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Biomedical subjects

E M Hadden

Publications and source records attributed to E M Hadden.

At least 37 records · Page 2Linked to original sources
PubMed1977

Phorbol myristate acetate: a mitogen selective for a T-lymphocyte subpopulation.

Phorbol myristate acetate (pma) is a potent mitogen for human peripheral blood lymphocytes (PBL) comparable to phytohemagglutinin (PHA) in potency. Inactivation of PHA-responsive lymphocytes by 5'-bromodeoxyuridine and light treatment left the PMA response intact and nice versa. Experiments separating lymphocytes by rosetting with sheep erythrocytes (SRBC) demonstrated that the PMA-responsive lymphocytes segregate with those that have a high affinity for SRBC to a greater than PHA- or concanavalin A (Con A)-responsive cells. These results indicate that a PMA-responsive population in human peripheral blood resides within the T-lymphocyte population and appears to have a high affinity for SRBC and to be distinct from that responding to PHA and Con A. PMA may be useful clinically to assay the size and function of the high affinity or "active" rosette population.

Animals↗
PubMed1976

Effects of concanavalin A and a succinylated derivative on lymphocyte proliferation and cyclic nucleotide levels.

To better define cell surface-related changes involved in lymphocyte activation, we studied native concanavalin A (Con A) and succinylated concanavalin A (Suc-Con A) for their effects on proliferation and cyclic nucleotide levels of human peripheral blood lymphocytes. At optimal mitogenic concentrations, the two forms of Con A induce equivalent proliferation; however, the mitogenic activity of Con A progressively decreases above 50 mug/ml. In contrast, the mitogenic activity of Suc-Con A is not decreased even at 250 mug/ml.

Cell Division↗
PubMed1976

Isoprinosine augmentation of phytohemagglutinin-induced lymphocyte proliferation.

The need for agents designed to modify immune response in the treatment of patients with viral infection, immunodeficiency, or cancer prompted the present study on the mechanisms of action of isoprinosine, a compound developed for antiviral use and whose therapeutic activity may involve the immune system. The effect of isoprinosine on in vitro proliferation of human peripheral blood lymphocytes stimulated by phytohemagglutinin (PHA) and on lymphocyte levels of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate was analyzed. Over a concentration range from 0.2 to 250 mug/ml, isoprinosine augmented PHA-induced proliferation; maximal stimulation was observed between 25 to 50 mug/ml. Isoprinosine in the absence of PHA had no effect on proliferation. The relative lack of effect of isoprinosine during a 90-min exposure and the lack of effect on lymphocyte cyclic nucleotide levels indicate that isoprinosine potentiates the PHA response by a mechanism different than a number of hormonal agents and such immunopotentiators as levamisole, polyadenylic-acid, and endotoxin. Further evaluation of isoprinosine as an immunopotentiator is indicated.

Cyclic AMP↗
PubMed1976

5-bromodeoxyuridine-light inactivation of human lymphocytes stimulated mitogens and allogeneic cells: evidence for distinct T-lymphocyte subsets.

The study of human peripheral blood currently permits enumeration of circulating B and T lymphocytes as well as the analysis of functional responses in vitro following stimulation with mitogens, antigens or allogeneic cells. In the present experiments, subsets of these major lymphocyte populations were analyzed by dissecting in vitro responses using an ablative technique. After an initial culture period of lymphocytes with a mitogen, the proliferating cells were inactivated with 5-bromodeoxyuridine and light, then the capacity of the remaining lymphocytes to respond to the same or a different mitogenic influence was tested. Responsiveness to a different stimulant in the presence of no further response to the first stimulant was taken as evidence for a different responding cell population. A large subset of peripheral blood lymphocytes was responsive to both phytohemagglutinin (PHA) and concanavalin A (Con A); ablation of the cells responsive to one left little or no cells responsive to the other. Pokeweed mitogen (PWM) stimulated a portion of the PHA-Con A-responsive subset and an approximately equal subset unresponsive to PHA or Con A. Other evidence indicates that with each of these mitogens (especially with PHA and Con A in a soluble form), most of the proliferative response of peripheral blood B lymphocytes is indirectly triggered and is dependent on T cell stimulation. The population of PHA-Con A-responsive cells is, therefore, interpreted to represent a major T cell subset plus recruited cells; the PWM-responsive population would include a T cell subset having also PHA and Con A responsiveness, and another subset of T (or perhaps B) cells. The mitogen-sensitive population showed no overlap with cells responsive to allogeneic stimulation in mixed leukocyte culture. Ablation of the mitogen-responsive cells potentiated the mixed leukocyte reaction, suggesting that a suppressive influence was removed with the inactivation of the mitogen-responsive cells. It appears, therefore, that distinct subsets of T lymphocytes differentially responsive to PHA-Con A, to PWM and to allogeneic stimulation are present in the human peripheral blood.

B-Lymphocytes↗
PubMed1975

Norepinephrine stimulation of lymphocyte ATPase by an alpha adrenergic receptor mechanism.

The effects of norepinephrine in interaction with adrenergic blocking compounds were studied on membrane adenosine triphosphatase (ATPase) activities of human lymphocytes and lymphoblasts. Sodium-potassium ion exchange pump activity was assayed by 86-Rb uptake and ATPase activity of membrane fractions was assayed by ADP and inorganic phosphate generation. The results of these studies indicate that norepinephrine acts by an alpha adrenergic mechanism to enhance membrane sodium-potassium ion exchange pump activity and ATPase activity. The pharmacologic and ionic dissection of the adrenergic sensitivity of ATPase activity indicates that this alpha adrenergic mechanism is related to membrane ATPase activities in addition to that associated with the ion exchange pump. Analysis of fractions obtained by sucrose gradients indicates that the action of norepinephrine is localized in the plasma membrane. Beta adrenergic stimulation was observed to inhibit ATPase activity. The complexity of adrenergic effects on membrane ATPase suggests interactions of hormone modulation of membrane nucleotide cyclases and transport-related ATPase enzymes.

Biological Transport↗
PubMed1972

Guanosine 3':5'-cyclic monophosphate: a possible intracellular mediator of mitogenic influences in lymphocytes.

Adenosine 3':5'-cyclic monophosphate (cyclic AMP) has been shown to have an antimitotic role in various cell types, and it has been hypothesized that a decrease of cyclic AMP concentration in the cell initiates or permits cell division. This hypothesis has been evaluated with respect to clonal proliferation of lymphocytes. Two potent mitogenic agents, phytohemagglutinin and concanavalin A, which induce thymic-dependent lymphocytes to undergo clonal proliferation, were examined for their ability to initiate proliferation and to alter the concentrations of cyclic AMP and guanosine 3':5'-cyclic monophosphate (cyclic GMP) in purified human peripheral blood-lymphocytes. Optimal mitogenic concentrations of phytohemagglutinin and concanavalin A produced 10- to 50-fold increases in the concentration of lymphocyte cyclic GMP within the first 20 min of exposure to the mitogens. No changes were seen in the concentration of cyclic AMP after stimulation with either mitogen in purified form. Increases of less than 2-fold in the concentration of lymphocyte cyclic AMP observed with a less purified preparation of phytohemagglutinin could be attributed to the agglutinating rather than the mitogenic properties of the mitogen. A revised hypothesis is presented in which a temporally discrete rise in lymphocyte cyclic GMP concentration is viewed as an active signal to induce proliferation, while the elevation of cyclic AMP concentration in these cells is viewed as a regulatory influence that limits or inhibits mitogenic action.

Agglutination↗