Inherited phosphofructokinase deficiency associated with hemolysis and exertional myopathy.
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Adolescent↗
Biomedical subjects
G Ronquist
Publications and source records attributed to G Ronquist.
Myocardial inositoltrisphosphate is depressed by dibutyryl cAMP. An experimental study in the isolated working rat heart.
A possible interrelation between IP3 and cAMP was studied in rat myocardium through circumvention of the receptor mediated stimulatory step of adenylyl cyclase by the administration of dibutyryl cAMP (db-cAMP). Changes in IP3 and cyclic nucleotide contents were correlated to changes in contractility after 40 min of beta- and alpha-adrenergic stimulation. Rat hearts (n = 23) were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus as a working preparation. The hearts were allocated to perfusion as control (n = 6); or with phenylephrine (10(-6) mol L-1, n = 6); (-)-isoproterenol (10(-6) mol L-1, n = 6); db-cAMP (2 x 10(-4) mol L-1, n = 5). All hearts were freeze-clamped after 40 min of perfusion. Phenylephrine produced a slow increase in maxdP/dt reaching a maximal value after 10 min (P < 0.05); thereafter it decreased, reaching the control level at 30 min. Isoproterenol perfusion resulted in an early (20 s) increase in maxdP/dt (P < 0.05). Over the next 10s maxdP/dt decreased markedly reaching an inflection point at 30 s. Thereafter only a slow increase during the rest of the perfusion was seen. Dibutyryl cAMP increased maxdP/dt slowly during the whole perfusion period reaching maximum after 40 min. Cyclic-AMP was increased by 21% after 40 min of phenylephrine perfusion while the corresponding increases by isoproterenol and db-cAMP were 131 and 105%, respectively (P < 0.05). Phenylephrine increased IP3 content to the same extent as isoproterenol perfusion (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Carbachol-induced increase in inositol trisphosphate (IP3) content is attenuated by adrenergic stimulation in the isolated working rat heart.
The interrelated responses of concomitant adrenergic and muscarinic receptor stimulation on second messengers and mechanical activity in the isolated perfused working rat heart were studied. The hearts were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus. The hearts were perfused with noradrenaline (10(-6) mol L-1, n = 20), with carbachol (3 x 10(-7) mol L-1, n = 11) or with noradrenaline plus carbachol (n = 20) in the above-mentioned concentrations. The hearts were frozen at 20 s, 30 s and 40 min after addition of noradrenaline and noradrenaline plus carbachol and at 20 s and 40 min after addition of carbachol. Five hearts were freeze-clamped directly after preperfusion and another five hearts after 40 min of perfusion and used as controls. Myocardial cAMP increased at 20 s and 40 min after noradrenaline perfusion. In contrast to this cAMP was unchanged at 20 s and decreased at 40 min after perfusion with noradrenaline plus carbachol. IP3 content increased after 20 s of carbachol- and after 40 min of noradrenaline perfusion (P < 0.05). However, noradrenaline plus carbachol did not induced any significant increase in IP3 content after 20 s and 30 s, but after 40 min a decrease below basal level was found (P < 0.05). Noradrenaline stimulation attenuated muscarinic agonist induced IP3 formation. A reciprocity existed in that noradrenaline induced IP3 formation was attenuated by carbachol. No direct relationship was observed between the IP3 response and contractility, also valid for cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
The value of prostate specific antigen in early diagnosis of prostate cancer: the study of men born in 1913.
PURPOSE: We attempt to elucidate the performance of serum prostate specific antigen (PSA) as a screening test for prostate cancer. MATERIALS AND METHODS: We analyzed sera stored since 1980 in a nested case-control study. RESULTS: The 36 patients with prostate cancer had a markedly greater mean serum PSA level than did 68 subjects without cancer (22.71 versus 2.67, respectively, p < 0.0001). Among the controls 24% had a serum PSA of greater than 4.0 micrograms/l. A serum PSA value exceeding 4.0 micrograms/l. in 1980 was associated with a 20-fold excess risk of cancer between 1981 and 1986, and an 8-fold risk between 1987 and 1991. CONCLUSIONS: Diagnosis of clinically significant prostate cancer can be advanced substantially by serum PSA testing. However, the large number of high serum PSA values in men who remained free of clinical disease emphasizes the need for a more specific screening test.
Aged↗
Multicentre evaluation of a non-wipe system for the rapid determination of total cholesterol in capillary blood, Accutrend Cholesterol on Accutrend GC.
Accutrend Cholesterol, a non-wipe test for the determination of total cholesterol in capillary blood, was evaluated at four clinical centres. Cholesterol determinations with the Accutrend system using capillary blood were compared with results obtained with the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method using the respective capillary sera. Triacylglycerols, uric acid and haematocrit were determined to evaluate potential interference. Imprecision measurements were performed with venous blood. To examine the reproducibility of results from lot to lot, three different lots of test strips were included in these investigations. Results with Accutrend Cholesterol agree with those of the comparison method within systematic differences of +2.5% to -3.2%, depending on the lot. There was no interference by triacylglycerols up to 10.28 mmol/l (900 mg/dl), by uric acid 60 to 400 mumol/l (1 mg/dl to 7 mg/dl), or by haematocrits between 0.35 and 0.54. Impression data show coefficients of variation of generally less than 5%. Thus Accutrend Cholesterol proved to be a reliable system for the determination of total cholesterol.
Blood Chemical Analysis↗
Low energy charge and high adenosine content in smooth muscle of human bladder in comparison with striated muscle.
This study determined the energy charge, adenosine and inosine content of human bladder smooth muscle in comparison with striated muscle of the same individual. Biopsies were obtained from 21 women who were subjected to urethrocystopexy because of urinary stress incontinence. We found that the ATP content of bladder smooth muscle was only about one-eighth of that of striated muscle. The energy charge of bladder smooth muscle was 0.78 +/- 0.13, which is low compared with striated muscle (0.92 +/- 0.02). The adenosine content of bladder smooth muscle was 6.7 times higher than striated muscle and the adenosine/ATP ratio was 1:9 compared with 1:450 for striated muscle. These findings were in accordance with our previous studies on uterine smooth muscle.
Adenosine↗
Promotive effect by prostasomes on normal human spermatozoa exhibiting no forward motility due to buffer washings.
Prostasomes, small corpuscular organelles derived from the prostate gland, were isolated from human seminal plasma by means of ultracentrifugation and Sephadex G 200 chromatography to assess objectively their promotive effect on the motility of buffer-washed normal human spermatozoa exhibiting no forward motility. Prostasomes were efficacious in about 70% of these spermatozoa, and a maximum value was obtained with prostasomes at a concentration corresponding to a protein content of 0.7-0.8 g/l followed by a plateau at higher concentrations. Addition of albumin alone resulted in a similar response although at a somewhat lower level and about 50% of the spermatozoa were rendered motile with a maximum effect of albumin at about 2.5 g/l. Albumin concentrations exceeding 3 g/l were less active. At protein concentrations of 0.25 g/l, prostasomes were superior to albumin in every respect concerning the effects on various sperm movement characteristics. These divergent effects were abolished when comparing prostasomes corresponding to a protein concentration of 0.75 g/l with albumin at 2.3 g/l, i.e. at their respective optimum concentration. Heat treatment and ultrasonication of prostasomes did not affect their motility-promoting properties. Some problem of sperm dysfunction has generally been considered to be a major contributory factor to infertility. By supplementing sperm preparations with postasomes in cases of established male factor, the already poor quality spermatozoa may more frequently be rendered capable of fertilization after insemination.
Humans↗
Enhanced recruitment of motile spermatozoa by prostasome inclusion in swim-up medium.
Prostasomes, which are prostate-derived organelles, were purified from human seminal plasma for inclusion in Earle's balanced salt solution (EBSS) medium with or without human serum albumin. These media were used for swim-up experiments and the subsequent analyses of sperm motility parameters at different incubation times. The yield of motile spermatozoa after swim-up in EBSS medium enriched with boiled prostasomes was increased by 32% compared with EBSS containing albumin. Native prostasomes were less active. Combinations of albumin and either prostasomes or boiled prostasomes significantly increased the recovery of motile spermatozoa and also increased the percentage of spermatozoa displaying progressive motility after 1 h of incubation. Media lacking albumin showed lower values regarding progressive motility after 22 h of incubation. A beneficial effect of prostasomes was noted on lateral head displacement and percentage of hyperactive spermatozoa during the first 6 h of incubation. These results suggest that inclusion of prostasomes, especially boiled prostasomes, in swim-up media may improve the recovery of hyperactive motile spermatozoa for up to 6 h in cases of established male factor infertility, and consequently increase the opportunities for fertilization.
Hot Temperature↗
Direct effect of insulin on 45calcium uptake in human erythrocytes.
OBJECTIVE: High blood pressure is prevalent in obesity and non-insulin dependent diabetes mellitus; both conditions, with insulin resistance and essential hypertension, have been associated with increasing intra-erythrocytic levels of calcium ions. We tested the hypothesis of whether insulin itself might be responsible for the abnormal red cell cytosolic free calcium. DESIGN: The ionic effects of insulin were studied on the kinetics of 45calcium uptake in vitro in normal human erythrocytes. SETTING: The study was performed in the outpatient clinic of a central hospital. SUBJECTS: Sixteen healthy, normotensive individuals with normal body mass index were recruited for the study. MAIN OUTCOME MEASURES: Blood from eight individuals was used for time-dependent studies of 45calcium uptake in erythrocytes and blood from another eight individuals was used for dose-dependent studies of insulin effect. RESULTS: The rate of 45calcium influx in red blood cells has two components, a fast component (0-10 min), which measures the initial rate of 45calcium influx, and a slow component (10-60 min) probably reflecting a relatively large backflux of calcium (calcium efflux), which accordingly determines an apparent low rate of 45calcium influx between 10-60 min. The uptake was linear with time between 10-120 min regardless of insulin being present or not. Insulin at a concentration of 120 mU L-1 significantly decreased the 45calcium uptake in a time-dependent fashion between 10-120 min. The uptake was 508 (+/- 59) at 60 min in the presence of insulin vs. a control value of 529 (+/- 59) pmol mL red blood cells-1 (P < 0.001). The corresponding figures at 120 min were 742 (+/- 109) and 767 (+/- 127), respectively (P = 0.02). Inconsistent results were obtained on 45calcium uptake at 60 min by varying insulin concentrations from 40-640 mU L-1 and a dual effect of insulin on 45calcium uptake could not be excluded, one at a fairly low concentration of insulin (40-120 mU L-1) and another at a high concentration (160-640 mU L-1). CONCLUSION: The data indicate a direct role of insulin in the transport process of calcium into normal human erythrocytes.
Calcium Radioisotopes↗
Dynamic changes of myocardial inositoltrisphosphate and cyclic nucleotides: relationship to contractile response in the perfused working rat heart after adrenergic and muscarinic agonist stimulation.
Initial and late effects by adrenergic and muscarinic agonists on inositol trisphosphate (IP3) and cyclic nucleotide levels were determined and correlated to mechanical response in perfused rat hearts. Forty-three rat hearts were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus as a working preparation. The hearts were perfused as controls (n = 11), or with noradrenaline (10(-6) mol l-1) (n = 21), or with carbachol (3 x 10(-7) mol l-1) (n = 11) added to the perfusion buffer. The hearts were frozen at 20 s, 30 s and 40 min after addition of noradrenaline and at 20 s and 40 min after addition of carbachol, and after 5 and 45 min of control perfusion. cAMP and cGMP were determined by radioligand methods and IP3 by a combined fast performance liquid chromatography (FPLC)-isotachophoretic method. cAMP increased by 36% within 20 s followed by a decrease (22%) during the 10 s following noradrenaline addition. After 40 min cAMP regained its value near that of 20 s. Noradrenaline perfusion did not influence IP3 levels during the first 30 s although the value at 40 min was significantly higher (59%). IP3 increased (42%) after 20 s of carbachol perfusion followed by a 25% decrease at 40 min. Sustained stimulation of beta-receptors (after 40 min in our model) resulted in a repeated increase in cAMP only, without an increase in contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Treatment of renal anaemia with recombinant human erythropoietin results in decreased red cell uptake of 45Ca.
The ability of erythrocytes to undergo deformation may be of importance to erythrocyte survival and to blood flow resistance. In a previous study a decreased deformability was demonstrated in the erythrocytes of uraemic patients treated with recombinant human erythropoietin (rhEPO). Erythrocyte deformability is, at least partly, determined by the intracellular concentration of free calcium ions. Six patients with renal anaemia (initial haemoglobin 95 +/- 11 g/l) were treated with rhEPO. They were examined with regard to certain erythrocyte characteristics before treatment and after reaching a haemoglobin concentration exceeding 120 g/l. A decrease was noted upon treatment in erythrocyte deformability and uptake of 45Ca in vitro. The blood pressure tended to increase. The individual values of the decrease in 45Ca uptake and the increase in systolic blood pressure were positively correlated to each other (r = 0.87; p < 0.05). No correlation was found between changes in erythrocyte deformability and 45Ca uptake. The decrease in 45Ca uptake may be interpreted in two different ways. It could reflect a reduced membrane permeability to calcium ions, or, which is more probable, it could be the end result of an increase in the intracellular metabolic pool of free calcium ions caused by the rhEPO treatment. We, therefore, conclude that rhEPO treatment has certain effects on calcium homeostasis in erythrocytes which may be related to blood pressure regulation.
Adult↗
Parasympathetic muscarinic stimulation limits noradrenaline induced myocardial creatine kinase release: a study in the isolated perfused working rat heart.
It has long been known that high concentrations of catecholamines may induce myocardial damage, and aggravate ischaemic injury. It has also been shown that beta-blockade may protect the myocardium from ischaemic damage. Stimulation of muscarinic receptors modulates beta-adrenergic receptor affinity for isoproterenol and attenuates isoproterenol induced adenylyl cyclase activation. Effects of muscarinic receptor stimulation were therefore investigated in isolated anterogradely perfused rat hearts under different experimental conditions. One group of hearts was perfused with noradrenaline, 10(-6) mol l-1 for 45 min, and another group was perfused with different carbachol concentrations (3 x 10(-7)-10(-5) mol l-1) with or without noradrenaline 10(-6) mol l-1, for 45 min. Release of creatine kinase to the perfusion buffer was taken as a sign of cell damage. Heart rate, left ventricular maxdP/dt and left ventricular pressure were measured throughout the perfusion time by insertion of a 20 gauge cannula through the left ventricular wall near the base. Carbachol (3 x 10(-7) mol l-1) alone induced a decrease of heart rate by 25% and maxdP/dt by 13%. Noradrenaline produced a 20% increase in heart rate, whereas the combination of noradrenaline plus carbachol induced a minor decrease in heart rate. Muscarinic receptor stimulation alone decreased myocardial contractility. However, when combined with noradrenaline no decrease in contractility was seen. Also, the release of creatine kinase to the perfusion buffer containing the combination of carbachol plus noradrenaline was reduced. Thus, muscarinic receptor stimulation protected the myocardium from catecholamine induced damage at concentrations where no change in contractility was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Myocardial metabolism 8 hours after coronary surgery: effects of dopamine.
Myocardial substrate metabolism is abnormal in the early period after cardiac surgery. Myocardial uptake of substrates remains restricted 6 hours postoperatively and cannot match the demand during periods of increased energy requirements. We investigated the relationship between myocardial oxidative rate and substrate uptake in 22 men c. 8 hours after coronary surgery. Myocardial energy demand was raised experimentally by infusing dopamine. The influence of selective beta 1-blockade was analyzed. The uptake of free fatty acids dominated (34.74 +/- 8.83 mmol/min*10(-3) and sufficed to explain the oxygen consumption in basal postoperative conditions (0.468 +/- 0.051 mumol/min) and during amplified energy requirements (0.881 +/- 0.117, r = 0.71). Although the capacity to adjust substrate uptake to energy requirements thus was regained, the uptake of glucose and of lactate (6.14 +/- 13.13 and 2.29 +/- 20.31 mmol/min*10(3) respectively) was marginal, which may be important for ischaemic tolerance. Metoprolol influenced oxygen consumption during amplified adrenergic activity, but did not markedly affect substrates.
Coronary Artery Bypass↗
High adenosine content in human uterine smooth muscle compared with striated skeletal muscle.
We determined the concentrations of adenosine and some of its catabolic products in biopsy specimens from predetermined loci of human myometrium under different functional conditions to compare uterine muscle with rectus abdominis muscle from the same individuals. In order to achieve a good resolution in the separation of nucleosides and purine bases, a preseparation procedure was developed prior to analysis of these compounds on high performance liquid chromatography. Adenosine occurred in a nearly 70-fold higher concentration in smooth uterine muscle in comparison with striated skeletal muscle. Similarly, myometrial inosine and hypoxanthine were 7- and 2.4-times in excess over the rectus muscle, whereas xanthine was scarcely and rather evenly represented in the two types of muscles. The uterine content of adenosine and inosine was distinctly higher in pregnant women compared to non-pregnant ones. A regional difference existed for adenosine, with 3.3 times higher concentration in fundus uteri compared to the isthmic part. A reverse pattern was observed for hypoxanthine and inosine, being 2-3 times more frequent in the isthmic part. The orthophosphate concentration was not stoichiometrically related to the adenosine concentration in a simple way, being 2-3 times lower in uterine muscle compared to the skeletal muscle. A significant correlation existed between uterine contents of AMP and adenosine and similarly, significant inverse correlations were apparent between uterine ATP and ADP contents and energy charge on one hand and adenosine content on the other.
Adenosine↗
Energy economy in the pregnant human uterus at term: studies on arteriovenous differences in metabolites of carbohydrate, fat and nucleotides.
Metabolic regulation was studied in the pregnant human uterus by determining its uptake and release of various substrates, some of which are commonly used as a fuel and some are markers of disturbed energy status in cells. Ten healthy women with normal pregnancy were examined when undergoing elective Caesarean section at term, before onset of labour. Carbohydrate metabolites (glucose, lactate and pyruvate), fat metabolites (free fatty acids (FFA) and glycerol) and nucleotide metabolites (hypoxanthine, xanthine and urate) were determined in arterial (radial artery) and venous (plexus of the uterine and ovarian veins) blood. In addition the arteriovenous difference in each substance across the uterus was calculated. A distinct uptake of glucose was a typical finding in the pregnant uterus as reflected by a positive difference. On the other hand, glycerol and FFA were released from the pregnant uterus. Similarly, a degradation of adenine-containing nucleotides seemed to be continuously ongoing in the pregnant uterus, since oxypurines displayed a negative difference as well.
Adult↗
Dissipation of the calcium gradient in human erythrocytes results in increased heat production.
Heat production rates were measured by a microcalorimetric method in suspended human erythrocytes in the absence and presence of different concentrations of the divalent cationophore A23187. Determinations were carried out during 60 min under static conditions on erythrocytes incubated in various isotonic media at 37 degrees C, pH 7.35. In incubations containing the ionophore, time-power curves showed an early peak followed by a descending slope levelling off at a steady state after 30-60 min. In contrast, the controls lacked the early peak, showing hyperbolic ascending curve profiles before reaching steady state. The appearance of the early peak in the presence of ionophore was dependent upon the composition of the medium, both Mg2+ ions and glucose being decisive. Likewise, dose-response relationships concerning heat production at 60 min depended on the composition of the media. In a basic incubation medium lacking Mg2+ and glucose, no effect was seen on heat production by the ionophore (1-3 mumol/l). Rather modest effects were obtained by the ionophore at 2 and 3 mumol/l when Mg2+ was present. A clear-cut dose-response relationship was observed in a Mg2+ and glucose enriched medium for the ionophore from 1-3 mumol/l. The significant increase in heat production observed at 60 min with 2 mumol/l of A23187 in the Mg2+ and glucose enriched medium was abolished by 1 mmol/l EGTA. Calmidazolium, a calmodulin antagonist, could only marginally reduce the ionophoric effect on heat production. It was concluded that the appearance of the early peak was not the result of an increase in glycolytic rate but rather a consequence of the ionophoric action on the Ca2+ gradient.
Adenosine Triphosphate↗
[Does examination play any role in continuing education? Experiences from clinical chemistry].
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Chemistry, Clinical↗
Characteristics of membrane-bound 5'-nucleotidase on human prostasomes.
Examination of prostasomes, isolated from human seminal plasma, showed that there was very little remaining paranitrophenylphosphatase activity when assayed in the presence of 10 mmol/l of tartrate and 2 mmol/l of levamisole. Under these conditions it was possible to study the prostasome membrane-bound 5'-nucleotidase activity, which was unaffected by these two inhibitors. The activity was considered to be located at the external surface of the prostasome membrane and a 50-60% increase in activity was obtained by the addition of 0.05% Triton X-100. The prostasome membrane-linked 5'-nucleotidase readily hydrolysed 5'-AMP. Two other 5'-nucleoside monophosphates, 5'-IMP and 5'-GMP, were also hydrolysed, but more slowly; 2'- or 3'-AMP were practically not attacked. The prostasome membrane-linked 5'-nucleotidase obeyed Michaelis-Menten kinetics. Apparent Km for 5'-AMP was 11.2 +/- 2.1 mumol/l and Vmax 64.7 +/- 11.4 nmol/mg protein/min. These figures were somewhat changed in presence of 0.05% Triton X-100, the Km value being reduced by 30% and the Vmax value increased by 60%. Adenosine 5' (alpha, beta methylene) diphosphate (100 mumol/l), Ni2+ (10 mmol/l) and concanavalin A (20 micrograms/ml) were all potent inhibitors of the prostasome membrane-linked 5'-nucleotidase.
5'-Nucleotidase↗