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1.
J Prev Alzheimers Dis ; 9(2): 331-337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35543007

RESUMO

BACKGROUND: Matrix metalloproteinase 9 (MMP-9) has been reported to be correlated with declines in hippocampal volume and cognitive function in ApoE4-positive MCI patients. OBJECTIVES: The present study was aimed to investigate the effects of plasma matrix MMP-9 on the conversion risk between mild cognitive impairment (MCI) patients with and without ApoE4. DESIGN AND SETTING: Retrospective observational study using the data extracted from the Alzheimer's Disease Neuroimaging Initiative database. PARTICIPANTS: We included 211 ApoE4-positive MCI subjects (ApoE4+ MCI) and 184 ApoE4-negative MCI subjects (ApoE4- MCI). MEASUREMENTS: We obtained demographic and data including plasma MMP-9 levels at baseline and longitudinal changes in Clinical Dementia Rating (CDR) up to 15 years. We compared conversion rates between ApoE4+ MCI and ApoE4- MCI by the Log-rank test and calculated the hazard ratio (HR) for covariates including age, sex, educational attainment, drinking and smoking histories, medications, and plasma MMP-9 levels using a multiple Cox regression analysis of ApoE4+ MCI and ApoE4- MCI. RESULTS: No significant differences were observed in baseline plasma MMP-9 levels between ApoE4+ MCI and ApoE4- MCI. High plasma MMP-9 levels increased the conversion risk significantly more than low plasma MMP-9 levels (HR, 2.46 [95% CI, 1.31-4.48]) and middle plasma MMP-9 levels (HR, 1.67 [95% CI, 1.04-2.65]) in ApoE4+ MCI, but not in ApoE4- MCI. CONCLUSION: Plasma MMP-9 would be the risk of the future conversion to dementia in ApoE4+ MCI.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Progressão da Doença , Humanos , Metaloproteinase 9 da Matriz , Neuroimagem
2.
Int J Obes (Lond) ; 41(12): 1790-1797, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28757640

RESUMO

BACKGROUND: Neuromedin U (NMU) is a neuropeptide with various physiological functions, including regulation of smooth-muscle contraction, blood pressure, stress responses and feeding behaviors. NMU activates two distinct receptors, NMUR1 and NMUR2, which are predominantly expressed in peripheral tissues and the central nervous system (CNS), respectively. It is reported that the NMU signaling system regulates food intake (FI) and body weight (BW) via NMUR2, suggesting that an NMUR2 agonist exhibiting anorectic effects would be a potential therapy for obesity. METHODS: Antiobesity effects of NMUR2 activation were assessed using a recently developed, novel NMUR2-selective agonist, NMU-7005 (a polyethylene glycolated octapeptide). Here we assessed cumulative FI and BW loss after peripheral administration of NMU-7005 in NMUR2 knockout and diet-induced obese mice. To gain mechanistic insights, we performed immunohistochemical analysis of c-Fos-like protein expression in the brain. RESULTS: We found that NMU-7005 was a NMUR2-selective agonist with little activity toward NMUR1. The anorectic effect of NMU-7005 was completely abrogated in NMUR2 knockout mice. Repeated subcutaneous administration of NMU-7005 showed a potent antiobesity effect with FI inhibition (P<0.025) in diet-induced obese mice. NMU-7005 in combination with the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide showed an additive antiobesity effect, suggesting that NMUR2-mediated anorectic action is different from that of GLP-1R agonists. NMU-7005 also elicited a minimal conditioned taste-aversive effect, while the effect of liraglutide was significant. As c-Fos expression was upregulated in the hypothalamus and the medulla oblongata in NMU-7005-administered mice, the pharmacological effects of NMU-7005 appeared to be mediated via activation of the CNS. CONCLUSION: Our results demonstrated that a novel NMUR2-selective agonist, NMU-7005, is a beneficial tool for the elucidation of NMUR2-mediated physiological functions, which is a promising therapeutic strategy for treating obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Liraglutida/farmacologia , Neuropeptídeos/farmacologia , Obesidade/tratamento farmacológico , Receptores de Neurotransmissores/agonistas , Animais , Modelos Animais de Doenças , Comportamento Alimentar , Imuno-Histoquímica , Camundongos , Camundongos Obesos
3.
J Perinatol ; 35(11): 965-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26355942

RESUMO

OBJECTIVE: The aim of this study was to identify the best sedation/analgesia protocol for laser photocoagulation (PC) of retinopathy of prematurity (ROP). STUDY DESIGN: This multicenter observational study included five hospitals, each using a specific sedation/analgesia protocol: local anesthesia with oxybuprocaine hydrochloride (Group L); intravenous pentazocine (Group P); intravenous fentanyl (Group F); air, oxygen and sevoflurane (AOS) inhalation (Group I). The groups were compared for pain responses, vital signs and adverse events. RESULTS: Heart rates and systemic blood pressures were elevated by PC in Groups L and P and Groups L, P and F, respectively. Moreover, poor analgesic efficacy was recognized in Groups L, P and F. In contrast, Group I experienced hypothermia, enteral feeding intolerance and apnea more frequently. CONCLUSION: From the viewpoint of sedation/pain relief, AOS anesthesia should be the best protocol. However, considering all the various factors together, the most reasonable one can be varied based on the patient's condition and hospital.


Assuntos
Sedação Consciente/métodos , Recém-Nascido Prematuro , Fotocoagulação/métodos , Medição da Dor , Retinopatia da Prematuridade/cirurgia , Administração por Inalação , Estudos de Coortes , Feminino , Fentanila/administração & dosagem , Humanos , Recém-Nascido , Infusões Intravenosas , Japão , Terapia a Laser/métodos , Masculino , Éteres Metílicos/administração & dosagem , Pentazocina/administração & dosagem , Estudos Prospectivos , Retinopatia da Prematuridade/diagnóstico , Medição de Risco , Índice de Gravidade de Doença , Sevoflurano , Resultado do Tratamento
4.
Brain Struct Funct ; 218(4): 951-68, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22782432

RESUMO

Based on high-resolution diffusion tensor magnetic resonance imaging (DTI) tractographic analyses in 39 healthy adult subjects, we derived patterns of connections and measures of volume and biophysical parameters, such as fractional anisotropy (FA) for the human middle longitudinal fascicle (MdLF). Compared to previous studies, we found that the cortical connections of the MdLF in humans appear to go beyond the superior temporal (STG) and angular (AG) gyri, extending to the temporal pole (TP), superior parietal lobule (SPL), supramarginal gyrus, precuneus and the occipital lobe (including the cuneus and lateral occipital areas). Importantly, the MdLF showed a striking lateralized pattern with predominant connections between the TP, STG and AG on the left and TP, STG and SPL on the right hemisphere. In light of the results of the present study, and of the known functional role of the cortical areas interconnected by the MdLF, we suggested that this fiber pathway might be related to language, high order auditory association, visuospatial and attention functions.


Assuntos
Vias Neurais/anatomia & histologia , Lobo Parietal/anatomia & histologia , Lobo Temporal/anatomia & histologia , Adolescente , Adulto , Anisotropia , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Schizophr Res ; 141(1): 35-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22863550

RESUMO

Individuals with 22q11.2 deletion syndrome (22q11.2DS) evince a 30% incidence of schizophrenia. We compared the white matter (WM) of 22q11.2DS patients without schizophrenia to a group of matched healthy controls using Tract-Based-Spatial-Statistics (TBSS). We found localized reduction of Fractional Anisotropy (FA) and Axial Diffusivity (AD; measure of axonal integrity) in WM underlying the left parietal lobe. No changes in Radial Diffusivity (RD; measure of myelin integrity) were observed. Of note, studies in chronic schizophrenia patients report reduced FA, no changes in AD, and increases in RD in WM. Our findings suggest different WM microstructural pathology in 22q11.2DS than in patients with schizophrenia.


Assuntos
Encéfalo/patologia , Síndrome de DiGeorge/patologia , Fibras Nervosas Mielinizadas/patologia , Adolescente , Adulto , Anisotropia , Mapeamento Encefálico , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Projetos Piloto , Escalas de Graduação Psiquiátrica , Adulto Jovem
6.
Scand J Rheumatol ; 41(2): 103-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22217397

RESUMO

OBJECTIVES: Exposure to reactive oxygen species (ROS) through cigarette smoking is thought to contribute to the development of systemic lupus erythematosus (SLE). Metabolic enzymes are involved in ROS production. The aim of this study was to evaluate the modifying effect of metabolic polymorphisms on the association of cigarette smoking with SLE risk in a Japanese population. METHODS: We investigated the relationship of the cytochrome P450 (CYP) 1A1 rs4646903 and glutathione S-transferase (GST) M1 deletion polymorphisms to SLE risk with attention to interaction with cigarette smoking among 151 SLE cases and 421 controls in female Japanese subjects. Unconditional logistic regression was used to compute the odds ratios (ORs) and their 95% confidence intervals (CIs), with adjustments for several covariates. RESULTS: Smokers with the CC genotype of CYP1A1 rs4646903 were significantly associated with increased risk of SLE (OR 9.72, 95% CI 2.73-34.6). Similarly, smokers with the combined CYP1A1 rs4646903/GSTM1 'at-risk' genotype were significantly associated with increased risk of SLE (OR 17.5, 95% CI 3.20-95.9). More than 60% of the excess risk for SLE in smokers with the CC genotype and smokers with the combined 'at-risk' genotype was due to an additive interaction. A lack of association of the GSTM1 genotypes with smoking was observed. CONCLUSIONS: Our results suggest that a combination of smoking and either the CYP1A1 rs4646903 genotype or the combined metabolic genotype plays an important role in SLE susceptibility in our Japanese population. Additional studies are warranted to confirm the metabolic polymorphism-smoking interaction suggested in the present study.


Assuntos
Citocromo P-450 CYP1A1/genética , Predisposição Genética para Doença , Glutationa Transferase/genética , Lúpus Eritematoso Sistêmico/genética , Fumar/efeitos adversos , Tabagismo/genética , Adulto , Comorbidade , Feminino , Deleção de Genes , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , Tabagismo/diagnóstico , Tabagismo/epidemiologia
7.
Diabetes Obes Metab ; 13(9): 806-13, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21492364

RESUMO

AIM: To examine the efficacy, safety and tolerability of rivoglitazone, a novel thiazolidinedione (TZD), and explore its effects on glucose and lipid control compared to placebo and pioglitazone in Chinese type 2 diabetic patients who are treatment naÏve or treated with a single oral blood glucose-lowering drug. METHODS: This was a double-blind, randomized, placebo- and active-controlled study. A total of 287 Chinese type 2 diabetic patients with suboptimal glycaemic control (defined as HbA1c ≥6.5 to <10% and fasting plasma glucose ≥7 to ≤15 mmol/l) were enrolled. One hundred and seventy-four eligible patients were randomized into one of the five treatment arms for 12 weeks: placebo, pioglitazone 30 mg daily, rivoglitazone of dose 0.5, 1.0 or 1.5 mg daily. In a full set analysis, we used analysis of covariance to compare the primary endpoint defined as change in HbA1c from baseline to week 12/last observation carried forward in the rivoglitazone group at each dose level with the placebo group. RESULTS: Changes in HbA1c were -0.11% in the 0.5-mg group; -0.22% in the 1-mg group and -0.17% in the 1.5-mg rivoglitazone group; -0.06% in the 30-mg pioglitazone group and 0.61% in the placebo group. Compared to placebo, changes were significant in all active treatment groups (all p < 0.05). Increase in high-density lipoprotein cholesterol and decrease in triglyceride were observed in the rivoglitazone 1 and 1.5 mg groups, respectively, compared to placebo from baseline to week 12 (p < 0.05). Drug-related oedema was reported in eight patients (7.7%) in all rivoglitazone groups compared to six patients (16.2%) in the pioglitazone group and one patient (3.0%) in the placebo group. CONCLUSIONS: Rivoglitazone is an efficacious, safe and well-tolerated TZD which improved glycaemic control in Chinese type 2 diabetic patients up to 3 months.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , PPAR gama/agonistas , Tiazolidinedionas/administração & dosagem , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Método Duplo-Cego , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Pioglitazona , Tiazolidinedionas/farmacologia , Resultado do Tratamento , Adulto Jovem
8.
J Evol Biol ; 23(11): 2377-84, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20825549

RESUMO

Development is left-right reversed between dextral and sinistral morphs of snails. In sympatry, they share the same gene pool, including polygenes for shell shape. Nevertheless, their shell shapes are not the mirror images of each other. This triggered a debate between hypotheses that argue either for a developmental constraint or for zygotic pleiotropic effects of the polarity gene. We found that dextrals can be wider or narrower than sinistrals depending on the population, contrary to the prediction of invariable deviation under a developmental constraint. If the pleiotropy is solely responsible instead, the mean shape of each morph should change, depending on the frequency of polarity genotype. Our simulations of this mean shape change under zygotic pleiotropy, however, show that the direction of interchiral difference remains the same regardless of genotype frequency. Our results suggest the presence of genetic variation among populations that changes the maternal or zygotic pleiotropic effect of the polarity gene.


Assuntos
Estruturas Animais/anatomia & histologia , Padronização Corporal/fisiologia , Pleiotropia Genética/fisiologia , Padrões de Herança/genética , Caramujos/anatomia & histologia , Animais , Pesos e Medidas Corporais , Análise Multivariada , Tailândia
9.
Lupus ; 18(7): 630-8, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19433464

RESUMO

Cigarette smoking may be associated with an increased risk of systemic lupus erythematosus (SLE), but the underlying mechanism of this association remains unclear. N-acetyltransferase 2 (NAT2) is highly variable and detoxifies aromatic amines, an important class of carcinogens in tobacco smoke. Individuals who possess homozygous polymorphic alleles have a slower rate of metabolic detoxification of aromatic amines. We investigated the relationship of the NAT2 polymorphism to the risk of SLE with special reference to the interaction with cigarette smoking among 152 SLE cases and 427 controls in a female Japanese population. NAT2 4, NAT2 5B, NAT2 6A and NAT2 7B alleles were detected with polymerase chain reaction-restriction fragment length polymorphism. Individuals carrying the 4/4 genotype are rapid acetylators, whereas those with homozygous non- 4 genotypes have a slow acetylator phenotype. Cigarette smoking was associated with an increased risk of SLE (odds ratio [OR] = 2.26; 95% confidence interval [CI] = 1.46-3.50). The slow acetylator genotype of NAT2 was significantly associated with an increased risk of SLE (OR = 2.34, 95% CI = 1.21-4.52) compared with the rapid acetylator genotype. A gene-environment interaction was suggested, with a combination of the NAT2 slow acetylator genotype and smoking conferring significantly higher risk (OR = 6.44, 95% CI = 3.07-13.52; attributable proportion due to interaction = 0.50, 95% CI = 0.12-0.88), compared with the NAT2 rapid acetylator genotype and no history of smoking. This study suggests that, in this Japanese population, the NAT2 slow acetylator status may be a determinant in susceptibility to SLE.


Assuntos
Arilamina N-Acetiltransferase/genética , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Polimorfismo Genético/genética , Fumar/efeitos adversos , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Japão , Lúpus Eritematoso Sistêmico/etnologia , Pessoa de Meia-Idade , Fatores de Risco
10.
J Evol Biol ; 20(2): 661-72, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17305832

RESUMO

Diverse animals exhibit left-right asymmetry in development. However, no example of dimorphism for the left-right polarity of development (whole-body enantiomorphy) is known to persist within natural populations. In snails, whole-body enantiomorphs have repeatedly evolved as separate species. Within populations, however, snails are not expected to exhibit enantiomorphy, because of selection against the less common morph resulting from mating disadvantage. Here we present a unique example of evolutionarily stable whole-body enantiomorphy in snails. Our molecular phylogeny of South-east Asian tree snails in the genus Amphidromus indicates that enantiomorphy has likely persisted as the ancestral state over a million generations. Enantiomorphs have continuously coexisted in every population surveyed spanning a period of 10 years. Our results indicate that whole-body enantiomorphy is maintained within populations opposing the rule of directional asymmetry in animals. This study implicates the need for explicit approaches to disclosure of a maintenance mechanism and conservation of the genus.


Assuntos
Evolução Biológica , Padronização Corporal/genética , Caramujos/anatomia & histologia , Animais , DNA Mitocondrial/química , Variação Genética , Filogenia , RNA Ribossômico 16S/química , RNA Ribossômico 16S/classificação , Seleção Genética , Alinhamento de Sequência , Análise de Sequência de DNA , Caramujos/classificação
11.
Acta Paediatr ; 93(1): 22-4, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14989434

RESUMO

UNLABELLED: Early observations emphasized the possible development of hyponatraemia in hypothyroid children and adults, but recently this has been questioned. AIM: To investigate whether hyponatraemia develops in hypothyroid status by examining sodium handling in screening-detected neonates and infants with congenital hypothyroidism (CH). METHODS: Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), sodium (Na), creatinine (Cr), urinary Na, Cr, fractional sodium excretion rate (FENa) and other chemicals were measured before and after L-thyroxine (LT4) replacement therapy in 32 screening-detected CH neonates (11M, 21F) and 16 age-matched control neonates. RESULTS: No cases of hyponatraemia were found in the 32 CH neonates. Their serum Na concentrations (139.1 +/- 1.5 mmol/L, ranging from 136 to 142 mmol/L, median 139 mmol/L) were not statistically different from those of 16 control neonates (139.3 +/- 1.3 mmol/L, ranging from 137 to 142 mmol/L, median 139 mmol/L). No correlation was found between serum levels of TSH and FT4 and serum Na or FENa. No significant changes were found in serum Na concentrations in hypothyroid neonates two months after LT4 replacement therapy. The serum Na concentration (139.1 +/- 0.3 mmol/L, n = 25) before treatment did not change statistically (138.9 +/- 0.2 mmol/L, n = 25) two months after LT4 replacement therapy. CONCLUSION: As seen in various earlier reports, hyponatraemia can occur in hypothyroid patients, but no causal relationship exists between them. When hyponatraemia is detected in hypothyroid children, it does not seem to be directly related to lack of thyroid hormones and therefore other possible causes should be sought.


Assuntos
Hipotireoidismo Congênito , Hiponatremia/etiologia , Sódio/sangue , Hormônios Tireóideos/sangue , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/complicações , Lactente , Recém-Nascido , Sódio/urina , Hormônios Tireóideos/uso terapêutico
12.
J Morphol ; 250(3): 225-35, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11746462

RESUMO

The structure of precursors to fungiform papillae without taste buds, prior to the arrival of sensory nerve fibers at the papillae, was examined in the fetal rat on embryonic day 13 (E13) and 16 (E16) by light and transmission electron microscopy in an attempt to clarify the mechanism of morphogenesis of these papillae. At E13, a row of rudiments of fungiform papillae was arranged along both sides of the median sulcus of the lingual dorsal surface, and each row consisted of about 10 rudiments. There was no apparent direct contact between papillae rudiments and sensory nerves at this time. Bilaterally towards the lateral side of the tongue, adjacent to these first rudiments of fungiform papillae, a series of cord-like invaginations of the dorsal epithelium of the tongue into the underlying connective tissue, representing additional papillary primordia parallel to the first row, was observed. The basal end of each invagination was enlarged as a round bulge, indented at its tip by a mound of fibroblasts protruding into the bulge. At E16 there was still no apparent direct contact between rudiments of fungiform papillae and sensory nerves. Each rudiment apically contained a spherical core of aggregating cells, which consisted of a dense assembly of large, oval cells unlike those in other areas of the lingual dorsal epithelium. The differentiation of these aggregated cells was unclear. The basal lamina was clearly recognizable between the epithelium of the rudiment of fungiform papillae and the underlying connective tissue. Spherical structures, which appeared to be sections of the cord-like invaginations of the lingual epithelium that appeared on E13, were observed within the connective tissue separated from the dorsal lingual epithelium. Transverse sections of such structures revealed four concentric layers of cells: a central core, an inner shell, an outer shell, and a layer of large cells. Bundles of fibers were arranged in the central core, and the diameters of bundles varied somewhat depending on the depth of the primordia within the connective tissue and their distance from the median sulcus. Ultrastructural features of cells in the outer shell differed significantly in rudiments close to the lingual epithelium as compared to those in deeper areas of connective tissue. Around the outer shell there was a large-cell layer consisting of one to three layers of radially elongated, oval cells that contained many variously sized, electron-dense, round granules. Large numbers of fibroblasts formed dense aggregates around each spherical rudiment, and were separated by the basal lamina from the large-cell epithelial layer. Progressing from deep-lying levels of the rudiments of the papillae to levels close to the lingual surface epithelium, the central core, inner shell, and outer shell gradually disappeared from the invaginated papillary cords.


Assuntos
Papilas Gustativas/embriologia , Papilas Gustativas/ultraestrutura , Animais , Desenvolvimento Embrionário e Fetal , Idade Gestacional , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley
13.
Nat Genet ; 29(4): 441-6, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11726931

RESUMO

Because plants depend on light for growth, their development and physiology must suit the particular light environment. Plants native to different environments show heritable, apparently adaptive, changes in their response to light. As a first step in unraveling the genetic and molecular basis of these naturally occurring differences, we have characterized intraspecific variation in a light-dependent developmental process-seedling emergence. We examined 141 Arabidopsis thaliana accessions for their response to four light conditions, two hormone conditions and darkness. There was significant variation in all conditions, confirming that Arabidopsis is a rich source of natural genetic diversity. Hierarchical clustering revealed that some accessions had response patterns similar to known photoreceptor mutants, suggesting changes in specific signaling pathways. We found that the unusual far-red response of the Lm-2 accession is due to a single amino-acid change in the phytochrome A (PHYA) protein. This change stabilizes the light-labile PHYA protein in light and causes a 100-fold shift in the threshold for far-red light sensitivity. Purified recombinant Lm-2 PHYA also shows subtle photochemical differences and has a reduced capacity for autophosphorylation. These biochemical changes contrast with previously characterized natural alleles in loci controlling plant development, which result in altered gene expression or loss of gene function.


Assuntos
Arabidopsis/efeitos da radiação , Luz , Arabidopsis/fisiologia , Plantas Geneticamente Modificadas
14.
Planta ; 213(5): 716-21, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11678275

RESUMO

Brassinazole is the only known specific brassinosteroid (BR)-biosynthesis inhibitor, and it has been shown to be useful for elucidating the function of BRs. In the course of a structure-activity relationship study of brassinazole, we found a more specific BR-biosynthesis inhibitor, Brz2001. This new inhibitor induced similar morphological changes to those seen in brassinazole-treated plants, including Arabidopsis thaliana (L.) Heynh., Nicotiana tabacum L., and Lepidium sativum L. These changes included dwarfism with altered leaf morphology, including downward curling and dark-green color, and the changes were reversed by brassinolide. Although the structure of Brz2001 is similar to that of uniconazole, a gibberellin-biosynthesis inhibitor, Brz2001-treated plants showed almost no recovery with the addition of gibberellic acid (GA3). Comparison of the responses of both brassinazole- and Brz2001-treated cress to brassinolide and GA3 suggested that Brz2001 is a more specific BR-biosynthesis inhibitor than brassinazole. Unlike the results just described, Brz2001-treated rice did not show any morphological changes. This suggests that the roles of BRs in rice may be different from those in the dicotyledonous plants examined in this study. Brz2001 can be used to clarify the function of BRs in dicots as a complement to BR-deficient mutants, and to elucidate the different roles of BRs in monocots and dicots.


Assuntos
Fitosteróis/antagonistas & inibidores , Reguladores de Crescimento de Plantas/farmacologia , Triazóis/farmacologia , Arabidopsis/metabolismo , Brassinosteroides , Colestanóis/farmacologia , Cotilédone/efeitos dos fármacos , Cotilédone/crescimento & desenvolvimento , Giberelinas/farmacologia , Hipocótilo/efeitos dos fármacos , Hipocótilo/crescimento & desenvolvimento , Oryza/metabolismo , Fitosteróis/biossíntese , Desenvolvimento Vegetal , Reguladores de Crescimento de Plantas/química , Plantas/efeitos dos fármacos , Plantas/metabolismo , Esteroides Heterocíclicos/farmacologia , Relação Estrutura-Atividade , Tabaco/metabolismo , Triazóis/química
15.
Plant Cell Physiol ; 42(9): 1006-11, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11577196

RESUMO

Brassinazole (Brz) is a specific brassinosteroid biosynthesis inhibitor. Cress plants (Lepidium sativum) grown in medium containing Brz exhibited a slight predominance of phloem differentiation at the expense of xylem differentiation and remarkable inhibition of the development of secondary xylem. This result indicates that brassinosteroids function in xylem development in vivo.


Assuntos
Brassicaceae/fisiologia , Fitosteróis/biossíntese , Reguladores de Crescimento de Plantas/metabolismo , Triazóis/farmacologia , Arabidopsis/metabolismo , Transporte Biológico , Brassicaceae/crescimento & desenvolvimento , Brassinosteroides , Diferenciação Celular , Divisão Celular , Colestanóis/metabolismo , Fitosteróis/antagonistas & inibidores , Caules de Planta/citologia , Caules de Planta/crescimento & desenvolvimento , Esteroides Heterocíclicos/metabolismo
16.
Thyroid ; 11(8): 765-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11525269

RESUMO

Hypothyroid status is believed to cause various metabolic changes in infants. However, it is interesting that even severely hypothyroid neonates, detected during mass neonatal screening, rarely show bradycardia, hypothermia, or inactivity. To study cardiac functions of screen-detected neonates with congenital hypothyroidism (CH), we recorded the electrocardiograms (ECG) of 53 screen-detected CH neonates before levothyroxine (LT4) replacement therapy, and 15 age-matched normal neonates for controls. The 53 CH neonates were divided into two groups according to initial serum thyroid hormone levels: a mildly hypothyroid group (n = 37), serum thyroid-stimulating hormone (TSH) less than 100 microIU/mL and free thyroxine (FT4) 0.6 ng/dl or more; and a severely hypothyroid group (n = 16), TSH 100 microIU/mL or more and FT4 less than 0.6 ng/dL. TSH, FT4, and other blood chemicals were measured on an autoanalyzer (Hitachi 7170). After blood sampling, the ECG was recorded during induced sleep by oral administration of triclofos sodium syrup. ECG parameters, including HR, PR, QRS, QT time and corrected QT time (QTc) were automatically obtained, using an auto-ECG analyzing system. The following results were obtained. No CH patients showed abnormal ECG findings. There was no significant difference of the mean heart rates (HRs) between the mildly hypothyroid (147.5 +/- 16.3 beats per minute) and the control group (148.3 +/- 12.1 beats per minute). The mean HR in the severely hypothyroid group (134.0 +/- 17.9 beats per minute, p = 0.007) was significantly low compared with the normal control group. However, all values were within normal ranges. QTc in the severely hypothyroid group (0.414 +/- 0.015, p = 0.033) was significantly shorter than in the control group (0.440 +/- 0.052). No statistical differences of PR, QRS, and QT time were noted among the three groups. All ECG parameters were within normal ranges. HR positively correlated with FT4 and log (FT4), and negatively with TSH and log (TSH). From these results we conclude that the deficiency of thyroid hormones does not affect ECG findings of congenitally hypothyroid neonates. This may be consistent with the unexpectedly mild signs and symptoms of screen-detected hypothyroid neonates.


Assuntos
Hipotireoidismo Congênito , Eletrocardiografia , Hipotireoidismo/fisiopatologia , Tireotropina/deficiência , Tiroxina/deficiência , Frequência Cardíaca , Humanos , Recém-Nascido , Valores de Referência , Tireotropina/sangue , Tiroxina/sangue
17.
Biochem Biophys Res Commun ; 285(1): 98-104, 2001 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-11437378

RESUMO

Obtusifoliol 14alpha-demethylase is a plant orthologue of sterol 14alpha-demethylase (CYP51) essential in sterol biosynthesis. We have prepared CYP51 antisense Arabidopsis in order to shed light on the sterol and steroid hormone biosynthesis in plants. Arabidopsis putative CYP51 cDNA (AtCYP51) was obtained from Arabidopsis expressed sequence tag (EST) library and its function was examined in a yeast lanosterol 14alpha-demethylase (Erg11) deficient mutant. A recombinant AtCYP51 protein fused with a yeast Erg11 signal-anchor peptide was able to complement the erg11 mutation, which confirmed AtCYP51 to be a functional sterol 14alpha-demethylase. AtCYP51 was then used to generate transgenic Arabidopsis by transforming with pBI vector harboring AtCYP51 in the antisense direction under CaMV35S promoter. The resulting transgenic plants were decreased in accumulation of AtCYP51 mRNA and increased in the amount of endogenous obtusifoliol. They showed a semidwarf phenotype in the early growth stage and a longer life span than control plants. This newly found phenotype is different from previously characterized brassinosteroid (BR)-deficient campesterol biosynthesis mutants.


Assuntos
Arabidopsis/genética , Sistema Enzimático do Citocromo P-450/genética , Oxirredutases/genética , Sequência de Aminoácidos , Arabidopsis/enzimologia , Arabidopsis/crescimento & desenvolvimento , Sequência de Bases , Clonagem Molecular , Primers do DNA , Etiquetas de Sequências Expressas , Dados de Sequência Molecular , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Proteínas Recombinantes/genética , Esterol 14-Desmetilase
18.
Biosci Biotechnol Biochem ; 65(6): 1275-83, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11471724

RESUMO

The cell growth and plastid development of cultured green tobacco cells were maintained by the phytohormone cytokinin. After subculture into cytokinin-free medium, when cytokinin treatment was resumed, physiological changes induced by cytokinin were analyzed. Changes in chlorophyll biosynthesis and photosynthetic gene expression were observed 1 week after cytokinin induction, and changes in cell growth were observed 2 weeks after cytokinin induction. Two cytokinin-induced genes (cig) were isolated from these cells using the fluorescent differential display technique. Northern analysis confirmed that expression of these cig was induced by both natural and synthetic cytokinins. The expression of cig1 was also induced by abscisic acid, and its cDNA sequence was similar to the proline dehydrogenase gene. The expression of cig2 is specific to cytokinin and is not induced by other phytohormones. The amino acid sequence encoded by cig2 is similar to the GDP/GTP exchange factor eIF2B, which regulates translation initiation. The expression of these cig suggests a complex induction system involving cytokinin and other phytohormones.


Assuntos
Citocininas/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Tabaco/genética , Sequência de Aminoácidos , Northern Blotting , Células Cultivadas , Clorofila/metabolismo , Clonagem Molecular , Fluorescência , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Dados de Sequência Molecular , Reguladores de Crescimento de Plantas/metabolismo , Prolina Oxidase/metabolismo , Tabaco/citologia , Tabaco/metabolismo
19.
Biosci Biotechnol Biochem ; 65(4): 817-22, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11388458

RESUMO

A series of 5-substituted pyrimidine derivatives was synthesized, and their ability to inhibit brassinosteroid biosynthesis was tested. The biological activity of these compounds was evaluated by the cress stem elongation method. Among the synthesized compounds, alpha-(4-chlorophenyl)-alpha-phenyl-5-pyrimidinemethanol (DPPM 4) exhibited potent inhibitory activity for retarding cress stem elongation in the light. This inhibition was reversed by the application of 10 nM brassinolide, but not by 1 microM GA3. DPPM 4 also affected Arabidopsis growth in the dark. DPPM 4-treated Arabidopsis had phenotypes like those of brassinosteroid-deficient mutants, with short hypocotyls and open cotyledons, in the dark. These biological changes were restored by the co-application of 10 nM brassinolide, but not by 1 microM GA3, suggesting that the primary site of action of DPPM 4 was the brassinosteroid biosynthetic pathway.


Assuntos
Plantas/metabolismo , Pirimidinas/síntese química , Pirimidinas/farmacologia , Esteroides/biossíntese , Fenótipo , Plantas/efeitos dos fármacos , Plantas/genética , Sementes/química
20.
J Biol Chem ; 276(28): 25687-91, 2001 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-11319239

RESUMO

Brassinazole, a synthetic chemical developed in our laboratory, is a triazole-type brassinosteroid biosynthesis inhibitor that induces dwarfism in various plant species. The target sites of brassinazole were investigated by chemical analyses of endogenous brassinosteroids (BRs) in brassinazole-treated Catharanthus roseus cells. The levels of castasterone and brassinolide in brassinazole-treated plant cells were less than 6% of the levels in untreated cells. In contrast, campestanol and 6-oxocampestanol levels were increased, and levels of BR intermediates with hydroxy groups on the side chains were reduced, suggesting that brassinazole treatment reduced BR levels by inhibiting the hydroxylation of the C-22 position. DWF4, which is an Arabidopsis thaliana cytochrome P450 isolated as a putative steroid 22-hydroxylase, was expressed in Escherichia coli, and the binding affinity of brassinazole and its derivatives to the recombinant DWF4 were analyzed. Among several triazole derivatives, brassinazole had both the highest binding affinity to DWF4 and the highest growth inhibitory activity. The binding affinity and the activity for inhibiting hypocotyl growth were well correlated among the derivatives. In brassinazole-treated A. thaliana, the CPD gene involved in BR biosynthesis was induced within 3 h, most likely because of feedback activation caused by the reduced levels of active BRs. These results indicate that brassinazole inhibits the hydroxylation of the C-22 position of the side chain in BRs by direct binding to DWF4 and that DWF4 catalyzes this hydroxylation reaction.


Assuntos
Proteínas de Arabidopsis , Sistema Enzimático do Citocromo P-450/metabolismo , Plantas/metabolismo , Triazóis/metabolismo , Hidroxilação , Triazóis/química
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