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1.  Prospective Factor Analysis of Alpha Blocker Monotherapy Failure in Benign Prostatic Hyperplasia 
Korean Journal of Urology  2010;51(7):488-491.
We aimed to determine the treatment of choice criteria for benign prostatic hyperplasia (BPH) by analyzing the factors causing alpha-adrenergic receptor blocker (α-blocker) monotherapy failure.
Materials and Methods
This retrospective study enrolled 129 patients with BPH who were prescribed an α-blocker. Patients were allocated to a transurethral resection of prostate (TURP) group (after having at least a 6-month duration of medication) and an α-blocker group. We compared the differences between the two groups for their initial prostate volume, serum prostate-specific antigen (PSA), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual urine volume (PVR).
Of the 129 patients, 54 were in the TURP group and 75 were in the α-blocker group. Statistically significant differences (p<0.05) between the two groups were found in the prostate volume (50.8 ml vs. 34.4 ml), PSA (6.8 ng/ml vs. 3.6 ng/ml), Qmax (6.84 ml/sec vs. 9.99 ml/sec), and IPSS (27.3 vs. 16.8). According to the multiple regression analysis, the significant factors in α-blocker monotherapy failure were the IPSS (p<0.001) and prostate volume (p=0.015). According to the receiver operating characteristic (ROC) curve-based prediction regarding surgical treatment, the best cutoff value for the prostate volume and IPSS were 35.65 ml (sensitivity 0.722, specificity 0.667) and 23.5 (sensitivity 0.852, specificity 0.840), respectively.
At the initial diagnosis of BPH, patients with a larger prostate volume and severe IPSS have a higher risk of α-blocker monotherapy failure. In this case, combined therapy with 5-alpha-reductase inhibitor (5-ARI) or surgical treatment may be useful.
PMCID: PMC2907499  PMID: 20664783
Adrenergic alpha-antagonists; Prostatic hyperplasia; Transurethral resection of prostate
2.  Multicenter, prospective, comparative cohort study evaluating the efficacy and safety of alfuzosin 10 mg with regard to blood pressure in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia with or without antihypertensive medications 
The objective of this study was to assess the efficacy and safety of alfuzosin 10 mg monotherapy or combined antihypertensive medication on blood pressure (BP) in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS) with or without antihypertensive medication.
This was a 3-month, multicenter, randomized, open-label study in 335 patients aged ≥45 years with a clinical diagnosis of BPH/LUTS by medical history and clinical examination, a total International Prostatic Symptom Score (IPSS) ≥8 points, a maximum flow rate >5 mL/sec and ≤15 mL/sec, and a voided volume ≥120 mL. Eligible subjects were randomized to receive alfuzosin 10 mg as monotherapy (group 1) or alfuzosin 10 mg + antihypertensive combination therapy (group 2). Based on baseline BP and hypertensive history with or without antihypertensive medications at first medical examination, group 1 was divided into two subgroups of normotensive and untreated hypertensive patients, and group 2 into two subgroups of controlled hypertensive and uncontrolled hypertensive patients. The primary study outcomes were change in IPSS, BP, and heart rate from baseline. Secondary outcomes were change in IPSS-quality of life score, maximum flow rate, average flow rate, voided volume, and post-voided volume.
The overall BP change was not significantly different between groups 1 and 2 (systolic BP, P=0.825; diastolic BP, P>0.999). In patients with uncontrolled or untreated hypertension, alfuzosin 10 mg alone or combined with antihypertensive therapy significantly decreased systolic and diastolic BP. The mean difference in total IPSS and IPSS-quality of life scores from baseline between groups 1 and 2 was 0.45 (95% CI: −1.26, 2.16) and 0.12 (95% CI: −0.21, 0.45), respectively (both P>0.05). Maximum flow rate, average flow rate, voided volume, and post-voided volume at endpoint were numerically, but not significantly, changed from baseline (all P>0.05).
This study shows that alfuzosin 10 mg is effective and well tolerated in patients with BPH/LUTS with or without antihypertensive medications. However, in patients with uncontrolled or untreated hypertension, alfuzosin 10 mg alone or in combination with antihypertensive medication appears to decrease systolic and diastolic BP, and these patients should be warned about a decrease in BP on initiation of therapy.
PMCID: PMC4303366  PMID: 25653511
alfuzosin; lower urinary tract symptoms; benign prostatic hyperplasia; antihypertensive medication; blood pressure
3.  Pathogen Associated Molecular Pattern (PAMP)-Triggered Immunity Is Compromised under C-Limited Growth 
Molecules and Cells  2014;38(1):40-50.
In the interaction between plants and pathogens, carbon (C) resources provide energy and C skeletons to maintain, among many functions, the plant immune system. However, variations in C availability on pathogen associated molecular pattern (PAMP) triggered immunity (PTI) have not been systematically examined. Here, three types of starch mutants with enhanced susceptibility to Pseudomonas syringae pv. tomato DC3000 hrcC were examined for PTI. In a dark period-dependent manner, the mutants showed compromised induction of a PTI marker, and callose accumulation in response to the bacterial PAMP flagellin, flg22. In combination with weakened PTI responses in wild type by inhibition of the TCA cycle, the experiments determined the necessity of C-derived energy in establishing PTI. Global gene expression analyses identified flg22 responsive genes displaying C supply-dependent patterns. Nutrient recycling-related genes were regulated similarly by C-limitation and flg22, indicating re-arrangements of expression programs to redirect resources that establish or strengthen PTI. Ethylene and NAC transcription factors appear to play roles in these processes. Under C-limitation, PTI appears compromised based on suppression of genes required for continued biosynthetic capacity and defenses through flg22. Our results provide a foundation for the intuitive perception of the interplay between plant nutrition status and pathogen defense.
PMCID: PMC4314131  PMID: 25387755
Arabidopsis; carbon; defense; energy; flg22; NAC; starch; PAMP; Pseudomonas; PTI
4.  Urologists' Perceptions and Practice Patterns in Peyronie's Disease: A Korean Nationwide Survey Including Patient Satisfaction 
Korean Journal of Urology  2014;55(1):57-63.
A nationwide survey was conducted of Korean urologists to illustrate physicians' perceptions and real practical patterns regarding Peyronie disease (PD).
Materials and Methods
A specially designed questionnaire exploring practice characteristics and attitudes regarding PD, as well as patient satisfaction with each treatment modality, was e-mailed to 2,421 randomly selected urologists.
Responses were received from 385 practicing urologists (15.9%) with a median time after certification as an urologist of 12 years. Regarding the natural course, 87% of respondents believed that PD is a progressive disease, and 82% replied that spontaneous healing in PD occurred in fewer than 20% of patients. Regarding diagnosis of PD, the methods used were, in order, history taking with physical examination (98%), International Index of Erectile Function questionnaires (40%), intracavernous injection and stimulation (35%), and duplex sonography (28%). Vitamin E was most preferred as an initial medical management (80.2%), followed by phosphodiesterase-5 inhibitors (27.4%) and Potaba (aminobenzoate potassium, 20.1%). For urologists who administered intralesional injection, the injected agent was, in order, corticosteroid (72.2%), verapamil (45.1%), and interferon (3.2%). The most frequently performed surgical procedure was plication (84.1%), followed by excision and graft (42.9%) and penile prosthesis implantation (14.2%). Among the most popular treatments in each modality, the urologists' perceptions regarding the suitability of treatment and patient satisfaction were significantly different, favoring plication surgery.
The practice pattern of urologists depicted in this survey is in line with currently available Western guidelines, which indicates the need for development of further local guidelines based on solid clinical data.
PMCID: PMC3897632  PMID: 24466399
Data collection; Penile induration; Perception
5.  Constitutive Expression of Mammalian Nitric Oxide Synthase in Tobacco Plants Triggers Disease Resistance to Pathogens 
Molecules and Cells  2012;34(5):463-471.
Nitric oxide (NO) is known for its role in the activation of plant defense responses. To examine the involvement and mode of action of NO in plant defense responses, we introduced calmodulin-dependent mammalian neuronal nitric oxide synthase (nNOS), which controls the CaMV35S promoter, into wild-type and NahG tobacco plants. Constitutive expression of nNOS led to NO production and triggered spontaneous induction of leaf lesions. Transgenic plants accumulated high amounts of H2O2, with catalase activity lower than that in the wild type. nNOS transgenic plants contained high levels of salicylic acid (SA), and they induced an array of SA-, jasmonic acid (JA)-, and/or ethylene (ET)-related genes. Consequently, NahG co-expression blocked the induction of systemic acquired resistance (SAR)-associated genes in transgenic plants, implying SA is involved in NO-mediated induction of SAR genes. The transgenic plants exhibited enhanced resistance to a spectrum of pathogens, including bacteria, fungi, and viruses. Our results suggest a highly ranked regulatory role for NO in SA-, JA-, and/or ET-dependent pathways that lead to disease resistance.
PMCID: PMC3887790  PMID: 23124383
nitric oxide (NO); nitric oxide synthase (NOS); plant defense signaling; reactive oxygen species; salicylic acid
6.  Identification and Molecular Properties of SUMO-Binding Proteins in Arabidopsis 
Molecules and Cells  2011;32(2):143-151.
Reversible conjugation of the small ubiquitin modifier (SUMO) peptide to proteins (SUMOylation) plays important roles in cellular processes in animals and yeasts. However, little is known about plant SUMO targets. To identify SUMO substrates in Arabidopsis and to probe for biological functions of SUMO proteins, we constructed 6xHis-3xFLAG fused AtSUMO1 (HFAtSUMO1) controlled by the CaMV35S promoter for transformation into Arabidopsis Col-0. After heat treatment, an increased sumoylation pattern was detected in the transgenic plants. SUMO1-modified proteins were selected after two-dimensional gel electrophoresis (2-DE) image analysis and identified using matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We identified 27 proteins involved in a variety of processes such as nucleic acid metabolism, signaling, metabolism, and including proteins of unknown functions. Binding and sumoylation patterns were confirmed independently. Surprisingly, MCM3 (At5G46280), a DNA replication licensing factor, only interacted with and became sumoylated by AtSUMO1, but not by SUMO1ΔGG or AtSUMO3. The results suggest specific interactions between sumoylation targets and particular sumoylation enzymes.
PMCID: PMC3887670  PMID: 21607647
Arabidopsis; mass spectrometry; proteomics; SUMO binding proteins; Sumoylation
7.  A NAC transcription factor and SNI1 cooperatively suppress basal pathogen resistance in Arabidopsis thaliana 
Nucleic Acids Research  2012;40(18):9182-9192.
Transcriptional repression of pathogen defense-related genes is essential for plant growth and development. Several proteins are known to be involved in the transcriptional regulation of plant defense responses. However, mechanisms by which expression of defense-related genes are regulated by repressor proteins are poorly characterized. Here, we describe the in planta function of CBNAC, a calmodulin-regulated NAC transcriptional repressor in Arabidopsis. A T-DNA insertional mutant (cbnac1) displayed enhanced resistance to a virulent strain of the bacterial pathogen Pseudomonas syringae DC3000 (PstDC3000), whereas resistance was reduced in transgenic CBNAC overexpression lines. The observed changes in disease resistance were correlated with alterations in pathogenesis-related protein 1 (PR1) gene expression. CBNAC bound directly to the PR1 promoter. SNI1 (suppressor of nonexpressor of PR genes1, inducible 1) was identified as a CBNAC-binding protein. Basal resistance to PstDC3000 and derepression of PR1 expression was greater in the cbnac1 sni1 double mutant than in either cbnac1 or sni1 mutants. SNI1 enhanced binding of CBNAC to its cognate PR1 promoter element. CBNAC and SNI1 are hypothesized to work as repressor proteins in the cooperative suppression of plant basal defense.
PMCID: PMC3467076  PMID: 22826500
8.  Correlation between Metabolic Syndrome and Lower Urinary Tract Symptoms of Males and Females in the Aspect of Gender-Specific Medicine: A Single Institutional Study 
Korean Journal of Urology  2010;51(9):631-635.
We attempted to examine the correlation between metabolic syndrome and lower urinary tract symptoms (LUTS) in the aspect of gender-specific medicine.
Materials and Methods
A total of 922 patients participating in a health examination completed the International Prostate Symptom Score (IPSS) questionnaire and the Overactive Bladder Questionnaire Short Form (OABq-SF) symptom bother scale from March 2008 to July 2009. Metabolic syndrome was defined by using the National Cholesterol Education Program Adult Treatment Panel III criteria announced in 2001. We analyzed differences in lower urinary tract symptoms according to the presence of metabolic syndrome and the component elements of metabolic syndrome.
The subjects were 538 males and 384 females with a mean age of 48.8±6.8 years. Among all patients, the number of patients with metabolic syndrome was 143 (15.5%); there were 110 males (20.4%) and 33 females (8.6%), showing a significant difference. There were no differences in scores on the IPSS or OABq-SF with respect to the presence or absence of metabolic syndrome in males. In females, however, there were significant differences in the IPSS and OABq-SF depending on the presence or absence of metabolic syndrome. In males and females, the IPSS total score was significantly correlated with age. Also, high-density lipoprotein (HDL) cholesterol in males and triglyceride in females was significantly correlated with the IPSS total score.
There are sex differences in the morbidity rate of metabolic syndrome and its effect on lower urinary tract symptoms. Therefore, it is necessary to consider gender-specific medicine in the diagnosis and treatment of LUTS.
PMCID: PMC2941812  PMID: 20856648
Gender identity; Metabolic syndrome X; Urologic diseases
9.  Calcium and Calmodulin-Mediated Regulation of Gene Expression in Plants 
Molecular Plant  2009;2(1):13-21.
Sessile plants have developed a very delicate system to sense diverse kinds of endogenous developmental cues and exogenous environmental stimuli by using a simple Ca2+ ion. Calmodulin (CaM) is the predominant Ca2+ sensor and plays a crucial role in decoding the Ca2+ signatures into proper cellular responses in various cellular compartments in eukaryotes. A growing body of evidence points to the importance of Ca2+ and CaM in the regulation of the transcriptional process during plant responses to endogenous and exogenous stimuli. Here, we review recent progress in the identification of transcriptional regulators modulated by Ca2+ and CaM and in the assessment of their functional significance during plant signal transduction in response to biotic and abiotic stresses and developmental cues.
PMCID: PMC2639735  PMID: 19529824
Abiotic/environmental stress; calcium signaling/transport; gene expression
10.  Pathogen-induced binding of the soybean zinc finger homeodomain proteins GmZF-HD1 and GmZF-HD2 to two repeats of ATTA homeodomain binding site in the calmodulin isoform 4 (GmCaM4) promoter 
Nucleic Acids Research  2007;35(11):3612-3623.
Calmodulin (CaM) is involved in defense responses in plants. In soybean (Glycine max), transcription of calmodulin isoform 4 (GmCaM4) is rapidly induced within 30 min after pathogen stimulation, but regulation of the GmCaM4 gene in response to pathogen is poorly understood. Here, we used the yeast one-hybrid system to isolate two cDNA clones encoding proteins that bind to a 30-nt A/T-rich sequence in the GmCaM4 promoter, a region that contains two repeats of a conserved homeodomain binding site, ATTA. The two proteins, GmZF-HD1 and GmZF-HD2, belong to the zinc finger homeodomain (ZF-HD) transcription factor family. Domain deletion analysis showed that a homeodomain motif can bind to the 30-nt GmCaM4 promoter sequence, whereas the two zinc finger domains cannot. Critically, the formation of super-shifted complexes by an anti-GmZF-HD1 antibody incubated with nuclear extracts from pathogen-treated cells suggests that the interaction between GmZF-HD1 and two homeodomain binding site repeats is regulated by pathogen stimulation. Finally, a transient expression assay with Arabidopsis protoplasts confirmed that GmZF-HD1 can activate the expression of GmCaM4 by specifically interacting with the two repeats. These results suggest that the GmZF-HD1 and –2 proteins function as ZF-HD transcription factors to activate GmCaM4 gene expression in response to pathogen.
PMCID: PMC1920248  PMID: 17485478

Results 1-10 (10)