RESUMEN
The purpose of this study was to develop and evaluate a navigation program for patients with thyroid cancer. The navigation program was developed following an analysis of the unmet needs of patients who underwent surgery for thyroid cancer. Ninety-nine patients in the control group received usual care, and 95 in the navigation group were managed with a navigation program during the perioperative period. The effectiveness of the navigation program was assessed by administering a questionnaire to both groups. Overall satisfaction scores were significantly higher in the navigation than in the control group (p = .025), as were satisfaction scores on the continuity of information (p < .001), the continuity of management (p = .002), the continuity of relationships with healthcare providers (p<.001), and patient empowerment (p < .001). The newly developed navigation program for patients with thyroid cancer was effective in raising satisfaction levels and in actively managing the disease during the perioperative period.
Asunto(s)
Navegación de Pacientes/métodos , Atención Perioperativa/métodos , Neoplasias de la Tiroides/cirugía , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Continuidad de la Atención al Paciente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Satisfacción del Paciente , Evaluación de Programas y Proyectos de Salud , Adulto JovenRESUMEN
OBJECTIVE: Resveratrol is a naturally occurring polyphenol, which possesses chemotherapeutic potential through its ability to trigger apoptosis. The objective of this study was to investigate the major determinant for the apoptotic cell death induction by resveratrol in fibroblast-like synoviocytes (FLS) derived from patients with RA. METHODS: The effect of resveratrol on apoptotic cell death was quantified in a population of subG1 in RA FLS by flow cytometry. The underlying signalling mechanism for apoptotic death was examined by analysing mitochondrial membrane potential, activation of the caspase cascade and translocation of Bid. RESULTS: We show that activation of caspase-8 is essential for triggering resveratrol-induced apoptotic signalling via the involvement of the mitochondrial pathway in RA FLS. Our findings also suggest that this enhanced apoptosis caused by resveratrol occurred in RA FLS irrespective of p53 status. Exposure to resveratrol caused extensive apoptotic cell death, along with a caspase-dependent (activation of caspase-9 and -3, poly ADPribose polymerase (PARP) cleavage and mitochondrial cytochrome c release) or caspase-independent [translocation of apoptosis-inducing factor (AIF) to the nucleus] signalling pathway. Analysis of upstream signalling events affected by resveratrol revealed that the activated caspase-8 triggered mitochondrial apoptotic events by inducing Bid cleavage without any alteration in the levels of Bax, Bcl-xL or Bcl2. The caspase-8 inhibitor or over-expression of crmA abrogated cell death induced by resveratrol and prevented processing of the downstream cascade. CONCLUSION: The results suggest that resveratrol causes activation of caspase-8, which in turn results in modulation of mitochondrial apoptotic machinery to promote apoptosis of RA FLS.
Asunto(s)
Factor Inductor de la Apoptosis/metabolismo , Apoptosis/efectos de los fármacos , Artritis Reumatoide/fisiopatología , Caspasa 8/metabolismo , Estilbenos/farmacología , Factor Inductor de la Apoptosis/efectos de los fármacos , Artritis Reumatoide/metabolismo , Caspasa 8/efectos de los fármacos , Células Cultivadas , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Humanos , Potenciales de la Membrana , Mitocondrias/fisiología , Probabilidad , Resveratrol , Sensibilidad y Especificidad , Membrana Sinovial/citología , Membrana Sinovial/efectos de los fármacosRESUMEN
AimsThe aims of this study were to investigate the longitudinal change in lateral rectus (LR) muscle insertion after recession surgery, and to evaluate a relationship between insertion distance and postoperative amount of deviation.MethodsWe recruited 31 patients who underwent primary LR recession surgery with normal anterior segment structures. An AS-OCT scan of the LR muscle was performed at every visit. Data on sex, age, degree of deviation (prism diopter), and spur-LR insertion distance using AS-OCT were collected at preoperatively and postoperative months 1, 3, and 6. Spur-LR insertion was defined as the shortest distance between the insertion of the LR muscle and the scleral spur was measured using the caliper function in the AS-OCT software.ResultsThe mean distance of spur-LR insertion measured with AS-OCT was 5.5±0.7 mm preoperatively, and 11.1±0.9 mm at 1 month, 11.5±0.8 mm at 3 months, and 11.0±0.7 mm at 6 months postoperatively. There were significant differences in spur-LR insertion between postoperative 1 and 3 months, and between 3 and 6 months (generalized estimating equation, all P<0.001). The overall spur-LR insertion measurement has a significantly negative correlation with postoperative amount of deviation (Pearson's correlation, P=0.035, r=-0.218).ConclusionsAS-OCT is a useful instrument for understanding postoperative changes in EOM after tissue swelling subsides.
Asunto(s)
Segmento Anterior del Ojo/diagnóstico por imagen , Movimientos Oculares/fisiología , Músculos Oculomotores/patología , Procedimientos Quirúrgicos Oftalmológicos/métodos , Esclerótica/cirugía , Estrabismo/cirugía , Tomografía de Coherencia Óptica/métodos , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Músculos Oculomotores/cirugía , Periodo Posoperatorio , Esclerótica/diagnóstico por imagen , Estrabismo/diagnóstico , Estrabismo/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
PurposeThe purpose of this study is to describe the clinical characteristics and treatment results of medial rectus muscle (MR) transection incurred during endoscopic sinus surgery.MethodsThis retrospective study included 16 patients with MR transection incurred during endoscopic sinus surgery between 1994 and 2015. The operative notes of the surgical procedure, the pattern of strabismus, the type of muscle injury, the type of corrective strabismus surgery, and the surgical outcomes were reviewed.ResultsNine patients had partial resection of MR and seven patients had complete transection of MR, resulting from an injury incurred during endoscopic sinus surgery. Three of the nine patients with partial resection injury were initially diagnosed as complete resection and subsequently re-diagnosed as partial resection in a review of the images during this study. Five of the nine patients with partial MR resection underwent only simple recession/resection surgery. Patients with complete MR transection underwent muscle transposition or globe fixation surgeries and often multiple operations were required.ConclusionsThe results of this study showed that the treatment strategies could vary depending on the nature of muscle injury. In cases with complete transection, muscle transposition or globe fixation surgeries are often required, with multiple operations. However, partial muscle resection with only simple recession/resection surgery shows a favorable outcome in many cases. The use of proper imaging techniques, a thorough review of the images with various planes, and close follow-up are important for determining the nature of the muscle injury.
Asunto(s)
Lesiones Oculares/etiología , Procedimientos Quírurgicos Nasales/efectos adversos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Músculos Oculomotores/lesiones , Senos Paranasales/cirugía , Adulto , Humanos , Enfermedad Iatrogénica , Imagen por Resonancia Magnética , Persona de Mediana Edad , Músculos Oculomotores/trasplante , Estudios Retrospectivos , Estrabismo/etiología , Estrabismo/cirugía , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
PURPOSE: To compare retinal nerve fiber layer (RNFL) thickness profiles between preterm and full-term children and to investigate factors affecting the RNFL distribution in preterm children. METHODS: We performed Spectral domain optical coherence tomography (SD-OCT) peripapillary RNFL circular scan centered on the optic disc in 50 premature and 58 full-term children. RNFL thickness profiles were compared between preterm and full-term children using a linear regression model. Among preterm patients in this study, 20 patients previously received laser treatment for severe retinopathy of prematurity (ROP). RESULTS: Global average, nasal, and superior disc RNFL thickness profiles were significantly smaller in preterm children (92.70±16.57 µm, 56.02±17.04 µm, and 108.74±27.36 µm, respectively) compared with full-term children (101.63±9.21 µm, P=0.006, 69.14±14.15 µm, P<0.001, and superior, 129.11±18.14 µm, P<0.001, respectively). Multivariable analysis revealed that ROP stage was inversely correlated with nasal RNFL thickness (P=0.010). CONCLUSIONS: Our SD-OCT data demonstrate decreased global average, nasal, and superior disc RNFL thicknesses in preterm children. ROP stage was inversely correlated with nasal RNFL thickness. Further studies are needed to better understand the association between these structural changes and visual functions in preterm children.
Asunto(s)
Fibras Nerviosas/patología , Células Ganglionares de la Retina/patología , Retinopatía de la Prematuridad/clasificación , Adolescente , Peso al Nacer , Niño , Preescolar , Femenino , Edad Gestacional , Humanos , Coagulación con Láser , Masculino , Tamaño de los Órganos , Nacimiento Prematuro , Estudios Prospectivos , Retinopatía de la Prematuridad/cirugía , Nacimiento a Término , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
AIMS: To investigate the influence of preterm birth on the optic disc and retinal vessels by measurements of cup-to-disc (C/D) ratio and arteriole-to-venule (A/V) ratio. METHODS: Eighty-three eyes of 42 preterm births were included. In the age- and sex-matched control group, 83 eyes of 42 full-term births were used. Fundus color photographs were taken. ImageJ software was used to calculate C/D and A/V ratios from the fundus images. RESULTS: Fundus photographs were taken at 8.01 ± 2.22 years of age for the preterm group and 8.01 ± 2.13 years of age for the control group. The mean gestational age of the preterm group was 27(4)/7 weeks (range, 24-34 weeks). The preterm group had significantly larger C/D ratio and smaller A/V ratio (mean ± standard deviation: 0.46 ± 0.12 and 0.59 ± 0.08, respectively) than the control group (0.36 ± 0.07 and 0.68 ± 0.07, respectively) after spherical equivalent refractive error was adjusted. CONCLUSIONS: Preterm birth is significantly associated with larger C/D ratio and smaller A/V ratio. These findings show the effect of preterm birth on the development of optic disc and retinal vessel development.
Asunto(s)
Técnicas de Diagnóstico Oftalmológico , Recien Nacido Prematuro , Disco Óptico/anatomía & histología , Vasos Retinianos/anatomía & histología , Retinopatía de la Prematuridad/diagnóstico , Arteriolas/anatomía & histología , Estudios de Casos y Controles , Femenino , Fondo de Ojo , Edad Gestacional , Humanos , Procesamiento de Imagen Asistido por Computador , Recién Nacido , Masculino , Fotograbar , Errores de Refracción , Estudios Retrospectivos , Vénulas/anatomía & histologíaRESUMEN
Protein tyrosine phosphorylation is regulated by protein tyrosine kinase and protein tyrosine phosphatase activities. These two counteracting proteins are implicated in cell growth and transformation. Using polymerase chain reaction with degenerate primers, we have identified a novel mouse protein tyrosine phosphatase (PTP). This cDNA contains a single open reading frame of the predicted 926 amino acids. Those predicted amino acids showed significant identity with human megakaryocyte protein-tyrosine phosphatase by 91% in nucleotide sequences and 94% in amino acid sequences. We have identified that expression of this PTP is highly enriched in the testis in mouse and human and has been termed here as a 'testis-enriched phosphatase' (TEP). Northern analysis detected two mRNA species of 3.7 and 3.2kb for this PTP in mouse testis and the expression of TEP is regulated during development. The recombinant phosphatase domain possesses protein tyrosine phosphatase activity when expressed in Escherichia coli. Immunohistochemical analysis of the cellular localization of TEP on mouse testis sections showed that this PTP is specifically expressed in spermatocytes and spermatids within seminiferous tubules, suggesting an important role in spermatogenesis.
Asunto(s)
Megacariocitos/enzimología , Proteínas Tirosina Fosfatasas/genética , Testículo/enzimología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Clonación Molecular , ADN Complementario/química , ADN Complementario/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Megacariocitos/citología , Ratones , Datos de Secuencia Molecular , Proteínas Tirosina Fosfatasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Testículo/crecimiento & desarrollo , Distribución TisularRESUMEN
Succinic semialdehyde reductase (SSR) that catalyzes the reduction of succinic semialdehyde (SSA) to gamma-hydroxybutyrate (GHB) has been identified as one of the NADPH-dependent aldehyde reductases. Reduction of SSA to GHB strongly supports the proposal that GHB biosynthesis may be an important step in the GABA shunt. It is pharmacologically significant in anesthesia, evoking the state of sleep, and an increase in brain dopamine level. Monoclonal antibodies against bovine brain succinic semialdehyde reductase were produced. Using the anti-succinic semialdehyde reductase antibodies, we investigated the distribution of brain succinic semialdehyde reductase in rat brain. The brain tissues were sectioned with a basis on the rat brain atlas of Paxinos and were stained by the immunoperoxidase staining method using monoclonal antibodies. In the section of the frontal lobe, immunoreactive cells were observed in the lateral septal area, the ventral pallidum, which belongs to the substantia innominata. We could observe immunoreactive cells in the reticular thalamic nucleus, which is closely related with 'sleeping', the basal nuclei of Meynert, which is associated with Alzheimer's disease, and hypothalamic nuclei. Immunoreactive cells were also shown in raphe nuclei or the reticular formation of the midbrain, cerebellum, and inferior olivary nuclei of the medulla oblongata. Succinic semialdehyde reductase-immunoreactive cells were distributed extensively in rat brain, especially immunoreactive cells were strongly observed in the areas associated with the limbic system and reticular formation.
Asunto(s)
Encéfalo/enzimología , Hidroxibutirato Deshidrogenasa/metabolismo , Animales , Anticuerpos Monoclonales , Encéfalo/anatomía & histología , Bovinos , Hidroxibutirato Deshidrogenasa/inmunología , Técnicas para Inmunoenzimas , Sistema Límbico/enzimología , Microscopía Inmunoelectrónica , Ratas , Formación Reticular/enzimología , Oxibato de Sodio/metabolismo , Distribución Tisular , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Peripheral nerve injury often induces sympathetic nerve fiber sprouting in the dorsal root ganglion (DRG) and injured nerve. Presently, the underlying mechanism and functional significance of the sprouting are unknown. This study was performed to see whether the degree of the sprouting in the DRG was a function of the distance between the DRG and injury site. To this aim, we compared two groups of rats with respect to the sympathetic nerve fibers sprouting in the S1-3 DRG; one group was subjected to unilateral inferior and superior caudal trunk transections at the level between the S3 and S4 spinal nerves (S34 group) and the other group at the levels between the S1 and S2, between S2 and S3 and between S3 and S4 spinal nerves (S123 group). The transections in both groups equally eliminated the inputs from the tail to the S1-3 DRG, but the distance from the S1/S2 DRG to the injury site was different between the two groups. Immunohistochemical staining with tyrosine hydroxylase (TH) antibody of the S1-3 DRG removed from rats a week after the injury revealed that the degree of penetration of TH-positive fibers into the S1 and S2 DRG was much more extensive in the S123 group than in the S34 group, whereas that into the S3 DRG was not significantly different between the two groups. These results suggest that the extent of the sympathetic nerve fiber sprouting in the DRG following peripheral nerve injury is inversely related to the distance between the DRG and injury site.
Asunto(s)
Ganglios Espinales/fisiología , Sistema Nervioso Periférico/lesiones , Sistema Nervioso Simpático/fisiología , Animales , Inmunohistoquímica , Masculino , Ratas , Ratas Sprague-Dawley , TemperaturaRESUMEN
The objective of this study is to explain spatial variations in cardiovascular mortality by sex. Recognizing the interdependence of the various dimensions of the 'ecological complex', it is maintained that spatial variations in cardiovascular mortality by sex and the sex differentials in cardiovascular mortality are the consequences of environmental, sustenance organization, health technology, and demographic factors. The test of the model is based on U.S. county level cardiovascular mortality data for ages 25-65 for the period 1970-1980. The most distinctive feature of the results is that environment has the greatest impact on sex differentials in cardiovascular mortality followed by sustenance organization. In this regard, socioeconomic status is shown to be the single most important variable in explaining cardiovascular mortality rates for both sexes in most community types. The effect of health technology is not significant, and increased availability of health manpower and facilities are often found in conjunction with higher rates of cardiovascular mortality for both sexes. The results of this study confirm the importance of programs directed toward altering the basic environment and sustenance organization structures of communities rather than other ecological components such as health technology.
Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Ecología , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Ciencia del Laboratorio Clínico , Persona de Mediana Edad , Factores Sexuales , Factores Socioeconómicos , Estados UnidosRESUMEN
Animal models for human chronic pain syndromes have been developed and widely used for pain research. One of these neuropathic pain models by Kim and Chung (1992) has many advantages for operation and pain elicitation. In this neuropathic model we have examined the c-fos protein, substance P, CGRP immunoreactivity in dorsal root ganglia and dorsal horn. 50 Sprague-Dawley rats were used for this study. L5 and L6 spinal nerves were ligated tightly to produce the neuropathic pain model. After 2, 4, 8, 16, and 24 hours and 1 week of surgery, rats were anesthetized and sacrificed by perfusion. After confirmation of the roots transected by the surgery, the L5 and L6 dorsal root ganglions and spinal cord were removed and processed for immunohistochemistry. All tissue sections were immunohistochemically stained for substance P, CGRP and c-fos using the peroxidase-antiperoxidase (PAP) method. The number of immunostained substance P and CGRP dorsal root ganglion cells and c-fos immunoreactive dorsal horn cells were counted and analyzed statistically with Mann-Whitney U test. The results are as follows. The number of c-fos protein immunoreactive neurons in the superficial layer of dorsal horn were increased markedly 2 hours after operation, and gradually decreased to normal level 1 week after operation. The number of c-fos protein immunoreactive neurons in the deep layer of the dorsal horn gradually increased to a peak 24 hours after operation, then decreased to the normal level 1 week after operation. The number of substance P and CGRP immunoreactive L5 and L6 dorsal root ganglion neurons were decreased markedly 1 week after the pain model operation. In conclusion, after neuropathic pain model operation, c-fos proteins were immediately expressed in the superficial layer of spinal dorsal horn, thereafter c-fos proteins in the deep layer of spinal dorsal horn were expressed. CGRP and substance P immunoreactive neurons in DRG were decreased markedly 1 week after neuropathic pain model operation. These decrements do not coincide with the other chronic pain models, which show great increases in these pain transmitting substances. Therefore, the relationship between pain and c-fos, SP and CGRP should be investigated further.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/análisis , Ganglios Espinales/química , Neurotransmisores/análisis , Dolor/metabolismo , Enfermedades del Sistema Nervioso Periférico/metabolismo , Proteínas Proto-Oncogénicas c-fos/análisis , Médula Espinal/química , Sustancia P/análisis , Animales , Inmunohistoquímica , Ratas , Ratas Sprague-DawleyRESUMEN
Hydrogen peroxide is considered to be a dose- and time-dependent mediator in apoptotic and necrotic death. In this study, we examined the signaling of the E6 and E7 proteins with respect to apoptosis or necrosis after H2O2 injury using an in vitro model with overexpressed E6 or E7 genes. For this purpose, the E6 and E7 gene expressing astrocytes were exposed to 10 micromole and 200 micromole H2O2 solutions. Twenty- four hours after treatment with the lower dosage(10 micromole H2O2), control, E6-expressing cells suffered about 45% injury and LXSN-expressing cells decreased by 67% as assessed by LDH release. However, E7-expressing cells showed less injury, resulting in 20-30% of LDH release. Astrocytes expressing E6, E7, LXSN and mock-infected cells showed a typical apoptotic death pattern on the DNA gel after treatment with a low-dose of H2O2 (10 micromole), however they died from necrotic death after a high-dose (200 micromole) H2O2. Overexpression of HPV-E7 genes protected the cells from apoptotic death after a low-dose of H2O2 and from necrotic death after a high-dose of H2O2, while the overexpression of E6 genes from the necrotic death. E7 expressing astrocytes showed higher catalase activity and the levels of E2F protein surged more than 100-folds compared with the control astrocytes. We believe that the activity of E7 protein to protect astrocytes from H2O2 injury was at least partly due to increased catalase, a scavenger protein.
Asunto(s)
Apoptosis/fisiología , Astrocitos/efectos de los fármacos , Astrocitos/fisiología , Peróxido de Hidrógeno/farmacología , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/fisiología , Oxidantes/farmacología , Animales , Astrocitos/patología , Células Cultivadas , Ratones , Necrosis , Proteínas E7 de Papillomavirus , Transducción de Señal/fisiologíaRESUMEN
Metabolic diseases and cardiovascular disease (CVD), the incidence of which is currently increasing in Korea, can be managed well with dietary education and modification. However, it has yet to be established whether nurses have sufficient knowledge to impart appropriate nutritional counseling to patients with these diseases. Our study involved 506 nurses working at Asan Medical Center, Samsung Medical Center, and Seoul National University Hospital between March and May, 2006. The questionnaire was comprised of 42 diet-related questions pertaining to diabetes, obesity, and CVD. Nurses' correct-response rate for overall nutritional knowledge was worse than reported in Western countries (58.4%), and particularly so with regard to obesity and CVD. Although many nurses were aware of the therapeutic aspects of nutrients in relation to CVD, most of them had limited knowledge about low-cholesterol diets and sources of water-soluble fiber, fatty acids and the specific food items that prevent CVD. Our results suggest that there is an urgent need to update the contents of nutrition education for nurses to reflect the current changes in the Korean diet and the increasing incidence of metabolic diseases and CVD.
Asunto(s)
Enfermedades Cardiovasculares/dietoterapia , Competencia Clínica/estadística & datos numéricos , Consejo Dirigido/métodos , Conocimientos, Actitudes y Práctica en Salud , Enfermería/estadística & datos numéricos , Análisis de Varianza , Enfermedades Cardiovasculares/enfermería , Enfermedades Cardiovasculares/prevención & control , Competencia Clínica/normas , Diabetes Mellitus/dietoterapia , Consejo Dirigido/normas , Promoción de la Salud/métodos , Humanos , Enfermería/normas , Encuestas Nutricionales , Obesidad/dietoterapia , República de Corea , Encuestas y CuestionariosAsunto(s)
Enfermedades de la Coroides/epidemiología , Adolescente , Adulto , Niño , Preescolar , Enfermedades de la Coroides/complicaciones , Enfermedades de la Coroides/diagnóstico , Dilatación Patológica/diagnóstico , Dilatación Patológica/epidemiología , Lesiones Oculares/complicaciones , Femenino , Humanos , Masculino , Prevalencia , Enfermedades de la Retina/complicaciones , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
Nerve growth factor (NGF) can augment transmitter release in sensory neurons by acutely sensitizing sensory neurons and by increasing the expression of calcitonin gene-related peptide (CGRP) over time. The current study examined the intracellular signaling pathways that mediate these two temporally distinct effects of NGF to augment CGRP release from sensory neurons. Growing sensory neurons in 30 or 100 ng/mL of NGF for 7 days increases CGRP content and this increase augments the amount of CGRP that is released by high extracellular potassium. Overexpressing a dominant negative Ras, Ras(17N) or treatment with a farnesyltransferase inhibitor attenuates the NGF-induced increase in CGRP content. Conversely, overexpressing a constitutively active Ras augments the NGF-induced increase in content of CGRP. Inhibiting mitogen activated protein kinase (MEK) activity also blocks the ability of NGF to increase CGRP expression. In contrast to the ability of chronic NGF to increase peptide content, acute exposure of sensory neurons to 100 ng/mL NGF augments capsaicin-evoked release of CGRP without affecting the content of CGRP. This sensitizing action of NGF is not affected by inhibiting Ras, MEK, or PI3 kinases. In contrast, the NGF-induced increase in capsaicin-evoked release of CGRP is blocked by the protein kinase C (PKC) inhibitor, BIM and the Src family kinases inhibitor, PP2. These data demonstrate that different signaling pathways mediate the alterations in expression of CGRP by chronic NGF and the acute actions of the neurotrophin to augment capsaicin-evoked release of CGRP in the absence of a change in the content of the peptide.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/genética , Péptido Relacionado con Gen de Calcitonina/metabolismo , Factor de Crecimiento Nervioso/fisiología , Nociceptores/metabolismo , Células Receptoras Sensoriales/metabolismo , Transducción de Señal/fisiología , Regulación hacia Arriba/fisiología , Animales , Péptido Relacionado con Gen de Calcitonina/biosíntesis , Células Cultivadas , Ganglios Espinales/metabolismo , Ganglios Espinales/fisiología , Masculino , Factor de Crecimiento Nervioso/metabolismo , Nociceptores/fisiología , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Células Receptoras Sensoriales/fisiología , Transducción de Señal/genética , Regulación hacia Arriba/genéticaRESUMEN
The zinc-finger protein A20 has crucial physiological functions as a dual inhibitor of nuclear factor-κB (NF-κB) activation and apoptosis in tumor necrosis factor (TNF) receptor 1 signaling pathway. Although the molecular basis for the anti-NF-κB function of A20 has been well elucidated, the anti-apoptotic function of A20 is largely unknown. Here, we report a novel mechanism underlying the anti-apoptotic function of A20: A20 blocks TNF-induced apoptosis through suppression of c-jun N-terminal kinase (JNK) by targeting apoptosis signal-regulating kinase1 (ASK1). First, the ectopic expression of A20 drastically inhibits TNF-induced JNK activation and apoptosis in multiple cell types including those deficient of NF-κB activation. Unexpectedly, the blunting effect of A20 on TNF-induced JNK activation is not mediated by affecting the TNFR1 signaling complex formation. Instead, A20 interacts with ASK1, an important MAPKK kinase in the JNK signaling cascade. More importantly, overexpression of wild-type A20, but not of mutant A20 (ZnF4; C624A, C627A), promotes degradation of the ASK1 through the ubiquitin-proteasome system. Taken together, the results from this study reveal a novel anti-apoptotic mechanism of A20 in TNF signaling pathway: A20 binds to ASK1 and mediates ASK1 degradation, leading to suppression of JNK activation and eventually blockage of apoptosis.
Asunto(s)
Apoptosis , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , MAP Quinasa Quinasa Quinasa 5/metabolismo , Proteínas Nucleares/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Línea Celular Tumoral , Proteínas de Unión al ADN , Humanos , FN-kappa B/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Transducción de Señal , Factor 2 Asociado a Receptor de TNF/metabolismo , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa , UbiquitinaciónAsunto(s)
Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/fisiopatología , Trasplante de Riñón/patología , Capilares/patología , Complemento C3/análisis , Creatinina/sangre , Familia , Estudios de Seguimiento , Mesangio Glomerular/irrigación sanguínea , Mesangio Glomerular/patología , Glomerulonefritis por IGA/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Supervivencia de Injerto , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Fallo Renal Crónico/cirugía , Trasplante de Riñón/fisiología , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Complicaciones Posoperatorias , Recurrencia , Factores de Tiempo , Donantes de TejidosAsunto(s)
Encéfalo/enzimología , L-Lactato Deshidrogenasa/análisis , Animales , Isoenzimas , Conejos , Distribución TisularRESUMEN
PIP: Park provides information on the extent and nature of geographic variations of sex mortality differentials from all causes. He also discusses the relationship between environmental conditions and mortality. The mortality database is derived from the 1982 Vital Statistics. The population database is derived from the 1980 Population and Housing Census Report. For socio-environmental indicators, data are derived from various censuses conducted in Korea circa 1980 as reported in the 1980 Population and Census Report, the 1983 Social Indicators in Korea, and the 1981 Year Book of Labour Statistics. In this study, deaths from all causes in Korea circa 1980 are included, and provinces are used as the unit of analysis. Death rates are age adjusted by the direct method using the age distribution of the 1980 Korea Complete Enumeration Population as the standard. As a measure of sex mortality differentials, the ratio of male to female age adjusted death rates is used. Standard errors of mortality rates are calculated to determine how confident one can be that the rate of a particular province differs from the rate of Korea as a whole. The author found that the mortality rates in Korea are not randomly distributed geographically. Male and female death rates usually coincide spatially. However, in Jeju and Chungnam, mortality patterns are significantly different by sex. This suggests that explanatory variables for sex differentials in mortality are strongly tied to socioenvironmental conditions of the area rather than biological conditions of each sex. In most provinces, male children have a higher risk of death than female children, which confirms that sex differentials in childhood mortality reflect innate biological sex differences. However, in some predominantly rural provinces, females have a higher risk of death than male children, suggesting that socioenvironmental effects far exceed biological influences. The factor most commonly mentioned as an influence on sex mortality differentials is the relative socioeconomic status of women and girls. Higher female versus male mortality is attributable to the subordinate position of women and the relative discriminatory parental care of female children. In Korea, mortality differentials over geographic aggregation by the province level suggest that urban areas have lower mortality for both sexes than rural areas. This implies significant differences in lifestyles, quality of physical environment, occupational characteristics, industry distribution, and accessibility to medical services.^ieng