ABSTRACT
BACKGROUND: This study evaluated the clinical efficacy of a novel imaging system (HyperEye Medical System [HEMS]; Mizuho Corp., Tokyo, Japan) that uses the near-infrared (NIR) fluorescence of indocyanine green to analyze sentinel lymph node (SLN) biopsies for the staging of breast cancer. METHODS: This study enrolled 91 patients with histologically confirmed breast cancer that was clinically node negative with a tumor size <3 cm. We compared SLN identification rates between HEMS and conventional methods (gamma probe scanning using a colloidal radioisotope [RI] and a blue dye method) by analyzing the relationships of lymphatic to axillary lesions and SLNs. RESULTS: The identification rate of SLNs was 100% using HEMS, 97.8% using the RI method, and 95.6% using the blue dye method. Two types of lymphatic pathway (LP) were detected in 39 patients (42.9%) and also clearly identified using HEMS-captured color and NIR fluorescence. The incidence of two or more SLNs was significantly higher in patients with a two-route LP to the axilla group than in those with only one route (p < 0.001; 43.6 vs. 9.6%). CONCLUSIONS: The HEMS NIR fluorescence color imaging method is a promising potential modality for higher-level identification of SLNs than a standard combination of the RI and blue dye methods.
Subject(s)
Breast Neoplasms/pathology , Sentinel Lymph Node/pathology , Adult , Aged , Axilla/pathology , Female , Fluorescence , Humans , Indocyanine Green/administration & dosage , Lymphatic Metastasis/pathology , Middle Aged , Radionuclide Imaging/methods , Sentinel Lymph Node Biopsy/methodsABSTRACT
Human pluripotent stem cells are considered to be ideal cell sources for regenerative medicine, but their clinical and industrial application is hindered by their tumorigenic potential. Previously we have identified a pluripotent stem cell-specific lectin rBC2LCN recognizing podocalyxin as a cell surface ligand. More recently, podocalyxin was found to be a soluble ligand of rBC2LCN that is secreted specifically from human pluripotent stem cells into cell culture media. Taking advantage of this phenomenon, we have previously developed a sandwich assay targeting the soluble podocalyxin using rBC2LCN as a capturing probe and another lectin rABA as an overlay probe to detect human pluripotent stem cells residing in cell therapy products derived from human pluripotent stem cells. A drawback to this, however, was that cell culture media containing fetal bovine serum was found to cause a substantial background signal to the sandwich assay. To reduce the background and increase the sensitivity, we screened different overlay probes to detect the soluble podocalyxin. Among them, an anti-keratan sulfate monoclonal antibody called R-10G showed the highest sensitivity and provided a low background signal to fetal bovine serum. The established sandwich assay using rBC2LCN and R-10G was proved to be powerful, which allowed the high-sensitive detection of human induced pluripotent stem cells residing among clinical-grade cardiomyocytes and neural stem cells, both derived from human induced pluripotent stem cells. The developed method has a possibility to be a standard technology to detect human induced pluripotent stem cells resided in various types of cell therapy products.
ABSTRACT
INTRODUCTION: An accurate differential diagnosis between single adenoma (SA) and multiglandular disease (MGD) remains difficult in Technetium-99m sestamibi scintigraphy (MIBI)-negative patients with primary hyperparathyroidism (PHPT). The aim of the present study was to evaluate the minimally invasive parathyroidectomy (MIP) in patients with PHPT. METHODS: Clinical records of 48 patients who underwent neck exploration between November 2002 and June 2012 in Kochi Medical School Hospital were reviewed retrospectively to identify candidates that underwent for MIP which was defined as the selective removal of a SA using less invasive surgery. RESULTS: The preoperative detection rate of lesions using ultrasonography, MIBI, computed tomography, and magnetic resonance imaging was 90%, 83%, 76%, and 55%, respectively. Although all 39 patients in the MIBI-positive group were diagnosed with an SA and subsequently underwent curative MIP, 3 patients in MIBI-negative group (n = 6) were MGD, who underwent neck exploration. Preoperative mean intact parathyroid hormone (419 pg/ml vs. 149 pg/ml; P < 0.01) and alkaline phosphatase levels (746 U/l vs. 277 U/l; P < 0.01) were significantly higher in the SA than MGD group. CONCLUSIONS: In MIBI-negative patients with indications for surgery, MIP should not be carried out without a clear localization of SA, or in MGD.
ABSTRACT
Animal microRNA sequences are subject to 3' nucleotide addition. Through detailed analysis of deep-sequenced short RNA data sets, we show adenylation and uridylation of miRNA is globally present and conserved across Drosophila and vertebrates. To better understand 3' adenylation function, we deep-sequenced RNA after knockdown of nucleotidyltransferase enzymes. The PAPD4 nucleotidyltransferase adenylates a wide range of miRNA loci, but adenylation does not appear to affect miRNA stability on a genome-wide scale. Adenine addition appears to reduce effectiveness of miRNA targeting of mRNA transcripts while deep-sequencing of RNA bound to immunoprecipitated Argonaute (AGO) subfamily proteins EIF2C1-EIF2C3 revealed substantial reduction of adenine addition in miRNA associated with EIF2C2 and EIF2C3. Our findings show 3' addition events are widespread and conserved across animals, PAPD4 is a primary miRNA adenylating enzyme, and suggest a role for 3' adenine addition in modulating miRNA effectiveness, possibly through interfering with incorporation into the RNA-induced silencing complex (RISC), a regulatory role that would complement the role of miRNA uridylation in blocking DICER1 uptake.
