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Biomedical subjects

G M Scott

Publications and source records attributed to G M Scott.

At least 73 records · Page 4Linked to original sources
PubMed1984

The nature of the trifluoperazine binding sites on calmodulin and troponin-C.

We have employed 1H-nuclear magnetic resonance spectroscopy to study the interaction of the drug trifluoperazine with calmodulin and troponin-C. Distinct trifluoperazine-binding sites exist in the N- and C-terminal halves of both proteins. Each site consists of a group of hydrophobic side-chains brought into proximity by the Ca2+-dependent juxtaposition of two alpha-helical segments of the protein, each, in turn, belonging to a different Ca2+-binding site in the protein half. The trifluoperazine-induced inhibition of the biological activating ability of calmodulin appears to result from conformational restrictions conferred upon the protein by the bound drug.

Animals↗
PubMed1983

The mobility of calcium-trigger proteins and its function.

Trigger activity implies the transfer of the energy of a signal to some amplified (energy) response. Actions in cells, from calcium concentration changes to major protein reorganization are discussed here. The changes must be fast, so mobile polymers must be involved. The first step is the calcium on/off binding to its receptor, calmodulin, troponin C or a comparable protein. Calcium binding is to a loop, EF-hand, between helices. The structures and internal mobilities of these proteins are described using nuclear magnetic resonance and the temperature dependence of NMR shifts. It is suggested that these proteins illustrate a general working hypothesis that proteins made from interacting helices as opposed to beta-sheet proteins will have relatively easy internal main chain motions. Loops connecting the helices then provide particularly obvious read-out points, for example of the initial message of calcium binding. These and other regions of loose structure appear to be associated with highly charged sequences. The further transfer of the trigger message is to highly mobile sequences in troponin I, troponin T and tropomyosin.

Amino Acid Sequence↗
PubMed1983

An effective dosage regimen for prophylaxis against rhinovirus infection by intranasal administration of HuIFN-alpha 2.

Before the prophylactic effect of human interferon alpha 2 (HuIFN-alpha 2) can be tested against naturally acquired rhinovirus infection in a large-scale field trial, it is desirable to show that self-administration of the drug is practical, and to determine the smallest well-tolerated dose likely to produce a worthwhile effect. Here we report that self-administered intranasal interferon can be effective, and show how prophylaxis against rhinovirus infection is affected by both the quantity of interferon, and the interval between a dose and virus challenge. Finally, the medication regimen suggested for use in field trials (3.85 MU 3 times/day) was tested in a double-blind, placebo-controlled trial in volunteers. Although virus challenge was at a time when those being treated with interferon would be most susceptible, a substantial protective effect was still demonstrated.

Administration, Intranasal↗
PubMed1983

Comparative intranasal pharmacokinetics of interferon using two spray systems.

Physician-administered and self-administered interferon (IFN) nasal sprays were compared by measuring residual IFN recovered from the nose at intervals following single doses. Amounts of IFN recovered five minutes after administration and the decay curves of recoverable antiviral and immunoreactive IFN with time were variable between volunteers but similar for both methods. It follows that a self-administered IFN spray would be suitable for future trials of IFN in upper respiratory infections. It was also confirmed that IFN persists in the nose for at least 24 h and is not all recovered by nasal washing, suggesting that it may be bound to, then slowly released from, nasal mucosal cells.

Administration, Intranasal↗
PubMed1983

Effects of cloned interferon alpha 2 in normal volunteers: febrile reactions and changes in circulating corticosteroids and trace metals.

Six healthy volunteers were given single intramuscular injections of an ascending dose schedule of human interferon alpha 2 (Hu IFN alpha 2) from Escherichia coli. At a dose of 3 X 10(6) U, all of the volunteers had febrile reactions with influenza-like symptoms as previously described for purified natural leukocyte interferon. Significant rises in serum 11-hydroxycorticosteroids and falls in plasma zinc levels were observed at this highest dose. Although there was a reduction in the febrile reaction complex, the simultaneous administration of indomethacin with a "toxic" dose of interferon did not alter the changes in white cells, corticosteroids, or trace metals. Nonspecific effects must be considered in the therapeutic activity of interferon.

11-Hydroxycorticosteroids↗
PubMed1983

Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers.

In a double-blind, placebo-controlled study, self-administered intranasal human interferon alpha A produced by recombinant DNA technology was given both before and after virus challenge with a respiratory coronavirus. The incidence of colds, the severity of symptoms and signs, and virus replication were all reduced in subjects receiving interferon as compared with those given placebo.

Administration, Intranasal↗
PubMed1982

Interferon: pharmacokinetics and toxicity.

Interferons disappear rapidly from the serum of animals and man, and the kidney may be the major site of interferon destruction. The relevance of serum levels of interferons to their therapeutic activity has not been clearly established, particularly as the stimulation of host defence mechanisms by interferons may be important. Relatively low serum levels of antiviral activity are seen after intramuscular injections of fibroblast interferon compared with those after the same dose of leucocyte interferon. Injections of very pure leucocyte and lymphoblastoid interferons from several sources cause fever, headaches, malaise and myalgia associated with a corticosteroid response and probably with inflammatory prostaglandin synthesis. These reactions become less with repeated dosing but very large doses of lymphoblastoid interferon have been shown to cause liver damage and serious metabolic disturbances. Treatment with moderate doses of exogenous interferons may occasionally be associated with the development of neutralizing antibodies.

Animals↗
PubMed1982

Purified interferon as protection against rhinovirus infection.

In a double-blind placebo-controlled study a preparation of human leucocyte interferon purified by affinity chromatography using a monoclonal antibody and applied by repeated nasal sprays reduced the incidence and severity of colds in volunteers challenged with human rhinovirus 9. Although interferon itself caused some symptoms, these were minor compared with the clinical colds. Interferon activity was still detectable in nasal washings as long as 26 hours after the last dose in about half the volunteers on active treatment.

Administration, Intranasal↗
PubMed1982

An immunoradiometric assay of serum interferon using a monoclonal antibody.

An immunoradiometric assay for human interferon-alpha (HuIFN-alpha) has been adapted for the assay of low concentrations of HuIFN-alpha in human serum. The sensitivity of the assay is 5 to 10 IU/ml and the coefficient of variation less than 10%. The assay was shown to compare well with a biological (antiviral) assay in the measurement of serum interferon following intramuscular injection of HuIFN-alpha in nine volunteers. Serum interferon was also measured in the serum from 250 normal human donors. Two donors appeared to have detectable levels of HuIFN-alpha.

Antibodies, Monoclonal↗
PubMed1981

Toxicity of interferon.

The effects of partially purified human leucocyte interferon (PIF) and of a preparation purified by passage twice through a monoclonal antibody affinity chromatography column (NK21F) were compared with those of a control solution in healhty volunteers. After intramuscular injections both interferon preparations caused rises in pulse rate and body temperature, changes in circulating white cell counts, and various unpleasant symptoms, the most common of which were headache, malaise, and fever. Slightly lower doses of NK21F were given, and this was reflected in lower peak serum concentrations. Mean symptom scores, however, were not lower after NK21F than after PIF. Local inflammatory reactions eight hours after intradermal inoculations of these interferons were similar. Purification of interferon using a monoclonal antibody does not reduce the facets of its activity considered in this study. They are therefore inherent in the leucocyte interferon type selected by the antibody.

Adult↗
PubMed1980

Failure of human fibroblast interferon to protect against rhinovirus infection.

Volunteers were treated with fibroblast interferon or placebo nose drops for four days. On the second day, they received a challenge with rhinovirus type 4. There was no difference in the clinical symptoms or viral shedding between the two groups. The possible reasons for this result are discussed.

Administration, Intranasal↗