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Biomedical subjects

D C Watson

Publications and source records attributed to D C Watson.

118 records · Page 7Linked to original sources

The hormonal control of activity of skeletal muscle phosphorylase kinase. Amino-acid sequences at the two sites of action of adenosine-3':5'-monophosphate-dependent protein kinase.

Two tryptic phosphopeptides containing the sites on the alpha and beta subunits of phosphorylase kinase which are phosphorylated by protein kinase, dependent on adenosine 3':5'-monophosphate (cyclic AMP), have been isolated and their amino acid sequences have been determined. 32P-labelled phosphorylase kinase, containing 1.9 mol phosphate per mol enzyme, was digested with an equimolar quantity of trypsin for 2.5 min at pH 7.0, 20 degrees C. This treatment released nearly all the 32P radioactivity associated with the beta subunit as trichloroacetic-acid-soluble material. Only a small proportion of the 32P radioactivity associated with the alpha subunit was solubilised, the remainder being removed in the trichloroacetic acid pellet. The beta-subunit tryptic phosphopeptide was completely resolved from traces of the alpha-subunit phosphopeptide by gel filtration on Sephadex G-25. Further purification by peptide mapping separated the phosphopeptide into four components, each derived from the same nine-amino-acid segment of the betachain, which was found to possess the sequence: Gln-Ser-Gly-Ser(P)-Val-Ile-Tyr-Pro-Leu-Lys. The four components were produced by the partial cyclisation of the N-terminal glutaminyl residue, and by the presence of two alleles for the beta subunit in the rabbit population, which led to a valine-isoleucine ambiguity. The alpha-subunit phosphopeptide was liberated from the trichloroacetic acid pellet by redigestion with trypsin. It was the largest component in the digest which remained soluble in 5% trichloroacetic acid, and obtained in a highly purified form by a single filtration on Sephadex G-50. The peptide comprised 39 amino acids of which nine were serine and three were threonine residues. Only one residue, the serine at position three from the amino terminus, was phosphorylated. The amino-terminal sequence of the peptide was shown to be: Arg-Leu-Ser(P)-Ile-Ser-Thr-Glu-Ser-Glx-Pro-Asx-Gly. The sequences confirm the stoichiometry of the reaction and the absolute specificity of cyclic-AMP-dependent protein kinase for just two of the 200 serine residues in the enzyme. These results and an inspection of the rate of phosphorylation of a number of skeletal muscle proteins, including each enzyme of the glycolytic pathway, lead to the conclusion that cyclic-AMP-dependent protein kinase is an extremely specific enzyme. The molecular basis of this specificity is discussed.

Adenosine Triphosphate↗

The wandering pacemaker: intraperitoneal migration of an epicardially placed pacemaker and femoral nerve stimulation.

A premature child with congenital complete heart block had an epicardial single-chamber pacemaker implanted at 2 days of age. At 21 months of age, while sitting or standing, the patient's right anterior thigh muscles contracted at her pulse rate. Surgical exploration revealed a free-floating pacemaker in her peritoneum. A new dual-chamber pacemaker was implanted into the abdominal wall with resolution of the child's symptoms.

Abdomen↗

O-specific side-chain toxin-protein conjugates as parenteral vaccines for the prevention of shigellosis and related diseases.

Only indirect evidence has been cited to document that lipopolysaccharide-mediated virulence at the bacterial level and serum antibodies to the O-specific side chain of the lipopolysaccharide molecule may prevent shigellosis. Our proposed use of the B subunit of Shiga toxin as a carrier protein is based upon evidence (even more indirect) that serum antitoxin may reduce the severity of dysentery and diarrhea. Because animal models of disease may provide information inapplicable to the prediction of vaccine-induced protective immunity, we suggest that clinical trials in the population at risk should be started after successful completion of the safety and immunogenicity phases of vaccine development in laboratory animals and in the target population. Clinical studies of shigella vaccines are difficult because of the many causes of dysentery in a population with a high rate of intestinal disease.

Animals↗

Transbronchial intubation of the right pleural space: a rare complication of nasogastric intubation with a polyvinylchloride tube--a case study.

Inappropriate intubation of the tracheobronchial tree by a fine-bore nasogastric tube with a metal stylet is a well-known hazard. We report a pulmonary perforation and hydropneumothorax caused by a polyvinylchloride nasogastric tube without a stylet in a child of 13 months. The position of the tube was checked by auscultation before feeding. It would appear that the auscultatory method is inadequate in checking the correct placement of a nasogastric tube in young children. An ordinary nasogastric tube can cause pulmonary perforation.

Auscultation↗