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Biomedical subjects

A J Duarte

Publications and source records attributed to A J Duarte.

At least 55 records · Page 3Linked to original sources

Inhibitory effect of cimetidine on graft survival of allotransplanted rats submitted to an active-passive enhancement protocol.

The objective of the present study was to determine whether cimetidine, a type-2 histamine receptor antagonist, inhibits the immunological enhancement of allografted rats achieved by treatment with donor antigen plus anti-donor antibody. Groups of rats submitted to this active-passive enhancement protocol and treated ip with 30 (APEC 30; Group I; N = 4) or 60 (APEC 60; Group II; N = 8) mg/day cimetidine for 14 days had a significantly shorter graft survival (20.2 +/- 5.1 and 11.1 +/- 2.6 days, respectively) than the control group (animals submitted to the enhancement protocol and killed on day 72 after transplant when the graft was beating normally; APE; Group III; N = 6; P less than 0.05). On the other hand, these animals had a significantly longer graft survival than rats allotransplanted but not treated for enhancement (ALLO; Group V; N = 5; 8.2 +/- 0.8 days). The surgical control, consisting of isotransplanted animals, had a long-term survival (ISO; Group VI; N = 6; rats killed 120 days after transplant with the graft beating normally). Animals treated with cimetidine, but not submitted to the enhancement protocol (AC 60; Group IV, N = 4) had a significantly shorter graft survival (6.25 +/- 0.5) than the allotransplanted animals (Group V). These results indicate inhibition of the suppressor mechanisms which participate in this type of immunological enhancement.

Animals↗

Neonatal hepatitis and lymphocyte sensitization by placental transfer of propylthiouracil.

A female newborn whose mother was taking propylthiouracil (PTU) for Graves' disease, presented with transient thyrotoxicosis (serum triiodothyronine 1,710 ng/dl) and signs of acute hepatic injury. Jaundice and choluria were evident on her fourth day of life. Serum total bilirubin reached 14 mg/dl, with a direct fraction of 11 mg/dl. Serum alanine aminotransferase and aspartate aminotransferase showed moderate elevations (110 IU/l and 61.5 IU/l, respectively), as well as the alkaline phosphatase which increased to about twice the upper limit of normal. When incubated with PTU, the patient's cultured peripheral lymphocytes underwent transformation to more than twice the values found in 2 controls, with a stimulation index (SI) of 3.19, compared to SI of 1.45 and 1.15 for the controls, suggesting a hypersensitivity mechanism involved in the hepatic injury. Although about 20 cases of PTU induced hepatic damage were reported in the medical literature, this is, as far as we know, the first description of neonatal liver injury probably caused by placental transfer of this drug.

Alanine Transaminase↗

Kinetics of class II MHC expression on cytotoxic T cells generated by skin allograft.

In the present work the kinetics of class II MHC expression on OX8+ lymphocytes generated by skin allograft and its relationship to the lytic activity were studied. Mononuclear cells from the spleen of LEW (RT1(1) rats bearing BN (RT1n) skin graft for 3, 5 or 7 days were sorted out by sequential immune affinity using columns of Degalan-V26 beads treated with anti-rat or anti-mouse Ig. After depletion of B cells, T cells were precoated with W3/25 MoAb (anti-CD4 equivalent) and sorted out using an anti-mouse Ig column. The W3/25-/OX8+ cells (CD8 equivalent) were then coated with OX4 MoAb (anti-RT1.B) or murine A.TH anti-A.TL alloantiserum (anti I-E, cross-reacts with RT1.D) and were passed through a new anti-mouse Ig column in order to obtain the four subpopulations, RT1.B+, .B-, .D+ and .D-. Their specific lytic activity against BN Con A-stimulated cells increased from the 3rd to the 7th d after the skin graft. The lytic activity observed on the 3rd and 5th d was associated with all four subpopulations analyzed. In contrast, on the 7th d, the lytic activity was concentrated in the RT1.B+ subpopulation. These results, associated with the increase in the number of OX8+/RT1.B+ cells along with days after graft, suggest that RT1.B expression is not essential but is associated with the effectiveness of the cytotoxic activity. It is also possible that RT1.B expression is a marker of cytotoxic T-cell differentiation.

Animals↗

Comparative study of adjuvant induced arthritis in susceptible and resistant strains of rats. III. Analysis of lymphocyte subpopulations.

The subpopulations of lymphocytes (W3/25+ and OX8+) in the blood, spleen and lymph nodes were analyzed comparatively in rats susceptible (Holtzman) and resistant (Buffalo) to the development of adjuvant induced arthritis (AIA). In naive rats, it was found that the ratio (T helper/T suppressor) was significantly higher in Holtzman compared to Buffalo rats suggesting that the susceptible rats possess less suppressor cells than the resistant. Following induction of AIA (7 and 14 days) the ratio T helper/T suppressor was not significantly different in either strain. When the resistant strain was treated with 25 mg/kg of cyclophosphamide, the T suppressor cells were significantly reduced and this was followed by a strong potentiation of the AIA. Our data suggest that susceptibility to AIA is related to alterations in the T suppressor cell subset.

Animals↗

Glucocorticoid receptors in subpopulations of human lymphocytes defined by monoclonal antibodies.

Glucocorticoid receptors (GR) were investigated in subpopulations of lymphocytes identified by monoclonal antibodies. Purified T (OKT3+) and non-T lymphocyte subpopulations were isolated from human peripheral blood using Degalan bead columns coated with rabbit anti-human IgG. Purified subpopulations of OKT4+ and OKT8+ lymphocytes were obtained by coating the nonadherent population (T cells) from the first column with OKT4+ or OKT8+ and pouring it into a second Degalan column, coated with goat anti-mouse IgG. GR content and affinity were analyzed by a whole cell assay with [3H]dexamethasone as tracer. The numbers of GR in lymphocyte subpopulations (OKT3+ cells, non-T cells, OKT4+, and OKT8+ cells) were nearly equal. It is concluded that the differential effects of glucocorticoids on the circulatory kinetics of OKT4+ and OKT8+ cells probably are not related to differences in glucocorticoid receptors of these T-cell subpopulations.

Adult↗

Migration patterns of lymphocytes in untreated and immunologically manipulated recipients of organ allografts.

We have investigated the migration patterns of normal LEW rat splenic lymphocytes (SLs) radiolabeled in vitro with [2-3H]adenosine and adoptively transferred i.v. into LEW hosts bearing LBNF1 heterotopic cardiac allografts. Twenty-four hours after cell transfer, the animals were killed and the radioactivity of all lymphoid and nonlymphoid tissues measured in a beta counter. The following experimental groups were studied: group 1, untreated recipients acutely rejecting their grafts at 7 days after transplantation; group 2, actively and passively enhanced recipients bearing long-term surviving grafts, at 7, 14 to 18, and 25 days; group 3, cyclosporin A-treated recipients; and group 4, B rats, each bearing indefinitely surviving grafts, at 7 and 20 to 30 days. In group 1, 28% of recoverable activity was found in spleen and 22% in mesenteric and peripheral lymph nodes. In animals with well functioning grafts of groups 2 and 3, SLs accumulated in both organs equally (25 to 27%). In animals in group 4, SLs migrated primarily to lymph nodes (30%) and away from spleen (20%). Sequestration in nonlymphoid tissues of animals experiencing graft rejection was higher than those with prolonged or indefinitely surviving hearts. By using mouse anti-rat monoclonal antibodies, the quantitative relationship between T cell subpopulations in transferred cell suspensions and in lymphoid organs of grafted hosts was also assessed. Lymphocyte migration patterns are influenced dramatically by the immunological status of recipients of vascularized organ allografts.

Animals↗

Expression of T cell differentiation antigens and Ia on rat cytotoxic T lymphocytes.

Study of lymphocyte subsets has been facilitated by the detection of various surface markers that are related to distinct functions. We have explored the use of affinity methods for separation of large quantities (10(8)) of rat cells and used this technique to identify surface markers of cytotoxic T lymphocytes. Splenocytes from animals bearing skin allografts for 7 days were depleted of B cells and were separated into T cell subsets by using W3/25 and OX8 monoclonal antibodies, which mark two nonoverlapping populations of peripheral T cells. Our results demonstrate that the cytotoxic T cells are W3/25- and OX8+. They also bear minimal or no Ag-F alloantigen, a peripheral T cell marker, and they express Ia-like products analogous to those of the mouse I-A subregion but not of the I-E/C subregion.

Animals↗

Restoration of allograft responsiveness in B rats by interleukin 2 and/or adherent cells.

LEW X BN)F1 cardiac allografts survive 1 wk in unmodified LEW recipients (MST +/- SD = 8.3 +/- 1.2 days) but indefinitely (greater than 100 days) in B rats, produced by 750 R sublethal x-radiation 3 to 4 wk after adult thymectomy and reconstitution with syngeneic bone marrow cells from thymectomized thoracic duct-drained donors. Graft survival appears independent of blocking antibodies and is not mediated by suppressor cells or loss of graft immunogenicity. The unresponsive state is eventually reversed by adoptive transfer of 10(8) spleen cells from nonimmune (MST +/- SD = 27.5 +/- 4.7 days) or alloimmune (MST +/- SD = 21.5 +/- 1.9 days) syngeneic animals. In contrast, concomitant administration of 2 X 10(7) thioglycollate-stimulated peritoneal exudate adherent cells plus 10(8) alloimmune syngeneic spleen cells produced acute allograft rejection in 50% of B recipients within 10 to 12 days, while in every instance grafts underwent acute rejection (MST +/- SD = 10.0 +/- 1.4 days) in B recipients treated with interleukin 2 (IL 2) rich conditioned supernatant plus sensitized cells. In vitro studies revealed that adherent cells from B rats possessed less than 50% the capacity of adherent cells from normal animals either to support the Con A-stimulated uptake of 3H-thymidine by splenic T cells or to promote production of IL 2 by spleen cells depleted of adherent cells. Altered lymphocyte migration patterns in B recipients may also contribute to prolonged allograft survival secondary to adherent cell dysfunction.

Animals↗

Severe juvenile type paracoccidioidomycosis in an adult.

Paracoccidioidomycosis has recently been classified into juvenile (acute) and adult (chronic) forms. The latter affects middle-aged men and causes mucocutaneous lesions, while the more rare juvenile form affects the reticuloendothelial system of children and adults of both sexes under 30 years of age. It is not yet known, however, if the patient's age has a role in determining the immune response patterns to the fungus and the evolution to one form or the other. We present a 45-year-old man who presented with juvenile type disease characterized by intra-abdominal polyadenopathy forming a large epigastric mass. Immune evaluation showed high titres of anti-Paracoccidioides brasiliensis antibodies and an antigen-specific cellular immune defect. Treatment resulted in resolution of the clinical and immune abnormalities. His epidemiological background also suggested acute disease: he developed disease after moving from an urban to a rural endemic area. We suggest that acute or juvenile disease may occur in a previously healthy, susceptible individual when moving to an endemic area, at whatever age.

Adult↗

Paracoccidioidomycosis in a renal transplant recipient.

Paracoccidioidomycosis is a fungal infection rarely described in immunodeficient patients. We report a severe case of pulmonary paracoccidioidomycosis in a renal transplant recipient and demonstrate deficiencies of in vitro lymphocytic transformation assays, skin hypersensitivity tests, as well as low levels of antibodies to Paracoccidioides brasiliensis.

Adult↗

Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats.

The immunomodulatory effect of cimetidine (CIM), a histamine type-2 receptor antagonist, was evaluated in respect to the blastogenic response to Con A of Wistar Furth (WF) rats infected by the Y strain of Trypanosoma cruzi (T. cruzi). Enhancement of blastogenesis of normal splenocytes was observed at a concentration of 10(3) M. However, the splenocytes from infected animals responded to concentrations of CIM ranging from 10(-8) to 10(-3) M. The mitogenic response to Con A of cells from infected animals was restored in the presence of CIM. The results show that CIM modulates the "in vitro" proliferative response of cells from T. cruzi-infected rats and suggest an immunoregulatory role of histamine and/or of cells that express H2 receptors in this infection.

Animals↗

Prevalence of HTLV-I and HTLV-II infections among HIV-1-infected asymptomatic individuals in São Paulo, Brazil.

Human immunodeficiency virus (HIV-1)-infected subjects with acquired immunodeficiency syndrome (AIDS) are often infected with multiple pathogens. In particular, HTLV-I and HTLV-II infections have been found more frequently in AIDS patients than in asymptomatic individuals in Europe and Japan. We carried out a serosurvey among asymptomatic HIV-1-infected subjects in São Paulo, Brazil and compared our results with those of other investigators. In this study, we found HTLV infection in 1.5% of 266 asymptomatic and 14% of 28 AIDS patients. Epidemiological data obtained from patients pointed out the use of intravenous drugs as the principal risk factor for acquiring retroviruses. In conclusion, our results are in accordance with other studies done in Brazil and elsewhere where the principal risk group for HIV/HTLV-I/II coinfection was IDU.

Acquired Immunodeficiency Syndrome↗

IL-2 and IFN-gamma, but not IL-4 secretion by peripheral blood mononuclear cells (PBMC) are related to CD4+ T cells and clinical status in Brazilian HIV-1-infected subjects.

It has been reported that production of IL-2 and IFN-gamma, known as T-helper type 1 cytokines, by peripheral mononuclear cells (PBMC) decreases with progression of HIV infection. In contrast, IL-4 and IL-10 production, Th2 cytokine profile, increases with HIV disease progression. PBMC were evaluated from 55 HIV-infected subjects from Divisão de Imunologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, to "in vitro" cytokines production after 24 hours of stimulation with PHA. Low levels of IL-4 production in both HIV-infected patients and normal subjects, were detected. The patients with CD4+ T cell counts < 200 showed a significant decrease of IL-2 and IFN-gamma production compared to controls. Patients with higher counts of CD4+ T cells (either between 200-500 or > 500 cells/mm3) also showed decreased production of IL-2 that was not statistically significant. There was a correlation between IL-2 and IFN-gamma release with CD4+ T cells counts. HIV-1-infected individuals with CD4+ T cells > 500 cells/mm3 showed increased levels of IL-2 and IFN-gamma, than individuals with CD4+ T cells < 500 cells/mm3. In conclusion, we observed a decline of IL-2 and IFN-gamma production at advanced HIV disease. IL-4 production was not affected during HIV infection. Taken together, these findings suggest that the cytokine profile might be influenced by the HIV infection rather than the cause of disease progression.

Adult↗

Activity of natural killer cells during HIV-1 infection in Brazilian patients.

UNLABELLED: Natural killer cells are increasingly being considered an important component of innate resistance to viruses, but their role in HIV infection is controversial. Some investigators have found that natural killer cells do not confer a protective effect during the progression of HIV disease, whereas others have shown that natural killer cells may be protective and retard the progression of the disease, either through their lytic activity or by a chemokine-related suppression of HIV replication. In this study, we analyzed functional alterations in the activity of natural killer cells during HIV-1 infection using a natural killer cells activity assay with K562 cells as targets. RESULTS: Our results show that the activity of natural killer cells decreases only in the advanced phase of HIV infection and when high (40:1) effector cell-target cell ratios were used. The depression at this stage of the disease may be related to increased levels of some viral factors, such as gp120 or gag, that interfere with the binding capacity of natural killer cells, or to the decreased production of natural killer cells -activity-stimulating cytokines, such as IFN-a and IL-12, by monocytes, a subset of cells that are also affected in the late stage of HIV infection. The data suggest that decreased natural killer cells cell activity may contribute to the severe impairment of the immune system of patients in the late stages of HIV infection.

Adult↗