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Biomedical subjects

A Nilsson

Publications and source records attributed to A Nilsson.

At least 343 records · Page 19Linked to original sources

Hydrolysis of chylomicron polyenoic fatty acid esters with lipoprotein lipase and hepatic lipase.

The lipolysis of rat chylomicron polyenoic fatty acid esters with bovine milk lipoprotein lipase and human hepatic lipase was examined in vitro. Chylomicrons obtained after feeding fish oil or soy bean oil emulsions were used as substrates. The lipolysis was followed by gas chromatography or by using chylomicrons containing radioactive fatty acids. Lipoprotein lipase hydrolyzed eicosapentaenoic (20:5) and arachidonic acid (20:4) esters at a slower rate than the C14-C18 acid esters. More 20:5 and 20:4 thus accumulated in remaining tri- and diacylglycerols. Eicosatrienoic, docosatrienoic and docosahexanoic acids exhibited an intermediate lipolysis pattern. When added together with lipoprotein lipase, hepatic lipase increased the rate of lipolysis of 20:5 and 20:4 esters of both tri- and diacylglycerols. Addition of NaCl (final concentration 1 M) during the course of lipolysis inhibited lipoprotein lipase as well as the enhancing effect of hepatic lipase on triacylglycerol lipolysis. Hepatic lipase however, hydrolyzed diacylglycerol that had already been formed. Chylomicron 20:4 and 20:5 esters thus exhibit a relative resistance to lipoprotein lipase. It is suggested that the tri- and diacylglycerol species containing these fatty acids may accumulate at the surface of the remnant particles and act as substrate for hepatic lipase during a concerted action of this enzyme and lipoprotein lipase.

Animals↗

Phosphorylation regulates the activity of the eEF-2-specific Ca(2+)- and calmodulin-dependent protein kinase III.

The activity of the eukaryotic elongation factor 2 (eEF-2)-specific Ca(2+)- and calmodulin-dependent protein kinase III (CaM PK III) is regulated by phosphorylation. The kinase can be inactivated by treatment with alkaline phosphatase and subsequently reactivated by endogenous protein kinase. This kinase can be substituted for by the catalytic subunit of cAMP-dependent protein kinase but not by casein kinase II. The purified kinase preparation contains only one protein as judged by gel electrophoresis. This protein has a molecular mass of approximately 90 kDa and an isoelectric point of 5.2. Reactivation of the eEF-2 kinase is associated with the phosphorylation of this protein. The amino acid sequence obtained from the 90-kDa protein reveals substantial homology with that of murine heat shock protein 86 (HSP 86) a member of the HSP 90-family. Conventional preparations of HSP 90 contain an inactive eEF-2 kinase that could be activated after dephosphorylation and phosphorylation by the catalytic subunit of cAMP-dependent protein kinase.

Alkaline Phosphatase↗

Regulation of chylomicron remnant uptake in the human hepatoma cell-line Hep G2. Role of the low-density lipoprotein receptor.

Uptake and degradation of chylomicron remnants by the human hepatoma cell line Hep G2 was studied. Mesenteric lymph was collected from rats and injected into hepatectomized rats to obtain chylomicron remnants. This remnant preparation was taken up and catabolized by Hep G2 cells. The uptake process was dependent on cell growth and was regulated by compactin (a HMG-CoA reductase inhibitor) which suppresses cholesterol synthesis and by mevalonolactone, which enhances cholesterol synthesis. A monoclonal anti LDL receptor antibody blocked binding of chylomicron remnants to Hep G2 cells to a degree, which was comparable to but generally lower than the suppression of low-density lipoprotein binding. The results thus indicate that in Hep G2 cells, chylomicron remnant uptake is regulated, similarly to low-density lipoprotein uptake and that a significant part of the remnant uptake is mediated through the LDL receptor.

Antibodies, Monoclonal↗

[Influenza and death. High mortality not only due to the great epidemics].

Excess mortality in a population is one of the hallmarks of an influenza epidemic. Apart from the pandemic years, 1918-1919, 1957 and 1968-1969, annual excess mortality has occurred 16 times in Sweden during the period 1911-1988. An unusually high mortality was caused by Influenza A Sichuan 2/87 (H3N2), the unexpected appearance of which at the beginning of November 1988 started an intensive epidemic in Sweden, while other European countries had a relatively mild influenza season. Swedish deaths in December totalled 10,500-2,200 more than expected; age groups over 65 years accounted for 95 per cent of the mortality, and those over 80 (N = 350,000 in Sweden) for 1,400 deaths. 0.4 percent of those over 80 died. The excess mortality is to be explained by the high proportion of the elderly in the Swedish population and the very low rate of influenza vaccination before the outbreak. As the increase in the proportion of the very elderly can be expected to continue, future influenza epidemics will result in even higher mortality unless adequate prophylactic measures are taken.

Adult↗

Fourier-transform infrared spectroscopy study of dioleoylphosphatidylcholine and monooleoylglycerol in lamellar and cubic liquid crystals.

The liquid-crystalline phases of the systems monooleoylglycerol (MO)/water, dioleoylphosphatidylcholine (DOPC)/water, and MO/DOPC/water have been studied by Fourier-transform infrared (FTIR) spectroscopy. In the latter ternary system, the sn-3 OH group of MO competes with water to interact with the polar head group of DOPC, and an intramolecular hydrogen bonding of MO is broken up. The hydration of the ester carbonyl groups in the lamellar phases of both the MO/water and DOPC/water systems increases with increasing water content. Similarly, the addition of small amounts either of MO to a DOPC/water system or of DOPC to an MO/water system also results in an increase in the hydration of the ester carbonyl groups. This leads to an unfavorable hydrocarbon-water contact which is counteracted by the formation of a cubic phase, except for the DOPC/water system, where the lamellar phase is stable also at the highest water concentrations. The phase behavior of the different systems can be described in terms of lipid monolayer curvature and molecular packing in the lipid aggregates. Finally, it is shown by the water association band in the FTIR spectrum that the water hydrogen bonding is considerably different in the liquid-crystalline phases than in bulk water.

Fourier Analysis↗

Kinetic characterisation of the enzymatic activity of the eEF-2-specific Ca2(+)-and calmodulin-dependent protein kinase III purified from rabbit reticulocytes.

The Ca2(+)-and calmodulin-dependent protein kinase III, which specifically phosphorylates the eukaryotic elongation factor 2 (eEF-2), has been purified to apparent homogeneity from the post-ribosomal fraction of rabbit reticulocytes by an efficient four-step method. The method results in a more than 4000-fold purification of the enzyme. SDS-gel electrophoresis showed that the purified kinase contained only one polypeptide with the apparent molecular mass of 90 kDa. The kinase activity was associated with the 90-kDa protein as shown by analyzing the phosphorylating activity of SDS gel electrophoretically purified protein electroblotted to nitrocellulose membranes. The purified kinase was dependent on Ca2+, Mg2+ and calmodulin for activity. Kinetic analysis of the phosphorylation reaction indicates that the turnover number of the kinase was approximately 1 s-1. The Km for the two substrates ATP and eEF-2 was calculated to be approximately 100 microM and 10 microM, respectively. The activity of the kinase was competitively inhibited by cAMP. The inhibition constant Ki (0.5 mM) was found to be in the same order of magnitude as that calculated for the competitive product inhibition caused by ADP. GTP was ten-times less efficient as competitor, indicating that the kinase had a preference for adenosine nucleotides. Phosphorylation of eEF-2 did not interfere with the diphtheria-toxin-catalysed ADP-ribosylation of the factor nor did ADP-ribosylation inhibit phosphorylation.

Adenosine Diphosphate↗

Exposure to dioxins and dibenzofurans through the consumption of fish.

BACKGROUND: In some regions, including the Baltic Sea, fatty fish such as salmon and herring contain high levels of polychlorinated dibenzodioxins and dibenzofurans. We investigated human exposure to these potentially toxic substances in relation to the consumption of fish from the Baltic Sea. METHODS: Plasma levels of 10 different dibenzofurans and 7 dioxins were analyzed in three groups of Swedish men: one group with a high intake of fish (fish eaten almost daily; n = 11), one with a moderate intake of fish (about once per week; n = 9), and one with no consumption of fish (usually because of allergy; n = 9). RESULTS: Plasma levels of several of the compounds we measured were higher in the men with a high intake of fish than in those who consumed moderate amounts, and the levels were higher in those who ate moderate amounts of fish than in those who ate none. The median amounts of the most toxic dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) were 8.0 pg per gram of plasma lipid (range, 2.0 to 13) in the high-intake group, 2.6 pg per gram (range, 1.2 to 4.2) in the moderate-intake group, and 1.8 pg per gram (range, 1.0 to 2.5) in the nonconsumers (P = 0.001 and 0.02, respectively). There were consistent and statistically significant associations between the reported amount of fish eaten and the plasma levels of several of the dibenzofurans and dioxins. CONCLUSIONS: Contaminated fish such as those from the Baltic Sea are an important source of exposure to polychlorinated dibenzofurans and dibenzodioxins in persons who eat fish regularly. However, the clinical consequences of such exposure remain uncertain.

Adult↗

Regulation of cartilage growth by growth hormone and insulin-like growth factor I.

A number of studies have shown that growth hormone (GH) and insulin-like growth factor-I (IGF-I) have important regulatory roles for skeletal growth. However, it has been a matter of controversy whether GH acts directly on cells in the growth plate or if the growth-promoting effects of GH are mediated by liver-derived (endocrine-acting) IGF-I. With the recognition that GH regulates the production of IGF-I in multiple extra-hepatic tissues, autocrine and paracrine functions of IGF-I have been suggested as important components of GH action. This review focuses on recent developments in our understanding of the cellular mechanisms by which GH promotes longitudinal bone growth and the inter-relationship between GH and IGF-I in the growth plate.

Animals↗

On the pathogenesis of abnormal involuntary movements in lithium-treated patients with major affective disorder.

Abnormal involuntary movements during long-term lithium treatment were investigated on two occasions, 7 years apart, in 37 outpatients with major affective disorder according to DSM-III. The patients had been on continuous lithium treatment for an average of 8.2 years when entering the study, and all had been exposed to neuroleptics. Psychiatric status and side effects were evaluated, and abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale (AIMS). Signs of abnormal involuntary movements were age-dependent and seen in 8% of the patients at the initial investigation in 1980, and the proportion of affected individuals had increased by 16% by the end of the study in 1987. Women above the age of 50 (in which category the frequency of abnormal involuntary movements was 38%) were selected for further analysis. Severe abnormal involuntary movements in this category were associated with the early onset of affective illness, low body weight, the occurrence of dementia among first-degree relatives, and with high 12-h lithium levels.

Adult↗

Effects of amperozide in schizophrenia. An open study of a potent 5-HT2 receptor antagonist.

Ten male inpatients (aged 29 +/- 6 years) with a DSM-III diagnosis of schizophrenia participated in a 4-week open dose escalation study of amperozide, a novel 5-HT2 receptor antagonist. The maximum daily dose of amperozide was 20 mg. A close dose-plasma concentration relationship showed considerable interindividual variation in the steady-state plasma levels at a given dose. Approximately equal concentrations of amperozide and its metabolite, N-deethylated amperozide, were seen in plasma. The prolactin levels were not increased during amperozide treatment. No changes occurred in hematological or other laboratory parameters. ECG showed changes in T-wave morphology and a prolongation of the QTc time. One patient was withdrawn from the trial due to aggravation of psychotic symptoms, and two patients had a brief, temporary discontinuation of the drug due to somatic illness. Six patients were improved during amperozide treatment, as assessed by the Clinical Global Improvement Scale. Among the responders the total CPRS was reduced by a mean of 64% and total BPRS score by a mean of 46%. Mild tremor was a frequent side effect, but other extrapyramidal symptoms were rare. Nausea was seen in six patients and of a more pronounced character in one patient. In general, the severity of the side effects increased with increasing doses of amperozide.

Adult↗

Premedication before elective breast surgery, a comparison between ketobemidone and midazolam.

One hundred female patients scheduled for elective breast surgery (mean age 60 +/- 11 years were randomly assigned to receive one of two premedications: ketobemidone (Ketogan) 1-1.5 ml or midazolam 4-5 mg, intramuscularly. The effects on preoperative anxiety and postoperative emetic sequelae were studied. All patients were anaesthetised with thiopentone, fentanyl and atracurium, and ventilated with a mixture of nitrous oxide in oxygen with supplementary isoflurane. Sixty-nine percent of the midazolam- and 50% of the ketobemidone-premedicated patients experienced a reduction in anxiety. Midazolam was found to be more effective than ketobemidone in reducing anxiety among more tense patients--those with a VAS grading before premedication of 2 or more (P less than 0.05). Midazolam-premedicated patients were also assessed by observers as being more relaxed (P less than 0.05). No difference was seen in the frequency of emetic sequelae: 20 patients in the midazolam group and 14 patients in the ketobemidone group vomited once or more during the 24-h observation period. There was no difference between the two groups in time until an analgetic was required. In conclusion, midazolam seemed more effective in reducing preoperative anxiety than ketobemidone without any negative effects on postoperative emesis or time until an analgetic was required.

Aged↗

Lithium discontinuers. II. Therapeutic outcome.

Eleven patients from a lithium-treated cohort of 64 patients with major affective disorder (DSM-III) were investigated after a mean of 6.7 years on lithium prophylaxis and reinvestigated 7 years later, at which point they had discontinued lithium for a mean of 2.3 years. Therapeutic outcome was compared in the 11 discontinuers and 20 continuers on lithium from the same cohort, matched for sex, age, and mental status on admission to the study. Ratings of psychopathology (CPRS) at the end of the 7-year follow-up period showed that the only significant difference between the patient categories was a higher frequency of reported autonomic disturbances and worry over trifles in the discontinuers. Daily doses of neuroleptic drugs were significantly higher in discontinuers than in controls by the end of the study. Alternative concomitant treatment outside conventional medicine was sought by 45% of the discontinuers, whereas no lithium-treated control reported the need for such additional therapeutic measures.

Antipsychotic Agents↗

Expression and physiological significance of growth hormone receptors and growth hormone binding proteins in rat and man.

The molecular structure of the GH receptor has recently been characterized and the receptor identified as a member of a new receptor superfamily that includes the prolactin receptor and several cytokine receptors. No obvious signal transducing domain has been identified on any of these related receptors. One possible signalling mechanism involves receptor interaction with other membrane-associated proteins that function as mediators of signal transduction. Whether such a mechanism is involved in signal transduction of the GH receptor is not known. Another common feature of these receptors is the presence of soluble forms such as the GHBP. The functions of these proteins in the circulation and at the level of the target cell remain to be resolved.

Animals↗

Pancreatic lipolytic enzymes in human duodenal contents. Radioimmunoassay compared with enzyme activity.

The total pancreatic lipolytic capacity was determined in duodenal contents in healthy humans 10-120 min after a liquid test meal, by estimating the amount of pancreatic lipase, colipase, carboxyl ester lipase, and phospholipase A2 by means of radioimmunoassays and enzymatic assays. The molar concentrations of the different proteins were of the same order of magnitude. The relative specific activity (enzyme activity/milligram immunoreactive protein expressed as a percentage of the specific activity of the respective pure protein) amounted to 75-120% for lipase, 45-80% for colipase, 30-70% for carboxyl ester lipase, and 45-120% for phospholipase A2. These varied, and sometimes low values can be explained by the fact that the enzymes are inhibited or partly inactivated in the duodenal contents by surface denaturation, in which cases the products are still immunoreactive. Also, the proforms of colipase and phospholipase A2 may not always be completely activated. Furthermore, the specific activities of the pure enzymes (and thus the relative specific activities) are related to the methods used, which are not specific enough to distinguish completely the three enzymes and the cofactor in duodenal contents.

Adult↗

Cultivation of HL-60 cells in a serum-free medium containing granulocyte/macrophage colony-stimulating factor.

In order to develop a defined cultivation medium for HL-60 cells, we cultivated these cells in a serum-free suspension medium and tested the effect of various growth factors. Of the factors tested, granulocyte/macrophage colony-stimulating factor was most active in growth stimulation. A much lower effect was obtained with granulocyte colony-stimulating factor and transferrin. No effect was found with interleukin-3 and insulin. Granulocyte colony-stimulating factor was the only growth factor tested that also induced differentiation as judged by the nitroblue tetrazolium test. Growth of HL-60 cells in medium containing granulocyte/macrophage colony-stimulating factor (125 U/ml) and transferrin (5 micrograms/ml) as the only protein factors was similar to growth in medium containing 10% serum. No increase in spontaneous differentiation of HL-60 cells in this defined medium was observed. Physiological concentrations of retinol bound to retinol-binding protein and retinyl ester in chylomicron remnants reduced proliferation as well as the level of c-myc oncoprotein and induced differentiation of HL-60 cells cultivated in defined medium. Hence, this defined medium may be useful when studying the function of retinoids in HL-60 cells.

Animals↗