M T Rezkallah-Iwasso

Energy Biosciences Institute, Berkeley, California, United States

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Publications (17)24.8 Total impact

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    ABSTRACT: High (H) and low (L) responder mice were selected for their ability to produce antibodies against sheep and human erythrocytes (Selection IV-A). In this selection, the difference in antibody responsiveness between H and L lines (HIV-A and LIV-A mice, respectively) was shown to depend mainly on macrophage function. The more rapid catabolism of antigens by macrophages in L mice has been suggested as the main cause of the low antibody production. Due to this high macrophage activity, L animals have been described as more resistant than H animals to intracellular pathogens. These animals were utilized as an experimental model of paracoccidioidomycosis. HIV-A and LIV-A mice were infected with Paracoccidioides brasiliensis by the intravenous route. As expected, H mice were more susceptible to P. brasiliensis with a shorter survival time and higher levels of specific antibodies when compared to L mice. Contrasting with the survival time, the lungs, spleen and liver from H mice showed typical nodular granulomas containing epithelioid and giant cells and few fungi. On the other hand, in LIV-A mice, the lesions of these organs were characterized by looser granulomas with irregular borders and the presence of a large number of fungi. However, the adrenal gland showed different lesion patterns. In H mice these lesions were extensive and characterized by loose granulomas with numerous fungi, while in LIV-A mice the lesions were small and limited to the cortex. Moreover the HIV-A mice presented higher levels of serum corticosterone when compared to LIV-A ones. The higher susceptibility of H mice could be attributed to the extensive lesions of the adrenal glands. These results suggest the use of the H line from the IV-A Selection as an experimental model for further studies of adrenal involvement in paracoccidioidomycosis.
    No preview · Article · Sep 2000 · Medical Mycology
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    ABSTRACT: The aim of the present investigation was to study the distribution of T-cell subsets in peripheral blood defined by monoclonal antibodies and by the lymphocyte proliferative response to phytohemagglutinin (PHA) in 30 children with febrile seizures and in 14 age-matched control subjects. Frequent respiratory, urinary and dermatologic infections were observed in 22 patients. The immunologic parameters showed that 64% of the patients presented an increased number of CD8+ cells and a low helper/suppressor ratio was observed in 60% of the patients. In addition, the proliferative response of lymphocytes to PHA was impaired in the patients. It was observed the presence of inhibitory activity on lymphocyte function in the plasma of 33% of children with febrile seizures. These results suggest that patients with febrile seizures have an impairment of cellular immunity that may be connected with this epileptic syndrome and explain the infections observed.
    Full-text · Article · Jul 1997 · Arquivos de Neuro-Psiquiatria
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    ABSTRACT: A group of 10 patients, nine of them seriously infected with Paracoccidioides brasiliensis (G1), received glucan (beta-1,3 polyglucose) as an immunostimulant intravenously once a week for one month, followed by monthly doses (10 mg) over an 11-month period, together with a specific anti-fungal agent as an immunostimulant. A second group of eight moderately infected patients (G2) was treated with only the anti-fungal agent. Among the patients in G1, there was only one case of relapse compared with five in G2. Values for the erythrocyte sedimentation rate (ESR) showed a significant difference (P < 0.001) post-treatment in G1 patients, when compared with the pretreatment levels. There was also a significant reduction (P < 0.001) in the level of serum antibodies to P. brasiliensis in the G1 patients in post-treatment examinations. The phytohemagglutinin (PHA) skin test showed a positive reaction among the patients in G1 (P < 0.01) post-treatment and there was a tendency towards an increase in the number of CD4+ T lymphocytes in both groups after treatment. The serum level of tumor necrosis factor (TNF) proved to be significantly higher (P < 0.02) in the G1 patients during treatment. In the G1 patients, the correlation between ESR and TNF tended to be negative whereas that between ESR and serum antibodies was positive. The present results indicate that the patients who received glucan, in spite of being more seriously ill, had a stronger and more favorable response to therapy.
    No preview · Article · Nov 1996 · The American journal of tropical medicine and hygiene
  • J C Peraçoli · M R Fortes · M V Rudge · M T Rezkallah-Iwasso · M T Peraçoli
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    ABSTRACT: The number and activity of natural killer (NK) cells were studied in 20 patients with pregnancy-induced hypertension (PIH), 15 uncomplicated pregnant women and 16 healthy non-pregnant women. All the pregnant women were primigravidae and were evaluated during the third trimester of gestation. Peripheral blood NK cells were detected with monoclonal antibodies by indirect immunofluorescence and cytotoxic activity was measured using a single-cell assay against K562 target cells. Hypertensive pregnant women had an increased number of circulating NK cells associated with a significant decrease of NK activity. The cytotoxic activity was significantly lower in normal pregnant and PIH women when compared with non-pregnant controls. The onset of immature NK cells in peripheral blood and the impairment of their cytotoxic activity in PIH patients may be associated with hormones and immunosuppressive substances produced by tissues occurring at the maternal-fetal interface.
    No preview · Article · Jul 1995 · Brazilian Journal of Medical and Biological Research
  • M.T.S. Peraçoli · M T Rezkallah-Iwasso · N. G. S. Mota · M R Montenegro
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    ABSTRACT: The effect of dialysable leukocyte extracts (DLE) obtained from hamsters immunized with Paracoccidioides brasiliensis (immune DLE) and from non-immunized hamsters (non-immune DLE) was studied in hamsters inoculated with P. brasiliensis by the intratesticular route. Treatment with immune or non-immune DLE was started during the third week of infection and was repeated at 7, 11, 15 and 19 weeks. A group of untreated infected animals was used as control. Animals were submitted to the delayed hypersensitivity skin test to P. brasiliensis antigen (PbAg) in vivo and assayed in vitro by the macrophage migration inhibition test in the presence of Phytohemagglutinin (PHA) and PbAg and by immunodiffusion for specific antibody. The animals were sacrificed at 4, 8, 12, 16 and 20 weeks. The morphology and extension of the lesions were studied at the inoculation site, and in lymph nodes, lungs, liver, spleen and kidneys. In contrast to the controls, animals treated with both DLEs maintained a positive cell-mediated immune response throughout the experiment and developed less extensive infection with a significantly lower number of fungi in the lesions. The results suggest that immune and non-immune DLE preparations modified the evolution of experimental paracoccidioidomycosis with equal efficiency. This similarity may be explained by the immunoregulatory activities of both extracts.
    No preview · Article · Apr 1993 · Mycopathologia
  • J Defaveri · M T Rezkallah-Iwasso · M F Franco
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    ABSTRACT: Paracoccidioidomycosis was induced in immunized (IM) and non-immunized (NI) mice. The histopathology, the number of fungi in the lungs, the cellular (footpad test--FPT and macrophage inhibition factor assay--MIF) and humoral (immunodiffusion test) immune response were investigated serially post-infection. In the IM mice, at days 1 and 3, there was intense and predominant macrophagic-lymphocytic alveolitis with loose granulomatous reaction; at day 30, inflammation was mild. In the NI group, up to day 3, the lesions were focal; later there was formation of extensive epithelioid granuloma. The number of fungi in IM mice were always smaller than those of NI group. Immunization alone induced positive FPT and MIF indices with low titer of antibody. After infection, there was a significant decrease of the FPT indices in the IM group, which we interpreted as desensitization due to trapping of sensitized lymphocytes in the lungs. In conclusion, (1) The lesional pattern of pulmonary paracoccidioidomycosis in IM mice was similar to that of a hypersensitivity pneumonitis. This reaction was probably effective in reducing the extension of the infection and decrease the number of fungi. (2) In this model, pulmonary resistance against P. brasiliensis seems to be related to local and systemic delayed-type hypersensitivity reaction.
    No preview · Article · Aug 1992 · Mycopathologia
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    ABSTRACT: The number and activity of natural killer (NK) cells were studied in 34 untreated patients with paracoccidioidomycosis, 20 with the chronic form of the disease and 14 with the acute form. NK cells were detected with monoclonal antibody Leu-11c and the cytotoxic activity was measured using a single cell assay against K562 target cells. Both groups of patients had an increased number of circulating NK cells, their cytotoxic activity being significantly lower than in the healthy controls. These findings may be of importance in the immunological disturbances associated with paracoccidioidomycosis since NK cells exert important immune effector functions and may play a role in resistance against Paracoccidiodes brasiliensis.
    No preview · Article · Feb 1991 · Journal of medical and veterinary mycology: bi-monthly publication of the International Society for Human and Animal Mycology
  • J Defaveri · K.I.R. Coelho · M.T. Rezkallah-Iwasso · Franco MF
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    ABSTRACT: Hypersensitivity pneumonitis was induced in mice immunized with Paracoccidioides brasiliensis and challenged, one week later, with soluble (SPbAg) or particulate (PPbAg) antigen (formalin-killed yeast cells), administered by the intratracheal route. Between 24 and 48 h post-challenge, animals developed an interstitial and intra-alveolar pneumonitis. Macrophages and lymphocytes arranged focally into loose or mature granulomata were observed by light and electron microscopy. The distribution and fate of antigens was studied by immunofluorescence. Three hours after challenge with SPbAg the lungs showed linear fluorescent deposits, whereas after challenge with PPbAg the pattern was globular, corresponding to the particulate antigen. After 24 and 48 h, the pattern was diffuse and finely granular in both groups, with a decreasing number of animals showing detectable fluorescence. Immunization induced a positive footpad swelling test (FPT) in all animals. After pulmonary challenge, there was a significant decrease in FPT indices, interpreted as desensitization due to trapping of specifically sensitized lymphocytes in the lungs. In conclusion, immunization induced a marked cellular immune response, the inflammatory pattern and the tempo of the induced pneumonitis being compatible with delayed hypersensitivity in the lungs. Immunized mice also cleared the injected antigens rapidly. These data suggest that hypersensitivity pneumonitis may be an expression of pulmonary resistance to infection with P. brasiliensis.
    No preview · Article · Feb 1989 · Journal of medical and veterinary mycology: bi-monthly publication of the International Society for Human and Animal Mycology
  • A Kamegasawa · R M Viero · M T Rezkallah-Iwasso · M F Franco
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    ABSTRACT: The present study reproduced the experimental model of ocular paracoccidioidomycosis in guinea pigs, by the intracardiac inoculation of yeast-forms of P. brasiliensis. Ocular involvement was observed in 80% of the infected animals. The uvea, ciliary body, choroid, iris, lids and the conjunctiva were the structures most commonly affected. To protect the animals against the infection, an immunization protocol was standardized utilizing a P. brasiliensis soluble antigen in Freund's complete adjuvant, administered weekly, during 3 weeks, by the subcutaneous route. Two weeks later, previously immunized guinea pigs were challenged by the intracardiac route with yeast-forms of P. brasiliensis (vaccinated group). When compared with a control group (infection in the absence of prior immunization), the vaccinated animals developed higher levels of anti-P. brasiliensis cellular and humoral immune response and a three times lower frequency of ocular involvement (85.7% vs 28.5%). In addition, the ocular lesions were significantly more localized and contained less fungal cells. The data demonstrated that the subcutaneous immunization was effective in decreasing the frequency and extent of ocular lesions, as well as in blocking fungal multiplication.
    No preview · Article · Aug 1988 · Mycopathologia
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    ABSTRACT: Seventy untreated paracoccidioidomycosis patients, 15 with the acute or subacute form of the disease and 55 with the chronic form, were compared with two normal control groups of the same age range. Peripheral blood mononuclear cell subsets were defined by monoclonal antibodies directed at total T cells, helper/inducer and suppressor/cytotoxic T cell subpopulations; B cells, cortical thymocytes and monocyte/null cells. Both groups of patients showed an increased number of monocyte/null cells, a low helper/suppressor ratio and a reduced percentage of total T cells and their helper/inducer subsets. In addition patients with the acute form of the disease exhibited high levels of suppressor/cytotoxic T cells and B cells. These findings are of importance in our attempts to understand the pathogenesis of this mycosis and also to evaluate its prognosis in individual patients.
    No preview · Article · May 1988 · Journal of medical and veterinary mycology: bi-monthly publication of the International Society for Human and Animal Mycology
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    ABSTRACT: Cellular immune response to specific and non-specific stimulants was investigated, both in vivo and in vitro, in 29 healthy controls and in 53 previously untreated patients with the chronic isolated organic form (CIOF), the chronic mixed form (CMF) and the acute progressive form (APF) of paracoccidioidomycosis. The study included skin tests to Paracoccidioides brasiliensis antigen (PbAg) and phytohaemagglutinin (PHA), DNCB sensitization, determination of T lymphocytes and complement rosette-forming cells, lymphocyte transformation and leucocyte migration inhibition tests using PbAg and PHA. Patients displayed staggered cutaneous response to PHA and to PbAg, with marked decrease in intensity in the APF group. DNCB sensitization test and proliferative response of lymphocytes to PHA and PbAg were severely depressed in most of the patients. Leucocyte migration inhibition indices to PbAg were highly positive, while response to PHA was slightly decreased regardless of the clinical form. The number of T lymphocytes was reduced in most of patients and in them the number of complement-rosette forming cells was normal. The distribution of patients according to a suppression index, based in the results of the tests employed, revealed a tendency towards an increased degree of cellular immunosuppression from the least severe (CIOF) to the most severe (APF) clinical form of the disease. On the whole, the present study demonstrated a gamut of immunological reactivity in paracoccidioidomycosis.
    No preview · Article · Feb 1985 · Transactions of the Royal Society of Tropical Medicine and Hygiene
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    ABSTRACT: The effect of Ketoconazole (KTZ) on the hamster experimental intratesticular paracoccidioidomycosis was studied employing different treatment schedules. KTZ long course treatment beginning at an early stage of the infection was effective in preventing fungal proliferation, dissemination to lymph nodes, spleen and kidneys, and in maintaining low levels of humoral and cellular specific immune responses. KTZ short course treatment starting at an advanced stage of disease resulted in a more severe histopathological picture without significant changes in the immunological profile. The drug prolonged the life span of hamsters infected with Paracoccidioides brasiliensis, but did not prevent mortality. Toxic necrosis of the bone marrow occurred in normal animals receiving 120 mg/kg/day of KTZ but with lower doses no morphologic alterations were observed in heart, lungs, kidneys, adrenals, spleen, liver, intestine or bone marrow.
    No preview · Article · Jan 1985 · Mycopathologia
  • M T Rezkallah-Iwasso · N. G. S. Mota · M. C. G. Gomes · M R Montenegro
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    ABSTRACT: The effect of levamisole (LMS) was studied in hamsters inoculated with live yeast phase culture of Paracoccidioides brasiliensis by intratesticular route. One group started LMS therapy at an early stage of infection (LMS3 group), when the animals were immunocompetent, and another group was treated in a later stage, when the immune response was already depressed (LMS12 group). As control, one group was not treated. The alterations induced by levamisole were studied by immunologic and histopathologic parameters. Compared to controls, the LMS3 group presented normal levels of cellular immune response and inflammatory reaction characterized by compact epithelioid granuloma during a longer period of time. In addition, this group showed a lower incidence of amyloidosis and lower fungi proliferation in the lesions. In the LMS12 group a transient enhancement was noteworthy of cellular immune response with maintenance of the compact pattern of the epithelioid granuloma as in the LMS3 group; however, the number of fungi and incidence of amyloidosis were similar to controls. The differences between both treated groups may be accounted for by some factors such as host immune competence, timing and total dose of LMS administered. Levamisole may be of value as additional therapy in paracoccidioidomycosis.
    No preview · Article · Mar 1984 · Mycopathologia
  • Y Kiy · M T Rezkallah-Iwasso · M. T. S. PERAÇOLI · N. G. S. MOTA
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    ABSTRACT: Cell-mediated and humoral immunity were studied in seventeen patients with toxic multinodular goitre, ten with active Graves' disease and fourteen healthy controls. The study included determination of sheep erythrocyte and complement rosette-forming cells in the peripheral blood, immunoglobulin levels, titres of microsomal antibodies and migration inhibition test using thyroid extract and phytohaemagglutinin. When compared with controls the patients showed a positive response to thyroid antigen in the leucocyte migration inhibition test. Microsomal antibodies were detected in seven out of ten active Graves' disease patients against two out of seventeen of those with toxic multinodular goitre. Significantly increased IgG and IgA and deceased IgM levels were found only in the toxic multinodular group. These data provide further evidence for immunological disturbances in toxic multinodular goitre.
    No preview · Article · Feb 1982 · Clinical Endocrinology
  • J Defaveri · M T Rezkallah-Iwasso · M F de Franco
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    ABSTRACT: The present paper describes a murine model for pulmonary paracoccidioidomycosis injecting 6×105 yeast forms ofParacoccidioides brasiliensis (Pb) by the direct intratracheal route. The sequential histopathology of lung and dissemination lesions together with humoral (immunodiffusion test) and cellular immune response (footpad test and macrophage inhibition factor assay — MIF assay) were investigated since the 1st to the 360th day after infection. All infected animal showed pulmonary Pbmycosis up to Day 30; onwards the lesions subsided being found only in one mouse at Day 360. Dissemination lesions were observed in paratracheal and cervical lymph nodes in 9 out of 68 infected animals. Histologically early lesions were rich in polymorphonuclear cells and evolved to a macrophage desquamative pneumonitis at Day 15 and to typical epithelioid granulomata from Day 30 up to Day 360. Specific precipitating antibodies were first detected 15 days after infection, peaked from Day 30 to 60 and were not observed at Day 360. Significant cell-mediated immunity to Pb was noted at Day 15 with the peak reaction at Day 60 and 90. The intratracheal route represents a highly effective way of infecting mouse with Pb. This experimental pulmonary Pbmycosis is a granulomatous inflammation which courses with specific humoral and cellular immune response. It may be a good tool for further investigation in the pathogenesis and natural history of the disease.
    No preview · Article · Feb 1982 · Mycopathologia
  • N. G. S. Mota · Y Kiy · M T Rezkallah-Iwasso · M. T. S. Peraçoli
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    ABSTRACT: Humoral and cell-mediated immunity was investigated in fourteen patients with non-toxic multinodular goitre and ten healthy controls by in vitro methods. These included determination of sheep erythrocyte and complement rosette-forming cells in the peripheral blood, immunoglobulin levels, titres of thyroglobulin and microsomal antibodies and migration inhibition test using thyroid extract and phytohemagglutinin. When compared with controls the patients showed high IgA levels and positive response to thyroid antigen in the leucocyte migration inhibition test. There was no correlation between the leucocyte migration results and the presence of auto-antibodies. These findings indicate a possible role of cell-mediated immunity in non-toxic multinodular goitre.
    No preview · Article · Sep 1980 · Clinical Endocrinology
  • C.C. Musatti · M.T.S. Peraçoli · A.M.V.C. Soares · M.T. Rezkallah-Iwasso

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Publication Stats

292 Citations
24.80 Total Impact Points


  • 1989-2000
    • Energy Biosciences Institute
      Berkeley, California, United States
  • 1980-1997
    • São Paulo State University
      • • Department of Microbiology and Immunology
      • • Department of Obstetrics and Gynecology
      San Paulo, São Paulo, Brazil