1,354,933 research outputs found

    Productive HIV-1 infection of normal human mammary epithelial cells

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    Objective and design: To determine the susceptibility of mammary epithelial cells (MEG) to HIV-1 as breastfeeding is an established route of HIV transmission, although the origin of virus in breastmilk is unclear. Methods: Primary epithelial cell cultures were derived from the mammary glands of healthy donors; immortalized MEC lines were also used. HIV infection was followed by detection of infectious particle production, p24 antigen and viral sequences. Results: Seven out of 11 primary MEC cultures and two out of three MEC lines were productively infected by HIV-1. Virus replication significantly reduced cell proliferation, although cell viability was only slightly affected. Cytopathic changes were not observed. MEC cultures expressed low levels of surface CD4, galactosylceramide and CD26, but essentially no human leukocyte antigen (HLA)-DR. Infection of HIV-permissive MEC cells was associated with the upregulation of surface HLA-DR and CD26. In contrast, the expression of CD4, tissue-specific markers, adhesion molecules and growth-factor receptors was downregulated. To a lesser extent, similar effects were also observed in non-permissive cells. Hormones (triiodothyronine plus beta-estradiol and prolactin) enhanced HIV replication, possibly through the stimulation of cellular DNA synthesis. Conclusions: We concluded that HIV-1 replication in ductal/alveolar MEC may be, in part, responsible for the presence of HIV-1 in milk; that hormones may stimulate virus replication; and that infection reduces the growth of epithelial cells. Although in vitro HIV is produced by MEC to a lesser extent than lymphoid cells, MEG-derived HIV might have selective advantages for the infection of mucosal epithelial cells during breastfeeding

    Palladium-catalyzed intramolecular arylation of electron-poor heterocycles

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    Formation of aryl-aryl bonds is a very interesting reaction especially for the synthesis of new chemical entities in drug discovery[1]. One of the most utilized method is the metal-catalyzed cross-coupling reaction with the limitation of the use of activating group in both of the arene coupling partner. Recently palladium-catalyzed direct arylations have emerged as attracting alternative. The advantage of this reaction consist in the opportunity to start from very simple building blocks: a non-activated aryl C-H bond and an aryl-halide. Most literature citation involves electron rich substrate[2], on the contrary there are only few examples regarding electron-poor heterocycles[3]; we report intramolecular version of this reaction regarding azines and diazines. Starting from functionalized nicotinic amides and 1,2-, 1,3- and 1,4-diazine amides, in only one step, azapolycyclic systems are obtaine

    Fred Basolo and the (Re)naissance of American Inorganic Chemistry

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    It was an Australian/British chemist, Sir Ronald Nyholm, who first spoke of a “renaissance” of inorganic chemistry; but its emergence as a newly dynamic subfield, beginning in the 1950s, can be seen even more clearly in the US. While John Bailar is often credited as the “Father of American Inorganic Chemistry,” it is arguable that Fred Basolo, Bailar’s student at Illinois, has had the most lasting impact on the dramatic growth of the field in American academia. Justification for that assertion includes the remarkable representation of his academic descendants among inorganic faculty members of American universities; comments and reminiscences from the students he trained; and an examination of his seminal contributions in the form of both original research and textbooks, particularly the groundbreaking 1958 work Mechanisms of Inorganic Reactions, written with his Northwestern colleague Ralph Pearson, which played a central role in raising the intellectual stature of inorganic chemistry by bringing the study of mechanism to the forefront

    Growth-stimulating activity of interleukin 6 on human mammary epithelial cellstransfected with the int-2 gene

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    We have shown recently that normal human mammary epithelial cells do produce interleukin 6 (IL6), interleukin 8, and a nonsecreted form of tumor necrosis factor. Here we report that ductal infiltrating mammary carcinomas fail to express immunoreactive IL6. Since abnormalities of cytokine genes are a frequent event in cancer, we investigated the production of and the response to cytokines of mammary cells using a panel of oncogene-transformed cells derived from the spontaneously immortalized MCF-10A cell line. We found that only the parental line and the int-2-transformed cells responded to exogenous 1L6 and/or were suppressed by IL6-neutralizing antibody. In contrast to highly transformed cells, these two lines, which were either nontransformed (MCF-10A) or weakly transformed (int-2), were found to express IL6 receptors. These data suggest that loss of IL6 pathways can be a marker of mammary cell transformation

    Thomas Basolo (MSW) Social Work

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    This episode of Confluence is the second in a two-part series honoring our graduate student veterans during Veterans Week. Thomas Basolo retired from the military in 2017. In this episode, we discuss his study in social work, his service ethic, and his support for other veterans who are struggling with a variety of issues as they acclimate to civilian life, especially addiction. On Confluence, we are proud to celebrate these veterans who bring their commitment to service, their discipline, and their support of their fellow human beings to their work as graduate students. The world is a better place when our veterans get the support they need to grow and develop when their service to our nation’s military is done. We are delighted to share their stories with our listeners.https://scholarworks.umt.edu/confluence_podcast/1074/thumbnail.jp

    MATRIGEL PROMOTES RETINOBLASTOMA CELL-GROWTH INVITRO AND INVIVO

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    Cells derived from retinoblastomas grow slowly in vitro and only very rarely form tumors in nude mice. Matrigel, a mixture of components normally found in basement membranes, promotes the growth of Y-79 and WERI-RbI retinoblastoma (Rb) cells when added to suspension cultures of the 2 Rb cell lines. It also substantially increases cell adhesion in vitro. Y-79 cells, seeded into a Matrigel matrix, form round colonies over a 3-week period similar to those of control, weakly metastatic murine melanoma cells. In vivo, s.c. co-injection of Matrigel with either Y-79 or WERI-RbI cells into nude mice promotes retinoblastoma tumor formation. Transplantation of as few as 1,000 cells allows for xenografting under these conditions, while no tumors were observed in the absence of Matrigel, even at 10 x 10(6) cells/inoculum. The tumors produced have the expected morphology and express an mRNA for a highly specific retina/retinoblastoma marker protein, the interphotoreceptor retinoid-binding protein. Thus, the xenografts obtained maintain the original morphological and molecular characteristics of the injected cells and represent a useful model for in vivo studies of retinoblastoma growth and treatment

    Mechanistic turn in inorganic textbooks: Basolo and Pearson's Mechanisms of Inorganic Reactions

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    Widespread interest in mechanistic work among Inorg. chemists did not really appear until the 1950s, considerably later than for their org. colleagues. Ronald Nyholm and others have identified a mid-century "renaissance" of inorg. chem., and the turn towards mechanism played a major part in that development. I will discuss the central role of Fred Basolo and Ralph Pearson's 1958 monograph "Mechanisms of Inorg. Reactions" in influencing that turn, based upon a combined horizontal and vertical sampling of inorg. textbooks around that period

    NanoString in the screening of genetic abnormalities associated with thyroid cancer

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    In the setting of cancer pathology, molecular characterization of tumors providing diagnostic and predictive information is acquiring more and more relevance. Moreover, the advent of innovative technologies continuously improves the knowledge of the molecular landscape of tumors and strengthens the links between clinics, tumor pathology and molecular features. In the clinical management of patients with thyroid nodules and thyroid tumors, the aid of molecular testing is encouraged but still not strongly recommended by current guidelines. Also for this reason this field of study is attracting much interest. The nCounter system is a relatively new technology based on a direct hybridization of fluorescent probes to specific nucleic acid targets, followed by digital measurement of signals; the reaction is highly multiplexable and results are robust and reproducible. This review reports and discusses the available data related to the application of this specific technique to thyroid nodules and thyroid tumors samples. The available data indicate that nCounter system represents a solid approach for the research of relevant diagnostic and prognostic biomarkers in thyroid pathology

    Molecular genetics of follicular-derived thyroid cancer

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    Thyroid cancer is the most common type of endocrine-related malignancy, whose incidence rates have increased dramatically in the last few decades. Neoplasms of follicular origin generally have excellent prognosis, with the exception of less differentiated tumors. Follicular-derived thyroid cancer can manifest as a variety of morphologically distinct entities, characterized by various degrees of differentiation and invasiveness. Histological evaluation is thus crucial for the definition of patients’ prognosis. However, within each histological subtype, tumor behavior can be highly variable, and, in this respect, molecular characterization can provide insightful information to refine the risk stratification of tumors. In addition to the importance of its prognostic role, molecular testing can be used to support the differential diagnosis of thyroid nodules in the absence of marked cyto-morphological aberrations. Finally, with the advent of targeted drugs, the presence of molecular alterations will guide the therapeutic strategies for patients with advanced tumors who do not respond to standard treatment. This review aims to describe the genetic landscape of follicular-derived thyroid tumors also highlighting differences across histological subtypes

    Sudden death in a case of recurrent Takotsubo syndrome

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    Herein we report an unusual case of sudden death occurring in a 65 year old woman during a minor oral surgery. The subject, who had a medically treated anxiety, had a history of two reversible left ventricle dysfunction episodes consistent with recurrent Takotsubo Syndrome that had occurred seven and six years before, respectively. She also suffered from moderate, well treated post-menopausal systemic hypertension. Post-mortem examination showed apical biventricular ballooning of the heart with no cardiac rupture, coronary artery lesion or other cardiac/extra-cardiac disease. Toxicological tests and forensic investigations excluded unnatural causes of death, including pharmacological or iatrogenic causes related to medical malpractice. Only non-specific contraction bands and mild hypertrophy were observed by histology in the left ventricle myocytes. Takotsubo syndrome is usually an acute and reversible heart failure syndrome with acute left ventricle apex ballooning, no coronary artery disease or other macroscopic or microscopic cardiac changes; physical or emotional stress are well known triggering factors. Nevertheless, recurrent forms, major cardiac adverse events and even sudden death may occur in a minority of cases, meaning that a diagnosis of Takotsubo syndrome must be considered in cases of sudden death and in forensic investigations
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