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S J Mentzer

Publications and source records attributed to S J Mentzer.

116 records · Page 7Linked to original sources

Tumor sponge implantation: an in vivo method for studying syngeneic, primary antitumor lymphocyte responses.

Sponge matrices surgically implanted in the s.c. space of the back of normal BALB/c mice were injected with a "regressor" dose of Moloney virus-induced BALB/c tumor cells. The kinetics of the generation of cytotoxic cells within the sponge was studied over a 22-day period in a short-term 51Cr release assay. Cytotoxic activity peaked on Day 16 and then declined to negligible levels by Day 22. No cytotoxicity was detectable when nontransformed BALB/c blast cells, Moloney leukemia virus-induced tumor (LSTRA) cells, or unrelated chemically induced tumor (EL4) cells were used as targets. When the cellular composition of implanted tumor sponges was examined on Day 16, it was found to be 30 to 40% myeloperoxidase-positive cells, 15 to 25% surface immunoglobulin-positive cells, and 40 to 50% theta-positive cells. Treatment with anti-Thy 1.2 plus complement eliminated the cytotoxic response on Day 16. The ratio of T-cells to tumor cells within the sponge was determined by immunofluorescence. Kinetic studies showed that the number of theta-positive cells increased well before cytolytic activity was detected, possibly reflecting increasing numbers of amplifier T-cells or cytotoxic cell precursors. A later decline in theta-positive cells correlated directly with decreased cytotoxicity. Furthermore, onset of cytotoxic activity also correlated with a decline in the percentage of Moloney murine sarcoma virus tumor cells within the sponge. Sponge cells isolated on Day 16 (peak cytotoxicity), mixed with lethal dosages of moloney murine sarcoma virus tumor cells, successfully neutralized the lethal challenge demonstrating the in vivo antitumor efficacy of these effector cells. Sponges were also implanted in mice which had been immunized with single injection of Moloney murine sarcoma virus cells. Inoculation of the sponge with tumor cells resulted in a second set response in which cytotoxic cells appeared much earlier than in unsensitized animals. Cells from spleen, lymph node, or peritoneal cavity of normal or presensitized animals with tumor sponge implants were not cytotoxic, suggesting a highly localized response.

Animals↗

Avoidance of the handicapped: an attributional ambiguity analysis.

We demonstrated a general strategy for detecting motives that people wish to conceal. The strategy consists of having people choose between two alternatives, one of which happens to satisfy the motive. By counterbalancing which one does so, it is possible to distill the motive by examining the pattern of choices that people make. The motive used in the demonstration is the desire we believe most people have to avoid the physically handicapped. Because they do not wish to reveal this desire, we predicted that they would be more likely to act on it if they could appear to choose on some other basis. In two studies we found that people avoided the handicapped more often if the decision to do so was also a decision between two movies and avoidance of the handicapped could masquerade as a movie preference.

Anxiety↗

Semi-dry PhastTransfer detection of biotinylated cell surface molecules.

The PhastTransfer system is a semi-dry electrophoretic unit designed to optimize the transfer of small amounts of protein. Because of its efficiency, we adapted the PhastTransfer system for the detection of labeled membrane molecules. Biotin was used as the membrane molecule label because it permitted the long-term storage of labeled lysates as well as the flexibility of derivatizing several different functional groups. After immunoaffinity separation using magnetic microspheres, the protein was electrophoretically separated with the PhastSystem and transferred with the PhastTransfer unit. Using an avidin-linked enzyme amplification system, less than 10 ng of loaded protein could be detected on the transfer membrane. Based on these findings, the PhastTransfer system is a fast, reproducible, and convenient method for the transfer of small quantities of labeled cell surface protein.

Animals↗

Cell adhesion molecule expression in the sheep thymus.

Cell adhesion molecules are potential regulating factors in both prethymic and intrathymic T cell development. An experimental challenge has been the development of a large animal model that facilitates in vivo studies of both intrathymic development and lymphocyte migration. To extend earlier studies of thymic development, we have developed a panel of monoclonal antibodies (mAb) to a variety of sheep cell adhesion molecules. Immunohistochemistry was used to define mAb reactivity and flow cytometry was used to quantify expression of cell adhesion molecules within the thymus. To facilitate flow cytometry definition of cortical thymocytes, mAbs were developed to the sheep CD1 antigen. Dual parameter flow cytometry provided a phenotypic characterization of cell adhesion molecule expression on both CD1(+) and CD1(-) sheep thymocyte populations. These studies demonstrated significantly enhanced cortical thymocyte expression of three cell adhesion molecules: beta1 integrin (CD29), ICAM-2 and LFA-3. The beta1 integrin cell adhesion molecule was also expressed at higher levels on CD1(+) thymocytes in post-natal lambs as compared to adult sheep. These studies of thymocyte membrane molecule expression should facilitate future investigations of sheep intrathymic development and T lymphocyte immigration.

Animals↗

Dendritic cells in the pathophysiology of sarcoidal reactions.

Dendritic cells play an important role in regulating both normal and pathophysiologic immune responses. Complicating the interpretation of dendritic cell function has been the observation that dendritic cells are not only rare, but can demonstrate multiple maturation/differentiation states. Despite these experimental limitations, the accumulating evidence suggests that dendritic cell are a dynamic migratory population that can be recruited into areas of peripheral inflammation. In the peripheral site of inflammation, dendritic cell function appears to involve the processing of antigen and its subsequent presentation to T lymphocytes. Dendritic cells also appear to be capable of transporting antigen to the regional lymph node through the afferent lymphatics. Dendritic cells can be found in the paracortex where they appear to be interacting with T lymphocytes to provide both membrane-bound and soluble activation signals. The central regulatory role of the dendritic cell in immune responses suggests that sarcoidal reactions, and other mononuclear inflammatory processes, are likely to be clinical entities that reflect perturbed dendritic cell function.

Dendritic Cells↗

Potential mechanism of vasomotor dysregulation after lung transplantation for primary pulmonary hypertension.

BACKGROUND: Vasomotor regulation in the lung is controlled by a dynamic balance between humoral factors and autonomic innervation. Lung transplantation is a unique clinical situation in which vasoregulation is dependent on humoral factors alone. METHODS: We illustrate the problem of vasomotor dysregulation with a lung transplant recipient in whom life-threatening hypoxemia was dramatically reversed with the administration of organic nitrates. The potential mechanism for this dysregulation was explored by exposing human endothelial cells to hypoxic conditions in vitro and analyzing the cells for the expression of pulmonary vasoconstrictor gene transcripts. RESULTS: The hypoxic microenvironment induced a tenfold increase in the transcription of the pulmonary vasoconstrictor genes endothelin-1 and platelet-derived growth factor within 24 hours. The addition of organic nitrates had a dramatic effect on decreasing the levels of vasoconstrictor transcripts within 30 minutes of exposure. CONCLUSION: These findings suggest that a potential mechanism for the clinical effect of organic nitrates is the inhibition of vasoconstrictor synthesis by hypoxic endothelium.

Adult↗

Ethical considerations in lung retransplantation.

The decreased survival of patients undergoing lung retransplantation has raised ethical concerns regarding the "fairness" of using organs for retransplantation. This emphasis on organ utility could have important consequences for the doctor-patient relationship and the practice of retransplantation. In an attempt to balance the responsibilities of individual physicians toward their patients and the responsibilities of transplantation programs toward the public resource of donated organs, we propose a limit on the percentage of organs used for experimental or innovative procedures such as retransplantation. This limit would allow the physician to function as the patient advocate, ensure that organs are realistically allocated to patients most likely to benefit from transplantation, and permit an evolving definition of the medical efficacy of retransplantation.

Ethics, Medical↗