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D H Wagner

Publications and source records attributed to D H Wagner.

7 recordsLinked to original sources
PubMed1996

Rescue of thymocytes from glucocorticoid-induced cell death mediated by CD28/CTLA-4 costimulatory interactions with B7-1/B7-2.

During the differentiation of thymocytes to mature T cells the processes of positive and negative selection result in signals that either protect thymocytes from cell death, or delete, through apoptosis, thymocytes with self-reactive T cell receptors (TCR). Glucocorticoids have been shown to induce thymocyte apoptosis and are produced within the thymic microenvironment. Furthermore, steroid-induced apoptosis of thymocytes has been suggested as a potential mechanism for removal of nonselected thymocytes. In this report, we demonstrate that thymocytes can be rescued from glucocorticoid-induced apoptosis by incubation with cells that express high levels of B7-1 or B7-2. In addition, the ability to be rescued by B7-1 and/or B7-2 can precede expression of the TCR. We demonstrate that CD3(+)-depleted or CD3+/ TCR-beta(+)-doubly depleted thymocytes can be rescued from glucocorticoid-induced apoptosis through the interaction of CD28 or CTLA-4 on thymocytes with cells bearing high levels of B7-1 or B7-2. Furthermore, these transfected cells are major histocompatibility complex (MHC) class II negative and, while they may express MHC class I, there is no preferential rescue of CD8+ thymocytes in the presence of glucocorticoids. Together, these data suggest that the rescue of thymocytes from glucocorticoids can be independent of the TCR. We also demonstrate that, in addition to CD28, CTLA-4 is expressed on thymocytes, suggesting that rescue from glucocorticoid-induced cell death can be mediated by both CD28 and CTLA-4. A CTLA-4Ig fusion protein which binds to both B7-1 and B7-2 was shown to completely block the rescue of thymocytes from glucocorticoid-induced cell death. Therefore, we conclude that interactions between B7-1/B7-2 and CD28/CTLA-4 are sufficient and necessary for rescue of thymocytes from glucocorticoid-induced cell death.

Abatacept↗
PubMed1994

Role of the CD40-CD40 ligand interaction in CD4+ T cell contact-dependent activation of monocyte interleukin-1 synthesis.

Most studies of the induction of cytokine synthesis in monocytes have employed an exogenous triggering agent such as lipopolysaccharide. However, in nonseptic inflammatory responses (e.g. rheumatoid arthritis) monocyte activation occurs as a result of T cell-generated signals. In previous reports, we and others have demonstrated that contact-dependent T cell-generated signals are capable of contributing to macrophage activation. We have shown that plasma membranes from anti-CD3 activated purified peripheral CD4+ T cells (TmA) but not from resting CD4+ cells (TmR) induce monocytes to synthesize interleukin (IL)-1 in the absence of co-stimulatory cytokines. Studies to determine the expression kinetics of the molecule(s) unique to activated CD4+ T cells which interact with monocytes to induce IL-1 revealed that optimal expression occurred at 6 h post activation. This matched the previously reported kinetics of expression of CD40 ligand (CD40L) on activated peripheral T cells, implicating the CD40-CD40L interaction as a candidate for the initiator of the IL-1 signaling event. The ability of TmA to induce IL-1 synthesis in resting monocytes could be markedly reduced by addition of a monoclonal anti-CD40L antibody, 5c8. In addition, a monoclonal anti-CD40 IgM (BL-C4) proved dramatic in its ability to induce resting monocytes to synthesize IL-1. In summary, these results demonstrate that the CD40-CD40L interaction provides a critical component of CD4+ T cell contact-dependent activation of monocyte IL-1 synthesis.

Antigens, CD↗
PubMed1990

Abnormal protein translocation as the elusive cause of cystic fibrosis: an hypothesis.

Despite the recent rapid advances in isolation of the abnormal gene responsible for cystic fibrosis, there remains the need to explain the mechanism by which a single gene mutation causes the widespread clinical effects seen in this disease. Careful review of the otherwise unexplained abnormalities of cystic fibrosis from the perspective of cell biology reveals the following common features: (1) all these abnormalities involve proteins which are either (A) inserted into cell membranes in the RER and arrested after partial translocation or (B) inserted into RER membranes and fully translocated to be compartmentalized away from the cytosol in secretory vacuoles, lysosomes or peroxisomes; (2) all the involved proteins have minor abnormalities in their physicochemical properties or activity functions; (3) none of the involved proteins are missing or totally deficient in function; (4) final compartmentalization of the involved proteins is unaffected. These observations have directed our attention to the process by which most proteins are inserted into and translocated across lipid bilayer membranes, namely the signal peptide mechanism. This mechanism, not previously examined in cystic fibrosis, is reviewed in detail. Of the major proteins controlling signal peptide translocation, deficiencies in the function of signal peptidase activity appear most capable of causing the effects seen in cystic fibrosis.

Animals↗
PubMed1984

Identifying the right nurse manager. An objective selection process.

Over the past 3 years, 15 successful nurse managers have been chosen using an objective selection process developed by the authors. A process to help the nurse executive answer the question, Am I choosing the right person for this job? is described. Through the use of an applicant assessment process, a candidate's leadership ability is revealed, and subjectivity in selection is considerably reduced.

Hospitals↗
PubMed1978

A review of one hundred and fifty thyroidectomies following prior irradiation to the head, neck and upper part of the chest.

The records of 150 patients who had operations on the thyroid following prior irradiation to the head, neck and chest regions were analyzed. The over-all incidence of carcinoma of the thyroid in these patients was 32 per cent; however, 8.6 per cent of these were occult microscopic tumors. The technetium scan was found to be a reliable method of identifying nodules of the thyroid, while physical examination proved to be a less accurate method of nodule detection. The multifocal nature of the disease was confirmed in this series in which a 68 per cent incidence of residual carcinoma was detected in patients in whom reoperation was required.

Adenocarcinoma↗