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Biomedical subjects

Eric J Buenz

Publications and source records attributed to Eric J Buenz.

9 recordsLinked to original sources

A high-throughput 3-parameter flow cytometry-based cell death assay.

Apoptosis plays a role in many disease states, and the evaluation of novel therapeutics that alters the apoptotic cascade is an area of intense investigation. However, many generally available methods to evaluate cell death are either time consuming, imprecise, or both. We report a system that permits simultaneous evaluation of three apoptotic markers (cell membrane integrity, mitochondrial membrane potential, and cell cycle progression) with minimal technical manipulation. This system is particularly well-suited for toxicologic evaluation of novel compounds and profiling of new apoptosis-inducing agents.

Apoptosis↗

Disrupted spatial memory is a consequence of picornavirus infection.

Picornaviruses are a socioeconomically important family of viruses that includes the rhinoviruses and enteroviruses. Many of these viruses, including the "common cold" Coxsackie virus A21, maintain neurovirulent potential and may induce hippocampal injury. The behavioral implications of this injury have not been adequately explored. Using C57BL/6J mice infected with Theiler's murine encephalomyelitis virus, we examined the formation of spatial memories using the Morris water maze test. Virus-infected mice had greater search error compared to sham-infected animals during the location of a hidden platform and were unable to discriminate the location of the training quadrant during the final probe trial. Furthermore, sham-infected mice were place responders whereas virus-infected mice were cue responders, indicating a lack of spatial memory formation in infected animals. Importantly, the degree of memory impairment was correlated to the extent of hippocampal injury. This suggests that picornavirus infection of the human CNS may also result in at least some degree of neurologic deficit. An important implication of such subclinical virus-induced neurologic deficit is that the injury may accumulate over the lifetime of the individual, eventually leading to the manifestation of clinical cognitive or memory deficits.

Animals↗

Mitochondrial involvement in Atuna racemosa induced toxicity.

Our group has developed a system to extract information regarding potential novel pharmaceuticals from historic herbal texts. We have shown that one of the plants identified through this technique has the purported antibacterial properties suggested by the text. Here, the toxicity of this antibacterial extract was examined. Using a Jurkat cell model, a therapeutic window between the minimal inhibitory concentration for Gram-positive bacteria and the dose-dependent toxicity of the Atuna racemosa extract was established. Using cells with a mutated caspase 8, it was shown that the toxicity does not involve caspase 8. However, by transmission electron microscopy and a potentiometric dye, the toxicity was shown to involve the mitochondria. This toxicity also resulted in DNA cleavage and activation of caspase 3. This work suggests that the extract, originally reported as an antimicrobial therapeutic in a 400-year-old Dutch herbal text, may maintain a therapeutic window as an antibiotic. Furthermore, this work shows toxicity would occur in a mitochondrial dependent fashion.

Anti-Bacterial Agents↗

Hepatocytes detoxify Atuna racemosa extract.

A number of traditional medicine plants are hepatotoxic. Thus, while the traditional uses of Atuna racemosa suggest little indication for toxicity, it is nonetheless important to examine the potential for this extract to target the liver. Using Jurkat T cells and HepG2 hepatocytes as a model, the potential hepatotoxicity of this extract was evaluated. The results of a conditioned media experiment suggest that A. racemosa extract would likely be detoxified by the liver. These results provide the necessary background to initiate an in vivo toxicology investigation.

Cell Cycle↗

Picornaviruses and cell death.

Members of the picornavirus family, including poliovirus and foot-and-mouth disease virus, are widespread pathogens of humans and domestic animals. Recent global developments in the resurgence of poliovirus infection and in the control of foot-and-mouth disease infection highlight the problems caused by the ability of picornaviruses to alter the apoptotic machinery of host cells and establish persistent infections. Despite the medical, economic and social impact of this family of viruses, little information exists that integrates the mechanisms of cell death and damage induced by related family members. Fortunately, examination of the reported roles and functions of individual viral proteins from multiple picornaviruses makes it possible to surmise canonical functions for these proteins. This review analyzes the canonical function of picornavirus proteins involved in the alteration of apoptotic homeostasis in infected host cells.

Animals↗

Impact of mitochondrial regulation of apoptosis on the pathogenesis and treatment of HIV-1-induced immunodeficiency.

HIV-1 infection causes the depletion of CD4 T cells, which results in AIDS. There are numerous potential mechanisms by which this cell death can occur, and a majority of the molecular mechanisms involve the mitochondria. Furthermore, current HIV therapies also have an impact on mitochondrial stability. The alteration in apoptotic homeostasis induced by HIV, HIV proteins, the host response to HIV infection and/or HIV therapies either promote apoptosis or inhibit apoptotic signals depending on the cellular context. Latent HIV reservoirs prevent the eradication of the virus because these cells are resistant to apoptosis: a change potentially induced at the level of the mitochondria. Many of the novel treatment strategies aimed at eradicating the virus involve alterations of mitochondrial regulation of apoptosis.

Journal Article↗

Techniques: Bioprospecting historical herbal texts by hunting for new leads in old tomes.

Ethnobotany has led to the identification of novel pharmacological agents but many challenges to using ethnobotany as a research tool remain. In particular, the loss of traditional knowledge together with the advent of high-throughput screening has made ethnobotanical techniques laborious and potentially unnecessary. However, historical herbal texts provide a preexisting resource that documents the traditional uses of various species as medicines. As generational losses of traditional knowledge accrue, these herbal texts become increasingly valuable. The methodology for extracting useful information contained within these resources had been cumbersome and consuming. However, the application of new bioinformatics data-mining systems to herbal texts holds great promise for identifying novel pharmacotherapeutic leads for bioactive compounds.

Ethnobotany↗