RESUMEN

BACKGROUND: Oscillatory activities observed in multiple regions are closely associated with the experience of pain. Specifically, oscillatory activities within the theta- and beta-frequency bands, observed in the left dorsolateral prefrontal cortex (DLPFC), have been implicated in pain perception among healthy individuals and those with chronic pain. However, their physiological significance remains unclear. METHODS: We explored the modulation of pain perception in healthy individuals by theta- and beta-band transcranial alternating current stimulation (tACS) over the left DLPFC and examined the relationship between the modulation effect and magnitude of the electric field elicited by tACS in the left DLPFC using computational simulation. RESULTS: Our findings revealed that both theta- and beta-tACS increased the heat pain threshold during and after stimulation. Notably, the simulated electric field magnitude in the left DLPFC exhibited an inverted U-shaped relationship with the pain modulation effect for theta-tACS. CONCLUSIONS: Our study findings suggested that there would be an optimal electric field strength to produce a high analgesic effect for theta-tACS. SIGNIFICANCE: The application of theta- and beta-tACS interventions targeting the left DLPFC might facilitate the treatment of chronic pain. Furthermore, the attainment of effective pain modulation via theta-tACS over the DLPFC warrants the use of optimal stimulus intensity.

Asunto(s)

Percepción del Dolor , Umbral del Dolor , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Masculino , Femenino , Percepción del Dolor/fisiología , Adulto , Adulto Joven , Umbral del Dolor/fisiología , Ritmo Teta/fisiología , Corteza Prefontal Dorsolateral/fisiología , Ritmo beta/fisiología , Dolor Crónico/terapia , Dolor Crónico/fisiopatología , Manejo del Dolor/métodos

RESUMEN

OBJECTIVE: RNF213 was recently reported as a susceptibility gene for moyamoya disease (MMD). Our aim was to clarify the correlation between the RNF213 genotype and MMD phenotype. METHODS: The entire coding region of the RNF213 gene was sequenced in 204 patients with MMD, and corresponding variants were checked in 62 pairs of parents, 13 mothers and 4 fathers of the patients, and 283 normal controls. Clinical information was collected. Genotype-phenotype correlations were statistically analyzed. RESULTS: The c.14576G>A variant was identified in 95.1% of patients with familial MMD, 79.2% of patients with sporadic MMD, and 1.8% of controls, thus confirming its association with MMD, with an odds ratio of 259 and p < 0.001 for either heterozygotes or homozygotes. Homozygous c.14576G>A was observed in 15 patients but not in the controls and unaffected parents. The incidence rate for homozygotes was calculated to be >78%. Homozygotes had a significantly earlier age at onset compared with heterozygotes or wild types (median age at onset 3, 7, and 8 years, respectively). Of homozygotes, 60% were diagnosed with MMD before age 4, and all had infarctions as the first symptom. Infarctions at initial presentation and involvement of posterior cerebral arteries, both known as poor prognostic factors for MMD, were of significantly higher frequency in homozygotes than in heterozygotes and wild types. Variants other than c.14576G>A were not associated with clinical phenotypes. CONCLUSIONS: The homozygous c.14576G>A variant in RNF213 could be a good DNA biomarker for predicting the severe type of MMD, for which early medical/surgical intervention is recommended, and may provide a better monitoring and prevention strategy.

Asunto(s)

Enfermedad de Moyamoya/genética , Ubiquitina-Proteína Ligasas/genética , Adenosina Trifosfatasas , Adolescente , Adulto , Edad de Inicio , Biomarcadores , Infarto Cerebral/etiología , Niño , Preescolar , ADN/genética , Análisis Mutacional de ADN , Epilepsia/complicaciones , Familia , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Genotipo , Homocigoto , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/psicología , Masculino , Persona de Mediana Edad , Enfermedad de Moyamoya/patología , Fenotipo , Arteria Cerebral Posterior/patología , Valor Predictivo de las Pruebas , Caracteres Sexuales , Adulto Joven

RESUMEN

BACKGROUND: The TFII-I is a multifunctional transcriptional factor known to bind specifically to several DNA sequence elements and to mediate growth factor signalling. A microdeletion at the chromosomal location 7q11.23 encoding TFII-I and the related family of transcription factors may result in the onset of Williams-Beuren syndrome, an autosomal dominant genetic disorder characterised by a unique cognitive profile, diabetes, hypertension, anxiety, and craniofacial defects. Hereditary breast and ovarian cancer susceptibility gene product BRCA1 has been shown to serve as a positive regulator of SIRT1 expression by binding to the promoter region of SIRT1, but cross talk between BRCA1 and TFII-I has not been investigated to date. METHODS: A physical interaction between TFII-I and BRCA1 was explored. To determine pathophysiological function of TFII-I, its role as a transcriptional cofactor for BRCA1 was investigated. RESULTS: We found a physical interaction between the carboxyl terminus of TFII-I and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous TFII-I and BRCA1 form a complex in nuclei of intact cells and formation of irradiation-induced nuclear foci was observed. We also showed that the expression of TFII-I stimulates the transcriptional activation function of BRCT by a transient expression assay. The expression of TFII-I also enhanced the transcriptional activation of the SIRT1 promoter mediated by full-length BRCA1. CONCLUSION: These results revealed the intrinsic mechanism that TFII-I may modulate the cellular functions of BRCA1, and provide important implications to understand the development of breast cancer.

Asunto(s)

Proteína BRCA1/fisiología , Factores de Transcripción TFII/fisiología , Animales , Proteína BRCA1/metabolismo , Células COS , Línea Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/patología , Chlorocebus aethiops , Daño del ADN/fisiología , Regulación Neoplásica de la Expresión Génica , Células HeLa , Humanos , Unión Proteica , Sirtuina 1/genética , Sirtuina 1/metabolismo , Transactivadores/metabolismo , Transactivadores/fisiología , Factores de Transcripción TFII/metabolismo , Activación Transcripcional/fisiología

RESUMEN

The cell polarity regulator, human Scribble (hScrib), is a potential tumour suppressor whose loss is a frequent event in late-stage cancer development. Little is yet known about the mode of action of hScrib, although recent reports suggest its role in the regulation of cell signalling. In this study we show that hScrib is a direct regulator of extracellular signal-regulated kinase (ERK). In human keratinocytes, loss of hScrib results in elevated phospho-ERK levels and concomitant increased nuclear translocation of phospho-ERK. We also show that hScrib interacts with ERK through two well-conserved kinase interaction motif (KIM) docking sites, both of which are also required for ERK-induced phosphorylation of hScrib on two distinct residues. Although wild-type hScrib can downregulate activation of ERK and oncogenic Ras co-transforming activity, an hScrib mutant that lacks the carboxy terminal KIM docking site has no such effects. These results provide a clear mechanistic explanation of how hScrib can regulate ERK signalling and begin to explain how loss of hScrib during cancer development can contribute to disease progression.

Asunto(s)

Polaridad Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas de la Membrana/fisiología , Proteínas Supresoras de Tumor/fisiología , Núcleo Celular/enzimología , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Activación Enzimática , Humanos , Fosforilación

RESUMEN

BACKGROUND: DBC1/KIAA1967 (deleted in breast cancer 1) is a putative tumour-suppressor gene cloned from a heterozygously deleted region in breast cancer specimens. Caspase-dependent processing of DBC1 promotes apoptosis, and depletion of endogenous DBC1 negatively regulates p53-dependent apoptosis through its specific inhibition of SIRT1. Hereditary breast and ovarian cancer susceptibility gene product BRCA1, by binding to the promoter region of SIRT1, is a positive regulator of SIRT1 expression. METHODS: A physical interaction between DBC1 and BRCA1 was investigated both in vivo and in vitro. To determine the pathophysiological significance of DBC1, its role as a transcriptional factor was studied. RESULTS: We found a physical interaction between the amino terminus of DBC1 and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous DBC1 and BRCA1 form a complex in the nucleus of intact cells, which is exported to the cytoplasm during ultraviolet-induced apoptosis. We also showed that the expression of DBC1 represses the transcriptional activation function of BRCT by a transient expression assay. The expression of DBC1 also inhibits the transactivation of the SIRT1 promoter mediated by full-length BRCA1. CONCLUSION: These results revealed that DBC1 may modulate the cellular functions of BRCA1 and have important implications in the understanding of carcinogenesis in breast tissue.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/fisiología , Proteína BRCA1/metabolismo , Regulación Neoplásica de la Expresión Génica , Activación Transcripcional , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Apoptosis/genética , Proteína BRCA1/química , Proteína BRCA1/fisiología , Células Cultivadas , Células HeLa , Humanos , Unión Proteica , Estructura Terciaria de Proteína/fisiología , Proteínas Represoras/metabolismo , Proteínas Represoras/fisiología , Sirtuina 1/genética , Distribución Tisular , Activación Transcripcional/genética

RESUMEN

Human papillomaviruses (HPVs) are the causative agents of a number of human cancers, of which cervical cancer is the most important. This occurs following persistent infection with a limited number of viral subtypes and is characterized by continued expression of the viral E6 and E7 oncoproteins. A unique characteristic of the cancer-causing HPV types is the presence of a PDZ recognition motif on the carboxy terminus of the E6 oncoprotein. Through this motif, E6 directs the proteasome-mediated degradation of cellular proteins involved in the regulation of cell polarity and in cell proliferation control. These include components of the Scrib and Par polarity complexes, as well as a number of other PDZ domain-containing substrates. Thus, PVs are now providing novel insights into the functioning of many of these cellular proteins, and into which of these functions, in particular, are relevant for maintaining normal cellular homeostasis. In this review, we discuss the biological consequences of papillomaviral targeting of these cell polarity regulators, both with respect to the viral life cycle and, most importantly, to the development of HPV-induced malignancy.

Asunto(s)

Alphapapillomavirus/fisiología , Carcinoma/etiología , Polaridad Celular/fisiología , Infecciones por Papillomavirus/complicaciones , Neoplasias del Cuello Uterino/etiología , Secuencias de Aminoácidos , Carcinoma/genética , Polaridad Celular/genética , Femenino , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/fisiología , Modelos Biológicos , Dominios PDZ/fisiología , Neoplasias del Cuello Uterino/genética , Acoplamiento Viral

Asunto(s)

Pueblo Asiatico/genética , Enfermedades de los Ganglios Basales/diagnóstico , Enfermedades de los Ganglios Basales/genética , Ferritinas/genética , Duplicación de Gen , Adulto , Secuencia de Aminoácidos , Apoferritinas , Enfermedades de los Ganglios Basales/metabolismo , Secuencia de Bases , Exones/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje

Asunto(s)

Anticuerpos Monoclonales/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/inducido químicamente , Receptores de Interleucina-6/antagonistas & inhibidores , Anticuerpos Monoclonales Humanizados , Enfermedad Crónica , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , Infecciones Oportunistas/inducido químicamente

RESUMEN

A 35-year-old woman, gravida 1, para 1, underwent cesarean section in her 39th week of pregnancy. At the time of operation, multiple retroperitoneal tumors were found. Postoperative computed tomography and magnetic resonance imaging showed multiple solid tumors, each approximately 3-5 cm, in the right pelvic retroperitoneal space. Total resection of the tumors was performed without any macroscopic residual. A systematic workup for the primary tumor from which the retroperitoneal tumors may have metastasized failed to demonstrate any responsible tumor. We therefore assumed it to be a primary retroperitoneal tumor. The histopathologic features of the tumors were consistent with small-cell carcinoma. Two months postoperatively, recurrent tumors in the right inguinal and common iliac regions were detected. Since chemotherapy with irinotecan hydrochloride or paclitaxel did not produce any beneficial effect, a second tumor reduction surgery was performed 8 months after the initial operation. Four months after the second operation, a third operation including total hysterectomy, bilateral salpingo-oophorectomy, and tumor resection in the contralateral iliac region were done. Afterward, a new recurrent tumor appeared along the aorta up to the left supraclavicular node. The patient died 19 months after the first operation.

Asunto(s)

Carcinoma de Células Pequeñas/diagnóstico , Complicaciones Neoplásicas del Embarazo/diagnóstico , Neoplasias Retroperitoneales/diagnóstico , Adulto , Antineoplásicos/uso terapéutico , Carcinoma de Células Pequeñas/terapia , Cesárea , Resultado Fatal , Femenino , Procedimientos Quirúrgicos Ginecológicos , Humanos , Hallazgos Incidentales , Imagen por Resonancia Magnética , Embarazo , Complicaciones Neoplásicas del Embarazo/terapia , Recurrencia , Reoperación , Neoplasias Retroperitoneales/terapia

RESUMEN

The DNA mismatch repair gene is a key regulator in the elimination of base-base mismatches and insertion/deletion loops (IDLs). Human MutS homologue 2 (hMSH2), originally identified as a human homologue of the bacterial MutS, is a tumour suppressor gene frequently mutated in hereditary non-polyposis colorectal cancer. Hereditary non-polyposis colorectal cancer is characterised by the early onset of colorectal cancer and the development of extracolonic cancers such as endometrial, ovarian, and urological cancers. Oestrogen receptor (ER) alpha and beta are members of a nuclear receptor (NR) superfamily. Ligand-dependent transcription of ER is regulated by the p160 steroid receptor coactivator family, the thyroid hormone receptor-associated proteins/the vitamin D receptor-interacting proteins (TRAP/DRIP) mediator complex, and the TATA box-binding protein (TBP)-free TBP associated factor complex (TFTC) type histone acetyltransferase complex. Here, we report the interaction between ER alpha/beta and hMSH2. Immunoprecipitation and glutathione-S-transferase pull-down assay revealed that ER alpha and hMSH2 interacted in a ligand-dependent manner, whereas ER beta and hMSH2 interacted in a ligand-independent manner. Oestrogen receptor alpha/beta bound to hMSH2 through the hMSH3/hMSH6 interaction domain of hMSH2. In a transient expression assay, hMSH2 potentiated the transactivation function of liganded ER alpha, but not that of ER beta. These results suggest that hMSH2 may play an important role as a putative coactivator in ER alpha dependent gene expression.

Asunto(s)

Disparidad de Par Base/genética , Reparación del ADN/genética , Proteínas de Unión al ADN/genética , Receptor alfa de Estrógeno/genética , Proteínas Proto-Oncogénicas/genética , Neoplasias de la Mama/genética , Línea Celular Tumoral , Mapeo Cromosómico , Neoplasias Endometriales/genética , Receptor beta de Estrógeno/genética , Femenino , Expresión Génica , Genes Supresores de Tumor , Humanos , Proteína 2 Homóloga a MutS , Activación Transcripcional

RESUMEN

Abstract Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown origin. Acute respiratory distress syndrome (ARDS) is a rare complication of AOSD, with only nine cases having been reported in the literature. Here, we describe two cases of AOSD complicated with ARDS that were successfully treated with immunosuppressive therapy, including corticosteroids. Although ARDS is a life-threatening complication in AOSD, early commencement of high-dose corticosteroids and mechanical ventilation improve the prognosis.

RESUMEN

Venom proteins from the dorsal spine of two scorpionfish, Hypodytes rubripinnis and Synanceia verrucosa were assayed for mitogenicity and cytotoxicity. The two venoms had both mitogenic and cytotoxic activity on murine splenocytes and murine P388 leukemic cells. In H. rubripinnis, the second gel chromatographic fraction showed cytotoxic activity on P388 leukemic cells. On native PAGE, the glycoprotein isolated by concavalin A sepharose chromatography appeared to have a molecular mass of 110 kDa. In addition, two D-galactose-binding lectins (SUL-I and SUL-II) and a heparin-binding lectin (TGL-I) were purified from the globiferous pedicellariae of the toxopneustid sea urchins, Toxopneustes pileolus and Tripneustes gratilla, respectively. SUL-I (Nakagawa et al., 1999a) had mitogenic activity and cytotoxic activity but SUL-II and TGL-I did not. SUL-I did not show sequence homology to SUL-II. A hemolytic lectin with a molecular mass of 29 kDa was isolated from the coelomic fluid of T. gratilla. The hemolytic activity of the lectin was dependent on Ca2+ concentration and inhibited by lactose. The present results suggest that some species of scorpionfish and sea urchins may be novel sources for biologically active substances such as anti-tumor compounds or new lectins.

Asunto(s)

Peces Venenosos , Lectinas/farmacología , Toxinas Marinas/farmacología , Mitógenos/farmacología , Erizos de Mar/química , Aglutinación , Secuencia de Aminoácidos , Animales , Supervivencia Celular/efectos de los fármacos , Cromatografía en Gel , Electroforesis en Gel de Poliacrilamida , Venenos de los Peces/aislamiento & purificación , Venenos de los Peces/farmacología , Lectinas/química , Lectinas/aislamiento & purificación , Toxinas Marinas/aislamiento & purificación , Ratones , Mitógenos/aislamiento & purificación , Datos de Secuencia Molecular , Bazo/citología , Bazo/efectos de los fármacos , Células Tumorales Cultivadas

RESUMEN

AIMS/HYPOTHESIS: A point mutation of mitochondrial DNA at nucleotide number 3243 A to G is responsible for both the major genetic aetiologies of the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and mitochondrial diabetes. Otherwise, this mutation is also reported to occur as an acquired somatic mutation, possibly due to oxidative stress. Since diabetes can cause severe oxidative stress, we hypothesize that the accumulation of the somatic 3243 A to G mutation in mitochondrial DNA can be accelerated by diabetes. METHODS: DNA was extracted from blood samples of 290 non-diabetic healthy subjects (age 20-60) including 98 newborn infants and from 383 patients with Type II (non-insulin-dependent) diabetes mellitus (age 18-80). The extent of somatic 3243 A to G mutation to total mitochondrial DNA was detected by real-time PCR using the TaqMan Probe. RESULTS: Whereas the level of the 3243 A to G mutation was negligible in the newborn group, it was increased in healthy subjects who were 20 to 29 and 41 to 60 years of age, suggesting that this mutation was somatic. In the diabetic patients the mutation rate increased along with age and the duration of diabetes. In the middle-aged group (age 41-60), the 3243 A to G mutation accumulates fourfold higher in the diabetic patients than the healthy subjects. Moreover, multiple regression analysis showed that the most critical factor associated with this mutation in diabetic patients was the duration of diabetes. CONCLUSION/INTERPRETATION: Diabetes accelerates the accumulation of the somatic 3243 A to G mutation in mitochondrial DNA, which can accelerate the ageing process. This somatic mutation could possibly be a new marker for estimating the duration of diabetes.

Asunto(s)

ADN Mitocondrial/genética , ADN/sangre , Diabetes Mellitus Tipo 2/genética , Mutación Puntual , Adenina , Adolescente , Adulto , Edad de Inicio , Anciano , Secuencia de Bases , Índice de Masa Corporal , ADN/genética , Cartilla de ADN , Diabetes Mellitus Tipo 2/sangre , Femenino , Guanina , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , Valores de Referencia

RESUMEN

Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce inflammatory cytokines and chemokines. The expressed chemokines are thought to be involved in the migration of inflammatory cells into the synovium. In this study we show that CCL2/monocyte chemotactic protein-1, CCL5/RANTES, and CXCL12/stromal cell-derived factor-1 enhanced IL-6 and IL-8 production by fibroblast-like synoviocytes (FLS) from patients with RA, and their corresponding receptors, CCR2, CCR5, and CXCR4, respectively, were expressed by RA FLS. The chemokines stimulated RA FLS more effectively than skin fibroblasts. Culture with CCL2 enhanced phosphorylation of extracellular signal-related kinase 1 (ERK1) and ERK2, but not phosphorylation of p38 or Src. Moreover, activation of ERK1/2 was inhibited by pertussis toxin, a G(i)-coupled protein inhibitor, and RS-504393, CCR2 antagonist, suggesting that ERK1/2 was activated by CCL2 via CCR2 and G(i)-coupled protein. On the other hand, CCL2, CCL5, and CXCL12 were expressed on RA FLS, and their production was regulated by TNF-alpha, IL-1beta, and TGF-beta1. Our results indicate that the chemokines not only play a role in inflammatory cell migration, but are also involved in the activation of FLS in RA synovium, possibly in an autocrine or paracrine manner.

Asunto(s)

Artritis Reumatoide/inmunología , Quimiocina CCL2/fisiología , Quimiocina CCL5/fisiología , Quimiocinas CXC/fisiología , Interleucina-6/biosíntesis , Interleucina-8/biosíntesis , Membrana Sinovial/metabolismo , Quimiocina CXCL12 , Activación Enzimática , Fibroblastos/metabolismo , Humanos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Receptores de Quimiocina/análisis , Receptores de Quimiocina/biosíntesis , Membrana Sinovial/citología

RESUMEN

A 20-year-old man was admitted to a hospital complaining a slight fever lasting for 3 months associated with a dull headache and weight loss. A tumor was found in the nasopharynx of which biopsy specimen revealed granulomas with Langhans' giant cells. He was given antituberculous agents without symptomatic improvement, and transferred to our hospital. Serum levels of soluble IL-2 receptor and lysozyme were increased, and a significant uptake was observed by Ga scintigraphy at the nasopharynx and bilateral hilar lymphnodes. Furthermore, spinal fluid contained increased number of mononuclear cells, and T2-weighted MRI scans showed an enhanced lesion at the pituitary stalk. The specimen of both TBLB and repeated biopsy of the nasopharyngeal tumor showed granulomas without caseous necrosis. Taken together with these findings, a diagnosis of sarcoidosis with CNS involvement was finally made, and he made a favorable progress by treatment with prednisolone. This is an unique case which emphasizes importance of differential diagnosis of nasopharyngeal tumors with neurological manifestations in the clinicalsetting of rheumatology.

Asunto(s)

Enfermedades del Sistema Nervioso Central/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Sarcoidosis/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Tuberculosis/diagnóstico

RESUMEN

A novel spatial light modulator (SLM) made of an array of fused-silica plates was developed for the purpose of feedback control for intense femtosecond laser pulses over a wide spectral range. Dispersion compensation for 20-fs pulses from a Ti:sapphire oscillator was successfully demonstrated using the SLM with an adaptive feedback control system. The SLM was also applied to the output pulses from a Ti:sapphire amplifier for compensation of material.

RESUMEN

To assist genetic research into Cryptomeria japonica, which is one of the most important forest tree species in Japan, expressed sequence tag (EST) analysis was carried out. The cDNA clones were isolated from a library derived from inner bark tissues. Partial sequences were obtained from 2231 clones, representing 1398 unique transcripts. Putative functions were assigned to 1583 clones, which represented 882 unique transcripts, by a Blast algorithm. Homology analysis suggested that ESTs related to cell wall formation represented about 3% of the clones. Transcripts of plant stress response genes were also abundant in the inner bark library, especially genes involved in wounding and drought responses. This indicates that the stress response systems of this tree species are similar to those of other plants, and that these systems are highly conserved among plant species. The remaining 648 clones, which represented 516 unique transcripts, did not show any significant homology to known sequences in the databases searched: these are expected to represent genes specific to Cryptomeria and, possibly, to related species.

Asunto(s)

Cycadopsida/genética , Etiquetas de Secuencia Expresada , ADN Complementario/química , ADN Complementario/genética , Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas/genética , Genes de Plantas/fisiología , Datos de Secuencia Molecular , Análisis de Secuencia de ADN

RESUMEN

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) deficiency is caused by a mutant allele in the Mongoloids. To examine whether genetic constitutions affecting aldehyde metabolism influence the risk for late-onset Alzheimer's disease (LOAD), we performed a case-control study in the Japanese population on the deficiency in ALDH2 caused by the dominant-negative mutant allele of the ALDH2 gene (ALDH2*2). In a comparison of 447 patients with sex, age, and region matched nondemented controls, the genotype frequency carrying the ALDH2*2 allele was significantly higher in the patients than in the controls (48.1% vs 37.4%, P = 0.001). Logistic regression analysis indicates that carriage of the ALDH2*2 allele is an independent risk for LOAD of the epsilon4 allele of the apolipoprotein E gene (APOE-epsilon4) (P = 0.002). Moreover, the odds ratio for LOAD in carriers of the ALDH2*2 allele was almost twice that in noncarriers, irrespective of status with regard to the APOE-epsilon4 allele. Among patients homozygous for the APOE-epsilon4 allele, age at onset of LOAD was significantly lower in those with than without the ALDH2*2 allele. In addition, dosage of the ALDH2*2 allele significantly affected age at onset of patients homozygous for the APOE-epsilon4 allele. These results indicate that the ALDH2 deficiency is a risk for LOAD, synergistically acting with the APOE-epsilon4 allele.

Asunto(s)

Aldehído Deshidrogenasa/deficiencia , Aldehído Deshidrogenasa/genética , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Predisposición Genética a la Enfermedad/genética , Mitocondrias/enzimología , Edad de Inicio , Anciano , Anciano de 80 o más Años , Aldehído Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa Mitocondrial , Alelos , Enfermedad de Alzheimer/enzimología , Apolipoproteína E4 , Apolipoproteínas E/genética , Estudios de Casos y Controles , Femenino , Dosificación de Gen , Frecuencia de los Genes/genética , Genes Dominantes/genética , Genotipo , Humanos , Japón/epidemiología , Modelos Logísticos , Masculino , Mitocondrias/genética , Oportunidad Relativa

RESUMEN

The sequence divergence of chloroplast rbcL, matK, trnV intron, and rpl20-rps18 spacer regions was analyzed among 32 Pinus species and representatives of six other genera in Pinaceae. The total aligned sequence length is 3570 bp. Of the four sequences examined, matK evolved much faster than rbcL in Pinus and in other Pinaceae genera. The two noncoding regions did not show more divergence than the two coding regions, especially within each Pinus subgenus. Phylogenetic analyses based on these four sequences gave consistent results and strongly supported the monophyly hypothesis for the genus Pinus and its two recognized subgenera. Pinus krempfii, the two-flat-needle pine endemic to Vietnam, was placed in subgen. Strobus and showed closer affinity to subsect. Gerardianae. The ancient character of sect. Parrya is further confirmed. However, monophyly of the sect. Parrya is not supported by our data. Among the Eurasian pines of subgen. Pinus, Mediterranean pines formed one clade and the Asian members of subsect. Sylvestres formed another. The Himalayan P. roxburghii showed considerable divergence from all the other hard pines from both regions. Pinus merkusii was distinctly separated from all the Asian members of subsect. Sylvestres. The implications of our results for Pinus classification are discussed.

Asunto(s)

Artritis Reumatoide/terapia , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Genes p16 , Terapia Genética/métodos , Animales , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Modelos Animales de Enfermedad , Ratones , Ratas