Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Few human monoblastic cell lines have been characterized to date. We have established the SigM5 cell line from a patient with acute monoblastic leukaemia (FAB M5a). Original leukaemic cells had a karyotype of 47,XY,+8, whereas the cell line showed a stemline clone of 81,XX,Y,Y,1,4,6,7,+8,+8,9,10,10,11,13,16,19[cp], with a minor sideline also present. Cytochemical staining was strongly positive with alpha-naphthylbutyrate acetate esterase, particulate positive with Sudan black and weakly positive for myeloperoxidase. Cells were positive for CD13, CD15, CD18, CD23, CD33, CD38, CD45, CD68 and myeloperoxidase. CD14 expression was 3-15%. SigM5 constitutively secreted interleukin (IL)-2, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, ferritin, lysozyme, N-elastase and neopterin upon stimulation with interferon (IFN)-gamma. Cells expressed the proinflammatory mediator macrophage migration inhibitory factor (MIF). All NADPH oxidase subunits were constitutively present, but nitroblue tetrazolium reduction was only detectable upon activation with IFN-gamma. SigM5 monoblasts were sensitive to arsenic trioxide (As2O3) previously not described to induce apoptosis in monoblastic cells. Differing considerably in morphology, immunophenotype and sensitivity to arsenics from the widely used cell lines U937, HL-60 and THP-1, SigM5 is a new monoblastic cell line useful for studying leukaemogenesis, monocyte differentiation and tumour cell susceptibility to arsenic compounds.
 ...
PMID:Establishment and characterization of an arsenic-sensitive monoblastic leukaemia cell line (SigM5). 1084 31

Radiolabeled monoclonal antibodies have been used with encouraging results in conjunction with stem cell transplantation for patients with hematologic malignancies targeting a variety of surface antigens including CD33, CD45 and CD66 for leukemias, CD20 and CD22 for non-Hodgkin's lymphomas, and ferritin for Hodgkin's disease. The results obtained targeting epithelial antigens on solid tumors, however, have generally been less encouraging, primarily due to the relative insensitivity of these malignancies to ionizing radiation. In this report we review clinical studies that have incorporated myeloablative doses of targeted radiation using radiolabeled antibodies in conjunction with stem cell transplant regimens.
 ...
PMID:The use of radioimmunoconjugates in stem cell transplantation. 1205 30

The complex balance between the pro-activating and regulatory influences of the complement system can affect the pathogenesis of immune complex-mediated glomerulonephritis (ICGN). Key complement regulatory proteins include decay accelerating factor (DAF) and CD59, which inhibit C3 activation and C5b-9 generation, respectively. Both are glycosylphosphatidylinositol-linked cell membrane proteins, which are widely distributed in humans and mice. Chronic serum sickness induced by daily immunization with horse spleen apoferritin over 6 weeks was used to induce ICGN in DAF-, CD59- and DAF/CD59-deficient mice, with wild-type littermate mice serving as controls. Both DAF and DAF/CD59-deficient mice had an increased incidence of GN relative to wild-type controls associated with significantly increased glomerular C3 deposition. Disease expression in CD59-deficient mice was no different than wild-type controls. DAF- and DAF/CD59-deficient mice also had increased monocyte chemoattractant protein-1 mRNA expression and glomerular infiltration with CD45(+) leukocytes. Our findings suggest that activation of C3 is strongly associated with experimental ICGN while downstream formation of C5b-9 is of lesser pathogenic importance in this model.
 ...
PMID:Decay-accelerating factor but not CD59 limits experimental immune-complex glomerulonephritis. 1725 99

Most patients with myelodysplastic syndrome (MDS) are classified at diagnosis as having a low/INT-I or INT-II/high risk disease, based on the classical International Prognostic Scoring System (IPSS) criteria. The low/INT-I risk patients are usually managed mildly with supportive care, including red blood cell (RBC) transfusions, erythroid stimulating agents (ESAs), other cytokines (G-CSF, platelet stimulating agents), as well as thalidomide and lenalidomide. Some patients receive immunosuppressive therapy, and iron chelation is indicated in iron overloaded patients. Aggressive approach (hypomethylating agents, chemotherapy and stem cell transplantation) is usually not applied in such patients. Occasionally, we observe a "low risk" patient with rapid progression of disease and poor outcome. Can we identify demographic, clinical, laboratory, cellular-biological and/or molecular parameters that can predict "poor prognostic features" (PPF) in "low risk" MDS patients? Clinical and laboratory parameters have been reported to be associated with poor prognosis, in addition to the known "classical" IPSS criteria. These include older age, male gender, poor performance status, co-morbidities, degree of anemia, low absolute neutrophile count (ANC) and platelet counts, RBC transfusion requirements, high serum ferritin, high LDH, bone marrow (BM) fibrosis, increased number of BM CD34+ cells and multi-lineage dysplasia. Certain immunophenotypes (low CD11b, high HLA-Dr, CD34, CD13 and CD45), clonal granulocytes, multiple chromosomal abnormalities, chromosomal instability, short telomeres and high telomerase activity were also reported as PPF. Studies of apoptosis identified Bcl-2 expression and high caspase 3 as PPF, while the reports on survivin expression have been confusing. Recent exciting data suggest that methylation of p15 INK4b and of CTNNA1 (in 5q-), high level of methylation of other genes, absence of the TET2 mutation, down regulation of the lymphoid enhancer binding factor 1 (LEF1), mutation of the polycomb-associated gene ASXL1 and a specific 6-gene signature in gene expression profiling - are all associated with poor prognosis in MDS. Do we have data suggesting a different treatment for "low risk" MDS patients displaying PPF? Two teams, the combined Nordic-Italian and the GFM groups have reported an improved survival with ESAs. The GFM has achieved prolonged survival with iron chelation. Recently, encouraging data with survival advantage in azacitidine-treated patients have been published, including a few INT-I patients. Finally, data suggest that low/INT-I MDS patients who undergo stem cell transplantation (SCT0 do better than INT-II/high risk patients). In summary, some patients, classified as "low risk MDS" carry PPF. An appropriate therapeutic approach is indicated. Future updated classifications and prospective trials may lead to a better outcome.
 ...
PMID:The lower risk MDS patient at risk of rapid progression. 2057 98

The susceptibility of the aging brain to neurodegenerative disease may in part be attributed to cellular aging of the microglial cells that survey it. We investigated the effect of cellular aging induced by telomere shortening on microglia by the use of mice lacking the telomerase RNA component (TERC) and design-based stereology. TERC knockout (KO) mice had a significantly reduced number of CD11b(+) microglia in the dentate gyrus. Because of an even greater reduction in dentate gyrus volume, microglial density was, however, increased. Microglia in TERC KO mice maintained a homogenous distribution and normal expression of CD45 and CD68 and the aging marker, ferritin, but were morphologically distinct from microglia in both adult and old wild-type mice. TERC KO mice also showed increased cellular apoptosis and impaired spatial learning. Our results suggest that individual microglia are relatively resistant to telomerase deficiency during steady state conditions, despite an overall reduction in microglial numbers. Furthermore, telomerase deficiency and aging may provide disparate cues leading to distinct changes in microglial morphology and phenotype.
 ...
PMID:Telomere dysfunction reduces microglial numbers without fully inducing an aging phenotype. 2589 7