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Biomedical subjects

L Davidson

Publications and source records attributed to L Davidson.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1977

L-Asparagainases from Citrobacter freundii.

Three enzymes which catalyze the hydrolysis of L-asparagine have been identified in extracts of Citrobacter freundii. One of these (asparaginase-glutaminase (EC 3.5.1.1) also shows substantial glutaminase activity. This enzyme is extremely labile, is sensitive to inactivation by p-chloromercuribenzoate, and is not protected by dithiothreitol. A second enzyme (asparaginase B) is also sensitive to mercurials but is protected from inactivation by dithiothreitol. This enzyme has a relatively low affinity for L-asparagine (Km = 1.7-10(-3) M). The third enzyme (asparaginase A) is insensitive to inactivation by mercurials, is stable upon long term storage and has a relatively high affinity for L-asparagine (Km = 2.9-10(-5) M). This enzyme has been purified to homogeneity and has a molecular weight of approx. 140 000; the subunit weight being approx. 33 000. The C. freundii asparaginase A produced significant increases in the survival time of C3H/HE mice carrying the 6C3HED lymphoma tumor.

Amino Acids↗
PubMed1977

Purification and properties of L-glutaminase-L-asparaginase from Pseudomonas acidovorans.

An enzyme that catalyzes the hydrolysis of both glutamine and asparagine has been purified to homogeneity from extracts of Pseudomonas acidovorans. The enzyme having a ratio of glutaminase to asparaginase of 1.45:1.0 can be purified by a relatively simple procedure and is stable upon storage. The glutaminase-asparaginase has a relatively high affinity for L-asparagine (Km=1.5 X 10(-5) M) and L-glutamine (Km=2.2 X 10(-5) M) and has a molecular weight of approximately 156,000 the subunit molecular weight being approximately 39,000. Injections of the enzyme produced only slight increases in the survival time of C3H/HE mice carrying the asparagine-requiring 6C2HED Gardner lymphoma and of white Swiss mice carrying the glutamine-requiring Ehrlich lymphoma.

Amidohydrolases↗
PubMed1977

Catecholamine and octopamine concentrations in brains of patients with Reye syndrome.

Dopamine, norepinephrine, and octopamine levels were estimated in regions of brains obtained postmortem from children who died with Reye syndrome and from age-matched controls. Hypothalamic norepinephrine levels were greatly decreased (to 30 percent of control, p less than 0.02) and octopamine levels were increased (to 700 percent of control, p less than 0.01). Levodopa had little effect on the physiologic condition of the patients. However, CNS dopamine and homovanillic concentrations were not elevated by levodopa, indicating that in the present cases levodopa was not metabolized to its catecholamine products. The findings indicate that the encephalopathy of Reye syndrome (as in other types of hepatic coma) may be linked to the presence of false transmitters in the brain and that levodopa is a rational therapy if administered before irreversible CNS changes occur.

Brain Chemistry↗
PubMed1976

The interaction of an anionic photoreactive probe with the anion transport system of the human red blood cell.

N-(4-azido-2-nitrophenyl)-2-aminoethyl[35S]sulfonate is employed as a photoreactive probe for the anion transport system in the human erythrocyte. In the dark and at 37 degrees C the probe penetrates the membrane via a pathway sensitive to specific inhibitors of anion permeability. It reversibly inhibits sulfate and chloride fluxes but the inhibition is reduced by higher concentrations of sulfate. Upon photolysis to produce a reactive nitrene (at 0 degrees C to minimize penetration), the probe inhibition of anion permeability. Under appropriate conditions the degree of inhibition after photoactivation (irreversible) is almost the same as that in the dark (reversible). The binding sites for the radioactive probe are largely found in proteins of 95 000 apparent molecular weight (band 3). After pronase treatment of the labelled cells, most of the probe is found in a 65 000 molecular weight segment derived from the 95 000 molecular weight protein. In this respect the photoreactive probe resembles another potent irreversible inhibitor of anion transport, 4, 4'-diisothiocyano-2, 2' stilbene disulfonate. In fact, most of the binding sites for each probe are common to both. Thus, in the dark, the azido derivative protects the anion system from inhibition by DIDS and substantially reduces the binding of DIDS to band 3 protein. Conversely, pretreatment with DIDS substantially reduces the binding of the photoreactive probe to the same protein. The fact that an apparent substrate for the anion permeation system competes for binding sites with a specific non-penetrating inhibitor of anion permeability suggests that the inhibitory and transport sites may be closely related and implicates the 95 000 molecular weight protein as the element of the anion transport system which contains the substrate binding site.

Biological Transport↗
PubMed1975

Mitosis and early meiosis in Tetrahymena pyriformis and the evolution of mitosis in the phylum Ciliophora.

The micronuclear mitotic spindle of Tetrahymena pyriformis contains several distinctive elements. The 150 or so continuous microtubules (MTs) form a peripheral sheath just inside the inner nuclear membrane while the kinetochore bundles traverse the center of the nucleoplasm. A new set of microtubules, the separation spindle, appears during the 10-fold nuclear elongation which occurs during the late anaphase. Both the separation spindle and peripheral sheath MTs are present in the macronucleus during macronuclear division but there are no definite kinetochore MTs. In the cresent stage of meiotic prophase both peripheral sheath and kinetochore MTs are present in the micronucleus. By using our own, and other workers', data in conjunction with the phylogenetic scheme for the ciliates which has been designed by Corliss (1974, 1975), we have attempted to trace out the evolutionary history of the various elements of the ciliate mitotic spindle. For example, the micronuclear separation spindle can be followed, from its point of origin within the primitive gymnostomes, throughout the phylum. The separation spindle of the macronucleus, by contrast, is lost at the level of the heterotrichs. Similarly, the anaphase breakdown and reconstitution of the nuclear envelope, which occurs in the primitive Loxodes magnus, can be followed up some phyletic branches, such as the heterotrichs, but in the suctorians and some other groups this feature seems to have been lost. Tracing the evolution of the ciliate mitotic spindle is made very difficult both by the incompleteness of the data and by what appear to be a number of cases of secondary reduction and parallel evolution. In general, however, the evolution of mitosis correlates well with the phylogeny of the ciliates constructed by Corliss and we consider this an independent substantiation of the general correctness of his phylogeny.

Biological Evolution↗
PubMed1975

The neurochemistry of Parkinson's disease: effect of L-dopa therapy.

Post-mortem brain material from control and Parkinson's disease patients was examined to elucidate further the neurochemistry of this disease and to determine the mechanism of action of L-dopa as a therapeutic agent. The activities of L-aromatic amino acid decarboxylase (dopa D), tyrosine hydroxylase, monoamine oxidase and catechol-O-methyl transferase were examined; in addition the tissue levels of dopa, 3-O-methyldopa, dopamine (DA) and homovanillic acid (HVA) were determined. In the non-dopa-treated Parkinsonian patients, the greatest decreases were detected for striatal DA and dopa D, with homovanillic acid and tyrosine hydroxylase levels showing a lesser change. The activities of monoamine oxidase and catechol-O-methyl transferase in the striatal nuclei were not different from the controls. The putamen was consistently the most severely affected region. Dopa and 3-O-methyldopa were detectable in all brain areas only in those patients treated with L-dopa shortly before death. The mean concentrations of DA in the striatum of these patients were 1) 9 to 15 times higher than those in non-dopa-treated patients, 2) related to the time before death of the last dose of L-dopa and 3) greater in the striatum of patients clinically classified as "good responders" as compared to "poor responders." Although L-dopa therapy increased homovanillic acid levels in all brain areas, a preferential increase was observed in the striatum. It was concluded that L-dopa's principal therapeutic effects in Parkinson's disease are consistent with its transformation to DA in the striatum.

Aged↗