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Biomedical subjects

M Andersson

Publications and source records attributed to M Andersson.

At least 235 records · Page 13Linked to original sources

Elastase inhibitory capacity of purified canine alpha-1-antitrypsin.

In a previous study, isoelectrofocusing of serum from liver-diseased and healthy dogs revealed three different types of the acute phase protein, alpha-1-antitrypsin: Pi (protease inhibitor) F, Pi I and Pi S. Moreover, accumulated alpha-1-antitrypsin was found immunohistochemically in liver sections from dogs with chronic liver disease, predominantly in association with Pi I in serum. The present study was made to further the relationship between alpha-1-antitrypsin and the pathogenesis of chronic liver disease in dogs. Aliquots of samples of purified canine Pi F, Pi I and Pi S were examined for elastase inhibitory capacity, the main function of alpha-l-antitrypsin, and for polymerization tendency, a possible cause of accumulation of alpha-1-antitrypsin in the liver. These parameters were studied after incubation of the proteins at different temperatures (4, 37 and 42 degrees C) and pH values (6.8, 7.8 and 8.5) and for different periods (< or = 24 h and 5 days). In contrast to findings with Pi Z, the human alpha-1-antitrypsin variant associated with liver disease, polymers of canine Pi F, Pi I or Pi S could not be detected under any of the conditions tested. However, Pi I was sensitive to pH, as was demonstrated by reduced elastase inhibitory capacity after incubation at pH 6.8 for < or = 24 h or 5 days, or at pH 8.5 for 5 days. However, after incubation at pH 7.8 for < or = 24 h or 5 days at 4, 37 or 42 degrees C, Pi I was completely stable. Pi F retained its elastase inhibitory capacity, even after prolonged incubation, at all pH values and temperatures tested. Due to low yield, Pi S was tested only after incubation for < or = 24 h at pH 6.8 and at 4 degrees C; under these conditions its elastase inhibitory capacity was equal to that of Pi F. Taken together, these findings indicate molecular and functional differences between Pi I and Pi F and further support a role for alpha-1-antitrypsin in the pathogenesis of canine liver disease.

Animals↗

Accuracy of machine milling and spark erosion with a CAD/CAM system.

A method for manufacturing crowns and fixed partial dentures based on CAD/CAM has been developed as an alternative to the lost wax technique and the casting of an alloy. In this process two steps are included: milling and spark erosion. The computer-assisted design (CAD) relies heavily on the accuracy of the milling and spark erosion processes to achieve a clinically acceptable restoration. These two processes must be able to produce the crown data generated in the CAD files. This study evaluated the accuracy of the Procera CAD/CAM system in creating specific geometric bodies that were compared with the known dimensions in the CAD files for these bodies. The manufacturing errors of milling (ellipse +/- 6.5 microm, square +/- 3.4 microm, and cylinder +/- 5.8 microm) and spark erosion (ellipse +/- 8.6 microm and square +/- 10.4 microm) were determined. The accuracy of this manufacturing process demonstrated that this system was capable of producing a crown with a clinically accepted range for marginal opening gap dimension of less than 100 microm.

Analysis of Variance↗

NK-lysin, structure and function of a novel effector molecule of porcine T and NK cells.

NK-lysin (NKL), a 78-residue antimicrobial peptide, was isolated from pig small intestine. Standard methods identified the peptide as basic, with six half-cystine residues in three intrachain disulphide bonds. The sequence showed 33% identity with a part of a putative gene product (NKG5) from activated T and NK cells, NK-lysin showed antibacterial activity against Escherichia coli and Bacillus megaterium and marked lytic activity against YAC-1, a NK sensitive tumour cell line, while sheep red blood cells were unaffected. The cDNA clone corresponding to NK-lysin has been characterized. We have also analyzed the cell and tissue specific expression and the induction of the gene. A lymphocyte fraction enriched in T and NK cells, stimulated by human interleukin-2 (IL-2), showed a 30-fold increase of the NKL transcript. NK-lysin specific mRNA is also detectable in spleen, bone marrow and colon. Immunostaining showed NKL to be present in different types of lymphocytes. Our results strongly suggest that NK-lysin is involved in the inducible cytotoxicity of T and NK cells.

Animals↗

Lovastatin inhibits interferon-gamma-induced Trypanosoma brucei brucei proliferation: evidence for mevalonate pathway involvement.

Interferon-gamma (IFN-gamma) is an essential immunoregulating molecule that has recently been shown to have a growth stimulatory effect on Trypanosoma brucei brucei (T. b. brucei). The signalling pathway(s) involved during this triggering are unknown. Since the different products from the biosynthesis pathway utilizing mevalonate have several important cellular functions, ranging from cholesterol synthesis to growth control, we here investigate the possible role for the mevalonate pathway in IFN-gamma-driven parasite proliferation. Thus, lovastatin, a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug, was incubated at different concentrations in vitro with T. b. brucei. The parasites were then stimulated with a broad concentration range of rIFN-gamma. The effect on proliferation or growth was measured either by the tritium-labeled thymidine incorporation assay or by direct counting of parasites from the cultures using light microscopy. The maximum proliferative response was obtained with IFN-gamma at a concentration of 10(3) U/ml added to 10(6) parasites. This response was markedly decreased with lovastatin, even at a low concentration (0.1 mM). The effect of lovastatin was reversed by the addition of 10 mM mevalonate. IFN-gamma at a concentration of 10(4) U/ml showed no proliferative effect. Addition of mevalonate to this concentration of IFN-gamma gave a threefold increase in parasite proliferation. Our data suggest that a low concentration of IFN-gamma induces parasite growth, a high concentration has the opposite effect, and both these events are regulated by activity or inactivity of the mevalonate pathway.

Animals↗

Effects of amino acids on synthesis and degradation of skeletal muscle proteins in humans.

Synthesis and degradation of globular and myofibrillar proteins across arm and leg muscles were examined during stepwise increased intravenous infusion of amino acids (0.1, 0.2, 0.4, and 0.8 g N.kg-1.day-1) to healthy volunteers. Protein dynamics were measured by a primed constant infusion of L-[ring-2H5]phenylalanine and the release of 3-methylhistidine from skeletal muscles. Arterial concentrations and flux of glucose, lactate, and free fatty acids were unchanged despite increasing concentrations of plasma amino acids from 2.6 to 5.7 mM. Plasma insulin, insulin-like growth factor I (IGF-I), and plasma concentrations of IGF-I-binding proteins-1 and -3 remained at fasting levels throughout the investigation. Amino acid infusion caused a significant uptake of the majority of amino acids across arm and leg tissues, except tyrosine, tryptophan, and cysteine, probably due to low concentrations of these amino acids in the formulation. The balance of globular proteins improved significantly (P < 0.01) due to stimulation of synthesis and attenuation of degradation across arm and leg tissues, despite insignificant uptake of tyrosine, tryptophan, and cysteine. Degradation of myofibrillar proteins was uninfluenced by provision of amino acids. The results demonstrate that neither insulin nor circulating IGF-I explained improved protein balance in skeletal muscles after elevation of plasma amino acids. Rather, some amino acids in themselves trigger cellular reactions that initiate peptide formation. Limited availability of some extracellular amino acids was overcome by increased reutilization of the intracellular amino acid.

Adult↗

Calpains in the human lens: relations to membranes and possible role in cataract formation.

Calpains are Ca-activated neutral proteases present in all cells together with an endogenous inhibitor, calpastatin. Proposed substrates are; cytoskeletal proteins like microtubules and actin, protein kinases such as PKC and membrane-bound enzymes like Ca-ATPase and the Ca-channel. In lenses from different species calpains have been detected in decreasing amounts from the epithelium to the cortex to the nucleus. Several substrates for calpain in the lens have been demonstrated: crystallins, vimentin, actin, beaded filaments and MP26 among others. Both studies on animal models and capsulorhexis indicate that calpains are mainly involved in cortical cataract.

Calcium↗

Immediate and late adverse reactions in coronary angiography. A comparison between iodixanol and ioxaglate.

PURPOSE AND METHODS: In 120 patients in a double-blind, randomized, pa rallel study, iodixanol (Visipaque), a nonionic dimer isotonic with blood, was compared with ioxaglate (Hexabrix), an ionic low-osmolar dimer, in coronary angiography regarding early and late adverse reactions. Haemodynamic and electrophysiologic parameters were also analyzed. RESULTS: Visipaque resulted in significantly fewer early adverse contrast medium-related reactions (p<0.05). Visipaque also demonstrated significantly fewer effects on electrophysiologic parameters. Both contrast media reduced systolic and diastolic blood pressures at the 1st injection in the left coronary artery. Late adverse reactions were unusual with both contrast media and occurred only as urticaria with a frequency of 1.7%, which is lower than reported in i.v. studies. One serious adverse reaction, a myocardial infarction in a male patient with severe cardiovascular disease, occurred in the Visipaque group. This event was considered to be procedure- and disease-related rather than related to the type of contrast medium used. CONCLUSION: We found Visipaque safe for coronary angiography, causing fewer early adverse reactions than Hexabrix and also fewer effects on electrophysiologic parameters. Late adverse reactions seemed to be unusual with intra-arterial administration of contrast media.

Contrast Media↗

Day-night differences in mucosal plasma proteins in common cold.

Aggravation of symptoms in inflammatory airway diseases is common in the early morning hours, but little is known about day-night differences in the occurrence of plasma exudate on the airway surface. We have therefore examined the plasma macromolecules on the nasal mucosa at different time points. The study comprised 20 subjects who had been inoculated (day 0) with coronavirus intranasally. Ten subjects remained healthy and 10 developed common cold with significant symptoms from day 2 to day 6. Starting on day 3 at 8.00 h and repeated at 4 h intervals until 4.00 h on day 4, nasal lavages were carried out by employment of a nasal pool-device which fills the entire unilateral nasal cavity and gently but effectively irrigates its surface. Lavage fluid levels of albumin (Mw 69,000 D) and fibrinogen (Mw 340,000 D) were determined. In the healthy subjects the levels of albumin and fibrinogen remained low throughout the experiment, however, with mean peak values of the two proteins occurring at 4.00 h (p < 0.05 compared to daytime nadir at 16.00 h). In subjects with common cold both albumin (p < 0.05) and fibrinogen (p < 0.01) exhibited marked variation with individual and mean peak levels recorded at 8.00 h day 3, and 4.00 h day 4. These mean peak values were 5-20 times higher (p < 0.01 - p < 0.05) than the mean levels recorded in these subjects at the other time periods. The present data indicate a marked day-night difference in the occurrence of plasma proteins on the airway surface in common cold, whereas in health the difference is much less. We conclude that different-sized plasma proteins may accumulate on the mucosa in healthy airways during late night hours and that in common cold this nocturnal accumulation may be considerably increased.

Adult↗

Respect for the patient's integrity and self-determination--an ethical imperative called upon in the Swedish Health and Medical Care Act.

The Swedish Health and Medical Care Act of 1983, states that health and medical care should be based on respect for the patient's self determination and integrity. The aim of this statement according to the legislative preparatory work, was to ensure that individuals seeking help from the health care system retained their dignity and integrity. The law also states that care, when possible, is to be planned and implemented in consultation with the patient. The statement in the Act, can be seen as an ethical principle that expresses an ideal. Since the concepts of integrity were found to be used vaguely and ambiguously, clarification was required in order to facilitate a discussion about how respect for the patient's integrity ought to be realized. A research study was performed where the aim was to find a fruitful definition of integrity and to suggest criteria that delineate the characteristics of a good health-care professional, who is willing and able to respect the patient's integrity.

Ethics, Medical↗

Structural studies of the extracellular polysaccharide from Butyrivibrio fibrisolvens strain 49.

The structure of Butyrivibrio fibrisolvens strain 49 capsular polysaccharide has been investigated mainly by sugar and methylation analysis, partial chemical degradations, NMR spectroscopy, and mass spectrometry. The results suggest that the polysaccharide is composed of pentasaccharide repeating units having the following structure. [formula: see text] The polysaccharide contains O-acetyl groups, one of which is substituted to O-3 of the 4-substituted alpha-D-Galp residue, while others occur in non-stoichiometric amounts at other locations.

Bacterial Capsules↗

Lung carcinoma and malignant mesothelioma in patients exposed to Thorotrast: incidence, histology and p53 status.

In a previous registry-based survey of 999 patients injected with alpha-emitting 232ThO2 (Thorotrast), we identified elevated risks for lung carcinoma and malignant mesothelioma. Since injected Thorotrast is retained lifelong mostly in liver, spleen and lymph nodes, the mesothelial surfaces of these organs are constantly irradiated. Thorotrast-administered patients also perpetually exhale 220Rn, a 232Th-daughter. Study of Thorotrast-exposed patients may, therefore, provide data with regard to carcinogenicity of radon exposure, a current public health concern, as well as the pathogenesis of malignant mesothelioma. The incidence and histologic types of lung carcinoma and malignant mesothelioma within the cohort were examined by review of available histopathologic material and medical records. Further, mutations of the p53 gene were analyzed whenever possible as it has previously been suggested that radon-associated lung carcinomas exhibit specific mutational patterns. The cumulative risk for lung carcinoma reached 11.0% based on 20 confirmed cases. Nine were small cell lung cancer (SCLC), whereas the expected frequency was 18%. The risk for malignant mesothelioma reached 2.5% based on 7 cases. The actuarial risk of malignant mesothelioma for patients given more than 20 ml Thorotrast was 7.8% compared to 1.4% for patients administered smaller amounts. Seven lung carcinomas and 5 malignant mesotheliomas were analyzed for p53 mutations; only 1 (in a lung adenocarcinoma) was detected. A possible association between Thorotrast and SCLC is suggested. In addition, a possible dose-response gradient exists for Thorotrast and malignant mesothelioma.

Adolescent↗

Age-dependent modifications in the metabolism of mevalonate pathway lipids in rat brain.

The levels and rates of biosynthesis of mevalonate pathway lipids in rat brain were investigated during development and aging. Between birth and 18 months of age there are only moderate decreases in the phospholipid and cholesterol contents but an increase in the levels of dolichyl-P and, particularly of dolichol. The amount of ubiquinone is unchanged. The rate of incorporation of [3H]leucine into protein decreases by 10% during the first year, while the incorporation of [3H]glycerol into phospholipids decreases by 20%. The high rates of [3H]mevalonate incorporation into cholesterol and dolichol after birth decreases rapidly. In contrast, the rate of incorporation into ubiquinone is constant. Squalene synthase activity decreases rapidly in the early postnatal period and at 18 months of age this activity is 10-fold lower than immediately after birth. cis-Prenyltransferase activity is also high during the first postnatal month and reaches a constant level at 4 months of age. Significantly, nonaprenyl 4-hydroxybenzoate transferase activity is high during the entire period investigated. The rate of lipid peroxidation does not change during aging. These results demonstrate that brain cholesterol and dolichol exhibit a low rate of turnover during aging, whereas ubiquinone is synthesized at a high rate and exhibits rapid turnover throughout the entire lifespan.

Aging↗

NK-lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity.

A 78 residue antimicrobial, basic peptide, NK-lysin, with three intrachain disulfide bonds was purified from pig small intestine and characterized. A corresponding clone was isolated from a porcine bone marrow cDNA library. The 780 bp DNA sequence had a reading frame of 129 amino acids which corresponded to NK-lysin. The clone was used to show that stimulation with human interleukin-2 induced synthesis of NK-lysin-specific mRNA in a lymphocyte fraction enriched for T and NK cells. Lower levels of mRNA were detected in tissues known to contain T and NK cells, such as small intestine, spleen and colon. Interleukin-2 also induced both proliferation of the lymphocyte fraction and cytolytic function in these cells. Immunostaining showed that NK-lysin was present in cells positive for CD8, CD2 and CD4. NK-lysin showed high anti-bacterial activity against Escherichia coli and Bacillus megaterium and moderate activity against Acinetobacter calcoaceticus and Streptococcus pyogenes. The peptide showed a marked lytic activity against an NK-sensitive mouse tumour cell line, YAC-1, but it did not lyse red blood cells. The amino acid sequence of NK-lysin exhibits 33% identity with a putative human preproprotein, NKG5, of unknown function but derived from a cDNA clone of activated NK cells. We suggest that NK-lysin is a new effector molecule of cytotoxic T and NK cells.

Amino Acid Sequence↗

An amphipathic helical motif common to tumourolytic polypeptide NK-lysin and pulmonary surfactant polypeptide SP-B.

The tumour-lysing and antimicrobial polypeptide NK-lysin and the pulmonary surfactant-associated polypeptide SP-B exhibit 24% residue identities (49% similarities), including six half-cystine residues in the same disulphide bonding pattern, and similar far-UV circular dichroism spectra corresponding to 45-55% alpha-helix and 20-25% beta-sheet structures. From this, we conclude that the conformations of NK-lysin and SP-B are similar. In contrast, the functional properties of the two proteins are dissimilar: SP-B does not exhibit antibacterial activity and NK-lysin does not significantly effect phospholipid spreading at an air/water interface. Saposins, which solubilize lipids and activate lysosomal hydrolases, the pore-forming amoebapores, and parts of acid sphingomyelinase and acyloxyacylhydrolase, also share 18-27% sequence identities with NK-lysin (and SP-B), including the six conserved half-cystine residues. The inclusion of NK-lysin extends the family of saposin-like polypeptides, all members of which appear to interact with lipids. Strictly conserved structural features with implications for helix topology and lipid interactions are observed.

1,2-Dipalmitoylphosphatidylcholine↗