RESUMO
BACKGROUND AND PURPOSE: Obtaining information on invisible vasculature distal to the occlusion site helps to deploy a stent retriever safely during mechanical thrombectomy for large-vessel occlusion. It is essential to reduce the amount of contrast used for detecting the vessels distal to the occlusion site because acute ischemic stroke patients tend to have chronic kidney disease and patients with severe chronic kidney disease are at an increased risk of contrast-associated acute kidney injury. We assessed whether vessels distal to the occlusion site during acute ischemic stroke with large-vessel occlusion could be visualized on angiographic images using flat panel detector CT acquired following intra-arterial diluted contrast injection, compared with MRA findings. MATERIALS AND METHODS: Between May 2019 and January 2020, we enrolled 28 consecutive patients with large-vessel occlusions of the anterior circulation eligible for mechanical thrombectomy following MR imaging. The patients underwent CBV imaging using flat panel detector CT with an intra-arterial diluted contrast injection instead of intravenous injection. Flat panel detector CT angiographic images reconstructed from the same dataset were evaluated for image quality, collateral status of the MCA territory, and visualization of the vessels distal to the occlusion site. These findings were compared with MRA findings. RESULTS: Twenty-two patients were retrospectively examined. Flat panel detector CT angiographic image quality in 20 patients (91%) was excellent or good. The distal portion of the occluded vessel segment was visualized in 14 patients (70%), while the proximal portion of the segment adjacent to the occluded vessel in 3 (15%) was visualized. No visualization was observed in only 1 patient (5%) with no collateral supply. Flat panel detector CT angiographic images were shown to evaluate vessels distal to the occlusion site more accurately than MRA. CONCLUSIONS: In acute ischemic stroke with large-vessel occlusion, flat panel detector CT angiographic images could successfully visualize vessels distal to the occlusion site with a small amount of contrast material.
Assuntos
Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada/métodos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , Trombectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodosRESUMO
While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+ CD127- regulatory T cells (edu.Tregs ) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg ; anti-A/B antibodies were not involved in the Treg -mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Antígeno B7-H1/imunologia , Células Endoteliais/imunologia , Antígenos HLA-DR/imunologia , Isoanticorpos/imunologia , Transplante de Órgãos , Linfócitos T Reguladores/imunologia , Células Endoteliais/patologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Humanos , Linfócitos T Reguladores/patologiaRESUMO
BACKGROUND AND STUDY AIMS: To determine the clinical features associated with advanced duodenal and ampullary adenomas in familial adenomatous polyposis. Secondarily, we describe the prevalence and clinical significance of jejunal polyposis. PATIENTS AND METHODS: This is a single center, prospective study of 62 patients with familial adenomatous polyposis. Duodenal polyposis was classified according to Spigelman and ampullary adenomas were identified. Patients with Spigelman III and IV duodenal polyposis underwent balloon assisted enteroscopy. Predefined groups according to Spigelman and presence or not of ampullary adenomas were related to the clinical variables: gender, age, family history of familial adenomatous polyposis, type of colorectal surgery, and type of colorectal polyposis. RESULTS: Advanced duodenal polyposis was present in 13 patients (21â%; 9 male) at a mean age of 37.61â±â13.9 years. There was a statistically significant association between family history of the disease and groups according to Spigelman ( P â=â0.03). Seven unrelated patients (6 male) presented ampullary adenomas at a mean age of 36.14â±â14.2 years. The association between ampullary adenomas and extraintestinal manifestations was statistically significant in multivariate analysis ( P â=â0.009). Five endoscopic types of non-ampullary adenoma were identified, showing that lesions larger than 10âmm or with a central depression presented foci of high grade dysplasia. Among 28 patients in 12 different families, a similar Spigelman score was identified; 10/12 patients (83.3â%) who underwent enteroscopy presented small tubular adenomas with low grade dysplasia in the proximal jejunum. CONCLUSIONS: Advanced duodenal polyposis phenotype may be predictable from disease severity in a first-degree relative. Ampullary adenomas were independently associated with the presence of extraintestinal manifestations.
RESUMO
OBJECTIVES: Patients with peripheral facial palsy frequently complain of fluid leakage and food retention during meals. We investigated oral function during eating in adults with peripheral facial palsy. DESIGN: A prospective two-phase controlled observational study. SETTING: Data were collected at the ENT clinic in Nihon University Itabashi Hospital (patients) and Nihon University Dental Hospital (controls) between September 2009 and August 2011 and analysed at the Department of Oral Diagnostic Sciences in Nihon University School of Dentistry. PARTICIPANTS: Fourteen patients with acute idiopathic facial palsy and 14 controls completed Study 1. Sixteen patients with acute idiopathic facial palsy and 16 controls completed Study 2. MAIN OUTCOME MEASURES: In Study 1, oral vestibular cleansing capability was assessed by measuring the amount of rice remaining in the oral vestibule after mastication. In Study 2, masticatory efficiency was evaluated by measuring glucose eluted from gummy jelly during chewing. These oral functions were observed at the first visit and final visit (after patients with facial palsy had recovered). RESULTS: Oral vestibular cleansing capability at the first visit was significantly decreased by facial palsy (P < 0.001 versus healthy volunteers and P < 0.001 versus contralateral side) but recovered as facial muscular function improved (P = 0.034). There was a significant correlation between improvement in paralysis and decreased food retention (r = -0.528, P = 0.010). At the first visit, masticatory efficiency on the affected side was significantly lower than that of controls (P = 0.002) but had mostly recovered after resolution of facial palsy (P = 0.033). CONCLUSIONS: Oral functions were decreased by peripheral facial palsy. Oral vestibular cleansing capability was more significantly associated than masticatory efficiency with facial muscle function. Our data suggest that peripheral facial palsy impairs eating and worsens oral hygiene, which may result in oral disease.
Assuntos
Paralisia de Bell/fisiopatologia , Músculos Faciais/fisiopatologia , Mastigação/fisiologia , Músculos da Mastigação/fisiopatologia , Boca/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Adulto , Paralisia de Bell/complicações , Paralisia de Bell/terapia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Bucal , Estudos ProspectivosRESUMO
Hyperplastic gastric polyps are often found at GI endoscopy and are not considered premalignant lesions, although some cases of malignancy have been reported. Neuroendocrine tumors, conversely, are rare and account for approximately 1% to 2% of gastric polyps. Both hyperplastic gastric polyps and neuroendocrine tumors are related to gastric atrophy. The case of a hyperplastic polyp with multifocal areas of adenocarcinoma within the polyp associated to multiple gastric neuroendocrine tumors is reported.
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Adenocarcinoma/patologia , Transformação Celular Neoplásica/patologia , Gastrite Atrófica/patologia , Tumores Neuroendócrinos/patologia , Pólipos/patologia , Neoplasias Gástricas/patologia , Biópsia , Feminino , Gastrinas/sangue , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Humanos , Pessoa de Meia-IdadeRESUMO
We report a case of a 54-year-old man with T4N0M0 non-small cell lung cancer directly invading the thoracic wall and aortic arch. He underwent neoadjuvant chemotherapy followed by en bloc resection of the tumor, lung, chest wall and aortic arch. Perfusion was maintained through femoral-femoral cardiopulmonary bypass, with permanent bypass to the arch vessels to avoid separate extracorporeal cerebral circulation. Total reconstructions of the chest wall and aortic arch were completed without the need for cardiac arrest. The final pathological diagnosis was squamous cell carcinoma, T4N0M0. The patient was discharged without major complications and has been free of disease for 20 months postoperatively.
Assuntos
Aorta Torácica/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/cirurgia , Circulação Cerebrovascular , Neoplasias Pulmonares/cirurgia , Perfusão/métodos , Pneumonectomia , Procedimentos Cirúrgicos Vasculares , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , Aortografia/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/fisiopatologia , Quimioterapia Adjuvante , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Dysplasia and esophageal adenocarcinoma may arise in patients with Barrett's esophagus after fundoplication esophageal pH monitoring showing no acid in esophagus. This suggests the need to develop methodology to evaluate the occurrence of ultra-distal reflux (1cm above the LES). The objective of the study was to compare acid exposition in three different levels: 5cm above the upper border of the LES, 1cm above the LES and in the intrasphincteric region. Eleven patients with Barrett's esophagus after Nissen fundoplication with no clinical, endoscopic and radiologic evidence of reflux were selected. Four-channel pH monitoring took place: channel A, 5cm above the upper border of the LES; channel B, 1cm above the LES; channel C, intrasphincteric; channel D, intragastric. The results of channels A, B and C were compared. There was significant increase in number of reflux episodes and a higher fraction of time with pH <4.0 in channel B compared to channel A. There was significant decrease in fraction of time with pH <4.0 in channel B compared to channel C. Two cases of esophageal adenocarcinoma were diagnosed in the studied patients. The region 1cm above the upper border of the LES is more exposed to acid than the region 5cm above the upper border of the LES, although this exposure occurred in reduced levels. The region 1cm above the upper border of the LES is less exposed to acid than the intrasphincteric region.
Assuntos
Esôfago de Barrett/fisiopatologia , Esfíncter Esofágico Inferior/fisiologia , Refluxo Gastroesofágico/fisiopatologia , Monitorização Fisiológica/métodos , Adulto , Idoso , Esôfago de Barrett/cirurgia , Feminino , Fundoplicatura , Humanos , Concentração de Íons de Hidrogênio , Masculino , Manometria , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação , Adulto JovemRESUMO
OBJECTIVE: Only a few benign tumours of the middle ear have been reported to lead to the development of facial palsy. Here, we describe a patient with middle-ear cavernous lymphangioma and facial palsy. STUDY DESIGN: Single case study. PATIENT: A 61-year-old man presented with left-sided hearing impairment and incomplete left facial palsy. A tumour was confirmed to be occupying the epi- to mesotympanum and to be joined to the facial nerve. The tumour was removed along with facial nerve tissue, which was resected at its horizontal portion, and the remaining facial nerve was fixed by end-to-end anastomosis. Complete facial paralysis occurred after the operation, but the patient's House-Brackmann grade gradually improved to grade III. Post-operative histopathological examination revealed infiltration of the lymphangioma into the facial nerve tissue, together with mild neural atrophy of the facial nerve. CONCLUSION: These findings suggested that tumour invasion was the cause of facial palsy in this patient.
Assuntos
Neoplasias da Orelha/complicações , Orelha Média , Paralisia Facial/etiologia , Linfangioma/complicações , Neoplasias da Orelha/diagnóstico , Neoplasias da Orelha/cirurgia , Nervo Facial/patologia , Humanos , Linfangioma/diagnóstico , Linfangioma/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To assess the correlation between angiogenesis and Doppler signal intensity using transrectal colour Doppler ultrasonography (CDUS) in patients with prostate cancer. PATIENTS AND METHODS: The study comprised 56 patients who underwent radical prostatectomy and had untreated tumours with a volume of> 0.1 mL in the peripheral zone. CDUS images were recorded on videotape before surgery. The Doppler signal intensity in tumours was evaluated using the colour pixel intensity (PI). Microvessel density (MVD) and vascular endothelial growth factor (VEGF) immunoreactivity were determined in the prostatectomy specimens. Microvessels were identified by immunohistochemical staining of endothelial cells for CD31. RESULTS: The PI in the tumour correlated with MVD (P < 0.001) and increased with higher levels of VEGF immunoreactivity (P = 0.004). There was no correlation between Gleason score and MVD or PI in the tumour. CONCLUSION: Blood flow assessed by CDUS may reflect the state of angiogenesis in prostate cancer. CDUS may be a useful technique for predicting tumour progression or prognosis, and may be useful for monitoring the effects of anti-angiogenic agents in the future.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Neovascularização Patológica/diagnóstico por imagem , Neoplasias da Próstata/irrigação sanguínea , Adenocarcinoma/irrigação sanguínea , Idoso , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodosRESUMO
The changes in plasma concentrations of inhibins A, B and pro-alpha C were determined in the cyclic golden hamster during follicular atresia induced with antiserum against luteinizing hormone releasing hormone (LHRH-AS) at 1100 h on day 4 (day 1=day of ovulation). Follicular status in the ovary was also studied by determining the number of follicles ovulating in response to human chorionic gonadotrophin (hCG) injection. The time-courses of changes in plasma concentrations of inhibins A, B and pro-alpha C were different from each other during induced follicular atresia and subsequent follicular development. Plasma concentrations of inhibin A decreased to 58.6% of initial values by 24 h after LHRH-AS treatment, and then remained relatively low until at least 60 h later. Plasma concentrations of inhibin B decreased to 64.2% of the initial values by 18 h after LHRH-AS treatment and remained at basal values for 36 h, but increased abruptly to greater than initial values at 42 h after the treatment. Plasma concentrations of inhibin pro-alpha C increased at 6 and 12 h, decreased suddenly to 21.9% of the initial values by 24 h after LHRH-AS treatment, and then gradually increased until 60 h after LHRH-AS. The number of follicles responding to hCG decreased gradually between 0 and 30 h after LHRH-AS, when no ovulations were observed, and then gradually increased until 60 h. The changes in follicular ovulatory responses to hCG correlated with the plasma profile of inhibin A throughout the experiment. These results suggest that inhibin A is mainly secreted by large antral follicles. In contrast, during the subsequent follicular development, the plasma concentration of inhibin B increased earlier than that of inhibin A. These results suggest that inhibin B is secreted by small and large antral follicles. Plasma concentrations of inhibin pro-alpha C were high at a time when plasma concentrations of oestradiol-17 beta had already decreased, indicating that inhibin pro-alpha C is secreted not only from healthy follicles but also from early atretic antral follicles.
Assuntos
Atresia Folicular/fisiologia , Fase Folicular/fisiologia , Inibinas/metabolismo , Folículo Ovariano/metabolismo , Animais , Gonadotropina Coriônica/farmacologia , Cricetinae , Feminino , Hormônio Liberador de Gonadotropina/imunologia , Soros Imunes/administração & dosagem , Inibinas/sangue , Mesocricetus , Folículo Ovariano/efeitos dos fármacos , Precursores de Proteínas/sangue , Precursores de Proteínas/metabolismoRESUMO
Numerous antral follicles develop during the second half of pregnancy in the golden hamster. However, mechanisms regulating follicular development during this period are unknown. Because inhibin and activin are related to follicular development, these hormones were studied to gain insight into any potential roles in follicular development. Plasma inhibin A and B suddenly increased from day 8 of pregnancy, reached peak levels on day 10 and gradually declined to term. Plasma activin A gradually increased from day 8 to day 15 of pregnancy, and this was followed by an abrupt decrease at day one of lactation. Ovariectomy on day 12 of pregnancy rapidly reduced plasma inhibin A and B, but not activin A levels. Hysterectomy or placentectomy on day 12 of pregnancy caused an abrupt decrease in the levels of plasma activin A and FSH, but not inhibin A and B at 6 h after surgery. Hysterectomy also induced atresia of large antral follicles at 24 h after surgery. These results indicate that antral follicles are the main source of circulating inhibin A and B, whereas uteri and placentae are the main source of circulating activin A. These results suggest that increased levels of activin A may be involved in folliculogenesis in the ovary during the second half of pregnancy in the golden hamster.
Assuntos
Ativinas/fisiologia , Subunidades beta de Inibinas/fisiologia , Folículo Ovariano/fisiologia , Placenta/metabolismo , Prenhez/fisiologia , Útero/metabolismo , Ativinas/biossíntese , Ativinas/sangue , Análise de Variância , Animais , Cricetinae , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Hormônio Foliculoestimulante/sangue , Idade Gestacional , Histerectomia , Subunidades beta de Inibinas/biossíntese , Subunidades beta de Inibinas/sangue , Inibinas/biossíntese , Inibinas/sangue , Mesocricetus , Ovariectomia , Placenta/cirurgia , GravidezRESUMO
BACKGROUND: Although interleukin (IL)-4 and IL-5 have been demonstrated to play a critical role in the pathophysiology of allergic diseases such as allergic rhinitis, the mechanism that causes the predominance of Th2 lymphocytes has yet to be clarified. Thymus and activation-regulated chemokine (TARC) has been known to facilitate the recruitment, activation and development of Th2 polarized cells, leading investigators to suggest a role for TARC in the development of Th2 responses. OBJECTIVE: To gain a better understanding of the role of TARC in the pathogenesis of allergic rhinitis we investigated the cellular sources of this chemokine in nasal mucosa. In addition, the effect of cytokines on TARC production has been investigated. METHODS: The expression of TARC in human nasal mucosa was assessed by immunohistochemistry. To study the effect of cytokines on TARC production, epithelial cells, endothelial cells and fibroblasts, isolated from inferior nasal mucosa samples, were stimulated by a variety of cytokines including IL-4, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma. RESULTS: Epithelial cells in nasal mucosa in subjects with allergic rhinitis expressed higher signal level than those in non-allergy patients. Combined stimulation with IL-4 and TNF-alpha, as well as IL-13 and TNF-alpha, synergistically induced TARC expression in epithelial cells. Furthermore, the amount of TARC induced by these cytokines was higher in epithelial cells obtained from patients with allergic rhinitis than in those from non-allergic patients. CONCLUSION: These results demonstrate a crucial role of nasal epithelial cells in the expression of TARC, and that Th2 cytokine IL-4 and IL-13 may promote Th2 responses by inducing TARC production from epithelial cells.
Assuntos
Quimiocinas CC/biossíntese , Citocinas/farmacologia , Mucosa Nasal/citologia , Mucosa Nasal/metabolismo , Adolescente , Adulto , Quimiocina CCL17 , Quimiocinas CC/genética , Criança , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Mucosa Nasal/efeitos dos fármacos , RNA Mensageiro/metabolismo , Rinite Alérgica Perene/metabolismo , Fator de Necrose Tumoral alfa/administração & dosagem , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Mitochondria play a central role in many apoptotic reactions. Although mitochondrial apoptotic changes and caspase activation have been demonstrated in the apoptotic thymocytes, cell death signal through mitochondria in TCR-stimulated thymocytes has not been fully understood. In this study, we show that TCR stimulation induced disruption of mitochondrial transmembrane potential (Delta Psi(m)), the cytochrome c release from mitochondira, capase-3 activation, and the cell death of thymocytes. Bongkrekic acid, an inhibitor of Delta Psi(m) disruption, blocked the cytochrome c release from mitochondria and the following caspase-3-mediated cell death. Furthermore, a pro-apoptotic Bcl-2 family protein, Bax, but not Bad or Bid, was translocated from cytosol to mitochondria in TCR-stimulated thymocytes. This translocation and the following apoptotic changes were inhibited by SB203580, a p38 kinase inhibitor, in a specific manner. These results suggest that activated p38 kinase pathway by TCR stimulation induces translocation of Bax to mitochondria, causing Delta Psi(m) disruption, and the release of cytochrome c, which finally induces caspase-3-mediated apoptosis in thymocytes.
Assuntos
Apoptose , Mitocôndrias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Timo/imunologia , Animais , Ácido Bongcréquico/farmacologia , Caspase 3 , Caspases/metabolismo , Células Cultivadas , Grupo dos Citocromos c/metabolismo , Dexametasona/farmacologia , Sistema de Sinalização das MAP Quinases , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Transporte Proteico , Linfócitos T/imunologia , Proteína X Associada a bcl-2 , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Osmotic shock induced transient stabilization of p53, possibly due to increased degradation of Mdm2. Stabilized p53 was activated by p38(MAPK), resulting in G(1) arrest through induction of p21(WAF1). Among the postulated phosphorylation sites involved in p53 stabilization or activation (Ser(15), Ser(20), Ser(33), and Ser(46)), only Ser(33) was phosphorylated. Furthermore, interaction of p53 with the transcriptional coactivator p300 was induced, and Lys(382) of p53 was acetylated. Although inhibition of p38(MAPK) did not prevent nuclear accumulation of p53, phosphorylation of Ser(33) was markedly suppressed by SB203580, a specific inhibitor of p38(MAPK). Under these conditions, acetylation of Lys(382) and induction of p21(WAF1) were also inhibited, and cells with elevated levels of p53 showed normal cell cycle progression. Activated p38(MAPK) phosphorylated endogenous p53 at Ser(33) in living cells. In stable transformants expressing dominant negative MKK6, an upstream protein kinase of p38(MAPK), p53 stabilization was induced normally following osmotic shock, but phosphorylation of Ser(33), acetylation of Lys(382), and induction of p21(WAF1) were almost completely inhibited. These results suggest that phosphorylation at Ser(33) by p38(MAPK) is critical for activation of p53 following osmotic shock. Phosphorylation of neither Ser(15) nor Ser(20) was needed in this activation.
Assuntos
Fase G1 , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Pressão Osmótica , Fosforilação , Serina/química , Proteína Supressora de Tumor p53/metabolismo , Acetilação , Animais , Western Blotting , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Ciclo Celular , Linhagem Celular , Núcleo Celular/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/metabolismo , Regulação para Baixo , Proteína p300 Associada a E1A , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Fibroblastos/metabolismo , Genes Dominantes , Genes p53 , Humanos , Imidazóis/farmacologia , Luciferases/metabolismo , Lisina/química , MAP Quinase Quinase 6 , Camundongos , Camundongos Knockout , Proteínas Nucleares , Plasmídeos/metabolismo , Testes de Precipitina , Ligação Proteica , Piridinas/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Transativadores , Transcrição Gênica , Ativação Transcricional , Transfecção , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
OBJECTIVE: The treatment for brain metastasis has undergone remarkable changes since the development of radiosurgery. We investigated the results of treatment for brain metastasis from lung cancer since the initiation of gamma knife radiosurgery (GKRS) and we discuss the usefulness of GKRS combined with other treatments in cases with recurrence. METHODS: We treated 142 patients with brain metastasis from lung cancer. Sixteen patients were treated surgically, 11 patients were treated with whole brain radiation therapy (WBRT), and 115 patients were treated with GKRS. Our treatment plan is to use GKRS in cases with less than 5 lesions and lesions less than 3 cm in mean diameter. We use WBRT in cases with 5 or more lesions, and surgery in cases with lesions 3 cm or larger. If new lesions or tumor regrowth appeared after the initial treatment, we retreated them with one of the methods mentioned above. RESULTS: Twice or three-time treatments were performed in 30 patients. Median survival including all cases was 10 months and the number of deaths due to local treatment failure was only 5 (6.5%) out of the total 77 deaths which occurred. CONCLUSION: We were able to carry out less invasive treatment for brain metastasis from lung cancer by utilizing GKRS. Though we have to consider the indications for other treatments, we can say that radiosurgery is usually the treatment of first choice for brain metastasis from lung cancer. When new lesions appear in cases where a particular initial treatment was used, it is possible to maintain or improve the quality of life by retreatment, using a combination of GKRS, surgery or WBRT, to prolong the patient's life.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Neoplasias Pulmonares/patologia , Radiocirurgia , Adenocarcinoma/radioterapia , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/radioterapia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Irradiação Craniana , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Interleukin 6 (IL-6) plays important roles in the immune system, hematopoiesis, as well as the growth of various tumors. Androgens are important in the initiation and progression of prostate cancer and their effects are mediated by androgen receptor (AR). Here we present a molecular mechanism for the effects of IL-6 on prostate cancer cells through a cross-talk between IL-6 and AR signaling pathways. IL-6-induced activation of signal transducer and activator of transcription 3 (STAT3) was augmented by AR in the presence of dihydrotestosterone (DHT). In addition, DHT treatment augmented endogenous STAT3-mediated gene expression by IL-6. Conversely, DHT-induced AR activity was increased by IL-6, and a dominant negative form of STAT3 inhibited AR activation. In contrast, DHT-mediated enhancement of STAT3 activation was inhibited by flutamide, an AR antagonist. We provide evidence that these activities are due to direct physical interactions between STAT3 and AR in prostate cancer cells.
Assuntos
Carcinoma/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Transdução de Sinais/fisiologia , Transativadores/metabolismo , Antagonistas de Receptores de Andrógenos , Antineoplásicos Hormonais/farmacologia , Carcinoma/tratamento farmacológico , Proteínas de Ligação a DNA/genética , Di-Hidrotestosterona/farmacologia , Sinergismo Farmacológico , Flutamida/farmacologia , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/farmacologia , Neoplasias Renais/metabolismo , Masculino , Neoplasias da Próstata/tratamento farmacológico , Ligação Proteica/efeitos dos fármacos , Fator de Transcrição STAT3 , Transdução de Sinais/efeitos dos fármacos , Transativadores/genética , Ativação Transcricional/efeitos dos fármacos , Transfecção , Células Tumorais CultivadasRESUMO
To investigate the roles of various hematopoietic cell-specific adapter proteins in T cell receptor (TCR)-signaling leading to nuclear factor of activated T cell (NF-AT) and nuclear factor of kappaB (NF-kappaB) activation, we reconstituted TCR-signaling with CD8/zeta, various protein tyrosine kinases (PTKs), and adapter proteins in a non-lymphoid cell line, 293T. We show that SLP-76 and BLNK, but not LAT, effectively co-operated with Syk and Tec family PTKs to activate NF-AT and NF-kappaB. We also show that Tec family PTKs enhanced endogenous phospholipase C (PLC)-gamma1 phosphorylation induced by CD8/zeta and Syk in 293T cells. These results imply that PLC-gamma1 may play a critical role in a hematopoietic cell-specific adapter protein-mediated NF-AT and NF-kappaB activation in a non-lymphoid cell.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte/metabolismo , Proteínas de Ligação a DNA/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Proteínas de Membrana , NF-kappa B/metabolismo , Proteínas Nucleares , Fosfoproteínas/metabolismo , Fatores de Transcrição/metabolismo , Tirosina Quinase da Agamaglobulinemia , Animais , Antígenos CD8/genética , Antígenos CD8/metabolismo , Proteínas de Transporte/genética , Linhagem Celular , Precursores Enzimáticos/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Isoenzimas/metabolismo , Fatores de Transcrição NFATC , Fosfolipase C gama , Fosfoproteínas/genética , Fosforilação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Tirosina Quinases/metabolismo , Ratos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais/imunologia , Quinase Syk , Fosfolipases Tipo C/metabolismo , Tirosina/metabolismoRESUMO
Myosin light chain kinase (MLCK) is a regulatory protein for smooth muscle contraction, which acts by phosphorylating 20-kDa myosin light chain (MLC20) to activate the myosin ATPase activity. Although this mode of action is well-established, there are numerous reports of smooth muscle contraction that is not associated with MLC20 phosphorylation. The kinase activity for the phosphorylation is localized at the central part of MLCK, which is also furnished with actin-binding activity at its N terminal and myosin-binding activity at its C terminal. This article overviews as to how such multifunctional properties of MLCK modify the actin-myosin interaction and presents our observations that the phosphorylation is not obligatory in induction of smooth muscle contraction.
Assuntos
Contração Muscular , Músculo Liso/fisiologia , Quinase de Cadeia Leve de Miosina/fisiologia , Actinas/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Sítios de Ligação , Calmodulina/metabolismo , Catálise , Músculo Liso/enzimologia , Miofibrilas/metabolismo , Quinase de Cadeia Leve de Miosina/química , Quinase de Cadeia Leve de Miosina/genética , Estrutura Terciária de Proteína , Proteínas Recombinantes/metabolismoRESUMO
Dural arteriovenous fistulae (DAVF's) in the anterior cranial fossa are uncommon. We encountered three patients with DAVF's in the anterior cranial fossa and reviewed the pertinent literature with regard to the etiology. All patients are middle-aged males. Two of three patients had massive intracranial hemorrhage, subarachnoidal hemorrhage in one and subdural hemorrhage in the other. One patient had a ruptured middle cerebral artery aneurysm and DAVF at the anterior cranial fossa was detected only incidentally. Angiographically, blood supplies were from the bilateral enlarged anterior ethmoidal arteries. These drained into the superior sagittal sinus via dilated frontal cortical veins. In all the patients, coagulation of the fistulous connections was carried out and the postoperative courses were uneventful. Angiographies revealed complete disappearance of the DAVF's. In conclusion, compared to cases of DAVF's in the other locations, DAVF's of the anterior cranial fossa are more likely to be brought on by sudden massive intracranial hemorrhage, and should be treated, even if asymptomatic, at the time of diagnosis. Surgical obliteration of the fistulous connection is sufficient treatment for DAVF in the anterior cranial fossa. Literature review strongly suggests that DAVF's involving the anterior cranial fossa are acquired lesions.
Assuntos
Malformações Vasculares do Sistema Nervoso Central/etiologia , Idoso , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Hemorragia Cerebral/complicações , Craniotomia , Eletrocoagulação , Humanos , Masculino , Pessoa de Meia-Idade , Base do CrânioRESUMO
OBJECT: The purpose of this study is to show some limitations of 3D-CTA to diagnose cerebral aneurysms. METHODS: Sixteen saccular aneurysms less than 10 mm in diameter were included. Large and complicated aneurysms were excluded. RESULTS: Although information about perforating arteries from the posterior cerebral artery is very important for surgery of basilar bifurcation aneurysms, 3D-CTA could not delineate the perforating arteries. A small posterior communicating artery (Pcom.A.) was not detected, and it was very difficult to differentiate infundibular dilatation of the Pcom. A. from an aneurysm. A small aneurysm of the distal middle cerebral artery could not be detected. Flow direction can not be determined by 3D-CTA, and nor could the side of the neck of the anterior communicating artery aneurysm be determined. Fenestration of the anterior communicating artery and the origin of the triple anterior cerebral artery were both misdiagnosed as anterior communicating artery aneurysms. CONCLUSION: It is premature to consider 3D-CTA as a replacement for conventional angiography.