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Biomedical subjects

A Panduro

Publications and source records attributed to A Panduro.

32 records · Page 2Linked to original sources

Differential regulation in the expression of hepatic genes in nephrotic and pair-fed rats.

The messenger ribonucleic acid (mRNA) levels of albumin, fibrinogen, alpha 1-acid glycoprotein (pAGP) and transferrin were analyzed in puromycin aminonucleoside (PAN)-treated (nephrotic) and in pair-fed (PF) rats with the Northern and dot blot hybridization techniques. Albumin mRNA levels in nephrotic and PF rats were 2- and 1.5-fold higher, respectively, than in ad-libitum-fed control (C) rats 6 days after PAN treatment. On day 11, this mRNA in PAN-treated rats was 2.5-fold higher than in PF and 4-fold higher than in C rats. A differential expression at the level of specific mRNAs was also detected for fibrinogen, pAGP, and transferrin in nephrotic and PF rats. On day 6, the fibrinogen and transferrin mRNA levels were significantly higher (p < 0.05) in nephrotic than in PF rats. In contrast, pAGP mRNA levels were normal or low in nephrotic rats and increased 2-fold in PF rats. These studies indicate the differential expression of hepatic genes in nephrotic and PF rats and show that albumin gene expression is only partially regulated by diet during the nephrotic stage of the disease.

Albumins↗

Angiotensin I-converting enzyme activity in rats with carbon tetrachloride-induced acute renal failure.

The angiotensin I-converting enzyme (ACE) activity was measured in urine, serum, and tissues from rats with carbon tetrachloride (CCl4)-induced acute renal failure on days 1, 2, 3, and 7 after CCl4 administration. Serum ACE increased on days 1 to 3. Heart, lung, small intestine, brain, and testis ACE decreased, whereas kidney and liver ACE remained unchanged. Urine ACE activity increased from day 1 to day 3. Our data suggest that the increase in serum ACE may be secondary to the ACE release from the damaged tissues, and that the urine ACE increase may be due to the kidney proximal tubule damage. This work supports the contention that an increase in urine ACE may be an indicator of damage to the proximal tubule.

Acute Kidney Injury↗

Albumin gene expression is down-regulated by albumin or macromolecule infusion in the rat.

A novel feedback regulatory mechanism operating on transcription of the albumin gene is described in the rat. In 1946, it was proposed that circulating colloids, including serum albumin, may affect the synthesis and/or secretion of albumin in the liver. The molecular basis for this proposed regulation has now been investigated by adding oncotically active macromolecules to the circulation of normal or genetically albumin-deficient Nagase analbuminemic rats (NAR) and analyzing the hepatic expression of genes, including albumin after 24 h. The transcription rate of the albumin gene was higher in NAR than in normal rats and was dramatically reduced by raising serum albumin to 1.6 g/dl. Intravenous infusion of albumin into normal rats also decreased transcriptional activity of the albumin gene by 50-60%, and this decrease correlated with changes in serum colloid osmotic pressure after albumin infusion. Inhibition of albumin gene transcription was also observed upon intravenous infusion of other protein or nonprotein macromolecules, such as gamma-globulin and dextran. This down-regulation appears to control the steady-state level of albumin mRNA in the liver. Aside from a concomitant decrease in apo E gene transcription after albumin or macromolecule infusion, there was no change in the transcription rate of other genes, including those exhibiting liver-preferred or -specific expression (e.g., tyrosine amino-transferase, cytochrome P-450, alpha 1-antitrypsin, apolipoproteins A-I and B, and transferrin) or general cellular expression (e.g., alpha-tubulin, pro alpha 2 collagen, and beta-actin). Feedback regulation of albumin gene expression by serum colloids may serve as a specific homeostatic mechanism to maintain the steady-state level of total protein in the circulation.

Animals↗

Changing patterns of transcriptional and post-transcriptional control of liver-specific gene expression during rat development.

Genes coding for unique or tissue-specific (differentiated) functions in the liver are induced at different times during development. It has generally been felt that transcriptional control represents the dominant mechanism for regulating expression of these genes. We have determined the relative transcription rates and mRNA steady-state levels for a series of genes specifically or preferentially expressed in rat liver and find examples of transcriptional control (albumin, alpha-fetoprotein, alpha 1-antitrypsin, tyrosine aminotransferase, transferrin, and cytochrome P450, TF-1) and post-transcriptional control (alpha 1-acid glycoprotein, apolipoproteins A-1 and E, malic enzyme, and ATP citrate lyase), as well as "mixed" regulation (ligandin and cytochrome P450, R17). Examples have been identified in which the predominant mode for regulating expression of preferentially expressed genes changes from transcriptional to post-transcriptional at different stages of liver development and some members of multigene families (cytochrome P450s and apolipoprotein genes) also show independent and sometimes contrasting modes of regulation. Therefore, it appears that regulation of specific gene expression in the liver is a dynamic process, far more complex than heretofore suspected, and a much greater contribution of post-transcriptional regulation accounts for changes in expression of genes representing major functions of the liver.

ATP Citrate (pro-S)-Lyase↗

Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration.

During liver regeneration induced by CCl4 administration to rats, changes in the relative transcription rates of albumin and alpha-fetoprotein genes have been measured in conjunction with other liver-specific and general cellular function genes. Within 24 h following CCl4 administration, albumin gene transcription decreases by 85%, whereas alpha-fetoprotein transcription increases from undetectable levels to 50% of that observed for albumin. These changes precede maximal [3H]thymidine incorporation into DNA which peaks at 48 h. Other genes related to liver-specific functions, such as ligandin, alpha 1-antitrypsin, and cytochrome P-450's, as well as general cellular genes pro alpha 1- and pro alpha 2-collagen, beta-actin, and alpha-tubulin, respond in kinetic patterns often distinct from each other and from albumin and alpha-fetoprotein. Changes in the steady-state levels of albumin and alpha-fetoprotein mRNA correlate with changes in transcription, but there is a lag in alpha-fetoprotein mRNA accumulation, which peaks at 72 h following CCl4 administration. These studies indicate that reciprocal changes in albumin and alpha-fetoprotein gene transcription occur during CCl4-induced liver regeneration, leading to changes in the level of these specific mRNAs. These changes precede DNA synthesis and would appear to represent an alteration in differentiated function of hepatocytes in conjunction with the liver regenerative process.

Actins↗

Changes in albumin, alpha-fetoprotein and collagen gene transcription in CCl4-induced hepatic fibrosis.

In efforts to understand mechanisms of liver dysfunction in cirrhosis, transcription of specific genes important to liver function has been measured in the rat model of CCl4-induced hepatic fibrosis. The relative transcription rates of albumin, alpha-fetoprotein and pro-alpha 1-collagen genes were studied during development of fibrosis and after fibrosis was established. During the initial phase of CCl4 administration, there was a decrease in albumin transcription associated with increased alpha-fetoprotein transcription, indicative of active liver regeneration. However, later during development of fibrosis, the response pattern of these genes was different, as albumin gene transcription was normal or increased and alpha-fetoprotein gene transcription was no longer increased. Three weeks after completion of CCl4 treatment (fully established cirrhosis), albumin genes responded normally or hypernormally to an acute regenerative stimulus, but the alpha-fetoprotein gene was again not measurably responsive. Pro-alpha 1-collagen gene transcription increased during the entire fibrogenic process and remained elevated after cirrhosis was established. These studies suggest that a switch from albumin to alpha-fetoprotein gene transcription can serve as a marker of liver regenerative capacity, and that this process is altered during and after development of hepatic fibrosis. The fibrogenic process is also associated with elevated transcription of collagen genes.

Animals↗

[The PCR in gastroenterology].

The polymerase chain reaction (PCR) is a molecular biology technique that can significantly amplify DNA or RNA. With the use of recombinant DNA technology, PCR has allowed a spectrum of advances in diagnostic pathology, specially in the fields of viral diseases, hematology and genetic diseases. This work describes the basic aspects, as well as specific issues of the PCR technique. It also contains protocols and experimental conditions that are being used in our laboratory in the diagnosis of hepatitis B (HBV), hepatitis C (HCV) and in the amplification of specific sequences of the APC gene.

Base Sequence↗

[New strategies in the clinical evaluation of patients with colon cancer based on molecular studies].

During the last five years molecular studies allowed important advances in the knowledge of cancer colon with important clinical implications. The main finding was the identification and sequence analysis of the APC gen. Structural alterations of this gene have been detected in patients with Familial Adenomatous Polyposis and Gardner syndrome, which suggest a common disease. Furthermore, alterations of the APC gen appears to be also altered in cases of cancer of colon sporadic. Indicating that structural alteration of the APC gen can be inherited and/or acquired. Restriction fragment-length polymorphisms in the chromosome 5q21-22 can now be used clinically for premorbid diagnosis and counseling in familial adenomatous polyposis. The molecular studies allow the clinician to have a new approach in the management and screening of families with familial adenomatous polyposis. The sequence analysis and specific identification of the structural alteration of the APC gene is a more expensive and sophisticated study, although represent a more direct approach. In the Department of Gastroenterology of the INNSZ we are performing such molecular studies. The main purpose of our group is to proportionate integral clinical-molecular studies for families with hereditary colon cancer, create a national register of these diseases and investigate the molecular bases in order to generate new molecular diagnosis tools.

Adenomatous Polyposis Coli↗

Hepatic phenylalanine-hydroxylase and tyrosine-aminotransferase mRNA levels in rats adapted to diets with different concentrations of protein.

The effect of dietary protein concentrations on the hepatic expression of phenylalanine hydroxylase (PAH) and tyrosine aminotransferase (TAT) mRNA concentrations was studied in rats adapted to consume diets (18 or 50% casein) in a restricted schedule of 7 h (0900 to 1600) for 5 days. After 6 hours of feeding, TAT mRNA concentrations of rats adapted to 18% casein diet and fed acutely 6, 18 and 50% casein diet were 0.15, 0.84 and 5.08 fold respectively higher than mRNA concentrations of rats before feeding. After 17 hours of fasting, TAT mRNA concentrations of rats previously fed 6, 18 or 50% casein diet were -0.45, 1.76 and 9.11 fold respectively higher than mRNA concentrations of rats before they were fed. PAH mRNA concentrations showed a similar pattern. There was a -0.68, 1.63 and 2.5 fold rise of PAH mRNA concentrations in rats fed 6,18 and 50% casein diet during the feeding period, and -0.86, 2.32 and 9.33 fold rise after 17 hours of fasting. TAT and PAH mRNA concentrations of rats adapted to consume 50% casein diet and then changed to 6% or kept on the 50% casein diet showed a maximum peak 6 hours after the rats began to consume the diet; however, they decreased 5 hours after fasting. These results suggest that increasing concentrations of protein in the diet were able to increase the concentration of TAT and PAH mRNA, possibly in order to eliminate the excess of amino acids consumed. The concentration of TAT and PAH mRNA depended more on the protein content of the diet to which the rats were previously adapted.

Animals↗