RESUMO
Polyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models. Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice. Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of chronic obstructive pulmonary disease (COPD) patients. These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways. Poly I:C induced increased numbers of neutrophils and natural killer cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively. Using gene set variation analysis on representative clinical data sets, gene sets defined by poly I:C-induced differentially expressed genes were enriched in the molecular profiles of COPD but not idiopathic pulmonary fibrosis patients. Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.
Assuntos
Poli I-C/imunologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia , Viroses/genética , Viroses/imunologia , Animais , Movimento Celular , Modelos Animais de Doenças , Estudos de Viabilidade , Redes Reguladoras de Genes/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Células Matadoras Naturais/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , RNA de Cadeia Dupla/imunologia , Receptores CCR5/metabolismo , Receptores de Interleucina-8B/metabolismo , Transcriptoma/imunologiaRESUMO
Elevated levels of plasma homocysteine (Hcy) called hyperhomocysteinemia (HHcy) have been implicated in inflammation and remodeling in intestinal vasculature, and HHcy is also known to aggravate the pathogenesis of inflammatory bowel disease (IBD). Interestingly, colon is the pivotal site that regulates Hcy levels in the plasma. We hypothesize that HHcy decreases intestinal motility through matrix metalloproteinase-9 (MMP-9)-induced intestinal remodeling leading to constipation. To verify this hypothesis, we used C57BL/6J or wild-type (WT), cystathionine ß-synthase (CBS(+/-)), MMP-9(-/-), and MMP-9(-/-) + Hcy mice. Intestinal motility was assessed by barium meal studies and daily feces output. Plasma Hcy levels were measured by HPLC. Expression of ICAM-1, inducible nitric oxide synthase, MMP-9, and tissue inhibitors of MMPs was studied by Western blot and immunohistochemistry. Reactive oxygen species (ROS) including super oxide were measured by the Invitrogen molecular probe method. Tissue nitric oxide levels were assessed by a commercially available kit. Plasma Hcy levels in the treated MMP-9 group mice were comparable to CBS(+/-) mice. Barium meal studies suggest that intestinal motility is significantly decreased in CBS(+/-) mice compared with other groups. Fecal output-to-body weight ratio was significantly reduced in CBS(+/-) mice compared with other groups. There was significant upregulation of MMP-9, iNOS, and ICAM-1 expression in the colon from CBS(+/-) mice compared with WT mice. Levels of ROS, superoxide, and inducible nitric oxide were elevated in the CBS(+/-) mice compared with other groups. Results suggest that HHcy decreases intestinal motility due to MMP-9-induced intestinal remodeling leading to constipation.
Assuntos
Colo/fisiologia , Constipação Intestinal/etiologia , Motilidade Gastrointestinal/efeitos dos fármacos , Hiper-Homocisteinemia/fisiopatologia , Metaloproteinase 9 da Matriz/metabolismo , Animais , Cistationina beta-Sintase/genética , Fezes , Hiper-Homocisteinemia/complicações , Molécula 1 de Adesão Intercelular/biossíntese , Masculino , Metaloproteinase 9 da Matriz/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/biossíntese , Inibidor Tecidual de Metaloproteinase-1/biossínteseRESUMO
BACKGROUND: Image-directed biopsies may be collected as histologic or cytologic specimens. METHODS: In 34 patients, the results of aspiration cytologic examination were compared prospectively with core tissue biopsy findings obtained and diagnosed independently using the same image-guided procedure. RESULTS: Cytologic examination disclosed 22 patients with positive or suspicious findings of malignancy; there was one false-suspicious result. Seventeen patients with such results were discovered by examining the core biopsy specimens. Cytologic findings also were more definitive in diagnosing malignancy. Those in whom an immediate interpretation could be done were more likely to have adequate cytologic specimens (88%) than those without (62%). One to five passes were done, but all 21 patients with definitive findings of either benign or malignant by cytologic examination underwent three or fewer passes. The three patients with positive biopsy results, but less definitive cytologic findings, all underwent only one cytologic pass. CONCLUSIONS: Therefore, it was concluded that cytologic examination is more sensitive and definitive than biopsy in diagnosing lesions using image guidance. Immediate interpretation and/or multiple passes increase the diagnostic yield. However, more than three aspiration cytologic passes appear to yield diminishing returns.
Assuntos
Biópsia por Agulha/métodos , Diagnóstico por Imagem , Neoplasias/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Estudos Prospectivos , Sensibilidade e EspecificidadeAssuntos
Doenças da Hipófise/cirurgia , Sela Túrcica/cirurgia , Tuberculoma/cirurgia , Tuberculose Meníngea/cirurgia , Adulto , Humanos , Masculino , Doenças da Hipófise/patologia , Hipófise/patologia , Pneumoencefalografia , Sela Túrcica/patologia , Tomografia Computadorizada por Raios X , Tuberculoma/patologia , Tuberculose Meníngea/patologiaRESUMO
A case of traumatic pseudo-aneurysm of the superficial temporal artery documented on Computed tomography (CT) and angiography is described in a 55-years-old female, who was treated by surgical excision. Computed tomographic appearance of this lesion is illustrated. This represents, to our knowledge, the first CT demonstration of traumatic aneurysm of superficial temporal artery within a large subgaleal haematoma.
Assuntos
Aneurisma/diagnóstico por imagem , Artérias Temporais/lesões , Tomografia Computadorizada por Raios X , Acidentes de Trabalho , Agricultura , Aneurisma/etiologia , Aneurisma/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/cirurgiaRESUMO
Magnetic resonance (MR) imaging of the spine was performed as the initial imaging technique in 20 children when spinal dysraphism was suspected clinically and plain radiographs showed spina bifida. The correlation with surgical findings indicated that MR provided accurate information preoperatively in all the cases. Some unusual observations in cases with spina bifida cystica and occulta are discussed. It is concluded that plain radiograph and MR complete the preoperative radiologic evaluation of cases with spinal dysraphism.
Assuntos
Imageamento por Ressonância Magnética , Medula Espinal/patologia , Disrafismo Espinal/diagnóstico , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Lipoma/diagnóstico , Defeitos do Tubo Neural/diagnóstico , Espinha Bífida Oculta/diagnóstico , Neoplasias da Medula Espinal/diagnóstico , Siringomielia/diagnósticoRESUMO
Malignant mesothelioma of the tunica vaginalis is rare, but sometimes curable. It is similar to malignant mesothelioma of the peritoneum and of the pleura, and is likewise associated with asbestos exposure. We report a case, with correlative computed tomography, ultrasound, and gross pathology images that demonstrate tiny tumor implants studding the vaginalis testis. The literature is reviewed.
Assuntos
Mesotelioma/diagnóstico , Neoplasias Testiculares/diagnóstico , Idoso , Amianto/efeitos adversos , Exposição Ambiental , Humanos , Masculino , Mesotelioma/diagnóstico por imagem , Mesotelioma/etiologia , Escroto/patologia , Membrana Serosa/patologia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/etiologia , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
A prospective study of lymph vessel abnormalities in the lower limbs of 744 adult patients without lymphoedema revealed seven patients with lymphatic hypoplasia, a prevalence rate of 0.94% (95% limits of confidence 0.24-1.64%). The prevalence was higher in males (1.1%) than in females (0.5%) but the difference is not statistically significant. This is much higher than any available estimate of the prevalence of primary lymphoedema of the lower limbs and suggests that lymphatic hypoplasia is merely one factor in the aetiology of clinical lymphoedema.