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Biomedical subjects

D Gilbert

Publications and source records attributed to D Gilbert.

At least 55 records · Page 3Linked to original sources

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

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

[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

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

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

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

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

Cytoskeletal elements in neurons.

Neurotubules and neurofilaments are homologous with cytoplasmic microtubules and microfilaments which are seen with the electron microscope in most plant and animal cells. Their subunits are transported to the growth cone of the outgrowing axon, where the subunits are added to the distal ends of the neurotubules.

Animals

[Augmentation of HL-A A9 antigen in malignant melanoma, principally in metastatic or recurrent forms. Apropos of 105 cases of melanoma of which 34 were serious forms].

HLA-A and B phenotypes of 105 patients suffering from malignant melanomas were determined, with special regard for metastatic form or relapse. A highly significant increase of the HLA-A9 antigen is seen (X2 = 17.47); such data had already been shown by van Wijek [2], but other authors did not find this abnormality when studying melanomas whose histologic form was not specified.

HLA Antigens

Steroidal control of the release of the preovulatory surge of luteinizing hormone in the rat.

Experiments were carried out on 4 day cyclic rats or immature rats induced to ovulate by administration of pregnant mare serum gonadotrophin. Removal of the ovaries and adrenal glands at 17.00 h of pro-oestrus, i.e. after the critical period, prevented the appearance of the surge of LH. Sham-operation or removal of only one of the sets of glands had no effect. This indicates that the preovulatory increase in the concentration of oestradiol is not solely responsible for the surge of LH; the presence of a steroid, secreted by the ovaries and adrenal glands in the late afternoon of pro-oestrus, is also required. Attempts were made to reinstate the surge of LH in ovariectomized, adrenalectomized rats by administration of one of the steroids normally secreted in late pro-oestrus. Corticosterone, 20alpha- and 20beta-hydroxy-4-pregnen-3-one and 17alpha-hydroxyprogesterone all had no effect. Progesterone injected at the time of the operation stimulated the release of LH but only after the plasma concentration had reached its maximum 3--5 hr after injection. Testosterone also stimulated the release of LH some hours after administration.

Adrenalectomy

Gentamicin and tobramycin nephrotoxicity. A morphologic and functional comparison in the rat.

Fischer 344 rats were treated with tobramycin or gentamicin, 40 mg/kg/day, for up to 10 days or with tobramycin, 120 mg/kg/day, for up to 14 days. Serum creatinine and BUN at the time of sacrifice were determined, and kidney tissues were examined by light and electron microscopy. Rats receiving gentamicin demonstrated progressive renal proximal tubular necrosis which was nearly universal at the end of 10 days. Their BUN and creatinine levels rose progressively over the same period. Even at the higher dosage, tobramycin therapy resulted in only rare foci of proximal tubular necrosis and minimal elevation of BUN and creatinine. Although they occurred later and were substantially less severe, the ultrastructural changes induced by tobramycin were the same as those seen following gentamicin administration. These results indicate that the mechanism of tobramycin-induced renal injury is probably similar to that of gentamicin and that tobramycin is significantly less nephrotoxic in this experimental model.

Animals

Application of an in-vitro perifusion technique to studies of luteinizing hormone release by rat anterior hemi-pituitaries: Self-potentiation by luteinizing hormone releasing hormone.

A technique is described for the continuous perifusion of rat adenophypophyses. Exposure of the perifused glands to repeated equal 5 min stimuli with hypothalamic extract resulted in a series of equal peaks of corticotrophin secretion, the response was proportional to log dose over the range 0 - 25-2 - 0 rat hypothalamic equivalents/ml. Repeated equal stimuli with hypothalamic extract, or with luteinizing hormone releasing hormone (LH-RH) at concentrations of 2 or 10 ng/ml, resulted in a progressively increasing series of peaks of LH secretion, i.e. a self-potentiating or priming effect. The effect took between 30 min and 1 h to develop. A delayed increase in the responsiveness of the glands was also seen with continuous incubation of anterior pituitaries with LH-RH. The relevance of these observations to the physiological control of LH secretion is discussed.

Adrenocorticotropic Hormone