RESUMO
Verrucous carcinoma (VC) is an unusual, well-differentiated, and low-grade type of squamous cell carcinoma, characterized by slow growth, low metastatic spread, local invasion, and little dysplasia. It occurs predominantly on the genitals, in the oropharynx, or in the palmoplantar region, being less frequent at other sites; however, it can occur on any part of the body. Many factors have been associated with its pathogenesis, including the presence of previous skin lesions, such as varicose, decubitus, traumatic, or neuropathic plantar ulcers. VC arising from a burn scar is rare. We report the case of a patient who developed exuberant VC on his knee many years after having burn injuries at that site.
Assuntos
Queimaduras/complicações , Carcinoma Verrucoso/etiologia , Cicatriz/complicações , Neoplasias Cutâneas/etiologia , Carcinoma Verrucoso/patologia , Humanos , Joelho , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologiaRESUMO
Verrucous carcinoma (VC) is an unusual, well-differentiated, and low-grade type of squamous cell carcinoma, characterized by slow growth, low metastatic spread, local invasion, and little dysplasia. It occurs predominantly on the genitals, in the oropharynx, or in the palmoplantar region, being less frequent at other sites; however, it can occur on any part of the body. Many factors have been associated with its pathogenesis, including the presence of previous skin lesions, such as varicose, decubitus, traumatic, or neuropathic plantar ulcers. VC arising from a burn scar is rare. We report the case of a patient who developed exuberant VC on his knee many years after having burn injuries at that site
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Queimaduras/complicações , Cicatriz/complicações , Carcinoma Verrucoso/etiologia , Carcinoma Verrucoso/patologia , JoelhoRESUMO
Lacazia loboi is an uncultivated fungal pathogen of humans and dolphins that causes cutaneous and subcutaneous infections only in the tropical areas of the Americas. It was recently found by phylogenetic analysis that this unusual pathogen is closely related to Paracoccidioides brasiliensis and to the other fungal dimorphic members of the order Onygenales. That original phylogenetic study used universal primers to amplify well-known genes. However, this approach cannot be applied to the study of other proteins. We have developed a strategy for studying the gene encoding the gp43 homologous protein of P. brasiliensis in L. loboi. The gp43 protein was selected because it has been found that this P. brasiliensis antigen strongly reacts when it is used to test sera from patients with lacaziosis. The principle behind this idea was to obtain the gp43 amino acid sequence of P. brasiliensis and other homologous fungal sequences from GenBank and design primers from their aligned conserved regions. These sets of primers were used to amplify the selected regions with genomic DNA extracted from the yeast-like cells of L. loboi from experimentally infected mice. Using this approach, we amplified 483 bp of the L. loboi gp43-like gene. These sequences had 85% identity at the nucleotide level and 75% identity with the deduced amino acid sequences of the P. brasiliensis gp43 protein. The identity of the 483-bp DNA fragment was confirmed by phylogenetic analysis. This analysis revealed that the L. loboi gp43-like deduced amino acid sequence formed a strongly supported (100%) sister group with several P. brasiliensis gp43 sequences and that this taxon in turn was linked to the other fungal sequences used in this analysis. This study shows that the use of a molecular model for investigation of the genes encoding important proteins in L. loboi is feasible.
Assuntos
Antígenos de Fungos/genética , Proteínas Fúngicas/genética , Glicoproteínas/genética , Paracoccidioides/classificação , Paracoccidioides/genética , Sequência de Aminoácidos , Animais , Antígenos de Fungos/química , Proteínas Fúngicas/química , Glicoproteínas/química , Camundongos , Dados de Sequência Molecular , Paracoccidioidomicose/patologia , Filogenia , Reação em Cadeia da PolimeraseRESUMO
Os relatos de resistencia e rifampicina fizeram com que a Organizaçao Mundial de Saude preconizasse, 1981, a poliquimioterapia para o tratamento da hanseniase. A prevençao da seleçao de cepas mutantes resistentes as drogas e um de seus principais objetivos. A dpsona foi a primeira droga a ter comprovação experimental de resistencia e isto so foi possivel depois que a tecnica de inoculaçao do bacilo em coxim plantar de camundongos foi padronizado em 1960. Criterios importantes a serem considerados para se suspeitar de resistencia seriam recidivas em pacientes multibacilares ja tratado, ou em tratamento, ou resposta clinica insatisfatoria. Nosso estudo teve por objetivo detectar cepas resistentes a dapsona e rifampicina entre 40 pacientes tratados com sinais clinicos de recidiva, procedentes de cidades do Estado de Sao paulo e capital, utilizando a tecnica de inoculaçao do em coxim plantar de camundongos. Foram observados bacilos resistentes a dapsona em 11 casos, sendo 05 de resistencia total, 01 intermediario e 05 parcial. Bacilos resistente a rifampicina foram observados em apenas 02 casos. Nao se observou nenhum caso de resistencia multipla. O alto indice obtido de resistencia a dapsona, provavelmente e decorrencia de muitos anos de monoterapia sulfonica ou de seus derivados. No caso da rifampicina, provavelmente a droga foi utilizada de forma irregular, em monoterapia ou aind, o paciente pode ter utilizado-a previamente para tratar outra molestia....
Assuntos
Mycobacterium leprae , Hanseníase/tratamento farmacológico , Hansenostáticos/uso terapêutico , Modelos Animais , Hanseníase/patologiaRESUMO
Few studies have been conducted to evaluate the cellular composition of the granulomatous lesions induced by Lacazia loboi. Thus, the objective of the present study was to characterize the mononuclear cell population present in cutaneous lesions obtained from 15 patients with Jorge Lobo's disease. Histological sections were stained with hematoxylin-eosin and methenamine silver and the following mononuclear cells were identified by immunohistochemistry: T lymphocytes (CD3+), helper T lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), B lymphocytes (CD20+), plasma cells (CD79+), natural killer cells (CD57+) and histiocytes (CD68+). This study showed that the inflammatory infiltrate mainly consists of histiocytes and multinucleated giant cells, in addition to the presence of a large number of fungal cells. The identified inflammatory cells showed the following frequency: CD68+ histiocytes > CD3+ T lymphocytes > CD4+ T > CD8+ T lymphocytes > CD57+ natural killer cells > CD79+ plasma cells > CD20+ B lymphocytes. Based on the findings of a large number of fungal cells in the infected tissues and the disorganized cell arrangement in the granuloma, we hypothesize that patients with Jorge Lobo's disease present immunoregulatory disturbances, which are likely to be specific and perhaps responsible for the lack of containment of the pathogen.
Assuntos
Dermatomicoses/patologia , Células Gigantes/patologia , Granuloma/patologia , Subpopulações de Linfócitos/patologia , Fungos Mitospóricos/isolamento & purificação , Onygenales/isolamento & purificação , Plasmócitos/patologia , Antígenos CD/análise , Brasil , Dermatomicoses/imunologia , Dermatomicoses/microbiologia , Granuloma/imunologia , Granuloma/microbiologia , Interações Hospedeiro-Parasita , Humanos , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Fungos Mitospóricos/imunologia , Onygenales/imunologia , Pele/patologia , Subpopulações de Linfócitos T/patologiaRESUMO
Lacazia loboi is an uncultivated fungal pathogen of humans and dolphins that causes cutaneous and subcutaneous infections only in the tropical areas of the Americas. It was recently found by phylogenetic analysis that this unusual pathogen is closely related to Paracoccidioides brasiliensis and to the other fungal dimorphic members of the order Onygenales. That original phylogenetic study used universal primers to amplify well-known genes. However, this approach cannot be applied to the study of other proteins. We have developed a strategy for studying the gene encoding the gp43 homologous protein of P. brasiliensis in L. loboi. The gp43 protein was selected because it has been found that this P. brasiliensis antigen strongly reacts when it is used to test sera from patients with lacaziosis. The principle behind this idea was to obtain the gp43 amino acid sequence of P. brasiliensis and other homologous fungal sequences from GenBank and design primers from their aligned conserved regions. These sets of primers were used to amplify the selected regions with genomic DNA extracted from the yeast-like cells of L. loboi from experimentally infected mice. Using this approach, we amplified 483 bp of the L. loboi gp43-like gene. These sequences had 85% identity at the nucleotide level and 75% identity with the deduced amino acid sequences of the P. brasiliensis gp43 protein. The identity of the 483-bp DNA fragment was confirmed by phylogenetic analysis. This analysis revealed that the L. loboi gp43-like deduced amino acid sequence formed a strongly supported (100%) sister group with several P. brasiliensis gp43 sequences and that this taxon in turn was linked to the other fungal sequences used in this analysis. This study shows that the use of a molecular model for investigation of the genes encoding important proteins in L. loboi is feasible.
Assuntos
Animais , Camundongos , Paracoccidioides/genética , Paracoccidioidomicose/patologia , Filogenia , Proteínas Fúngicas/genética , Proteínas Fúngicas/química , Dados de Sequência Molecular , Glicoproteínas/genética , Glicoproteínas/química , Reação em Cadeia da Polimerase , Sequência de Aminoácidos , Antígenos de Fungos/genética , Antígenos de Fungos/químicaRESUMO
Few studies have been conducted to evaluate the cellular composition of the granulomatous lesions induced by Lacazia loboi. Thus, the objective of the present study was to characterize the mononuclear cell population present in cutaneous lesions obtained from 15 patients with Jorge Lobo's disease. Histological sections were stained with hematoxylin-eosin and methenamine silver and the following mononuclear cells were identified by immunohistochemistry: T lymphocytes (CD3+), helper T lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), B lymphocytes (CD20+), plasma cells (CD79+), natural killer cells (CD57+) and histiocytes (CD68+). This study showed that the inflammatory infiltrate mainly consists of histiocytes and multinucleated giant cells, in addition to the presence of a large number of fungal cells. The identified inflammatory cells showed the following frequency: CD68+ histiocytes > CD3+ T lymphocytes > CD4+ T > CD8+ T lymphocytes > CD57+ natural killer cells > CD79+ plasma cells > CD20+ B lymphocytes. Based on the findings of a large number of fungal cells in the infected tissues and the disorganized cell arrangement in the granuloma, we hypothesize that patients with Jorge Lobo's disease present immunoregulatory disturbances, which are likely to be specific and perhaps responsible for the lack of containment of the pathogen
Considerando la escasez de estudios sobre la composición celular del granuloma inducido por el Lacazia loboi y el pequeño número de pacientes evaluados, hemos estudiado la población de células mononucleares presentes en las lesiones cutáneas de 15 pacientes portadores de la enfermedad de Jorge Lobo. Se tiñeron los cortes histológicos con hematoxilina-eosina, plata metenamina y con el método imunohistoquímico se identificaron las siguientes células mononucleares: linfocitos T (CD3+), linfocitos T auxiliares (CD4+), linfocitos T citotóxicos (CD8+), linfocitos B (CD20+), plasmócitos (CD79+), células NK (CD57+) e histiocitos (CD68+). Los resultados obtenidos revelaron que el infiltrado inflamatorio estaba compuesto predominantemente por histiocitos y células gigantes multinucleadas, además de un gran número de hongos. La frecuencia de células encontradas fue la siguiente: histiocitos CD68+ > linfocitos T CD3+ > linfocitos T CD4+ > linfocitos T CD8+ > células NK CD57+ > plasmocitos CD79+ > linfocitos B CD20+. Así, considerando los resultados obtenidos, en los que observamos una gran cantidad de hongos en las lesions y una disposición desorganizada de las células en el granuloma, podemos sugerir que los pacientes con la enfermedad de Jorge Lobo presentan alteraciones imunorregulatorias, probablemente específicas, responsables de la no contención del patógeno
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Células Matadoras Naturais/patologia , Dermatomicoses/imunologia , Dermatomicoses/microbiologia , Fungos Mitospóricos/imunologia , Granuloma/imunologia , Granuloma/microbiologia , Interações Hospedeiro-Parasita , Onygenales/imunologia , Pele/patologia , Subpopulações de Linfócitos T/patologia , Dermatomicoses/patologia , Fungos Mitospóricos/isolamento & purificação , Granuloma/patologia , Onygenales/isolamento & purificação , Plasmócitos/patologia , Subpopulações de Linfócitos/patologiaRESUMO
Os autores apresentam o caso de uma crianca de 8 anos, portadora de aids por transmissao vertical, que desenvolveu as primeiras manifestacoes da hanseniase tuberculoide, antes do inicio do tratamento anti-retroviral. As lesoes iniciais percebidas eram ulceras de bordas endurecidas, que cicatrizavam e ulceravam novamente. Nesta epoca apresentava 0,3 celulas CD4+. As lesoes permaneceram com esta evolucao ate o momento em que foram realizados os primeiros exames para confirmacao do diagnostico de hanseniase. Nesta ocasiao estava fazendo tratamento anti-retroviral, apresentava 270 celulas CD4+. Foi realizada uma biopsia da lesao cutanea. Quando retornou, as ulceras estavam cicatrizadas, podendo se notar mais nitidamente o aspecto sarcoidico das lesoes. A reacao de Mitsuda foi de 8,5mm, havia hipoestesia em perna esquerda, e o diagnostico de hanseniase foi definido, principalmente atraves da imunoistoquimica anti-proteina S100, que demonstrou fragmentos de ramos nervosos no interior dos granulomas. A incidencia da hanseniase nao aumentou com o advento da aids e tambem nao ha modificacoes na apresentacao clinica, nem resposta a terapeutica nos casos de hanseniase associado a aids. Tambem nao observamos neste paciente o desenvolvimento da reacao tipo 1, como resultado da reconstituicao imunologica em decorrencia do tratamento anti-retroviral
Assuntos
Hanseníase Tuberculoide , Síndrome da Imunodeficiência AdquiridaRESUMO
Few studies are available about the participation of the immune response in the control or the development of Jorge Lobo's disease. Thus, the objective of the present study was to quantify macrophage and lymphocyte cytokines in the supernatant of cell cultures and in blood serum from patients with this disease. The study was conducted on 15 patients with the mycosis and on 15 healthy adult individuals (control group). Blood samples were collected in order to obtain serum and mononuclear cells. Monocytes were cultured for 24 h in the presence or absence of LPS and L. loboi, and lymphocytes were cultured for 48 h in the presence or absence of PHA and L. loboi. Cytokines IL-1beta, TNF-alpha and IL-6 were quantified by ELISA in the supernatants of monocyte cultures and in serum. Cytokines IL-2, IFN-gamma, IL-4 and IL-10 were quantified by FLISA in the supernatants of lymphocyte cultures and in serum. The quantification of the cytokines in the culture supernatant revealed a greater IL-4 and IL-6 production and lower IL-2 levels in patients compared to control. The production of IL-1beta, TNF-alpha, IL-10 and INF-gamma was similar in patients and controls. The mononuclear cells from patients with the non-localized form of the disease produced higher INF-gamma levels than those of patients with the localized form. The results suggest that patients with Jorge Lobo's disease show altered cytokine profiles represented by a predominance of the Th2 profile. However, further studies are needed to assess the participation of cytokines in the cell-fungus interaction in situ.
Assuntos
Citocinas/imunologia , Dermatomicoses/imunologia , Fungos/imunologia , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Citocinas/sangue , Dermatomicoses/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , População Rural , Estatísticas não Paramétricas , Células Th2/imunologiaRESUMO
E apresentado um caso de hanseniase pre-dimorfa tratada com PQT/PB/OMS com alguma melhora na ocasiao da alta. Um ano apos, a area de anestesia que apresentava no dorso do pe direito se estendeu pela panturrilha ate o cavo popliteo. Seis anos depois paciente retorna ao Centro de Saude com lesoes em placa quase planas roseo-hipocromicas anestesicas no tronco e pe esquerdo. Uma biopsia de uma lesao do abdome mostrou um quadro histopatologico compativel com reacao tipo 1 e baciloscopia igual a +++. Oa autores discutem a possibilidade dos bacilos estatem em um estado de persistencia e nao terem sido destruidos pelas drogas utilizadas. Segundo eles, apos a alta houve progressao dos bacilos pelos nervos determinando alteracoes no seu microambiente e consequentemente causando aumento da area anestesica sem serem reconhecidos ainda pelo sistema imune. Quando 6 anos depois eles se multiplicaram e foram finalmente reconhecidos pelas defesas do organismo, foram em parte destruidos, e deram lugar ao aparecimento de antigenos que desencadearam uma reacao de hipersensibilidade (reacao tipo 1). Os autores chamam a atencao que esses fatos tem que ser levados em consideracao no tratamento de pacientes nessas condicoes porque a resposta ao tratamento dos casos paucibacilares e diferente dos casos virchovianos
Assuntos
Hanseníase Dimorfa/classificação , Hanseníase Dimorfa/imunologia , Hanseníase Dimorfa/patologia , Hanseníase Dimorfa/tratamento farmacológicoRESUMO
Studies on host-parasite interaction in Jorge Lobo's disease are scarce, with no report in the literature on the phagocytosis of Lacazia loboi by phagocytic mononuclear cells. Thus, the objective of the present study was to assess the phagocytic activity of blood monocytes in the presence of L. loboi in patients with the disease and in healthy subjects (controls) over 3 and 24 hours of incubation. Statistical analyses of the results showed no significant difference in percent phagocytosis of the fungus between patient and control monocytes. With respect to incubation time, however, there was a significant difference, in that percent phagocytosis was higher at 3 hours than at 24 hours (p <0.01). These results suggest that monocytes from patients with the mycosis are able to phagocyte the fungus, as also observed in control individuals.
Assuntos
Dermatomicoses/sangue , Fungos , Monócitos/fisiologia , Fagocitose/fisiologia , Análise de Variância , Estudos de Casos e Controles , Humanos , Monócitos/microbiologia , Fatores de TempoRESUMO
Os estudos envolvendo a interação hospedeiro-parasita na doença de Jorge Lobo são escassos; até o momento, não existe nenhum trabalho abordando a fagocitose do fungo Lacazia loboi pelas células mononucleares fagocitárias. Assim, o presente estudo teve como objetivo avaliar a atividade fagocítica dos monócitos sangüíneos frente ao L. loboi tanto em pacientes portadores da doença como em indivíduos sadios (grupo controle), utilizando 3 e 24 horas de incubação. A análise estatística dos resultados revelou que não houve diferença significante entre o percentual de fagocitose do fungo pelos monócitos de pacientes e do grupo controle, porém em relação aos tempos de incubação, houve diferença significante, isto é, às 3 horas o percentual de fagocitose foi maior que o obtido às 24 horas (p<0,01). Estes resultados sugerem que monócitos de pacientes portadores da micose são hábeis em fagocitar o fungo, à semelhança do que foi visto em indivíduos do grupo controle.