• Clinical and Experimental Reproductive Medicine
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• v.26 no.1
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• pp.103-109
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• 1999

Objective: Heat shock protein 70-2 (Hsp70-2) gene knockout mice are found to have premeiotic arrest at the primary spermatocyte stage with a complete absence of spermatids and spermatozoa. This observation led to the hypothesis that hspA2 may be disrupted in human testes with abnormal spermatogenesis. To test this hypothesis, we studied the mRNA expression of hspA2 in infertile men with azoospermia. Design: The mRNA expression were analyzed by competitive RT-PCR among testes with normal spermatogenesis, pachytene spermatocyte arrest, and sertoli-cell only syndrome. Materials and methods: Testicular biopsy was performed in men with azoospermia (n=15). Specimens were subdivided into three groups: (group 1) normal spermatogenesis (n=5), (group 2) spermatocyte arrest (n=5), (group 3) Sertoli-cell only syndrome (n=5). Total RNA was extracted by Trizol reagent. Total extracted RNA was reverse transcribed into cDNA and amplified by PCR using specific primers for hspA2 target cDNAs. A competitive cDNA fragment was constructed by deleting a defined fragment from the target cDNA sequence, and then coamplified with the target cDNA for competitive PCR. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as an internal control. Results: On Competitive RT-PCR analyses for hspA2 mRNA, significant amount of hspA2 expression was observed in group 1, whereas a constitutively low level of hspA2 was expressed in groups 2 and 3. Conclusion(s): The study demonstrates that the hspA2 gene expression is down-regulated in human testes with abnormal spermatogenesis, which in turn suggests that hspA2 gene may play a specific role during meiosis in human testes.

• Journal of Genetic Medicine
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• v.16 no.2
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• pp.67-70
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• 2019

Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies that has extremely heterogeneous clinical features and genetic background. The caveolin-3 gene (CAV3) is one of the causative genes. LGMD appears as a clinical continuum, from isolated skeletal muscle involvement to long QT syndrome. Here we report two patients without apparent muscle weakness in a family with CAV3 mutation. A 7-month-old Korean boy visited our muscle clinic because of an incidental finding of elevated serum creatine kinase (CK) concentration (680 IU/L, reference range, 20-270 IU/L) without clinical symptoms. The patient was born after an uneventful pregnancy and showed normal developmental milestones. He developed pseudohypertrophy of his calf muscle during the follow-up. We obtained a muscle biopsy at age 14 months, which showed size variations and degenerating/regenerating myofibers with endomysial fibrosis and immunohistochemical evidence of normal dystrophin. Under the impression of LGMD, we performed target panel sequencing and identified a heterozygous in-frame mutation of CAV3, c.307_312delGTGGTG (p.Val103_Val104del). Immunohistochemical staining of muscle indicated complete loss of caveolin-3 compared with normal control muscle, which supported the variant's pathogenicity. We performed segregation analysis and found that the patient's mother had the same variant with elevated serum CK level (972 IU/L). We report on autosomal dominant familial caveolinopathy caused by a pathogenic variant in CAV3, which was asymptomatic until the fourth decade. This case highlights the utility of next generation sequencing in the diagnosis of muscular dystrophies and the additive role of muscle biopsy to confirm the variants.

• Tuberculosis and Respiratory Diseases
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• v.67 no.6
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• pp.545-550
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• 2009

Background: Endobronchial ultrasonogram (EBUS) has increased the diagnostic yield of a bronchoscopic biopsy of peripheral pulmonary lesions (PPL). This study evaluated the diagnostic yield of EBUS-guided transbronchial biopsy (TBB) and the visibility of EBUS PPL. Methods: Between August 2007 and November 2008, 50 patients (32 men and 18 women, median age, 61.1${\pm}$10 yrs; range, 16 to 80 yrs) whose PPL lesions could not be detected with flexible bronchoscopy were enrolled in this study. Among the 50 patients, 40 cases were malignant lesions (adenocarcinoma 25, squamous cell carcinoma 10, small cell carcinoma 5) and 10 cases were benign lesions (tuberculoma 7, fungal ball 1, other inflammation 2). Results: The mean diameter of the target lesion was 35.4${\pm}$4.3 mm. Of the 50 patients examined, the overall diagnostic yield by EBUS-TBLB was 46.0% (23/50). The visualization yield of EBUS was 66.0% (33/50). A definitive diagnosis of PPL localized by EBUS was established using EBUS-TBLB in 69.6% (23/33) of cases. The diagnostic yields from washing cytology and brushing cytology from a bronchus identified by EBUS were 27.0% and 45.4% respectively. The diagnostic yields reached 78.7% when the three tests (washing cytology, brushing cytology and EBUS-TBLB) were combined. The visualization yield of EBUS in lesions <20 mm was significantly lower than that in lesions ${\geq}$20 mm (p=0.04). The presence of a bronchus leading to a lesion (open bronchus sign) on the chest CT scan was associated with a high visualization yield on EBUS (p=0.001). There were no significant complications associated with EBUS-TBLB. Conclusion: EBUS-TBLB is a safe and effective method for diagnosing PPL. The lesion size and open bronchus signs are significant factors for predicting the visualization of EBUS.

• Tuberculosis and Respiratory Diseases
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• v.82 no.4
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• pp.319-327
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• 2019

Background: Radial probe endobronchial ultrasound (R-EBUS), is effective for tissue diagnosis of lung lesions. We evaluated the diagnostic performance of R-EBUS both a guide-sheath and fluoroscopy and identified factors associated with accurate diagnosis. The feasibility of molecular and genetic testing, using specimens obtained by R-EBUS, was also investigated. Methods: The study retrospectively reviewed 211 patients undergoing R-EBUS without a guide-sheath and fluoroscopy, June 2016-May 2017. After excluding 27 patients of which the target lesion was not reached, 184 were finally included. Multivariate logistic regression was used, to identify factors associated with accurate diagnosis. Results: Among 184 patients, R-EBUS-guided biopsy diagnosed malignancy in 109 patients (59%). The remaining 75 patients (41%) with non-malignant results underwent additional work-ups, and 34 were diagnosed with malignancy. Based on final diagnosis, diagnostic accuracy was 80% (136/170), and sensitivity and specificity for malignancy were 76% (109/143) and 100% (27/27), respectively. In multivariate analysis, peripheral location (adjusted odds ratio [aOR], 3.925; 95% confidence interval [CI], 1.203-12.811; p=0.023), and central position of the probe (aOR, 2.435; 95% CI, 1.424-7.013; p=0.035), were associated with accurate diagnosis of malignancy. Molecular and genetic analyses were successful, in all but one case, with inadequate specimens. Conclusion: R-EBUS-guided biopsy without equipment, is effective for tissue diagnosis. Peripheral location and central position of the radial probe, were crucial for accurate diagnosis. Performance of molecular and genetic testing, using samples obtained by R-EBUS, was satisfactory.

• Radiation Oncology Journal
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• v.28 no.1
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• pp.1-8
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• 2010

Purpose: This retrospective study was performed to evaluate the efficacy of radiation therapy (RT) and to investigate the prognostic factors for thymoma when treated with RT. Materials and Methods: We analyzed 21 patients with thymoma and also received RT from March 2002 to January 2008. The median follow-up time was 37 months (range, 3 to 89 months). The median patient age was 57 years (range, 24 to 77 years) and the gender ratio of males to females was 4：3. Of the 21 patients, complete resections (trans-sternal thymectomy) and R2 resections were performed in 14 and 1 patient, respectively. A biopsy was performed in 6 patients (28.7%). The WHO cell types in the 21 patients were as follows: 1 patient (4.8%) had type A, 10 patients (47.6%) had type B1-3, and 10 patients (47.6%) had type C. Based on Masaoka staging, 10 patients (47.6%) were stage II, 7 patients (33.3%) were stage III, and 4 patients (19.1%) were stage IVa. Three-dimensional RT was adminstered to the tumor volume (planned target volume), including the anterior mediastinum and the residual disease. The total RT dose ranged from 52.0 to 70.2 Gy (median dose, 54 Gy). Consistent with the WHO criteria, the response rate was only analyzed for the 6 patients who received a biopsy only. The prognostic factors analyzed for an estimate of survival included age, gender, tumor size, tumor pathology, Masaoka stage, the possibility of treatment by performing surgery, the presence of myasthenia gravis, and RT dose. Results: The 3-year overall survival rate (OS) and the progression free survival rate (PFS) were 80.7% and 78.2%, respectively. Among the 10 patients with WHO cell type C, 3 of 4 patients (75%) who underwent a complete resection and 3 of 6 patients (50%) who underwent a biopsy survived. Distant metastasis developed in 4 patients (19.1%). The overall response rate in the 6 patients who received biopsy only were as follows: partial remission in 4 patients (66.7%), stable disease in 1 patient (16.6%), and progressive disease in 1 patient (16.6%). Acute RTOG radiation pneumonitis occurred in 1 patient (4.8%), grade 2 occurred in 2 patients (9.5%), grade 3 occurred in 1 patient (4.8%), and grade 4 occurred in 1 patient (4.8%). A univariate analysis revealed that the significant prognostic factors for OS were age (${\geq}60$, 58.3%; <60, 100%; p=0.0194), pathology (WHO cell type A-B3, 100%; C, 58.3%; p=0.0194) and, whether the patient underwent surgery (yes, 93.3%; no, 50%; p=0.0096). Conclusion: For the 15 patients who received surgery, there was no local failure within the radiation field. In patients with WHO cell type C, surgical procedures could have resulted in a more favorable outcome than biopsy alone. We report here our clinical experience in 21 patients with thymoma who were treated by radiation therapy.

• Tuberculosis and Respiratory Diseases
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• v.71 no.6
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• pp.464-469
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• 2011

Adalimumab is a full human monoclonal antibody that inhibits tumor necrosis factor-alpha (TNF-${\alpha}$). This has recently been shown to be effective in the treatment of rheumatoid arthritis (RA), ankylosing spondylitis, and other conditions. Sacoidosis is known to be the target for adalimumab but we describe a patient who has developed sarcoidosis with lung involvement during adalimumab therapy for RA. A 48-year-old woman, who was treated with adalimumab for 5 months, was admitted because of chronic cough and both hilar lymphadenopathy on chest radiography. Chest computed tomography revealed the enlargement of multiple lymph nodes in the right supraclavicular, subcarinal, both hilar and right axillary area. She was diagnosed with sarcoidosis based on the biopsy of supraclavicular lymph node, skin and lung through video-associated thoracoscopic surgery, which was non-caseating epitheloid cell granuloma and excluded from a similar disease. She was treated for sarcoidosis with prednisolone and methotrexate instead of adalimumab.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1831-1835
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• 2014

Background: To investigate the relationship between extracellular matrix parameters and texture of prostatic lesions evaluated by transrectal real-time tissue elastography (TRTE). Methods: 120 patients suspicious for prostate cancer underwent TRTE. Targeted biopsies were carried out after 12-core systematic biopsy. Epithelia were stained with hematoxylin-eosin, and Victoria blue and Ponceau S were used to stain elastic-collagen fibers, and picric acid-sirius red for visualization of collagen type I (Col1) and III (Col3). Smooth muscles were visualized by immunohistochemistry. All image analyses were performed in a blind manner using Image Pro Plus 6.0, and the area ratios of epithelium, elastic fibers, collagen fibers and Col1/Col3 were determined. Results: 42 patients with typical elastograms were included in the final data analysis. Significant differences were detected between the benign and malignant groups in the area ratios of epithelium (P = 0.01), smooth muscles and Col1/Col3 (P = 0.04, P = 0.02, respectively). There were no significant differences in the area ratios of epithelium, smooth muscle and elastic fibers between the stiff and soft lesion groups. The area ratio of Col1 was ($0.05{\pm}0.03$) in the stiff group, and ($0.02{\pm}0.01$) in the soft group (P= 0.00). However, the area ratio of Col3 was ($0.03{\pm}0.02$) in the stiff group, and ($0.05{\pm}0.04$) in the soft group (P = 0.16). Col1/Col3 in the stiff group ($1.99{\pm}1.59$) was greater than in the soft group ($0.71{\pm}0.64$) (P = 0.01). Conclusions: Tissue hardness of prostatic tumors was mainly dependent on the Col1 content, Col1/Col3 being higher in malignant than in benign lesions, so the prostate tissue texture can be used as a target for distinguishing between the two with TRTE.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.2
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• pp.67-75
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• 2013

Objective: To investigate the effect of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPAR${\gamma}$ agonist). Results: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPAR${\gamma}$ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin $E_2$ production in the ESCs of endometriosis. Conclusion: This study suggests that PPAR${\gamma}$ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

• International journal of advanced smart convergence
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• v.8 no.1
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• pp.24-34
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• 2019

In this research, a practical deep learning framework to differentiate the lesions and nodules in breast acquired with ultrasound imaging has been proposed. 7408 ultrasound breast images of 5151 patient cases were collected. All cases were biopsy proven and lesions were semi-automatically segmented. To compensate for the shift caused in the segmentation, the boundaries of each lesion were drawn using Fully Convolutional Networks(FCN) segmentation method based on the radiologist's specified point. The data set consists of 4254 benign and 3154 malignant lesions. In 7408 ultrasound breast images, the number of training images is 6579, and the number of test images is 829. The margin between the boundary of each lesion and the boundary of the image itself varied for training image augmentation. The training images were augmented by varying the margin between the boundary of each lesion and the boundary of the image itself. The images were processed through histogram equalization, image cropping, and margin augmentation. The networks trained on the data with augmentation and the data without augmentation all had AUC over 0.95. The network exhibited about 90% accuracy, 0.86 sensitivity and 0.95 specificity. Although the proposed framework still requires to point to the location of the target ROI with the help of radiologists, the result of the suggested framework showed promising results. It supports human radiologist to give successful performance and helps to create a fluent diagnostic workflow that meets the fundamental purpose of CADx.

• Animal Bioscience
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• v.35 no.1
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• pp.22-28
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• 2022

Objective: Endoplasmic reticulum (ER) stress engages the unfolded protein response (UPR) that serves as an important mechanism for modulating hepatic fatty acid oxidation and lipogenesis. Chronic fasting in mice induced the UPR activation to regulate lipid metabolism. However, there is no direct evidence of whether negative energy balance (NEB) induces ER stress in the liver of cows. This study aimed to elucidate the relationship between the NEB attributed to feed deprivation and ER stress in bovine hepatocytes. Methods: Blood samples and liver biopsy tissues were collected from 6 non-lactating cows before and after their starvation for 48 h. The blood non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA) and glucose level were analyzed. Real-time quantitative polymerase chain reaction and Western blotting were used to explore the regulation of genes associated with UPR and lipid metabolism. Results: The starvation increased the plasma BHBA and NEFA levels and decreased the glucose level. Additionally, the starvation caused significant increases in the mRNA expression level of spliced X-box binding protein 1 (XBP1s) and the protein level of phosphorylated inositol-requiring kinase 1 alpha (p-IRE1α; an upstream protein of XBP1) in the liver. The mRNA expression levels of peroxisome proliferator-activated receptor alpha and its target fatty acid oxidation- and ketogenesis-related genes were significantly upregulated by the starvation-mediated NEB. Furthermore, we found that the mRNA expression levels of lipogenic genes were not significantly changed after starvation. Conclusion: These findings suggest that in the initial stage of NEB in dairy cows, the liver coordinates an adaptive response by activating the IRE1 arm of the UPR to enhance ketogenesis, thereby avoiding a fatty liver status.