Subject(s)
Hemorrhage , Oocyte Retrieval , Adult , Embryo Transfer , Factor VIII/analysis , Factor VIII/therapeutic use , Female , Fertilization in Vitro , Frameshift Mutation , Hemophilia A/blood , Hemophilia A/diagnosis , Hemophilia A/drug therapy , Hemophilia A/genetics , Hemorrhage/prevention & control , Humans , von Willebrand Disease, Type 1/blood , von Willebrand Disease, Type 1/diagnosis , von Willebrand Disease, Type 3/blood , von Willebrand Disease, Type 3/diagnosis , von Willebrand Factor/analysisABSTRACT
Background The measurement of oestradiol is an integral component for the management of ovarian stimulation for in vitro fertilization. Automated immunoassays offer fast assay times and high throughput, with less sensitivity and specificity. The aim of this study is to optimize the oestradiol assay in patients undergoing ovarian stimulation for in vitro fertilization via comparison of oestradiol values obtained using two immunoassays compared with mass spectrometry. Methods Patients undergoing ovarian stimulation were prospectively recruited. Serum samples were analysed with ADVIA Centaur® CP Immunoassay, Abbott Architect i1000® immunoassay and AB Sciex 5500 liquid chromatography-tandem mass spectrometry (LC-MS/MS) systems. Per cent bias was determined for each system to report the average tendency of the values to be larger or smaller than the LC-MS/MS value. Linear regression of total follicular volume and oestradiol was computed. Results The ADVIA Centaur® CP assay had a positive bias of 20% compared with LC-MS/MS, while the Architect i1000® had a non-significant, negative bias of 0.3%. With regression fit, a clear, positive relationship was seen between follicular volume and oestradiol. The Architect i1000® assay had a greater correlation (R2 = 0.46) compared with Centaur® CP (R2 = 0.36), when oestradiol values were >1000 pg/mL (3670 pmol/L). Conclusions The Abbott Architect i1000® oestradiol assay exhibits greater agreement with LC-MS/MS and exhibited better correlation to follicular volume when oestradiol values are >1000 pg/mL (3670 pmol/L), prompting a change in the clinic's oestradiol platform. Attention to assay quality assurance via LC-MS/MS can improve the oestradiol accuracy and permit more informed clinical decisions for improved patient outcomes.
Subject(s)
Estradiol/blood , Fertilization in Vitro , Chromatography, Liquid , Female , Humans , Prospective Studies , Reproducibility of Results , Tandem Mass SpectrometryABSTRACT
Recently, our laboratory demonstrated that Stat3 is required for the de novo development of chemically-induced skin tumors. We have further investigated the role of Stat3 in epithelial carcinogenesis using mice in which the expression of a constitutively active/dimerized form of Stat3 (Stat3C) is targeted to the proliferative compartment of epidermis (referred to as K5.Stat3C transgenic mice). Keratinocytes from K5.Stat3C mice showed increased survival following exposure to 7,12-dimethylbenz[a]anthracene (DMBA) and enhanced proliferation following exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). In two-stage chemical carcinogenesis experiments using DMBA as the tumor initiator and TPA as the promoter, K5.Stat3C mice developed skin tumors with a shorter latency and in much greater number compared to non-transgenic littermates. Remarkably, 100% of the skin tumors that developed in K5.Stat3C transgenic mice bypassed the premalignant stage and were initially diagnosed as carcinoma in situ which rapidly progressed to squamous cell carcinoma (SCC). These tumors were highly vascularized, poorly differentiated and invasive and loss of expression of K10, filaggrin and E-cadherin was observed by 20 weeks. Finally, overexpression of Stat3C in a papilloma cell line led to enhanced cell migration and enhanced invasion through Matrigel in both the absence and presence of growth factors. In addition to its critical role in early stages of epithelial carcinogenesis, the current study reveals a novel role for Stat3 in driving malignant progression of skin tumors in vivo.
Subject(s)
Cell Transformation, Neoplastic/chemically induced , Epidermis/metabolism , STAT3 Transcription Factor/biosynthesis , STAT3 Transcription Factor/genetics , Skin Neoplasms/pathology , 9,10-Dimethyl-1,2-benzanthracene/toxicity , Animals , Apoptosis/drug effects , Cell Line, Tumor , Disease Models, Animal , Disease Progression , Epidermis/pathology , Keratinocytes/drug effects , Keratinocytes/metabolism , Keratinocytes/pathology , Mice , Mice, Transgenic , STAT3 Transcription Factor/physiology , Skin Neoplasms/chemically induced , Skin Neoplasms/genetics , Tetradecanoylphorbol Acetate/toxicityABSTRACT
Twenty-one oral Streptococcus isolates of known interbacterial coaggregation groups were tested against one another (as both producers and indicators) to detect bacteriocin-like inhibitory activity. In agar-based antagonism tests, seven strains produced small inhibitory zones (< or = 3 mm diameter) but in liquid medium, only strain Streptococcus gordonii DL1 (Challis) produced a detectable antibacterial action (bacteriocin STH1). Five strains were sensitive to bacteriocin STH1, but neither the production of nor the sensitivity to any of the antagonistic agents correlated with coaggregation groupings. Four strains (C219, 903, 118 and Wicky) developed stable resistance in response to the bacteriocin, whereas one isolate (strain 34) remained sensitive following repeated bacteriocin exposure. With one exception (strain 903), bacteriocin STH1-sensitive strains were competent for genetic transformation, but not all competent strains were bacteriocin-sensitive. Bacteriocin-resistant derivatives of transformable strains exhibited decreased competence (80-90% reduction) compared with their parent strains.