16 research outputs found
Iron overload can suppress IL23 expression from human monocyte-derived dendritic cells and subsequent downstream Th17 expansion
No full textShort term and prolonged effects of irradiation on human mesenchymal stem cells
No full textBackground: Mesenchymal stem cells (MSCs) are important component of the bone marrow microenvironment and are progenitors of mesenchymal tissues. The effect of therapeutic irradiation to MSCs remains unexplored. Materials and Methods: MSCs were derived from healthy donors. Effects of irradiation with single dose (dosage ranges 2, 4, 6, 8, 12 Gy) on human MSCs were investigated. Post-irradiation cell proliferation was assessed by XTT assay and cell counting. Osteogenic and adipogenic differentiation function were evaluated after irradiation. ALP activity and calcium deposition in irradiated MSCs were quantified following osteogenic induction. Results: Irradiation inhibited proliferation of human MSCs up to 2 weeks post-irradiation but thereafter, survival cells regained normal proliferation rate back to the control level. ALP activity and calcium deposition were both reduced in a dose-dependant fashion. Maximum reduction (16% of control ALP activity and 9% of control calcium level) was noted in MSCs under 12 Gy irradiation. Adipocyte percentage was reduced by 50% in cultures that received irradiation >4 Gy. Attempts to protect the irradiated cells with 1 μM all-trans retinoic acid showed no protective effect on MSCs proliferation and differentiation. Conclusion: Irradiation damaged the capacity of human MSCs proliferation and differentiation. However, full recovery of growth and renewal ability was observed in surviving MSCs after 2 weeks.link_to_subscribed_fulltex
Congenital Rosai-Dorfman disease presenting with Anemia, thrombocytopenia, and hepatomegaly
No full textRosai-Dorfman disease(RDD) is a rare entity of non-Langerhans cell histiocytoses(non-LCH) which usually presents with bilateral painless cervical lymphadenopathy. We describe a neonate with RDD who presented with anemia, thrombocytopenia and hepatomegaly. He recovered spontaneously with conservative manage-ment. This represents an atypical presentation of RDD. Conservative management with close monitoring can be adopted for some with systemic involvement. © 2008 Wiley-Liss, Inc.link_to_subscribed_fulltex
Comparison of subcutaneous infusion needles for transfusion-dependent thalassemia patients by the intrapersonal cross-over assessment model
No full textNeedle-induced trauma is one of the major contributing factors for poor compliance in patients with thalassaemia major on iron chelation therapy. A new generation of needles is currently available on the market, but their theoretical advantages have not been tested clinically. We performed a study to compare the pros and cons of the representative prototypes from each of the new (Thalaset needle) and old (butterfly scalp vein needle) generations of needles. Patients with thalassemia major who had been receiving subcutaneous iron chelation therapy for at least 2 years were recruited. Patients using butterfly needles were instructed to switch to the newer form of needle (Thalaset) for 2.5 months and then to change back to butterfly needles for another 2.5 months. Comparison was done by the intrapersonal cross-over model using three identical sets of questionnaires collected at the beginning of the study and after the use of Thalaset and butterfly needles, respectively. Fifty-four (22 females; 32 males) patients were included in the statistical analysis. The median age was 24.1 years (range = 7.6-47.2 years). Local reactions such as pain, itchiness, tenderness, and swelling were significantly different among the three evaluation periods and were all in favor of the Thalaset needle (all with P < 0.001), even after adjusting for the intention-to-treat calculation. The Thalaset needle is significantly better than the butterfly needle in reducing needle-related trauma. It induced fewer local skin reactions such as pain, itchiness, tenderness, and swelling. However, recommendations for its routine clinical use require further cost-effectiveness analysis. © 2004 Wiley-Liss, Inc.link_to_OA_fulltex
Cytogenetic abnormalities in pediatric myelodysplastic syndrome: A report of three cases
No full textThree consecutive cases of pediatric myelodysplastic syndrome (MDS) diagnosed over a three-year period in Queen Mary Hospital, Hong Kong, were described. Depending on the classification system used, they comprised two cases of chronic myelomonocytic leukemia (CMMoL) of which one can be reclassified as juvenile chronic myeloid leukemia (JCML) and one case of refractory anemia with excess of blasts (RAEB) or an alternative diagnosis of atypical CML. Cytogenetic abnormalities were detected in all of them on examination of bone marrow cells. Of the two CMMoL, one had monosomy 21, whereas the other had hypodiploidy. The patient with RAEB had a complex karyotype of 46,X,del(X)(q24),t(1;7) (p22;q32),add(15)(q26)(8). The balanced translocation (1;7) seen in this patient was exceedingly rare and, to the best of our knowledge, was reported only twice in the literature. The karyotypic abnormalities that we saw in our patients were not well recognized in pediatric MDS. This report emphasizes the importance of cytogenetic study in children suspected of suffering from MDS, which remains a rare disorder of childhood, and a need to rationalize current classification schemes.link_to_subscribed_fulltex
Analysis of MLL-derived transcripts in infant acute monocytic leukemia with a complex translocation (1;11;4)(q21;q23;p16)
No full textIt has been proposed, on the basis of cytogenetic studies and molecular analysis of MLL-derived transcripts in acute leukemia with 11q23 rearrangement, that only one fusion gene transcript present on the der(11) chromosome is critical for leukemogenesis. This view is challenged by a recent observation in a case of leukemia with a complex translocation that results in MLL being fused in-frame to two different partner genes. We investigated a case of infant monocytic leukemia with a complex translocation, (1;11;4)(q21;q23;p16). Molecular studies revealed MLL rearrangement by both fluorescence in situ hybridization and Southern blot analysis, and MLL/AF1q, but not the reciprocal message (i.e., AF1q/MLL), was amplified by polymerase chain reaction. Sequence analysis of MLL/AF1q revealed an in-frame fusion between MLL exon 6 and the breakpoint located six bases upstream of the ATG start site for AF1q. Our data suggest that only one form of MLL fusion gene is implicated in leukemogenesis in our case to t(1;11;4). Copyright (C) 1999 Elsevier Science Inc.link_to_subscribed_fulltex
Cytogenetic characterization of childhood hepatoblastoma
No full textWe describe the cytogenetic abnormalities in two cases of childhood hepatoblastoma. The first case was of fetal histology with squamous metaplasia, and cytogenetic study showed an add(5)(q31). Although an association between hepatoblastoma and familial adenomatous polyposis is recognized, the breakpoint in this case is distal to 5q21 and most probably does not involve the APC gene at that location. The second case was of macrotrabecular histology, and cytogenetic study showed an unbalanced translocation in the form of der(4)t(1;4)(q12;q34) in a hyperdiploid clone. Including our case, der(4)t(1;4)(q12;q34) has been recognized in four cases of hepatoblastoma, and it may be the first recurrent translocation in this tumor. Understanding the molecular mechanism and clinical significance of this translocation awaits analysis of more cases. (C) 2000 Elsevier Science Inc.link_to_subscribed_fulltex
Generation of genomic-integration-free human induced pluripotent stem cells and the derived cardiomyocytes of X-linked dilated cardiomyopathy from DMD gene mutation
No full textWe derived an integration-free induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 23-year-old male patient. This
patient carries a 5′ splice site point mutation in intron 1 (c.31+1G > A) of the dystrophin gene, a mutation associated with X-linked dilated cardiomyopathy
(XLDCM). Sendai virus was used to reprogram the PBMCs and deliver OCT3/4, SOX2, c-MYC, and KLF4 factors. The iPSC line (HKUi002-A) generated preserved the
mutation, expressed common pluripotency markers, differentiated into three germ layers in vivo, and exhibited a normal karyotype. Further differentiation into
cardiomyocytes enables the study of the disease mechanisms of XLDCM
Identification of a novel distal regulatory element of the human Neuroglobin gene by the chromosome conformation capture approach
No full textNeuroglobin (NGB) is predominantly expressed in the brain and retina. Studies suggest that NGB exerts protective effects to neuronal cells and is implicated in reducing the severity of stroke and Alzheimer's disease. However, little is known about the mechanisms which regulate the cell type-specific expression of the gene. In this study, we hypothesized that distal regulatory elements (DREs) are involved in optimal expression of the NGB gene. By chromosome conformation capture we identified two novel DREs located -70 kb upstream and +100 kb downstream from the NGB gene. ENCODE database showed the presence of DNaseI hypersensitive and transcription factors binding sites in these regions. Further analyses using luciferase reporters and chromatin immunoprecipitation suggested that the -70 kb region upstream of the NGB gene contained a neuronalspecific enhancer and GATA transcription factor binding sites. Knockdown of GATA-2 caused NGB expression to drop dramatically, indicating GATA-2 as an essential transcription factor for the activation of NGB expression. The crucial role of the DRE in NGB expression activation was further confirmed by the drop in NGB level after CRISPR-mediated deletion of the DRE. Taken together, we show that the NGB gene is regulated by a cell type-specific loop formed between its promoter and the novel DRE
