MIRIAN NACAGAMI SOTTO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Unilateral Livedoid Vasculopathy Associated With Involutional Phase of Cutaneous Infantile Hemangioma: The Connection to Coagulation Disorders(2013) CRIADO, Paulo Ricardo; ALAVI, Afsaneh; HALPERN, Ilana; SOTTO, Mirian Nacagami; KIRSNER, Robert S.Livedoid vasculopathy is a bilateral painful and recurrent cutaneous ulcerative disorder of the legs that leads to atrophie blanche, atrophic white-porcelain scars, and is associated with disorders of fibrinolysis and/or coagulation. We present a young boy with an association between livedoid vasculopathy in the area of a previous involuted cutaneous hemangioma. We found 4 uncommon abnormalities associated with thrombo-occlusive events: heterozygous 20210 AG genotype of prothrombin, reduced activity of anticoagulation proteins C and S, and elevated lipoprotein (a).
- Analysis of serum levels and cutaneous expression of lipoprotein (a) in 38 patients with livedoid vasculopathy(2017) ESPINEL, Danielle P. G. S.; GIACOMO, Thais B. Di; PINCELLI, Thais P.; PEREIRA, Naiura V.; SOTTO, Miriam N.; KIRSNER, Robert S.; CRIADO, Paulo R.BackgroundCoagulation disorders contribute to the development of livedoid vasculopathy (LV). Elevated plasma levels of lipoprotein(a) [Lp(a)] are an independent risk factor for the development of cardiovascular disease and associated with hypercoagulable states. Increased serum Lp(a) levels have been reported in patients with LV and may have an important role in the pathogenesis of LV. ObjectivesTo investigate Lp(a) expression in skin lesions and circulating serum Lp(a) levels in patients with LV. MethodsSkin biopsy samples from 38 patients (27 women and 11 men) with active lesions diagnosed as LV and 9 samples of normal skin (5 women and 4 men) from control patients without LV were evaluated for skin expression of Lp(a) by immunohistochemistry. Plasma levels of Lp(a) were analyzed by immunoturbidimetry. ResultsWe found that lesional skin in patients with LV expressed 10-fold higher Lp(a) immunostaining than controls. High plasma levels of Lp(a) were observed in LV patients. We did not find a correlation (P=.02) between expression of Lp(a) in the skin and plasma levels of Lp(a) in patients with LV. ConclusionsIncreased Lp(a) expression in lesional skin of LV patients suggests the role of Lp(a) in the thrombo-occlusive vasculopathy observed in this disease.
- Nodular primary cutaneous melanoma is associated with PD-L1 expression(2020) GIAVINA-BIANCHI, Mara; GIAVINA-BIANCHI, Pedro; SOTTO, Mirian Nacagamo; RODIG, Scott; MIHM JR., Martin; FESTA NETO, Cyro; DUNCAN, Lyn M.; KALIL, JorgeBackground In previous studies, patients with Stage III melanomas expressing PD-L1 in more than 5% of their neoplastic cells had improved recurrence-free survival with anti-PD1 adjuvant therapy. Objectives We examined PD-L1 expression as a possible biomarker of primary cutaneous melanomas in the vertical growth phase. Materials and Methods This was a retrospective study including 66 patients with invasive primary cutaneous melanomas. We assessed patient clinical and histopathological data and performed immunohistochemical assays with melanoma specimens from the patients to evaluate PD-L1, PD-1, CD3, CD8 and FoxP3 expression. Results We observed PD-L1 expression in 21% (14/66) of our samples, and this expression correlated with increased melanoma thickness (p = 0.002) and nodular-type melanoma (p = 0.001). After adjusting for tumor thickness using a logistic regression test, the association of PD-L1 with nodular-type melanoma persisted. Nodular-type melanoma was 6.48 times more likely to be positive for PD-L1 than other histological types (p = 0.014; 95% CI: 1.46-28.82). As expected, PD-L1 expression correlated with the number of PD-1-expressing cells in the tumor-infiltrating lymphocyte population (p = 0.04). No correlation with PD-L1 was observed for age, sex, tumor site, skin phototype, ulceration status, sentinel lymph node status, metastasis development or survival. Regarding the immune profile of the tumor-infiltrating lymphocytes of PD-L1-positive and -negative groups, no significant differences were observed in the numbers of CD3 +, CD8 + FoxP3-, CD8-FoxP3+ and CD8 + FoxP3+ cells by immunohistochemistry. Conclusion Nodular-type melanoma is associated with PD-L1 expression and may be a suitable candidate for adjuvant therapy of primary melanomas treated with immunotherapy.
- Livedoid vasculopathy in 75 Brazilian patients in a single-center institution: Clinical, histopathological and therapy evaluation(2021) CRIADO, Paulo Ricardo; PAGLIARI, Carla; MORITA, Thamara Cristiane Alves Batista; MARQUES, Gabriela Franco; PINCELLI, Thais Prota Hussein; VALENTE, Neusa Yuriko Sakai; GARCIA, Maria Salome Cajas; CARVALHO, Jozelio Freire de; ABDALLA, Beatrice Martinez Zugaib; SOTTO, Mirian NacagamiThis study presents a single center experience with livedoid vasculopathy (LV). A rare disease that can lead to severe quality of life impairment. Characterize clinical data of LV patients at the Dermatology Division at the University of Sao Paulo. A retrospective and transversal study was conducted, from 1 January 2005 to 31 December 2019. About 75 patients diagnosed as LV and confirmed by skin biopsy were included. Epidemiology, clinical appearance, histopathology data, and treatment history were observed. There were 78.66% Caucasian women, with a mean age of 39.9 years. Frequent cutaneous manifestations were ulcers, atrophic blanche-like scars, hyperpigmentation, purpuras, telangiectasias, and livedo racemosa. Pain, pruritus, and hypoesthesia were the main symptoms. After treatment, almost 40% of cases relapsed during spring and summer months. About 66% of cases had thrombophilia factors associated, such as high levels of lipoprotein(a). Frequent treatments included acetylsalicylic acid, pentoxifylline, and diosmin with hesperidin. Not being a prospective study. This research provides useful data on Latin American LV patients, indicating multifactorial conditions involved in LV pathogenesis. An extensive work-up including autoimmune laboratory tests, thrombophilia factors, and other conditions associated with venous stasis should be part of LV investigation and controlled to improve treatment response.
conferenceObject NY-ESO-1 expression is associated with primary cutaneous melanoma thickness(2014) BIANCHI, Mara Giavina; FESTA NETO, Cyro; DUNCAN, Lyn; SOTTO, Miriam- Skin fibrosis associated with keloid, scleroderma and Jorge Lobo's disease (lacaziosis): An immuno-histochemical study(2022) TAFURI, Wagner Luiz; TOMOKANE, Thaise Yumie; SILVA, Ana Maria Goncalves; KANASHIRO-GALO, Luciane; MOSSER, David Miichael; QUARESMA, Juarez Antonio Simoes; PAGLIARI, Carla; SOTTO, Mirian N.Fibrosis is a common pathophysiological response of many tissues and organs subjected to chronic injury. Despite the diverse aetiology of keloid, lacaziosis and localized scleroderma, the process of fibrosis is present in the pathogenesis of all of these three entities beyond other individual clinical and histological distinct characteristics. Fibrosis was studied in 20 samples each of these three chronic cutaneous inflammatory diseases. An immunohistochemical study was carried out to explore the presence of alpha-smooth muscle actin (alpha-SMA) and vimentin cytoskeleton antigens, CD31, CD34, Ki67, p16; CD105, CD163, CD206 and FOXP3 antigens; and the central fibrotic cytokine TGF-beta. Higher expression of vimentin in comparison to alpha-SMA in all three lesion types was found. CD31- and CD34-positive blood vessel endothelial cells were observed throughout the reticular dermis. Ki67 expression was low and almost absent in scleroderma. p16-positive levels were higher than ki67 and observed in reticular dermis of keloidal collagen in keloids, in collagen bundles in scleroderma and in the external layers of the granulomas in lacaziosis. The presence of alpha-actin positive cells and rarely CD34 positive cells, observed primarily in keloids, may be related to higher p16 antigen expression, a measure of cell senescence. Low FOXP3 expression was observed in all lesion types. CD105-positive cells were mainly found in perivascular tissue in close contact with the adventitia in keloids and scleroderma, while, in lacaziosis, these cells were chiefly observed in conjunction with collagen deposition in the external granuloma layer. We did not find high involvement of CD163 or CD206-positive cells in the fibrotic process. TGF-beta was notable only in keloid and lacaziosis lesions. In conclusion, we have suggested vimentin to be the main myofibroblast general marker of the fibrotic process in all three studied diseases, while endothelial-to-mesenchymal transition (EndoMT) and mesenchymal stem cells (MSCs) and M2 macrophages may not play an important role.
- Overexpression of the aryl hydrocarbon receptor in frontal fibrosing alopecia and lichen planopilaris: a potential pathogenic role for dioxins?: an investigational study of 38 patients(2020) DOCHE, I.; PAGLIARI, C.; HORDINSKY, M. K.; WILCOX, G. L.; RIVITTI-MACHADO, M. C. M.; ROMITI, R.; VALENTE, N. Y. S.; SHAIK, J. A.; SALDANHA, M.; SOTTO, M. N.
- Abnormal collagen V deposition in dermis correlates with skin thickening and disease activity in systemic sclerosis(2012) MARTIN, Patricia; TEODORO, Walcy R.; VELOSA, Ana Paula P.; MORAIS, Jymenez de; CARRASCO, Solange; CHRISTMANN, Romy B.; GOLDENSTEIN-SCHAINBERG, Claudia; PARRA, Edwin R.; KATAYAMA, Maria Lucia; SOTTO, Mirian N.; CAPELOZZI, Vera L.; YOSHINARI, Natalino H.Objective: The physiological and mechanical properties of the skin, the primary tissue affected by systemic sclerosis, depend on the assembly of collagen types I, Ill and V, which form heterotypic fibers. Collagen V (COLV) regulates heterotypic fiber diameter, and the maintenance of its properties is important for maintaining normal tissue architecture and function. Based on a COLV-induced experimental SSc model, in which overexpression of abnormal COLV was a prominent feature, we assumed that this abnormality could be present in SSc patients and could be correlated to disease duration, skin thickening and disease activity. Methods: Skin biopsies from 18 patients (6 early-stage and 12 late-stage) and 10 healthy controls were studied. Skin thickening assessment was performed with the Modified Rodnan Skin Score (MRSS), and activity was calculated using the Valentini Disease Activity Index. Morphology, morphometry of COLV deposition in dermis, as well as, quantitative RT-PCR and 3D-reconstruction of the dermal fibroblast culture were performed. Results: Structurally abnormal COLV was overexpressed in SSc skin, mainly in the early stages of the disease, when compared to normal controls and late-stage. A positive correlation between COLV expression and MRSS and disease activity was observed. Collagen V alpha-1 and alpha-2 mRNA expression levels were higher in SSc. Tridimensional reconstruction of SSc dermal heterotypic fibers confirmed the presence of atypical COLV. Conclusion: Increased synthesis of abnormal COLV and its correlation with disease stage, activity and MRSS suggest that this collagen can be a possible trigger involved in the pathogenesis of SSc.
- Immune privilege disruption in folliculotropic mycosis fungoides: investigation of major histocompatibility complex antigen expression(2018) DEONIZIO, Janyana M. D.; GUITART, Joan; YAZDAN, Pedram; MULINARI-BRENNER, Fabiane; SOTTO, Mirian N.; SANCHES, Jose A.BackgroundFolliculotropic mycosis fungoides (FMF) is a cutaneous T-cell lymphoma mainly affecting the hair follicle, which seems to represent a place of immune privilege phenomenon. ObjectivesTo explore a possible role of immune privilege (IP) in FMF analyzing the major histocompatibility complex (MHC) expression. MethodsImmunohistochemistry for HLA-G and MHC-II was performed to formalin-fixed paraffin-embedded cutaneous skin biopsies of FMF patients (n = 43), conventional mycosis fungoides (CMF; n = 13), alopecia areata (AA; n = 13), and normal scalp skin (NS; n = 12). ResultsHLA-G expression was lower in FMF (34%: 14/41) and CMF (18%: 2/11) groups compared to alopecia areata (92%:11/12) and normal scalp skin group (100%: 12/12). MHC-II expression in hair follicle was greater in the FMF group (18/42: 43%) compared to AA (0%) and NS (0%). HLA-G and MHC-II expression in cellular infiltrate had no difference among FMF and CMF groups and was different compared to the AA group. ConclusionsOur data support the hypothesis of disruption of immune privilege based on the lower expression of HLA-G and higher expression of MHC-II in the follicular epithelium in mycosis fungoides compared to alopecia areata and normal scalp skin. The lack of difference between FMF and CMF groups did not support the role of these molecules as a driver of folliculotropism. The expression of MHC molecules seems to be different between neoplastic and inflammatory infiltrates. The definitive significance of expression of the MHC molecules remains unclear, and more studies are necessary to fully understand the role of these molecules in cutaneous lymphomas.
- Upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in renal tissue in severe dengue in humans: Effects on endothelial activation/dysfunction(2019) VITORIA, Webster Oliveira; THOME, Leticia Silva; KANASHIRO-GALO, Luciane; CARVALHO, Leda Viegas de; PENNY, Ricardo; SANTOS, Washington Luis Conrado; VASCONCELOS, Pedro Fernando da Costa; SOTTO, Mirian Nacagami; DUARTE, Maria Irma Seixas; QUARESMA, Juarez Antonio Simoes; PAGLIARI, CarlaIntroduction: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin. and E-selectin to contribute to a better understanding of the pathophysiology of SD. Methods: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. Results: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. Conclusions: The results appear to demonstrate an unbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up. and therapeutic response of patients with SD.