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Biomedical subjects

Zoltan Laszik

Publications and source records attributed to Zoltan Laszik.

5 recordsLinked to original sources
PubMed2006

Chronic allograft nephropathy.

With the advent of calcineurin inhibitors, the success of kidney and other solid-organ transplants has improved significantly from the standpoint of reducing the incidence of acute rejection. Over the past 2 decades, both short-term allograft survival and acute rejection rates have dramatically improved with improved diagnostic and therapeutic techniques such as standardized pathology scoring; potent antirejection drugs such as anti-thymocyte globulin, interleukin-2 receptor antibodies, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil; and improved infection control such as valganciclovir and antifungal therapy. However, long-term graft loss has remained at nearly constant levels over the same period of time, with the average half-life of a deceased-donor kidney transplant in the United States remaining approximately 1 decade. In addition to death with a functioning allograft and calcineurin toxicity, a chronic fibrotic process-known at various times as chronic rejection, chronic allograft dysfunction, and chronic allograft nephropathy (CAN)-account for the leading causes of transplant failure.

Graft Survival↗
PubMed2005

Tamm-Horsfall protein acts as a general host-defense factor against bacterial cystitis.

AIMS: Tamm-Horsfall protein (THP) is urine's most abundant protein, but its biological function has remained elusive. Recently, THP-deficient (THP(-/-)) mice were shown to have difficulty clearing Escherichia coli from the urinary bladder. It has remained unclear if interaction between THP and E. coli is specific for E. coli or if THP has a versatile ability to clear a variety of bacteria from the bladder, and act as a broad host-defense mechanism against urinary tract infection (UTI). In this study, we examined the role of THP as a protective factor against UTI caused by bacteria other than E. coli, namely Klebsiella pneumoniae and Staphylococcus saprophyticus by determining if the THP(-/-) mouse has difficulty clearing these bacteria from its bladder. METHODS: THP gene knockout mice were generated by the technique of homologous recombination. K. pneumoniae and S. saprophyticus were introduced transurethrally, in separate experiments, into the bladders of the THP(-/-) and genetically similar wild-type (THP(+/+)) mice. Urine was collected at periodic intervals and cultured to quantitate the degree of bacteriuria. Bladders were surgically removed and examined histomorphometrically to determine the intensity of inflammation. RESULTS: Results showed that both with K. pneumoniae and with S. saprophyticus, the THP(-/-) mice had more severe bacteriuria in comparison with THP(+/+) mice. The inflammatory changes in the bladder were also markedly more intense in THP(-/-) mice with each of the bacterial species. CONCLUSIONS: These findings support the hypothesis that THP helps eliminate K. pneumoniae and S. saprophyticus from the urinary tract and acts as a general host-defense factor against UTI.

Adjuvants, Immunologic↗
PubMed2004

Tamm-Horsfall protein knockout mice are more prone to urinary tract infection: rapid communication.

BACKGROUND: Human colon contains many bacteria that commonly colonize the perineum and frequently enter the urinary tract. Uropathogenic Escherichia coli are the most common cause of urinary tract infection. Type 1 fimbriated E. coli have been associated with cystitis, and P fimbriated E. coli with pyelonephritis. Factors involved in clearing bacteria from the urinary tract are poorly understood. Tamm-Horsfall protein (THP), the most abundant protein in mammalian urine, has been postulated to play a role in defense against urinary tract infection but definitive proof for this idea has been lacking. METHODS: In this study, we generated THP gene knockout mice by the technique of homologous recombination, and examined if the THP-deficient (THP-/-) mice were more prone to urinary tract infection. Various strains of E. coli expressing type 1 or P fimbriae were introduced transurethrally into the bladders of the THP-/- and genetically similar wild-type (THP+/+) mice. Urine, bladder, and kidney tissues were obtained from the mice and cultured for bacterial growth. RESULTS: THP-/- mice inoculated with type 1 fimbriated E. coli had a longer duration of bacteriuria, and more intense colonization of the urinary bladder in comparison with THP+/+ mice. When inoculated with a P fimbriated strain of E. coli, the THP-/- mice showed no difference in kidney bacterial load when compared with the THP+/+ mice. CONCLUSION: These findings support the idea that THP serves as a soluble receptor for type 1 fimbriated E. coli and helps eliminate bacteria from the urinary tract.

Animals↗
PubMed2002

Nitric oxide synthase expression in hypertension induced by inhibition of glutathione synthase.

Induction of chronic oxidative stress by glutathione (GSH) depletion has been shown to cause hypertension in normal rats. This was accompanied by and perhaps in part due to inactivation and sequestration of NO by reactive oxygen species (ROS), leading to diminished NO bioavailability. This study was designed to examine renal histology, nitric oxide synthase (NOS) isotype expression, and nitrotyrosine distribution in this model. Sprague-Dawley rats were subjected to oxidative stress by administration of the GSH synthase inhibitor buthionine sulfoximine (BSO; 30 mM/l in drinking water) for 2 weeks. The controls were given tap water. Blood pressure, renal histology, tissue expression of endothelial and inducible NOS (eNOS and iNOS) and nitrotyrosine, tissue GSH content, and urinary excretion of NO metabolites (NOx) were examined. The BSO-treated group showed a 3-fold decrease in tissue GSH content, a marked elevation in blood pressure, and a significant reduction in the urinary excretion of NOx. Histological examination of kidneys revealed no significant abnormalities in either group. In addition, no significant differences were observed in either intensities or localizations of eNOS and iNOS in the kidney. However, the BSO-treated group exhibited intense accumulation in the renal tissue of nitrotyrosine, which is the footprint of NO oxidation by ROS. These observations suggest that oxidative stress-induced hypertension is not caused by either structural abnormality of or depressed NOS expression by the kidney in this model. Instead, it is associated with and perhaps partially related to enhanced renal NO inactivation by ROS and diminished NO bioavailability.

Animals↗