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1.
Transfusion ; 64(5): 789-792, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38562113

RESUMO

BACKGROUND: We recently encountered a Rhnull phenotype proband within one family in the Chinese population. Rhnull is a rare autosomal recessive disorder characterized by the absence of the Rh antigens on the erythrocyte membrane, resulting in chronic hemolytic anemia. This study described the serological and molecular analysis of a Chinese Rhnull proband and his immediate family. METHODS: Red blood cells antigen phenotyping and antibody screening/identification were conducted. RHD, RHCE, and RHAG were analyzed using genomic DNA by polymerase chain reaction and sequence analysis. RESULTS: Serologic tests showed a D-C-E-c-e- phenotype in the proband associated with the suspicion of anti-Rh29 (titer 16). Molecular analyses showed a new mutation (c.406dupA) in exon 3 of RHAG. This duplication introduced a reading frameshift (p.Thr136AsnfsTer21). The RHAG mutation was found in the homozygous state for the proband and heterozygous state for his parents. CONCLUSION: We identified a novel RHAG mutation resulting in the Rhnull phenotype of the regulator type. Inheritance of the novel allele was shown by family study.


Assuntos
Mutação da Fase de Leitura , Fenótipo , Sistema do Grupo Sanguíneo Rh-Hr , Feminino , Humanos , Masculino , Proteínas Sanguíneas , População do Leste Asiático , Glicoproteínas de Membrana/genética , Linhagem , Sistema do Grupo Sanguíneo Rh-Hr/genética
2.
BMC Psychol ; 11(1): 391, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957764

RESUMO

BACKGROUND: As social networking sites (SNSs) with diverse functions gradually become an important social place for modern people, openness, as a personality trait that represents the willingness to consider diverse things, will be more likely to affect people's cognitive and emotional experience (e.g., social anxiety) in social interactions. This study examined the relationship between openness and social anxiety and the underlying psychological mechanism in the internet age based on the cognitive-behavioral model of social anxiety. METHODS: This cross­sectional survey study conducted a questionnaire survey of 522 college students from two provinces in China (191 male; age range 18-25; M = 20.76, SD = 1.34). RESULTS: The results showed that openness is negatively related to social anxiety. Self-evaluation and passive SNS use independently mediate the relationship between openness and social anxiety, respectively. Moreover, openness is associated with social anxiety both through the chain mediating roles of active SNS use and self-evaluation and through the chain mediating roles of passive SNS use and self-evaluation. CONCLUSIONS: Openness is negatively associated with social anxiety, and the different ways of SNS use and self-evaluation are the underlying mechanisms. These results provide insights into the clinical treatment of social anxiety and how to benefit from online interactions.


Assuntos
Autoavaliação Diagnóstica , Rede Social , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Estudos Transversais , Medo , Ansiedade
3.
ACS Sens ; 8(9): 3294-3306, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37607403

RESUMO

Over the past decade, super-resolution ultrasound localization microscopy (SR-ULM) has revolutionized ultrasound imaging with its capability to resolve the microvascular structures below the ultrasound diffraction limit. The introduction of this imaging technique enables the visualization, quantification, and characterization of tissue microvasculature. The early implementations of SR-ULM utilize microbubbles (MBs) that require a long image acquisition time due to the requirement of capturing sparsely isolated microbubble signals. The next-generation SR-ULM employs nanodroplets that have the potential to significantly reduce the image acquisition time without sacrificing the resolution. This review discusses various nanodroplet-based ultrasound localization microscopy techniques and their corresponding imaging mechanisms. A summary is given on the preclinical applications of SR-ULM with nanodroplets, and the challenges in the clinical translation of nanodroplet-based SR-ULM are presented while discussing the future perspectives. In conclusion, ultrasound localization microscopy is a promising microvasculature imaging technology that can provide new diagnostic and prognostic information for a wide range of pathologies, such as cancer, heart conditions, and autoimmune diseases, and enable personalized treatment monitoring at a microlevel.


Assuntos
Microscopia , Neoplasias , Humanos , Microscopia/métodos , Ultrassonografia/métodos , Microbolhas , Microvasos/diagnóstico por imagem
5.
Neural Regen Res ; 18(8): 1637-1644, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36751773

RESUMO

Myasthenia gravis is an acquired, humoral immunity-mediated autoimmune disease characterized by the production of autoantibodies that impair synaptic transmission at the neuromuscular junction. The intervention-mediated clearance of immunoglobulin G (IgG) was shown to be effective in controlling the progression of the disease. The neonatal Fc receptor (FcRn) plays a key role in prolonging the serum half-life of IgG. Antagonizing FcRn to prevent its binding to IgG can accelerate the catabolism of the latter, resulting in decreased levels of IgG, including pathogenic autoantibodies, thereby achieving a therapeutic effect. In this review, we detail the substantial research progress, both basic and clinical, relating to the use of FcRn inhibitors in the treatment of myasthenia gravis.

6.
Front Oncol ; 12: 1049991, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408165

RESUMO

Objective: Ultrasound imaging has been widely used in breast cancer screening. Recently, ultrasound super-resolution imaging (SRI) has shown the capability to break the diffraction limit to display microvasculature. However, the application of SRI on differential diagnosis of breast masses remains unknown. Therefore, this study aims to evaluate the feasibility and clinical value of SRI for visualizing microvasculature and differential diagnosis of breast masses. Methods: B mode, color-Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS) images of 46 patients were collected respectively. SRI were generated by localizations of each possible contrast signals. Micro-vessel density (MVD) and microvascular flow rate (MFR) were calculated from SRI and time to peak (TTP), peak intensity (PI) and area under the curve (AUC) were obtained by quantitative analysis of CEUS images respectively. Pathological results were considered as the gold standard. Independent chi-square test and multivariate logistic regression analysis were performed using these parameters to examine the correlation. Results: The results showed that SRI technique could be successfully applied on breast masses and display microvasculature at a significantly higher resolution than the conventional CDFI and CEUS images. The results showed that the PI, AUC, MVD and MFR of malignant breast masses were significantly higher than those of benign breast masses, while TTP was significantly lower than that of benign breast masses. Among all five parameters, MVD showed the highest positive correlation with the malignancy of breast masses. Conclusions: SRI is able to successfully display the microvasculature of breast masses. Compared with CDFI and CEUS, SRI can provide additional morphological and functional information for breast masses. MVD has a great potential in assisting the differential diagnosis of breast masses as an important imaging marker.

7.
Front Oncol ; 12: 978164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387122

RESUMO

Objective: Ultrasound imaging provides a fast and safe examination of thyroid nodules. Recently, the introduction of super-resolution imaging technique shows the capability of breaking the Ultrasound diffraction limit in imaging the micro-vessels. The aim of this study was to evaluate its feasibility and value for the differentiation of thyroid nodules. Methods: In this study, B-mode, contrast-enhanced ultrasound, and color Doppler flow imaging examinations were performed on thyroid nodules in 24 patients. Super-resolution imaging was performed to visualize the microvasculature with finer details. Microvascular flow rate (MFR) and micro-vessel density (MVD) within thyroid nodules were computed. The MFR and MVD were used to differentiate the benign and malignant thyroid nodules with pathological results as a gold standard. Results: Super-resolution imaging (SRI) technique can be successfully applied on human thyroid nodules to visualize the microvasculature with finer details and obtain the useful clinical information MVD and MFR to help differential diagnosis. The results suggested that the mean value of the MFR within benign thyroid nodule was 16.76 ± 6.82 mm/s whereas that within malignant thyroid was 9.86 ± 4.54 mm/s. The mean value of the MVD within benign thyroid was 0.78 while the value for malignant thyroid region was 0.59. MFR and MVD within the benign thyroid nodules were significantly higher than those within the malignant thyroid nodules respectively (p < 0.01). Conclusions: This study demonstrates the feasibility of ultrasound super-resolution imaging to show micro-vessels of human thyroid nodules via a clinical ultrasound platform. The important imaging markers, such as MVD and MFR, can be derived from SRI to provide more useful clinical information. It has the potential to be a new tool for aiding differential diagnosis of thyroid nodules.

8.
J Int Med Res ; 50(10): 3000605221123875, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36262051

RESUMO

OBJECTIVE: This study aimed to describe our experience of managing cesarean scar pregnancy (CSP) and outcomes depending on ultrasound imaging features. METHODS: A retrospective, cohort observational study was performed on 31 consecutive patients with CSP at 6 to 9 weeks of gestation from April 2015 to January 2021. All patients were evaluated for the residual myometrial thickness (RMT), growth direction of the gestational sac (GS), blood flow, and chorionic parenchyma using ultrasonography. Patients underwent curettage or methotrexate (MTX) combined with curettage in CSP depending on the age of the GS. Blood loss of >500 mL with curettage was considered major bleeding. RESULTS: Twenty-five (80.6%) patients had successful treatment, and six (19.4%) patients had major bleeding. The incidence of major bleeding was significantly higher in patients with >7 weeks of gestation, types II and III CSP, mixed and exogenous types of the growth direction of the GS, an RMT < 2 mm, and multiple lacunae formation in thickened chorionic parenchyma. CONCLUSIONS: The exogenous and mixed types of the GS, an RMT < 2 mm, and multiple lacunae in thickened chorionic parenchyma may be high-risk factors for major hemorrhage by curettage in CSP.


Assuntos
Cicatriz , Gravidez Ectópica , Gravidez , Feminino , Humanos , Cicatriz/diagnóstico por imagem , Cicatriz/etiologia , Metotrexato/uso terapêutico , Estudos Retrospectivos , Cesárea/efeitos adversos , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/etiologia , Gravidez Ectópica/cirurgia , Resultado do Tratamento
9.
Nanoscale Res Lett ; 17(1): 43, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35380290

RESUMO

OBJECTIVE: Even though extensive studies have surveyed long non-coding RNA (lncRNA)-related networks in hypoxic-ischemic brain damage (HIBD), the concrete function of lncRNA H19 (H19) in HIBD is still in ambiguity. Therein, this work intends to decipher H19-related network of microRNA (miR)-140-5p and signal transducer and activator of transcription 3 (STAT3) in HIBD. METHODS: Brain microvascular endothelial cells (BMECs) from BALB/c mice were isolated and induced by oxygen glucose deprivation (OGD). OGD-induced BMECs were transfected with depleted or restored H19, miR-140-5p or STAT3, and cell apoptosis, migration and angiogenesis were examined. H19, miR-140-5p and STAT3 expression and their internal connections were tested. RESULTS: H19 and STAT3 were overexpressed while miR-140-5p was down-regulated in OGD-induced BMECs. H19 or STAT3 knockdown, or miR-140-5p restoration repressed apoptosis and improved migration and angiogenesis of OGD-induced BMECs. MiR-140-5p restoration negated the impacts of up-regulated H19 on OGD-induced BMECs. H19 bound to miR-140-5p to modulate STAT3 expression. CONCLUSION: The work illustrates that depleting H19 or STAT3 or restoring miR-140-5p attenuates HIBD and supplies a novel perspective for HIBD management.

10.
Jpn J Nurs Sci ; 19(3): e12479, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35352471

RESUMO

AIM: To evaluate the effectiveness of a professional identity promotion strategy (PIPS) on nursing students' professional identity and resilience. METHODS: This study was a quasi-experimental study with a random cluster sample of 103 sophomore undergraduate nursing students. One hundred students answered the questionnaires at both baseline and follow-up (51 of 53 in the intervention group and 49 of 50 in the control group). Intervention and control groups underwent 5 months PIPS and standard professional education from May 2 to September 27, respectively. Participants completed the professional identity questionnaire for nursing students (PIQNS) and Connor-Davidson resilience scale (CD-RISC). Data were collected at baseline (T0), after the intervention (T1) and 3 months after the intervention (T2), and analyzed using the Chi-squared test, Fisher's exact test, and repeated-measures analysis of variance. RESULTS: There were no significant differences between the two groups (p > .05) regarding demographic questions, professional identity, or resilience at baseline (p > .05). Significant differences were found in professional identity between groups (p < .001), measurement times (p = .026), and in the interaction between groups and measurement times (p = .018) from T0 to T2. Significant differences were found in resilience between groups (p < .001), measurement times (p = .007), and in the interaction between groups and measurement times (p = .035) from T0 to T2. CONCLUSIONS: The PIPS program improved nursing students' professional identity and resilience. Further long-term effectiveness of the program needs to be tested with implementation through various forms of mobile technology.


Assuntos
COVID-19 , Bacharelado em Enfermagem , Estudantes de Enfermagem , COVID-19/prevenção & controle , Humanos , Pandemias , Inquéritos e Questionários
11.
Mol Plant ; 15(5): 805-819, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35063662

RESUMO

Magnesium (Mg2+), an essential structural component of chlorophyll, is absorbed from the soil by roots and transported to shoots to support photosynthesis in plants. However, the molecular mechanisms underlying root-to-shoot Mg2+ translocation remain largely unknown. We describe here the identification of four plasma membrane (PM)-localized transporters, named Mg2+ release transporters (MGRs), that are critical for root-to-shoot Mg transport in Arabidopsis. Functional complementation assays in a Mg2+-uptake-deficient bacterial strain confirmed that these MGRs conduct Mg2+ transport. PM-localized MGRs (MGR4, MGR5, MGR6, and MGR7) were expressed primarily in root stellar cells and participated in the xylem loading step of the long-distance Mg2+ transport process. In particular, MGR4 and MGR6 played a major role in shoot Mg homeostasis, as their loss-of-function mutants were hypersensitive to low Mg2+ but tolerant to high Mg2+ conditions. Reciprocal grafting analysis further demonstrated that MGR4 functions in the root to determine shoot Mg2+ accumulation and physiological phenotypes caused by both low- and high-Mg2+ stress. Taken together, our study has identified the long-sought transporters responsible for root-to-shoot Mg2+ translocation in plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transporte Biológico , Membrana Celular/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Xilema/metabolismo
12.
Chin Med J (Engl) ; 134(4): 415-424, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33617184

RESUMO

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION: Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Área Sob a Curva , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , China , Humanos , Curva ROC , Sensibilidade e Especificidade
13.
Ann Palliat Med ; 9(6): 4514-4521, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32692211

RESUMO

BACKGROUND: Shenzhen is a rapidly growing city in China with a population of over 11 million. The Hong Kong University-Shenzhen Hospital (HKU-SZH) was established in 2012 as a new model of publicly funded health care in mainland China. The clinical oncology center of the HKU-SZH was launched in 2013 which pledged to provide integrated palliative care for advanced cancer patients. This study aims to retrospectively analyze the quality of end-of-life care amongst patients with advanced cancer during their last hospitalization in the HKU-SZH. METHODS: Consecutive patients with advanced solid cancer who passed away in the HKU-SZH from March 2013 to February 2016 were analyzed. Clinical information regarding cancer diagnosis, anticancer treatments, and the aggressiveness of the treatment during the last month of life was recorded. The discussions on the Do-Not-Resuscitate (DNR) order with family members were reviewed. RESULTS: From March 2013 to February 2016, 441 patients with advanced solid cancer passed away in the HKU-SZH. A minority of them (9.3%, 41/441) received cytotoxic chemotherapy in the last month of life. Younger patients had high odds of receiving chemotherapy in their last month of life (OR 2.6, P=0.006). Those who received chemotherapy in their last month of life showed a trend of higher odds of admission to the intensive care unit (OR 2.94, P=0.08). The vast majority of family members / care providers (92.3%, 407/441) consented to the DNR order suggested by oncologists. The rate of DNR acceptance in this cohort was higher than previous reports from mainland China. Within HKU-SZH, the rate was higher in the oncology center than in other departments (OR 5.1, P<0.001). The use of chemotherapy in the last month of life did not associated with the acceptance of DNR (OR 1.3, P=0.23). CONCLUSIONS: The integrated oncology service of the new public hospital HKU-SZH achieved a satisfactory level of end-of-life care in patients with advanced cancer. Further studies are warranted to improve the early integration of palliative care service and to investigate the impact of palliative care on costeffectiveness of oncology service.


Assuntos
Neoplasias , Assistência Terminal , China , Hong Kong , Hospitais Públicos , Humanos , Neoplasias/terapia , Cuidados Paliativos , Estudos Retrospectivos
14.
Int J Colorectal Dis ; 34(8): 1349-1357, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31273449

RESUMO

BACKGROUND: This systematic review and meta-analysis seek to evaluate the prevalence of nodal disease in rectal cancer patients with pathological complete responses (pCR) after neoadjuvant chemoradiotherapy (ypT0N+). METHODS: This study conformed to the PRISMA guidelines. A search was performed on major databases to identify relevant articles. Meta-analyses of pooled proportions were performed on rectal cancer with pCR and ypT0N+. Meta-regression was undertaken to identify sources of heterogeneity, and the Newcastle-Ottawa Scale (NOS) was employed to assess the risk of bias. RESULTS: A total of 18 studies were included, totaling 7568 patients. The overall risk of bias was low, since all studies scored 6 and above out of 9 on the NOS. Preoperatively, the pooled proportions of patients with T3/T4 tumors and clinically positive nodal disease were 84.08% (95% CI 74.19 to 91.99%) and 52.14% (95% CI 35.02 to 69.00%) respectively. The prevalence of pCR in the whole pool was 18.52% (95% CI 13.31 to 24.35%; I2 = 93.85%; P = 0.00), and meta-regression showed a significantly negative relationship with patient age (ß = - 0.03, 95% CI - 0.03 to - 0.02; P = 0.00). The pooled prevalence of ypT0N+ was 4.61% (95% CI 2.41 to 7.28%; I2 = 52.27%; P = 0.01), and meta-regression demonstrated a significantly positive relationship with male gender (ß = 1.06, 95% CI 1.00 to 1.12; P = 0.04). CONCLUSION: There is a small risk of ypN+ in patients with pCR after neoadjuvant CRT and surgery for rectal cancer. However, further research is warranted to establish these findings and to identify predictive factors for this specific group of patients.


Assuntos
Quimiorradioterapia , Linfonodos/patologia , Terapia Neoadjuvante , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Resultado do Tratamento
15.
Sci Rep ; 9(1): 1463, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728384

RESUMO

Alarmins S100A8 and S100A9 are endogenous molecules released in response to environmental triggers and cellular damage. They are constitutively expressed in immune cells such as monocytes and neutrophils and their expression is upregulated under inflammatory conditions. The molecular mechanisms that regulate inflammatory pathways in tendinopathy are largely unknown therefore identifying early immune effectors is essential to understanding the pathology. Based on our previous investigations highlighting tendinopathy as an alarmin mediated pathology we sought evidence of S100A8 & A9 expression in a human model of tendinopathy and thereafter, to explore mechanisms whereby S100 proteins may regulate release of inflammatory mediators and matrix synthesis in human tenocytes. Immunohistochemistry and quantitative RT-PCR showed S100A8 & A9 expression was significantly upregulated in tendinopathic tissue compared with control. Furthermore, treating primary human tenocytes with exogenous S100A8 & A9 significantly increased protein release of IL-6, IL-8, CCL2, CCL20 and CXCL10; however, no alterations in genes associated with matrix remodelling were observed at a transcript level. We propose S100A8 & A9 participate in early pathology by modulating the stromal microenvironment and influencing the inflammatory profile observed in tendinopathy. S100A8 and S100A9 may participate in a positive feedback mechanism involving enhanced leukocyte recruitment and release of pro-inflammatory cytokines from tenocytes that perpetuates the inflammatory response within the tendon in the early stages of disease.


Assuntos
Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , Tendinopatia/metabolismo , Adolescente , Adulto , Animais , Estudos de Casos e Controles , Linhagem Celular , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Tendinopatia/genética , Regulação para Cima , Adulto Jovem
16.
Biochemistry ; 56(32): 4235-4243, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28714309

RESUMO

Blebbistatin is a potent and specific inhibitor of the motor functions of class II myosins, including striated muscle myosin and nonmuscle myosin-2 (NM2). However, the blebbistatin inhibition of NM2c has not been assessed and remains controversial with respect to its efficacy with smooth muscle myosin (SmM), which is highly homologous to NM2. To clarify these issues, we analyzed the effects of blebbistatin on the motor activities of recombinant SmM and three NM2s (NM2a, -2b, and -2c). We found that blebbistatin potently inhibits the actin-activated ATPase activities of SmM and NM2s with following IC50 values: 6.47 µM for SmM, 3.58 µM for NM2a, 2.30 µM for NM2b, and 1.57 µM for NM2c. To identify the blebbistatin-resistant myosin-2 mutant, we performed mutagenesis analysis of the conserved residues in the blebbistatin-binding site of SmM and NM2s. We found that the A456F mutation renders SmM and NM2s resistant to blebbistatin without greatly altering their motor activities or phosphorylation-dependent regulation, making A456F a useful mutant for investigating the cellular function of NM2s.


Assuntos
Proteínas Aviárias/antagonistas & inibidores , Proteínas Aviárias/química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Miosina não Muscular Tipo IIB/antagonistas & inibidores , Miosina não Muscular Tipo IIB/química , Miosinas de Músculo Liso/antagonistas & inibidores , Miosinas de Músculo Liso/química , Substituição de Aminoácidos , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Galinhas , Humanos , Camundongos , Mutação de Sentido Incorreto , Miosina não Muscular Tipo IIB/genética , Miosina não Muscular Tipo IIB/metabolismo , Miosinas de Músculo Liso/genética , Miosinas de Músculo Liso/metabolismo
17.
Mov Disord ; 31(12): 1905-1909, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27943471

RESUMO

OBJECTIVES: Mutations in RAB39B have been reported as a potential cause of X-linked Parkinson's disease (PD), a rare form of familial PD. We conducted a genetic analysis on RAB39B to evaluate whether RAB39B mutations are related to PD in the Chinese population. METHODS: In this study, 2 patients from an X-linked juvenile parkinsonism pedigree were clinically characterized and underwent whole-exome sequencing. A comprehensive screening for RAB39B mutations in 505 sporadic patients with PD and 510 healthy controls in a Chinese population was also performed. RESULTS: A novel mutation, c. 536dupA (p.E179fsX48), in RAB39B was identified in the juvenile parkinsonism pedigree. Brain MRI and CT scans in the 2 patients revealed calcification within the bilateral globus pallidus. No other potentially disease-causing RAB39B mutations were found in sporadic PD patients and controls. CONCLUSIONS: X-linked juvenile parkinsonism could be caused by a RAB39B mutation, and basal ganglia calcification may be a novel clinical feature of RAB39B-related parkinsonism. © 2016 International Parkinson and Movement Disorder Society.


Assuntos
Doenças dos Gânglios da Base/genética , Calcinose/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doença de Parkinson/genética , Transtornos Parkinsonianos/genética , Proteínas rab de Ligação ao GTP/genética , Adulto , Doenças dos Gânglios da Base/diagnóstico por imagem , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Linhagem
18.
Proc Natl Acad Sci U S A ; 113(40): E5812-E5820, 2016 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-27647889

RESUMO

The motor function of vertebrate myosin-5a is inhibited by its tail in a Ca2+-dependent manner. We previously demonstrated that the calmodulin (CaM) bound to the first isoleucine-glutamine (IQ) motif (IQ1) of myosin-5a is responsible for the Ca2+-dependent regulation of myosin-5a. We have solved the crystal structure of a truncated myosin-5a containing the motor domain and IQ1 (MD-IQ1) complexed with Ca2+-bound CaM (Ca2+-CaM) at 2.5-Å resolution. Compared with the structure of the MD-IQ1 complexed with essential light chain (an equivalent of apo-CaM), MD-IQ1/Ca2+-CaM displays large conformational differences in IQ1/CaM and little difference in the motor domain. In the MD-IQ1/Ca2+-CaM structure, the N-lobe and the C-lobe of Ca2+-CaM adopt an open conformation and grip the C-terminal and the N-terminal portions of the IQ1, respectively. Remarkably, the interlobe linker of CaM in IQ1/Ca2+-CaM is in a position opposite that in IQ1/apo-CaM, suggesting that CaM flip-flops relative to the IQ1 during the Ca2+ transition. We demonstrated that CaM continuously associates with the IQ1 during the Ca2+ transition and that the binding of CaM to IQ1 increases Ca2+ affinity and substantially changes the kinetics of the Ca2+ transition, suggesting that the IQ1/CaM complex functions as an intact Ca2+ sensor responding to distinct calcium signals.


Assuntos
Cálcio/metabolismo , Calmodulina/metabolismo , Miosina Tipo V/química , Miosina Tipo V/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Calmodulina/química , Calorimetria , Cristalografia por Raios X , Cinética , Camundongos , Modelos Biológicos , Domínios Proteicos , Coelhos , Espectrometria de Fluorescência , Homologia Estrutural de Proteína , Triptofano/metabolismo
19.
Ultrasound Med Biol ; 42(7): 1441-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27067416

RESUMO

This study aimed to explore the value of a real-time comparative observation method using contrast-enhanced ultrasound (CEUS) for discriminating between bronchial and pulmonary arterial phases in diagnosing lung diseases. Forty-nine patients with 50 pulmonary lesions (45 peripheral lesions and five central lesions with obstructive atelectasis, including 36 malignant tumors, five tuberculomas, four inflammatory pseudotumors and five pneumonia lesions) detected via computed tomography and visible on ultrasonography were enrolled in this study. The arterial phases were determined by comparing contrast agent arrival time (AT) in the peripheral lung lesion with that in adjacent lung tissue, referred to as a real-time comparative observation method. Detection rates of this observation method were 100% (50/50) for pulmonary arterial phase and 88% (44/50) for bronchial arterial phase. Using the instrument's built-in graphing and analysis software, a time-intensity curve was constructed based on a chosen region of interest within the lesion where enhancement was the most obvious. Commonly used perfusion indicators in CEUS, such as AT, time-to-peak and peak intensity, were obtained from the time-intensity curve. Percutaneous puncture biopsies were performed under ultrasound guidance, and specimens of all 50 lesions were examined pathologically. AT was significantly shorter in patients with pneumonia than in those with malignant tumors or chronic inflammation (p < 0.05), whereas no difference was seen between those with malignant tumors and those with chronic inflammation. No significant differences in time-to-peak or peak intensity were seen among those with various lung diseases (p > 0.05). This is the first description of a real-time comparative observation method using CEUS for determining the arterial phases in the lungs. This method is accurate, simple to perform and provides a direct display. It is expected to become a practical and feasible tool for diagnosing lung diseases.


Assuntos
Artérias Brônquicas/diagnóstico por imagem , Meios de Contraste/farmacocinética , Aumento da Imagem/métodos , Pneumopatias/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Ultrassonografia/métodos , Artérias Brônquicas/fisiologia , Feminino , Humanos , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiologia , Sensibilidade e Especificidade , Ultrassonografia Doppler em Cores
20.
Chin Med J (Engl) ; 129(3): 279-83, 2016 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-26831228

RESUMO

BACKGROUND: This study aimed to observe the differences in brain gray matter volume in drug-naive female patients after the first episode of major depression with and without stressful life events (SLEs) before the onset of depression. METHODS: Forty-three drug-naive female patients voluntarily participated in the present study after the first major depressive episode. The life event scale was used to evaluate the severity of the impact of SLEs during 6 months before the onset of the major depressive episode. High-field magnetic resonance imaging (MRI) scans were obtained, and the VBM and SPM8 software process were used to process and analyze the MRI. RESULTS: Compared to that in patients without SLEs, the volume of brain gray matter was lower in the bilateral temporal lobe, right occipital lobe, and right limbic lobe in the SLE group. However, the gray matter volume did not differ significantly between the two groups after the application of false discovery rate (FDR) correction. CONCLUSIONS: Although the results of the present study suggest the absence of significant differences in brain gray matter volume between female drug-naive patients after the first episode of major depression with and without SLEs after FDR correction, the study provides useful information for exploring the definitive role of stress in the onset of depression.


Assuntos
Depressão/fisiopatologia , Substância Cinzenta/anatomia & histologia , Estresse Fisiológico/fisiologia , Adolescente , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Software , Adulto Jovem
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