38, p=0.516]. We observed a small positive correlation between ferritin and TSAT (r2=0.11, p<0.001, no correlation between ferritin and CRP (r2 = 0.001, p<0.001, and positive association between high serum ferritin and TSAT (p<0.001, Indigenous ethnicity (p<0.001, urea reduction ratio (p=0.001, and gender (p<0.001 after adjustment in mixed regression analysis. Conclusion. Serum ferritin and TSAT may inadequately reflect iron status in this population. The high ferritin was poorly explained by inflammation.

  19. Use of finger-prick dried blood spots (fpDBS) and capillary electrophoresis for carbohydrate deficient transferrin (CDT) screening in forensic toxicology.

    Science.gov (United States)

    Bertaso, Anna; Sorio, Daniela; Vandoros, Anthula; De Palo, Elio F; Bortolotti, Federica; Tagliaro, Franco

    2016-10-01

    Continued progress in chronic alcohol abuse investigation requires the development of less invasive procedures for screening purposes. The application of finger-prick and related dried blood spots (fpDBS) for carbohydrate deficient transferrin (CDT) detection appears suitable for this aim. Therefore, the goal of this project was to develop a screening method for CDT using fpDBS with CZE analysis. Blood samples prepared by finger-prick were placed on DBS cards and left to air dry; each dried fpDBS disc was shredded into small pieces and suspended in acid solution (60 μL of HCl 120 mmol/L). After centrifugation (10 min at 1500 × g), the collected sample was adjusted to pH 3.5. After an overnight incubation, the pH was neutralised and an iron rich solution was added. After 1 h, CZE analysis was carried out. A group of 47 individuals was studied. Parallel serum samples were collected from each investigated subject and the %CDT for each sample was measured using HPLC and CZE techniques. The fpDBS transferrin sialo isoform electropherograms were similar to those obtained with serum. Moreover, fpDBS CZE CDT percentage levels demonstrated significant statistical correlation with those obtained from serum for both HPLC and CZE %CDT (p < 0.01; r 2 = 0.8913 and 0.8976, respectively), with %CDT from 0.8 to 13.7% for fpDBS and from 0.7 to 12.7% for serum. The newly developed fpDBS procedure for CDT analysis provides a simple and inexpensive tool for use in population screening. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Veterinary Molecular Diagnostics

    NARCIS (Netherlands)

    Roest, H.I.J.; Engelsma, M.Y.; Weesendorp, E.; Bossers, A.; Elbers, A.R.W.

    2017-01-01

    In veterinary molecular diagnostics, samples originating from animals are tested. Developments in the farm animals sector and in our societal attitude towards pet animals have resulted in an increased demand for fast and reliable diagnostic techniques. Molecular diagnostics perfectly matches this

  1. Diagnostic Performance of an Advanced Modeled Iterative Reconstruction Algorithm for Low-Contrast Detectability with a Third-Generation Dual-Source Multidetector CT Scanner: Potential for Radiation Dose Reduction in a Multireader Study.

    Science.gov (United States)

    Solomon, Justin; Mileto, Achille; Ramirez-Giraldo, Juan Carlos; Samei, Ehsan

    2015-06-01

    To assess the effect of radiation dose reduction on low-contrast detectability by using an advanced modeled iterative reconstruction (ADMIRE; Siemens Healthcare, Forchheim, Germany) algorithm in a contrast-detail phantom with a third-generation dual-source multidetector computed tomography (CT) scanner. A proprietary phantom with a range of low-contrast cylindrical objects, representing five contrast levels (range, 5-20 HU) and three sizes (range, 2-6 mm) was fabricated with a three-dimensional printer and imaged with a third-generation dual-source CT scanner at various radiation dose index levels (range, 0.74-5.8 mGy). Image data sets were reconstructed by using different section thicknesses (range, 0.6-5.0 mm) and reconstruction algorithms (filtered back projection [FBP] and ADMIRE with a strength range of three to five). Eleven independent readers blinded to technique and reconstruction method assessed all data sets in two reading sessions by measuring detection accuracy with a two-alternative forced choice approach (first session) and by scoring the total number of visible object groups (second session). Dose reduction potentials based on both reading sessions were estimated. Results between FBP and ADMIRE were compared by using both paired t tests and analysis of variance tests at the 95% significance level. During the first session, detection accuracy increased with increasing contrast, size, and dose index (diagnostic accuracy range, 50%-87%; interobserver variability, ±7%). When compared with FBP, ADMIRE improved detection accuracy by 5.2% on average across the investigated variables (P material is available for this article. RSNA, 2015

  2. Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients.

    Science.gov (United States)

    Meng, Xiaodan; Joosse, Simon A; Müller, Volkmar; Trillsch, Fabian; Milde-Langosch, Karin; Mahner, Sven; Geffken, Maria; Pantel, Klaus; Schwarzenbach, Heidi

    2015-11-03

    Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC. Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines. Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I-II and III-IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III-IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III-IV (P=0.02). Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.

  3. Diagnostic accuracy of modified CT severity index in assessing severity of acute pancreatitis

    International Nuclear Information System (INIS)

    Rehan, A.; Shaukat, A.

    2016-01-01

    Objective: To determine the diagnostic accuracy of serum iron and total iron binding capacity (TIBC) in detection of iron deficiency. Study Design: Descriptive, analytical study. Place and Duration of Study: Department of Chemical Pathology and Endocrinology, from January 2013 to October 2015. Methodology: Data of 1,815 patients with results of serum iron, TIBC and ferritin from January 2013 to October 2015 was retrieved from Laboratory information System (LIMS) of AFIP. Diagnostic Accuracy Studies (STARD) guidelines were followed. Subjects of either gender, aged 1 - 68 years were included. Cases with raised serum ferritin levels (male > 336 ng/ml, female > 307 ng/ml) were excluded. Serum Ferritin was taken as gold standard with specificity of 99% and sensitivity of 80% at concentration of 30 ng/ml. Transferrin saturation was determined by dividing serum iron by TIBC and multiplying by 100. Results: Out of 1,815 subjects, 931 (51.29%) were males and 884 (48.71%) were females. The median age of the patients were 29.1 years (Inter-quartile range, IQR 19.1). Taking ferritin as gold standard, the sensitivity and specificity of serum iron was 63.5% and 38.6%, respectively; while that of TIBC was 64.5 % and 42.8%, respectively. Ferritin showed poor correlation with iron, TIBC and transferrin saturation. Conclusion: Serum iron and TIBC give no additional information in the diagnosis of iron deficiency anemia and these tests are redundant for the diagnosis of iron deficiency state, if serum ferritin is available. (author)

  4. High Power Microwave Diagnostic for the Fusion Energy Experiment ITER

    DEFF Research Database (Denmark)

    Korsholm, Søren Bang; Leipold, Frank; Gonçalves, B.

    2016-01-01

    Microwave diagnostics will play an increasingly important role in burning plasma fusion energy experiments like ITER and beyond. The Collective Thomson Scattering (CTS) diagnostic to be installed at ITER is an example of such a diagnostic with great potential in present and future experiments...

  5. Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging

    Directory of Open Access Journals (Sweden)

    Estrada Giovani

    2010-03-01

    Full Text Available Abstract Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB, a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical

  6. Polymeric LabChip real-time PCR as a point-of-care-potential diagnostic tool for rapid detection of influenza A/H1N1 virus in human clinical specimens.

    Directory of Open Access Journals (Sweden)

    Hyun-Ok Song

    Full Text Available It is clinically important to be able to detect influenza A/H1N1 virus using a fast, portable, and accurate system that has high specificity and sensitivity. To achieve this goal, it is necessary to develop a highly specific primer set that recognizes only influenza A viral genes and a rapid real-time PCR system that can detect even a single copy of the viral gene. In this study, we developed and validated a novel fluidic chip-type real-time PCR (LabChip real-time PCR system that is sensitive and specific for the detection of influenza A/H1N1, including the pandemic influenza strain A/H1N1 of 2009. This LabChip real-time PCR system has several remarkable features: (1 It allows rapid quantitative analysis, requiring only 15 min to perform 30 cycles of real-time PCR. (2 It is portable, with a weight of only 5.5 kg. (3 The reaction cost is low, since it uses disposable plastic chips. (4 Its high efficiency is equivalent to that of commercially available tube-type real-time PCR systems. The developed disposable LabChip is an economic, heat-transferable, light-transparent, and easy-to-fabricate polymeric chip compared to conventional silicon- or glass-based labchip. In addition, our LabChip has large surface-to-volume ratios in micro channels that are required for overcoming time consumed for temperature control during real-time PCR. The efficiency of the LabChip real-time PCR system was confirmed using novel primer sets specifically targeted to the hemagglutinin (HA gene of influenza A/H1N1 and clinical specimens. Eighty-five human clinical swab samples were tested using the LabChip real-time PCR. The results demonstrated 100% sensitivity and specificity, showing 72 positive and 13 negative cases. These results were identical to those from a tube-type real-time PCR system. This indicates that the novel LabChip real-time PCR may be an ultra-fast, quantitative, point-of-care-potential diagnostic tool for influenza A/H1N1 with a high sensitivity and

  7. Diagnostic relevance of radioiron-absorption-measurements and immunoradiometric serum-ferritin-assay in the evaluation of iron stores

    International Nuclear Information System (INIS)

    Heinrich, H.C.

    1978-01-01

    Negative iron balance and enhanced iron demand respectively causes deficient iron stores (prelatent iron deficiency) with increased iron absorption, later on decrease of serum iron and increase of transferrin (latent Fe deficiency) and at least iron deficient anemia (manifest iron deficiency). In prelatend iron deficiency diagnostic 59 Fe 2+ absorption is increased and the RES cells do not show storage iron cytochemically. In latent iron deficiency in addition serum iron, transferrin iron saturation and serum ferritin is decreased and hypochromic mikrocytic anemia completes the signs of manifest iron deficiency. Besides rare cases of primary hemochromatosis and marked hyperdasia of ineffective erythropoiesis in homocygotic beta-thalassemia, hereditary non-spherocytic hemolytic anemia caused by pyruvate kinase deficiency and some sideroblastic anemias increased 59 Fe 2+ absorption is a reliable measure of exhausted iron stores. In these exceptional cases differential diagnosis between sideroachrestic and siderosensitive iron deficiency anemia can be made by measurement of serum iron and serum ferritin respectively. The etiology of iron deficiency is to be cleared by measurement of 59 Fe absorption from 59 Fe 2+ and 59 Fe-marked meat with consecutive estimation of whole body 59 Fe elimination. Shortly after completion or during oral iron therapy serum ferritin concentration is not suitable to evaluate the content of iron stores. (orig.) [de

  8. In-service diagnostics of pumping facilities

    International Nuclear Information System (INIS)

    Jaros, I.

    1987-01-01

    The potential is discussed of technical diagnostics in increasing operating reliability of pumping facilities of conventional and nuclear power plants, and in rationalizing the system of their maintenance. Attention is focused on the selection of diagnostic parameters in which the so-called subjective expert methodology is applied, and on the diagnostic system design. At this stage, the construction of the respective facility and the analysis of the failure rate of its individual assemblies should be considered. The selection of diagnostic means directly depends on the selection of diagnostic parameters and is conditional on other factors, such as availability, cost, technical service, and operator's training. Briefly characterized are Czechoslovak standards assessing the mechanical condition of rotary machines from the measurement of the effective value of the rate of their oscillations. (Z.M.)

  9. Diagnostic errors in pediatric radiology

    International Nuclear Information System (INIS)

    Taylor, George A.; Voss, Stephan D.; Melvin, Patrice R.; Graham, Dionne A.

    2011-01-01

    Little information is known about the frequency, types and causes of diagnostic errors in imaging children. Our goals were to describe the patterns and potential etiologies of diagnostic error in our subspecialty. We reviewed 265 cases with clinically significant diagnostic errors identified during a 10-year period. Errors were defined as a diagnosis that was delayed, wrong or missed; they were classified as perceptual, cognitive, system-related or unavoidable; and they were evaluated by imaging modality and level of training of the physician involved. We identified 484 specific errors in the 265 cases reviewed (mean:1.8 errors/case). Most discrepancies involved staff (45.5%). Two hundred fifty-eight individual cognitive errors were identified in 151 cases (mean = 1.7 errors/case). Of these, 83 cases (55%) had additional perceptual or system-related errors. One hundred sixty-five perceptual errors were identified in 165 cases. Of these, 68 cases (41%) also had cognitive or system-related errors. Fifty-four system-related errors were identified in 46 cases (mean = 1.2 errors/case) of which all were multi-factorial. Seven cases were unavoidable. Our study defines a taxonomy of diagnostic errors in a large academic pediatric radiology practice and suggests that most are multi-factorial in etiology. Further study is needed to define effective strategies for improvement. (orig.)

  10. Diagnostic Development on NSTX

    International Nuclear Information System (INIS)

    A.L. Roquemore; D. Johnson; R. Kaita; et al

    1999-01-01

    Diagnostics are described which are currently installed or under active development for the newly commissioned NSTX device. The low aspect ratio (R/a less than or equal to 1.3) and low toroidal field (0.1-0.3T) used in this device dictate adaptations in many standard diagnostic techniques. Technical summaries of each diagnostic are given, and adaptations, where significant, are highlighted

  11. TFTR diagnostic vacuum controller

    International Nuclear Information System (INIS)

    Olsen, D.; Persons, R.

    1981-01-01

    The TFTR diagnostic vacuum controller (DVC) provides in conjunction with the Central Instrumentation Control and Data Acquisition System (CICADA), control and monitoring for the pumps, valves and gauges associated with each individual diagnostic vacuum system. There will be approximately 50 systems on TFTR. Two standard versions of the controller (A and B) wil be provided in order to meet the requirements of two diagnostic manifold arrangements. All pump and valve sequencing, as well as protection features, will be implemented by the controller

  12. Tube potential can be lowered to 80 kVp in test bolus phase of CT coronary angiography (CTCA) and CT pulmonary angiography (CTPA) to save dose without compromising diagnostic quality

    International Nuclear Information System (INIS)

    Rodrigues, J.C.L.; Manghat, N.E.; Hamilton, M.C.K.; Joshi, D.; Lyen, S.M.; Negus, I.S.

    2014-01-01

    The purpose of this study was to determine whether performing the test bolus (TB) of computed tomography coronary angiography (CTCA) and computed tomography pulmonary angiography (CTPA) at 80 kVp reduces dose without compromising diagnostic quality. An 80 kVp TB protocol for CTCA and CTPA was retrospectively compared to standard TB protocol (non-obese: 100 kVp, obese: 120 kVp). CT angiogram parameters were unchanged between cohorts. Thirty-seven consecutive 80 kVp TB CTCA images were compared to 53 standard CTCA images. Fifty consecutive CTPAs from each protocol were analysed. Diagnostic quality of the CT angiogram was assessed by: mean attenuation, signal-to-noise ratio (SNR) in the ascending aorta (AA) in CTCA and in the main pulmonary artery (MPA) in CTPA, diagnostic rate, and number of repeated monitoring scans. Mean effective dose was estimated using the dose-length product. Mean TB effective doses were significantly lower (P < 0.0001) for 80 kVp scans compared to the standard in non-obese CTCA (0.15 ± 0.04 mSv Vs 0.33 ± 0.09 mSv), obese CTCA (0.17 ± 0.06 mSv Vs 0.57 ± 0.12 mSv), and CTPA patients (0.07 ± 0.03 mSv Vs 0.15 ± 0.06 mSv). No difference was demonstrated in mean attenuation, SNR (AA), SNR (MPA), diagnostic rates, or number of repeated monitoring scans between protocols. Routinely performing TB at 80 kVp, regardless of body habitus, in CTCA and CTPA results in a small but significant dose reduction, without compromising CT angiogram diagnostic quality. (orig.)

  13. Tube potential can be lowered to 80 kVp in test bolus phase of CT coronary angiography (CTCA) and CT pulmonary angiography (CTPA) to save dose without compromising diagnostic quality

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, J.C.L.; Manghat, N.E.; Hamilton, M.C.K. [University Hospitals Bristol NHS Foundation Trust, Department of Radiology, Bristol Royal Infirmary, Bristol (United Kingdom); University Hospitals Bristol NHS Foundation Trust, National Institute for Health Research (NIHR) Cardiovascular Biomedical Research Unit, Bristol Heart Institute, Bristol Royal Infirmary, Bristol (United Kingdom); Joshi, D.; Lyen, S.M. [University Hospitals Bristol NHS Foundation Trust, Department of Radiology, Bristol Royal Infirmary, Bristol (United Kingdom); Negus, I.S. [University Hospitals Bristol NHS Foundation Trust, Department of Medical Physics and Bioengineering, Bristol Royal Infirmary, Bristol (United Kingdom)

    2014-10-15

    The purpose of this study was to determine whether performing the test bolus (TB) of computed tomography coronary angiography (CTCA) and computed tomography pulmonary angiography (CTPA) at 80 kVp reduces dose without compromising diagnostic quality. An 80 kVp TB protocol for CTCA and CTPA was retrospectively compared to standard TB protocol (non-obese: 100 kVp, obese: 120 kVp). CT angiogram parameters were unchanged between cohorts. Thirty-seven consecutive 80 kVp TB CTCA images were compared to 53 standard CTCA images. Fifty consecutive CTPAs from each protocol were analysed. Diagnostic quality of the CT angiogram was assessed by: mean attenuation, signal-to-noise ratio (SNR) in the ascending aorta (AA) in CTCA and in the main pulmonary artery (MPA) in CTPA, diagnostic rate, and number of repeated monitoring scans. Mean effective dose was estimated using the dose-length product. Mean TB effective doses were significantly lower (P < 0.0001) for 80 kVp scans compared to the standard in non-obese CTCA (0.15 ± 0.04 mSv Vs 0.33 ± 0.09 mSv), obese CTCA (0.17 ± 0.06 mSv Vs 0.57 ± 0.12 mSv), and CTPA patients (0.07 ± 0.03 mSv Vs 0.15 ± 0.06 mSv). No difference was demonstrated in mean attenuation, SNR (AA), SNR (MPA), diagnostic rates, or number of repeated monitoring scans between protocols. Routinely performing TB at 80 kVp, regardless of body habitus, in CTCA and CTPA results in a small but significant dose reduction, without compromising CT angiogram diagnostic quality. (orig.)

  14. Psychologists' diagnostic processes during a diagnostic interview

    NARCIS (Netherlands)

    Groenier, Marleen; Beerthuis, Vos R.J.; Pieters, Julius Marie; Witteman, C.L.M.; Witteman, Cilia L.M.; Swinkels, Jan A.

    2011-01-01

    In mental health care, psychologists assess clients’ complaints, analyze underlying problems, and identify causes for these problems, to make treatment decisions. We present a study on psychologists’ diagnostic processes, in which a mixed-method approach was employed. We aimed to identify a common

  15. Laboratory diagnostics of malaria

    Science.gov (United States)

    Siahaan, L.

    2018-03-01

    Even now, malaria treatment should only be administered after laboratory confirmation. There are several principal methods for diagnosing malaria. All these methods have their disadvantages.Presumptive treatment of malaria is widely practiced where laboratory tests are not readily available. Microscopy of Giemsa-stained thick and thin blood films remains the gold standard for the diagnosis of malaria infection. The technique of slide preparation, staining and reading are well known and standardized, and so is the estimate of the parasite density and parasite stages. Microscopy is not always available or feasible at primary health services in limited resource settings due to cost, lack of skilled manpower, accessories and reagents required. Rapid diagnostic tests (RDTs) are potential tools for parasite-based diagnosis since the tests are accurate in detecting malaria infections and are easy to use. The test is based on the capture of parasite antigen that released from parasitized red blood cells using monoclonal antibodies prepared against malaria antigen target. Polymerase Chain Reaction (PCR), depend on DNA amplification approaches and have higher sensitivity than microscopy. PCR it is not widely used due to the lack of a standardized methodology, high costs, and the need for highly-trained staff.

  16. Radiologic diagnostics of dementia

    International Nuclear Information System (INIS)

    Essig, M.; Schoenberg, S.O.

    2003-01-01

    Dementia is one of the most common diseases in the elderly population and is getting more and more important with the ageing of the population. A radiologic structural examination with CT or MRI is meanwhile a standard procedure in the diagnostic work up of patients with dementia syndrome. Radiology enables an early diagnosis and a differential diagnosis between different causes of dementia. Because structural changes occur only late in the disease process, a more detailed structural analysis using volumetric techniques or the use of functional imaging techniques is mandatory. These days, structural imaging uses MRI which enables to detect early atrophic changes at the medial temporal lobe with focus on the amygdala hippocampal complex. These changes are also present in the normal ageing process. In patients with Alzheimer's disease, however, they are more rapid and more pronounced. The use of functional imaging methods such as perfusion MRI, diffusion MRI or fMRI allow new insights into the pathophysiologic changes of dementia. The article gives an overview of the current status of structural imaging and an outlook into the potential of functional imaging methods. Detailed results of structural and functional imaging are presented in other articles of this issue. (orig.) [de

  17. Diagnostic nerve ultrasonography

    International Nuclear Information System (INIS)

    Baeumer, T.; Grimm, A.; Schelle, T.

    2017-01-01

    For the diagnostics of nerve lesions an imaging method is necessary to visualize peripheral nerves and their surrounding structures for an etiological classification. Clinical neurological and electrophysiological investigations provide functional information about nerve lesions. The information provided by a standard magnetic resonance imaging (MRI) examination is inadequate for peripheral nerve diagnostics; however, MRI neurography is suitable but on the other hand a resource and time-consuming method. Using ultrasonography for peripheral nerve diagnostics. With ultrasonography reliable diagnostics of entrapment neuropathies and traumatic nerve lesions are possible. The use of ultrasonography for neuropathies shows that a differentiation between different forms is possible. Nerve ultrasonography is an established diagnostic tool. In addition to the clinical examination and clinical electrophysiology, structural information can be obtained, which results in a clear improvement in the diagnostics. Ultrasonography has become an integral part of the diagnostic work-up of peripheral nerve lesions in neurophysiological departments. Nerve ultrasonography is recommended for the diagnostic work-up of peripheral nerve lesions in addition to clinical and electrophysiological investigations. It should be used in the clinical work-up of entrapment neuropathies, traumatic nerve lesions and spacy-occupying lesions of nerves. (orig.) [de

  18. Ongoing experiments: diagnostics requirements

    International Nuclear Information System (INIS)

    Dickerman, C.E.

    1976-01-01

    The paper reviews the fuel motion diagnostics needs for ongoing LMFBR safety experiments over approximately the next five years, with the discussion centered on TREAT. Brief comments on the direction in which clad motion diagnostics requirements are expected to develop are also presented

  19. Clinical diagnostic ultrasound

    International Nuclear Information System (INIS)

    Barnett, E.; Morley, P.

    1986-01-01

    This textbook on diagnostic ultrasound covers the main systems, with emphasis being placed on the clinical application of diagnostic ultrasound in everyday practice. It provides not only a textbook for postgraduates (particularly FRCR candidates), but also a reference work for practitioners of clinical ultrasound and clinicians generally

  20. Gearbox vibration diagnostic analyzer

    Science.gov (United States)

    1992-01-01

    This report describes the Gearbox Vibration Diagnostic Analyzer installed in the NASA Lewis Research Center's 500 HP Helicopter Transmission Test Stand to monitor gearbox testing. The vibration of the gearbox is analyzed using diagnostic algorithms to calculate a parameter indicating damaged components.

  1. Template-directed covalent conjugation of DNA to native antibodies, transferrin and other metal-binding proteins

    Science.gov (United States)

    Rosen, Christian B.; Kodal, Anne L. B.; Nielsen, Jesper S.; Schaffert, David H.; Scavenius, Carsten; Okholm, Anders H.; Voigt, Niels V.; Enghild, Jan J.; Kjems, Jørgen; Tørring, Thomas; Gothelf, Kurt V.

    2014-09-01

    DNA-protein conjugates are important in bioanalytical chemistry, molecular diagnostics and bionanotechnology, as the DNA provides a unique handle to identify, functionalize or otherwise manipulate proteins. To maintain protein activity, conjugation of a single DNA handle to a specific location on the protein is often needed. However, preparing such high-quality site-specific conjugates often requires genetically engineered proteins, which is a laborious and technically challenging approach. Here we demonstrate a simpler method to create site-selective DNA-protein conjugates. Using a guiding DNA strand modified with a metal-binding functionality, we directed a second DNA strand to the vicinity of a metal-binding site of His6-tagged or wild-type metal-binding proteins, such as serotransferrin, where it subsequently reacted with lysine residues at that site. This method, DNA-templated protein conjugation, facilitates the production of site-selective protein conjugates, and also conjugation to IgG1 antibodies via a histidine cluster in the constant domain.

  2. A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia

    Science.gov (United States)

    Yang, Zhaogang; Yu, Bo; Zhu, Jing; Huang, Xiaomeng; Xie, Jing; Xu, Songlin; Yang, Xiaojuan; Wang, Xinmei; Yung, Bryant C.; Lee, L. James; Lee, Robert J.; Teng, Lesheng

    2014-07-01

    The siRNA LOR-1284 targets the R2 subunit of ribonucleotide reductase (RRM2) and has shown promise in cancer therapy. In this study, transferrin (Tf) conjugated lipid nanoparticles (Tf-NP-LOR-1284) were synthesized by microfluidic hydrodynamic focusing (MHF) and evaluated for the targeted delivery of LOR-1284 siRNA into acute myeloid leukemia (AML) cells. The in vitro study showed that Tf-NP-LOR-1284 can protect LOR-1284 from serum nuclease degradation. Selective uptake of Tf-NP-LOR-1284 was observed in MV4-11 cells. In addition, qRT-PCR and Western blot results revealed that Tf-NP-LOR-1284 was more effective than the free LOR-1284 in reducing the R2 mRNA and protein levels. The Tf-NP-LOR-1284 showed prolonged circulation time and increased AUC after i.v. administration relative to the free LOR-1284. Furthermore, Tf-NP-LOR-1284 facilitated increased accumulation at the tumor site along with the decreased R2 mRNA and protein expression in a murine xenograft model. These results suggest that Tf-conjugated NPs prepared by MHF provide a suitable platform for efficient and specific therapeutic delivery of LOR-1284 into AML cells.

  3. Determination of bone blood supply with /sup 99m/Tc red blood cells and /sup 113m/In transferrin in fractures of femoral neck: concise communication

    Energy Technology Data Exchange (ETDEWEB)

    Kempi, V.; Sandegard, J.

    1982-05-01

    The uptake of in vivo labeled /sup 99m/Tc RBCs and /sup 113/In transferrin was studied in femoral bone of 21 patients who had recent operations for fracture of the femoral neck. Femoral bone biopsies and blood samples were obtained during the operation. The activity values for bone biopsies, erythrocytes, and serum were determined, and the uptake ratios between bone and erythrocyte cpm/g and between bone and serum were calculated. Biopsy samples were taken from the femoral head in 21 cases and from the trochanteric region in 14. The activity ratios for the two tracers correlated well: r . 0.94 for femoral head biopsies (P less than 0.001) and r . 0.98 for samples from the trochanteric region (P less than 0.001). Thus, the procedures are interchangeable and either may be valuable in assessing bone blood supply. An additional patient, studied only with /sup 99m/Tc RBCs, had a subsequent operation for nonunion of a fracture. Samples of both cancellous and cortical bone were obtained from the removed head. The activity ratios for the two types of bone tissue differed significantly (P . 0.02).

  4. Determination of bone blood supply with /sup 99m/Tc red blood cells and /sup 113m/In transferrin in fractures of femoral neck: concise communication

    International Nuclear Information System (INIS)

    Kempi, V.; Sandegard, J.

    1982-01-01

    The uptake of in vivo labeled /sup 99m/Tc RBCs and 113 In transferrin was studied in femoral bone of 21 patients who had recent operations for fracture of the femoral neck. Femoral bone biopsies and blood samples were obtained during the operation. The activity values for bone biopsies, erythrocytes, and serum were determined, and the uptake ratios between bone and erythrocyte cpm/g and between bone and serum were calculated. Biopsy samples were taken from the femoral head in 21 cases and from the trochanteric region in 14. The activity ratios for the two tracers correlated well: r . 0.94 for femoral head biopsies (P less than 0.001) and r . 0.98 for samples from the trochanteric region (P less than 0.001). Thus, the procedures are interchangeable and either may be valuable in assessing bone blood supply. An additional patient, studied only with /sup 99m/Tc RBCs, had a subsequent operation for nonunion of a fracture. Samples of both cancellous and cortical bone were obtained from the removed head. The activity ratios for the two types of bone tissue differed significantly

  5. Interaction between holo transferrin and HSA-PPIX complex in the presence of lomefloxacin: An evaluation of PPIX aggregation in protein-protein interactions

    Science.gov (United States)

    Sattar, Zohreh; Iranfar, Hediye; Asoodeh, Ahmad; Saberi, Mohammad Reza; Mazhari, Mahboobeh; Chamani, Jamshidkhan

    2012-11-01

    Human serum albumin (HSA) and holo transferrin (TF) are two serum carrier proteins that are able to interact with each other, thereby altering their binding behavior toward their ligands. During the course of this study, the interaction between HSA-PPIX and TF, in the presence and absence of lomefloxacin (LMF), was for the first time investigated using different spectroscopic and molecular modeling techniques. Fluorescence spectroscopy experiments were performed in order to study conformational changes of proteins. The RLS technique was utilized to investigate the effect of LMF on J-aggregation of PPIX, which is the first report of its kind. Our findings present clear-cut evidence for the alteration of interactions between HSA and TF in the presence of PPIX and changes in drug-binding to HSA and HSA-PPIX complex upon interaction with TF. Moreover, molecular modeling studies suggested that the binding site for LMF became switched in the presence of PPIX, and that LMF bound to the site IIA of HSA. The obtained results should give new insight into research in this field and may cast some light on the dynamics of drugs in biological systems.

  6. Mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low pH compartment and infect cells

    International Nuclear Information System (INIS)

    Wang Enxiu; Obeng-Adjei, Nyamekye; Ying Qihua; Meertens, Laurent; Dragic, Tanya; Davey, Robert A.; Ross, Susan R.

    2008-01-01

    Mouse mammary tumor virus (MMTV) is a pH-dependent virus that uses mouse transferrin receptor 1 (TfR1) for entry into cells. Previous studies demonstrated that MMTV could induce pH 5-dependent fusion-from-with of mouse cells. Here we show that the MMTV envelope-mediated cell-cell fusion requires both the entry receptor and low pH (pH 5). Although expression of the MMTV envelope and TfR1 was sufficient to mediate low pH-dependent syncytia formation, virus infection required trafficking to a low pH compartment; infection was independent of cathepsin-mediated proteolysis. Human TfR1 did not support virus infection, although envelope-mediated syncytia formation occurred with human cells after pH 5 treatment and this fusion depended on TfR1 expression. However, although the MMTV envelope bound human TfR1, virus was only internalized and trafficked to a low pH compartment in cells expressing mouse TfR1. Thus, while human TfR1 supported cell-cell fusion, because it was not internalized when bound to MMTV, it did not function as an entry receptor. Our data suggest that MMTV uses TfR1 for all steps of entry: cell attachment, induction of the conformational changes in Env required for membrane fusion and internalization to an appropriate acidic compartment

  7. Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs.

    Directory of Open Access Journals (Sweden)

    Jason T Kaelber

    Full Text Available Parvoviruses exploit transferrin receptor type-1 (TfR for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species modified the interactions with parvovirus capsids by reducing the level of binding. These data, along with signatures of positive selection in the TFRC gene, are consistent with an evolutionary arms race between the TfR of the Caniform clade and parvoviruses. As well as the modifications of amino acid sequence which modify binding, we found that a glycosylation site mutation in the TfR of dogs which provided resistance to the carnivore parvoviruses which were in circulation prior to about 1975 predates the speciation of coyotes and dogs. Because the closely-related black-backed jackal has a TfR similar to their common ancestor and lacks the glycosylation site, reconstructing this mutation into the jackal TfR shows the potency of that site in blocking binding and infection and explains the resistance of dogs until recent times. This alters our understanding of this well-known example of viral emergence by indicating that canine parvovirus emergence likely resulted from the re-adaptation of a parvovirus to the resistant receptor of a former host.

  8. Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs.

    Science.gov (United States)

    Kaelber, Jason T; Demogines, Ann; Harbison, Carole E; Allison, Andrew B; Goodman, Laura B; Ortega, Alicia N; Sawyer, Sara L; Parrish, Colin R

    2012-01-01

    Parvoviruses exploit transferrin receptor type-1 (TfR) for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species) modified the interactions with parvovirus capsids by reducing the level of binding. These data, along with signatures of positive selection in the TFRC gene, are consistent with an evolutionary arms race between the TfR of the Caniform clade and parvoviruses. As well as the modifications of amino acid sequence which modify binding, we found that a glycosylation site mutation in the TfR of dogs which provided resistance to the carnivore parvoviruses which were in circulation prior to about 1975 predates the speciation of coyotes and dogs. Because the closely-related black-backed jackal has a TfR similar to their common ancestor and lacks the glycosylation site, reconstructing this mutation into the jackal TfR shows the potency of that site in blocking binding and infection and explains the resistance of dogs until recent times. This alters our understanding of this well-known example of viral emergence by indicating that canine parvovirus emergence likely resulted from the re-adaptation of a parvovirus to the resistant receptor of a former host.

  9. Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs

    Directory of Open Access Journals (Sweden)

    Masanori Yoshinaga

    2017-05-01

    Full Text Available Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1, has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1−/− mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis.

  10. Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs.

    Science.gov (United States)

    Yoshinaga, Masanori; Nakatsuka, Yoshinari; Vandenbon, Alexis; Ori, Daisuke; Uehata, Takuya; Tsujimura, Tohru; Suzuki, Yutaka; Mino, Takashi; Takeuchi, Osamu

    2017-05-23

    Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1 -/- mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. Diagnostics on Z (invited)

    International Nuclear Information System (INIS)

    Nash, T. J.; Derzon, M. S.; Chandler, G. A.; Fehl, D. L.; Leeper, R. J.; Porter, J. L.; Spielman, R. B.; Ruiz, C.; Cooper, G.; McGurn, J.

    2001-01-01

    The 100 ns, 20 MA pinch-driver Z is surrounded by an extensive set of diagnostics. There are nine radial lines of sight set at 12 o above horizontal and each of these may be equipped with up to five diagnostic ports. Instruments routinely fielded viewing the pinch from the side with these ports include x-ray diode arrays, photoconducting detector arrays, bolometers, transmission grating spectrometers, time-resolved x-ray pinhole cameras, x-ray crystal spectrometers, calorimeters, silicon photodiodes, and neutron detectors. A diagnostic package fielded on axis for viewing internal pinch radiation consists of nine lines of sight. This package accommodates virtually the same diagnostics as the radial ports. Other diagnostics not fielded on the axial or radial ports include current B-dot monitors, filtered x-ray scintillators coupled by fiber optics to streak cameras, streaked visible spectroscopy, velocity interferometric system for any reflector, bremsstrahlung cameras, and active shock breakout measurement of hohlraum temperature. The data acquisition system is capable of recording up to 500 channels and the data from each shot is available on the Internet. A major new diagnostic presently under construction is the BEAMLET backlighter. We will briefly describe each of these diagnostics and present some of the highest-quality data from them

  12. Plasma diagnostic reflectometry

    International Nuclear Information System (INIS)

    Cohen, B.I.; Afeyan, B.B.; Garrison, J.C.; Kaiser, T.B.; Luhmann, N.C. Jr.; Domier, C.W.; Chou, A.E.; Baang, S.

    1996-01-01

    Theoretical and experimental studies of plasma diagnostic reflectometry have been undertaken as a collaborative research project between the Lawrence Livermore National Laboratory (LLNL) and the University of California Department of Applied Science Plasma Diagnostics Group under the auspices of the Laboratory Directed Research and Development Program at LLNL. Theoretical analyses have explored the basic principles of reflectometry to understand its limitations, to address specific gaps in the understanding of reflectometry measurements in laboratory experiments, and to explore extensions of reflectometry such as ultra-short-pulse reflectometry. The theory has supported basic laboratory reflectometry experiments where reflectometry measurements can be corroborated by independent diagnostic measurements

  13. Diagnostic serum glycosylation profile in patients with intellectual disability as a result of MAN1B1 deficiency

    DEFF Research Database (Denmark)

    Van Scherpenzeel, Monique; Timal, Sharita; Rymen, Daisy

    2014-01-01

    Congenital disorders of glycosylation comprise a group of genetic defects with a high frequency of intellectual disability, caused by deficient glycosylation of proteins and lipids. The molecular basis of the majority of the congenital disorders of glycosylation type I subtypes, localized...... in the cytosol and endoplasmic reticulum, has been solved. However, elucidation of causative genes for defective Golgi glycosylation (congenital disorders of glycosylation type II) remains challenging because of a lack of sufficiently specific diagnostic serum methods. In a single patient with intellectual...... disability, whole-exome sequencing revealed MAN1B1 as congenital disorder of glycosylation type II candidate gene. A novel mass spectrometry method was applied for high-resolution glycoprofiling of intact plasma transferrin. A highly characteristic glycosylation signature was observed with hybrid type N...

  14. Equipment for radiation diagnostics

    International Nuclear Information System (INIS)

    Tschunt, E.; Platz, W.

    1976-01-01

    The invention relates to an improvement of the line type of the plotter in an X-ray diagnostics apparatus enabling the production of distinguishable recordings by means of a single plot type. The construction is described explicitly. (UWI) [de

  15. National Convective Weather Diagnostic

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Current convective hazards identified by the National Convective Weather Detection algorithm. The National Convective Weather Diagnostic (NCWD) is an automatically...

  16. Diagnostic radiology: I

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    This chapter describes the historic development of diagnostic equipment for radiology. The problems associated with fluoroscope design are detailed and the current uses of updated technology, particularly digitization, are considered. Numerous historical photographs are included. 13 refs

  17. Prenatal Genetic Diagnostic Tests

    Science.gov (United States)

    ... are available for many inherited disorders. The main disadvantage is that diagnostic testing carries a very small ... chromosomes, arranged in order of size. Microarray: A technology that examines all of a person’s genes to ...

  18. Nanotechnology based diagnostics for neurological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kurek, Nicholas S; Chandra, Sathees B., E-mail: schandra@roosevelt.edu [Department of Biological, Chemical and Physical Sciences, Roosevelt University, Chicago, IL (United States)

    2012-07-01

    Nanotechnology involves probing and manipulating matter at the molecular level. Nanotechnology based molecular diagnostics have the potential to alleviate the suffering caused by many diseases, including neurological disorders, due to the unique properties of nanomaterials. Most neurological illnesses are multifactorial conditions and many of these are also classified as neurobehavioral disorders. Alzheimer's disease, Parkinson's disease, Huntington disease, cerebral ischemia, epilepsy, schizophrenia and autism spectrum disorders like Rett syndrome are some examples of neurological disorders that could be better treated, diagnosed, prevented and possibly cured using nanotechnology. In order to improve the quality of life for disease afflicted people, a wide range of nanomaterials that include gold and silica nanoparticles, quantum dots and DNA along with countless other forms of nanotechnology have been investigated regarding their usefulness in advancing molecular diagnostics. Other small scaled materials like viruses and proteins also have potential for use as molecular diagnostic tools. Information obtained from nanotechnology based diagnostics can be stored and manipulated using bioinformatics software. More advanced nanotechnology based diagnostic procedures for the acquisition of even greater proteomic and genomic knowledge can then be developed along with better ways to fight various diseases. Nanotechnology also has numerous applications besides those related to biotechnology and medicine. In this article, we will discuss and analyze many novel nanotechnology based diagnostic techniques at our disposal today. (author)

  19. Nanotechnology based diagnostics for neurological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kurek, Nicholas S.; Chandra, Sathees B., E-mail: schandra@roosevelt.edu [Department of Biological, Chemical and Physical Sciences, Roosevelt University, Chicago, IL (United States)

    2012-07-01

    Nanotechnology involves probing and manipulating matter at the molecular level. Nanotechnology based molecular diagnostics have the potential to alleviate the suffering caused by many diseases, including neurological disorders, due to the unique properties of nanomaterials. Most neurological illnesses are multifactorial conditions and many of these are also classified as neurobehavioral disorders. Alzheimer's disease, Parkinson's disease, Huntington disease, cerebral ischemia, epilepsy, schizophrenia and autism spectrum disorders like Rett syndrome are some examples of neurological disorders that could be better treated, diagnosed, prevented and possibly cured using nanotechnology. In order to improve the quality of life for disease afflicted people, a wide range of nanomaterials that include gold and silica nanoparticles, quantum dots and DNA along with countless other forms of nanotechnology have been investigated regarding their usefulness in advancing molecular diagnostics. Other small scaled materials like viruses and proteins also have potential for