Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study determined the composition and nucleic-acid content of livers obtained from 11-wk-old, broiler-strain pullets infused with pituitary-derived chicken growth hormone (p-cGH) in either a pulsatile (Study 1) or continuous (Study 2) manner for 21 days. Pulsatile p-cGH administration resulted in a decrease in ratios for liver DNA to wet weight (P less than .01), DNA to protein (P less than .03), and DNA to RNA (P less than .002), compared with controls. Total RNA-to-liver ratio (P less than .003) and liver weight (P less than .007) were significantly elevated, compared with controls. Total grams of protein (P less than .0007), water (P less than .004), and ash (P less than .01) were also elevated, with no significant differences in the percentage of composition. Continuous growth-hormone (GH) administration resulted in a decrease in the DNA-to-protein ratio (P less than .04) and a modest increase in the mass of liver protein (P less than .11) in comparison with controls, suggestive of cell hypertrophy. On a mass and percentage basis, liver composition was otherwise unaffected by the continuous administration of GH. In summary, pulsatile administration of GH induced hepatomegaly, largely due to cell hypertrophy, with no change in relative tissue composition. The continuous administration of GH had no effect on liver size, tissue composition, or most nucleic-acid-based indicators of cell hypertrophy or hyperplasia. Thus, previously observed differences in overall growth performance due to pattern of GH administration were also reflected in selected target-tissue response.
 ...
PMID:Hepatomegaly induced by the pulsatile, but not continuous, intravenous administration of purified chicken growth hormone in broiler pullets: liver composition and nucleic-acid content. 169 89

Mouse models for urea cycle disorders have been available for the past 30 y; however, until now, no measurements of urea production in vivo have been conducted. Urea entry rate was determined in Otc(spf-ash) and littermate controls employing a primed-continuous infusion of 15N15N urea. A saline infusion control, a complete mixture of amino acids (AA), or a glycine-alanine (GA) mixture was infused at 86 (AA1 and GA1) and 172 mg N.kg(-1).h(-1) (AA2 and GA2) to impose a defined nitrogen load on the urea cycle. Urea entry rate and plasma urea concentration increased (P < 0.001) as a consequence of the increase in the infusion rate of the complete mixture of amino acids, but the 2 genotypes did not differ (P = 0.96 and P = 0.44, respectively). The infusion of the GA mixture, however, decreased (P < 0.001) the plasma urea concentration and urea entry rate in Otc(spf-ash) mice compared with controls. At the highest level (GA2), urea entry rate was further depressed (P < 0.001), Otc(spf-ash) mice became hyperammonemic (1701 +/- 150 micromol/L), and hyperammonemic symptoms were evident. An acute hepatic enlargement (P < 0.001) was also evident in Otc(spf-ash) mice infused with GA2. These results show that despite vestigial OTC activity, Otc(spf-ash) mice were able to maintain ureagenesis at the same rate of control animals when a complete mixture of amino acids was infused. This implies that Otc(spf-ash) mice are able to dispose of ammonia, without apparent adverse effects, when a balance mixture of amino acids is provided, despite reduced enzyme activity.
 ...
PMID:Reduced ornithine transcarbamylase activity does not impair ureagenesis in Otc(spf-ash) mice. 1654 67

We showed that Otc(spf-ash) mice, a model of ornithine transcarbamylase deficiency, were able to sustain ureagenesis at the same rate as control mice, despite reduced enzyme activity, when a complete mixture of amino acids was provided. An unbalanced amino acid mixture, however, resulted in reduced ureagenesis and hyperammonemia. To study the effect of ornithine supplementation [316 micromol/(kg.h)] on urea and glutamine kinetics in conscious Otc(spf-ash) mice under a glycine-alanine load [6.06 mmol/(kg.h)], a multiple tracer infusion protocol ([(13)C(18)O]urea, [5-(15)N]glutamine, [2,3,3,4,4 D(5)]glutamine and [ring-D(5)] phenylalanine) was conducted. Ornithine supplementation increased ureagenesis [3.18 +/- 0.88 vs. 4.56 +/- 0.51 mmol/(kg.h), P < 0.001], reduced plasma ammonia concentration (1125 +/- 621 vs. 193 +/- 94 micromol/L, P < 0.001), and prevented acute hepatic enlargement (P < 0.006) in Otc(spf-ash) mice. Ornithine supplementation also increased [96 +/- 20 vs. 120 +/- 16 micromol/(kg.h), P < 0.001] the transfer of (15)N from glutamine to urea, to values observed in the control mice [123 +/- 17 micromol/(kg.h)]. De novo amido-N glutamine flux was higher [1.57 +/- 0.37 vs. 3.04 +/- 0.86 mmol/(kg.h); P < 0.001] in Otc(spf-ash) mice, but ornithine supplementation had no effect (P < 0.56). The flux of glutamine carbon skeleton was affected by both genotype (P < 0.0001) and by ornithine (P 0. 036). In conclusion, ornithine supplementation restored ureagenesis, mitigated hyperammonemia, prevented liver enlargement, and normalized the transfer of (15)N from glutamine to urea. These data strongly suggest that ornithine has the potential for the biochemical correction of OTCD in Otc(spf-ash) mice.
 ...
PMID:Ornithine restores ureagenesis capacity and mitigates hyperammonemia in Otc(spf-ash) mice. 1677 45