Special Issue New Insights Into Microaneurysms in the Deep Capillary Plexus Detected by Optical Coherence Tomography Angiography in Diabetic Macular Edema

PURPOSE. To study the association between the distributions of microaneurysms detected by en face optical coherence tomography angiography (OCTA) and diabetic macular edema (DME). METHODS. The study design was a retrospective chart review of 27 patients (33 eyes) with DME. The eyes were scanned using OCTA (6 3 6 mm) and spectral-domain (SD) OCT macular cube. Each of the images of the capillary plexus was overlaid onto the image of the topographic map, and the densities of the microaneurysms were measured by ImageJ software. The association between the distribution of microaneurysms and macular edema was evaluated. RESULTS. For microaneurysms in areas with and without edema, 77.3 6 8.1% of these microaneurysms were located in the deep capillary plexuses (DCP). However, in areas of edema where the retinal thickness was more than 400 lm, 91.3 6 9.1% of the microaneurysms were found in the DCP. This difference was statistically significant (P < 0.001). In the macular edema area, there was a significantly higher density of microaneurysms in the DCP compared to the superficial capillary plexuses (1.71/mm 2 vs. 0.17/mm 2 , P < 0.001). There was also a significant correlation between the macular volume and the density of microaneurysms in the DCP in edema (r ¼ 0.63, P < 0.001). CONCLUSIONS. Our study demonstrated a high proportion of microaneurysms in the DCP, as well as a novel association between the distributions of microaneurysms detected by OCTA and DME. Results also indicated that microaneurysms located in the DCP contribute to the pathogenesis of DME

Loss of Parp-1 affects gene expression profile in a genome-wide manner in ES cells and liver cells

BACKGROUND: Many lines of evidence suggest that poly(ADP-ribose) polymerase-1 (Parp-1) is involved in transcriptional regulation of various genes as a coactivator or a corepressor by modulating chromatin structure. However, the impact of Parp-1-deficiency on the regulation of genome-wide gene expression has not been fully studied yet. RESULTS: We employed a microarray analysis covering 12,488 genes and ESTs using mouse Parp-1-deficient (Parp-1(-/-)) embryonic stem (ES) cell lines and the livers of Parp-1(-/- )mice and their wild-type (Parp-1(+/+)) counterparts. Here, we demonstrate that of the 9,907 genes analyzed, in Parp-1(-/- )ES cells, 9.6% showed altered gene expression. Of these, 6.3% and 3.3% of the genes were down- or up-regulated by 2-fold or greater, respectively, compared with Parp-1(+/+ )ES cells (p < 0.05). In the livers of Parp-1(-/- )mice, of the 12,353 genes that were analyzed, 2.0% or 1.3% were down- and up-regulated, respectively (p < 0.05). Notably, the number of down-regulated genes was higher in both ES cells and livers, than that of the up-regulated genes. The genes that showed altered expression in ES cells or in the livers are ascribed to various cellular processes, including metabolism, signal transduction, cell cycle control and transcription. We also observed expression of the genes involved in the pathway of extraembryonic tissue development is augmented in Parp-1(-/- )ES cells, including H19. After withdrawal of leukemia inhibitory factor, expression of H19 as well as other trophoblast marker genes were further up-regulated in Parp-1(-/- )ES cells compared to Parp-1(+/+ )ES cells. CONCLUSION: These results suggest that Parp-1 is required to maintain transcriptional regulation of a wide variety of genes on a genome-wide scale. The gene expression profiles in Parp-1-deficient cells may be useful to delineate the functional role of Parp-1 in epigenetic regulation of the genomes involved in various biological phenomena

Medical Treatment of Echinococcus multilocularis and New Horizons for Drug Discovery: Characterization of Mitochondrial Complex II as a Potential Drug Target

As an efficient drug for alveolar echinococcosis (AE) is still not available, new chemotherapy targets are necessary. The mitochondrial respiratory chain may be a good drug candidate because parasite respiratory chains are quite different from those of mammalian hosts. For example, Ascaris suum possesses an NADH‐fumarate reductase system (fumarate respiration) that is highly adapted to anaerobic environments such as the small intestine. It is composed of mitochondrial complex I (NADH‐ubiquinone reductase), complex II (succinate‐ubiquinone reductase), and rhodoquinone. We previously demonstrated that fumarate respiration is also essential in E. multilocularis. Quinazoline, a complex I inhibitor, inhibited growth of E. multilocularis larvae in vitro. These results indicate that fumarate respiration could be a target for E. multilocularis therapy. In the current chapter, we focused on complex II, which is another component of this system, because quinazoline exhibited strong toxicity to mammalian mitochondria. We evaluated the molecular and biochemical characterization of E. multilocularis complex II as a potential drug target. In addition, we found that ascofuranone, a trypanosome cyanide‐insensitive alternative oxidase inhibitor, inhibited E. multilocularis complex II at the nanomolar order. Our findings demonstrate the potential development of targeted therapy against Echinococcus complex II

A consortium study of Antarctic micrometeorites recovered from the Dome Fuji Station

Deposits in the water tank at the Dome Fuji Station were collected by the 37th Japanese Antarctic Research Expedition team in 1996. We recovered 233 micrometeorites from the deposits. A consortium study was started in late 1998 to investigate mineralogy, petrology, bulk chemistry, and isotopic compositions of the micrometeorites. This is the first case of an organized study of micrometeorites in Japan, in order to establish the methods to investigate micrometeorites routinely. Consortium results on mineralogy, petrology, minor and trace element compositions, isotopic compositions of noble gases of the micrometeorites are reported in this volume. We also found a sequence of mineralogical and compositional changes of micrometeorites experienced from frictional heating during atmospheric entry. INAA and ion probe studies are now in progress

Mexiletine infusion challenge test for neonatal long QT syndrome with 2:1 atrioventricular block

For applying a genotype‐based treatment in neonatal long QT syndrome (LQTS), early detection of the genotype becomes an important issue. We report a case of a neonate with LQTS type 3 that presented with 2:1 atrioventricular block and underwent a mexiletine infusion challenge test, and achieved shortening of the QTc and 1:1 atrioventricular conduction. The mexiletine infusion challenge test was helpful to make an early detection of the genotype of the LQTS and predicted the drug efficacy in a neonatal patient

General characterization of Antarctic micrometeorites collected by the 39th Japanese Antarctic Research Expedition: Consortium studies of JARE AMMs (III)

From November 1998 to January 1999,the 39th Japanese Antarctic Research Expedition (JARE-39) undertook Japanese first large-scale collection of Antarctic micrometeorites (AMMs), with sizes larger than 10μm, at the Meteorite Ice Field around the Yamato Mountains in Antarctica (at three different locations, for a total of 24 collection sites). The number of collected AMMs larger than 40μm is estimated to be about 5000. Here we present the general characterization (i.e., micro-morphology and surface chemical composition using SEM/EDS) of &acd;810 AMMs chosen from 5 of the 24 sites. Additionally, the mineral composition of 61 out of 810 AMMs was determined by Synchrotron X-ray radiation. Preliminary results on mineralogical and chemical compositions show similarities with that of previous studies, even though a pronounced alteration of some AMMs is noticed. A correlation is found between the Mg/Si ratio at the sample\u27s surfaces of unmelted AMMs and the age of snow/ice in which the AMMs are embedded

Prenatal Diagnosis of Atrioventricular Block and QT Interval Prolongation by Fetal Magnetocardiography in a Fetus with Trisomy 18 and SCN5A R1193Q Variant

We report a case of fetal trisomy 18 with SCN5A R1193Q variant that presented with sinus bradycardia, 2 : 1 atrioventricular block (AVB), and QT interval prolongation. These complex arrhythmias were diagnosed by fetal magnetocardiography combined with ultrasound findings. Advanced AVB and ventricular arrhythmias were confirmed after birth. Genetic testing of the baby revealed a SCN5A R1193Q variant, which we considered could account for the various arrhythmias in this case

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Altered expression of a putative progenitor cell marker DCAMKL1 in the rat gastric mucosa in regeneration, metaplasia and dysplasia

<p>Abstract</p> <p>Background</p> <p>Doublecortin and calcium/calmodulin-dependent protein kinase-like-1 (DCAMKL1) is a candidate marker for progenitor cells in the gastrointestinal mucosa. Lineage cells in the gastric mucosa are derived from progenitor cells, but this process can be altered after injury. Therefore, we explored DCAMKL1 expression under pathological conditions.</p> <p>Methods</p> <p>An immunohistochemical analysis was performed in rat stomach with acute superficial injury, chronic ulcer, intestinal metaplasia and dysplasia.</p> <p>Results</p> <p>DCAMKL1 was exclusively expressed in immature quiescent cells in the isthmus of normal fundic glands, where putative progenitor cells are thought to reside. DCAMKL1-positive cells and proliferating cells shed into the lumen after superficial injury and re-appeared during the regenerative process, mainly in the superficial mucosa. In the marginal mucosa around the active ulcer, parietal and chief cells diminished, foveolar hyperplasia was evident, and trefoil factor family 2 (TFF2)/spasmolytic polypeptide-expressing metaplasia (SPEM) emerged at the gland base. DCAMKL1 cells re-emerged in the deep mucosa juxtaposed with SPEM and proliferating cells. In the healing ulcer, the TFF2 cell population expanded and seemed to redifferentiate to chief cells, while proliferating cells and DCAMKL1 cells appeared above and below the TFF2 cells to promote healing. SPEM appeared and PCNA cells increased in the intestinalized mucosa, and DCAMKL1 was expressed in the proximity of the PCNA cells in the deep mucosa. DCAMKL1, PCNA and TFF2 were expressed in different dysplastic cells lining dilated glands near SPEM.</p> <p>Conclusion</p> <p>The ultrastructural appearance of DCAMKL1-positive cells and the expression patterns of DCAMKL1 in normal and pathological states indicate that the cells belong to a progenitor cell population. DCAMKL1 expression is closely associated with TFF2/SPEM cells after injury. DCAMKL1 cells repopulate close to proliferating, hyperplastic, metaplastic and dysplastic cells, and the progenitor zone shifts according to the pathological circumstances.</p