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Biomedical subjects

R B Clark

Publications and source records attributed to R B Clark.

At least 235 records · Page 13Linked to original sources

Naloxone in the parturient and her infant.

Eighteen women in labor received analgesia with moderately large total doses of meperidien. Various doses of naloxone (8, 12, 18, 27, 40, or 60mug/kg of body weight) were given intravenously to the mothers before delivery in an attempt to find the dose that would prevent neonatal narcotic depression. Maternal and neonatal blood gas values, Apgar scores, and postnatal neurobehavioral examinations were used to assess the effects. Infants born of mothers who had received neither meperidine, promethazine, nor naloxone served as controls. After the naloxone injection, the mothers showed an improvement in consciousness and blood gas values. When the study infants, as a group, were compared with control infants, there was very little difference in blood gas values or neurobehavioral examination. Infants in the groups receiving naloxone in doses of 18, 27, and 40mug/kg compared most favorably with the control infants, indicating that naloxone may be effective in preventing neonatal narcotic depression.

Adult↗

Aspartokinase I-homoserine dehydrogenase I of Escherichia coli K12 (lambda). Activation by monovalent cations and an analysis of the effect of the adenosine triphosphate-magnesium ion complex on this activation process.

The dehydrogenase activity of the aspartokinase I-homoserine dehydrogenase I complex isolated from Escherichia coli K12 is subject to a cooperative activation by K+ or Rb+, which is characterized by a Hill coefficient of approximately 2. Ionic strength has little effect on the Hill coefficient for this activation process; however, high ionic strength appears to increase the enzyme's affinity for K+ and decrease its affinity for Rb+. The Vmax of the K+-activated dehydrogenase is greater than that of the Rb+-activated dehydrogenase. The results of a study of the competition between K+ and Rb+ in the activation process suggest the presence of an activated species containing both K+ and Rb+. The cooperative activation by K+ is antagonized by Na+ via a process that is noncooperative with respect to Na+. The MgATP-2- complex, a substrate for the kinase activity of aspartokinase I-homoserine dehydrogenase I, has a marked effect on the K+ activation of the dehydrogenase activity. Kinetic studies of this effect of MgATP-2- on the K+ requirement of the dehydrogenase at pH 8.9 indicate that: (a) activation by a monovalent cation is essential in the presence as well as in the absence of MgATP-2-; (b) the concentration of K+ required to activate fully the dehydrogenase is reduced in the presence of MgATP-2-; (c) activation of the dehydrogenase by K+ is noncooperative in the presence of MgATP-2-; and (d) the maximum velocity for the dehydrogenase catalyzed oxidation of homoserine is greater in the presence of MgATP-2- than in its absence. Based on these results, a simple model consistent with these data is proposed. Destruction of the kinase activity and the threonine sensitivity of the aspartokinase-homoserine dehydrogenase complex by treatment with 5,5'-dithiobis(2-nitrobenzoic acid) or by incubation at pH 9 also converts the K+ activation of the dehydrogenase from a cooperative to a noncooperative process. Marked protection of the enzyme against loss of threonine sensitivity at pH 9 is afforded by MgATP-2- plus K+ and homoserine. The apparent molecular radius of the enzyme complex as determined by gel filtration at pH 8.85 in the presence of threonine or MgATP-2- plus K+ and homoserine is dependent on the enzyme concentration. The observed apparent molecular radii of 70 A at high enzyme concentrations and 61 A at low enzyme concentrations are consistent with the enzyme's undergoing a concentration-dependent dissociation from a tetrameric to a dimeri

Adenosine Triphosphate↗

Infiltrative retinopathy in systemic lymphoma.

A 48-year-old woman with a diffuse well-differentiated lymphocytic lymphoma developed an unusually extensive bilateral infilfrative retinopathy during a period of quiescence of her systemic illness. Although radiation therapy to each orbit initially induced clearing of the infiltration and significant improvement in visual acuity, late visual acuity loss due to retinal and optic nerve changes ensued.

Cobalt↗

Factors influencing the effect of hormones on the accumulation of cyclic AMP in cultured human astrocytoma cells.

The characteristics of the effects of catecholamines, prostaglandins, and adenosine on the adenosine 3',5'-monophosphate (cAMP) content of human astrocytoma cells are described. Catecholamines interact with a typical beta-adrenergic receptor, i.e., the order of potency of catecholamines is isoproterenol larger than or equal to epinephrine greater than norepinephrine greater than dopamine, and propranolol is an inhibitor but phentolamine is not. The prostaglandins interact with a receptor that recognized PGE-1, PGE-2, and PGA-1 but not PGF-2-alpha. The effects of PGE-1 are blocked by 7-oxa-13-prostynoic acid, indomethacin, and meclofenamic acid in a rapid, reversible manner. The cells contain another adenylate cyclase-linked receptor that recognizes adenosine and the adenine nucleotides but not guanosine, deoxyadenosine, or adenine. Theophylline and other methylxanthines are competitive inhibitors of the effect of adenosine. Each class of effector appears to stimulate adenylate cyclase by interacting with a structure-specific receptor. This follows from the observation that the effect of each class of agonists can be blocked selectively by the various inhibitors and is consistant with the observation that co-addition of different agonists results in additive effects on accumulation of cAMP. The magnitude of the effect of any of the classes of agonists can be influenced by a variety of factors, some of which may be related to the peculiarities of growth in culture: (1) The cells secrete cAMP into the medium, and the magnitude of this secretion for a given rise in intracellular cAMP is different for different agonists. (2) The exposure of the cells to catecholamines or prostaglandins leads to a loss of responsiveness to a subsequent challenge by the same agonist. The magnitude of the agonist-induced loss of responsiveness is dependent on the concentration of the agonist and the time of exposure. The process is at least partially agonist specific in that exposure of cells to isoproterenol can lead to greater than 90% loss in catecholamine responsiveness with less than 20% loss in responsiveness to prostaglandins. (3) The responsiveness of the cells also changes as a function of the age of the culture and as a function of cell density. (4) Finally, it can be demonstrated that cells maintained in culture for prolonged periods (months to years) may lose responsiveness to specific agonists while responsiveness to other agonists remains unchanges or actually increases. The advantages and disadvantages of the use of cells in culture for studies of the regulation of cAMP metabolism are discussed.

Adenine↗

Maternal and neonatal effects of 1% and 2% mepivacaine for lumbar extradural analgesia.

Continuous lumbar extradural analgesia with mepivacaine was administered to two groups of patients in normal labour. One group (26 patients: 1% mepivacaine) received a mean total dose of 342 mg (4.93 mg/kg) per patient, and developed a mean blood concentration of mepivacaine at delivery of 1.82 mug/ml. The neonatal umbilical vein concentration was 0.84 mug/ml. The other group (30 patients: 2% mepivacaine) received a mean total dose of 776 mg (11.65 mg/kg) per patient, and developed a mean blood concentration of mepivacaine at delivery of 3.47 mug/ml. The neonatal umbilical vein concentration was 2.61 mug/ml. Four of the infants of mothers who received 1% mepivacaine were depressed (1-min Apgar score 6 or less), and six of the other group were depressed also. Usually, depression appeared to be related to obstetric factors, rather than to analgesia. Eleven of the 56 infants had umbilical vein mepivacaine concentrations of 3 mug/ml or greater; of these, three were depressed. This does not agree with the concept that the toxic threshold for mepivacaine is 3 mug/ml. In both groups a significant linear correlation was obtained between umbilical vein concentration and total dose of mepivacaine. A maximal dose of 12 mg/kg maternal weight in the non-obese or 12 mg/kg lean body mass in the obese is suggested for continuous extradural analgesia with mepivacaine, although healthy mothers and infants may tolerate much more.

Anesthesia, Epidural↗

The selective in vivo incorporation and metabolism of radioactive putrescine in the adult male rat.

Putrescine (1,4, diaminobutane), a known precursor of the polyamines, spermine, and spermidine, was studied as a possible vehicle for a radioisotope scan of the prostate and other tissues rich in polyamines. Male Sprague-Dawley rats received intravenous injections (2.3 muCi/100 gm) of 3H putrescine dihydrochloride (specific activity, 107 muCi/muM). One hour after injection the ventral prostate and pancreas showed uptake of radioactivity that was three and four times greater than that of the liver, respectively. The ratio of the amount of radioactivity in the ventral prostate compared with that of abdominal wall musculature was 8:1. The pancreas-to-muscle ratio was 10:1. At 1 hr the ventral prostate contained 0.6% (0.9%/gm wet wt) of the total injected radioactivity and the pancreas, 0.5% (1.2%/gm wet wt) of the injected dose. More than 90% of the radioactivity in the rat ventral prostate, 6 hr after intravenous injection of 14C-putrescine dihydrochloride, was found to be in the form of spermine and spermidine, thus confirming previous in vitro biosynthetic studies.

Abdominal Muscles↗

Organic acids and iron translocation in maize genotypes.

Translocation of Fe was studied in WF9 (Fe-efficient) and ys(1)/ys(1) (Fe-inefficient) maize (Zea mays L.) genotypes. Iron-deficient WF9 translocated more Fe to the tops than Fe-deficient ys(1)/ys(1). Malate and citrate contents of root saps increased nearly 2-fold and aconitate increased over 4-fold in both genotypes as Fe of nutrient solutions increased from 0.1 to 3 milligrams per liter. Relative acid contents in root saps were as follows: malate > aconitate > citrate. Citric acid concentrations in stem exudates were nearly the same as in root sap. Malic acid concentrations were considerably lower in exudates than in root saps, and only a trace of aconitic acid was detected in the exudates. The concentration of Fe was 7-fold higher in exudate of WF9 than in exudate of ys(1)/ys(1) and the concentration of exudate P was about the same for both genotypes.Electropherograms of WF9 stem exudates showed that (59)Fe moved toward the anode as (59)Fe-citrate. Exudates of ys(1)/ys(1) contained insufficient (59)Fe to produce radiographs. When (59)Fe was added in vitro to ys(1)/ys(1) stem exudate, the (59)Fe moved as (59)Fe-citrate, indicating that sufficient citric acid was present in the exudate to chelate the Fe. Effectiveness of citric, isocitric, trans-aconitic, and malic acids in moving (59)Fe electrophoretically in acetate, citrate, isocitrate, trans-aconitate, and malate buffers was studied. Malic, acetic, and trans-aconitic acids were ineffective in moving Fe from the origin. Citric acid moved Fe anodically whenever present on the electropherogram and successfully competed with the other acids for Fe.Results with ys(1)/ys(1) roots indicate an absence of an efficient mechanism for transporting Fe from cortical cells to the xylem. If Fe can reach the xylem stream, the ys(1)/ys(1) genotype should be as efficient as WF9 in moving Fe to the leaves.

Journal Article↗