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Biomedical subjects

Timothy Erickson

Publications and source records attributed to Timothy Erickson.

8 recordsLinked to original sources

Pbx proteins cooperate with Engrailed to pattern the midbrain-hindbrain and diencephalic-mesencephalic boundaries.

Pbx proteins are a family of TALE-class transcription factors that are well characterized as Hox co-factors acting to impart segmental identity to the hindbrain rhombomeres. However, no role for Pbx in establishing more anterior neural compartments has been demonstrated. Studies done in Drosophila show that Engrailed requires Exd (Pbx orthologue) for its biological activity. Here, we present evidence that zebrafish Pbx proteins cooperate with Engrailed to compartmentalize the midbrain by regulating the maintenance of the midbrain-hindbrain boundary (MHB) and the diencephalic-mesencephalic boundary (DMB). Embryos lacking Pbx function correctly initiate midbrain patterning, but fail to maintain eng2a, pax2a, fgf8, gbx2, and wnt1 expression at the MHB. Formation of the DMB is also defective as shown by a caudal expansion of diencephalic epha4a and pax6a expression into midbrain territory. These phenotypes are similar to the phenotype of an Engrailed loss-of-function embryo, supporting the hypothesis that Pbx and Engrailed act together on a common genetic pathway. Consistent with this model, we demonstrate that zebrafish Engrailed and Pbx interact in vitro and that this interaction is required for both the eng2a overexpression phenotype and Engrailed's role in patterning the MHB. Our data support a novel model of midbrain development in which Pbx and Engrailed proteins cooperatively pattern the mesencephalic region of the neural tube.

Animals↗

Chemically induced seizures.

Drug- and toxin-associated seizures (DTS) may result from exposure to a wide variety of agents. Most DTS can be managed with supportive care. First-line anticonvulsant therapy should include benzodiazepines, unless agents require a specific antidote. Phenytoin is generally not expected to be useful for DTS and in some instances may be harmful. In this article the authors discuss the pathophysiology of DTS, the potential differential diagnosis, and the clinical presentation. They also review selected agents that cause DTS and provide an overview of how the clinician should approach the management of patients who have DTS.

Antidotes↗

Coca tea consumption causes positive urine cocaine assay.

BACKGROUND: Coca tea, derived from the same plant that is used to synthesize cocaine, is commonly consumed in South America and easily obtained in the United States. OBJECTIVES: To determine whether consumption of coca tea would result in a positive urine toxicology screen for cocaine metabolites. METHODS: Five healthy adult volunteers consumed coca tea and underwent serial quantitative urine testing for cocaine metabolites by fluorescence polarization immunoassay. The cutoff for a positive assay was chosen at 300 ng/ml, the National Institute on Drug Abuse standard. RESULTS: Each participant's urine cocaine assay was positive (level exceeding 300 ng/ml) by 2 h after ingestion. Three out of five participants' samples remained positive at 36 h. Mean urine benzoylecgonine concentrations in all postconsumption samples was 1777 ng/ml (95% confidence interval: 1060-2495). CONCLUSIONS: Coca tea ingestion resulted in a positive urine assay for cocaine metabolite. Healthcare professionals should consider a history of coca tea ingestion when interpreting urine toxicology results.

Adult↗

Drug- and toxin-associated seizures.

Drug- and toxin-associated seizures may result from exposure to a wide variety of agents. Obtaining a comprehensive history behind the exposure is generally more helpful than diagnostic testing. Most DTS may be managed with supportive care, including benzodiazepines, except in the case of agents that require a specific intervention or antidote.

Drug-Related Side Effects and Adverse Reactions↗

Coordinated changes in classes of ribosomal protein gene expression is associated with light-induced retinal degeneration.

PURPOSE: To identify genes with altered expression levels in the degenerating retina in a light-induced retinal degeneration (LIRD) model. METHODS: Adult Sprague-Dawley rats were exposed to intense green light for 4 hours. After this treatment, the retinas were excised, RNA was extracted, and a cDNA library was prepared. The cDNA library was differentially cross-screened with probes representing 0-hour and 4-hour light-exposed rat retina. Transcripts with altered expression levels were sequenced and expression was confirmed by Northern blot analysis. Gene-specific primers were designed and used to examine the expression levels of other genes involved in protein synthesis. Promoter sequences of the ribosomal-binding protein (Rbp) genes were analyzed for transcription-binding sites. RESULTS: Of the 10,000 clones that were initially screened, 41 exhibited altered expression levels. Six of these corresponded to five known Rbp genes. Six additional Rbp genes were also examined. In total, 9 of 11 Rbp genes exhibited an increase in expression levels in response to a 4-hour light exposure. In contrast, the transcript levels of elongation factor 1alpha1 and 18S rRNA did not increase. The most abundant transcription factor-binding sites conserved in the promoter regions of all Rbp genes examined in this study include AP-1, Oct-1, V-myb, USF, Pax-4, and the FOX family of transcription factors. CONCLUSIONS: The results indicate that light-induced retinal degeneration (LIRD) is associated with increased expression of specific Rbp genes. These Rbp genes may be involved in mediating visual cell loss in LIRD through a translational or an extraribosomal mechanism.

Animals↗

Variation in patient management based on ECG interpretation by emergency medicine and internal medicine residents.

This study was performed to determine the impact of electrocardiogram (ECG) interpretation on urgent patient care decisions by internal medicine (IM) and emergency medicine (EM) resident physicians. Six clinical scenarios and ECGs were given to 31 IM residents and 31 EM residents at a university medical center. Based on the ECG interpretation, the residents were asked to select the best patient management from a list of choices. IM and EM residents were equally likely to choose the correct management for complete heart block (90% IM v 97% EM, P = NS), and pulseless ventricular tachycardia (VT) (94% IM v 97% EM, P = NS). IM residents were less likely to choose the correct management for acute posterior wall myocardial infarction (MI) (26% IM v 74% EM, P <.0001) and unstable supraventricular tachycardia (SVT) (87% IM v 100% EM, P <.05). Residents in both programs were equally likely to misinterpret left ventricular hypertrophy (LVH) (23% IM and 16% EM, P = NS) and benign early repolarization (BER) (48% IM and 52% EM, P = NS) as acute myocardial ischemia when presented with a clinical history not suggestive of cardiac ischemia. IM and EM residents were equally likely to choose the correct management for complete heart block and pulseless VT. Compared with EM residents, IM residents were less likely to choose the correct management of posterior wall MI and unstable SVT. Both IM and EM residents were prone to misinterpreting LVH and BER as acute myocardial ischemia. Resident education in both specialties should focus on ECG interpretation skills to improve patient management decisions.

Aged↗