TY - JOUR. T1 - Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA double-strand break repair in nuclear extracts. AU - Li, Yuling. AU - Carty, Michael P.. AU - Oakley, Gregory G.. AU - Seidman, Michael M.. AU - Medvedovic, Mario. AU - Dixon, Kathleen. PY - 2001/1/1. Y1 - 2001/1/1. N2 - Ataxia telangiectasia (A-T) is a human genetic disorder characterized by progressive cerebellar degeneration, hypersensitivity to ionizing radiation (IR), immunodeficiency, and high cancer risk. At the cellular level, IR sensitivity and increased frequency of spontaneous and IR-induced chromosomal breakage and rearrangements are the hallmarks of A-T. The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein kinase involved in DNA double-strand break (DSB) repair and DNA damage responses. The characteristics of the A-T cellular phenotypes and ATM gene suggest that ATM may play a role similar to that of DNA-PKcs in DSB repair ...
TY - JOUR. T1 - Glutathione levels in blood from ataxia telangiectasia patients suggest in vivo adaptive mechanisms to oxidative stress. AU - Degan, Paolo. AU - dIschia, Marco. AU - Pallardó, Federico V.. AU - Zatterale, Adriana. AU - Brusco, Alfredo. AU - Calzone, Rita. AU - Cavalieri, Simona. AU - Kavakli, Kaan. AU - Lloret, Ana. AU - Manini, Paola. AU - Pisanti, Maria Antonietta. AU - Vuttariello, Emilia. AU - Pagano, Giovanni. PY - 2007/6. Y1 - 2007/6. N2 - Objective: To evaluate an in vivo pro-oxidant state in patients with ataxia telangiectasia (AT). Methods: A set of oxidative stress endpoints were measured in 9 AT homozygotes, 16 AT heterozygotes (parents) and 83 controls (grouped in age ranges as for patients and parents, respectively). The following analytes were measured: (a) leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG); (b) blood glutathione (GSSG and GSH); and (c) plasma levels of glyoxal (Glx) and methylglyoxal (MGlx). Results: AT patients displayed a significant decrease in ...
Albany, US) DelveInsight has launched a new report on Ataxia Telangiectasia Pipeline. Ataxia Telangiectasia (AT) Pipeline Insight, 2020 report by DelveInsight outlays comprehensive insights of present clinical development scenario and growth prospects across the Ataxia Telangiectasia (AT) market. A detailed picture of the Ataxia Telangiectasia (AT) pipeline landscape is provided, which includes the disease overview and Ataxia Telangiectasia (AT) treatment guidelines. The assessment part of the report embraces in-depth Ataxia Telangiectasia (AT) commercial assessment and clinical assessment of the Ataxia Telangiectasia (AT) pipeline products from the pre-clinical developmental phase to the marketed phase. In the report, a detailed description of the drug is proffered including mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Ataxia Telangiectasia (AT) collaborations, licensing, mergers and acquisition, ...
TY - JOUR. T1 - DHFR gene amplification in cultured skin fibroblasts of ataxia telangiectasia patients after methotrexate selection. AU - Lücke-huhle, Christine. AU - Hinrichs, Susanne. AU - Speit, Günter. PY - 1987/12. Y1 - 1987/12. N2 - During selection for methotrexate resistance, SV40-transformed human skin fibroblasts from patients with ataxia telangiectasia (A-T) underwent amplification of the dihydrofolate reductase (DHFR) gene, experienced nearly complete loss of the integrated SV40 sequences and showed a 3.6-fold increase in Ki-ras gene copy number. Over a period of months methotrexate-resistant (MTXr) A-T subclones were obtained, which were able to grow in progressively increasing MTX concentrations up to 100 μM. The ED50 values determined as the effective dose of MTX causing 50% growth inhibition in comparison to control cells increased from 3×10-2 μM for MTXs AT5BI-VA cells to 250 μM MTX for the MTXr AX100 subclone. In contrast, human skin fibroblasts of healthy individuals did ...
We have studied an inbred family in which two cousins presented with the same clinical features of ataxia telangiectasia (AT). Both patients are still ambulatory at ages 25 and 20. Cellular features of both patients are typical of AT and include increased radiosensitivity and an increased level of spontaneously occurring chromosome aberrations in peripheral blood lymphocytes. Linkage studies and haplotype analysis show no clear evidence that the gene for AT in this family is on chromosome 11q22-23. As previously reported AT families from complementation groups AB, C, and D have all shown linkage to this region of 11q22-23. Our study is of importance in suggesting additional locus heterogeneity.. ...
TY - JOUR. T1 - ATM mutations in patients with ataxia telangiectasia screened by a hierarchical strategy. AU - Sasaki, Tomonari. AU - Tian, Huaize. AU - Kukita, Yoji. AU - Inazuka, Masakazu. AU - Tahira, Tomoko. AU - Imai, Takashi. AU - Yamauchi, Masatake. AU - Saito, Toshiyuki. AU - Hori, Tada Aki. AU - Hashimoto-Tamaoki, Tomoko. AU - Komatsu, Kenshi. AU - Nikaido, Osamu. AU - Hayashi, Kenshi. PY - 1998/1/1. Y1 - 1998/1/1. N2 - ATM has been identified as a gene that is responsible for ataxia telangiectasia (AT), a pleiotropic disorder of autosomal recessive inheritance. While many mutations of this gene in AT patients of various ethnicities have been reported, data on Japanese patients are scarce. In this report, we present the results of a thorough survey of ATM mutations in 14 unrelated AT patients, with an emphasis on Japanese subjects. We used a hierarchical strategy in which we extensively analyzed the entire coding region of the cDNA. In the first stage, point mutations were sought by ...
Ataxia-telangiectasia (AT) is a rare progressive neurodegenerative autosomal recessive disorder characterized by cerebellar ataxia, neuromotor dysfunction, oculocutaneous telangiectasia and immunodeficiency. AT patients are vulnerable to cancer and infection and usually die during their 2nd or 3rd decade due to these complications. Life expectancy does not correlate well with severity of neurological impairment. The main cause of death is respiratory infections because these patients are known to have severe type of immunodeficiency. The immunodeficiency of AT patient consists of both humoral defect (immunoglobulin deficiency and reduced response to polysaccharide antigens) and cell-mediated defect (reduced lymphocytes number and function). Consequently, pneumonia is the most common infection seen in AT patients, and is usually caused by S. pneumoniae. Therefore, a routine schedule of pneumococcal vaccine is highly recommended in AT cases where immunoglobulin replacement therapy was not already ...
Ataxia-telangiectasia (AT) is a rare progressive neurodegenerative autosomal recessive disorder characterized by cerebellar ataxia, neuromotor dysfunction, oculocutaneous telangiectasia and immunodeficiency. AT patients are vulnerable to cancer and infection and usually die during their 2nd or 3rd decade due to these complications. Life expectancy does not correlate well with severity of neurological impairment. The main cause of death is respiratory infections because these patients are known to have severe type of immunodeficiency. The immunodeficiency of AT patient consists of both humoral defect (immunoglobulin deficiency and reduced response to polysaccharide antigens) and cell-mediated defect (reduced lymphocytes number and function). Consequently, pneumonia is the most common infection seen in AT patients, and is usually caused by S. pneumoniae. Therefore, a routine schedule of pneumococcal vaccine is highly recommended in AT cases where immunoglobulin replacement therapy was not already ...
Cellular response to DNA damage is critical to maintain genomic stability. When a double-strand break (DSB) occurs, the cell activates its checkpoint machinery to halt cell cycle progression and allow proper DSB repair (1). Without such response and repair, the cell will eventually undergo apoptosis or pass on its altered DNA to daughter cells. Checkpoints are enabled through sensing DNA damage, transducing damage signals, and activating effectors. Mechanisms by which DNA damage signals are initiated have begun to be revealed (1, 2) . PI-3-like kinases, including ataxia-telangiectasia mutated (ATM), ATM and Rad3-related (ATR), and DNA-PK are believed to play central roles (3). ATM is mutated (lost or inactivated) in the human genetic disorder ataxia-telangiectasia and could be the primary kinase responsible for DSB signaling transduction. Structural chromatin changes activate ATM, which then phosphorylates itself (4). Activated, autophosphorylated ATM in turn phosphorylates the checkpoint ...
Our experimental results establish that tissues from Atm-deficient mice are under oxidative stress and suffer oxidative damage. We and others have identified defects in molecular pathways that lead to abnormalities in the response of cells to ionizing radiation, meiosis, and T cell development where DNA double-strand breaks occur (1, 3-5, 20-23). In addition, several reports have implicated ATM as a serine protein kinase that phosphorylates p53 and chk2, leading to cell cycle arrest after ionizing radiation (24-27). Why would defects in these pathways result in oxidative stress, especially in the adult brain? The majority of cells in the central nervous system are postmitotic and there is no evidence of DNA recombination or significant DNA double-strand breaks in the central nervous system in the absence of ionizing radiation. We infer that ATM also functions to protect biomolecules other than DNA from oxidative damage. Studies from many investigators have established that lipids and proteins ...
History: Caffeine suppresses ataxia telangiectasia and Rad3 related and ataxia telangiectasia mutated (ATM) activities; ATM is usually the major kinase for DNA harm recognition. to IR. Finally, airport deoxynucleotidyl transferase-dUTP chip end labels assay. Traditional western colony and blotting formation assay were utilized XL147 to measure the effects of caffeine in radiation-related apoptosis. All of the data had been examined with a two-tailed Students < 0.05. Outcomes Caffeine suppresses L2AX foci of RT4 cells open to ionizing light < 0.001). 4-Gy IR by itself lead in 24.1 5.0 foci per nucleus compared with 7.9 2.0 foci in the IR and caffeine combinatory treatment (< 0.001). 2-Gy and 4-Gy IR both created a considerably higher strength of L2AX foci in IR by itself treated cells likened to IR plus caffeine treated cells (= 0.047 and = 0.003, respectively) [Figure ?[Body1a1air conditioning unit1c]. Physique 1 Suppressive effects of caffeine on the formation of H2AX foci and 53BP1 foci in ...
Cancer rates were significantly higher in the group of blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the ataxia-telangiectasia gene. The estimated risk of cancer of all types among heterozygotes as compared with noncarriers was 3.8 in men and 3.5 in women, and that for breast cancer in women was 5.1. Among the blood relatives, women with breast cancer were more likely to have been exposed to selected sources of ionizing radiation than controls without cancer (odds ratio = 5.8, P = 0.005). Male and female blood relatives also had 3-fold and 2.6-fold excess mortality from all causes, respectively, from the ages of 20 through 59 years. Conclusions: ...
TY - JOUR. T1 - Myoclonic axial jerks for diagnosing atypical evolution of ataxia telangiectasia. AU - Nakayama, Tojo. AU - Sato, Yuko. AU - Uematsu, Mitsugu. AU - Takagi, Masatoshi. AU - Hasegawa, Setsuko. AU - Kumada, Satoko. AU - Kikuchi, Atsuo. AU - Hino-Fukuyo, Naomi. AU - Sasahara, Yoji. AU - Haginoya, Kazuhiro. AU - Kure, Shigeo. PY - 2015/3/1. Y1 - 2015/3/1. N2 - Background: Ataxia telangiectasia (A-T) is a common inherited cause of early childhood-onset ataxia, distinguished by progressive cerebellum malfunction, capillary vessel extension, and immunodeficiency. The diagnosis of A-T is sometimes difficult to establish in patients with atypical clinical evolution. Case report: We experienced a pediatric 12-years-old female patient, who was finally diagnosed with classic A-T, demonstrating progressive dystonic-myoclonic axial jerks with ataxia as a predominant clinical feature. Oculocutaneous telangiectasias and immune status were unremarkable. Her myoclonic jerks were spontaneous or ...
The Ataxia-telangiectasia mutated (ATM) gene encodes a multifunctional kinase, which is linked to important cellular functions. Women heterozygous for ATM mutations have an estimated relative risk of developing breast cancer of 3.8. However, the pattern of ATM mutations and their role in breast cancer etiology has been controversial and remains unclear. In the present study, we investigated the frequency and spectrum of ATM mutations in a series of sporadic breast cancers and controls from the Brazilian population. Using PCR-Single Strand Conformation Polymorphism (SSCP) analysis and direct DNA sequencing, we screened a panel of 100 consecutive, unselected sporadic breast tumors and 100 matched controls for all 62 coding exons and flanking introns of the ATM gene. Several polymorphisms were detected in 12 of the 62 coding exons of the ATM gene. These polymorphisms were observed in both breast cancer patients and the control population. In addition, evidence of potential ATM mutations was observed in 7
Ataxia Telangiectasia & Immunoglobulin M Decreased Symptom Checker: Possible causes include Ataxia Telangiectasia. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
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Synonyms for Ataxia-telangiectasia in Free Thesaurus. Antonyms for Ataxia-telangiectasia. 3 synonyms for ataxia: ataxy, dyssynergia, motor ataxia. What are synonyms for Ataxia-telangiectasia?
Yosef Shiloh, a David and Inez Myers professor in cancer research at Tel Aviv Universitys Sackler Faculty of Medicine, was selected to receive the 2011 Israel Prize, Israels most distinguished national honor. The prize is awarded by the Israeli Ministry of Education to Israeli citizens who have demonstrated excellence in their chosen profession. Earlier this year Shiloh was the first Israeli to receive the 51st annual G.H.A. Clowes Award from the American Association for Cancer Research. He was honored for his studies on the cellular DNA damage response and the rare genomic instability syndrome ataxia-telangiectasia.. Shiloh has been investigating ataxia-telangiectasia and the defect in the DNA damage response that leads to this disease for more than 30 years. He revolutionized the field when his lab identified the ataxia-telangiectasia gene in 1995 and successfully cloned it, calling it ataxia-telangiectasia mutated. The identification of the ATM gene opened many new avenues of inquiry and ...
Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia A-T Patients Using a LC-MS-Based Label-Free Protein Quantification Technology. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
BackgroundAtaxia telangiectasia (A-T) is a common genetically inherited cause of early childhood-onset ataxia. The infrequency of this disease, vast phenotype variation, disorders with features similar to those of A-T, and lack of definite laboratory test, make diagnosis difficult. In addition, there is no rapid reliable laboratory method for identifying A-T heterozygotes, who susceptible to ionizing radiation (IR), atherosclerosis, diabetes, and cancers. We used SMC1pSer966 (pSMC1) in-cell colorimetric ELISA to diagnosis and screen in A-T families.Materials and Methods: With informed consent, 2cc peripheral blood was collected from the 15 A-T patients, their parents, and 24 healthy controls with no family history of malignancy, diabetes, and atherosclerosis. Extracted peripheral blood mononuclear cells (PBMCs) were cultured in poly-L-Lysine treated 96-well plate with density of 70,000 cells per well. SMC1 phosphorylation was evaluated with cell-based ELISA kit 1 hour after 5 Gy IR and the pSMC1data
In a critical process known as the DNA damage checkpoint, cells monitor their DNA for damage and halt cell division until the damage has been repaired. Kondo et al. (p. 867) now show that two yeast proteins that function in signaling that DNA damage has occurred actually bind close to the site of damage, but do so in distinct ways. They used a chromatin immunoprecipitation method to detect proteins that bound to double-stranded break in the DNA resulting from continuous expression of the HO endonuclease. One of the proteins bound, Mec1, belongs to a family of protein kinases that includes the ATM protein mutated in the human disease ataxia telangiectasia. Another protein bound at the site of damage was Ddc1, itself thought to be a DNA-binding protein that may recruit other proteins to a complex formed at the damage site. Recruitment of Ddc1, but not that of Mec1, required the action of another participant in the checkpoint pathway, called Rad24. The results help clarify how cells recognize ...
Metabolic syndrome is associated with insulin resistance and atherosclerosis. Here, we show that deficiency of one or two alleles of ATM, the protein mutated in the cancer-prone disease ataxia telangiectasia, worsens features of the metabolic syndrome, increases insulin resistance, and accelerates a …
Ravi, Srimadhavi; Barui, Sugata and Kirubakaran, Sivapriya, Targeting the Ataxia Telangiectasia Mutated (ATM) kinase for alleviating cancer, in the 68th Gordon Research Conference for Natural Products and Bioactive Compounds, Proctor Academy, Andover, NH, US, Jul. 28- Aug. 2, 2019 ...
Ataxia Telangiectasia (A-T) - Action for A-T funds high quality peer reviewed medical research to speed up the process of identifying a cure for A-T.
A fact sheet about ataxia telangiectasia (A-T), a rare, recessive genetic disorder of childhood that occurs in between one out of 40,000 and one out of 100,000 persons worldwide.
Falck et al. have made progress in defining the molecular mechanism underlying the S-phase checkpoint activated by ionizing radiation (IR). IR caused rapid, transient degradation of the phosphatase Cdc25A (which dephosphorylates and activates cyclin-dependent kinase 2) in mammalian cells by a mechanism dependent on the catalytic activity and the ability of the kinase Chk2 to interact with and phosphorylate Cdc25A. Furthermore, the degradation of Cdc25A in response to IR occurred in cells with normal and mutated versions of the tumor suppressor p53, confirming the independence of this S-phase checkpoint on the p53 pathway. However, in cells from patients with ataxia telangiectasia with mutations in the ATM gene, Cdc25A persisted after IR, and the cells exhibited radioresistant DNA synthesis. Thus, IR appears to activate a pathway from ATM to Chk2, which then phosphorylates Cdc25A leading to its destruction and a transient block in the progress of the S phase of the cell cycle. J. Falck, N. ...
Ataxia-telangiectasia (AT or A-T), also referred to as ataxia-telangiectasia syndrome or Louis-Bar syndrome, is a rare, neurodegenerative, autosomal recessive disease causing severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease. A-T affects many parts of the body: It impairs certain areas of the brain including the cerebellum, causing difficulty with movement and coordination. It weakens the immune system, causing a predisposition to infection. It prevents repair of broken DNA, increasing the risk of cancer. Symptoms most often first appear in early childhood (the toddler stage) when children begin to walk. Though they usually start walking at a normal age, they wobble or sway when walking, standing still or sitting, and may appear almost as if they are drunk. In late pre-school and early school age, they develop difficulty moving their eyes in a natural manner from one place to the next (oculomotor ...
Ataxia Telangiectasia is a progressive degenerative disease which affects various systems of the body. First signs of the disease usually appear during the second year of life.
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Introduction The ataxia-telangiectasia mutated (ATM) gene (MIM Identification 208900) encodes a proteins kinase Igf1 Everolimus that has a significant function in the activation of cellular replies to DNA double-strand breaks through subsequent phosphorylation of central players in the DNA damage-response pathway. for breasts cancers remain unresolved. SOLUTIONS TO investigate the function of ATM in BC susceptibility we examined 76 uncommon sequence variations in the ATM gene within a case-control family members research of 2 570 situations of breasts cancers and 1 448 handles. The variations had been grouped into three types predicated on their most likely pathogenicity as dependant on in silico evaluation and examined by conditional logistic regression. Most likely pathogenic sequence variations had been genotyped in 129 family of 27 carrier probands (15 which transported c.7271T > G) and improved segregation analysis was utilized to estimation the BC penetrance connected with these uncommon ...
Initial presentation usually is neurologic as evidenced by problems with development of walking, oculomotor abnormalities, and progressive neurologic disability. Risk of recurrent aspiration of oral secretions. In addition to telangiectasia, vitiligo, café-au-lait spots, and premature graying may be present. Absence of secondary sexual characteristics in females. Elevated liver enzymes associated with fatty infiltration of the liver. Ataxia telangiectasia patients are at increased risk for developing malignancies, particularly lymphoma and leukemia in children and gastric carcinoma in adults. Chronic respiratory infections and bronchiectasis, unresponsive to antibiotics, are frequently the ultimate cause of death. Unusual to survive beyond the third decade. ...
The effect of ataxia-telangiectasia mutated kinase-dependent hyperphosphorylation of checkpoint kinase-2 on oligodeoxynucleotide 7909 containing CpG motifs-enhanced sensitivity to X-rays in human lung adenocarcinoma A549 cells Xiaoqun Liu,1,* Xiangdong Liu,2,* Tiankui Qiao,1 Wei Chen,1 Sujuan Yuan1 1Department of Oncology, 2Department of Ophthalmology, Affiliated Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: The aim of the study reported here was to further investigate the potential effect of ataxia-telangiectasia mutated (ATM) kinase-dependent hyperphosphorylation of checkpoint kinase-2 (Chk2) on radiosensitivity enhanced by oligodeoxynucleotide 7909 containing CpG motifs (CpG ODN7909) in human lung adenocarcinoma A549 cells. Methods: In vitro A549 cells were randomly separated into control, CpG, X-ray, CpG+X-ray, ATM kinase-small interfering RNA (siRNA)+CpG+X-ray (ATM-siRNA), and Chk2-siRNA+CpG+X-ray
A coded analysis of X-ray-induced chromatid aberrations in lymphocyte cultures from 45 control individuals and 19 ataxia-telangiectasia (A-T) heterozygotes was performed. The distribution of chromatid breaks induced in the late G2 portion of the cell cycle by 60 cGy of X-rays appeared bimodal in the study population. In six controls (13 percent) and in 12 of 19 (63 percent) A-T heterozygotes, the
Ataxia-Telangiectasia (A-T) is an inherited disease that affects several body systems, including the immune system. People with A-T have an unsteady, wobbly gait (ataxia) that gets worse as they get older; dilated, corkscrew-shaped blood vessels (telangiectasia) on the whites of the eyes and on sun-exposed areas of skin; immunodeficiency involving both humoral (B-lymphocytes) and cellular (T-lymphocytes) immunity; and a high rate of cancer.
Methuselah Co., set up in Yamagata in June 2016, has developed technology to produce autologous fibroblast cells, a cell type which which can be blended with other functional cells to develop regenerative medicine of various types.. BioImpact news release, July 7, 2016. ...
Several immunological abnormalities have been observed in ataxia-telangiectasia (AT), the most consistent being defects of immunoglobulin isotypes, decreased T-cell numbers, and reduced proliferative...
The symptoms of ataxia-telangiectasia (A-T) include a progressive neurodegeneration caused by ATM protein deficiency. The authors previously found that nuclear accumulation of histone deacetylase-4, HDAC4, contributes to this degeneration; they now report that increased trimethylation of histone H3 on Lys27 (H3K27me3) mediated by polycomb repressive complex 2 is also important in the A-T phenotype. [Nat Neurosci ...
An inherited (autosomal recessive) neurological disorder. Ataxia is usually noted early in life, and a key feature is the presence of dilated blood vessels visible in the sclerae of the eyes and on the cheeks and ears. Other symptoms may include slow slurred speech, abnormal eye movements, skin lesions, and immune deficiency. Affected individuals may develop malignant disease. A raised level of alpha-fetoprotein is found in the blood. ...
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Ceralasertib is a potent and selective ATP competitive inhibitor of ataxia telangiectasia and Rad3 related (ATR) in clinical development as monotherapy and in combination with olaparib (Lynparza) and durvalumab (Imfinzi) in patients with advanced solid tumors. Paired pre- and on-treatment tumour samples from seven patients during ceralasertib monotherapy in Phase 1 studies (NCT02223923, NCT02264678), all ATM expressing, showed increases in pRAD50 on treatment. This study aimed to robustly understand the relationship between ceralasertib pharmacokinetics, pRAD50 (pSer635) induction by immunohistochemistry and anti-tumor efficacy, in mouse xenografted models; to enable interpretation of paired clinical tumour samples. First, in vivo data were generated in a range of xenografted models (HBCx9 [TNBC, Xentech], HCC1806 [BC], OCI-Ly19 [DLBCL] and OE21 [HNSCC]) and NSCLC and HNSCC PDX models at Champions). Mouse ceralasertib doses (6.25 - 25mg/kg BID and 50mg/kg QD) reflected the observed free drug ...
TY - JOUR. T1 - Apurinic DNA endonuclease activities in repair-deficient human cell lines. AU - Moses, Robb. AU - Beaudet, Arthur L.. PY - 1978/2. Y1 - 1978/2. N2 - Several autosomal recessive diseases are associated with apparent DNA repair defects in cell culture. It seemed likely that a defect in excision repair reported for ataxia telangiectasia cells might reflect a lack of apurinic endonuclease activity. We report here normal levels of apurinic endonuclease activity in extracts of cell lines derived from patients with ataxia telangiectasia, xeroderma pigmentosum (complementation group D), Cockayne dwarfism, Fanconi anemia and Bloom syndrome.. AB - Several autosomal recessive diseases are associated with apparent DNA repair defects in cell culture. It seemed likely that a defect in excision repair reported for ataxia telangiectasia cells might reflect a lack of apurinic endonuclease activity. We report here normal levels of apurinic endonuclease activity in extracts of cell lines derived ...
TY - JOUR. T1 - Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) protein to regulate intra-S-phase checkpoint. AU - Lee, Alan Yueh Luen. AU - Chiba, Takuya. AU - Truong, Lan N.. AU - Cheng, An Ning. AU - Do, Johnny. AU - Cho, Michael Jeffrey. AU - Chen, Longchuan. AU - Wu, Xiaohua. N1 - Copyright: Copyright 2012 Elsevier B.V., All rights reserved.. PY - 2012/1/20. Y1 - 2012/1/20. N2 - Dbf4/Cdc7 (Dbf4-dependent kinase (DDK)) is activated at the onset of S-phase, and its kinase activity is required for DNA replication initiation from each origin. We showed that DDK is an important target for the S-phase checkpoint in mammalian cells to suppress replication initiation and to protect replication forks. We demonstrated that ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) proteins directly phosphorylate Dbf4 in response to ionizing radiation and replication stress. We identified novel ATM/ATR ...
Salt Lake City - Recursion Pharmaceuticals, an emerging biotech company today announced receipt of a research award from the A-T Childrens Project, which seeks to support research for the disease ataxia-telangiectasia.. Ataxia-telangiectasia (A-T) is a rare genetic disease that attacks children, causing progressive loss of muscle control, immune system problems, and a high rate of cancer. The award will be used to support Recursions efforts to build a many-dimensional cellular model of the disease to be used in future drug screening efforts.. Chris Gibson, Ph.D., CEO of Recursion Pharmaceuticals remarked: We are grateful to the A-T Childrens Project for this award which will enable us to rapidly deploy our innovative drug discovery technology towards Ataxia-telangiectasia. As a young company, the support and trust of foundations like the A-T-Childrens Project is critical to our ability to apply our technology across as many diseases as possible.. Recursions technology, which combines ...
TY - JOUR. T1 - Hodgkin lymphoma in a young child contributing to a diagnosis of ataxia telangiectasia. T2 - Review of the literature. AU - Hummel, Jennifer M.. AU - Thorland, Erik C. AU - Lim, Megan S.. PY - 2010. Y1 - 2010. N2 - Ataxia telangiectasia (A-T) is a rare genetic disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, chromosomal instability, and radiation sensitivity (Peterson et al. Lancet 283:1189-1193, 1964; Boder and Sedgwick Pediatrics 21:526-554, 1958; Taylor et al. Nature 258:427-429, 1975). Compared to the general population, patients with primary immunodeficiencies such as A-T have an increased rate of malignancy and an earlier age at presentation (Loeb et al. J Pediatr Hematol/Oncol 22:464-467, 2000; Taylor et al. Blood 87:423-438, 1996). We report the clinical, histopathologic, and molecular features of a 6-year-old child who presented with EBV-positive Hodgkin lymphoma (HL), which led to the diagnosis of ataxia ...
View more ,Ataxia Telangiectasia is a progressive neurodegenerative disorder caused by mutations in the ataxia telangiectasia mutated (atm) gene. Nuclear ATM has a well established role in response to DNA damage, however ATM has also been localized outside the nucleus where it has been demonstrated to participate in the insulin signalling pathway by phosphorylating eIF-4E binding protein(4EBP1). 4EBP1 is a target of Mammalian target of Rapamycin (mTOR) and its phosphorylation releases it from eIF-4E enabling translation of mRNA and protein synthesis. The Tuberous Sclerosis Complex (TSC) proteins, hamartin (TSC1) and tuberin (TSC2) act as a heterodimer to regulate mTOR activity. mTOR exists as two complexes, mTORC1 (rapamycin sensitive) and mTORC2 (insensitive to short term rapamycin). These complexes control many cellular functions including protein synthesis, autophagy, lipid metabolism, mitochondrial biogenesis and cytoskeletal organisation. Mutations in either of the TSC1 or TSC2 genes lead ...
The kinase ATM is classically known for its role in coordinating the response to DNA damage. DNA damage is caused by various intracellular and extracellular stimuli, including oxidative stress and free radicals. Lee et al. found critical amino acid residues that enable ATM to coordinate a response to DNA damage that is independent of its response to oxidative stress. Activation of ATM by either pathway promoted mitochondrial function and autophagy, thus mediating cell survival through metabolic changes. ATM activation via oxidative stress additionally promoted the clearance of toxic protein aggregates. These findings expand the roles of ATM and suggest that the loss of ATM function, such as in the neurodegenerative disease ataxia telangiectasia (A-T), causes broader cellular stress than that limited to a defective DNA damage response. ...
Minnie Geller Professor. research • lab members • publications. Google Scholar Profile. Representative Publications:. Strand, M., Prolla, T. A., Liskay, R. M. and Petes, T. D. (1993). Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365:274-276.. Fan, Q.-Q., Xu, F. and Petes, T. D. (1995). Meiosis-specific double-strand DNA breaks at the HIS4 recombination hotspot in the yeast Saccharomyces cerevisiae. Mol. Cell. Biol. 15:1679-1688.. Greenwell, P. W., Kronmal, S. L., Porter, S. E., Gassenhuber, J., Obermaier, B., and Petes, T. D. (1995).TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene. Cell 82:823-829.. Kirkpatrick, D. and Petes, T. D. (1997). Repair of DNA loops involves DNA mismatch and nucleotide excision repair proteins. Nature 387:929-931.. Moore, H., Greenwell, P. W., Liu, C.-P., Arnheim, N., and Petes, T. D. (1999). Triplet repeats form secondary ...
Mutations in the ATM gene have previously been identified in CLL tumours. In this project, I have demonstrated that their detection would have prognostic value. With a prevalence of 12%, ATM mutations represent the commonest single gene defect to be detected in CLL tumours and they identified a subgroup of CLL patients that had a significant reduction in both treatment free and overall survival. Furthermore, ATM mutations provided prognostic information that was independent of age, clinical stage, the mutation status of the IGVH genes and TP53 mutations. The temporal acquisition of the ATM mutations and their relationship with loss of an ATM allele via a chromosomal 11q deletion provides clues into their mechanism of action. There was only a partial correlation between CLL tumours with mutations in the ATM gene and those with a chromosome 11q deletion. In certain cases, the ATM mutations represented germ-line changes and in others were acquired very early in the disease course raising the ...
Definition of ataxia telangiectasia syndrome. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.
Ataxia-telangiectasia (A-T) is a rare, autosomal recessive human disorder characterized by cerebellar ataxia, immunodeficiency, cancer predisposition, recurrent...
TOPICS: ATM gene, double-stranded DNA breaks, nonhomologous end joining repair mechanism, cell cycle, mutations, alpha-fetoprotein (AFP), autosomal recessive, cerebellar atrophy, ataxia, spider angiomas (telangiectasias), IgG, radiation, IgA, lymphopenia, lymphoma, leukemia, T cell disorder, B cell disorder, IgE ...
Different excellence centers in Italy and in the world are involved in research projects aimed to define the role of ATM protein in the AT physiopathology the ATM protein. To know the mechanisms that lead to neurodegeneration as a result of the lack of ATM and basilar protein to understand the symptoms of the patients with AT and to propose new therapeutic strategies. ANAT finances for years the following research projects:. In the last years it was proposed that ATM protein is involved in defense mechanisms to oxidative stress and in metabolism.. Projects title: The role of ATM in the control of cellular metabolism Scientific responsible: Doc. Vincenzo Costanzo. Host institute: IFOM, FIRC Institute of Molecular Oncology (Milan). The molecular basis of corticosteroids efficiency in the improvement of neurological symptoms at patients with AT are still research objects.. Project title: Corticosteroids for patients with Ataxia Telangiectasia (AT): the dexamethasone effect on AT cells activity ...
DESCRIPTION (provided by applicant): Ataxia-telangiectasia (A-T) is a multi-systemic, recessively inherited disorder that affects between 1 in 40,000 to 1 in 100,000 individuals worldwide. It is characterized primarily by early onset cerebellar ataxia andtelangiectasia, from which the disease name is derived. In addition, patients also exhibit a number of other clinical symptoms including increased susceptibility to cancer (lymphomas, leukemia, brain tumors), immunodeficiency, insulin-resistant diabetes, chromosomal instability, sensitivity to ionizing radiation, susceptibility to bronchopulmonary disease, and the absence, or almost complete absence, of a thymus. Current treatments for A-T are directed toward the management of symptoms. Physical and speechtherapy can improve the lives of patients, and -globulin injections can be given to support the immune system. However, no treatment is directed at the underlying defect. Consequently, A-T remains a fatal disease. The development of improved ...
We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2 Gy. Tailoring the effective dose through plasma power and duration of the treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei. ...
R. John Davenport http://sageke.sciencemag.org/cgi/content/abstract/sageke;2001/9/nw35 Key Words: genomic instability ATR ATM Ataxia telangiectasia DNA repair double-strand breaks RAD26 DDC2. Abstract: In eukaryotic cells, protein sentries ensure that the genome is complete before cell division proceeds. When DNA is damaged or its replication machinery conks out, the genome guardians attach phosphate groups to other proteins; this chemical addition triggers these proteins to bring the cell cycle to a halt and activate DNA repair machinery. A breakdown in this system can impair health: People with a defective copy of the gene for one of those proteins--called ATM--suffer from a disorder known as ataxia telangiectasia (see Transgenic Mouse Entries: tg1, tg2, and tg3). Symptoms of the disorder include neuronal degeneration, weakened immunity, and increased risk of cancer. Although scientists know a fair amount about ATM, key information is missing about the activities of a related ...
ATM has been shown to have important roles in the transcriptional regulation of gene expression by phosphorylation of transcription factors, such as p53, nuclear factor κB, E2F, cyclic AMP-responsive element binding protein, and BRCA1, and in maintenance of the normal functions of IGF-IR and telomeres (3, 13, 14, 32). ATM-dependent gene expression has been systematically studied by comparing cell lines from normal individuals and AT patients, isogenic cell lines with restoration of ATM in AT cells or small interfering RNA knockdown of ATM in wild-type cells, and ATM+/+/ATM−/− mice (3, 13, 21-23). More than 300 genes have been reported to display ATM-dependent expression although few genes were commonly identified in two or more experiments. The microarray results presented here identified 160 genes or expressed sequence tags (∼1% of the total on the array) that were differentially expressed in normal and AT fibroblast lines under basal growth conditions, of which about half were ...
In previous research, we have demonstrated that tobacco smoke condensate (CSC), a surrogate for tobacco smoke, is with the capacity of changing the spontaneously immortalized human being breasts epithelial cell line, MCF10A. and is recognized as a marker for improved tumor quality 105628-72-6 and nodal metastasis (Olopade gene appearance in MCF10A cellular material. Our results recommend, for the very first time to our understanding, that C/EBP binds the promoter and induces its activity in MCF10A cellular material in response CSC treatment. Outcomes CSC treatment induces bcl-xl mRNA and proteins amounts in MCF10A cellular material To look for the aftereffect of CSC treatment on gene amounts, we treated MCF10A cellular material with increasing levels of CSC for 24 h and mRNA amounts had been assessed by RT-PCR (Fig. 1A). In these cellular material after normalization with mRNA, the mRNA appearance slightly reduces at lower concentrations (2.5 g/mL) and improves at higher concentrations of CSC ...
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Ataxia telangiectasia (A-T) is a rare, recessive, neurodegenerative disease, with symptoms that normally appear in early childhood. Initial indications are usually ataxia (a lack of muscle control leading to loss of balance and coordination) and telangiectasia (tiny red veins, which are most noticeable on the whites of the eyes). The most serious clinical problem is loss of Purkinje cells, leading to degeneration of the cerebellum (the bodys motor control centre). About 70% of sufferers also have thymic hypoplasia and a compromised immune system. Patients are also highly sensitive to X-irradiation and are susceptible to malignant tumors. Currently, there is no cure, nor any treatment that halts the progression of the disease.. A-T is caused by mutation of the ATM gene, which encodes a ubiquitous 370-kD serine-threonine kinase that is essential for normal repair of double-stranded DNA breaks; loss of ATM function results in DNA instability. However, there are atypical cases of A-T in which ATM ...
Introduction Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATMs potential role in resistance to chemotherapy. Methods We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. Results While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% ...
About 1.4% of the general population are heterozygous carriers of the gene for ataxiatelangiectasia (A-T), an autosomal recessive progressive neurologic syndrome in which cancer incidence of homozygotes is approximately 100-fold greater than the general populations rates. The hypothesis that A-T he …
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Ataxia Telangiectasia Mutated protein kinase (ATM) has lately come to the fore as a regulatory protein fulfilling many roles within…. Continue Reading →. ...
Abstract Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the […]. ...
Possibly Dystonia Only Symptom Checker: Possible causes include Ataxia Telangiectasia. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
I was diagnosed with A-T when I was 3 years old. Since 1999, my family and many friends have raised money for the A-T Childrens Project by participating in numerous walks, golf tournaments, and marathons. All of this was done on my behalf. My Pool Challenge is my way of giving back to all our supporters as well as making a difference for A-T people everywhere.. This year I am also walking to honor my dear friend, Kate, who passed early this summer. We met over 12 years ago at an A-T marathon weekend and were fast friends from then on. I know Kate will be cheering for me on July 24. And I will certainly be thinking of her while I walk!. My goal is to raise enough money so the A-T Childrens Project can fund more research to find a cure or treatment for A-T.. ...
Natalie Cole believed blood relatives arent the only ones worthy of being remembered in a will ... she is taking care of 2 friends who took good care of…
Hello, I just found out that I am K01a-T195C! Can anyone explain this classification for me?Am I just K1a or should there be more? What does the T195C! mutation mean?