RESUMEN
Toxoplasma is a common parasite worldwide that mainly affects the brain, lungs and eyes. Although toxoplasmic encephalitis is a lethal disease without treatment, past case reports show most patients with systemic lupus erythematosus who developed toxoplasmic encephalitis were misdiagnosed and treated as neuropsychiatric systemic lupus erythematosus, which led to unfavorable outcomes. We herein describe a case of disseminated toxoplasmosis affecting all the above organs with atypical symptoms, which developed with exacerbation of systemic lupus erythematosus. She had initially manifested with retinochoroiditis without vitritis, mild cognitive impairment and an isolated lung mass. These are completely different from the classic symptoms of toxoplasmosis that have been reported in patients with HIV infection and/or those after hematopoietic transplantation. Our case, together with previously reported cases, suggests the manifestation of toxoplasmosis that develops in systemic lupus erythematosus patients can be different from that seen in conventional cases and varies between individual patients. Our case highlights both the difficulty in and the importance of diagnosing toxoplasmosis in patients with systemic lupus erythematosus and provides helpful information to identify this rare, devastating, yet treatable disease.
Asunto(s)
Lupus Eritematoso Sistémico/complicaciones , Infecciones Oportunistas/complicaciones , Toxoplasmosis Cerebral/complicaciones , Toxoplasmosis Cerebral/diagnóstico , Adulto , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Pulmón/diagnóstico por imagen , Vasculitis por Lupus del Sistema Nervioso Central/complicaciones , Imagen por Resonancia Magnética , Oftalmoscopios , Tomografía Computarizada por Rayos XRESUMEN
A quasi-spherical virus was isolated from a cultivated Amazon lily plant (Eucharis grandiflora) that could be mechanically transmitted to healthy E. grandiflora plants, subsequently producing mild mosaic or mottle symptoms on the leaves. The purified virus consisted of three quasi-spherical particles about 20 nm wide and 70, 40 and 30 nm in length, containing three segmented genomes of 3,169, 2,507 and 2,530 nucleotides, respectively. Sequence analysis showed that the newly isolated virus is related to pelargonium zonate spot virus, a member of the genus Anulavirus. We propose that the virus should be designated as Amazon lily mild mottle virus (ALiMMV).
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Bromoviridae/genética , Bromoviridae/aislamiento & purificación , Lilium/virología , Enfermedades de las Plantas/virología , Bromoviridae/clasificación , Genoma Viral , Datos de Secuencia Molecular , Filogenia , Hojas de la Planta/virologíaRESUMEN
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10(-8); odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.
Asunto(s)
Alopurinol/efectos adversos , Síndrome de Stevens-Johnson/genética , Anciano , Anciano de 80 o más Años , Alopurinol/uso terapéutico , Pueblo Asiatico/genética , Biomarcadores/metabolismo , Cromosomas Humanos Par 6/efectos de los fármacos , Cromosomas Humanos Par 6/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Estudio de Asociación del Genoma Completo/métodos , Antígenos HLA/genética , Antígenos HLA/metabolismo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Síndrome de Stevens-Johnson/inducido químicamente , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/metabolismoRESUMEN
BACKGROUND: Post-ischaemic benzodiazepine administration is neuroprotective, but chronic administration of benzodiazepines can induce tolerance, such that the neuroprotective effect may be reduced. This study investigated whether benzodiazepine tolerance can worsen ischaemic injury and whether neuroprotection by post-ischaemic benzodiazepine administration is affected by benzodiazepine tolerance. We also investigated whether antagonism of benzodiazepine receptors by flumazenil was able to restore neuroprotection during benzodiazepine tolerance. METHODS: Experiments were performed in both benzodiazepine-tolerant and naive rats. Benzodiazepine tolerance was indeed by 4 weeks administration of flurazepam. Bilateral carotid artery occlusion (BCAO) was performed to cause cerebral ischaemia. Four experiments were performed: (1) BCAO with no further interventions; (2) BCAO followed by administration of diazepam; (3) administration of flumazenil before BAO; and (4) administration of flumazenil before and diazepam after BCAO. Neurological and histological assessment was performed 5 days after BCAO. RESULTS: Benzodiazepine tolerance did not affect neuronal injury in the CA1 and CA3 regions and dentate gyrus of the hippocampus after severe ischaemic insult, but did worsen neuronal damage when mild ischaemia was applied (P<0.05). Neuroprotective efficacy of post-ischaemic diazepam was not observed under conditions of benzodiazepine tolerance. Flumazenil treatment before BCAO reduced ischaemic neuronal damage exacerbated by benzodiazepine tolerance (P<0.05), and restored neuroprotection by post-ischaemic diazepam (P<0.05), the effect of which was reduced by benzodiazepine tolerance (P<0.05). However, pre-ischaemic flumazenil treatment in naive animals reduced neuroprotection provided by post-ischaemic diazepam (P<0.01-0.05). CONCLUSIONS: Benzodiazepine tolerance can worsen ischaemic neuronal injury and abolish the neuroprotection provided by post-ischaemic diazepam. Pre-treatment with flumazenil treatment reversed benzodiazepine tolerance and restored neuroprotection by post-ischaemic diazepam. These findings may suggest that management of patient's risk of developing cerebral ischaemia may need to take into account current use.
Asunto(s)
Benzodiazepinas/farmacología , Isquemia Encefálica/patología , Diazepam/farmacología , Tolerancia a Medicamentos , Flumazenil/farmacología , Prosencéfalo/efectos de los fármacos , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Moduladores del GABA/farmacología , Masculino , Fármacos Neuroprotectores/farmacología , Prosencéfalo/irrigación sanguínea , Prosencéfalo/patología , Ratas , Ratas Sprague-Dawley , Receptores de GABA-A/efectos de los fármacos , Índice de Severidad de la EnfermedadRESUMEN
A polymerase chain reaction (PCR)-based molecular method to detect Phomopsis sclerotioides in soil was developed using a species-specific primer pair. To improve sensitivity of the detection, three PCR techniques were used; namely, nested PCR using the primer pair internal transcribed spacer (ITS)1 and ITS4, time-release PCR using two different DNA polymerases (recombinant Taq and AmpliTaq Gold), and fluorescent PCR to obtain fluorescent-labeled PCR products that can be analyzed by capillary electrophoresis. The latter two techniques were combined and termed nested time-release fluorescent (NTRF)-PCR. The minimum concentration of DNA required to obtain species-specific PCR products successfully was 50 fg/µg. Using the NTRF-PCR method, the fungus could be detected in sandy soil that was artificially infested at a density of 10 CFU/g. The pathogen was detected in most soil samples collected from commercial cucumber fields in which visual disease symptoms had appeared, and even in samples collected from fields where visual disease symptoms had not appeared. To prevent the invasion and establishment of root-inhabiting pathogens such as P. sclerotioides, it is critical to detect the fungus in soil as soon as possible after its introduction into a cucumber-growing region.
RESUMEN
Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant congenital disorder characterized by progressive heterotopic bone formation. Currently, no definitive treatment exists for FOP. The activin receptor type IA / activin-like kinase 2 (ACVR1/ALK2) gene has been identified as the responsible gene for FOP, and disease-associated ALK2 mutations have been found. Chemical inhibitors to the pathogenic ALK2 receptors are considered possible medical agents for FOP, but their adverse effects on normal ALK2 and other receptors cannot be excluded. Here we describe another treatment strategy for FOP using allele-specific RNA interference (ASP-RNAi), and show modified small interfering RNAs (siRNAs) conferring allele-specific silencing against disease-causing ALK2 mutants found in FOP, without affecting normal ALK2 allele. Thus, the siRNAs presented here may become novel therapeutic agents for FOP, and their induced ASP-RNAi may pave the way for the achievement of radical treatment of FOP and/or for the relief of its severe symptoms.
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Receptores de Activinas Tipo I/genética , Silenciador del Gen , Miositis Osificante/genética , ARN Interferente Pequeño/farmacología , Alelos , Línea Celular Tumoral , Humanos , MutaciónAsunto(s)
Anestesia Raquidea/instrumentación , Anestesia Raquidea/métodos , Punción Espinal/instrumentación , Punción Espinal/métodos , Columna Vertebral/anatomía & histología , Anestésicos/administración & dosificación , Humanos , Inyecciones Espinales , Modelos Anatómicos , Agujas , Obesidad/patología , Piel/anatomía & histología , Espacio Subaracnoideo/anatomía & histologíaRESUMEN
We report the graft replacement for surgical repair of coarctation of the aorta (CoA) in 2 men, aged 19 and 30 years old, respectively. In both patients, the pressure gradients were higher than 20 mmHg across the coarctaion by cathetherization, and higher than 30 mmHg between the upper and lower limbs. The graft replacement of the coarctated aorta was performed under cardiopulmonary bypass. Postoperatively, the pressure gradients between the upper and lower limbs dropped below 20 mmHg in both cases. Since about 50% of surgically untreated patients with this disease may be expected to die before 30 years of age, repair of CoA in adults should be performed as soon as possible.
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Coartación Aórtica/cirugía , Prótesis Vascular , Adulto , Puente Cardiopulmonar , Humanos , MasculinoRESUMEN
BACKGROUND: Beta-1-receptor blockade reduces heart rate, cardiac output, and arterial pressure while increasing peripheral vascular resistance. It is possible that beta blockers not only inhibit the core-to-peripheral re-distribution of body heat and cutaneous heat loss due to vasodilation after anesthesia induction but also reduce the convective transfer of heat from the core to peripheral tissues by decreasing cardiac output. The authors investigated whether the co-administration of esmolol or landiolol, ultra-short-acting beta blockers, attenuates the magnitude of initial re-distribution hypothermia after anesthesia induction and tracheal intubation. METHODS: Immediately prior to the induction of anesthesia, patients were randomly assigned to receive 0.2 mg kg-1 of landiolol (landiolol group; N=30), 1 mg kg-1 of esmolol (esmolol group; N=30), or 0.1 mL kg-1 of saline (control group; N=30). Heart rate, blood pressure, cardiac output, and tympanic, forearm, and digit temperatures were recorded. Forearm minus fingertip skin-surface temperature gradients (temperature gradient) were calculated. RESULTS: Tympanic membrane temperatures 15 to 60 min after the induction of anesthesia were significantly higher in the esmolol group than in the control group although the temperature gradient was similar among the three groups. Both esmolol and landiolol inhibited the increase in HR and MAP after the induction of anesthesia and tracheal intubation. The cardiac index in the esmolol group was significantly lower than in the control group. The degree of hemodynamic attenuation after induction by esmolol was larger than that of landiolol. CONCLUSION: The co-administration of esmolol, but not landiolol, attenuated the magnitude of initial re-distribution hypothermia after anesthesia induction and tracheal intubation. Esmolol likely prevented initial hypothermia because it attenuated the convective transfer of heat from the core to peripheral tissues by decreasing cardiac output.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Anestesia por Inhalación/efectos adversos , Hipotermia/inducido químicamente , Hipotermia/prevención & control , Antagonistas Adrenérgicos beta/administración & dosificación , Adulto , Anciano , Temperatura Corporal/efectos de los fármacos , Colorantes , Femenino , Procedimientos Quirúrgicos Ginecológicos , Hemodinámica/efectos de los fármacos , Humanos , Verde de Indocianina , Intubación Intratraqueal , Persona de Mediana Edad , Morfolinas/administración & dosificación , Morfolinas/uso terapéutico , Propanolaminas/administración & dosificación , Propanolaminas/uso terapéutico , Urea/administración & dosificación , Urea/análogos & derivados , Urea/uso terapéuticoRESUMEN
BACKGROUND: Xenon has been shown to reduce cellular injury after cerebral ischemia. However, the neuroprotective effects of xenon on ischemic spinal cord are unknown. The authors compared the effects of xenon and propofol on spinal cord injury following spinal cord ischemia in rabbits. METHODS: Thirty-two male New Zealand white rabbits were randomly assigned to one of three groups. In the xenon and propofol group, 70% of xenon and 0.8 mg/kg/min of propofol were administered 30 min before an aortic occlusion and maintained until the end of the procedure. The aortic occlusion was performed for 15 min. In the sham group, the aorta was not occluded. After an assessment of the hind limb motor function using the Tarlov score (0=paraplegia, 4=normal) at 48 h after reperfusion, gray and white matter injuries were evaluated based on the number of normal neurons in the anterior spinal cord and the percentage areas of vacuolation in the white matter, respectively. RESULTS: In the xenon and propofol groups, the Tarlov score and the number of normal neurons were significantly lower than those in the sham group, whereas the percentage areas of vacuolation were similar among the three groups. There were no significant differences in Tarlov scores and the number of normal neurons between the xenon and the propofol groups. CONCLUSION: The results indicated that 70% of xenon has no additional neuroprotective effects on ischemic spinal cord injury in rabbits compared with propofol.
Asunto(s)
Anestésicos por Inhalación/uso terapéutico , Anestésicos Intravenosos/uso terapéutico , Fármacos Neuroprotectores , Propofol/uso terapéutico , Isquemia de la Médula Espinal/tratamiento farmacológico , Xenón/uso terapéutico , Animales , Aorta Torácica/fisiología , Hemodinámica/fisiología , Miembro Posterior/fisiología , Masculino , Actividad Motora/fisiología , Movimiento/fisiología , Conejos , Recuperación de la Función , Médula Espinal/patología , Isquemia de la Médula Espinal/patologíaRESUMEN
Landiolol is a recently developed, selective short-acting beta1-antagonist. The aim of the study was to evaluate the efficacy of landiolol for suppressing haemodynamic changes induced by laryngoscopy and tracheal intubation (LTI) in Japanese patients. A comprehensive search was undertaken to identify all randomised comparisons of landiolol with placebo that examined effects on haemodynamic responses following LTI. MEDLINE, Cochrane CENTRAL, EMBASE and the Japanese Central Review of Medicine were searched from their date of inception to February 2009. Trials were included in the review if heart rate, systolic blood pressure or mean blood pressure was recorded at three different stages: pre-induction, just before intubation and in the post-intubation period. Weighted mean differences and 95% confidence intervals (CI) were calculated for changes in haemodynamic variables between treatment and placebo groups. Seven randomised controlled trials involving 325 patients were included in the study. Of these, five trials that used the same continuous infusion regimen for landiolol (0.125 mg/kg/minute for one minute followed by 0.04 mg/kg/minute) showed efficacy in attenuation of heart rate and blood pressure following LTI (heart rate weighted mean difference: -21.18 bpm, 95% CI -18.59 to -14.20; systolic blood pressure weighted mean difference: -23.03 mmHg, 95% CI -43.59 to -2.47; mean blood pressure weighted mean difference: -16.26 mmHg, 95% CI -23.96 to -8.55). The other two studies used bolus administration of landiolol (0.1 to 0.3 mg/kg), but it was difficult to evaluate the efficacy because of the limited amount of data. Landiolol administration at 0.125 mg/kg/minute for one minute followed by 0.04 mg/kg/minute effectively suppresses the increases in heart rate and blood pressure following LTI. For a bolus regimen of landiolol, further studies are required to determine the efficacy and the optimal dose and timing for suppression of haemodynamic responses following LTI.
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Antagonistas Adrenérgicos beta/farmacología , Laringoscopía/métodos , Morfolinas/farmacología , Urea/análogos & derivados , Antagonistas Adrenérgicos beta/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Humanos , Intubación Intratraqueal/métodos , Japón , Morfolinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Urea/administración & dosificación , Urea/farmacologíaRESUMEN
BACKGROUND: Isoflurane has been shown to induce tolerance against ischaemic injury in adult rodents. Although the delayed preconditioning effect of isoflurane has been demonstrated in neonatal rat pups, the acute preconditioning effects of isoflurane remained undetermined. The present study was therefore conducted to evaluate the acute preconditioning efficacy of isoflurane in neonatal rats subjected to a hypoxic-ischaemic (HI) injury. METHODS: Post-natal day 7 pups were exposed to 1 or 2% isoflurane in oxygen for either 30, 60 or 90 min. Fifteen minutes after isoflurane exposure, the pups were subjected to an HI injury induced by left common carotid artery ligation and exposure to 8% oxygen for 2 h. Pups not exposed to isoflurane or not subjected to HI served as controls. Histopathologic injury to the cortex and hippocampus was evaluated 7 and 49 days after HI. RESULTS: Isoflurane 2% exposure for 60 or 90 min before HI induced tolerance in the hippocampus and the number of normal neurons in the CA1 sector 7 days after HI was significantly greater than in non-preconditioned animals. This protective efficacy of isoflurane preconditioning was not observed 49 days after HI. CONCLUSIONS: Exposure of 2% isoflurane for at least 60 min is required to induce tolerance against HI injury in rat pups. However, this neuroprotective efficacy results in only transient neuroprotection.
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Hipoxia-Isquemia Encefálica/patología , Precondicionamiento Isquémico/métodos , Isoflurano/farmacología , Neuronas/efectos de los fármacos , Animales , Animales Recién Nacidos , Arterias/efectos de los fármacos , Análisis de los Gases de la Sangre , Condicionamiento Físico Animal , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
BACKGROUND: Opioids are commonly administered to critically ill neonates and infants for general anaesthesia and sedation. However, the clinical safety of these drugs, especially the effects on hypoxic-ischaemic damage of the developing brain, has not been well investigated. The present study was therefore conducted to investigate the effects of continuous morphine infusion on brain damage after hypoxic-ischaemic insults in neonatal rats. METHODS: Seven-day-old Sprague-Dawley rats were subjected to left common carotid artery ligation followed by a 90-min exposure of 8% oxygen. The rats were administered morphine (0.1, 0.3 or 1 mg/kg/h) or saline continuously for 72 h using osmotic minipumps. Seven days later, the rats were weighed and their brains were morphologically categorized into groups based on the following grades: 0=normal, 1=mild atrophy, 2=moderate atrophy, 3=atrophy with cystic cavitation <3 mm and 4=cystic cavitation >3 mm. For histological assessment, the ratio of the surviving neurons (ipsilateral/contralateral) was calculated in the cornu ammonis fields, CA1 and CA3, and the dentate gyrus (DG). RESULTS: One week after recovery (P14), the rats in the 1 mg/kg/h group showed significantly poorer weight gain compared with the other groups. However, the morphological score of the brains and the ratio of the surviving neurons in the CA1, CA3 and DG were similar among the groups. CONCLUSION: Our results indicate that continuous administration of morphine does not worsen brain damage 7 days after hypoxic-ischaemic insults in neonatal rats.
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Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Morfina/administración & dosificación , Morfina/uso terapéutico , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Infusiones Parenterales , Ratas , Ratas Sprague-DawleyRESUMEN
We have previously mapped autosomal dominant spinocerebellar ataxia (SCA) 16 to 3p26, overlapping with the locus of SCA15. Recently, partial deletions of ITPR1 and the neighbouring SUMF1 in the SCA15 and two additional families were reported. In the present study we determined the copy number of these genes by real time quantitative polymerase chain reaction (PCR) and found a heterozygous deletion of exons 1-48 of ITPR1, but not SUMF1 in SCA16. Breakpoint analysis revealed that the size of the deletion is 313,318 bp and the telomeric breakpoint is located in the middle of their intergenic region. Our data provide evidence that haploinsufficiency of ITPR1 alone causes SCA16 and SCA15.
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Heterocigoto , Receptores de Inositol 1,4,5-Trifosfato/genética , Eliminación de Secuencia , Ataxias Espinocerebelosas/genética , Secuencia de Bases , Exones/genética , Dosificación de Gen , Humanos , Datos de Secuencia Molecular , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro , Linaje , Reacción en Cadena de la Polimerasa , Sulfatasas/genéticaRESUMEN
BACKGROUND: It has been reported that delta-opioid (DOP) receptor agonists may be neuroprotective in the central nervous system. However, the DOP agonist [d-Ala(2), d-Leu(5)]enkephalin (DADLE) does not produce neuroprotection in severe forebrain ischaemia. The aim of this study was to examine the effects of DADLE on hippocampal neurone survival against less severe forebrain ischaemia. METHODS: Intraperitoneal injection of DADLE (0 or 16 mg kg(-1)) in male Sprague-Dawley rats was performed 30 min before ischaemia. Severe (10 min), moderate (8 min), or mild (6 min) forebrain ischaemia was produced by bilateral carotid occlusion combined with hypotension (35 mm Hg) under isoflurane (1.5%) anaesthesia. Naltrindole (10 mg kg(-1)) (DOP antagonist) was administered 30 min before DADLE in order to confirm DOP receptor activation in the neuroprotective efficacy of DADLE. Naltrindole alone was also administered 30 min before ischaemia to examine endogenous DOP agonism as a self-protecting mechanism against ischaemia. All animals were evaluated neurologically and histologically after a 1 week recovery period. RESULTS: DADLE improved neurone survival in hippocampal CA3 and dentate gyrus (DG) sectors. CA1 neurones were not protected against moderate and mild ischaemia. Naltrindole abolished DADLE neuroprotection in the CA3 and DG after both moderate and mild ischaemia. Interestingly, regardless of co-administration of DADLE, naltrindole significantly worsened neuronal injury in the CA1 region after mild ischaemia. CONCLUSIONS: These results suggest that DADLE provides limited neuroprotection to relatively ischaemia-resistant regions but not to selectively vulnerable regions. This was probably mediated by DOP stimulation. Pre-ischaemic treatment with a DOP antagonist, regardless of co-administration of DADLE, worsened neuronal damage at the selectively vulnerable regions only after mild forebrain ischaemia. These data suggest that DOP activation with endogenous DOP ligand may be involved in self-protecting ischaemia-sensitive regions of the brain.
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Isquemia Encefálica/prevención & control , Leucina Encefalina-2-Alanina/uso terapéutico , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Receptores Opioides delta/fisiología , Animales , Isquemia Encefálica/patología , Supervivencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Leucina Encefalina-2-Alanina/farmacología , Hipocampo/patología , Masculino , Naltrexona/análogos & derivados , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Prosencéfalo/irrigación sanguínea , Ratas , Ratas Sprague-Dawley , Receptores Opioides delta/agonistas , Receptores Opioides delta/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To identify of the gene responsible for the onset of spinocerebellar ataxia type 16 (SCA16). METHODS: We reanalyzed the linkage of the original Japanese pedigree using updated information, including three additional subjects. We then screened all exons located in the critical region. RESULTS: We reassigned the locus of SCA16 to 3p26.2-pter (maximum logarithm-of-odds score = 5.177) and identified only one point mutation (4,256C-->T) in the 3' untranslated region of the contactin 4 gene (CNTN4) on chromosome 3p26.2-26.3, which cosegregated with the disease. This mutation was not detected in 520 control subjects; moreover, we revised the phenotype of SCA16 from pure to complicated SCA. CONCLUSION: The contactin 4 gene (CNTN4) is associated with cerebellar degeneration in spinocerebellar ataxia type 16. Additional studies are necessary to prove 4,256C-->T to be a causative mutation.