The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on December 29, 2009). Thesis advisor: Dr. Matthew C. Lucy and Rodney D. Geisert. Vita. Includes bibliographical references.

Zugl.: Berlin, Freie Univ., Diss., 2008

No description available.

Carcinoma growth requires a supportive tumor stroma. The concept of reciprocal interactions between tumor and stromal cells has become widely acknowledged and the connective tissue activation seen in the malignant process has been likened to that of a healing wound. Little is, however, known about the specific characteristics of these interactions, distinguishing them from the interplay occurring between epithelial and stromal cells in wound healing. In order to study differences in the humoral effects of malignant and benign epithelial cells on fibroblasts, we used an in vitro coculture model with human oral squamous cell carcinoma cells (SCC) or normal oral keratinocytes (NOK) on one side of a semi-permeable membrane and fibroblasts seeded in gels on the other. Pro-collagens α1(I) and α1(III) were more downregulated in NOK cocultures compared to SCC cocultures. IL-1α was identified as a major keratinocyte-derived soluble factor behind the effects observed. We concluded that SCC are less antifibrotic compared to NOK. There was also a differential expression among enzymes involved in ECM turnover. The urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) were both upregulated by NOK, but not by SCC. Here, rIL-1ra caused further upregulation of PAI-1. Global gene expression in fibroblasts was assessed using Affymetrix™ arrays. In total, 82 transcripts were considered differentially expressed; 52 were up- and 30 were downregulated in SCC compared to NOK cocultures. Among the differentially expressed genes there was an enrichment of genes related to collagens and to a nonspecific, innate-type response. The innate response marker pentraxin (PTX3) was upregulated by keratinocyte-derrived IL-1α in both NOK and SCC cocultures. We observed a considerably higher IL-1α / IL-1ra quotient in SCC cocultures, however, while PTX3 mRNA upregulation was higher in SCC cocultures, there was no difference in the level of PTX3 secreted protein. Taken together, we concluded that NOK and SCC regulate genes important for ECM composition and for the innate immune-response differentially. IL-1α was identified as one important mediator of the observed effects. In general, SCC appeared to be more profibrotic in their effects on fibroblasts.

The objective of this study was to investigate the effect of recombinant human interleukin-1beta (rHIL-1beta) and interleukin-8 (rHIL-8) on bovine neutrophil migration and degranulation. An in vitro co-culture system was used to study bovine neutrophil migration. This simulative system allowed studying neutrophil migration across endothelium (bovine aorta endothelial cells), extracellular matrix (ECM), and epithelium (MAC-T) in the correct sequences and directions. Quantification of neutrophil migration was carried out by assaying the activity of myeloperoxidase, a major enzyme of neutrophils. Degranulation of azurophilic, specific, and tertiary granules was studied by measuring releases of myeloperoxidase, lactoferrin, and gelatinase, respectively. The results showed that bovine neutrophils were able to migrate across the simulative co-culture system in response to zymosan activated serum. Recombinant HIL-8 was demonstrated to have a dose-dependent effect on bovine neutrophil migration. Furthermore, rHIL-8 had a dose-dependent effect directly on degranulation of azurophilic and specific granules, but not on tertiary granules. On the other hand, rHIL-1beta only had a significant effect on degranulation of azurophilic granules when the concentration of 100 ng/ml was used. The dose effect of rHIL-1beta on specific degranulation was much stronger. Moreover, the effect of 100 ng/ml rHIL-1beta was augmented when the rHIL-1beta containing solution was preincubated with MAC-T monolayers for four hours. This indicated that MAC-T cells might generate other degranulating factors in response to the stimulation of rHIL-1beta. These MAC-T-derived degranulating factors did not have effect on the release of tertiary granule contents.

Immunological stressors, in the form of clinical and sub-clinical disease are currently controlled using both prophylactic antibiotics in-feed, and therapeutic antibiotic treatment. Respiratory disease, primarily Actinobacillus pleuropneumoniae (App) infection, is recognised as a major factor causing reduced productivity in pigs. This thesis reports investigations into the use of novel immunomodulators in particular Interleukin 4 (IL-4) and Interleukin 1 receptor antagonist (IL-1ra) as alternatives to antibiotics to treat App infection. Immunological and molecular biological assays were used to investigate and accumulate data. An in vitro study undertaken to find potential anti-inflammatory substances, revealed that Interleukin 8 (IL-8) mRNA production stimulated by PMA or LPS in whole pigs' blood was suppressed by IL-4. IL-1ra also suppressed stimulated IL-8 mRNA production by heat killed App bacteria (KB) in vitro. An acute LPS challenge in pigs in vivo however, showed no variation in illness or weight loss between pigs treated prophylactically with anti-inflammatory substance (IL-4 and IL-1ra) and saline treated pigs. The use of plasmids as a delivery system for anti-inflammatory substance did not show promise since it did not enhance growth or prolong the expression of the substances in the pigs. However, in the chronic App challenge model IL-4 and IL-1ra administered prophylactically in vivo showed an ability to improve growth. The therapeutic administration of IL-4 and IL-1ra to App challenged pigs showed no difference in pigs' growth, regardless of the treatment or control administered. To conclude, IL-4 and IL-1ra showed promise when administered prophylactically and improved growth and abrogated disease under conditions of App challenge. However when IL-4 and IL-1ra where administered therapeutically they did not perform as well. Moreover these compounds have potential as a commercial application to reduce the growth reduction caused by disease such as App.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Beyin Cerrahi Anabilim Dalı, 2007. / Bibliyografya var.

Thesis (M.S.)--University of Missouri--Columbia, 2004. / "July 2004." Typescript. Includes bibliographical references (leaves 63-70). Also issued on the Internet. Also available on the Internet.