Biomedical subjects

A D Wagner

Publications and source records attributed to A D Wagner.

11 recordsLinked to original sources

PubMed1997

Dissociations between familiarity processes in explicit recognition and implicit perceptual memory.

Dual-process theories of recognition posit that a perceptual familiarity process contributes to both explicit recognition and implicit perceptual memory. This putative single familiarity process has been indexed by inclusion-exclusion, remember-know, and repetition priming measures. The present studies examined whether these measures identify a common familiarity process. Familiarity-based explicit recognition (as indexed by the inclusion-exclusion and the independence remember-know procedures) increased with conceptual processing. In contrast, implicit word-identification priming and familiarity-based word-stem completion (as indexed by inclusion-exclusion) increased with study-test perceptual similarity. These dissociations indicate that familiarity-based explicit recognition may be more sensitive to conceptual than to perceptual processing and is functionally distinct from the perceptual familiarity process mediating implicit perceptual memory.

Adult↗

PubMed1996

Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis.

End organ ischemia, fragmentation of elastic membranes, and aneurysm formation in patients with giant cell vasculitis results from an inflammation destroying the mural layers of large and medium sized arteries. Although the inflammatory infiltrate extends through all layers of the affected blood vessel, the most pronounced changes involve the intima and the internal elastic lamina. Analysis of the functional profile of tissue infiltrating CD68+ cells demonstrates that different subsets of macrophages can be distinguished. TGFbeta1-expressing CD68+ cells coproduce IL-1beta and IL-6, are negative for inducible nitric oxide synthase (iNOS), and exhibit a strong preference for localization in the adventitia. The adventitial homing of TGFbeta1+ CD68+ cells places them in the vicinity of IFN-gamma secreting CD4+ T cells which also accumulate in the exterior layer of the artery. Conversely, iNOS expressing CD68+ cells are negative for TGFbeta and are almost exclusively found in the intimal layer of the inflamed artery. The intimal-medial junction is the preferred site for 72-kD collagenase expressing CD68+ cells. Thus, TGFbeta1-producing macrophages colocalize with activated CD4+ T cells and home to an area of inflammation which is distant from the site of tissue damage but critical in regulating cellular influx, suggesting that TGFbeta1 functions as a proinflammatory mediator in this disease. iNOS- and 72-kD collagenase-producing macrophages accumulate at the center of pathology implying a role of these products in tissue destruction. These data indicate that the microenvironment controls the topographical arrangement as well as the functional commitment of macrophages.

Antigens, CD↗

PubMed1996

Does recoding interfering material improve recall?

In 4 experiments, the authors attempted to replicate an improvement in recall of target memories produced by a post-learning clue enabling participants to reorganize and segregate interfering material, as shown by G. H. Bower and T. Mann (1992). The 1st three experiments studied retroactive interference (RI) in free recall of an initial word list after participants were informed post-learning of a way to categorize a second, interfering list. In each case, the reorganizing clue failed to reduce RI. In the 4th experiment, interference during serial recall of an initial list of letters from a 2nd list was examined. Again, the reorganizing clue given after learning failed to reduce RI. Clearly, if the post-information effect is genuine, then better experimental arrangements will be required to demonstrate it more reliably.

Humans↗

PubMed1996

Interferon-gamma-producing T cells in giant cell vasculitis represent a minority of tissue-infiltrating cells and are located distant from the site of pathology.

Giant cell vasculitis is an arteritis that predominantly affects medium- and large-sized arteries. Genetic risk factors and clonal expansion of selected CD4+ T cell specificities in the vascular lesions support the model that giant cell arteritis is a T-cell-driven disease. Interferon (IFN)-gamma production in the tissue is intimately associated with the formation of the inflammatory infiltrates. Antigens inducing stimulation of T cells are unknown. To provide indirect evidence for the type and the tissue localization of the antigen, we examined CD4+ T cells in the lesions that secrete IFN-gamma. Temporal artery specimens from patients with giant cell arteritis were analyzed bu two-color immunohistochemistry applying antibodies to T cell markers. IFN-gamma, the interleukin-2 receptor alpha-chain (CD25) and talin, a cytoskeletal protein that is reorganized in T cells interacting with antigen-presenting cells. Proliferating cells in the lesions were identified through the expression of the Ki-67 nuclear antigen. More than 90% of tissue-infiltrating IFN-gamma-producing cells were CD4+ CD45RO+. They represented a minute subset (2 to 4%) of tissue-infiltrating T cells. IFN-gamma+ T cells aggregated in the adventitial layer of the inflamed artery where they were either diffusely distributed or arranged in clusters. The majority of IFN-gamma-secreting T cells expressed CD25. IFN-gamma+ T cells included a fraction of cells that had reorganized the cytoskeletal protein talin, indicating an interaction of the T cell receptor and an antigen-presenting cell. A subset of IFN-gamma-expressing T cells was undergoing proliferation in the tissue. IFN-gamma-producing T cells in vasculitic lesions of giant cell arteritis express several markers that identify them as T cells that have recently been stimulated through their antigen-specific receptor. These putatively disease-relevant T cells represent only a very minor fraction of tissue-infiltrating cells. Their preferential accumulation in the adventitia is most compatible with the model that they contact the relevant antigen primarily in this particular region of the artery. Their regulatory function appears to extend into the inner media and intima where pathological changes in giant cell arteritis are most pronounced.

Arteritis↗

PubMed1996

Keratinocyte growth factor is highly overexpressed in inflammatory bowel disease.

Recently we demonstrated an important function of keratinocyte growth factor (KGF) in wound re-epithelialization. As KGF is mitogenic for various epithelial cells, we speculated about a role of KGF in epithelial repair processes of other organs as seen in a variety of inflammatory diseases. Here we demonstrate a strikingly increased expression of KGF in surgical specimens from patients suffering from Crohn's disease and ulcerative colitis. The levels of KGF expression strongly correlated with the degree of inflammation as assessed by histological analysis of adjacent tissue and expression analysis of the pro-inflammatory cytokine interleukin-1 beta. The highest levels of KGF mRNA and protein were found in mesenchymal cells of the lamina propria, particularly in highly inflamed areas. As the KGF receptor is expressed in intestinal epithelial cells, KGF seems to act in a paracrine manner to stimulate proliferation of these cells. These data suggest a crucial role of KGF in epithelial repair after injury caused by inflammatory processes.

Blotting, Western↗

PubMed1995

Functional MRI measurement of language lateralization in Wada-tested patients.

In this study the use of functional MRI (fMRI) for measuring language lateralization non-invasively was examined. The subjects were seven patients with histories of temporal lobe epilepsy who had undergone Wada testing for pre-surgical evaluation. Four patients were left-hemisphere-dominant and three were right-hemisphere-dominant for language. They received fMRI scans while they made semantic or perceptual judgments about visually presented words. Regions of the inferior frontal gyrus (pars triangularis and pars orbitalis) and neighbouring orbital cortex, corresponding to portions of Brodmann areas 45, 46 and 47, exhibited significant increases in activation during semantic relative to perceptual judgments. Lateralization of the increases in activation were consistent with the Wada test assessments of hemispheric language dominance in each of the seven patients. These results suggest that, in addition to providing a tool for investigating human cognitive processes, fMRI has significant clinical potential as a non-invasive measure of language lateralization.

Adult↗

PubMed1995

Systemic monocyte and T-cell activation in a patient with human parvovirus B19 infection.

Infection with human parvovirus B19 induces a biphasic disease. The initial phase has been associated with viremia. During the second phase of the disease, a spectrum of clinical syndromes can manifest, including erythema infectiosum, perinatal complications, and symmetric arthropathy that resembles rheumatoid arthritis. Although investigators have suspected that some of the second-phase symptoms are related to immune complex formation, the pathogenesis of parvovirus B19-induced clinical manifestations is not understood. Herein we describe a 63-year-old woman with malaise, fever, and symmetric polyarthritis who had IgM antibodies specific for parvovirus B19. Messenger RNA (mRNA) specific for interleukin (IL) 1 beta, IL 6, and interferon-gamma (IFN-gamma) was detected by polymerase chain reaction. Transcript concentrations were semiquantified by serial dilution of cells and determination of the minimal number of cells that provided a positive signal. Concentrations of IL 1 beta and IL 6 mRNA in peripheral blood mononuclear cells collected during acute disease were increased by the factor of 32 and 8, respectively. IFN-gamma was detected at a 16-fold increased concentration. Two months later, after the patient had experienced complete recovery, production of monokines and IFN-gamma was almost normalized. These data raise the possibility that acute parvovirus B19 infection is characterized by a widespread and systemic activation of monocytes, T cells, and natural killer cells. The correlation of increased cytokine mRNA levels and clinical symptoms suggests a potential role of proinflammatory monokines and lymphokines in disease manifestations.

Acute Disease↗

PubMed1995

Semantic encoding and retrieval in the left inferior prefrontal cortex: a functional MRI study of task difficulty and process specificity.

Prefrontal cortical function was examined during semantic encoding and repetition priming using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing regional changes in blood oxygenation, a correlate of neural activity. Words studied in a semantic (deep) encoding condition were better remembered than words studied in both easier and more difficult nonsemantic (shallow) encoding conditions, with difficulty indexed by response time. The left inferior prefrontal cortex (LIPC) (Brodmann's areas 45, 46, 47) showed increased activation during semantic encoding relative to nonsemantic encoding regardless of the relative difficulty of the nonsemantic encoding task. Therefore, LIPC activation appears to be related to semantic encoding and not task difficulty. Semantic encoding decisions are performed faster the second time words are presented. This represents semantic repetition priming, a facilitation in semantic processing for previously encoded words that is not dependent on intentional recollection. The same LIPC area activated during semantic encoding showed decreased activation during repeated semantic encoding relative to initial semantic encoding of the same words. This decrease in activation during repeated encoding was process specific; it occurred when words were semantically reprocessed but not when words were nonsemantically reprocessed. The results were apparent in both individual and averaged functional maps. These findings suggest that the LIPC is part of a semantic executive system that contributes to the on-line retrieval of semantic information.

Adolescent↗

PubMed1994

Functional profile of tissue-infiltrating and circulating CD68+ cells in giant cell arteritis. Evidence for two components of the disease.

Macrophages represent a critical component in the inflammatory lesions of giant cell arteritis. By combining immunohistochemistry and in situ hybridization, we have analyzed the functional heterogeneity of tissue-infiltrating macrophages in patients with untreated vasculitis. 20% of macrophages in temporal artery tissue synthesized IL-6-specific mRNA and produced IL-6 and IL-1 beta proteins. IL-6 and IL-1 beta production was not limited to CD68+ cells in the lymphoid aggregates but was a feature of CD68+ cells dispersed throughout the tissue. 50% of tissue-infiltrating CD68+ cells synthesized 72-kD type IV collagenase. Only a small subset of CD68+ cells produced cytokines as well as collagenase, indicating functional specialization or distinct differentiation stages of CD68+ cells in the inflamed tissue. Activation of CD68+ cells was not restricted to tissue-infiltrating cells. Expression of IL-6 and IL-1 beta was found in 60-80% of circulating monocytes of patients with untreated giant cell arteritis, whereas collagenase production was restricted to tissue macrophages. IL-6 and IL-1 beta production by the majority of circulating monocytes was a shared feature of patients with giant cell arteritis and polymyalgia rheumatica but was not found in rheumatoid arthritis. These data suggest that giant cell arteritis has two components of disease, an inflammatory reaction in vessel walls and a systemic activation of monocytes. Systemic monocyte activation can manifest independently without vasculitis as exemplified in patients with polymyalgia rheumatica.

Antigens, CD↗

PubMed1993

Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis.

OBJECTIVE: To explore the role of proinflammatory cytokines in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), two clinically related syndromes characterized by an intense acute-phase reaction. In particular, to determine plasma concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) and to correlate changes in plasma IL-6 levels with clinical symptoms during corticosteroid therapy. METHODS: IL-6 and TNF alpha concentrations were determined in plasma samples from patients with untreated PMR or GCA, and plasma IL-6 levels were monitored in patients receiving long-term therapy (14 months) with corticosteroids. To identify IL-6-producing cells, the polymerase chain reaction was used to detect IL-6 messenger RNA. In vitro production of IL-6 and IL-2 by peripheral blood mononuclear cells (PBMC) from treated and untreated patients was quantified using IL-6- and IL-2-specific bioassay systems. RESULTS: IL-6 concentrations were increased in PMR and GCA patients, whereas TNF alpha concentrations were similar to those in normal donors. Administration of corticosteroids rapidly reduced the levels of circulating IL-6 but did not correct the underlying mechanism inducing the increased IL-6 production. In individual patients, changes in plasma IL-6 levels and clinical manifestations during prolonged therapy were closely correlated. Short-term withdrawal of corticosteroids, even after several months of treatment, was followed by an immediate increase in plasma IL-6 concentrations. To identify the cellular source of plasma IL-6, PBMC from treated and untreated patients with PMR or GCA were analyzed for their ability to secrete IL-6 and the T cell-specific cytokine IL-2. Polyclonal T cell stimulation caused a rapid release of IL-6, which was shown to be derived exclusively from CD14+ cells. CONCLUSION: Increased production of IL-6, but not TNF alpha, is a characteristic finding in patients with PMR or GCA. Corticosteroids rapidly suppress IL-6 production but do not correct the underlying mechanism inducing the increased IL-6 production. The close correlation of plasma IL-6 concentrations with clinical symptoms suggests a direct contribution of this cytokine to the disease manifestations and presents the possibility that monitoring IL-6 levels would be useful in making decisions on adjustment of corticosteroid dosage in individual patients.

Aged↗

PubMedDate not supplied

Planning a community nursing centre.

The poor, elderly, single parents and other vulnerable groups have had limited options in receiving affordable, comprehensive and culturally sensitive care. Today, this gap is being filled by nurse-managed centres in accessible areas offering primary care to communities, particularly the underserved. Below, the planning, development and implementation of one such nursing centre.

Community Health Centers↗