A Bio-Conjugated Fullerene as a Subcellular-Targeted and Multifaceted Phototheranostic Agent

Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C₇₀@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C₇₀@lysozyme are confirmed using UV-visible and 2D ¹H, ¹⁵N NMR spectroscopy. The excellent imaging contrast of C₇₀@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C₇₀@lysozyme and its ability to initiate cell death by means of singlet oxygen (¹O₂) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C₇₀@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.     

Modeling and sensitivity analysis of fire emissions in southern Africa during SAFARI 2000

This paper uses three recently generated southern African satellite burned area products for the month of September 2000 in a sensitivity study of regional biomass burning emissions for a number of trace gases and particulates. Differences in the extent and location of areas burned among products generated from Moderate Resolution Imaging Spectroradiometer (MODIS), Systeme Pour l'Observation de la Terre (SPOT-VEGETATION), and Along Track Scanning Radiometer (ATSR-2) data are significant and result in different emissions estimates for woodland and grassland land cover types. Due to the different emission profiles in woodlands and grasslands, favoring relatively more products of incomplete combustion in woodlands compared with products of complete combustion in grasslands in the late dry season, these changes are not proportional to the differences in the burned area amounts. The importance of accurate burned area information not just in terms of the total area but also in terms of its spatial distribution becomes apparent from our modeling results. This paper highlights the urgent need for satellite data producers to provide accuracy assessments associated with satellite-derived products. Preferably, these accuracy data will be spatially explicit, or defined in a way that can be applied in a spatially explicit modeling context, to enable emissions uncertainties to be defined with respect to different landscape units in support of greenhouse gas emissions reporting.     

The "Nobel": Prize and swindle. The betrayed testament

Human glutathione S-transferase pi (GST-pi) may serve as a useful tumor marker because of the high frequency with which it is found in elevated levels in several tumor types. To determine whether GST-pi is useful as an indicator for cancers of the head and neck, expression of GST-pi mRNA was investigated by Northern analysis in this tumor type. Overexpression of GST-pi mRNA was detected in 9 of 36 (25%) primary head and neck squamous cell carcinomas (HNSCCs). When Southern blot analysis was used to examine the relationship between overexpression and amplification of the GST-pi gene, only 3 of 36 tumors (8%) showed GST-pi gene amplification. Thus, gene amplification is not critical to GST-pi mRNA overexpression in HNSCCs. Moderately and poorly differentiated HNSCCs tended to manifest elevated GST-pi mRNA compared with well differentiated tumors (30% for moderately and poorly differentiated tumors versus none of the well differentiated tumors examined). However, there was no significant correlation between GST-% mRNA overexpression and clinical stage, T stage (tumor size), N stage (neck nodal status), pathological nodes, or patient survival.     

Common region of ALL-1 gene disrupted in epipodophyllotoxin-related secondary acute myeloid leukemia

Translocations at chromosomal band 11q23 characterize most de novo acute lymphoblastic leukemias (ALL) of infants, acute myeloid leukemias (AML) of infants and young children, and secondary AMLs following epipodophyllotoxin exposure. The chromosomal breakpoints at 11q23 have been cloned from isolated cases of de novo ALL and AML. Using an 859-base pair BamHI fragment of human ALL-1 complementary DNA that recognizes the genomic breakpoint region for de novo ALL and AML, we investigated two cases of secondary AML that followed etoposide-treated primary B-lineage ALL. In the first case, the translocation occurred between chromosomes 9 and 11 and the breakpoint at 11q23 localized to the same 9-kilobase region of the ALL-1 gene that is disrupted in most of the de novo leukemias. In the second case the translocation was between chromosomes 11 and 19. The breakpoint occurred outside of the ALL-1 breakpoint cluster region.     

The murine Tcl1 oncogene: embryonic and lymphoid cell expression

In human leukemias and lymphomas nonrandom chromosomal rearrangements cause changes in cell growth and/or survival in such a way as to promote malignancy. The detailed study of the biochemical and genetic pathways altered in human cancer requires the identification or development of models to allow the study and manipulation of cancer gene function. Recently, the breakpoint gene TCL1, involved in chromosome translocations observed mostly in mature T-cell proliferations and chronic lymphocytic leukemias (CLL), was isolated and characterized, and showed to be part of a new gene family of proteins involved in these tumors. The murine Tcl1 gene, is similar in sequence to the murine and human MTCP1 gene also involved in T cell leukemias. The murine Tcl1 gene was shown to reside on mouse chromosome 12 in a region syntenic to human chromosome 14. Furthermore, we show that the murine Tcl1 gene is expressed early in mouse embryonic development and demonstrates expression in fetal hematopoietic organs as well as in immature T and B cells. Characterization of the murine Tcl1 gene will help in developing a mouse model of CLL and would provide the best opportunity to study and decipher the role of TCL1 in malignant transformation.     

Gamma-Ray-Induced Multi-Effect on Properties of Chalcogenide Glasses

Gamma-ray irradiations induced various alterations in sulfur- and selenium-based chalcogenide glasses. The absorbed dose was in the range of 0.01–3.6 MGy. The glasses exhibit prominent sensitivity to γ-ray irradiation, characterized by changes in some of the physical properties of the glasses, e.g., optical transmission, optical band gap, density, and thermal expansion coefficient. The effects on glass structure and microscopic morphology were also studied by Raman spectra and scanning electron microscopic observations.     

Value of early variables as predictors of short-term outcome in patients with acute focal cerebral ischemia

The pathogenesis of essential thrombocythemia as a clonal myeloproliferative disorder has been clearly established. However, there continues to be considerable controversy concerning the management of this disease, particularly because its natural history is consistent with a nearly normal life expectancy. Therapeutic decisions have been complicated by a reliance on largely anecdotal, retrospective experience in the medical literature and, until very recently, an absence of prospective, controlled clinical trials. A recent study of patients with essential thrombocythemia at high risk of thrombosis because of advanced age or previous history of thrombotic complications demonstrated that platelet cytoreduction with hydroxyurea is effective in reducing thrombotic complications. Other cytoreducing agents that have been used in this disease include alkylating agents, recombinant interferon alpha, and anagrelide. The use of antiplatelet therapy is also controversial, and is most highly effective in patients with digital or cerebrovascular ischemic problems.     

A clinical study of the use of a combination of glucomannan with lactulose in the constipation of pregnancy

RATIONALE: Constipation is a problem frequently encountered during pregnancy as is excessive weight gain. Treatments of common use to control constipation are endowed with some drawbacks and they are not active in controlling weight increase. A preparation of lactulose and glucomannan in previous studies proved very effective and well tolerated in patients affected by stypsis and evidentiated also activity both in controlling excessive food intake and in correcting some metabolic imbalances regarding lipids and urea. MATERIAL AND METHODS: 50 pregnant females affected by constipation were treated with sachets containing a preparation of glucomannan (1.45 g) and lactulose (4.2 g) in a posology of 2 (1-4) sachets a day for 1-3 months. RESULTS: Treatment induced a return to normal frequency of weekly number of evacuations (4.9-5.8/week) and a parallel control of weight gain (within 20% of initial body weight). The latter finding seems to be related to hunger control induced by glucomannan at the gastric level which prevents an excessive food intake.