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Biomedical subjects

J L David

Publications and source records attributed to J L David.

At least 55 records · Page 3Linked to original sources
PubMed1988

Lectin-like binding of pertussis toxin to a 165-kilodalton Chinese hamster ovary cell glycoprotein.

Chinese hamster ovary (CHO) cells cluster in the presence of pertussis toxin, a response that is correlated with the ADP-ribosylation of a Mr = 41,000 membrane protein by the toxin. A ricin-resistant line of CHO cells (CHO-15B) which specifically lacks the terminal NeuAc----Gal beta 4GlcNAc oligosaccharide sequence on glycoproteins did not cluster in response to pertussis toxin. These cells do contain the Mr = 41,000 protein substrate for the enzymatic activity of the toxin which suggests that pertussis toxin, like certain plant lectins, does not bind to or is not internalized by the CHO-15B cells. There was no evidence of pertussis toxin binding to gangliosides or neutral glycolipids isolated from CHO cells but the toxin bound to a Mr = 165,000 component in N-octyglucoside extracts of CHO cells that had been separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotted to nitrocellulose. Plant lectins from Ricinus communis and Erythina cristagalli detected a similar size band in CHO cells and also did not react with CHO-15B cells. Unlike pertussis toxin, these plant lectins recognized two other major bands in CHO cell extracts and reacted best after sialidase treatment of nitrocellulose transfers containing CHO cell extracts. Conversely, sialidase treatment abolished binding a pertussis toxin and wheat germ agglutinin, a plant lectin that reacts with multivalent sialic acid residues on glycoproteins, to the Mr = 165,000 band. Purified B oligomer of pertussis toxin also uniquely detected a Mr = 165,000 component in CHO cell extracts while the A subunit of pertussis toxin was unreactive. These results indicate that pertussis toxin binds to a CHO cell glycoprotein with N-linked oligosaccharides and that sialic acid contributes to the complementary receptor site for the toxin. In addition, they suggest that a glycoprotein may serve as a cell surface receptor for pertussis toxin and that this interaction is mediated by a lectin-like binding site located on the B oligomer.

Adenosine Diphosphate Ribose↗
PubMed1988

Comparison of type 2 and type 6 fimbriae of Bordetella pertussis by using agglutinating monoclonal antibodies.

Two types of fimbriae have been identified on the pathogenic gram-negative organism Bordetella pertussis. Monoclonal antibodies to these fimbriae were produced to better understand the role of fimbriae as serotype-specific agglutinogens and to investigate the antigenic relationship between these fimbriae. Three monoclonal antibodies were identified that specifically agglutinated B. pertussis cells containing the U.S. Reference Factor 2 agglutinogen, and six monoclonal antibodies were produced that agglutinated only those strains containing the U.S. Reference Factor 6 agglutinogen. Indirect immunofluorescence studies and immunogold electron microscopy demonstrated that these monoclonal antibodies bind to an outer membrane component on serotype-specific strains of B. pertussis. All of the monoclonal antibodies reacted with native or partially assembled type-specific fimbriae but not with monomeric fimbrial subunits as indicated by Western blot (immunoblot) analysis. The fimbrial agglutinogens recognized by the monoclonal antibodies were also uniquely reactive with either U.S. Reference Factor 2 or 6 antiserum (Eldering agglutinogen 2 or 6 polyclonal antiserum) in an indirect ELISA. No cross-reactivity of the monoclonal antibodies with the unrelated fimbriae was observed in any of the comparative immunological studies. Some of the monoclonal antibodies agglutinated certain strains of B. bronchiseptica, suggesting that this closely related species can contain antigenically similar fimbriae. These monoclonal antibodies should prove useful for further structural and functional analysis of Bordetella fimbriae and for studies on the role that these antigens play in prevention of infection and disease.

Agglutination Tests↗
PubMed1987

Prevention of aorta-coronary bypass graft occlusion. Beneficial effect of ticlopidine on early and late patency rates of venous coronary bypass grafts: a double-blind study.

The efficacy of coronary bypass grafting obviously being linked to graft patency, it is compulsory to look for any innovation that could improve the patency rate. Ticlopidine, an antiplatelet drug, was tested against placebo in a double-blind trial: 173 patients (475 grafts) subjected to venous coronary artery bypass grafting were randomly treated with ticlopidine (250 mg twice daily) or placebo from the second postoperative day for 12 months. Graft patency was assessed by digital angiography on days 10 (99.4% of the patients), 180 (98.2%), and 360 (91.7%). The effect of treatment on platelet aggregation and bleeding time were measured concomitantly; a clear-cut effect was demonstrated at each interval. Intention-to-treat graft-by-graft analysis shows that ticlopidine significantly reduced the graft occlusion rate on day 10 (7.1% versus 13.4%, p less than 0.05), day 180 (15.0% versus 24.0%, p less than 0.02), and day 360 (15.9% versus 26.1%, p less than 0.01). Sequential grafts to the left anterior descending coronary artery, with side-to-side anastomosis to diagonal branch(es), are less frequently occluded than individual grafts. On the contrary, grafts to endarterectomized vessels occlude more frequently. Individual patient-by-patient analysis shows that patency of all grafts at each study time, is more frequent in the ticlopidine group. The difference is significant when one considers patients without sequential or endarterectomized grafts. The difference is also present at each study time: day 10 (84.4% versus 66.7%, p less than 0.05), day 180 (74.4% versus 52.3%, p less than 0.05) and day 360 (75.0% versus 52.5%, p less than 0.05). Results are even more impressive if one excludes from analysis the four patients in the ticlopidine group in whom administration of the drug was delayed. This supports previous suggestions that early therapy is necessary. These results show that graft occlusion occurs mainly in the first 6 postoperative months. The incidence of occlusion is significantly reduced by ticlopidine therapy.

Angiography↗
PubMed1985

Subacute subdural hematoma as the first symptom in a child with hemophilia A.

The authors reported a case of subacute subdural hematoma in a 14-month-old child suffering from mild hemophilia (Factor VIII, activity: 2.5%). Removal of hematoma under the cover of replacement therapy has been performed safely and has led to recovery without any clinical sequelae. Computerized tomography appeared very useful as an atraumatic method of examination in hemophiliacs. Discussion deals with the problems associated with management of intracranial hemorrhages in hemophiliacs and emphasizes the need of prompt adequate medical and surgical treatment to prevent irreversible damage to the brain.

Brain Damage, Chronic↗
PubMed1984

Effect of ticlopidine on saphenous vein bypass patency rates: a double-blind study.

The effects of ticlopidine, a new antiplatelet agent, on graft patency rate was investigated in a group of 150 consecutive patients undergoing aortocoronary bypass graft procedures. In a double-blind study, two groups of 75 patients each received ticlopidine (250 mg twice daily) or a placebo during a three-month period. Graft patency was evaluated by repeat angiography in 38 patients and by rest and stress myocardial scintigraphy in 93. Combined angiographic and scintigraphic analysis was performed in 36 patients. The biological effects of ticlopidine on platelet activity were assessed by bleeding time and appropriate ex vivo tests. Graft patency was evaluated in 131 patients (87%). Evaluation was performed at the end of the three-month therapy period in 77 patients (Groups T1 [ticlopidine] and P1 [placebo]) and five months later in 54 patients. The total graft attrition rate was 10.1% in Group T1 compared with 20.3% in Group P1 (p less than 0.1). Excluding patients with discordant biological data, the attrition rate was 7.1% for Group T1 compared with 21.8% for Group P1 (p less than 0.02). There was no difference between the subgroups evaluated five months after the end of therapy. Ticlopidine appears to be an effective means of protecting graft patency as long as the biological effects of the drug are present. This protective effect disappears when the drug is discontinued, which suggests that ticlopidine should be prescribed for a longer period, at least for the first year after operation.

Coronary Artery Bypass↗
PubMed1982

Inhibition of 5-hydroxytryptamine-induced and -amplified human platelet aggregation by ketanserin (R 41 468), a selective 5-HT2-receptor antagonist.

Ketanserin, a selective 5-HT2-receptor antagonist, inhibits the reversible aggregation induced by 5-hydroxytryptamine (5-HT) in human platelet-rich plasma (PRP). In this respect, the compound is equipotent to cyproheptadine and more active than methysergide (IC50: 1.66 x 10(-8) M, 1.44 x 10(-8) M and 5.62 x 10(-8) M respectively). Ketanserin is active against 5-HT-induced platelet aggregation after both in vitro and oral administration to human volunteers. At concentrations up to 500 times in excess of the IC50 for 5-HT-induced platelet reactions, ketanserin does not affect the aggregation induced by ADP, epinephrine, collagen or Thrombofax, the prostaglandin biosynthesis of thrombin-stimulated platelets, nor the active uptake of 14C-5-HT by platelets. 5-Hydroxytryptamine amplifies the human platelet aggregation induced by threshold concentrations of ADP, collagen, epinephrine, norepinephrine and induced irreversible aggregation of platelets pre-sensitized with Thrombofax. This amplification by 5-hydroxytryptamine results in a platelet response typical for the potentiated agonist; for the combination of the monoamine with collagen, the serotonergic amplification results in enhanced aggregation, release of beta-TG and PF4 and excessive formation of TXB2. Ketanserin, after both in vitro and oral administration to man reduces the amplified response to the level of the potentiated agonist. The present evidence suggests the presence of functional 5-HT2 receptors on the human platelet, different from those involved in the uptake of the monoamine.

Blood Platelets↗
PubMed1981

5-HT2-receptor blockade in the treatment of heart failure. A preliminary study.

Ketanserin (R 41 468), a quinazoline derivative, has been shown to be a selective blocker of 5-HT2 receptors. The drug was administered intravenously (10 mg given over a 3 min period) to 8 patients with severe cardiac failure already treated with digitalis, diuretics, and, in 4 cases, vasodilators. R 41 468 produced a significant fall in right-atrial, pulmonary-artery, pulmonary-wedge, and systemic arterial pressures. Systemic dynamic and total pulmonary vascular resistances were also reduced. Cardiac and stroke-work indices both increased, Heart rate remained unchanged. The platelet aggregation index, assessed in 2 patients, was initially low and was nearly normal 15 min after administration of a single dose of R 41 468.

Adult↗