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Biomedical subjects

R van Lier

Publications and source records attributed to R van Lier.

12 recordsLinked to original sources
PubMed1999

Investigating global effects in visual occlusion: from a partly occluded square to the back of a tree-trunk.

'Classic' occlusion examples, such as a square partly occluded by a rectangle, have given rise to so-called local and global accounts of amodal completion. Without denying the influence of local configurations, I take the position that, in the long run, any theory of amodal completion should account for global properties. After a brief review of local and global accounts, two extensions of the stimulus domain are proposed to further illustrate the necessity of global accounts. The first is the domain of so-called fuzzy regularities, i.e., regularities which are not based on metrical identities. It is argued and demonstrated that observers are even susceptible to these fuzzy regularities and that they complete partly occluded shapes accordingly. The second extension is towards 3D object completion. Theories of object representation that describe intrinsic regularities of objects appear to be most suitable to predict relative preferences of alternative object completions. Consequently, fuzzy object completions, such as the completion of the back of a tree-trunk, can be explained better by global constraints.

Depth Perception↗
PubMed1998

Effects of physical connectivity on the representational unity of multi-part configurations.

While physical connection strongly supports perceptual integration of visual elements or parts into single objects, concavities along an object's contour strongly induce segmentation of objects into different parts. By means of a matching task, we examine whether the segmentation of connected parts and the grouping of disconnected parts imply differences in representational unity. All match trials consisted of either two identical configurations or two 180 degrees rotated versions of an otherwise identical configuration, whereas mismatch trials had one misoriented part. Results show that the 180 degrees matches with the physically disconnected parts were relatively slower than similar matches with physically connected parts, although the connections could be minimal (deep concavities, corner to edge connection). This suggests that the mental operation required for the 180 degrees match has more difficulty with the disconnected parts, indicating a measurably lower degree of representational unity.

Adult↗
PubMed1997

Perceptual grouping measured by color assimilation: regularity versus proximity.

Two powerful grouping principles in visual perception have been studied rather frequently, namely, regularity and proximity. In many cases, however, the impact of either regularity or proximity was examined. The goal of the present research is to provide and test an experimental paradigm on the basis of which the relative strengths of these grouping factors can be studied. The proposed paradigm is based on early Gestalt observations that colors of local elements within a perceptual whole tend to look more like each other than they actually are. Three experiments were set up to test whether this phenomenon of color assimilation can provide a means to compare perceptual groupings induced by regularity and proximity. In all experiments, the stimuli were linear configurations of colored elements with variable distances between the elements. The task of the participants was to compare the color of a single test element with the colors of two different groups of elements. In Experiment 1, for all colors, the color of the test element was judged to be more similar to the color of the elements with which it can be grouped by means of regularity. In Experiment 2, for specific colors, the color of the test element tended to be more similar to the elements with which it can be grouped by means of proximity. Finally, in Experiment 3, configurations with a greater variety of positions were tested, including those yielding conflicting groupings, that is, on the basis of regularity and proximity different groupings were to be expected. The color judgements for these stimuli clearly reflected the competition between the two factors.

Color Perception↗
PubMed1997

The selective muscarinic agonist xanomeline improves both the cognitive deficits and behavioral symptoms of Alzheimer disease.

The therapeutic effects of selective cholinergic replacement using oral xanomeline, an m1/m4 receptor agonist, were assessed in a multicenter study of 343 patients with Alzheimer disease (AD). Patients were randomized to parallel treatment arms (placebo, 25, 50, and 75 mg t.i.d. xanomeline) and followed through 6 months of double-blind therapy and 1 month of single-blind placebo washout. Completer analysis, using the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), revealed a significant treatment effect (75 mg t.i.d. vs. placebo; p = 0.045). Similar assessment of global status, using the Clinician's Interview-Based Impression of Change, was also significant (75 mg t.i.d. vs. placebo; p = 0.022). Treatment Emergent Signs and Symptoms analysis of the Alzheimer's Disease Symptomatology Scale, revealed highly significant (p < or = 0.002) dose-dependent reductions in vocal outbursts, suspiciousness, delusions, agitation, and hallucinations. On end-point analysis, the Nurses' Observational Scale for Geriatric Patients also showed a significant dose-response relationship (p = 0.018). The improvement in ADAS-Cog provides the first clinical evidence of involvement of the m1 muscarinic receptor in cognition. Furthermore, the favorable effects of xanomeline on disturbing behaviors suggest a novel approach for treatment of the noncognitive symptoms of AD. Although adverse effects (mainly gastrointestinal) associated with the oral formulation appear to limit its use, a large-scale study investigating the safety and efficacy of transdermal xanomeline is under way.

Administration, Oral↗
PubMed1996

Cure of disseminated xenografted human Hodgkin's tumors by bispecific monoclonal antibodies and human T cells: the role of human T-cell subsets in a preclinical model.

Cure of a single established human Hodgkin's tumor growing subcutaneously in severe combined immunodeficient (SCID) mice can be achieved with a complex protocol using two bispecific monoclonal antibodies (Bi-MoAb) directed against the Hodgkin's associated CD30 antigen and the T-cell triggering molecules CD3 and CD28, respectively, together with human T cells prestimulated in vitro with Bi-MoAbs in the presence of CD30+ cells. To adapt this model to the clinical situation, disseminated tumors were established in SCID mice by intravenous injection of 2 x 10(7) cells of the Hodgkin's derived cell line L540CY. Treatment of SCID mice bearing disseminated CD30+ Hodgkin's tumors with the combination of CD3/CD30 and CD28/CD30 Bi-MoAbs and naive (ie, not in vitro prestimulated) human T cells resulted in the cure of all appropriately treated animals. T lymphocytes obtained from patients with advanced stage untreated Hodgkin's disease were as effective as lymphocytes from healthy controls. Treatment was effective even when delayed until 2 weeks after tumor inoculation, and application of Bi-MoAbs into SCID mice with circulating human T cells was as effective as injecting the Bi-MoAbs before the lymphocytes. Treatment results with isolated CD4+ and CD8+ human T cells suggest that both subsets are necessary for the Bi-MoAb mediated cure of xenografted human tumors in vivo. The efficacy and practicability of this preclinical immunotherapy protocol support and form the basis for the clinical evaluation of this approach in patients with Hodgkin's disease resistant to standard therapy.

Animals↗
PubMed1995

The role of lymphocyte subsets and adhesion molecules in T cell-dependent cytotoxicity mediated by CD3 and CD28 bispecific monoclonal antibodies.

The cure of human Hodgkin's tumors heterotransplanted into SCID mice can be achieved by two bispecific monoclonal antibodies (Bi-mAb) directed against the tumor-associated CD30 antigen and CD3 and CD28, respectively, and normal peripheral human blood T cells. We investigated the role of lymphocyte subsets and adhesion molecules in this Bi-mAb-mediated cytolysis. CD4+ lymphocytes were the most rapidly expanding subpopulation, but Bi-mAb-directed cytotoxicity was mediated preferentially by CD8+ lymphocytes and effector cells belonging to the CD45RO+ "memory" pool. Blocking of the LFA-1/ICAM-1 or CD2/LFA-3 adhesion pathways by mAb decreased Bi-mAb-mediated cytotoxicity. This was not due to inhibition of aggregate formation between Bi-mAb-coated T lymphocytes and target cells. Cross-linking of LFA-1 or CD2 molecules on lymphocytes prestimulated with Bi-mAb bound to CD3 and CD28 antigen lead to a more pronounced and prolonged rise in the intracellular concentration of free Ca2+. Additional CD2 cross-linking resulted in the tyrosine phosphorylation of distinct proteins. These findings indicate that adhesion molecules play a critical role and function as co-stimulatory signals rather than as cellular contact mediators in CD3 and CD28 Bi-mAb-stimulated T lymphocytes.

Antibodies, Bispecific↗
PubMed1994

Cure of xenografted human tumors by bispecific monoclonal antibodies and human T cells.

Tumor immunotherapy should increase both the number of T cells that kill the tumor and the likelihood that those cells are activated at the tumor site. Bispecific monoclonal antibodies (Bi-mAbs) were designed that bound to a Hodgkin's tumor-associated antigen (CD30) on the tumor and to either CD3 or CD28 on the T cell. Immunodeficient mice were cured of established human tumors when mice were treated with both the CD3-CD30 and the CD28-CD30 Bi-mAbs and then given human peripheral blood lymphocytes that had been incubated with the CD3-CD30 Bi-mAb and cells that expressed CD30. The enrichment of human T cells within the tumor and the fact that established tumors can be cured may indicate in situ activation of both the T cell receptor and the costimulatory pathway.

Animals↗
PubMed1994

Integrating global and local aspects of visual occlusion.

The phenomenon of visual occlusion has frequently been studied by means of two-dimensional line drawings. These drawings may elicit various interpretations. Sometimes a mosaic of shapes is seen, sometimes a shape that partly occludes another shape. In the latter case, observers often have a clear idea about the form of the partly occluded shape. Local and global pattern aspects both seem to be decisive with respect to the preferred interpretation. An attempt is made to integrate these aspects by applying the global-minimum principle to the perceptual complexity of three distinct components of those pattern interpretations: (i) The internal structure, dealing with each of the shapes separately, (ii) the external structure, dealing with the positional relation between these shapes, and (iii) the virtual structure, dealing with the occluded parts of the shapes. The perceptual complexity of each of these three components can be expressed in terms of structural information. The hypothesis that the perceptually preferred interpretation is the one for which the total information load is minimal is tested on many patterns stemming from different studies on pattern completion.

Form Perception↗
PubMed1993

CD30-antigen-specific targeting and activation of T cells via murine bispecific monoclonal antibodies against CD3 and CD28: potential use for the treatment of Hodgkin's lymphoma.

Cross-linking of specific tumor antigens with the T-cell-associated CD3 and CD28 antigens can increase IL-2 secretion, proliferation and antigen-specific cytotoxicity in resting T cells. This cross-linking can be achieved effectively by bispecific monoclonal antibodies (BiMAb) with specificity for both the tumor antigen and CD3 or CD28 antigen, respectively. To take advantage of the enhanced activation of CD3 pre-activated T cells by additional activation via the CD28 antigen, BiMAb OKT3/HRS-3 with reactivity to both CD3 and the Hodgkin's-lymphoma-associated CD30 antigen and the BiMAb 15E8/HRS-3 with reactivity to both CD28 and CD30 antigen were generated by hybridoma fusion. Resting T cells, represented by Jurkat cells (CD3+/CD28+) were specifically activated to produce IL-2 by co-cultivation with an EBV-transformed B-cell line (LAZ509, CD30+/CD19+) only in the presence of the CD30/CD28 cross-linking BiMAb and an additional cross-linking anti-CD3/CD19 BiMAb (OKT3/6A4). Neither the cross-linking BiMAbs alone nor any combination of the monospecific parental MAbs induced a comparable IL-2 production by Jurkat cells in the presence of LAZ509. In addition, using a combination of these BiMAbs, an antigen-dependent cytotoxicity was induced by targeting APC-depleted peripheral blood lymphocytes to CD30+ L540 cells. T cells, previously specifically activated by CD3/CD30 in the presence of CD30 antigen, were cytotoxic to CD30+ cell lines only after incubation with BiMAb anti-CD28/CD30. Neither of the BiMAbs nor any of the parental antibodies induced a comparable effect. Our results indicate that such BiMAbs may offer a new approach for specific immunotherapy of Hodgkin's lymphoma, which takes advantage of cytokine secretion and cytotoxicity of activated T cells.

Antibodies, Monoclonal↗
PubMed1993

Defect of interleukin-2 production and T cell proliferation in atopic patients: restoring ability of the CD28-mediated activation pathway.

We previously reported that T lymphocytes of atopic patients displayed a defect in CD2- and CD3-mediated pathways of cell activation; that defect relied on impairment of interleukin 2 (IL-2) production (Romano, M. F., Valerio, G., Turco, M. C., Spadaro, G., Venuta, S., and Formisono, S., Cell. Immunol. 139, 91, 1992). We have subsequently analyzed T cell response to anti-CD2, -CD3, or -CD28 monoclonal antibodies (mAb) in 40 atopic individuals, including patients subjected to immunotherapy. In the latter group T cell response to anti-CD2 mAbs was normal, while IL-2 production and proliferative response in T lymphocytes stimulated via CD3 was still impaired. Costimulation with anti-CD28 mAb rescued both IL-2 production and proliferative response in all tested patients. Response to CD28-mediated stimulation was more pronounced in atopic than that in normal individuals. Our results indicated that CD28 had a major role in T cell proliferation of atopic patients and provided a model for analyzing CD3/CD28 interactions in regulation of IL-2 gene expression.

Adult↗
PubMed1989

Studies on the monocyte dependence of T-cell proliferation induced by monoclonal antibodies directed against regions I and II of the CD2 antigen.

We produced three murine monoclonal antibodies (mAb) directed against the human T-cell differentiation antigen CD2 (formerly T11) and analysed their epitope specificity by E-rosette inhibition, cross-blocking and proliferation-induction experiments. When added together, two mAb (both IgG1 kappa) were able to induce proliferation in peripheral blood T cells. This proliferation was found to be strictly dependent on the presence of monocytes. The polymorphism of Fc receptors (FcR) expressed on human monocytes for murine IgG1 antibodies, which is readily demonstrable in anti-CD3-induced T-cell activation, was not found in the anti-CD2-driven system. Moreover, mAb directed against the 40,000 MW FcRII were unable to inhibit proliferation induced by the mitogenic anti-CD2 combination. Still, F(ab')2 fragments of the mitogenic anti-CD2 antibody combination could not initiate T-cell mitogenesis, despite their ability to induce a rise in the free intracellular [Ca2+]. The contributions of monocytes and of antibody Fc moieties to T-cell proliferation, induced by combinations of anti-CD2 mAb, will be discussed.

Antibodies, Monoclonal↗