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Biomedical subjects

T T Timonen

Publications and source records attributed to T T Timonen.

12 recordsLinked to original sources
PubMed1993

Bacillus Calmette-Guérin sensitises fresh transitional carcinoma cells and T24 cell line to non-MHC-restricted cytotoxicity in vitro.

The activity of lymphokine (interleukin-2) activated killer (LAK) cells from 9 patients with transitional cell carcinoma (TCC) was tested against autologous, freshly purified transitional carcinoma cells. Cytotoxicity was relatively low. Bacillus Calmette-Guérin (BCG) substantially augmented both LAK activity and the cytolytic activity of non-stimulated peripheral blood mononuclear cells (PBMC) against autologous TCC when tested with 6 additional TCC patients. A similar enhancing effect of BCG was noted with leucocytes obtained from normal donors when tested against an allogenic T24 cell line. Both natural killer (NK) cells and T cells appeared to be responsible for the increased cytolytic activity caused by BCG. No cytolytic activity was noted against normal transitional epithelial cells. Sensitisation of TCC cells to the immune system may explain the clinical effects of BCG.

Antigens, Bacterial↗
PubMed1992

Therapeutic effect of heme arginate in myelodysplastic syndromes.

In order to investigate, whether heme would induce a response in myelodysplastic syndromes (MDS), 14 symptomatic patients (4 RA, 3 RARS and 7 RAEB) were treated with infusions of heme arginate 3 mg/kg body weight on 4 consecutive days, mostly for six cycles at 2-week intervals. Three of 14 patients (21%) showed an improvement in anemia (97-152, 79-120 and 92-114 g/l) within a few weeks, and 1 showed a milder increase in hemoglobin level (102-118 g/l). Of the 2 responders with marked thrombocytopenia, 1 showed an improvement in the platelet count (7-37 x 10(9)/l) and her regular need for red cell and platelet transfusions ceased. Some regression in bone marrow (BM) cytology was seen in all 3 responders. One of the responders is still in remission 41 months after cessation of the treatment, while in the other 2 the response lasted for 26 and 5 months. Four patients progressed during the treatment: 1 RA to RAEB, 1 RAEB to RAEBt and 2 RAEB, both with very complex chromosomal abnormalities at the beginning of the therapy, to acute erythroleukemia (AML-M6). Pretreatment delta-aminolevulinic acid synthase and heme synthase activities were generally low. Five patients had mild thrombophlebitis, but not after the infusion procedure was changed. No other side-effects common to growth factors occurred. In conclusion, it is likely that heme arginate has a therapeutic effect on some MDS patients, obviously by stimulating erythropoiesis. The response may be long-lasting.

Adult↗
PubMed1990

Participation of CD11a-c/CD18 and RGD-recognizing adhesion molecules in the binding of LGL to fibroblasts. Evidence for the role of CD11a in the fibroblast-mediated inactivation of NK cells.

We have previously shown that large granular lymphocytes (LGL) are inactivated by contact with natural killer (NK) resistant monolayer target cells. In this work we have analysed which adhesion molecules are involved in the binding of LGL to such targets, as exemplified by fibroblasts, and in the subsequent inhibition of their NK activity. The results indicate that antibodies against CD54 (intercellular adhesion molecule 1, ICAM-1), CD11a (leucocyte function antigen 1, LFA-1, alpha chain), and CD18 (common beta chain of the beta 2-integrin family) significantly (by 50%) reduce the binding of LGL onto inhibitory target cells. The matrix protein-based synthetic peptide RGD and anti-CD29 (the common beta chain of the beta 2-integrin family) antibodies also diminish the binding (by 35%). The effects of the antiadhesion molecule antibodies and the peptide are additive, the combination of both leading to an almost complete block of adhesion. It may be hypothesized that some of the binding-relevant adhesion molecules of the RGD-binding domain on LGL (CD29) may be involved in the delivery of the inactivating signal to the effector cell. Indeed, incubation of LGL with anti-CD11a antibodies, but neither with antibodies against other binding-relevant epitopes nor with RGD, significantly reduced their NK activity. The mechanism of the inactivation was similar to that induced by intact NK-resistant target cells. On the basis of the present results we suggest that the CD11a molecule is involved in the down-regulation of the NK activity of peripheral blood lymphocytes.

Antibodies, Monoclonal↗
PubMed1987

Induction of large granular lymphocyte morphology in human peripheral blood mononuclear cells.

The transformation of human agranular blood lymphocytes into large granular lymphocytes (LGL) was studied. On the average, 2.8% of peripheral blood lymphocytes differentiate in less than 24 hr into LGL when cultured with autologous plastic-adherent monocytes and the Burkitt's lymphoma cell line Raji. The LGL precursors were intermediate-density lymphoid cells that were heterogenous for T3, T8, and Leu-7 antigens, negative for T4 and Leu-11, and positive for NK-9. During the transformation, frequency of Leu-11-positive cells increased and the cytotoxic activity was augmented. In single cell cytotoxicity experiments, the number of binding cells increased, whereas the number of killer cells among the binding cells remained unaltered. The transformation inducing factor was detectable in coculture supernatants of Raji and monocytes or Raji and the myeloid cell line ML-2. Analyses of the Raji-ML-2 coculture supernatants with reverse phase and gel filtration high-pressure liquid chromatography indicated that the factor is a heat- and trypsin-sensitive hydrophilic molecule with an apparent m.w. of 1000.

Antibodies, Monoclonal↗
PubMed1985

C-reactive protein for detection and follow-up of bacterial and fungal infections in severely neutropenic patients with acute leukaemia.

To evaluate the aetiology of febrile episodes and to rationalize our politics with antibiotics, C-reactive protein (CRP) was determined immunoturbidimetrically in 20 consecutive neutropenic adults with acute leukemia. They had 35 febrile episodes, 89% of which were infectious. Twenty per cent of infections were fungal. A similar CRP response was seen both in bacterial and in fungal infections. In 84% of infections the peak value for CRP rose greater than 100 mg/l. Thirty-five apyrexial patients with acute leukaemic and 20 healthy adults served as controls. Their CRP was less than 10 mg/l in 87%. CRP proved most valuable in the follow-up of infections, in the detection of infectious complications and in the detection of possible invasive fungal infections. Although relapse itself did not effect on CRP levels, extramedullary bone infiltration in two of our patients resulted in increased CRP production, which normalized with cytostatics only.

Acute Disease↗
PubMed1984

Inhibition of activity of human NK and K cells by simple sugars: discrimination between binding and postbinding events.

A variety of sugars were tested for their ability to inhibit the lytic activity of highly purified populations of human natural killer (NK) cells (large granular lymphocytes [LGL] ). Studies were also performed to determine whether inhibitory sugars were active at the level of recognition and binding to target cells (as determined by conjugate formation) or at a postbinding lytic stage. Mannose-6-PO4 and galactose-6-PO4 demonstrated strong and consistent inhibition of NK cytolysis at 50 mM concentration, while nonphosphorylated analogs were at most minimally effective. The inhibitory phosphorylated sugars did not block conjugate formation, indicating that the sugars affected some postbinding event rather than recognition of target cells by NK cells. The inhibition of NK activity by some sugars was not paralleled by inhibition of antibody-dependent cellular cytotoxicity (ADCC) activity by LGL. This suggests some divergence in the lytic mechanisms for NK and ADCC.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1982

Natural killer cell activity in the rat. Analysis of effector cell morphology and effects of interferon on natural killer cell function in the athymic (nude) rat.

Athymic (nude) rats were found to have increased levels of natural killer (NK) activity, 3- to 5-fold higher than in euthymic rats. Studies were performed to determine the nature of the NK cells in these animals and the basis for their increased cytotoxic reactivity. Large granular lymphocytes (LGL), which were previously shown to be the NK cells in euthymic rats, were increased 2- to 7-fold in the peripheral blood and spleen of nude rats. The LGL, enriched by centrifugation on discontinuous Percoll density gradients, were shown to have augmented NK activity similar to that seen with LGL-enriched fractions from euthymic rats. These results indicate that the NK cells in euthymic and athymic rats are morphologically and functionally similar, and that the higher NK activity in nude rats appears to be mainly attributable to an increased proportion of effector cells. In a single-cell cytotoxicity assay, interferon pretreatment of LGL was shown to increase: (a) the percentage of LGL which form conjugates with target cells; (b) the percentage of conjugate-forming cells which kill; and (c) the kinetics of lysis. Different effects were seen depending on the target cell tested.

Animals↗
PubMed1979

Decrease of the major high molecular weight surface glycoprotein of human granulocytes in monosomy-7 associated with defective chemotaxis.

By use of the galactose/NaB3H4 surface labeling technique followed by polyacrylamide slab gel electrophoresis, it is shown that the major labeled surface glycoprotein (GP130) of normal human blood granulocytes is markedly reduced in granulocytes from three patients with a chromosomal abnormality in all or most bone marrow mitoses. The abnormality consisted of monosomy-7 in two and deletion of the distal half of the long arm of chromosome-7 in the third. The granulocytes from these patients showed reduced chemotaxis. These results suggest that the expression of GP130, as well as the chemotactic ability of the cells, are at least in part controlled by one or several genes on chromosome-7. The GP130 protein may be involved in normal granulocyte chemotaxis.

Aneuploidy↗
PubMed1978

Contact with hospital, drugs, and chemicals as aetiological factors in leukaemia.

45 adults with acute leukaemia or chronic myeloid leukaemia and a control group of patients from the same hospital were asked about the people they had close social contact with before their illness, and about their use of drugs and chemicals. 18 (40%) leukaemia and 6 (13%) control patients had close social contact with hospital personnel or leukaemia patients. 8 (18%) leukaemia patients, but no control patients, had been in close contact with haemotological ward personnel. These differences were statistically significant. 9 (20%) leukaemia and 4 (9%) control patients lived in the same house as healthy persons working in a hospital. No conclusion could be drawn from differences between the two groups in their use of drugs, since the possibility that they were used to treat initial symptoms of leukaemia could not be excluded. Exposure to chemicals, including weed-killers and agricultural insecticides containing a benzene-ring known to be leukaemogenic, was about the same in the two groups.

Adolescent↗