scholarly journals THE DISTRIBUTION OF DEOXYRIBONUCLEASE IN NORMAL, CIRRHOTIC AND NEOPLASTIC RAT LIVERS

1959 ◽  
Vol 7 (2) ◽  
pp. 139-143 ◽  
Author(s):  
R. DAOUST ◽  
A. CANTERO

The distribution of deoxyribonuclease in normal, cirrhotic and neoplastic rat livers was investigated histochemically using the gelatine-DNA film method. The bile duct cells and connective tissue elements which are present in abnormal amounts in cirrhotic liver contain little DNAase activity compared with parenchymal tissue. The distribution pattern of DNAase is relatively uniform in normal liver parenchyma but becomes heterogeneous in the parenchyma of cirrhotic and neoplastic tissues. Groups of parenchymal cells in cirrhotic liver and the hepatoma cells in general appear devoid of DNAase activity. The necrotic areas of tissues, on the other hand, show intense enzyme activity.

Hitherto, quantitative investigation of the histology of regenerating liver after partial hepatectomy has been concerned almost entirely with changes in the parenchymal cells. It has long been known, however, that other kinds of cell within the liver take part, and that as a consequence the restored liver is nearly normally organized. A quantitative investigation has therefore been made into the behaviour of different types of cell in regenerating liver. The material consisted of histological sections and tissue cultures of livers of normal adult rats and of adult rats from which two-thirds of the liver had been removed 1, 2, 7 or 21 days previously. Mitosis was found at some stage of the regenerative process in parenchymal cells, bile-duct cells, lining cells of the sinusoids (including v. Kupffer cells), and peritoneal mesothelial cells. While the parenchymal cells showed maximum mitotic rate in the rats killed 1 day after operation, the other types of cel! showed negligible mitosis at this time and maximum mitotic rate at 2 days after operation. At 21 days after operation, the total liver populations of parenchymal cells, sinusoid lining cells and bile-duct cells had all returned to a normal level. In tissue cultures the number of cells appearing outside each explant after 3 days of cultivation was counted. The most important finding was that the explants from the animals killed 2 days after operation produced many more macrophages, fibroblasts and bile-duct cells than the explants from the other animals. Parenchymal cells were not successfully cultured. It is suggested that the results of the tissue cultures indicate changes in the mobility of the cells during regeneration, and that increased mobility may be important in the regenerative process.


Development ◽  
1984 ◽  
Vol 79 (1) ◽  
pp. 25-39
Author(s):  
Nobuyoshi Shiojiri

The origin of the intrahepatic bile ducts in the embryonic mouse liver was investigated. At 12·5 and 13·5 gestation days in the C3H/Tw strain mouse, the liver parenchyma contains morphologically and histochemically homogeneous immature hepatocytes but not bile duct cells. When the liver fragments were cultured in the testis, immature hepatocytes differentiated into large hepatocytes for the most part and also into bile duct cells. In contrast, when the similar liver fragments were cultured under the skin of newborn mice, bile duct cells differentiated much earlier in all transplants than those cultured in the testis. These bile duct cells were considered to be the intrahepatic bile duct cells, since they did not form biliary glands but possessed a basal lamina and histochemical characteristics of intrahepatic bile duct cells of the normal liver. The origin of the endodermal epithelial cells in the mouse liver is discussed with special attention to the differentiation of the intrahepatic bile duct cells from the immature hepatocytes.


1972 ◽  
Vol 20 (7) ◽  
pp. 536-541 ◽  
Author(s):  
R. DAOUST

Films of polyadenylic acid (poly-A) were exposed to liver sections from 4-dimethylaminoazobenzene (DAB)-fed rats in order to determine whether the nucleases acting on these films, like the ribonucleases (RNases), are depressed during carcinogenesis. Normal liver parenchyma gave a positive reaction which was particularly intense in periportal areas. Livers from animals fed the basal control diet showed a similar distribution of enzyme activity but were generally more active than normal livers. In DAB-fed rats, the nodules of hepatic tissue gave intense reactions while the trabeculae of bile ducts and connective tissue, as well as the necrotic areas, were negative. The formation of hyperbasophilic foci at later stages of DAB feeding was accompanied by a loss of enzyme activity. The hepatomas, which apparently derived from such foci, showed weak or negligible activity. Thus the changes in RNases and poly-A hydrolases occur at different stages of the carcinogenic process. The loss of RNase activity precedes the neoplastic transformation while the decrease in the activity of poly-A hydrolases is closely associated with tumor formation, but the induced tumors are deficient in both types of nuclease activity.


1971 ◽  
Vol 123 (5) ◽  
pp. 901-906 ◽  
Author(s):  
F. A. McEvoy ◽  
J. Carroll

1. An enzyme (EC 2.8.2.1) that catalyses the transfer of sulphate from adenosine 3′-phosphate 5′-sulphatophosphate to phenols was purified approx. 2000-fold from male rat livers. 2. The purified preparation did not catalyse the sulphurylation of dehydroepiandrosterone, butan-1-ol, l-tyrosine methyl ester, 1-naphthylamine or serotonin. 3. At pH8.0 and 37°C the Km values of the enzyme for p-nitrophenol and adenosine 3′-phosphate 5′-sulphatophosphate are 51 and 14μm respectively. The Km value for either substrate is independent of the concentration of the other. 4. The sulphurylation of phenol is inhibited by thiol compounds and glutathione at a concentration of 3mm caused an approx. 50% decrease in enzyme activity. 5. The Km of the enzyme for adenosine 3′-phosphate 5′-sulphatophosphate is unaffected by the presence of added glutathione but at a concentration of 5mm-glutathione the Km of the enzyme for its phenolic substrate is decreased.


1992 ◽  
Vol 33 (5) ◽  
pp. 502-503
Author(s):  
G. Tidebrant ◽  
P. Lukes ◽  
A. Wihed

Author(s):  
Sundeep Singh Saluja ◽  
Vaibhav Kumar Varshney ◽  
Vidya Sharada Bhat ◽  
Phani Kumar Nekarakanti ◽  
Asit Arora ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1992
Author(s):  
Max Seidensticker ◽  
Matthias Philipp Fabritius ◽  
Jannik Beller ◽  
Ricarda Seidensticker ◽  
Andrei Todica ◽  
...  

Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 976
Author(s):  
Natalia N. Bezborodkina ◽  
Sergey V. Okovityi ◽  
Boris N. Kudryavtsev

Chronic hepatitises of various etiologies are widespread liver diseases in humans. Their final stage, liver cirrhosis (LC), is considered to be one of the main causes of hepatocellular carcinoma (HCC). About 80–90% of all HCC cases develop in LC patients, which suggests that cirrhotic conditions play a crucial role in the process of hepatocarcinogenesis. Carbohydrate metabolism in LC undergoes profound disturbances characterized by altered glycogen metabolism. Unfortunately, data on the glycogen content in LC are few and contradictory. In this study, the material was obtained from liver biopsies of patients with LC of viral and alcohol etiology and from the liver tissue of rats with CCl4-induced LC. The activity of glycogen phosphorylase (GP), glycogen synthase (GS), and glucose-6-phosphatase (G6Pase) was investigated in human and rat liver tissue by biochemical methods. Total glycogen and its labile and stable fractions were measured in isolated individual hepatocytes, using the cytofluorometry technique of PAS reaction in situ. The development of LC in human and rat liver was accompanied by an increase in fibrous tissue (20- and 8.8-fold), an increase in the dry mass of hepatocytes (by 25.6% and 23.7%), and a decrease in the number of hepatocytes (by 50% and 28%), respectively. The rearrangement of the liver parenchyma was combined with changes in glycogen metabolism. The present study showed a significant increase in the glycogen content in the hepatocytes of the human and the rat cirrhotic liver, by 255% and 210%, respectively. An increased glycogen content in cells of the cirrhotic liver can be explained by a decrease in glycogenolysis due to a decreased activity of G6Pase and GP.


1972 ◽  
Vol 129 (3) ◽  
pp. 645-655 ◽  
Author(s):  
J. S. Heller ◽  
C. L. Villemez

A neutral-detergent-solubilized-enzyme preparation derived from Phaseolus aureus hypocotyls contains two types of glycosyltransferase activity. One, mannosyltransferase enzyme activity, utilizes GDP-α-d-mannose as the sugar nucleotide substrate. The other, glucosyltransferase enzyme activity, utilizes GDP-α-d-glucose as the sugar nucleotide substrate. The soluble enzyme preparation catalyses the formation of what appears to be a homopolysaccharide when either sugar nucleotide is the only substrate present. A β-(1→4)-linked mannan is the only polymeric product when only GDP-α-d-mannose is added. A β-(1→4)-linked glucan is the only polymeric product when only GDP-α-d-glucose is added. In the presence of both sugar nucleotides, however, a β-(1→4)-linked glucomannan is formed. There are indications that endogenous sugar donors may be present in the enzyme preparation. There appear to be only two glycosyltransferases in the enzyme preparation, each catalysing the transfer of a different sugar to the same type of acceptor molecule. The glucosyltransferase requires the continual production of mannose-containing acceptor molecules for maintenance of enzyme activity, and is thereby dependent upon the activity of the mannosyltransferase. The mannosyltransferase, on the other hand, does not require the continual production of glucose-containing acceptors for maintenance of enzyme activity, but is severely inhibited by GDP-α-P-glucose. These properties promote the synthesis of β-(1→4)-linked glucomannan rather than β-(1→4)-linked glucan plus β-(1→4)-linked mannan when both sugar nucleotide substrates are present.


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