Gilho Lee

The association between Toll-like receptor 4 (TLR4) polymorphisms and the risk of prostate cancer in Korean men

The Toll-like receptor 4 (TLR4) has a wide spectrum of bacteria recognition receptors that may be involved in the signaling of the immune responses in the prostate. A few association studies have assessed the relationship between the risk of prostate cancer (PC) and the polymorphism in the TLR4 gene in European-ancestry populations. To evaluate the association of TLR4 polymorphisms and the risk for PC in Korean men, we genotyped five single-nucleotide polymorphisms (SNPs) of the TRL4 gene (rs11536858, rs1927914, 1927911, rs11536891, and rs11536897) by PCR-restriction fragment length polymorphism from unrelated 157 PC patients and 143 age-matched controls. The rs1927911 SNP increased the risk of PC (adjusted odds ratio ORadj=2.73, 95% CI=1.54-4.87 for the TC genotype; ORadj=6.68, 95% CI=3.27-13.66 for the CC genotype). The GG genotype of the rs11536858 SNP also carried increased risk (ORadj=2.296, 95% CI=1.07-4.93). There was no statistically significant correlation between any of the SNPs of TRL4 and such PC prognostic factors as Gleason grade, initial prostate-specific antigen level, or tumor stage. In conclusion, inherited differences in the TLR4 gene influence the risk of PC in Korean men.

Risk factors for antimicrobial resistance among the Escherichia coli strains isolated from Korean patients with acute uncomplicated cystitis: a prospective and nationwide study.

We investigated the risk factors for resistance to ciprofloxacin, cefazolin, ampicillin and co-trimoxazole in Escherichia coli isolates from urine of Korean female patients with acute uncomplicated cystitis (AUC). A total of 225 patients and their E. coli isolates were prospectively and nationwidely enrolled between May and October, 2006. All the antimicrobials did not show any differences according to the age group. A higher rate of ciprofloxacin resistance was observed in the south (OR: 3.04, 95% CI: 1.19-7.80 for Chungcheong-do & Jeolla-do; OR: 3.04, 95% CI: 1.22-7.58 for Gyeongsang-do) compared to Gyeonggi-do. Two recurrences of AUC in the past year was an important risk factor for antimicrobial resistance (ciprofloxacin; OR: 6.71, 95% CI: 1.86-24.11 and cefazolin; OR: 5.72, 95% CI: 1.20-27.25). However, the resistance to co-trimoxazole and ampicillin was not associated with any of the risk factors. This study also revealed the pattern of multi-drugs resistance in ciprofloxacin resistant E. coli strains. In conclusion, for Korean patients with two more recurrences of AUC in the past year, it is strongly recommended to perform an antimicrobial sensitivity test with a urine sample before empirical treatment.

Ciprofloxacin Resistance in Enterococcus faecalis Strains Isolated From Male Patients With Complicated Urinary Tract Infection

Purpose Urinary tract infection (UTI) is one of the most prevalent bacterial infections, and fluoroquinolone therapy is a well-known standard regimen for UTI. The prevalence and risk factor analysis of fluoroquinolone resistance in enterococcal UTIs are not well documented. The aim of this study was to evaluate the antimicrobial susceptibility and risk factors for ciprofloxacin resistance in Enterococcus faecalis strains isolated from patients with complicated UTI. Materials and Methods We evaluated 81 E. faecalis strains isolated from 81 male patients at a single teaching hospital over 3 years. The Vitek 2 automatic system was used for antimicrobial susceptibility analysis. Results Antimicrobial resistance rates were rare for ampicillin/sulbactam, imipenem, and vancomycin in E. faecalis. Forty-six percent of the E. faecalis strains were resistant to levofloxacin, 47% were resistant to ciprofloxacin, and 58% were resistant to norfloxacin. E. faecalis strains were highly resistant to erythromycin (92%) and ftetracycline (96%). The risk factor analysis revealed that age intervals, the underlying diseases, catheterization, and the number of admissions did not increase the risk of ciprofloxacin resistance, whereas patients with hospital-acquired infection (odds ratio [OR], 18.15; 95% confidence interval [CI], 3.46 to 95.13; p=0.001), patients who were treated in a urological department (OR, 6.15; 95% CI, 1.5 to 25.41; p=0.012), and patients who were transferred from health care centers (OR, 7.393; 95% CI, 1.32 to 41.22; p=0.023) had an increased risk of ciprofloxacin resistance compared with the matched controls. Conclusions Ciprofloxacin is no longer a recommended therapy for E. faecalis from complicated UTI in men with risk factors. We suggest that ampicillin/sulbactam can be recommended as alternatives for treating ciprofloxacin-resistant E. faecalis strains associated with UTI in Korea.

Expressions of Uroplakins in the Mouse Urinary Bladder with Cyclophosphamide-Induced Cystitis

Even though uroplakins (UPs) are believed to serve a strong protective barrier against toxic materials, cyclophosphamide (CP) causes extensive cystitis. We investigated the expression of UPs in the urothelium in CP induced mouse cystitis. A total of 27 ICR female mice received a single intraperitoneal injection of 200 mg CP/kg. Nine CP-treated mice and 6 controls were sequentially killed at 12, 24, and 72 hr post injection. Extensive cystitis and an increased vesical weight were seen. These all peaked within 12 hr post injection and they tended to decrease thereafter. The level of all the UPs mRNA, the protein expressions of UP II and III on immunoblotting study, and the expression of UP III on immunolocalization study were maximally suppressed within 12 hr; this partially recovered at 24 hr, and this completely recovered at 72 hr post CP injection. In conclusion, CP reduced the expression of UPs. The reduction of the UPs mRNA and protein was time dependent, and this peaked within 12 hr after CP injection. However, the damage was rapidly repaired within 24 hr. This study demonstrates a dynamic process, an extensive reduction and rapid recovery, for the UPs expression of the mouse urinary bladder after CP injection.

Acute effects of serotonin on rat bladder contractility

Introduction: The purpose of this study is to investigate in vitro the effects of serotonin on the rat detrusor. In particular, it examines which drugs inhibit the serotonin-induced detrusor contractions. Materials and Methods: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a force transducer. Acute effects of serotonin (0.0001–0.01 mM) on resting tension were assessed. Electrical field stimulation (EFS); bethanechol (0.0001–0.01 mM); ATP (1–3 mM)- or KCl (63.5–254 mM)-induced contractions using an application in an organ bath were compared with serotonin-induced contractions. In order to examine the action mechanism of serotonin-induced stimulation, EFS-, bethanechol-, ATP- or KCl-induced contraction on serotonin treatment (0.001 mM) was assessed and serotonin (0.001–0.1 mM) was cumulatively added to the organ bath following preincubation with propranolol, ketanserin, tropisetron, propiverine, sodium nitroprusside or doxazosin. Results: The serotonin-induced response has two phases: an initial transient contraction and a prolonged tonic phase. Serotonin produced a reversible and dose-dependent contraction of the detrusor strips. Responses to bethanechol significantly increased with a concentration of 0.001 mM serotonin (p < 0.05). There was no effect on the responses to ATP, KCl, or EFS on 0.001 mM serotonin. The 5-HT2 receptor is mainly responsible for serotonin-induced contractions of the detrusor (p < 0.05), while the 5-HT1 receptor is partially responsible. Doxazosin and propiverine each significantly suppressed the response to serotonin, while sodium nitroprusside and tropisetron each had no effect (p < 0.05). Conclusions: Because the 5-HT2 antagonist blocked the effect of serotonin-induced bladder contractions and the stimulation of the adrenoreceptors, the 5-HT2 antagonist seems to improve lower urinary tract symptoms.

Uroplakins in the Lower Urinary Tract

The apical surface of mammalian urinary epithelium is covered by numerous scallop-shaped membrane plaques. This plaque consists of four different uroplakins (UPs) and integral membrane proteins. UPs, which are a member of the tetraspanin superfamily, are assembled into plaques that act as an exceptional barrier to water and toxic materials in urine. Within the plaques, the four UPs are organized into two heterodimers consisting of UP Ia/UP II and UP Ib/UP III in the endoplasmic reticulum. The two heterodimers bind to a heterotetramer, and then assemble into 16-nm particles in the Golgi apparatus. The aggregated UP complex ultimately covers almost all the mature fusiform vesicles in cytoplasm. These organelles migrate towards the apical urothelial cells, where they can fuse with the apical plasma membrane. As a result, the UPs are synthesized in large quantities only by terminally differentiated urothelial cells. For this reason, the UPs can be regarded as a major urothelial differentiation marker. In UP knockout (KO) mice, the incorporation of fully assembled UP plaques in cytoplasm into the apical surface is not functional. The mice with UP III-deficient urothelium show a significantly reduced number of UPs, whereas those with UP II-deficient urothelium have nearly undetectable levels of UPs. This finding strongly suggests that UP II ablation completely abolishes plaque formation. In addition, UP II KO mice contain abnormal epithelial polyps or complete epithelial occlusion in their ureters. UP IIIa KO mice are also associated with impairment of the urothelial permeability barrier and development of vesicoureteral reflux as well as a decrease in urothelial plaque size. In this review, I summarize recently published studies about UPs and attempt to explain the clinical significance of our laboratory results.

49,XXXXY Syndrome with Diabetes Mellitus

49,XXXXY syndrome is a rare sex chromosome aneuploidy and characterized by mental retardation, skeletal defects, craniofacial anomalies and hypogonadism. The increased frequency of diabetes mellitus in patients with Klinefelter syndrome and other types of X-chromosome polysomy has been reported, but no cases of diabetes mellitus in adult with 49,XXXXY syndrome have been reported so far. We report an 18-year-old patient with 49,XXXXY syndrome accompanying diabetes mellitus.

The presence of Chlamydia is associated with increased leukocyte counts and pain severity in men with chronic pelvic pain syndrome.

OBJECTIVE To examine the role of urinary chlamydial infection in patients with chronic prostatitis and/or chronic pelvic pain syndrome (CP-CPPS). METHODS We recruited men aged 18-55 years over 4 years. We excluded patients with acute urethritis and any acute genitourinary infections. The participants evaluated their CP-CPPS-like symptoms with the Korean version National Institutes of Health-Chronic Prostatitis Symptom Index questionnaires. We measured white blood cell (WBC) counts in expressed prostatic secretion (EPS). In-house nucleic acid amplification test for Chlamydia trachomatis and Neisseria gonorrhoeae detection and WBC counts were performed from the patients first-voided urine. RESULTS A total of 765 eligible men were classified into 3 groups: 196 in non-CP-CPPS, 410 in noninflammatory CP-CPPS, and 159 in inflammatory CP-CPPS groups. The chlamydia-infected men showed higher pain, poor quality of life (QOL), and total scores in National Institutes of Health-Chronic Prostatitis Symptom Index questionnaires than the negative men (P = .041 for pain; P = .043 for QOL, and P = .027 for total). Multivariate analysis found that urinary chlamydial infection increased the risk of WBC count ≥16 in EPS (adjusted odds ratio [OR], 2.189; 95% confidence interval [CI], 1.021-4.690; P = .044) and WBC count between 2 and 4 in urine (OR, 5.227; 95% CI, 2.503-10.918; P = .001). In addition, chlamydial infection also increased the risk of inflammatory CP-CPPS than the non-CP-CPPS group (OR, 2.448; 95% CI, 1.010-5.932; P = .044), whereas the patients with noninflammatory CP-CPPS were not affected (OR, 1.6557; 95% CI, 0.738-3.717; P = .221). CONCLUSION Urinary chlamydial infection increased the pain scores and WBC counts in EPS and worsens the QOL in the patients with CP-CPPS.

Virulence Characteristics and Phylogenetic Background of Ciprofloxacin Resistant Escherichia coli in the Urine Samples from Korean Women with Acute Uncomplicated Cystitis

To clarify the characteristics of the virulence factors (VFs) of ciprofloxacin resistant Escherichia coli (CFRE) with acute uncomplicated cystitis (AUC), we determined the VFs and the phylogenetic background of all 54 CFRE strains and the 55 randomly selected ciprofloxacin sensitive E. coli strains (CFSE) from patients with AUC in 22 Korean hospitals. The prevalence of the VFs was as follows: fimA, papEF, papGIII, sfaI, dafaBC, cnf1, and hlyA were presented in 96%, 54%, 68%, 91%, 49%, 72%, and 29% of the samples, respectively. The expressions of papEF, cnf1, and hlyA were significantly more prevalent in the CFSE. Moreover, the expressions of cnf, and papEF significantly reduced the risk of ciprofloxacin resistance. The CFSE was also marginally associated with the group B2 (P=0.05). Although the presence of pyuria and a previous cystitis history were not related with the phylotyping and the expressions of VFs, group B2, and fimA and papEF were more expressed in the younger age patients (P<0.05). In conclusion, the CFRE exhibits a selective loss of VFs and the non-B2 phylotype in Korean AUC patients. The group B2 and the presence of fimA and papEF are associated with a younger age of AUC patients.

A Prospective Korean Multicenter Study for Infectious Complications in Patients Undergoing Prostate Surgery: Risk Factors and Efficacy of Antibiotic Prophylaxis

This multicenter study was undertaken to determine the efficacy of antibiotic prophylaxis and identify the risk factors for infectious complications after prostate surgery in Korean patients. A total of 424 patients who underwent surgery of the prostate were reviewed. All patients underwent urinalysis and urine culture preoperatively and postoperatively. Efficacy of antibiotic prophylaxis and risk factors for infectious complications were investigated. Infectious complications were observed in 34.9% of all patients. Factors independently associated with infectious complications were diabetes mellitus (adjusted OR, 1.99; 95% CI, 1.09-3.65, P=0.025) and operation time (adjusted OR, 1.08; 95% CI, 1.03-1.13, P=0.004). Clinicians should be aware of the high risk of infectious complications in patients with diabetes and those who undergo a prolonged operation time. Neither the type nor duration of prophylactic antibiotics resulted in differences in infectious complications. Graphical Abstract