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1.
Respiration ; 102(1): 64-73, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36412608

RESUMEN

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have difficulties inhaling as the diaphragm becomes flattened and weakened due to lung hyperinflation. This weakened respiratory function is compensated for by the increased activity of the accessory respiratory muscles, such as the sternocleidomastoid muscle (SCM). OBJECTIVES: This study aimed to evaluate the difference in the SCM thickening fraction (SCM TF) of each respiratory phase (end-expiration, resting inspiration, and end-inspiration), as measured using ultrasonography (US), between patients with COPD and control subjects. We also evaluate the correlation between the SCM TF of each respiratory phase and exercise tolerance in patients with COPD. METHODS: Patients with COPD (n = 44) and age-matched controls (n = 20) underwent US for determination of the SCM TF. Ventilation parameters, including the peak oxygen uptake (peak VO2) and the change in the inspiratory capacity, were measured during cardiopulmonary exercise testing. The SCM thickness and TF was measured during end-expiration, resting breathing, and end-inspiration. RESULTS: The SCM was significantly thinner in patients with COPD than in controls at end-expiration. The increase in the SCM TF from end-expiration to end-inspiration in patients with COPD did not differ significantly from that in control subjects. In contrast, the SCM TF from end-expiration to resting inspiration was significantly greater in patients with COPD than in control subjects. The peak VO2 was strongly positively correlated with the SCM TF from end-expiration to end-inspiration in patients with COPD (r = 0.71, p < 0.01). CONCLUSIONS: The SCM may be thinner in patients with COPD than in controls. The SCM TF may also be associated with exercise tolerance.


Asunto(s)
Tolerancia al Ejercicio , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Tolerancia al Ejercicio/fisiología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Pulmón , Diafragma/diagnóstico por imagen , Músculos Respiratorios
2.
Dysphagia ; 37(3): 636-643, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34036401

RESUMEN

Dysphagia is frequently observed in patients with chronic obstructive pulmonary disease (COPD). Decreased tongue strength is one of the causes of dysphagia, and it is often observed in patients with sarcopenia. Sarcopenia is also frequently observed in COPD patients. We hypothesized that tongue strength is lower in COPD patients compared to normal subjects. This was a single-center, observational, cross-sectional study. Maximum tongue pressure (MTP) was measured in 27 patients with COPD and 24 age-matched control subjects. We also evaluated handgrip strength, gait speed, and appendicular skeletal muscle mass to define subjects as having sarcopenia. We used bioelectrical impedance analysis to assess body composition. The eating assessment test-10 was used to diagnose dysphagia. MTP was significantly lower in COPD patients than in control subjects (33.8 ± 8.4 vs 38.0 ± 5.3; p = 0.032). All measures of muscle and fat free body mass, handgrip strength, and gait speed were also significantly lower in COPD patients compared to control subjects (p < 0.01). The prevalence of sarcopenia in COPD patients was higher than that in control subjects (6/27 versus 0/24; p = 0.007), but the prevalence of dysphagia was not different between groups (COPD: 5/27, versus control: 1/24; p = 0.112). MTP was moderately correlated with skeletal muscle mass index (r = 0.56, p = 0.003) and handgrip strength (r = 0.43, p = 0.027) in COPD patients. Tongue strength was lower in COPD patients compared to normal subjects, and decreased tongue strength may be correlated with sarcopenia in COPD patients.


Asunto(s)
Trastornos de Deglución , Enfermedad Pulmonar Obstructiva Crónica , Sarcopenia , Estudios Transversales , Fuerza de la Mano/fisiología , Humanos , Fuerza Muscular/fisiología , Músculo Esquelético , Presión , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Sarcopenia/etiología , Lengua
3.
Respir Res ; 22(1): 271, 2021 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-34686189

RESUMEN

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the maximum level of diaphragm excursion (DEmax) is correlated with dynamic lung hyperinflation and exercise tolerance. This study aimed to elucidate the utility of DEmax to predict the improvement in exercise tolerance after pulmonary rehabilitation (PR) in patients with COPD. METHODS: This was a prospective cohort study. Of the 62 patients with stable COPD who participated in the outpatient PR programme from April 2018 to February 2021, 50 completed the programme. Six-minute walk distance (6MWD) was performed to evaluate exercise tolerance, and ultrasonography was performed to measure DEmax. Responders to PR in exercise capacity were defined as patients who demonstrated an increase of > 30 m in 6MWD. The receiver operating characteristic (ROC) curve was used to determine the cut-off point of DEmax to predict responses to PR. RESULTS: Baseline levels of forced expiratory volume in 1 s, 6MWD, maximum inspiratory pressure, DEmax and quadriceps muscle strength were significantly higher, and peak dyspnoea of modified Borg (mBorg) scale score was lower in responders (n = 30) than in non-responders (n = 20) to PR (p < 0.01). In multivariate analysis, DEmax was significantly correlated with an increase of > 30 m in 6MWD. The area under the ROC curve of DEmax to predict responders was 0.915, with a sensitivity and specificity of 83% and 95%, respectively, at a cut-off value of 44.9 mm of DEmax. CONCLUSION: DEmax could adequately predict the improvement in exercise tolerance after PR in patients with COPD.


Asunto(s)
Diafragma/fisiopatología , Terapia por Ejercicio , Tolerancia al Ejercicio , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Anciano , Anciano de 80 o más Años , Toma de Decisiones Clínicas , Diafragma/diagnóstico por imagen , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Recuperación de la Función , Entrenamiento de Fuerza , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía , Prueba de Paso , Caminata
4.
Biochem Biophys Res Commun ; 523(3): 707-712, 2020 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-31948758

RESUMEN

Removal of dysfunctional mitochondria is essential step to maintain normal cell physiology, and selective autophagy in mitochondria, called mitophagy, plays a critical role in quality control of mitochondria. While in several diseases and aging, disturbed mitophagy has been observed. In stem cells, accumulation of damaged mitochondria can lead to deterioration of stem cell properties. Here, we focused on miR-155-5p (miR-155), one of the most prominent miRNAs in inflammatory and aged tissues, and found that miR-155 disturbed mitophagy in mesenchymal stem cells (MSCs). As a molecular mechanism of miR-155-mediated mitophagy suppression, we found that BCL2 associated athanogene 5 (BAG5) is a direct target of miR-155. Reduction of BAG5 resulted in destabilization of PTEN-induced kinase (PINK1) and consequently disrupted mitophagy. Our study suggests a novel mechanism connecting aging and aging-associated inflammation with mitochondrial dysfunction in stem cells through a miRNA-mediated mechanism.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , Mitofagia , Proteínas Quinasas/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Envejecimiento , Animales , Línea Celular , Células Cultivadas , Regulación hacia Abajo , Humanos , Masculino , Células Madre Mesenquimatosas/citología , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Mapas de Interacción de Proteínas , Proteínas Quinasas/metabolismo , Regulación hacia Arriba
5.
Stem Cells ; 37(12): 1595-1605, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31461199

RESUMEN

Bone marrow-derived mesenchymal stem cells (BMMSCs) are multipotent stem cells capable of differentiation into a variety of cell types, proliferation, and production of clinically useful secretory factors. These advantages make BMMSCs highly useful for cell transplantation therapy. However, the molecular network underlying BMMSC proliferation remains poorly understood. Here, we showed that TGFß-activated kinase 1 (Tak1) is a critical molecule that regulates the activation of cell cycling and that Tak1 inhibition leads to quiescence in BMMSCs both in vivo and in vitro. Mechanistically, Tak1 was phosphorylated by growth factor stimulations, allowing it to bind and stabilize Yap1/Taz, which could then be localized to the nucleus. We also demonstrated that the quiescence induction by inhibiting Tak1 increased oxidized stress tolerance and improved BMMSC engraftment in intramuscular and intrabone marrow cell transplantation models. This study reveals a novel pathway controlling BMMSC proliferation and suggests a useful method to improve the therapeutic effect of BMMSC transplantation. Stem Cells 2019;37:1595-1605.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Ciclo Celular/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Células Madre Mesenquimatosas/fisiología , Transactivadores/metabolismo , Animales , Células de la Médula Ósea/citología , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Humanos , Quinasas Quinasa Quinasa PAM/genética , Masculino , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos C57BL , Fosforilación , Regeneración/fisiología , Proteínas Señalizadoras YAP
6.
J Phys Ther Sci ; 32(4): 297-302, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32273654

RESUMEN

[Purpose] Discrimination between end-feel types is difficult, and years of clinical experience is considered a factor for improving the accuracy of the discrimination. The present study investigated whether the accuracy of classification of end-feel types improves with the increase in years of clinical experience. [Participants and Methods] In total, 44 therapists (range of years of clinical experience: 1-26 years) and 13 students were included. The participants identified the type of end feel simulated by our newly developed simulator. The proportion of correct answers of the therapists was compared with that of the students. For the therapists, years of clinical experience and their awareness of end feel were examined, and their relationships with the ability to classify end-feel types were analyzed. [Results] The therapists showed a higher ability to identify end-feel type than the students. The ability of the therapists improved according to their years of clinical experience. The cutoff values for years of clinical experience to improve the ability for identifying bone-to-bone, muscular, and tissue approximations were 15, 6, and 15, respectively. The therapists who were always conscious about end feel were associated with a higher ability to classify end-feel types. [Conclusion] Our present study demonstrated that the ability to classify end feel improves with the increase in years of clinical experience.

7.
Calcif Tissue Int ; 105(1): 97-106, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30993375

RESUMEN

A disintegrin and metalloproteinase 12 (ADAM12) is known to be involved in chondrocyte proliferation and maturation; however, the mechanisms are not fully understood. In this study, expression and localization of ADAM12 during chondrocyte differentiation were examined in the mouse growth plate by immunohistochemistry. Adam12 expression during ATDC5 chondrogenic differentiation was examined by real-time PCR and compared with the expression pattern of type X collagen. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system was used to generate Adam12-knockout (KO) ATDC5 cells. Adam12-KO and Adam12 overexpressing cells were used for analyses of ADAM12 expression with or without TGF-ß1 stimulation. ADAM12 was identified predominantly in chondrocytes of the proliferative zone in mouse growth plates by immunohistochemistry. Adam12 was upregulated prior to Col10a1 during chondrogenic differentiation in wild-type ATDC5 cells. In Adam12-KO ATDC5 cells, following initiation of chondrogenic differentiation, we observed a reduction in Igf-1 expression along with an upregulation of hypertrophy-associated Runx2, Col10a1, and type X collagen protein expressions. In ATDC5 wild-type cells, stimulation with TGF-ß1 upregulated the expressions of Adam12 and Igf-1 and downregulated the expression of Runx2. In contrast, in Adam12-KO ATDC5 cells, these TGF-ß1-induced changes were suppressed. Adam12 overexpression resulted in an upregulation of Igf-1 and downregulation of Runx2 expression in ATDC5 cells. The findings suggest that ADAM12 has important role in the regulation of chondrocyte differentiation, potentially by regulation of TGF-ß1-dependent signaling and that targeting of ADAM12 may have a role in management of abnormal chondrocyte differentiation.


Asunto(s)
Proteína ADAM12/metabolismo , Diferenciación Celular/fisiología , Condrocitos/citología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Células Cultivadas , Condrogénesis/fisiología , Colágeno Tipo II/metabolismo , Colágeno Tipo X/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo
8.
Biochem Biophys Res Commun ; 503(4): 3114-3120, 2018 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-30143262

RESUMEN

Purification of undifferentiated cells by removing differentiated parts is an essential step in pluripotent stem cell culture. This process has been traditionally performed manually using a fine glass capillary or plastic tip under a microscope, or by culturing in a selective medium supplemented with anti-differentiation inhibitors. However, there are several inevitable problems associated with these methods, such as contamination or biological side-effects. Here, we developed a laser-assisted cell removing (LACR) technology that enables precise, fast, and contact-less cell removal. Using LACR combined with computational image recognition/identification-discriminating technology, we achieved automatic cell purification (A-LACR). Practicability of A-LACR was evaluated by two demonstrations: selective removal of trophoblast stem (TS) cells from human iPS and TS cell co-cultures, and purification of undifferentiated iPS cells by targeting differentiated cells that spontaneously developed. Our results suggested that LACR technology is a novel approach for stem cell processing in regenerative medicine.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes/citología , Trofoblastos/citología , Animales , Muerte Celular/efectos de la radiación , Diferenciación Celular , Línea Celular , Técnicas de Cocultivo/métodos , Humanos , Células Madre Pluripotentes Inducidas/efectos de la radiación , Rayos Infrarrojos/efectos adversos , Rayos Láser/efectos adversos , Ratones , Células Madre Pluripotentes/efectos de la radiación , Medicina Regenerativa , Trofoblastos/efectos de la radiación
9.
Eur Respir J ; 46(6): 1615-24, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26493791

RESUMEN

This study was designed to investigate the association of perceived dyspnoea intensity with cortical oxygenation and cortical activation during exercise in patients with chronic obstructive pulmonary disease (COPD) and exertional hypoxaemia.Low-intensity exercise was performed at a constant work rate by patients with COPD and exertional hypoxaemia (n=11) or no hypoxaemia (n=16), and in control participants (n=11). Cortical oxyhaemoglobin (oxy-Hb) and deoxyhaemoglobin (deoxy-Hb) concentrations were measured by multichannel near-infrared spectroscopy. Increased deoxy-Hb is assumed to reflect impaired oxygenation, whereas decreased deoxy-Hb signifies cortical activation.Exercise decreased cortical deoxy-Hb in control and nonhypoxaemic patients. Deoxy-Hb was increased in hypoxaemic patients and oxygen supplementation improved cortical oxygenation. Decreased deoxy-Hb in the pre-motor cortex (PMA) was significantly correlated with exertional dyspnoea in control participants and patients with COPD without hypoxaemia. In contrast, increased cortical deoxy-Hb concentration was correlated with dyspnoea in patients with COPD and hypoxaemia. With the administration of oxygen supplementation, exertional dyspnoea was correlated with decreased deoxy-Hb in the PMA of COPD patients with hypoxaemia.During exercise, cortical oxygenation was impaired in patients with COPD and hypoxaemia compared with control and nonhypoxaemic patients; this difference was ameliorated with oxygen supplementation. Exertional dyspnoea was related to activation of the pre-motor cortex in COPD patients.


Asunto(s)
Corteza Cerebral/metabolismo , Disnea/metabolismo , Hipoxia/metabolismo , Oxígeno/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Anciano , Estudios de Casos y Controles , Disnea/fisiopatología , Tolerancia al Ejercicio/fisiología , Volumen Espiratorio Forzado , Hemoglobinas/metabolismo , Humanos , Hipoxia/fisiopatología , Masculino , Oxihemoglobinas/metabolismo , Esfuerzo Físico/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Espectroscopía Infrarroja Corta , Capacidad Vital
11.
Clin Endocrinol (Oxf) ; 80(3): 362-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23418907

RESUMEN

OBJECTIVE: Butyrylcholinesterase is synthesized in the liver. The serum butyrylcholinesterase level has been cross-sectionally reported to be higher in patients with diabetes, hyperlipidaemia, obesity and fatty liver than in those without them. It is not known whether serum butyrylcholinesterase is associated with the risk of future type 2 diabetes. DESIGN: A prospective cohort study. PARTICIPANTS: A total of 8470 Japanese men aged 40-55 years without type 2 diabetes at baseline. MEASUREMENTS: Type 2 diabetes was diagnosed if a fasting plasma glucose (FPG) level was ≥7·0 mmol/l, if a HbA1 c level was ≥6·5% or if participants were taking oral hypoglycaemic medication or insulin. RESULTS: During the 42,227 person-years of follow-up, 868 cases had developed type 2 diabetes. Serum butyrylcholinesterase was significantly positively correlated with body mass index (BMI), FPG, alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and triglycerides (TG), whereas negatively with high-density lipoprotein (HDL) cholesterol. In Cox proportional hazards models, after adjusting for age, BMI, FPG, alcohol consumption, smoking habit, walk to work, regular leisure-time physical activity and family history of diabetes, the highest quartile (398-806 IU/l) of serum butyrylcholinesterase increased the risk of type 2 diabetes compared with the lowest quartile (56-311 IU/l) [hazard ratio (HR) 1·41 (95% confidence interval (CI), 1·14-1·74)]. After further adjusting for ALT and GGT, this association remained [HR 1·40 (95% CI, 1·13-1·73)]. Furthermore, this association was significant independent of TG and HDL cholesterol. CONCLUSIONS: Elevated serum butyrylcholinesterase was independently associated with an increased risk of future type 2 diabetes.


Asunto(s)
Butirilcolinesterasa/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etiología , Adulto , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Hígado Graso/sangre , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Obesidad/epidemiología , Pronóstico , Factores de Riesgo
12.
Am J Nephrol ; 40(6): 516-22, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25531762

RESUMEN

BACKGROUND/AIMS: The association between alcohol consumption and the risk of chronic kidney disease (CKD) has been reported. What is not known is whether drinking pattern combined with the weekly frequency of alcohol consumption and the quantity per drinking day is associated with the risk of CKD. METHODS: We enrolled 9,112 Japanese nondiabetic men aged 40 to 55 years with absence of proteinuria, an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m(2) or higher, and not on antihypertensive medications at baseline. CKD was defined if eGFR was <60 ml/min/1.73 m(2). The weekly frequency classification was nondrinkers, 1-3 drinking days/week, or 4-7 drinking days/week. The quantity consumed per drinking day was classified as 0.1-23.0 g ethanol/drinking day, 23.1-46.0 g ethanol/drinking day, 46.1-69.0 g ethanol/drinking day, and ≥69.1 g ethanol/drinking day. RESULTS: During the 79,099 person-years, 1,253 subjects developed CKD. Compared to nondrinkers, those who consumed 23.1-46.0 or 46.1-69.0 g ethanol/drinking day on 4-7 drinking days/week had a decreased risk of CKD (multiple-adjusted hazard ratio (HR) 0.62 (0.52-0.74) and 0.76 (0.59-0.97), respectively). The association between the quantity per drinking day and the incidence of CKD was U-shaped among each category of the weekly frequency. HRs within similar categories of quantity per drinking day were lower in the 4-7 drinking days/week group than in the 1-3 drinking days/week group. CONCLUSION: Among middle-aged Japanese men, the people who drank middle-range quantity, specifically who drank 4-7 days/week, had lower risk of CKD than nondrinkers.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Insuficiencia Renal Crónica/epidemiología , Adulto , Tasa de Filtración Glomerular , Encuestas Epidemiológicas , Humanos , Incidencia , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/fisiopatología , Medición de Riesgo
13.
Reprod Med Biol ; 12(4): 179-185, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29699144

RESUMEN

PURPOSE: Current approaches to in vitro maturation (IVM) may result in low efficiency and inadequate quality of the oocytes due to insufficient cytoplasmic maturation. Although positive effects of the cysteamine supplementation in IVM medium for oocyte nuclear maturation or male pronuclear formation have been confirmed, it is still controversial whether the cysteamine addition affects embryo development after IVM. We aimed here to confirm the effect of cysteamine addition into IVM medium for subsequent embryo development in vitro. METHODS: We administered the cysteamine to the IVM culture of rabbit immature oocytes at various concentrations and observed the developmental rate, speed to reach blastocyst stage and cell numbers at the blastocyst stage. RESULTS: Cysteamine supplementation improved developmental rate to blastocyst stage of the IVM oocytes. On the other hand, addition of glutathione (GSH) inhibitor buthionine sulfoximine inhibited GSH accumulation in the oocytes and subsequent embryo development to the blastocyst stage. CONCLUSIONS: Controlling the GSH quantity of IVM oocytes may be an important factor for success of embryo development, and it is quite probable that a cysteamine supplementation can contribute to an increase of GSH content in oocyte.

14.
Biochem Biophys Res Commun ; 417(2): 836-41, 2012 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-22206673

RESUMEN

Mechanical stimulation has been shown to regulate the proliferation and differentiation of stem cells. However, the effects of the mechanical stress on the stemness or related molecular mechanisms have not been well determined. Pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are used as good materials for cell transplantation therapy and research of mammalian development, since they can self-renew infinitely and differentiate into various cell lineages. Here we demonstrated that the mechanical stimulation to human iPS cells altered alignment of actin fibers and expressions of the pluripotent related genes Nanog, POU5f1 and Sox2. In the mechanically stimulated iPS cells, small GTPase Rho was activated and interestingly, AKT phosphorylation was decreased. Inhibition of Rho-associated kinase ROCK recovered the AKT phosphorylation and the gene expressions. These results clearly suggested that the Rho/ROCK is a potent primary effector of mechanical stress in the pluripotent stem cells and it participates to pluripotency-related signaling cascades as an upper stream regulator.


Asunto(s)
Regulación de la Expresión Génica , Células Madre Pluripotentes Inducidas/fisiología , Mecanotransducción Celular/genética , Quinasas Asociadas a rho/metabolismo , Células Cultivadas , Proteínas de Homeodominio/genética , Humanos , Células Madre Pluripotentes Inducidas/enzimología , Proteína Homeótica Nanog , Factor 3 de Transcripción de Unión a Octámeros/genética , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Transcripción SOXB1/genética , Resistencia a la Tracción , Quinasas Asociadas a rho/genética
15.
Inflamm Res ; 61(10): 1093-100, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22688963

RESUMEN

OBJECTIVE: Excessive mechanical stress on the cartilage causes the degradation of the matrix, leading to the osteoarthritis (OA). Matrix metalloproteinases 13 (MMP13) is a major catalytic enzyme in OA and p38 plays an important role in its induction. However, precise pathway inducing p38 activation has not been elucidated. We hypothesized here that the small GTPase Rho and its effector ROCK might function in upper part of the mechanical stress-induced matrix degeneration pathway. METHODS: Bovine metacarpal phalangeal articular cartilage explants were loaded with 1 MPa dynamic compression for 6 h with or without a ROCK specific inhibitor Y27632 or/and a p38 specific inhibitor SB202190. Then p38 phosphorylation and MMP13 expression were assessed by western blot or/and quantitative RT-PCR. Rho-activity was measured by pull-down assay using glutathione S-transferase fusion protein of Rho binding domain. RESULTS: Cyclic compression caused Rho activation, p38 phosphorylation and MMP13 expression. Both Y27632 and SB202190 were found to block the mechanical stress-enhanced p38 phosphorylation and subsequent MMP13 expression. CONCLUSIONS: The present results show that p38 phosphorylation and MMP13 expression are regulated by Rho/ROCK activation, and support the potential novel pathway that Rho/ROCK is in the upper part of the mechanical stress-induced matrix degeneration cascade in cartilage comprised of p38 and MMP13.


Asunto(s)
Cartílago/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Estrés Mecánico , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Quinasas Asociadas a rho/metabolismo , Amidas/farmacología , Animales , Bovinos , Células Cultivadas , Condrocitos/metabolismo , Inhibidores Enzimáticos/farmacología , Imidazoles/farmacología , Fosforilación , Piridinas/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Quinasas Asociadas a rho/antagonistas & inhibidores
16.
J Orthop Sci ; 17(1): 25-38, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22045450

RESUMEN

BACKGROUND: The Japanese Orthopaedic Association Hip Score is widely used in Japan, but this tool is designed to reflect the viewpoint of health-care providers rather than that of patients. In gauging the effect of medical therapies in addition to clinical results, it is necessary to assess quality of life (QOL) from the viewpoint of patients. However, there is no tool evaluating QOL for Japanese patients with hip-joint disease. METHODS: With the aim of more accurately classifying QOL for Japanese patients with hip-joint disease, we prepared a questionnaire with 58 items for the survey derived from 464 opinions obtained from approximately 100 Japanese patients with hip-joint disease and previously devised evaluation criteria. In the survey, we collected information on 501 cases, and 402 were subjected to factor analysis. From this, we formulated three categories-movement, mental, and pain-each comprising 7 items, for a total of 21 items to be used as evaluation criteria for hip-joint function. RESULTS: The Cronbach's α coefficients for the three categories were 0.93, 0.93, and 0.95, respectively, indicating the high reliability of the evaluation criteria. The 21 items included some related to the Asian lifestyle, such as use of a Japanese-style toilet and rising from the floor, which are not included in other evaluation tools. CONCLUSIONS: This self-administered questionnaire may become a useful tool in the evaluation of not only Japanese patients, but also of members of other ethnic groups who engage in deep flexion of the hip joint during daily activities.


Asunto(s)
Articulación de la Cadera , Artropatías , Procedimientos Ortopédicos , Ortopedia , Evaluación de Resultado en la Atención de Salud , Sociedades Médicas , Encuestas y Cuestionarios , Femenino , Humanos , Japón , Artropatías/terapia , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos
17.
Prog Rehabil Med ; 7: 20220027, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35633758

RESUMEN

Objectives: Advances in cancer treatment have led to extended survival, and, as a result, the number of patients with bone metastases is increasing. Activities of daily living (ADL) decrease with bone metastasis and the need for rehabilitation is increasing. This study examined the effects of rehabilitation in patients with bone metastases. Methods: We retrospectively reviewed data of cancer patients with bone metastasis who received rehabilitation between 2016 and 2018. Efficacy of rehabilitation was evaluated in 92 patients as the change in the Functional Independence Measure (FIM) score divided by rehabilitation days (FIM change/day) and assessed by different metastatic sites. Results: Overall FIM scores significantly improved after rehabilitation. Moreover, FIM change/day improved in patients with pelvic metastases (n=44) more than in patients with other metastatic sites (n=48) (P=0.015). In FIM motor components, improvements in toilet, tub/shower, walk/wheelchair, and stairs were significantly greater in patients with pelvic metastasis than in those with other metastasis sites. Conclusions: Rehabilitation improved ADL status to a greater extent in patients with pelvic metastases than in those with other metastasis sites. Patients with pelvic metastases may fear fractures, limiting their ADL, but rehabilitation could eliminate this fear and improve FIM.

18.
Am J Nephrol ; 34(4): 324-9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21849773

RESUMEN

BACKGROUND/AIMS: No prospective studies have estimated the association between white blood cell (WBC) count and the risk of proteinuria. We prospectively examined the relationships of WBC count, as a marker of inflammation, with two outcomes: proteinuria and low estimated glomerular filtration rate (eGFR). METHODS: We enrolled 10,008 Japanese men aged 40-55 years who had neither proteinuria nor low eGFR and were not taking antihypertensive medications at entry. Proteinuria was defined as 1+ or higher on urine dipstick. Low eGFR was defined if eGFR was <60 ml/min/1.73 m(2). RESULTS: During the 49,644 person-years of follow-up, 1,557 cases of proteinuria were confirmed. After adjusting for age, body mass index, fasting plasma glucose, systolic blood pressure, diastolic blood pressure, antidiabetic medications, alcohol consumption, smoking, regular leisure-time physical activity and eGFR, the highest quintile (≥7.51 × 10(3)/µl) of WBC count was independently associated with an increased risk of incidence of proteinuria [HR: 1.45 (95% CI: 1.23-1.73)] compared with the lowest quintile (≤4.80 × 10(3)/µl). On the other hand, during 52,833 person-years, we confirmed 439 cases of low eGFR. In multivariate models, there was no association between WBC count and low eGFR. CONCLUSION: Elevated WBC count was independently associated with an increased risk of proteinuria, but not low eGFR.


Asunto(s)
Tasa de Filtración Glomerular , Leucocitos/citología , Proteinuria/patología , Adulto , Recuento de Células Sanguíneas , Glucemia/metabolismo , Presión Sanguínea , Índice de Masa Corporal , Humanos , Japón , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Proteinuria/metabolismo , Resultado del Tratamiento
19.
Respiration ; 82(6): 492-500, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21474913

RESUMEN

BACKGROUND: Exertional dyspnea is the primary symptom that limits exercise in patients with chronic obstructive pulmonary disease (COPD). It is unknown which activated brain area is associated with this symptom in COPD patients. OBJECTIVES: To investigate the activation of cortical areas associated with dyspnea during exercise in COPD patients. METHODS: COPD patients (n = 10) and age-matched controls (n = 10) performed mild-intensity constant work rate cycle exercise (40% of their symptom-limited peak work rates) for 10 min, while cerebral hemodynamics and oxygenation were measured by near-infrared spectroscopy (NIRS). Ventilatory responses (breathing pattern and pulmonary gas exchange) and Borg scale ratings of dyspnea and leg fatigue were measured during exercise. Three NIRS probes were placed over the prefrontal and temporoparietal cortical regions of the subjects' heads. Changes in cortical oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), and total hemoglobin (total Hb) concentrations from baseline recordings were measured. Increased oxy-Hb (oxygenation) was assumed to reflect cortical activation. RESULTS: Oxy-Hb concentration was significantly increased in the prefrontal region during exercise in both groups but not in the temporoparietal regions. The change in prefrontal oxy-Hb concentration of COPD patients was not different from that of controls. Dyspnea scores were positively correlated with changes in oxy-Hb concentrations of the prefrontal regions in both groups. Multivariate analysis showed that oxy-Hb concentration in the prefrontal region was the best predictor of dyspnea in both groups. CONCLUSIONS: Exertional dyspnea was related to activation (oxygenation) of the prefrontal cortex in COPD patients and control subjects.


Asunto(s)
Disnea/fisiopatología , Tolerancia al Ejercicio , Corteza Prefrontal/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Intercambio Gaseoso Pulmonar , Espectroscopía Infrarroja Corta , Anciano , Estudios de Casos y Controles , Disnea/etiología , Disnea/metabolismo , Prueba de Esfuerzo/métodos , Hemoglobinas/metabolismo , Humanos , Masculino , Oxihemoglobinas/metabolismo , Valor Predictivo de las Pruebas , Corteza Prefrontal/irrigación sanguínea , Corteza Prefrontal/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Valores de Referencia
20.
Respir Care ; 66(9): 1458-1468, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34230214

RESUMEN

BACKGROUND: A recent paper reported that low muscle mass in the erector spinae muscles (ESM) was strongly associated with poor prognosis and declining muscle mass over time in subjects with COPD. However, effects of pulmonary rehabilitation (PR), if any, on ESM mass have not been reported. We hypothesized that PR reduces the annual decline in ESM mass. METHODS: This was a retrospective cohort study. Thirty-nine subjects with COPD who received PR and underwent chest computed tomography before and after PR were evaluated (rehabilitation group). We also evaluated 39 age-matched subjects with COPD who did not receive PR (nonrehabilitation group). Data were collected from August 2010 until March 2020 in both groups. The ESM cross-sectional area (ESMCSA) was measured using axial computed tomography images, and annual changes were calculated. The 6-min walk distance (6MWD) was measured before and after PR; the minimum clinically important difference was defined as 30 m. RESULTS: ESMCSA declined in the nonrehabilitation group over time (-116.0 ± 141.2 mm2/y) but increased in the PR group (51.0 ± 95.3 mm2/y; P < .001). The annual increase in ESMCSA was significantly higher among subjects with an increase in 6MWD that exceeded the minimum clinically important difference compared with nonresponders in the rehabilitation group. The annual change in ESMCSA was negatively correlated with comorbidity index, and triple therapy (long-acting ß2-agonist/long-acting muscarinic antagonist/inhaled corticosteroid) had a favorable effect on annual change in ESMCSA. Multiple regression analysis revealed that only PR was an independent factor for annual change in ESMCSA. CONCLUSIONS: ESM mass was shown to decline yearly in subjects with COPD. The annual decline in muscle mass was reduced by PR.


Asunto(s)
Diferencia Mínima Clínicamente Importante , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Músculos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
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