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1.
Phys Rev Lett ; 122(9): 092701, 2019 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-30932526

RESUMEN

We report the first measurement of low-energy proton-capture cross sections of ^{124}Xe in a heavy-ion storage ring. ^{124}Xe^{54+} ions of five different beam energies between 5.5 and 8 AMeV were stored to collide with a windowless hydrogen target. The ^{125}Cs reaction products were directly detected. The interaction energies are located on the high energy tail of the Gamow window for hot, explosive scenarios such as supernovae and x-ray binaries. The results serve as an important test of predicted astrophysical reaction rates in this mass range. Good agreement in the prediction of the astrophysically important proton width at low energy is found, with only a 30% difference between measurement and theory. Larger deviations are found above the neutron emission threshold, where also neutron and γ widths significantly impact the cross sections. The newly established experimental method is a very powerful tool to investigate nuclear reactions on rare ion beams at low center-of-mass energies.

2.
Phys Rev Lett ; 119(16): 163401, 2017 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-29099197

RESUMEN

Electronic stopping of slow protons in ZnO, VO_{2} (metal and semiconductor phases), HfO_{2}, and Ta_{2}O_{5} was investigated experimentally. As a comparison of the resulting stopping cross sections (SCS) to data for Al_{2}O_{3} and SiO_{2} reveals, electronic stopping of slow protons does not correlate with electronic properties of the specific material such as band gap energies. Instead, the oxygen 2p states are decisive, as corroborated by density functional theory calculations of the electronic densities of states. Hence, at low ion velocities the SCS of an oxide primarily scales with its oxygen density.

3.
Monatsh Chem ; 148(5): 871-877, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28458401

RESUMEN

ABSTRACT: A stringent limitation in many optoelectronic devices, such as solar cells and light emitting diodes, is the intrinsic need for a transparent electrode. Uniting relevant aspects, indium tin oxide (ITO) is often the material of choice, however, alternatives are sought and being in particular found in conductive polymers. In this work, we present a novel doping strategy to arrive at highly conducting polymeric material based on poly-3,4-ethylenedioxythiophene (PEDOT). Based on commercial high conductivity PEDOT:PSS (Clevios PH 1000), and a post processing with aqueous triflic acid delivers a material that is both transparent and of low resistivity (5.23 × 10-4 Ω cm). Furthermore, this material retains its conductive character over a large temperature range, indicating metallic behaviour. This is further supported by positive magnetoconductance effects at low temperatures (1.8-10 K) and extended mean free paths of the conduction electrons are observed-evidencing for a metallic state in this polymer.

4.
Phys Rev Lett ; 118(10): 103401, 2017 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-28339263

RESUMEN

The electronic stopping cross sections (SCS) of Ta and Gd for slow protons have been investigated experimentally. The data are compared to the results for Pt and Au to learn how electronic stopping in transition and rare earth metals correlates with features of the electronic band structures. The extraordinarily high SCS observed for protons in Ta and Gd cannot be understood in terms of a free electron gas model, but are related to the high densities of both occupied and unoccupied electronic states in these metals.

5.
Nervenarzt ; 86(7): 872-83, 2015 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-25740384

RESUMEN

In this article we develop a phenomenological psychopathology of receding delusions in persons with a diagnosis of schizophrenia. Drawing on Klaus Conrad's (1905-1961) descriptions of beginning schizophrenia and an in-depth single case study, we develop descriptions of the process of receding delusions as opposed to ongoing delusions in the manner of a double-orientation to reality. We distinguish two stages in this process of social recovery and term these stages deactualization and orthostrophy. We argue that delusional convictions lose importance and persuasive power if they are no longer supported by corresponding value apprehensions or perceptions and perception-like experiences (i.e. hallucinations). Consequently, we propose that the process of receding delusions proceeds in layers comparable to a regression of the process of upcoming delusions. Lastly we discuss both stages of receding delusions (deactualization and orthostrophy) and ongoing delusions (double-orientation to reality) as possible continuous manners of social recovery concerning delusional psychosis (diagnosis of schizophrenia) and argue for specific interventions according to these different continuous manners.


Asunto(s)
Deluciones/diagnóstico , Deluciones/psicología , Modelos Psicológicos , Trastornos Psicóticos/psicología , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Deluciones/terapia , Alemania , Humanos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/terapia , Esquizofrenia/terapia
6.
Leukemia ; 27(9): 1841-51, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23797473

RESUMEN

Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS-MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS-MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS.


Asunto(s)
Células Madre Mesenquimatosas/metabolismo , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Diferenciación Celular , Proliferación Celular , Senescencia Celular , Análisis por Conglomerados , Ensayo de Unidades Formadoras de Colonias , Metilación de ADN , Epigénesis Genética , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunofenotipificación , Masculino , Células Madre Mesenquimatosas/citología , Persona de Mediana Edad , Osteogénesis/genética , Fenotipo
7.
Transplant Proc ; 45(1): 335-41, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23267815

RESUMEN

BACKGROUND: Jehovah's Witnesses (JW) refuse to receive blood products due to their religious beliefs. Bloodless transplantation programs have made the successful transplantation of solid organs like heart, liver, kidney, and pancreas in JW feasible. In this study we present the third and fourth case of a successful bloodless lung transplantation and analyze perioperative parameters and outcome with a strictly selected matched control group (CG). METHODS: Two JW patients suffering from idiopathic pulmonary fibrosis had single lung transplantation in the transfusion-free program. Ten of 113 patients (8.8%) undergoing lung transplantation fulfilled the matching criteria and served as CG. Perioperative parameters including blood loss and transfusions were collected from the charts. Regarding outcome parameters arterial blood gas, lung function testing, length of stay, and survival were analyzed. RESULTS: Concerning perioperative parameters no significant differences could be found between both groups except for the creatinine level, which was significantly lower in the JW group on postoperative day 0 (P = .037), and the hemoglobin and hematocrit levels, which were significantly higher in the JW group on postoperative day 3 (P = .032 and P = .041, respectively). The analysis of the outcome parameters revealed significantly higher postoperative lung functional testing values forced expiratory volume after 1 second (FEV1) and forced vital capacity (FVC) in the JW group compared with the CG (P = .037 and P = .036, respectively). CONCLUSION: Bloodless lung transplantation is feasible in carefully selected JW recipients. Comparing JW to CG, no statistically significant difference in the perioperative course and a trend towards a favorable postoperative lung function outcome were detected.


Asunto(s)
Actitud Frente a la Salud , Fibrosis Pulmonar Idiopática/cirugía , Testigos de Jehová , Trasplante de Pulmón/métodos , Anciano , Transfusión Sanguínea , Estudios de Casos y Controles , Cuidados Críticos , Femenino , Volumen Espiratorio Forzado , Humanos , Tiempo de Internación , Masculino , Oxígeno/metabolismo , Aceptación de la Atención de Salud , Periodo Perioperatorio , Factores de Tiempo , Resultado del Tratamiento , Capacidad Vital
8.
Nervenarzt ; 83(1): 84-6, 89-91, 2012 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-21845449

RESUMEN

Using Jaspers' methodically critical attitude (methodenkritische Einstellung) we distinguish three aspects of his understanding of psychotherapy: (1) psychotherapy gains scientific quality via methodical strictness (and is therefore independent of a therapist's weltanschauung); (2) psychotherapy is a (more or less) 'hermeneutical' method of self-enlightenment, offering limited statements with respect to one's life conduct; and (3) psychotherapy oversteps its epistemological limits if gaining the status of a weltanschauung, instead of leading to (existential) philosophizing in the face of transcendence. Following Jaspers we try to answer the question: What are the limits of psychotherapeutic methods with respect to questions of life conduct? The most important limit is the unbreakable linkage between the style of one's life conduct and the (personally) experienceable (superpersonal) sense of life, which cannot be disrupted with the means of any justifiable belief or falsifiable knowledge. Quite to the contrary, this existential linkage is the starting point of many psychotherapeutic interventions.


Asunto(s)
Trastornos Mentales/psicología , Trastornos Mentales/terapia , Psicoterapia/métodos , Psicoterapia/tendencias , Humanos
9.
Dtsch Med Wochenschr ; 134 Suppl 6: S234-6, 2009 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-19834853

RESUMEN

Quality control and performance improvement in the US health care system are based on several pillars: external review is performed by either government agencies, insurance companies, or public media. In cardiac surgery the STS database forms the backbone of most of these reviews. Internal review is based on providing outcome data, establishing benchmarks for performance, and root-cause analysis of adverse events. Peer review is used to analyze major issues in providing care. Transparency of the process and of outcome numbers generated is key for the success of measurements to improve performance. Finally, education of all health care providers in the hospital is needed to provide quality care and good outcomes. Maintaining proficiency of physicians and hospital personal in pathways and procedures requires constant educational efforts and clear pathways and guidelines. Growing resources have to be dedicated to quality management. As outcome data become essential in obtaining insurance contracts and government certification the investing into a comprehensive quality assurance program will pay off.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/normas , Garantía de la Calidad de Atención de Salud/organización & administración , Acreditación/normas , Procedimientos Quirúrgicos Cardíacos/economía , Educación Continua/normas , Hospitales Especializados/normas , Humanos , Revisión por Expertos de la Atención de Salud , Personal de Hospital/educación , Personal de Hospital/normas , Reembolso de Incentivo , Estados Unidos
10.
Colorectal Dis ; 5(3): 222-7, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12780882

RESUMEN

OBJECTIVE: Pilonidal sinus is common. It causes substantial loss of working hours. The major disadvantage of open wound treatment is the long time required for healing. Primary wound closure is on the other hand often followed by infection. A controlled, multicentre trial was carried out to evaluate the efficacy of a new gentamicin collagen fleece (Septocoll) combined with primary closure. PATIENTS AND METHODS: One hundred and three patients (88 men, 15 women, median age 30 years) were included. Fifty-one were randomised to gentamicin fleece plus primary closure (Genta Group), and 52 patients to open treatment alone (Open Group). RESULTS: The median interval to wound healing was 17 days in the Genta group and 68 days in the Open group (P = 0.0001, log-rank test). Two patients in Group 1 developed infection within the first two weeks, requiring reopening of the wound, with primary wound healing occurring in 73%. Failure of primary healing (27%) was usually due to seroma or spontaneous dehiscence which subsequently healed. CONCLUSION: The combination of gentamicin collagen fleece (Septocoll) with primary closure resulted in a shorter period to healing than the open technique without unwanted effects.


Asunto(s)
Antibacterianos/uso terapéutico , Colágeno/uso terapéutico , Gentamicinas/uso terapéutico , Seno Pilonidal/cirugía , Complicaciones Posoperatorias , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Cicatrización de Heridas/efectos de los fármacos , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo
12.
J Heart Lung Transplant ; 20(4): 457-64, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11295584

RESUMEN

BACKGROUND: The cellular and structural changes that occur during long-term ventricular unloading leading to cardiac recovery are poorly understood. However, we have previously demonstrated that left ventricular assist device (LVAD) support leads to a significant decrease in intracardiac tumor necrosis factor-alpha (TNF-alpha), a protein capable of producing hypertrophy and fibrosis. METHODS: To further define the beneficial effects of long-term ventricular unloading on cardiac function, we determined the effect of mechanical circulatory support on fibrosis and hypertrophy in paired myocardial samples of 18 patients with end-stage cardiomyopathy obtained at the time of LVAD implantation and removal. RESULTS: We determined total collagen as well as collagen I and III by a semiquantitative analysis of positive immune-stained areas in pre- and post-LVAD myocardial samples. We found that total collagen content was reduced by 72% (p < 0.001), whereas collagen I content decreased by 66% (p < 0.001) and collagen III content was reduced by 62% (p < 0.001). Next, we determined myocyte size by direct analysis of cellular dimensions utilizing a computerized edge detection system in pre- and post-LVAD myocardial samples. We found that myocyte size decreased in all patients studied for an average reduction of 26% (33.1 +/- 1.32 to 24.4 +/- 1.64 microm, p < 0.001). CONCLUSION: These data demonstrate that long-term mechanical circulatory support significantly reduces collagen content and decreases myocyte size. We suggest that the reduction of fibrosis and hypertrophy observed may in part contribute to the recovery of cardiac function associated with long-term mechanical circulatory support.


Asunto(s)
Cardiomiopatía Hipertrófica/terapia , Colágeno/metabolismo , Corazón Auxiliar , Miocardio/patología , Adulto , Análisis de Varianza , Cardiomiopatía Hipertrófica/metabolismo , Cardiomiopatía Hipertrófica/fisiopatología , Tamaño de la Célula , Femenino , Fibrosis , Humanos , Masculino , Persona de Mediana Edad , Miocardio/citología
13.
Rofo ; 172(6): 509-13, 2000 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-10916546

RESUMEN

PURPOSE: Evaluation of arthroscopically assisted reconstruction of the anterior cruciate ligament using ligamentum patellae autografts in the bone-tendon-bone technique with special regard to the position of blocks and interference screws. MATERIAL AND METHODS: In a prospective study 28 patients were included after undergoing arthroscopic anterior cruciate ligament replacement surgery. Data thus obtained were correlated with the postoperatively determined functional parameters of the affected joint. RESULTS: Interference screws, bone-blocks and ligamentous transplants could be well imaged using CT. In a comparison of our data with clinical results there was a statistically highly significant correlation between clinical outcome and the position of bone-blocks and interference screws in the tibia. Angles between screw and bone-block exceeding a standard deviation led to significantly worse results, while a divergence in femoral angles did not lead to significantly worse results. CONCLUSION: The postoperative study of anterior cruciate ligament replacement surgery by CT enables the evaluation of the transplant as well as the position of bone-blocks and interference screws.


Asunto(s)
Ligamento Cruzado Anterior/diagnóstico por imagen , Tornillos Óseos , Trasplante Óseo/diagnóstico por imagen , Ligamento Rotuliano/trasplante , Tomografía Computarizada por Rayos X , Adulto , Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior , Artroscopía , Trasplante Óseo/estadística & datos numéricos , Distribución de Chi-Cuadrado , Fémur/diagnóstico por imagen , Fémur/cirugía , Humanos , Masculino , Ligamento Rotuliano/diagnóstico por imagen , Periodo Posoperatorio , Estudios Prospectivos , Tibia/diagnóstico por imagen , Tibia/cirugía , Trasplante Autólogo/métodos
14.
Am J Surg ; 180(6): 498-501; discussion 501-2, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11182406

RESUMEN

BACKGROUND: To define the beneficial cellular changes that occur with chronic ventricular unloading, we determined the effect of left ventricular assist device (LVAD) placement on myocardial fibrosis. METHODS: We obtained paired myocardial samples (before and after LVAD implantation) from 10 patients (aged 43 to 64 years) with end-stage cardiomyopathy. We first determined regional collagen expression of an explanted heart by a computerized semiquantitative analysis of positive picro-sirius red stained areas. RESULTS: We found that there was no statistically significant difference in collagen content between regions of the failed heart studied. Next we determined collagen content in these paired myocardial biopsies pre- and post-LVAD implantation. All 10 patients had significant reductions in collagen content after LVAD placement with a mean reduction of 82% (percent of tissue area stained decreased from 32% +/- 4% to 4% +/- 0.8%, P < 0.001). CONCLUSION: In summary, these data demonstrate that chronic mechanical circulatory support significantly reduces fibrosis in the failing myocardium.


Asunto(s)
Colágeno/análisis , Corazón Auxiliar , Miocardio/química , Adulto , Cardiomiopatía Dilatada/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/cirugía , Miocardio/patología
15.
Chromosoma ; 108(2): 83-94, 1999 May.
Artículo en Inglés | MEDLINE | ID: mdl-10382070

RESUMEN

The chromatin protein Polycomb (PC) is necessary for keeping homeotic genes repressed in a permanent and heritable manner. PC is part of a large multimeric complex (PcG proteins) involved in generating silenced chromatin domains at target genes, thus preventing their inappropriate expression. In order to assess the intranuclear distribution of PC during mitosis in different developmental stages as well as in the germ line we generated transgenic fly lines expressing a PC-GFP (Green Fluorescent Protein) fusion protein. Rapidly dividing nuclei were found to display a rather homogeneous PC-GFP distribution. However, with increasing differentiation a pronounced subnuclear pattern was observed. In all investigated diploid somatic tissues the bulk of PC-GFP fusion protein is depleted from the chromosomes during mitosis: however, a detectable fraction remains associated. In the male germ line in early spermatogenesis, PC-GFP was closely associated with the chromosomal bivalents and gradually lost at later stages. Interestingly, we found that PC is associated with the nucleolus in spermatocytes, unlike somatic nuclei. In contrast to mature sperm showing no PC-GFP signal the female germ line retains PC in the germinal vesicle.


Asunto(s)
Núcleo Celular/metabolismo , Proteínas de Drosophila , Drosophila melanogaster/metabolismo , Proteínas de Insectos/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Animales , Animales Modificados Genéticamente , Drosophila melanogaster/embriología , Femenino , Células Germinativas , Proteínas Fluorescentes Verdes , Proteínas de Insectos/genética , Interfase , Proteínas Luminiscentes/genética , Masculino , Microscopía Fluorescente , Complejo Represivo Polycomb 1 , Proteínas Recombinantes de Fusión/genética
16.
Neuroreport ; 10(7): 1593-8, 1999 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-10380987

RESUMEN

We determined the independent effects of hypoxia, glucose deprivation and ischemia (hypoxia plus glucose deprivation) on steady-state levels of mRNA coding for specific nuclear and mitochondrially encoded enzymes of oxidative metabolism in cultured rat neurons and glia. Neither hypoxia nor low glucose alone changed steady-state message levels for any transcript. However, ischemia induced a biphasic effect on mitochondrially encoded transcripts for cytochrome oxidase subunit two (CO2) and the subunits 8 and 6 of ATPase (A 8/6), initially decreasing and then increasing mRNA levels to or above the levels recorded prior to ischemia. In contrast, three nuclear encoded transcripts for mitochondrial proteins were decreased by ischemia. These data demonstrate a lack of coordination between the expression of nuclear and mitochondrial genes in the initial response to ischemia and suggest that a selective, primary reaction to brain cell insults exists within the mitochondrion.


Asunto(s)
Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , ARN Mensajero/metabolismo , ARN/metabolismo , Animales , Supervivencia Celular/fisiología , Células Cultivadas , Femenino , Código Genético , Glucosa/metabolismo , Hipoxia Encefálica/metabolismo , Masculino , ARN Mitocondrial , Ratas , Ratas Sprague-Dawley
17.
Metabolism ; 48(4): 422-31, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10206432

RESUMEN

Brain cells are dependent on glucose and oxygen for energy. We investigated the effects of hypoxia, glucose deprivation, and hypoxia plus glucose deprivation on mRNA and protein levels of glucose transporter (GLUT1) and GLUT3 and 2-deoxyglucose (2-DG) uptake in primary cultures of rat neurons and astroglia. Hypoxia for 24 hours did not significantly affect cell viability but increased neuronal GLUT1 and GLUT3 mRNA up to 40-fold and fivefold, respectively, above control levels. Similar changes in GLUT1 mRNA were measured in glia. The effects of hypoxia on GLUT1 and GLUT3 mRNA were reversible. The increase in GLUT1 mRNA could be detected within 20 minutes of hypoxia and was blocked by actinomycin D. Nuclear runoff transcription assays showed that hypoxia did not alter the transcription rate of GLUT1. However, hypoxia enhanced the stability of GLUT1 mRNA in neurons (half-life [t(l/2)] > 12 hours) compared with normoxic conditions (t(1/2) approximately 10.4 hours), suggesting the existence of a posttranscriptional mechanism for the regulation of GLUT1 transcript levels. Twenty-four hours of normoxia and 1.0 mmol/L glucose increased neuronal GLUT1 mRNA less than threefold above basal, but 24 hours of glucose and oxygen deprivation increased GLUT1 over 111-fold above basal. Induction of neuronal GLUT1 mRNA was temporally associated with increased levels of GLUT1 protein and with stimulation of intracellular 2-DG accumulation. We conclude that hypoxia reversibly increases the transcript levels of GLUT1 and GLUT3 in rat brain cells and stimulates GLUT1 transcript levels by posttranscriptional mechanisms. Although glucose deprivation alone produces minimal effects on GLUT mRNA levels, hypoxia plus glucose deprivation synergize to markedly increase GLUT gene expression.


Asunto(s)
Glucemia/fisiología , Química Encefálica/fisiología , Hipoxia de la Célula/fisiología , Proteínas de Transporte de Monosacáridos/biosíntesis , Proteínas del Tejido Nervioso , Animales , Northern Blotting , Supervivencia Celular , Células Cultivadas , Desoxiglucosa/metabolismo , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/fisiología , Transportador de Glucosa de Tipo 1 , Transportador de Glucosa de Tipo 3 , Proteínas de Transporte de Monosacáridos/genética , Neuroglía/metabolismo , Neuronas/metabolismo , Consumo de Oxígeno/fisiología , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley
18.
Proc Natl Acad Sci U S A ; 95(23): 13703-8, 1998 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-9811864

RESUMEN

The importance of the amyloid precursor protein (APP) in the pathogenesis of Alzheimer's disease (AD) became apparent through the identification of distinct mutations in the APP gene, causing early onset familial AD with the accumulation of a 4-kDa peptide fragment (betaA4) in amyloid plaques and vascular deposits. However, the physiological role of APP is still unclear. In this work, Drosophila melanogaster is used as a model system to analyze the function of APP by expressing wild-type and various mutant forms of human APP in fly tissue culture cells as well as in transgenic fly lines. After expression of full-length APP forms, secretion of APP but not of betaA4 was observed in both systems. By using SPA4CT, a short APP form in which the signal peptide was fused directly to the betaA4 region, transmembrane domain, and cytoplasmic tail, we observed betaA4 release in flies and fly-tissue culture cells. Consequently, we showed a gamma-secretase activity in flies. Interestingly, transgenic flies expressing full-length forms of APP have a blistered-wing phenotype. As the wing is composed of interacting dorsal and ventral epithelial cell layers, this phenotype suggests that human APP expression interferes with cell adhesion/signaling pathways in Drosophila, independently of betaA4 generation.


Asunto(s)
Precursor de Proteína beta-Amiloide/genética , Drosophila melanogaster/genética , Endopeptidasas/genética , Regulación de la Expresión Génica , Genes de Insecto , Secretasas de la Proteína Precursora del Amiloide , Animales , Animales Modificados Genéticamente , Ácido Aspártico Endopeptidasas , Adhesión Celular/genética , Humanos , Fenotipo
19.
Wound Repair Regen ; 4(2): 269-77, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-17177824

RESUMEN

Transforming growth factor-beta1 appears to play important roles in normal wound healing by increasing synthesis of extracellular matrix components. However, the role of transforming growth factor-beta1 in the production of excessive scar tissue by fibroblasts from stenotic lesions of the larynx has not been evaluated. We examined the effect of transforming growth factor-beta1 on the steady-state messenger RNA levels of elastin, alpha2(l) procollagen, and lysyl oxidase (the enzyme that cross-links both of these structural proteins) in cell cultures of diploid human fibroblasts established from fetal skin, newborn foreskin, and an adult laryngeal stenotic lesion. Time-course and dose-response experiments demonstrated that treatment with 500 pmol/L transforming growth factor-beta1 for 20 hours induced maximal levels of mRNA for elastin (7- to 59-fold) and alpha2(l) procollagen (1.7- to 2.4-fold) in all three cultures of fibroblasts. Transforming growth factor-beta1 also increased levels of lysyl oxidase mRNA in fibroblasts cultured from newborn foreskin (2.4-fold) and a stenotic lesion (10-fold) but had minimal effects on the fibroblasts cultured from fetal skin (1.1-fold), which constitutively expressed high levels of lysyl oxidase mRNA. Furthermore, the fibroblast culture established from a laryngeal stenotic lesion responded with the highest fold-induction for all three mRNAs. Inhibition of mRNA synthesis by actinomycin D showed that transcription was required for transforming growth factor-beta1 induction of elastin, alpha2(l) procollagen, and lysyl oxidase mRNA in all three cultures of fibroblasts. Inhibition of protein synthesis by cycloheximide showed that translation was required for maximal induction by transforming growth factor-beta1 of elastin mRNA but had no observable effect on alpha2(l) procollagen mRNA in all three cultures of fibroblasts. In addition, translation was required for maximal induction of the lysyl oxidase mRNA by transforming growth factor-beta1 in the fibroblasts cultured from a stenotic lesion but not for fibroblast cultures established from fetal and adult skin. These results show that transforming growth factor-beta1 coordinately increases mRNA levels for the structural extracellular matrix proteins collagen and elastin, as well as for the cross-linking enzyme, lysyl oxidase. These data also support the hypothesis that transforming growth factor-beta1 may contribute to the formation of laryngeal stenotic lesions.

20.
Curr Genet ; 27(6): 528-35, 1995 May.
Artículo en Inglés | MEDLINE | ID: mdl-7553937

RESUMEN

One of the most important rice pathogens is Fusarium moniliforme (perfect stage: Gibberella fujikuroi), the causal agent of the super-elongation ("bakanae") disease. Thirty-seven strains of this species from different geographical regions were analyzed for their ability to produce gibberellins (GA) and for genetic relatedness by random amplified polymorphic DNA (RAPD). All GA-producing isolates showed nearly identical RAPD patterns using 51 oligonucleotide nona- and deca-mers as arbitrary primers. On the other hand, large differences between GA-nonproducing isolates were obtained. Comparison of the RAPD patterns with those of the tester strains of the six known mating populations (A, B, C, D, E, F) of G. fujikuroi showed that all producer strains belong to mating population C and all nonproducer isolates to other mating populations. Evidence for the usefulness of the RAPD technique to distinguish between mating populations was provided by sexual crossings. Consensus phylogenetic trees based on RAPDs were constructed by the Phylogenetic Analysis Using Parsimony (PAUP) system. In combination with morphological analysis, RAPD can distinguish between different species of the genus Fusarium. These investigations may find an application in the diagnosis of unknown Fusarium spp. and in distinguishing isolates of G. fujikuroi within the section Liseola.


Asunto(s)
ADN de Hongos/genética , Fusarium/genética , Gibberella/genética , Secuencia de Bases , Cruzamientos Genéticos , Cartilla de ADN/genética , Fusarium/clasificación , Fusarium/metabolismo , Marcadores Genéticos , Variación Genética , Gibberella/aislamiento & purificación , Gibberella/metabolismo , Giberelinas/biosíntesis , Datos de Secuencia Molecular , Filogenia , Polimorfismo Genético , Técnica del ADN Polimorfo Amplificado Aleatorio , Especificidad de la Especie
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