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Biomedical subjects

D H Adams

Publications and source records attributed to D H Adams.

At least 181 records · Page 10Linked to original sources
PubMed1990

Changes in the expression of major histocompatibility complex class II antigens in liver allograft rejection.

The expression of major histocompatibility complex (MHC) class II antigens was studied in human liver grafts by immunohistochemical staining with monoclonal antibodies to HLA-DR, HLA-DP, and HLA-DQ antigens. Staining was carried out on frozen sections from 13 normal livers, used as controls, and 85 post-transplant specimens in six histological categories: acute rejection (n = 25); chronic rejection (n = 21); massive haemorrhagic necrosis (n = 2); resolving acute rejection (n = 10); non-rejection complications--pure cholestasis, ischaemia, biliary obstruction (n = 23); and stable graft function greater than 1 year post-transplantation (n = 4). Staining was graded semi-quantitatively on a scale of 0-3+ in bile ducts, hepatocytes, and vascular endothelium. Expression of class II antigens was increased in bile ducts, hepatocytes, and vascular endothelium in all of the post-transplant groups compared with controls. The degree of expression of HLA-DR and HLA-DP in bile ducts and vascular endothelium was significantly greater in cases of rejection than in the non-rejection groups. These observations suggest that increased class II antigen expression may be important in the pathogenesis of immune-mediated bile duct and endothelial damage in liver allografts. Immunohistochemical staining for class II antigens in post-transplant biopsies may also be useful as an adjunct to conventional histological diagnosis.

Antibodies, Monoclonal↗
PubMed1990

Bovine spongiform encephalopathy--a new disease transmissable to humans?

Current concerns about the cattle disease bovine spongiform encephalopathy do not appear to take cognisance of the parallel with scrapie, the similar/identical disease of sheep/goats. This has existed for 200 years, and clearly involved a longstanding consumption of meat/offal from affected animals, but apparently without consequential human disease. A summary is given of the characteristics of the human and animal spongiform encephalopathy diseases and their causative agents. The conclusion of the official Southwood Report that the bovine disease is caused by the inclusion of sheep scrapie material in cattle fodder is critically discussed: an alternative mechanism is proposed for its emergence.

Animals↗
PubMed1990

Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury.

Continuous intravenous infusion of heparin suppresses smooth muscle cell proliferation in rats after endothelial injury but may lead to hemorrhage and other complications. The anticoagulant property has been removed from chemically modified heparin without loss of antiproliferative effect but use of such compounds is still limited. In this study ethylene-vinyl acetate copolymer matrices containing standard and modified heparin were placed adjacent to rat carotid arteries at the time of balloon dendothelialization. After 14 days arterial occlusion by smooth muscle cell proliferation was defined. Matrix delivery of both heparin compounds effectively diminished this proliferation in comparison to controls without producing systemic anticoagulation or side effects. In addition, this mode of therapy appeared more effective than the administration of the same agents by either intravenous pumps or heparin/polymer matrices placed in a subcutaneous site distant from the injured carotid artery. Thus, heparin's inhibition of smooth muscle cell proliferation after vascular injury might be most effective within the microenvironment of the injured vessel wall, and the accelerated atherosclerosis or restenosis that often follows angioplasty and other vascular interventions might best be treated with site-specific therapy.

Animals↗
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

Inhibition of leukocyte chemotaxis by immunosuppressive agents. Specific inhibition of lymphocyte chemotaxis by cyclosporine.

Since chemotaxis is an important mechanism by which leukocytes are recruited to allografts during rejection, the effect of immunosuppressant agents on in vitro chemotactic responses of neutrophils, monocytes, and lymphocytes was studied. Cyclosporine caused profound inhibition of lymphocyte chemotaxis to three different chemotactic factors at pharmacologic levels but had no effect on neutrophil or monocyte chemotaxis. Methylprednisolone and azathioprine both inhibited chemotactic responses of neutrophils and monocytes as well as lymphocytes. These data suggest that immunosuppressant agents are potent inhibitors of leukocyte chemotaxis and that drugs differ as to which leukocyte cell type they inhibit. The selective action of cyclosporine might explain why this drug is ineffective in reversing established rejection episodes in which monocytes and neutrophils are also involved. Inhibition of leukocyte chemotaxis may be an important mode of action of immunosuppressant drugs, and drug regimes might be adjusted to cause selective inhibition of particular cell types.

Azathioprine↗
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↗
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

Patterns of leukocyte chemotaxis to bile after liver transplantation.

The role of chemotactic factors in the recruitment of leukocytes to human liver allografts was assessed by studying the effect of bile from transplant recipients on the chemotaxis of cells from normal subjects. Bile samples taken 2-3 days before clinical rejection were more chemotactic for lymphocytes than samples taken during rejection (p less than 0.01), during stable graft function (p less than 0.001), and from nontransplant patients (p less than 0.007). During clinical rejection there was an increase in bile chemotactic activity for both monocytes and neutrophils compared with samples from stable patients (monocytes: p less than 0.001; neutrophils: p less than 0.001) and nontransplant patients (monocytes: p less than 0.001; neutrophils: p less than 0.001). In serial studies chemotactic activity for lymphocytes reached a peak 1-3 days before the onset of clinical rejection, whereas maximum chemotactic activity for monocytes and neutrophils occurred at the time of rejection, when lymphocyte chemotaxis was decreasing. These results suggest that chemotaxis may be important in the recruitment of inflammatory cells to liver allografts and that chemotactic factors for lymphocytes, which appear in bile before clinical rejection, may be critical in the pathogenesis of rejection.

Bile↗
PubMed1989

Self-organisation and living systems: Is DNA an 'artificial intelligence'?

There seems little doubt that the maintenance and development of living systems is crucially dependent on an internal organisation of monumental complexity--particularly in higher living species. It is suggested that current thinking--particularly relating to the role of DNA in the total process cannot explain the underlying mechanisms and that a radical rethinking will be necessary. To this end it is proposed that DNA has a unique molecular electronic structure enabling it to operate as a computer analogue system for the highly efficient storage of information and as a type of artificial intelligence through which the information is translated and implemented to organise and control all aspects of the construction and activity of living systems.

Artificial Intelligence↗