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1.
Clin Oncol (R Coll Radiol) ; 35(7): 429-445, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37061456

RESUMO

Cervical lymph node metastases from head and neck squamous cell cancers significantly reduce disease-free survival and worsen overall prognosis and, hence, deserve more aggressive management and follow-up. As per the eighth edition of the American Joint Committee on Cancer staging manual, extranodal extension, especially in human papillomavirus-negative cancers, has been incorporated in staging as it is important in deciding management and significantly impacts the outcome of head and neck squamous cell cancer. Lymph node imaging with various radiological modalities, including ultrasound, computed tomography and magnetic resonance imaging, has been widely used, not only to demonstrate nodal involvement but also for guided histopathological evaluation and therapeutic intervention. Computed tomography and magnetic resonance imaging, together with positron emission tomography, are used widely for the follow-up of treated patients. Finally, there is an emerging role for artificial intelligence in neck node imaging that has shown promising results, increasing the accuracy of detection of nodal involvement, especially normal-appearing nodes. The aim of this review is to provide a comprehensive overview of the diagnosis and management of involved neck nodes with a focus on sentinel node anatomy, pathogenesis, imaging correlates (including radiogenomics and artificial intelligence) and the role of image-guided interventions.


Assuntos
Inteligência Artificial , Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Prognóstico , Tomografia Computadorizada por Raios X , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Estadiamento de Neoplasias
3.
Free Radic Biol Med ; 145: 8-19, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31521664

RESUMO

The incidence of symptomatic radiation induced lung pneumonitis (RILP), a major dose limiting side effect of thoracic radiotherapy, is in the range of 15-40%. Therapeutic options for the prevention and treatment of RILP are limited. Hence there is a need for developing novel radioprotectors to prevent RILP which can be patient compliant. This study sought to evaluate the efficacy of oral 3,3'-diselenodipropionic acid (DSePA), a novel selenocystine derivative to prevent RILP. C3H/HeJ (pneumonitis responding) mice received a single dose of 18 Gy, whole thorax irradiation and a subset were treated with DSePA orally (2.5 mg/kg), three times per week beginning 2 h post irradiation and continued till 6 months. DSePA delayed onset of grade ≥ 2 RILP by 45 days compared to radiation control (~105 versus ~60 days). It also reversed the severity of pneumonitis in 3/10 radiation treated mice leading to significant improvement in asymptomatic survival compared to radiation control (~180 versus ~102 days). DSePA significantly (p < 0.05) reduced the radiation-mediated infiltration of polymorphonuclear neutrophils (PMN) and elevation in levels of cytokines such as IL1-ß, ICAM-1, E-selectin, IL-17 and TGF-ß in the bronchoalveolar lavage fluid. Moreover DSePA lowered PMN-induced oxidants, maintained glutathione peroxidase activity and suppressed NF-kB/IL-17/G-CSF/neutrophil axis in the lung of irradiated mice. Additionally, this compound did not protect A549 (lung cancer) derived xenograft tumor from radiation exposure in SCID mice. DSePA offers protection to normal lung against RILP without affecting radiation sensitivity of tumors. It has the potential to be developed as an oral agent for preventing RILP.


Assuntos
Fator Estimulador de Colônias de Granulócitos/genética , Interleucina-17/genética , Pneumonia/tratamento farmacológico , Propionatos/farmacologia , Lesões por Radiação/tratamento farmacológico , Compostos de Selênio/farmacologia , Células A549 , Administração Oral , Animais , Cistina/análogos & derivados , Cistina/genética , Modelos Animais de Doenças , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/efeitos da radiação , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/prevenção & controle , Camundongos , NF-kappa B/genética , Neutrófilos/metabolismo , Neutrófilos/efeitos da radiação , Compostos Organosselênicos , Pneumonia/diagnóstico por imagem , Pneumonia/etiologia , Pneumonia/genética , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/genética , Lesões por Radiação/patologia , Transdução de Sinais/efeitos da radiação
4.
Am J Physiol Lung Cell Mol Physiol ; 317(1): L49-L56, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30969811

RESUMO

Bronchopulmonary dysplasia (BPD) remains a devastating consequence of prematurity. Repeated inflammatory insults worsen lung injury, but there are no predictors for BPD-related respiratory outcomes or targeted therapies. We sought to understand inflammatory mechanisms in evolving BPD through molecular characterization of monocytes in tracheal aspirates from infants at risk for developing BPD. We performed flow cytometry targeting myeloid cell populations on prospectively collected tracheal aspirates from intubated patients born before 29 wk of gestation and <30 days old. We identified CD14+CD16+ (double-positive) and CD14+CD16- (single-positive) monocytes and characterized their gene expression profiles by RNA sequencing and quantitative PCR. We further analyzed differential gene expression between time points to evaluate changes in monocyte function over the first weeks of life. Expression of IL-1A, IL-1B, and IL-1 receptor antagonist mRNA was increased in monocytes collected at day of life (DOL) 7, DOL 14, and DOL 28 compared with those collected at DOL 3. This study suggests that early changes in monocyte-specific IL-1 cytokine pathways may be associated with evolving BPD.


Assuntos
Displasia Broncopulmonar/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1alfa/genética , Interleucina-1beta/genética , Monócitos/imunologia , RNA Mensageiro/genética , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Displasia Broncopulmonar/imunologia , Displasia Broncopulmonar/patologia , Feminino , Proteínas Ligadas por GPI/deficiência , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Regulação da Expressão Gênica , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Interleucina-1alfa/imunologia , Interleucina-1beta/imunologia , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/imunologia , Masculino , Monócitos/patologia , Projetos Piloto , Estudos Prospectivos , RNA Mensageiro/imunologia , Receptores de IgG/deficiência , Receptores de IgG/genética , Receptores de IgG/imunologia , Análise de Sequência de RNA , Transdução de Sinais , Traqueia/imunologia , Traqueia/patologia
5.
J Immunol ; 202(9): 2772-2781, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30944158

RESUMO

Inflammation in response to oxygen exposure is a major contributing factor in neonatal lung injury leading to bronchopulmonary dysplasia. Although increased levels of proinflammatory cytokines are seen in airway samples and blood from bronchopulmonary dysplasia patients, the innate immune responses in this common neonatal lung condition have not been well characterized. We previously reported that depletion of murine CD11b-expressing mononuclear phagocytes at birth led to severe acute hyperoxia-induced lung injury (HILI) and significant mortality. In this study, we further define the mononuclear phagocyte populations that are present in the neonatal lung and characterize their responses to hyperoxia exposure. We used myeloid depleter mice (CD11b-DTR and CCR2-DTR) to contrast the effects of depleting different monocyte/macrophage subpopulations on the innate immune response to hyperoxia. Using RNA sequencing and subsequent data analysis, we identified an IFN-γ-mediated role for interstitial monocytes/macrophages in acute HILI, in which decreased IFN-γ expression led to increased disease severity and increased Mmp9 mRNA expression. Importantly, intranasal administration of rIFN-γ largely rescued CD11b-DTR+ mice from severe HILI and decreased Mmp9 mRNA expression in Ly-6Clo and Ly-6Chi interstitial monocyte/macrophages. We conclude that the proinflammatory effects of hyperoxia exposure are, at least in part, because of the modulation of effectors downstream of IFN-γ by pulmonary monocytes/macrophages.


Assuntos
Antígenos Ly/imunologia , Hiperóxia/imunologia , Interferon gama/imunologia , Lesão Pulmonar/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Animais , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/imunologia , Hiperóxia/patologia , Interferon gama/farmacologia , Lesão Pulmonar/patologia , Macrófagos/patologia , Metaloproteinase 9 da Matriz/imunologia , Camundongos , Monócitos/patologia
6.
AJNR Am J Neuroradiol ; 39(6): 1008-1016, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29794239

RESUMO

BACKGROUND AND PURPOSE: Standard assessment criteria for brain tumors that only include anatomic imaging continue to be insufficient. While numerous studies have demonstrated the value of DSC-MR imaging perfusion metrics for this purpose, they have not been incorporated due to a lack of confidence in the consistency of DSC-MR imaging metrics across sites and platforms. This study addresses this limitation with a comparison of multisite/multiplatform analyses of shared DSC-MR imaging datasets of patients with brain tumors. MATERIALS AND METHODS: DSC-MR imaging data were collected after a preload and during a bolus injection of gadolinium contrast agent using a gradient recalled-echo-EPI sequence (TE/TR = 30/1200 ms; flip angle = 72°). Forty-nine low-grade (n = 13) and high-grade (n = 36) glioma datasets were uploaded to The Cancer Imaging Archive. Datasets included a predetermined arterial input function, enhancing tumor ROIs, and ROIs necessary to create normalized relative CBV and CBF maps. Seven sites computed 20 different perfusion metrics. Pair-wise agreement among sites was assessed with the Lin concordance correlation coefficient. Distinction of low- from high-grade tumors was evaluated with the Wilcoxon rank sum test followed by receiver operating characteristic analysis to identify the optimal thresholds based on sensitivity and specificity. RESULTS: For normalized relative CBV and normalized CBF, 93% and 94% of entries showed good or excellent cross-site agreement (0.8 ≤ Lin concordance correlation coefficient ≤ 1.0). All metrics could distinguish low- from high-grade tumors. Optimum thresholds were determined for pooled data (normalized relative CBV = 1.4, sensitivity/specificity = 90%:77%; normalized CBF = 1.58, sensitivity/specificity = 86%:77%). CONCLUSIONS: By means of DSC-MR imaging data obtained after a preload of contrast agent, substantial consistency resulted across sites for brain tumor perfusion metrics with a common threshold discoverable for distinguishing low- from high-grade tumors.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Conjuntos de Dados como Assunto/normas , Glioma/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/normas , Imageamento por Ressonância Magnética/normas , Adulto , Idoso , Algoritmos , Neoplasias Encefálicas/patologia , Feminino , Glioma/patologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Estados Unidos
7.
J Postgrad Med ; 60(4): 372-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25370544

RESUMO

BACKGROUND: Ethyl alcohol exerts both positive and negative effects on the cardiovascular system. Alcoholic cardiomyopathy, produced by direct or indirect mechanisms, is well-documented. An important, but seldom appreciated effect is an increase in iron deposition in the myocardium, which can add to the cardiac dysfunction. The present study was planned to document the pathological features and iron levels in the cardiac tissue of patients who were chronic alcoholics and correlate these characteristics with the liver pathology and iron content. MATERIALS AND METHODS: An autopsy-based prospective study of 40 consecutive patients compared with ten age matched controls (no history of alcohol intake). Histopathological changes like the morphology of the cardiac myocytes, degree of fibrosis (interstitial, interfiber, perivascular, and replacement), presence of inflammatory cells, increased capillary network, and adipose tissue deposition were noted and graded. These were also correlated with the liver pathology. The iron content in the heart and liver were measured by using calorimetry. RESULTS: All cases had increased epicardial adipose tissue with epicardial and endocardial fibrosis, prominence of interstitial and interfiber fibrosis, myofiber degeneration, and increased capillary network; this was particularly prominent in patients with cirrhosis. Elemental iron level in heart tissue was raised in the cases relative to controls. CONCLUSIONS: Alcohol produces subclinical changes in the myocardium, with an increased iron content, which may be the forerunner for subsequent clinical cardiac dysfunction.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoólicos , Sobrecarga de Ferro/fisiopatologia , Hepatopatias/fisiopatologia , Fígado/patologia , Miocárdio/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/metabolismo , Autopsia , Feminino , Humanos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/metabolismo , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
8.
J Perinatol ; 34(8): 645-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25073497

RESUMO

We describe a monozygotic twin discordant for VATER association with single dysplastic kidney and cloacal anomaly, who had no pulmonary hypoplasia. This twin probably had little or no urine output in utero, but still had normal lung development due to production of adequate amniotic fluid by the healthy twin preventing pulmonary hypoplasia. The discordance between monozygotic twins for VATER association indicates that factors other than inherited genetic ones may have a role in the causation of this association.


Assuntos
Anus Imperfurado/diagnóstico , Anus Imperfurado/terapia , Doenças em Gêmeos , Esôfago/anormalidades , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/terapia , Rádio (Anatomia)/anormalidades , Coluna Vertebral/anormalidades , Traqueia/anormalidades , Gêmeos Monozigóticos , Feminino , Humanos , Recém-Nascido
9.
Br J Neurosurg ; 27(3): 390-2, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23171146

RESUMO

Intracranial epidermoid cysts are uncommon lesions with typical radiological and operative findings. We report a midline cystic lesion in the pre-pontine cistern, with radiological features of an epidermoid, but intra-operatively yielding a thin-walled cyst with fluid contents. The cyst wall showed stratified squamous epithelium on histopathology.


Assuntos
Doenças Cerebelares/patologia , Cisto Epidérmico/patologia , Doenças Cerebelares/cirurgia , Ângulo Cerebelopontino/patologia , Pré-Escolar , Cisto Epidérmico/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Bulbo/patologia , Ponte/patologia
10.
J Nanosci Nanotechnol ; 12(5): 3788-98, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22852308

RESUMO

We herein report an economical and facile technique for the synthesis of hierarchical nanostructures of Cu doped CdS nanostructures by microwave assisted solvothermal technique using a household microwave oven. We attempted to establish the effect of variation of solvents ratio on the morphological and optical properties of the obtained nanoscale structures. The field emission characteristics of the copper doped CdS nanoarchitecture have been studied and the turn on field is found to be 2.8 V/microm for an emission current density of approximately 0.1 microA/cm2. Emission current stability is determined at the preset current of approximately 1 microA and approximately 10 microA for the stable duration of approximately 4 hrs. The observed field emission results envisage the possibility of using the present emitter in the field emission sources. We believe that this is a unique report on the synthesis as well as field emission studies of copper doped CdS nanostructures. Photocatalytic dye degradation ability of the Cu doped CdS nanostructures is observed to be less than the undoped CdS counterparts.

11.
Transplant Proc ; 44(3): 713-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22483475

RESUMO

Viral infections in renal allograft recipients constitute an important cause of renal graft dysfunction. They have shown an increasing incidence coinciding with more potent immunosuppression regimens. Cytomegalovirus (CMV) is well-known cause of a tubulointerstitial nephritis rich in plasma cells with cytopathic changes in tubular epithelial and endothelial cells. However, involvement of glomeruli and larger arteries in the absence of tubulointerstitial disease is rare. In this study, we demonstrated the spectrum of renal disease caused by CMV among renal allograft recipients. Retrospective analysis of 2900 renal allograft biopsies performed over a 10-year period revealed 10 cases of CMV infection, with half of them (5/10) detected in 2010-2011. Although tubulointerstitial nephritis due to CMV was the most common lesion (7/10), we noted an increased incidence of CMV glomerulopathy with (1/10) or without (3/10) coexisting tubulointerstitial CMV disease. Isolated glomerular involvement was characterized by a relative lack of inflammation in any of the compartments along with the presence of cytopathic changes in the glomerular endothelial cells and podocytes. Another patient had CMV-induced thrombotic microangiopathy. The coexistent diseases were calcineurin inhibitor toxicity (n = 1), antibody-mediated rejection (n = 1), cellular rejection (n = 2), and invasive fungal infection (n = 1). In conclusion, there is a wide spectrum of CMV-induced lesions. CMV glomerulopathy is characterized by cytopathic changes in glomerular endothelial cells and podocytes with a lack of significant inflammation. In contrast, CMV-induced arteriopathy can present as thrombotic microangiopathy. Coinfection with other pathogens like invasive fungi can lead to graft failure.


Assuntos
Citomegalovirus/patogenicidade , Nefropatias/virologia , Transplante de Rim , Adulto , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo
12.
J Photochem Photobiol B ; 91(1): 9-19, 2008 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-18316199

RESUMO

In photosynthetic organisms oxidative stress is known to result in photoinactivation of photosynthetic machinery. We investigated effects of (60)Co gamma radiation, which generates oxidative stress, on thylakoid structure and function in cyanobacteria. Cells of unicellular, non-nitrogen fixing cyanobacterium Anacystis nidulans (Synechococcus sp.) showed D(10) value of 257 Gy of (60)Co gamma radiation. When measured immediately after exposure, cells irradiated with 1500 Gy (lethal dose) of (60)Co gamma radiation did not show any differences in photosynthetic functions such as CO(2) fixation, O(2) evolution and partial reactions of photosynthetic electron transport in comparison to unirradiated cells. Incubation of irradiated cells for 24h in light or dark resulted in decline in photosynthesis. The decline in photosynthesis was higher in the cells incubated in light as compared to the cells incubated in dark. Among the partial reactions of electron transport, only PSII activity declined drastically after incubation of irradiated samples. This was also supported by the analysis of membrane functions using thermoluminescence. Exposure of cyanobacteria to high doses of (60)Co gamma radiation did not affect the thylakoid membrane ultrastructure immediately after exposure as shown by electron microscopy. The level of reactive oxygen species (ROS) in irradiated cells was 20 times higher as compared to control. In irradiated cells de novo protein synthesis was reduced considerably immediately after irradiation. Treatment of cells with tetracycline also affected photosynthesis as in irradiated cells. The results showed that photoinhibition of photosynthetic apparatus after incubation of irradiated cells was probably augmented due to reduced protein synthesis. Active photosynthesis is known to require uninterrupted replenishment of some of the proteins involved in electron transport chain. The defective thylakoid membrane biogenesis may be leading to photosynthetic decline post-irradiation.


Assuntos
Raios gama , Fotossíntese/efeitos da radiação , Synechococcus/efeitos da radiação , Tilacoides/efeitos da radiação , Dióxido de Carbono/metabolismo , Clorofila/metabolismo , Radioisótopos de Cobalto , Peroxidação de Lipídeos , Medições Luminescentes , Metionina/metabolismo , Microscopia Eletrônica de Transmissão , Estresse Oxidativo , Complexo de Proteína do Fotossistema I/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Synechococcus/metabolismo , Synechococcus/ultraestrutura , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Tilacoides/metabolismo
13.
Oncogene ; 27(22): 3156-64, 2008 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-18071317

RESUMO

Inactivation of the retinoblastoma (RB) tumor suppressor pathway, via elevated cyclin-dependent kinase (CDK) activity, is observed in majority of human cancers. Since CDK deregulation is evident in most cancer cells, pharmacological CDK inhibition has become an attractive therapeutic strategy in oncology. We recently showed that an oncogenic CDK4(R24C) mutation alters the subcellular localization of the normally nuclear RB phosphoprotein. Here, using 71 human cancer cell lines and over 300 primary human cancer tissues, we investigated whether changes in RB subcellular localization occur during human cancer progression. We uncover that diverse human cancers and their derived cell lines, particularly those with poor tumor differentiation, display significant cytoplasmic mislocalization of ordinarily nuclear RB. The nucleocytoplasmically distributed RB was derived via CDK-dependent and Exportin1-mediated nuclear export. Indeed, cytoplasmically mislocalized RB could be efficiently confined to the nucleus by pharmacologically reducing CDK activity or by inhibiting the Exportin1-mediated nuclear export pathway. Our observations uncover a post-translational CDK-dependent mechanism of RB inactivation and suggest that cytoplasmically localized RB may harbor a tumor promoting function. We propose that RB inactivation, via aberrant nucleocytoplasmic transport, may disrupt normal cell differentiation programs and accelerate the cancer process. These results are evidence that tumor cells modulate the protein transport machinery thereby making the protein transport process a viable therapeutic target.


Assuntos
Diferenciação Celular , Núcleo Celular/metabolismo , Neoplasias/metabolismo , Proteína do Retinoblastoma/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Células Cultivadas , Quinases Ciclina-Dependentes/metabolismo , Progressão da Doença , Células HCT116 , Células HT29 , Humanos , Carioferinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteína do Retinoblastoma/fisiologia , Transplante Heterólogo , Proteína Exportina 1
14.
Oncogene ; 27(17): 2507-12, 2008 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-17952112

RESUMO

The ability of transforming growth factor-beta (TGF-beta) to modulate various effects on distinct cell lineages has been a central feature of its multi-faceted nature. The purpose of this study was to access the effects of deletion of a key TGF-beta signal transducer, Smad3, on MAPK activation and v-Ras(Ha)-transformation of primary mouse embryonic fibroblasts (MEFs). We observe reduced TGF-beta1 and v-ras(Ha) mediated activation of the JNK and ERK MAPK pathway upon ablation of Smad3. Further, Smad3-deficient MEFs demonstrate resistance to v-ras(Ha)-induced transformation while the absence of Smad3 results in increased inhibition of farnesyl transferase activity. Taken together, these observations demonstrate that the absence of Smad3 protects fibroblasts from oncogenic transformation by (i) augmenting farnesyl transferase inhibition and (ii) suppressing the Ras-JNK MAPK pathway. These results provide new insights into the molecular mechanisms involved in v-Ras(Ha) oncogene-induced mesenchymal phenotypic transformation.


Assuntos
Alquil e Aril Transferases/metabolismo , Sistema de Sinalização das MAP Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteína Oncogênica p21(ras)/metabolismo , Proteína Smad3/metabolismo , Transgenes/genética , Animais , Linhagem Celular Transformada , Transformação Celular Neoplásica , Células Cultivadas , Chlorocebus aethiops , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Proteína Oncogênica p21(ras)/genética , Fenótipo , Proteína Smad3/deficiência , Proteína Smad3/genética , Fator de Crescimento Transformador beta/farmacologia
15.
Oncogene ; 26(47): 6724-37, 2007 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-17934481

RESUMO

Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Proper culmination of these diverse pathways forms the basis for an orderly generation of different cell types. Recent studies conducted over the past 10-15 years have revealed that hematopoietic cytokine receptor signaling is largely mediated by a family of tyrosine kinases termed Janus kinases (JAKs) and their downstream transcription factors termed STATs (signal transducers and activators of transcription). Aberration in these pathways, such as that caused by the recently identified JAK2V617F mutation, is an underlying cause for diseases such as leukemias and other myeloproliferative disorders. This recent discovery, when coupled with the fact that STATs are activated by oncoproteins such as BCR-ABL, underscores the importance of the JAK-STAT pathway in both normal cellular development and disease states.


Assuntos
Citocinas/metabolismo , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Receptores de Citocinas/fisiologia , Transdução de Sinais/fisiologia , Animais , Citocinas/fisiologia , Células-Tronco Hematopoéticas/enzimologia , Células-Tronco Hematopoéticas/metabolismo , Humanos
16.
Oncogene ; 25(17): 2489-99, 2006 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-16518416

RESUMO

We previously demonstrated that Jak3 is a primary response gene for G-CSF and ectopic overexpression of Jak3 can accelerate granulocytic differentiation of normal mouse bone marrow cells induced by G-CSF and GM-CSF. To gain insight into the regulation of G-CSF-induced transcription of Jak3, we constructed deletion and linker scanning mutants of the Jak3 promoter sequences and performed luciferase reporter assays in the murine myeloid cell line 32Dcl3, with and without G-CSF stimulation. These experiments showed that mutation of a -67 to -85 element, which contained a putative Sp1 binding site, or mutation of a -44 to -53 GAS element resulted in a marked reduction of Jak3 promoter activity. Electrophoretic mobility shift assays revealed that Sp1 and Stat3 present in nuclear lysates of 32Dcl3 cells stimulated with G-CSF can bind to the -67 to -85 element and -44 to -53 GAS element, respectively. In addition, cotransfection of a constitutively active mutant of Stat3 along with a Jak3 promoter/luciferase reporter resulted in enhanced Jak3 promoter activity. Together, these results demonstrate that activation of Jak3 transcription during G-CSF- induced granulocytic differentiation is mediated by the combined action of Sp1 and Stat3, a mechanism also shown to be important in IL-6-induced monocytic differentiation.


Assuntos
Diferenciação Celular , Regulação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos/farmacologia , Granulócitos/citologia , Proteínas Tirosina Quinases/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição Sp1/metabolismo , Transcrição Gênica , Animais , Células Cultivadas , Ensaio de Desvio de Mobilidade Eletroforética , Janus Quinase 3 , Camundongos , Proteínas Tirosina Quinases/metabolismo , Regulação para Cima
17.
J Matern Fetal Neonatal Med ; 17(5): 315-22, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-16147844

RESUMO

OBJECTIVE: To examine the effect of pre-induction cervical length, parity, gestational age at induction, maternal age and body mass index (BMI) on the possibility of successful delivery in women undergoing induction of labor. METHODS: In 822 singleton pregnancies, induction of labor was carried out at 35 to 42(+6) weeks of gestation. The cervical length was measured by transvaginal sonography before induction. The effect of cervical length, parity, gestational age, maternal age and BMI on the interval between induction and vaginal delivery within 24 hours was investigated using Cox's proportional hazard model. The likelihood of vaginal delivery within 24 hours and risk for cesarean section overall and for failure to progress was investigated using logistic regression analysis. RESULTS: Successful vaginal delivery within 24 hours of induction occurred in 530 (64.5%) of the 822 women. Cesarean sections were performed in 161 (19.6%) cases, 70 for fetal distress and 91 for failure to progress. Cox's proportional hazard model indicated that significant prediction of the induction-to-delivery interval was provided by the pre-induction cervical length (HR=0.89, 95% CI 0.88-0.90, p<0.0001), parity (HR=2.39, 95% CI 1.98-2.88, p<0.0001), gestational age (HR=1.13, 95% CI 1.07-1.2, p=or<0.0001) and birth weight percentile (HR=0.995, 95% CI 0.99-0.995, p=0.001), but not by maternal age or BMI. Logistic regression analysis indicated that significant prediction of the likelihood of vaginal delivery within 24 hours was provided by pre-induction cervical length (OR=0.86, 95% CI 0.84-0.88, p<0.0001), parity (OR=3.59, 95% CI 2.47-5.22, p<0.0001) and gestational age (OR=1.19, 95% CI 1.07-1.32, p=or<0.0001) but not by BMI or maternal age. The risk of cesarean section overall was significantly associated with all the variables under consideration, i.e., pre-induction cervical length (OR=1.09, 95% CI 1.06-1.11, p<0.0001), parity (OR=0.25, 95% CI 0.17-0.38, p<0.0001), BMI (OR=1.85, 95% CI 1.24-2.74, p=0.0024), gestational age (OR=0.88, 95% CI 0.78-0.98, p=0.0215) and maternal age (OR=1.04, 95% CI 1.01-1.07, p=0.0192). The risk of cesarean section for failure to progress was also significantly associated with pre-induction cervical length (OR=1.11, 95% CI 1.07-1.14, p<0.0001), parity (OR=0.26, 95% CI 0.15-0.43, p<0.0001), gestational age (OR=0.83, 95% CI 0.73-0.96, p=0.0097) and BMI (OR=2.07, 95% CI 1.27-3.37, p=0.0036). CONCLUSION: In women undergoing induction of labor, pre-induction cervical length, parity, gestational age at induction, maternal age and BMI have a significant effect on the interval between induction and delivery within 24 hours, likelihood of vaginal delivery within 24 hours and the risk of cesarean section.


Assuntos
Colo do Útero/diagnóstico por imagem , Trabalho de Parto Induzido , Ultrassonografia Pré-Natal , Adolescente , Adulto , Índice de Massa Corporal , Cesárea/estatística & dados numéricos , Feminino , Idade Gestacional , Humanos , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Tempo
18.
Ultrasound Obstet Gynecol ; 25(4): 353-6, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15736212

RESUMO

OBJECTIVES: To predict when delivery will occur, within 48 h and 7 days of presentation and before 35 weeks' gestation in women presenting with threatened preterm labor. METHODS: Sonographic measurement of cervical length was carried out in 510 women with singleton pregnancies presenting with threatened preterm labor and intact membranes at 24 to 33 + 6 weeks of gestation. The measurement was not taken into account in the subsequent management of the pregnancies. The outcome measures were delivery within 48 h and 7 days of presentation and delivery before 35 weeks. RESULTS: The median gestation at presentation was 30 + 1 (range, 24 to 33 + 6) weeks and the median cervical length was 25 (range, 1-51) mm. Delivery within 48 h of presentation occurred in 21 (4.1%) cases, delivery within 7 days occurred in 43 (8.4%) and delivery before 35 weeks occurred in 76 (14.9%). Logistic regression analysis demonstrated that the only significant independent predictor of delivery within 48 h was cervical length (odds ratio (OR), 0.73; 95% CI, 0.65-0.81) and for delivery within 7 days the independent predictors were cervical length (OR, 0.69; 95% CI, 0.63-0.76) and vaginal bleeding (OR, 19.42; 95% CI, 3.87-97.4). In the subgroup of women who did not deliver within 7 days of presentation, the incidence of delivery before 35 weeks was 7.1% (33 of 467) and the only significant independent predictor of such delivery was cervical length (OR, 0.92; 95% CI, 0.88-0.96, P < 0.0001). There was no significant independent contribution to any of the outcome measures from ethnic group, maternal age, gestational age, body mass index, parity, cigarette smoking or use of tocolytics. CONCLUSIONS: In women with threatened preterm labor sonographic measurement of cervical length helps to distinguish between true and false labor and to predict early preterm delivery.


Assuntos
Colo do Útero/diagnóstico por imagem , Membranas Extraembrionárias/diagnóstico por imagem , Trabalho de Parto Prematuro/diagnóstico por imagem , Adolescente , Adulto , Parto Obstétrico , Feminino , Idade Gestacional , Humanos , Trabalho de Parto Prematuro/complicações , Paridade , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Análise de Regressão , Sensibilidade e Especificidade , Fatores de Tempo , Ultrassonografia , Hemorragia Uterina/complicações , Hemorragia Uterina/diagnóstico por imagem
19.
Indian J Pathol Microbiol ; 48(1): 7-12, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16758774

RESUMO

Morphological evaluation of 140 bone marrow aspirations received in haematopathology laboratory with serologically established HIV infection, along with other relevant special haematological tests, was done during 1st Jan 1999 - 31st Dec 2002 at state government run tertiary care General Hospital in Maharashtra state, India. Out of 140 cases: 118 (84.28%) patients had anaemia, 25 (17.86%) had leukopenia, while 13 (9.28%) were thrombocytopenic. Dyserythropoiesis was present in 18 (12.86%) cases, dysmyelopoiesis 37 (26.43%) and micromegakaryocytes were noted in 44 (31.43%) cases. Haemophagocytosis was evident in 8 (5.71%) cases. Plasmacytosis encountered in 120 (85.71%) cases was a common feature. Based on clinical profile and results of other investigations 56 (40%) patients were clinically diagnosed to be of Mycobacterium tuberculosis (TB). Of these, 18 (12.86%) bone marrow aspirates were positive for AFB, Mycobacterium tuberculosis. In 4 cases cryptococci were demonstrated (Mucicarmine stain). There was one case each of Histoplasma capsulatum and leishmaniasis. One patient showed dense parasitemia with Plasmodium falciparum. One patient had immunoblastic lymphoma and showed bone marrow infiltration. Findings in this study strongly indicate that in HIV/AIDS, AFB stain should be done on each marrow aspirate to rule out tuberculosis in countries like India; where TB and AIDS are marching together.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Exame de Medula Óssea , Medula Óssea/microbiologia , Infecções por HIV/complicações , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/fisiopatologia , Adolescente , Adulto , Idoso , Biópsia por Agulha , Medula Óssea/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose/microbiologia
20.
Ultrasound Obstet Gynecol ; 24(5): 538-49, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15386612

RESUMO

OBJECTIVES: To examine the value of pre-induction sonographic assessment of cervical length, posterior cervical angle and occipital position in the prediction of the induction-to-delivery interval within 24 h, the likelihood of vaginal delivery within 24 h, the likelihood of Cesarean section and to compare sonographic assessment with the Bishop score. METHODS: In 604 singleton pregnancies, induction of labor was carried out at 35-42 weeks of gestation. Immediately before induction, transvaginal sonography was performed for measurement of cervical length and posterior cervical angle and a transabdominal scan was carried out to determine the position of the fetal occiput. The value of occipital position, posterior cervical angle, cervical length, parity, gestational age, maternal age, and body mass index (BMI) on the induction-to-delivery interval within 24 h, the likelihood of vaginal delivery within 24 h and the likelihood of Cesarean section were investigated by Cox proportional hazard model or logistic regression analysis. RESULTS: Vaginal delivery occurred in 484 (80.1%) women and this was within 24 h of induction in 388 (64.2%). Cesarean section was performed in 120 (19.9%). Occiput-anterior (OA) and transverse (OT) positions were analyzed as one group as the odds ratios (OR) and the HR were similar and different from occiput-posterior (OP), which was analyzed as another group. Prediction of the induction-to-delivery interval was provided by the occipital position, pre-induction cervical length, parity and posterior cervical angle. Prediction of the likelihood of vaginal delivery within 24 h was provided by the occipital position, cervical length, posterior cervical angle and BMI. Prediction of the likelihood of Cesarean section was provided by the occipital position, cervical length, parity, maternal age and BMI. In the prediction of vaginal delivery within 24 h, for a specificity of 75%, the sensitivity for ultrasound findings was 89% and for the Bishop score it was 65%. The respective sensitivities for Cesarean section were 78% and 53%. CONCLUSION: In women undergoing induction of labor, significant independent prediction of the induction-to-delivery interval within 24 h, the likelihood of vaginal delivery within 24 h and the likelihood of Cesarean section are provided by pre-induction cervical length, occipital position, posterior cervical angle and maternal characteristics. Sonographic parameters were superior to the Bishop score in the prediction of the outcome of induction.


Assuntos
Colo do Útero/anatomia & histologia , Trabalho de Parto Induzido/métodos , Complicações na Gravidez/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Índice de Massa Corporal , Colo do Útero/diagnóstico por imagem , Cesárea , Feminino , Humanos , Paridade , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Estudos Prospectivos
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