Biomedical subjects

E Fernandez-Cruz

Publications and source records attributed to E Fernandez-Cruz.

16 recordsLinked to original sources

PubMed2006

Unusual case presentations associated with the CD45 C77G polymorphism.

CD45, the leucocyte common antigen, is a haematopoietic cell specific tyrosine phosphatase. Human polymorphic CD45 variants are associated with autoimmune and infectious diseases and alter the phenotype and function of lymphocytes, establishing CD45 as an important regulator of immune function. Here we report four patients with diverse diseases with unusual clinical features. All four have the C77G polymorphism of CD45 exon 4, which alters the splicing and CD45RA/CD45R0 phenotype of lymphocytes. We suggest that C77G may be a contributing factor in these unusual cases.

Abscess↗

PubMed2006

IgG monitoring to identify the risk for development of infection in heart transplant recipients.

Infectious complication represents a significant source of morbidity and mortality in heart transplant recipients. To assess humoral immunity markers that can predict the development of infection, 38 consecutive recipients of heart transplants performed at a single center were prospectively studied. Induction therapy included daclizumab. Immunoglobulin (IgG, IgA, IgM) and complement factors (C3, C4, and factor B) were performed by nephelometry in peripheral blood samples obtained before transplantation, and 7 days and 1 month after transplantation. During a mean follow-up of 16.9 months, 13 patients had at least one episode of infection (34.2%). Eight of these were cytomegalovirus (CMV) infections treated with intravenous ganciclovir, 2 were bacterial pneumonia, 1 patient had bacterial septicemia, 1 patient had urinary tract infection, and 1 patient had pulmonary nocardiosis. No significant association was found between infection and age, sex, immunosuppression, CMV serostatus of donor and recipient, or treated rejection episodes. Pre-transplant IgG (below median value=1140 mg/dL; relative risk [RR] 3.69; 95% confidence interval [CI] 1.01-13.54; P=0.04) and post-transplant IgG levels at day 7 (below median value=679 mg/dL; RR 11.21; CI 1.04-89.48; P=0.022) were associated with an increase in the risk for developing infections. Early monitoring of immunoglobulin levels might help to identify the risk for developing infection in heart transplantation.

Cohort Studies↗

PubMed2005

Partial response to anti-CD20 monoclonal antibody treatment of severe immune thrombocytopenic purpura in a patient with common variable immunodeficiency.

Immune thrombocytopenic purpura (ITP), alone or in combination with autoimmune hemolytic anemia (Evans syndrome) and/or autoimmune neutropenia, is frequent in patients with common variable immunodeficiency (CVID). A 34-year-old man with CVID had long-standing unresponsive ITP. The patient had a 9-year history of CVID on substitutive therapy with intravenous immunoglobulin (IVIG). The clinical course of CVID was complicated with refractory fistulizing inflammatory bowel disease, nodular regenerative hyperplasia of the liver, splenomegaly, severe portal hypertension, and hypercatabolism of IgG. ITP was refractory to medical therapy, including different combinations of corticosteroids, high-dose IVIG, azathioprine, and vincristine. Splenectomy was not performed because of severe portal hypertension. He received a total five doses of rituximab, a monoclonal antibody directed against CD20 antigen, at a dose of 375 mg/m(2). After an initially slow response, his platelet count increased to more than 50,000/microL by the fourth week of infusion. Therapy was well tolerated, and B lymphocytes were effectively depleted from the peripheral blood. The patient was completely tapered off glucocorticoids and maintained platelets at above 40,000/microL. The patient has not taken immunosuppressive agents for 11 months. Early treatment with rituximab might be an option for patients with CVID and ITP that do not respond to other treatments or for patients for whom a splenectomy is contraindicated.

Adult↗

PubMed2004

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naïve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control.

AIDS Vaccines↗

PubMed2003

Macroamylasaemia, IgA hypergammaglobulinaemia and autoimmunity in a patient with Down syndrome and coeliac disease.

The association between macroamylasaemia and coeliac disease in Down syndrome with multiple autoimmune abnormalities has never been reported. A 40-year-old woman with a 15-year history of immunoglobulin A and immunoglobulin M hypergammaglobulinaemia, chronic diarrhoea, persistent mild aspartate aminotransferase (AST) elevation and anaemic syndrome was admitted to hospital because in the previous 3 months she had developed amenorrhoea, dizziness, alopecia, constipation, pallor and asthenia. Biochemical and immunological analyses showed macroamylasaemia. The patient presented clinical and intestinal histopathological features of coeliac disease. Immunological abnormalities included the presence of antigliadin, antiendomysium, antitransglutaminase, antinuclear, antismooth muscle and anti-SSA/Ro antibodies. Macroamylase resulted in a complex of amylase and immunoglobulin A. Later clinical follow-up of a gluten-free diet showed a transitory decrease in seric immunoglobulin A and macroamylase with persistent autoantibodies and AST elevation. An intestinal mucosal immune disorder could lead to coeliac disease and macroamylasaemia in a patient with Down syndrome presenting other immune alterations.

Adult↗

PubMed1997

Induction of adhesion/differentiation of human neuroblastoma cells by tumour necrosis factor-alpha requires the expression of an inducible nitric oxide synthase.

Neuroblastoma cell lines (SK-N-SH and SK-N-MC) were induced to differentiate, as detected by the expression of neurofilament proteins of 68 and 200 kDa, and to express adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule) after stimulation with tumour necrosis factor-alpha (TNF-alpha). This induction was accompanied by the arrest of cell growth. The induction of neuroblastoma adhesion by TNF-alpha could be inhibited by the nitric oxide synthase inhibitors, L-N-monomethyl arginine (L-NMMA) and L-N6-(1-imidoethyl)-lysine (highly specific for the inducible enzyme), but not by the inactive enantiomer D-NMMA. These results indicate that TNF-alpha induces the adhesion of neuroblastoma cells via nitric oxide. This was confirmed by the finding that the adhesion/differentiation of SK-N-SH and SK-N-MC cells can be directly induced by the addition of nitric oxide donors, sodium nitroprusside and S-nitroso-N-acetyl-penicillamine, into the culture medium. The isoform of the nitric oxide synthase induced in human neuroblastoma cells by TNF-alpha treatment was identified enzymatically as isoform II by Western blotting and by the polymerase chain reaction. Thus TNF-alpha induces the in vitro adhesion/differentiation of human neuroblastoma cells through nitric oxide synthesized by a calcium-independent inducible form of nitric oxide synthase, clearly indicating that isoform II of nitric oxide synthase can be expressed in human neuronal cell types.

Animals↗

PubMed1988

Progressive cellular immune impairment leading to development of AIDS: two-year prospective study of HIV infection in drug addicts.

We have studied immunological, serological and clinical abnormalities in 264 HIV-positive and HIV-negative drug abusers. Ninety percent of the 264 drug addicts (mean age 26 +/- 0.8 years) were found to have HIV antibodies and there was a significant increase (P less than 0.01) in the frequency of HIV antibody positivity with increasing duration of exposure to parenteral drug abuse. There was a very strong correlation between the progressive decline of the mean T4+ helper/inducer cells and T4+/T8+ ratio, the low response to pokeweed mitogen and the more severe clinical manifestations of HIV infection. Impairment of delayed-type hypersensitivity reaction to recall antigens was only seen in group IV as defined by the Center for Disease Control. Within group IV, anergy was found to be highly associated (83%) in patients with opportunistic infections. All other HIV-positive addicts from groups II and III, as well as HIV-negative addicts had normal in vivo responses to test antigens. We have also analysed in a prospective follow-up lasting 6-24 months, the evolution of HIV infection in a cohort of 50 HIV-antibody-positive drug addicts. Thirty-two percent showed clinical progression and most of the drug addicts that proceeded to full-blown AIDS developed anergy (82%) prior to clinical deterioration with development of opportunistic infections. We conclude, that in seropositive drug addicts a low absolute count of helper/inducer cells (mean +/- s.e. = 243 +/- 48 cells/mm3), a low response to pokeweed mitogen and anergy are predictive markers of progression to AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1985

In vivo activity of lymphokine-activated macrophages in host defense against neoplasia.

Purified splenic macrophage (M phi) from normal DBA/2J mice and mice bearing P815 tumors were examined for responsiveness to lymphokine (LK) preparations containing high concentrations of IFN-gamma. For both normal and tumor-bearing M phi, LK treatment induced morphologic changes and increased the percentage of Ia+ cells from 35 to 55%. Although neither population exhibited spontaneous cytotoxicity toward P815 targets, LK treatment induced considerable tumoricidal activity in tumor-bearing M phi (32 to 80% lysis) but only minimal activity in normal M phi (8 to 17% lysis). Subcutaneous injection of 1 X 10(6)P815 cells into DBA/2J led to progressive tumor growth and death of 100% of the recipients after 27 +/- 3 days. Injection of a 1:18 mixture of P815 with either LK-activated normal or tumor-bearing M phi caused tumor regression after 10 days, and prolonged life until 43 +/- 4 days with tumor-bearing M phi and 39 +/- 3 days with normal M phi. Untreated normal or tumor-bearing M phi were unable to cause the effect (30 +/- 2 days), and lymphocytes could not be substituted for M phi (25 +/- 3 days). In x-irradiated recipients, no effect of LK-activated M phi could be observed (control = 19 +/- 2 days; LK-activated tumor-bearing M phi = 21 +/- 3 days). In addition, administration of an admixture of LK-treated M phi and x-rayed tumor before challenge with viable P815 enabled the recipient to inhibit tumor growth and caused tumor necrosis with inflammatory cell infiltration of the tumor. These observations suggest that, in part, LK-activated M phi may interact in vivo with host-derived cellular components and enhance the immune reactivity of the host against the tumor.

Animals↗

PubMed1982

Altered levels of mononuclear leukocytes in tumor-bearing rats: decrease of helper T lymphocytes and increase of suppressor cells.

In the spleen and peripheral blood of BN rats with progressive tumors, W3/25+ T helper cells were significantly reduced and OX8+ T suppressor/cytotoxic cells were significantly increased. The ratio of helper to suppressor elements was decreased to 1.6 from a ratio of 3 in normal BN rats without tumors, and this decreased ratio correlated with tumor growth. When tumors were eliminated in vivo by infusion of effector cells (W3/25+ T lymphocytes), the levels of W3/25+ and OX8+ T cells returned to normal and the ratio of helper to suppressor/cytotoxic cells in the spleen and peripheral blood reverted to 3.0 or higher. Macrophages and null cells, T-sIg-, were also elevated in the spleen and peripheral blood of rats bearing expanding tumors and returned to normal levels after cure. Assays of spleen cells for cell-mediated cytotoxicity in rats with large tumors revealed little or no specific cytotoxicity. Cytotoxic activity was high in spleen of rats cured of their neoplasms by infusion of helper cells.

Animals↗

PubMed1982

Immunotherapy of a chemically-induced sarcoma in rats: characterization of the effector T cell subset and nature of suppression.

Chemically-induced sarcomas (BC5), established subcutaneously and growing progressively in BN rats, were completely eliminated by i.v. infusion of syngeneic effector cells. The effector cells were generated from BN spleen cells immune to BC5 in a mixed lymphocyte-tumor cell culture (MLTC). Generation of a high yield of effector cells that were efficacious in eliminating BC5 in vivo necessitated: depletion of macrophages from immune spleen populations, before preparation of MLTC; addition back to MLTC of a small number of macrophages from normal spleens to attain a level of 0.5% of the spleen cells in culture; and addition of T cell growth factor on day 5 of MLTC. With these conditions a subset of T cells was expanded. They were blast cells with surface markers W3/25 and Ia, which exhibited no cytotoxic activity in vitro, and probably functioned as a helper or amplifier element in the tumor-bearing host. Effector cells generated in MLTC with BC5, treated with mitomycin C, were specific for BC5 in vivo and did not affect growth of a viral-induced BN tumor.

Animals↗

PubMed1980

Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes.

Established subcutaneous Moloney sarcomas (MST-1) of large size and long duration were eliminated from syngeneic rats by intravenous infusion of varying numbers of specific syngeneic effector T lymphocytes. Spleen cells from BN rats in which tumor had regressed were cultured in an in vitro mixed lymphocyte tumor cell culture (MLTC) to augment cytotoxicity of effector cells. In the MLTC a T cell subset was expanded in response to MST-1 antigens and transformed into blast elements. With these changes, there was an increase in the W3/25 antigen on the T cell surface, a decrease of W3/13 antigen, and an increase in the number of T cells with Ia antigens. The subset associated with elimination of established tumors was a blast T cell W3/25+, W3/13+, as detected by monoclonal antibodies to rat T antigens. The W3/25+ subset was poorly cytotoxic in vitro for MST-1 and apparently functioned in vivo as an amplifier or helper cell in the tumor-bearing host. The W3/25- population was a melange of cells that included (W3/13+, W3/25-) T cells, null cells, Ig+ cells, and macrophages, and was associated with enhancement of tumor in vivo, suggesting the presence of suppressor cells.

Animals↗

PubMed1979

In vivo elimination by specific effector cells of an established syngeneic rat moloney virus-induced sarcoma.

BN rats immunized subcutaneously with a viral induced tumor (MST) or with a chemical-induced fibrosarcoma (BC5) were donors of immune spleen cells. Samples of immune spleen cells were tested in vitro against MST and BC5 in a 51Cr release assay before culturing and after 7 days of culture with mitomycin C-treated MST and/or BC5 tumor cells (MSTMit, BC5Mit). These spleen cells were infused in vivo i.v. into x-rayed (400 R) and nonirradiated BN recipients that bore a vascularized and progressive (1 to 1.5 cm in diameter) subcutaneous MST or BC5. Spleen cells from untreated BN donor rats were also tested in vitro and in vivo as controls. Established MST were specifically eliminated by spleen cells immune to MST after culture with MSTMit, but not by spleen cells immune to MST without further culture nor by cultured or uncultured BC5 immune spleen cells and control spleen cells. Also, the growth of BC5 was not affected by MST immune spleen cells cultured for 7 days with MST and/or BC5. Elimination of Moloney sarcoma (MST) in vivo occurred in less than 35 days and was correlated with the generation of cytotoxicity in vitro since only MST immune spleen cells cultured with MSTMit were able to augment significantly their cytotoxic capability in vitro.

Animals↗

PubMed1978

Hepatocyte damage induced by lymphocytes from patients with chronic liver diseases, as detected by LDH release.

We have used a cytoplasmic enzyme system in the study of the in vitro cytotoxic activity of human peripheral blood leucocytes against isolated liver cells in patients with chronic liver diseases. Lymphocytes from primary biliary cirrhosis and chronic active liver disease patients were shown to have an in vitro capacity to induce a cytolitic effect on isolated hepatocytes, as demonstrated by the enhanced release of lactate dehydrogenase (LDH), a cytoplasmic marker enzyme. No significant LDH release was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis. Our results corroborate, in a different assay system, by a simple, reproducible and different method, that lymphocyte-mediated liver cell damage "in vitro" occurs in both primary biliary cirrhosis and chronic active liver disease.

Animals↗

PubMed1976

Injurious effect on rat liver mitochondria by lymphocytes from patients with primary biliary cirrhosis.

Lymphocytes from primary biliary cirrhosis (PBC) patients were shown to have an injurious effect on rat liver mitochondria, as was demonstrated by the inhibition of mitochondrial respiratory control by these cells. The incubation of the PBC patients' lymphocytes with isolated rat liver mitochondria produced a significant inhibition of mitochondrial respiration in the presence of ADP. However, no significant effect on respiration was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis and miscellaneous liver diseases. The results suggest that this injurious effect of PBC lymphocytes on mitochondria might be a consequence of sensitization in vivo of the PBC patients' lymphocytes by the mitochondrial antigens.

Animals↗

PubMed1975

Mechanisms of destruction of human Rhesus sensitized red blood cells.

In order to determine the phagocytosis of human anti-D coated red cells we adopted a quantitative technique for its measurement using human erythrocytes labelled with 51Cr-chromate to support the assumption that erythrophagocytosis is one of the main mechanisms by which IgG-anti-D-antibody coated red cells are destroyed.

Chromates↗

PubMed1975

Impairment of mitochondrial respiratory control by activated lymphocytes.

Mitochondria isolated from rat livers were used as a source of antigens capable of producing in vitro activation of lymphocytes that had previously been sensitized in vivo with the same antigen. Such lymphocytes were shown to have an injurious effect on target mitochondria, as was demonstrated by a new biochemical approach based on the study of the inhibition by these cells of mitochondrial respiratory control. A somewhat milder injurious capacity was also observed in normal and sensitized lymphocytes activated in vitro with the mitogen PHA. The lateration of the respiratory control of mitochondria by lymphocytes correlated with an increase in DNA synthesis in these cells.

Adenosine Diphosphate↗