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Biomedical subjects

D G Grier

Publications and source records attributed to D G Grier.

10 recordsLinked to original sources

The pathophysiology of HOX genes and their role in cancer.

The HOM-C clustered prototype homeobox genes of Drosophila, and their counterparts, the HOX genes in humans, are highly conserved at the genomic level. These master regulators of development continue to be expressed throughout adulthood in various tissues and organs. The physiological and patho-physiological functions of this network of genes are being avidly pursued within the scientific community, but defined roles for them remain elusive. The order of expression of HOX genes within a cluster is co-ordinated during development, so that the 3' genes are expressed more anteriorly and earlier than the 5' genes. Mutations in HOXA13 and HOXD13 are associated with disorders of limb formation such as hand-foot-genital syndrome (HFGS), synpolydactyly (SPD), and brachydactyly. Haematopoietic progenitors express HOX genes in a pattern characteristic of the lineage and stage of differentiation of the cells. In leukaemia, dysregulated HOX gene expression can occur due to chromosomal translocations involving upstream regulators such as the MLL gene, or the fusion of a HOX gene to another gene such as the nucleoporin, NUP98. Recent investigations of HOX gene expression in leukaemia are providing important insights into disease classification and prediction of clinical outcome. Whereas the oncogenic potential of certain HOX genes in leukaemia has already been defined, their role in other neoplasms is currently being studied. Progress has been hampered by the experimental approach used in many studies in which the expression of small subsets of HOX genes was analysed, and complicated by the functional redundancy implicit in the HOX gene system. Attempts to elucidate the function of HOX genes in malignant transformation will be enhanced by a better understanding of their upstream regulators and downstream target genes.

Animals↗

Sorting mesoscopic objects with periodic potential landscapes: optical fractionation.

Viscously damped objects driven through a periodically modulated potential energy landscape can become kinetically locked in to commensurate directions through the landscape, and thus can be deflected away from the driving direction. We demonstrate that the threshold for an object to become kinetically locked in to an array can depend exceptionally strongly on its size. When implemented with an array of holographic optical tweezers, this process provides the basis for a continuous and continuously optimized sorting technique for mesoscopic objects called "optical fractionation."

Cell Separation↗

Measuring a colloidal particle's interaction with a flat surface under nonequilibrium conditions. Total internal reflection microscopy with absolute position information.

A new and general approach is proposed to analyze the dynamics of a colloidal particle interacting with a nearby wall. This analysis can be used to determine the acting forces even when the system is non-stationary. As an illustration, we use total internal reflection microscopy to investigate the forces acting on a polystyrene sulfate latex particle as it is receding from a charged glass surface.

Journal Article↗

Pair interaction of charged colloidal spheres near a charged wall.

Although equally charged colloidal particles dispersed in clean water are expected to repel each other, an unexplained long-range attraction has consistently been reported for charged colloidal spheres confined by charged macroscopic surfaces. We present an alternative equilibrium measurement of the pair interaction energy for charged spheres near a single charged wall. Analyzing their radial distribution functions for different concentrations reveals a purely repulsive sphere-sphere interaction that is well described by a screened Coulomb potential.

Journal Article↗

Hydrodynamic coupling of two brownian spheres to a planar surface.

We describe direct imaging measurements of the collective and relative diffusion of two colloidal spheres near a flat plate. The bounding surface modifies the spheres' dynamics, even at separations of tens of radii. This behavior is captured by a stokeslet analysis of fluid flow driven by the spheres' and wall's no-slip boundary conditions. In particular, this analysis reveals surprising asymmetry in the normal modes for pair diffusion near a flat surface.

Colloids↗

Pollen-stigma adhesion in Arabidopsis: a species-specific interaction mediated by lipophilic molecules in the pollen exine.

To investigate the nature and role of cell adhesion in plants, we analyzed the initial step of pollination in Arabidopsis: the binding of pollen grains to female stigma cells. Here we show this interaction occurs within seconds of pollination. Because it takes place prior to pollen hydration, it also requires adhesion molecules that can act in a virtually dry environment. We developed assays that monitored adhesion of populations of pollen grains and individual cells. Adhesion between pollen and stigma cells is highly selective - Arabidopsis pollen binds with high affinity to Arabidopsis stigmas, while pollen from other species fails to adhere. Initial binding is independent of the extracellular pollen coat (tryphine), indicating that adhesion molecules reside elsewhere on the pollen surface, most likely within the exine walls. Immediately after pollination, the stigma surface becomes altered at the interface, acquiring a pattern that interlocks with the exine; this pattern is evident only with pollen from Arabidopsis and its close relatives. Purified exine fragments bind to stigma cells, and biochemical analyses indicate that this specific, rapid and anhydrous adhesion event is mediated by lipophilic interactions.

Arabidopsis↗

New age crystals.

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Chemistry Techniques, Analytical↗

Recognition and treatment of ethanol abuse in trauma patients.

OBJECTIVE: To evaluate physicians' recognition of possible ethanol-related complications in trauma patients, and to compare benzodiazepine requirements in patients with positive and negative blood-ethanol concentrations. DESIGN: Retrospective investigation. SETTING: University medical center (level I trauma center). PATIENTS: One hundred thirty-one trauma patients more than 18 years of age who were admitted for at least 24 hours. OUTCOME MEASURES: (1) Physicians' recognition of ethanol (EtOH) as a potential factor complicating patient recovery in trauma patients admitted with positive blood-EtOH concentrations. (2) The amount of benzodiazepines administered to trauma patients with positive EtOH-blood concentrations compared to trauma patients with no detectable EtOH in their blood. RESULTS: The presence of EtOH in the blood or the potential for EtOH withdrawal was mentioned in the progress notes of approximately one fourth of the patients with positive blood-EtOH concentrations. Thiamine was administered in 8.2% of patients with EtOH-related injuries. Benzodiazepine requirements were significantly higher in patients with positive versus negative blood-EtOH concentrations. CONCLUSIONS: Prompt recognition and charting of suspected ethanol abuse is recommended, in conjunction with prompt administration of thiamine. It should be anticipated that patients with positive blood-ethanol concentrations will require higher doses of benzodiazepines compared to trauma patients without ethanol-related injuries.

Adult↗