RESUMEN
We developed a steady-state high-density plasma source by applying a hollow cathode to a cascade arc discharge device. The hollow cathode is made of a thermionic material (LaB6) to facilitate plasma production inside it. The cascade arc discharge device with the hollow cathode produced a stationary plasma with an electron density of about 1016 cm-3. It was found that the plasma source produces a strong pressure gradient between the gas feed and the vacuum chamber. The plasma source separated the atmospheric pressure (100 kPa) and a vacuum (100 Pa) when the discharge was performed with an argon gas flow rate of 5.0 l/min and a discharge current of 40 A. An analysis of the pressure gradient along the plasma source showed that the pressure difference between the gas feed and the vacuum chamber can be well described by the Hagen-Poiseuille flow equation, indicating that the viscosity of the neutral gas is the dominant factor for producing this pressure gradient. A potential profile analysis suggested that the plasma was mainly heated within cylindrical channels whose inner diameter was 3 mm. This feature and the results of the pressure ratio analysis indicated that the temperature, and, thus, viscosity, of the neutral gas increased with the increasing number of intermediate electrodes. The discharge characteristics and shape of the hollow cathode are suitable for plasma window applications.
RESUMEN
The purpose of this study was to determine the most sensitive diagnostic test for nerve conduction study (NCS) of the foot for early detection of diabetic polyneuropathy. We compared the sensitivities for diagnosis of sensory polyneuropathy of four different nerve conduction techniques in the same nerves: nerve conduction studies of the medial plantar nerve with surface electrodes using three different techniques and a nerve conduction study of the digital and interdigital nerves of the foot using a near-nerve needle technique. In 25 patients with diabetic polyneuropathy with normal routine NCS, diagnosis of sensory neuropathy was confirmed by medial plantar NCS in 5 patients (20.0%) using Guiloff's method, in 5 patients (20.0%) using Ponsford's method and in 9 patients (36.0%) using Hemmi's method. In digital and interdigital NCS of the foot, a definite neuropathy pattern was observed in 15 patients (60.0%). The most common abnormality was low amplitude of sensory nerve action potential, indicating axonal degeneration. This study demonstrated that digital and interdigital NCS using the near-nerve needle technique is a more sensitive method for detection of early-stage diabetic polyneuropathy.
Asunto(s)
Pie Diabético/diagnóstico , Pie Diabético/fisiopatología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/fisiopatología , Conducción Nerviosa/fisiología , Estimulación Física/métodos , Adulto , Anciano , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agujas , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND PURPOSE: We report decremental responses to repetitive nerve stimulation (RNS) in 11 patients diagnosed with X-linked spinobulbar muscular atrophy (X-SBMA). METHODS: The compound muscle action potential (CMAP) of the right abductor digiti minimi (ADM) and trapezius (TZ) in response to a 3-Hz stimulation of the ulnar nerve at the wrist and accessory nerve at the neck were recorded by surface electrodes. RESULTS: A decremental response to RNS was observed in 90.9% of the TZ muscle and 27.2% in the ADM muscle of patients with X-SBMA. CONCLUSION: These electrophysiological features of X-SBMA are considered to be useful for diagnosis of X-SBMA. Furthermore, the waning phenomena that mostly appeared in the TZ muscle and increment of CMAP in RNS after the exercise also suggest a unique manifestation in X-SBMA.
Asunto(s)
Atrofia Bulboespinal Ligada al X/diagnóstico , Atrofia Bulboespinal Ligada al X/fisiopatología , Estimulación Eléctrica/métodos , Electrodiagnóstico/métodos , Fatiga Muscular/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Caveolins, components of the uncoated invaginations of plasma membrane, regulate signal transduction and vesicular trafflicking. Loss of caveolin-3, resulting from dominant negative mutations of caveolin-3 causes autosomal dominant limb-girdle muscular dystrophy (LGMD) 1C and autosomal dominant rippling muscle disease (AD-RMD). Myostatin, a member of the muscle-specific transforming growth factor (TGF)-beta superfamily, negatively regulates skeletal muscle volume. Herein we review caveolin-3 suppressing of activation of type I myostatin receptor, thereby inhibiting subsequent intracellular signaling. In addition, a mouse model of LGMD1C has shown atrophic myopathy with enhanced myostatin signaling. Myostatin inhibition ameliorates muscular phenotype in the model mouse, accompanied by normalized myostatin signaling. Enhanced myostatin signaling by caveolin-3 mutation in human may contribute to the pathogenesis of LGMD1C. Therefore, myostatin inhibition therapy may be a promising treatment for patients with LGMD1C. More recent studies concerning regulation of TGF-beta superfamily signaling by caveolins have provided new insights into the pathogenesis of several human diseases.
Asunto(s)
Caveolina 3/fisiología , Miostatina/fisiología , Transducción de Señal/fisiología , Animales , Caveolina 3/genética , Caveolina 3/metabolismo , Modelos Animales de Enfermedad , Humanos , Músculo Esquelético/metabolismo , Distrofia Muscular de Cinturas/genética , Distrofia Muscular de Cinturas/metabolismo , Distrofia Muscular de Cinturas/fisiopatología , Distrofia Muscular de Cinturas/terapia , Mutación , Miostatina/antagonistas & inhibidores , Miostatina/metabolismo , Fosforilación , Proteínas Smad/metabolismo , Transcripción Genética/fisiología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
RNA interference (RNAi) offers a novel therapeutic strategy based on the highly specific and efficient silencing of a target gene. Since it relies on small interfering RNAs (siRNAs), a major issue is the delivery of therapeutically active siRNAs into the target tissue/target cells in vivo. For safety reasons, strategies based on vector delivery may be of only limited clinical use. The more desirable approach is to directly apply active siRNAs in vivo. Here, we report the effectiveness of in vivo siRNA delivery into skeletal muscles of normal or diseased mice through nanoparticle formation of chemically unmodified siRNAs with atelocollagen (ATCOL). ATCOL-mediated local application of siRNA targeting myostatin, a negative regulator of skeletal muscle growth, in mouse skeletal muscles or intravenously, caused a marked increase in the muscle mass within a few weeks after application. These results imply that ATCOL-mediated application of siRNAs is a powerful tool for future therapeutic use for diseases including muscular atrophy.
Asunto(s)
Colágeno/genética , Terapia Genética/métodos , Músculo Esquelético/metabolismo , Distrofia Muscular Animal/terapia , ARN Interferente Pequeño/administración & dosificación , Factor de Crecimiento Transformador beta/genética , Animales , Inmunohistoquímica , Inyecciones Intramusculares , Inyecciones Intravenosas , Masculino , Ratones , Ratones Endogámicos mdx , Músculo Esquelético/patología , Distrofia Muscular Animal/metabolismo , Distrofia Muscular Animal/patología , Miostatina , Nanopartículas , Interferencia de ARN , Factor de Crecimiento Transformador beta/análisisRESUMEN
The transforming growth factor-beta (TGF-beta) superfamily includes TGF-betas, activin, myostatin and bone morphogenetic proteins. Misregulation of the activity of TGF-beta family members is involved in pathogenesis of cancer, muscular dystrophy, obesity and bone and tooth remodeling. Natural inhibitors for the TGF-beta superfamily regulate fine-tuning of activity of TGF-beta family in vivo. In addition to natural inhibitors for the TGF-beta family, soluble forms of receptors for the TGF-beta family, blocking monoclonal antibodies and small chemical TGF-beta inhibitors have been developed. In this review, we summarize recent advances in our understanding of inhibitors for the TGF-beta superfamily and their medical applications.
Asunto(s)
Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/metabolismo , Animales , Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Proteínas Morfogenéticas Óseas/metabolismo , Humanos , Enfermedades Musculares/tratamiento farmacológico , Enfermedades Musculares/metabolismo , Miostatina , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Unión Proteica , Factor de Crecimiento Transformador beta/clasificaciónRESUMEN
The authors performed nerve conduction studies in nine PARK2 and eight idiopathic Parkinson disease patients and found a significant reduction of sural sensory nerve action potential (SNAP) amplitude in eight PARK2 patients who mostly remained asymptomatic. These data suggest that sensory axonal neuropathy may be a common clinical feature of PARK2 and a reduced amplitude of sural SNAP could be a diagnostic indicator of PARK2.
Asunto(s)
Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/diagnóstico , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/etiología , Trastornos de la Sensación/diagnóstico , Trastornos de la Sensación/etiología , Nervio Sural/fisiopatología , Potenciales de Acción/fisiología , Adulto , Electrodiagnóstico , Femenino , Ganglios Espinales/metabolismo , Ganglios Simpáticos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Parestesia/diagnóstico , Parestesia/etiología , Parestesia/fisiopatología , Trastornos Parkinsonianos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , ARN Mensajero/metabolismo , Trastornos de la Sensación/fisiopatología , Ubiquitina-Proteína Ligasas/genéticaAsunto(s)
Herpes Zóster/complicaciones , Conducción Nerviosa , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Potenciales de Acción , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Electrodiagnóstico , Electromiografía , Femenino , Glucocorticoides/uso terapéutico , Herpes Zóster/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Imagen por Resonancia Magnética , Nervio Mediano/fisiopatología , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Prednisolona/uso terapéutico , Nervio Radial/fisiopatologíaAsunto(s)
Distrofias Musculares , Cromosomas Humanos Par 5/genética , Conectina , Proteínas del Citoesqueleto , Diagnóstico Diferencial , Genes Dominantes , Humanos , Proteínas de Microfilamentos , Proteínas Musculares/genética , Distrofias Musculares/clasificación , Distrofias Musculares/genética , Mutación Missense , PronósticoAsunto(s)
Distrofias Musculares , Proteínas Nucleares/genética , Cromosomas Humanos Par 1/genética , Diagnóstico Diferencial , Genes Dominantes , Bloqueo Cardíaco/etiología , Humanos , Laminas , Músculo Esquelético/patología , Distrofias Musculares/clasificación , Distrofias Musculares/genética , Mutación , PronósticoAsunto(s)
Distrofias Musculares , Cardiomiopatía Hipertrófica/etiología , Cardiomiopatía Hipertrófica/terapia , Mapeo Cromosómico , Cromosomas Humanos Par 6/genética , Diagnóstico Diferencial , Genes Dominantes , Bloqueo Cardíaco/etiología , Bloqueo Cardíaco/terapia , Humanos , Distrofias Musculares/clasificación , Distrofias Musculares/genética , PronósticoRESUMEN
We report a 52-year-old man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) presenting dementia, alopecia and lumbar herniated disk. He had an episode of stroke and migraine-like headache lasting for 5 minutes. A lot of members had cerebral infarction in this family. Brain magnetic resonance imaging demonstrated, on T2-weighted images, numerous hyperintense lesions suggestive of small infarcts in the basal ganglia and diffuse hyperintense lesions in the cerebral white matter. The clinical symptoms, the family history and the MRI findings suggested the diagnosis of CADASIL. However, the patient also showed alopecia and lumbar herniated disk, both are characteristic features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). The DNA analysis of the Notch 3 gene identified a novel missense mutation Cys174Phe in this patient. Our case report indicated the importance of the DNA analysis for the diagnosis of CADASIL.
Asunto(s)
Alopecia/complicaciones , Demencia por Múltiples Infartos/genética , Desplazamiento del Disco Intervertebral/complicaciones , Vértebras Lumbares , Mutación Missense , Proteínas Proto-Oncogénicas/genética , Receptores de Superficie Celular , Encéfalo/patología , Demencia por Múltiples Infartos/complicaciones , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , LinajeRESUMEN
Caveolin-3 is the muscle-specific isoform of the caveolin protein family, which is a major component of caveolae, small membrane invaginations found in most cell types. Caveolins play important roles in the formation of caveola membranes, acting as scaffolding proteins to organize and concentrate lipid-modified signaling molecules, and modulate a signaling pathway. For instance, caveolin-3 interacts with neuronal nitric oxide synthase (nNOS) and inhibits its catalytic activity. Recently, specific mutations in the caveolin-3 gene, including the Pro104Leu missense mutation, have been shown to cause an autosomal dominant limb-girdle muscular dystrophy (LGMD1C), which is characterized by the deficiency of caveolin-3 in the sarcolemma. However, the molecular mechanism by which these mutations cause the deficiency of caveolin-3 and muscle cell degeneration remains elusive. Here we generated transgenic mice expressing the Pro104Leu mutant caveolin-3. They showed severe myopathy accompanied by the deficiency of caveolin-3 in the sarcolemma, indicating a dominant negative effect of mutant caveolin-3. Interestingly, we also found a great increase of nNOS activity in their skeletal muscle, which, we propose, may play a role in muscle fiber degeneration in caveolin-3 deficiency.
Asunto(s)
Caveolinas/genética , Enfermedades Musculares/genética , Óxido Nítrico Sintasa/metabolismo , Animales , Western Blotting , Caveolina 3 , Caveolinas/análisis , Femenino , Expresión Génica , Genotipo , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Músculo Esquelético/química , Músculo Esquelético/patología , Enfermedades Musculares/enzimología , Enfermedades Musculares/patología , Mutación , Óxido Nítrico Sintasa de Tipo I , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy in combination with cerebral cortical dysplasia. Previously, we identified the gene responsible for FCMD, termed fukutin, through positional cloning. In this study, we have sequenced 131892 bp of genomic DNA in the region of the fukutin gene on chromosome 9q31 and obtained its complete genomic structure. The fukutin genomic sequence spans approximately 100 kb and is organized into 10 exons (41-6067 bp) and nine introns (1841-21460 bp). Using these sequence data, we have identified three novel fukutin mutations in FCMD patients. We have also located a putative TATA box in the flanking 5' region and identified numerous alternatively spliced fukutin mRNA transcripts. Analysis of expressed sequence tag clusters within the region revealed two novel genes upstream of the fukutin gene. These data provide fundamental information to support detailed genetic and functional analyses of the fukutin gene.
Asunto(s)
ADN/genética , Genes/genética , Distrofias Musculares/genética , Proteínas/genética , Empalme Alternativo , Sustitución de Aminoácidos , Secuencia de Bases , Preescolar , ADN/química , Análisis Mutacional de ADN , Exones , Salud de la Familia , Femenino , Expresión Génica , Humanos , Lactante , Intrones , Masculino , Proteínas de la Membrana , Datos de Secuencia Molecular , Distrofias Musculares/congénito , Mutación , Mutación Puntual , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , ARN Mensajero/metabolismo , Secuencias Repetitivas de Ácidos Nucleicos , Análisis de Secuencia de ADN , TATA Box , Distribución Tisular , Transcripción GenéticaRESUMEN
Alkynethiolato and alkyneselenolato complexes of ruthenium, CpRu(PPh(3))(2)(EC(triple bond)CR) (Cp = eta(5)-C(5)H(5); E = S, R = Ph (1a), SiMe(3) (1b), (t)Bu (1c); E = Se, R = Ph (2a), SiMe(3) (2b)), were synthesized by the reactions of CpRuCl(PPh(3))(2) with corresponding lithium alkynechalcogenolates in THF. An analogous reaction of Cp*RuCl(PEt(3))(2) (Cp* = eta(5)-C(5)Me(5)) with LiSC(triple bond)CPh produced Cp*Ru(PEt(3))(2)(SC(triple bond)CPh) (3). Complexes 1a and 2a were allowed to react in THF with "Cp(2)Zr", generated in situ from Cp(2)ZrCl(2) and 2 equiv of n-BuLi, from which the S-bridged Ru-Zr dinuclear complexes CpRu(PPh(3))(C(triple bond)CPh)(mu-S)ZrCp(2) (4a) and CpRu(PPh(3))(C(triple bond)CPh)(mu-Se)ZrCp(2) (4b) were isolated, respectively. In these complexes, C-S(Se) bond cleavage of the alkynechalcogenolate ligands was promoted by "Cp(2)Zr", and the Zr atom was oxidized from II to IV. Treatment of 4a and 4b in THF under 1 atm CO gave rise to CpRu(CO)(C(triple bond)CPh)(mu-E)ZrCp(2) (E = S (5a), Se (5b)), while addition of tert-butyl isocyanide to a THF solution of 4b afforded CpRu(CN(t)()Bu)(C(triple bond)CPh)(mu-Se)ZrCp(2) (6). The crystal structures of 1a, 1c, 2a, 2b, 3, 4a, 4b, and 5b were determined by X-ray diffraction analysis.