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Biomedical subjects

C Martínez

Publications and source records attributed to C Martínez.

At least 19 recordsLinked to original sources
PubMed1992

Hair zinc and dietary zinc intake during pregnancy and puerperium.

A longitudinal study of hair zinc concentration was carried out in 36 pregnant women at 12 and 36 weeks of gestation and 40 days postpartum. A progressive decrease in hair zinc concentration was noted through pregnancy; the decline between 12 and 36 weeks of gestation was statistically significant (P < 0.005) remaining without significant changes in the postpartum. Nutrient intakes were calculated from 3-day weighed food records at the same periods and at 20 weeks of gestation. Zinc, energy and protein intakes decreased during pregnancy. Mean zinc intake at 20 and 36 weeks of gestation was about 66% of the recommended dietary allowance (RDA) (9.8 and 10 mg, respectively) and about 52% of the RDA in the postpartum (9.8 mg). Although hair zinc levels do decline in pregnancy and zinc intake was lower than RDA, the study revealed that zinc nutriture was adequate for normal growth and development of fetus.

Adult↗
PubMed1992

Homeoboxes in flatworms.

A search for homeobox-containing genes was done in the genome of a primitive metazoan, the parasitic tapeworm Echinococcus granulosus. Five different homeoboxes were isolated, none of them belonging to the classical Antennapedia-type. Three of the homeodomains are similar to those from the Drosophila melanogaster NK-type genes. The fourth homeodomain shares extensive identity with that of the recently reported homeobox-containing gene goosecoid from Xenopus laevis. The third helix (the recognition helix) of the fifth isolated homeodomain is identical to that of the Xlim-1 gene of X. laevis and the lin11 gene of Caenorharbditis elegans. Using PCR, some Antennapedia-type homeoboxes were cloned from the genome of two other Platyhelminthes, Dugesia tigrina (planaria) and Fasciola hepatica. These data suggest that, contrary to what is found for the majority of the more complex metazoans, Platyhelminthes contain few homeobox genes belonging to the Antennapedia-type.

Amino Acid Sequence↗
PubMed1992

Expansion and clonal deletion of peripheral T cells induced by bacterial superantigen is independent of the interleukin-2 pathway.

Injection of the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) into mice provokes a rapid expansion and subsequent contraction of the pool of SEB-reactive T cells bearing T cell receptor (TcR) V beta 8 gene products. Given that interleukin 2 (IL-2) stimulates proliferation, abolishes anergy, and counteracts apoptotic cell death in T cells in vitro, we tested whether the IL-2 synthesis inhibitor cyclosporin A (CsA) or a vaccinia virus recombinant releasing high amounts of human IL-2 modulate SEB responses in vivo. Surprisingly, neither IL-2 nor CsA were able to change the in vivo kinetics and magnitude of SEB-induced expansion, unresponsiveness to SEB, and peripheral clonal deletion of T cells expressing products of the SEB-reactive TcR V beta 8 gene family. In accord with these in vivo observations, IL-2 is incapable of reversing "anergy" and apoptotic cell death of V beta 8+ SEB-reactive T cells isolated from SEB-primed mice in vitro. Accordingly, upon SEB injection V beta 8+ T cells expand rapidly, without expressing IL-2 receptor (IL-2R)alpha chains in vivo, although SEB induces IL-2R alpha in vitro. Altogether, these results indicate that the IL-2/IL-2R-mediated pathway is not involved in T cell repertoire modulation by bacterial superantigens. Moreover, the data suggest that unresponsiveness of V beta 8+ T cells from SEB-primed mice is not a reversible process, but involves an unreversible commitment to programmed cell death. Absence or presence of IL-2 responsiveness could be a hallmark to distinguish truly reversible anergy and peripheral clonal deletion.

Animals↗
PubMed1992

lpr T cells vaccinate against lupus in MRL/lpr mice.

MRL/MP-lpr/lpr mice are homozygous for the lpr mutation that results in the accumulation of phenotypically abnormal cells (CD3+CD4+CD8-) in all lymphoid issues. Although no major abnormalities in the T cell receptor repertoire expressed by such lpr cells have been reported, the lpr mutation is a major disease-accelerating factor. Finally, intravenous administration of irradiated lpr cells recovered from the hyperplastic lymph nodes of adult diseased animals to young MRL/Mp-lpr/lpr mice resulted in a highly significant amelioration of disease parameters. This "T cell vaccination" approach resulted in a selective depletion of cells expressing products of the V beta 8.2 subfamily among lymph node T cells, in addition to eliciting a surge in peripheral T cells capable of conferring disease protection in adoptive transfer experiments. Thus, a strategy aimed at specifically reducing the frequency of lpr cells proved successful in mitigating the autoimmune process. These findings add to the involvement of lpr cells in the autoimmune process and constitute the first report that T cell vaccination may be beneficial to a spontaneously occurring autoimmune disease.

Animals↗
PubMed1992

Attenuation of autoimmune disease and lymphocyte accumulation in MRL/lpr mice by treatment with anti-V beta 8 antibodies.

MRL-MP-lpr/lpr mice are afflicted by a severe systemic autoimmune disease that is aggravated by the lpr mutation resulting in the accumulation of phenotypically abnormal lpr cells (CD3+CD4-CD8-) in all lymphoid issues including hyperplastic lymph nodes. Given that products of the T cell receptor V beta 8 gene family are overrepresented among lpr cells, different schedules aimed at selectively decreasing the frequency of lpr cells were designed. First, continuous administration of the monoclonal antibody F23.1 (specific for V beta 8 products) resulted in a significant depletion of V beta 8+ cells and prevented the manifestation of lymph accumulation at the same time as it reduced the serological, clinical, and histopathological signs of autoimmune disease. Along the same line, administration of either F23.1 or two different anti-F23.1 anti-idiotypic antibodies to MRL/Mp-lpr/lpr mothers elicited, in the offspring, the production of antibodies sharing a recurrent idiotype with F23.1 and resulted in long-term amelioration of autoimmunity and lymphadenopathy. Thus, a strategy aimed at specifically reducing the frequency of a subset of lpr cells proved successful in mitigating the autoimmune process.

Animals↗
PubMed1992

In vivo administration of interleukin-2 turns on anergic self-reactive T cells and leads to autoimmune disease.

One major mechanism of self tolerance involves the deletion of T cell clones in the thymus. In athymic mice, tolerance to self antigens must be generated extrathymically. T cells with self-reactive receptors undergo either peripheral clonal deletion or become unresponsive (i.e. anergic). The unresponsive state of human and mouse T cell clones in vitro can be reversed by the addition of exogenous interleukin (IL)-2, thus transforming anergic T cells to an activated state. Here it is shown that the in vivo delivery of IL-2 to athymic BALB/c nu/nu mice abrogates the anergic state of self-reactive V beta 3+ and V beta 11+ T cells [which are normally deleted in the minor lymphocyte stimulatory (Mls)-1b-, I-E(+)-expressing euthymic counterparts]. Thus, V beta 3+ and V beta 11+ T cells from IL-2-treated nude mice proliferate in response to T cell receptor cross-linking and acquire effector functions as measured by their ability to deliver aid to B cells upon specific stimulation. This activation correlates with the development of autoimmune manifestations (DNA autoantibodies, rheumatoid factors, erythroleukopenia and minimal change nephritis) in these IL-2-treated mice.

Animals↗
PubMed1992

Effect of aging on the kinetic characteristics of the insulin receptor autophosphorylation in rat adipocytes.

The effect of aging on the insulin binding parameters and on the kinetic characteristics of the insulin receptor autophosphorylation in rat adipose tissue has been investigated. Using solubilized receptors from adipocyte plasma membranes, no significant differences were identified in either affinity or receptor number in adult vs old rats. Time courses for in vitro receptor phosphorylation revealed that both the initial rate of autophosphorylation and the maximal 32P incorporation were decreased by 40% in old (24-month) animals as compared to adult (3-month) control rats. The tyrosine phosphatase activity associated with the adipocyte plasma membranes does not account for the decreased kinase activity found in old rats. Insulin sensitivity (measured as the dose of insulin required for 50% maximal stimulation of kinase activity) was similar in both groups of rats. However, the kinase activity showed a decreased responsiveness to the hormone in the old rats. Double reciprocal plot analysis of receptor phosphorylation revealed that the Km for ATP was not modified. In contrast, the insulin-stimulated Vmax value was decreased by two-fold in 24-month-old rats. The decrease in Vmax does not appear to be related to an increased basal phosphorylation level on Ser/Thr residues of the C terminus of the receptor beta-subunit. Thus, we conclude that the reduced insulin receptor kinase activity in adipose tissue from old rats is due, at least in part, to a defect of the intrinsic kinase activity of the insulin receptor.

Adenosine Triphosphate↗
PubMed1992

Inability of IL-2 and IL-10 to counteract B cell clonal deletion.

The B cell antigen receptor (BCR) delivers inhibitory signals in nascent B cells leading to the establishment of tolerance via clonal deletion or clonal anergy depending upon the type of antigen to which the B cells are exposed. In previous work, it has been demonstrated that activated Th2 cells, as well as some recombinant lymphokines, prevent the inhibition of growth and subsequent cell death induced through the BCR in model B cell lymphomas. Herein, we extend this work to another Th2 lymphokine, IL-10, that in contrast to IL-4 does not interfere with the deletion promoted by IgM crosslinking. The effect of individual lymphokines has also begun to be analyzed in a transgenic model of B cell clonal deletion. To this end, we have administered a recombinant vaccinia virus producing human IL-2 to mice expressing an autoreactive H-2Kk,b-specific transgenic IgMk and found that IL-2 does not abrogate B cell deletion in vivo.

Animals↗
PubMed1992

Mechanisms of self tolerance.

The redundancy of biological systems minimizes the probability that isolated molecular and cellular defects entail deleterious consequences. This notion also applies to the establishment and maintenance of tolerance to self antigens. Thus, immune homeostasis is attributed to multiple distinct safety valves that are connected in series and intervene at defined control points of the life cycle of the developing lymphocyte to guarantee the physical elimination, functional inactivation, or regulated inhibition of self-reactive, potentially autoaggressive, B and T cells.

Animals↗
PubMed1992

Production of porcine parvovirus empty capsids with high immunogenic activity.

The VP2 gene of porcine parvovirus was cloned in the baculovirus system and expressed in insect cells. The resulting product was present in high yield. It self-assembled into particles which were structurally and antigenically indistinguishable from regular PPV capsids. A high degree of purity of the recombinant capsids was obtained by ammonium sulphate precipitation of cell lysates. These virus-like particles were used as antigen in the immunization of two pigs. The pigs elicited an immune response which, when assayed by standard serological techniques, was identical to that of a commercial vaccine. The amount of recombinant antigen needed in a vaccine dose was only 3 micrograms in a primary dose and 1.5 micrograms in the booster.

Animals↗
PubMed1992

Degradation of cellular mRNA during influenza virus infection: its possible role in protein synthesis shutoff.

The kinetics of cellular mRNA decay in influenza virus-infected cells have been studied by means of blot hybridization using as probes cloned cDNAs of alpha- and beta-actin, alpha- and beta-tubulin and vimentin. Both cellular mRNAs isolated from the cytoplasmic fractions as well as total cell mRNAs showed a rapid decay, with up to 50% concentration reductions at infection times at which influenza virus M1 mRNA was still not detectable. In contrast, these cellular mRNAs were stable in uninfected cells. To ascertain the possible role of mRNA degradation in the cellular protein synthesis shutoff, the kinetics of protein synthesis in infected cells were examined by two-dimensional gel electrophoresis of extracts pulse-labelled at several times after viral infection. The synthesis of the cellular proteins was reduced, showing kinetics paralleling those of mRNA decay. It is proposed that influenza virus infection induces the destabilization of mRNAs and that this mRNA degradation is, at least in part, responsible for cellular protein synthesis shutoff.

Actins↗
PubMed1992

The empty sella: results of treatment in 76 successive cases and high frequency of endocrine and neurological disturbances.

OBJECTIVE: We assessed the frequency of endocrine or neurological disturbances and the results of surgery in patients with empty sella, diagnosed with cisternography and/or computerized tomography scanning. DESIGN AND PATIENTS: Analysis of hospital records of 76 successive patients (73 primary, three secondary empty sella) from a single institution. MEASUREMENTS: Clinical and neuro-ophthalmological evaluation. Serum PRL, GH, TSH, LH, FSH, T4, T3 by radioimmunoassay. Diagnosis of empty sella with cisternography and/or computerized tomography scanning (n = 69), or discovered at surgery (n = 7). RESULTS: Patients with empty sella had: headache (69.7%), visual disturbances (34.2%), cerebrospinal fluid rhinorrhoea (11.8%), endocrine disturbances (51.4%, including hyperprolactinaemia, acromegaly, Cushing's syndrome). A pituitary tumour was discovered in two patients, in seven other ones it was suspected but not found at surgery. Transsphenoidal packing of empty sellas was done in 56 cases, with 7.1% post-operative complications. With surgery there was improvement of headache in 71%, of visual disturbances in 46%. Cerebrospinal fluid rhinorrhoea (discovered at surgery in four other patients) was not resolved by the first operation in six out of 13 patients. In 20 patients without surgery, headache improved in 64.6%. CONCLUSIONS: The empty sella is frequently associated with a variety of neurological and endocrine disturbances, which is contrary to conventional belief. Cerebrospinal fluid rhinorrhoea is not a rare complication and it may be difficult to treat. Some cases of empty sella may be due to partial pituitary apoplexy. Autoimmunity may have existed in other cases. Surgery may be useful in many patients, but a judicious selection is needed because it entails complications and non-operated patients may improve spontaneously.

Adolescent↗
PubMed1992

Recombinant vaccine for canine parvovirus in dogs.

VP2 is the major component of canine parvovirus (CPV) capsids. The VP2-coding gene was engineered to be expressed by a recombinant baculovirus under the control of the polyhedrin promoter. A transfer vector that contains the lacZ gene under the control of the p10 promoter was used in order to facilitate the selection of recombinants. The expressed VP2 was found to be structurally and immunologically indistinguishable from authentic VP2. The recombinant VP2 shows also the capability to self-assemble, forming viruslike particles similar in size and appearance to CPV virions. These viruslike particles have been used to immunize dogs in different doses and combinations of adjuvants, and the anti-CPV responses have been measured by enzyme-linked immunosorbent assay, monolayer protection assays, and an assay for the inhibition of hemagglutination. A dose of ca. 10 micrograms of VP2 was able to elicit a good protective response, higher than that obtained with a commercially available, inactivated vaccine. The results indicate that these viruslike particles can be used to protect dogs from CPV infection.

Animals↗
PubMed1992

Interleukin-2: a possible trigger for autoimmunity.

High doses of recombinant interleukin-2 (IL-2) may induce autoimmune lesions in patients receiving experimental cancer treatment. In most cases, the manifestation of autoaggression is transient and organ-specific, predominantly affecting the thyroid gland. Only a fraction of the patients are concerned; most individuals (around 90%) do not develop any signs of autoimmunity. Apparently, endogenously hyperproduced IL-2 may also be implicated in the pathogenesis of autoaggression, since active phases of such disparate autoimmune diseases, like multiple sclerosis and systemic lupus erythematosus, are accompanied by elevated IL-2 serum levels. Taking into account that immunological self-tolerance is maintained by several distinct mechanisms, we investigated whether IL-2 would interfere with clonal deletion or clonal anergy in vivo. In several experimental systems, IL-2 failed to abolish clonal deletion in the murine thymus or in the peripheral T-cell compartment. IL-2 did not affect the clonal deletion of self-reactive B cells in the bone marrow either. In contrast, IL-2 was found to be effective in abrogating clonal anergy of non-deleted self-specific T cells. Only in the presence of high frequencies of self-specific, potentially autoreactive T cells, IL-2 induces autoimmune lesions. Thus, IL-2 interferes with a mechanism of self-tolerance that guarantees the inactivation of T cells that for some reason have 'escaped' clonal deletion. If these data, obtained in the murine system, are extrapolated to man, then it may be stated that the T-cell repertoire of most individuals has been completely purged from self-reactive cells. Only in the presence of a non-deleted, anergic, potentially auto-reactive T-cell population, could organ-specific disease be induced by IL-2.

Animals↗
PubMed1992

Coevolution of hosts and microorganisms: an analysis of the involvement of cytokines in host-parasite interactions.

Parasites may employ particular strategies of eluding an immune response by taking advantage of those mechanisms that normally guarantee immunological self-tolerance. Much in the way as it occurs during the establishment of self-tolerance, live pathogens may induce clonal deletion, functional inactivation (anergy) and immunosuppression. At this latter level, it appears that certain pathogens produce immunosuppressive cytokine-like mediators or provoke the host to secrete cytokines that will compromise the anti-parasite immune response. It appears that immune responses that preferentially involve T helper 1 cells (secretors of interleukin-2-and interferon-gamma) tend to be protective, whereas T helper 2 cells (secretors of IL-4, IL-5, IL-6, and IL-10), a population that antagonizes T helper cells, mediate disease susceptibility and are involved in immunopathological reactions. Cytokines produced by T helper 2 cells mediate many symptoms of infection, including eosinophilia, mastocytosis, hyperimmunoglobulinemia, and elevated IgE levels. Administration of IL-2 and IFN-gamma has beneficial effects in many infections mediated by viruses, bacteria, and protozoa. The use of live vaccinia virus might be an avenue for the treatment of or the vaccination against infection. We have found that a vaccinia virus expressing the gene for human IL-2, though attenuated, precipitates autoimmune disease in immunodeficient, athymic mice. Thus, although T helper 1 cytokines may have desired immunostimulatory properties, they also may lead to unwarranted autoaggressive responses.

Animals↗
PubMed1992

Maternal leukocyte metabolism during pregnancy and puerperium, and its relation to fetal growth.

Changes of energy metabolism in maternal leukocytes were studied longitudinally in 33 normal term pregnancies at 12, 20 and 36 weeks of gestation and 40 days post partum. Nutrient intakes were calculated from 3-day weighed food records at the same periods. Women tended to decrease their mean dietary intakes of energy and of most nutrients from early to late pregnancy. Glucose-6-P dehydrogenase (G6P-DH), pyruvic kinase (PK) and adenylate kinase (AK) activities rose significantly after the 12th week of pregnancy, reaching maximal values at week 20. The following period up to week 36 showed a significant decrease that continued in the puerperium, when their values were lowest. Adenine nucleotide contents and protein/DNA ratio followed a different pattern. A significant increase was also observed from weeks 12 to 20, remaining without changes during the second half of gestation, and falling at puerperium. The PK and AK activities showed a positive correlation with energy intake at 36 weeks of gestation and AK activity was negatively correlated with folic acid intake in the middle of pregnancy. At week 20, PK activity showed a positive correlation with both head circumference and body mass index of the newborn. There was also a correlation between protein/DNA ratio and head circumference at the 36th week of gestation. These findings may suggest a relationship between the metabolism of maternal leukocytes, and fetal development in utero.

Adenine Nucleotides↗