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Biomedical subjects

D Gilbert

Publications and source records attributed to D Gilbert.

At least 145 records · Page 8Linked to original sources
PubMed1987

Pharmacokinetics and pharmacodynamics of intravenous ciprofloxacin. Studies in vivo and in an in vitro dynamic model.

The pharmacokinetics and pharmacodynamics of a 200-mg intravenous dose of ciprofloxacin were studied in normal volunteers and in an in vitro dynamic model that exposes bacteria to changing concentrations of the drug in a neutropenic setting. Peak ciprofloxacin concentrations in vivo averaged 3.2 micrograms/ml. The terminal serum elimination half-life averaged 4.2 hours. The volume of distribution of ciprofloxacin was large and consistent with extensive extravascular distribution. Slightly less than half of the dose was recovered unchanged in urine by 48 hours after infusion. The median serum bactericidal titer against a strain of Escherichia coli was 1:16 or more for at least six hours after infusion, but was only 1:2 against a strain of Pseudomonas aeruginosa immediately after the end of the infusion. Pharmacodynamic studies in the in vitro model with a simulated regimen of 200 mg administered intravenously every 12 hours demonstrated rapid and complete killing of this strain of E. coli following the first 200-mg "dose." For the strain of P. aeruginosa, an initial bactericidal effect was observed due to the eradication of susceptible subpopulations of bacteria; however, regrowth of resistant organisms was observed. These data suggest that a regimen of 200 mg administered intravenously every 12 hours results in rapid killing of susceptible bacteria. Higher doses or combination therapy may be required to prevent the emergence of resistant P. aeruginosa in this model and in the setting of neutropenia.

Bacterial Infections↗
PubMed1986

Biosynthesis of the third component of complement (C3) by the human monocytic-cell line U-937. Induction by phorbol myristate acetate.

Phorbol myristate acetate (PMA)-stimulated human monocyte-like cells (U-937) were found to synthesize the third component of complement (C3), as shown by enzyme-linked immunosorbent assay and immunoprecipitation from [35S]methionine-labelled culture supernatants. C3 synthesis occurred at a rate of about 160 ng of C3/24 h per 10(6) cells on day 7 after addition of PMA; it was blocked by cycloheximide treatment and was restored after removal of the inhibitor. SDS/polyacrylamide-gel-electrophoretic analysis of the immunoprecipitated protein showed that the size and subunit structure of the newly synthesized C3 were identical with those of plasma C3, and that a single-chain intracellular precursor was present in the cell lysates. Haemolytic assays showed that the synthesized C3 fully expressed functional activity in early culture within 4 h. After longer culture, a loss of haemolytic activity was observed. The possibility that newly secreted C3 is cleaved by U-937 cells themselves was suggested.

Cell Line↗
PubMed1986

Long-term biosynthesis of complement component C3 and alpha-1 acid glycoprotein by adult rat hepatocytes in a co-culture system with an epithelial liver cell-type.

We used a system of co-culture of adult rat hepatocytes with another epithelial cell type from rat liver to study the synthesis of two acute-phase reactants, alpha-1 acid glycoprotein (alpha 1AGP) and the third component of complement (C3), and we have obtained long-term secretion of these two proteins. After a period of adaptation corresponding to the first 2-4 days of the co-culture, hepatocytes secreted C3 and alpha 1AGP for at least 2 weeks at a mean level higher than that observed in the first days of a pure culture of hepatocytes. When pulse-chase analysis was performed on day 6 of co-culture, kinetics of synthesis of alpha 1AGP and C3 were the same as those observed on day 1 of a conventional culture of pure hepatocytes. Furthermore, intracellular and extracellular alpha 1AGP had Mr values respectively of 39,000 and of 42,000-52,000, identical with those observed in pure cultures of hepatocytes. Similarly, the molecular size and subunit structures of C3 were the same in co-culture and in cultures, indicating an identical processing of this protein. C3 produced in co-culture was also haemolytically active. Therefore, the system of adult hepatocytes co-cultured with this liver epithelial cell provides a physiological system in vitro which permits long-term synthesis of the two acute-phase reactants C3 and alpha 1AGP. This model opens the possibility to study the modulation of the synthesis of these two proteins during a long period by inflammatory agents or by hormones.

Animals↗
PubMed1986

Human retinal pigment epithelial cells in the vitreous of the owl monkey.

Cultured human retinal pigment epithelium was injected into the vitreous of owl monkeys. The epithelial cells were derived from either a foetal or an adult cell line. The five monkeys which were injected with cultured foetal cells developed substantial vitreal membranes and had retinal detachment by 2 weeks, whereas the five monkeys with cultured adult cells did not develop detachments within the period of investigation, and vitreal membranes were insubstantial. An electron-microscopic, immunohistochemical and autoradiographic study was conducted on these eyes to investigate in detail the behaviour and intraocular effects of the injected cells.

Adult↗
PubMed1986

Transcutaneous carbon dioxide monitoring during neonatal transport.

We studied the value of transcutaneous carbon dioxide (PtcCO2) monitoring during neonatal transport. Thirty-two neonates with respiratory distress were alternately enrolled in an experimental group (results of PtcO2 and PtcCO2 available for clinical management) and a control group (results of only PtcO2 available). Although differences were not significant, infants in the experimental group had more changes in the intermittent mandatory ventilation (IMV) settings during transport, and more such infants arrived at the receiving hospital with acceptable pH and PCO2 values. On arrival at the receiving hospital, two patients in the control group had acidosis and hypercarbia and were placed on IMV immediately on arrival. No such patients were encountered in the experimental group. For patients needing IMV during transport, the percentage of study time spent with PtcCO2 measurements in the normal range (35 to 45 torr) was greater for the experimental group (p less than .02). Continuous PtcCO2 monitoring during transport offers the opportunity to further decrease the risks of transporting a critically ill neonate.

Blood Gas Analysis↗
PubMed1986

Influence of medium and method on the in vitro susceptibility of Pseudomonas aeruginosa and other bacteria to ciprofloxacin and enoxacin.

Ciprofloxacin and enoxacin were two- to fourfold less active against Pseudomonas aeruginosa in calcium- and magnesium-supplemented broth compared with unsupplemented broth regardless of inoculum size, presence of serum, or use of inhibitory or bactericidal endpoints (P less than 0.01). The effect of cation supplementation was less pronounced and less consistent for Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus.

Anti-Bacterial Agents↗
PubMed1985

Modulation of complement receptors of a human monocyte cell line, U-937, during incubation with phorbol myristate acetate: expression of an iC3b-specific receptor (CR3).

The human monocyte line, U-937, derived from an individual with histiocytic lymphoma was studied for the expression of surface C3 receptors, after cultivation in the presence of phorbol myristate acetate (PMA) or T lymphocyte-conditioned medium. Receptors were detected by using EAC4b, EAC3b, EC3b, EAC3bi and EAC3d intermediates. U-937 cells, in exponential growth phase, poorly bound the intermediates; after exposure to PMA or T lymphocyte-conditioned medium, U-937 cells strongly bound both EAC3b and EAC3bi since about 50% of cells rosetted with these intermediates. This binding was totally inhibited by EDTA and by Mac-1 monoclonal antibody, suggesting the presence of only CR3 receptor types on these cells. Although U-937 cells formed rosettes with EAC3b, there was no evidence for the presence of CR1 receptors since no rosette was observed either with EAC4b or with EC3b intermediates (EC3b were prepared by coupling purified C3b to erythrocytes with N-succinimidyl 3-(2-pyridyldithio)propionate. As small amounts of factor H were present on EAC3b intermediates, incubation of EAC3b with U-937 cells induced their transformation into EAC3bi and their binding to CR3. Moreover, U-937 cells did not promote the cleavage of C3b in the presence of factor I alone, suggesting that these cells did not bear a sufficient amount of functionally active CR1. These results demonstrated that U-937 cells predominantly expressed CR3. The study of the kinetics of EAC3bi rosette formation demonstrated that CR3 expression is closely related to PMA activation. We suggest that CR3 activity could result from a phosphorylation of existing receptors.

Antibodies, Monoclonal↗
PubMed1984

[Immune disorders during postoperative peritonitis].

Despite major diagnostic and therapeutic advances, postoperative peritonitis appeared to be still associated with a severe prognosis. The failure to react to delayed hypersensitivity skin tests was recently shown to identify patients at increased risk for sepsis. In an attempt to clarify the mechanisms of this anergy, cellular and humoral immunity was studied with in vitro tests in 12 patients treated for postoperative peritonitis. Complement was decreased in 33.3% of cases and normal in the others. No significant change was found in IgG and IgM titres, but IgA concentrations were increased in 80% of cases. A decrease in the total number of lymphocytes was observed in 41.7% of patients, related to the reduction in the total T lymphocyte count. Mitogen-induced lymphocyte transformation was studied with phytohaemagglutinin, concanavalin A, pokeweed-mitogen, and tuberculin purified protein derivative. Six patients had decreased or negative response to at least three mitogens; 91,7% had no response to tuberculin. The leukocyte migration inhibition test was negative in all cases. These abnormalities in cell mediated immunity may have been related to underlying diseases (severe nutrition depletion in 7 cases), to sepsis (septic shock in 10 cases), to repeated anaesthesias and surgical procedures, and even to drugs (e.g. antibiotics). The presence of serum inhibitors may have been the cause of the anergy and further studies are required.

Adult↗
PubMed1984

Molecular mapping of a gene cluster flanking the Drosophila Dopa decarboxylase gene.

Nine lethal complementation groups flanking the Drosophila Dopa decarboxylase (Ddc) gene, have been localized within 100 kb of cloned chromosomal DNA. Six of these complementation groups are within 23 kb of DNA, and all ten complementation groups, including Ddc, lie within 78-82 kb of DNA. The potential significance of this unusually high gene density is discussed.

Aromatic-L-Amino-Acid Decarboxylases↗
PubMed1983

beta-Phenylethylamine-, d-amphetamine-and l-amphetamine-induced place preference conditioning in rats.

The conditioned place preference paradigm was used to study the reinforcing properties of beta-phenylethylamine (PEA), d-amphetamine and l-amphetamine. The results confirmed that each drug produced place preferences for a distinctive environment that had previously been paired with the drug treatment. PEA proved as effective as the amphetamine isomers, although substantially less potent. This is the first report of a reinforcing effect of PEA in the rat and supplements previous evidence that PEA is self-administered intravenously in the dog.

Amphetamine↗
PubMed1983

Regulation of the binding of C3-coated particles to human lymphocytes by human complement component H.

Human complement component H was found to modify greatly the binding of C3-coated particles to lymphocytes. We used an experimental model in which lymphocytes were mixed successively with various amounts of H and C3b-coated erythrocytes. At least three mechanisms were postulated to interpret the phenomenon: (i) release of endogenous I by lymphocytes triggered by H through specific binding sites, (ii) cleavage of iC3b by I, promoted by complement receptor type one, and (iii) inhibition of immune adherence by H. Such qualitative and quantitative changes in C3-coated particle recognition by the binding sites might mediate important functions of lymphocytes.

Binding, Competitive↗
PubMed1982

Inhibition of active E rosette forming T lymphocytes by hyaluronic acid. Evidence of a receptor for hyaluronic acid on a lymphocyte subpopulation.

Previous studies have shown the inhibition of active E rosette forming T lymphocytes by a mesenchyme associated antigen. Recent results clearly indicated that this antigen consisted in the association of a glycoprotein named hyaluronectin with hyaluronic acid. Using the active E rosette technique of Wybran and Fudenberg, we have studied the action of hyaluronic acid on T lymphocytes. We obtained evidence of the partial inhibition of active E rosette formation by hyaluronic acid in 19 of 25 healthy subjects. Among them, inhibition percentage was 45 +/- 4. This inhibition remained significant at a concentration of 22.5 micrograms/ml hyaluronic acid. Hyaluronic acid was labelled with peroxidase by the glutaraldehyde technique: 17 +/- 7% lymphocytes were stained by this preparation. The preincubation of peroxydase labelled hyaluronic acid by brain hyaluronectin lowered this staining. This is in agreement with the presence of hyaluronectin on a subpopulation of lymphocytes as it was shown by immunofluorescence techniques. In conclusion, a receptor for hyaluronic acid (hyaluronectin) was detected on a proportion of lymphocytes. These results suggest that hyaluronic acid could have an immunosuppressive activity.

Humans↗
PubMed1981

Differential binding of IgG subclasses to enzyme-treated human lymphocytes.

Human erythrocytes coated with each of the four human IgG subclasses were used to detect Fc gamma receptors on human peripheral blood lymphocytes (HPBL). Rosette formation was obtained only with erythrocytes coated with IgG3 (EA gamma 3). Neuraminidase treatment of HPBL induced rosette formation with EA gamma 1, EA gamma 2, and EA gamma 4 complexes. Pronase treatment also induced rosette formation to a lesser extent, but abolished EA gamma 3 rosetting. Trypsin treatment enhanced EA gamma 3 rosette formation. These phenomena occurred on both 'T' and 'non-T' lymphocytes. Erythrocytes coated with small quantities of IgG 3 did not form rosettes with HPBL. Neuraminidase treatment enhanced their binding, whereas pronase did not. These two phenomena occurred only on non-T lymphocytes. Rosette formation with EA gamma 1 was also obtained with lymphocytes stimulated in vitro with mitogens. After 2 days of culture, stimulated lymphocytes expressed receptors that were able to bind both EA gamma 1 and EA gamma 3 complexes. These results suggest the existence of cryptic receptors for IgG1, IgG2, and IgG4 that could be disclosed by neuraminidase and pronase treatment and exposed on stimulated lymphocytes. A hypothesis of one or several Fc gamma receptors is suggested.

Animals↗