This study aimed to investigate the overall cumulative exposure-response and the lag response relationships between daily temperature and urolithiasis presentation in Seoul. Using a time-series design and distributing lag nonlinear methods, we estimated the relative risk (RR) of urolithiasis presentation associated with mean daily temperature, including the cumulative RR for a 20 days period, and RR for individual daily lag through 20 days. We analyzed data from 14,518 patients of 4 hospitals emergency department who sought medical evaluation or treatment of urolithiasis from 2005-2013 in Seoul. RR was estimated according to sex and age. Associations between mean daily temperature and urolithiasis presentation were not monotonic. Furthermore, there was variation in the exposure-response curve shapes and the strength of association at different temperatures, although in most cases RRs increased for temperatures above the 13℃ reference value. The RRs for urolothiasis at 29℃ vs. 13℃ were 2.54 in all patients (95% confidence interval [CI]: 1.67-3.87), 2.59 in male (95% CI, 1.56-4.32), 2.42 in female (95% CI, 1.15-5.07), 3.83 in male less than 40 years old (95% CI, 1.78-8.26), and 2.47 in male between 40 and 60 years old (95% CI, 1.15-5.34). Consistent trends of increasing RR of urolithiasis presentation were observed within 5 days of high temperatures across all groups. Urolithiasis presentation increased with high temperature with higher daily mean temperatures, with the strongest associations estimated for lags of only a few days, in Seoul, a metropolitan city in Korea.
Adult ; Age Factors ; Aged ; Databases, Factual ; Emergency Service, Hospital ; Female ; Humans ; Male ; Middle Aged ; Regression Analysis ; Republic of Korea ; Risk ; Seoul ; Sex Factors ; Temperature ; Time Factors ; Urolithiasis/diagnosis/epidemiology/*etiology

We investigated how the dual inhibition of the molecular mechanism of the mammalian target of the rapamycin (mTOR) downstreams, P70S6 kinase (P70S6K) and eukaryotic initiation factor 4E (eIF4E), can lead to a suppression of the proliferation and progression of urothelial carcinoma (UC) in an orthotopic mouse non-muscle invasive bladder tumor (NMIBT) model. A KU-7-luc cell intravesically instilled orthotopic mouse NMIBC model was monitored using bioluminescence imaging (BLI) in vivo by interfering with different molecular components using rapamycin and siRNA technology. We then analyzed the effects on molecular activation status, cell growth, proliferation, and progression. A high concentration of rapamycin (10 microM) blocked both P70S6K and elF4E phosphorylation and inhibited cell proliferation in the KU-7-luc cells. It also reduced cell viability and proliferation more than the transfection of siRNA against p70S6K or elF4E. The groups with dual p70S6K and elF4E siRNA, and rapamycin reduced tumor volume and lamina propria invasion more than the groups with p70S6K or elF4E siRNA instillation, although all groups reduced photon density compared to the control. These findings suggest that both the mTOR pathway downstream of eIF4E and p70S6K can be successfully inhibited by high dose rapamycin only, and p70S6K and Elf4E dual inhibition is essential to control bladder tumor growth and progression.
Animals ; Cell Line ; Cell Proliferation/drug effects/genetics ; Cell Survival/drug effects ; Disease Progression ; Eukaryotic Initiation Factor-4E/*antagonists & inhibitors/genetics ; Female ; Mice ; Mice, Nude ; Mucous Membrane/pathology ; Phosphorylation/drug effects ; RNA Interference ; RNA, Small Interfering ; Ribosomal Protein S6 Kinases, 70-kDa/*antagonists & inhibitors/genetics ; Signal Transduction/drug effects ; Sirolimus/*pharmacology ; TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Urinary Bladder Neoplasms/genetics/*pathology ; Urothelium/pathology

We investigated how the dual inhibition of the molecular mechanism of the mammalian target of the rapamycin (mTOR) downstreams, P70S6 kinase (P70S6K) and eukaryotic initiation factor 4E (eIF4E), can lead to a suppression of the proliferation and progression of urothelial carcinoma (UC) in an orthotopic mouse non-muscle invasive bladder tumor (NMIBT) model. A KU-7-luc cell intravesically instilled orthotopic mouse NMIBC model was monitored using bioluminescence imaging (BLI) in vivo by interfering with different molecular components using rapamycin and siRNA technology. We then analyzed the effects on molecular activation status, cell growth, proliferation, and progression. A high concentration of rapamycin (10 microM) blocked both P70S6K and elF4E phosphorylation and inhibited cell proliferation in the KU-7-luc cells. It also reduced cell viability and proliferation more than the transfection of siRNA against p70S6K or elF4E. The groups with dual p70S6K and elF4E siRNA, and rapamycin reduced tumor volume and lamina propria invasion more than the groups with p70S6K or elF4E siRNA instillation, although all groups reduced photon density compared to the control. These findings suggest that both the mTOR pathway downstream of eIF4E and p70S6K can be successfully inhibited by high dose rapamycin only, and p70S6K and Elf4E dual inhibition is essential to control bladder tumor growth and progression.
Animals ; Cell Line ; Cell Proliferation/drug effects/genetics ; Cell Survival/drug effects ; Disease Progression ; Eukaryotic Initiation Factor-4E/*antagonists & inhibitors/genetics ; Female ; Mice ; Mice, Nude ; Mucous Membrane/pathology ; Phosphorylation/drug effects ; RNA Interference ; RNA, Small Interfering ; Ribosomal Protein S6 Kinases, 70-kDa/*antagonists & inhibitors/genetics ; Signal Transduction/drug effects ; Sirolimus/*pharmacology ; TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Urinary Bladder Neoplasms/genetics/*pathology ; Urothelium/pathology

We found an error in our published article.

We established an orthotopic non-muscle invasive bladder cancer (NMIBC) mouse model expressing the mammalian target of the rapamycin (mTOR) signaling pathway. After intravesical instillation of KU-7-lucs (day 0), animals were subsequently monitored by bioluminescence imaging (BLI) on days 4, 7, 14, and 21, and performed histopathological examination. We also validated the orthotopic mouse model expressing the mTOR signaling pathway immunohistochemically. In vitro BLI photon density was correlated with KU-7-luc cell number (r2 = 0.97, P < 0.01) and in vivo BLI photon densities increased steadily with time after intravesical instillation. The tumor take rate was 84.2%, formed initially on day 4 and remained NMIBC up to day 21. T1 photon densities were significantly higher than Ta (P < 0.01), and histological tumor volume was positively correlated with BLI photon density (r2 = 0.87, P < 0.01). The mTOR signaling pathway-related proteins were expressed in the bladder, and were correlated with the western blot results. Our results suggest successful establishment of an orthotopic mouse NMIBC model expressing the mTOR signaling pathway using KU-7-luc cells. This model is expected to be helpful to evaluate preclinical testing of intravesical therapy based on the mTOR signaling pathway against NMIBC.
Animals ; Blotting, Western ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Genes, Reporter ; Green Fluorescent Proteins/genetics/metabolism ; Humans ; Immunohistochemistry ; Luciferases, Firefly/genetics ; Luminescent Measurements ; Mice ; Mice, Nude ; Neoplasm Staging ; *Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism ; Transplantation, Heterologous ; Urinary Bladder Neoplasms/*metabolism/pathology/veterinary

BACKGROUND: Alloimmunization of human platelet antigens (HPA) is associated with clinically significant disease, such as platelet refractoriness, neonatal alloimmune thrombocytopenia, or posttransfusion purpura. It is determined by single nucleotide polymorphism of genes for platelet membrane glycoprotein. To date, approximately 27 HPAs have been discovered, and their frequencies differ depending on ethnicity and country. METHODS: We conducted an investigation of prevalence of HPA in the Korean population using a multiplex single-base primer extension reaction (SNaPshot). With 84 specimens from healthy donors, HPA genotyping was performed on 11 different HPAs, including HPA-1, -2, -3, -4, -5, -6, -7, -8, -9, -13, and -15. RESULTS: A total of 90 blood samples were genotyped. The genotype frequencies of HPA were as follows: HPA-1a/1a: 100.0%, -2a/2a: 83.3%, -2a/2b: 14.3%, -2b/2b: 2.4%, -3a/3a: 39.3%, -3a/3b: 52.4%, -3b/3b: 8.3%, -4a/4a: 100.0%, -5a/5a: 95.2%, -5a/5b: 4.8%, -6a/6a: 94.0%, -6a/6b: 6.0%, -7a/7a: 100.0%, -8a/8a: 100.0%, -9a/9a: 97.6%, -9a/9b: 2.4%, -13a/13a: 100.0%, -15a/15a: 23.8%, -15a/15b: 51.2%, and -15b/15b: 25.0%. CONCLUSION: The SNaPshot assay was employed for detection of SNPs in various clinically significant HPA genes. In addition to well-known frequencies of previously reported HPA-1 to -8, this study showed frequencies of HPA-9, -13, and -15 in Koreans for the first time. The SNaPshot technique might be suitable for use in actual clinical testing in patients with platelet alloimmunization.
Antigens, Human Platelet ; Blood Platelets ; Genotype ; Humans ; Membrane Glycoproteins ; Polymorphism, Single Nucleotide ; Prevalence ; Purpura ; Purpura, Thrombocytopenic ; Thrombocytopenia, Neonatal Alloimmune ; Tissue Donors

PURPOSE: The aim of this study was to evaluate the effectiveness of simultaneous flexible ureteroscopic removal of stones (URS) for ureteral and ipsilateral renal stones and to analyze the predictive factors for renal stone-free status. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent simultaneous flexible URS of ureteral and ipsilateral renal stones from January 2010 to May 2012. All operations used a flexible ureteroscope. We identified 74 cases of retrograde intrarenal surgery and 74 ureteral stones (74 patients). Stone-free status was respectively defined as no visible stones and clinically insignificant residual stones <3 mm on a postoperative image study. Predictive factors for stone-free status were evaluated. RESULTS: The immediate postoperative renal stone-free rate was 70%, which increased to 83% at 1 month after surgery. The immediate postoperative ureteral stone-free rate was 100%. Among all renal stones, 15 (20.3%) were separately located in the renal pelvis, 11 (14.8%) in the upper calyx, 15 (20.3%) in the mid calyx, and 33 (44.6%) in the lower calyx. The mean cumulative stone burden was 92.22+/-105.75 mm2. In a multivariate analysis, cumulative stone burden <100 mm2 was a significant predictive factor for postoperative renal stone-free status after 1 month (p<0.01). CONCLUSIONS: Flexible URS can be considered simultaneously for both ureteral and renal stones in selected patients. Flexible URS is a favorable option that promises high stone-free status without significant complications for patients with a stone burden <100 mm2.
Humans ; Kidney Calculi ; Kidney Pelvis ; Lithotripsy ; Multivariate Analysis ; Retrospective Studies ; Treatment Outcome ; Ureter ; Ureteroscopes

There have been 5 case reports about immune hemolytic anemia related with cimetidine, but there has been no such report in Korea. A sixty-four-year-old woman was admitted to the emergency department in a coma. She was diagnosed with diffuse large B-cell lymphoma 5 years ago and she achieved a complete remission after treatment. She was in a state of shock, and her blood pressure was 70/40 mmHg. The laboratory test results were consistent with hemolytic anemia (HA) as follows: hemoglobin: 1.9 g/dL, corrected reticulocyte count: 2%, total/conjugated bilirubin: 6.4/2.1 mg/dL, lactate dehydrogenase: 1,083 U/L and haptoglobin <10 mg/dL. She had a history of taking the drugs including cimetidine, acetaminophen and etizolam for two days. She urgently received transfusion of 3 units of packed red blood cells and then she regained consciousness. To investigate the relation between cimetidine and HA, we subsequently performed a drug-induced immune complex test and an antibody test by using cimetidine, AB serum and phosphate-buffered saline. The results proved that cimetidine was the cause of the HA. Patient was treated with steroid, and the following laboratory tests showed rapid improvement. This is the first case report from Korea that shows the causal relationship between cimetidine and immune HA.
Acetaminophen ; Anemia, Hemolytic ; Antigen-Antibody Complex ; Blood Pressure ; Cimetidine ; Coma ; Consciousness ; Diazepam ; Emergencies ; Erythrocytes ; Female ; Haptoglobins ; Humans ; Korea ; Lactic Acid ; Lymphoma, B-Cell ; Reticulocytes ; Shock

Good's syndrome (thymoma with immunodeficiency) is a rare cause of combined B-cell and T-cell immunodeficiency in adults. We present here a case of Good's syndrome involving a 52 year-old man with an ABO blood group abnormality. He had undergone surgery for thymoma with myasthenia gravis 27 years ago. He also had a history of pulmonary tuberculosis, herpes zoster and pure red cell aplasia. On admission, he was suspected of having pneumonia, and S. pneumoniae was isolated from blood culture. The immunoglobulin levels were markedly decreased. Lymphocyte subset analysis revealed the absence of CD19+ B cells. The result of ABO typing showed a normal strong reaction on the cell typing, but a relatively weak reaction on the serum typing. Therefore, we performed ABO genotyping to confirm his ABO type, which was revealed to be B/O1 . This case suggests that ABO typing should be performed when the diagnosis of Good's syndrome is made. Moreover, Good's syndrome (thymoma with hypogammaglobulinemia) should be considered and evaluated for in patients with a weak ABO reverse type.
Adult ; B-Lymphocytes ; Herpes Zoster ; Humans ; Immunoglobulins ; Lymphocyte Subsets ; Myasthenia Gravis ; Pneumonia ; Red-Cell Aplasia, Pure ; T-Lymphocytes ; Thymoma ; Tuberculosis, Pulmonary

BACKGROUND: Anti-K is one of the most significant unexpected antibodies that cause hemolytic transfusion reactions. Individuals with anti-K have to be transfused with K antigen-negative red cells. Although Koreans rarely have the K antigen, we have detected three cases of anti-K and we analyzed the Kell blood group genotypes for the KEL*1/KEL*2 alleles at the same time. METHODS: We analyzed the KEL*1/KEL*2 allele genotypes from 261 blood donors at Seoul National University Bundang Hospital. Kell genotyping were carried out using polymerase chain reaction (PCR) and restriction enzyme length polymorphism (RFLP). Identification of anti-K was performed using three kinds of methods; 37degrees C albumin, an anti-human globulin phase tube, a bead cassette and a gel card. Three cases of anti-K also underwent PCR with a sequence specific primer (SSP) for Kell genotyping. For comparison, the KEL*1 allele (698C>T) was synthesized by site-directed-mutagenesis. RESULTS: All 261 donors were KEL*2/KEL*2 homozygotes and a digested KEL*1 allele was not found. The three patients with anti-K were also KEL*2/KEL*2 homozygotes and the reactivities of the anti-K identification test were the same. CONCLUSION: The KEL gene frequency for the KEL*1/KEL*2 allele corresponded with that of the Kell phenotype, as was previously reported. We experienced three cases of anti-K and two out of the three were assumed that they had been transfused with the K antigen-positive blood of foreigners. This study revealed that the possibility of anti-K alloimmunization and hemolytic transfusion reactions cannot be excluded in Koreans.
Alleles ; Antibodies ; Antigens, Bacterial ; Antigens, Surface ; Blood Donors ; Blood Group Incompatibility ; Emigrants and Immigrants ; Gene Frequency ; Genotype ; Homozygote ; Humans ; Phenotype ; Polymerase Chain Reaction ; Tissue Donors