[Histones significance in cell differentiation and genetic control].
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Animals↗
Biomedical subjects
T Kristensen
Publications and source records attributed to T Kristensen.
The presence and possible role of phosphopantothenic acid in gramicidin S synthetase.
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Journal Article↗
Effects of niacin therapy that simulate neoplasia: hepatic steatosis with concurrent hepatic dysfunction.
Niacin, a widely used antihyperlipidemic agent, can produce hepatic steatosis and clinical hepatic abnormalities that together simulate the presentation of hepatobiliary neoplasia. We describe a patient initially suspected of having hepatobiliary neoplasia for whom imaging studies played a pivotal role in reaching the correct diagnosis of niacin-induced hepatotoxicity. Radiologists should become knowledgeable of these niacin-related effects, add niacin effects to the differential diagnosis of hepatic steatosis, and understand the value of correlative imaging in distinguishing these effects from hepatobiliary neoplasia.
Chemical and Drug Induced Liver Injury↗
Proliferative response of human T lymphocytes to porcine fetal brain cells.
Intracerebral grafting of porcine fetal brain cells is a potential treatment of neurodegenerative disorders in humans. Although it is well known that the survival of fetal pig brain cells in the rat brain requires immunosuppression, the response of human T lymphocytes to fetal pig brain cells is unknown. Here we report on the proliferative response of human T lymphocytes to freshly isolated cells and 14-18 days cultured cells from 28- or 35-day-old porcine fetal brains. After 5 days of mixed lymphocyte-brain cell culture, we observed no or only minor T cell responses to the freshly isolated brain cells, while both CD4 cells and CD8 cells proliferated in response to the cultured brain cells. Pretreatment of the cultured brain cells with heat-inactivated human serum significantly reduced the proliferative T cell response. The data suggest that the porcine fetal brain contains cells that can stimulate the human cellular immune system, and that this stimulation may be reduced by pretreatment of the fetal pig brain cells with human serum.
Animals↗
Immunisation of colorectal cancer patients with autologous tumour cells.
Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression of immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled the criteria for inclusion. No serious side effects were observed. With three years of observation time, two patients are healthy, while the rest have had recurrence, and two of them have died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80. There was an inverse relation between survival and HLA class II expression. This highlights an essential problem, in the absence of CD80 expression the expression of HLA class II may induce anergy. In future attempts to develop improved vaccines this problem should be addressed.
Adenocarcinoma↗
Neural xenotransplantation: pretreatment of porcine embryonic nigral tissue with anti-Gal antibodies and complement is not toxic for the dopaminergic neurons.
The immunogenicity of porcine tissue is a major obstacle to its use as donor material in xenotransplantation for neurodegenerative diseases. We are currently evaluating a novel strategy for reducing the immunogenicity, in which the alpha-galactosyl epitope (Galalpha1,3Galbeta1,4GlcNAc-R) is used as a target for antibody- and complement-mediated removal of microglia. In the present study, our aim was to determine whether a pretreatment with antibodies against the alpha-galactosyl epitope (anti-Gal) and complement would lyse or otherwise damage dopaminergic neurons in porcine embryonic ventral mesencephalon (VM), the donor tissue for treatment of Parkinson's disease by xenotransplantation. Cell suspensions prepared from VM tissue from 27-day-old pig embryos were incubated with anti-Gal, purified from normal human serum by affinity chromatography, or medium only (control), and subsequently with rabbit complement. After these pretreatments, the cell suspensions were transplanted into the right striatum of 14 adult rats (two groups of 7 animals). The animals were sacrificed 20 days after transplantation, the brains were processed for histology, and the sections were stained for Nissl substance, porcine neurofilament, tyrosine hydroxylase, and rat CD45 to determine graft volume, presence of porcine neurons, content of dopaminergic cells, and leukocyte infiltration, respectively. The VM tissue pretreated with anti-Gal and complement gave rise to dopaminergic grafts that were indistinguishable from those derived from VM tissue given the control pretreatment. In 5 of the 14 animals, the grafts were infiltrated by host leukocytes, but in two of these recipients, the infiltration was only minimal. We conclude that anti-Gal and complement can be applied to porcine embryonic VM tissue without damaging the dopaminergic neurons and their precursors.
Animals↗
Direct cell mediated lympholysis in man. Cellular cytotoxic capacity of 100 normal, healthy blood donors.
The cellualr lymphocytotoxic capacity of 100 normal, healthy blood donors were investigated by the Direct Cell Mediated Lympholysis (DCML) test. The scorings were found to be distributed according to the normal, exhibiting a mean value of 0.1 Cr-51 release %, and an upper 1% significance level of 10.1 release 1%. It is concluded that lymphocytes from the peripheral blood of blood donors may well be used as negative biological controls in DCML testing of immunologically primed patients (e.g. after allotransplantation).
Blood Donors↗
Direct cell mediated lympholysis by peripheral blood lymphocytes from renal allograft recipients.
Investigations of 22 kidney allograft recipients by the Direct CML-test revealed coincidence between acute allograft rejection and a positive test. 15 patients exhibited acute rejection, 3 chronic, and 4 no rejection episodes. 4 patients with acute rejection were not detected as positive in Direct CML, while 3 patients were positive without acute rejection, one having a chronic rejection. The exact role of HL-A antigens for the specificity of a positive Direct CML could not be evaluated from this material. It is concluded that the Direct CML-test may be helpful for the diagnosis of acute rejection, but that it has only limited power as the only test of recipients' response to foreign tissue.
Acute Disease↗