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OBJECTIVES: The relationships between calcaneal bone mass and dietary/lifestyle habits in women at 3-4 months postpartum were examined in the context of osteoporosis prevention. STUDY DESIGN: Cross-sectional survey. METHODS: We measured bone mass using calcaneal ultrasound in mothers who brought their 3- to 4-month-old babies to healthcare centers in Japan for health examination and administered a self-report questionnaire on physical characteristics and dietary/lifestyle habits to those who agreed to participate in the survey. Valid data were available for 1220 women (valid response rate, 97.5%). RESULTS: Based on their stiffness score, a measure of bone mass, 70.9% (n = 865) of the participants were classified as 'no apparent abnormality (stiffness score ≥78.8)' (low-risk group), 18.2% (n = 222) as 'guidance required (≥70.1-<78.8)' (intermediate-risk group), and 10.9% (n = 133) as 'complete examination required (<70.1)' (high-risk group), according to the criteria for osteoporosis screening test results. The percentage of individuals with a history of fracture was higher in the guidance required/complete examination required than in the no apparent abnormality group (P = 0.016). The analysis of relationships between the consumption frequency of certain foods, such as calcium-rich foodstuffs, and bone mass found that women who reported lower frequencies of milk and dark-colored (beta-carotene rich) vegetables for breakfast consumption had a significantly lower bone mass than those who consumed these foods more often. Furthermore, the guidance required/complete examination required group had a significantly lower calcium intake than the no apparent abnormality group (P = 0.022). CONCLUSIONS: These results indicate the need to provide postpartum women with dietary education programs to promote healthy eating habits, such as increased consumption of calcium-rich foods, and prevent osteoporosis.
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Densidad Ósea , Conducta Alimentaria , Hábitos , Estilo de Vida , Periodo Posparto/psicología , Adulto , Estudios Transversales , Femenino , Humanos , Japón , Osteoporosis/prevención & control , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Residual sleepiness after continuous positive airway pressure (CPAP) is a critical problem in some patients with obstructive sleep apnea syndrome (OSAS). However, nasal surgery is likely to reduce daytime sleepiness and feelings of unrefreshed sleep. The aim of this study is to clarify the effects of nasal surgery and CPAP on daytime sleepiness. METHODOLOGY: This is a retrospective and matched-case control study. The participants were consecutive 40 patients with OSAS who underwent nasal surgery (Surgery group) and 40 matched patients who were treated with CPAP (CPAP group). RESULTS: In the Surgery group, although the nasal surgery did not decrease either apnea or hypopnea, it improved oxygenation, the quality of sleep. In the CPAP Group, the CPAP treatment reduced apnea and hypopnea, and improved oxygenation, quality of sleep. The degree of relief from daytime sleepiness was different between the two groups. The improvement of Epworth Sleepiness Scale was more significant in the Surgery Group than those in the CPAP Group (Surgery from 11.0 to 5.1, CPAP from 10.0 to 6.2). DISCUSSION: These findings suggest that the results of the nasal surgery is more satisfactory for some patients with OSAS than CPAP on daytime sleepiness.
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Presión de las Vías Aéreas Positiva Contínua/métodos , Polisomnografía/métodos , Apnea Obstructiva del Sueño/cirugía , Trastornos del Sueño-Vigilia/complicaciones , Estudios de Casos y Controles , Humanos , Procedimientos Quírurgicos Nasales , Estudios Retrospectivos , Apnea Obstructiva del Sueño/fisiopatologíaRESUMEN
The aim of this study was to assess changes in the quality of life and psychological distress of patients with tongue cancer undergoing total/subtotal glossectomy (TG) or extended hemiglossectomy (HG) and free flap transfer. Differences between the two groups were compared using the Short Form 8-Item Health Survey (SF-8) and Hospital Anxiety and Depression Scale (HADS). Of the 43 patients with tongue cancer, 24 (56%) underwent TG and 19 (44%) underwent HG. The general health and social functioning scores in the SF-8 and depression in the HADS were significantly worse in the TG group than in the HG group at 12 months after surgery, indicating that patients in the TG group may experience social isolation and psychological distress, and have difficulty in employability even 12 months after surgery. In contrast, all items of the SF-8 in the HG group were nearly equal to those in the general population. Due to the extensive psychological impact on patients with tongue cancer who are planned for an extended resection, curative surgery with free flap transfer and multidisciplinary psychiatric support are essential to improve quality of life and manage psychological distress.
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Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Distrés Psicológico , Neoplasias de la Lengua , Humanos , Glosectomía , Neoplasias de la Lengua/cirugía , Calidad de Vida , Antebrazo , Lengua/cirugíaRESUMEN
BACKGROUND: This study investigated the determinants of coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare workers (HCWs) in Cameroon and Nigeria. METHODS: This analytic cross-sectional study was conducted from May to June 2021, including consenting HCWs aged ≥18 y identified using snowball sampling. Vaccine hesitancy was defined as indecisiveness or unwillingness to receive the COVID-19 vaccine. Multilevel logistic regression yielded adjusted ORs (aORs) for vaccine hesitancy. RESULTS: We included a total of 598 (about 60% women) participants. Little or no trust in the approved COVID-19 vaccines (aOR=2.28, 95% CI 1.24 to 4.20), lower perception of the importance of the vaccine on their personal health (5.26, 2.38 to 11.6), greater concerns about vaccine-related adverse effects (3.45, 1.83 to 6.47) and uncertainty about colleagues' acceptability of the vaccine (2.98, 1.62 to 5.48) were associated with higher odds of vaccine hesitancy. In addition, participants with chronic disease (aOR=0.34, 95% CI 0.12 to 0.97) and higher levels of concerns about getting COVID-19 (0.40, 0.18 to 0.87) were less likely to be hesitant to receive the COVID-19 vaccine. CONCLUSIONS: COVID-19 vaccine hesitancy among HCWs in this study was high and broadly determined by the perceived risk of COVID-19 and COVID-19 vaccines on personal health, mistrust in COVID-19 vaccines and uncertainty about colleagues' vaccine acceptability.
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Vacunas contra la COVID-19 , COVID-19 , Femenino , Humanos , Masculino , Camerún/epidemiología , Estudios Transversales , Nigeria/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Personal de Salud , Internet , VacunaciónRESUMEN
AIMS/HYPOTHESIS: The aim of this study was to generate induced pluripotent stem (iPS) cells from patients with mitochondrial DNA (mtDNA) mutation. METHODS: Skin biopsies were obtained from two diabetic patients with mtDNA A3243G mutation. The fibroblasts thus obtained were infected with retroviruses encoding OCT4 (also known as POU5F1), SOX2, c-MYC (also known as MYC) and KLF4. The stem cell characteristics were investigated and the mtDNA mutation frequencies evaluated by Invader assay. RESULTS: From the two diabetic patients we isolated four and ten putative mitochondrial disease-specific iPS (Mt-iPS) clones, respectively. Mt-iPS cells were cytogenetically normal and positive for alkaline phosphatase activity, with the pluripotent stem cell markers being detectable by immunocytochemistry. The cytosine guanine dinucleotide islands in the promoter regions of OCT4 and NANOG were highly unmethylated, indicating epigenetic reprogramming to pluripotency. Mt-iPS clones were able to differentiate into derivatives of all three germ layers in vitro and in vivo. The Mt-iPS cells exhibited a bimodal degree of mutation heteroplasmy. The mutation frequencies decreased to an undetectable level in six of 14 clones, while the others showed several-fold increases in mutation frequencies (51-87%) compared with those in the original fibroblasts (18-24%). During serial cell culture passage and after differentiation, no recurrence of the mutation or no significant changes in the levels of heteroplasmy were seen. CONCLUSIONS/INTERPRETATION: iPS cells were successfully generated from patients with the mtDNA A3243G mutation. Mutation-rich, stable Mt-iPS cells may be a suitable source of cells for human mitochondrial disease modelling in vitro. Mutation-free iPS cells could provide an unlimited, disease-free supply of cells for autologous transplantation therapy.
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ADN Mitocondrial/genética , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Fosfatasa Alcalina/metabolismo , Técnicas de Cultivo de Célula , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Cuerpos Embrioides/citología , Fibroblastos/citología , Humanos , Inmunohistoquímica , Cariotipo , Factor 4 Similar a Kruppel , Repeticiones de Microsatélite/genética , MutaciónRESUMEN
Sudden sensorineural hearing loss (SSNHL) and Ménière's disease are the most common inner ear diseases in which the causes are unknown. As recent magnetic resonance imaging has demonstrated disruption of the blood-labyrinth barrier in these inner ear diseases, inflammatory reaction associated with increased permeability of the blood vessels may be involved. The genotypes of interleukin 1A (IL1A) (-889C/T; rs1800587) and interleukin 1B (IL1B) (-511C/T; rs16944) were determined using an allele-specific primer-polymerase chain reaction method in 72 patients with SSNHL, 68 patients with Ménière's disease, and 2202 control subjects living almost in the same area as the patients. A significantly higher prevalence of the IL1A-889T allele was observed in SSNHL and Ménière's disease compared with controls, although no significant difference in distribution of IL1B-511C/T genotypes was observed between the patients and controls. Adjusted odd ratios for SSNHL and Ménière's disease risks in the -889TT genotypes were 25.89 (95% confidence interval (CI) 12.19-54.98) and 18.20 (95% CI 7.80-42.46), respectively, after age and gender were taken as moderator variables. Our results suggested that IL1A is closely associated with susceptibility of SSNHL and Ménière's disease.
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Pérdida Auditiva Súbita/genética , Interleucina-1/genética , Enfermedad de Meniere/genética , Polimorfismo Genético , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In the head and neck region, preoperative evaluation of the free flap volume is challenging. The current study validated preoperative three-dimensional (3D) virtual surgical simulation for soft tissue reconstruction by assessing flap volume and evaluated fat and muscle volume changes at follow-up in 13 head and neck cancer patients undergoing anterolateral craniofacial resection. Patients received 3D virtual surgical simulation, and the volume of the planned defects was estimated by surgical simulation. Following en bloc resection of the tumor, the defect in the skull base was covered using a rectus abdominis myocutaneous flap. Following surgery, computed tomography scans were acquired at day 1 and at 6 and 12 months. Virtual planned defect was on average 227 ml (range, 154-315) and was 10% smaller than the actual flap volume in patients without skin involvement of the tumor. Between day 1 and 12 months post-surgery, the volume of fat and muscle tissue in the free flap dropped by 9% and 58%, respectively. Our results indicate that 3D virtual surgical simulation provides essential information in determining the accurate volume of the required free flap for surgical defect repair and may thus help improve surgical planning and functional and esthetic outcome.
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Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello , Colgajo Miocutáneo , Procedimientos de Cirugía Plástica , Estética Dental , Estudios de Factibilidad , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/cirugía , HumanosRESUMEN
BACKGROUND AND PURPOSE: Metal artifacts reduce the quality of CT images and increase the difficulty of interpretation. This study compared the ability of model-based iterative reconstruction and hybrid iterative reconstruction to improve CT image quality in patients with metallic dental artifacts when both techniques were combined with a metal artifact reduction algorithm. MATERIALS AND METHODS: This retrospective clinical study included 40 patients (men, 31; women, 9; mean age, 62.9 ± 12.3 years) with oral and oropharyngeal cancer who had metallic dental fillings or implants and underwent contrast-enhanced ultra-high-resolution CT of the neck. Axial CT images were reconstructed using hybrid iterative reconstruction and model-based iterative reconstruction, and the metal artifact reduction algorithm was applied to all images. Finally, hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithm data were obtained. In the quantitative analysis, SDs were measured in ROIs over the apex of the tongue (metal artifacts) and nuchal muscle (no metal artifacts) and were used to calculate the metal artifact indexes. In a qualitative analysis, 3 radiologists blinded to the patients' conditions assessed the image-quality scores of metal artifact reduction and structural depictions. RESULTS: Hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithms yielded significantly different metal artifact indexes of 82.2 and 73.6, respectively (95% CI, 2.6-14.7; P < .01). The latter algorithms resulted in significant reduction in metal artifacts and significantly improved structural depictions(P < .01). CONCLUSIONS: Model-based iterative reconstruction + metal artifact reduction algorithms significantly reduced the artifacts and improved the image quality of structural depictions on neck CT images.
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Algoritmos , Artefactos , Interpretación de Imagen Asistida por Computador/métodos , Metales , Neoplasias Orofaríngeas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Boca/diagnóstico por imagen , Prótesis e Implantes , Estudios RetrospectivosRESUMEN
INTRODUCTION: Anaemia, especially in children aged <5 years, is a global health problem disproportionately affecting populations in low-income and middle-income countries. It is associated with high disability and death rates and has a negative effect on development. This study seeks to evaluate the prevalence and determinants of anaemia in children aged 6-59 months residing in Africa. METHODS AND ANALYSIS: This protocol was prepared using the 2015 Preferred Reporting Items for Systematic Reviews and Meta-analyses for Protocols guidelines. Relevant citations will be identified by searching EMBASE, Web of Science, PubMed, Global Medicus Index and African Journals Online from inception to 30 September 2019 with no language restrictions. Two authors will independently screen and select eligible studies for the review. Random-effect meta-analytic methods will be used to pool study-specific estimates and heterogeneity will be assessed and quantified using the χ2 test on Cochrane's Q and I2 statistics, respectively. Publication bias will be evaluated using funnel plots and Egger's test. Subgroup analysis and multiple meta-regression using backward elimination will be performed to investigate sources of substantial heterogeneity. ETHICS AND DISSEMINATION: No ethical approval is required for this study as it is based on already published data. The findings of the review will be published in a peer-reviewed journal and presented at conferences.
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Anemia , Preescolar , Humanos , Lactante , África/epidemiología , Anemia/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Estudios Transversales , Prevalencia , Sesgo de Publicación , Ensayos Clínicos Controlados Aleatorios como Asunto , Metaanálisis como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: The safety and efficacy of percutaneous vertebroplasty (PVP), a new treatment modality for painful malignant vertebral compression fractures (PMVCF) using interventional radiology techniques, were evaluated prospectively. MATERIALS AND METHODS: After confirming the absence of safety issues in phase 1, a total of 33 cases were registered up to and including phase 2. Safety and efficacy were evaluated by National Cancer Institute-Common Toxicity Criteria version 2 and Visual Analogue Scale (VAS) at 1 week after PVP. Based on VAS score decreases, efficacy was classified into significantly effective (SE; > or = 5 or reached 0-2), moderately effective (ME; 2-4), or ineffective (NE; <2 or increase). RESULTS: Procedures were completed in all 33 patients (42 vertebrae). Thirty days after PVP, two patients died of primary disease progression, but no major adverse reactions (>grade 2) were observed. Response rate was 70% (95% confidence interval 54% to 83%) [61% (n = 20) with SE, 9% (n = 3) with ME, and 30% (n = 10) with NE] and increased to 83% at week 4. Median time to response was 1 day (mean 2.4). Median pain-mitigated survival period was 73 days. CONCLUSION: For PMVCF, PVP is a safe and effective treatment modality with immediate onset of action.
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Neoplasias Óseas/complicaciones , Fracturas por Compresión/terapia , Cuidados Paliativos , Fracturas de la Columna Vertebral/terapia , Vertebroplastia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fracturas por Compresión/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Fracturas de la Columna Vertebral/complicaciones , Vertebroplastia/efectos adversosRESUMEN
The morphology of axon terminals changes with differentiation into mature synapses. A molecule that might regulate this process was identified by a screen of Drosophila mutants for abnormal motor activities. The still life (sif) gene encodes a protein homologous to guanine nucleotide exchange factors, which convert Rho-like guanosine triphosphatases (GTPases) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The SIF proteins are found adjacent to the plasma membrane of synaptic terminals. Expression of a truncated SIF protein resulted in defects in neuronal morphology and induced membrane ruffling with altered actin localization in human KB cells. Thus, SIF proteins may regulate synaptic differentiation through the organization of the actin cytoskeleton by activating Rho-like GTPases.
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Proteínas de Drosophila , Drosophila/metabolismo , Factores de Intercambio de Guanina Nucleótido , Terminales Presinápticos/metabolismo , Proteínas de Unión al GTP rac , Actinas/metabolismo , Secuencia de Aminoácidos , Animales , Axones/fisiología , Membrana Celular/ultraestructura , Citoesqueleto/fisiología , Citoesqueleto/ultraestructura , ADN Complementario/genética , Drosophila/embriología , Drosophila/genética , Embrión no Mamífero/metabolismo , GTP Fosfohidrolasas/metabolismo , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo , Expresión Génica , Genes de Insecto , Humanos , Hibridación in Situ , Células KB , Datos de Secuencia Molecular , Movimiento , Mutación , Unión Neuromuscular/metabolismo , Transducción de SeñalRESUMEN
We identified the Drosophila trio gene, which encodes a Dbl family protein carrying two Dbl homology (DH) domains, each of which potentially activates Rho family GTPases. Trio was distributed along axons in the central nervous system (CNS) of embryos and was strongly expressed in subsets of brain regions, including the mushroom body (MB). Loss-of-function trio mutations resulted in the misdirection or stall of axons in embryos and also caused malformation of the MB. The MB phenotypes were attributed to alteration in the intrinsic nature of neurites, as revealed by clonal analyses. Thus, Trio is essential in order for neurites to faithfully extend on the correct pathways. In addition, the localization of Trio in the adult brain suggests its postdevelopmental role in neurite terminals.
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Axones/fisiología , Sistema Nervioso Central/embriología , Proteínas de Drosophila , Conos de Crecimiento/fisiología , Factores de Intercambio de Guanina Nucleótido , Neuritas/fisiología , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinasas/genética , Animales , Sistema Nervioso Central/fisiología , Drosophila/genética , Datos de Secuencia Molecular , Oligoquetos/genética , Fosfoproteínas/fisiología , Proteínas Serina-Treonina Quinasas/fisiologíaRESUMEN
BACKGROUND: Malaria remains a major public health problem in most tropical countries. It occasionally presents with both typical and atypical signs and symptoms. Gastrointestinal manifestations are common in malaria endemic areas but intestinal obstruction as a complication is extremely rare. CASE PRESENTATION: We present the case of a 42-year-old black African man who presented with signs and symptoms of intestinal obstruction and was diagnosed as having Plasmodium falciparum malaria. He was successfully treated with both parenteral and orally administered antimalarial medication and the intestinal obstruction subsequently resolved. CONCLUSION: With intestinal obstruction being an important cause of morbidity and mortality, we report this case to highlight this rare complication of malaria and therefore increase physicians' awareness and prompt diagnosis and management.
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Obstrucción Intestinal/parasitología , Malaria Falciparum/complicaciones , Adulto , Antimaláricos/uso terapéutico , Humanos , Obstrucción Intestinal/etiología , Malaria Falciparum/diagnóstico , Malaria Falciparum/tratamiento farmacológico , MasculinoRESUMEN
OBJECTIVES: We introduce "Mobile Nurse" (MN) - an emerging platform for the practice of ubiquitous medicine. METHODS: By implementing in a dynamic setting of daily life the patient care traditionally provided by the clinical nurses on duty, MN aims at integral data collection and shortening the response time to the patient. MN is also capable of intelligent interaction with the patient and is able to learn from the patient's behavior and disease sign evaluation for improved personalized treatment. RESULTS: In this paper, we outline the most essential concepts around the hardware, software and methodological designs of MN. We provide an example of the implementation, and elaborate on the possible future impact on medical practice and biomedical science research. CONCLUSIONS: The main innovation of MN, setting it apart from current tele-medicine systems, is the ability to integrate the patient's signs and symptoms on site, providing medical professionals with powerful tools to elucidate disease mechanisms, to make proper diagnoses and to prescribe treatment.
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Computadoras de Mano , Monitoreo Ambulatorio/instrumentación , Enfermeras Clínicas , Telemetría/instrumentación , Sistemas de Computación , Humanos , Unidades Móviles de Salud , Procesamiento de Señales Asistido por ComputadorRESUMEN
BACKGROUND: Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. METHODS AND RESULTS: Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81+/-0.05 versus 0.30+/-0.14, P<0.01) and at 28 days (0.96+/-0.01 versus 0.45+/-0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. CONCLUSIONS: Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.
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Endotelio Vascular/metabolismo , Transferencia de Gen Horizontal , Oclusión de Injerto Vascular/prevención & control , Venas Yugulares/trasplante , Péptido Natriurético Tipo-C/metabolismo , Trombosis/prevención & control , Adenoviridae/genética , Animales , Arterias Carótidas/cirugía , Células Cultivadas , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Humanos , Técnicas In Vitro , Venas Yugulares/efectos de los fármacos , Venas Yugulares/metabolismo , Masculino , Péptido Natriurético Tipo-C/genética , Péptido Natriurético Tipo-C/farmacología , Conejos , Ratas , Trasplante Autólogo , Resultado del Tratamiento , Túnica Íntima/citología , Túnica Íntima/efectos de los fármacos , Grado de Desobstrucción Vascular/efectos de los fármacosRESUMEN
Vascular endothelial growth factor (VEGF) has been recognized as an angiogenic factor that induces endothelial proliferation and vascular permeability. Recent studies have also suggested that VEGF can promote macrophage migration, which is critical for atherosclerosis. We have reported that VEGF is remarkably expressed in activated macrophages, endothelial cells, and smooth muscle cells within human coronary atherosclerotic lesions, and we have proposed the significance of VEGF in the progression of atherosclerosis. To clarify the mechanism of VEGF expression in atherosclerotic lesions, we examined the regulation of VEGF expression by oxidized low density lipoprotein (Ox-LDL), which is abundant in atherosclerotic arterial walls. A recent report has revealed that peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed not only in adipocytes but also in monocytes/macrophages and has suggested that PPARgamma may have a role in the differentiation of monocytes/macrophages. Furthermore, 9- and 13-hydroxy-(S)-10,12-octadecadienoic acid (9- and 13-HODE, respectively), the components of Ox-LDL, may be PPARgamma ligands. Therefore, we investigated the involvement of PPARgamma in the regulation of VEGF by Ox-LDL. PPARgamma expression was detected in human monocyte/macrophage cell lines, human acute monocytic leukemia (THP-1) cells, and human coronary artery endothelial cells (HCAECs). Ox-LDL (10 to 50 microg/mL) upregulated VEGF secretion from THP-1 dose-dependently. VEGF mRNA expression in HCAECs was also upregulated by Ox-LDL. The mRNA expression of VEGF in THP-1 cells and HCAECs was also augmented by PPARgamma activators, troglitazone (TRO), and 15-deoxy-(12,14)-prostaglandin J(2) (PGJ2). In contrast, VEGF expression in another monocyte/macrophage cell line, human histiocytic lymphoma cells (U937), which lacks PPARgamma expression, was not augmented by TRO or PGJ2. We established the U937 cell line, which permanently expresses PPARgamma (U937T). TRO and Ox-LDL augmented VEGF expression in U937T. In addition, VEGF production by THP-1 cells was significantly increased by exposure to 9-HODE and 13-HODE. In conclusion, Ox-LDL upregulates VEGF expression in macrophages and endothelial cells, at least in part, through the activation of PPARgamma.
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Arteriosclerosis/metabolismo , Factores de Crecimiento Endotelial/biosíntesis , Endotelio Vascular/metabolismo , Lipoproteínas LDL/metabolismo , Linfocinas/biosíntesis , Macrófagos/metabolismo , Movimiento Celular , Factores de Crecimiento Endotelial/metabolismo , Endotelio Vascular/fisiología , Humanos , Lipoproteínas LDL/fisiología , Linfocinas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
We recently reported that C-type natriuretic peptide (CNP) occurs in vascular endothelial cells and acts as a vascular-type natriuretic peptide. In the present study, we stimulated the cGMP cascade in proliferating smooth muscle cells (SMCs), in which particulate guanylate cyclase-B, the specific receptor for CNP, is predominantly expressed, by use of an adenovirus encoding rat CNP cDNA (Ad.CNP). In the Ad.CNP-treated cultured SMCs, CNP caused the growth inhibition of SMCs at G(1) phase with an early increase of p21(CIP1/WAF1) expression and subsequent upregulation of p16(INK4a). The expression of smooth muscle myosin heavy chain-2, which is the molecular marker of highly differentiated SMCs, was reinduced in the Ad.CNP-treated SMCs. The Ad.CNP-treated SMCs also reexpressed particulate guanylate cyclase-A, which shows high affinity to atrial and brain natriuretic peptide and is exclusively expressed in well-differentiated SMCs. CNP, which was overexpressed in rabbit femoral arteries in vivo at the time of balloon injury, significantly suppressed neointimal formation. Furthermore, an enhancement of the expression of smooth muscle myosin heavy chain-2 occurred in the residual neointima. In addition, early regeneration of endothelial cells was observed in the Ad.CNP-infected group. Thus, stimulation of cGMP cascade in proliferating dedifferentiated SMCs can induce growth inhibition and redifferentiation of SMCs with accelerated reendothelialization.
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Endotelio Vascular/fisiología , Músculo Liso Vascular/citología , Péptido Natriurético Tipo-C/fisiología , Adenoviridae/genética , Angiografía , Animales , Arterias/patología , Arteriosclerosis/etiología , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Cateterismo/efectos adversos , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/genética , Diferenciación Celular , Células Cultivadas , Masculino , Músculo Liso Vascular/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Péptido Natriurético Tipo-C/genética , ARN Mensajero/biosíntesis , Conejos , Ratas , Regeneración , TransfecciónRESUMEN
OBJECTIVE: To report magnetic resonance imaging findings in a patient with an SLC26A4 gene mutation who had low-frequency sensorineural hearing loss. CASE REPORT: A 13-year-old girl had bilateral and symmetric low-frequency sensorineural hearing loss. Upon genetic testing, a heterozygous c.1105A > G (p.K369E) mutation of the SLC26A4 gene was detected. Mild endolymphatic hydrops in the right cochlea and marked endolymphatic hydrops in the left vestibulum were seen by magnetic resonance imaging 4 hours after an intravenous gadolinium injection. CONCLUSION: This is the first reported case of a patient with the SLC26A4 gene mutation c.1105A > G (p.K369E) who had low-frequency sensorineural hearing loss. Co-occurrence of cochlear and vestibular endolymphatic hydrops suggests an association with that pathology.
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Hidropesía Endolinfática/genética , Pérdida Auditiva Bilateral/genética , Pérdida Auditiva Sensorineural/genética , Proteínas de Transporte de Membrana/genética , Adolescente , Femenino , Humanos , Imagen por Resonancia Magnética , Mutación , Transportadores de SulfatoRESUMEN
The tissue-nonspecific alkaline phosphatase (TNSALP) gene from five German family members with childhood-type hypophosphatasia (HOPS) was analyzed using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)-direct sequencing method. Four novel missense mutations (T51M, R54S, L258P, and R374H) and two that had been described previously (A160T and R206W) were detected in the respective patients. Mutation A160T was detected in 3 distinct patients, and a polymorphism V505A that had been described previously was detected in the same allele as L258P mutation in 1 patient and in 2 fathers whose V505A alleles were not transmitted to the probands. No other mutations were found in 2 patients. Transient expression of the mutant proteins in COS-1 cells showed that the four novel mutations and R206W were severe alleles, whereas A160T was a moderate allele. Analysis of its enzymatic activity and genetic transmission patterns confirmed that V505A was a polymorphism. Immunoprecipitation of the transiently expressed proteins showed that levels of the 80-kDa mature form of the enzyme were diminished or absent with the severe alleles; instead, levels of high-molecular mass disulfide-linked aggregates were increased. These results suggest that in compound heterozygotes, the combination of severe and moderate alleles may combine to cause the mild phenotype seen in childhood-type HOPS.