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Biomedical subjects

A Bustos

Publications and source records attributed to A Bustos.

10 recordsLinked to original sources

Evidence that a putative anti-idiotypic monoclonal antibody may actually be recognizing circulating immune complexes.

Murine monoclonal antibodies (mAb) reacting with affinity-purified antihistone antibodies (AHA) from serum of a patient with systemic lupus erythematosus (SLE) were obtained. One of them, 8B3, was initially considered to recognize idiotypic (Id) determinants in AHA since (a) it reacted with AHA but not with control IgG; (b) this reactivity could be inhibited using affinity-purified AHA, but not with control IgG or whole serum; (c) affinity-isolated 8B3+ antibodies showed antihistone activity and not other activities tested so far; (d) antihistone activity due to 8B3+, but not that of 8B3- from the same serum, could be fully inhibited by the presence of 8B3 mAb in the antihistone assay and (e) serum levels of 8B3 reactivity were higher than normal in SLE patients with AHA (56%), in contrast with SLE patients without AHA (6%). From these results it was deduced that 8B3 defined a cross-reactive Id shared by a subset of AHA in SLE patients. However, the present results suggest that (a) 8B3 mAb did not recognize AHA or Ig, but did recognize a 55 kDa histone-binding protein; (b) this 55 kDa protein was present free at low concentration in all human sera, but also associated with IgG in 8B3+ SLE sera and (c) these complexes are responsible for the false positive results in the antihistone assay as shown for DNA/anti-DNA complexes. Thus, mAbs recognizing the non-Ig moiety of circulating immune complexes may resemble anti-Id antibodies with features of the so-called epibodies. These immune complexes may be responsible for false positive results and caution should be exercised in the interpretation of results.

Animals

Immunobiochemical evidence for the loss of sperm specific histones during male pronucleus formation in monospermic zygotes of sea urchins.

To obtain information on the remodeling of sperm chromatin during male pronuclei formation, we have followed the sperm specific histones (SpH) that form the nucleosomal core by Western immunoblot analysis with polyclonal antibodies directed against the core SpH. The results obtained indicate that the complete set of SpH is absent from zygote chromatin at the beginning of the first S phase. The disappearance of SpH is not coincidental for the five histone classes: SpH4 and SpH3 are lost 5-15 min post insemination (p.i.), SpH2B and SpH2A disappear 20-40 min p.i., and SpH1 is progressively diminished up to 30 min p.i. This order of sperm chromatin remodeling is not affected by the inhibition of protein synthesis by emetine, indicating that the factor(s) responsible for SpH disappearance are present in unfertilized eggs. The lost SpH's are not replaced by newly synthesized CS variants, since the basic proteins synthesized de novo during male pronuclei formation are not incorporated into chromatin remaining in the cytoplasm. These newly synthesized proteins are different from the CS variants as judged by their electrophoretic migration.

Animals

Occurrence of antibodies to protease-treated histones in a patient with vasculitis.

We describe the presence of IgG antibodies reacting with histones previously treated with proteases in a patient with vasculitis. The patient's serum did not react with nontreated histones and when several enzymes were tested separately, only alpha-chymotrypsin reproduced the effect. Reactivity was directed against histone fraction H2B and no other autoantibody was found in the patient's serum. This could represent an autoantigen-driven response, histones hydrolyzed in vivo with proteases being the immunogenic stimulus. Diagnostic and pathogenic implications derived from the existence of such autoantibodies are discussed.

Adult

Inhibition of in vivo tumor growth by a monoclonal IgM antibody recognizing tumor cell surface carbohydrates.

We have shown previously that IgM from Ehrlich tumor (ET)-immunized mice, recognizing ET cell surface carbohydrates, protects control mice to a subsequent tumor challenge. The factors involved in such IgM-mediated protection were unknown, since it was independent of complement activation. Here, we have extended these in vivo studies by means of monoclonal IgM antibodies. Two of them (A10 and E1), strongly recognizing ET cells and with specificity to ET cell surface carbohydrates, were selected. The results show that A10 (but not E1 or unrelated IgM antibodies) is able to protect nonimmunized mice against ET growth. Protection by A10 was also seen by reducing 800-fold the initial dose; however, E1 was unsuccessful whatever the dose used. A10-mediated protection was observed in C3-defective mice (cobra venom factor treated) or in C5-deficient DBA/2, but not in silica-treated animals. Endotoxin removal did not affect the protection afforded by A10 while specific IgM depletion prevented any protective effect. In addition, the relationship between natural antibodies of IgM isotype recognizing ET cell surface carbohydrates and mouse strain resistance to this tumor is established. Similarly, this natural resistance seems to be complement independent but macrophage mediated. Therefore, these results indicate that some IgM molecules recognizing cell surface carbohydrates may participate in in vivo tumor suppression by a macrophage-dependent mechanism.

Animals

[Diazepam reversion with flumazenil. Gasometric and sympathetic-adrenal study].

We report the effects of flumazenil as reversion agent of the effects of diazepam at high doses as a part of short-duration general anesthesia. We have studied ten women in ASA I general condition who received anesthesia with fentanyl, 2.5 micrograms/kg-1, diazepam, 0.4 mg/kg-1 and O2/N2 at 60%. At the end of the operation, flumazenil, 0.2 mg, was administered. Hemodynamic, respiratory and adrenergic effects were evaluated. The degree of awareness and subjective feeling of the patient at awakening were also evaluated. After administration of flumazenil, awareness state was significantly higher (p less than 0.001) and it persisted during the duration of the study (120 minutes). Respiratory rate and pO2 increased significantly with administration of flumazenil (p less than 0.25 and p less than 0.01, respectively) and pCO2 decreased from 42.2 mmHg to 37.9 mmHg (p less than 0.05). Neither hemodynamic parameters nor plasma concentration of catecholamines changed significantly. As secondary effects attributable to flumazenil, four patients complained of nausea and one patient referred anxiety. We conclude that flumazenil allows to carry out anesthetic techniques with high doses of benzodiazepines even in short duration interventions with safety and without cardiocirculatory nor sympathetic-adrenal alterations.

Adrenal Glands