Caracterización clínico-radiológica de pacientes con enfermedad pulmonar intersticial y panel de miositis positivo en hospital Santiago Oriente / Clinical-radiological characterization of patients with interstitial lung disease and positive myositis panel at hospital Santiago Oriente

Introducción: Las Enfermedades Pulmonares Intersticiales (EPI) afectan principalmente al intersticio pulmonar, con importante morbimortalidad asociada. Tienen un espectro de posibles etiologías que es cada vez más amplio. Hay una importante causalidad a partir de Enfermedades del Tejido Conectivo (ETC), describiéndose cada vez más casos asociados a Síndrome Antisintetasa, y con diversos patrones radiológicos según serología obtenida, agrupada en "Panel de Miositis" (PaM). El presente estudio de cohorte retrospectiva reúne PaMs realizados en el Hospital Santiago Oriente, correlacionando resultados con manifestaciones clínicas e imagenológicas. Material y Métodos: Se recuperaron 33 PaMs realizados entre 2017 y 2022, y a través de revisión de fichas de los pacientes de quienes provenían las PaMs se consignaron las principales manifestaciones clínicas, imagenológicas y de la serología reumatológica complementaria, estableciendo correlaciones entre múltiples variables. Resultados: Hubo 15 pacientes PaM positivos (45,4%), 8 de ellos (53%) ya contaban con alguna miopatía inflamatoria diagnosticada. Los principales hallazgos clínicos consignados fueron pápulas de Gottron, artritis, eritema heliotropo, Fenómeno de Raynaud y fiebre. El anticuerpo positivo más frecuente fue Ro-52. Se pudo objetivar ANA positivo en 10 casos (66,7%). Se identificó EPI en 66,7% de aquellos con PaM positivo, siendo la Neumonía Intersticial no específica fibrótica con Neumonía en Organización la manifestación más frecuente. No hubo asociación significativa entre manifestaciones imagenológicas y anticuerpos específicos. Se encontró ANA 1/80 en 66,7% de los casos, lo cual no se asoció a mayor riesgo de EPI. Conclusiones: Existe asociación entre varias ETC y las EPI. Destaca la importancia de los hallazgos clínicos para establecer un adecuado índice de sospecha, para dirigir oportunamente el estudio complementario (ej: PaM), y la eventual terapia específica.

Introduction: Interstitial Lung Diseases (ILD) mainly affect the pulmonary interstitium, with significant associated morbidity and mortality. They have a spectrum of possible etiologies that is increasingly broad. There is an important causality from Connective Tissue Diseases (CTD), describing more and more cases associated with Antisynthetase Syndrome, and with different radiological patterns according to the serology obtained, enclosed into "Panel of Myositis" (PaM). This retrospective cohort study gathers PaMs performed at Hospital Santiago Oriente, PaM results are correlated with clinical and imaging manifestations. Material and Methods: 33 PaMs performed between 2017 and 2022 were saved up and by reviewing the clinical records of the patients from whom the PaMs came, their clinical and radiological manifestations and the results of their complementary rheumatological serology were recorded to establish correlations between multiple variables. Results: There were 15 positive PaMs (45.4%), 8 (53%) of them already had some diagnosed inflammatory myopathy. The main clinical findings reported were Gottron's papules, arthritis, heliotrope erythema, Raynaud's phenomenon, and fever. The most frequent positive antibody detected was Ro-52. Positive ANA could be found in 10 cases (66.7%). PID was identified in 66.7% of those with a positive PaM, being non-specific fibrotic Interstitial Pneumonia with Organizing Pneumonia being the most frequent manifestation. There was no significant association between imaging manifestations and specific antibodies. ANA 1/80 was found in 6.7% of the cases, which was not associated with an increased risk of PID. Conclusions: There is association between several CTEs and EPIs. It is necessary to highlight the importance of the clinical findings to establish an adequate index of suspicion, in order to timely direct the complementary study (eg: PaM), and the eventual specific therapy.

Mutations in aminoacyl-tRNA synthetase genes: an analysis of 10 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of the diseases associated with aminoacyl-tRNA synthetases (ARS) deficiency.@*METHODS@#A retrospective analysis was performed of the clinical and gene mutation data of 10 children who were diagnosed with ARS gene mutations, based on next-generation sequencing from January 2016 to October 2019.@*RESULTS@#The age of onset ranged from 0 to 9 years among the 10 children. Convulsion was the most common initial symptom (7 children). Clinical manifestations included ataxia and normal or mildly retarded intellectual development (with or without epilepsy; n=4) and onset of epilepsy in childhood with developmental regression later (n=2). Some children experienced disease onset in the neonatal period and had severe epileptic encephalopathy, with myoclonus, generalized tonic-clonic seizure, and convulsive seizure (n=4); 3 had severe delayed development, 2 had feeding difficulty, and 1 had hearing impairment. Mutations were found in five genes: 3 had novel mutations in the AARS2 gene (c.331G>C, c.2682+5G>A, c.2164C>T, and c.761G>A), 2 had known mutations in the DARS2 gene (c.228-16C>A and c.536G>A), 1 had novel mutations in the CARS2 gene (c.1036C>T and c.323T>G), 1 had novel mutations in the RARS2 gene (c.1210A>G and c.622C>T), and 3 had novel mutations in the AARS gene (c.1901T>A, c.229C>T, c.244C>T, c.961G>C, c.2248C>T, and Chr16:70298860-70316687del).@*CONCLUSIONS@#A high heterogeneity is observed in the clinical phenotypes of the diseases associated with the ARS deficiency. A total of 14 novel mutations in 5 genes are reported in this study, which enriches the clinical phenotypes and genotypes of the diseases associated with ARS deficiency.

The role and mechanism of leucyl-tRNA synthetase in the regulation of protein synthesis in aging skeletal muscle / 生理学报

The imbalance of protein metabolism is the major cause of skeletal muscle atrophy, and the decrease of protein synthesis directly leads to the occurrence and development of age-related sarcopenia. The canonical role of leucyl-tRNA synthetase (LeuRS) is ligating leucine to the cognate tRNA, and thus it plays a central role in genetic coding. With the further studies of LeuRS in recent years, LeuRS has been found to control protein homeostasis in aging skeletal muscle via its non-canonical role. In this paper, we reviewed the structure and biological features of aminoacyl-tRNA synthetase and LeuRS, and summarized the recent advances in studies on the effects of LeuRS in regulating aging skeletal muscle protein synthesis as an intracellular leucine sensor. Moreover, we also analyzed the potential role of LeuRS in activation of mammalian target of rapamycin complex 1 (mTORC1) signaling transduction pathway in response to anabolic stimuli such as exercise and amino acids ingestion. This paper may provide some new ideas for the prevention, diagnosis and treatment of age-related sarcopenia.

Unnatural amino acid orthogonal translation: a genetic engineering technology for the development of new-type live viral vaccine / 生物工程学报

Unnatural amino acid orthogonal translation machinery can insert unnatural amino acids at desired sites of protein through stop codon by means of foreign orthogonal translation system composed of aminoacyl-tRNA synthetase and orthogonal tRNA genes. This new genetic engineering technology is not only a new tool for biochemical researches of proteins, but also an epoch-making technology for the development of new-type live viral vaccines. The mutated virus containing premature termination codon in genes necessary for replication can be propagated in transgenic cells harboring unnatural amino acid orthogonal translation machinery in media with corresponding unnatural amino acid, but it cannot replicate in conventional host cells. This replication-deficient virus is a new-type of live viral vaccine that possesses advantages of high efficacy of traditional attenuated vaccine and high safety of killed vaccine. This article reviews the application and prospect of unnatural amino acid orthogonal translation machinery in the development of novel replication-deficient virus vaccines.

Methionyl-tRNA Synthetase is a Useful Diagnostic Marker for Lymph Node Metastasis in Non-Small Cell Lung Cancer

PURPOSE: Identification of lymph node (LN) metastasis in non-small cell lung cancer (NSCLC) is critical for disease staging and selection of therapeutic modalities. Sometimes it is not possible to obtain LN core tissue by endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA), resulting in low diagnostic yield. MATERIALS AND METHODS: In this study, 138 specimens were collected from 108 patients who underwent EBUS-TBNA under the suspicion of LN metastasis of NSCLC. Diagnostic yields of anti-CD45 and anti-methionyl-tRNA synthetase (MRS), immunofluorescent (IF) staining on cytology specimens were compared with those of conventional cytology and positron emission tomography-computed tomography (PET-CT). RESULTS: MRS was strongly expressed in NSCLC cells metastasized to LNs, but weakly expressed in cells at the periphery of the LN germinal center. The majority of cells were CD20 positive, although a few cells were either CD3 or CD14 positive, indicating that CD45 staining is required for discrimination of non-malignant LN constituent cells from NSCLC cells. When the diagnostic efficacy of MRS/CD45 IF staining was evaluated using 138 LN cellular aspirates from 108 patients through EBUS-TBNA, the sensitivity was 76.7% and specificity was 90.8%, whereas those of conventional cytology test were 71.8% and 100.0%, respectively. Combining the results of conventional cytology testing and those of PET-CT showed a sensitivity and specificity of 71.6% and 100%, and the addition of MRS/CD45 dual IF data to this combination increased sensitivity and specificity to 85.1% and 97.8%, respectively. CONCLUSION: MRS/CD45 dual IF staining showed good diagnostic performance and may be a good tool complementing conventional cytology test for determining LN metastasis of NSCLC.

Profil épidémiologique, clinique et valeur diagnostique des anticorps anti-Jo1 (anticorps anti-aminoacyl-t-RNA-synthétases). Etude rétrospective à propos d'une série de 22 patients

Propos : Notre objectif était de rapporter les caractéristiques épidémiologiques et cliniques de 22 patients avec anticorps anti-Jo1 positifs.Patients et méthodes : Etude rétrospective menée dans les services de Médecine interne et d'immunologie (Sfax-Tunisie) entre 2010 et 2016. Le dépistage des Anticorps Anti-Nucléaires (AAN) était réalisé par Immuno-Fluorescence Indirecte (IFI) sur cellules Hep2. Chaque sérum positif était testé par immunodot. Résultats : Vingt-deux patients ont été étudiés : 18 femmes et 4 hommes (âge moyen : 46 ans). Les principales manifestations cliniques étaient les signes rhumatologiques : 14 cas (63%), les signes généraux : 11 cas (50%), les manifestations musculaires : 8 cas (36%), les signes pleuro-pulmonaires : 8 cas (36%), les signes cutanés : 9 cas (45%), un phénomène de Raynaud : 2 cas (9%) et des mains de mécaniciens : 2 cas (9%). Le diagnostic d'une myosite de chevauchement était retenu chez 6 patients dont 4 avaient un Syndrome des Anti-Synthétases (SAS). Le diagnostic de maladies auto-immunes ou systémiques était retenu chez 9 malades. Le diagnostic de maladie non auto-immune était établi chez 7 patients. Tous les patients avaient des anti-Jo1 positifs associés avec l'anti- Ro52 (11 cas), l'anti-SSA (7 cas), l'anti-SSB (17 cas), l'anti-Sm (2 cas), l'anti-AND (1 cas), l'anti-centromère (3 cas) et l'anti Scl-70 (3 cas). Conclusion : Notre étude montre la rare prévalence des anticorps anti-Jo1, suggère l'intérêt de les rechercher devant un contexte évocateur et de façon systématique en cas de myosite ou d'atteinte pulmonaire interstitielle ou de fluorescence cytoplasmique des AAN

Doença pulmonar intersticial relacionada a miosite e a síndrome antissintetase / Myositis-related interstitial lung disease and antisynthetase syndrome

Em pacientes com miosite, é comum o comprometimento pulmonar, e a presença de anticorpos anti-aminoacil-RNAt sintetase (anti-ARS) é preditora da presença ou do desenvolvimento de doença pulmonar intersticial (DPI). Uma entidade clínica distinta - a síndrome antissintetase - é caracterizada pela presença de anticorpos anti-ARS, miosite, DPI, artrite, fenômeno de Raynaud e "mãos de mecânico". O mais comum anticorpo anti-ARS é o anti-Jo-1. Anticorpos anti-ARS mais recentemente descritos podem conferir um fenótipo que é distinto daquele de pacientes com positividade para anti-Jo-1, sendo caracterizado por uma menor incidência de miosite e uma maior incidência de DPI. Nos pacientes com DPI relacionada à síndrome antissintetase, a resposta a medicações imunossupressoras é em geral favorável.

In patients with myositis, the lung is commonly involved, and the presence of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies marks the presence or predicts the development of interstitial lung disease (ILD). A distinct clinical entity-antisynthetase syndrome-is characterized by the presence of anti-ARS antibodies, myositis, ILD, fever, arthritis, Raynaud's phenomenon, and mechanic's hands. The most common anti-ARS antibody is anti-Jo-1. More recently described anti-ARS antibodies might confer a phenotype that is distinct from that of anti-Jo-1-positive patients and is characterized by a lower incidence of myositis and a higher incidence of ILD. Among patients with antisynthetase syndrome-related ILD, the response to immunosuppressive medications is generally, but not universally, favorable.

Frameshift Mutation of MARS Gene Encoding an Aminoacyl-tRNA Synthetase in Gastric and Colorectal Carcinomas with Microsatellite Instability

No abstract available.

A Case of Dermatomyositis with Secondary Organizing Pneumonia / 영남의대학술지

Dermatomyositis is characterized by progressive, symmetric, proximal muscle weakness and a nonsuppurative inflammatory myopathy of unknown etiology involving predominantly skeletal muscles. It is also characterized by typical skin lesions. Interstitial lung disease has a poor prognosis when it is associated with dermatomyositis. Organizing pneumonia is a disease in which granulation tissue fills the lumina of terminal and respiratory bronchioles and extends into the distal airspaces. The cryptogenic nature of the process is appreciated in that organizing pneumonia patterns of injury can be seen in secondary forms of the disease (secondary organizing pneumonia). Organizing pneumonia has been reported to occur in 5~10% in dermatomyositis-polymyositis patients. Anti-histidyl tRNA synthetase antibody (anti-Jo-1) is a predictive disease marker that is reported to occur in up to 70% of patients. We describe a 49-year-old male dermatomyositis patient who presented with organizing pneumonia and was found to have negative anti-Jo-1 antibody.

A scenario on the stepwise evolution of the genetic code / 基因组蛋白质组与生物信息学报·英文版

It is believed that in the RNA world the operational (ribozymes) and the informational (riboscripts) RNA molecules were created with only three (adenosine, uridine, and guanosine) and two (adenosine and uridine) nucleosides, respectively, so that the genetic code started uncomplicated. Ribozymes subsequently evolved to be able to cut and paste themselves and riboscripts were acceptive to rigorous editing (adenosine to inosine); the intensive diversification of RNA molecules shaped novel cellular machineries that are capable of polymerizing amino acids-a new type of cellular building materials for life. Initially, the genetic code, encoding seven amino acids, was created only to distinguish purine and pyrimidine; it was later expanded in a stepwise way to encode 12, 15, and 20 amino acids through the relief of guanine from its roles as operational signals and through the recruitment of cytosine. Therefore, the maturation of the genetic code also coincided with (1) the departure of aminoacyl-tRNA synthetases (AARSs) from the primordial translation machinery, (2) the replacement of informational RNA by DNA, and (3) the co-evolution of AARSs and their cognate tRNAs. This model predicts gradual replacements of RNA-made molecular mechanisms, cellular processes by proteins, and informational exploitation by DNA.

Calcium regulates the expression of a Dictyostelium discoideum asparaginyl tRNA synthetase gene.

In a screen for calcium-regulated gene expression during growth and development of Dictyostelium discoideum we have identified an asparaginyl tRNA synthetase (ddAsnRS) gene, the second tRNA synthetase gene identified in this organism. The ddAsnRS gene shows many unique features. One, it is repressed by lowering cellular calcium, making it the first known calcium-regulated tRNA synthetase. Two, despite the calcium-dependence, its expression is unaltered during the cell cycle, making this the first D. discoideum gene to show a calcium-dependent but cell cycle phase-independent expression. Finally, the N-terminal domain of the predicted ddAsnRS protein shows higher sequence similarity to Glutaminyl tRNA synthetases than to other Asn tRNA synthetases. These unique features of the AsnRS from this primitive eukaryote not only point to a novel mechanism regulating the components of translation machinery and gene expression by calcium, but also hint at a link between the evolution of GlnRS and AsnRS in eukaryotes.

Regulation, characterization and factors affecting the amino acid transport systems

En esta revisión se describen los diferentes sistemas de transporte para aminoácidos, la caracterización de éstos y de sus componentes, los factores que afectan las características cinéticas de los acarreadores específicos de los sistemas de transporte, y la importancia del transporte de aminoácidos en el mantenimiento de las concentraciones plasmáticas e intracelulares de aminoácidos en diversos tejidos, así como su papel en el control del metabolismo de aminoácidos.

Isolation and characterization of an analogue-resistant aminoacyl-tRNA synthetase mutant in Aspergillus nidulans.

Six mutants resistant to p-fluorophenylalanine (FPA) were selected on a medium containing aspartate as the sole source of nitrogen using a phenylalanine-requiring (phenA)auxotroph of A. nidulans as the wild type. The mutants, on the basis of genetic characterization, were found to be alleilic and located on the left arm of the linkage group III, approximately 13 map unit left to meth H locus, henceforth assigned to the symbol fpaV. At a fixed concentration of phenylalanine (23 micrograms/ml), the LD50 value of FPA for all the six mutants was found to be about three times more than that for the wild type strain. Affinity chromatographic purification of the enzyme phenylalanyl-tRNA (Phe-tRNA) synthetase from the mutant as well as the wild type strains, revealed that the wild type enzyme had about 1.4-fold higher affinity for phenylalanine as compared to that for FPA, both in the affinity column and in the catalytic reaction. However, the mutant enzyme showed almost a similar affinity for both in columns but a greatly reduced affinity for FPA in the catalytic reaction.

Threonyl-tRNA synthetase from bovine liver: purification and kinetic properties in the ATP-pyrophosphate exchange reaction

Treonil-RNA sintetase (E.C. 6.1.1.3) foi purificada quase à homogeneidade de fígado bovino cerca de 500 vezes com um rendimento de 48%. Duas bandas de pesos moleculares 90.000 e 82.000, respectivamente, foram obtidas por eletroforese em gel em presença de dodecil sulfato de sódio. A enzima tem um ponto isoelétrico de 5,2 por eletroforese em gel de poliacrilamida contendo anfoline. Utilizando-se a reaçäo de intercâmbio ATP-PPi foram determinadas as condiçöes ótimas de ensaio e os valores aparentes de Km. através da mesma reaçäo foram também observados efeitos de cátions divalentes e diaminas em substituiçäo ao Mg2+ e efeitos de reagentes sulfidrílicos