Ronald H. Stevens

T-Lymphocyte Variant of Hairy-Cell Leukemia

Immunohematologic studies on cells from a patient with the clinicopathologic syndrome of hairy-cell leukemia showed that the neoplastic cells had receptors for sheep erythrocytes and therefore had human T-lymphocyte characteristics. The leukemic cells did not have the membrane receptors or immunoglobulin markers of B lymphocytes or monocytes nor did they synthesize immunoglobulin. A lymphoid cell line established in vitro from the cells had the same T-lymphocyte characteristics. The lymphoid cell line is positive for tartrateresistant acid phosphatase, forms rosettes with untreated sheep erythrocytes, and reacts with an anti-T-lymphocyte antiserum. Thus the syndrome of hairy-cell leukemia may occasionally result from the neoplastic proliferation of T-lymphocytes as well as from the more usual B-lymphocyte form. This situation is analogous to that described previously in chronic lymphocytic leukemia and other lymphoproliferative disorders.

Glucocorticoids Administered In Vivo Inhibit Human Suppressor T Lymphocyte Function and Diminish B Lymphocyte Responsiveness in In Vitro Immunoglobulin Synthesis

The effects of corticosteroid given in vivo on human lymphocyte subpopulation function were investigated using an in vitro system of pokeweek mitogen-stimulated immunoglobulin production. Peripheral blood lymphocytes were obtained from normal volunteers before and 4 h after the intravenous administration of methylprednisolone. Unfractioned peripheral blood lymphocytes showed a consistent decrease (mean congruent with 50%) in immunoglobulin and total protein synthesis after steroid administration. Utilizing separated thymus-derived (T) and bone marrow-derived (B) lymphocyte fractions, the pathophysiology of this alteration in immunoglobulin production was elucidated. B lymphocytes obtained after steroid treatment showed a markedly diminished immunoglobulin response (20% of normal) to normal T lymphocytes and to normal T cells that had been irradiated to remove suppressor T lymphocyte function. All major classes of immunoglobulin (IgG, IgM, and IgA) were affected. T lymphocytes procured after steroid administration were capable of providing normal amounts of T cell help for B cells in immunoglobulin production. However, suppressor T lymphocyte activity, observed with normal T lymphocytes at high T to B cell ratios, was absent from the post-steroid T lymphocytes. This loss of suppressor T lymphocyte function was not due to the presence of excess help as irradiated pre- and poststeroid T cells provided equal amounts of helper activity. On recombining the poststeroid treatment B cells, which are hyporesponsive in immunoglobulin synthesis, with the posttreatment T lymphocytes, which lack suppressor activity, diminished amounts of immunoglobulin were produced which correlate well with the effects observed with unseparated cells. Thus, corticosteroids have differential effects on the lymphocyte populations involved in immunoglobulin biosynthesis. B cell responsiveness is diminished, suppressor T lymphocyte activity is removed, and helper T lymphocyte function is unaffected.

IgG1 is the predominant subclass ofin vivo- andin vitro-produced anti-tetanus toxoid antibodies and also serves as the membrane IgG molecule for delivering inhibitory signals to anti-tetanus toxoid antibody-producing B cells

Peripheral blood leukocytes from individuals immunized with tetanus toxoid can be stimulated by pokeweed mitogen to produce IgG anti-tetanus toxoid antibody (IgG-Tet)in vitro. Previous studies have shown that treatment of these cells with tetanus toxoid or anti-human IgG reagents can inhibit thisin vitro antibody synthesis. We have examined the four IgG subclasses on the surface of B cells for their relative contributions in the anti-IgG antibody-induced inhibition of IgG-Tet production. With all donors, the inclusion of anti-IgG1, but not anti-IgG2,-IgG3, or -IgG4, antiserum resulted in thein vitro inhibition of IgG-Tet synthesis. The magnitude of this inhibition was similar to that induced by treatment of the B cells with tetanus toxoid antigen. When the supernatants from normalin vitro cultures were assayed for IgG-Tet of the various IgG subclasses, it was observed that the IgG-Tet were almost exclusively IgG1. Similar results were obtained when serum IgG-Tet were measured. Thus, IgG1 appears to be the major subclass for (1) thein vivo-produced IgG-Tet, (2) thein vitro-produced IgG-Tet, and (3) the membrane receptor which can selectively convey an inhibitory signal to the IgG-Tet B cell.

Immunoglobulin Synthesis in Hairy Cell Leukaemia

In vitro studies were performed with leukaemic cells from two patients with hairy cell leukaemia in order to define the nature and kinetics of immunoglobulin synthesis by the neoplastic cells. Both patients had clinically and morphologically well‐defined disease and their cells contained abundant tartrate‐resistant acid phosphatase. One patient had associated macroglobulinaemia. The hairy cells had B‐lymphocyte characteristics as determined by fluorescent immunoglobulin staining and surface receptor properties. They synthesized monoclonal IgM and IgG respectively in vitro. The kinetics of immunoglobulin synthesis were different in cells from the two patients as measured by equilibration time, intracellular degradation, and secretion. Permanent cell lines were established with cells from these patients. The lines grow as typical B‐lymphoblastoid cultures and continue to produce tartrate‐resistant acid phosphatase and immunoglobulin. These studies unequivocally demonstrate the B‐lymphocyte nature of the hairy cells in these patients and provide evidence for their clonal origin both in terms of immunoglobulin and enzyme synthesis.

Enhancement of Metacognition Use and Awareness by Means of a Collaborative Intervention

Current views on metacognition consider it a fundamental factor in learning and problem‐solving which in turn has led to interest in creating learning experiences conducive to developing its use. This paper reports on the effectiveness of a collaborative intervention in promoting college general chemistry students’ awareness and use of metacognition. The intervention starts with a cognitive imbalance experience as a trigger for metacognitive reflection, which is then followed by reflective prompting and peer interaction. A quasi‐experimental control and treatment design with 537 and 464 participants, respectively, was implemented. Assessment of metacognition was accomplished by using a multi‐method instrument that consists of a self‐report (Metacognitive Activities Inventory, MCAI) and a concurrent, web‐based tool (Interactive Multimedia Exercises, IMMEX). IMMEX has been shown to allow rapid classification of problem solvers according to their regulatory metacognitive skills. Compared to the control group, the treatment group showed a significant increase in metacognition awareness, as evidenced by the MCAI, increased ability in solving non‐algorithmic chemistry problems of higher difficulty, and with a higher per cent correctness (IMMEX). These findings are consistent with an overall increase in the use of regulatory metacognitive skills by the treatment group. We propose that the meaningful, purposeful social interaction and the reflective prompting instantiated by the intervention act as promoters of metacognition development. It is of particular relevance that these factors are not exclusive to the intervention employed here and can be embedded by practitioners in their instruction.

Cognitive Neurophysiologic Synchronies: What Can They Contribute to the Study of Teamwork?

Objective: Cognitive neurophysiologic synchronies (NS) are low-level data streams derived from electroencephalography (EEG) measurements that can be collected and analyzed in near real time and in realistic settings. The objective of this study was to relate the expression of NS for engagement to the frequency of conversation between team members during Submarine Piloting and Navigation (SPAN) simulations. Background: If the expression of different NS patterns is sensitive to changes in the behavior of teams, they may be a useful tool for studying team cognition. Method: EEG-derived measures of engagement (EEG-E) from SPAN team members were normalized and pattern classified by self-organizing artificial neural networks and hidden Markov models. The temporal expression of these patterns was mapped onto team events and related to the frequency of team members’ speech. Standardized models were created with pooled data from multiple teams to facilitate comparisons across teams and levels of expertise and to provide a framework for rapid monitoring of team performance. Results: The NS expression for engagement shifted across task segments and internal and external task changes. These changes occurred within seconds and were affected more by changes in the task than by the person speaking. Shannon entropy measures of the NS data stream showed decreases associated with periods when the team was stressed and speaker entropy was high. Conclusion: These studies indicate that expression of neurophysiologic indicators measured by EEG may complement rather than duplicate communication metrics as measures of team cognition. Application: Neurophysiologic approaches may facilitate the rapid determination of the cognitive status of a team and support the development of novel adaptive approaches to optimize team function.

Reliable multi method assessment of metacognition use in chemistry problem solving

Metacognition is fundamental in achieving understanding of chemistry and developing of problem solving skills. This paper describes an across-method-and-time instrument designed to assess the use of metacognition in chemistry problem solving. This multi method instrument combines a self report, namely the Metacognitive Activities Inventory (MCA-I), with a concurrent automated online instrument, Interactive MultiMedia Exercises (IMMEX). IMMEX presents participants with ill defined problems and collects students actions as they navigate the problem space. Artificial neural networks and hidden Markov modeling applied to the data collected with IMMEX produce two assessment parameters: the strategy state, which is related to the metacognitive qualities of the solution path employed, and the ability which is a measure of the problem difficulty students can properly handle. The ability values are significantly correlated with the MCA-I scores, and groups of students who performed using more metacognitive state strategies had significantly higher mean MCA-I values than those using fewer metacognitive strategies. This evidence is indicative of convergence between the methods. This instrument can be used diagnostically to guide the implementation of interventions to promote the use of metacognition; it takes little instructional time, is readily available and allows for the assessment of large cohorts.

Artificial neural network-based performance assessments

Abstract We have explored the ability of artificial neural network technologies to generate performance models of complex problem-solving tasks without the detailed a priori knowledge of the nature of the task. To test the generalizibility of this approach we applied this analysis to two diverse content domains—high school genetics and clinical patient management. In both domains, the artificial neural networks, using only the sequence of actions taken while performing the task, generated multiple classification groups defining different levels of competence. The validity of these neural network performance groupings was further established by the good concordance of these classifications with independently derived expert ratings.

Classification of EEG for Affect Recognition: An Adaptive Approach

Research on affective computing is growing rapidly and new applications are being developed more frequently. They use information about the affective/mental states of users to adapt their interfaces or add new functionalities. Face activity, voice, text physiology and other information about the user are used as input to affect recognition modules, which are built as classification algorithms. Brain EEG signals have rarely been used to build such classifiers due to the lack of a clear theoretical framework. We present here an evaluation of three different classification techniques and their adaptive variations of a 10-class emotion recognition experiment. Our results show that affect recognition from EEG signals might be possible and an adaptive algorithm improves the performance of the classification task.

Stimulation and regulation of human IgE production in vitro using peripheral blood lymphocytes

Abstract The ability of human peripheral blood mononuclear cells (PBL) to produce IgE in vitro was examined. The amount of IgE produced was quantitated using a solid-phase double-antibody radioimmunoassay. While cultures of PBL synthesized IgE without pokeweed mitogen (PWM) stimulation (mean 871 pg per culture), the addition of PWM enhanced IgE synthesis in all cultures from 125 to greater than 617% (mean 2502 pg per culture). IgE was first detectable in culture between Days 3 and 4 and steadily increased thereafter up to Day 7. That this was in vitro synthesized IgE and not cytophilic IgE carried over into the cultures was demonstrated by the fact that IgE production was completely inhibited by addition of cycloheximide to the cultures or irradiation of the B cells. This B-lymphocyte IgE production was dependent on the presence of T lymphocytes. However, in contrast to IgG and IgM, high T B -cell ratios in culture only modestly inhibited IgE production. Irradiated T lymphocytes provided helper function without suppression of IgE at high T B -cell ratios. This effect of high numbers of irradiated T lymphocytes on IgE synthesis was distinguishable from their effect on IgG and IgM. There was no correlation between the amount of IgE produced in vitro and the individuals serum IgE level, nor was there a direct relationship between the amounts of IgE, IgG, or IgM produced within the cultures.