Assessment of Canine Pancreas-Specific Lipase and Outcomes in Dogs with Hemodialysis-Dependent Acute Kidney Injury.

BackgroundRenal replacement therapies can be life-saving for dogs with severe acute kidney injury (AKI), however, comorbidities including pancreatitis might affect outcome.Hypothesis/objectivesTo investigate the prevalence of pancreas-specific lipase (Spec cPL) measurements consistent with pancreatitis (≥400 μg/L) in dogs undergoing intermittent hemodialysis (IHD) for treatment of AKI and to determine whether there were associations between 30-days outcomes and Spec cPL measurements.AnimalsFifty-three client-owned dogs presented to teaching hospitals between November 2008 and September 2016 that underwent IHD.MethodsRetrospective medical record review from dogs that received IHD for management of AKI and also had a Spec cPL measurement. Association between survival, dialysis-dependency, and Spec cPL measurements was assessed.ResultsForty of 53 (76%) dogs were alive at 30-days and 33/53(62%) had a Spec cPL result ≥400 μg/L. Spec cPL was not significantly different either between surviving (635.5 μg/L, range 29-1,001) and nonsurviving dogs (860 μg/L, range 56-1,001; P = 0.75) or between dialysis-dependent (1,001 μg/L, range 177-1,001) and nondialysis-dependent dogs (520 μg/L, range 29-1,001; P = 0.08). Spec cPL ≥400 μg/L was not significantly associated either with survival (P = 0.74) or dialysis-dependency (P = 0.33).Conclusions and clinical importanceResults revealed a high prevalence of Spec cPL ≥400 μg/L in dogs with AKI treated with IHD. No significant associations between Spec cPL and survival or dialysis-dependency in dogs with AKI at 30 days were identified in the current study, however, the latter could be due to lack of power in this study

The Diagnostic Value of Endoprobe for Small Esophageal Leiomyomas Derived from the Muscularis Mucosae

Esophageal leiomyoma derived from the muscularis mucosae (MM) is a rare condition, and the optimal modality for diagnosis and treatment is controversial. Endoscopic ultrasonography can provide an accurate image of esophageal layer structure, providing information on lesion suitability for potential endoscopic therapy. We attempted to investigate the diagnostic value of a transendoscopic balloon-tipped miniature ultrasonic endoprobe for small esophageal leiomyomas derived from MM. We resected 7 small esophageal leiomyomas derived from MM by endoscopic mucosal resection (EMR), all of which were diagnosed by a balloon-tipped endoprobe. The endosonographic and pathologic features of 7 cases of small esophageal leiomyomas derived from MM were compared. The balloon-tipped endoprobe clearly showed all 7 small esophageal leiomyomas derived from MM, even those under 5 mm in size (smallest lesion, 3.0 mm). The endosonographic characteristics of small esophageal leiomyomas derived from MM were a hypoechoic mass with smooth, regular, and a well-defined outer margin and homogenous inner echogram arising from the second hypoechoic layer. Complete resections were possible in all 7 cases by EMR without any complications. Tumor size was 3.0 - 13.5 mm (mean 7.8 mm) in maximum diameter. In all cases, endosonographic findings by endoprobe were exactly concordant with pathologic finding in determining the tumors depth in the esophageal wall, tissue origin and characteristics, growth pattern, and size. We detail the balloon-tipped endoprobe is a simple, convenient, and very useful in making accurate diagnosis of small esophageal leiomyomas derived from the MM and the appropriate applications of EMR

Divergent ancestral lineages of newfound hantaviruses harbored by phylogenetically related crocidurine shrew species in Korea

AbstractSpurred by the recent isolation of a novel hantavirus, named Imjin virus (MJNV), from the Ussuri white-toothed shrew (Crocidura lasiura), targeted trapping was conducted for the phylogenetically related Asian lesser white-toothed shrew (Crocidura shantungensis). Pair-wise alignment and comparison of the S, M and L segments of a newfound hantavirus, designated Jeju virus (JJUV), indicated remarkably low nucleotide and amino acid sequence similarity with MJNV. Phylogenetic analyses, using maximum likelihood and Bayesian methods, showed divergent ancestral lineages for JJUV and MJNV, despite the close phylogenetic relationship of their reservoir soricid hosts. Also, no evidence of host switching was apparent in tanglegrams, generated by TreeMap 2.0β

Hypernovae and Other Black-Hole-Forming Supernovae

During the last few years, a number of exceptional core-collapse supernovae (SNe) have been discovered. Their kinetic energy of the explosions are larger by more than an order of magnitude than the typical values for this type of SNe, so that these SNe have been called `Hypernovae'. We first describe how the basic properties of hypernovae can be derived from observations and modeling. These hypernovae seem to come from rather massive stars, thus forming black holes. On the other hand, there are some examples of massive SNe with only a small kinetic energy. We suggest that stars with non-rotating black holes are likely to collapse "quietly" ejecting a small amount of heavy elements (Faint supernovae). In contrast, stars with rotating black holes are likely to give rise to very energetic supernovae (Hypernovae). We present distinct nucleosynthesis features of these two types of "black-hole-forming" supernovae. Hypernova nucleosynthesis is characterized by larger abundance ratios (Zn,Co,V,Ti)/Fe and smaller (Mn,Cr)/Fe. Nucleosynthesis in Faint supernovae is characterized by a large amount of fall-back. We show that the abundance pattern of the most Fe deficient star, HE0107-5240, and other extremely metal-poor carbon-rich stars are in good accord with those of black-hole-forming supernovae, but not pair-instability supernovae. This suggests that black-hole-forming supernovae made important contributions to the early Galactic (and cosmic) chemical evolution.Comment: 49 pages, to be published in "Stellar Collapse" (Astrophysics and Space Science; Kluwer) ed. C. L. Fryer (2003

Deletion of Porcn in Mice Leads to Multiple Developmental Defects and Models Human Focal Dermal Hypoplasia (Goltz Syndrome)

Focal Dermal Hypoplasia (FDH) is a genetic disorder characterized by developmental defects in skin, skeleton and ectodermal appendages. FDH is caused by dominant loss-of-function mutations in X-linked PORCN. PORCN orthologues in Drosophila and mice encode endoplasmic reticulum proteins required for secretion and function of Wnt proteins. Wnt proteins play important roles in embryo development, tissue homeostasis and stem cell maintenance. Since features of FDH overlap with those seen in mouse Wnt pathway mutants, FDH likely results from defective Wnt signaling but molecular mechanisms by which inactivation of PORCN affects Wnt signaling and manifestations of FDH remain to be elucidated.We introduced intronic loxP sites and a neomycin gene in the mouse Porcn locus for conditional inactivation. Porcn-ex3-7flox mice have no apparent developmental defects, but chimeric mice retaining the neomycin gene (Porcn-ex3-7Neo-flox) have limb, skin, and urogenital abnormalities. Conditional Porcn inactivation by EIIa-driven or Hprt-driven Cre recombinase results in increased early embryonic lethality. Mesenchyme-specific Prx-Cre-driven inactivation of Porcn produces FDH-like limb defects, while ectodermal Krt14-Cre-driven inactivation produces thin skin, alopecia, and abnormal dentition. Furthermore, cell-based assays confirm that human PORCN mutations reduce WNT3A secretion.These data indicate that Porcn inactivation in the mouse produces a model for human FDH and that phenotypic features result from defective WNT signaling in ectodermal- and mesenchymal-derived structures

Expression of Epstein-Barr Virus Gene and Clonality of Infiltrated T Lymphocytes in Epstein-Barr Virus-associated Gastric Carcinoma

BACKGROUND: Epstein-Barr virus associated gastric lymphoepithelioma-like carcinoma (LELC) is characterized by the intensive infiltration of lymphoid cells, the presence of EBV, and the better prognosis over typical adenocarcinoma. Thus, it was assumable that viral latent proteins may be responsible for the recruitment of a certain T cell repertoire to EBV-associated gastric carcinoma. METHODS: To examine above possibility, EBV gene expression in gastric carcinoma tissues and usage of TCR among the tumor infiltrating lymphocytes were analyzed. RESULTS: EBV specific DNA and EBERs RNA were detected in 4 out of 30 patients. RT-PCR analysis revealed that all 4 of EBV-positive tumor tissues expressed EBNA1 mRNA and BARTs and LMP2a was detected only one sample out of 4. However, the EBNA2 and LMP-1 transcripts were not detected in these tissues. CD8(+) T cells were the predominant population of infiltrating lymphocytes in the EBV-positive gastric carcinoma. According to spectra type analysis of infiltrating T cells, 10 predominant bands were detected by TCR Vβ CDR3 specific RT-PCR from 4 EBV-positive tumor tissues. Sequence analysis of these bands revealed oligoclonal expansion of T cells. CONCLUSION: These findings suggest that clonally expanded T cells in vivo might be a population of cytotoxic T cells reactive to EBV-associated gastric carcinoma.ope

Overexpression of α(1,3)-fucosyltransferase VII is sufficient for the acquisition of lung colonization phenotype in human lung adenocarcinoma HAL-24Luc cells

Metastatic human lung adenocarcinoma HAL-8Luc cells display an enhanced expression of alpha(1,3)-fucosyltransferases (alpha(1,3)-Fuc-Ts) compared with their non-metastatic counterpart HAL-24Luc cells. This correlates with an increased surface expression of Lewis(x) (Le(x))- and Lewis(a) (Le(a))-related molecules and an in vitro enhanced adhesive capacity to E-selectin-expressing endothelial cells (Martin-Satué et al (1998). Cancer Res 58: 1544-1550). In the present work we have stably transfected HAL-24Luc cells with the cDNAs for the alpha(1,3)-Fuc-TIV and VII enzymes and analysed by flow cytometry the expression of Le(x), sialyl-Le(x), sialyl-Le(x) dimeric, Le(a) and sialyl-Le(a). Fuc-TVII transfectants exclusively overexpress sialyl-Le(x) while Fuc-TIV-transfected cells only overexpress the Le(x) oligosaccharide. We show that solely Fuc-TVII transfectants are able to adhere to interleukin-1beta-stimulated HUVEC monolayers. We also demonstrate that Fuc-TVII overexpression in HAL-24Luc cells is sufficient for the acquisition of the lung colonization phenotype. This is the first report directly showing the contribution of an alpha(1,3)-Fuc-T to the metastatic behaviour of human lung adenocarcinoma cells

Full-length Ebola glycoprotein accumulates in the endoplasmic reticulum

The Filoviridae family comprises of Ebola and Marburg viruses, which are known to cause lethal hemorrhagic fever. However, there is no effective anti-viral therapy or licensed vaccines currently available for these human pathogens. The envelope glycoprotein (GP) of Ebola virus, which mediates entry into target cells, is cytotoxic and this effect maps to a highly glycosylated mucin-like region in the surface subunit of GP (GP1). However, the mechanism underlying this cytotoxic property of GP is unknown. To gain insight into the basis of this GP-induced cytotoxicity, HEK293T cells were transiently transfected with full-length and mucin-deleted (Δmucin) Ebola GP plasmids and GP localization was examined relative to the nucleus, endoplasmic reticulum (ER), Golgi, early and late endosomes using deconvolution fluorescent microscopy. Full-length Ebola GP was observed to accumulate in the ER. In contrast, GPΔmucin was uniformly expressed throughout the cell and did not localize in the ER. The Ebola major matrix protein VP40 was also co-expressed with GP to investigate its influence on GP localization. GP and VP40 co-expression did not alter GP localization to the ER. Also, when VP40 was co-expressed with the nucleoprotein (NP), it localized to the plasma membrane while NP accumulated in distinct cytoplasmic structures lined with vimentin. These latter structures are consistent with aggresomes and may serve as assembly sites for filoviral nucleocapsids. Collectively, these data suggest that full-length GP, but not GPΔmucin, accumulates in the ER in close proximity to the nuclear membrane, which may underscore its cytotoxic property

Genetic Mapping of Social Interaction Behavior in B6/MSM Consomic Mouse Strains

Genetic studies are indispensable for understanding the mechanisms by which individuals develop differences in social behavior. We report genetic mapping of social interaction behavior using inter-subspecific consomic strains established from MSM/Ms (MSM) and C57BL/6J (B6) mice. Two animals of the same strain and sex, aged 10 weeks, were introduced into a novel open-field for 10 min. Social contact was detected by an automated system when the distance between the centers of the two animals became less than ~12 cm. In addition, detailed behavioral observations were made of the males. The wild-derived mouse strain MSM showed significantly longer social contact as compared to B6. Analysis of the consomic panel identified two chromosomes (Chr 6 and Chr 17) with quantitative trait loci (QTL) responsible for lengthened social contact in MSM mice and two chromosomes (Chr 9 and Chr X) with QTL that inhibited social contact. Detailed behavioral analysis of males identified four additional chromosomes associated with social interaction behavior. B6 mice that contained Chr 13 from MSM showed more genital grooming and following than the parental B6 strain, whereas the presence of Chr 8 and Chr 12 from MSM resulted in a reduction of those behaviors. Longer social sniffing was observed in Chr 4 consomic strain than in B6 mice. Although the frequency was low, aggressive behavior was observed in a few pairs from consomic strains for Chrs 4, 13, 15 and 17, as well as from MSM. The social interaction test has been used as a model to measure anxiety, but genetic correlation analysis suggested that social interaction involves different aspects of anxiety than are measured by open-field test