ABSTRACT
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.
Subject(s)
Humans , Amino Acyl-tRNA Synthetases , Carcinoma, Non-Small-Cell Lung , Complement System Proteins , Discrimination, Psychological , Electrons , Germinal Center , Ligases , Lymph Nodes , Methionine-tRNA Ligase , Needles , Neoplasm Metastasis , Sensitivity and SpecificityABSTRACT
Objective To investigate the clinical,serological and imaging features of antisynthetase syndrome (ASS) patients with different positive anti-aminoacyl-tRNA synthase (ARS) antibodies.Methods The demographic characteristics,major clinical data,serological parameters,high resolution CT (HRCT) imaging features and pulmonary function characteristics in 60 cases of ASS [including 42 cases with positive anti-histidine tRNA synthetase (Jo-1) antibody,and 7 cases with positive anti-threonyl tRNA synthetase (PL-7) antibody,5 cases with positive anti-alanyl tRNA synthetase (PL-12) antibody,3 cases with positive anti-glycyl tRNA synthetase (E J) antibody and 3 cases with positive anti-leucyl tRNA synthetase (OJ) antibody] were collected.The differences in ASS patients with different positive ARS antibodies were analyzed by the x2 test and Fisher exact test.Results ① The ASS with different positive ARS antibodies was common in patients with DM/PM,[60％ (36/60),28％ (17/60)],and also appeared in patients with other connective tissue diseases,such as RA(5％,3/60),SS(3％,2/60),SLE(2％,1/60),etc.With ASS diagnosed,ILD complicated with myositis was the most common clinical features (63％,38/60).Typical clinical triad syndrome (myositis,ILD and arthritis) in 52％(31/60) patients,and myositis complicated with ILD,and mechanics hands accounted for 38％ (23/60) respectively.Some patients were complicated with isolated arthritis (25％,15/60),myositis (23％,14/60) and ILD (13％,8/60).The typical triad syndrome (myositis,ILD and arthritis) only accounted for 5％(3/60).The incidence of Jo-1,EJ and OJ antibodies [71％(30/42),100％(3/3),100％(3/3)] was significantly higher than that of PL-12 antibody (20％,1/5).There was a statistically significant difference (x2=5.263,P＜0.05;x2=4.8,P＜ 0.05;x2=4.8,P＜0.05).② The positive rate of ANA was 98％(59/60).Furthermore,the fluorescence staining model of anti-OJ antibody ANA was spotted,and the other subtypes were cytosolic.The positive rate of anti-SSA-52 antibody was 45％(27/60),and there was no statistical difference between the subtypes (P＞0.05).③ The ILD incidence of different positive antibodies had no significant difference in 82％ (49/60) ASS patients with ILD.The lung function in patients with ASS-ILD showed restrictive ventilation and diffused dysfunction.Grid shadow (76％,37/49) and grind glass (35％,17/49) were the most common signs of HRCT.Nonspecific interstitial pneumonia (NSIP) (78％,38/49) was the most common subtype of ILD.The incidence of traction bronchiectasis in ASS patients with PL-12 antibody (75％,3/4) was higher than that in ASS patients with Jo-1 antibody (22％,8/36).The incidence of pleural effusion in ASS patients with OJ antibody (100％,2/2) was significantly higher than that in ASS patients with Jo-1 antibody (17％,6/36).The incidence of pericardial effusion in ASS patients with PL-7 antibody (75％,3/4) was significantly higher than that in ASS patients with Jo-1 antibody (19.4％,7/36).All the differences were statistically significant (x2=5.26,P＜0.05).The ASS-ILD lung function indicated restrictive ventilatory function and diffusion dysfunction.④ There was no significant difference in clinical data,serological indicators,ILD imaging findings,interstitial lung types and lung function between Jo-1 antibody and non-Jo-1 antibody ASS patients (P＞0.05).Conclusion The ASS with different positive ARS antibodies is very common in patients with DM/PM,and is also observed in patients with other connective tissue diseases.ILD and myositis are the most common clinical features of ASS,followed by the typical triad syndrome (myositis,ILD and arthritis).Myositis is commonly observed in ASS patients with Jo-1,EJ and OJ antibodies,while is rarely observed in ASS patients with PL-12 antibody.The diagnosis of ASS should be alert to the onset of isolated arthritis or ILD.Anti-SSA-52 antibody may be related to ASS.NSIP is the most common HRCT pattern in ASS-ILD patients.There are some differences in signs among various subtypes,indicating that the difference of fibrosis in the lung and inflammatory reactions in the body being correlated with the ASS specificities.
ABSTRACT
Aminoacyl-tRNA synthetase catalyzing the first reaction of protein biosynthesis. In mammalian cells, eight aminoacyl-tRNA synthetases (aaRSs) and three auxiliary protein factors form a macromolecular aminoacyl-tRNA synthetases complex (aaRS complex). The three nonsynthetase protein factors, namely, p43, p38, and p18 were found to be involved in many other important life activities besides their roles in the complex. The auxiliary factor p43 was the precursor of endothelial monocyte activating polypeptideⅡ (EMAPⅡ), which involved in angiogenesis and apoptosis. The auxiliary factor p38 was crucial for the development of lung, and its abnormal accumulation in neuron would be related to the Parkinson’s disease. The auxiliary factor p38 and p18 could promote the repair of DNA damage via different pathways in a highly organized way. All these breakthroughs enhance our understanding about the interaction between the aaRS complex and the macromolecular signaling network and promote the studies on this field.
ABSTRACT
Aminoacyl-tRNA synthetase is a class of ancient proteins, catalyzing the first reaction of protein biosynthesis. It has been found that they also participate in a lot of other cellular processes such as editing, tRNA maturation and transfer, RNA cleavage and function as cellular factors. Recent studies showed that some mitochondrial aminoacyl-tRNA synthetases are closely related with human diseases. A single point mutation in intervening sequence 2 (IVS2) of human mitochondrial arginyl-tRNA synthetase gene causes abnormal cleavage of its transcript, resulting in pontocerebellar hypoplasia. A series of mutations in human mitochondrial aspartyl-tRNA synthetase gene cause rapid decay of its mRNA or alteration in protein primary sequence, leading to leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. A single nucleotide polymorphism in human mitochondrial leucyl-tRNA synthetase is significantly associated with type 2 diabetes. These results further enhance our understanding about the cellular function of aminoacyl-tRNA synthetase and promote studies toward the mechanism and therapy of aminoacyl-tRNA synthetase-causing mitochondrial diseases.
ABSTRACT
Aminoacyl-tRNA synthetases (AARSs) catalyze aminoacylation of their tRNAs for protein biosynthesis. As belong to one of the most ancient and conserved enzyme family their additional functions in mammalian cells were focused recently. Mutations in tyrosyl-tRNA synthetase, glycyl-tRNA synthetase and alanyl-tRNA synthetase from patients and mice models were identified to cause two subtypes of Charcot-Marie-Tooth disease and cerebellar Purkinje cell loss, respectively. These mutations affect different functions of the three enzymes including aminoacylation, editing and unknown functions. These results combined AARSs with neurodegeneration and gave new sights into neuropathy.
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Total tRNA was isolated, purified and quantitated from earthworm, cockroach, fresh water mussel and rat liver. The total tRNA content of invertebrates was found to be much lower than that of rat liver. When checked for aminoacylation capacity with homologous and heterologous enzymes and algal protein hydrolysate, the tRNA preparation from rat liver and fresh water mussel, a mollusc, were found to be active. On the other hand, the tRNAs from earthworm, an annelid, and cockroach, an arthropod, were completely inactive with the homologous enzymes but showed partial activity with heterologous enzymes. Similar results were obtained with individual amino acids also. The low activity or inactivity of earthworm and cockroach tRNAs appears to be due to certain endogenous aminoacylation inhibitors.
ABSTRACT
In the process of protein biosynthesis, an aminoacyl-tRNA synthetase strictly recognizes the cognate amino acid and tRNA species. Spectroscopic and biochemical analyses have been made of a heterologous system of Thermus thermophilus glutamyl-tRNA synthetase and Escherichia coli tRNAGlu. The conformational difference between the initial complex and active complex has been observed, which is probably related with the strict recognition of aminoacyl-tRNA synthetase. tRNA species are post-transcriptionally modified at specific sites. Two types of modified uridine nucleosides have been found in the first position of anticodon, namely 5-hydroxyuridine derivatives (xo5U) and 5-methyl-2-thiouridine derivatives (xm5s2U). From the analyses of nuclear magnetic resonance spectra, the conformational characteristics of the two types of modified uridine nucleotides have been found to be remarkably different from each other. The conformational flexibility of xo5U nucleotides allow the multiple recognition of codons, whereas the conformational rigidity of xm5s2U nucleotides guarantees the recognition of correct codons. The modification of uridines in the first position of anticodon contributes to the correct and efficient translations of codons in protein biosynthesis.