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1.
Tumori ; 107(3): 231-237, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32878562

RESUMO

PURPOSE: Lung adenocarcinoma is histologically diverse but has distinct histologic growth patterns. There is no consensus on the clinical benefit of this histologic model. We aimed to evaluate the differences in the distribution of the preoperative primary tumor positron emission tomography (PET)/computed tomography (CT) standardized uptake values (SUVs) and survival in the lung adenocarcinoma subtypes. METHODS: We retrospectively evaluated the data of 107 patients with resected lung adenocarcinoma who had preoperative PET/CT between 2005 and 2017 in a single center. Patients had lepidic, acinar, papillary, micropapillary, and solid histologic subtypes. We compared fluorodeoxyglucose SUVs and survival data of histologic subtypes. RESULTS: The median age of the patients was 62 years (40-75), 76.4% were male, the median SUVmax was 9.4 (1-36.7), and the median follow-up time was 29 months (3-135 months). The median overall survival (OS) was 71 months and the median progression-free survival (PFS) was 33 months. SUVmax was significantly different in histologic subtypes: values for papillary, micropapillary, solid, acinar, and lepidic subtypes were 9.7, 8, 12, 9.1, and 3.9, respectively (p = 0.000). Solid predominant adenocarcinoma had significantly higher SUVmax than the other subtypes (p = 0.001). Lepidic predominant adenocarcinoma had significantly lower SUVmax than the other subtypes (p = 0.000). There was no significant difference in OS between histologic subtypes (p = 0.66), but PFS was significantly different between the groups (p = 0.017), and the solid subtype had a shorter PFS than the other histologic subtypes. CONCLUSION: Lung adenocarcinoma consists of a diverse group of diseases. Different SUVmax values are seen in different histologic subtypes of nonmetastatic lung adenocarcinoma. Solid predominant types have high SUVmax values while lepidic predominant types have lower SUVmax values. The solid subtype had a shorter PFS than the other histologic subtypes.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Adulto , Idoso , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos
2.
Aust Dent J ; 63(2): 261-264, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29281754

RESUMO

Peri-implant squamous cell carcinoma is an uncommon pathological manifestation, whereas peri-implantitis is commonly found in association with dental implants. Both present similarly with loss of supporting soft and hard tissue around dental implants; therefore, a careful differential diagnosis is required. The present case concerns a 62-year-old Japanese man who had a dental implant which had been in the left maxillary incisor region for 4 years who apparently developed peri-implantitis. This did not respond to localized therapy and antibiotics so was referred for specialist surgical management. A biopsy confirmed it to be a squamous cell carcinoma rather than an inflammatory lesion. A literature review shows that this is an unusual presentation without a previous history of malignancy, mucosal disease or risk factors for cancers. Although rare, the possibility of peri-implant squamous cell carcinoma should be borne in mind by all practitioners who monitor implant patients.


Assuntos
Carcinoma de Células Escamosas/etiologia , Implantes Dentários/efeitos adversos , Neoplasias Bucais/etiologia , Peri-Implantite/diagnóstico , Biópsia , Humanos , Inflamação , Japão , Masculino , Pessoa de Meia-Idade , Fatores de Risco
3.
Int J Oral Maxillofac Surg ; 44(5): 664-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25496849

RESUMO

The aim of this study was to investigate the capacity of human dental follicle cells (hDFCs) for bone formation in vivo. hDFCs were obtained from wisdom teeth extracted from patients aged 14 and 22 years. hDFCs from the 5th to 8th passages were grown in three-dimensional (3D) culture using gelatin sponges. Cells were transplanted onto the calvaria of F344/NJcl-rnu/rnu male rats (immunodeficient rats). Haematoxylin and eosin (HE) staining and immunohistochemistry were performed, and newly formed bone was evaluated by micro-computed tomography (micro-CT). HE staining showed newly formed bone in 3D culture. Immunohistochemistry showed bone morphogenetic protein 2 (BMP-2), runt-related transcription factor 2 (RUNX2), and osterix staining in areas with newly formed bone. Furthermore, micro-CT showed that, in comparison to controls, transplanted hDFCs promoted better bone quality and bone mineral density (BMD 582 ± 131.1 vs. 300.5 ± 77.7 mg/cm(3); P=0.039), bone mineral content (BMC 5.6 ± 1.1 vs. 2.1 ± 0.4 mg; P = 0.006), bone volume (BV 9.7 ± 0.5 × 10(-3) vs. 7.0 ± 0.4 × 10(-3) cm(3); P = 0.002), BMC/total volume (TV) (399.9 ± 76.3 vs. 147.7 ± 30.8 mg/cm(3); P = 0.006), and BV/TV (69.1 ± 3.6% vs. 49.6 ± 3.1%; P=0.002). This suggests that human dental follicles are potentially useful for regenerative therapy.


Assuntos
Regeneração Óssea/fisiologia , Saco Dentário/citologia , Adolescente , Animais , Proteína Morfogenética Óssea 2/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Projetos Piloto , Ratos , Ratos Endogâmicos F344 , Microtomografia por Raio-X , Adulto Jovem
4.
Transl Psychiatry ; 3: e252, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23632456

RESUMO

Ligands for ErbB receptors, including epidermal growth factor (EGF) and neuregulin-1, have a neurotrophic activity on midbrain dopaminergic neurons and are implicated in the pathophysiology of schizophrenia. Although ErbB kinase inhibitors ameliorate behavioral deficits of the schizophrenia model that was established by hippocampal lesioning of rat pups, the antipsychotic action of ErbB kinase inhibitors and its general applicability to other models are not fully characterized. Using a different animal model, here, we examined whether and how ErbB kinase inhibitors ameliorate the behavioral endophenotypes relevant to schizophrenia. The animal model for schizophrenia was prepared by exposing neonatal rats to the cytokine EGF. Intraventricular infusion of the ErbB1 inhibitors ZD1839 and PD153035 in these animals ameliorated the deficits in startle response and prepulse inhibition in a dose-dependent manner. The deficits of latent inhibition of fear learning were also alleviated by ZD1839 with its limited effects on body weight gain or locomotor activity. ZD1839 infusion also decreased the busting activity of nigral dopamine (DA) neurons and reduced pallidal DA metabolism, a result that mimics the anti-dopaminergic profile of risperidone and haloperidol in this brain region. ErbB inhibitors appear to have anti-dopaminergic actions to alleviate some of the behavioral deficits common to animal models for schizophrenia.


Assuntos
Antipsicóticos/uso terapêutico , Neurônios Dopaminérgicos/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Quinazolinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Animais , Química Encefálica/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fator de Crescimento Epidérmico/análise , Fator de Crescimento Epidérmico/farmacologia , Feminino , Gefitinibe , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reflexo de Sobressalto/efeitos dos fármacos , Psicologia do Esquizofrênico
5.
Xenotransplantation ; 17(4): 288-99, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20723201

RESUMO

BACKGROUND: Baboons are commonly used as models for transplantation and preclinical testing of various types of therapeutic agents. For proper assessment of information gathered from these models, differences between the baboon and human immune systems need to be characterized. Natural killer (NK) cells are the first line of defense against many infectious agents and cancer and are important mediators of transplantation rejection reactions, particularly during xenotransplantation. In this study, we examined baboon NK cell function and developed methods for purifying and expanding these cells. METHODS: Baboon NK cells were analyzed using a combination of extracellular and intracellular cell staining, cell sorting, interleukin (IL)-2 mediated stimulation and expansion, and 4 h cytotoxicity assays with human and pig target cell lines. RESULTS: Baboon peripheral blood mononuclear cell (PBMC) exert very low but detectable cytolytic activity against both human (K562) and pig (PAEC, J2) target cells, and this activity is enhanced within 4 h of treatment with IL-2. Like human NK cells, many baboon PBMC express the lytic enzymes granzyme A, granzyme B, and perforin. Based on these markers, we identified a subpopulation of CD3(-) baboon lymphocytes that are CD8(dim) and CD16(bright) that likely represents the baboon NK cells. These cells also are characterized by expression of the natural cytotoxicity receptor NKp46. Baboon CD3(-)NKp46(+) cells purified by flow cytometric cell sorting have high cytolytic capacity that can be further enhanced by IL-2 stimulation. These baboon NK cells can be expanded in vitro and retain extremely high cytolytic capacity. While fresh baboon lymphocytes express very little CD56, the expanded baboon NK cells are predominantly CD56(+); approximately 10% of the expanded NK cells are CD56(dim), and the remainder are CD56(bright). CONCLUSIONS: Baboon NK cells that are IL-2 responsive can be identified on the basis of a CD3(-)NKp46(+)CD8(dim)CD16(+/-) or CD3(-)CD8(dim)CD16(bright) phenotype and can be isolated and expanded in culture. These results may allow for a more accurate representation of the human innate immune system in baboon models and more accurate analyses of the role of the baboon innate immune system cells in preclinical models.


Assuntos
Citotoxicidade Imunológica/imunologia , Células Matadoras Naturais/imunologia , Papio/imunologia , Animais , Antígenos CD/imunologia , Linhagem Celular , Humanos , Interleucina-2/imunologia , Células Matadoras Naturais/citologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia
6.
Int Immunol ; 20(11): 1427-37, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18820264

RESUMO

During T cell activation, TCRs cluster at the center of the T cell-antigen-presenting cell interface forming the central supramolecular activation cluster. Although it has been suggested that sphingolipid- and cholesterol-rich microdomains, termed lipid rafts, form platforms for the regulation and transduction of TCR signals, an actual role for membrane sphingomyelin (SM), a key component of lipid rafts, has not been reported. After cloning a gene responsible for SM synthesis, sphingomyelin synthase (SMS) 1, we established a SM-knockdown cell line (Jurkat-SMS1/kd) by transfection of SMS1-short-interfering RNA into Jurkat T cells, which is deficient in membrane expression of SM. Upon CD3 stimulation, expression of CD69 (the earliest leukocyte activation antigen), activation-induced cell adhesion and proliferation as well as TCR clustering was severely impaired in Jurkat-SMS1/kd cells. CD3-induced tyrosine phosphorylation and association of linker for activation of T cell with ZAP-70 and Grb2 and phosphorylation of protein kinase C (PKC) were also severely impaired in Jurkat-SMS1/kd cells. Finally, translocation of TCR, ZAP-70 and PKC into lipid rafts was markedly decreased in Jurkat-SMS1/kd cells. These findings indicate that membrane SM is crucial for TCR signal transduction, leading to full T cell activation through lipid raft function.


Assuntos
Microdomínios da Membrana/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptor Cross-Talk/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo , Antígenos CD/biossíntese , Antígenos CD/genética , Antígenos de Diferenciação de Linfócitos T/biossíntese , Antígenos de Diferenciação de Linfócitos T/genética , Complexo CD3/metabolismo , Adesão Celular/genética , Fracionamento Celular , Ensaios de Migração Celular , Proliferação de Células , Cromatografia Líquida de Alta Pressão , Técnicas de Silenciamento de Genes , Humanos , Células Jurkat , Lectinas Tipo C , Ativação Linfocitária/genética , Microdomínios da Membrana/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Fosforilação , RNA Interferente Pequeno/genética , Agregação de Receptores/genética , Linfócitos T/citologia , Linfócitos T/imunologia , Transferases (Outros Grupos de Fosfato Substituídos)/genética
7.
Rev. psicol. polit ; 7(14): 0-0, dez. 2007.
Artigo em Português | LILACS | ID: lil-504470

RESUMO

O artigo propõe uma reflexão, a partir da psicologia social, sobre a relação entre ideologia e crítica nas políticas públicas, focalizando algumas interfaces da psicologia social com a ciência política, a lógica, a antropologia e a sociologia e implicando a discussão do objeto da psicologia social como sendo de caráter interdisciplinar, assim como seu método. Tal método apóia-se também na relação entre hermenêutica e filologia, na elucidação de premissas que sustentam a argumentação lógica, base da racionalidade e, portanto, da crítica.


The article proposes a reflection, based on social psychology, about the relation between ideology and criticism in public policies, focusing on some interfaces of social psychology with politics, logic, anthropology and sociology, and implying the discussion of the object of social psychology as being of an interdisciplinary nature, as well as its method. This method is also supported by the relation between hermeneutics and philology, by the elucidation of premises that sustain the logical argumentation - the basis of rationality and, therefore, of criticism.


Assuntos
Política Pública , Psicologia Social
8.
Rev. psicol. polít ; 7(14)dez. 2007.
Artigo em Português | Index Psicologia - Periódicos | ID: psi-47482

RESUMO

O artigo propõe uma reflexão, a partir da psicologia social, sobre a relação entre ideologia e crítica nas políticas públicas, focalizando algumas interfaces da psicologia social com a ciência política, a lógica, a antropologia e a sociologia e implicando a discussão do objeto da psicologia social como sendo de caráter interdisciplinar, assim como seu método. Tal método apóia-se também na relação entre hermenêutica e filologia, na elucidação de premissas que sustentam a argumentação lógica, base da racionalidade e, portanto, da crítica.(AU)


The article proposes a reflection, based on social psychology, about the relation between ideology and criticism in public policies, focusing on some interfaces of social psychology with politics, logic, anthropology and sociology, and implying the discussion of the object of social psychology as being of an interdisciplinary nature, as well as its method. This method is also supported by the relation between hermeneutics and philology, by the elucidation of premises that sustain the logical argumentation - the basis of rationality and, therefore, of criticism.(AU)


Assuntos
Política Pública , Psicologia Social
9.
Xenotransplantation ; 14(4): 298-308, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17669171

RESUMO

BACKGROUND: It is well established that CD4(+)CD25(+) regulatory T (Treg) cells can modulate allogeneic immune responses. Xenotransplantation, proposed as a means to address the critical shortage of human organs, may also benefit from similar approaches to avert rejection. Baboons are a preferred preclinical animal model for xenogeneic organ transplantation experiments, and the characterization of baboon Treg cells will be beneficial to future tolerance studies in this animal model. METHODS: We analyzed CD4(+)CD25(+) T cells from baboon lymph nodes, spleens, and blood by flow cytometry, then purified and expanded porcine antigen-specific baboon CD4(+)CD25(high) cells in vitro to evaluate their regulatory activity in the baboon anti-pig xenogeneic responses. RESULTS: CD4(+)CD25(high) T cells were 1.7%, 3.1%, and 1.9% of baboon splenic, lymph node, and blood T cells, respectively. The CD4(+)CD25(high) T cells expressed the Treg cell-associated transcription factor, FoxP3. Proliferation/suppression assays using irradiated pig peripheral blood mononuclear cells as stimulators showed that Treg cells suppressed the vigorous baboon CD4(+)CD25(-) T-cell anti-pig proliferation response and cytokine secretion. Expanded baboon Treg cells suppressed baboon anti-pig CD4(+)CD25(-) T-cell proliferation approximately 4- to 10-fold more than freshly isolated Treg cells. Expanded Treg cells suppressed proliferation to primary cells from the same pig used for expansion more effectively than proliferation to stimulators from a different strain of pig, suggesting a level of antigen specificity. CONCLUSION: We demonstrate that baboon Treg cells suppress immune responses to xenogeneic stimulation. These studies suggest that adoptive transfer of expanded Treg cells into transplant recipients may provide an approach to prevent cell-mediated rejection of grafts and potentially induce tolerance in the pig to baboon xenotransplantation preclinical model.


Assuntos
Tolerância Imunológica/imunologia , Papio/imunologia , Linfócitos T Reguladores/imunologia , Transplante Heterólogo/imunologia , Animais , Antígenos CD4 , Células Cultivadas , Humanos , Subunidade alfa de Receptor de Interleucina-2 , Teste de Cultura Mista de Linfócitos , Suínos/sangue , Suínos/imunologia , Linfócitos T Reguladores/transplante
10.
Xenotransplantation ; 14(4): 345-6, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17669177

RESUMO

An overview of xenotransplantation regulatory policies in the USA was presented at the Satellite Symposium, ''Xenotransplantation--Current Standards for Clinical Trials,'' held in conjunction with the World Transplant Congress, Boston, MA, USA 2006. This article summarizes that overview.


Assuntos
Guias como Assunto , Transplante Heterólogo/legislação & jurisprudência , Transplante Heterólogo/normas , United States Food and Drug Administration , Animais , Ensaios Clínicos como Assunto/normas , Humanos , Política Pública , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , United States Food and Drug Administration/normas
11.
Antioxid Redox Signal ; 9(6): 751-6, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17511591

RESUMO

Pluripotent human embryonic stem cells (hESCs) may provide a potential source of cellular therapies, but as allogeneic cells may require evading the recipient's immune response. Using an NIH-registry hESC line, it was found that undifferentiated hESCs induce a reduced proliferative response compared to PBMC and demonstrate that this diminished response correlates with the activity of heme oxygenase-1 (HO-1). Inhibition of HO-1 significantly increases T cell proliferation against hESC, indicating the potential suppression of these cells during transplantation of allogeneic hESC. These data suggest the hypothesis that HO-1 provides a mechanism for protecting hESCs in vivo.


Assuntos
Células-Tronco Embrionárias/enzimologia , Células-Tronco Embrionárias/imunologia , Heme Oxigenase-1/imunologia , Heme Oxigenase-1/metabolismo , Proliferação de Células , Células Cultivadas , Proteínas de Choque Térmico/metabolismo , Heme Oxigenase-1/antagonistas & inibidores , Humanos , Linfócitos/citologia , Linfócitos/enzimologia , Linfócitos/imunologia
12.
Int Immunol ; 19(2): 163-73, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17182966

RESUMO

NK cells, a component of the innate immune system, provide a first line of defense against viral infections and malignancies, interact with the adaptive immune system and have a role in rejection of allogeneic bone marrow transplants and solid allo- and xenotransplants. Immunoregulatory activity by the anti-hypercholesterolemia agents, 3-hydroxy-3-methyl-glutaryl Coenzyme A (HMG-CoA) reductase inhibitors, known as statins, has recently been reported. We analyzed the effects of three statins on human NK cell cytotoxicity. Two lipophilic statins (simvastatin and fluvastatin) suppressed the cytotoxic activity of fresh and IL-2-stimulated NK cells, while pravastatin, a hydrophilic statin, did not. Suppression was not associated with changes in intracellular perforin, granzyme A or granzyme B levels, or with changes in expression of leukocyte function-associated antigen-1, an integrin known to regulate NK activity and reported to be altered by statin treatment. Decreased cytotoxicity was associated with decreased CD107a surface expression, indicating that the exocytosis pathway was compromised by simvastatin and fluvastatin but not by pravastatin. Mevalonate, the immediate downstream product of HMG-CoA reductase, partially reversed the effect of lipophilic statins on cytotoxicity and CD107a expression. Lipophilic statins also suppressed the release of the granule component, granzyme B, by IL-2-activated NK cells following stimulation with K562. That lipophilic statins suppress NK cell activity through inhibition of the exocytosis pathway suggest an additional potential role for statins in inhibition of transplantation responses.


Assuntos
Grânulos Citoplasmáticos/efeitos dos fármacos , Citotoxicidade Imunológica/efeitos dos fármacos , Exocitose/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Linhagem Celular , Grânulos Citoplasmáticos/metabolismo , Ensaio de Imunoadsorção Enzimática , Ácidos Graxos Monoinsaturados/farmacologia , Fluvastatina , Granzimas/efeitos dos fármacos , Granzimas/metabolismo , Humanos , Indóis/farmacologia , Células Matadoras Naturais/imunologia , Proteína 1 de Membrana Associada ao Lisossomo/biossíntese , Proteína 1 de Membrana Associada ao Lisossomo/efeitos dos fármacos , Ácido Mevalônico/metabolismo , Pravastatina/farmacologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sinvastatina/farmacologia
13.
Kyobu Geka ; 59(10): 913-5, 2006 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-16986687

RESUMO

Heartstring is a useful device. However, the device failure at the time of loading the seal into the delivery device is a troublesome issue. To avoid this problem, we invent a new method using 2 tourniquets made of 5 mm-wide woven Teflon tapes and plastic tubes. Using our method, the loading procedure became easier and more reliable.


Assuntos
Ponte de Artéria Coronária/instrumentação , Torniquetes , Anastomose Cirúrgica/instrumentação , Ponte de Artéria Coronária/métodos , Humanos
14.
Xenotransplantation ; 13(4): 318-27, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16768725

RESUMO

BACKGROUND: Xenotransplantation of pig organs may provide an approach to alleviate the severe shortage of human organs. Natural antibodies against Galalpha(1,3)-Gal (alphaGal) epitopes cause hyperacute rejection of pig organs in primates. However, evidence for the role of alphaGal in the natural killer (NK) cell-mediated xenoresponse has been contradictory. METHODS: We investigated the recognition of alphaGal by human NK cells using endo-beta-galactosidase C, an enzyme that cleaves alphaGal, and endothelial cells (EC) from alpha1,3-galactosyltransferase null pigs that do not synthesize alphaGal. Endo-beta-galactosidase C treatment variably reduced the susceptibility of porcine EC to lysis by fresh human NK cells. RESULTS: Removal of alphaGal from porcine EC using endo-beta-galactosidase C, produced variable results, i.e. cytotoxicity was decreased in half of the human NK cell donors tested. The two EC strains from alphaGal-/- pigs were marginally, and not significantly, less susceptible to lysis by naïve human NK cells compared with alphaGal-expressing cells obtained from animals from the same herd, but these differences were not statistically significant (P > 0.10). Treatment of porcine EC with recombinant human tumor necrosis factor (TNF)-alpha, which is known to activate porcine EC, enhanced the susceptibility of all target cells to lysis by fresh human NK cells. Surface expression of MHC or adhesion molecules on alphaGal-/- cells, compared with wild type cells, showed no consistent difference in either MHC or adhesion molecules CD106 (VCAM-1), CD31 (PECAM) or CD62E (E-selectin), either with or without TNF-alpha stimulation, that could explain the differential susceptibility to lysis. Strikingly, all alphaGal-/- and wild type EC exhibited similar susceptibility to human NK cells that had been cultured for 5 days with or without interleukin-2. CONCLUSIONS: These findings demonstrate that human NK cells can kill porcine targets in the absence of alphaGal, and donor variability plays a major role in whether alphaGal has a role in determining susceptibility of porcine EC to lysis. Moreover, susceptibility to lysis of alphaGal null EC is enhanced to the level of wild type EC by activation of either effector or target cells. Elimination of alphaGal alone from source pigs will be insufficient to circumvent the NK cell mediated destruction of porcine EC.


Assuntos
Dissacarídeos/imunologia , Células Endoteliais/imunologia , Glicosídeo Hidrolases/metabolismo , Células Matadoras Naturais/imunologia , Animais , Aorta/citologia , Moléculas de Adesão Celular/análise , Citotoxicidade Imunológica , Antígenos de Histocompatibilidade/análise , Humanos , Interleucina-2/metabolismo , Células Matadoras Naturais/metabolismo , Suínos/imunologia
15.
J Bone Joint Surg Am ; 88(3): 503-7, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16510814

RESUMO

BACKGROUND: Carticel is an autologous cultured chondrocyte product that has been approved by the United States Food and Drug Administration for the repair of symptomatic cartilaginous defects of the femoral condyle that are caused by acute or repetitive trauma in patients who have been previously managed with arthroscopy or other surgical procedures. The present report describes the adverse events following Carticel implantation as reported to the Food and Drug Administration from 1996 to 2003. METHODS: We reviewed adverse event reports that had been submitted to the Food and Drug Administration's MedWatch system for information on demographic characteristics, adverse events, and surgical revisions. Adverse events were categorized into sixteen non-mutually exclusive groups. Five categories were used to classify reoperations. Food and Drug Administration regulations require manufacturers to report adverse events; however, reporting by clinicians and others is voluntary. Therefore, adverse event reporting is likely to underestimate the number of event occurrences. Adverse events may be either causally or coincidentally related to the product. RESULTS: A total of 497 adverse events among 294 patients receiving Carticel were reported. The median interval from Carticel implantation to the diagnosis of an adverse event was 240 days (range, one to 2105 days). The median age of the patients was thirty-eight years, and 63% of the patients were male. Of the 270 events for which the anatomic site was noted, 258 (96%) involved the femoral condyles. More than one adverse event was reported for 135 patients (46%). The most commonly reported events were graft failure (seventy-three patients; 25%), delamination (sixty-five patients; 22%), and tissue hypertrophy (fifty-two patients; 18%). In addition, eighteen surgical site infections were reported, including eleven joint and seven soft-tissue infections. Surgical revision subsequent to Carticel implantation was mentioned in the records for 273 patients (93%). The reasons for the 389 revision procedures included graft-related problems (187 procedures; 48.1%), periarticular soft-tissue problems (ninety-seven procedures; 24.9%), and intra-articular problems (sixty-three procedures; 16.2%). Eight patients had a total knee replacement. Based on the manufacturer's reported distribution of 7500 Carticel lots between 1995 and 2002, 285 patients (3.8%) had an adverse event that was reported to the Food and Drug Administration. CONCLUSIONS: The most common adverse events reported in association with the Carticel technique involved graft failure, delamination, and tissue hypertrophy.


Assuntos
Fatores Biológicos/efeitos adversos , Doenças das Cartilagens/cirurgia , Condrócitos/transplante , Vigilância de Produtos Comercializados , United States Food and Drug Administration , Adulto , Células Cultivadas , Feminino , Fêmur/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Periósteo/transplante , Reoperação , Infecção da Ferida Cirúrgica/etiologia , Transplante Autólogo/efeitos adversos , Estados Unidos
17.
J Exp Med ; 202(2): 249-59, 2005 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-16009715

RESUMO

Engagement of the Fas receptor (CD95) initiates multiple signaling pathways that lead to apoptosis, such as the formation of death-inducing signaling complex (DISC), activation of caspase cascades, and the generation of the lipid messenger, ceramide. Sphingomyelin (SM) is a major component of lipid rafts, which are specialized structures that enhance the efficiency of membrane receptor signaling and are a main source of ceramide. However, the functions of SM in Fas-mediated apoptosis have yet to be clearly defined, as the responsible genes have not been identified. After cloning a gene responsible for SM synthesis, SMS1, we established SM synthase-defective WR19L cells transfected with the human Fas gene (WR/Fas-SM(-)), and cells that have been functionally restored by transfection with SMS1 (WR/Fas-SMS1). We show that expression of membrane SM enhances Fas-mediated apoptosis through increasing DISC formation, activation of caspases, efficient translocation of Fas into lipid rafts, and subsequent Fas clustering. Furthermore, WR/Fas-SMS1 cells, but not WR/Fas-SM(-) cells, showed a considerable increase in ceramide generation within lipid rafts upon Fas stimulation. These data suggest that a membrane SM is important for Fas clustering through aggregation of lipid rafts, leading to Fas-mediated apoptosis.


Assuntos
Apoptose/fisiologia , Ceramidas/metabolismo , Microdomínios da Membrana/metabolismo , Transdução de Sinais/fisiologia , Esfingomielinas/metabolismo , Receptor fas/metabolismo , Animais , Apoptose/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Deleção de Genes , Humanos , Camundongos , Transporte Proteico/genética , Transporte Proteico/fisiologia , Transdução de Sinais/genética , Transfecção , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo , Receptor fas/genética
18.
Am J Transplant ; 5(8): 2052-7, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15996259

RESUMO

Due to the shortage of human organs, xenotransplantation is being explored as an alternative to allotransplantation, but immune rejection remains a major hurdle to its implementation. We tested the ability of human CD4+CD25+ T cells (Treg cells) to suppress CD4+ T cell-mediated anti-porcine xenoresponses usingin vitroassays. Human Treg cells were hyporesponsive to porcine cell stimulation and suppressed the proliferative response of CD4+CD25- T cells in a dose-dependent manner, and comparison of the allo- and xenoresponses indicated that more Treg cells might be required to suppress the xenogeneic response than the allogeneic response. Stimulation of CD4+CD25- T cells with porcine cells resulted in secretion of IFN-gamma, TNF-alpha, IL-10, IL-6 and IL-2, and Treg cells suppressed the secretion of these cytokines, as well as the CD4+CD25- T-cell cytolytic response against porcine cells. These results suggest a potential role for Treg cells in promoting xenograft survival.


Assuntos
Antígenos Heterófilos/imunologia , Linfócitos T CD4-Positivos/imunologia , Citocinas/metabolismo , Suínos/imunologia , Linfócitos T/imunologia , Animais , Humanos , Tolerância Imunológica , Receptores de Interleucina-2/imunologia , Receptores de Interleucina-2/metabolismo , Subpopulações de Linfócitos T/metabolismo
19.
Free Radic Biol Med ; 38(9): 1231-42, 2005 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15808421

RESUMO

Oxidative stress mediates positive and negative effects on physiological processes. Recent reports show that H(2)O(2) induces phosphorylation and activation of endothelial nitric oxide synthase (eNOS) through an Akt-phosphorylation-dependent pathway. In this study, we assessed activation of eNOS and Akt by determining their phosphorylation status. Whereas moderate levels of H(2)O(2) (100 microM) activated the Akt/eNOS pathway, higher levels (500 microM) did not, suggesting differential effects by differing levels of oxidative stress. We then found that two pro-oxidants with activity on sulfhydryl groups, 1-chloro-2,4-dinitrobenzene (CDNB) and diethyl maleate (DEM), blocked the phosphorylation events induced by 100 microM H(2)O(2). GSH was not a target thiol in this system because buthionine sulfoximine did not inhibit this phosphorylation. However, down-regulation of cell membrane surface and intracellular free thiols was associated with the inhibition of phosphorylation, suggesting that oxidation of non-GSH thiols inhibits the H(2)O(2)-induced phosphorylation of eNOS and Akt. DTT reversed the inhibitory effects of CDNB and DEM on Akt phosphorylation and concomitantly restored cell surface thiol levels more efficiently than it restored intracellular thiols, suggesting a more prominent role for the former. Similarly, DEM and CDNB inhibited TNF-alpha-induced Akt and eNOS phosphorylation, suggesting that thiol modification is involved in eNOS inductive pathways. Our findings suggest that eNOS activation is exquisitely sensitive to regulation by redox and that cell surface thiols, other than glutathione, regulate signal transduction leading to phosphorylation of Akt and eNOS.


Assuntos
Óxido Nítrico Sintase/metabolismo , Transdução de Sinais , Animais , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Endotélio Vascular/metabolismo , Glutationa/metabolismo , Peróxido de Hidrogênio/farmacologia , Óxido Nítrico Sintase Tipo III , Oxirredução , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Compostos de Sulfidrila/metabolismo , Suínos , Fator de Necrose Tumoral alfa/farmacologia
20.
Kyobu Geka ; 57(12): 1110-2, 2004 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-15553026

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) infection after cardiac surgery has recently increased. We compared the anti-inflammatory effect of an electrolyzed strong acid solution and a warm saline solution in patients with open heart surgery. These solutions were used for mediastinal irrigation before closing the sternum. Group A patients were irrigated by a warm saline solution, and group B patients were irrigated by an electrolyzed strong acid solution, administration of this water is safe, feasible, and easy for the prevention of MRSA infection. Postoperative infection was significantly decreased in the group B as compared in the group A. An electrolyzed strong acid solution may be effective on postoperative infection, particularly MRSA infection following open heart surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Peróxido de Hidrogênio/uso terapêutico , Mediastinite/prevenção & controle , Resistência a Meticilina , Complicações Pós-Operatórias/prevenção & controle , Infecções Estafilocócicas , Staphylococcus aureus/efeitos dos fármacos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Irrigação Terapêutica/métodos
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