Motility of the small intestine is a result of complex neurochemical and hormonal interactions within the intestine. The net motility (contraction) of the intestine is a balance of the influences from the central nervous system, enteric nervous system and hormonal changes in the body. Recently, the discovery of several peptide neurotransmitters common to the brain and the intestine has stimulated new research into the influence of these novel neurotransmitter candidates on intestinal motility at the level of the enteric (intestinal) nervous system. The present studies examined the contractile actions of three families of peptides, the opioids, tachykinins and motilin. Each of these peptide groups has been localized in the intestine, and suggested to function in the control of intestinal motility. The peptides were administered by intraarterial injection to isolated segments of canine small intestine and the resulting contractile activity measured. The results of these experiments demonstrate that all of these peptides may elicit contractile activity of the intestine in very low doses. These actions were further examined, using pharmacological antagonists, to determine the mechanism of action and the receptor types involved in the contractile actions. The opioid peptide induced responses were found to be mediated by two receptor types, mu and delta, located on the enteric nerve and smooth muscle, respectively. Similarly, the tachykinin induced contractions were also found to be due to actions on two receptor types, SP-P and SP-K, located on the nerve and muscle layers, respectively. These data suggest that the opioids and tachykinins may have multiple functions in the intestine dependent on the site of action and the receptor type involved in the response. Administration of motilin induced long-lasting contractile patterns in the intestine. The results also suggest that the actions of motilin are mediated by intermediate neurons of the enteric plexes which synapse on terminal cholinergic motor neurons.

No description available.

No description available.

Studies have shown that gain-of- function mutant p53, AKT, and NFκB promote invasion and metastasis in tumor cells. Signals transduced by AKT and p53 are integrated via negative feedback between the two pathways. Tumor derived p53 was also indicated to induce NFκB gene expression. Due to the close relationship between p53/AKT and p53/NFκB, we hypothesized that AKT and NFκB can enhance motility in cells expressing mutant p53. Effects on cell motility were determined by scratch assays. CXCL5- chemokine is also known to induce cell motility. We hypothesized that enhanced cell motility by AKT and NFκB is mediated, in part, by CXCL5. CXCL5 expression levels in the presence and absence of inhibitors were determined by qRT-PCR. We also hypothesized that gain-of-function mutant p53 contributes to the activation of AKT. The effect of mutant p53 on AKT phosphorylation was investigated with a Ponasterone A- inducible mutant cell line (H1299/R175H) and vector control. These results indicated that AKT and NFκB enhance motility in cells expressing mutant p53 and this enhanced motility is, in part, mediated by CXCL5. However, AKT phosphorylation was independent of mutant p53.

The lymphatic system provides a conduit for the trafficking of immune cells from the periphery to draining lymph nodes, both for constitutive immune surveillance and during inflammation. Thus, leucocyte migration into the lymphatics represents an important step in the initiation of a primary immune response, which occurs within lymph nodes. Traditionally, it has been considered that neutrophils are absent from the afferent lymph, having a finite lifespan in the periphery after extravasation from the blood. However, recent research has reported the presence of neutrophils in lymph nodes, in animal models of infection, where neutrophil trafficking was found to occur through afferent lymphatic vessels. This thesis examines the mechanisms regulating neutrophil migration, both by the lymphatic endothelium and neutrophils themselves, under resting and inflammatory conditions. Primary human dermal lymphatic endothelial cells (HDLECs) respond to the pro- inflammatory cytokine, TNF-α by instigating a distinct expression programme, characterised by the up-regulation of various adhesion molecules (ICAM-1, VCAM-1, E-selectin), and CXC- chemokines (ENA-78, GROβ, IL-8), as well as other potential regulators of neutrophil entry such as constitutively expressed adhesion molecules, CD99 and ESAM. Moreover, neutrophils possess counter-receptors for these adhesion molecules and contain basement membrane-specific proteases (elastase) and matrix metalloproteinases (MMPs) such as MMPs -8 and -9, localised in intracellular granules, ready to be exocytosed upon inflammatory stimuli. In vitro data presented in this thesis demonstrate that neutrophil adhesion and transmigration of the lymphatic endothelium is entirely dependent on prior activation of the monolayer with TNF-a. Furthermore, the aforementioned lymphatic-expressed adhesion molecules and chemokines, as well as neutrophil-derived proteases and MMPs are shown to play critical roles in neutrophil adhesion and transmigration of the lymphatic endothelium. Subsequent in vivo experiments confirmed that neutrophil trafficking to lymph nodes across lymphatic vessels is wholly dependent on prior vaccination with Mycobacterium bovis Bacillus Calmette-Guerin (BCG) Tokyo-172. Moreover, neutrophils trafficking to lymph nodes across lymphatic vessels are shown to require ICAM-1. The results described in this thesis provide the first evidence that both the lymphatic endothelium and neutrophils act in concert to regulate entry to lymph nodes and determine the outcome of infection, or vaccination.

Introduction: Our knowledge of normal human colonic motility remains incomplete. Historically, this has been due to the relative inaccessibility of this organ for study, and the lack of standardisation of methods used to investigate it. Recent device development has provided us with advanced tools by which to assess colonic motility, namely pancolonic manometry, and the wireless motility capsule (WMC). Using traditional diagnostic tests, a subgroup of patients presenting with severe intractable symptoms, but without organic disease, are found to have slow transit constipation (STC). This is believed to be primarily due to colonic dysmotility, although colonic motor functions remain poorly understood in this group also. Aims: The principal aims of this thesis were to: (1) explore the effect of pancolonic manometric recording technique on colonic motility; (2) describe pancolonic motility in STC, compared to healthy control subjects; (3) using the wireless motility capsule (WMC), validate the precise location of the pH fall around the ileo-caecal junction as a landmark for measuring colonic motility; (4) obtain normative data for colonic motility (transit and contractility) and intraluminal pH in a large cohort of healthy volunteers using the WMC, and compare this to patients with STC. Methods: The following methods were used: (1) prolonged pancolonic manometry in healthy volunteers and patients with STC; (2) a dual scintigraphic technique, involving radioactive-labelling of the WMC in healthy volunteers; (3) wireless motility capsule studies of colonic motility in healthy volunteers and in patients with STC. Results: Colonic manometric recording technique (bowel preparation or not, and different catheter types) significantly influences some characteristics of propagating sequence (PS) activity, including frequency, amplitude, polarity, relationship between consecutive PSs, and circadian rhythm. Patients with STC display dysregulated colonic motor function represented by disorganised spatiotemporal patterning and loss of 'regional linkage' among PSs. The fall in pH measured by the WMC was confirmed to be either in the caecum, ascending colon, or as the capsule moved from the caecum to the ascending colon. Using the WMC, the upper limit of normal colonic transit time (CTT) was found to be 51 h; however, CTT is not a continuous variable and exhibits peaks every 24 h. CTT is significantly prolonged in females and affected by the study protocol employed. In patients with STC, colonic contractility (motility index) is increased in comparison with healthy controls, and intraluminal pH is more acidic in the proximal colon, and more alkaline in the distal colon. Conclusions: The method of pancolonic manometry requires standardisation. However, novel metrics derived from prolonged pancolonic recordings have improved our understanding of the physiology of colonic motor function in health, and also pathophysiology in constipation. The WMC provides an alternative, less invasive method to investigate colonic motility; this technique also requires standardisation, but early results in patients with STC complement those from manometry, and also reveal alterations in intraluminal pH that may be of pathophysiological significance.

by So Siu Cheung, Eddie. / "September 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Philosophiae Doctor - PhD / In the marine environment, penguins have been described as curators and serve a critical role in ecological balance. The African penguin (Spheniscus demersus) has undergone a rapid population decline, mainly due to disturbances in their natural habitat. The African penguin was up-listed from vulnerable to endangered on the IUCN Red List for Threatened Species in 2010 and thus urgent conservation action is required. Integral to long-term conservation action of any species is a basic knowledge of its reproductive biology, which is currently lacking for African penguins. The main aim of this investigation was to evaluate techniques for the collection of semen in African penguin and to determine sperm quality in order to cryopreserve sperm for in vitro fertilization (IVF) purposes of captive and wild populations. Semen was collected once a week during two breeding seasons from two captive African penguins. Ejaculates (n=51) were obtained over two breeding seasons (Jan-Feb and Jun-Oct) and evaluated for semen volume, sperm concentration, sperm vitality, sperm motility and sperm morphology. In addition twelve (six females and six males, n=4 were breeding pairs) captive African penguins were monitored for hormone (estradiol, testosterone, progesterone) levels prior to and after the egg-laying period.

The basement membrane protein laminin-332 (laminin-5) mediates both stable cell adhesion and rapid cell migration, and thus has the potential to either restrain or promote tumor cell metastasis. The major cellular receptors for laminin-332 are integrin α3β1, which mediates rapid tumor cell migration, and integrin α6β4, which often mediates stable cell attachment. Tetraspanin protein CD151 interacts directly with both α3β1 and α6β4 integrins and with other tetraspanins, thereby promoting α3β1 and α6β4 association with tetraspanin-enriched microdomains on the cell surface. To explore the possibility of selectively modulating tumor cell responses to laminin-332, we re-expressed a series of CD151 mutants in epidermoid carcinoma cells with near total, RNAi- mediated silencing of endogenous CD151. CD151's interactions with its integrin partners or its interactions with other tetraspanins were selectively disrupted by specific mutations in the CD151 large extracellular loop (EC2 domain) or in intracellular CD151 palmitoylation sites, respectively. CD151- integrin association and CD151-tetraspanin association were both important for α3β1 integrin- dependent initial adhesion and rapid migration on laminin-332. Remarkably, however, only CD151-integrin association was required for stable, α6β4 integrin-dependent cell attachment on laminin-332. In gap-filling assays, where CD151-silenced cells moved more rapidly than WT cells, again, only CD151-integrin association was required to restrict movement into the gap, suggesting that both α3β1 and α6β4 integrin must be able to associate with CD151 in order restrict group motility. In addition, we found that a QRD amino acid motif in the CD151 EC2 domain that had been thought to be crucial for CD151-integrin interaction is not essential for CD151-integrin association or for CD151's ability to promote several different integrin functions. These new data suggest potential strategies for selectively modulating migratory cell responses to laminin-332, while leaving stable cell attachment on laminin-332 intact.

Bibliography: leaves 159-192. / viii, 192 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines aspects of the control and measurement of pyloric motor function believed to be relevant to the role(s) of the pylorus in the regulation of normal gastric emptying. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 1992