Biomedical subjects

Michael R Lasarev

Publications and source records attributed to Michael R Lasarev.

5 recordsLinked to original sources

PubMed2006

Monocyclic and dicyclic hydrocarbons: structural requirements for proximal giant axonopathy.

The chromogenic and neurotoxic gamma-diketone 1,2-diacetylbenzene (1,2-DAB), but not its isomer 1,3-DAB, induces blue discoloration of tissues and urine, clustering of axonal microtubules and proximal neurofilament-filled axonal swellings in rodents. The remarkable chromogenic property of 1,2-DAB, a monocyclic aromatic hydrocarbon, arises from reaction with lysine residues of proteins and formation of dimeric and polymeric derivatives. Tetralin, a dicyclic solvent structurally related to acetyl ethyl tetramethyl tetralin, a chromogenic and neurotoxic agent, reportedly induces excretion of green urine, and causes neurological disturbances in humans. Monocyclic aromatic 1,2,4-triethylbenzene (1,2,4-TEB), but not its isomer 1,3,5-TEB, is also reportedly chromogenic and induces neurophysiological deficits in rodents consistent with axonal neuropathy, but without neuropathological confirmation. We treated 12-week-old C57Bl/6 mice by gavage with 300, 600, or 900 mg/kg/day 1,2,4-TEB, or equivalent doses of 1,3,5-TEB, 3 days/week, for up to 12 weeks, or intraperitoneally with 400 mg/kg/day tetralin, or 50 or 100 mg/kg/day of its alpha-tetralol analogue, 5 days/week, for up to 5 weeks. Animals treated with 1,2,4-TEB, but not 1,3,5-TEB, tetralin or alpha-tetralol, developed hind limb weakness, excreted greenish urine, and showed 1,2-DAB-like neuropathology. These findings support the hypothesis that 1,2-spaced ethyl (or acetyl) moieties on a benzene ring of hydrocarbons are required for hydrocarbons to induce chromogenic changes and proximal giant neurofilamentous axonopathy. Key molecular targets of these compounds likely reside in the axon where they serve to maintain normal cytoskeletal organization.

Animals↗

PubMed2005

Standardizing global gene expression analysis between laboratories and across platforms.

To facilitate collaborative research efforts between multi-investigator teams using DNA microarrays, we identified sources of error and data variability between laboratories and across microarray platforms, and methods to accommodate this variability. RNA expression data were generated in seven laboratories, which compared two standard RNA samples using 12 microarray platforms. At least two standard microarray types (one spotted, one commercial) were used by all laboratories. Reproducibility for most platforms within any laboratory was typically good, but reproducibility between platforms and across laboratories was generally poor. Reproducibility between laboratories increased markedly when standardized protocols were implemented for RNA labeling, hybridization, microarray processing, data acquisition and data normalization. Reproducibility was highest when analysis was based on biological themes defined by enriched Gene Ontology (GO) categories. These findings indicate that microarray results can be comparable across multiple laboratories, especially when a common platform and set of procedures are used.

Gene Expression Profiling↗

PubMed2003

Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes.

Growth of the fetal heart involves cardiomyocyte enlargement, division, and maturation. Insulin-like growth factor-1 (IGF-1) is implicated in many aspects of growth and is likely to be important in developmental heart growth. IGF-1 stimulates the IGF-1 receptor (IGF1R) and downstream signaling pathways, including extracellular signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K). We hypothesized that IGF-1 stimulates cardiomyocyte proliferation and enlargement through stimulation of the ERK cascade and stimulates cardiomyocyte differentiation through the PI3K cascade. In vivo administration of Long R3 IGF-1 (LR3 IGF-1) did not stimulate cardiomyocyte hypertrophy but led to a decreased percentage of cells that were binucleated in vivo. In culture, LR3 IGF-1 increased myocyte bromodeoxyuridine (BrdU) uptake by three- to five-fold. The blockade of either ERK or PI3K signaling (by UO-126 or LY-294002, respectively) completely abolished BrdU uptake stimulated by LR3 IGF-1. LR3 IGF-1 did not increase footprint area, but as expected, phenylephrine stimulated an increase in binucleated cardiomyocyte size. We conclude that 1) IGF-1 through IGF1R stimulates cardiomyocyte division in vivo; hyperplastic growth is the most likely explanation of IGF-1 stimulated heart growth in vivo; 2) IGF-1 through IGF1R does not stimulate binucleation in vitro or in vivo; 3) IGF-1 through IGF1R does not stimulate hypertrophy either in vivo or in vitro; and 4) IGF-1 through IGF1R requires both ERK and PI3K signaling for proliferation of near-term fetal sheep cardiomyocytes in vitro.

Animals↗

PubMed2002

Factor analysis of Gulf War illness: what does it add to our understanding of possible health effects of deployment?

The authors conducted factor analysis on survey data from 1,779 Persian Gulf War veterans. Their purposes were to: 1) determine whether factor analysis identified a unique "Gulf War syndrome" among veterans potentially exposed to chemical warfare agents; 2) compare the findings of factor analysis with those from an epidemiologic analysis of symptom prevalence; and 3) observe the behavior of factor analysis when performed on dichotomous data. The factor analysis identified three factors, but they were not unique to any particular deployment group. A unique pattern of illness was not found for the larger group of veterans potentially exposed to chemical warfare agents; however, veterans who had witnessed the demolition of chemical warfare agents at the Khamisiyah site in Iraq had a greater prevalence of dysesthesia. An analysis of the performance of dichotomous variables in factor analysis showed that the standard criteria used to determine the number of relevant factors and the dominant variables within them may be inappropriate. While Gulf War veterans appear to suffer an increased burden of illness, there is insufficient evidence to identify a unique syndrome in this population of deployed servicemen and women. Furthermore, the results provide evidence that factor analysis may make a limited contribution in this area of research.

Adult↗

PubMed2002

Determining levels of unawareness in dementia research.

Clinical methods used to determine unawareness in dementia exist; however, their applicability to empirical research is limited. The authors present a statistically derived approach to determining unawareness that addresses these limitations. Dementia patients (n=32) completed an awareness questionnaire. On an identical questionnaire, collateral sources (relatives or friends; n=32) provided their best estimate of participants' abilities. The authors compared cluster analysis, the proposed empirical approach, to a currently used standard deviation cutoff score approach. Cluster analysis included all participants, displayed sound statistical properties, and was more sensitive to between-group differences in psychotic symptoms than standard deviation cutoff. Cluster analysis appears more appropriate for understanding the overall spectrum of unawareness in dementia research.

Aged↗