Synthesis and antiviral activity evaluation of 3'-fluoro-3'-deoxyribonucleosides: broad-spectrum antiviral activity of 3'-fluoro-3'-deoxyadenosine

Five 3'-fluorinated ribonucleosides were prepared and evaluated for their inhibitory properties against different viruses. The synthesis of these compounds was achieved by treatment of 2',5'-di-O-tritylated nucleoside analogues possessing a xylo-configuration with diethylaminosulfur trifluoride, followed by deprotection. 3'-Fluoro-3'-deoxyadenosine was active against a broad range of viruses, encompassing both DNA viruses [pox (vaccinia)], single-stranded (+) RNA viruses [picorna (polio, Coxsackie B), toga (sindbis, Semliki Forest)] and double-stranded RNA viruses (reo). In its antiviral activity spectrum 3'-fluoro-3'-deoxyadenosine clearly differed from those adenosine analogues that are known as inhibitors of S-adenosylhomocysteine hydrolase. 3'-Fluoro-3'-deoxyadenosine also proved effective in vivo, in inhibiting tail lesion formation in mice inoculated intravenously with vaccinia virus.     

Physiologische Reaktionen nach der Blutentnahme

Zusammenfassung Zur Prüfung einer von den Amerikanernvan Slyke undPhillips angegebenen Schnellmethode zur Messung des menschlichens Bluteiweißes wurden 50 Blutspender untersucht und ihre physiologischen Reaktionen nach der Blutentnahme geprüft.Es konnte bestätigt werden, daß beim Blutverlust der Verringerung der kreisenden Blutmenge die entscheidende Bedeutung zukommt. Der Organismus ist bestrebt, die Leere im Kreislauf durch Ausschüttung hämoglobinreicherer Erythrocyten aus den Depotorganen, wie Leber, Milz und subpapillärem Plexus aufzufüllen.Durch Einströmen von Gewebswasser in die Blutbahn kehrt das Kreislaufvolumen zur ursprünglichen Norm zurück, die Erythrocyten verschwinden wieder in ihre Lagerstätten.Zur Erhaltung des kolloidosmotischen Druckes, d. h. zur Retention der eiweißärmeren Gewebsflüssigkeit, werden hydrationsfähige Proteine aus der Leber vornehmlich mobilisiert.Die Wiederauffüllung des Kreislaufs ist in erster Linie eine physikalische Notwendigkeit, zu deren Stabilisierung Gewebs- wie Plasmaproteine beitragen. Das weitere Absinken der Erythrocyten über den 2. Tag hinaus wird mit ihrem hohen Eiweißmolekül erklärt, das in den ersten Tagen nach der Blutentnahme als Plasmaprotein Verwendung findet.Die Tatsache, daß die hier gefundenen Ergebnisse mit bisherigen übereinstimmen, verbunden mit dem Vorteil der sicheren und schnellen Handhabung, lassen die Methode vonvan Slyke undPhillips für die Klinik brauchbar erscheinen.Mit 4 Textabbildungen.     

Characterization and Development of UCI 107, a Primary Human Ovarian Carcinoma Cell Line

We introduce a new epithelial ovarian carcinoma cell line (UCI 107) from a patient with papillary adenocarcinoma of the ovary who had not been previously treated. The growth characteristics, chemosensitivity, tumorgenicity, cytogenetics, antigen expression, and receptor status were examined. A standardized photometric assay was implemented to determine the response to single drug agents including doxorubicin (ADR), cisplatin (CDDP), and Taxol. Tumorgenicity was determined utilizing female athymic mice implanted either subcutaneously (sc) or intraperitoneally (ip) with 1 × 10⁷ UCI 107 cells. UCI 107 cells grow rapidly in culture with lag phase of approximately 48 hr, population doubling time of 24-36 hr, and saturation density of 4.8 × 10⁵ cells/cm². The 50% inhibitory concentration values for the chemotherapeutic agents were 0.170, 0.029, and 0.330 μM for ADR, Taxol, and CDDP, respectively. Nude mice produced ip tumors within 15 days, resulting in death from carcinomatosis 40-45 days postimplantation. Subcutaneous tumor nodules (100 mm³ were observed in nude mice 12-13 days post-tumor implantation reaching a maximum tumor volume of approximately 10,000 mm³ by Day 30. The cytogenetic composite karyotype is as follows: 46, X, der (X) t (X;7) (p11;q22), inv dup (1) (q12;q32), t (6;6;11;22) (p21.3;q16;q23.3;q13.3), del (13) (q14.1). The cell line expresses progesterone receptor, increased levels of p53 protein, and cytokeratins. It does not appear to express Her-2/neu protein, estrogen receptor, nor the CA 125 tumor marker. In conclusion, UCI 107 displays unique cellular properties which make it an attractive model for the study of ovarian cancer.     

Physical inactivity, excess adiposity and premature mortality

The purpose of this report is to review the evidence that physical inactivity and excess adiposity are related to an increased risk of all‐cause mortality, and to better identify the independent contributions of each to all‐cause mortality rates. A variance‐based method of meta‐analysis was used to summarize the relationships from available studies. The summary relative risk of all‐cause mortality for physical activity from the 55 analyses (31 studies) that included an index of adiposity as a covariate was 0.80 [95% confidence interval (CI) 0.78–0.82], whereas it was 0.82 [95% CI 0.80–0.84] for the 44 analyses (26 studies) that did not include an index of adiposity. Thus, physically active individuals have a lower risk of mortality by comparison to physically inactive peers, independent of level of adiposity. The summary relative risk of all‐cause mortality for an elevated body mass index (BMI) from the 25 analyses (13 studies) that included physical activity as a covariate was 1.23 [95% CI 1.18–1.29], and it was 1.24 [95% CI 1.21–1.28] for the 81 analyses (36 studies) that did not include physical activity as a covariate. Studies that used a measure of adiposity other than the BMI show similar relationships with mortality, and stratified analyses indicate that both physical inactivity and adiposity are important determinants of mortality risk.     

Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph-negative,BCR-positive patients with chronic myeloid leukemia

Leukemic cells from two patients with Philadelphia-negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M-BCR region and formation of BCR-ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR-ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph-positive CML and in almost all investigated CML with variant Ph or Ph-negative, BCR-positive cases. The few aberrant chromosomal localizations of BCR-ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR-ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph-negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley-Liss, Inc.