Biomedical subjects

G Ronquist

Publications and source records attributed to G Ronquist.

At least 109 records · Page 6Linked to original sources

PubMed1993

alpha-Amino-n-butyric acid methyl ester induces concentrative uptake of L-dopa in human Langerhans' cells normally not operative for L-dopa transport.

We recently reported the existence of two kinds of human epidermal Langerhans' cells (LC), one which can take up and accumulate L-dopa and one which cannot. The dopa(+) LC take up L-dopa by carrier-mediated exchange diffusion, that is, the influx of L-dopa and the outflow of an intracellular substance are linked via the same carrier. The nature of the fundamental difference between L-dopa(+) and L-dopa(-) cells has not been clarified. We have now found that alpha-amino-n-butyric acid methyl ester (ABA-OME) penetrates into intracellular compartments, perhaps endosomes or lysosomes, of all LC, where hydrolysis results in the accumulation of the free amino acid (ABA). This accumulation causes a considerable increase in osmotic pressure of the membrane-limited organelle, leading to influx of water and swelling. Co-incubation with L-dopa revealed an influx of L-dopa into LC which normally cannot take up this amino acid. It is suggested that these LC lack the capacity to synthesize and/or store the counterpart which allows L-dopa to enter the dopa(+) LC, but that ABA in the L-dopa(-) LC can function as an equivalent counterpart.

Adult↗

PubMed1993

Ionophore A23187 reduces energy charge by enhanced ion pumping in suspended human erythrocytes.

Washed human erythrocytes were basically incubated in phosphate-buffered saline at 37 degrees C with different concentrations (1-5 mumol l-1) of the divalent cationophore A23187. This ionophore induced a decrease by about 75% of ATP content and energy charge (EC) and a concomitant increase in ADP and AMP contents in a dose-dependent fashion such that an inverse ATP/ADP relationship developed. EGTA at 1 mumol l-1 annihilated the effect of A23187 on energy status. When glucose was added to the basic incubation medium A23187 inclusion resulted in an elevated lactate production concomitantly with a partial restoration of EC. Introduction of Mg2+ to basic incubation medium containing glucose and the ionophore resulted in a sharp increase in lactate production with an energy state that was maintained at a control level. It is concluded that the low EC of erythrocytes obtained by this ionophore is the result of runaway ATPases dissociated from glycolysis. Since human erythrocytes are devoid of organelles other than the plasma membrane it is concluded that the ionophoric effect is exerted in the plasma membrane.

Adenosine Diphosphate↗

PubMed1993

Effects of the ionophore gramicidin D on energy metabolism in human erythrocytes.

Washed human erythrocytes were incubated in phosphate-buffered saline at 37 degrees C with different concentrations (2-80 mg l-1) of the monovalent cationophore gramicidin D. The ionophore induced a decrease of ATP content and energy charge (EC) and a concomitant increase in ADP and AMP contents. At a concentration of 10 mg l-1 of the ionophore the reduction of EC and ATP concentration was about 50%. Increasing the concentration of the ionophore resulted in a substantial haemolysis with no further effect on the nucleotide levels. Lowering the concentration of the ionophore to 5 mg l-1 (to avoid haemolysis) lead to a similar effect on the energy status. Ouabain at 0.5 mmol l-1 in incubation medium distinctly blunted the ionophoric effect on EC and adenine nucleotides. Addition of glucose on the contrary reversed these effects by about 80%. Hence, the glucose-induced increase in glycolytic flux as evidenced by an increase in lactate production was not sufficient to restore energy state.

Adenosine Diphosphate↗

PubMed1993

Increased activity of 5' nucleotidase in serum of patients with sickle cell anaemia.

Fifty-nine patients with homozygous sickle cell anaemia, 17 heterozygous individuals and 22 controls were investigated in respect to serum (S) 5'nucleotidase (5'NT, EC 3.1.3.5). The patients showed a significantly higher mean value of S-5'NT compared to the controls. However, this rise was heterogeneous as it occurred only among a subgroup of patients. The heterozygous individuals were not different from either the patients or the controls generating a situation which puts the heterozygous individuals in an intermediate position between the patients and the controls. S-5'NT showed significant correlation with S-bilirubin, S-aspartate aminotransferase, S-alanine aminotransferase and especially S-gammaglutamyl transferase. However, it was not correlated with S-alkaline phosphatase, which is another marker for hepatobiliary disease. These results suggest that the liver involvement in a subgroup of patients with sickle cell anaemia is a mixture of hepatocyte damage and the biliary tree involvement.

5'-Nucleotidase↗

PubMed1993

Ionophoric interaction with the myocyte sarcolemma: a new insight into the pathophysiology of degenerative myocardial disease.

A certain group of compounds often derived from microbes known as ionophores function as ion channels when incorporated in biological membranes. Different ionophores have a relative specificity for certain cations such as Ca2+ or K+. When such compounds are integrated in the cell membrane of a host cell a leakage of the ion in question is induced and the physiologic ion gradient will be dissipated. This will activate ion pumps at the expense of ATP in order to restore the physiologic ion gradient. This effect is seen for a number of different viruses including Coxsackie B3. Based on own experiments we suggest that this ionophoric effect is important in the pathophysiology of myocarditis. We have shown that mice with Coxsackie B3 myocarditis have low myocardial ATP and high ADP and AMP levels. This pattern of abnormal energy metabolism is also seen in patients with Syndrome X. It is suggested that the ECG and thallium perfusion scintigram suggestive of ischemia in such patients is rather due to the effect of an ionophore leading to an extracellular potassium shift.

Adenine Nucleotides↗

PubMed1992

Increased membrane activity of glyceraldehyde 3-phosphate dehydrogenase in erythrocytes of patients with homozygous sickle cell anaemia.

Membrane-bound glyceraldehyde 3-phosphate dehydrogenase activity was measured in erythrocytes from 43 patients with sickle cell anaemia, 24 heterozygous and 27 controls. A significant increase of the activity was found among the patients but no such difference was observed between the heterozygous and the control individuals. The patients showed nearly non Gaussian distribution of the enzyme activity and were subgrouped on the basis of these results, subgroup I had normal values and subgroup II showed markedly increased activities. The patients in subgroup II had significantly lower blood haemoglobin concentrations and significantly higher lactate dehydrogenase activities in serum than subgroup I. The subgroups did not differ in blood reticulocyte counts, serum bilirubin, serum iron concentrations or band 3 protein content of erythrocyte membranes.

Adolescent↗

PubMed1992

Membrane transport properties of L-2,4-diaminobutyrate revisited.

We explore here the special structural features of certain diamino acid analogs which may account for their intense accumulation into tumor cells, first observed for the Ehrlich ascites tumor cell for in vitro suspensions. This accumulation, which ordinarily occurs mainly by system A for its dipolar substrates, is so intense for these tripolar diamino acids accompanied by the chloride ion as well as by displacement, especially of the cellular potassium ion, that the cells swell to several times their normal volume and osmotic destruction arises. These structural features receive our reconsideration here toward understanding the energization of amino acid transport into cells, also toward identifying among them possible superior 11C-labeled tracers for imaging tumors in situ by positron emission tomography (PET). The possibility of therapeutic, perhaps osmotic, destruction of inoperable terminal gliomas by topical application of such amino acids by microdialysis has also been considered in preliminary tests by one of us (G.R.) and his associates.

Amino Acids↗

PubMed1992

Treatment of malignant glioma by a new therapeutic principle.

L-2, 4 diaminobutyric acid (DAB) is a non-physiological, cationic amino acid transported into cells by System A with potent antitumour activity in vitro against human glioma cells. This activity was the result of the pronounced concentrated uptake of DAB in glioma cells to the extent that a cellular lysis could occur due to osmotic reasons. We describe the treatment of 3 patients with inoperable malignant glioma by direct and continuous administration of DAB in tumour tissue employing a microdialysis technique. One to three microdialysis probes were implanted in the tumour tissue through small dural incisions in 3 patients with inoperable malignant glioma. Micropumps charged with 3 ml a day of a Tris-buffered 0.125 M DAB solution made isotonic at pH 7.55 were adapted to the input channel of the probe and a sampling tube to the output for continuous flowing into tumour tissue. The patients were treated in this way for a total of 14-21 days without side effects assignable to DAB. Massive tumour necrosis occurred as judged by comparison of computed tomography performed before and after DAB treatment. The yield of the dialysis procedure with regard to DAB was estimated to be 40-50%. The dialysate concentration of arginine (a cationic amino acid considered to be transported mainly by system A) was high and increased nearly 4-fold from day 3 to day 6 of treatment. DAB administered in this way into malignant brain tumour tissue was well tolerated and showed promising antitumour activity in the 3 patients with inoperable malignant glioma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminobutyrates↗

PubMed1992

Influence of beta 1-blockade on myocardial substrates early after a coronary operation.

A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. This study was undertaken to find out if early postoperative high-dose infusion of the selective beta 1-blocking agent metoprolol tartrate has additional effects on metabolic variables related to myocardial energy supply/demand balance compared with those obtained with a late preoperative oral dose. The study included 21 male patients undergoing coronary bypass grafting. All patients received an oral dose of metoprolol before the operation. After the operation, patients were randomized to a control group or a group receiving intravenous infusion of metoprolol. Myocardial uptake of oxygen and substrates was determined before and during atrial pacing. Metoprolol reduced arterial concentrations of free fatty acids, reduced myocardial uptake of free fatty acids, and enhanced myocardial uptake of lactate. During paced tachycardia, the metoprolol concentration correlated negatively with myocardial uptake of free fatty acids (r = -0.80; p < 0.001) and positively with myocardial uptake of lactate (r = 0.53; p < 0.05). It is concluded that postoperative infusion of metoprolol induces myocardial metabolic changes compatible with an improved energy supply/demand balance.

Administration, Oral↗

PubMed1992

Biochemical and functional effects of creatine phosphate in cardioplegic solution during aortic valve surgery--a clinical study.

During myocardial ischemia there is a drop in high-energy phosphates in the myocardium. Cold potassium cardioplegia decreases but does not altogether prevent this reduction. Supplementation of cardioplegic solutions with the high-energy compound creatine phosphate (10 mmol/L) compared to plain cardioplegic solutions was investigated in this study. Thirty patients scheduled for aortic valve replacement were included. The patients were randomized to group I (creatine phosphate) or group II (control). Postoperative hemodynamic evaluation revealed no significant differences between the groups. However, group I exhibited a tendency toward a better stroke-work index (135 +/- 18% vs. 102 +/- 5% recovery 15 minutes after bypass and 145 +/- 16% vs. 119 +/- 11% recovery 105 min after bypass). There were fewer patients in group I (5/15) needing inotropic support compared to group II (9/14). The myocardial content of ATP and creatine phosphate showed no significant differences during ischemia and reperfusion. It is concluded that the myocardial protection during ischemia was sufficient to prevent significant reductions of myocardial ATP and creatine phosphate irrespective of supplementation with CP.

Adenosine Triphosphate↗

PubMed1992

Lack of evidence for altered complement and immunoglobulin levels in patients with sickle cell anaemia.

Forty-three patients with homozygous sickle cell disease (haemoglobin SS), 24 heterozygous (AS) subjects and 24 controls (AA) from Sudan were investigated by haemolytic activation for complement function via the classical and the alternative pathways, respectively, and by determination of the plasma levels of C3, C4 and factor B as well as of immunoglobulins IgG, IgA and IgM. The study failed to reveal any direct involvement of the complement system in sickle cell disease and nor was any alteration of the immunoglobulin levels registered as a possible cause of increased susceptibility to infections in patients with homozygous sickle cell anaemia.

Adolescent↗

PubMed1992

Sickle cell anaemia in Sudan: clinical findings, haematological and serum variables.

Ninety homozygous patients with Hb S haemoglobinopathy from Sudan were reported with respect to clinical findings, haematological and serum parameters. For comparison, 27 Hb AS heterozygous subjects and 28 Hb AA controls were investigated also. The patients showed an extreme type of illness presenting with severe clinical signs such as dactylitis, liver enlargement and cardiac complications. There was marked haemolytic anaemia (mean haemoglobin 66 g/l). Some patients also presented with low serum (S)-iron levels, indicating iron deficiency. S-bilirubin, S-ASAT, S-ALAT, S-GT and S-urate were notably raised, most probably as a consequence of haemolysis with liver involvement. The patients had lower S-calcium levels when compared with the AS and AA subjects. This may suggest a possible role of HB S in the production of this feature.

Adolescent↗

PubMed1992

Decreased erythrocyte cholesterol/phospholipid ratio in untreated patients with essential hypertension.

The erythrocyte cholesterol/phospholipid ratio was determined in eight patients with untreated essential hypertension and compared with that of eight age-matched control subjects. The ratio was significantly lower in patients (Wilcoxon's paired rank test; P less than 0.01), and a correlation existed between the ratio and serum cholesterol concentration in patients (r = 0.63) but not in controls (r = 0.02). A reduction in the cholesterol/phospholipid ratio may play a direct role in destabilizing the plasma membrane, which will in turn result in an increase in membrane permeability in essential hypertension.

Adult↗

PubMed1992

Angina pectoris patients with normal coronary angiograms but abnormal thallium perfusion scan exhibit low myocardial and skeletal muscle energy charge.

Seven patients with angina pectoris and 201-thallium scintigraphy indicative of myocardial perfusion defects, but with normal coronary angiograms, were investigated. Metabolic events were studied in biopsies from myocardium and skeletal muscle (m. quadriceps femoris). Profound metabolic derangement was evidenced by a distinctly lowered energy charge in myocardium (0.88 +/- 0.04 in controls vs. 0.48 +/- 0.09 in patients; P less than 0.001) and skeletal muscle (0.92 +/- 0.01 in controls vs. 0.70 +/- 0.09 in patients; P less than 0.01). Accordingly, low values were recorded for ATP in both types of muscle, where ATP was lower than (myocardium) or the same as (skeletal muscle) ADP. The concentration of myocardial lactate was 115 +/- 74 mumol g-1 dry weight and that of skeletal muscle lactate was 11 +/- 3 mumol g-1 dry weight, compared to normal myocardial lactate of 18 +/- 10 mumol g-1 dry weight and normal skeletal muscle lactate of 11 +/- 3 mumol g-1 dry weight. Unprecedentedly low energy charge levels in both cardiac and skeletal muscle biopsies suggest that a systemic metabolic disease is highly probable. An inverse ATP/ADP ratio found in our patients is indicative of an aetiology different from ischaemia, which would not produce this relationship.

Adenosine Diphosphate↗

PubMed1992

Inhibition of Zn(2+)-dependent ATPase in prostasome membrane by nonsaturated, long-chain fatty acids.

Arachidonic and oleic acids, opposite to stearic and palmitic acids, at concentrations near 10(-5) mol/l markedly inhibited Zn(2+)-dependent ATPase in human prostasome membranes. Arachidonic acid was somewhat more potent as inhibitor than oleic acid and the involvement of the metabolites of arachidonic acid cascade was less probable. Deoxycholate, an anionic biological detergent, produced a similar inhibitory effect although at a much higher concentration. The restraining role of nonsaturated, long-chain fatty acids on sperm motility in human semen is discussed in terms of their established inhibitory action on prostasome ATPase systems.

Adenosine Triphosphatases↗

PubMed1992

Central nervous system damage during cardiac surgery assessed by 3 different biochemical markers in cerebrospinal fluid.

Three cerebral biochemical markers, adenylate kinase (AK), neuron-specific enolase (NSE) and protein S-100, were determined in the cerebrospinal fluid (CSF) of male patients 24 h after coronary artery bypass grafting to investigate the extent of possible center nervous system (CNS) damage and relation to the type of oxygenator and the use of an arterial line filter. The patients were randomized into three groups for extracorporeal circulation (ECC); bubble oxygenator without an arterial line filter (Group I, n = 30), bubble oxygenator with a filter (Group II, n = 29) and a flat-sheet membrane oxygenator without a filter (Group III, n = 33). Pathologically high CSF levels of AK and NSE were found 24 h after ECC in respectively 93% and 95% of the patients. All protein S-100 concentrations were within the normal range. Isolated high CSF concentrations of AK, NSE and protein S-100 were observed in group I. Levels of AK and NSE were the lowest in group III, although there was no statistical difference between the groups. In conclusion, our study suggested that CNS damage caused by ECC involved neurons rather than glial cells. AK and NSE in the CSF seemed to be markers of ischaemic neuronal damage. Postoperative levels of biochemical markers in the CSF tended to be the lowest in the flat-sheet membrane oxygenator group.

Adenylyl Cyclases↗

PubMed1991

Regional differences in energy charge of the pregnant human uterus regardless of functional status in comparison with the non-pregnant uterus.

The energy status of the cell is mainly dependent on adenine nucleotides and can be expressed as energy charge (EC). EC is known to be kept at narrow limits near 0.90 under normal conditions in most cells. We recently reported remarkably low EC values in the human uterus under apparent steady-state conditions. The present paper is an extension of previous work. It shows that EC varies in different regions of the uterus in that the isthmic part in pregnant women displays a higher EC than the fundus of the uterus. There were no intergroup differences between non-pregnant and term pregnant women, nor between those who were in active normal labour, dysfunctional labour or those who were not in labour at all. On the other hand, EC in uterine muscle of post-menopausal women showed a significantly lower EC value. Human uterus seems to manage its metabolic requirements under different functional conditions in spite of low ATP and EC values. This suggests that ATP occurs in sufficient amounts to pertinent enzyme reactions, especially ATPases, which means Km values adapted for this unusually low ATP concentration.

Adenosine Triphosphatases↗

PubMed1991

Dopamine and high-dose insulin infusion (glucose-insulin-potassium) after a cardiac operation: effects on myocardial metabolism.

Myocardial insulin resistance, in association with surgical stress, restricts the availability of carbohydrates and increases the load of free fatty acids (FFAs) on the heart. On theoretical grounds adrenergic drugs may be expected to aggravate this situation, whereas the opposite is expected from insulin. The influence of dopamine and a combination of dopamine (7 micrograms/kg body weight/min) and high-dose insulin (7 IU/kg) on myocardial energy metabolism was studied in 19 patients 4 to 6 hours after a coronary operation. Infusion of dopamine (7 micrograms/kg body weight/min) induced metabolic changes that may be unfavorable to the strained myocardium. There was an increase of the myocardial FFA load and a rise in myocardial oxygen expenditure by 60% to 70%. There changes were, however, not matched by an increase in myocardial substrate uptake. "Oxygen wastage" of FFA metabolism at high circulating catecholamine levels is suggested. There were also signs suggesting an amplified systemic trauma response: systemic oxygen consumption increased by 15%, and an increase in the arterial levels of FFAs, glucose, and ketones was observed. Divergent metabolic effects of dopamine and insulin were demonstrated. The most prominent metabolic effects of adding high-dose insulin to dopamine were a marked reduction of arterial FFA levels and a shift toward myocardial carbohydrate utilization at the expense of FFAs. Myocardial uptake of FFAs ceased. Myocardial insulin resistance may thus to a significant extent be overcome by supraphysiological doses of insulin, even during infusion of adrenergic drugs.

Adult↗