He putiputi, he taonga, he rangatira : the factors motivating young Maori women to achieve success : a thesis presented in partial fulfilment of the requirements for the degree of Master of Social Work at Massey University, Palmerston North, New Zealand

This thesis is a study of the factors that motivate young Māori women to achieve success. Six Māori women aged between fifteen and twenty six years were interviewed for the purpose of identifying what motivates them and to explore their perceptions of motivation, achievement and success. All of the young women have achieved across many facets within their lives but were chosen for this study because of their high achievements in sport, education and business. Jodi Te Huna, Kayla Sharland, Hinurewa Poutu, Amanda Gimblett, Christall Raukawa Lowe and Te Kaihou Ngarotata are the voices within this research. Their experiences, perceptions and ideas about motivation and achieving success are presented as case studies. Informed by a Māori worldview, Maāori research methodologies are blended together and are the foundation of this research. Grounded theory and Feminist approaches to research were also utilised alongside Māori methodologies which provide the researcher with the path to navigate the research process. The six Māori women who participated in this study are the heart of this research and through their voices they offer knowledge enabling the researcher to walk the path. The research found that a supportive environment is essential in motivating people. Whānau were identified as the primary external motivating factor which reflected a wide range of support systems. Using social learning theories to explain the internal intricacies of why we behave in a motivated way, the study found that the participants within this research were driven by intrinsic factors and instilled values which influenced them to behave in a motivated way. Self efficacy was also a factor motivating them to achieve their successes. The study also found a clear connection between external and internal motivating factors. Specifically, external motivating factors cultivate internal motivating factors. This study has been undertaken by a Māori woman, for and on behalf of Māori women. It contributes to the growing voice that Māori women are carving out in research and provides evidence that Māori women do achieve, can achieve and will continue to achieve

The interaction between C 5a and both C 5a R and C 5 L 2 receptors is required for production of G ‐ CSF during acute inflammation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99020/1/eji2635.pd

Modulation of inflammation by interleukin‐27

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141977/1/jlb1159.pd

Therapeutic potential of targeting IL‐17 and IL‐23 in sepsis

Severe sepsis is a major concern of public health in industrialized countries. It is estimated that in the United States 200,000‐400,000 cases occur annually and resulting in an extensive burden for the health care systems. To date, no FDA‐approved pharmacologic agents for the treatment or prevention of human sepsis are available. The current modalities of therapy in sepsis include the standard arsenal of supportive interventions in critical care medicine and pharmacotherapy, with use of antibiotics and catecholamines. Despite such efforts, the mortality rates of sepsis have remained around 30‐50 %. Extensive scientific studies have utilized animal models of disease and aimed for a better understanding of the pathophysiologic mechanisms during sepsis. Members of the IL‐17 family of cytokines, as well as the functionally related IL‐23, have been identified as new players in the molecular events during sepsis. Strategies for targeting these mediators with neutralizing antibodies during experimental sepsis in rodents have demonstrated efficacy, resulting in improved survival outcomes. Currently, it is not clear whether such findings can be translated to human sepsis. This review highlights the current knowledge on the biology of IL‐17 isoforms and IL‐23 as well as potential applications to clinical medicine.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155453/1/ctm22001132614.pd

SYNTHESIS OF GLYCOPROTEIN, GLYCOLIPID, PROTEIN, AND LIPID IN SYNCHRONIZED L5178Y CELLS

Synthesis of four macromolecular classes found in membranes—glycoprotein, glycolipid, protein, and lipid—was measured as a function of time of the cell cycle in synchronized L5178Y cells. Incorporation of leucine, choline, fucose, glucosamine, or thymidine into the cells, protein, nucleic acid, or lipid was measured by pulse-labeling for ½ hr at ½ hr intervals after release from the mitotic block. The amount of protein, lipid, glycoprotein, or glycolipid released or secreted into the medium by the L5178Y cells was also measured as a function of time of the cell cycle. Cellular protein was found to be synthesized throughout the cell cycle, with the highest synthesis occurring in the S period; synthesis was depressed in the M period. Cellular glycoprotein was synthesized at approximately the same times as protein, except that the rates of glycoprotein synthesis in the S period relative to other periods were much greater than for protein. Secreted protein was synthesized throughout the cell cycle without any general pattern, except that secretion was elevated in the late S and G2 periods. Secreted glycoprotein was similar to secreted protein. Cellular lipid and cellular glycolipid were synthesized almost exclusively in the G2 and M periods; there was no synthesis in the G1 and S periods. Release or secretion of glycolipid and lipid also occurred in the G2 and M periods

Untersuchungen über die Regulation der Genexpression von Interleukin-18-Bindungsprotein und Interleukin-18

Interleukin-18-Bindungsprotein (IL-18BP) ist ein erst kürzlich entdeckter Gegenspieler von Interleukin-18 (IL-18). Aufgrund der Eigenschaft von IL-18BP mit hoher Affinität an IL-18 zu binden, wird IL-18 neutralisiert und seine biologischen Wirkungen durch IL-18BP inhibiert. Das Zytokin IL-18 ist ein multifunktioneller Botenstoff des Immunsystems, dessen Aktivität bei der Entstehung von Entzündungen, der Abwehr von Infektionen und der Rückbildung von Tumoren beteiligt sein kann. Eine der bedeutendsten Wirkungen von IL-18 ist insbesondere seine Fähigkeit die Produktion und Freisetzung von Interferon-gamma durch T-Helfer Typ 1 (Th1) Zellen, Natürliche Killer (NK) Zellen und CD8+ zytotoxische Zellen auszulösen. Bislang war lediglich bekannt, dass es sich bei IL-18BP um ein konstitutiv exprimiertes und sezerniertes Protein handelt. Die Zielsetzung dieser Promotionsarbeit war es zu untersuchen, ob eine Regulation der Genexpression von IL-18BP in Nicht-Immunzellen stattfindet. Dazu wurde im ersten Schritt eine semiquantitative RT-PCR Methode etabliert, mit Hilfe derer eine schwache konstitutive Expression der IL-18BP mRNA in Zellkulturen von humanen renalen Mesangiumzellen, epithelialen DLD-1 Kolonkarzinomzellen und Fibroblasten nachgewiesen wurde. Im Folgenden konnte als wesentliches Ergebnis festgestellt werden, dass eine Induktion der Genexpression von IL-18BP durch Interferon-gamma erfolgt. Mit RNase Protection Assays wurden nach Interferon-gamma Exposition 20 – 30fache relative Steigerungen der IL-18BP mRNA detektiert. In humanen Mesangiumzellen führte außerdem bakterielles Lipopolysaccharid zum Anstieg der IL-18BP Genexpression. Im zweiten Teil der Untersuchungen ließ sich unter Verwendung eines eigens hergestellten polyklonalen Antiserums nachweisen, dass durch Interferon-gamma auch eine starke Vervielfachung der Freisetzung bzw. Sekretion von IL-18BP stattfindet. Weiterhin wurden Kokulturen von IL-12/IL18 aktivierten humanen mononukleären Zellen aus dem peripheren Blut (PBMCs) mit entweder Mesangiumzellen oder DLD-1 Zellen durchgeführt. In diesen Kokulturen bewirkte die mittels ELISA gemessene Freisetzung von endogenem Interferon-gamma durch die PBMCs ebenfalls eine Induktion der Genexpression von IL-18BP in den Mesangiumzellen und DLD-1 Zellen. Darüber hinaus wurde in anderen Experimenten untersucht, ob die Regulation von IL-18BP gleichzeitig von Änderungen im Gehalt an IL-18 begleitet wird. Während in den humanen Mesangiumzellen kein IL-18 exprimiert wurde, konnte in den DLD-1 Zellen konstitutives proIL-18 detektiert werden. Jedoch hatte Interferon-gamma in DLD-1 Zellen keinen Einfluss auf die IL-18 Expression. Die hier zusammengetragenen Resultate belegen zum ersten Mal, dass es sich bei IL-18BP nicht nur um ein konstitutiv exprimiertes Protein, sondern vielmehr um einen spezifisch regulierten Immunmodulator handelt. Die Induktion der Freisetzung von IL-18BP durch Interferon-gamma stellt den entscheidenden Schritt eines bislang unbekannten negativen Rückkopplungsmechanismus zwischen Immunzellen und ortsständigen Nicht-Immunzellen dar: Nach der Freisetzung von IL-18 bei Entzündungen, Infektionen und Tumorerkrankungen führt das von Th1-, NK- und CD8+-Zellen produzierte Interferon-gamma zu einer Sekretion von IL-18BP durch Nicht-Immunzellen. Infolgedessen kommt es konsekutiv zur Limitierung der Aktivität von IL-18 mit Reduzierung seiner proinflammatorischen Wirkungen. Da ein Übermaß an IL-18 bei der Pathogenese von chronisch entzündlichen Erkrankungen wie beispielsweise der Rheumatoiden Arthritis und dem M. Chron eine Rolle zu spielen scheint, ist von besonderem Interesse welche natürlichen Wege für die Blockierung von IL-18 existieren. Die therapeutische Applikation von IL-18BP könnte sich in Zukunft als eine neue Strategie zur erfolgreichen Behandlung dieser Krankheiten erweisen.Interleukin-18 Binding Protein (IL-18BP) is a newly described opponent of Interleukin-18 (IL-18) which neutralizes IL-18 and inhibits its biological functions by binding IL-18 with high affinity. As a pleiotropic cytokine of the immune system, IL-18 has been shown to contribute to the pathogenesis of inflammation, the protective host defense against infection as well as tumor regression. One of the major actions of IL-18 is the ability to induce the production and release of Interferon-gamma from T helper type 1 (Th1) cells, Natural Killer (NK) cells and CD8+ cytotoxic cells. IL-18BP has previously been described to be constitutively expressed and secreted. This study focuses on the regulation of IL-18BP gene expression in non-leukocytic cells. A semiquantitative RT-PCR method was established and minute constitutive levels of IL-18BP mRNA were detected in cultures of human renal mesangial cells, the colon carcinoma cell line DLD-1 and fibroblasts. More important, IL-18BP mRNA expression was strongly upregulated by Interferon-gamma. Using RNase Protection Assays 20 – 30fold relative inductions of IL-18BP mRNA levels following Interferon-gamma stimulation were observed. In cultures of human mesangial cells Lipopolysaccharide also increased IL-18BP expression. Furthermore, experiments with a new polyclonal antiserum against IL-18BP revealed that Interferon-gamma also mediates release of IL-18BP into cell culture supernatants. In addition, expression of IL-18BP was studied in cocultures of human peripheral blood mononuclear cells (PBMCs) with either human mesangial cells or DLD-1 cells. Activation of PBMCs by the combination of IL-12/IL-18 resulted in the production of endogeneous Interferon-gamma detected by ELISA and was followed by the induction of IL-18BP gene expression in mesangial cells and DLD-1 cells. Finally, in separate experiments it was excluded that the regulation of IL-18BP is accompanied by changes in IL-18 expression. Whereas no expression of IL-18 was found in human mesangial cells, proIL-18 could be detected constitutively in DLD-1 cells. However, in DLD-1 cells Interferon-gamma did not regulate IL-18 expression. This study demonstrates for the first time that IL-18BP is not only constitutively expressed but rather represents a specific regulated modulator of the immune system. Induction of the release of IL-18BP by Interferon-gamma seems to be part of a new negative feedback mechanism linking functions of immune cells and non-leukocytic cells: Release of active IL-18 during inflammation, infection and cancer is followed by production of Interferon-gamma by Th1-, NK- and CD8+-cells. Subsequently, Interferon-gamma induces secretion of IL-18BP from non-leukocytic cells, thereby limiting further IL-18 activity. Since IL-18 seems to be implicated in the pathogenesis of chronic inflammatory diseases like rheumatoid arthritis or Chron´s disease, understanding of the natural mechanisms for neutralizing this cytokine might prove to be crucial. In future, administration of IL-18BP might evolve as a new therapeutic strategy for the treatment of chronic inflammatory diseases

A LINGUAGEM DE ERICH KAESINER

A LINGUAGEM DE ERICH KAESINE