Multiple Myeloma: Interleukin-15 Antagonizes Bone Morphogenetic Protein-Induced Apoptosis and Growth Inhibition.

Multiple myeloma has two distinct features: Expansion of malignant plasma cells within the bone marrow accompanied by skeletal destruction. Bone morphogenetic proteins (BMPs) have been shown to induce apoptosis and inhibit growth in myeloma cells. BMPs are members of the TGF-β superfamily of proteins capable of inducing bone formation, and regulate proliferation, differentiation and apoptosis. We have investigated myeloma cell apoptosis and proliferation with BMP-4 and −6 in concert with the myeloma cell growth factors interleukin (IL)-2, IL-6, IL-10, IL-15, IL-21, tumor necrosis factor (TNF)-α and insulin-like growth factor (IGF)-1. Eight samples of highly purified myeloma cells from patients and a human myeloma cell line, IH-1 (Brenne AT et al. Blood. 2002 May 15;99(10):3756–62.), were used in this study. Cytokine concentrations used in the referred experiments were for BMP-4 20ng/ml, BMP-6 250ng/ml, IL-15 20ng/ml and IL-6 0,1ng/ml, respectively. Growth inhibition was measured in a proliferation assay by methyl-[3H]-thymidine incorporation and apoptosis by annexin V- FITC-binding/PI-uptake on flow cytometry. IL-15 antagonized growth inhibition (Figure A) and prevented apoptosis induced by BMP-4 (Figure B) and BMP-6 in the myeloma cell line IH-1. IL-15 also antagonized the growth inhibition induced by BMP-4 and/or BMP-6 in three out of eight patient samples. Neither IL-6, nor any of the other investigated cytokines were able to rescue the myeloma cells from growth inhibition and apoptosis induced by BMP-4 and -6. Among the investigated cytokines, we found that IL-15 has a unique capability to antagonize BMP- induced apoptosis and growth inhibition in myeloma cells. We examined cleavage of the proapoptotic protein caspase-3 and found that BMP-4 activated caspase-3 in the IH-1 cell line. This activation of caspase-3 was blocked by IL-15 but not by IL-6. We have demonstrated a possible mechanism for myeloma cells to escape apoptosis and growth-inhibition within the bone marrow. Intramedullar levels of IL-15 and BMPs may play a role in the pathogenesis of multiple myeloma. Figure A. Proliferation in response to BMP-4 stimulus Figure A. Proliferation in response to BMP-4 stimulus Figure B. Apoptosis in response to BMP-4 stimulus Figure B. Apoptosis in response to BMP-4 stimulus

Depth Perception in Simple Line Drawings

Three-dimensional interpretation of simple line drawings, composed of two triangles with a common side, was studied through the quantitative measurement of perceived orientation of the surface indicated by a stimulus figure. In a single triangle, depth perception is ambiguous and is not stable even if perceived. In two triangles with a common side, however, depth is stably perceived. Depth effect, defined as the magnitude of the angle formed by the two perceived surfaces, increased linearly as the magnitude of an angle at a vertex facing the common side became larger. The depth effect did not vary significantly for the change of a triangular form when the magnitude of the angle at the vertex facing the common side was constant. These results suggest that the depth effect changes systematically with variation in the triangle's form

Sex Differences in Attributions of Success and Failure

Sex of the stimulus figure did not affect the attributions for success and failure in mathematics by 126 Australian students.

A Correlational Analysis of Symmetry between the Arrowhead and Featherhead Müller-Lyer Illusions

Correlational methods were used to investigate symmetry of effect for the arrowhead and featherhead versions of the Müller-Lyer figure. Two control figures were compared in the determination of baseline levels for measurement of the illusions: a shaft presented without any inducing context, and a shaft with vertical inducing lines attached. In addition, results based on difference-score measures of the illusions were contrasted with results obtained by partial-correlation techniques. Overall, when one considers the results for either one of the arrowhead or featherhead versions, the evidence favours a common underlying mechanism. However, results across the two versions suggest that the mechanisms for the two versions differ fundamentally. In weighing the different kinds of evidence contributing to this conclusion, methodological issues were raised. By obtaining two judgments for each stimulus figure from a large number of subjects, it was possible to demonstrate not only that conventional difference-score measures of illusions are highly unreliable, but also that they can yield biased results.

Personal Space Methodology: Relation between Felt-Figures and Scores on Comfortable Interpersonal Distance Scale

24 males and 24 females paired a self-figure with 8 stimulus figures using both the Comfortable Interpersonal Distance Scale and the Felt-figure Free-placement Technique. The two measures were strongly related although the magnitude of relationship varied by stimulus figure and sex.

Number of Response Alternatives and Spatial Arrangement on a Visual Discrimination Task

Normal children, 30 each from ages 5 and 7 yr., were administered a visual discrimination test through a programmed learning machine. Visual discrimination was defined as a match-to-sample task in which subjects pointed to the geometric form, number, or printed letter of the alphabet that matched the stimulus form. Procedures were designed to eliminate learning variables. Although both age groups performed well, there was a statistically significant difference in the total performance at the two ages. A 3-way analysis of variance showed age, number of response alternatives, and type of stimulus form were significant variables; all interactions were significant. It appeared that the significant variable for the 5-yr.-olds was the type of geometric configuration, while the variable most important for the 7-yr.-olds was the number of response alternatives. Patterns of errors on the most difficult item showed the 5-yr.-olds made errors involving a reversal or rotation of the stimulus figure, while the 7-yr.-olds made errors involving some detail of the stimulus figure.

The Role of Figure Orientation and Apparent Depth in the Perception of the Horizontal—Vertical Illusion

An experiment was performed which examined the role of figural orientation directly, and the role of an inappropriately invoked size-constancy mechanism indirectly, in the actuation and magnitude of the horizontal—vertical illusion. When the vertical line of the stimulus figure was aligned above the horizontal line, the illusory effect was significant and positive; in contrast, when the vertical line was located below the horizontal line, the illusion was negative. Under the assumption that a vertical line can appear as a foreshortened line in depth, these findings support an explanation based on the operation of a misapplied size-constancy mechanism.

Development of a Group Test for Assessing Perceptual Abilities

A motion picture test of perceptual abilities has been developed for use with elementary school children. The test has two parts. In Part 1 the child must identify a hidden stimulus figure within one of four designs. In Part 2 the child must identify from four alternatives a figure formed by separate lines which have been presented successively. The test is a self-administering 16-mm sound film and requires about 30 min. of total testing time.

Matching Verbal and Concrete Stimulus Attributes

Reaction time for matching a stimulus figure against 2 of its concrete attributes (shape and number) presented separately but simultaneously in 2 other figures was compared with that for matching the figure against the printed names of the attributes. One group of 5 men and 5 women served in the first task condition and another group in the second. The attributes and attribute-names were presented in both syntactical and non-syntactical orders. No significant task or order effects were found, a result contrary to the hypothesis that selective attention to attributes involves their verbal encoding.

Exploration of Limits of Information Processing in Concept Identification as a Function of Sex and Background-Relevant Information

The over-all aim of this experiment was to explore limits of Ss' conceptual ability to solve problems of high complexity when relevant cues were in the background, i.e., not part of the stimulus figure. Results showed Ss made significantly more errors in concept learning when relevant cues were in the background than on the stimulus figure. The majority of Ss reached limits when concept complexity was 8 bits, with 75% failing to reach criterion to solution when background cues were relevant and 17% when relevant cues were part of the geometric figures.