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Full-Text Articles in Life Sciences

Analysis Of Expansion Of Myeloid Progenitors In Mice To Identify Leukemic Susceptibility Genes, Vincent Sollars, Ed Pequignot, Jay Rothstein, Arthur Buchberg Aug 2012

Analysis Of Expansion Of Myeloid Progenitors In Mice To Identify Leukemic Susceptibility Genes, Vincent Sollars, Ed Pequignot, Jay Rothstein, Arthur Buchberg

Vincent E Sollars

The myeloid progenitor cell compartment (MPC) exhibits pronounced expansion in human myeloid leukemias. It is becoming more apparent that progression of myelodysplastic syndromes and myeloproliferative diseases to acute myelogenous leukemia is the result of defects in progenitor cell maturation. The MPC of bone marrow was analyzed in mice using a cell culture assay for measuring the relative frequency of proliferative myeloid progenitors. Response to the cytokines SCF, IL-3, and GMCSF was determined by this assay for the leukemic mouse strain BXH-2 and ten other inbred mouse strains. Significant differences were found to exist among ten inbred mouse strains in the …


Epigenetic Modification As An Enabling Mechanism For Leukemic Transformation, Vincent Sollars Aug 2012

Epigenetic Modification As An Enabling Mechanism For Leukemic Transformation, Vincent Sollars

Vincent E Sollars

Cancer is now thought of as a fundamentally genetic disease, in that changes in the genome result in aberrant gene expression of oncogenes and tumor suppressor genes to promote oncogenesis. However, with our increasing knowledge of gene regulation, it is becoming obvious that changes in nucleotide sequence are not the sole mechanism for eliciting changes in transcription. An additional layer of regulation of gene expression, called epigenetics, is now being realized as increasingly important in oncogenesis. Epigenetics is defined as non-sequence based changes in chromatin that elicit changes in gene expression that are propagated through mitosis and/or meiosis. The alleles …


Membrane Fusion Proteins Are Required For Oskar Mrna Localization In The Drosophila Egg Chamber, Douglas Ruden, Vincent Sollars, Xiaoyan Wang, Daisuke Mori, Marina Alterman, Xiangyi Lu Aug 2012

Membrane Fusion Proteins Are Required For Oskar Mrna Localization In The Drosophila Egg Chamber, Douglas Ruden, Vincent Sollars, Xiaoyan Wang, Daisuke Mori, Marina Alterman, Xiangyi Lu

Vincent E Sollars

We used a genetic screen in Drosophila to identify mutations which disrupt the localization of oskar mRNA during oogenesis. Based on the hypothesis that some cytoskeletal components which are required during the mitotic divisions will also be required for oskar mRNA localization during oogenesis, we designed the following genetic screen. We screened for P-element insertions in genes which slow down the blastoderm mitotic divisions. A secondary genetic screen was to generate female germ-line clones of these potential cell division cycle genes and to identify those which cause the mislocalization of oskar mRNA. We identified mutations in ter94 which disrupt the …


Diversity In Secreted Pla2-Iia Activity Among Inbred Mouse Strains That Are Resistant Or Susceptible To Apcmin/+ Tumorigenesis, Marina Markova, Revati Koratkar, Karen Silverman, Vincent Sollars, Melina Macphee-Pellini, Rhonda Walters, Juan Palazzo, Arthur Buchberg, Linda Siracusa, Steven Farber Aug 2012

Diversity In Secreted Pla2-Iia Activity Among Inbred Mouse Strains That Are Resistant Or Susceptible To Apcmin/+ Tumorigenesis, Marina Markova, Revati Koratkar, Karen Silverman, Vincent Sollars, Melina Macphee-Pellini, Rhonda Walters, Juan Palazzo, Arthur Buchberg, Linda Siracusa, Steven Farber

Vincent E Sollars

The secreted phospholipase A2 type IIA (Pla2g2a) gene was previously identified as a modifier of intestinal adenoma multiplicity in ApcMin/+ mice. To determine if intestinal secreted phospholipase A2 (sPLA2) activity was also attenuated in susceptible strains, we developed a sensitive assay to directly quantitate sPLA2 activity in the murine intestinal tract utilizing a fluorescent BODIPY-labeled phospholipid substrate. Here, we report assay conditions that distinguish between secreted and cytosolic PLA2 enzyme activities in extracts of intestinal tissue. The small intestine exhibited higher activity levels than the large intestine. Consistent with predictions from the sPLA …


A Drosophila Kinesin-Like Protein, Klp38b, Functions During Meiosis, Mitosis, And Segmentation, Douglas Ruden, Wei Cui, Vincent Sollars, Marina Alterman Aug 2012

A Drosophila Kinesin-Like Protein, Klp38b, Functions During Meiosis, Mitosis, And Segmentation, Douglas Ruden, Wei Cui, Vincent Sollars, Marina Alterman

Vincent E Sollars

We show that klp38B, isolated as a mutation that dominantly prolongs blastoderm mitotic cycles in Drosophila, encodes a Drosophila kinesin-like protein. Further genetic analyses show that Klp38B not only functions during mitosis, but is also required for meiosis and abdominal segmentation. Sequence comparisons suggest that Klp38B encodes an aminoterminal microtubule motor domain, a central a-helical coiled-coil domain, and a C-terminal globular domain. Evidence that Klp38B is required during meiosis is that flies transheterozygous for mutations in both klp38B and nod have a high frequency of 4th chromosome meiotic nondisjunction. Nod is a chromokinesin, a chromosome binding kinesin, that is believed …


17-N-Allylamino-17-Demethoxygeldanamycin Induces A Diverse Response In Human Acute Myelogenous Cells, Jennifer Napper, Vincent Sollars Aug 2012

17-N-Allylamino-17-Demethoxygeldanamycin Induces A Diverse Response In Human Acute Myelogenous Cells, Jennifer Napper, Vincent Sollars

Vincent E Sollars

The goal of this study was to ascertain the specific effects of 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG) treatment in human acute myelogenous leukemia (AML). Four human leukemia cell lines were treated with varying doses of 17-AAG followed by analysis of toxicity, apoptosis, proliferation, and cell cycle. Cell cycle analysis revealed that the cells accumulate in G2/M phase within 96 hours of treatment, although the effect was not equivalent among the cell lines. p21, p53 expression and MDR1 activity were among the possible mechanisms uncovered for the differing responses. Exploiting these differences may allow for more effective combinatory treatments in patients with AML.


A High Omega-3 Fatty Acid Diet Has Different Effects On Early And Late Stage Myeloid Progenitors, Melinda Varney, James Buchanan, Yulia Dementieva, W. Hardman, Vincent Sollars Aug 2012

A High Omega-3 Fatty Acid Diet Has Different Effects On Early And Late Stage Myeloid Progenitors, Melinda Varney, James Buchanan, Yulia Dementieva, W. Hardman, Vincent Sollars

Vincent E Sollars

The effects of the polyunsaturated omega-3 (n-3) and omega-6 (n-6) fatty acids (FA) on hematopoiesis are complex in that both FA forms are processed into leukotrienes, eicosanoids, and prostaglandins, which can have independent effects. These FA have antagonistic effects in that n-6 FA prostaglandins tend to be pro-proliferative and pro-inflammatory, while the effects of n-3 FA prostaglandins are the opposite. We have previously shown that diets high in n-3 FA reduce the size of the middle to later stage myeloid progenitor compartment in FVB X sv129 F1hybrid mice. To assay the effects of high n-3 FA diets on earlier stages …