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Biomedical subjects

P Ebbesen

Publications and source records attributed to P Ebbesen.

At least 19 recordsLinked to original sources

Elevated titer of antibodies to Simian sarcoma virus envelope antigen (gp70) and normal response to influenza virus in untreated Danish Hodgkin's patients.

Untreated Danish Hodgkin's disease (HD) patients and paired age- and sex-matched controls were tested for serum antibodies to Epstein-Barr virus (EBV), six strains of influenza virus and Simian sarcoma virus/Simian sarcoma-associated virus [SSV(SSAV)] antigens. HD sera showed significantly elevated titers against EBV and both increased incidence and mean titer of antibodies to the envelope glycoprotein of SSV(SSAV), whereas testing against the influenza viruses revealed no differences between HD and controls. A focus reduction assay demonstrated a low incidence in HD and controls of sera with neutralizing effects against SSV(SSAV) and the "baboon" C-type virus component of the human HL-23 virus complex, which seemed coupled to HL-A type W19.

Antibodies, Viral

Natural polyclonality of spontaneous AKR leukemia and its consequences for so-called specific immunotherapy.

Young female AKR mice made leukemic by iv inoculation of 10(3) spontaneous AKR thymoma cells were treated with repeated injections of irradiated cells from the same tumor. Treatment began 1 day after injection of the viable cells. The cytotoxicity of sera and lymphoid cells from healthy mice immunized with lymphoma cells from either treated or nontreated mice with leukemia grafts revealed that the tumor cells could be subdivided into four distinct antigenic types. One type (clone A) accounted for about 97% of the lymphoma cells in each mouse with spontaneous leukemia, whereas the remaining 3% were subdivided into three other distinct antigenic types (clones B, C, and D). Lymphoma cells from treated mice with grafted leukemia were never clone A type but either clone B, C, or D type. Repeated sc injections of 10(7) irradiated cells from spontaneous AKR thymomas induced from 15 to 34% cure in mice with grafts of leukemia cells. Treatment with only clone A induced about 32% cure, whereas treatment with clone B, C, or D had no beneficial effect. Treatment with 10(7) cells each of clone A plus clone B gave 33% cure; clone A plus clone B plus clone C, 45%; and all four clones cured 92% of the mice with leukemia grafts. The efficiency of immunotherapy may be influenced by the natural clonality of the tumor to be treated.

Animals

Arrest of cell membrane movements by in vitro incubation with polycation reversed by polyanion.

A total arrest of cell membrane movement occurred after incubation for 2 h of cultured fibroblasts with the polycation DEAE-dextran. The immobilized cells resumed normal membrane undulations after exposure for 5 min to the polyanion dextran-sulphate. The influence of DEAE-dextran on the electrophoretic mobility, which was seen after 10 min of incubation was also erased by a subsequent incubation with dextran-sulphate. No influence on growth of the culture was seen.

Animals

Immunoadjuvant treatment of primary grafted and spontaneous AKR-leukemia. I. Treatment efficiency correlated to autoimmune reactivity.

Young AKR mice grafted i.v. with 10(1) or 10(3) cells from spontaneous AKR thymomas were treated with repeated i.v. injections of BCG or subcutaneous injections of irradiated AKR thymoma cells. BCG often cured mice from graft leukemia, whereas the effect of irradiated thymoma cells was less effective. Mice that did not develop graft-leukemia after graft of 10(1) leukemia cells and BCG treatment showed a spontaneous leukemia in 30% of the cases later. Ninety percent of nongrafted mice developed spontaneous leukemia whether BCG-treated or not. General immune reactivity as assessed in individual mice by T and B lymphocyte mitogen tests as well as the hemolytic plaque-forming cell assay had no clear correlation to the effects of immune adjuvants in respect to survival. In contrast, occurrence of self-directed immune reactions were clearly correlated to survival and cure of grafted and BCG-treated mice as revealed by assays both in vitro and in vivo. However, 13 to 25% of the mice apparently cured of leukemia developed a wasting-like syndrome that sometimes terminated in death. The immplications of self-directed immune reactions as mediators of the anti-neoplastic effects of immunoadjuvants.

Adjuvants, Immunologic

Life span, leukaemia and amyloid incidences of untreated and polycation-treated AKR mice.

AKR mice, which have a short mean survival time and usually die with leukaemia, were studied from one month of age for correlation between these two parameters. For untreated animals we found the same mean survival time whether or not leukaemia occurred. By treating sucklings with the polycations diethylaminoethyl-dextran or hexadimethrine bromide the leukaemia incidence was significantly reduced. However, the mean survival time was unchanged, and remained the same in leukaemic and non-leukaemic animals. It is therefore suggested that the early death of AKR mice results from an ageing process and does not require leukaemia for implementation. Our prophylactic polycation treatment was furthermore found to induce spleen amyloid in some but not all of the mice that remained non-leukaemic.

Aging

Specificity of the inhibition of DNA synthesis by extracts from cloned normal, sarcoma-virus-transformed and revertant 3T3 cells.

Extracts containing tissue-specific DNA-inhibitory activity were prepared from normal FL (Swiss) and BALBc3T3 cells, from these cells transformed with sarcoma virus and from revertants cloned from the transformed cell lines. By testing all extracts on all cell lines we found that (1) production of and susceptibility to the inhibitors were decreased in transformed BALB/c cells (2) specificity varied with expression of the transforming genome, as an extract from a given cell line inhibited the growth of its cell of origin, e.g. revertant, more than normal or transformed cells, and (3) there was also a DNA-synthesis stimulator.

Animals

Effect of tissue specific mitotic inhibitors on survival time of spontaneous and virus-induced murine leukaemia and influence on myocardial degeneration.

Treatment of adult AKR mice with tissue-specific mitotic inhibitor mol. wt. 1,000--20,000 extracted from the AKR thymus significantly delayed the onset of spontaneous thymus leukaemia, whereas extracts of other organs were without effect. A slight prolongation of survival time was found with spleen extract when administered to BALB/c mice infected with Rauscher virus, which causes leukaemia starting in the spleen. Thymus extracts of MW 100,000--300,000 caused myocardial degeneration in some leukaemic and nonleukaemic mice.

Animals

Correlation between polyion effect on cell susceptibility to in vitro infection with murine C-type viruses and polyion effect on some membrane-related functions.

Polyions were tested for effects on some membrane-related functions. Both polycations investigated reduced the negative surface charge of assay cells and enhanced in vitro infectivity of murine C-type viruses, but had no influence on leukemia-virus-induced XC cell syncytia formation. Three polyanions increased the net outer cell charge, while only one of four inhibited infectivity and two of three impeded syncytia formation. Polyions had a slight, probably toxic, effect on the transmembrane potential, independent of their charge. Cells treated with fluorescent DEAE-dextran showed diffuse staining, which 4 h later had been modified into a granular fluorescence with unstained areas now present. This change correlated with a loss of enhancement of viral infectivity. The only polyanion which inhibited viral infectivity had a strong antihyaluronidase activity, and hyaluronidase and Ca++ both increased viral infectivity. It is suggested, therefore, that polyions may in part work on virus-cell membrane interactions by influencing membrane enzymes and not necessarily by simply changing the net outer cell surface charge.

Cell Line

Experimental induction of tumor growth control by immune adjuvants: current status and some theories to be explored.

Immune adjuvants have been shown to induce tumor growth control in many experimental tumor-host models. The beneficial effect depends on tumor size and type and dose of the adjuvants in question, but few experimental data elucidate, which immunological mechanisms--if any--that are directly involved in the tumor destructive processes induced by immuno-adjuvants. The importance of non-specific tumor immunity is discussed with emphasize on the importance of immuno-competent cells that react non-specifically, and that may include "self-directed" cells. Non-immunological mechanisms are proposed also to be of importance, underlining the possible role of the phenomenon of spontaneous reversion of malignant cells to a non-malignant state. It is finally stressed that both immunologic and non-immunologic properties of immunoadjuvant induced tumor growth control must be analysed before therapy with immunoadjuvants can be optimally applicated in the cancer patient.

Adjuvants, Immunologic

A case control study on immunity to two Epstein-Barr virus-associated antigens, and to herpes simplex virus and adenovirus in a population-based group of patients with Hodgkin's disease in Denmark, 1971-73.

One hundred and eighty-five patients with untreated Hodgkin's disease (HD) comprising 86% of all new cases diagnosed in Denmark over a 2-year period, were individually matched with healthy controls of the same age, sex, and social class. In comparison to controls, HD patients showed significantly elevated mean antibody titres to Epstein-Barr viral capsid antierences in mean titres were found for adenovirus common antigen. Subdivision of the patients by age, sex, social class, HL-A antigens, stage of disease and histology did not alter this pattern, except that significant case-control differences in EB-VCA titres could be demonstrated only for the nodular sclerosis and lymphocyte predominance subgroups. After 1 year of treatment, a significant rise in EB-VCA mean titre had taken place. Splenectomy seemed to promote this titre elevation. Neither the initial titres to EB-VCA and EBV-EA nor changes in titres over time were related to prognosis. The results of our study, which are more representative of a population of HD patients and controls than previously reported studies, confirm that the reported relationship between EBV and HD exists, but that the elevated EBV titres are probably not of etiologic significance in most HD patients.

Adenoviruses, Human

Effect of age of non-skin tissues on susceptibility of skin grafts to 7,12-dimethylbenz[alpha]anthracene (DMBA) carcinogenesis in BALB/c mice, and effect of age of skin graft on susceptibility of surrounding recipient skin to DMBA.

The influence of age-dependent alterations in non-skin tissues on chemical carcinogen-induced skin papilloma development was studied by treatment with 7,12-dimethylbenz[alpha]anthracene (DMBA) of 4-month-old skin grafts sewed onto 4- and 20-month-old syngeneic recipients. Skin of 4- and 20-month-old BALB/c female mice differed in susceptibility to DMBA carcinogenesis, but the 4-month-old grafts showed the same papilloma incidence independent of the age of the recipient mice. In a different experiment, the influence of age of skin grafts on papilloma development on DMBA-treated recipient skin was studied. Fourteen- and 26-month-old skin grafts were carried by 14-month-old recipients. Grafts of those two ages are known to differ in susceptibility to DMBA carcinogenesis, but no effect of the grafts on papilloma development on DMBA-treated recipients was detectable. It was concluded that certain age-dependent differences in skin susceptibility to chemical carcinogens are solely a reflection of alterations in the skin at the site of carcinogen treatment.

9,10-Dimethyl-1,2-benzanthracene