PubMed Health⌕ Search

Biomedical subjects

James Baker

Publications and source records attributed to James Baker.

10 recordsLinked to original sources
PubMed2006

Pharmacological characterization of novel water-soluble cannabinoids.

Presently, there are numerous structural classes of cannabinoid receptor agonists, all of which require solubilization for experimental purposes. One strategy for solubilizing water-insoluble tetrahydrocannabinols is conversion of the phenolic hydroxyl to a morpholinobutyryloxy substituent. The hydrochloride salts of these analogs are water-soluble and active in vivo when administered in saline. The present investigation demonstrated that hydrochloride salts of numerous substituted butyryloxy esters are water-soluble and highly potent. The substitutions include piperidine, piperazine, and alkyl-substituted amino moieties. It was also discovered that incorporation of a nitrogenous moiety in the alkyl side chain increased the pharmacological potency of tetrahydrocannabinol. For example, an analog containing a pyrazole in the side chain (O-2545) was found to have high affinity and efficacy at cannabinoid 1 (CB(1)) and CB(2) receptors, and when dissolved in saline, it was highly efficacious when administered either intravenously or intracerebroventricularly to mice. A series of carboxamido and carboxylic acid amide analogs exhibited high pharmacological potency, but their hydrochloride salts were not water-soluble. On the other hand, incorporation of imidazoles into the terminus of the side chain led to water-soluble hydrochloride salts that were highly potent when administered in saline to laboratory animals. It is now possible to conduct cannabinoid research with agonists that are water-soluble and thus obviating the need of solubilizing agents.

Animals↗
PubMed2005

Atomic force microscopy study of early morphological changes during apoptosis.

Apoptosis is defined by a distinct set of morphological changes observed during cell death including loss of focal adhesions, the formation of cell membrane buds or blebs, and a decrease in total cell volume. Recent studies suggest that these dramatic morphological changes, particularly apoptotic volume decrease (AVD), are an early prerequisite to apoptosis and precede key biochemical time-points. Here we use atomic force microscopy to observe early stage AVD of KB cells undergoing staurosporine-induced apoptosis. After a 3-h exposure to 1 microM staurosporine, a 32% decrease in total cell height and a 50% loss of total cell volume is observed accompanied by only a 15% change in cell diameter. The observed AVD precedes key biochemical hallmarks of apoptosis such as loss of mitochondrial membrane potential, phosphatidyl serine translocation, nuclear fragmentation, and measurable caspase-3 activity. This suggests that morphological volume changes occur very early in the induction of apoptosis.

Apoptosis↗
PubMed2004

The Drosophila pericentrin-like protein is essential for cilia/flagella function, but appears to be dispensable for mitosis.

Centrosomes consist of a pair of centrioles surrounded by an amorphous pericentriolar material (PCM). Proteins that contain a Pericentrin/AKAP450 centrosomal targeting (PACT) domain have been implicated in recruiting several proteins to the PCM. We show that the only PACT domain protein in Drosophila (the Drosophila pericentrin-like protein [D-PLP]) is associated with both the centrioles and the PCM, and is essential for the efficient centrosomal recruitment of all six PCM components that we tested. Surprisingly, however, all six PCM components are eventually recruited to centrosomes during mitosis in d-plp mutant cells, and mitosis is not dramatically perturbed. Although viable, d-plp mutant flies are severely uncoordinated, a phenotype usually associated with defects in mechanosensory neuron function. We show that the sensory cilia of these neurons are malformed and the neurons are nonfunctional in d-plp mutants. Moreover, the flagella in mutant sperm are nonmotile. Thus, D-PLP is essential for the formation of functional cilia and flagella in flies.

Animals↗
PubMed2002

Operation safe crossing: using science within a community intervention.

AIMS: To evaluate a large drunk-driving enforcement program at the US/Mexican border to reduce the number of youths crossing the border to drink in Tijuana. This paper also describes the research data used to develop and manage the program. Data from a border breath-test survey were used to dramatize the problem and gain public support for action. The data were also used to help design the enforcement effort and measure progress in reducing the cross-border drinking problem. DESIGN: The number of news events generated around the occurrence of special enforcement efforts were used to measure project activity and to predict changes in the numbers of youths crossing into Mexico, their returning BACs and reductions in alcohol-related crashes during a 3-year period. SETTING: An urban county on the Mexican border. PARTICIPANTS: Underage youths aged 18-20 years and young adults aged 21-30 years residing in San Diego County. MEASUREMENTS: Immigration and Naturalization Services provided population counts of the number of individuals crossing each weekend night from Tijuana into the United States through the San Ysidro border facility. Breath-test surveys of a random sample of these returning crossers provided data on the number of US residents visiting bars and nightclubs in Tijuana and on alcohol consumption at Tijuana bars and nightclubs. Night-time had-been-drinking crash data involving young drivers in several California counties served as an outcome measure of public health and safety. FINDINGS: Analysis of data involving more than 2 million pedestrians returning from Tijuana indicated that the Operation Safe Crossing program reduced the number of late-night crossers by 31.6%. CONCLUSIONS: Effective use of data through media advocacy programs to support an enforcement effort can reduce alcohol-related crashes.

Adolescent↗