RESUMEN
BACKGROUND: Nearly all epidemiologic studies examining the association between the risk of Parkinson's disease (PD) and diet have focused on single foods and specific nutrients. However, epidemiologic evidence for the association of dietary pattern with PD, namely the measurement of overall diet by considering the cumulative effects of nutrients is extremely limited. We conducted a hospital-based case-control study in Japan to examine the relationship between dietary patterns and the risk of PD. METHODS: Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n = 249) and controls without neurodegenerative diseases (n = 368) were recruited. At the time of recruitment, dietary intake during the preceding 1 month was assessed using a validated, self-administered diet history questionnaire. Dietary patterns from 33 predefined food groups (energy-adjusted food g/day) were extracted by factor analysis. RESULTS: Three dietary patterns were identified: 'Healthy', 'Western' and 'Light meal' patterns. After adjustment for potential non-dietary confounding factors, the Healthy pattern, characterized by a high intake of vegetables, seaweed, pulses, mushrooms, fruits and fish, was inversely associated with the risk of PD with a border-line significance (P for trend = 0.06). Multivariate Odds ratio (95% confidence intervals) for PD in the highest quartile of the Healthy pattern was 0.54 (0.32-0.92) compared with the lowest quartile. No associations with PD were detected for the other two dietary patterns. CONCLUSION: In this case-control study in Japan, a dietary pattern consisting of high intakes of vegetables, fruits and fish may be associated with a decreased risk of PD.
Asunto(s)
Dieta , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/etiología , Anciano , Estudios de Casos y Controles , Dieta/efectos adversos , Análisis Factorial , Conducta Alimentaria , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Fenómenos Fisiológicos de la Nutrición , Enfermedad de Parkinson/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: antioxidant vitamins are expected to protect cells from oxidative damage by neutralizing the effects of reactive oxygen species. However, epidemiological evidence regarding the associations between antioxidant vitamin intake and Parkinson's disease (PD) is limited and inconsistent. We investigated the relationship between dietary intake of selected antioxidant vitamins, vegetables and fruit and the risk of PD in Japan using data from a multicenter hospital-based case-control study. METHODS: included were 249 patients within 6 years of onset of PD. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, body mass index, dietary intake of cholesterol, alcohol, total dairy products, and coffee and the dietary glycemic index. RESULTS: higher consumption of vitamin E and ß-carotene was significantly associated with a reduced risk of PD after adjustment for confounders under study: the adjusted odds ratio in the highest quartile was 0.45 (95% confidence interval [CI]: 0.25-0.79, P for trend = 0.009) for vitamin E and 0.56 (95% CI: 0.33-0.97, P for trend = 0.03) for ß-carotene. Stratified by sex, such inverse associations were significant only in women. No material relationships were shown between intake of vitamin C, α-carotene, cryptoxanthin, green and yellow vegetables, other vegetables, or fruit and the risk of PD. CONCLUSIONS: higher intake of vitamin E and ß-carotene may be associated with a decreased risk of PD.
Asunto(s)
Antioxidantes/administración & dosificación , Dieta , Enfermedad de Parkinson/etiología , Riesgo , Vitamina E/administración & dosificación , beta Caroteno/administración & dosificación , Anciano , Estudios de Casos y Controles , Encuestas sobre Dietas , Femenino , Humanos , Japón , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Encuestas y Cuestionarios , VerdurasRESUMEN
BACKGROUND: Hereditary neuralgic amyotrophy (HNA), also known as hereditary brachial plexus neuropathy, has phenotypic and genetic heterogeneity. Mutations in the septin 9 (SEPT9) gene were recently identified in some HNA patients. The phenotypic spectrum of HNA caused by SEPT9 mutations is not well known. OBJECTIVE: To characterise the phenotype of a large family of HNA patients with the SEPT9 R88W mutation. METHODS: We report clinical, electrophysiological, neuroimaging and genetic findings of six HNA patients from a Japanese family. RESULTS: All 17 neuropathic episodes identified were selectively and asymmetrically distributed in the upper-limb nerves. Severe pain was an initial symptom in 16 episodes (94%). Motor weakness occurred in 15 (88%) and sensory signs in 10 (59%). A minor dysmorphism, hypotelorism, was seen in all. Nerve conduction studies revealed focal demyelination as well as prominent axonal degeneration changes. Needle electromyography revealed chronic neurogenic patterns only in the upper limbs. An MRI study showed a gadolinium-enhanced brachial plexus. The missense mutation c.262C>T; p.R88W was found in exon 2 of SEPT9 in all patients. CONCLUSIONS: The SEPT9 R88W mutation in this family causes selective involvement of the brachial plexus and upper-limb nerves. Wider and more universal recognition of clinical hallmarks and genetic counselling are of diagnostic importance for HNA caused by the SEPT9 mutation.
Asunto(s)
Neuritis del Plexo Braquial/genética , Proteínas del Citoesqueleto/genética , Proteínas de Unión al GTP/genética , Mutación Missense/genética , Adolescente , Adulto , Anciano , Brazo/inervación , Plexo Braquial/patología , Niño , Familia , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Debilidad Muscular/genética , Linaje , Fenotipo , Septinas , Adulto JovenRESUMEN
OBJECTIVE: To assess the association between active and passive smoking and the risk of Parkinson's disease (PD), a case-control study with 249 PD patients and 369 controls was carried out in Japan. METHODS: Information on smoking was obtained through a self-administered questionnaire. Adjustment was made for age, sex, region of residence, educational level, and occupational exposure. RESULTS: Ever having smoked cigarettes was associated with a reduced risk of PD [adjusted odds ratio = 0.38; 95% confidence interval (CI): 0.24-0.59]. Risk for former smokers was intermediate between the high risk for never smokers and the low risk for current smokers. Adjusted odds ratios for former and current smokers were 0.51 (95% CI: 0.32-0.82) and 0.12 (95% CI: 0.05-0.26), respectively. There was an inverse dose-response gradient with pack-years smoked. No significant association was detected for passive smoking exposure. CONCLUSION: Our results appear to confirm data from previous epidemiological studies.
Asunto(s)
Enfermedad de Parkinson/etiología , Contaminación por Humo de Tabaco/efectos adversos , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Japón/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedad de Parkinson/epidemiología , Factores de Riesgo , Encuestas y Cuestionarios , Contaminación por Humo de Tabaco/estadística & datos numéricosRESUMEN
A mutein, F4168, of human tumor necrosis factor alpha (hTNF-alpha) containing the cell-adhesive Arg-Gly-Asp (RGD) sequence near the N terminus was constructed. In contrast to hTNF-alpha, the mutein had binding activity to B16F10/L5 melanoma cells similar to that of fibronectin or laminin, indicating that the adhesive nature of the RGD sequence is conferred upon hTNF-alpha. Introduction of the RGD sequence did not alter the antitumor potential of hTNF-alpha. Simultaneous injection of F4168 and B16F10/L5 melanoma cells into mice did not enhance metastasis formation in lungs, whereas hTNF-alpha significantly promoted it. Enhancement of spontaneous lymph node metastasis of B16F10/L5 cells was also evident in TNF-alpha- but not in F4168-treated mice. In the spontaneous lymph node metastasis model of MethA fibrosarcoma, F4168 injection inhibited metastasis formation more effectively than hTNF-alpha. B16F10/L5 melanoma cells treated with hTNF-alpha enhanced not only their binding activity to laminin but also their invasive potential into Matrigel, whereas F4168 showed no such enhancement. These results suggest that F4168 is a low-toxicity mutein of hTNF-alpha.
Asunto(s)
Adhesión Celular , Metástasis de la Neoplasia , Oligopéptidos/fisiología , Proteínas Recombinantes de Fusión/fisiología , Factor de Necrosis Tumoral alfa/fisiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Muerte Celular , Fibrosarcoma/secundario , Humanos , Neoplasias Pulmonares/secundario , Metástasis Linfática , Melanoma Experimental/patología , Melanoma Experimental/secundario , Ratones , Datos de Secuencia Molecular , Mutagénesis Insercional , Oligopéptidos/genética , Proteínas Recombinantes de Fusión/genética , Neoplasias Cutáneas/secundario , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
To eliminate systemic toxicity, including the hypotension associated with human tumor necrosis factor alpha (TNF-alpha), we constructed mutant proteins (muteins) by mean of genetic engineering. A novel mutein, F4614, containing mutations of 5Thr-->Gly and 6Pro-->Asp, which resulted in the introduction of cell-adhesive Arg-Gly-Asp and 29Arg-->Val, had remarkably reduced hypotensive effects and lower lethality. We present evidence that the Arg-->Val mutation at position 29 is largely responsible for the reduced hypotensive effect. This effect of F4614 was thought to be closely correlated with its low inducibility of nitric oxide and prostaglandin E2 in vivo. In addition, the therapeutically effective dose of F4614 to MethA fibrosarcoma-transplanted mice was increased compared with that of TNF-alpha, indicating a wide therapeutic index. These results indicated that F4614 has several advantages as a systemic therapeutic drug in the treatment of cancer.
Asunto(s)
Antineoplásicos/toxicidad , Ingeniería Genética , Hipotensión/prevención & control , Factor de Necrosis Tumoral alfa/toxicidad , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Humanos , Hipotensión/inducido químicamente , Masculino , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Trasplante de Neoplasias , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/toxicidad , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
The injection of B16F10 melanoma cells with recombinant human tumor necrosis factor alpha (TNF-alpha) into the tail vein of C57BL/6 mice resulted in 2- to 25-fold more metastatic foci in the lungs than the injection of tumor cells alone. Clearly, TNF-alpha significantly enhanced experimental tumor metastasis. Furthermore, it enhanced the metastasis of Lewis lung carcinoma cells. In contrast, a mutein of TNF-alpha, designated as F4236, having the cell-adhesive sequence (Tyr-Ile-Gly-Ser-Arg) at the N-terminus of the TNF molecule did not enhance metastasis, but rather exhibited similar antitumor activity to wild-type TNF-alpha in fibrosarcoma-bearing mice.
Asunto(s)
Neoplasias Pulmonares/secundario , Melanoma Experimental/secundario , Factor de Necrosis Tumoral alfa/efectos adversos , Secuencia de Aminoácidos , Animales , Adhesión Celular/fisiología , Humanos , Neoplasias Pulmonares/inducido químicamente , Melanoma Experimental/inducido químicamente , Melanoma Experimental/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Mutación , Trasplante de Neoplasias , Péptidos/farmacología , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Diplopia, a common symptom in spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD) cases, is not always due to asymmetric ophthalmoplegia. We found a Japanese SCA3/MJD family, in which three patients clearly had an impairment of divergence eye movement. We thus quantitatively examined the vergence ranges in eight Japanese SCA3/MJD cases using the synoptophore test. An impairment of the vergence eye movements was found in all patients, and the vergence impairment pattern, but not the ophthalmoplegia pattern, was found to be compatible with the diplopia pattern. The diplopia in SCA3/MJD cases is, therefore, attributed, at least in part, to the impairment of the vergence eye movements.
Asunto(s)
Convergencia Ocular , Diplopía/etiología , Esotropía/etiología , Enfermedad de Machado-Joseph/complicaciones , Nervio Abducens/fisiopatología , Adulto , Diplopía/fisiopatología , Esotropía/fisiopatología , Femenino , Marcha , Humanos , Enfermedad de Machado-Joseph/genética , Masculino , Persona de Mediana Edad , Oftalmoplejía/etiología , Oftalmoplejía/fisiopatología , Linaje , Tegmento Mesencefálico/fisiopatología , Repeticiones de TrinucleótidosRESUMEN
A 63-years-old woman noticed unsteady gait at the age of 56 years and then developed dysarthria two years later. A general physical examination at age 56 revealed mild hypertrophy of both Achilles tendons. On neurological examination, she had scanning speech, moderate limb and truncal ataxia, and moderate hyperreflexia of all limbs. A soft tissue X-ray examination disclosed hypertrophy of both Achilles tendons with multiple punctate calcification. Brain MRI showed diffuse cerebellar atrophy. Motor evoked potentials in the right limb disclosed a prolonged central conduction time. Blood chemistry showed familial type IIa hypercholesterolemia (cholesterol 320 mg/dl, and LDL-cholesterol 245 mg/dl), yet cholestanol level was normal. A examination of CTX gene mutation at hot spots revealed no mutation. Her mother and two siblings also had hypertrophy of Achilles tendons as well as type IIa hypercholesterolemia. In addition, the one sibling showed mild ataxia of lower limbs, respectively. This report suggests a possible link between familial type IIa hypercholesterolemia and cerebellar degeneration syndrome clinically mimicking CTX.
Asunto(s)
Hiperlipoproteinemia Tipo II/diagnóstico , Xantomatosis Cerebrotendinosa , Tendón Calcáneo/patología , Ataxia Cerebelosa/etiología , Consanguinidad , Femenino , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hipertrofia , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
We report a 26-year-old woman who showed recurrent migrainous attacks and convulsions since her childhood. Neurological examination revealed no focal abnormality except mental retardation (MR). T2-and fluid-attenuated inversion-recovery (FLAIR)-weighted brain MRI revealed apparent high intensities in the deep subcotical white matter. Ultrastructual studies revealed an abnormal deposition of granular osmiophilic materials (GOM) on the surface of vascular smooth muscle cells in dermis. Her mother developed recurrent strokes without risk factor since age 41. A heterozygosis Arg133Cys mutation of Notch 3 gene has already presented in patient and her mother. This case might be an early stage in CADASIL before stroke onset and suggested that systemic vasculopathy was presented in this stage. The correlation between MR and phenotype of CADASIL were unclear.
Asunto(s)
Demencia por Múltiples Infartos/genética , Discapacidad Intelectual , Proteínas Proto-Oncogénicas/genética , Receptores de Superficie Celular , Adulto , Encéfalo/patología , Salud de la Familia , Femenino , Humanos , Imagen por Resonancia Magnética , Mutación , LinajeRESUMEN
This paper reports the case of a 54-year-old woman who had a history of neurofibromatosis (NF I) presenting progressive quadriplegia and urinary incontinence due to a cervical arteriovenous fistula (AVF). MRI revealed a huge flow void mass in the cervical subcutaneous tissue as well as within the spinal canal. These flow voids originated in the left vertebral artery. A high intensity lesion was observed in the spinal cord adjacent to the flow void. Angiography revealed that the cervical AVF was fed by the third segment of the left vertebral artery with a rich communication with the intraspinal veins. Furthermore, an aneurysmal dilatation of the proximal vertebral artery and occlusion of the right middle cerebral artery with moyamoya vessels were found. Endovascular treatment using a Goldvalve detachable balloon successfully obliterated the AVF. Postoperative MRI and angiography showed evidence of the disappearance of AVF and postoperatively, the patient's neurological signs improved gradually. Sixteen reported AVFs accompanied with NF were reviewed.
Asunto(s)
Fístula Arteriovenosa/complicaciones , Vértebras Cervicales/irrigación sanguínea , Neurofibromatosis 1/complicaciones , Cuadriplejía/etiología , Fístula Arteriovenosa/terapia , Embolización Terapéutica , Femenino , Humanos , Persona de Mediana Edad , Enfermedad de Moyamoya/etiologíaRESUMEN
A 75-year-old man presented a twelve-day history of double vision and retro-ocular pain with rapid deterioration of visual acuity. Neurological examination on admission demonstrated right oculomotor palsy and abducence palsy, visual loss in the right eye, and hypesthesia and pain in the right supraorbital nerve. CT scan and MRI disclosed a mass in the right orbital apex. An emergency operation via a frontotemporal extradural approach was performed to decompress the optic nerve. The anterior clinoid process and minor wing of the sphenoid were drilled to expose the optic canal and superior orbital fissure. When the periorbita just beside the optic sheath was opened, a grayish colored mass was observed beneath the superior rectus muscle. The mass was dissected from the surrounding intraorbital tissue and was removed completely. The postoperative course was uneventful. The patient experienced complete disappearance of the ocular pain and complete restoration of his visual acuity. Orbital neurinoma is a benign tumor accounting for between 2.1 and 6.8% of all orbital tumors in the large series. The salient clinical symptom is exophthalmos followed by mass palpability. However, an orbital neurinoma presenting orbital apex syndrome is quite rare. In the case with orbital apex syndrome, it is sometimes impossible to recover visual acuity even though the optic nerve decompression is promptly performed. In such a case, only an emergency approach to the lesion can rescue the visual acuity.
Asunto(s)
Nervio Abducens , Neurilemoma/complicaciones , Oftalmoplejía/etiología , Órbita/patología , Neoplasias Orbitales/complicaciones , Anciano , Enfermedades de los Nervios Craneales/etiología , Dolor Facial/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Órbita/diagnóstico por imagen , Síndrome , Tomografía Computarizada por Rayos X , Agudeza VisualRESUMEN
We herein report two patients with neurosarcoidosis presenting girdle sensation in the trunk and polyradiculoneuritis. The first patient, a 53-year-old woman, manifested subacute progressive paresthesia in all four limbs and below the Th 3 level with girdle sensation from the thorax to lower abdomen and mild weakness in the left upper limb and the bilateral lower limbs. The patient was diagnosed to have sarcoidosis based on a biopsy of the scalenus anticus lymph nodes. The second patient, a 63-year-old woman, showed an acute onset of weakness and paresthesia in all four limbs and girdle sensation from the Th 5 to Th 8 level. On examination, she demonstrated diminished tendon reflexes in all four limbs, mild to severe weakness in all four limbs, paresthesia in all four limbs and below the Th 5 level. Although Guillain-Barré syndrome was initially suspected in this patient, the presence of girdle sensation led us to examine the possibility of neurosarcoidosis. Her examination demonstrated an abnormal accumulation of gallium in the bilateral hilar lymph nodes and mediastinum on scintigraphy, an elevated CD 4/CD 8 ratio in the bronchoalveolar lavage fluid, a negative tuberculin reaction, and elevated serum lysozyme level. These findings thus fulfilled the clinical criteria for sarcoidosis. None of the two patients showed any abnormalities in the thoracic cord MRI. In the first patient F wave was not evoked in either upper or lower limbs, while in the second patient temporal dispersion on M wave was observed in the right median and both ulnar nerves. We therefore consider the girdle sensation to have not been caused by myelopathy but instead by polyradiculopathy. When sarcoid peripheral neuropathy masquerades as Guillain-Barré syndrome, then the presence of girdle sensation may help diagnosis of neurosarcoidosis.
Asunto(s)
Síndrome de Guillain-Barré/diagnóstico , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Polirradiculoneuropatía/complicaciones , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Trastornos de la Sensación/etiología , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Sarcoidosis/fisiopatologíaRESUMEN
OBJECTIVES: The efficiency of high-dose vitamin C therapy for inclusion body myositis (IBM) was assessed. SUBJECTS & METHODS: The subjects were five patients with IBM confirmed pathologically. After the intravenous administration of 40 mg/kg vitamin C five times/week for four weeks, muscle weakness was found to improve in three cases. The average muscle score improved from 8.1 to 8.8, from 7.0 to 8.1 and from 6.2 to 6.8. Magnetic resonance imaging (MRI) demonstrated a reduction in the size of T2 high lesions and gadolinium enhancement in the thigh muscles in one case. Based on our findings, high-dose vitamin C therapy is considered to be effective in some cases of IBM.
Asunto(s)
Ácido Ascórbico/administración & dosificación , Miositis por Cuerpos de Inclusión/tratamiento farmacológico , Anciano , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana EdadAsunto(s)
Dolor Facial/terapia , Dolor Intratable/terapia , Núcleo Subtalámico/patología , Carboxiliasas/antagonistas & inhibidores , Estimulación Encefálica Profunda , Dolor Facial/etiología , Femenino , Humanos , Levodopa/farmacología , Persona de Mediana Edad , Dolor Intratable/etiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Periodo Posoperatorio , Núcleo Subtalámico/fisiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Three previous cohort studies in the USA reported that dairy product consumption was significantly associated with an increased risk of Parkinson's disease (PD) in men, but not in women. We examined the relationship between consumption of dairy products, calcium, and vitamin D and the risk of PD using data from a multicenter hospital-based case-control study in Japan. Included were 249 cases within 6 years of onset of PD based on the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, body mass index, and dietary factors including cholesterol, dietary glycemic index, vitamin E, ß-carotene, vitamin B(6), caffeine, iron, and alcohol. Total dairy product consumption was not materially associated with the risk of PD (P for trend = 0.62). No evident relationships were observed between intake of milk, yogurt, cheese, or ice cream and the risk of PD (P for trend = 0.75, 0.63, 0.59, and 0.35, respectively). There were no measurable associations between consumption of calcium or vitamin D and PD (P for trend = 0.37 and 0.69, respectively). No significant interactions were observed between the dietary exposures and sex regarding PD. Our results suggest that intake of dairy products, calcium, and vitamin D was not related to PD, regardless of sex. However, such null relationships might be a consequence of PD.
Asunto(s)
Calcio de la Dieta/administración & dosificación , Calcio/administración & dosificación , Productos Lácteos , Enfermedad de Parkinson/etnología , Enfermedad de Parkinson/etiología , Vitamina D/administración & dosificación , Anciano , Calcio/efectos adversos , Calcio de la Dieta/efectos adversos , Estudios de Casos y Controles , Productos Lácteos/efectos adversos , Femenino , Humanos , Japón/etnología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Vitamina D/efectos adversosRESUMEN
Patients with idiopathic Parkinson's disease (PD) appear to have reduced capacity for detoxification of certain environmental compounds. The glutathione S-transferases (GSTs) are candidate genes for PD because they are involved in the metabolism of pesticides and cigarette smoke. We investigated the relationship of the seven GST polymorphisms (GSTM1 deletion, GSTT1 deletion, GSTP1 rs1695, GSTO1 rs4925, GSTO1 rs11191972, GSTO2 rs156697 and GSTO2 rs2297235) and PD risk with special reference to the interaction with pesticide use or cigarette smoking among 238 patients with PD cases and 370 controls in a Japanese population. None of the GST polymorphisms were associated with PD. GSTO1 rs4925 and GSTO2 rs2297235 were found to be in strong linkage disequilibrium (D' = 0.98). Cigarette smoking was significantly associated with decreased risk of PD. However, no interaction of smoking with any of the GST polymorphisms was observed. Self-reported pesticide use was not associated with increased risk of PD. There was no evidence of interaction between self-reported pesticide use and either GST polymorphism. Our results suggest that the tested GST polymorphisms did not play an important role in PD susceptibility in our Japanese population. Our study does not give evidence of interaction between the GST polymorphisms and smoking may although this study provided sufficient statistical power to detect modest interaction. As for interaction between GSTP polymorphisms and pesticide use, the power of this study to detect an interactive effect was low due to a small number of pesticide users. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the GST polymorphisms in PD development.
Asunto(s)
Glutatión Transferasa/genética , Enfermedad de Parkinson , Plaguicidas/efectos adversos , Polimorfismo Genético/genética , Fumar , Anciano , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/psicología , Grupos de Población , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The effects of human tumour necrosis factor-alpha (TNFalpha), or its mutein (F4168) having the cell adhesive Arg-Gly-Asp sequence at the N-terminus, on intestinal injury, were examined. Histopathological examination revealed that an intravenous injection of TNFalpha resulted in marked haemorrhage or oedema in the caecum of rats, whereas F4168 showed no such effects even at the same therapeutic dose. Moreover, the number of neutrophils that adhered to endothelial cells or infiltrated the mucosal tissue was much higher after TNFalpha injection compared with F4168 in vivo. The enhanced adhesion of neutrophils on to human umbilical vein endothelial cells also occurred when the latter were pre-stimulated with TNFalpha but not with F4168 in vitro. The expression of the cell adhesion molecules including endothelial leukocyte adhesion molecule-1 or intercellular adhesion molecule-1 on F4168- stimulated human umbilical vein endothelial ceils was significantly lower than that stimulated with TNFalpha. These results suggest that the Arg-Gly-Asp sequence introduced into the TNFalpha molecule abrogates the side effect of this cytokine such as tissue injury or shock, and that F4168 could be useful for systemic therapy.
RESUMEN
We report a novel type of hereditary sensory and autonomic neuropathy (HSAN) with adult onset in a Japanese family. One male and 2 females of 6 siblings were affected. They developed anosmia initially at the ages of 20-50 years, followed by anhidrosis and sensory loss. Skin ulceration was absent. Both superficial and deep sensation were impaired in the most distal parts of all 4 limbs. Orthostatic hypotension was present in all patients. This is a unique subtype of HSAN distinct from the HSAN I-V described by Dyck.