Angioscopic Evaluation of Thrombi in the Culprit Coronary Lesions in Patients With Acute Myocardial Infarction

The purpose of this study was to evaluate intracoronary thrombi in the culprit lesions in patients with acute myocardial infarction (AMI) by angioscopy, and to compare them with clinical and angiographic features. We angioscopically observed the culprit coronary lesions in 66 patients with AMI (55 males and 11 females, 63.9±15.4 years old) just before interventional therapy. Thrombi were observed in 42 of 66 lesions (64%), namely, red thrombi in 16, mixed thrombi in 15, white thrombi in 11. In patients with complete obstruction (TIMI grade 0 and I), red thrombi were more frequently observed than mixed or white thrombi. On the other hand, in patients with incomplete obstruction (TIMI grade II and III), white thrombi were more frequently observed than the others. Angiographically, haziness and filling defect were significantly more frequently observed in patients with red thrombi than the others (p<0.05). The distance from proximal side branch to thrombi tended to be longer in patients with red thrombi than the others. The time from onset of AMI tended to be longer in patients with white thrombi than the others. These results suggest that blood flow may be an important determinant of thrombi characterization

Combinatorial Roles of Heparan Sulfate Proteoglycans and Heparan Sulfates in Caenorhabditis elegans Neural Development

Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and adult physiology of all metazoan organisms. Most of the known molecular interactions of HSPGs are attributed to the structurally highly complex heparan sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan) contains HS modifications that differ from another HSPG (such as glypican) has remained largely unresolved. Here, a neural model in C. elegans is used to demonstrate for the first time the relationship between specific HSPGs and HS modifications in a defined biological process in vivo. HSPGs are critical for the migration of hermaphrodite specific neurons (HSNs) as genetic elimination of multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the migrating neuron and in the matrix, act in parallel to support neuron migration. Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6, function in a linear signaling pathway and glypican/lon-2 and HS 2-O-sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1 and hst-6. These results suggest core protein specific HS modifications that are critical for HSN migration. In C. elegans, the core protein specificity of distinct HS modifications may be in part regulated at the level of tissue specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic analysis reveals that there is a delicate balance of HS modifications and eliminating one HS modifying enzyme in a compromised genetic background leads to significant changes in the overall phenotype. These findings are of importance with the view of HS as a critical regulator of cell signaling in normal development and disease

Usefulness of Microcatheters Inserted Overnight for Additional Injection of Sclerosant after Initial Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices

In patients with large gastric varices, dose limitation of the sclerosant can cause difficulties in achieving complete thrombosis of varices during a single balloon-occluded retrograde transvenous obliteration (BRTO) procedure. For patients with incomplete variceal thrombosis after the first BRTO, additional sclerosant must be injected in a second BRTO. We report a successful case of BRTO for large gastric varices in whom additional sclerosant was injected through a microcatheter that remained inserted overnight. To achieve complete variceal thrombosis in a patient with incomplete thrombosis of large gastric varices after a first BRTO, a retained microcatheter can be used to inject additional sclerosant in a second BRTO the next day

10-kJ PW Laser for the FIREX-I Program

A 10-kJ PW laser (LFEX) is under construction for the FIREX-I program. This paper reports a design overview of LFEX, the technological development of a large-aperture arrayed amplifier with modified four-pass architecture, wavefront correction, a large-aperture Faraday rotator with a superconducting magnet, a new pulse compressor arrangement, and focus control

International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity

Beginning in 1970, a committee was constituted under the auspices of the World Health Organization (WHO) to catalog primary immunodeficiencies. Twenty years later, the International Union of Immunological Societies (IUIS) took the remit of this committee. The current report details the categorization and listing of 354 (as of February 2017) inborn errors of immunity. The growth and increasing complexity of the field have been impressive, encompassing an increasing variety of conditions, and the classification described here will serve as a critical reference for immunologists and researchers worldwide

Possibility of a White Dwarf as the Accreting Compact Star in CI Cam (= XTE J0421+560)

We present results from ASCA observations of the binary CI Cam both in quiescence and in outburst in order to identify its central accreting object. The quiescence spectrum of CI Cam consists of soft and hard components which are separated clearly at aound 2-3keV. A large equivalent width of an iron Ka emission line prefers an optically thin thermal plasma emission model to a non-thermal power-law model for the hard component, which favors a white dwarf as the accreting object, since the optically thin thermal hard X-ray emission is a common characteristic among cataclysmic variables (binaries including an accreting white dwarf). The outburst spectrum, on the other hand, is composed of a hard component represented by a multi-temperature optically thin thermal plasma emission and of an independent soft X-ray component that appears below 1 keV intermittently on a decaying light curve of the hard component. The spectrum of the soft component is represented well by a blackbody with the temperature of 0.07-0.12keV overlaid with several K-edges associated with highly ionized oxygen. This, together with the luminosity as high as ~1E38 erg/s is similar to a super-soft source (SSS). The outburst in the hard X-ray band followed by the appearance of the soft blackbody component reminds us of recent observations of novae in outburst. We thus assume the outburst of CI Cam is that of a nova, and obtain the distance to CI Cam to be 5-17kpc by means of the relation between the optical decay time and the absolute magnitude. This agrees well with a recent estimate of the distance of 5-9kpc in the optical band. All of these results from the outburst data prefer a white dwarf for the central object of CI Cam.Comment: 20 pages, 5 figures, to appear in the Astrophysical Journal v601, n2, February 1, 2004 issu

Maxadilan Prevents Apoptosis in iPS Cells and Shows No Effects on the Pluripotent State or Karyotype

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a structurally endogenous peptide with many biological roles. Maxadilan, a 61-amino acid vasodilatory peptide, specifically activates the PACAP type I receptor (PAC1). Although PAC1 has been identified in embryonic stem cells, little is known about its presence or effects in human induced pluripotent stem (iPS) cells. In the present study, we investigated the expression of PAC1 in human iPS cells by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analysis. To study the physiological effects mediated by PAC1, we evaluated the role of maxadilan in preventing apoptotic cell death induced by ultraviolet C (UVC). After exposure to UVC, the iPS cells showed a marked reduction in cell viability and a parallel increase of apoptotic cells, as demonstrated by WST-8 analysis, annexin V/propidium iodide (PI) analysis and the terminal transferase dUTP nick end labeling (TUNEL) assay. The addition of 30 nM of maxadilan dramatically increased iPS cell viability and reduced the percentage of apoptotic cells. The anti-apoptotic effects of maxadilan were correlated to the downregulation of caspase-3 and caspase-9. Concomitantly, immunofluorescence, western blot analysis, real-time quantitative polymerase chain reaction (RT-qPCR) analysis and in vitro differentiation results showed that maxadilan did not affect the pluripotent state of iPS cells. Moreover, karyotype analysis showed that maxadilan did not affect the karyotype of iPS cells. In summary, these results demonstrate that PAC1 is present in iPS cells and that maxadilan effectively protects iPS cells against UVC-induced apoptotic cell death while not affecting the pluripotent state or karyotype

Novel Mouse Xenograft Models Reveal a Critical Role of CD4+ T Cells in the Proliferation of EBV-Infected T and NK Cells

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients' PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rγnull strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Expression of the EBV nuclear antigen 1 (EBNA1), the latent membrane protein 1 (LMP1), and LMP2, but not EBNA2, in the engrafted cells is consistent with the latency II program of EBV gene expression known in CAEBV. High levels of human cytokines, including IL-8, IFN-γ, and RANTES, were detected in the peripheral blood of the model mice, mirroring hypercytokinemia characteristic to both CAEBV and EBV-HLH. Transplantation of individual immunophenotypic subsets isolated from patients' PBMC as well as that of various combinations of these subsets revealed a critical role of CD4+ T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases