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Biomedical subjects

W Lovenberg

Publications and source records attributed to W Lovenberg.

At least 145 records · Page 8Linked to original sources

Rubredoxin.

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Amino Acid Sequence↗

Heat-stable low molecular weight form of phosphodiesterases from bovine pineal gland.

The 105,000 X g supernatant fraction of bovine pineal gland contains a phosphodiesterase activity that hydrolyzes both cyclic AMP and cyclic GMP. The rate of hydrolysis is 4-5 times greater with cyclic GMP as substrate than with cyclic AMP. Chromatography of supernatant fraction on Sephadex G-150 resolves phosphodiesterase activity into two fractions designated PDE I and PDE II. These are distinguishable on the basis of their molecular size, substrate specificity, and kinetic parameters. PDE I hydrolyzes cyclic GMP at a faster rate than cyclic AMP and has a molecular weight of 163,000. PDE II appears to be a smaller protein with a molecular weight of 24,400 and is specific for cyclic AMP. PDE I has apparent Km values of 83 and 53 micron for cyclic AMP and cyclic GMP, respectively, whereas PDE II exhibits an apparent Km value of 330 micron for cyclic AMP. With subsaturating concentrations of cyclic AMP as substrate, the phosphodiesterase activity of PDE I is inhibited by the addition of cyclic GMP. However, PDE II activity remains unaffected by cyclic GMP even at concentrations up to 125 micron. PDE II appears to be thermostable, losing only 20% of its activity on heating at 80 degrees for 2 min. Similar treatment completely abolishes the enzyme activity of PDE I.

3',5'-Cyclic-AMP Phosphodiesterases↗

Dopamine-beta-hydroxylase in the cerebrospinal fluid of psychiatric patients.

The activity of dopamine-beta-hydroxylase (DBH) in cerebrospinal fluid (CSF) from 59 psychiatric patients has been analyzed by a highly sensitive radio-enzymatic assay. There was no sex difference in DBH, but there was a significant positive correlation with age. Probenecid administration had no effect on CSF DBH. DBH in CSF correlated positively (r = 0.60) with the plasma enzyme. Among patients hospitalized for major depressive disorder, unipolar or bipolar, schizo-affective disorder, schizophrenia, alcoholism, or personality disorders there were no significant between-group differences. Among the patients with bipolar affective disorder, DBH activity from manic patients was significantly lower than that from depressed or euthymic patients. The results are discussed with reference to the theory that the amount of DBH in CSF may serve as an indicator of central noradrenergic activity.

Adolescent↗

Haloperidol: effect of long-term treatment on rat striatal dopamine synthesis and turnover.

The short- and long-term effects of neuroleptic drugs differ both clinically and biochemically. Short-term treatment with such a drug causes a kinetic activation of striatal tyrosine hydroxylase. Long-term treatment causes a prompt activation of the enzyme which is followed by a delayed, compensatory deactivation below control levels. Tolerance also develops to the stimulating effect of haloperidol on striatal dopamine turnover.

3,4-Dihydroxyphenylacetic Acid↗

Regional changes in the activities of aminergic biosynthetic enzymes in the brains of hypertensive rats.

The activities of monoamine biosynthetic enzymes were measured in brain regions of several hypertensive rat models at various ages. The types of hypertensive rats were the spontaneously hypertensive rat (SHR) and a stroke-prone substrain of the SHR as well as DOCA-salt and renal hypertensive rats. The genetically hypertensive rats had significantly elevated blood pressures as compared to the Wistar-Kyoto control rat after 5 weeks of age. During the early development of hypertension in the SHR, the activities of tyrosine hydroxylase in the hypothalamus and corpus striatum and of dopamine-beta-hydroxylase in the hypothalamus and pons-medulla were significantly higher than in the control rats. Tryptophan-hydroxylase was also elevated in the hypothalamus in SHR. From 3 to 8 weeks of age there appeared to be a significant correlation between hypothalamic dopamine-beta-hydroxylase activity and blood pressure in the hypertensive rats. In contrast, the activities of tyrosine hydroxylase and dopamine-beta-hydroxylase were slightly decreased in the DOCA-salt and renal hypertensive rats. It is suggested that noradrenergic or adrenergic neurons in the hypothalamus may participate in the initiation of elevated blood pressure in the genetic, but not in the DOCA-salt or renal hypertensive rats.

Aging↗

Pineal protein phosphorylation during serotonin N-acetyltransferase induction.

The activity of soluble protein kinase (ATP:protein phosphotransferase,EC 2.7.1.37) and pattern of nuclear protein phosphorylation was monitored in cultured rat pineal glands during the induction of serotonin N-acetyltransferase (acetyl-CoA:serotonin N-acetyltransferase;EC 2.3.1.5)by l-isoproterenol. A nuclear protein appears to be phosphorylated during the early stages of enzyme induction but is not phosphorylated at later stages of induction. This correlates well with the need for RNA synthesis associated with the induction process. The nuclear protein was also phosphorylated when the pineal glands were treated with dibutyryl 3':5'-cyclic AMP. The soluble protein kinase activity appeared to decline during mid-to-late stages of enzyme induction, but there was no concomitant increase in the particulate protein kinase activity.

Acetyltransferases↗

Characterization of growth hormone and prolactin produced by human pituitary in culture.

Fragments of a pituitary tumor from a patient with acromegaly were grown in tissue culture. The tumor secreted both growth hormone and prolactin,which were recovered in high concentrations. The nonpurified hormones were characterized and compared to their respective counterparts obtained by extraction from normal pituitaries obtained at autopsy. The tissue culture and pituitary extracted hormones were eluted from Sephadex G-100 with the same partition coefficients. Growth hormone from both sources showed parallel dose-response displacement curves, by logit-log transformation, in both specific immunoassay and in a specific lymphocyte binding assay. Prolactin from both sources was compared in specific immunoassay using three different antisera. Parallel logit-log displacement curves were seen with one antiserum, while the other two antisera yielded non-parallel curves, indicating structural differences between prolactin from the two sources. Quantitative polyacrylamide gel electrophoresis was performed using multiphasic buffer systems previously developed for characterization of each hormone. By the criteria of joint 95% confidence envelopes of retardation co-efficient and relative free mobility, tissue culture growth hormone and prolactin were indistinguishable from their pituitary-extracted counterparts. This study demonstrates that, prior to purification, tissue culture derived hormone can be characterized by multiple criteria and compared to a standard preparation. Structural differences can be detected, as in the case of prolactin. When the hormones are indistinguishable, as in the case of growth hormone, it becomes worthwhile to increase the scale of tissue cultured production, with the prospect that tissue culture may serve as a source of hormone for both experimental and therapeutic use.

Adenoma↗