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A Goodall

Publications and source records attributed to A Goodall.

At least 19 recordsLinked to original sources
PubMed2003

Beta-elimination: an unexpected artefact in proteome analysis.

Two persistent myths, ingrained in the electrophoretic literature of the last thirty years, namely carbamylation and deamidation, have been recently dispelled (Herbert et al., J. Proteome Res. 2002, in press). We report here, for the first time, a noxious and unexpected artefact in proteome analysis: beta-elimination (or desulfuration), which results on the loss of an H(2)S group (34 Da) from cysteine (Cys) residues for protein focusing in the alkaline pH region. With such an elimination event, a dehydro alanine residue is generated at the Cys site. In turn, the presence of a double bond in this position elicits lysis of the peptide bond, generating a number of peptides of fairly large size from an intact protein. The first process seems to be favored by the electric field, probably due to the continuous harvesting of the SH(-) anion produced. The only remedy found to this noxious degradation pathway is the reduction and alkylation of all Cys residues prior to their exposure to the electric field. Alkylation appears to substantially reduce both beta-elimination and the subsequent amido bond lysis.

Alkylation↗
PubMed1997

Simple objective criteria for diagnosis of causes of acute diarrhoea on rectal biopsy.

AIM: To identify simple, objective, accurate histological criteria for distinguishing acute infective-type colitis, chronic idiopathic inflammatory bowel disease, and irritable bowel syndrome on rectal biopsy in patients with acute onset diarrhoea at first presentation, one to 10 weeks after onset. METHODS: Cell counts and measurements of mucosal architecture were made on initial rectal biopsies from 18 patients with acute infective-type colitis, 17 patients with first acute presentation of chronic idiopathic inflammatory bowel disease, and 23 patients with irritable bowel syndrome. The data were analysed by ANOVA and discriminant analysis. RESULTS: Lamina propria cells were mainly in the upper third in irritable bowel syndrome patients. Increased lamina propria cellularity, mainly in the middle third, and numbers of crypt intraepithelial neutrophils distinguished acute infective-type colitis from irritable bowel syndrome in 93% of cases. Chronic idiopathic inflammatory bowel disease differed from irritable bowel syndrome and acute infective-type colitis in a decreased number of crypts and altered crypt architecture. Chronic idiopathic inflammatory bowel disease showed higher lamina propria cellularity, especially in the basal third, with an increased number of lamina propria neutrophils. On discriminant analysis, crypt numbers distinguished 86% of the cases of chronic idiopathic inflammatory bowel disease from the other groups. CONCLUSION: At one week or more from onset, acute infective-type colitis is characterised by a superficial increase in lamina propria cellularity, with only a slight increase in the number of polymorphs. At this stage, chronic idiopathic inflammatory bowel disease is characterised by a transmucosal increase in cellularity together with crypt loss and architectural abnormality. Thus, measurement of mucosal architecture establishes simple, accurate, objective criteria for routine biopsy diagnosis of chronic idiopathic inflammatory bowel disease from acute infective-type colitis and irritable bowel syndrome at initial presentation, one to 10 weeks after onset.

Acute Disease↗
PubMed1996

Annexins in the human neuroblastoma SH-SY5Y: demonstration of relocation of annexins II and V to membranes in response to elevation of intracellular calcium by membrane depolarisation and by the calcium ionophore A23187.

The human neuroblastoma SH-SY5Y was found to express annexins I, II, IV, V, and VI by western blot analysis. Calcium-dependent membrane-binding proteins were isolated from SH-SY5Y and analysed by 2-dimensional gel electrophoresis. Proteins with Mr and Pi values similar to those of annexins I, II, III, IV, V, and VI were observed. The identity of annexins II and V was confirmed by western blotting. The membrane association of annexins II and V was studied in cells that had been stimulated to release noradrenaline by K+ depolarisation or by treatment with the ionophore A23187. Annexins II and V were both found to associate with membranes in a manner that was resistant to elution with EGTA and required Triton X-100 for their solubilisation. Homogenisation of cells in calcium-containing buffers also resulted in the formation of EGTA-resistant membrane-associated annexins II and V. The results demonstrate calcium-dependent relocation of annexins II and V to membranes in intact cells and suggest that these annexins bind in a calcium-dependent manner to non-phospholipid components of SH-SY5Y membranes. Examination of cells by immunofluorescence microscopy demonstrated that annexin II was homogeneously associated with the plasma membrane before treatment with ionophore and relocated to discrete patches of staining after treatment. Annexin V was found by immunofluorescence to be present in the cytoplasm and in the nucleus, Stimulation of the cells produced no change in the cytoplasmic staining pattern but resulted in a partial relocation of nuclear annexin V to the periphery of the nucleus. The results argue for a general role for both annexins in calcium signalling at discrete intracellular locations. The results are not consistent with the specific involvement proposed previously for annexin II in membrane fusion at sites of vesicle exocytosis.

Annexin A2↗
PubMed1995

Changes in the cellular distribution of lipocortin-1 (Annexin-1) in C6 glioma cells after exposure to dexamethasone.

Glucocorticoid-induced changes in cellular levels of Lipocortin-1 (LC-1) (Annexin 1) in C6 glioma cells were determined by electrotransfer and immunoblotting techniques. Separate cell protein fractions were prepared to study the influence of the glucocorticoid steroid, dexamethasone, on LC-1 localisation. Cells were grown in steroid-depleted medium and exposed to dexamethasone (10(-8) and 10(-7) M) for 2, 6, and 16 hr. The glucocorticoid-dependent changes in cellular content of LC-1 were both dose- and time-related. Increases above control levels in intracellular and extracellular LC-1 content were detected with the greatest changes occurring at the cell surface. The glucocorticoid-dependent alteration in LC-1 distribution in C6 glioma cells was attenuated by the protein synthesis inhibitor, cycloheximide, indicating the involvement of de novo LC-1 synthesis. The significance of these results is discussed in relation to the current concept that some of the anti-inflammatory effect of glucocorticoids occurs through the action of extracellular LC-1.

Annexin A1↗
PubMed1990

Ulcerative colitis: one disease or two? (Quantitative histological differences between distal and extensive disease).

Cell counts and measurements of mucosal architecture were made on rectal biopsies from nine patients with total colitis, eight with left sided colitis, 15 with distal colitis, and 11 with proctitis. The mean total lamina propria cell count in proctitis and distal colitis approached twice that of extensive left sided and total colitis (p less than 0.001) and in distal proctocolitis the cell numbers are further increased in the chronic over the acute phase. This difference was not explained by age, duration, activity, or treatment. The predominantly increased lymphoid and mononuclear cell infiltrate in distal proctocolitis indicates a different pattern of immune response, suggesting a separate process from extensive colitis or a more intense reaction resulting in localisation of disease.

Adolescent↗
PubMed1989

T-cell and plasma cell populations in coeliac small intestinal mucosa in relation to dermatitis herpetiformis.

Differential lymphocyte and plasma cell counts and measurements of mucosal architecture were studied in small intestinal biopsies from 17 controls and 17 patients with untreated uncomplicated coeliac disease of whom five also had dermatitis herpetiformis. Intraepithelial T-cell and plasma cell counts and measurements of mucosal architecture were not significantly different in the two coeliac groups but both groups differed from the controls. Lamina propria T-cell counts were significantly higher in the patients who also had dermatitis herpetiformis than in uncomplicated coeliac disease, with a significant increase in the Leu 2 (CD8) positive (cytotoxic/suppressor) T-cell subset. This suggests a specific abnormality of T-cell control of immune responsiveness in the pathogenesis of the skin manifestations of dermatitis herpetiformis which is not found in uncomplicated coeliac disease.

Adolescent↗
PubMed1988

What is colitis? Statistical approach to distinguishing clinically important inflammatory change in rectal biopsy specimens.

Measurements of mucosal dimension, architecture, and cell counts in both lamina propria and epithelium were made on rectal biopsy specimens from 20 patients with irritable bowel syndrome ("normal" controls); 54 patients with ulcerative colitis, Crohn's disease, and non-specific proctitis; eight patients with small bowel Crohn's disease; and 34 in whom the rectal biopsy specimen was not diagnostic. Discriminant analysis was applied to multiple variables based on the measurements, and three variables were identified as of high predictive value. The most powerful discriminant was increased lamina propria cellularity in all forms of chronic colitis. The ratios of surface length to mucosal length and of surface epithelial height to crypt epithelial height also emerged as discriminants. Chronic inflammatory bowel disease was distinguished from normal in 95% of cases with a definite pathological diagnosis, and 85% of borderline cases were correctly classified as either normal or inflammatory when judged by the final diagnosis after follow up. This study provides a basis for automated diagnosis of rectal biopsy specimens and provides objectively validated criteria which can also be applied in routine histological diagnosis.

Adult↗
PubMed1986

T-lymphocyte populations in normal and coeliac small intestinal mucosa defined by monoclonal antibodies.

Counts of T-lymphocytes within surface and crypt epithelium and lamina propria of normal and coeliac small intestinal mucosa using an immunoperoxidase method are described and related statistically to changes in mucosal structure determined by quantitative histology. The use of multiple pan-T-lymphocyte and subset antibodies allowed comparison of marker patterns in normal and abnormal mucosa. Total numbers of surface epithelial T-lymphocytes and subtypes were not found to be increased in coeliac disease, but there was an increase in density per unit length of epithelium. Distinctive changes in expression of Leu 1, Leu 2, and Leu 5 by the surface epithelial T-lymphocytes suggest that, although their total numbers are not increased, these cells are not passively crowded but have an active role, possibly as committed cytotoxic lymphocytes. Natural killer cells do not appear to be a major population in normal or coeliac small intestinal mucosa.

Adolescent↗
PubMed1985

Neutralization of hepatitis B virus infectivity by a murine monoclonal antibody: an experimental study in the chimpanzee.

Two study chimpanzees were inoculated intravenously with approximately 1,000 chimpanzee infectious doses of hepatitis B virus (HBV), one with subtype adr and one with subtype ayw, each previously incubated with 0.1 ml of a murine monoclonal antibody (IgG 1(K) class) directed against a single epitope on hepatitis B surface antigen common to most or all HBV. Two control chimpanzees received identical doses of HBV not incubated with the murine anti-HBs. Neither study chimpanzee developed HBV infection during 12 months of follow-up as judged by normal serum aminotransferase activity, normal liver biopsies, and negative serological tests for HBV-associated antigens and antibodies. In contrast, both control chimpanzees became infected by HBV as evidenced by elevated serum aminotransferase activity, liver biopsy changes characteristic of viral hepatitis, and the appearance of hepatitis B surface antigen (HBsAg) in their sera. Both study chimpanzees were shown to be fully susceptible to infection with these same HBV inocula when challenged 15 months after the initial inoculations at a time when passively administered anti-HBs was no longer detectable. Prior to challenge with HBV, one of the two study chimpanzees received a second injection of the same volume of the murine monoclonal anti-HBs. The survival of this anti-HBs in serum was reduced from six weeks (after the initial injection) to approximately two weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Duodenal bulb plasma cells in duodenitis and duodenal ulceration.

Using an immunoperoxidase technique IgA, IgM, IgE and IgG plasma cells were studied in endoscopic duodenal bulb biopsies taken from 14 controls, 25 patients with grade 1 duodenitis (Whitehead classification), 12 patients with grade 2 duodenitis and three with grade 3 duodenitis. The control counts were compared with those in the jejunum and rectum. In addition cell counts were compared in 16 pairs of patients, with and without duodenal ulcer, exactly matched for grade of duodenitis. The control counts were not significantly different from counts in jejunum or rectum except for IgG which were higher in the jejunum (p = 0.03). IgA plasma cell counts were significantly increased in both grade 1 and grade 2 duodenitis compared with controls (p less than 0.05 and p less than 0.01). There was no significant difference for the other plasma cells. All plasma cell counts were decreased in the small group of grade 3 duodenitis compared with the other groups. There was no significant difference between counts in duodenitis whether or not there was associated duodenal ulceration. The isolated IgA plasma cell response of the duodenal bulb mucosa in duodenitis is very different from that of the jejunal mucosa in coeliac disease, and the rectal mucosa in inflammatory bowel disease and bacterial colitis and probably represents the basic response to any mucosal damage.

Cell Count↗
PubMed1985

Defining duodenitis: quantitative histological study of mucosal responses and their correlations.

Biopsies from 56 patients with endoscopically normal duodenal bulbs, duodenitis, or duodenal ulceration were studied for counts of plasma cells, polymorphs, and eosinophils and extent of gastric metaplasia, villous atrophy, and mucosal oedema. A correlation matrix showed that the counts of different types of plasma cells were closely correlated with each other and that there was also a close correlation between the presence of intraepithelial polymorphs, villous atrophy, and gastric metaplasia. Cluster and discriminant analysis indicated that the histological changes could be grouped by their statistical association into three simple categories: normal, which includes many cases incorrectly labelled in some classification systems as mild or chronic duodenitis; histologically defined mild duodenitis, characterised by an appreciable plasma cell response and oedema usually with intraepithelial polymorph infiltration and gastric metaplasia; and severe duodenitis, with an appreciable polymorph response and villous atrophy but decreased plasma cells. Decreased plasma cells may be an important indication of peptic ulceration.

Aged↗
PubMed1984

Hepatitis B virus and host cell membrane antigens on a primary hepatocellular carcinoma cell line.

We have defined some membrane antigens of the cultured hepatocellular carcinoma cell line PLC/PRF/5, which contains the integrated genome of hepatitis B virus. Using fluoresceinated antibodies, we identified HLA Class 1 glycoprotein and HB surface antigen on the membrane. Only in a minority of cells was physical association of these antigens demonstrated by co-capping. The presence of a "division" antigen was indicated by reactivity of the cells with the murine monoclonal antibody OKT9.

Animals↗
PubMed1984

Small intestinal plasma cells in coeliac disease.

Using a modified immunoperoxidase technique to achieve optimum staining and reproducible counts of plasma cells in paraffin embedded tissue, IgA, IgM, IgE, and IgG plasma cells were studied in small bowel biopsies from 20 controls, 23 untreated coeliac patients, 19 treated coeliac patients, and seven patients with Crohn's disease not involving duodenum or jejunum. In controls the ratio of the mean counts for IgA, IgM, IgE, and IgG plasma cells was 2.5:1:1:1 respectively. In patients with untreated coeliac disease, counts of all types of plasma cell were significantly increased approximately two-fold compared with controls although for IgG cells there was considerable overlap. The ratio of the mean plasma cell counts in the untreated coeliac patients was 3.5:1.5:2:1. Counts fell significantly after treatment with a gluten-free diet. There was no significant difference between counts in the controls and the Crohn's disease patients. The changes found in coeliac disease may simply be a non-specific response to mucosal damage. The increases in IgA and IgM plasma cells, however, suggest that the deposits of extracellular IgA and IgM observed in coeliac mucosa are locally produced, and the increase in IgE plasma cells raises the possibility that reaginic type hypersensitivity may be involved in coeliac disease.

Adolescent↗
PubMed1983

Rectal mucosal plasma cells in inflammatory bowel disease.

To achieve optimum staining and reproducible counts of plasma cells in paraffin embedded tissue with the immunoperoxidase technique we have found it essential to obtain a plateau count by titration of antisera for each specimen. This modification was used to study IgA, IgM, IgE, and IgG plasma cells in rectal biopsies from 20 controls, 20 patients with ulcerative proctocolitis, 20 with Crohn's colitis, 20 with non-specific proctitis, 15 with bacterial colitis, and seven with Crohn's disease but no apparent large bowel involvement. Counts were correlated with the characteristic histological features of inflammatory bowel disease. In controls the ratio of the mean counts for IgA, IgM, IgE, and IgG plasma cells was 8:3:3:1. All types of plasma cells were very significantly increased in the patients with ulcerative proctocolitis, Crohn's colitis, and non-specific proctitis and counts correlated with the severity of inflammation. There was no significant difference between the counts in these three groups. All counts tended to be higher in bacterial colitis than in controls, the difference being significant for IgA and IgE. When matched for severity of inflammation there was no significant difference between the counts in bacterial colitis and inflammatory bowel disease. The counts in patients with Crohn's disease but no large bowel involvement were not significantly different from controls. These results suggest that changes in plasma cell counts in inflammatory bowel disease are a non-specific response to mucosal damage, possible by a luminal irritant, and do not differentiate the type of inflammatory bowel disease.

Adult↗
PubMed1982

Genetic and sex-linked factors influencing HBs antigen clearance. I. Nonimmune clearance in inbred strains of mice.

Differences in the clearance values of polyvinylpyrrolidone (KPVP) and HBs antigen (KHBs) were seen in several strains of inbred mice. In addition, in all strains studied KHBs was greater in females than in males, while KPVP was not significantly different in the two sexes. In the strain with the lowest KHBs values, the incidence of HBs antibody formation was lower than in the other strains. These data indicate that genetic and sex-linked factors influence nonimmune clearance of HBs antigen in mice. If similar factors exist in man they may explain some of the variation in clinical manifestation of HBV infection.

Animals↗