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1.
J Eur Acad Dermatol Venereol ; 38(6): 1166-1178, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38258964

RESUMO

BACKGROUND: During Treponema pallidum (T. pallidum) infection, the host's immune system actively engages in pursuit and elimination of T. pallidum, while T. pallidum skillfully employs various mechanisms to evade immune recognition. Macrophages exhibit incomplete clearance of T. pallidum in vitro and the underlying mechanism of how T. pallidum resists the attack of macrophage remains unclear. OBJECTIVES: To investigate the effect of T. pallidum membrane protein Tp47 on the phagocytosis of macrophages. METHODS: THP-1-derived macrophages were used to investigate the role of Tp47 in the secretion of Prostaglandin E2 (PGE2) in macrophages and the mechanism by which Tp47 induced the production of PGE2, as well as the impact of PGE2 on the macrophage's phagocytosis. RESULTS: Tp47 (1-10 µg/mL) significantly inhibited the phagocytosis of latex beads and T. pallidum in macrophages (p ≤ 0.05). PGE2 production by macrophages could be induced by Tp47, and the phagocytic function of macrophages could be restored using PGE2 antibody. Tp47 produced PGE2 by activating the PERK/NF-κB/COX-2 pathway in macrophages. Inhibitors targeting PERK, NF-κB and COX-2, respectively, reduced the level of PGE2 and restored the phagocytic function of macrophages. CONCLUSION: Tp47-induced PGE2 production via the PERK/NF-κB/COX-2 pathway contributed to macrophage phagocytosis inhibition, which potentially contributes to immune evasion during the T. pallidum infection.


Assuntos
Dinoprostona , Macrófagos , Fagocitose , Treponema pallidum , Humanos , Fagocitose/efeitos dos fármacos , Dinoprostona/metabolismo , Treponema pallidum/imunologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Proteínas de Bactérias/metabolismo , Ciclo-Oxigenase 2/metabolismo
2.
J Eur Acad Dermatol Venereol ; 37(10): 2067-2079, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37247195

RESUMO

BACKGROUND: Glycolysis is a critical pathway in cellular glucose metabolism that provides energy and participates in immune responses. However, whether glycolysis is involved in NOD-like receptor family protein 3 (NLRP3) inflammasome activation and phagocytosis of macrophages in response to Treponema pallidum infection remains unclear. OBJECTIVES: To investigate the role of glycolysis in activating the NLRP3 inflammasome for regulating phagocytosis in macrophages in response to T. pallidum protein Tp47 and its associated mechanisms. METHODS: Interactions between activation of the NLRP3 inflammasome and phagocytosis and the role of glycolysis in Tp47-treated macrophages were investigated through experiments on peritoneal macrophages and human monocytic cell line-derived macrophages. RESULTS: Activation of phagocytosis and NLRP3 inflammasome were observed in Tp47-treated macrophages. Treatment with NLRP3 inhibitor MCC950 or si-NLRP3 attenuated Tp47-induced phagocytosis. Glycolysis and glycolytic capacity were enhanced by Tp47 stimulation in macrophages, and a change in the levels of glycolytic metabolites (phosphoenolpyruvate, citrate and lactate) was induced by Tp47 in macrophages. Inhibition of glycolysis with 2-deoxy-D-glucose, a glycolysis inhibitor, decreased the activation of NLRP3. Expression of M2 isoform of pyruvate kinase (PKM2), an enzyme catalysing a rate-limiting reaction in the glycolytic pathway, was upregulated in Tp47-stimulated macrophages. Inhibition of PKM2 with shikonin or si-PKM2 decreased glycolysis and NLRP3 activation. CONCLUSION: Tp47 promotes phagocytosis in macrophages by activating the NLRP3 inflammasome, which is induced by the enhancement of PKM2-dependent glycolysis.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Treponema pallidum/metabolismo , Proteínas NLR/metabolismo , Macrófagos/metabolismo , Proteínas Recombinantes/metabolismo , Fagocitose , Glicólise
3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(6): 1002-1007, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34814497

RESUMO

Objective: To analysis effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy (combined screening strategy) for screenin the imported patients with COVID-19 in Xiamen. Methods: The study populations were overseas travelers arriving in Xiamen from March 17 to December 31, 2020, and overseas travelers who had quarantine outside Xiamen for less than 21 days from July 18 to December 31, 2020. Data were collected and analyzed on the timing of detection, pathways, and test results of the imported patients with COVID-19 after implementing combined screening strategy. Results: A total of 304 imported patients with COVID-19 were found from 174 628 overseas travelers and 943 overseas travelers from other cities. A total of 163 cases (53.6%) were diagnosed by multitime, multisite intensive nucleic acid testing after positive finding in total antibody testing. Among them, 27 (8.9%) were first positive for nucleic acid in 14 plus 7 day quarantine and 136 were first positive for nucleic acid in 14-day quarantine. Only 8 of these individuals were tested positive for nucleic acid after positive total antibody testing. The other 128 individuals were tested positive for nucleic acid after being negative for average 2.3 times (maximum of 6 times). Aditional 155 cases might be detected by using the combined "14 plus 7 day quarantine" and " nucleic acid plus total antibody testing" strategy compared with "14-day quarantine and nucleic acid testing" strategy, accounting for 51.0% of the total inbound infections. So the combined screening strategy doubled the detection rate for imported patients with COVID-19. No second-generation case caused by overseas travelers had been reported in Xiamen as of February 26, 2021. Conclusions: Xiamen's combined screening strategy can effectively screen the imported patients with COVID-19 who were first positive for nucleic acid after 14 day quarantine. Compared with "14 day quarantine and nucleic acid testing", the combined screening strategy improved detection rate and further reduced the risk of the secondary transmission caused by the imported patients with COVID-19.


Assuntos
COVID-19 , Ácidos Nucleicos , Humanos , Programas de Rastreamento , Quarentena , SARS-CoV-2
4.
J Eur Acad Dermatol Venereol ; 34(9): 2111-2119, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32294266

RESUMO

BACKGROUND: Elucidating the mechanism of the macrophage phagocytic response will improve our knowledge of host defence against Treponema pallidum. OBJECTIVE: To explore whether autophagy promotes T. pallidum phagocytosis and clearance via the NLRP3 inflammasome in macrophages. METHODS: The interactions between autophagy and phagocytosis and the role of NLRP3 in these processes in T. pallidum-treated macrophages were investigated through experiments using human monocytic cell line (THP-1)-derived macrophages. Treponema pallidum clearance after phagocytosis was evaluated by inoculating rabbits with macrophage-treponeme mixtures. RESULTS: Activation of autophagy and phagocytosis in T. pallidum-treated macrophages occurred in a dose- and time-dependent manner. The percentage of spirochete-positive macrophages (22.34% vs. 70.93%, P < 0.001) and spirochete internalization (MFI: 9.62 vs. 20.33, P < 0.001) were notably reduced by silencing Beclin1. Inoculation of macrophage-treponeme mixtures into rabbits showed a 3.00-day delay in lesion development (17.55 ± 3.73 vs. 14.55 ± 1.99 days) and decreased lesion numbers [11 (36.7%) vs. 20 (66.7%) of 30; χ2  = 5.406, P = 0.020] in the control compared with the si-Beclin1 group. Furthermore, silencing NLRP3 decreased the mRNA and protein levels of Beclin-1 and LC3B [mRNA: 49.86% and 43.02%; protein: 22.31% and 24.24%, respectively, differing significantly from the control group (P < 0.001)] and reduced the percentage of spirochete-positive macrophages (30.29% vs. 70.53%, P < 0.001) and spirochete internalization (MFI: 9.82 vs. 19.33, P < 0.001). CONCLUSION: Treponema pallidum induces autophagy in macrophages to promote phagocytosis and clearance. The NLRP3 inflammasome modulates autophagy and phagocytosis in vitro. These data may be useful for understanding the host-pathogen relationship and establish the groundwork for strategies to combat syphilis.


Assuntos
Inflamassomos , Treponema pallidum , Animais , Autofagia , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fagocitose , Coelhos
5.
J Eur Acad Dermatol Venereol ; 33(10): 1958-1970, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31166625

RESUMO

BACKGROUND: Although angiogenesis is an obvious pathological manifestation in the pathogenesis of syphilis, little is known about the underlying mechanisms of angiogenesis induced by reactions to Treponema pallidum antigens. OBJECTIVE: In this study, we sought to determine the role of recombinant T. pallidum Tp47 in promoting angiogenesis in endothelial cells and the related mechanism. METHODS: Evaluation of the pro-angiogenic activity of recombinant T. pallidum Tp47 in human umbilical vein endothelial cells (HUVECs) was assessed, and the balance of matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) and the mechanisms underlying the involvement of Akt/mTOR/S6 pathways in this process were explored. RESULTS: Under stimulation by Tp47, HUVECs exhibited obvious proliferation, migration and tube formation. In addition, the apparent promotion of angiogenesis by Tp47 was observed using a zebrafish embryo model. During angiogenesis, the levels of MMP-1 and MMP-10 were significantly elevated, whereas those of TIMP-1 and TIMP-2 did not change. In addition, after transfection with siRNAMMP-1 and siRNAMMP-10, migration and tube formation were significantly inhibited. Akt/mTOR/S6 signalling was found to be involved in upregulating MMP-1 and MMP-10 expression, and the sequential blockade of steps in the pathways effectively prevented Tp47-induced angiogenesis. CONCLUSION: The results reveal the underlying mechanism of angiogenesis promoted by Tp47, namely, upregulating MMP-1 and MMP-10 expression to disrupt the MMP/TIMP balance through the Akt/mTOR/S6 pathway. These findings contribute to our understanding of the pathophysiology of syphilis.


Assuntos
Indutores da Angiogênese/farmacologia , Neovascularização Patológica/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , beta-Lactamases/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 10 da Matriz/genética , Metaloproteinase 10 da Matriz/metabolismo , Neovascularização Patológica/genética , Neovascularização Fisiológica/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Peixe-Zebra/embriologia
6.
J Eur Acad Dermatol Venereol ; 33(7): 1378-1385, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30803039

RESUMO

BACKGROUND: Global metabolomics analysis can provide substantial information on energy metabolism, physiology, possible diagnostic biomarkers and intervention strategies for pathogens. OBJECTIVE: To gain a better understanding of the mechanisms of syphilis and analysis of serum metabolite profiles in syphilis patients. METHODS: We conducted an untargeted metabolomics analysis of serum from 20 syphilis patients and 20 healthy controls. RESULTS: A total of 2890 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Distinct differential metabolites were identified by principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis. Furthermore, five metabolites were identified as significantly different by Student's t-test, including trimethylamine N-oxide, l-arginine, lysoPC(18:0), betaine and acetylcarnitine. KEGG analysis showed that these differential metabolites were in various pathways, including Chagas disease, fatty acid biosynthesis, primary bile acid biosynthesis, Salmonella infection, ABC transporters, glycerophospholipid metabolism and choline metabolism. Among them, trimethylamine N-oxide was 3.922 times in patients with syphilis than healthy controls. CONCLUSION: Trimethylamine N-oxide may be used as an indicator to distinguish between syphilis patients and healthy controls. The changes in these metabolites suggest that Treponema pallidum affects the normal metabolic activity of host cells, providing some clues for elucidating the pathogenesis of T. pallidum.


Assuntos
Acetilcarnitina/sangue , Arginina/sangue , Betaína/sangue , Metilaminas/sangue , Sífilis/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Redes e Vias Metabólicas , Metabolômica , Pessoa de Meia-Idade , Análise de Componente Principal , Sífilis/microbiologia
7.
Orthop Traumatol Surg Res ; 104(6): 797-801, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29654932

RESUMO

INTRODUCTION: The glenoid track concept was used to confirm the engaging Hill-Sachs lesion (HSL) as a risk factor for recurrent instability following arthroscopic Bankart repair (ABR). However, the post-operative condition of soft tissue in vivo was not comparable to that designed in the intact condition in vitro in the original study of the glenoid track concept. Herein, the possibility of engagement may be underestimated. HYPOTHESIS: A threshold of the Hill-Sachs interval to glenoid track width ratio (H/G ratio) that is related to recurrent instability after ABR could be found, in order to adjust the original glenoid track concept. PATIENTS AND METHODS: Patients who underwent ABR with minimum 24-months follow-up were reviewed retrospectively. The primary outcome was evaluated with the recurrent instability. The H/G ratio of individual patients was used to calculate the sensitivity, specificity, and a receiver operating characteristic (ROC) curve, which aimed to establish a H/G ratio threshold related to recurrent instability after ABR. RESULTS: From June 2005 to December 2013, 160 patients with a mean age of 27.7years were enrolled. The mean follow-up period was 77.2 months. The ROC curve indicated that H/G ratio≥0.7 had the sensitivity and specificity of 0.74 and 0.71, respectively, in predicting recurrent instability. On univariate logistic regression analysis, the H/G ratio≥0.7 was a significant predictor of higher risk for recurrent instability (p<0.001). DISCUSSION: H/G ratio seems to be a reliable parameter for predicting recurrent instability. H/G ratio≥0.7 may be considered as a positive predictor for recurrent instability after ABR. LEVEL OF EVIDENCE: Level IV: retrospective diagnostic study.


Assuntos
Lesões de Bankart/diagnóstico por imagem , Lesões de Bankart/cirurgia , Cavidade Glenoide/diagnóstico por imagem , Instabilidade Articular/cirurgia , Articulação do Ombro/cirurgia , Adolescente , Adulto , Artroscopia , Lesões de Bankart/complicações , Feminino , Seguimentos , Humanos , Instabilidade Articular/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Curva ROC , Radiografia , Recidiva , Estudos Retrospectivos , Adulto Jovem
8.
Osteoporos Int ; 27(7): 2281-2290, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27139906

RESUMO

UNLABELLED: In a large cohort of older women, we investigated the relationships that different forms of vitamin E may have with bone turnover markers and bone mineral density (BMD). We found a suggestive positive association between serum alpha-tocopherol and BMD at the femoral neck, but no other clinically relevant observations. INTRODUCTION: Vitamin E has anti-oxidant and anti-inflammatory properties hypothesized to benefit bone, but limited studies exist regarding its homologues. We examined circulating and dietary α- and γ-tocopherols with bone turnover markers (BTMs) and bone mineral density (BMD), and the role of inflammation in this relationship. METHODS: We performed two cross-sectional analyses from two visits (V2, 1997-1999, n = 3883; V3, 2007-2011, n = 2130) of the Aberdeen Prospective Osteoporosis Screening Study. Dietary and supplement intakes by food frequency questionnaire were assessed at both visits. V2 BTMs (urinary free pyridinoline and deoxypyridinoline, serum N-terminal propeptide of type 1 collagen) and V3 serum α- and γ-tocopherols, inflammatory markers (interleukin-6 [IL-6], serum amyloid A [SAA], high-sensitivity C-reactive protein [hs-CRP], E-selectin) and dual X-ray absorptiometry BMD at the femoral neck and lumbar spine were collected. Food sources of tocopherol homologues and diet-serum correlations were determined. The relationships between dietary tocopherols and BTMs (V2), and dietary and serum tocopherols with BMD (V3) were examined by multivariable regression (adjusting for age, cholesterol, inflammatory markers, carotenoids, body mass index, physical activity level, alcohol intake, smoking status and national deprivation category). RESULTS: Serum γ-tocopherol was associated with increasing concentrations of hs-CRP, SAA and E-selectin (P-trend all <0.0001), while α-tocopherol was associated with decreasing concentrations of IL-6 and hs-CRP (P-trend all <0.001). Controlling for covariates, serum α-tocopherol was positively associated with BMD at the femoral neck (ß = 0.002, P = 0.04) among those not reporting vitamin E supplementation. CONCLUSION: We did not find biologically meaningful results between dietary and tocopherol homologues with BTMs or BMD.


Assuntos
Densidade Óssea , Remodelação Óssea , alfa-Tocoferol/sangue , gama-Tocoferol/sangue , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Perimenopausa , Pós-Menopausa , Estudos Prospectivos , Vitamina E
9.
Epidemiol Infect ; 144(6): 1165-74, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26467944

RESUMO

This study aimed to comprehensively evaluate factors that influence the likelihood of syphilis infection from risk-taking behaviours and medical conditions. A retrospective case-control study was conducted by enrolling 664 syphilis inpatients (excluding 11 congenital syphilis patients) and 800 sex- and age-matched controls. Medical histories, clinical data and patient interview data were collected and subjected to logistic regression analyses. The prevalence of syphilis in the study population was 3·9% (675/17,304). By univariate analysis, syphilis infection was associated with migration between cities, marital status, smoking, reproductive history, hypertension, elevated blood urea nitrogen (BUN) and infection with hepatitis B virus (HBV) (P < 0·05). A high rate of syphilis-HBV co-infection was observed in HIV-negative patients and further research revealed an association between syphilis and specific HBV serological reactivity. Syphilis was also associated with the frequency, duration and status of tobacco use. Multivariate analysis indicated that syphilis infection was independently associated with migration between cities [adjusted odds ratio (aOR) 1·368, 95% confidence interval (CI) 1·048-1·785], current smoking (aOR 1·607, 95% CI 1·177-2·195), elevated BUN (aOR 1·782, 95% CI 1·188-2·673) and some serological patterns of HBV infection. To prevent the spread of infectious diseases, inpatients and blood donors should be tested for HIV, syphilis, HBV and HCV simultaneously.


Assuntos
Sífilis/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Assunção de Riscos , Adulto Jovem
10.
Environ Technol ; 36(23): 2987-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25241807

RESUMO

In the present study, silicon carbide (SiC) recovered from silicon sludge wastes is used as catalysts for photocatalytic reduction of CO2. By X-ray diffraction, it is clear that the main components in the silicon sludge wastes are silicon and SiC. The grain size of the SiC separated from the sludge waste is in the range of 10-20 µm in diameter (observed by scanning electron microscopy). By solid state nuclear magnetic resonance, it is found that α-SiC is the main crystallite in the purified SiC. The α-SiC has the band-gap of 3.0 eV. To yield C1-C2chemicals from photocatalytic reduction of CO2, hydrogen is provided by simultaneous photocatalytic splitting of H2O. Under the light (253-2000 nm) illumination, 12.03 and 1.22 µmol/h g cat of formic and acetic acids, respectively, can be yielded.


Assuntos
Compostos Inorgânicos de Carbono/química , Dióxido de Carbono/química , Compostos de Silício/química , Ácido Acético/química , Poluição do Ar/prevenção & controle , Catálise , Formiatos/química , Hidrogênio/química , Resíduos Industriais , Luz , Oxirredução , Reciclagem/métodos , Esgotos , Silício , Água/química
11.
Eur J Neurol ; 17(10): 1277-84, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20831774

RESUMO

BACKGROUND: Aneurysms located at non-branching sites, protruding from the dorsal wall of the supraclinoid internal carotid artery (ICA) with rapid configurational changes, were retrospectively reviewed in effort to identify and characterize these high-risk aneurysms. METHODS: A total of 447 patients with 491 intracranial aneurysms were treated from March 2005 to August 2008, and of these, eight patients had ICA dorsal wall aneurysms. Four of them suffered subarachnoid hemorrhage (SAH), and all had aneurysms undergoing rapid configuration changes during the treatment course. Digital subtraction cerebral angiography (DSA) performed soon after the SAH events. Data analyzed were patient age, sex, Hunt and Kosnik grade, time interval from first DSA to second DSA, aneurysm treatment, and modified Rankin scale score after treatment for 3 months. Success or failure of therapeutic management was examined among the patients. RESULTS: Digital subtraction cerebral angiography showed only lesions with small bulges in the dorsal walls of the ICAs. However, the patients underwent DSA again for re-bleeding or for post-treatment follow-up, confirming the SAH source. ICA dorsal wall aneurysms with rapid growth and configurational changes were found on subsequent DSA studies. CONCLUSIONS: Among the four patients, ICA dorsal wall aneurysms underwent rapid growth with configurational change from a blister type to a saccular type despite different management. ICA trapping including the lesion segment can be considered as the first treatment option if the balloon occlusion test (BOT) is successful. If a BOT is not tolerated by the patient, extracranial-intracranial bypass revascularization surgery with endovascular ICA occlusion is another treatment option.


Assuntos
Dissecação da Artéria Carótida Interna/diagnóstico , Dissecação da Artéria Carótida Interna/cirurgia , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Dissecação da Artéria Carótida Interna/patologia , Progressão da Doença , Feminino , Humanos , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/instrumentação , Estudos Retrospectivos , Procedimentos Cirúrgicos Vasculares/instrumentação
12.
Int J Immunogenet ; 36(4): 207-11, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19476482

RESUMO

We report here a novel HLA-B allele, B*2740, discovered in Taiwanese volunteer marrow donors. The new sequence has nucleotide variation at position 527 (T-->A) as compared to B*2708. The nucleotide change caused an amino acid substitution from valine (V) to glutamic acid (E) at codon 152. Since B*2740 carries sequence confers to HLA-Bw6 public epitope we believe that this novel B*27 allele might have been generated from a gene conversion involving a Bw4-specific allele (probably B*2704) and a Bw6-specific allele.


Assuntos
Conversão Gênica/genética , Frequência do Gene/genética , Antígeno HLA-B27/genética , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Sequência de Bases , Medula Óssea/metabolismo , Cromossomos Humanos Par 6/genética , Éxons/genética , Ácido Glutâmico/genética , Humanos , Doadores Vivos , Dados de Sequência Molecular , Alinhamento de Sequência , Taiwan , Valina/genética
13.
Cancer Gene Ther ; 16(4): 338-50, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18989352

RESUMO

We have investigated the therapeutic potential of a prototypic melanoma vaccine based on recombinant adenovirus expressing human dopachrome tautomerase in the B16F10 murine melanoma model. We found that in the presence of a tumor, the magnitude of T-cell immunity evoked by the vaccine was significantly reduced. This impairment was compounded by defects in cytokine production and degranulation within the tumor-infiltrating lymphocytes (TILs). We showed that the combination of vaccination with high-dose cyclophosphamide was able to skew the response toward the target antigen and enhanced both the quantity and quality of antigen-specific CD8+ and CD4+ T-cell responses in tumor-bearing mice, which resulted in the inhibition of tumor growth. Furthermore, when tumor-specific antigens were targeted by the vaccine, the combination therapy could actually produce tumor regression, which appeared to result from the high frequency of antigen-specific T cells. These data show that recombinant adenovirus vaccines are compatible with conventional high-dose chemotherapy and that the combined treatment results in improved therapeutic outcomes relative to either agent individually.


Assuntos
Adenoviridae/genética , Vacinas Anticâncer/uso terapêutico , Ciclofosfamida/administração & dosagem , Melanoma Experimental/terapia , Vacinas de DNA/uso terapêutico , Animais , Antineoplásicos Alquilantes/administração & dosagem , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Vetores Genéticos , Humanos , Imunidade Celular/efeitos dos fármacos , Oxirredutases Intramoleculares/biossíntese , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/imunologia , Melanoma Experimental/imunologia , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Camundongos , Transplante de Neoplasias , Oxirredutases/biossíntese , Oxirredutases/genética , Oxirredutases/imunologia , Resultado do Tratamento
14.
Minim Invasive Neurosurg ; 51(5): 280-4, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18855293

RESUMO

Spinal metastatic tumor is a common problem and represents a challenging problem in oncology practice. Patients with osteolytic metastases often suffer from intractable local and/or radicular pain. Percutaneous vertebroplasty is a minimally invasive, radiologically guided procedure whereby bone cement is injected into structurally weakened vertebrae to provide immediate biomechanical stability. Vertebroplasty is also used to relieve pain by stabilizing metastatically compromised vertebrae that are at risk of pathological burst fracture. In this retrospective study, a total of 57 patients (78 vertebrae) with spinal metastatic tumor were treated with PMMA vertebroplasty. The mean value of the visual analogue scale (VAS) was 8.1 +/- 0.67 preoperatively, and significantly decreased to 3.8 +/- 1.9 (1-8, p < 0.015) one day after vertebroplasty. The mean VAS value 6 months after vertebroplsty was 2.8 +/- 2.0 (p < 0.001). Mean injected bone cement amount in our study is 5.16 +/- 1.6 mL. The complication rate is about 21.8%, bone cement extravasation without neurological deficit is the most common complication. No new or adjacent vertebral fracture has occurred in more than 2 years follow-up. Percutaneous vertebroplasty is a minimally invasive procedure that offers a remarkable advantage of effective and immediate pain relief with few complications.


Assuntos
Dor nas Costas/cirurgia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/secundário , Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor nas Costas/etiologia , Dor nas Costas/patologia , Cimentos Ósseos/uso terapêutico , Extravasamento de Materiais Terapêuticos e Diagnósticos/epidemiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Medição da Dor , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios , Radiografia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/patologia , Fraturas da Coluna Vertebral/cirurgia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Resultado do Tratamento , Vertebroplastia/instrumentação
15.
Radiat Res ; 157(1): 76-91, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11754645

RESUMO

The radiation risk to astronauts has always been based on measurements using passive thermoluminescent dosimeters (TLDs). The skin dose is converted to dose equivalent using an average radiation quality factor based on model calculations. The radiological risk estimates, however, are based on organ and tissue doses. This paper describes results from the first space flight (STS-91, 51.65 degrees inclination and approximately 380 km altitude) of a fully instrumented Alderson Rando phantom torso (with head) to relate the skin dose to organ doses. Spatial distributions of absorbed dose in 34 1-inch-thick sections measured using TLDs are described. There is about a 30% change in dose as one moves from the front to the back of the phantom body. Small active dosimeters were developed specifically to provide time-resolved measurements of absorbed dose rates and quality factors at five organ locations (brain, thyroid, heart/lung, stomach and colon) inside the phantom. Using these dosimeters, it was possible to separate the trapped-proton and the galactic cosmic radiation components of the doses. A tissue-equivalent proportional counter (TEPC) and a charged-particle directional spectrometer (CPDS) were flown next to the phantom torso to provide data on the incident internal radiation environment. Accurate models of the shielding distributions at the site of the TEPC, the CPDS and a scalable Computerized Anatomical Male (CAM) model of the phantom torso were developed. These measurements provided a comprehensive data set to map the dose distribution inside a human phantom, and to assess the accuracy and validity of radiation transport models throughout the human body. The results show that for the conditions in the International Space Station (ISS) orbit during periods near the solar minimum, the ratio of the blood-forming organ dose rate to the skin absorbed dose rate is about 80%, and the ratio of the dose equivalents is almost one. The results show that the GCR model dose-rate predictions are 20% lower than the observations. Assuming that the trapped-belt models lead to a correct orbit-averaged energy spectrum, the measurements of dose rates inside the phantom cannot be fully understood. Passive measurements using 6Li- and 7Li-based detectors on the astronauts and inside the brain and thyroid of the phantom show the presence of a significant contribution due to thermal neutrons, an area requiring additional study.


Assuntos
Radiação Cósmica , Nêutrons , Imagens de Fantasmas , Doses de Radiação , Voo Espacial , Dosimetria Termoluminescente , Abdome/efeitos da radiação , Astronautas , Medula Óssea/efeitos da radiação , Encéfalo/efeitos da radiação , Desenho de Equipamento , Humanos , Lítio , Masculino , Modelos Teóricos , Especificidade de Órgãos , Prótons , Proteção Radiológica , Medição de Risco , Pele/efeitos da radiação , Astronave , Medula Espinal/efeitos da radiação , Testículo/efeitos da radiação , Tórax/efeitos da radiação , Glândula Tireoide/efeitos da radiação , Vísceras/efeitos da radiação
16.
Environ Technol ; 22(6): 647-51, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11482384

RESUMO

An ozone-induced agitated reactor has been found to be very effective in degrading industrial wastewater. However, the cost of the ozone generation as well as its short residence time in reactors has restricted its application in a commercial scale. An innovated gas-induced draft tube installed inside a conventional agitated reactor was proved to effectively retain the ozone in a reactor. The setup was demonstrated to significantly promote the ozone utilization rate up to 96% from the conventional rate of 60% above the onset speed. This work investigates the mixing mechanism of an innovated gas-induced reactor for the future scale-up design by using the technique of computational fluid dynamics. A three-dimensional flow model was proposed to compute the liquid-gas free surface as well as the flow patterns inside the reactor. The turbulent effects generated by two 45 degrees pitch-blade turbines were considered and the two phases mixing phenomena were also manipulated by the Eulerian-Eulerian techniques. The consistency of the free surface profiles and the fluid flow patterns proved a good agreement between computational results and the experimental observation.


Assuntos
Resíduos Industriais , Modelos Teóricos , Oxidantes/química , Ozônio/química , Eliminação de Resíduos Líquidos/métodos , Poluição Ambiental/prevenção & controle , Desenho de Equipamento , Movimentos da Água
17.
Zhonghua Yi Xue Za Zhi (Taipei) ; 63(10): 751-7, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11076432

RESUMO

BACKGROUND: The outcome of congenital diaphragmatic hernia (CDH) remains poor despite recent advances in neonatal care. This study was designed to evaluate the role of sonography in predicting the outcome of CDH. METHODS: Pregnancies with CDH were studied. Fetal survival, morbidity, combined anomalies and mortality were recorded. Seven parameters were recorded, including the presence of hydramnios, side of herniation, cardiac deviation, stomach presence, gestational age at the time of finding the CDH and time of postpartum herniorrhaphy. The predictive values of these parameters for fetal outcome were analyzed. RESULTS: A total of 31 pregnancies were studied. There were 11 cases (35.5%) of termination, seven cases (22.6%) of perinatal death, four cases (12.9%) of late death and nine cases of survival (29%). The survivor group included four cases (44.4%) of complete recovery and five cases (55.6%) with persistent morbidity. There were 15 cases of simple CDH including eight cases of cardiac anomalies (ventricular-septal defect, atrial-septal defect, patent ductus arteriosus and ventricular dilatation). There were eight cases with severe anomalies (3 with trisomy 18, 2 with Cantrell's pentalogy, 1 with trisomy 13, 1 with cystic hygroma and one with Tetralogy Fallot). Among the seven parameters studied, gestational age at the time of finding the CDH and hydramnios were related to fetal survival. CONCLUSIONS: Sonography assists in predicting the postnatal outcome of CDH. Diagnosis of CDH at less than 25 weeks' gestation and the existence of hydramnios are associated with higher mortality. Postnatal therapy and prenatal surgical intervention are necessary to salvage fetuses in the presence of these two situations. The survival rate of infants with CDH was 45%. Of these, 55.6% had persistent morbidity. Prenatal counseling should reflect this.


Assuntos
Hérnia Diafragmática/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas , Ultrassonografia Pré-Natal , Feminino , Humanos , Gravidez , Resultado da Gravidez
18.
Adv Space Res ; 25(10): 2123-30, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11542865

RESUMO

For a better understanding of oncogenic cell transformation by ionizing radiation, we conducted experiments with ultrasoft X rays and low energy alpha particles. Confluent C3H10T1/2 cells were irradiated by Al-K (1.5 keV) X rays or alpha particles from plutonium through a thin mylar sheet, on which the cells attached and grew. Our results indicated that Al-K X rays were more effective in causing cell inactivation and oncogenic transformation than 60Co gamma rays but less effective than 1.0 and 3.7 MeV alpha particles. There was no significant difference between 1.0 and 3.7 MeV alpha particles in transforming cells although the latter were slightly more effective than the former in producing lethal effect. These results indicated that track structure is important in causing biological effects by ionizing radiation.


Assuntos
Partículas alfa , Transformação Celular Neoplásica , Eficiência Biológica Relativa , Raios X , Alumínio , Animais , Linhagem Celular Transformada , Sobrevivência Celular , Radioisótopos de Cobalto , Relação Dose-Resposta à Radiação , Fibroblastos , Raios gama , Camundongos , Camundongos Endogâmicos C3H , Doses de Radiação
19.
Artigo em Chinês | MEDLINE | ID: mdl-12024590

RESUMO

OBJECTIVE: To compare the permeability and incidence rate of complication of arteriovenous internal fistula made by autogenous, homologous, and artificial Teflon blood vessels. METHODS: Two hundred and forty one cases with arteriovenous internal fistula made by autogenous, homologous, and artificial Teflon blood vessels were followed up to compare the permeability and incidence rate of complication at 6 months, 1 year, 3 years, and 5 years. RESULTS: The incidence rate of complication of autogenous blood vessels was lowest, it had no statistical differences compared with arteriovenous internal fistula made by homologous blood vessels. The permeability of arteriovenous internal fistula made by homologous blood vessels was highest, and it had no statistical differences compared with autogenous blood vessels. The permeability of arteriovenous internal fistula made by artificial Teflon blood vessels was lowest, but the incidence rate of complication was highest, and it had significantly statistical differences compared with arteriovenous internal fistula made by autogenous blood vessels (P < 0.01). CONCLUSION: Arteriovenous internal fistulas made by autogenous and homologous blood vessels have high permeability and low incidence rate of complication, they are superior to the arteriovenous internal fistula made by artificial Teflon blood vessels.


Assuntos
Fístula Arteriovenosa/cirurgia , Implante de Prótese Vascular , Falência Renal Crônica/terapia , Adolescente , Adulto , Idoso , Braço/irrigação sanguínea , Feminino , Glomerulonefrite/complicações , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Politetrafluoretileno , Próteses e Implantes , Artéria Radial/cirurgia , Diálise Renal/métodos
20.
Radiat Meas ; 30(3): 383-92, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11543142

RESUMO

This paper briefly reviews proton radiobiology. Clinical applications of protons produced by accelerators have led to a significant biological literature that contributes to our goal of estimating the proton shielding requirements for human interplanetary missions. Protons are primarily a low-LET radiation with biological effects much like gamma radiation. There are however data indicating enhanced biological effectiveness for small doses of very low energy (<10 MeV) stopping protons, and some limited data for extremely high energy protons (>0.5 GeV).


Assuntos
Fenômenos Fisiológicos Celulares/efeitos da radiação , Prótons , Radiobiologia , Animais , Catarata/etiologia , Aberrações Cromossômicas , Relação Dose-Resposta à Radiação , Feminino , Fibroblastos/efeitos da radiação , Raios gama , Humanos , Transferência Linear de Energia , Linfócitos/efeitos da radiação , Masculino , Mutação , Neoplasias Induzidas por Radiação , Eficiência Biológica Relativa , Sementes/efeitos da radiação
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