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B Henderson

Publications and source records attributed to B Henderson.

At least 19 recordsLinked to original sources
PubMed1992

Interleukin-1: the principal osteolytic cytokine produced by keratocysts.

Fragments of keratocysts removed at operation were maintained in explant culture and the media were assayed for the biological activity of the potent osteolytic cytokines--interleukin (IL)-1, interleukin (IL)-6 and tumour necrosis factor (TNF). Media were also assayed for their ability to stimulate bone resorption. All six cysts examined released IL-1 and IL-6 bioactivity but TNF bioactivity was unmeasurable. Dialysed cyst media stimulated bone resorption and this could be completely inhibited by a monospecific antibody which neutralized IL-1 alpha and IL-1 beta. Immunohistochemical staining of cryostat sections of keratocysts revealed the presence of IL-1 alpha and IL-6 in cyst epithelial cells but not in other cell types. Sections did not react with antibodies to IL-1 beta or TNF. It is therefore proposed that IL-1 alpha is the major osteolytic cytokine produced by keratocysts and that IL-6 and IL-1 may contribute to keratocyst growth by promoting epithelial cell proliferation and bone resorption, respectively.

Adult↗
PubMed1992

Anti-proliferative and cytotoxic activity of surface-associated material from periodontopathogenic bacteria.

The easily solubilized surface-associated material from three bacterial species associated with periodontal diseases, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Eikenella corrodens, produced dose-dependent inhibition of thymidine incorporation by human fibroblasts, the human monocytic cell line U937 and guinea pig epidermal cells. In contrast, lipopolysaccharides from A. actinomycetemcomitans and P. gingivalis were either inactive or substantially less active over the dose range tested. One of the constituents of surface-associated material from a 'non-leucotoxic' strain of A. actinomycetemcomitans was highly cytotoxic to human peripheral blood polymorphonuclear cells, with 50% killing from less than 1 ng/ml. A constituent of the surface-associated material from P. gingivalis was approximately one log order less active. The lipopolysaccharides from these bacteria were at least three log orders less active in neutrophil killing. These findings add weight to the hypothesis that easily solubilized exopolymers from periodontopathogens play a major part in the pathology of periodontal diseases.

Aggregatibacter actinomycetemcomitans↗
PubMed1992

Visual evoked cortical responses and electroretinograms following implantation of human fetal mesencephalon to the right caudate nucleus in Parkinson's disease.

Pattern electroretinograms and visual evoked cortical responses following flash and checkerboard pattern reversal stimulation were performed in 7 patients with advanced Parkinson's disease before and after implantation of human fetal ventral mesencephalon to the head of the right caudate nucleus. Six to nine months following surgery there was bilateral enhancement of flash-evoked response amplitudes. Electroretinogram measurements were unchanged. Individual increases in amplitude and decreases in latency were seen following pattern stimulation which were not statistically significant. A relationship between change in dyskinesia, and change in checkerboard pattern stimulation amplitude at 2.4 cycles per degree suggests that amplitude effects at this stimulus frequency are mediated via altered dopaminergic receptor status in the grafted hemisphere. This may be relevant to the mechanisms leading to generalised clinical improvements following this grafting technique.

Brain Tissue Transplantation↗
PubMed1992

Therapeutic potential of cytokine manipulation.

Interleukin 1 is just one of a large, growing, collection of potent cytokines that are produced by a variety of cells and have a myriad of overlapping activities. Many of these cytokines have important pathophysiological actions in diseases ranging from rheumatoid arthritis to AIDS. Selective inhibition of the synthesis or of the action of specific cytokines may have therapeutic benefit. In this review, Brian Henderson and Simon Blake discuss the ways in which cytokine function could be manipulated pharmacologically for therapeutic benefit.

Animals↗
PubMed1992

Stimulation of bone collagen and non-collagenous protein synthesis by products of 5- and 12-lipoxygenase: determination by use of a simple quantitative assay.

The influence of 5- and 12-lipoxygenase products on the rate of collagen and non-collagenous protein (NCP) synthesis by murine calvarial explants has been investigated using a new assay based on the resistance of native collagen to degradation by pepsin. The reproducibility and simplicity of this assay allows the quantitative estimation of the rate of bone formation in large numbers of cultures. Hydroxyeicosatetraenoic acids (HETEs) stimulated both the rate of collagen and NCP synthesis with maximal stimulation occurring at 10-100 pM. All leukotrienes stimulated collagen synthesis. LTB4, C4 and D4 showed similar dose-responses with maximal activity occurring at 100 pM. LTE4 was less potent only showing activity at 1-10 nM. Only LTD4 demonstrated the capacity to stimulate NCP synthesis with significant stimulation being seen at 10 nM. The extreme sensitivity of bone collagen and NCP synthesis to lipoxygenase products suggests that these mediators may play a physiological role in bone remodelling.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Microbiochemical analysis of changes in proteoglycan and collagen in joint tissues during the development of antigen-induced arthritis in the rabbit.

Microbiochemical assays of the proteoglycan and collagen content of articular cartilage and synovial lining have been performed on tissue sections taken from rabbits with antigen-induced arthritis. This experimental arthritis is a close analogue of the natural disease-rheumatoid arthritis. Animals were killed at intervals during the first 21 days following induction of arthritis to assess changes in the composition of the extracellular matrices of the synovial lining and articular cartilage during the early development of this experimental lesion. In confirmation of earlier studies these microbiochemical assays revealed a rapid and significant loss of proteoglycan from the articular cartilage. This loss was, however, not uniform but was restricted to the intermediate zone of the cartilage. Over the period studied, there was only a slight loss of proteoglycan from the superficial zone of the cartilage facing the joint cavity. These findings demonstrate that, at least in this model, cartilage proteoglycan loss is not due to the action of proteases present in the synovial fluid. Moreover it suggests that the chondrocytes in the mid-zone of the cartilage are responsive to those signals stimulating proteoglycan breakdown. There was no significant loss of collagen from the cartilage over the time period of this study. The synovial lining from arthritic joints, in contrast, showed a progressive increase in both proteoglycan and collagen.

Animals↗
PubMed1992

Inhibition of bone DNA and collagen production by surface-associated material from bacteria implicated in the pathology of periodontal disease.

Gentle extraction of oral bacteria implicated in the pathogenesis of periodontal disease, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, or Eikenella corrodens, with saline removes the extracellular components while leaving the bacteria intact. This readily-solubilized surface-associated material (SAM) has been demonstrated to significantly inhibit DNA and collagen synthesis by murine calvaria at concentrations as low as 10 ng/ml. DNA and collagen synthesis in isolated calvarial osteoblasts were also inhibited by these SAM preparations with similar dose responses. The inhibitory effect of these bacterial expolymers was blocked by 1 microM indomethacin. The potent inhibitory actions on bone synthesis of the SAM from these bacteria may contribute to the alveolar bone loss found in patients with periodontal disease.

Aggregatibacter actinomycetemcomitans↗
PubMed1991

Inhibition of interleukin-1-induced synovitis and articular cartilage proteoglycan loss in the rabbit knee by recombinant human interleukin-1 receptor antagonist.

Intra-articular injection of interleukin-1 (IL-1) into the knee joints of rabbits produces a synovitis associated with the loss of proteoglycan from the matrix of articular cartilage. This experimental finding supports the hypothesis that IL-1 is a possible mediator of the pathology of inflammatory joint diseases and suggests that antagonism of IL-1 could offer a therapeutic approach to these diseases. It has recently been reported that culture of human monocytes on adherent IgG stimulates these cells to synthesize a specific inhibitor of IL-1 bioactivity (IL-1ra) that acts as a receptor antagonist with lymphocytes and mesenchymal cells. We have now shown that intravenous injection of IL-1ra into rabbits given an intra-articular injection of recombinant IL-1 beta not only inhibits the entry of leukocytes into the synovial lining and joint cavity but blocks the ability of IL-1 to cause loss of proteoglycan from articular cartilage. This ability of IL-1ra to inhibit IL-1-induced arthritis in the rabbit reveals that this protein has appropriate pharmacokinetic and pharmacodynamic properties and further strengthens the belief that it may be a useful therapeutic agent.

Animals↗
PubMed1990

Metalloproteinases and cartilage proteoglycan depletion in chronic arthritis. Comparison of antigen-induced and polycation-induced arthritis.

Chronic monarticular arthritis can be induced in ovalbumin-sensitized rabbits by intraarticular injection of ovalbumin (antigen-induced arthritis) or in naive rabbits by injecting hyaluronic acid mixed with the polycation poly-D-lysine (polycation-induced arthritis). Both models show some points of similarity, including joint swelling, the presence of inflammatory leukocytes and the inflammatory mediator prostaglandin E2, and the kinetics of cartilage proteoglycan loss. However, the assessment of the capacity of synovial lining and articular cartilage to synthesize and secrete neutral metalloproteinases reveals a difference between these models. We found that articular cartilage from the inflamed joints of rabbits with antigen-induced arthritis did not synthesize neutral metalloproteinases, although the synovial lining did. In contrast, both the synovial lining and the articular cartilage from the inflamed joints of rabbits with polycation-induced arthritis synthesized neutral metalloproteinases. These findings suggest that in inflammatory synovitis, different mechanisms can operate to produce damage to the matrix of articular cartilage.

Animals↗
PubMed1990

Pathogenesis of antigen-induced arthritis in mice deficient in neutrophil elastase and cathepsin G.

The contribution of neutrophil-derived elastase and cathepsin G to joint pathology has been examined in immune arthritis in the mouse. Neutrophils from beige mice are genetically deficient in lysosomal elastase and cathepsin G, but have normal levels of the acid hydrolases, beta-glucuronidase, and N-acetyl-beta-glucosaminidase. The development of antigen-induced arthritis in normal mice has been compared with that in beige mice. The pattern of synovitis (both leukocyte accumulation and plasma leakage) were indistinguishable in normal and beige mice. Cartilage proteoglycan depletion was quantified by measuring the decrease in safranin O staining intensity, and this, too, was unaltered in mice lacking elastase and cathepsin G. These results suggest that neutrophil elastase and cathepsin G do not contribute to these aspects of joint pathology in antigen-induced arthritis in the mouse.

Animals↗
PubMed1990

Antigen-induced arthritis in the rabbit: ultrastructural changes at the chondrosynovial junction.

Structural changes at the chondrosynovial junction of the lateral border of the lateral femoral condyle have been studied by electron microscopy in rabbits with antigen-induced arthritis of 6 h-27 days duration. Rapid changes in the collagen fibrils of the extracellular matrix in the synovial lining and articular cartilage were noted. Collagen fibrils with unusually large diameters were observed. Overgrowth of cartilage by inflamed synovium was seen within 3-6 days of induction of arthritis and by day 12 the interface between these two tissues was largely indistinguishable. The synovial pannus at this time was fibrotic and infiltrated with plasma cells, lymphocytes and macrophages. Few polymorphonuclear leucocytes were found in the developing pannus. Macrophages were found with extended processes which enveloped neighbouring cells. Some blood vessels had thickened endothelial cells though lymphocytes were not observed in their vicinity. This study reveals the rapidity with which synovial pannus can develop and suggests that there are a number of mechanisms operating to cause cartilage breakdown in antigen-induced arthritis.

Animals↗
PubMed1990

Effect of dietary crude-protein type on fertilization and embryo quality in dairy cattle.

An experiment was conducted to determine whether balancing dietary crude protein for optimal rumen degradability would improve fertilization rate and quality of ova in lactating dairy cows. Thirty-eight Holstein cows in early lactation were fed 1 of 2 diets formulated to be isocaloric and isonitrogenous, containing 16% crude protein. Diet 1 contained 73% rumen degradable intake protein, whereas diet 2 contained 64% rumen degradable intake protein. The cows were induced to superovulate and were inseminated, and ova were recovered nonsurgically on postbreeding day 7. Ova were counted and classified as fertilized or unfertilized. Fertilized ova were scored as excellent, good, fair, poor, or degenerate. Unfertilized ova and poor and degenerate embryos were considered to be nontransferable ova and excellent, good, and fair embryos were considered to be transferable ova. There were no differences for mean number of fertilized, unfertilized, transferable, or nontransferable ova recovered from cows fed the 2 diets (P greater than 0.10). Mean percentage of fertilized ova recovered from cows was greater (P less than 0.05) in those fed diet 2, compared with diet 1. Mean percentage of transferable ova recovered from cows tended to be greater (P = 0.06) in those fed diet 2, compared with diet 1. More cows failed to yield transferable ova (P less than 0.05) when fed diet 1, compared with diet 2. Fertilization failure or early degeneration of embryos may occur in cows fed excess rumen degradable protein.

Animal Feed↗
PubMed1989

Cartilage proteoglycan depletion in acute and chronic antigen-induced arthritis.

We examined the kinetics of proteoglycan (PG) depletion in rabbits with antigen-induced arthritis. There was a rapid loss of PG from arthritic cartilage, reaching 35-40% at day 7. Thereafter, the rate of PG depletion declined, and by day 42, the maximum loss was 55-60%. The initial loss of PG was accompanied by the appearance of large amounts of sulfated glycosaminoglycans (GAGs) in the joint fluid (measured as total sulfated GAGs by dye binding and as keratan sulfate by radioimmunoassay). However, by day 14, the levels of sulfated GAGs in arthritic joint fluid declined to control levels, even though the cartilage demonstrated a sustained depletion of PG. The cartilage PG degradation observed in antigen-induced arthritis could also be produced in normal animals by a single intraarticular injection of recombinant interleukin-1. The acute loss of cartilage PG occurred independently of neutrophil accumulation, both in the case of antigen-induced arthritis and after injection of interleukin-1.

Animals↗
PubMed1989

Inhibition by neuropeptides of interleukin-1 beta-induced, prostaglandin-independent hyperalgesia.

The cytokine interleukin-1 beta (IL-1 beta) is a potent hyperalgesic agent in the rat whereas IL-1 alpha is relatively inactive (Ferreira et al., 1988). IL-1 beta induced a dose-dependent increase in the sensitivity of rat paws to mechanical stimulation following intra-plantar injection but this effect was not reduced by indomethacin (1.0 mg kg-1, p.o.), at a dose known to inhibit completely prostaglandin synthesis in the rat (Salmon et al., 1983). Prostaglandin (PG)E2 enhanced sensitivity to both mechanical pressure and increased temperature but IL-1 beta enhanced only sensitivity to pressure. These observations indicate that IL-1 beta sensitized pressure-sensitive but not temperature-sensitive sensory neurones, through a prostaglandin-independent mechanism. Hyperalgesia induced by IL-1 beta but not PGE2, was inhibited by the neuropeptide melanocyte-stimulating hormone (alpha MSH) and its analogue [Nle4, D-Phe7] alpha MSH which are known to antagonize IL-1 responses in other systems (Holdeman & Lipton, 1985; Cannon et al., 1986). IL-1 beta-induced hyperalgesia was also reduced by the putative IL-1 beta antagonist Lys-D-Pro-Thr (Ferreira et al., 1988) but alpha MSH and its analogue were 10-50 times more potent.

Animals↗
PubMed1989

Effect of indomethacin on swelling, lymphocyte influx, and cartilage proteoglycan depletion in experimental arthritis.

The effects of indomethacin on antigen induced arthritis in rabbits have been investigated. Arthritis was induced in the knee joints of sensitised rabbits by intra-articular injection of antigen. Swelling of the joints was measured for 14 days after antigen challenge, and groups of animals were killed on days 1, 7, or 14 for collection of synovial fluids and tissues. Indomethacin (1 mg/kg, three times daily) reduced joint swelling and the prostaglandin E2 concentrations in synovial fluid. In addition, indomethacin increased the loss of proteoglycan from articular cartilage and the numbers of lymphocytes in the inflamed synovial lining. These findings suggest that the symptomatic benefits of indomethacin and related drugs in inflammatory arthritis may be achieved at the expense of significant adverse effects on joint tissues.

Animals↗
PubMed1989

Gelatinase (type IV collagenase) immunolocalization in cells and tissues: use of an antiserum to rabbit bone gelatinase that identifies high and low Mr forms.

An antiserum was raised to rabbit bone gelatinase (type IV collagenase). It was shown by immunoblotting to detect both the low Mr (72,000) enzyme produced by connective tissue cells from rabbit, pig, human and mouse, as well as the high Mr (94,000-97,000) enzymes secreted by macrophages and polymorphonuclear leucocytes from these species, and by rabbit chondrocytes and endothelial cells. Crossed immunoblotting, antibody inhibition and deglycosylation studies indicated that the high and low Mr forms of gelatinase are immunologically distinct gene products, although their substrate specificity profiles are identical. The anti-gelatinase antiserum was used to immunolocalize the enzyme. Gelatinase was most efficiently detected in rabbit monocytes and connective tissue cells, but cells derived from the human and pig gave poor immunostaining, although mouse gelatinase stained well. The anti-gelatinase antiserum stained cells of the synovial tissue of rabbits at 14 days after induction of an antigen-induced arthritis, demonstrating its usefulness as a tool to assess the role of this enzyme in degradative events.

Animals↗