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J Bergman

Publications and source records attributed to J Bergman.

At least 109 records · Page 6Linked to original sources
PubMed1995

Differential effects of dopamine D1 and D2 receptor agonists on schedule-controlled behavior of squirrel monkeys.

The effects of dopamine agonists differing in affinity and selectivity at D1 and D2 types of dopamine receptors were compared in squirrel monkeys responding under two different schedules of reinforcement: a fixed-interval (FI) schedule of stimulus-shock termination and a fixed-ratio (FR) schedule of food presentation. Dopamine D1 family agonists included dihydrexidine, SKF 81297, SKF 82958, R-6-Br-APB, SKF 83189, SKF 77434, SKF 75670 and R- and R, S-SKF 38393. Dopamine D2 agonists included (+)-PHNO, quinpirole and N-0434; nonselective DA agonists included R(-)-apomorphine and CY 208-243. The behavioral effects of D1 agonists differed qualitatively from those of D2 and nonselective DA agonists. D1 agonists produced dose-related decreases in both FI and FR responding, with comparable doses being effective under the two schedules. The rank order of potency for the rate-decreasing effects of these drugs was R(+)-6-Br-APB > SKF 75670 > SKF 82958 > R-SKF 38393 > SKF 81297 > SKF 77434 > SKF 83189 > dihydrexidine > R, S-SKF 38393. In contrast, D2 and nonselective DA agonists produced significant increases in rates of FI responding at doses that reduced FR response rates. The rank order of potency for the rate-increasing effects of these drugs under the FI schedule was (+)-PHNO > N-0434 > R-apomorphine > CY 208-243 > quinpirole.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

FDG-PET in early infancy: simplified quantification methods to measure cerebral glucose utilization.

UNLABELLED: For further insight into the physiology and pathogenesis of the developing brain, quantification of the cerebral glucose metabolism is needed. Arterial blood sampling or sampling of great volumes of blood is not justified for the purpose of PET studies in children. Therefore, we have developed simplified PET approaches to analyze brain FDG examinations during infancy. METHODS: The study consisted of 18 FDG-PET examinations chosen from our research protocols concerning hypoxicischemic encephalopathy and severe neonatal hypoglycemia. The input function for graphical analysis according to Patlak was derived in two ways: (1) a combined time-activity curve derived from the left ventricular activity concentration (first 7-17 min of the study) and radioactivity concentration in venous whole-blood samples and; (2) activity concentration measured in whole-blood venous blood samples (arterial plasma in one case). As an alternative for semiquantitation, the standardized uptake values (SUV) were calculated and correlated to local cerebral metabolic rates for glucose (LCMRGlc). RESULTS: The influx rate constants (Ki) and LCMRGlc values obtained using the combined curve versus venous curve did not differ statistically (p > 0.05). There was a good correlation between the SUV and LCMRGlc values (r = 0.83, p < 0.001). CONCLUSION: Local cerebral metabolic rates for glucose can be accurately calculated by using the combined curve (left ventricular activity concentration during first 5 min of the study and 2-3 venous whole-blood samples at the end of the study) for even the smallest pediatric patients. When blood samples cannot be obtained, SUV values provide an alternative for estimation of the cerebral glucose uptake and interindividual comparison of the patients.

Brain↗
PubMed1994

Animal transport.

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Animal Welfare↗
PubMed1994

Catalepsy-associated behavior induced by dopamine D1 receptor antagonists and partial dopamine D1 receptor agonists in squirrel monkeys.

Observational procedures were used to compare the behavioral effects of dopamine D1 receptor antagonists and partial dopamine D1 receptor agonists in squirrel monkeys. The dopamine D1 receptor antagonists SCH 39166 ((-)-trans-6-7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N- methyl-5H-benzo(d)naphtho-(2,1-b)azepine) and BW 737C89 ([S]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7- hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) produced dose-related increases in the duration of static and unusual postures, indicative of catalepsy. R-SKF 38393 (R(+)-7,8- dihydroxy-1-phenyl-2,3,4,5-tetrahydro-[1H]-3-benzazepine) and SKF 75670 (7,8-dihydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-[1H]-3- benzazepine), which are considered partial dopamine D1 receptor agonists, also consistently produced dose-related increases in catalepsy-associated behavior and had effects comparable in magnitude to those of dopamine D1 receptor antagonists. In contrast, the higher efficacy D1 agonists SKF 81297 (6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-[1H]-3- benzazepine) and SKF 82958 (6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-3-allyl-[1H]-3- benzazepine) did not produce catalepsy-associated behavior at any dose tested. The results indicate that dopamine D1 agonists differ with respect to cataleptogenic activity, possibly reflecting differences in intrinsic activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

In vivo effects of insulin on tumor and skeletal muscle glucose metabolism in patients with lymphoma.

BACKGROUND: The anabolic properties of insulin have been suggested for use to reverse malnutrition associated with cancer. The host and tumor sensitivities to insulin are critical for such treatments, which aim to improve patient nutrition. The authors studied insulin effects on tumor and skeletal muscle metabolism with 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET). METHODS: Six patients with lymphoma twice underwent [18F]FDG-PET imaging: once after fasting overnight and once during euglycemic hyperinsulinemic clamp. The dynamic uptake of the glucose analogue [18F]FDG was measured in diseased nodes and upper arm skeletal muscle in both metabolic states. The [18F]FDG uptake in muscle and the whole body glucose use during euglycemic hyperinsulinemic clamp were compared with those of weight-matched healthy subjects studied under similar circumstances. RESULTS: In lymphomatous tissue, [18F]FDG uptake rates were similar in overnight fasting and euglycemic hyperinsulinemic clamp (38 +/- 10 versus 41 +/- 9 mumol/100 g/minute, not significant), whereas glucose uptake in skeletal muscle was increased by insulin (1.7 +/- 0.2 versus 3.8 +/- 0.5 mumol/100 g/minute, P = 0.012). Both basal (2.3 +/- 0.2 mumol/100 g/minute, P = 0.061) and insulin-stimulated (8.5 +/- 1.9 mumol/100 g/minute, P = 0.055) skeletal arm muscle glucose uptake rates were higher in control subjects than in patients. Whole body glucose use was 55% lower in patients than in control subjects (17 +/- 3 mumol/kg/minute versus 38 +/- 3 mumol/kg/minute, P = 0.002), consistent with insulin resistance in cancer. CONCLUSIONS: We found that insulin does not induce major changes in glucose uptake of lymphomatous tissue. Although insulin sensitivity of skeletal muscle was also reduced in patients with lymphoma, the net insulin effect may counteract imbalance between glucose uptake of tumor and muscle, offering a potential means to circumvent at least some metabolic abnormalities found in cancer.

Adult↗
PubMed1994

The interaction of ellipticine derivatives with nucleic acids studied by optical and 1H-nmr spectroscopy: effect of size of the heterocyclic ring system.

The DNA interaction of derivatives of ellipticine with heterocyclic ring systems with three, four, or five rings and a dimethylaminoethyl side chain was studied. Optical spectroscopy of drug complexes with calf thymus DNA, poly[(dA-dT).(dA-dT)], or poly[(dG-dC).(dG-dC)] showed a 10 nm bathochromic shift of the light absorption bands of the pentacyclic and tetracyclic compounds upon binding to the nucleic acids, which indicates binding by intercalation. For the tricyclic compound a smaller shift of 1-3 nm was observed upon binding to the nucleic acids. Flow linear dichroism studies show that the geometry of all complexes is consistent with intercalation of the ring system, except for the DNA and poly[(dG-dC).(dG-dC)] complexes of the tricyclic compound, where the average angle between the drug molecular plane and the DNA helix axis was found to be 65 degrees. One-dimensional 1H-nmr spectroscopy was used to study complexes between d(CGCGATCGCG)2 and the tricyclic and pentacyclic compounds. The results on the pentacyclic compound show nonselective broadening due to intermediate chemical exchange of most oligonucleotide resonances upon drug binding. The imino proton resonances are in slow chemical exchange, and new resonances with upfield shifts approaching 1 ppm appear upon drug binding, which supports intercalative binding of the pentacyclic compound. The results on the tricyclic compound show more rapid binding kinetics and very selective broadening of resonances. The data suggest that the tricyclic compound is in an equilibrium between intercalation and minor groove binding, with a preference to bind close to the AT base pairs with the side chain residing in the minor groove.

Animals↗
PubMed1994

Observational studies of dopamine D1 and D2 agonists in squirrel monkeys.

The behavioral effects of selective D1 and D2, nonselective, and indirectly acting dopamine agonists were compared in squirrel monkeys using continuous observation procedures. D1 agonists including SKF 81297, SKF 82958, and R(+)-6-Br-APB produced dose-dependent increases in the frequencies of stationary postures and head movements and had little or no effect on either huddling or scratching. In contrast, SKF 75670 and R-SKF 38393, which are considered to be D1 partial agonists, had effects comparable to those of the D1 antagonist SCH 39166. That is, the D1 partial agonists increased the duration of huddling without greatly altering the frequencies of stationary postures, head movements, or scratching. Unlike the D1 agonists, the D2 agonists (+)-PHNO, quinpirole, and bromocriptine increased the frequency of scratching, but did not consistently alter other observable behaviors. The indirect dopamine agonists cocaine, GBR 12909, and d-amphetamine and the nonselective D1/D2 agonist CY 208-243, but not (-)apomorphine, had effects comparable to those of D1 agonists such as SKF 81297. That is, each of these drugs increased the frequencies of stationary postures and head movements with little or no effect on scratching or huddling. Additionally, effects of the D1 agonist SKF 82958 and the indirect dopamine agonist cocaine were surmountably antagonized by the D1 antagonist SCH 39166. The present results show that: 1) behavioral effects of D1 and D2 agonists in monkeys are qualitatively different; 2) D1 agonists presumed to differ in intrinsic activity have dissimilar effects; and 3) effects of indirect dopamine agonists are comparable to those of D1 agonists with presumably high intrinsic activity.

Animals↗
PubMed1994

Myocardial viability: fluorine-18-deoxyglucose positron emission tomography in prediction of wall motion recovery after revascularization.

To assess the value of positron emission tomography (PET) imaging with fluorine-18-deoxyglucose ([18F]FDG) in predicting cardiac wall motion recovery after revascularization, 48 consecutive patients with previous myocardial infarction were studied. The normalized [18F]FDG uptake at rest was assessed semiquantitatively and compared to perfusion at rest as studied by SPECT imaging. Wall motion was analyzed with echocardiography before and after revascularization. Wall motion recovery occurred in 27 (30%) of the revascularized 90 dysfunctional segments. Preserved [18F]FDG uptake (mean +/- 2 SD) was commonly found in dysfunctional segments, but only 54% of these segments recovered after revascularization. Subnormal [18F]FDG uptake identified accurately the segments with no potential to recover (predictive value 100%). By using an optimized threshold value for normalized [18F]FDG uptake, the sensitivity of 85% and specificity of 84% to predict functional recovery were reached simultaneously. However, in the segments with moderately or severely reduced perfusion at rest, the diagnostic accuracy of [18F]FDG uptake for viability was 100%. The results of this study show that the presence of viable tissue indicated by preserved [18F]FDG uptake does not inevitably imply functional recovery after revascularization. However, acceptable diagnostic accuracy for viability might be reached by [18F]FDG alone, providing that appropriate uptake limits are used. The combined evaluation of [18F]FDG uptake and perfusion enables precise assessment of myocardial viability.

Angioplasty, Balloon, Coronary↗
PubMed1994

Synthesis of fluorescent derivatives of 7-methylguanine through reaction with 2-aryl-substituted malondialdehydes: analysis by HPLC with fluorescence detection.

Fluorescent derivatives of 7-methylguanine were prepared through reaction with 2-aryl-substituted-malondialdehydes and analysed by reversed-phase HPLC with fluorescence detection. Reaction of carbons 1 and 3 of the malondialdehyde molecule at the N1 and N2 positions of 7-methylguanine yielded fluorescent tricyclic structures. Two novel fluorescent derivatives of 7-MeG were obtained, namely, 7-(3,4-dimethoxyphenyl)-10-oxo-1-methyl-9,10-dihydropyrimido[1,2- alpha]purine (yield 15-34%) and 7-(1-naphthyl)-10-oxo-1-methyl-9,10- dihydropyrimido[1,2-alpha]purine (yield 56-70%) after reaction with 3,4-dimethoxyphenylmalondialdehyde and 1-naphthylmalondialdehyde, respectively which were characterized by IR, NMR, MS and UV and fluorescence spectroscopy. The fluorescence intensity of the derivatives was found to be 10-20-fold higher than the intrinsic fluorescence of 7-methylguanine. Concentration versus fluorescence intensity curves exhibit linearity in the picomole to nanomole range. The 2-aryl-substituted malondialdehydes were used to analyse the concentration of 7-methylguanine in neutral hydrolysates obtained from calf thymus DNA samples alkylated with dimethyl sulfate. The results obtained indicate their potential as reagents for the analysis of alkylated guanines in biological samples. Molecular modeling calculations were carried out to generate lowest energy spatial configurations. The results obtained indicated that the aryl-substituents on the malondialdehyde moiety do not lie in the same plane as the tricyclic moiety of the fluorescent derivatives with implications for their fluorescence properties.

Chromatography, High Pressure Liquid↗
PubMed1994

Amphetamine-like effect of l-deprenyl (selegiline) in drug discrimination studies.

l-Deprenyl has dose-dependent amphetamine- and methamphetamine-like discriminative stimulus properties in rats and monkeys. However, these actions occur only at doses that are well above the clinically relevant dose range for l-deprenyl and are likely to reflect its metabolic conversion to amphetamine products. In view of its weak potency for producing amphetamine-like effects and their slow onset, it may not be surprising that l-deprenyl does not appear to have amphetamine-like abuse potential and has been used therapeutically in the treatment of Parkinson syndrome for more than 20 years with no reported instances of abuse.

Amphetamine↗
PubMed1994

Different alterations in the insulin-stimulated glucose uptake in the athlete's heart and skeletal muscle.

Physical training increases skeletal muscle insulin sensitivity. Since training also causes functional and structural changes in the myocardium, we compared glucose uptake rates in the heart and skeletal muscles of trained and untrained individuals. Seven male endurance athletes (VO2max 72 +/- 2 ml/kg/min) and seven sedentary subjects matched for characteristics other than VO2max (43 +/- 2 ml/kg/min) were studied. Whole body glucose uptake was determined with a 2-h euglycemic hyperinsulinemic clamp, and regional glucose uptake in femoral and arm muscles, and myocardium using 18F-fluoro-2-deoxy-D-glucose and positron emission tomography. Glucose uptake in the athletes was increased by 68% in whole body (P < 0.0001), by 99% in the femoral muscles (P < 0.01), and by 62% in arm muscles (P = 0.06), but it was decreased by 33% in the heart muscle (P < 0.05) as compared with the sedentary subjects. The total glucose uptake rate in the heart was similar in the athletes and control subjects. Left ventricular mass in the athletes was 79% greater (P < 0.001) and the meridional wall stress smaller (P < 0.001) as estimated by echocardiography. VO2max correlated directly with left ventricular mass (r = 0.87, P < 0.001) and inversely with left ventricular wall stress (r = -0.86, P < 0.001). Myocardial glucose uptake correlated directly with the rate-pressure product (r = 0.75, P < 0.02) and inversely with left ventricular mass (r = -0.60, P < 0.05) or with the whole body glucose disposal (r = -0.68, P < 0.01). Thus, in athletes, (a) insulin-stimulated glucose uptake is enhanced in the whole body and skeletal muscles, (b) whereas myocardial glucose uptake per muscle mass is reduced possibly due to decreased wall stress and energy requirements or the use of alternative fuels, or both.

Adult↗
PubMed1994

Enhancement of myocardial [fluorine-18]fluorodeoxyglucose uptake by a nicotinic acid derivative.

UNLABELLED: Recently, the euglycemic hyperinsulinemic clamp technique was shown to give excellent image quality during metabolic steady-state conditions. Acipimox is a new potent nicotinic acid derivative that rapidly reduces serum free fatty acid (FFA) levels by inhibiting lipolysis in peripheral tissue. METHODS: To compare the effects of acipimox administration and insulin clamp on [18F]fluorodeoxyglucose ([18F]FDG) uptake and myocardial glucose utilization, five nondiabetic and seven type II diabetic patients who had had previous myocardial infarctions were studied twice: once during a clamp study and once after the administration of acipimox (2 x 250 mg orally). All patients also underwent resting SPECT perfusion imaging prior to PET scans. RESULTS: The patients tolerated acipimox well. Although fasting plasma glucose levels were higher in diabetic patients (9.2 +/- 3.4 versus 5.5 +/- 0.3 mM, p = 0.03), they were decreased both during clamping and after acipimox; during imaging, no significant differences between the groups and approaches were detected. By visual analysis, the image quality and myocardial [18F]FDG uptake patterns were similar during clamping and after acipimox. Compared with the relative [18F]FDG uptake values obtained during clamping, acipimox yielded similar results in normal, mismatch and scar segments (r = 0.88, p = 0.0001). Similar rMGU values were also obtained during both approaches. CONCLUSION: Thus, PET imaging with [18F]FDG after the administration of acipimox is a simple and feasible method for clinical viability studies both in nondiabetic and diabetic patients. It results in excellent image quality and gives rMGU levels similar to the insulin clamp technique.

Adult↗
PubMed1993

PET study on striatal dopamine D2 receptor changes during the progression of early Parkinson's disease.

[11C]Raclopride uptake to dopamine D2 receptors was investigated with positron emission tomography (PET) in patients with early Parkinson's disease at the time of the diagnosis and after a half-year interval. During this progressive period of the disease, the patients received no antiparkinsonian medication. The upregulation of striatal D2 receptors, which was seen in all patients already at the time of the diagnosis, persisted. Although the patients initially showed unilateral disease, they had developed bilateral symptoms by the time of the second PET scan, but the disease was still asymmetric. The present results show that the relative increase in [11C]raclopride uptake in the striatum contralateral to the symptoms as compared with the opposite striatum will be preserved even during the progression of the disease, provided that the symptoms show clear-cut asymmetry.

Adult↗
PubMed1993

Repeated fluorodeoxyglucose positron emission tomography of the brain in infants with suspected hypoxic-ischaemic brain injury.

Positron emission tomography (PET) permits the study of cerebral metabolism in vivo. We performed repeated PET studies with fluorine-18 fluorodeoxyglucose (FDG) as a tracer to measure cerebral glucose metabolism for estimation of neurological prognosis in infants with suspected hypoxic-ischaemic brain injury. Fourteen infants (gestational age 35.3 +/- 4.67 weeks) were examined during the neonatal period (at age 38.4 +/- 2.7 weeks) and again at the age of 3.5 +/- 0.7 months; one further infant was studied only once at the age of 2.5 months. All children also underwent ultrasound examinations. Electroencephalography and computed tomography or magnetic resonance imaging were performed according to their clinical condition and their neurological development has been followed. FDG accumulated most actively in the subcortical areas (thalami, brainstem and cerebellum) and the sensorimotor cortex during the neonatal period. The repeated PET study showed that the uptake of FDG was markedly high and increased in all brain sections of infants with normal development (n = 11), whereas those with delayed development (n = 4) had significantly lower values (P < or = 0.005).

Brain Ischemia↗