508 research outputs found

    Sexuality: A Queer Omission in U.S. Latino/a Theology

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    U.S. Latino/a theologies have been prophetically strident in calling out oppression of every sort for scrutiny — all, that is, except for sexuality: particularly homosexuality, around which they has been an embarrassing and stultifying silence. Nickoloff calls for a “teología homo de conjunto,” calling attention to questions of gender and sexuality, and the crossings between them, in contemporary critical theory and Latino/a theology

    Induction of the Synthesis of Triton-Soluble Proteins in Human Keratinocytes by Gamma Interferon

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    Recombinant human gamma interferon (r-IFN-γ) induces the synthesis and expression of HLA-DR antigen on cultured, normal, human keratinocytes depleted of Langerhans cells. After removal of r-IFN-γ from the culture medium of keratinocytes that are expressing HLA-DR antigen, the cells continue to express this antigen for at least 2 days. r-IFN-γ induces, in a dose dependent fashion, the synthesis of several triton-soluble proteins with the most prominent having an apparent molecular weight of 53,000. Whereas normal keratinocytes do not express HLADR antigen in vivo, they do express HLA-DR in a variety of skin diseases such as lichen planus, graft-versushost disease, and mycosis fungoides. We propose that an understanding of lymphocyte-keratinocyte interactions in vivo may be achieved by further studies of the mechanism of action of r-IFN-γ on cultured keratinocytes and that the results may provide insight into the pathophysiology leading to a number of common inflammatory and neoplastic skin diseases

    Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis

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    D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis

    AAPM/SNMMI Joint Task Force: report on the current state of nuclear medicine physics training

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    The American Association of Physicists in Medicine (AAPM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) recognized the need for a review of the current state of nuclear medicine physics training and the need to explore pathways for improving nuclear medicine physics training opportunities. For these reasons, the two organizations formed a joint AAPM/SNMMI Ad Hoc Task Force on Nuclear Medicine Physics Training. The mission of this task force was to assemble a representative group of stakeholders to:• Estimate the demand for board-certified nuclear medicine physicists in the next 5-10 years,• Identify the critical issues related to supplying an adequate number of physicists who have received the appropriate level of training in nuclear medicine physics, and• Identify approaches that may be considered to facilitate the training of nuclear medicine physicists.As a result, a task force was appointed and chaired by an active member of both organizations that included representation from the AAPM, SNMMI, the American Board of Radiology (ABR), the American Board of Science in Nuclear Medicine (ABSNM), and the Commission for the Accreditation of Medical Physics Educational Programs (CAMPEP). The Task Force first met at the AAPM Annual Meeting in Charlotte in July 2012 and has met regularly face-to-face, online, and by conference calls. This manuscript reports the findings of the Task Force, as well as recommendations to achieve the stated mission

    Childhood indicators of susceptibility to subsequent cervical cancer

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    Common warts could indicate cervical cancer susceptibility, as both are caused by human papillomavirus (HPV). Eczema was also investigated, as atopic eczema has been negatively associated with warts, but non-atopic eczema may be associated with compromised host defences, as observed in patients with HIV, suggesting increased susceptibility to HPV infection and cervical cancer. ‘Cervical cancer’ was self-reported during an interview by 87 of 7594 women members of two longitudinal British birth cohorts. The accuracy of the diagnoses is limited by lack of confirmation using medical records. Odds ratios are adjusted for common warts and eczema in childhood; and cigarette smoking, number of cohabiting partners and social class in early adult life. The odds ratios of warts and eczema with cervical cancer are 2.50 (95% confidence interval 1.14–5.47) and 3.27 (1.95–5.49), respectively. The association of eczema with cervical cancer is independent of hay fever as a marker of atopy, suggesting the importance of non-atopic eczema. Both heavier smoking compared with non-smoking and four or more cohabiting partners compared with one/none have odds ratios for cervical cancer of 8.26 (4.25–15.10) and 4.89 (1.39–17.18), respectively. Common warts in childhood may indicate cervical cancer susceptibility; this and the relationship with eczema deserves investigation

    Loss of miR-204 expression is a key event in melanoma

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    Cutaneous melanoma (CM) is a malignancy with increasing occurrence. Its microRNA repertoire has been defined in a number studies, leading to candidates for biological and clinical relevance: miR-200a/b/c, miR-203, miR-205, miR-204, miR-211, miR-23b and miR-26a/b. Our work was aimed to validate the role of these candidate miRNAs in melanoma, using additional patients cohorts and in vitro cultures. miR-26a, miR-204 and miR-211 were more expressed in normal melanocytes, while miR-23b, miR-200b/c, miR-203 and miR-205 in epidermis and keratinocytes. None of the keratinocyte-related miRNAs was associated with any known mutation or with clinical covariates in melanoma. On the other hand, the loss of miR-204 was enriched in melanomas with NRAS sole mutation (Fisher exact test, P = 0.001, Log Odds = 1.67), and less frequent than expected in those harbouring CDKN2A mutations (Fisher exact test, P = 0.001, Log Odds − 1.09). Additionally, miR-204 was associated with better prognosis in two independent melanoma cohorts and its exogenous expression led to growth impairment in melanoma cell lines. Thus, miR-204 represents a relevant mechanism in melanoma, with potential prognostic value and its loss seems to act in the CDKN2A pathway, in cooperation with NRAS

    The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation

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    Metnase is a human SET and transposase domain protein that methylates histone H3 and promotes DNA double-strand break repair. We now show that Metnase physically interacts and co-localizes with Topoisomerase IIα (Topo IIα), the key chromosome decatenating enzyme. Metnase promotes progression through decatenation and increases resistance to the Topo IIα inhibitors ICRF-193 and VP-16. Purified Metnase greatly enhanced Topo IIα decatenation of kinetoplast DNA to relaxed circular forms. Nuclear extracts containing Metnase decatenated kDNA more rapidly than those without Metnase, and neutralizing anti-sera against Metnase reversed that enhancement of decatenation. Metnase automethylates at K485, and the presence of a methyl donor blocked the enhancement of Topo IIα decatenation by Metnase, implying an internal regulatory inhibition. Thus, Metnase enhances Topo IIα decatenation, and this activity is repressed by automethylation. These results suggest that cancer cells could subvert Metnase to mediate clinically relevant resistance to Topo IIα inhibitors

    Expression of the chemokine receptor CCR5 in psoriasis and results of a randomized placebo controlled trial with a CCR5 inhibitor

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    Several reports have indicated that the chemokine receptor CCR5 and its ligands, especially CCL5 (formerly known as RANTES), may play a role in the pathogenesis of psoriasis. The purpose of this investigation was to examine the expression of CCR5 and its ligands in chronic plaque psoriasis and to evaluate the clinical and immunohistochemical effect of a CCR5 receptor inhibitor. Immunohistochemical analysis showed low but significant increased total numbers of CCR5 positive cells in epidermis and dermis of lesional skin in comparison to non-lesional skin. However, relative expression of CCR5 proportional to the cells observed revealed that the difference between lesional and non-lesional skin was only statistically significant in the epidermis for CD3 positive cells and in the dermis for CD68 positive cells. Quantification of mRNA by reverse transcriptase-polymerase chain reaction only showed an increased expression of CCL5 (RANTES) in lesional skin. A randomized placebo-controlled clinical trial in 32 psoriasis patients revealed no significant clinical effect and no changes at the immunohistochemical level comparing patients treated with placebo or a CCR5 inhibitor SCH351125. We conclude that although CCR5 expression is increased in psoriatic lesions, this receptor does not play a crucial role in the pathogenesis of psoriasis
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