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Biomedical subjects

D H Adams

Publications and source records attributed to D H Adams.

At least 163 records · Page 9Linked to original sources
PubMed1993

Intercellular adhesion molecule-1 and MHC antigens on human intrahepatic bile duct cells: effect of pro-inflammatory cytokines.

Human intrahepatic biliary epithelial cells were isolated from the livers of patients with primary biliary cirrhosis and from normal livers and established in primary culture. The in vitro expression of intercellular adhesion molecule-1, HLA class I, and HLA class II on biliary epithelial cells was studied in response to tumour necrosis factor-alpha (0-500 U/ml), interferon-gamma (0-500 U/ml), and interleukin-1 (0-5 U/ml) by immunohistochemical staining and a semiquantitative scoring system validated by spectrophotometry and previously validated by laser confocal microscopy. The non-stimulated expression of intercellular adhesion molecule-1 and HLA class II was higher on cells derived from the primary biliary cirrhosis liver than on cells from normal liver, a difference not seen with HLA class I expression. A statistically significant increase in intercellular adhesion molecule-1 expression was seen with all three cytokines in cells derived from both primary biliary cirrhosis and normal liver. Increase in HLA class I expression was seen only with interleukin-1 5 U/ml for cells derived from both normal and diseased liver. Increase in HLA class II expression was seen only with interferon-gamma 500 U/ml for cells derived from diseased liver and with interleukin-1 5 U/ml for cells derived from both diseased and normal liver. These data show that pro-inflammatory cytokines increase expression of intercellular adhesion molecule-1, HLA class I, and HLA class II on human intrahepatic biliary epithelial cells in vitro and are consistent with the hypothesis that these locally acting factors may play a part in the pathogenesis of immune mediated disorders such as primary biliary cirrhosis in which immune mediated bile duct damage occurs.

Bile Ducts, Intrahepatic↗
PubMed1993

Aortic valve replacement in the elderly. Effect of gender and coronary artery disease on operative mortality.

BACKGROUND: Aortic valve replacement remains the treatment of choice for aortic valve disease, even in the extreme elderly who may present with advanced symptoms. Defining risk factors for short-term survival was the object of this study. METHODS AND RESULTS: This was a retrospective analysis of 717 patients at least 70 years of age who underwent aortic valve replacement alone or with coronary artery bypass graft between 1980 and 1992. Age range was 70 to 95 years, and mean age was 77 years; there were 529 septuagenarians (74%); 188 were octogenarians (26%); 326 were women (45%); and 386 patients (54%) had aortic valve replacement and coronary artery bypass graft. Atrial fibrillation/flutter or heart block was present in 16%, and 34% of patients were in New York Heart Association (NYHA) functional class IV. Aortic stenosis was present in 88%, and mechanical prostheses were used in 22% of patients. There were 47 deaths, giving an overall operative mortality of 6.6%, with 4.2% for aortic valve replacement and 8.8% for aortic valve replacement and coronary artery bypass graft (P = .01). The operative mortality for aortic valve replacement was 2.9% versus 10.3% for aortic valve replacement and coronary artery bypass graft in women (P = .006). The corresponding values for men were 5.6% and 7.4% (P = .31). Multivariate logistic regression showed coronary artery bypass graft and NYHA class IV to be significant predictors of operative mortality in women. The significant predictors in men were NYHA class IV, atrial fibrillation/flutter or heart block rhythm, and the use of mechanical prosthesis. Age was not a predictor of operative mortality in either sex. CONCLUSIONS: Aortic valve replacement carries an acceptable mortality rate in elderly patients. Female gender was a significant predictor of operative mortality in the concomitant coronary artery bypass graft group; however, gender was not a predictor of operative mortality in the isolated aortic valve replacement group. Advance stage of the disease process represented by NYHA class IV was a significant predictor of mortality for the whole group, stressing the need for earlier referral for surgery.

Aged↗
PubMed1993

Secretion of soluble chemotactic factors, including interleukin-6: a mechanism for the recruitment of CD8-positive T lymphocytes to human liver allografts during rejection.

In 35 patients receiving first liver transplants we assessed the chemotactic responsiveness of peripheral blood lymphocytes to bile, the subset composition of the responding population and the ability of peripheral blood lymphocytes to produce chemotactic factors. In 13 patients in whom acute rejection developed, lymphocyte chemotaxis in vitro was significantly greater in bile sampled 1 or 2 days after transplantation and before episodes of acute rejection than in bile sampled when rejection was clinically apparent or after steroid therapy during stable graft function. The chemotactic factors present showed preferential activity for CD8-positive T cells. Bile sampled during the same posttransplant periods from 11 patients who did not exhibit rejection showed significantly less chemotactic activity. In vitro cultured peripheral blood lymphocytes from patients in whom rejection developed produced lymphocyte chemotactic factors that induced a similar pattern of chemotactic responsiveness with preferential activity for CD8-positive T cells. Separate culture of purified CD4-positive and CD8-positive T cells obtained from patients in whom rejection developed showed that CD4-positive cells produced the factor(s). Analysis of the subset responses of normal peripheral blood lymphocytes to a variety of chemotactic cytokines showed interleukin-6 to have specificity similar to that observed with chemotactic bile, mixed peripheral blood lymphocyte culture supernatants and supernatants of CD4-positive T cells. Chemotactic activity was reduced by 45% to 90% in five chemotactic bile samples and three peripheral blood lymphocyte culture supernatants by treatment with affinity purified interleukin-6 monoclonal antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗