Search PubMed⌕ Search

Biomedical subjects

J M Neuberger

Publications and source records attributed to J M Neuberger.

At least 91 records · Page 5Linked to original sources
PubMed1989

Intercellular adhesion molecule 1 on liver allografts during rejection.

The expression of intercellular adhesion molecule 1 (ICAM-1), a ligand for the leucocyte adhesion receptor lymphocyte-function-associated antigen 1 (LFA-1), was studied on liver tissue after transplantation. There was greater ICAM-1 expression on bile ducts, endothelium, and perivenular hepatocytes (structures affected by the rejection process) in patients with acute rejection than in donor livers, patients with stable transplants, or patients with non-rejection complications. The expression on bile ducts and hepatocytes was greater in patients in whom there was progression to chronic, irreversible rejection. In patients with resolving rejection ICAM-1 expression was greatly reduced after high-dose corticosteroid treatment. The expression in patients with non-rejection complications and in those with long-term stable grafts was similar to that seen in the donor controls. The induction of ICAM-1 on tissues may be an important step in the development of the inflammatory response of rejection and in determining which cells are the targets of immune damage. The reduction of ICAM-1 expression seen after successful treatment with high-dose corticosteroids suggests that this might be an important mode of action of these drugs.

Acute Disease↗
PubMed1989

Soluble interleukin-2 receptors in serum and bile of liver transplant recipients.

Soluble interleukin-2 receptors (IL2R) were measured as markers of lymphocyte activation in serum and bile of liver transplant recipients. Serum and biliary levels were significantly higher in patients with acute rejection than in those with other complications (serum p less than 0.0025, bile p less than 0.001) or stable grafts (both p less than 0.0001). Levels rose 24 h before rejection could be detected by conventional liver tests. Biliary levels were more specific and sensitive than serum levels for rejection. Local production of IL2R accounted for the high levels in bile; the bile to serum ratio of IL2R was greater than that of albumin in 16 of 18 patients with acute rejection. Serum levels were high early in the course of chronic rejection but fell as it progressed to end-stage. Measurement of soluble IL2R may have a role in the early diagnosis of acute rejection and in identifying patients with chronic rejection in whom further immunosuppression will provide no benefit.

Acute Disease↗
PubMed1989

Immuno-isolation and culture of biliary epithelial cells from normal human liver.

Biliary epithelial cells (BEC) lining the intra-hepatic biliary ducts are the site of damage in several immunologically mediated liver diseases. BEC are difficult to isolate since they represent only 5% of the total cell number in normal liver. In this communication, a novel method for their isolation from normal liver is presented using a monoclonal antibody (HEA125) with specificity for an epithelial cell surface glyco-protein reported to be expressed in liver only by biliary epithelium. By combining differential density centrifugation and immuno-magnetic separation using HEA125 pure BEC (10(5) cells/g fresh tissue) were prepared routinely. These cells were maintained in culture for up to 4 weeks with significant increases in cell numbers. The ability to prepare BEC from human liver offers an opportunity to develop In Vitro models to investigate the aetiology of diseases of intra-hepatic biliary epithelium.

Antibodies, Monoclonal↗
PubMed1989

Liver transplantation.

The 1-year survival rates of around 70% that are now being achieved have resulted in the acceptance of liver transplantation as a treatment for end-stage liver disease. The number of patients undergoing transplantation is increasing rapidly and the indications are widening. More patients are being transplanted for acute liver failure following the recent encouraging reports of successful grafting in this condition. The proportion of patients transplanted for liver cancer is falling as it becomes apparent that 80% of patients will die from recurrent disease. The selection of candidates and timing of transplantation continue to pose difficult clinical problems. Although the surgical and anaesthetic aspects of liver transplantation have been greatly improved, the 30-day mortality remains high at around 30% and postoperative complications, especially infection and rejection, continue to be major problems. However, rehabilitation is excellent for most patients and liver transplantation should no longer be considered an experimental procedure.

Humans↗
PubMed1989

Hepatic endothelial cells. Targets in liver allograft rejection?

Hepatic endothelial cell damage was evaluated in patients following liver transplantation using 2 serum markers: hyaluronic acid (HA), which measures hepatic endothelial cell function, and factor VIII related antigen (VIIIRAg), an indicator of generalized endothelial damage. HA was elevated in rejection (median 22.3 x control) when compared with stable patients (3.7 x control; P less than 0.00001) and those with posttransplant complications not related to rejection (6.8 x control; P less than 0.0005). The highest levels were seen in patients with chronic rejection (28.7 x control). Levels were also elevated in acute rejection (21.3 x control), and the highest levels in this group were seen in patients who subsequently developed chronic rejection (25.2 x control). Serial studies demonstrated that HA increased 24 hr before serum bilirubin in patients developing acute rejection. VIIIRAg was elevated in all posttransplant patients with no significant difference between rejection and other complications. These results show that hepatic endothelial dysfunction occurs during acute and particularly chronic rejection of liver allografts suggesting that VECs may be an important target of the immune response. Measurement of HA may allow for the early diagnosis of acute rejection and the identification of patients at risk of developing chronic rejection.

Adolescent↗
PubMed1987

Halothane hepatitis: attempt to develop an animal model.

Patients with liver damage following halothane anaesthesia (halothane hepatitis) have circulating antibodies reacting with plasma membrane determinants present on hepatocytes isolated from rabbits previously exposed to halothane. In an attempt to develop an animal model of halothane hepatitis, rabbits were immunised with hepatocytes isolated from litter mates previously exposed to halothane; this resulted in the generation of antibodies to both normal and halothane related liver cell determinants detected by both immunofluorescence and indirect cytotoxicity. Exposure of these immunised rabbits to halothane resulted in the disappearance of the halothane-related antibody, presumably due to its reaction with the liver-cell membrane halothane-related antigen; this, however, could not be proved since immunisation with halothane hepatocytes induced the presence of antibodies on the recipient hepatocytes. Although both human and rabbit lymphocytes were directly cytotoxic in vitro to these antibody coated hepatocytes, no evidence of liver damage could be detected. Thus, if immune mechanisms are involved in the pathogenesis of halothane hepatitis, other factors, probably related to idiosyncratic host immune responses, must be implicated.

Animals↗
PubMed1987

A major histocompatibility complex class III allotype (C4B 2) associated with primary biliary cirrhosis (PBC).

Primary Biliary Cirrhosis (PBC) is a female associated disease of unknown aetiology, although there is evidence of immunological abnormalities. There is no known cure; liver damage is progressive and eventually fatal, although transplantation can prevent patient death. Data presented here show, for the first time, a strong association in Caucasoids between PBC and the major histocompatibility complex (MHC). 45% of patients studied, compared with only 17% in a control group, expressed an MHC Class III allotype C4B 2 (pc = 0.014). Polymorphisms of MHC Class I, Class II, and other Class III gene products which flank the C4 genes were not found to be associated with the disease. Although we cannot rule out the involvement of other loci linked to the C4B 2 complement gene, the data provide strong evidence that this genetic area is implicated in the pathogenesis of this disease.

Complement C3↗
PubMed1986

Primary biliary cirrhosis in men.

To determine whether primary biliary cirrhosis differed in men and women we reviewed the presenting features and clinical course of 39 men and 191 women with primary biliary cirrhosis followed at this unit between 1970 and 1984. Age and severity of disease at time of diagnosis were similar in both groups. Pruritus was significantly less common in men than in women both at diagnosis and throughout the period of follow up (p less than 0.01). The difference in incidence of pruritus at diagnosis was most evident when the male group were compared with a group of premenopausal women, an observation which is consistent with involvement of sex steroid metabolism in the origin of pruritus. Skin pigmentation was also less marked in men at diagnosis (p less than 0.05). Autoimmune associated conditions, especially sicca syndrome, were more common in women. Survival was similar among men and women although hepatoma developed significantly more frequently in male patients (p less than 0.01).

Female↗
PubMed1984

Diversity of autoantibodies in primary biliary cirrhosis and chronic active hepatitis.

The presence of autoantibodies in the serum of 110 patients with primary biliary cirrhosis (PBC), 50 with HBsAg negative chronic active hepatitis (HBsAg- CAH) and 30 with HBsAg positive chronic active hepatitis (HBsAg+ CAH) was assessed using two methods: indirect immunofluorescence on cells grown in tissue culture (HEp-2 cell line) or standard mouse tissue sections, and counter immunoelectrophoresis (CIE) with soluble tissue extracts. Anti-nuclear antibodies (ANA) were found in 38% of sera from patients with PBC using HEp-2 cells compared with 10% using mouse tissue. A variety of staining patterns were detected including a pattern of multiple nuclear dots. In contrast, ANA was detected in 70% of sera from patients with HBsAg- CAH and 27% with HBsAg+ CAH. Using CIE four distinct antibody antigen systems were detected: Ro (SS-A), La (SS-B) and two new systems, designated XH and XR, reacting with extracts of human spleen and rabbit thymus, respectively. Correlation of the presence of antibody with clinical conditions confirmed the close association between anti-centromere antibody and sclerodactyly in patients with PBC and indicated an association between 'multiple nuclear dot' staining and the sicca syndrome in PBC. No association was found between the presence of either Ro or La antibody and the sicca syndrome in patients with PBC.

Antibodies, Antinuclear↗
PubMed1982

Anticentromere antibody in primary biliary cirrhosis.

An autoantibody specific for the centromere region of chromosomes and recently detected in the serum of patients with scleroderma was found in ther serum of 10 (9.1%) of 110 consecutive patients presenting with primary biliary cirrhosis. It was found exclusively among those with scleroderma, giving a prevalence of 50% in that group, and all patients with telangiectasia or calcinosis had the antibody. It was not found in 80 patients with chronic active hepatitis, including the 'autoimmune' variety. The pathogenetic significance of anticentromere antibody is not yet established, but this study confirms its specificity for scleroderma in the context of primary biliary cirrhosis.

Antibody Specificity↗