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Biomedical subjects

J Ericsson

Publications and source records attributed to J Ericsson.

At least 55 records · Page 3Linked to original sources
PubMed1992

Isoprenoid biosynthesis in rat liver peroxisomes. Characterization of cis-prenyltransferase and squalene synthetase.

Isolated peroxisomes were able to utilize [3H]isopentenyl diphosphate to synthesize farnesyl diphosphate, which then was utilized as substrate by both the peroxisomal squalene synthetase and cis-prenyltransferase. The specific activity of squalene synthetase in peroxisomes was as high as in microsomes, i.e. 160 pmol/mg of protein/min. If NADPH was omitted from the assay medium, presqualene diphosphate accumulated, which indicates that the reaction occurs in two steps, as in microsomes. In the presence of NADPH, incorporation from [3H]farnesyl diphosphate was stimulated 3-fold, and the major products were squalene and cholesterol. The specific activity of cis-prenyl-transferase in peroxisomes was 4-fold higher than in microsomes, i.e. 456 pmol of isopentenyl diphosphate incorporated/mg of protein/h. There were two major products formed from farnesyl diphosphate and [3H] isopentenyl diphosphate, i.e. trans,trans,cis-geranylgeranyl diphosphate and long chain polyprenyl diphosphates. The polyprenyl diphosphates had the same chain length distribution as that of dolichol derivatives in rat liver, with the dominating polyisoprenes being C90 and C95. In contrast to the microsomal enzyme, peroxisomal cis-prenyltransferase did not require detergents for optimal activity. The enzyme was associated primarily with the peroxisomal membrane after sonication of the peroxisomes.

Animals↗
PubMed1992

Biosynthesis of trans,trans,trans-geranylgeranyl diphosphate by the cytosolic fraction from rat tissues.

The cytosolic fractions from rat liver, brain, kidney, spleen and testis demonstrate the capacity to synthesize two products from [3H]isopentenyl diphosphate, i.e., farnesyl diphosphate and geranylgeranyl diphosphate. The highest rate of geranylgeranyl diphosphate synthesis was found in brain, testis and spleen, accounting for up to 30% of the total incorporation of radioactivity under optimal conditions. In all tissues examined the geranylgeranyl diphosphate formed was identified as the trans,trans,trans-isomer. The ratio of geranylgeranyl diphosphate to farnesyl diphosphate produced was specific for the tissue investigated and could be altered by the addition of divalent cations. The results in this study demonstrate the presence of a specific trans,trans,trans-geranylgeranyl diphosphate synthetase showing high affinity for farnesyl diphosphate.

Animals↗
PubMed1991

Characterization and distribution of cis-prenyl transferase participating in liver microsomal polyisoprenoid biosynthesis.

The properties of rat liver cis-prenyl transferase, mediating the synthesis of polyisoprenoid pyrophosphate from trans,trans-farnesyl pyrophosphate and [3H]isopentenyl pyrophosphate were studied. The Km values for farnesyl pyrophosphate and isopentenyl pyrophosphate were found to be 25 microM and 4.4 microM, respectively. Appropriate conditions were established to measure the condensation reaction, which was linear during the first hour using 1 mg microsomal protein. Various detergents could solubilize the enzyme, but the presence of Triton X-100 was required during the incubation to obtain full activity. There was also an absolute requirement for Mg2+ and the pH maximum was 7.0. Inorganic phosphate, especially pyrophosphate, proved to be inhibitory. cis-Prenyl transferase is associated mainly with the cytoplasmic surface of rough microsomes and, to some extent, also with smooth I microsomes, but was almost absent from smooth II microsomes. At all localizations, the product is polyprenyl pyrophosphate and to some extent, also polyprenyl monophosphate. The isoprenoids formed contain 15-18 units in the presence of detergents and 16-20 units in the absence of detergents.

Animals↗
PubMed1991

Involvement of sterol carrier protein-2 in dolichol biosynthesis.

The effect of sterol carrier protein-2 (SCP-2) on dolichol biosynthesis by rat liver microsomes was investigated. cis-Prenyltransferase activity was stimulated 7-fold in the presence of 5 micrograms of purified SCP-2/mg of microsomal protein, which was similar to the increase obtained by adding detergent. The polyisoprenoid pattern obtained in the presence of SCP-2 was the same as that present in rat liver, in contrast to the pattern appearing upon incubation of microsomes with detergent, which gave shorter polyisoprenoids. Like SCP-2, the cytosolic fraction from rat liver also stimulated cis-prenyltransferase. Incubation with cytosol pretreated with anti-SCP-2 showed no stimulatory effect and led to the accumulation of shorter polyisoprenoids. SCP-2 had no appreciable effect on polyprenol alpha-saturase, dolichol kinase, dolichyl phosphate phosphatase, or acyl-CoA:dolichol acyltransferase. The results demonstrate that SCP-2 greatly stimulates and may regulate the condensation reactions mediated by cis-prenyltransferase in the process of dolichol biosynthesis and permits polymerization of the polyisoprenoid to its natural chain length.

Albumins↗
PubMed1990

Metabolism of fatty acids and their incorporation into phospholipids of the mitochondria and endoplasmic reticulum in isolated hepatocytes determined by isolation of fluorescence derivatives.

Isolated hepatocytes were incubated in the presence of [14C]palmitic, [14C]linoleic or [14C]linolenic acid and the time-courses of incorporation of radioactivity into phosphatidylcholine and phosphatidylethanolamine of microsomes and mitochondria were followed. For this purpose a procedure was developed for HPLC separation of 9-diazomethylanthracene (ADAM) derivatives of fatty acids. When [14C]palmitic acid was used, the major product of elongation and desaturation was octadecadienoic acid, which accounted for 35-65% of the total radioactivity. Labeled palmitoleic, stearic and oleic acids could also be isolated. In fatty acids which do not participate to any large extent in deacylation-reacylation reactions, the pattern of incorporation was characteristic: a high rate of incorporation into microsomal and a low rate of incorporation into mitochondrial phospholipids during the first 40 min, followed by a decrease in the former and an increase in mitochondrial labeling. This pattern is consistent with the fact that de novo synthesis of these two phospholipids occurs in the endoplasmic reticulum in vivo. When cells were incubated in the presence of [14C]linoleic acid, 70-90% of the radioactivity recovered in phospholipids was in this same form, whereas the remaining label was mainly in arachidonic acid and, to some extent, in eicosatrienoic acid. When hepatocytes were incubated in the presence of [14C]linolenic acid, 70-85% of the radioactivity in isolated phospholipids was associated with linolenic acid. As much as 20% of the label was recovered in docosahexanoic acid and 5-10% in arachidonic acid. In the case of the two latter labeled substrates the exchange reactions seem to dominate over de novo synthesis. For phospholipids synthesized de novo the transfer from the endoplasmic reticulum to mitochondria requires about 3 h.

Animals↗
PubMed1989

Origin and relationship between different cell types in malignant fibrous histiocytoma.

The derivation of histiocyte-like cells in malignant fibrous histiocytoma (MFH) has been a matter of debate. To shed light on this problem two cell lines from two subsequent recurrencies of MFH were established. The existence of two different cell populations, mainly fibroblast-like in the first cell line and mainly histiocyte-like in the second, was shown by light and electron microscopy, DNA measurements, and karyotype analysis. By detailed banding analysis and identification of several identical chromosomal marker types in the two cell lines, it was proven that they originally derived from the same single cell or single clone. Because the first cell line, with mainly fibroblast-like cells, was in the hypotriploid region and the second, with mainly histiocyte-like cells, was in the penta-hexaploid region, the data explained the appearance of histiocyte-like cells in MFH as a consequence of chromosomal progression.

Aged↗
PubMed1988

Cytidine 5'-triphosphate-dependent dolichol kinase and dolichol phosphatase activities and levels of dolichyl phosphate in microsomal fractions from highly differentiated human hepatomas.

Homogenates and microsomal fractions prepared from biopsies of highly differentiated human hepatocellular carcinomas were found to contain low levels of dolichol in comparison with control tissue. In contrast, the amount of dolichyl phosphate in tumor homogenates was unchanged and actually increased in the microsomal fraction. The pattern of individual polyisoprenoids, both in the free and the phosphorylated dolichol fractions of hepatomas, did not exhibit any major alterations compared to the control. The rates of incorporation of [3H]mevalonic acid into dolichol and dolichyl phosphate in hepatomas were low. The dolichol monophosphatase activities in microsomal fractions from hepatomas and controls did not show any major differences, whereas the activity of the CTP-dependent dolichol kinase was increased in tumor microsomes. Glycosylation of endogenous dolichyl phosphate and of total protein using certain nucleotide-activated sugars was found to be slightly elevated in microsomal fractions from the tumor itself when compared to the control. The reasons for the differences in the levels of polyisoprenoids in hepatomas and control tissue are discussed.

Carcinoma, Hepatocellular↗
PubMed1988

Pleural mesotheliomas and asbestos exposure in the pulp and paper industries: a new risk group identified by linkage of official registers.

Analysis of data obtained by linking the 1960 Swedish Census and the Swedish Cancer Registry has demonstrated an increased risk of pleural mesothelioma among pulp and paper workers. The present study was undertaken with the aim of revealing possible environmental risk factors. The work histories of the 25 cases identified earlier were reviewed. "Certain" or "probable" exposure to asbestos was found among 70% of these workers. The study illustrates how linkage of official registers can be used to identify new risk environments and encourage the establishment of preventive measures.

Asbestos↗
PubMed1988

Lung function in workers exposed to soft paper dust.

In a cross-sectional study, 13 nonsmoking men with heavy exposure to paper dust were compared with 14 unexposed men, mainly office workers, employed at the same paper mill. They were studied using questionnaires, physical examinations, pulmonary function studies, and chest radiographs. Among those exposed there was an increased lung elastic recoil pressure (Pel) compared with controls which was significant (p less than 0.05) at the maximal level of total lung capacity (100% TLC). Furthermore, among the exposed workers there was also a significantly (p less than 0.05) decreased residual volume (RV). Two of the exposed men underwent lung biopsies, one of which showed fibrotic alveolar walls. Among the exposed there was also a significant (p less than 0.05) predominance of symptoms from the lower respiratory tract. We suggest that the observed pulmonary function impairment taken together with the histological examination of the lung biopsies are signs of a nonspecific reaction to high levels of paper dust.

Adult↗
PubMed1988

Morphological studies on endocytosis of chondroitin sulphate proteoglycan by rat liver endothelial cells.

Endocytosis via the hyaluronic acid/chondroitin sulphate receptor of rat liver endothelial cells was studied ultrastructurally, by use of a probe consisting of chondroitin sulphate proteoglycan attached to 15-nm gold particles. The probe bound to the surface of the cells exclusively in coated regions of the plasma membrane. Internalization at 37 degrees C took place in less than one minute during which time interval the bound probe was transferred to coated vesicles. Further transfer to lysosomes was delayed in association with an accumulation of probes in a prelysosomal compartment consisting of large vacuoles in which probes lined the inner aspect of the membrane. Transport to lysosomes occurred only after a lag phase of at least 40-60 min at 37 degrees C.

Animals↗
PubMed1988

Respiratory symptoms and lung function following exposure in workers exposed to soft paper tissue dust.

The objective of this study was to investigate if the dust in a mill producing soft paper tissue caused respiratory symptoms or impaired respiratory function. Using a questionnaire and spirometry, 355 persons were examined. They were divided into three groups according to present exposure to dust; low (less than 1 mg/m3), moderate (1-5 mg/m3) and heavy (greater than 5 mg/m3). There was a dose-dependent increase of symptoms from the upper respiratory tract. However, coughing and coughing with phlegm were not found to be more common among persons with heavy exposure compared to those with low exposure to the dust. There was no difference in FEV1 or FVC during a work shift. Persons with long-term (greater than 10 years) and heavy exposure to dust seemed to have impaired respiratory function compared to those with low and/or short-term exposure to the dust.

Adult↗
PubMed1987

Separation and quantitation of dolichyl esters by high-performance liquid chromatography.

An HPLC procedure for the isolation and quantitation of total and individual dolichyl esters in tissues has been developed. The purified lipid extracts are subjected to sequential reversed-phase, straight-phase, and reversed-phase HPLC, which yield complete resolution and high recovery of the individual dolichyl esters. The isoprenoid distribution in the esterified fraction was similar to that of the free alcohol fraction in liver, kidney, and spleen. All fatty acids present in the total fraction were also recovered in all the individual polyisoprenoids. Dolichyl esters thus appear to differ from other lipid esters in tissues in containing a broader range of fatty acids.

Animals↗
PubMed1987

Changes in hepatic dolichol and dolichyl monophosphate caused by treatment of rats with inducers of the endoplasmic reticulum and peroxisomes and during ontogeny.

Rats were treated with various inducers of the endoplasmic reticulum and peroxisomes and the properties and distributions of dolichol and dolichyl phosphate analyzed. The treatment of rats with carcinogenic agents 2-acetylaminofluorene, N-nitrosodiethylamine and 3-methylcholanthrene and with the compounds such as phenobarbital, terpentine, cholestyramine and di(2-ethylhexyl)phthalate have all caused changes in the microsomal or lysosomal contents of dolichol to various extents, but only the latter group influenced dolichyl-P concentration. Shortly after birth, the hepatic content of dolichyl-P reaches the adult level, whereas the level of the free alcohol is low at birth but increases continuously thereafter. Incorporation of [3H]mevalonate into dolichol was also dependent on factors other than de novo synthesis, e.g., the pool size. Rates of glycosylation reactions dependent on dolichyl-P exhibit considerable changes but are independent of the existing levels of lipid intermediate. GDP-mannosyl transferase activity increases greatly with birth, but the enzyme activity returns to the adult level within a day after birth. These results demonstrate that structural and functional modifications induced with drugs can greatly influence the content and distribution of dolichol which are independent of the existing levels of dolichyl-P.

2-Acetylaminofluorene↗
PubMed1987

Geographic differences in the prevalence and distribution of large-bowel polyps--colonoscopic findings.

The large-bowel polyp pattern in two widely separated geographic regions of Sweden, Bollnäs in the central part and Trelleborg in the south, was studied prospectively by colonoscopic polypectomy. In Bollnäs 11.8% of 1,153 patients had neoplastic, and 3.8% hyperplastic, polyps. In Trelleborg 29% of 1,040 patients had neoplastic, and 17.3% hyperplastic, polyps. Furthermore, the Trelleborg patients had, on average, more polyps per patients than their Bollnäs counterparts: 2.0 versus 1.5 neoplastic, and 2.1 versus 1.7 hyperplastic, polyps. There was a marked difference in the anatomic location of the polyps between the two regions: in Trelleborg 55.4% of the neoplastic, and 40.5% of the hyperplastic polyps were distributed above the rectosigmoid, compared with 20.9% and 26.4%, respectively, in Bollnäs. The findings offer an explanation of the fact that the incidence of colorectal carcinoma in the Malmö region, close to the Trelleborg area, is the highest in Sweden.

Adult↗