RESUMO
Staphylococcus aureus is involved in a wide variety of diseases in humans and animals, and it is considered one of the most significant etiological agents of intramammary infection in dairy ruminants, causing both clinical and subclinical infections. In this study, the intra-farm prevalence and circulation of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) were investigated on an Italian dairy sheep farm previously identified as MRSA-positive by testing bulk tank milk (first isolation in 2012). Human samples (nasal swabs, hand skin samples, and oropharyngeal swabs) from 3 persons working in close contact with the animals were also collected, and the genetic characteristics and relatedness of the MRSA isolates from human and animal sources within the farm were investigated. After 2yr from the first isolation, we confirmed the presence of the same multidrug-resistant strain of MRSA sequence type (ST)1, clonal complex (CC)1, spa type t127, staphylococcal cassette chromosome mec (SCCmec) type IVa, showing identical pulsed field gel electrophoresis (PFGE) and resistance profiles at the farm level in bulk tank milk. Methicillin-resistant S. aureus isolates were detected in 2 out of 556 (0.34%) individual milk samples, whereas MSSA isolates were detected in 10 samples (1.8%). The MRSA were further isolated from udder skin samples from the 2 animals that were MRSA-positive in milk and in 2 of the 3 examined farm personnel. All MRSA isolates from both ovine and human samples belonged to ST(CC)1, spa type t127, SCCmec type IVa, with some isolates from animals harboring genes considered markers of human adaptation. In contrast, all MSSA isolates belonged to ruminant-associated CC130, ST700, spa type t528. Analysis by PFGE performed on selected MRSA isolates of human and animal origin identified 2 closely related (96.3% similarity) pulsotypes, displaying only minimal differences in gene profiles (e.g., presence of the immune evasion cluster genes). Although we observed low MRSA intra-farm prevalence, our findings highlight the importance of considering the possible zoonotic potential of CC1 livestock-associated MRSA, in view of the ability to persist over years at the farm level. Biosecurity measures and good hygiene practices could be useful to prevent MRSA spread at the farm level and to minimize exposure in the community and in categories related to farm animal industry (e.g., veterinarians, farmers, and farm workers).
Assuntos
Resistência a Meticilina , Staphylococcus aureus/isolamento & purificação , Animais , Antibacterianos/farmacologia , Fazendas , Humanos , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Ovinos , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/efeitos dos fármacosRESUMO
Trifluoperazine, a drug that binds to Ca2+-calmodulin and inhibits its interaction with other proteins, was found to inhibit growth and phagocytosis in a macrophagelike cell line, J774.16. Both effects were reversible and occurred at the same concentrations of drug (25--50 microM) that inhibited the activation of cyclic nucleotide phosphodiesterase by calmodulin in vitro. Fc-mediated phagocytosis was also depressed by W-7, a sulfonamide derivative that inhibits the activity of Ca2+-calmodulin. In contrast, taxol, a drug that stabilizes cellular microtubules, had no effect on Fc-mediated phagocytosis although it inhibited cell growth at nanomolar concentrations. The inhibitory effects of trifluoperazine and W-7 on phagocytosis suggest that calmodulin may be involved in this complex cellular function.
Assuntos
Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Calmodulina/antagonistas & inibidores , Macrófagos/fisiologia , Fagocitose/efeitos dos fármacos , Trifluoperazina/farmacologia , Alcaloides/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Muramidase/metabolismo , Paclitaxel , Sulfonamidas/farmacologiaRESUMO
This study was conducted to determine the impact of polycystic ovary syndrome and ethnicity on insulin action. Thirteen Caribbean-Hispanic and 10 non-Hispanic white polycystic ovary syndrome women were compared with 5 Caribbean-Hispanic and 8 non-Hispanic white normal women matched for age, weight, and body composition. All subjects underwent a 2-h 75 g oral glucose tolerance test and euglycemic glucose clamp study with a 40 mU.m-2 x min-1 insulin dose. Hepatic glucose production was determined basally and throughout the euglycemic clamp study. Polycystic ovary syndrome was associated with significant increases in fasting insulin levels (P < 0.05) and in 2-h postglucose-load glucose and insulin levels (P < 0.001). Ethnicity was not associated with any changes in these parameters. Polycystic ovary syndrome but not ethnicity was also associated with hepatic insulin resistance, because significant (P < 0.05) residual hepatic glucose production occurred during the euglycemic clamp in the polycystic ovary syndrome women. However, significant independent effects existed for both polycystic ovary syndrome (P < 0.01) and ethnicity (P < 0.05) that resulted in decreased insulin-mediated glucose disposal. Similarly, significant independent effects of polycystic ovary syndrome (P < 0.005) and ethnicity (P < 0.05) occurred, resulting in increased steady-state insulin levels during the euglycemic clamp. This appeared to be, in part, secondary to a decrease in the metabolic clearance rate of insulin associated with ethnicity (P < 0.05). We conclude that polycystic ovary syndrome and ethnicity result in independent and additive decreases in insulin sensitivity in Caribbean-Hispanic women.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hispânico ou Latino , Resistência à Insulina/fisiologia , Síndrome do Ovário Policístico/etnologia , Adolescente , Adulto , Análise de Variância , Androstenodiona/sangue , Glicemia/análise , Composição Corporal , Peso Corporal , República Dominicana/etnologia , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Lipídeos/análise , Taxa de Depuração Metabólica , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/fisiopatologia , Porto Rico/etnologia , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Estados Unidos/epidemiologiaRESUMO
Emerging evidence suggests that apoptosis is an important mechanism of tumor cell death from antineoplastic therapy. 7-hydroxystaurosporine (UCN-01) is a novel protein kinase inhibitor that increases chemotherapy-induced apoptosis in vitro and is in early phases of clinical development. In this report, we present a 68-year-old patient with chemotherapy-resistant lymphoma treated with UCN-01 and chemotherapy. He had a stage IV plasmacytoid lymphoma that failed to enter remission with high-dose EPOCH II (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) chemotherapy. Due to disease progression and transformation to large cell lymphoma in the liver and bone marrow, he received UCN-01. Four weeks later, he received "standard-dose" EPOCH because of progression, developed severe neutropenia for 9 days, and expired from Candida sepsis on day 23. At autopsy, there was no histological evidence of residual lymphoma, although PCR for immunoglobulin gene rearrangement analysis revealed a faint clonal band in two of six nodes but none in the liver. Significantly, no B cells were detected by immunohistochemistry in lymph nodes, and a polyclonal ladder pattern associated with the presence of normal B cells was not seen in the immunoglobulin gene rearrangement PCR assay. Profound peripheral lymphopenia (50 cells/microliter) was also observed. Pharmacokinetics showed UCN-01 salivary concentrations, a surrogate for free drug concentrations, to be within an effective range in vitro (45 nmol/L) as a modulator of DNA-damaging agent cytotoxicity. In vitro, UCN-01 is synergistic with multiple cytotoxic agents and increases fludarabine-induced apoptosis in a human breast cell line. These results suggest that UCN-01 sensitized the lymphoma to the cytotoxic effects of EPOCH, possibly by modulating the "threshold" for apoptosis, and may illustrate a new paradigm for reversal of drug resistance.
Assuntos
Alcaloides/uso terapêutico , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Linfoma de Células B/tratamento farmacológico , Proteína Quinase C/antagonistas & inibidores , Idoso , Alcaloides/farmacocinética , Antineoplásicos/farmacocinética , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Humanos , Linfonodos/patologia , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Masculino , Estadiamento de Neoplasias , Estaurosporina/análogos & derivados , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Distribuição TecidualRESUMO
The existence of primary nodal marginal zone lymphomas (MZL) is controversial, as is their relationship to putative extranodal counterparts. Most nodal lymphomas with monocytoid B cell/marginal zone differentiation exhibit the morphologic and immunophenotypical characteristics of extranodal MALT-lymphomas. Splenic marginal zone lymphoma (SMZL) is also of putative marginal zone derivation, but it differs immunophenotypically from MALT lymphoma. To clarify the relationship between nodal and extranodal MZLs and to investigate the possible existence of a nodal variant of SMZL, 36 MZL initially considered to be primary nodal neoplasms were examined. Other low-grade lymphomas with marginal zone differentiation were excluded (small lymphocytic lymphoma/chronic lymphocytic leukemia [SLL/CLL], follicular lymphoma, and mantle cell lymphoma). Six nodal MZLs showed morphologic and phenotypic characteristics similar to those of SMZL, whereas 30 tumors were more similar to MALT-type lymphomas. The six tumors with SMZL features showed a polymorphic infiltrate surrounding residual germinal centers with absent or very attenuated mantle cuffs. These lymphomas were IgD positive (6/6) but cyclin D1 (0/5), CD5 (0/6), and CD23 (0/6) negative. Five of these patients came for treatment in stage I or II. No patient manifested splenomegaly, peripheral blood, and/or bone marrow infiltration either at diagnosis or during follow-up. Lymph nodes from 30 patients with MALT-type features showed a perisinusoidal and perivascular infiltration of monocytoid/centrocytoid cells and residual germinal centers with a relatively well-preserved mantle cuff. The neoplastic cells were negative for IgD (0/17), cyclin D1 (0/8), and CD5 (0/12). Seven of 16 (44%) patients with a detailed history and clinical follow-up had evidence of extranodal lymphoma. These observations suggest that most nodal B cell lymphomas with marginal zone differentiation are of the MALT type and that they are frequently associated with an extranodal component. In addition, a primary nodal counterpart of splenic MZL also exists, and may occur in the absence of splenomegaly.
Assuntos
Linfonodos/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Células B/patologia , Neoplasias Esplênicas/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , DNA de Neoplasias/análise , Feminino , Humanos , Imunofenotipagem , Linfoma de Células B/química , Linfoma de Células B/genética , Linfoma de Zona Marginal Tipo Células B/química , Linfoma de Zona Marginal Tipo Células B/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Neoplasias Esplênicas/química , Neoplasias Esplênicas/genéticaRESUMO
Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive Epstein-Barr virus-associated B-cell lymphoproliferative disorder (EBV-BLPD), varying widely from an indolent process to an aggressive large cell lymphoma. The skin is the extrapulmonary organ most commonly involved in LYG. We studied 32 skin lesions from 20 patients with known pulmonary LYG, using immunohistochemistry, in situ hybridization for EBV, and polymerase chain reaction for the presence of antigen receptor gene rearrangements (IgH and TCR) to better define both the clinicopathologic spectrum and pathogenesis of the cutaneous lesions. We describe two distinct patterns of cutaneous involvement. Multiple erythematous dermal papules and/or subcutaneous nodules, with or without ulceration, were present in 17 patients (85%). These lesions demonstrate a marked angiocentric lymphohistiocytic infiltrate, composed predominantly of CD4-positive T-cells, with a high propensity for involving the subcutaneous tissues, and exhibiting angiodestruction, necrosis, and cytologic atypia. EBV-positive B-cells were detected in the nodules from five patients; clonal immunoglobulin heavy chain gene (IgH) rearrangements were detected by polymerase chain reaction in two patients. Multiple indurated, erythematous to white plaques were present in three patients (15%). The plaque lesions were negative for EBV and clonal IgH gene rearrangements in all cases studied. The clinical course of overall disease was variable, ranging from spontaneous regression without treatment (1 of 13; 7%), resolution with chemo/immunomodulatory therapy (8 of 13; 62%), and progression (4 of 13; 31%). The clinical and histopathologic features of cutaneous LYG are extremely diverse. However, the majority (85%) of the cutaneous lesions mirrors to some extent LYG in the lung, although EBV+ cells are less frequently identified. This subset of cases shows the histopathologic triad of angiodestruction with associated necrosis, panniculitis, and in some cases atypical lymphoid cells. The commonality of the histologic features in this group suggests a common pathophysiologic basis, possibly mediated by cytokines and chemokines induced by EBV. A small percentage of the lesions (15%) presented as indurated and atrophic plaques, and EBV was not identified in the small number of cases studied. The relationship of the plaque-like lesions to LYG remains uncertain. Whereas some cases of LYG regress spontaneously, most require therapy.
Assuntos
Granulomatose Linfomatoide/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Linfócitos B/metabolismo , Linfócitos B/patologia , Células Clonais , DNA de Neoplasias/análise , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/patologia , Feminino , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Hibridização In Situ , Granulomatose Linfomatoide/genética , Granulomatose Linfomatoide/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/análise , Receptores de Antígenos de Linfócitos T gama-delta/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/virologia , Linfócitos T/metabolismo , Linfócitos T/patologiaRESUMO
Inflammatory bowel disease (IBD) is associated with an increased risk of lymphoma, which is usually extraintestinal but sometimes may involve the diseased bowel itself. Most lymphomas described in this setting are of non-Hodgkin's type, but rare cases of Hodgkin's disease (HD) have been reported. We describe the clinicopathologic and molecular features of four patients with primary gastrointestinal HD. Three patients had preexistent Crohn's disease (CD), for which two of them had received immunosuppressive therapy. The fourth patient had a longstanding history of diverticulitis and myasthenia gravis and was receiving immunosuppressive therapy for the latter. Multifocal involvement of the bowel by HD was noted in all four cases. Disease was staged as IVA in one patient, IIIB in one patient, and IE in one patient, and the fourth patient died in the postoperative period before further workup. Two patients received chemotherapy, one of whom was dead at 9 months, whereas the other has no evidence of disease at 25 months' follow-up. The patient with IE disease did not receive any therapy because only a few microscopic foci of disease were present and is also without any evidence of disease at 17 months. The Reed-Sternberg (RS) cells in all four cases expressed CD30, CD15, EBER-1, and LMP-1; two of four were focally CD20-positive. VJ-polymerase chain reaction for immunoglobulin heavy chain (IgH) rearrangement showed a polyclonal pattern in all four cases. In two cases, laser capture microdissection was used to isolate individual RS and Hodgkin's cells, which contained rearranged immunoglobulin genes, confirming a B-cell genotype. Whereas one case showed a dominant clonal band present in all isolates, cells from the patient with stage IE disease clearly showed a polyclonal population of RS cells. Our findings indicate that HD arising in the setting of IBD or chronic inflammation is the result of an Epstein-Barr virus-driven lymphoproliferation, analogous to that found in other immunodeficient states. Disordered immunoregulation inherent to CD and immunosuppressive therapy for the latter may contribute to its development. The finding of polyclonal RS cells in a patient with early stage disease and apparent cure by surgical resection versus monoclonal RS cells in the patient with disseminated disease suggests that HD in the setting of immunodeficiency also may show molecular progression, in a manner similar to that occurring in conventional B-cell lymphoproliferative disorders arising in the same setting.
Assuntos
Neoplasias do Colo/patologia , Doença de Crohn/complicações , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/complicações , Neoplasias do Íleo/patologia , Terapia de Imunossupressão/efeitos adversos , Adulto , Idoso , Biópsia , Colectomia , Colo/patologia , Colo Sigmoide/patologia , Neoplasias do Colo/etiologia , Neoplasias do Colo/cirurgia , Doença de Crohn/patologia , Feminino , Seguimentos , Herpesvirus Humano 4/genética , Doença de Hodgkin/patologia , Doença de Hodgkin/cirurgia , Humanos , Neoplasias do Íleo/etiologia , Neoplasias do Íleo/cirurgia , Íleo/patologia , Imunofenotipagem , Hibridização In Situ , Metástase Linfática , Masculino , Reação em Cadeia da Polimerase , Células de Reed-Sternberg , Fatores de TempoRESUMO
Subcutaneous panniculitic T cell lymphoma (SCPTCL) is characterized by primary involvement of the subcutaneous fat in a manner mimicking panniculitis. We studied 16 cases of this lymphoma to define its immunophenotypical profile as well as cellular origin. Involvement of the subcutaneous fat in a lacelike pattern with neoplastic cells rimming individual fat spaces was present in all cases. All 16 cases were of T cell phenotype. Thirteen of the 16 cases were CD8+, whereas three were negative for both CD4 and CD8. Twelve cases were stained for betaF1; of these, eight were betaF1+ and four were betaF1-. Focal staining for CD56 and CD30 was seen in 2 of 13 and two of eight cases, respectively. Intense diffuse positivity for the cytotoxic granular proteins T cell intracellular antigen-1 (TIA-1) and perforin was present in all cases, indicating an origin from cytotoxic T lymphocytes. Ten cases studied for Epstein-Barr viral sequences were negative. Eight of 9 cases with amplifiable DNA showed a clonal TCR gamma gene rearrangement by polymerase chain reaction. Controls included seven cases of benign panniculitis and seven other peripheral T cell lymphomas involving the skin and subcutaneous tissues: two peripheral T cell lymphomas, not otherwise specified (PTL,NOS), four anaplastic large cell lymphomas (ALCL), one T/NK cell lymphoma. The seven cases of panniculitis lacked cytological atypia and were characterized by an admixture of CD4+ and CD8+ cells with interspersed aggregates of L26+ B cells. Only infrequent cells showed staining for TIA-1 and perforin. In the control cases of T cell lymphoma, the infiltrate had a tendency for dermal and sometimes even epidermal involvement, with sheeting out of malignant cells, in contrast to the characteristic subcutaneous localization and rimming of fat spaces noted in SCPTCL. The two PTL, NOS were CD4+ and negative for both TIA-1 and perforin. Although the remaining controls expressed TIA-1 and perforin, in keeping with their cytotoxic T or natural killer (NK) cell origin, histological and other immunophenotypical features allowed distinction from SCPTCL. Five cases of SCPTCL were also stained for apoptosis using a tdt-mediated end labeling kit. All cases showed numerous positive apoptotic bodies, suggesting apoptosis as the mechanism of cell death in these tumors. Our study indicates that SCPTCL constitutes a distinctive clinicopathological entity derived from cytotoxic T lymphocytes and should be differentiated from other benign and malignant lymphoid infiltrates involving the subcutis. The apoptosis seen in these tumors may be mediated by release of cytotoxic granular proteins.
Assuntos
Linfoma Cutâneo de Células T/patologia , Paniculite/imunologia , Paniculite/patologia , Proteínas , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Linfócitos T Citotóxicos/patologia , Adulto , Antígenos CD/análise , Apoptose , DNA de Neoplasias/análise , Feminino , Fator Estimulador de Colônias de Granulócitos/análise , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização In Situ , Lactente , Linfoma Cutâneo de Células T/química , Masculino , Glicoproteínas de Membrana/análise , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Perforina , Proteínas de Ligação a Poli(A) , Reação em Cadeia da Polimerase , Proteínas Citotóxicas Formadoras de Poros , Proteínas de Ligação a RNA/análise , Receptores de Antígenos de Linfócitos T/genética , Neoplasias Cutâneas/química , Antígeno-1 Intracelular de Células T , Linfócitos T Citotóxicos/químicaRESUMO
Women with polycystic ovary syndrome (PCOS) are markedly insulin-resistant, but the molecular mechanisms of these changes and their relationship to the hyperandrogenic state remain to be clarified. Mutations have recently been identified in the insulin receptor gene of patients with extreme forms of insulin resistance associated with hyperandrogenism (eg, type A insulin resistance), and these mutations account for the insulin resistance in such patients. We performed this study to determine whether mutations in the coding portion of the insulin receptor gene were responsible for insulin resistance in PCOS. Insulin binding studies using cultured skin fibroblasts of three obese (body mass index > 27 kg/m2) women with PCOS (ie, mild hyperandrogenemia and chronic anovulation of unknown etiology) and documented insulin resistance showed no apparent abnormalities in either the number or affinity of insulin binding sites. Direct sequencing of all 22 exons of the insulin receptor gene from two of the women with PCOS did not reveal any mutations. Furthermore, both alleles of the gene were expressed at equal levels. In a third insulin-resistant PCOS woman, there was no evidence for a mutation in the coding portion of the insulin receptor gene as determined by denaturing gradient gel electrophoresis (DGGE). We conclude that the insulin resistance in these PCOS women was caused by a defect extrinsic to the insulin receptor.
Assuntos
Resistência à Insulina/genética , Mutação , Síndrome do Ovário Policístico/genética , Receptor de Insulina/genética , Adulto , Sequência de Bases , Células Cultivadas , Eletroforese em Gel de Poliacrilamida , Feminino , Fibroblastos/metabolismo , Humanos , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Síndrome do Ovário Policístico/fisiopatologia , Reação em Cadeia da Polimerase , Pele/citologiaRESUMO
An increased incidence of intermediate to high-grade Non Hodgkin's Lymphoma is found in individuals with AIDS. Although immune function in AIDS patients can be improved through the use of antiretroviral therapy, the contribution of these drugs to lymphoma regression is not known. Here we describe the complete regression and subsequent recurrence of high grade, Burkitt-like lymphoma during antiretroviral therapy in a patient with AIDS. Antiretroviral therapy resulted in diminished viral load and modest improvement in CD4+ T cell counts. Lymphoma regressed initially, but relapsed 3 months later. Tissue taken from the initial and recurrent tumor demonstrated different clonal rearrangements. The recurrent lymphoma did not respond to continued antiretroviral therapy. In Conclusion, antiretroviral therapy may contribute to lymphoma regression in AIDS lymphoma. Clinically recurrent disease may be clonally distinct.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/patologia , Adulto , Linfoma de Burkitt , Células Clonais/patologia , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Masculino , Segunda Neoplasia Primária/patologia , Recidiva , Indução de RemissãoRESUMO
Epstein-Barr virus (EBV) associated with lymphoid neoplasms demonstrates preferential association with certain viral strains. Previous subtyping studies have however been confined to analysis of sequence variability within a single locus in EBV. Variations have now been reported for several latently expressed EBV genes, including, EBNAs-1, 2 and LMP-1. Variant EBNA-1 strains have been identified in Burkitt's lymphomas and clustering of subtypes for LMP and EBNA-2 have been associated with either malignancy and/or clinical disease. To investigate the linkage between the variability in these three loci in EBV associated with lymphoid malignancies, we subclassified EBV-associated lymphoproliferations (9 reactive and 24 malignant) from HIV-negative and HIV-positive patients by analysis of the EBNA-1, LMP1, and EBNA-2 genes. Our results demonstrate that (1) EBV identical to the prototype B95.8 strain (Type 1 EBNA-2, wild type EBNA-1 and LMP-1) is very rarely associated with tumors. (2) The EBNA-1 variant V-leucine, restricted to malignant lymphomas in immunocompetent patients, was readily identified in non-malignant lesions in HIV infected patients. (3) Variations of EBNA-1 occur independent of variations at other loci.
Assuntos
Soronegatividade para HIV , Soropositividade para HIV/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Linfoma/virologia , Antígenos Virais/genética , Linfoma de Burkitt/genética , Linfoma de Burkitt/virologia , Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/genética , Marcadores Genéticos , Genótipo , Soronegatividade para HIV/genética , Soropositividade para HIV/genética , Humanos , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/virologiaRESUMO
Lymphoproliferative disorder of granular lymphocytes (LDGL) is a low grade T-cell disease characterized by clonal expansion of large granular lymphocytes of either T cell or natural killer (NK) cell lineage that express the cytotoxic T-cell/NK cell antigens CD16, CD56 and/or CD57. LDGL has been described in association with other malignancies, leading to theories of a common abnormal stem cell as well as development of the LDGL as an immune response to a primary tumor. We have studied 32 patients with hairy cell leukemia (HCL). In 15 patients (47%) we detected an increase in cells expressing cytotoxic T-cell/NK cell antigens. In 10(31%) patients these cells were of T cell lineage, while 5 patients (16%) had increased NK-cells. T cell clonality was detected by PCR in all cases with increased cytotoxic T-cells in which adequate DNA was obtained from peripheral blood. Since in 2 patients the LDGL was not present at diagnosis but developed during follow up, our data suggests that clonal LDGL may develop in response to the HCL. The significance of LDGL in the setting of HCL and flow cytometric evaluation of HCL versus LDGL will be discussed.
Assuntos
Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/imunologia , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Feminino , Citometria de Fluxo , Rearranjo Gênico , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Only a few cases of primary gamma delta cutaneous T-cell lymphoma (CTCL) have been reported. We encountered 3 cases of this rare condition. OBJECTIVES: To characterize gamma delta CTCL by clinical, microscopic, and molecular methods and to investigate the role of Epstein-Barr virus (EBV) infection in its pathogenesis. DESIGN: Patients were evaluated by clinical examination, and biopsy specimens of lesional skin were examined by light microscopy and immunohistochemistry. Polymerase chain reaction amplification for T-cell receptor gamma gene rearrangements and in situ hybridization for EBV were performed on 3 biopsy specimens. SETTING: National Institutes of Health, a tertiary referral center. PATIENTS: Individuals with a clinical and histologic diagnosis of primary gamma delta CTCL. OUTCOME MEASURES: Clinical, light microscopic, and immunohistochemical features, and the presence of T-cell rearrangement and EBV RNA in biopsy specimens. RESULTS: Patients exhibited multiple plaques, tumors, and/or subcutaneous nodules primarily distributed over the extremities. Individuals exhibited an aggressive clinical course with resistance to multiagent chemotherapy and radiation. Microscopic examination revealed epidermotropism in 2 cases, a dermal infiltrate in all 3 cases, and subcutaneous involvement in 1 case. Immunohistochemical studies showed the presence of CD3(+)TCR delta(+) in 3 patients, CD8(+)in 1, and CD4(+), CD20(+), CD56(+), and beta F1(+) in none. All 3 cases exhibited an activated cytotoxic T-cell phenotype positive for T-cell intracellular antigen 1, perforin, and granzyme B. A clonal T-cell receptor gamma chain gene rearrangement was detected in all 3 cases by polymerase chain reaction. In situ hybridization was negative for EBV sequences in all 3 cases. CONCLUSION: gamma delta Cutaneous T-cell lymphomas are EBV-negative lymphomas that express a mature cytotoxic phenotype and have an aggressive clinical behavior. Arch Dermatol. 2000;136:1024-1032
Assuntos
Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Herpesvirus Humano 4/isolamento & purificação , Linfoma Cutâneo de Células T/virologia , RNA Viral/isolamento & purificação , Receptores de Antígenos de Linfócitos T gama-delta/genética , Neoplasias Cutâneas/virologia , Idoso , Tornozelo , Braço , Humanos , Imuno-Histoquímica , Hibridização In Situ , Linfoma Cutâneo de Células T/genética , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Assessing video imaging systems for measuring corneal topography often requires test surfaces. Steel bearings have been employed, but manufacturers caution that high reflectance (> 90%) relative to the eye (< 10%) may compromise test findings. The differences between steel and polycarbonate test surfaces are quantified in this study. METHODS: Images of a steel and a polycarbonate sphere of known radius of curvature were obtained with the Tomey/Computed Anatomy Topographic Modeling System (TMS, Cambridge, Mass). Analysis was performed on the raw video data files and the resultant surface curvature estimates. RESULTS: The raw video images differed sufficiently to affect image processing. Polycarbonate yielded consistently better images. Many steel images (approximately 25%) contained data points that could not be processed; calculated surface contour was more variable for these. Differences were less obvious when these images were removed from the pool. CONCLUSIONS: Results support the manufacturer's caution against the use of steel surfaces for testing or calibration of the TMS instrument. Problems appear due to the fundamental differences in the intensity distributions of video images captured from high- and low-reflectance surfaces.
Assuntos
Córnea/anatomia & histologia , Processamento de Imagem Assistida por Computador/métodos , Cimento de Policarboxilato , Aço , Calibragem , Humanos , Modelos AnatômicosRESUMO
The association of the Epstein-Barr virus with human immunodeficiency virus-associated primary central nervous system lymphomas is well known. We describe a pediatric patient infected with human immunodeficiency virus who developed a lesion in the central nervous system that appeared to be histologically reactive and that proved to be an Epstein-Barr virus-associated monoclonal B-cell lymphoproliferative disorder by molecular analysis. An 8-year-old girl was diagnosed with vertically transmitted human immunodeficiency virus infection at age 5, for which she was treated empirically with a combination of zidovudine and didanosine. At the age of 7 years, during evaluation for entry into an antiretroviral protocol, a single hypodense frontal lobe lesion was identified by computed tomography. After unsuccessful treatment for presumed toxoplasmosis and progressive neurologic deterioration, a stereotactic brain biopsy was performed. Although the biopsy contained a polymorphic lymphoid infiltrate that appeared to be cytologically reactive, polymerase chain reaction and in situ hybridization studies revealed a monoclonal Epstein-Barr virus-associated B-cell lymphoproliferative disorder, which was reminiscent of polymorphic B-cell hyperplasia observed in the setting of immunosuppression following organ transplantation. Postoperative therapy included steroids and antiretroviral therapy. The lesion decreased slightly in size, and the child's neurologic status was relatively unremarkable for 5 months. Subsequently, she developed cytomegalovirus retinitis, progressive encephalopathy, and died with pancytopenia. This case represents a newly described manifestation of Epstein-Barr virus-associated lymphoproliferative disorder, a diagnosis that should be considered in patients with neurologic symptoms and immunodeficiency. In addition, this case exhibited histologic features reminiscent of posttransplant lymphoproliferative disease, a histologic pattern that to our knowledge has not previously been reported in the setting of acquired immunodeficiency syndrome.
Assuntos
Complexo AIDS Demência/virologia , Encefalopatias/virologia , Infecções por Vírus Epstein-Barr/complicações , Linfoma Relacionado a AIDS/virologia , Transtornos Linfoproliferativos/virologia , Complexo AIDS Demência/diagnóstico , Anticorpos Monoclonais , Encefalopatias/diagnóstico , Criança , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/diagnóstico , Feminino , Humanos , Hiperplasia/diagnóstico , Imunofenotipagem , Hibridização In Situ , Linfoma Relacionado a AIDS/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Reação em Cadeia da PolimeraseRESUMO
The purpose of this study was to determine whether the visual acuity of keratoconic eyes was affected by alteration of back optic zone radii (BOZRs) of rigid gas permeable lenses (RGP) contact lenses. Visual acuity, spherical and sphero-cylindrical over-refraction and keratometry of the front surface of the RGP lenses of nine keratoconic eyes were measured. The BOZR of the five lenses varied from steeper to flatter than that habitually worn by the subjects. The steepest lenses produced significantly greater lens flexure and residual astigmatism (P < 0.002) and worse high and low contrast visual acuity with the spherical over-refraction (P < 0.05). There was no statistical difference in visual acuity across the range of BOZR when a sphero-cylindrical over-refraction was applied. Thus reduced visual acuity in keratoconus with steep lenses is likely due to uncorrected residual astigmatism from a combination of several possible sources.
RESUMO
PURPOSE: The purpose of this case report is to highlight the clinical characteristics of a recurrent chalazion through the use of digital photography and ultra-high resolution optical coherence tomography (UHROCT). CASE REPORT: A single case is presented, along with digital biomicroscopic photographs and UHROCT images. DISCUSSION: A review of the literature describing the histopathological and associations of chalazia and other disorders, suggest it may be possible to differentiate different eyelid conditions based on their clinical manifestations and appearance on UHROCT tomograms. Based on the images presented here, it appears that this case is typical of a post-menopausal incidence of chalazion and risk for acne rosacea.
Assuntos
Calázio/diagnóstico , Tomografia de Coerência Óptica , Calázio/tratamento farmacológico , Calázio/fisiopatologia , Lentes de Contato Hidrofílicas , Feminino , Humanos , Pessoa de Meia-Idade , RecidivaAssuntos
Herpesvirus Humano 8 , Neoplasias Intestinais/patologia , Neoplasias Intestinais/virologia , Linfoma Relacionado a AIDS/patologia , Linfoma Relacionado a AIDS/virologia , Adulto , Antígenos de Neoplasias/análise , Linfócitos B/imunologia , Humanos , Técnicas Imunoenzimáticas , Neoplasias Intestinais/imunologia , Linfoma Relacionado a AIDS/imunologia , Masculino , Linfócitos T/imunologiaAssuntos
Alcaloides/farmacologia , Microtúbulos/efeitos dos fármacos , Tubulina (Proteína)/metabolismo , Alcaloides/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Bovinos , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Células Cultivadas , Resistência a Medicamentos , Cinética , Microscopia Eletrônica , Paclitaxel , Relação Estrutura-AtividadeRESUMO
PURPOSE: To describe the refitting of a soft lens wearer into a silicone hydrogel lens due to neovascularization. This change, in turn, caused contact lens induced papillary conjunctivitis (CLPC) and a further refitting was necessary. METHODS: The patient was refit into a high Dk surface treated silicone hydrogel with a high modulus value. A second refitting was undertaken into a lower Dk silicone hydrogel contact lens with a lower modulus value which had no surface treatment but incorporated an internal wetting agent. RESULTS: A high Dk/t lens was used to resolve existing neovascularization and chronic hyperaemia. Subsequently, CLPC response occurred, possibly due to a combination of factors, resulting in irritation of the palpebral conjunctiva. This resulted in temporary lens discontinuation. A second silicone hydrogel lens was fit, along with the use of a non-preserved care system, which led to improvement and eventual resolution of the condition. CONCLUSION: High Dk silicone hydrogel lenses have shown excellent efficacy in resolving hypoxic complications such as neovascularization and hyperaemia. However, attention needs to be paid to their potential effect on the upper tarsal plate. More than one silicone hydrogel lens may be needed to help resolve these issues.