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Biomedical subjects

B D Williams

Publications and source records attributed to B D Williams.

At least 109 records · Page 6Linked to original sources
PubMed1989

Effect of ranitidine on gastroduodenal mucosal damage in patients on long-term non-steroidal anti-inflammatory drugs.

Twenty-four patients taking long-term non-steroidal anti-inflammatory drugs (NSAIDs) were followed in a double-blind placebo-controlled trial to assess the effect of ranitidine 300 and 600 mg daily on upper gastrointestinal mucosal damage and to assess methods of monitoring mucosal damage. Sixteen were given ranitidine and 8 had placebo throughout the study. Comparisons suggested that ranitidine reduced symptoms and endoscopic evidence of mucosal damage. Histological evidence of gastritis was present in only half of those on ranitidine but in all receiving placebo. Erosions and blood loss occurred intermittently during the study but faecal blood losses using 51Cr-labelled red cells failed to identify any difference between groups. Endoscopic observation of erosions and serial biopsies may provide simple, reliable measurements for future studies to assess the effect of therapy in reducing mucosal damage from long-term NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Demonstration of hepatic Fc receptor function in vivo.

We describe an investigation of the Fc-receptor dependent function of the hepatic component of the mononuclear phagocyte system (MPS) in rats. Erythrocytes sensitized with the rat IgG2b monoclonal antibody (JY1/98) were cleared by the liver in decomplemented splenectomized rats. This immune clearance was Fc-receptor dependent since it was effectively inhibited by immune complexes of bovine serum albumin (BSA) and rabbit-anti-BSA antibody formed either in vivo or in vitro. Immune complexes formed with F (ab')2 fragment of the rabbit anti-BSA antibody had no effect. Heat-aggregated human gamma globulin was virtually without any competitive activity in the Fc-mediated clearance system. Immune complexes inhibited the hepatic clearance of antibody-sensitized erythrocytes but did not have a significant effect on the early rapid removal of erythrocytes pre-coated with antibody and complement.

Animals↗
PubMed1988

Carotid sinus hypersensitivity and complete heart block in Reiter's syndrome.

We describe a 42-year-old man with Reiter's syndrome who developed complete heart block only 5 weeks after the onset of his illness. He was also noted to have carotid sinus hypersensitivity and evidence of sinoatrial disease. There were no clinical signs or echocardiographic findings to suggest involvement of the aortic root or aortic valve. His arrhythmias were treated successfully with a physiological pacemaker. The combination of sinoatrial and atrioventricular node disease suggests that the inflammatory process in Reiter's syndrome can produce widespread involvement of the conducting system.

Adult↗
PubMed1988

Inflammatory joint disease: a comparison of liposome scanning, bone scanning, and radiography.

Patients with rheumatoid arthritis, psoriatic arthritis, and osteoarthritis were assessed by clinical evaluation, radiography, and joint scintigraphy using technetium labelled methylene diphosphonate (MDP) and technetium labelled liposomes. Although both scanning techniques were more sensitive than radiographs in detecting joint disease, the liposomes scans were positive only in clinically active inflammatory disease. In patients with rheumatoid arthritis liposome scintigraphy was also able to discriminate between different grades of joint tenderness. In inactive inflammatory polyarthropathies, although the MDP bone scans continued to show increased activity, the liposome scans did not and were therefore a more accurate reflection of the clinical state. The increased uptake in the liposome scans may be due to incorporation of the liposomes into the phagocytic cells of the synovium. This scan may, therefore, by reflecting the activity of cells involved in the disease process, provide a useful way of assessing disease activity and progression.

Arthritis↗
PubMed1988

Complement mediated inhibition of immune precipitation in rheumatoid arthritis: studies on interaction of heat aggregated IgG with IgM rheumatoid factor.

Serum samples from patients with seropositive rheumatoid arthritis contain an inhibitor of complement mediated inhibition of immune precipitation (CMIP). This inhibitory effect can be produced by the addition of either purified monoclonal or polyclonal IgM rheumatoid factor (RF) to human serum. The specificity of the rheumatoid factor influences the degree of inhibition, and when precipitation occurs the rheumatoid factor coprecipitates with the antigen-antibody complex. In rheumatoid sera there was a significant positive correlation between IgM RF concentration and inhibitory activity, though the range of inhibitory activity seen for the same concentration of rheumatoid factor was considerable. Small quantities of heat aggregated IgG (HAGG) had a much greater effect on the measurement in an enzyme linked immunosorbent assay (ELISA) of IgM RF than they did on the inhibitory activity of IgM RF in the CMIP assay. Larger quantities of HAGG initiated complement activation and increased the precipitation of immune complexes. IgM RF reduced the complement activating properties of HAGG by reducing the amount of Clq which bound to the aggregate. The mechanisms by which IgM RF overcomes CMIP in rheumatoid sera may involve its inhibitory effects on the binding of Cl to the antigen-antibody complex.

Antigen-Antibody Complex↗
PubMed1988

In vivo and in vitro evidence of cell recovery from complement attack in rheumatoid synovium.

In the previous article we have demonstrated, by quantifying terminal complement complexes in synovial fluid, that membrane attack complex activation occurs in the joint in rheumatoid arthritis. Here we describe evidence of synoviocyte resistance to complement attack in vivo and in vitro. Gel filtration of terminal complement complex positive synovial fluid on Sepharose 2B revealed two forms of terminal complement complex: one form, eluting coincident with the column void, did not react with antibody to the fluid-phase inhibitor of complement membrane attack, the S-protein, suggesting that it was composed of membrane attack complexes, the other form, eluting in the included volume, did react with the anti-S-protein antibody, suggesting that it was composed of functionally inactive SC5b-9 complexes. The high molecular weight membrane attack complex peak was demonstrated by electron microscopy to be composed of membrane vesicles bearing many lesions having the typical appearance of complement membrane attack complexes. No discernible structures were present in the lower molecular weight peak. The effects of non-lethal complement membrane attack on human synoviocytes in culture were also investigated. Synoviocytes were relatively resistant to killing by autologous complement, end-point lysis of optimally antibody-sensitized cells never exceeding 60% even at a serum dilution of 1:2. At serum dilutions of 1:20 or less, no significant cell killing occurred despite a high degree of membrane attack pathway activation, suggesting the existence of resistance and recovery mechanisms. Non-lethal complement membrane attack stimulated the release of toxic reactive oxygen metabolites from synoviocytes. These, and other reactive species released during non-lethal complement attack in vivo, may play a significant role in the pathogenesis of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1988

Measurement of terminal complement complexes in rheumatoid arthritis.

Though complement activation is recognized as a central event in inflammation in the rheumatoid joint, little attention has been paid to the role of the cytolytic membrane attack complex of complement in the pathogenesis of this disease. The membrane attack complex causes a variety of non-lethal effects in nucleated cells, including stimulation of release of inflammatory mediators, and cell proliferation. Thus in the rheumatoid synovium, non-lethal effects of complement membrane attack may play a major role in disease pathology. In order to investigate this possibility, assays for the detection of terminal complement complexes in biological fluids have been established, and used to demonstrate membrane attack pathway activation in rheumatoid arthritis. Terminal complement complexes were present in increased levels in synovial fluid (mean, 1,334 ng/ml) and plasma (mean, 513 ng/ml) in 20 patients with rheumatoid arthritis when compared with controls (mean, 285 ng/ml and 129 ng/ml respectively). Using an assay specific for the SC5b-9 complex it was demonstrated that the raised levels of terminal complement complexes in rheumatoid synovial fluid consisted of a mixture of inactive SC5b-9 complexes and fluid-phase complement membrane attack complexes.

Arthritis, Rheumatoid↗
PubMed1988

Studies in the rat of antibody-sensitized and N-ethylmaleimide-treated erythrocyte clearance by the liver: effects of immune complex infusion and complement activation.

The function of the hepatic component of the mononuclear phagocyte system (MPS) was investigated in the rat using N-ethylmaleimide (NEM)-treated erythrocytes and erythrocytes sensitized with a rat IgG2a monoclonal antibody (R2/15S) directed against the rat RT1Aa class I antigen. The clearance of the antibody-sensitized erythrocytes was biphasic, with the initial phase being rapid and complement dependent. This clearance was entirely hepatic and could be reduced or prevented by the infusion of cobra venom factor (CVF), complement fragments or small amounts of immune complexes, prepared either at equivalence or 10-fold antigen excess. NEM-treated cells were removed rapidly from the circulation of normal rats (t 1/2 6.2 +/- 0.4 min) and their clearance rate was not influenced by complement depletion. Most of the cells accumulated in the liver, although a small proportion (17%) was removed by the spleen. Immune complexes formed at equivalence or heat-aggregated human gamma globulin (HAGG) delayed the removal of these cells from the circulation, although significantly larger amounts of HAGG were required to do this. Antigen-excess immune complexes had no effect.

Animals↗
PubMed1987

Absence of circulating IgG immune complexes in minor recurrent aphthous ulceration.

A monoclonal rheumatoid factor binding assay has been employed to detect IgG type immune complexes in sera from 21 patients with minor recurrent aphthous ulceration and 31 control subjects. In only one of the ulcer group patients was there a marginal elevation of immune complexes above the normal range, with no statistically significant difference between the patient and control groups. Assays of intrinsic serum rheumatoid factor and serum IgG, IgM and IgA levels also showed no significant differences between patient and control groups, with all mean values falling within the normal ranges.

Adolescent↗
PubMed1987

Synovial accumulation of technetium labelled liposomes in rheumatoid arthritis.

Technetium labelled, negatively charged, unilamellar liposomes were given by intravenous injection to patients with rheumatoid arthritis and the joints scanned 20-22 hours later. Positive scintigraphy was obtained in all six patients with active disease, and, with the exception of the small interphalangeal joints, all clinically involved joints could be visualised.

Arthritis, Rheumatoid↗
PubMed1986

Molecular cloning and expression of flagellar radial spoke and dynein genes of Chlamydomonas.

Several flagellar dynein ATPase and radial spokehead genes have been isolated from a Chlamydomonas genomic expression library in lambda gt11. The library was probed with polyclonal and monoclonal antibodies raised against purified flagellar polypeptides, and recombinant phage giving positive signals were cloned. In vitro translation of mRNAs hybrid-selected by the cloned sequences from whole cell RNA provided confirmation of identity for three of the four clones. Evidence supporting the identification of the fourth, which encodes a dynein heavy chain, was provided by antibody selection; the fusion protein produced by this clone selected heavy chain-specific antibodies from a complex polyclonal antiserum recognizing many dynein determinants. One of the radial spoke sequences isolated here is of particular interest because it encodes the wild-type allele of a locus which was defined previously by temperature-sensitive paralyzed flagella mutation pf-26ts (Huang, B., G. Piperno, Z. Ramanis, and D. J. L. Luck, 1981, J. Cell Biol., 88:80-88). The cloned sequence was used to hybrid-select mRNA from mutant pf-26ts cells, and when translated in vitro, the selected mRNA produced a mutant spokehead polypeptide with an altered electrophoretic mobility. This confirms that the pf-26ts mutation alters the primary structure of a radial spokehead polypeptide. To quantify spokehead and dynein mRNAs during flagellar regeneration, all of the cloned sequences were used as hybridization probes in RNA dot experiments. Levels increased rapidly and coordinately after deflagellation, peaked 3-10-fold above nondeflagellated controls, and then returned to control values within 2 h. This accumulation pattern was similar to that of flagellar alpha-tubulin mRNA.

Adenosine Triphosphatases↗
PubMed1986

Studies in cobra venom factor treated rats of antibody coated erythrocyte clearance by the spleen: differential influence of red blood cell antigen number on the inhibitory effects of immune complexes on Fc dependent clearance.

The splenic component of the mononuclear phagocyte system (MPS) was investigated in decomplemented rats by determining the clearance from the blood of erythrocytes coated with a monoclonal antibody (R3/13). The infusion of immune complexes (IC), prepared at 10-fold antigen excess, at an appropriate time during the erythrocyte clearance produced a significant increase in the T1/2 of the antibody coated cells. Immune complexes formed with the F(ab')2 fragment of the rabbit antibody did not have any significant effect. A positive correlation was seen between the dose of immune complex infused and the degree of inhibition of erythrocyte clearance. The influence of red cell antigen number on the behaviour of erythrocytes sensitized with R3/13 was studied by comparing the clearance of DA and (DA X PVG) F1 erythrocytes. F1 erythrocytes, with only half the number of specific antigens on their surface that bind R3/13 antibody were cleared much more slowly (82 +/- 2.6 min, mean +/- s.e.) by the spleen than the DA erythrocytes (44 +/- 1.5 min P less than 0.001). Both cell suspensions were equally susceptible to inhibition by soluble IC. These studies show that the number of specific antigens on the red cell surface influences the rate at which sensitized cells are removed by splenic macrophage Fc receptors but not their susceptibility to inhibition by IC. Our results draw attention to a major defect in the use of autologous erythrocytes coated with anti-rhesus (D) immunoglobulin to assess macrophage Fc receptor function in man.

Animals↗
PubMed1986

Concealed pulmonary abscess: diagnosis by computed tomography.

During childhood, an acute pneumonia with bulging margins usually reflects an abundant production of exudate. However, an unexplained persistence of an expansile pneumonia following therapy indicates that the infectious process may be isolating itself by forming an abscess. Previous reports emphasize that such abscesses are rarely diagnosed prior to thoracotomy or autopsy. Computed tomography facilitates an earlier disclosure of an abscess or empyema that is producing a persistent but unexplained expanding opacification on plain film.

Adolescent↗
PubMed1986

Studies in the rat of antibody-coated and N-ethylmaleimide-treated erythrocyte clearance by the spleen. I. Effects of in vivo complement activation.

The splenic component of the mononuclear phagocyte system (MPS) was investigated in the rat using N-ethylmaleimide-treated erythrocytes (NEM) and erythrocytes coated with a monoclonal IgG2b antibody (R3/13) directed against the rat RT1Aa major histocompatibility antigen. Both cell suspensions were removed by the spleen, and their clearance times were significantly longer in splenectomized animals. The mean clearance times for the NEM-treated cells in both normal and cobra venom-treated rats were similar (19.1 +/- 1.1 min and 19.0 +/- 1.0 min, respectively) but differences were seen between the clearance of R3/13 antibody-sensitized cells in these two groups (normal rats 38.3 +/- 2.8 min and CVF-treated rats 51.7 +/- 4.2 min, P less than 0.02). Different receptors were also involved in the removal of these cells; in normal animals recognition entailed interaction with complement receptors, whereas in CVF-treated animals this was implemented by Fc receptors. Complement activation prolonged the clearance rates of both R3/13 cells and NEM cells in normal animals, but the effect of complement activation on the clearance of NEM-treated cells was achieved via changes in splenic blood flow. When this was prevented from taking place no effect was seen on the clearance of NEM cells, although the clearance of R3/13 cells was inhibited by the complement fragments generated by complement activation.

Animals↗
PubMed1986

Studies in the rat of antibody-coated and N-ethylmaleimide-treated erythrocyte clearance by the spleen. II. Effects of immune complex infusion.

The effects of immune complex infusion on the clearance of antibody (R3/13)-coated and NEM-treated rat erythrocytes by the splenic component of the rat mononuclear phagocyte system (MPS) were investigated. Equivalence complexes of BSA-anti-BSA produced a significant delay in the clearance of the NEM cells (pre-infusion T1/2 19.7 +/- 3.9 min, post-infusion T1/2 26.5 +/- 3.8 min, mean +/- SE, n = 6, P less than 0.01), but this effect could be abolished by agents that prevented the changes in the splenic blood flow that followed complement activation. The immune complexes formed in 10-fold antigen excess (mean size 15S) did not delay the clearance of the NEM cells. Clearance of R3/13-coated cells was impaired by the infusion of immune complexes prepared at equivalence. 10-fold antigen excess or complexes prepared with F(ab')2 fragments of rabbit anti-BSA antibody. The inhibition of red cell clearance was independent of changes in blood flow, but the degree of inhibition produced did not correlate well with the dose of immune complex injected.

Animals↗