PubMed Health⌕ Search

Biomedical subjects

L Davidson

Publications and source records attributed to L Davidson.

At least 55 records · Page 3Linked to original sources
PubMed1982

Epinephrine sulfation in the forearm: arteriovenous differences in free and conjugated catecholamines.

Simultaneously drawn arterial and forearm venous levels of free and sulfate conjugated epinephrine and norepinephrine were measured in 8 subjects in order to study the role of skeletal muscle in catecholamine sulfation. A sensitive radioenzymatic assay was used. The average free epinephrine level was 46% lower in venous than in arterial blood (p less than 0.023) while average sulfated epinephrine level was 37% higher (p less than 0.016). These findings suggest that epinephrine sulfation is occurring in the forearm, most likely in skeletal muscle. The mean venous free norepinephrine level was 21% higher than the mean arterial level (p less than 0.055) presumably reflecting release from sympathetic nerve terminals. No evidence of norepinephrine sulfation or deconjugation in skeletal muscle was found.

Adult↗
PubMed1982

Effects of meclofenamate and captopril on adrenal blood flow: contrasts in conscious rabbits at rest and after hemorrhage.

The role of prostaglandins and angiotensin II or kinins in maintaining adrenal blood flow was studied using the prostaglandin cyclo-oxygenase inhibitor meclofenamate and the kininase inhibitor captopril in resting and hemorrhaged (10 ml/kg) conscious rabbits. Meclofenamate (6 mg/kg intravenously) reduced adrenal blood flow after 3, 15 and 30 minutes by 26, 28 and 17 percent, respectively. Captopril increased adrenal flow by 20 percent, an effect subsequently reversed by meclofenamate. In contrast, hemorrhaged rabbits maintained adrenal blood flow following meclofenamate and captopril despite substantial reductions in renal blood flow with meclofenamate given before and after captopril. It is concluded that (1) adrenal blood flow at rest is modulated by vasodilator prostaglandins and to a lesser extent angiotensin II or bradykinin. (2) The adrenal effects of meclofenamate and captopril are overriden by hemorrhage, perhaps reflecting the need to increase adrenal hormones during hypovolemic stress. (3) The decrease in plasma catecholamines seen with meclofenamate at rest may be due to reduced adrenal blood flow.

Adrenal Glands↗
PubMed1982

Plasma free and sulfate conjugated catecholamine levels during acute physiological stimulation in man.

The responses of plasma free and sulfate-conjugated catecholamines to acute physiological stimulation was examined in normal male subjects. Catecholamines were measured with a sensitive radioenzymatic assay incorporating simultaneous hydrolysis of sulfate conjugates and O-methylation of free norepinephrine and epinephrine. Following 20 minutes recumbency after venepuncture 30 +/- 3% of norepinephrine and 16 +/- 5% of epinephrine was in thr free form. Free catecholamines generally increased during standing, cold immersion and isometric handgrip, but sulfates did not change. Bicycle ergometry markedly increased free catecholamines which rapidly returned to basal levels at the end of exercise. In contrast, sulfated norepinephrine decreased substantially with exercise in all subjects but returned to basal levels 3 minutes after stopping exercise. Epinephrine sulfate varied considerably between subjects but showed a similar, although smaller, fall with exercise. Thus, during physiological stimulation, which caused increases in free norepinephrine and epinephrine levels in plasma, the only consistent change in sulfated catecholamines was a marked fall in norepinephrine sulfate after bicycle exercise. This may indicate saturation of sulfotransferase activity, substrate inhibition or impaired tissue conjugation.

Adult↗
PubMed1982

Effects of meclofenamate and captopril on renal and other regional vascular beds after mild haemorrhage in conscious rabbits.

1. The role of prostaglandins and angiotensin II in blood flow regulation was studied in conscious rabbits subjected to mild haemorrhage. 2. Haemorrhage caused a 13% fall in arterial pressure and a 21% fall in cardiac output, responses which were unchanged by sodium meclofenamate, an inhibitor of prostaglandin synthesis, or captopril, an inhibitor of the angiotensin converting enzyme. 3. Haemorrhage doubled plasma adrenaline and noradrenaline levels. Plasma renin activity trebled after haemorrhage and was further elevated by captopril. 4. Renal blood flow was maintained after haemorrhage alone. Meclofenamate given immediately after haemorrhage caused a 31% fall in renal blood flow. Captopril given immediately after haemorrhage caused renal vasodilation, but when given after meclofenamate augmented renal vasoconstriction. 5. Splenic vasoconstriction was seen after haemorrhage and meclofenamate, and subsequently was augmented by captopril. 6. Results suggest that prostaglandins variably modulate regional blood flow in conscious rabbits subjected to mild haemorrhage. Enhanced sympatho-adrenal activity increases renovascular and splenic dependence on vasodilator prostaglandins, but not that of coronary, cerebral, hepatic or adrenal circulations. Renal and splenic vasoconstriction seen with meclofenamate are not due to circulating angiotensin II.

Animals↗
PubMed1981

Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome.

Different brain regions were removed post mortem from three patients with the Lesch-Nyhan syndrome and were examined for alterations in hypoxanthine-guanine phosphoribosyl transferase (HGPRT), adenine phosphoribosyl transferase, and biochemical indexes of norepinephrine, dopamine, serotonin, gamma-aminobutyric acid (GABA), and acetylcholine neuron function, as compared with age-matched controls. The level of HGPRT activity in the material from patients with the Lesch-Nyhan syndrome was less than 1 per cent of control levels, whereas adenyl phosphoribosyl transferase was not significantly altered. All biochemical aspects of the function of dopamine-neuron terminals in the striatum (except dihydroxyphenylacetic acid levels) were decreased to 10 to 30 per cent of the control values. Serotonin and 5-hydroxyindoleacetic acid levels were increased, striatal choline acetyltransferase levels were low, and striatal glutamic acid decarboxylase and guanylate cyclase activities were unaltered. The disruption of the balance between the functions of GABA, dopamine, and acetylcholine neurons in the extrapyramidal system probably accounts for some of the symptoms observed in the Lesch-Nyhan syndrome (e.g., choreoathetosis).

Acetylcholine↗
PubMed1981

Effect of beta-adrenergic receptor blockade with propranolol on the response of plasma catecholamines and renin activity to upright tilting in normal subjects.

1 Relationship between plasma catecholamines (measured as noradrenaline and adrenaline) and plasma renin activity (PRA) were examined at rest and during passive head-up tilting for 30 min in nine normal subjects, before and after treatment with propranolol 160 mg daily for 7 days. 2 Noradrenaline (NA) and adrenaline (A) increased substantially after tilting for 15 min. There were no changes in PRA. After 30 min tilting, NA remained elevated, whereas A had returned to resting levels. A significant increase in PRA was apparent at 30 min. Pulse rate and diastolic blood pressure increased progressively during tilting. Systolic pressure did not change. 3 Treatment with propranolol reduced pulse rate and systolic blood pressure at rest and during tilting. Resting catecholamine concentrations and the response of NA to tilting were unaffected. In contrast, treatment prolonged the A response leading to significantly higher levels after 30 min tilting. Propranolol reduced PRA in six of the nine subjects and prevented the increase with tilting observed before treatment.

Adult↗
PubMed1980

Kinetics of L-DOPA metabolism in the caudate nucleus of cats with ventrotegmental lesions.

Sixteen days after a unilateral lesion of the ventromedial tegmentum (VMT) of the midbrain, adult cats received an intravenous dose of L-DOPA (20 mg/kg), and the caudate nucleus from each hemisphere was removed at various time intervals thereafter. In the caudate nucleus contralateral, to the VMT lesions, DA levels reached 200% of control values within 15 min, and maintained this elevation for at least 2 hours. DA levels in the caudate nucleus ipsilateral to the VMT lesion were much lower than contralateral values; however, they were much higher than those of non-DOPA treated animals with comparable lesions. DA levels in the caudate nucleus of the lesioned hemisphere were directly related to the remaining DOPA decarboxylase activity. The striatal serotonin concentrations were unchanged after L-DOPA, but an increase in 5-hydroxyindoleacetic acid levels was observed. From these results, we conclude that, (i) in cats with nigrostriatal tract lesions after low doses of L-DOPA comparable to those given to patients with Parkinson's disease, the bulk of the newly formed DA in the caudate nucleus is contained in nigrostriatal neurons, and (ii) there exists an inverse relationship between the ability of the caudate to synthesize DA and the severity of the nigrostriatal tract lesion.

Animals↗
PubMed1979

[3H]GABA binding in brains from Huntington's chorea patients: altered regulation by phospholipids?

Binding sites for tritum-labeled gamma-aminobutyric acid (GABA) in cerebellar cortex of Huntington's chorea patients have an increased affinity but unaltered maximum capacity as compared to binding sites in tissue from control patients. A similar binding pattern is produced in control membranes by treatment with Triton X-100, phospholipase C, or glycerophosphoethanolamine. Thus, it is likely that phospholipids or their metabolites regulate the accessibility of the GABA binding site and that this regulation is abnormal in Huntington's chorea.

Cerebellar Cortex↗
PubMed1979

Sodium-independent, high-affinity binding of [3H]gamma-aminobutyric acid in human neurological disorders.

With respect to [3H]GABA-binding in material prepared from human post-mortem brain, the following observations have been made: (1) The [3H]GABA binding site in the cerebellum has the pharmacological characteristics of the physiological GABA-receptor observed in other species. Together with the post-mortem stability exhibited for [3H]GABA-binding, this provides an approach for determining the functional state of the GABA-receptor in various disease states; (2) In Parkinson's disease [3H]GABA-binding in the substantia nigra is significantly decreased whereas that in the putamen and caudate nucleus is unaltered. The former finding likely indicates that GABA binding sites (receptors) occur on nigral dopaminergic cell bodies and/or dendrites. The latter finding may signify that relatively few of the striatal [3H]GABA binding sites occur on dopaminergic nerve terminals in the human caudate or putamen; (3) In Huntington's disease [3H]GABA binding was decreased in the caudate nucleus and putamen, in parallel wih the massive cell loss and gliosis observed in this condition. Membranes prepared from cerebellar tissue of these patients possessed an increased affinity for [3H]GABA-binding; (4) Pre-treatment of cerebellar membranes from control brains with Triton-X-100 (0.02%) or phospholipase-C (0.001 units) results in kinetic changes very similar to those observed in Huntington's brains. In contrast, such treatment was virtually without effect on the IC50 or KD for [3H]GABA on cerebellar membranes prepared from Huntington's brains; (5) These results imply that a phospholipid, possibly related to phosphoglycerolethanolamine, is altered in the membrranes of Huntington's patients and that this phospholipid normally has a role in controlling accessibility to the GABA-receptor.

Binding, Competitive↗
PubMed1979

Tumor inhibitory and non-tumor inhibitory L-asparaginases from Pseudomonas geniculata.

Two enzymes that catalyze the hydrolysis of l-asparagine have been isolated from extracts of Pseudomonas geniculata. After initial salt fractionation, the enzymes were separated by chromatography on diethylaminoethyl-Sephadex and purified to homogeneity by gel filtration, ion-exchange chromatography, and preparative polyacrylamide electrophoresis. The enzymes differ markedly in physicochemical properties. One enzyme, termed asparaginase A, has a molecular weight of approximately 96,000 whereas the other, termed asparaginase AG, has a molecular weight of approximately 135,000. Both enzymes are tetrameric. The asparaginase A shows activity only with l-asparagine as substrate, whereas the asparaginase AG hydrolyzes l-asparagine and l-glutamine at approximately equal rates and it is also active with d-asparagine and d-glutamine as substrates. The asparaginase A was found to be devoid of antitumor activity in mice, whereas the asparaginase AG was effective in increasing the mean survival times of both C3H mice carrying the asparagine-requiring Gardner 6C3HED tumor line and Swiss mice bearing the glutamine-requiring Ehrlich ascites tumor line. These differences in antitumor activity were related to differences in the K(m) values for l-asparagine for the two enzymes. The asparaginase A has a K(m) value of 1 x 10(-3) M for this substrate whereas the corresponding value for the AG enzyme is 1.5 x 10(-5) M. Thus the concentration of asparagine necessary for maximal activity of the asparaginase A is very high compared with that of the normal plasma level of asparagine, which is approximately 50 muM.

Animals↗
PubMed1978

American Burkitt's lymphoma-hand-mirror variant. A detailed investigation of cytologic, ultrastructural, and immunologic features.

Previous studies of patients with lymphoid malignancies have suggested a relationship between survival and the presence of more than 40% hard-mirror cells in the bone marrow. This report represents the first detailed study of a patient with American Burkitt's lymphoma with numerous hand-mirror cells in the bone marrow during the course of the disease. The Burkitt cells were atypical because of their hand-mirror configuration in the bone marrow, the presence of cytoplasmic glycogen, the finding of an IgG surface marker, and a strongly positive acid phosphatase staining reaction. The presence of increased numbers of hand-mirror forms in the bone marrow during the course of the patient's illness may have clinical significance, because they were replaced by non-hand-mirror Burkitt cells in the terminal phase. More reports and investigations of patients with large numbers of hand-mirror forms in the bone marrow are needed to elucidate the full significance of this unusual cellular phenomenon.

Adult↗