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2.
Reprod Toxicol ; 58: 15-23, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26216787

RESUMO

Classification of substances as teratogenic is based on the observation of external, visceral and skeletal anomalies. Characterization of anomalies as variation or malformation is contingent upon their postnatal persistence and adversity to health. Lack of information thereof may result in inconsistent or incorrect classification. The aim of this work is the examination of vertebral skeletal anomalies regarding their postnatal fate on PNDs 7 and 21. The anomalies unossified, asymmetric ossification, bipartite ossification, hemicentric, as well as misshapen, did not persist up to PND21 and should be classified as a variation. The finding, cervical vertebra centrum dumbbell-shaped, should be categorized as a malformation due to its continued presence on PND 21. Lumbar centrum supernumerary sinister/dexter/sinister+dexter should also be classified as a malformation. This study demonstrates that postnatal examination is useful and substantially improves the ability to perform a scientifically sound classification of an anomaly compared to investigations terminated on GD 21.


Assuntos
Anormalidades Induzidas por Medicamentos/classificação , Anormalidades Induzidas por Medicamentos/etiologia , Floxuridina/classificação , Floxuridina/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Coluna Vertebral/anormalidades , Coluna Vertebral/efeitos dos fármacos , Teratogênicos/classificação , Teratogênicos/toxicidade , Terminologia como Assunto , Fatores Etários , Animais , Feminino , Idade Gestacional , Masculino , Gravidez , Ratos Wistar , Medição de Risco , Toxicologia/métodos
3.
Eur Cell Mater ; 26: 66-79; discussion 79, 2013 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-24027020

RESUMO

Reconstruction of critical size bone defects represents a major challenge in orthopaedic surgery. Insufficient angiogenesis is a limiting factor for engraftment of large-scale tissue transplants. Transplantation or stimulation of local mesenchymal stem cells (MSCs) represents a potential solution to enhance angiogenesis. We recently identified angiogenic properties for the Toll-like receptor (TLR) 2/6 agonist MALP-2 and now investigated if MALP-2 could be used to stimulate MSCs in order to promote angiogenesis in vitro and in vivo. Human MSCs from the bone marrow of healthy subjects were isolated, cultured and expanded in vitro and were shown to be positive for mesenchymal stem cells markers as well as for the MALP-2 receptors TLR2 and TLR6. MALP-2 directly enhanced migration but not proliferation of human MSCs. Conditioned medium from MALP-2 stimulated MSCs significantly increased proliferation, migration and tube formation of endothelial cells. Analysis of the conditioned medium from MSCs revealed that MALP-2 stimulation enhanced the secretion of several chemokines and growth factors including vascular endothelial growth factors (VEGF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Finally, we studied MALP-2 effects on MSCs in a sheep model of tissue engineering in vivo. Therefore, MSCs were isolated from the iliac crest of black head sheep and co-cultivated with MALP-2 ex vivo. Implantation of autologous MSCs within a scaffold cylinder into the M. latissimus dorsi significantly enhanced vessel density of these constructs after 6 months. We here present the first evidence that TLR2/6-dependent stimulation of MSCs promotes angiogenesis in vitro and in vivo offering a novel strategy for therapeutic angiogenesis, e.g., for tissue engineering of bone.


Assuntos
Células-Tronco Mesenquimais/fisiologia , Neovascularização Fisiológica , Comunicação Parácrina , Receptor 2 Toll-Like/metabolismo , Receptor 6 Toll-Like/metabolismo , Animais , Movimento Celular , Proliferação de Células , Quimiocinas/genética , Quimiocinas/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Lipopeptídeos/farmacologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Músculo Esquelético/fisiologia , Regeneração , Ovinos , Engenharia Tecidual , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 6 Toll-Like/antagonistas & inibidores
4.
Laryngorhinootologie ; 90(12): 747-52, 2011 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-21544750

RESUMO

BACKGROUND: Microsurgical dissection exercises are essential in otosurgery training. Human temporal bone specimens are rarely available for necessary extensive preparation steps up to the cochlea. This requires the development of new Anatomical Facsimile Models (AFM) of the temporal bone with its diffizil internal structures. MATERIAL AND METHODS: The construction of AFM was realized by rapid prototyping technologies. Data for processing come from high resolution CT-scans. RESULTS: With the production of AFM true to the original structures of the temporal bone by rapid prototyping methods it was possible to reproduce the very small cavity structures of the inner ear (cochlea, semicircular canals). All cavity structures of the temporal bone, including the middle ear, are constructed without solid support material. This allows the introduction of Cochlea-Implant electrodes into the cochlea. CONCLUSION: The use of modern rapid prototyping technologies enables us to produce any number of identical models of an original specimen. The preparation steps and the material properties correspond to those of the original temporal bone. Therefore AFM are excellent preparation models.


Assuntos
Simulação por Computador , Orelha Interna/anatomia & histologia , Orelha Interna/cirurgia , Orelha Média/anatomia & histologia , Orelha Média/cirurgia , Microcirurgia/educação , Modelos Anatômicos , Otolaringologia/educação , Osso Temporal/anatomia & histologia , Implante Coclear/educação , Desenho Assistido por Computador , Currículo , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , Software , Tomografia Computadorizada por Raios X/métodos
5.
Reprod Toxicol ; 31(4): 574-84, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21338671

RESUMO

There is growing concern that environmental substances with a potential to modulate the hormonal system may have harmful effects on human health. Consequently, a new EU regulation names endocrine disrupting properties as one of the cut-off criteria for the approval of plant protection products, although it currently fails to provide specific science-based measures for the assessment of substances with such properties. Since specific measures are to be presented by the European Commission in 2013 the development of assessment and decision criteria is a key challenge concerning the implementation of this new EU regulation. Proposals of such decision criteria for substances with potential endocrine disrupting properties in human health risk assessment were developed by the German Federal Institute for Risk Assessment (BfR) and discussed at an expert workshop in November 2009. Under consideration of the requirements laid down within the new plant protection product legislation and the scientific discussions during the workshop, a conceptual framework on evaluation of substances for endocrine disrupting properties in a regulatory context is presented in this paper. Central aspects of the framework include assessment of adversity of effects, establishment of a mode/mechanism of action in animals, considerations concerning the relevance of effects to humans and two options for a regulatory decision.


Assuntos
Disruptores Endócrinos/toxicidade , Monitoramento Ambiental , Praguicidas/toxicidade , Testes de Toxicidade , Animais , Mineração de Dados , Bases de Dados Factuais , Técnicas de Apoio para a Decisão , Monitoramento Ambiental/legislação & jurisprudência , Monitoramento Ambiental/normas , Europa (Continente) , Guias como Assunto , Humanos , Medição de Risco , Testes de Toxicidade/normas
6.
Exp Toxicol Pathol ; 60(4-5): 313-21, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18513932

RESUMO

Triphenyltin is an organotin compound that has been used extensively as an antifouling biocide and as an agricultural pesticide. Certain organotin compounds act as endocrine-active agents and have been reported to affect reproduction in mollusks and mammals. Here we studied the histopathological effects of 2 or 6mg triphenyltin chloride (TPTCl)/kg b.w. on the reproductive tissue and the thymus of female pubertal rats as part of a comprehensive pubertal assay. Beginning at postnatal day (PND) 23 female Wistar rats were treated daily per gavage until their first estrus after PND 53. Reproductive organs were removed and histologically evaluated. While no histological changes were observed in oviduct, uterus, vagina and mamma, an increase in the number of all follicle stages occurred at both dose levels. Furthermore, exposure to 2mg TPTCl/kg b.w. led to a significant reduction in the diameter of tertiary follicles. A significant increase in the number of atretic follicles was observed in tertiary and preovulatory follicles after exposure to 6mg TPTCl. The thymus displayed a decreased number of apoptotic cells in both dose groups. We conclude that peripubertal administration of 2 and 6mg TPTCl/kg b.w. caused effects on ovarian follicles of female rats.


Assuntos
Anti-Infecciosos/toxicidade , Compostos Orgânicos de Estanho/toxicidade , Ovário/efeitos dos fármacos , Ovário/patologia , Animais , Feminino , Imuno-Histoquímica , Ratos , Ratos Wistar , Timo/efeitos dos fármacos , Timo/patologia
7.
Mol Cell Endocrinol ; 248(1-2): 242-5, 2006 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-16406283

RESUMO

In this study, we developed an automated in silico Northern blot (ISNB) for analysis of gene expression patterns from EST databases. This kind of analysis can facilitate initial enzyme characterization by providing tissue distribution patterns. For proof of principle, we analyzed the expression pattern of well-characterized murine 17beta-hydroxysteroid dehydrogenases type 1 and 4. Less characterized murine 17beta-hydroxysteroid dehydrogenase type 11 (Dhrs 8) also was included and processed bioinformatically (ISNB) and further analyzed by Northern blot. The 17beta-hydroxysteroid dehydrogenase type 11 showed the same wide expression pattern by in silico and by wet laboratory approaches. The data point to its involvement of the enzyme in lipid metabolism. The quality of the ISNB relies on the quality of EST-databases. However, our approach is an easy and versatile tool of potentially universal application.


Assuntos
17-Hidroxiesteroide Desidrogenases/genética , Northern Blotting , Biologia Computacional/métodos , Bases de Dados Genéticas , Etiquetas de Sequências Expressas , Animais , Expressão Gênica , Camundongos , Distribuição Tecidual/genética
8.
Environ Res ; 101(1): 81-8, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16162336

RESUMO

In a one-generation reproductive study, the fungicidal compound triphenyltin hydroxide (fentin) was administered to adult Japanese quail for 6 weeks at dietary levels of 3 and 30 ppm. Reproduction was significantly impaired in the high-dose group. The principal adverse finding was a marked increase in embryonic mortality, resulting in a lower hatch rate. Furthermore, a reduction in egg production was observed with ongoing duration of treatment. Most of the other reproduction-related parameters were not affected. The in ovo losses are assumed to result from a direct toxic effect of the test substance on chick embryos. At the low dietary level, reproduction was not altered. In contrast to the obvious reproductive toxicity, there was only limited evidence of adverse treatment-related findings in the adult birds. However, because such minor effects as an increase in mean liver weight, which was accompanied by macroscopic liver findings and a decrease in T4 serum concentration, were still seen at 3 ppm, a no-observed-effect level could not be established.


Assuntos
Coturnix/fisiologia , Compostos Orgânicos de Estanho/toxicidade , Reprodução/efeitos dos fármacos , Animais , Casca de Ovo/efeitos dos fármacos , Estradiol/sangue , Feminino , Masculino , Nível de Efeito Adverso não Observado , Testosterona/sangue , Tiroxina/sangue
9.
Bioinformatics ; 21(13): 2933-42, 2005 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-15860560

RESUMO

MOTIVATION: Promoter analysis is an essential step on the way to identify regulatory networks. A prerequisite for successful promoter analysis is the prediction of potential transcription factor binding sites (TFBS) with reasonable accuracy. The next steps in promoter analysis can be tackled only with reliable predictions, e.g. finding phylogenetically conserved patterns or identifying higher order combinations of sites in promoters of co-regulated genes. RESULTS: We present a new version of the program MatInspector that identifies TFBS in nucleotide sequences using a large library of weight matrices. By introducing a matrix family concept, optimized thresholds, and comparative analysis, the enhanced program produces concise results avoiding redundant and false-positive matches. We describe a number of programs based on MatInspector allowing in-depth promoter analysis (DiAlignTF, FrameWorker) and targeted design of regulatory sequences (SequenceShaper).


Assuntos
Algoritmos , Regiões Promotoras Genéticas/genética , Alinhamento de Sequência/métodos , Análise de Sequência de DNA/métodos , Fatores de Transcrição/genética , Transcrição Gênica/genética , Sequência de Bases , Sítios de Ligação , Sequência Conservada , Dados de Sequência Molecular , Ligação Proteica , Homologia de Sequência do Ácido Nucleico , Software
10.
Bioinformatics ; 20(2): 268-70, 2004 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-14734319

RESUMO

SUMMARY: The Helmholtz Network for Bioinformatics (HNB) is a joint venture of eleven German bioinformatics research groups that offers convenient access to numerous bioinformatics resources through a single web portal. The 'Guided Solution Finder' which is available through the HNB portal helps users to locate the appropriate resources to answer their queries by employing a detailed, tree-like questionnaire. Furthermore, automated complex tool cascades ('tasks'), involving resources located on different servers, have been implemented, allowing users to perform comprehensive data analyses without the requirement of further manual intervention for data transfer and re-formatting. Currently, automated cascades for the analysis of regulatory DNA segments as well as for the prediction of protein functional properties are provided. AVAILABILITY: The HNB portal is available at http://www.hnbioinfo.de


Assuntos
Algoritmos , Biologia Computacional/métodos , Sistemas de Gerenciamento de Base de Dados , Armazenamento e Recuperação da Informação/métodos , Internet , Análise de Sequência de DNA/métodos , Análise de Sequência de Proteína/métodos , Interface Usuário-Computador , Biologia Computacional/organização & administração , Alemanha , Relações Interinstitucionais , Software
11.
Psychopharmacology (Berl) ; 157(4): 340-8, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11605092

RESUMO

RATIONALE: Acute serotonin (5-HT) depletion by the tryptophan hydroxylase inhibitor, para-chlorophenylalanine, attenuates cocaine seeking in rats. OBJECTIVE: The present study examined the effects of chronic 5-HT depletion on cocaine- and sucrose seeking using the 5-HT-selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). METHODS: Separate groups of rats were trained to lever press for cocaine infusions (0.33 mg/kg/0.1 ml, i.v.) or for sucrose pellets (45 mg Noyes) on a fixed ratio (FR) 1 schedule of reinforcement during daily 2-h sessions. Subsequently, animals received i.c.v. infusions of either vehicle or 5,7-DHT (150 microg/6 microl or 200 microg/20 microl). After a minimum of 10 days post-lesion, cocaine- and sucrose seeking were measured as lever presses in the absence of reinforcement (extinction). Some cocaine-trained animals were also assessed for the re-establishment of self-administration and reinstatement of extinguished cocaine seeking by i.v. cocaine priming injections and response-contingent presentations of cocaine-paired stimuli. RESULTS: 5-HT depletion by the 150 microg/6 microl dose of 5,7-DHT failed to alter cocaine- and sucrose seeking despite producing a 42-77% depletion of 5-HT in limbic terminal regions. The 200 microg/20 microl dose of 5,7-DHT attenuated cocaine seeking but enhanced sucrose seeking during extinction and produced a 55-85% depletion of 5-HT. In addition, cocaine-paired cues and cocaine priming reinstated cocaine-seeking behavior, and responding was enhanced in 5,7-DHT-treated animals relative to vehicle-treated controls at the 1 mg/kg/0.1 ml priming dose. However, re-establishment of cocaine self-administration was not altered by 5,7-DHT. CONCLUSION: The results suggest that 5-HT depletion may attenuate cocaine seeking but may enhance sucrose seeking when animals are tested during extinction. Furthermore, 5-HT depletion may enhance cocaine seeking produced by cocaine itself. Together these findings suggest that 5-HT depletion may have opposite effects on incentive motivation for cocaine during abstinence versus relapse.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Serotonina/fisiologia , Paladar/efeitos dos fármacos , 5,7-Di-Hidroxitriptamina/farmacologia , Animais , Condicionamento Operante/efeitos dos fármacos , Extinção Psicológica , Injeções Intravenosas , Masculino , Ratos , Ratos Sprague-Dawley , Autoadministração , Serotoninérgicos/farmacologia , Sacarose
12.
J Neurol ; 248(5): 410-5, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11437164

RESUMO

Charcot-Marie-Tooth disease type 1 (CMT1) is a demyelinating peripheral neuropathy most commonly caused by a DNA duplication on chromosome 17p11.2 including the peripheral myelin protein 22 (PMP22). Point mutations in the myelin protein zero gene (MPZ) and gap junction protein, beta-1 gene (GJB1) are also found in association with CMT1 or the subclass of CMT type X (CMTX), respectively. Recently point mutations in these genes have been found in patients showing the axonal variant of CMT, CMT type 2 (CMT2). We here describe the clinical and electro-physiological findings caused by two novel and two recently described MPZ mutations and six GJB1 mutations. Different MPZ and GJB1 mutations were associated with different grades of severity in CMT1 and CMTX. The novel MPZ Glu141st op mutation was associated with the axonal CMT2. We conclude that the clinical and electrophysiological heterogeneity among CMT patients carrying point mutations in MPZ and GJB1 is similar. Thus for clinical purposes CMT1 and CMT2 patients should be screened for mutations in these two genes after duplication on chromosome 17p11.2 has been excluded as the disease causing mutation.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Cromossomos Humanos Par 17/genética , Conexinas/genética , Proteína P0 da Mielina/genética , Mutação Puntual , Adolescente , Adulto , Doença de Charcot-Marie-Tooth/patologia , Criança , Eletrofisiologia , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Índice de Gravidade de Doença
13.
Genome Res ; 11(3): 333-40, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11230158

RESUMO

The publication of the first almost complete sequence of a human chromosome (chromosome 22) is a major milestone in human genomics. Together with the sequence, an excellent annotation of genes was published which certainly will serve as an information resource for numerous future projects. We noted that the annotation did not cover regulatory regions; in particular, no promoter annotation has been provided. Here we present an analysis of the complete published chromosome 22 sequence for promoters. A recent breakthrough in specific in silico prediction of promoter regions enabled us to attempt large-scale prediction of promoter regions on chromosome 22. Scanning of sequence databases revealed only 20 experimentally verified promoters, of which 10 were correctly predicted by our approach. Nearly 40% of our 465 predicted promoter regions are supported by the currently available gene annotation. Promoter finding also provides a biologically meaningful method for "chromosomal scaffolding", by which long genomic sequences can be divided into segments starting with a gene. As one example, the combination of promoter region prediction with exon/intron structure predictions greatly enhances the specificity of de novo gene finding. The present study demonstrates that it is possible to identify promoters in silico on the chromosomal level with sufficient reliability for experimental planning and indicates that a wealth of information about regulatory regions can be extracted from current large-scale (megabase) sequencing projects. Results are available on-line at http://genomatix.gsf.de/chr22/.


Assuntos
Cromossomos Humanos Par 22/genética , Biologia Computacional , Projeto Genoma Humano , Regiões Promotoras Genéticas/genética , Análise de Sequência de DNA , Algoritmos , Biologia Computacional/métodos , Biologia Computacional/tendências , Previsões , Humanos , Reprodutibilidade dos Testes , Análise de Sequência de DNA/tendências , Validação de Programas de Computador
14.
J Immunol ; 164(2): 554-7, 2000 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-10623793

RESUMO

Mycoplasmas and their membranes are potent activators of macrophages, the active principle being lipoproteins and lipopeptides. Two stereoisomers of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 (MALP-2) differing in the configuration of the lipid moiety were synthesized and compared in their macrophage-activating potential, the R-MALP being >100 times more active than the S-MALP in stimulating the release of cytokines, chemokines, and NO. To assess the role of the Toll-like receptor (TLR) family in mycoplasmal lipopeptide signaling, the MALP-2-mediated responses were analyzed using macrophages from wild-type, TLR2-, TLR4-, and MyD88-deficient mice. TLR2- and MyD88-deficient cells showed severely impaired cytokine productions in response to R- and S-MALP. The MALP-induced activation of intracellular signaling molecules was fully dependent on both TLR2 and MyD88. There was a strong preference for the R-MALP in the recognition by its functional receptor, TLR2.


Assuntos
Antígenos de Diferenciação/fisiologia , Proteínas de Drosophila , Lipoproteínas/fisiologia , Ativação de Macrófagos/imunologia , Glicoproteínas de Membrana/fisiologia , Mycoplasma fermentans/imunologia , Oligopeptídeos/fisiologia , Receptores de Superfície Celular/fisiologia , Receptores Imunológicos , Transdução de Sinais/imunologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Antígenos de Diferenciação/genética , Células Cultivadas , Lipopeptídeos , Lipoproteínas/química , Ativação de Macrófagos/genética , Macrófagos Peritoneais/imunologia , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide , Oligopeptídeos/química , Receptores de Superfície Celular/genética , Transdução de Sinais/genética , Estereoisomerismo , Relação Estrutura-Atividade , Receptor 2 Toll-Like , Receptor 4 Toll-Like , Receptores Toll-Like
15.
Psychopharmacology (Berl) ; 146(1): 60-6, 1999 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-10485965

RESUMO

RATIONALE: Alterations in serotonin (5-HT) neurotransmission during cocaine withdrawal may be involved in incentive motivation for cocaine. OBJECTIVE: The present study examined the effects of 5-HT depletion on cocaine- and food-seeking behavior (i.e., non-reinforced operant responding). METHODS: Separate groups of rats were trained to lever press for cocaine infusions (0.33 mg/kg/0.1 ml, i.v.) or for food pellets (45-mg Noyes food pellets) on a fixed-ratio one schedule of reinforcement during 14 daily 2-h sessions. Half of each group then received treatment with either saline or the tryptophan hydroxylase inhibitor para-chlorophenylalanine (p-CPA; 100 mg/kg, i.p.) on post-training day 5 and day 6. Twenty-four hours after their last treatment, rats were tested for cocaine- or food-seeking behavior by measuring operant responding in the absence of reinforcement until they reached an extinction criterion of no responses for 30 min. Animals were sacrificed 24 h after testing and brain 5-HT levels in various regions were quantified. RESULTS: In cocaine-trained animals, p-CPA treatment significantly decreased cocaine-seeking behavior and produced a trend toward a decrease in extinction latency relative to saline treatment. In food-trained animals, p-CPA treatment failed to alter any of the behavioral measures during testing, suggesting that p-CPA treatment did not alter the animals' memory or ability to perform an operant response. p-CPA significantly depleted 5-HT by 73-85% in every brain region examined. CONCLUSION: The results suggest that decreasing 5-HT neurotransmission may decrease incentive motivation for cocaine.


Assuntos
Cocaína/administração & dosagem , Serotonina/fisiologia , Animais , Química Encefálica/efeitos dos fármacos , Ingestão de Alimentos , Extinção Psicológica , Masculino , Motivação , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Tempo de Reação , Autoadministração , Serotonina/análise
16.
Plant J ; 18(5): 565-70, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10417707

RESUMO

A new aquaporin from Nicotiana tabacum (cv. Samsun) was characterized. It shares sequence homology to the Arabidopsis thaliana PIP1 protein family. By two-phase partitioning and immunoblot analysis, plasma membrane localization could be demonstrated. The corresponding mRNA is highly abundant in roots and flowers, while it is rarely expressed in leaves and stems. Functional expression in Xenopus oocytes revealed that NtAQP1 can mediate glycerol transport in addition to water flow. However, NtAQP1 is impermeable for Na+, K+ and Cl- ions. The water permeability and selectivity could not be modulated by addition of mercurials or the activity of cAMP-dependent protein kinases.


Assuntos
Aquaporinas/genética , Glicerol/metabolismo , Nicotiana/genética , Proteínas de Plantas/genética , Plantas Tóxicas , Água/metabolismo , Animais , Aquaporina 1 , Aquaporinas/efeitos dos fármacos , Aquaporinas/metabolismo , Transporte Biológico , Permeabilidade da Membrana Celular , DNA Complementar/genética , Condutividade Elétrica , Feminino , Biblioteca Gênica , Mercúrio/farmacologia , Dados de Sequência Molecular , Oócitos , Pressão Osmótica , Proteínas de Plantas/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Análise de Sequência de DNA , Distribuição Tecidual , Xenopus
17.
Plant J ; 14(1): 121-8, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9681029

RESUMO

The plant plasma membrane intrinsic protein, PIP1b, facilitates water transport. These features were characterized in Xenopus oocytes and it has asked whether aquaporins are relevant for water transport in plants. In order to elucidate this uncertainty Arabidopsis thaliana was transformed with an anti-sense construct targeted to the PIP1b gene. Molecular analysis revealed that the anti-sense lines have reduced steady-state levels of PIP1b and the highly homologous PIP1a mRNA. The cell membrane water permeability was analyzed by swelling of protoplasts, which had been transferred into hypotonic conditions. The results indicate that the reduced expression of the specific aquaporins decreases the cellular osmotic water permeability coefficient approximately three times. The morphology and development of the anti-sense lines resembles that of control plants, with the exception of the root system, which is five times as abundant as that of control plants. Xylem pressure measurement suggests that the increase of root mass compensates the reduced cellular water permeability in order to ensure a sufficient water supply to the plant. The results obtained by this study, therefore, clearly demonstrate that aquaporins are important for plant water transport.


Assuntos
Arabidopsis/metabolismo , Canais Iônicos/metabolismo , Água/metabolismo , Animais , Arabidopsis/genética , Transporte Biológico Ativo , Membrana Celular/metabolismo , DNA Antissenso/genética , Feminino , Canais Iônicos/genética , Osmose , Permeabilidade , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transformação Genética
18.
Chemosphere ; 34(5-7): 1523-34, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9134684

RESUMO

The tissue distribution and toxicokinetics of PCB-77 after a single s.c. dose of 6 mg/kg body weight was investigated in male adult rats as well as the concurrent induction of hepatic drug-metabolizing enzymes. During five days after treatment, the PCB-77 concentrations on fat weight basis in testis and in whole blood were found to be about in the same range as the concentrations in adipose tissue, whereas in liver fat PCB-77 accumulated. EROD and MROD activities were induced by about 8 and 4 times, respectively, during a period of two weeks after treatment. Concentrations in adipose tissue and in liver as well as the hepatic enzyme activities rapidly declined during the investigation period of eight weeks. An elimination half-life for PCB-77 of approximately 7-9 days was estimated.


Assuntos
Citocromo P-450 CYP1A1/biossíntese , Sistema Enzimático do Citocromo P-450/biossíntese , Fígado/efeitos dos fármacos , Oxirredutases/biossíntese , Bifenilos Policlorados/farmacocinética , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/enzimologia , Animais , Indução Enzimática , Injeções Subcutâneas , Fígado/enzimologia , Masculino , Bifenilos Policlorados/sangue , Ratos , Ratos Wistar , Testículo/efeitos dos fármacos , Testículo/enzimologia , Distribuição Tecidual
19.
Retina ; 17(3): 179-85, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9196926

RESUMO

PURPOSE: To investigate whether postoperative face-down positioning is necessary for successful macular hole repair. BACKGROUND: Although never proven, face-down positioning is strongly considered an important maneuver to achieve macular hole closure. Face-down posturing is inconvenient, and for patients with physical or mental limitations, weeks of face-down positioning may be an impossible task. A gas bubble that completely fills the vitreous cavity will tamponade a macular hole despite head position and may close a macular hole as effectively as a partial gas fill with face-down positioning. If face-down positioning were not necessary, more patients would be eligible to benefit from this surgery. METHODS: Thirty-three consecutive eyes in 31 patients aged 65-79 years with Stage II, III, or IV full-thickness macular holes underwent macular hole surgery with a complete 15% C3F8 vitreous fill. Hole duration varied from 1 month to 10 years; in 21% of eyes, (seven of 33) holes had been present for more than 1 year. All phakic eyes (n = 25) had cataract extraction with intraocular lens insertion when macular hole surgery was done. No patients were positioned face down. RESULTS: The follow-up period was 6-40 months; 73% of the patients have been observed for more than 1 year. Preoperative hole duration did not affect hole closure rate. The success rate after one surgery was 79% (26 of 33 eyes), and with additional vitrectomy surgery, the total success rate was 85% (28 of 33 eyes). Forty-eight percent of eyes attained visual acuity of 20/50. Eighty percent of eyes with preoperative acuity of > 20/100 attained > 20/50 acuity. Significant complications included iris incarceration into the cataract wound during a postoperative fluid-gas exchange (one eye), posterior synechiae (four eyes), intraocular lens capture (two eyes), elevated intraocular pressure (three eyes), and retinal detachment (three eyes). Most of these problems can be avoided or reduced. CONCLUSION: This pilot study suggests that successful macular hole closure is possible without face-down positioning. This technique may be an alternative for patients with macular holes in pseudophakic eyes who are unable to assume face-down posturing. Combining cataract surgery with this technique for macular hole repair is reasonable for phakic patients who cannot maintain prone positioning. Major disadvantages of combined surgery include the morbidity of the second procedure and removal of a visually insignificant cataract. This approach should be considered for those patients unable to tolerate face-down positioning.


Assuntos
Postura , Perfurações Retinianas/cirurgia , Vitrectomia/métodos , Catarata/complicações , Face , Fluorocarbonos/administração & dosagem , Seguimentos , Humanos , Pressão Intraocular , Lentes Intraoculares , Fotocoagulação , Macula Lutea/patologia , Pessoa de Meia-Idade , Facoemulsificação , Projetos Piloto , Complicações Pós-Operatórias , Perfurações Retinianas/complicações , Acuidade Visual , Vitrectomia/efeitos adversos
20.
Comput Appl Biosci ; 12(5): 405-13, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8996789

RESUMO

MOTIVATION: Most of the sequences determined in current genome sequencing projects remain at least partially unannotated. The available software for DNA sequence analysis is usually limited to the prediction of individual elements (level 1 methods), but does not assess the context of different motifs. However, the functionality of biological units like promoters depends on the correct spatial organization of multiple individual elements. RESULTS: Here, we present a second-level software package called GenomeInspector [[http:@www.gsf.de/biodv/genomeinspector.html ]], for further analysis of results obtained with level 1 methods (e.g. MatInspector [[http:@www.gsf.de/biodv/matinspector.html ]] or ConsInspector [[http:@www.gsf.de/biodv/consinspector.html++ +]]). One of the main features of this modular program is its ability to assess distance correlations between large sets of sequence elements which can be used for the identification and definition of basic patterns of functional units. The program provides an easy-to-use graphical user interface with direct comprehensive display of all results for megabase sequences. Sequence elements showing spatial correlations can be easily extracted and traced back to the nucleotide sequence with the program. GenomeInspector identified promoters of glycolytic enzymes in yeast [[http:@www.mips.biochem.mpg.de/mips/yeast/]] as members of a subgroup with unusual location of an ABF1 site. Solely on the basis of distance correlation analysis, the program correctly selected those transcription factors within these promoters already known to be involved in the regulation of glycolytic enzymes, demonstrating the power of this method.


Assuntos
DNA/análise , Análise de Sequência , Software , Algoritmos , Sequência de Bases , Sítios de Ligação , Gráficos por Computador , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Saccharomyces cerevisiae/genética , Fatores de Transcrição/análise , Interface Usuário-Computador
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