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Biomedical subjects

N Somia

Publications and source records attributed to N Somia.

6 recordsLinked to original sources
PubMed2001

Regulation of antioxidant metabolism by translation initiation factor 2alpha.

Oxidative stress and highly specific decreases in glutathione (GSH) are associated with nerve cell death in Parkinson's disease. Using an experimental nerve cell model for oxidative stress and an expression cloning strategy, a gene involved in oxidative stress-induced programmed cell death was identified which both mediates the cell death program and regulates GSH levels. Two stress-resistant clones were isolated which contain antisense gene fragments of the translation initiation factor (eIF)2alpha and express a low amount of eIF2alpha. Sensitivity is restored when the clones are transfected with full-length eIF2alpha; transfection of wild-type cells with the truncated eIF2alpha gene confers resistance. The phosphorylation of eIF2alpha also results in resistance to oxidative stress. In wild-type cells, oxidative stress results in rapid GSH depletion, a large increase in peroxide levels, and an influx of Ca(2+). In contrast, the resistant clones maintain high GSH levels and show no elevation in peroxides or Ca(2+) when stressed, and the GSH synthetic enzyme gamma-glutamyl cysteine synthetase (gammaGCS) is elevated. The change in gammaGCS is regulated by a translational mechanism. Therefore, eIF2alpha is a critical regulatory factor in the response of nerve cells to oxidative stress and in the control of the major intracellular antioxidant, GSH, and may play a central role in the many neurodegenerative diseases associated with oxidative stress.

Antioxidants↗
PubMed2000

Gene therapy: trials and tribulations.

The art and science of gene therapy has received much attention of late. The tragic death of 18-year-old Jesse Gelsinger, a volunteer in a Phase I clinical trial, has overshadowed the successful treatment of three children suffering from a rare but fatal immunological disease. In the light of the success and tragedy, it is timely to consider the challenges faced by gene therapy--a novel form of molecular medicine that may be poised to have an important impact on human health in the new millennium.

Adolescent↗
PubMed1999

Distal Interphalangeal Joint Arthrodesis Using Intramedullary and Interosseous Fixation.

Multiple fixation techniques have been developed for distal interphalangeal (DIP) joint arthrodesis. Delayed and nonunion rates varying from 0% to 20% have been reported. The senior author has refined a technique for DIP joint arthrodesis by using an intramedullary Kirschner wire and an interosseous wire for fusion of the DIP joint and interphalangeal (IP) joint of the thumb. In 24 joint arthrodeses in 19 patients, the nonunion rate was 4%, and the minor complication rate was 12%. The advantages of this technique include the absence of protruding hardware that would necessitate removal; consistency in achieving osteosynthesis, with a low nonunion rate; and technical simplicity.

Journal Article↗
PubMed1998

The initiation and sequence of digital joint motion. A three-dimensional motion analysis.

We studied the initiation and sequence of digital joint motion during unrestricted flexion and extension using a 3-D motion analysis of all fingers moving simultaneously. Our results showed that motion started in a single joint in 83%, of flexion and 80%, of extension cycles. The DIP joint initiated flexion and extension in the index, middle, and ring fingers, but in the little finger, flexion started in the PIP joint, and extension in the MP joint. The two most frequent sequences of joint movement during flexion of the three radial fingers were DIP-PIP-MP and PIP-DIP-MP. The two most frequent sequences during extension of the three radial fingers were DIP-MP-PIP followed by DIP-MP/PIP. In the little finger, however, the most frequent sequences during flexion were PIP-DIP-MP followed by DIP-PIP-MP and during extension, DIP-MP/PIP followed by PIP/DIP-MP.

Adult↗
PubMed1992

Cloning and sequence of a beta-tubulin cDNA from Pneumocystis carinii: possible implications for drug therapy.

This work describes the isolation and characterization of a full-length cDNA clone encoding beta-tubulin from the pathogen Pneumocystis carinii. P. carinii contains a single gene encoding beta-tubulin. The complete sequence of this cDNA has been determined and its inferred amino acid sequence compared with the beta-tubulins from other organisms. This analysis augments the data indicating that P. carinii should be classified as a fungal organism. Further comparisons between the P. carinii beta-tubulin and those of fungal beta-tubulins resistant to benomyl, a beta-tubulin-binding drug, indicate a difference which may be exploited in the development of a new drug therapy for P. carinii pneumonitis. These results suggest that, theoretically, a drug presently administered for treatment of nematode worm infections may be an effective agent against P. carinii, without being toxic to the mammalian host. This possibility is currently being investigated.

Amino Acid Sequence↗