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D H Adams

Publications and source records attributed to D H Adams.

At least 19 recordsLinked to original sources
PubMed1992

Detection of circulating intercellular adhesion molecule-1 in chronic liver diseases.

The leucocyte adhesion molecule intercellular adhesion molecule-1 is induced on bile ducts in patients with primary biliary cirrhosis and primary sclerosing cholangitis and may be involved in targeting immune damage to these structures. It has recently been reported that, when activated, in vitro lymphocytes release a soluble form of intercellular adhesion molecule-1 that can also be detected in human serum. Because it is functionally active, this circulating intercellular adhesion molecule-1 might play a role in regulating inflammation by blocking adhesion. We used an enzyme-linked immunosorbent assay to detect circulating intercellular adhesion molecule-1 in the serum of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Levels of circulating intercellular adhesion molecule-1 were markedly elevated in primary biliary cirrhosis and primary sclerosing cholangitis when compared with other chronic liver diseases. Circulating intercellular adhesion molecule-1 is probably derived from activated lymphocytes rather than from bile ducts because biliary epithelial cells from patients with primary biliary cirrhosis did not release circulating intercellular adhesion molecule-1 when stimulated to express the membrane-bound molecule in vitro. These studies are the first to demonstrate circulating intercellular adhesion molecule-1 in chronic inflammatory diseases that are characterized by strong tissue expression of intercellular adhesion molecule-1 and as such suggest a potential immunoregulatory role for circulating adhesion molecules. The very high levels detected in primary biliary cirrhosis and primary sclerosing cholangitis probably reflect lymphocyte activation, which is further evidence of immune pathogeneses for these diseases.

Bilirubin↗
PubMed1992

Is the intercellular adhesion molecule-1/leukocyte function associated antigen 1 pathway of leukocyte adhesion involved in the tissue damage of alcoholic hepatitis?

Alcoholic hepatitis is characterised histologically by an intense inflammatory cell infiltrate made up predominantly of neutrophils but including other cell types, particularly lymphocytes. Leukocyte cytotoxicity requires cell adhesion, which is mediated via receptors on the leukocyte surface including leukocyte function associated antigen-1 (LFA-1) which binds to the ligand intercellular adhesion molecule-1 (ICAM-1) on the target cell. The distribution of ICAM-1 and LFA-1 expression in liver biopsy specimens from patients with alcoholic liver disease was examined to ascertain whether this pathway of leukocyte adhesion is involved in the tissue damage of alcoholic hepatitis. Specimens were stained for ICAM-1 and LFA-1 by a three step immunoalkaline-phosphatase method using monoclonal antibodies against ICAM-1 and LFA-1. LFA-1 staining on portal tract inflammatory cells and parenchymal inflammatory cells and ICAM-1 staining on liver components were examined. ICAM-1 expression on hepatocytes was significantly greater in alcoholic hepatitis compared with fatty liver (p less than 0.001) and normal controls (p less than 0.01). ICAM-1 expression correlated with the histological degree of hepatocellular damage (tau = 0.79; p = 0.0005) and parenchymal inflammation (tau = 0.65; p less than 0.001, and with LFA-1 expression on parenchymal leukocytes (tau = 0.63; p = 0.01). The ICAM-1/LFA-1 pathway may therefore be involved in leukocyte mediated tissue damage during alcoholic hepatitis.

Antibodies, Monoclonal↗
PubMed1992

Experimental graft arteriosclerosis. I. The Lewis-to-F-344 allograft model.

Progressive graft arteriosclerosis is responsible for the majority of late deaths occurring in cardiac transplant recipients. In order to define a model of this disease in the rat, we exchanged heterotopic cardiac allografts between MHC-compatible inbred strains. Lewis rats served as donors and F-344 rats as recipients. Twenty allografts were followed by daily palpation and removed at the time of terminal rejection or on the 120th postoperative day for pathologic study. Sixteen allografts (80%) survived at least three weeks, and five allografts (25%) survived indefinitely. The majority of arteries (greater than 90%) examined demonstrated significant intimal disease; histologic findings in lesions in allografts rejecting at early time points included intense mononuclear cell infiltration of the intima, while lesions in long-term-surviving allografts demonstrated fibrous intimal thickening, which is characteristic of graft arteriosclerosis seen clinically. A limited course of cyclosporine therapy in F-344 recipients increased the incidence of indefinite allograft survival from 25% to 86%, and was associated with a modest reduction in the amount of intimal disease observed. These results suggest that this model should be useful in future studies regarding the pathogenesis and therapy of cardiac graft arteriosclerosis.

Animals↗
PubMed1991

Transforming growth factor-beta induces human T lymphocyte migration in vitro.

In addition to its activities as a growth factor, recent studies suggest an immunoregulatory role for transforming growth factor-beta (TGF-beta). In this context we have demonstrated that TGF-beta is a potent chemotactic factor in vitro for human T lymphocytes at a concentration of 40 fM and for monocytes at a concentration of 0.4 fM but that it has no chemotactic activity for neutrophils. Furthermore, using an assay of lymphocyte subset chemotaxis we have been able to show that TGF-beta can induce migration of both CD4+ and CD8+ T lymphocytes in vitro. This study provides further evidence that TGF-beta acts as a cytokine, being able to attract T lymphocytes and monocytes to sites of inflammation. Its role in the pathogenesis of inflammatory reactions is likely to be complex.

Cells, Cultured↗
PubMed1991

Does the infective agent of scrapie replicate without nucleic acid? An assessment.

The dogma of a unique status for the scrapie agent falling outside the virological spectrum is critically examined in the light of the circumstances which gave rise to it, and it is concluded that such an extreme view cannot be justified. The dogma arose in the first place by a combination of inadequate methodology and the lack of comparable data from other systems. It has been sustained partly by the same factors, and partly by a general failure to understand the impact on all relevant investigations of the exceptionally tenacious binding of infective agent to host-cell (membrane) components. This has not only greatly distorted the experimental findings, but as a consequence has resulted in extensive data misinterpretation. It is concluded that there is no hard evidence for the absence of a nucleic acid core in the scrapie agent so long as it is accepted that this is very small--i.e., of the order of 30 KDa (kilodaltons)--and is embedded within a cell membrane component matrix which protects it by forming a sequestered microenvironment: further that this is by far the simplest hypothesis.

Amyloidosis↗
PubMed1991

Central pontine myelinolysis in liver transplantation.

Five cases of central pontine myelinolysis (CPM) were detected by neuropathological examination in a series of 50 patients coming to necropsy after liver transplantation. One patient also had extrapontine myelinolysis. In no case was the diagnosis made during life. Only two patients showed rapid rises in serum sodium concentrations. The incidence of hyponatraemia, before and after transplantation, and rapid rises in serum sodium in patients with CPM was significantly greater than in the 45 patients showing no neuropathological evidence of CPM. It is concluded that there is a high incidence of CPM after liver transplantation, that clinical diagnosis is difficult, and that there is no simple direct correlation between rapid serum sodium changes and the development of this condition. Avoidance of major electrolyte fluctuations at the time of liver transplantation is recommended but it must be emphasised that CPM may occur without any rapid rise in serum sodium concentration.

Adolescent↗
PubMed1991

10 year review of invasive aspergillosis detected at necropsy.

Between 1980 and 1989, 32 cases of invasive aspergillosis were identified out of 2315 consecutive necropsies, an incidence of 1.4%. The incidence in immunosuppressed "high risk" patients was 10.7%. Twenty out of 32 cases showed spread beyond the lungs, with the brain the most common site. There was an increase in cases in the second half of the decade, attributable to the start of a liver transplantation programme. Liver transplant recipients and patients with haematological malignancies were at significantly greater risk of acquiring aspergillosis than kidney transplant recipients or those with solid malignancies treated with chemotherapy. There was also a greater risk of haematogenous dissemination in liver transplant recipients than in all other groups, and this was significantly associated with the use of high dose steroids as anti-rejection treatment. Aspergillus was isolated during life in only eight cases, which indicates a continuing need for and emphasises the value of necropsy.

Adolescent↗
PubMed1991

Increased expression of intercellular adhesion molecule 1 on bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis.

It has been suggested that immunological mechanisms involving lymphocyte-mediated damage are important in the characteristic bile-duct damage that occurs in primary biliary cirrhosis and primary sclerosing cholangitis. Because adhesion is necessary for the interaction of lymphocytes with their target structures, we have studied the expression of intercellular adhesion molecule 1, a ligand for the leukocyte adhesion receptor lymphocyte function-associated antigen 1 in the liver of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Strong expression of intercellular adhesion molecule 1 was seen on interlobular bile ducts and proliferating bile ductules in both conditions. In primary biliary cirrhosis, medium-sized ducts, which are spared by the disease, were negative. Minimal bile-duct staining was seen in conditions in which bile-duct damage is not a major feature, such as nonbiliary cirrhosis and acute liver diseases. In patients with cirrhosis from any cause, strong expression of intercellular adhesion molecule 1 was detected on the periseptal hepatocytes adjacent to new connective tissue. The intensity of immunohistochemical staining was recorded using a semiquantitative visual scoring system that was subsequently validated quantitatively by confocal laser scanning microscopy. The expression/induction of intercellular adhesion molecule 1 on bile ducts may be important in the pathogenesis of bile-duct damage in primary biliary cirrhosis and primary sclerosing cholangitis and is further evidence to support an immune pathogenesis in these two conditions. Furthermore, the induction of intercellular adhesion molecule 1 on hepatocytes may be an important factor in the liver-cell damage and fibrosis that occur during the development of cirrhosis.

Bile Ducts↗
PubMed1990

Neutrophil activation--an important cause of tissue damage during liver allograft rejection?

Although neutrophils have been implicated as mediators of tissue damage in a variety of conditions, their role in graft rejection has not previously been studied. Peripheral neutrophil activation was assessed sequentially in 16 patients following liver transplantation by measuring the ability of neutrophils to respond to the chemotactic peptide FMLP, to release superoxide radicals, and to cause extracellular proteolysis. All three functions increased 1-2 days before episodes of acute rejection and only returned to normal after treatment with high-dose corticosteroids. Three patients who did not develop rejection showed no increase in neutrophil function. Lymphocytes isolated from patients with acute rejection produced factors that were both chemotactic for and capable of activating normal neutrophils. This study shows that neutrophil activation occurs during acute liver allograft rejection, possibly in response to lymphokine secretion, and suggests an important, and hitherto unrecognized, mechanism of graft damage during rejection.

Adult↗
PubMed1990

Cerebral aspergillosis in liver transplantation.

Nine cases of cerebral aspergillosis were identified in a series of 44 brains obtained at necropsy from patients who had undergone liver transplantation. In two of these there was dual infection with Candida albicans. The primary focus of infection was invariably in the lungs. One case of pulmonary Aspergillus infection was found with no evidence of cerebral disease. Infection tended to occur in the period soon after transplantation, was associated with high dose steroids, retransplantation, and showed a significant seasonal incidence. Neurological findings were non-specific and only two cases were diagnosed before death. Aspergillus infection soon after transplantation indicates that this organism is a considerable nosocomial hazard, particularly in the winter and spring months. Positive cultures before death are rarely obtained and antifungal treatment should be started on clinical suspicion alone.

Adolescent↗