Biomedical subjects

Christina Chan

Publications and source records attributed to Christina Chan.

24 records · Page 2Linked to original sources

PubMed2003

Varicella vaccination in children with nephrotic syndrome: a report of the Southwest Pediatric Nephrology Study Group.

OBJECTIVE: To evaluate the safety and immunogenicity of varicella vaccine in children with nephrotic syndrome, including those taking low-dose, alternate-day prednisone. STUDY DESIGN: Prospective, open-label, multicenter clinical trial of varicella vaccine in a 2-dose regimen in US and Canadian children (12 months to <18 years) with nephrotic syndrome. Varicella Zoster Virus (VZV) antibody levels were measured after the first and second vaccine dose and yearly for 2 years. Patients were monitored for adverse reactions to vaccine, exposure to varicella, dermatomal zoster, and chickenpox. RESULTS: Twenty-nine children, mean age 4.9 (SD 1.9) years, 45% receiving every-other-day steroids, received 2 vaccine doses. All patients seroconverted and had VZV antibody levels considered protective against breakthrough varicella (>or=5 gpELISA units) after 2 doses. At 2-year follow-up, all patients retained detectable antibody, and 91% (21 of 23) had levels >or=5 gpELISA units. There were no adverse events associated with vaccination. CONCLUSIONS: Varicella vaccine was generally well tolerated and highly immunogenic in children with nephrotic syndrome, including those on low-dose, alternate-day prednisone.

Anti-Inflammatory Agents↗

PubMed2002

Use of statistical models for evaluating antibody response as a correlate of protection against varicella.

In vaccine clinical trials, humoral antibody responses are often used to measure the effect of a vaccine because they correlate with a vaccine's protective efficacy against the target disease. While the concept of a correlate of protection usually refers to establishing a protective level of antibody titre, identifying a clear-cut value is often impossible because vaccine efficacy is not related solely to the antibody titre. We propose examining the relationship between disease protection and the whole distribution of antibody responses rather than a single cut-off level. In particular, we use failure-time models to estimate the relationship between long-term disease breakthroughs and primary antibody responses after vaccination. We apply these models to show that the varicella antibody response measured by glycoprotein enzyme-linked immunosorbent assay 6 weeks after vaccination strongly correlate with protection against varicella (chickenpox); we used 7-year follow-up data from children who received one dose of a live attenuated varicella (Oka/Merck) vaccine. In addition, we explore the potential use of these models to predict long-term disease breakthrough rates and to estimate the predicted vaccine efficacy of a similar varicella vaccine made with a modified manufacturing process.

Antibodies, Viral↗

PubMed2002

Varicella vaccination in children with chronic renal failure. A report of the Southwest Pediatric Nephrology Study Group.

Children with kidney disease are at risk for serious varicella-related complications. To evaluate the safety and immunogenicity of a two-dose regimen of varicella vaccine in children (aged 1-19 years) with chronic renal insufficiency and on dialysis, the Southwest Pediatric Nephrology Study Group (SPNSG) undertook an open-label, multi-center, prospective 3-year clinical trial. Ninety-six patients without history of varicella were enrolled. Fifty (mean age 4.2 years) had no detectable varicella zoster virus (VZV) antibody; 98% seroconverted after the two-dose regimen. At 1, 2, and 3 years' follow-up, all patients studied maintained VZV antibody, including 16 who received a transplant. No significant vaccine-associated adverse events were seen. One subject developed mild varicella (10-50 maculopapular lesions) 16 months post transplant. In multivariate regression analysis, patients vaccinated after age 6 years had VZV antibody levels 73% (95% confidence interval 33%-89%) lower than patients vaccinated before age 6 years after controlling for gender, estimated glomerular filtration rate, and dialysis treatment. Adjusted analysis also showed that VZV antibody levels were lower after kidney transplantation, but this appeared to be a transient phenomenon. In this study, varicella vaccination with a two-dose regimen of varicella vaccine was generally well tolerated and highly immunogenic in children with chronic kidney disease.

Adolescent↗

PubMed2002

Metabolic pre-conditioning of cultured cells in physiological levels of insulin: generating resistance to the lipid-accumulating effects of plasma in hepatocytes.

Understanding the regulation of hepatocyte lipid metabolism is important for several biotechnological applications involving liver cells. During exposure of hepatocytes to plasma, as is the case in extracorporeal bioartificial liver assist devices, it has been reported that hepatic-specific functions, e.g., albumin and urea synthesis and diazepam removal, are dramatically compromised and hepatocytes progressively accumulate cytoplasmic lipid droplets. We hypothesized that the composition of hepatocyte culture medium significantly affects lipid metabolism during subsequent plasma exposure. Rat hepatocytes were cultured in medium containing either physiological (50 microU/mL) or supra-physiological (500 mU/mL) insulin levels for 1 week and then exposed to human plasma supplemented with or without amino acids. We found that insulin's anabolic effects, such as stimulation of triglyceride storage, were carried over from the pre-conditioning to the plasma exposure period. While hepatocytes cultured in high insulin medium accumulated large quantities of triglycerides during subsequent plasma exposure, culture in low insulin medium largely prevented lipid accumulation. Urea and albumin secretion, as well as the ammonia removal rate, were largely unaffected by insulin but increased with amino acid supplementation. Thus, hepatocyte metabolism during plasma exposure can be modulated by medium pre-conditioning and supplements added to plasma.

Albumins↗

PubMedDate not supplied

Application of multivariate analysis to optimize function of cultured hepatocytes.

Understanding the metabolic and regulatory pathways of hepatocytes is important for biotechnological applications involving liver cells, including the development of bioartificial liver (BAL) devices. To characterize intermediary metabolism in the hepatocytes, metabolic flux analysis (MFA) was applied to elucidate the changes in intracellular pathway fluxes of primary rat hepatocytes exposed to human plasma and to provide a comprehensive snapshot of the hepatic metabolic profile. In the current study, the combination of preconditioning and plasma supplementation produced distinct metabolic states. Combining the metabolic flux distribution obtained by MFA with methodologies such as Fisher discriminant analysis (FDA) and partial least squares or projection to latent structures (PLS) provided insights into the underlying structure and causal relationship within the data. With the aid of these analyses, patterns in the cellular response of the hepatocytes that contributed to the separation of the different hepatic states were identified. Of particular interest was the recognition of distal pathways that strongly correlated with a particular hepatic function. The hepatic functions investigated were intracellular triglyceride accumulation and urea production. This study illustrates a framework for optimizing hepatic function and a possibility of identifying potential targets for improving hepatic functions.

Algorithms↗

PubMedDate not supplied

Insulin concentration during preconditioning mediates the regulation of urea synthesis during exposure to amino acid-supplemented plasma.

Understanding the effects of preconditioning on cellular metabolism is important in providing insight into how cells and tissues may behave when confronted with alterations in their environment. Previously, elevated accumulation of lipids and a correspondingly reduced rate of urea synthesis were found in primary heptocytes preconditioned in culture medium containing high levels of insulin and then exposed to plasma. Subsequent studies found that preconditioning primary hepatocytes in medium containing low levels of insulin before exposure to plasma supplemented with amino acids was able to confer resistance to the lipid-accumulating effect of plasma exposure and restored urea synthesis. In the current study, we investigated the effects of insulin preconditioning and amino acid supplementation on the gene expression profile of the urea cycle and fatty acid metabolism enzymes. We found that insulin preconditioning mediates the effects of amino acids in the plasma exposure period on urea synthesis. Urea synthesis is regulated by insulin and amino acids through both short-term and long-term control. Possible mechanisms of long-term control through transcriptional regulation of urea synthesis by insulin, amino acids, and enzymes and transcription factors associated with lipid metabolism are discussed.

Adaptation, Physiological↗