Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
1.
J Infect Chemother ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38570137

RESUMO

We aimed to assess the accuracy of BD Phoenix for determining carbapenem susceptibility because we observed a decline in carbapenem susceptibility rate from the biannual cumulative data, after we transitioned to the BD Phoenix form Vitek 2 system. Between October 2021 and May 2022, we collected 82 non-duplicated Enterobacterales showing non-susceptible to at least one of the three carbapenems by BD Phoenix. We performed the broth microdilution (BMD) and disk diffusion (DD) according to the CLSI guideline. Compared to BMD, the categorical agreements for ertapenem (ERT), imipenem (IPM) and meropenem (MEPM) was 58.8%, 56.8% and 91.5% for BD Phoenix and it was 85.4%, 89.0%, and 97.6%, respectively, for DD (p value; 0.0001 for ERT and IPM, p value; 0.17 for MEPM). The major errors/minor errors for ERT, IPM, and MEPM were 14.0%/31.7%, 2.94%/40.7%, and 2.56%/6.10%, respectively for BD Phoenix, compared to 0%/14.6%, 0%/9.8%, and 0%/2.5%, for DD. While errors in the BD Phoenix showed tendency towards resistance, those in DD displayed no tendency towards either resistance or susceptibility. With DD, 21 out of the 27 isolates showing susceptible/intermediate/susceptible pattern (ERT/IPM/MEPM) and 13 out of the 16 isolates showing intermediate/susceptible/susceptible pattern (ERT/IPM/MEPM), were correctly categorized by DD. However, for 22 isolates showing resistant/susceptible/susceptible pattern (ERT/IPM/MEPM), only 13 isolates were correctly categorized by DD. In conclusion, to mitigate the risk of overcalling carbapenem non-susceptibility with BD Phoenix, it will be helpful to perform a complementary test using DD and to provide comments on the DD results to clinicians.

2.
Vox Sang ; 119(4): 353-362, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38245834

RESUMO

BACKGROUND AND OBJECTIVES: Decreased or loss of ABO blood group antigen expression has been observed in acute myeloid leukaemia (AML) patients. We studied the clinical significance of this group in AML patients. MATERIALS AND METHODS: This was a retrospective, single-centre cohort study in which the data were retrieved from April 2009 to December 2019. A total of 1592 AML patients with normal ABO blood group antigen (Group I) and 65 patients of decreased or loss of ABO blood group antigen (Group II) group were enrolled. Data were collected at the time of initial admission for pathological diagnosis. To interrogate the underlying mechanism, publicly available The Cancer Genome Atlas AML data were downloaded. RESULTS: Group II consisted of 3.9% (65/1657) of AML patients. The 90-day survival (D90) probability was higher for Group II with a mean survival of 86.4 days compared to 80.6 days for Group I (p = 0.047). Group II had higher haematocrit (28.6 vs. 27.4%) and lower d-dimer, fibrinogen degradation production and C-reactive protein. Publicly available data revealed that among 11 CpG methylation sites within the ABO gene, 4 sites with elevated methylation level were associated with improved D90 survival probability and demonstrated an inverse correlation with ABO gene expression. Lower expression of the ABO gene showed improved survival trends for D90 (p = 0.058) and 180-day survival (p = 0.072). CONCLUSION: AML with decreased expression or loss of ABO blood group showed better early survival during D90. Transfusion support for this subgroup of AML patients should be meticulously performed considering serum typing.


Assuntos
Sistema ABO de Grupos Sanguíneos , Leucemia Mieloide Aguda , Humanos , Estudos Retrospectivos , Sistema ABO de Grupos Sanguíneos/genética , Estudos de Coortes , Relevância Clínica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia
3.
J Clin Apher ; 38(6): 727-737, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37786990

RESUMO

BACKGROUND: The association between leukapheresis (LK) as a treatment option for hyperleukocytosis (HL) in patients with acute myeloid leukemia (AML) remains controversial. METHODS: Data were extracted from the electronic medical record for 2801 patients with AML between April 2009 and December 2019. LK was performed when the leukocyte count was ≥100 × 109 /L at the time initial bone marrow examination. RESULTS: A comparison between the patients with HL in the non-LK (n = 1579) and LK (n = 208) groups revealed survival probabilities (%) of 93.2% and 90.4% (P = .130) for day 30 (D30), 85.4% and 84.2% (P = .196) for D60, and 83.6% and 80.8% (P = .258) for D90, respectively. After propensity score matching, a comparison between the patients with HL in the non-LK (n = 192) and LK (n = 192) groups revealed survival probabilities (%) of 83.9% and 91.2% (P = .030) for D30, 75.0% and 84.9% (P = .015) for day 60 (D60), and 62.4% and 81.3% (P = .034) for day 90 (D90), respectively. After D150, the observed effect of LK appeared to be mitigated without a survival benefit. DISCUSSION: LK was associated with improved early survival outcomes at D30, D60, and D90 among patients with AML exhibiting HL. Thus, it may be considered a treatment option for reducing cell mass in such patients.


Assuntos
Leucemia Mieloide Aguda , Leucocitose , Humanos , Estudos de Coortes , Leucocitose/terapia , Leucaférese , Pontuação de Propensão , Leucemia Mieloide Aguda/terapia
4.
J Clin Med ; 12(18)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37762881

RESUMO

Acute myeloid leukemia (AML) is a clinical emergency requiring treatment and results in high 30-day (D30) mortality. In this study, the prediction of D30 survival was studied using a machine learning (ML) method. The total cohort consisted of 1700 survivors and 130 non-survivors at D30. Eight clinical and 42 laboratory variables were collected at the time of diagnosis by pathology. Among them, six variables were selected by a feature selection method: induction chemotherapy (CTx), hemorrhage, infection, C-reactive protein, blood urea nitrogen, and lactate dehydrogenase. Clinical and laboratory data were entered into the training model for D30 survival prediction, followed by testing. Among the tested ML algorithms, the decision tree (DT) algorithm showed higher accuracy, the highest sensitivity, and specificity values (95% CI) of 90.6% (0.918-0.951), 70.4% (0.885-0.924), and 92.1% (0.885-0.924), respectively. DT classified patients into eight specific groups with distinct features. Group 1 with CTx showed a favorable outcome with a survival rate of 97.8% (1469/1502). Group 6, with hemorrhage and the lowest fibrinogen level at diagnosis, showed the worst survival rate of 45.5% (25/55) and 20.5 days. Prediction of D30 survival among AML patients by classification of patients with DT showed distinct features that might support clinical decision-making.

5.
Blood Res ; 58(S1): S1-S7, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36843378

RESUMO

Transfusion support for hematopoietic stem cell transplantation (HSCT) is an essential part of supportive care, and compatible blood should be transfused into recipients. As leukocyte antigen (HLA) matching is considered first and as the blood group does not impede HSCT, major, minor, bidirectional, and RhD incompatibilities occur that might hinder transfusion and cause adverse events. Leukocyte reduction in blood products is frequently used, and irradiation should be performed for blood products, except for plasma. To mitigate incompatibility and adverse events, local transfusion guidelines, hospital transfusion committees, and patient management should be considered.

6.
HLA ; 100(1): 52-58, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35484951

RESUMO

The effects of COVID-19 vaccination on alloimmunization and clinical impact in transplant candidates remain largely unknown. In a 61-year-old man who had no donor-specific antibodies (DSA) and was planned to undergo ABO-incompatible kidney transplantation (ABOi KT), DSAs (anti-A24, anti-B51, and anti-Cw14) developed after COVID-19 vaccination. After desensitization therapy, antibody level was further increased, leading to flow cytometric crossmatch-positive status. Donor-specific T cell immunity using interferon-gamma ELISPOT was continuously negative, whereas SARS-CoV-2 specific T cell immunity was intact. After confirming the C1q-negative status of DSA, the patient received ABOi KT. The patient had stable graft function and suppressed alloimmunity up to 2 months after KT. COVID-19 vaccination might relate to alloimmunization in transplant candidates, and desensitization through immune monitoring can help guide transplantation.


Assuntos
COVID-19 , Transplante de Rim , Alelos , Anticorpos , Vacinas contra COVID-19 , Citometria de Fluxo , Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos HLA , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinação
7.
ACS Omega ; 6(47): 31945-31954, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34870017

RESUMO

Hyperpigmentation is induced by the overactivation of tyrosinase, which is a rate-limiting enzyme in melanogenesis. The defatted extract of hemp (Cannabis sativa L.) seed is known to have inhibitory effects on melanogenesis; however, effective compounds in the extract have not been identified yet. In this study, three phenethyl cinnamamides present in hemp seed extract were prepared by purification and chemical synthesis and were assessed for their inhibitory effect on melanogenesis in B16F10 melanoma cells. A comparison of the anti-melanogenesis and anti-tyrosinase activity of hemp seed solvent fractions revealed that the ethyl acetate fraction possessed the greatest potential for suppressing melanogenesis in melanoma cells by decreasing tyrosinase activity. We tentatively identified 26 compounds in the ethyl acetate fraction by comparing spectroscopic data with the literature. Three phenethyl cinnamamides such as N-trans-caffeoyltyramine, N-trans-coumaroyltyramine, and N-trans-feruloyltyramine present abundantly in the ethyl acetate fraction were prepared and their anti-melanogenesis and anti-tyrosinase activities in melanoma cells were evaluated. We found that N-trans-caffeoyltyramine and N-trans-feruloyltyramine inhibited alpha melanocyte stimulating hormone (α-MSH)-induced melanogenesis without cytotoxicity, while N-trans-coumaroyltyramine inhibited melanogenesis with cytotoxicity. IC50 values of N-trans-caffeoyltyramine, N-trans-feruloyltyramine, and N-trans-coumaroyltyramine for inhibition of α-MSH-mediated tyrosinase activation were 0.8, 20.2, and 6.3 µM, respectively. Overall, N-trans-caffeoyltyramine possessed the strongest anti-melanogenesis activity among the three phenethyl cinnamamides evaluated. The inhibitory effect of N-trans-caffeoyltyramine was verified by determining the melanin content and tyrosinase activity in melanoma after treating the cells with synthetic compounds. Thus, N-trans-caffeoyltyramine isolated from hemp seed extract could be useful in cosmetics as a skin-whitening agent.

8.
PLoS One ; 16(8): e0255626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34339461

RESUMO

BACKGROUND: Alcohol use disorder (AUD) is a chronic disease with a higher recurrence rate than that of other mental illnesses. Moreover, it requires continuous outpatient treatment for the patient to maintain abstinence. However, with a low probability of these patients to continue outpatient treatment, predicting and managing patients who might discontinue treatment becomes necessary. Accordingly, we developed a machine learning (ML) algorithm to predict which the risk of patients dropping out of outpatient treatment schemes. METHODS: A total of 839 patients were selected out of 2,206 patients admitted for AUD in three hospitals under the Catholic Central Medical Center in Korea. We implemented six ML models-logistic regression, support vector machine, k-nearest neighbor, random forest, neural network, and AdaBoost-and compared the prediction performances thereof. RESULTS: Among the six models, AdaBoost was selected as the final model for recommended use owing to its area under the receiver operating characteristic curve (AUROC) of 0.72. The four variables affecting the prediction based on feature importance were the length of hospitalization, age, residential area, and diabetes. CONCLUSION: An ML algorithm was developed herein to predict the risk of patients with AUD in Korea discontinuing outpatient treatment. By testing and validating various machine learning models, we determined the best performing model, AdaBoost, as the final model for recommended use. Using this model, clinicians can manage patients with high risks of discontinuing treatment and establish patient-specific treatment strategies. Therefore, our model can potentially enable patients with AUD to successfully complete their treatments by identifying them before they can drop out.


Assuntos
Alcoolismo/epidemiologia , Algoritmos , Aprendizado de Máquina , Pacientes Ambulatoriais/psicologia , Medição de Risco/métodos , Adulto , Alcoolismo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Curva ROC , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto Jovem
9.
ACS Omega ; 5(48): 30946-30955, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33324802

RESUMO

Hyperpigmentation resulting from the overactivation of tyrosinase leads to darker spots or patches on the human skin. Although these phenomena are harmless, there is still great demand for melanogenesis inhibitors to prevent hyperpigmentation by inhibiting the tyrosinase, a rate-limiting enzyme in melanogenesis. Although Lepisorus thunbergianus has been used in folk remedies as a diuretic and hemostatic agent, its effect on melanogenesis has not yet been reported. In this study, we prepared an L. thunbergianus extract and its solvent fractions and evaluated their biological activity against free radical and melanin synthesis. The extract of L. thunbergianus inhibited mushroom tyrosinase activity more efficiently than, and with similar antioxidant activity to, arbutin in vitro. Comparative evaluation of the anti-melanogenesis and anti-tyrosinase activity of L. thunbergianus solvent fractions demonstrated that, by inhibiting tyrosinase activity, the butanol fraction has the highest potential for the inhibition of melanogenesis in melanoma cells. We found by structural analysis using high-performance liquid chromatography (HPLC) and NMR spectroscopy that the major compounds in butanol fraction were three caffeoylquinic acid derivatives. The three derivatives had similar radical scavenging and anti-tyrosinase activities in vitro, while only 5-caffeoylquinic acid had an inhibitory effect on α-MSH-induced melanogenesis. The inhibitory effect of 5-caffeoylquinic acid was verified by the determination of the melanin content and tyrosinase activity in melanoma after treating the cells with a commercial compound. Further, we revealed that 5-caffeoylquinic acid inhibited melanogenesis by chelating a copper cation from a copper-tyrosinase complex. Thus, 5-caffeoylquinic acid or butanol fraction isolated from L. thunbergianus might be useful in cosmetics as a skin-whitening agent.

10.
Chem Res Toxicol ; 33(8): 2120-2129, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32635723

RESUMO

Human Y-family DNA polymerase (pol) ι is involved in translesion DNA synthesis (TLS) and base excision repair (BER) of oxidative DNA damage. Genetic variations may alter the function of pol ι and affect cellular susceptibility to oxidative genotoxic agents, but their effects remain unclear. We investigated the impacts of 10 human missense germline variations on pol ι function by biochemical and cell-based assays. Both polymerase and deoxyribose phosphate (dRP) lyase activities were determined utilizing recombinant pol ι (residues 1-445) proteins. The K209Q, K228I, and Q386R variants showed 4- to 53-fold decreases in specificity constants (kcat/Km) for dCTP insertion opposite G and 8-oxo-7,8-dihydroguanine compared to the wild-type. The R126C and K345E variants showed wild-type-like polymerase activity, although these two variants (as well as the R209Q, K228I, and Q386R variants) showed greater than 6-fold decreases in dRP lyase activity compared to the wild-type. A CRISPR/Cas9-mediated POLI knockout conferred higher sensitivity to H2O2 in human embryonic kidney (HEK293) cells. Exogenous expression of the full-length wild-type, R126C, and K345E variants fully rescued the H2O2 sensitivity in POLI-deficient cells, while full-length R209Q, K228I, and Q386R variants did not rescue the sensitivity. Our results indicate that the R126C and K345E variants (having wild-type-like polymerase activity, albeit impaired in dRP lyase activity) could fully rescue the H2O2 sensitivity in POLI-deficient cells, while the R209Q, K228I, and Q386R variants, all impaired in polymerase and dRP lyase activity, failed to rescue the sensitivity, indicating the relative importance of TLS-related polymerase function of pol ι rather than its BER-related dRP lyase function in protection from oxidative stress. The possibility exists that the hypoactive pol ι variants increase the individual susceptibility to oxidative genotoxic agents.


Assuntos
DNA Polimerase Dirigida por DNA/metabolismo , Peróxido de Hidrogênio/metabolismo , DNA Polimerase Dirigida por DNA/deficiência , DNA Polimerase Dirigida por DNA/genética , Células HEK293 , Humanos , Peróxido de Hidrogênio/análise , Modelos Moleculares , DNA Polimerase iota
11.
Psychiatry Res ; 275: 46-52, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878856

RESUMO

To provide appropriate solutions for problematic smartphone use, we need to first understand its types. This study aimed to identify types of problematic smartphone use based on psychiatric symptoms, using the decision tree method. We recruited 5,372 smartphone users from online surveys conducted between February 3 and February 22, 2016. Based on scores on the Korean Smartphone Addiction Proneness Scale for Adults (S-Scale), 974 smartphone users were assigned to the smartphone-dependent group and 4398 users were assigned to the normal group. The data-mining technique of C5.0 decision tree was applied. We used 15 input variables, including demographic and psychological factors. Four psychiatric variables emerged as the most important predictors: self-control (Sc; 66%), anxiety (Anx; 25%), depression (Dep; 7%), and dysfunctional impulsivities (Imp; 3%). We identified the following five types of problematic smartphone use: (1) non-comorbid, (2) self-control, (3) Sc + Anx, (4) Sc + Anx + Dep, and (5) Sc + Anx + Dep + Imp. We found that 74% of smartphone-dependent users had psychiatric symptoms. The ratio of participants belonging to the non-comorbid and self-control types was 64%. We proposed that these types of problematic smartphone use may be used for the development of an appropriate service for controlling and preventing such behaviors in adults.


Assuntos
Ansiedade/psicologia , Comportamento Aditivo/psicologia , Depressão/psicologia , Comportamento Impulsivo , Autocontrole/psicologia , Smartphone , Adulto , Ansiedade/diagnóstico , Comportamento Aditivo/diagnóstico , Depressão/diagnóstico , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Autorrelato/normas , Inquéritos e Questionários/normas , Adulto Jovem
12.
J Healthc Eng ; 2018: 4651582, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755715

RESUMO

Object: Pathologic prediction of prostate cancer can be made by predicting the patient's prostate metastasis prior to surgery based on biopsy information. Because biopsy variables associated with pathology have uncertainty regarding individual patient differences, a method for classification according to these variables is needed. Method: We propose a deep belief network and Dempster-Shafer- (DBN-DS-) based multiclassifier for the pathologic prediction of prostate cancer. The DBN-DS learns prostate-specific antigen (PSA), Gleason score, and clinical T stage variable information using three DBNs. Uncertainty regarding the predicted output was removed from the DBN and combined with information from DS to make a correct decision. Result: The new method was validated on pathology data from 6342 patients with prostate cancer. The pathology stages consisted of organ-confined disease (OCD; 3892 patients) and non-organ-confined disease (NOCD; 2453 patients). The results showed that the accuracy of the proposed DBN-DS was 81.27%, which is higher than the 64.14% of the Partin table. Conclusion: The proposed DBN-DS is more effective than other methods in predicting pathology stage. The performance is high because of the linear combination using the results of pathology-related features. The proposed method may be effective in decision support for prostate cancer treatment.


Assuntos
Aprendizado Profundo , Diagnóstico por Computador/métodos , Estadiamento de Neoplasias/métodos , Próstata/patologia , Neoplasias da Próstata , Biópsia , Humanos , Masculino , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia
13.
J Healthc Eng ; 20172017.
Artigo em Inglês | MEDLINE | ID: mdl-29076332

RESUMO

Background: Of the machine learning techniques used in predicting coronary heart disease (CHD), neural network (NN) is popularly used to improve performance accuracy. Objective: Even though NN-based systems provide meaningful results based on clinical experiments, medical experts are not satisfied with their predictive performances because NN is trained in a "black-box" style. Method: We sought to devise an NN-based prediction of CHD risk using feature correlation analysis (NN-FCA) using two stages. First, the feature selection stage, which makes features acceding to the importance in predicting CHD risk, is ranked, and second, the feature correlation analysis stage, during which one learns about the existence of correlations between feature relations and the data of each NN predictor output, is determined. Result: Of the 4146 individuals in the Korean dataset evaluated, 3031 had low CHD risk and 1115 had CHD high risk. The area under the receiver operating characteristic (ROC) curve of the proposed model (0.749 ± 0.010) was larger than the Framingham risk score (FRS) (0.393 ± 0.010). Conclusions: The proposed NN-FCA, which utilizes feature correlation analysis, was found to be better than FRS in terms of CHD risk prediction. Furthermore, the proposed model resulted in a larger ROC curve and more accurate predictions of CHD risk in the Korean population than the FRS.

14.
J Healthc Eng ; 2017: 2780501, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29065583

RESUMO

BACKGROUND: Of the machine learning techniques used in predicting coronary heart disease (CHD), neural network (NN) is popularly used to improve performance accuracy. OBJECTIVE: Even though NN-based systems provide meaningful results based on clinical experiments, medical experts are not satisfied with their predictive performances because NN is trained in a "black-box" style. METHOD: We sought to devise an NN-based prediction of CHD risk using feature correlation analysis (NN-FCA) using two stages. First, the feature selection stage, which makes features acceding to the importance in predicting CHD risk, is ranked, and second, the feature correlation analysis stage, during which one learns about the existence of correlations between feature relations and the data of each NN predictor output, is determined. RESULT: Of the 4146 individuals in the Korean dataset evaluated, 3031 had low CHD risk and 1115 had CHD high risk. The area under the receiver operating characteristic (ROC) curve of the proposed model (0.749 ± 0.010) was larger than the Framingham risk score (FRS) (0.393 ± 0.010). CONCLUSIONS: The proposed NN-FCA, which utilizes feature correlation analysis, was found to be better than FRS in terms of CHD risk prediction. Furthermore, the proposed model resulted in a larger ROC curve and more accurate predictions of CHD risk in the Korean population than the FRS.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Redes Neurais de Computação , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/etiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Curva ROC , República da Coreia/epidemiologia , Medição de Risco , Fatores de Risco
15.
Stud Health Technol Inform ; 245: 1273, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29295358

RESUMO

This study objectives to investigate a range of Partin table and several machine learning methods for pathological stage prediction and assess them with respect to their predictive model performance based on Koreans data. The data was used SPCDB and gathered records from 944 patients treated with tertiary hospital. Partin table has low accuracy (65.68%) when applied on SPCDB dataset for comparison on patients with OCD NOCD conditions. SVM (75%) represents a promising alternative to Partin table from which pathology staging can benefit.


Assuntos
Aprendizado de Máquina , Estadiamento de Neoplasias , Neoplasias da Próstata , Humanos , Masculino , Nomogramas , Valor Preditivo dos Testes
16.
Chem Res Toxicol ; 29(10): 1741-1754, 2016 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-27603496

RESUMO

DNA polymerase (pol) κ efficiently catalyzes error-free translesion DNA synthesis (TLS) opposite bulky N2-guanyl lesions induced by carcinogens such as polycyclic aromatic hydrocarbons. We investigated the biochemical effects of nine human nonsynonymous germline POLK variations on the TLS properties of pol κ, utilizing recombinant pol κ (residues 1-526) enzymes and DNA templates containing an N2-CH2(9-anthracenyl)G (N2-AnthG), 8-oxo-7,8-dihydroguanine (8-oxoG), O6-methyl(Me)G, or an abasic site. In steady-state kinetic analyses, the R246X, R298H, T473A, and R512W variants displayed 7- to 18-fold decreases in kcat/Km for dCTP insertion opposite G and N2-AnthG, with 2- to 3-fold decreases in DNA binding affinity, compared to that of the wild-type, and further showed 5- to 190-fold decreases in kcat/Km for next-base extension from C paired with N2-AnthG. The A471V variant showed 2- to 4-fold decreases in kcat/Km for correct nucleotide insertion opposite and beyond G (or N2-AnthG) compared to that of the wild-type. These five hypoactive variants also showed similar patterns of attenuation of TLS activity opposite 8-oxoG, O6-MeG, and abasic lesions. By contrast, the T44M variant exhibited 7- to 11-fold decreases in kcat/Km for dCTP insertion opposite N2-AnthG and O6-MeG (as well as for dATP insertion opposite an abasic site) but not opposite both G and 8-oxoG, nor beyond N2-AnthG, compared to that of the wild-type. These results suggest that the R246X, R298H, T473A, R512W, and A471V variants cause a general catalytic impairment of pol κ opposite G and all four lesions, whereas the T44M variant induces opposite lesion-dependent catalytic impairment, i.e., only opposite O6-MeG, abasic, and bulky N2-G lesions but not opposite G and 8-oxoG, in pol κ, which might indicate that these hypoactive pol κ variants are genetic factors in modifying individual susceptibility to genotoxic carcinogens in certain subsets of populations.


Assuntos
DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Variação Genética/genética , Humanos , Modelos Moleculares , Conformação Molecular
17.
Chem Res Toxicol ; 29(3): 367-79, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26914252

RESUMO

The Y-family DNA polymerase REV1 is involved in replicative bypass of damaged DNA and G-quadruplex (G4) DNA. In addition to a scaffolding role in the replicative bypass, REV1 acts in a catalytic role as a deoxycytidyl transferase opposite some replication stall sites, e.g., apurinic/apyrimidinic (AP) sites, N(2)-guanyl lesions, and G4 sites. We characterized the biochemical properties of 12 reported germline missense variants of human REV1, including the N373S variant associated with high risk of cervical cancer, using the recombinant REV1 (residues 330-833) proteins and DNA templates containing a G, AP site, N(2)-CH2(2-naphthyl)G (N(2)-NaphG), or G4. In steady-state kinetic analyses, the F427L, R434Q, M656V, D700N, R704Q, and P831L variants displayed 2- to 8-fold decreases in kcat/Km for dCTP insertion opposite all four templates, compared to that of wild-type, while the N373S, M407L, and N497S showed 2- to 3-fold increases with all four and the former three or two templates, respectively. The F427L, R434Q, M656V, and R704Q variants also had 2- to 3-fold lower binding affinities to DNA substrates containing G, an AP site, and/or N(2)-NaphG than wild-type. Distinctively, the N373S variant had a 3-fold higher binding affinity to G4 DNA than the wild-type, as well as a 2-fold higher catalytic activity opposite the first tetrad G, suggesting a facilitating effect of this variation on replication of G4 DNA sequences in certain human papillomavirus genomes. Our results suggest that the catalytic function of REV1 is moderately or slightly altered by at least nine genetic variations, and the G4 DNA processing function of REV1 is slightly enhanced by the N373S variation, which might provide the possibility that certain germline missense REV1 variations affect the individual susceptibility to carcinogenesis by modifying the capability of REV1 for replicative bypass past DNA lesions and G4 motifs derived from chemical and viral carcinogens.


Assuntos
Dano ao DNA , DNA/química , DNA/metabolismo , Quadruplex G , Mutação em Linhagem Germinativa/genética , Mutação de Sentido Incorreto/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Adutos de DNA/química , Humanos , Modelos Moleculares , Proteínas Nucleares/química , Nucleotidiltransferases/química
18.
Comput Methods Programs Biomed ; 116(1): 10-25, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24837641

RESUMO

This paper proposes new combined methods to classify normal and epileptic seizure EEG signals using wavelet transform (WT), phase-space reconstruction (PSR), and Euclidean distance (ED) based on a neural network with weighted fuzzy membership functions (NEWFM). WT, PSR, ED, and statistical methods that include frequency distributions and variation, were implemented to extract 24 initial features to use as inputs. Of the 24 initial features, 4 minimum features with the highest accuracy were selected using a non-overlap area distribution measurement method supported by the NEWFM. These 4 minimum features were used as inputs for the NEWFM and this resulted in performance sensitivity, specificity, and accuracy of 96.33%, 100%, and 98.17%, respectively. In addition, the area under Receiver Operating Characteristic (ROC) curve was used to measure the performances of NEWFM both without and with feature selections.


Assuntos
Encéfalo/fisiopatologia , Diagnóstico por Computador/métodos , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Reconhecimento Automatizado de Padrão/métodos , Análise de Ondaletas , Algoritmos , Mapeamento Encefálico/métodos , Epilepsia/classificação , Redes Neurais de Computação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Korean Circ J ; 39(6): 223-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19949627

RESUMO

BACKGROUND AND OBJECTIVES: During coronary angiography and interventional procedures, catheters that are engaged in a coronary ostium are routinely flushed, typically with normal saline, to expel blood from the catheter or to inject a pharmacologic agent. Saline contains sodium and chloride ions. Such injections may affect the electrophysiologic properties of the myocardium; however, the effect of normal saline on ventricular repolarization has not been established in patients with variant angina. SUBJECTS AND METHODS: We studied 51 consecutive patients with variant angina. Five mL of normal saline (NS) or 5% dextrose solution (DW) were infused into the left coronary artery in random order. We measured the heart rate, QT interval, and T-wave amplitude using Mac-Lac 5.2. RESULTS: The baseline clinical characteristics were not different between the NS {n=30 (14 males); mean age, 56+/-10 years} and the 5% DW groups {n=21 (7 males); mean age, 59+/-10 years}. The changes in the mean corrected QT (QTc) interval were significantly increased at the time of infusion of NS compared to 5% DW (45.1+/-30.3 vs. 20.9+/-23.3 ms, p=0.004). There was a T-wave amplitude change >0.2 mV in at least one-lead in 27 patients (90.0%) during NS infusion compared to 7 patients (33.3%) during 5% DW infusions (p=0.001). No significant changes in heart rate and blood pressure were noted during of the infusions. CONCLUSION: NS was associated with prolongation of ventricular repolarization in patients with variant angina.

20.
Microbiol Immunol ; 51(3): 307-12, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17380050

RESUMO

This study revealed the presence of various rickettsial agents in mites from wild rodents collected in Southern Jeolla Province, Korea, by nested polymerase chain reaction (PCR) and sequence analysis of a partial citrate synthase and rickettsia outer membrane protein B genes. Rickettsial agents closely related to the Rickettsia species TwKM02, R. australis, and the Rickettsia species Cf15 were successfully identified in this study, for the first time in Korea, and R. japonica, R. akari, R. conorii, R. felis, and R. typhi were also detected, as previously described. The data presented in this paper extend knowledge on the geographic distribution of SFG rickettsiae in eastern Asia and it may necessary to consider the role of mites in rickettsial transmission.


Assuntos
Rickettsieae/genética , Trombiculidae/microbiologia , Animais , Coreia (Geográfico) , Filogenia , Reação em Cadeia da Polimerase/métodos , Rickettsieae/isolamento & purificação , Roedores/parasitologia , Análise de Sequência de DNA/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...