Subclinical slipped capital femoral epiphysis. Relationship to osteoarthrosis of the hip

We examined the femora of 2665 adult human skeletons from an osteological collection to determine the prevalence of post-slip morphology termed femoral head-tilt deformity by Murray and pistol-grip deformity by Stulberg et al. The hypothesis was that primary osteoarthrosis of the hip is a secondary manifestation of a subclinical developmental disorder of the hip. The prevalence of post-slip morphology was 8 per cent (215 of 2665 skeletons). Severe osteoarthrosis was more prevalent in association with post-slip morphology (116 [38 per cent] of 306 hips) than in the matched controls (seventy-nine [26 per cent] of 306 hips) (p < 0.005). In the skeletons that had unilateral post-slip morphology, severe osteoarthrosis was more prevalent in the involved hips (thirty-one [37 per cent] of eighty-three) than in the contralateral, normal hips (eighteen [22 per cent] of eighty-three) (p < 0.05). Post-slip morphology, which was unrelated to age, was found to be a major risk factor for the development of high-grade osteoarthrosis. We noted evidence of high-grade osteoarthrosis in sixty-three (68 percent) of the ninety-three hips with minimum post-slip morphology in skeletons from individuals who had been fifty-six years old or more at the time of death compared with forty-five (48 percent) of the ninety-three control hips. This difference was significant (p < 0.025) [corrected]. The osteoarthrosis in the hips with post-slip morphology was distinctly characterized by anterior flattening of the acetabulum, cystic degeneration in the anterior metaphyseal-epiphyseal region, and progression to global osteoarthrosis of the hip.     

Exogenous non-crosslinked collagen enhances granulation tissue formation in dermal excision wounds in guinea pigs

Based on previous observations indicating a role for collagen peptides in eliciting a positive feedback for collagen biosynthesis, this study was initiated to elucidate the effect of non-crosslinked collagen on granulation tissue formation in dermal excision wounds. The wounds were treated with either non-crosslinked or crosslinked native collagen, or left untreated as controls. Granulation tissue was analyzed for collagen type I mRNA, for levels of interstitial collagen and for the number of blood vessels. The results indicated significant increases in procollagen type I mRNA, in interstitial collagen, in the number of blood vessels and in epithelial advance in the non-crosslinked collagen-treated wounds relative to the untreated controls. It is assumed that the presence of non-crosslinked collagen in a healing wound enhances both procollagen type I biosynthesis and the repair process of dermal wounds, due to the more readily released collagen peptides derived from this exogenous collagen dressing.     

Intergenerational transfer of psychosocial risk in women with childhood histories of aggression, withdrawal, or aggression and withdrawal

Intergenerational transfer of risk between mothers and children, based on mothers' childhood aggression and social withdrawal, was examined in an inner-city sample. Each of the 3 studies reported involved a subset of the 909 female participants in the Concordia Longitudinal Risk Project, initiated when the participants were of school age. Using medical records, Study 1 (n = 853) focused on prediction of teen motherhood, delivery complications during childbirth, multiparity, and close spacing of births. Study 2 (n = 428) examined pathways to school dropout and teen parenthood. Study 3 (n = 89) involved prediction of observed parent and child behavior from mothers' childhood characteristics. Mothers' childhood aggression was consistently predictive of negative outcomes in each area of intergenerational risk, especially when combined with social withdrawal and low levels of academic achievement. Education was protective: Mothers' years of schooling predicted positive outcomes.     

An unusual route to thermostability disclosed by the comparison of Thermus thermophilus and Escherichia coli inorganic pyrophosphatases

The structures of Escherichia coli soluble inorganic pyrophosphatase (E-PPase) and Thermus thermophilus soluble inorganic pyrophosphatase (T-PPase) have been compared to find the basis for the superior thermostability of T-PPase. Both enzymes are D3 hexamers and crystallize in the same space group with very similar cell dimensions. Two rather small changes occur in the T-PPase monomer: a systematic removal of Ser residues and insertion of Arg residues, but only in the C-terminal part of the protein, and more long-range ion pairs from the C-terminal helix to the rest of the molecule. Apart from the first five residues, the three-dimensional structures of E-PPase and T-PPase monomers are very similar. The one striking difference, however, is in the oligomeric interactions. In comparison with an E-PPase monomer, each T-PPase monomer is skewed by about 1 A in the xy plane, is 0.3 A closer to the center of the hexamer in the z direction, and is rotated by approximately 7 degrees about its center of gravity. Consequently, there are a number of additional hydrogen bond and ionic interactions, many of which form an interlocking network that covers all of the oligomeric surfaces. The change can also be seen in local distortions of three small loops involved in the oligomeric interfaces. The complex rigid-body motion has the effect that the hexamer is more tightly packed in T-PPase: the amount of surface area buried upon oligomerization increases by 16%. The change is sufficiently large to account for all of the increased thermostability of T-PPase over E-PPase and further supports the idea that bacterial PPases, most active as hexamers or tetramers, achieve a large measure of their stabilization through oligomerization. Rigid-body motions of entire monomers to produce tighter oligomers may be yet another way in which proteins can be made thermophilic.     

The structure of E.coli soluble inorganic pyrophosphatase at 2.7 A resolution

Due to retyping the authors' names when transferring correctionsat the first proof stage, a typographical error was introduced.The correct spelling of the authors' names appears above.     

Crystallization and atomic resolution X-ray diffraction analysis of antichymotrypsin variants

Crystals of two recombinant antichymotrypsin (rACT) variants have been prepared: variant rACT-T345R crystallizes in space group P2(1) (a = 109.2 A, b = 79.4 A, c = 111.9 A, beta = 116.3 degrees, with 2 molecules in the asymmetric unit), and variant ACT' crystallizes in space group P2(1)22(1) (a = 69.7 A, b = 77.2 A, c = 83.8 A, with one molecule in the asymmetric unit). The latter variant is an engineered dimer having the P3-P3' hexapeptide sequence of the related serpin, alpha 1-proteinase inhibitor, substituted for the corresponding wild-type sequence. Crystals of each variant diffract to a limiting resolution of 2.5 A, which represents the best diffraction yet achieved for a crystalline, inhibitory serpin. The exceptional quality of ACT' crystals probably arises from favorable protein-protein interactions as well as a stabilizing disulfide crosslink engineered between the monomers.     

The structure of E.coli soluble inorganic pyrophosphatase at 2.7 A resolution

Hie structure of E.coli soluble inorganic pyrophosphatase hasbeen refined at 2.7 resolution to an R-factor of 20.9. Theoverall fold of the molecule is essentially the same as yeastpyrophosphatase, except that yeast pyrophosphatase is longerat both the N- and C-termini. Escherichia coli pyrophosphataseis a mixed +ß protein with a complicated topology.The active site cavity, which is also very similar to the yeastenzyme, is formed by seven ß-strands and an -helixand has a rather asymmetric distribution of charged residues.Our structure-based alignment extends and improves upon earliersequence alignment studies; it shows that probably no more than14, not 15–17 charged and polar residues are part of theconserved enzyme mechanism of pyrophosphatases. Six of theseconserved residues, at the bottom of the active site cavity,form a tight group centred on Asp70 and probably bind the twoessential Mg⁺ ions. The others, more spreadout and more positivelycharged, presumably bind substrate. Escherichia coli pyrophosphatasehas an extra aspartate residue in the active site cavity, whichmay explain why the two enzymes bind divalent cation differently.Based on the structure, we have identified a sequence motifthat seems to occur only in soluble inorganic pyrophosphatases.     

Evolutionary conservation of enzymatic catalysis: quantitative comparison of the effects of mutation of aligned residues in Saccharomyces cerevisiae and Escherichia coli inorganic pyrophosphatases on enzymatic activity

Soluble inorganic pyrophosphatase (PPase) is one of the better understood phosphoryl-transfer enzymes and is distinctive in having four divalent metal ions at the active site. Here we determine pH profiles for wild-type Saccharomyces cerevisiae PPase (Y-PPase) and for 14 of its active site variants and consider the effects of active site mutation on the pH-independent parameters and acid dissociation constants that characterize these profiles against the framework of the proposed structure of the activated complex. The results obtained (a) support the current mechanistic model in which a hydroxide ion, stabilized by binding to two metal ions at the active site and by an extended system of hydrogen bonds within the active site, is the nucleophile that attacks enzyme-bound inorganic pyrophosphate and (b) provide evidence that the acid group that is necessary for maximal activity is a water molecule coordinated to a third metal ion, as shown by the general rise in the pKa of this group that is a consequence of almost all of the mutations. We further compare the present results to those previously observed for the corresponding mutations in Escherichia coli PPase [E-PPase; Salminen et al. (1995) Biochemistry 34, 782-791]. Such comparison provides a measure of the extent to which different portions of the active site are conserved. We find that some corresponding mutations have different effects on catalytic function, demonstrating that even in the context of very similar active sites, interactions of the mutated site with less well conserved portions of the enzyme, in this case outside the active site, can lead to different outcomes. On the other hand, one region of the active site is highly conserved, suggesting that it may represent a common feature of phosphoryl-transfer enzymes or a vestige of a primitive ur-PPase active site.     

Stereoscopic transparency: a test for binocular vision's disambiguating power

It has been suggested that to resolve ambiguities implicit in binocular perception of complex visual scenes, the brain adopts a continuity constraint assuming that disparities change smoothly with eccentricity. Stereoscopic transparency is characterized by abrupt changes of binocular disparity across retinal locations. The focus of the present study is how the brain uses the continuity constraint in the perception of stereoscopic transparency despite the presence of abrupt disparity changes. Observers viewed random-dot stereograms of overlapping transparent plane and cylindrical surfaces and had to distinguish between two orientations of the cylindrical surface under conditions of strictly controlled depth fixation. Surprisingly, maximal dot density of the transparent plane at which perception is still veridical dramatically decreases as depth separation between the surfaces grows. Persistence of this relationship, when binocular matching processes at each surface are separated to on and off brightness channels, suggests at least two stages in the underlying computation binocular matching and inter-surface interactions. We show that these phenomena cannot be accounted for by either higher severity of matching with high dot densities or the ability of the denser surface to pull vergence to its depth. We also measure contrast sensitivity and near-far symmetry of the underlying mechanism and propose a model of competitive interactions between dissimilar disparities.