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At least 757 records · Page 42Linked to original sources
PubMed1978

Immuno-suppressive effect of human macrophages. I. Evidence for an unstable soluble factor(s) inhibiting DNA synthesis and proliferation in PHA-stimulated lymphocytes.

Macrophages obtained by culturing blood monocytes in vitro for 8 days showed capacity to inhibit DNA synthesis and cell proliferation in PHA-stimulated lymphocytes separated from the macrophages by a membrane with pore size 0.2 micron. The DNA synthesis was measured as 3H thymidine incorporation and the proliferation as cell counts. The depression was reduced when the distance between macrophages and lymphocytes was increased concomitant with increased culture volume. Heat-killing of macrophages abolished their lymphocyte depressing capacity. Full inhibitory effect was established within 4 hours when lymphocytes were cultured in the proximity of macrophages. The effect was blocked by molecular filtration membranes with nominal molecular weight limits (nmwl) 1,000 and 10,000 whereas membranes with nmwl 25,000 only partially blocked the effect. No inhibitory effect was registered in the supernatants from macrophage-depressed lymphocyte cultures. Presumably the lymphocyte depressing effect is mediated via an unstable soluble factor(s).

Adult↗
PubMed1982

Alterations in the phenotype of hairy cells during culture in the presence of PHA: requirement for T cells.

Culture studies of peripheral blood mononuclear cells from 7 entirely typical cases of hairy cell leukemia showed that after culture in the presence of PHA for 2--5 days, the predominant cell type changed from E- SIg+ CIg+ gamma FcR+ muFcR+ hairy cells to an E+ SIg- CIg- gamma FcR-muFcR- population of transformed cells derived from hairy cells. Depletion and readdition experiments demonstrated that cell-to-cell contact with T cells was necessary for the phenotypic change, while several observations indicated that the E+ population was not derived from T cells present before culture. The E positivity of the cultured cells was shown to be due to the possession of E receptor not acquired from the culture fluid, but the cells differed from true T cells in lacking both mature and immature T-cell antigens. The relevance of these in vitro observations to the continuing controversy concerning the nature of the hairy cell and to the in vivo fluctuations in immunologic phenotype not infrequently observed in hairy cell leukemia is briefly discussed.

Antibodies, Monoclonal↗
PubMed1982

[Proliferation kinetics of PHA-stimulated lymphocytes after whole-body irradiation of patients with non-Hodgkin lymphomas (author's transl)].

A number of patients suffering from non-Hodgkin lymphomas received a whole-body irradiation with 15 rad per fraction (10 fractions). Before and after every second fraction, the proliferation kinetics of the peripheral lymphocytes was examined after PHA stimulation (DNA content per culture as cell number equivalent, incorporation of thymidine into DNA after isolation of DNA, distribution of cells within the cell cycle). After a total dose of 60 rad, the lymphocytes of nine among twenty patients showed a decrease of all proliferation-kinetic parameters. This decrease was followed by an increase up to values lying partly above the initial values. A second group did not show this increase. No correlations could be found between these changes and the clinical course or the symptomatology. The formation of micronuclei in lymphocytes of six patients could be examined before the whole-body irradiation and after an in-vitro irradiation. The results suggest the possibility of an individual determination of the radiosensibility of non-Hodgkin lymphomas.

Adult↗
PubMed1982

PHA induced blastoid transformation of lymphocytes in leprosy contacts.

PHA-induced blastoid transformation of lymphocytes was studied in 29 contacts of leprosy patients. 21 contacts taking DDS as prophylaxis showed significant depression of lymphocyte transformation while 8 contacts not taking DDS showed no depression as compared to controls. DDS thus has an inhibitory effect on cell mediated immune response.

Dapsone↗
PubMed1980

Immunologic studies of aging. V. Impaired proliferation of PHA responsive human lymphocytes in culture.

The impaired response to mitogens of lymphocytes from old persons has been shown to result from the presence of fewer responsive cells and the failure of these cells to divide normally after stimulation. We present additional evidence that the successive divisions of mitogen-responsive lymphocytes from old people are impaired. We labeled sister chromatids with BrdU and identified cells that were dividing for the first, second, or third time in culture. This analysis showed that lymphocyte cultures from old people contained only one-half the number of lymphocytes dividing for a second time and less than one-quarter the number of cells dividing for a third time compared with lymphocyte cultures from young people. It was shown that these changes reflected an absolute decrease in the number of second and third generation cells in cultures from old persons. No alterations in the cytokinetics of proliferation by lymphocytes from old people were found. These results provide additional evidence that mitogen-responsive lymphocytes from healthy elderly people do not undergo as many divisions in cultures with PHA as do lymphocytes from young persons.

Aging↗
PubMed1980

The influence of uremic sera on the blastic transformation of lymphocytes of healthy subjects, stimulated with non-specific mitogens (PHA, con A, PWM).

The influence of uremic sera on the blastic response of lymphocyte of healthy subjects to nonspecific mitogens (PHA, Con A, PWM) in 3-day culture was investigated. Sera were obtained from 19 patients with renal insufficiency, among them 3 groups were distinguished: terminal renal insufficiency and acute renal insufficiency, both treated by hemodialysis, and severe chronic renal insufficiency treated conservatively. Generally, the statistically significant inhibitory influence of uremic sera on the blastic transformation values of lymphocytes of healthy subjects stimulated with nonspecific mitogens was found. There were no significant changes in inhibitory activity of sera obtained before and after hemodialysis. Inhibitory properties of uremic sera were similar in regard to blastic transformations stimulated with all mitogens used. The studies on the influence of the experimental stationary dialysis in vitro on the inhibition of blastic transformation by the uremic sera showed that under the specific conditions of diffusion, blastic transformation inhibitors passed through dialysis membrane and were removed from the sera. Among all tested sera there were only 2 which did not lower the blastic transformation values. The fact that they were obtained from the chronically dialyzed patients with the longest period of dialysotherapy supported the above observation.

Adolescent↗
PubMed1980

Response of lymphocytes to nonspecific mitogens (PHA, Con A, PWM) in patients with glomerulonephritis.

Tests on blastic transformation of peripheral blood lymphocytes after stimulation with nonspecific mitogens (PHA, Con A, PWM) were performed on 55 patients suffering from glomerulonephritis and 32 persons belonging to the control group. On the basis of results obtained, the patients with glomerulonephritis were divided into three groups. The first, comprised patients with acute proliferative glomerulonephritis in whom the values of blastic transformation after stimulation by three mitogens used did not differ from the control group. The second, comprised patients with chronic proliferative, membraneous-proliferative, and membraneous glomerulonephritis. In 1/3 of them, a decrease blastic response to one of three mitogens was observed which was most often connected with stimulation by Con A. The third group comprised patients in the active phase of submicroscopic glomerulonephritis and lupus nephritis showing the lowest values of blastic transformation. The estimation of mitogen-induced blastic transformation was repeated in 17 patients after several weeks of nonsteroid anti-inflammatory drug therapy. After the treatment, values of spontaneous blastic transformation decreased statistically significantly. The mean values of mitogen-stimulated blastic transformation were also lower after the treatment, but the difference was not statistically significant.

Acute Disease↗
PubMed1980

PHA-induced, antibody-mediated and spontaneous cellular cytotoxicity toward chicken red blood cells in solid carcinomas and glioblastomas.

In 29 bronchogenic, 22 esophageal carcinomas and 17 glioblastoma peripheral mononuclear cells cytotoxicity toward chicken red blood cells was studied under three different sets of conditions: spontaneously induced, PHA induced, or mediated by antibodies toward target cells lysis. Cultures were 48 hours. While the cytotoxicity induced by mitogen and that medicated by antibody are diminished when compared to the control groups, spontaneous cytotoxicity shows values significantly higher in all the tumoral forms examined. Kinetically this type of lysis shows an already increased release of isotope after 24 hours and a steady rise in the successive hours. After depletion of adherent cells the mononuclear elements lose most of their lytic power. This datum, which contrasts with the diminished spontaneous cytotoxicity toward tumoral cells frequently described in the course of neoplasm, underlines the heterogenicity of the element responsible for SCMC and the diverse effects that the disease provokes on cell function.

Animals↗
PubMed1995

[The G1-process in human lymphocytes cultured with PHA, and formation of radiation-induced chromosome aberrations].

Experimental evidence for the existence of local spontaneous DNA synthesis in PHA-stimulated human lymphocytes at the G1 phase (G1 process) is presented. This process is associated with the appearance of single-stranded DNA breaks and their subsequent reparation. DNA sequences involved in the G1 process were characterized in terms of their nucleotide composition and association with the nuclear matrix. It was shown that the G1 process occurs in chromosome regions in which radiation-induced exchange-type chromosome aberrations arise. The results of the study are regarded as evidence in favor of a molecular version of the primary contact theory of chromosomal mutagenesis. A possible role of G1 process disturbances in pathogenesis of chromosome instability syndromes in humans is discussed.

Base Composition↗
PubMed1975

Production of leucocyte inhibitory factor (LIF) and macrophage inhibitory factor (MIF) by PHA-stimulated lymphocytes.

Supernatants from human mononuclear cells cultured with PHA inhibited the migration of both human polymorphonuclear leucocytes and guinea-pig peritoneal exudate cells, but not human mononuclear cells. Using ultrafiltration it was shown that these supernatants contained two inhibiting factors, the one with a molecular weight of 15,000-50,000 inhibited only guinea-pig peritoneal exudate cells (MIF), whereas the fraction containing molecules of a size between 50,000 and 75,000 specifically inhibited the migration of polymorphonuclear leucocytes (LIF). The polymorphonuclear leucocyte inhibiting activity was heat labile. It is suggested that the leucocyte migration inhibition test is dependent upon the production of a lymphokine (LIF) which acts specifically on polymorphonuclear leucocytes causing their inhibition of migration.

Animals↗
PubMed1978

The cytolytic effect of PUVA treatment on PHA-stimulated human peripheral lymphocytes.

The morphology of PUVA-treated and PHA-stimulated human peripheral lymphocytes in vitro was studied by means of the light and electron microscopes. Most cells showed signs of cytolysis, such as pyknotic nuclei and a swollen and decomposed cytoplasm; a few cells, however, appeared as normal lymphoblasts. In the latter, repair-enzyme mechanisms may successfully have rectified alterations in the DNS prior to the inception of S-phase. These findings are discussed with reference to the in vivo effect of PUVA treatment.

Cell Nucleus↗
PubMed1994

Some remarks on adherence reactivity of autologous PHA--transformed lymphocytes on human glial tumor cells in vitro.

In 16 patients with primary supratentorial and in 1 with cerebellar tumor among them 5 multiforme glioblastomas, 3 malignant astrocytomas, 6 astrocytomas of other subtypes and 1 mixed glioma (oligo-astrocytoma) the peripheral blood was drawn and lymphocytes were separated from it. Out of the removed part of the tumors about 10 cultures in each case were prepared and cultivated at least 14 days. When the growth zone was well developed the cultures were used for further studies. All samples of the separated lymphocytes activated with PHA were cultivated for 72 h. So prepared lymphocytes were added to the tumor culture in vitro and observed for 24 h. After that time the not adhered lymphocytes were removed and the remaining tissue cultures with adhered lymphocytes were fixed and stained and the number of lymphocytes was counted. It was found that 1 h after the addition of lymphocytes the number of lymphocytes was very high, though a great part of them did not adhere to the tumor tissue. After 24 h the number of adhered lymphocytes was small or minute. Taking into consideration the results obtained it seems that the low efficiency of therapy of gliomas with autologous lymphocytes in vivo can result from the very weak direct contact with tumor cells. The influence of lymphocytes can be very limited so more as the tumor cells can secret biological active substances like PGE2, which counteract the cytotoxic activity of lymphocytes. For that reason the number of lymphocytes can be of significant value as counterbalance to that properties of the tumor cells. Taking into account even secretion of tumor cells of the same biological active substances such as PGE2 which counteract the cytotoxic activity of lymphocytes for the efficient activity of lymphocytes the number of them may be of significant value.

Adult↗
PubMedDate not supplied

[The effect of streptococcal group A polysaccharide on PHA-induced T-cell proliferation].

The influence of group A streptococcal polysaccharide (A-PS) on the proliferation and functional activity of subpopulations CD4+ and CD8+ of human peripheral blood lymphocytes has been studied. As revealed in this study, A-PS, though having no mitogenic activity of its own, is capable of influencing the process of proliferation of two main T-cell subpopulations in the presence of PHA. Its action has a regulatory character and is manifested by the maintenance of the ration of lymphocytes CD4+ and CD8+ in the culture at a constant level (approximating 1). This effect is seemingly linked with changes in the functional activity of lymphocytes in both subpopulation CD4+ and subpopulation CD8+. The detected properties of A-PS make it possible to regard it as a pathogenic factor playing an important role in immunoregulatory disturbances in diseases connected with infection caused by group A streptococcus.

Adult↗
PubMed1996

Monoclonal antibodies against P-glycoprotein, an MDR1 gene product, inhibit interleukin-2 release from PHA-activated lymphocytes.

P-glycoprotein (Pgp), a product of the human MDR1 gene, is a member of the ABC superfamily of transporters responsible for the trafficking of biologically active substances across the membrane. In tumors, Pgp is associated with multidrug resistance (MDR), the phenomenon characterized by the ability of cells to efflux structurally diverse lipophilic compounds. It has been demonstrated that Pgp is also expressed on various types of normal human tissues and cells, including hematopoietic stem cells, T, B, and natural killer (NK) cells. The normal physiologic function of Pgp in immune cells is unclear. In this study, we used highly specific and nontoxic monoclonal antibodies (mAbs) against external epitopes of Pgp (mAb UIC2, its monovalent Fab fragments, and mAb MRK16) to inhibit Pgp-mediated efflux and investigate a possible role of Pgp in activated T lymphocytes. We found that the treatment of phytohemagglutinin (PHA)-stimulated peripheral blood leukocytes (PBL) with these mAbs resulted in a significant reduction of interleukin-2 (IL-2) levels in the culture. Early activation events, as measured by intracellular calcium flux, expression of the CD69 early activation marker, and expression of IL-2 mRNA, were not affected by anti-Pgp mAbs. These results suggest that the Pgp efflux pump may be involved in the transport of IL-2 in T lymphocytes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1977

The action of cysteine of PHA-stimulation of lymphocytes. II. Influence on incorporation of 3H-uridine and 14C-leucine.

The influence of short-term preincubation and continuous cultivation with L-cysteine hydrochloride on incorporation of 14C-leucine nad 3H-uridine in cultures of PHA-stimulated and unstimulated lymphocytes was studied. Preincubation during 1 and 2 hours in presence of cysteine inhibited incorporation of these compounds during the first few days of incubation. After 2-hr preincubation, incorporation was first somewhat depressed and then markedly enhanced. Continual presence of cysteine in the medium markedly inhibited incorporation of 3H-uridine and 14C-leucine from the first to last day of incubation.

Animals↗
PubMed1997

Multi-segmental innervation of single pontine reticulospinal axons in the cervico-thoracic region of the cat: anterograde PHA-L tracing study.

To characterize the fine morphology of individual reticulospinal axons at multiple spinal segments, localized injections of the anterograde neural tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), were made into the nucleus reticularis pontis oralis (NRPo) of the cat. Following survival periods of 6-8 weeks, labelled axons, between 1 and 8 microns in diameter, were found throughout the cervical and upper thoracic segments. Thick axons (diameter > or = 3 microns) were found to descend beyond the upper thoracic spinal cord, while most thin axons (diameter < 3 microns) ended in the upper cervical cord. From serial transverse sections (50 microns) of segments C3 to T2, in four cats, the trajectories of 23 single, thick reticulospinal axons were traced in continuity over distances of between 21.8 and 59.4 mm, corresponding to 3 and 8 segments, respectively. Most axons gave off at least one, and as many as four collaterals per segment, some preferentially in the cervical enlargement. The remainder gave off collaterals at most but not all segments. Detailed reconstruction of the collateralization and arborization in the spinal gray matter showed two major termination types, one where terminals remained ipsilateral to the stem axon, the other where additional collaterals extended across the midline from the ipsilateral gray matter to terminate in the contralateral gray matter. Axons tended to have collaterals of one type or the other, irrespective of the rostrocaudal level. Both ipsilateral and bilateral projections terminated mainly in laminae VII or VIII although the branching patterns varied from axon to axon. Individual stem axons, in general, showed similar termination patterns at each level.

Animals↗
PubMedDate not supplied

[Chromatin activation at early stages of PHA-stimulation of lymphocytes (cytofluorometric study)].

The activation of lymphocyte DNP-complex in peripheral blood of people 19-34 and 90 years was studied using the method of cytofluorometry. After stimulation with PHA, a trustworthy increase in fluorescence within a range of 530 nm was observed after 15 and 60 minutes. No significant differences were revealed in activation of the DNP -complex in the people aged 19-34 and 90.

Adult↗
PubMed1997

CD3-/HLA-DR+, CD3+/HLA-DR+ cell levels and PHA stimulation of lymphocytes obtained from women with recurrent spontaneous abortions and subjected to partner's lymphocyte immunization.

It is assumed that 80% of recurrent spontaneous abortions (RSA) of unknown etiology are of immunological origin. The proposed experimental treatment of those patients could be immunization with paternal lymphocytes, though the exact mechanism through which this therapy exerts its effect is still unknown. Some authors suggest that lymphocyte alloimmunization alters the number and activity of particular subpopulations of peripheral blood lymphocytes. The aim of this study was to evaluate the proliferative O activity of lymphocytes stimulated with phytohemagglutinin (PHA) and the percentage of peripheral lymphocytes carrying CD3+/HLA-DR+ and CD3-/HLA-DR+ markers, present in 32 selected for this study RSA women subjected to paternal lymphocytes' alloimmunization performed prior to conception and in early pregnancy. We conclude that, the post-immunization changes seem to have different quantitative and qualitative character comparing to those seen in normal pregnancy. They seem to avert unfavourable immunological phenomena observed in RSA women, allowing for successful continuation of pregnancy.

Abortion, Habitual↗