RESUMO
Take-all dynamics within crops differing in cropping history (the number of previous consecutive wheat crops) were analyzed using an epidemiological model to determine the processes affected during take-all decline. The model includes terms for primary infection, secondary infection, inoculum decay, and root growth. The average rates of root production did not vary with cropping history. The force of primary infection increased from a low level in 1st wheat crops, to a maximum in 2nd to 4th wheat crops, and then to intermediate levels thereafter. The force of secondary infection was low but increased steadily during the season in first wheat crops, was delayed but rose and fell sharply in 2nd to 4th wheat crops, and for 5th and 7th wheat crops returned to similar dynamics as that for 1st wheat crops. Chemical seed treatment with silthiofam had no consistent effect on the take-all decline process. We conjecture that these results are consistent with (i) low levels of particulate inoculum prior to the first wheat crop leading to low levels of primary infection, low levels of secondary infection, and little disease suppression; (ii) net amplification of inoculum during the first wheat crop and intercrop period; (iii) increased levels of primary and secondary infection in subsequent crops, but higher levels of disease suppression; and (iv) an equilibrium between the pathogen and antagonist populations by the 5th wheat, reflected by lower overall rates of primary infection, secondary infection, disease suppression and hence, disease severity.
Assuntos
Doenças das Plantas/estatística & dados numéricos , Estações do Ano , Triticum/microbiologia , Intervalos de Confiança , Produtos Agrícolas/microbiologia , Métodos Epidemiológicos , Doenças das Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Fatores de TempoRESUMO
ABSTRACT Epidemiological modeling is used to examine the effect of silthiofam seed treatment on field epidemics of take-all in winter wheat. A simple compartmental model, including terms for primary infection, secondary infection, root production, and decay of inoculum, was fitted to data describing change in the number of diseased and susceptible roots per plant over thermal time obtained from replicated field trials. This produced a composite curve describing change in the proportion of diseased roots over time that increased monotonically to an initial plateau and then increased exponentially thereafter. The shape of this curve was consistent with consecutive phases of primary and secondary infection. The seed treatment reduced the proportion of diseased roots throughout both phases of the epidemic. However, analysis with the model detected a significant reduction in the rate of primary, but not secondary, infection. The potential for silthiofam to affect secondary infection from diseased seminal or adventitious roots was examined in further detail by extending the compartmental model and fitting to change in the number of diseased and susceptible seminal or adventitious roots. Rates of secondary infection from either source of infected roots were not affected. Seed treatment controlled primary infection of seminal roots from particulate inoculum but not secondary infection from either seminal or adventitious roots. The reduction in disease for silthiofam-treated plants observed following the secondary infection phase of the epidemic was not due to long-term activity of the chemical but to the manifestation of disease control early in the epidemic.
RESUMO
The concept and application of ethical principles in the context of medical research is changing rapidly. This is especially true for fast moving fields such as gene therapy, a relatively new but rapidly maturing field offering opportunities to influence health at a fundamental level, which may become a cornerstone of medicine. By 2004, over 700 gene therapy clinical protocols had been initiated worldwide, and two highly publicized gene therapy-related side effects have helped to shape recent ethical debate. These events have influenced not only clinical trial design but also public opinion and systems of independent oversight. Both the science of gene therapy and the regulatory environment are continually evolving. How well the field is able to respond to these challenges will determine the extent to which gene therapy will ultimately be integrated into medical practice.
Assuntos
Terapia Genética/tendências , Animais , Medicina Clínica/tendências , Ética Médica , Previsões , Terapia Genética/ética , Humanos , Projetos de Pesquisa , SegurançaRESUMO
Consumers have varying expectations and knowledge about evidence-based medicine (EBM), but expect the healthcare system to offer best practice based on the latest evidence. With the increasing power of the consumer movement, EBM has the potential to promote informed participation in health decision making by individual consumers and carers. To more effectively incorporate consumer experiences, views and concerns into the evidence base, there needs to be greater value put on qualitative research and acknowledgement of its importance. Consumers would like the research agenda to reflect population health needs, and for there to be more consultation about evidence-based decisions on access to care and rationing, and greater understanding of consumers' attitudes in decisions about treatment. Consumers want patient-centred healthcare and therefore must be involved collaboratively in the way EBM is used by health services and health practitioners.
Assuntos
Participação da Comunidade , Medicina Baseada em Evidências , Acessibilidade aos Serviços de Saúde , Austrália , HumanosRESUMO
BACKGROUND: Consumer health information is a necessary component of patient care and consumer participation. OBJECTIVE: To outline the findings of the 'Assessing the Quality of Consumer Health Information Project' and discuss strategies for improving consumer information. DISCUSSION: The pamphlets identified in this study were not developed with consumer input with consequent deficits apparent. Providers and consumers appeared to use the information for very different purposes but both groups were critical of the ambiguous terminology and lack of quantified data. The provision of relevant information is a fundamental prerequisite of consumer participation in decision making in health care. Such information needs to be available, accurate, and understandable.
Assuntos
Serviços de Informação/normas , Folhetos , Educação de Pacientes como Assunto/normas , Garantia da Qualidade dos Cuidados de Saúde , Austrália , Comportamento de Escolha , Participação da Comunidade/estatística & dados numéricos , Medicina Baseada em Evidências , Humanos , Satisfação do Paciente , Preconceito , Resultado do TratamentoRESUMO
Muscarinic agonists alter the metabolism of amyloid precursor protein, leading to an increase in alpha-secretase cleavage and a decreased production of amyloidogenic peptides; suggesting that these compounds might modify the Alzheimer's disease process. A second therapeutic target in AD is the accumulation of stably phosphorylated tau into neurofibrillary tangles; an early event correlating with cognitive impairment. Glycogen synthase kinase-3 (GSK-3beta) phosphorylates tau and is inhibited via protein kinase C (PKC). As certain muscarinic receptors are linked to PKC, we examined the effect of a range of agonists on GSK-3beta phosphorylation of tau. In neurons a nonspecific muscarinic agonist, carbachol, reduced tau phosphorylation. In nonneuronal cells expressing the ml receptor a range of ml agonists reduced transiently-expressed tau phosphorylation and altered its microtubulebinding properties. These findings link the two pathological process of AD-APP metabolism and tau phosphorylation - and suggest that muscarinic and other cholinergic compounds might have disease-modifying properties.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Proteínas Quinases Dependentes de Cálcio-Calmodulina/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Agonistas Muscarínicos/farmacologia , Neurônios/efeitos dos fármacos , Receptores Muscarínicos/efeitos dos fármacos , Proteínas tau/efeitos dos fármacos , Acetilcolina/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/efeitos dos fármacos , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/fisiologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Carbacol/farmacologia , Células Cultivadas/citologia , Células Cultivadas/metabolismo , Feto , Quinase 3 da Glicogênio Sintase , Quinases da Glicogênio Sintase , Cloreto de Lítio/farmacologia , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/metabolismo , Tetrazóis/farmacologia , Tiadiazóis/farmacologia , Proteínas tau/metabolismoRESUMO
A total of 161 fungal isolates were obtained from the surface-sterilized roots of field-grown oat and wheat plants in order to investigate the nature of the root-colonizing fungi supported by these two cereals. Fungi were initially grouped according to their colony morphologies and then were further characterized by ribosomal DNA sequence analysis. The collection contained a wide range of ascomycetes and also some basidiomycete fungi. The fungi were subsequently assessed for their abilities to tolerate and degrade the antifungal oat root saponin, avenacin A-1. Nearly all the fungi obtained from oat roots were avenacin A-1 resistant, while both avenacin-sensitive and avenacin-resistant fungi were isolated from the roots of the non-saponin-producing cereal, wheat. The majority of the avenacin-resistant fungi were able to degrade avenacin A-1. These experiments suggest that avenacin A-1 is likely to influence the development of fungal communities within (and possibly also around) oat roots.
Assuntos
Grão Comestível/microbiologia , Fungos/isolamento & purificação , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Avena/microbiologia , Sequência de Bases , Primers do DNA/genética , DNA Fúngico/genética , DNA Ribossômico/genética , Resistência Microbiana a Medicamentos , Fungos/efeitos dos fármacos , Fungos/genética , Filogenia , Doenças das Plantas/microbiologia , Raízes de Plantas/microbiologia , Saponinas/metabolismo , Saponinas/farmacologia , Triticum/microbiologia , VirulênciaRESUMO
A consumer survey was designed to assess the quality of mental health and substance abuse services and evaluate insurance plans that provide such services. This paper describes the development of the Consumer Assessment of Behavioral Health Services instrument, which began with a review of existing consumer satisfaction surveys and input from several groups working toward development of nationally standardized satisfaction instruments. Consumer focus groups were used to ensure that all the important domains of quality were included, and group members were interviewed to ensure that all items on the instrument were understandable. Results of a pilot test conducted with 160 consumers, 82 enrolled in Medicaid plans and 78 in commercial plans, suggested that the survey was able to distinguish between the two groups in terms of evaluations of their care and insurance plans. Future efforts will focus on further testing of larger, more diverse samples and on developing scoring and reporting formats for the survey that will be useful to consumers and purchasers in choosing behavioral health services and plans.
Assuntos
Comportamento do Consumidor , Pesquisas sobre Atenção à Saúde , Sistemas Pré-Pagos de Saúde/normas , Serviços de Saúde Mental/normas , Transtornos Relacionados ao Uso de Substâncias/terapia , Inquéritos e Questionários , Sistemas Pré-Pagos de Saúde/economia , Humanos , Seguro Psiquiátrico , Medicaid , Serviços de Saúde Mental/estatística & dados numéricos , Serviços de Saúde Mental/provisão & distribuição , Projetos Piloto , Estudos Retrospectivos , Estados UnidosRESUMO
NO is an important mediator in sepsis. It has been unequivocally established that it is the major determinant in the vasodilatation and consequent hypotension in experimental animals following the administration of LPS. It is cytotoxic, particularly in combination with superoxide anions, and exerts negative inotropic and chronotropic effects on the heart. The exact role that these functions play in sepsis, however, remain unclear. Similarly, its immunomodulatory and cerebral effects, although potentially important, remain of uncertain significance in sepsis. Regulation of such a pivotal molecule is clearly extremely important: the data described here show that not only is this regulation extremely complex, but it appears to vary in different cell types. The implication of this finding for future clinical work is clear. NO production is not all bad: in some circumstances, it may be desirable to differentially regulate iNOS activity such that production is restricted in some cell types but not in others. The work described here begins to offer the possibility of identifying new molecular targets which allow this kind of differential regulation.
Assuntos
Citocinas/fisiologia , Músculo Liso Vascular/enzimologia , Óxido Nítrico Sintase/biossíntese , Animais , Regulação para Baixo , Ativação Enzimática , Indução Enzimática , Regulação Enzimológica da Expressão Gênica , Humanos , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo IIRESUMO
Nitric oxide production in a variety of inflammatory conditions is dependent on the synthesis of the enzyme, inducible nitric-oxide synthase (iNOS). The gene for this enzyme is regulated by a number of inflammatory cytokines, including interferon-gamma. Transcriptional activation of the gene is dependent on the interferon-gamma-induced transcription factor, interferon regulatory factor-1 (IRF-1). Using a 99-base pair segment of the iNOS gene promoter encompassing nucleotides -979 to -881, a region essential for gene activation by cytokines, we show that with increasing concentrations of added IRF-1, a monomeric then a dimeric complex form. Molecular footprinting analysis shows that the factor binds initially to a canonical IRF-1 site as a monomer. The region of binding is then extended both in a 5' and 3' direction on formation of the dimeric complex, with additional contacts in the minor groove of DNA. Binding of the second molecule of IRF-1 is dependent on the presence of the initial bound protein. Sequential binding of IRF-1 to form a dimeric complex has not been described previously, and we show that formation of this dimeric complex is essential for full activation of the iNOS gene by cytokines in vascular smooth muscle cells.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Óxido Nítrico Sintase/genética , Fosfoproteínas/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular , Simulação por Computador , Pegada de DNA , Fator Regulador 1 de Interferon , Mutagênese Sítio-Dirigida , Óxido Nítrico Sintase/metabolismo , Ligação Proteica , RatosRESUMO
This review focuses on two important routes of gene activation mediated by proinflammatory cytokines, which serve as a paradigm for mechanisms of specificity and synergy in cytokine regulated gene activity: STAT (signal transducers and activators of transcription)-related gene activation and the pathways initiated by proinflammatory cytokines leading to the activation of the NF-kappa B family of transcriptional activators. The proinflammatory cytokine cascade is involved in both the normal immune response and in the pathogenesis of several disease states. An understanding of specificity and synergism in these pathways offers an opportunity to develop novel therapeutic drugs for the selective manipulation of these disease processes. Such potential targets are examined in this review.
Assuntos
Citocinas/fisiologia , Regulação da Expressão Gênica , Transdução de Sinais , Animais , Citocinas/farmacologia , Sinergismo Farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Ativação TranscricionalRESUMO
The production of inducible nitric oxide synthase (iNOS) within vascular smooth muscle (VSM) cells following exposure to proinflammatory cytokines is a major cause of the vasorelaxation and hypotension of septic shock. We have defined the cytokine-responsive element of the murine iNOS promoter, transfected into a VSM cell line, and the role of the NF-kappa B/Rel family of proteins in iNOS gene activation in these cells. The combination of interleukin-1, interferon-gamma, and tumor necrosis factor-alpha stimulates promoter activity by a factor of 8.1-fold; single cytokines show little activity, while pairs of cytokines produce an intermediate effect. Using a series of promoter deletion mutants, we have defined the cytokine-responsive element from position -890 to -1002; this region contains an NF-kappa B-binding site as well as a number of interferon response elements. Nuclear proteins from cytokine-stimulated VSM cells which bind to an oligonucleotide containing this kappa B site are composed of p65 together with an unidentified protein of 50 kDa, which is not a known Rel family member. A promoter mutant with a 2-base pair change within this kappa B site, which abolishes NF-kappa B binding, has an activity of only approximately 34% (S.E. +/- 1.5) of the wild-type promoter. In addition, protein binding to this site is abolished by a specific inhibitor of NF-kappa B activation, which also abrogates iNOS activity. Residual inducibility in such mutant promoters is attributable to the presence of an independently functioning downstream kappa B site (-85 to -75). The mechanism by which NF-kappa B activates the iNOS promoter in VSM cells in response to cytokines appears to be markedly different to that operative in macrophages in response to lipopolysaccharide.
Assuntos
Citocinas/farmacologia , Músculo Liso Vascular/enzimologia , NF-kappa B/fisiologia , Óxido Nítrico Sintase/genética , Regiões Promotoras Genéticas , Animais , Sequência de Bases , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , Dados de Sequência Molecular , Prolina/análogos & derivados , Prolina/farmacologia , Ratos , Tiocarbamatos/farmacologia , TransfecçãoRESUMO
The regulation of the spvR promoter from the Salmonella dublin virulence plasmid was monitored using promoter-reporter gene fusion constructs. Activity was dependent upon the presence of the spv region and was affected by the number of copies of the spv region present within the cell. Activity remained constant throughout exponential growth, and increased rapidly with the onset of stationary phase, under both aerobic and anaerobic conditions. Additionally, the level of spvR expression was controlled by the availability of iron, activity being greatest under low iron conditions in stationary phase. The spvA gene product negatively regulated spvR expression in a dose-dependent manner, indicating that SpvA provides a negative feedback mechanism for this operon.
Assuntos
Regulação Bacteriana da Expressão Gênica , Genes Reguladores , Plasmídeos/genética , Salmonella/genética , Salmonella/patogenicidade , Animais , Sequência de Bases , Genes Bacterianos , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Mapeamento por Restrição , Infecções por Salmonella/microbiologia , Virulência/genéticaRESUMO
A non-invasive exercise method was used to look for myocardial damage in apparently normal children who had received moderate doses of anthracyclines for treatment of cancer. 19 children (mean [SD] age 10.6 [4.3] years) who had received anthracyclines (mean total dose 230 [119] mg/m2) and 10 who had received other cytotoxic drugs (mean age 13.3 [4.9] years) were selected from 263 children attending routine follow-up examinations. They underwent measurement of heart rate, blood pressure, and left ventricular dimensions by echocardiography before and after exercise on a bicycle for a maximum of 10 min. All 29 were in remission. All the subjects showed normal fractional shortening (FS = left ventricular end-diastolic minus end-systolic diameter as a percentage of the end-diastolic diameter) at rest, but the increase in FS on exercise was significantly lower in the children who had received anthracyclines than in those who had not (3 [16]% vs 23 [17]%; p less than 0.05). This difference remained significant after adjustment for age and drug exposure. However, there were no significant differences between the groups in the adjusted mean percentage changes on exercise in heart rate or systolic or diastolic blood pressure. Disease type had no effect on the cardiological indices. Thus, many children who have received anthracyclines may have suffered subclinical myocardial damage. Post-exercise echocardiography seems a useful non-invasive method for detecting such damage. Long-term cardiological follow-up of these patients is needed.
Assuntos
Daunorrubicina/efeitos adversos , Contração Miocárdica/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Função Ventricular/efeitos dos fármacos , Adolescente , Pressão Sanguínea/efeitos dos fármacos , Criança , Pré-Escolar , Daunorrubicina/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Teste de Esforço , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Neoplasias/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologiaRESUMO
Selenium (Se) deficiency is associated with cardiac and skeletal muscle dysfunction. Twenty well children aged 2-16 years (10 male) attending the Phenylketonuria (PKU) Clinic at the Royal Children's Hospital, Brisbane, had low Se levels (mean 0.29 +/- 0.02 s.e.m. mumol/L; normal range 0.56-1.16 mumol/L). Their myocardial function was assessed at rest and after exercise provocation by M-mode echocardiography in order to exclude occult left ventricular dysfunction. At rest, fractional shortening (FS) was normal (mean 38.1 +/- 1.1 s.e.m. %, n = 20). After exercise, FS increased significantly (P less than 0.001) from 37.6 +/- 1.4% to 44.3 +/- 1.2%, n = 12). This was associated with a significant rise (P less than 0.001) in heart rate (HR) from 77.3 +/- 3.1 beats/min to 125.8 +/- 5.2 beats/min (n = 12). The normal resting FS and normal increase in FS and HR with exercise is evidence against significant cardiac impairment in this group of Se-deficient children.