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3.
Ann Am Thorac Soc ; 11(1): 92-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24460439

RESUMO

Disorders of the pulmonary lymphatic system include macro- and microcystic lymphatic malformations, primary or secondary lymphangiectasias, generalized lymphatic anomalies, diffuse pulmonary lymphangiomatosis, and combinations of lymphatic and other tissue anomalies, including lymphangioleiomyomatosis (LAM). We report a case of a patient with a newly defined entity classified as kaposiform lymphangiomatosis (KLA). This 50-year-old nonsmoking Hispanic woman presented with a 20-year history of cough, hemoptysis, chyloptysis, and pleuritic chest pain. Laboratory evaluation demonstrated a low normal platelet count, elevated d-Dimer, low normal fibrinogen, and elevated fibrin split products. Chest computerized tomography imaging showed enlarged hypodense lymph nodes in the mediastinum and hila, and peribronchovascular thickening, without evidence of cystic parenchymal lesions. Magnetic resonance imaging of the chest showed cystic mediastinal lymph nodes with heterogeneously increased T2 and decreased T1 signal intensity. Fiberoptic bronchoscopy revealed hyperemic mucosa with granular appearance suggestive of a submucosal infiltrative process. Pathological specimens revealed dilated, malformed lymphatic channels within the pleura, pulmonary septa, and bronchovascular bundles, and foci of perilymphatic and intralymphatic spindle cells which reacted with the Prospero homeobox protein 1 (PROX-1) immunostain. The morphology and immunohistochemistry results were consistent with a diagnosis of KLA. This newly recognized clinical-pathological entity among intrathoracic lymphatic anomalies is distinguished from generalized lymphatic anomaly and diffuse pulmonary lymphangiomatosis in part by characteristic hematological abnormalities and hemorrhagic complications, including hemoptysis, as experienced by our patient.


Assuntos
Pneumopatias/congênito , Pulmão/patologia , Linfangiectasia/congênito , Malformações Vasculares/diagnóstico , Quilo , Tosse/etiologia , Feminino , Hemoptise/etiologia , Humanos , Pneumopatias/complicações , Pneumopatias/diagnóstico , Pneumopatias/patologia , Linfangiectasia/complicações , Linfangiectasia/diagnóstico , Linfangiectasia/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Malformações Vasculares/complicações , Malformações Vasculares/patologia
4.
Vasc Med ; 18(2): 92-4, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23493623

RESUMO

A 23-year-old male presented from a nursing home with hypotension, tachycardia, diaphoresis and electrocardiographic evidence of right ventricular strain that was confirmed by echocardiography. His differential diagnosis included sepsis and pulmonary embolism. A high-resolution computed tomography scan demonstrated no pulmonary emboli but did demonstrate multiple bilateral pulmonary nodules. Upon questioning he admitted to injecting a long-acting narcotic that had been manually macerated, dissolved in saline, and injected through an indwelling intravenous line. Lung biopsy findings were consistent with cellulose-induced perivascular granulomatosis. Cellulose granulomatosis can be seen in patients who inject medications designed for oral use and should be considered in patients who present with acute pulmonary hypertension.


Assuntos
Granuloma de Corpo Estranho/diagnóstico , Entorpecentes/efeitos adversos , Embolia Pulmonar/diagnóstico , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Doença Aguda , Celulose/análise , Diagnóstico Diferencial , Glucocorticoides/uso terapêutico , Granuloma de Corpo Estranho/diagnóstico por imagem , Granuloma de Corpo Estranho/tratamento farmacológico , Humanos , Injeções Intravenosas , Pneumopatias/diagnóstico por imagem , Pneumopatias/tratamento farmacológico , Pneumopatias/patologia , Masculino , Pacientes Ambulatoriais , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Sepse/diagnóstico , Sepse/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
5.
Arch Pathol Lab Med ; 136(6): 601-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22646265

RESUMO

CONTEXT: Differentiation of ductal adenocarcinoma of the pancreas from nonneoplastic pancreatic tissues can be challenging, especially in small biopsy and fine-needle aspiration specimens. OBJECTIVE: To investigate the utility of 26 immunohistochemical markers (CAM 5.2, CK [cytokeratin] 7, CK20, CK17, CK19, MUC1, MUC2, MUC4, MUC5AC, MUC6, p53, DPC4/SMAD4, CDX2, pVHL [von Hippel-Lindau tumor suppressor gene protein], S100P, IMP-3 [insulin-like growth factor 2 messenger RNA binding protein 3], maspin, mesothelin, claudin 4, claudin 18, annexin A8, fascin, PSCA [prostate stem cell antigen], MOC31, CEA [carcinoembryonic antigen], and CA19-9 [cancer antigen 19-9]) in the diagnosis of ductal adenocarcinoma of the pancreas. DESIGN: Immunohistochemical staining for these markers was performed in 60 cases of pancreatic ductal adenocarcinoma on routine and tissue microarray sections. In addition, immunohistochemical staining for maspin, S100P, IMP-3, and pVHL was performed on cell blocks from 67 pancreatic fine-needle aspiration cases, including 44 cases of pancreatic ductal adenocarcinoma. RESULTS: The results demonstrated that (1) more than 90% of cases of ductal adenocarcinoma were positive for maspin, S100P, and IMP-3; (2) nearly all adenocarcinoma cases were negative for pVHL, whereas nonneoplastic ducts and acini were positive for pVHL in all cases; (3) normal/reactive pancreatic ducts were frequently positive for CK7, CK19, MUC1, MUC6, CA19-9, MOC31, PSCA, mesothelin, annexin A8, claudin 4, and claudin 18; (4) normal pancreatic ducts were usually negative for IMP-3, maspin, S100P, CK17, MUC2, MUC4, and MUC5AC; (5) 60% of adenocarcinomas were negative for DPC4/SMAD4; and (6) strong background staining was frequently seen with fascin, PSCA, and annexin A8. CONCLUSIONS: pVHL, maspin, S100P, and IMP-3 constitute the best diagnostic panel of immunomarkers for confirming the diagnosis of pancreatic ductal adenocarcinoma in both surgical and fine-needle aspiration specimens.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Imuno-Histoquímica/métodos , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Biópsia por Agulha Fina , Carcinoma Ductal Pancreático/metabolismo , Humanos , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo
6.
Invest Ophthalmol Vis Sci ; 47(9): 4011-8, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16936117

RESUMO

PURPOSE: To investigate histamine-induced changes in the phosphorylation of myosin light chain (MLC) and its influence on the barrier integrity of corneal endothelial cells through altered contractility of the actin cytoskeleton. METHODS: Experiments were performed in cultured bovine corneal endothelial cells (BCECs). Phosphorylation of MLC, which increases contractility of the actin cytoskeleton through actomyosin interaction, was assessed by urea-glycerol gel electrophoresis and Western blot analysis. Immunocytochemistry was used to locate phosphorylated MLC in relation to tight junctions. Phosphorylation of the 17-kDa PKC-potentiated inhibitory protein of type 1 protein phosphatase (CPI-17), which inhibits MLC phosphatase, was studied using Western blot analysis. The cortical actin cytoskeleton was visualized by staining with Texas-red phalloidin. Barrier integrity was determined by quantifying horseradish peroxidase (HRP; 44 kDa) flux across cells grown on porous filters. RESULTS: RT-PCR and Western blot analysis confirmed the expression of Galphaq/11-coupled H1 receptors in BCECs. Exposure to histamine (100 microM; 10 minutes) led to phosphorylation of MLC (134% relative to untreated cells) and of CPI-17. Histamine also increased the flux of HRP by sevenfold and disrupted the assembly of the dense cortical actin found in resting cells. PKC activation by phorbol 12-myristate 13-acetate (PMA; 100 nM; 30 minutes) caused phosphorylation of both MLC and CPI-17. The histamine-induced MLC phosphorylation was reduced by pre-exposure to either ML-7 (50 microM), an MLCK (MLC kinase) inhibitor, or chelerythrine (10 microM), an inhibitor of PKC. Cotreatment with agents that elevate cAMP in BCECs prevented the histamine-induced MLC phosphorylation and the disruption of the actin cytoskeleton, and increased HRP flux. Phosphorylated MLC in response to histamine or PMA was found in a punctate form in close proximity to ZO-1, a marker of the tight junctional complex. CONCLUSIONS: Histamine induces MLC phosphorylation by activating MLCK and partly inhibiting MLC phosphatase. The latter is facilitated by the phosphorylation of CPI-17. Localization of phosphorylated MLC in proximity to ZO-1 suggests increased contractility of the cortical actin at the tight junctional complex. This contractility oppose the tethering forces and lead to a breakdown of the barrier integrity. Last, elevated cAMP prevents histamine-induced loss of the barrier integrity, not only by blocking inactivation of MLC phosphatase but also by inactivating MLCK.


Assuntos
Endotélio Corneano/metabolismo , Histamina/farmacologia , Cadeias Leves de Miosina/metabolismo , Miosina Tipo II/metabolismo , Junções Íntimas/metabolismo , Actinas/metabolismo , Animais , Western Blotting , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Bovinos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Cultivadas , AMP Cíclico/metabolismo , Eletroforese em Gel de Poliacrilamida , Microscopia de Fluorescência , Quinase de Cadeia Leve de Miosina/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Proteína Quinase C/metabolismo , Receptores Histamínicos H1/genética , Receptores Histamínicos H1/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Acetato de Tetradecanoilforbol/farmacologia
7.
Cardiovasc Pathol ; 11(4): 244-7, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12140131

RESUMO

We describe an unusual case of a body cavity-based lymphoma, otherwise termed primary effusion lymphoma (PEL), involving the atria of the heart of an HIV-seropositive patient. This is the first reported case of the involvement of the heart by this rare lymphoma. This HIV-related lymphoma represents a distinct B-cell malignancy associated with human herpesvirus-8 (HHV-8) infection. It is characterized by involvement of body cavities, with infrequent evidence of organ or bone marrow infiltration. The tumor cells are large, nucleolated with an immunoblastic or anaplastic appearance, positive for activation markers, such as CD30, and negative for B-cell and T-cell immunophenotypic markers. Integration of HHV-8 DNA sequences is considered the hallmark of PEL. The tumor demonstrates frequent association with Epstein-Barr virus (EBV) and uniform absence of c-myc oncogene rearrangement, unlike most other HIV-related lymphomas.


Assuntos
Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/virologia , Herpesvirus Humano 8/isolamento & purificação , Linfoma/patologia , Linfoma/virologia , Adulto , DNA de Neoplasias/genética , DNA Viral/genética , Soropositividade para HIV/complicações , Átrios do Coração/patologia , Neoplasias Cardíacas/complicações , Herpesvirus Humano 8/genética , Humanos , Linfoma/complicações , Masculino , Derrame Pericárdico/complicações
8.
Biochim Biophys Acta ; 1574(2): 117-30, 2002 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-11955620

RESUMO

We previously reported on the isolation of a new rat ATP binding cassette (ABC) transporter, ABCB6. We now report the isolation of the full-length cDNA and genomic clones containing the human ABCB6 gene. ABCB6 is 100% identical to the cloned MTABC3 human ABC transporter and contains the typical ABC signature, Walker A and B motifs. We found that HuABCB6 is expressed at low levels in normal human liver. We found that ABCB6 was overexpressed in human hepatocellular carcinomas compared to paired surrounding non-malignant tissue. We found that there was no difference in ABCB6 gene copy between human liver cancer and its paired non-malignant tissue. Because HuABCB6 was overexpressed in human cancers compared to peri-tumoral tissue in the absence of gene amplification, transcriptional regulation may play an important role in its expression. Therefore, we isolated a 14 kb genomic DNA clone containing the HuABCB6 promoter and 5'-flanking region. The 5'-flanking region contains a CpG island, lacks an appropriately positioned TATA element and contains a number of putative transcription factor binding sites. Two transcription start sites were identified by S1 nuclease mapping at -274 and -296 bp from the start codon. Transient transfection of the HuABCB6 promoter constructs (HuABCB6/1.68, 1.39, 1.13, 0.90, 0.52) containing the luciferase reporter gene resulted in a 1100-2300-fold increase in luciferase activity compared to the empty vector control whereas HuABCB6/1.68 subcloned in the reverse orientation resulted in no activity. We observed a significant decrease in luciferase activity with the promoter constructs, HuABCB6/0.25, 0.15 and 0.06, which indicates that an orientation-dependent functional promoter is contained within our previously predicted promoter region of -315 bp to -565 bp as deletion of this 250 bp sequence resulted in a loss of promoter activity.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/biossíntese , Transportadores de Cassetes de Ligação de ATP/química , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Clonagem Molecular , DNA Complementar/biossíntese , DNA Complementar/química , Humanos , Fígado/metabolismo , Dados de Sequência Molecular , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Endonucleases Específicas para DNA e RNA de Cadeia Simples , Transfecção , Células Tumorais Cultivadas
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