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Biomedical subjects

C Loomis

Publications and source records attributed to C Loomis.

26 records · Page 2Linked to original sources

Structural requirements for long-chain (sphingoid) base inhibition of protein kinase C in vitro and for the cellular effects of these compounds.

Sphingosine, sphinganine, and other long-chain (sphingoid) bases inhibit protein kinase C in vitro and block cellular responses to agonists that are thought to act via this enzyme. To gain further insight into the mechanism of this inhibition, a series of long-chain analogues differing in alkyl chain length (11-20 carbon atoms), stereochemistry, and headgroup were examined for (a) inhibition of protein kinase C activity in vitro, (b) the neutrophil respiratory burst in response to phorbol myristate acetate (PMA), (c) the PMA-induced differentiation of HL-60 cells, and (d) the growth of Chinese hamster ovary cells. In every instance, the effects were maximal with the 18-carbon homologues, which are the same length as the predominant naturally occurring long-chain base (sphingosine). The lower potency of the shorter chain homologues was partially due to decreased uptake by cells. Small differences were obtained with the four stereoisomers of sphingosine (i.e., D and L forms of erythro- and threo-sphingosine), with N-methyl derivatives of the different sphingosine homologues, and with simpler alkylamines (e.g., stearylamine). The potency of the different headgroup analogues may be affected by the degree of protonation at the assay pH. The pKa of sphingosine was measured to be 6.7; the pKa varied among the analogues. These findings establish that the major structural features required for inhibition of protein kinase C and cellular processes dependent on this enzyme are the presence of a free amino group and an aliphatic side chain and that other groups have more subtle effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Perioperative management for resection of a malignant non-chromaffin paraganglioma of the bladder.

The perioperative management of a 39-year-old patient with a rare, catecholamine producing, non-chromaffin paraganglioma of the bladder is presented. Although the management of this patient was comparable with a patient with a phaeochromocytoma, this case was complicated by marked release of catecholamines, high requirements for vasodilator therapy preoperatively, the presence of a malignant tumour with metastases and an atypical presentation. Preoperatively the diagnosis was a non-metastatic bladder phaeochromocytoma and the blood pressure was controlled with prazosin, nifedipine and propranolol. Anaesthesia was induced with fentanyl, lidocaine, thiopentone and vecuronium and was maintained with nitrous oxide, isoflurane, fentanyl and vecuronium. The patient was haemodynamically stable throughout the operative and postoperative period.

Adult↗

Prolonged spinal analgesia in the rat with the alpha-adrenoceptor agonist oxymetazoline.

The acute intrathecal (i.t.) injection of 50, 100, 200, 250 and 300 nmol of oxymetazoline produced dose-dependent antinociception in rats assessed by tail flick and paw pressure tests. Significant antinociception was observed with all doses of oxymetazoline except 50 nmol in the paw pressure test. The ED50 values for i.t. oxymetazoline in the tail flick and paw pressure tests were 120 nmol (95% CI: 76-178 nmol) and 148 nmol (95% CI: 120-186 nmol), respectively. Oxymetazoline had a long duration of action; a single i.t. dose of 100 nmol significantly elevated tail flick latency and paw pressure threshold for 8 h. The alpha-adrenoceptor antagonist phentolamine, given i.t. 1 h after oxymetazoline, attenuated the antinociceptive effect in a dose-dependent manner. Phentolamine (50 micrograms i.t.) produced almost complete antagonism in the tail flick and paw pressure tests. These data indicate that oxymetazoline produces long lasting antinociception in the rat following i.t. injection, and that the effect is mediated by alpha-adrenoceptors in the spinal cord.

Anesthesia, Spinal↗

Sequence of an expressed human beta-tubulin gene containing ten Alu family members.

The complete sequence of a functionally expressed human beta-tubulin gene (5 beta) is presented. The amino acid sequence encoded by this gene constitutes a distinct isotype, differing from a previously described human beta-tubulin sequence at 21 positions throughout the polypeptide chain. The beta-tubulin coding sequence in 5 beta is interrupted by three intervening sequences of 1014, 117 and 4826 nucleotides. The largest of these contains ten members of the Alu family of middle repetitive sequences. Together, these regions account for sixty percent of this intervening sequence. Two of the Alu elements are juxtaposed head to tail, and share the same flanking direct repeat. The ten Alu sequences are substantially divergent, both from each other and from an Alu consensus sequence, and several contain deletions of up to half the entire sequence.

Amino Acid Sequence↗

The cholinergic system of the primitive streak chick embryo.

The presence of neurotransmitters at stages of embryonic development prior to neurulation has been demonstrated in several systems. Although the functions of these molecules at early stages of embryogenesis have not been ascertained, it is possible that they are involved in aspects of cell migration, regulation of the synthesis of macromolecules, intercellular communication, and in the transmission of positional information during gastrulation. As an initial approach to the resolution of questions concerning the function of transmitters during early development, we have begun a study of the cholinergic system in the primitive streak chick embryo (Hamburger-Hamilton stages 3 + to 5). We have found that the chick embryo: (1) can use exogenously applied choline for the synthesis of acetylcholine; (2) possesses a true acetylcholinesterase, which is predominantly in the form of the 4-6s monomer; and (3) can take up exogenous choline through a sodium-dependent, high-affinity choline transport system. To date we do not have any evidence for the presence of nicotinic or muscarinic receptors at the primitive streak stage.

Acetylcholine↗

Effect of maternal ethanol ingestion on fetal breathing movements, gross body movements, and heart rate at 37 to 40 weeks' gestational age.

The effect of maternal ingestion of ethanol (0.25 gm/kg) on fetal breathing movements, gross fetal body movements, and fetal heart rate was studied in 11 healthy pregnant women at 37 to 40 weeks' gestation. Fetal breathing movements were almost abolished within 30 minutes of the alcoholic drink and remained significantly decreased for 3 hours. The incidence of gross fetal body movements before or after ethanol was not different from that on the control day, and the fetal heart rate was not changed after maternal ingestion of ethanol.

Adult↗