Effects of Mycophenolic Acid and Rapamycin on Toll-Like Receptor Expression in Hypoxic Human Proximal Tubular Epithelial Cells

Background: Toll like receptor (TLR), an element of innate immunity, is upregulated by Ischemia/reperfusion (IR) injury and may be involved in adaptive immune response. Immunosuppressive agents may increase or attenuate IR injury and TLR expression. To explore the involvement of TLRs in hypoxic tubular injury and modification by mycophenolic acid (MPA) rapamycin (RAP), this study examined TLR expression in hypoxia-induced human renal proximal tubular epithelial cells (HK-2). Methods: HK-2 cells were cultured in keratinocyte-SFM media supplemented with epidermal growth factor and bovine pituitary extract. The Induction of hypoxia was achieved using GasPak pouch system. TLR 2, 3, and 4 mRNA expression was analyzed by real time RT-PCR using SYBR green and TLR 4 protein expression was evaluated by Western blot analysis. MPA at concentration of 100 nM and 1uM and RAP at concentration of 20, 50, and 100 nM were added to culture medium. Results: TLR4 but noTLR2 or TLR3 mRNA expressions increased in hypoxic HK-2 cells at 24 and 48 hrs. TLR4 protein expression also increased in hypoxic HK-2 cells at 24 and 48 hrs. MPA (100 nM and 1uM) and RAP (20, 50, and 100 nM) decreased hypoxia-induced TLR4 mRNA expression in HK-2 cells compared to normoxia at 24 hrs. However, TLR4 protein expression was decreased only by RAP at 20 and 50 nM. Conclusions: The results suggest that RAP may modify hypoxic renal tubular damage by decreasing TLR4-mediated inflammatory and immune reactionsope

Effect of Modification of Immunosuppressive Regimen on Renal Allograft Survival Rate in Recipients with Mild Chronic Rejection

Purpose: Concept that modification of immunosuppression can delay the deterioration of graft function and graft failure is the one of strategies for chronic rejection. We analyzed the effect of modification of immunosuppression in 116 recipients with biopsy confirmed mild chronic rejection retrospectively. Methods: Mild chronic rejection was diagnosed by single renal pathologist under the uniformed criteria; mild tubular atrophy & interstitial fibrosis (less than 25%) combined with vascular change such as fibrous intimal thickening. General rules of modification after chronic rejection in our center were (1) strict adjustment of cyclosporine (CsA) dosage around 100~120㎍/L of trough blood level, (2) triple conversion in double therapy recipients (add anti-metabolites; azathioprine or MMF), (3) dose increment of anti-metabolites, (4) maintain of immunosuppression if ongoing immunosuppression is satisfactory to above criteria. Results: After 74.8±44.5 months of follow-up, we identified 72 graft failures (62.1%). Overall post-diagnosis graft survival rate were 93.1%, 79.7%, 63.6% and 35.8% in 1, 3, 5 and 10 years respectively. The status of graft function categorized by stage of chronic kidney disease (CKD) at diagnosis (CKD 4 or 5 stage), timing of diagnosis (more than post-transplant 3 years) and presence of severe proteinuria (more than 1g/day of urinary excretion) were significant risk factors affecting the post-diagnosis graft survival rate. In multivariate survival analysis, these factors were confirmed as independent variables affecting post-diagnosis graft survival rate. But modification of immunosuppressive regimen after mild chronic rejection which was classified by modification (yes versus no), type of anti-metabolites (azathioprine versus MMF) and change of immunosuppressive strength (equal versus additional versus incremental) didn`t cause the significant difference of post-diagnosis graft survival rate. Conclusion: Though pathologic change is mild, the modification of immunosuppression is not effective to delay graft failure in renal allograft recipient with pathologically established chronic rejection.ope

Immunologic Control for Polyomavirus Infection after Kidney Transplantation

Purpose: The purposes of this study were to compare the relative efficacy of urine decoy cell (UDC) and polymerase chain reaction (PCR) for the polyomavirus infection (PVI), and to search the efficacy of preemptive immunologic control for PVI in earlier stage before irreversible graft injury. Methods: Between Mar. 2003 to Sep. 2005, 265 patients were monitored for the PVI after kidney transplantation. Of the 265 patients, the results of preemptive immunologic modifications were searched among 222 recipients who had the complete data. Results: Of the total 222 patients, 75 patients (33.8%) were positive for UDCs in at least one examination. Overall cumulative incidence of PVI was 32.9%. According to the episode of acute rejection, the one year incidences of PVI were 51.4% and 29.5% in recipients with and without the episode of acute rejection, respectively (P=0.0047). Using decoy cells as a marker of PV viruria, cytology has a sensitivity of 57.1% and negative predictive value of 74.1%. The specificity and positive predictive value for viruria (not viral nephropathy) are 67.2% and 48.8%. False-negative results occurred in samples with suboptimal cellularity, and a low viral load. Three cases of PV nephropathy (PVN) were documented. From January 2001 to December 2002, when we did not prospectively monitor UDCs, 7 cases of PVN were documented among the 116 recipients. Conclusion: The combination test of UDC and PV PCR should be considered as screening test for PVI due to low positive predictive value of UDC. The modulation of net immunosuppression based on UDC values and PV viral loads may reduce the development of PVN.ope

A re-evaluation of the renal ablation model of progressive renal disease in rats

BACKGROUND: The remnant kidney model, usually involving sudden removal or ablation of 1- 1 / (2) to 1-5 / (6) of renal mass, results in compensatory hypertrophy followed by hypertension, proteinuria and declining glomerular filtration rate (GFR) associated with focal (FSG) and then global glomerulosclerosis (GS) and tubulointerstitial injury (TI). Since most renal diseases involve much more gradual injury, we asked whether slow ablation (SA) produced a different natural history than fast ablation (FA). METHODS: Male Münich-Wistar rats underwent heminephrectomy, 3 weeks later a second, and 3 weeks later a third heminephrectomy (SA). They were compared to littermates undergoing simultaneous removal of 1- 1 / (2) kidneys (FA) and sham operated controls (C). RESULTS: Three weeks after the second heminephrectomy, the SA rats had no FSG and glomerular volume (GV) was similar to that of FA rat renal tissue removed at that time. Eight weeks following the final surgical procedure (FSP), the SA and FA groups had similar blood pressures (BP) but higher than C. Albumin excretion rates (AER) were higher in SA and FA vs. C at 1 month after the FSP and, throughout most of the subsequent 5 months, greater in the SA vs. FA groups. At 24 weeks, cortical interstitial fractional volume was double C values in both the SA and FA groups. Percentage of glomeruli with FSG and size (score) of FSG lesions was much higher in SA and FA than C. Moreover, the percentage of FSG in SA (61.2+/-16%) and FSG score (1.7+/-0.7) was greater than in FA animals (35.6+/-11.9% and 0.9+/-0.4, p<0.01 for each comparison). Mean GV, increased at 24 weeks in both groups over C (1.4+/-0.2 X 10(6) micro m(3)) was greater in SA (3.4+/-0.7 X 10(6) micro m(3)) than FA rats (2.1+/-0.4 X 10(6) micro m(3); p<0.005). CONCLUSIONS: The gradual uninephrectomy in the SA group, insufficient per se to produce significant renal damage, preconditioned the residual kidney, upon further removal of another 1 / (2) kidney, to more albuminuria and FSG lesions than occurred following sudden 1- 1 / (2) nephrectomy, despite similarly elevated BP. Perhaps more time for glomerular enlargement in the SA group preconditioned the remnant kidney to accelerated injury.ope

Chronic Cyclosporine Nephrotoxicity in Idiopathic Nephrotic Syndrome of Childhood

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Diagnosis of Renal Transplant Rejection: Banff Classification and Beyond

Diagnosis of renal transplant rejection is dependent on interpretation of renal allograft biopsies. The Banff Classification of Allograft Pathology, which was developed as a standardized working classification system in 1991, has contributed to the standardization of definitions for histologic injuries resulting from renal allograft rejections and provided a universal grading system for assessing these injuries. It has also helped to provide insight into the underlying pathogenic mechanisms that contribute to transplant rejection. In addition to histological and immunologic parameters, molecular tools are now being used to facilitate the diagnosis of rejection. In this review, I will discuss morphologic features of renal transplant rejections as well as major revisions and pitfalls of the Banff classification system, and provide future perspectives.ope

수직 벽 근처에서 상승하는 크기가 크고 변형가능한 기포의 움직임에 대한 실험적 연구

학위논문 (석사)-- 서울대학교 대학원 : 기계항공공학부, 2015. 2. 박형민.In the present study, the freely rising bubble behaviour near the vertical wall has been measured and analyzed while varying the wall configurations such as the initial distance between the bubble center and the wall and the wall material. The bubble Reynolds and Weber numbers are about 1100 and 4.4, respectively, based on the equivalent bubble diameter and these are relatively high values compared to those in the previous studies. The current bubble which has wobbling shape originally rises with a zig-zag trajectory indicating the two-dimensional movements. The initial distance between the bubble and the wall, and the surface boundary condition of the wall (no-slip, hydrophobic and porous, etc.) are considered to investigate the wall effect on the bubble motion. Though the bubble rises in the vicinity of the wall, the maintenance of two-dimensionality of the bubble rising path is confirmed while it is varied widely as bouncing, sliding and departing. In rising bubble motion, especially, the surface boundary condition significantly affects the bubble behaviour. So, first we analyze the rebounding motion of the bubble fitting with the sinusoidal function and apply the relation between the energy components with the bubble motion. The energy dissipation shows different trends according to the initial distance and wall boundary conditions. The hydrophobic condition causes larger amount of energy dissipation than no-slip condition when the bubble slides on the wall and as s/req increases (non-colliding motion appears), the dissipation has rather smaller value compared to no-slip condition. However, for the porous wall, the energy dissipation value is smallest among all conditions. Also, to deeply investigate the energy dissipation, the coefficient of restitution is calculated showing a good correlation with the variation of the energy components.Abstract Contents List of Figures Nomenclature Chapter 1 Introduction 2 Experimental setup and procedure 2.1 Experimental setup 2.2 Image processing 3 Results and Discussion 3.1 Rebounding bubble (s* < 2.0) 3.2 Sliding bubble (s* < 2.0) 3.3 Non-colliding bubble (s* > 2.0) 3.4 Mean and instantaneous rise velocities 3.5 Bubble orientation 3.6 Variation in the energy components 3.7 Coefficient of restitution 4 Summary and Conclusion BibliographyMaste

Podocytopathy and Morphologic Changes in Focal Segmental Glomerulosclerosis

Podocytopathy is glomerular lesions characterized by podocyte injury. It is observed in various glomerular diseases, but minimal change disease and focal segmental glomerulosclerosis (FSGS) are the prototypes. In this review, morphologic features of podocyte injury and subtypes of FSGS will be reviewed briefly. Effacement of podocyte foot processes is the most common feature of podocyte injury. As podocytic injury progresses, intracytoplasmic vacuoles, subpodocytic cyst, detachment of podocytes from the glomerular basement membrane and apoptosis develop. Glomerular capillary loops in epithelium-denuded area undergo capillary collapse. Synechia and hyalinosis may accompany this lesion. To manifest segmental sclerosis, podocyte loss above a threshold level may be required. Injured podocytes can injure neighboring intact podocytes, and thereby spread injury within the same lobule. FSGS can be categorized into five subtypes by morphologic characteristics; not otherwise specified (NOS), perihilar, cellular, tip, and collapsing types. Each subtype has been reported to show different clinical courses and associated conditions, but there are controversies on its significance. With recent progress in the discovery of genetic abnormalities causing FSGS and plasma permeability factors, we expect to unravel pathophysiology of FSGS and to understand histological sequences leading to FSGS in near future.ope

Is C1q Nephropathy a Distinct Disease Entity?

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한국 중학교 학생들의 문법학습에서의 중재의 역할: 사례연구구

학위논문 (석사)-- 서울대학교 대학원 사범대학 외국어교육과(영어전공), 2017. 8. 소영순.This study explored two cases of Korean middle school students who participated in DA (Dynamic Assessment) in teaching grammar. Two middle school students from Seoul were chosen as participants based on their English proficiency and a lack of over-seas study experience. The study employed a qualitative approach to get an in-depth ex-amination of the two students syntactic development of target forms. The methods of data collection used were picture description tasks. First, students were asked to write a paragraph describing the given pictures, using grammatical structures that were found to be problematic for them. Then, the mediator read their writing to detect any errors and provided mediation based on a mediation scale in order to lead the student to correct their errors. After each individual session with the students, the mediator transcribed the recording of the session and drew Language-Related Experiences. The findings of the study are 1) the frequency of the mediation scale varied2) students English proficiency levels and the nature of target forms influenced the effectiveness of the mediation3) students used their first and second languages as mediational tools, relying on different modes of language with varying portions4) the teacher played a crucial role in imple-menting DA as the mediator. Based on the aforementioned findings, the following peda-gogical implications were drawn: 1) mediation has a pedagogical impact on enhancing students linguistic development2) real-world constraints should be overcome to im-plement DA in the Korean context3) DA can be a tool to develop teacher expertise.CHAPTER 1. INTRODUCTION 1 1.1. Background and Purpose of the Study 1 1.2. Research Questions 5 1.3. Organization of the Thesis 5 CHAPTER 2.LITERATURE REVIEW 7 2.1. Dynamic Assessment in Language Learning 7 2.1.1. Dynamic Assessment in Second Language Learning 7 2.1.2. Dynamic Assessment in Teaching Grammar 9 2.1.3. Dynamic Assessment in Korean Context 12 2.2. Mediation in Dynamic Assessment 14 2.2.1. Traditional approach to feedback 14 2.2.2. Feedback in the Sociocultural approach 18 2.2.3. Mediation in DA 20 CHAPTER 3.METHODOLOGY 28 3.1. Participants 28 3.1.1. Student A 28 3.1.2. Student B 29 3.2. Instruments 30 3.2.1. Picture-description task 30 3.2.2. Mediation Scale 31 3.3. Procedures 33 3.3.1. Research Design 33 3.3.2. Pre-Test 35 3.3.3. Target forms 36 3.3.4. DA program 37 3.3.5. Post-Test 38 3.3.6. Posterior Interview 39 3.4. Data Analysis 39 CHAPTER 4. RESULTS 45 4.1. Student A: a talkative initiator 45 4.1.1. Learning Past Tense 47 4.1.2. Learning Conjunctions 62 4.1.3. Posterior Interview 74 4.1.4. Summary of Student As development 75 4.2. Student B: A Silent, cautious learner 77 4.2.1. Learning Conjunctions 80 4.2.2. Learning Other Relevant Forms 90 4.2.3. Posterior Interview 100 4.2.4. Summary of Student Bs development 103 4.3. The effect of mediation scale on grammar learning of two target forms 107 CHAPTER 5.DISCUSSION 116 5.1. Language as the tool for mediation 116 5.2. The role of the teacher in dynamic assessment 117 CHAPTER 6.CONCLUSION 120 6.1. Major Findings 120 6.2. Implications 121 6.3. Limitation and Suggestions for Further Research 123 REFERENCES 125 APPENDICES 136 국 문 초 록 164Maste