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Biomedical subjects

C Martinez

Publications and source records attributed to C Martinez.

At least 217 records · Page 12Linked to original sources

Bovine skeletal muscle adenosine deaminase: kinetic and thermodynamic studies.

Adenosine deaminase from bovine skeletal muscle catalyzes the hydrolytic deamination of adenosine to inosine and ammonia via an ordered Uni-Bi mechanism, if water is not considered as a true second substrate, as deduced from the inhibition pattern products. The inhibition constants (Ki) obtained for inosine and ammonia were 316 mumol/l and 2 mol/l, respectively. The activation energy of the reaction has been calculated as 10 kcal/mol, delta H* and delta F* as 7.9 and 15.6 kcal/mol, respectively, and delta S* as -23 cal/mol/degrees K.

Adenosine Deaminase↗

Development of Ly-1+ B cells in immunodeficient CBA/N mice.

Spleen cells from CBA/N mice developing a systemic autoimmune disease after daily injection of CsA during an autologous bone marrow reconstitution were transferred into unmanipulated syngeneic recipients. Adoptive transfer allowed the development of Ly-1+ B cells, which shared Mac-1 differentiation antigen expression with the myelomonocytic lineage. Interestingly, expansion of formerly absent Ly-1+ B cells was paralleled by a severe reduction in common, Ly-1-, B cell development in the recipient. We conclude that precursors for Ly-1+ B lineage do exist in CBA/N mice.

Animals↗

Interleukin 2 pathway is autonomously activated in human T11+3-4-6-8- thymocytes.

Mitogenic membrane ligands have been shown to activate interleukin 2 (IL2) production only in mature T cells, IL2 constitutive secretion having not yet been demonstrated. Here we have isolated a population of T11+3-4-6-8- human thymocytes and CD7+/T11-3-4-6-8- prothymocytes which produce and consume IL2 upon phytohemagglutinin triggering. Interestingly, their proliferation in the absence of any exogenous stimulating agent was related to an autonomous use of the IL2 system (IL2 secretion and binding to its specific receptor, whose constitutive, functional expression in human early thymocytes was recently shown). The internal activation of this system before T cell receptor acquisition stresses the relevance of the understanding of the alternative activation pathway(s) in T cell development. These findings, together with the demonstration of IL2-promoted differentiation of human early thymocytes into mature T cells, suggest that IL2 may also be a growth and differentiation factor acting specifically early in T cell development.

Antigens, Differentiation, T-Lymphocyte↗

A functional idiotypic network of T helper cells and antibodies, limited to the compartment of "naturally" activated lymphocytes in normal mice.

As shown previously, idiotype (Id) sharing between anti-2,4,6-trinitrophenyl T helper (Th) cells and antibodies in BALB/c mice results from immunoglobulin (Ig)-dependent selection of the T cell repertoire. In contrast, a clonotype defined by the same F6(51) anti-Id antibody is expressed by C57BL/6 anti-(4-hydroxy-3-nitrophenyl)acetyl Th cells independently of Ig influences. We have now used these systems to test the hypothesis that Ig-dependent Th cell repertoire selection occurs in the compartment of "naturally" activated lymphocytes. "Naturally" activated or resting splenic L3T4+ cells were separated from normal BALB/c and C57BL/6 mice and tested, either directly or after in vitro priming, in hapten-specific helper assays for expression of the clonotope defined by the F6(51) anti-Id antibody. The results show the selective expression of the antibody-dependent T cell Id in the "naturally" activated helper cell compartment. In contrast, when the T cell Id is expressed in the absence of Ig-dependent selection, it is only detected in the resting helper cell repertoire. Furthermore, BALB/c "natural" IgM antibodies with anti-Id specificities similar to F6(51) show functionally relevant interactions with syngeneic "naturally" activated Th cells. These are also characterized by high paratopic/Id degeneracy, as compared to helper cells obtained by conventional immunization. These results demonstrate repertoire differences between the set of (resting) lymphocytes participating in immune responses, vs. those "internally" activated in normal individuals. They also suggest the importance of Id network interactions in the compartment of "naturally" activated T and B cells.

Animals↗

A common idiotope on T cell receptors and antibodies expressed in the absence of network selection.

The monoclonal antibody F6(51), directed to an idiotope of MOPC 460-like anti-1,4,6-trinitrophenl (TNP) antibodies produced in IgHa mouse strains, identifies in helper T cells from C57BL/6 (IgHb) mice with (4-hydroxy-3-nitrophenyl)acetyl (NP)-self specificity, a clonotypic determinant functionally and biochemically associated with the specific T cell receptor. The expression of this antibody-related T cell clonotype in C57BL/6 mice, although "recurrent", is independent of network selection, as shown by its presence in B mice suppressed from birth with anti-mu antibodies, and in IgH-congenic mouse strains. These results indicate aleatory cross-reactivity between T cell receptors and antibodies and command caution in network interpretations for "idiotype sharing".

Animals↗

Prevalence of anti-Legionella pneumophila antibodies in various groups with different risk factors in Seville (Spain).

A study was undertaken to establish the background prevalence of antibodies to L. pneumophila in 324 persons from the area of Seville, Spain. The serum specimens were obtained from healthy volunteers divided into groups with different risk factors. The results were as follows: a prevalence of 1.96% in 51 persons working in a cooling-tower air conditioned building (group A), a prevalence of 25% in 36 persons working in a dry-heat air conditioned building (group B), a prevalence of 16% in 87 underground construction workers (group C) and a prevalence of 1.2% in 150 healthy blood donors with none of the above risk factors (group D). There is statistical significance between D and B and C.

Adolescent↗

Sporadic idiotypic cross-reactivities between antibodies and T helper cells: one example of aleatory expression of T cell idiotypes.

Idiotypic cross-reactivities between T and B cell receptors have been taken in the past to suggest VH-gene expression by both types of lymphocytes. More recently, after the molecular characterization of TcR, those observations were reinterpreted to indicate idiotypic network regulation, operating to select cross-reactive idiotypes in both B and T cell compartments. In support of these views, it has been shown that T cell expression of idiotypes is controlled by IgH-linked genes and markedly altered in B cell-deprived mice, and that T cells "learn" idiotype expression from the B cell compartment in the first few weeks of life. In most of these studies, aleatory idiotype cross-reactivities have not been sufficiently considered. Given the large diversity of antibodies and TcR, and the degeneracy of antibody-ligand interactions, it could be expected that a (monoclonal) anti-idiotypic reagent prepared against an antibody idiotope will always "cross-react" with some TcR variable regions. If these will be "major" T cell clonotypes, situations of idiotype sharing by B and T cells can be found which indicate neither VH-gene expression by T cells nor idiotypic network regulation. We report here one example of such aleatory expression of antibody idiotypes by T lymphocytes. A monoclonal anti-idiotypic antibody directed to anti-TNP antibodies of BALB/c mice specifically inhibits the growth and effector activity of C57BL/6 anti-NP-self helper T cells, while failing to interact with either BALB/c anti-NP-self or C57BL/6 anti-TNP-self helper cells. The clonotypic nature of these interactions could also be demonstrated by the specific induction of IL-2 production in the appropriate helper T cells by the anti-idiotypic antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Maternal transmission of idiotypic network interactions selecting available T cell repertoires.

Up to 75% of 2,4,6-Trinitrophenyl (TNP)-self-specific helper T cells from normal BALB/c mice share a clonotypic determinant with the anti-TNP myeloma protein MOPC 460, recognized by the monoclonal antibody F6(51). Immunization of adult BALB/c mice with the MOPC 460 idiotype (Ab2 mice) leads to high titers of circulating anti-idiotypic antibodies but has no influence on the expression of the T cell clonotype. In contrast, TNP-self-specific helper cells prepared in progenies from Ab2 females, or in BALB/c mice treated as neonatals with anti-idiotypic antibodies, fail to express the corresponding T cell clonotype when immunized as adults. These results demonstrate the idiotype-dependent selection of T cell repertoires early in life and their stability in adults.

Animals↗

A role for T3+4-6-8- transitional thymocytes in the differentiation of mature and functional T cells from human prothymocytes.

In vivo, immunocompetent T lymphocytes are only detected late in ontogeny, among mature thymocytes expressing either T4 (L3T4 in mouse) or T8 (Lyt-2) surface glycoproteins. We have previously shown, however, that there are functional precursors among T3+4-6-8- human thymocytes in vivo. Here we report on the in vitro differentiation of prothymocytes into T3+4-6-8- and mature T cells. T11+3-4-6-8- prothymocytes (0.5% of total thymocytes, greater than 98% pure) were obtained after treatment of thymocytes with OKT3 (T3), OKT4A (T4), Na1/34 (T6), and B9.4 (T8) monoclonal antibodies plus complement. During culture, the prothymocyte precursors acquire first T3 and then either T4 or T8, but not T6. The largest subpopulation in the thymus, T4+6+8+ cells, are not detected among the in vitro T-cell precursors. During culture, the precursors acquire cytolytic activity as soon as they express either the T3+4-6-8- or the mature (T3+4+8- or T3+4-8+) phenotypes. We suggest that T3+4-6-8- cells are a productive, transitional stage in T-lymphocyte development.

Antigens, Differentiation, T-Lymphocyte↗

Inhibition of monoamine oxidase by viloxazine in rats.

Biochemical and pharmacological investigations about the effect of the antidepressant drug viloxazine (Vivalan) on catecholamine metabolism in rats led to the following results: Viloxazine exerts a dose and time dependent inhibition of monoamine oxidase activity of brain and liver mitochondrial fraction and tissue homogenates of hypothalamus, heart, liver, and adrenal glands, both in vitro and after oral and parenteral administration in vivo. Consequently, an increase in catecholamine concentrations in brain of rats could be observed after pretreatment with viloxazine. In addition brain serotonin concentrations rose and 5-hydroxy-indoleacetic acid was diminished. However, characterization of inhibition of monoamine oxidase activity by viloxazine in vitro revealed: Compared to the specific inhibitors clorgyline for MAO-A- and pargyline for MAO-B-activity, viloxazine was a very weak inhibitor both for MAO-A and MAO-B in vitro. The type of inhibition was competitive and reversible. From the presented results and the results obtained by other laboratories it is concluded that inhibition of monoamine oxidase activity by viloxazine, although clearly demonstrated in animal experiments, may not be the only mechanism for an antidepressant action of the drug in man.

Animals↗