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Biomedical subjects

Yong Choi

Publications and source records attributed to Yong Choi.

At least 19 recordsLinked to original sources

Clinical outcomes of childhood lupus nephritis: a single center's experience.

This study retrospectively reviewed the medical records of children with lupus nephritis (LN) who were treated at Seoul National University Children's Hospital from 1986 to 2005 (mean duration 8.3+/-4.4 years). The records of 77 children (22 male and 55 female) were examined. The mean age at diagnosis was 11.9+/-3.0 years. The initial biopsy results revealed a WHO class IV classification for 60 (88.2%) of 68 biopsy proven cases. Of 77 patients, 67 (87.0%) responded initially to the high-dose corticosteroids with or without additional immunosuppressive therapy. Of the initial responders (67), 30 (44.8%) experienced at least one episode of proteinuric (24) or nephritic (6) flare. Thirteen patients (16.9%) progressed to either chronic renal failure (CRF) or end-stage renal disease (ESRD). Six (7.8%) patients died. A Kaplan-Meier estimate of patient survival and CRF-free survival rate was 95.4% and 88.7% at 5 years and 91.8% and 74.7% at 10 years, respectively. Multivariate analysis for class IV LN revealed male gender (P=0.029), initial hypertension (P=0.001) and absence of remission (P=0.002) to be prognostic factors predicting CRF. Glomerulosclerosis of 10% or more (P=0.005), nephritic flare (P=0.011), and presence of anti-phospholipid antibody (P=0.017) or syndrome (P=0.004) were also found to be independent risk factors for CRF. Cyclophosphamide pulse therapy failed to demonstrate superiority over other combined immunosuppressants used for the treatment of diffuse proliferative LN.

Adolescent↗

Pattern of double glomerulopathy in children.

Occasional case reports have been issued on children with double glomerulopathy, involving either the coexistence of two different glomerulopathies or superimposition of a second glomerulopathy onto a first. A retrospective clinicopathological review of 294 children who had received renal biopsies resulted in 9 (3.1%) being confirmed to have double glomerulopathy. Superimposed glomerulopathy was diagnosed by a second renal biopsy in two cases, and coexistence of two glomerulopathies was confirmed by single biopsy in seven. Original glomerulopathies were those with a chronic course, such as Alport syndrome, IgA nephropathy, relapsing minimal-change nephrotic syndrome, Frasier syndrome, and thin basement membrane nephropathy. The superimposing glomerulopathies were common types in children, such as postinfectious glomerulonephritis, IgA nephropathy, and Henoch-Schönlein nephritis. Thus, the pattern of double glomerulopathy was considered to be due to the chance occurrence of two different glomerulopathies without a common pathogenesis. Acute nephritic symptoms of superimposed glomerulopathies resolved almost completely during follow-up in most cases. Double glomerulopathies are not rare in children and may occur by chance alone in most cases. The possibility of superimposed glomerulopathy should be suspected if the clinical course of a glomerulopathy changes atypically. However, the long-term influence of a superimposed glomerulopathy on renal functional deterioration remains unclear.

Child↗

Primary focal segmental glomerular sclerosis in children: clinical course and prognosis.

To review the clinical course and identify prognostic factors, we retrospectively analyzed 92 children with steroid-resistant primary focal segmental glomerulosclerosis (FSGS). The mean age of onset was 80.4+/-42.4 months. The mean follow-up duration was 98.2+/-63.3 months. Eighty-five patients presented with nephrotic syndrome and seven presented with asymptomatic proteinuria. Thirty-three patients were initial responders to steroid treatment (late non-responders) and 59 were initial nonresponders. At last follow-up, 36 patients (39.1%) were in complete remission, and 29 (31.5%) progressed to chronic renal failure (CRF). Renal survival rates at 5, 10, and 15 years were 84, 64, and 53%, respectively. By morphological classification, there were tip variants (6.1%), collapsing variants (10.6%), cellular variants (1.5%), perihilar variants (9.1%), and NOS (not otherwise specified, 72.7%). Among the variants, there were no significant differences in age of onset, degree of proteinuria, response to treatment, or progression to CRF. Poor prognostic factors for CRF included: asymptomatic proteinuria at presentation, initial renal insufficiency, higher segmental sclerosis (%), severe tubulointerstitial change, initial nonresponse, and absence of remission. In the multivariate analysis, an increase in the initial serum creatinine and resistance to treatment were independent risk factors for CRF. A more prolonged use of corticosteroid therapy and early introduction of cyclosporin A (CsA) may improve the prognosis for primary FSGS in patients with initial steroid nonresponsiveness.

Adolescent↗

Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging.

Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo imaging of plaques and tangles would be beneficial for the early diagnosis of AD. It has been suggested that 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one (curcumin) may be responsible for low age-adjusted prevalence of AD in India. In the present study, eight novel derivatives of curcumin and 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one (dehydrozingerone) were synthesized and their binding affinities for beta-amyloid (Abeta) aggregates were measured. Of these ligands, fluoropropyl-substituted curcumin (8) showed the highest binding affinity (Ki=0.07 nM), and therefore, 8 was radiolabeled and evaluated as a potential probe for Abeta plaque imaging. Partition coefficient measurement and biodistribution in normal mice demonstrated that [18F]8 has a suitable lipophilicity and reasonable initial brain uptake. Metabolism studies also indicated that [18F]8 is metabolically stable in the brain. These results suggest that [18F]8 is a suitable radioligand for Abeta plaque imaging.

Amyloid↗

Idiopathic membranous nephropathy in children.

Idiopathic membranous nephropathy (MN) is a rare cause of asymptomatic proteinuria (AP) or nephrotic syndrome (NS) in childhood. To improve our understanding of its clinical course, we retrospectively reviewed 19 cases of idiopathic MN seen in our hospital over a period of 28.5 years, i.e., from January 1977 to July 2005. Eight patients (39%) had AP and 11 (61%) presented with NS. All eight AP patients achieved remission, regardless of treatment modality. Oral corticosteroid was given to all 11 NS patients, but only three of them responded to corticosteroid. Of the eight steroid non-responders, three achieved remissions with the addition of cyclosporine, and the five who were not administered additional immunosuppressive drugs had persistent NS. At the latest evaluation, all six NS patients that achieved remission remained free of proteinuria and had a normal renal function. Moreover, two of the 5 steroid non-responders showed persistent nephrotic-range proteinuria but a stable renal function. The remaining three steroid non-responders progressed into chronic renal insufficiency, and this progression was preceded by renal vein thrombosis (RVT) in two of the three patients. Presentation with NS (P=0.045) and the development of RVT (P=0.010) were identified as poor prognostic factors.

Adolescent↗

Prognostic significance of vascular endothelial growth factor expression and microvessel density in esophageal squamous cell carcinoma: comparison with positron emission tomography.

BACKGROUND: This study investigated whether the expression of vascular endothelial growth factor (VEGF) in a primary tumor and the intratumoral microvessel density (MVD) were independent prognostic factors in patients with an esophageal squamous cell carcinoma (SCC) in comparison with positron emission tomography (PET) by using (18)F-fluorodeoxyglucose (FDG) and stage. METHODS: Fifty-one patients with a newly diagnosed esophageal SCC who underwent preoperative FDG-PET and esophagectomy with intent to cure were enrolled in this study. The VEGF expression level, the intratumoral MVD, and the Ki-67 labeling index were evaluated by using immunohistochemical staining. Only significant variables in the univariate survival analysis were examined by multivariate survival analysis with the Cox proportional hazards model. RESULT: Cancer-related deaths occurred in 17 of 51 patients during the follow-up. Univariate survival analysis showed that the pathologic stage, pNM, maximum standardized uptake value of the primary tumor, tumor length on PET, number of PET-positive lymph nodes, PET stage, Ki-67 labeling index, intratumoral MVD, and the presence of VEGF expression were significant prognostic predictors for the overall survival. Multivariate analysis revealed that the pathologic stage, number of PET-positive nodes (0, 1, 2, or > or = 3), intratumoral MVD (cutoff, 60/mm(2)), and presence of VEGF expression were independent significant prognostic predictors for overall survival. CONCLUSION: In addition to the pathologic stage, the intratumoral MVD, the presence of VEGF expression, and the number of FDG-PET-positive nodes were independent prognostic predictors in patients with an esophageal SCC undergoing curative surgery.

Adult↗

Nephrotic syndrome in a child after umbilical-cord-blood transplantation.

We report a 12-year-old girl who developed nephrotic syndrome 6 months after umbilical-cord-blood transplantation (UCBT) for acute lymphoblastic leukemia (L2). In addition to nephrotic syndrome, she also showed autoimmune hemolytic anemia, thrombocytopenia and gastrointestinal symptoms. Since these symptoms were manifested during the course of tapering immunosuppressive agents, a diagnosis of chronic graft-versus-host disease (GVHD) was made. Findings from a kidney biopsy were compatible with minimal-change disease (MCD), and focal glomerular capillary thrombosis and mild tubular damage were also noted. She was treated with methylprednisolone pulse therapy followed by oral prednisolone. Proteinuria disappeared in 14 days. Gastrointestinal symptoms, anemia and thrombocytopenia were also corrected. This is a case report of nephrotic syndrome as a manifestation of chronic GVHD developed after stem-cell transplantation. A review of the cases reported in the literature is also made.

Adolescent↗

Nutcracker syndrome in children with gross haematuria: Doppler sonographic evaluation of the left renal vein.

BACKGROUND: Nutcracker syndrome is characterized by gross haematuria caused by left renal vein (LRV) entrapment. OBJECTIVE: To assess the role of LRV ultrasonography in the diagnosis of the nutcracker syndrome in children. MATERIALS AND METHODS: Twelve children (eight male, four female; mean age 12.8 years) with venographically confirmed nutcracker syndrome (LRV-IVC pressure gradient > or = 3 mm Hg) underwent LRV sonography including Doppler spectral analysis (n=7). The diameter and peak velocity (PV) were measured at two sites of the LRV (renal hilum and aortomesenteric portion). The US findings of nutcracker syndrome were compared with those of 20 control subjects using the t-test. We identified the optimal cut-off value of the US parameters for the diagnosis of the nutcracker syndrome using ROC analysis. RESULTS: The PV at the aortomesenteric portion and the ratio of the PV between the two measured points showed significant differences between the two groups (P<0.0001). The optimum cut-off values were found to be 4.7 for the PV ratio (sensitivity 100%, specificity 90%, accuracy 93%), and 93 cm/s for the PV at the aortomesenteric portion (sensitivity 100%, specificity 85%, accuracy 89%). CONCLUSION: LRV sonography, including Doppler spectral analysis, can demonstrate LRV entrapment haemodynamically.

Adolescent↗

Depressed heart rate response to vasodilator stress for myocardial SPECT predicts mortality in patients after myocardial infarction.

BACKGROUND: As heart rate (HR) response during vasodilator stress myocardial perfusion studies can be a marker of HR variability, we investigated its prognostic value in patients after myocardial infarction (MI). METHODS: Subjects were 147 survivors of MI who underwent vasodilator stress thallium-201 scintigraphy. HR response was measured as peak to basal (P/B) ratios during vasodilator infusion. End points for survival analysis were all-cause deaths, non-fatal recurrent MI, and soft events. RESULTS: HR response was significantly depressed in the post-MI patients compared to controls (p<0.0005). HR response correlated to LVEF (r=0.37, p<0.0001) and summed stress scores (r=-0.18, p<0.05), but not with antianginal medication. During 58+/-30 mo of follow-up, there were 15 deaths, 7 recurrent MI, and 11 soft events. Low HR response, old age, low LVEF, and high difference score were significant univariate risk factors for death. Multivariate analysis identified low HR response (p=0.03), high stress score (p=0.02), and low LVEF (p=0.05) as independent predictors of mortality. The predictive value of HR response was incremental to that offered by other variables (p=0.02). CONCLUSIONS: HR response, readily attained during vasodilator stress myocardial perfusion studies, may provide useful additional prognostic information in post-MI patients.

Analysis of Variance↗

The defined combination of growth factors controls generation of long-term-replicating islet progenitor-like cells from cultures of adult mouse pancreas.

Application of pancreatic islet transplantation to treatment of diabetes is severely hampered by the inadequate islet supply. This problem could in principle be overcome by generating islet cells from adult pancreas in vitro. Although it is possible to obtain replicating cells from cultures of adult pancreas, these cells, when significantly expanded in vitro, progressively lose pancreatic-specific gene expression, including that of a "master" homeobox transcription factor Pdx1. Here we show for the first time that long-term proliferating islet progenitor-like cells (IPLCs) stably expressing high levels of Pdx1 and other genes that control early pancreatic development can be derived from cultures of adult mouse pancreas under serum-free defined culture conditions. Moreover, we show that cells derived thus can be maintained in continuous culture for at least 6 months without any substantial loss of early pancreatic phenotype. Upon growth factor withdrawal, the IPLCs organize into cell clusters and undergo endocrine differentiation of various degrees in a line-dependent manner. We propose that our experimental strategy will provide a framework for developing efficient approaches for ex vivo expansion of islet cell mass.

Animals↗

Is subnanomolar binding affinity required for the in vivo imaging of acetylcholinesterase? Studies on 18F-labeled G379.

Acetylcholinesterase (AChE) is an important cholinergic marker of Alzheimer's disease (AD) and shows reduced activity in postmortem AD brain tissues. 1-(4-Fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-fluoro-2-yl)methyl]piperidine (G379, ), an AChE inhibitor with a subnanomolar IC(50) (0.56 nM), was prepared as a (18)F-labeled radioligand ([(18)F]) and evaluated in mice. Metabolism studies of [(18)F] showed no metabolites in the mouse brain. Tissue distribution studies demonstrated its uniform regional distribution in the mouse brain, suggesting that this radioligand is not suitable for the in vivo imaging of AChE. This result along with reports on radiolabeled N-benzylpiperidine lactam benzisoxazole (IC(50) < 1 nM) and other radiolabeled benzylpiperidine derivatives (IC(50) > 1 nM) suggested that a subnanomolar IC(50) may not be the only important factor in determining the suitability of a radioligand for in vivo studies of AChE.

Acetylcholinesterase↗

In vitro metabolism studies of (18)F-labeled 1-phenylpiperazine using mouse liver S9 fraction.

The in vitro metabolism of 1-(4-[(18)F]fluoromethylbenzyl)-4-phenylpiperazine ([(18)F]1) and 1-(4-[(18)F]fluorobenzyl)-4-phenylpiperazine ([(18)F]2) was investigated using mouse liver S9 fraction. Results were compared to those of in vivo metabolism using mouse blood and bone and to in vitro metabolism using mouse liver microsomes. Defluorination was the main metabolic pathway for [(18)F]1 in vitro and in vivo. Based on TLC, HPLC and LC-MS data, [(18)F]fluoride ion and less polar radioactive metabolites derived from aromatic ring oxidation were detected in vitro, and the latter metabolites were rapidly converted into the former with time, whereas only the [(18)F]fluoride ion was detected in vivo. Similarly, the in vitro metabolism of [(18)F]2 using either S9 fraction or microsomes showed the same pattern as the in vivo method using blood; however, the radioactive metabolites derived from aromatic ring oxidation were not detected in vivo. These results demonstrate that liver S9 fraction can be widely used to investigate the intermediate radioactive metabolites and to predict the in vivo metabolism of radiotracers.

Animals↗

Synthesis and evaluation of 4-[(18)F]fluorothalidomide for the in vivo studies of angiogenesis.

In this study, we prepared 2-(2,6-dioxopiperidin-3-yl)-4-[(18)F]fluoroisoindole-1,3-dione (4-[(18)F]fluorothalidomide; [(18)F]1) for the in vivo studies of angiogenesis. Radiochemical synthesis of [(18)F]1 was carried out by labeling 4-trimethylammoniumthalidomide trifluoromethanesulfonate with nBu(4)N[(18)F]F in dimethyl sulfoxide (DMSO), followed by reverse-phase HPLC purification. Decay-corrected radiochemical yield of [(18)F]1 was 50-60%, with an effective specific activity of 42-120 GBq/micromol (end of synthesis). Incubation of the radioligand with human umbilical vein endothelial cells (HUVEC-C; American Type Culture Collection) showed a time-dependent increase in the uptake of the radioligand, and the uptake was inhibited by 8-11% in the presence of 10 microM thalidomide, indicating nonspecific binding of the radioligand. Positron emission tomography (PET) images of mice implanted with tumors in their right flanks revealed a marked accumulation of radioactivity in the livers, kidneys and bladders of the mice, and brain uptake appeared at approximately 40 min after injection. However, no radioactivity uptake was detected in the implanted tumor. Thin-layer chromatography (TLC), HPLC and LC-MS analyses of mouse liver microsomal metabolites of [(18)F]1 and 1 with or without nicotinamide adenine dinucleotide phosphate (NADPH) clearly revealed that the radioligand did not go through metabolic activation but underwent nonenzymatic hydrolysis at physiological pH. Therefore, these results would appear to indicate that [(18)F]1 may not be suitable for the in vivo studies of angiogenesis at least in mice, although it was reported that thalidomide and/or its hydrolysis products may be responsible for its activity in humans.

Animals↗

Incidence and radio-uptake patterns of femoral head avascular osteonecrosis at 1 year after renal transplantation: a prospective study with planar bone scintigraphy.

OBJECTIVES: We prospectively investigated the incidence of femoral head avascular osteonecrosis (AVN) and radio-uptake patterns of femoral heads on bone scintigraphy at 1 year after renal transplantation. METHODS: A total of 237 subjects (473 femoral heads) were included. A bone scintigraphy was performed at 12 +/- 1.1 months after renal transplantation, and 17 hips were painful at the time of bone scintigraphy. We graded the radioactivity in each femoral head as normal (grade 0), mildly increased (grade I), and definitely increased (grade II). Typical photon defects in the upper lateral femoral heads were evaluated separately. AVN was confirmed with clinical follow-up of more than 1 year and MRI and/or plain radiography findings. RESULTS: Femoral head AVN was detected in 15 of the 237 patients and 23 of the 473 femoral heads. When grade I and II activities were used as positive criteria, bone scintigraphy had a sensitivity of 91.3% (100% with pain) and specificity of 74.0% (100% with pain) for AVN diagnosis. When only grade II activity was considered positive, the rates were 56.5% (80.0% with pain) and 99.5% (100% with pain), respectively. The presence of a typical photon defect had a low sensitivity of 47.8%, although the specificity was high (99.1%). CONCLUSIONS: The incidence of femoral head AVN was low among a prospective cohort of renal transplantation recipients at the time of 1 year after engraftment. Planar bone scintigraphy is sufficient to diagnose AVN in symptomatic patients at risk for femoral head AVN using grade I and II activities as positive criteria.

Adult↗

A modified OSEM algorithm for PET reconstruction using wavelet processing.

Ordered subset expectation-maximization (OSEM) method in positron emission tomography (PET) has been very popular recently. It is an iterative algorithm and provides images with superior noise characteristics compared to conventional filtered backprojection (FBP) algorithms. Due to the lack of smoothness in images in OSEM iterations, however, some type of inter-smoothing is required. For this purpose, the smoothing based on the convolution with the Gaussian kernel has been used in clinical PET practices. In this paper, we incorporated a robust wavelet de-noising method into OSEM iterations as an inter-smoothing tool. The proposed wavelet method is based on a hybrid use of the standard wavelet shrinkage and the robust wavelet shrinkage to have edge preserving and robust de-noising simultaneously. The performances of the proposed method were compared with those of the smoothing methods based on the convolution with Gaussian kernel using software phantoms, physical phantoms, and human PET studies. The results demonstrated that the proposed wavelet method provided better spatial resolution characteristic than the smoothing methods based on the Gaussian convolution, while having comparable performance in noise removal.

Algorithms↗

Unilateral renal angiodysplasia in a girl with hypertension.

We report a case of very unusual renal vascular anomaly: angiodysplasia. The patient suffered from acute pyelonephritis immediately after birth. Renal ultrasonography, performed at age 1 day, revealed an enlarged left kidney with heterogeneously increased echogenicity, which involuted rapidly in 3 months. At age 10 years, she presented with severe hypertension during a course of acute pyelonephritis. Peripheral plasma renin activity was high. Computed tomographic angiogram revealed a very small but functioning left kidney. A single, narrow, left renal artery did not have focal stenosis. Pathology examination revealed dysplastic arterioles at the subcapsular area. After left nephrectomy, the blood pressure and the plasma renin activity were normalized. In conclusion, this is an unusual case of renal angiodysplasia, which induced renin-dependent hypertension.

Angiodysplasia↗

A clinical and molecular genetic study of hypophosphatemic rickets in children.

X-linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets, hereditary hypophosphatemic rickets with hypercalciuria, and tumor-induced osteomalacia share clinical and biochemical features, and are collectively referred to as hypophosphatemic rickets (HR). Recently, the molecular bases of HR were elucidated. A review of medical records and mutational analyses of the PHEX and FGF23 genes were performed on 17 unrelated Korean children with HR. The male-to-female ratio was 3:14, and 5 patients were familial. Initial laboratory tests revealed typical features of HR. Seven different PHEX mutations were detected in 8 patients: 2 missense mutations, 2 nonsense mutations, and 3 short deletions. No functional FGF23 mutation was detected in any patient. Patients with the PHEX mutation tended to have more severe skeletal disease than those without. Of the patients with this mutation, no genotype-phenotype correlation and no gene dosage effect were noted. Treatment with vitamin D and phosphate resulted in only a partial growth improvement in most cases, and was frequently complicated by hypercalciuria, hypercalcemia, nephrocalcinosis, or hyperparathyroidism. Renal glycosuria was detected in six cases and was associated with more severe skeletal disease. We conclude that current HR treatment is not fully safe or effective, and that close monitoring of treatment effectiveness and for complications should be performed during long-term treatment. No genotype-phenotype correlation in XLH was detected in this study, but a large-scaled study on this topic is warranted. The large proportion of patients with a normal genetic study suggests the possibility of other causative gene(s).

Child, Preschool↗