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OBJECTIVE: Anastomotic leakage is one of the most severe complications after esophagectomy. However, a diagnostic gold standard for anastomotic leakage has not been established yet. This retrospective cohort study aimed to evaluate the potential use of routine postoperative contrast-enhanced computed tomography findings as an early predictor of anastomotic leakage in patients who underwent esophagectomy for esophageal cancer. METHODS: This study included 75 patients who underwent Mckeown esophagectomy, of whom 22 developed anastomotic leakage after surgery. The computed tomography findings for this patient cohort were categorized into 3 grades based on mural enhancement patterns observed at the anastomotic site. Both semiquantitative and quantitative analyses were performed, and the interobserver agreement between the 2 experienced radiologists was assessed. RESULTS: It was found that poor enhancement in both the early and portal venous phases (grade 2) had a robust association with the occurrence of anastomotic leakage. The computed tomography enhancement ratio that is used to estimate wall degeneration and ischemia was significantly higher in patients with anastomotic leakage. CONCLUSIONS: Routine postoperative contrast-enhanced computed tomography could be beneficial for the early detection of anastomotic leakage, even in asymptomatic patients, after esophagectomy.
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OBJECTIVE: Evaluate magnetic resonance imaging factors associated with osteoporotic vertebral compression fractures. MATERIALS AND METHODS: We retrospectively reviewed 457 patients' records. Age, sex, and body mass index were recorded. Two blinded readers measured psoas major and paraspinal muscle areas at the L3 vertebral body level on transverse T2-weighted magnetic resonance images and the mean apparent diffusion coefficient values of the non-fractured vertebrae from Th12 to L5. Inter-reader reliability for continuous variables was assessed by intraclass correlation coefficients. RESULTS: We evaluated 210 patients (103 [49.0%] men). The osteoporotic vertebral compression fractures group was older and had lower BMI and smaller psoas major and paraspinal muscle areas than the group without vertebral compression fractures (p < 0.001). The mean apparent diffusion coefficient was weakly correlated with paraspinal muscle area in the osteoporotic vertebral compression fractures group. The intraclass correlation coefficient value was 0.83, and the intraclass correlation coefficients of the psoas major and paraspinal muscles were 0.94 and 0.97, respectively. Multivariate analysis revealed that decreased psoas major and paraspinal muscle areas and increased mean apparent diffusion coefficient values were significantly associated with the presence of osteoporotic vertebral compression fractures (all p < 0.05). Psoas major and paraspinal muscle areas showed relatively high predictive accuracy (57%, 61%). CONCLUSION: Psoas major and paraspinal muscle areas at the L3 level and the mean apparent diffusion coefficient value of non-fractured vertebrae from the Th12 to L5 level were associated with osteoporotic vertebral compression fractures. This may contribute to detecting the potential risk of healthy individuals developing osteoporotic vertebral compression fractures.
Subject(s)
Fractures, Compression , Osteoporotic Fractures , Spinal Fractures , Male , Humans , Female , Fractures, Compression/diagnostic imaging , Paraspinal Muscles/pathology , Spinal Fractures/diagnostic imaging , Retrospective Studies , Reproducibility of Results , Magnetic Resonance Imaging , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/pathology , Lumbar Vertebrae/pathologyABSTRACT
Purpose: This retrospective cohort study assessed the efficiency of non-enhanced magnetic resonance imaging (MRI) for differentiating gallbladder cancer (GBC) from gallbladder polyps (GBPs) measuring ≥ 10 mm. Material and methods: Patients diagnosed with GBCs or GBPs ≥ 10 mm and GBC ≤ T2 stage were eligible for inclusion. Two independent blinded readers assessed the continuity of the mucosal and muscular layers (CMML; present or absent) and normalised signal intensity ratio (NIR) on the apparent diffusion coefficient map (NIR-ADC), T1-weighted image (NIR-T1WI), and T2-weighted half-Fourier acquisition single-shot turbo spin-echo image. Univariate and multivariate logistic regression analyses and interobserver agreement analyses were performed to detect predictive variables differentiating GBCs from GBPs. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance. A reproducibility test was performed to verify the predictive variables. Results: Multivariate analysis showed significant differences in CMML, NIR-ADC, and NIR-T1WI (p < 0.001). The positive predictive value (PPV) and specificity of the absence of CMML were approximately 100%. The CMML showed the best specificity, accuracy, and PPV in the reproducibility study. The sensitivity of CMML alone was approximately 50%, whereas it increased to approximately 70% when combined with NIR-ADC. The diagnostic performance of the combination, including sensitivity, was almost like that of tumour size. The combined tumour size and CMML assessment showed higher diagnostic performance than tumour size alone. Conclusions: The absence of CMML and NIR-ADC ≤ 1.86 helped in differentiating GBCs from GBPs. Evaluation of the absence of CMML and measurement of tumour size could better aid in determining between the two than measurement of tumour size alone.
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OBJECTIVES: This study evaluated the association between aortic valve calcification (AVC) and aortic stenosis (AS) by scoring the AVC to determine the threshold scores for significant AS on non-electrocardiographic (ECG)-gated computed tomography (CT). METHODS: We retrospectively analyzed the AVC scores of 5385 patients on non-contrast non-ECG-gated CT, who underwent transthoracic echocardiography (TTE) from March 1, 2013, to December 26, 2019, at our institution. Multivariable logistic regression models were used to identify potential risk factors for significant AS. The thresholds for significant AS were computed using receiver operator characteristic (ROC) curves, based on the AVC scores after propensity score matching. RESULTS: A significant association was found between AS and age (p < 0.001; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), female sex (p < 0.001; OR, 4.5; 95% CI, 2.75-7.36), bicuspid aortic valve (p < 0.001; OR, 23.2; 95% CI, 7.35-72.9), and AVC score (AVC score/100) (p < 0.001; OR, 1.82; 95% CI, 1.71-1.95). All sex-specific AVC thresholds for significant AS (moderate and over AS severity, moderate and over AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.939-0.968; sensitivity, 84.6-96%; specificity, 84.2-97.1%). CONCLUSIONS: We determined the optimal AVC threshold scores for significant AS, which may aid in diagnosing significant asymptomatic AS on incidental detection of AVC through non-ECG-gated CT for non-cardiac indications. KEY POINTS: ⢠Increased frequency of non-electrocardiographic (ECG)-gated computed tomography (CT) for non-cardiac indications has led to the increased incidental identification of aortic valve calcification (AVC). ⢠It is important to identify patients with significant aortic stenosis (AS) who require additional echocardiographic assessment on incidental detection of AVC via non-ECG-gated CT. ⢠We determined the AVC thresholds with high sensitivity and specificity to identify significant AS on non-ECG-gated CT, which could lead to early diagnosis of asymptomatic significant AS and improved prognosis.
Subject(s)
Aortic Valve Stenosis , Aortic Valve , Male , Humans , Female , Aortic Valve/diagnostic imaging , Retrospective Studies , Multidetector Computed Tomography/methods , Aortic Valve Stenosis/diagnostic imaging , Severity of Illness IndexABSTRACT
OBJECTIVE: The purpose of this study was to evaluate the utility of submucosal linear enhancement on dynamic computed tomography (CT) for patients with internal hemorrhoids. METHODS: We retrospectively reviewed patients who were admitted to our institution due to acute lower gastrointestinal bleeding and underwent both dynamic CT and colonoscopy. The presence of submucosal linear enhancement of the intestinal wall from the lower rectum to the anal canal was evaluated using arterial-phase CT images. Based on these images, patients were then classified into 2 groups by 2 blinded radiologists, as follows: group A (absence of submucosal linear enhancement) and group B (presence of submucosal linear enhancement). The relationship between the groups and the risk of bleeding in internal hemorrhoids was evaluated using the size and range of internal hemorrhoids measured during colonoscopy as reference standards. RESULTS: A total of 94 patients were reviewed; of these, 62 patients without submucosal linear enhancement were classified into group A, and 32 patients with submucosal linear enhancement were classified into group B. Group B showed a significantly greater range ( P = 0.017) and size ( P = 0.002) of internal hemorrhoids. The Cohen κ coefficient value for the group classifications between the 2 radiologists was 0.66. CONCLUSIONS: Submucosal linear enhancement on arterial-phase CT images could be a predictive finding suggesting the presence of internal hemorrhoids with a high risk of bleeding.
Subject(s)
Hemorrhoids , Gastrointestinal Hemorrhage/diagnostic imaging , Hemorrhoids/diagnostic imaging , Humans , Rectum , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
PURPOSE: To assess the value of histogram analysis for differentiating a high-risk thymic epithelial tumor (TET) from a low-risk TET using T2-weighted images and the apparent diffusion coefficient (ADC). METHODS: Forty-nine patients with histopathologically proven TET after thymectomy were enrolled in this study and retrospectively classified as having low-risk TET (low-risk thymoma) or high-risk TET (high-risk thymoma or thymic carcinoma). Twelve parameters were obtained from the quantitative histogram analysis. The histogram parameters were compared using the Mann-Whitney U test. Diagnostic efficacy was estimated by receiver-operating characteristic curve analysis. RESULTS: Twenty-five patients were classified as having low-risk TET and 24 as having high-risk TET. The mean ADC value showed diagnostic efficacy for differentiating high-risk TET from low-risk TET, with an area under the curve of 0.7, and was better than when using conventional methods alone. CONCLUSION: The ADC-based histogram analysis could help to differentiate between high-risk and low-risk TETs.
Subject(s)
Magnetic Resonance Imaging/methods , Neoplasms, Glandular and Epithelial/diagnostic imaging , Thymus Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging/methods , Evaluation Studies as Topic , Female , Humans , Male , Middle Aged , Neoplasms, Glandular and Epithelial/surgery , Predictive Value of Tests , Retrospective Studies , Thymus Gland/diagnostic imaging , Thymus Gland/surgery , Thymus Neoplasms/surgeryABSTRACT
PURPOSE: To investigate the predictors of intraductal papillary mucinous neoplasms of the pancreas (IPMNs) with high-grade dysplasia, using 2-dimensional (2D) analysis and 3-dimensional (3D) volume-of-interest-based apparent diffusion coefficient (ADC) histogram analysis. MATERIAL AND METHODS: The data of 45 patients with histopathologically confirmed IPMNs with high-grade or low-grade dysplasia were retrospectively assessed. The 2D analysis included lesion-to-spinal cord signal intensity ratio (LSR), minimum ADC value (ADCmin), and mean ADC value (ADCmean). The 3D analysis included the overall mean (ADCoverall mean), mean of the bottom 10th percentile (ADCmean0-10), mean of the bottom 10-25th percentile (ADCmean10-25), mean of the bottom 25-50th percentile (ADCmean25-50), skewness (ADCskewness), kurtosis (ADCkurtosis), and entropy (ADCentropy). Diagnostic performance was compared by analysing the area under the receiver operating characteristic curve (AUC). Inter-rater reliability was assessed by blinded evaluation using the intraclass correlation coefficient. RESULTS: There were 16 and 29 IPMNs with high- and low-grade dysplasia, respectively. The LSR, ADCoverall mean, ADCmean0-10, ADCmean10-25, ADCmean25-50, and ADCentropy showed significant between-group differences (AUC = 72-93%; p < 0.05). Inter-rater reliability assessment showed almost perfect agreement for LSR and substantial agreement for ADCoverall mean and ADCentropy. Multivariate logistic regression showed that ADCoverall mean and ADCentropy were significant independent predictors of malignancy (p < 0.05), with diagnostic accuracies of 80% and 73%, respectively. CONCLUSION: ADCoverall mean and ADCentropy from 3D analysis may assist in predicting IPMNs with high-grade dysplasia.
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Accurate diagnosis and therapeutic intervention at an early stage is paramount for the management of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), which are the two major types of inflammatory arthritis that involve the hand joints. As more disease-specific medications are developed, medication selection according to the correct diagnosis becomes more important. A delay in diagnosis and inappropriate medication selection may result in poor functional prognosis. However, clinical differentiation between RA and PsA can be challenging and may become largely dependent on imaging interpretation results. Although there is substantial overlap in the imaging findings of RA and PsA, there are differences in the affected primary target sites, reflected by the various patterns of joint involvement, and different microanatomic localization of abnormalities within a single joint in each disease. Therefore, appropriate use of various imaging modalities and accurate image interpretation add significant value to the diagnosis and treatment process. The synovio-entheseal complex is an important concept for understanding the imaging features of PsA. The authors review the different features of RA and PsA of the hands seen with various imaging modalities, including radiography, US, MRI, and dual-energy CT, with updates on the contemporary role of imaging in diagnosis and treatment. The radiologist should have sufficient knowledge to interpret imaging findings and understand the strengths and weaknesses of each modality to recommend the appropriate imaging method and differentiate both diseases accurately. ©RSNA, 2020.
Subject(s)
Arthritis, Psoriatic/diagnostic imaging , Arthritis, Rheumatoid/diagnostic imaging , Hand/diagnostic imaging , Multimodal Imaging , Diagnosis, Differential , HumansABSTRACT
Transfer RNAs (tRNAs) perform essential tasks for all living cells. They are major components of the ribosomal machinery for protein synthesis and they also serve in non-ribosomal pathways for regulation and signaling metabolism. We describe the development of a genetically encoded fluorescent tRNA fusion with the potential for imaging in live Escherichia coli cells. This tRNA fusion carries a Spinach aptamer that becomes fluorescent upon binding of a cell-permeable and non-toxic fluorophore. We show that, despite having a structural framework significantly larger than any natural tRNA species, this fusion is a viable probe for monitoring tRNA stability in a cellular quality control mechanism that degrades structurally damaged tRNA. Importantly, this fusion is active in E. coli live-cell protein synthesis allowing peptidyl transfer at a rate sufficient to support cell growth, indicating that it is accommodated by translating ribosomes. Imaging analysis shows that this fusion and ribosomes are both excluded from the nucleoid, indicating that the fusion and ribosomes are in the cytosol together possibly engaged in protein synthesis. This fusion methodology has the potential for developing new tools for live-cell imaging of tRNA with the unique advantage of both stoichiometric labeling and broader application to all cells amenable to genetic engineering.
Subject(s)
Aptamers, Nucleotide/chemistry , Protein Biosynthesis , RNA Probes/chemistry , RNA, Transfer/chemistry , RNA, Transfer/metabolism , Aptamers, Nucleotide/metabolism , Benzyl Compounds/chemistry , Escherichia coli/genetics , Fluorescent Dyes , Imidazolines/chemistry , Microscopy, Fluorescence , Ribosomes/metabolism , Spinacia oleracea/geneticsABSTRACT
PURPOSE: To determine the differentiating features between non-hypervascular pancreatic neuroendocrine tumour (PNET) and pancreatic ductal adenocarcinoma (PDAC) on dynamic computed tomography (CT) and non-enhanced magnetic resonance imaging (MRI). MATERIAL AND METHODS: We enrolled 102 patients with non-hypervascular PNET (n = 15) or PDAC (n = 87), who had undergone dynamic CT and non-enhanced MRI. One radiologist evaluated all images, and the results were subjected to univariate and multivariate analyses. To investigate reproducibility, a second radiologist re-evaluated features that were significantly different between PNET and PDAC on multivariate analysis. RESULTS: Tumour margin (well-defined or ill-defined) and enhancement ratio of tumour (ERT) showed significant differences in univariate and multivariate analyses. Multivariate analysis revealed a predominance of well-defined tumour margins in non-hypervascular PNET, with an odds ratio of 168.86 (95% confidence interval [CI]: 10.62-2685.29; p < 0.001). Furthermore, ERT was significantly lower in non-hypervascular PNET than in PDAC, with an odds ratio of 85.80 (95% CI: 2.57-2860.95; p = 0.01). Sensitivity, specificity, and accuracy were 86.7%, 96.6%, and 95.1%, respectively, when the tumour margin was used as the criteria. The values for ERT were 66.7%, 98.9%, and 94.1%, respectively. In reproducibility tests, both tumour margin and ERT showed substantial agreement (margin of tumour, κ = 0.6356; ERT, intraclass correlation coefficients (ICC) = 0.6155). CONCLUSIONS: Non-hypervascular PNET showed well-defined margins and lower ERT compared to PDAC, with significant differences. Our results showed that non-hypervascular PNET can be differentiated from PDAC via dynamic CT and non-enhanced MRI.
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PURPOSE: To evaluate the diagnostic performance of combining non-enhanced magnetic resonance imaging (MRI) and non-enhanced endoscopic ultrasonography (EUS) for assessing the malignant potential of lesions in patients with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). MATERIAL AND METHODS: Data from 38 patients histopathologically diagnosed with IPMN adenomas or IPMN adenocarcinomas were retrospectively analysed. Preliminary univariate and multivariate analyses were conducted to identify statistically significant associations. Three blinded radiologists evaluated the image sets to assess the diagnostic performance of combined use of non-enhanced MRI and EUS as opposed to non-enhanced MRI alone in distinguishing malignant from benign lesions. Observer performance and interobserver variability were determined using receiver-operating-characteristic curve analysis and weighted κ statistics. RESULTS: Multivariate analyses identified a significant difference between the abrupt change in the main pancreatic duct (MPD) calibre with distal pancreatic atrophy and the signal intensity of lesion-to-spinal cord ratio on MRI; a significant difference was observed in MPD size on EUS. Diagnostic performance assessments of the image sets did not differ significantly between the blinded radiologists. CONCLUSIONS: The clinical utility of non-enhanced EUS may be attributive in evaluating IPMN that has already been evaluated by non-enhanced MRI.
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PURPOSE: Thyroglobulin assay is important to assess the residual or recurrence of differentiated thyroid cancer (DTC). Patients with positive serum thyroglobulin levels after radioactive iodine (RAI) adjuvant therapy could achieve long-term recurrence-free survival (RFS). The patient's prognosis could not be confidently estimated based solely on the evaluation of thyroglobulin levels. We investigated the recurrence rate and RFS of patients who received adjuvant RAI therapy after surgery for DTC to clarify the relationship between changes in pre- and post-therapy serum thyroglobulin levels and RFS. MATERIALS AND METHODS: Patients who underwent adjuvant RAI therapy between May 2007 and March 2021 were included in this study, whereas those with positive anti-thyroglobulin antibodies, distant metastases, or gross residual tumors were excluded. The change in pre- and post-treatment serum thyroglobulin levels under thyroid-stimulating hormone stimulation was calculated and classified as follows: group A, thyroglobulin levels decreased by Ë10%; group B, thyroglobulin levels within a range of 10% or less; and group C, thyroglobulin levels increased by Ë10%. RFS outcomes were analyzed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, and multivariate analysis was performed using the Cox proportional hazard model. RESULTS: A total of 74 patients were included. Relapse was seen in 13 of 46 patients in group A, 9 of 15 in group B, and 10 of 13 in group C. Median RFS was 129.00 (95% confidence interval CI 77.79-180.21), 113.00 (95% CI 86.83-139.17), and 33 months (95% CI 6.026-59.974) in groups A, B, and C, respectively. Patients in group C exhibited significantly shorter RFS than those in groups A and B (P = 0.001). CONCLUSIONS: Changes in thyroglobulin levels pre- and post-therapy were associated with RFS. Patients with decreased post-therapy thyroglobulin levels had a favorable prognosis, even if their thyroglobulin levels were positive after RAI therapy.
Subject(s)
Adenocarcinoma , Thyroid Neoplasms , Humans , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Thyroglobulin , Iodine Radioisotopes/therapeutic use , Retrospective Studies , Case-Control Studies , Thyroidectomy , Neoplasm Recurrence, Local , Adenocarcinoma/surgeryABSTRACT
BACKGROUND: We previously conducted a retrospective study investigating pancreatic morphological abnormalities that lead to early diagnosis of pancreatic cancer (PC) using computed tomography (CT). We reviewed 41 of 308 PC patients between 2011 and 2017 who had previously undergone CT to look for morphological changes leading to cancer development. In 24 patients (58.5%), a K-shaped constriction of the pancreas ("K-sign") was observed before the appearance of cancer. This study aimed to investigate whether an early PC diagnosis is possible by prospective CT follow-up of patients with the K-sign. METHODS: We investigated PC development through prospective surveillance of patients exhibiting K-signs identified on CT. RESULTS: Of approximately 87 000 CT scans performed between April 2019 and August 2022, the K-sign was observed in 54 patients. A total of 30 patients provided informed consent and were subsequently monitored using CT. Five patients (16.7%) were diagnosed with PC and underwent surgery after 3-24 months follow-up. Pathologically, four of five patients (80%) were diagnosed with early-stage pancreatic cancer (stage 0-IA). All patients exhibited defects in acinar structure, fibrous tissue, fat replacement, and inflammatory cells, suggesting their potential involvement in PC development. CONCLUSION: The detection and surveillance of the K-sign may be helpful for early PC diagnosis.
Subject(s)
Early Detection of Cancer , Pancreatic Neoplasms , Humans , Prospective Studies , Retrospective Studies , Pancreas , Pancreatic Neoplasms/surgery , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND: Omental artery aneurysm (OAA) is an extremely rare visceral artery aneurysm. Ruptured OAAs are associated with a high mortality rate. Transcatheter arterial embolization (TAE) has been used to treat OAA in recent years. However, the risk of omental ischemia due to TAE remains unclear. Therefore, this study aimed to investigate the efficacy and safety of TAE of OAA as a first-line treatment. METHODS: Fifteen patients with true aneurysms or pseudoaneurysms who underwent OAA-TAE between 1 April 2010 and 31 December 2022 were included in this study. The technical and clinical outcomes, the incidence of omental infarction after TAE as a major complication, OAA-TAE techniques, radiological findings on computed tomography angiography and angiogram, and patient characteristics were evaluated. RESULTS: Fifteen patients (nine men, six women; age, 69.8 ± 18.59 years) underwent TAE of OAAs (mean aneurysm size of 9.30 ± 6.10 mm) located in the right gastroepiploic (n = 9), left gastroepiploic (n = 1), and epiploic (n = 5) arteries. All patients with ruptured (n = 6) and unruptured (n = 9) OAA successfully underwent TAEs using coils, n-butyl-2-cyanoacrylate, or gelatin sponges. Hepatic artery thrombosis and coil migration were observed during the procedure; however, these adverse events were manageable. Transfusion of red blood cell units (4.66 ± 1.63 units) was required only in cases with ruptured OAAs after TAE. Additional surgery or TAE due to rupture or rerupture of OAA and omental infarction was not required during the postoperative and follow-up periods. CONCLUSION: The OAA-TAE can effectively treat ruptured and unruptured OAAs, and the risk of omental infarction after OAA-TAE may not be high.
Subject(s)
Aneurysm , Embolization, Therapeutic , Male , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Treatment Outcome , Arteries , Embolization, Therapeutic/adverse effects , Retrospective Studies , Infarction/etiologyABSTRACT
Charcot-Marie-Tooth (CMT) disease comprises a genetically and clinically heterogeneous group of peripheral nerve disorders characterized by impaired distal motor and sensory function. Mutations in three genes encoding aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT disease primarily associated with an axonal pathology. ARSs are ubiquitously expressed, essential enzymes responsible for charging tRNA molecules with their cognate amino acids. To further explore the role of ARSs in CMT disease, we performed a large-scale mutation screen of the 37 human ARS genes in a cohort of 355 patients with a phenotype consistent with CMT. Here we describe three variants (p.Leu133His, p.Tyr173SerfsX7, and p.Ile302Met) in the lysyl-tRNA synthetase (KARS) gene in two patients from this cohort. Functional analyses revealed that two of these mutations (p.Leu133His and p.Tyr173SerfsX7) severely affect enzyme activity. Interestingly, both functional variants were found in a single patient with CMT disease and additional neurological and non-neurological sequelae. Based on these data, KARS becomes the fourth ARS gene associated with CMT disease, indicating that this family of enzymes is specifically critical for axon function.
Subject(s)
Charcot-Marie-Tooth Disease/genetics , Heterozygote , Lysine-tRNA Ligase/genetics , Models, Molecular , Peripheral Nervous System Diseases/genetics , Protein Conformation , Amino Acid Sequence , Base Sequence , Cohort Studies , DNA Mutational Analysis , Humans , Molecular Sequence Data , Mutation, Missense/geneticsABSTRACT
The cell cycle is a temporal program that regulates DNA synthesis and cell division. When we compared the codon usage of cell cycle-regulated genes with that of other genes, we discovered that there is a significant preference for non-optimal codons. Moreover, genes encoding proteins that cycle at the protein level exhibit non-optimal codon preferences. Remarkably, cell cycle-regulated genes expressed in different phases display different codon preferences. Here, we show empirically that transfer RNA (tRNA) expression is indeed highest in the G2 phase of the cell cycle, consistent with the non-optimal codon usage of genes expressed at this time, and lowest toward the end of G1, reflecting the optimal codon usage of G1 genes. Accordingly, protein levels of human glycyl-, threonyl-, and glutamyl-prolyl tRNA synthetases were found to oscillate, peaking in G2/M phase. In light of our findings, we propose that non-optimal (wobbly) matching codons influence protein synthesis during the cell cycle. We describe a new mathematical model that shows how codon usage can give rise to cell-cycle regulation. In summary, our data indicate that cells exploit wobbling to generate cell cycle-dependent dynamics of proteins.
Subject(s)
Biological Clocks/genetics , Cell Cycle/genetics , Codon/genetics , Genes/physiology , Proteins/metabolism , Arabidopsis , Base Sequence , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/physiology , Gene Expression Regulation/genetics , Genetic Code/physiology , Humans , Models, Biological , Models, Theoretical , Proteins/genetics , Saccharomyces cerevisiae , SchizosaccharomycesABSTRACT
PURPOSE: The purpose of this study was to investigate the incidence of multiple organ calcification and the correlation between multiple organ calcification and clinical severity in patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome. METHODS: We retrospectively identified 13 patients with TAFRO syndrome who were treated at our hospital between February 2019 and March 2021. Computed tomography (CT) images of TAFRO patients, which were acquired at admission and one month after admission, were evaluated. Additionally, clinical and laboratory data related to organ calcification and severity classification of TAFRO syndrome were investigated. The correlation between the presence of organ calcification on CT and TAFRO syndrome-severity classification was evaluated. RESULTS: One month after admission, calcification of the myocardium, adrenal glands, gallbladder wall, pancreas, kidney, skeletal muscle, and skin were observed in 38%, 46%, 15%, 15%, 15%, 23%, and 15% of the thirteen patients, respectively. The occurrence rate of calcifications in the myocardium, adrenal glands, and skeletal muscle was significantly higher in patients with a grade 4 or higher clinical severity than in those with a level up to grade 3 (p = 0.001, p = 0.005, and p = 0.035, respectively). CONCLUSIONS: Our results suggest that the higher the clinical severity in patients with TAFRO syndrome, the higher is the frequency of calcification in the myocardium, adrenal glands, and skeletal muscle; therefore, the assessment of these organ calcifications on CT images may be useful in predicting the severity of TAFRO syndrome.