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D G Weir

Publications and source records attributed to D G Weir.

At least 127 records · Page 7Linked to original sources
PubMed1989

Complement activation within the coeliac small intestine is localised to Brunner's glands.

Complement activation may play an important role in the pathogenesis of coeliac disease. In the present study immunohistochemical localisation of C3 and of a neoantigen exposed only on the terminal C5b-9 complement complex has been performed on small intestinal biopsy sections from newly diagnosed untreated coeliac patients, from coeliac patients on long-term gluten-free diet and from disease controls. Levels of C3 were markedly increased in treated coeliac patients compared with controls. Staining of C3 was concentrated subepithelially and within the centre of the lamina propria. No staining was detected at these sites using antibody to the neoantigen, however, strongly suggesting that the increased levels of C3 seen in the coeliac patients was the result of increased extravasation of serum proteins rather than complement activation. Surprisingly, complement activation was detected within the glands of Brunner. Positive staining using anti-C5b-9 neoantigen was found in all coeliac patients, both treated and untreated. Three of the 13 disease controls also showed reactivity with this antibody. This novel finding suggests that Brunner's glands, hitherto largely neglected structures, may play an important role in the development of coeliac disease.

Antigens↗
PubMed1989

Defective suppression in the autologous mixed lymphocyte reaction in patients with Crohn's disease.

T helper and suppressor cell control of autologous immunoglobulin production was measured in 14 patients with Crohn's disease (CD) using autologous B cells or monocytes to stimulate regulatory T-cell activity. A pronounced defect in suppressor cell function was observed in the patient group but not in matched controls irrespective of whether B cells or monocytes were used as the stimulus. This defect was observed for IgG, A and M. This defect was seen both in patients with active disease and with inactive CD suggesting the possibility that a primary regulatory defect might exist in this disease. The patient group displayed normal helper cell function.

Adolescent↗
PubMed1989

Treatment of peptic ulcer disease in the arthritic patient.

Dyspepsia associated with arthritis and non-steroidal anti-inflammatory drugs (NSAIDs) is a common clinical problem. Up to 80% of deaths attributable to peptic ulceration may be associated with NSAID usage. The problem is foremost in the elderly population, in which there has been an increase both in the incidence of peptic ulcers and in the use of NSAIDs. Although the development of duodenal ulceration is not clearly associated with NSAIDs, it is accepted that these drugs increase the risk of gastric ulceration and the occurrence of peptic ulcer complications. Asymptomatic peptic ulceration is common, and patients taking NSAIDs are often asymptomatic prior to presentation with life-threatening complications. The key principle in management of this problem is prevention through careful selection of patients for NSAID use, adequate treatment of peptic ulceration and maintenance of remission. A variety of effective drugs are available for the treatment of peptic ulcers, including H2-receptor antagonists, pirenzepine, sucralfate and colloidal bismuth subcitrate. However, it is recognised that peptic ulceration is a chronic disease with a relapsing-remitting course, often with asymptomatic ulcer episodes. The knowledge that current ulcer-healing strategies do not significantly alter this natural history has lead to increasing efforts to prevent relapse with effective 'maintenance' therapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

The subclass profile and complement activating potential of anti-alpha-gliadin antibodies in coeliac disease.

In a randomly selected group of coeliac patients, alpha-gliadin antibodies (AGA) of subclasses IgG1 and IgG3 were significantly elevated (p less than 0.01) in comparison to both normal and disease control groups. This result was, however, influenced by increased total AGA levels in the coeliac patients. AGA subclass profiles of cohorts of coeliac and normal controls matched for total IgG AGA were therefore compared. It was found that IgG3 AGA levels were higher in the coeliac group (p = 0.006) while IgG4 titres were higher in the control group (p = 0.005). Titres of IgG1 and IgG2 AGA did not differ between the two groups. Because of the marked differences between the ability of IgG3 and IgG4 to activate complement, alpha-gliadin-specific complement fixation was measured. Using randomly selected coeliac and normal sera, the patient group activated highly significantly greater quantities of complement than controls (p less than 0.01). Furthermore, when samples matched for total IgG AGA were compared, sera from coeliac patients were again found to activate greater amounts of complement than sera from controls (p = 0.024). Thus AGA in coeliac sera are both structurally and functionally distinguishable from AGA in normal control sera.

Adolescent↗
PubMed1988

Peptic ulceration.

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Adenosine Triphosphatases↗
PubMed1988

Three computer models for the calculation of prevalence of peptic ulcer disease during long-term treatment.

At present the effects of maintenance treatment for peptic ulcer disease are usually calculated by using 'life-table' analyses. Whilst these accurately demonstrate the speed with which an initial relapse occurs they make no allowance for the fact that, in clinical practice, a relapse often responds to a further course of full-dose treatment and the patient then returns to maintenance therapy. A further compounding factor is that, in any long-term study, patients will be lost to follow-up for a variety of reasons not all related to failure of the treatment. In this paper we describe the use of 'prevalence rates' to better reflect the outcome of peptic ulcer management. Three 'computer models', which have been developed to address the problems of patients leaving the study for any reason during such a long time-period, are also described, as are the underlying assumptions made. Using the results from a long-term study of continuous treatment with cimetidine, the 'prevalence rates' of ulcer disease over 6 years were calculated. Observed relapse rates appeared to fall with time (from 2.7% for duodenal ulcer (DU) and 2.5% for gastric ulcer (GU) to 1% and 2% respectively). However, on applying the models to the data, prevalence rates tended to rise slowly with time for the first 3 years in each of the models tested. At 6 years, two of the models suggested that the prevalence rate for DU would be about 8%; this is not very different to the reported recurrence rate after surgical treatment by truncal vagotomy and pyloroplasty. It is concluded that 'prevalence rates' should be used to assess long-term medical treatments for ulcer disease. Similar methods could also be used to examine the medical treatment of any other disease where multiple relapses, capable of responding to re-treatment, occur. The use of models proved beneficial in compensating for patients lost during the study.

Computer Simulation↗
PubMed1988

Differential expression of HLA-D gene products in the normal and coeliac small bowel.

Monoclonal antibodies to monomorphic determinants of the MHC class II region products, HLA-DR, DP and DQ were used to investigate their expression on cells of the normal and coeliac (both treated and untreated) small bowel. HLA-DR antigens showed a characteristic distribution in the normal small bowel: epithelial cells in the apical portions of the villi stained heavily, and this staining decreased in intensity towards the villous base. The crypt epithelial cells were clearly unstained. Stellate cells within the lamina propria were also HLA-DR positive. HLA-DP antigens showed a similar distribution, although the intensity of staining was less than that seen with HLA-DR. HLA-DQ antigens were absent from epithelial cells and were confined solely to cells within the lamina propria. In untreated coeliac disease, the intensities of both HLA-DR and HLA-DP were increased, and in addition a more extensive distribution of these antigens was observed. In addition to occurring on the surface epithelial cells, DR and DP antigens were now present on crypt epithelial cells. Despite this change in expression of DR and DP antigens, the distribution of HLA-DQ was essentially unaltered from that of the normal small bowel. The findings in treated coeliac disease were intermediate between those in the normal and untreated coeliac small bowel. The differential expression of class II antigens by normal and diseased small bowel epithelium which has been demonstrated may have implications for interactions of these cells with cells of the immune system.

Celiac Disease↗
PubMed1988

Methylation deficiency causes vitamin B12-associated neuropathy in the pig.

Pigs were treated with N2O which is known to impair vitamin B12 function in vivo. Such pigs demonstrated an inability to gain weight, progressive ataxia, and spinal neuropathy. The ataxia was totally and the neuropathy partially preventable by dietary methionine supplementation. Methionine synthase activity was inhibited in both the liver and brain. There was a marked elevation of S-adenosylhomocysteine in the neural tissues and a concomitant failure of S-adenosylmethionine to rise and thus maintain the methylation ratio, except when supplementary dietary methionine was added. In contrast, the methylation ratio in the rat was affected to a lesser extent. The neuropathy, it is suggested, is caused by raised S-adenosylhomocysteine levels in neural tissue; as a result, the methylation ratio is inverted and S-adenosylmethionine-dependent methylation reactions are inhibited.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1988

Studies on the interaction between alpha-gliadin and HLA and T cell receptor molecules in coeliac disease.

Coeliac disease has a known strong linkage with the HLA complex and has also recently been linked to the T cell receptor genes but the mechanism whereby these genes confer susceptibility is not known. This study has examined two possible mechanisms: (i) direct, lectin-like binding of alpha-gliadin (the causative agent of CD) to HLA or TcR molecules and (ii) antigenic cross-reactivity between alpha-gliadin and HLA or TcR molecules. A flow cytometer was used to assess interactions between alpha-gliadin, anti-alpha-gliadin antibodies (raised in both coeliac patients and in rabbits) and EBV-transformed B cell lines from coeliac patients and HLA-matched and mismatched normal controls. The B cell lines were shown to express HLA-DP, -DQ and -DR antigens which are also found on coeliac intestinal epithelial cells. After incubating B cell lines with alpha-gliadin over a wide range of concentrations, no binding of alpha-gliadin to any of the cell lines could be detected with either of the gliadin-specific antibodies. This suggests that HLA molecules do not bind to alpha-gliadin in a lectin-like fashion. In contrast to the B cell lines, alpha-gliadin binding to peripheral blood monocytes could be demonstrated. This binding occurred equally to patient and control monocytes and was not influenced by HLA allotype. The second possibility tested was that alpha-gliadin and the disease-associated HLA molecule bear antigenic similarities. However, neither rabbit anti-gliadin serum nor purified human alpha-gliadin antibody bound directly to the B cell lines. Using peripheral blood T cells similar results were obtained; no binding of alpha-gliadin or antibodies to alpha-gliadin was found. Thus this study shows that the HLA and TcR associations with CD are not explained by the direct binding of alpha-gliadin to these molecules nor by a sharing of antigenic determinants between alpha-gliadin and these molecules.

B-Lymphocytes↗
PubMed1987

Removal of endogenous peroxidase activity from cryostat sections for immunoperoxidase visualisation of monoclonal antibodies.

The interpretation of immunoperoxidase staining of frozen tissue sections can be severely limited by the presence of endogenous peroxidase enzymes in the tissue. Previously recommended methods of reducing this enzyme activity were examined, but were found to be unsatisfactory when applied to the small intestine. A method, which effectively eliminates this background staining but which does not interfere with the binding of monoclonal antibodies to various tissue components, is described. This method may prove useful in immunoperoxidase studies of other tissues in which high levels of endogenous peroxidase are present.

Antibodies, Monoclonal↗
PubMed1987

Humoral response to alpha gliadin as serological screening test for coeliac disease.

The diagnostic value of measuring alpha gliadin antibodies in children with suspected coeliac disease has been evaluated prospectively. Jejunal biopsy and alpha gliadin antibody measurements were performed in 77 consecutive children who were being investigated for a suspected malabsorption syndrome. The typical small intestinal histological lesion of coeliac disease was found, and this diagnosis was subsequently confirmed clinically in 20 children. Raised IgG alpha gliadin antibody concentrations were found in 19 (95%). Fifty of 57 patients (88%) with a normal jejunal mucosa had normal alpha gliadin antibody concentrations. These results are similar to those previously reported in a prospective study of adult patients with coeliac disease and indicate that measurement of alpha gliadin antibody is a highly sensitive and specific screening test for childhood coeliac disease.

Adolescent↗
PubMed1987

An epidemic of pseudomembranous colitis: importance of person to person spread.

Twenty three cases of pseudomembranous colitis (PMC) occurred in three hospitals in 10 months. Retrospective analysis shows that they represented a single epidemic with a readily traceable chain of person-to-person contact within and between hospitals. Most patients had severe pre-existing illness and all had broad spectrum antibiotics, including either ampicillin/amoxycillin, a broad spectrum cephalosporin (particularly cefotaxime), or both. All patients had severe diarrhoea and all responded to vancomycin, but relapse occurred in five. Ten patients eventually died, principally because of underlying disease rather than from PMC. Failure to find fibrin thrombi in blood vessels in biopsies and the scanty distribution of non-invasive bacteria supports the concept of mucosal damage by bacterial toxin, rather than by direct infection, or ischaemia. Although environmental colonisation cannot be excluded, the observed pattern of spread suggests a major role for direct person-to-person crossinfection in the spread of disease in this outbreak.

Aged↗
PubMed1987

Combined anti-muscarinic and H2 receptor blockade in the healing of refractory duodenal ulcer. A double blind study.

The purpose of this study was to determine if pirenzepine and cimetidine given together was superior to cimetidine alone in inducing healing of refractory duodenal ulcers which remained unhealed after treatment with cimetidine or ranitidine for at least eight weeks. One hundred and thirty one patients from six centres were randomised to receive either cimetidine (C) 800 mg daily or cimetidine 800 mg plus pirenzepine (C + P) 100 mg daily under double blind conditions for six weeks. The healing rate was similar in both groups, irrespective of the method of calculation. On an intent-to-treat analysis, healing was: C 66%, C + P 57%, and amongst the patients who completed treatment, healing was 70% in both groups. Patients on C and on C + P experienced a similar decrease in daytime and in night time pain. Side effects of treatment, notably dry mouth and blurred vision, were reported more often by patients on combination therapy. Combined treatment with cimetidine plus pirenzepine in patients with refractory duodenal ulcer is unlikely to be beneficial.

Adult↗
PubMed1987

Histological changes associated with wheat protein antibodies in the absence of villous atrophy.

A retrospective study was conducted to assess the association of alpha-gliadin antibodies with intraepithelial lymphocyte counts. Twelve subjects with apparently normal small intestinal histology and raised alpha-gliadin antibody titres had significantly increased intraepithelial lymphocyte counts (42 (SEM) 5.9) when compared with 16 subjects with normal alpha-gliadin antibody titres (17 (3.2); p less than 0.001). These findings show that in the absence of gross pathology raised alpha-gliadin antibody titres are associated with increased numbers of intraepithelial lymphocytes and may reflect continuous immunological processes in the small intestine.

Antibodies↗
PubMed1987

Immunoperoxidase demonstration of the cellular composition of the normal and coeliac small bowel.

Immunohistological analysis of the cellular composition of the small intestinal mucosa in a group of untreated and treated coeliac patients and non-coeliac control subjects was performed using monoclonal antibodies and an immunoperoxidase technique. A characteristic cellular distribution was observed within the normal mucosa. The intraepithelial and lamina propria compartments were occupied mainly by T suppressor/cytotoxic and T helper/inducer cells respectively. Further subdivision of lamina propria T helper/inducer cells with the Leu 8 antibody revealed that these were of the Leu 3a+ Leu 8- phenotype. Macrophages, defined by the RFD7 antibody, were seen to occupy the same microenvironment as T helper/inducer cells. T cells expressing the T cell activation antigen defined by anti-Ta1 were found with the normal lamina propria, although few cells were identified by the anti-Tac antibody. HLA-Dr antigens were expressed by stellate cells within the lamina propria, and also by the epithelial cells of the villi, but not by normal crypt epithelial cells. In untreated coeliac patients the distribution of the various cell types was essentially unchanged, although the number of these cells was markedly increased, including those which expressed the Ta1 antigen. A significant deviation from normal in the expression of HLA-DR antigens was found in the coeliac small bowel: these antigens were expressed not only on the villous epithelial cells but also on the epithelial cells of the crypts. Immunohistological findings in the treated coeliac patients were intermediate between the normal and untreated coeliac groups, and were completely normal in those patients with complete histological resolution of their disease. These results suggest that coeliac disease is accompanied by an enhanced stimulation of the normal mucosal immune response and do not imply a primary pathogenic role for the immune system in this disease.

Antigens, Surface↗