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ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

GONÇALES Jr.,Fernando Lopes; STUCCHI,Raquel Silveira Bello; PAPAIORDANOU,Priscila Maria Oliveira; PAVAN,Maria Helena Postal; GONÇALES,Neiva Sellan Lopes; PINHO,João Renato Rebello
Fonte: Instituto de Medicina Tropical Publicador: Instituto de Medicina Tropical
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/1998 EN
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The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors...

Grafting amino drugs to poly(styrene-alt-maleic anhydride) as a potential method for drug release

Khazaei,Ardeshir; Saednia,Shahnaz; Saien,Javad; Kazem-Rostami,Masoud; Sadeghpour,Mahdieh; Borazjani,Maryam Kiani; Abbasi,Fatemeh
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2013 EN
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Drug delivery systems based on polymer-drug conjugates give an improved treatment with lower toxicity or side effects and be used for the treatment of different diseases. Conjugates of biodegradable poly(styrene-alt-maleic anhydride) (PSMA), with a therapeutic agents such as amantadine hydrochloride, amlodipine, gabapentin, zonisamide and mesalamine, were afforded by the formation of the amide bonds of the amino drugs that reacted with the PSMA anhydride groups. The amounts of covalently conjugated drugs were determined by a¹ H NMR spectroscopic method, and the in vitro release rate in buffer solution (pH 1.3) was studied at body temperature 37 ºC. In kinetic studies, different dissolution models were examined to obtain drug release data and the collected data were well-fitted to the Korsmeyer-Peppas equation, revealing a dominant Fickian diffusion mechanism for drug release under the in vitro conditions.

Liver histological alterations in patients with chronic hepatitis C and normal ALT levels in the city of Salvador, Northeast-Brazil

Santana,Nelma Pereira de; Freitas,Luiz A.R. de; Lyra,André Castro; Paraná,Raymundo; Santana,Genoile; Trepo,Christian; Lyra,Luiz G.C.
Fonte: Brazilian Society of Infectious Diseases Publicador: Brazilian Society of Infectious Diseases
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2005 EN
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Patients with chronic hepatitis C can have variable clinical progression. Hepatic histological alterations appear to be milder in asymptomatic subjects who have persistently normal ALT levels. AIMS: To evaluate the severity of histological liver alterations in blood donors with normal and elevated ALT levels. METHODS: We evaluated volunteer blood donors from the main blood bank of the city of Salvador-Brazil. Those who were anti-HCV positive were invited to participate in the study. Serum ALT and AST levels were measured at two time points, two months apart. Donors were divided into two groups: group I, individuals with ALT > 1.5 times the upper limit of normal in at least one time point and group II, individuals with normal or near normal ALT, at both time points RESULTS: We evaluated 30,232 blood donors and 528 (1.7%) of them were anti-HCV positive. Eighty-two attended our service and HCV infection was confirmed in 66 individuals. Male gender predominated in both groups; the mean age was 36 for group I, and 33 for group II. Tattoos and intravenous illicit drug use were frequently-encountered risk factors. Liver biopsy was done in 43 subjects. Among donors with elevated ALT, two (10%) had minimum alterations, while in group II normal liver or minimum alterations were observed in six (26%) subjects. Chronic hepatitis or cirrhosis was encountered in 35 (81%) individuals: three (15%) and five (21%) subjects had chronic hepatitis without inflammatory activity...

ALT-C, a disintegrin-like Cys-rich protein from Bothrops alternatus, increases skeletal myoblast viability

Mesquita-Ferrari,RA; Moraes,CK de; Micocci,KC; Selistre-de-Araújo,HS
Fonte: Centro de Estudos de Venenos e Animais Peçonhentos - CEVAP, Universidade Estadual Paulista - UNESP Publicador: Centro de Estudos de Venenos e Animais Peçonhentos - CEVAP, Universidade Estadual Paulista - UNESP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2009 EN
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ALT-C, an ECD motif (glutamic acid, cysteine, aspartic acid) disintegrin from Bothrops alternatus snake venom, induces α2β1 integrin-mediated signaling and neutrophil chemotaxis. In vitro, in human umbilical vein endothelial cells (HUVEC), ALT-C induces cell proliferation, thus showing an interesting potential for tissue regeneration studies. This work aimed to evaluate the influence of ALT-C in myoblast viability and differentiation. Myoblasts were obtained from hind limb muscles of 3 to 4-day old Wistar rats. The cells were incubated with ALT-C at different concentrations and incubation periods were followed by total RNA isolation. cDNA synthesis and real time polymerase chain reaction (PCR) were performed with primers of myoD as well as of both (slow and fast) myosin heavy chain isoforms (MHC). ECD-disintegrin increased myoblast viability in a dose-dependent way, mostly with 50 to 100 nM concentrations, and such effect was more prevalent after 48 hours. No changes in gene expression of both MHC isoforms were observed in ALT-C-treated cells. MyoD expression was not detected, which suggests that myoblasts were in mature stages. Protease activity and cytokine array tested in a medium of 50 nM ALT-C-treated cells after 48 hours were not different from controls. In conclusion...

Cloning of a Gene Encoding an Alt a 1 Isoallergen Differentially Expressed by the Necrotrophic Fungus Alternaria brassicicola during Arabidopsis Infection

Cramer, Robert A.; Lawrence, Christopher B.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/2003 EN
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Alternaria species are considered some of the most important fungi responsible for allergenic morbidity in humans. The Alternaria protein that elicits the most intense allergic reaction in humans is Alt a 1, yet no biological function has been identified for this protein. In this study, suppression subtractive hybridization and virtual Northern blots were used to identify and characterize an Alt a 1 homolog in the phytopathogenic fungus Alternaria brassicicola. RNA was extracted from A. brassicicola spores germinated in water and on leaf surfaces of the Arabidopsis ecotype Landsberg for 24 h and used to create cDNA by PCR. Double-stranded cDNA was then used in suppression subtractive hybridization to identify differentially expressed genes. mRNA transcript levels were assessed by virtual Northern blotting. A sequence with significant homology (90% amino acid, 92% cDNA) to the Alt a 1 subunit from Alternaria alternata was identified. Virtual Northern blots demonstrated that this homolog, designated Alt b 1 precursor, was highly up-regulated during the infection process of A. brassicicola on Arabidopsis. The full-length cDNA sequence of Alt b 1 was 815 bp, with an open reading frame of 477 bp. In this preliminary study, we identified a homolog of the major Alternaria allergen precursor...

High level of telomerase RNA gene expression is associated with chromatin modification, the ALT phenotype and poor prognosis in liposarcoma

Cairney, C J; Hoare, S F; Daidone, M-G; Zaffaroni, N; Keith, W N
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
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Telomere length is maintained by two known mechanisms, activation of telomerase or alternative lengthening of telomeres (ALT). The ALT pathway is more commonly activated in tumours of mesenchymal origin, although the mechanisms involved in the decision of a cell to activate either telomerase or ALT are unknown at present and no molecular markers exist to define the ALT phenotype. We have previously shown an association between chromatin remodelling, telomerase gene expression and ALT in cell line models. Here, we evaluate these findings and investigate their prognostic significance in a panel of liposarcoma tissue samples to understand the biology underlying the ALT phenotype. Liposarcoma samples were split into three groups: telomerase positive (Tel+); ALT positive; ALT−/Tel−. Differences in telomerase gene expression were evident between the groups with increased expression of hTR in ALT and Tel+ compared to ALT−/Tel− samples and increased hTERT in Tel+ samples only. Investigation of a small panel of chromatin modifications revealed significantly increased binding of acetyl H3 in association with hTR expression. We confirm that the presence of the ALT phenotype is associated with poor prognosis and in addition, for the first time...

A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT

Lafferty-Whyte, Kyle; Cairney, Claire J.; Will, Malcolm B.; Serakinci, Nedime; Daidone, Maria-Grazia; Zaffaroni, Nadia; Bilsland, Alan; Keith, W. Nicol
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Telomere length is maintained by 2 known mechanisms, activation of telomerase or alternative lengthening of telomeres (ALT). The molecular mechanisms regulating the ALT phenotype are poorly understood and it is unknown how the decision of which pathway to activate is made at the cellular level. We have shown previously that active repression of telomerase gene expression by chromatin remodelling of the promoters is one mechanism of regulation, however other genes and signalling networks are likely to be required to regulate telomerase and maintain the ALT phenotype. Using gene expression profiling we have uncovered a signature of 1305 genes to distinguish telomerase positive and ALT cell lines. By combining this with gene expression profiles of liposarcoma tissue samples we refined this signature to 297 genes. Network analysis of known interactions between genes within this signature revealed a regulatory signalling network consistent with a model of hTERT repression in ALT cell lines and liposarcomas. This network expands on our existing knowledge of hTERT regulation and provides a platform to understand differential regulation of hTERT in different tumour types and normal tissues. We also show evidence to suggest a novel mesenchymal stem cell origin for ALT immortalisation in cell lines and mesenchymal tissues.

Factors underlying the association of body mass index with serum ALT in Chinese hypertensive adults without known hepatic diseases*

Zhang, Yan; Qin, Xian-hui; Li, Jian-ping; Cui, Yi-min; Liu, Ze-yuan; Zhao, Zhi-gang; Ge, Jun-bo; Guan, De-ming; Hu, Jian; Wang, Yan-ni; Zhang, Fu-min; Xu, Xin; Xu, Xi-ping; Huo, Yong
Fonte: Zhejiang University Press Publicador: Zhejiang University Press
Tipo: Artigo de Revista Científica
Publicado em /08/2013 EN
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Objective: High body mass index (BMI) is considered as the most important risk factor for elevated serum alanine aminotransferase (ALT) concentration. This study examined an array of factors, including waist circumference (WC) and folate deficiency, which may mediate the association of BMI with serum ALT concentration in Chinese hypertensive adults without known hepatic diseases. Methods: A multicenter, cross-sectional study was carried out. A total of 378 patients with mild or moderate hypertension and without known hepatic diseases were recruited from five hospitals in Harbin, Shanghai, Beijing, Xi’an, and Nanjing. Results: Of the 360 hypertensive patients with complete data in our final analysis, 13.6% had high ALT concentrations (>40 IU/L). Factors including BMI, WC, triglyceride level, and folate concentration were associated with ALT concentration in univariate analysis. Consistently higher prevalence rates of elevated ALT were observed in subjects with lower folate concentrations (≥12 vs. <12 nmol/L, 9.9% vs. 17.8%, P=0.03), with higher BMI (≥28 vs. <28 kg/m2, 21.5% vs. 11.4%, P=0.02) or higher WC (≥90 vs. <90 cm, 18.5% vs. 10.0%, P=0.02). However, in multivariate analysis, the association between BMI and ALT concentration disappeared (P=0.802 in males and 0.369 in females)...

The telomere-associated homeobox-containing protein TAH1/HMBOX1 participates in telomere maintenance in ALT cells

Feng, Xuyang; Luo, Zhenhua; Jiang, Shuai; Li, Feng; Han, Xin; Hu, Yang; Wang, Dan; Zhao, Yong; Ma, Wenbin; Liu, Dan; Huang, Junjiu; Songyang, Zhou
Fonte: The Company of Biologists Publicador: The Company of Biologists
Tipo: Artigo de Revista Científica
Publicado em 01/09/2013 EN
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The majority of cancer cells rely on elevated telomerase expression and activity for rapid growth and proliferation. Telomerase-negative cancer cells, by contrast, often employ the alternative lengthening of telomeres (ALT) pathway to maintain telomeres. ALT cells are characterized by long and dynamic telomeres and the presence of ALT-associated promyelocytic leukemia (PML) bodies (APBs). Previous work has shown the importance of APBs to the ALT pathway, but their formation and precise role remain unclear. Here, we demonstrate that a homeobox-containing protein known as HMBOX1 can directly bind telomeric double-stranded DNA and associate with PML nuclear bodies. Hence, we renamed this protein TAH1 for telomere-associated homeobox-containing protein 1. TAH1 knockdown significantly reduced the number of APBs and led to an increase in DNA damage response signals at telomeres. Importantly, TAH1 inhibition also notably reduced the presence of telomere C-circles, indicating altered ALT activity. Our findings point to TAH1 as a novel link between pathways that regulate DNA damage responses, PML nuclear bodies, and telomere homeostasis in ALT cells, and provide insight into how ALT cells may achieve sustained growth and proliferation independent of the telomerase.

The Genetic Architecture of Liver Enzyme Levels: GGT, ALT and AST

van Beek, Jenny H. D. A.; de Moor, Marleen H. M.; de Geus, Eco J. C.; Lubke, Gitta H.; Vink, Jacqueline M.; Willemsen, Gonneke; Boomsma, Dorret I.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were assessed in a large sample of twins, their siblings, parents and spouses (N = 8,371; age range 18–90). For GGT and ALT, but not for AST, genetic structural equation modeling showed evidence for quantitative sex differences in the genetic architecture. There was no evidence for qualitative sex differences, i.e. the same genes were expressed in males and females. Both additive and non-additive genetic factors were important for GGT in females (total heritability h2 60 %) and AST in both sexes (total h2 43 %). The heritability of GGT in males and ALT for both sexes was due to additive effects only (GGT males 30 %; ALT males 40 %, females 22 %). Evidence emerged for shared environmental factors influencing GGT in the male offspring generation (variance explained 28 %). Thus...

RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells

Arora, Rajika; Lee, Yongwoo; Wischnewski, Harry; Brun, Catherine M.; Schwarz, Tobias; Azzalin, Claus M.
Fonte: Nature Pub. Group Publicador: Nature Pub. Group
Tipo: Artigo de Revista Científica
Publicado em 21/10/2014 EN
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A fraction of cancer cells maintain telomeres through the telomerase-independent, ‘Alternative Lengthening of Telomeres’ (ALT) pathway. ALT relies on homologous recombination (HR) between telomeric sequences; yet, what makes ALT telomeres recombinogenic remains unclear. Here we show that the RNA endonuclease RNaseH1 regulates the levels of RNA–DNA hybrids between telomeric DNA and the long noncoding RNA TERRA, and is a key mediator of telomere maintenance in ALT cells. RNaseH1 associated to telomeres specifically in ALT cells and its depletion led to telomeric hybrid accumulation, exposure of single-stranded telomeric DNA, activation of replication protein A at telomeres and abrupt telomere excision. Conversely, overexpression of RNaseH1 weakened the recombinogenic nature of ALT telomeres and led to telomere shortening. Altering cellular RNaseH1 levels did not perturb telomere homoeostasis in telomerase-positive cells. RNaseH1 maintains regulated levels of telomeric RNA–DNA hybrids at ALT telomeres to trigger HR without compromising telomere integrity too severely.

Production of the Allergenic Protein Alt a 1 by Alternaria Isolates from Working Environments

Skóra, Justyna; Otlewska, Anna; Gutarowska, Beata; Leszczyńska, Joanna; Majak, Iwona; Stępień, Łukasz
Fonte: MDPI Publicador: MDPI
Tipo: Artigo de Revista Científica
EN
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The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather) present within the working environment stimulate or inhibit Alt a 1 production (ELISA test). Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%–16% frequency in the air). The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103–6.528 ng/mL) than a ATCC strain (0.551–0.975 ng/mL). It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein.

Metabolic Adaptive ALT Isoenzyme Response in Livers of C57/BL6 Mice Treated with Dexamethasone

Reagan, William J.; Yang, Rong-Ze; Park, Soohyun; Goldstein, Richard; Brees, Dominique; Gong, Da-wei
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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27.13%
Alanine aminotransferase (ALT) is used as an indicator of hepatocellular injury. Since ALT consists of two isoenzymes, a better understanding of ALT isoenzyme biology in response to compounds that cause metabolic adaptive versus hepatotoxic responses will allow for a more accurate assessment of the significance of an ALT increase. The purpose of this study was to characterize the ALT isoenzyme response in mice treated with 25 or 75 mg/kg of dexamethasone, which is known to induce a progluconeogenic state, for 24 or 72 hr. Those mice treated with 75 mg/kg for 72 hr showed an increase in total liver ALT activity. Western blot showed that there was an increase in ALT2 at both doses and time points and there was a concurrent increase in ALT2 ribonucleic acid at 24 and 72 hr. The ALT isoenzyme response assessed by an activity assay showed an increase in ALT2. The increases in liver ALT were associated with an increase in liver glycogen and there was no hepatocellular necrosis. There was an increase in total serum ALT activity, although serum isoenzymes were not evaluated. Thus, the authors demonstrated that dexamethasone induced increases in hepatic and serum ALT, which reflect a hepatocellular progluconeogenic metabolic adaptive response.

Quality of life in HCV-infection: lack of association with ALT levels

Miller, E.; Hiller, J.
Fonte: Public Health Assoc Australia Inc Publicador: Public Health Assoc Australia Inc
Tipo: Artigo de Revista Científica
Publicado em //2001 EN
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Objectives: To examine the impact of HCV infection in an Australian clinic population and identify the relationships between morbidity, psychosocial variables and one clinical indicator of HCV activity, alanine aminotransferase (ALT). Method: Ninety-five untreated HCV-infected patients (21-69 years) in infectious and liver diseases clinics who were all positive for HCV-RNA and had no significant comorbidities or coinfections completed a survey containing the Short Form 36 (SF36), as well as the six-item Social Support Questionnaire (SSQ6), demographic items and questions concerning respondents’ perceptions of their mode and duration of infection. Nine volunteers from this group participated in semi-structured qualitative interviews aimed at exploring the social impact of HCV status. These data were compared with serum ALT levels. SF36 scores were compared to population norms and according to participant variables. Results: Mean SF36 scores were significantly lower, across all modalities, than population norms. SF36 scores differed significantly according to age, sex, mode of infection, alcohol and methadone use, and satisfaction with social support. They did not differ significantly according to perceived or actual ALT level or pattern of ALT activity. Worry about ALT was prevalent (>50%) and this was independent of perceived ALT level. Conclusions and implications: HCVinfection is associated with significantly reduced quality of life and includes the perception of substantial social discrimination. ALT levels are of limited usefulness in ascertainment of a person’s sense of wellbeing and quality of life in HCV-infection. Increased support and information for affected individuals and measures aimed at countering social discrimination are important recommendations of the current study.; Emma R. Miller...

Lack of TRF2 in ALT cells causes PML-dependent p53 activation and loss of telomeric DNA

Stagno D'Alcontres, Martina; Mendez-Bermudez, Aaron; Foxon, Jennifer L.; Royle, Nicola J.; Salomoni, Paolo
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 03/12/2007 EN
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Alternative lengthening of telomere (ALT) tumors maintain telomeres by a telomerase-independent mechanism and are characterized by a nuclear structure called the ALT-associated PML body (APB). TRF2 is a component of a telomeric DNA/protein complex called shelterin. However, TRF2 function in ALT cells remains elusive. In telomerase-positive tumor cells, TRF2 inactivation results in telomere de-protection, activation of ATM, and consequent induction of p53-dependent apoptosis. We show that in ALT cells this sequence of events is different. First, TRF2 inactivation/silencing does not induce cell death in p53-proficient ALT cells, but rather triggers cellular senescence. Second, ATM is constitutively activated in ALT cells and colocalizes with TRF2 into APBs. However, it is only following TRF2 silencing that the ATM target p53 is activated. In this context, PML is indispensable for p53-dependent p21 induction. Finally, we find a substantial loss of telomeric DNA upon stable TRF2 knockdown in ALT cells. Overall, we provide insight into the functional consequences of shelterin alterations in ALT cells.

Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient Ustilago maydis

Yu, Eun Young; Pérez-Martín, José; Holloman, William K.; Lue, Neal F.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 22/10/2015 EN
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A subset of human cancer cells uses a specialized, aberrant recombination pathway known as ALT to maintain telomeres, which in these cells are characterized by complex aberrations including length heterogeneity, high levels of unpaired C-strand, and accumulation of extra-chromosomal telomere repeats (ECTR). These phenotypes have not been recapitulated in any standard budding or fission yeast mutant. We found that eliminating Ku70 or Ku80 in the yeast-like fungus Ustilago maydis results initially in all the characteristic telomere aberrations of ALT cancer cells, including C-circles, a highly specific marker of ALT. Subsequently the ku mutants experience permanent G2 cell cycle arrest, accompanied by loss of telomere repeats from chromosome ends and even more drastic accumulation of very short ECTRs (vsECTRs). The deletion of atr1 or chk1 rescued the lethality of the ku mutant, and “trapped” the telomere aberrations in the early ALT-like stage. Telomere abnormalities are telomerase-independent, but dramatically suppressed by deletion of mre11 or blm, suggesting major roles for these factors in the induction of the ALT pathway. In contrast, removal of other DNA damage response and repair factors such as Rad51 has disparate effects on the ALT phenotypes...

Association of BLM and BRCA1 during Telomere Maintenance in ALT Cells

Acharya, Samir; Kaul, Zeenia; Gocha, April Sandy; Martinez, Alaina R.; Harris, Julia; Parvin, Jeffrey D.; Groden, Joanna
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 01/08/2014 EN
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Fifteen percent of tumors utilize recombination-based alternative lengthening of telomeres (ALT) to maintain telomeres. The mechanisms underlying ALT are unclear but involve several proteins involved in homologous recombination including the BLM helicase, mutated in Bloom's syndrome, and the BRCA1 tumor suppressor. Cells deficient in either BLM or BRCA1 have phenotypes consistent with telomere dysfunction. Although BLM associates with numerous DNA damage repair proteins including BRCA1 during DNA repair, the functional consequences of BLM-BRCA1 association in telomere maintenance are not completely understood. Our earlier work showed the involvement of BRCA1 in different mechanisms of ALT, and telomere shortening upon loss of BLM in ALT cells. In order to delineate their roles in telomere maintenance, we studied their association in telomere metabolism in cells using ALT. This work shows that BLM and BRCA1 co-localize with RAD50 at telomeres during S- and G2-phases of the cell cycle in immortalized human cells using ALT but not in cells using telomerase to maintain telomeres. Co-immunoprecipitation of BRCA1 and BLM is enhanced in ALT cells at G2. Furthermore, BRCA1 and BLM interact with RAD50 predominantly in S- and G2-phases, respectively. Biochemical assays demonstrate that full-length BRCA1 increases the unwinding rate of BLM three-fold in assays using a DNA substrate that models a forked structure composed of telomeric repeats. Our results suggest that BRCA1 participates in ALT through its interactions with RAD50 and BLM.

Comparison of Histologic Characteristics of Chinese Chronic Hepatitis B Patients with Persistently Normal or Mildly Elevated ALT

Wang, Hong; Xue, Li; Yan, Rong; Zhou, Yin; Wang, Ming-Shan; Cheng, Mei-Juan; Hai-Jun Huang,
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 18/11/2013 EN
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27.18%
Liver disease can develop in chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT) who seldom undergo liver biopsy. We aimed to determine histologic characteristics of a large cohort of Chinese CHB patients undergoing liver biopsy and to evaluate the utility of ALT and HBV DNA values at the time of biopsy in predicting liver disease in this population. This prospective study enrolled 230 treatment-naïve patients with persistently normal or mildly elevated ALT. All patients had a liver biopsy. ALT, aspartate aminotransferase (AST), and HBV DNA levels were some of the other parameters measured. Using Scheuer's classification, significant histology was defined as stage ≧2 fibrosis and/or stage 1 fibrosis plus≧ grade 2 inflammation. Liver disease was observed in 34.4% and 61.8% of patients with normal ALT and mildly elevated ALT, respectively. Patients with mildly elevated ALT levels had significantly more events, including liver disease, elevated AST, and moderate to severe inflammation and liver fibrosis, than patients with normal ALT (all P≤0.005). A total of 107 patients (46.5%) had liver disease and 123 (53.5%) did not. PLT and ALT were significantly associated with liver disease (both P<0.001). Patients with elevated ALT...

Los cambios en la tipología de los asentamientos : El caso de la llanura del Alt Empordà (Girona)

Cuadrado Ciuraneta, Sergi; Durà Guimerà, Antoni; Estalella Boadella, Helena
Fonte: Universidade Autônoma de Barcelona Publicador: Universidade Autônoma de Barcelona
Tipo: Artigo de Revista Científica Formato: application/pdf; application/pdf
Publicado em //2007 SPA
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El articulo presenta los principales resultados de una investigación en la que se han examinado los cambios en la tipología de los asentamientos en la llanura del Alt Empordà (Girona). Así, además de una reflexión teórica realizada a partir de la literatura existente, se analiza la situación de los asentamientos en los años cincuenta y a finales del siglo XX a partir de la construcción y la posterior aplicación de una tipología de los asentamientos. Posteriormente, se consideran los procesos que actualmente los están transformando y redefiniendo

Long term follow-up and patterns of response of ALT in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha; Seguimento tardio e padrões de resposta da ALT em pacientes com hepatite crônica NANB/C tratados com interferon-alfa

Silva, L.C. da; Ono, S.K.; Fonseca, L.E.P.; Carrilho, F.J.; Mendes, L.C.A.; França, A.V.C.; Madruga, C.L.A.; Laudanna, A.A.
Fonte: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo Publicador: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; ; Formato: application/pdf
Publicado em 01/06/1995 ENG
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A resposta ao tratamento com interferon em pacientes com hepatite crônica NANB/C tem sido classificada como completa, parcial ou ausente, de acordo com o comportamento da alanino aminotransferase sérica (ALT). Entretanto, uma observação mais detalhada da atividade enzimática tem mostrado que os padrões podem ser mais complexos. O objetivo deste estudo foi descrever o seguimento tardio e os padrões de resposta da ALT em pacientes com hepatite crônica NANB/C tratados com interferon alfa recombinante. Classificamos os tipos de resposta da ALT em 6 padrões e as freqüências observadas foram:I. Resposta completa e persistente = 9 (20,5%); II. Resposta completa com recaída persistente após o IFN = 7 (15,9%); III. Resposta completa com recaída temporária = 5 (11,9%); IV. Normalização temporária e recaída durante o tratamento com IFN = 4 (9,1%); V. Resposta parcial (queda dos níveis iniciais da ALT maior que 50%) = 7 (15,9%); VI. Não resposta = 12 (27,3%). Em conclusão, os padrões de ALT variam durante e após o tratamento e podem ser classificados em pelo menos 6 tipos.; The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as complete, partial or absent, according to the behavior of serum alanine aminotransferase (ALT). However...