Neurodegenerative diseases are characterized by distinct protein aggregates, such as those of α-synuclein and tau. Lysosomal defect is a key contributor to the accumulation and propagation of aberrant protein aggregates in these diseases. The discoveries of common proteinopathies in multiple forms of lysosomal storage diseases (LSDs) and the identification of some LSD genes as susceptible genes for those proteinopathies suggest causative links between LSDs and the proteinopathies. The present study hypothesized that defects in lysosomal genes will differentially affect the propagation of α-synuclein and tau proteins, thereby determining the progression of a specific proteinopathy. We established an imaging-based high-contents screening (HCS) system in Caenorhabditis elegans (C. elegans) model, by which the propagation of α-synuclein or tau is measured by fluorescence intensity. Using this system, we performed RNA interference (RNAi) screening to induce a wide range of lysosomal malfunction through knock down of 79 LSD genes, and to obtain the candidate genes with significant change in protein propagation. While some LSD genes commonly affected both α-synuclein and tau propagation, our study identified the distinct sets of LSD genes that differentially regulate the propagation of either α-synuclein or tau. The specificity and efficacy of these LSD genes were retained in the disease-related phenotypes, such as pharyngeal pumping behavior and life span. This study suggests that distinct lysosomal genes differentially regulate the propagation of α-synuclein and tau, and offer a steppingstone to understanding disease specificity.
Dong Chul Lee;Ho Hyung Lee;Sung Hoon Koh;Jin Soo Kim;Si Young Roh;Kyung Jin Lee
Archives of Plastic Surgery
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v.51
no.1
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pp.94-101
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2024
Background For the small glabrous skin defect, Thenar and Hypothenar skin are useful donors and they have been used as a free flap. Because of similar skin characteristics, both flaps have same indications. We will conduct comparative study for the donor morbidity of the Free thenar flap and Hypothenar free flap. Methods From January 2011 to December 2021, demographic data, characteristics of each flap, and complications using retrospective chart review were obtained. Donor outcomes of the patient, who had been followed up for more than 6 months, were measured using photographic analysis and physical examination. General pain was assessed by Numeric Rating Scale (NRS) score, neuropathic pain was assessed by Douleur Neuropathique 4 Questions (DN4) score, scar appearance was assessed by modified Vancouver Scar Scale (mVSS), and patient satisfaction was assessed on a 3-point scale. Statistical analysis was performed on the outcomes. Results Out of the 39 survey respondents, 17 patients received Free thenar flaps, and 22 patients received Hypothenar free flaps. Thenar group had higher NRS, DN4, and mVSS (p < 0.05). The average scores for the Thenar and Hypothenar groups were 1.35 and 0.27 for NRS, 2.41 and 0.55 for DN4, and 3.12 and 1.59 for mVSS, respectively. Despite the Hypothenar group showing greater satisfaction on the 3-point scale (1.82) compared with the Thenar group (1.47), the difference was not significant (p = 0.085). Linear regression analysis indicated that flap width did not have a notable impact on the outcome measures, and multiple linear regression analysis revealed no significant interaction between flap width and each of the outcome measures. Conclusion Despite the limited number of participants, higher donor morbidity in general pain, neuropathic pain, and scar formation was noted in the Thenar free flap compared with the Hypothenar free flap. However, no difference in overall patient satisfaction was found between the two groups.
Journal of Dental Rehabilitation and Applied Science
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v.39
no.4
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pp.229-236
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2023
Maxillary bone defects may follow surgical treatment of benign and malignant tumors, trauma, and infection. Palatal defects often lead to problems with swallowing and pronunciation from the leakage of air into the nasal cavity and sinus. Obturators have been commonly used to solve these problems, but long-term use of the device may cause irritation of the oral mucosa or damage to the abutment teeth. Utilizing implants in the edentulous area for the fabrication of the obturators has gained attention. This case report describes a patient, who had undergone partial resection of the maxilla due to adenocarcinoma, in need of a new obturator after losing abutment teeth after long-term use of the previous obturator. Implants were placed in strategic locations, and an implant-retained maxillary obturator was fabricated, showing satisfactory results in the rehabilitation of multiple aspects, including palatal defect, masticatory function, swallowing, pronunciation, and aesthetics.
Background The anterolateral thigh (ALT) flap is a preferred option in the reconstruction of a wide variety of defects, enabling multiple tissue components and thicknesses. Methods This study was conducted to investigate the correlation of the thickness of the traditional subfascial ALT flap and superficial fat flap with age, gender, and body mass index (BMI). A total of 42 patients (28 males and 14 females) were included in the study. Results Mean age was 50.2 (range, 16-75) years and mean BMI was 24.68 ± 4.02 (range, 16.5-34.7) kg/m2. The subfascial flap thickness was significantly thinner in male patients (16.07 ± 2.77 mm) than in female patients (24.07 ± 3.93 mm; p < 0.05), whereas no significant difference was found between male (4.28 ± 1.15 mm) and female patients (4.85 ± 1.09 mm) regarding superficial fat flap thickness (p = 0.13). The thickness of both flaps had a positive correlation with BMI, and the strongest correlation was found for subfascial ALT thickness in female patients (r = 0.81). Age had no effect on both flap thickness measurements. The anterior thigh is thicker in women than in men, although it varies according to BMI. This shows that flap elevation is important in the superthin plane, especially if a thin flap is desired in female patients in defect reconstruction with the ALT flap. Thus, a single-stage reconstruction is achieved without the need for a defatting procedure after subfascial dissection or a second defatting procedure 3 to 6 months later. Conclusion The appropriate ALT flap plane should be selected considering the gender and BMI of the patient.
The Journal of Korea Assosiation for Disability and Oral Health
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v.12
no.1
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pp.6-10
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2016
Esophageal atresia is the abnormal development of the esophagus that connects the mouth to the stomach. This birth defect results in the incomplete connection of the esophagus to the stomach causing an inability to swallow properly and breathing difficulties. Surgery is the only treatment for esophageal atresia. Patients undergone an esophageal reconstruction usually suffer from gastroesophageal reflex. A 5-year old boy with congenital esophageal atresia and Sciwitar syndrome visited Seoul National University Dental Hospital because generalized excessive loss of tooth structure. The patient had history of multiple operations for reconstruct esophagus. He had little food intake experience thought oral and had difficulty to swallowing. The patient was generalized severe erosive and decayed state. For patient, the dental procedure under general anesthesia was scheduled due to the multiple caries with erosion and poor cooperation. Under general anesthesia, pulpectomy and restoration as well as extraction was performed. Gastroesophageal reflex is potentially serious condition, with various extraesophageal adverse effects such as dental erosion. To prevent progression of dental caries, dietary counselling and oral hygiene instruction should be reinforced. Also, restorations to erosive teeth will maintain esthetics and function and preserve pulp vitality.
It is known that low birth weight is a risk factor for poor outcome in cardiac surgery for many cardiac defects. We reviewed our recent surgical experiences on congenital heart defect (other than patent ductus arteriosus) in low birth weight babies. Material and Method: From September 1994 to February 2001, 31 consecutive infants weighing 2500 g or less underwent cardiac surgery with (OHS group n=12) or without cardiopulmonary bypass (CHS group n=19). A retrospective study was carried out to evaluate short-and intermediate-term outcome. Mean gestational age and age at operation were 36.9 weeks(range, 32.3-42weeks) and 32.1days (range, 0-87days) respectively. Mean body weight at birth and operation were 1972g (range, 1100-2500g) and 2105g (range, 1450-2500 g) respectively. There was no difference between the two groups in age and body weight. Defects included ventricular septal defect (VSD) (n=3), VSD with arch anomaly (n=2), total anomalous pulmonary venous return (n=2), transposition of the great arteries (TGA) (n=2), truncus arteriosus (n=2), and univentricular heart with cor triatriatum (n=1) in OHS group, and coarctation of aorta (n=7), tetralogy of Fallot (TOF) (n=3), TOF with pulmonary atresia (n=3), multiple muscular VSDs (n=1), double outlet right ventricle (n=1), pulmonary atresia with intact ventricular septum (n=2), tricuspid atresia (n=1), and TGA with multiple VSD (n=1) in CHS group. 13 patients (41.9%) were intubated pre-operatively. Result: There were 4 early deaths(<30 days); 1 (8.3%) in OHS group and 3 (15.8%) in non-OHS group. All these early deaths were related to the pulmonary artery banding(PAB). There was no operative mortality in infants undergoing complete repair and palliative operations other than PAB. Delayed sternal closure was required in 3 patients. Prolonged postoperative mechanical ventilation (>7 days) was required in 7 patients(58.3%) in OHS and 7(38.8%) in CHS group. Late mortality occurred in 3 patients, two of which were non-cardiac. A patient in OHS group was documented to have neurologic sequelae. All the survivors except two are in NYHA class 1. Conclusion: Complete repair and palliative operations other than PAB can be performed in low birth weight infants with low operative mortality and an acceptable intermediate-term result. However, about a half of the patients required long-term postoperative mechanical ventilation.
Purpose: The aim of this study was to evaluate the effect of immobilization of the recombinant human bone morphogenetic protein 2 (rhBMP-2) on anodized titaum implants coated with heparin to enhance the vertical alveolar ridge augmentation in the supraalveolar peri-implant defect region. Materials and methods: 18 pure titanium implants (7.0 mm in length, 3.5 mm in diameter) were manufactured for this study. All implants were anodized and designed insertion reference line marked with laser at the apical 2.5 mm from the fixture platform. Implantation of 6 noncoated anodized implants (Control group), 6 anodized implants physically adsorbed with rhBMP-2 by dip and dry method (BMP group) and 6 anodized implants chemically immobilized 3,4-dihydroxyphenylalanine (DOPA)-heparin/ rhBMP-2 (Hep-BMP group) was performed in the both mandibular of three male adult beagle dogs using split-mouth design. Radiologic examinations were performed immediately after implant placement and 4 and 8 weeks after implant placement. The amount of mesio-distal bone augmentation was evaluated by measuring the vertical distance from the platform to the marginal bone. Statistical analysis was performed using one-way analysis of variance (SPSS version 18.0) and multiple comparison analysis of The Kruskal-Wallis test and the Mann-Whitney U test. Statistical significance was established at the 5% significant level. Results: At the 4 weeks vertical alveolar ridge augmentation of Control group, BMP group and Hep-BMP group is $0.09{\pm}0.22mm$, $1.02{\pm}0.72mm$, and $1.29{\pm}0.51mm$, At the 8 weeks $0.11{\pm}1.26mm$, $1.11{\pm}0.58mm$, $1.59{\pm}0.79mm$ according to radiographic observations. The two experimental groups showed a significantly increasing in vertical bone height compared with the control group (P<.05). However, there is no significant difference between the BMP group and Hep-BMP group (P>.05). Conclusion: The rhBMP-2 coated implants were enhanced the vertical bone growth in the supraalveolar peri-implant defect area. However, there is no significant difference between chemically and physically coating method.
Park, Su Jin;Ahn, Moon Bae;Jang, Woori;Cho, Won Kyung;Chae, Hyo Jin;Kim, Myung Shin;Suh, Byung Kyu
Journal of The Korean Society of Inherited Metabolic disease
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v.17
no.3
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pp.103-108
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2017
Kabuki syndrome is a rare congenital disorder that causes multiple birth defects and mental retardation. Mutation of the lysine methyltransferase 2D (KMT2D) gene is the primary cause of Kabuki syndrome. We report a 4-year-old Korean girl diagnosed with Kabuki syndrome based on distinctive facial features (eversion of the lower lateral eyelid, arched eyebrows, depressed nasal tip, prominent ears), skeletal anomalies, short stature, and molecular analysis, which revealed a novel frameshift mutation in the KMT2D gene. A 4-year-old patient had a past history of congenital cardiac malformations (coarctation of the aorta, ventricular septal defect, atrial septal defect, patent ductus arteriosus), subclinical hypothyroidism and dysmorphic features at birth including webbed neck, short fingers, high arched palate, micrognathia and horseshoe kidney. She showed unique facial features such as a long palpebral fissure, long eyelashes, arched eyebrows with sparseness of the lateral third, broad nasal root, anteverted ears, and small mouth. Her facial features suggested Kabuki syndrome, and genetic analysis discovered a novel heterozygous frameshift mutation (c.4379dup, p.Leu1461Thrfs*30) in exon 15 of the KMT2D gene. The diagnosis of our 4-year-old patient was made through thorough physical examination and history taking, and genetic testing. It is challenging to diagnose patients with Kabuki syndrome at birth, since the characteristic facial features are expressed gradually during growth. Clinical suspicion aroused by regular follow-ups may lead to earlier diagnosis and interventions.
Kim, Il-Kyu;Park, Jong-Won;Lee, Eon-Hwa;Yang, Jung-Eun;Chang, Jae-Won;Pyun, Yeong-Hun;Ju, Sang-Hyun;Wang, Boon
Maxillofacial Plastic and Reconstructive Surgery
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v.32
no.5
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pp.447-453
/
2010
The hemifacial microsomia is characterized by variable underdevelopment of the craniofacial skeleton, external ear, and facial soft tissues. So, patients with hemifacial microsomia have an occlusal plane canting and malocclusion with facial asymmetry. Distraction osteogenesis (DO) with an intraoral or extraoral device is a technique using tension to generate new bone with gradual bone movement and remodeling. DO has especially been used to correct craniofacial deformities such as a hemifacial microsomia, facial asymmetry, and mandible defect that could not adequately be treated by conventional reconstruction with osteotomies. It has a significant advantage to lengthen soft and hard tissue of underdeveloped site without bone graft and a few complication such as nerve injury or muscle contracture. A 13-years old girl visited our clinic for the chief complaint of facial asymmetry. She had a left hypoplastic maxilla and mandible, occlusal plane canting and malocclusion. We diagnosed hemifacial microsomia and lanned DO to lengthen the affected side. Le Fort I osteotomy, left mandibular ramus and symphysis osteotomy were performed. The internal distraction devices fixed with screw on maxillary and mandibular ramus osteotomy sites. External devices were adapted to lower jaw for DO on symphysis osteotomy site and to upper jaw for rapid maxillary expansion (RME). At 7days after surgery, distraction was started at the rate of 1mm per day for 13days, and after 4months consolidation periods, distraction devices were removed. Simultaneous multiple maxillo-mandibular distraction osteogenesis with RME resulted in a satisfactory success in correcting facial asymmetry as well as occlusal plane canting for our hemifacial microsomia.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.36
no.6
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pp.460-465
/
2010
Introduction: A cleft palate is a common birth defect in humans with an incidence of 1/500 to 1/1,000 births. It appears to be caused by multiple genetic and environmental factors during palatogenesis. Many molecules are involved in palate formation but the biological mechanisms underlying the normal palate formation and cleft palate are unclear. Accumulating evidence suggests that transforming growth factor $\beta$/bone morphogenetic proteins (TGF-$\beta$/BMP) family members mediate the epithelial-mesenchymal interactions during palate formation. However, their roles in palatal morphogenesis are not completely understood. Materials and Methods: To understand the roles of TGF-$\beta$/BMP signaling in vivo during palatogenesis, mice with a palatal mesenchyme- specific deletion of Smad4, a key intracellular mediator of TGF-$\beta$/BMP signaling, were generated and analyzed using the Osr2Ires-Cre mice. Results: The mutant mice were alive at the time of birth with open eyelids and complete cleft palate but died within 24 hours after birth. In skeletal preparation, the horizontal processes of the palatine bones in mutants were not formed and resulted in a complete cleft palate. At E13.5, the palatal shelves of the mutants were growing as normally as those of theirwild type littermates. However, the palatal shelves of the mutants were not elevated at E14.5 in contrast to the elevated palatal shelves of the wild type mice. At E15.5, the palatal shelves of the mutants were elevated over the tongue but did not come in contact with each other, resulting in a cleft palate. Conclusion: These results suggest that mesenchymal Smad4 mediated signaling is essential for the growth of palatal processes and suggests that TGF-$\beta$/BMP family members are essential regulators during palate development.
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