Biomedical subjects

L S Wilkinson

Publications and source records attributed to L S Wilkinson.

At least 55 records · Page 3Linked to original sources

PubMed1994

The formation of human synovial joint cavities: a possible role for hyaluronan and CD44 in altered interzone cohesion.

During fetal development, cavitation occurs within the primitive skeleton along planes destined to become the articular surfaces of synovial joints. A histochemical study of human fetal limbs was undertaken to identify the cell types involved in this cavitation and the possible role of interactions between cells and extracellular matrix. Cryostat sections were stained with antibodies to CD68, factor VIII related antigen, prolyl hydroxylase, beta 1 integrin, VCAM-1, proliferating cell nuclear antigen, chondroitin-4 sulphate, chondroitin-6-sulphate, hyaluronan synthase and CD44. Similar sections were reacted for uridine diphosphoglucose dehydrogenase (UDPGD) and acid phosphatase activity. Hyaluronan was demonstrated using an aggrecan core protein hyaluronan binding region probe. Macrophages were present prior to cavitation in the periphery of joint interzones but not at the presumptive joint line in the central interzone. Fibroblastic cells were present throughout. Absence of local VCAM-1 expression indicated that cavitation was temporally distinct from full fibroblast-like synoviocyte differentiation. CD44 was expressed by interzone cells at all stages. Staining for hyaluronan and hyaluronan synthase, but not chondroitin sulphates was present in the interzone before and at the time of cavitation. UDPGD activity was increased in a narrow band of cells at the presumptive joint line prior to cavitation. These findings suggest that joint cavitation is dependent on the behaviour of fibroblastic cells and/or adjacent chondrocytes, rather than macrophages. Since UDPGD activity is involved in hyaluronan synthesis, it is proposed that joint cavitation is facilitated by a rise in local hyaluronan concentration in an area of tissue where cohesion is dependent on the interaction between cellular CD44 and extracellular hyaluronan. As proposed by Toole et al. (1984) such a local rise in hyaluronan concentration may lead to a switch from intercellular cohesion to dissociation, leading to tissue cavitation.

Ankle Joint↗

PubMed1994

6-Hydroxydopamine lesions of the prefrontal cortex in monkeys enhance performance on an analog of the Wisconsin Card Sort Test: possible interactions with subcortical dopamine.

The effects of 6-hydroxydopamine lesions of the prefrontal cortex in monkeys were investigated on two cognitive tests of prefrontal function, spatial delayed response, and attentional set shifting. The latter test provided a componential analysis of the Wisconsin Card Sort Test, a commonly used clinical test of frontal lobe function in man. Acquisition of a visual compound discrimination requiring a shift of attention from one dimension to another (extradimensional shift), for example, shapes to lines, was significantly improved. This enhancement was behaviorally specific in that there were no effects on acquisition of a discrimination that required the continued maintenance of an attentional set toward one particular dimension (intradimensional shift), nor any effects on a series of visual or spatial discrimination reversals that involved the repeated shifting of responding between two exemplars from the same dimension. In contrast, spatial delayed response performance was impaired, in agreement with previous results. Neurochemical measures showed a marked depletion of dopamine limited to the prefrontal cortex and a smaller loss of prefrontal noradrenaline. This was accompanied by a long-term adaptive change in the striatum such that extracellular dopamine in the caudate nucleus, as measured by in vivo microdialysis, was elevated in response to potassium stimulation as long as 18 months postsurgery. It is proposed that attentional set shifting is mediated by a balanced interaction between prefrontal and striatal dopamine, and that elevated dopamine contributes to the improvement in attentional set-shifting ability. This interpretation is consistent with the impairment in attentional set-shifting ability observed in patients with Parkinson's disease or with damage to the frontal lobes using the same test as used here for infrahuman primates.

Animals↗

PubMed1993

Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia.

Schizophrenic patients exhibit deficits in the prepulse inhibition of startle, an operational measure of the sensorimotor gating deficits that are theorized to contribute to cognitive disorganization. In rats, the activation of mesolimbic dopamine (DA) disrupts prepulse inhibition, providing a useful model of the similar deficits in sensorimotor gating in schizophrenic patients. Rats reared in isolation exhibit neurochemical and behavioral abnormalities suggestive of hyperactivity in mesolimbic DA systems. In the present studies, rats reared in social groups or in isolation were tested in startle response paradigms using 120 or 105 dB acoustic pulses, some of which were preceded (100 msec) by prepulses that were 2, 4, 8, or 16 dB above the 65 dB background. Isolation-reared animals were hyperreactive only in response to the initial few startle stimuli. The amount of prepulse inhibition was decreased significantly in isolation-reared animals, particularly when midrange 8 dB prepulses were used. A subsequent study replicated the effect of isolation rearing on prepulse inhibition and suggested that the deficit in sensorimotor gating exhibited by isolation-reared animals may be normalized by the administration of the DA antagonist raclopride (0.05 mg/kg). Hence, isolation rearing provides a nonpharmacological way to induce in rats a deficit in sensorimotor gating that is exhibited by schizophrenic patients.

Acoustic Stimulation↗

PubMed1993

Enhancement of amphetamine-induced locomotor activity and dopamine release in nucleus accumbens following excitotoxic lesions of the hippocampus.

This study tested the hypothesis that the hippocampus modulates dopamine-dependent function of the nucleus accumbens using behavioural and neurochemical evidence. Rats with bilateral lesions of the hippocampus induced by colchicine and kainic acid exhibited equivalent levels of spontaneous locomotor activity but a potentiation of the hyperactivity produced, dose-dependently, by D-amphetamine measured in photo-cell activity cages. The same rats subsequently received unilateral implantations of a microdialysis probe aimed at the nucleus accumbens and showed elevated levels of extracellular dopamine in response to D-amphetamine but no significant difference in basal values in comparison with sham-operated controls. The results are discussed in terms of functional interactions between the hippocampus and nucleus accumbens involving the control of mesolimbic dopamine release.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Case report: emphysematous tuberculous pancreatitis diagnosis by ultrasound and computed tomography.

We describe a case of simultaneous tuberculous and pyogenic infection of the pancreas in a 58-year-old Asian man who presented with a pyrexia of unknown origin. There was no evidence of disseminated tuberculosis or immuno-deficiency. The diagnosis was confirmed by ultrasound-guided percutaneous pancreatic aspiration and subsequent progress assessed by sequential computed tomography (CT) and ultrasonography. Complete recovery was achieved on anti-tuberculous chemotherapy without surgical intervention.

Emphysema↗

PubMed1993

Intercellular adhesion molecules in normal synovium.

The vasculature of normal synovium and skin has been examined for the presence of molecules believed to be involved in intercellular adhesion and whose expression on endothelial cells in vitro is known to be upregulated by cytokines. Synovium was obtained from clinically and histologically normal joints removed during amputations for proximal sarcomata. Skin was obtained from healthy volunteers. Cryostat sections of tissues were assessed by immunohistochemistry and microdensitometry for the presence of E-selectin using monoclonal antibody 1.2B6, intercellular adhesion molecule-1 (ICAM-1) using monoclonal antibody 6.5B5 and vascular cell adhesion molecule (VCAM-1) using monoclonal antibody 1.4C3. Both E-selectin and ICAM-1 were present on a proportion of normal synovial venules but at a level comparable to or lower than that found on dermal vessels. (Staining intensities given as mean absorption indices: superficial synovium 1.2B6: 9.9 +/- 11.4, 6.5B5: 10.2 +/- 12.0, deep synovium 1.2B6: 6.6 +/- 9.9, 6.5B5: 24.6 +/- 15.7, skin 1.2B6: 13.1 +/- 16.6, 6.5B5: 36.4 +/- 12.9.) E-selectin expression was most prominent on small superficial venules in synovium and ICAM-1 most strongly expressed on larger, deep venules. VCAM-1 was found at low levels on cells associated with vessel walls but no significant endothelial staining was seen in either type of tissue. VCAM-1 was also present on cells of the synovial lining layer. Some of the findings in synovium could have been attributable to tumour related cytokine release, but the consistency of findings and comparability to skin suggest that this is relatively unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Palisading cells of rheumatoid nodules: comparison with synovial intimal cells.

OBJECTIVES: The palisading cells of rheumatoid nodules share certain features with synovial intimal cells. The similarities between the two cell populations have been reassessed using new cytochemical markers. METHODS: Cell populations in cryostat sections of non-inflamed, rheumatoid and osteoarthritic synovial tissues, and rheumatoid nodules were assessed for the presence of CD68, prolyl hydroxylase, vascular cell adhesion molecule 1 (VCAM-1), and the alpha 4 and beta 1 integrin chains, and the activity of uridine diphosphoglucose dehydrogenase (UDPGD) and nonspecific esterase. RESULTS: Synovial intimal cells formed a dual population of macrophages (nonspecific esterase positive, strongly positive for CD68) and fibroblastic cells (prolyl hydroxylase positive). The latter showed prominent VCAM-1 expression and high UDPGD activity as previously reported and also prominent beta 1 integrin chain expression. Palisading cells similarly proved to be a dual population of macrophages and fibroblastic cells. In contrast with synovial intima, however, the fibroblastic cells lacked UDPGD activity and expression of VCAM-1 and showed no preferential expression of the beta 1 integrin chain. The exception to this rule was where nodules contained central clefts, which were lined with cells showing all the features associated with synovial intimal cells. CONCLUSION: Palisading cells are a mixture of macrophages and fibroblasts, but the latter show no evidence of synoviocyte differentiation. Cells with features of synoviocytes may occur lining clefts within areas of necrobiosis.

Antigens, CD↗

PubMed1993

Vascular cell adhesion molecule 1 and alpha 4 and beta 1 integrins in lymphocyte aggregates in Sjögren's syndrome and rheumatoid arthritis.

OBJECTIVES: Interactions between vascular cell adhesion molecule 1 (VCAM-1) and its ligand, the alpha 4/beta 1 integrin, have been shown to be important in a number of cellular events in vitro. To assess the importance of such interactions in the development of lymphocytic infiltration in diseased tissue the distribution of the two ligands has been studied immunohistochemically. METHODS: Cryostat sections of labial tissue from patients with Sjögren's syndrome, normal labial tissues, rheumatoid synovia, and normal tonsils were stained using antibodies to VCAM-1, alpha 4 and beta 1 integrin chains, and markers for T cells, B cells, macrophages, and follicular dendritic reticulum cells (FDRCs), visualised using alkaline phosphatase and fast red. RESULTS: Staining patterns for VCAM-1 and integrin chains in lymphocyte aggregates in synovial and labial tissues were similar. VCAM-1 staining was found on both vascular and ramifying dendritic cells at the centre of large T cell aggregates and in all aggregates where there was a central clustering of B cells. VCAM-1 colocalised with, but also extended beyond, staining for the FDRC marker R4/23. Staining for the alpha 4 and beta 1 integrin chains was more widespread than staining for VCAM-1, with no significant increase in staining at sites of maximum VCAM-1 staining. In tonsils VCAM-1 and R4/23 codistributed in germinal centres, but staining for the alpha 4 and beta 1 integrin chains was chiefly seen in T lymphocyte areas. CONCLUSIONS: VCAM-1 may be more important in determining the distribution of B than T lymphocytes in lymphocytic infiltration of non-lymphoid tissue. Unlike the follicles of lymphoid tissue, ectopic follicle-like structures in non-lymphoid tissues may form by immigration of B cells via VCAM-1+ vessels at the centre of T cell aggregates.

Arthritis, Rheumatoid↗

PubMed1993

Giant cells in arthritic synovium.

OBJECTIVES: Giant cells are commonly present in inflamed synovium, often in close association with the intimal layer. The nature of these multinucleate cells has been reassessed using new cytochemical and immunochemical techniques. METHODS: Cryostat sections of non-inflamed, rheumatoid arthritic and osteoarthritic synovia were analysed for the presence of CD68 and non-specific esterase, markers associated with macrophages; activity of uridine diphosphoglucose dehydrogenase, associated with fibroblast-like synoviocytes; and tartrate resistant acid phosphatase and the vitronectin receptor subunit CD51, associated with osteoclasts. RESULTS: Giant cells were not seen in non-inflamed tissue. In diseased tissue giant cells in the intimal layer fell into two major groups: CD68 negative or dull cells with high uridine diphosphoglucose dehydrogenase (UDPGD) activity suggestive of true synoviocyte polykaryons; and CD68 positive cells with low UDPGD activity suggestive of macrophage polykaryons. The two groups were seen in samples from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA), but the former were more prominent in OA and the latter in RA. Most CD68 positive giant cells also showed tartrate resistant acid phosphatase activity and prominent expression of CD51. As such they were histochemically indistinguishable from osteoclasts, but their bone resorbing capacity remains unknown. CONCLUSIONS: Giant cells in arthritic synovium appear to be of two types, one related to true synoviocytes and one to macrophages.

Acid Phosphatase↗

PubMed1993

Expression of vascular cell adhesion molecule-1 in normal and inflamed synovium.

BACKGROUND: The intercellular adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) has been implicated in a number of interactions between leukocytes and cells of lymphoid and connective tissue, including endothelial cells. Such interactions within synovial tissue may be important in the pathogenesis of rheumatoid arthritis. EXPERIMENTAL DESIGN: The expression of VCAM-1 on specific cell populations in normal and inflamed synovium was investigated using a range of double-labeling techniques. RESULTS: The strongest VCAM-1 staining was found to be confined to four nonmacrophage populations (as judged in terms of CD68 expression, nonspecific esterase activity, content of prolyl hydroxylase and activity of uridine diphosphoglucose dehydrogenase): (i) type B synoviocytes, (ii) vascular wall cells outside the endothelial layer, (iii) scattered stromal cells with cytoplasmic processes, and (iv) cells resembling follicular dendritic reticulum cells in lymphoid aggregates with germinal centers (in the three samples of rheumatoid arthritic tissue where these were present). Some macrophages of the synovial intima showed weak VCAM-1 staining. Endothelial cell staining was seen but it was consistently weaker than the staining of cells of group ii. CONCLUSIONS: The four cell populations described as showing bright staining for VCAM-1 may all be involved in local interactions with leukocytes of the macrophage or lymphoid series subsequent to initial leukocyte entry into the tissue. Expression of VCAM-1 by these cells may play a role in such interactions.

Arthritis, Rheumatoid↗

PubMed1993

Leukocytes: their role in the etiopathogenesis of skin damage in venous disease.

The role of leukocytes in tissue damage in the liposclerotic skin of venous disease has been investigated. Twenty-eight skin biopsy specimens were obtained from 23 patients with varicose veins of the lower limb, with a spectrum of skin injury ranging from normal to severe liposclerosis. In no patient was a venous ulcer present. Immunohistochemistry was used to determine the cell types present and provide an indication of their activity. The predominant infiltrating cell types present were T lymphocytes and macrophages. B cells and neutrophils were rarely seen. As described previously, the capillaries were greatly increased in number in the papillary dermis and exhibited grossly increased expression of factor VIII-related antigen and major histocompatibility complex class II. Surprisingly, expression of adhesion molecules endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule were not elevated, but intercellular adhesion molecule-1 expression did increase in more severely diseased skin. Perivascular fibrin was seen occasionally, but there was no evidence of microvascular occlusion. Staining for the cytokine tumor necrosis factor-alpha was not increased in liposclerotic skin. Dermal staining for both interleukin (IL)-1 alpha and IL-1 beta was increased in severely liposclerotic skin, but this was not seen at an early stage. Epidermal staining for IL-1 alpha and IL-1 beta was not increased. All changes were confined to the subpapillary region of the skin. These findings demonstrate that accumulation of macrophages and T cells is an event associated with the development of liposclerotic skin changes that may lead to ulceration in venous disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

PubMed1993

Comparison of surface fibroblastic cells in subcutaneous air pouch and synovial lining: differences in uridine diphosphoglucose dehydrogenase activity.

In contrast to synovial tissue, rat subcutaneous air pouch lining was found to lack cells showing high activity of uridine diphosphoglucose dehydrogenase, an enzyme involved in hyaluronan synthesis. This indicates that the properties of cells on the surface of synovium are not determined simply by tissue cavitation. Shearing forces may be more important in inducing the specialized behaviour of synovial surface fibroblasts.

Air↗

PubMed1993

Uridine diphosphoglucose dehydrogenase activity in normal and rheumatoid synovium: the description of a specialized synovial lining cell.

Although synovial lining cells (SLC) have been implicated in the production of hyaluronan (HA), which is found at particularly high concentrations in synovial fluid, the degree to which individual cells within the synovium are adapted to this particular function remains to be elucidated. Uridine diphosphoglucose dehydrogenase (UDPGD) activity is the irreversible, rate-limiting step in the production of UDP-glucuronate, an essential monosaccharide in the synthesis of HA. We have assessed the UDPGD activity, microdensitometrically, in individual lining cells of normal and rheumatoid (RA) synovium, using a modified quantitative cytochemical method. In normal synovium, high activity was confined to the cells of the lining with negligible activity in the deeper subintima. The mean UDPGD activity/cell in lining cells of rheumatoid synovium was significantly lower than the activity in normal SLC. In some samples of RA and normal synovium, a bimodal distribution of cells was evident in the lining on the basis of UDPGD activity, a zone of cells in the basal layers with high UDPGD activity and a separate population of cells in more superficial layers with relatively low UDPGD activity. The results suggest that a particular population of cells is present, consistently in normal and more variably in RA synovial lining, which have high UDPGD activity/cell and may be involved in the production of HA. Furthermore, in RA synovium both the UDPGD activity/cell and the relative proportion of these cells within the lining appear to be decreased.

Arthritis, Rheumatoid↗

PubMed1992

Light microscopic characterization of the fibroblast-like synovial intimal cell (synoviocyte).

OBJECTIVE: To reassess synovial intimal cell populations by light microscopy. METHODS: Non-inflamed, rheumatoid and osteoarthritic synovia were analyzed as tissue sections and cytospin preparations by a series of combined immunohistochemical and cytochemical staining techniques. RESULTS: Two populations of intimal cells were identified. The first carried macrophage markers. The second showed high uridine diphosphoglucose dehydrogenase (UDPGD) activity, minimal cytoplasmic CD68, absent non-specific esterase (NSE) activity, and absent leukocyte and endothelial antigens. The majority of these cells showed a high content of prolyl hydroxylase. CONCLUSION: Combined cytochemical staining for NSE and UDPGD activity allows effective separation of intimal cell populations. We suggest that the cells of high UDPGD activity are the fibroblast-like or type B synovial intimal cells defined by electron microscopy. High UDPGD activity probably reflects a preferential ability to synthesize glycosaminoglycans, including hyaluronan.

Antigens, CD↗

PubMed1992

Olfactory recognition of infants in laboratory mice: role of noradrenergic mechanisms.

Noradrenaline depletion of the olfactory bulbs induces cannibalism at parturition in primiparous mice, without producing anosmia or impairment of maternal behaviour. Similar lesions made in multiparous experienced females do not result in cannibalism. The present studies investigated 1) whether a 30-min exposure to pups or to distal cues from pups given to virgin females before noradrenaline depletion of the olfactory bulbs overcame the impairment in recognition at first parturition, and 2) whether noradrenaline-depleted females allowed to care for their pups for the 24 h following parturition showed a failure in recognition on a second parturition. Experiment 1 showed that exposure to distal cues from pups enabled the females to successfully recognize pups at parturition in comparison to naive females. However, neither the exposure to pup cues nor the fully interactive experience with pups overcame the disruptive effect on recognition at birth of the noradrenaline depletion. In Experiment 2, we found that olfactory recognition was impaired in noradrenaline-depleted females on second parturition, in spite of the mothering experience with their own pups.

Animals↗

PubMed1991

Binding of antibodies raised against tumour necrosis factor alpha (TNF alpha) to blood vessels and macrophages in inflamed synovial tissue.

The distribution of tumour necrosis factor alpha (TNF alpha) in rheumatoid synovium has been investigated. Ten rheumatoid synovia were compared with seven normal synovia and a range of other tissues, using one polyclonal and six monoclonal antibodies. A common staining pattern was obtained with five reagents. Absence of staining of tissue with the other reagents may relate to binding to different epitopes. Excluding cross-reactivity with smooth muscle seen with two reagents, results with the first five reagents were as follows. Normal tissues showed either no staining or faint staining of venular endothelium. In addition skin keratinocytes and colonic mucus showed staining. Rheumatoid synovium showed staining of venules and weaker staining of mononuclear cells, both as individual cells in the deep tissue and more uniformly in areas of the lining layer. The majority of cells that stained for TNF alpha double-stained for CD68 (macrophages). These represented less than 10% of CD68-positive cells. Isolated cells staining for TNF alpha stained for CD3 (T-cells), forming less than 1% of the total T-cells. The presence of staining of venular endothelium suggests that the cytokine may be synthesised by endothelial cells or may be taken up after production by macrophages.

Adult↗

PubMed1991

Demonstration of lymphatics in human synovial tissue.

Using a cocktail of monoclonal antibodies PAL-E and DE-U-10 (anti-desmin), combined in double labelling techniques with the lectin Ulex europaeus agglutinin I (UEAI), vessels consistent with lymphatics were demonstrated in normal human synovial tissue. These vessels were negative for the monoclonal cocktail and positive for UEAI, were thin-walled and were located close to deep arterioles and venules as expected. Elastin was not found to assist identification of lymphatics in synovium. In rheumatoid arthritic synovium no vessels staining in the manner of normal lymphatics were found. This may indicate absence or change of phenotype of this type of endothelium in disease.

Adolescent↗

PubMed1991

Dissociable effects on spatial maze and passive avoidance acquisition and retention following AMPA- and ibotenic acid-induced excitotoxic lesions of the basal forebrain in rats: differential dependence on cholinergic neuronal loss.

Excitotoxic lesions of the basal forebrain were made by infusing either alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or ibotenic acid. Acquisition and performance of spatial learning in the Morris water maze, over a ten day, two trials per day, training regimen were unaffected by the AMPA-induced lesions which reduced cortical choline acetyltransferase activity by 70%. However, acquisition was significantly impaired in rats with ibotenic acid-induced lesions that reduced cortical choline acetyltransferase by 50%. Additionally, ibotenic acid-lesioned rats swam further than either sham or AMPA-lesioned rats, in the "training" quadrant during a probe trial, in which the escape platform was removed, suggesting a perseverative search strategy. Lesions induced with AMPA, but not ibotenate, significantly impaired the acquisition of "step-through" passive avoidance. Both AMPA- and ibotenate-induced lesions significantly impaired the 96 h retention of passive avoidance, but the effect of AMPA was greater on latency measures. Histological analysis revealed that AMPA infusions destroyed more choline acetyltransferase-immunoreactive neurons than did ibotenate infusions but, unlike ibotenate, spared the overlying dorsal pallidum and also parvocellular, non-choline acetyltransferase-immunoreactive neurons in the ventral pallidal/substantia innominata region of the basal forebrain. The impairment in acquisition of the water maze following ibotenate-induced basal forebrain lesions therefore appears unrelated to damage to cholinergic neurons of the nucleus basalis of Meynert and to depend instead on damage to pallidal and other neurons in this area. The AMPA- and perhaps also the ibotenate-induced impairment in the retention of passive avoidance appears to be more directly related to destruction of cholinergic neurons of the nucleus basalis. These data are discussed in the context of cortical cholinergic involvement in mnemonic processes.

Animals↗