Imaging evaluation of chest wall tumors in children.
Explore the source record for details and available documents.
Child↗
Biomedical subjects
M M Davis
Publications and source records attributed to M M Davis.
Testicular serous papillary cystadenomatous tumor of low malignant potential in a child.
Explore the source record for details and available documents.
Child↗
Ligand recognition by alpha beta T cell receptors.
While still incomplete, the first data concerning the biochemistry of T cell receptor-ligand interactions in cell-free systems seem to have considerable predictive value regarding whether a T cell response is strong or weak or suppressive. This data will help considerably in elucidating the mechanisms behind T cell responsiveness. Also of great interest are the first structures of T cell receptor molecules and, particularly, TCR-ligand complexes. These appear to confirm earlier suggestions of a fixed orientation for TCR engagement with peptide/MHC and should form the basis for understanding higher oligomers, evidence for which has also just emerged. We conclude with an analysis of the highly diverse CDR3 loops found in all antigen receptor molecules and suggest that such regions form the core of both TCR and antibody specificity.
Animals↗
Effects of dialogue and therapeutic touch on preoperative and postoperative experiences of breast cancer surgery: an exploratory study.
PURPOSE/OBJECTIVES: To obtain preliminary data and determine the feasibility of a large-scale experimental study to test the efficacy of the Rogerian Science of Unitary Human Beings-based intervention of dialogue and therapeutic touch (TT) on pre- and postoperative anxiety and mood and postoperative pain from breast cancer surgery. DESIGN: Experimental. SETTING: Mid-Atlantic region; ambulatory. SAMPLE: 29 Caucasian and 2 African American English-speaking women with positive breast cancer biopsy (experimental, n = 14; control, n = 17), ranging in age from 31-84 years old (F = 55.6). METHODS: Treatments administered in subjects' homes within seven days prior to surgery and 24 hours after hospital discharge. Experimental treatment consisted of 10 minutes of TT and 20 minutes of dialogue. Control treatment consisted of 10 minutes of quiet time and 20 minutes of dialogue. Data (Spielberger State-Trait Anxiety Inventory. Affects Balance Scale, and Visual Analog Scale-Pain) were collected at the conclusion of each home visit. MAIN RESEARCH VARIABLES: Anxiety, mood, and pain. FINDINGS: The experimental group had lower preoperative state anxiety than the control groups (p = 0.008). No difference was found for preoperative mood. No differences were found for any postoperative measure. CONCLUSIONS: A large-scale study of dialogue and TT would require changes in design and recruitment strategies. IMPLICATIONS FOR NURSING PRACTICE: Nurses may provide more comprehensive care by incorporating dialogue and TT or quiet time into their pre- and postoperative care. Additional research, however, is recommended to determine the differential effects of dialogue, TT, and quiet time on women's experiences with breast cancer prior to incorporating these noninvasive modalities into clinical practice.
Adult↗
Ligand-specific oligomerization of T-cell receptor molecules.
T cells initiate many immune responses through the interaction of their T-cell antigen receptors (TCR) with antigenic peptides bound to major histocompatibility complex (MHC) molecules. This interaction sends a biochemical signal into the T cell by a mechanism that is not clearly understood. We have used quasielastic light scattering (QELS) to show that, in the presence of MHC molecules bound to a full agonist peptide, TCR/peptide-MHC complexes oligomerize in solution to form supramolecular structures at concentrations near the dissociation constant of the binding reaction. The size of the oligomers is concentration dependent and is calculated to contain two to six ternary complexes for the concentrations tested here. This effect is specific as neither molecule forms oligomers by itself, nor were oligomers observed unless the correct peptide was bound to the MHC. These results provide direct evidence for models of T-cell signalling based on the specific assembly of multiple TCR/peptide-MHC complexes in which the degree of assembly determines the extent and qualitative nature of the transduced signal. They may also explain how T cells maintain sensitivity to antigens present in only low abundance on the antigen-presenting cell.
Amino Acid Sequence↗
Kinetics and extent of T cell activation as measured with the calcium signal.
We have characterized the calcium response of a peptide-major histocompatibility complex (MHC)-specific CD4(+) T lymphocyte line at the single cell level using a variety of ligands, alone and in combination. We are able to distinguish four general patterns of intracellular calcium elevation, with only the most robust correlating with T cell proliferation. Whereas all three antagonist peptides tested reduce the calcium response to an agonist ligand, two give very different calcium release patterns and the third gives none at all, arguing that (a) antagonism does not require calcium release and (b) it involves interactions that are more T cell receptor proximal. We have also measured the time between the first T cell-antigen-presenting cell contact and the onset of the calcium signal. The duration of this delay correlates with the strength of the stimulus, with stronger stimuli giving a more rapid response. The dose dependence of this delay suggests that the rate-limiting step in triggering the calcium response is not the clustering of peptide-MHC complexes on the cell surface but more likely involves the accumulation of some intracellular molecule or complex with a half-life of a few minutes.
Amino Acid Sequence↗
Stability of empty and peptide-loaded class II major histocompatibility complex molecules at neutral and endosomal pH: comparison to class I proteins.
The structure and thermal stability of empty and peptide-filled forms of the murine class II major histocompatibility complex (MHC) molecule I-E(k) were studied at neutral and mildly acidic pH. The two forms have distinct circular dichroic spectra, suggesting that a conformational change may accompany peptide binding. Thermal stability profiles indicate that binding of peptide significantly increases the thermal stability of the empty heterodimers at both neutral and mildly acidic pH. Free energies calculated from these data provide a direct measure of this stabilization and show that the empty form of I-E(k) is significantly more stable than that of class I MHC proteins. Furthermore, for the two MHC class II proteins that were analyzed (I-E(k) and I-A(d)), thermal stability was not significantly altered by acidification. In contrast, of four class I MHC molecules studied, three have shown a significant loss in complex stability at low pH. The marked stability exhibited by their empty form, as well as their resistance to low pH, as observed in this study, correlate well with the ability of class II MHC molecules to traverse and bind peptides in acidic endosomal vesicles.
Amino Acid Sequence↗
T cell receptor biochemistry, repertoire selection and general features of TCR and Ig structure.
T cell recognition is a central event in the development of most immune responses, whether appropriate or inappropriate (i.e. autoimmune). We are interested in reducing T cell recognition to its most elemental components and relating this to biological outcome. In a model system involving a cytochrome c-specific I-Ek restricted T cell receptor (TCR) derived from the 2B4 hybridoma, we have studied the interaction of soluble TCR and soluble peptide-MHC complexes using surface plasmon resonance. We find a striking continuum in which biological activity correlates best with the dissociation rate of the TCR from the peptide-MHC complex. In particular, we have found that weak agonists have significantly faster off-rates than strong agonists and that antagonists have even faster off-rates. This suggests that the stability of TCR binding to a given ligand is critically important with respect to whether the T cell is stimulated, inhibited or remains indifferent. It also suggests that the phenomenon of peptide antagonists might be explained purely by kinetic models and that conformation, either inter- or intramolecular, may not be a factor. We have also studied TCR repertoire selection during the establishment of a cytochrome c response, initially using an anti-TCR antibody strategy, but more recently using peptide-MHC tetramers as antigen-specific staining reagents. These tetramers work well with either class I or class II MHC-specific TCRs and have many possible applications. Lastly, we have also tried to correlate the structural and genetic features of TCRs with their function. Recent data on TCR structure as well as previous findings with antibodies suggest that both molecules are highly dependent on CDR3 length and sequence variation to form specific contacts with antigens. This suggests a general "logic' behind TCR and Ig genetics as it relates to structure and function that helps to explain certain anomalous findings and makes a number of clear predictions.
Animals↗
Detection of pulmonary metastases with pathological correlation: effect of breathing on the accuracy of spiral CT.
BACKGROUND: CT of the chest for suspected pulmonary metastases in adults is generally performed using a breath-hold technique. The results may not be applicable to young children in whom breath-holding may be impossible. OBJECTIVE: Determine the effect of breathing on the accuracy of pulmonary metastasis detection by spiral CT (SCT). MATERIALS AND METHODS: Prior to euthanasia four anesthetized dogs with metastatic osteosarcoma underwent SCT with a collimation of 5 mm and a pitch of 2, during both induced breath-hold and normal quiet breathing. Images were reconstructed as contiguous 5-mm slices. Macroscopically evident metastases were noted at postmortem. Hard-copy SCT images were reviewed by ten radiologists, each of whom circled all suspected metastases. SCT images were compared with postmortem results to determine true and false positives. RESULTS: The pathologist identified 132 macroscopically evident pulmonary metastases. For metastasis detection, there was no significant difference between breath-hold SCT and breathing SCT. CONCLUSION: In our animal model, SCT can be performed during normal resting breathing without significant loss of accuracy in the detection of pulmonary metastases.
Animals↗
CD4 augments the response of a T cell to agonist but not to antagonist ligands.
The recognition of peptide variants by the T cell receptor (TCR) has revealed a wide range of possible responses. Here, using a series of CD4+ and CD4- variants of the same T cell hybridoma, we find that while the expression of CD4 converts weak agonists into full agonists, none of the antagonist peptides are efficiently recognized as agonists. Furthermore, in antagonist assays, little difference can be seen in the response of CD4+ and CD4- T cells. Together with previous work showing a marked difference in stability between TCR binding to agonist versus antagonist ligands, these data suggest that CD4 engagement occurs after a TCR-peptide/MHC complex has formed and that it requires a certain minimal half-life of the ternary complex to be fully engaged in signaling.
Amino Acid Sequence↗
A range of CD4 T cell tolerance: partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis.
T cell receptor (TCR) transgenic mice specific for hen egg lysozyme (HEL) were crossed with mice expressing HEL on the thyroid epithelium, on pancreatic islet beta cells, or systemically. Depending on the pattern of HEL expression, deletion of double-positive thymocytes ranged from minimal to complete, and peripheral CD4 cells exhibited graded reduction in TCR expression, in vitro responsiveness, and in vivo helper ability. CD4 cells were least tolerant in TCR/thyroid-HEL and TCR/islet-HEL mice, which developed an extensive lymphocytic thyroiditis or insulitis that nevertheless did not eliminate HEL-expressing endocrine cells. Autoreactive CD4 clones thus escape the thymus under a range of circumstances, retain sufficient function to initiate subclinical autoimmune inflammation when self-antigens are concentrated in the thyroid or pancreas, and may regulate progression of subclinical inflammation to destructive autoimmune disease.
Animals↗
The ontogeny of canine small intestinal submucosa regenerated bladder.
PURPOSE: Small intestinal submucosa has previously been shown to promote regeneration of transitional epithelium, smooth muscle and peripheral nerves in rat and dog bladders. The origin of these regenerated components is presently unknown. This study attempts to define the origin of vascular, smooth muscle and peripheral nerve regeneration. MATERIALS AND METHODS: A total of 22 adult male dogs weighing 25 to 30 kg. underwent partial cystectomy and immediate augmentation with a small intestinal submucosa patch graft. The small intestinal submucosa graft-native bladder interface was marked with permanent marking sutures for future reference. Small intestinal submucosa regenerated bladders were harvested at 2, 3, 4, 6, 8 and 10 weeks after augmentation. The tissue was then studied with routine histology and immunohistochemistry using factor VIII, smooth muscle specific actin (1A4) and neurofilament staining. RESULTS: Results demonstrated that epithelialization of the graft surface was complete by 3 to 4 weeks with normal transitional histology. In the early periods neovascularization was prominent throughout the entire graft, as shown by factor VIII staining. Later more mature vessels were noted. Early in muscle formation sheets of elongated spindle cells extended into the graft from the incised native bladder at both surgical margins and ran parallel to the mucosal surface. At 4 weeks this spindle cell proliferation completely traversed the graft. Trichrome stained sections of the 4-week-old grafts showed no evidence of muscle differentiation and the spindle cells appeared to be fibroblasts. However, these cells stained positive for smooth muscle specific actin (1A4), indicating myogenic potential. Between weeks 4 and 6 the spindle cells became more haphazardly arranged and were separated by loose interstitium. By weeks 8 to 10 there was distinct smooth muscle bundle formation within these areas of proliferating myocytes. Neural regeneration appeared to coincide with smooth muscle development. Early neurofilament positive cells were noted predominantly at the graft-native bladder interface. At 4 weeks neurofilament positive cells were present throughout the graft and by 10 weeks nerve trunks composed of several nerve fibers were identified in association with newly formed smooth muscle bundles. CONCLUSIONS: Small intestinal submucosa serves as a platform for bladder regeneration. Neovascularization smooth muscle and neural regeneration appear to occur through pannus ingrowth from the graft-native bladder interface. Smooth muscle regeneration seems to begin with the maturation of myofibroblasts, which migrate into the graft as early as 2 weeks after augmentation, and it progresses to the formation of distinct smooth muscle bundles by 10 weeks.
Animals↗
Phenotypic analysis of antigen-specific T lymphocytes.
Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.
Amino Acid Sequence↗
Early biochemical signals arise from low affinity TCR-ligand reactions at the cell-cell interface.
The kinetics of acid release by a mixture of T cells and antigen presenting cells were measured with a microphysiometer during a brief exposure to antigenic peptides. We find that some of the early biochemical events that lead to cellular proliferation cause a specific increase in the rate of acid release. The duration of this increase in acid release reflects the life-time of the peptide-MHC complexes. Peptides that form long-lived complexes produce a response that is stable for more than an hour. Serial TCR engagement is suggested by the observation that the amplitude of this stable response can be rapidly shifted up or down with additional agonist peptide or with antibodies that block T cell receptor binding. Cells briefly exposed to a peptide that forms short-lived peptide-MHC complexes produce a response that decays rapidly as peptide is washed away. A quantitative analysis of the kinetics of this decay in acidification demonstrates that intercellular TCR-ligand reactions are rapid, reversible, and of low apparent affinity with < 20% of peptide-MHC ligand bound to a TCR at any one time. These results demonstrate that the fraction of peptide-MHC ligands bound to TCRs at the cell-cell interface is no higher than anticipated from the affinities observed in solution for isolated TCRs and ligands.
Amino Acid Sequence↗
Evolving catalysts in real time.
Explore the source record for details and available documents.
Antibodies, Catalytic↗
Kinetic discrimination in T-cell activation.
We propose a quantitative model for T-cell activation in which the rate of dissociation of ligand from T-cell receptors determines the agonist and antagonist properties of the ligand. The ligands are molecular complexes between antigenic peptides and proteins of the major histocompatibility complex on the surfaces of antigen-presenting cells. Binding of ligand to receptor triggers a series of biochemical reactions in the T cell. If the ligand dissociates after these reactions are complete, the T cell receives a positive activation signal. However, dissociation of ligand after completion of the first reaction but prior to generation of the final products results in partial T-cell activation, which acts to suppress a positive response. Such a negative signal is brought about by T-cell ligands containing the variants of antigenic peptides referred to as T-cell receptor antagonists. Results of recent experiments with altered peptide ligands compare favorably with T-cell responses predicted by this model.
Animals↗
Evidence for a conformational change in a class II major histocompatibility complex molecule occurring in the same pH range where antigen binding is enhanced.
Many class II histocompatibility complex molecules bind antigenic peptides optimally at low pH, consistent with their exposure to antigen in acidic endosomal compartments. While it has been suggested that a partially unfolded state serves as an intermediate involved in peptide binding, very little evidence for such a state has been obtained. In this report, we show that the murine class II molecule IE becomes increasingly less stable to sodium dodecyl sulfate-induced dissociation since the pH is decreased in the same range that enhances antigenic peptide binding. Furthermore, at mildly acidic pH levels, IEk binds the fluorescent dye 1-anilino-naphthalene-8-sulfonic acid (ANS), a probe for exposed nonpolar sites in proteins, suggesting that protonation produces a molten globule-like state. The association of IEk with a single high-affinity peptide had only a small effect in these two assays, indicating that the changes that occur are distal to the peptide-binding groove. Circular dichroism analysis shows that a pH shift from neutral to mildly acidic pH causes subtle changes in the environment of aromatic residues but does not grossly disrupt the secondary structure of IEk. We propose a model in which perturbations in interdomain contacts outside the peptide-binding domain of IEk occur at acidic pH, producing a partially unfolded state that facilitates optimal antigen binding.
Animals↗
Pathological case of the month. Capillary hemangioma of the lung.
Explore the source record for details and available documents.
Hemangioma, Capillary↗