REGULATION OF THE IMMUNE SYSTEM BY SYNTHETIC POLYNUCLEOTIDES : III. ACTION ON ANTIGEN-REACTIVE CELLS OF THYMIC ORIGIN

Polyadenylic-polyuridylic acid complexes, a potent adjuvant to the immune response, were tested for action on thymic-influenced and bone marrow-derived lymphocytes in model systems deficient in one or the other of these cells. Adult mice, thymectomized at birth or mice treated with heterologous antithymocyte serum produced 90–95% fewer splenic rosette-forming cells than normal mice in response to an injection of sheep erythrocytes. Intravenous injection of complexes of homoribopolynucleotides, polyadenylic and polyuridylic acids, poly A:U with SRBC restored immunologic competence to NTx- or ATS-treated mice such that they produced normal or near normal levels of splenic RFC. In addition, injection of poly A:U enabled NTx mice to reject allogeneic skin grafts at the same rate as control mice with an intact thymus. Further reduction in residual thymocytes by combining neonatal thymectomy with ATS treatment reduced the number of anti-SRBC RFC induced by poly A:U. Lethally irradiated mice which received SRBC, excess bone marrow cells, and as few as 40,000 thymic lymphocytes were stimulated by poly A:U to produce RFC. No adjuvant effect was observed when irradiated mice received excess thymic lymphocytes and low doses of bone marrow cells with poly A:U. The results suggested that the adjuvant action of poly A:U was exerted on the thymic-influenced, antigen-reactive cell and that restoration of immunocompetence to NTx- or ATS-treated mice was caused by amplification of a small number of residual antigen-reactive cells which were influenced by the thymus in utero before thymectomy, or which survived treatment with ATS

LYMPHOCYTE MEMBRANE DYNAMICS : METABOLIC RELEASE OF CELL SURFACE PROTEINS

Cell surface proteins of normal and neoplastic lymphocytes were labeled with iodide-125I by lactoperoxidase-catalyzed iodination. Incubation of 125I-labeled iodide cells in vitro resulted in the release of iodinated surface proteins at a rapid rate which was dependent on cellular respiration and protein synthesis. Comparisons by disc electrophoresis showed a marked similarity between urea-soluble surface proteins extracted from iodinated cells and iodinated material released by the cells during in vitro incubation. The rate of release of cell surface proteins from thymus cells was three times faster than that of spleen cells or bone marrow-derived thoracic duct lymphocytes. In addition, different proteins were released at different rates as evidenced by the rate of release of 125I of rabbit anti-mouse immunoglobulin specifically bound to mouse spleen cells and comparisons by disc electrophoresis of urea-soluble iodinated surface proteins extracted from cells before and after incubation. The results suggest that a dynamic state exists at the cell surface. The possible role of the release of cell surface proteins in cell regulation and communication is discussed

Regulation of the immune system by synthetic polynucleotides : IV. Amplification of proliferation of thymus-influenced lymphocytes

The role of thymus-influenced antigen reactive cells (ARC) in the immune response was studied with the aid of a potent adjuvant to both antibody formation and cell-mediated immunity, polyadenylic-polyuridylic acid complexes (poly A:U). The polynucleotide complex increased the anti-sheep erythrocyte rosette forming cell response of irradiated mice after thymus cells were exposed to poly A:U in vivo or in vitro prior to injection of bone marrow cells. This direct stimulatory action resulted in an enhancement of the rate of proliferation of ARC in response to antigen and a shortening of the interval between antigenic challenge and the initiation of division in immunocompetent cells. No stimulatory effect of poly A:U on bone marrow derived antibody forming precursor cells was observed.It is suggested that ARC play an important role in the regulation of the length of the induction period, as well as the rate of increase of antibody forming cells in response to some antigenic stimuli.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34171/1/0000459.pd

Chronic Physical Health Consequences of Being Injured During the Terrorist Attacks on World Trade Center on September 11, 2001

Few studies have focused on injuries from the World Trade Center disaster on September 11, 2001. Severe injury has health consequences, including an increased mortality risk 10 years after injury and the risk of mental health problems, such as posttraumatic stress disorder (PTSD). The World Trade Center Health Registry identified 14,087 persons with none of a selected group of preexisting chronic conditions before 2002 who were present during and soon after the World Trade Center attacks, 1,980 of whom reported sustaining 1 or more types of injury (e.g., a broken bone or burn). Survey data obtained during 2003−2004 and 2006−2007 were used to assess the odds of reporting a diagnosis of chronic conditions (heart disease, respiratory disease, diabetes, cancer) up to 5–6 years after the attacks. Number of injury types and probable PTSD were significantly associated with having any chronic conditions diagnosed in 2002–2007. Persons with multiple injuries and PTSD had a 3-fold higher risk of heart disease than did those with no injury and no PTSD, and persons with multiple injuries and with no PTSD had a 2-fold higher risk of respiratory diseases. The present study shows that injured persons with or without comorbid PTSD have a higher risk of developing chronic diseases. Clinicians should be aware of the heightened risk of chronic heart and respiratory conditions among injured persons

Psychological Distress in Parents and School-Functioning of Adolescents: Results from the World Trade Center Registry

Poor school-functioning can be indicative of parent and adolescent mental health and adolescent behavior problems. This study examined 472 adolescents enrolled in the World Trade Center (WTC) Health Registry, with a two-step path analysis, using regression-based models, to unravel the relationships between parent and adolescent mental health, adolescent behavior problems, and adolescent unmet healthcare need (UHCN) on the outcome school-functioning. WTC exposure was associated with UHCN and parental mental health was a significant mediator. There was no evidence that family WTC exposure was associated with UHCN independent of its effect on parental mental health. For the second path, after accounting for the effects of adolescent mental health, behavioral problems, and UHCN, there remained a significant association between parental mental health and school-functioning. Interventions for poor school functioning should have multiple components which address UHCN, mental health, and behavioral problems, as efforts to address any of these alone may not be sufficien

Effect of asthma and PTSD on persistence and onset of gastroesophageal reflux symptoms among adults exposed to the September 11, 2001, terrorist attacks

Background: Little is known about the direction of causality among asthma, posttraumatic stress disorder (PTSD), and onset of gastroesophageal reflux symptoms (GERS) after exposure to the 9/11/2001 World Trade Center (WTC) disaster. Methods: Using data from the WTC Health Registry, we investigated the effects of early diagnosed post-9/11 asthma and PTSD on the late onset and persistence of GERS using log-binomial regression, and examined whether PTSD mediated the asthma-GERS association using structural equation modeling. Results: Of 29,406 enrollees, 23% reported GERS at follow-up in 2011–2012. Early post-9/11 asthma and PTSD were each independently associated with both the persistence of GERS that was present at baseline and the development of GERS in persons without a prior history. PTSD mediated the association between early post-9/11 asthma and late-onset GERS. Conclusions: Clinicians should assess patients with post-9/11 GERS for comorbid asthma and PTSD, and plan medical care for these conditions in an integrated fashion