PubMed Health⌕ Search

Biomedical subjects

E J Conod

Publications and source records attributed to E J Conod.

15 recordsLinked to original sources
PubMed1978

The biologic activities of cystic fibrosis serum. II. Ultrastructural aspects of the effect of cystic fibrosis sera and calcium ionophore A23187 on rabbit tracheal explants.

Ultrastructural and cytochemical observations indicate that both cystic fibrosis (CF) sera and calcium ionophore A23187 induce a swelling or an increase in the size and possibly the number of secondary lysosomes and an increase in mucus secretion in epithelium of the rabbit tracheal bioassay system. Extended incubation of the rabbit tracheal explants with either CF or control sera produces a cytotoxic effect on the tracheal epithelium, but only after the termination of the normal bioassay time period. Comparative ultrastructural study of the effect of both CF sera and calcium ionophore A23187 on the rabbit tracheal bioassay system indicates that increased membrane permeability to calcium may be important in the production of the ciliary dyskinesia response by CF serum factor(s) in the rabbit tracheal bioassay system.

Animals↗
PubMed1977

Separation of serum ciliary dyskinesia substances from cystic fibrosis subjects.

Purified serum immunoglobulin G (IgG), derived from eight cystic fibrosis (CF) and five carrier subjects, has been shown to be responsible for the mucociliary disturbances noted in the rabbit tracheal bioassay. A small molecular substance of less than 10,000 but greater than 1,000 daltons (by Amicon filtration) was found associated with gamma-globulin fractions isolated from sera of these same cystic patients and their parents. Once separated by PM-10 ultrafiltration, this small substance was unable to promote the ciliary dyskinesia response in eight of eight CF and five of five CF carrier individuals unless pooled purified human IgG was added. In addition, the IgG-rich fraction retained by PM-10 ultrafiltration was still able to promote the ciliary dyskinesia response in the bioassay, an event noted in our earlier work with whole serum. The size of the small serum substance and its association with IgG closely corresponds to that described for the oyster test system, as well as to that produced by cultured cells derived from homozygotes and heteroxygotes for this genetic disorder. The persistence of the ability to promote mucociliary disturbances by the IgG-rich retentate PM-10 fractions may be indicative of the ineffective molecular separation by the Amicon ultransfiltration apparatus or may represent another CF-related, IgG-associated substance not influenced by ultrafiltration. Speculation The genetic disturbance of CF can be explained by the presence of a molecule(s) which has an affinity for IgG, which in turn gives rise to the various physiologic facets of this disorder. This molecule(s) is present in CF only because of a deficiency of an enzyme which normally controls its level by inactivation.

Biological Assay↗
PubMed1976

On the nature of the defect in cystic fibrosis.

Sera and lymphocyte culture media derived from cystic fibrosis (CF)-affected and carrier subjects contain ciliary dyskinesia factor (CDF) detected by our rabbit tracheal bioassay. In addition, we also find CDF in fibroblast media from these same donors and in amniotic fluid cell media derived from CF carrier or affected fetuses. In these latter instances, the media were inactive in the bioassay, but became active when mixed with purified IgG. In all instances, CDF activity was eliminated by the addition of anti-IgG. We have separated a low molecular weight fraction, between 1,000 and 10,000 M.W., from CF sera and culture media which is inactive in the bioassay until IgG is added. Presumptive and indirect evidence indicates that this fraction behaves similarly to the complement derived anaphylatoxin C3a. In addition, we have found activity in sera from CF patients and, to a lesser extent, carriers that induces degranulation of cytochalasin-B-treated human polymorphonuclear leukocytes. Since this activity appears to be in a different molecular species from that containing CDF, we postulate that the primary defect in CF is the deficiency of an enzyme whose substrates include a family of membrane-active molecules.

Amniotic Fluid↗
PubMed1975

Demonstration of human leukocyte degranulation induced by sera from homozygotes and heterozygotes for cystic fibrosis.

The ability of epsilon-amino caproic acid (EACA)-treated normal serum and of cystic fibrosis (CF)-affected and carrier sera to promote the release of lysosomal enzymes from sensitized human polymorphonuclear leukocytes (PMN) was assessed through the measurement of beta-glucuronidase and myeloperoxidase activity after exposure of these cells to the various test sera. This study was initiated to extend the analogies between preciliary dyskinesia factor (pre-CDF), separated from the cell-free media of cultures derived from CF homozygous and heterozygous individuals, and C3a anaphylatoxin. The extent of lysosomal degranulation of human PMN exposed to fresh untreated sera of each of five controls, seven CF homozygotes, and eight heterozygotes, as expressed by the amount of beta-glucuronidase releases, was 7.84% (+/- 0.934) for countrol sera, 14.01% (+/- 1.79) for CF-affected sera, and 10.61% (+/- 1.43) for heterozygous sera. The difference between CF homozygotes and control subjects is significatn (P less than 0.0001), as is the difference between CF-affected and carrier individuals (0.001 less than P less than 0.005) and between control subjects and carriers (0.001 less than P less than 0.005), when beta-glucuronidase. However, the differences between control subjects and CF heterozygous individuals are not significant. Treatment of these sera with 1 M EACA gave values for beta-glucuronidase and myeloperoxidase release which are slightly reduced when compared with those obtained with fresh, untreated samples. EACA apparently reduces the activity of beta-glucuronidase released from PMN. Amicon filtration studies of these serum samples demonstrated that degranulating ability and the presence of cilicary dyskinesia, as assessed by rabbit tracheal bioassay, are not always associated. Therefore, the relationship between pre-CDF and the degranulator activity in native CF-affected and carrier sera is unclear, in part because of the limitations inherent in the test systems employed.

Aminocaproates↗