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Consistent Alterations of Circulating Matrix Metalloproteinases Levels in Untreated Hypertensives and in Spontaneously Hypertensive Rats: A Relevant Pharmacological Target

FONTANA, Vanessa; SILVA, Pamela S.; BELO, Vanessa A.; ANTONIO, Raquel C.; CERON, Carla S.; BIAGI, Celso; GERLACH, Raquel F.; TANUS-SANTOS, Jose E.
Fonte: WILEY-BLACKWELL Publicador: WILEY-BLACKWELL
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
18.23%
Inconsistent matrix metalloproteinases (MMPs) levels have been reported in hypertension, with higher, similar and lower MMPs levels reported in hypertensives compared with normotensives. Differences between studies may reflect lack of control of drug effects, accompanying diseases and pre-analytical issues. We compared MMP-2, MMP-8 and MMP-9 levels in 38 untreated hypertensive patients (with no other diseases) with those found in 33 normotensive controls. We also studied endogenous MMPs inhibitors (TIMP-1, TIMP-2 and alpha-2-macroglobulin-A2M). Additionally, we assessed MMPs and A2M levels in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. We hypothesized that similar MMPs/endogenous inhibitors` profiles would be found in this animal model of hypertension and in clinical hypertension. MMPs, TIMPs and A2M were measured in plasma samples with commercially available ELISA and gelatin zymography. We found unaltered MMP-2, MMP-8, TIMP-1, TIMP-2 and A2M levels in hypertension. However, hypertensives had higher MMP-9 levels and MMP-9/A2M ratios than normotensives. Moreover, while we found similar MMP-2 and A2M levels in SHR and WKY rats, we found higher MMP-9 levels and MMP-9/A2M ratios in SHR versus WKY rats. These findings show consistent abnormal net plasma MMP-9 (but not MMP-2) activity in clinical and experimental hypertension. These parallel alterations in clinical hypertension and in SHR suggest an important role for MMPs in hypertension. While MMPs may be a relevant pharmacological target...

Polimorfismos nos genes DGAT-1 e A2M e suas associações com produção e qualidade do leite de búfalas da raça Murrah

Freitas, Ana Cláudia de
Fonte: Universidade Estadual Paulista (UNESP) Publicador: Universidade Estadual Paulista (UNESP)
Tipo: Dissertação de Mestrado Formato: x, 35 p.
POR
Relevância na Pesquisa
28.05%
Pós-graduação em Genética e Melhoramento Animal - FCAV; The search for genes that affect milk yield and composition traits has been the aim of many studies in recent years, as the case of candidate gene DGAT1, admittedly involved with the fat content in milk being of great interest to breeders of dairy herds. Another important gene, A2M, has association with cellular processes of the immune system, such as somatic cell count (SCC), directly linked to milk quality and animal health. The aim of the present study was to verify the existence of polymorphisms in this two genes and their effects in composition and milk yield traits in breed buffaloes (Bubalus bubalis). The sample was constituted by 200 buffaloes cows. Hair were used for the extraction of DNA. After PCR, the samples were analyzed by sequencing techniques. Were found six SNPs, but only three in the coding region, two in exon 17 of the DGAT1 gene (SNP 162G/A and 164C/T) and one in exon 29 of the gene A2M (SNP 241A/G ). The SNP 164C/T was associated with the characteristics fat percentage and protein percentage in milk at 5% significance, since the SNP 241A/G besides having association with the same characteristics, also presented with the characteristic fat production. Before addition...

Consistent Alterations of Circulating Matrix Metalloproteinases Levels in Untreated Hypertensives and in Spontaneously Hypertensive Rats: A Relevant Pharmacological Target

FONTANA, Vanessa; SILVA, Pamela S.; BELO, Vanessa A.; ANTONIO, Raquel C.; CERON, Carla S.; BIAGI, Celso; GERLACH, Raquel F.; TANUS-SANTOS, Jose E.
Fonte: WILEY-BLACKWELL Publicador: WILEY-BLACKWELL
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
18.23%
Inconsistent matrix metalloproteinases (MMPs) levels have been reported in hypertension, with higher, similar and lower MMPs levels reported in hypertensives compared with normotensives. Differences between studies may reflect lack of control of drug effects, accompanying diseases and pre-analytical issues. We compared MMP-2, MMP-8 and MMP-9 levels in 38 untreated hypertensive patients (with no other diseases) with those found in 33 normotensive controls. We also studied endogenous MMPs inhibitors (TIMP-1, TIMP-2 and alpha-2-macroglobulin-A2M). Additionally, we assessed MMPs and A2M levels in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. We hypothesized that similar MMPs/endogenous inhibitors` profiles would be found in this animal model of hypertension and in clinical hypertension. MMPs, TIMPs and A2M were measured in plasma samples with commercially available ELISA and gelatin zymography. We found unaltered MMP-2, MMP-8, TIMP-1, TIMP-2 and A2M levels in hypertension. However, hypertensives had higher MMP-9 levels and MMP-9/A2M ratios than normotensives. Moreover, while we found similar MMP-2 and A2M levels in SHR and WKY rats, we found higher MMP-9 levels and MMP-9/A2M ratios in SHR versus WKY rats. These findings show consistent abnormal net plasma MMP-9 (but not MMP-2) activity in clinical and experimental hypertension. These parallel alterations in clinical hypertension and in SHR suggest an important role for MMPs in hypertension. While MMPs may be a relevant pharmacological target...

Estudo in silico de mecanismos moleculares da coagulação / fibrinólise envolvidos no processo de cicatrização na diabetes Mellitus tipo 2 - implicações na saúde oral

Amaral, Diana Isabel
Fonte: Universidade Católica Portuguesa Publicador: Universidade Católica Portuguesa
Tipo: Dissertação de Mestrado
Publicado em 10/10/2011 POR
Relevância na Pesquisa
27.36%
Com o desenvolvimento da investigação biomédica e de novas metodologias da Proteómica, foi possível identificar a totalidade de proteínas presentes em células individuais, tecidos e órgãos e relacionar com algumas patologias as alterações destas proteínas nomeadamente a sua presença, ausência, modificações pós-tradução ou quantidade expressa. Para analisar o elevado número de proteínas identificadas em proteomas é necessário recorrer à utilização de ferramentas bioinformáticas para que seja possível integrar a informação obtida e comparar com a informação disponível em diferentes bases de dados. As abordagens referidas são hoje um contributo decisivo para o esclarecimento de mecanismos moleculares e fisiopatológicos. A Diabetes mellitus tipo 2 (DMT2), por ser uma patologia de etiologia multifactorial prevalente e com implicações relevantes na cavidade oral, principalmente pela dificuldade acrescida de cicatrização, constitui-se como um bom modelo de estudo para a aplicação da Bioinformática Médica à Medicina Dentária. O presente trabalho é dedicado à análise dos proteoma salivar resultante da DMT2 no sentido de verificar a presença, na saliva, de proteínas alteradas envolvidas na coagulação sanguínea e fibrinólise...

An inhibition ELISA to determine alpha macroglobulin levels in mouse plasma

Luz,Mauricio R. M. P.; Van Leuven,Fredt; Jorge,Tania C. Araujo
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/1994 EN
Relevância na Pesquisa
27.36%
A sensitive method for quantifying mouse plasma alpha-macroglobulins (AM) using an inhibition ELISA is described. AM are important plasmaproteinase inhibitors that possibly act also as immunomodulatory molecules. The standard protocol develope in our experiments involves coating well with 10 µg/ml A2M in carbonate buffer, followed by incubation with a 1:1 (v/v) mixture of the plasma to be tested (diluted 1/1000) and goat anti-AM (diluted 1/1250). This is followed by further incubation, first with the enzyme-conjugated antibody and with the substrate prior to the reading of absorbance levels of the reaction products. Standard curve samples must be included in each plate, employing known amounts of the purified Murine Alpha-2-Macroglobulin (MuA2M) used for coating, with concentrations ranging from 0.001 to 10 µg/ml. Using test samples in triplicates and a 6-point standard curve in a single ELISA plate, 25 plasma samples can be tested accurately. The method offers an useful tool for establishing AM levelsin small samples of mouse plasma.

Structure of the A2m(1) allotype of human IgA—a recombinant molecule

Tsuzukida, Yasuharu; Wang, Chi-Chin; Putnam, Frank W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1979 EN
Relevância na Pesquisa
28.33%
The complete amino-acid sequence of the constant (C) region of the α2 heavy chain of a human IgA2 protein of the A2m(1) allotype has been determined. Excluding the hinge region and the carbohydrate content, this α2 allotype differs from the α1 chain in only 14 amino-acid positions; all of these are identical to the A2m(2) allotype of the α2 chain and confer subclass (or isotypic) character on the α2 chains. However, the A2m(2) allotype differs in six positions where A2m(1) and α1 are identical; the first two are just before the hinge and the other four are in the last (CH3) domain. The A2m allotypic character of α2 chains is attributed to several conformational factors in the sequence at positions 211-221, just before the hinge. The isoallotypic determinant shared by α1 chains and the A2m(1) allotype of α2 resides in the identity of their CH3 domains. Thus, the A2m(1) allotype appears to be a hybrid chain that is identical with α1 in the CH3 domain and identical with the A2m(2) α2 chain in the CH1 and CH2 domains and in the hinge, except for the allotypic determinants arising from four structural differences from residues 211-221. The genetic origin of isotypes, allotypes, and isoallotypes of the α chain has involved several events of homologous crossing over and neutral point mutations accumulated late in the evolutionary development of IgA immunoglobulins. Since the crossing over appears to occur between CH2 and CH3...

Complete amino acid sequence of the alpha 2 heavy chain of a human IgA2 immunoglobulin of the A2m (2) allotype.

Toraño, A; Putnam, F W
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1978 EN
Relevância na Pesquisa
27.36%
The complete amino acid sequence of the alpha 2 heavy chain of a human IgA2 immunoglobulin of the A2m(2) allotype has been determined and is compared to the sequence of the alpha 1 chain of the human IgA1 subclass. The characteristic differences between the alpha 1 and alpha 2 chains are greatest in the hinge region and in the location and number of the oligosaccharides. Apart from the duplication in the hinge region of alpha 1 and the deletion in alpha 2, there are 23 amino acid exchanges in the constant (C) regions of the two chains. Accepted mutations are related to the surface accessibility of the residues and the proximity of carbohydrate. The results indicate that human IgA and IgG subclasses arose late in evolution and reflect similar mutationa pressures.

Immunoglobulin heavy chain constant region variants in rheumatoid arthritis.

Loftus, M G; Sanders, P; De Lange, G; Grennan, D M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1989 EN
Relevância na Pesquisa
17.7%
Polymorphisms within the immunoglobulin heavy chain constant region at switch (S)mu and S alpha 1 loci were studied in patients with rheumatoid arthritis (RA) and controls in parallel with Gm and A2m allotyping. S mu and S alpha 1 restriction fragment length polymorphisms were defined using a S mu probe which was hybridised to SstI digests of DNA extracted from circulating white cells. There were no differences in S mu and S alpha 1 gene or phenotype frequencies between RA and control groups nor within the RA population between DR4 positive and negative subjects. The Gm allotype G1m(x), coded for by genes at the gamma-1 locus, was found in 29/92 (32%) of DR4 positive and 5/52 (10%) of DR4 negative subjects with RA, as compared with 25/115 (22%) cf controls. The A2m allotype A2m(2), coded for by the alpha 2 locus, was found in 11/92 (12%) of DR4 positive subjects with RA, zero of 52 DR4 negative subjects, and 5/115 (4%) of controls. These results exclude a major effect of genes within the heavy chain constant region linked to mu or alpha 1 loci on susceptibility to RA, but suggest that further study of variants closely linked to the alpha 2 locus is indicated.

An Altered State of a Specific EN Regulatory Element Induced in a Maize Tiller

Fowler, Robert G.; Peterson, Peter A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1978 EN
Relevância na Pesquisa
17.91%
There are numerous states of the regulatory element, Enhancer (En). With specific receptor alleles, such as a2m(r-pa-pu) or a2m(r), specific mutability patterns are expressed. One specific derivative En allele, En-v (En-variable), was originally identified with a coarse pattern of mutability with the a2m(r-pa-pu) allele and giving progeny with varied En expression (standard to reduced within an ear progeny). Derivatives of En-v were subsequently found on numerous occasions to give only a very reduced expression (fewer mutant spots) with the a2m(r-pa-pu) allele in the ears derived from the main stalk of the corn plant. When a comparison is made of the effect of this changed En-v state between tiller ears and main stalk ears of the same plant, the tiller ears show an increased level of En-v expression (coarse pattern), while the main-stalk ears continue to show the very reduced level of En-v expression (low frequency of very late variegation). This increased level of mutability of the tiller ears is maintained when transmitted through the main-stalk ear in the subsequent generation. These results indicate that heritable alterations of controlling elements can be produced by endogenous environmental factors present during normal plant development.

Mannose-specific lectins bind alpha-2-macroglobulin and an unknown protein from human plasma.

Van Leuven, F.; Torrekens, S.; Van Damme, E.; Peumans, W.; Van den Berghe, H.
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em /02/1993 EN
Relevância na Pesquisa
18.29%
GNA, the mannose-specific lectin from Galanthus nivalis was confirmed to bind alpha-2-macroglobulin (A2M) but another protein was copurified with A2M from total human plasma. A total of 23 other lectins with diverse specificities were tested for reaction with human A2M and with three other members of the A2M family. NPA, a mannose-specific lectin isolated from Narcissus pseudonarcissus bulbs, and RSA, the Rhizoctonia solani agglutinin, were selected for further testing. For isolation of A2M, immobilized NPA was superior to GNA because its binding capacity was an order of magnitude higher. The specificity of these lectins must be very similar however, because the same unknown plasma protein was also bound by NPA. A2M and the unknown protein must share a unique mannose carbohydrate structure not present in any other human plasma protein. The copurified protein subunit size of 185 kDa is very similar to that of A2M, but the native molecular mass of 350 kDa indicated a noncovalent homodimer structure. Together with the acid isoelectric point this is not typical for any known plasma protein nor for any unidentified spot on the two-dimensional map of human plasma proteins. No immunological reaction with available antisera was evident. A specific antiserum raised to the unknown protein demonstrated its presence in all human plasma samples examined. The N-terminal residue was blocked...

Optimizing Screening for Acute Human Immunodeficiency Virus Infection with Pooled Nucleic Acid Amplification Tests▿ †

Westreich, Daniel J.; Hudgens, Michael G.; Fiscus, Susan A.; Pilcher, Christopher D.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
17.7%
Recent studies have shown the public health importance of identifying individuals with acute human immunodeficiency virus infection (AHI); however, the cost of nucleic acid amplification testing (NAAT) makes individual testing of at-risk individuals prohibitively expensive in many settings. Pooled NAAT (or group testing) can improve efficiency and test performance of testing for AHI, but optimizing the pooling algorithm can be difficult. We developed simple, flexible biostatistical models of specimen pooling with NAAT for the identification of AHI cases; these models incorporate group testing theory, operating characteristics of biological assays, and a model of viral dynamics during AHI. Pooling algorithm sensitivity, efficiency (test kits used per individual specimen evaluated), and positive predictive value (PPV) were modeled and compared for three simple pooling algorithms: two-stage minipools (D2), three-stage hierarchical pools (D3), and square arrays with master pools (A2m). We confirmed the results by stochastic simulation and produced reference tables and a Web calculator to facilitate pooling by investigators without specific biostatistical expertise. All three pooling strategies demonstrated improved efficiency and PPV for AHI case detection compared to individual NAAT. D3 and A2m algorithms generally provided better efficiency and PPV than D2; additionally...

A study of serum zinc, albumin, alpha-2-macroglobulin and transferrin levels in acute and long stay elderly hospital patients.

Craig, G. M.; Evans, S. J.; Brayshaw, B. J.; Raina, S. K.
Fonte: BMJ Group Publicador: BMJ Group
Tipo: Artigo de Revista Científica
Publicado em /03/1990 EN
Relevância na Pesquisa
17.7%
Serum zinc levels measured by atomic absorption spectrophotometry were found to be low (less than 10.5 mumols/l) in 38% of acute geriatric admissions, 69% of long stay geriatric patients and 19% of a control group of elderly hospital patients with a normal serum albumin. There was a significant positive correlation between serum zinc and serum albumin in all groups. In acutely ill geriatric patients only, there was a weak but statistically significant positive correlation between serum zinc and alpha-2-macroglobulin (A2M) (r = 0.20), P less than 0.05). Serum transferrin was low in 46% of acute geriatric patients and 22% of long stay geriatric patients but there was no correlation between serum zinc and serum transferrin levels in any patient group. There were significant differences in serum zinc, A2M and transferrin levels between the acute and long stay geriatric patients. The differences in serum zinc levels between these patients groups could not be explained by changes in serum A2M, transferrin or albumin. Changes mediated by an acute phase response may have influenced results in the acute geriatric group of patients.

Prostate cancer serum biomarker discovery through proteomic analysis of alpha-2 macroglobulin protein complexes

Burgess, Earle F.; Ham, Amy-Joan L.; Tabb, David L.; Billheimer, Dean; Roth, Bruce J.; Chang, Sam S.; Cookson, Michael S.; Hinton, Timothy J.; Cheek, Kristin L.; Hill, Salisha; Pietenpol, Jennifer A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 30/07/2008 EN
Relevância na Pesquisa
18.05%
Alpha-2 macroglobulin (A2M) functions as a universal protease inhibitor in serum and is capable of binding various cytokines and growth factors. In this study, we investigated if immunoaffinity enrichment and proteomic analysis of A2M protein complexes from human serum could improve detection of biologically relevant and novel candidate protein biomarkers in prostate cancer. Serum samples from six patients with androgen-independent, metastatic prostate cancer and six control patients without malignancy were analyzed by immunoaffinity enrichment of A2M protein complexes and MS identification of associated proteins. Known A2M substrates were reproducibly identified from patient serum in both cohorts, as well as proteins previously undetected in human serum. One example is heat shock protein 90 alpha (HSP90α), which was identified only in the serum of cancer patients in this study. Using an ELISA, the presence of HSP90α in human serum was validated on expanded test cohorts and found to exist in higher median serum concentrations in prostate cancer (n = 18) relative to control (n = 13) patients (median concentrations 50.7 versus 27.6 ng/mL, respectively, p = 0.001). Our results demonstrate the technical feasibility of this approach and support the analysis of A2M protein complexes for proteomic-based serum biomarker discovery.

An association analysis of Alzheimer disease candidate genes detects an ancestral risk haplotype clade in ACE and putative multilocus association between ACE, A2M, and LRRTM3

Edwards, Todd L.; Pericak-Vance, Margaret; Gilbert, Johnny; Haines, Jonathan L.; Martin, Eden; Ritchie, Marylyn D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 05/07/2009 EN
Relevância na Pesquisa
27.36%
Alzheimer’s disease (AD) is the most common form of progressive dementia in the elderly. It is a neurodegenerative disorder characterized by the neuropathologic findings of intracellular neurofibrillary tangles and extracellular amyloid plaques that accumulate in vulnerable brain regions. AD etiology has been studied by many groups, but since the discovery of the APOE ε4 allele, no further genes have been mapped conclusively to the late-onset form of the disease. In this study, we examined genetic association with late-onset Alzheimer’s susceptibility in 738 Caucasian families with 4704 individuals and an independent case-control dataset with 296 unrelated cases and 566 unrelated controls exploring 11 candidate genes with 47 SNPs common to both samples. In addition to tests for main effects and haplotype analyses, the Multifactor Dimensionality Reduction Pedigree Disequilibrium Test (MDR-PDT) was used to search for single-locus effects as well as 2-locus and 3-locus gene-gene interactions associated with AD in the family data. We observed significant haplotype effects in ACE in both family and case-control samples using standard and cladistic haplotype models. ACE was also part of significant 2-locus and 3-locus MDR-PDT joint effects models with Alpha-2-Macroglobulin (A2M)...

Surfactant Protein D Interacts with α2-Macroglobulin and Increases Its Innate Immune Potential*

Craig-Barnes, Hayley A.; Doumouras, Barbara S.; Palaniyar, Nades
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
18.29%
Surfactant protein D (SP-D) is an innate immune collectin that recognizes microbes via its carbohydrate recognition domains, agglutinates bacteria, and forms immune complexes. During microbial infections, proteases, such as elastases, cleave the carbohydrate recognition domains and can inactivate the innate immune functions of SP-D. Host responses to counterbalance the reduction of SP-D-mediated innate immune response under these conditions are not clearly understood. We have unexpectedly identified that SP-D could interact with protein fractions containing ovomucin and ovomacroglobulin. Here, we show that SP-D interacts with human α2-macroglobulin (A2M), a protease inhibitor present in the lungs and serum. Using enzyme-linked immunosorbent assays, surface plasmon resonance, and carbohydrate competition assays, we show that SP-D interacts with A2M both in solid phase (KD of 7.33 nm) and in solution via lectin-carbohydrate interactions under physiological calcium conditions. Bacterial agglutination assays further show that SP-D·A2M complexes increase the ability of SP-D to agglutinate bacteria. Western blot analyses show that SP-D, but not A2M, avidly binds bacteria. Interestingly, intact and activated A2M also protect SP-D against elastase-mediated degradation...

The essentiality of alpha-2-macroglobulin in human salivary innate immunity against new H1N1 swine origin influenza A virus

Chen, Chao-Hsuan; Zhang, Xing-Quan; Lo, Chih-Wei; Liu, Pei-Feng; Liu, Yu-Tsueng; Gallo, Richard L.; Hsieh, Ming-Fa; Schooley, Robert T.; Huang, Chun-Ming
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/2010 EN
Relevância na Pesquisa
17.91%
A novel strain of influenza A H1N1 emerged in the spring of 2009 and has spread rapidly throughout the world. Although vaccines have recently been developed that are expected to be protective, their availability was delayed until well into the influenza season. While anti-influenza drugs such as neuraminidase inhibitors can be effective, resistance to these drugs has already been reported. Although human saliva was known to inhibit viral infection and may thus prevent viral transmission, the components responsible for this activity on influenza virus, in particular, influenza A swine origin influenza A virus (S-OIV), have not yet been defined. By using a proteomics approach in conjunction with beads that bind alpha 2,6-sialylated glycoprotein, we determined that an alpha-2-macroglobulin (A2M) and a A2M-like protein are essential components in salivary innate immunity against hemagglutination mediated by a clinical isolate of S-OIV [San Diego/01/09 (SD/H1N1-S-OIV)]. A model of an A2M-based “double-edged sword” on competition of alpha 2,6-sialylated glycoprotein receptors and inactivation of host proteases is proposed. We emphasize that endogenous A2M in human innate immunity functions as a natural inhibitor against S-OIV.

Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects

Millard, Steven P.; Lutz, Franziska; Li, Ge; Galasko, Douglas R.; Farlow, Martin R.; Quinn, Joseph F.; Kaye, Jeffrey A.; Leverenz, James B.; Tsuang, Debby; Yu, Chang-En; Peskind, Elaine R.; Bekris, Lynn M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.7%
Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer’s disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5′ and 3′ regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls, but not in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels.

Tracheobronchial Protease Inhibitors, Body Surface Area Burns, and Mortality in Smoke Inhalation

Kurzius-Spencer, Margaret; Foster, Kevin; Littau, Sally; Richey, Karen J.; Clark, Beth M.; Sherrill, Duane; Boitano, Scott; Caruso, Daniel M.; Burgess, Jefferey L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2009 EN
Relevância na Pesquisa
18.15%
The objective of this study was to assess tracheobronchial protease inhibitor concentrations longitudinally and determine whether initial concentrations predict subsequent lung injury and mortality in intubated burn victims. Tracheobronchial suction fluid was collected every 2 hours for 36 hours. Alpha-1-antitrypsin (AAT), secretory leukocyte peptidase inhibitor (SLPI), alpha-2-macroglobulin (A2M), and cell and differential counts were assayed. Partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FIO2) and peak airway pressure (PAP) were recorded for 72 hours. Standard statistics were used to evaluate cross-sectional relationships; random coefficient (mixed) models were used to evaluate temporal trends in marker concentrations and relation to clinical outcomes. Among 29 patients, 24 (83%) developed hypoxemia (PaO2/FIO2 <200); six died within 2 weeks. When adjusted for gender, age, %TBSA burn, and positive end-expiratory pressure setting, A2M (P = .007) and neutrophils (P = .032) increased linearly during 36 hours, and SLPI decreased (P = .038). Initial SLPI concentration was a negative predictor of maximum PAP (P = .009). None of the markers predicted longitudinal change in PaO2/FIO2. Mean levels of AAT and A2M in initial samples were significantly lower in patients with >35% TBSA burn (P = .010 and .033...

Depletion of potential A2M risk haplotype for Alzheimer's disease in long-lived individuals

Flachsbart, Friederike; Caliebe, Amke; Nothnagel, Michael; Kleindorp, Rabea; Nikolaus, Susanna; Schreiber, Stefan; Nebel, Almut
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.7%
Risk alleles for age-related diseases are expected to decrease in frequency in the population strata of increasing age. Consistent with this hypothesis, earlier studies showed a depletion of the Alzheimer's disease risk factor APOE*ɛ4 in long-lived individuals (LLIs). To evaluate whether this observation also holds for a previously suggested Alzheimer's disease risk haplotype in the A2M gene, we analyzed this particular haplotype in 1042 German LLIs (aged 95–100 years) and 1040 younger individuals (aged 60–75 years). Our results show a significant depletion of this haplotype in LLIs, thus confirming it as a mortality factor in the elderly. Consequently, our data support an involvement of the suggested A2M risk haplotype in the pathogenesis of Alzheimer's disease and adds new evidence to the risk-allele depletion hypothesis.

The a2m(r-Pa-Pu) Allele of the En-Controlling Element System in Maize

Fowler, Robert; Peterson, Peter A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1974 EN
Relevância na Pesquisa
28.15%
The Enhancer (En) controlling element system in maize includes numerous alleles, one of which, a2m(r-pa-pu), was recovered as a derivative of the a2m(1 1511) allele. The behavior and composition of this allele is described. In the presence of the independently inherited regulatory element, En, the a2m(r-pa-pu) allele mutates and expresses in the aleurone purple, pale and colorless sectors within a colorless background. In the absence of En, the pigmentation is uniformly pale. Colored and colorless germinal mutations of the a2m(r-pa-pu) allele were recovered, although the derivative alleles tested did not respond to En. Uniformly colored derivatives, designated A2', arise only from states of a2m(r-pa-pu) that respond to an active En at relatively early stages in plant development, suggesting that somatic and germinal mutations may arise through similar events. Mutations to A2-expressing alleles appear to occur relatively late in plant development, that is, at or near meiosis, since recognizable mutant sectors do not appear on testcross ears. Kernels exhibiting such mutants are randomly distributed over the ear. The resulting A2' alleles express pigmentation ranging in a continual sequential series from dark pale to intense purple.