Interferons, properties and applications

The main theme of this thesis is the clinical evaluation of interferon. From the biology of the interferon system and animal experiments it can be expected that exogenous interferon will exert its optimum effect when used to prevent acute infections or to modulate chronic infections. Therefore, we administered interferon to patients with chronic hepatitis B virus infection (chapter 5) and to renal transplant recipients, in whom viral infections occur frequently in the first months after transplantation (chapter 6). The other studies in this thesis are directly related to the problems we met in the clinical studies. We wanted to study interferon in an animal renal transplantation model. For us the most obvious choice was the rat. However, little was known about the production and characterization of rat interferon. Chapter 2 describes our experiences with rat interferon. While we were well underway with the study in renal transplant recipients, we were contacted by Martin Hirsch, who was conducting a similar trial in Boston. Some of his patients receiving 3 x 106 U HLI every other day showed severe bone marrow depression. We had no such problem in our trial, but we used another type of interferon: HFI. For this reason we started a study on the t'oxicity of interferons for bone marrow in vitro

Poincar\'e and sl(2) algebras of order 3

In this paper we initiate a general classification for Lie algebras of order 3 and we give all Lie algebras of order 3 based on $\mathfrak{sl}(2,\mathbb C)$ and $\mathfrak{iso}(1,3)$ the Poincar\'e algebra in four-dimensions. We then set the basis of the theory of the deformations (in the Gerstenhaber sense) and contractions for Lie algebras of order 3.Comment: Title and presentation change

Construction of an isotropic cellular automaton for a reaction-diffusion equation by means of a random walk

We propose a new method to construct an isotropic cellular automaton corresponding to a reaction-diffusion equation. The method consists of replacing the diffusion term and the reaction term of the reaction-diffusion equation with a random walk of microscopic particles and a discrete vector field which defines the time evolution of the particles. The cellular automaton thus obtained can retain isotropy and therefore reproduces the patterns found in the numerical solutions of the reaction-diffusion equation. As a specific example, we apply the method to the Belousov-Zhabotinsky reaction in excitable media

Generalization of the Gell-Mann formula for sl(5, R) and su(5) algebras

The so called Gell-Mann formula expresses the Lie algebra elements in terms of the corresponding Inonu-Wigner contracted ones. In the case of sl(n, R) and su(n) algebras contracted w.r.t. so(n) subalgebras, the Gell-Mann formula is generally not valid, and applies only in the cases of some algebra representations. A generalization of the Gell-Mann formula for sl(5,R) and su(5) algebras, that is valid for all representations, is obtained in a group manifold framework of the SO(5) and/or Spin(5) group

Culture of graft-infiltrating cells from cryopreserved endomyocardial biopsies

Graft-infiltrating cells can be cultured from fresh endomyocardial biopsies (EMB) taken after heart transplantation to determine their growth patterns, phenotypic composition, and functional characteristics for clinical or scientific purposes. In this study we investigated whether graft-infiltrating cells can also be cultured successfully after cryopreservation of these EMB. Three different cryopreservation methods were used. One method gave successful growth in 100% of the cases (n = 6): The biopsy fragments were preincubated in 10% vol/vol dimethyl sulfoxide during 5 min at O°C, frozen to -70°C at approximately 1°C per minute, and subsequently immersed and stored in liquid nitrogen. Thawing was performed rapidly in water at 37°C. In addition, the effect of cryopreservation on cell surface phenotype and donor-specific cytotoxicity of these graft-infiltrating cells was analyzed. When compared to cultures of nonfrozen control biopsies, both qualities remained constant in most cases, although a variation in CD4+/CD8+ cell ratio was observed in 33% of these cultures. However, when nonfrozen fragments of size-matched biopsies were cultured separately, a similar variation in phenotype was noted, indicating that this phenomenon can be attributed to sampling variation and not to the cryopreservation procedure. The present findings suggest that it is no longer required to culture fresh (nonfrozen) post-transplant EMB to propagate graft-infiltrating cells: Culturing can be limited to cryopreserved EMB that are selected retrospectively, depending on actual clinical or scientific interests. Besides greatly facilitating the long-term monitoring of heart transplant recipients, this also means a substantial decrease in cost and work load for laboratories involved in heart transplantation

Living Donor Kidney Transplantation Should Be Promoted among "elderly" Patients

Background. Age criteria for kidney transplantation have been liberalized over the years resulting in more waitlisted elderly patients. What are the prospects of elderly patients on the waiting list? Methods. Between 2000 and 2013, 2622 patients had been waitlisted. Waiting time was defined as the period between dialysis onset and being delisted. Patients were categorized according to age upon listing: 64 years. Furthermore, the influence of ABO blood type and panel reactive antibodies on outflow patterns was studied. Results. At the end of observation (November 2017), 1957 (75%) patients had been transplanted, 333 (13%) had been delisted without a transplantation, 271 (10%) had died, and 61 (2%) were still waiting. When comparing the age categories, outflow patterns were completely different. The percentage of patients transplanted decreased with increasing age, while the percentage of patients that had been delisted or had died increased with increasing age, especially in the population without living donor. Within 6 years, 93% of the population 55 years, 39% received a living donor kidney, while >50% of patients without a living donor had been delisted/died. Multivariable analysis showed that the influence of age, ABO blood type, and panel reactive antibodies on outflow patterns was significant, but the magnitude of the influence of the latter 2 was only modest compared with that of age. Conclusions. "Elderly" (not only >64 y but even 55-64 y) received a living donor kidney transplantation less often. Moreover, they cannot bear the waiting time for a deceased donor kidney, resulting in delisting without a transplant in more than half the population of patients without a living donor. Promoting living donor kidney transplantation is the only modification that improves transplantation and decreases delisting/death on the waiting list in this population