Biomedical subjects

D Farrelly

Publications and source records attributed to D Farrelly.

At least 19 recordsLinked to original sources

PubMed2000

Transition state theory without time-reversal symmetry: chaotic ionization of the hydrogen atom

We present the first application of transition state theory to a system that evolves from an initial to a final state without time-reversal symmetry. The problem studied is the chaotic ionization of a hydrogen atom in crossed electric and magnetic fields. The stable manifolds of the transition state reveal a fractal tiling which connects the geometrical properties of the tiling to the ionization rate, leading to a theoretical explanation for the computational and experimental observation of "prompt" and "delayed" electrons in this problem.

Journal Article↗

PubMed2000

Stabilization of molecular atoms

We demonstrate the possibility of stabilizing the motion of ion-pair states through the use of external electric and magnetic fields. In conjunction with the Coulomb force, these fields can be engineered so as to lead to the creation of outer equilibrium points which can support non-spreading coherent wavepackets and long-lived states. Specific application is made to the H(+)-H- ion pair, recently investigated using threshold ion-pair production spectroscopy (TIPPS).

Journal Article↗

PubMed1999

Mice mutant for glucokinase regulatory protein exhibit decreased liver glucokinase: a sequestration mechanism in metabolic regulation.

The importance of glucokinase (GK; EC 2.7.1.12) in glucose homeostasis has been demonstrated by the association of GK mutations with diabetes mellitus in humans and by alterations in glucose metabolism in transgenic and gene knockout mice. Liver GK activity in humans and rodents is allosterically inhibited by GK regulatory protein (GKRP). To further understand the role of GKRP in GK regulation, the mouse GKRP gene was inactivated. With the knockout of the GKRP gene, there was a parallel loss of GK protein and activity in mutant mouse liver. The loss was primarily because of posttranscriptional regulation of GK, indicating a positive regulatory role for GKRP in maintaining GK levels and activity. As in rat hepatocytes, both GK and GKRP were localized in the nuclei of mouse hepatocytes cultured in low-glucose-containing medium. In the presence of fructose or high concentrations of glucose, conditions known to relieve GK inhibition by GKRP in vitro, only GK was translocated into the cytoplasm. In the GKRP-mutant hepatocytes, GK was not found in the nucleus under any tested conditions. We propose that GKRP functions as an anchor to sequester and inhibit GK in the hepatocyte nucleus, where it is protected from degradation. This ensures that glucose phosphorylation is minimal when the liver is in the fasting, glucose-producing phase. This also enables the hepatocytes to rapidly mobilize GK into the cytoplasm to phosphorylate and store or metabolize glucose after the ingestion of dietary glucose. In GKRP-mutant mice, the disruption of this regulation and the subsequent decrease in GK activity leads to altered glucose metabolism and impaired glycemic control.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Expression of human hepatic glucokinase in transgenic mice liver results in decreased glucose levels and reduced body weight.

Glucokinase is the predominant hexokinase in pancreatic beta-cells and liver parenchymal cells and functions as a critical component of the glucose-sensing apparatus in these glucose-responsive cell types. In the beta-cells, the sensing leads to insulin secretion, while the role in hepatocytes is thought to be in hepatic glucose uptake. To determine the physiological response to an increase in hepatic glucokinase expression, transgenic mice expressing the human hepatic glucokinase gene under the control of a liver-specific human apolipoprotein A-I gene enhancer were generated. Transgenic mice had twofold higher total fasting hepatic glucokinase mRNA, which resulted in a modest 20% increase in fasting glucokinase activity. These animals showed lower fasting plasma glucose, insulin, and lactate levels and improved tolerance to glucose. In addition, glucokinase transgenic animals weighed less and had lower BMI than nontransgenic animals. Thus, glucokinase transgenic animals demonstrate that a modest change in hepatic glucokinase activity enhances the metabolism of glucose.

Animals↗

PubMed1996