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>

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>

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>

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>

Immunochemical and Biological Analysis of Allergenicity with Excretory-Secretory Products of <i>Anisakis simplex</i> Third Stage Larva

Kim, J.S.,Kim, K.H.,Cho, S.,Park, H.Y.,Cho, S.W.,Kim, Y.T.,Joo, K.H.,Lee, J.S. S. Karger AG 2005 International archives of allergy and immunology Vol.136 No.4

<P><I>Background:</I><I>Anisakis simplex</I> third stage larvae (L3) are parasites that frequently give rise to allergic responses. The larvae molt into fourth stage larvae (L4), and at each stage they produce L3-excretory-secretory products (L3-ESP) and L4-ESP, respectively, which are different in their main protein constituents. Although the allergenicity of L4-ESP has been investigated by several research groups, research on the allergenicity of L3-ESP has not been carried out by any researcher. In this investigation, the allergenicity and antigenicity of L3-ESP were investigated in comparison with L4-ESP, using rat sera. <I>Methods:</I> Rat sera were produced by L3 oral infection two times with a 9-week interval. Larvae ESP prepared by culture were concentrated and fractioned using lyophilizer and a centrifugal filter device, respectively. Immunochemical analysis was performed using both indirect ELISA and immunoblot. Biological allergenicity was analyzed by RBL-2H3 exocytosis. <I>Results:</I> With the indirect ELISA, the optical density (OD) value of the nonfractioned (NF)-L3ESP was only one third of that of the NF-L4ESP in both specific IgM and IgG. On measuring specific IgE, the OD of NF-L3ESP was less than one tenth of that of NF-L4ESP. In addition, neither antigen nor allergen was shown in NF-L3ESP, but it was shown in NF-L4ESP with immunoblot. However, the biological allergenicity of NF-L3ESP was comparable to that of NF-L4ESP. To demonstrate the presence of any allergen, L3-ESP was fractioned and found to carry twelve visualized allergen bands from 10 to 186 kDa by immunoblot. <I>Conclusions:</I> These results indicate that L3-ESP may include the important allergens necessary to induce the allergy by L3 oral infection, as compared to L4-ESP.</P><P>Copyright © 2005 S. Karger AG, Basel</P>

The Use of Collagen Content as Determined by Spectral Domain Polarization-Sensitive Optical Coherence Tomography to Assess Colon Anastomosis Healing in a Rat Model

Son, K.H.,Jeong, H.-W.,Jung, W.-W.,Kim, H.-S.,Lee, S.K.,Kim, K.T.,Ahn, C.B.,Park, K.Y.,Kim, B.-M.,Lee, S.H. S. Karger AG 2014 European surgical research Vol.52 No.1

<P>Abstract</P><P><B><I>Background/Purpose:</I></B> Many studies have been undertaken to prevent anastomosis leakage of the colon, and several methods have been used to assess anastomosis healing, such as measurement of bursting pressure or hydroxyproline (a marker of collagen) content at the anastomosis site. However, these methods are inappropriate for comparing anastomosis healing at two time points in the same animals. In the present study, we measured the collagen level by spectral domain polarization-sensitive optical coherence tomography (SD-PS-OCT) to assess anastomosis healing. <B><I>Methods:</I></B> Sprague-Dawley rats were divided into groups C (saline-administered controls; study group) and M [a 5-fluorouracil (5-FU)-administered experimental group]. Immediately after end-to-end anastomosis of the colon, SD-PS-OCT images of anastomoses were taken (baseline). Animals were administered saline or 5-FU for 7 days. On the 7th postoperative day, SD-PS-OCT images were acquired, a histopathologic exam was performed, and hydroxyproline levels as well as mRNA expressions of collagen-1 and collagen-3 were measured at the anastomosis site. <B><I>Results:</I></B> Fibroblast proliferation and inflammatory cell infiltration were greater in group C than in group M. The mRNA expressions of collagen-1 and collagen-3 were substantially higher in group C. Hydroxyproline levels were higher in group M than in group C. Though collagen levels measured by SD-PS-OCT at 7 days were elevated compared with baseline in group C, no such changes were observed for group M. <B><I>Conclusion:</I></B> Collagen levels at the colon anastomosis site, measured with SD-PS-OCT, were not increased at 7 days postoperatively versus baseline when 5-FU was injected, but were increased in saline-treated controls. The measurement of collagen content by SD-PS-OCT was found to provide a good means of assessing anastomosis healing, because it allows in situ assessment of collagen contents at baseline and during the postoperative period.</P><P>© 2014 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>

Association of Extracellular Cleavage of E-Cadherin Mediated by MMP-7 with HGF-Induced in vitro Invasion in Human Stomach Cancer Cells

Lee, K.H.,Choi, E.Y.,Hyun, M.S.,Jang, B.I.,Kim, T.N.,Kim, S.W.,Song, S.K.,Kim, J.H.,Kim, J.-R. S. Karger AG 2007 European surgical research Vol.39 No.4

<P><I>Background:</I> Proteolytic shedding of the ectodomain of a variety of transmembrane proteins, including cell-to-cell adhesion molecules, has been observed in solid cancers. We have investigated whether extracellular cleavage of E-cadherin mediated by matrix metalloproteinase-7 (MMP-7) is involved in hepatocyte growth factor (HGF) induced in vitro invasion in stomach cancer cells. <I>Methods:</I> The effects of HGF on the expression of E-cadherin/β-catenin and MMP-7 at both the protein and mRNA levels were assessed in stomach cancer cells, NUGC-3 and MKN-28, and in cells in which the expression of MMP-7 was downregulated by transfection with a MMP-7 short hairpin RNA plasmid. <I>Results:</I> Treatment with HGF increased the extracellular cleavage of E-cadherin and the release of MMP-7 and reduced the level of E-cadherin in a dose- and time-dependent manner. HGF treatment repressed the phosphorylation of β-catenin in a Triton-soluble fraction, but enhanced this phosphorylation in a Triton-insoluble fraction. The association of E-cadherin with β-catenin was decreased by HGF treatment in the Triton-soluble fraction. In addition, treatment of MMP-7 short hairpin RNA transfected NUGC-3 cells with HGF resulted in no extracellular cleavage of E-cadherin and also decreased the in vitro cell invasion. <I>Conclusions:</I> These results suggest that incubation with HGF mediated the release of MMP-7, resulting in extracellular cleavage of E-cadherin from stomach cancer cells. This might be a key mechanism in HGF-induced in vitro invasion and metastasis.</P><P>Copyright © 2007 S. Karger AG, Basel</P>

Allergenicity of Sigma and Delta Class Glutathione S-Transferases from the German Cockroach

Jeong, Kyoung Yong,Jeong, Kyoung-jin,Yi, Myung-hee,Lee, Haeseok,Hong, Chein-Soo,Yong, Tai-Soon S. Karger AG 2008 International archives of allergy and immunology Vol.148 No.1

<P><I>Background:</I> Cockroach glutathione S-transferases (GSTs) are known to elicit strong IgE responses. This study was undertaken to compare the IgE reactivity of German cockroach GSTs, Bla g 5 (σ class) and δ class GST (BgGSTD1). <I>Methods:</I> Full-length Bla g 5 and BgGSTD1 were cloned, and their recombinant proteins were expressed and purified. Their IgE reactivities and cross-reactivities were examined by ELISA using sera from cockroach-sensitized subjects. <I>Results:</I> A predominant variant of Bla g 5 cDNA has amino acid substitutions at positions 10 (C to F) and 42 (N to K). BgGSTD1 has substitutions at positions 27 (E to N) and 207 (K to R). Sera from cockroach-sensitized patients showed 20.5% IgE reactivity to Bla g 5 and 17.9% IgE reactivity to BgGSTD1. However, inhibition studies using 1 serum sample with the highest IgE reactivity showed limited cross-reactivity. <I>Conclusions:</I> IgE-binding frequency to the cockroach GSTs was low, but the titer of IgE reactivity was strong in some sera. The inclusion of different classes of GSTs could be helpful for the delicate diagnosis and immunotherapy of cockroach allergy.</P><P>Copyright © 2008 S. Karger AG, Basel</P>

Is Confrontation Naming Performance in Alzheimer’s Disease the Nominal Linguistic Retrogenesis of Normal Development?

Kim, HyangHee,Yoon, Ji Hye,Lee, Ji Eun,Baek, Eun Jin,Sohn, Young H.,Na, Duk L. S. Karger AG 2011 European neurology Vol.66 No.4

<P>Abstract</P><P>We investigated confrontation naming performance of patients with Alzheimer’s disease (AD) and normal children (NC) to see if the nature of naming performance of AD patients is the reversal of that in normal development. Sixty items of the Boston Naming Test were given to 78 AD patients (and 40 age- and education-matched normal elderly) and 1,080 NC (3- to 14-year-olds). The analyses revealed that, firstly, the naming abilities of the AD patients demonstrated an inverse relationship with those of the NC. Secondly, from the clinical point of view, AD patients tended to lose vocabulary acquired later first while maintaining those acquired in earlier stages of development. Based on the findings, we claimed that this phenomenon was ‘a nominal retrogenesis’ in which ‘retrogenesis’ is ‘the process by which degenerative mechanisms reverse the order of acquisition in normal development’ as defined by Reisberg and colleagues.</P><P>Copyright © 2011 S. Karger AG, Basel</P>