Evaluation of dengue IgM detection tests using sera from patients with autoimmune diseases

Three commercial dengue IgM test kits and 'in-house' IgM-capture enzyme-linked immunosorbent assay (ELISA) were examined for false positive reactions, using 49 serum samples from patients with autoimmune diseases. All the samples were found to be negative by the 'in-house' IgM-capture ELISA. Five samples were determined to be positive by the immunochromatographic test and three of the five samples were also found positive by one commercial IgM-capture ELISA kit. These results suggest that a possibility of false positive reaction should be considered when serum samples from autoimmune disease patients are tested for dengue IgM by some commercial dengue IgM test kits.     

Implementation of continuous 3D whole-body PET scanning using on-the-fly Fourier rebinning

The continuous scanning mode in three-dimensional (3D) whole-body PET studies has the advantage of axial sensitivity uniformity over the majority of the axial FOV. However, this scan mode requires large data handling compared to conventional discrete scans. In this work, we have implemented and evaluated a new continuous 3D scan method using 'on-the-fly' Fourier rebinning. In this method, sinograms for the pair of rings are added in real-time into the sinograms of the incremented ring pairs by moving the bed axially one detector width at a time. For an N-ring scanner, 2N--1 sinograms are transferred to a host computer at each bed position and rebinned into direct two-dimensional (2D) sinograms using Fourier rebinning. Phantom and human studies showed that the axial image uniformity is achieved without degrading the axial resolution. This method can minimize the time for off-line data processing and makes the continuous 3D scan more feasible in clinical whole-body studies.     

Expression of cell adhesion molecule 1 in malignant pleural mesothelioma as a cause of efficient adhesion and growth on mesothelium

Cell adhesion molecule 1 (CADM1), formerly referred to as SgIGSF, TSLC1, or Necl-2, has been characterized as a mast-cell adhesion molecule that mediates efficient interactions with mesothelial cells. Here, we examined whether CADM1 might be involved in the diffuse tumor growth over the pleural surface that characterizes malignant pleural mesothelioma (MPM). Immunohistochemical and western blot analyses revealed that 14 (25%) of 57 MPMs expressed the full-length form of CADM1 on the cell membrane, but non-neoplastic mesothelial cells did not express it at all. The majority of available MPM cell lines also expressed the full-length form of CADM1. We compared CADM1-positive and -negative MPM cells in culture within soft agar and in coculture on mesothelial or fibroblastic monolayers. Within soft agar, CADM1-negative MPM cells were capable of forming colonies, whereas CADM1-positive cells were not, suggesting that CADM1 is a potential tumor suppressor of MPM, consistent with the past characterization of this molecule in other types of tumors. However, in coculture on mesothelial cell monolayers lacking full-length CADM1, CADM1-positive MPM cells spread more widely and grew more quickly, whereas the CADM1-negative cells piled up. Transfection of the CADM1-negative cells with CADM1 cDNA caused them to behave like the CADM1-positive cells, with faster, more widespread growth. These phenotypic differences were not detectable in cocultures on lung fibroblastic monolayers, in which all MPM cells grew much more slowly than on mesothelial cells, irrespective of CADM1 positivity. CADM1 thus appears to mediate efficient adhesion and growth of MPM cells specifically on mesothelial cells, probably via trans-heterophilic binding, and thus may be involved in the manifestation of a considerable subset of MPMs as diffusely growing tumors disseminated over the pleural surface.     

Putative tumor suppressor EDD interacts with and up-regulates APC

Adenomatous polyposis coli (APC), whose mutation causes colorectal cancers, is a key player in the Wnt signaling pathway. While the role of APC in inhibition of beta-catenin/LEF1-dependent activation of transformation-inducing genes has been intensively studied and well established, regulation of APC expression at the protein level is only partially understood. Here we report that APC is up-regulated by EDD, the mammalian orthologue of Drosophila melanogaster"hyperplastic discs" gene (hyd) that is considered to be a putative tumor suppressor. Screening of APC immunocomplexes by mass spectrometry identified EDD as a putative APC-interacting protein. Exogenously expressed and endogenous APC interacted with EDD in vivo. Indirect immunofluorescent analyses demonstrated that APC and EDD co-localized in the cytoplasm of the cell. Over-expression of EDD enhanced the protein expression level of APC and its binding partner Axin, resulting in inhibition of Wnt signaling downstream of beta-catenin. Conversely, siRNA knock-down of EDD down-regulated APC at the protein level without altering its mRNA level, causing enhanced protein expression of beta-catenin. Thus, through protein-protein interaction, EDD stabilizes APC and up-regulates APC's function to inhibit beta-catenin, suggesting that EDD could act as a colorectal tumor suppressor.     

Feasibility of a self‐assembling peptide hydrogel scaffold for meniscal defect: An in vivo study in a rabbit model

The inner avascular zone of the meniscus has limited healing capacity as the area is poorly vascularized. Although peptide hydrogels have been reported to regenerate bone and cartilage, their effect on meniscus regeneration remains unknown. We tested whether the self‐assembling peptide hydrogel scaffold KI24RGDS stays in the meniscal lesion and facilitates meniscal repair and regeneration in an induced rabbit meniscal defect model. Full‐thickness (2.0 mm diameter) cylindrical defects were introduced into the inner avascular zones of the anterior portions of the medial menisci of rabbit knees (n = 40). Right knee defects were left empty (control group) while the left knee defects were transplanted with peptide hydrogel (KI24RGDS group). Macroscopic meniscus scores were significantly higher in the KI24RGDS group than in the control group at 2, 4, and 8 weeks after surgery. Histological examinations including quantitative and qualitative scores indicated that compared with the control group, the reparative tissue in the meniscus was significantly enhanced in the KI24RGDS group at 2, 4, 8, and 12 weeks after surgery. Immunohistochemical staining showed that the reparative tissue induced by KI24RGDS at 12 weeks postimplantation was positive for Type I and II collagen. KI24RGDS is highly biocompatible and biodegradable, with strong stiffness, and a three dimensional structure mimicking native extracellular matrix and RGDS sequences that enhance cell adhesion and proliferation. This in vivo study demonstrated that KI24RGDS remained in the meniscal lesion and facilitated the repair and regeneration in a rabbit meniscal defect model.     

Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors

The chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. The aim of this study was to develop a radiopharmaceutical for the imaging of CXCR4-expressing tumors in vivo. Based on structure-activity relationships, we designed a 14-residue peptidic CXCR4 inhibitor, Ac-TZ14011, as a precursor for radiolabeled peptides. For 111In-labeling, diethylenetriaminepentaacetic acid (DTPA) was attached to the side chain of d-Lys(8) which is distant from the residues indispensable for the antagonistic activity. In-DTPA-Ac-TZ14011 inhibited the binding of a natural ligand, stromal cell-derived factor-1alpha, to CXCR4 in a concentration-dependent manner with an IC50 of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more 111In-DTPA-Ac-TZ14011 accumulated in the CXCR4-expressing tumor than in blood or muscle. Furthermore, the tumor-to-blood and tumor-to-muscle ratios were significantly reduced by coinjection of Ac-TZ14011, indicating a CXCR4-mediated accumulation in tumor. These findings suggested that 111In-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo.     

Ophthalmic Artery Flow Pattern-related Stump Pressure and Ischemic Tolerance during Balloon Test Occlusion of the Internal Carotid Artery

Very few studies have described the blood flow pattern in the ipsilateral ophthalmic artery (OphA) during internal carotid artery (ICA) balloon test occlusion performed to estimate the risk of cerebral ischemia associated with therapeutic ICA sacrifice. This study aimed to investigate the relationship between ipsilateral OphA flow patterns just after ICA temporary occlusion and balloon test occlusion findings. We retrospectively reviewed 32 balloon test occlusion procedures performed at our institution between 2010 and 2019, and analyzed the OphA flow patterns and the conventional balloon test occlusion assessment items: neurological symptoms, stump pressure, stump-pressure ratio, collateral circulations, and venous phase delay. The flow patterns were categorized as type I (retrograde flow reaching the middle cerebral artery [MCA]), type II (retrograde flow to the ICA not reaching the MCA), or type III (no retrograde flow). Tolerance to balloon test occlusion was observed in 4/21 patients (19.0%), 4/6 patients (66.7%), and all five patients with types I, II, and III flows, respectively. The mean pressure ratios during balloon test occlusion in flow types I, II, and III were 35.6% ± 3.5%, 56.4% ± 6.5%, and 69.4% ± 7.1%, respectively (P <0.001). The mean stump pressures in flow types I, II, and III were 36.2 ± 3.6 mmHg, 46.6 ± 6.7 mmHg, and 66.6 ± 7.3 mmHg, respectively (P = 0.003). The mean venous phase delay in flow types I, II, and III were 0.99 ± 0.14 s, 0.25 ± 0.25 s, and 0.0 ± 0.28 s, respectively (P = 0.004). All the above variables showed significant flow-related differences. These results suggest that the OphA flow patterns may provide an additional diagnostic criterion for balloon test occlusion.     

Simple visualization of the corticospinal pathway using tractography: one-ROI and two-ROI methods

Diffusion tensor imaging (DTI), a magnetic resonance (MR) technique to analyze diffusion anisotropy of the brain, is able to demonstrate subtle white matter anatomy. Tractography is expected to be a unique, non-invasive tool to provide more pertinent insights into brain structure and orientation not accessible by conventional MRI. In this report, preliminary experiences of visualization of the corticospinal tract using tractography are described. DTI of the brain was performed in 5 normal volunteers using single-shot echo-planar imaging, then tractography was generated by our original software. We determined that the two-region-of-interest (ROI) method is superior to the one-ROI method.     

MR imaging of ischemic penumbra

Cerebral ischemic stroke is one of the most fatal diseases despite current advances in medical science. Recent demonstration of efficacy using intravenous and intra-arterial thrombolysis demands therapeutic intervention tailored to the physiologic state of the individual tissue and stratification of patients according to the potential risks for therapies. In such an era, the role of the neuroimaging becomes increasingly important to evaluate the extent and location of tissues at risk of infarction (ischemic penumbra), to distinguish it from unsalvageable infarcted tissues or doomed hemorrhagic parenchyma. In this review, we present briefly the current role and limitation of computed tomography and conventional magnetic resonance imaging (MRI). We also present the possible applications of advanced MR techniques, such as diffusion and perfusion imaging, concentrating on the delineation or detection of ischemic penumbra.