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Biomedical subjects

K Marshall

Publications and source records attributed to K Marshall.

At least 37 records · Page 2Linked to original sources
PubMed1999

Peritrophins of adult dipteran ectoparasites and their evaluation as vaccine antigens.

Several peritrophins of larvae of Lucilia cuprina (sheep blowfly) have demonstrated potential as vaccine antigens, and some have been characterised and cloned. These proteins are tightly associated with the peritrophic matrix, a chitinous tube or sac lining the lumen of the gut of most insects. The peritrophins require strong denaturants for their removal from peritrophic matrix. We now report the preliminary characterisation of peritrophins of the adult stage of L. cuprina and Haematobia irritans exigua (buffalo fly). Similar SDS-PAGE profiles were obtained for proteins extracted in SDS or urea from isolated adult peritrophic matrices of both species. Radioiodination of urea-extracted peritrophins improved sensitivity, indicating numerous proteins of 15-75 kDa. Direct radioiodination of L. cuprina peritrophic matrix preferentially labelled high molecular weight complexes and proteins of 80-90 kDa. Two-dimensional gel analyses of a urea extract of adult L. cuprina peritrophic matrix revealed that most proteins were moderately acidic. Antibodies produced against SDS-extracted peritrophins, or against sonicated peritrophic matrices of these two flies were crossreactive. The sera also appeared to recognise SDS-extracted components of Triton X-100 treated and washed adult peritrophic matrix of the mosquito, Aedes vigilax (Skause). This profile altered as the peritrophic matrix matured. In concordance with extracts from the adult L. cuprina and H.i. exigua peritrophic matrices, proteins in the 50-75 kDa region were immunodominant. The vaccine potential of the peritrophins of these Diptera were examined following vaccination of cattle and rabbits with adult H.i. exigua or L. cuprina peritrophins. When the adult life stages of H.i. exigua or two mosquitoes, A. vigilax and A. aegypti (Linnaeus), were fed on the sera or blood of vaccinated hosts, there were no detrimental effects to any life cycle stages of these Diptera.

Aedes↗
PubMed1998

Rubber dam.

In a busy dental practice the many advantages of the routine use of dental dam for day-to-day procedures are often not appreciated. Many general dental practitioners (GDPs) are unaware of the simple and rapid techniques for placement that exist and the important role that rubber dam plays in infection control.

Air Microbiology↗
PubMed1998

Increased affinity leads to improved selective tumor delivery of single-chain Fv antibodies.

Mr 25,000 single-chain Fv (scFv) molecules are rapidly eliminated from the circulation of immunodeficient mice, yielding highly specific retention of small quantities of scFv in human tumor xenografts. We postulated that the specific retention of scFv in tumor could be enhanced by engineering significant increases in the affinity of the scFv for its target antigens. Affinity mutants of the human anti-HER2/neu (c-erbB-2) scFv C6.5 were generated by site-directed mutagenesis, which target the same antigenic epitope with a 320-fold range in affinity (3.2 x 10(-7) to 1.0 x 10(-9) M). In vitro, the Kd of each scFv correlated closely with the duration of its retention on the surface of human ovarian carcinoma SK-OV-3 cells overexpressing HER2/neu. In biodistribution studies performed in scid mice bearing established SK-OV-3 tumors, the degree and specificity of tumor localization increased significantly with increasing affinity. At 24 h after injection, tumor retention of the highest affinity scFv was 7-fold greater than that of a mutant with 320-fold lower affinity for HER2/neu. Because the rapid renal clearance of scFv may blunt the impact of improved affinity on tumor targeting, the distributions were also assayed in the absence of renal clearance (e.g., in mice rendered surgically anephric). In this model, the peak tumor retentions of the two higher affinity scFv approximated that reported previously for IgG targeting the same SK-OV-3 tumors in scid mice with intact kidneys. In contrast, the mutant with the lowest affinity for HER2/neu failed to accumulate in tumor, indicating the presence of an affinity threshold that must be exceeded for active in vivo tumor uptake. These results indicate that affinity can significantly impact the in vivo tumor-specific retention of scFv molecules.

Adenocarcinoma↗
PubMed1998

Prostanoid-induced contraction of the rabbit isolated uterus is mediated by FP receptors.

Natural and synthetic prostanoid agonists were used to study the prostanoid receptors involved in contraction of the mature, isolated uterus of virgin rabbits. The prostanoids elicited contractile responses with a rank order of potency of PGF2 alpha, fluprostenol > PGD2 > U-46,619 > PGE2 > carbaprostacyclin with mean EC50 (nM) values of 4, 6, 34, 550, 1318 and > 10,000, respectively. Carbachol, a muscarinic agonist given after the prostanoids to elicit a reference contraction, had a mean EC50 value of 1.1 microM. The results show that the mature rabbit uterus is most sensitive to prostaglandin FP agonists and, thus, can be defined pharmacologically as an FP receptor preparation. These findings may facilitative investigations into the possibility of different prostanoid receptor populations. In the absence of useful competitive FP receptor antagonists, agonist potency data is particularly useful in systems where cross-species comparisons and tissue-related factors are not involved. The potent activities of the FP agonists, PGF2 alpha and fluprostenol, in the isolated jugular vein and uterus of the rabbit suggest that these tissues may be useful for intra-species comparisons.

Animals↗
PubMed1998

Incidence of urinary incontinence and constipation during pregnancy and postpartum: survey of current findings at the Rotunda Lying-In Hospital.

OBJECTIVE: To assess the impact of pregnancy upon continence and constipation. DESIGN: A questionnaire survey. SETTING: Maternity wards in the Rotunda Lying In Hospital, Dublin, Republic of Ireland. POPULATION: 7771 women who were delivered of liveborn infants. METHODS: Questionnaires were delivered and collected by physiotherapy staff as part of routine postnatal care. RESULTS: Analysis of data using chi2 tests showed significant differences between three parity groups [primigravidae, multigravidae (2-4) and multigravidae (5+)] for symptoms of both urinary incontinence (chi2 = 119.54, df = 2, P = 0.000) and constipation (chi2 = 12.53, df = 3, P = 0.002); the incidence of both constipation and urinary incontinence increased with parity. CONCLUSION: The results of this survey have emphasised the relation between parity and postpartum incontinence which stresses the importance of early diagnosis and intervention.

Constipation↗
PubMed1997

Recombinant human and mouse purple acid phosphatases: expression and characterization.

The mammalian purple acid phosphatases (also called tartrate-resistant acid phosphatases) are expressed primarily in actively resorbing osteoclasts and activated macrophages. The enzymes are characterized by the presence of a binuclear iron center at the active site. Recent studies on transgenic mice lacking purple acid phosphatase implicate the osteoclast enzyme in both bone resorption and bone mineralization. To characterize the mammalian enzymes in more detail, particularly with respect to their substrate specificity at the low pH of the osteoclastic resorptive space (2.5-3), we have purified the recombinant human and mouse enzymes from baculovirus-infected insect cells. The properties of the recombinant mouse enzyme are compared with those of the nonrecombinant enzyme isolated from mouse spleen. The kinetics of hydrolysis of the substrates p-nitrophenyl phosphate, phosphotyrosine, and pyrophosphate and a phosphotyrosyl peptide by the recombinant human and mouse enzymes and the nonrecombinant mouse and pig enzymes were analyzed. For all the enzymes the ratio k(cat)/Km was typically approximately 10(6) M(-1) s(-1) and was higher at pH 2.5 than at 4.9. The increase was attributable to a large decrease in Km at the lower pH value. The results indicate that the enzyme exhibits high catalytic efficiency toward substrates such as pyrophosphate and acidic phosphotyrosine-containing peptides, particularly at low pH values typical of the bone resorptive space. The implications of the results for the physiological function of the enzyme are discussed.

Acid Phosphatase↗
PubMed1997

Pharmacological evidence for thromboxane receptor heterogeneity--implications for the eye.

The pharmacological activity of two novel thromboxane A2 (TxA2)-mimetics, AGN191976 and AGN192093, was investigated in vitro, using standard organ bath assays and human platelets, to determine potency and selectivity at various prostanoid (PG-) receptors. The effects of these compounds on intraocular pressure in Beagle dogs were then compared with U-46619, a widely employed and structurally different TP-receptor agonist. AGN191976 and AGN192093 were highly potent TP-receptor agonists in the rat aorta (EC50 of 0.32 and 1.3 nM, respectively) and human myometrium. Both compounds were approximately 10 to 50 fold more potent than U-46619. These contractile responses could be blocked with a potent TP-receptor antagonist, SQ29548. In human platelets, AGN191976 (EC50 = 16.3 nM) and U-46619 (EC50 = 538.3 nM) potently stimulated aggregation (TP-receptor mediated effect), whereas AGN192093 was a much weaker agonist (EC50 = 37.9 microM). AGN192093 was not a partial agonist in platelets, since it did not antagonize aggregation induced by AGN191976, U-46619, arachidonic acid or ADP. These results provide evidence for a subdivision of TP-receptors, and AGN192093 appears to be able to distinguish between TP-receptors in smooth muscle and platelets. In the Beagle dog eye, both AGN191976 and AGN192093 were highly potent and efficacious ocular hypotensives. Single 2.5 micrograms doses of drug decreased IOP by 11.4 (AGN191976) and 7.7 mm Hg (AGN192093) relative to the contralateral control eye. In contrast, U-46619 did not lower IOP. AGN191976, but not U-46619, increased outflow facility in these animals, which is consistent with their effects on IOP. Neither compound caused miosis which is FP-receptor mediated in the dog. These studies suggest the existence of heterogeneous populations of TP-receptors. AGN191976 and AGN192093, two novel TP-receptor agonists, appear to be useful tools for the pharmacological distinction of TP-receptor subtypes.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Mike Grace interviews Keith Marshall.

Keith Marshall has many achievements to his name, not the least of which is his involvement in a semi-professional jazz band. As well as continuing to work part time in a wholly private practice in Edenbridge, Kent, he is currently chief dental adviser of BUPA DentalCover and chairman of the Dental Advisory Panel. Here, Mike Grace gets to know the man behind the dentist.

Dental Staff↗