Sham-operated Livers Research Articles

Hepatic adenine nucleotides and microsomal cholesterol 7 alpha-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction.

The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure. The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7 alpha-hydroxylase activities and by hepatic adenine nucleotide and energy charge levels. The values were compared with those in sham-operated control liver. Cholesterol 7 alpha-hydroxylase activities were determined by gas-liquid chromatography-mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography. The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissue linking portal areas. Microsomal cholesterol 7 alpha-hydroxylase activities, hepatic energy charge and adenine nucleotide levels did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver. Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in either BDO or FD lobes of the liver.

Hepatic adenine nucleotides and microsomal cholesterol 7 alpha-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction.

The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure. The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7 alpha-hydroxylase activities and by hepatic adenine nucleotides and energy charge levels. The values were compared with those in the sham-operated control liver. Cholesterol 7 alpha-hydroxylase activities were determined by gas-liquid chromatography--mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography. The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissues linking portal areas. Microsomal cholesterol 7 alpha-hydroxylase activities, hepatic energy charge and each adenine nucleotide level did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver. Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in both the BDO and FD lobes of the liver.

Assessment of damage and recovery of sinusoidal endothelial cell function by in vivo hyaluronic acid uptake in cold-preserved and transplanted rat livers.

We sought to evaluate the significance of endogenous hyaluronic acid levels and in vivo uptake of exogenous hyaluronic acid as markers of liver endothelial cell damage and correlate these findings to graft survival/function in a rat orthotopic liver transplant model. Endogenous hyaluronic acid levels were measured after orthotopic liver transplantation performed with freshly explanted livers, with livers preserved for 30 hr, and after sham operation. Exogenous hyaluronic acid uptake was evaluated in six study groups: fresh liver grafts, livers preserved for 12 hr, 24 hr, 30 hr and 48 hr, and sham-operated livers. Endogenous hyaluronic acid levels fell after orthotopic liver transplantation with freshly harvested livers and after sham operation, but rose in animals transplanted with livers preserved for 30 hr (P<0.01 vs. sham operation). In the preserved group, there was no difference in endogenous hyaluronic acid levels between survivors and nonsurvivors. Uptake of exogenous hyaluronic acid was significantly lower after orthotopic liver transplant with grafts preserved for 12 hr than after sham operation or orthotopic liver transplant with nonpreserved livers (P<0.05). Hyaluronic acid uptake further deteriorated in the 24-, 30-, and 48-hr groups. No significant difference in hyaluronic acid elimination rate was found when results obtained from livers preserved for extended periods (>12 hr) were compared in survivors and nonsurvivors. Hyaluronic acid uptake was reevaluated in surviving animals after 2 weeks. Completely restored function was observed in all survivors, indicating recovery of endothelial cells. We conclude that endogenous hyaluronic acid levels and exogenous hyaluronic acid uptake are reliable markers of liver sinusoidal endothelial cell function and that normal or moderately compromised hyaluronic acid uptake is associated with good graft function. On the other hand, endothelial cell dysfunction suggested by poor hyaluronic acid elimination is not a completely reliable predictor of subsequent deterioration of graft function in rat liver transplantation.

Hepatic adenine nucleotides and DNA synthesis during the regenerative and atrophic process of the liver lobes after selective portal vein ligation.

Selective portal vein occlusion prior to aggressive hepatic resection is now an alternative way to decrease postoperative morbidity and mortality rates. However, the detailed changes in the hepatic energy status and DNA synthesis rate in both portal vein ligated (PVL) and nonligated (PVNL) lobes of the liver are not clear. In rats, the portal branch that supplies 70% of the liver volume was ligated, and changes in arterial ketone body ratio (AKBR), liver weight, histology, DNA synthesis rate and adenine nucleotides of the PVL and PVNL liver lobes were determined before and 1, 2, 4 and 7 days after portal vein ligation, and compared with those in sham-operated rats. The weight of the PVL lobes decreased, while that of the PVNL lobes increased depending on time. The DNA synthesis rates of the PVNL lobes were significantly higher than those in sham-operated control liver during the first 4 days with the maximal value on the 2nd day, while those of PVL lobes were essentially similar to the control values. Energy charge (EC) in both PVL and PVNL lobes significantly decreased on day 1 and recovered gradually, but with less extent in the regenerating PVNL lobes. The concentrations of total adenine nucleotides (TAN) in both the PVL and PVNL lobes were essentially similar during the first 2 days, but became significantly lower in PVL lobes after day 4. A decrease in EC preceded an increase in DNA synthesis only in the PVNL lobes, in contrast to the PVL lobes. Mitosis of hepatocytes on day 2 and subsequently enlarged lobules with an increased number of hepatocytes were histologic features in the PVNL liver. The AKBR was not correlated with hepatic energy charge of the liver. In conclusion, PVNL liver regenerates preceded by a decrease in EC and a subsequent increase in DNA synthesis keeping TAN constant, while PVL liver becomes atrophic, with a similar change in EC of the PVNL liver but ultimately decreased TAN without any change in DNA synthesis. AKBR is not a parameter reflecting the hepatic EC after portal branch ligation.

Increased serum levels of dipeptidyl peptidase IV (CD26) in rats undergoing liver regeneration

Dipeptidyl Peptidase IV (DPP IV; CD26) is a cell surface ectopeptidase that has been shown to alter the binding of hepatocytes to the extracellular matrix (ECM), play a role in lymphocyte proliferation and alter the biological activity of several proteins. During hepatic regeneration, there is obvious alteration in the interaction between hepatocytes and the ECM during a rapid phase of hepatic growth. In addition, there is an upregulation of many hepatic and non-hepatic molecules. Our aim was to determine whether the expression of DPP IV in liver regeneration is consistent with a role in either binding of hepatocytes to ECM or modification of growth factors. To achieve this we have measured serum DPP IV levels and compared the expression of DPP IV at the protein and mRNA levels in regenerating and sham-operated liver and kidney tissue. This study reports elevated serum DPP IV levels during hepatic regeneration. Serum DPP IV enzyme activity and antigen levels were increased up to 10-fold at 48 h after partial hepatectomy. This followed the same time course as the increase in hepatic DNA replication. There was no significant increase in the serum levels of another bile canalicular enzyme, leucine aminopeptidase. Analysis of hepatic and renal tissue during regeneration showed no detectable increases in DPP IV enzyme or mRNA. The lack of a detectable increase in enzyme and mRNA levels in the kidney or liver suggests other sources for serum DPP IV or increased release of soluble DPP IV from the liver. The increase in serum may be part of a response to control the biological activity of molecules that appear in the blood during the regenerative process.

Zonation of cholesterol and glycerolipid synthesis in regenerating rat livers

Hepatic zonation of cholesterol and glycerolipid synthesis was investigated in regenerating rat livers 24 hr after partial hepatectomy. Tritiated acetate and [U-14C]glycerol were injected into rats' peritoneal cavities for a short-term labeling study. Periportal and perivenous hepatocytes were isolated by digitonin collagenase perfusion. Cholesterol synthesis was significantly higher in periportal hepatocytes of the sham-operated livers (periportal/perivenous = 1.67; p < 0.05). Twenty-four hours after partial hepatectomy, cholesterol synthesis was selectively decreased by 40% (p < 0.01) in periportal hepatocytes. Consequently, hepatic zonation of cholesterol synthesis was abolished in regenerating livers. To study the cholesterol homeostasis on a long-term basis, we substituted deuterated water (25% enriched) for drinking water for 5 days to label newly synthesized cholesterol in a steady state. This procedure clearly demonstrated the net negative cholesterol balance 24 hr after partial hepatectomy. However, the newly synthesized cholesterol contributed equally to the cellular cholesterol pool in both zones. The synthesis of glycerolipids, whether measured from tritiated acetate or [U-14C]glycerol, was significantly increased without apparent zonation in the regenerating livers (twofold increase in phospholipid, and threefold to sevenfold increase in triacylglycerol). We concluded that hepatic zonation of cholesterol synthesis is caused by higher de novo synthesis in periportal hepatocytes, which is abolished in regenerating livers. No zonation of glycerolipid synthesis exists in normal and regenerating livers.

Zonation of cholesterol and glycerolipid synthesis in regenerating rat livers

Hepatic zonation of cholesterol and glycerolipid synthesis was investigated in regenerating rat livers 24 hr after partial hepatectomy. Tritiated acetate and [U- 14C]glycerol were injected into rats' peritoneal cavities for a short-term labeling study. Periportal and perivenous hepatocytes were isolated by digitonin collagenase perfusion. Cholesterol synthesis was significantly higher in periportal hepatocytes of the sham-operated livers (periportal/perivenous = 1.67; p < 0.05). Twenty-four hours after partial hepatectomy, cholesterol synthesis was selectively decreased by 40% (p < 0.01) in periportal hepatocytes. Consequently, hepatic zonation of cholesterol synthesis was abolished in regenerating livers. To study the cholesterol homeostasis on a long-term basis, we substituted deuterated water (25% enriched) for drinking water for 5 days to label newly synthesized cholesterol in a steady state. This procedure clearly demonstrated the net negative cholesterol balance 24 hr after partial hepatectomy. However, the newly synthesized cholesterol contributed equally to the cellular cholesterol pool in both zones. The synthesis of glycerolipids, whether measured from tritiated acetate or [U- 14C]glycerol, was significantly increased without apparent zonation in the regenerating livers (twofold increase in phospholipid, and threefold to sevenfold increase in triacylglycerol). We concluded that hepatic zonation of cholesterol synthesis is caused by higher de novo synthesis in periportal hepatocytes, which is abolished in regenerating livers. No zonation of glycerolipid synthesis exists in normal and regenerating livers.

Uridine diphosphoglucose restores lipocyte proliferation in the regenerating liver of ethanol-treated rats

The effect of continuous intraperitoneal infusion of undine diphosphoglucose on ethanlol-induced suppression of lipocyte proliferation was studied in regenerating rat livers from 1–4 days after hepatectomy. Proliferating lipocytes were positively identified using a two-sequence immunohistochemical staining for cytoplasmic desmin and bromodeoxyuridine-labelled nuclei. Hepatectomy rapidly stimulated lipocyte proliferation which peaked 2 days after hepatectomy (labelling index, 17.9 ± 0.81%). uridine diphosphoglucose or glucose infusion did not modify the time course of lipocyte proliferation. Ethanol feeding to hepatectomized rats receiving saline or glucose infusion resulted in a 71% ( p < 0.005) and 61% ( p < 0.005) inhibition of lipocyte proliferation, respectively, 2 days after hepatectomy, thereby abolishing the characteristic proliferative peak observed in rats not treated with ethanol. In contrast, uridine diphosphoglucose infusion doubled the labelling index (13.1 ± 2.34%) in ethanol-fed rats compared to that in corresponding rats treated with saline (5.28 ± 1.29%; p < 0.005) or glucose (6.51 ± 0.64%; p < 0.005). This resulted in the appearance of a proliferative peak, albeit smaller than normal, 2 days after hepatectomy. In sham-operated rats, lipocyte proliferation was low with a labelling index of 1.88 ± 0.13% at the time of operation and of 1.69 ± 0.23% 2 days thereafter. Uridine diphosphoglucose infusion to sham-operated rats for 2 days did not significantly affect lipocyte proliferation (labelling index 1.79 ± 0.06%). The present study demonstrated that uridine diphosphoglucose does not affect lipocyte proliferation in the regenerating or sham-operated livers, but that it partially reverses the ethanol-induced suppression of lipocyte proliferation after hepatectomy.

Growth-associated changes in fatty acid compositions of nuclear phospholipids of liver cells

To know the possible relationships between nuclear phospholipids and cell proliferation, we have extensively analyzed phospholipids extracted from the nuclei of rat hepatic cells at various growth states. The content of phospholipid in nuclei as well as its composition was similar among liver cells tested, i.e., the regenerating rat livers (28 h, post-hepatectomy), sham-operated or non-treated control livers, and rat ascites hepatoma, AH7974 cells. In contrast, the fatty acid compositions of phospholipids differed from each other among these cells. At the 2-position of phospholipids in the regenerating liver nuclei at 28 h after partial hepatectomy, 18:1 (oleic acid) increased transiently at the expense of 20:4 (arachidonic acid) and 22:6 (docosahexaenoic acid), compared with those in the sham-operated control nuclei. This change in fatty acid composition was commonly observed throughout all phospholipids analyzed, i.e., phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS). On the other hand, the change at 1-position was rather limited: in the regenerating liver nuclei (28 h), 18:1 increased only in PC at the expense of 18:0 (stearic acid). The similar and more marked deviation at the 2-position was observed with AH7974 nuclei it contained approximately 2-times more of 18:1 in PC, PE and PI than regenerating liver nuclei (28 h), and the decreased levels of 20:4 and/or 22:6. It should be noted that there were significant differences in the fatty acid compositions of PE and PS between sham-operated and non-treated controls. So, the sham-operated rat is the appropriate control for proliferation. These results indicate that the increased level of monoenoic fatty acid accompanied by the decreased level of polyunsaturated fatty acid in nuclear phospholipids may be related with cell proliferation.

Transcytotic vesicular carriers for polymeric iga receptors accumulate in rat hepatocytes after bile duct ligation

In rat hepatocytes, transcytotic vesicular carriers transport the mature 120 x 10(3) Mr form of the polymeric IgA receptor (pIgA-R), with or without its ligand, pIgA, from the sinusoidal to the biliary plasmalemma, where the ectodomain of the receptor is cleaved to produce an 80 x 10(3) Mr fragment that is secreted into the bile. Here we show that cholestasis induced by bile duct ligation results in the accumulation of transcytotic carriers, identified by the 120 x 10(3) Mr pIgA-R and pIgA, in the pericanalicular cytoplasm of hepatocytes. To determine the extent of pIgA-R accumulation, hepatic total microsomes (TM) were prepared from control and cholestatic rats. Solubilized TM proteins were separated by SDS-PAGE and receptor forms were detected by immunoblotting and autoradiography. Quantitative densitometry of these autoradiograms showed that after duct ligation the 120 x 10(3) Mr receptor accumulated to a level approximately threefold higher than the control. Concomitantly, immunologically related, novel 124, 90 and 80 x 10(3) Mr proteins (cholestatic antigens) became detectable. Immunoblot analyses of biliary and serum proteins showed that cholestasis resulted in: (1) a marked decrease in the concentrations of the 80 x 10(3) Mr receptor and pIgA in the bile, whereas albumin concentrations remained at control levels; and (2) a marked increase in the concentration of the 80 x 10(3) Mr receptor in the serum. Positive sites for pIgA-R were localized to the pericanalicular cytoplasm of hepatocytes by indirect immunofluorescence on semithin frozen sections in cholestatic hepatocytes. The sites were more numerous and the positive signal stronger than in controls. One day post-ligation, pIgA-positive sites were located to the same pericanalicular cytoplasm of hepatocytes; by three days, however, most pIgA appeared in sinusoidal endothelia and Kupffer cells. To validate the vesicular character of the receptor-positive sites, sham-operated and cholestatic livers were processed for either transmission electron microscopy (TEM) or immunogold localization of receptors on thin frozen sections. TEM verified the accumulation of pericanalicular vesicles in cholestatic hepatocytes. Immunogold tests localized pIgA-R to pleiomorphic, pericanalicular vesicles, which were increased in number, size and concentration of antigenic sites in cholestatic hepatocytes. These findings indicate that bile duct ligation provides a method for manipulating the in vivo transcytotic pathway and for accumulating previously unstudied transcytotic carriers in hepatocytes.

Liver Regeneration Is Associated with Increased Expression of the Insulin-Like Growth Factor-II/Mannose-6-Phosphate Receptor

The process of liver regeneration involves the concerted action of certain growth factors, which stimulate hepatocyte proliferation, and other antiproliferative factors, which prevent uncontrolled growth of this organ. Some of the biological actions of insulin-like growth factor-II (IGF-II), a mitogenic polypeptide closely related to insulin, may be mediated by the IGF-II receptor. This receptor consists of a single chain extracellular domain and a very small cytoplasmic domain, and can bind lysosomal enzymes that contain mannose-6-phosphate (M-6-P) residues. Since these enzymes may be involved in remodelling processes in certain tissues, we measured the expression of the IGF-II/M-6-P receptor in the liver after subtotal hepatectomy. Binding of [125I]IGF-II to crude plasma membranes from regenerating liver was maximal 2 days after hepatectomy (4.9% specific binding/60 micrograms protein) and subsequently decreased. Both control livers (livers removed at the time of operation) and sham-operated control livers demonstrated specific [125I]IGF-II binding of 1.1% throughout the experimental period. This increase in binding in regenerating liver was shown to be associated with an increase in the concentration of IGF-II receptor protein by means of Western blot analysis using a polyclonal anti-IGF-II/M-6-P receptor antiserum (3637). Similarly, steady state levels of IGF-II/M-6-P receptor mRNA, measured by solution hybridization/RNase protection assays, were significantly increased in the regenerating liver (2.0-fold over the control value 2 days after hepatectomy). Five and 10 days postsurgery, the levels of IGF-II receptor mRNA were markedly reduced, and they were even lower than the levels in control livers.(ABSTRACT TRUNCATED AT 250 WORDS)

An activated S6 kinase in regenerating rat liver

S6 kinase activity was increased in the regenerating liver 5 h after partial hepatectomy compared with sham-operated liver. The protein kinase activity was eluted from DE-52 column at approximately 250 mM NaCl and was not affected by known regulators of protein kinases. The S6 kinase was further purified by chromatography on peptide R 1A 13-Sepharose 4B and Sephadex G-150. The molecular weight of the enzyme was estimated to be 4.5 × 10 4 by gel filtration. The enzyme catalyzes the phosphorylation of whole histone, mainly H2B histone, at 75 mM Mg 2+. These properties are similar to those of a proteolytically modified Ca 2+/phospholipid-independent form of protein kinase C.

Effects of mitotic activity and water content on the proton relaxation times in partially hepatectomized and sham-operated rat livers.

Proton relaxation times, T1 and T2, water content, and mitotic activity in control, sham-operated and partially hepatectomized rat livers were measured before surgery, and at 28 hours, 48 hours and six days after surgery. T1, water content, and mitotic activity increased after partial hepatectomy, but T1 was also elevated after sham operations, whereas neither water content nor mitotic activity changed. T2 was unaffected by either procedure. The T1 changed is more likely to be the result of surgery related stress than of changes in water content or growth rate.

Liver regeneration and tumor growth in the rat after partial hepatectomy.

Tumor growth of Yoshida sarcoma implanted in the remnant liver was studied in rats subjected to a hepatectomy. After 70 percent hepatectomy, the liver progressively regenerated and the total liver weight was reverted to by 10 days after the operation. Concomitantly with liver regeneration, tumor growth in the remnant liver was stimulated significantly, compared with that in the sham-operated liver. Incorporation of tritiated thymidine into tumor cells in the remnant liver was strikingly high and progressive, while that in the sham-operated liver was low and retained. Mitomycin C given to the hepatectomized rats was more effective against the tumor in the remnant liver than in the sham-operated liver. We conclude from this study that cancer cell proliferation in the remnant liver can be accelerated by the process of liver regeneration.

Failure to induce selective cholestasis in the rat after long-term extrahepatic selective biliary obstruction.

Forty-eight hours after extra-hepatic selective biliary obstruction (SBO), there is evidence of cholestasis in the obstructed lobes (OL). However, some major ultrastructural features of cholestasis are missing. The aim of this work was to investigate the long-term effect of SBO. One month after surgery, and in comparison with sham-operated rats, bile flow, liver weight, and liver weight ratio of obstructed/nonobstructed lobes were normal. Furthermore, there was no evidence of cholestasis in OL by light and electron microscopy. Bile duct communications between obstructed and non-obstructed lobes were evidenced by Indian ink injection. In sham-operated rats, bile duct communications between ducts of the different lobes were involved in bile drainage. It appears, therefore, that the main reason for the lack of cholestasis 1 month after SBO is the drainage of bile from OL through accessory bile ducts.

Sequence diversity of nuclear and polysomal polyadenylated and non-polyadenylated RNA in normal and regenerating rat liver.

A DNA probe purified from RNA . DNA hybrids of total sham-operated liver RNA and non-repetitive DNA was used to show that nuclear poly(A)-rich RNA from sham-operated liver and from 2.5-h and 48-h regenerating liver contains about 50% of the complexity of total liver RNA. It was further shown that the differences between normal and regenerating liver, reported earlier from this laboratory, occur in the poly(A)-free fraction of nuclear RNA. At the polysome level it was found that polysomal RNA has one-third of the sequence diversity of total RNA and of this, approximately 65% can be accounted for by poly(A)-rich and 55% by poly(A)-free molecules. When DNA probes were prepared from hybrids formed using polysomal RNA from sham-operated liver and regenerating liver at 2.5 h and 48 h post-hepatectomy and then employed in reactions with homologous and heterologous RNAs, no differences were detectable between either normal and regenerating liver or regenerating liver at times during hypertrophy and hyperplasia.

Synthesis in vitro of glycosaminoglycans in regenerating rat liver.

Chronic liver damage is accompanied by both liver cell multiplication and stimulated synthesis of proteoglycans, but the relationship between the two biochemical processes has not been investigated so far. We found that the incorporation of [14C]glucosamine into total glycosaminoglycans of rat liver slices from regenerating tissue is depressed by about 50% 1 and 3 days after operation if referred to that measured in sham-operated control liver slices. 6 h after partial hepatectomy [14C]glucosamine incorporation into glycosaminoglycans is stimulated by more than 30% in relation to sham operated livers. The proportional rates of synthesis of heparan sulfate and chondroitin sulfate (about 8:1) did not change in regenerating liver tissue. Furthermore, there was no difference in the intracellular uptake of [14C]glucosamine by rat liver slices from sham operated and partially hepatectomized rats; the pool size of UDP-N-acetylhexosamine was only slightly larger (about 14%) under the latter experimental condition. We conclude that liver regeneration by itself is not responsible for the elevated production and the changing pattern of proteoglycans in long-lasting hepatic injury.

Albumin messenger RNA after partial hepatectomy and sham operation

Albumin mRNA was quantified in nuclear RNA and in polysomal and post-polysomal poly(A)-containing RNA from untreated, hepatectomized and laparotomized rat livers. A prominent reduction of albumin-specific RNA sequences was observed in all subcellular fractions 50 h after partial hepatectomy, compared to both untreated and sham-operated livers. Surprisingly, laparotomy itself also induced a dilution of albumin-specific sequences at earlier times after operation in nuclei and in post-polysomal supernatant, but not in polysomes.

Base composition studies on transfer RNA from normal and regenerating rat liver

The base composition of bulk tRNA isolated from regenerating rat liver, 12, 18, 24 and 30 h after partial hepatectomy, was determined by a 3H derivative method. Only a few minor statistically significant changes (2–11%), as compared to sham-operated liver, were found at 18, 24 and 30 h after hepatectomy. These included a reduction in the amounts of adenosine and 3-(3-amino-3-carboxypropyl)-uridine, and an increase in the amounts of 1-methyladenosine, 1-methylguanosine, 3-methylcytidine and pseudouridine. Similarly, when the base composition of tRNA fractions from control and 24-h regenerating rat liver, partially purified by one-dimensional polyacrylamide gel electrophoresis, was determined, no gross differences were observed. These results suggest that the process of liver regeneration is not accompanied by a gross alteration of the modification pattern of tRNA.

Fatty acid synthesis in the regenerating liver of the rat.

1. Synthesis de novo of fatty acids in the rat liver, measured per g wet wt. of tissue, was increased by a factor of about two, between 1 and 4 days after partial hepatectomy, compared with rates in sham-operated control rat livers. 2. There were no associated changes in the rates of liver cholesterol synthesis or of adipose-tissue fatty acid synthesis in rats after partial hepatectomy, compared with rates in sham-operated rats. 3. In regenerating livers, perfused under three different conditions, there was no alteration in the capacity for fatty acid synthesis compared with that of control rats. 4. The increased synthesis of fatty acids in regenerating liver was associated with insignificant increases in plasma concentrations of tricylglycerols and free fatty acids, with a decrease in content of liver glycogen, and with no change in hepatic activity of acetyl-CoA carboxylase. 5. The accelerated rate of synthesis of fatty adids in regenerating liver appears not to be due to any intrinsic alteration in hepatic capacity for fatty acid synthesis, but it may be caused by the continuous action on liver of unidentified circulating factors.