Showing papers on "Liver cell published in 1970"
TL;DR: An overload of the liver cell with numerous lipid- soluble drugs increases drug metabolizing enzymes in the endoplasmic reticulum and augments the smooth membranes in the hepatocytes with the results that all lipid-soluble compounds reacting with cytochrome-P450 are oxidized more rapidly.
211 citations
TL;DR: The main topics are: Effect of oral contraceptives on the liver, the mechanism of the cholestatic effect of steroids, possible genetical defects involved and the likely connection between the metabolism of hormonal steroids and the formation of gallstones in women.
185 citations
TL;DR: The study confirmed the existence of a distinct correlation beween the histologic type of the tumor, its gross appearance, and the clinical course of the disease, as compared with other types of hepatoblastoma.
Abstract: Clinical data and morphological materials from 70 cases of liver-cell carcinoma in infants and children in Japan were collected and studied. The cases were classified into 4 types according to the histopathologic appearance of the epithelial components: 1. adult type; 2. anaplastic type; 3. embryonal type; and 4. fetal type. The study confirmed the existence of a distinct correlation beween the histologic type of the tumor, its gross appearance, and the clinical course of the disease. Twenty-seven of the 70 cases underwent radical surgery. Postoperative prognosis was studied in these cases according to histologic types of tumor. Of 9 long-term survivors (i.e., surviving more than 2 years), 7 were found to belong to the fetal type. No difference was found in prognosis between the cases with and without osteoid tissue in tumor. The benign character of the fetal type, as compared with other types of hepatoblastoma, was demonstrated even in infants under 12 months of age.
150 citations
TL;DR: Delta-Aminolevulinic acid synthetase is induced in chick embryo liver culture by the natural steroid, etiocholanolone, and by the foreign chemical, 3,5-dicarbethoxy-1,4-dihydrocollidine at the level of transcription.
Abstract: delta-Aminolevulinic acid synthetase is induced in chick embryo liver culture by the natural steroid, etiocholanolone, and by the foreign chemical, 3,5-dicarbethoxy-1,4-dihydrocollidine at the level of transcription. Alternatively, inducing chemicals such as allylisopropylacetamide and gamma-hexachloro-cyclohexane act primarily at the level of translation. Hemin (K(i) = 5 muM) inhibits the induction at the level of translation. In liver cell culture, the half-life of delta-aminolevulinic acid synthetase is 3 hr, that of mRNA about 5 hr.
128 citations
TL;DR: It is concluded that albumin is synthesized on bound ribosomes, subsequently is transferred to the cavities of rough-surfaced endoplasmic reticulum, and then undergoes migration to the smooth-surface endoplasmsic retICulum and the Golgi apparatus.
Abstract: A comparative biochemical and radioautographic in vivo study was performed to identify the site of synthesis and route of migration of albumin in the parenchymal liver cell after labeling with leucine-14C or leucine-3H via the portal vein. Free cytoplasmic ribosomes, membrane-bound ribosomes, rough- and smooth-surfaced microsomes, and Golgi membranes were isolated. The purity of the Golgi fraction was examined morphologically and biochemically. After administration of leucine-14C, labeled albumin was extracted, and the sequence of transport was followed from one fraction to the other. Approximately 2 min after the intravenous injection, bound ribosomes displayed a maximal rate of leucine-14C incorporation into albumin. 4 min later, a peak was reached for rough microsomes. Corresponding maximal activities for smooth microsomes were recorded at 15 min, and for the Golgi apparatus at ∼20 min. The relative amount of albumin, calculated on a membrane protein basis, was higher in the Golgi fraction than in the microsomes. By radioautography the silver grains were preferentially localized over the rough-surfaced endoplasmic reticulum at the 5 min interval. Apparent activity in the Golgi zone was noted 9 min after the injection; at 15 and 20 min, the majority of the grains were found in this location. Many of the grains associated with the Golgi apparatus were located over Golgi vacuoles containing 300–800 A electron-opaque bodies. It is concluded that albumin is synthesized on bound ribosomes, subsequently is transferred to the cavities of rough-surfaced endoplasmic reticulum, and then undergoes migration to the smooth-surfaced endoplasmic reticulum and the Golgi apparatus. In the latter organelle, albumin can be expected to be segregated together with very low density lipoprotein in vacuoles known to move toward the sinusoidal portion of the cell and release their content to the blood.
116 citations
95 citations
TL;DR: It was shown that peroxisomes are destroyed in a completely random way, probably as wholes since the apparent half-life was the same for all subfractions, about 3½ days.
Abstract: Rat liver peroxisomes have been separated according to size by zonal sedimentation. A method is described for calculating the size of the particles from their final position in the gradient. Peroxisomes seem biochemically homogeneous throughout their size distribution. 3 hr after injection of tritiated leucine, the specific radioactivity of catalase is the same in peroxisomes of different sizes, and it remains so for up to 1 wk after administration of the precursor. This observation rules out the possibility that peroxisomes have an extended period of independent growth. If individual particles maintain an independent existence, they must be formed very rapidly. The other possible explanation is that peroxisomes exchange material within the liver cell.
85 citations
TL;DR: Autoradiographic and biochemical studies were performed to elucidate the restitution of rat liver after galactosamine hepatitis and the normalization of serum enzyme levels and of the liver glycogen store was paralleled to the histologic signs of regeneration.
79 citations
TL;DR: The results indicate that the ratio between 3-sulphates of 17β-hydroxysteroids and the corresponding 17-ketosteroids in plasma is determined by the NADH/NAD+ ratio in the liver cell cytoplasm.
Abstract: Ethanol intake has been shown to cause a rapid increase of the concentration of androst-5-ene-3β,17β-diol 3-sulphate and a simultaneous decrease of the concentration of dehydroepiandrosterone sulphate in plasma. The ratio between the 17β-hydroxysteroid and the 17-ketosteroid increased with the ethanol concentration up to 30–50 mg ethanol/100 ml blood when a 6 to 10-fold increase was obtained. The ratios between the 3-sulphates of 5α-androstane-3α, 17β-diol and androsterone and between the monosulphates of 5α-androstane-3β,17β-diol and 3β-hydroxy-5α-androstan-17-one also increased during ethanol metabolism. Deuterium was rapidly incorporated into the D-ring of the three C19 steroid diols, reaching about 20 atom per cent excess 10 to 20 min after oral administration of 0.1 g [1-2H2]ethanol per kg body weight. The concentrations of steroids with a sulphate group at C-17 did not change and deuterium was not incorporated into these steroids or into the 17-ketosteroid sulphates. The ratio between the 3-sulphates of 5-pregnene-3β,20α-diol and pregnenolone increased only slightly and incorporation of deuterium into the side chain of the C21 diol reached a maximum of about 4 atom per cent excess about 1 hour after the ethanol administration.
The results indicate that the ratio between 3-sulphates of 17β-hydroxysteroids and the corresponding 17-ketosteroids in plasma is determined by the NADH/NAD+ ratio in the liver cell cytoplasm. They also indicate that the 3-sulphate of 5-pregnene-3β,20α-diol is not formed from pregnenolone sulphate at the same site or with the use of the same coenzyme molecules as the 17β-hydroxysteroids.
55 citations
Journal Article•
TL;DR: Treatment of 100-g male Fischer rats with an i.p. dose of 1 mg/kg of aflatoxin B1 causes a rapid and marked inhibition of the activity of liver DNA-dependent RNA polymerase, and a decrease in nuclear RNA/DNA ratio is observed under conditions whereRNA polymerase activity is decreased.
Abstract: Summary Treatment of 100-g male Fischer rats with an i.p. dose of 1 mg/kg of aflatoxin B1 causes a rapid and marked inhibition of the activity of liver DNA-dependent RNA polymerase. Over a period of 36 hr after dosing, ultrastructural alterations of the liver cell nucleolus generally correlate with the inhibition of enzyme activity. Mg++-activated and Mn++-(NH4)2SO4-activated RNA polymerase activities, 15 min after dosing, are maximally inhibited by about 60%; this inhibition continues to 12 hr. By 36 hr, enzyme activities have returned to pretreatment levels. Hepatocyte nucleoli 15 min after treatment show decreased prominence of nucleolonema, and nucleolar microsegregation is observed. Macrosegregation of granular and fibrillar nucleolar components (nucleolar capping) is demonstrated within 1 hr after treatment, and the segregation persists up to 12 hr. By 36 hr, reintegration of nucleolar components is observed. Inhibition of RNA polymerase activity is directly related to aflatoxin B1 dose, with a correlation coefficient of -0.89 for the Mg++-activated system and -0.97 for the Mn++-(NH4)2SO4-activated system. Nucleolar disorganization is observable at 0.2 mg/kg aflatoxin B1 but is not demonstrable at 0.1 mg/kg, a dose which is capable of a 5% inhibition of both types of enzyme activity. A decrease in nuclear RNA/DNA ratio is observed under conditions where RNA polymerase activity is decreased.
Journal Article•
TL;DR: The cytochrome contents in ascites hepatomas and some other fast-growing tumor cells of rats and mice were determined spectrophotometrically at room and low temperature and compared with those in normal liver cells, indicating that these cytochromes are not linked to the electron transport chain.
Abstract: Summary The cytochrome contents in ascites hepatomas and some other fast-growing tumor cells of rats and mice were determined spectrophotometrically at room and low temperature and compared with those in normal liver cells. On a protein basis, the contents of cytochromes a(+ a3), b, and c1 in the various hepatomas are rather constant, and the levels are about one-half or one-third of those in normal livers. However, the content of cytochrome c is nearly equal to that in normal livers, and a high c/a(+ a3) ratio has been observed in tumor cells. On a cell basis, the cytochrome concentrations in a tumor cell are much lower than those in a normal liver cell. In tumor cells, a considerable amount of cytochrome b [and a part of cytochromes c and a(+ a3)] could not be reduced immediately after anaerobiosis or by cyanide or sulfide treatment, indicating that these cytochromes are not linked to the electron transport chain. In normal liver cells all of the cytochromes, a(+ a3), b, c, and c1, are linked directly to the electron transport chain. No cytochrome b5 or P-450 was detected in the hepatomas and other tumor cells used, while hemoproteins 559 and 565 were present in these cells and their contents were nearly equal to those in normal livers.
TL;DR: It is considered very likely that the invariable presence of hepatic siderosis in symptomatic porphyria is more than incidental and that the presence of excessive iron in the liver cells is an important factor determining the development of symptomatic porphryia.
Abstract: Summary. The combination of iron overload and hexachlorobenzene (HCB) feeding in rats produces an ‘experimental symptomatic porphyria’. Studies of hepatic haem biosynthesis in this model showed a decrease in total liver haem and cytochromes P450 and b5, together with decreased incorporation of 14C-succinate into liver haem and an absence of uroporphyrinogen decarboxylase activity. A marked alteration was found in the redox state of the liver cell cytoplasm both in siderotic and non-siderotic animals after HCB feeding; the ratio NAD: NADH was increased more than two-fold. These findings suggest that the primary effect of HCB with regard to liver haem biosynthesis may be this change in the redox state, possibly leading to decreased ability to maintain porphyrinogens in the reduced form and that the additional effect of iron overload is mediated by impairment of uroporphyrinogen decarboxylase activity and an increased rate of degradation of microsomal drug detoxifying cytochromes. It is probable that in human symptomatic porphyria a number of factors are similarly responsible for the excessive production and excretion of porphyrins.
TL;DR: It is concluded that the appreciable turnover of mitochondrial phosphatidylcholine observed in vivo can be explained most satisfactorily by assuming a transfer of newly synthesized phospholipid molecules from the endoplasmic reticulum.
Abstract: The incorporation of [Me-14C]choline into the phosphatidylcholine of subcellular fractions of rat liver has been examined. The mitochondrial fraction shows a minimal phosphatidylcholine synthesis compared with that produced by adding microsomes providing an incubation medium which allows adequate phospholipid synthesis is used. The small mitochondrial incorporation can be partly if not wholly explained by microsomal contamination or a non-energy dependent exchange process. It is concluded that the appreciable turnover of mitochondrial phosphatidylcholine observed in vivo can be explained most satisfactorily by assuming a transfer of newly synthesized phospholipid molecules from the endoplasmic reticulum.
Journal Article•
TL;DR: The marmoset, Saguinus mystax, developed signs of disease similar to human hepatitis when inoculated with marmosett sera containing Deinhardt's hepatitis agent, or sera from patients with infectious hepatitis but not when inoculation with serum containing hepatitis-associated antigen or with partially purified antigen.
Abstract: SummaryThe marmoset, Saguinus mystax, developed signs of disease similar to human hepatitis when inoculated with marmoset sera containing Deinhardt's hepatitis agent, or sera from patients with infectious hepatitis but not when inoculated with serum containing hepatitis-associated antigen or with partially purified antigen. The evidence of disease were 3- to 10-fold increase above normal SGPT levels and histologic changes of single liver cell necroses with periportal lymphocytic infiltration. Hepatitis-associated antigen was not found in any marmoset sera by complement-fixation tests or electron microscopy.
TL;DR: The data suggest that the epinephrine action on glucokinase induction may result both from a direct effect on the liver cell, possibly mediated by cyclic AMP, and a blockade of insulin secretion at the pancreas.
TL;DR: There is linear relationship between the K(+) content of the slices and the transport of protein, which is probably important in ethionine and carbon tetrachloride poisoning in the rat, and may be significant in liver transplantation.
Abstract: 1. The incorporation of l-[1-14C]leucine into the proteins of liver slices and into the serum albumin and lipoproteins transported by these slices was investigated. 2. Transport rates were found to be dependent on the K+ content of the slices. 3. The effect of K+ on transport of serum albumin and of serum lipoprotein can be separated from any effect on synthesis by altering K+ concentrations after inhibition of protein synthesis by cycloheximide or puromycin. 4. The effect of low K+ concentrations is reversible. 5. There is linear relationship between the K+ content of the slices and the transport of protein. A simple method is described for maintaining various steady concentrations of K+ in the liver slices. 6. K+ may be replaced by Rb+. Cs+ is partly effective, but NH4+ and Li+ are no more effective than Na+. 7. We found evidence that K+ content rather than the flux rates of K+ or Na+ is important in this effect. 8. These results are probably important in ethionine and carbon tetrachloride poisoning in the rat, and may be significant in liver transplantation.
TL;DR: Analysis of associated biochemical features suggested a relationship to physical biliary obstruction rather than a derangement of liver cell function, and lipoprotein X was found in 45% of cases of liver disease with cholestatic features, and was not detected in cases of Liver disease without cholESTasis.
Abstract: An abnormal lipoprotein, containing a high proportion of unesterified cholesterol and phospholipid, has previously been described as occurring in the serum of patients with obstructive jaundice, and has been called lipoprotein X. Using an immunoelectrophoretic method for the detection of lipoprotein X in serum, the sera of 97 patients with liver disease have been screened and the associated biochemical features measured.Lipoprotein X was found in 45% of cases of liver disease with cholestatic features, and was not detected in cases of liver disease without cholestasis. The incidence of lipoprotein X in different causes of cholestatis varied, and while it was commonest in cases of extrahepatic obstruction of recent onset, occurring in 75% of cases, it was also found in primary biliary cirrhosis in 48% of cases, and in cholestatic hepatitis, less commonly.The cause of the appearance of lipoprotein X is unknown, but analysis of associated biochemical features suggested a relationship to physical biliary obstruction rather than a derangement of liver cell function.
TL;DR: It appears that the homologue synthesized is controlled by isoprenyl pyrophosphate available for condensation.
TL;DR: Mitochondrial abnormalities provided the best indication of the development of coagulative necrosis, but the findings cast doubt on the importance of calcium accumulation within mitochondria as a causative factor in the initiation of necrosis.
TL;DR: There is evidence that toxic effects in the livers and sometimes the lungs of experimental animals are caused by metabolites formed by enzymic dehydrogenation of the alkaloids in the liver, which are highly reactive dihydropyrrolizine esters which can react with nucleophilic tissue constituents.
Abstract: MANY pyrrolizidine alkaloids have toxic effects in the livers and sometimes the lungs of experimental animals1, and there is evidence that these effects are caused by metabolites formed by enzymic dehydrogenation of the alkaloids in the liver2–4. These metabolites are highly reactive dihydropyrrolizine esters which when released in the liver cell can react with nucleophilic tissue constituents. The heterocyclic moiety can become bound to the tissue while the acid moiety is liberated as the anion.
TL;DR: Sera from normal persons and patients with acute viral hepatitis were mixed with indocyanine green (ICG), then fractionated on Sephadex G-200 columns, finding changes in the ICG curves may result from interaction between serum proteins and liver cell proteins originating from damaged liver cells, an interaction leading to the formation of complexes of high molecular weight.
Abstract: Sera from normal persons and patients with acute viral hepatitis were mixed with indocyanine green (ICG), then fractionated on Sephadex G-200 columns. Alternate portions of the effluent were examined spectrophotometrically at 280 nm (for protein content) and at 800 nm (for ICG concentration). In most normal sera, three distinct ICG peaks were distinguished, the first and third corresponding exactly to the position of protein peaks, the second being most frequently shifted slightly toward heavier protein fractions. By graphic analysis, up to three additional masked peaks were usually detected in ICG curves. The individual fractions on ICG curves were numbered from I to VI, beginning with the fraction of greatest molecular weight. In the acute phase of viral hepatitis, the ICG curve was characteristically changed: fraction IV decreased significantly or even disappeared, and fraction I simultaneously increased. Fractions III and V also increased, but less. These changes in the ICG curves may result from interaction between serum proteins and liver cell proteins originating from damaged liver cells, an interaction leading to the formation of complexes of high molecular weight.
TL;DR: A correlation was found between the different types of cholestasis, the level of bilirubinaemia, and its dynamic evolution, which suggests that the proposed types of dilation may represent successive stages of increasing cholESTasis.
Abstract: A histochemical study of conjugated and total bilirubin was made on liver biopsies of 150 patients. Three types of cholestasis were defined: type I, characterized by the presence of intracellular pigment granules in the hepatocytes; type II, showing intracellular granules and extracellular thrombi (this group may be subdivided according to the eventual presence of coarse pigment deposits in the parenchymal cells); and type III, showing intracellular granules, extracellular thrombi, and also bile pigment in the Kupffer cells. The fine liver cell granules correspond mainly to conjugated bilirubin, whereas the coarse deposits usually contain unconjugated pigment. The extracellular thrombi mostly contain conjugated bilirubin; the Kupffer cell pigment is predominantly of the unconjugated type. In cholestasis types II and III a diffuse directly reacting pigment is also observed. The finding of unconjugated pigment in different locations and the eventual deconjugation by β-glucuronidase is discussed. A correlation was found between the different types of cholestasis, the level of bilirubinaemia, and its dynamic evolution. This suggests that the proposed types of cholestasis may represent successive stages of increasing cholestasis. The type of cholestasis and the nature of the pigment are largely independent of the aetiology. It is shown that a large percentage of minor degrees of cholestasis is missed when only conventional histological methods are used. The mechanisms by which morphological cholestasis is brought about are discussed in the light of the present findings.
TL;DR: The survival of four species of amphibians (Desmognathus fuscus, Taricha granulosa, Amphiuma means, and Necturus maculosus) was followed after acute x irradiation to determine survival parameters.
Abstract: The survival of four species of amphibians (Desmognathus fuscus, Taricha granulosa, Amphiuma means, and Necturus maculosus) was followed after acute x irradiation. Survival parameters were determined from the literature for three additional species (Rana pipiens, Notophthalmus viridescens, and Ambystoma mexicanum). Nuclear volumes (NV) and interphase chromosome volumes (ICV) were determined from measurements of fixed and sectioned liver cell nuclei. An exposure of 1000 R was 100% lethal for Desmognathus, Taricha, Amphiuma, and Necturus, and 94% lethal for Rana. However, when the latent periods, preceding the time when mortalities increase sharply, were compared by species, it was found that they increased with increased nuclear and/or chromosome volumes. Median survival times after 1000 R also increased with increasing nuclear and/or chromosome volumes. The ${\rm LD}_{50/30}$ values for Rana, Desmognathus, and Notophthalmus, plotted against ICV, suggest that species with larger chromosomes are progressive...
TL;DR: The results are interpreted to mean that the appearance of 3 H-HGH in the particulate fractions at these early time periods may have functional significance, and that important initial binding sites of growth hormone in the liver cell may be mitochondria and microsomes.
TL;DR: Findings from the first report on the effects of various laboratory procedures on the virulence for pigeons of the Jones' Barn (JB) strain of Trichomonas gallinae (Rivolta) suggested undertaking additional investigations of the ways whereby different laboratory procedures might affect thevirulence of the JB strain.
Abstract: With dimethyl sulfoxide as the cryoprotectant, axenic cultures of three isolates (JBIV, JBV, JBVI) of the Jones' Barn (JB) Trichomonas gallinae strain retained their original virulence for pigeons after 5, 5.5, and 7 years of storage at subzero temperatures, primarily in liquid nitrogen at -196 C. The closely comparable times required by noncloned and cloned populations of the JBVI trichomonads to kill Trichomonas-free, nonimmune pigeons indicated the homogeneity of the JB strain with respect to virulence. Although higher pathogenicity for birds was retained by the JBVI parasites maintained for 1 year by serial intraperitoneal passages in mice than by those kept for the same length of time in nonliving media, it was much lower than the virulence typical of the JB strain. The flagellates transferred in mice did not kill the avian hosts and their original pathogenicity levels could not be restored by several bird-to-bird passages. Nearly full virulence for pigeons was retained by the JBVI isolate which had been maintained for up to 1 year in the presence of chick liver cell cultures. Cell culture medium-CPLM mixture had no virulence-preserving effect. JBV trichomonads kept for 22.5 weeks in a CPLM-type medium, which contained no added carbohydrates and in which little division of the parasites took place, appeared to retain their pathogenicity for birds for a longer time than when maintained in the conventional CPLM and fluid thioglycollate media. The first report on the effects of various laboratory procedures on the virulence for pigeons of the Jones' Barn (JB) strain of Trichomonas gallinae (Rivolta) summarized the experimental results obtained during the early stages of our study (Stabler et al., 1964). According to these results: (1) prolonged (19 to 21 weeks) axenic cultivation of the JB parasites by serial transfers in nonliving media at 37 + 0.5 C caused pathogenicity loss; (2) trichReceived for publication 12 March 1970. * This investigation was supported by Research Grant AI00742, from the NIAID, U. S. Public Health Service. t Department of Biology, Colorado College, Colorado Springs, Colorado 80903. t Permanent address: Department of Protozoology, Institute of Parasitology, Czechoslovak Academy of Sciences, Prague, Czechoslovakia. Dr. Kulda spent 2 years as Research Associate in the Department of Zoology, University of Massachusetts at Amherst. During this period he was supported mainly by Research Grants AI00742-13, 14, from NIAID; part of his support was provided by Biomedical Sciences Support Grant 5-SO5-FR07083-03, U. S. Public Health Service. ? The help of Mrs. Mary Tarr Hadley in certain parts of this investigation is hereby acknowledged. omonads stored at -20 or -72 C for 52 weeks retained their original virulence level; (3) pathogenicity loss was enhanced by the inclusion of penicillin and streptomycin in the original isolation medium (the JB flagellates ceased to kill nonimmune pigeons after 9 weeks of cultivation at 37 ? 0.3 C). These findings, which served as the basis for subsequent immunologic (Goldman and Honigberg, 1968; Honigberg and Goldman, 1968; Stepkowski and Honigberg, in Honigberg, 1969) and biochemical (Honigberg and Livingston, 1968) studies, suggested undertaking additional investigations of the ways whereby different laboratory procedures might affect the virulence of the JB strain. The present paper deals with the results obtained in the course of these investiga-
TL;DR: It appears that for tumour development a proliferative response must occur in the presence of carcinogen.