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1.
Eur Radiol ; 33(7): 4782-4788, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36645456

RESUMO

OBJECTIVES: We investigated the correlation of aponeurotic expansion of the supraspinatus tendon (AESST) with shoulder pathologies such as long head of biceps tendon (LHB), supraspinatus tendon (SST), and subscapularis tendon (SSc). METHODS: We retrospectively evaluated 47 healthy patients and 163 patients with shoulder symptoms from August 2014 to March 2021. First, the presence of AESST was evaluated based on Moser et al.'s classification. Second, the presence of abnormal findings of including LHB tendinitis, LHB subluxation, SST tendinitis, SST tear, SSc tendinitis, and SSc tendon tear was evaluated. We analyzed the prevalence and type of AESST between the two study groups and the relationship between abnormal findings and the presence of AESST. RESULTS: The prevalence of AESST for readers 1 and 2 was 26.1% and 30.4% in the asymptomatic group, respectively, and 22.8% and 31.3% in the symptomatic group. Type 1 was most common (17.3-23.9%) followed by types 2a and 2b. There were no significant differences in the distribution of aponeurosis type between the two groups. In the AESST-positive groups, 45.9% and 47.1% had SST tears on examination by readers 1 and 2, respectively, whereas only 26.4% and 27.9% had SST tears in the AESST-negative group suggesting AESST is associated with SST tear. The odds ratio for SST tear in the presence of AESST was 2.370 and 2.294 (readers 1 and 2). CONCLUSIONS: There is an association between SST tears and the presence of AESST. KEY POINTS: • We evaluated the prevalence of aponeurotic expansion of the supraspinatus tendon (AESST) on MR imaging by type in both symptomatic and asymptomatic groups. • We investigated the correlation of AESST with shoulder pathologies such as biceps tendon and supraspinatus tendon tears. • There is an association between SST tears and the presence of AESST. • Radiologists should be aware of the risk of rotator cuff pathology if AESST is detected.


Assuntos
Lesões do Manguito Rotador , Tendinopatia , Traumatismos dos Tendões , Humanos , Manguito Rotador/patologia , Ombro , Traumatismos dos Tendões/diagnóstico por imagem , Traumatismos dos Tendões/epidemiologia , Estudos Retrospectivos , Aponeurose/patologia , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/epidemiologia , Tendões/patologia , Ruptura , Imageamento por Ressonância Magnética/métodos , Tendinopatia/complicações , Tendinopatia/diagnóstico por imagem , Tendinopatia/epidemiologia
2.
J Opt Soc Am A Opt Image Sci Vis ; 37(5): 768-779, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32400710

RESUMO

Recent research has demonstrated that effective fusion of multispectral images (visible and thermal images) enables robust pedestrian detection under various illumination conditions (e.g., daytime and nighttime). However, there are some open problems such as poor performance in small-sized pedestrian detection and high computational cost of multispectral information fusion. This paper proposes a multilayer fused deconvolutional single-shot detector that contains a two-stream convolutional module (TCM) and a multilayer fused deconvolutional module (MFDM). The TCM is used to extract convolutional features from multispectral input images. Then fusion blocks are incorporated into the MFDM to combine high-level features with rich semantic information and low-level features with detailed information to generate features with strong a representational power for small pedestrian instances. In addition, we fuse multispectral information at multiple deconvolutional layers in the MFDM via fusion blocks. This multilayer fusion strategy adaptively makes the most use of visible and thermal information. In addition, using fusion blocks for multilayer fusion can reduce the extra computational cost and redundant parameters. Empirical experiments show that the proposed approach achieves an 81.82% average precision (AP) on a new small-sized multispectral pedestrian dataset. The proposed method achieves the best performance on two well-known public multispectral datasets. On the KAIST multispectral pedestrian benchmark, for example, our method achieves a 97.36% AP and a 20 fps detection speed, which outperforms the state-of-the-art published method by 6.82% in AP and is three times faster in its detection speed.

3.
Entropy (Basel) ; 21(6)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33267284

RESUMO

In this paper, we present a new effective infrared (IR) and visible (VIS) image fusion method by using a deep neural network. In our method, a Siamese convolutional neural network (CNN) is applied to automatically generate a weight map which represents the saliency of each pixel for a pair of source images. A CNN plays a role in automatic encoding an image into a feature domain for classification. By applying the proposed method, the key problems in image fusion, which are the activity level measurement and fusion rule design, can be figured out in one shot. The fusion is carried out through the multi-scale image decomposition based on wavelet transform, and the reconstruction result is more perceptual to a human visual system. In addition, the visual qualitative effectiveness of the proposed fusion method is evaluated by comparing pedestrian detection results with other methods, by using the YOLOv3 object detector using a public benchmark dataset. The experimental results show that our proposed method showed competitive results in terms of both quantitative assessment and visual quality.

5.
Sensors (Basel) ; 18(11)2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30400629

RESUMO

In this paper, we propose a new Intelligent Traffic Sign Recognition (ITSR) system with illumination preprocessing capability. Our proposed Dark Area Sensitive Tone Mapping (DASTM) technique can enhance the illumination of only dark regions of an image with little impact on bright regions. We used this technique as a pre-processing module for our new traffic sign recognition system. We combined DASTM with a TS detector, an optimized version of YOLOv3 for the detection of three classes of traffic signs. We trained ITSR on a dataset of Korean traffic signs with prohibitory, mandatory, and danger classes. We achieved Mean Average Precision (MAP) value of 90.07% (previous best result was 86.61%) on challenging Korean Traffic Sign Detection (KTSD) dataset and 100% on German Traffic Sign Detection Benchmark (GTSDB). Result comparisons of ITSR with latest D-Patches, TS detector, and YOLOv3 show that our new ITSR significantly outperforms in recognition performance.

6.
J Comput Assist Tomogr ; 41(6): 926-930, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28481805

RESUMO

OBJECTIVE: Park system is a magnetic resonance imaging (MRI) grading system for cervical neural foraminal stenosis (CNFS) and consists of 4 grades (0-3) based on the foraminal shape of 45-degree T2-weighted oblique sagittal images. The objective of this study was to evaluate the interreader reliability of the Park system among radiologists, residents, and clinicians. This study also assessed the correlations between radiologic and clinical findings. MATERIAL AND METHODS: A total of 289 patients (men:women = 155:134, mean age = 50 years) who underwent oblique sagittal MRI of the cervical spine at our hospital were included. According to the MR grading system suggested by Park et al (Br J Radiol 2013;86:20120515), 2 radiologists, 2 trainees, and 2 clinicians measured CNFS grade at the most narrow point. A neurosurgeon assessed the associated clinical manifestations. κ statistics were used to analyze the interreader agreement among the radiologists and clinicians. The clinical correlations between grade and positive clinical manifestations were assessed with R using nonparametric correlation analysis (Spearman correlation). RESULTS: The overall interreader agreements between radiologists, between trainees, between clinicians, and between radiologists and clinicians were almost perfect (κ = 0.80-0.96). There were moderate correlations between grade and clinical manifestations in each group (R = 0.562-0.669). There were moderate to relatively high correlations between grade and neurologic manifestations based on cervical level (R = 0.570-0.715) (all P < 0.05). CONCLUSIONS: Regardless of reader experience, there was substantial to almost perfect interreader reliability with the Park system for CNFS based on oblique sagittal MRI.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Estenose Espinal/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença
7.
Arch Microbiol ; 196(9): 611-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24906570

RESUMO

In this study, on evaluating the physiological function and mechanism of putrescine, we found that putrescine supplementation (1 mM) increases transcription of the putrescine aminotransferase gene, ygjG. Putrescine-dependent expression was confirmed by measuring ß-galactosidase activity and with reverse transcription-polymerase chain reaction. To understand the role of putrescine in ygjG expression, we genetically characterized and found that a knockout mutation in an alternative sigma factor, rpoS, abolished putrescine-dependent ygjG-lacZ expression. In the rpoS mutant, RpoS overexpression complemented the mutant phenotype. However, RpoS overexpression induced ygjG-lacZ expression with putrescine supplementation but not without supplementation. We also found that the loss of putrescine-dependent ygjG-lacZ expression induced by rpoS was completely restored under nitrogen-starvation conditions. The putrescine-dependent expression of ygjG-lacZ under this condition was clearly dependent on another alternative sigma factor, rpoN, and its cognate activator ntrC. These results show that rpoS is required for putrescine-dependent ygjG-lacZ expression, but the effect of putrescine on this expression is not caused by simple modulation of RpoS synthesis. Putrescine-dependent expression of ygjG-lacZ was controlled by at least two sigma factors: rpoS under excess nitrogen conditions and rpoN under nitrogen-starvation conditions. These results suggest that putrescine plays an important role in the nitrogen regulation system.


Assuntos
Proteínas de Escherichia coli/genética , Escherichia coli/enzimologia , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/genética , Transaminases/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Mutação , Nitrogênio/metabolismo , Putrescina/farmacologia , RNA Polimerase Sigma 54/metabolismo , Fator sigma/genética , Fator sigma/metabolismo
8.
Adv Biol Regul ; 89: 100975, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37302177

RESUMO

The 5' untranslated regions (UTRs) in messenger RNAs (mRNAs) play an important role in the regulation of protein synthesis. We had previously identified a group of mRNAs that includes human semaphorin 7A (SEMA7A) whose translation is upregulated by the Erk/p90S6K pathway in human eosinophils, with a potential negative impact in asthma and airway inflammation. In the current study, we aimed to find a common 5'UTR regulatory cis-element, and determine its impact on protein synthesis. We identified a common and conserved 5'UTR motif GGCTG-[(C/G)T(C/G)]n-GCC that was present in this group of mRNAs. Mutations of the first two GG bases in this motif in SEMA7A 5'UTR led to a complete loss of S6K activity dependence for maximal translation. In conclusion, the newly identified 5'UTR motif present in SEMA7A has a critical role in regulating S6K-dependent protein synthesis.


Assuntos
Biossíntese de Proteínas , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regiões 5' não Traduzidas , Proteínas Quinases S6 Ribossômicas/genética , Proteínas Quinases S6 Ribossômicas/metabolismo , Mutação
9.
Eur J Radiol ; 167: 111028, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37595398

RESUMO

PURPOSE: The aim of this study was to evaluate the relationship between the grade of signal change of the pericruciate fat pad (PCFP) and the location and severity of cartilage alterations in the knee on magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective study included 234 patients (M:F = 96:138, mean: 51 years) who underwent knee MRI. Two experienced musculoskeletal radiologists assessed any PCFP alterations (as grades 0-3) and chondral lesions using the modified Outerbridge grade (as grades 0-4). Bone marrow lesions (BMLs), meniscal status, anterior cruciate ligament alterations, and effusion-synovitis were also evaluated on the MRI. The relationships between PCFP alteration and MR findings (including the grade of chondral lesion) were evaluated. RESULTS: Signal changes in the PCFP were detected in 150 cases by Reader 1 (grade 0, 67 cases; grade 1, 53 cases; grade 2, 21 cases; grade 3, 9 cases) and in 154 cases by Reader 2 (grade 0, 59 cases; grade 1, 61 cases; grade 2, 24 cases; grade 3, 10 cases). The grade of PCFP signal change was statistically significantly correlated with the grade of the chondral lesion of the medial femoral condyle (MFC) (p = 0.029 and p = 0.003, respectively) and the medial tibial plateau (MTP) (p = 0.045, p = 0.002, Readers 1 and 2, respectively). The grade of PCFP signal change was significantly correlated with the grade of the BMLs of the MFC, MTP, and lateral femoral condyle (p < 0.05) for both readers. PCFP alteration was related to effusion-synovitis and tears of the medial meniscus. CONCLUSIONS: The grade of PCFP signal change was correlated with the severity of the cartilage alteration in the medial compartment of the knee joint and was also correlated with BMLs in the medial compartment, medial meniscal tears, and synovitis. Therefore, signal change in the PFCP seen on MRI can be an additional clue of the presence of osteoarthritis in the knee, particularly in the medial compartment.


Assuntos
Lesões do Ligamento Cruzado Anterior , Doenças Ósseas , Doenças das Cartilagens , Cartilagem Articular , Sinovite , Humanos , Estudos Retrospectivos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Meniscos Tibiais/patologia , Ligamento Cruzado Anterior , Imageamento por Ressonância Magnética , Doenças das Cartilagens/diagnóstico por imagem , Doenças das Cartilagens/patologia , Doenças Ósseas/patologia , Sinovite/patologia , Lesões do Ligamento Cruzado Anterior/patologia , Cartilagem Articular/diagnóstico por imagem
10.
Acta Neurochir (Wien) ; 154(2): 341-8; discussion 348, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21842210

RESUMO

BACKGROUND: To investigate characteristic clinical and radiological features of extradural arachnoid cysts (EDACs) in the thoracolumbar region, a retrospective review of medical records and imaging studies was performed. EDACs are well known but relatively rare lesions in the thoracolumbar spinal canal. The most common site is the lower thoracic spine, and it may cause neurological symptoms by compressing the spinal cord or nerve root. In this study, the pathogenesis, symptomatology, diagnostic approach, and surgical management of EDACs will be discussed. METHODS: We studied 14 consecutive patients who were surgically treated for EDACs in the thoracolumbar region at our institute between March 2000 and January 2011. The history, clinical presentations, image findings, operative findings, and surgical outcomes of these patients were retrospectively analyzed. The mean follow-up period was 28 months (range: 6-72 months). RESULTS: Progressive motor weakness was the predominant symptom in all patients. Nine patients had radicular leg pain and back pain in the thoracolumbar area. On MRI, the cyst compressed the dural sac and spinal cord posteriorly typically with bilateral foraminal extensions. On radiological study, a communication point with the subarachnoid was hardly observed. The surgical treatment of EDACs included complete resection of the walls and closing the communicating point with the subarachnoid space. All patients showed excellent outcomes according to Odom's criteria without recurrence. One CSF leakage and one postoperative hematoma were noted. CONCLUSIONS: Thoracolumbar EDAC patients presented paraparesis and leg pain. Complete excision and closing the communicating point with the subarachnoid space were the choices of treatment, and the outcomes were favorable.


Assuntos
Cistos Aracnóideos/diagnóstico , Cistos Aracnóideos/cirurgia , Vértebras Lombares/diagnóstico por imagem , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Laminectomia , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
11.
Ultrasonography ; 41(4): 698-705, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36195316

RESUMO

PURPOSE: This study evaluated epidermal cyst elasticity using multiple parameters of strain elastography (SE) and shear wave elastography (SWE) and assessed the reproducibility of each parameter. METHODS: This retrospective study included 73 patients with epidermal cysts who underwent SE and SWE. SE scores were classified as 1-4 according to elasticity. The strain ratio was evaluated using the elasticity ratio of lesions and adjacent subcutaneous fat tissue. For SWE, the shear wave velocity (m/s), elasticity (kPa) according to the Young modulus, velocity ratio, and elasticity ratio were evaluated. All values were measured twice. The reproducibility of SE and SWE measurements was assessed. The relationships among SE and SWE measurements were evaluated. RESULTS: The strain ratio on SE images showed good reproducibility (intra-class correlation coefficient [ICC]=0.789), and SE scores showed substantial reproducibility (kappa=0.753 and kappa=0.758 for readers 1 and 2, respectively). Moderate reproducibility was found for shear wave velocity and elasticity (ICC=0.750 and ICC=0.648, respectively), as well as for the shear wave velocity of the reference tissue and velocity ratio (ICC=0.747 and ICC=0.713, respectively). All SE scores were positively correlated with the strain ratio (P<0.001). The strain ratio in the second SE session was significantly correlated with the elasticity ratio and velocity ratio in the first SWE session (r=0.245, P=0.037; r=0.243, P=0.038, respectively). Other variables were not correlated. CONCLUSION: SE and SWE parameters of epidermal cysts showed moderate to good reproducibility. The strain ratio on SE showed good reproducibility and could provide relatively objective and consistent measurements of epidermal cyst elasticity.

12.
Acta Neurochir (Wien) ; 153(8): 1677-84; discussion 1685, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21720938

RESUMO

BACKGROUND: Cavernous malformations (CMs) are not uncommon, but most of them are found to be located intracranially. Intramedullary CMs are rare, accounting for only 3-5% of identified total central nervous system lesions. The natural history of intramedullary CMs and their clinical features, including the risk of hemorrhage from a large series, still remains unclear and needs to be elucidated. We review our experience with surgically treated patients with intramedullary CMs and discuss the clinical features and surgical outcomes. METHODS: Between March 2004 and March 2010, a total of 21 patients with intramedullary spinal cord CMs were surgically treated in a single institution. Data from 21 patients were retrospectively analyzed. RESULTS: There were 13 females and 8 males ranging in age from 10 to 70 years (mean age 39.3 years). All patients harbored single symptomatic CM of the nervous system, and multiple lesions were not found. The annual retrospective hemorrhage rate was 2.18% per patient/year. All but one CM were completely resected, and the average follow-up period was 22.1 months (1-73 months). Ten of the 21 patients experienced an improvement in neurological state, 9 patients remained unchanged, and 2 patients experienced worsening of their conditions. CONCLUSIONS: Symptomatic intramedullary CMs should be surgically removed to avoid further neurological deterioration. Though there are some limitations due to the retrospective nature of this study and its small number of patients, the prognosis was found to be related to the preoperative neurological state and to the type of symptom presentation.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Doenças Vasculares da Medula Espinal/patologia , Doenças Vasculares da Medula Espinal/cirurgia , Medula Espinal/cirurgia , Adolescente , Adulto , Idoso , Criança , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medula Espinal/irrigação sanguínea , Medula Espinal/patologia , Doenças Vasculares da Medula Espinal/fisiopatologia , Resultado do Tratamento , Adulto Jovem
13.
J Hosp Palliat Nurs ; 23(6): 584-590, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34587619

RESUMO

Few studies have examined why some hospitals operate independent hospice units (IHUs) and others do not. This study aims to investigate the organizational factors of hospitals having IHU. The units of analysis were individual hospitals. The study had a cross-sectional design and used health insurance claims data of 349 hospitals in Korea from January 1 to December 31, 2019. The dependent variable was whether a hospital operated an IHU. The independent variables were the percentage of patients with cancer, overall severity of patients, percentage of patients 60 years and older, health care cost per patient, percentage of inpatients, and nurse staffing level. Independent hospice units were present at 21.2% of the hospitals (74/349). The odds of having an IHU were significantly associated with the following factors: the percentage of patients with cancer (odds ratio [OR], 1.228; 95% confidence interval [CI], 1.071-1.408; P = .003), disease severity (OR, 5.129; 95% CI, 2.477-10.622; P < .001), percentage of patients 60 years and older (OR, 1.053; 95% CI, 1.015-1.092; P = .006), health care cost per patient (OR, 1.018; 95% CI, 1.009-1.027; P < .001), and nurse staffing level (OR, 0.439; 95% CI, 0.292-0.661; P < .001). The organizational factors of hospitals operating IHUs were similar to those of hospice facilities.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Hospitais para Doentes Terminais , Recursos Humanos de Enfermagem Hospitalar , Estudos Transversais , Humanos , República da Coreia
14.
Nucleic Acids Res ; 36(16): e103, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18644841

RESUMO

Protein transduction (PT) is a method for delivering proteins into mammalian cells. PT is accomplished by linking a small peptide tag--called a PT domain (PTD)--to a protein of interest, which generates a functional fusion protein that can penetrate efficiently into mammalian cells. In order to study the functions of a transcription factor (TF) of interest, expression plasmids that encode the TF often are transfected into mammalian cells. However, the efficiency of DNA transfection is highly variable among different cell types and is usually very low in primary cells, stem cells and tumor cells. Zinc-finger transcription factors (ZF-TFs) can be tailor-made to target almost any gene in the human genome. However, the extremely low efficiency of DNA transfection into cancer cells, both in vivo and in vitro, limits the utility of ZF-TFs. Here, we report on an artificial ZF-TF that has been fused to a well-characterized PTD from the human immunodeficiency virus-1 (HIV-1) transcriptional activator protein, Tat. This ZF-TF targeted the endogenous promoter of the human VEGF-A gene. The PTD-attached ZF-TF was delivered efficiently into human cells in vitro. In addition, the VEGF-A-specific transcriptional repressor retarded the growth rate of tumor cells in a mouse xenograft experiment.


Assuntos
Regulação da Expressão Gênica , Fatores de Transcrição/genética , Dedos de Zinco , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos , Camundongos Nus , Neoplasias/patologia , Neoplasias/terapia , Transporte Proteico , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química
15.
Mol Ther ; 16(6): 1033-40, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18398429

RESUMO

Inhibition of tumor angiogenesis through modulation of vascular endothelial growth factor (VEGF) and its signaling pathway has been clinically validated as a viable therapeutic modality in the treatment of cancer. The use of artificial transcription factors based on Cys2-His2 zinc-finger proteins (ZFPs) targeting the VEGF promoter offers a novel strategy for modulating VEGF levels in tumors. In order to demonstrate the utility of VEGF-targeted ZFPs as therapeutic agents, we generated adenoviruses (Ads) expressing VEGF promoter-targeted transcriptional repressor ZFP, F435-KOX. A replication-incompetent Ad expressing F435-KO X, namely, Ad-DeltaE1-KOX, significantly reduced VEGF expression and functionally led to inhibition of angiogenesis. In vivo, an oncolytic Ad expressing F435-KOX, namely, Ad-DeltaB7-KOX, elicited a pronounced antitumor effect against a human glioblastoma xenograft model, U87MG. Further, consistent with its expected mechanism of action, Ad-DeltaB7-KOX was shown to greatly reduce the level of VEGF and vessel density in tumor tissue and increase terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic cells in tumors. Survival rates were also significantly increased in Ad-DeltaB7-KOX-treated mice. Taken together, the findings from this study identify F435-KOX as a novel and potent ZFP transcription factor that can inhibit VEGF-A-mediated angiogenesis and offer a novel therapeutic modality in the treatment of cancer.


Assuntos
Adenoviridae/genética , Inibidores da Angiogênese/farmacologia , Vírus Oncolíticos/genética , Fator A de Crescimento do Endotélio Vascular/genética , Dedos de Zinco , Animais , Apoptose , Endotélio Vascular/citologia , Glioblastoma/terapia , Humanos , Camundongos , Transplante de Neoplasias , Regiões Promotoras Genéticas , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Drug News Perspect ; 21(8): 417-23, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19034347

RESUMO

Proteases play important roles in the development and homeostasis of an organism. These versatile proteins participate in a variety of biological processes. In addition to these functions, the importance of proteases as a key player in cancer progression has been increasingly recognized. Proteolysis by dysregulated proteases is one of the hallmarks of cancer progression. In many cancers, a variety of functions have been uncovered for the type II transmembrane serine proteases (TTSPs), which are recently discovered members of the family of cell-surface associated proteases. In this review, we describe the characteristics of TTSPs and their role in many human cancers. Among the many TTSPs, we discuss TMPRSS4/MT-SP2 in the greatest detail. TMPRSS4 is upregulated in prostate, colon and gastric cancers, and was recently shown to promote tumor growth, invasion, metastasis and the epithelial-mesenchymal transition (EMT). Currently, efforts are being made to understand the pathways through which TMPRSS4 activates the EMT. Recent studies indicate that the EMT induced by TMPRSS4 involves activation of extracellular signal regulated kinase (ERK) 1/2 and mitogen-activated protein kinase (MAPK). The target molecule for TMPRSS4 that initiates the EMT stimulatory pathway is still not defined. Regulation of the EMT by proteases such as TMPRSS4 may provide novel therapeutic targets for a cancer metastasis inhibitor.


Assuntos
Biomarcadores Tumorais/biossíntese , Proteínas de Membrana/biossíntese , Neoplasias/patologia , Serina Endopeptidases/biossíntese , Biomarcadores Tumorais/genética , Progressão da Doença , Epitélio/metabolismo , Epitélio/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , Mesoderma/metabolismo , Mesoderma/patologia , Invasividade Neoplásica , Neoplasias/metabolismo , Serina Endopeptidases/genética , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Medicine (Baltimore) ; 97(35): e11919, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30170385

RESUMO

A number of studies have demonstrated an association of neuropathic pain and chronic low back pain (CLBP), but the outcome difference in each medical management is poorly understood. This study is aimed to investigate treatment patterns of neuropathic pain in CLBP patients and to explore patient-reported outcomes (PROs) including quality of life (QoL) and functional disability by treatment patterns.Data were extracted from the neuropathic low back pain (NLBP) outcomes research. It was a multicenter and cross-sectional study in which 1200 patients were enrolled at 27 general hospitals, from 2014 to 2015. Of total, 478 patients classified as neuropathic pain were used for this subgroup analysis. The patients were divided into 2 groups according to treatment patterns (with vs. without the targeted therapy [TT] of neuropathic pain). Demographic and clinical features were collected by chart reviews and PROs were measured by patient's survey. QoL was assessed by EuroQoL 5-dimension (EQ-5D) questionnaire. Functional disability was measured by the Quebec Back Pain Disability Scale (QBPDS). Multiple linear regression analyses were conducted to compare the PROs between TT group and non-targeted therapy (nTT) group.Among the NLBP patients (mean age 63years, female 62%), EQ-5D index, EuroQoL-Visual Analog Scale (EQ-VAS), and QBPDS Scores (mean ±â€Šstandard deviation) were 0.40 ±â€Š0.28, 54.98 ±â€Š19.98, and 46.03 ±â€Š21.24, respectively. Only 142 (29.7%) patients had pharmacological TT of neuropathic pain. Univariate analyses revealed no significant mean differences between TT group and nTT group in the EQ-5D index (0.41 ±â€Š0.27 and 0.39 ±â€Š0.28), EQ-VAS (56.43 ±â€Š18.17 and 54.37 ±â€Š20.69), and QBPDS (45.31 ±â€Š21.32 and 46.31 ±â€Š21.24). After adjustment with covariates, TT group had higher scores of EQ-5D index (ß = 0.07; P < 0.01) and EQ-VAS (ß = 4.59; P < 0.05) than the nTT group. The TT group's QBPDS score was lower than the nTT group, although its statistical significance still has not been reached (ß = -4.13; P = 0.07).We found that considerable proportion of the NLBP patients remains untreated or undertreated. Although TT group had significantly better QoL than nTT group, only 29.7% of NLBP patients had pharmacological TT. Therefore, clinicians should consider using TT for better QoL of neuropathic pain patients.


Assuntos
Analgésicos/uso terapêutico , Dor Crônica/tratamento farmacológico , Dor Lombar/tratamento farmacológico , Neuralgia/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Estudos Transversais , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , República da Coreia , Resultado do Tratamento
18.
Nat Biotechnol ; 21(3): 275-80, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12592413

RESUMO

We describe methods for generating artificial transcription factors capable of up- or downregulating the expression of genes whose promoter regions contain the target DNA sequences. To accomplish this, we screened zinc fingers derived from sequences in the human genome and isolated 56 zinc fingers with diverse DNA-binding specificities. We used these zinc fingers as modular building blocks in the construction of novel, sequence-specific DNA-binding proteins. Fusion of these zinc-finger proteins with either a transcriptional activation or repression domain yielded potent transcriptional activators or repressors, respectively. These results show that the human genome encodes zinc fingers with diverse DNA-binding specificities and that these domains can be used to design sequence-specific DNA-binding proteins and artificial transcription factors.


Assuntos
Regulação da Expressão Gênica , Biblioteca de Peptídeos , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Dedos de Zinco/genética , DNA/química , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Genoma Humano , Humanos , Engenharia de Proteínas/métodos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Fatores de Transcrição/química , Transcrição Gênica , Leveduras/genética , Leveduras/metabolismo
19.
Nucleic Acids Res ; 33(8): e74, 2005 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-15860771

RESUMO

Gene expression is regulated at the transcriptional and post-transcriptional levels. Therefore, in order to achieve a high level of silencing, which includes minimizing any residual expression of a target gene, suppression at both the transcriptional and post-transcriptional levels is required. In this study, we describe a new method for highly efficient gene silencing that combines zinc finger protein-mediated transcriptional repression and small interfering RNA (siRNA)-mediated inhibition of post-transcriptional events. To measure the amount of gene expression under various conditions, we used a luciferase reporter gene that was driven by a variety of promoters, including that of the human vascular endothelial growth factor-A (VEGF-A) gene. We also measured expression of the endogenous VEGF-A gene. Inhibition of gene expression by each of the two individual technologies was effective, but in-depth analyses revealed residual expression of the target gene. The combination of specific zinc finger transcription factors and siRNAs greatly enhanced the silencing of the human VEGF-A gene, not only when cells were grown in the presence of normal amounts of oxygen but also under conditions of hypoxic stimulation. These results suggest that a bi-level approach to the silencing of VEGF-A expression may be clinically beneficial as part of a cancer treatment protocol.


Assuntos
Inativação Gênica , Interferência de RNA , Fator A de Crescimento do Endotélio Vascular/genética , Hipóxia Celular , Linhagem Celular , Genes Reporter , Humanos , Regiões Promotoras Genéticas , RNA Interferente Pequeno/genética , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Dedos de Zinco
20.
J Korean Neurosurg Soc ; 60(4): 441-447, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28689393

RESUMO

OBJECTIVE: Computed tomography (CT)-based method of three dimensional (3D) analysis (MIMICS®, Materialise, Leuven, Belgium) is reported as very useful software for evaluation of OPLL, but its reliability and reproducibility are obscure. This study was conducted to evaluate the accuracy of MIMICS® system, and inter- and intra-observer reliability in the measurement of OPLL. METHODS: Three neurosurgeons independently analyzed the randomly selected 10 OPLL cases with medical image processing software (MIMICS®) which create 3D model with Digital Imaging and Communication in Medicine (DICOM) data from CT images after brief explanation was given to examiners before the image construction steps. To assess the reliability of inter- and intra-examiner intraclass correlation coefficient (ICC), 3 examiners measured 4 parameters (volume, length, width, and length) in 10 cases 2 times with 1-week interval. RESULTS: The inter-examiner ICCs among 3 examiners were 0.996 (95% confidence interval [CI], 0.987-0.999) for volume measurement, 0.973 (95% CI, 0.907-0.978) for thickness, 0.969 (95% CI, 0.895-0.993) for width, and 0.995 (95% CI, 0.983-0.999) for length. The intra-examiner ICCs were 0.994 (range, 0.991-0.996) for volume, 0.996 (range, 0.944-0.998) for length, 0.930 (range, 0.873-0.947) for width, and 0.987 (range, 0.985-0.995) for length. CONCLUSION: The medical image processing software (MIMICS®) provided detailed quantification OPLL volume with minimal error of inter- and intra-observer reliability in the measurement of OPLL.

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