RESUMO
OBJECTIVE: The complement cascade, especially the alternative pathway of complement, has been shown in basic research to be associated with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). We aimed to elucidate relationships between serum complement components and clinical characteristics in AAV. METHOD: In a nationwide prospective cohort study (RemIT-JAV-RPGN), we measured the serum levels of C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, factor B, factor D, factor H, factor I, mannose-binding lectin, and properdin in 52 patients with microscopic polyangiitis (MPA) and 39 patients with granulomatosis with polyangiitis (GPA). RESULTS: The properdin level of MPA and GPA was significantly lower than that of healthy donors. The properdin level was negatively correlated with the Birmingham Vasculitis Activity Score (BVAS) (ρ = -0.2148, p = 0.0409). The factor D level at 6 months was significantly positively correlated with the Vasculitis Damage Index (VDI) at 6, 12, and 24 months (ρ = 0.4207, 0.4132, and 0.3115, respectively). Patients with a higher ratio of C5a to C5 had higher neutrophil percentage and serum immunoglobulin G levels, and significantly lower creatinine levels. Cluster analysis divided the MPA and GPA patients into three subgroups. A principal component (PC) analysis aggregated 15 types of complements into alternative pathway-related PC 1 and complement classical pathway and common pathway-related PC 2. CONCLUSIONS: The serum levels of properdin and factor D were correlated with the BVAS and the VDI in MPA and GPA, respectively. Our analyses suggested the pathological heterogeneity of MPA and GPA from the aspect of complement components.
Assuntos
Proteínas do Sistema Complemento/metabolismo , Granulomatose com Poliangiite/sangue , Poliangiite Microscópica/sangue , Idoso , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/etiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Poliangiite Microscópica/tratamento farmacológico , Poliangiite Microscópica/etiologia , Pessoa de Meia-Idade , Análise de Componente Principal , Estudos Prospectivos , Recidiva , Indução de RemissãoRESUMO
OBJECTIVES: We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants. METHODS: SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA. RESULTS: S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with (n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement (n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers. CONCLUSION: HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.
Assuntos
Antirreumáticos/uso terapêutico , Calgranulina A/sangue , Calgranulina B/sangue , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Lúpus Eritematoso Cutâneo/sangue , Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/sangue , Nefrite Lúpica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Medula Óssea/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Células-Tronco Neoplásicas/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Linhagem Celular Tumoral , Regulação Leucêmica da Expressão Gênica , Células HL-60 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células K562 , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Camundongos , Neoplasia Residual/etiologia , Neoplasia Residual/genética , Neoplasia Residual/metabolismo , Células-Tronco Neoplásicas/patologia , Células U937 , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Evans syndrome is a rare autoimmune disorder with unknown aetiology. Although corticosteroids and/or intravenous immunoglobulin (IVIG) are commonly used in its treatment, no standard strategy has been established. We report here a 44-year-old male with refractory Evans syndrome combined with systemic lupus erythematosus (SLE) who responded well to rituximab. He was admitted to our hospital with severe bleeding caused by worsening of Evans syndrome. Despite treatment with a high-dose corticosteroid and IVIG, his thrombocytopaenia and haemolytic anaemia did not improve. We started rituximab at a dose of 375 mg/m(2) once a week for a total of two doses. There was significant improvement in his thrombocytopaenia and anaemia 1 month after administration of rituximab. Although the total immunoglobulin G (IgG) level did not change, the titres of platelet-associated IgG (PA-IgG) and of an indirect antiglobulin test (IAT) decreased under the treatment with rituximab. It is suggested that rituximab would be a powerful candidate in the treatment of refractory Evans syndrome by depleting abnormal clone-producing autoantibody.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Anticorpos Monoclonais Murinos , Doenças Autoimunes/complicações , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Masculino , Rituximab , SíndromeRESUMO
The thymus contains many apoptotic cells that arise from the process of positive and negative selection. Both thymic macrophages and thymic nurse cells/nursing thymic epithelial cells (nursing TECs), non-professional phagocytes, recognize and ingest apoptotic cells without inflammation or tissue damage. Previously we reported that human scavenger receptor class B (SR-B1) is involved in recognition of apoptotic thymocytes by nursing TECs. In this study, we examined the expression and role of a phosphatidylserine receptor (PSR). This receptor is believed to participate in the clearance of apoptotic cells. PSR was strongly expressed in nursing TECs. Transforming growth factor-beta augmented the expression of PSR leading to enhanced binding of apoptotic cells to nursing TECs. In nursing TECs, suppressed expression of human SR-B1 with anti-PSR antibody decreased binding of apoptotic thymocytes to nursing TECs. Our results suggest that both PSR and SR-B1 are expressed in nursing TECs and these receptors appear to play a major role in the clearance of apoptotic cells from the thymus.
Assuntos
Apoptose/fisiologia , Lipoproteínas HDL/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Lipoproteínas/metabolismo , Timo/citologia , Timo/metabolismo , Animais , Células Cultivadas , Citocinas/farmacologia , Células Epiteliais/metabolismo , Feminino , Humanos , Histona Desmetilases com o Domínio Jumonji , Lipoproteínas HDL/genética , Camundongos , Camundongos Endogâmicos BALB C , Oligonucleotídeos Antissenso/farmacologia , Receptores de Superfície Celular/genética , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Receptores de Lipoproteínas/genética , Receptores Depuradores , Receptores Depuradores Classe B , Timo/efeitos dos fármacosRESUMO
Menin is a protein encoded by the gene mutated in multiple endocrine neoplasia type 1 (MEN1) characterized by multiple endocrine tumors of the parathyroid glands, pancreatic islets and the anterior pituitary, especially prolactinoma. In this study, we examined the effects of menin on human prolactin (hPRL) expression. In rat pituitary GH3 cells stably expressing menin, both PRL gene expression/secretion and thymidine incorporation into DNA were inhibited as compared with mock-transfected cells. The transcriptional activity of PRL promoter in GH3 cells co-transfected with menin was significantly decreased. A deletion mutation (569 delC), which we identified in a Japanese MEN1 family, was introduced into menin. When GH3 cells were transfected with a mutant menin expression vector, inhibition of hPRL promoter activity was partially reversed. These observations suggest that menin inhibits hPRL promoter activity and cell proliferation, raising the possibility that menin might play an important role in the tumorigenesis of prolactinoma.
Assuntos
Regulação para Baixo , Proteínas de Neoplasias/metabolismo , Prolactina/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas , Animais , Western Blotting , Divisão Celular , Linhagem Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasia Endócrina Múltipla Tipo 1/genética , Proteínas de Neoplasias/genética , Prolactina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Transcrição Gênica , TransfecçãoRESUMO
There are few reports which describe the association of polymyositis/dermatomyositis (PM/DM) and silicosis. The purpose of this study is to describe the clinical features of PM/DM associated with silicosis. We first describe clinical features of two cases and provide a review of the literature. Finally, seven patients with PM/DM associated with silicosis are retrospectively evaluated. There were one female and six males. Histological specimens were obtained by open lung biopsy in five cases and not examined in two. The mechanism of the association between silicosis and PM/DM is discussed.
Assuntos
Polimiosite/complicações , Polimiosite/diagnóstico , Silicose/complicações , Silicose/diagnóstico , Biópsia por Agulha , Análise Química do Sangue , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Tomografia Computadorizada por Raios XAssuntos
Glucocorticoides/farmacologia , Hormônio do Crescimento Humano/farmacologia , Proteínas do Leite , Proteínas Proto-Oncogênicas , Linfócitos T/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Relação CD4-CD8 , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Divisão Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Dexametasona/farmacologia , Expressão Gênica/efeitos dos fármacos , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Janus Quinase 2 , Fosforilação , Fosfotirosina/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/análise , Receptores da Somatotropina/genética , Fator de Transcrição STAT5 , Linfócitos T/metabolismo , Transativadores/metabolismoRESUMO
We investigated the function of CD56+ CD8+ T cells (CD56+ T cells) and CD56- CD57+ CD8+ T cells (CD57+ T cells; natural killer (NK)-type T cells) and compared them with those of normal CD56- CD57- CD8+ T cells (CD8+ T cells) and CD56+ NK cells from healthy volunteers. After the stimulation with immobilized anti-CD3 antibodies, both NK-type T cells produced much larger amounts of interferon-gamma (IFN-gamma) than CD8+ T cells. Both NK-type T cells also acquired a more potent cytotoxicity against NK-sensitive K562 cells than CD8+ T cells while only CD56+ T cells showed a potent cytotoxicity against NK-resistant Raji cells. After the stimulation with a combination of interleukin (IL)-2, IL-12 and IL-15, the IFN-gamma amounts produced were NK cells > or = CD56+ T cells > or = CD57+ T cells > CD8+ T cells. The cytotoxicities against K562 cells were NK cells > CD56+ T cells > or = CD57+ T cells > CD8+ T cells while cytotoxicities against Raji cells were CD56+ T cells > CD57+ T cells > or = CD8+ T cells > or = NK cells. However, the CD3-stimulated proliferation of both NK-type T cells was smaller than that of CD8+ T cells partly because NK-type T cells were susceptible to apoptosis. In addition to NK cells, NK-type T cells but not CD8+ T cells stimulated with cytokines, expressed cytoplasmic perforin and granzyme B. Furthermore, CD3-stimulated IFN-gamma production from peripheral blood mononuclear cells (PBMC) correlated with the proportions of CD57+ T cells in PBMC from donors. Our findings suggest that NK-type T cells play an important role in the T helper 1 responses and the immunological changes associated with ageing.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Apoptose/imunologia , Complexo CD3/imunologia , Antígeno CD56/análise , Antígenos CD57/análise , Técnicas de Cultura de Células , Divisão Celular/imunologia , Criança , Citotoxicidade Imunológica , Granzimas , Humanos , Imunofenotipagem , Interferon gama/biossíntese , Células K562/imunologia , Ativação Linfocitária/imunologia , Glicoproteínas de Membrana/metabolismo , Perforina , Proteínas Citotóxicas Formadoras de Poros , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Serina Endopeptidases/metabolismo , Células Tumorais CultivadasRESUMO
OBJECTIVE: Growth hormone (GH) has been reported to have a potent effect on the immune system. However, the detailed mechanism of the effect of GH on the immune system has not yet been clarified. This study was designed to investigate the nature of this mechanism. METHODS: In the present study, we investigated the effects of GH on the susceptibility of both human CEM/C7 lymphocytes and human IM-9 lymphocytes to Fas-induced apoptosis. RESULTS: Both cell lines expressed GH receptor mRNA. GH rescued Fas-induced suppression of [(3)H]-thymidine incorporation into each cell line. GH prevented Fas-induced apoptosis in each cell line without changing Fas antigen expression. We next investigated the mechanisms of the prevention of Fas-induced apoptosis, by focusing on intracellular molecules related to the apoptotic signal. Bcl-2 expression was increased by GH treatment in both CEM/C7 and IM-9 lymphocytes. GH also downregulated caspase-3 expression and inhibited activation of caspase-3 in both cell lines. CONCLUSION: These findings suggest that GH regulates the human immune system through inhibition of Fas-induced apoptosis in activated T and B lymphocytes.
Assuntos
Apoptose/imunologia , Sistema Endócrino/imunologia , Hormônio do Crescimento/imunologia , Sistema Imunitário/imunologia , Tolerância Imunológica/imunologia , Linfócitos/imunologia , Receptor fas/imunologia , Anticorpos Monoclonais/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3 , Caspases/genética , Caspases/imunologia , Caspases/metabolismo , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Sistema Endócrino/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Hormônio do Crescimento/farmacologia , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Receptores da Somatotropina/genética , Receptores da Somatotropina/imunologia , Células Tumorais Cultivadas , Receptor fas/efeitos dos fármacosRESUMO
Polymyositis is an inflammatory muscle disease with unknown cause that is characterized by progressive weakness of the proximal muscles. Limited information is available concerning the effectiveness of the combination therapy with cyclosporine A and methotrexate in reducing myositis activity. We describe here a female patient with polymyositis who showed resistance to pulse corticosteroid therapy. Neither the combination of azathioprine (100 mg/day) nor methotrexate (10 mg/week) with corticosteroids decreased the value of creatine phosphokinase. Normalization of the creatine phosphokinase level as well as improvement of muscle strength was obtained only when low-dose cyclosporine A (3 mg/kg/day) was combined with methotrexate.
Assuntos
Antirreumáticos/uso terapêutico , Ciclosporina/uso terapêutico , Metotrexato/uso terapêutico , Polimiosite/tratamento farmacológico , Creatina Quinase/sangue , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Debilidade Muscular/tratamento farmacológico , Polimiosite/sangue , Resultado do TratamentoAssuntos
Relação CD4-CD8 , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Hormônio do Crescimento/farmacologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Baço/imunologia , Animais , Corticosterona/antagonistas & inibidores , Corticosterona/sangue , Ingestão de Alimentos/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Masculino , Ratos , Ratos Wistar , Baço/citologia , Aumento de Peso/efeitos dos fármacosRESUMO
We report an interesting case of a 47-yr-old who had a large goiter and multiple rib tumors. The patient was initially suspected of having thyroid cancer, which had metastasized on the ribs, based on imaging studies. However, laboratory tests revealed a high level of ionized calcium and parathyroid hormone (PTH). The large goiter was diagnosed as having parathyroid tumors owing to the high level of PTH in the tissue fluid. The biopsy specimen from a rib tumor was diagnosed as containing brown tumors associated with primary hyperparathyroidism (PHP). The patient also had prolactinoma and pancreatic gastrinoma. Her daughter had both prolactinoma and PHP, and her brother and her father had PHP. Thus, the patient was diagnosed as having multiple endocrine neoplasia type 1.
Assuntos
Neoplasias Ósseas/diagnóstico , Bócio/diagnóstico , Neoplasias das Paratireoides/diagnóstico , Costelas , Adulto , Neoplasias Ósseas/etiologia , Neoplasias Ósseas/patologia , Cálcio/sangue , Diagnóstico Diferencial , Feminino , Gastrinoma/complicações , Gastrinoma/diagnóstico , Humanos , Hiperparatireoidismo/complicações , Hiperparatireoidismo/diagnóstico , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Hormônio Paratireóideo/análise , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/química , Neoplasias das Paratireoides/complicações , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/complicações , Prolactinoma/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
The liver remains a hematopoietic organ after birth and can produce all leukocyte lineages from resident hematopoietic stem cells. Hepatocytes produce acute phase proteins and complement in bacterial infections. Liver Kupffer cells are activated by various bacterial stimuli, including bacterial lipopolysaccharide (LPS) and bacterial superantigens, and produce interleukin (IL)-12. IL-12 and other monokines (IL- 18 etc.) produced by Kupffer cells activate liver natural killer (NK) cells and NK1.1 Ag+ T cells to produce interferon-gamma and thereby acquire cytotoxicity against tumors and microbe-infected cells. These liver leukocytes and the T helper 1 immune responses induced by them thus play a crucial role in the first line of defense against bacterial infections and hematogenous tumor metastases. However, if this defense system is inadequately activated, shock associated with multiple organ failure takes place. Activated liver NK1.1 Ag+ T cells and NK cells also cause hepatocyte injury. NK1.1 Ag+ T cells and another T-cell subset with an intermediate T-cell receptor, CD 122+CD8+ T cells, can develop independently of thymic epithelial cells. Liver NK cells and NK1.1 Ag+ T cells physiologically develop in situ from their precursors, presumably due to bacterial antigens brought from the intestine via the portal vein. NK cells activated by bacterial superantigens or LPS are also probably involved in the vascular endothelial injury in Kawasaki disease.
Assuntos
Células Matadoras Naturais/imunologia , Células de Kupffer/imunologia , Fígado/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Antígenos de Bactérias/imunologia , Linhagem da Célula , Pré-Escolar , Concanavalina A/toxicidade , Bactérias Gram-Positivas/imunologia , Humanos , Absorção Intestinal , Células de Kupffer/metabolismo , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/toxicidade , Circulação Hepática , Ativação Linfocitária , Linfocinas/metabolismo , Ativação de Macrófagos , Camundongos , Camundongos SCID , Síndrome de Linfonodos Mucocutâneos/imunologia , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Metástase Neoplásica , Células Neoplásicas Circulantes , Peritonite/complicações , Peritonite/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/análise , Choque Séptico/complicações , Choque Séptico/imunologia , Fenômeno de Shwartzman/imunologia , Superantígenos/imunologia , Linfócitos T Citotóxicos/imunologia , Células Th1/imunologia , Células Th1/metabolismoRESUMO
OBJECTIVE: KL-6 is a mucin-like high molecular weight glycoprotein, which is strongly expressed on type II alveolar pneumocytes and bronchiolar epithelial cells. It has been demonstrated that the KL-6 antigen is a useful marker for estimating the activity of interstitial pneumonia. In this study, it is hypothesised that serum KL-6 is a useful marker to evaluate the activity of interstitial pneumonia associated with polymyositis/dermatomyositis (PM/DM). METHODS: KL-6 was measured in sera in 16 patients diagnosed with PM/DM. Five had non-specific interstitial pneumonia (NSIP), three had diffuse alveolar damage (DAD), and eight had no pulmonary involvement, and 10 were normal non-smokers as a control group. The correlation was also evaluated between the KL-6 level and each clinical course in patients with pulmonary involvement associated with PM/DM. Immunohistochemical analysis using monoclonal anti-KL-6 antibody was also performed. RESULTS: KL-6 concentrations in sera of patients with interstitial pneumonia associated with PM/DM were significantly high compared with those of PM/DM without interstitial pneumonia, and normal non-smokers. KL-6 concentrations in sera in patients with DAD significantly increased compared with those of other groups. KL-6 values in sera changed according to the progression or improvement of interstitial pneumonia. Immunohistochemical study using pulmonary tissues obtained from patients with DAD demonstrated that the hyaline membrane, proliferating type II pneumocytes, bronchial epithelial cells and some endothelial cells in pulmonary veins were stained by antihuman KL-6 antibody. CONCLUSION: These data demonstrate that measurement of serum KL-6 was a useful marker to evaluate the activity of acute interstitial pneumonia associated with PM/DM.
Assuntos
Dermatomiosite/complicações , Doenças Pulmonares Intersticiais/sangue , Mucinas/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Doença Aguda , Adulto , Idoso , Antígenos , Antígenos de Neoplasias , Biomarcadores/sangue , Dermatomiosite/sangue , Progressão da Doença , Feminino , Glicoproteínas , Humanos , Técnicas Imunoenzimáticas , Pulmão/metabolismo , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Mucina-1RESUMO
Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by the presence of gas-filled cysts in the submucosa or subserosa of gastrointestinal tract. PCI has been widely recognized as a late manifestation of systemic sclerosis but seldom reported to take place in patients with systemic lupus erythematosus (SLE). We reported here a 13-year-old female who had been diagnosed to have SLE based on the following findings; malar rash, discoid erythema, proteinuria, positive antinuclear antibody and anti-DNA antibody. She had been treated with various immunosuppressive drugs including pulse use of corticosteroid, cyclophosphamide and cyclosporin A. She was referred to our hospital because of proteinuria and numbness on her right fifth toe, refractory to above treatment. On admission, the activity of her disease was already low and she had no abdominal symptoms. Plain X-ray film showed multiple round translucencies along the wall of the ascending and transverse colon. Colonoscopy revealed multiple firm-walled cysts distributing in the terminal ileum as well. A diagnosis of PCI was made and she was successfully treated with oral antibiotics and laxatives. The association of PCI with SLE is reviewed briefly.
Assuntos
Lúpus Eritematoso Sistêmico/complicações , Pneumatose Cistoide Intestinal/etiologia , Adolescente , Colo/patologia , Feminino , Humanos , Pneumatose Cistoide Intestinal/patologiaRESUMO
Although bacterial superantigens have been well characterized as potent stimulators of T cells, their role in natural killer (NK)-type cells remains largely unknown. In the present study, we examined the effect of bacterial superantigens on mouse liver NK cells and NK1.1 Ag(+) (NK1(+)) T cells. C57BL/6 mice were intravenously injected with staphylococcal enterotoxin B (SEB) or streptococcal pyrogenic exotoxin A (SPE-A), and mononuclear cells (MNC) of various organs were obtained from mice 4 hours after being injected with superantigen. MNC were cultured for 48 hours, and interferon gamma (IFN-gamma) levels of supernatants were measured. The antitumor cytotoxicities of the liver and spleen MNC were also evaluated 24 hours after the mice were injected with superantigen. Liver MNC produced more IFN-gamma than did splenocytes, and peripheral blood and lung MNC did not produce any detectable IFN-gamma. In addition, liver MNC acquired a potent antitumor cytotoxicity by the SEB injection, and both NK cells and NK1(+)T cells but not cluster of differentiation (CD)8(+) T cells were responsible for the cytotoxicity as demonstrated by either in vivo or in vitro cell depletion experiments, and the NK-type cells were partly responsible for the increased serum IFN-gamma. Activation of liver NK-type cells was also supported by the fact that liver NK cells proportionally increased and NK1(+) T cells augmented their CD11a expressions after SEB injection. The pretreatment of mice with anti-IFN-gamma Ab and/or with anti-interleukin-12 (IL-12) Ab diminished the SEB-induced cytotoxicity of liver MNC. Furthermore, the in vivo depletion of Kupffer cells decreased the SEB-induced cytotoxicity of liver MNC. Consistent with these results, liver MNC stimulated with superantigens in the presence of Kupffer cells in vitro produced a greater amount of IFN-gamma than did the liver MNC without Kupffer cells or splenocytes. Our results suggest that bacterial superantigen-primed Kupffer cells produce IL-12 and other monokines, while also nonspecifically activating both NK cells and NK1(+) T cells to produce IFN-gamma.
Assuntos
Antígenos/análise , Proteínas de Bactérias , Células Matadoras Naturais/imunologia , Células de Kupffer/fisiologia , Ativação Linfocitária , Proteínas de Membrana , Proteínas/análise , Superantígenos/imunologia , Linfócitos T/imunologia , Animais , Antígenos Ly , Antígenos de Superfície , Células Cultivadas , Citotoxicidade Imunológica , Enterotoxinas/imunologia , Exotoxinas/imunologia , Citometria de Fluxo , Interferon gama/biossíntese , Interleucina-12/fisiologia , Lectinas Tipo C , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Subfamília B de Receptores Semelhantes a Lectina de Células NKAssuntos
Desenvolvimento Ósseo/fisiologia , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Hormônio do Crescimento/metabolismo , Crescimento/fisiologia , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Corticosterona/sangue , Relação Dose-Resposta a Droga , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Crescimento/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Ratos , Ratos Wistar , Baço/efeitos dos fármacos , Baço/fisiologiaRESUMO
Chloroethyl-nitrosourea (CENU) is one of the most potent chemotherapeutic agents for brain tumors. However, acquired resistance to this drug has become a serious problem in the treatment of brain tumor patients. The main mechanism of the resistance is a recruitment of the O6-methylguanine-DNA- methyltransferase (MGMT) in tumor cells. Many approaches, including treatment with enzyme-depletions, antibodies, antisenses, and a ribozyme, have been reported to successfully overcome the resistance. In order to evaluate these approaches properly, we designed a syngenic rat brain-tumor model resistant to CENU. The 9L rat gliosarcoma cells were retrovirally transduced with MGMT cDNA and stereotactically implanted into the brain parenchyma. In this model, rats inoculated with resistant cells died significantly earlier than did rats with control cells after treatment with CENU. Because of the limited intracranial space, the animals presented a restricted survival. Since the survival was sensitive and reproducible, this system may have a role in the evaluation of approaches to drug-resistant brain-tumors.