Biomedical subjects

C Theodoropoulos

Publications and source records attributed to C Theodoropoulos.

5 recordsLinked to original sources

PubMed2001

Expression of CYP27A, a gene encoding a vitamin D-25 hydroxylase in human liver and kidney.

Vitamin D3 (D3) is not active but must be hydroxylated at C-25 in liver before acquiring its hormonal potential in the kidney. The sterol-27 hydroxylase (gene symbol: CYP27A) catalyses the oxidation of sterol side chain in bile acid synthesis but the enzyme is also known as a D3-25 hydroxylase. The study examined the expression of the gene encoding CYP27A in adult and fetal human livers and kidneys. Thirty-nine adults (18 men and 21 women; mean age 58 years in men and 57 years in women) and three normal fetuses gestational age 17-19 weeks were studied. Tissue CYP27A mRNA and serum 25OHD concentrations were measured. Normal specimens: CYP27A transcript was found to be higher in adult than in fetal livers but its expression was similar in adult and fetal kidneys. In fetuses, no difference was observed between CYP27A levels in livers and kidneys. In adult livers CYP27A levels were higher in women than in men. Hepatic CYP27A mRNA and serum 25OHD concentrations were both found to be higher in summer than in winter. Multiple linear regression analyses indicate that the season of the year and the serum 25OHD concentrations (but not 1,25(OH)2D concentrations) are the best predictors of CYP27A mRNA abundance in normal adult livers. In situ hybridization illustrates a clear label in hepatocytes which increases in intensity in the perivenous region of the hepatic acinus. Pathological specimens: In one man with an hepatic carcinoma there was a very large increase in CYP27A (> 1000 fold) compared to the level found in the normal liver. In that patient, serum 25OHD concentrations were found to be high considering the level of CYP27A mRNA in the normal hepatic area suggesting that the neoplastic tissue contributed to the C-25 hydroxylation of vitamin D. Specimens obtained from two patients suffering from focal hepatic hyperplasia indicate that in one case the level of CYP27A mRNA was twice as high in the pathological than in the normal area while in the other its levels were similar in both areas. No difference in the CYP27A transcript was observed between specimens obtained from normal areas and those obtained form either an hepatic adenoma or from two intrahepatic colonic metastases. CYP27A is present not only in the human adult liver but also in the adult kidney, and in the fetal liver and kidney. Our findings illustrate that CYP27A can be significantly upregulated in certain pathological situations such as in hepatic carcinoma and that the neoplastic tissue could contribute to the circulating concentration of 25OHD.

Adenoma↗

PubMed2001

Plesiomonas shigelloides enters polarized human intestinal Caco-2 cells in an in vitro model system.

This study provides the first definitive evidence that the gram-negative bacterium Plesiomonas shigelloides adheres to and enters eukaryotic intestinal host cells in vitro. P. shigelloides is increasingly regarded as an emerging enteric pathogen and has been implicated in intestinal and extraintestinal infections in humans. However, the establishment of its true role in enteric disease has been hindered by inadequacies in experimental design, deficiencies in clinical diagnosis, and the lack of an appropriate animal model. In this investigation, an in vitro system was used to evaluate plesiomonad pathogenesis. Differentiated epithelium-derived Caco-2 cell monolayers inoculated apically with 12 isolates of P. shigelloides from clinical (intestinal) origins were examined at high resolution using transmission electron microscopy. Bacterial cells were observed adhering to intact microvilli and to the plasma membrane on both the apical and the basal surfaces of the monolayer. The bacteria entered the Caco-2 cells and were observed enclosed in single and multiple membrane-bound vacuoles within the host cell cytoplasm. This observation suggests that initial uptake may occur through a phagocytic-like process, as has been documented for many other enteropathogens. P. shigelloides also was noted free in the cytosol of Caco-2 cells, suggesting escape from cytoplasmic vacuoles. Differences in invasion phenotypes were revealed, suggesting the possibility that, like Escherichia coli, P. shigelloides comprises different pathogenic phenotypes.

Bacterial Adhesion↗

PubMed2001

1,25-Dihydroxyvitamin D(3) downregulates the rat intestinal vitamin D(3)-25-hydroxylase CYP27A.

The vitamin D(3)-25-hydroxylase CYP27A is located predominantly in liver, but its expression is also detected in extrahepatic tissues. Our aim was to evaluate the regulation of CYP27A by vitamin D(3) (D(3)) or its metabolites in rat duodena. Vitamin D-depleted rats were repleted with D(3), 25-hydroxyvitamin D (25OHD), or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] or acutely injected 1,25(OH)(2)D(3) to investigate the mechanisms of action of the hormone. All D(3) compounds led to a progressive decrease in CYP27A mRNA, with levels after D(3) representing 20% of that observed in D depletion. 25OHD decreased CYP27A mRNA by 55%, whereas 1,25(OH)(2)D(3) led to a 40% decrease, which was accompanied by a 31% decrease in CYP27A protein levels and an 89% decrease in enzyme activity. Peak circulating 1,25(OH)(2)D(3) concentrations were, however, the highest in D(3)-repleted, followed by 25OHD- and 1,25(OH)(2)D(3)-repleted animals. 1,25(OH)(2)D(3) resulted in a decrease in both CYP27A mRNA half-life and transcription rate. Our data illustrate that the intestine expresses the D(3)-25-hydroxylase and that the gene is highly regulated in vivo through a direct action of 1,25(OH)(2)D(3) or through the local production of D(3) metabolites.

Animals↗

PubMed2000

"Coarse" stability and bifurcation analysis using time-steppers: a reaction-diffusion example.

Evolutionary, pattern forming partial differential equations (PDEs) are often derived as limiting descriptions of microscopic, kinetic theory-based models of molecular processes (e.g., reaction and diffusion). The PDE dynamic behavior can be probed through direct simulation (time integration) or, more systematically, through stability/bifurcation calculations; time-stepper-based approaches, like the Recursive Projection Method [Shroff, G. M. & Keller, H. B. (1993) SIAM J. Numer. Anal. 30, 1099-1120] provide an attractive framework for the latter. We demonstrate an adaptation of this approach that allows for a direct, effective ("coarse") bifurcation analysis of microscopic, kinetic-based models; this is illustrated through a comparative study of the FitzHugh-Nagumo PDE and of a corresponding Lattice-Boltzmann model.

Computer Simulation↗

PubMed1985

Alpha 1-antitrypsin and cancer of the pancreas.

Serum levels of alpha-1-antitrypsin (alpha 1-AT) were measured and phenotypes were determined in 47 patients with cancer of the pancreas and in 160 hospital controls. The mean value of alpha 1-AT (+/- SEM) in cases with cancer of the pancreas was 486 (+/- 18) mg/100 ml, and it was significantly higher than the corresponding mean value in controls, which was 434 (+/- 13) mg/100 ml (p approximately 0.02). The frequency distribution of the cases of pancreatic cancer by alpha 1-AT phenotype was: M1M1 49%, M1M3 21% and other phenotypes 30%, whereas the corresponding frequency distribution among controls was: M1M1 53%, M1M3 21% and other phenotypes 26%; the two distributions are clearly compatible (p greater than 0.50).

Female↗