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Biomedical subjects

T Diamantstein

Publications and source records attributed to T Diamantstein.

At least 217 records · Page 12Linked to original sources
PubMed1979

Studies on the relevance of microtubules and of microfilament-dependent processes for triggering lymphocyte activation.

The effects of Isoptin i) on isolated microtubules, ii) on the anti-immunoglobulin and the Concanavalin A induced changes in the plasma membrane topography of murine lymphocytes and iii) on murine lymphocyte activation by lipopolysaccharide and by Concanavalin A was investigated. Isoptin and lidocaine (a local anaestetic) inhibited repolymerisation of tubulin into microtubules and induced depolymerisation of microtubules. Isoptin and lidocaine inhibited competitively binding of colchicine (a classical microtubules disrupting agent) to tubulin. Isoptin induced changes in the plasma membrane topography resembling effects caused by local anaesthetics or by a combination of colchicine and cytochalasin B (an agent affecting microfilament function). Isoptin, lidocaine, colchicine and hydroxyurea when present in the culture medium during the whole incubation period inhibited DNA synthesis induced by lipopolysaccharide or Concanavalin A. RNA synthesis was completely inhibited by lidocaine but not by Isoptin or by colchicine. If Isoptin, colchicine or hydroxyurea were removed from the culture medium at 20 h of culture period, the cells immediately started to incorporate 3H-Thymidine. The inhibitory action of lidocaine was irreversible. These results show that Isoptin, a drug which depolymerizes microtubules in vitro and disturbs the mitogen induced changes in plasma membrane topography of lymphocytes (believed to be controlled by microtubules and microfilaments), does not abolish commitment of the cells for DNA synthesis.

Animals↗
PubMed1978

Studies on induction and control of cell-mediated autoimmunity. I. Induction of "autoreactive" T lymphocytes in mice by cyclophosphamide.

Injection of a single dose of cyclophosphamide (CY) (125 mg/kg) or a combination of a small dose of CY (20 mg/kg) and 2.5 mg/kg lipopolysaccharide induces a transient appearance of autoreactive T lymphocytes (T-ARC) in the spleens of mice. The T-ARC activity reaches a peak 6 days after CY injection and could not be detected 8 days after this treatment. For testing T-ARC activity, spleen cells were injected into the footpads of syngeneic recipients, and the resulting lymph node enlargement at the draining site of cell inoculation and the content of nucleated cells in the lymph node was determined. Possible explanations of this autoimmune phenomenon are discussed. It is postulated that CY-resistant precursors of T-ARC are stimulated by "new" antigenic sites present on the surface of B lymphoblasts repopulating the CY-damaged spleen in a period of transient absence of CY-sensitive suppressor cells.

Animals↗
PubMed1978

Studies on induction and control of cell-mediated autoimmunity. II. Prevention of induction and activity of autoreactive T cells by suppressor cells and by a suppressive serum factor.

Autoreactive T lymphocytes (T-ARC) can be detected in the spleen of mice treated with a single dose of cyclophosphamide (CY) (125 mg/kg), a peak occurring 6 days after CY injection. Eight days after CY treatment, the mice develop a specific anergic state. This anergic state can be transferred to normal syngeneic animals by either splenic nylon wool-nonadherent lymphocytes (suppressor cells, S-ARC) or by the serum of anergic mice, implying the development of an active suppressive mechanism due to CY treatment. Precursors of both potentially T-ARC as well as S-ARC coexist in the spleen of normal animals. Precursors of S-ARC present in the spleen and in the thymus of normal animals are sensitive to CY. However, committed S-ARC obtained from anergic mice are resistant to CY. Committed S-ARC as well as their precursors prevent induction of T-ARC. Committed S-ARC counteract expression of committed T-ARC activity, whereas precursors of S-ARC fail to do so. The autoimmune phenomenon described here represents an in vivo animal model system for induction of T-ARC and for the control mechanism which normally prevents induction and/or expression of cell-mediated autoreactivity by specific suppressor cells and by suppressive factors.

Animals↗
PubMed1978

Specific binding of poly(I)-poly(C) to the membrane of murine B lymphocyte subsets.

Indirect immunofluorescence revealed that 13% of BALB/c and 33% of CBA spleen cells of B type carry specific binding sites at their surface for double-stranded poly(I).poly(C). Pretreatment of BALB/c spleen cells with anti-mouse immunoglobulin serum increased the number of B cells capable of binding poly(I).poly(C) indicating the existence of a second B lymphocyte subpopulation carrying masked poly(I).poly(C)-binding sites. Pretreatment of the cells with mitogenic doses of either lipopolysaccharide (LPS) or single-stranded polynucleotides, e.g. poly(I) or double-stranded poly(A).poly(U), failed to affect binding of poly(I).poly(C) to the cells. Poly(I).poly(C) converts small poly(I).poly(C)-binding lymphocytes into lymphoblasts carrying poly(I).poly(C)-binding sites. Lymphoblasts derived from LPS-stimulated cells do not carry poly(I).poly(C)-binding sites. Thymocytes or splenic T cells failed to bind poly(I).poly(C). As measured by thymidine uptake, CBA mice containing a higher percentage of poly(I).poly(C)-binding cells, are high responder mice to poly(I).poly(C), compared with low responder BALB/c mice.

Animals↗
PubMed1978

Inhibition by isoptin (a calcium antagonist) of the mitogenic stimulation of lymphocytes prior to the S-phase.

Isoptin (alpha-isopropyl-alpha-(N-methyl-N-homoveratryl)-gamma-amino-propyl-3,4-dimethoxyphenylacetonitril-hydrochloride)--a calcium antagonist--inhibits mitogenic stimulation of lymphocytes. Isoptin acts prior to the S-phase of the cehl cycle but does not prevent the early events involved in triggering of cell mitosis. The drug seems to be a good tool for studying the relevance of the 'early events' assumed to be involved in lymphocyte stimulation.

Animals↗
PubMed1977

Localization of proliferating cells in lymphatic tissues triggered by dextran sulfate.

Mice were injected with dextran sulfate in the presence or absence of various amounts of sheep red blood cells. The incorporation of thymidine into the proliferating cells of spleen, lymph nodes and thymus was investigated using autoradiographic and histologic techniques. Dextran sulfate triggered selective proliferation of cells localized in the marginal zone of the white pulp of the spleen. The uptake of colloid carbon particles was also enhanced by dextran sulfate in this area of the spleen. The results are consistent with the suggestion that dextran sulfate triggers proliferation of non-thymus-derived cells probably a sub-population of B-lymphocytes and activates phagocytic cells.

Animals↗
PubMed1976

Differences between lymphoid cell populations of guinea pigs and mice as determined by the response to mitogens in vitro.

The stimulation of guinea pig lymphocytes by phytohemagglutinin (PHA), concanavalin A (ConA), methanol-extracted residues of tubercle bacilli (MER), purified protein derivative of tubercle bacilli (PPD), dextran sulphate (DS) and E. coli lipopolysaccharide (LPS), was determined and compared with that of mouse lymphoid cells. The sources of lymphocytes tested were spleen, thymus, lymph nodes and bone marrow. The degree of activation of DNA synthesis by PHA and ConA was higher in guinea pig thymocytes and lymph node cells than in corresponding sources of mouse lymphocytes. The optimum degree of stimulation by PHA and ConA was approximately the same in guinea pig thymocytes, while ConA was by far a better stimulator than PHA for mouse thymocytes. All four B-cell mitogens tested (MER, DS, PPD and LPS) activated DNA synthesis in mouse lymphoid cells while only MER and DS were effective in guinea pig lymphocytes. A guinea pig spleen cell population depleted from B cells was not stimulated, neither by DS nor by MER, while it still responded to PHA and ConA. These results indicate that the proliferative response due to MER and DS occurs in the B-cell compartment. It is suggested that the differences between guinea pigs and mice with respect to their ability to develop a cell-mediated type immunity and to respond to T-independent antigens are related to differences in the relative proportions and degrees of maturation of T- and B-cell subpopulations, as reflected by the selective responsiveness to various mitogens.

Animals↗
PubMed1976

Changes in thymocyte reactivity to lectins induced by B-cell mitogens of the type of sulphated polyanions.

Dextran sulphate, polyvinyl sulphate and carrageenan (but not the other polyanions tested, such as poly I:poly C, poly-L-glutamic acid or E. coli lipopolysaccharide) act synergisticaly with PHA on mouse thymocyte stimulation, as measured by thymidine uptake and blast cell transformation. Furthermore the active compounds shift the dose response of thymocytes to Con A. The effect could be observed in four different strains of mice tested by using normal or cortisone-resistant thymocytes. Two possibilities are envisaged for explanation of these effects: (a) attachment of polyanions by their anionic groups to cell surface constituents and interaction of the sulphate groups of the polymers with plant lectins; and (b) modification of the cell membrane induced by sulphated polymers changing either the binding capacity or the effectiveness of the membrane-associated events leading to thymocyte stimulation by the lectins.

Animals↗
PubMed1976

Two distinct lumphocyte-stimulating soluble factors (LAF) released from murine peritoneal cells. I. The cellular source and the effect of cGMP on their release.

Culture fluids of murine peritoneal cells contain two distinct, non-dialysable priniciples (LAF) with thymocyte proliferation-stimulating properties. One of them is elaborated from phagocytic cells (presumably macrophages), the other is released by non-phagocytic cells (lymphocytes). cGMP added exogenously stimulates the production and/or release of LAF from phagocytic cells, but not from non-phagocytic cells. The phagocytic cells (but not the lymphocytes) require intact RNA and protein synthesis for LAF release. The action of LAF differs from those of cGMP itself by being non-dialysable, and unable to prevent the inhibitory action of cAMP on mitogen-stimulated lymphocyte proliferation.

Animals↗
PubMed1976

Suppression of the primary immune response in vivo to sheep red blood cells by B-cell mitogens.

Polyacrylic acid (PAAC), lipopolysaccharide (LPS), dextran sulphate (DS) and purified protein derivative of tubercle bacilli (PPD), compounds mitogenic for B lymphocytes in vitro, suppressed the immune response of mice to SRBC in vivo, when injected 4-2 days before immunization. The same compounds enhanced the immune response when injected half an hour before immunization of the animals with a suboptimal antigen dose. A subsequent injection of PAAC given shortly before immunization, abolished the immunosuppressive effect expected by pretreatment of the animals with either PAAC or LPS. A second injection of LPS abolished the immunosuppressive effect of LPS only. The results indicate that when B lymphocytes react with a mitogen in the absence of a particular antigen, they temporarily lose their capacity to respond to antigen.

Acrylates↗
PubMed1975

Effect of cyclic nucleotides on DNA synthesis in mouse lymphoid cells.

The effect of eight cyclic purine and cyclic pyrimidine nucleotides on DNA synthesis on mouse lymphoid cells was investigated. Two out of eight compounds tested, namely 2', 3'-cyclic guanosine monophosphate (2', 3'-cGMP) as well as 3', 5'-cyclic guanosine monophosphate (3', 5'-cGMP), stimulate thymidine incorporation in all types of lymphocytes tested. The stimulatory activity of the cyclic guanosine nucleotides as well as the effects of lectins could be antagonized by 3', 5'-cyclic adenosine monophosphate (3', 5'-cAMP). 2', 3'-cGMP seems to stimulate preferentially mature T-cells while 3', 5'-cGMP preferentially acts on B-cells.

Animals↗
PubMed1975

Mitogenic and adjuvant activity of a methanol extraction residue (MER) of tubercle bacilli on mouse lymphoid cells in vitro.

The mitogenic and adjuvant effect in vitro of MER (methanol extracted residue of tubercle bacilli), on Balb/C and nu/nu immunocompetent cells was examined and compared with the effect of PPD, LPS, DS, PHA and ConA. MER activated DNA synthesis in spleen cells of Balb/C and nu/nu mice and in blood cultures of Balb/C. The stimulation of DNA synthesis by MER in spleen cells was not macrophage dependent. Bone marrow and 1ymph node cells were slightly stimulated while thymus cells were not affected. Both MER and PPD enhanced the in vitro immune response of Balb/C mice to SRBC and to TNP (trinitrophenyl) hapten. MER, LPS and PPD enhanced the immune response of nude spleen cells to SRBC in vitro.

Adjuvants, Immunologic↗
PubMed1975

Relationship between biological activities of polymers. I. Immunogenicity, C3 activation, mitogenicity for B cells and adjuvant properties.

The effect of thirteen compounds on C3 activation, mitogenicity for B lymphocytes and on the immune response was tested. Only two of the compounds tested, polyinosinic acid and a high molecular weight polyethylenesulphate induced C3 conversion, while eleven out of the thirteen compounds (negative charged immunogenic or non-immunogenic polymers including the three C3 active compounds) stimulated thymidine incorporation in B lymphocytes. The non-charged (T-independent) immunogens dextran and polyvinylpyrrolidone neither activated C3 nor BP lymphocytes. With the exception of single-stranded polyribonucleic acids, the compounds stimulating DNA synthetis in B cells enhanced the response of the mice to a suboptimal dose of sheep red blood cells. In conclusion C3 activation, intrinsic (T-independent) immunogenicity and B-cell stimulation are not correlated properties. However, B-cell mitogenicity and adjuvanticity seem to be related.

Adjuvants, Immunologic↗
PubMed1975

The control of immune response in vitro by Ca2+. II. The Ca2+-dependent period during mitogenic stimulation.

The Ca2+ requirement for stimulation of DNA synthesis in vitro by phytohaemagglutinin (PHA) and by lipopolysaccharide (LPS) was investigated using mouse spleen cells. During mitogenic stimulation two periods could be distinguished: a Ca2+-independent period which was followed by a Ca2+-dependent period. The results suggest that Ca2+ is required for a step preceeding DNA synthesis but not for the early initial phase of transformation.

Animals↗