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Biomedical subjects

J L Murray

Publications and source records attributed to J L Murray.

153 records · Page 9Linked to original sources
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Preschool health education program (PHEP): analysis of educational and behavioral outcome.

A health education curriculum structured around age-appropriate types of behavior that enable children to assume more responsibility for their own health was developed, taught, and evaluated in an early childhood learning center. The curriculum was then field-tested and evaluated in several additional preschools utilizing a design which included comparable nonintervention preschools. The findings indicate that the curriculum contributed to learning and suggest that it has some potential in influencing health related behavior. It is not possible to determine from the findings the precise contribution of the curriculum to the observed changes in children's learning outcomes and health behavior. It is likely that the curriculum and the children's general maturation and development all contributed to the changes observed. The studies demonstrated that the curriculum was effectively structured to be appropriate for the targeted age group, acceptable for use by preschool staff and easily implemented into a variety of preschool settings.

Age Factors↗
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Identification of activated tumor antigen-reactive CD8+ cells in healthy individuals.

We investigated the ability of HER-2 peptide E75, which maps an immunodominant CTL epitope for ovarian and breast tumor-associated lymphocytes (TAL), to activate effector functions in freshly isolated CD8+ cells from healthy individuals. IFN-gamma was rapidly induced by E75 within 20-24 h, in five of six healthy donors, in the presence of IL-12 and was detectable as early as 6 h. The IFN-gamma levels were Ag-concentration dependent. Similar results were obtained with peptides mapping CTL epitopes from two other tumor Ag: folate binding protein (FBP) and amino-enhancer of split of Notch (AES). IFN-gamma was also detected, from freshly isolated, unstimulated PBMC in response to HLA-A2 matched tumors + IL-12 but not of IL-12 alone. The major source of IFN-gamma were CD45RO+ CD8+ cells. Induction of IFN-gamma and IL-2 from CD8+ cells and of IL-12 from dendritic cells (DC) by CD8+ cells reactive with E75 mirrored their induction by the influenza matrix peptide (M1: 58-66) in the same individual. Responses to M1 are used to define the presence of activated memory cells in healthy individuals. Compared to M1 responses E75 recognition induced 2-4-fold lower levels of IL-12 from the same APC and IFN-gamma and IL-2 from the same CD8+ cells. At lower Ag concentrations the endogenous IL-12 induced by E75-reactive CD8+ cells did not reach the threshold required to co-stimulate for IFN-gamma. alphaB7.1 synergized with E75 in increasing the overall levels of IL-2 induced within 24 h. The presence of tumor Ag-reactive activated CD8+ cells in healthy individuals may improve our understanding of the mechanisms of immunosurveillance and regulation of immune responses by tumors.

Breast Neoplasms↗
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Folate binding protein peptide 191-199 presented on dendritic cells can stimulate CTL from ovarian and breast cancer patients.

Tumor associated lymphocytes (TAL) isolated from malignant ascites cultured in media containing interleukin-2 show antitumor responses. These antitumor responses are mediated by cytotoxic T lymphocytes (CTL) which recognize antigen in the context of MHC molecules using T cell receptors. CD8+ CTL recognize peptide epitopes processed from cellular proteins in the context of MHC class I molecules. These peptides have a restricted length of 8-11 amino acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian and 20-50% of breast cancers. We recently found that FBP is the source of antigenic peptides recognized by a number of these CTL-TAL. This indicated that FBP peptides are antigenic in vivo for ovarian and breast CTL-TAL. To define FBP immunogenicity, a peptide defining the epitope E39 (FBP, 191-199) was presented by PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulation of ovarian and breast CTL-TAL by E39 pulsed DC (DC-E39), in the presence of IL-2, rapidly enhanced or induced E39 specific CTL activity. This E39-responder population consisted of cells expressing TCR V beta 9, V beta 13, and V beta 17 families, based on the increase in the percentages of these families in DC-E39 versus DC-NP stimulated TAL. Characterization of immunogenic tumor antigens and of cytokine requirements for induction of functional antitumor effectors may be important for future cancer vaccine developments.

Breast Neoplasms↗
PubMedDate not supplied

Immunological properties of melanoma tumor-infiltrating lymphocytes before and after IL-2-based biotherapies.

Immunological properties of melanoma TILs before and/or after IL-2-based biotherapies were investigated. TILs harvested before therapies, including those for adoptive transfer, proliferated well in culture with IL-2 and displayed cytotoxicity relatively restricted to autologous tumor cells. In contrast, TILs during or at the end of IL-2 based therapies did not proliferate in culture with IL-2. TILs from tumors even harvested 45 days after the end of IL-2 therapy modestly proliferated in culture with IL-2 and showed MHC-nonrestricted cytotoxicity. The number of live tumor cells that were yielded from melanomas during or at the end of IL-2-based therapies significantly decreased in all nine patients with metastatic melanomas, regardless of their clinical responses (2 PR, 2 MR, 2 SD, and 3 PD). Collectively, these results suggest that current IL-2-based therapies resulted in both transient nonresponsiveness of TILs to IL-2 and transient decrease in the number of live tumour cells in most melanoma patients.

Cell Count↗
PubMedDate not supplied

Smoking and causes of death among U.S. veterans: 16 years of observation.

In a 16-year mortality followup of some 293,000 insured U.S. veterans, specific causes of death were studied in relation to smoking status. The main results confirmed earlier findings.Mortality ratios for cigarette smokers as compared with nonsmokers were 1.73 for all causes of death, 1.58 for all cardiovascular diseases, 2.12 for all cancers, and 4.31 for all respiratory diseases. The highest ratios (those greater than 5.0) were observed for cor pulmonale, aortic aneurysm, emphysema and bronchitis, cancer of the pharynx, cancer of the esophagus, cancer of the larynx, and cancer of the lung and bronchus. The greatest excess in deaths in terms of observed numbers minus expected was found for the cardiovascular diseases, in particular for coronary heart disease.Mortality ratios for ex-cigarette smokers who had stopped smoking for reasons other than physicians' orders were much lower compared with nonsmokers than the mortality ratios for current cigarette smokers: 1.21 for all causes, 1.15 for all cardiovascular diseases, 1.39 for all cancers, and 2.08 for all respiratory diseases. For most causes of death, the mortality ratios for ex-cigarette smokers who had stopped smoking for reasons other than physicians' orders varied inversely with the number of years of cessation. For some diseases, the mortality risk for the ex-cigarette smoker returned to normal almost immediately after the cessation of smoking, whereas for others, the return to normal was more gradual. The first group included stroke and the combined category of influenza and pneumonia; the second group included cardiovascular diseases as a whole and coronary heart disease. For still other diseases, although the mortality ratio declined with the length of time smoking was discontinued, substantial excess risks remained even after 20 years of cessation. In this third group were aortic aneurysm, bronchitis and emphysema, and lung cancer-diseases with very high mortality ratios for current cigarette smokers. Parkinson's disease remained the one disease that clearly exhibited a negative association with cigarette smoking.

Adult↗
PubMedDate not supplied

Existent proliferative responses of peripheral blood mononuclear cells from healthy donors and ovarian cancer patients to HER-2 peptides.

Identifying target antigens for tumor-reactive T cells is important for understanding the mechanisms of tumor escape and developing novel anticancer therapies. To date, mainly CTL responses from tumor infiltrating associated lymphocytes (TIL/TAL) to peptide antigens have been investigated in ovarian cancer. In the present study, the ability of self-peptides derived from HER-2/neu proto-oncogene product (HER-2) to stimulate proliferation of PBMC from healthy donors and ovarian cancer patients has been assessed. Peptide sequences from HER-2 containing anchors for major human MHC-class II molecules have been identified. These peptides induced proliferative and cytokine responses at higher frequency in healthy donors than ovarian cancer patients. Four HER-2 peptides corresponding to positions: 396-406, 474-487, 777-789, and 884-899 were able to stimulate proliferation of a larger number of healthy donors than three other distinct HER-2 peptides 449-464, 975-987 and 1086-1098. The pattern of responses of twenty five ovarian cancer patients was different from that in healthy donors. T cell lines were developed by stimulation with peptides from PBMC of an ovarian cancer patient who showed a stable response to all four HER-2 peptides for over six months. Each T cell line was different in its ability to secrete IFN-gamma and IL-10. These results demonstrate (a) that self-peptides from HER-2 can stimulate expansion of T cells in both healthy donors and ovarian cancer patients, and (b) the ability of different peptides to stimulate secretion of different cytokines from lymphocytes of ovarian cancer patients. These results may be important for understanding the mechanisms of tolerance and autoimmunity in human cancers.

Amino Acid Sequence↗