Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover.

The cell surface receptor Fas (FasR, Apo-1, CD95) and its ligand (FasL) are mediators of apoptosis that have been shown to be implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and one of the two major cytolytic pathways mediated by CD8+ cytolytic T cells. To gain further understanding of the Fas system., we have analyzed Fas and FasL expression during mouse development and in adult tissues. In developing mouse embryos, from 16.5 d onwards, Fas mRNA is detectable in distinct cell types of the developing sinus, thymus, lung, and liver, whereas FasL expression is restricted to submaxillary gland epithelial cells and the developing nervous system. Significant Fas and FasL expression were observed in several nonlymphoid cell types during embryogenesis, and generally Fas and FasL expression were not localized to characteristic sites of programmed cell death. In the adult mouse, RNase protection analysis revealed very wide expression of both Fas and FasL. Several tissues, including the thymus, lung, spleen, small intestine, large intestine, seminal vesicle, prostate, and uterus, clearly coexpress the two genes. Most tissues constitutively coexpressing Fas and FasL in the adult mouse are characterized by apoptotic cell turnover, and many of those expressing FasL are known to be immune privileged. It may be, therefore, that the Fas system is implicated in both the regulation of physiological cell turnover and the protection of particular tissues against potential lymphocyte-mediated damage.

Convenient synthesis of C75, an inhibitor of FAS and CPT1

C75 is a synthetic racemic α-methylene-γ-butyrolactone exhibiting anti-tumoral properties in vitro and in vivo as well as inducing hypophagia and weight loss in rodents. These interesting properties are thought to be a consequence of the inhibition of the key enzymes FAS and CPT1 involved in lipid metabolism. The need for larger amounts of this compound for biological evaluation prompted us to develop a convenient and reliable route to multigram quantities of C75 from easily available ethyl penta-3,4-dienoate 6. A recently described protocol for the addition of 6 to a mixture of dicyclohexylborane and nonanal followed by acidic treatment of the crude afforded lactone 8, as a mixture of cis and trans isomers, in good yield. The DBU-catalyzed isomerization of the methyl esters 9 arising from 8 gave a 10:1 trans/cis mixture from which the trans isomer was isolated and easily transformed into C75. The temporary transformation of C75 into a phenylseleno ether derivative makes its purification, manipulation and storage easier.

Inhibition of fas death signals by FLIPs.

The death receptor Fas is a member of the tumor necrosis factor receptor family; upon interaction with its ligand it efficiently activates caspases and induces apoptosis. Despite abundant Fas surface expression, however, Fas death-signals are frequently interrupted. Many viruses express antiapoptotic proteins, including caspase inhibitors, Bcl-2 homologues and death-effector-domain-containing proteins that are termed FLIPs (FLICE [Fas-associated death-domain-like IL-1beta-converting enzyme]-inhibitory proteins). Cellular homologues of these inhibitors have been identified. Cellular FLIPs structurally resemble caspase-8 except that they lack proteolytic activity. FLIPs are highly expressed in tumor cells, T lymphocytes and healthy, but not injured, myocytes; this suggests a critical role of FLIPs as endogenous modulators of apoptosis.

Convenient synthesis of C75, an inhibitor of FAS and CPT1

C75 is a synthetic racemic α-methylene-γ-butyrolactone exhibiting anti-tumoral properties in vitro and in vivo as well as inducing hypophagia and weight loss in rodents. These interesting properties are thought to be a consequence of the inhibition of the key enzymes FAS and CPT1 involved in lipid metabolism. The need for larger amounts of this compound for biological evaluation prompted us to develop a convenient and reliable route to multigram quantities of C75 from easily available ethyl penta-3,4-dienoate 6. A recently described protocol for the addition of 6 to a mixture of dicyclohexylborane and nonanal followed by acidic treatment of the crude afforded lactone 8, as a mixture of cis and trans isomers, in good yield. The DBU-catalyzed isomerization of the methyl esters 9 arising from 8 gave a 10:1 trans/cis mixture from which the trans isomer was isolated and easily transformed into C75. The temporary transformation of C75 into a phenylseleno ether derivative makes its purification, manipulation and storage easier.

Characterization of Fas (Apo-1, CD95)-Fas ligand interaction.

The death-inducing receptor Fas is activated when cross-linked by the type II membrane protein Fas ligand (FasL). When human soluble FasL (sFasL, containing the extracellular portion) was expressed in human embryo kidney 293 cells, the three N-linked glycans of each FasL monomer were found to be essential for efficient secretion. Based on the structure of the closely related lymphotoxin alpha-tumor necrosis factor receptor I complex, a molecular model of the FasL homotrimer bound to three Fas molecules was generated using knowledge-based protein modeling methods. Point mutations of amino acid residues predicted to affect the receptor-ligand interaction were introduced at three sites. The F275L mutant, mimicking the loss of function murine gld mutation, exhibited a high propensity for aggregation and was unable to bind to Fas. Mutants P206R, P206D, and P206F displayed reduced cytotoxicity toward Fas-positive cells with a concomitant decrease in the binding affinity for the recombinant Fas-immunoglobulin Fc fusion proteins. Although the cytotoxic activity of mutant Y218D was unaltered, mutant Y218R was inactive, correlating with the prediction that Tyr-218 of FasL interacts with a cluster of three basic amino acid side chains of Fas. Interestingly, mutant Y218F could induce apoptosis in murine, but not human cells.

Arvostus- ja jaksotussäännökset – FAS vs. IAS - suomalaiset pörssiyritykset 1997-2000

Tämän pro gradu –tutkielman teoriaosan tavoitteena on tutkia vertai-lemalla IAS-tilinpäätöstä (International Accounting Standards) ja IAS-standardeja, sekä vuosina 1993 ja 1997 voimaan tulleita kirjanpitolakeja, ja selvittää millaisia eroja näiden välillä on arvostus- ja jaksotus-säännöksien osalta. Empiirisessä osuudessa tavoitteena on tutkia, ovatko suomalaiset pörssiyhtiöt valinneet Suomen kirjanpitolaista sellaisia vaihtoehtoja, jotka ovat lähempänä IAS-standardeja (arvostus- ja jaksotussäännösten osalta). Tutkimuksen metodologia on lähinnä nomoteettista tutkimusotetta. Tutkimus on komparatiivista analyysiä kirjanpitolain ja IAS-tilinpäätöksen välillä. Tutkimuksessa käsitellään kaikki IAS-standardit, mutta tarkempi tarkastelu käydään arvostus- ja jaksotussäännösten osalta. Näitä eriä verrataan Suomen kirjanpitolain vastaaviin kohtiin. Empiirisessä osassa tutkitaan yritysten vuosikertomuksien avulla onko ns. IAS-yritysten ja FAS-yritysten (Finnish Accounting Standards) välillä eroja. Kuusi tarkastelussa mukana olevaa erää ovat arvostusmenetelmät, hankintameno, alimman arvon periaate, tutkimus- ja kehittämismenot, leasing ja eläkemenot. Eroja löytyy, joten monilla yrityksillä saattaa tulla vielä tulla kiire, sillä tilinpäätökset pitää tehdä IAS:n mukaisesti vuoteen 2005 mennessä

Transition : en betydelsefull fas i den långtidssjuka ungas vård

The aim of this caring science thesis is to deepen the understanding for the long-term ill adolescents care. In particular it aims to reach a better understanding of transition in health care, with a focus on how young people perceive health care. The goal is to build a model, a consistent theoretical framework that makes it possible to listen to the adolescent´s own voice, providing a better understanding of what good care consists in from their point of view. This Master's thesis consists of a literature overview on the concept of transition and a themed interview with young patients regarding transition of health care. The overall issue is 1. What is good care during the transition according to the adolescents themselves? 2. How does transition affect the young people's health and lives? The theoretical perspective of this thesis lies in the caring science tradition that has been developed at the Åbo Akademi University department of caring science with the caritative nursing theory as a basis. The epistemological and ontological assumptions are based on the caritative nursing theory, which in itself is ethical. Understanding of the concept of transition is based on A. Meleis transitions theory. The methodological approach is hermeneutical. The theme interview has been analyzed by using S. Kvales method. The material consists of a thematic interview with 10 long-term ill adolescents, about their views of the care received. This thesis research even in how NOBABs standards appears in the litterature as well as how they are implemented from the point of view of young people. The findings of this thesis shows that good care for the adolescent is a true presence with the young and an understanding of the direction in which the young move toward during the transition of care. Good care for an adolescent consists in being recognized as a person who is seen, known, appreciated and understood. Good care for the young involves recognizing her strength and joy of life including the contrast she experiences between health and suffering. To recognize their personal strength and courage supports the adolescents during the process of transitions of care Good care for the young involves responsibility for the individual person and humility in approaching her, giving attention to her view of life and aspirations. Openness and humility in the approach lays the foundation for a trusting relation during the transition of care. A unified theoretical framework is needed to promote the long-term ill adolescents care during transition of care. When the young and her individual needs is the centerpiece of healthcare creates this the basis for empowering care that supports the young in her quest for health. This master thesis adds a given model to the long-term ill adolescents` healthcare.

Expression of CD40 ligand, interferon-gamma and Fas ligand genes in endomyocardial biopsies of human cardiac allografts: correlation with acute rejection

The purpose of the present study was to investigate the expression (mRNA) of CD40 ligand (CD40L), interferon-gamma (IFN-gamma) and Fas ligand (FasL) genes in human cardiac allografts in relation to the occurrence of acute cardiac allograft rejection as well as its possible value in predicting acute rejection. The mRNA levels were determined by a semiquantitative reverse transcriptase-polymerase chain reaction method in 39 samples of endomyocardial biopsies obtained from 10 adult cardiac transplant recipients within the first six months after transplantation. Biopsies with ongoing acute rejection showed significantly higher CD40L, IFN-gamma and FasL mRNA expression than biopsies without rejection. The median values of mRNA expression in biopsies with and without rejection were 0.116 and zero for CD40L (P<0.003), 0.080 and zero for IFN-gamma (P<0.0009), and 0.156 and zero for FasL (P<0.002), respectively. In addition, the levels of IFN-gamma mRNA were significantly increased 7 to 15 days before the appearance of histological evidence of rejection (median of 0.086 in pre-rejection biopsies), i.e., they presented a predictive value. This study provides further evidence of heightened expression of immune activation genes during rejection and shows that some of these markers may present predictive value for the occurrence of acute rejection.

Effect of iodide on Fas, Fas-ligand and Bcl-w mRNA expression in thyroid of NOD mice pretreated with methimazole

Nonobese diabetic (NOD) mice and a derived strain, NOD.H.2h4, have been used as a model for experimental spontaneous thyroiditis and thyroiditis induced by iodide excess after a goiter-inducing period. Some authors have proposed that iodide, given after methimazole or propylthiouracil, is capable of inducing apoptosis in thyroid cells and that anti-thyroid drugs can modulate the expression of apoptosis components such as Fas and its ligand (Fas-L). Here we evaluated the effect of potassium iodide (20 µg/animal for 4 days, ip) given to NOD mice at the 10th week of life after exposure to methimazole (1 mg/ml) in drinking water from the 4th to the 10th week of life. Fas, Fas-L and Bcl-w expression were analyzed semiquantitatively by RT-PCR immediately after potassium iodide administration (group MI44D) or at week 32 (MI32S). Control groups were added at 10 (C10) and 32 weeks (C32), as well as a group that received only methimazole (CM10). An increase in the expression of Fas-L and Bcl-w (P<0.01, ANOVA) was observed in animals of group MI44D, while Fas was expressed at higher levels (P = 0.02) in group C32 (72.89 ± 47.09 arbitrary units) when compared to group C10 (10.8 ± 8.55 arbitrary units). Thus, the analysis of Fas-L and Bcl-w expression in the MI44D group and Fas in group C32 allowed us to detect two different patterns of expression of these apoptosis components in thyroid tissue of NOD mice.

Efecto de la infección bacteriana en la evolución de la artritis en el ratón MRL

Tesis (Doctorado en Ciencias con Especialidad en Inmunología) UANL

Participación de la vía Fas-I

Tesis (Doctor en Ciencias con Acentuación en Microbiología) UANL, 2010.

Escoleta Gianni Rodari, projecte : en fas una mossegada més?. 'Guardería Gianni Rodari, proyecto : ¿das un mordisco más?'.

Se expone un proyecto que lleva a cabo la escoleta Gianni rodari, en este curso el proyecto se centra en la alimentación, a través de este proyecto basado en la investigación-observación se quieren extraer una serie de reflexiones para poder mejorar la práctica cotidiana.

Análisis de los repertorios de acción política del Movimiento Revolucionario Liberal (MRL) durante el Frente Nacional (1958-1966)

El presente Estado del Arte constituye una revisión sistemática desde la Ciencia Política de un problema previamente delimitado por la historiografía política del siglo XX en Colombia: el de la acción política de movimientos políticos disidentes durante el Frente Nacional. Para ello, se ha recurrido a una propuesta proveniente de la teoría del proceso teórico, que sistematice y ordene aquellos elementos que constituyeron el eje de la movilización política y social del Movimiento Revolucionario Liberal, en un contexto caracterizado por la institucionalización de mecanismos de exclusión política y de bloqueo a las reivindicaciones sociales.