Pseudomembranous Aspergillus tracheobronchitis in a heart transplant recipient

A. Ramos, J. Segovia, M. Gómez-Bueno, C. Salas, M.T. Lázaro, I. Sanchez, L. Pulpón. Pseudomembranous Aspergillus tracheobronchitis in a heart transplant recipient.
Transpl Infect Dis 2010: 12: 60–63. All rights reserved
Abstract: Aspergillus tracheobronchitis (AT) is an uncommon clinical presentation of pulmonary aspergillosis that frequently progresses to invasive pulmonary aspergillosis. Diagnosis of AT may be delayed because of its insidious onset, non-specific signs and symptoms, and scarcity of radiographic abnormalities. We report the case of a patient who received a heart transplant (HT) because of cardiac amyloidosis and who developed pseudomembranous AT. Possible risk factors concurrent in this case were splenectomy, lymphocytopenia, and previous cytomegalovirus infection. Chest computed tomography scan showed thickening of the left bronchi and a 'tree-in-bud' pattern with multiple small nodules. Bronchoscopic examination revealed raised yellowish pseudomembranous plaques on the tracheobronchial tree. Bronchoalveolar lavage and aspirate cultures yielded Aspergillus fumigatus . The patient recovered with voriconazole. Clinicians should be aware of AT as a potential cause of respiratory symptoms with few radiographic abnormalities in HT recipients, as delay in performing bronchoscopy could result in an unfavorable prognosis.     

Matrix metalloproteinase‐9‐mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

Background: During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP‐9, increase significantly. MMPs play major roles in ECM remodelling, via their activity in the proteolytic degradation of extracellular macromolecules such as collagens, resulting in the generation of specific cleavage fragments. These neo‐epitopes may be used as markers of fibrosis. Aims: The current study investigated whether a novel enzyme‐linked immunosorbent assay (ELISA) assay specifically measuring an MMP‐9‐cleaved sequence of type III collagen located at position 610 (CO3‐610C) may be used as a marker of liver fibrosis. Material and methods: Bile duct ligation (BDL) was performed in 20 rats, with sham operations performed on another 20 rats. Serum levels of the neo‐epitope CO3‐610C (MMP‐mediated type III collagen degradation) were determined with an ELISA at 14 and 28 days post‐surgery. Liver fibrosis was evaluated by quantitative digital image analysis of Sirius red‐stained formalin‐fixed and paraffin‐embedded sections. Western blot and densitometry were performed to confirm the CO3‐610C ELISA data. Results: CO3‐610C levels in serum increased significantly in BDL rats compared with those undergoing sham operations (% increase: 14 days=153%, P<0.0001; 28 days=134%, P=0.0014). This increase was confirmed by Western blot and densitometry of the identified bands. The CO3‐610C levels correlated to liver fibrosis (R²=0.23 and P=0.01), as evaluated by quantitative digital histology. Discussion and conclusion: The data suggest that MMP‐9‐mediated CO3 turnover is a central event in the pathogenesis of fibrosis, and that the neo‐epitope generated may be a novel biochemical marker.     

Innate immune response in the hemolymph of an ascidian, Halocynthia roretzi, showing soft tunic syndrome, using label-free quantitative proteomics

Soft tunic syndrome of Halocynthia roretzi manifests as soft, weak, and rupturable tunics, causing mass mortality. Utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS), innate immune response was established by comparing hemolymph protein profiles of ascidians with healthy or softened tunics. Of 100 proteins in each individual ascidian, 59 proteins from healthy and 56 proteins from diseased ascidians were functionally classified. Proteins found only in diseased individuals included trypsin inhibitor and Hr-29, and with high exponentially modified protein abundance index (emPAI) values. From 41 proteins identified to be common to both healthy and diseased ascidians, 15 were associated with innate immune response. Ficolin 3, a component of the lectin-complement system, was significantly decreased in diseased ascidians, but a cell surface protein, type II transmembrane serine protease-1 (TTSP), was considerably elevated. These results suggest that trypsin inhibitor, ficolin 3, and TTSP are probably involved in the innate immune response related to this tunic disease. Beside, Hr-29 could be suggested as a biomarker for soft tunic syndrome.     

Stress, prefrontal cortex and environmental enrichment: studies on dopamine and acetylcholine release and working memory performance in rats

The aim of the present study was to investigate whether environmental enrichment changes the effects of acute stress on both the release of dopamine and acetylcholine in the prefrontal cortex (PFC) and working memory performance. Male Wistar rats (3 months of age) were housed in enriched or control conditions during 12 months. Behavioural testing was carried out to assess working memory performance in a delayed alternation task (water escape T-maze). Horizontal and vertical motor activity were also monitored in the open field. After behavioural testing (open field and water T-maze), animals were implanted with guide cannula in the PFC to perform microdialysis experiments and to monitor dopamine and acetylcholine extracellular concentrations. Handling stress (40min) produced similar increases of extracellular concentrations of dopamine in the PFC of both enriched and control animals. In contrast, handling stress increased significantly the extracellular concentrations of acetylcholine in the PFC of control, but not enriched, animals. Exposing animals to a lit open field during 10min significantly reduced working memory performance assessed immediately in the water T-maze just in control animals, though these effects were not significantly different between both groups of animals. Spontaneous motor activity in the open field was lower in enriched compared to control animals. These results suggest that environmental enrichment changes acetylcholine, but not dopamine, reactivity to stress in the PFC.     

Selective protection against oxidative damage in brain of mice with a targeted disruption of the neuronal nitric oxide synthase gene

Nitric oxide (NO) is an essential messenger molecule in brain, where it is produced in neurons mostly by the activity of the neuronal isoform of nitric oxide synthase (nNOS). To understand the participation of the different isoforms of NOS in physiological functioning and in pathological processes, mice with null mutations for each of the NOS isoforms have been generated. In the present paper, we report that there is a selective protection from oxidative damage in the brain of mice with a targeted disruption of the nNOS gene. The cerebellum of these mice shows reduced levels of lipid peroxidation (LP) at the different ages tested, compared with wild-type mice, and also a reduction in the formation of reactive oxygen species (ROS). We observed a decrease of LP in cortex, and no effect on either LP or ROS formation was observed in striatum of knockout mice compared with wild type. We also report increased spontaneous motor activity of knockout mice. The expression and activity of nNOS are crucial to maintain redox status in brain, and we consider that the alteration in oxidative damage may help us to explain the phenotypical characteristics of nNOS knockout mice and their differential susceptibility to brain insults.     

High-risk hypertrophic cardiomyopathy associated with a novel mutation in cardiac Myosin-binding protein C

Hypertrophic cardiomyopathy is an autosomal dominant inherited disease characterized by ventricular hypertrophy and myofibril disarray. Mutations responsible for hypertrophic cardiomyopathy have been identified in 11 genes that encode for cardiac sarcomere proteins. Traditionally, hypertrophic cardiomyopathy due to mutation of the myosin-binding protein C gene (MYBPC3) has been thought to follow a benign course. We report a family with several members affected by hypertrophic cardiomyopathy in which there was a high incidence of sudden death. Disease was presumably caused by the substitution of cytosine by guanine at nucleotide 269 of MYBPC3 mRNA. This mutation, which has not previously been described, modifies codon 79, which encodes for the incorporation of a tyrosine, and gives rise to a stop codon. The mutation described here appears to confer a higher risk than that previously associated with hypertrophic cardiomyopathy due to MYBPC3 gene mutation.     

SVM-based computer-aided diagnosis of the Alzheimer's disease using t-test NMSE feature selection with feature correlation weighting

This letter shows a computer-aided diagnosis (CAD) technique for the early detection of the Alzheimer's disease (AD) based on single photon emission computed tomography (SPECT) image feature selection and a statistical learning theory classifier. The challenge of the curse of dimensionality is addressed by reducing the large dimensionality of the input data and defining normalized mean squared error features over regions of interest (ROI) that are selected by a t-test feature selection with feature correlation weighting. Thus, normalized mean square error (NMSE) features of cubic blocks located in the temporo-parietal brain region yields peak accuracy values of 98.3% for almost linear kernel support vector machine (SVM) defined over the 20 most discriminative features extracted. This new method outperformed recent developed methods for early AD diagnosis.     

GABAergic neuron distribution in the pedunculopontine nucleus defines functional subterritories

γ‐Aminobutyric acid (GABA)ergic neurons are widely distributed in brainstem structures involved in the regulation of the sleep‐wake cycle, locomotion, and attention. These brainstem structures include the pedunculopontine nucleus (PPN), which is traditionally characterized by its population of cholinergic neurons that have local and wide‐ranging connections. The functional heterogeneity of the PPN is partially explained by the topographic distribution of cholinergic neurons, but such heterogeneity might also arise from the organization of other neuronal populations within the PPN. To understand whether a topographical organization is also maintained by GABAergic neurons, we labeled these neurons by in situ hybridization for glutamic acid decarboxylase mRNA combined with immunohistochemistry for choline acetyltransferase to reveal cholinergic neurons. We analyzed their distribution within the PPN by using a method to quantify regional differences based on stereological cell counts. We show that GABAergic neurons of the rat PPN have a rostrocaudal gradient that is opposite to that of cholinergic neurons. Indeed, GABAergic neurons are predominantly concentrated in the rostral PPN; in addition, they form, along with cholinergic neurons, a small, high‐density cluster in the most caudal portion of the nucleus. Thus, we provide evidence of heterogeneity in the distribution of different neuronal populations in the PPN and show that GABAergic and cholinergic neurons define neurochemically distinct areas. Our data suggest that the PPN is neurochemically segregated, and such differences define functional territories. J. Comp. Neurol. 515:397–408, 2009. © 2009 Wiley‐Liss, Inc.