Thesis (M.D.)--University of Maryland, 1815. / Microform version available in the Readex Early American Imprints series.

Thesis (M.Med.Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 75-107). Also available in print.

Thesis (doctoral)--Freie Universität Berlin, 1980.

Thesis (Ph.D.)--University of Melbourne, Dept. of Medicine, (Royal Melbourne Hospital / Western Hospital), Faculty of Medicine, Dentistry and Health Sciences, 2010. / Typescript. Includes bibliographical references (p. 230-243)

Murine hepatitis virus type 3 (MHV-3), a member of the coronavirus family, induces a response that varies with the age and genetic background of the host mouse strain. A/J mice are fully resistant to the virus, while Balbc/J are fully susceptible and C3HebFe/J are semi-susceptible, making it possible to predictably reproduce the major human responses to hepatitis viruses. Although there has been considerable discussion of viral pathology in the literature, there has been much less emphasis on pathogenesis. In the experiments described here, histological, biophysical, and immunological techniques have been used to define the processes and cells involved. Transmission electron microscopic observations have confirmed that Kupffer and endothelial cells of hepatic sinusoids show clear changes by 12 hrs post-infection (p.i.), which are more advanced than hepatocellular changes. No replicating virus was seen in altered hepatocytes up to 3 days p.i. Scanning electron microscopy demonstrated that areas of necrosis are focal in nature and at 2-3 days p.i. consist of small spherical areas without flow. In vivo microcirculatory studies confirm the localized nature of the lesion and have shown that red cell velocity can be recorded in individual sinusoids . Velocities were found to vary from zero within a lesion to a normal velocity of 69±31 um/sec over a distance of not more than 3 sinusoids. In-vivo microcirculatory studies also revealed the ability of macrophages to move upstream (against flow) in the hepatic sinusoids. Using fluorescein labelled antibodies to cell surface markers (Thy-1, Lyt-2, and L3T4) it was shown that no T-cells of any subset were present in the areas of hepatocellular necrosis. Furthermore, treatment with cyclosporine A, which would be expected to decrease necrosis due to cell mediated cytotoxicity, did not significantly alter the course of the disease. The only cells which increased in number in the liver post infection were cells of the monocyte/macrophage lineage (Mac 1+), which had increased twofold at 12 hrs (p<.025) p.i. and to greater than twenty fold (p<.005) by 3 days p.i. Resistance in the A/J strain did not reflect an inability of the immunocompetent cells to present and respond to viral antigen. It was demonstrated that MHV-3 infected macrophages from resistant A/J mice are better able to stimulate proliferation of allogeneic and syngeneic lymphocytes than those from the sensitive Balb/cJ strain. In contrast, MHV-3 infection caused a significant enhancement of chemiluminescence from Balb/cJ macrophages, which did not occur in A/J animals. In vivo studies demonstrated a significant increase in free radical reaction products, including conjugated dienes (of long chain free fatty acids and aldehydes), thiobarbituric acid reactive substances, and lipid soluble fluorescent products between 12-72 hours p.i. with MHV-3 in the livers of susceptible Balb/cJ strain mice. All of these are products of oxidative cleavage of cellular and membrane polyunsaturated fatty acids, and result from the action of oxygen free radicals. Free radical inhibitors, or quenchers of free radical reaction products, were able to significantly reduce the liver necrosis in the susceptible mouse strain following infection. Radioimmune assays for antibody to MHV-3 have confirmed the presence of preformed antibodies to (or cross-reactive with) MHV-3 in the sera of both susceptible and resistant mice, pre and post-infection. Immunofluorescent labelled antibodies have also been used to demonstrate the presence of IgG deposits in the sinusoids of the liver both pre and post infection. This suggests the possibility that these mice have been infected with a non-virulent MHV strain prior to these experiments. From these studies, we conclude that the hepatic injury caused by MHV-3 infction in Balb/cJ mice is mediated predominantly by fixed and migratory cells of the mononuclear phagocytic series. Susceptibility and resistance are related to strain dependant differences in the response of macrophages (and Kupffer cells) to infection, and include the release of procoagulant activity (previously shown) and reactive oxygen radicals (and possibly other macrophage activation products such as PAF) that act together to induce hepatocellular necrosis. Preformed non-neutralizing antibody and an intact complement cascade may enhance viral uptake and activation of macrophages in the Balbc/J mice. Resistance to necrosis may be enhanced by a genetic deficiency of C5 in the A/J mice, preventing the formation of the membrane attack complex and hence complement dependant cell lysis, or macrophage activation. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Hepatitis C Virus (HCV) is the most common blood borne infection in the United States and frequently develops into a chronic disease, which can lead to serious health complications including liver damage, cirrhosis, cancer, and death. Due to vague symptomology associated with HCV, half of people with chronic HCV are unaware of their condition. New HCV infections are most common in persons who inject drugs (PWID) and chronic infection is currently most prevalent in baby boomers (birth age 1945 to 1965). The purpose of this project was to increase health care professionals? comfort level and knowledge regarding HCV screening guidelines per USPSTF as well as to improve HCV screening rates for the PWID cohort and baby boomer cohort. This project was implemented when risk-based HCV screening was recommended. Many eligible patients do not undergo screening as nationally screening rates are low at 12.8%. Lack of time and knowledge deficit are common documented barriers that health care professionals identified throughout the literature that negate screening uptake. This project was implemented by a multidisciplinary team utilizing the PDSA method. Two one-hour educational sessions were developed and provided to all health care professionals at two federally qualified health center primary care clinics in the Midwest region. The presentations were conducted by an infectious disease physician, a pharmacist who specializes in viral hepatitis, and the co-investigator in October 2019. Academic detailing occurred to follow-up and support health care professionals. A voluntary, post-implementation survey was distributed to participants after the educational sessions and an abbreviated survey two months later. PWID and baby boomer and pre- and post-implementation screening rates were computed through the facility?s established process. After this project, HCV screening rates increased by 16% for the baby boomer cohort and 5.5% for the PWID cohort. Health care professionals? knowledge and confidence in HCV screening guidelines was enhanced through this intervention. With new updated universal HCV screening guidelines, continued efforts to screen for HCV is essential.

Tang Yuk Kwan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 130-144). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.iv / List of Abbreviations --- p.v / List of Figures --- p.ix / List of Tables --- p.xii / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Hepatitis B Virus (HBV) --- p.1 / Chapter 1.1.1 --- Epidemiology --- p.1 / Chapter 1.1.2 --- History of HBV --- p.2 / Chapter 1.1.3 --- Hepatitis B in Hong Kong --- p.3 / Chapter 1.2 --- Virology --- p.4 / Chapter 1.2.1 --- Hepadnavirus Family --- p.4 / Chapter 1.2.2 --- HBV Particles Types --- p.4 / Chapter 1.2.3 --- HBV Genome --- p.6 / Chapter 1.2.4 --- HBV Life Cycle --- p.8 / Chapter 1.2.5 --- Hepatitis B Surface Antigen --- p.14 / Chapter 1.3 --- HBV Immunobiology During Viral Infection --- p.17 / Chapter 1.3.1 --- Acute Hepatitis B Virus Infection --- p.19 / Chapter 1.3.2 --- Chronic Hepatitis B Virus Infection --- p.23 / Chapter 1.3.3 --- Cytokines in Suppression of HBV Infection --- p.23 / Chapter 1.3.4 --- The mechanism of HBV Persistence --- p.26 / Chapter 1.4 --- HBV Therapy --- p.28 / Chapter 1.4.1 --- Interferon alpha (IFN-α) --- p.29 / Chapter 1.4.2 --- Lamivudine --- p.31 / Chapter 1.5 --- Phyllanthus --- p.32 / Chapter 1.5.1 --- In vitro study --- p.32 / Chapter 1.5.2 --- In vivo study --- p.33 / Chapter 1.5.3 --- Clinical Trials --- p.34 / Chapter 1.5.4 --- Anti-tumor Effect of P. amarus --- p.35 / Chapter 1.5.5 --- Active component(s) of P. am arus --- p.35 / Chapter 1.6 --- Alexander cells --- p.37 / Chapter 1.7 --- Objectives --- p.38 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1 --- Materials --- p.39 / Chapter 2.1.1 --- Phyllanthus urinaria --- p.39 / Chapter 2.2 --- In vitro study --- p.39 / Chapter 2.2.1 --- Materials --- p.39 / Chapter 2.2.1.1 --- Cell Lines --- p.39 / Chapter 2.2.2 --- Reagents and Buffers --- p.40 / Chapter 2.2.2.1 --- Phosphate Buffered Saline (PBS) --- p.40 / Chapter 2.2.2.2 --- Reagents and Buffers for mRNA Genes Expression Analyses --- p.40 / Chapter 2.2.2.3 --- Reagents and Buffers for Protein Analyses --- p.41 / Chapter 2.2.2.4 --- Reagents for Purification of Splenocytes --- p.43 / Chapter 2.2.3 --- Methods --- p.43 / Chapter 2.2.3.1 --- MTT Assay --- p.43 / Chapter 2.2.3.2 --- IMX Assay --- p.43 / Chapter 2.2.3.3 --- Semi-quantitative RT-PCR --- p.44 / Chapter 2.2.3.3.1 --- Extraction of RNA --- p.44 / Chapter 2.2.3.3.2 --- Reverse Transcription Polymerase Chain Reaction (RT-PCR) --- p.45 / Chapter 2.2.3.3.3 --- Polymerase Chain Reaction (PCR) --- p.46 / Chapter 2.2.3.4 --- Protein Analysis --- p.48 / Chapter 2.2.3.4.1 --- Extraction of Protein --- p.48 / Chapter 2.2.3.4.2 --- Determination of Protein Concentrations --- p.48 / Chapter 2.2.3.4.3 --- Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.49 / Chapter 2.2.3.4.4 --- Electroblotting of Protein --- p.50 / Chapter 2.2.3.4.5 --- Immunoblotting of Protein --- p.50 / Chapter 2.2.3.4.6 --- Enhanced Chemiluminescence (ECL) Assay --- p.51 / Chapter 2.2.3.5 --- Assay of preSl Promoter Activity --- p.51 / Chapter 2.2.3.5.1 --- Cloning of preSl Promoter from HBV Genome --- p.51 / Chapter 2.2.3.5.2 --- Transfection --- p.52 / Chapter 2.2.3.5.3 --- Luciferase Assay --- p.53 / Chapter 2.2.3.6 --- Pilot Experiments for the Investigation of Immunostimulatory Effect of (aq) P. urinaria --- p.53 / Chapter 2.2.3.6.1 --- Purification of Splenocytes --- p.53 / Chapter 2.2.3.6.2 --- Cytotoxicity Assay of Splenocytes --- p.54 / Chapter 2.2.3.6.3 --- [3Hl-thymidine Uptake Assay --- p.54 / Chapter 2.2.3.6.4 --- Purification of Macrophages --- p.55 / Chapter 2.3 --- In vivo Assay --- p.56 / Chapter 2.3.1 --- Materials --- p.56 / Chapter 2.3.1.1 --- Balb/c Mice --- p.56 / Chapter 2.3.1.2 --- Reagents for Cytokine Assay --- p.56 / Chapter 2.3.1.3 --- Reagents for Flow Cytometric Analysis of T Cell Subpopulations --- p.57 / Chapter 2.3.2 --- Methods --- p.57 / Chapter 2.3.2.1 --- Purification of Splenocytes --- p.57 / Chapter 2.3.2.2 --- Enzyme Assay --- p.57 / Chapter 2.3.2.3 --- Flow Cytometric Analysis of T Cell Subpopulations --- p.59 / Chapter 2.3.2.4 --- Cytokine Assays --- p.60 / Chapter 2.4 --- Statistical Analysis --- p.63 / Chapter Chapter 3 --- Results / Chapter 3.1 --- In vitro Assays --- p.64 / Chapter 3.1.1 --- Study of the Cytotoxicity of Crude Extract of (aq) P. urinaria on Alexander Cells by the MTT Assay --- p.64 / Chapter 3.1.2 --- Study of the Cytotoxicity of Crude Extract of (aq) P. urinaria on WRL 68 Cells by the MTT Assay --- p.66 / Chapter 3.1.3 --- Study of the Cytotoxicity of Crude Extract of (aq) P. urinaria on Primary Mouse Macrophages by the MTT Assay --- p.67 / Chapter 3.1.4 --- Effect on HBsAg Secretion by the IMX Assay --- p.69 / Chapter 3.1.5 --- Effect of Viral Gene Expression by Semi-quantitative RT-PCR --- p.73 / Chapter 3.1.6 --- Effect of Intracellular Viral Proteins Expression by Western Blotting Analyses --- p.75 / Chapter 3.1.7 --- preSl Promoter Activity in Alexander Cell Line and Hep3B Cell Line --- p.77 / Chapter 3.1.8 --- Effect of (aq) P. urinaria on preSl Promoter Activity in Hep3B Cell Line --- p.80 / Chapter 3.1.9 --- Pilot Experiments for the Investigation of Immunomodulatory Effect of (aq) P. urinaria --- p.82 / Chapter 3.1.10 --- Study of the Cytotoxicity of Crude Extract of (aq) P. urinaria on Primary Splenocytes by the MTT Assay --- p.85 / Chapter 3.2 --- In vivo Assay --- p.88 / Chapter 3.2.1 --- Study of the Immunomodulatory Effect of the Crude Extract of (aq) P. urinaria on Normal Balb/c Mice by [3H]-thymidine Uptake Assay --- p.88 / Chapter 3.2.2 --- Study of the Toxicity of Crude Extract of (aq) P. urinaria on Heart and Liver of Normal Balb/c Mice by Enzyme Assay --- p.91 / Chapter 3.2.3 --- Flow Cytometric Analysis of T Cell Subpopulations --- p.94 / Chapter 3.2.4 --- Analysis of Stimulatory Effect on Four Different Cytokines by ELISA --- p.100 / Chapter Chapter 4 --- Discussion / Chapter 4.1 --- In vitro Assay --- p.110 / Chapter 4.2 --- In vivo Assay --- p.116 / Chapter 4.3 --- Conclusions --- p.127 / Chapter 4.4 --- Future Prospects --- p.129 / References --- p.130

Thesis (MPH))University of Limpopo (Medunsa Campus), 2011. / Introduction: Hepatitis B virus (HBV) is a highly infectious virus responsible for considerable morbidity and mortality world wide. Chronic HBV carriers can transmit HBV parenterally in a hospital setting putting healthcare workers (HCWs) and their patients at risk of infection. Aim and objectives: This study aimed to investigate knowledge, attitudes and practices towards prevention and control of HBV amongst nurses, doctors and laboratory personnel. Objectives were to determine: (a) the knowledge; (b) the attitudes; (c) the practices of nurses, doctors and laboratory personnel; (d) if there are any associations between (1) knowledge and practice, and (2) attitudes and practice; (e) the predictors of HBV vaccination uptake. Materials and Methods: This was a cross-sectional descriptive study. Self-administered questionnaires were distributed to doctors, laboratory staff and nurses at Princess Marina Hospital. Results: Two hundred questionnaires were distributed and a total of 117 were returned, giving an overall response rate of 58.5%. More doctors had good knowledge (38.9% [7/18]), followed by 20% (4/20) of laboratory staff and 11.4% (9/79) of nurses. Most staff (100% [20/20] of laboratory staff; 97.5% [77/79] of nurses; 94.4% [17/18] of doctors) had positive attitudes. More laboratory staff (100 [20/20]) displayed good practices, followed by nurses (94.9% [75/79]); and lastly doctors (88.9% [16/18]). There were no significant associations between knowledge or attitudes and practices. Vaccination was inadequate, with 50.9% (59/116) of HCWs having received at least one dose, and of these only 61% (36/59) receiving all 3 doses. Needle stick injuries occurred in 31.6% (37/117), while 33.9% (39/115) reported blood or body fluid splashes. None of the HCWs accessed PEP after exposure. Being a laboratory worker (OR: 148.4) or doctor (OR: 125.7) were the only predictors of vaccination uptake. Conclusion: There is need to increase knowledge of HCWs, vaccination availability, vaccination uptake, PEP, and reduce the exposures of HCWs.

This thesis investigated how virologic and serologic kinetics of the hepatitis B virus (HBV) could influence the natural history and treatment of chronic hepatitis B (CHB). Virologic kinetics were described in the first five studies, with serologic kinetics being described in the next five. The first study delineated the HBV DNA profiles of 1,400 treatment-naive Asian CHB patients. Increasing viremia was noted with increasing age, highlighting the large therapeutic demand in Asian patients with hepatitis B e antigen (HBeAg)-negative CHB. The second study analyzed the association between viral load and liver histology in 319 patients, showing HBV DNA levels to have strong association with HBeAg-negative disease severity. The next three studies investigated the efficacy of baseline and on-treatment HBV DNA levels in predicting clinical outcomes in 117, 165 and 222 patients on telbivudine, lamivudine plus adefovir and entecavir respectively. Absolute on-treatment HBV DNA levels at week 12 or 24 predicted favorable outcome with telbivudine and lamivudine / adefovir therapy, while excellent viremic suppression with very low rate of resistance development was shown in the entecavir study. The following three studies examined the role of serum HBsAg measurements in different disease phases of CHB. First, histology specimens of 140 HBeAg-positive patients were analyzed together with HBsAg levels. High HBsAg titers (>25,000 IU/mL) were found to be predictive of insignificant fibrosis. In the next study involving 300 treatment-naive HBeAg-negative patients stratified by their viral loads, combination of low HBsAg and HBV DNA levels predicted significant HBsAg decline. This is followed by a study comparing HBsAg levels of 203 CHB patients achieving HBsAg seroclearance with 203 age- and sex-matched controls over a 3-year period. Serum HBsAg <200 IU/mL and a significant annual HBsAg reduction were found to be predictive of HBsAg seroclearance. The penultimate study investigated the usage of two novel HBV serologic markers, linearized HBsAg and hepatitis B core-related antigen, in 329 CHB patients achieving HBsAg seroclearance with a conventional HBsAg assay. More than 40% of patients had seropositivity to one or both serologic tests. Finally, the last study of this thesis investigated and compared the changes in serum HBsAg, intrahepatic HBV DNA and covalently closed circular DNA (cccDNA) after 1 year of nucleoside analogue therapy. Minimal changes in both serum HBsAg and intrahepatic cccDNA were noted after 1 year of therapy, but in patients with a significant decline in serum HBsAg levels, there was a corresponding significant reduction in cccDNA. This series of studies illustrated how the monitoring of serum HBV DNA and HBsAg levels could assist in optimizing management strategies for CHB. / published_or_final_version / Medicine / Master / Doctor of Medicine

Thesis (M. Med. Sc.)--University of Hong Kong, 2010. / Includes bibliographical references (p. 51-58).