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Biomedical subjects

G B Smith

Publications and source records attributed to G B Smith.

At least 55 records · Page 3Linked to original sources
PubMed1996

Drug substance manufacture process control: application of flow injection analysis and HPLC for monitoring an enantiospecific synthesis.

Effective process control can only be achieved through an understanding of the operating issues of the reaction. The development and use of effective and rugged analytical methods is necessary to monitor these parameters. The intent of this paper is to present some key analytical issues encountered in the synthesis of MK-0679, an LTD4 antagonist. In a key step of the compound's synthesis, a prochiral diester intermediate undergoes an enantioselective enzymatic hydrolysis (in the presence of Triton X-100) leading to the (S)-ester acid. Subsequent processing transforms the ester acid into the final product. The residual amount of the detergent in the final product, the rapid determination of the enzymatic activity and the optical purity of the final product emerged as key issues in the control of the reaction. As a solution, two techniques were utilized and are presented: flow injection analysis and HPLC.

Chromatography, High Pressure Liquid↗
PubMed1996

Rapid adaptation of myocardial calcium homeostasis to short episodes of ischemia in isolated rat hearts.

Short episodes of ischemia and reperfusion (ischemic preconditioning) have been shown to attenuate the detrimental rise in intracellular free Ca2+ ([Ca2+]i) caused by subsequent sustained ischemia. The purpose of this study was to investigate the detailed time course of [Ca2+]i during such short episodes of ischemia and reperfusion. [Ca2+]i was measured at a high time resolution by surface fluorometry and indo-1 in isolated perfused rat hearts during three episodes of 5 minutes of ischemia followed by 5 minutes of reperfusion. We found that the rise in systolic [Ca2+]i was significantly smaller during the second (191% +/- 67%) and third (194% +/- 75%) episodes of ischemia than during the first episode (289% +/- 75%, P < 0.05 vs both subsequent episodes). This attenuated rise in systolic [Ca2+]i was preserved during perfusion with low extracellular Na+ (105.5 mmol/L [Na+]o). During short episodes of ischemia and reperfusion, [Ca2+]i rises less during the second and third ischemic episode than during the first episode. Thus one transient ischemic stimulus led to a rapid adaptation of [Ca2+]i homeostasis to subsequent ischemic conditions. Such a rapid adaptation might be an important mechanism of the ischemic preconditioning phenomenon in protecting against ischemic injury.

Adaptation, Physiological↗
PubMed1995

Continuous ascitic recirculation in severe ovarian hyperstimulation syndrome.

Massive ascites, hydrothorax, acute renal failure and thromboembolism are clinical manifestations of severe ovarian hyperstimulation syndrome (OHSS) which may complicate the induction of ovulation with exogenous gonadotrophins. We report a case of severe OHSS with ascites formation in excess of five litres per day. Massive ascites and bilateral pleural effusions resulted in respiratory failure. Continuous ascitic recirculation (AR) was commenced after repeated paracentesis and i.v. fluid therapy failed to improve the patient's condition. The procedure was undertaken for a total of 15 days and rapidly resulted in marked improvement of impaired respiratory function. Febrile episodes occurred on 3 occasions, but we did not observe coagulation disturbances or adverse haemodynamic effects. Continuous AR is a safe and effective treatment of complicated severe OHSS.

Adult↗
PubMed1995

Tyrosine kinase phosphorylation of GABAA receptors.

Phosphorylation of purified bovine brain GABAA receptors by the tyrosine kinase, pp60v-src was examined. pp60v-src phosphorylated two bands of 54-62 kDa and 48-51 kDa that migrated to approximately the same position as bands recognized by antisera against the beta 2 and gamma 2 GABAA receptor subunits, respectively. Bacterially expressed proteins containing the putative large cytoplasmic loops of the beta 1 and gamma 2L subunits were phosphorylated by pp60v-src, indicating that the phosphorylation sites are located in these subunit domains. The tyrosine kinase inhibitors, genistein and the tyrphostins B-42 and B-44, inhibited muscimol-stimulated 36Cl- uptake in mouse brain membrane vesicles (microsacs). magnitude of the tyrphostin B-44-induced inhibition of muscimol-stimulated 36Cl- uptake was significantly reduced in microsacs that were lysed and resealed under conditions that inhibit phosphorylation. GABA-gated Cl- currents were also inhibited by genistein and tyrphostin B-44 in Xenopus oocytes expressing alpha 1 beta 1 and alpha 1 beta 1 gamma 2L subunits. Consequently, protein tyrosine kinase-dependent phosphorylation appears to be another mechanism of regulating the function of GABAA receptors.

Animals↗
PubMed1995

Functional domains of GABAA receptors.

The transmitter-gated ion channels mediate rapid synaptic transmission, for example, at the neuromuscular junction using acetylcholine and in the CNS using primarily the amino acids glutamate and GABA. GABAA-receptor Cl- channels share sequence homology with a superfamily of these channels including nicotinic acetylcholine receptor and inhibitory glycine receptor. In this article, Geoffrey Smith and Richard Olsen discuss recent affinity labelling and site-directed mutagenesis studies on GABAA receptors that have identified amino acid residues essential for binding of agonists and allosteric modulators as well as the ion channel wall formation. The structural domains identified are consistent with results obtained with other members of the transmitter-gated ion channel superfamily and suggest that structural models for one member of the family may apply to the others as well.

Amino Acid Sequence↗
PubMed1995

Upper limb compartment syndromes: a complication of malignant hyperthermia in a patient with ill-defined myopathy.

We report a case of compartment syndrome complicating malignant hyperthermia (MH) in a 12-yr-old girl with a history of myopathy and multiple skeletal deformities; she underwent bilateral Achilles tendon surgery. Marked oedema of both forearms became evident in the immediate postoperative period and resolved after conservative treatment. Compartment syndrome is a rare complication of MH. Early recognition and therapy may prevent the onset of muscle ischaemia and distal neurovascular deficit. The need for urgent surgery and repeated anaesthesia in the early phase of recovery from an acute episode of MH may thus be reduced.

Abnormalities, Multiple↗
PubMed1994

Identification of a [3H]muscimol photoaffinity substrate in the bovine gamma-aminobutyric acidA receptor alpha subunit.

An amino acid which appears to be involved in an agonist binding site of the gamma-aminobutyric acid type A (GABAA) receptor protein has been identified by photoaffinity labeling of affinity purified bovine receptor with [3H]muscimol and microsequencing of a chymotryptic fragment. Sequencing of a major purified labeled peptide gave the sequence Thr-Ile-Asp-Val-Phe with release of 3H label in the fifth cycle, corresponding to Phe. These 5 residues match the published sequence for the bovine alpha 1 subunit beginning at Thr61, following the chymotryptic substrate Tyr60. This sequence is found in the alpha 1-3 subunits of rat and cow and alpha 5 of rat, but not in any beta. Although previous evidence tentatively suggested that the beta subunit was the major [3H]muscimol-labeled subunit, homomeric expression studies have shown the potential for a functional gamma-aminobutyric acid binding site on all classes of subunits. The residue carrying the label, Phe65 on alpha 1, is conserved among all GABAA receptor alpha subunits, gamma 2, and delta. In addition, recent data indicated that a point mutation of Phe64-->Leu in rat alpha 1 subunit strongly decreased agonist and antagonist affinity when coexpressed with beta 2 and gamma 2 subunits in Xenopus oocytes (Sigel, E., Baur, R., Kellenberger; S., and Malherbe, P. (1992) EMBO J. 11, 2017-2023). The photolabeled Phe residue identified in this report is the bovine homolog to the Phe64 identified by the mutation studies of Sigel et al., to affect function in the rat GABAA receptor.

Affinity Labels↗
PubMed1994

Quality work improvement groups: from paper to reality.

Continuous quality improvement has resulted in the need for the development of new and exciting skills in group dynamics and in the facilitation of small group interactions. Leaders of quality work groups must use the understanding of group dynamics and leadership to maintain high performance work teams. To be effective, the team leaders and members must be aware of what is being said (content) and how things are being said (processes). Team leaders and groups can not be guaranteed effectiveness. However, development of the necessary skills in team building will ensure the likelihood of effective group processes and positive outcomes.

Decision Making, Organizational↗
PubMed1994

Role restructuring: nurse, case manager, and educator.

A quality improvement team of nursing managers and staff nurses planned and implemented a new delivery system that combines a team nursing method of care delivery and a unit-based case manager. The new unit-based case manager role is unique because in addition to case management, the role is also responsible for the education of staff on an assigned unit and meeting the educational needs of patients/families. The role has proved to be cost effective and has improved patient outcomes. This model is an effective delivery system for hospitals with limited resources for bedside care.

Humans↗