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Biomedical subjects

C Fernandez

Publications and source records attributed to C Fernandez.

At least 217 records · Page 12Linked to original sources

Immunological unresponsiveness to native dextran B512 in young animals of dextran high responder strains is due to lack of Ig receptors expression. Evidence for a nonrandom expression of V-genes.

Young mice of dextran high responder strains were found to be complete nonresponders to the alpha-1-6 epitope of dextran during 30-40 days after birth. They also failed to respond to thymus-dependent dextran-protein conjugates. Cells from young and adult mice were activated equally well to polyclonal antibody synthesis by the polyclonal B-cell-activating property of dextran. There was no age difference in the immune response to haptens conjugated to dextran, indicating that dextran can function as an efficient carrier also in young mice. Unresponsiveness could not be attributed to suppressor T cells or to a suppressive environment in young animals, as shown by transfer experiments, in which living or irradiated cells from young and adult mice were admixed in various ways and transferred to irradiated recipients of different ages. Cells from young mice did not affect response of adult cells (and the reverse), nor did the age of the irradiated recipient influence the response. When lymphocytes from young and adult mice were polyclonally activated in vitro by lipopolysaccharide, only cells from young mice failed to synthesize antibodies against the alpha-1-6 epitope of dextran, although they produced antibodies of all other specificities tested for. It was concluded that young animals fail to express immunoglobulins directed against the alpha-1-6 epitope during the first 30-40 days after birth. Since the mice possess the VH gene coding for antibodies against this particular epitope, it was concluded that the timing of V gene expression is regulated during development, possibly at the V-C gene translocation level.

Aging↗

Incidence of meningeal involvement by rhabdomyosarcoma of the head and neck in children: a report of the Intergroup Rhabdomyosarcoma Study (IRS).

141 patients with embryonal rhabdomyosarcoma (RMS) of the head and neck are reviewed. 57/141 had lesions of para-meningeal sites. 20/57 (35%) developed evidence of direct meningeal extension. 18/20 (90%) died of this complication. Radiation portals and doses were limited in 42% and 32%, respectively. All patients had chemotherapy for 6 weeks prior to radiation. The significance of the adequacy of radiation factors and the timing of chemotherapy are reviewed. Recommendations for managing these patients include earlier use of radiation and increased coverage of adjacent meninges by radiation including total craniospinal axis radiation when brain meningeal involvement exists.

Child↗

Composition and properties of the actinomycete flora in a ferralitic tropical soil (oxisol)-sugar cane ecological system.

Streptomycetes constituted about 46--48 per cent of the total aerobic microflora in the cultivated horizon of the studied ferralitic tropical soil below sugar cane plantation. This streptomycete fraction of the soil microbial community was composed of 13 (or more) species of Streptomyces (S. chromofuscus, S. chromogenus, S. diastatochromogenes, S. flavochromogenes, S. griseolus, S. nigrescens, S. phaeofaciens, S. sterilis, S. violaceus, Streptomyces sp. I--III), and Streptoverticillium (Sv. aspergilloides). None of these organisms did occur, with detectable frequency of occurrence, in the root surface region of sugar cane. Here, in the rhizoplane, we found a numerically small population of streptomycetes (about 5 per cent of the total bacterial flora), composed of two species (Streptomyces sp. IV and S. griseorubiginosus) which were, however, not detected in soil samples.

Cuba↗

Irreversible immunological tolerance to thymus-independent antigens is restricted to the clone of B cells having both Ig and PBA receptors for the tolerogen.

Mice were tolerized to the alpha1-6 epitope of native dextran. When their spleen cells were removed and activated by LPS, they did not synthesize antibodies against the tolerogen. However, when cells from tolerant mice were treated with dextranase or left untreated in culture for 24 h they were activated by LPS to the synthesis of antibodies against the tolerogen. When 24 h tolerized lymphocytes were treated with dextranase and transferred with immunogenic doses of dextran to irradiated mice they failed to produce antibodies against the tolerogen. In contrast, cells incubated with dextran for 2 h and thereafter dextranase treated were readily immunized by dextran in the same system. It is concluded that only the B cell clones having both Ig receptors and PBA receptors for the tolerogen become irreversibly tolerized, whereas B cells having Ig receptors for a different PBA are not tolerized, but remain in a resting state, even though their Ig receptors have bound the tolerogen.

Animals↗

Specific antibodies are responsible for the low dose suppression of the immune response to thymus-independent antigens.

Animals primed to the thymus-independent antigen native dextran B512 could not respond to the FITC hapten after immunization with native FITC-dextran. The degree of suppression of the anti-FITC response paralleled the increase of the anti-alpha1-6 PFC after priming with different doses of dextran. Suppression could be passively transferred with serum from dextran primed animals. Young animals that are very low-or non-responders to the alpha1-6 epitope of dextran B512, failed to suppress the anti FITC PFC response after priming with native dextran. We conclude that antibodies against the dextran carrier were responsible for the suppressed response to the FITC epitope in FITC-dextran immunized animals that had been primed with low doses of the dextran carrier.

Animals↗

Immunological tolerance to the thymus-independent antigen dextran can be abrogated by thymus-dependent dextran conjugates: evidence against clonal deletion as the mechanism of tolerance induction.

Tolerance to the alpha1--6 epitope of native dextran B512 was found to be very stable and could not be broken by the injection of dextran conjugated to several substances, such as protein A, keyhole limpet haemocyanin, edistin, concanvalin A or Staphylococcus bacteria, strain Cowan. However, when tolerant mice were injected with dextranase, all the above conjugates induced a strong anti-alpha1--6 immune response. In contrast, native dextran itself never induced a response in tolerant, dextranase-treated mice. It was concluded that tolerance only affects the specific B-cell subpopulation that can respond to the polyclonal B-cell-activating (PBA) property of dextran, whereas other specific B cells having PBA receptors for, e.g., signals delivered by collaborating T cells remain in a resting state. These B cells can respond in a specific immune response against the tolerogen after removal of the antigen, which blocks the Ig receptors and therefore prevents them from passively focusing the antigen. Thus, immunological tolerance is not caused by clonal elimination of the antigen-specific clone, but only affects a small subfraction of cells with Ig receptors against the tolerogen.

Animals↗

Microcin plasmids: a group of extrachromosomal elements coding for low-molecular-weight antibiotics in Escherichia coli.

Microcins are low-molecular-weight compounds produced and excreted by Enterobacteriaceae. They inhibit the growth of a wide spectrum of microorganisms. Microcin-synthesizing transconjugants were obtained in seven out of eight experiments of conjugational transfer between wild-type microcinogenic strains of Escherichia coli and E. coli strain BM21. The physical analysis of one of the transconjugant strains that has acquired the ability to produce microcin 17 showed the presence of extrachromosomal DNA as a plasmid (pRYC17) of molecular weight 36 X 10(6) (18.3-micron length), which is absent in the "microcincured" derivative strain. pRYC17 was incompatible with plasmids of the IncFII group. Other suspected plasmids containing the information for the synthesis of microcins have not been clearly classified. Strains producing microcins 93, 136, and 140 show a partial incompatibility with IncFIII group of plasmids.

Anti-Bacterial Agents↗

Immunological unresponsiveness to thymus-independent antigens: two fundamentally different genetic mechanisms of B-cell unresponsiveness to dextran.

The immune response of mice to the alpha-l-6 epitope of dextran (Dx) B512 was found to be under genetic control. The congenic mouse strains A, A.CA, A.SW, A.TH, and A.TL exhibited a specific defect in their response to alpha-l-6. Also strain CBA/N was unresponsive to alpha-1-6, but the mechanism of unresponsiveness was found to be different. Unresponsiveness to alpha-l-6 in congenic A strains was not due to suppressor cells. Although these strains failed to respond to the alpha-l-6 epitope, they responded strongly to the hapten Fluorescein isothiocyanate (FITC) conjugated to Dx, indicating that the Dx can function as an efficient carrier in these strains. Dx was a potent polyclonal B-cell activator in congenic A strains as well as in high responder strains. Polyclonally-activating concentrations of lipopolysaccharide (LPS) failed to induce the synthesis of anti-alpha- l-6 antibodies in congenic A strains, although antibodies of all other specificities studied were produced. However, in high responder strains, LPS induced the synthesis of anti-alpha-l-6 antibodies. It was concluded that congenic A strains do not express V genes coding for antibodies against alpha-l-6. In contrast, strain CBA/N failed to respond to both the alpha-l-6 and FITC epitope on Dx, whereas they could respond to FITC conjugated to horse erythrocytes. Dx induced a very small, if any, polyclonal antibody response in B cells from CBA/N mice or male CBA/N x DBA hybrids, whereas Dx was a very potent polyclonal B-cell activator in female hybrids. It is concluded that CBA/N mice are nonresponders to Dx or haptenated Dx, because the cell population that can respond to the polyclonal B-cell activating properties of Dx is severely depleted.

Animals↗

Induction of immunological tolerance requires that the B cells can respond to the polyclonal B-cell-activating properties of the thymus-independent antigens.

Mice were rendered specifically tolerant to the fluorescein isothiocyanatedextran (FITC) epitope by injection of FITC-dextran B512. Their spleen cells were removed at various times and cultivated in vitro with different polyclonal B-cell activators, such as lipopolysaccharide (LPS), purified protein derivative of tuberculin, and native dextran. LPS caused the appearance of high affinity anti-FITC plaque-forming cells to an equal extent with cells from untreated and tolerant animals, whereas native dextran failed to activate cells from tolerant mice, although it was a potent activator of normal cells. It was concluded that tolerance induction only affects those B cells that could respond to the polyclonal B-cell-activating properties of the tolerogen, but not other B cells having an identical set of Ig receptors directed against the tolerogen.

Animals↗

Effects of thyroid hormones on the evolution of monoamine oxidase activity in the brain and heart of the developing rat.

The evolution of monoamine oxidase (MAO) activity towards tryptamine has been studied from birth to 20 days post-natal in the brain and heart of male rats. Hyperthyroidism was induced by thyroxine injections and hypothyroidism by PTU administration. The results are expressed per unit of fresh weight and per unit of protein weight. Cardiac MAO is higher in the hyperthyroid animals than in controls as soon as 5 days following birth; the difference between the 2 groups increases until 20 days. The deficiency in thyroid hormones, on the other hand, was followed by a slight decrease in the cardiac enzyme, this decrease reflecting the general deficit in protein synthesis. Brain MAO is not affected by hyperthyroidism, but a clear deficit follows PTU administration. This deficit is significant beginning at 10 days and the difference between the 2 groups increases up to 20 days. The effects of PTU-induced hypothyroidism can be corrected by thyroxine injections. Except for the decrease in the level of cardiac enzyme in hypothyroid animals, all the effects on MAO activity are independent of the total protein content of both organs.

Animals↗

Immune response against two epitopes on the same thymus-independent polysaccharide carrier. 1. Role of epitope density in carrier-dependent immunity and tolerance.

Immunogenicity and tolerogenicity of two epitopes (alpha 1-6 and FITC) on the same dextran B 512 carrier were investigated. The following conclusions were made: (1) Both epitopes were thymus-independent and immunogenic and tolerogenic as well. (2) The marked dose differences between the two epitopes with regard to tolerance induction were found to be a consequence of the affinity and the heterogeneity of the responding B cells as well as the epitope density employed for detecting the PFC in a predictable way. (3) The alpha 1-6 response, in contrast to the anti-FITC response, was homogeneous and of low affinity and the number of precursor B cells was low. (4) Different mouse strains were found to be high-, low- or non-responders to alpha 1-6, but all the strains tested responded to the FITC epitope coupled to dextran. (5) Dextran and FITC-dextran were polyclonal B cell activators in the strains tested, irrespective of their ability to respond to the alpha 1-6 epitope. The findings indicate that epitope density and mol. wt of the immunogen as well as Ig receptor affinity for the epitope on the B cells are variables which markedly influence the binding of the immunogen to the specific B cells and therefore affect the delivery of the non-specific triggering signal.

Animals↗

[Clinical experiences with untreated homologous vein grafts in reconstruction of arteries (author's transl)].

50 transplantations of homologous vein grafts in reconstruction of arteries are reported on. Vein grafts were either transplanted immediately or used after deep freezing. This procedure has proved to be effective in the replacement of arteries during our observation period of four years. Results of homologous vein transplants are similar to those of autologous transplants.

Arterial Occlusive Diseases↗