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Biomedical subjects

M J Stewart

Publications and source records attributed to M J Stewart.

At least 145 records · Page 8Linked to original sources
PubMed1988

Malaria sporozoites leave behind trails of circumsporozoite protein during gliding motility.

As Plasmodium sporozoites undergo gliding motility in vitro, they leave behind trails of circumsporozoite (CS) protein that correspond to their patterns of movement. This light microscopic observation was made using Plasmodium berghei sporozoites, a monoclonal antibody (MAb H4) directed against the immunodominant repetitive epitope of the CS protein of P. berghei, and an immunogold-silver staining (IGSS) technique. Sporozoites pretreated with agents that inhibit sporozoite motility and invasiveness did not produce trails. Sporozoites that glided on microscope slides coated with MAb H4 left behind considerably longer CS protein trails than those on uncoated slides, and the staining of these trails was more intense. The fact that the CS protein is an exoantigen continuously released as trails by motile sporozoites, together with our previous finding that anti-CS protein antibodies inhibit sporozoite motility, strongly suggests that the CS protein plays a role in gliding motility. The sensitive IGSS technique used in this study may be a useful tool in the study of the translocation of surface proteins during gliding of other apicomplexans, other protists, and bacteria.

Animals↗
PubMed1988

Ribosomal protein S14 is encoded by a pair of highly conserved, adjacent genes on the X chromosome of Drosophila melanogaster.

We describe a Drosophila DNA clone of tandemly duplicated genes encoding an amino acid sequence nearly identical to human ribosomal protein S14 and yeast rp59. Despite their remarkably similar exons, the locations and sizes of introns differ radically among the Drosophila, human, and yeast (Saccharomyces cerevisiae) ribosomal protein genes. Transcripts of both Drosophila RPS14 genes were detected in embryonic and adult tissues and are the same length as mammalian S14 message. Drosophila RPS14 was mapped to region 7C5-9 on the X chromosome. This interval also encodes a previously characterized Minute locus, M(1)7C.

Animals↗
PubMed1988

Demands on clinical chemistry services caused by drug related diagnoses.

The changing incidence of any given pathology in the catchment population leads to altered demands on the diagnostic services. Since two perceived problems in Glasgow have been solvent abuse and more recently drug abuse, a study was made of the change in numbers of requests to the clinical biochemistry services generated by patients with a diagnosis related to ingestion of drugs. The figures indicate that alcohol abuse leads to the greatest demands on the service and that this trend is increasing. Solvent abuse is a minor problem and in cases of abuse of hard drugs biochemical analyses other than the screening for drugs themselves seem to be required infrequently.

Chemistry, Clinical↗
PubMed1988

Clinical pharmacokinetics of enzyme inhibitors in antimicrobial chemotherapy.

The effectiveness of some antimicrobial agents can be enhanced by using them in combination; such combinations are termed synergistic. Where one compound potentiates the effect of a second drug they may be coformulated. Inhibition of the bacterial degradation of an active antimicrobial is the basis of clavulanate and sulbactam-potentiated penicillin combinations, and inhibition of degradative pathways in the host is the rationale behind imipenem/cilastatin therapy. Trimethoprim/sulphonamide combinations depend on the maintenance of an effective ratio for synergistic action. In order to achieve potentiation the coformulated drugs should have similar pharmacokinetics. Trimethoprim was originally matched with sulphamethoxazole, since these two drugs have similar elimination half-lives, but the significantly poorer penetration of sulphonamides, their greater non-renal clearance, the emergence of resistance, and the adverse reactions attributable to them argue against the rationale that underlies their coformulation. Time-dependent inhibition of bacterial beta-lactamases by clavulanic acid and sulbactam has extended the use of penicillins which are highly susceptible to beta-lactamase inactivation. The beta-lactamase inhibitors must penetrate to the same extent as the penicillin used with them, and be present long enough to effect inhibition; thus, rapid penetration, similar or slower elimination and equivalent volume of distribution are necessary. These requirements are met for amoxycillin/clavulanic acid, ticarcillin/clavulanic acid and ampicillin/sulbactam combinations. Clavulanic acid is absorbed orally and is given with amoxycillin. However, since sulbactam is labile by this route, the combination of sulbactam with ampicillin to form the prodrug sultamicillin has been necessary to enable an oral form to be developed. Imipenem is metabolised by renal brush-border dehydropeptidases, and may cause proximal tubular necrosis. Cilastatin was designed to inhibit this metabolism, which it effectively does, thereby both potentiating the effect of imipenem and avoiding toxicity. Appropriate matching of the kinetics of coformulated drugs is intended to maximise potentiation and minimise the risk of emergent resistance. The kinetics of the above combinations are discussed in the light of these requirements and the effects of age and disease.

Anti-Bacterial Agents↗
PubMed1987

A 1H spin echo NMR study of the HeLa tumour cell.

Phosphorylcholine, phosphorylcreatine, lactate, glutathione, glycine and leucine were identified in living HeLa cells in the first study of this cell type by 1H spin echo NMR spectroscopy. The technique has the advantage that it is non-invasive, providing detailed structural information on individual species present in the cell matrix. It has been used in this case to study the rate of energy consumption following the activation of the glycolytic pathway with glucose.

Energy Metabolism↗
PubMed1987

Off-line automated sample preparation--experience in a clinical drug investigation unit.

The authors describe an evaluation of the Du Pont Prep. off-line automatic centrifugal sample processing system, used in the authors' Drug Investigation Unit over the past two years. In comparison to liquid-liquid extraction, the authors found that assay precision has generally been improved, absolute recovery was quantitative, reliability has been good and the use of the system has resulted in notable labour saving. However, the cost per test based on a seven-year amortization of capital cost shows that the system is more expensive. Assays for urinary opiates, serum tricyclic antidepressants, serum isoxicam, serum valproate, serum metoclopramide and serum pindolol are presented and the merits of the method are compared with those for manual liquid-liquid extraction procedures.

Journal Article↗
PubMed1987

Pharmacokinetics of clavulanic acid-potentiated ticarcillin in renal failure.

The serum kinetics of an intravenous bolus of a combination of ticarcillin (TIC) (3 g) and clavulanic acid (CLAV) (0.2 g) have been determined in a number of patients with different degrees of renal failure as characterized by creatinine clearance. The volume of distribution for both drugs was unaffected by renal failure. Indices of serum and renal drug clearance were related to the degree of renal failure. TIC was cleared more slowly than CLAV. Anephric patients may have a higher serum clearance of CLAV than patients categorized by creatinine clearance as having severe renal failure; this could be due to an increase in metabolic clearance. Haemodialysis effectively clears both drugs. "Rebound" serum concentrations were consistently observed for TIC, but were observed in only one patient for CLAV. Continuous ambulatory peritoneal dialysis results in significant recovery of both drugs. The dosing requirements for the combination of TIC and CLAV in patients with renal failure are considered.

Adolescent↗
PubMed1987

Serum digoxin assays: investigation of use and abuse.

Digoxin requesting patterns were studied prospectively over a 6-month period. Clinicians were not forewarned that the study was being undertaken. Many samples received in the laboratory were taken at incorrect times after the drug had been given. This led to inappropriate action being taken in some cases. Appropriate action was taken on most patients who had toxic serum digoxin levels together with clinical signs. The role of subtherapeutic digoxin levels seems unclear as these elicit a wide variety of responses.

Digoxin↗
PubMed1987

Ultrastructural localization of the 150/130 Kd antigens in sexual and asexual blood stages of Plasmodium falciparum-infected human erythrocytes.

The subcellular localization of the 150/130 Kd antigen in Plasmodium falciparum-infected erythrocytes was determined by electron microscopy using monoclonal antibody 9B11 and immuno-gold labeling. We now find that this antigen may be associated with the membrane of newly-infected human erythrocytes and the cytoplasm of ring stage parasites. During differentiation of the parasite to the trophozoite stage, the antigens are no longer detectable on the erythrocyte membrane, while gold particles become more numerous within the parasite and in the erythrocyte cytoplasm adjacent to the parasite. As the parasites develop into schizonts, more antigen appears within the parasites, and some of it appears in the erythrocyte cytoplasm. At the segmented schizont stage, many intraparasitic gold particles are associated with rhoptries and micronemes of developing merozoites. Likewise, gold particles are associated with elements of the rhoptry-microneme complex in free merozoites. No gold particles are detected on the surface of merozoites. These antigens are found most abundantly in erythrocytes infected with gametocytes, revealing a localization pattern similar to that of mature trophozoite-infected erythrocytes. These subcellular localization patterns are similar to those described for the ring-infected erythrocyte surface antigen.

Animals↗
PubMed1986

Trimethoprim: prediction of serum concentrations from saliva measurements.

Saliva has been used in the past as a non-invasive predictor of serum drug concentration. Prediction may be made from a regression line of saliva versus serum concentration or from an equation proposed by Matin et al. (1974); such predictions have been examined for trimethoprim, a drug that has a pKa of 7.3, the degree of ionisation influencing its partition between saliva and serum. A relationship was found between serum and saliva trimethoprim concentrations. Salivary trimethoprim concentrations were marginally related to salivary flow rate, but not salivary pH. The precision and bias of prediction from linear regression and the equation of Matin et al. (1974) was considered; the equation did not describe the relationship between serum and saliva trimethoprim concentrations and we conclude that its use is inappropriate.

Adult↗
PubMed1986

Plasmodium berghei sporozoite invasion is blocked in vitro by sporozoite-immobilizing antibodies.

A monoclonal antibody directed against the circumsporozoite protein on the surface of Plasmodium berghei sporozoites inhibited sporozoite motility in vitro. These immobilized sporozoites could adhere to but not invade target cultured cells. Other sporozoite-immobilizing agents also inhibited sporozoite invasion into cultured cells and did not prevent sporozoite adherence. These results indicate that sporozoite invasiveness is associated with sporozoite motility. Thus, the immobilizing effect of this antibody could explain its functional activity against sporozoite invasion in vivo.

Adhesiveness↗