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Biomedical subjects

P E Carroll

Publications and source records attributed to P E Carroll.

9 recordsLinked to original sources
PubMed2000

Synergistic induction of centrosome hyperamplification by loss of p53 and cyclin E overexpression.

Centrosome hyperamplification and the consequential mitotic defects contribute to chromosome instability in cancers. Loss or mutational inactivation of p53 has been shown to induce chromosome instability through centrosome hyperamplification. It has recently been found that Cdk2-cyclin E is involved in the initiation of centrosome duplication, and that constitutive activation of Cdk2-cyclin E results in the uncoupling of the centrosome duplication cycle and the DNA replication cycle. Cyclin E overexpression and p53 mutations occur frequently in tumors. Here, we show that cyclin E overexpression and loss of p53 synergistically increase the frequency of centrosome hyperamplification in cultured cells as well as in tumors developed in p53-null, heterozygous, and wildtype mice. Through examination of cells derived from Waf1-null mice, we further found that Waf1, a potent inhibitor of Cdk2-cyclin E and a major target of p53's transactivation function, is involved in coordinating the initiation of centrosome duplication and DNA replication, suggesting that Waf1 may act as a molecular link between p53 and Cdk2-cyclin E in the control of the centrosome duplication cycle.

Animals↗
PubMed1999

Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression.

We have previously reported that loss of p53 tumor suppressor protein results in centrosome hyperamplification, which leads to aberrant mitosis and chromosome instability. Since p53 is either deleted or mutated in human cancers at a high frequency, we investigated whether human cancers showed centrosome hyperamplification. Screening of advanced stage breast ductal carcinomas and squamous cell carcinomas of the head and neck (SCCHN) revealed that centrosome hyperamplification is frequent in both tumor types. Moreover, through the analyses of p53 in SCCHN samples by direct sequencing and by loss-of-heterozygosity test, we found that p53 mutations correlated with occurrence of centrosome hyperamplification. However, in some cases, we observed centrosome hyperamplification in tumors that retained wild-type p53. These tumors contained high levels of Mdm2. Since Mdm2 can inactivate p53 through physical association, we investigated whether Mdm2 overexpression induced centrosome hyperamplification. We found that Mdm2 overexpression, like loss of p53, induced centrosome hyperamplification and chromosome instability in cultured cells.

3T3 Cells↗
PubMed1993

Mergers of healthcare facilities: impact upon materiel management.

Hospital mergers afford healthcare providers the chance to take advantage of economies of scale, integrate clinical, administrative and support functions, eliminate functional redundancies and redesign patient care delivery. This article explains how such advantages were realized, demonstrated through a hypothetical case based on information obtained from actual mergers. A corporate materiel management division was established, and centralized warehousing, product evaluation and purchasing instituted. Some management positions were eliminated or restructured and patient care services were closed, relocated, or opened among the various entities in the merger. Through these and other changes, the new healthcare system was about to realize about $1.7 million in one-time savings and expects savings in the seven digits over at least the next three years. The article concludes that as hospital mergers continue to increase, the position of corporate director of materiel management will evolve as the next logical career step for materiel management professionals.

Bed Occupancy↗
PubMed1987

Materials management: stretching the "household" budget.

As CFOs assume responsibility for the materials management function because of the potential to maximize cash flow, achieve economies of scale, decrease costs, and streamline operations, they look for guidelines to evaluate performance. Conducting a systems operations audit can aid in assessing that performance. CFOs can determine whether materials management processes are working "smarter, nor harder."

Communication↗
PubMed1975

Chrysotherapy: pharmacological and clinical correlates.

Relationships between gold administration and serum gold content were observed in 56 RA subjects receiving up to five years of weekly chrysotherapy. Wide fluctuations in serum gold responses to standard 50 mg IM injections were noted. Individual adjustments to dosage schedules were made as dictated by patient serum gold responses. Enhanced clinical and laboratory response was prolonged with higher sustained serum gold concentration greater than 300 mug per cent. Maintaining serum levels greater than 300 mug per cent is postulated to facilitate access of gold to "effector sites" within the deeper compartments by providing higher sustained gradients between superficial (blood) and deeper body compartments. The complexity of the system of effector sites responsive to gold and their divergent location within the body likely affects the accessibility of the agent for these sites; hence, affecting the correlation between gold levels and therapeutic response. The application of pharmacokinetic principles in chrysotherapy, nevertheless, provides the basis for optimizing accessibility of the agent and the therapeutic response. (J Rheumatol 2: 401-410, 1975).

Arthritis, Rheumatoid↗