Citations

This study, through retrospective review, examines the injury rate of selected disable skiing populations in general and as compared to able-bodied skiers in areas where comparison was possible. Data on disabled skiers gathered from instructional programs at multiple sites indicate that the disabled skier had a very low rate of injury occurrence. Where comparison could be make, it was found that there was no significant difference in overall injury rates between able-bodied and physically disabled skiers. Disabled skiers appear to sustain less severe injuries, and they do not show the trend in increasing injury rates that able-bodied skiers in this study show. In addition, the uphill transport of skiers with a disability who use sit- or mono-skis was exam ined in one large program and found to be efficient and exceedingly safe, with no injuries reported. A major limitation of this study is the inconsistency in methods of data collection and reporting. There is a need for further prospective studies in the general able-bodied and disabled skiing populations with direct comparisons of rate, location and severity of injury, type of disability, and experience level of the skier. We hope that this study will stimulate more ski areas to allow disabled skiers on their slopes, even it limited to participation in supervised, instructional programs.

The methods and materials for ACL reconstruction are important issues for the practicing orthopaedic sur geon. In this study a model was developed to study the biological and biomechanical characteristics of a patel lar tendon autograft used for ACL reconstruction. Spe cifically it was hypothesized that since vascularity of these grafts reflects their "healthiness," strength and vascularity should be inversely related in the early pe riod after implantation. Using an over the top technique, a patellar tendon graft was placed in three groups of dogs and studied at 37, 57, and 120 days. Vascularity of the grafts was measured using technetium-tagged red blood cells, and percent water by weight was determined by dessication. Tensile testing to failure was performed using an MTS machine. The grafts became more vascular, more hydrated, less stiff, and less strong (by 4 weeks) than controls. By 16 weeks the vascular response was subsiding but the grafts remained only 40% as strong as controls. Percent water increased significantly over controls for all time periods. Decrease in strength correlated poorly with vascularity but correlated well with increase in percent water. These findings suggest that the change in strength of an intraarticular ACL replacement relates more to a basic rearrangement of its collagen-ground substance relationships, and that vascularity may re flect the inflammatory response bringing about these changes. The model developed in this study serves as a basis for further studies, and the findings reveal important information about the behavior of ACL graft ing materials.

Proteolytic processing of the amyloid precursor protein (APP) by β-secretase, β-site APP cleaving enzyme (BACE1), is the initial step in the production of the amyloid β (Aβ) peptide, which is involved in the pathogenesis of Alzheimer's disease. The normal cellular function of the prion protein (PrP C ), the causative agent of the transmissible spongiform encephalopathies such as Creutzfeldt–Jakob disease in humans, remains enigmatic. Because both APP and PrP C are subject to proteolytic processing by the same zinc metalloproteases, we tested the involvement of PrP C in the proteolytic processing of APP. Cellular overexpression of PrP C inhibited the β-secretase cleavage of APP and reduced Aβ formation. Conversely, depletion of PrP C in mouse N2a cells by siRNA led to an increase in Aβ peptides secreted into the medium. In the brains of PrP knockout mice and in the brains from two strains of scrapie-infected mice, Aβ levels were significantly increased. Two mutants of PrP, PG14 and A116V, that are associated with familial human prion diseases failed to inhibit the β-secretase cleavage of APP. Using constructs of PrP, we show that this regulatory effect of PrP C on the β-secretase cleavage of APP required the localization of PrP C to cholesterol-rich lipid rafts and was mediated by the N-terminal polybasic region of PrP C via interaction with glycosaminoglycans. In conclusion, this is a mechanism by which the cellular production of the neurotoxic Aβ is regulated by PrP C and may have implications for both Alzheimer's and prion diseases.

Abstract Transforming growth factor β (TGF-β) signaling via Smad proteins occurs in various cell types. However, whereas the biological response to TGF-β can be as distinct as growth promoting (i.e., mesenchymal cells) versus growth inhibiting (i.e., epithelial cells), few discernible differences in TGF-β signaling have been reported. In the current study, we examined the role of Ras in the proliferative response to TGF-β and how it might interface with Smad-dependent and Smad-independent TGF-β signaling targets. TGF-β stimulated Ras activity in a subset of mesenchymal, but not epithelial, cultures and was required for extracellular signal-regulated kinase (ERK)–dependent transcriptional responses. Although dominant negative Ras had no effect on TGF-β internalization or Smad-dependent signaling (i.e., phosphorylation, nuclear translocation, or SBE-luciferase activity), it did prevent the hyperphosphorylation of the Smad transcriptional corepressor TG-interacting factor (TGIF). This was not sufficient, however, to overcome the mitogenic response stimulated by TGF-β, which was dependent on signals downstream of p21-activated kinase 2 (PAK2). Moreover, although the initial activation of Ras and PAK2 are distinctly regulated, TGF-β–stimulated PAK2 activity is required for Ras-dependent ERK phosphorylation and Elk-1 transcription. These findings show the requirement for crosstalk between two Smad-independent pathways in regulating TGF-β proliferation and indicate that the mechanism(s) by which TGF-β stimulates growth is not simply the opposite of its growth inhibitory actions. [Cancer Res 2007;67(8):3673–82]

We reviewed the records of pregnant diabetic women attended at Mayo Clinic during the years 1950–79 and matched each nonaborted diabetic pregnancy with two control pregnancies. Abortions occurred in 49 of 277 diabetic pregnancies (17.7%). The relative risk of other adverse outcomes of pregnancy (± 95% confidence interval) in comparison with controls was as follows: perinatal mortality, 7.0 (3.6–13.8); major congenital birth defects, 6.3 (2.8–14.2); and respiratory distress, 9.0 (4.5–17.9). Diabetic ketoacidosis resulted in fetal death in 5 of 18 cases. Patients with mean fasting blood glucose levels of ≤ 140 mg/dl had a perinatal mortality of 81 per 1000 births and an incidence of respiratory distress and congenital birth defects of 18.9% and 9.9%, respectively. Patients with mean blood glucose levels > 140 mg/dl had corresponding rates of 306 per 1000, 20.4%, and 11.2%, respectively. Hydramnios occurred almost exclusively in diabetic women, and its presence was associated with a twofold increase in the frequency of perinatal death. Analysis of diabetic pregnancy outcome by decade showed no appreciable decrease in the occurrence of perinatal mortality, congenital birth defects, or respiratory distress over the 30-yr period.

Abstract In a recent paper Howard (1932) claims to have shown, by three methods, that the "expected" osmotic equilibria exist between the yolk and white of a hen's egg. Johlin (1933) has criticized her technique of cryhydric measurement and re-asserted that the yolk and white of an egg hive different values for depression of freezing point. Although Needham (1931) and Meyerhof (1931) have considered the possibility of the outer layer of yolk having a lower osmotic pressure than the inner, Howard gives no experimental evidence indicating the existence of an osmotic gradient within the yolk. The methods she used being apparently incapable of showing the difference in osmotic pressure between the whole yolk and the whole white of an egg were presumably unable also to detect the osmotic gradient in the yolk. Grollman's (1931) criticisms of the Hill thermo-electric method for the measurement of vapour pressures when employed with viscous solutions were repeated by Howard, with no other evidence than that it gave results which disagreed with her own. In particular, Bateman's low vapour pressure depression found in mixtures of egg yolk and egg white are declared to be incompatible with high vapour pressure depressions for yolk. It is strange that in the differentiation of the properties of egg yolk and white so many authors should have considered the yolk as homogeneous. It is a well-known fact that the formation of an egg yolk occurs by daily deposits in the ovary of the hen. These extend over several days and that the integrity of the daily deposit is maintained more or less for many days is evidenced by observation of the spherical zones in the yolk of a frozen egg that has been sectioned. Also it is easy to withdraw from the centre of the yolk, using a fine pipette, white yolk which is different chemically from the surrounding yellow yolk. Since no membrane is known to separate these two kinds of yolk nor the daily deposit of yolk, the existence of this non-homogeneity within the yolk must be an indication of the slowness of equilibration inside a hen's egg. Hence, when one speaks of the difference in osmotic pressure of average egg white and average egg yolk, no conclusions can be drawn logically regarding the difference in osmotic pressure on opposite sides of the vitelline membrane. As the Hill thermoelectric method of measuring vapour pressure requires but small quantities of solution, it was of interest to use this micro method to study the difference in osmotic pressures of samples of yolk and white obtained on opposite sides of the membrane.

Objective: Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population. Design and setting: In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies). Main outcome measures: Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence. Results: We identified 130 incident cases for an overall rate of 8.6 cases per 100 000 person-years. There was a significant secular trend, with incidence increasing from 1.1 per 100 000 early in the study to 19.6 per 100 000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100 000 for collagenous colitis and 5.5 per 100 000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100 000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis). Conclusions: The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex.