Chagas disease in a recipient of cord blood transplantation.
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Biomedical subjects
Publications and source records attributed to M Linares.
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PURPOSE: B7 molecules are a family of proteins that co-stimulate T cells during immune activation. Normally the corneal epithelial cells (CEC) do not express these molecules on their cell surface. Toll-like receptors play an important role in the innate immune response to invading pathogens and recently have been demonstrated to be expressed on mice cornea. The objective of this study was to determine whether adenoviral infection induces B7 molecules and TLR9 on human CEC. METHODS: CEC were isolated from human corneas treated with dispase-II, and grown in the presence of supplemented hormonal epithelial medium until confluence. Then CEC were then infected with adenovirus 5 (Ad5) and cultured for different times. The CEC were then recovered and stained against human CD80, CD86, TLR-9 and cytokeratin. All cells were analyzed by flow cytometry. RESULTS: Ad5 infection of CEC induced the expression of B7 molecules and TLR-9 after 24 hours in culture, rising to maximum levels at 72 hours. B7 expression at 72 hours was as follows: CD80 expression on infected CEC was 62% (standard error [SE] 2.6) versus 3% (SE 1.2) on non-infected CEC (p<0.001); CD86 expression on infected CEC was 95% (SE 2.1) versus 5% (SE 1.2) on non-infected CEC (p<0.001). TLR-9 expression at 72 hours was 80% (SE 1.2) on infected CEC versus 5% (SE 1) on non-infected CEC (p<0.001). CONCLUSIONS: Ad5 infection induced the expression of B7 molecules and TLR-9 on CEC.
Abstract Shared ancestral variation and introgression complicates the reconstruction of phylogenetic relationships among closely related taxa. Here we use overall genomic compatibility as an alternative estimate of species relationships in a group where divergence is rapid and genetic exchange is common. Heliconius heurippa, a butterfly species endemic to Colombia, has a colour pattern genetically intermediate between H. cydno and H. melpomene: its hindwing is nearly indistinguishable from that of H. melpomene and its forewing band is an intermediate phenotype between both species. This observation has lead to the suggestion that the pattern of H. heurippa arose through hybridization. We present a genetic analysis of hybrid compatibility in crosses between the three taxa. Heliconius heurippa x H. cydno and female H. melpomene x male H. heurippa yield fertile and viable F1 hybrids, but male H. melpomene x female H. heurippa crosses yield sterile F1 females. In contrast, Haldane's rule has previously been detected between H. melpomene and H cydno in both directions. Therefore, H. heurippa is most closely related to H. cydno, with some evidence for introgression of genes from H. melpomene. The results are compatible with the hypothesis of a hybrid origin for H. heurippa. In addition, backcrosses using F1 hybrid males provide evidence for a large Z(X)-chromosome effect on sterility and for recessive autosomal sterility factors as predicted by Dominance Theory.
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We compare the historical demographies of two Müllerian comimetic butterfly species: Heliconius erato and Heliconius melpomene. These species show an extensive parallel geographic divergence in their aposematic wing phenotypes. Recent studies suggest that this coincident mosaic results from simultaneous demographic processes shaped by extrinsic forces over Pleistocene climate fluctuations. However, DNA sequence variation at two rapidly evolving unlinked nuclear loci, Mannose phosphate isomerase (Mpi) and Triose phosphate isomerase (Tpi), show that the comimetic species have quite different quaternary demographies. In H. erato, despite ongoing lineage sorting across the Andes, nuclear genealogical estimates showed little geographical structure, suggesting high historical gene flow. Coalescent-based demographic analysis revealed population growth since the Pliocene period. Although these patterns suggest vicariant population subdivision associated with the Andean orogeny, they are not consistent with hypotheses of Pleistocene population fragmentation facilitating allopatric wing phenotype radiation in H. erato. In contrast, nuclear genetic diversity, theta, in H. melpomene was reduced relative to its comimic and revealed three phylogeographical clades. The pattern of coalescent events within regional clades was most consistent with population growth in relatively isolated populations after a recent period of restricted population size. These different demographic histories suggest that the wing-pattern radiations were not coincident in the two species. Instead, larger effective population size (N(e)) in H. erato, together with profound population change in H. melpomene, supports an earlier hypothesis that H. erato diversified first as the model species of this remarkable mimetic association.
Hevein is an N-acetyl-D-glucosamine (GlcNAc) specific lectin that has been hypothesized to participate in the IgE-mediated allergic reactions in patients with latex allergy. In this work we assessed the specificity and biological effect of hevein purified from rubber latex on human leukocytes, using epifluorescence microscopy and flow cytometry. Purified human granulocytes were stimulated in vitro with hevein, and production of oxidative radicals was measured by reduction of nitroblue tetrazolium formazan. Histochemical staining and flow cytometry showed that hevein recognizes specifically monocytes (CD14+) and neutrophils (CD16+), but not lymphoid cells. Hevein induced oxidative response in purified granulocytes; this effect was 1.3-1.5-fold higher than the effect observed with the lectin WGA (wheat germ agglutinin), or other lectins with different sugar specificity. The induced reactions and cellular recognition by hevein were inhibited with GlcNAc and its oligomers; as well as by glycoproteins containing tri-and tetra-antennary N-glycosydically linked glycans. Our findings suggest that neutrophils are the main target for latex hevein; this lectin induces production of oxidative radicals, which seem to play an important role in tissue damage during latex allergy.
Recent studies, primarily in Drosophila, have greatly advanced our understanding of Haldane's rule, the tendency for hybrid sterility or inviability to affect primarily the heterogametic sex (Haldane 1922). Although dominance theory (Turelli and Orr 1995) has been proposed as a general explanation of Haldane's rule, this remains to be tested in female-heterogametic taxa, such as the Lepidoptera. Here we describe a novel example of Haldane's rule in Heliconius melpomene (Lepidoptera; Nymphalidae). Female F1 offspring are sterile when a male from French Guiana is crossed to a female from Panama, but fertile in the reciprocal cross. Male F1s are fertile in both directions. Similar female F1 sterility occurs in crosses between French Guiana and eastern Colombian populations. Backcrosses and linkage analysis show that sterility results from an interaction between gene(s) on the Z chromosome of the Guiana race with autosomal factors in the Panama genome. Large X (or Z) effects are commonly observed in Drosophila, but to our knowledge have not been previously demonstrated for hybrid sterility in Lepidoptera. Differences in the abundance of male versus female or Z-linked versus autosomal sterility factors cannot be ruled out in our crosses as causes of Haldane's rule. Nonetheless, the demonstration that recessive Z-linked loci cause hybrid sterility in a female heterogametic species supports the contention that dominance theory provides a general explanation of Haldane's rule (Turelli and Orr 2000).
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To our knowledge this is the first description of lumbosacral polyradiculopathy produced by herpes simplex virus (HSV) without coinfection by cytomegalovirus (CMV) in a patient with HIV infection. The acute lumbosacral polyradiculomyelitis (ALP) in patients with AIDS is a well defined nosologic entity and classically associated to CMV infection. However, this pathology can be due to others etiologies as toxoplasmosis, syphilis, lymphoma, tuberculosis, cryptococcus, varicella-zoster virus fVZV), Epstein-Barr virus (EBT) and HSV associated CMV. The case report was documented with findings in cerebrospinal fluid, magnetic resonance imaging and was confirmed by detection of HSV DNA by polymerase chain reaction. CMV DNA was not detected and no clinical features of CMV disease was seen. Therapy with foscarnet was successful. This drug without gancyclovir associated has rarely been employed in the treatment of ALP. We believe that foscarnet may be a valuable alternative therapy for cases of ALP of suspected acyclovir-resistant herpes virus infection.
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We have retrospectively analyzed a series of 19 patients with hepatitis C virus (HCV) infection and chronic thrombocytopenia not attributable to hypersplenism or to other causes. Antiplatelet antibodies were present in 81% of cases. Response to prednisone was observed in 6 of 7 patients and 1 of 3 patients responded to intravenous immunoglobulins. No case of reactivation of liver disease was observed during or after therapy. We consider that the possibility of an underlying mechanism should be evaluated in thrombocytopenic patients with HCV infection who do not present hypersplenism. These patients could benefit from steroid treatment.
BACKGROUND AND OBJECTIVE: bcl-2 oncoprotein plays a major physiological role in hemopoietic and non-hemopoietic cells by preventing apoptosis (programmed cell death). Disregulation of this process may be important in oncogenesis and the response to treatment of patients with different hematological malignancies. We have investigated the levels of bcl-2 expression in plasma cells from patients with reactive plasmacytosis (RP), monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM), correlating the bcl-2 expression and clinico-biological features in MM patients. DESIGN AND METHODS: The percentage of bcl-2 (+) plasma cells and levels of bcl-2 protein expression were investigated in 73 patients at diagnosis. Immunofluorescence and immunoenzymatic methods were applied using McAb against bcl-2 protein, and the intensity of protein expression was assessed by both the mean channel fluorescence intensity (MFI) and semiquantitative methods. To evaluate the intensity of bcl-2 expression in proliferating plasma cells, sequential double immunoenzymatic staining with McAb Ki-67 and bcl-2 was applied in 10 patients with MM. Correlations between bcl-2 expression and the clinico-biological features in MM patients were also studied. RESULTS: The proportion of bcl-2 (+) plasma cells was significantly higher in MGUS and MM than in RP (p < 0.001). The intensity of bcl-2 expression in plasma cells (assessed by MFI) was significantly different between all groups studied (p < 0.0001). RP showed lower expression than MGUS and MM patients. MM stage III patients demonstrated higher bcl-2 expression values than MGUS (p < 0.01). According to the proportion of plasma cells expressing Ki-67, patients with a proliferative index (Ki-67+) > 4% showed lower bcl-2 expression than patients with proliferative index < 4% (p < 0.05). Immunocytochemistry showed that plasma cells from RP had a lower intensity of bcl-2 expression than MM (p < 0.001), and double immunostaining Ki-67/bcl-2 demonstrated that the majority of proliferating plasma cells had weak bcl-2 expression. There was no correlation between bcl-2 expression and clinico-biological parameters, response to therapy or overall survival in MM patients. INTERPRETATION AND CONCLUSIONS: Globally, the number of bcl-2 (+) plasma cells and the intensity of protein expression in neoplastic gammopathies are significantly higher than in reactive plasmacytosis and bcl-2 levels tend to increase with disease stage. bcl-2 may be relevant to the pathogenesis of malignant gammopathies, prolonging the survival of plasma cells by preventing apoptosis and increasing the chance of acquiring additional gene defects. bcl-2 expression could also contribute to the resistance to chemotherapy observed in MM disease.
In spite of the advances attained in the diagnosis and early intervention with antibiotics, morbidity and mortality associated with sepsis caused by Gram-negative bacteria are high. The mediators responsible for the pathogenesis of the sepsis are components derived from the own bacteria (endotoxins) and from the cells of the immune response of the host (tumor necrosis factor and some interleukins). The treatment traditionally used in sepsis is mainly directed against microorganisms by the use of increasingly potent antibiotics. However, it is clear that antibiotics are not a definitive solution, since even when they cause bacterial death, they have no effects on endotoxin and may increase their liberation when cellular lysis occurs. New and successful treatments for sepsis have been tried since the 1980's, including the use of polyclonal and monoclonal antibodies of murine and human origin, directed against the lipid A of the endotoxin, as well as monoclonal antibodies against the tumor necrosis factor. Although these molecules are not completely efficient for the interruption of the chain of undesirable events provoked by the endotoxin, it is valid to accept the appearance of immunotherapies as an adjuvant treatment for a condition that threatens life.
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