Simultaneous observation of extensive air showers and deep-underground muons at the Gran Sasso Laboratory.
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Journal Article↗
Biomedical subjects
J Steele
Publications and source records attributed to J Steele.
Positron emission tomographic scanning demonstrates a presynaptic dopaminergic lesion in Lytico-Bodig. The amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam.
We performed positron emission tomography using 18F-6-fluorodopa on four Guamanians with an amyotrophic lateral sclerosis syndrome, eight Guamanians with parkinsonism, and seven clinically normal Guamanians; the results were compared with those of nine Vancouver control subjects. The Guamanian subjects had all been exposed to similar Chamorro lifestyles. The scans were analyzed using a graphic method that calculates a constant for whole striatal 18F-6-fluorodopa uptake. The parkinsonian subjects all had significantly reduced striatal 18F-6-fluorodopa uptake. The group with amyotrophic lateral sclerosis had significantly reduced uptake that was intermediate between that of the control group and the parkinsonian group. Two Guamanian normal subjects had reduced striatal 18F-6-fluorodopa uptake. The nigrostriatal dopaminergic lesion in Guamanian parkinsonism is similar to that found in idiopathic parkinsonism. The nigrostriatal lesions in the subjects with amyotrophic lateral sclerosis and the Guamanian normal subjects are examples of subclinical neuronal damage demonstrable in living subjects with positron emission tomography.
Adult↗
Stent-aided imaging for osseointegrated implants.
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Dental Implantation, Endosseous↗
The antibody repertoire of early human B cells. I. High frequency of autoreactivity and polyreactivity.
Cord blood and fetal liver B cells were immortalized using Epstein-Barr virus, and IgM antibodies from the resulting lines and clones were examined for their binding to a variety of auto-antigens and micro-organisms by ELISA and fluorescence assays. Auto-antigens tested included Fc of IgG, ssDNA and dsDNA, cardiolipin, histones 1-4, collagens type I and II, thyroglobulin, cytoskeletal components, and a tissue section screen. Of 71 cell lines tested, all but 19 showed some autoreactivity. All 32 fetal liver lines reacted to some self-antigens. In cord blood clones, 16 out of 26 bound to auto-antigens. Many of the clones reacted with more than one auto-antigen and were 'polyreactive'. Some of the cord blood clones bound to extracts of micro-organisms, showing specificity for both endogenous and exogenous antigens. The high frequency of CD5+ B cells in the cord blood (greater than 50%) and fetal liver (greater than 70%) argues for many of these clones being derived from this subset. Therefore, our data support the concept that many 'early' B cells produce polyreactive IgM which can bind to a variety of different auto-antigens and micro-organisms. These IgM antibodies are similar to those described by others as 'natural antibodies'.
Antibody Specificity↗
Agalactosyl IgG in inflammatory bowel disease: correlation with C-reactive protein.
The proportion of oligosaccharide chains on the Fc fragment of IgG which terminate with N-acetylglucosamine (GlcNAc) rather than galactose is increased in rheumatoid arthritis and tuberculosis, and in sera from patients with Crohn's disease, probably because of decreased activity of a galactosyltransferase in B lymphocytes. We have assayed the prevalence of agalactosyl oligosaccharides on IgG in sera from 67 patients with inflammatory bowel disease (32 ulcerative colitis and 35 Crohn's disease). The prevalence of agalactosyl IgG significantly increases in the majority of Crohn's patients (19/35 patients), and correlates with the level of C-reactive protein (r = 0.79), and inversely with the concentration of serum albumin. Sera from ulcerative colitis patients show less frequent (nine of 32) and less marked rises in agalactosyl IgG, and sera with high C-reactive protein values can contain normal levels. Thus in ulcerative colitis no correlation was seen between the two assays. The diseases in which the percentage of agalactosyl IgG is raised (rheumatoid arthritis, tuberculosis, Crohn's disease and some ulcerative colitis) are characterised by simultaneous T cell mediated granulomatous tissue damage, and acute phase responses. Levels are normal in less tissue damaging granulomatous conditions, including sarcoidosis, and leprosy (except during episodes of erythema nodosum leprosum). We suggest therefore that a raised percentage of agalactosyl IgG is a correlate of a particular type of T cell mediated pathology which may be relevant to the pathogenesis of inflammatory bowel disease.
Adolescent↗
Lipids, lipoproteins and apolipoproteins A-I and B and apolipoprotein losses in continuous ambulatory peritoneal dialysis.
Comparison of lipid, lipoprotein and apolipoprotein levels was made between 3 groups: continuous ambulatory peritoneal dialysis patients (n = 5); haemodialysis patients (n = 15) and normals (n = 31). Continuous ambulatory peritoneal dialysis (CAPD) patients showed significantly elevated total cholesterol, low density lipoprotein (LDL)-cholesterol and apolipoprotein B (apo B) levels compared with haemodialysis and normal groups. Both CAPD and haemodialysis (HD) showed reduced levels of high density lipoprotein (HDL)-cholesterol and apolipoprotein A-I (apo A-I). Measurement of apo A-I and apo B in dialysate during a 6 h CAPD session indicated significant losses of apo A-I to dialysate with negligible losses of apo B. Grossly elevated apo B and reduced apo A-I indicates that CAPD patients are at increased risk of coronary heart disease and that their risk is probably greater than for haemodialysis patients.
Apolipoproteins A↗
A transient rise in agalactosyl IgG correlating with free interleukin 2 receptors, during episodes of erythema nodosum leprosum.
The proportion of oligosaccharide chains on the Fc fragment of IgG which terminate with N-acetylglucosamine and not galactose (%GO) has previously been shown to be raised in rheumatoid arthritis (RA), Crohn's disease (CD) and tuberculosis (Tb), but to be normal in sarcoidosis (SA), and in both lepromatous and tuberculoid leprosy. However we have now studied %GO in sequential serum samples collected from lepromatous leprosy patients undergoing episodes of erythema nodosum leprosum (ENL). During ENL %GO is transiently raised, and this rise parallels an increase in circulating interleukin 2 receptors (IL-2R). These findings confirm that changes in T cell function occur during ENL. Moreover it appears that %GO rises when there is, simultaneously, T-cell-mediated tissue damage and an acute phase response (RA, CD, Tb, ENL), but not when there is an acute phase response without major T cell involvement, or chronic T cell activity alone (SA, and tuberculoid leprosy). We suggest therefore that %GO is an indicator of a type of T cell activity with broad immunopathological implications.
Acetylglucosamine↗
The secreted antigens of Mycobacterium tuberculosis and their relationship to those recognized by the available antibodies.
Proteins secreted by strains of Mycobacterium tuberculosis during short-term, zinc-sufficient batch culture were identified in order to define antigens likely to be relevant to the pathogenesis of human disease. [35S]Methionine-labelled proteins in supernatants of 4-7 d cultures were separated by PAGE under both denaturing and non-denaturing conditions, and the position of labelled material was determined. Secreted protein patterns of M. tuberculosis were quite similar to those of Bacillus Calmette-Guérin (BCG) but differed by the absence of the 46 kDa dimeric protein specific to BCG and by the presence in large amounts of a 23 kDa protein which, when denatured, gave 13 kDa subunits. This 13 kDa subunit protein constituted up to 20% of secreted proteins in classical strains of M. tuberculosis of phage type B but was not detected in phage type I strains from South India. This may be relevant to the different pathogenicity of these strains. Western blot analysis showed that antigens defined in supernatants of short-term (3 d) cultures of M. tuberculosis constituted a small subset of those seen in supernatants of organisms cultured for longer periods. One of the secreted proteins has the interesting property of binding to fibronectin. The available monoclonal antibodies and antisera have been used to identify lines on immunoblots corresponding to the secreted/released antigens of M. tuberculosis. The present findings suggest that there are major secreted antigens to which antibodies do not yet appear to have been produced experimentally.
Antibodies, Monoclonal↗
A monoclonal antibody raised by immunising mice with group A streptococci binds to agalactosyl IgG from rheumatoid arthritis.
It was shown recently that the IgG of patients with rheumatoid arthritis tends to lack the terminal galactose normally present on the conserved N-linked oligosaccharide situated on the CH2 domain. This results in the exposure of a terminal N-acetylglucosamine linked beta 1-2 to mannose. It is reported here that mice immunised with the peptidoglycan/polysaccharide complex of group A streptococci can be used as a source of monoclonal antibodies binding to this epitope. It may be significant that the organism responsible for rheumatic fever evokes antibodies binding to an abnormality of IgG found in rheumatoid arthritis.
Acetylglucosamine↗
Specificity of antibodies secreted by hybridomas generated from activated B cells in the mesenteric lymph nodes of patients with inflammatory bowel disease.
Hybridomas have been prepared from active B cells in lymphoid tissue draining lesions of Crohn's disease (CD) and ulcerative colitis (UC), by fusion of fresh mesenteric lymph node suspensions with the murine JK myeloma. Two hundred and fifty nine immunoglobulin secreting hybridomas have been obtained from nine patients. The antibodies have been screened for binding to food antigens, sections of human gut, and bacteria including two unidentified acid fast isolates from CD lymph nodes. Autoantibodies, and antibodies to food antigens implicated by others in the aetiology of CD were rare, comprising 1.2%, and 2.5% respectively. Most donors yielded none of these. Thus neither food antigens nor autoantigens are major antigenic stimuli in nodes draining inflammatory bowel disease. On the other hand between 19% and 83% of supernatants from different donors bound to one or more bacterial genus. The mycobacteria and the CD isolates were amongst the genera to which most antibodies bound, though binding to E coli was more frequent. Significantly more CD than UC derived supernatants bound to BCG. As mycobacteria are not though to be part of the normal bowel flora, the high percentage of hybridomas secreting antibodies which bind to this genus is surprising.
Adult↗
Pulmonary clofazimine crystals in a child with acquired immunodeficiency syndrome and disseminated Mycobacterium avium-intracellulare infection.
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Acquired Immunodeficiency Syndrome↗
A simple new method for using antigens separated by polyacrylamide gel electrophoresis to stimulate lymphocytes in vitro after converting bands cut from Western blots into antigen-bearing particles.
The individual antigenic components present in microgram quantities of complex mixtures can be separated reproducibly by polyacrylamide gel electrophoresis and transferred onto nitrocellulose blots. We report that the ng quantities of antigen present in single lines cut from such Western blots can be used to induce maximal lymphoproliferative responses in 30-60 microtitre wells. In order to achieve this the excised lines of antigen-bearing nitrocellulose sheet must be converted into antigen-bearing particles small enough to be engulfed by macrophages. We describe optimal conditions and discuss the applications of this technique.
Antigens, Bacterial↗
High-performance liquid chromatography of coenzyme A esters formed by transesterification of short-chain acylcarnitines: diagnosis of acidemias by urinary analysis.
A protocol for the identification and estimation of short-chain esters of carnitine is described; it is useful for the diagnosis of acidemias. By this method, carnitine esters in urine are converted to coenzyme A esters enzymatically with carnitine acetyltransferase (CAT): short-chain acylcarnitine + CoA cat in equilibrium short-chain acyl-CoA + carnitine. The coenzyme A esters are separated by high-performance liquid chromatography using a radial compression system with a C8 Radial-Pak cartridge and a mobile phase containing 0.025 M tetraethylammonium phosphate in a linear gradient of 1 to 50% methanol. Coenzyme A esters are quantitated by integrator determination of the area under the 254-nm absorption peaks. Enzymatic conversion approaches 100% for acetyl and propionyl esters except in the presence of high levels of free carnitine, which lowers the proportion of ester as acyl-CoA at equilibrium. However, since acidemia patients produce urine low in free carnitine, this problem is minimized. The method is rapid and simple and identifies propionic, methylmalonic, and isovaleric acidemias.
Acidosis↗
In vitro activity of BMY 28100, a new oral cephalosporin.
BMY 28100, a new oral cephalosporin, demonstrated good in vitro activity against common gram-positive and gram-negative respiratory and urinary tract pathogens. Its activity was shown by microdilution techniques to be generally higher than those of ampicillin, cephalothin and cephalexin, but comparable to those of cefaclor and, except for Haemophilus spp. and Branhamella spp., to amoxicillin/clavulanate.
Bacteria↗
Influence of 1,25-(OH)2 vitamin D3 and gamma interferon on the phenotype of human peripheral blood monocyte-derived macrophages.
The effects of 1,25-dihydroxy vitamin D3 and gamma interferon on the phenotypic changes associated with monocyte maturation in vitro were investigated. Human monocytes separated from peripheral blood mononuclear cell populations by adherence to plastic were cultured for 7 days on glass. Immunocytological analysis was performed on monolayers fixed at various times by using monoclonal antibodies specific for mature macrophages (RFD7), interdigitating (dendritic) cells (RFD1), and class II major histocompatibility complex antigen (RFDR1). Without any addition to the culture medium, proportions of these monocytes (normally RFD1 and RFD7 negative) developed either RFD1 positivity (23%) or RFD7 positivity (49%) over 7 days of culturing. The addition of gamma interferon to these cultures markedly reduced the proportion of RFD7-positive cells (less than 10%) but increased the proportion of RFD1-positive cells (40 to 60%). In contrast, 1,25-dihydroxy vitamin D3 reduced the expression of both RFD1 and RFD7. Both of these effects were dose dependent and required at least 3 days of contact with the cells. The possibility that RFD1- and RFD7-positive cells represent functionally distinct subsets makes these effects of significance in our understanding of the role of these mediators in controlling the immunocompetence of nonlymphoid accessory cell populations and in macrophage-associated antimicrobial activity.
Antibodies, Monoclonal↗
The role of gamma-interferon, vitamin D3 metabolites and tumour necrosis factor in the pathogenesis of tuberculosis.
Endotoxin (LPS)-triggered release of tumour necrosis factor (TNF) from human monocytes is high for the first 3 days in culture, and then falls to a trough between Days 4 and 6. This trough is less deep if the cells are cultured in the presence of indomethacin. If monocytes are cultured in the presence of either recombinant gamma-interferon or 1,25-(OH)2 vitamin D3, their capacity for LPS-triggered TNF release is increased. Live virulent Mycobacterium tuberculosis can substitute for the LPS, and is markedly more effective as a trigger than several strains of BCG prepared in an identical manner. Since secretion of IFN-gamma and conversion of circulating 25-(OH) vitamin D3 to the active dihydroxy metabolite by interferon-activated macrophages probably occur in tuberculosis, we suggest that triggering of TNF release from the resulting activated macrophage populations might explain much of the weight loss and tissue damage that characterize this disease. IFN-gamma does not activate effective anti-mycobacterial mechanisms in human monocytes, so its role in tuberculosis may be immunopathological rather than protective.
Antigens, Bacterial↗
A direct effect of glucocorticoid hormones on the ability of human and murine macrophages to control the growth of M. tuberculosis.
Recombinant murine Gamma interferon (rIFN-gamma) causes powerful inhibition of M. tuberculosis by murine peritoneal macrophages. This inhibition is totally abrogated by glucocorticosteroid hormones. In contrast, glucocorticoids do not oppose the weak inhibition of M. tuberculosis by human macrophages which can be induced with human rIFN-gamma, nor do they reduce the effect in this system of 1,25-(OH)2 vitamin D3. However, glucocorticoid hormones do decrease the baseline inhibition of M. tuberculosis exerted by monocytes from some normal human donors without any preincubation in an activating stimulus. Thus there is a steroid-sensitive anti-mycobacterial mechanism in human macrophages, but IFN-gamma is not the lymphokine which induces it. We suggest that this mechanism may be important for protection and steroid-induced reactivation, and deserves further study. On the other hand, the IFN-gamma and vitamin D3 pathway may be more relevant to immunopathology.
Animals↗
Inhibition of virulent Mycobacterium tuberculosis by murine peritoneal macrophages and human alveolar lavage cells: the effects of lymphokines and recombinant gamma interferon.
Both murine peritoneal macrophages and human alveolar lavage cells inhibited growth of M. tuberculosis in a medium containing 10% foetal calf serum. However, whereas addition of recombinant gamma interferon or crude lymphokine reproducibly activated further strong anti-mycobacterial mechanisms in the murine cells, these stimuli had weak and variable effects on human alveolar cells.
Animals↗