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1.
Investig Clin Urol ; 63(1): 42-52, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983122

RESUMO

PURPOSE: To develop and evaluate the performance of a polygenic risk score (PRS) constructed in a Korean male population to predict clinically significant prostate cancer (csPCa). MATERIALS AND METHODS: Total 2,702 PCa samples and 7,485 controls were used to discover csPCa susceptible single nucleotide polymorphisms (SNPs). Males with biopsy-proven or post-radical prostatectomy Gleason score 7 or higher were included for analysis. After genotype imputation for quality control, logistic regression models were applied to test association and calculate effect size. Extracted candidate SNPs were further tested to compare predictive performance according to number of SNPs included in the PRS. The best-fit model was validated in an independent cohort of 311 cases and 822 controls. RESULTS: Of the 83 candidate SNPs with significant PCa association reported in previous literature, rs72725879 located in PRNCR1 showed the highest significance for PCa risk (odds ratio, 0.597; 95% confidence interval [CI], 0.555-0.641; p=4.3×10-45). Thirty-two SNPs within 26 distinct loci were further selected for PRS construction. Best performance was found with the top 29 SNPs, with AUC found to be 0.700 (95% CI, 0.667-0.734). Males with very-high PRS (above the 95th percentile) had a 4.92-fold increased risk for csPCa. CONCLUSIONS: Ethnic-specific PRS was developed and validated in Korean males to predict csPCa susceptibility using the largest csPCa sample size in Asia. PRS can be a potential biomarker to predict individual risk. Future multi-ethnic trials are required to further validate our results.


Assuntos
Herança Multifatorial , Neoplasias da Próstata/genética , Idoso , Estudos de Coortes , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
2.
Sci Rep ; 11(1): 18389, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526524

RESUMO

To investigate the association between pelvic floor muscle strength and erectile function in a prospectively collected observational cohort. 270 male volunteers were prospectively collected and grouped by International Index of Erectile Function-5 (IIEF-5) scores. Pelvic floor muscle strength was compared. Patients with obvious neurologic deficits, abnormal pelvic bones, history of pelvic radiation therapy, prostatectomy, or urinary incontinence were excluded. We analyzed 247 patients with mean (± standard deviation, SD) age of 62.8 (± 10.1) years. Mean (± SD) maximal and average strength were 2.0 (± 1.5) and 1.1 (± 0.8) kgf, respectively. Mean (± SD) endurance and IIEF-5 scores were 7.2 (± 2.6) seconds and 13.3 (± 7.9), respectively. Patients with IIEF-5 scores ≤ 12 tended to be older, with a higher occurrence of hypertension and lower body mass index. Age [odds ratio (OR) 1.08, 95% confidence interval (CI) 1.04-1.12, p < 0.001], and maximal strength < 1.9 kgf (OR 2.62, 95% CI 1.38-4.97, p = 0.003) were independent predictors for IIEF-5 scores ≤ 12 in multivariate regression analysis. Patients with erectile dysfunction were older and showed lower pelvic floor muscle maximal strength. Future prospective trials needed for using physiotherapy are required to verify our results.


Assuntos
Força Muscular , Diafragma da Pelve/fisiologia , Ereção Peniana , Adulto , Idoso , Índice de Massa Corporal , Disfunção Erétil/diagnóstico , Disfunção Erétil/etiologia , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Dinamômetro de Força Muscular , Estudos Prospectivos
3.
Investig Clin Urol ; 62(4): 477-484, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34085790

RESUMO

PURPOSE: To identify the prevalence of detrusor overactivity with impaired contractility (DOIC) in the community-dwelling elderly and explore whether it is from a single or two independent bladder dysfunctions. MATERIALS AND METHODS: Based on a 10-year urodynamic database of the SEOUL Study Group, elderly patients who met inclusion criteria were selected. Bladder sensation, capacity, and compliance were designated as evaluation elements for storage function, and free maximal flow rate (Qmax) and post void residual volume, detrusor pressure at maximal flow (PdetQmax), and bladder voiding efficiency for voiding function. RESULTS: The prevalence rate of DOIC was 18.8% and 5.5% among 2,571 men and 688 women, respectively, and increased significantly with age. In men, patients with DOIC showed no differences in storage parameters and significantly lower free Qmax and PdetQmax among voiding parameters, compared to those with detrusor overactivity (DO) only. Compared to men with detrusor underactivity (DU) only, those with DOIC had worse parameters in the majority of storage and voiding functions. In women, most of the storage and voiding functions were worse in patients with DOIC than in those with DO only. On the other hand, women with DU showed lower PdetQmax and worse voiding functions than those with DOIC, although some parameters did not reach statistical significance. CONCLUSIONS: It seems that DOIC is developed from a coincidental combination of two independent DO and DU in men. In contrast, DOIC is likely to be an intermediate step during the process of progression from DO to DU in women.


Assuntos
Sintomas do Trato Urinário Inferior/fisiopatologia , Bexiga Urinária Hiperativa/fisiopatologia , Bexiga Urinária/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Contração Muscular , Músculo Liso/fisiopatologia , Prevalência , República da Coreia/epidemiologia , Fatores Sexuais , Bexiga Urinária Hiperativa/complicações , Bexiga Urinária Hiperativa/epidemiologia , Micção , Urodinâmica
4.
Investig Clin Urol ; 62(3): 256-266, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33943048

RESUMO

Decreasing costs of genetic testing and interest in disease inheritance has changed the landscape of cancer prediction in prostate cancer (PCa), and guidelines now include genetic testing for high-risk groups. Familial and hereditary PCa comprises approximately 20% and 5% of all PCa, respectively. Multifaceted disorders like PCa are caused by a combinatory effect of rare genes of high penetrance and smaller genetic variants of relatively lower effect size. Polygenic risk score (PRS) is a novel tool utilizing PCa-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association study (GWAS) to generate an additive estimate of an individual's lifetime genetic risk for cancer. However, most PRS are developed based on GWAS collected from mainly European populations and do not address ethnic differences in PCa genetics. This review highlights the attempts to generate a PRS tailored to Asian males including data from Korea, China, and Japan, and discuss the clinical implications for prediction of early onset and aggressive PCa.


Assuntos
/genética , Predisposição Genética para Doença/genética , Neoplasias da Próstata/genética , China , Estudo de Associação Genômica Ampla , Humanos , Japão , Masculino , Polimorfismo de Nucleotídeo Único/genética , República da Coreia
5.
Int Neurourol J ; 25(2): 150-156, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33387990

RESUMO

PURPOSE: This study aimed to evaluate the accuracy and reliability of a new smartphone-based acoustic uroflowmetry compared to conventional uroflowmetry. METHODS: This was a prospective validation study enrolling 128 subjects from September 2017 to April 2018 comparing a novel acoustic uroflowmetry to conventional uroflowmetry in an outpatient urologic clinic at Seoul National University Bundang Hospital. Visual comparison of flow patterns and uroflow parameters such as maximum flow rate (Qmax), average flow rate (Qavg), and voided volume were compared between the 2 techniques. Reliability and accuracy of the uroflowmetry results were compared using Pearson correlation coefficient (PCC) and Student t-test, respectively. RESULTS: One hundred twelve participants were included in the study. Of these, 77 had baseline urologic comorbidities while 35 were normal participants. Flow patterns between the 2 uroflowmetry techniques demonstrated strong visual correlation. When compared to conventional uroflowmetry, all 3 parameters of voiding in male participants showed a very robust correlation with PCC of 0.88, 0.91, and 0.95 for Qmax, Qavg, and voided volume, respectively. Among female participants, we observed a PCC of 0.78, 0.93, and 0.96 for Qmax, Qavg, and voided volume, respectively. The Qmax showed a statistically significant difference in both sexes between the 2 methods, although the absolute value was small. CONCLUSION: Uroflowmetry using acoustic analysis demonstrates comparable findings to conventional uroflowmetry. This provides an opportunity to perform uroflowmetry in the clinic or at home in a reliable, inexpensive manner. Future large-scale prospective studies are required to further validate our results.

6.
Investig Clin Urol ; 62(1): 32-38, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258324

RESUMO

PURPOSE: To describe a single-center 15-year experience of active surveillance (AS) for prostate cancer (PCa). MATERIALS AND METHODS: We retrospectively reviewed patients who underwent AS between 2003 and 2018. One hundred fifty-three patients were selected according to the following criteria: (1) biopsy Gleason pattern ≤3+4 with (2) ≤two positive core(s) and (3) ≤50% core involvement, clinical-stage ≤T2a, and prostate-specific antigen (PSA) ≤20 ng/mL. Follow-up included PSA measurement every six months, prostate biopsies at one year and then every 2-3 years, and MRI every year. Intervention was triggered by (1) Gleason score (GS) upgrading, (2) >two positive cores, or (3) PSA doubling-time in <3 years. RESULTS: Mean (±standard deviation) follow-up was 36.4 (±31.9) months. Ninety-three (60.8%) and 20 (13.1%) patients received second and third biopsies, respectively. Seventy-two patients (47.1%) discontinued AS for various reasons (59, intervention; 13, follow-up loss). Reasons for intervention consisted of GS upgrading (42.4%), >two positive cores (8.5%), abnormal PSA kinetics (11.9%), and patient preference (37.3%). Notably, 12 (25.5%) patients had pathologic GS ≥4+3 (unfavorable disease) and 3 (6.4%) patients had pathologic stage ≥T3a at radical prostatectomy. Median time to treatment-free survival was 19.5 months. Of the 59 patients who switched to intervention, biochemical recurrence was reported in only one (0.7%) patient. CONCLUSIONS: AS is an available option for low-risk PCa in carefully selected patients. Further larger prospective studies are needed to determine the optimal criteria for AS, especially in Korean PCa patients.


Assuntos
Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Conduta Expectante , Adulto , Idoso , Biópsia , Progressão da Doença , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Próstata/patologia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
7.
Front Oncol ; 10: 583625, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194723

RESUMO

AIMS: The purpose of this study is to evaluate an aggregate influence of prostate cancer (PCa) susceptibility variants on the development of PCa in Korean men by using the polygenic risk score (PRS) approach. METHODS: An analysis of 1,001 cases of PCa and 2,641 controls was performed to: (i) identify potential PCa-related risk loci in Koreans and (ii) validate the cumulative association between these loci and PCa using the PRS. Subgroup analyses based on risk stratification were conducted to better characterize the potential correlation to key PCa-related clinical outcomes (e.g., Gleason score, prostate-specific antigen levels). The results were replicated using 514 cases of PCa and 548 controls from an independent cohort. RESULTS: Genome-wide association analysis from our discovery cohort revealed 11 candidate single-nucleotide polymorphisms (SNPs) associated with PCa showing statistical significance of p < 5.0 × 10-5. Seven variants were located at 8q24.21 (rs1016343, rs16901979, and rs13252298 in PRNCR1; rs4242384, rs7837688, and rs1447295 in CASC8; and rs1512268 in NKX3). Two variants located within HNF1B (rs7501939 and rs4430796) had a significant negative association with PCa risk [odds ratio (OR) = 0.717 and 0.747, p = 6.42 × 10-7 and 3.67 × 10-6, respectively]. Of the six independent SNPs that remained after linkage disequilibrium (LD) pruning, the top four SNPs best predicted PCa risk with an area under the receiver operating characteristic curve (AUC) of 0.637 (95% CI: 0.582-0.692). Those with top 25% polygenic risk had a 4.2-fold increased risk of developing PCa compared with those with low risk. CONCLUSION: Eleven PCa risk variants in Korean men were identified; PRSs of a subset of these variants could help predict PCa susceptibility.

8.
Micromachines (Basel) ; 11(9)2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32872581

RESUMO

We measured and analyzed the Hall offset voltages in InGaZnO thin-film transistors. The Hall offset voltages were found to decrease monotonously as the electron densities increased. We attributed the magnitude of the offset voltage to the misalignment in the longitudinal distance between the probing points and the electron density to Fermi energy of the two-dimensional electron system, which was verified by the coincidence of the Hall voltage with the perpendicular magnetic field in the tilted magnetic field. From these results, we deduced the combined conduction band edge energy profiles from the Hall offset voltages with the electron density variations for three samples with different threshold voltages. The extracted combined conduction band edge varied by a few tens of meV over a longitudinal distance of a few tenths of µm. This result is in good agreement with the value obtained from the analysis of percolation conduction.

9.
J Cancer Res Clin Oncol ; 145(11): 2863-2870, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31501983

RESUMO

PURPOSE: To determine the association between lymphovascular invasion (LVI) and upper tract urothelial carcinoma (UTUC) among patients who underwent radical nephroureterectomy (RNU). MATERIALS AND METHODS: From 2003 and 2018, retrospective data of 453 patients treated for UTUC with open, laparoscopic, or robotic RNU were collected. Pathological specimens were assessed for LVI through hematoxylin and eosin staining. According to presence of LVI, patients were stratified into two groups and compared for perioperative characteristics. Kaplan-Meier analysis was used to assess progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Uni- and multivariate Cox regression models were used to find significance of LVI to survival. RESULTS: LVI was present in 132 (29.1%) of patients and was associated with higher age and lower preoperative GFR. Pathological outcomes included significantly higher tumor grade, higher rates of lymph node invasion and more positive surgical margins. During median 23.2 months follow-up (mean 37.1 months), 59.2% (n = 268) of total patients had tumor recurrence, with highest incidences in lymph nodes (51.5%). 5-year PFS, CSS, and OS were estimated at 35.4%, 94.6%, and 91.1% in LVI-negative patients and 17.2%, 75.1%, and 70.8% in LVI-positive patients, respectively (all p < 0.001). Multivariate analysis showed LVI to be an independent predictor of PFS (HR = 1.480; p = 0.018). CONCLUSION: LVI is an independent predictor of adverse PFS and is associated with poor CSS and OS in patients undergoing RNU for UTUC. These results may guide clinicians in selecting patients for adjuvant chemotherapy. Future prospective trials are necessary to further validate our results.


Assuntos
Linfonodos/patologia , Vasos Linfáticos/patologia , Recidiva Local de Neoplasia/mortalidade , Nefroureterectomia/mortalidade , Neoplasias Urológicas/mortalidade , Idoso , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Urológicas/patologia , Neoplasias Urológicas/cirurgia
10.
Sci Rep ; 9(1): 9834, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285480

RESUMO

Surfactants during routine washing have a tremendous effect on lipid loss from hair. This study aims to understand the loss of lipids from hair upon contact with surfactants and develop a way to prevent the lipid loss. The change in lipid levels depends on the relative hydrophobicity of the lipid. We herein propose that the change in lipid levels can be protected by two modifications. In the case of fatty acids and cholesterol (group A), the concentration difference between virgin hair versus surface modified hair with highly charged polymer was 22 to 32% higher after washing with surfactants while the loss of squalene and wax esters (group B) in response to surfactants still occurred even after the surface modification. In the hair treated by internal modification with the carbodiimide reaction, 52.0 to 81.3% more lipids in group B were prevented than in the untreated hair. Finally, different types of lipids were successfully protected by surface and internal modifications from the surfactant treatment. This study will be the basis for understanding the mechanisms by which surfactants damage the lipid barrier of tissues including hair and for establishing strategies to defend the barrier.


Assuntos
Cabelo/química , Lipídeos/análise , Tensoativos/efeitos adversos , Cabelo/efeitos dos fármacos , Cabelo/ultraestrutura , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Microscopia de Força Atômica
11.
Sci Rep ; 9(1): 6588, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036883

RESUMO

We investigated the lateral distribution of the equilibrium carrier concentration (n0) along the channel and the effects of channel length (L) on the source-drain series resistance (Rext) in the top-gate self-aligned (TG-SA) coplanar structure amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). The lateral distribution of n0 across the channel was extracted using the paired gate-to-source voltage (VGS)-based transmission line method and the temperature-dependent transfer characteristics obtained from the TFTs with different Ls. n0 abruptly decreased with an increase in the distance from the channel edge near the source/drain junctions; however, much smaller gradient of n0 was observed in the region near the middle of the channel. The effect of L on the Rext in the TG-SA coplanar a-IGZO TFT was investigated by applying the drain current-conductance method to the TFTs with various Ls. The increase of Rext was clearly observed with an increase in L especially at low VGSs, which was possibly attributed to the enhanced carrier diffusion near the source/drain junctions due to the larger gradient of the carrier concentration in the longer channel devices. Because the lateral carrier diffusion and the relatively high Rext are the critical issues in the TG-SA coplanar structure-based oxide TFTs, the results in this work are expected to be useful in further improving the electrical performance and uniformity of the TG-SA coplanar structure oxide TFTs.

12.
Medicine (Baltimore) ; 98(12): e14854, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30896629

RESUMO

OBJECTIVES: To investigate a way to reduce infectious complication after transrectal ultrasonography-guided prostate biopsy (TRUS-Bx), we planned a randomized trial to determine whether the use of the povidone-iodine suppository is effective in preventing infectious complications. METHODS: This study prospectively assessed 250 patients who underwent TRUS-Bx during December 2014 and May 2016. Clinical questionnaire responses and safety were evaluated. Povidone-iodine suppository after glycerin enema was performed 1 to 2 hours before TRUS-Bx. Both groups received the prophylactic antibiotics (ceftriaxone 2.0 g) 30 to 60 minutes before TRUS-Bx. No antibiotics were prescribed after TRUS-Bx. RESULTS: The 120 were assigned in the treatment group using povidone-iodine suppository and 130 were assigned in the control group. There was no significant difference of clinicopathologic features including age, prostate-specific antigen and cancer detection rate in both groups (P > .05). No infectious and non-infectious complications were reported in both groups. Povidone-iodine suppository-related side effects were not reported. No significant differences in international prostate symptom score, sexual health inventory for men score, and European Organization for Research and Treatment of Cancer Quality of Life questionnaire scores were found between the 2 groups (P > .05). No changes in each questionnaire scores between before and after TRUS-Bx were observed. CONCLUSIONS: Despite satisfying the predefined sample size, we could not prove the hypothesis that the use of povidone-iodine suppositories after TRUS-Bx would reduce infectious complications. A large-scale, multicenter, prospective study is needed to fully evaluate the clinical efficacy and safety of povidone-iodine suppository prior to TRUS-Bx.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Antibioticoprofilaxia/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Povidona-Iodo/administração & dosagem , Próstata/patologia , Idoso , Anti-Infecciosos Locais/efeitos adversos , Ceftriaxona/administração & dosagem , Ceftriaxona/efeitos adversos , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Povidona-Iodo/efeitos adversos , Estudos Prospectivos , Supositórios
13.
Sci Rep ; 8(1): 16154, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30385826

RESUMO

Mature biofilms are highly resistant to antimicrobial agents due to the presence of extracellular polymeric substances (EPS), which inhibit the penetration of external molecules. In this study, we developed a coordination compound consisting of zinc chloride and erythritol that exhibits penetrating and bactericidal activity against Streptococcus mutans biofilms. An in vitro biofilm model was established in microplates, and bactericidal activity against biofilms was evaluated using an Alamar blue assay. The cause of the antimicrobial activity of the zinc-erythritol mixture on mature biofilms was demonstrated using fast atom bombardment-mass spectrometry, confocal laser scanning microscopy and atomic force microscopy. We demonstrated that zinc chloride spontaneously formed cationic complexes with erythritol in water. The zinc-erythritol complexes reduced intra- and inter-molecular interactions between bacterial exopolysaccharides, a major component of EPS. This activity was confirmed by measuring the attenuation of the hardness of dried polysaccharides isolated from S. mutans biofilms. The reduction in the interactions between polysaccharides allowed the complexes to penetrate into biofilms and kill the embedded bacteria. While approximately 13% of biofilm-associated microbes were killed by a 10 min treatment with 6.6 mM zinc chloride, 45% were killed when a solution containing 19.8 mM erythritol and 6.6 mM zinc chloride was used. This strategy of leveraging the coordination properties of metal ions with sugar alcohols provides a simple way to effectively remove mature biofilms using only conventional substances without the need for intricate chemical synthesis processes.


Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Streptococcus mutans/efeitos dos fármacos , Anti-Infecciosos/química , Complexos de Coordenação/química , Humanos , Microscopia Confocal , Polissacarídeos/química , Polissacarídeos/farmacologia , Streptococcus mutans/patogenicidade , Álcoois Açúcares/química , Álcoois Açúcares/farmacologia , Zinco/química , Zinco/farmacologia
14.
Sci Rep ; 7(1): 8107, 2017 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-28808327

RESUMO

A biofilm, a community of microorganisms, is highly resistant to antibiotics, resulting in massive losses in various areas. We herein present a strategy to remove Streptococcus mutans biofilms through a spontaneous exfoliation by the synergistic effect between zwitterion and sugar alcohols. It is assumed that the anionic site of zwitterion can be coupled with sugar alcohols and the cationic site remains in the state of lacking electrons. The cationic site allows the complexes to be delivered to negatively charged exopolysaccharides of biofilms. This strategy facilitates a significant increase in the ability of sugar alcohols to disperse aggregated exopolysaccharides. In this work, it was demonstrated that the mixture of betaine and erythritol existed as a complex in water and that the complex induced a spontaneous detachment of biofilms from the surface to which the biofilms had been adhered. This detachment resulted from a reduction in adhesive forces of the biofilms due to an increase in solubility of bacterial exopolysaccharides. The effects triggered by the formation of complex between zwitterion and sugar alcohol provide a simple and safe way to remove biofilms without antibiotics and physical forces.


Assuntos
Streptococcus mutans/efeitos dos fármacos , Álcoois Açúcares/farmacologia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos
15.
Biochemistry ; 52(45): 7951-63, 2013 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-24171435

RESUMO

The primary (100 fs to 10 ns) and secondary (10 ns to 100 µs) photodynamics in the type II light-oxygen-voltage (LOV) domain from the blue light YtvA photoreceptor extracted from Bacillus subtilis were explored with transient absorption spectroscopy. The photodynamics of full-length YtvA were characterized after femtosecond 400 nm excitation of both the dark-adapted D447 state and the light-adapted S390 state. The S390 state relaxes on a 43 min time scale at room temperature back into D447, which is weakly accelerated by the introduction of imidazole. This is ascribed to an obstructed cavity in YtvA that hinders access to the embedded FMN chromophore and is more open in type I LOV domains. The primary photochemistry of dark-adapted YtvA is qualitatively similar to that of the type I LOV domains, including AsLOV2 from Avena sativa, but exhibits an appreciably higher (60% greater) terminal triplet yield, estimated near the maximal ΦISC value of ≈78%; the other 22% decays via non-triplet-generating fluorescence. The subsequent secondary dynamics are inhomogeneous, with three triplet populations co-evolving: the faster-decaying (I)T* population (38% occupancy) with a 200 ns decay time is nonproductive in generating the S390 adduct state, a slower (II)T* population (57% occupancy) exhibits a high yield (Φadduct ≈ 100%) in generating S390 and a third (5%) (III)T*population persists (>100 µs) with unresolved photoactivity. The ultrafast photoswitching dynamics of the S390 state appreciably differ from those previously resolved for the type I AcLOV2 domain from Adiantum capillus-veneris [Kennis, J. T., et al. (2004) J. Am. Chem. Soc. 126, 4512], with a low-yield dissociation (Φdis ≈ 2.5%) reaction, which is due to an ultrafast recombination reaction, following photodissociation, and is absent in AcLOV2, which results in the increased photoswitching activity of the latter domain.


Assuntos
Bacillus subtilis/metabolismo , Proteínas de Bactérias/química , Fotoquímica/métodos , Estrutura Secundária de Proteína
16.
Langmuir ; 29(41): 12710-9, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24024777

RESUMO

The adsorption and structure of sodium dodecyl sulfate (SDS) layers onto positively charged films have been monitored in situ with vibrational sum-frequency-generation (SFG) spectroscopy and surface plasmon resonance (SPR) sensing. Substrates with different charge densities and polarities used in these studies include CaF2 at different pH values as well as allylamine and heptylamine films deposited onto CaF2 and Au substrates by radio frequency glow discharge deposition. The SDS films were adsorbed from aqueous solutions ranging in concentration from 0.067 to 20 mM. In general the SFG spectra exhibited well resolved CH and OH peaks. However, at SDS concentrations between 1 and 8 mM the SFG CH and OH intensities decreased close to background levels. Combined data sets from molecular conformation, orientation, and order sensitive SFG with mass sensitive SPR suggest that the observed changes in SFG intensities above 0.2 mM are related to structural arrangements in the SDS layer. A model is proposed where the SFG intensity minimum between 1 and 8 mM is associated with a monolayer containing two headgroup orientations, one pointing toward the substrate and one pointing toward the solution phase. The SFG peaks observed at concentrations below 0.2 mM are dominated by the presence of adsorbed contaminants such as fatty alcohols (e.g., dodecanol), which are more surface active than SDS. As SDS solution concentration is increased above 1 mM SDS molecules are incorporated in the surface layer, with dodecanol continuing to be present in the surface layer for solution concentrations up to at least the critical micelle concentration.


Assuntos
Dodecilsulfato de Sódio/química , Adsorção , Fluoreto de Cálcio/química , Ouro/química , Concentração de Íons de Hidrogênio , Estrutura Molecular , Espectrofotometria Infravermelho , Ressonância de Plasmônio de Superfície , Propriedades de Superfície
17.
Korean J Urol ; 54(2): 89-94, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23549294

RESUMO

PURPOSE: The purpose of this study was to identify the risk factors for recatheterization after holmium laser enucleation of the prostate (HoLEP). MATERIALS AND METHODS: A total of 166 consecutive patients treated with HoLEP by a single surgeon from January 2010 to June 2011 were enrolled in this study. We collected data on preoperative and intraoperative parameters, including intraoperative bladder distention volume. The patients were divided into two groups. Group 1 included patients who voided successfully after removal of the catheter, and group 2 included patients who required recatheterization. Analysis and comparison of the perioperative parameters of both groups was performed for identification of risk factors for recatheterization. RESULTS: Recatheterization was required in 9 of 166 (5.4%) patients. No significant differences in age or preoperative parameters, including prostate-specific antigen, prostate volume, International Prostate Symptom Score, peak flow rate, postvoid residual urine, maximal bladder capacity, and Abrahams Griffiths number, were observed between the two groups. Of the intraoperative parameters, intraoperative bladder distention volume was significantly smaller in group 1 than in group 2 (700.65 mL vs. 897.78 mL, p<0.001). In the multivariate logistic regression analysis, after adjustment for other variables, intraoperative bladder distention volume was found to be a statistically significant risk factor for postoperative recatheterization (hazard ratio, 1.006; confidence interval, 1.002 to 1.010; p=0.002). CONCLUSIONS: Nine of 166 (5.4%) patients failed to void after HoLEP and required catheterization. Intraoperative bladder distention volume was found to be a statistically significant risk factor for recatheterization in this patient group.

19.
J Phys Chem A ; 115(16): 3905-16, 2011 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-21291184

RESUMO

The femtosecond to nanosecond dynamics of the all-trans ß-carotene carotenoid dissolved in 3-methylpentane is characterized and dissected with excitation-wavelength and temperature-dependent ultrafast dispersed transient absorption signals. The kinetics measured after red-edge (490 nm) and blue-edge (400 nm) excitation were contrasted under fluid solvent (298 K) and rigid glass (77 K) conditions. In all four measured data sets, the S* population kinetics was resolved prompting the development of a modified multicompartment model. The temperature-dependent and excitation wavelength-dependent S* quantum yield is ascribed to a competition of population surmounting a weak (55 cm(-1)) energy barrier on the S(2) state to favor S(1) generation and rapid internal conversion that favors S* generation. When cooled from room temperature to 77 K, the S* decay time scale shifted significantly from 30 to 400 ps, which is ascribed to small-scale structural relaxation with a 115 cm(-1) energy barrier. For the first time under low-energy excitation conditions, the triplet state is observed and confirmed to not originate from S* or S(1), but from S(2). The interconnectivity of the S* and S(1) populations is discussed, and no observed population flow is resolved between S* and S(1). Comparison of samples obtained from different laboratories with different purity levels demonstrates that sample contamination is not the primary origin of the S* state.


Assuntos
Teoria Quântica , beta Caroteno/química , Cristalografia por Raios X , Cinética , Modelos Moleculares , Conformação Molecular , Soluções , Temperatura
20.
Biochemistry ; 50(13): 2411-23, 2011 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-21323358

RESUMO

Phototropins, a class of light-activated protein kinases, are essential for several blue light responses in plants and algae, including phototropism. These proteins contain two internal light, oxygen, and voltage sensitive (LOV) domains, which bind flavin chromophores and undergo a reversible photochemical formation of a cysteinyl-flavin adduct as part of the light sensing process. While the photodynamic properties of such photosensory domains are dictated by interactions between the chromophore and surrounding protein, more distant residues can play a significant role as well. Here we explore the role of the Phe434 residue in the photosensory response of the second LOV domain of Avena sativa phototropin 1 (AsLOV2), a model photochemical system for these LOV domains. Phe434 is more than 6 Å from the FMN chromophore in AsLOV2; nevertheless, an F434Y point mutation is likely to change several structural features of the chromophore binding site, as we demonstrate using molecular dynamics simulations. Transient absorption signals spanning 15 decades in time were compared for wild-type AsLOV2 and the F434Y mutant, showing that the latter has significantly altered photodynamics, including (i) a faster intersystem crossing leading to triplet formation on a nanosecond time scale, (ii) biphasic formation of adduct-state kinetics on the microsecond time scale, and (iii) greatly accelerated ground-state recovery kinetics on a second time scale. We present mechanistic models that link these spectroscopic differences to changes in the configuration of the critical cysteine residue and in the chromophore's accessibility to solvent and oxygen according to MD trajectories and purging experiments. Taken together, these results demonstrate the importance of residues outside the chromophore-binding pocket in modulating LOV domain photodynamics.


Assuntos
Mononucleotídeo de Flavina/química , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Fototropinas/química , Fototropinas/metabolismo , Substituição de Aminoácidos , Avena/enzimologia , Sítios de Ligação , Biocatálise , Luz , Simulação de Dinâmica Molecular , Fototropinas/genética , Fototropinas/efeitos da radiação , Mutação Puntual , Estrutura Terciária de Proteína
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