Hepatocyte transplantation : experimental and clinical studies

Hepatocyte transplantation is an experimental treatment for patients with end-stage liver disease and inborn metabolic liver disorders. Studies in animal models and human trials have shown that allogenic hepatocytes infused through the portal vein physiologically integrate into the liver parenchyma, replacing missing liver function. Current research data provide a proof of principle for clinical hepatocyte transplantation in a wide range of liver diseases. However, most patients ultimately undergo whole organ liver transplantation due to insufficient graft function. Thus, the efficacy and long-term results of clinical hepatocyte transplantation must be improved before this treatment can be introduced into routine clinical care. The present thesis summarizes experimental and clinical studies with the general aim of identifying current limitations and improving outcomes of hepatocyte transplantation. Paper I investigates strategies for improving short-term preservation of isolated human hepatocytes. Human hepatocytes are usually cold stored for prolonged periods between isolation and infusion. We found that isolated human hepatocytes undergo cell death and lose hepatocyte-specific function during this cold storage period. An alternative technique of liver tissue storage and repeated isolations led to improved viability and function of isolated hepatocytes before infusion. In Papers II and III, a hepatocyte transplantation model was established in the ApoE knockout mouse. Clinically relevant animal models are necessary for developing new treatment strategies. The ApoE knockout mouse is an ideal model of an inherited metabolic liver disease. ApoE is mainly produced by hepatocytes and its deficiency results in extrahepatic disease. ApoE (−/−) mice display severe hypercholesterolemia leading to premature atherosclerosis. We observed that transplanted wild-type hepatocytes integrated into the liver and excreted ApoE, and that this serum ApoE correlated with hepatic donor cell engraftment. Transplantation without preconditioning treatment resulted in serum ApoE levels of 1–2% of wild-type levels, which did not affect hypercholesterolemia. However, pretreatment with retrorsine gave donor hepatocytes a growth advantage, resulting in progressive repopulation of up to 55% of the recipient liver. This increased repopulation by donor hepatocytes led to normalization of hypercholesterolemia and prevention of atherosclerosis. Paper IV evaluated the safety and efficacy of partial hepatectomy preconditioning with hepatocyte transplantation in two patients with Crigler-Najjar syndrome type I. Partial hepatectomy in combination with hepatocyte transplantation was safe and induced a regenerative response. Serum bilirubin decreased to approximately 50% of pretransplant concentrations, and allograft function was further confirmed by detection of bilirubin diglucuronides in bile after transplantation. However, both patients lost graft function in association with the emergence of donor-specific HLA antibodies

Simple Model for Cathode Coupling Voltage Versus Background Pressure in a Hall Thruster

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143041/1/6.2017-4889.pd

A Case of Juvenile Papillomatosis, Aka “Swiss Cheese Disease”

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98810/1/tbj12137.pd

Expanded Thruster Mass Model Incorporating Nested Hall Thrusters

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143089/1/6.2017-4729.pd

High Power Demonstration of a 100 kW Nested Hall Thruster System

The XR-100 team successfully completed high power system testing of a Nested Hall Thruster system made up of the X3 Nested Hall Thruster, a modular Power Processing Unit, and a 5 valve Mass Flow Controller as the culmination of work performed under a NASA NextSTEP program. The test campaign attained several key firsts, including highest directly measured thrust of an electric propulsion (EP) string, highest demonstrated current of an EP string, and highest power operation of an EP string at thermal equilibrium published to date. Most importantly, the XR-100 system testing demonstrated that a 100 kW-class Nested Hall Thruster system has comparable performance and behavior to current state-of-the-art mid power Hall Thrusters, validating that the heritage technology can be scaled up to 100+ k

Past Futures and the Rise of the Flexibilisation Imperative

Flexibility has developed into an important condition of society today and is often perceived as reaction to challenging social circumstances. But how and why did flexibility became so powerful on both the societal and individual level? And how, if the focus is on biographies, is it linked to education? In this nexus, education and institutionalised educational processes build a hinge between society and the individual. To find educational solutions to meet the challenge of the change in societies’ constitution, the future is addressed. This is particularly true for vocational education and training (VET), since VET is supposed to prepare for the working world of tomorrow and thus already has the anticipation of the future in its mandate. However, futures are always speculative and plural in many respects. Therefore, futures coexist or compete for validity and thereby exclude each other. Against this backdrop, the general research interest lies in the genesis of the contemporary, flexible human constitution and the influence of VET on its evolvement. The the question will be examined, as to how the flexibilisation of humans was discussed within future configurations of politicians and in the VET law since its establishment in 1930

Extranodal Rosai–Dorfman Disease of the Breast

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135227/1/tbj12690.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135227/2/tbj12690_am.pd

Cross Domain Privacy Protection for Location-Based Services

This paper investigates the current status of Information System Security (ISS) within New South Wales State government agencies in Australia. A 3-year longitudinal survey was used to increase awareness and motivate ISS managers. In addition, the survey was used as a management tool to monitor compliance with ISS standard’s controls (AS/NZS17799:2001). In 2004 an amendment to the standard added critical success factors (CSFs) as being necessary for an agency’s movement to accreditation. An analysis of the CSFs results was undertaken to determine the status of an independently acting agency’s security readiness and they were summarized to then provide an overall measure. This measure provided a ‘benchmark’ for an agency’s security readiness to the standard’s CSFs (AS/NZS17799:2004.AMDT). While the process for improving security based on CSFs is adequate, actual improvement in ISS across government requires further effort. This research contributes to the level of understanding of ISS compliance within e-Government

Laser Measurement of Anomalous Electron Diffusion in a Crossed-Field Plasma

Non-classical electron diffusion in crossed-field, low-temperature plasmas is measured experimentally. Laser-induced fluorescence and Thomson scattering are used to determine the inverse Hall parameter, a metric for cross-field transport, in a Hall ion source. The measured diffusion is found to depart from fluid model results at the peak electric field, remaining constant instead of exhibiting a sharp transport barrier. The implications of this result are discussed in terms of the current understanding of non-classical diffusion in low-temperature plasmas.Comment: 4 figure

Occult fallopian tube carcinoma detected in routine pelvic washing specimens submitted for staging: Another justification for pelvic washing cytology?

Peritoneal washing cytology is important in the staging, prognosis, and treatment schema for women diagnosed with gynecologic malignancies. Additionally, peritoneal washings are often performed before the specific diagnosis or even the distinction between benign or malignant lesion is known. Occasionally, the cytology and surgical pathology specimens, although obtained during the same procedure, will show unexpected and/or discordant findings. Perhaps, the greatest dilemma occurs when atypical cells suggestive of malignancy are identified in peritoneal washing specimens when a corresponding benign or discordantly low grade malignant diagnosis is made in the surgical pathology specimen. We present two such cases in which further investigation proved extremely valuable, not only leading to resolution of initially discrepant cytologic and surgical pathology findings but also in the process leading to second diagnoses of early fallopian tube carcinoma. Increasing evidence appears to be pointing to the fallopian tube as the site of origin of many serous carcinomas previously thought to be of primary pelvic or ovarian origin. These cases further confirm the utility of peritoneal washing cytology as a diagnostic modality when routine gross examination and sampling of the surgical specimens alone would have failed to provide the complete diagnosis. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64442/1/21129_ftp.pd