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A van Waarde

Publications and source records attributed to A van Waarde.

15 recordsLinked to original sources
PubMed1995

Quantification of an 11C-labelled beta-adrenoceptor ligand, S-(-)CGP 12177, in plasma of humans and rats.

beta-Adrenoceptors in human lungs and heart can be imaged with the radioligand 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3- dihydro-2H-benzimidazol-2-11C-one (CGP 12177, [11C]I). For quantification of receptor density with compartment models by adjustment of rate constants, an 'input function' is required which consists of the integral of the concentration of unmodified ligand in arterial plasma over time. A discrepancy in the literature regarding metabolic stability of [11C]I prompted us to study metabolism in rats by reversed-phase HPLC (RP-HPLC) of trichloroacetic acid extracts of arterial plasma after i.v. injection of [11C]I (> 11.1 TBq/mmol, 11 MBq/kg). Some plasma samples were also directly applied to an internal-surface reversed-phase (ISRP) column. In parallel experiments, tritiated [11C]I was employed and methanol extracts of arterial plasma were analyzed by straight-phase TLC. The three methods were in excellent agreement. Unmodified [11C]I decreased from > 98.5% (3H) or > 99.9% (11C) initially to 57 +/- 7% at 80 min post injection due to formation of two polar metabolites. Using the RP-HPLC method, no metabolism was detectable in humans up to 30 min after injection of [11C]I (1851 MBq). Deproteinization of plasma with acetonitrile resulted in the formation of a radioactive species (artifact) which eluted immediately after the void volume in RP-HPLC and which could be mistakenly interpreted as a metabolite. Plasma protein binding was low (ca. 30%) in both humans and rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1995

Brain tumors: L-[1-C-11]tyrosine PET for visualization and quantification of protein synthesis rate.

PURPOSE: Positron emission tomography (PET) with the amino acid tracer L-[1-C-11]-tyrosine was evaluated in 27 patients with primary and recurrent brain tumors. MATERIALS AND METHODS: Patients underwent either static (n = 14) or dynamic PET (n = 13), with quantification of protein synthesis rate (PSR) and tumor-to-background ratio. Findings were compared with histologic findings. RESULTS: Primary brain tumor was proved in 22 patients histologically, as well as metastatic cancer of unknown origin, primary non-Hodgkin lymphoma, meningioma, atypical infarction, and vasculitis in one patient each. At PET, 20 of 22 primary tumors, the metastasis, and non-Hodgkin lymphoma were correctly depicted. A false-positive finding was obtained with the infarction, and the meningioma and vasculitis were not depicted. The calculated sensitivity was 92%; specificity, 67%; and accuracy, 89%. There were no statistically significant relationships between histologic findings, PSR, and tumor-to-background ratio. CONCLUSION: L-[1-C-11]-tyrosine is a valid tracer for diagnosis of brain tumors and allowed quantification of PSR.

Adult↗
PubMed1995

In vivo protein synthesis rate determination in primary or recurrent brain tumors using L-[1-11C]-tyrosine and PET.

UNLABELLED: The applicability of protein synthesis rate (PSR) determination with L-[1-11C]tyrosine (11C-TYR) and PET was assessed in patients suspected of a primary or recurrent brain tumor. METHODS: Simultaneous to intravenous injection of 265 MBq of 11C-TYR, dynamic PET acquisition was started and continued for 50 min. Arterial samples were taken and analyzed for 11C-TYR and metabolites. Based on this data, a model was proposed and the corresponding PSR calculated. RESULTS: Plasma metabolites were 11CO2, 11C-proteins and 11C-L-DOPA, constituting more than 50% of total plasma radioactivity at 40 min postinjection. Plasma 11CO2 reached a plateau of around 25% of total plasma radioactivity at 20 min postinjection. Plasma 11C-protein was not detected before 10 min postinjection, but increased exponentially afterwards to 20% at 40 min postinjection. Plasma 11C-L-DOPA was the only acid-soluble radioactive metabolite detected and was less than 8% at 40 min postinjection. Using a five-compartment model, it was shown that while the net PSR was dependent on the recycling of amino acids from protein, the amino acid incorporation was not, which was thus used for subsequent analysis. It was found that our curve-fitting results were unreliable due to the exchange of 11C-TYR between plasma and erythrocytes whereas the graphical Patlak-Gjedde analysis is hardly influenced by this transport phenomenon. The average amino acid incorporation rate thus calculated was 0.7 nmole/ml.min for nontumor tissue with a tumor versus nontumor average ratio of 1.7. CONCLUSION: The assessment of the PSR with TYR-PET is valuable and relatively simple to implement clinically.

Adult↗
PubMed1992

Suitability of CGP-12177 and CGP-26505 for quantitative imaging of beta-adrenoceptors.

[3H]CGP-12177, a non-selective beta-adrenoceptor antagonist, and [3H]CGP-26505, a beta 1-selective beta-adrenoceptor antagonist, were intravenously administered to rats. 94-97% of the injected radioactivity disappeared from plasma with t1/2 0.2 and 0.5 min. Total/non-specific binding ratios of 5.4 and 6.9 (CGP-12177) or 2.0 and 2.8 (CGP-26505) were maintained in heart and lung from 10 to 40 min post-injection. Labelled plasma metabolites appeared after greater than 20 min (CGP-12177) or within 2 min (CGP-26505). No metabolites were found in the heart. CGP-12177 binds to blood cells, but CGP-26505 does not. CGP-12177 can be used for PET imaging of total (beta 1 and beta 2) adrenoceptors in the heart and lung of experimental animals, but CGP-26505 is less suitable for in vivo analysis of the beta 1-subpopulation.

Adrenergic beta-Antagonists↗
PubMed1989

Fish muscle energy metabolism measured by in vivo 31P-NMR during anoxia and recovery.

By means of in vivo 31P nuclear magnetic resonance (NMR) we measured energy stores and intracellular pH at 10-min intervals in the myotome of unanesthetized carp and goldfish before, during, and after a period of anoxia (1 h for carp and 4 h for goldfish). The fish were mounted in a modified bioprobe, and their gills were irrigated with a constant flow of aerated or anoxic water. Anoxia caused a steep decline of phosphocreatine and intracellular pH in carp muscle. After the phosphocreatine stores had been exhausted by greater than 85%, [ATP] fell, whereas IMP and phosphodiesters accumulated. In goldfish muscle, initial changes followed the same pattern, but after 20 min a steady state of high-energy phosphates was reached and the development of acidosis was dampened. The resistance of goldfish to anoxia is due to metabolic suppression and a switch from lactate to ethanol and CO2 as the anaerobic end products. In both species, recovery was complete within 3 h. The fast pH recovery seems to be mainly caused by H+ and lactic acid efflux.

Adenosine Triphosphate↗
PubMed1989

31P NMR studies on rejuvenation of outdated red blood cells: complete regeneration of ATP is accompanied by partial Mg-ATP recomplexation.

We used 31P Nuclear Magnetic Resonance (NMR) spectroscopy to investigate whether regeneration of ATP in outdated human blood is accompanied by Mg-ATP recomplexation. We found that the loss of 'total ATP' (i.e. the sum of ATP4- + MG-ATP2-) which occurs during blood storage is completely reversible by treatment of RBC with precursors for purine nucleotide salvage. The magnesium-ATP complex, however, is only partially (70%) recovered due to a continuous decline of cytosolic free Mg2+ with increasing RBC age. Total RBC magnesium, as measured by flame absorption spectroscopy, did not show any significant change under these conditions.

Adenosine Triphosphate↗
PubMed1988

Metabolic and functional consequences of inhibiting adenosine deaminase during renal ischemia in rats.

The concentrations of renal ATP have been measured by 31P-nuclear magnetic resonance (NMR) before, during, and after bilateral renal artery occlusion. Using in vivo NMR, the initial postischemic recovery of ATP increased with the magnitude of the residual nucleotide pool at the end of ischemia. ATP levels after 120 min of reflow correlated with functional recovery at 24 h. In the present study the effect of blocking the degradation of ATP during ischemia upon the postischemic restoration of ATP was investigated. Inhibition of adenosine deaminase by 80% with the tight-binding inhibitor 2'-deoxycoformycin led to a 20% increase in the residual adenine nucleotide pool. This increased the ATP initial recovery after 45 min of ischemia from 52% (in controls) to 62% (in the treated animals), as compared to the basal levels. The inhibition also caused an accelerated postischemic restoration of cellular ATP so that at 120 min it was 83% in treated rats vs. 63% in untreated animals. There was a corresponding improvement in the functional recovery from the insult (increase of 33% in inulin clearance 24 h after the injury). Inhibition of adenosine deaminase during ischemia results in a injury similar to that seen after a shorter period of insult.

Adenosine Deaminase Inhibitors↗
PubMed1987

What is the function of protein carboxyl methylation?

The following functions of protein carboxyl methylation seem to be reasonably well established: Multiple, stoichiometric methylation of chemotactic receptors in bacteria at glutamyl residues serves as one (but not the only) adaptation mechanism of the transduction chain to constant background levels of chemotactic stimuli. Stoichiometric methylation of hormones and hormone carrier proteins plays a role in hormone storage and secretion by the pituitary gland. Substoichiometric methylation at D-aspartyl residues is involved in a repair mechanism of aged proteins. Stoichiometric methylation of calmodulin modulates the sensitivity of calmodulin-dependent processes to calcium. Research of the past 3 years has indicated that in order to demonstrate an involvement of methylation in the coupling of surface receptors to intracellular events three new criteria have to be met: (a) the cell should possess a protein carboxyl methylase with relatively narrow substrate specificity; (b) methylation should take place at L-amino acid residues; (c) the methyl accepting proteins should be methylated in a stoichiometric fashion.

Animals↗
PubMed1984

Transmethylation inhibitors decrease chemotactic sensitivity and delay cell aggregation in Dictyostelium discoideum.

In Dictyostelium discoideum, extracellular cyclic AMP (cAMP) induces chemotaxis and cell aggregation. Suspensions of cAMP-sensitive cells respond to a cAMP pulse with a rapid, transient increase of protein carboxyl methylation. The transmethylation inhibitors cycloleucine, L-homocysteine thiolactone, and coformycin decrease chemotactic sensitivity and delay cell aggregation when administered in concentrations which do not influence cAMP binding to cell surface receptors or the activity of total phosphodiesterase. The ability of the drugs to inhibit chemotaxis could be correlated with their capacity to convert the initial transient positive response of carboxyl methylation to cAMP into a negative one. This suggests that both protein O-methyltransferase and protein methylesterase are activated after stimulation of aggregative cells with cAMP, the net effect being a transient, positive response of methylation. In the presence of a sufficiently large dose of inhibitor, methyltransferase is inhibited, whereas methylesterase activity is much less affected, so that a transient negative response of methylation to cAMP is observed. The slow, positive response of carboxyl methylation to cAMP which occurs ca. 2.5 to 5 min after stimulus administration is not affected by inhibitors of transmethylation. These results suggest that methylation reactions are involved in the chemotactic response of D. discoideum cells to cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Goldfish muscle energy metabolism during electrical stimulation.

Concentrations of key metabolites were determined in goldfish red muscle, while muscle and blood before and after direct electrical stimulation of the myotome (60 pulses/min, amplitude 500 mV, 10 msec pulse duration, during 10 min at 20 degrees C). In white muscle, levels of ATP, aspartate and adenylate energy charge are significantly lowered while those of AMP, IMP, NH3, alpha-ketoglutarate, lactate and malate are increased. In red muscle, the only change induced by stimulation is a 160% increase of the lactate level. In white muscle, IMP-accumulation and ammonia production are equal, suggesting the AMP-deaminase reaction to be the major source of muscular ammonia. Activation of white muscle adenylosuccinate synthetase and adenylosuccinase is suggested by the conversion of aspartate into malate during increased energy demand. There is no evidence of ammonia incorporation into alanine, glutamate or glutamine.

Adenosine Triphosphate↗
PubMed1983

Towards a valid preparation for the in vitro study of energy metabolism in fish muscles.

Slices of lateral red muscle and isolated intact Musculus protractor hyoidei of goldfish were examined for their suitability as model systems for the in vitro study of muscular energy metabolism. Slicing of red muscle causes a strong breakdown of ATP and creatine phosphate and a lowering of the adenylate energy charge. Furthermore, slices do not recover when incubated in an oxygenated balanced salt solution, but show a continuous depletion of direct energy reserves. In contrast with red muscle slices, the Musculus protractor hyoidei can be isolated in an intact state, as shown by constancy of creatine phosphate and adenylate levels and stability of the adenylate energy charge during incubation. Therefore, isolated M. protractor hyoidei seems to be promising as a model system for the in vitro study of muscular energy metabolism.

Adenine Nucleotides↗
PubMed1982

Rapid, transient methylation of four proteins in aggregative amoebae of Dictyostelium discoideum as a response to stimulation with cyclic AMP.

In Dictyostelium discoideum, extracellular cAMP induces chemotaxis and cell aggregation. Suspensions of cAMP-sensitive cells are shown to respond to a 10(-6) M cAMP-pulse with increased methylation of 4 proteins with app. Mr 110000, 46000, 28000 and 16000. The Mr 110000 and 28000 proteins show a triphasic response with maxima 15, 60 and 150-180 s after stimulation. The responses of the Mr 46000 and 16000 proteins are monophasic, maxima being reached 3 and 15 s after stimulation, respectively. Optimal responses of methylation are observed over 10(-7) - 10(-6) M cAMP. The methylation reaction may be involved in the processing of the chemotactic signal.

Cell Aggregation↗
PubMed1982

Nitrogen metabolism in goldfish, Carassius auratus (L.) activities of amidases and amide synthetases in goldfish tissues.

1. Activities of asparagine synthetase, asparaginase, glutamine synthetase and glutaminase have been determined in red muscle, white muscle, brain, kidney, liver and gills of goldfish. 2. Muscle and brain show a capacity for net amide synthesis, while liver and gills are capable of both amide synthesis and degradation. 3. These results are consistent with the hypothesis that amide synthesis and degradation functions as a mechanism controlling tissue ammonia levels and ammonia excretion rates.

Animals↗