Federation proceedings最新文献

Genetically mast cell-deficient W/Wv mice are useful for the analysis of mast cell biology, especially as recipients of bone marrow cells and skin pieces. Inasmuch as suspension and clonal cultures of mast cells have been developed, we combined these in vivo and in vitro systems. Suspension-cultured mast cells had morphological and biochemical characteristics similar to those of mucosal mast cells (MMC). However, i.p. injection of such cultured mast cells gave rise to development of cells with characteristics similar to those of connective tissue mast cells (CTMC). When peritoneal cells of normal +/+ mice were cultured in methylcellulose, pure mast cell colonies appeared. Cells from individual mast cell colonies were divided and injected into the skin and stomach wall of W/Wv mice; CTMC developed in the skin and MMC in the stomach mucosa. This indicates the presence of a common precursor for CTMC and MMC. Morphology of such bipotent mast cell precursors was studied by using micromanipulation. About 4% of morphologically identifiable peritoneal mast cells may function as the bipotent precursors. Although W/Wv mice showed a defect in resistance against ixodid ticks, injection of suspension-cultured mast cells normalized the defect. The four examples mentioned above indicate that combinations of in vivo and in vitro systems increase the usefulness of W/Wv mice.

Certain stilbene estrogens, in particular diethylstilbestrol, are established carcinogens in animals and in humans. The question is raised whether the formation of reactive metabolites is part of the carcinogenic mechanism of these compounds. Some aspects of the oxidative metabolism are briefly reviewed, with special emphasis on peroxidase-mediated metabolic activation. The interaction of the reactive intermediates with nucleic acids and proteins is described and examples of the induction of genetic damage in several short-term assays are given. From the available data it is concluded that metabolic activation may play a role in the process of neoplastic cell transformation induced by stilbene estrogens.

In the flow-regulated dog forelimb, electrical stimulation of the efferent median nerve produced frequency-dependent increases in perfusion pressure. These vasoconstrictor effects were attenuated by a large dose of phentolamine, an alpha 1 and alpha 2 blocking drug. Administration of methysergide after phentolamine completely reversed the vasoconstrictor responses to vasodilation at most frequencies of stimulation. In the absence of phentolamine pretreatment, even a lower dose of methysergide reversed or caused biphasic responses (attenuated constriction followed by dilatation) during the nerve stimulation at the lower frequencies (0.5-4.0 Hz). This lower dose of methysergide completely abolished vascular effects of exogenous 5-hydroxytryptamine (5-HT) and potentiated those of norepinephrine; hence, the antagonism by methysergide of neurally mediated vasoconstriction is not caused by an action on alpha-adrenergic receptors. Unlike methysergide, selective 5-HT2 antagonists ketanserin and ritanserin have no modifying effect on exogenous 5-HT responses. These studies have provided pharmacological evidence that suggests that 5-HT may be the neurotransmitter mediating neurogenic vasoconstriction in the dog forelimb, and that this effect does not involve activation of 5-HT2 receptors.

The patterns of vasoconstriction produced by local infusions of constrictor agents and neurogenic stimuli are unique and varied. Although vasoconstrictors or neurogenic stimuli may produce similar increases in total resistance to blood flow, the effects on consecutive vascular segments may differ dramatically. Vasoconstrictors may affect primarily small vessels, large vessels, or a combination of both. The constrictor response may be restricted to precapillary vessels or may recruit both pre- and postcapillary vessels. The baroreceptors elicit a pattern of vasoconstriction distinct from that produced by electrical stimulation of a vasomotor nerve. Prearteriolar and venous resistance may contribute more than arterioles to increases in total vascular resistance produced by local infusions of vasoconstrictor agents or nerve stimulation. The constriction of large vessels also affects fluid filtration, vascular capacity, and the distribution of blood flow between shunt and exchange vessels. The waning of the resistance increase that occurs during prolonged infusions of vasoconstrictors varies, in part, as a function of the vessel segments that participate in the vasoconstrictor response. Large vessels participate in vasoconstrictor responses triggered by stimuli that impose a severe stress on the circulation. In contrast, small vessels participate primarily in normal vascular adjustments required to maintain blood pressure at the set point.

A single cytotoxic T lymphocyte (CTL) is capable of performing the two most fundamental functions of an immune response, recognition and elimination of foreign antigens. It is now clear that in a CTL these two functions are linked via the antigen-specific, heterodimeric receptor. We review here some experimental approaches that justify this conclusion and provide the means for further examination of the mechanisms by which CTLs lyse their target cells. When antireceptor antibodies serving as antigen substitutes are attached to various cells, they trigger the lytic activity of particular CTLs, which results in lysis of the antibody-modified cell. In the process, a novel serine esterase, which is located within cytolytic granules of the CTL, is released. The presence of this enzyme and a complement-like protein, perforin, in granules of a CTL has led to the suggestion that CTLs and complement have similar cytolytic mechanisms. However, the resistance of some CTLs to lysis by other CTLs, but not to lysis by antibody-activated complement, suggests fundamental differences between cytolytic mechanisms of CTLs and complement.