Biomedical subjects

D S Lawrence

Publications and source records attributed to D S Lawrence.

62 records · Page 4Linked to original sources

PubMed1984

Chemical mutation of enzyme active sites.

New active sites can be introduced into naturally occurring enzymes by the chemical modification of specific amino acid residues with the use of appropriately designed coenzyme analogs. The resultant semisynthetic enzymes can have catalytic activities very different from those of the corresponding native enzymes. For example, papain has been converted into a highly effective oxidoreductase by covalent modification of the sulfhydryl group of the active site cysteine residue (Cys25) with flavins such as 8-bromoacetyl-10-methylisoalloxazine. Thus, it is now possible to enhance the catalytic versatility of existing enzymes through the process of "chemical mutation" of the active site.

Anaerobiosis↗

PubMed1984

Protein kinase C phosphorylates the synthetic peptide Arg-Arg-Lys-Ala-Ser-Gly-Pro-Pro-Val in the presence of phospholipid plus either Ca2+ or a phorbol ester tumor promoter.

The synthetic nonapeptide Arg-Arg-Lys-Ala-Ser-Gly-Pro-Pro-Val is a substrate for in vitro phosphorylation by a partially purified preparation of rat brain protein kinase C, with Kmapp of about 130 microM. The closely related peptide kemptide was a much weaker substrate, bovine serum albumin was not a substrate and the peptide Arg-Arg-Lys-Ala-Ala-Gly-Pro-Pro-Val was a weak inhibitor of the enzyme. Protein kinase C-catalyzed phosphorylation of histone III-S and the nonapeptide are regulated by identical mechanisms since with both substrates the reaction required added phospholipid and either Ca2+ (1mM) or TPA (200 nM TPA). Our findings show that polypeptides containing multiple basic residues followed by the sequence Ala-Ser can be substrates for TPA-stimulated phosphorylation by protein kinase C.

Animals↗

PubMed1982

Asthma and beta-blockers.

In a randomized, blind crossover study in 14 hypertensive patients with asthma, involving placebo and chronically administered (3 weeks) equipotent beta1-blocking doses of atenolol 100 mg once daily and metoprolol 100 mg bid, atenolol and metoprolol produced a similar fall in blood pressure. Atenolol caused significantly (p less than 0.05) less bronchospasm in terms of fewer asthmatic attacks, more asthma-free days, less frequent sensations of moderate to very severe, wheeziness and less effect on the evening peak flow rate. It was concluded that, in patients with asthma who require beta blockade, atenolol is the preferred agent, co-prescribed with a beta2 stimulant.

Adolescent↗

PubMed1979

Chronic pleurisy in systemic lupus erythematosus treated with pleurectomy.

Pleural involvement, clinically and radiologically, is common in systemic lupus erythematosus but it is usually transient and rarely presents a management problem. In the two cases described here unremitting pleural pain was the dominant symptom. After failure of conservative treatment pleurectomy was performed in both cases with symptomatic relief.

Adult↗

PubMed1978

Cytomegalovirus infection and the Guillain-Barré syndrome.

A fatal case is described of the Guillain-Barré syndrome due to cytomegalovirus infection, which was associated with hepatitis, myocarditis and viral pneumonia. Previous cases, which have usually run a benign course, are reviewed. Attention is drawn to the possible adverse effect of steroid therapy.

Adrenal Cortex Hormones↗

PubMed1975

The chest radiograph in ankylosing spondylitis.

In a study of 42 patients with ankylosing spondylitis, upper lobe fibrosis was present in six (14-3%) patients. All the patients with upper lobe fibrosis had total spinal ankylosis, and half showed peripheral joint involvement. A further 13 patients (30-9%) had other focal pulmonary abnormalities compared with only six (14-3%) of a group of age-matched controls. There was no correlation between the radiological extent of the disease (spinal changes and pulmonary involvement) and any of the haematological or biochemical parameters measured. Treatment with radiotherapy was not responsible for these changes.

Adult↗

PubMed1973

Haematology and biochemistry of ankylosing spondylitis.

Forty men with ankylosing spondylitis have been reviewed clinically, radiologically, haematologically, and biochemically, and the results of the last two compared with a male group of rheumatoid patients and a control group. In the patients with ankylosing spondylitis the haemoglobin levels were much higher and the E.S.R. significantly lower than in the rheumatoid group, and the E.S.R. in the patients with ankylosing spondylitis was unrelated to disease activity as evidenced by pain. The alkaline phosphatase level was raised in 19 cases and in most was derived from bone. Though 10 patients had abnormal globulin levels, the albumin levels were normal, as was renal function in all cases.

Adult↗

PubMedDate not supplied

Caged regulators of signaling pathways.

Although inhibitors can implicate individual protein kinases in specific signal transduction pathways, simple reversible inhibitors are unable to define both the time of initiation and the duration of protein kinase activity. How long must a specific protein kinase remain active in a particular transduction cascade to ensure that the message results in the appropriate cellular response? What is the precise temporal assembly order of individual components of an intracellular signaling complex? What, if any, temporal crosstalk is there between individual members of bisecting signaling pathways? Caged protein kinase inhibitors, as well as caged protein kinases, should serve as useful tools for temporal studies of signal transduction. We have prepared both a caged cyclic AMP-dependent protein kinase and a caged inhibitor of this enzyme. Upon photolysis, the functional activities of both species are dramatically unleashed in vitro. We have also explored both the activation and the inhibition of the cyclic AMP-dependent protein kinase-driven signaling pathway in rat embryo fibroblasts with these caged species via microinjection, and have now demonstrated that the activity of signal transduction pathways can be controlled by light in living cells.

Animals↗