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Biomedical subjects

B F Warren

Publications and source records attributed to B F Warren.

At least 73 records · Page 4Linked to original sources
PubMed1997

Brush cytology in the diagnosis of neoplasia in Barrett's esophagus.

Esophageal cytology may improve sensitivity for the detection of malignancy but can be difficult to interpret in the presence of inflammation. To assess the value of cytology in assessing patients with Barrett's esophagus a retrospective review was performed. One hundred and sixty two patients (87 esophageal/gastroesophageal junction adenocarcinoma, 65 non-dysplastic Barrett's esophagus and 10 dysplastic Barrett's esophagus) had biopsies and brushings taken for histological and cytological assessment. Eighty two of 92 patients with carcinoma or high-grade dysplasia had true positive malignant cytology. Seven of 65 patients with non-dysplastic but inflamed Barrett's esophagus had false positive malignant cytology. One of these patients had an esophagectomy on the basis of cytology but no tumor was found in the resection specimen. This translates into an 89% sensitivity and specificity of cytology for the detection of esophageal columnar neoplasia. Cytology from Barrett's esophagus can be misleading in the presence of severe inflammation. Cells from a benign Barrett's ulcer may appear frankly malignant when examined in isolation. Esophagectomy should not be performed on the basis of cytological evidence alone.

Adenocarcinoma↗
PubMed1997

Treatment of ulcerative colitis in the cottontop tamarin using antibody to tumour necrosis factor alpha.

BACKGROUND: The aetiology and pathophysiology of ulcerative colitis remains unclear; however, there is increasing recognition of the critical role of inflammatory cytokines in the pathogenesis of this disease. Among these, tumour necrosis factor alpha (TNF alpha) seems to play an important role. AIM: To study the effects of an engineered human monoclonal antibody to TNF alpha (CDP571) in the treatment of idiopathic ulcerative colitis in the cottontop tamarin. METHODS: Six cottontop tamarins with confirmed ulcerative colitis received repeated doses of CDP571. Progression of disease was assessed by measuring both body weight and rectal biopsy pathology. RESULTS: All animals showed a rapid improvement in clinical condition and rectal biopsy pathology that was maintained following completion of the therapy. CONCLUSION: These studies indicate the efficacy of selective antibody therapy to TNF alpha for the treatment of ulcerative colitis in a primate and suggest that similar therapy in human could be of value.

Animals↗
PubMed1996

Mucus glycoproteins and their role in colorectal disease.

In this review, the nature and impact of progress in the study of mucins is outlined, emphasizing the current understanding of the structure and physiological function of these molecules in the colorectum. The use of new methods for preparation and separation has led to improvements in the analysis of mucins; these are detailed, as are their difficulties and pitfalls. Results obtained with these methods are correlated with long-established histochemical techniques and the use of chemical, lectin, and antibody reagents for general and specific detection of mucins in all procedures is described. Improvements in the detection and analysis of mucins in biopsy-size tissue samples and in larger numbers of individual clinical cases have now permitted a much wider approach to the pathological evaluation of mucin biology and progress with these techniques is outlined. The significance of the discovery of a family of mucin genes is presented and new concepts of mucin structure resulting from these studies are described. Bacterial degradation of the mucus layer at the surface of the colorectal mucosa is considered in line with the homeostatic relationship with mucosal mucin synthesis. Finally, the implications of abnormal mucins in colorectal disease are considered in the light of recent methodological advances.

Colorectal Neoplasms↗
PubMed1996

Heterogeneous expression of carcinoembryonic antigen in the normal colon and upregulation in active ulcerative colitis.

Using a technique of tolerization, a murine monoclonal antibody (MAb 2E8) has been raised which displays regional differences in reactivity in the epithelium of the normal human colon and increased reactivity in active ulcerative colitis. MAb 2E8 (IgG1) was highly colon-specific and gave higher immunoperoxidase staining scores in the proximal colonic mucosa compared with paired rectal sections (P < 0.02). Expression of the antigen reactive with MAb 2E8 was enhanced in active ulcerative colitis compared with quiescent ulcerative colitis (P < 0.05) and normal controls (P < 0.001). Western blotting and indirect immunofluorescent screening on transfected cell lines established that MAb 2E8 was reactive with carcinoembryonic antigen (CEA). This is the first demonstration of regional differences in the expression of CEA in the normal colon and indicates upregulation of this molecule in active ulcerative colitis.

Adult↗
PubMed1996

Cytomegalovirus infection and colonic perforation in renal transplant patients.

Cytomegalovirus (CMV) infection in immunocompromised patients is a major cause of morbidity and mortality. A well-documented manifestation of gastrointestinal CMV infection is gastrointestinal haemorrhage. In contrast, CMV-associated intestinal perforation has rarely been reported after transplantation, although it is well documented in AIDS patients. Three patients are reported who received their first cadaveric renal transplant in 1994 and subsequently developed CMV disease. During the course of their CMV illness, which was treated with ganciclovir, each presented with clinical suspicion of peritonitis and proceeded to laparotomy. All three were found to have sigmoid colon perforations with histological evidence of CMV infection. Following bowel resection and defunctioning, two patients made an uneventful recovery and have had the continuity of their bowel restored, but one died of overwhelming sepsis within hours of surgery. The explanation for the apparent clustering of this rare condition in transplant patients is uncertain.

Aged↗
PubMed1996

Colonic mucins in ulcerative colitis: evidence for loss of sulfation.

Colonic tissue obtained at surgery from control individuals and patients with ulcerative colitis was used to isolate mucins and to prepare mucin glycopolypeptides by pronase digestion. These were compared with mucins labelled with [35S] sulfate and [3H]-glucosamine after organ culture tissue samples from the same patients. A significant loss of mucin sulfation was detected in the colitis patients by both metabolic labelling and chemical analysis of the glycopolypeptides. A change in the size distribution of purified mucin oligosaccharides fractionated on BioGel P6 after release by beta-elimination was seen in both radiolabelled and non-labelled colitis mucins compared with controls. Amino acid analysis of the glycopolypeptides showed a close similarity to the expected ratio of serine:threonine:proline for MUC2 and did not vary between control and colitis groups. Analysis of the mucins confirmed > 90% purity in the labelling experiments, characteristic behaviour on density gradient centrifugation and agarose gel electrophoresis in control and ulcerative colitis groups and differences in sulfation and turnover at various sites in the normal colon.

Amino Acids↗
PubMed1996

Cytokines in the cotton top tamarin model of human ulcerative colitis.

The cotton top tamarin is a unique model of human ulcerative colitis. This disease is clinically and histologically similar. It is also complicated in some cases by colon cancer. The cotton top tamarin provides an appropriate animal model for assessing new treatments in inflammatory bowel disease.

Animals↗
PubMed1996

Detection of exfoliated carcinoma cells in colonic luminal washings by identification of deranged patterns of expression of the CD44 gene.

AIMS: To investigate whether colonic cancer cells exfoliated into the lumen of the organ can be detected by identification of their abnormal CD44 gene products. METHODS: Exfoliated cells were obtained by centrifugation of saline wash-outs of 27 surgically resected colon specimens obtained from 15 patients with carcinoma, seven with ulcerative colitis and five with Crohn's disease. After extracting cellular mRNA, amplification by the reverse transcription-polymerase chain reaction (RT-PCR) technique and analysis by Southern blot hybridisation was carried out to examine the levels and patterns of transcription of exons 11(v6), and 12(v7) and intron 9 of the CD44 gene. The transcription of these CD44 components was also examined by RT-PCR of snap-frozen solid tissue specimens from 11 of the above patients with colorectal carcinoma, seven with ulcerative colitis and five with Crohn's disease. RESULTS: Abnormal expression of exons 11(v6) and 12(v7) was detected in exfoliated cells from 11 (73%) of 15 patients with carcinoma, but not in any patients with inflammatory bowel disease (IBD). The retention of intron 9 in CD44 mRNA transcripts was detected in washings from four (27%) carcinoma specimens but not in washings from non-malignant specimens. It was confirmed that in solid tissue samples from the same carcinomas there was abnormal over-expression of numerous alternatively spliced CD44 species containing transcripts of exons 11 and 12 and retention of intron 9. Low level expression of these exons was detected in tissue from inflammatory lesions from five of seven patients with ulcerative colitis and four of five with Crohn's disease. The retention of intron 9 was not seen in normal mucosa nor IBD. CONCLUSION: Abnormal expression of the variant exons and of intron 9 of the CD44 gene in tumour cells exfoliated into the colonic lumen may be helpful markers for the early, non-invasive, diagnosis of colorectal cancer.

Aged↗
PubMed1995

Abnormal retention of intron 9 in CD44 gene transcripts in human gastrointestinal tumors.

We have recently identified a new exon of the CD44 gene and demonstrated abnormal retention of a noncoding section, intron 9, in mRNA from bladder carcinomas. To analyze this further, the present study examined CD44 gene expression in cell lines from 14 esophageal, 3 colonic, and 4 breast carcinomas and in fresh samples from 20 colorectal carcinomas and corresponding normal colonic mucosa, using reverse transcriptase followed by the polymerase chain reaction (RT-PCR). This confirmed that there was abnormal assembly of several exons of the gene in cell lines and in tumor tissues from these organs. However, the most striking new finding was that intron 9 was present in RNA from 11 esophageal, 3 colon, and 1 breast carcinoma cell line, respectively. This was confirmed by RNase and DNase digestion analysis. Moreover, it was detected both in nuclear and cytoplasmic mRNA fractions, indicating that abnormal splicing of pre-mRNA occurs in cancer cells. The abnormal retention of intron 9 in CD44 gene transcripts was also demonstrated in tumor tissues from 16 (80%) of 20 patients with colon carcinoma, but there was no correlation with Dukes' stage. The biological significance of these observations is not yet understood. However, it is clear that, as with the abnormal expression pattern of CD44 variant exons, intron 9 retention is a good-candidate molecular diagnostic tool for colorectal carcinomas.

Base Sequence↗
PubMed1995

Synchronous proctocolectomy and ileoanal pouch formation and the risk of Crohn's disease.

There is controversy on the advisability of one-stage proctocolectomy and the formation of an ileoanal pouch. Accurate preoperative diagnosis is essential to avoid the error of constructing a pouch in a patient with Crohn's disease. Twenty-four consecutive patients undergoing subtotal colectomy for inflammatory bowel disease were reviewed. All patients had been treated with systemic steroids, 23 were on 5-aminosalicylates and 11 on azathioprine. The preoperative diagnoses, based on a combination of clinical features, colonoscopy, barium enema and biopsy histology, were ulcerative colitis (19), Crohn's disease (four) and inflammatory bowel disease (unclassified) (one). The final diagnosis was made on histological examination of the resected specimen. A discrepancy between initial and final diagnosis occurred in eight patients. In three, the diagnosis was changed from ulcerative colitis to Crohn's disease. Three preoperative diagnoses of Crohn's disease were changed to ulcerative colitis (one), Behçet's disease (one) and diverticulitis (one) on final histology. These data suggest that caution should be exercised in performing synchronous proctocolectomy with the formation of an ileoanal pouch.

Adult↗
PubMed1995

South Asian and European colitics show characteristic differences in colonic mucus glycoprotein type and turnover.

South Asians in Britain have a high incidence of ulcerative colitis and a low incidence of colorectal cancer. The pattern of mucus production in 12 South Asian and 16 European colitics and a control group of 19 South Asians was studied. Three types of mucin were identified after organ culture of colonic biopsy specimens with a dual label of [3H]-glucosamine and sodium [35S]-sulphate: type A had a high [35S]:[3H] ratio and high incorporation ([3H] dpm/micrograms DNA > 500); type B had a low ratio and high incorporation; and type C had low incorporation but with either high (C1) or low (C2) ratios. European colitic mucins show a significant reduction in the level of sulphation detected by mucin histochemistry with high iron diamine/Alcian blue staining, together with predominantly type B or C2 mucins (low sulphation). South Asian colitics showed histochemically normal patterns of high sulphation and largely type A and C1 mucins (high sulphation). There was no correlation of mucin type with disease activity index in either ethnic group. The appearance of apparently normal mucin in patients with ulcerative colitis may be a useful marker for the identification of a subgroup at low risk of colorectal cancer.

Asia, Southeastern↗
PubMed1995

An unusual case of colonic angiodysplasia.

An unusual case of a colonic vascular anomaly resembling angiodysplasia associated with right sided diverticular disease is presented. The patient, a 74 year old man, presented with a four day history of rectal bleeding and subsequently underwent hemicolectomy. The resected specimen was flushed out with heparin-saline solution and injected with a barium-gelatine mixture. Preoperative barium enema revealed right sided diverticula, whereas post-resection angioradiography revealed the "coral reef" vascular anomaly consistent with angiodysplasia. Histology confirmed the presence of both diverticular disease and angiodysplasia. This case report highlights the importance of considering a vascular anomaly in patients presenting with rectal bleeding despite the presence of another radiologically demonstrable anatomical lesion.

Aged↗
PubMed1995

Detection of herpesvirus DNA in cottontop tamarins: no association with colitis.

Colitis occurs spontaneously in the cottontop tamarin; it shares similar clinical, endoscopic and histological features with, and has a similar response to treatment as, human ulcerative colitis. An association between human ulcerative colitis and the presence of DNA from multiple herpesviruses (human herpesvirus 6 (HHV-6), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in the colon has been described. Intestinal herpesvirus infection may be involved in the pathogenesis of this condition. In a pilot study, coded full thickness colonic specimens from 27 cottontop tamarins were examined for the presence of HHV-6, CMV and EBV DNA using the nested polymerase chain reaction. The sections represented a spectrum of disease activity ranging from histologically normal bowel to severe colitis. A low prevalence of DNA from these viruses was found, which bore no relation to the presence of inflammation. Although these herpesviruses may have a pathogenetic role in human ulcerative colitis, they are not associated with colitis in this animal model.

Animals↗
PubMed1994

Two different glycosyltransferase defects that result in GalNAc alpha-O-peptide (Tn) expression.

This study shows for the first time that different glycosyltransferase defects in the biosynthesis of O-linked oligosaccharides give rise to the same GalNAc alpha-O-Ser/Thr determinant on Tn erythrocytes and colorectal carcinoma cells. The O-linked oligosaccharides isolated from the glycophorins of Tn erythrocytes contained predominantly alpha-N-acetylgalactosamine-O-Ser/Thr (Tn antigen) and sialyl-Tn. A marked reduction in normal sialylated oligosaccharides was also observed. Monoclonal antibody BRIC 111 raised against Tn erythrocytes reacted with both Tn erythrocytes and colorectal carcinoma tissues. Weak staining was detected in the supranuclear area and at the surface membranes in normal colorectal cells, but was absent from goblet cell vesicles. An increase in supranuclear staining over controls was found in tumour tissue and in the majority of resection margin specimens. The highest levels of staining were present in transitional mucosa, adjacent to the tumours where goblet vesicles were also positive. Glycosylation defects in the same patients were further studied by determination of the activity of glycosyltransferases in mucosal tissue from control and cancer patients. The reduction in or loss of beta 1-3 N-acetylglucosaminyl transferase activity to GalNAc-peptide in asialo-ovine submaxillary gland glycoprotein was detected by direct assay and by isolation of the oligosaccharides from the incubation products. No differences in N-acetylglucosaminyl-, galactosyl- or sialyl-transfer to Gal beta 1-3GalNAc in antifreeze glycoprotein or in sialyl transferase to asialo-ovine submaxillary gland glycoprotein were detected. Our study shows that the GalNAc alpha-O-Ser/Thr determinant on Tn erythrocytes and in colorectal carcinoma results from different glycosyltransferase defects in separate biosynthetic pathways for haematopoietic and epithelial tissues.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Polypoid mucosal prolapse in a pelvic ileal reservoir.

A case of a patient who developed a polypoid area of mucosal prolapse three and a half years after having an ileoanal pouch for ulcerative colitis is presented. This seems to be the first published report. This new manifestation of mucosal prolapse in a pelvic ileal reservoir underlines that the pouch as a neorectum is subject to disorders familiar in the rectum.

Adult↗