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Biomedical subjects

R Blumenthal

Publications and source records attributed to R Blumenthal.

At least 181 records · Page 10Linked to original sources
PubMed1977

Liposome--lymphocyte interaction: saturable sites for transfer and intracellular release of liposome contents.

The water-soluble dye 6-carboxyfluorescein was trapped in the internal aqueous compartments of small sonicated dioleoyl lecithin vesicles and used to assess the kinetics of transfer of vesicle contents to human lymphocytes. By using flow microfluorometry, the initial rate of dye transfer to the cells was measured as a function of the concentration of vesicles in the external medium. The rate of transfer consists of at least two components, one of which saturates at high vesicle concentration and the other of which does not saturate in the range of concentrations explored. The saturable component was competitively inhibited by vesicles not containing dye. Both the saturable and nonsaturable components of transfer were inhibited by fetal calf serum or bovine serum albumin but neither component was affected by bovine IgG, choline chloride, or heparin. Pretreatment of the lymphocytes with trypsin or Pronase had no effect on either component. The saturable component can be interpreted in terms of a two-step process in which vesicles bind reversely to sites on the cell surface, and dye is then transferred into the cell from the vesicle-site complex.

Blood↗
PubMed1977

Ionophorous activity and murine B lymphocyte mitogens.

The relationship between ionophorous and B cell mitogen activity has been investigated. Most known ionophores were nonmitogenic for mouse spleen cells. In addition, when tested in a bilayer lipid membrane (BLM) apparatus, most types of B cell mitogens were nonionophorous. However, excitability-inducing material (EIM), a high m.w. polymeric protein, which is a channel-forming ionophore, was a potent mitogen for mouse B lymphocytes. Similarly, keyhole limpet hemocyanin (KLH), a high m.w. polymeric protein, which is a B cell mitogen, is a channelforming ionophore. The mitogenic activities of these two compounds were not due to contamination with endotoxin since they produced weak or absent responses in the limulus lysate clotting and rabbit pyrogenicity assays, and were also mitogenic for spleen cells of endotoxin-low responder C3H/HeJ mice. Both the mitogenic and ionophorous activities of EIM and KLH were dependent on their polymeric structure since dissociation of these compounds into monomeric subunits markedly decreased both activities. However, heat denaturation destroyed their ionophorous ability but preserved their mitogenicity, thereby demonstrating that ionophorous activity was not essential for B cell activation. These data suggest that B cell mitogens do not necessarily act as primary ionophores. However, we propose that these molecules intercalate into the lipid portion of the cell membrane, and that this interaction initiates the process of B cell activation.

Animals↗
PubMed1975

Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells.

Horizontal lipid bilayer membranes were used as a model system to study lymphocyte-mediated killing of target cells. Dinitrophenylated lipid bilayers can physically support dozens of lymphocytes for periods of over one hour without breakage or increasing the electrical conductance of the membrane. However, in the presence of antibody against Dnp, human lymphocytes rapidly induced increases in membrane conductance of several orders of magnitude without membrane breakage. Such ionic permeability increases occurred only when the membrane voluage was positive on the lymphocyte side, as would be the case with a target cell membrane. The lymphocyte and antibody dependence of this conductance increase parallels that observed for lymphocyte killing of antibody-coated target cells. The results are interpreted as evidence that the primary event in lymphocyte killing of antibody-coated target cells is the creation of ion-conducting channels in the target membrane.

Animals↗
PubMed1974

Kinetics of the opening and closing of individual excitability-inducing material channels in a lipid bilayer.

The kinetics of the opening and closing of individual ion-conducting channels in lipid bilayers doped with small amounts of excitability-inducing material (EIM) are determined from discrete fluctuations in ionic current. The kinetics for the approach to steady-state conductance during voltage clamp are determined for lipid bilayers containing many EIM channels. The two sets of measurements are found to be consistent, verifying that the voltage-dependent conductance of the many-channel EIM system arises from the opening and closing of individual EIM channels. The opening and closing of the channels are Poisson processes. Transition rates for these processes vary exponentially with applied potential, implying that the energy difference between the open and closed states of an EIM channel is linearly proportional to the transmembrane electric field. A model incorporating the above properties of the EIM channels predicts the observed voltage dependence of ionic conductance and conductance relaxation time, which are also characteristic of natural electrically excitable membranes.

Cholesterol↗