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Biomedical subjects

J Milleck

Publications and source records attributed to J Milleck.

At least 19 recordsLinked to original sources
PubMed1992

Biological activity of mutants of human tumour necrosis factor-alpha.

Point mutations in different regions of the tumour necrosis factor-alpha (TNF-alpha) molecule influence anti-tumour cytotoxic/cytostatic activities as well as haemorrhagic tumour necrosis, tumour regression and lethal toxicity in mice. Mutations in the C-terminal region in positions 150 and 155 markedly decrease cytotoxicity for murine L929 fibroblasts and human MCF7 mammary carcinoma cells. Competitive binding experiments with 125I-labelled TNF-alpha revealed that the loss of cytotoxicity is caused by a loss of target cell binding. In contrast to the reduced activity against L929 and MCF7 cells, neither binding to nor cytostatic activity against the human myeloid leukaemia cell lines HL60 and U937 are affected. This target cell type-dependent behaviour is probably due to the fact that L929 and MCF7 cells express different types of TNF receptor compared with myeloid leukaemia cells. While a mutation in position 127 decreases the overall activity of TNF-alpha, a deletion of four N-terminal amino acids does not reduce biological activity. In vivo the TNF mutants differed in their anti-tumour effects and lethal toxicity, but a segregation of anti-tumour activity and toxicity was not observed.

Amino Acid Sequence↗
PubMed1986

Different E-rosetting properties of human peripheral blood NK- and K-cells.

Mononuclear, non-adherent blood leukocytes were separated into the spontaneously E-rosetting (E+) and non-E-rosetting (E-) fraction. NK- and K-cell activity was determined simultaneously in a 4 h assay against 51Cr-labeled K 562 cell line cells and rabbit antiserum coated mouse leukemia cells (Gr/E) respectively. In each case E- exhibited a significantly higher K-cell activity than E+ [M16 donors E-:E+ = 46 +/- 11:10 +/- 6 (% specific cytotoxicity)]. With regard to NK-cell activity E- of only 7 donors was significantly more active than E+ [M7 donors E-:E+ = 49 +/- 15:20 +/- 10]. Six times the activities of the two fractions were not significantly different [M6 donors E-:E+ = 46 +/- 15:39 +/- 14]. On the other hand E+ of 3 donors displayed a significantly stronger activity than E-[M3 donors E-:E+ = 13 +/- 10:36 +/- 9]. These results confirm the heterogeneity of NK-cells with respect to E-rosetting properties and indicate that NK- and K-cells of at least 3 donors may belong to different cellular subsets [NK:E- less than E+; K:E- greater than E+].

Animals↗
PubMed1982

[Human nonspecific killer cells].

The NK and K-cell activity of human leukocytes was investigated as compared with those cells of the K 562 cell line and murine cells covered by xenoantibodies in Graffi erythroblast leukaemia by means of the 51Cr release test. NK and K-cells could be identified in the blood and bone-marrow. However, they could not be identified in the thymus, lymph-nodes, and tonsils. Attempts of cell fraction with the blood of healthy donors revealed that the K-cells must be attributed to non-T-lymphocytes. NK-cells may be found in the fraction of non-T-lymphocytes as well as in that of T-lymphocytes. Killer cell activity tests in children with acute leukaemia resulted in leukaemia cells having NK and K-cell activity only in very rare cases. ALL patients in remission had strongly lowered NK-cell values under chemotherapy. In comparison to that, chemotherapy had no influence on K-cell activity. On the one hand, NK-cell activities were induced in mixed cultures of allogenous lymphocytes of the blood and, on the other hand, in cells of lymph-nodes. Attempts of fractionation, investigations for determining the influence of chemotherapy and attempts of inducing killer cell activity in vitro lead to the conclusion that NK and K-cells may be regarded as similar cell populations, being, however, not identical.

Acute Disease↗
PubMed1982

Winding anomalies in nuclear DNA from malignant cells. I. Experimental evidence.

The superhelical properties of nuclear DNA from malignant cells of human origin (leukemic cell lines Reh and D-562, mesothelioma cell line, and peripheral blood monocytes from acute monocytic leukemia) were investigated in neutral sucrose gradients with ethidium bromide. As compared with the universal superhelical density of nuclear DNA from normal cells, the DNA released from malignant cells showed a substantially higher negative superhelix content, equivalent to an increased deficiency in right-handed DNA duplex turns. In regard to analogous results obtained from other malignant cell systems, the extremely underwound structural state of nuclear DNA appears to be a feature common to malignant cells.

Cell Line↗
PubMed1980

[Subtypification of acute lymphocytic leukaemia (ALL) in childhood by characterization of immunological surface membrane markers (author's transl)].

Leukaemic blast cells isolated from bone marrow or blood of 42 children with ALL were investigated for presence of immunological surface membrane markers. By characterization of 5 surface markers (reaction with an anti-ALL serum for demonstration of a leukaemia-associated antigen, reaction with an anti-thymocyte serum and formation of E-rosettes for demonstration of T-lymphozytes, as well as reaction with an anti-Ig serum and formation of EAC-rosettes for demonstration of B-lymphocytes) the ALL cells of the 42 patients could be divided into 5 subtypes: I. 18 patients (42,7%( O-ALL with common ALL antigen II. 13 patients (31%) O-ALL without common ALL antigen III. 7 patients (16,7%) T-ALL with E-rosette formation IV. 3 patients (7,2) T-ALL without E-rosette formation V. 1 patients (2,4%) B-ALL.

Adolescent↗
PubMed1979

Human leukaemia-associated antigens expressed by acute myelocytic leukaemia cells and their detection by heterologous antisera.

Antisera against human acute myelocytic leukaemias were tested in complement-dependent in-vitro cytotocity tests against leukaemia cells and normal cells as targets. After absorption with erythrocytes and spleen cells from allogeneous donors the antisera reacted with leukaemia cells, but not with leukocytes from bone marrow and the peripheral blood of children in remission, lymphocytes from healthy donors, enriched B-lymphocytes, enriched T-lymphocytes, PHA-induced blasts and cord blood lymphocytes. Extensive cross reactions were obtained in the tests against leukaemia cells. The antisera reacted not only with AML cells, but also with ALL, CLL, and CML cells. It was possible to remove the cross-reactivity with ALL cells through absorption with ALL cells or with fetal tissue, and to remove the cross reactivity with CLL cells through absorption with CLL. A complete absorption of the anti-AML sera was possible with AML and CML cells. After absorption with fetal tissue and CLL cells the antisera showed exclusively specificity for myelocytic leukaemias. Thus, AML cells contain three leukaemia-associated membrane antigen components: an antigen of fetal origin, a "CLL-specific" antigen, and an antigen that occurs on myelocytic leukaemias.

Adult↗
PubMed1979

Human leukaemia-associated antigens expressed by acute lymphocytic leukaemias and their detection with heterologous antisera to T, B-, and non-T-non-B subtype AL blasts.

Antisera from rabbits and goats against subtypes of acute lymphocytic leukaemia (ALL with T-cell markers, ALL with B-cell markers, Non-T-non-B ALL) were tested for their specificity in complement-dependent in-vitro cytotoxicity testing. After absorption of the fivefold diluted antisera with erythrocytes and spleen cells of allogenous donors they reacted with ALL cells, but not with leukaemias of other types (AML, CLL, CML), lymphocytes of healthy donors, enriched B-lymphocytes, enriched T-lymphocytes, PHA-stimulated lymphocytes, cord lymphocytes and bone marrow lymphocytes of patients in remission. In the reactions of the antisera against ALL cells the subtype of ALL is of major importance: Six rabbit antisera and one goat antiserum against T-subtype ALL reacted in all 19 tests with the leukaemia cells of 5 patients with T-cell ALL and in all 9 tests with thymocytes of 3 donors, but only in 14 out of 41 tests with the leukaemia cells of 14 Non-T-non-B ALL patients. One antiserum against a B-subtype ALL lysed B-cell ALL (1/1), but not T-cell ALL (0/3), Non-T-non-B-cell ALL (1/5) and thymocytes (0/2). Four antisera against Non-T-non-B-subtype ALL reacted in 22 out of 46 tests with the Non-T-non-B cells of 17 ALL patients, but did not react with the leukaemia cells of 4 children with T-cell ALL (0/16), one child with B-cell ALL (0/1) thymocytes of 2 donors (0/4). The reactions of the anti-ALL sera with fetal liver cells, complete absorbability of the antileukaemic activity of the antisera with fetal tissue and the reactions of an anti-fetal serum with ALL cells point to the existence of fetal antigen components as leukaemia-associated antigens.

Adolescent↗
PubMed1978

[Foetal antigens on leukaemia cells (author's transl)].

An antiserum against human foetal liver cells reacted in in-vitro-cytotoxic test with the leukaemia cells of 6 out of 10 children with acute lymphocytic leukaemias (ALL) and with the lymphoma cells of 1 out 2 children with lymphosarcoma (LS). No cytotoxic reactions were obtained against leukaemia cells of 5 children with acute myelogenic leukaemia (AML), leukaemia cells of 7 adults with chronic lymphocytic leukaemia (CLL), bone marrow cells of 9 children in clinical remission and lymphocytes of normal donors. The cytotoxic activity of the anti-foetalserum was removed by absorption with foetal liver but not with adult liver. The results suggest that foetal antigens may occur on ALL-cells and LS-cells.

Adult↗
PubMed1978

[Complement activity in leukemic patients].

The in vitro test of heterologous anti-leukaemic sera against human leukaemic cells resulted in the serum of leukaemic patients being able to produce a lysis of leukaemic cells in the leukaemic phase as well as in remission when specific heterologous antibodies were present.

Antibody Specificity↗
PubMed1978

Specificities of heterologous antisera against human leukaemia cells. 1. Reactions against leukaemia cells.

Rabbit or goat antisera directed to ALL, CLL, AML and CML cells were investigated in cytotoxicity tests with different leukaemia and normal cells as targets. After absorptions with erythrocytes and spleen cells from allogeneic donors the antisera killed only leukaemia cells. There was no reaction with remission leukocytes or blood leukocytes from normal donors. Anti-ALL-Sera reacted in 35 out of 49 tests with ALL cells from 13 patients. Apparently the ALL antisera which were directed to the T cell subtype of ALL preferentially affected ALL cells of this subtype. Cross reactions with cells from CLL, AML and CML were not found. Anti-CLL-sera reacted in 10 out of 12 tests with CLL cells from 4 donors, and in 4 out of 20 tests with ALL cells from 7 donors and also with the cells of a CML patient. AML cells from two patients were not killed. Antisera against AML and CML showed extensive cross reactions with cells of myelocytic and lymphocytic leukaemias. Absorption tests demonstrated the presence of two antibody specificities in AML antisera, one of which being directed to a common antigen of AML and ALL cells and another against an antigen of myelocytic leukaemia cells.

Antibodies, Neoplasm↗
PubMed1978

Specificities of heterologous antisera against human leukaemia cells. 2. Reactions against fetal liver cells and absorption studies with fetal tissue.

Rabbit or goat antisera directed to ALL and AML cells were investigated in cytotoxicity tests with fetal liver cells as targets. After absorption with erythrocytes and spleen cells from allogenic donors the antisera killed fetal liver cells. There was no reaction with remission leukocytes or blood leukocytes from normal donors. Treatment with fetal tissue removed the activity of the AML and ALL antisera against ALL cells but not of the AML antisera against AML cells. This indicates the existence of at least two antigens on the surface of AML cells, one antigen is common with ALL cells and of fetal origin and another one seems to be characteristic of AML cells and not of fetal origin. Because treatment with fetal tissue removed all activity of the ALL antisera it can be assumed that leukaemia-associated antigens on ALL cells are of fetal origin.

Antibody Specificity↗
PubMed1975

[On the mode of action of heterologous antileukemic sera. Growth of syngeneically transplanted leukemia cells on serum treated neonatally thymectomized mice (author's transl)].

A heterologous antiserum against a Nitrosomethylurea--induced mouse leukemia prevented the outgrowth of syngeneically transplanted leukemia cells in neonatally thymectomized mice. After subcutaneous challenge with 50 000 leukemia-ascites cells thymectomized CBA mice at the age of 8 weeks were given 5 intraperitoneal injections each of 0,1 ml of the heterologous serum. While the antileukemic serum protected 9 out of 11 mice all of the 11 mice treated with normal rabbit serum developed a tumor. The absence of the thymus was confirmed by macroscopic control and by the absence of antibodies against the injected rabbit serum. With regard to previous findings showing a cooperation of heterologous antibodies with host cells as responsible for the antileukemic effect this result indicates that the effector cells are thymus-independent.

Animals↗