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Anabolism versus catabolism of [5-3H]uridine and its relationship to ribonucleic acid labelling in mouse liver after partial hepatectomy.

The balance between anabolism and catabolism of [5-(3)H]uridine was studied in the mouse after partial hepatectomy. Labelling of RNA and UDP-glucose was determined and evaluated in relation to changes in the specific radioactivity of UTP. The amounts of labelled catabolic products of uridine were increased several-fold in liver and blood after partial hepatectomy. The specific radioactivity of RNA decreased to about 60% of the control value at 6h and was in the same range as that of control liver at 24h after operation. Decreased labelling of RNA and UDP-glucose was attributable to decreased specific radioactivity of UTP. No changes in the size of the UTP pool or in the balance between uridine anabolism and catabolism were found that could explain the decreased specific radioactivity of UTP. Rather, the alterations in the labelling of this metabolite induced by the partial hepatectomy may be related to decreased phosphorylating capacity in the liver cells and/or dilution of the labelled precursor in an expanded uridine pool. The enhanced amounts of uridine catabolic products in liver and blood were probably a consequence of accumulation and altered incorporation of the metabolites from the blood into the liver cells. Despite the increased amounts of labelled catabolic products and the decreased labelling of RNA, the results reported here actually suggest decreased uridine catabolism and slightly increased RNA synthesis in mouse liver after partial hepatectomy. The results stress the importance of proper controls in determination of nucleic acid synthesis and in metabolic studies by use of labelled precursors.

Animals↗

Ketone-body metabolism after partial hepatectomy in the rat.

Fed or 24 h-starved rats were subjected to two-thirds partial hepatectomy or sham-operation and subsequently starved for 4, 14 or 24 h. Despite high plasma fatty acid concentrations, the partially hepatectomized rats failed to respond to post-operative starvation with increased blood and liver ketone-body concentrations or to maintain the high ketone-body concentrations associated with pre-operative starvation. Hypoglycaemia and hyperlactaemia were observed within 30 min of functional hepatectomy, but not partial hepatectomy, of 24 h-starved rats, and, even after a further 24 h starvation of partially hepatectomized rats, blood glucose concentrations were only slightly decreased. The results are discussed with reference to fat oxidation and gluconeogenesis in the liver remaining after partial hepatectomy.

Animals↗

Estimation of prognosis after hepatectomy for hepatocellular carcinoma.

BACKGROUND: The preferred means of treatment for hepatocellular carcinoma is surgical resection. However, the tumour recurrence rate is high. Accurate estimation of the risk of tumour recurrence after hepatectomy may facilitate the administration of adjuvant therapy after hepatectomy to patients with a high likelihood of tumour recurrence. METHODS: The clinical and pathological profiles of 176 patients undergoing hepatectomy for hepatocellular carcinoma from March 1992 to August 1998 were reviewed. The Kaplan--Meier method and log rank test were used to analyse univariate prognostic factors. The Cox proportional hazard model was used for multivariate analysis. Disease-free and overall cumulative survival rates were estimated with respect to the number of prognostic factors. RESULTS: Independent factors associated with a lower disease-free survival included the presence of venous infiltration, presence of daughter tumours, absence of tumour encapsulation and tumour size exceeding 5 cm. Factors decreasing the overall survival rate included the presence of venous infiltration, absence of tumour encapsulation and surgical resection margin less than 1 cm. The 1-year disease-free survival rate decreased from 77.5(s.e. 5.6) to 14.0(8.5) per cent when the number of risk factors present increased from zero to three. The 5-year survival rate decreased from 60.2(11.7) per cent to zero when the number of risk factors increased from zero to three. CONCLUSION: The deterioration of disease-free or overall survival of patients with hepatocellular carcinoma after hepatectomy correlates with increasing number of risk factors. The number of risk factors can be employed to accurately estimate disease-free and overall survival.

Carcinoma, Hepatocellular↗

Role of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats.

BACKGROUND AND AIMS: The authors have shown previously that sinusoidal endothelial cell injury developed concomitantly with the accumulation of neutrophils in the hepatic sinusoidal space in cholestatic rats after extensive hepatectomy. The aim of the present study was to investigate the role of neutrophils in the development of this kind of endothelial cell injury. METHODS: Rats underwent 78% partial hepatectomy after 2 weeks of cholestasis, and subsequent external biliary drainage for 5 days. To decrease the number of neutrophils, antirat neutrophil serum was administered intraperitoneally. Some serum parameters and histological specimens were examined 48 h after partial hepatectomy. RESULTS: Anti-neutrophil serum significantly reduced the number of accumulated neutrophils in the hepatic sinusoids. Although the purine nucleoside phosphorylase: alanine aminotransferase ratio, a marker of non-parenchymal cell injury, was increased in cholestatic-hepatectomized rats, this abnormality was significantly attenuated by the treatment with antineutrophil serum. Electron microscopically, focal detachment of cytoplasms of sinusoidal endothelial cells was observed occasionally in cholestatic-hepatectomized rats, but was not found in the antirat neutrophil serum-treated rats. CONCLUSION: These results indicate that accumulated neutrophils might be important effector cells in the pathogenesis of sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats, even after appropriate external biliary drainage.

Alanine Transaminase↗

Estrogen therapy for hepatectomy patients with poor liver function?

Estrogen is well known to promote liver regeneration after partial hepatectomy. Administration of estradiol prior to partial hepatectomy also induces increased activity of DNA synthesis. Endogenous aromatase plays a key role in the conversion of testosterone to estradiol. The aromatase activity was induced by IL-6, which is a key factor for liver regeneration. It has been reported that IL-6 interacts with gp80/130 receptor and regulates the STAT1/3 pathway to induce DNA synthesis in hepatocyte. The IL-6 induced aromatase activity results in increased serum estradiol level. This corresponded well with observation that estradiol was elevated after partial hepatectomy. Therefore, it is very likely that estradiol and IL-6 synergize in stimulation of hepatocyte proliferation during liver regeneration. We propose that a short-term estradiol treatment may be beneficial for patients with poor liver function after hepatectomy.

Animals↗

Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma.

BACKGROUND: Resection of hepatocellular carcinoma is associated with high rates of morbidity and mortality. Since intensive nutritional support can reduce the catabolic response and improve protein synthesis and liver regeneration, we performed a prospective study to investigate whether perioperative nutritional support could improve outcome in patients undergoing hepatectomy for hepatocellular carcinoma. METHODS: We studied 124 patients undergoing resection of hepatocellular carcinoma. Sixty-four patients (39 with cirrhosis, 18 with chronic active hepatitis, and 7 with no associated liver disease) were randomly assigned to receive perioperative intravenous nutritional support in addition to their oral diet, and 60 patients (33 with cirrhosis, 12 with chronic active hepatitis, and 15 with no associated liver disease) were randomly assigned to a control group. The perioperative nutritional therapy consisted of a solution enriched with 35 percent branched-chain amino acids, dextrose, and lipid emulsion (50 percent medium-chain triglycerides) given intravenously for 14 days perioperatively. RESULTS: There was a reduction in the overall postoperative morbidity rate in the perioperative-nutrition group as compared with the control group (34 percent vs. 55 percent; relative risk, 0.66; 95 percent confidence interval, 0.45 to 0.96), predominantly because of fewer septic complications (17 percent vs. 37 percent; relative risk, 0.57; 95 percent confidence interval, 0.34 to 0.96). There were also a reduction in the requirement for diuretic agents to control ascites (25 percent vs. 50 percent; relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.87), less weight loss after hepatectomy (median loss, 0 kg vs. 1.4 kg, P = 0.01), and less deterioration of liver function as measured by the change in the rate of clearance of indocyanine green (-2.8 percent vs. -4.8 percent at 20 minutes, P = 0.05). These benefits were seen predominantly in the patients with underlying cirrhosis who underwent major hepatectomy. There were five deaths during hospitalization in the perioperative-nutrition group, and nine in the control group (P not significant). CONCLUSIONS: Perioperative nutritional support can reduce complications after major hepatectomy for hepatocellular carcinoma associated with cirrhosis.

Adult↗

Timing of hepatocyte entry into DNA synthesis after partial hepatectomy is cell autonomous.

After surgical removal of two-thirds of the liver, remaining hepatocytes replicate and restore hepatic mass within 2 weeks. This process must be initiated by signals extrinsic to the hepatocyte, but it remains unclear whether subsequent events leading to DNA synthesis (S phase) are regulated by circulating or locally produced growth factors (a noncell autonomous response), or by a program intrinsic to the hepatocyte itself (a cell autonomous response). To identify the type of mechanism regulating passage to S, we exploited the difference between rat and mouse hepatocytes in the timing of DNA synthesis after partial hepatectomy, which peaks 12-16 h earlier posthepatectomy in rat compared with mouse. Four groups of animals received two-thirds partial hepatectomies: rats, mice, mice with chimeric livers composed of both transplanted rat hepatocytes and endogenous mouse hepatocytes, and mice with chimeric livers composed of both transplanted and endogenous mouse hepatocytes. Following two-thirds partial hepatectomy, both donor and endogenous hepatocytes in mouse/mouse chimeric livers displayed kinetics of DNA synthesis characteristic of the mouse, indicating that transplantation per se did not affect the response to subsequent partial hepatectomy. In contrast, rat hepatocytes in chimeric mouse livers displayed rat kinetics despite their presence in a mouse host. Thus, factors intrinsic to the hepatocyte must regulate the timing of entry into DNA synthesis. This result defines the process as cell autonomous and suggests that locally or distantly produced cytokines or growth factors may have a permissive but not an instructive role in progression to S.

Animals↗

Changes of serum and urinary neopterin concentrations in rats after partial hepatectomy.

OBJECTIVE: To investigate the changes in serum and urinary neopterin concentrations over time after partial hepatectomy in rats, and to find out if neopterin can be used as a marker of immunological response during the regulation of liver regeneration. DESIGN: Randomised experiment. SETTING: University hospital, Taiwan, R.O.C. SUBJECTS: 84 male Wistar rats weighing about 200g. INTERVENTIONS: Partial hepatectomy (67%) or sham operation (n = 42 in each group). MAIN OUTCOME MEASURES: Serum and urinary neopterin concentrations measured by radioimmunoassay preoperatively and on days 1, 2, 3, 5, 7, and 10 postoperatively. RESULTS: Serum neopterin concentrations increased and reached their peak on days 5 and 7 after partial hepatectomy. The urinary neopterin concentration showed a similar trend, but with a more pronounced increase on days 5 and 7. CONCLUSIONS: Serum and urinary neopterin concentrations can be used as markers of activated cell-mediated immunity in rats after partial hepatectomy.

Animals↗

The changes in glycosylation after partial hepatectomy enhance collagen binding of vitronectin in plasma.

Vitronectin is a multifunctional glycoprotein present in the extracellular matrix and plasma. Changes in rat vitronectin were studied during liver regeneration after partial hepatectomy. Carbohydrate concentrations of vitronectin decreased to 2/3 of sham-operated rats at 24 h after partial hepatectomy. Carbohydrate composition and lectin reactivity indicated that N-glycosylation and sialylation of vitronectin changed markedly after partial hepatectomy, while amino acid composition did not change significantly. We previously showed that deN-glycosylation of vitronectin in vitro affects collagen binding among various ligands (Yoneda et al., Biochemistry (1998) 37, 6351-6360). Vitronectins from partially hepatectomized rats at 24 h were found to exhibit markedly enhanced binding to type I collagen. The effect of sialylation on collagen binding was further examined using enzymatically deglycosylated vitronectin of nonoperated rats. Collagen binding increased by 1.2 times after deN-glycosylation of vitronectin, while it increased more than 2.9 times after desialylation. Various glycosyltransferases in liver are known to change after partial hepatectomy, including the attenuation of N-oligosaccharide transferase. The findings therefore suggest that the collagen binding of vitronectin is modulated by the alteration of peptide glycosylation caused by postoperative physiological changes of glycosyltransferases and that the change may contribute to tissue remodeling processes.

Amino Acids↗

Insulin requirements for hepatic regeneration following hepatectomy.

On the basis of changes in the adenine nucleotide the mitochondrial metabolism of the remnant liver, insulin requirements for hepatic regeneration were studied in diabetic rats treated with varying amounts of alloxan. Mildly diabetic rats with less than 30% inhibition in maximal portal insulin response to oral glucose load, showed a parabolic glucose tolerance pattern and could tolerate partial hepatectomy. Whereas, severely diabetic rats with more than 45% inhibition showed a linear glucose tolerance pattern and died within 24 hours after partial hepatectomy. In the former rats, the energy charge (ATP + 1/2ADP/ATP + ADP + AMP) levels of the remnant liver decrease slightly at an early period after partial hepatectomy but could be restored rapidly to normal levels with a concomitant rise of oxidative phosphorylation in remnant liver mitochondria. In contrast, the energy charge levels in the latter groups fell more markedly and could not be restored, because of insufficient enhancement of mitochondrial oxidative phosphorylation. It is suggested that an enhancement in mitochondrial phosphorylative activity of the remnant liver following partial hepatectomy is inhibited in proportion to the severity of impaired insulin secretion, resulting in a decrease of the potential functional capacity of liver.

Adenine Nucleotides↗

Effect of total hepatectomy and administration of branched-chain amino acids on regional norepinephrine, dopamine, and amino acids in rat brain.

In rats after total hepatectomy, the effect of infusing glucose alone or combined with branched-chain amino acids on amino acid concentrations in plasma and cerebral cortex and on catecholamine levels in eight different regions of the brain was studied. Infusion of branched-chain amino acids reduced the accumulation of tryptophan, phenylalanine, and tyrosine in plasma, while in cerebral cortex, the concentrations of phenylalanine and tyrosine were normalized and that of tryptophan was reduced greatly. In rats with hepatectomy and glucose infusion alone, norepinephrine levels were decreased in seven of eight brain regions with the exception of striatum, while dopamine was reduced significantly in striatum only. Infusion of branched-chain amino acids resulted in higher norepinephrine in cortex, mesencephalon, and hypothalamus and higher striatal dopamine 18 hours after hepatectomy. Thus, infusing branched-chain amino acids and reducing the accumulation of various neutral amino acids in brain may partially prevent the loss of norepinephrine from brain after total hepatectomy.

Amino Acids, Branched-Chain↗

Significant influence of accompanying chronic hepatitis status on recurrence of hepatocellular carcinoma after hepatectomy. Result of multivariate analysis.

OBJECTIVE: The aim of this study was to evaluate the correlation between the histologic status of accompanying chronic hepatitis and the recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy by multivariate analysis. SUMMARY BACKGROUND DATA: Recent studies have suggested that a considerable number of intrahepatic recurrence of HCC after hepatectomy might be the results of metachronous multicentric hepatocarcinogenesis. The authors hypothesized that the incidence of recurrence due to metachronous multicentric hepatocarcinogenesis would depend on the histologic status of accompanying chronic viral liver disease, which is a main promoter of HCC. METHODS: One hundred ten patients with HCC who underwent curative resection were studied. Histologic status of accompanying chronic hepatitis was classified into the three categories: 1) normal liver or chronic persistent hepatitis (CPH, n = 13), 2) chronic aggressive hepatitis (CAH, n = 50), and 3) liver cirrhosis (LC, n = 47). RESULTS: The Cox multivariate proportional hazard model showed that the accompanying chronic viral hepatitis status (p = 0.0133), extent of hepatectomy (p = 0.0078), and number of tumors (p = 0.0475) were significantly predictive variables for recurrence-free survival. By the log-rank test, recurrence-free survival rate in patients with CPH was significantly higher than those in patients with CAH (p = 0.0005) and LC (p = 0.0075). Patients with CAH had the lowest recurrence-free survival rate (vs. LC, p = 0.028). CONCLUSIONS: The results of this study indicated the significant influence of histologic activity of hepatitis on recurrence of HCC. This might support the concept of significant contribution of multicentric hepatocarcinogenesis to recurrence of HCC after hepatectomy.

Adult↗

Right portal vein embolization before right hepatectomy for unilobar colorectal liver metastases reduces the intrahepatic recurrence rate.

AIM: To assess the effect of portal vein embolization (PVE) on intrahepatic recurrence rate after right hepatectomy for unilobar colorectal liver metastases (CLM). SUMMARY AND BACKGROUND: Recent research suggests that CLM could spread retrogradely through the portal vein. PVE may reduce tumor shedding by the occlusion of distal portal branches. However, no study reported the clinical effect of PVE on intrahepatic recurrence after CLM resection. PATIENTS AND METHODS: Between 1995 and 2003, 44 patients requiring a right hepatectomy for unilobar CLM were operated in our institution. Right hepatectomy was performed after PVE in 23 patients (group A) and without PVE in 21 (group B). Surgical outcome and site of recurrence were analyzed. RESULTS: The postoperative mortality was nil. Overall morbidity and transitory liver failure rates were similar in groups A and B (43.4% and 17.3% vs. 33.3% and 14.2%, respectively). The 3- and 5-year overall survival rates did not differ in group A and B patients (61.2% and 43.7% vs. 49.7% and 35.5%, respectively; P = 0.862). The disease-free survival rate was similar in both groups. Thirty patients (68.2%) developed recurrences. Recurrences were intrahepatic in 22 patients (50%) and extrahepatic in 27 (61.3%). Intrahepatic recurrence rate was significantly lower in group A compared with group B (26.0% vs. 76.1% respectively; P < 0.001). PVE, number of CLM, and administration of neoadjuvant chemotherapy were independent prognostic factors for intrahepatic recurrences. CONCLUSION: This study showed that PVE reduces intrahepatic recurrence rate after right hepatectomy for unilobar CLM.

Adult↗

Marginal hepatectomy in the rat: from anatomy to surgery.

OBJECTIVE: Based on the 3-dimensional visualization of vascular supply and drainage, a vessel-oriented resection technique was optimized. The new surgical technique was used to determine the maximal reduction in liver mass enabling a 50% 1-week survival rate. BACKGROUND DATA: Determination of the minimal liver mass is necessary in clinical as well as in experimental liver surgery. In rats, survival seems to depend on the surgical technique applied. Extended hepatectomy with removal of 90% of the liver mass was long regarded as a lethal model. Introduction of a vessel-oriented approach enabled long-term survival in this model. METHODS: The lobar and vascular anatomy of rat livers was visualized by plastination of the whole organ, respectively, by corrosion casts of the portal vein, hepatic artery and liver veins. The three-dimensional models were used to extract the underlying anatomic structure. In 90% partial hepatectomy, the liver parenchyma was clamped close to the base of the respective liver lobes (left lateral, median and right, liver lobe). Piercing sutures were placed through the liver parenchyma, so that the stem of portal vein and the accompanying hepatic artery but also the hepatic vein were included. RESULTS: A 1-week survival rate of 100% was achieved after 90% hepatectomy. Extending the procedure to 95% resection by additional removal of the upper caudate lobe led to a 1-week survival rate of 66%; 97% partial hepatectomy, accomplished by additional resection of the lower caudate lobe only leaving the paracaval parts of the liver behind, resulted in 100% lethality within 4 days. CONCLUSIONS: Using a anatomically based, vessel-oriented, parenchyma-preserving surgical technique in 95% liver resections led to long-term survival. This represents the maximal reduction of liver mass compatible with survival.

Animals↗

Toward current standards of donor right hepatectomy for adult-to-adult live donor liver transplantation through the experience of 200 cases.

OBJECTIVE: To define the current standards of donor right hepatectomy, including the middle hepatic vein for adult-to-adult live donor liver transplantation. SUMMARY BACKGROUND DATA: Donor morbidity and mortality are inevitable given the ultra-major nature of the donor operation. Results from a matured center could define the true impact of this donor procedure most accurately. PATIENTS AND METHODS: From May 9, 1996 to April 13, 2005, 200 consecutive donors underwent donor right hepatectomy at the University of Hong Kong Medical Center. All right liver grafts except one included the middle hepatic vein. Donor characteristics, operation time, blood loss, hospital stay, laboratory results, and complications graded by Clavien's classification divided into four eras (each consecutive 50 cases) were compared. RESULTS: Donor characteristics of the four eras were generally comparable. Operative outcomes improved progressively through the four eras. From era 1 to era 4, operation time decreased from 598 minutes (range, 378-932 minutes) to 391 minutes (range, 304-635 minutes). Blood loss also decreased from 500 mL (200-1600 mL) of era 1 to 251 mL (range, 95-595 mL) of era 4. Overall complication rate was 20.5% (41 of 200). Complications rates from eras 1 to 4 were 34%, 16%, 16%, and 16%, respectively. The most common complications were of grade I (24 of 41, 58.5%). A late donor death occurred in era 4 from the development of a duodenocaval fistula 10 weeks postoperation, giving a donor mortality of 0.5% (1 of 200). CONCLUSIONS: This study validated the estimated morbidity and mortality of donor right hepatectomy of 20% and 0.5%, respectively. The data provide reference for counseling potential donors and setting the standards of donor right hepatectomy in the current era.

Adolescent↗

Urinary matrix metalloproteinases and their endogenous inhibitors predict hepatic regeneration after murine partial hepatectomy.

BACKGROUND: Matrix metalloproteinases (MMPs) play a key role in extracellular matrix remodeling events associated with hepatic regeneration after partial hepatectomy. We therefore hypothesized that urinary MMPs and their endogenous tissue inhibitors of matrix metalloproteinases (TIMPs) might also provide important information regarding initiation and progression of liver regeneration. METHODS: Groups of 20 mice underwent sham operations, two-thirds hepatectomy, or treatment with the angiogenesis inhibitor, AGM-1470,O-chloroacetyl-carbamoyl-fumagillol (TNP-470), after two-thirds hepatectomy to prevent hepatic regeneration. Urine was collected preoperatively and for 24 days after surgery and tested for MMP-2, MMP-9, TIMP-1, and TIMP-2 using substrate gel electrophoresis (zymography) and Western blot analysis. RESULTS: During hepatic regeneration, MMP-9 was detected in the urine at significantly lower levels on postoperative day 8 when the liver returned to its preoperative mass. In contrast, urine from mice whose livers were inhibited from regenerating (TNP-treated groups) contained increased levels of the gelatinases MMP-2 and MMP-9. The MMP inhibitors, TIMP-1 and TIMP-2, were significantly reduced in the urine of mice with normally regenerating livers but were increased in the urine of mice treated with TNP-470 on day 8. CONCLUSIONS: We demonstrate that (1) urinary MMPs and their cognate inhibitors, the TIMPs, can be detected in the urine of mice undergoing partial hepatectomy, (2) the presence of these remodeling proteins in the urine may predict the progressive return of the partially resected liver to its preoperative mass, and (3) analysis of urinary MMPs and TIMPs may someday provide a noninvasive means of monitoring the status of patients undergoing hepatic resection and transplantation.

Angiogenesis Inhibitors↗

Effect of double partial hepatectomies at various intervals on [3H]thymidine incorporation into rat liver DNA.

At various intervals after a 34% hepatectomy, another 34% (50% of the remnant) hepatectomy was performed on rats, and the [3H]thymidine incorporation into the DNA of remaining liver cells was measured 24 hr after the first operation. The values of [3H]thymidine incorporation into liver DNA of rats hepatectomized doubly (34% and 34%) at 6, 8 and 10 hr intervals were greater than the sum of the value of rats which received a single 34% hepatectomy at the start and those of rats which received a single 68% hepatectomy at 6, 8 and 10 hr, respectively.

Animals↗

The efficiency of nuclear processing of the tyrosine aminotransferase mRNA transcript increases after partial hepatectomy.

Following a two-thirds partial hepatectomy, an approximately fivefold increase in the levels of nuclear and total mRNA for tyrosine aminotransferase was observed at 1 h and 1.5 h, respectively, and a return to the levels of the quiescent state, i.e. the levels found in non-operated livers from adrenalectomized rats, was established 16 h post-hepatectomy. The increase in mRNA levels was not accounted for by a comparable change in the rate of transcription of the gene which, at 0.5 h post-hepatectomy, reached a maximum value that amounted to only 1.4-fold the value for quiescent liver. Subsequent changes in the transcription rate largely accounted for the changes in mRNA levels observed later on. Although tyrosine aminotransferase mRNA levels were equal in quiescent and 16-h-regenerating liver, the rate of transcription of the gene in quiescent liver was threefold higher than the rate in 16-h-regenerating liver. The maintenance of a higher rate of gene transcription in quiescent liver, as compared to regenerating liver, was shown to depend on ongoing protein synthesis. The possibility that the high rate of gene transcription was due to blockage or pausing during transcript elongation in quiescent liver was excluded. The inference is that the pronounced increase in tyrosine aminotransferase mRNA levels within 1 h of partial hepatectomy is largely due to a rapid increase in the efficiency of nuclear processing of the primary transcript.

Animals↗