ABSTRACT
Immune mechanisms, possibly involving cell-surface molecules such as CD44, have been invoked to explain the pathogenesis of inflammatory bowel disease. We used monoclonal antibodies against epitopes encoded within the variable region of CD44 to investigate CD44 isoform expression in colon, small intestine, and liver in patients with various intestinal disorders and in controls. Biopsy samples from patients with ulcerative colitis showed significantly increased epithelial expression of CD44 isoforms containing the v6 and v3 epitopes, detected with antibodies 2F10 and 3G5, respectively. CD44v6 was detected on colonic crypt epithelial cells in 23 of 25 ulcerative colitis samples compared with 3 of 18 colonic Crohn's disease samples (p = 3.0 x 10(-6); odds ratio 57.5 [95% CI 6.83-702]) and 3 of 52 controls (22 normal colon, 10 infective colitis, 2 radiation colitis, and 18 colonic Crohn's disease; p < 1 x 10(-8); odds ratio 199 [25.5-2294]). No significant expression of CD44v6, CD44v3, or CD44v8/9 was found in samples of normal proximal colon from 4 patients with distal ulcerative colitis, whereas samples from the affected area showed staining for CD44v6 and CD44v3. No expression of CD44 variants was found in 15 samples of normal small intestine, 11 small-bowel pouchitis, 8 coeliac disease, 3 small-bowel Crohn's disease, 6 normal liver, 6 primary biliary cirrhosis, or 9 primary sclerosing cholangitis. The high intensity of CD44v6 and v3 epitope expression on crypt epithelial cells in ulcerative colitis suggests that CD44 isoforms may have an important role in ulcerative colitis. Their detection could have diagnostic potential in differentiating ulcerative colitis from other forms of colonic inflammation including Crohn's disease.
Subject(s)
Carrier Proteins/analysis , Colitis, Ulcerative/immunology , Crohn Disease/immunology , Receptors, Cell Surface/analysis , Receptors, Lymphocyte Homing/analysis , Antibodies, Monoclonal , Carrier Proteins/chemistry , Carrier Proteins/genetics , Epitopes/analysis , Female , Gastrointestinal Diseases/immunology , Humans , Hyaluronan Receptors , Male , Middle Aged , Receptors, Cell Surface/chemistry , Receptors, Cell Surface/genetics , Receptors, Lymphocyte Homing/chemistry , Receptors, Lymphocyte Homing/geneticsABSTRACT
Nine patients are described with jaundice, upper abdominal pain and malaise attributable to dextropropoxyphene hepatotoxicity. In each case the history was suggestive of large bile duct obstruction. All patients underwent ultrasound examination and percutaneous liver biopsy. Three patients also underwent endoscopic retrograde cholangio pancreatography. The histological features of the biopsies concur with previously reported cases of dextropropoxyphene hepatotoxicity. The histological changes seen on biopsy were remarkably constant, consisting of centrilobular cholestasis, portal tract inflammation and bile duct abnormalities, in all cases mimicking large bile duct obstruction. Fifteen previous patients with probable dextropropoxyphene hepatotoxicity have been described. The occurrence of 9 further cases at one centre, 6 presenting within 12 months, suggests that it is much more common than previously assumed and may be misdiagnosed as large bile duct obstruction.
Subject(s)
Chemical and Drug Induced Liver Injury , Dextropropoxyphene/adverse effects , Adult , Aged , Female , Humans , Liver Diseases/pathology , Male , Middle AgedABSTRACT
Ovarian hyperstimulation syndrome (OHSS) is a potentially fatal condition associated with the therapeutic induction of ovulation in infertility. Liver function abnormality has been previously reported in four patients, one of whom had ultrastructural abnormalities on liver biopsy. This paper describes a patient presenting with severe OHSS 16 days after ovulation had been induced. Liver function abnormality was apparent 11 days later, with a sustained rise in alkaline phosphatase and aspartate aminotransferase (AST) which lasted up to 2 months. A liver biopsy performed during the second month of her protracted hospital admission showed marked zonal fatty change (acinar zone 1) and associated inflammation, with mitochondrial crystalline inclusions and rough endoplasmic reticulum dilatation on electron microscopy. This report discusses the clinical features and possible aetiological factors.
Subject(s)
Liver Diseases/etiology , Ovulation Induction/adverse effects , Adult , Alkaline Phosphatase/biosynthesis , Aspartate Aminotransferases/biosynthesis , Bilirubin/analysis , Biopsy , Chorionic Gonadotropin/therapeutic use , Female , Humans , Liver Diseases/metabolism , Liver Function Tests , Menotropins/therapeutic use , Serum Albumin/analysis , gamma-Glutamyltransferase/analysisABSTRACT
Diclofenac is a widely used non-steroidal anti-inflammatory drug, being the most commonly prescribed of its kind in the world. This paper describes five cases of hepatitis with clinical features indicating a direct link with diclofenac. All the patients presented with an acute hepatitis, three being jaundiced. They gave a history of taking diclofenac up to the time of presentation, four of the five having started the drug within the previous 3 months. There were no other features in the histories to suggest alternative causes for the liver dysfunction. Liver function tests were grossly abnormal in all cases, showing a hepatitic picture. A liver biopsy was performed in 4 cases, and showed features of an acute hepatitis with inflammation and hepatocyte damage dominating. The liver dysfunction returned to normal on drug withdrawal in four of the five cases, with full recovery by 3 months. One patient developed steroid-responsive chronic active hepatitis. Hepatotoxicity associated with diclofenac is documented, but previously only a few isolated cases have been described. The occurrence of five cases in one gastroenterology unit over a 12-month period suggests that hepatitis associated with diclofenac may be commoner than previously supposed.
Subject(s)
Chemical and Drug Induced Liver Injury/pathology , Diclofenac/adverse effects , Aged , Biopsy , Chemical and Drug Induced Liver Injury/complications , Chemical and Drug Induced Liver Injury/physiopathology , Female , Humans , Jaundice/etiology , Liver/pathology , Liver Function Tests , Middle AgedABSTRACT
Thirty patients who had not previously received treatment with factor VIII concentrate or who had been treated only infrequently with factor VIII concentrate were studied after a transfusion of factor VIII. Tests of liver function were performed frequently. Four patients had evidence of chronic liver disease before transfusion. In 17 of the remaining 26 patients serum transaminase activities became raised and 10 patients developed jaundice. All of the nine patients who had not previously received factor VIII transfusion developed non-A non-B hepatitis. Four out of 10 patients followed up for a year had persisting abnormalities of liver function. The pattern of illness suggests that more than one serotype of non-A non-B hepatitis virus may be transmitted by factor VIII concentrate prepared by the National Health Service from volunteer donors in the United Kingdom.
Subject(s)
Factor VIII/adverse effects , Hemophilia A/therapy , Hepatitis C/etiology , Hepatitis, Viral, Human/etiology , Adolescent , Adult , Aged , Antibodies, Viral/analysis , Child , Factor VIII/therapeutic use , Female , Hepatitis C/blood , Hepatitis C/transmission , Hepatitis, Viral, Human/immunology , Humans , Male , Middle Aged , Prospective Studies , Time Factors , Transaminases/bloodABSTRACT
Mallory bodies (MBs) were prepared in 95% pure form from a case of human chronic alcoholic liver disease. A protein referred to as Mallory body protein (MBP), was isolated from MB by reduction and alkylation which gave one band an SDS-polyacrylamide electrophoresis. Antisera were raised to both purified MBs and MBP in rabbits and a goat. Both antisera, after absorption with spleen cells, specifically reacted immunohistochemically with MBs in frozen sections from patients with alcoholic liver disease. They also reacted with small granular structures in hepatocytes which are interpreted as a precursor or degradation product of MBs. The anti-MB serum also stained MBs in trypsinised paraffin sections in the immunoperoxidase procedure. Neither antisera reacted with normal liver or skin, and the reactivity of anti-MB and MBP sera for MBs was not abolished by absorption with prekeratin; these results indicate that MBs contain unique antigenic determinants not present in prekeratin. It is concluded that MBs are not simply composed of intermediate filament proteins.