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1.
Clin Exp Immunol ; 202(2): 249-261, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32578199

RESUMO

While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+ CD127- regulatory T cells (edu.Tregs ) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg ; anti-A/B antibodies were not involved in the Treg -mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Antígeno B7-H1/imunologia , Células Endoteliais/imunologia , Antígenos HLA-DR/imunologia , Isoanticorpos/imunologia , Transplante de Órgãos , Linfócitos T Reguladores/imunologia , Células Endoteliais/patologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Humanos , Linfócitos T Reguladores/patologia
2.
Psychol Med ; 46(15): 3117-3125, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27534897

RESUMO

BACKGROUND: The Fukushima Daiichi and Daini Nuclear Power Plant workers experienced multiple stressors as both victims and onsite workers after the 2011 Great East Japan Earthquake and subsequent nuclear accidents. Previous studies found that disaster-related exposures, including discrimination/slurs, were associated with their mental health. Their long-term impact has yet to be investigated. METHOD: A total of 968 plant workers (Daiichi, n = 571; Daini, n = 397) completed self-written questionnaires 2-3 months (time 1) and 14-15 months (time 2) after the disaster (response rate 55.0%). Sociodemographics, disaster-related experiences, and peritraumatic distress were assessed at time 1. At time 1 and time 2, general psychological distress (GPD) and post-traumatic stress response (PTSR) were measured, respectively, using the K6 scale and Impact of Event Scale Revised. We examined multivariate covariates of time 2 GPD and PTSR, adjusting for autocorrelations in the hierarchical multiple regression analyses. RESULTS: Higher GPD at time 2 was predicted by higher GPD at time 1 (ß = 0.491, p < 0.001) and discrimination/slurs experiences at time 1 (ß = 0.065, p = 0.025, adjusted R 2 = 0.24). Higher PTSR at time 2 was predicted with higher PTSR at time 1 (ß = 0.548, p < 0.001), higher age (ß = 0.085, p = 0.005), and discrimination/slurs experiences at time 1 (ß = 0.079, p = 0.003, adjusted R 2 = 0.36). CONCLUSIONS: Higher GPD at time 2 was predicted by higher GPD and discrimination/slurs experience at time 1. Higher PTSR at time 2 was predicted by higher PTSR, higher age, and discrimination/slurs experience at time 1.


Assuntos
Acidente Nuclear de Fukushima , Saúde Mental , Centrais Nucleares , Preconceito/psicologia , Opinião Pública , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/psicologia , Adulto , Desastres , Feminino , Humanos , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Inquéritos e Questionários , Recursos Humanos
3.
Br J Cancer ; 111(12): 2308-15, 2014 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-25314067

RESUMO

BACKGROUND: Nucleostemin (NS) is essential for the maintenance of stem cell properties, the functions of which remain poorly understood in cancer cells. The purpose of this study was to explore the impact of NS on malignancy and its clinical significance in oral squamous cell carcinoma (OSCC) patients. METHODS: We investigated the effects of NS on the proliferation and invasion of OSCC using NS-overexpressing or -knockdown OSCC cells. We assessed the activation of the STAT3 (signal transducer and activator of transcription 3) signalling pathway and the downstream targets in the cells with different expression levels of NS. An immunohistochemical analysis of NS was also performed in 54 OSCC patients who were treated with preoperative chemoradiotherapy and surgery. RESULTS: The overexpression of NS significantly enhanced the proliferation and invasive potential of OSCC cells. On the other hand, downregulation of NS suppressed the invasiveness of the cells. The alterations of these malignant phenotypes were associated with the activation of STAT3 signalling and its downstream targets. An immunohistochemical analysis demonstrated that a high NS tumour expression level significantly correlated with an advanced T-stage and N-stage. Furthermore, a Cox regression analysis revealed that the NS status (hazard ratio, 9.09; P=0.002) was a significant progression factor for OSCC patients. CONCLUSIONS: Our results suggest that targeting NS may provide a promising treatment for highly malignant OSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Ligação ao GTP/biossíntese , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Bucais/metabolismo , Proteínas Nucleares/biossíntese , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células/fisiologia , Proteínas de Ligação ao GTP/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Neoplasias Bucais/genética , Proteínas Nucleares/genética , Fenótipo , Prognóstico , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Transfecção
4.
Science ; 385(6715): 1327-1331, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39298597

RESUMO

Quantum state teleportation is commonly used in designs for large-scale quantum computers. Using Quantinuum's H2 trapped-ion quantum processor, we demonstrate fault-tolerant state teleportation circuits for a quantum error correction code-specifically the Steane code. The circuits use up to 30 qubits at the physical level and employ real-time quantum error correction. We conducted experiments on several variations of logical teleportation circuits using both transversal gates and lattice surgery. We measured the logical process fidelity to be 0.975 ± 0.002 for the transversal teleportation implementation and 0.851 ± 0.009 for the lattice surgery teleportation implementation as well as 0.989 ± 0.002 for an implementation of Knill-style quantum error correction.

5.
Br J Cancer ; 107(7): 1031-6, 2012 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-22918396

RESUMO

BACKGROUND: The purpose of this study is to investigate the prognostic impact of C-reactive protein (CRP) on patients with advanced urothelial carcinoma and to develop a novel nomogram predicting survival. METHODS: A total of 223 consecutive patients were treated at Tokyo Medical and Dental Hospital. A nomogram incorporating V was developed based on the result of a Cox proportional hazards model. Its efficacy and clinical usefulness was evaluated by concordance index (c-index) and decision curve analysis. RESULTS: Of the 223 patients, 184 (83%) died of cancer. Median follow-up periods of patients who died and those who remained alive were 5 and 11 months, respectively. We developed a novel nomogram incorporating Eastern Cooperative Oncology Group Performance Status, presence of visceral metastasis, haemoglobin and age. The c-index of the nomogram predicting survival probability 6 and 12 months after diagnosis was 0.788 and 0.765, respectively. Decision curve analyses revealed that the novel nomogram incorporating CRP had a superior net benefit than that without CRP for most of the examined probabilities. CONCLUSION: We demonstrated the prognostic impact of CRP that improved the predictive accuracy of a nomogram for survival probability in patients with advanced urothelial carcinoma.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células de Transição/sangue , Técnicas de Apoio para a Decisão , Nomogramas , Neoplasias Urológicas/sangue , Idoso , Feminino , Seguimentos , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Bexiga Urinária/sangue
6.
Public Health Action ; 12(4): 148-152, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36561903

RESUMO

SETTING: Five urban TB diagnostic centres in Lusaka, Zambia. OBJECTIVE: To determine the proportion of bacteriologically confirmed pre-treatment lost to follow-up (LTFU) patients with TB found at the study settings in 2020. DESIGN: This was a retrospective cohort study in which the TB laboratory and treatment registers at the study sites were cross-matched. RESULTS: A total of 1,085 bacteriologically confirmed patients with TB were found in the laboratory TB registers at the study settings. Of these, 809 (74.6%) were males, whereas 8 (0.7%) were children, 1,005 (92.6%) were diagnosed using Xpert, 78 (7.2%) by microscopy. A total of 91 (8.4%, 95% CI 6.8-10.2) were determined to be pre-treatment LTFU. Those who had very low (14.0%, 95% CI 8.5-21.2) and low (11.8%, 95% CI 8.4-16.0) results on Xpert were respectively 3.1 (95% CI 1.6-6.0) and 2.6 (95% CI 1.4-4.8) times more likely to become pre-treatment LTFU than those who had medium (4.5%, 95% CI 2.5-7.4) results. The proportions of pre-treatment LTFU varied among the study sites from 0.7% to 16.1%. CONCLUSION: Health facilities should strive to account for every patient with TB, with particular attention to those who are bacteriologically confirmed.


CADRE: Cinq centres urbains de diagnostic de la TB à Lusaka, en Zambie. OBJECTIF: Déterminer la proportion de patients atteints de TB perdus de vue (LTFU) avant le traitement et confirmés bactériologiquement dans les centres d'étude en 2020. MÉTHODE: Il s'agit d'une étude de cohorte rétrospective dans laquelle les registres de laboratoire et de traitement de la TB des sites étudiés ont été appariés. RÉSULTATS: Au total, 1 085 patients atteints de TB confirmée par une analyse bactériologique ont été trouvés dans les registres de laboratoire de la TB des sites de l'étude. Parmi eux, 809 (74,6%) étaient des hommes, tandis que 8 (0,7%) étaient des enfants. 1 005 (92,6%) ont été diagnostiqués à l'aide d'Xpert, 78 (7,2%) par microscopie. Au total, 91 (8,4% ; IC 95% 6,8­10,2) ont été déterminés comme étant des cas de LTFU avant traitement. Ceux qui avaient obtenu des résultats très faibles (14,0% ; IC 95% 8,5­21,2) et faibles (11,8% ; IC 95% 8,4­16,0) au test Xpert étaient respectivement 3,1 (IC 95% 1,6­6,0) et 2,6 (IC 95% 1,4­4,8) fois plus susceptibles de devenir des cas de LTFU avant traitement que ceux qui avaient obtenu des résultats moyens (4,5% ; IC 95% 2,5­7,4). Les proportions de LTFU avant traitement variaient entre les sites de l'étude de 0,7% à 16,1%. CONCLUSION: Les établissements de santé devraient s'efforcer de comptabiliser tous les patients atteints de TB, en accordant une attention particulière à ceux dont la présence est confirmée par la bactériologie.

7.
Anticancer Res ; 42(4): 1777-1783, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35346996

RESUMO

BACKGROUND/AIM: As part of our continuing investigation in coumarin derivatives as potential anticancer substances, a series of alkylpsoralens were synthesized, and their antiproliferative activity was evaluated in leukemic HL60 cells. MATERIALS AND METHODS: Alkylpsoralens were systematically synthesized from the combination of several chloroketones and 7-hydroxycoumarin derivatives. RESULTS: Among the compounds synthesized, 4,4',8-trimethylpsoralen demonstrated the most potent activity (IC50=6.6 µM). CONCLUSION: The correlation between the alkylation pattern and antiproliferative activity showed the importance of the C4-methyl and C8-methyl moieties in the psoralen nucleus as well as the importance of lipophilicity for their antiproliferative activity.


Assuntos
Antineoplásicos , Antineoplásicos/química , Antineoplásicos/farmacologia , Cumarínicos/química , Células HL-60 , Humanos
8.
Public Health Action ; 11(1): 22-25, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33777717

RESUMO

SETTING: An urban TB diagnostic centre in Lusaka, Zambia. OBJECTIVE: To re-evaluate treatment outcomes of all bacteriologically confirmed TB patients registered in 2018. DESIGN: This was a retrospective cohort study on TB patients. Treatment outcomes of patients who were transferred out were retrieved. RESULTS: A total of 182 patients were registered, 26 of whom had missing documents; these were excluded from the study. Of the remaining 156 patients who were reviewed, 86 (55.1%) were correctly evaluated by the centre, 35 (22.4%) were incorrectly evaluated and 35 (22.4%) were 'transferred out' (not evaluated). As a result of this review, the number of evaluated patients increased from 86 (55.1%) to 150 (96.2%). The cure and treatment success rates rose from 43.6% and 44.2%, respectively, to 57.7% and 73.1%, respectively. Of note, 14 of the 35 patients who were initially declared 'transferred out' did not actually reach their treatment facilities and ended up being lost to follow-up. CONCLUSION: This study shows that it is possible to evaluate almost all TB patients. Re-evaluation of treatment outcomes of TB patients revealed the problems in the TB services that need to be improved in the future.


CONTEXTE: Un centre urbain de diagnostic de la TB à Lusaka, Zambie. OBJECTIF: Réévaluer les résultats du traitement de tous les patients atteints de TB bactériologiquement confirmée qui étaient enregistrés en 2018. SCHÉMA: Ceci est une étude rétrospective de cohorte de patients. Des résultats du traitement des patients TB qui ont été transferés dans un autre hôpital étaient retrouvés. RÉSULTATS: D'un total de 182 patients enregistrés, 26 ont été exclus car leur dossier était incomplet. Sur les 156 patients restants qui ont été revus, 86 (55,1%) ont eu une évaluation correcte dans le centre, pour 35 (22,4%) patients, elle était incorrecte et les 35 (22,4%) derniers ont été transférés donc pas évalués. A la suite de cette revue, la proportion de patients évalués augmenté de 86 (55,1%) à 150 (96,2%). Le taux de guérison et de succès du traitement ont augmenté de 43,6% et 44,2%, respectivement, à 57,7% et 73,1%, respectivement. Il faut noter que 14 des 35 patients initialement déclarés « transférés ¼ n'ont pas atteint leurs structures de traitement et ont fini par être perdus de vue. CONCLUSION: Cette étude montre qu'il est possible d'évaluer presque tous les patients TB. Une ré-évaluation des résultats du traitement des patients TB a révélé les problèmes des services TB qui doivent être améliorés à l'avenir.

9.
Public Health Action ; 10(1): 21-26, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32368520

RESUMO

SETTING: Four tuberculosis (TB) diagnostic health facilities of the Chongwe District, Zambia. OBJECTIVE: To determine the frequency of bacteriologically confirmed TB patients lost to follow-up (LTFU) before treatment from January to December 2017. DESIGN: This is a retrospective cohort study involving the review of TB registers. Information on presumptive TB patients who tested positive either by smear microscopy or Xpert® MTB/RIF assay was extracted from the laboratory TB registers of the TB diagnostic facilities and cross-matched with the TB treatment registers of TB treatment facilities. RESULTS: Two hundred and seventeen bacteriologically confirmed TB patients were found in the laboratory TB registers. Of these, 145 (67%) were males and seven (3%) were children; 177 (81%) patients were diagnosed using Xpert, while the remaining 40 (19%) were diagnosed using sputum smear microscopy. A total of 71 (33%) were not linked to treatment. Those diagnosed using smear microscopy were 2.5 times (95% CI 1.1-5.3) more likely to be LTFU before treatment than those diagnosed using Xpert. CONCLUSION: About one third of TB patients who were not linked to treatment could potentially extend the duration of bacilli transmission in their communities. National TB control programmes should consider including LTFU patients before treatment in routine monitoring and evaluation.

10.
J Cell Biol ; 142(2): 485-97, 1998 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-9679146

RESUMO

Adducin is a heteromeric protein with subunits containing a COOH-terminal myristoylated alanine-rich C kinase substrate (MARCKS)-related domain that caps and preferentially recruits spectrin to the fast-growing ends of actin filaments. The basic MARCKS-related domain, present in alpha, beta, and gamma adducin subunits, binds calmodulin and contains the major phosphorylation site for protein kinase C (PKC). This report presents the first evidence that phosphorylation of the MARCKS-related domain modifies in vitro and in vivo activities of adducin involving actin and spectrin, and we demonstrate that adducin is a prominent in vivo substrate for PKC or other phorbol 12-myristate 13-acetate (PMA)-activated kinases in multiple cell types, including neurons. PKC phosphorylation of native and recombinant adducin inhibited actin capping measured using pyrene-actin polymerization and abolished activity of adducin in recruiting spectrin to ends and sides of actin filaments. A polyclonal antibody specific to the phosphorylated state of the RTPS-serine, which is the major PKC phosphorylation site in the MARCKS-related domain, was used to evaluate phosphorylation of adducin in cells. Reactivity with phosphoadducin antibody in immunoblots increased twofold in rat hippocampal slices, eight- to ninefold in human embryonal kidney (HEK 293) cells, threefold in MDCK cells, and greater than 10-fold in human erythrocytes after treatments with PMA, but not with forskolin. Thus, the RTPS-serine of adducin is an in vivo phosphorylation site for PKC or other PMA-activated kinases but not for cAMP-dependent protein kinase in a variety of cell types. Physiological consequences of the two PKC phosphorylation sites in the MARCKS-related domain were investigated by stably transfecting MDCK cells with either wild-type or PKC-unphosphorylatable S716A/S726A mutant alpha adducin. The mutant alpha adducin was no longer concentrated at the cell membrane at sites of cell-cell contact, and instead it was distributed as a cytoplasmic punctate pattern. Moreover, the cells expressing the mutant alpha adducin exhibited increased levels of cytoplasmic spectrin, which was colocalized with the mutant alpha adducin in a punctate pattern. Immunofluorescence with the phosphoadducin-specific antibody revealed the RTPS-serine phosphorylation of adducin in postsynaptic areas in the developing rat hippocampus. High levels of the phosphoadducin were detected in the dendritic spines of cultured hippocampal neurons. Spectrin also was a component of dendritic spines, although at distinct sites from the ones containing phosphoadducin. These data demonstrate that adducin is a significant in vivo substrate for PKC or other PMA-activated kinases in a variety of cells, and that phosphorylation of adducin occurs in dendritic spines that are believed to respond to external signals by changes in morphology and reorganization of cytoskeletal structures.


Assuntos
Proteínas de Ligação a Calmodulina/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Proteína Quinase C/metabolismo , Actinas/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Proteínas de Ligação a Calmodulina/química , Proteínas de Ligação a Calmodulina/genética , Bovinos , Células Cultivadas , Citoesqueleto/metabolismo , Primers do DNA/genética , Dendritos/metabolismo , Ativação Enzimática/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Substâncias Macromoleculares , Mutação , Substrato Quinase C Rico em Alanina Miristoilada , Fosforilação , Proteínas/química , Proteínas/metabolismo , Coelhos , Ratos , Espectrina/metabolismo , Especificidade por Substrato , Acetato de Tetradecanoilforbol/farmacologia
11.
J Cell Biol ; 152(2): 237-50, 2001 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-11266442

RESUMO

Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic members of the Bcl-2 family such as Bax and Bak induce apoptogenic cytochrome c release in isolated mitochondria, whereas BH3-only proteins such as Bid and Bik do not directly target the VDAC to induce cytochrome c release. To investigate the biological significance of the VDAC for apoptosis in mammalian cells, we produced two kinds of anti-VDAC antibodies that inhibited VDAC activity. In isolated mitochondria, these antibodies prevented Bax-induced cytochrome c release and loss of the mitochondrial membrane potential (Deltapsi), but not Bid-induced cytochrome c release. When microinjected into cells, these anti-VDAC antibodies, but not control antibodies, also prevented Bax-induced cytochrome c release and apoptosis, whereas the antibodies did not prevent Bid-induced apoptosis, indicating that the VDAC is essential for Bax-induced, but not Bid-induced, apoptogenic mitochondrial changes and apoptotic cell death. In addition, microinjection of these anti-VDAC antibodies significantly inhibited etoposide-, paclitaxel-, and staurosporine-induced apoptosis. Furthermore, we used these antibodies to show that Bax- and Bak-induced lysis of red blood cells was also mediated by the VDAC on plasma membrane. Taken together, our data provide evidence that the VDAC plays an essential role in apoptogenic cytochrome c release and apoptosis in mammalian cells.


Assuntos
Apoptose/fisiologia , Canais Iônicos/fisiologia , Mitocôndrias Hepáticas/fisiologia , Mitocôndrias/fisiologia , Porinas/fisiologia , Sequência de Aminoácidos , Animais , Anticorpos/farmacologia , Anticorpos Monoclonais/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3 , Proteínas de Transporte/metabolismo , Grupo dos Citocromos c/metabolismo , Eritrócitos/fisiologia , Etoposídeo/farmacologia , Células HeLa , Humanos , Mamíferos , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais , Dados de Sequência Molecular , Paclitaxel/farmacologia , Porinas/química , Conformação Proteica , Proteínas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Endogâmicos , Proteínas Recombinantes/metabolismo , Estaurosporina/farmacologia , Transfecção , Canais de Ânion Dependentes de Voltagem , Proteína Killer-Antagonista Homóloga a bcl-2 , Proteína X Associada a bcl-2
12.
J Cell Biol ; 119(5): 1047-61, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1332978

RESUMO

Previously, we found that anti-DDDED antibodies strongly inhibited in vivo nuclear transport of nuclear proteins and that these antibodies recognized a protein of 69 kD (p69) from rat liver nuclear envelopes that showed specific binding activities to the nuclear location sequences (NLSs) of nucleoplasmin and SV-40 large T-antigen. Here we identified this protein as the 70-kD heat shock cognate protein (hsc70) based on its mass, isoelectric point, cellular localization, and partial amino acid sequences. Competition studies indicated that the recombinant hsc70 expressed in Escherichia coli binds to transport competent SV-40 T-antigen NLS more strongly than to the point mutated transport incompetent mutant NLS. To investigate the possible involvement of hsc70 in nuclear transport, we examined the effect of anti-hsc70 rabbit antibodies on the nuclear accumulation of karyophilic proteins. When injected into the cytoplasm of tissue culture cells, anti-hsc70 strongly inhibited the nuclear import of nucleoplasmin, SV-40 T-antigen NLS bearing BSA and histone H1. In contrast, anti-hsc70 IgG did not prevent the diffusion of lysozyme or 17.4-kD FITC-dextran into the nuclei. After injection of these antibodies, cells continued RNA synthesis and were viable. These results indicate that hsc70 interacts with NLS-containing proteins in the cytoplasm before their nuclear import.


Assuntos
Proteínas de Transporte/metabolismo , Compartimento Celular/fisiologia , Núcleo Celular/metabolismo , Proteínas de Choque Térmico HSP70 , Proteínas Nucleares/metabolismo , Fosfoproteínas , Sinais Direcionadores de Proteínas/metabolismo , Sequência de Aminoácidos , Antígenos Virais de Tumores/metabolismo , Ligação Competitiva , Transporte Biológico , Proteínas de Transporte/imunologia , Proteínas de Transporte/isolamento & purificação , Linhagem Celular , Imunofluorescência , Proteínas de Choque Térmico HSC70 , Histonas/metabolismo , Humanos , Ponto Isoelétrico , Dados de Sequência Molecular , Peso Molecular , Proteínas Nucleares/isolamento & purificação , Nucleoplasminas , Proteínas Recombinantes/metabolismo , Vírus 40 dos Símios/metabolismo
13.
J Cell Biol ; 145(2): 347-61, 1999 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-10209029

RESUMO

Adducin is a membrane skeletal protein that binds to actin filaments (F-actin) and thereby promotes the association of spectrin with F-actin to form a spectrin-actin meshwork beneath plasma membranes such as ruffling membranes. Rho-associated kinase (Rho- kinase), which is activated by the small guanosine triphosphatase Rho, phosphorylates alpha-adducin and thereby enhances the F-actin-binding activity of alpha-adducin in vitro. Here we identified the sites of phosphorylation of alpha-adducin by Rho-kinase as Thr445 and Thr480. We prepared antibody that specifically recognized alpha-adducin phosphorylated at Thr445, and found by use of this antibody that Rho-kinase phosphorylated alpha-adducin at Thr445 in COS7 cells in a Rho-dependent manner. Phosphorylated alpha-adducin accumulated in the membrane ruffling area of Madin-Darby canine kidney (MDCK) epithelial cells and the leading edge of scattering cells during the action of tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor (HGF). The microinjection of Botulinum C3 ADP-ribosyl-transferase, dominant negative Rho-kinase, or alpha-adducinT445A,T480A (substitution of Thr445 and Thr480 by Ala) inhibited the TPA-induced membrane ruffling in MDCK cells and wound-induced migration in NRK49F cells. alpha-AdducinT445D,T480D (substitution of Thr445 and Thr480 by Asp), but not alpha-adducinT445A,T480A, counteracted the inhibitory effect of the dominant negative Rho-kinase on the TPA-induced membrane ruffling in MDCK cells. Taken together, these results indicate that Rho-kinase phosphorylates alpha-adducin downstream of Rho in vivo, and that the phosphorylation of adducin by Rho-kinase plays a crucial role in the regulation of membrane ruffling and cell motility.


Assuntos
Proteínas de Ligação a Calmodulina/metabolismo , Citoesqueleto/fisiologia , Proteínas Ativadoras de GTPase , Proteínas Serina-Treonina Quinases/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Ligação a Calmodulina/química , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Membrana Celular/ultraestrutura , Movimento Celular , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/ultraestrutura , Cães , Proteínas de Ligação ao GTP/metabolismo , Fator de Crescimento de Hepatócito/farmacologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Rim , Modelos Biológicos , Dados de Sequência Molecular , Oligopeptídeos/síntese química , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/isolamento & purificação , Fosforilação , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Treonina , Quinases Associadas a rho
15.
Science ; 242(4876): 275-8, 1988 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-3051382

RESUMO

The signal sequence of simian virus 40 (SV40) large T-antigen for translocation into the nucleus is composed of positively charged amino acids Lys-Lys-Lys-Arg-Lys. Rabbit antibodies to a synthetic peptide containing the negatively charged amino acid sequence Asp-Asp-Asp-Glu-Asp were obtained. Indirect immunofluorescence of the antigens recognized by the antibody was punctate at the nuclear rim or the nuclear surface, depending on the plane of focus. The antibody blocked transport of nuclear proteins into the nucleus. The antigens recognized by the antibody were predominantly localized to the nuclear pores.


Assuntos
Núcleo Celular/metabolismo , Proteínas Nucleares/metabolismo , Oligopeptídeos/fisiologia , Fosfoproteínas , Sinais Direcionadores de Proteínas/fisiologia , Sequência de Aminoácidos , Animais , Antígenos/imunologia , Antígenos Transformantes de Poliomavirus , Transporte Biológico , Linhagem Celular , Imunofluorescência , Humanos , Dados de Sequência Molecular , Nucleoplasminas , Oligopeptídeos/imunologia , Ratos
16.
Reprod Med Biol ; 8(3): 107-112, 2009 09.
Artigo em Inglês | MEDLINE | ID: mdl-29662420

RESUMO

Purpose: The fatty acid composition of rabbit blastocysts, blood serum and uterine fluids were analyzed to study embryonic lipid metabolism. Methods: Embryos were collected from Japanese white rabbits and fatty acids were analyzed by gas chromatograph. Results: Total amount of fatty acids in blastocysts was higher than that in serum and uterine fluid. The amount of fatty acids in blastocysts markedly decreased during days 7-13 of pregnancy, and in serum had hovered, but in uterine fluid on day 13 was nine times higher than that on day 7 of pregnancy. Palmitic acid predominates in blastocysts, serum and uterine fluid during this period. Conclusion: Palmitic acid is the most abundant fatty acid in the blastocysts, serum and uterine fluids of rabbit during days 7-13 of pregnancy.

17.
Kyobu Geka ; 62(9): 847-9, 2009 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-19670794

RESUMO

A 58-year-old man was admitted to our hospital complaining of right chest pain. Chest X-ray and chest computed tomography (CT) disclosed a 9 cm mass in the right anterior mediastinum. The tumor demonstrated low signal intensity on T1-weighted images, and high signal intensity on T2-weighted images. It showed delayed enhancement on dynamic magnetic resonance (MR). The operation was performed and the tumor including the infiltrated pericardium and upper and middle lobe of right lung was resected. Histologically, the tumor showed a multinodular proliferation of spindle-shaped or polygonal tumor cells with abundant myxoid background. The histopathological diagnosis of the tumor was myxoid malignant fibrous histiocytoma (MFH). This is a case report of primary myxoid MFH in the anterior mediastinum. The case is rare in its primary site, but it is typical in CT and MR findings.


Assuntos
Histiocitoma Fibroso Maligno/patologia , Neoplasias do Mediastino/patologia , Humanos , Masculino , Pessoa de Meia-Idade
18.
Benef Microbes ; 10(7): 751-758, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31965846

RESUMO

Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients demonstrated to have health benefits, such as decreasing the risk of coronary heart disease, improving parameters associated with metabolic syndrome, and decreasing anxiety symptoms and depression risk. Previous intervention studies indicated the association between blood or tissue PUFA levels and the gut microbiota; however, the details remain incompletely elucidated. We conducted a cross-sectional study to examine the association between PUFAs and the gut microbiota among breast cancer survivors. Adults who had been diagnosed with invasive breast cancer more than one year ago and were not currently undergoing chemotherapy were enrolled. Capillary blood and faecal samples were obtained to assess the blood PUFA levels and gut microbiota compositions. The mean age (n=124) was 58.7 years, and 46% of the participants had a history of chemotherapy. Multiple regression analysis controlling for possible confounders indicated that an increased relative abundance of Actinobacteria was significantly associated with increased levels of docosahexaenoic acid (DHA, beta=0.304, q<0.01). At the genus level, the abundance of Bifidobacterium was positively associated with the level of DHA (beta=0.307, q<0.01). No significant association between omega-6 PUFAs and the relative abundances of gut microbiota members was observed. In addition, analyses stratified by the history of chemotherapy indicated significant associations of PUFA levels with the abundance of some bacterial taxa, including the phylum Actinobacteria (DHA, beta=0.365, q<0.01) and Bacteroidetes (EPA, beta=-0.339, q<0.01) and the genus Bifidobacterium (DHA, beta=0.368, q<0.01) only among participants without a history of chemotherapy. These findings provide the first evidence of positive associations between the abundances of Bifidobacterium among the gut microbiota and the levels of omega-3 PUFAs in the blood. Further studies are required to gain additional insight into these associations in healthy subjects as well as into the causality of the relationship.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer/estatística & dados numéricos , Ácidos Graxos Ômega-3/sangue , Microbioma Gastrointestinal , Idoso , Bactérias/classificação , Bactérias/isolamento & purificação , Neoplasias da Mama/sangue , Neoplasias da Mama/microbiologia , Estudos Transversais , Interpretação Estatística de Dados , Dieta , Fezes/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Artigo em Inglês | MEDLINE | ID: mdl-29628046

RESUMO

The relationship of n-3 polyunsaturated fatty acids (PUFAs) and gut microbiota with brain function has been extensively reported. Here, we review how n-3 polyunsaturated fatty acids affect fear memory processing. n-3 PUFAs may improve dysfunctional fear memory processing via immunomodulation/anti-inflammation, increased BDNF, upregulated adult neurogenesis, modulated signal transduction, and microbiota-gut-brain axis normalization. We emphasize how n-3 PUFAs affect this axis and also focus on the hypothetical effects of PUFAs in fear of cancer recurrence (FCR), the primary psychological unmet need of cancer survivors. Its pathophysiology may be similar to that of post-traumatic stress disorder (PTSD), which involves dysfunctional fear memory processing. Due to fewer adverse effects than psychotropic drugs, nutritional interventions involving n-3 PUFAs should be acceptable for physically vulnerable cancer survivors. We are currently studying the relationship of FCR with n-3 PUFAs and gut microbiota in cancer survivors to provide them with a nutritional intervention that protects against FCR.


Assuntos
Sobreviventes de Câncer/psicologia , Ácidos Graxos Ômega-3/farmacologia , Medo/efeitos dos fármacos , Recidiva Local de Neoplasia/psicologia , Anti-Inflamatórios não Esteroides/farmacologia , Transtornos de Ansiedade/dietoterapia , Transtornos de Ansiedade/microbiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disbiose/dietoterapia , Disbiose/psicologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Memória/efeitos dos fármacos , Neurogênese/efeitos dos fármacos
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