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Biomedical subjects

N F Mendes

Publications and source records attributed to N F Mendes.

At least 19 recordsLinked to original sources

Influence of cholecalciferol (vitamin D3) on the course of experimental systemic lupus erythematosus in F1 (NZBxW) mice.

The course of systemic lupus erythematosus (SLE), an autoimmune disease, is markedly affected by hormones such as estrogen and prolactin. It is well known that heavy exposure to sunlight has deleterious effects on SLE, triggering episodes of the disease. Classical explanations for this occurrence suggest that UV radiation damages DNA, which becomes immunogenic, or induces exposure of the Ro antigen in keratinocytes. In recent years, it has been shown that vitamin D3 has important effects on the immune system. Thus, we proposed an alternative hypothesis, suggesting that UV radiation, by promoting vitamin D3 synthesis, could be a factor aggravating the course of SLE after exposure to sunlight. To test this hypothesis, we injected F1(NZBxW) mice, which are prone to developing SLE, with vitamin D3, and we demonstrated a worsening of the histopathological findings in the kidney.

Animals

Quantitation of soluble E-receptor of T lymphocytes in serum from HIV-1 positive patients.

Human T lymphocytes carry a membrane receptor for sheep erythrocytes (E) related to the CD2 molecule. The E-receptor is found in a soluble from (Rs) in serum and can be quantitated by "rocket electrophoresis" using an anti-Rs serum obtained by immunizing sheep with autologous erythrocytes coated with Rs. Increased serum levels of Rs are found in patients with diseases associated with immunodepression. In the present study, 14 asymptomatic HIV-1 seropositive individuals were investigated regarding their Rs levels and delayed hypersensitivity skin tests every 3 months for a period of 35 months. All these patients progressed to AIDS in this period. Rs serum levels have also been quantitated in 14 normal individuals. The mean Rs values in normal individuals, asymptomatic, and AIDS patients were, respectively: 4.8 +/- 1.5 mm (SD), 9.6 +/- 1.9 mm (SD) and 11.3 +/- 2.4 mm (SD). An increase of Rs serum levels was observed when we compared normal individuals with CDC-II and CDC-IV clinical stage patients (P < 0.05, Mann-Whitney test) and CDC-II and CDC-IV patients, (P < 0.05, Wilcoxon test). We have observed a depressed delayed hypersensitivity response to ubiquitous antigens in CDC-IV patients. Our results indicate that Rs serum levels can be used as a progression marker in HIV infected patients.

Adult

Stored blood--an effective immunosuppressive method for transplantation of kidneys from unrelated donors. An 11-year follow-up.

Thirty-seven patients were submitted to kidney transplantation after transfusion at 2-week intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of panel reactive antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P < 0.05. The incidence and reversibility of rejection crises during the first 60 post-transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56% and 77%, respectively, for the treated group and 39.8% and 57.5% for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that transfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process without impairing the adequate functioning of the renal graft.

Adult

Effect of glucan on murine lupus evolution and on host resistance to Klebsiella pneumoniae.

Glucan is a polysaccharide from the yeast Saccharomyces cerevisiae that stimulates the mononuclear phagocytic system (MPS). NZB/NZW F1 mice were divided into two groups: one group received a subcutaneous injection of 0.5 mg glucan/animal for 1 week, and the other received the same dose for 3 months. No changes were observed in those animals submitted to short-term glucan treatment, whereas animals with active lupus and submitted to long-term glucan administration presented early death, with significant differences in accumulated mortality rates over 33-37 weeks, when compared to controls. No deaths were observed in lupus mice treated with glucan 24 hours before the induction of septic shock by Klebsiella pneumoniae, in contrast to mortality of 95.3% in the control group during the follow-up period of 12 days. We conclude that although glucan is able to exacerbate lupus activity, it enhances resistance to infection in lupus mice.

Animals

Evaluation of recent techniques for detection of red blood cell antibodies in sera of reference samples, patients, pregnant women, and blood donors.

The sensitivity of the low ionic strength solution antiglobulin test (LISS-AGT), polyethylene glycol antiglobulin test (PEG-AGT), low ionic strength solution solid-phase antiglobulin test (LISS-SPAT), gel low ionic strength solution antiglobulin test (GEL-LISS), and gel papain test (GEL-PAP) was compared in titration studies of 460 sera containing identified IgG alloantibodies. The GEL-PAP was 100% sensitive to detect Rh antibodies, whereas the PEG-AGT was the most sensitive to detect Kell, Duffy, Kidd, Ss, and rare blood group antibodies. The better performance of PEG-AGT was especially obvious with Kell, Duffy, and Ss antibodies (S = 100%). When the sensitivity of the LISS-AGT, PEG-AGT, GEL-LISS, and GEL-PAP was evaluated in different routines, the GEL-LISS showed to be more sensitive than PEG-AGT in the detection of clinically significant antibodies. These discrepant results showed that the performance of a technique may change when it is applied as a routine.

Blood Donors

HLA antigens and resistance to HIV.

The role of histocompatibility antigens in HIV infection has been investigated by several approaches. Thus the haplotype A1B8DR3 that is usually linked to autoimmune disorders seems to be associated with accelerated progression to AIDS. Cross-reactivity between MHC antigens and HIV-1 proteins is evident from alloimmunization experiments in mice and xenoimmunization of monkeys with human cells. Furthermore, recent reports suggest that some individuals with uncommon HLA antigens may be resistant to HIV infection. In addition to expressing cross-reacting antigens with HLA, HIV also exhibits substantial amounts of host beta-2 microglobulin and HLA-DR attached to its surface. Taken together, these data are stimulating new hypotheses relevant for AIDS pathogenesis. Based on alloimmunization, novel approaches have also been proposed in attempts to promote an effective immune response to HIV.

HIV Infections

Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan).

In a effect to prevent nosocomial pneumonia and sepsis, we treated patients with severe multiple trauma with an immunomodulator--beta 1-3 polyglucose (glucan). Forty-one patients with no infection at admission were stratified using Trauma Score and included in a randomized double-blind controlled trial. They were divided into a control group (n = 20) and a glucan group (n = 21). Pneumonia occurred in 11 of 20 patients in the control group and in two of 21 recipients of glucan (p < 0.01). Sepsis occurred in seven of 20 patients in the control group and in two of 21 patients treated with glucan (p < 0.05). Considering patients with pneumonia and sepsis, a decrease was observed in nosocomial infection from 65.0 to 14.4 percent (p < 0.001). The mortality rate related to infection was 30.0 percent in patients in the control group and 4.8 percent in the group treated with glucan (p < 0.05). The general mortality rate, cerebral deaths excluded, was 42.1 percent in the control group and 23.5 percent in the glucan group.

Adjuvants, Immunologic

Delayed hypersensitivity skin tests in prognosis of human immunodeficiency virus infection.

Delayed hypersensitivity skin tests (DHST) with recall antigens were investigated as prognostic markers in five different approaches. In the first study, 42 acquired immunodeficiency syndrome (AIDS) patients (IVb, IVcl, IVd, and IVe; MMWR 35:334-339, 1986) 26 AIDS-related complex (ARC) patients (IVa and IVc2), and 98 asymptomatic patients (II and III) were evaluated with candidin, tricophytin, PPD and streptokinase-streptodornase. In the second study, 10 patients (II and III) were evaluated sequentially with the same antigens. In the third, 45 patients with at least two positive skin tests ("reactors") were followed for one year and evaluated every 6 months with the same antigens. In the fourth, 16 "reactors" were followed and evaluated every 3 months with the same antigens. We measured the interval from the time at which patients first presented with only one or no positive DHST until the development of ARC or AIDS. In the last study, the correlation between absolute number of CD4+ lymphocytes and the number of DHST was studied in 151 patients. We found that the decrease in reactiveness to DHST correlated directly with the progression to AIDS, demonstrating the usefulness of this simple procedure as a valid prognostic marker.

AIDS-Related Complex

Molecular forms of soluble human T lymphocyte receptor for sheep erythrocytes in serum and saliva.

Using a specific serum anti-soluble T lymphocytes receptor for sheep erythrocytes (E) and SDS-PAGE, we detected radioactive bands of molecular weight 58,000 in immunoprecipitates of supernatant of heated human lymphocytes (SHL), in the supernatant of PHA stimulated lymphocyte cultures (SLC), normal human serum (NHS), and serum from cancer and uremia patients, labelled with 131I. By Sephadex G-200 chromatography, in addition to this fraction, we detected molecules of molecular weight higher than 150,000 which interact with the anti-soluble receptor serum (anti-RS), in serum from cancer and uremia patients. These molecules were detected in NHS or SHL after concentration or by prolonged exposure of SDS-PAGE with some labelled and immunoprecipitated SHL samples. The soluble receptors of molecular weights 58,000 (RS1) and more than 150,000 (RS2) were fully identical when analyzed by immunodiffusion with anti-RS serum. When submitted to immunoelectrophoresis, RS1 showed electrophoretic migration similar to that of albumin, while RS2 showed a pattern close to that of alpha 2-globulin. However, RS2 did not show antigenic relationship with IgM and was not an immune complex with IgG. Even though the presence of RS in human saliva has not yet been reported, molecules that interact with anti-RS serum have been detected in human saliva and are fully identical to molecules found in supernatant of heated human T lymphocytes and NHS. The RS molecules present in human saliva have a molecular weight and electrophoretic migration similar to those of RS1 from SLC and from human serum and have no antigenic relationship with human albumin.

Animals

Purification of soluble human T lymphocyte receptors for sheep erythrocytes.

Using a polyclonal heterologous anti-soluble E-receptor serum, we identified molecules of molecular weight circa 58,000 and 150,000. The soluble receptor molecule with molecular weight of approximately 58,000 (Rs1) was initially purified from supernatant of heated lymphocytes through chromatography on Sephadex G-200 and/or DEAE-cellulose. The soluble receptor molecule with molecular weight of approximately 150,000 (Rs2) is detected at high levels in the serum of patients with cancer and uremia. Rs1 and Rs2 present in serum from cancer patients were purified by chromatography on Sephadex G-200 and by affinity chromatography using anti-Rs1 IgG. 131I-labelled supernatant of heated lymphocytes binds to sheep erythrocytes and the elution and analysis of the molecules adsorbed showed bands of molecular weights approximately 58,000 and 150,000, confirming the receptor activity of these molecules.

Animals

Quantitation of the soluble E-receptor of human T lymphocytes by rocket electrophoresis in the serum of patients with lepromatous and tuberculoid leprosy.

Human T lymphocytes carry a membrane receptor for sheep erythrocytes (E) which is responsible for the well-known phenomenon of E-rosette formation. This receptor has been related to CD2 molecules; it is present in a soluble form (Rs) in normal serum and may play an immunoregulatory role. In this study we quantitated soluble E-receptor in serum samples of 43 normal controls, 32 patients with tuberculoid leprosy and 53 with lepromatous leprosy, using rocket electrophoresis and an anti E receptor serum (anti-Rs) obtained from an adult sheep immunized with autologous E treated with Rs. In the 3 groups studied, the rocket means were respectively 5.0, 7.5 and 10.9 mm (p less than 0.001). We found abnormally high levels of Rs in the serum of various diseases associated with a depression of cell-mediated immunity. The increase of Rs levels in the serum may be one of the mechanisms responsible for the depression of cellular immunity in leprosy.

Adult

Seroepidemiological studies of HIV-1 infection in large Brazilian cities.

The prevalence of HIV-1 antibodies in selected groups of individuals from Rio de Janeiro, São Paulo and Santos was determined retrospectively. These groups and respective prevalences were: hemophiliac patients from Rio de Janeiro (1983-1984) 98.0%; polytransfused hemodialysis patients from São Paulo (1985-1986) 3.0% and (1987) 7.7%; intravenous drug addicts from São Paulo and Rio de Janeiro (1986-1987) 15.9%; male prisoners from São Paulo (1988) 12.5%, and pregnant women from Santos (1988-1989) 3.6%. These data stress the magnitude of AIDS in Brazil.

Adolescent

Transfer of cell-mediated immunity to HIV antigens in vivo to a Cebus monkey and in vitro to human lymphocytes with xenogeneic immune RNA.

1. Immune RNA (iRNA) was extracted from the spleen of a sheep immunized with human immunodeficiency virus (HIV) antigens. 2. The transfer of cell-mediated immunity to HIV antigens was accomplished by injecting iRNA into a Cebus monkey, as evaluated in vitro by leukocyte migration inhibition. The in vitro treatment of normal human leukocytes with iRNA also promoted the inhibition of leukocyte migration in the presence of HIV antigens. 3. These findings have important theoretical and potential practical applications in the field of Acquired Immunodeficiency Syndrome (AIDS).

Animals

Comparison of the cell walls of Paracoccidioides loboi and Paracoccidioides brasiliensis by using polysaccharide-binding dyes.

Biopsies from patients with Jorge Lobo's disease (keloid blastomycosis) and paracoccidioidomycosis (South American blastomycosis), caused respectively by Paracoccidioides loboi a non-cultivated fungus and Paracoccidioides brasiliensis, were stained with six different dyes having the property of forming complexes with some polysaccharides and oligosaccharides. The cell-walls of both fungi showed similar staining characteristics, suggesting a similar chemical structure. The role of the fungal cell-walls in evasion mechanisms is discussed.

Cell Wall

HLA compatibility and graft survival in 502 kidney transplants.

The survival of 502 kidney grafts (458 first-grafts and 44 second-grafts) performed at Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, was analyzed in relation to the degree of HLA compatibility. The actuarial graft survival for first-transplants, at 1 and 5 years, was a follows: a) HLA-identical donor: 90 and 83%; b) one-haplotype identical donor: 68 and 54%; c) unrelated living donor: 61 and 37.5% and d) cadaver donor: 52.5 and 32%. These survival data are similar to those reported by other transplantation groups and confirm the important role of the HLA antigens in the outcome of renal transplantation.

Actuarial Analysis

Quantification of the soluble receptor of human T lymphocytes for sheep erythrocytes in the serum of patients with aplastic anaemia.

The soluble E-receptor (Rs) of human T lymphocytes for sheep erythrocytes has been quantified by electroimmunodiffusion ("rocket" electrophoresis) in serum samples from 23 patients with aplastic anaemia and 43 controls. A statistically significant increase of Rs levels was found in the group of patients as compared with controls. Sixteen patients showed Rs values greater than the mean +2SD of the control group. No correlation between Rs values and the number of circulating total lymphocytes or T lymphocytes was observed. Since Rs serum levels have previously been shown to be increased in diseases associated with depressed cell mediated immunity, the finding of high levels of Rs in most cases of aplastic anaemia may contribute to the understanding of the pathogenesis of this disease.

Adolescent