Chemotherapeutic Agents in Noncytotoxic Concentrations Increase Antigen Presentation by Dendritic Cells via an IL-12-Dependent Mechanism

Antineoplastic chemotherapeutic agents may indirectly activate dendritic cells (DCs) by inducing the release of danger signals from dying tumor cells. Whereas the direct cytotoxic or inhibitory effect of conventional chemotherapy on DCs has been reported, modulation of DC function by chemotherapeutic agents in low noncytotoxic concentrations has not yet been investigated. We have tested the effects of different classes of antineoplastic chemotherapeutic agents used in low noncytotoxic concentrations on the Ag-presenting function of DCs. We revealed that paclitaxel, doxorubicin, mitomycin C, and methotrexate up-regulated the ability of DCs to present Ags to Ag-specific T cells. Stimulation of DC function was associated with the up-regulation of expression of Ag-processing machinery components and costimulatory molecules on DCs, as well as increased IL-12p70 expression. However, the ability of DCs treated with paclitaxel, methotrexate, doxorubicin, and vinblastine to increase Ag presentation to Ag-specific T cells was abolished in DCs generated from IL-12 knockout mice, indicating that up-regulation of Ag presentation by DCs is IL-12-dependent and mediated by the autocrine or paracrine mechanisms. At the same time, IL-12 knockout and wild-type DCs demonstrated similar capacity to up-regulate OVA presentation after their pretreatment with low concentrations of mitomycin C and vincristine, suggesting that these agents do not utilize IL-12-mediated pathways in DCs for stimulating Ag presentation. These findings reveal a new mechanism of immunopotentiating activity of chemotherapeutic agents-a direct immunostimulatory effect on DCs (chemomodulation)-and thus provide a strong rationale for further assessment of low-dose chemotherapy given with DC vaccines for cancer treatment. The Journal of Immunology, 2009, 183: 137-144.

Distinct localization of T cell Agrin during antigen presentation - evidence for the expression of Agrin receptor(s) in antigen-presenting cells

Agrin is over-expressed by activated and autoimmune T cells, and synergizes with the T cell receptor (TCR) to augment cell activation. In the present study, we show that Agrin accumulates to distinct areas of the plasma membrane and that cell activation causes its redistribution. During antigen presentation, Agrin primarily accumulates to the periphery of the mature immunological synapse, mostly in lamellipodia-like protrusions that wrap around the antigen-presenting cell and, conversely, anti-Agrin sera induced a significant redistribution of TCR at the plasma membrane. We also provide evidence for the expression of Agrin receptors in peripheral blood monocytes, dendritic cells and a fraction of B cells. Interestingly, interferon-a treatment, which induces the expression of Agrin in T cells, also augmented Agrin binding to monocytes. Stimulation of monocytes with recombinant Agrin induced the clustering of surface receptors, including major histocompatibility complex class II, activation of intracellular signalling cascades, as well as enhanced dsRNA-induced expression of pro-inflammatory cytokines interleukin-6 and tumour necrosis factor-a. Collectively, these results confirm the location of Agrin at the immunological synapse between T cells and antigen-presenting cells and justify further characterization of its receptors in the immune system.

Anestesia e o usuário de Ecstasy

JUSTIFICATIVA E OBJETIVOS: Nos últimos anos o número de novos usuários de agentes ilícitos tem aumentado de forma significativa em todo o mundo. A maconha e a cocaína, além do álcool e do tabaco, têm sido os agentes citados com freqüência, porém houve um aumento significativo de usuários de outros agentes psicoestimulantes ou alucinógenos, como o Ecstasy, o GHB, o LSD e a metanfetamina, empregados com o objetivo de intensificar as experiências sociais. O objetivo do presente artigo foi discutir a apresentação clínica, os efeitos deletérios e as potenciais interações com o ato anestésico no paciente cirúrgico usuário desses agentes ilícitos. CONTEÚDO: O artigo discute os mecanismos de ação, a apresentação clínica, os efeitos deletérios e as possíveis repercussões observadas durante a anestesia no usuário de MDMA (3,4-metilenodioximetanfetamina), também conhecido como Ecstasy. CONCLUSÕES: A apresentação clínica e os efeitos deletérios provocados pelo 3,4-metilenodioximetanfetamina (Ecstasy), assim como potenciais interações com o ato anestésico devem ser do conhecimento do anestesiologista, pois em muitas situações esses usuários serão submetidos a intervenções cirúrgicas de emergência, ou mesmo eletivas.

Criteria for the diagnosis of diffuse uterine myohypertrophy

Objectives: Diffuse uterine myohypertrophy (DUMH) is a condition clinically diagnosed by the presence of uterine bleeding, homogeneous and diffuse uterine enlargement, and absence of any myoendometrial cause of bleeding. Since the morphologic criteria for the diagnosis of this entity are still controversial, this study aimed to investigate the clinical presentation and the morphologic findings of the cases of DUMH presenting at the University Hospital of Botucatu, São Paulo, Brazil, Methods: We retrospectively studied 43 consecutive patients with DUMH submitted to hysterectomy (test group) and compared the findings with those obtained from 28 patients submitted to hysterectomy due to a prolapsed uterus (control group). There were no significant differences in age, weight or height between the two groups. Results: the uterine weight of the DUMH group (mean +/- S.D. 157.4 +/- 46.4 g) was significantly heavier than that of the control group (99.5 +/- 35.4 g) and myometrial thickness was significantly greater in the DUMH group (2.5 +/- 0.5 cm) than in the control group (1.9 +/- 0.4 cm). No positive correlation was observed between increased uterine weight and parity, but there was a positive correlation between uterine weight and myometrial thickness. on the basis of the present study, we suggest that the diagnosis of DUMH be made clinically and in cases of uterine weight greater than or equal to 120 g and myometrial thickness greater than or equal to 2.0 cm. In addition, 10 cases of each group were analyzed by morphometry to evaluate interstitial fibrosis and myometrial hypertrophy. The data showed that the increase in uterine weight in DUMH is caused by enlargement of individual myometrial fibers rather than accumulation of interstitial collagen. Conclusion: Discriminant analysis to estimate the diagnostic significance of a number of clinical and pathologic variables (age, parity, uterine weight and morphometric parameters) was able to differentiate cases of DUMH from controls in 100% of the patients.

Management of an Unusual Presentation of Ascher Syndrome

Ascher syndrome is defined by the association between double lip, blepharochalasis, and nontoxic goiter. Because it is a rare disease, it is most often misdiagnosed, despite its implications for quality of life. We report a variation of an incomplete type of Ascher syndrome affecting the upper lip, upper eyelids, and lateral canthi of a young male patient. The surgical management, follow-up, and a brief overview of the syndrome are described. The results presented show an aesthetic and functional improvement of the facial deformities.

Latin America and the Caribbean: policies to improve linkages with the global economy

Includes bibliography

Summary of the presentation at the seminar on the regulation of public utilities: water and electricity

Includes bibliography

Summary of the presentation at the seminar on the regulation of public utilities: water and electricity

Includes bibliography

Sumary of the presentation at the seminar on the regulation of public services: water and elctricity

Includes bibliography

Post-ganglionic Horner's syndrome: An unusual presentation of non-Hodgkin lymphoma

In this paper, we present the rare case of a patient with cervical lymphadenopathy diagnosed as a T-cell-rich B-cell non-Hodgkin lymphoma that manifested Horner's syndrome due to a post-ganglionic sympathetic neuron lesion caused by the tumor. Copyright © 2012 S. Karger AG, Basel.

Unusual presentation of oral squamous cell carcinoma in a young woman

Oral squamous cell carcinoma (OSCC) is the most common oral malignant neoplasm, mainly affecting individuals over 50 years old with a history of tobacco and alcohol use. The occurrence of this oral cancer in individuals under 40 years old is unusual and, when it does occur, shows a weaker relation to those risk factors and a more aggressive clinical course. Due to the paucity of reports in this population, it is difficult to prove its increasing trend. A case of oral squamous cell carcinoma in a 39-year-old woman with no history of tobacco or alcohol use is reported. Clinical and histopathological findings, aetiology, and treatment are discussed. The increasing trend of oral squamous cell carcinoma in young women without known risk factors highlights the need for clinicians to be prepared to diagnose this lesion quickly and precisely, providing a better prognosis, chance of survival, and quality of life for the patient.

Scope, objectives and special problems of planning for agricultural development with reference to Barbados

Describe la organización, metas y objetivos del proceso de planificación para el desarrollo de la agricultura en Barbados.