RESUMO
The expression of the CC chemokine receptor-7 (CCR7) by cancers, including melanoma, augments lymph node (LN) metastasis, but little is known about its role in lymphangiogenesis and anti-tumor immunity. We injected control B16 murine melanoma cells (pLNCX2-B16) and CCR7-overexpressing B16 cells (CCR7-B16) in murine footpads and compared resulting tumors at the protein and mRNA level using immunostaining, Affymetrix gene microarray and quantitative reverse-transcriptase PCR. Although control and CCR7-B16 primary tumors were of similar size, LN metastasis was dramatically enhanced in CCR7-B16 tumors. Microarray analysis of leukocyte-depleted pLNCX2-B16 and CCR7-B16 tumor cell suspensions showed that three major groups of genes linked to interferon (IFN)-γ signaling pathways (for example, STAT1, CXCR 9-11, CCL5 and CXCL10, major histocompatibility complex (MHC) I and MHC II) were downregulated in the CCR7-B16 tumor microenvironment, suggesting activation through CCR7 can downregulate pathways critical for host anti-tumor immunity. In addition, mRNA expression of the lymphatic marker podoplanin was upregulated in CCR7-B16 tumors by 3.35-fold versus control tumors. Anti-podoplanin monoclonal antibody staining revealed a three-fold increase in intratumoral CCL21-expressing lymphatic vessels, as well as a two-fold increase in the number of invading tumor cells per lymphatic vessel in CCR7-B16 versus control tumors. Enhanced anti-vascular endothelial growth factor C (VEGF-C) staining was present in CCR7-B16 versus control tumors, suggesting that VEGF-C may have a role in the CCR7-mediated lymphangiogenesis. In summary, CCR7-B16 tumors show a striking decrease in IFN-γ-mediated inflammatory gene expression in contrast to increased expression of VEGF-C, CCL21 and podoplanin by lymphatic vessels. Enhanced lymphangiogenesis may contribute to the dramatic increase in LN metastasis that is observed in the CCR7-expressing tumors.
RESUMO
While treatment for cancer in terms of chemotherapy and radiation therapy have evolved significantly since their inception, both of these cancer treatment modalities, especially if used in combination (e.g., as with head and neck cancers), have a very real potential to result in painful and debilitating adverse effects that clearly decrease quality of life and, potentially, increase mortality due to cancer. Herein, we discuss the prevalence and etiology of three broad categories of oral complications found during the treatment of cancer patients: mucositis, dysgeusia, and infectious disease. Lastly, we present therapeutic options that may be helpful in ameliorating these uncomfortable and, sometimes, life-threatening oral complications.
Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Doenças da Boca/etiologia , Antineoplásicos/efeitos adversos , Candidíase Bucal/etiologia , Disgeusia/etiologia , Infecções por Herpesviridae/etiologia , Humanos , Hospedeiro Imunocomprometido , Doenças da Boca/terapia , Infecções Oportunistas/etiologia , Lesões por Radiação/etiologia , Estomatite/etiologiaRESUMO
BACKGROUND: It is unknown whether microalbuminuria is associated with non-alcoholic fatty liver disease (NAFLD) among patients with prediabetes and type 2 diabetes mellitus (DM). This study investigated the association of NAFLD with microalbuminuria among patients with prediabetes and diabetes. METHODS: We evaluated 1361 subjects who had an abnormal oral glucose tolerance test (OGTT) on routine screening. All participants were divided into two groups, prediabetes and newly diagnosed type 2 DM, and the association of NAFLD with metabolic parameters on microalbuminuria was analysed. RESULTS: The patients with NAFLD had higher prevalence rates of microalbuminuria (6.3% vs 19%; P = 0.001 in prediabetes, 4.5% vs 32.6%; P < 0.001 in diabetes) and also had a greater albumin-to-creatinine ratio (14.6 +/- 52.0 microg/mg Cr vs 27.7 +/- 63.9 microg/mg Cr; P = 0.051 in prediabetes, 11.4 +/- 21.4 microg/mg Cr vs 44.7 +/- 76.4 microg/mg Cr; P < 0.001 in diabetes) than those without NAFLD. The logistic regression analysis showed that NAFLD was associated with increased rates of microalbuminuria (odds ratio 3.66; 95%confidence interval (CI) 1.31-10.20, P = 0.013 in prediabetes, odds ratio 5.47;95% CI 1.01-29.61, P = 0.048 in diabetes), independently of age, sex, body mass index, waist circumference, liver enzymes, lipid profiles, HbA1c, insulin resistance as estimated by homeostasis model assessment, hypertension,smoking status and the metabolic syndrome. CONCLUSIONS: The results of our study revealed a strong relationship between microalbuminuria and NAFLD in the patients with prediabetes and newly diagnosed diabetes. Further studies are required to confirm whether NAFLD is a predictor of the development of microalbuminuria in patients with prediabetes and diabetes.
Assuntos
Albuminúria/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Fígado Gorduroso/epidemiologia , Estado Pré-Diabético/epidemiologia , Adulto , Albuminúria/diagnóstico , Albuminúria/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnósticoRESUMO
BACKGROUND: Serum proteomic analysis is an analytical technique utilizing high-throughput mass spectrometry (MS) in order to assay thousands of serum proteins simultaneously. The resultant 'proteomic signature' has been used to differentiate benign and malignant diseases, enable disease prognosis, and monitor response to therapy. OBJECTIVES: This pilot study was designed to determine if serum protein patterns could be used to distinguish patients with tumour-stage mycosis fungoides (MF) from patients with a benign inflammatory skin condition (psoriasis) and/or subjects with healthy skin. METHODS: Serum was analysed from 45 patients with tumour-stage MF, 56 patients with psoriasis, and 47 controls using two MS platforms of differing resolution. An artificial intelligence-based classification model was constructed to predict the presence of the disease state based on the serum proteomic signature. RESULTS: Based on data from an independent testing set (14-16 subjects in each group), MF was distinguished from psoriasis with 78.6% (or 78.6%) sensitivity and 86.7% (or 93.8%) specificity, while sera from patients with psoriasis were distinguished from those of nonaffected controls with 86.7% (or 93.8%) sensitivity and 75.0% (or 76.9%) specificity (depending on the MS platform used). MF was distinguished from unaffected controls with 61.5% (or 71.4%) sensitivity and 91.7% (or 92.9%) specificity. In addition, a secondary survival analysis using 11 MS peaks identified significant survival differences between two MF groups (all P-values <0.05). CONCLUSIONS: Serum proteomics should be further investigated for its potential to identify patients with neoplastic skin disease and its ability to determine disease prognosis.
Assuntos
Proteínas Sanguíneas/química , Micose Fungoide/sangue , Psoríase/sangue , Neoplasias Cutâneas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/diagnóstico , Projetos Piloto , Proteômica/métodos , Psoríase/diagnóstico , Sensibilidade e Especificidade , Neoplasias Cutâneas/diagnósticoRESUMO
Initial presentation of a malignant disease as recurrent attacks of lower limb ischaemia due to emboli from a mural thrombus in the descending thoracic aorta is extremely rare. A diagnosis of malignancy may thus easily be overlooked. Recent advances in imaging technology have made the diagnosis of thoracic aortic mural thrombi much easier. Occult malignancy should always be suspected in the absence of biochemical evidence of hypercoagulability. We report on a patient with underlying malignant disease who presented with lower limb ischaemia that was relieved by axillobifemoral bypass.
Assuntos
Aorta Abdominal/diagnóstico por imagem , Aorta Torácica/cirurgia , Artéria Femoral/cirurgia , Neoplasias Primárias Desconhecidas/complicações , Trombose/etiologia , Aorta Torácica/diagnóstico por imagem , Artéria Axilar/cirurgia , Prótese Vascular , Artéria Femoral/diagnóstico por imagem , Humanos , Isquemia/etiologia , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Radiografia , Recidiva , Procedimentos Cirúrgicos VascularesRESUMO
BACKGROUND: CC chemokine receptor-7 (CCR7), which plays a critical role in the migration of activated dendritic cells to regional lymph nodes via afferent lymphatic vessels, is also expressed by human breast and melanoma cell lines. Because neoplastic cells also enter lymphatic vessels before metastasis to the lymph nodes, we investigated whether CCR7 expression enhances metastasis of B16 murine melanoma cells to regional lymph nodes. METHODS: B16 cells were transduced with a retroviral vector containing CCR7 complementary DNA (CCR7-B16 cells) or with vector alone (pLNCX2-B16 control cells). The functional assay for CCR7 protein was Ca(2+) flux stimulated by the chemokine CCL21, a CCR7-specific ligand produced by lymphatic endothelial cells. B16 tumor cells were injected into the footpad of mice. Tumor cell metastasis to draining lymph nodes was assessed by measuring messenger RNA (mRNA) for tyrosinase-related protein-1 (TRP), a melanocyte-specific enzyme, with real-time, quantitative reverse transcription-coupled polymerase chain reaction. All statistical tests were two-sided. RESULTS: One week after injection into the footpad, 701-fold (95% confidence interval [CI] = 64- to 1336-fold) more TRP mRNA was detected in draining lymph nodes from CCR7-B16 cell-injected mice than in those from control cell-injected mice. Three weeks after footpad injection, 58% (11 of 19) of the draining lymph nodes from CCR7-B16 cell-injected mice and 5% (one of 19) of those from control mice showed gross metastases (P<.001). CCR7-B16 cells isolated from lymph node metastases retained functional CCR7 expression. Lymph node metastasis of CCR7-B16 cells was blocked by neutralizing anti-CCL21 antibodies (metastasis in none of five lymph nodes) but not by control immunoglobulin G (three of five). Enhanced metastasis of CCR7-B16 cells was specific for a lymphatic route because both CCR7-B16 and control cells co-injected intravenously metastasized to the lung at the same frequency. CONCLUSION: Expression of a single chemokine receptor gene, CCR7, increased B16 cell metastasis to draining lymph nodes, suggesting that cancer cells may co-opt normal mechanisms of lymph node homing during metastasis.
Assuntos
Metástase Linfática , Melanoma Experimental/patologia , Receptores de Quimiocinas/fisiologia , Animais , Quimiocina CCL21 , Quimiocinas CC/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores CCR7 , Receptores de Quimiocinas/genética , Células Tumorais CultivadasRESUMO
The binding of a T cell to an Ag-laden dendritic cell (DC) is a critical step of the acquired immune response. Herein, we address whether a DC-produced chemokine can induce the arrest of T cells on DC under dynamic flow conditions. Ag-primed T cells and a T cell line were observed to rapidly ( approximately 0.5 s) bind to immobilized DC at low shear stress (0.1-0.2 dynes/cm(2)) in a pertussis toxin-sensitive fashion. Quantitatively, Ag-primed T cells displayed 2- to 3-fold enhanced binding to DC compared with unprimed T cells (p < 0.01). In contrast to naive T cells, primed T cell arrest was largely inhibited by pertussis toxin, neutralization of the CC chemokine, macrophage-derived chemokine (CCL22), or by desensitization of the CCL22 receptor, CCR4. Our results demonstrate that DC-derived CCL22 induces rapid binding of activated T cells under dynamic conditions and that Ag-primed and naive T cells fundamentally differ with respect to chemokine-dependent binding to DC.
Assuntos
Células Dendríticas/fisiologia , Receptores de Quimiocinas/fisiologia , Linfócitos T/fisiologia , Animais , Antígenos CD40/fisiologia , Comunicação Celular , Linhagem Celular , Quimiocina CCL22 , Quimiocinas CC/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Receptores CCR4RESUMO
Although aberrations in adhesion molecule expression by lymphoma cells have been reported, the functional consequences of these changes are unclear. Herein, we report a patient with Sézary syndrome whose malignant peripheral blood T cells were TCRVbeta17+. Malignant T cell adhesion molecule abnormalities included an 80% downregulation of LFA-1 compared with normal controls and no detectable expression of alpha4 integrin. Under shear stress conditions, malignant T cells failed to arrest on recombinant ICAM-1 in the presence of chemokines and displayed an 80% decrease in the ability to arrest on TNF-alpha activated dermal microvascular endothelial cells compared with normal CD4+ memory T cells. Cutaneous lymphocyte-associated antigen expression was detected in approximately 25% of malignant T cells in the peripheral blood, but was substantially less than this in TCRVbeta17+ T cells in the dermis. By contrast, > 95% of malignant T cells in peripheral blood expressed L-selectin (CD62L), and L-selectin ligand was detected in dermal blood vessels at affected skin sites. Compared with normal CD4+, malignant T cells attached and rolled 6-fold more efficiently on L-selectin ligand (p < 0.0001). Thus, despite aberrant expression of LFA-1 and functional defects in the ability to arrest on activated endothelial cells, malignant T cells in this patient entered skin and produced significant clinical disease. We propose a mechanism by which the upregulated expression of L-selectin and L-selectin ligands may partially compensate for altered LFA-1 function.
Assuntos
Moléculas de Adesão Celular/metabolismo , Síndrome de Sézary/metabolismo , Neoplasias Cutâneas/metabolismo , Idoso , Antígenos CD18/metabolismo , Adesão Celular , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Feminino , Humanos , Molécula 1 de Adesão Intercelular/farmacologia , Selectina L/metabolismo , Ligantes , Antígeno-1 Associado à Função Linfocitária/metabolismo , Microcirculação , Receptores de Quimiocinas/metabolismo , Proteínas Recombinantes/farmacologia , Síndrome de Sézary/patologia , Síndrome de Sézary/fisiopatologia , Pele/irrigação sanguínea , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/fisiopatologia , Estresse Mecânico , Linfócitos T/fisiologiaRESUMO
Although many individual components of the lymphocyte's migratory machinery have been identified and analyzed for function in vitro, interesting questions remain regarding the in vivo integration of these components. How does the lymphocyte "choose" a direction for migration in the complex cytokine/chemokine environment of inflamed dermis when multiple chemokines secreted by multiple cell types are present? Can differences in chemokine expression explain the clinical and histologic differences seen in different inflammatory skin disease? What are the roles of proteins such as VAP-1? Our present understanding of lymphocyte migration has already led to the use of monoclonal antibodies to integrins such as LFA-1 that can potentially be of therapeutic use in skin diseases such as psoriasis. Small molecule inhibitors of T lymphocyte-specific receptors such as CCR4 or CXCR3 are promising agents for controlling T cell-mediated inflammation but have yet to be developed. These receptors may have greater selective expression on skin-homing T cells and thus may decrease the risk of iatrogenic immunosuppression. Close cooperation between the pharmaceutical industry and basic scientists will hopefully lead to the evolution of such compounds and toward more effective treatment of inflammatory skin diseases.
Assuntos
Receptores de Retorno de Linfócitos/imunologia , Dermatopatias/imunologia , Pele/imunologia , Linfócitos T/fisiologia , Anticorpos Monoclonais/fisiologia , Proteínas Reguladoras de Apoptose , Movimento Celular/fisiologia , Dermatite Atópica/imunologia , Endotélio Vascular/fisiologia , Humanos , Integrinas/fisiologia , Linfoma Cutâneo de Células T/imunologia , Metaloendopeptidases/fisiologia , Psoríase/imunologia , Psoríase/terapia , Receptores de Quimiocinas/imunologia , Receptores de Citocinas/imunologia , Dermatopatias/terapia , Neoplasias Cutâneas/imunologiaRESUMO
Chemokine receptors on dendritic cells (DC) and chemokines within lymph nodes (LN) contribute to trafficking of DC to appropriate sites within the LN. Here we show that DC that have migrated out of skin ex vivo (migratory DC, migDC) express 50-fold more CXCR5 mRNA than fresh Langerhans cells and migrate in response to B lymphocyte chemoattractant (BLC) in vitro. When injected into the footpad of mice, migDC emigrate to regional LN where up to 40% are found in B cell zones. By contrast, murine bone marrow-derived DC display 14-fold less CXCR5, do not migrate to BLC in vitro, and migrate strictly to T cell zones in LN. We propose that activated skin DC utilize CXCR5 and BLC as a possible mechanism to home to B cell zones of LN, where they may have direct effects on B cells.
Assuntos
Linfócitos B/citologia , Quimiocinas CXC/farmacologia , Quimiotaxia/efeitos dos fármacos , Células Dendríticas/imunologia , Linfonodos/citologia , Receptores de Citocinas/metabolismo , Pele/citologia , Animais , Linfócitos B/imunologia , Comunicação Celular , Quimiocina CXCL13 , Células Dendríticas/química , Feminino , Linfonodos/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Receptores CXCR5 , Receptores de Quimiocinas , Pele/imunologia , Organismos Livres de Patógenos Específicos , Linfócitos T/citologiaRESUMO
Mast cells (MC) are anatomically located near nerves and blood vessels in skin and the gastrointestinal tract and tend to localize within certain cutaneous tumors such as neurofibromas. However, the molecular mechanisms by which MC home to these sites are not well characterized. Fractalkine (FK) is a membrane-bound CX3C chemokine that displays constitutive expression in dendritic cells as well as in non-hematopoietic tissues including mammalian brain. Here we show that FK is constitutively expressed by skin endothelial cells, dermal dendrocytes and cells within neurofibromas. By reverse transcription-PCR, FK receptor, CX3CR1, is expressed by cultured murine bone marrow-derived MC (BMMC) of both connective tissue and mucosal phenotypes. Non-activated human dermal MC isolated from neonatal foreskin similarly demonstrated CX3CR1 expression. In chemotaxis assays, FK attracted MC with maximal migration occurring between 25 - 125 ng / ml. BMMC were not stimulated to release proinflammatory mediators in the presence of FK as measured by granule-associated beta-hexosaminidase release. Thus, CX3CR1 is expressed by MC and effectively mediates chemotaxis without inducing degranulation. We propose that the constitutive expression of FK on certain cells in the skin may be a factor in the tissue-specific homing of MC.
Assuntos
Degranulação Celular , Quimiocinas CX3C , Quimiocinas CXC/fisiologia , Mastócitos/fisiologia , Proteínas de Membrana/fisiologia , Pele/citologia , Animais , Receptor 1 de Quimiocina CX3C , Adesão Celular , Quimiocina CX3CL1 , Quimiocinas CXC/análise , Quimiotaxia , Feminino , Humanos , Proteínas de Membrana/análise , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/análise , Receptores de Citocinas/genética , Receptores de HIV/genéticaRESUMO
The lone CX3C chemokine, fractalkine (FK), is expressed in a membrane-bound form on activated endothelial cells and mediates attachment and firm adhesion of T cells, monocytes and NK cells. We now show that FK is associated with dendritic cells (DC) in epidermis and lymphoid organs. In normal human skin, dual-color fluorescence microscopy co-localized FK expression with Langerhans cells expressing CD1a. In tonsil, FK-positive DC expressed CD83, a marker for mature DC. Human and murine cultured DC up-regulated FK mRNA expression with maturation. Furthermore, CD40 ligation, but not TNF-alpha or lipopolysaccharide treatment, of activated, migratory DC that had migrated from skin explants resulted in a 2.5-fold increase of surface expression of FK without significant alterations of expression of CD80, CD86, CD54 or MHC class II. Since FK mediates adhesion of T cells to activated endothelial cells, the increased expression of FK during DC maturation (and particularly by CD40 ligation) may play a role in the ability of T cells and mature DC to form conjugates and engage in cell-cell communication.
Assuntos
Quimiocinas CX3C , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Células Dendríticas/imunologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Animais , Sequência de Bases , Ligante de CD40 , Adesão Celular/imunologia , Comunicação Celular/imunologia , Diferenciação Celular/imunologia , Linhagem Celular , Quimiocina CX3CL1 , Primers do DNA/genética , Células Dendríticas/citologia , Humanos , Células de Langerhans/imunologia , Melanócitos/imunologia , Glicoproteínas de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Tonsila Palatina/citologia , Tonsila Palatina/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/citologia , Pele/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/farmacologia , Regulação para CimaRESUMO
Dendritic cells (DCs) emigrate to regional lymph nodes (LNs) during immune responses via afferent lymphatic channels. Secondary lymphoid-tissue chemokine (SLC), a CC chemokine, is expressed in secondary lymphoid organs and mediates the chemotaxis of lymphocytes and DCs via its receptor, CC chemokine receptor 7 (CCR7). By dual-label fluorescence confocal microscopy, we showed MHC class II-positive cells within SLC-staining lymphatic channels in the mouse dermis. SLC was a potent in vitro chemoattractant for cultured, migratory skin DCs, and it enhanced the emigration of MHC class II-positive DCs from mouse skin explants by an average of 2.5-fold. Mature or cytokine-activated, but not resting, Langerhans cells expressed CCR7 mRNA by RT-PCR. Anti-SLC Abs, but not control or anti-eotaxin Abs, blocked the in vivo migration of 51Cr-labeled, skin-derived DCs from footpads to draining LNs by 50% (n = 9, p < 0. 005). Thus, we provide direct evidence that SLC and CCR7 participate in the emigration of DCs from peripheral tissue to LNs via lymphatics.
Assuntos
Quimiocinas CC/fisiologia , Células Dendríticas/fisiologia , Linfonodos/imunologia , Receptores de Quimiocinas/fisiologia , Pele/imunologia , Animais , Movimento Celular , Quimiocina CCL21 , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Receptores CCR7 , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: Most patients with erythrodermic cutaneous T-cell lymphoma (CTCL) have intense, generalized, refractory pruritus. In some large series the median survival was approximately 3 years. OBJECTIVE: Our purpose was to review our experience with methotrexate in the treatment of 29 patients with erythrodermic CTCL observed for up to 129 months. METHODS: This is a retrospective study. Data are presented in terms of response rates, freedom from treatment failure, and overall survival. RESULTS: Twelve patients (41%) achieved complete remission, and five (17%) achieved partial remission for a total response rate of 58%. The median freedom from treatment failure was 31 months, and the median survival was 8.4 years. Side effects caused treatment failure in only two patients. CONCLUSION: Low-dose methotrexate is a valuable first-line treatment for the majority of patients with early to intermediate-stage erythordermic CTCL.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Linfoma Cutâneo de Células T/tratamento farmacológico , Metotrexato/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Dermatite Esfoliativa/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prurido/tratamento farmacológico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Import of authentic or artificial precursor proteins into the matrix of isolated yeast mitochondria can proceed via a translocation intermediate that is lodged between the two mitochondrial membranes. The intermediate accumulates when import is arrested by depleting mitochondria of ATP. Generation of the intermediate requires a potential across the inner membrane. The intermediate is membrane-bound, partly or completely processed (depending on the precursor), and chased into the matrix by added ATP. This chase does not require a potential across the inner membrane. The properties of this intermediate support the proposal (Hwang, S., Jascur, J., Vestweber, D., Pon, L., and Schatz, G. (1989) J. Cell Biol. 109, 487-493) that import into the matrix involves two distinct translocation systems in the outer and the inner mitochondrial membrane that are not permanently coupled to each other. Only translocation across the inner membrane requires ATP in the matrix.
Assuntos
Proteínas Fúngicas/metabolismo , Membranas Intracelulares/metabolismo , Mitocôndrias/metabolismo , Precursores de Proteínas/metabolismo , Trifosfato de Adenosina/metabolismo , Transporte Biológico Ativo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Endopeptidases/farmacologia , Proteínas de Choque Térmico/metabolismo , Concentração de Íons de Hidrogênio , Proteínas de Membrana/metabolismo , Conformação Proteica , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiaeRESUMO
Leiomyoblastomas are rare tumors, and there have been few reports on their fine-needle aspiration (FNA) cytologic morphology. We herein describe the FNA features of a gastric leiomyoblastoma with subcutaneous metastasis. The cells had eosinophilic cytoplasm and oval eccentric nuclei, occasionally with intranuclear cytoplasmic inclusions. An organoid pattern was obvious in cell block sections. The tumor was positive for vimentin but negative for desmin, S-100 protein, and the common epithelial markers. The histogenesis is discussed, as are reasons why this tumor is better termed epithelioid mesenchymal tumor.
Assuntos
Biópsia por Agulha , Leiomioma/patologia , Neoplasias Gástricas/patologia , Idoso , Núcleo Celular/patologia , Citoplasma/patologia , Humanos , Imuno-Histoquímica , Leiomioma/secundário , Masculino , Metástase Neoplásica , Vimentina/análiseRESUMO
Work in several laboratories has established that import of proteins across the mitochondrial inner membrane requires an electrochemical potential across that membrane and cleavage of nucleoside triphosphate. We now show that nucleoside triphosphate must be present inside the inner membrane. In contrast, the potential-independent insertion of porin into the outer membrane requires ATP only outside the inner membrane.