Suppression of pulmonary and systemic vascular histamine H2-receptors in allergic sheep

We have previously demonstrated a depression of airway H2-receptor function in sheep allergic to Ascaris suum antigen. To investigate whether this is a generalized defect, we studied the H1- and H2- histamine receptor functions in the pulmonary and systemic circulations of allergic and nonallergic sheep. Pulmonary arterial pressure, and cardiac output were measured for calculation of pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) before and immediately after a rapid intrapulmonary infusion of histamine (10 micrograms/kg), with and without pretreatment with H1- (chlorpheniramine) and H2- (metiamide) antagonists. Histamine alone increased mean PVR to 435 and 401% of base line and decreased mean SVR by 51 and 54% in the nonallergic and allergic sheep, respectively (P less than 0.001). In the nonallergic sheep following pretreatment with chlorpheniramine (selective H2 stimulation) or metiamide (selective H1 stimulation), histamine decreased SVR by 18 and 36%, respectively, suggesting that approximately two-thirds of the vasodepressor response was mediated by H1-receptors and one-third by H2-receptors. Combined H1- and H2-antagonists completely blocked the histamine response. In allergic sheep the histamine-induced decrease in SVR was primarily mediated by H1-receptors, because the response was blocked by H1-antagonist, chlorpheniramine, and the H2-antagonist, metiamide, had no effect. In the pulmonary circulation selective H1-stimulation caused a similar increase in PVR in allergic (365%) and nonallergic sheep (424%), whereas selective H2-stimulation caused a significant decrease in PVR in the nonallergic group (14%) but not in the allergic group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of high affinity binding sites for charybdotoxin in sarcolemmal membranes from bovine aortic smooth muscle. Evidence for a direct association with the high conductance calcium-activated potassium channel

Charybdotoxin (ChTX), a peptidyl inhibitor of the high conductance Ca2+-activated K+ channel (PK,Ca), has been radiolabeled to high specific activity with 125I, and resulting derivatives have been well separated. The monoiodotyrosine adduct blocks PK,Ca in vascular smooth muscle with slightly reduced potency compared with the native peptide under defined experimental conditions. [125I]ChTX, representing this derivative, binds specifically and reversibly to a single class of sites in sarcolemmal membrane vesicles prepared from bovine aortic smooth muscle. These sites display a Kd of 100 pM for the iodinated toxin, as determined by either equilibrium or kinetic binding analyses. Binding site density is about 500 fmol/mg of protein in isolated membranes. The addition of low digitonin concentrations to disrupt the vesicle permeability barrier increases the maximum receptor concentration to 1.5 pmol/mg of protein, correlating with the observations that ChTX binds only at the external pore of PK,Ca and that the membrane preparation is of mixed polarity. Competition studies with ChTX yield a Ki of about 20 pM for native toxin. Binding of [125I]ChTX is modulated by ionic strength as well as by metal ions that are known to interact with PK,Ca. Moreover, tetraethylammonium ion, which blocks PK,Ca with moderately high affinity when applied at the external membrane surface, inhibits [125I]ChTX binding in an apparently competitive fashion with a Ki similar to that found for channel inhibition. In marked contrast, agents that do not inhibit PK,Ca in smooth muscle (e.g. tetrabutylammonium ion, other toxins homologous with ChTX, and pharmacological agents that modulate the activity of dissimilar ion channels) have no effect on [125I]ChTX binding in this tissue. Taken together, these results suggest that the binding sites for ChTX which are present in vascular smooth muscle are directly associated with PK,Ca, thus identifying [125I]ChTX as a useful probe for elucidating the biochemical properties of these channels.     

A comparative investigation of neuroglia in representative vertebrates: a silver carbonate study

The phylogenetic development of neuroglia (astrocytes, oligodendrocytes) was investigated in homologous cortical and subcortical forebrain regions of selected vertebrates. Microglia were not considered in the current study. Four to seven brains from each species were used. Scharenberg's modification for astroglia of del Rio Hortega's silver carbonate technique was used. The analysis of neuroglia cells was based on (1) the characteristic cellular morphology found in each species, (2) a comparison of the selected regions in each animal, (3) the interrelationships of astrocytes and their relations to neurons, blood vessels, and oligodendrocytes. The predominant type of neuroglia found in the fish, frog, and lizard was the ependymal cell; however, non-ependymal glial cells were also present. The bird represented a transitional phylogenetic stage from a predominance of ependymal glial to a predominance of non-ependymal glia. A progressive increase in the morphological relationships of glial cell bodies and processes to neurons was found with ascension of the phylogenetic scale from fish through primate. Interrelations were observed between adjacent astrocytic processes and cell bodies, and between astrocytes and oligodendrocytes. The processes of adjacent glial cells also appeared to show an increase in thickness at the point of approximation. A variety of astrocytes were observed ranging from small, round-oval shaped cells to large polygonal or stellate forms. Variations in the number of astrocytic processes, their thickness, and degree of secondary branching were described, and their possible functional significance was discussed.     

Prospective randomised controlled trial of methods of call and recall for cervical cytology screening.

OBJECTIVE--To discover whether systematic methods of call and recall are more effective than a non-systematic method and to see which of the two systematic methods was more effective. DESIGN--Prospective randomised controlled trial over a year. SETTING--One group general practice. PATIENTS--416 Women over 35 eligible for a smear test who had never had a cervical smear test or in whom a smear test was overdue (previous test more than five years before). INTERVENTIONS--One group received written invitations to have a smear taken. The second group had their notes tagged so that the doctor would remind them (when they attended for another reason) to have a smear test. No special intervention was made in the third group. MAIN OUTCOME MEASURE--Performance of a cervical smear test during the year of the study. RESULTS--32% (45/140) of the screened group, 27% (39/142) of the tagged group, and 15% (20/134) of the control group had a smear test during the year. The percentage of women having a smear test in the screened group was not significantly different from that in the tagged group, but the percentages in the two groups were significantly different from that in the control group. Whether a woman had had a previous smear test significantly affected the uptake of the invitation to have a smear test independently of the method of invitation. CONCLUSIONS--The systematic methods of call and recall were more effective than a non-systematic method. There was no significant difference between the two systematic methods (sending letters or tagging the notes) at one year.