An Improved Method for the Synthesis of the of Indole[2,3-a]Pyrrolo[3,4-c]Carbazole-5,6-Dione N-Glycosides and their Cytotoxic Activity

Pharmaceutical Chemistry Journal - Use of formylindolylacetic acid as a reagent at the stage of preparing the glycosides of bis(indolyl)furan-2,5-diones and dioxane as solvent increased yields from...     

Comparative investigation of the long non-coding M-F genome region of wild-type and vaccine measles viruses

Summary.  The sequence of the 300 nucleotides region of the measles virus genome was determined that includes a part of the 3′-untranslated region of the matrix (M) gene, the intergenic region and a part of the 5′-untranslated region of the fusion (F) gene [M-F region] for vaccine strain Leningrad-16 and 14 wild-type isolates. The data obtained demonstrate the variability of this long non-coding M-F region. No mutations in this region of the genome were found which seem to be specific for vaccine strains of measles virus (MV). Accepted August 1, 1997 Received June 2, 1997     

Comparative mapping of X chromosomes in vole species of the genus Microtus

Comparative mapping of X-linked genes has progressed rapidly since Ohno's prediction that genes on the X chromosome should be conserved as a syntenic group in all mammals. Although several conserved blocks of homology between human and mouse have been discovered, rearrangements within the X chromosome have also been characterized. More recently, some exceptions to Ohno's law have been reported. We have used fluorescence in situ hybridization (FISH) to map five genes, Gla, G6pd, Hprt, Pgk1 and Xist, to two of the largest conserved segments of X material in five members of the genus Microtus (grey vole) and show that vole X chromosomes demonstrate greater homology to human than to mouse. Cytogenetic analysis indicates a relatively high frequency of rearrangement during vole evolution, although certain blocks of homology appear to be highly conserved in all species studied to date. On this basis we were able to predict the probable location of the rat X inactivation centre (Xic) based solely on high-resolution G-banding. Our prediction was then confirmed by mapping the rat Xist gene by FISH. The possible significance of conserving long-range chromosome structure in the vicinity of the Xic is discussed with respect to the mechanism of X inactivation.     

Effects of aging on hypothalamic-pituitary-adrenal system function in non-human primates

The study was aimed at characterizing the changes in hypothalamic-pituitary-adrenal (HPA) axis function during aging in monkey models (Papio hamadryas and Macaca mulatta). It has been established by specific radioimmunoassay and enzyme immunoassay that basal plasma levels of adrenal androgenes (dehydroepiandrosterone-DHEA, dehydroepiandrosterone sulfate-DHEAS) and the early precursors of steroid hormones (pregnenolone and 17-hydroxypregnenolone) progressively decrease with age in baboons and macaques, while cortisol and 11-desoxycortisol concentrations do not change. The old female rhesus monkeys exhibited a higher cortisol and corticosterone response, but a lower DHEAS response to corticotropin-releasing hormone (CRH) administration then the young monkeys. The aged rhesus monkeys also exhibited a decrease of the adrenal cortex resiliency, that was manifested in the deceleration of the decrease of cortisol concentrations after the peak values had been reached in response to ACTH 1-39 administration. At the same time the ACTH 1-24 depot test revealed no age-related changes in the maximum capacity of monkey adrenals to synthesize and secrete cortisol. The aged monkeys also developed less sensitivity of the HPA axis to dexametasone suppression test. The age-related hormonal changes may play an important role in the age-related involutive processes and in the disorders of the adaptive ability of old organisms.     

Chromosomal evolution of Arvicolinae (Cricetidae, Rodentia). II. The genome homology of two mole voles (genus Ellobius), the field vole and golden hamster revealed by comparative chromosome painting

Using cross-species chromosome painting, we have carried out a comprehensive comparison of the karyotypes of two Ellobius species with unusual sex determination systems: the Transcaucasian mole vole, Ellobius lutescens (2n = 17, X in both sexes), and the northern mole vole, Ellobius talpinus (2n = 54, XX in both sexes). Both Ellobius species have highly rearranged karyotypes. The chromosomal paints from the field vole (Microtus agrestis) detected, in total, 34 and 32 homologous autosomal regions in E. lutescens and E. talpinus karyotypes, respectively. No difference in hybridization pattern of the X paint (as well as Y paint) probes on male and female chromosomes was discovered. The set of golden hamster (Mesocricetus auratus) chromosomal painting probes revealed 44 and 43 homologous autosomal regions in E. lutescens and E. talpinus karyotypes, respectively. A comparative chromosome map was established based on the results of cross-species chromosome painting and a hypothetical ancestral Ellobius karyotype was reconstructed. A considerable number of rearrangements were detected; 31 and 7 fusion/fission rearrangements differentiated the karyotypes of E. lutescens and E. talpinus from the ancestral Ellobius karyotype. It seems that inversions have played a minor role in the genome evolution of these Ellobius species.     

Increased Fas expression reduces the metastatic potential of human osteosarcoma cells.

PURPOSE: The process of metastasis requires the single tumor cell that seeds the metastatic clone to complete a complex series of steps. Identifying factors responsible for these steps is essential in developing and improving targeted therapy for metastasis. Resistance to receptor-mediated cell death, such as the Fas/Fas ligand pathway, is one mechanism commonly exploited by metastatic cell populations. EXPERIMENTAL DESIGN AND RESULTS: LM7, a subline of the SAOS human osteosarcoma cell line with low Fas expression, was selected for its high metastatic potential in an experimental nude mouse model. When transfected with the full-length Fas gene (LM7-Fas), these cells expressed higher levels of Fas than the parental LM7 cells or LM7-neo control-transfected cells. These cells were also more sensitive to Fas-induced cell death than controls. When injected intravenously into nude mice, the LM7-Fas cell line produced a significantly lower incidence of tumor nodules than control cell lines. Lung weight and tumor nodule size were also decreased in those mice injected with LM7-Fas. Levels of Fas were quantified in osteosarcoma lung nodules from 17 patients. Eight samples were Fas negative, whereas the remaining 9 were only weakly positive compared with normal human liver (positive control). CONCLUSIONS: Our results demonstrate that altering Fas expression can impact the metastatic potential of osteosarcoma cells. We conclude that the increase of Fas on the surface of the LM7 osteosarcoma cells increased their sensitivity to Fas-induced cell death in the microenvironment of the lung, where Fas ligand is constitutively expressed. Thus, loss of Fas expression is one mechanism by which osteosarcoma cells may evade host resistance mechanisms in the lung, increasing metastatic potential. Fas may therefore be a new therapeutic target for osteosarcoma.     

Role of Coronary Flow Velocity in Predicting Adverse Outcome in Clinical Practice

There is a lack of information on the prognostic value of local high velocity in coronary arteries during echocardiography. The aim of the study described here was to define the prognostic value of local velocity >70?cm/s in the left main, anterior or circumflex artery during echocardiography. There were 412 patients in the prospective study. Death, non-fatal myocardial infarction, acute pulmonary edema, acute coronary syndrome and revascularization were defined as major adverse cardiac events (MACEs). Over 10.5?mo, there were 207 patients with MACEs. Seventeen patients died, 10 had non-fatal acute cardiac events and 184 underwent revascularization. Deaths occurred in patients with high local velocity (6.4% vs. 0%, p?<0.009). Acute cardiac events occurred in 10% versus 0% (p?<0.003). MACEs were observed in 62% versus 0% (p?<0.0000001). Only maximal velocity was an independent prognostic predictor of death (odds ratio?=?1.02, 95% confidence interval: 1.01–1.03, p?<0.02) and MACEs (odds ratio?=?1.04, 95% confidence interval: 1.02–1.05, p?<0.0001). The success rate of coronary artery visualization for at least one segment was 91%.