Biomedical subjects

C Andersson

Publications and source records attributed to C Andersson.

At least 73 records · Page 4Linked to original sources

PubMed1997

Screening for the presence of polyglycosylceramides in various tissues: partial characterization of blood group-active complex glycosphingolipids of rabbit and dog small intestines.

Twenty different human and animal tissues were investigated for the presence of polyglycosylceramides. The glycolipids were isolated by peracetylation of dry tissue residues left after conventional lipid extraction, followed by extraction with chloroform and subsequent Sephadex LH-20, Sephadex LH-60 and silica gel chromatography. In most of the cases only trace amounts of complex glycolipids were found. Distinct bands of glycosphingolipids migrating on TLC plates in a region of brain gangliosides and below were observed in bovine erythrocytes, human leukocytes and human colon mucosa. Definite fractions of polyglycosylceramides were isolated from rabbit small intestine, dog small intestine, human placenta and human leukocytes. The polyglycosylceramides of dog and rabbit intestine were characterized by colorimetric analysis, methylation analysis, mass spectrometry and immunological assays. The dog material contained branched carbohydrate chains with repeated fucosylated N-acetyllactosamine units. Rabbit intestine polyglycosylceramides resembled rabbit erythrocyte polyglycosylceramides with Hex-Hex- terminal determinants but were more complex in respect of sugar composition and structure. The material isolated from dog intestine showed A, H, Le(x) and Le(y) blood group activities. Polyglycosylceramides of human erythrocytes, placenta and leukocytes showed strong binding affinity for Helicobacter pylori, while polyglycosylceramide fractions from rabbit and dog intestine were receptor-inactive for this bacterium or displayed only weak and poorly reproducible binding.

ABO Blood-Group System↗

PubMed1997

Oxygen cost, walking speed, and perceived exertion in children with cerebral palsy when walking with anterior and posterior walkers.

Walkers with the frame positioned behind the child have been advocated recently, mainly because they may allow a more upright and therefore more normal ambulation and perhaps encourage favourable neuromuscular development. The purpose of this study was to estimate and compare speed, energy cost, and perceived exertion during walking with an anterior walker and a posterior walker. Ten children with spastic diplegia, average age 11 years, who were familiar with both types of walker participated in the study. Spasticity was measured according to the modified Ashworth scale. Oxygen cost was determined by the argon-diluted method using a mixing box mounted on a backpack, and the perceived exertion was graded. The results of the study showed that there are no differences in the measured variables in walking between the anterior and the posterior walker in children familiar with both walkers and also that most of the children preferred the posterior walker.

Adolescent↗

PubMed1997

Formulation of enamel matrix derivative for surface coating. Kinetics and cell colonization.

Enamel Matrix Derivative (EMD) contains a protein complex belonging to the amelogenin family. Enamel matrix as well as EMD have been found to promote periodontal regeneration when applied onto denuded root surfaces in dehiscence models. In the present studies it is shown that propylene glycol alginate (PGA) is a suitable vehicle for EMD for its local application. EMD can be dissolved in PGA at an acidic pH, resulting in a highly viscous solution. At neutral pH and body temperature the viscosity decreases and EMD precipitates. Multilayers of EMD on mineral or protein surfaces have been analysed using ellipsometry, total internal reflection fluorescence (TIRF) and biospecific interaction analysis (BIA). The studies show that EMD adsorbs both to hydroxyapatite and collagen and to denuded dental roots. It forms insoluble spherical complexes, and detectable amounts remain at the site of application on the root surface for two weeks, as shown with radiolabelled protein in rats and pigs. Scanning electron micrograph (SEM) studies on monkey teeth further indicate that EMD in PGA may promote repopulation of fibroblast-like cells during the first weeks after application.

Adsorption↗

PubMed1997

In vitro studies on periodontal ligament cells and enamel matrix derivative.

The recognition that periodontal regeneration can be achieved has resulted in increased efforts focused on understanding the mechanisms and factors required for restoring periodontal tissues so that clinical outcomes of such therapies are more predictable than those currently being used. In vitro models provide an excellent procedure for providing clues as to the mechanisms that may be required for regeneration of tissues. The investigations here were targeted at determining the ability of enamel matrix derivative (EMD) to influence specific properties of periodontal ligament cells in vitro. Properties of cells examined included migration, attachment, proliferation, biosynthetic activity and mineral nodule formation. Immunoassays were done to determine whether or not EMD retained known polypeptide factors. Results demonstrated that EMD under in vitro conditions formed protein aggregates, thereby providing a unique environment for cell-matrix interaction. Under these conditions, EMD: (a) enhanced proliferation of PDL cells, but not of epithelial cells; (b) increased total protein production by PDL cells; (c) promoted mineral nodule formation of PDL cells, as assayed by von Kossa staining; (d) had no significant effect on migration or attachment and spreading of cells within the limits of the assay systems used here. Next, EMD was screened for possible presence of specific molecules including: GM-CSF, calbindin D, EGF, fibronectin, bFGF, gamma-interferon, IL-1 beta, 2, 3, 6; IGF-1,2; NGF, PDGF, TNF, TGF beta. With immunoassays used, none of these molecules were identified in EMD. These in vitro studies support the concept that EMD can act as a positive matrix for cells at a regenerative site.

Calbindins↗

PubMed1997

Clinical safety of enamel matrix derivative (EMDOGAIN) in the treatment of periodontal defects.

The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN at 1 comparable site. In total, 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery, 56 other samples were taken after one treatment with EMDOGAIN, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of postsurgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months postsurgery, and this difference had increased further at the 3 year follow-up. The 2.5-3 mm increase in attachment and bone level after treatment with EMDOGAIN was of the same magnitude as seen in the studies with split-mouth design aiming for test of effectiveness of EMDOGAIN.

Adult↗

PubMed1997

A prospective study of injuries in licensed floorball players.

Injuries occurring among 457 licensed floorball players in the Swedish National League were analysed prospectively during the season from 1993 to 1994. Fifty-one (11%) players sustained 58 injuries. The majority (76%) of the injuries were due to trauma mostly during the gama (55%). Twenty-three (52%) of the traumatic injuries were caused by an opponent or a stick. Ankle sprain (35%) was the most common diagnosis. Injury severity classified with regard to time of absence from sport participation were similarly distributed for minor (36%), moderate (29%) and major (35%) injuries. The total rate of injury was 2.5 per 1000 hours for female and 2.6 for male players. Although this rate is lower than for contact sports like soccer and ice-hockey, we feel that further investigation of floorball injuries and improvement of protection devices would be valuable.

Adult↗

PubMed1997

Effects of heparin coating on the expression of CD11b, CD11c and CD62L by leucocytes in extracorporeal circulation in vitro.

Leucocyte adhesion molecules are involved in the leucocyte-endothelial interaction and in the activation of coagulation and binding of complement and endotoxin. Thus, they are important in inflammation, systemic acute phase reaction, ischaemia reperfusion injury and resistance against infections. The expression of the adhesion molecules CD11b, CD11c and CD62L on leucocytes and changes in plasma products of neutrophil activation (myeloperoxidase, lactoferrin) and complement activation (C3bc, SC5b-9 (TCC)) were examined in an extracorporeal circulation (ECC) model and the effects of Carmeda bioactive surface (CBAS) heparin coating (n = 7) of the circuits were compared to uncoated control circuits (n = 5). In this model, new 'unactivated' cells mobilized from the bone marrow could not interfere with descriptive measures of cell activation as seen in in vivo studies. In the control group, CD11b and CD11c were upregulated on monocytes and granulocytes during ECC, whereas CD62L was downregulated. Heparin coating reduced the increase in CD11b and CD11c on granulocytes (p < 0.02 at 2 h), but the delayed increase in CD11c on monocytes and the delayed downregulation of CD62L on granulocytes and monocytes did not reach statistical significance. Further, heparin coating also reduced the initial decrease in the absolute cell counts of monocytes and granulocytes (p = 0.01 at 2 h), reflecting reduced adhesion to the oxygenator/tubing. The increases in plasma myeloperoxidase, lactoferrin, C3bc and TCC were lower in the heparin-coated group compared to the control group. The increases in plasma myeloperoxidase and lactoferrin correlated significantly to the increase in CD11b (r = 0.71, p = 0.02 and r = 0.64, p = 0.05, respectively) and CD11c (r = 0.72, p = 0.008 and r = 0.72, p = 0.008, respectively) on granulocytes, suggesting interacting regulatory pathways in the process of neutrophil adhesion, activation and degranulation. Thus, in this in vitro ECC model, heparin coating of oxygenator/tubing sets reduced leucocyte activation and leucocyte adhesion-related phenomena.

Blood Cell Count↗

PubMed1997

Continued pregnancy among abortion applications. A study of women having a change of mind.

OBJECTIVE: A certain proportion of women applying for legal abortion later change their minds. The present study was designed to ascertain whether such women differ from those who choose to terminate their pregnancy, with regard to age, civil status, other demographic characteristics, or reproductive history. SETTING: Department of Obstetrics and Gynecology, University Hospital Malmö, Lund University, Sweden. SUBJECTS: All 1,446 abortion applicants attending the abortion clinic at University Hospital Malmö, in 1989. STUDY DESIGN: A comparison of the women who continued the pregnancy and those who underwent abortion, with regard to the above mentioned factors. METHODS: Semistructured interviews and statistical analysis. RESULTS: Of this series of urban abortion applicants, almost one in ten underwent a change of mind. Women who chose to continue their pregnancy differed from those who held fast to their initial decision above all with regard to age and family situation. Less important was education, reproductive history, and stated reasons for abortion. CONCLUSIONS: To answer the question why some women continue an unwanted pregnancy after a closer consideration is not easy. The complexity of a woman's feeling in the matter seems to be moderated by the kind of support and stability she has in her life situation and also of the stability in relation to her partner. An equally important question is whether this change of mind is associated with a changed attitude to the expected baby (i.e., does an unwanted child become a wanted one?).

Abortion Applicants↗

PubMed1996

Centrifugal pump and heparin coating improves cardiopulmonary bypass biocompatibility.

BACKGROUND: Centrifugal pumps are being used increasingly for short-term extracorporeal circulation purposes such as during heart operations. Whether the centrifugal pump improves the cardiopulmonary bypass biocompatibility has not been fully documented. METHODS: A roller pump (n = 20) was compared in vivo with a centrifugal pump (n = 20) in groups of patients in which cardiopulmonary bypass circuits that were either totally heparin coated (Carmeda BioActive Surface; n = 20) or uncoated (n = 20) were used. We expected the heparin coating to attenuate blood activation, thus possibly making the comparison of the two pumps easier with respect to their different blood activation potentials. Samples of blood plasma, obtained during cardiopulmonary bypass from low-risk coronary artery bypass grafting patients, were analyzed for hemolysis (plasma haemoglobin), complement activation (C3bc and the terminal complement complex), a complement lytic inhibitor (vitronectin), coagulation activation (fibrinopeptide A), granulocyte activation (lactoferrin), and platelet activation (beta-thromboglobulin). RESULTS: The concentrations of terminal complement complex, lactoferrin, and beta-thromboglobulin were significantly lower in association with heparin-coated surfaces. The concentration of plasma hemoglobin was significantly lower in association with the centrifugal pump. In uncoated circuits, the beta-thromboglobulin level was significantly higher in association with the roller pump than with the centrifugal pump, but this significant reduction in the beta-thromboglobulin level did not hold true for the heparin-coated circuit group. CONCLUSIONS: A heparin-coated cardiopulmonary bypass surface reduces the blood activation potential during cardiopulmonary bypass, and the centrifugal pump causes less hemolysis than the roller pump.

Adult↗

PubMed1996

Dopaminergic transmission in the rat retina: evidence for volume transmission.

The study was designed to determine whether dopaminergic neurotransmission in the retina can operate via volume transmission. In double immunolabelling experiments, a mismatch as well as a match was demonstrated in the rat retina between tyrosine hydroxylase (TH) and dopamine (DA) immunoreactive (ir) terminals and cell bodies and dopamine D2 receptor-like ir cell bodies and processes. The match regions were located in the inner nuclear and plexiform layers (D2 ir cell bodies plus processes). The mismatch regions were located in the ganglion cell layer, the outer plexiform layer, and the outer segment of the photoreceptor layer, where very few TH ir terminals can be found in relation to the D2 like ir processes. In similar experiments analyzing D1 receptor like ir processes versus TH ir nerve terminals, mainly a mismatch in their distribution could be demonstrated, with the D1 like ir processes present in the outer plexiform layer and the outer segment where a mismatch in D2 like receptors also exists. The demonstration of a mismatch between the localization of the TH terminal plexus and the dopamine D2 and D1 receptor subtypes in the outer plexiform layer, the outer segment and the ganglion cell layer (only D2 immunoreactivity (IR)) suggests that dopamine, mainly from the inner plexiform layer, may reach the D2 and D1 mismatch receptors via diffusion in the extracellular space. After injecting dopamine into the corpus vitreum, dopamine diffuses through the retina, and strong catecholamine (CA) fluorescence appears in the entire inner plexiform layer and the entire outer plexiform layer, representing the match and mismatch DA receptor areas, respectively. The DA is probably bound to D1 and D2 receptors in both plexiform layers, since the DA receptor antagonist chlorpromazine fully blocks the appearance of the DA fluorescence, while only a partial blockade is found after haloperidol treatment which mainly blocks D2 receptors. These results indicate that the amacrine and/or interplexiform DA cells, with sparse branches in the outer plexiform layer, can operate via volume transmission in the rat retina to influence the outer plexiform layer and the outer segment, as well as other layers of the rat retina such as the ganglion cell layer.

Animals↗

PubMed1996

The epidemiology of hepatocellular carcinoma in patients with acute intermittent porphyria.

OBJECTIVE: To describe the epidemiology, pathogenesis and clinical features of hepatocellular carcinoma (HCC) in patients with acute intermittent porphyria (AIP). DESIGN: A retrospective population-based mortality study. SUBJECTS: All inhabitants who died between 1978-1990 (2122) including 33 with AIP, in two municipalities in northern Sweden with a high prevalence of AIP. INTERVENTIONS: Death certificates and hospital records were examined. Histological re-examination of paraffin-embedded specimens from patients with HCC was performed and hepatitis B virus content analysed. RESULTS: HCC was found in 27% of patients with AIP versus 0.2% of the deceased non-AIP subjects, P < 0.0001. HCC was more common in women (men:women 1:2) and in manifest AIP (manifest: latent 2:1). Liver cirrhosis was more common in AIP patients (12%), especially in women, compared with controls (0.5%), P < 0.0001. CONCLUSIONS: AIP patients seem to have an increased risk of developing HCC. This tumour is more common in patients with manifest AIP and in women, a reversal of the usually reported gender ratio for HCC. No cause for developing HCC other than AIP was found. The pathogenesis may be explained by abnormalities in porphyrin metabolism and by intrinsic production of mutagenic substances, resulting in a condition of systemic overload of oxidative stress, enhancing mutation rate and liver cell injury. Liver cirrhosis appears to be more common in AIP patients and may be a preliminary stage to HCC. All AIP gene carriers aged > or = 55 should be screened for HCC.

Aged↗

PubMed1996

Assessment of autonomic nerve function in acute intermittent porphyria; a study based on spectral analysis of heart rate variability.

OBJECTIVES: To assess the function of the autonomic nervous system in patients with acute intermittent porphyria by spectral analysis of the heart rate variability. DESIGN: A cross-sectional case-control study. SETTING: Patients were examined at the Primary Health Care Centre, Arjeplog and at Umeå University Hospital, where the controls were also examined. SUBJECTS: Twenty-three patients with acute intermittent porphyria verified by DNA analysis and 92 healthy controls were included. MAIN OUTCOME MEASURES: The mid-frequency band power after tilting was used to evaluate sympathetic function, and the high frequency band power during controlled breathing at 12 breaths min-1 and the mid-frequency band power during controlled deep breathing at 6 breaths min-1 were used to evaluate parasympathetic function. RESULTS: There was no evidence of sympathetic dysfunction in the patients. The mid-frequency band power during controlled deep breathing at 6 breaths min-1 was significantly (P = 0.02) lower in the patient group. CONCLUSIONS: Our findings indicate a parasympathetic dysfunction in patients with acute intermittent porphyria. This may be causally related to sudden cardiac death and the life-threatening arrhythmias which have been observed in this disorder.

Adult↗

PubMed1996

Isolation and characterization of a trisulfide variant of recombinant human growth hormone formed during expression in Escherichia coli.

A new variant of human growth hormone was recently found [Pavlu, B. & Gellerfors, P. (1993) Bioseparation 3, 257-265]. We report here the identification and the structural determination of this variant. The variant, which is formed during the expression of human growth hormone in Escherichia coli, was found to be more hydrophobic than rhGH as judged by its prolonged elution time by hydrophobic interaction chromatography. The rhGH hydrophobic variant (rhGH-HV) was isolated and subjected to trypsin digestion and RP-HPLC analysis, resulting in an altered retention time of one single tryptic peptide as compared to the corresponding fragment of rhGH. This tryptic peptide constitutes the C-terminus (aa 179-191) of hGH and contains one of the two disulfide bridges in hGH, viz. Cys182-Cys189. Amino acid sequences and composition analyses of the tryptic peptide from rhGH-HV (Tv18-19) and the corresponding tryptic peptide from rhGH (T18+19) were identical. Electrospray mass spectrometry (ES MS) of Tv18+19 isolated from rhGH-HV revealed a monoisotopic mass increase of 32.7, as compared to T18+19 from rhGH. A synthetic Tv18+19 peptide having a trisulfide bridge between Cys182 and Cys189 showed identical fragment in ES/MS compared to Tv18+19 isolated from rhGH-HV, i.e. m/z 617.7 and 682.9. These fragments are formed through a unique cleavage in the trisulfide (Cys182-SSS-Cys189) bridge not found in the corresponding T18+19 disulfide peptide. Furthermore, the synthetic Tv18+19 co-eluted in RP-HPLC with Tv18+19 isolated from rhGH-HV. Two-dimensional NMR spectroscopy of the synthetic T18+19 and Tv18+19 peptides were performed. Using these data all protons were assigned. The major chemical shift changes (delta delta > 0.05 ppm) observed were for the beta-protons of Cys182 and Cys189 in Tv18+19 as compared to T18+19. CD spectroscopy data were also in agreement with the above results. Based on these physico-chemical data rhGH-HV has been structurally defined as a trisulfide variant of rhGH. The receptor binding properties of rhGH-HV was studied by a biosensor device, BIAcore. The binding capacity of rhGH-HV was similar to rhGH with a binding stoichiometry to the rhGHBP of 1:1.6 and 1:1.5, respectively, indicating that the trisulfide modification did not affect its receptor binding properties.

Amino Acid Sequence↗

PubMed1996

Allergy development and macromolecular absorption in infants with different feeding regimens during the first three days of life. A three-year prospective follow-up.

A group of 129 infants were randomly assigned at birth to one of three feeding regimens: human milk (HM), cow's milk formula (CMF) or a casein hydrolysate formula (CHF) during the first 3 days of life. Blood samples were taken on at 4 days and at 2, 4, 8, 12 and 24 months of age. Macromolecular absorption was analysed by measuring the serum concentration of human alpha-lactalbumin (S-alpha-LA) with a competitive radioimmunoassay (RIA). Total serum IgE was measured by RIA. A family history of allergy correlated to the proportion of infants with allergic symptoms both at 24 and 36 months of age (p = 0.03 and p = 0.04 respectively). In none of the three groups did correlation exist between the duration of breastfeeding and serum alpha-LA, serum IgE, family history of allergy, frequency of allergic symptoms and proportion of infants with infections.

Animals↗

PubMed1996

Differences in blood activation related to roller/centrifugal pumps and heparin-coated/uncoated surfaces in a cardiopulmonary bypass model circuit.

An in vitro model cardiopulmonary bypass (CPB) circuit consisting ot tubing, oxygenator and venous reservoirs with either a roller or a centrifugal pump, and with either heparin-coated (Carmeda Bioactive Surface, CBAS) or uncoated surfaces, was studied with respect to 'blood activation', using small-scale-based blood volume (450 + 500 ml). Sixteen circuits were tested in each pump group, eight with and eight without heparin-coated surfaces, by circulating heparinized fresh human blood for 72 hours at 30 degrees C. Blood plasma, sampled at defined intervals, was analysed for haemolysis (lactate dehydrogenase and potassium), complement activation (C3bc and C5b-9 (TCC)), complement lytic inhibitors (vitronectin and clusterin), coagulation activation (fibrinopeptide A), granulocyte (lactoferrin and myeloperoxidase) and platelet (beta-thromboglobulin) activation and contaminating endotoxin. The heparin coating significantly reduced the concentrations of C3bc, TCC, fibrinopeptide A, lactoferrin, myeloperoxidase and beta-thromboglobulin. The two pump types did not differ with respect to these parameters, but the roller pump caused significantly higher increases in plasma LDH and potassium and significantly greater reductions in clusterin and vitronectin than the centrifugal pump. Endotoxin concentration was low at the start and after 24 hours in all groups. These results confirm that heparin-coated CPB surfaces reduce blood activation, and suggest that centrifugal pumps cause less haemolysis and less reduction in lytic complement inhibitors than roller pumps.

Blood Coagulation↗

PubMed1996

Oestrogen receptor analysis of paraffin sections and cytosol samples of primary breast cancer in relation to outcome after adjuvant tamoxifen treatment. The South Sweden Breast Cancer Group.

The aim of the present study was to compare oestrogen receptor (ER) analysis results obtained in cytosols of frozen breast cancer tissue (using biochemical assay) with those obtained in paraffin-embedded tissue (using immunoperoxidase staining with monoclonal antibodies (DAKO-ER, 1D5), and an ER positivity cut-off level of >10% stained nuclei). In 86% (84/98) of the samples the same ER status (28 negative and 56 positive) was obtained with both procedures. In eight cases, the paraffin section was ER positive but the corresponding cytosol sample ER negative, whereas six cases showed the opposite pattern. The ER positive subgroup manifested better outcome after adjuvant treatment than the ER negative subgroup (p = 0.003 (cytosol), and p = 0.004 (paraffin)). As compared with the percentage of stained nuclei, staining intensity yielded no additional information. Although the results of ER analysis of paraffin-embedded material seem promising, it is too early to prefer it to frozen tissue, though this would be useful when no frozen tissue is available.

Aged↗

PubMed1996

Hepatocellular carcinoma in patients from northern Sweden with acute intermittent porphyria: morphology and mutations.

More than a decade ago an association between acute intermittent porphyria (AIP) and hepatocellular carcinoma (HCC) was reported, but still the cause of the increased prevalence is unknown. Paraffin sections of formalin-fixed HCC from 17 AIP patients were reexamined and also screened for relevant mutations using several methods. The tumor diagnosis was verified, and in several cases precirrhosis and cirrhosis were also found. The clinically founded AIP diagnosis was verified at the gene level in most cases, demonstrating the Norrland type of mutation, i.e., G(593)-to-A substitution in codon 198 of the porphobilinogen deaminase (PBGD) gene. The second allele was neither mutated nor missing, contradicting the possibility that the PBGD gene might function as a tumor suppressor gene. Subsequent sequencing showed that cases not cleaved by the restriction enzyme NheI lacked the specific Norrland mutation. In recent years, selective mutations at codons 249 and 166 of the p53 gene have been described in HCC associated with aflatoxin and hepatitis B virus. In our area, with low exposure to those agents, no mutations in codon 249 were found, and mutation in codon 166 was excluded in all tumors except one; no traces of hepatitis B DNA were observed. Nor did we find mutations in H-ras 12 or 61. Intrinsic aberrations in AIP, including reduced heme synthesis and endogenous oxidative damage to DNA, may incite carcinogenic mutations elsewhere in the genome of liver cells. The increased cell proliferation coupled to precirrhosis and cirrhosis perhaps represents promotion in the initiation-promotion sequence of hepatocarcinogenesis.

Adenine↗

PubMed1995

Microsomal glutathione transferase: lipid-derived substrates and lipid dependence.

Rat liver microsomal glutathione transferase was found to display glutathione peroxidase activity toward a variety of oxidized lipids. 1-Linoleoyl-2-palmitoyl phosphatidylcholine hydroperoxide, 2-linoleoyl-1-palmitoyl phosphatidylcholine hydroperoxide, 2-linoleoyl-1-palmitoyl phosphatidylethanolamine hydroperoxide, and cholesteryl linoleate hydroperoxide all served as substrates (0.02, 0.04, 0.02, and 0.02 mumol/min mg, respectively). The phospholipid hydroperoxide glutathione peroxidase activity of the enzyme was found not to require detergent and increased when liposomes containing peroxidized phospholipid were fused with liposomes containing microsomal glutathione transferase. Methyl linoleate ozonide serves as a very efficient substrate for the microsomal glutathione transferase. The unactivated and N-ethylmaleimide-activated enzyme displayed specific activities of 0.74 and 5.9 mumol/min mg, respectively. Upon examination of a series of 4-hydroxyalk-2-enals it was found that the catalytic efficiency of the enzyme increases from the 4-hydroxyhept-2-enal up to the 4-hydroxytetradec-2-enal. The specific activities with the various 4-hydroxyalk-2-enals tested varied between 0.28 and 0.95 mumol/min mg. The phospholipid dependence of the microsomal glutathione transferase was examined in proteoliposomes formed by cholate dialysis. Phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine, and rat liver microsomal phospholipids could all be used successfully to reconstitute the enzyme. In conclusion, microsomal glutathione transferase can detoxify a number of lipid peroxidation products as well as a fatty acid ozonide. The results imply a protective role for the enzyme under conditions of oxidative stress.

Animals↗