Macrophage formation of angiostatin during inflammation. A byproduct of the activation of plasminogen

Angiostatin is a potent inhibitor of tumor angiogenesis and the growth of metastatic foci. Recent studies have indicated that neoplastic cells can generate angiostatin directly or in cooperation with tumor-associated macrophages. In studies reported here, we determined whether angiostatin is generated in mice under non-neoplastic settings. Utilizing murine RAW264.7 macrophages and thioglycollate-elicited peritoneal macrophages, we demonstrate that angiostatin-like fragments are generated as a byproduct of the proteolytic regulation of membrane-bound plasmin. Plasmin proteolysis and subsequent loss in membrane-bound plasmin activity requires active plasmin but was unaffected by inhibitors of metalloproteinases. Lysine binding fragments of plasmin, isolated from macrophage-conditioned media utilizing affinity chromatography, appeared as a major (48 kDa) and two minor bands (42 and 50 kDa) in SDS-polyacrylamide gel electrophoresis and were immunoreactive with anti-kringle 1-3 IgG. Each peptide begins with Lys77 and contains the entire sequence of angiostatin. The affinity isolated plasmin fragments inhibited bFGF-induced endothelial cell proliferation. Lavage fluid recovered from the peritoneal cavities of mice previously injected with thioglycollate contained angiostatin-like plasmin fragments similar to those generated in vitro. This is the first demonstration that angiostatin-like plasmin fragments are generated in a non-neoplastic inflammatory setting. Thus, in addition to regulating pericellular plasmin activity, proteolysis of plasmin generates inactive kringle-containing fragments expressing angiostatic properties.     

An assessment of US and Canadian smoking reduction objectives for the year 2000

OBJECTIVES: This study assessed whether US and Canadian smoking reduction objectives for the year 2000 are attainable. The United States seeks to cut smoking in its population to 15%; the Canadian goal is 24%. METHODS: Smoking data were obtained for the United States (1974-1994) and Canada (1970-1995) for the overall populations and several age-sex subpopulations. Analyses estimated trends, future prevalences, and the likelihood of goal attainment. Structural time-series models were used because of their ability to fit a variety of trends. RESULTS: The findings indicate that smoking has been declining steadily since the 1970s, by approximately 0.7 percentage points a year, in both countries. Extrapolating these trends to the year 2000, the US prevalence will be 21% and the Canadian prevalence 24%. CONCLUSIONS: If the current trends continue, the Canadian goal seems attainable, but the US goal does not. The US goal is reachable only for 65-to 80-year-olds, who already have low smoking prevalences. It appears that both countries must increase their commitment to population-based tobacco control.     

In vitro system for differentiating pluripotent neural crest cells into smooth muscle cells

The change in vascular smooth muscle cells (SMC) from a differentiated to a dedifferentiated state is the critical phenotypic response that promotes occlusive arteriosclerotic disease. Despite its importance, research into molecular mechanisms regulating smooth muscle differentiation has been hindered by the lack of an in vitro cell differentiation system. We identified culture conditions that promote efficient differentiation of Monc-1 pluripotent neural crest cells into SMC. Exclusive Monc-1 to SMC differentiation was indicated by cellular morphology and time-dependent induction of the SMC markers smooth muscle alpha-actin, smooth muscle myosin heavy chain, calponin, SM22alpha, and APEG-1. The activity of the SM22alpha promoter was low in Monc-1 cells. Differentiation of these cells into SMC caused a 20-30-fold increase in the activity of the wild-type SM22alpha promoter and that of a hybrid promoter containing three copies of the CArG element. By gel mobility shift analysis, we identified new DNA-protein complexes in nuclear extracts prepared from differentiated Monc-1 cells. One of the new complexes contained serum response factor. This Monc-1 to SMC model should facilitate the identification of nodal regulators of smooth muscle development and differentiation.     

Neuromuscular activation patterns during treadmill walking after space flight

Astronauts adopt a variety of neuromuscular control strategies during space flight that are appropriate for locomoting in that unique environment, but are less than optimal upon return to Earth. We report here the first systematic investigation of potential adaptations in neuromuscular activity patterns associated with postflight locomotion. Astronaut-subjects were tasked with walking on a treadmill at 6.4 km/h while fixating a visual target 30 cm away from their eyes after space flights of 8-15 days. Surface electromyography was collected from selected lower limb muscles and normalized with regard to mean amplitude and temporal relation to heel strike. In general, high correlations (more than 0.80) were found between preflight and postflight activation waveforms for each muscle and each subject: however relative activation amplitude around heel strike and toe off was changed as a result of flight. The level of muscle cocontraction and activation variability, and the relationship between the phasic characteristics of the ankle musculature in preparation for toe off also were altered by space flight. Subjects also reported oscillopsia during treadmill walking after flight. These findings indicate that, after space flight, the sensory-motor system can generate neuromuscular-activation strategies that permit treadmill walking, but subtle changes in lower-limb neuromuscular activation are present that may contribute to increased lower limb kinematic variability and oscillopsia also present during postflight walking.     

Trauma/grief-focused group psychotherapy: School-based postwar intervention with traumatized Bosnian adolescents.

Results of a preliminary effectiveness evaluation of a school-based postwar program for war-exposed Bosnian adolescents are described. The evaluation centered on a manualized trauma/grief-focused group psychotherapy protocol for war-traumatized adolescents based on 5 therapeutic foci: traumatic experiences, trauma and loss reminders, postwar adversities, bereavement and the interplay of trauma and grief, and developmental impact. Fifty-five secondary school students (81% girls; age range?=?15–19 years, M?=?16.81) from 10 Bosnian schools participated in the evaluation. Students completed pregroup and postgroup self-report measures of posttraumatic stress, depression, and grief symptoms and postgroup measures of psychosocial adaptation and group satisfaction. The evaluation yielded preliminary but promising results, including reduced psychological distress and positive associations between distress reduction and psychosocial adaptation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Trauma- and grief-focused intervention for adolescents exposed to community violence: Results of a school-based screening and group treatment protocol.

This study assessed the prevalence of trauma exposure among middle school students and evaluated the effectiveness of a school-based, trauma- and grief-focused group psychotherapy protocol in treating a subset of students with severe exposure, posttraumatic stress disorder (PTSD), and functional impairment. Using a stratified screening procedure, 812 students completed a screening survey; 58 students (7.1% of those surveyed) met criteria for group treatment, and 26 students participated in the group. Group participation was associated with improvements in posttraumatic stress and complicated grief symptoms and in academic performance. Results suggest that students who are exposed to severe levels of community violence often may not be identified or treated. The findings also suggest that severe PTSD in adolescence may be associated with impaired school functioning, and that a reduction in PTSD symptoms may be related to academic remediation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Creating trauma-informed systems: Child welfare, education, first responders, health care, juvenile justice.

Children and adolescents who are exposed to traumatic events are helped by numerous child-serving agencies, including health, mental health, education, child welfare, first responder, and criminal justice systems to assist them in their recovery. Service providers need to incorporate a trauma-informed perspective in their practices to enhance the quality of care for these children. This includes making sure that children and adolescents are screened for trauma exposure; that service providers use evidence-informed practices; that resources on trauma are available to providers, survivors, and their families; and that there is a continuity of care across service systems. This article reviews how traumatic stress impacts children and adolescents' daily functioning and how various service systems approach trauma services differently. It also provides recommendations for how to make each of these service systems more trauma informed and an appendix detailing resources in the National Child Traumatic Stress Network that have been produced to meet this objective. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Core Curriculum on Childhood Trauma: A tool for training a trauma-informed workforce.

Recognition of the nationwide high prevalence of psychological trauma in children and adolescents, combined with increasing awareness of the far-reaching adverse consequences of childhood trauma, have led to calls to develop a trauma-informed mental health workforce. We describe the initial pilot test of the Core Concepts portion of the Core Curriculum on Childhood Trauma, as conducted in a large graduate school of social work. The Core Curriculum uses detailed case vignettes of trauma-exposed youth and families, combined with problem-based learning methods, to promote two primary learning aims: (a) to enhance the development of foundational trauma-related conceptual knowledge, and (b) to accelerate the acquisition of trauma-informed clinical reasoning and clinical judgment. Vignettes are presented in segments to simulate gathering, organizing, drawing meaning from, and making decisions based on information in professional practice. After each segment, the facilitator helps learners to summarize relevant facts, develop hunches and hypotheses, identify learning issues, and plan next steps. The Curriculum was very favorably received by students and was associated with marked increases in self-efficacy in applying the Core Concepts to work with trauma-exposed youth and families. We discuss ways in which the Curriculum can be used, especially as a foundation for training in specific evidence-based treatment protocols, to help prepare a national mental health workforce capable of implementing trauma-informed evidence-based practice. (PsycINFO Database Record (c) 2011 APA, all rights reserved)