The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components

In the anterior foregut (AFG) of mouse embryos, the transcription factor SOX2 is expressed in the epithelia of the esophagus and proximal branches of respiratory organs comprising the trachea and bronchi, whereas NKX2.1 is expressed only in the epithelia of respiratory organs. Previous studies using hypomorphic Sox2 alleles have indicated that reduced SOX2 expression causes the esophageal epithelium to display some respiratory organ characteristics. In the present study, we produced mouse embryos with AFG-specific SOX2 deficiency. In the absence of SOX2 expression, a single NKX2.1-expressing epithelial tube connected the pharynx and the stomach, and a pair of bronchi developed in the middle of the tube. Expression patterns of NKX2.1 and SOX9 revealed that the anterior and posterior halves of SOX2-deficient AFG epithelial tubes assumed the characteristics of the trachea and bronchus, respectively. In addition, we found that mesenchymal tissues surrounding the SOX2-deficient NKX2.1-expressing epithelial tube changed to those surrounding the trachea and bronchi in the anterior and posterior halves, as indicated by the arrangement of smooth muscle cells and SOX9-expressing cells and by the expression of Wnt4 (esophagus specific), Tbx4 (respiratory organ specific), and Hoxb6 (distal bronchus specific). The impact of mesenchyme-derived signaling on the early stage of AFG epithelial specification has been indicated. Our study demonstrated an opposite trend where epithelial tissue specification causes concordant changes in mesenchymal tissues, indicating a reciprocity of epithelial-mesenchymal interactions

Segmental mobility with spondylolisthesis

Purpose : To evaluate segmental mobility with degenerative lumbar spondylolisthesis (DLS), upright lateral flexion-extension radiographs (FE) are widely used. However, some authors have described that a combination of lateral radiographs in the standing position and supine sagittal image (SS) reveal more segmental mobility than FE. The purpose of this study was to investigate the optimal method for evaluating segmental mobility with DLS. Methods : We included 92 consecutive Japanese patients diagnosed with DLS. Sagittal translation (ST) determined by FE and SS were compared. Pathological instability was defined as ST more than 8% of the upper vertebra. Patients were divided into those diagnosed with pathological instability in FE (PI-FE) and those diagnosed with SS (PI-SS), and lumbar lordosis (LL) in the standing position in each group were compared. Results : ST in FE was significantly greater than in SS. Of 92 patients, 31 had pathological instability in FE or SS ; 17 patients had PI-FE, and 10 patients had PI-SS. LL in the standing position in PI-FE was significantly smaller than in PI-SS. Conclusions : ST in FE was greater than that in SS, contrary to previous studies’ reports on Caucasians. Since Japanese individuals have smaller LL than Caucasians, FE tends to reveal more segmental mobility than SS

Automated classification of pulmonary nodules through a retrospective analysis of conventional CT and two-phase PET images in patients undergoing biopsy

Objective(s): Positron emission tomography/computed tomography (PET/CT) examination is commonly used for the evaluation of pulmonary nodules since it provides both anatomical and functional information. However, given the dependence of this evaluation on physician’s subjective judgment, the results could be variable. The purpose of this study was to develop an automated scheme for the classification of pulmonary nodules using early and delayed phase PET/ CT and conventional CT images.Methods: We analysed 36 early and delayed phase PET/CT images in patients who underwent both PET/CT scan and lung biopsy, following bronchoscopy. In addition, conventional CT images at maximal inspiration were analysed. The images consisted of 18 malignant and 18 benign nodules. For the classification scheme, 25 types of shape and functional features were first calculated from the images. The random forest algorithm, which is a machine learning technique, was used for classification.Results: The evaluation of the characteristic features and classification accuracy was accomplished using collected images. There was a significant difference between the characteristic features of benign and malignant nodules with regard to standardised uptake value and texture. In terms of classification performance, 94.4% of the malignant nodules were identified correctly assuming that 72.2% of the benign nodules were diagnosed accurately. The accuracy rate of benign nodule detection by means of CT plus two-phase PET images was 44.4% and 11.1% higher than those obtained by CT images alone and CT plus early phase PET images, respectively.Conclusion: Based on the findings, the proposed method may be useful to improve the accuracy of malignancy analysis

Phosphorylated Platelet-Derived Growth Factor Receptor-Positive Cells With Anti-apoptotic Properties Accumulate in the Synovium of Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease caused by inflammation of the synovium and characterized by chronic polyarthritis that destroys bone and cartilage. Fibroblast-like synoviocytes (FLSs) in the synovium of patients with RA can promote cartilage and bone destruction by producing proteins such as matrix metalloproteinases and receptor activator of NF-κB ligand, thereby representing an important therapeutic target for RA. FLSs have several phenotypes depending on which cell surface proteins and adhesion factors are expressed. Identifying the cellular functions associated with different phenotypes and methods of controlling them are considered essential for developing therapeutic strategies for RA. In this study, synovial tissue was collected from patients with RA and control subjects who required surgery due to ligament injury or fracture. Immunohistological analysis was used to investigate the rates of positivity for phosphorylated platelet-derived growth factor receptor-αβ (pPDGFRαβ) and cadherin-11 (CDH11) expression, and apoptosis-related markers were assessed for each cell phenotype. Next, FLSs were isolated in vitro and stimulated with tumor necrosis factor-α (TNF-α) in addition to a combination of PDGF and transforming growth factor (2GF) to investigate pPDGFRαβ and CDH11 expression and the effects of the inhibition of TNF and cyclin-dependent kinase (CDK) 4/6 on FLSs. Immunohistological analysis showed a large percentage of pPDGFRαβ+CDH11– cells in the sub-lining layer (SL) of patients with RA. These cells exhibited increased B-cell lymphoma-2 expression, reduced TNF receptor-1 expression, resistance to cell death, and abnormal proliferation, suggesting a tendency to accumulate in the synovium. Further, in vitro 2GF stimulation of FLSs lowered, whereas 2GF + TNF stimulation increased the pPDGFRαβ/CDH11 ratio. Hypothesizing that FLSs stimulated with 2GF + TNF would accumulate in vivo in RA, we determined the therapeutic effects of TNF and CDK4/6 inhibitors. The TNF inhibitor lowered the pPDGFRαβ/CDH11 ratio, whereas the CDK4/6 inhibitor suppressed cell proliferation. However, a synergistic effect was not observed by combining both the drugs. We observed an increase in pPDGFRαβ+CDH11– cells in the SL of the RA synovium and accumulation of these cells in the synovium. We found that the TNF inhibitor suppressed FLS activity and the CDK4/6 inhibitor reduced cell proliferation

A case of strangulated ileus caused by internal hernia through a defect in the broad ligament of the uterus

A 41-year-old woman was admitted to our hospital because of lower abdominal pain. She had no history of laparotomy. An abdominal CT scan at the time of admission indicated closed-loop intestinal obstruction of the small intestine within the pelvis and deviation of the uterus to the right. We diagnosed this as a strangulated internal hernia and decided to conduct an emergency operation. The ileum had herniated through a defect in the broad ligament of the uterus. The strangulated intestinal loop, which was about 25cm long, was released, and the defect of the broad ligament was closed. The postoperative course was uneventful. The differential diagnosis of intestinal obstruction should include internal hernia, especially in the absence of a previous laparotomy. An abdominal CT scan is quite useful for the preoperative and prompt diagnosis of internal hernia through a defect in the broad ligament of the uterus

Effects of Initial Graft Tension during Anterior Talofibular Ligament Reconstruction on Ankle Kinematics, Laxity, and In-situ Forces of the Reconstructed Graft

前距腓靭帯は，足関節の安定性に関わる重要な靱帯である．前距腓靱帯の損傷後に慢性的な足関節の不安定性が残存した場合，前距腓靱帯再建手術が必要となるが，その際に再建靭帯にかける適切な張力について研究した報告はなかった．本論文では，再建靭帯にかける張力の違いが，足関節のキネマティクス，制動性，術後の靱帯張力に及ぼす影響と適切な再建靭帯初期固定張力を明らかにした

Assessment of Coronary atherosclerosis in patients with familial hypercholesterolemia by coronary computed tomography angiography

The aims of this study were (1) to determine whether the accumulation of coronary plaque burden assessed with coronary computed tomography angiography (CCTA) can predict future events and (2) to estimate the onset and progression of coronary atherosclerosis in patients with familial hypercholesterolemia (FH). Consecutive 101 Japanese patients with heterozygous FH (men= 52, mean age 56 ± 16years, mean low-density lipoprotein cholesterol 264 ± 58mg/dl) who underwent 64-detector row CCTA without known coronary artery disease were retrospectively evaluated by assigning a score (0 to 5) to each of 17 coronary artery segments according to the Society of Cardiovascular Computed Tomography guidelines. Those scores were summed and subsequently natural log transformed. The periods to major adverse cardiac events (MACE) were estimated using multivariable Cox proportional hazards models. During the follow-up period (median 941days), 21 MACE had occurred. Receiver operating characteristic curve analyses identified a plaque burden score of 3.35 (raw score 28.5) as the optimal cutoff for predicting a worse prognosis. Multivariate Coxregression analysis identified the presence of a plaque score ≥3.35 as a significant independent predictor of MACE (hazard ratio= 3.65; 95% confidence interval 1.32 to 25.84, p<0.05). The regression equations were Y= 0.68. X- 15.6 (r= 0.54, p <0.05) in male and Y= 0.74. X- 24.8 (r= 0.69, p <0.05) in female patients with heterozygous FH. In conclusion, coronary plaque burden identified in a noninvasive, quantitative manner was significantly associated with future coronary events in Japanese patients with heterozygous FH and that coronary atherosclerosis may start to develop, on average, at age 23 and 34years in male and female patients with heterozygous FH, respectively

High-intensity interval training using electrical stimulation ameliorates muscle fatigue in chronic kidney disease-related cachexia by restoring mitochondrial respiratory dysfunction

BackgroundExercise, especially high-intensity interval training (HIIT), can increase mitochondrial respiratory capacity and enhance muscular endurance, but its systemic burden makes it difficult to safely and continuously prescribe for patients with chronic kidney disease (CKD)-related cachexia who are in poor general condition. In this study, we examined whether HIIT using electrical stimulation (ES), which does not require whole-body exercise, improves muscle endurance in the skeletal muscle of 5/6 nephrectomized rats, a widely used animal model for CKD-related cachexia.MethodsMale Wistar rats (10 weeks old) were randomly assigned to a group of sham-operated (Sham) rats and a group of 5/6 nephrectomy (Nx) rats. HIIT was performed on plantar flexor muscles in vivo with supramaximal ES every other day for 4 weeks to assess muscle endurance, myosin heavy-chain isoforms, and mitochondrial respiratory function in Nx rats. A single session was also performed to identify upstream signaling pathways altered by HIIT using ES.ResultsIn the non-trained plantar flexor muscles from Nx rats, the muscle endurance was significantly lower than that in plantar flexor muscles from Sham rats. The proportion of myosin heavy chain IIa/x, mitochondrial content, mitochondrial respiratory capacity, and formation of mitochondrial respiratory supercomplexes in the plantaris muscle were also significantly decreased in the non-trained plantar flexor muscles from Nx rats than compared to those in plantar flexor muscles from Sham rats. Treatment with HIIT using ES for Nx rats significantly improved these molecular and functional changes to the same degrees as those in Sham rats. Furthermore, a single session of HIIT with ES significantly increased the phosphorylation levels of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK), pathways that are essential for mitochondrial activation signaling by exercise, in the plantar muscles of both Nx and Sham rats.ConclusionThe findings suggest that HIIT using ES ameliorates muscle fatigue in Nx rats via restoration of mitochondrial respiratory dysfunction with activation of AMPK and p38 MAPK signaling. Our ES-based HIIT protocol can be performed without placing a burden on the whole body and be a promising intervention that is implemented even in conditions of reduced general performance status such as CKD-related cachexia