Clinicopathological features and the value of differential Cytokeratin 7 and 20 expression in resolving diagnostic dilemmas of ovarian involvement by colorectal adenocarcinoma and vice-versa

Introduction

Intravascular lesions of the hand comprise reactive and neoplastic entities. The clinical diagnosis of such lesions is often difficult, and usually requires pathologic examination. We present the largest series to date of intravascular lesions affecting the hand.

Methods

A retrospective review of intravascular (arterial and venous) lesions involving the hand was conducted. Data regarding clinicopathologic findings were analyzed.

Results

We identified 10 patients with intravascular lesions of their hands including thromboemboli (n = 3), reactive intravascular conditions such as papillary endothelial hyperplasia or Masson's tumor (n = 2) and fasciitis (n = 1), as well as vascular neoplasms including pyogenic granuloma (n = 2) and angioleiomyoma (n = 2).

Conclusion

Blood vessel injury and/or venous thrombosis may predispose to several intravascular lesions of the hand. Recognition of reactive entities from neoplastic conditions is important.     

Therapeutic Efficacy of a Subunit Vaccine in Controlling Chronic Trypanosoma cruzi Infection and Chagas Disease Is Enhanced by Glutathione Peroxidase Over-Expression

Trypanosoma cruzi-induced oxidative and inflammatory responses are implicated in chagasic cardiomyopathy. In this study, we examined the therapeutic utility of a subunit vaccine against T. cruzi and determined if glutathione peroxidase (GPx1, antioxidant) protects the heart from chagasic pathogenesis. C57BL/6 mice (wild-type (WT) and GPx1 transgenic (GPx^tg) were infected with T. cruzi and at 45 days post-infection (dpi), immunized with TcG2/TcG4 vaccine delivered by a DNA-prime/Protein-boost (D/P) approach. The plasma and tissue-sections were analyzed on 150 dpi for parasite burden, inflammatory and oxidative stress markers, inflammatory infiltrate and fibrosis. WT mice infected with T. cruzi had significantly more blood and tissue parasite burden compared with infected/GPx^tg mice (n = 5-8, p<0.01). Therapeutic vaccination provided >15-fold reduction in blood and tissue parasites in both WT and GPx^tg mice. The increase in plasma levels of myeloperoxidase (MPO, 24.7%) and nitrite (iNOS activity, 45%) was associated with myocardial increase in oxidant levels (3-4-fold) and non-responsive antioxidant status in chagasic/WT mice; and these responses were not controlled after vaccination (n = 5-7). The GPx^tg mice were better equipped than the WT mice in controlling T. cruzi-induced inflammatory and oxidative stress markers. Extensive myocardial and skeletal tissue inflammation noted in chagasic/WT mice, was significantly more compared with chagasic/GPx^tg mice (n = 4-6, p<0.05). Vaccination was equally effective in reducing the chronic inflammatory infiltrate in the heart and skeletal tissue of infected WT and GPx^tg mice (n = 6, p<0.05). Hypertrophy (increased BNP and ANP mRNA) and fibrosis (increased collagen) of the heart were extensively present in chronically-infected WT and GPx^tg mice and notably decreased after therapeutic vaccination. We conclude the therapeutic delivery of D/P vaccine was effective in arresting the chronic parasite persistence and chagasic pathology; and GPx1 over-expression provided additive benefits in reducing the parasite burden, inflammatory/oxidative stress and cardiac remodeling in Chagas disease.     

Body condition is associated with a shorter breeding season and reduced ovulation rate in subtropical goats

To determine the effect of body condition on the characteristics of the breeding season in female goats from subtropical Mexico, does in either greater- or lesser-body condition (n=20/group) were monitored for the expression of estrous behavior, ovulation and ovulation rate between June and April. The commencement of estrus and ovulation occurred earlier (P<0.05) in does in greater than lesser body condition. The cessation of estrus and ovulation was later (P<0.05) in female goats with greater than those with lesser body condition. Does in greater body condition had more (P<0.001) normal estrous cycles than those in lesser body condition. As consequence, does from the greater body condition group had fewer short (P<0.001) or long (P<0.05) estrous cycles than those of in the lesser body condition group. The ovulation rate was greater (P<0.01) in the greater (1.9+/-0.1) than lesser body condition does (1.6+/-0.1). In conclusion, female goats in lesser body condition have a shorter breeding season, more abnormal estrous cycles, and fewer ovulations than does in greater body condition.     

Effect of extracellular matrix on adhesion, viability, actin cytoskeleton and K+ currents of cells expressing human ether à go-go channels

Ether à go-go (EAG) potassium channels possess oncogenic properties and have gained great interest as research tools for cancer detection and therapy. Besides, EAG electrophysiological properties are regulated through the cell cycle and determined by cytoskeletal interactions. Thus, because of the pivotal role of extracellular matrix (ECM) and cytoskeleton in cancer progression, we studied the effect of ECM components on adhesion, viability, actin organization and EAG currents in wild-type CHO cells (CHO-wt) and cells expressing human EAG channels (CHO-hEAG). At short incubation times, adhesion and viability of CHO-hEAG cells grown on collagen, heparin or poly-lysine were lower than CHO-wt cells, however, only CHO-hEAG sustained growing under total serum starvation. CHO-hEAG cells grown on poly-lysine did not organize their cytoskeleton but when grown on collagen or fibronectin displayed lamellipodia and stress fibers, respectively. Interestingly, EAG expressing cells displayed special actin structures suggesting a dynamic actin cytoskeleton, such structures were not exhibited by wild-type cells. EAG current density was significantly lower in cells grown on collagen at short incubation times. Finally, we studied potential associations between hEAG channels and integrins or actin filaments by confocal microscopy. No association between beta1-integrins and hEAG channels was found, however, a very strong co-localization was observed between hEAG channels and actin filaments, supported by immunoblot experiments in which hEAG channels were found in the insoluble fraction (associated to cytoskeleton). Our results suggest ECM components as potential modulators of oncogenic human-EAG expressing cells and emphasize the relationship between potassium channels, cytoskeleton, ECM and cancer.     

Conserved residues of the Pro103–Arg115 loop are involved in triggering the allosteric response of the Escherichia coli ADP-glucose pyrophosphorylase

The synthesis of glycogen in bacteria and starch in plants is allosterically controlled by the production of ADP-glucose by ADP-glucose pyrophosphorylase. Using computational studies, site-directed mutagenesis, and kinetic characterization, we found a critical region for transmitting the allosteric signal in the Escherichia coli ADP-glucose pyrophosphorylase. Molecular dynamics simulations and structural comparisons with other ADP-glucose pyrophosphorylases provided information to hypothesize that a Pro103–Arg115 loop is part of an activation path. It had strongly correlated movements with regions of the enzyme associated with regulation and ATP binding, and a network analysis showed that the optimal network pathways linking ATP and the activator binding Lys39 mainly involved residues of this loop. This hypothesis was biochemically tested by mutagenesis. We found that several alanine mutants of the Pro103–Arg115 loop had altered activation profiles for fructose-1,6-bisphosphate. Mutants P103A, Q106A, R107A, W113A, Y114A, and R115A had the most altered kinetic profiles, primarily characterized by a lack of response to fructose-1,6-bisphosphate. This loop is a distinct insertional element present only in allosterically regulated sugar nucleotide pyrophosphorylases that could have been acquired to build a triggering mechanism to link proto-allosteric and catalytic sites.     

Does morphology predict behavior? Correspondence between behavioral and morphometric data in a Tyrant‐flycatcher (Tyrannidae) assemblage in the Santa Marta Mountains,Colombia

ABSTRACT Morphology is commonly used as a predictor of ecological relationships among species when studying local assemblages of Neotropical birds. Nevertheless, most evidence supporting ecomorphological correspondence in birds comes from studies of communities and not from local assemblages and, moreover, from temperate latitudes. To increase our understanding of ecomorphological correspondence in Neotropical assemblages, we used three multivariate approaches to evaluate correspondence between morphological and foraging behavior data in a tyrant‐flycatcher assemblage (N= 12 species) in the Santa Marta Mountains in Colombia. Principal components analyses revealed similar species ordinations when using morphological measurements (beak size and shape, tarsus length, wing length, and tail length) or behavioral data (behavioral types of searching for prey and prey capture) separately. Discriminant function analyses tested the ability of morphological traits to predict foraging behavior, showing that more than 90% of all measured individuals (N= 267) were correctly classified in previously defined categories of search and attack behavior. Finally, Canonical correlation analyses revealed a significant correlation between morphological data and two independent datasets of search and attack behavior. Our results demonstrate that morphology can accurately predict ecology in an assemblage of Neotropical tyrannids, and similar results have been reported in previous studies of temperate Tyrant‐flycatchers. Our results also show that bill size and shape, wing length, and tarsus length are the best predictors of foraging behavior in this assemblage. Testing for ecomorphological correspondence in other Neotropical taxa would help identify subsets of phenotypic traits that could be used for a practical, but reliable, determination of ecological relationships within different assemblages.