1,721,129 research outputs found
Antibody and method for identification of dendritic cells
No full textMethod for identifying myeloid or plasmacytoid dendritic cells provided by a mammal, stimulated or unstimulated, comprising the steps of: a) preparing a cell sample; b) contacting the cell sample myeloid or plasmacytoid dendritic cells to form a complex; c) detecting the complex; characterized in that the phosphatase is the Receptor type Tyrosine Phosphatase Gamma Protein (PTPRG), acting as a specific marker of said dendritic cells, and in thaht the compound is a polypeptide capable of selectively bind to the PTPRG or to a fragment thereof or to a oligonucleotide complementary to a PTPRG mRNA logonucleotide in such a manner as to allow the selective recognizing of the dendritic cells in the cell sample
DIAGNOSIS, PROGNOSIS AND SCREENING FOR MEDICAMENTS FOR TREATMENT OF MYELOPROLIFERATIVE DISORDERS USING RECEPTOR PROTEIN TYROSINE-PHOSPHATASE GAMMA (PTPRG) AS BIOMARKER
No full textMetodo per l’identificazione del trascritto o della proteina in campioni di sangue periferico o midollo osseo provenienti da un mammifero, comprendente le fasi: a) di preparazione di un campione di cellule da esaminare; b) di messa a contatto di un campione di cellule da esaminare con un composto in grado di legarsi selettivamente ad una fosfatasi presente su dette cellule per formare un complesso o l’amplificazione mediate metodica basata sulla reazione di polimerizzazione a catena del DNA (PCR) di un trascritto specifico c) rilevazione del complesso ottenuto; caratterizzato dal fatto che la fosfatasi è la protein tirosina fosfatasi recettoriale gamma (PTPRG) e dal fatto che il composto è polipeptide in grado di legarsi selettivamente alla PTPRG od a parte di essa oppure oligonucleotide complementare a oligonucleotide dell’mRNA della PTPRG in modo da permettere il riconoscimento selettivo della presenza di detto mRNA o proteina. Tale metodo permette di riconoscere la presenza di malattie mieloproliferative croniche in quanto è possibile rilevarne un livello di espressione negli individui sani che risulta superiore rispetto agli individui affetti da patolgia mieloproiferativa cronica. Tale metodo si applica in maniera preferenziale, ma non risulta limitata alla, leucemia mieloide cronica e alla trombocitemia essenziale
Infrared spectroscopy and microscopy in cancer research and diagnosis
Full text linkSince the middle of the 20th century, infrared (IR) spectroscopy coupled to microscopy has been used as a non destructive, label free, highly sensitive and specific analytical method to reveal molecular structure. Nowadays, synchrotron based IR microspectroscopy offers a signal-to-noise spectral quality unreachable by other broadband sources, and achieves the highest optically attainable IR spatial resolution on microscopic scale samples. This is particularly relevant in Life Sciences, with a significant progression of applications in biomedical research and in particular cancer studies. In view of the validation of the IR fingerprint region as a spectral marker of cancer and anticancer therapy follow up, we have recently performed a set of key experiments on leukemic blasts at the IR beamline B22 ‘MIRIAM’. The results on identification and cross-validation of IR markers of drug actions in the spectra of K562 leukemic blasts are in the following report
InfraRed Spectroscopy and Microscopy in Cancer Research
Full text linkSince the middle of 20th century infrared (IR) spectroscopy coupled to microscopy (IR microspectroscopy) has been recognized as a non destructive, label free, highly sensitive and specific analytical method with many potential useful applications in different fields of biomedical research and in particular cancer research and diagnosis. Although many technological improvements have been made to facilitate biomedical applications of this powerful analytical technique, it has not yet properly come into the scientific background of many potential end users. Therefore, to achieve those fundamental objectives an interdisciplinary approach is needed with basic scientists, spectroscopists, biologists and clinicians who must effectively communicate and understand each other’s requirements and challenges. In this review we aim at illustrating some principles of Fourier transform (FT) Infrared (IR) vibrational spectroscopy and microscopy (microFT-IR) as a useful method to interrogate molecules in specimen by mid-IR radiation. Penetrating into basics of molecular vibrations might help us to understand whether, when and how complementary information obtained by microFT-IR could become useful in our research and/or diagnostic activities. MicroFT-IR techniques allowing to acquire information about the molecular composition and structure of a sample within a micrometric scale in a matter of seconds will be illustrated as well as some limitations will be discussed. How biochemical, structural, and dynamical information about the systems can be obtained by bench top microFTIR instrumentation will be also presented together with some methods to treat and interpret IR spectral data and applicative examples. The mid-IR absorbance spectrum is one of the most information-rich and concise way to represent the whole “...omics” of a cell and, as such, fits all the characteristics for the development of a clinically useful biomarker
Accurate prediction of the age incidence of chronic myeloid leukemia with an improved two-mutation mathematical model
No full textChronic myeloid leukemia (CML) is a malignant clonal disorder whose hallmark is a reciprocal translocation between chromosomes 9 and 22 occurring in 95% of affected patients. This translocation causes the expression of a deregulated BCR/ABL fusion oncogene and, interestingly, is detectable in healthy individuals. Based on this information we assumed that the sole presence of the BCR/ABL transcript represents a necessary but not sufficient event for the clonal expansion of CML precursors. We developed a mathematical model introducing a probability that any normal cell undergoes a first aberration, and a probability that a cell that experienced a first mutation undergoes a second mutation as well. Two variants are proposed and analyzed: in the first the probability of the first mutation is supposed to be age independent and in the second, it depends on the hemopoietic cell turnover and mass. The model parameters have been estimated by regression from the observed CML incidence curves. Our models offer a significantly improved version of existing one-step and two-steps models, as they integrate key clinical and biological data reported in the literature and accurately fit the observed incidence. Our models also estimate the increased radiation-associated mutation rate at a younger age in atomic bomb survivors. Although this work focuses on CML, the modelling approach can be applied to all types of leukemia and lymphoma
The role of macrophages and their scavenger receptors in cystic fibrosis
No full textDiscussion of the role of macrophages and their scavenger receptors in Cystic Fibrosi
EFFECTS OF AZITHROMYCIN ON REGULATION OF METALLOPROTEASES RELEASED BY PSEUDOMONAS AERUGINOSA (PA) CLINICAL STRAINS
No full textno availabl
Protein myristoylation in human mononuclear phagocytes : modulation by Interferon gamma and Tumor Necrosis Factor alpha
No full textLabelling of cells with [3H]myristic acid and analysis of labelled proteins by SDS-PAGE and fluorography, enabled the identification of a limited number of myristoylated proteins in human monocytes and monocyte-derived macrophages. In human monocytes, cultivated for one to three days, major myristoylated proteins observed were of 18 kDa, 44 kDa, 60-62 kDa, 90 kDa, and a doublet of 38-40 kDa. Differentiation of monocytes to macrophages by in vitro cultivation was accompanied by a selective decrease in the 60-62 kDa protein. Cultivation of the cells in the presence of the macrophage-activating cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), prevented the decrease in the expression of the 60-62 kDa myristoylated protein. The effect of cytokines was observed when monocytes were treated with IFN-gamma or TNF-alpha for 24 or 48 h and protein myristoylation analyzed at day four of culture. Maintenance of monocytes in culture for up to nine days in the presence of cytokines prevented the decrease in the expression of the 60-62 kDa myristoylated protein. IFN-gamma had additional effects on myristoylation of macrophage proteins. Treatment of monocytes with IFN-gamma for a few hours caused the induction of a 66 kDa protein. Induction of this myristoylated protein by IFN-gamma was time-dependent and peaked at six hours. Analysis of the subcellular distribution of the 66 kDa protein induced by IFN-gamma showed that, analogously to other myristoylated proteins, most of it was associated with cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS
Recent Developments in Chronic Myeloid Leukemia Biology and Treatment
No full textBCR-ABL1 represents a driving force in the biology of CML cell as demonstrated by the spectacular results of tyrosine kinase inhibitor (TKI) therapies. Imatinib is a highly effective therapy for chronic phase-chronic myeloid leukaemia (CP-CML) patients, as it turned CML blastic transformation into a rare event. However, responses to frontline imatinib are variable and 2nd- (nilotinib, dasatinib and bosutinib) or 3rd-generation (ponatinib) TKIs have been developed to face BCR-ABL1 mutation-induced imatinib resistance, or intolerance. Nilotinib and dasatinib have been licensed also for the frontline treatment of newly diagnosed patients and they proved to be more effective than imatinib in inducing earlier and deeper molecular responses. However, the reappearance of leukemic cells after TKI discontinuation also in patients with stable negative minimal residual disease highlighted the concept of persistence of BCR-ABL1 leukemia stem cells. Data have accumulated in the past years that the BCR-ABL1 oncogene does not operate alone to drive disease emergence, maintenance and progression: These issues will be briefly reviewed with a special focus on the emerging role of phosphatases in the pathogenesis of hematologic malignancies as new therapeutic approaches have been proposed based on findings in basic science laboratories. Critical issues and future trends will be discussed including the need to better characterize patients according to prognostic scores, paying more attention to those at high risk for disease progression, the increased importance of early monitoring and the optimization of treatment in order to provide an “operational cure” (discontinuation of treatment) in a considerable proportion of patients
Identification of Protein Tyrosine Phosphatase Receptor Gamma Extracellular Domain (sPTPRG) as a Natural Soluble Protein in Plasma
Full text linkPTPRG is a widely expressed protein tyrosine phosphatase present in various isoforms. Peptides from its extracellular domain have been detected in plasma by proteomic techniques. We aim at characterizing the plasmatic PTPRG (sPTPRG) form and to identify its source.The expression of sPTPRG was evaluated in human plasma and murine plasma and tissues by immunoprecipitation and Western blotting. The polypeptides identified have an apparent Mr of about 120 kDa (major band) and 90 kDa (minor band) respectively. Full length PTPRG was identified in the 100.000×g pelleted plasma fraction, suggesting that it was present associated to cell-derived vesicles (exosomes). The release of sPTPRG by HepG2 human hepatocellular carcinoma cell line was induced by ethanol and sensitive to metalloproteinase and not to Furin inhibitors. Finally, increased levels of the plasmatic ∼120 kDa isoform were associated with the occurrence of liver damage.These results demonstrate that sPTPRG represent a novel candidate protein biomarker in plasma whose increased expression is associated to hepatocyte damage. This observation could open a new avenue of investigation in this challenging field
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