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Biomedical subjects

R Sutherland

Publications and source records attributed to R Sutherland.

At least 91 records · Page 5Linked to original sources
PubMed1985

Efficacy of topical mupirocin against an experimental Staphylococcus aureus surgical wound infection.

The efficacy of topically-applied mupirocin was evaluated against an experimental surgical staphylococcal wound infection in the guinea-pig. A suture impregnated with Staphylococcus aureus was inserted into a superficial wound, and topical therapy with mupirocin ointment was started 24 h after infection. In non-treated wounds, the bacterial counts increased to greater than 10(6) organisms/wound in the majority of animals at 24 h, remaining at this level for up to seven days. Therapy with placebo ointment (polyethylene glycol base) was ineffective, whereas twice daily application of mupirocin ointment resulted in elimination of the staphylococci. Mupirocin was as effective as topically-applied fusidic acid cream in reducing the bacterial counts of infected wounds.

Administration, Topical↗
PubMed1985

Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use.

Mupirocin (pseudomonic acid A), an antibiotic produced by Pseudomonas fluorescens, showed a high level of activity against staphylococci and streptococci and against certain gram-negative bacteria, including Haemophilus influenzae and Neisseria gonorrhoeae, but was much less active against most gram-negative bacilli an anaerobes. Nearly all clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis, including multiply resistant strains, were susceptible (mupirocin MIC, less than or equal to 0.5 microgram/ml). There was no cross-resistance between mupirocin and clinically available antibiotics, and the selection of resistant variants in vitro occurred at a low frequency. Mupirocin was highly bound (95% bound) to the protein of human serum, and activity was reduced 10- to 20-fold in the presence of human serum. The activity of mupirocin was not greatly influenced by inoculum size but was significantly enhanced in acid medium. In tests of bactericidal activity, MBCs were 8- to 32-fold higher than MICs and the antibiotic demonstrated a slow bactericidal action in time-kill tests, resulting in 90 to 99% killing after 24 h at 37 degrees C.

Anti-Bacterial Agents↗
PubMed1984

CFU-C inhibitors in aplastic anaemia.

Peripheral blood lymphocytes from 15 patients with marrow aplasia were tested for their ability to inhibit the proliferation of normal granulopoietic precursor cells (CFU-C) in agar culture, relative to the inhibitory effect of normal lymphocytes studied in parallel. Eight of the 15 patients with marrow aplasia had lymphocytes which were significantly less inhibitory to normal CFU-C than controls whereas 3 patients had lymphocytes which were significantly more inhibitory. Two further patients who had recovered from marrow aplasia were also studied. The effect of patient's plasma and normal plasma on normal CFU-C proliferation was also studied and in 1 case a potent inhibitor of granulopoiesis was demonstrated. In 9 cases CFU-C could be cultured from patient's marrow, and parallel studies examining the effects of lymphocytes or plasma on patient's CFU-C were performed in these. All 9 patients had low numbers of marrow CFU-C. In none of the 9 marrow samples tested was inhibition by patient lymphocytes significantly greater than normal controls. The results highlight the heterogeneity inherent in the study of aplastic states and serve to underline the importance of controls. In only a minority of cases (20%) was lymphocyte suppression of normal granulopoiesis by lymphocytes from patients with aplastic anaemia significantly greater than normal lymphocyte suppression.

Adolescent↗
PubMed1983

Chromosome assignment of monoclonal antibody-defined determinants on human leukemic cells.

Hybrids formed between human acute lymphoblastic leukemia (ALL) cells and mouse myeloma have been used to determine the chromosomal location of genes required for the expression of several monoclonal antibody (mAb)-defined cell surface antigens on ALL cells. Cloned hybrids were tested for antibody binding, immunoprecipitation of the relevant protein, chromosome isoenzyme markers and karyotype. Two antigens of those studies could be definitively mapped, OKT10/p45 to chromosome 4 and BA-2/p24 to chromosome 12. mAb BA-2 reacts with the same protein as another mAb designated 609-29 (anti-teratocarcinoma). Reactivity with the latter mAb has been previously shown to segregate with chromosome 12.

Animals↗
PubMed1983

Receptor for transferrin may be a "target" structure for natural killer cells.

Human transferrin receptors detected by monoclonal antibody OKT9 appear to be well expressed on cell types known to provide sensitive targets for natural killer (NK) cells. The possibility that transferrin receptors are recognized by NK effector cells has been investigated by three series of experiments: (i) analysis of the correlation between sensitivity to natural killing and the proportion of transferrin receptor-positive cells in different cell lines, (ii) study of the relationship between levels of transferrin receptor expression in cell lines and their capacity to competitively inhibit recognition and killing of the target cell K562 by NK cells, and (iii) comparison of affinity-purified soluble proteolytic fragments of the transferrin receptor and HLA-A, -B molecules for their ability to inhibit the natural killing effect. The data indicate that the transferrin receptor can provide a "target" structure for NK cells. Because transferrin receptors are ubiquitously expressed on normal and malignant proliferating cells, these observations have interesting implications for the possible function of NK cells in vivo.

Antibodies, Monoclonal↗
PubMed1983

Effect of two antibiotics on human granulocyte activities.

As part of a study of the effects of antibiotic therapy upon human phagocytes, ampicillin and cefaclor were each administered orally to nine healthy adult subjects in a single dose of 500 mg. There was a significant difference in their effects on neutrophil myeloperoxidase (MPO) (EC.1.11.1.7) activity (P less than 0.05) in that ampicillin depressed, but cefaclor enhanced, the measured enzyme activity. Concomitantly ampicillin decreased but cefaclor increased, the rate of phagocytosis of staphylococci, the effects of the two antibiotics also being significantly different (P less than 0.05). Direct measurements of intracellular killing of staphylococci did not change. In four patients with chronic bacterial infections who had low levels of neutrophil MPO activity, treatment with cefaclor led to a significant increase in the MPO levels to within the normal range. Three patients responded satisfactorily to cefaclor despite having previously filed to respond to antibiotics which were similarly active in vitro against the causative bacteria. These findings lead us to suggest that, in patients with chronic refractory infections, attention must be given to the effect of drugs on the host defences in addition to a careful choice of the most active antibacterial agent.

Adult↗
PubMed1982

Structural features of the cell surface receptor for transferrin that is recognized by the monoclonal antibody OKT9.

The monoclonal antibody OKT9 reacts specifically with the receptors for transferrin on human cells (Sutherland, D. R., Delia, D., Schneider, C., Newman, R. A., Kemshead, J., and Greaves, M. F. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4515-4519; in Leukemia Markers (Knapp, W., ed) pp. 157-160, Academic Press, New York) and has been used to isolate and characterize this receptor. The receptor is a dimeric glycoprotein (Mr = 180,000) composed of two subunits (Mr = 90,000) and has a pI of approximately 5.2. The transferrin receptor appears to be a transmembrane molecule and is phosphorylated, the phosphate group being predominantly on serine residues. The cell surface form of the molecular possesses both complex and high mannose oligosaccharide chains, which do not appear to have a direct role in antibody (OKT9) binding. The molecule can be cleaved into a Mr = 70,000 fragment from the cell surface, suggesting that the major part of the receptor is exposed to the extracellular environment. The released Mr = 70,000 fragments are not disulfide-linked and possess the antibody (OKT9)- and transferrin-binding sites. Cross-linking studies using radiolabeled transferrin suggest that two molecules of transferrin are bound to each Mr = 180,000 receptor dimer.

Antibodies, Monoclonal↗
PubMed1982

Expression of human transferrin receptor is controlled by a gene on chromosome 3: assignment using species specificity of a monoclonal antibody.

The monoclonal antibody OKT-9 has been shown to recognize the human transferrin receptor. We have exploited the species specificity of OKT-9 to map a gene controlling human transferrin receptor expression to chromosome 3, using human-mouse somatic cell hybrids. The gene for the human transferrin receptor and the gene controlling transferrin expression may be linked in humans.

Animals↗
PubMed1982

Monoclonal antibodies defining markers with apparent selectivity for particular haemopoietic cell types may also detect antigens on cells of neural crest origin.

Monoclonal antibodies described as reacting with particular subsets of haemopoietic cells were screened against a variety of neuronal cell lines to further investigate their true specificity. While some reagents, e.g., monoclonal anti-cALL (J5), were found only reactive with haemopoietic cells, other monoclonals, e.g., BA1, BA2, NA134, OKT6, and OKT9, also bound to neuronal cells. Further investigation into the cross-reactivity of these antibodies to a variety of neural crest derived cell lines indicated that, with the exception of OKT9, differential binding patterns to different lines were obtained. This suggests that haemopoietic cell subsets and neural crest derived tissues can share similar differentiation antigens. For monoclonals OKT9 and BA2 this observation was confirmed biochemically, showing that it is not just antigenic determinants but similar molecular weight cell surface antigens that are shared between subsets of the two major cell types. A similar analysis using monoclonal antibodies raised against human neuronal cells or cell lines again indicates that some antigens appear unique to neural tissue while others are shared by haemopoietic cell subsets.

Antibodies, Monoclonal↗
PubMed1982

Distribution of amoxicillin and clavulanic acid in infected animals and efficacy against experimental infections.

The therapeutic effects produced by formulations of amoxicillin plus clavulanic acid (BRL 25 000A and BRL 25 000G) were compared with those of amoxicillin and clavulanic acid separately against a variety of infections produced by amoxicillin-susceptible and beta-lactamase-producing (amoxicillin-resistant) bacteria. The infection models studied included intraperitoneal infections, a mouse pneumonia, experimental pyelonephritis, and local lesions caused by Staphylococcus aureus and Bacteroides fragilis. The distribution of amoxicillin and clavulanic acid in infected animals after the administration of amoxicillin-clavulanic acid was evaluated by measurement of the concentrations of the substances present in specimens collected at the sites of infection. The results showed that both amoxicillin and clavulanic acid were well distributed in the animal body after the administration of amoxicillin-clavulanic acid formulations, being present in significant concentrations at various sites of infection, e.g., peritoneal washings, pleural fluid, pus, and infected tissue homogenates. In a number of cases, the amoxicillin concentrations measured after the administration of BRL 25000 were higher than those found after treatment with amoxicillin alone, presumably as a result of inhibition of bacterial beta-lactamases by clavulanic acid at the site of infection. The ability of clavulanic acid to protect amoxicillin in vivo was confirmed by the efficacy of amoxicillin-clavulanic acid formulations in the treatment of the infections studied, most of which were refractory to therapy with amoxicillin.

Amoxicillin↗
PubMed1982

Classification of beta-lactamase-producing bacteria.

The resistance of bacteria to beta-lactam antibiotics, penicillins or cephalosporins, is usually associated with the production of beta-lactamase enzymes which are capable of inactivating these compounds. A number of recent surveys have reported a significant increase in the frequency of isolation of beta-lactamase-producing strains of bacteria from infections in general practice in the United Kingdom. A wide variety of bacterial beta-lactamases with different properties have been described and it is now recognised that most bacteria produce a chromosomally-mediated beta-lactamase which is characteristic of each species. In addition, Gram-negative bacteria may acquire beta-lactamases which are mediated by plasmids which are readily transferable by cell to cell contact. Schemes for the classification of bacterial beta-lactamases are outlined.

Bacteria↗
PubMed1981

P-24: a human leukemia-associated and lymphohemopoietic progenitor cell surface structure identified with monoclonal antibody.

This study was directed at surface structures that are found on human lymphohemopoietic progenitor cells in normal and leukemic bone marrow. A monoclonal antibody was produced against an acute lymphoblastic leukemia (ALL) cell line of the pre-B phenotype; this antibody (BA-2) was used to demonstrate a cell surface polypeptide of approximately 24,000 mol wt that migrates similarly in both reduced and nonreduced form. This polypeptide, p24/BA-2, was shown by immune precipitation and gel electrophoresis and cell distribution studies to be different from HLA-DR and gp 100/cALLa. p24/BA-2 was present on the surface of 77% (54/70) of cases of non-T, non-B ALL; BA-2 staining was less bright or nondetectable in surface Ig+ (SIg+) chronic lymphocytic leukemia (CLL) and T ALL and nondetectable on peripheral T and B lymphocytes. Approximately 3% of bone marrow mononuclear cells were p24/BA-2+, and these cells were E rosette-, surface (SIg-), and nonphagocytic. Marrow TdT+ progenitor cells were frequently p 24/BA-2+. Results suggest that p24/BA-2 represents a surface structure present on lymphohemopoietic bone marrow progenitor cells and that most common types of ALL bear the p25/BA-2 structure.

Antibodies↗
PubMed1981

Mapping cell surface antigen expression of haemopoietic progenitor cells using monoclonal antibodies.

A library of monoclonal antibodies which show selective reactivity with particular cells or gene products (e.g. HLA-DR, glycophorin) of different cell lineages in the haemopoietic system has been compiled. Using these probes in conjunction with the fluorescence-activated cell sorter (FACS) the pattern and sequence of cell surface antigenic expression on haemopoietic progenitor cells have been mapped. A cell is identified in bone marrow which has a unique membrane phenotype and the nuclear enzyme terminal deoxynucleotidyl transferase. Its composite phenotype is identical to that seen in the common variant of acute lymphoblastic leukaemia (ALL). It is suggested that this cell is a putative B lineage progenitor which provides the major target for ALL. Detailed analysis of erythroid differentiation with monoclonal antibodies on the FACS reveals an intriguing pattern of antigenic expression in which HLA-DR, glycophorin and band III appear in sequence. HLA-DR (Ia-like antigen) may be present on all or most committed haemopoietic progenitor cells and could play an important role in cell interactions regulating early haemopoiesis.

Animals↗
PubMed1981

Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin.

A murine monoclonal antibody (OKT9) raised against human leukemic cells binds to a wide variety of leukemia and tumor cell lines and to a minority of leukemia cells taken directly from patients. Fetal thymus and liver are strongly reactive as are some normal, immature hemopoietic cells and activated lymphocytes. Reactivity with OKT9 appears to correlate with proliferation status in both normal and malignant populations. Biochemical analysis indicates that this structure is a approximately equal to 180,000-dalton glycoprotein with two disulfide-bonded subunits of approximately equal to 90,000-daltons. Isolation of the transferrin receptor from a T-cell line (MOLT-4) indicates that it also has a dimeric approximately equal to 180,000-dalton structure. Radio-labeled transferrin bound to its receptors can be specifically precipitated by the monoclonal OKT9, although the latter does not bind transferrin itself, indicating that the antigenic structure defined by this antibody is likely to be the transferrin receptor.

Animals↗
PubMed1981

BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans.

BRL 17421 is a new semisynthetic beta-lactam antibiotic with an unusual spectrum of antibacterial activity. The compound exhibits exceptional stability to a wide range of bacterial beta-lactamases and is active against the majority of Enterobacteriaceae, including strains highly resistant to many of the penicillins and cephalosporins currently available. Among the clinical isolates of Enterobacteriaceae tested, the frequency of strains resistant to BRL 17421 was found to be low, and there was a slow rate of emergence of resistance during in vitro studies. BRL 17421 was highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase-producing strains. The compound was markedly less active against Pseudomonas aeruginosa and Bacteroides fragilis than against the Enterobacteriaceae. Against the gram-positive bacteria, BRL 17421 showed a very low level of activity. BRL 17421 was found to be 85% bound to human serum, and the antibacterial activity was diminished two- to fourfold in the presence of human serum. Against experimental infections in mice, the activity of BRL 17421 reflected the properties observed in vitro. Studies in human volunteers showed unusually high and prolonged serum concentrations of the compound after parenteral dosage, with a serum half-life of about 5 h, and approximately 85% of the dose was recovered unchanged in the urine. BRL 17421 was poorly absorbed after oral administration. The compound was well tolerated after intramuscular and intravenous administration in volunteers, with no adverse side effects.

Animals↗