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Biomedical subjects

C L Johnson

Publications and source records attributed to C L Johnson.

At least 181 records · Page 10Linked to original sources

Beta-Adrenergic receptors and catecholamine-sensitive adenylate cyclase of the human placenta.

Beta-Adrnergic receptor and beta-adrenergic sensitive adenylate cyclase were demonstrated in membrane fractions of human placenta. Placental membranes from normal term pregnancies bound the beta-adrenergic antagonist (-)[3H]dihydroalprenolol to a single saturable class of sites (Kd = 2.31 +/- 0.23 nM; n = 9; maximal capacity, 112 +/- 9 fmol/mg). Competition for binding was stereoselective for (-)isomers of propranolol, and beta-adrenergic agonists displayed competition for the placental receptor in the order (-)isoproterenol greater than (-)epinephrine greater than (-)norepinephrine, typical of a beta 2 type receptor. Beta-Adrenergic receptor was present in placental tissue as early as 10 weeks gestational age, and binding capacity decreased slightly with advancing gestation. [3H]Dihydroalprenolol binding was coupled to epinephrine-stimulated adenylate cyclase activity throughout gestation. The subcellular distribution of both beta-adrenergic receptors and epinephrine-stimulated adenylate cyclase suggest their localization primarily in nonbrush border membrane fractions, presumably from plasma membranes more closely related to the fetal rather than to the maternal circulation. Epinephrine-sensitive adenylate cyclase was not present in purified brush border preparations which were directly exposed to maternal blood in the intervillous space.

Adenylyl Cyclases↗

Data systems support for a large, long-term carcinogenic (ED01) study.

Data Systems Support for the 24,192 mouse toxicological ED01 study at the National Center for Toxicological Research required technology heretofore not available in the field of Toxicology. The large volume of data expected from this study, multiple studies being conducted simultaneously, and accurate and timely information in a usable timeframe, were problems solved by the data systems personnel. NCTR's Integrated Research Support System was initiated for this study.

Animals↗

Studies on histamine H2 receptors coupled to cardiac adenylate cyclase. Effects of guanylnucleotides and structural requirements for agonist activity.

In particulate preparations from guinea-pig ventricle, histamine in the concentration range 10(-6)--10(-3) M caused a 3--5fold stimulation of adenylate cyclase activity which was dependent on the presence of GTP. The effects of fourteen analogs of histamine were examined on this cyclase preparation. Five of the compounds studied proved to be partial agonists relative to histamine while nine others had essentially the same intrinsic activity as histamine. The intrinsic activities of the partial agonists were increased by GppNHp to the extent that dimaprit, which was a partial agonist in the presence of GTP, became a full agonist in the presence of GppNHp. The relative potencies of the full agonists as activators of the cyclase were found to correlate with the relative potencies on physiologically defined H2 receptor systems. Activation of the cyclase by histamine, as well as by several of the agonist analogs, including dimaprit and tolazoline, was completely blocked by the H2 antagonist cimetidine, but was not affected by pharmacologically relevant concentrations of the H1 antagonist mepyramine, the beta-blocker alprenolol, or the alpha-blocker phentolamine. The results suggest that all the agonists studied probably interact with a common H2 receptor site on the cardiac muscle cell leading to activation of adenylate cyclase. The accompanying increase in cyclic AMP is presumably responsible for the chronotropic and inotropic effects of histamine and related compounds on cardiac muscle.

Adenylyl Cyclases↗

Adenylate cyclase from human decidua parietalis.

Adenylate cyclase (EC 4.6.1.1) activity was demonstrated in membrane fractions of human decidua parietalis. Adenylate cyclase activity was associated with membrane fractions of decidua but not chorion or amnion. Prostaglandins PGE1 and PGE2 but neither PGD2 nor PGF2 alpha stimulated this activity at gestational ages 18 to 40 weeks. Fluoride and guanosine triphosphate stimulated decidual adenylate cyclase; however, epinephrine-stimulated adenylate cyclase activity was demonstrable only in the presence of guanosine triphosphate. The possible roles of adenylate cyclase activity in the decidua are discussed.

Adenylyl Cyclases↗

Differences in localization of insulin receptors and adenylate cyclase in the human placenta.

The interactions of hormones with plasma membranes in the human placenta were characterized for specific fetal and maternal components. The microvillus brush border membrane, which is exposed to maternal blood in the intervillous space, was markedly enriched in specific insulin receptors but contained no hormone-sensitive adenylate cyclase. On the other hand, a basal plasma membrane fraction, which is presumably exposed more directly to fetal hormones, contained adenylate cyclase which was sensitive to prostaglandins, epinephrine, and fluoride but was not enriched in insulin receptors or other brush border markers. This study demonstrates separate fetal and maternal aspects of placental-hormone interactions. This separation and the relative impermeability of the placenta to hormones may allow for independent maternal and fetal components of the interaction of hormones with the placenta.

Adenylyl Cyclases↗

Physical growth: National Center for Health Statistics percentiles.

Anthropometry is an effective and frequently performed child health and nutrition screening procedure. The value of physical growth data depends on their accuracy and reliability, how they are recorded and interpreted, and what follow-up efforts are made after identification of growth abnormality. The new National Center for Health Statistics percentiles can be used to improve identification of potential health and nutritional problems and to facilitate the epidemological comparison of one group of children with others.

Adolescent↗

Components of the difference in hemoglobin concentrations in blood between black and white women in the United States.

Hemoglobin and the per cent transferrin saturation (TS) distributions of 742 black and 3074 white women drawn from a large probability sample of the US civilian noninstitutionalized population (HANES I) were examined to ascertain the magnitude and nature of an observed systematic difference in hemoglobin levels. This significant hemoglobin difference was primarily related to a different relationship between hemoglobin and TS for blacks and whites, and not related to differences in TS between the races. This difference between the races in the relationship between hemoglobin and TS explained almost all of the difference in hemoglobin concentration at the mean, the median and higher percentiles, and half or more of the difference at the first and third percentiles of the cumulative hemoglobin distributions of the white and black populations sampled. The practical implication of these findings is that white hemoglobin diagnostic criteria (standards) are inappropriate for blacks, and vice versa, both at the mean and at the lower hemoglobin levels of clinical interest.

Adolescent↗

Immunologic staging of prostatic carcinoma: three years of experience.

The immunological specificity of prostatic acid phosphatase has been demonstrated previously in the laboratory and used in a small number of patients. Our findings in 96 patients using gel immunodiffusion with an acid phosphatase antiserum in the study of bone marrow aspirates and lymph nodes are reported.

Acid Phosphatase↗

Therapy with cromolyn sodium.

Cromolyn is a prototype of a new series of drugs, the pharmacologic activities of which may offer an entirely new approach in the treatment of asthma. Whereas bronchodilator drugs and steroids act primarily at tissue sites to counteract the effects of various toxic mediators released from tissue mast cells, cromolyn prevents the release of such mediators from mast cell membranes. The advent of cromolyn sodium therapy has been recognized as a significant advance by the pharmaceutical industry, which is rapidly developing a series of cromolyn-like drugs with similar properties. Many of these compounds are active orally, and some preliminary investigations suggest that they also could be clinically effective. Cromolyn has therapeutic value in immunologic and nonimmunologically induced bronchospasm, being particularly suited for conditions amenable to long-term prophylactic therapy. The risk-to-benefit ratio of cromolyn sodium therapy is excellent. Cromolyn sodium is an important adjunct in the treatment of asthma. By topical administration the drug has been effective in seasonal and perennial rhinoconjunctivitis and in selected cases of gastrointestinal allergy to foods.

Adolescent↗

Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide.

D-Lysergic acid diethylamide and D-2-bromolysergic acid diethylamide are competitive antagonists of the histamine activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); E.C. 4.6.1.1] in broken cell preparations of the hippocampus and cortex of guinea pig brain. The adenylate cyclase is linked to the histamine H2-receptor. Both D-lysergic acid diethylamide and D-2-bromolysergic acid diethylamide show topological congruency with potent H2-antagonists. D-2-Bromolysergic acid diethylamide is 10 times more potent as an H2-antagonist than cimetidine, which has been the most potent H2-antagonist reported, and D-lysergic acid diethylamide is about equipotent to cimetidine. Blockade of H2-receptors could contribute to the behavioral effects of D-2-bromolysergic acid diethylamide and D-lysergic acid diethylamide.

Adenylyl Cyclases↗