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1.
Opt Express ; 23(3): 2472-86, 2015 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-25836115

RESUMO

The performance of a 665-nm GaInP disk laser operated continuous-wave at 15°C both in-well-pumped at 640 nm and barrier pumped at 532 nm is reported. The efficiency with respect to the absorbed power was enhanced by 3.5 times when using a 640-nm pump instead of a 532-nm pump. In-well pumping which is based on the absorption of the pump photons within the quantum-well heterostructures of the gain region instead of short-wavelength absorption in the barrier and spacer regions reduces the quantum defect between pump and laser photon and hence the heat generation. A slope efficiency of 60% with respect to the absorbed pump power was obtained by in-well pumping at 15°C. Continuous-wave laser operation was further demonstrated at heat sink temperatures of up to 55°C. Both the measurement of photoluminescence and COMSOL simulation show that the overall heat load in the in-well pumped laser is smaller than in the barrier-pumped laser. These results demonstrate the potential of optical in-well pumping for the operation of red AlGaInP disk lasers if combined with means for efficient pump-light absorption.

2.
Opt Lett ; 40(7): 1532-5, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25831377

RESUMO

We report for the first time, to the best of our knowledge, an innovative design concept for intracavity pulse stretching in a regenerative amplifier, employing a single "grating-mirror" based on a leaky-mode grating-waveguide design. The very compact and flexible layout allows for femtosecond pulses to be in principle easily stretched up to nanosecond durations. The design has been tested in a diode-pumped Yb:CALGO regenerative amplifier followed by a standard transmission grating compressor. Sub-200-fs pulses (stretched pulses ≈110 ps) with 205-µJ energy at 20-kHz repetition rate have been demonstrated. In order to prove the robustness and potential for energy scaling of leaky-mode grating-waveguide intracavity stretcher, we generated stretched pulses with energies of up to ≈700 µJ (400-ps long) at a lower repetition rate of 10 kHz. A simple model is proposed for the study of the cavity in presence of induced spatial chirp.

3.
Herz ; 40(2): 224-30, 2015 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-25737288

RESUMO

Treatment of patients in cardiogenic shock (CS) presenting with acute myocardial infarction (AMI) is still a challenge and mortality rates remain high, approaching 50 %. Hemodynamic stabilization before and/or after early revascularization remains the primary goal in these patients. In addition to hemodynamic support by inotropes and vasopressors, support with mechanical devices such as intra-aortic balloon pumping (IABP), percutaneous left ventricular assist devices (LVAD) and complete extracorporeal life support (ECLS) with extracorporeal membrane oxygenation (ECMO) may be considered. The use of IABP cannot be recommended anymore on a routine basis. Unfortunately, there are no large randomized data from studies evaluating treatment with mechanical support systems compared to standard treatment with respect to the clinical outcome of patients and no head-to-head comparison of different devices is available. Another important open question to be answered is which subgroups of patients may have a benefit from LVAD therapy. Guidelines discourage the routine use of mechanical support as a first-line treatment in CS patients and emphasize that the application should be restricted to those patients with refractory shock. This article gives an overview of the different devices for percutaneous mechanical support in CS and describes the available evidence and guideline recommendations.


Assuntos
Oxigenação por Membrana Extracorpórea/instrumentação , Coração Auxiliar , Balão Intra-Aórtico/instrumentação , Choque Cardiogênico/terapia , Terapia Combinada/instrumentação , Análise de Falha de Equipamento , Medicina Baseada em Evidências , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Balão Intra-Aórtico/métodos , Desenho de Prótese , Choque Cardiogênico/diagnóstico , Resultado do Tratamento
4.
Gesundheitswesen ; 77 Suppl 1: S95-6, 2015 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-23970389

RESUMO

The effect of health promotion at the worksite for overweight adolescents is not known. This 2-year intervention study examined the effect of a multimodal programme including nutrition counselling, sport, and life-skill training on medical and psychological outcomes. The body mass index increased slightly less in the intervention group. Semistructured interviews at the end showed that participants are highly interested in health promotion at the worksite.


Assuntos
Dietoterapia/estatística & dados numéricos , Ocupações em Saúde/estatística & dados numéricos , Promoção da Saúde/estatística & dados numéricos , Sobrepeso/epidemiologia , Sobrepeso/prevenção & controle , Participação do Paciente/estatística & dados numéricos , Adolescente , Terapia Combinada , Terapia por Exercício/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Prevalência , Esportes , Resultado do Tratamento , Programas de Redução de Peso , Local de Trabalho , Adulto Jovem
5.
Opt Lett ; 37(19): 3984-6, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23027253

RESUMO

A mode-locked thin-disk laser based on Yb:CALGO is demonstrated for the first time. At an average output power of 28 W we obtained pulses with a duration of 300 fs and a pulse energy of 1.3 µJ. 197 fs pulses with 0.9 µJ of energy were achieved at an average output power of 20 W. The shortest pulse duration measured in our experiments was 135 fs with a spectrum centered at 1043 nm. The experiments also revealed a very broad tunability from 1032 to 1046 nm with sub-200 fs pulses.

6.
J Opt Soc Am A Opt Image Sci Vis ; 29(9): 1860-9, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23201942

RESUMO

We investigate the linear propagation of Gaussian-apodized solutions to the paraxial wave equation in free-space and first-order optical systems. In particular, we present complex coordinate transformations that yield a very general and efficient method to apply a Gaussian apodization (possibly with initial phase curvature) to a solution of the paraxial wave equation. Moreover, we show how this method can be extended from free space to describe propagation behavior through nonimaging first-order optical systems by combining our coordinate transform approach with ray transfer matrix methods. Our framework includes several classes of interesting beams that are important in applications as special cases. Among these are, for example, the Bessel-Gauss and the Airy-Gauss beams, which are of strong interest to researchers and practitioners in various fields.

7.
Transfus Med ; 22(1): 57-62, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22132772

RESUMO

OBJECTIVES: The aim of this work is to provide the first report of a transfusion-acquired HIV-1 infection and to verify transmission from the donor to the recipients using phylogenetic analysis of HIV-1 DNA sequences in a Brazilian blood bank. BACKGROUND: Although haemovigilance procedures based on phylogenetic analysis of HIV have been reported in several countries, this type of study has yet to be conducted in Latin America. MATERIALS AND METHODS: Upon identifying a HIV-1-positive repeat blood donor by enzyme immunoassay (EIA) blood screening, all recipients of the donor's previous donation were identified and tested for HIV-1 by EIA, nucleic acid amplification test and HIV-1 DNA sequencing and phylogenetic analysis. RESULTS: One of the recipients tested positive for HIV-1. The phylogenetic analysis showed a high genetic similarity among the viruses, thus supporting the hypothesis of transmission from the donor to the recipient. CONCLUSIONS: Phylogenetic analysis of HIV-1 DNA sequences has been a decisive tool in verifying suspected transmission of the virus from blood donor to recipient in Brazil.


Assuntos
Bancos de Sangue , Doadores de Sangue , Segurança do Sangue , Transfusão de Sangue , Patógenos Transmitidos pelo Sangue , DNA Viral/genética , Infecções por HIV , HIV-1/genética , Filogenia , Adulto , Brasil , Feminino , Infecções por HIV/genética , Infecções por HIV/transmissão , Humanos
8.
Herz ; 37(2): 191-7; quiz 198-9, 2012 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-22430321

RESUMO

Arterial hypertension is the most important risk factor for coronary artery disease (CAD). There is a high coincidence of both diseases, whereby both impair coronary microcirculatory function synergistically, which can be measured functionally by decreased coronary flow reserve. This dysfunction leads to permanent damage to the left ventricular myocardium. Lifestyle changes play a central role in the primary and secondary prevention of CAD. Additionally, there are well-established options for antihypertensive drug therapy, which should be combined with aspirin and statins. Pharmacological treatment should follow distinctive blood pressure goals in relation to the severity of CAD. Particular attention is paid in this context to the relation between diastolic blood pressure values and cardiovascular endpoints, which displays a j-shaped curve with the lowest risk at levels between 70 and 90 mmHg.


Assuntos
Anticoagulantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Doença da Artéria Coronariana/diagnóstico , Quimioterapia Combinada , Humanos , Hipertensão/diagnóstico
9.
Opt Lett ; 36(21): 4134-6, 2011 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22048342

RESUMO

We present the first demonstration of a Yb:CALGO thin-disk laser. In a slightly multimode configuration, we obtained up to 30 W of average power at a slope efficiency of 40% and an optical-to-optical efficiency of 32%. With a single-mode cavity, an average power of 25 W was achieved. A tuning range from 1018 to 1052 nm could be demonstrated by inserting a prism into the cavity. In the Q-switched regime, we obtained 1 mJ of pulse energy at a repetition rate of 100 Hz.

10.
Br J Anaesth ; 107(2): 243-50, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21652615

RESUMO

BACKGROUND: The single-use supraglottic airway device i-gel™ has been described in several case reports as a conduit for intubation, but no prospective data about success rates of blind intubation are available. Therefore, we performed this prospective randomized controlled trial to compare the success rate of blind tracheal intubation with a Magill PVC tube through the i-gel™ with intubation using an sILMA™ PVC tube through the single-use intubating laryngeal mask airway (sILMA™). METHODS: With ethics committee approval and written informed consent, 80 patients with predictors of a difficult airway were computer randomized to either supraglottic airway device (SAD). The corresponding tracheal tube (TT) was introduced through the SAD under fibreoptic visualization but without fibreoptic guidance. Primary outcome was blind intubation success rate. Times, airway leak pressure, fibreoptic view, and adverse events were recorded. To control for the influence of the TT, we compared data from 40 patients described in an accompanying study (sILMA™ with Magill TT and i-gel™ with sILMA™ TT). RESULTS: Blind intubation success rate through the sILMA™ (69%) was higher than with the i-gel™ (15%, P<0.001). Data from the other patient group excluded the TT type as the primary cause for the difference in success rate. Removal of SADs was without problems with no difference between the type of SAD. CONCLUSIONS: Blind tracheal intubation using the sILMA™ tube through the sILMA™ is much more successful than blind intubation with a Magill PVC tube through the i-gel™. Because of its low success rate, we would not recommend blind intubation through the i-gel™.


Assuntos
Intubação Intratraqueal/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/métodos , Remoção de Dispositivo , Equipamentos Descartáveis , Desenho de Equipamento , Feminino , Tecnologia de Fibra Óptica/métodos , Hemodinâmica , Humanos , Intubação Intratraqueal/efeitos adversos , Máscaras Laríngeas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Faringite/etiologia , Complicações Pós-Operatórias , Estudos Prospectivos , Adulto Jovem
11.
J Exp Med ; 194(1): 13-27, 2001 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-11435469

RESUMO

Podocalyxin is a CD34-related sialomucin that is expressed at high levels by podocytes, and also by mesothelial cells, vascular endothelia, platelets, and hematopoietic stem cells. To elucidate the function of podocalyxin, we generated podocalyxin-deficient (podxl(-/)-) mice by homologous recombination. Null mice exhibit profound defects in kidney development and die within 24 hours of birth with anuric renal failure. Although podocytes are present in the glomeruli of the podxl(-/)- mice, they fail to form foot processes and slit diaphragms and instead exhibit cell--cell junctional complexes (tight and adherens junctions). The corresponding reduction in permeable, glomerular filtration surface area presumably leads to the observed block in urine production. In addition, podxl(-/)- mice frequently display herniation of the gut (omphalocele), suggesting that podocalyxin may be required for retraction of the gut from the umbilical cord during development. Hematopoietic and vascular endothelial cells develop normally in the podocalyxin-deficient mice, possibly through functional compensation by other sialomucins (such as CD34). Our results provide the first example of an essential role for a sialomucin in development and suggest that defects in podocalyxin could play a role in podocyte dysfunction in renal failure and omphalocele in humans.


Assuntos
Anuria/genética , Morte Fetal/genética , Hérnia Umbilical/genética , Sialoglicoproteínas/genética , Animais , Antígenos CD34/metabolismo , Vasos Sanguíneos/embriologia , Vasos Sanguíneos/metabolismo , Diafragma/anormalidades , Edema/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Sistema Hematopoético/embriologia , Sistema Hematopoético/metabolismo , Rim/anormalidades , Rim/patologia , Masculino , Camundongos , Camundongos Mutantes , Insuficiência Renal/genética , Sialoglicoproteínas/metabolismo
12.
Sci Rep ; 10(1): 19158, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154449

RESUMO

The safety and efficacy of kratom (Mitragyna speciosa) for treatment of pain is highly controversial. Kratom produces more than 40 structurally related alkaloids, but most studies have focused on just two of these, mitragynine and 7-hydroxymitragynine. Here, we profiled 53 commercial kratom products using untargeted LC-MS metabolomics, revealing two distinct chemotypes that contain different levels of the alkaloid speciofoline. Both chemotypes were confirmed with DNA barcoding to be M. speciosa. To evaluate the biological relevance of variable speciofoline levels in kratom, we compared the opioid receptor binding activity of speciofoline, mitragynine, and 7-hydroxymitragynine. Mitragynine and 7-hydroxymitragynine function as partial agonists of the human µ-opioid receptor, while speciofoline does not exhibit measurable binding affinity at the µ-, δ- or ƙ-opioid receptors. Importantly, mitragynine and 7-hydroxymitragynine demonstrate functional selectivity for G-protein signaling, with no measurable recruitment of ß-arrestin. Overall, the study demonstrates the unique binding and functional profiles of the kratom alkaloids, suggesting potential utility for managing pain, but further studies are needed to follow up on these in vitro findings. All three kratom alkaloids tested inhibited select cytochrome P450 enzymes, suggesting a potential risk for adverse interactions when kratom is co-consumed with drugs metabolized by these enzymes.


Assuntos
Analgésicos/farmacologia , Mitragyna/química , Extratos Vegetais/química , Receptores Opioides mu/metabolismo , Alcaloides de Triptamina e Secologanina/farmacologia , Cromatografia Líquida , Humanos , Metabolômica , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Espectrometria de Massas em Tandem
13.
J Cell Biol ; 138(6): 1395-407, 1997 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-9298993

RESUMO

MEP21 is an avian antigen specifically expressed on the surface of Myb-Ets-transformed multipotent hematopoietic precursors (MEPs) and of normal thrombocytes. Using nanoelectrospray tandem mass spectrometry, we have sequenced and subsequently cloned the MEP21 cDNA and named the gene thrombomucin as it encodes a 571-amino acid protein with an extracellular domain typical of the mucin family of proteoglycans. Thrombomucin is distantly related to CD34, the best characterized and most used human hematopoietic stem cell marker. It is also highly homologous in its transmembrane/intracellular domain to podocalyxinlike protein-1, a rabbit cell surface glycoprotein of kidney podocytes. Single cell analysis of yolk sac cells from 3-d-old chick embryos revealed that thrombomucin is expressed on the surface of both lineage-restricted and multipotent progenitors. In the bone marrow, thrombomucin is also expressed on mono- and multipotent progenitors, showing an overlapping but distinct expression pattern from that of the receptor-type stem cell marker c-kit. These observations strengthen the notion that the Myb-Ets oncoprotein can induce the proliferation of thrombomucin-positive hematopoietic progenitors that have retained the capacity to differentiate along multiple lineages. They also suggest that thrombomucin and CD34 form a family of stem cell-specific proteins with possibly overlapping functions in early hematopoietic progenitors.


Assuntos
Antígenos de Superfície/genética , Plaquetas/química , Células-Tronco Hematopoéticas/química , Animais , Antígenos CD34/genética , Antígenos de Superfície/isolamento & purificação , Plaquetas/citologia , Células da Medula Óssea , Embrião de Galinha , Clonagem Molecular , DNA Complementar , Endotélio Vascular/química , Eritroblastos/química , Eritroblastos/citologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Células-Tronco Hematopoéticas/citologia , Rim/química , Rim/citologia , Macrófagos/química , Macrófagos/citologia , Espectrometria de Massas , Dados de Sequência Molecular , Proteínas Proto-Oncogênicas c-kit/genética , Homologia de Sequência de Aminoácidos , Linfócitos T/química , Linfócitos T/citologia
14.
Science ; 268(5210): 540-2, 1995 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-17756721

RESUMO

The link between H chondrites and silicate inclusions in group IIE iron meteorites has long been suspected, but direct evidence for a common parentage has remained elusive. The discovery of an unmelted chondritic inclusion in the Techado iron meteorite sheds light on the genetic relation between these two groups, providing clues on the origin of chondritic materials as inclusions in iron meteorites. It is proposed that the complex IIE iron meteorite breccias formed by collisions with several different bodies, followed by deep burial of metal and silicate fragments in the asteroidal megaregolith.

15.
Rehabilitation (Stuttg) ; 48(5): 288-97, 2009 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-19847725

RESUMO

BACKGROUND: Chronic low back pain (CLBP) is often associated with clinical and subclinical levels of psychological problems. A higher stage of chronicity is associated with an increase in co-existing psychological disorders. Previous programmes of inpatient orthopaedic rehabilitation reveal little evidence of sustained rehabilitation effects, a finding which may be attributable to the absence of specific psychological treatment during the programme. PURPOSE: Does cognitive-behavioural depression management training in patients with CLBP and depressive symptoms improve the inpatient orthopaedic rehabilitation success depending on the stage of chronicity? METHOD: Effects of the new programme on psychological well-being (ADS depressive symptoms, HADS anxiety, SCL somatization and mental health of the SF-12) were investigated in n=75 patients with first and second stage of chronicity immediately after, six months after and 24 months after rehabilitation and were compared to standard rehabilitation without management of depressive symptoms. RESULTS: All patients benefited from both treatments immediately after rehabilitation. However, six months after rehabilitation only patients of the intervention group showed significant beneficial effects with regard to depressive symptoms and mental health. The lowered depressive symptoms remained stable up to the 24-month follow-up assessment. Anxiety in the second stage of chronicity was reduced up to the 6-month follow-up and in the first stage up to the 24-month follow-up. CONCLUSIONS: The new programme with a cognitive-behavioural depression management training revealed beneficial effects on mental health in the mid-term and on depressive symptoms in the long-term. However, the effects need to be further improved by after-care programmes.


Assuntos
Dor nas Costas/psicologia , Dor nas Costas/reabilitação , Terapia Cognitivo-Comportamental/métodos , Depressão/psicologia , Depressão/reabilitação , Dor nas Costas/complicações , Doença Crônica , Depressão/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicologia , Resultado do Tratamento
16.
Clin Hemorheol Microcirc ; 71(2): 159-164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30562896

RESUMO

BACKGROUND: Renal cell carcinomas (RCC) represent a heterogeneous group of hypo- and hypervascularized malignancies. Using contrast-enhanced ultrasound (CEUS) specific imaging features of clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC) subtypes have been demonstrated. However, some RCCs show atypical imaging features making it difficult to distinguish between the subtypes. OBJECTIVE: This study was performed to evaluate the observed enhancement features of pRCC in CEUS and to assess the sensitivity in the diagnosis of suspected renal malignancies in a 10 year retrospective analysis at our institution. METHODS: The study population consisted of 60 patients with histologically confirmed pRCC. All patients underwent CEUS imaging between 2005 and 2015 as part of their diagnostic workup. RESULTS: In 45 out of 60 (75%) cases the examined pRCC showed typical hypoenhancement and wash-out. 15 out of 60 (25%) pRCC showed atypical enhancement features; in 14 cases the contrast enhancement indicated a ccRCC. 1 complex cyst was falsely reported as IIF lesion. 59 out of 60 malignancies were reported as malignant using CEUS resulting in a sensitivity of 98.4%. CONCLUSIONS: CEUS is an eligible imaging technique to visualize the contrast enhancement features of pRCC. However, up to 25% of pRCCs show an atypical enhancement pattern making it difficult to distinguish it from other renal lesions.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Meios de Contraste/uso terapêutico , Neoplasias Renais/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Curr Opin Genet Dev ; 2(2): 249-55, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1638119

RESUMO

Myb is a transcriptional activator protein with repeated helix-turn-helix DNA-binding motifs distantly related to the homeodomain. In hematopoiesis, c-myb appears to control both cell proliferation and differentiation. The mechanisms by which the leukemogenic potential of c-Myb is activated are complex and involve truncations, point mutations, and fusion or coexpression with other proteins.


Assuntos
Células-Tronco Hematopoéticas/citologia , Proteínas Proto-Oncogênicas/fisiologia , Proteínas Oncogênicas de Retroviridae/fisiologia , Fatores de Transcrição/fisiologia , Animais , Diferenciação Celular/genética , Divisão Celular/genética , Regulação da Expressão Gênica/fisiologia , Humanos , Proteínas Oncogênicas v-myb , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas c-myb , Proteínas Oncogênicas de Retroviridae/química , Fatores de Transcrição/química
18.
Curr Opin Genet Dev ; 8(5): 545-51, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9794826

RESUMO

Recent studies have shown that hematopoietic transcription factors can engage in multiple protein-protein interactions. Accumulating evidence indicates that specific complexes define differentiation lineages and differentiation stages. It is proposed that these complexes acquire new functions during blood cell differentiation through successive changes in composition - much as discussion topics of groups at a cocktail party take new directions as new people join and others leave.


Assuntos
Hematopoese/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Fatores de Transcrição/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Diferenciação Celular , Eritropoese/genética , Eritropoese/fisiologia , Hematopoese/genética , Células-Tronco Hematopoéticas/citologia , Modelos Biológicos
19.
Curr Biol ; 8(10): R353-5, 1998 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-9601636

RESUMO

The avian retroviruses E26 and AMV carry mutated versions of the gene encoding the cellular transcription factor c-Myb. Surprisingly, these two mutant forms of Myb differ in the subsets of myeloid cells that they transform, the target genes that they activate, and the way in which they are regulated.


Assuntos
Ciclofilinas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Transativadores/genética , Transativadores/metabolismo , Animais , Vírus da Mieloblastose Aviária/genética , Proteínas de Transporte/metabolismo , Diferenciação Celular , Transformação Celular Viral , Peptidil-Prolil Isomerase F , Regulação da Expressão Gênica , Vetores Genéticos , Mutação , Peptidilprolil Isomerase/metabolismo , Proteínas Proto-Oncogênicas c-myb , Retroviridae/genética
20.
Curr Biol ; 6(7): 866-72, 1996 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-8805301

RESUMO

BACKGROUND: The Myb-Ets protein encoded by the E26 acute avian leukemia virus is a paradigm for the function of fused transcriptional activator oncoproteins. Myb-Ets transforms hematopoietic progenitor cells (myb-Ets progenitors, MEPs) that can be induced to differentiate into eosinophilic and myeloid cells by the activation of pathways involving Ras and/or protein kinase C. The Ets portion of the fusion protein seems to be required to maintain the multipotency of MEPs: MEPs transformed with a temperature-sensitive E26 mutant with a lesion in Ets (ts 1.1) and shifted to the non-permissive temperature predominantly form erythroid cells, but also form eosinophilic and myeloid cells. This interpretation is complicated, however, by the observation that ts 1.1-transformed MEPs differ from MEPs transformed with wild-type E26 in that they expressed erythroid and eosinophil markers even at the permissive temperature. RESULTS: In order to alleviate the problems associated with the use of temperature-sensitive mutants we have designed a vector that allows the inducible deletion of the Ets domain. To this end, we introduced FLP recombinase target sites into the E26 virus on the 5' and 3' sides of Ets and included within the same retroviral vector sequences encoding and estrogen-dependent FLP recombinase. This construct, termed FRV-3, is capable of transforming cells to produce a phenotype indistinguishable from that of MEPs obtained with wild-type virus. Hormone treatment of MEPs transformed with FRV-3 induced erythroid differentiation in a subpopulation of the cells; this subpopulation was found to have completely excised ets. However, in contrast to previous results obtained with ts 1.1-transformed MEPs, no differentiation along the eosinophilic and myeloid lineages was seen in hormone-treated FRV-3-transformed MEPs. CONCLUSIONS: Our results demonstrate the feasibility of using a site-specific recombinase to excise a fused oncoprotein domain encoded by a retrovirus. More specifically, they show that the Ets portion of the Myb-Ets protein selectively inhibits differentiation of MEPs along the erythroid lineage, and suggests that Ets is also required for their differentiation along the eosinophil and, possibly, myeloid lineages.


Assuntos
DNA Nucleotidiltransferases/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Integrases , Proteínas Oncogênicas de Retroviridae/metabolismo , Animais , Diferenciação Celular , Linhagem Celular Transformada , Embrião de Galinha , Galinhas , Estradiol/análogos & derivados , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Fulvestranto , Globinas/genética , Globinas/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Humanos , Oncogenes , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Recombinases , Proteínas Oncogênicas de Retroviridae/genética
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