Biomedical subjects

R F Wang

Publications and source records attributed to R F Wang.

At least 37 records · Page 2Linked to original sources

PubMed2000

Heading judgments in minimal environments: the value of a heuristic when invariants are rare.

Observers made systematic heading judgments in two experiments simulating their translation through an environment with only two trees. When those trees converged or decelerated apart, observers tended to follow the invariant information and make heading judgments outside the near member of the pair. When those trees accelerated apart, however, observers tended to follow the heuristic information and make judgments outside the far member, although this result was tempered by the angular separation between the trees and their relative acceleration. The simultaneous existence and use of invariants and heuristics are discussed in terms of different metatheoretical approaches to perception.

Environment↗

PubMed2000

Seeking one's heading through eye movements.

A study of eye movements during simulated travel toward a grove of four stationary trees revealed that observers looked most at pairs of trees that converged or decelerated apart. Such pairs specify that one's direction of travel, called heading, is to the outside of the near member of the pair. Observers looked at these trees more than those that accelerated apart; such pairs do not offer trustworthy heading information. Observers also looked at gaps between trees less often when they converged or diverged apart, and heading can never be between such pairs. Heading responses were in accord with eye movements. In general, if observers responded accurately, they had looked at trees that converged or decelerated apart; if they were inaccurate, they had not. Results support the notion that observers seek out their heading through eye movements, saccading to and fixating on the most informative locations in the field of view.

Adult↗

PubMed1999

Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumor antigen.

In an effort to identify tumor-specific antigens recognized by CD4(+) T cells, an approach was developed that allows the screening of an invariant chain-complementary DNA fusion library in a genetically engineered cell line expressing the essential components of the major histocompatibility complex (MHC) class II processing and presentation pathway. This led to the identification of a mutated form of human CDC27, which gave rise to an HLA-DR4-restricted melanoma antigen. A mutated form of triosephosphate isomerase, isolated by a biochemical method, was also identified as an HLA-DR1-restricted antigen. Thus, this approach may be generally applicable to the identification of antigens recognized by CD4(+) T cells, which could aid the development of strategies for the treatment of patients with cancer, autoimmune diseases, or infectious diseases.

Antigen Presentation↗

PubMed1999

Identification of a novel major histocompatibility complex class II-restricted tumor antigen resulting from a chromosomal rearrangement recognized by CD4(+) T cells.

CD4(+) T cells play an important role in antitumor immune responses and autoimmune and infectious diseases. Although many major histocompatibility complex (MHC) class I-restricted tumor antigens have been identified in the last few years, little is known about MHC class II- restricted human tumor antigens recognized by CD4(+) T cells. Here, we describe the identification of a novel melanoma antigen recognized by an human histocompatibility leukocyte antigen (HLA)-DR1-restricted CD4(+) tumor-infiltrating lymphocyte (TIL)1363 using a genetic cloning approach. DNA sequencing analysis indicated that this was a fusion gene generated by a low density lipid receptor (LDLR) gene in the 5' end fused to a GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase (FUT) in an antisense orientation in the 3' end. The fusion gene encoded the first five ligand binding repeats of LDLR in the NH2 terminus followed by a new polypeptide translated in frame with LDLR from the FUT gene in an antisense direction. Southern blot analysis showed that chromosomal DNA rearrangements occurred in the 1363mel cell line. Northern blot analysis detected two fusion RNA transcripts present only in the autologous 1363mel, but not in other cell lines or normal tissues tested. Two minimal peptides were identified from the COOH terminus of the fusion protein. This represents the first demonstration that a fusion protein resulting from a chromosomal rearrangement in tumor cells serves as an immune target recognized by CD4(+) T cells.

Amino Acid Sequence↗

PubMed1999

Active and passive scene recognition across views.

Recent evidence suggests that scene recognition across views is impaired when an array of objects rotates relative to a stationary observer, but not when the observer moves relative to a stationary display [Simons, D.J., Wang, R.F., 1998. Perceiving real-world viewpoint changes. Psychological Science 9, 315-320]. The experiments in this report examine whether the relatively poorer performance by stationary observers across view changes results from a lack of perceptual information for the rotation or from the lack of active control of the perspective change, both of which are present for viewpoint changes. Three experiments compared performance when observers passively experienced the view change and when they actively caused the change. Even with visual information and active control over the display rotation, change detection performance was still worse for orientation changes than for viewpoint changes. These findings suggest that observers can update a viewer-centered representation of a scene when they move to a different viewing position, but such updating does not occur during display rotations even with visual and motor information for the magnitude of the change. This experimental approach, using arrays of real objects rather than computer displays of isolated individual objects, can shed light on mechanisms that allow accurate recognition despite changes in the observer's position and orientation.

Adult↗

PubMed1999

Diagnosis of mouse hepatitis virus contamination in mouse population by using nude mice and RT-PCR.

Mouse hepatitis virus (MHV) infection in laboratory mouse populations is a serious problem, because the MHV infections are known to interfere with research results. Confirmation of indirect serological detection methods by viral isolation is difficult. Reverse transcription plus polymerase chain reaction (RT-PCR) was used to test 94 mouse tissue samples from suspected naturally MHV infected mice. Positive results were only obtained from two colon samples and one mixed sample with colon and liver. The low positive rate is probably due to the virus being rapidly cleared by the MHV antibodies produced in the mouse. However, RT-PCR detection of MHV in nude mice placed in the same cages with other non-nude mice or placed in cages with used dirty bedding, showed a very high positive rate: 10 out of 12 colon samples were positive (83%), and 5 out of 10 faecal samples were positive (50%). A single-tube, single step RT-PCR method and two procedures for isolation of the viral RNA for the RT-PCR assay were also included in this article.

Animals↗

PubMed1999

Human tumor antigens: implications for cancer vaccine development.

The adoptive transfer of tumor-infiltrating lymphocytes along with interleukin 2 into autologous patients resulted in the objective regression of tumor in about 30% of patients with melanoma, indicating that these T cells play a role in tumor rejection. To understand the molecular basis of the T cell-cancer cell interaction we and others started to search for tumor antigens expressed on cancer cells recognized by T cells. This led to the identification of several major histocompatibility complex (MHC) class I restricted tumor antigens. These tumor antigens have been classified into several categories: tissue-specific differentiation antigens, tumor-specific shared antigens, and tumor-specific unique antigens. Because CD4+ T cells play a central role in orchestrating the host immune response against cancer, infectious diseases, and autoimmune diseases, a novel genetic approach has recently been developed to identify these MHC class II restricted tumor antigens. The identification of both MHC class I and II restricted tumor antigens provides new opportunities for the development of therapeutic strategies against cancer. This review summarizes the current status of tumor antigens and their potential applications to cancer treatment.

Amino Acid Sequence↗

PubMed1999

The effect of the use of a counter-torque device on the abutment-implant complex.

STATEMENT OF PROBLEM: Little is known about the condition of the abutment-screw joint before loading, after the development of the preload. PURPOSE: This study examined the tightening force transmitted to the implant with and without the use of a counter-torque device during the tightening of the abutment screw. MATERIALS AND METHODS: Forty Brânemark implants and 10 CeraOne, Estheticone, Procera, and AurAdapt abutments formed the experimental populations. Samples in each group were further divided into 2 groups, 1 group was tightened with a torque controller without the use of a counter-torque device, whereas the other used the counter-torque device. Samples were positioned in a special holder within the grips of a Tohnichi BTG-6 torque gauge for measuring transmitted forces. RESULTS: There were significant differences (P =. 0001) in the tightening forces transmitted to the implant with and without the use of a counter-torque device when tightening the abutment screws. CONCLUSION: An average of 91% of the recommended preload tightening torque was transmitted to the implant-bone interface in the absence of a counter-torque device. In all abutment systems, less than 10% of the recommended preload tightening torque was transmitted to the implant when the counter-torque device was used.

Dental Abutments↗

PubMed1999

Human heading judgments and object-based motion information.

In four experiments, we explored observers' ability to make heading judgments from simulated linear and circular translations through sparse forests and with pursuit fixation on one tree. We assessed observers' performance and information use in both regression and factorial designs. In all experiments we found that observers used three sources of object-based information to make their judgments--the displacement direction of the nearest object seen (a heuristic), inward displacement towards the fovea (an invariant) and outward deceleration (a second invariant). We found no support for the idea that observers use motion information pooled over regions of the visual field.

Computer Graphics↗

PubMed1999

Mechanisms of reorientation and object localization by children: a comparison with rats.

Neurophysiological studies show that the firing of place and head-direction (HD) cells in rats can become anchored to features of the perceptible environment, suggesting that those features partially specify the rat's position and heading. In contrast, behavioral studies suggest that disoriented rats and human children rely exclusively on the shape of their surroundings, ignoring much of the information to which place and HD cells respond. This difference is explored in the current study by investigating young children's ability to locate objects in a square chamber after disorientation. Children 18-24 months old used a distinctive geometric cue but not a distinctively colored wall to locate the object, even after they were familiarized with the colored wall. Results suggest that the spatial representations underlying reorientation and object localization are common to humans and other mammals. Together with the neurophysiological findings, these experiments raise questions for the hypothesis that hippocampal place and HD cells serve as a general orientation device for target localization.

Animals↗

PubMed1999

Cancer therapy using a self-replicating RNA vaccine.

'Naked' nucleic acid vaccines are potentially useful candidates for the treatment of patients with cancer, but their clinical efficacy has yet to be demonstrated. We sought to enhance the immunogenicity of a nucleic acid vaccine by making it 'self-replicating'. We accomplished this by using a gene encoding an RNA replicase polyprotein derived from the Semliki forest virus, in combination with a model antigen. A single intramuscular injection of a self-replicating RNA immunogen elicited antigen-specific antibody and CD8+ T-cell responses at doses as low as 0.1 microg. Pre-immunization with a self-replicating RNA vector protected mice from tumor challenge, and therapeutic immunization prolonged the survival of mice with established tumors. The self-replicating RNA vectors did not mediate the production of substantially more model antigen than a conventional DNA vaccine did in vitro. However, the enhanced efficacy in vivo correlated with a caspase-dependent apoptotic death in transfected cells. This death facilitated the uptake of apoptotic cells by dendritic cells, providing a potential mechanism for enhanced immunogenicity. Naked, non-infectious, self-replicating RNA may be an excellent candidate for the development of new cancer vaccines.

Animals↗

PubMed1999

A radioiodinated 7alpha-O-iodoallyl diprenorphine for mapping opioid receptors.

The aim of the current research has been to validate an original radioiodinated diprenorphine (DPN) derivative suitable for imaging studies of opioid receptors. [(125)I]7alpha-O-iodoallyl diprenorphine (7alpha-O-IA-DPN) was prepared by radioiododestannylation and in vitro and in vivo opioid receptor binding assays were performed with CDF1 mouse brains. In vitro binding studies showed high affinity (K(i)= 0.4 +/- 0.2 nM) for mouse brain membranes. In vivo studies showed 63% specific binding. Ex vivo autoradiography of brain sections confirmed high uptake and retention of [(125)I]7alpha-O-IA-DPN in regions rich in opioid receptors. This new radioiodinated DPN analogue appears to be a potential radioprobe for in vivo visualization of human cerebral opioid receptors with single photon emission computed tomography (SPECT).

Animals↗

PubMed1999

Human tumor antigens for cancer vaccine development.

The adoptive transfer of tumor-infiltrating lymphocytes (TIL) along with interleukin (IL)-2 into autologous patients with cancer resulted in the objective regression of tumor, indicating that T cells play an important role in tumor regression. In the last few years, efforts have been made towards understanding the molecular basis of T-cell-mediated antitumor immunity and elucidating the molecular nature of tumor antigens recognized by T cells. Tumor antigens identified thus far could be classified into several categories: tissue-specific differentiation antigens, tumor-specific shared antigens and tumor-specific unique antigens. CD4+ T cells play a central role in orchestrating the host immune response against cancer, infectious diseases and autoimmune diseases, and we thus have attempted to identify major histocompatibility complex (MHC) class II-restricted tumor antigens as well. The identification of tumor rejection antigens provides new opportunities for the development of therapeutic strategies against cancer. This review will summarize the current status of MHC class I- and class II-restricted human tumor antigens, and their potential application to cancer treatment.

Adoptive Transfer↗

PubMed1999

Evaluation of the implant master cast by means of the Periotest method.

Accurate master casts are essential for the construction of implant-supported prostheses with a precision of fit. The stability of the abutment replicas in the master cast is critical in the accurate reproduction of the patient's oral presentation. The Periotest method is an objective method of quantifying mobility in a tooth and implant. Eighteen gypsum implant master casts containing two brass abutment replicas per cast were evaluated. The abutment replicas were measured three times each for a total of 108 measurements. The mean periotest values and standard deviations were calculated for the master casts and the abutment replicas. The abutment replicas displayed mean periotest values that ranged from +1.3 to -8.0. The study shows that there are significant differences between stable and unstable implant master casts (P = 0.0001, ANOVA-Fisher's protected least significant difference) and abutment replicas (P = 0.0001, Contrast test). The Periotest method will quantify differences in gypsum stone implant master casts as well as the prosthesis supporting brass abutment replicas that are an integral part of the master cast.

Analysis of Variance↗

PubMed1998

Identification and sequencing of a cDNA encoding 6-phosphogluconate dehydrogenase from a fungus, Cunninghamella elegans and expression of the gene in Escherichia coli.

The fungus, Cunninghamella elegans has been widely used in bioremediation and microbial models of mammalian studies in many laboratories. Using the polymerase chain reaction to randomly amplify the insert directly from the single non-blue plaques of a C. elegans cDNA library, then partly sequencing and comparing with GenBank sequences, we have identified a clone which contains C. elegans 6-phosphogluconate dehydrogenase gene. The polymerase chain reaction product was cloned into a plasmid, pGEM-T Easy vector for full insert DNA sequencing. The 6-phosphogluconate dehydrogenase gene (1458 bases) and the deduced protein sequence were determined from the insert DNA sequence. The gene was found by open reading frame analysis and confirmed by the alignment of the deduced protein sequence with other published 6-phosphogluconate dehydrogenase sequences. Several highly conserved regions were found for the 6-phosphogluconate dehydrogenase sequences. The 6-phosphogluconate dehydrogenase gene was subcloned and over-expressed in a plasmid-E. coli system (pQE30). The cell lysate of this clone has a very high 6-phosphogluconate dehydrogenase enzyme activity. Most of the recombinant protein in this system was formed as insoluble inclusion bodies, but soluble in high concentration of urea-buffer. Ni-NTA resin was used to purify the recombinant protein which showed 6-phosphogluconate dehydrogenase enzyme activity. The recombinant protein has a predicted molecular size correlating with that revealed by sodium dodecylsulfate-polyacrylamide gel electrophoresis analysis. The C. elegans 6-phosphogluconate dehydrogenase was in a cluster with yeast' 6-phosphogluconate dehydrogenase in the phylogenetic tree. Bacterial 6-phosphogluconate dehydrogenase and higher organisms' 6-phosphogluconate dehydrogenase were found in different clusters.

Amino Acid Sequence↗

PubMed1998

A breast and melanoma-shared tumor antigen: T cell responses to antigenic peptides translated from different open reading frames.

Infusion of TIL586 along with IL-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. Here, we report that screening a cDNA library from the 586mel cell line using CTL clones derived from TIL586 resulted in the isolation of a gene, CAG-3 (cancer Ag gene 3). Sequence analysis revealed that CAG-3 encodes an open reading frame identical to NY-ESO-1, which was recently reported to be recognized by autologous serum from a patient with esophageal cancer. Thus, NY-ESO-1 appears to be an immune target for both Ab- and T cell-mediated responses. Significantly, NY-ESO-1-specific CTL clones were capable of recognizing two HLA-A31-positive fresh and cultured breast tumors. To our knowledge, this represents the first direct demonstration that tumor-specific CTL clones can recognize both breast and melanoma tumor cells. A 10-mer antigenic peptide ESO10-53 (ASGPGGGAPR) was identified from the normal open reading frame of NY-ESO-1 based on its ability to sensitize HLA-A31-positive target cells for cytokine release and specific lysis. Interestingly, two additional CTL clones that were sensitized with NY-ESO-1 recognized two overlapping antigenic peptides derived from an alternative open reading frame of the same gene. These findings indicate that CTLs simultaneously responded to two different gene products translated from the normal and alternative reading frames of the same gene. Understanding of this mechanism by which the alternative reading frame is translated may have important implications in tumor immunology.

Amino Acid Sequence↗

PubMed1998

Development of a retrovirus-based complementary DNA expression system for the cloning of tumor antigens.

A new retroviral system has been developed for the generation of a cDNA library and the functional cloning of tumor antigens. These retroviral vectors contain a cytomegalovirus promoter in the 5' long terminal repeat, an extended packaging signal for rapid production of high-titer retroviral particles, and many convenient cloning sites for cDNA library construction. The vesicular stomatitis virus G protein has been used to generate pseudotype retroviral particles to enable efficient viral infection. Using this system, viral titers in the range of 10(6) colony-forming units/ml could be generated routinely, and a high transduction efficiency in human primary cells, including fibroblasts, was achieved. In addition, a new procedure has been devised for screening a retrovirus-based cDNA library without a functional selection. The utility of this system was demonstrated by constructing a retrovirus-based cDNA library and re-isolating the NY-ESO-1 tumor antigen from a cDNA library using an antigen-specific CTL. This approach can facilitate the identification of novel tumor antigens recognized by T cells without knowledge of MHC class I restriction elements and is generally applicable for the isolation of any gene as long as a biological assay is available.

3T3 Cells↗

PubMed1998

Recognition of an antigenic peptide derived from tyrosinase-related protein-2 by CTL in the context of HLA-A31 and -A33.

Tumor-infiltrating lymphocytes (TILs) derived from tumor-bearing patients recognize tumor-associated Ags presented by MHC class I molecules. The infusion of TIL586 along with IL-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. Two T cell epitopes derived from tumor Ags, tyrosinase-related protein (TRP)-1 and TRP-2, were shown to be recognized by HLA-A31 restricted TIL586 and its T cell clones. In this study we tested the hypothesis that these two peptides can be recognized by CTL from non-HLA-A31 patients with melanoma. It was found that both peptides were capable of binding to HLA-A3, -A11, -A31, -A33, and -A68 of the HLA-A3 supertype. Importantly, we found that HLA-A33-positive TIL1244 and its T cell clones can recognize TRP197-205 presented by both HLA-A31 and -A33 molecules, suggesting that a single TCR can recognize peptide/A31 and peptide/A33 complexes. However, peptide titration experiments showed that the affinity of TCR receptor to peptide/A33 could be higher than that to the peptide/A31. These studies have important implications for the development of peptide-based cancer vaccines.

Antigens, Neoplasm↗