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M Farstad

Publications and source records attributed to M Farstad.

At least 19 recordsLinked to original sources
PubMed1992

The activities of acyl-CoA:1-acyl-lysophospholipid acyltransferase(s) in human platelets.

The activities of acyl-CoA:1-acyl-lysophospholipid acyltransferases (EC 2.3.1.23) have been studied in human platelet lysates by using endogenously formed [14C]acyl-CoA from [14C]fatty acid, ATP and CoA in the presence of 1-acyl-lysophosphatidyl-choline (lysoPC), -ethanolamine (lysoPE), -serine (lysoPS) or -inositol (lysoPI). Linoleic acid as fatty acid substrate had the highest affinity to acyl-CoA:1-acyl-lysophospholipid acyltransferase with lysoPC as variable substrate, followed by eicosapentaenoic acid (EPA) and arachidonic acid (AA). The activity at optimal conditions was 7.4, 7.3 and 7.2 nmol/min per 10(9) platelets with lysoPC as substrate, with linoleic acid, AA and EPA respectively. EPA and AA were incorporated into all lyso-forms. Linoleic acid was also incorporated into lysoPE at a high rate, but less into lysoPS and lysoPI. DHA was incorporated into lysoPC and lysoPE, but only slightly into lysoPI and lysoPS. Whereas incorporation of all fatty acids tested was maximal for lysoPC and lysoPI at 200 and 80 microM respectively, maximal incorporation needed over 500 microM for lysoPE and lysoPS. The optimal concentration for [14C]fatty acid substrates was in the range 15-150 microM for all lysophospholipids. Competition experiments with equimolar concentrations of either lysoPC and lysoPI or lysoPE resulted in formation of [14C]PC almost as if lysoPI or lysoPE were not added to the assay medium.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1992

The activity and subcellular distribution of the peroxisomal enzyme acyl-CoA oxidase in human blood platelets.

The peroxisomal enzyme acyl-CoA oxidase is localized in the 'dense-tubular-system-enriched fraction', probably identical with the endoplasmic reticulum, in human blood platelets. This localization is strongly different from the localization of catalase which seems to be a cytosolic enzyme, in agreement with Marcus, Zucker-Franklin, Safir & Ullman [(1966) J. Clin. Invest. 45, 14-28]. A localization of acyl-CoA oxidase in the endoplasmic reticulum seems to be in good accordance with the important role of peroxisomes in the metabolism of prostaglandins, as recently demonstrated by Diczfalusy, Kase, Alexson & Bjørkhem [(1991) J. Clin. Invest. 88, 978-984].

Acyl-CoA Oxidase↗
PubMed1992

Sixty minutes normothermic ischemia in rat liver: the declining tissue concentration of hypoxanthine during reperfusion is not a washout phenomenon.

A rat liver normothermic ischemia-reperfusion model was used to investigate whether hypoxanthine (HXA) that accumulated during ischemia was washed out in hepatic veins during reperfusion. Ischemia was induced in median and left lobes by clamping of the proper hepatic artery and portal branches. The effect of allopurinol (ALL) on metabolism of ATP and HXA was studied before, during and after a 60-min normothermic ischemic insult. Liver cell concentration of HXA in the group treated with ALL increased during ischemia and decreased rapidly during the first 10-min reperfusion. Recovery of ATP increased gradually during the 10-min reperfusion period and was significantly higher in the group treated by ALL compared to that of controls. Liver venous blood concentration of HXA in the ALL-treated group was 10-to 40-fold lower than that in liver tissue. The rapidly decreasing concentration of HXA in liver tissue during reperfusion and a minimal washout may indicate that HXA was used for resynthesis of ATP during reperfusion.

Adenosine Triphosphate↗
PubMed1991

Identity between palmitoyl-CoA synthetase and arachidonoyl-CoA synthetase in human platelet?

Apparent Km values have been determined for the substrates ATP, CoA and fatty acids for the long-chain acyl-CoA synthetase (EC 6.2.1.3) reaction in lysates of human blood platelets. The apparent Km for ATP was higher for saturated fatty acids (C12:0 to C18:0) than for unsaturated acids (C18:1 to C22:6). Other apparent Km values were very similar for all long-chain fatty acids tested. Palmitic acid inhibited the formation of [14C]arachidonoyl-CoA, and arachidonic acid inhibited the formation of [14C]palmitoyl-CoA, with [14C]arachidonate or [14C]palmitate respectively as substrate. After chromatography of Triton X-100-extracted platelet protein in several systems (hydroxyapatite, DEAE-Sepharose, Sephacryl S-200 HR, CoA-Sepharose, Sephadex G-100 and AcA 34), both arachidonoyl-CoA synthetase and palmitoyl-CoA synthetase activities were eluted together in the various protein peaks, and with approximately the same ratio of activities in all peaks. After some purification steps (DEAE-Sepharose and Sephacryl S-200 HR), the acyl-CoA synthetase activity was up to 37 nmol/min per mg of protein with [14C]palmitate as substrate, and up to 116 nmol/min per mg of protein with [14C]arachidonate as substrate. The purification was respectively about 8- and 10-fold. The results indicate that palmitoyl-CoA (or unspecific) synthetase and arachidonoyl-CoA (or specific) synthetase are in fact the same enzyme, in agreement with previously reported results from this laboratory.

Blood Platelets↗
PubMed1991

Fatty acids in human platelets and plasma. Fish oils decrease sensitivity toward N2 microbubbles.

Platelet aggregation induced by N2 microbubbles (simulating microbubbles developed during deep diving) was measured in seven volunteers before and after intake of ethyl-eicosapentaenoate (-EPA, 3.5 g/day) and ethyl-docosahexaenoate (-DHA, 2.5 g/day) for 2 wk. The relative content of arachidonic acid (AA) decreased in platelets from all individuals, whereas the content of EPA and DHA increased. The decrease of AA was almost identical with the increase of EPA plus DHA. In plasma the AA content was unchanged, while EPA and DHA increased. The N2 microbubble-induced aggregation showed a significant negative correlation with the DHA content both in platelets and in plasma. Less aggregation was also observed with high EPA content in platelets or plasma. A significant correlation between AA content in platelets and aggregation was seen. Intake of marine oils may be beneficial to divers under deep diving and to patients during extracorporeal circulation, because this may reduce the microbubble-induced aggregation.

Adult↗
PubMed1991

Sixty-minute normothermic liver ischemia in rats. Evidence that allopurinol improves liver cell energy metabolism during reperfusion but that timing of drug administration is important.

Allopurinol (ALL) improves energy metabolism in organs subjected to ischemia-reperfusion injury. The importance of different administration schedules of ALL has been studied in a rat liver model exposed to 60 min of normothermic ischemia followed by reperfusion. ALL (100 mg/kg) that administered in two doses, one prior to ischemia and one prior to reperfusion, improved production of adenosine triphosphate in the liver as well as bile flow during reperfusion. ALL administered in a single dose, either prior to ischemia or prior to reperfusion, was less effective. The concentration of hypoxanthine during ischemia increased in the groups given ALL prior to induction of ischemia. Based on the present findings, we argue that the beneficial effect of ALL administration can be potentiated by different drug-administration schedules. Our data also suggest that the prime mechanism of action for ALL is not only related to inhibition of free-oxygen-radicals production but that preservation of hypoxanthine, which can be used for ATP resynthesis and the scavenging properties of ALL itself, may be equally important.

Adenosine Triphosphate↗
PubMed1990

[Prostate-specific antigen. A new biological serum marker for prostatic adenocarcinoma].

Prostate-specific antigen (PSA) was measured by polyclonal radioimmunoassay in 45 untreated patients with prostatic cancer and 14 patients with benign prostatic hyperplasia. Prostatic acid phosphatase (PAP) was determined in 35 patients with prostatic cancer and 14 patients with benign hyperplasia. Serum PSA was raised in 42 patients with cancer of the prostate, but only 14 of 35 patients showed increased serum levels of PAP. Half the patients with benign prostate hyperplasia had PSA greater than 4 micrograms/l and one third had PSA greater than 10 micrograms/l. PAP was slightly elevated in two patients with benign prostatic hyperplasia. Serum PSA increased with the clinical stage of prostatic cancer. However, preoperative levels of PSA were not sufficiently reliable to predict the final pathological stage for each individual patient. After radical prostatectomy for cancer confined to the prostate, serum PSA fell to an undetectable level.

Acid Phosphatase↗
PubMed1990

Detection of malignant tumours by multivariate analysis of proton magnetic resonance spectra of serum.

Proton magnetic resonance spectra of blood serum have been subjected to multivariate data analysis to discriminate between samples from cancer patients and from controls. The main feature was the use of digitally defined resonance profiles. The methyl and methylene lipoprotein signals centred at 1.3 and 0.9 parts per million are non-lorentzian composite peaks that cannot be described properly by the line width at half-height. Instead 71 and 76 data points were used to describe the methylene and methyl peak profiles, respectively. These data points were used as input to a principal component analysis to distinguish between malignant (n = 29) and control samples (n = 55). At a probability level of 0.01 (F-test) modelling classified all patients except 2 correctly, while 1 control was slightly above the predictive level for malignancy.

Female↗
PubMed1990

60 min normothermic liver ischemia in rats: allopurinol improves energy status and bile flow during reperfusion.

The effect of allopurinol was studied in a normothermic liver ischemia rat model. Functional (bile flow) and biochemical parameters (high-energy phosphates, ATP, ADP, AMP), energy charge, hypoxanthine and xanthine were determined prior to and during 60 min of ischemia followed by 120 min of reperfusion. Allopurinol given in the preischemic period (50%) and as a bolus (50%) prior to reperfusion improved liver function significantly, whereas allopurinol given in the preischemic period (50%) and after start of reperfusion (50%) had no effect. The data indicates that allopurinol given prior to reperfusion saved hypoxanthine which was used for ATP resynthesis during reperfusion.

Adenosine Triphosphate↗
PubMed1990

Thrombin-induced serotonin release as an in vitro indicator of the functional integrity of stored platelets.

Measurements of endogenous serotonin and the thrombin-induced serotonin release reaction in platelet concentrates were compared with other methods of quality control: particle counting and pH and gas analyses. A discrepancy between the serotonin release reaction and the other data was observed after seven days of storage. The decline in the release reaction was not predictable from pH measurements or the number of platelets or leukocytes in the concentrate. There was a significant positive correlation between endogenous serotonin content and the thrombin-induced serotonin secretion after seven days of storage. We conclude that the current methods for routine control of platelet concentrates may not ensure the quality of the product after it has been stored for seven days. The thrombin-induced serotonin release may provide a valuable addition to the battery of tests available.

Blood Gas Analysis↗
PubMed1989

Identical subcellular distribution of palmitoyl-CoA and arachidonoyl-CoA synthetase activities in human blood platelets.

Fractionation of human blood platelets showed that palmitoyl-CoA synthetase and arachidonoyl-CoA synthetase activities had an identical distribution among subcellular fractions. The activity was highest with arachidonic acid as substrate in all fractions, with an enzyme activity of 50 nmol/min per mg of protein, in a 'dense-tubular-system'-enriched fraction. The ratio activities with arachidonate and palmitate as substrates was about 1.5 in all fractions. Heat inactivation did not distinguish between arachidonoyl-CoA synthetase and a palmitoyl-CoA synthetase. On the other hand, heat inactivation indicated two pools of long-chain acyl-CoA synthetases: one in a mitochondria- and one in the dense-tubular-system-enriched fraction.

Blood Platelets↗
PubMed1989

Sixty minutes of normothermic ischemia in the rat liver: correlation between adenine nucleotides and bile excretion.

The effect of 60 min of normothermic liver ischemia on cellular levels of adenine nucleotides (ATP, ADP, and AMP), energy charge (EC), and bile excretion was studied. Following ischemia the concentration of ATP was reduced to 12% of preischemic and control values within the first 10 min and remained low during the remaining ischemic period. EC values were also low. During 120 min of reperfusion, ATP increased to 34% of the ATP level found in the control group. EC values increased immediately to reach values not significantly different from those of control animals. Bile flow was nonexistent during ischemia and increased during reperfusion. The increase paralleled those of ATP and EC. Bile flow seems to reflect the degree of liver ischemia and may be used as a functional parameter.

Adenine Nucleotides↗
PubMed1988

Ethionine-induced alterations of enzymes involved in lipid metabolism and their possible relationship to induction of fatty liver.

Changes of enzymes involved in the hepatic metabolism of long-chain fatty acids (palmitoyl-CoA synthetase (EC 6.2.1.3), carnitine palmitoyltransferase (EC 6.2.1.3), glycerophosphate acyltransferase (EC 2.3.1.15)) in the liver of male rats were examined after ethionine exposure. Ethionine administration resulted in a dose- and time-dependent enhancement of the palmitoyl-CoA synthetase activity both in the mitochondrial, peroxisomal and microsomal fractions. The total carnitine palmitoyltransferase activity in the mitochondrial fraction was enhanced. Ethionine administration was also associated with dose- and time-dependent changes of the microsomal glycerophosphate acyltransferase activity, whereas the mitochondrial enzyme activity was marginally affected. The hepatic triacylglycerol content of the ethionine-treated animals was increased. Hepatic lipids were accumulated in large droplets. Serum triacylglycerol and cholesterol were decreased. In particular, the serum HDL-cholesterol level was lowered. The concentration of ATP in the liver decreased. Accumulation of the metabolic product S-adenosylethionine (AdoEth) was observed for the first 2 days of exposure followed by a fall in S-adenosylmethionine (Ado-Met) during the next 10 days. Linear regression analysis of ATP content versus AdoEth and AdoMet showed highly significant correlations. A significant correlation between the hepatic triacylglycerol and AdoEth content was also observed upon ethionine treatment. The data show that ethionine perturbs the hepatic lipid metabolism. Enhanced esterification of long-chain fatty acids, but not a simple reduction of their oxidation, might contribute to ethionine-induced fatty liver in addition to a block in secretion of lipoproteins and decreased protein synthesis.

Acyltransferases↗
PubMed1987

Effect of volume depletion on the afferent arterioles in the avian kidney.

Nine white leghorn chickens were injected i.m. with furosemide (10 to 60 mg/kg body weight) twice daily for 18 days. The birds were then anesthetized with a combination of equithesin and diazepam and the kidneys perfused via the heart. Kidney tissue was sectioned serially and the granular epithelioid cells were counted in the juxtaglomerular apparatuses of the furosemide treated birds and in 3 normal chickens. Hyperplasia and hypergranulation of the epithelioid cells was found to occur in the juxtaglomerular apparatuses of both mammalian and reptilian type nephrons (with and without Henles loop) in the furosemide treated group. This finding was interpreted as an effect of hypovolaemia on the juxtaglomerular apparatuses. Furosemide caused an immediate stop in weight gain, an increase in the erythrocyte volume fraction and a sudden drop in blood pressure. The blood pressure later rose to subnormal levels. The heart rate was not altered. Plasma sodium and chloride fell significantly one day after furosemide administration and remained low throughout the experiment. Potassium fell during the second part of the experimental period. Captopril was injected after 18 days of furosemide treatment and lowered the blood pressure significantly. This was interpreted as indirect evidence for the presence of renin in the granular epithelioid cells and indicates the importance of the renin angiotensin system in maintaining the blood pressure in hypovolaemic conditions.

Animals↗
PubMed1979

Intracellular localization of long-chain acyl-coenzyme A hydrolase and acyl-L-carnitine hydrolase in brown adipose tissue from guinea pigs.

The activities of long-chain acyl-CoA hydrolase (palmitoyl-CoA hydrolase, EC 3.1.2.2) and long-chain acyl-L-carnitine hydrolase, EC 3.1.1.28) in brown adipose tissue from cold-exposed and control guinea pigs were studied. Mitochondria from cold-exposed animals hydrolysed 21 nmol of palmitoyl-CoA/min per mg of protein and 1.3 nmol of palmitoyl-L-carnitine/min per mg of protein, and the specific activities were respectively 2 and 5 times as high in cold-exposed as in control animals. The subcellular-localization studies showed that both the long-chain acyl-CoA hydrolase and long-chain acyl-L-carnitine hydrolase were localized in the mitochondria. A location also in the soluble fraction cannot be excluded. The long-chain acyl-CoA hydrolase activity was doubled when the mitochondria were disrupted; this indicates that the enzyme is localized in the matrix compartment.

Adipose Tissue, Brown↗