Imatinib mesylate (Gleevec) downregulates telomerase activity and inhibits proliferation in telomerase-expressing cell lines.

Imatinib mesylate (IM) is a tyrosine kinase inhibitor, which inhibits phosphorylation of downstream proteins involved in BCR-ABL signal transduction. It has proved beneficial in treating patients with chronic myeloid leukaemia (CML). In addition, IM demonstrates activity against malignant cells expressing c-kit and platelet-derived growth factor receptor (PDGF-R). The activity of IM in the blastic crisis of CML and against various myeloma cell lines suggests that this drug may also target other cellular components. In the light of the important role of telomerase in malignant transformation, we evaluated the effect of IM on telomerase activity (TA) and regulation in various malignant cell lines. Imatinib mesylate caused a dose-dependent inhibition of TA (up to 90% at a concentration of 15 microM IM) in c-kit-expressing SK-N-MC (Ewing sarcoma), SK-MEL-28 (melanoma), RPMI 8226 (myeloma), MCF-7 (breast cancer) and HSC 536/N (Fanconi anaemia) cells as well as in ba/F3 (murine pro-B cells), which do not express c-kit, BCR-ABL or PDGF-R. Imatinib mesylate did not affect the activity of other DNA polymerases. Inhibition of TA was associated with 50% inhibition of proliferation. The inhibition of proliferation was associated with a decrease in the S-phase of the cell cycle and an accumulation of cells in the G2/M phase. No apoptosis was observed. Inhibition of TA was caused mainly by post-translational modifications: dephosphorylation of AKT and, to a smaller extent, by early downregulation of hTERT (the catalytic subunit of the enzyme) transcription. Other steps of telomerase regulation were not affected by IM. This study demonstrates an additional cellular target of IM, not necessarily mediated via known tyrosine kinases, that causes inhibition of TA and cell proliferation.

Productive replication of caprine arthritis-encephalitis virus is associated with induction of apoptosis.

Caprine arthritis-encephalitis virus (CAEV), an ungulate lentivirus, causes a natural infection in goats. The present report demonstrates that in vitro, CAEV infection is associated with apoptosis, characterized by morphological changes such as condensation of chromatin and the appearance of apoptotic bodies. The presence of DNA fragments was documented by the appearance of a DNA 'ladder' in agarose gel electrophoresis, as well as by in situ end-labelling of DNA ends. In addition, flow cytometric analyses revealed the presence of a hypodiploid peak that gradually appeared as virus infection progressed.

On the Location of the Sensation Seeking construct in the Personality Domain.

The purpose of the study was to examine the location of Zuckerman's sensation seeking (SS) construct in the personality domain as measured by Cattell's 16 personality factors (16PF). The results of the factor analytic study indicated that the global construct of sensation seeking is related to the broad personality factor of independence. When the Sensation Seeking Scale (SSS) was divided into subscales, relations with two other broader personality factors, superego and pathemia, emerged as well. Nevertheless, the relationship with independence remained the most dominant one. The results of the present study seem to locate the sensation-seeking construct in the personality domain more precisely than previous findings.

Contradictory Or Complementary? Reassessment Of Two Competing Theories Of The Structure Of Attitudes.

The theories of Kerlinger and Eysenck on the nature of the dimensions underlying social attitudes are discussed. Integrating principles from both theories, an alternative approach to the issue is suggested and tested on the domain of attitudes towards education in relation to personality. The results of a multivariate analysis support Kerlinger's concept of the duality (vs. bipolarity) of the attitudinal domain, as well as Eysenck's theory about the reflection of personality on attitudes.

Altered bacteriophage T4 ribonucleic acid metabolism in a ribonuclease II-deficient mutant of Escherichia coli.

Some early T4 ribonucleic acids were not found in an infected ribonuclease II-deficient strain but were formed in ribonuclease II+ transductants as well as in wild-type Escherichia coli.

Checking the reliability and validity of HSPQ profiles.

Developed a scale designed to detect invalid response patterns on the High School Personality Questionnaire (HSPQ). Using a large sample of protocols drawn from the HSPQ standardization group, ten items were found to satisfy the necessary criterion for inclusion in the resulting "random" or "validity" (RV) scale. When applied to separate cross-validation groups of nearly 2,000 valid and randomly generated response protocols, RV was found to correctly classify 79% of the profiles. As a further test of the scale's utility, 100 profiles classified as valid and 100 classified as invalid were selected for comparison. In the invalid group, KR-20 reliabilities of the 14 trait scales were almost uniformly lowered, Also, for the invalid group the correlations among the trait scales were attenuated and altered to the extent that the underlying factor structure of the test was upset.

30 S pre-ribosomal RNA of Escherichia coli:primary and secondary processing.

The metabolism of newly-formed labeled 30 S pre-ribosomal RNA was studied in the Escherichia coli mutant strain AB301-105. Detailed kinetic analysis in rifampicin-treated cells showed that precursors of 23 S and 16 S rRNA are formed from the 30 S RNA species, even in phosphate-limited cultures. To establish the order fo segments along 30 S pre-rRNA, it was allowed to accumulate in replicate chloramphenicol-treated cultures, and pulse-labeled after the addition of rifampicin in segments that progressively contained more 3'-distal label with time. The purified RNAs from the various cultures were then cleaved to a limited extent by RNAase III; the specific activity of the fragments yielded an order from the 5'-end of 17.5S-X-25S, where X refers to some of the sequences released as additional small fragments. More extensive treatment the 25-S and 17.5-S pre-rRNA chains with RNAase III yielded additional fragments and produced RNA species with the mobility of the 23-S and 16-S RNA precursors made in normal cells treated with chloramphenicol. A processing scheme is suggested that distinguishes between early, site-specific cleavage of recognition sites in the RNA itself ('primary processing'), and later, "secondary processing' reactions. The secondary processing reactions are blocked chloramphenicol-treated wild-type cells.