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1.
BMC Neurol ; 21(1): 90, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33632158

RESUMO

BACKGROUND: The primary symptoms of restless legs syndrome (RLS) are sleep onset insomnia and difficulty to maintain sleep. Previous studies have shown that regular physical activity can reduce the risk of developing RLS. However, the relationship between physical activity and sleep quality parameters in individuals suffering from RLS has not yet been investigated by applying accelerometry. Thus, the present study investigates the impact of physical activity (measuring both intensity levels and duration of physical activity) during the day (7-12 h, 12-18 h, 18-23 h) on sleep quality in patients suffering from idiopathic RLS by applying a real-time approach. METHODS: In a sample of 47 participants suffering from idiopathic RLS, physical activity and sleep quality were measured over one week using accelerometers. For data analysis, physical activity levels and step counts during three periods of the day (morning, afternoon, evening) were correlated with sleep quality parameters of the subsequent night. RESULTS: This observational study revealed that in most instances physical activity was not correlated with sleep parameters (two exceptions exist: steps taken in the morning were negatively correlated with periodic leg movements during sleep, and physical activity in the evening was negatively correlated with total sleep time). The physical activity levels of the participants in this study, however, were unexpectedly high compared to population-level data and variance in physical activity was low. The average activity was 13,817 (SD = 4086) steps and 347 (SD = 117) minutes of moderate physical activity per day in females, and 10,636 (SD = 3748) steps and 269 (SD = 69) minutes of moderate physical activity in males, respectively. Participants did not engage in any vigorous physical activity. CONCLUSIONS: Further interventional studies are needed to investigate the daily effects of different intensities of physical activity on RLS symptoms.


Assuntos
Exercício Físico , Síndrome das Pernas Inquietas , Distúrbios do Início e da Manutenção do Sono , Acelerometria , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Síndrome das Pernas Inquietas/complicações , Distúrbios do Início e da Manutenção do Sono/etiologia
3.
Acta Biomater ; 65: 475-485, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29107056

RESUMO

In this study a premixed strontium-containing calcium phosphate bone cement for the application in osteoporotic bone defects has been developed and characterised regarding its material and in vitro properties as well as minimally invasive applicability in balloon kyphoplasty. Strontium was introduced into the cement by substitution of one precursor component, CaCO3, with its strontium analogue, SrCO3. Using a biocompatible oil phase as carrier liquid, a cement paste that only set upon contact with aqueous environment was obtained. Strontium modification resulted in an increased strength of set cements and radiographic contrast; and the cements released biologically relevant doses of Sr2+-ions that were shown to enhance osteoprogenitor cell proliferation and osteogenic differentiation. Finally, applicability of strontium-containing cement pastes in balloon kyphoplasty was demonstrated in a human cadaver spine procedure. The cement developed in this study may therefore be well suited for minimally invasive, osteoporosis-related bone defect treatment. STATEMENT OF SIGNIFICANCE: Strontium-releasing calcium phosphate bone cements are promising materials for the clinical regeneration of osteoporosis-related bone defects since they have been shown to stimulate bone formation and at the same time limit osteoclastic bone resorption. Today clinical practice favours minimally invasive surgical techniques, e.g. for vertebral fracture treatment, posing special demands on such cements. We have therefore developed a premixed, strontium-releasing bone cement with enhanced mechanical properties and high radiographic visibility that releases biologically relevant strontium concentrations and thus stimulates cells of the osteogenic lineage. In a pilot experiment we also exemplify its excellent suitability for minimally invasive balloon kyphoplasty procedures.


Assuntos
Cimentos Ósseos/uso terapêutico , Fosfatos de Cálcio/uso terapêutico , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Estrôncio/química , Idoso , Cadáver , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Adesão Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Microscopia Eletrônica de Varredura , Projetos Piloto
4.
Nervenarzt ; 85(12): 1521-8, 2014 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-25380564

RESUMO

BACKGROUND: Physical activity has beneficial effects on somatic and mental health factors; therefore, regular exercise has preventive and therapeutic capabilities to improve neurological and mental dysfunction. OBJECTIVES: In this overview of the current literature, the evidence of the effects of exercise on such disorders is summarized. Physical exercise interventions for stroke, Parkinson's disease, dementia, depression, psychoses, anxiety disorders, and chronic pain syndromes are considered in detail. RESULTS: Physical activity reduces the risk of suffering from stroke, dementia and Parkinson's disease. Furthermore, it is negatively correlated with dysthymia and other depressive symptoms and various anxiety and pain disorders as well as headache syndromes. A therapeutic effect of systematic physical exercise was revealed for depression, some symptoms of psychosis and multiple sclerosis, addiction, eating disorders, the fibromyalgia syndrome as well as short-term interventions for anxiety disorders. CONCLUSION: The concerted integration of physical exercise into prophylactic and therapeutic interventions can lower the burden of neurological and mental diseases; however, scientific evidence is still lacking concerning the optimal duration, type, and intensity as well as potential risks of physical exercise.


Assuntos
Terapia por Exercício/métodos , Transtornos Mentais/terapia , Doenças do Sistema Nervoso/terapia , Condicionamento Físico Humano/métodos , Comportamento de Redução do Risco , Medicina Baseada em Evidências , Humanos , Transtornos Mentais/diagnóstico , Doenças do Sistema Nervoso/diagnóstico , Resultado do Tratamento
5.
J Aging Res ; 2012: 243958, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22811911

RESUMO

Physical activity reduces many major mortality risk factors including arterial hypertension, diabetes mellitus type 2, dyslipidemia, coronary heart disease, stroke, and cancer. All-cause mortality is decreased by about 30% to 35% in physically active as compared to inactive subjects. The purpose of this paper was to synthesize the literature on life expectancy in relation to physical activity. A systematic PubMed search on life expectancy in physically active and inactive individuals was performed. In addition, articles comparing life expectancy of athletes compared to that of nonathletes were reviewed. Results of 13 studies describing eight different cohorts suggest that regular physical activity is associated with an increase of life expectancy by 0.4 to 6.9 years. Eleven studies included confounding risk factors for mortality and revealed an increase in life expectancy by 0.4 to 4.2 years with regular physical activity. Eleven case control studies on life expectancy in former athletes revealed consistently greater life expectancy in aerobic endurance athletes but inconsistent results for other athletes. None of these studies considered confounding risk factors for mortality. In conclusion, while regular physical activity increases life expectancy, it remains unclear if high-intensity sports activities further increase life expectancy.

6.
Int J Sports Med ; 30(3): 213-24, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19199202

RESUMO

In a meta-analysis we investigated the effect of physical activity with different intensity categories on all-cause mortality. Many studies have reported positive effects of regular physical activity on primary prevention. This recent meta-analysis analyzed all-cause mortality with special reference to intensity categories. A computerized systematic literature search was performed in EMBASE, PUBMED, and MEDLINE data bases (1990-2006) for prospective cohort studies on physical leisure activity. Thirty-eight studies were identified and evaluated. The presentation refers to studies with 3 or 4 different intensities of regular physical activity according to a standard questionnaire. There was a significant association of lower all-cause mortality for active individuals compared with sedentary persons. For studies with three activity categories (mildly, moderately, and highly active) and multivariate-adjusted models, highly active men had a 22% lower risk of all-cause mortality (RR=0.78; 95% CI: 0.72 to 0.84) compared to mildly active men. For women, the relative risk was 0.69 (95% CI: 0.53 to 0.90). We observed similar results in moderately active persons compared to mildly active individuals (RR=0.81 for men and RR=0.76 for women). This association of activity to all-cause mortality was similar and significant in older subjects. Regular physical activity over longer time is strongly associated with a reduction in all-cause mortality in active subjects compared to sedentary persons. There is a dose-response curve especially from sedentary subjects to those with mild and moderate exercise with only a minor additional reduction with further increase in activity level.


Assuntos
Mortalidade , Atividade Motora/fisiologia , Aptidão Física/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Atividades de Lazer , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Risco , Comportamento de Redução do Risco , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
7.
Nature ; 426(6964): 261-4, 2003 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-14628044

RESUMO

Stars with masses in the range 1-8 solar masses (M(\circ)) live ordinary lives for approximately 10(9)-10(10) years, but die extraordinary deaths. First, during their death throes as asymptotic giant branch (AGB) stars they eject, over 10(4)-10(5) years, half or more of their mass in slowly expanding, spherical winds, and then, in a short (a few 100-1,000 years) and poorly understood phase, they are transformed into aspherical planetary nebula. Recent studies support the idea that high-speed, jet-like flows play a crucial role in this transformation. Evidence for such outflows is indirect, however; this phase is so short that few nearby stars are likely to be caught in the act. Here we report the discovery of a newly launched, high-speed jet-like outflow in the nearby AGB star, V Hydrae. We have detected both proper motions and ongoing evolution in the jet. These results support a model in which the jet is driven by an accretion disk around an unseen, compact companion. We also find a central, dense equatorial disk-like structure which may enable and/or enhance the formation of the accretion disk.

8.
Anal Bioanal Chem ; 376(5): 715-20, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12802569

RESUMO

The High Pressure Asher (HPA-S) was adapted with a Teflon liner for pressurized wet digestion in open vessels. The autoclave was partly filled with water containing 5% (vol/vol) hydrogen peroxide. The digestion vessels dipped partly into the water or were arranged on top of the water by means of a special rack made of titanium or PTFE-coated stainless steel. The HPA-S was closed and pressurized with nitrogen up to 100 bars. The maximum digestion temperature was 250 degrees C for PFA vessels and 270 degrees C for quartz vessels. Digestion vessels made of quartz or PFA-Teflon with volumes between 1.5 mL (auto sampler cups) and 50 mL were tested. The maximum sample amount for quartz vessels was 0.5-1.5 g and for PFA vessels 0.2-0.5 g, depending on the material. Higher sample intake may lead to fast reactions with losses of digestion solution. The samples were digested with 5 mL HNO(3) or with 2 mL HNO(3)+6 mL H(2)O+2 mL H(2)O(2). The total digestion time was 90-120 min and 30 min for cooling down to room temperature. Auto sampler cups made of PFA were used as digestion vessels for GFAAS. Sample material (50 mg) was digested with 0.2 mL HNO(3)+0.5 mL H(2)O+0.2 mL H(2)O(2). The analytical data of nine certified reference materials are also within the confidential intervals for volatile elements like mercury, selenium and arsenic. No cross contamination between the digestion vessels could be observed. Due to the high gas pressure, the diffusion rate of volatile species is low and losses of elements by volatilisation could be observed only with diluted nitric acid and vessels with large cross section. In addition, cocoa, walnuts, nicotinic acid, pumpkin seeds, lubrication oil, straw, polyethylene and coal were digested and the TOC values measured. The residual carbon content came to 0.2-10% depending on the sample matrix and amount.

9.
Anal Bioanal Chem ; 372(7-8): 801-7, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12012192

RESUMO

Sequential extraction procedures are mostly applied to soils and sediments. Investigations were made for testing the applicability of a selected extraction scheme on spoil pile material. Therefore, different spoil pile samples from uranium mining were extracted into four steps (exchangeable, reducible, oxidizable, and aqua regia soluble phase) and the contents of the elements Cr, Cu, Fe, K, Ni, and Zn were analyzed. To substitute the sequential extraction by a sequence of single extractions and thus keep uncertainties of extraction on a low level, both procedures were compared regarding conformity of their results. The effects of sample handling as well as those of analysis on the measured metal contents were determined by means of analysis of variance and sources of uncertainties were discussed.

10.
Scand J Gastroenterol ; 36(9): 934-41, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11521983

RESUMO

BACKGROUND: Dyspeptic symptoms are commonly reported complaints in clinical practice and are mostly the result of functional disorders. Empirical treatment with histamine H2-receptor blockers or gastroprokinetics for 2-4 weeks has frequently been proposed as first line management of these patients. The clinical trials which support the use of these agents, show a high variation in clinical success rate and benefit of these treatments. METHODS: The available clinical trials were evaluated, pooled where appropriate and subjected to a meta-analysis with the principal goal to provide valid treatment recommendations for patients with non-ulcer dyspepsia. In the present meta-analysis 19 studies on gastroprokinetics (cisapride, domperidone) and 10 studies on histamine H2-receptor antagonists (cimetidine, ranitidine) were included. RESULTS: Based on these studies, a total of 1540 patients were evaluated for histamine H2-receptor antagonists (verum n = 786, placebo n = 754) and 1235 patients for gastroprokinetics (verum n = 616, placebo n = 619). The probability for treatment success compared to placebo was 0.2026 (0.1261; 0.2791) for histamine H2-receptor antagonists and 0.4029 (0.3042; 0.5069) for gastroprokinetics. CONCLUSIONS: Based on these data both treatments are significantly more effective than placebo in the symptomatic treatment of non-ulcer dyspepsia, with gastroprokinetics (cisapride, domperidone) being more effective than histamine H2-receptor antagonists (cimetidine, ranitidine).


Assuntos
Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Cimetidina/uso terapêutico , Cisaprida/uso terapêutico , Domperidona/uso terapêutico , Humanos , Ranitidina/uso terapêutico , Projetos de Pesquisa
11.
Stat Med ; 20(12): 1771-82, 2001 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-11406840

RESUMO

For the meta-analysis of controlled clinical trials or epidemiological studies, in which the responses are at least approximately normally distributed, a refined test for the hypothesis of no overall treatment effect is proposed. The test statistic is based on a direct estimation function for the variance of the overall treatment effect estimator. As outcome measures, the absolute and the standardized difference between means are considered. In simulation studies it is shown that the proposed test keeps the prescribed significance level very well in contrast to the commonly used tests in the fixed effects and random effects model, respectively, which can become very liberal. Furthermore, just for using the proposed test it is not necessary to choose between the fixed effects and the random effects approach in advance.


Assuntos
Ensaios Clínicos Controlados como Assunto/métodos , Metanálise como Assunto , Estatística como Assunto/métodos , Anlodipino/uso terapêutico , Angina Pectoris/tratamento farmacológico , Simulação por Computador , Exercício Físico/fisiologia , Humanos , Resultado do Tratamento , Vasodilatadores/uso terapêutico
12.
Anal Chem ; 73(7): 1515-20, 2001 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11321303

RESUMO

A novel, microwave-assisted, high-temperature UV digestion procedure was developed for the accelerated decomposition of interfering dissolved organic carbon (DOC) prior to trace element analysis of liquid samples such as, industrial/municipal wastewater, groundwater, and surface water, body fluids, infusions, beverages, and sewage. The technique is based on a closed, pressurized, microwave digestion device. UV irradiation is generated by immersed electrodeless Cd discharge lamps (228 nm) operated by the microwave field in the oven cavity. To enhance excitation efficiency an antenna was fixed on top of the microwave lamp. The established immersion system enables maximum reaction temperatures up to 250-280 degrees C, resulting in a tremendous increase of mineralization efficiency. Compared to open UV digestion devices, decomposition time is reduced by a factor of 5 and the maximum initial concentration of DOC can be raised by at least a factor of 50. The system's performance on a real-type sample was evaluated for the mineralization of skimmed milk (IRMM, CRM 151) and subsequent determination of trace elements using standard spectroscopic techniques. Recovery for Cd (109%), Cu (112%), Fe (99%), and Pb (96%) showed good agreement with the 95% confidence interval of the certified values.


Assuntos
Oligoelementos/análise , Animais , Micro-Ondas , Leite/química , Oxirredução , Temperatura , Raios Ultravioleta
13.
Stat Med ; 20(24): 3875-89, 2001 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-11782040

RESUMO

For the meta-analysis of controlled clinical trials with binary outcome a test statistic for testing an overall treatment effect is proposed, which is based on a refined estimator for the variance of the treatment effect estimator usually used in the random-effects model of meta-analysis. In simulation studies it is shown that the proposed test keeps the prescribed significance level much better than the commonly used tests in the fixed-effects and random-effects model, respectively. Moreover, when using the test it is not necessary to choose between fixed effects and random effects approaches in advance. The proposed method applies in the same way to the analysis of a controlled multi-centre study with binary outcome, including a possible interaction between drugs and centres.


Assuntos
Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Cisaprida/uso terapêutico , Simulação por Computador , Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Humanos
14.
Antimicrob Agents Chemother ; 44(11): 3210-2, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11036056

RESUMO

Many laboratory strains of Escherichia coli are resistant to methotrexate (MTX), a folate analogue that binds dihydrofolate reductase (DHFR). Mutations that inactivate either tolC or acrA confer MTX sensitivity. Further, overexpression of a fusion protein with DHFR activity reverses this sensitivity by titrating out intracellular MTX. These results suggest that MTX accumulates in cells where mutations in acrA or tolC have inactivated the TolC-dependent AcrAB multidrug resistance efflux pump.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Proteínas de Bactérias/metabolismo , Inibidores Enzimáticos/farmacologia , Proteínas de Escherichia coli , Escherichia coli/efeitos dos fármacos , Lipoproteínas/metabolismo , Metotrexato/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/genética , Transporte Biológico , Resistência Microbiana a Medicamentos/fisiologia , Escherichia coli/enzimologia , Escherichia coli/metabolismo , Antagonistas do Ácido Fólico/farmacologia , Lipoproteínas/genética , Proteínas de Membrana Transportadoras , Mutação , Tetra-Hidrofolato Desidrogenase/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-11187570

RESUMO

Concerning the actual significance level, we investigate the commonly used combined test procedures of meta-analysis, which contain the choice of the model, in which the analysis is carried out, and the commonly used tests for treatment effect in the fixed and random effects model, and some new combined test procedures, which use an alternative test statistic in the random effects model or the t-distribution as test distribution of the commonly used test statistics. A simulation study indicates that the new combined test procedures are better with respect to a prescribed significance level.


Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Metanálise como Assunto , Simulação por Computador , Humanos , Computação Matemática , Modelos Estatísticos
16.
Fresenius J Anal Chem ; 366(1): 26-9, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11225810

RESUMO

Investigations of microwave assisted drying of sample materials and microwave assisted evaporation of aqueous sample solutions and acidic digestion residues were accomplished by means of special rotors for the microwave digestion system MULTIWAVE. To check the results obtained by microwave assisted drying, the samples were also conventionally dried at 105 degrees C in an oven. The following samples have been dried: 10 g each of meat, fish, apple, cucumber, potato, mustard, yogurt, clay and marl; 1 g each of certified reference material TORT 2 (lobster hepatopancreas), BCR 278 (mussel tissue) and BCR 422 (cod muscle); 500 g garden mould. Microwave assisted drying takes 40 min for organic samples and 30 min for inorganic material. Important is a slow increase of microwave power during the first 20 min. The results agree well with conventional drying at 105 degrees C. Losses of As, Se and Hg have been investigated for 3 CRMs. Only Se shows losses in the range of 20%. Losses of As, Be, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn, Mo, Ni, Pb, Sb, Se, Sr, Ti, Tl, V and Zn after evaporation of aqueous samples and acidic solutions after wet digestion, respectively, have been investigated. 50 mL aqueous solution was evaporated almost to dryness within 25 min. The recovery of Hg is 40-50%, of Se 90-95% and of the other elements 97-102%. 0.2 g each of TORT 2, BCR 278 and BCR 422 have been digested with 4 mL nitric acid and 1 mL hydrochloric acid by means of the microwave digestion system MULTIWAVE. The digestion residue was evaporated almost to dryness and dissolved again in 10 mL diluted nitric acid. In this case no element losses have been observed. The measured concentration of As, Cd, Cu, Fe, Mn, Hg, Pb, Mo, Ni, Se, Sr, V and Zn agree very well with the certified values. An important prerequisite for good recoveries is not to evaporate the solutions to complete dryness.


Assuntos
Dessecação/métodos , Micro-Ondas , Oligoelementos/análise , Ácidos/química , Padrões de Referência
17.
J Synchrotron Radiat ; 7(Pt 2): 53-60, 2000 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-16609174

RESUMO

In the period of the late-1980s, before the construction of multi-GeV third-generation storage rings with their intense insertion-device sources, the perceived number one problem for X-ray instrumentation was proper cooling of the first optical element in the beamline. This article, first given as an acceptance speech for the Compton Award ceremony at the Advanced Photon Source, presents a somewhat historical and anecdotal overview of how cryogenically cooled monochromator optics have been developed to provide a monochromator cooling solution adequate for today's power levels. A series of workshops and international collaborations were the key components for the progress and final success of this development.

18.
Pneumologie ; 53(9): 411-6, 1999 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-10544649

RESUMO

By a re-analysis of the Blue Mountains Eye Study of Cumming, Mitchell and Leeder, Published in N Engl J Med 1997 (337: 8-14), there is shown in the present article, that this study does not yield a contribution to clarify the question, whether the use of inhaled corticosteroids is associated with the development of cataracts. The conclusions of the study are revealed to lead to results contradicting known risk factors.


Assuntos
Corticosteroides/efeitos adversos , Catarata/induzido quimicamente , Administração por Inalação , Corticosteroides/administração & dosagem , Asma/tratamento farmacológico , Catarata/epidemiologia , Protocolos Clínicos , Humanos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco
19.
Mutat Res ; 431(2): 291-303, 1999 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-10635995

RESUMO

We used a direct polymerase chain reaction (PCR) method for quantification of HPRT exons 2 + 3 deletions and t(14;18) translocations as a measure of illegitimate V(D)J recombination. We determined the baseline frequencies of these two mutations in mononuclear leukocyte DNA from the umbilical cord blood of newborns and from the peripheral blood of adults. In an initial group of 21 newborns, no t(14;18) translocations were detected (< 0.049 x 10(-7)). The frequency of HPRT exons 2 + 3 deletions was 0.10 x 10(-7) per mononuclear leukocyte, lower than expected based on the T-cell proportion of this cell fraction (55%-70%) and previous results using the T-cell cloning assay (approximately 2-3 x 10(-7) per clonable T-cell). Phytohemagglutinin (PHA), as used in the T-cell cloning assay, was examined for its effect on the frequencies of these mutation events in mononuclear leukocytes from an additional 11 newborns and from 12 adults. There was no significant effect of PHA on t(14;18) translocations which were rare among the newborns (1 detected among 2.7 x 10(8) leukocytes analyzed), and which occurred at frequencies from < 1 x 10(-7) (undetected) to 1.6 x 10(-4) among the adults. The extremely high frequencies of t(14;18)-bearing cells in three adults were due mainly to in vivo expansion of two to six clones. However, PHA appeared to stimulate a modest (although not significant) increase in the frequency of HPRT exons 2 + 3 deletions in the leukocytes of the newborns, from 0.07 x 10(-7) to 0.23 x 10(-7). We show that both the direct PCR assay and the T-cell cloning assay detect similar frequencies of HPRT exons 2 + 3 deletions when calculations are normalized to blood volume, indicating that the apparent discrepancy is probably due to the different population of cells used in the assays. This direct PCR assay may have utility in characterizing the effects of environmental genotoxic agents on this clinically important recombination mechanism.


Assuntos
DNA Nucleotidiltransferases/metabolismo , Hipoxantina Fosforribosiltransferase/genética , Linfócitos/fisiologia , Mutação , Adulto , Sequência de Bases , Quebra Cromossômica , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , DNA Nucleotidiltransferases/efeitos dos fármacos , Éxons , Feminino , Sangue Fetal/fisiologia , Humanos , Hipoxantina Fosforribosiltransferase/efeitos dos fármacos , Hipoxantina Fosforribosiltransferase/metabolismo , Recém-Nascido , Linfócitos/efeitos dos fármacos , Dados de Sequência Molecular , Fito-Hemaglutininas/farmacologia , Reação em Cadeia da Polimerase/métodos , Deleção de Sequência , Translocação Genética , VDJ Recombinases
20.
Mol Cell Neurosci ; 12(4-5): 220-7, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9828087

RESUMO

When C57BL/6J mice, 8 weeks of age, received 0.2% Cuprizone in their diet, extensive demyelination in corpus callosum was detectable after 3 weeks, and there was massive demyelination by 4 weeks. As expected, the accumulation of phagocytically active microglia/macrophages correlated closely with demyelination. When Cuprizone was removed from the diet, remyelination was soon initiated; after 6 weeks of recovery, myelin levels were near-normal and phagocytic cells were no longer prominent. Steady-state levels of mRNA for myelin-associated glycoprotein, myelin basic protein, and ceramide galactosyltransferase were already profoundly depressed after 1 week of Cuprizone exposure and were only 10-20% of control values after 2 weeks. Unexpectedly, upregulation of mRNA for these myelin genes did not correlate with initiation of remyelination but rather with accumulation of microglia/macrophages. After 6 weeks of exposure to Cuprizone, mRNA levels were at control levels or higher-in the face of massive demyelination. This suggests that in addition to effecting myelin removal, microglia/macrophages may simultaneously push surviving oligodendroglia or their progenitors toward myelination.


Assuntos
Encéfalo/metabolismo , Cuprizona/toxicidade , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas da Mielina/genética , Bainha de Mielina/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/patologia , Cuprizona/administração & dosagem , Doenças Desmielinizantes/induzido quimicamente , Dieta , Galactosiltransferases/genética , Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Microglia/fisiologia , Proteína Básica da Mielina/genética , Bainha de Mielina/patologia , Bainha de Mielina/ultraestrutura , Glicoproteína Associada a Mielina/genética , N-Acilesfingosina Galactosiltransferase , Fagocitose , RNA Mensageiro/genética , Transcrição Gênica
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