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1.
Public Health ; 232: 170-177, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788493

RESUMO

OBJECTIVES: Disaster evacuation increases the risk of becoming overweight or obese owing to lifestyle changes and psychosocial factors. This study evaluated the effect of evacuation on becoming overweight during a 7-year follow-up among residents of Fukushima Prefecture during the Great East Japan Earthquake. STUDY DESIGN: This was a prospective cohort study. METHODS: We analysed data collected from 18,977 non-overweight Japanese participants who completed the 'Comprehensive Health Checkup Program' and 'Mental Health and Lifestyle Survey', as part of the Fukushima Health Management Survey, between July 2011 and November 2012. An evacuation was defined as the moving out of residents of municipalities designated as an evacuation zone by the government or having a self-reported experience of moving into shelters or temporary housing. Follow-up examinations were conducted in March 2018 to identify patients who became overweight. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using a Cox proportional hazards regression model. RESULTS: Among 15,875 participants (6091 men and 9784 women; mean age 63.0 ± 11.1 years) who received follow-up examination (mean follow-up, 4.29 years), 2042 (856 men and 1186 women) became overweight. Age-, baseline body mass index-, lifestyle-, and psychosocial status-adjusted HRs (95% CIs) for becoming overweight after evacuation were 1.44 (1.24-1.66) for men and 1.66 (1.47-1.89) for women. CONCLUSION: Evacuation was associated with the risk of becoming overweight 7 years after the disaster. Thus, maintaining physical activity, healthy diet, and sleep quality and removing barriers to healthy behaviour caused by disasters, including anxiety concerning radiation, may prevent this health risk among evacuees.


Assuntos
Terremotos , Sobrepeso , Humanos , Masculino , Feminino , Japão/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Sobrepeso/epidemiologia , Idoso , Seguimentos , Acidente Nuclear de Fukushima , Inquéritos Epidemiológicos , Fatores de Risco , Desastres , Índice de Massa Corporal , Estilo de Vida
2.
Clin Exp Immunol ; 158(3): 281-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19793334

RESUMO

Interleukin (IL)-1beta is a proinflammatory cytokine and has been implicated in the pathogenesis of several autoimmune diseases. To evaluate the hypothesis that the functional -31C/T polymorphism (rs1143627) in the gene encoding IL-1beta is associated with the intractability and the severity of autoimmune thyroid diseases, we genotyped this polymorphism in 64 patients with intractable Graves' disease (GD), 28 GD patients in remission, 49 patients with Hashimoto's disease (HD) who developed hypothyroidism (severe HD), 28 untreated euthyroid HD patients (mild HD) and 59 healthy volunteers. The -31T allele, which is related to the high producibility of IL-1beta, was significantly more frequent in patients with intractable GD than in those with GD in remission (P = 0.0017; odds ratio 2.8; 95% confidence interval 1.5-5.3), although there was no difference in this frequency between two groups of HD patients. We showed additionally that the proportion of IL-17-producing T helper type 17 (Th17) cells, whose differentiation and proliferation are promoted by IL-1beta, was higher in autoimmune thyroid disease patients with the T allele than in those with CC genotypes. In conclusion, our data indicated that the T allele of -31C/T polymorphism in the IL1B gene was involved in the intractability of GD, and this involvement may arise through the differentiation and proliferation of Th17 cells.


Assuntos
Doença de Graves/genética , Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Idoso , Feminino , Frequência do Gene , Genótipo , Doença de Graves/imunologia , Doença de Hashimoto/genética , Doença de Hashimoto/imunologia , Humanos , Interleucina-17/biossíntese , Masculino , Pessoa de Meia-Idade
4.
Neuron ; 12(5): 997-1010, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8185954

RESUMO

Activation of PI-PLC initiates two independent branches of protein phosphorylation cascades catalyzed by either PKC or Ca2+/calmodulin-dependent protein kinase (CaMK). We find that phosrestin I (PRI), a Drosophila homolog of vertebrate photoreceptor arrestin, undergoes light-induced phosphorylation on a subsecond time scale which is faster than that of any other protein in vivo. We determine that a CaMK activity is responsible for in vitro PRI phosphorylation at Ser366 in the C-terminal tryptic segment, MetLysSer(P)IleGluGlnHisArg, in which Ser(P) represents phosphoserine366. We also demonstrate that Ser366 is the phosphorylation site of PRI in vivo by identifying the molecular species resulting from in-gel tryptic digestion of purified phospho-PRI using HPLC-electrospray ionization tandem quadrupole mass spectroscopy. From these data, we conclude that the CaMK pathway, not the PKC pathway, is responsible for the earliest protein phosphorylation event following activation of PI-PLC in living Drosophila photoreceptors.


Assuntos
Arrestinas , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Hormônios de Inseto/metabolismo , Fosfoproteínas/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Células Fotorreceptoras de Invertebrados/metabolismo , Sequência de Aminoácidos , Animais , Antígenos/química , Escuridão , Drosophila , Proteínas do Olho/química , Hormônios de Inseto/química , Hormônios de Inseto/efeitos da radiação , Cinética , Luz , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/isolamento & purificação , Fragmentos de Peptídeos/metabolismo , Fosfatidilinositol Diacilglicerol-Liase , Fosfoinositídeo Fosfolipase C , Fosfoproteínas/química , Fosfoproteínas/efeitos da radiação , Fosforilação , Fosfosserina/análise , Células Fotorreceptoras de Invertebrados/efeitos da radiação , Desnaturação Proteica , Dobramento de Proteína , Homologia de Sequência de Aminoácidos , beta-Arrestinas
6.
J Nutr Health Aging ; 22(3): 341-353, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29484347

RESUMO

OBJECTIVES: This study aimed to examine the relationships among subjective well-being, food and health behaviors, socioeconomic factors, and geography in chronically ill older Japanese adults living alone. DESIGN: The design was a cross-sectional, multilevel survey. A questionnaire was distributed by post and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select a representative sample of older people living alone based on their proximity to a supermarket. Study recruitment was conducted with municipal assistance. MEASUREMENTS: To assess subjective well-being and food and health behaviors of respondents with disease, a logistic regression analysis was performed using stepwise variable analyses, adjusted for respondent age, socioeconomic status, and proximity to a supermarket. The dependent variable was good or poor subjective well-being. RESULTS: In total, 2,165 older people (744 men, 1,421 women) completed the questionnaire (63.5% response rate). Data from 737 men and 1,414 women were used in this study. Among people with a chronic disease, individuals with good subjective well-being had significantly higher rates than those with poor subjective well-being for satisfaction with meal quality and chewing ability, food diversity, food intake frequency, perception of shopping ease, having someone to help with food shopping, eating home-produced vegetables, preparing breakfast themselves, eating with other people, and high alcohol consumption. A stepwise logistic analysis showed that the factors strongly related to poor subjective well-being were shopping difficulty (men: odds ratio [OR] = 3.19, 95% confidence interval [CI], 1.94-5.23; P < 0.0001; women: OR = 2.20, 95% CI, 1.54-3.14; P < 0.0001), not having someone to help with food shopping (women: OR = 1.41, 95% CI, 1.01-1.97; P = 0.043), not preparing breakfast (women: OR = 2.36, 95% CI, 1.40-3.98; P = 0.001), and eating together less often (women: OR = 1.99, 95% CI, 1.32-3.00; P = 0.002). CONCLUSION: Subjective well-being of people with chronic diseases is associated with food intake and food behavior. The factors that affect poor subjective well-being in chronically ill older Japanese people living alone include food accessibility and social communication.


Assuntos
Doença Crônica/psicologia , Comportamento Alimentar/psicologia , Comportamentos Relacionados com a Saúde , Qualidade de Vida/psicologia , Características de Residência/estatística & dados numéricos , Classe Social , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Demografia/estatística & dados numéricos , Dieta , Ingestão de Alimentos , Hipersensibilidade a Ovo , Feminino , Abastecimento de Alimentos , Fragilidade , Humanos , Renda , Japão/epidemiologia , Masculino , Refeições , Razão de Chances , Satisfação Pessoal , Estudos Prospectivos , Fatores Socioeconômicos , Inquéritos e Questionários , Verduras
7.
J Nutr Health Aging ; 21(6): 662-672, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28537330

RESUMO

OBJECTIVE: This study aimed to examine the relationships between eating together and subjective health, frailty, food behaviors, food accessibility, food production, meal preparation, alcohol intake, socioeconomic factors and geography among older Japanese people who live alone. DESIGN: A cross-sectional, multilevel survey was designed. The questionnaire was distributed by post and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select a representative sample of older people who lived alone based on their proximity to a supermarket. Recruitment for the study was conducted with municipal assistance. MEASUREMENTS: A logistic regression analysis was performed that adjusted for the respondent's age, socioeconomic status and proximity to a supermarket using stepwise variable analyses. The dependent variable was whether the respondent ate together more or less than once a month. RESULTS: In total, 2,196 older people (752 men and 1,444 women) completed the questionnaire (63.5% response rate). It was found that 47.1% of men and 23.9% of women ate together less than once a month. Those who ate together less than once a month had a significantly lower rate of subjective health, food diversity and food intake frequency than those who ate together more often. A stepwise logistic analysis showed that the factors most strongly related to eating together less than once a month were not having any food shopping assistance (men: OR = 3.06, women: OR = 2.71), not receiving any food from neighbors or relatives (men: OR = 1.74, women: OR = 1.82), daily alcohol intake (women: OR = 1.83), frailty (men: OR = 0.48) and income (men: OR = 2.16, women: OR = 1.32). CONCLUSION: Eating together is associated with subjective health and food intake. Factors that affect how often older Japanese people who live alone eat together include food accessibility, daily alcohol intake, frailty and a low income.


Assuntos
Consumo de Bebidas Alcoólicas , Ingestão de Energia , Comportamento Alimentar , Abastecimento de Alimentos , Idoso Fragilizado , Meio Social , Isolamento Social , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Demografia , Ingestão de Alimentos , Feminino , Nível de Saúde , Humanos , Renda , Japão , Modelos Logísticos , Masculino , Características de Residência , Classe Social , Inquéritos e Questionários
8.
Biochim Biophys Acta ; 588(2): 181-92, 1979 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-228755

RESUMO

A study has been made of the association and the temperature-dependent conformation of adenosine 3',5'-monophosphate (cyclic AMP) in a neutral aqueous (2H2O) solution by means of proton magnetic resonance chemical shift and relaxation. The concentration and temperature-dependent chemical shifts of H(1'), H(2), and H(8), have enabled us to estimate the self-association constant, Ka = 1.1 +/- 0.3 M-1 at 25 degrees C and thermodynamic parameters delta H = -5.8 +/- 1.5 kcal/mol and delta S (25 degrees C) = -19.0 +/- 3 cal/mol per degree. The NMR-DESERT (Deuterium Substitution Effect on Relaxation Times) method has been utilized for the determination of the syn-anti conformational equilibrium in the monomeric state and for the determination of the mutual orientation of the two adenine rings in the dimeric state of cyclic AMP. The molecules were found to coexist with nearly equimolarity or syn-anti conformers and thermal activation of the molecules perturbs the syn-anti conformational equilibrium to comprise the syn form in preference at higher temperature. The glycosidic isomerization (from anti to syn) was found to be characterized both by a positive enthalpy change and by a positive entropy change. The cyclic AMP molecules prefer to take a 'trans-stacking' conformation in the dimeric state where the two molecules are arranged in such a way that the H(2) of one molecule is close to the H(8) of the other.


Assuntos
AMP Cíclico , Fenômenos Químicos , Físico-Química , Glicosídeos , Isomerismo , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Temperatura , Termodinâmica
9.
Biochim Biophys Acta ; 755(1): 50-5, 1983 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-6186290

RESUMO

The effect of isobutylmethylxanthine on the photoresponse and the phosphorylation of phosphatidylinositol was studied. The recovery of photoresponse after a bright flash was greatly altered by the addition of isobutylmethylxanthine. Phosphatidylinositol phosphorylation, assessed by the incorporation of label from [gamma-32P]ATP, was influenced by isobutylmethylxanthine. Incorporation of 32P was decreased into diphosphoinositide and triphosphoinositide, and increased into phosphatidic acid. These changes were interpreted by introducing a parameter, phi, calcium charge of the plasma membrane.


Assuntos
1-Metil-3-Isobutilxantina/farmacologia , Fosfatidilinositóis/metabolismo , Células Fotorreceptoras/fisiologia , Retina/fisiologia , Teofilina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , GMP Cíclico/farmacologia , Escuridão , Cinética , Luz , Octopodiformes , Fosforilação , Estimulação Luminosa , Células Fotorreceptoras/efeitos dos fármacos , Retina/efeitos dos fármacos
10.
Biochim Biophys Acta ; 510(2): 305-15, 1978 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-208609

RESUMO

A calcium sensitive univalent cation channel could be formed by lysotriphosphoinositide on an artificial bilayer membrane made of oxidized cholesterol. The modified membrane was selectively permeable to univalent cations, but was only very sparingly permeable to anions or divalent cations. Selectivity sequence among group IA cations was Rb+ greater than Cs+ greater than Na+ greater than K+ greater than Li+. The conductance of the membrane was increased up to a value of about 10-2 ohm-1/cm2 with an increase in the concentration of univalent cation, and was drastically depressed by a relatively small increase in the concentration of calcium ion or other divalent cations. The sequence of depressing efficiency among divalent cations was Zn+ greater than Cd2+ greater than Ca2+ greater than Sr2+ greater than Mg2+.


Assuntos
Cálcio , Lipossomos , Fosfatidilinositóis , Cátions Monovalentes , Colesterol , Condutividade Elétrica , Lisofosfolipídeos , Potenciais da Membrana , Permeabilidade , Fosfatos de Fosfatidilinositol
11.
R Soc Open Sci ; 2(6): 150072, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26543584

RESUMO

The burrowing polymitarcyid mayfly Ephoron shigae is distributed across Japan, Korea, northeast China and far east Russia. Some populations are bisexual, and others are unisexual, i.e. geographically parthenogenetic throughout Japan. In general, parthenogenetic organisms are often found in harsh environments, such as at high latitudes and altitudes, in xeric as opposed to mesic conditions, in isolated habitats such as islands and island-like areas, and at the peripheral regions of the taxon's range. In E. shigae, however, the distributions of bisexual and unisexual populations overlap broadly in their respective geographical ranges. In the analysis of mitochondrial 16S rRNA and COI, we revealed that unisexual populations were of monophyletic origin and recently differentiated somewhere in western Japan. In the nuclear DNA EFI-α analysis, parthenogenetic strains had two genotypes, i.e. the heterozygous genotype of E1/E3 and the homozygous genotype of E1/E1 or E3/E3, while specimens of bisexual lineage had 20 genotypes. These results are consistent with an automixis mode of reproduction for the parthenogenetic strains, and also support the monophyletic origin of the parthenogenetic strains. Furthermore, there would be no gene flow between the specimens of the bisexual lineage and those of the parthenogenetic strain.

12.
Protein Sci ; 4(4): 729-39, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7613470

RESUMO

The POU-homeodomain (POUH) forms the bipartite DNA-binding POU domain in association with the POU-specific domain. The 1H, 15N, and 13C magnetic resonances of the 67-amino acid long POUH of mouse Oct-3 have almost completely been assigned, mainly through the combined use of three-dimensional triple resonance NMR methods. Based on the distance and dihedral angle constraints derived from the NMR data, the solution structure of the POUH domain has been calculated by the ab initio simulated annealing method. The average RMS deviation for all backbone heavy atoms of the 20 best calculated structures for residues 9-53 of the total 67 amino acid residues is 0.44 A. The POUH domain consists of three alpha-helices (helix-I, 10-20; helix-II, 28-38; and helix-III, 42-53), and helices-II and -III form a helix-turn-helix motif. In comparison with other classical homeodomains, the folding of the three helices is quite similar. However, the length of helix-III is fairly short. In the complex of the Oct-1 POU domain with an octamer site (Klemm JD, et al., 1994, Cell 77:21-32), the corresponding region is involved in helix-III. The structural difference between these two cases will be discussed.


Assuntos
Proteínas de Ligação a DNA/química , Proteínas de Homeodomínio/química , Fatores de Transcrição/química , Sequência de Aminoácidos , Animais , Espectroscopia de Ressonância Magnética , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Fator 3 de Transcrição de Octâmero , Fatores do Domínio POU , Conformação Proteica , Estrutura Secundária de Proteína
13.
FEBS Lett ; 338(2): 203-6, 1994 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-8307181

RESUMO

In vivo phosphorylation of P gamma, an inhibitory subunit of cGMP-phosphodiesterase of frog (Rana catesbeiana) photoreceptor rod outer segments, was investigated using a quick-freezing technique and a newly developed method for the preparation of rod outer segments. Light-dependent phosphorylation of P gamma was observed. Okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A, enhanced the apparent incorporation of 32P into P gamma, suggesting that P gamma is in equilibrium between phosphorylation and dephosphorylation. Neither phorbol ester, a potent activator of protein kinase C, nor changes in the extracellular Ca2+ concentration affected the in vivo phosphorylation of P gamma.


Assuntos
3',5'-GMP Cíclico Fosfodiesterases/metabolismo , Luz , Células Fotorreceptoras/enzimologia , Segmento Externo da Célula Bastonete/enzimologia , Animais , Eletroforese em Gel Bidimensional , Fosfatos/metabolismo , Radioisótopos de Fósforo , Fosforilação , Rana catesbeiana
14.
FEBS Lett ; 321(2-3): 107-10, 1993 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-8097478

RESUMO

Most of the 1H and 15N magnetic resonances of the 66 amino acid long POU homeodomain of mouse Oct-3 have been assigned by the combined use of the two-dimensional homonuclear, and two- and three-dimensional heteronuclear NMR methods. The sequential NOE connectivities and amide proton exchange measurements indicate the presence of three helical regions within the domain. The positions of the three helices correspond well to those of other homeodomains, the three-dimensional structures of which have already been determined. The present NMR study provides the first experimental evidence for the existence of a helix-turn-helix motif in the oct-3 POU homeodomain.


Assuntos
Proteínas de Ligação a DNA/química , Genes Homeobox , Estrutura Secundária de Proteína , Fatores de Transcrição/química , Sequência de Aminoácidos , Animais , Sítios de Ligação , Clonagem Molecular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Escherichia coli/genética , Hidrogênio , Espectroscopia de Ressonância Magnética/métodos , Camundongos , Dados de Sequência Molecular , Isótopos de Nitrogênio , Fator 3 de Transcrição de Octâmero , Proteínas Recombinantes/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
15.
FEBS Lett ; 410(2-3): 136-40, 1997 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-9237616

RESUMO

The adaptor protein Shc was prepared as glutathione S-transferase fusion proteins (GST-Shc) and used as in vitro substrate for c-Src. Since phosphotyrosine-binding domain of Shc has been shown to bind phosphatidyl-inositol 4,5-bisphosphate (PtdIns(4,5)P2) [Zhou et al. (1995) Nature 378, 584-592], effect of PtdIns(4,5)P2 on the phosphorylation of GST-Shc by c-Src was examined. PtdIns(4,5)P2 stimulated the phosphorylation of GST-Shc without any effect on the c-Src activity as judged by both its autophosphorylation and phosphorylation of exogenous substrate, Cdc2 peptide. On the other hand, phosphatidylserine, phosphatidic acid, phosphatidylinositol, and phosphatidylinositol 4-phosphate but not phosphatidylcholine stimulated the c-Src activity itself. Km for GST-Shc in the presence of 1 microM PtdIns(4,5)P2 was calculated to be 90 nM. The PtdIns(4,5)P2-dependent phosphorylation of GST-Shc was inhibited by a GST-fusion protein containing the phosphotyrosine-binding domain of Shc. These results suggest that PtdIns(4,5)P2 can act as a regulator of phosphorylation of Shc by c-Src through its binding to Shc.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Adaptadoras de Transporte Vesicular , Fosfatidilinositol 4,5-Difosfato/metabolismo , Proteínas/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Células 3T3 , Animais , Bovinos , Camundongos , Fosforilação , Proteínas/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Adaptadoras da Sinalização Shc , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src , Domínios de Homologia de src/genética
16.
J Comp Neurol ; 366(2): 231-43, 1996 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-8698884

RESUMO

The detailed morphology of rat phrenic motoneurons (PMs) was studied in 40 electrophysiologically identified cells with intracellular injection of Neurobiotin. In 15 cells, the dendritic trees were fully analyzed by using path-distance analysis, and total surface area and volume were estimated. Based on their relative onset times (ROT; i.e., the time of firing onset relative to the onset of whole phrenic activity), PMs were classified into three types; early recruited (type E; ROT < 10%), late recruited (type L; ROT > 12.5%), and quiescent (type Q; not recruited under normal conditions). Dendrites constituted 93.3% of the surface area of cells and 38.9% of the cell volumes. The number of primary dendrites (nPD) averaged 10.1, and the mean number of terminations was 38.8. The combined diameters of primary dendrites of PMs correlated well with the total dendritic surface area and the number of dendritic terminations. Comparisons among cell types revealed that type Q cells had greater dendritic surface areas and volumes than type E or type L cells. With path-distance analysis, this difference was found to be due to differences between the cell types in the numbers of their dendrites, their combined dendritic lengths, and the number of their branches. The differences between these data and those available for cat motoneurons are discussed. The input resistance of PMs correlated with their total surface area but did not correlate with their somal surface area, indicating that, in rat, PM input resistance is a function of the entire neuronal membrane rather than of the somal surface alone.


Assuntos
Dendritos/fisiologia , Neurônios Motores/fisiologia , Nervo Frênico/fisiologia , Recrutamento Neurofisiológico/fisiologia , Potenciais de Ação/fisiologia , Animais , Biotina , Gatos , Tamanho Celular , Dendritos/ultraestrutura , Diafragma/inervação , Estimulação Elétrica , Eletrofisiologia , Histocitoquímica , Masculino , Neurônios Motores/ultraestrutura , Nervo Frênico/ultraestrutura , Ratos , Ratos Wistar
17.
Immunol Lett ; 76(2): 133-8, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11274732

RESUMO

Lck, a Src family protein tyrosine kinase (PTKs), is post-translationally modified by palmitoylation, a process thought to regulate the biological function, membrane affinity and glycolipid-enriched microdomain (GEM) localization of this molecule. To examine the importance of palmitoylation sites Cys3 and Cys5 in Lck, one or both of these residues was mutated to serine to create mutants S3, S5, and S3,5, respectively. Immunofluorescence and confocal microscopy of COS-7 cells transfected with these constructs showed that while S5 and S3 localized to the plasma membrane, S3,5 was localized to the cytoplasm, suggesting that palmitoylation at at least one site is essential for membrane localization. Sucrose gradient based fractionation of these mutants expressed in COS-7 cells showed that while S5 localized to GEMs in similar fashion to the wild type, GEM localization of S3 was severely inhibited. Expression of these mutants in Lck-negative JCaM1 cells showed that although S5 reconstituted activation of nuclear factor NFAT as per the wild type, S3 expression failed to do so. These results suggest that Cys3 of Lck plays a more important role than Cys5 in GEM localization and T cell activation. Additionally, it was found that the degree of T cell function recovery is positively correlated with the degree of Lck expression in GEMs.


Assuntos
Cisteína/fisiologia , Glicolipídeos/metabolismo , Ativação Linfocitária/imunologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/fisiologia , Microdomínios da Membrana/metabolismo , Linfócitos T/imunologia , Animais , Células COS , Chlorocebus aethiops , Cisteína/genética , Cisteína/metabolismo , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Mutagênese Sítio-Dirigida , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/imunologia , Frações Subcelulares
18.
Cancer Lett ; 92(1): 87-90, 1995 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-7757964

RESUMO

Effects of [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14643) or di(2-ethylhexyl) phthalate (DEHP) as peroxisome proliferators on the susceptibility of liver DNA to damage by N-nitrosodimethylamine (DMN) or methyl methane sulfonate (MMS) were investigated. Male F344 rats were administered Wy-14643 or DEHP, orally, for 1 or 10 weeks. At 1 week, the susceptibility to hepatic DNA damage by DMN or MMS was significantly increased in the Wy-14643- or DEHP-treated rats. The enhancement of the susceptibility persisted for up to 10 weeks in both peroxisome proliferator-treated groups. These findings suggest that the high susceptibility to DNA damage caused by peroxisome proliferators would amplify the DNA damage action such as spontaneous damage, leading to an increase in the risk of initiation in the hepatocarcinogenesis.


Assuntos
Carcinógenos/farmacologia , Dano ao DNA , Dietilexilftalato/farmacologia , Fígado/efeitos dos fármacos , Microcorpos/efeitos dos fármacos , Pirimidinas/farmacologia , Animais , Dimetilnitrosamina/efeitos adversos , Fígado/ultraestrutura , Masculino , Metanossulfonato de Metila/efeitos adversos , Ratos , Ratos Endogâmicos F344
19.
Cancer Lett ; 127(1-2): 1-7, 1998 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-9619851

RESUMO

Two peroxisome proliferators, [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14,643) or di(2-ethylhexyl) phthalate (DEHP), were given orally to male F-344 rats for up to 78 or 97 weeks. At 1 week, the activity of poly(ADP-ribose) polymerase (pADPRP) was increased 2- and 1.8-fold in the liver of rats treated with Wy-14,643 and DEHP, respectively. The induction of the activity was maintained at 2.5- or 2-fold for up to 52 weeks. The immunoblot and Northern blot analyses revealed that the induction of pADPRP activity would be responsible for the increase in the amount of mRNA. In addition, in the liver tumor induced by Wy-14,643 and DEHP, the pADPRP mRNA level increased 3.6- or 3.7-fold. The magnitude of the increase in the mRNA level was higher than that in the non-tumor portion. These findings suggest that the induction of pADPRP may play an important role in the hepatocarcinogenesis induced by peroxisome proliferators.


Assuntos
Carcinógenos/farmacologia , Dietilexilftalato/farmacologia , Neoplasias Hepáticas/induzido quimicamente , Fígado/enzimologia , Poli(ADP-Ribose) Polimerases/biossíntese , Pirimidinas/farmacologia , Administração Oral , Animais , Indução Enzimática , Fígado/efeitos dos fármacos , Neoplasias Hepáticas/enzimologia , Masculino , Poli(ADP-Ribose) Polimerases/genética , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos F344
20.
Arch Ophthalmol ; 116(12): 1579-82, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9869784

RESUMO

OBJECTIVE: To quantitatively compare the extent of posterior capsule opacification (PCO) after polymethylmethacrylate (PMMA), silicone, and soft acrylic intraocular lens implantation. PATIENTS AND METHODS: A total of 240 eyes from 240 patients undergoing implant surgery were randomized into 3 groups based on the type of lens implanted: PMMA, silicone, and soft acrylic. The density value of PCO in 185 eyes was quantitated approximately 2 years after surgery by a new measurement method using the Scheimpflug videophotography system. RESULTS: Twenty-one eyes (30.4%) in the PMMA group, 4 (5.7%) in the silicone group, and 2 (2.7%) in the acrylic group had already undergone Nd:YAG laser posterior capsulotomy. The mean +/- SD PCO values were 26.3 +/- 12.2 computer-compatible tape steps (CCT) in the PMMA group, 12.0 +/- 8.3 CCT in the silicone group, and 16.0 +/- 10.3 CCT in the acrylic group. The PCO value in the PMMA group was significantly greater than that in the silicone or acrylic group (P < .001). The visual acuity loss in the PMMA group was also greater than that in the silicone or acrylic group (P < .001). CONCLUSION: Based on the PCO value and capsulotomy rate, the PCO was more extensive with the PMMA lens than with either the silicone or soft acrylic lens, which led to visual acuity loss.


Assuntos
Resinas Acrílicas/efeitos adversos , Catarata/etiologia , Cápsula do Cristalino/patologia , Implante de Lente Intraocular/efeitos adversos , Polimetil Metacrilato/efeitos adversos , Elastômeros de Silicone/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Capsulorrexe , Catarata/patologia , Feminino , Humanos , Lentes Intraoculares , Masculino , Pessoa de Meia-Idade , Facoemulsificação , Acuidade Visual
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