Culture of murine aortic explants in 3-dimensional extracellular matrix: a novel, miniaturized assay of angiogenesis in vitro

Assays of angiogenesis in vitro are critical to the study of vascular morphogenesis and to the evaluation of therapeutic compounds that promote or inhibit vascular growth. Culture of explanted aortic segments from rats or mice in a 3-dimensional extracellular matrix (ECM) is one of the most effective ways to generate capillary-like endothelial sprouts in vitro. We have modified the classic aortic explant model by placing the aortic segments from mice within small (5.6 mm diameter, 30 microl volume) lenticular hydrogels of type I collagen supported at the edge by nylon mesh rings. This method of culture, referred to as the "miniature ring-supported gel" (MRSG) assay, optimizes handling, cytological staining, and conventional imaging of the specimen and permits use of minimal volumes of reagents in a 96-well tissue culture format. We have used the MRSG assay to quantify the impaired angiogenic response of aged mice relative to young mice and to show that aged mice have significantly decreased sprout formation, but have similar levels of invasion of vascular smooth muscle cells into the supportive ECM. The MRSG assay, which combines low volume, physically robust gels in conjunction with mouse aortic segments, may prove to be a highly useful tool in studies of the process and control of vascular growth.     

Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses

BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. METHODS: We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3. RESULTS: Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. CONCLUSIONS: Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis.     

Compensation in Academic Medicine: Progress Toward Gender Equity

Background Studies have documented substantial salary disparities between women and men in academic medicine. While various strategies have been proposed to increase equity, to our knowledge, no interventions have been evaluated. Objective This paper aims to assess the effect of an identity-conscious intervention on salary equity. Design This study shows comparison of adjusted annual salaries for women and men before and after an intervention. Participants/Setting We studied full time faculty employed in FY00 (n = 393) and FY04 (n = 462) in one College of Medicine. Intervention Compensation data were obtained from personnel databases for women and men, and adjusted for predictors. After verification of data accuracy by departments, comparable individuals within the same department who had different salaries were identified. The Dean discussed apparent disparities with department heads, and salaries were adjusted. Measurements Total adjusted annualized salaries were compared for men and women for the year the project began and the year after the intervention using multivariate models. Female faculty members’ salaries were also considered as a percent of male faculty members’ salaries. Results Twenty-one potential salary disparities were identified. Eight women received equity adjustments to their salaries, with the average increase being $17,323. Adjusted salaries for women as a percent of salary for men increased from 89.4% before the intervention to 93.5% after the intervention. Disparities in compensation were no longer significant in FY2004 in basic science departments, where women were paid 97.6% of what men were paid. Conclusions This study shows that gender disparities in compensation can be reduced through careful documentation, identification of comparable individuals paid different salaries, and commitment from leadership to hold the appropriate person accountable.     

Action during body perception: processing time affects self-other correspondences

The accurate perception of other people and their postures is essential for functioning in a social world. Our own bodies organize information from others to help us respond appropriately by creating self-other mappings between bodies. In this study, we investigated mechanisms involved in the processing of self-other correspondences. Reed and Farah (1995) showed that a multimodal, articulated body representation containing the spatial relations among parts of the human body was accessed by both viewing another's body and moving one's own. Use of one part of the body representation facilitated the perception of homologous areas of other people's bodies, suggesting that inputs from both the self and other activated the shared body representation. Here we investigated whether this self-other correspondence produced rapid facilitation or required additional processing time to resolve competing inputs for a shared body representation. Using a modified Reed and Farah dual-task paradigm, we found that processing time influenced body-position memory: an interaction between body-part moved and body-part attended revealed a relative facilitation effect at the 5 s ISI, but interference at the 2 s ISI. Our results suggest that effective visual-motor integration from the self and other requires time to activate shared portions of the spatial body representation.     

A biomechanical comparison of initial fixation strength of 3 different methods of anterior cruciate ligament soft tissue graft tibial fixation: resistance to monotonic and cyclic loading

BACKGROUND: Tibial fixation of soft tissue grafts continues to be problematic in the early postoperative period after anterior cruciate ligament reconstruction. HYPOTHESIS: No differences exist for resistance to slippage of soft tissue grafts fixed with CentraLoc, Intrafix, or 35-mm bioabsorbable interference screws. STUDY DESIGN: Controlled laboratory study. METHODS: Bovine tibia and hoof extensor tendons were divided into 3 matched groups with 12 tibia and 12 extensor tendons in each group. Within each group, 6 specimens underwent monotonic loading to failure (1 mm/s), and 6 underwent cyclic loading (10,000 cycles, 125-325 N, 1 Hz). RESULTS: No statistically significant differences were noted in mean load to failure or stiffness. The mean load to failure (and stiffness) for the 3 types of fixation were as follows: bioabsorbable interference screw, 631.6 +/- 130.1 N (88.17 +/- 6.79 N/mm); Intrafix, 644.3 +/- 195.2 N (81.65 +/- 16.5 N/mm); and CentraLoc, 791.1 +/- 72.7 N (77.89 +/- 7.07 N/mm). The slippage rates under cyclic loading for the 3 types of fixation were bioabsorbable interference screw, 0.336 +/- 0.074 microm/cycle; Intrafix, 27.2 +/- 31.6 microm/cycle; and CentraLoc, 0.0355 +/- 0.0046 microm/cycle. In this model, CentraLoc proved statistically superior in resistance to cyclic loading compared with the bioabsorbable interference screw (P < .05) and Intrafix (P < .0001). The bioabsorbable interference screw proved statistically superior to Intrafix in resistance to cyclic loading (P < .05). CONCLUSIONS: In this bovine model, CentraLoc and bioabsorbable interference screws provided superior resistance to cyclic loading compared with Intrafix. CLINICAL RELEVANCE: CentraLoc and bioabsorbable interference screws showed superior resistance to cyclic loading, which may indicate an increased resistance to clinical failure.     

Spondyloarthropathy presenting at a young age: case report and review

The diagnosis of juvenile spondyloarthritis (JSA) is rarely entertained in young children who present with back and leg pain. We present a case of a 6-year-old male who presented with a 3-year history of severe back and leg pain and a positive Gower’s sign, and was given a presumed diagnosis of muscular dystrophy. Presenting serologic evaluation included a mildly elevated sedimentation rate and C-reactive protein (CRP). Computed tomography of the pelvis demonstrated large erosions affecting both sacro-iliac joints. Despite the unusually young age of this patient, ankylosing spondylitis seemed the most plausible diagnosis. Following rheumatological evaluation and treatment for JSA, he showed significant clinical improvement. His disease, however, has not entirely remitted with signs of enthesitis at the Achilles tendon and knees. We present this case to illustrate that JSA could account for symptoms at an early age and not considering it could lead to multiple medical visits and diagnoses. To our knowledge, based on a search of the World literature, this would appear to be the youngest case of JSA reported with demonstrable severe sacroiliitis. Presented at the 31st Annual members Meeting of the International Skeletal Society in Malta, September 2004.