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In JoVE (1)
Other Publications (6)
Articles by Leslie T.C. Worrell in JoVE
JoVE Neuroscience
In vitro Electroporation of the Lower Rhombic Lip of Midgestation Mouse Embryos
Biology Department, University of Illinois at Springfield
This study describes the development of an in vitro electroporation technique that allows for the manipulation of gene expression in the lower rhombic lip of midgestation embryos.
Other articles by Leslie T.C. Worrell on PubMed
Electromyographic Reliability and Analysis of Selected Lower Extremity Muscles During Lateral Step-up Conditions
To determine 1) the electromyographic (EMG) reliability within and between testing sessions; 2) the effect of sex on the EMG activity of the vastus medialis oblique (VMO), vastus lateralis (VL), hamstring (HS), and gluteus maximus (GM) and VMO:VL ratios during maximal voluntary isometric contraction (MVIC) and lateral step-up (LSU) conditions; and 3) the muscle recruitment and VMO:VL ratios during MVIC and LSU conditions.
Tenofovir Disoproxil Fumarate and an Optimized Background Regimen of Antiretroviral Agents As Salvage Therapy for Pediatric HIV Infection
Highly active antiretroviral therapy has altered the course of HIV infection among children, but new antiretroviral agents are needed for treatment-experienced children with drug-resistant virus. Tenofovir disoproxil fumarate (DF) is a promising agent for use in pediatric salvage therapy, because of its tolerability, efficacy, and resistance profile. We designed this study to provide preliminary pediatric safety and dosing information on tenofovir DF, while also providing potentially efficacious salvage therapy for heavily treatment-experienced, HIV-infected children.
Tenofovir Disoproxil Fumarate and an Optimized Background Regimen of Antiretroviral Agents As Salvage Therapy: Impact on Bone Mineral Density in HIV-infected Children
Tenofovir disoproxil fumarate, a nucleotide analog HIV reverse transcriptase inhibitor with demonstrated activity against nucleoside-resistant HIV, is approved for use in adults but not children. Metabolic bone abnormalities have been seen in young animals given high-dose tenofovir and HIV-infected adults that were treated with oral tenofovir disoproxil fumarate. However, tenofovir disoproxil fumarate is being used in children despite a lack of bone safety data. We hypothesized that, given the higher rate of bone turnover that is associated with normal skeletal growth, the potential for TDF-related bone toxicity may be greater in children than in adults.
Identification of Early Interstitial Lung Disease in an Individual with Genetic Variations in ABCA3 and SFTPC
A man with usual interstitial pneumonia (age of onset 58 years) was previously found to have an Ile73Thr (I73T) surfactant protein C (SFTPC) mutation. Genomic DNA from the individual and two daughters (aged 39 and 43 years) was sequenced for the I73T mutation and variations in ATP-binding cassette A3 (ABCA3). All three had the I73T SFTPC mutation. The father and one daughter (aged 39 years) also had a transversion encoding an Asp123Asn (D123N) substitution in ABCA3. The daughters were evaluated by pulmonary function testing and high-resolution CT (HRCT). Neither daughter had evidence of disease, except for focal subpleural septal thickening on HRCT scan in one daughter (aged 39 years). This daughter underwent bronchoscopy with transbronchial biopsies revealing interstitial fibrotic remodeling. These findings demonstrate that subclinical fibrotic changes may be present in family members of patients with SFTPC mutation-associated interstitial lung disease and suggest that ABCA3 variants could affect disease pathogenesis.
Update in Neonatal Diabetes
Here we give context to new data on neonatal diabetes mellitus, a rare group of insulin-requiring monogenic forms of diabetes presenting at birth or shortly thereafter. Genetic studies are critical in the diagnosis and treatment of these patients. The most common causes of neonatal diabetes are activating mutations in the two protein subunits of the ATP-sensitive potassium channel. These are responsible for about half of all cases of permanent neonatal diabetes and some cases of transient neonatal diabetes. Identification of these mutations allows patients treated with insulin to be transferred to sulfonylureas, but associated conditions and other causes must be considered.
2,4-Diaminopyrimidine Inhibitors of C-Met Kinase Bearing Benzoxazepine Anilines
Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which kinase selectivity was modulated by substituents appended on the C4-aminobenzamide ring and the nature of the C2-aminoaryl ring. Further lead optimization of the C2-aminoaryl group led to benzoxazepine analogs whose pharmaceutical properties were modulated by the nature of the substituent on the benzoxazepine nitrogen. Tumor stasis (with partial regressions) were observed when an orally bioavailable analog was evaluated in a GTL-16 tumor xenograft mouse model. Subsequent PK/PD studies suggested that a metabolite contributed to the overall in vivo response.
