A comprehensive framework for evaluating the environmental health and safety implications of engineered nanomaterials

Engineered nanomaterials (ENM) are a growing aspect of the global economy, and their safe and sustainable development, use, and eventual disposal requires the capability to forecast and avoid potential problems. This review provides a framework to evaluate the health and safety implications of ENM releases into the environment, including purposeful releases such as for antimicrobial sprays or nano-enabled pesticides, and inadvertent releases as a consequence of other intended applications. Considerations encompass product life cycles, environmental media, exposed populations, and possible adverse outcomes. This framework is presented as a series of compartmental flow diagrams that serve as a basis to help derive future quantitative predictive models, guide research, and support development of tools for making risk-based decisions. After use, ENM are not expected to remain in their original form due to reactivity and/or propensity for hetero-agglomeration in environmental media. Therefore, emphasis is placed on characterizing ENM as they occur in environmental or biological matrices. In addition, predicting the activity of ENM in the environment is difficult due to the multiple dynamic interactions between the physical/chemical aspects of ENM and similarly complex environmental conditions. Others have proposed the use of simple predictive functional assays as an intermediate step to address the challenge of using physical/chemical properties to predict environmental fate and behavior of ENM. The nodes and interactions of the framework presented here reflect phase transitions that could be targets for development of such assays to estimate kinetic reaction rates and simplify model predictions. Application, refinement, and demonstration of this framework, along with an associated knowledgebase that includes targeted functional assay data, will allow better de novo predictions of potential exposures and adverse outcomes.     

Brk is coamplified with ErbB2 to promote proliferation in breast cancer

Amplification of the receptor tyrosine kinase ErbB2 is frequently observed in breast cancer. Amplification of erbB2 is also associated with multiple genomic gains and losses; however, the importance of these associated changes is largely unknown. We demonstrate that Brk, a cytoplasmic tyrosine kinase, is coamplified and coexpressed with ErbB2 in human breast cancers. ErbB2 interacts with Brk and increases its intrinsic kinase activity. Expression of Brk enhances the ErbB2-induced activation of Ras/MAPK signaling and cyclin E/cdk2 activity to induce cell proliferation of mammary 3-dimensional acini in culture. In a murine model of breast cancer, expression of Brk was found to shorten the latency of ErbB2-induced tumors by promoting cell proliferation, with no effect on protection from apoptosis. Furthermore, overexpression of Brk conferred resistance to the ability of Lapatinib, an ErbB2 kinase inhibitor, to inhibit ErbB2-induced proliferation. Thus, we identified Brk as a drug target for ErbB2-positive cancers.     

Childhood acute myeloblastic leukemias. Report of 21 cases

Between 1989 and 1996, 21 cases with acute non lymphoblastic leukemia (11 males and 10 females) were diagnosed in our institution. Median age was 9 years (range, 2-15 years). Leukocyte count was more than 50,109/l in 47% of cases. According to the French-American-British (FAB) criteria, 7 cases were classified M1, 10 cases were classified M2, 1 classified M4Eo and 3 classified M5. All patients were treated with "7 + 3" protocol and complete remission was achieved in 17 cases (80%), 2 cases (10%) failed to respond and 2 (10%) died during induction. Relapse was observed in 15 cases. The 3-year survival rate was 20% and the relapse-free-survival rate was 12% confirming the worse prognosis of this leukemia when treated with standard chemotherapy.     

Do prothrombin time, transaminases, and platelet count predict the severity of fibrosis in viral liver diseases?

The goal of our study is to assess the performance of a score combining 3 serological parameters (PT, platelets and transminases) in predictive hepatic fibrosis. The study involved 54 patients, 29 of which resulted in distributing them according to the score of Metavir into 2 groupes: Group A with mild fibrosis (F1,F2) and group B with severe fibrosis (F3,F4). PT, platelets and transminase values in serum were assessed for all patients. The total score of the 3 biological parameters combined, was significantly more elabled in the severe fibrosis group than in the mild fibrosis group (P = 0.01) but it was not of much importance in 30% of cases as it did not allow to classify the patients with certainty in group A or in group B. This score does not seem to grant exemption from needle liver biopsy, but it can be improved by the association of other direct markers of fibrosis.     

Orbital location of Kaposi's sarcoma

Kaposi's sarcoma is a proliferative disease, probably induced by human herpes virus type 8 (HHV8). Its expression is cutaneous and visceral, with four clinical forms. An orbital location of Kaposi's sarcoma remains exceptional. In order to evaluate the epidemiological, clinical, and therapeutic objectives of this tumor location, we report a case of a 58-year-old patient hospitalized in the ophthalmology department for a surgically treated right orbital tumor.