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Biomedical subjects

A A Avilion

Publications and source records attributed to A A Avilion.

4 recordsLinked to original sources

Tetrahymena telomerase RNA levels increase during macronuclear development.

Telomeres, the G-rich sequences found at the ends of eukaryotic chromosomes, ensure chromosome stability and prevent sequence loss from chromosome ends during DNA replication. During macronuclear development in Tetrahymena, the chromosomes fragment into pieces ranging from 20 kb to 1,500 kb. Tetrahymena telomerase, a ribonucleoprotein, adds telomeric (TTGGGG)n repeats onto telomeres and onto the newly generated macronuclear DNA ends. We have investigated whether telomerase RNA levels increase during macronuclear development, since such an increase might be expected during chromosomal fragmentation. The steady-state level of the telomerase RNA component was used to estimate the abundance of telomerase present in mating and nonmating Tetrahymena. Northern blot analysis revealed that in vegetatively growing Tetrahymena, there were 18,000-40,000 copies of telomerase RNA per cell. In mating cultures, the levels of RNA increased 2- to 5-fold at 9-15 h, and 1.5- to 3.5-fold in starved nonmating cultures. This increase in telomerase RNA paralleled telomerase activity, which also increased slightly in mating and starved nonmating cells.

Animals

Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.

Loss of telomeric DNA during cell proliferation may play a role in ageing and cancer. Since telomeres permit complete replication of eukaryotic chromosomes and protect their ends from recombination, we have measured telomere length, telomerase activity and chromosome rearrangements in human cells before and after transformation with SV40 or Ad5. In all mortal populations, telomeres shortened by approximately 65 bp/generation during the lifespan of the cultures. When transformed cells reached crisis, the length of the telomeric TTAGGG repeats was only approximately 1.5 kbp and many dicentric chromosomes were observed. In immortal cells, telomere length and frequency of dicentric chromosomes stabilized after crisis. Telomerase activity was not detectable in control or extended lifespan populations but was present in immortal populations. These results suggest that chromosomes with short (TTAGGG)n tracts are recombinogenic, critically shortened telomeres may be incompatible with cell proliferation and stabilization of telomere length by telomerase may be required for immortalization.

Cell Transformation, Neoplastic

Nuclear formation in a Drosophila cell-free system.

A cell-free preparation obtained from 0- to 5-h-old Drosophila melanogaster embryos induces chromatin decondensation and nuclear formation from demembranated Xenopus sperm. Newly formed nuclei have a peripheral lamina, a double membrane, and structures resembling pore complexes. Indirect immunofluorescence analyses demonstrate the association of Drosophila lamins and DNA topoisomerase II with newly assembled nuclei.

Animals

Endogenous cholecystokinin does not decrease food intake or gastric emptying in fasted rats.

To investigate the hypothesized inhibitory effect of cholecystokinin (CCK) released from the small intestine on food intake and gastric emptying, we infused soybean trypsin inhibitor (STI) into the stomach or duodenum of male rats deprived of food for 17 h. Intraduodenal infusions of STI (100-200 mg) before real or sham feeding, or during sham feeding, had no effect on food intake. Intragastric infusions of STI (100-200 mg) also had no effect on gastric emptying. Identical infusions of STI, however, increased bioassayable plasma CCK six to ninefold. The failure of endogenous, small intestinal CCK released by STI to decrease food intake or to decrease gastric emptying is evidence against the hypothesis that the inhibitions of food intake and of gastric emptying are physiological functions of small intestinal CCK in food-deprived rats. In contrast to the negative results with STI, administration of exogenous CCK-8 (2-4 micrograms/kg ip) significantly inhibited food intake and gastric emptying despite producing smaller increases of plasma CCK than STI produced. The reason for the differential effects of exogenous and endogenous CCK is not clear and requires further investigation.

Animals