368 research outputs found
Cadmium Impairs p53 Activity in HepG2 Cells
Cadmium and cadmium compounds are contaminants of the environment, food, and drinking water and are important constituents of cigarette smoke. Cd exposure has also been associated with airborne particulate CdO and with Cd-containing quantum dots in medical therapy. Adverse cadmium effects reported in the literature have stimulated during recent years an ongoing discussion to better elucidate cadmium outcomes at cell and molecular level. The present work is designed to gain an insight into the mechanism of p53 impairment at gene and protein level to understand Cd-induced resistance to apoptosis. We used a hepatoma cell line (HepG2) derived from liver, known to be metal responsive. At genotoxic cadmium concentrations no cell cycle arrest was observed. The p53 at gene and protein level was not regulated. Fluorescence images showed that p53 was correctly translocated into the nucleus but that the , a downstream protein of p53 network involved in cell cycle regulation, was not activated at the highest cadmium concentrations used. The miRNAs analysis revealed an upregulation of mir-372, an miRNA able to affect expression and promote cell cycle progression and proliferation. The role of metallothioneins and possible conformational changes of p53 are discussed
Clonal Chromosome Anomalies Affecting Fli1 Mimic Inherited Thrombocytopenia Of The Paris-Trousseau Type
Introduction: The thrombocytopenia of the Paris-Trousseau (TCPT) type is a contiguous gene syndrome characterized by mild bleeding tendency, variable thrombocytopenia (THC), abnormal giant alpha-granules in platelets and dysmegakaryopoiesis: it derives from a constitutional deletion of chromosome 11 leading to the loss of FLI1, a transcription factor involved in megakaryocyte differentiation and maturation. Case report: A women with an acquired, isolated THC developing over 10 yr showed morphological features typical of TCPT in platelets and bone marrow (BM). Twenty years after the onset of THC, the other hematological parameters are still normal and the patient is well. Results: Clonal hemopoiesis was shown and chromosome analyses performed on BM revealed a clone with 45 chromosomes and a complex unbalanced translocation involving chromosomes 2, 3, and 11. The anomaly was present in the majority of bone marrow cells but only in a few peripheral blood elements. A microarray-based comparative genomic hybridization defined the deleted region of chromosome 11 including the FLI1 locus that was missing. Conclusion: Although our patient presented with nearly all the characteristics of TCPT, her illness was acquired instead of being inherited and the most appropriate diagnosis is that of the unilineage dysplasia 'refractory THC.' This observation suggests that appropriate cytogenetic investigations should be always considered in patients with acquired THC of unknown origin
Different loss of material in recurrent chromosome 20 interstitial deletions in Shwachman-Diamond syndrome and in myeloid neoplasms
Abstract
BACKGROUND:
An interstitial deletion of the long arms of chromosome 20, del(20)(q), is frequent in the bone marrow (BM) of patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms (MPN), and it is recurrent in the BM of patients with Shwachman-Diamond syndrome (SDS), who have a 30-40% risk of developing MDS and AML.
RESULTS:
We report the results obtained by microarray-based comparative genomic hybridization (a-CGH) in six patients with SDS, and we compare the loss of chromosome 20 material with one patient with MDS, and with data on 92 informative patients with MDS/AML/MPN and del(20)(q) collected from the literature.
CONCLUSIONS:
The chromosome material lost in MDS/AML/MPN is highly variable with no identifiable common deleted regions, whereas in SDS the loss is more uniform: in 3/6 patients it was almost identical, and the breakpoints that we defined are probably common to most patients from the literature. In some SDS patients less material may be lost, due to different distal breakpoints, but the proximal breakpoint is in the same region, always leading to the loss of the EIF6 gene, an event which was related to a lower risk of MDS/AML in comparison with other patients
Deletion of chromosome 20 in bone marrow of patients with Shwachman-Diamond syndrome, loss of the EIF6 gene and benign prognosis
Shwachman-Diamond Syndrome (SDS; On-line Mendelian Inheritance in Man database number 260400) is an autosomal recessive disorder caused by mutations in the SBDS gene in at least 90% of cases (Boocock et al, 2003). It is characterized by exocrine pancreatic insufficiency, skeletal anomalies, and bone marrow failure with variable severity of neutropenia, thrombocytopenia and anaemia (Rothbaum et al, 2002). Acquired clonal chromosome anomalies are commonly found in the bone marrow (BM), being an isochromosome for the long arms of a 7, i(7)(q10), and a deletion of the long arms of a 20, del(20)(q11), the most frequent. The relationship between these chromosome changes and the risk of patients with SDS to develop myelodysplastic syndromes and acute myeloid leukaemia (MDS/AML) has been discussed (Dror, 2005). This risk increases with the age (Shimamura, 2006), and we have also shown that the acquisition of BM clonal anomalies is age-related (Maserati et al, 2009)
A homozygous contiguous gene deletion in chromosome 16p13.3 leads to autosomal recessive osteopetrosis in a Jordanian patient
Human malignant autosomal recessive osteopetrosis (ARO) is a genetically heterogeneous disorder caused by reduced bone resorption by osteoclasts. Mutations in the CLCN7 gene are responsible not only for a substantial portion of ARO patients, but also for other forms of osteopetrosis characterized by different severity and inheritance. The lack of a clear genotype/phenotype correlation makes genetic counselling a tricky issue for CLCN7-dependent osteopetrosis.
Here we characterize the first homozygous interstitial deletion in 16p13.3, detected by array Comparative Genomic Hybridization (a-CGH) in an ARO patient of Jordanian origin. The deletion involved other genes beside CLCN7, while the proband displayed a classic ARO phenotype; however her early death did not allow more extensive clinical investigations.
The identification of this novel genomic deletion involving a large part of the CLCN7 gene is of clinical relevance, especially in prenatal diagnosis, and suggests the possibility that this kind of mutation has been underestimated so far. This data highlights the need for alternative approaches to genetic analysis also in other ARO-causative genes
Isochromosome 7q10 in Shwachman Syndrome without MDS/AML and role of chromosome 7 anomalies in myeloproliferative disorders.
High-Frequency Light Rectification by Nanoscale Plasmonic Conical Antenna in Point-Contact-Insulator-Metal Architecture
Numerous efforts have been undertaken to develop rectifying antennas operating at high frequencies, especially dedicated to light harvesting and photodetection applications. However, the development of efficient high frequency rectifying antennas has been a major technological challenge both due to a lack of comprehension of the underlying physics and limitations in the fabrication techniques. Various rectification strategies have been implemented, including metal-insulator-metal traveling-wave diodes, plasmonic nanogap optical antennas, and whisker diodes, although all show limited high-frequency operation and modest conversion efficiencies. Here a new type of rectifying antenna based on plasmonic carrier generation is demonstrated. The proposed structure consists of a resonant metallic conical nano-antenna tip in contact with the oxide surface of an oxide/metal bilayer. The conical shape allows for an improved current generation based on plasmon-mediated electromagnetic-to-electron conversion, an effect exploiting the nanoscale-tip contact of the rectifying antenna, and proportional to the antenna resonance and to the surface-electron scattering. Importantly, this solution provides rectification operation at 280 THz (1064 nm) with a 100-fold increase in efficiency compared to previously reported results. Finally, the conical rectifying antenna is also demonstrated to operate at 384 THz (780 nm), hence paving a way toward efficient rectennas toward the visible range
MLL-MLLT10 fusion in acute monoblastic leukemia: variant complex rearrangements and 11q proximal breakpoint heterogeneity
Cytogenetic studies of acute monoblastic leukemia cases presenting MLL-MLLT10 (alias MLL-AF10) fusion show a broad heterogeneity of chromosomal breakpoints. We present two new pediatric cases (French-American-British type M5) with MLL-MLLT10 fusion, which we studied with fluorescence in situ hybridization. In both we detected a paracentric inversion of the 11q region that translocated onto chromosome 10p12; one case displayed a variant complex pattern. We review the cytogenetic molecular data concerning the proximal inversion breakpoint of 11q and confirm its heterogeneit
Ph-positive CML in blastic phase with monosomy 7 in a Down syndrome patient. Monitoring by interphase cytogenetics and demonstration of maternal allelic loss
We report a case of Ph-positive chronic myelocytic leukemia in blastic phase in an 11-year-old boy with Down syndrome. Monosomy 7 was the only additional chromosomal anomaly in the blastic clone. Fluorescence in situ hybridization analysis on interphase nuclei with a centromeric probe specific to chromosome 7 proved to be efficient in disease monitoring; and showed, together with the results of chromosome analysis on metaphases, that B- lymphocytes at the origin of an EBV-established line were not part of the leukemic clone. The study of DNA polymorphisms showed that the origin of the constitutional trisomy 21 was a maternal anaphase I nondisjunction, that the chromosome 7 lost in the blastic marrow clone was the maternal one, and led us to postulate that the mother's chromosomes are prone to impairment of normal disjunction. The study of allelic losses of chromosome 7 loci proved to be a further possibility for disease monitoring
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