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Biomedical subjects

J Merino

Publications and source records attributed to J Merino.

At least 145 records · Page 8Linked to original sources

The antibody response in mice to carrier-free synthetic polymers of Plasmodium falciparum circumsporozoite repetitive epitope is I-Ab-restricted: possible implications for malaria vaccines.

The immunogenicity of a novel synthetic peptide consisting of an average of 40 (Asn-Ala-Asn-Pro) repeats of the circumsporozoite protein of Plasmodium falciparum, (NANP)40, was studied in mice without using any carrier proteins. First, high titers of anti-(NANP)40 antibodies could be obtained after immunization of C57BL/6 mice. These antibodies also reacted with an extract of mosquitoes infected with P. falciparum sporozoites. C57BL/6 nu/nu mice did not produce antibodies against (NANP)40. Secondly, when 14 strains of mice with nine different H-2 haplotypes were immunized with (NANP)40 without carrier, only H-2b mice were found to produce anti-(NANP)40 antibodies, whereas all non-H-2b mice were consistently unresponsive. This response was demonstrated to be I-A-linked by using recombinant and mutant mice. I-Ab [B10.A(5R)] mice produced anti-(NANP)40 antibodies as well as H-2b inbred mice. B6CH-2bm12 I-Ab-mutant mice showed only a very low response. Third, the antibody response against (NANP)40 could be induced in nonresponder mice by immunization with the peptide coupled to a carrier protein. In view of the existence of such an exceptional H-2b restriction in the response to sporozoite synthetic peptides in mice, the triggering of peptide-specific T cell responses in humans receiving sporozoite malaria vaccines might be difficult to achieve.

Animals↗

Autoimmunity after induction of neonatal tolerance to alloantigens: role of B cell chimerism and F1 donor B cell activation.

BALB/c mice rendered tolerant by the neonatal injection of semiallogeneic (C57BL/6 X BALB/c)F1 spleen cells develop features of autoimmune disease. The possible mechanisms involved in autoantibody production, particularly anti-DNA antibodies, were investigated. In the first 5 wk, there was polyclonal B cell activation, as indicated by marked hypergammaglobulinemia, with a predominance of IgG1 and an increased production of antihapten antibodies. IgG1 anti-SSDNA and anti-DSDNA antibodies were detected with similar kinetics, but at higher titers than the anti-hapten antibodies. Also, there was a correlation between the effective induction of tolerance, as evaluated by the measurement of alloantigen-specific cytolytic T lymphocyte precursors, the persistence of B cell chimerism, and the production of anti-DNA antibodies. Anti-DNA antibodies were observed only in mice exhibiting a persistence of immunoglobulins bearing the donor's allotype. To determine the origin of anti-DNA antibodies, experiments were conducted whereby newborn BALB/c (Igh-1a) mice were injected with F1 cells from mice resulting from a crossing between Igh congenic BALB/c mice bearing the IgCHb allotype and conventional C57BL/6 mice (Igh-1b). All anti-DNA and anti-hapten antibodies exhibited the Igb allotype and thus were produced by the F1 donor B cells. The initial phase of tolerance induction was apparently associated with an allogeneic helper effect, because DNP-KLH-primed F1 donor cells transferred to newborn BALB/c could be stimulated after challenge with DNP-BGG. The triggering of persisting auto-reactive F1 donor B cells may reflect an activation by "incompletely" tolerant semiallogeneic T cells.

Animals↗

High out-put congestive heart failure as first manifestation of Osler-Weber-Rendu disease.

We present two cases of hemorrhagic hereditary telangiectasia (HHT) or Osler-Weber-Rendu disease which started as heart failure. Both had multiple arteriovenous fistulas, one of them in a rare localization in this disease, a lower extremity. We conclude stressing the importance of thinking of HHT in the presence of obscure heart failure or arteriovenous fistulas and of looking for internal fistulas when faced by a HHT.

Aged↗

Benign fibrous histiocytoma in Hodgkin's disease.

A case of benign fibrous histiocytoma in a patient with previous Hodgkin's disease is reported. Benign fibrous histiocytoma consists of a proliferation of benign histiocytes in addition to inflammatory cells and occasional Reed-Sternberg-like cells. Hodgkin's disease is considered a malignant disorder of the monocyte-histiocyte cell line but also includes benign inflammatory cells as part of its histological picture. The possibility that these two entities are biologically related is considered. The pathogenic relationship between both entities is discussed in the context of the immune dysregulation associated with Hodgkin's disease.

Histiocytoma, Benign Fibrous↗

Increased IgA-producing cells in the blood of patients with active Henoch-Schönlein purpura.

Peripheral blood lymphocytes (PBL) producing IgA, IgM, and IgG, both spontaneously and after pokeweed mitogen stimulation in cell culture, were determined by a protein A hemolytic plaque assay in 20 children with active Henoch-Schönlein purpura (HSP), 42 with inactive disease, 22 normal controls of the same ages, and 18 children with upper respiratory tract infections (URTI). The geometric mean of circulating IgA-producing cells in active HSP (1,016 X divided by 1.55 cells/10(6) PBL) was increased when compared with the group with inactive disease (P less than 0.001), normal controls (P less than 0.001), and children with URTI (542 X divided by 2.03 cells/10(6) PBL, P less than 0.05). The number of circulating IgM-producing cells was slightly increased in active HSP (260 X divided by 2.65 cells/10(6) PBL) and URTI (256 X divided by 3.16 cells/10(6) PBL). Both values were higher than those found in the group with inactive disease (113 X divided by 2.26 cells/10(6) PBL, P less than 0.01). There were no significant differences among the 4 groups in the number of circulating IgG-producing cells. The number of cells producing each type of immunoglobulin after in vitro stimulation with pokeweed mitogen was similar in patients with active HSP, normal controls, and the group with inactive disease. These data demonstrate a selective increase in the number of circulating IgA-producing cells only during disease activity, and add further support to a possible pathogenic role of this immunoglobulin in HSP.

Adolescent↗

Hemiplegia and peripheral gangrene secondary to large and medium size vessels involvement in C.R.E.S.T. syndrome.

A woman with CREST syndrome since the age of 35, had 11 and 13 years respectively after her disease onset, two episodes of CVA with residual right side hemiplegia. The angiography revealed segmented stenosis in the left common carotid, right subclavian and left renal arteries. At the age of 49 she developed gangrene of the right foot, requiring below the knee amputation. Pathological examination of the surgical specimen, showed extensive intimal fibrosis of the vessel walls in large and medium size arteries. Involvement of large and medium size arteries is infrequent in scleroderma. The case described illustrates this severe and unusual complication.

Arteries↗

Function of atrioventricular node conduction: hyperbolic model.

Twenty four patients were subjected to an electrophysiologic clinical procedure. The conventional extrastimulus test was applied to verify the relation between conduction time increase through the atrioventricular node of the extrastimulus beat (delta AH), and its preceding interval (A1A2). Following the least square root method the parameters of the hyperbolic model delta AH.A1A2 = m . delta AH + n were adjusted. The correlation coefficients obtained and tested in all cases were very high and significant. From this hyperbolic equation it was possible to determine the equations for the effective refractory period (ERPe = m) and functional refractory period (FRPe = ERPe + n). The theoretical values for refractoriness approached very closely those of the actually measured ERP and FRP, in all cases. This model proved to be, in respect to adjustments and especially in calculating refractory periods, at least as good as the exponential model proposed previously by other authors.

Adolescent↗