152 research outputs found

    Promulgation of Navigational Warnings Under the Global Maritime Distress and Safety System

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    The Global Maritime Distress and Safety System (GMDSS), adopted in 1988, was developed under the auspices of the International Maritime Organization (IMO). The GMDSS will improve the dissemination and receipt of Maritime Safety Information (MSI) by vessels at sea and appropriate shore facilities equipped to render search and rescue coordination to shipping. Operational service of GMDSS began on 1 February 1992, with full implementation scheduled for 1 February 1999. Although there are seven basic categories of MSI within the GMDSS, this paper will focus on the promulgation of long range and coastal navigational warnings, which are coordinated through the International Hydrographic Organization (IHO)

    World Vector Shoreline

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    The Defense Mapping Agency (DMA) has developed a digital data file at a nominal scale of 1:250,000, containing shorelines, international boundaries and country names and known as the World Vector Shoreline (WVS). The file was developed with these features in support of geographic information systems, command, control and communications systems. The WVS has been designed to fit varying applications and is convertible to other system specific formats

    Variations of the UNC13D gene in patients with autoimmune lymphoproliferative syndrome.

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    Autoimmune lymphoproliferative syndrome (ALPS) is caused by genetic defects decreasing Fas function and is characterized by lymphadenopathy/splenomegaly and expansion of CD4/CD8 double-negative T cells. This latter expansion is absent in the ALPS variant named Dianzani Autoimmune/lymphoproliferative Disease (DALD). In addition to the causative mutations, the genetic background influences ALPS and DALD development. We previously suggested a disease-modifying role for the perforin gene involved in familial hemophagocytic lymphohistiocytosis (FHL). The UNC13D gene codes for Munc13-4, which is involved in perforin secretion and FHL development, and thus, another candidate for a disease-modifying role in ALPS and DALD. In this work, we sequenced UNC13D in 21 ALPS and 20 DALD patients and compared these results with sequences obtained from 61 healthy subjects and 38 multiple sclerosis (MS) patients. We detected four rare missense variations in three heterozygous ALPS patients carrying p.Cys112Ser, p.Val781Ile, and a haplotype comprising both p.Ile848Leu and p.Ala995Pro. Transfection of the mutant cDNAs into HMC-1 cells showed that they decreased granule exocytosis, compared to the wild-type construct. An additional rare missense variation, p.Pro271Ser, was detected in a healthy subject, but this variation did not decrease Munc13-4 function. These data suggest that rare loss-of-function variations of UND13D are risk factors for ALPS development

    Synthesis and Evaluation of 99mTc-Labelled Monoclonal Antibody 1D09C3 for Molecular Imaging of Major Histocompatibility Complex Class II Protein Expression

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    Purpose: It is known that major histocompatibility complex class II protein HLA-DR is highly expressed in B-cell lymphomas and in a variety of autoimmune and inflammatory diseases. Therefore, a radiolabelled fully humanized IgG4 monoclonal antibody (mAb) can provide useful prognostic and diagnostic information. Aims of the present study were to radiolabel an anti-HLA-DR mAb with technetium-99m and to evaluate its binding specificity, tissue distribution and targeting potential. Procedures: For labelling, we compared a direct method, after 2-mercaptoethanol (2-ME) reduction of disulphide bonds, with a two-step labelling method, using a heterobifunctional succinimidyl-6-hydrazinonicotinate hydrochloride chelator. Several in vitro quality controls and in vivo experiments in mice were performed. Results: We obtained highest labelling efficiency (LE, 998%) and specific activity (SA; 5,550 MBq/mg) via the direct method. In vitro quality control showed good stability, structural integrity and retention of the binding properties of the labelled mAb. The biodistribution in mice showed high and persistent uptake in spleen and suggests kidney and liver-mediated clearanc

    Thyroid Cancer Imaging In Vivo by Targeting the Anti-Apoptotic Molecule Galectin-3

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    Background The prevalence of thyroid nodules increases with age, average 4-7% for the U.S.A. adult population, but it is much higher (19-67%) when sub-clinical nodules are considered. About 90% of these lesions are benign and a reliable approach to their preoperative characterization is necessary. Unfortunately conventional thyroid scintigraphy does not allow the distinction among benign and malignant thyroid proliferations but it provides only functional information (cold or hot nodules). The expression of the anti-apoptotic molecule galectin-3 is restricted to cancer cells and this feature has potential diagnostic and therapeutic implications. We show here the possibility to obtain thyroid cancer imaging in vivo by targeting galectin-3. Methods The galectin-3 based thyroid immuno-scintigraphy uses as radiotracer a specific 99mTc-radiolabeled mAb. A position-sensitive high-resolution mini-gamma camera was used as imaging capture device. Human galectin-3 positive thyroid cancer xenografts (ARO) and galectin-3 knockout tumors were used as targets in different experiments in vivo. 38 mice with tumor mass of about 1 gm were injected in the tail vein with 100 ?Ci of 99mTc-labeled mAb to galectin-3 (30 ?g protein/in 100 ?l saline solution). Tumor images were acquired at 1 hr, 3 hrs, 6 hrs, 9 hrs and 24 hrs post injection by using the mini-gamma camera. Findings Results from different consecutive experiments show an optimal visualization of thyroid cancer xenografts between 6 and 9 hours from injection of the radiotracer. Galectin-3 negative tumors were not detected at all. At 6 hrs post-injection galectin-3 expressing tumors were correctly visualized, while the whole-body activity had essentially cleared. Conclusions These results demonstrate the possibility to distinguish preoperatively benign from malignant thyroid nodules by using a specific galectin-3 radio-immunotargeting. In vivo imaging of thyroid cancer may allow a better selection of patients referred to surgery. The possibility to apply this method for imaging and treatment of other galectin-3 expressing tumors is also discussed

    Role of Nuclear Imaging to Understand the Neural Substrates of Brain Disorders in Laboratory Animals: Current Status and Future Prospects

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    Molecular imaging, which allows the real-time visualization, characterization and measurement of biological processes, is becoming increasingly used in neuroscience research. Scintigraphy techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provide qualitative and quantitative measurement of brain activity in both physiological and pathological states. Laboratory animals, and rodents in particular, are essential in neuroscience research, providing plenty of models of brain disorders. The development of innovative high-resolution small animal imaging systems together with their radiotracers pave the way to the study of brain functioning and neurotransmitter release during behavioral tasks in rodents. The assessment of local changes in the release of neurotransmitters associated with the performance of a given behavioral task is a turning point for the development of new potential drugs for psychiatric and neurological disorders. This review addresses the role of SPECT and PET small animal imaging systems for a better understanding of brain functioning in health and disease states. Brain imaging in rodent models faces a series of challenges since it acts within the boundaries of current imaging in terms of sensitivity and spatial resolution. Several topics are discussed, including technical considerations regarding the strengths and weaknesses of both technologies. Moreover, the application of some of the radioligands developed for small animal nuclear imaging studies is discussed. Then, we examine the changes in metabolic and neurotransmitter activity in various brain areas during task-induced neural activation with special regard to the imaging of opioid, dopaminergic and cannabinoid receptors. Finally, we discuss the current status providing future perspectives on the most innovative imaging techniques in small laboratory animals. The challenges and solutions discussed here might be useful to better understand brain functioning allowing the translation of preclinical results into clinical applications

    Feasibility study of a computer-assisted radioguided surgery system

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    This paper deals with the study of a system prototype that can be used as an auxiliary tool in radioguided surgery methods. The use of new technologies in radioguided surgery concern the exact positioning of the lesion to be exerted. This is possible, in operation theatre, thanks to portable scintigraphics devices or to radiation counters. Due to lack of a coordinate system in the operation field, it is difficult for the surgeon to localize the pathology after removing the detection instrument. The system proposed in this paper is composed mainly of three elements: a handheld, high-resolution gamma camera with a small Field Of View (FOV) based on Hamamatsu R8900-00-C12 Position Sensitive Photomultiplier Tube (PSPMT), a laser scanner for the reconstruction of the body district and a stereoscopic system for contactless surgical tool tracking. Analyzing a set of scintigraphic images, taken from different projections, it is possible to localize the three-dimensional position of the lesion. Thanks to the use of the scanner and image fusion techniques, the pathology is shown on a PC monitor correctly positioned with respect to the body surface. Using a couple of stereoscopic cameras, the surgical tool can be tracked and shown on the same monitor, so that the surgeon can know the instantaneous relative position between the tool and the pathology. Exploiting these systems, a navigation system prototype has been developed that is suitable for radioguided surgical application. (c) 2007 Elsevier B.V. All rights reserved
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