Promoting women's health: redefining the knowledge base and strategies for change.

Promoting women's health involves undertaking a critical gender-based analysis of women's health status and health needs and the knowledge bases which underlie health promotion action. The authors argue that professional and lay definitions of health problems often differ and that these differences stem from a differential emphasis on existing knowledge bases. Here the authors explore the focus of epidemiological, clinical, and experiential knowledge and suggest ways in which each does or does not address many key health issues which women themselves identify as important. Attention is also directed towards women's own suppressed and devalued knowledge as embodied in traditional folk practices and alternative care forms. Recommendations are made to improve existing knowledge bases by transforming some of the value orientations, priorities, methods and the social organization of research. The authors suggest that positive health promotion strategies must be based on an improved knowledge base and must incorporate three key concepts which women emphasize as central--self determination, women-centred values, and a gender-based political analysis. Strategies and methods to achieve these ends are suggested for health educators and policy-makers who wish to develop more positive approaches to promoting women's health.     

The integration of mental and behavioral health into disaster preparedness, response, and recovery

The close interplay between mental health and physical health makes it critical to integrate mental and behavioral health considerations into all aspects of public health and medical disaster management. Therefore, the National Biodefense Science Board (NBSB) convened the Disaster Mental Health Subcommittee to assess the progress of the US Department of Health and Human Services (HHS) in integrating mental and behavioral health into disaster and emergency preparedness and response activities. One vital opportunity to improve integration is the development of clear and directive national policy to firmly establish the role of mental and behavioral health as part of a unified public health and medical response to disasters. Integration of mental and behavioral health into disaster preparedness, response, and recovery requires it to be incorporated in assessments and services, addressed in education and training, and founded on and advanced through research. Integration must be supported in underlying policies and administration with clear lines of responsibility for formulating and implementing policy and practice.     

Generation of antigen-specific cytotoxic T lymphocytes and regulation of cytokine production takes place in the absence of CD3zeta.

The TCR-associated protein CD3zeta plays a major role in regulating the state of responsiveness to peptide-MHC complexes on the surface of antigen-presenting cells. In this paper the requirement of CD3zeta in the generation of cytotoxic T cells was compared with its requirement in cytokine gene activation in two mutant mice: ZKO mice with a disrupted CD3zeta gene and ZTG mice in which a truncated CD3zeta segment was expressed as a transgene on the ZKO background. Upon infection of ZTG mice with lymphocytic choriomeningitis virus (LCMV), antigen-specific cytotoxic T lymphocyte (CTL) responses were detected, identical to responses in wild-type mice. In addition, antigen-specific CTL responses to allogeneic class I and class II MHC in ZTG animals were indistinguishable from those in wild-type animals. However, CTL responses to the same major antigens were not detectable in ZKO mice. We conclude that the signal transduction pathways leading to CTL development and cytokine production can be triggered through TCR in the absence of functional CD3zeta, provided the remainder of the TCR-CD3 complex is expressed at high levels on the cell surface. Surprisingly, IFN-gamma production in response to LCMV followed the same kinetics in ZKO, ZTG and wild-type mice. However, in vitro studies showed that cytokine production in general was abnormally regulated in T lymphocytes from ZKO mice, in contrast to ZTG T cells. Taken together, these studies support the hypothesis that development of CTL can take place in the absence of functional CD3zeta. However, CTL development requires stronger TCR-initiated signal transduction events than induction of cytokine genes.     

Disaster and terrorism: Cognitive-Behavioral interventions

The mental health effects of disaster and terrorism have moved to the forefront in the recent past following the events of 11 September 2001 in the United States. Although there has been a protracted history by mental health researchers and practitioners to study, understand, prevent, and treat mental health problems arising as a result of disasters and terrorism, there still is much to learn about the effects and treatment of trauma. Continued communication among disaster workers, first-response medical personnel, and mental health professionals is part of this process. This paper outlines current knowledge regarding the psychological effects of trauma and best cognitive-behavioral practices used to treat trauma reactions. More specifically, the information presented is a summary of Cognitive-Behavioral Therapy (CBT) interventions that are relevant for responding to and dealing with the aftermath of disasters.     

Minimal effects on immune parameters following chronic anti-TGF-beta monoclonal antibody administration to normal mice

Mice genetically deficient in TGF-beta1 or TGF-beta signaling capacity in T or B cells demonstrate profound immune dysregulation, as evidenced by increased lymph node size, expression of markers of memory/activation on T cells, inflammation in a variety of tissues and development of autoantibodies. However, this constant and complete lack of TGF-beta1 or TGF-betaR signaling may not reflect effects of TGF-beta neutralization using antibodies in mature animals. Thus, the present studies were designed to determine if administration of an anti-TGF-beta monoclonal antibody (neutralizes TGF-beta1, 2 and 3) to mature, normal mice results in evidence of immune dysregulation or immune-mediated pathology. An initial study examined daily administration of 0.25, 0.75 and 2.5 mg/kg of anti-TGF-beta to mice for three weeks, achieving blood levels of as high as 9 mg/ml. Comprehensive hematological and histopathological evaluation showed no evidence of pathology. A second study was designed to extend the antibody treatment period and further examine the functional status of the immune system. Mice were injected with 1 mg/mouse (approximately 50 mg/kg) of anti-TGF-beta (1D11) three times per week achieving circulating blood levels of 1-2 mg/ml. Many parameters of immune status were assessed, including natural killer (NK) cell activity, lymphocyte proliferative responses, phagocytic activity, phenotypic assessment of leukocyte subsets, and serum measurements of proinflammatory cytokines, autoantibodies and immunoglobulin isotypes. In addition, histopathological assessment of heart, lungs, liver, kidney, salivary glands, skin, spleen and lymph nodes was also performed. Very few of the multiple immune parameters examined showed detectable changes in anti-TGF-beta-treated mice. Changes that were observed were primarily restricted to the spleen and included increased spleen cell recoveries, increased percentages of macrophages, decreased percentages of NK cells, decreased phagocytic activity, decreased proliferative responses to mitogens and slight increases in T and B cells displaying an activated phenotype. Many of these same parameters examined in the lymph nodes were not altered by the anti-TGF-beta treatment. The thymus was decreased in size, but altered only slightly in one population of developing T cells. Most of the changes observed were modest and returned to control levels after discontinuation of treatments. The only serological finding was an increase in IgA levels in anti-TGF-beta-treated mice, but not in any other isotype. Finally, there was no evidence of increased inflammation in any of the peripheral tissues examined in the anti-TGF-beta-treated mice. In conclusion, although there were changes in some of the immunological parameters examined in these studies, they were few and typically reversed following discontinuation of treatment. The modest nature of the changes observed in these studies is particularly evident when compared to published data of those same parameters examined in mice genetically deficient in TGF-beta1 or mice having TGF-beta unresponsive T or B cells. Thus, there does not appear to be any significant immune dysregulation detectable after long-term antibody-mediated neutralization of TGF-beta in normal mice.