Biomedical subjects

A S Tavill

Publications and source records attributed to A S Tavill.

5 recordsLinked to original sources

PubMed1978

The control of hepatic iron uptake: correlation with transferring synthesis.

The control of hepatic iron uptake was studied in the perfused liver isolated from rats subjected to nutritional iron deficiency. The total hepatic iron uptake and incorporation into ferritin was found to be higher in iron deficiency and during the 48 h of oral refeeding with iron than in the normal state. Specific incorporation of iron into feritin from a perfusate of normal transferrin iron saturation was enhanced in nutritional iron deficiency as compared to controls after 5 h of perfusion but not after 1 h, suggesting that increased uptake of iron from the perfusate may play a role in stimulating hepatic ferritin synthesis and assembly. This promotion of uptake into ferritin was inhibited by cycloheximide suggesting that enhanced incorporation of iron is dependent upon de novo synthesis of apoferritin. In control, nutritionally iron deficient and iron-refed rats there was a significant, direct correlation between the transferrin-iron saturation of the perfusate at physiological transferrin concentrations and total hepatic iron uptake after 5 h perfusion. A significant positive correlation was found between the hepatic total and ferritin iron uptake and the transferrin synthetic rate measured in the same liver. It is proposed that in the liver the negative feedback of iron supply on transferrin synthesis may be linked with a positive feedback on ferritin synthesis. The time-course of these reciprocal responses suggests a role for hepatic ferritin and/or a component of the non-haem, non-ferritin iron pool in the regulation of transferrin synthesis.

Animals↗

PubMed1977

The role of iron in the regulation of hepatic transferrin synthesis.

The role of iron supply in the regulation of hepatic transferrin synthesis by the isolated perfused rat liver was studied using nutritional iron deficiency as the experimental model. The increased transferrin release encountered in iron deficiency could be equated with enhanced de novo synthesis as evidenced by the inhibitory effects of cycloheximide and measurements of intrahepatic protein pools before and after perfusion. Refeeding with iron, sufficient to restore plasma iron and hepatic ferritin iron but before correction of anaemia, promoted a reduction towards normal in the transferrin synthetic rate. This effect was not produced by transfusional correction of the anaemia, suggesting a specific response to iron supply. Phenobarbitone treatment, which produced a marked fall in hepatic ferritin iron concentration but no change in haemoglobin or plasma iron concentrations, promoted a specific enhancement of transferrin synthesis in both control and iron deficient livers. The concentration of liver iron stores appears to be a major regulatory factor in the control of hepatic transferrin synthesis.

Animals↗

PubMed1976

Studies of tryptophan and albumin metabolism in a patient with carcinoid syndrome, pellagra, and hypoproteinemia.

Detailed studies of protein metabolism were undertaken in a patient with pellagra and hypoproteinemia associated with the carcinoid syndrome both before and after treatment. The synthesis of albumin improved from 82 mg per kg per day to 135 mg per kg per day with little change in the daily excretion of 5-hydroxyindole acetic acid. After treatment with nicotinamide the patient made good progress with a complete resolution of the signs of pellagra and protein malnutrition. These results support the hypothesis that a reduced availability of the essential amino acid L-tryptophan may limit the synthesis of albumin and nicotinic acid in patients with the carcinoid syndrome who become anoretic.

Adult↗

PubMed1975

Hepatic albumin and urea synthesis: The mathematical modelling of the dynamics of [14C]carbonate-derived guanidine-labelled arginine in the isolated perfused rat liver.

A mathematical model was constructed to define the dynamics of incorporation of radioactivity into urea carbon and the guanidine carbon of arginine in plasma albumin after the rapid intraportal-venous administration of Na214CO3 in the isolated perfused rat liver. 2. The model was formulated in terms of compartmental analysis and additional experiments were designed to provide further information on subsystem dynamics and to discriminate between alternative model structures. 3. Evidence for the rapid-time-constant of labelling of intracellular arginine was provided by precursor-product analysis of precursor [14C]carboante and product [14C]urea in the perfusate. 4. Compartmental analysis of the dynamics of newly synthesized urea was based on the fate of exogenous [13C]urea, endogenous [14C]urea and the accumulation of [12C]urea in perfusate water, confirming the early completion of urea carbon labelling, the absence of continuing synthesis of labelled urea, and the presence of a small intrahepatic urea-delay pool. 5. Analysis of the perfusate dynamics of endogenously synthesized and exogenously administered [6-14C]arginine indicated that although the capacity for extrahepatic formation of [14C]-urea exists, little or no arginine formed within the intrahepatic urea cycle was transported out of the liver. However, the presence of a rapidly turning-over intrahepatic arginine pool was confirmed. 6. On the basis of these subsystem analyses it was possible to offer feasible estimations for the parameters of the mathematical model. However, it was not possible to stimulate the form and magnitude of the dynamics of newly synthesized labelled urea and albumin which were simultaneously observed after administration of [14C]carbonate on the basis of a preliminary model which postulated that both products were derived from a single hepatic pool of [16-14C]arginine. On the other hand these observed dynamics could be satisfied to a two-compartment arginine model, which also provided an explanation for discrepancies observed between albumin synthesis measured radioisotopically and immunologically. This was based on a relative overestimation of [14C]urea specific radioactivity resulting from the rapid dynamics of [14C]carbonate and the [14C]urea subsystem relative to the labelled albumin subsystem. The effects of arginine compartmentalization could be minimized in the model by minor slowing of the rate of [14C]carbonate turnover or by constant infusion of [14C]carbonate, both of which permitted valid determination of albumin-synthesis rates.

Animals↗

PubMed1975

A proposed role for alpha1 macroglobulin in the promotion of alpha1 acute-phase globulin synthesis by the perfused rat liver.

The effects of intravenously administered rat alpha1 macroglobulin (alpha1M), alone and in combination with pancreatic trypsin, on the synthesis of alpha1 acute-phase globulin (alpha1AP globulin) have been measured in the isolated perfused rat liver 24 h after injection. Maximum promotion (approximately five-fold) of alph1AP globulin synthesis was observed after administration of alpha1M complexed with trypsin or alpha1M alone, which after purification had lost most of its trypsin-protein-esterase (T.P.E.) activity. Slightly lesser but still significant degrees of enhancement (approximately four-fold) of alpha1AP globulin synthesis resulted from the injection of alpha1M alone or complexed with trypsin, which after purification had retained sitnificant T.P.E. activity. All these responses were greater than those generated by injection of trypsin or plasma alone, or rabbit plasma complexed with trypsin. However, the synthetic response did not reach the maximum rate observed 24 h after an intramuscular injection or sterile turpentine. An hypothesis is proposed for the role of alpha1 macroglobulin (and its homologue in man, alpha2 macroglobulin) in the mediation of the acute-phase synthetic response by the liver. This predominantly intravascular glycoprotein serves as the principal circulatory porteinase binder. Proteinases released in response to tissue injury, necrosis or inflammation would be bound and inactivated by alpha1M, and in turn the alpha1M-proteinase complex would stimulate the liver to synthesize a number of acute-phase proteins. Certain of these, e.g. alpha2 acute-phase globulin also possess proteinase binding activity and, being of low molecular weight, would be more effective than alpha1M in the inactivation of released tissue enzymes at extravascualr sites. The data presented in this paper are compatible with this biphasic role for plasma proteinase inhibitors in the biological response to injury.

Albumins↗