Liver indications

As mentioned above, many transcription factors are not always active. Rather the activity of transcription factors is often achieved by induced reversible modification. Most frequently is the addition of phosphate groups (phosphorylation) to Ser, Thr, or Tyr residues. For the AP-1 component c-Jun the phosphorylation at Ser63 and Ser73 enhances activity when cells are subjected to stress, e.g. radiation. Phosphorylation is, however, dispensable for c-Jun-dqDendent tissue homeostasis in the liver, indicating that certain activities do not require the regulatory enhancement. Jun-N-teiminal kinase and a kinase called RSK or p38 catalyze the phosphorylation of AP-1. 

In adults, a study of 75 autopsies of persons who had resided in a soft-water, leached soil region of North Carolina found a positive correlation between lead level in the aorta and death from heart-related disease (Voors et al. 1982). The association persisted after adjustment for the effect of age. A similar correlation was found between cadmium levels in the liver and death from heart-related disease. (Aortic lead and liver cadmium levels were considered to be suitable indices of exposure.) The effects of the two metals appeared to be additive. Potential confounding variables other than age were not included in the analysis. The investigators stated that fatty liver (indicative of alcohol consumption) and cigarette smoking did not account for the correlations between lead, cadmium and heart-disease death. 

As a rule, the highest concentrations of a poison are found at the site of administration. A large quantity of drug in the GI tract and liver indicates oral ingestion. The gastrointestinal (GI) tract may contain large amounts of unabsorbed toxicant. Cases that involve the oral administration of toxicants indicate analysis of GI contents. However, the presence of toxic material in the GI tract does not provide sufficient evidence that the agent is the cause of death. Absorption and transport of the toxicant to the site of action must be demonstrated. Blood and tissue analysis is necessary and would still be paramount. 

Shulman, G.E. and Nigmatullin, C.M. (1981). Changes in liver indices of the squid Stenoteuthis oualaniensis from the tropical Indian Ocean under experimental conditions (In Russian). Ekologiya Morya 5,95-103. 

Digestion studies using homogenates of kidneys, intestine, and liver indicated a close relationship between the levels of aminopeptidase activity as measured with a specific synthetic substrate and that based on the enzymatic activity responsible for hydrolyzing the isopeptide bond (see Table V). Purified aminopeptidase N from the intestinal brush border of rabbit (68) and pig (64) hydrolyzed a dipeptide and the related isodipeptide with about the same efficiency (see Table VI). These results may explain the findings that methionine covalently bound... 

A (D-glucosylamine)uronic acid derivative has been identified331 as the metabolite of carbamazepine (5//-dibenz[fe,/]azepine-5-carbox-amide, an anti-epileptic agent) by means of permethylation, g.l.c., and mass spectometry. Analytical data for the conjugate (identified in the bile of the isolated, perfused, rat liver) indicated that the carboxamide nitrogen atom is linked to C-l of the sugar moiety. 

Additional studies with fetal guinea pig livers indicated a marked variation in cytochrome P450 and O-demethylase activity in individual fetal livers these findings correlated well with the concentration of liver... 

With selenium or Vitamin E deficient diets, repeated exposure to silver (76 ppm in the drinking water for 52 days) in rats elicited hepatic necrosis and ultra-structural changes in the liver indicative of oxidative damage. This toxicity may be related to a silver-induced selenium deficiency and impairment of synthesis of the enzyme glutathione peroxidase. Dietary supplementation with selenium or Vitamin E prevented such changes. Mice exposed to silver nitrate in the drinking water for 4 months exhibited... 

In subchronic studies rats inhaling 8800mgm (2000 ppm) vinyl bromide 8 h per day for 5 days a week for 8-15 weeks developed ATP-ase deficient foci in the liver, indicative of its carcinogenic potential, which is also in agreement with its mutagenicity in almost every test system. 

A literature review of animal experimental studies with tryptophan and carcinogenesis, particularly involving bladder and liver, indicates that tryptophan alone does not induce tumors but is capable of acting in many cases as a promoting agent in chemical carcinogenesis. Whether this effect is due to tryptophan alone or to tryptophan metabolites is not clear. In the induction of bladder cancer, tryptophan metabolites are clearly implicated. 

Early work in fractionated extracts of both Escherichia coli and liver indicated the participation of a vitamin Bi2-containing protein in the reaction of homocysteine with 5-methyltetrahydrofolate to form methionine and tetrahydrofolate. ° The reaction was stimulated by SAM, although SAM was not the stoichiometric methyl donor. Methylcobalamin was not the primary methyl donor however, it could serve as a methyl donor in the absence of 5-methyltrahydrofolate. It was suggested that methylcobalamin could be a catalytic intermediate in methyl transfer from 5-methyltetrahydrofolate. The role of SAM remained obscure until recent years, when it was found to preserve enzyme activity by maintaining cobalamin as methylcobalamin in the Bi2-protein. 

Most studies with isolated hepatocytes or perfused liver indicate the existence of a ApH across the mitochondrial membrane, ranging from 0-0.6 [33,34,37-39], but under some conditions the calculated ApH depends on the metabolite chosen. This indicates disequilibrium in one or more of the transport steps. Under most conditions it is unlikely that the phosphate translocator is out of equilibrium because of its very high (Table 1). Problems do arise, however, when the dicarboxylate translocator is out of equilibrium because it connects the movement of citrate, malate and a-oxoglutarate with that of H. In that case the above equation cannot... 

Studies with radioactive glycocholate or taurocholate demonstrated a virtual absence of the enterohepatic circulation of bile acids in patients with jejunotransversocolostomy (77). The small amount of absorbed bile acids contained some deconjugated cholate and deoxycholate (which had been reconjugated in the liver), indicating a rapid bacterial action during an apparently fast intestinal passage. Under these conditions, steatorrhea is apparently not solely due to bile salt deficiency induced impairment of micelle formation, but reduced absorptive area may play an important contributory role. No direct measurement of bile acid synthesis by fecal determination has been performed in this condition. 

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