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1.
Weed Res ; 58(4): 239-243, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30174354

RESUMO

Should the declining diversity of weed communities in conventionally managed arable fields be regarded as a problem? The answer to this question has tended to divide researchers into those whose primary focus is on conserving farmland biodiversity and those whose goals are dictated by weed control and maximising yield. Here, we argue that, regardless of how weeds are perceived, there are common ecological principles that should underpin any approach to managing weed communities, and, based on these principles, increasing in-field weed diversity could be advantageous agronomically as well as environmentally. We hypothesise that a more diverse weed community will be less competitive, less prone to dominance by highly adapted, herbicide-resistant species and that the diversity of the weed seedbank will be indicative of the overall sustainability of the cropping system. Common to these hypotheses is the idea that the intensification of agriculture has been accompanied by a homogenisation of cropping systems and landscapes, accounting for both declines in weed diversity and the reduced resilience of cropping systems (including the build-up of herbicide resistance). As such, weed communities represent a useful indicator of the success of rediversifying systems at multiple scales, which will be a central component of making agriculture and weed control more sustainable.

2.
Weed Res ; 58(4): 250-258, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30069065

RESUMO

Weedy plants pose a major threat to food security, biodiversity, ecosystem services and consequently to human health and wellbeing. However, many currently used weed management approaches are increasingly unsustainable. To address this knowledge and practice gap, in June 2014, 35 weed and invasion ecologists, weed scientists, evolutionary biologists and social scientists convened a workshop to explore current and future perspectives and approaches in weed ecology and management. A horizon scanning exercise ranked a list of 124 pre-submitted questions to identify a priority list of 30 questions. These questions are discussed under seven themed headings that represent areas for renewed and emerging focus for the disciplines of weed research and practice. The themed areas considered the need for transdisciplinarity, increased adoption of integrated weed management and agroecological approaches, better understanding of weed evolution, climate change, weed invasiveness and finally, disciplinary challenges for weed science. Almost all the challenges identified rested on the need for continued efforts to diversify and integrate agroecological, socio-economic and technological approaches in weed management. These challenges are not newly conceived, though their continued prominence as research priorities highlights an ongoing intransigence that must be addressed through a more system-oriented and transdisciplinary research agenda that seeks an embedded integration of public and private research approaches. This horizon scanning exercise thus set out the building blocks needed for future weed management research and practice; however, the challenge ahead is to identify effective ways in which sufficient research and implementation efforts can be directed towards these needs.

3.
Weed Res ; 57(5): 323-332, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28989202

RESUMO

Glyphosate use in the United Kingdom has more than doubled in the last 20 years. Much of this increase is driven by efforts to control herbicide resistant weeds, particularly Alopecurus myosuroides, prior to crop drilling. There is precedent for evolution of glyphosate resistance in similar situations, raising concerns over the sustainability of glyphosate use in the UK. We used dose-response experiments to examine variation in glyphosate sensitivity amongst 40 field-collected A. myosuroides populations. No populations were resistant to glyphosate, but ED 90 values ranged between 354 and 610 g a.i. ha-1. Five populations had ED 90 values significantly higher than the unexposed control population collected from a site at Rothamsted Research with no previous glyphosate exposure. Recurrent selection experiments were performed to determine whether variation in glyphosate sensitivity had a heritable basis. Following two rounds of selection, five of six field populations evolved significantly reduced sensitivity to glyphosate, with R/S ratios, based on estimated ED 50 values, ranging from 1.2 to 1.5. These results confirm that there is a heritable basis to variation in glyphosate sensitivity. The response to selection was modest. Evolved populations were not highly resistant to glyphosate, although some twice-selected individuals survived recommended field rates. These results do not represent definitive proof of the potential of A. myosuroides to evolve glyphosate resistance, although they do indicate caution is needed when considering the sustainability of increased glyphosate use to control this herbicide resistance-prone species.

4.
J Evol Biol ; 25(10): 1955-1964, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22913345

RESUMO

Pleiotropic fitness trade-offs will be key determinants of the evolutionary dynamics of selection for pesticide resistance. However, for herbicide resistance, empirical support for a fitness cost of resistance is mixed, and it is therefore also questionable what further ecological trade-offs can be assumed to apply to herbicide resistance. Here, we test the existence of trade-offs by experimentally evolving herbicide resistance in Chlamydomonas reinhardtii. Although fitness costs are detected for all herbicides, we find that, counterintuitively, the most resistant populations also have the lowest fitness costs as measured by growth rate in the ancestral environment. Furthermore, after controlling for differences in the evolutionary dynamics of resistance to different herbicides, we also detect significant positive correlations between resistance, fitness in the ancestral environment and cross-resistance to other herbicides. We attribute this to the highest levels of nontarget-site resistance being achieved by fixing mutations that more broadly affect cellular physiology, which results in both more cross-resistance and less overall antagonistic pleiotropy on maximum growth rate. Consequently, the lack of classical ecological trade-offs could present a major challenge for herbicide resistance management.


Assuntos
Chlamydomonas reinhardtii/efeitos dos fármacos , Chlamydomonas reinhardtii/genética , Aptidão Genética , Resistência a Herbicidas/genética , Herbicidas/toxicidade , Adaptação Fisiológica/genética , Animais , Relação Dose-Resposta a Droga , Herbicidas/administração & dosagem , Testes de Sensibilidade Microbiana , Modelos Biológicos
5.
Heredity (Edinb) ; 107(5): 386-94, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21540885

RESUMO

Plants exhibit a number of adaptive defence traits that endow resistance to past and current abiotic and biotic stresses. It is generally accepted that these adaptations will incur a cost when plants are not challenged by the stress to which they have become adapted--the so-called 'cost of adaptation'. The need to minimise or account for allelic variation at other fitness-related loci (genetic background control) is frequently overlooked when assessing resistance costs associated with plant defence traits. We provide a synthesis of the various experimental protocols that accomplish this essential requirement. We also differentiate those methods that enable the identification of the trait-specific or mechanistic basis of costs (direct methods) from those that provide an estimate of the impact of costs by examining the evolutionary trajectories of resistance allele frequencies at the population level (indirect methods). The advantages and disadvantages for each proposed experimental design are discussed. We conclude that plant resistance systems provide an ideal model to address fundamental questions about the cost of adaptation to stress. We also propose some ways to expand the scope of future studies for further fundamental and applied insight into the significance of adaptation costs.


Assuntos
Resistência à Doença/genética , Aptidão Genética , Plantas/genética , Adaptação Biológica/genética , Evolução Molecular , Frequência do Gene , Genes de Plantas , Genótipo , Modelos Genéticos , Seleção Genética
6.
Heredity (Edinb) ; 95(6): 485-92, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16175194

RESUMO

The frequency of phenotypic resistance to herbicides in previously untreated weed populations and the herbicide dose applied to these populations are key determinants of the dynamics of selection for resistance. In total, 31 Lolium rigidum populations were collected from sites with no previous history of exposure to herbicides and where there was little probability of gene flow from adjacent resistant populations. The mean survival frequency across all 31 populations following two applications of commercial rates (375 g ha(-1)) of the acetyl-coenzyme A carboxylase (ACCase) inhibiting herbicide, diclofop-methyl was 0.43%. Survivors from five of these populations were grown to maturity and seed was collected. Dose-response experiments compared population level resistance to diclofop-methyl in these selected lines with their original parent populations. A single cycle of herbicide selection significantly increased resistance in all populations (LD(50) R:S ratios ranged from 2.8 to 23.2), confirming the inheritance and genetic basis of phenotypic resistance. In vitro assays of ACCase inhibition by diclofop acid indicated that resistance was due to a non-target-site mechanism. Following selection with diclofop-methyl, the five L. rigidum populations exhibited diverse patterns of cross-resistance to ACCase and ALS-inhibiting herbicides, suggesting that different genes or gene combinations were responsible for resistance. The relevance of these results to the management of herbicide resistance are discussed.


Assuntos
Evolução Biológica , Resistência a Medicamentos/genética , Herbicidas/farmacologia , Lolium/genética , Éteres Fenílicos/farmacologia , Relação Dose-Resposta a Droga , Éteres Difenil Halogenados , Lolium/efeitos dos fármacos , Lolium/fisiologia , Fenótipo
7.
New Phytol ; 167(3): 787-96, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16101915

RESUMO

Costs of resistance are predicted to reduce plant productivity in herbicide-resistant weeds. Lolium rigidum herbicide-susceptible individuals (S), individuals possessing cytochrome P450-based herbicide metabolism (P450) and multiple resistant individuals possessing a resistant ACCase and enhanced cytochrome P450 metabolism (ACCase/P450) were grown in the absence of mutual plant interaction to estimate plant growth traits. Both P450 and ACCase/P450 resistant phenotypes produced less above-ground biomass than the S phenotype during the vegetative stage. Reduced biomass production in the resistant phenotypes corresponded to a reduced relative growth rate and a lower net assimilation rate and rate of carbon fixation. There were no significant differences between the two resistant phenotypes, suggesting that costs of resistance are associated with P450 metabolism-based resistance. There were no differences in reproductive output among the three phenotypes, indicating that the cost of P450 resistance during vegetative growth is compensated during the production of reproductive structures. The P450-based herbicide metabolism is shown to be associated with physiological resistance costs, which may be manipulated by agronomic management to reduce the evolution of herbicide resistance.


Assuntos
Acetil-CoA Carboxilase/genética , Sistema Enzimático do Citocromo P-450/genética , Herbicidas , Lolium/enzimologia , Lolium/genética , Biomassa , Resistência a Múltiplos Medicamentos/genética , Mutação , Fenótipo , Fotossíntese/genética , Fotossíntese/fisiologia , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento , Caules de Planta/crescimento & desenvolvimento , Sementes/genética , Sementes/fisiologia
8.
Clin Lab Haematol ; 24(3): 151-4, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12067278

RESUMO

In B-cell malignancies, it is generally held that the monoclonal components (MC) are produced by the malignant clones. Genetic relatedness implies the concordant expression of light-chain (LC) isotypes in the MC and at the surface of the malignant lymphocytes. We reviewed a series of 91 B-cell leukaemias, immunophenotyped by flow cytometry in our laboratory. A serum MC had been sought in 75 of these patients, and had been found in 23 (31%). Biclonal serum components were detected in three cases. LC concordance could not be assessed in three cases of surface LC-null lymphocytes. Of the 23 MC studied in 20 patients, light-chains were discordant in 39%, mostly due to kappa MC in lambda leukaemias. The origin of LC discordance remains speculative. It could be due to the emergence of subclones with the same primal VDJ gene rearrangement or, alternatively, to the development of new B-cell clones escaping immune surveillance from deregulated T-cells.


Assuntos
Cadeias Leves de Imunoglobulina , Leucemia de Células B/imunologia , Paraproteínas/análise , Idoso , Idoso de 80 Anos ou mais , Contagem de Linfócito CD4 , Células Clonais/imunologia , Feminino , Citometria de Fluxo , Humanos , Isotipos de Imunoglobulinas/análise , Subpopulações de Linfócitos , Masculino , Pessoa de Meia-Idade , Paraproteínas/imunologia
9.
Rev Med Brux ; 23 Suppl 2: 97-100, 2002.
Artigo em Francês | MEDLINE | ID: mdl-12584922

RESUMO

The Department of General Internal Medicine is devoted to the evaluation of patients with autoimmune systemic diseases, multiorganic disorders or presenting non specific symptoms such as chronic fatigue, unexplained weight loss or fever of unknown origin. The interest in salt and water metabolisms had led to original contributions in the treatment of hyponatremia in man and to the understanding of the osmotic demyelinating syndrome in a rat model of hyponatremia. The study of ageing in man and rodents had contributed to better understand lymphocyte and thyroid function in the elderly. The care for patients with various autoimmune disorders led to original observations in the pathogenicity of Sjögren's syndrome adult onset Still disease or sarcoidosis as well as the follow up of patients treated with azathioprine. Intensive collaboration with the Department of Immunology led to identify Th2 clonal lymphocytes as the cause of the so-called idiopathic hypereosinophilic syndrome in some patients and to define the clinical and biological features in this subset of patients.


Assuntos
Departamentos Hospitalares , Medicina Interna , Bélgica , Pesquisa Biomédica , Hospitais Universitários , Humanos
10.
Environ Mol Mutagen ; 36(2): 97-104, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11013407

RESUMO

A cDNA coding for rat cytochrome P450 2E1 was cloned into the multicopy vector pYeDP60 and expressed in haploid RSY6 and diploid RS112 yeast strains of Saccharomyces cerevisiae under control of the GAL10-CYC1 promoter. Spectral and catalytic properties of the expressed 2E1 were examined in whole cells or microsomes of both strains. The level of CYP2E1 obtained in RS112 (200 pmol/mg microsomal protein) was the highest among CYP2E1 produced in the various expression systems. The monooxygenase activity in the microsomes of both strains, measured as aniline hydroxylase, was found comparable to that of control rat hepatic microsomes. In a reconstituted system in the presence of exogenous rat P450 reductase, their activity increased about 10-fold. When exposed to the carcinogen NDMA, a known 2E1 substrate, the recombination frequency determined in the 2E1-expressing RS112 cells was enhanced, in a dose-dependent manner, up to 20-fold. The exposure of the same cells to the hepatotoxic solvents, N-methyl- and N-ethylformamide, resulted in an induction of recombination frequency, which was not observed in the void plasmid containing RS112 cells in the presence of S9 hepatic fractions from pyrazole-induced rats, as a specific exogenous metabolic activation system. These results demonstrate that the 2E1-expressing cells metabolize the two N-alkylformamides to genotoxic intermediates and, therefore, they provide an useful tool to study the bioactivation mechanism of potential P450 2E1 substrates.


Assuntos
Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Formamidas/toxicidade , Saccharomyces cerevisiae/genética , Testes de Toxicidade/métodos , Animais , Biotransformação , Clonagem Molecular , Citocromo P-450 CYP2E1/efeitos dos fármacos , Formamidas/farmacocinética , Vetores Genéticos , Masculino , Compostos Nitrosos/toxicidade , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Recombinação Genética , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/enzimologia
11.
Rev Med Brux ; 21(3): 161-3, 2000 Jun.
Artigo em Francês | MEDLINE | ID: mdl-10925598

RESUMO

The authors report the case of a patient who developed a serotonin syndrome after taking sertraline and metoclopramide. The symptoms included malaise, cardiac arrhythmia, sudation, hyperreflexia, sialosis, diarrhea and were improved by cyproheptadine. The authors review the physiological bases of the serotonin syndrome, its incidence, clinical manifestations and treatment.


Assuntos
Antieméticos/efeitos adversos , Metoclopramida/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Síndrome da Serotonina/induzido quimicamente , Sertralina/efeitos adversos , Adulto , Ciproeptadina/uso terapêutico , Combinação de Medicamentos , Humanos , Masculino , Antagonistas da Serotonina/uso terapêutico , Síndrome da Serotonina/tratamento farmacológico , Síndrome da Serotonina/fisiopatologia
12.
IEEE Trans Image Process ; 9(11): 1995-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-18262937

RESUMO

This paper shows that an n x 1 integer vector can be exactly recovered from its Hadamard transform coefficients, even when 0.5 n log(2)(n) of the (less significant) bits of these coefficients are removed. The paper introduces a fast "lossless" dequantization algorithm for this purpose. To investigate the usefulness of the procedure in data compression, the paper investigates an embedded block image coding technique called the "LHAD" based on the algorithm. The results show that lossless compression ratios close to the state of the art can be achieved, but that techniques such as CALIC and S+P still perform better.

13.
Cell Tissue Res ; 294(1): 125-35, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9724462

RESUMO

We have shown that large lysosomes appear in thyroids of aging male cream hamsters. To investigate the role of this lysosomal change in the age-dependent reduction in hormone secretion, thyroids of young (<4 months of age) and old (>22 months of age) male and female hamsters were labeled with 125I at near isotopic equilibrium. Changes in thyroid morphology were analyzed by light- and electron-microscopic morphometry. Changes in thyroglobulin processing were analyzed by subcellular fractionation and identification of 125I-compounds by sucrose gradients and reverse-phase high-pressure liquid chromatography (HPLC). Sexual dimorphism present in thyroids of young animals became more marked upon aging. The parallel increase in thyroid weight and thyroglobulin content was more conspicuous in old females than in old males. Two morphological observations were specific to old females: (1) large follicles with flat epithelium and evenly labeled colloid and (2) deposits of amyloid material (possibly immunoglobulin light chain-related) between follicles. Although lysosomes were enlarged in female and male aged thyroids, they did not accumulate iodine. However, after isopycnic centrifugation of crude lysosomal fractions in Percoll gradients, 125I in old thyroids was not distributed mainly in the dense fraction L1 (lysosomes) as in young thyroids, but partly in particles of lower density (light L2 and buoyant fractions). 125I in the lighter particles was mostly found in intact thyroglobulin and in large iodopeptides. This 125I shift towards less dense particles was more marked in females than in males. These results indicate that age delays thyroglobulin progression towards dense lysosomes and suggest that the slower traffic of thyroglobulin in the endocytic pathway contributes to the reduction in thyroid hormone secretion in the aged cream hamster.


Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Lisossomos/ultraestrutura , Glândula Tireoide/metabolismo , Glândula Tireoide/ultraestrutura , Hormônios Tireóideos/metabolismo , Amiloide/metabolismo , Animais , Cricetinae , Endocitose , Endossomos/ultraestrutura , Feminino , Hidrólise , Iodo/metabolismo , Radioisótopos do Iodo , Masculino , Microscopia Eletrônica , Caracteres Sexuais , Tireoglobulina/metabolismo
15.
Leukemia ; 11 Suppl 1: S19-23, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9130687

RESUMO

There is no standard therapy for elderly patients with high-risk myelodysplastic syndrome (MDS). The treatment options of low-dose Ara-C and haematopoietic growth factors are disappointing in regard to response rate or response duration. We tested the treatment with a 72-h continuous infusion of low-dose 5-Aza-2'-deoxycytidine (DAC) in a group of 29 elderly patients with high-risk MDS. In 15 patients (54%) we observed a response. Eight complete responses were reached, even among patients with bad prognostic cytogenetic findings. The actuarial median survival from the start of the therapy was 46 weeks. The only (and major) toxicity was myelosuppression, leading to a prolonged cytopenic period and thus leading to five toxic deaths (17%) in this high-risk patient group. We conclude that DAC is an effective drug in the treatment of MDS patients and that it probably works via its cytotoxic activity. Myelotoxicity is its major adverse effect.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/análogos & derivados , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Azacitidina/uso terapêutico , Medula Óssea/patologia , Decitabina , Contagem de Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Infusões Intravenosas , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Morbidade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Contagem de Plaquetas/efeitos dos fármacos , Prognóstico , Medição de Risco , Taxa de Sobrevida
16.
Ann Hematol ; 74(3): 149-53, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9111430

RESUMO

A particular case of marginal zone B-cell lymphoma (MZBCL) presenting with leukemic lymphocytes is reported. In the present observation, the leukemic cells not only displayed a remarkable morphological fluctuation but also had an unusual phenotype, changing with time. These phenotypic features, which have been functionaly investigated by in vitro assays, might simply reflect an activation state depending on the microenvironment. Because of its disconcerting similarities with hairy cell leukemia (HCL) and splenic lymphoma with villous lymphocytes (SLVL), this case relaunches the debate about whether close relationships might exist between the splenic marginal zone, SLVL and HCL.


Assuntos
Leucemia/genética , Leucemia/patologia , Linfoma de Células B/genética , Linfoma de Células B/patologia , Antígenos CD19/análise , Linfócitos B/imunologia , Heterogeneidade Genética , Humanos , Leucemia de Células Pilosas/patologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo
17.
Leuk Lymphoma ; 24(5-6): 545-51, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9086445

RESUMO

Little is known about the function of the T lymphocytes in lymphocyte predominance Hodgkin's disease. We report here the case of a 37-year-old man with a diffuse LPHD, featuring a similar increase in T lymphocytes in both the peripheral blood and the tumor, thus allowing for their characterization by functional assays. These cells were CD4+CD45RO+ and produced high amounts of IL-2 and IFN-gamma, consistent with a TH1-type profile. This subset of T helper cells is involved in cellular immunity and could reflect a cytotoxic reaction directed against the neoplastic cells.


Assuntos
Doença de Hodgkin/patologia , Linfócitos T/fisiologia , Adulto , Antígenos CD/análise , Citometria de Fluxo , Doença de Hodgkin/sangue , Doença de Hodgkin/imunologia , Humanos , Imunidade Celular/fisiologia , Interferon gama/biossíntese , Interleucina-2/biossíntese , Ativação Linfocitária , Masculino , Linfócitos T/imunologia , Linfócitos T/metabolismo
18.
Leukemia ; 11(1): 1-5, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9001409

RESUMO

There is no standard therapy for elderly patients with high-risk myelodysplastic syndrome (MDS). The treatment options of low-dose Ara-C and haematopoietic growth factors are disappointing in regard to response rate or response duration. We tested the treatment with a 72-h continuous infusion of low-dose 5-Aza-2'-deoxycytidine (DAC) in a group of 29 elderly patients with high-risk MDS. In 15 patients (54%) we observed a response. Eight complete responses were reached, even among patients with bad prognostic cytogenetic findings. The actuarial median survival from the start of the therapy was 46 weeks. The only (and major) toxicity was myelosuppression, leading to a prolonged cytopenic period and thus leading to five toxic deaths (17%) in this high-risk patient group. We conclude that DAC is an effective drug in the treatment of MDS patients and that it probably works via its cytotoxic activity. Myelotoxicity is its major adverse effect.


Assuntos
Antineoplásicos/uso terapêutico , Azacitidina/análogos & derivados , Síndromes Mielodisplásicas/tratamento farmacológico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária/tratamento farmacológico , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Antineoplásicos/efeitos adversos , Azacitidina/efeitos adversos , Azacitidina/uso terapêutico , Decitabina , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide/tratamento farmacológico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pancitopenia/induzido quimicamente
19.
Eur J Cell Biol ; 68(4): 437-45, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8690023

RESUMO

In chronically stimulated rat thyroids after subtotal thyroidectomy, lysosomes increased in number and volume. They contained iodocompounds and did not appear in iodine-deficient animals. In this study, we analyzed the subcellular localization and the nature of these intracellular iodocompounds. Classical subcellular fractions were isolated from homogenates of rat thyroids and remnants 14 weeks after sham-operation or subtotal thyroidectomy. Two lysosome subpopulations of increasing density, a light fraction, lysosomes 2 (L2, density 1.065-1.08 g/ml) and a dense fraction, lysosomes 1 (L1, density > 1.08 g/ml) were separated from crude lysosomal particulate fractions (ML) by centrifugation in Percoll gradients. Results obtained with thyroids of normal rats were used as controls. In TSH-stimulated thyroid remnants, total activities of three lysosomal enzymes and iodine concentration were increased by 1.6-fold compared with thyroids of sham-operated rats. Total iodoprotein-derived T3 and T4 concentrations, measured after pronase hydrolysis, were slightly decreased. Thyroglobulin (Tg) concentration in the supernatant was reduced by 50%. Iodine, T3 and T4 contents of Tg were not modified. After differential centrifugation, the iodine excess of remnants sedimented with subcellular particulate fractions. The concentration of iodine in dense lysosomes (L1) was 6 times that in sham L1. Intact Tg did not accumulate in L1. Two thirds of the iodine in L1 was soluble in methanol, double the normal proportion, with twice as much iodine included in hydrophobic peptides eluted after T4 by reverse-phase HPLC. Although iodoprotein-derived T4 and T3 concentrations were decreased in the remnant homogenate, they were increased in particles, particularly in L1 where they were increased by 8 and 4-fold, respectively. In contrast, specific activities of lysosomal enzymes in ML and L1 remained unchanged. It is concluded that the chronic TSH stimulation of thyroid remnants in subthyroidectomized rats receiving a normal iodine supply induces the endocytosis of a normal Tg with iodine kept in dense lysosomes. The expansion of the lysosomal compartment resulted from a limitation in iodopeptides degradation as though secondary lysosomes would be overloaded with Tg. The accumulation in L1 of hydrophobic iodopeptides and of more iodoprotein-derived T4 than T3 suggests that exopeptidases involved in the liberation of T4 become rate-limiting.


Assuntos
Iodo/análise , Lisossomos/química , Glândula Tireoide/química , Animais , Cromatografia Líquida de Alta Pressão , Lisossomos/enzimologia , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Tireoglobulina/análise , Glândula Tireoide/fisiologia , Glândula Tireoide/ultraestrutura , Tireoidectomia , Tiroxina/análise , Tri-Iodotironina/análise
20.
Mech Ageing Dev ; 85(2-3): 147-59, 1995 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-8786661

RESUMO

Using anti-CD5 and anti-SIgM fluorescent monoclonal antibodies, four subsets of lymphocytes can be distinguished in CBA mice, SIgM+ (T2) and SIgM- (T1) T lymphocytes and, CD5+ (B1) and CD5- (B2) B lymphocytes. L3T4 anti-CD4 and Lyt2 anti-CD8 positivities delineate two major T lymphocyte subsets. The cell size of these subsets has been evaluated by their forward light scatter in flow cytometry after cell fixation. The mean cell size of the different subsets differs, according to subset, age and vitamin E treatment. Globally, there is an age-related increase in size for all subsets. In vitamin-E treated young animals, all subsets are smaller, and the percentages of the biggest B1 and B2 cells decrease. In old mice, the vitamin-E effect is far more variable. B2 cells tend to increase in size but the percentage of the biggest cells diminishes. On the contrary, there is a marked expansion of the large B1 cells. No effect is discernible on CD5+ T lymphocytes, but L3T4 and Lyt2 subpopulations increase in size. This study is a retrospective one and the mechanisms affecting cell size are speculative. Since the lymphocyte cell size was measured after fixation in an hypertonic medium devised for human blood processing, we cannot differentiate a real size modification from a differential volume resistance to experimental conditions. Whatever the case, the changes in cell volume argue for age-related changes in cell membrane permeability and volume homeostasis. For some subsets, cell activation and consequent size increase must also be considered. As far as vitamin E has marked anti-oxidant properties, its effect on cell size provides indirect evidence for a role of free radicals in the observed changes and gives support to the oxidant stress theory of ageing in immune senescence.


Assuntos
Envelhecimento/fisiologia , Tamanho Celular/efeitos dos fármacos , Linfócitos/classificação , Vitamina E/farmacologia , Animais , Dieta , Camundongos , Camundongos Endogâmicos
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