Magnetic resonance imaging of amyloid plaques using hollow manganese oxide nanoparticles conjugated with antibody a&bgr;1–40 in a transgenic mouse model

Kim, Jae-Hun,Ha, Tae Lin,Im, Geun Ho,Yang, Jehoon,Seo, Sang Won,Lee, In Su,Lee, Jung Hee Lippincott Williams Wilkins, Inc. 2013 NEUROREPORT - Vol.24 No.1

<P>In this study, we have shown the feasibility of hollow manganese oxide nanoparticles (HMON) conjugated with an antibody of A beta 1-40 peptide (abA beta 40) (HMON-abA beta 40) for MRI of amyloid plaques in APP/PS1 transgenic mice. MR brain images in APP/PS1 transgenic mice and their nontransgenic littermates were acquired using a 7.0 T MRI system before, and 24 and 72 h after an injection of HMON-abA beta 40. After the injection of HMON-abA beta 40, we found hyperenhanced spots in the frontal cortex area on T1-weighted MR images for transgenic mice, which corresponded qualitatively to amyloid plaques detected by thioflavin-S staining. For quantitative analysis, percent MR signal changes in six brain regions (olfactory cortex, frontal cortex, cerebral cortex, thalamus, hippocampus, and cerebellar cortex) were compared between transgenic and wild-type mice. We found significant increases in the percent MR signal changes in the olfactory cortex, frontal cortex, cerebral cortex, and hippocampus, but there were no significant differences in the thalamus and cerebellar cortex for transgenic mice compared with wild-type mice. This unique strategy allowed us to detect brain regions subjected to amyloid plaque deposition in Alzheimer's disease transgenic mouse models and has a potential to be developed for human applications, which has a current utility in preclinical research, particularly in monitoring therapeutic response for drug development in Alzheimer's disease. NeuroReport 24:16-21 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. NeuroReport 2013, 24:16-21</P>

Hypervascular Focus in the Nonhypervascular Nodule ('Nodule-in-Nodule') on Dynamic Computed Tomography: Imaging Evidence of Aggressive Progression in Hepatocellular Carcinoma

Yu, Jeong-Sik,Chung, Jae-Joon,Kim, Joo Hee,Kim, Ki Whang Lippincott Williams Wilkins, Inc. 2009 Journal of computer assisted tomography Vol.33 No.1

OBJECTIVE:: The purpose of this study was to investigate the early manifestation of hypervascular hepatocellular carcinomas by means of evaluating the 'nodule-in-nodule' hepatic lesions depicted on dynamic computed tomography. METHODS:: For 26 lesions with hypervascular foci in nonhypervascular nodules in 23 patients with cirrhotic liver, the size of the lesions was measured during the initial and follow-up studies in patients who had a comparable follow-up computed tomography or magnetic resonance imaging studies (ranging from 46 to 399 days). RESULTS:: The mean volume doubling time of the total 26 inner nodules was 36 days, which was significantly shorter than the doubling time for the outer nodules (mean, 257 days for 18 enlarged lesions) (P < 0.001). CONCLUSIONS:: Because of the rapid progression of the inner hypervascular hepatocellular carcinomas, recognition of nodule-in-nodule lesions is essential for considering short-term follow-up or immediate treatment when managing patients with cirrhosis.

Metastasis Versus Focal Eosinophilic Infiltration of the Liver in Patients With Extrahepatic Abdominal Cancer: An Evaluation With Gadobenate Dimeglumine-Enhanced Magnetic Resonance Imaging

Park, Mi-Suk,Kim, Myeong-Jin,Lim, Joon Suk,Kim, Seung Hyung,Kim, Hua-Sun,Chung, Yong Eun,Kim, Ki Whang Lippincott Williams Wilkins, Inc. 2009 Journal of computer assisted tomography Vol.33 No.1

PURPOSE:: To determine the performance of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) to differentiate focal eosinophilic infiltration (FEI) from metastasis. MATERIALS AND METHODS:: Gadobenate dimeglumine-enhanced MRI conducted in 38 patients (lesions of 43 metastases and 33 FEIs) with extrahepatic abdominal carcinoma were reviewed retrospectively. Images were divided into 2 sets. Set 1 was composed of precontrast MRI with dynamic phase images. Set 2 included hepatobiliary phase images in addition to the images of set 1. Two blinded radiologists independently categorized each set of images into 5 grades to differentiate metastases from FEI. The area under the receiver operating characteristic curve (Az) was calculated for each set of images. The observers evaluated the shape, signal intensity (SI), and enhancement pattern of the lesions in consensus. RESULTS:: The Az values for set 2 images (reader 1: 0.976, and reader 2: 0.743) were greater than those of set 1 (0.961 and 0.709), without statistical significance (P = 0.470 and 0.223). Target appearance was seen in 27 of 43 (63%) metastases on hepatobiliary phase imaging, but none on the FEI. Twenty-five (76%) of the 33 FEIs showed intermingled hypo-SI and iso-SI on hepatobiliary phase images with changing size and shape compared to the T2-weighted images, whereas none of the metastases did. CONCLUSION:: Gadobenate dimeglumine-enhanced MRI may assist in the differentiation of FEI from metastasis by highlighting the distinctive features between them, even without hepatobiliary phase imaging.

Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging in Pyogenic and Tuberculous Spondylitis: Preliminary Study

Lee, In Sook,Lee, Jung Sub,Kim, Seong-Jang,Jun, Sungmin,Suh, Keun Tak Lippincott Williams Wilkins, Inc. 2009 Journal of computer assisted tomography Vol.33 No.4

OBJECTIVE:: The purpose of this study was to compare the effectiveness of positron emission tomography (PET)/computed tomography (CT) in distinguishing between tuberculous and pyogenic spondylitis with that of magnetic resonance imaging (MRI). METHODS:: Twenty-two consecutive patients confirmed to have tuberculous or pyogenic spondylitis were examined with both MRI and dual-time point PET/CT. The serum C-reactive protein (CRP) level was measured. The early and delayed PET/CT data were analyzed using the standardized uptake value (SUV). The radiologists scored the MRI findings and differentiated between tuberculous and pyogenic spondylitis. Each MRI result and CRP value was compared with the SUVs of PET/CT. RESULTS:: The reviewers identified tuberculous spondylitis (n = 11) on MRI, with a sensitivity, specificity, and positive predictive values of 90%, 100%, and 100%, respectively. For pyogenic spondylitis (n = 11), the corresponding values were 100%, 90%, and 92%, respectively. There was a significant difference in the maximum SUVs of the early phase between tuberculous and pyogenic spondylitis (P = 0.028). Magnetic resonance imaging was superior to PET/CT in differentiating between tuberculous and pyogenic spondylitis (P = 0.043). A comparison of the maximum SUVs of the early phase and CRP values revealed a correlation coefficient of 0.581 (P = 0.006). CONCLUSIONS:: The maximum SUVs of early-phase PET/CT may be complementary to MRI for differentiating pyogenic and tuberculous spondylitis and reflecting the activity of infectious spondylitis.

Prognosis of Paraquat-Induced Ocular Surface Injury: Therapeutic Effect of Amniotic Membrane Transplantation

Yoon, Kyung-Chul,Im, Seong-Kyu,Kim, Jae-Chan,Yoon, Kyoung-Won,Choi, Sung-Kyu Lippincott Williams Wilkins, Inc. 2009 Cornea Vol.28 No.5

PURPOSE:: To investigate the prognosis of paraquat-induced ocular surface injury and the therapeutic efficacy of amniotic membrane transplantation for the treatment of ocular surface damage. METHODS:: Twenty patients (26 eyes) with ocular surface injury caused by paraquat were studied. Twelve patients (14 eyes) underwent amniotic membrane transplantation combined with medical treatment (group A), and 8 patients (12 eyes) received medical treatment only (group B). Visual acuity, time to epithelial defect closure, stromal haze, and complications were analyzed. RESULTS:: The grade of the ocular surface injury was mild in 19 eyes (73.1%). Visual acuity improved in 20 eyes (76.9%). The epithelial defect healed completely in 25 eyes (96.2%), with a mean healing time of 16.04 ± 6.22 days. At the final visit, 80.8% of cases had no stromal haze. The mean time to epithelial defect closure was 13.43 ± 3.55 days in group A and 19.18 ± 7.25 days in group B (P = 0.03). Complications included punctal stenosis (2 eyes) and pannus (1 eye) in group A and conjunctivalization (1 eye) and symblepharon (1 eye) in group B. CONCLUSIONS:: Paraquat-induced ocular surface injury had a relatively good prognosis. Amniotic membrane transplantation was helpful in shortening the time to closure of the epithelial defect.

Association of IL-13 polymorphisms with leukotriene receptor antagonist drug responsiveness in Korean children with exercise-induced bronchoconstriction

Kang, Mi-Jin,Lee, So-Yeon,Kim, Hyo-Bin,Yu, Jinho,Kim, Byoung-Ju,Choi, Won-Ah,Jang, Seong-Ok,Hong, Soo-Jong Lippincott Williams Wilkins, Inc. 2008 PHARMACOGENETICS AND GENOMICS Vol.18 No.7

BACKGROUND: IL-13 is a pivotal cytokine in allergic inflammation and bronchial hyperresponsiveness, and is known to influence leukotriene levels. OBJECTIVE: We investigated whether IL-13 polymorphisms may be associated with clinical phenotypes and drug responsiveness to the leukotriene receptor antagonist (LTRA) in Korean asthmatic children with exercise-induced bronchoconstriction (EIB). METHODS: We enrolled 242 normal controls and 374 patients with asthma. Of the asthmatic patients, 100 performed exercise challenge tests before and after receiving montelukast (5 mg/day) for 8 weeks and included 80 subjects in drug responsiveness analysis. We assessed IL-13 polymorphisms (−1512A/C, −1112C/T, +2044G/A) through PCR–restriction fragment length polymorphism analysis. RESULTS: Significantly higher total IgE levels and maximum percent fall in forced expiratory volume in 1 s (FEV1) (%) after exercise challenge test were found in asthmatic patients carrying one or two copies of the IL-13 +2044A versus those homozygous for +2044G (P=0.011 and 0.040, respectively). We further noted a correlation of total IgE with maximum percent fall in FEV1 (%) in asthmatic patients, as well as a reverse correlation with improvement of maximum percent fall in FEV1 (%) after exercise challenge tests. Finally, we observed a significant association between responsiveness to montelukast and IL-13 −1112C/T polymorphism and the haplotype of IL-13 polymorphisms. CONCLUSION: The IL-13 +2044G/A polymorphism may be associated with atopy and EIB severity in Korean children with EIB, and thus could potentially be considered as a disease-modifying gene. Moreover, the IL-13 −1112C/T polymorphism and the haplotype of IL-13 polymorphisms seem to be associated with LTRA drug responsiveness, and thus might prove useful as a target for modulation of LTRA drug responsiveness.

Effect of CYP2C9 and VKORC1 genotypes on early-phase and steady-state warfarin dosing in Korean patients with mechanical heart valve replacement

Kim, Ho-Sook,Lee, Sang Seop,Oh, Minkyung,Jang, Yin-Jin,Kim, Eun-Young,Han, II Yong,Cho, Kwang-Hyun,Shin, Jae-Gook Lippincott Williams Wilkins, Inc. 2009 PHARMACOGENETICS AND GENOMICS Vol.19 No.2

OBJECTIVES: The effect of CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1) genotypes was evaluated for the early-phase and steady-state warfarin dosing in Korean patients with mechanical heart valve replacement. METHODS: The genotypes of CYP2C9 variants including CYP2C9*3, CYP2C9*13, and CYP2C9*14, and VKORC1 1173C>T were assessed for the association with warfarin dosing in 265 patients whose data were collected for warfarin dose; international normalized ratio (INR), comedication, comorbidity, and other clinical characteristics. RESULTS: In the early phase of warfarin therapy, the combined genotypes of CYP2C9 and VKORC1 caused statistically significant difference in warfarin dose from day 7 of warfarin dosing and the subsequent time course of dose increase showed significant difference among the three different genotypes (P<0.001). Compared with patients with CYP2C9 wild type, the patients with heterozygous CYP2C9 variants have delayed time to reach stable dose [adjusted hazard ratio (HRadj): 0.48; 95% confidence interval (CI): 0.27–0.85] and tended to have high risk for the first INR greater than 3.5 (HRadj: 1.64; 95% CI: 0.98–2.75). The patients with the VKORC1 CT genotype showed no significant difference in the time to reach stable dose but statistically significant low HR for time to first INR greater than 3.5 compared with those with VKORC1 TT genotype (HRadj: 0.25; 95% CI: 0.13–0.51). The observed warfarin maintenance dose was best explained by a model including covariates of age, weight, concurrent congestive heart failure/cardiomyopathy, INR-increasing drugs, aspirin, dietary supplements, and CYP2C9 and VKORC1 genotypes (R=0.56). CONCLUSION: The heterozygous CYP2C9 and VKORC1 genotypes influence warfarin dosing in an early phase as well as steady state of warfarin therapy in Korean patients with mechanical heart valve replacement.

Helicobacter pylori genotyping findings from multiple cultured isolates and mucosal biopsy specimens: strain diversities of Helicobacter pylori isolates in individual hosts

Kim, Young Sun,Kim, Nayoung,Kim, Jung Mogg,Kim, Mi Soon,Park, Ji Hyun,Lee, Mi Kyoung,Lee, Dong Ho,Kim, Joo Sung,Jung, Hyun Chae,Song, In Sung Lippincott Williams Wilkins, Inc. 2009 European journal of gastroenterology & hepatology Vol.21 No.5

OBJECTIVES: To determine whether the genotypes of virulent genes in Helicobacter pylori isolates and mucosal biopsy specimens differ in individuals, and to investigate whether different isolates from single hosts show strain differences. METHODS: Sixty-one Korean patients with H. pylori infection were enrolled. PCR and DNA sequencing for cagA, vacA, iceA, and oipA were performed using DNA extracted from H. pylori isolates cultured (2.6 H. pylori isolates per host) directly from antral mucosal biopsy specimens. Strain diversities were analyzed in 234 H. pylori isolates obtained from 43 hosts with at least two H. pylori isolates from antrum and body, respectively, and random amplified polymorphic DNA fingerprinting was carried out on isolates obtained from patients who showed genotype diversity. RESULTS: The patients with inconsistent genotyping results between H. pylori isolates and mucosal biopsies were as follows: 16.4% for cagA, 19.7% for vacA m, 47.5% for vacA s1, 6.6% for vacA i-region, 34.4% for iceA, and 21.3% for oipA. Genotyping of H. pylori isolates from same hosts showed diversity in 58.1% (25/43 patients). When random amplified polymorphic DNA -PCR fingerprinting was carried out on 104 H. pylori isolates from 19 patients who showed genotype diversity among their isolates, 68.4% (13 of 19 patients) of patients were found to be colonized by multiple H. pylori strains. CONCLUSION: This study shows that the genotypes of virulent genes from biopsy samples produced different results when compared with those obtained from H. pylori isolates, especially for vacA s1, and iceA. In addition, about 60% of our patients were infected by multiple H. pylori strains.

Differentiation of Benign and Malignant Solid Pseudopapillary Neoplasms of the Pancreas

Chung, Yong Eun,Kim, Myeong-Jin,Choi, Jin-Young,Lim, Joon Seok,Hong, Hye-Suk,Kim, Young Chul,Cho, Hyeon Je,Kim, Kyung Ah,Choi, Sun Young Lippincott Williams Wilkins, Inc. 2009 Journal of computer assisted tomography Vol.33 No.5

OBJECTIVE:: The aim of this study was to investigate differential imaging features between benign and malignant solid pseudopapillary neoplasms (SPN) of the pancreas on computed tomographic and magnetic resonance imagings. METHODS:: Between January 2001 and January 2007, we identified 30 patients with confirmed SPN by surgery. The computed tomographic and magnetic resonance images were reviewed by 3 radiologists in consensus. Each tumor was analyzed for the following categories: location of tumor, tumor margin, proportion of solid component, morphology of capsule, growth pattern, calcification, and presence of upstream pancreatic ductal dilatation. RESULTS:: Benign SPN usually had oval/round or smoothly lobulated margins, and malignant SPN more commonly had focal lobulated margins (P = 0.027). Presence of complete encapsulation was more frequently seen in benign SPN, whereas focal discontinuity of capsule was more commonly seen in malignant SPN (P = 0.005). There was no statistical difference between benign and malignant tumors in other imaging findings. CONCLUSIONS:: A focal lobulated margin and a focal discontinuity of the capsule may suggest malignant SPN, whereas a round or smoothly lobulated margin and a complete encapsulation were more commonly seen in benign SPN.

Changing prevalence of upper gastrointestinal disease in 28 893 Koreans from 1995 to 2005

Kim, Jin Il,Kim, Sang Gyun,Kim, Nayoung,Kim, Jae Gyu,Shin, Sung Jae,Kim, Sang Woo,Kim, Hyun Soo,Sung, Jae Kyu,Yang, Chang Heon,Shim, Ki-Nam,Park, Seun Ja,Park, Joon Yong,Baik, Gwang Ho,Lee, Sang Woo,P Lippincott Williams Wilkins, Inc. 2009 European journal of gastroenterology & hepatology Vol.21 No.7

OBJECTIVES: Changes in the pattern of gastrointestinal diseases in a population tend to be influenced by changes in diet and lifestyle. Shifts in gastrointestinal disease from 1995 to 2005 in Korea were evaluated, retrospectively. METHODS: Seventeen nationwide medical centers participated in this study. The cross-sectional review of endoscopic findings in 28 893 patients included 8441 patients from 1995, 10 350 patients from 2000, and 10 102 patients from 2005. RESULTS: The prevalence of reflux esophagitis increased from 1.8% in 1995 to 5.9% in 2000 and 9.1% in 2005 (P<0.001, the P value was only for the comparison between 1995 and 2005, the followings were as same). The prevalence of peptic ulcer diseases was 18.0% in 1995, 19.1% in 2000, and 20.2% in 2005 (P<0.001). Although no significant differences were noted in duodenal ulcers (8.4, 8.7, and 8.2%, P=0.449), gastric ulcers showed an increasing trend (9.6, 10.5, and 12.0%, P<0.001). The prevalence of gastric cancer increased from 3.4% in 1995 to 4.5% in 2000 (P<0.001), but then decreased to 2.4% in 2005 (P<0.001). The incidence of advanced gastric cancer was 2.5, 3.2, and 1.3%, respectively (P<0.001), and that of early gastric cancer remained constant with rates of 0.8%, 1.3, and 1.1%, respectively (P=0.056). CONCLUSION: The cross-sectional review of data collected in 1995, 2000, and 2005 showed an increase in reflux esophagitis and peptic ulcer diseases. Meanwhile, the prevalence of gastric cancer increased until 2000, but decreased in 2005.