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Biomedical subjects

A B Leach

Publications and source records attributed to A B Leach.

12 recordsLinked to original sources
PubMed1992

A phenylalanine in peptide substrates provides for selectivity between cGMP- and cAMP-dependent protein kinases.

Bovine lung cGMP-binding cGMP-specific phosphodiesterase (cG-BPDE) is a potent and relatively specific substrate for cGMP-dependent protein kinase (cGK) as compared to cAMP-dependent protein kinase (cAK) (Thomas, M. K., Francis, S. H., and Corbin, J. D. (1990) J. Biol. Chem. 265, 14971-14978). A synthetic peptide, RKISASEFDRPLR (BPDEtide), was synthesized corresponding to the sequence surrounding the phosphorylation site in cG-BPDE. BPDEtide retained the cGK/cAK kinase specificity demonstrated by native cG-BPDE: the apparent Km of BPDEtide for cGK was 5-fold lower than that for cAK (Km = 68 and 320 microM, respectively). Vmax values were 11 mumol/min/mg for cGK and 3.2 mumol/min/mg for cAK. The peptide was not phosphorylated to a measurable extent by protein kinase C or by calcium/calmodulin-dependent protein kinase II. Thus, the primary amino acid sequence of the peptide substrate was sufficient to confer kinase specificity. Studies in crude tissue extracts indicated that BPDEtide was the most selective peptide substrate documented for measuring cGK activity. Peptide analogs of BPDEtide were synthesized to determine the contribution of specific residues to cGK or cAK substrate specificity. Substitution of a Lys for the amino-terminal Arg did not reduce cGK/cAK specificity; neither did the exchange of an Ala for the non-phosphorylated Ser nor the removal of the 3 carboxyl-terminal residues. A truncated BPDEtide (RKISASE) served equally well as substrate (Km approximately 90 microM) for both kinases. However, restoration of the Phe, to yield RKISASEF, reproduced the original cGK/cAK specificity for BPDEtide (Km = 120 and 480 microM, respectively), primarily by decreasing the affinity of cAK. Addition of a carboxyl-terminal Phe to the peptide RKRSRAE (derived from the sequence of the cGK phosphorylation site in histone H2B) or to the peptide LRRASLG (derived from the sequence of the cAK phosphorylation site in pyruvate kinase) also improved the cGK/cAK specificity by decreasing the affinity of cAK. These data suggested that the Phe in each substrate tested is a negative determinant for cAK.

Amino Acid Sequence↗
PubMed1991

The Laryngeal Mask--an overview.

New equipment, like a new drug, encourages a high level of reporting of adverse events, which can lead to the very rapid identification of even relatively rare complications. When considering the merit of one drug versus another, unless either have major defects, then the result will depend upon the overall picture, i.e. the sum of the morbidities associated with one versus the sum associated with another. Other factors such as availability, purity, and cost will also be taken into consideration. The LM is very recent in the time scale of the history of 'anaesthesia', but it would appear to have survived the 'major defect' stage, and to have entered the trial by morbidity stage. A definite answer on the question of regurgitation and aspiration is not yet available. Present evidence indicates, however, that where there is no contra-indication to it and provided that meticulous attention is paid to mode of use, the LM can be helpful in a wide variety of situations. It is an extremely innovative, and occasionally life-saving piece of equipment, and the relatively small effort necessary to acquire skill in its use worth making. A future review will be able to incorporate the results of on-going and planned studies, and may more accurately define its place in anaesthesia and resuscitation.

Anesthesiology↗
PubMed1989

Percutaneous disc surgery.

The rationale and clinical methods of percutaneous disc surgery have been modified during the past four years. Experience with a consecutive series of 48 patients suggests that the procedure now offers results comparable to open surgery and the advantages of reduced surgical trauma.

Adult↗
PubMed1988

Use your Brain!

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Anesthesia, General↗
PubMed1985

The influence of induced hypotension and spine distraction on canine spinal cord blood flow.

Deliberate hypotension is used in scoliosis surgery to reduce the need for blood transfusion and to improve operating conditions. There are concerns, however, that hypotension may decrease spinal cord blood flow (SCBF) and thereby predispose the spinal cord to ischemic injury, particularly when it is distracted during Harrington instrumentation. In a canine model, the mean arterial pressure (MAP) was reduced to 50% of the normotensive value with sodium nitroprusside and halothane to study its effects, with and without spinal distraction, on spinal cord blood flow measured by the hydrogen clearance technique. The induction of systemic hypotension resulted in a significant decrease in spinal cord blood flow from 15.7 +/- 1.1 ml/min/100 g (control) to 10.7 +/- 4.7 ml/min/100 g. This initial decrease in spinal cord blood flow returned to normotensive values by 35 minutes following the induction of hypotension, suggesting an autoregulatory effect. This indicates that the induction of deliberate hypotension to half its normotensive mean arterial pressure is associated with a significant decrease in spinal cord blood flow that returns to normotensive levels by 35 minutes. One and two centimeters of longitudinal distraction applied during systemic hypotension did not reduce spinal cord blood flow when it was applied at least 45 minutes after the hypotension was induced. Thus, when longitudinal stretch of a magnitude approximating that used clinically during Harrington instrumentation is applied in the presence of systemic hypotension, the normal SCBF is not reduced when the autoregulating system is functioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Induction and recovery characteristics of isoflurane and halothane anaesthesia for short outpatient operations in children.

Induction and recovery characteristics of isoflurane anaesthesia were compared with halothane anaesthesia during outpatient myringotomy and placement of Sheely ventilation tubes in 101 unpremedicated children. Compared with halothane, isoflurane resulted in prolonged induction times and inferior induction scores due to increased salivation, coughing, breathholding and laryngospasm. However, when modified by halothane induction, isoflurane anaesthesia decreased induction time and improved induction scores. Induction with thiamylal 4 mg/kg did not improve induction scores significantly. Recovery times from halothane plus isoflurane and pure isoflurane anaesthesia were quicker than pure halothane and thiamylal plus isoflurane, although this was not statistically significant. Compared to halothane, anaesthetic induction using isoflurane is associated with an increased incidence of respiratory problems in unpremedicated children.

Adolescent↗
PubMed1984

The effect of dietary lipid on the lipoprotein status of the Mongolian gerbil.

The Mongolian gerbil, Meriones unguiculatus, may be a suitable animal model for the investigation of dietary lipid effects on cholesterol metabolism. The effects of dietary cholesterol, and its possible interaction with the type of dietary fat, on the lipoprotein status of this animal have not been examined previously. In the present research, the effects of adding 0.5% cholesterol to diets high in saturated (19.5% beef tallow: 0.5% safflower oil) or polyunsaturated (20% safflower oil) fats on the lipoprotein status of the gerbil were determined after 11 and 22 days of feeding. Lipoproteins (VLDL, LDL and HDL) were separated by sequential ultracentrifugation. Their cholesterol, phospholipid and protein concentrations were determined colorimetrically. In the absence of 0.5% cholesterol, safflower oil lowered the concentration (mg/100 ml) of cholesterol in each of the VLDL, LDL and HDL relative to beef tallow (BT) without greatly influencing the cholesterol distribution amongst them. The HDL carried the majority of the serum cholesterol and the VLDL transported the smallest amount. However, inclusion of 0.5% dietary cholesterol resulted in a redistribution of cholesterol amongst the lipoproteins so that the VLDL and LDL became the major and the HDL the minor carriers. Dietary cholesterol also brought about a rise in the VLDL and LDL concentrations (mg/100 ml) of cholesterol, phospholipid and protein and altered the VLDL and LDL compositions. No such changes were observed in the HDL, indicating that the HDL are relatively resistant to any of the possible effects of cholesterol feeding measured in this experiment. The specific mechanisms responsible for the changes observed in the lipoprotein status of the gerbil remain to be elucidated.

Animals↗