Modeling of Human Genetic Diseases Via Cellular Reprogramming

The generation of induced pluripotent stem cells (iPSCs) derived from patients' somatic cells provides a new paradigm for studying human genetic diseases. Human iPSCs which have similar properties of human embryonic stem cells (hESCs) provide a powerful platform to recapitulate the disease-specific cell types by using various differentiation techniques. This promising technology has being realized the possibility to explore pathophysiology of many human genetic diseases at the molecular and cellular levels. Furthermore, disease-specific human iPSCs can also be used for patient-based drug screening and new drug discovery at the stage of the pre-clinical test in vitro. In this review, we summarized the concept and history of cellular reprogramming or iPSC generation and highlight recent progresses for disease modeling using patient-specific iPSCs.

Modeling of Human Genetic Diseases Via Cellular Reprogramming

The generation of induced pluripotent stem cells (iPSCs) derived from patients' somatic cells provides a new paradigm for studying human genetic diseases. Human iPSCs which have similar properties of human embryonic stem cells (hESCs) provide a powerful platform to recapitulate the disease-specific cell types by using various differentiation techniques. This promising technology has being realized the possibility to explore pathophysiology of many human genetic diseases at the molecular and cellular levels. Furthermore, disease-specific human iPSCs can also be used for patient-based drug screening and new drug discovery at the stage of the pre-clinical test in vitro. In this review, we summarized the concept and history of cellular reprogramming or iPSC generation and highlight recent progresses for disease modeling using patient-specific iPSCs.

Apoptotic Cells and the Histopathologic Findings in Rotator Cuff Tears / 대한정형외과학회잡지

PURPOSE: We analyzed the relationship between the size of the torn rotator cuff and the frequency of finding apoptotic cells (apoptotic index) or pathological degeneration in the rotator cuff. MATERIALS AND METHODS: The edges of torn supraspinatus tendons were obtained from patients with rotator cuff tear (n=63). The study group consisted of 2 small, 22 medium, 22 large and 17 massive tears. For the histopathologic evaluation, the H&E stained sections of the torn supraspinatus tendons were examined. Apoptosis was detected with TUNEL assay. We analyzed the relationships between the tear size and the pathologic findings or the apoptotic index. RESULTS: Significant differences could not be found for the fibroblast cellularity, thickening of the synovial lining and proliferation of blood vessels according to the size of the rotator cuff tear. All the specimens had apoptotic cells that were concentrated around the margin of the tear site. The apoptotic indexes according to the tear size were 58.50 for the small tears, 27.25 for the medium tears, 33.29 for the large tears and 31.96 for the massive tears. No significant correlation was found between the tear size and the apoptotic index. CONCLUSION: There were no significant differences in the apoptotic indices, the fibroblast cellularity, the thickening of the synovial lining and the proliferation of blood vessels according to the size of the rotator cuff tear, and there were no correlations between the apoptotic index and the histopathologic findings.

The Methods and Results of Revision Total Knee Arthroplasty / 대한정형외과학회잡지

PURPOSE: To suggest operative methods for revision total knee arthroplasty (TKA) according to the causes of revision surgery. MATERIALS AND METHODS: The operative methods of 70 revision total knee arthroplasties in 64 patients between December 1996 and December 2004 were analyzed according to the causes. The mean follow-up period was 65 months (25-120 months). The range of motion and Hospital for Special Surgery (HSS) score were used for the clinical evaluation and the scoring system of American Knee Society was used for the radiographic evaluation. RESULTS: The mean periods of revision surgery from the initial operation was 59 months (1 month-20 years). Posterior cruciate retaining prosthesis was used in 8 cases, posterior cruciate substituting prosthesis in 14 cases, and constrained type prosthesis in 48 cases. The extension stem was required in 51 cases, metal augmentation in 34 cases, and structural allograft in 15 cases for bone defect treatment and firm fixation. The average range of motion improved from 88.8o preoperatively to 105.8o at the final follow-up. HSS score also improved from 60.5 to 87.6 points. The complications after revision TKA were 3 infections (4.3%), 1 patellar dislocation (1.4%), and 1 polyethylene dislocation (1.4%). CONCLUSION: Constrained type prostheses were needed in many cases of revision TKA. Satisfactory results were obtained using an additional structural allograft, metal augmentation, and extension stem for bone defect treatment and firm fixation.

Manifestations of Foot Inflammation in Seronegative Spondyloarthropathy / 대한정형외과학회잡지

PURPOSE: To analyze variable inflammatory manifestations around the foot in the early stages of seronegative spondyloarthropathy. MATERIALS AND METHODS: Sixty patients, who visited the clinic for inflammatory lesions around the foot and were diagnosed with seronegative spondyloarthropathy, were included in this study. The cases were classified according to the main inflammatory lesions of the foot. Extra-skeletal lesions were also evaluated. RESULTS: Among the main inflammatory lesions of the foot, the most common lesions were insertional Achilles tendinitis and plantar fasciitis in 17 (28.3%) patients. Eleven (18.3%) cases were inflammation of the metatarsophalangeal joint or metatarsal head. Among the cases with multiple foot lesions, both insertional Achilles tendinitis and synovitis of the metatarsophalangeal joint were observed in 8 patients. Among the extra-foot lesions, back pain or synovitis of the knee joint were observed in 17 patients, and 8 cases had sacroilitis. In the patients with extra-skeletal lesions, psoriatic skin lesions were observed in 2 patients and uveitis in 1 patient. CONCLUSION: Due to its various and nonspecific manifestations, HLA-B27 related chronic inflammatory foot lesions have been easily overlooked and inappropriately treated. Therefore, particular attention should be paid to HLA-B27 positive cases that have waxing and waning of inflammatory foot lesions.