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Biomedical subjects

J A Clark

Publications and source records attributed to J A Clark.

165 records · Page 10Linked to original sources
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Viscoelastic behavior of tissue in leg lengthening by distraction.

The leg lengthening distraction procedure was analyzed with objectives of understanding complications which arise due to overstretching, establishing guidelines to the optimum distraction rates and the frequency of distraction, and, determining the final amount of leg lengthening. An electronic recording system was devised to provide continuous monitoring of the tractive load resulting from distraction of the leg during the elongation procedure. The mechanical behavior patterns of the involved stretched tissues domonstrate time-dependent viscoelastic effects during distraction. During a leg lenthening procedure it is desirable to establish, if possible, a regular pattern of distraction early in the process. If it is necessary in the course of treatment to reduce the distraction rate for clinical reasons, then it is preferable to keep the same number of distraction events but reduce the distraction amount. Distract at equally spaced time intervals to obtain repetitive load cycles and thereby reduce peak values of load and maintain similar stress relaxation patterns for each instantaneous load increase. The total amount of lengthening depends on the characteristics of each individual leg length discrepancy and the physical properties of each distracted tissue.

Adolescent↗
PubMedDate not supplied

Streptozotocin, an analog of N-acetylglucosamine, blocks the removal of O-GlcNAc from intracellular proteins.

Streptozotocin (STZ), an analog of N-acetylglucosamine (GlcNAc), is a specific toxin for the pancreatic beta cell. We found that treatment of rats with STZ results in an early beta-cell-specific increase in the level of intracellular protein modification by O-linked GlcNAc (O-GlcNAc). Using a model O-GlcNAc peptide based on the transcription factor Sp1, we show that treatment of cultured cells with STZ during peptide biosynthesis results in hyperglycosylation of the peptide as a result of the ability of STZ to specifically inhibit the activity of O-GlcNAc-selective N-acetyl-beta-D-glucosaminidase. Although this inhibitory activity of STZ probably can occur in all cells, we found, using in situ hybridization, that beta cells express very high levels of the mRNA encoding the enzyme responsible for cytoplasmic protein O-glycosylation, O-GlcNAc transferase (OGT). These findings suggest that the pancreatic beta cell is particularly sensitive to the toxicity of STZ because it expresses such high levels of OGT. When STZ blocks O-GlcNAc removal from intracellular proteins, the cell with the most rapid on-rate for O-GlcNAc, the beta cell, will experience the most rapid accumulation of this protein modification. Because we also show that the on-rate of O-GlcNAc is substrate driven in several cell types, we speculate that the beta cell, with its high level of OGT, may also respond to elevations of blood sugar with increased protein modification by O-GlcNAc. Thus, this proposed mechanism of STZ toxicity on the beta cell may result from an exaggeration of a heretofore unrecognized physiological response to glucose mediated through the high level of OGT in these cells.

Acetylglucosamine↗