18,913 research outputs found

    Ultrasound-guided aspiration of cystic ovarian lesions

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    Introduction and Objective: In the last two decades the increased accuracy of ultrasonography has allowed simple ovarian cysts to be reliably identified. As clinical data suggest that simple cystic lesions rarely become malignant, surgical treatment of these cysts may therefore represent overtreatment. Our study aimed to evaluate the results of ultrasound (US) guided aspiration of cystic ovarian lesions performed in our institution in the last ten years

    Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

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    Copyright @ 2012 Nature Publishing GroupThis article has been made available through the Brunel Open Access Publishing Fund.Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund

    Nonconservative Lagrangian mechanics II: purely causal equations of motion

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    This work builds on the Volterra series formalism presented in [D. W. Dreisigmeyer and P. M. Young, J. Phys. A \textbf{36}, 8297, (2003)] to model nonconservative systems. Here we treat Lagrangians and actions as `time dependent' Volterra series. We present a new family of kernels to be used in these Volterra series that allow us to derive a single retarded equation of motion using a variational principle

    Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications.

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    Background: Diabetes mellitus is associated with pancreatic cancer in more than 80% of the cases. Clinical, epidemiological, and experimental data indicate that pancreatic cancer causes diabetes mellitus by releasing soluble mediators which interfere with both beta-cell function and liver and muscle glucose metabolism. Methods: We analysed, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media, pancreatic cancer patients' peripheral and portal sera, comparing them with controls and chronic pancreatitis patients' sera. Results: MALDI-TOF analysis of pancreatic cancer cells conditioned media and patients' sera indicated a low molecular weight peptide to be the putative pancreatic cancer-associated diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non-diabetic patients revealed the presence of a 1500 Da peptide only in diabetic patients. The amino acid sequence of this peptide corresponded to the N-terminal of an S-100 calcium binding protein, which was therefore suggested to be the pancreatic cancer-associated diabetogenic factor. Conclusions: We identified a tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100 calcium binding protein, which is probably the pancreatic cancer-associated diabetogenic facto

    Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?

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    BACKGROUND: Our aim was to identify the pancreatic cancer diabetogenic peptide. METHODS: Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. RESULTS: A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. CONCLUSIONS: The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus

    Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III

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    There are no known biological markers or technologies to predict the natural history of an individual CIN III. The probability of progression is considered greater with the persistence of high-risk human papillomavirus (HPV) infection and age. p53 polymorphism has been associated with cervical carcinogenesis. Hormone-induced cervical cancer is mediated by estrogen receptor (ER) and progesterone receptor (PR). In cervical cancer, increased bcl-2 and Bax immunoreactivity is generally associated with a better prognosis. The purpose of this study was to evaluate the value of HPV 16 and HPV 18 typing and p53 codon polymorphism genotyping by polymerase chain reaction and ER, PR, bcl-2, and Bax expression by immunohistochemistry in predicting the CIN III clinical behavior of CIN III lesions. We studied the expression of these prognostic factors in the CIN III adjacent to squamous cell microinvasive carcinomas of the cervix (MIC) from 29 patients with FIGO stage IA1 cervical cancer and in 25 patients with CIN III and no documented focus of invasion. In the MIC group, only the CIN III was considered at least 2 mm away from the microinvasive complex. The ER, PR, bcl-2, and Bax immunoreactivity was scored as positive (>10% staining cells) and negative (<10% staining cells). No significant difference was observed between MIC and CIN III group concerning HPV infection and p53 polymorphism. The ER, PR, bcl-2, and Bax immunohistochemical expression was stronger and more frequent in the CIN III group. After multivariable analysis, coexpression of ER, PR, and bcl-2 was the only independent factor in defining low risk of progression for CIN III. Our study suggests that coexpression of ER, PR, and bcl-2 may be a useful tool in identifying the CIN III lesions with low risk of progression to cervical cance

    Descrição de uma forma autossômica dominante de síndrome de Kabuki por mutação no gene MLL2

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    Aims: Although there are more than 400 cases of Kabuki syndrome described in the literature, it is believed that this syndrome is under-diagnosed. Most cases occur sporadically, despite cases with autosomal dominant familial transmission being described. Here we describe three cases identified in the same family. Cases description: A family (mother and two children) was diagnosed with Kabuki syndrome. The three patients show the typical characteristics (facial appearance, musculoskeletal abnormalities, cognitive impairment, growth retardation and peculiar dermatoglyphic pattern) associated with other anomalies described in the syndrome (congenital heart disease and increased susceptibility to infections). Genetic studies revealed a nonsense mutation c.14710 C > T (p.Arg4904X) in the MLL2 gene in the three members of the family. Conclusions: With the description of another case of familial Kabuki syndrome, the authors wish to illustrate the autosomal dominant inheritance with variable expressivity, which are present in this situation, and to alert to the need for a rigorous clinical and molecular evaluation of the affected patient’s relatives, allowing appropriate genetic counseling
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