Buurman, W.A.

Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies (Article)

2013-02-01T00:00:00Z

Background Enterocyte damage is the hallmark of coeliac disease (CD) resulting in malabsorption. Little is known about the recovery of enterocyte damage and its clinical consequences. Serum intestinal fatty acid binding protein (I-FABP) is a sensitive marker to study enterocyte damage. Aims To evaluate the severity of enterocyte damage in adult-onset CD and its course upon a gluten-free diet (GFD). Furthermore, the correlation among enterocyte damage, CD autoantibodies and histological abnormalities during the course of disease is studied. Methods Serum I-FABP levels were determined in 96 biopsy-proven adult CD patients and in 69 patients repeatedly upon a GFD. A total of 141 individuals with normal antitissue transglutaminase antibody (IgA-tTG) levels served as controls. I-FABP levels were related to the degree of villous atrophy (Marsh grade) and IgA-tTG. Results I-FABP levels were elevated in untreated CD (median 691 pg/mL) compared with controls (median 178 pg/mL, P < 0.001) and correlated with Marsh grade (r = 0.265, P < 0.05) and IgA-tTG (r = 0.403, P < 0.01). Upon a GFD serum levels decreased significantly, however, not within the range observed in controls, despite the common observed normalisation of IgA-tTG levels and Marsh grade. CD patients with elevated I-FABP levels nonresponding to GFD showed persistent histological abnormalities. Conclusions Enterocyte damage assessed by serum I-FABP correlates with the severity of villous atrophy in coeliac disease at the time of diagnosis. Although enterocyte damage improves upon treatment, substantial enterocyte damage persists despite absence of villous atrophy and low IgA-tTG levels in the majority of cases. Elevated I-FABP levels nonresponding to gluten-free diet are indicative of histological abnormalities and warrant further evaluation.

Kidneys from donors after cardiac death provide survival benefit (Article)

2010-06-01T00:00:00Z

The continuing shortage of kidneys for transplantation requires major efforts to expand the donor pool. Donation after cardiac death (DCD) increases the number of available kidneys, but it is unknown whether patients who receive a DCD kidney live longer than patients who remain on dialysis and wait for a conventional kidney from a brain-dead donor (DBD). This observational cohort study included all 2575 patients who were registered on the Dutch waiting list for a first kidney transplant between January 1, 1999, and December 31, 2004. From listing until the earliest of death, living-donor kidney transplantation, or December 31, 2005, 459 patients received a DCD transplant and 680 patients received a DBD transplant. Graft failure during the first 3 months after transplantation was twice as likely for DCD kidneys than DBD kidneys (12 versus 6.3%; P = 0.001). Standard-criteria DCD transplantation associated with a 56% reduced risk for mortality (hazard ratio 0.44; 95% confidence interval 0.24 to 0.80) compared with continuing on dialysis and awaiting a standard-criteria DBD kidney. This reduction in mortality translates into 2.4-month additional expected lifetime during the first 4 years after transplantation for recipients of DCD kidneys compared with patients who await a DBD kidney. In summary, standard-criteria DCD kidney transplantation associates with increased survival of patients who have ESRD and are on the transplant waiting list. Copyright

Involvement of T cells in enhanced resistance to Klebsiella pneumoniae septicemia in mice treated with liposome-encapsulated muramyl tripeptide phosphatidylethanolamine or gamma interferon (Article)

1998-01-01T00:00:00Z

We have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-gamma) results in strongly increased survival of mice from a normally lethal septicemia with Klebsiella pneumoniae. It was anticipated that the treatment acts on macrophages and nonspecifically augments host resistance to various infections. In the present study, we provide evidence for a key role for T cells in host defense potentiation by the liposomal immunomodulators toward K. pneumoniae septicemia. It is shown that both CD4 and CD8 cells are important in immunomodulation, most likely due to production of IFN-gamma. Depletion of circulating IFN-gamma resulted in strong reduction of the antimicrobial host defense activation. Administration of interleukin-10 resulted in decreased antimicrobial host defense activation by liposomal immunomodulators. Moreover, administration of liposomal immunomodulators was shown to induce predominantly T-helper type 1 (Th1) cell populations in the spleen. These findings indicate that immunomodulation with liposomal MTPPE and IFN-gamma favors Th1 and NK cell activation.

Genetic resistance to bone marrow transplantation (Doctoral Thesis)

1976-12-08T00:00:00Z

The homeostasis of several tissues is maintained by a process of proliferation and differentiation to replace the cells which are constantly lost. The most undifferentiated cells of a certain tissue, capable of proliferation and differentiation, are stern cells. Stem cells have "the capacity for extensive proliferation, resulting in renewal of its own kind as well as giving rise to fully differentiated cells" (Caffrey-Tyler and Everett, 1966). In multicellular animals various types of stem cells can exist in a more or less differentiated form. In the most primitive multicellular organisms, the parazoa, any cell type is capable of proliferation and differentiation into the different cell types which form the organism. In these organisms each cell can be considered as a stem cell. Among higher classified animals, Planarians (Platyhelminthes) are known for their enormous capacity to regenerate. These flatworms carry an omnipotent stem cell called neoblast. Different techniques were used to prove that neoblast population forms a stem cell pool which can differentiate into any cell type of the animal in case of a spontaneous fissure of the animal or a healing process after a trauma (cf. BrQ\ndsted, 1969). Recent radiobiological studies produced suggestive evidence that the survival of planarians after irradiation is dependent on the presence of one single cell population (Lange, 1968a, b). This evidence is in favour of the neoblast concept, but could also be in favour of the concept which attributes the regeneration to dedifferentiation of differentiated cells. In vertebrates various types of stem cells have been found. Cell renewal systems in these animals are generaUy restricted to tissues with relatively short living cells. Cell renewal systems are also found in other tissues and have a function in repair of local injuries. This latter type of repair seldom results in remodeling of the original form of the injured tissue. Among the vertebrates only the Urodele amphibians (Caudata) show a .complete regeneration of an injured or amputated limb or taiL Most authors assume that this regeneration is not dependent on stem cells1 but on dedifferentiation of differentiated cells (cf. de Both, 1969). The most active cell renewal systems are those which produce ceHs, that have a relatively short life time when compared with the life span of the individual. Examples of these cell renewal systems are among others the hemopoietic system, the epithelia of the skin, the gastro-intestinal tract and the urogenital system.