Neoplastic meningosis in immature cell leukemias and malignant lymphomas

162 patients with acute leukemias or malignant non-Hodgkin lymphomas were examined for meningeal and cerebral manifestations of their disease. A clinically manifest disease could be found in 13 patients, meningosis was additionally detected by autopsy in 32 patients. The highest frequency was found in acute lymphatic leukemia followed by lymphoblastic lymphomas and acute myeloic leukemias. Less frequently there was a meningeal involvement in low-grade malignant lymphomas which becomes clinically manifest only in some rare cases. In this respect, non-lymphoblastic, high grade-malignant lymphomas take an intermediate position. On principle, meningosis prophylaxis is imperative for acute lymphoblastic leukemias and advanced lymphoblastic lymphomas.     

Major acute phase alpha 1-protein of the rat is homologous to bovine kininogen and contains the sequence for bradykinin: its synthesis is regulated at the mRNA level

The complete amino acid sequence of major acute phase alpha 1-protein of the rat (MAP) was derived from the nucleotide sequence of cloned cDNA. Amino acid analysis and partial sequencing supported the predicted sequence. The amino acid compositions of MAP and rat low-Mr kininogen are identical within experimental variation. The sequence is homologous (60%) to that of bovine low-Mr kininogen and both proteins carry the sequence for the vasoactive nonapeptide bradykinin in their C-terminal region. The rate of synthesis of MAP and the levels of MAP mRNA change coordinately during the acute phase response to inflammation.     

Sesquiterpenoids from the liverwort Lophozia ventricosa

Two sesquiterpenoids, previously reported as ventricosins A and B, from Lophozia ventricosa have been identified as ent-4(15),7(11)-eudesmadien-8-one and ent-maalioxide, respectively.     

Highly immunogenic regressor tumor cells can prevent development of postsurgical tumor immunity

Highly immunogenic malignant cells form small tumors that spontaneously regress after initial growth because the tumor induces specific immunity. However, variants may arise during the initial tumor growth that lose antigens, grow progressively, often become the predominant tumor population, and eventually kill the host. These progressively growing variants usually have not lost all tumor antigens and remain susceptible to rejection by T cells specific for antigens present on the parental tumor and retained by the progressively growing variants. Thus, it would seem logical for therapy to actively immunize with the parental highly immunogenic tumor (or sublines made similarly immunogenic by tumor heterogenization) after maximal surgical removal of the growing tumor. However, the present findings suggest that such a strategy may be ineffective and have adverse effects: the parental highly immunogenic tumor cells, either remaining or reintroduced, may perpetuate unresponsiveness to both the parental and the variant tumor. These findings suggest that unless tumor-induced suppression is first abrogated, immunization with highly immunogenic tumor cells may be counterproductive because this maneuver may maintain preexisting immune suppression and prevent development of postsurgical tumor immunity.     

A non-mitogenic analogue of epidermal growth factor enhances the phosphorylation of endogenous membrane proteins

The cyanogen bromide cleaved analogue of Epidermal Growth Factor (EGF) binds to EGF receptors with reduced affinity but fails to induce DNA synthesis. However, at similar receptor occupancy, cyanogen bromide cleaved EGF is as potent as EGF in enhancing the phosphorylation of endogenous membrane proteins mediated by the EGF specific, cyclic nucleotide independent protein kinase. Two possibilities arise concerning the biological role of the EGF induced membrane protein phosphorylation: 1) it is not related to the triggering of DNA synthesis by EGF and does not serve as “second messenger” for the growth factor. 2) it is a necessary but not sufficient biochemical signal for the activation of DNA synthesis by EGF.     

Recovering motifs from biased genomes: application of signal correction

A significant problem in biological motif analysis arises when the background symbol distribution is biased (e.g. high/low GC content in the case of DNA sequences). This can lead to overestimation of the amount of information encoded in a motif. A motif can be depicted as a signal using information theory (IT). We apply two concepts from IT, distortion and patterned interference (a type of noise), to model genomic and codon bias respectively. This modeling approach allows us to correct a raw signal to recover signals that are weakened by compositional bias. The corrected signal is more likely to be discriminated from a biased background by a macromolecule. We apply this correction technique to recover ribosome-binding site (RBS) signals from available sequenced and annotated prokaryotic genomes having diverse compositional biases. We observed that linear correction was sufficient for recovering signals even at the extremes of these biases. Further comparative genomics studies were made possible upon correction of these signals. We find that the average Euclidian distance between RBS signal frequency matrices of different genomes can be significantly reduced by using the correction technique. Within this reduced average distance, we can find examples of class-specific RBS signals. Our results have implications for motif-based prediction, particularly with regards to the estimation of reliable inter-genomic model parameters.     

Noxa1 is a central component of the smooth muscle NADPH oxidase in mice

NADPH oxidase is the most important source of oxygen-derived radicals (ROS) in the vascular wall. In vascular smooth muscle cells (VSMC), NADPH oxidase is characterized by the expression of the membrane subunit Nox1, which is activated by cytoplasmic proteins binding to its activation domain. We set out to identify the cytoplasmic protein involved in NADPH oxidase activation in mouse VSMC. Western blot analysis revealed that human endothelial cells and leukocytes but not VSMC from the aorta of the rat and the mouse express the classic NADPH oxidase activator p67phox. In mouse VSMC, however, the p67phox homologue Noxa1 was detected. Using antibodies generated against mouse Noxa1, the protein was observed in the cytosolic fraction of mouse VSMC with a molecular weight of about 51 kDa. Immunohistochemistry revealed that Noxa1 is expressed in the smooth muscle layer but not in endothelium or the adventitia of the mouse carotid artery. Fluorescent fusion proteins of Noxa1 were observed to be expressed in the cytoplasm of VSMC and coexpression of the NADPH oxidase organizer Noxo1 targeted the complex to membrane. An antisense plasmid of Noxa1 attenuated the endogenous Noxa1 protein expression in VSMC. This plasmid attenuated the ROS formation in mouse VSMC as detected using L012 chemiluminescence and prevented the agonist-induced ROS production in response to basic fibroblast growth factor and epidermal growth factor. In conclusion, these data indicate that Noxa1 replaces p67phox in VSMC and plays a central role in the activation of the NADPH oxidase in the vascular wall.