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1.
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
2.
J Spinal Disord Tech ; 26(8): 415-20, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22367466

RESUMO

STUDY DESIGN: Retrospective study. OBJECTIVES: To compare the efficacy of 2-level anterior cervical discectomy and fusion with cage alone (ACDF-CA) and with cage and plate construct (ACDF-CPC) with regard to clinical outcome and radiologic changes. SUMMARY OF BACKGROUND DATA: The use of stand-alone cervical interbody cages in ACDF has become popular, but high subsidence rates have been reported in the literature. METHODS: A total of 54 consecutive patients who underwent 2-level ACDF-CA or ACDF-CPC after suffering from cervical radiculopathy were divided into 2 groups: group A (n = 28) underwent ACDF-CA, group B (n = 26) underwent ACDF-CPC. Fusion rate, global and segmental kyphosis, disk height, and subsidence rate were assessed by radiolographs. Clinical outcomes were assessed using Robinson's criteria. RESULTS: Solid fusion was achieved in 96.43% (27/28) in group A and in 96.15% (25/26) in group B. Fusion segmental kyphosis of >5 degrees occurred in 14.29% (4/28) of group A and in 7.69% (2/26) of group B; however, there was no statistical difference between the 2 groups (P>0.05). Subsidence occurred in 35.71% (10/28) of group A as compared with 11.54% (3/26) of group B (P<0.05). Clinical outcomes were similar in the 2 treatment groups. CONCLUSIONS: The use of cage and plate construct in 2-level ACDF results in a shorter fusion duration and a lower subsidence rate than that of cage alone; however, there is no significant difference in the postoperative global and segmental alignment and clinical outcomes between groups.


Assuntos
Placas Ósseas , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Fusão Vertebral/métodos , Adulto , Idoso , Placas Ósseas/efeitos adversos , Feminino , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/cirurgia , Cifose/diagnóstico por imagem , Cifose/cirurgia , Lordose/diagnóstico por imagem , Lordose/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
3.
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
4.
Biology (Basel) ; 12(6)2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37372111

RESUMO

This study was carried out to clarify the spatial distribution of exotic plants at national, regional, and local levels, as well as their ecological impacts, and to prepare a strategy to reduce the impacts in Republic of Korea. This study was attempted at the national, regional, and local levels throughout Republic of Korea. Compositae occupied the highest percentage among invading exotic plants in Republic of Korea. A review of the biological attributes of exotic plants based on the dormancy form, longevity, disseminule form, growth form, and radicoid form showed that therophytes, annual plants, plants that disperse seeds by gravity (D4), erect form (E), and nonclonal growth form (R5) occupied the highest proportion. At the national level, the spatial distribution of exotic plants tended to depend on topographic conditions such as elevation and slope degree, and to increase around urbanized areas, agricultural fields, and coastal areas. The habitat types that exotic plants established were similar in their native habitat and in Korea, where they invaded. They preferred disturbed land such as roadsides, bare ground, agricultural fields, and so on. The spatial distribution of vegetation types dominated by exotic plants was restricted in the lowland. The proportion of the exotic/native plants tended to proportionate reversely to the vegetation type richness (the number of vegetation types); that is, the ecological diversity. The proportion of the exotic plants was higher in artificial plantations, vegetation due to disturbance, and vegetation established on lower slopes compared with upper slopes. Even at the local level, the exotic plants appeared abundantly in the introduced vegetation, while they were rare in the native ones. In the vegetation infected by exotic species, not only the species composition changed significantly, but the species diversity also decreased. Restorative treatment by introducing mantle vegetation around the hiking trail inhibited the establishment of exotic plants. Further, the restoration practice recovered the similarity of the species composition compared to the reference vegetation and increased the species diversity.

5.
J Clin Neurosci ; 94: 271-280, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34863450

RESUMO

Laminectomy with instrumented fusion (LF) has demonstrated better prevention of ossification of posterior longitudinal ligament (OPLL) growth compared to laminoplasty (LP). There remains uncertainty, however, as to which surgical approach is more beneficial with respect to clinical outcomes and complications. We retrospectively reviewed 273 cervical OPLL patients of more than 3 levels, from the two institutions' databases, who underwent LF or LP between January 1998 and January 2016. Each 273 patient (85 with LF, 188 with LP) was assessed for postoperative neurologic and radiologic outcomes, complications and reoperations. The mean length of follow-up was 40.11 months. There were baseline differences between cohorts. Overall, postoperative JOA recovery rate at last follow up was significantly better in the LP group with similar improvement in visual analog neck score. Postoperative C2-7 Cobb angle was decreased compared to baseline for both LF and LP cohorts, but there was no significant difference between groups. Complications occurred in 19 (22.35%) LF patients, and 11 (5.85%) LP patients, with higher incidence of C5 palsy and instrumentation failure in the LF group. Four LF patients (4.71%) and five LP patients (2.66%) underwent reoperation during the follow up period.


Assuntos
Laminoplastia , Fusão Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Humanos , Laminectomia , Ligamentos Longitudinais , Osteogênese , Estudos Retrospectivos , Resultado do Tratamento
6.
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
7.
Quant Imaging Med Surg ; 10(11): 2112-2124, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33139991

RESUMO

BACKGROUND: Cervical spondylotic myelopathy (CSM) is one of the most common causes of spinal cord impairment in elderly patients. However, a consensus has yet to be reached on the ideal method of surgical intervention. In this study, we investigated serial changes of radiological findings after three-level anterior cervical discectomy and fusion (ACDF) and multilevel laminoplasty and attempted to identify the radiological parameters affecting long-term clinical outcomes in CSM. METHODS: Of the 152 patients with multilevel CSM treated with three-level ACDF and multilevel laminoplasty, 42 had complete radiological parameters both before and 2 years after surgery (three-level ACDF, 22 patients; multilevel laminoplasty, 20 patients). Radiological parameters included spinal cord signal intensity (SI) changes on magnetic resonance imaging (MRI). Clinical outcomes including the Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), Oswestry disability index (ODI), and 36-Item Short Form Health Survey score were measured. RESULTS: The ACDF group showed significant restoration of segmental lordosis postoperatively (preoperatively: 2.21°, 6 months: 8.37°, P=0.026), and segmental and cervical range of motion (ROM) was markedly reduced and well maintained until the final follow-up (preoperatively: 25.48°, 24 months: 4.35°, P<0.001; preoperatively: 41.71°, 24 months: 20.18°, P<0.001). The recovery rates of the JOA score were 42.85% and 57.40% in the ACDF and laminoplasty groups, respectively, although this difference was not statistically significant. Multivariate regression analysis demonstrated that signal change on MRI significantly affected the recovery rate (P=0.003). The visual analog scale (VAS) score and NDI decreased considerably only in the laminoplasty group, and device complications were confirmed only in the ACDF group (incidence rate =36.5%). CONCLUSIONS: Multilevel laminoplasty showed better radiological and similar clinical outcomes. ACDF had more surgical complications. Spinal cord SI change on preoperative MRI was the independent risk factor for poor clinical outcomes. We recommend laminoplasty instead of three-level ACDF to treat multilevel CSM.

8.
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
9.
World Neurosurg ; 126: e196-e207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30797909

RESUMO

OBJECTIVE: There is a paucity of studies on readmission rates in elderly patients over a period of 360 days after spinal surgery. METHODS: We identified 1248 patients older than 70 years who underwent degenerative lumbar spinal surgery from November 2005 to April 2015. We reviewed the patients who were readmitted within 360 days and compared them by univariate and multivariate analysis with the nonreadmitted patients for each period of 0-30, 30-90, 90-180, and 180-360 days postoperatively to determine risk factors for hospital readmission. RESULTS: A total of 1248 patients (733 female, 58.7%) were enrolled in the study. The number of readmitted patients was 37 (2.96%), 94 (7.53%), 145 (11.62%), 182 (14.58%), and 213 (17.07%) at 30, 90, 180, 270, and 360 days, respectively. Surgical site-related problems decreased gradually in the first 0-90 days and slightly increased after then. Non-surgical site-related problems gradually increased with time. Logistic multiple regression analysis showed that electrocardiographic abnormalities, male sex, low hemoglobin levels, asthma, heart disease, intensive care unit admission, low alanine aminotransferase level, high body mass index, and high platelet level were risk factors for readmission. CONCLUSIONS: We found that electrocardiographic abnormalities, male sex, low hemoglobin levels, asthma, heart disease, intensive care unit admission, low aspartate aminotransferase level, high body mass index, and high platelet level were risk factors for readmission. As the postoperative observational period became longer, the reasons for readmission tended to be more related to non-surgical site-related problems than to surgical-related problems.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Aspartato Aminotransferases/sangue , Asma/complicações , Índice de Massa Corporal , Cuidados Críticos/estatística & dados numéricos , Eletrocardiografia , Feminino , Cardiopatias/complicações , Humanos , Masculino , Contagem de Plaquetas , Complicações Pós-Operatórias , Fatores de Risco , Fatores Sexuais , Fusão Vertebral
10.
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
11.
Spine J ; 18(10): 1779-1786, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29526640

RESUMO

BACKGROUND CONTEXT: Despite the fact that ossification of posterior longitudinal ligament (OPLL) is a three-dimensional disease, conventional studies have focused mainly on a two-dimensional measurement, and it is difficult to accurately determine the volume of OPLL growth and analyze the factors affecting OPLL growth after posterior decompression (laminoplasty or laminectomy and fusion). PURPOSE: The present study aimed to investigate the factors affecting OPLL volume growth using a three-dimensional measurement. STUDY DESIGN/SETTING: This was a retrospective case study. PATIENT SAMPLE: Eighty-three patients with cervical OPLL who were diagnosed as having multilevel cervical OPLL of more than three levels on cervical computed tomography (CT) scans were retrospectively reviewed from June 1, 1998, to December 31, 2015. OUTCOME MEASURES: The OPLL volume from the C1 vertebrae to the C7 vertebrae was measured on preoperative and the most recent follow-up CT scans. METHODS: Eighty-three patients were retrospectively examined for age, gender, body mass index, hypertension, diabetes, type of OPLL, surgical method, preoperative cervical curvature, and preoperative and postoperative cervical range of motion. Preoperative cervical CT and the most recent follow-up cervical CT scans were converted to Digital Imaging and Communications in Medicine data, and the OPLL volume was three-dimensionally measured using the Mimics program (Materialise, Leuven, Belgium). The OPLL volume growth was analyzed using univariate and multivariate analyses. RESULTS: The average follow-up period was 32.36 (±23.39) months. Patients' mean age was 54.92 (±8.21) years. In univariate analysis, younger age (p=.037) and laminoplasty (p=.012) were significantly associated with a higher mean annual growth rate of OPLL (%/y). In multivariate analysis, only laminoplasty (p=.027) was significantly associated with a higher mean annual growth rate of OPLL (%/y). The mean annual growth rate of OPLL was about seven times faster with laminoplasty (8.00±13.06%/y) than with laminectomy and fusion (1.16±9.23%/y). CONCLUSIONS: Posterior instrumented fusion has the effect of reducing OPLL growth rate compared with motion-preserving laminoplasty. Patients' age and the surgical method need to be considered in surgically managing the multilevel OPLL.


Assuntos
Vértebras Cervicais/patologia , Imageamento Tridimensional/métodos , Ossificação do Ligamento Longitudinal Posterior/etiologia , Fusão Vertebral/métodos , Adulto , Idoso , Vértebras Cervicais/diagnóstico por imagem , Feminino , Humanos , Laminectomia/efeitos adversos , Laminectomia/métodos , Laminoplastia/efeitos adversos , Laminoplastia/métodos , Ligamentos Longitudinais/diagnóstico por imagem , Ligamentos Longitudinais/patologia , Masculino , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Amplitude de Movimento Articular , Análise de Regressão , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
12.
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
13.
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
14.
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
15.
Yonsei Med J ; 48(3): 440-8, 2007 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-17594152

RESUMO

PURPOSE: We performed 65 cases of posterior fusion surgery for cervical and/or high thoracic lesions using a polyaxial screw-rod system. PATIENTS AND METHODS: A total of 486 screws were implanted in 65 patients. RESULTS: Fixation of the screws was carried out over an average of 2.9 spinal segments. Upon evaluation by postoperative CT scans, twelve (2.5%) screws had suboptimal trajectories but two of these revealed radiculopathy in one patient and required screw repositioning. No vascular sequelae resulted. There has been no segmental motion in any of the cases to date. As for other complications, there was one case of dural tearing and two cases of lateral mass fractures. There were no infections or other wound healing problems or hardware failures. No patients had neurological deterioration after surgery. There were statistically significant improvements in the mean Neck Disability Index (NDI) scores and Visual Analogue Scale (VAS) scores in the preoperative and late postoperative follow-up evaluations. Although further studies are required to establish the long-term results of fusion rates and clinical outcomes. CONCLUSION: We cautiously suggest that the posterior polyaxial screw-rod system can be safely used as a primary or additional fusion method in this risky region. The successful and safe use of this method is dependent on a precise preoperative surgical plan and tactics for ensuring safe screw fixation.


Assuntos
Parafusos Ósseos , Vértebras Cervicais/cirurgia , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Doenças da Coluna Vertebral/fisiopatologia , Fusão Vertebral/instrumentação , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
Yonsei Med J ; 48(3): 457-64, 2007 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-17594154

RESUMO

PURPOSE: We have experienced 23 patients who had underwent cervical disc replacement with Mobi-C disc prosthesis and analyzed their radiological results to evaluate its efficacy. PATIENTS AND METHODS: This study was performed on 23 patients with degenerative cervical disc disease who underwent CDR with Mobi-C disc prosthesis from March 2006 to June 2006. RESULTS: The age of the study population ranged from 31 to 62 years with mean of 43 years, and 16 male and 7 female cases. Regarding axial pain, the average preoperative VAS score was 6.47 +/- 1.4, while at final follow-up it was 1.4 +/- 0.7 (p < 0.001). The preoperatively VAS score for radiculopathy was 6.7 +/- 0.7 compared with an average score of 0 +/- 0 at the final follow-up (p < 0.001). At postoperative 6th month, Odom's criteria were excellent, good, or fair for all 23 patients (100%). 7 patients (30.4%) were classified as excellent, 15 patients (65.2%) as good, and 1 patients (4.4%) as fair. Prolo economic and functional rating scale was average 8.9 +/- 0.7 at postoperative 6th month. ROM in C2-7, ROM of FSU, and ROM in upper adjacent level were well preserved after CDR. CONCLUSION: This report would be the first document about the CDR with Mobi-C disc prosthesis in the treatment of degenerative cervical disc disease. CDR with Mobi-C disc prosthesis provided a favorable clinical and radiological outcome in this study. However, Long-term follow-up studies are required to prove its efficacy and ability to prevent adjacent segment disease.


Assuntos
Vértebras Cervicais/cirurgia , Discotomia/métodos , Adulto , Vértebras Cervicais/fisiopatologia , Discotomia/efeitos adversos , Discotomia/instrumentação , Feminino , Humanos , Prótese Articular/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Amplitude de Movimento Articular , Fatores de Tempo , Resultado do Tratamento
17.
Asian Spine J ; 11(6): 917-927, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29279747

RESUMO

STUDY DESIGN: A noninterventional, multicenter, cross-sectional study. PURPOSE: We investigated the prevalence of neuropathic pain (NP) and patient-reported outcomes (PROs) of the quality of life (QoL) and functional disability in Korean adults with chronic low back pain (CLBP). OVERVIEW OF LITERATURE: Among patients with CLBP, 20%-55% had NP. METHODS: Patients older than 20 years with CLBP lasting for longer than three months, with a visual analog scale (VAS) pain score higher than four, and with pain medications being used for at least four weeks before enrollment were recruited from 27 general hospitals between December 2014 and May 2015. Medical chart reviews were performed to collect demographic/clinical features and diagnosis of NP (douleur neuropathique 4, DN4). The QoL (EuroQoL 5-dimension, EQ-5D; EQ-VAS) and functional disability (Quebec Back Pain Disability Scale, QBPDS) were determined through patient surveys. Multiple linear regression analyses were performed to compare PROs between the NP (DN4≥4) and non-NP (DN4<4) groups. RESULTS: A total of 1,200 patients (females: 65.7%; mean age: 63.4±13.0 years) were enrolled. The mean scores of EQ-5D, EQ-VAS, and QBPDS were 0.5±0.3, 55.7±19.4, and 40.4±21.1, respectively. Among all patients, 492 (41.0%; 95% confidence interval, 38.2%-43.8%) suffered from NP. The prevalence of NP was higher in male patients (46.8%; p<0.01), in patients who had pain based on radiological and neurological findings (59.0%; p<0.01), and in patients who had severe pain (49.0%; p<0.01). There were significant mean differences in EQ-5D (NP group vs. non-NP group: 0.4±0.3 vs. 0.5±0.3; p<0.01) and QBPDS (NP group vs. non-NP group: 45.8±21.2 vs. 36.3±20.2; p<0.01) scores. In the multiple linear regression, patients with NP showed lower EQ-5D (ß=-0.1; p<0.01) and higher QBPDS (ß=7.0; p<0.01) scores than those without NP. CONCLUSIONS: NP was highly prevalent in Korean patients with CLBP. Patients with CLBP having NP had a lower QoL and more severe dysfunction than those without NP. To enhance the QoL and functional status of patients with CLBP, this study highlights the importance of appropriately diagnosing and treating NP.

18.
J Neurosurg ; 104(1 Suppl): 37-40, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16509479

RESUMO

Spondylocostal dysostosis is a rare congenital segmental costovertebral malformation. Neural tube defects associated with it have been reported several times, and a genetic cause has been proposed. The authors report on the first patient with both spondylocostal dysostosis and an intrathoracic myelomeningocele in whom surgical treatment was successful.


Assuntos
Disostoses/complicações , Meningomielocele/etiologia , Meningomielocele/cirurgia , Vértebras Torácicas/anormalidades , Humanos , Lactente , Masculino , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento
19.
Yonsei Med J ; 47(3): 319-25, 2006 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-16807980

RESUMO

This study sought to determine the outcomes of posterior lumbar interbody fusion (PLIF), via a unilateral approach, in selected patients who presented with unilateral leg pain and segmental instability of the lumbar spine. Patients with a single level of a herniated disc disease in the lumbar spine, unilateral leg pain, chronic disabling lower back pain (LBP), and a failed conservative treatment, were considered for the procedure. A total of 41 patients underwent a single-level PLIF using two PEEK (Poly-Ether-Ether-Ketone) cages filled with iliac bone, via a unilateral approach. The patients comprised 21 women and 20 men with a mean age of 41 years (range: 22 to 63 years). Two cages were inserted using a unilateral medial facetectomy and a partial hemilaminectomy. At follow-up, the outcomes were assessed using the Prolo Scale. The success of the fusion was determined by dynamic lumbar radiography and/or computerized tomography scanning. All the patients safely underwent surgery without severe complications. During a mean follow-up period of 26 months, 1 patient underwent percutaneous pedicle screw fixation due to persistent LBP. A posterior displacement of the cage was found in one patient. At the last follow up, 90% of the patients demonstrated satisfactory results. An osseous fusion was present in 85% of the patients. A PLIF, via a unilateral approach, enables a solid union with satisfactory clinical results. This preserves part of the posterior elements of the lumbar spine in selected patients with single level instability and unilateral leg pain.


Assuntos
Deslocamento do Disco Intervertebral/cirurgia , Instabilidade Articular/cirurgia , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Adulto , Feminino , Seguimentos , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Instabilidade Articular/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Resultado do Tratamento
20.
Yonsei Med J ; 47(3): 326-32, 2006 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-16807981

RESUMO

We report a series of epidural hematomas which cause neurologic deterioration after spinal surgery, and have taken risk factors and prognostic factors into consideration. We retrospectively reviewed the database of 3720 cases of spine operation in a single institute over 7 years (1998 April- 2005 July). Nine patients who demonstrated neurologic deterioration after surgery and required surgical decompression were identified. Factors postulated to increase the postoperative epidural hematoma and to improve neurologic outcome were investigated. The incidence of postoperative epidural hematoma was 0.24%. Operation sites were cervical 3 cases, thoracic 2 cases, and lumbar 4 cases. Their original diagnoses were tumor 3 cases, cervical stenosis 2 cases, lumbar stenosis 3 cases and herniated lumbar disc 1 case. The symptoms of epidural hematomas were neurologic deterioration and pain. After decompression, clinical outcome revealed complete recovery in 3 cases (33.3%), incomplete recovery in 5 cases (55.6%) and no change in 1 case (11.1%). Factors increasing the risk of postoperative epidural hematoma were coagulopathy from medical illness or anticoagulation therapy (4 cases, 44.4%) and highly vascularized tumor (3 cases, 33.3%). The time interval to evacuation of complete recovery group (29.3 hours) was shorter than incomplete recovery group (66.3 hours). Patients with coagulopathy and highly vascularized tumor were more vulnerable to spinal epidural hematoma. The postoperative outcome was related to the preoperative neurological deficit and the time interval to the decompression.


Assuntos
Hematoma Epidural Espinal/epidemiologia , Hematoma Epidural Espinal/etiologia , Complicações Pós-Operatórias/epidemiologia , Doenças da Coluna Vertebral/cirurgia , Adulto , Idoso , Feminino , Hematoma Epidural Espinal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
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