Biology of chronic graft-versus-host disease: implications for a future therapeutic approach.

Hematopoietic cell transplantation (HCT) is frequently complicated by graft-versus-host disease (GVHD). During the past three decades, experimental studies and clinical observations have elucidated the pathophysiology of acute GVHD, but the biology of chronic GVHD is much less well understood. Recommendations of the NIH Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD have begun to standardize the diagnosis and clinical assessment of the disease. These criteria have emphasized the importance of qualitative differences, as opposed to time of onset after HCT, in making the distinction between acute and chronic GVHD. Experimental studies have generated at least four theories to explain the pathophysiology of chronic GVHD. These theories include 1) thymic damage and defective negative selection of T cells generated from marrow progenitors after HCT, 2) aberrant production of transforming growth factor-beta, 3) auto-antibody production, and 4) deficiency of T-regulatory cells. Recent studies in humans have corroborated a possible role for each of these mechanisms in humans. No animal model fully replicates all of the features of chronic GVHD in humans, and it appears likely that multiple biological mechanisms account for the diverse features the disease. Chronic GVHD may represent a "syndrome" with diverse causes among individual patients. In the future, it might become possible to tailor specific therapeutic interventions for patients as individually needed for each distinct pathophysiologic mechanism involved in development of the disease

Early Alteration of Nucleocytoplasmic Traffic Induced by Some RNA Viruses

AbstractA HeLa cell line expressing the green fluorescent protein fused to the SV40 T-antigen nuclear localization signal (EGFP-NLS) was established. Fluorescence in these cells was confined to the nuclei. After poliovirus infection, cytoplasmic fluorescence in a proportion of cells could be detected by 1 h postinfection (p.i.) and in virtually all of the fluorescent cells by 2 h p.i. The relocation could be prevented by cycloheximide but not by inhibition of poliovirus replication by guanidine · HCl. Nuclear exit of a protein composed of three copies of GFP fused to the NLS also occurred upon poliovirus infection. A similar redistribution of EGFP-NLS took place upon infection with coxsakievirus B3 and, to a lesser extent, with vesicular stomatitis virus. The EGFP-NLS efflux was not due to the loss of NLS. Thus, some positive-strand and negative-strand RNA viruses trigger a rapid nonspecific relocation of nuclear proteins

Lipid Regulators during Atherogenesis : expression of LXR, PPAR, and SREBP mRNA in the Human Aorta

Transcription factors LXRs, PPARs, and SREBPs have been implicated in a multitude of physiological and pathological processes including atherogenesis. However, little is known about the regulation of these transcription factors at different stages of atherosclerosis progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to compare the contents of mRNAs in pairs intact-injured aorta fragments taken from the same donors. Only minor changes in LXR?, LXR?, PPAR?, PPAR?, SREBP1, and SREBP2 mRNA levels were found in initial lesions as compared with intact non-diseased tissue. The contents of all mRNAs but SREBP2 mRNA were found to be progressively up-regulated in fatty streaks and fibrous lipoid plaques. These changes were only partially reproduced in cultured macrophages upon lipid loading. Wave-shaped changes in abundance of correlations between given group of mRNAs and 28 atherosclerosis-related mRNA species in the course of atherogenesis were observed. The impact of specific mRNA correlations on the total correlations also significantly varied between different lesion types. The study suggests that the extent and forms of LXR/PPAR/SREBP participation in intima functions vary nonlinear in individual fashion in atherogenesis. We speculate that the observed changes in mRNAs expression and coupling reflect shifts in lipid ligands availability and cellular composition in the course of atherosclerosis progression

Aplicación de la mejora continua al área de seguridad industrial y salud ocupacional para reducir los costos por accidentes laborales en la empresa Camposol S.A.

El autor no autorizó la publicación de la tesis

Using LoRa Networks in Automatic Band Dendrometer

В данной статье описывается опыт использования сетей передачи данных стандарта LoRa в автоматическом кольцевом дендрометре, разработанном собственными силами и описанном ранее [1]. Ранее нами был разработан и представлен автоматический кольцевой дендрометр с отправкой данных на сервер в интернете, был описан процесс создания прибора и результат его испытаний. В результате испытаний были сформулированы необходимые доработки, одной из которых была необходимость использовать для измерений сеть из нескольких датчиков, расположенных на одном участке, и передачу их измерений беспроводным способом на центральный дата логгер для обработки и передачи на сервер. Таким образом, появилась необходимость выбрать и внедрить энергосберегающий протокол обмена данными, обладающий достаточным радиусом действия и надежностью работы в условиях тайгиThis article describes the experience of using wireless LoRa data transfer in an automatic band dendrometer, developed by the author early [1]. Previously was developed an automatic band dendrometer with web data storage, we provided information about the process of creating the device and the result of its testing. As the result of the tests, the necessary improvements were formulated, one of which was the need to use a network of several sensors located in one area for measurements and transmit their measurements wirelessly to a central data logger for processing and transmission to the web server. Thus, it became necessary to select and implement an energy-saving data exchange protocol with a sufficient range and reliable performance in a taig

Changes of lysosomes in the earliest stages of the development of atherosclerosis

One of hypotheses of atherosclerosis is based on a presumption that the zones prone to the development of atherosclerosis contain lysosomes which are characterized by enzyme deficiency and thus, are unable to dispose of lipoproteins. The present study was undertaken to investigate the characteristics and changes of lysosomes in the earliest stages of the development of atherosclerosis. Electron microscopic immunocytochemistry revealed that there were certain changes in the distribution of CD68 antigen in lysosomes along the 'normal intima-initial lesion-fatty streak' sequence. There were no significant changes found in the key mRNAs encoding for the components of endosome/lysosome compartment in initial atherosclerotic lesions, but in fatty streaks, the contents of EEA1 and Rab5a mRNAs were found to be diminished while the contents of CD68 and p62 mRNAs were increased, compared with the intact tissue. The study reinforces a view that changes occurring in lysosomes play a role in atherogenesis from the very earlier stages of the disease

Regulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces

SummaryThe regulatory T (Treg) cells restrain immune responses through suppressor-function elaboration that is dependent upon expression of the transcription factor Foxp3. Despite a critical role for Treg cells in maintaining lympho-myeloid homeostasis, it remains unclear whether a single mechanism or multiple mechanisms of Treg cell-mediated suppression are operating in vivo and how redundant such mechanisms might be. Here we addressed these questions by examining the role of the immunomodulatory cytokine IL-10 in Treg cell-mediated suppression. Analyses of mice in which the Treg cell-specific ablation of a conditional IL-10 allele was induced by Cre recombinase knocked into the Foxp3 gene locus showed that although IL-10 production by Treg cells was not required for the control of systemic autoimmunity, it was essential for keeping immune responses in check at environmental interfaces such as the colon and lungs. Our study suggests that Treg cells utilize multiple means to limit immune responses. Furthermore, these mechanisms are likely to be nonredundant, in that a distinct suppressor mechanism most likely plays a prominent and identifiable role at a particular tissue and inflammatory setting

Microdissection and sequence analysis of pericentric heterochromatin from the Drosophila melanogaster mutant Suppressor of Underreplication

In the Suppressor of Underreplication (SuUR) mutant strain of Drosophila melanogaster, the heterochromatin of polytene chromosomes is not underreplicated and, as a consequence, a number of P-heterochromatic regions acquire a banded structure. The chromocenter does not form in these polytene chromosomes, and heterochromatic regions, normally part of the chromocenter, become accessible to cytological analysis. We generated four genomic DNA libraries from specific heterochromatic regions by microdissection of polytene chromosomes. In situ hybridization of individual libraries onto SuUR polytene chromosomes shows that repetitive DNA sequences spread into the neighboring euchromatic regions. This observation allows the localization of eu-heterochromatin transition zones on polytene chromosomes. We find that genomic scaffolds from the eu-heterochromatin transition zones are enriched in repetitive DNA sequences homologous to those flanking the suppressor of forked gene [su(f) repeat]. We isolated and sequenced about 300 clones from the heterochromatic DNA libraries obtained. Most of the clones contain repetitive DNA sequences; however, some of the clones have unique DNA sequences shared with parts of unmapped genomic scaffolds. Hybridization of these clones onto SuUR polytene chromosomes allowed us to assign the cytological localizations of the corresponding genomic scaffolds within heterochromatin. Our results demonstrate that the SuUR mutant renders possible the mapping of heterochromatic scaffolds on polytene chromosomes