Compartmentation of purine and pyrimidine nucleotides in animal cells.
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Animals↗
Biomedical subjects
U Stenram
Publications and source records attributed to U Stenram.
Effects of the specific cholecystokinin antagonist L 364,718 in experimental acute pancreatitis in the rat.
Cholecystokinin (CCK) has been suggested to be involved in the pathogenesis of acute pancreatitis. To test this hypothesis, we administered the highly selective and specific CCK receptor antagonist L 364,718 to rats in which acute experimental pancreatitis had been induced by the use of transduodenal pancreatic duct injection of taurocholate. It was, however, found that despite the use of L 364,718 at a high dose level (1 mg/kg body weight given three times), and also given prior to induction of pancreatitis, the mortality rate, the serum or ascites amylase activity, the pancreatic concentrations of lysosomal enzymes or the morphology of the pancreas were not affected. This suggests that the CCK receptors are not involved in the pathogenesis of acute pancreatitis in this experimental model, and, consequently, that CCK receptor antagonists have no place in the therapy of this condition.
Acute Disease↗
Hepatic artery administration of degradable starch microspheres: II. Effects on incorporation of uridine and uracil into RNA of an adenocarcinoma transplanted to rat liver.
Effects of degradable starch microspheres administered via the hepatic artery were examined in rats in which an adenocarcinoma was transplanted into the liver. 3H-uridine or 3H-uracil with cold uridine and uracil, respectively, in amounts corresponding to therapeutic doses of these two pyrimidines as fluoro compounds, were administered with or without microspheres. Labeling of the acid-soluble fraction and RNA of tumor, liver, small intestine, spleen, kidney, and bone marrow was examined after 3 and 60 min after injection. When microspheres were added, the specific radioactivity of tumor RNA was significantly higher at both 3 min (P less than 0.05) and 60 min (P less than 0.01) in the rats given uridine, and in rats given uracil it was higher at 60 min after injection (P less than 0.05). There were no such differences in the labeling of the normal tissues. The results indicate that arterial administration of cytostatic drugs, such as 5-fluoropyrimidines, together with degradable starch microspheres might increase the cytotoxic effect on tumors nourished by the artery.
Adenocarcinoma↗
Variation of incorporation of [3H]orotic acid into the nucleotide and RNA fractions of different parts of the same liver lobe in the rat.
1. Anaesthetized rats were given [3H]orotic acid either intraperitoneally or via a catheter into the hepatic artery with or without degradable starch microspheres. 2. The radioactivity in the acid soluble and RNA fractions of five pieces of the left lateral liver lobes was determined. 3. A variation of the distribution of the precursor into the different parts of the same liver lobe was shown. 4. This variation was most pronounced (3000-17,000 cpm/micrograms in the acid soluble fraction) when the precursor was administered via the artery and without microspheres. 5. The correlation between the radioactivity in the acid soluble and RNA fractions within each liver piece was 0.85, 0.90 and 0.75 in the three groups respectively. 6. It is suggested that the variation of the distribution depends on circulatory differences within the liver.
Animals↗
Isotachophoretic and HPLC determination of nucleotides in rat liver cell nuclei isolated by non-aqueous technique.
Rat liver whole cells and cell nuclei were prepared by a non-aqueous technique (glycerol). The nuclear preparations were of different purity as determined by RNA/DNA ratios (0.17-1.60) and accordingly were divided into 3 subgroups (mean values 0.29, 1.04 and 1.48). RNA nucleotides were separated by isotachophoresis and HPLC and calculated per mg DNA. Two of the nuclear subgroups (RNA/DNA = 1.04 and 1.48) had significantly elevated nucleotide values in relation to RNA/DNA. UDP-N-acetylhexosamine/DNA, on the contrary, was reduced in conformity with RNA in the preparations. Our findings may indicate different nucleotide concentrations in different parts of the cell.
Adenine Nucleotides↗
5-Fluorouracil incorporation into RNA of a rat liver adenocarcinoma after hepatic artery injection together with degradable starch microspheres.
The effect of degradable starch microspheres (DSM) on the cellular incorporation of 5-fluorouracil (FUra) was studied in rats with solitary liver tumours. 3H-labelled FUra [0.78 mg (6000 nmol)/kg b.wt.] was injected with saline or mixed with DSM, into the hepatic artery. Labelling of the acid soluble fraction (ASF), RNA and DNA of tumour, liver, bone marrow and small intestine was measured 60 minutes after injection. The DSM had no significant effect on the incorporation of FUra into the ASF or RNA, neither in tumour nor liver tissue. Regarding the tumour/normal tissue ratios of specific radioactivities, there was with DSM a higher tumour/liver and a higher tumour/bone marrow ratio in the ASF, indicating an increased tumour drug exposure with DSM. However, this was not accompanied by any significant increase in drug anabolism.
Adenocarcinoma↗
Ultrastructural diagnosis in the immotile cilia syndrome.
This article reports on the experience with 38 biopsies from nasal mucosa, submitted with the question of immotile cilia syndrome. Fixation in glutaraldehyde with MgSO4 is preferable. At least 50 cilia should be scrutinized in the electron microscope, and dynein arms, radial spokes, sheaths, nexin links and orientation should be tabulated. Six cases displayed virtual absence of inner and outer dynein arms. The orientation of these cilia was random. Two of the patients had situs inversus. In biopsies considered not to represent the immotile cilia syndrome, about four inner and seven outer dynein arms were found per cilium.
Adolescent↗
Effects of administration routes on the uptake of uridine and 5-fluorouridine into an adenocarcinoma transplanted to rat liver.
In a model of secondary liver cancer in Wistar rats, the effect of different administration routes on the uptake of 3H-uridine into tumor and several normal tissues was studied. The rats were inoculated with a tumor cell suspension in the central liver lobe. Ten days later, they were distributed into four groups with a catheter placed in the gastroduodenal artery, the portal vein, one of the femoral veins, or in the peritoneal cavity. 3H-uridine was injected 46 h later and after an additional 90 minutes the animals were anesthetised and pieces of liver tumor and normal tissues were removed and frozen. The incorporation into the acid-soluble fraction and RNA was analyzed. In a separate experiment, 3H-fluorouridine was administered by the gastroduodenal artery and a comparison was made with the uptake of 3H-uridine. A significantly higher amount of uridine was incorporated into the tumor by the arterial route. The intraportal and intraperitoneal routes were comparable, while a somewhat higher incorporation was found by the systemic route. The consequences of using the different routes upon the incorporation into RNA of tumor and dose-limiting organs are demonstrated. With the aid of this experimental model, it is possible to evaluate further the effect by different manipulations on different drugs regarding the administration route.
Adenocarcinoma↗
Splenic mesothelial cysts at laparoscopy.
One case of splenic mesothelial cyst formation fortuitously found and biopsied during laparoscopic operation is described.
Adult↗
Effect of hepatic artery ligation on the incorporation of 3H-orotic acid into an adenocarcinoma transplanted to rat liver.
In the model of secondary liver cancer in Wistar rats a study was made of the influence of hepatic artery ligation (HAL) on the amount of nucleotides and RNA in tumor and liver tissue and on the uptake of 3H-orotic acid into these compounds and DNA after labelling for 90 minutes. Ten days after inoculation with tumor cells into the central liver lobe, a catheter was placed into the portal vein in all rats and in half of them the hepatic artery was ligated. On days one, three, five or ten, rats were given 3H-orotic acid through the catheter. On day ten 3H-orotic acid was also infused via the femoral vein or intraperitoneally. After HAL there was a decrease in the nucleotide and RNA content of the tumor cells after one, three and five days. There was no such decrease in the liver cells. In all HAL rats there was an increase in the nucleotide and RNA content of the tumor cells at day ten compared to day five. The ratio of RNA to acid soluble fraction labelling in tumors was also increased on day ten in all groups compared to HAL rats at day five. The increased uptake of 3H-orotic acid into tumour RNA at day ten after HAL strongly suggests rearterialization. There was no support for an increased vascularization of the tumor from the portal vein on day three or five. In the liver tissue, HAL had no influence. This experimental study gives no support for the use of hepatic dearterialization followed by intraportal infusion av cytostatic agents in clinical settings.
Adenocarcinoma↗
Incorporation of pyrimidines and 5-fluoropyrimidines into normal tissues and an adenocarcinoma transplanted into the liver in rat.
In a model of secondary liver cancer in Wistar rats, the incorporation of tracer doses of pyrimidines and 5-fluoropyrimidines into the acid-soluble fraction, RNA and DNA of several normal tissues and of an experimental adenocarcinoma of the colon transplanted to the liver of rat was determined 90 min after infusion of the substances via the gastroduodenal artery. There was a higher incorporation after injection of FUra than after uracil into tumor RNA. There was very little labeling of DNA by FdUrd but a greater labeling of RNA following injection of this substance than following deoxyuridine in all tissues including tumor except in liver, where it was of the same magnitude. All fluoro compounds gave high labeling of the acid-soluble fraction of the kidney and liver. The experiments will be continued with therapeutic doses of the fluoro compounds.
Adenocarcinoma↗
Hepatic artery administration of degradable starch microspheres. I. Effect on energy charge and incorporation of precursors into rat liver nucleic acids.
The effects of hepatic artery administration of degradable starch microspheres on liver energy charge and nucleic acid anabolism were studied in rats. Liver energy charge was evaluated 20 and 60 min after the injection of degradable starch microspheres. As compared to controls the microspheres had no effect on liver energy charge. The incorporation of orotic acid, uracil, and thymidine into liver RNA or DNA was studied 1 h after hepatic artery injection of precursor alone or together with degradable starch microspheres. Orotic acid and uracil incorporation into RNA was studied in normal rats and the DNA incorporation of thymidine in animals with regenerating livers. Orotic acid and thymidine were given in trace amounts. Uracil was given in amounts corresponding to a therapeutic dose of 5-fluorouracil. The addition of microspheres had no effects on the incorporation of the nucleic acid precursors into RNA or DNA. Thus, in the normal liver degradable starch microspheres administered by the hepatic artery had no influence on liver energy charge or RNA anabolism in the liver. Also the microspheres had no negative effects on the DNA anabolism in proliferating liver cells.
Animals↗
Local hyperthermia in treatment of experimental liver tumors.
An experimental model for local microwave hyperthermia treatment of liver tumors is presented. Fifty-four Wistar rats were inoculated with a transplantable adenocarcinoma (NGW) in the central liver lobe. Ten to 16 days later 28 of the rats were exposed to local hyperthermia. A master thermistor placed in the liver parenchyma adjacent to the tumor controlled the hyperthermia, and the tumor-bearing liver lobe was maintained at 42.0 degrees C for 1 hour. At laparotomy 7 days after treatment, the tumor volume was measured. Four weeks after tumor inoculation, autopsy was performed. The tumor and the surrounding parenchyma was excised for histopathologic examination. A statistically significant reduction in tumor growth was found after exposure to local hyperthermia, the effect of hyperthermia being most pronounced in moderate-sized tumors (300-500 mm3 or 0.5-0.75 g). In larger tumors (greater than 900 mm3 or greater than 1.1 g) extensive necrosis developed after hyperthermia treatment. This indicates good tumoricidal effect even in large tumors, although this is not obvious if reduction in tumor growth is used as the only parameter to evaluate the effect of hyperthermia.
Adenocarcinoma↗
Influence of a reticuloendothelial-suppressing agent on liver tumor growth in the rat.
Reticuloendothelial (RE) function was evaluated by measuring the biokinetics of a standardized 99Tcm-sulphur colloid. Methyl palmitate was administered intravenously on two consecutive days. A statistically significant reduction in the colloid uptake rate of the liver was registered after methyl palmitate administration. Histological examination revealed no signs of destruction of RE cells or microembolization. Inoculation of an experimental nitrosoguanidine-induced transplantable adenocarcinoma to the liver was performed in 16 rats one day after methyl palmitate administration and in 16 controls. Tumor size was significantly larger in methyl-palmitate-treated animals at 7 and 14 days after inoculation. Survival was significantly decreased in methyl-palmitate-treated rats. These rats showed signs of fatty vacuolization and necrosis of liver parenchyma earlier than controls. Analyses of beta-hexosaminidase and lactate dehydrogenase revealed no deviation of enzyme levels either before or after tumor inoculation. The results indicate that a temporary suppression of RE function at the time of tumor inoculation may influence subsequent tumor growth.
Adenocarcinoma↗
The effect of 5-fluoroorotic acid on the early labelling of nucleotides and RNA in whole liver and of RNA in subnuclear fractions in rats given 3H-orotic acid.
Male white rats were given either orotic acid or 5-fluoroorotic acid 60 min, and 3H-orotic acid 3 1/2 min before sacrifice. Liver nucleotides were analyzed by isotachophoresis. The (F)UTP pool increased to the same extent in both groups and showed the same specific labelling. The RNA synthesis, as measured by nmol of UTP entering RNA-UMP/g wet liver tissue was significantly lower in fluoroorotic acid treated rats. In the nucleolar fraction there was an increase in the RNA/DNA ratio, a decrease in the specific RNA labelling and an essentially unaltered specific labelling of RNA/microgram/DNA. The effect on the specific labelling of RNA/microgram DNA was the same in the nucleolar fraction and the nucleolar-free pellet, suggesting that the transcription of RNA in these two fractions proceeded in a similar way. There was a slight increase in the specific RNA labelling of the supernatant subnuclear fraction, containing low-molecular weight RNA. Incorporation into UDP-hexoses and UDP-N-acetylhexosamine was unchanged.
Animals↗
Release of beta-hexosaminidase after administration of different agents affecting the reticuloendothelial system. An experimental study in rats.
Plasma levels of a lysosomal enzyme, beta-hexosaminidase (beta-N-acetylglucosaminidase, EC 3.2.1.30) were studied in Wistar rats after administration of 99mTc -sulfur colloid, 198Au colloid, gelatine (Haemaccel), alcohol, methylpalmitate and zymosan. The activity of beta-hexosaminidase was increased 10, 30 and 60 min after the zymosan injection. After 24 and 48 h, enzyme levels had returned to those at outset. The transient release of beta-hexosaminidase probably occurred only during the phagocytosis of zymosan which was evaluated by histological examination of lung, liver and spleen. After the injection of all other agents tested, no significant aberration of beta-hexosaminidase levels was seen. Activity distribution of the radio-labeled colloids revealed differences in organ uptake which were attributed to a difference in colloid particle size. Although the colloids tested have been used extensively for determination of reticuloendothelial function and histological studies suggest phagocytosis of the particles, their administration did not affect plasma beta-hexosaminidase levels. Since lysosomal enzymes are cleared from the blood predominantly by liver macrophages, the primary location of particle phagocytosis may explain the present findings.
Animals↗
A scintillation camera technique for measurements of the reticuloendothelial function - comparison of different methods for measuring RES function.
A highly standardized 99mTc-sulphur colloid was used to evaluate reticuloendothelial system (RES)-function in the normal rat and after RE blockade by gelatin (Haemaccel). Activity distribution in the animals was measured with a scintillation camera technique. Total uptake of activity in the liver was estimated. From the time-activity curves over the liver, the phagocytic index (kphag) was evaluated. Estimation of the uptake rate of the labelled colloid into the liver and into other parts of the RES was also performed using a two-compartment model. Different methods of evaluation of RE function were compared. It was shown that for a proper estimation of the RE function, the whole uptake curve must be considered. Gelatin (Haemaccel) significantly reduced the total colloid uptake by the liver. The colloid uptake rate into the liver was also significantly reduced. Liver specimens after colloid injection were examined by light and electron microscopy showing vacuolation of hepatocytes and sinusoidal cells probably due to pinocytosis. The technique described enables functional studies of the RES. It has the advantage of noninvasive registrations and is based on the same technical facilities as used for routine liver scintigraphy.
Animals↗
Effect of experimental folate deficiency on lipid metabolism in liver and brain.
1. Rats were given a purified folate-deficient diet containing 5 g succinylsulphathiazole/kg for 4-5 months in two experiments. Control rats were supplemented with folic acid in the drinking-water. 2. Weight gain was much below normal in the folate-deprived rats after the first month. Very low folate levels were recorded in blood, liver and peripheral nerve (12-33% of control). In the central nervous system, including the cerebrospinal fluid, the folate depletion was less conspicuous (50-80% of control). Only marginal signs of anaemia were found and no signs of neurological dysfunction were detected, using nerve conduction velocity measurement and co-ordination tests. 3. Light and electron microscopy of the folate deficient liver revealed fatty infiltration, and enlargement of liver parenchymal cells, nuclei and nucleoli. There was often a considerable amount of bile ductular cells in the lobuli but no cirrhosis. The morphological changes resembled those observed in choline deficiency. 4. Phospholipid N-methylation in liver was depressed in folate-deficiency. This was probably due to a decreased availability of S-adenosylmethionine caused by the low concentrations of methylated folate in liver. Intraperitoneal administration of methionine did not normalize phospholipid methylation. 5. In folate deficiency the proportion of ethanolamine phosphoglyceride in liver was increased at the expense of choline phosphoglyceride, which is consistent with a decreased phospholipid methylation. Also an increase in liver triacylglycerol was noted, in accordance with the morphological observations. Brain lipid composition was unchanged. 6. After the injection of labelled ethanolamine, isotope accumulated in liver phosphoethanolamine in folate deficiency, probably due to an impairment of the CTP:ethanolaminephosphate cytidylyltransferase (EC 2.7.7.14) reaction. The mechanism of this impairment is discussed. 7. Although the low concentrations of folate was the main nutritional change in the deprived animals, changes with respect to vitamin B12 and maybe also choline cannot be excluded. We conclude that some of the changes in folate deficiency, i.e. fatty liver and decreased biosynthesis of liver phospholipids may be due to a precipitated deficiency of lipotropic agents, whereas other differences may be specific for deficiency of folate per se, such as changes in liver phospholipid fatty acids and some of the morphological aberrations.
Animals↗