The effect of ascitic fluid globulins on the growth of leukemia P388/DOX and Ehrlich's carcinoma in mice]

The study was performed to investigate the effect of ascitic fluid globulins of tumor on tumor growth and life span of mice. The globulins are shown to shorten the life span of Ehrlich tumor mice from 86.8 to 61.8 days, to increase 3-5-fold the growth rate of Ehrlich carcinoma and P388/DOX tumor. It was found that globulins of ascitic fluids and serum globulins of tumor have equal effects of tumor growth. It is proposed to use globulins of ascitic fluid to study the globulin role in tumor growth.     

The intracellular pH of the peripheral blood lymphocytes in cattle during the development of leukemia]

The intracellular pH distribution of peripheral cattle lymphocytes has been studied in normal state and at six stages of the development of bovine leukosis by the dye microfluorimetry of single cells. It has been shown that the increase of mean intracellular pH value occurs as well some distribution parameters, such as pH range and asymmetry change during the disease process. Probable reasons responsible for the observed modification of the distribution pattern are discussed.     

The expression of P-glycoprotein in leukemia P388 cells with induced doxorubicin resistance]

beta-D-galactose-containing glycoproteins were prepared from cells P-388 leukemia and from P-388 leukemia cells with induced resistance to doxorubicin. It was shown by HPLC method that plasma membranes from resistant cells contain 4-4.5% P-glycoproteins and plasma membranes from sensitive cells contain P-glycoproteins about 10 times lower.     

Frequency of large granular lymphocytes in peripheral blood of healthy persons and breast cancer patients

Summary The frequency of large granular lymphocytes (LGL) in the peripheral blood of healthy persons (n=56) and breast cancer patients (31 cases with stage-I and -II disease and 42 cases with stage-III and -IV disease) was studied. The frequency of LGL in peripheral blood was significantly depressed in cancer patients, and particularly in patients with advanced breast cancer.     

Frequency of large granular lymphocytes in peripheral blood of healthy persons and breast cancer patients

The frequency of large granular lymphocytes (LGL) in the peripheral blood of healthy persons (n = 56) and breast cancer patients (31 cases with stage-I and -II disease and 42 cases with stage-III and -IV disease) was studied. The frequency of LGL in peripheral blood was significantly depressed in cancer patients, and particularly in patients with advanced breast cancer.     

Comparison of the effect of IL-2 and IL-6 on the lytic activity of purified human peripheral blood large granular lymphocytes

The effects of IL-6 and IL-2 on highly purified, human peripheral blood large granular lymphocytes (LGL) were investigated and compared. IL-6 enhanced LGL NK activity in a dose-dependent manner against K562, however IL-2 was a more potent stimulus of LGL NK function. Neither IL-2 nor IL-6 increased LGL cytotoxic potential in a parallel estimation of heteroconjugated antibody (anti-CD16 x anti-nitrophenyl mAb)-dependent cytotoxicity against nitrophenyl-modified YAC. Unlike IL-2, IL-6 did not significantly induce LGL lymphokine-activated killer activity, LGL proliferation, or LGL lymphokine production. In particular, IL-6 did not stimulate detectable LGL IL-2 production or IL-2R modulation, and mAb to the p75 IL-2R had no effect on IL-6 induction of LGL NK activity. Therefore, in the absence of T cells, IL-6 provided an IL-2-independent signal to LGL that resulted in augmentation of their NK activity without stimulating their proliferation or other LGL functions.     

Increase in peripheral large granular lymphocytes in postpartum autoimmune thyroiditis

In order to elucidate the mechanism of postpartum aggravation of autoimmune thyroid disease (AITD), we serially examined the change in the proportion of peripheral large granular lymphocytes (LGL), which have activities of NK, K and/or cytotoxic T cells, in their postpartum period. Within 6 months postpartum, the percentage of LGL increased transiently in patients with AITD who remained euthyroid, or developed destructive thyrotoxicosis and/or hypothyroidism due to thyroiditis and even in normal controls. These changes in the LGL percentage were more obvious in the patients who had marked postpartum thyroid dysfunction. In contrast, we did not find a definite increase in the LGL percentage within 6 months postpartum in patients with Graves' disease who relapsed into Graves' thyrotoxicosis. These deta suggest that the increase in LGL in the postpartum period may be related to the induction of postpartum destructive thyrotoxicosis and/or hypothyroidism in AITD.     

Fc gamma-receptor-bearing, non-B lymphocytes in human peripheral blood: cytophilic immunoglobulin binds almost exclusively to large granular lymphocytes

Cytophilic IgG (CYT-Ig) has previously been reported to bind to both the "TG" (E+, Fc gamma R+) and "L" (E-, Fc gamma R+) subsets of non-B lymphocytes in human peripheral blood. Present investigations show that IgG-binding cells, as detected by a sensitive antiglobulin rosetting reaction, are contained almost entirely within the large granular lymphocyte (LGL) subpopulation, and that fewer than 5% of other non-B lymphocytes acquire IgG from serum. Cell membrane-bound IgG sterically blocks the reaction of LGL with sheep red blood cells and therefore influences the proportions of these cells characterized as TG (E+) or L (E-) lymphocytes. Although the majority of TG lymphocytes are LGL, a further subpopulation of E+, Fc gamma R+ cells are detectable under particular test conditions. Unlike LGL, these lymphocytes do not react with rabbit IgG-coated ox RBC (EAG) in saline, but will form EAG rosettes when the reaction is enhanced in the presence of Ficoll. These Fc gamma R+ cells are mostly of typical small-lymphocyte morphology and do not bind detectable amounts of CYT-Ig, nor do they express the monoclonal antibody-defined VEP 13 determinant associated with Fc gamma R on LGL.     

Proliferation of human peripheral blood lymphocytes induced by recombinant human interleukin 2: contribution of large granular lymphocytes and T lymphocytes

Recombinant human interleukin 2 (rH IL-2) in the presence or absence of additional stimuli, was found to be able to induce and support the proliferation of human peripheral blood lymphocytes (PBLs). These proliferative effects were observed at low doses (less than or equal to 10 U/ml) of interleukin 2 (IL-2) only when additional signals (antigen, mitogen) were provided. However, higher doses (greater than or equal to 100 U/ml) of rH IL-2 significantly stimulated the proliferation of PBL even in the absence of exogenous lectin, antigen, or allogeneic serum. The subpopulation of lymphocytes most responsive to these higher doses of rH IL-2 was the large granular lymphocyte (LGL), the morphologic homologue of natural killer activity. After the separation of human PBLs on discontinuous Percoll gradients, cells from fraction 2 (greater than 90% LGLs) responded in a dose-dependent manner to rH IL-2 alone, whereas cells from fraction 6 (greater than 90% T cells) were only slightly responsive to rH IL-2 alone. A portion of the proliferation of cells from fraction 2 was dependent on the expression of the TAC receptor, because the prior removal of TAC-positive cells significantly reduced IL-2-induced lymphocyte proliferation. These results demonstrate that human LGL that have not been exogenously stimulated can proliferate in direct response to IL-2, and suggest that LGL are the major cellular phenotype in the proliferative response that has been observed clinically.     

The effect of finoptin on the accumulation of doxorubicin in leukemia P388 cells with induced resistance to the antibiotic

Using male mice BDF1, it has been shown that the retention period of doxorubicin (DOX) is shorter in the leukemia P 388 cells with induced antibiotic resistance (P 388/DOX) as compared to the P 388 cells, sensitive to DOX. Administration of finoptin (FP) to animals leads to the increase of DOX concentration in the leukemia P 388/DOX cells during 240 min observation. FP promotes the therapeutic effect of DOX on mice bearing leukemia P 388/DOX. It can be suggested that the mechanism of FP action is the damaged DOX elimination from cells with induced resistance, since FP doesn't change the period of antibiotic circulation in the murine blood plasma.     

Intracytoplasmic inclusions in the peripheral blood lymphocytes of patients with chronic lymphatic leukemia

An ultrastructural survey of peripheral blood lymphocytes in 81 patients with chronic lymphatic leukemia (CLL) demonstrated intracytoplasmic inclusions in 15 of them. These inclusions consisted of round, dense bodies, ferritin deposits, lipid-containing bodies, concentric rings of endoplasmic reticulum, microfibrillar formations and crystalloid inclusions. The variety of these inclusions suggests that cases diagnosed by light microscopy as classical CLL are actually subtypes which may differ in their clinical course and ultimate prognosis.     

The cytogenetic effect in peripheral blood lymphocytes as an indicator of the effect on man of factors of the Chernobyl accident]

The data obtained confirm the possibility of both individual and population cytogenetic indication of the effect of low intensity radiation, exceeding the background level, and exhibit a positive correlation with the radio-ecological situation formed. The cytogenetic effect, that indicates the disturbance of the genome stability, might be considered as an indicator of a high probability of occurrence of pathologies, with a genetic component, in the subpopulations under study, compared to spontaneous level.     

Infection of peripheral blood lymphocytes in sheep with bovine leukemia virus in vitro

Continuous cultivation of peripheral blood lymphocytes from healthy sheep was carried out in vitro with the help of human recombinant interleukin-2. Lymphocytes were concurrently cultivated with the lethally X-rayed BLV-producing FLK culture cells. Electron microscopy and dot-blot hybridization established that sheep peripheral blood lymphocytes were infected with BLV and a full cycle of replication takes place in them. Infection of sheep leukocytes in vitro can be used to study the mechanisms of leukogenesis in vitro.     

Biotransformation of mafosfamide in P388 mice leukemia cells: intracellular 31P-NMR studies

The intracellular transformation of cis-mafosfamide has been studied in P388 mice leukemia cells using 31P-NMR spectroscopy. For this purpose the cells were entrapped in low-gelling-temperature agarose threads. Internal pH of the cells, determined from the position of the intracellular inorganic phosphate, was 7.2. The cell membrane was permeable to 4-hydroxycyclophosphamide and aldophosphamide and less permeable to phosphoramide mustard. 4-Ketocyclophosphamide and carboxyphosphamide signals were not detectable in cells either sensitive or resistant to oxazaphosphorine treatment.     

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.