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Biomedical subjects

J A Raeburn

Publications and source records attributed to J A Raeburn.

At least 37 records · Page 2Linked to original sources
PubMed1988

First-trimester prenatal diagnosis of cystic fibrosis using fibroblasts from a deceased index child to establish haplotypes.

First-trimester prenatal diagnosis of cystic fibrosis (CF) using linked DNA markers is usually only possible if there is an index affected child to establish the haplotype of the parental chromosomes. We describe a prenatal diagnosis where fibroblasts, cultured from the skin of a deceased affected child and then held in frozen storage for 3 years, were used as the starting point for tracking the CF gene. The fetus was diagnosed as a homozygous normal and the diagnosis confirmed by immunoreactive trypsin testing after birth. It was also possible to establish heterozygosity in the aunt of the affected child.

Adult↗
PubMed1987

Inhibition of phagocyte migration and spreading by spore diffusates of Aspergillus fumigatus.

Previous studies have shown that spores of Aspergillus fumigatus inhibit phagocytosis and killing by macrophages and polymorphonuclear leucocytes. In order to identify the mechanisms of this interference with host defences, we have examined the effects of A. fumigatus spore diffusates on phagocytic cell function. For comparison, we have used spore diffusates of the non-pathogenic fungus Penicillium ochrochloron. The diffusates of A. fumigatus reduced the number of human polymorphonuclear leukocytes migrating towards a known chemoattractant by approximately 50% (p less than 0.001). In addition spore diffusates of A. fumigatus significantly decreased (p less than 0.001) the capacity of primed mouse peritoneal exudate cells to spread on glass. Spore diffusates of P. ochrochloron showed no comparable inhibitory effects. These studies have shown that spore diffusates of A. fumigatus inhibit the movement of the phagocytic cell membrane and are thus able to interfere with a primary function of phagocytic cells.

Animals↗
PubMed1987

Suppression of host defences by Aspergillus fumigatus.

An important feature of the microbicidal action of phagocytic cells is their ability to produce reactive oxygen intermediates. In an attempt to identify the mechanisms by which the fungus Aspergillus fumigatus resists normal host defences the effect of spores and spore diffusates of A fumigatus on the production of superoxide anion and hydrogen peroxide by primed rodent phagocytic cells has been measured. For comparison we have used the non-pathogenic fungus Penicillium ochrochloron. Production of these reactive oxygen intermediates in response to A fumigatus was significantly lower than that in response to P ochrochloron. A similar reduction was achieved by diffusate prepared from freshly washed spores. The inhibitory component was of low molecular weight (less than 14,000) and its effect was dose dependent. These results suggest that spores of A fumigatus fail to trigger and also inhibit the production of reactive oxygen intermediates by phagocytic cells.

Animals↗
PubMed1987

Resistance of spores of Aspergillus fumigatus to ingestion by phagocytic cells.

Phagocytic cells are believed to have an important role in the eradication of fungal spores from the lung. The ability of human and mouse cells to phagocytose the opportunistic fungus Aspergillus fumigatus has been examined, spores of the non-pathogenic fungus Penicillium ochrochloron being used for comparison. Most spores became associated with cells. Those of A fumigatus appeared to remain bound to the surface of the phagocyte rather than being ingested; in contrast, P ochrochloron spores appeared to be phagocytosed more readily, although they also were seen, in small numbers, o n the cell surface. In view of the subjective nature of these observations, the effects of spore diffusates on phagocytosis were examined. Diffusates from spores of A fumigatus were shown to inhibit phagocytosis of antibody coated radiolabelled sheep red blood cells by primed mouse phagocytic cells. Diffusates of spores of P ochrochloron had no such effect. These results suggest that when spores of A fumigatus become bound to the surface of phagocytes they are able to release a substance that inhibits their ingestion while having little or no effect on surface binding.

Animals↗
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↗
PubMed1983

Ceftazidime in cystic fibrosis: clinical, microbiological and immunological studies.

We have investigated the use of the new cephalosporin ceftazidime for the treatment of pseudomonas infection in cystic fibrosis, using 100 to 240 mg/kg intravenously daily. The clinical and microbiological results of 18 courses of therapy, lasting from 1 to 4 weeks have been satisfactory, particularly since the patients had previously proved refractory to treatment with most other appropriate antibiotics. However, in common with other anti-pseudomonal antibiotics, a first course of ceftazidime proved the most successful, subsequent courses being less effective. Three patients died because of chronic respiratory infection. In cystic fibrosis pseudomonal infections rapidly relapse after therapy and therefore we have been examining the interactions of antibiotics with relevant host defence mechanisms. In one patient who received a 4 g infusion of ceftazidime there was enhancement of neutrophil phagocytosis-triggered chemiluminescence. We conclude that, used in high doses, ceftazidime is a useful addition to the available antibiotics for therapy of pseudomonas infection in cystic fibrosis.

Adolescent↗
PubMed1982

Quantitative immunoassays for diagnosis and carrier detection in cystic fibrosis.

Quantitative immunoprecipitation and immunoradiometric assays have been developed for a protein present in the serum of cystic fibrosis homozygotes, and to a lesser extent in the serum of heterozygotes. When tested on a panel of sera from 14 cystic fibrosis patients, 29 heterozygotes and 23 controls, the immunoprecipitation assay allowed correct assignments to be made on 94% of occasions with one batch of antiserum and 95% with another. With the same panel of sera, the immunoradiometric assay allowed 94% correct assignments. It is suggested that such accuracy is the maximum that can be expected in the present state of knowledge of cystic fibrosis.

Blood Proteins↗
PubMed1980

Phagocytic cells in the human inflammatory response.

Human phagocytic cells are of crucial importance in the early responses to infection. However, tests of their function have been somewhat neglected in immunological screening. This paper summarises briefly our techniques for studying neutrophils and monocytes in skin abrasions and a simple assay of phagocytic and bactericidal function. These techniques use small volumes of blood and are suitable for inclusion in the early screening of individuals who have repeated bacterial infections.

Humans↗
PubMed1979

Prospective study of genetic counselling.

A prospective study was carried out on 200 consecutive subjects seen for counselling (consultands) for serious genetic disorders. Educational and social background of consultands and their knowledge and understanding of their particular problem were assessed before counselling, and their response was determined immediately afterwards and three months and two years later by an independent observer not concerned in the genetic counselling. The husband's educational background was particularly important in influencing a couple's comprehension of counselling. X-linked recessive and chromosomal disorders presented the most difficulties in comprehension. The counsellors' assessment of comprehension was a good guide to the consultands' comprehension as assessed at subsequent follow-up. The proportion deterred from having children increased with time and over a third had been sterilised within two years of counselling. It is suggested that follow-up after counselling should be routine, especially when the counsellor suspects that comprehension has not been good, in X-linked recessive and chromosomal disorders, and when the risks of having an affected child are considered to be high.

Adult↗
PubMed1979

Characteristics of human mononuclear phagocytes.

In this study human mononuclear phagocytes from the bone marrow (promonocytes and monocytes), peripheral blood monocytes, and tissue macrophages from the skin and the peritoneal cavity were studied with respect to their morphological, cytochemical, and functional characteristics, cell surface receptors, and 3H-thymidine incorporation in vitro. The results show similarities between mononuclear phagocytes of the three body compartments with respect to esterase staining, the presence of peroxidase-positive granules, the presence of IgG and C receptors, and pinocytic and phagocytic activity. Promonocytes are the most immature mononuclear phagocytes identified in human bone marrow, and since about 80% of these cells incorporate 3H-thymidine, they are actively dividing cells. Monocytes, whether in bone marrow or the peripheral blood, and both skin and peritoneal macrophages label minimally with 3H-thymidine and thus are nondividing cells. Since the characteristics of mononuclear phagocytes in man and mouse do not diverge greatly, it is probable that the cell sequence based on in vitro and in vivo 3H-thymidine labeling studies in the mouse holds for man as well. The successive stages of development of the human mononuclear phagocyte cell line will then be as follows: monoblasts (not yet characterized in man) divide to form promonocytes, and these cells in turn divide and give rise to monocytes that do not divide further; they leave the bone marrow, circulate in the peripheral blood, and finally become macrophages in the various tissues.

Ascitic Fluid↗