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Biomedical subjects

B B Scott

Publications and source records attributed to B B Scott.

At least 19 recordsLinked to original sources
PubMed2000

Differential levels of granzyme B, regulatory cytokines, and apoptosis in Crohn's disease and ulcerative colitis at first presentation.

The mechanisms of tissue damage in ulcerative colitis and Crohn's disease may reflect disordered humoral or cell-mediated effector mechanisms, respectively. Mucosal biopsies from untreated inflammatory bowel disease patients and normal controls were analysed for the expression of granzyme B, a cytotoxic effector molecule specifically associated with cell-mediated immunity, and for regulatory cytokines. Messenger RNA (mRNA) was analysed by reverse transcription-polymerase chain reaction and enzyme-linked oligonucleotide chemiluminescence assay. Mucosal biopsies were analysed by immunohistochemistry for granzyme B protein and lymphocyte markers and for the presence of apoptotic cells by terminal deoxynucleotidyl transferase end labelling. Granzyme B mRNA was elevated in Crohn's disease, but not in ulcerative colitis or control mucosal biopsies. Granzyme B mRNA levels correlated with interferon gamma mRNA levels in Crohn's disease. Granzyme B was expressed in CD3+, CD8+ T cells in the lamina propria of Crohn's disease mucosa and there were significantly more apoptotic cells in the lamina propria in Crohn's disease. In conclusion, granzyme B-expressing T lymphocytes are present in the focal mucosal lesions of Crohn's disease, together with spatially related apoptotic cell death. These results support the hypothesis that T-cell-mediated cytotoxic effector mechanisms may play a role in Crohn's disease.

Adolescent↗
PubMed1998

The putative 116 kDa osteoclast specific vacuolar proton pump subunit has ubiquitous tissue distribution.

The pharmacological profile of the osteoclast proton pump has been demonstrated to be unique and to be the most active of all acid transport systems thus far studied. The recently reported putative 116 kDa osteoclast specific vacuolar proton pump subunit could possibly explain the unique nature of this proton pump. Here, we demonstrate however, that the osteoclast 116 kDa subunit is not osteoclast specific but has ubiquitous expression in human tissue.

Base Sequence↗
PubMed1998

Bismuth-containing single-antibiotic 1-week triple therapy for Helicobacter pylori eradication.

BACKGROUND: Although bismuth was both the first drug shown to alter the natural history of peptic ulcer disease and also a constituent of the first very effective eradication regimens, it has been excluded from the newer regimens, despite its safety and low cost, in favour of two antibiotics. AIM: To asses a novel 1-week regimen consisting of bismuth, clarithromycin and a proton pump inhibitor in routine clinical practice. METHODS: One hundred and three consecutive patients with peptic ulcer disease and antral biopsies containing Helicobacter pylori were given a 7-day course of treatment with bismuth (tripotassium dicitrato bismuthate chelate) 120 mg q.d.s., clarithromycin 500 mg t.d.s. and lansoprazole 30 mg o.d. Completeness of eradication was assessed by a l3C-urea breath test, in all except three patients, at least 4 months later. RESULTS: Of the 100 patients who were assessed in this open treatment study 84 (84%; 95% CI: 77-91%) had a negative breath test. Minor side-effects were reported by 14% and more troublesome side-effects (nausea, vomiting, diarrhoea, hallucinations, nasty taste and body pains) were reported by 10%. CONCLUSIONS: A 1-week course of triple therapy including bismuth, clarithromycin and a proton pump inhibitor is effective in routine clinical practice and is well tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

A strategy for osteoporosis in gastroenterology.

Osteoporotic fractures are a major public health problem. Gastroenterologists see many patients at risk of osteoporosis, particularly those with coeliac disease and inflammatory bowel disease. In this paper, the extent of the problem is reviewed and a strategy of investigation and treatment is recommended.

Absorptiometry, Photon↗
PubMed1997

Interleukin-8 and inducible nitric oxide synthase mRNA levels in inflammatory bowel disease at first presentation.

Interleukin-8 (IL-8) and nitric oxide (NO) may be important mediators in the pathogenesis of chronic idiopathic inflammatory bowel disease (CIIBD), but their roles in disease activity in ulcerative colitis (UC) and Crohn's disease (CD) are uncertain. The aim of this study was to measure mRNA for IL-8 and inducible NO synthase (iNOS) in small mucosal biopsies from untreated patients at first presentation and to relate these measurements to the histological levels of polymorph infiltration graded on a ten-point scale. For this purpose, a sensitive enzyme-linked oligonucleotide chemiluminescent assay (ELOCA) was developed to quantitate reverse transcription-polymerase chain reaction (RT-PCR) products amplified from RNA from paired biopsy samples. The levels of IL-8 and iNOS mRNAs were calculated as ratios of the RT-PCR products to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RT-PCR product. In UC patients, median values of IL-8/GAPDH and iNOS/GAPDH were significantly elevated compared with controls and CD. However, in both UC and CD, the IL-8/GAPDH and iNOS/GAPDH ratios correlated significantly with polymorph infiltration. ELOCA enabled quantitation of multiple mRNAs in small mucosal biopsies from untreated patients with CIIBD and supported a role for IL-8 and iNOS in acute inflammation in both UC and CD.

Adult↗
PubMed1997

Rheumatoid arthritis synovial fibroblast and U937 macrophage/monocyte cell line interaction in cartilage degradation.

OBJECTIVE: To examine the interaction between synovial fibroblasts and macrophages in the context of cartilage degradation. METHODS: An in vitro model of human cartilage degradation was used, in which purified populations of fibroblasts and macrophages were added to a radiolabeled cartilage disc. Cartilage destruction was measured by the percentage of radiolabel release. RESULTS: Fibroblasts, obtained from either rheumatoid arthritis (RA) or osteoarthritis synovial tissue, could mediate cartilage degradation if cocultured with the U937 macrophage cell line. Skin and RA bone marrow fibroblasts had no degradative effect on cartilage. Fibroblast-macrophage contact was not required for cartilage degradation. Cartilage degradation by synovial fibroblasts was inhibited by antibodies to tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6. Cartilage degradation was almost completely abrogated by a combination of antibodies to TNF alpha and IL-1 beta. Contact between fibroblasts and cartilage was shown to be essential. Antibodies to CD44, but not to intercellular adhesion molecule 1, markedly inhibited cartilage degradation. CONCLUSION: TNF alpha, IL-1 beta, and IL-6 were involved in the activation of synovial fibroblasts to cause cartilage degradation. Cartilage degradation occurred only when fibroblasts were in contact with cartilage. CD44 was demonstrated to be involved in the fibroblast-cartilage interaction.

Antibodies↗
PubMed1997

A one-week quadruple eradication regimen for Helicobacter pylori in routine clinical practice.

BACKGROUND: The addition of omeprazole to 1 week of standard triple therapy (tripotassium dicitrato bismuthate, tetracycline and metronidazole) has given a 98% eradication rate in 54 patients at 4-6 weeks in a research setting. We report the result of a similar 1-week regimen in 52 patients in routine clinical practice assessed at a mean of 8 months. METHODS: Fifty-two patients with peptic ulcer disease and antral biopsies containing Helicobacter pylori sensitive to metronidazole were given a 7-day course of treatment: omeprazole 20 mg b.d., tetracycline 500 mg q.d.s. and tripotassium dictitrato bismuthate chelate tablets 120 mg q.d.s., with metronidazole 400 mg five times daily for the last 3 days only. Completeness of eradication was assessed by a 13C-urea breath test at 4-26 months (mean 8 months). RESULTS: Forty-eight patients (92%) had a negative breath test. Three patients vomited on the last day of the course, otherwise the treatment was well tolerated with the expected minor side-effects of tongue discoloration, nausea and unpleasant taste. CONCLUSIONS: The efficacy of a modified 1-week standard triple therapy with omeprazole is confirmed and shown to be almost as effective in routine clinical practice as a similar regimen in a research setting.

Adult↗
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

Analysis of V kappa genes in rheumatoid arthritis (RA) synovial B lymphocytes provides evidence for both polyclonal activation and antigen-driven selection.

To define mechanisms of sustained activation of synovial B lymphocytes in RA, we studied hybridomas established from the local synovial B cell repertoire of two RA patients for V kappa gene expression and for antigen-binding specificity. The analyses revealed that members of the main V kappa families (I, II and III) were utilized at frequencies consistent with random V kappa gene family use. Furthermore, although the hybridomas expressed genes frequently seen in response to other self- and exogenous antigens, only one V kappa I- and two of three V kappa III-expressing hybridomas exhibited reactivity with self-antigens. Nucleotide sequence analysis revealed that all hybridomas, with the exception of rheumatoid factor (RF)-producing hybridomas, expressed V kappa genes highly related to known germ-line genes (99.3-100% homology) and that diversity was generated by deletions and random nucleotide insertions at the V kappa-J kappa junction. Examination of the few nucleotide changes seen with the V kappa genes revealed a predominance of silent to replacement changes. Moreover, most of these changes can be attributable either to allotypic variations or to limited random nucleotide replacements independent of antigen selection. In contrast, one IgG-RF (B4D8) exhibited predominantly replacement nucleotide changes in the complementarity-determining regions, suggestive of antigen-driven selection. The random expression of immunoglobulin variable region genes with no, or little, evidence of mutation in the synovial B lymphocyte repertoire, including natural polyreactive antibodies, alongside mutated IgG-RF, suggest that both polyclonal activation and antigen-driven responses occur in RA synovia.

Amino Acid Sequence↗
PubMed1995

Gastroenterology in the Trent Region in 1992 and a review of changes since 1975.

A survey of all gastroenterologists in the Trent Region (population 4.7 million) showed that in 1992 the number of upper gastrointestinal endoscopies had continued to rise considerably. There were 8.6 per thousand of the population. Colonoscopies had also increased to 1.4 per thousand. There had been a large fall in barium meal examinations to 4.8 per thousand. Barium enema examinations had increased slightly to 5.3 per thousand. The number of endoscopic retrograde cholangiopancreatographies (ERCPs) and variceal sclerotherapies had also increased by 54% and 21% respectively since 1986 and were available in most of the 20 hospitals. Percutaneous endoscopic gastrostomy had been introduced at most hospitals. Emergency endoscopy was readily available at night in only half the hospitals. Fourteen hospitals offered formal open access endoscopy. Intravenous sedation was used routinely in 12 hospitals. The rate for perforation at routine upper gastrointestinal endoscopy was 1 in 4500 and for death was 1 in 20,000. There were serious deficiencies in provision of facilities or staff, or both at 14 hospitals. The total number of gastroenterologists had only increased from 25 to 26 since 1986. Thus endoscopy workload continues to increase and diversify often without adequate staffing, facilities, and funding.

Barium Sulfate↗