Contact areas in the thumb carpometacarpal joint

The thumb carpometacarpal joint is a common site of osteoarthritis. It has been hypothesized that peaks of localized stress on the dorsoradial or volar-ulnar regions, or both, of the articular surfaces of the trapezium and metacarpal lead to erosion of cartilage and may be responsible for the progression of the disease. The objective of this study was to determine the contact areas in this joint under the functional position of lateral (key) pinch and in the extremes of range of motion of the joint. These contact areas were assessed relative to the observed sites of cartilage thinning. Eight hands from cadavers of women and five from cadavers of men were tested in vitro with the thumb under a 25 N load in the lateral pinch position, and under small muscle loads (0-5 N) with the thumb in flexion, extension, abduction, adduction, and neutral positions. Contact areas of articular surfaces of the thumb carpometacarpal joint were determined for these positions using a stereophotogrammetric technique. The lateral pinch position produced contact areas predominantly on the central, volar, and volar-ulnar regions of the trapezium and the metacarpal. In three specimens, contact areas were distinctly separated between the dorsoradial and volar-ulnar regions, and in one specimen, from a man, contact occurred exclusively on the dorsoradial region of the trapezium. Using stereophotogrammetry, maps of cartilage thickness also were determined for a subset of nine specimens. The volar-ulnar, ulnar, and dorsoradial regions of the trapezium were the most common sites of thin cartilage, and these may be sites of cartilage wear.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevation of serum cholesterol levels in mice by the antioxidant butylated hydroxyanisole

The food antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are structurally related to the hypocholesterolemic drug probucol. The purpose of this study was to determine if BHA can lower serum cholesterol levels as is observed with probucol. Treatment of mice with 0.75% BHA in their feed for 10 days resulted in a significant (P < or = 0.01) elevation of serum cholesterol levels. This effect contrasts with the cholesterol-lowering effect of probucol. Further, the degree of cholesterol elevation was comparable to that observed in mice administered 3% cholesterol in their feed for 7 days. The enzyme acyl CoA:cholesterol acyltransferase (ACAT) was decreased significantly (P < or = 0.01) in liver microsomes from BHA-treated mice. In contrast, hepatic microsomal ACAT activity was increased significantly (P < or = 0.01) in cholesterol-fed mice. These results suggested that the increased serum cholesterol observed in BHA-treated mice was not accompanied by an increase in hepatic cholesterol levels. Indeed, hepatic microsomal cholesterol levels were reduced in BHA-treated mice, but were increased significantly (P < or = 0.01) in cholesterol-fed mice. These results demonstrate that the common food additive BHA elevates serum cholesterol levels by a mechanism that apparently involves the decreased uptake of cholesterol by the liver.     

The positive-acting sulfur regulatory protein CYS3 of Neurospora crassa: nuclear localization, autogenous control, and regions required for transcriptional activation

The positive-acting global sulfur regulatory protein, CYS3, of Neurospora crassa turns on the expression of a family of unlinked structural genes that encode enzymes of sulfur catabolism. CYS3 contains a leucine zipper and an adjacent basic region (b-zip), which together constitute a bipartite sequence-specific DNA-binding domain. Specific anti-CYS3 antibodies detected a protein of the expected size in nuclear extracts of wild-type Neurospora under conditions in which the sulfur circuit is activated. The CYS3 protein was not observed in cys-3 mutants. Nuclear extracts of wild type, but not cys-3 mutants, also showed specific DNA-binding activity identical to that obtained with a CYS3 protein expressed in Escherichia coli. A truncated CYS3 protein that contains primarily the b-zip domain binds to DNA with high specificity and affinity in vitro, yet fails to activate gene expression in vivo, and instead inhibits the function of the wild-type CYS3 protein. Amino-terminal, carboxyterminal, and internal deletions as well as alanine scanning mutagenesis were employed to identify regions of the CYS3 protein that are required for its trans-activation function. Regions of CYS3 carboxy terminal to the b-zip motif are not completely essential for function although loss of an alanine-rich region results in decreased activity. All deletions amino terminal to the b-zip motif led to a complete loss of CYS3 function. Alanine scanning mutagenesis demonstrated that an unusual prolinerich domain of CYS3 appears to be very important for function and is presumed to constitute an activation domain. It is concluded that CYS3 displays nuclear localization and positive autogenous control in Neurospora and functions as a trans-acting DNA-binding protein.