RESUMEN
AIM: To test whether actin stabilization by jasplakinolide induces inhibition of cell viability and apoptosis in epithelial cell rests of Malassez (ERM). METHODOLOGY: ERM derived from porcine were spread in a 96-well dish (5 × 10(4) /well) using Dulbecco's modified Eagle's medium. The actin-specific stabilization reagent, jasplakinolide, was incorporated into the culture medium and incubated for 24 h. To evaluate cell viability, the WST-1 assay was carried out and absorption (450 nm) was measured. To detect apoptotic cells, monoclonal antibody to single-strand DNA (ssDNA) was used and absorption (405 nm) was measured. Actin stabilization and apoptosis induced by jasplakinolide were morphologically investigated by staining with Alexa Fluor 568 phalloidin and observed under a fluorescent microscope. As a negative control, DMSO was used instead of jasplakinolide. Differences between the jasplakinolide-treated group and the control group were analysed statistically using the Student's t-test. RESULTS: Cell viability decreased in a concentration-dependent manner, and cell viability in the jasplakinolide-treated ERM was lower than that in nontreated ERM (n = 16, P < 0.01). Apoptotic cells in the jasplakinolide-treated ERM were more frequently detected compared to that in nontreated ERM (n = 16, P < 0.01). Morphologically, shrinkage, irregular forms and fragmentation of nuclei suggesting apoptotic bodies were observed in jasplakinolide-treated ERM, whilst actin filaments were extended in non-treated ERM. CONCLUSION: Actin stabilization by jasplakinolide inhibited cell viability and induced apoptosis in epithelial cell rests of Malassez.
Asunto(s)
Actinas/fisiología , Apoptosis/fisiología , Células Epiteliales/fisiología , Ligamento Periodontal/fisiología , Actinas/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Depsipéptidos/farmacología , Células Epiteliales/efectos de los fármacos , Ligamento Periodontal/citología , Porcinos , Raíz del Diente/citología , Raíz del Diente/fisiologíaRESUMEN
AMP-activated protein kinase (AMPK) is a stress-responsive enzyme involved in cell adaptation to an energy crisis. We hypothesized that hypoxia suppresses oxidative phosphorylation and ATP production, resulting in AMPK activation to protect cells. We investigated the effects of hypoxia on cell proliferation, the expression of AMPK and hypoxia-inducible factor 1alpha (HIF-1alpha), the activation of AMPK, and the relationship between AMPK and HIF-1alpha expression in rat dental pulp RPC-C2A cells. AMPK in the cells was composed of catalytic alpha1, and regulatory beta1 and gamma1 subunit isoforms. Cell proliferation was initially suppressed under hypoxia, but it increased thereafter, together with an increase in the expression of AMPK and HIF-1alpha, and the activation of AMPK. Down-regulation of AMPKalpha1 by siRNA inhibited cell proliferation under both normoxia and hypoxia, revealing that AMPK induction and activation were required for cell proliferation, although HIF-1alpha expression under hypoxia was not affected.
Asunto(s)
Pulpa Dental/enzimología , Hipoxia/enzimología , Complejos Multienzimáticos/biosíntesis , Proteínas Serina-Treonina Quinasas/biosíntesis , Proteínas Quinasas Activadas por AMP , Análisis de Varianza , Animales , Western Blotting , Línea Celular , Proliferación Celular , Pulpa Dental/citología , Activación Enzimática , Inducción Enzimática , Hipoxia/fisiopatología , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Isoenzimas , ARN Interferente Pequeño/fisiología , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no ParamétricasRESUMEN
Thirty-six patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy were studied by electroencephalogram. Twenty-two of 36 patients showed mild to moderate electroencephalographic abnormalities, ranging from poor organization or slowing of the background activity to theta bursts and/or spikes. None of these abnormalities were considered specific for HTLV-I-associated myelopathy. These electroencephalographic abnormalities had no apparent relationship to duration or severity of illness, nor to HTLV-I antibody titers in the cerebrospinal fluid. We document electroencephalographic changes in HTLV-I-associated myelopathy. Our data are consistent with previous reports describing the fact that involvement of regions above the spinal cord may exist in HTLV-I-associated myelopathy.
Asunto(s)
Electroencefalografía , Infecciones por HTLV-I/complicaciones , Enfermedades de la Médula Espinal/etiología , Adulto , Anciano , Electrooculografía , Potenciales Evocados Visuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Enfermedades de la Médula Espinal/fisiopatología , Factores de TiempoRESUMEN
We studied lactate and pyruvate concentrations in CSF and blood of a patient with Kearns-Sayre syndrome (KSS), 3 patients with ocular myopathy and 11 normal control subjects. We found significant elevation of lactate and pyruvate in the CSF of the patient with KSS, suggesting a disorder of CNS lactate-pyruvate metabolism.
Asunto(s)
Síndrome de Kearns-Sayre/líquido cefalorraquídeo , Lactatos/líquido cefalorraquídeo , Oftalmoplejía/líquido cefalorraquídeo , Piruvatos/líquido cefalorraquídeo , Adulto , Femenino , Humanos , Síndrome de Kearns-Sayre/patología , Masculino , Persona de Mediana Edad , Mitocondrias Musculares/ultraestructuraRESUMEN
We found the association of a heterozygous novel MPZ gene point mutation, Ile62Phe in exon 2, with autosomal dominant motor and sensory neuropathy with focally folded myelin sheaths. Family study revealed that de novo Ile62Phe mutation on the MPZ gene occurred in the proband and was inherited by her children with early onset slowly progressive neuropathy. Our study suggests that the characteristic pathologic findings of the sural nerve in these patients are closely related to the site and nature of amino acid substitutions of the MPZ gene.
Asunto(s)
Neuropatía Hereditaria Motora y Sensorial/genética , Vaina de Mielina/genética , Mutación Puntual , Niño , Preescolar , Cromosomas Humanos Par 1/genética , Exones , Femenino , Humanos , Microscopía Electrónica , Linaje , Nervio Sural/ultraestructuraRESUMEN
Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) has been reported as a new type of HMSN with the disease gene locus in the 3p14.1-q13 region. To further narrow down the gene locus, we performed fine linkage mapping using the linkage disequilibrium method. Analysis of DNA marker haplotypes and genetic cross-over sites showed the disease gene locus to be in the 3.1 cM interval bracketed by D3S1591 and D3S1281. Linkage disequilibrium analysis with DISMULT using 9 marker loci jointly in this region showed a lod score of 4.93 (P < 0.00000095). Consequently, the HMSN-P gene almost certainly lies on chromosome 3q13.1 and shows evidence of linkage disequilibrium.
Asunto(s)
Cromosomas Humanos Par 3 , Neuropatía Hereditaria Motora y Sensorial/genética , Desequilibrio de Ligamiento , Mapeo Cromosómico , Intercambio Genético , Femenino , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , LinajeRESUMEN
We report on two sisters with Dejerine-Sottas syndrome (DSS) who had a heterozygous Gly 167 Arg mutation in the myelin protein zero (MPZ) gene and hereditary stomatocytosis (HSt). Genetic haplotype analysis suggested that the allele with the MPZ gene mutation originated from maternal lineage. However, the parents, who were normal clinically and electrophysiologically, had no mutation in the MPZ gene. Therefore, the MPZ gene mutation in these sisters was due to germline mosaicism of the MPZ gene in their mother. Stomatocytosis was detected in their mother and a sister who had no neurological symptoms, and therefore autosomal dominant HSt was suspected in this family. As stomatocytosis is very severe in our patients with DDS, we speculate that the association of DSS with stomatocytosis is coincidental but may have additively affected erythrocyte morphology. To our knowledge, these are the first familial cases of DSS with a mutation due to germline mosaicism of the MPZ gene to be reported.
Asunto(s)
Anemia Hemolítica Congénita/genética , Neuropatía Hereditaria Motora y Sensorial/genética , Mosaicismo/genética , Proteína P0 de la Mielina/genética , Adulto , Sustitución de Aminoácidos/genética , ADN/análisis , ADN/genética , Recuento de Eritrocitos , Membrana Eritrocítica/química , Eritrocitos/fisiología , Eritrocitos/ultraestructura , Familia , Femenino , Genes Recesivos/genética , Haplotipos , Neuropatía Hereditaria Motora y Sensorial/sangre , Neuropatía Hereditaria Motora y Sensorial/patología , Humanos , Mutación/fisiología , Linaje , Nervio Sural/patologíaRESUMEN
Nucleotide sequences of two HTLV-I proviruses isolated from Indian patients with HAM/TSP were analyzed. The sequence data of the env, pX, and LTR regions showed 98-99% homologies with the prototype HTLV-I, ATK-1, isolated from a Japanese ATL patient, indicating that HTLV-I isolates in India and Japan are similar, with minor variations. However, certain small sequences of noncoding regions in the pX and LTR showed differences of 6.1 and 7.2%, respectively, thus the conclusion could vary depending on the regions and length of the sequences used for comparison.
Asunto(s)
Genes Virales/genética , Virus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/genética , Provirus/genética , Adulto , Secuencia de Bases , Femenino , Genes env/genética , Genes pX/genética , Variación Genética , Humanos , India/epidemiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Paraparesia Espástica Tropical/epidemiología , Secuencias Repetitivas de Ácidos Nucleicos/genética , Homología de Secuencia de Ácido NucleicoRESUMEN
The main lesion site of HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the pyramidal tract. In some HAM patients, clinical symptoms and findings indicate neuromuscular involvement, such as muscular atrophy, fasciculation, elevated serum creatine kinase (CK) or significant electrophysiological data. Cases of HAM/TSP complicated with polymyositis or motor neuron disease have been reported. But no investigation has been directed to muscular pathology in many patients of HAM/TSP. We conducted muscle biopsies on 13 HAM patients. Four patients showed neurogenic changes. Six patients showed histological findings indicative of inflammatory myopathy. We investigated surface marker of invading cells in these 6 patients. In all patients, T lymphocytes were more predominant than B lymphocytes and in three of them T helper/inducer cells were more predominant than T suppressor cells. In 2 patients, only slight myopathic change could be seen, such as variation in fiber diameter and increase in the number of internal nuclei. In 1 patient, type 2 fiber atrophy was seen, and was possibly the result of disuse. Disturbance of secondary motor neurons or inflammatory myopathy is thus shown to be possibly associated with HAM/TSP.
Asunto(s)
Infecciones por HTLV-I/patología , Músculos/patología , Adulto , Anciano , Atrofia , Electromiografía , Femenino , Infecciones por HTLV-I/fisiopatología , Humanos , Macrófagos/patología , Masculino , Persona de Mediana Edad , Músculos/fisiopatología , NecrosisRESUMEN
Lysinuric protein intolerance (LPI) is a rare hereditary disorder manifesting hyperammonemia induced by low levels of basic amino acids, these low levels being due to the impaired transport of these acids in the intestinal mucosa and the renal tubules. Low serum arginine levels and probably the consequently low in vivo levels of nitric oxide (NO), which against acts as a physiological and immunological mediator/modulator, are thought to influence the immunological status in patients with LPI. Accordingly, this study was conducted to. We found that patients with LPI had leukocytopenia, high serum IgG levels, a high ratio of CD44B4-positive lymphocytes (helper inducer) to CD42H4-positive lymphocytes (suppressor inducer), low levels of leukocyte phagocytic, cytotoxic, and natural killer cell activity, and increased spontaneous proliferation of lymphocytes. These results were probably the consequence of persistent low NO levels in vivo.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/inmunología , Enfermedades del Sistema Inmune/orina , Lisina/orina , Adulto , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Arginina/sangre , Femenino , Humanos , Enfermedades del Sistema Inmune/sangre , Masculino , Óxido Nítrico/sangreRESUMEN
We present a 73 year-old Japanese woman with localized scleroderma involving the right side of the scalp accompanied by continuous tingling pain, who developed insidiously progressive left hemiparesis. In magnetic resonance imaging of the brain, an infarct first appeared in the watershed region of the right middle cerebral artery territory and subsequently extended to deep white matter accompanied by scattered hemorrhages. Focal stenosis in the M2 portion of the right middle cerebral artery was revealed on magnetic resonance angiography, and the distal vessels were only shown faintly. A biopsy specimen from the sclerotic scalp lesion showed obvious thickening of vessel walls and mild mononuclear cell infiltration. We believe that the progressing ischemic stroke was caused by hemodynamic disturbances from localized sclerotic obstruction of the middle cerebral artery, with an autoimmune pathogenesis.
Asunto(s)
Infarto Cerebral/complicaciones , Esclerodermia Localizada/complicaciones , Anciano , Arteriolas/patología , Encéfalo/patología , Arterias Cerebrales/patología , Infarto Cerebral/diagnóstico , Colágeno/análisis , Progresión de la Enfermedad , Femenino , Hemiplejía/etiología , Humanos , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Cuero Cabelludo/patología , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/patologíaRESUMEN
Miyoshi myopathy, an autosomal recessive muscular dystrophy involving distal muscles, is caused by dysferlin mutations. We present clinical and genetic studies of two men and six women, aged 25-83 years, from a Japanese family with consanguineous marriages. Onset was between ages 17 and 59 years. Six of the patients had muscle involvement typical of Miyoshi myopathy, one initially had severe proximal muscle involvement, and one had scapuloperoneal-type muscle involvement. Three patients showed steppage gait. Genetic linkage analysis identified a maximum lod score of 3.34 (θ=0.00) at marker D2S292 in 2p13. Analysis of dysferlin revealed the mutation G2090T (Glu573Stop) in exon 19 in all affected patients. This is the largest Japanese family with Miyoshi myopathy showing intrafamilial phenotypic variation and sharing a common mutation in dysferlin.
Asunto(s)
Exones/genética , Proteínas de la Membrana , Proteínas Musculares/genética , Distrofias Musculares/genética , Mutación/genética , Adulto , Anciano , Anciano de 80 o más Años , Codón sin Sentido , ADN/análisis , ADN/genética , Disferlina , Familia , Femenino , Ligamiento Genético/genética , Humanos , Japón , Masculino , Persona de Mediana Edad , Debilidad Muscular/fisiopatología , Linaje , FenotipoRESUMEN
We report a case of non-fluminent and mildly affected tetanus patient who showed afterdischarges following F waves in the affected extremity. The afterdischarges occurred following F waves and showed different configuration respond to each stimuli. Diazepam was also effective for spasms of our patient. This finding disappeared after treatment and showed a good correlation to clinical symptoms. These observations suggest that afterdischarges following F waves are induced by tetanus toxin which puts most of the motor neuron pool in a hyperactive state through its own action to the motor nerve including the spinal motor neuron.
Asunto(s)
Potenciales de Acción/fisiología , Nervios Periféricos/fisiopatología , Tétanos/fisiopatología , Anciano , Electromiografía , Femenino , HumanosRESUMEN
We report a 20-year-old man with intractable myasthenia gravis successfully treated with total lymphoid irradiation (TLI). An encapsulated thymoma in the anterior mediastinum was resected as extended thymectomy by video-assisted thoracoscopic surgery at 2 months after the onset of ptosis and muscle weakness. Following treatments, such as ambenonium hydrochloride, an immunosuppression therapy (prednisolone and azatioprine), 5 courses of immunoadsorption therapy, and a high dose of cyclophosphamide and methylprednisolone, did not make persistent improvement of myasthenic symptoms. Ageusia occurred twice prior to myasthenic crises and subsided with other myasthenic symptoms after treatments. Steroid psychosis and secondary Cushing's syndrome made us to reduce the dose of prednisolone. Post-operative residual, recurrent, or metastatic thymus was not unveiled, then we added the low dose fractionated irradiation (1.5 Gy x 12 = 18 Gy) to the mediastinum. Three months after the irradiation, however, a crisis occurred and the titer of anti-acetylcholine receptor antibody increased up to 100 nmol/l. Therefore, we performed TLI (Mantle; 1.5 Gy x 9 = 13.5 Gy, paraaortic and inverted-Y; 1.5 Gy x 14 = 21 Gy), which brought about persistent improvement of myasthenic symptoms with decrease in the titer of anti-acetylcholine receptor antibody.
Asunto(s)
Irradiación Linfática , Miastenia Gravis/radioterapia , Adulto , Terapia Combinada , Humanos , Masculino , Miastenia Gravis/tratamiento farmacológico , Autotolerancia , Timoma/complicaciones , Neoplasias del Timo/complicaciones , Resultado del TratamientoRESUMEN
Rigid spine syndrome (RSS) is clinically characterized by progressive limitation of flexion of the spine and contractures of other joints. We herein report a 27-year-old man with RSS, who underwent tracheotomy because of severe restrictive respiratory failure. He had limitation of neck flexion and proximal muscle weakness from early childhood and was diagnosed as having muscular dystrophy at 16 years old. He was suffered from dyspnea and his first tracheotomy was performed at 24 years old. Two years later, the second tracheotomy was done because his respiratory failure was aggravated. He had limitation of spine flexion, scoliosis, but no limited range of elbow and wrist joints movement except mild contracture of ankle joints. Serum CK level was elevated to 590 IU/L. Repeated ECG examinations showed negative T wave but no conduction block. In his family, his parents and brother had neither similar clinical symptoms nor heart block. Chest X-ray study showed elevated diaphragm and enlarged heart shadow (CTR = 65%). Percent VC and FEV1 in sitting position were 14.6% and 100%, respectively. Arterial blood gas analysis showed PaO2 of 34.2 mmHg and PaCO2 of 77.2 mmHg. The density of paraspinal muscle in CT scan was severely decreased. Needle EMG showed myogenic change. Muscle biopsy from left biceps brachii showed myopathic change with mild type 2 fiber grouping. After the second tracheotomy, he was on a respiratory during sleep but mostly off in the daytime. His clinical features are different from Emery-Dreifuss muscular dystrophy because he had no heart conduction block and no family history, but progressive respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Insuficiencia Respiratoria/etiología , Enfermedades de la Columna Vertebral/complicaciones , Adulto , Contractura/complicaciones , Humanos , Artropatías/complicaciones , Masculino , Distrofias Musculares/complicaciones , Insuficiencia Respiratoria/cirugía , Síndrome , TraqueotomíaRESUMEN
We report a case of a 53-year-old female HTLV-1 carrier with tabes dorsalis. In addition to typical symptoms of tabes dorsalis, she presented HTLV-1 associated myelopathy (HAM) like clinical features such as sensory disturbance with thoracic sensory levels and bladder disturbance (pollakiuria). Although penicillin treatment did not improve in her neurological symptoms, steroid therapy was effective especially in HAM like symptoms. The CSF neopterin level was markedly decreased after steroid therapy, indicating that inflammation in the spinal cord was settled down after treatment. Our case suggests that CNS infection like tabes dorsalis may be modified by HTLV-1 infection and then present some atypical clinical features based upon altered immunological aspects of HTLV-1 carriers.
Asunto(s)
Portador Sano , Infecciones Oportunistas/complicaciones , Paraparesia Espástica Tropical/complicaciones , Tabes Dorsal/complicaciones , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The patient is a 33-year-old male and his parents are first cousins. He noticed his hair loss since about the age 14. At age 29, he manifested gait disturbance and urinary incontinence, which gradually progressed. Neurologically, he showed dementia (WAIS < 64), pyramidal and extrapyramidal signs, and pseudobulbar palsy. His blood pressure was normal. He also had dry skin with sclerema and marked cervical and lumbar spondylosis. His brain CT showed enlargement of the lateral ventricles and the periventricular low density areas. T2 weighted image of MRI showed diffuse high intensity in the periventricular white matter. Yamada et al presented a case progressive subcortical vascular encephalopathy (Binswanger type) with alopecia and spondylosis as a possible new syndrome, and this patient has the same syndrome. The etiology of this syndrome has not been known at the present time. The biopsied skin from the patient showed much hyaline deposits like glycoprotein in perivascular area of dermis. These morphological changes are very similar to those of lipoid proteinosis. These findings suggested that the pathological mechanism of this syndrome might be related to the biochemical disturbance in lipoid proteinosis.
Asunto(s)
Alopecia/complicaciones , Demencia Vascular/complicaciones , Osteofitosis Vertebral/complicaciones , Adulto , Demencia/complicaciones , Humanos , Masculino , Piel/patologíaRESUMEN
A 29-year-old Japanese man with Duchenne muscular dystrophy was placed on a mechanical ventilator support at 23 years of age and admitted to our hospital at 25 years of age. He had severe neck contracture deviated to the left side which resulted in dysphagia and microaspiration. At 29 years of age, he developed left lobar pneumonia accompanied by slight fever, back pain and a foul odor from the patient's sputum. Although the patient received broad spectrum antibiotics, pneumonia disseminated to the right lung. A week later, chest computed tomography was conducted which revealed tracheopulmonary-subcutaneous fistula, and a massive subcutaneous abscess with free air production. Drainage from the subcutaneous abscess was done through a chest tube; however, respiratory hypercapnia was not corrected and the patient died. From the culture of drained fluid, anaerobic bacteria including peptostreptococcus sp. were detected. This tracheopulmonary-subcutaneous fistula was thought to be caused by chronic microaspiration of mouth anaerobes, mechanical injury of the trachea under long term ventilator support, and decreased deep back muscle bulk with substitution of adipose tissue around the chest.
Asunto(s)
Absceso/etiología , Bacterias Anaerobias , Infecciones Bacterianas/etiología , Fístula Cutánea/etiología , Enfermedades Pulmonares/etiología , Distrofia Muscular de Duchenne/complicaciones , Respiración Artificial/efectos adversos , Fístula del Sistema Respiratorio/etiología , Enfermedades de la Piel/etiología , Enfermedades de la Tráquea/etiología , Enfermedad Aguda , Adulto , Humanos , Masculino , Neumonía Bacteriana/etiología , Insuficiencia Respiratoria/etiologíaRESUMEN
Anti-HTLV-I antibody was measured in 69 cerebrospinal fluids (CSFs) of cases with typical HTLV-I associated myelopathy (HAM) and other disorders whose symptoms were similar to HAM in order to evaluate the diagnostic significance of anti-HTLV-I antibody in CSF. Both gelatin particle agglutination (PA; Serodia-ATLA) method and recombinant gag-env hybrid protein coated ELISA were employed simultaneously. Antibody titers of both methods showed linear correlation. Cases with typical HAM (24 cases) and HAM with additional neurological manifestations (7 cases) showed high positivity in both methods. Cases with other neurological disorders with possible HAM (11 cases, seropositive) and cases with other neurological disorders without HAM (12 cases, seropositive) showed low positivity with low titer in ELISA, on the other hand, 81% and 67% of those cases were positive in PA method. All cases with seronegative neuroimmunological disorders (15 cases) were negative in CSFs. These findings showed that anti-HTLV-I antibody in CSF is significant in diagnosis of HAM, and both PA and gag-env ELISA are useful to detect anti-HTLV-I antibodies in CSF.