Mad2 overexpression promotes aneuploidy and tumorigenesis in mice

Mad2 is an essential component of the spindle checkpoint that blocks activation of Separase and dissolution of sister chromatids until microtubule attachment to kinetochores is complete. We show here that overexpression of Mad2 in transgenic mice leads to a wide variety of neoplasias, appearance of broken chromosomes, anaphase bridges, and whole-chromosome gains and losses, as well as acceleration of myc-induced lymphomagenesis. Moreover, continued overexpression of Mad2 is not required for tumor maintenance, unlike the majority of oncogenes studied to date. These results demonstrate that transient Mad2 overexpression and chromosome instability can be an important stimulus in the initiation and progression of different cancer subtypes

Case of relapsed AIDS-related plasmablastic lymphoma treated with autologous stem cell transplantation and highly active antiretroviral therapy

Plasmablastic lymphoma is a rare and aggressive malignancy strongly associated with HIV infection. The refractory/relapsed disease rate is high, and the survival rate is characteristically poor. There are no satisfactory salvage regimens for relapsed cases. We successfully performed autologous stem cell transplantation using a regimen consisting of MCNU (ranimustine), etoposide, cytarabine, and melphalan in a Japanese patient with relapsed AIDS-related plasmablastic lymphoma of the oral cavity. Highly active antiretroviral therapy continued during the therapy. Therapy-related toxicity was tolerable, and a total of 40 Gy of irradiation was administered after autologous stem cell transplantation. The patient has remained in complete remission for 16 months since transplantation

Phlebotomine fauna (Diptera: Psychodidae) of an American cutaneous leishmaniasis endemic area in the state of Mato Grosso do Sul, Brazil

The occurrence of an outbreak of cutaneous leishmaniasis associated with Leishmania (Leishmania) amazonensis in the municipality of Bela Vista, state of Mato Grosso do Sul, Brazil, and the absence of information on its vectors in this area led the authors to undertake captures of phlebotomine sand flies, using Shannon traps and automatic CDC light traps, in domiciles, forested areas and animal shelters from February 2004-January 2006. A total of 808 specimens belonging to 18 sandfly species have been identified: Bichromomyia flaviscutellata,Brumptomyia avellari, Brumptomyia brumpti, Brumptomyia sp, Evandromyia aldafalcaoae, Evandromyia cortelezzii, Evandromyia evandroi, Evandromyia lenti, Evandromyia teratodes, Evandromyia termitophila, Lutzomyia longipalpis, Nyssomyia whitmani, Pintomyia christenseni, Psathyromyia aragaoi, Psathyromyia campograndensis, Psathyromyia punctigeniculata, Psathyromyia shannoni and Sciopemyia sordellii. The presence of Lu. longipalpis, Ny. whitmani and Bi. flaviscutellata, vectors of Leishmania chagasi, Leishmania braziliensis and L. amazonensis, respectively, has increased.FUNDECT - DECIT Departamento de Ciência e Tecnologia do Ministério da Saúd

Ubiquitination regulates PTEN nuclear import and tumor suppression

The PTEN tumor suppressor is frequently affected in cancer cells, and inherited PTEN mutation causes cancer-susceptibility conditions such as Cowden syndrome. PTEN acts as a plasma-membrane lipid-phosphatase antagonizing the phosphoinositide 3-kinase/AKT cell survival pathway. However, PTEN is also found in cell nuclei, but mechanism, function, and relevance of nuclear localization remain unclear. We show that nuclear PTEN is essential for tumor suppression and that PTEN nuclear import is mediated by its monoubiquitination. A lysine mutant of PTEN, K289E associated with Cowden syndrome, retains catalytic activity but fails to accumulate in nuclei of patient tissue due to an import defect. We identify this and another lysine residue as major monoubiquitination sites essential for PTEN import. While nuclear PTEN is stable, polyubiquitination leads to its degradation in the cytoplasm. Thus, we identify cancer-associated mutations of PTEN that target its posttranslational modification and demonstrate how a discrete molecular mechanism dictates tumor progression by differentiating between degradation and protection of PTEN

East London’s Homeless: a retrospective review of an eye clinic for homeless people

Background There is very little published work on the visual needs of homeless people. This paper is the first study to investigate the visual needs of homeless people in the UK. Although similar work has been done in other countries, this study is unique because the United Kingdom is the only country with a National Health Service which provides free healthcare at the point of access. This study analysed the refractive status of the sample used, determined the demographics of homeless people seeking eye care and established if there is a need for community eye health with access to free spectacle correction in East London. Methods This retrospective case study analysed the clinical records of 1,141 homeless people using the Vision Care for Homeless People services at one of their clinics in East London. All eye examinations were carried out by qualified optometrists and, where appropriate, spectacles were dispensed to patients. Data captured included age, gender, ethnicity and refractive error. Results were analysed using two-sample t-tests with Excel and Minitab. Results Demographics of age, gender and ethnicity are described. Spherical equivalents (SE) were calculated from prescription data available for 841 clinic users. Emmetropia was defined as SE–0.50DS to +1DS, myopia as SE  +1DS. The majority of clinic users were male (79.2 %, n = 923). Approximately 80 % (n = 583) of clinic users were white, 10 % (n = 72) were ‘black’, 4 % (n = 29) ‘Asian’ and the remaining 5.6 % (n = 40) were of ‘mixed ethnicity’ and ‘other’ groups. The mean age of females attending the clinic was significantly lower than that of males (45.9 years, SD = 13.8 vs’ 48.4 years, SD = 11.8) when analysed using a two-sample t-test (t (317) = 2.44, p = 0.02). One third of service users were aged between 50–59 years. Myopia and hyperopia prevalence rates were 37.0 % and 21.0 % respectively. A total of 34.8 % of homeless people were found to have uncorrected refractive error, and required spectacle correction. Conclusions This study has identified a high proportion of uncorrected refractive error in this sample and therefore a need for regular eye examinations and provision of refractive correction for homeless people