Biomedical subjects

J LeFevre

Publications and source records attributed to J LeFevre.

7 recordsLinked to original sources

PubMed1991

Quantification of effector/target conjugation involving natural killer (NK) or lymphokine activated killer (LAK) cells by two-color flow cytometry.

Precise estimates of the frequency of NK- and LAK-target conjugates were obtained by two-color flow cytometry using hydroethidine and calcein as intracellular labels for target cells and effector cells, respectively. These two dyes can easily be used with a standard single-laser flow cytometer with excellent signal separation and dye retention. Hydroethidine labeling did not alter target susceptibility, and calcein labeling did not significantly alter NK function. Excellent agreement was obtained between this flow cytometric method and visual estimation of the frequency of fresh or IL-2-activated human lymphocytes that form conjugates with K-562 target cells. The percentage of cloned NK or LAK cells that form conjugates with K-562 target cells was dependent on the E:T ratio, with extrapolated maximum conjugate frequencies (alpha max) of 40-50%. However, the frequency of lymphocytes forming conjugates with K-562 cells did not closely correlate with the cytolytic activity of a given lymphocyte population. This two color flow cytometric method employing a pair of fluorochromes that do not modify cell membranes or alter cell function in cytotoxicity assays should facilitate further studies of mechanisms involved in the initial stages of target cell recognition by NK and LAK cells.

Cell Survival↗

PubMed1991

Characterization of effector-target conjugates for cloned human natural killer and human lymphokine activated killer cells by flow cytometry.

The present studies demonstrate that the intracellular fluorochromes calcein and hydroethidine can be used for quantification of effector-target conjugates involving cloned human natural killer (NK) or interleukin-2 (IL-2) activated human lymphokine activated killer (LAK) cells by dual color flow cytometry without potential artifacts that might result from extensive modification of effector and/or target cell membranes. Cloned NK cells and LAK cells form conjugates with cultured cell lines regardless of susceptibility to lysis. The strength of the interactions in these conjugates was investigated using a variable speed vortexer. Even relatively gentle vortexing disrupted most conjugates involving fresh human peripheral blood lymphocytes (PBL) but only about one-fourth of conjugates between K-562 cells and human PBL that had been cultured with or without IL-2 by this treatment. The rate of conjugate formation for LAK cells was determined to be about 3 times faster than for cloned NK cells, and both rates are considerably faster than the reported rate of formation of cytotoxic T lymphocyte (CTL) target conjugates. The differences in the rate of conjugate formation are apparently not related to target cell specificity, since LAK cells form conjugates with susceptible and resistant cell lines at comparable rates. When effector-target conjugates are incubated at 37 degrees C in the absence of calcium--thereby precluding lysis--the percentage of conjugated LAK or cloned NK cells decreases logarithmically with time. These results suggest that an initial equilibrium between free and conjugated lymphocytes gradually shifts in favor of unconjugated cells.

Cell Communication↗

PubMed1991

Isolation accelerates reproductive senescence and alters its predictors in female rats.

The process of reproductive senescence in female rats (Rattus norvegicus, Sprague-Dawley strain) was altered by their social environment during adulthood. The incidence of constant estrus (CE), which marks the end of estrous cyclicity, was nearly twice as high in females living in isolation as it was in females living in groups. Isolated females also entered CE at three times the rate of group-housed females. In addition, the characteristics of a rat's estrous cycle when she was young predicted whether or not she would enter CE during reproductive senescence. However, the characteristics of the cycle that predicted if a rat would enter CE were different for isolated females than for females living in groups. In isolated rats, entry into CE was predicted by a pattern of regular cycles followed by irregular cycles, a lordosis reflex of consistently high intensity during irregular cycles, and an absence of spontaneous pseudopregnancies. Furthermore, a long duration of CE was predicted by early cessation of estrous cycles. In rats living in groups, increased estrogenization of the vaginal smears during irregular cycles was the only predictor of entry into CE. In both environments, the onset of an acyclic lordosis reflex predicted the timing of CE. The potential role of ovarian steroids as mediators of these effects is discussed.

Aging↗

PubMed1989

Optimal experience in work and leisure.

Followed 78 adult workers for 1 week with the experience sampling method. (This method randomly samples self-reports throughout the day.) The main question was whether the quality of experience was more influenced by whether a person was at work or at leisure or more influenced by whether a person was in flow (i.e., in a condition of high challenges and skills). Results showed that all the variables measuring the quality of experience, except for relaxation and motivation, are more affected by flow than by whether the respondent is working or in leisure. Moreover, the great majority of flow experiences are reported when working, not when in leisure. Regardless of the quality of experience, however, respondents are more motivated in leisure than in work. But individuals more motivated in flow than in apathy reported more positive experiences in work. Results suggest implications for improving the quality of everyday life.

Adult↗

PubMed1988

Reproductive senescence in female rats: a longitudinal study of individual differences in estrous cycles and behavior.

The longitudinal pattern of reproductive senescence was described in individual female rats from 4 to 18-22 mo of age. There were two subgroups of rats with different patterns of aging. The Constant Estrus (CE) subgroup progressed through regular cycles, irregular cycles, and constant estrus, followed by a return to irregular cycles, and then persistent diestrus. In contrast, the Irregular subgroup skipped constant estrus, maintaining irregular cycles until they entered persistent diestrus. In both subgroups, irregular cycles were a transition between the major reproductive states, although the type of transition was different in each subgroup. In the CE subgroup, the transition was gradual, continuous, and began with the onset of irregular cycles. In contrast, in the Irregular subgroup, the transition did not begin until the end of irregular cycles, suggesting that the process of aging was delayed. Most rats entered constant lordosis, a state characterized by a strong lordosis reflex that could be elicited by manual palpation on each day. The CE subgroup maintained the state once they entered it, whereas the Irregular subgroup intermittently returned to a lordosis reflex intensity characteristic of young rats. In addition, in the CE subgroup, but not the Irregular subgroup, changes in lordosis reflex intensity during aging were coupled to changes in the proportion of estrogenized vaginal smears during the cycle.

Aging↗

PubMed1984

Description of a skills oriented health ethics program.

Continuing change requires that the primary goal of ethics education be the development of competencies to address changing ethical issues. To develop the skill of critical ethical thinking, a two component model was developed. The first component is a two semester hour course in ethical theory. This component is analogous to the theoretical component of a science curriculum and it emphasizes that ethical theory, like scientific theory, is held hypothetically, subject to revision and replacement as it develops in response to "data." The other component, a one semester hour course in health ethics, is designed as the "laboratory" in which theory interacts with ethical problems in health-care situations. Skill development takes place by requiring students to find and defend solutions to ethical dilemmas by applying and refining ethical theory. the ethical issues addressed include but are not limited to current issues in pharmacy. The ongoing evaluation of this model by external evaluators from the funding agency, local consulting faculty, and students has consistently emphasized the value of concrete involvement in cases concomitantly with the exposure to ethical theory.

Competency-Based Education↗

PubMedDate not supplied

Ethics education for clinical pharmacy practice.

A review of the literature on pharmacy ethics found little concern for ethical issues that arise from pharmacist involvement in clinical practice. This lack of recognition and concern for ethical dilemmas that arise from new pharmacist roles has serious implications for clinical practitioners because of their close involvement in patient care and with other professionals. Also, implications for the profession are serious since a lack of internal control invites external control. Pharmacy educators must provide a leadership role in addressing this lack of concern by systematic evaluation and improvement of ethics education. A model of ethics education is presented that is based on a science education model--both a theoretical and a practical component leading to skill development in recognizing and resolving ethical dilemmas. In other words, pharmacy students will be trained to become their own ethics experts through the application of critical ethical thinking.

Education, Pharmacy↗