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1.
Phys Rev Lett ; 126(21): 216405, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34114834

RESUMO

Non-Hermiticity gives rise to unique topological phases without Hermitian analogs. However, the effective field theory has yet to be established. Here, we develop a field-theoretical description of the intrinsic non-Hermitian topological phases. Because of the dissipative and nonequilibrium nature of non-Hermiticity, our theory is formulated solely in terms of spatial degrees of freedom, which contrasts with the conventional theory defined in spacetime. Our theory provides a universal understanding of non-Hermitian topological phenomena such as the unidirectional transport in one dimension and the chiral magnetic skin effect in three dimensions. Furthermore, it systematically predicts new physics; we illustrate this by revealing transport phenomena and skin effects in two dimensions induced by a perpendicular spatial texture. From the field-theoretical perspective, the non-Hermitian skin effect, i.e., the anomalous localization due to non-Hermiticity, is shown to be a signature of an anomaly.

2.
J Infect Chemother ; 27(3): 450-454, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33218876

RESUMO

INTRODUCTION: ID NOW™ Influenza A & B 2 (ID NOW 2) is a rapid molecular assay that combines two characteristics, namely the rapidness of rapid antigen detection test (RADT) and the high sensitivity of molecular assay. METHODS: The clinical performance of ID NOW 2 compared with real-time RT-PCR was evaluated in adults. RESULTS: The sensitivity of ID NOW 2 over multiple seasons from 2016/2017 to 2019/2020 was 97.3% (95% CI: 90.7-99.7) for Type A, 100% (95% CI: 81.9-100) for Type B, and 97.8% (95% CI: 92.2-99.7) for influenza (Type A + Type B), and it was significantly higher than the sensitivity of RADT, which was 80.0% (95% CI: 69.2-88.4) for Type A, 73.3% (95% CI: 44.9-92.2) for Type B, and 78.9% (95% CI: 69.0-86.8) for influenza. The sensitivity of RADT tended to be lower in patients in the particularly early period, within 12 h from disease onset; however, the sensitivity of ID NOW 2 remained high, increasing the difference between the sensitivity of RADT and ID NOW 2. The viral loads were low within 12 h from onset, and it was considered this affected the sensitivity of RADT due to its low analytical sensitivity. The specificity of ID NOW 2 was 98% or greater in all groups. CONCLUSIONS: Since ID NOW 2 has a high sensitivity and specificity in adults, it is anticipated to be used in clinical practice, particularly in patients who require early and accurate diagnosis.


Assuntos
Vírus da Influenza A , Influenza Humana , Adulto , Clorofenóis , Humanos , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Sensibilidade e Especificidade
3.
Phys Rev Lett ; 124(8): 086801, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32167324

RESUMO

A unique feature of non-Hermitian systems is the skin effect, which is the extreme sensitivity to the boundary conditions. Here, we reveal that the skin effect originates from intrinsic non-Hermitian topology. Such a topological origin not merely explains the universal feature of the known skin effect, but also leads to new types of the skin effects-symmetry-protected skin effects. In particular, we discover the Z_{2} skin effect protected by time-reversal symmetry. On the basis of topological classification, we also discuss possible other skin effects in arbitrary dimensions. Our work provides a unified understanding about the bulk-boundary correspondence and the skin effects in non-Hermitian systems.

4.
J Infect Chemother ; 26(2): 216-221, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31558351

RESUMO

In this study, we evaluated the performance of ID NOW Influenza A & B 2 (ID NOW 2), a rapid molecular point-of-care test for influenza within 13 min, in comparison with currently available tests. A total of 254 nasopharyngeal swabs (NPS) and 271 nasopharyngeal aspirates (NPA) collected from 373 children and 152 adults with influenza-like illness were tested using ID NOW 2, viral culture, rapid antigen detection test, and loop-mediated isothermal amplification test to evaluate the sensitivity and specificity compared with real-time reverse transcription polymerase chain reaction as the reference method. The sensitivities of ID NOW 2 for influenza A were 95.9% and 95.7% in NPS and NPA, respectively, and for influenza B were 100% and 98.7% in NPS and NPA, respectively. The specificity was 100% for both influenza A and influenza B in NPS and NPA. Sensitivity of each test method reflected the difference of analytical sensitivity among the tests, and ID NOW 2 was not affected by time after illness onset and patient age. In conclusion, ID NOW 2 demonstrated a high sensitivity and specificity that is useful for diagnosis of influenza in the clinical setting and infection control.


Assuntos
Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/isolamento & purificação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Adulto Jovem
5.
Phys Rev Lett ; 120(9): 096601, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29547339

RESUMO

Understanding the interplay between the topological nature and the symmetry property of interacting systems has been a central matter of condensed matter physics in recent years. In this Letter, we establish nonperturbative constraints on the quantized Hall conductance of many-body systems with arbitrary interactions. Our results allow one to readily determine the many-body Chern number modulo a certain integer without performing any integrations, solely based on the rotation eigenvalues and the average particle density of the many-body ground state.

6.
Phys Rev Lett ; 118(21): 216402, 2017 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-28598638

RESUMO

We define and compute many-body topological invariants of interacting fermionic symmetry-protected topological phases, protected by an orientation-reversing symmetry, such as time-reversal or reflection symmetry. The topological invariants are given by partition functions obtained by a path integral on unoriented spacetime which, as we show, can be computed for a given ground state wave function by considering a nonlocal operation, "partial" reflection or transpose. As an application of our scheme, we study the Z_{8} and Z_{16} classification of topological superconductors in one and three dimensions.

7.
Phys Rev Lett ; 110(7): 076804, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25166392

RESUMO

The relation between bulk topological invariants and experimentally observable physical quantities is a fundamental property of topological insulators and superconductors. In the case of chiral symmetric systems in odd spatial dimensions such as time-reversal invariant topological superconductors and topological insulators with sublattice symmetry, this relation has not been well understood. We clarify that the winding number which characterizes the bulk Z nontriviality of these systems can appear in electromagnetic and thermal responses in a certain class of heterostructure systems. It is also found that the Z nontriviality can be detected in the bulk "chiral polarization," which is induced by magnetoelectric effects.

8.
Int J Cancer ; 122(10): 2266-73, 2008 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-18224682

RESUMO

In the present study, we investigated the mechanisms by which anti-endoglin (EDG; CD105) monoclonal antibodies (mAbs) suppress angiogenesis and tumor growth. Antihuman EDG mAb SN6j specifically bound to murine endothelial cells and was internalized into the cells in vitro. SN6j effectively suppressed angiogenesis in mice in the Matrigel plug assay. We found that SN6j is more effective for tumor suppression in immunocompetent mice than in SCID mice. We hypothesized that T cell immunity is important for effective antitumor efficacy of SN6j in vivo. To test this hypothesis, we investigated effects of CpG oligodeoxynucleotides (ODN) and depletion of CD4(+) T cells and/or CD8(+) T cells on antitumor efficacy of SN6j in mice. Systemic (i.v.) administration of a relatively small dose (0.6 mug/g body weight/dose) of SN6j suppressed growth of established s.c. tumors of colon-26 in BALB/c mice and improved survival of the tumor-bearing mice. Addition of CpG ODN to SN6j synergistically enhanced antitumor efficacy of SN6j. In contrast, such enhancing effects of CpG ODN were not detected in SCID mice. Antitumor efficacy of SN6j in BALB/c mice was abrogated when CD4(+) T cells and/or CD8(+) T cells were depleted; effect of CD8(+) T cell depletion was stronger. Interestingly, CD4-depletion decreased tumor growth while CD8-depletion enhanced tumor growth in the absence of SN6j. SN6j induced apoptosis in human umbilical vein endothelial cells in a dose-dependent manner which indicates an additional mechanism of antiangiogenesis by SN6j. (c) 2008 Wiley-Liss, Inc.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD/imunologia , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/terapia , Neoplasias Mamárias Experimentais/irrigação sanguínea , Neoplasias Mamárias Experimentais/terapia , Receptores de Superfície Celular/imunologia , Animais , Anticorpos Monoclonais/imunologia , Apoptose , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Colágeno/metabolismo , Neoplasias do Colo/imunologia , DNA/uso terapêutico , Combinação de Medicamentos , Sinergismo Farmacológico , Endoglina , Endotélio Vascular/citologia , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Laminina/metabolismo , Depleção Linfocítica , Neoplasias Mamárias Experimentais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Células NIH 3T3 , Neovascularização Patológica , Oligodesoxirribonucleotídeos , Proteoglicanas/metabolismo , Telangiectasia Hemorrágica Hereditária , Veias Umbilicais/citologia , Veias Umbilicais/imunologia , Veias Umbilicais/metabolismo
9.
Gan To Kagaku Ryoho ; 34(12): 1961-3, 2007 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-18219865

RESUMO

The authors analyzed the 25-patient who underwent a removal of W-spiral (WS) catheter after cessation of hepatic arterial infusion (HAI) chemotherapy. The catheter was easily removed in all cases, which resulted in improved patients' quality of life as well as preserved patency of hepatic arteries. However, arterial bleeding was occurred postoperatively in one case, which needed a surgical treatment. Although HAI using WS catheter and subsequent removal of the catheter is a reasonable strategy, a careful management of some complications should be considered.


Assuntos
Cateterismo/métodos , Hepatectomia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Cateterismo/efeitos adversos , Feminino , Hemorragia/cirurgia , Artéria Hepática/patologia , Artéria Hepática/cirurgia , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Tomógrafos Computadorizados
10.
Gan To Kagaku Ryoho ; 34(12): 2041-3, 2007 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-18219892

RESUMO

Multiple regional metastases due to colon cancer usually show poor prognosis. Various treatments such as chemotherapy and radiation therapy are not sufficient, and the outcome is generally poor in many cases. We report here on a patient with multiple regional metastases who was successfully treated with several therapies and remains still alive. A 69-year-old man presented with fever and epigastralgia. A colonoscopy revealed primary sigmoid colon cancer. A computed tomography showed multiple hepatic metastases, and metastases to supraclavicular, mediastinal and para-aortic regional lymph nodes. The bone metastases were detected by scintigram. He was treated with combination chemotherapy of 5-FU via hepatic artery and CPT-11 by systemic administration. The primary tumor had completely disappeared (complete response), and metastases to liver and lymph nodes showed a remarkable shrinkage (partial response) after the chemotherapy. In contrast, bone metastases showed progressive growth (progressive disease). Radiation therapy and bisphosphonate infusion for bone metastases were achieved, and the treatments have controlled the growth of the metastases. Primary tumors and metastases are still controlled well for 3 years after the initial chemotherapy.


Assuntos
Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/radioterapia , Idoso , Colonoscopia , Humanos , Masculino , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Metástase Neoplásica/radioterapia , Neoplasias do Colo Sigmoide/classificação , Neoplasias do Colo Sigmoide/patologia , Tomografia Computadorizada por Raios X
11.
Gan To Kagaku Ryoho ; 34(8): 1299-302, 2007 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-17687218

RESUMO

A 68-year-old woman was on dialysis for the treatment of chronic renal failure. FOLFOX 4 therapy was performed following CPT-11+UFT+Leucovorin for liver metastasis after resection of cancer of the sigmoid colon. The dose of oxaliplatin was 40 mg/m2, while 5-FU was given as a bolus of 300 mg/m2, and a continuous intravenous infusion of 500 mg/m2. Hemodialysis was performed 1 hour after administration of oxaliplatin on day 1 and was repeated two days later after the completion of drug administration. Vomiting (grade 2),anorexia and leukopenia (both grade 3) were observed after the first treatment. A total of 4 courses were administered thereafter by reducing the dose of oxaliplatin to 32 mg/m2, the intravenous bolus of 5-FU to 240 mg/m2, and continuous infusion of 5-FU to 400 mg/m2. Measurement of drug concentrations showed that free platinum was immediately eliminated by dialysis. It was considered possible to safely perform FOLFOX 4 therapy in patients with chronic renal failure by reducing the doses and by providing dialysis. It is desirable to measure drug concentrations in these patients. Also,more cases should be monitored to investigate the safe dose,the blood drug concentration profile, and the accumulation of chemotherapy agents.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Falência Renal Crônica/terapia , Diálise Renal , Neoplasias do Colo Sigmoide/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Vias de Administração de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Humanos , Falência Renal Crônica/complicações , Leucovorina/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/sangue , Oxaliplatina , Platina/sangue , Neoplasias do Colo Sigmoide/sangue , Neoplasias do Colo Sigmoide/complicações
12.
Chemosphere ; 62(3): 469-84, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15946725

RESUMO

Special polychlorinated biphenyls (PCBs) standards (native and isotope labeled) were analyzed by isotope dilution method using HRGC-HRMS. Multiple analysis of special PCBs standards by three different laboratories produced the relative response factors (RRFs) and relative standard deviations (RSDs %) was in the average of 0.979 and 3.86, respectively. Additionally, inter-laboratory analysis of various forms of transformer oil revealed the PCBs concentrations were in the following order; PCBs fortified transformer oil (940-1300 ng/g)>PCB polluted transformer oil (490-680 ng/g)>chemically degraded-transformer oil (480-490 ng/g) and PCBs free oil (ND-17 ng/g). Chemical degradation resulted in an order of magnitude decrease in the PCB concentrations. Specifically, higher chlorinated PCBs degraded into lower chlorinated PCBs. Also, composition of PCBs have been determined in PCB formulations from Japan (Kanechlor), Germany (Clophen), USA (Aroclor), Russia (Sovol) and Poland (Chlorofen). Major PCBs (24-PCB congeners) contributed 54-67%, 55-68%, 16-69%, 71% and 72% in Kanechlor, Clophen, Aroclor, Sovol and Chlorofen, respectively to total PCBs. The homologue pattern of Kanechlor, Aroclor and Clophen in technical fromulation was similar (e.g., Kanechlor-300 resembled to those of Clophen A-30 and Aroclor-1242). Furthermore, congener-specific distributions of major PCBs/dioxin-like PCBs and toxic equivalency quantities (TEQ) were calculated. Based on our tentative assumption calculations, cumulative production of five different technical PCB formulations, WHO-TEQ emission was estimated to be approximately 16.05 tons.


Assuntos
Poluentes Ambientais/análise , Óleos Industriais/análise , Bifenilos Policlorados/análise , Calibragem , Isótopos de Carbono , Cromatografia Gasosa-Espectrometria de Massas , Óleos Industriais/normas
13.
Gan To Kagaku Ryoho ; 33(12): 1756-8, 2006 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-17212098

RESUMO

In order to establish a reasonable prophylactic hepatic arterial infusion (HAI) chemotherapy following curative resection of colorectal liver metastases, the authors performed a randomized control study comparing two regimen. A weekly 5 hour-administration of 5-FU (1500 mg) which was repeated for 8 weeks showed a comparable effect to a continuous infusion group with an identical total dosage of 5-FU. Furthermore, adverse events were observed in only several patients of each group with low grade severity, suggesting that this simple regimen with a weekly HAI is promising. We also analyzed the clinical course of patients receiving HAI using a W spiral catheter which has a shape memory alloy in its tip. The catheter was implanted angiographycally without coil fixation to the vascular wall, which allowed us to remove the catheter after cessation of the scheduled chemotherapy. In all of the patients, the catheters were easily removed without any complications. A 3D-CT angiograph revealed that the hepatic arteries were well patent in all of the patients with a 3.3 Fr type catheter. HAI chemotherapy is basically an invasive treatment. In consideration of its efficacies as well as limitations, a reasonable approach is needed from the viewpoint of patients' quality of life.


Assuntos
Neoplasias Colorretais/patologia , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/secundário , Angiografia , Cateterismo , Fluoruracila/efeitos adversos , Artéria Hepática/diagnóstico por imagem , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Qualidade de Vida , Estudos Retrospectivos
14.
Gan To Kagaku Ryoho ; 33(12): 1953-5, 2006 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-17212157

RESUMO

Sigmoidectomy was performed for a 69-year-old man with sigmoid colon cancer and unresectable multiple liver metastases. The histological diagnosis was undifferentiated carcinoma of sigmoid colon. Hepatic arterial infusion chemotherapy with 5 FU and systemic chemotherapy with CPT-11 were performed after the operation. A complete response (CR) was achieved for liver metastases. The recurrent sign was not found at 23 months after the operation. This combination therapy is expected to be an alternative treatment of colorectal cancer with unresectable multiple liver metastases.


Assuntos
Camptotecina/análogos & derivados , Carcinoma/patologia , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias do Colo Sigmoide/patologia , Idoso , Camptotecina/administração & dosagem , Carcinoma/cirurgia , Colectomia , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Irinotecano , Masculino , Indução de Remissão , Neoplasias do Colo Sigmoide/cirurgia
15.
Environ Sci Pollut Res Int ; 9(5): 337-44, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12391810

RESUMO

Control of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in emissions and thermal residues from incinerators has been a cause of public concern for more than one decade. Recently, several studies showed that other persistent organic pollutants (POPs) such as coplanar polychlorinated biphenyls (co-PCBs) also have dioxin-like activity and are released from incinerators. Therefore, the present study was aimed at making a risk assessment about dioxin-like activity in extracts of thermal waste residues (e.g. combustion gas; fly ash, slag) from incineration and melting processes in Germany and Japan. For this purpose, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), coplanar polychlorinated biphenyls (co-PCBs), polychlorinated naphthalenes (PCNs) and polyaromatic hydrocarbons (PAHs) were analyzed by chemical analysis. Additionally, 2, 3, 7, 8-TCDD equivalents (EROD-TEQs) were determined by in vitro Micro-EROD bioassay using rat H4IIE hepatoma cells. EROD-TEQs could be correlated to I-TEQ values (from PCDD/Fs/co-PCBs) analyzed by chemical analysis resulting in a maximal sixfold higher estimate. Our study indicates minor influences of co-PCBs, PAHs and PCNs to the sum of dioxin-like toxicity in the extracts of thermal waste residues as determined here. Furthermore, we showed that the levels of dioxins and co-PCBs contained in slag from melting processes and bottom ashes from incineration processes were lower by 1-2 orders of magnitude than that in fly ash.


Assuntos
Poluentes Atmosféricos/análise , Poluentes Ambientais/análise , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Eliminação de Resíduos , Poluentes do Solo/análise , Bioensaio , Citocromo P-450 CYP1A1/análise , Citocromo P-450 CYP1A1/biossíntese , Poluentes Ambientais/efeitos adversos , Incineração , Bifenilos Policlorados/efeitos adversos , Dibenzodioxinas Policloradas/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Medição de Risco , Poluentes do Solo/efeitos adversos , Temperatura
16.
Ann Diagn Pathol ; 11(3): 212-6, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17498596

RESUMO

The diagnosis of gastrointestinal stromal tumor (GIST) is generally established on histopathologic examination of surgical specimens. Gastrointestinal stromal tumor comprises a heterogenous group of neoplasms of the gastrointestinal tract previously referred to as leiomyomas, leiomyosarcomas, or schwannomas. Gastrointestinal stromal tumor arising from anorectum is a rare instance. We report a case of GIST for the correlation of imaging and cytologic features with immunocytochemical staining. A computed tomography and magnetic resonance imaging confirmed a 2-cm tumor growing into the rectal lumen. The central portion of the tumor showed T1-weighted imaging of low signal and suspected central necrosis by the T2-weighted imaging of high signal. Imprint cytology from excised tumors showed isolated or loosely aggregated spindle cells with scanty and fibrillary cytoplasmic processes, nuclear pleomorphism, fine granular chromatin, and irregular nuclear margins. Epithelioid tumor cells showed grooves with abundant cytoplasm and several round nucleoli. Both c-kit and CD34 antigen were positive with strong and diffuse stainability in smears as well as paraffin sections by immunoperoxidase staining. We suggest that the combined use of imaging diagnosis and cytology with immunocytochemical staining are useful initial diagnosis of GIST.


Assuntos
Canal Anal/patologia , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Reto/patologia , Idoso , Canal Anal/metabolismo , Antígenos CD34/genética , Antígenos CD34/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Neoplasias Gastrointestinais/metabolismo , Tumores do Estroma Gastrointestinal/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Reto/metabolismo , Tomografia Computadorizada por Raios X
17.
Cancer Immunol Immunother ; 55(2): 140-50, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15856228

RESUMO

We generated a human/mouse chimeric antibody c-SN6j of human IgG1 isotype from a murine anti-human endoglin (EDG) monoclonal antibody (mAb) SN6j that suppressed angiogenesis, tumor growth and metastasis in mice. We determined pharmacokinetics (PKs) and immunogenicity of c-SN6j in monkeys after multiple i.v. injections. A dose-escalation study was performed by administration of c-SN6j into six monkeys at the dose of 1 mg, 3 mg and 10 mg per kg body weight. In addition, both c-SN6j (3 mg/kg) and doxorubicin (0.275 mg/kg) were injected into two monkeys. c-SN6j and doxorubicin were injected twice a week for 3 weeks. We developed a unique and sensitive ELISA by sequentially targeting the common and idiotypic epitopes of c-SN6j-Fv to quantify plasma c-SN6j. Application of the ELISA showed that increasing the c-SN6j dose resulted in a proportional increase in the circulating c-SN6j after the first injection. In addition, the estimated area under the curve (AUC) for the first injection of c-SN6j is proportional to dose. We carried out detailed analyses of PKs of c-SN6j during and after the repeated injections. Our model of PKs fitted the empirical data well. Addition of doxorubicin modulated the PK parameters. We developed two ELISAs to separately determine the immune responses to the murine part and the human part of c-SN6j in monkeys. Interestingly, the murine part induced a weaker immune response than the human part. Doxorubicin potentiated the immune responses. Increasing the dose of c-SN6j increased plasma levels of c-SN6j but did not increase the immune responses to c-SN6j.


Assuntos
Inibidores da Angiogênese/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacocinética , Doxorrubicina/farmacologia , Proteínas Recombinantes de Fusão/imunologia , Molécula 1 de Adesão de Célula Vascular/imunologia , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacocinética , Animais , Anticorpos Monoclonais/administração & dosagem , Antígenos CD , Relação Dose-Resposta Imunológica , Doxorrubicina/administração & dosagem , Doxorrubicina/imunologia , Avaliação Pré-Clínica de Medicamentos , Endoglina , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Injeções Intravenosas , Macaca fascicularis , Modelos Animais , Receptores de Superfície Celular , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/farmacocinética , Distribuição Tecidual
18.
Environ Sci Technol ; 36(23): 5211-7, 2002 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-12523440

RESUMO

To investigate the dechlorination of fly ash during low-temperature treatment under oxygen-deficient conditions (thermocatalyic treatment or Hagenmaier process), six fly ash samples from six different incineration plants were treated in a laboratory experiment or in the actual plant, either under ideal (400 degrees C, 120 min) or intermediate (300 degrees C, 30 min) conditions. The aim of the present study was to confirm the decrease in the I-TEQ (international toxicity equivalency) of polychlorinated dibenzo-p-dioxins/-furans (PCDD/Fs) and coplanar polychlorinated biphenyls (co-PXBs) and, also for the first time, the decrease in the sum of dioxin-like toxicity (bioassay- or bio-TEQ) of all kinds of other dioxin-like Ah receptor agonists (such as PXDD/Fs, PXBs, PXN, X = Br, F) measured by two state-of-the-art cell-based Ah receptor-dependent bioassays: H4IIE-Ethoxy-Resorufin-o-Deethylase (EROD) and H4IIE-luc/DR-Chemical Activated Luciferase expression (DR-CALUX). The treatment efficiency was calculated on the basis of the reduction in the I-TEQ and bio-TED values. For these fly ash samples, the treatment efficiency, as measured by chemical analysis, was higher than 99%, and 85%-99%, in the case of the bio-TED values, indicating that these Ah receptor binding toxic compounds were sufficiently decomposed. Bio-TEQ values for untreated fly ash samples (n = 6) were on average 1.2 times (range 0.7-1.9), for the H4IIE-EROD assay, and 2.8 times (1.1-4.9), for the DR-CALUX assay, higher than I-TEQ values measured by chemical analyses (sum of PCDD/Fs and co-PCBs). In the case of these fly ash samples treated under ideal conditions and therefore low in contaminants, the bio-TEQ values were on average 1.4 times (range 0.9-1.8), for the H4IIE-EROD assay, and 5.1 times (range 1.2-12), for the DR-CALUX assay, higher than the I-TEQ values.


Assuntos
Dioxinas/efeitos adversos , Dioxinas/química , Poluentes Ambientais/efeitos adversos , Bioensaio , Catálise , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP1A1/farmacologia , Incineração , Luciferases/biossíntese , Luciferases/farmacologia , Oxigênio , Eliminação de Resíduos , Temperatura
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