CLEUSA FUMICA HIRATA TAKAKURA

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  • article 1 Citação(ões) na Scopus
    Esophageal mucosa in HIV infection: A ""deeper"" look at this little spoken organ
    (2017) WERNECK-SILVA, Ana Luiza; PAGLIARI, Carla; PATZINA, Roseli A.; TAKAKURA, Cleusa Fumica Hirata; DUARTE, Maria Irma
    Background and Aim: Although the esophagus is a common site of opportunistic infection in AIDS patients, little is known about the impact of HIV as well as opportunistic infection in the esophageal mucosa. Our aim is to analyze the esophageal immune profile in HIV+ patients with different immunological status with and without the opportunistic Candida infection. Methods: Immunohistochemistry to CD4+ and CD8+ T-cells, gamma-interferon, transforming growth factor-beta, interleukin (IL)-4, IL-6, IL-13, and IL-17 was performed in esophageal samples of 40 chronically HIV+ patients under highly active antiretroviral therapy (16 with Candida esophagitis, 12 virologically non-supressed with blood CD4 count < 500, and 12 virologically suppressed with blood CD4 count > 500; the latter two groups without esophageal candidiasis). The controls were 12 HIV-negative healthy individuals. Results: Esophageal CD4+ T-cell expression in HIV+ patients did not differ from the control group (P = 0.50). Mucosal CD8+ T-cell expression was significantly increased in HIV+ patients (P = 0.0018). Candida esophagitis and virologically non-supressed HIV+ patients with CD4 < 500 showed an increased expression of IL-17 and IL-6 with fewer expressions of gamma-interferon, more attenuated in the latter group. Transforming growth factor-beta was increased only in virologically suppressed HIV+ patients with CD4 > 500. IL-4 and IL-13 were similar to the control group. Conclusion: In contrast to CD8+ T-cell expression, esophageal CD4+ T-cell expression does not reflect the HIV+ patient's immunological status. T-helper 17 (Th17) response seems to play a role in the esophageal mucosa of virologically non-supressed HIV+ patients with blood CD4 < 500. Candida esophagitis showed a Th1/ Th17 response but seems to be dominantly regulated by the Th17 pathway.
  • article 7 Citação(ões) na Scopus
    Liver disease accompanied by enteropathy in common variable immunodeficiency: Common pathophysiological mechanisms
    (2022) LIMA, Fabiana Mascarenhas Souza; TOLEDO-BARROS, Myrthes; ALVES, Venancio Avancini Ferreira; DUARTE, Maria Irma Seixas; TAKAKURA, Cleusa; BERNARDES-SILVA, Carlos Felipe; MARINHO, Ana Karolina Barreto Berselli; GRECCO, Octavio; KALIL, Jorge; KOKRON, Cristina Maria
    Common variable immunodeficiency (CVID) is one of the inborn errors of immunity that have the greatest clinical impact. Rates of morbidity and mortality are higher in patients with CVID who develop liver disease than in those who do not. The main liver disorder in CVID is nodular regenerative hyperplasia (NRH), the cause of which remains unclear and for which there is as yet no treatment. The etiology of liver disease in CVID is determined by analyzing the liver injury and the associated conditions. The objective of this study was to compare CVID patients with and without liver-spleen axis abnormalities in terms of clinical characteristics, as well as to analyze liver and duodenal biopsies from those with portal hypertension (PH), to elucidate the pathophysiology of liver injury. Patients were divided into three groups: Those with liver disease/PH, those with isolated splenomegaly, and those without liver-spleen axis abnormalities. Clinical and biochemical data were collected. Among 141 CVID patients, 46 (32.6%) had liver disease/PH; 27 (19.1%) had isolated splenomegaly; and 68 (48.2%) had no liver-spleen axis abnormalities. Among the liver disease/PH group, patients, even those with mild or no biochemical changes, had clinical manifestations of PH, mainly splenomegaly, thrombocytopenia, and esophageal varices. Duodenal celiac pattern was found to correlate with PH (p < 0.001). We identified NRH in the livers of all patients with PH (n = 11). Lymphocytic infiltration into the duodenal mucosa also correlated with PH. Electron microscopy of liver biopsy specimens showed varying degrees of lymphocytic infiltration and hepatocyte degeneration, which is a probable mechanism of lymphocyte-mediated cytotoxicity against hepatocytes and enterocytes. In comparison with the CVID patients without PH, those with PH were more likely to have lymphadenopathy (p < 0.001), elevated beta(2)-microglobulin (p < 0.001), low B-lymphocyte counts (p < 0.05), and low natural killer-lymphocyte counts (p < 0.05). In CVID patients, liver disease/PH is common and regular imaging follow-up is necessary. These patients have a distinct immunological phenotype that may predispose to liver and duodenal injury from lymphocyte-mediated cytotoxicity. Further studies could elucidate the cause of this immune-mediated mechanism and its treatment options.
  • article 10 Citação(ões) na Scopus
    Detection of Toxoplasma gondii in two southern Wooly spider monkeys (Brachyteles arachnoides - Geoffroy, 1806) from the Rio de Janeiro primate center, Brazil
    (2014) SANTOS, S. V.; STREFEZZI, R. F.; PISSINATTI, A.; KANAMURA, C. T.; TAKAKURA, C. F. H.; DUARTE, M. I. S.; CATAO-DIAS, J. L.
    BackgroundToxoplasmosis led to the death of two Brachyteles arachnoides, an endangered atelid. MethodsThe diagnosis was established by necropsy, histopathological, immunohistochemical and ultrastructural changes. ResultsThe analysis confirms the presence of Toxoplasma gondii. ConclusionsThis report contributes to the development of protocols for health surveillance on maintenance and conservation of southern muriquis.
  • article 6 Citação(ões) na Scopus
    Ultrastructure of Vascular Permeability in Urticaria
    (2013) CRIADO, Paulo R.; CRIADO, Roberta F. J.; TAKAKURA, Cleusa F. H.; PAGLIARI, Carla; CARVALHO, Jozelio F. de; SOTTO, Mirian N.; VASCONCELLOS, Cidia
    Background: Few studies have addressed the ultrastructure of vascular permeability in urticaria. Objectives: To describe the types of endothelial cell organelles involved in vascular permeability in drug induced acute urticaria (DIAU). Methods: Seven patients with DIAU were enrolled in the study. Biopsies of urticarial lesions and apparently normal skin were performed. The 14 collected fragments were processed with immunogold electron microscopy using single stains for tryptase and factor XIIIa (FXIIIa) and double immunogold labeling for both tryptase and FXIIIa. Results: Some sections demonstrated mast cells in the degranulation process, in both anaphylactic and piecemeal degranulation. After double immunogold staining, 10 nm (FXIIIa) and 15 nm (tryptase) gold particles were both present, covering the granules in the mast cells, indicating that both tryptase and FXIIIa were localized within the granules of these cells. Interestingly, we found strong evidence of the presence of caveolae and vesico-vacuolar organelles (VVOs) in the endothelial cells of the biopsies. In addition to these findings, we were able to demonstrate the presence of tryptase and FXIIIa in the endothelial cells, in urticarial lesions and in apparently normal skin. Conclusions: VVOs are present in the endothelial cells of post capillary venules in DIAU. This is the first report on the expression of FXIIIa and tryptase in the cytoplasm of endothelial cells in urticaria.
  • article 0 Citação(ões) na Scopus
    Immunoelectron microscopy study of superficial skin nerves in drug-induced acute urticaria
    (2012) CRIADO, Paulo Ricardo; CRIADO, Roberta Fachini Jardim; TAKAKURA, Cleusa F. H.; PAGLIARI, Carla; SOTTO, Mirian Nacagami; VASCONCELLOS, Cidia
    BACKGROUND: Few studies have evaluated the ultrastructure of the superficial skin nerves in urticaria. OBJECTIVE: The objective of this study was to describe findings in superficial skin nerves in cases of drug-induced acute urticaria. METHODS: Seven patients with drug-induced acute urticaria were included in the study. Skin biopsies were obtained from the urticarial lesion and from the apparently normal skin. The 14 fragments collected were processed for immunogold electron microscopy using single stains for antitryptase and anti-FXIIIa antibodies, as well as double immunogold labeling for both. RESULTS: Some sections showed mast cells in the process of degranulation. Following double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were found together throughout the granules in mast cells, indicating that tryptase and FXIIIa are located inside each one of the granules of these cells. Interestingly, we found strong evidence of the presence of tryptase and factor XIIIa in the superficial skin nerves of these patients, both in cases of urticarial lesions (wheals) and in the apparently normal skin. CONCLUSIONS: Tryptase and FXIIIa are present in the superficial nerves of the skin in drug-induced acute urticaria. This is the first report of tryptase and FXIIIa expression in the superficial skin nerves of patients with urticaria. Tryptase may be participating in neural activation in these patients, while FXIIIa may be present in the nerves to guarantee the functional integrity of structures.
  • article 9 Citação(ões) na Scopus
    Renal Lesions in Cetaceans from Brazil
    (2015) GONZALES-VIERA, O.; RUOPPOLO, V.; MARIGO, J.; CARVALHO, V. L.; GROCH, K. R.; BERTOZZI, C. P.; TAKAKURA, C.; NAMIYAMA, G.; VANSTREELS, R. E. T.; CATAO-DIAS, J. L.
    This study reports the occurrence of renal lesions in cetaceans from the coast of Brazil subjected to necropsy examination between 1996 and 2011. The animals (n = 192) were by-caught in fishing nets, were found dead on beaches or died despite attempted rehabilitation. Kidney samples were evaluated grossly and microscopically and, depending on the histopathological findings, immunohistochemical and ultrastructural analyses were conducted. Due to autolysis, a diagnosis was reached in only 128 animals, of which 82 (64.1%) had kidney lesions. Cystic renal disease was the most common lesion observed in 34 cases (26.6%) and these were classified as simple cysts in eight cases (6.3%), polycystic kidney disease in one rough-toothed dolphin (Steno bredanensis), secondary glomerulocystic disease in 16 cases (12.5%) and primary glomerulocystic disease in nine cases (7%). Other lesions included membranous glomerulonephritis (28 cases; 21.9%), membranoproliferative glomerulonephritis (20 cases; 15.6%), lymphoplasmacytic interstitial nephritis (21 cases; 16.4%), lipidosis (19 cases; 14.8%), glomerulosclerosis (8 cases; 6.3%) and pyogranulomatous nephritis (five cases; 3.9%); two of the later were associated with the migration of nematode larvae. Additionally, tubular adenoma was identified in a Franciscana (Pontoporia blainvillei). The pathological implications of these lesions are discussed according the cause of death, age or sex of the animals. Furthermore, the lesions were compared with those of other marine and terrestrial mammals, including man.
  • article 7 Citação(ões) na Scopus
    Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes
    (2019) MENDONCA, Daiane Barros Dias; SILVA, Renata Ellen Costa; PALACE-BERL, Fanny; TAKAKURA, Cleusa F. H.; SOARES, Sandra Regina C.; BRAZ, Lucia Maria Almeida; TAVARES, Leoberto Costa; LINDOSO, Jose Angelo Lauletta
    Background: Three drugs - pentavalent antimonials, amphotericin B and pentamidine - are currently used for leishmaniasis treatment. They are administered for long periods, only parenterally, and have high cardiac, renal and hepatic toxicities. Therefore, the investigation of new compounds is required. Nitro-heterocyclic derivatives have been used as possible drug candidates to treat diseases caused by trypanosomatids. Methods: Leishmania (L.) amazonensis promastigotes (MHO/BR/73/M2269), maintained in the Laboratorio de Soroepidemiologia - Instituto de Medicina Tropical-USP, were exposed to five nitroheterocyclic derivatives, with differences at phenyl-ring position 4: BSF-C4H9, BSF-H, BSF-NO2, BSF-CH3 and BSF-Cl, for 48 hours. After analyzing viability (MTT assay), we evaluated cellular-morphology activity of compounds by transmission electron microscopy (TEM) and measurement of apoptosis (phosphatidylserine expression) by flow cytometry. Results: EC50 of amphotericin B and BSF-CH3 were 0.50 mu M and 0.39 mu M respective. Other nitro-heterocyclic compounds presented EC50 higher than amphotericin B. All compounds showed greater AV - and PI-positive expression than amphotericin B at 100 mu M, except BSF-NO2. TEM showed complete nuclear disfigurement with 100 mu M of BSF-NO2, 25 and 6.25 mu M of BSF-H, and 6.25 mu M BSF-Cl; presence of vesicles within the flagellar pocket with 25 mu M BSF-H; alteration of the kinetoplast with 25 mu M BSF-C4H9, 25 mu M of BSF-H, 6.25 mu M BSF-CH3 and 6.25 mu M of BSF-Cl. Conclusions: Nitro-heterocyclic compounds have shown activity against promastigotes of L. amazonensis, at lower concentrations. However, improvement of compound scaffolds are needed to assist the elucidation of the mechanism of action and to achieve greater activity.
  • article 8 Citação(ões) na Scopus
    Dermal dendrocytes FXIIIA+ phagocytizing extruded mast cell granules in drug-induced acute urticaria
    (2013) CRIADO, P. R.; CRIADO, R. F. Jardim; SOTTO, M. N.; PAGLIARI, C.; TAKAKURA, C. H.; VASCONCELLOS, C.
    Background Few authors have been attempting between mast cells and dermal dendrocytes interactions on urticaria. Objective To describe the extruded mast cell granules and dermal dendrocytes in drug-induced acute urticaria. Methods Seven patients with drug-induced acute urticaria were enrolled in the study. We token skin biopsies of urticaria lesion and perilesional skin. The 14 fragments collected were processed to immunogold electron microscopy using single stains to tryptase and FXIIIa, besides double immunogold labeling with both. Results Some sections demonstrated mast cells in degranulation process, both in anaphylactic and piecemeal degranulation types. After double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were present together over the granules in mast cells indicating that tryptase and FXIIIa are each localized within the granules of these cells. Interestingly, we found a strong evidence of than the exocytosed mast cell granules contents both FXIIIa and tryptase immunolabeled are phagocytized by dermal dendrocytes. Conclusions The current observations provide morphological evidence that the exocytosis-phagocytosis mechanisms of mast cell granules represents one pathophysiological example of mast cells-dermal dendrocytes interactions in urticaria.
  • article 20 Citação(ões) na Scopus
    Toxoplasmosis in a Guiana dolphin (Sotalia guianensis) from Parana, Brazil
    (2013) GONZALES-VIERA, O.; MARIGO, J.; RUOPPOLO, V.; ROSAS, F. C. W.; KANAMURA, C. T.; TAKAKURA, C.; FERNANDEZ, A.; CATAO-DIAS, J. L.
    This study describes toxoplasmosis in a by caught Guiana dolphin (Sotalia guinensis) from Paranagua Bay, Parana, Brazil. Interstitial pneumonia, multisystemic arteritis, multifocal adrenalitis and hepatitis were the primary lesions observed. These tissues had moderate to severe necrosis and mononuclear cells infiltration usually surrounded by tachyzoites and tissue cysts. Moderate lymphoid depletion was evident in the spleen. Toxoplasma gondii was positive by immunohistochemical and ultrastructural evaluation. Furthermore, the animal was negative for Morbillivirus by immunohistochemistry and had low levels of persistent organochlorines. There is evidence of environmental changes in the Paranagua Bay that could justify the occurrence of toxoplasmosis in Guiana dolphin. The sewage run-off from main urban areas and the presence of domestic and wild felids in areas surrounding the bay could be a source of T. gondii oocysts from land to sea. Based on its habitat, the authors recommend this dolphin species as sentinels for the health of bays and estuaries where they occur. Crown
  • article 28 Citação(ões) na Scopus
    Yellow fever and orthotopic liver transplantation: new insights from the autopsy room for an old but re-emerging disease
    (2019) DUARTE-NETO, Amaro N.; CUNHA, Marielton dos P.; MARCILIO, Izabel; SONG, Alice T. W.; MARTINO, Rodrigo B. de; HO, Yeh-Li; POUR, Shahab Z.; DOLHNIKOFF, Marisa; SALDIVA, Paulo H. N.; DUARTE, Maria I. S.; TAKAKURA, Cleusa F.; LIMA, Fabiana R.; TANIGAWA, Ryan Y.; IGLEZIAS, Silvia D'A; KANAMURA, Cristina T.; SANTOS, Angela B. G. dos; PERONDI, Beatriz; ZANOTTO, Paolo M. de A.; D'ALBUQUERQUE, Luiz A. C.; ALVES, Venancio A. F.
    Aims The clinical spectrum of yellow fever (YF) ranges from asymptomatic to fulminant hepatitis. During the sylvatic YF epidemic in the metropolitan area of Sao Paulo, Brazil in 2018, seven orthotopic liver transplantations (OLTs) were performed in our institution to treat fulminant YF hepatitis. Three patients recovered, while four patients died following OLT. The autopsy findings of all these cases are presented herein as the first description of YF in transplanted patients. Methods and results All patients were men, aged 16-40 years, without vaccination to YF virus (YFV). All organs were examined, with tissue sampling for histopathological analysis. Detection of YF virus antigens (YFV Ag) was performed with two primary antibodies (mouse polyclonal anti-YFV antibody directed to wild strain and a goat anti-YF virus antibody), and RT-PCR assays were utilised to detect YFV-RNA. All the cases depicted typical findings of YF hepatitis in the engrafted liver. The main extrahepatic findings were cerebral oedema, pulmonary haemorrhage, pneumonia, acute tubular necrosis and ischaemic/reperfusion pancreatitis. Of the four cases, the YVF Ag was detected in the heart in one case, liver and testis in three cases, and the kidney and spleen in all four cases. All four cases had YF virus RNA detected by RT-PCR in the liver and in other organs. Conclusions Infection of the engrafted liver and other organs by YFV, possibly combined with major ischaemic systemic lesions, may have led to the death of four of the seven patients undergoing OLT.