Effect of the Apolipoprotein E ε4 Allele on the Efficacy and Tolerability of Galantamine in the Treatment of Alzheimer’s Disease

Suh, Guk-Hee,Jung, Hee Yeon,Lee, Chang Uk,Oh, Byoung Hoon,Lee, Sang-Kyu,Lee, NamJin,Kim, JaeHyun,Kee, Baik Seok,Ko, Daekwan,Kim, Young-Hoon,Ju, Young-Su,Hong, InJa,Choi, Sungku S. Karger AG 2005 DEMENTIA AND GERIATRIC COGNITIVE DISORDERS Vol.21 No.1

<P><I>Objective:</I> To investigate the effect of the apolipoprotein E (ApoE) ε4 allele on the efficacy and tolerability of galantamine treatment. <I>Methods:</I> A total of 202 patients with mild to moderate Alzheimer’s disease participated in a 16-week, prospective, multi-center, randomized, double-blind galantamine trial in a Korean population. Patients were assessed at baseline and after 4, 8 and 16 weeks of randomized treatment using the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog/11), the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia Scale (DAD), the Behavioural Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) and adverse events. ApoE genotypes were determined for all subjects. <I>Results:</I> Of the 202 subjects, 115 carried at least one ApoE ε4 allele and 87 did not. In both ApoE ε4 carriers and ApoE ε4 noncarriers, significant improvements were detected relative to baseline on ADAS-cog/11, CIBIC-plus, DAD and BEHAVE-AD. ApoE ε4 noncarriers showed better improvement in mean total BEHAVE-AD score and mean psychosis (delusions and hallucinations) subscale score than ApoE ε4 carriers. The incidence of weight loss was significantly higher in ApoE ε4 carriers (n = 11; 9.6%) than in ApoE ε4 noncarriers (n = 1; 1.2%) during this 16-week study, even though 92% of patients who complained of weight loss completed this 16-week trial successfully. <I>Conclusion:</I> ApoE ε4 genotype does not affect galantamine-related improvements in cognition, global rating, function and behavior. Longer prospective studies with larger patient populations are required to confirm these new findings.</P><P>Copyright © 2006 S. Karger AG, Basel</P>

Early Diagnosis of Alzheimer's Disease and Parkinson's Disease Associated with Dementia Using Cerebral Perfusion SPECT

Song, In-Uk,Chung, Yong-An,Chung, Sung-Woo,Jeong, Jaeseung S. Karger AG 2014 Dementia and geriatric cognitive disorders Vol.37 No.5

<P>Abstract</P><P><B><I>Background:</I></B> Since patterns of cognitive dysfunction in mild Parkinson's disease associated with dementia (PDD) are similar to those in mild Alzheimer's disease (AD), it is difficult to accurately differentiate between these two types of dementia in their early phases using neuropsychological tests. The purpose of the current study was to investigate differences in cerebral perfusion patterns of patients with AD and PDD at the earliest stages using single photon emission computed tomography (SPECT). <B><I>Methods:</I></B> We consecutively recruited 31 patients with mild PDD, 32 patients with mild probable AD and 33 age-matched healthy subjects. All subjects underwent <SUP>99m</SUP>Tc-hexamethylpropyleneamine oxime perfusion SPECT and completed general neuropsychological tests. <B><I>Results:</I></B> We found that both mild PDD and AD patients showed distinct hypoperfusion in frontal, parietal and temporal regions, compared with healthy subjects. More importantly, hypoperfusion in occipital and cerebellar regions was observed only in mild PDD. <B><I>Conclusion:</I></B> The observation of a significant decrease in cerebral perfusion in occipital and cerebellar regions in patients with mild PDD is likely useful to differentiate between PDD and AD at the earliest stages.</P><P>© 2013 S. Karger AG, Basel</P>

Effects of Specific Genes Activating RAGE on Polycystic Kidney Disease

Park, Eun Young,Seo, Min Ji,Park, Jong Hoon S. Karger AG 2010 American journal of nephrology Vol.32 No.2

<P><I>Background:</I> Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and secretion of fluid and is associated with interstitial inflammation and fibrosis, resulting in the loss of renal function. We previously generated mice overexpressing <I>PKD2</I>, causing progressive cyst development with an inflammatory and fibrotic phenotype in the kidneys. <I>Methods:</I> To profile the gene expression related to inflammation and cystogenesis, microarray analysis was performed with kidney tissue from 6-, 12- and 18-month-old mice. Subsequently, levels and related mechanisms of selected genes, s100a8 and s100a9, were evaluated. <I>Results:</I> S100a8 and s100a9 was upregulated more than 2-fold and differently expressed in the cystic region. Receptor of advanced glycation end product (RAGE) is a putative cell surface receptor for s100a8/a9. It was expressed in cyst-lining cells and up-regulated pro-inflammatory transcription factor NF-κB in transgenic mice. We also confirmed RAGE expression in ADPKD patient kidneys. It was suggested that the signaling related to proliferative cystogenesis through previous reports; therefore, we confirmed that phosphorylated-ERK and cyst formation was reduced by treatment of RAGE-siRNA. <I>Conclusions:</I> The results may provide important information for the expression of s100a8/a9 and RAGE, linking progressive cystogenesis with inflammation in cystic kidney.</P><P>Copyright © 2010 S. Karger AG, Basel</P>

Association between the Self-Perception Period of Lower Urinary Tract Symptoms and the International Prostate Symptom Score

Shim, Sung Ryul,Kim, Jae Heon,Kim, Khae Hawn,Yoon, Sang Jin,Lee, Won Jin,Kim, Hae Joon,Bae, Jae Hyun S. Karger AG 2012 UROLOGIA INTERNATIONALIS Vol.88 No.4

<P>Abstract</P><P><B><I>Objectives:</I></B> The timing of visiting a hospital after self-perception of lower urinary tract symptoms (LUTS) is different between individuals. The association between the self-perception period (S-PP) of LUTS and the progression of LUTS has seldom been documented. The aim of this study was to investigate the association between the S-PP of LUTS and the International Prostate Symptom Score (IPSS). <B><I>Subjects and Methods:</I></B> This was a cross-sectional study comprising 267 men aged 40 years and older who participated in a prostate examination survey between February and May 2009. Survey questionnaires included items on the IPSS, the S-PPs of seven individual LUTSs assessed in the IPSS. <B><I>Results:</I></B> The S-PP of LUTS became significantly longer as the severity of LUTS increased. Of the seven symptoms, a weak urinary stream and nocturia showed longer S-PPs than others. Partial correlation between the S-PP and IPSS showed a statistically significant positive correlation. Linear regression analysis showed a statistically significant relationship that unstandardized coefficients included 0.051 and 0.005 for IPSS and quality of life. <B><I>Conclusions:</I></B> These findings suggest that the S-PP is an independent risk factor for LUTS progression. S-PPs have to be considered for treatment or prevention of LUTS.</P><P>Copyright © 2012 S. Karger AG, Basel</P>

Predictive Implications of Recurrent Transient Ischemic Attacks in Large-Artery Atherosclerosis

Kim, Seo Hyun,Han, Sang Won,Heo, Ji Hoe S KARGER AG 2006 Cerebrovascular Diseases Vol.22 No.4

<P><I>Background:</I> It is uncertain whether recurrent transient ischemic attacks (R-TIAs), when comparing with single TIAs (S-TIAs), have any distinct mechanisms. <I>Methods:</I> All consecutive patients with TIAs, who had been admitted for a 2-year period, were divided into two groups: those who had R-TIAs and those who had S-TIAs. Registry data, medical records, and imaging findings were reviewed and compared between the two groups. <I>Results:</I> There were 85 patients who had TIAs: 42 patients had R-TIAs, and 43 patients had S-TIAs. On univariate analysis, R-TIA patients had less cardiac embolic TIA sources, less weakness, less speech disturbances, shorter symptom duration, a longer time interval from onset to treatment, less abnormalities on diffusion-weighted magnetic resonance imaging, and more significant relevant arterial stenoses. After logistic regression analysis, independent factors associated with R-TIAs were symptom duration <10 min (odds ratio OR 3.62; 95% confidence interval CI 1.37-9.57), ≥50% stenosis of the clinically relevant artery (OR 7.08; 95% CI 1.29-38.71), and absence of cardiac embolic sources (OR 0.04; 95% CI 0.002-0.71). <I>Conclusions:</I> R-TIAs may have pathophysiological mechanisms distinct from those of S-TIAs and so may provide a clue for the etiologic diagnosis, in that patients with R-TIAs are more likely to have large-artery atherosclerosis.</P><P>Copyright © 2006 S. Karger AG, Basel</P>

Differentiating between Aphasic and Nonaphasic Stroke Patients Using Semantic Verbal Fluency Measures with Administration Time of 30 Seconds

Kim, HyangHee,Kim, JungWan,Kim, Deog Young,Heo, JiHoe S. Karger AG 2011 European neurology Vol.65 No.2

<P>Administration time of 1 min for semantic verbal fluency measures can be overly long and therefore bothersome for aphasic patients because they can often retrieve only a few items after a certain period of time. The purpose of this study was to determine whether an administration time of 30 s would be more efficient in differentiating among aphasics, nonaphasic stroke patients, and normal controls. The subjects were 53 stroke patients and 28 normal controls. They had to generate as many animal names as they could within a given time. The number of animal names is gradually diminished in three groups (p < 0.001) in each time frame, that is, during the entire 60 s, the initial 30 s, and the following 30 s. The reaction time (RT) measure indicated that the RT of the aphasic patients was significantly increased compared to those of the other two groups (p < 0.001). The most optimal cutoff scores that differentiated each group are presented. These results suggest that an administration time of 30 s has discriminative validity to differentiate between the two patient groups. This shorter administration time could make the test more efficient by reducing the burden on both examiners and aphasic patients.</P><P>Copyright © 2011 S. Karger AG, Basel</P>

Activation of T-Cell-Factor-Dependent Transcription by Kaposi’s Sarcoma-Associated Herpesvirus Replication Transactivation Activator

Cha, Seho,Yoon, Hee Jung,Kim, Su-Jung,Seo, Taegun S. Karger AG 2011 Intervirology Vol.54 No.2

<abstitle>Abstract</abstitle><P><I>Objective:</I> To elucidate the cellular function of Kaposi’s sarcoma-associated herpesvirus (KSHV) replication transactivation activator (RTA) at the transcriptional level. <I>Methods:</I> Transcriptional activation of T-cell-factor (TCF)-dependent genes by RTA was determined using the luciferase reporter assay. The specific regions of RTA required for the activation of TCF-dependent transcription and association with β-catenin were established. <I>Results:</I> RTA specifically activated TCF-dependent transcription in a dose-dependent manner, to an extent comparable to the activation achieved by latency-associated nuclear antigen. In contrast, other KSHV viral proteins investigated, such as basic leucine zipper and viral interferon regulatory factor 1, did not affect TCF-dependent transcription. The C-terminal region of RTA appeared to be necessary for transcription. However, RTA did not affect the β-catenin level or the subcellular localization thereof. <I>Conclusion:</I> Our results collectively demonstrate that KSHV RTA activates TCF-dependent transcription without involving the β-catenin pathway.</P><P>Copyright © 2010 S. Karger AG, Basel</P>

Prognostic Significance of Pretreatment ¹⁸F-FDG PET/CT in Patients with Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma Treated by Radioimmunotherapy Using ¹³¹I-Rituximab

Lim, Ilhan,Park, Joon Yeun,Kang, Hye Jin,Hwang, Jae Pil,Lee, Seung Sook,Kim, Kyeong Min,Choi, Tae Hyun,Yang, Sung Hyun,Kim, Byung Il,Choi, Chang Woon,Lim, Sang Moo S. Karger AG 2013 Acta haematologica Vol.130 No.2

<P>Abstract</P><P><B><I>Aims:</I></B> It was the aim of this paper to identify prognostic factors in patients with relapsed or refractory B-cell non-Hodgkin's lymphomas, treated by radioimmunotherapy (RIT) with radioiodinated human/murine chimeric anti-CD20 monoclonal antibody rituximab (<SUP>131</SUP>I-rituximab). <B><I>Methods:</I></B> Twenty-four patients were enrolled prospectively and were treated with unlabeled rituximab 70 mg and a therapeutic activity (median 7.3 GBq) of <SUP>131</SUP>I-rituximab. Contrast-enhanced <SUP>18</SUP>F-FDG PET/CT scans were performed before and after 1 month of RIT. Tumor sizes and maximum standardized uptake values (SUV<SUB>max</SUB>) of scans were measured. <B><I>Results:</I></B> Four of the 24 patients survived. High SUV<SUB>max</SUB> in a pretreatment scan was found to be related to poorer overall survival (OS) and progression-free survival (p = 0.04 and 0.02, respectively). Furthermore, a large tumor size in a pretreatment scan was associated with poorer OS but not with progression-free survival (p < 0.01 and p = 0.07, respectively). By multivariate analyses, a high SUV<SUB>max</SUB>, a large tumor size in a pretreatment scan and diffuse large B-cell lymphoma histology were significantly associated with poorer OS [p = 0.04/hazard ratio (HR) = 3.54, p < 0.01/HR = 5.52, and p = 0.02/HR = 3.38, respectively). <B><I>Conclusion: </I></B>SUV<SUB>max</SUB> and tumor size determined by a pretreatment <SUP>18</SUP>F-FDG PET/CT result as significant predictors of OS in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma treated by RIT.</P><P>Copyright © 2013 S. Karger AG, Basel</P>

<i>Coriandrum sativum</i> L. Protects Human Keratinocytes from Oxidative Stress by Regulating Oxidative Defense Systems

Park, G.,Kim, H.G.,Kim, Y.O.,Park, S.H.,Kim, S.Y.,Oh, M.S. S. Karger AG 2012 Skin pharmacology and physiology Vol.25 No.2

<P><I>Background:</I> Oxidative radicals are major environmental causes of human skin damage. Oxidative defense factors, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2), are centrally involved in repairing skin cells or protecting them from oxidative damage. <I>Coriandrum sativum</I> L. (coriander; CS) is a commonly consumed food and a traditional phytomedicine in Asia and Europe. In this study, we examined the protective effects of a standardized CS leaf extract against oxidative stress in human HaCaT keratinocytes. <I>Methods and Results:</I> CS significantly and dose-dependently protected cells against reduced cell viability caused by H<SUB>2</SUB>O<SUB>2</SUB>-induced damage, as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Other assays demonstrated that CS protected HaCaT cells by increasing the levels of glutathione and activities of oxidative defense enzymes, such as superoxide dismutase and catalase. Moreover, it increased the expression of activated Nrf2, which plays a crucial role in protecting skin cells against oxidative stress. <I>Conclusion:</I> These results suggest that CS protects human keratinocytes from H<SUB>2</SUB>O<SUB>2</SUB>-induced oxidative stress through antioxidant effects.</P><P>Copyright © 2012 S. Karger AG, Basel</P>

Survival of Alzheimer's Disease Patients in Korea

Go, Seok Min,Lee, Kang Soo,Seo, Sang Won,Chin, Juhee,Kang, Sue J.,Moon, So Young,Na, Duk L.,Cheong, Hae-Kwan S. Karger AG 2013 Dementia and geriatric cognitive disorders Vol.35 No.3

<P>Abstract</P><P><B><I>Background/Aims:</I></B> The natural history of Alzheimer's disease (AD) has rarely been studied in the Korean population. Our study on survival analyses in Korean AD patients potentially provides a basis for cross-cultural comparisons. <B><I>Methods:</I></B> We studied 724 consecutive patients from a memory disorder clinic in a tertiary hospital in Seoul, who were diagnosed as having AD between April 1995 and December 2005. Deaths were identified by the Statistics Korea database. The Kaplan-Meier method was used for survival analysis, and a Cox proportional hazard model was used to assess factors related to patient survival. <B><I>Results:</I></B> The overall median survival from the onset of first symptoms and from the time of diagnosis was 12.6 years (95% confidence interval 11.7-13.4) and 9.3 years (95% confidence interval 8.7-9.9), respectively. The age of onset, male gender, history of diabetes mellitus, lower Mini-Mental State Examination score, and higher Clinical Dementia Rating score were negatively associated with survival. There was a reversal of risk of AD between early-onset and later-onset AD, 9.1 years after onset. <B><I>Conclusions:</I></B> The results of our study show a different pattern of survival compared to those studies carried out with western AD populations. Mortality risk of early-onset AD varied depending on the duration of follow-up.</P><P>Copyright © 2013 S. Karger AG, Basel</P>