Cell cycle regulation of human pancreatic cancer by tamoxifen

BACKGROUND: Clinical trials have suggested a survival advantage for selected patients with metastatic pancreatic cancer treated with tamoxifen. We sought to identify the molecular mechanism by which tamoxifen inhibits human pancreatic cancer cell (HPCC) growth. METHODS: HPCCs were grown in tamoxifen and growth inhibition was determined by 3H-thymidine uptake and by the MTT assay; changes in cell viability were determined by cell counts. Cell cycle alterations were evaluated by FACS, and the induction of apoptosis was evaluated using the TUNEL assay. Total cellular RNA was isolated after tamoxifen treatment, and Northern blot analysis was performed for p21waf1. RESULTS: Tamoxifen inhibited HPCC growth as measured by inhibition of 3H-thymidine incorporation and by the MTT assay. However, there was no decrease in the total number of viable cells after 6 days of treatment with 10 microM of tamoxifen and no evident apoptosis, confirming the absence of a cytotoxic effect. Cell cycle analysis revealed cellular arrest in the G0/G1 phase, which correlated with p21waf1 mRNA upregulation in response to tamoxifen treatment. CONCLUSIONS: Tamoxifen inhibits HPCC growth by inducing G0/G1 arrest with an associated increase in p21waf1 mRNA expression. Tamoxifen is an effective inhibitor of HPCC growth in vitro and warrants further in vivo study.     

Analysis of DNA polymorphism detected by genomic fingerprinting based on phage M13 DNA, in populations of Bashkir and Komi

Hyperpolymorphism of minisatellite DNA, detected using the M13 bacteriophage DNA hybridization probe, was studied in three ethnographic groups of Bashkirs and in the Komi population. Bands from 2 to 20 kb were analyzed in hybridization patterns. A significant population difference was detected both in evaluation of the average number of hybridization fragments per individuals and in the distribution of frequency of some fractions. Thus, it seems possible to describe a set of so-called characteristic fractions for each population. According to the hybridization fragment frequency for the populations investigated, an index of genetic similarity was calculated. The possibility of using this kind of multiple polymorphism of DNA in population genetic investigations at the level of ethnic groups and peoples is discussed, and a conclusion is made about the necessity of searching for the most informative methods of analyzing the data obtained.     

Fluconazole susceptibility testing of Cryptococcus neoformans: comparison of two broth microdilution methods and clinical correlates among isolates from Ugandan AIDS patients

We compared the yeast nitrogen base (YNB) broth microdilution method with the National Committee for Clinical Laboratory Standards (NCCLS) M27-A microdilution reference method for measuring the in vitro susceptibility of Cryptococcus neoformans isolates to fluconazole. A total of 149 isolates of C. neoformans var. neoformans from Ugandan AIDS patients was tested by both methods. An overall agreement of 88% between the two microdilution methods was observed. All isolates grew well in both RPMI 1640 and YNB media, and MICs could be read after 48 h of incubation by both methods. The range of fluconazole MICs obtained with the YNB method was broader than that obtained with the NCCLS method. The extended range of MICs provided by the YNB method may be of clinical value, as it appears that the clinical outcome may be better among patients infected with strains inhibited by lower concentrations of fluconazole as determined by the YNB method. The YNB method appears to be a viable option for testing C. neoformans against fluconazole.     

Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes

BACKGROUND: Anesthesia personnel are at risk for occupational infection with bloodborne pathogens from contaminated percutaneous injuries (CPIs). Additional information is needed to formulate methods to reduce risk. METHODS: The authors analyzed CPIs collected during a 2-yr period at 11 hospitals, assessed CPI underreporting, and estimated risks of infection with human immunodeficiency virus and hepatitis C virus. RESULTS: Data regarding 138 CPIs were collected: 74% were associated with blood-contaminated hollow-bore needles, 74% were potentially preventable, 30% were considered high-risk injuries from devices used for intravascular catheter insertion or obtaining blood, and 45% were reported to hospital health services. Corrected for injury underreporting, the CPI rate was 0.27 CPIs per yr per person; per full-time equivalent worker, there were 0.42 CPIs/yr. The estimated average 30-yr risks of human immunodeficiency virus or hepatitis C virus infection per full-time equivalent are 0.049% and 0.45%, respectively. Projecting these findings to all anesthesia personnel in the United States, the authors estimate that there will be 17 human immunodeficiency virus infections and 155 hepatitis C virus infections in 30 yr. CONCLUSIONS: Performance of anesthesia tasks is associated with CPIs from blood-contaminated hollow-bore needles. Thirty percent of all CPIs would have been high-risk for bloodborne pathogen transmission if the source patients were infected. Most CPIs were potentially preventable, and fewer than half were reported to hospital health services. The results identify devices and mechanisms responsible for CPIs, provide estimates of risk levels, and permit formulation of strategies to reduce risks.     

Home management of bronchopulmonary dysplasia

Home oxygen was utilized in six infants with BPD with no complications. This program allowed for early discharge of the infants, resulting in a mean financial savings of $18,000 per infant and a more normal family environment for the babies.     

3-Chloro-1,2-Propanediol Derived Amino Alcohol in Protein Hydrolysates

In model aqueous solutions containing 3-chIoro-l,2-propanediol (arising by the interaction of hydrochloric acid with lipids in protein hydrolysate and ammonia, 3-amino-1,2-propanediol was found as the main reaction product together with smaller amounts of glycerol. The reaction mechanism of formation of these two compounds was outlined and discussed as well as the possibilities of formation of some other amino analogues of glycerol chlorohydrins. 3-Amino-1,2-pro-panediol was also identified in commercially available seasonings (hydrolyzed vegetable protein) being present in concentrations of 30 mg kg^-1.