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1.
Phys Rev Lett ; 124(10): 101102, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32216401

RESUMO

In recent years, many γ-ray sources have been identified, yet the unresolved component hosts valuable information on the faintest emission. In order to extract it, a cross-correlation with gravitational tracers of matter in the Universe has been shown to be a promising tool. We report here the first identification of a cross-correlation signal between γ rays and the distribution of mass in the Universe probed by weak gravitational lensing. We use data from the Dark Energy Survey Y1 weak lensing data and the Fermi Large Area Telescope 9-yr γ-ray data, obtaining a signal-to-noise ratio of 5.3. The signal is mostly localized at small angular scales and high γ-ray energies, with a hint of correlation at extended separation. Blazar emission is likely the origin of the small-scale effect. We investigate implications of the large-scale component in terms of astrophysical sources and particle dark matter emission.

2.
Nat Mater ; 14(7): 675-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25985459

RESUMO

In some materials the competition between superconductivity and magnetism brings about a variety of unique phenomena such as the coexistence of superconductivity and magnetism in heavy-fermion superconductors or spin-triplet supercurrent in ferromagnetic Josephson junctions. Recent observations of spin-charge separation in a lateral spin valve with a superconductor evidence that these remarkable properties are applicable to spintronics, although there are still few works exploring this possibility. Here, we report the experimental observation of the quasiparticle-mediated spin Hall effect in a superconductor, NbN. This compound exhibits the inverse spin Hall (ISH) effect even below the superconducting transition temperature. Surprisingly, the ISH signal increases by more than 2,000 times compared with that in the normal state with a decrease of the injected spin current. The effect disappears when the distance between the voltage probes becomes larger than the charge imbalance length, corroborating that the huge ISH signals measured are mediated by quasiparticles.

3.
Phys Rev Lett ; 115(19): 196602, 2015 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-26588404

RESUMO

We have measured spin Hall effects in spin glass metals, CuMnBi alloys, with the spin absorption method in the lateral spin valve structure. Far above the spin glass temperature T(g) where the magnetic moments of Mn impurities are randomly frozen, the spin Hall angle of a CuMnBi ternary alloy is as large as that of a CuBi binary alloy. Surprisingly, however, it starts to decrease at about 4T(g) and becomes as little as 7 times smaller at 0.5T(g). A similar tendency was also observed in anomalous Hall effects in the ternary alloys. We propose an explanation in terms of a simple model considering the relative dynamics between the localized moment and the conduction electron spin.

4.
Nat Genet ; 13(2): 161-6, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8640221

RESUMO

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.


Assuntos
Cromossomos Humanos Par 2 , Diabetes Mellitus Tipo 2/genética , Americanos Mexicanos/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Ligação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Japão , População Branca
5.
J Environ Radioact ; 232: 106568, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33740532

RESUMO

In the present study, 137Cs and 238U activity concentrations, 234U/238U activity ratio, and 235U/238U isotope ratio were measured in fifteen soil samples collected from the exclusion zone around the Fukushima Daiichi Nuclear Power Station (FDNPS). The 137Cs activity concentrations of Fukushima-accident contaminated soil samples ranged from 29.9 to 4780 kBq kg-1 with a mean of 2007 kBq kg-1. On the other hand, the 238U activity concentrations of these soil samples ranged from 5.2 to 22.4 Bq kg-1 with a mean of 13.2 Bq kg-1. The activity ratios of 234U/238U ranged from 0.973 to 1.023. The 235U/238U isotope ratios of these exclusion zone soil samples varied from 0.007246 to 0.007260, and they were similar to the natural terrestrial ratio confirming the natural origin. Using isotope dilution technique, the 235U/137Cs activity ratio was theoretically estimated for highly 137Cs contaminated soil samples from Fukushima exclusion zone ranged from 5.01 × 10-8 - 6.16 × 10-7 with a mean value of 2.51 × 10-7.


Assuntos
Acidente Nuclear de Fukushima , Monitoramento de Radiação , Poluentes Radioativos do Solo , Urânio , Radioisótopos de Césio/análise , Japão , Espectrometria de Massas , Plasma/química , Solo , Poluentes Radioativos do Solo/análise , Urânio/análise
6.
J Environ Radioact ; 233: 106617, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33866199

RESUMO

Various radionuclides including fission products and heavy nuclides were released into the environment during the Fukushima Daiichi Nuclear Power Station (FDNPS) accident. The dissolution followed by migration of deposited radionuclides of Cs, Sr and U on soils could take place to the local environment. Therefore, it is necessary to determine sorption-desorption coefficients of U in soil-water system around the FDNPS from a migration viewpoint. The determination of sorption coefficient Kd(S) as well as desorption coefficient Kd(D) for U has been carried out in the present study using a laboratory batch method. Stable U was used for sorption from simulated ground water onto contaminated soil samples collected from Okuma Town, Fukushima. Different soil parameters were measured to understand their effects on sorption and desorption processes. The obtained Kd(S) and Kd(D) values of U were compared with values of Kd(S) and Kd(D) of Cs and Sr and Kd(S)-U in known Fukushima accident contaminated soils reported in the literature for better understanding. It was observed that Kd(S)-U varied from 160 to 5100 L/kg, whereas Kd(D)-U ranged from 200 to 11000 L/kg. Kd(D) was higher than Kd(S) for U in these soils implying irreversibility of the sorption process. Pearson's correlation of Kd(S) values suggested that U sorption is affected by various soil parameters. However, desorption is decided by the nature of U species formed in sorption process and soil parameters like pH, presence of carbonates, Ca ions, clay minerals etc. to some extent. The comparison between Kd(S) and Kd(D) values for Cs, Sr and U revealed that unsorbed Sr could migrate farther than unsorbed Cs or U under the present experimental conditions. Both sorption and desorption studies are of great importance to understand migration of metal ions from contaminated sites to local uncontaminated areas.


Assuntos
Acidente Nuclear de Fukushima , Monitoramento de Radiação , Poluentes Radioativos do Solo , Urânio , Adsorção , Radioisótopos de Césio/análise , Solo , Poluentes Radioativos do Solo/análise , Urânio/análise
9.
Radiat Prot Dosimetry ; 184(3-4): 457-462, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095339

RESUMO

Short-term measurements were made in four different types of Chinese cave dwellings, 'ground', 'open-cut', 'aboveground' and 'underground', located in Gansu Province, China, in order to evaluate the diurnal and seasonal variations in indoor radon (222Rn) and thoron (220Rn) concentrations. As a result, in most of the 'ground' and 'open-cut' cave dwellings in summer, the indoor 222Rn concentrations during the nighttime were higher than those during the daytime. In the winter, such fluctuation was not observed. The daily indoor 222Rn concentrations in summer were higher than those in winter, excluding the 'aboveground' cave dwelling, and these concentrations depended on dwelling type, exhalation from the building materials and ventilation. In contrast with 222Rn, there seemed to be only very slight clear variations in 220Rn.


Assuntos
Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento de Radiação/métodos , Produtos de Decaimento de Radônio/análise , Radônio/análise , Poluentes Radioativos do Solo/análise , Cavernas , China , Habitação , Humanos , Estações do Ano
10.
Radiat Prot Dosimetry ; 184(3-4): 510-513, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31038711

RESUMO

In the present study, variations in ambient gamma dose rate associated with snow cover were examined in a radioactive-contaminated site in Fukushima Prefecture, Japan. The ambient gamma dose rates decreased with increasing snow depth. The reduction trends were different between fresh snow (0.1-0.2 g/cm3) and granular snow (0.3-0.4 g/cm3) depending on snow density. Snow cover water content (snow water equivalent) calculated from snow depth and density was a key parameter governing the reduction in the ambient gamma dose rate. The ambient gamma dose rates reduced to 0.6 and 0.5 at 4 g/cm2 and 8 g/cm2 of snow water equivalent, respectively. Based on gamma-ray flux density distributions, the ambient gamma dose rates from the primary gamma rays decreased more compared to those from scattered gamma rays due to snow cover.


Assuntos
Radioisótopos de Césio/análise , Acidente Nuclear de Fukushima , Monitoramento de Radiação/métodos , Neve/química , Poluentes Radioativos do Solo/análise , Raios gama , Japão , Doses de Radiação , Estações do Ano
11.
Phys Rev E Stat Nonlin Soft Matter Phys ; 75(6 Pt 2): 066401, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17677366

RESUMO

A low energy non-neutral electron plasma was confined with a magnetic mirror field and an electrostatic potential to investigate the basic confinement properties of a simple magnetic mirror trap. The mirror ratio of the magnetic field was increased up to 5. As expected the confinement time became longer as a function of the mirror ratio. The axially integrated radial density profiles in equilibrium were measured and compared with a theoretical model. The axial electrostatic oscillations of a confined electron plasma were also observed.

12.
Mol Biol Cell ; 7(6): 907-16, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8816997

RESUMO

We have characterized the function of connexin (Cx) 32 gene mutations found in X-linked dominant Charcot-Marie-Tooth disease with respect to their ability to form functional gap junctions among themselves and to inactivate wild-type Cx32 by a dominant negative mechanism. We prepared four types of Cx32 mutant cDNAs and transfected them into HeLa cells, which do not show detectable levels of gap junctional intercellular communication (GJIC), nor expression of any connexins examined. Cells transfected with the wild-type Cx32 gene, but not those transfected with three different base substitution mutations (i.e. Cys 60 to Phe, Val 139 to Met, and Arg 215 to Trp), restored GJIC. Unexpectedly, in cells transfected with a nonsense mutant at codon 220, there was also restored GJIC. When we double-transfected these mutant constructs into the HeLa cells that had already been transfected with the wild-type Cx32 gene and thus were GJIC proficient, three base substitution mutants inhibited GJIC, suggesting that these three mutants can eliminate the function of wild-type Cx32 in a dominant negative manner. The nonsense mutation at codon 220 did not show such a dominant negative effect. Since both mutant and wild-type Cx32 mRNAs were detected, but only poor Cx32 protein expression at cell-cell contact areas was observed in the double transfectants, it is suggested that certain mutants form nonfunctional chimeric connexons with wild-type connexins, which are not properly inserted into the cytoplasmic membrane.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Conexinas/genética , Mutação/genética , Cromossomo X/genética , Sequência de Aminoácidos , Comunicação Celular/genética , Comunicação Celular/fisiologia , Junções Comunicantes/fisiologia , Ligação Genética , Células HeLa , Humanos , Frações Subcelulares/química , Proteína beta-1 de Junções Comunicantes
13.
Radiat Prot Dosimetry ; 177(1-2): 36-39, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29036675

RESUMO

This article deals with the variation of radon (Rn), thoron (Tn) and their progeny concentrations expressed in terms of equilibrium equivalent concentrations (EERC and EETC), in 40 houses, in four villages of Sokobanja municipality, Southern Serbia. Two types of passive detectors were used: (1) discriminative radon-thoron detector for simultaneous Rn and Tn gases measurements and (2) direct Tn and Rn progeny sensors (DRPS/DTPS) for measuring Rn and Tn progeny concentrations. Detectors were exposed simultaneously for a single period of 12 months. Variations of Tn and EETC appear higher than those of Rn and EERC. Analysis of the spatial variation of the measured concentrations is also reported. This work is part of a wider survey of Rn, Tn and their progeny concentrations in indoor environments throughout the Balkan region started in 2011 year.


Assuntos
Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Exposição Ambiental/análise , Exposição Ocupacional/análise , Monitoramento de Radiação/métodos , Produtos de Decaimento de Radônio/análise , Radônio/análise , Sérvia
14.
Nucleic Acids Res ; 29(10): 2154-62, 2001 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-11353085

RESUMO

The expression of liver-specific genes is regulated by unequivocally allocated transcription factors via proper responsible elements within their promoters. We identified a novel transcription factor, CREB-H, and found that its expression was restricted in the liver among 16 human tissues tested. A region of CREB-H exhibited significant homology to the basic leucine zipper (b-Zip) domain of members of the CREB/ATF family: mammalian LZIP and Drosophila BBF-2 that binds to box-B, a Drosophila enhancer modulating the fat-body-specific gene expression. CREB-H contained a hydrophobic region representing a putative transmembrane domain, like LZIP. Constructing a variety of CREB-H fusion proteins with the GAL4 DNA-binding domain disclosed that CREB-H functioned as a transcriptional activator and its N-terminal 149 amino acids accounted for the activation ability. Gel mobility sift assays revealed that CREB-H did not bind to the C/EBP, AP-1 and NF-kappaB elements but specifically bound to CRE and the box-B element. Luciferase reporter assays demonstrated that like BBF-2, CREB-H activated transcription via the box-B element and that a deletion of the putative transmembrane domain increased the activation of reporter expression significantly. Furthermore, a fusion protein of GFP and full-length CREB-H was localized in reticular structures surrounding the nucleus, whereas a fusion protein of GFP and a deletion mutant lacking the putative transmembrane domain was mainly in the nucleus. These findings suggest that CREB-H plays an important role in transcriptional regulation of genes specifically expressed in the liver, and that the putative transmembrane domain may be associated with modulation of its function as the transcriptional activator.


Assuntos
Proteínas Sanguíneas/química , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/química , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Zíper de Leucina , Fígado/metabolismo , Elementos de Resposta/genética , Fatores de Transcrição/química , Fatores Ativadores da Transcrição , Sequência de Aminoácidos , Animais , Sequência de Bases , Células COS , Núcleo Celular/metabolismo , Clonagem Molecular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Citoplasma/metabolismo , Sondas de DNA/genética , Sondas de DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Éxons/genética , Humanos , Dados de Sequência Molecular , Especificidade de Órgãos , Estrutura Terciária de Proteína , Transporte Proteico , RNA Mensageiro/análise , RNA Mensageiro/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Deleção de Sequência/genética , Transativadores/química , Transativadores/genética , Transativadores/metabolismo , Ativação Transcricional
15.
Cancer Res ; 57(3): 375-7, 1997 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-9012458

RESUMO

Connexin genes have been shown to restore normal cell growth when transfected into certain tumorigenic cells and thus are considered to form a family of tumor suppressor genes. In this study, we have analyzed mutations of the connexin 37 (Cx37) gene in rat hepatic angiosarcomas induced by vinyl chloride. A total of 25 rat liver tumors (22 hepatic angiosarcomas and 3 hepatocellular carcinomas) were analyzed by PCR-single-strand conformation polymorphism analysis and DNA sequencing. Four mutations were detected in three tumors: (a) one GGG(Gly) to GAG(Glu) mutation at codon 168; and (b) three silent mutations, CGA(Arg) to CGC(Arg), at codon 166. In addition, we found that codon 88 is polymorphic (GAG(Glu) to GAA(Glu)). Cx37 proteins are detectable in endothelial cells of normal liver by immunohistochemical analysis, but none of the angiosarcomas showed Cx37-positive spots. These results suggest that Cx37-mediated gap junctional intercellular communication may be disturbed in most of these angiosarcomas, but mutation of the Cx37 gene is rare.


Assuntos
Conexinas/genética , Hemangiossarcoma/genética , Neoplasias Hepáticas Experimentais/genética , Mutação , Cloreto de Vinil/toxicidade , Animais , Conexinas/análise , Feminino , Hemangiossarcoma/induzido quimicamente , Imuno-Histoquímica , Neoplasias Hepáticas Experimentais/induzido quimicamente , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Ratos , Ratos Sprague-Dawley , Proteína alfa-4 de Junções Comunicantes
16.
Cancer Res ; 54(1): 41-4, 1994 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-8261459

RESUMO

We have examined whether alterations of simple (CA)n DNA repeats, as observed in human colon cancers, occur during human gastric carcinogenesis and whether such alterations reflect genomic instability that could lead to other genetic changes. A total of 22 gastric cancer samples were analyzed: 15 well or moderately differentiated adenocarcinomas, 6 signet-ring cell carcinomas, and 1 poorly differentiated adenocarcinoma. When (CA)n repeat sequences were examined at 10 loci, one adenocarcinoma showed a loss of repeat sequences at five loci, three adenocarcinomas gained a repeat at one locus, and one adenocarcinoma had new, repeated sequences at five loci. Three samples showed mutations in the p53 gene, two in exon 5 (both GC to AT transition at a CpG dinucleotide) and one in exon 7 (AT to GC transition). Only one sample with a p53 mutation also showed altered (CA)n repeats. A putative tumor suppressor gene, connexin 32, was not altered as assessed by single-strand conformation polymorphism analysis. These results suggest that genomic instability revealed by (CA)n repeat changes does not seem to contribute to induction of point mutations in p53 or connexin 32 genes but may participate in loss of heterozygosity at APC/MCC loci. The results are consistent with the hypothesis that different mechanisms are involved in the gain and loss of (CA)n repeats.


Assuntos
DNA de Neoplasias/genética , Deleção de Genes , Genes p53/genética , Mutação/genética , Neoplasias Gástricas/genética , Adenocarcinoma/genética , Adulto , Idoso , Sequência de Bases , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular
17.
Cancer Res ; 60(21): 6018-26, 2000 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11085522

RESUMO

Gap junction expression has been reported to control the growth of a variety of transformed cells. We undertook parallel analysis of connexins Cx32 and Cx43 in glioma cells, which revealed potential mechanisms underlying this phenomenon and led to several novel findings. Cx43, but not Cx32, suppressed C6 glioma cell growth. Paradoxically, Cx32 transfection resulted in severalfold more dye transfer than Cx43. However, Cx43 transfectants shared endogenous metabolites more efficiently than Cx32 transfectants. Interestingly, a significant portion of Cx43 permeants were incorporated into macromolecules more readily than those that transferred via Cx32. Cx43 induced contact inhibition of cell growth but in contrast to other reports, did not affect log phase growth rates. Cell death, senescence, or suppression of growth factor signaling was not involved because no significant alterations were seen in cell viability, telomerase, or mitogen-activated protein kinase activity. However, suppression of cell growth by Cx43 entailed the secretion of growth-regulatory factors. Most notably, a major component of conditioned medium that was affected by Cx43 was found to be MFG-E8 (milk fat globule epidermal growth factor 8), which is involved in cell anchorage and integrin signaling. These results indicate that Cx43 regulates cell growth by the modulation of extracellular growth factors including MFG-E8. Furthermore, the ability of a Cx to regulate cell growth may rely on its ability to mediate the intercellular transfer of endogenous metabolites but not artificial dyes.


Assuntos
Antígenos de Superfície , Conexina 43/fisiologia , Junções Comunicantes/fisiologia , Glioma/patologia , Glicoproteínas de Membrana/antagonistas & inibidores , Proteínas do Leite , Sequência de Aminoácidos , Animais , Northern Blotting , Comunicação Celular/fisiologia , Divisão Celular/fisiologia , Corantes/farmacocinética , Conexina 43/biossíntese , Conexina 43/genética , Conexinas/biossíntese , Conexinas/genética , Conexinas/fisiologia , Junções Comunicantes/metabolismo , Glioma/genética , Glioma/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , Ratos , Telomerase/metabolismo , Transfecção , Proteína beta-1 de Junções Comunicantes
18.
Radiat Prot Dosimetry ; 171(2): 172-178, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27026744

RESUMO

A comprehensive study was carried out to determine the radioactivity concentration of soil samples from different sites of a high background radiation area in the eastern coast of India, Odisha state. The dose rate measured in situ varied from 0.25 to 1.2 µSv h-1 The gamma spectrometry measurements indicated Th series elements as the main contributors to the enhanced level of radiation and allowed the authors to find the mean level of the activity concentration (±SD) for 226Ra, 228Th and 40K as 130±97, 1110±890 and 360±140 Bq kg-1, respectively. Human exposure from radionuclides occurring outdoor was estimated based on the effective dose rate, which ranged from 0.14±0.02 to 2.15±0.26 mSv and was higher than the UNSCEAR annual worldwide average value 0.07 mSv. Additionally, X-ray fluorescence analysis provided information about the content of major elements in samples and indicated the significant amount of Ti (7.4±4.9 %) in soils.


Assuntos
Potássio/análise , Rádio (Elemento)/análise , Poluentes Radioativos do Solo/análise , Tório/análise , Radiação de Fundo , Exposição Ambiental , Raios gama , Geografia , Humanos , Índia , Modelos Estatísticos , Radioisótopos de Potássio/análise , Doses de Radiação , Monitoramento de Radiação/métodos , Radioatividade , Radioisótopos/análise , Espectrometria gama/métodos , Raios X
19.
Biochim Biophys Acta ; 1351(1-2): 13-6, 1997 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-9116026

RESUMO

A novel full-length cDNA showing homology with rho genes was isolated from a human placenta cDNA library. Sequencing of a total of 1086 nucleotides of this clone revealed an open reading frame of 630 nucleotides (210 amino acids). In view of its degree of homology to members of the Rho family of molecules (50-54% identical amino acids, 60-63% identical nucleotides within the coding region), the predicted product was designated RhoHP1(Rho-related protein HP1). Northern analysis indicated that a message about 1.2-kb long is expressed in human heart, placenta, liver, skeletal muscle, and pancreas and, with weaker intensity, in several other tissues.


Assuntos
Proteínas de Ligação ao GTP/genética , Família Multigênica , Proteínas rho de Ligação ao GTP , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , Proteínas de Ligação ao GTP/classificação , Humanos , Dados de Sequência Molecular , RNA Mensageiro/análise , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Distribuição Tecidual
20.
Diabetes ; 38(9): 1090-6, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2767337

RESUMO

With isoelectric focusing, we examined heterogeneity of autoantibodies to insulin receptors in serums of two patients with insulin-resistant diabetes and one patient with hypoglycemia. Immunoglobulins were prepared by ammonium sulfate precipitation and ion-exchange chromatography with DEAE-Sepharose and subjected to isoelectric focusing for separation into 30 fractions. The fractions were tested for their ability to inhibit 125I-labeled insulin binding to human placental membranes, immunoprecipitate solubilized insulin receptor cross-linked with 125I-insulin, and mimic or inhibit the action of insulin in rat adipocytes. The results varied among the three patients. In the first patient, inhibition of 125I-insulin-binding activity (IBA) and insulin-receptor-precipitating activity (IPA) were distributed almost identically, but the distribution of insulinlike bioactivity (ILBA) was somewhat different. In the second patient, some fractions exhibited potent IBA without IPA, and these fractions inhibited the action of insulin in rat adipocytes. In the third patient, all of the isoelectric fractions showed IBA without IPA and were insulin antagonists. These observations indicate that some patients have antibodies with pure insulin-antagonist properties and provide further evidence that autoantibodies to insulin receptors are polyclonal and recognize different antigenic sites on insulin-receptor molecules. The findings also suggest that the ability of antibodies to elicit ILBA is linked to the ability to immunoprecipitate 125I-insulin-cross-linked and solubilized receptors, whereas antibodies that only inhibit insulin binding behave as insulin antagonists.


Assuntos
Anticorpos Heterófilos/análise , Autoanticorpos/análise , Anticorpos Anti-Insulina/análise , Resistência à Insulina , Receptor de Insulina/imunologia , Acantose Nigricans/imunologia , Tecido Adiposo/imunologia , Adulto , Animais , Feminino , Humanos , Hipoglicemia/imunologia , Imunoglobulina G/análise , Focalização Isoelétrica/métodos , Masculino , Pessoa de Meia-Idade , Testes de Precipitina/métodos , Ratos , Receptor de Insulina/análise
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