Biomedical subjects

C Burt

Publications and source records attributed to C Burt.

15 recordsLinked to original sources

PubMed2001

Shoulder-pad sign of amyloidosis: structure of an Ig kappa III protein.

While amyloid infiltration of articular structures is rare, the 'shoulder-pad' sign resulting from periarticular soft tissue amyloid deposition is essentially pathognomonic for immunogloblin (Ig) (AL) amyloidosis. We report the characterization of an amyloid protein (GRA) which produced articular amyloid deposits and the shoulder-pad sign. Amyloid fibrils were isolated from soft tissue shoulder mass of a patient with systemic AL amyloidosis. The fibrils were solubilized in guanidine HCl and proteins separated by Sepharose chromatography. Amino acid sequence of fractionated protein was determined after tryptic digestion. Sequence analysis of the major amyloid protein yielded a kappa III Ig light chain structure. The entire variable region (VL) plus the constant region (CL) to residue 207 was identified; but lesser amounts of CL than VL were present. A number of amino acid residues previously not observed in kappa III VL proteins, plus a two amino acid insert (95A, 95B), were identified. Kappa III VL amyloid proteins are rare and may show an increased predilection for soft tissue deposition. While several unique amino acid residues that were identified in protein GRA may contribute to soft tissue amyloid deposition, no definite pattern is obvious from comparison with other reported kappa III amyloid proteins.

Aged↗

PubMed2001

Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines.

Patients with glucocorticoid excess develop central obesity, yet in simple obesity, circulating glucocorticoid levels are normal. We have suggested that the increased activity and expression of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) generating active cortisol from cortisone within adipose tissue may be crucial in the pathogenesis of obesity. In this study primary cultures of human hepatocytes and adipose stromal cells (ASC) were used as in vitro models to investigate the tissue-specific regulation of 11betaHSD1 expression and activity. Treatment with tumor necrosis factor-alpha (TNFalpha) caused a dose-dependent increase in 11betaHSD1 activity in primary cultures of both sc [1743.1 +/- 1015.4% (TNFalpha, 10 ng/ml); P < 0.05 vs. control (100%)] and omental [375.8 +/- 57.0% (TNFalpha, 10 ng/ml); P < 0.01 vs. control (100%)] ASC, but had no effect on activity in human hepatocytes [90.2 +/- 2.8% (TNFalpha, 10 ng/ml); P = NS vs. control (100%)]. Insulin-like growth factor I (IGF-I) caused a dose-dependent inhibition of 11betaHSD1 activity in sc [49.7 +/- 15.0% (IGF-I, 100 ng/ml]; P < 0.05 vs. control (100%)] and omental [71.6 +/- 7.5 (IGF-I, 100 ng/ml); P < 0.01 vs. control (100%)] stromal cells, but not in human hepatocytes [101.8 +/- 15.7% (IGF-I, 100 ng/ml); P = NS vs. control (100%)]. Leptin treatment did not alter 11betaHSD1 activity in human hepatocytes, but increased activity in omental ASC [135.8 +/- 14.1% (leptin, 100 ng/ml); P = 0.08 vs. control (100%)]. Treatment with interleukin-1beta induced 11betaHSD1 activity and expression in sc and omental ASC in a time- and dose-dependent manner. 15-Deoxy-12,14-PGJ2, the putative endogenous ligand of the orphan nuclear receptor peroxisome proliferator-gamma, significantly increased 11betaHSD1 activity in omental cells [179.7 +/- 29.6% (1 microM); P < 0.05 vs. control (100%)] and sc [185.3 +/- 12.6% (1 microM); P < 0.01 vs. control (100%)] ASC, and it is possible that expression of this ligand may ensure continued cortisol generation to permit adipocyte differentiation. Protease inhibitors used in the treatment of human immunodeficiency virus infection are known to cause a lipodystrophic syndrome and central obesity, but saquinavir, indinavir, and neflinavir caused a dose-dependent inhibition of 11betaHSD1 activity in primary cultures of human omental ASC. 11betaHSD1 expression is increased in human adipose tissue by TNFalpha, interleukin-1beta, leptin, and orphan nuclear receptor peroxisome proliferator-gamma agonists, but is inhibited by IGF-I. This autocrine and/or paracrine regulation is tissue specific and explains recent clinical data and animal studies evaluating cortisol metabolism in obesity. Tissue-specific 11betaHSD1 regulation offers the potential for selective enzyme inhibition within adipose tissue as a novel therapy for visceral obesity.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1993

Optoelectronic evaluation of trunk deformity in scoliosis.

In this study, truncal deformity in patients with scoliosis was evaluated by circumferential scanning using an optoelectronic device (Optronic Torsograph, Anima Corp., Tokyo, Japan). This device generates cross-sectional skin surface topography at 10 axial levels to provide a three-dimensional representation of truncal shape. Ninety-three patients with suspected idiopathic scoliosis were evaluated with conventional Cobb measurements, and their parameters were computed using the device's measurements. The geometric cross-sectional indexes correlated poorly with the Cobb angle and were highly variable during repeated measurements. The optoelectronic device's angle, a measure of centroid curvature, correlated highly with the Cobb angle for primary spinal curves. The highest correlation was observed in thoracolumbar curves. This optoelectronic device has clinical relevance as a method for further scoliosis screening and monitoring the progression of spinal curvature in a patient.

Adolescent↗

PubMed1991

A prototype bioreductive DNA groove binding ligand.

Molecular mechanics calculations have been used to evaluate the potential bioreductive behaviour of several DNA minor groove binding ligands containing quinone/hydroquinone redox systems. The proposed structures are analogues of the Hoechst 33258 molecule with modifications of the benzimidazole rings. Binding energies of simple analogues indicate the reduced forms bind more strongly to the DNA minor groove. N-methylation of the imidazole ring(s) produces structures which can form extended quinone methides. These also show stronger binding in the reduced form and it is speculated that such structures might provide a basis for the design of groove binding ligands which will act as bioreductive alkylating agents.

Base Sequence↗

PubMed1990