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Biomedical subjects

B Henderson

Publications and source records attributed to B Henderson.

At least 109 records · Page 6Linked to original sources
PubMed1995

Virulence factors of Actinobacillus actinomycetemcomitans relevant to the pathogenesis of inflammatory periodontal diseases.

There is strong evidence implicating Actinobacillus actinomycetemcomitans as the causative agent of localised juvenile periodontitis (LJP), a disease characterised by rapid destruction of the tooth-supporting tissues. This organism possesses a large number of virulence factors with a wide range of activities which enable it to colonise the oral cavity, invade periodontal tissues, evade host defences, initiate connective tissue destruction and interfere with tissue repair. Adhesion to epithelial and tooth surfaces is dependent on the presence of surface proteins and structures such as microvesicles and fimbriae. Invasion has been demonstrated in vivo and in vitro although the mechanisms involved are poorly understood. The organism has a number of means of evading host defences which include: (i) inhibiting poloymorphonuclear leukocyte (PMN) chemotaxis; (ii) killing PMNs and monocytes; (iii) producing immunosuppressive factors; (iv) secreting proteases capable of cleaving IgG; and (v) producing Fc-binding proteins. Surface components of A. actinomycetemcomitans are potent stimulators of bone resorption and can induce the release of a range of cytokines which can initiate tissue destruction. A number of surface components can also inhibit the proliferation of fibroblasts and their production of components of the extracellular matrix. Little is known, however, regarding the way in which these factors operate in vivo to produce the pathological features of the disease.

Actinobacillus Infections↗
PubMed1995

Comparison of the osteolytic activity of surface-associated proteins of bacteria implicated in periodontal disease.

OBJECTIVES: To compare the osteolytic activity of surface-associated material (SAM) and lipid A-associated proteins (LAPs) from periodontopathogenic bacteria. MATERIALS AND METHODS: Surface-associated material was extracted from the surface and LAPs from the cell walls of a range of periodontopathic bacteria including Actinobacillus actinomycetemcomitans and Eikenella corrodens. These bacterial fractions were assayed to determine their composition and their capacity to induce bone resorption was determined by use of the neonatal murine calvarial bone resorption assay. RESULTS: The SAMs from E. corrodens and A. actinomycetemcomitans demonstrated bone-resorbing capacity at concentrations as low as 1 ng ml-1 which, given the molecular weights of the active components, is in the picomolar range of activity. In contrast, the SAMs from the other three bacteria were significantly less potent and showed a lower efficacy. The LAPs all showed significant, and similar, capacities to induce bone breakdown. CONCLUSIONS: This is the first demonstration that LAP from periodontopathic bacteria can stimulate bone degradation. The LAPs from diverse bacteria all produced similar levels of bone-resorbing activity. In contrast, the SAM showed significant differences in potency and in efficacy (maximal stimulation). This may mean that in vivo certain periodontopathic bacteria have significantly more bone-resorbing capacity than others and should be therapeutic targets.

Aggregatibacter actinomycetemcomitans↗
PubMed1995

Characterization of an antiproliferative surface-associated protein from Actinobacillus actinomycetemcomitans which can be neutralized by sera from a proportion of patients with localized juvenile periodontitis.

The gentle agitation of suspensions of Actinobacillus actinomycetemcomitans serotype a, b, or c in saline resulted in the release of a proteinaceous surface-associated material (SAM) which produced a dose-dependent inhibition of tritiated thymidine incorporation by the osteoblast-like cell line MG63 in culture. This cell line was sensitive to low concentrations of SAM (50% inhibitory concentration, 200 ng/ml for serotype c). Immunoglobulin G antibodies to constituents of the SAM were found in the blood of patients with localized juvenile periodontitis (LJP). Sera from 9 of 16 patients with LJP significantly neutralized the antiproliferative activity of the SAM, while sera from 15 controls, with no evidence of periodontal disease, were unable to neutralize this activity. Neutralization was not directly related to the patient's antibody titer to the whole SAM. Characterization of the antiproliferative activity in the SAM demonstrated that it was not cytotoxic and was heat and trypsin sensitive. The active component separated in a well-defined peak in anion-exchange high-performance liquid chromatography (HPLC) which, when further analyzed by size exclusion HPLC, revealed a single active peak, which had an apparent molecular mass of approximately 8 kDa. The lipopolysaccharide from A. actinomycetemcomitans was only weakly active. SAM from Porphyromonas gingivalis W50 and Eikenella corrodens NCTC 10596 did not exhibit any antiproliferative activity with this cell line, even at concentrations as high as 10 micrograms/ml. This study has shown that SAM from A. actinomycetemcomitans contains a potent antiproliferative protein whose activity can be neutralized by antibodies in the sera from some patients with LJP.

Adolescent↗
PubMed1995

Antifibrotic action of interleukin-1 receptor antagonist in lapine monoarticular arthritis.

OBJECTIVE: To determine if the administration of interleukin-1 receptor antagonist (IL-1ra) to animals with established antigen induced arthritis had any beneficial effects on the synovitis and cartilage destruction. METHODS: Antigen induced arthritis was induced in New Zealand White rabbits, and after two weeks IL-1ra was administered every six hours over a 72 hour period. Animals were then killed and joint tissues examined for the degree of synovitis, synovial fibrosis, and cartilage damage. RESULTS: The response of the arthritis to the treatment was minor in terms of joint swelling, leucocyte accumulation, or cartilage proteoglycan loss. However, the synovial fibrosis was not only halted by administration of IL-1ra, but reversed. The inflamed synovial linings of IL-1ra treated animals showed a significant loss of synovial collagen content and a reappearance of the synovial fat spaces which are prominent in the normal synovial lining. CONCLUSION: This study shows that IL-1ra has potent antifibrotic activity and suggests the use of this agent for the reversal of the fibroproliferative process which is so important in the pathology of rheumatoid arthritis.

Animals↗
PubMed1995

Spinal meningiomas in women in Los Angeles County: investigation of an etiological hypothesis.

A series of 3 studies explored the hypothesis that the preponderance of spinal meningiomas among postmenopausal women relates to their higher prevalence of spinal osteoporosis: (a) medical records showed that meningiomas in women, unlike other spinal tumors, usually arise in the mid thoracic spine where osteoporotic vertebral fractures predominate; (b) radiographic evidence of osteoporosis was seen commonly with meningiomas but not with other spinal tumors; and (c) age-adjusted multivariate analysis of data from an interview study of 81 women with spinal meningioma and 155 random digit dial controls showed 6 factors related to risk. Four factors were protective: (a) current use (at diagnosis) of estrogen replacement therapy [odds ratio (OR) = 0.2; 95% confidence interval (CI) = 0.1-0.6]; (b) past use of oral contraceptives (P trend < 0.01); (c) past participation in sports (OR = 0.5; CI = 0.2-0.9); and (d) premenopausal status (OR = 0.2; CI = 0.1-0.7). Risk increased among women who had ever smoked cigarettes (OR = 1.7; CI = 0.9-3.1) or had a history of high dose radiography (> 500 mrad exposure to active marrow/examination; includes upper or lower gastrointestinal series and/or cardiac angiography; OR = 2.9, and CI = 1.6-5.3), although no association was seen with prior radiotherapy. Other results that did not support the hypothesis include findings that cases and controls were similar in mean body weight and in the proportion who had postmenopausal fractures or height loss. In conclusion, these studies lend some support to our hypothesis, but other known meningioma risk factors such as ionizing radiation also appear important.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Medical device regulation in Canada: direction for change.

The medical device regulatory programme in Canada was first instituted in 1975. Recently this programme underwent a review. This paper first describes the system of regulations as it has been administered by the Health Protection Branch of the government of Canada. The rationale for the establishment of the Medical Devices Review Committee, its deliberations and report are then discussed. Finally, the paper examines measures currently being taken to implement recommendations that will take the regulatory programme for medical devices in Canada into the twenty-first century.

Canada↗
PubMed1994

Bone resorbing activity of surface-associated material from Actinobacillus actinomycetemcomitans and Eikenella corrodens.

The results of this study demonstrate that saline extracted surface-associated material (SAM) of Actinobacillus actinomycetemcomitans and Eikenella corrodens stimulates bone resorption at picomolar concentrations. Various inhibitors of known osteolytic mediators--indomethacin, interleukin-1 receptor antagonist (IL-1ra) and a neutralising antibody to murine tumour necrosis factor (TNF) alpha--were tested to determine the mechanism of action of these SAMs. Bone resorption induced by SAM from E. corrodens was slightly inhibited by indomethacin and almost completely inhibited by blocking the action of TNF alpha; that from A. actinomycetemcomitans was not significantly affected by either of these inhibitors.

Aggregatibacter actinomycetemcomitans↗
PubMed1994

Biodistribution and PDT efficacy of a ketochlorin photosensitizer as a function of the delivery vehicle.

C8KC is a new ketochlorin photosensitizer that must be formulated with an emulsifier because of its poor water solubility. In this report, we compare properties of Cremophor EL (CRM) and Tween 80 as delivery vehicles for C8KC. Unlike Tween 80, CRM altered the physical properties of both human and mouse plasma lipoproteins, resulting in decreased electrophoretic mobility of the individual lipoproteins along with the formation of a lipoprotein degradation product: a phospholipid fraction of low buoyant density. In human plasma, where there was sufficient low-density lipoprotein (LDL) for a distinction to be made, CRM caused a shift in binding of a ketochlorin from albumin to LDL and the degraded lipoprotein fraction. In mice bearing the RIF tumor, the use of CRM for drug formulation was associated with longer plasma and tissue persistence of C8KC, and enhanced photodynamic therapy (PDT) efficacy. These results indicate the importance of both sensitizer and vehicle as determinants of PDT efficacy.

Animals↗
PubMed1994

Distribution of, and a putative role for, the cell-surface neutral metallo-endopeptidases during mammalian craniofacial development.

Endopeptidase-24.11 (neutral endopeptidase, neprilysin, 'enkephalinase', EC 3.4.24.11) and endopeptidase-24.18 (endopeptidase-2, meprin, EC 3.4.24.18) are cell-surface zinc-dependent metallo-endopeptidases able to cleave a variety of bioactive peptides including growth factors. We report the first study of the cellular and tissue distribution of both enzymes and of the mRNA for NEP during embryonic development in the rat. Endopeptidase-24.11 protein was first detected at E10 in the lining of the gut and, at E12, the enzyme was present on the notochord, medial and lateral nasal processes, otocyst, mesonephros, heart and neuroepithelium. In contrast, at this time endopeptidase-24.18 was present only on the apical surface of the neuroepithelial cells. By E14 and E16, NEP was also detected in a wide range of craniofacial structures, notably the palatal mesenchyme, the choroid plexus, tongue and perichondrium. The distribution of endopeptidase-24.18 at these stages was restricted to the inner ear, the nasal conchae, and ependymal layer of the brain ventricles and the choroid plexus. Although endopeptidase-24.11 had been detectable in the craniofacial vasculature at E12 and E14, this was no longer apparent at E16. Significantly, the distribution of endopeptidase-24.11 mRNA closely matched the immunolocalization of the protein at all stages investigated. In order to explore the functional role of these enzymes, inhibition studies were carried out using two selective inhibitors of endopeptidase-24.11, phosphoramidon and thiorphan. E9.5 and E10.5 embryos exposed to either inhibitor displayed a characteristic, asymmetric abnormality consisting of a spherical swelling, possibly associated with a haematoma, predominantly on the left side of the prosencephalon, and the severity of this defect appeared to be a dose-dependent phenomenon. This study suggests that these enzymes play previously unrecognized roles during mammalian embryonic development.

Animals↗
PubMed1994

Casualties treated during MILCON 92: relevance to training of militia medical personnel.

A brigade field hospital provided the medical support for 2,600 troops during MILCON 92 (Militia Concentration 1992). During the exercise, 6.5% of the military personnel required treatment. Medical illnesses were far more common than traumatic injury. The spectrum of medical and surgical illness treated during militia exercises should be used as a guideline for the education and training of medical personnel.

Animals↗
PubMed1994

The effect of recombinant human interleukin 1 receptor antagonist on the induction phase of antigen induced arthritis in the rabbit.

OBJECTIVE: To determine if systemic administration of human interleukin 1 receptor antagonist (IL-1ra) to rabbits during the induction phase of antigen induced arthritis (AIA) could block inflammation and cartilage proteoglycan loss. METHODS: Recombinant human IL-1ra was administered every 6 h to rabbits beginning 1 h before induction of arthritis. Joint swelling was monitored for 72 h and then animals were killed 6 h after the last dose of IL-1ra. Leukocyte accumulation in the joint space and synovial lining was determined and the proteoglycan content and capacity for synthesis was assessed in the articular cartilage of the control and arthritic joints. RESULTS: Administration of IL-1ra had no detectable effect on the induction of arthritis. Swelling proceeded with a similar time course to untreated AIA animals and at 3 days the cellular infiltrate into synovial fluid (SF) was similarly high, the proteoglycan content of SF was also high and cartilage proteoglycan content was depleted. The biosynthesis of proteoglycan in cartilage was also similarly inhibited. No changes were detected in the cartilage and synovium or SF of the contralateral joints of animals receiving IL-1ra. CONCLUSION: IL-1ra given at a dose shown to block synovitis and proteoglycan loss induced by a bolus injection of recombinant IL-1 in rabbits was unable to inhibit the induction of AIA. Our results suggest that the action of IL-1 is not the major factor responsible for the induction of arthritis in this animal model of inflammatory joint disease.

Animals↗
PubMed1993

Iron regulatory factor expressed from recombinant baculovirus: conversion between the RNA-binding apoprotein and Fe-S cluster containing aconitase.

Iron regulatory factor (IRF) is a cytoplasmic mRNA-binding protein that coordinates post-transcriptionally the expression of several important proteins in iron metabolism. Binding of IRF to iron-responsive elements (IRE) in the 5' untranslated region (UTR) of ferritin and erythroid 5-aminolevulinic acid-synthase mRNAs inhibits their translation, whereas binding to IREs in the 3' UTR of transferrin receptor (TfR) mRNA prevents the degradation of this mRNA. IRF binds RNA strongly after iron deprivation, but is inactive, yet present, under conditions of high cellular iron supply. Recently, IRF was also shown to have aconitase activity indicating the existence of an Fe-S cluster in the protein. In the current study we expressed human IRF in insect cells from recombinant baculovirus and analysed IRE-binding and aconitase activities under various culture conditions. Newly made apoprotein, synthesized in the absence of iron, was fully active in IRE-binding, but showed no aconitase activity. In contrast, IRF made by cells grown in high iron medium bound RNA poorly, but exhibited high aconitase activity with a Km of 9.2 microM for cis-aconitate. Apo-IRF was converted in vitro to active aconitase by Fe-S cluster-generating conditions, and under the same conditions lost its RNA-binding capacity. These results indicate that the two activities are mutually exclusive and controlled through formation of the Fe-S cluster.

Aconitate Hydratase↗