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Biomedical subjects

A Percival

Publications and source records attributed to A Percival.

At least 19 recordsLinked to original sources
PubMed1995

The survival and growth of ovine afferent lymph dendritic cells in culture depends on tumour necrosis factor-alpha and is enhanced by granulocyte-macrophage colony-stimulating factor but inhibited by interferon-gamma.

An in vitro culture system is described which allows an analysis of the signals responsible for the survival, growth and functional maturation of afferent lymph dendritic cells (ALDC), a subpopulation of migrating dermal dendritic cells involved in antigen carriage and presentation to T-cells. Purified ALDC survived and grew for up to 30 days in lymph node conditioned medium and survived 14 days in recombinant ovine (rov) TNF-alpha whereas none were detected after 24 h in rov GM-CSF, rov IFN-gamma or rh M-CSF. However, when rov GM-CSF was added to cultures along with rov TNF-alpha, increased numbers of ALDC compared with input numbers (growth) were recorded on Days 14 and 21. In contrast, when 50-200 units ml-1 of rov IFN-gamma were added to cultures of ALDC along with TNF-alpha or rov TNF-alpha plus rov GM-CSF, cell survival and growth was inhibited. Antibody blocking studies confirmed the cytokine specificity of these effects. ALDC cultured in rov TNF-alpha or rov TNF-alpha plus rov GM-CSF retained MHC Class-II and ov CD-1 antigen expression and accessory function for autologous ov CD-4 T-cell proliferation, although at reduced levels compared with freshly isolated cells. Neither fresh nor cultured ALDC expressed coagulation factor XIIIa.

Animals↗
PubMed1992

Purification and adhesion receptor phenotype of ovine bone marrow-derived haemopoietic colony-forming cells.

Ovine haemopoietic progenitor cells that form colonies (CFC) in soft agar cultures were compared to more mature bone marrow cells for their level of expression of the adhesion receptor molecules ovine (ov) CD44, ov CD11a (LFA-1) and ov CD58 (LFA-3) as well as the 175-antigen using specific monoclonal antibodies. Ov CD44, ov CD11a and ov CD58 were expressed on all CFC of the myeloid (non-erythroid) series, whereas ov CD44 and ov CD11a expression was very low or absent from a small number of blast and erythroid series CFC. Within the mature non-erythroid population of myeloid cells, neutrophils retained a low level of expression of ov CD11a. Most CFC representing all lineages strongly expressed the ov CD44 antigen. In contrast, the majority of CFC lacked the 175-antigen, as did bone marrow lymphocytes, basophils and mast cells. This property of CFC was exploited in a negative selection technique using panning and immunomagnetic beads to select CFC from other bone marrow cells with a 116-125-fold enrichment, 12-14% purity and 29-40% yield. These results demonstrate that ovine CFC express some of the molecules necessary to allow adhesion to haemapoietic stromal cells and vascular endothelium in the tissues. Future studies will concentrate on the function of the adhesion receptor molecules in medullary and extra-medullary haemopoiesis and inflammatory cell development in sheep.

Animals↗
PubMed1991

Bowel microorganisms--a target for selective antimicrobial control.

This article reviews the eight factors that determine the outcome of selective antimicrobial control (SAC) a technique aimed at the clearance of intestinal Gram-negative bacillary carriage by means of lethal faecal anti-microbial concentrations. They are as follows: (i) the carrier state; (ii) compliance; (iii) SAC aiming at prophylaxis vs treatment; (iv) minimum bactericidal concentration (MBC) of the antimicrobial; (v) dosage; (vi) pharmacokinetics; (vii) faecal inactivation; and (viii) microorganisms to be controlled. In the second part, non-absorbable SAC regimens are compared with absorbable trimethoprim/sulphamethoxazole (TMP/SMZ) and the fluoroquinolones in different clinical settings including neutropenia, intensive care, hepatic encephalopathy, liver transplantation and the salmonella carrier state. Ablation of gut carriage and superinfections are the main endpoints reviewed in this article. The newer fluoroquinolones are potent SAC agents to deal with enterobacteria. Pseudomonads are the major gap in their SAC spectrum. TMP/SMZ emerges as a SAC agent of limited value, whilst the newer non-absorbable combination of polymyxin/tobramycin seems to be the most potent SAC programme since it has activity against pseudomonads. In a third part, three current issues--the emergence of resistance, the selectivity and the tissue effect are discussed. Finally, a potent fluoroquinolone combined with oral polymyxin/tobramycin seems to be the most effective SAC programme currently available to control enterobacteria and pseudomonads in patients in whom bacterial translocation is a risk with minimal risk of resistance emerging.

4-Quinolones↗
PubMed1991

Impact of chemical structure on quinolone potency, spectrum and side effects.

Following the discovery of nalidixic acid in 1962, numerous structural modifications have been made to the quinolone nucleus to increase antimicrobial activity and improve pharmacokinetic performance. A major advance occurred during the 1980s with the discovery that a fluorine at position 6 conferred broad and potent antimicrobial activity, (e.g. norfloxacin) but still with relatively less activity for Gram-positive and anaerobic organisms than Gram-negative bacteria. Subsequent developments produced quinolones with further improvements, predominantly in either solubility (e.g. ofloxacin), antimicrobial activity (e.g. ciprofloxacin) or prolonged serum half-life (e.g. pefloxacin). Recent modifications have attempted to achieve an optimal blend of favourable properties together with minimal potential for undesirable side-effects. An example is temafloxacin with comparatively enhanced activity against Gram-positive pathogens, a balanced pharmacokinetic profile, minimal CNS penetration, and without interaction with theophylline elimination. Improvements in antimicrobial activity combined with adequate blood and tissue concentrations do offer expectancy of enhanced therapeutic efficacy for new derivatives in those infections by organisms which are 'marginally' sensitive to currently used quinolones. The possibility of resistance emerging in these organisms during treatment, should also be reduced.

4-Quinolones↗
PubMed1984

Epidemiology of penicillinase-producing Neisseria gonorrhoeae in Liverpool from 1977 to 1982.

After the 1976 outbreak of penicillinase-producing Neisseria gonorrhoeae (PPNG) infections had been controlled, less than 1 per cent of cases of gonorrhoea in Liverpool in 1977 and 1978 were caused by PPNG. Thereafter the steady increase in PPNG infections to 5.6 per cent of all cases in 1982 was associated with marked changes in epidemiological pattern, plasmids and auxotypes. In 1976 nearly all PPNG infections were acquired by young black males living in the inner city from women frequenting clubs; the PPNG were all of the African 3.2 megadalton (MD) plasmid type and of arginine-requiring auxotype. Between 1977 and 1982 female patients were increasingly ship girl prostitutes associating with seamen who constituted more than 50 per cent of the male patients. These men and other travellers introduced PPNG into Liverpool from the Far East and West Africa. In 1978 PPNG of the Asian type with 4.4 MD plasmid with or without 24.5 MD transfer plasmids were isolated in Liverpool where in 1979 all PPNG carried 4.4 MD and 24.5 MD plasmids. In 1982 strains of the 'new' African type with 3.2 and 24.5 MD plasmids were isolated as were PPNG of the Asian type that had been acquired in West Africa. Auxotyping of the 1982 isolates showed that none were arginine-requiring but three other types were identified: proline-requiring: proline-arginine-requiring; non-requiring. For the control of PPNG, a strategy based on constant vigilance, appropriate diagnostic procedures, rapidly effective treatment and determined contact tracing is needed.

Adolescent↗
PubMed1983

Susceptibilities of gentamicin-resistant Gram-negative aerobic bacilli to cefotetan and other beta-lactams.

The activity of the 7 alpha-methoxycephalosporin, cefotetan was determined against 365 infecting isolates of gentamicin- and multiply-resistant Gram-negative aerobic bacilli, and compared with those of cefuroxime, cefoxitin, cephradine, cefotaxime, ceftriaxone and ceftazidime. All proteus (4), providencia (6) salmonella (3) and serratia (2) were susceptible to 8 mg/l of cefotetan, as were respectively 90 and 81% of 42 Escherichia coli and 16 citrobacter isolates. The intrinsic activity of cefotetan was high against 237 klebsiellae (38 different serotypes), only 4 being relatively insusceptible (MICs 16- greater than 32 mg/l). Activity against pseudomonas (10 isolates) acinetobacter (15 isolates) and enterobacter (30 isolates) was poor. Overall, the activities of cefotetan were similar to those of cefotaxime, ceftriaxone and ceftazidime but ceftazidime was also active against the majority of pseudomonas, acinetobacter and enterobacter. Cefotaxime was less active than cefotetan against some cefuroxime-resistant klebsiellae. Much greater numbers of isolates were insusceptible to either cefuroxime or cefoxitin. Cephradine was the least active.

Anti-Bacterial Agents↗