RESUMEN
BACKGROUND: Sick leave from work due to psychiatric disorders is a major public health problem, not only in Japan but also worldwide. As males and females in Japan tend to differ in their approach to work, a gender difference in perfectionism might be expected. We investigated the background factors leading to long-term absence from work due to sickness among psychiatric outpatients in Japan. METHODS: We surveyed 73 psychiatric outpatients who were absent from work for a long time (POAWs) and 228 employees without long-term sickness absence as controls. GHQ-30, NEO-FFI, MPS, RSS and questionnaires inquiring about background factors, including relationships with others, was used, and the data were compared between males and females. RESULTS: Male POAWs had a significantly higher tendency for depression and perfectionism than the controls, but in females this difference was not significant. With regard to personal relationships of POAWs, males had worse relationships with superiors and colleagues, whereas females had worse relationships with superiors, colleagues, and family. CONCLUSIONS: The data suggested that male workers exhibiting perfectionism tend to undertake too much work and become exhausted when trying to cope with complex human relationships in the workplace. Female workers having the double burden of family commitment and perfectionism tend to be isolated in terms of personal relationships, leading to exhaustion both in and outside the workplace.
RESUMEN
BACKGROUND: A recent study showed that transforming growth factor-beta1 (TGF-beta1) induces amyloid-beta deposition in cerebral blood vessels and meninges of a transgenic mouse model of Alzheimer's disease (AD), and that TGF-beta1 mRNA levels are correlated with cerebral amyloid angiopathy (CAA) in human AD brains. A T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 gene has been reported to be associated with the serum TGF-beta1 concentration. We investigated whether the TGF-beta1 polymorphism is associated with the risk of CAA. METHODS: The association between the severity of CAA and the T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 was investigated in 167 elderly Japanese autopsy cases, including 73 patients with AD. The apolipoprotein E (APOE) genotype was also determined. RESULTS: The genotypes (TT/ TC/ CC) were associated with the severity of CAA significantly in all patients (p = 0.0026), in non-AD patients (p = 0.011), and APOE non-epsilon4 carriers (p = 0.0099), but not in AD patients or APOE epsilon4 carriers. The number of the T alleles positively correlated with the severity of CAA in all patients (p = 0.0011), non-AD patients (p = 0.0026), and APOE non-epsilon4 carriers (p = 0.0028), but not in AD patients or APOE epsilon4 carriers. The polymorphism was not significantly associated with AD. CONCLUSIONS: Our results suggest that the polymorphism in TGF-beta1 is associated with the severity of CAA, especially in non-AD patients and APOE non-epsilon4 carriers.
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Angiopatía Amiloide Cerebral/genética , Polimorfismo Genético/genética , Factor de Crecimiento Transformador beta/genética , Anciano , Anciano de 80 o más Años , Alelos , Enfermedad de Alzheimer/etnología , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Angiopatía Amiloide Cerebral/etnología , Angiopatía Amiloide Cerebral/metabolismo , Codón/genética , Exones/genética , Femenino , Genotipo , Humanos , Japón , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , ARN Mensajero/metabolismo , Índice de Severidad de la Enfermedad , Factor de Crecimiento Transformador beta1RESUMEN
OBJECTIVE: To investigate abnormal prion protein (PrP) deposition in the peripheral nervous system (PNS) in human prion diseases. METHODS: Eight patients with prion diseases were examined: three with sporadic Creutzfeldt-Jakob disease (sCJD), two with dural graft associated CJD (dCJD), one with Gerstmann-Straussler-Scheinker disease (GSS) with a PrP P102L mutation (GSS102), and two with a P105L mutation (GSS105). An atypical case of sCJD with PrP plaques in the brain presented clinically with peripheral neuropathy, and showed demyelination in 12% of the teased fibres of the sural nerve. The PNS was investigated by immunohistochemical and western blotting analyses of PrP. RESULTS: In immunohistochemical studies, granular PrP deposits were detected in some neurones of dorsal root ganglia and a few fibres of peripheral nerves and spinal posterior roots in one sCJD and two dCJD patients, but not in GSS102 or GSS105 patients. The atypical case of sCJD with peripheral neuropathy showed no obvious PrP deposition in the nerves. Western blotting analysis of the PNS from the dCJD patients revealed a small amount of protease K resistant PrP in the dorsal root ganglia and peripheral nerves. CONCLUSIONS: Abnormal PrP deposition occurs in the dorsal root ganglia and peripheral nerves in sCJD and dCJD. The PrP deposits in the PNS are not correlated with clinical manifestation of peripheral neuropathy in CJD.
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Síndrome de Creutzfeldt-Jakob/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Sistema Nervioso Periférico/patología , Priones/análisis , Adulto , Anciano , Autopsia , Western Blotting , Síndrome de Creutzfeldt-Jakob/genética , Análisis Mutacional de ADN , Duramadre/trasplante , Femenino , Ganglios Espinales/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Priones/genéticaRESUMEN
The authors report an unusual family with hereditary spastic paraplegia (HSP) with frontal lobe dysfunction having the onset in the sixth decade. All the patients showed hypoperfusion in the frontal lobes and thalami on SPECT. Neuropathologic findings revealed thin corpus callosum and degeneration in the thalamic dorsomedial nuclei as well as degeneration of the corticospinal tracts. This family was likely affected by a novel form of HSP characterized by frontal lobe dysfunction caused by thalamic degeneration.
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Demencia/etiología , Lóbulo Frontal/patología , Paraplejía Espástica Hereditaria/patología , Tálamo/patología , Adulto , Edad de Inicio , Anciano , Atrofia , Demencia/patología , Progresión de la Enfermedad , Resultado Fatal , Femenino , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Gliosis/etiología , Humanos , Imagen por Resonancia Magnética , Trastornos de la Memoria/etiología , Trastornos de la Memoria/patología , Persona de Mediana Edad , Trastornos del Humor/etiología , Trastornos del Humor/patología , Tractos Piramidales/patología , Índice de Severidad de la Enfermedad , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/diagnóstico por imagen , Paraplejía Espástica Hereditaria/fisiopatología , Tálamo/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
The authors report a 75-year-old woman with atypical sporadic Creutzfeldt-Jakob disease (CJD) characterized by MM1-type prion protein (PrP) (methionine homozygosity at codon 129 in the PrP gene and type-1 protease-resistant PrP) and PrP plaques. This patient is the first case of sporadic CJD with plaque-forming MM1-type PrP, suggesting either a shared prion strain with the plaque-forming subset of dural graft-associated CJD or shared host genetic factors that are unrelated to the PrP genotype.
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Síndrome de Creutzfeldt-Jakob/diagnóstico , Placa Amiloide/patología , Priones/análisis , Anciano , Western Blotting , Encéfalo/patología , Química Encefálica , Proteínas del Líquido Cefalorraquídeo/análisis , Síndrome de Creutzfeldt-Jakob/complicaciones , Síndrome de Creutzfeldt-Jakob/patología , Electroencefalografía , Femenino , Gliosis/etiología , Gliosis/patología , Humanos , Inmunohistoquímica , Síndrome de Secreción Inadecuada de ADH/complicaciones , Síndrome de Secreción Inadecuada de ADH/diagnóstico , Imagen por Resonancia Magnética , Priones/genéticaAsunto(s)
Desinfectantes/metabolismo , Ingeniería Genética , Cloruro de Mercurio/metabolismo , Mercurio/metabolismo , Pseudomonas putida/genética , Pseudomonas putida/fisiología , Purificación del Agua/métodos , Biodegradación Ambiental , Mercurio/química , Volatilización , Eliminación de Residuos LíquidosRESUMEN
Autosomal recessive distal myopathy or Nonaka distal myopathy (NM) is characterized by its unique distribution of muscular weakness and wasting. The patients present with spared quadriceps muscles even in a late stage of the disease. The hamstring and tibialis anterior muscles are affected severely in early adulthood. We have localized the NM gene to the region between markers D9S319 and D9S276 on chromosome 9 by linkage analysis. To further refine the localization of the NM gene, we conducted homozygosity and linkage disequilibrium analysis for 14 patients from 11 NM families using 18 polymorphic markers. All of the patients from consanguineous NM families were found to be homozygous for six markers located within the region between markers D9S2178 and D9S1859. We also provided evidence for significant allelic associations between the NM region and five marker loci. Examination of the haplotype analysis identified a predominant ancestral haplotype comprising the associated alleles 199-160-154-109 (marker order: D9S2179-D9S2180-D9S2181-D9S1804), present in 60% of NM chromosomes and in 0% of parent chromosomes. On the basis of the data obtained in this study, the majority of NM chromosomes were derived from a single ancestral founder, and the NM gene is probably located within the 1.5-Mb region between markers D9S2178 and D9S1791.
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Cromosomas Humanos Par 9 , Genes Recesivos , Desequilibrio de Ligamiento , Distrofias Musculares/genética , Adulto , Alelos , Mapeo Cromosómico , Consanguinidad , Cartilla de ADN , Femenino , Marcadores Genéticos , Haplotipos/genética , Homocigoto , Humanos , Masculino , Distrofias Musculares/clasificación , Polimorfismo GenéticoRESUMEN
A convenient method for the oxidation of nucleoside phosphites into phosphates under nonbasic and nonaqueous conditions using commercially available ethyl(methyl)dioxirane has been developed. This oxidation is effective with both N-protected and N-unprotected strategies.
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Óxido de Etileno , Nucleósidos/química , Nucleótidos/química , Nucleótidos/síntesis química , Fosfitos/química , Óxido de Etileno/análogos & derivados , Indicadores y Reactivos , Estructura Molecular , Oxidación-ReducciónRESUMEN
The widespread and persistent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin elicits adaptive and adverse biological responses by inducing changes in gene transcription. Some of dioxin's effects reflect disruption of endocrine homeostasis. The aromatic hydrocarbon receptor protein, together with its heterodimerization partner, the aromatic hydrocarbon receptor nuclear translocator protein, mediates dioxin action. There are notable similarities between the mechanism of dioxin action and the mechanisms of steroid/retinoid/thyroid hormone action. Studies of dioxin action may provide insights into the regulation of hormone-responsive genes and endocrine physiology.
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Proteínas de Unión al ADN , Contaminantes Ambientales/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Dibenzodioxinas Policloradas/farmacología , Receptores de Hidrocarburo de Aril/fisiología , Teratógenos/farmacología , Animales , Translocador Nuclear del Receptor de Aril Hidrocarburo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/fisiología , Elementos de Facilitación Genéticos/genética , Elementos de Facilitación Genéticos/fisiología , Contaminantes Ambientales/efectos adversos , Contaminantes Ambientales/metabolismo , Femenino , Secuencias Hélice-Asa-Hélice , Humanos , Masculino , Ratones , Dibenzodioxinas Policloradas/efectos adversos , Dibenzodioxinas Policloradas/metabolismo , Regiones Promotoras Genéticas/genética , Regiones Promotoras Genéticas/fisiología , Salud Pública , Ratas , Teratógenos/metabolismo , Factores de Transcripción/fisiologíaRESUMEN
This report concerns a 41-year-old female case of spinal muscular atrophy (SMA) associated with vocal cord paralysis. Her parents were not consanguineous. Her maternal grandmother and younger brother were suspected of having SMA. At age 37, she first experienced gait disturbance and began to have slowly progressive dysarthria and weakness of the extremities. Neurological examination revealed that she had inspiratory stridor, dysarthria and proximal muscular weakness of the extremities. Achilles tendon reflexes were absent, while there were no pathological reflexes or sensory disturbances. She showed a waddling gait and Gowers' sign. The laboratory data indicated mild elevation of serum CK. The nerve conduction study was normal, while the electromyographic study and muscle biopsy revealed neurogenic changes. We diagnosed the case as adult onset SMA of the autosomal dominant type. Laryngoscopy revealed that the patient had vocal cord paralysis, which was predominant in abductor muscles and of the posterior paralysis type according to the categories established by Isozaki. Genetic analysis showed no mutations in the genes of the neuronal apoptosis inhibitory protein and of the survival motor neuron.
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Genes Dominantes , Atrofia Muscular Espinal/genética , Parálisis de los Pliegues Vocales/etiología , Adulto , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Femenino , Humanos , Atrofia Muscular Espinal/complicaciones , Atrofia Muscular Espinal/diagnóstico , Mutación , Proteínas del Tejido Nervioso/genética , Proteína Inhibidora de la Apoptosis Neuronal , Proteínas de Unión al ARN , Proteínas del Complejo SMN , Parálisis de los Pliegues Vocales/fisiopatologíaRESUMEN
We used mouse hepatoma (Hepa1c1c7) cells to study the role of the serine/threonine kinase Akt in the induction of GLUT1 gene expression. In order to selectively turn on the Akt kinase cascade, we expressed a hydroxytamoxifen-regulatable form of Akt (myristoylated Akt1 estrogen receptor chimera (MER-Akt1)) in the Hepa1c1c7 cells; we verified that hydroxytamoxifen stimulates MER-Akt1 activity to a similar extent as the activation of endogenous Akt by insulin. Our studies reveal that stimulation of MER-Akt1 by hydroxytamoxifen induces GLUT1 mRNA and protein accumulation to levels comparable to that induced by insulin; therefore, activation of the Akt cascade suffices to induce GLUT1 gene expression in this cell system. Furthermore, expression of a kinase-inactive Akt mutant partially inhibits the response of the GLUT1 gene to insulin. Additional studies reveal that the induction of GLUT1 mRNA by Akt and by insulin reflects increased mRNA synthesis and not decreased mRNA degradation. Our findings imply that the GLUT1 gene responds to insulin at the transcriptional level and that Akt mediates a step in the activation of GLUT1 gene expression in this system.
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Regulación de la Expresión Génica , Proteínas de Transporte de Monosacáridos/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas , Transcripción Genética , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 1 , Insulina/farmacología , Neoplasias Hepáticas Experimentales/enzimología , Neoplasias Hepáticas Experimentales/genética , Ratones , Proteínas Proto-Oncogénicas c-akt , ARN Mensajero/genética , Células Tumorales CultivadasRESUMEN
This article is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the April 1998 Experimental Biology '98 meeting in San Francisco. The presentations focused on the mechanisms of regulation of cytochrome P450 gene expression by developmental factors and by hormones and cytokines, as well as on the interplay between physiological and chemical regulation. Approaches and systems used to address these questions included conditional gene knockouts in mice, primary hepatocyte cultures, immunofluorescence imaging of cells, and cell lines stably expressing reporter gene constructs.
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Sistema Enzimático del Citocromo P-450/fisiología , Regulación Enzimológica de la Expresión Génica/fisiología , Animales , Sistema Enzimático del Citocromo P-450/biosíntesis , Sistema Enzimático del Citocromo P-450/genética , Inducción Enzimática/efectos de los fármacos , Humanos , RatonesRESUMEN
We have analyzed protein-DNA interactions in vivo at transcriptional control elements for two hypoxia-inducible genes in mouse hepatoma cells. The promoter for the phosphoglycerate kinase 1 (PGK1) gene contains an initiator element, but no TATA sequence, whereas the promoter for the glucose transporter 1 (Glut1) gene contains a TATA element but no initiator sequence. Our findings reveal hypoxia-inducible, Arnt-dependent occupancy of DNA recognition sites for hypoxia-inducible factor 1 (HIF-1) upstream of both target genes. The conserved recognition motif among the five recognition sites is 5'-CGTG-3'. The PGK1 promoter exhibits constitutive occupancy of a binding site for an unknown protein(s); however, we detect no protein-DNA interaction at the initiator element, in either uninduced or induced cells. The Glut1 promoter also exhibits constitutive protein binding; in addition, the TATA element exhibits partial occupancy in uninduced cells and increased occupancy under hypoxic conditions. We find no evidence for hypoxia-induced changes in chromatin structure of either gene. Time-course analyses of the Glut1 gene reveal a temporal relationship between occupancy of HIF-1 sites and TATA element occupancy. Our findings suggest that the promoters for both hypoxia-responsive genes constitutively maintain an accessible chromatin configuration and that HIF-1 facilitates transcription by recruiting and/or stabilizing a transcription factor(s), such as TFIID, at both promoters.
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Hipoxia de la Célula/genética , Proteínas de Unión al ADN , Elementos de Facilitación Genéticos , Regulación Enzimológica de la Expresión Génica , Proteínas de Transporte de Monosacáridos/genética , Fosfoglicerato Quinasa/genética , Regiones Promotoras Genéticas , Receptores de Hidrocarburo de Aril , Animales , Translocador Nuclear del Receptor de Aril Hidrocarburo , Secuencia de Bases , Sitios de Unión , Cartilla de ADN , Regulación Neoplásica de la Expresión Génica , Transportador de Glucosa de Tipo 1 , Neoplasias Hepáticas Experimentales/genética , Ratones , Reacción en Cadena de la Polimerasa , TATA Box , Factores de Transcripción/deficiencia , Factores de Transcripción/metabolismo , Células Tumorales CultivadasAsunto(s)
Sistema Enzimático del Citocromo P-450/genética , Proteínas de Unión al ADN/metabolismo , ADN/metabolismo , Regulación de la Expresión Génica , Animales , ADN/aislamiento & purificación , Desoxirribonucleasa I , Electroforesis en Gel de Poliacrilamida/métodos , Humanos , Reacción en Cadena de la Polimerasa/métodosRESUMEN
We have studied the transcriptional regulation of the dioxin-inducible mouse CYP1A1 gene in its native chromosomal setting. We analyzed the ability of aromatic hydrocarbon receptor (AhR) mutants and AhR chimeras to restore dioxin responsiveness to the CYP1A1 gene in AhR-defective mouse hepatoma cells. Our data reveal that transactivation domains in AhR's C-terminal half mediate occupancy of the nuclear factor 1 site and TATA box for the CYP1A1 promoter in vivo. Transactivation domains of VP16 and AhR nuclear translocator, but not Sp1, can substitute for AhR's C-terminal half in facilitating protein binding at the promoter. Our data also reveal an apparent linear relationship between promoter occupancy and CYP1A1 gene expression in chromatin. These findings provide new insights into the in vivo mechanism of transcriptional activation for an interesting mammalian gene.
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Citocromo P-450 CYP1A1/genética , Receptores de Hidrocarburo de Aril/fisiología , Animales , Translocador Nuclear del Receptor de Aril Hidrocarburo , Proteínas de Unión al ADN/fisiología , Dioxinas/farmacología , Elementos de Facilitación Genéticos/fisiología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Ratones , Regiones Promotoras Genéticas , Proteínas Recombinantes de Fusión , Factores de Transcripción/metabolismo , Activación TranscripcionalRESUMEN
We treated two cases of gastric anisakiasis presenting with severe chest pain. In both cases, there was a history of prior ingestion of raw saltwater fish. After endoscopic removal of larvae, the chest pain disappeared and never recurred. Other diseases causing chest pain were ruled out by symptoms, signs, blood tests, electrocardiography, chest radiograph, and ultrasonic examination of the heart and abdomen. Thus the chest pain was considered to be caused by gastric anisakiasis. Gastric anisakiasis should be included in the differential diagnosis of acute chest pain.
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Anisakiasis/complicaciones , Dolor en el Pecho/etiología , Gastropatías/complicaciones , Adulto , Animales , Anisakiasis/diagnóstico , Anisakiasis/parasitología , Anisakis , Dolor en el Pecho/parasitología , Femenino , Peces/parasitología , Parasitología de Alimentos , Humanos , Larva , Masculino , Persona de Mediana Edad , Gastropatías/diagnóstico , Gastropatías/parasitologíaRESUMEN
A young woman presented with mediastinal lymphadenitis and measles-like eruption. All clinical manifestations promptly responded to macrolide therapy. Serologically, current infection of Chlamydia pneumoniae was highly suspected. Evaluation of Chlamydia pneumoniae infection should be included in the diagnostic approach to mediastinal lymphadenitis.
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Infecciones por Chlamydia/diagnóstico , Chlamydophila pneumoniae , Linfadenitis/diagnóstico , Linfadenitis/microbiología , Enfermedades del Mediastino/microbiología , Adolescente , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Anticuerpos Antibacterianos/análisis , Infecciones por Chlamydia/tratamiento farmacológico , Infecciones por Chlamydia/inmunología , Exantema/complicaciones , Exantema/diagnóstico , Femenino , Humanos , Macrólidos , Enfermedades del Mediastino/diagnósticoRESUMEN
Three families with a common clinical feature of adult onset myoclonus epilepsy were studied. Onset of the myoclonus, continuously presented and intensified by movement and emotional stress, was between the 3rd and 5th decades. Generalized seizures, following worsening of the myoclonus, occurred only a few times in life. This condition was considered to be an autosomal dominant trait with a high rate of penetrance. Although the symptoms gradually worsened with age in some cases, they were not associated with dementia or cerebellar disorder, distinguishing this condition from progressive myoclonus epilepsies (PMEs). Electrophysiologically, polyspikes on the electroencephalogram (EEG), giant wave in somatosensory evoked potentials, enhanced long-loop C reflexes and a preceding wave on jerk-locked back averaging of EEG were demonstrated, suggesting that the myoclonus originated in the cerebral cortices. This is a distinct hereditary disease different from PMEs, juvenile myoclonic epilepsy or other myoclonic disorders seen in adults.