Search

1. The actions of diazoxide and minoxidil sulphate have been compared with those of cromakalim in rat aorta and portal vein. 2. Diazoxide and minoxidil sulphate hyperpolarized the rat portal vein in a similar manner to cromakalim. 3. Cromakalim, diazoxide and minoxidil sulphate increased 42K and 86Rb efflux from rat portal vein, although minoxidil sulphate had only a small effect on 86Rb efflux. 4. Cromakalim, diazoxide and minoxidil sulphate increased 42K efflux from rat aorta but only cromakalim and diazoxide increased 86Rb efflux from this tissue. 5. Glibenclamide inhibited the relaxant actions of cromakalim, diazoxide and minoxidil sulphate on rat aorta and the increase in 42K efflux produced by these agents in this tissue. 6. Diazoxide relaxed an 80 mM KCl-induced contraction of rat aorta, whilst cromakalim and minoxidil sulphate were without effect. 7. Cromakalim, diazoxide and minoxidil sulphate had no effect on cyclic AMP or cyclic GMP concentrations in rat aorta. 8. It is concluded that diazoxide and minoxidil sulphate like cromakalim exhibit K+ channel opening properties in vascular smooth muscle. Diazoxide exerts an additional inhibitory action not related to the production of cyclic AMP or cyclic GMP. The action of minoxidil sulphate may be primarily located at a K+ channel which is relatively impermeable to 86Rb.

Cromakalim, pinacidil, nicorandil, diazoxide and RP-49356 belong to the class of drugs termed potassium channel openers. In rat portal vein diazoxide, like cromakalim, abolished spontaneous mechanical and electrical activity and in rat aorta caused an increase in 86Rb efflux and inhibited KCl(20 mM)-induced contractions. However, in contrast to cromakalim, diazoxide (greater than 100 microM) also inhibited mechanical responses evoked by 80 mM KCl in rat aorta suggesting that it possesses pharmacological properties in addition to K channel opening. Since glibenclamide can attenuate the effects of cromakalim and diazoxide in vascular tissues, it is possible that a channel resembling the ATP-sensitive K channel found in pancreatic beta-cells may be involved in the vasorelaxant effects of these agents. However, differences exist in the order of potency of cromakalim and diazoxide for producing smooth muscle relaxation and for decreasing insulin secretion in pancreatic beta-cells. Furthermore galanin (which opens ATP-sensitive K channels in beta-cells) increases mechanical activity in rat portal vein. It is anticipated that new chemical developments will produce K channel opening molecules with greater potency and tissue selectivity.

Surface immunoglobulin on spleen cells from NZB and NZB/W mice and congenic mice bearing the nude or X-linked immune defective (Xid) gene was examined by flow microfluorometry with regard to both the frequency of positive cells and density expressed on the cell. These data indicate that although the frequency of unseparated sIg+ B lymphocytes is equivalent among all of these groups of mice, the densities of sIgM and sIgD are different. Spleen cells from these mice were also separated by free-flow electrophoresis and analyzed in a similar manner. This analysis demonstrated the absence of a subpopulation of B lymphocytes with a low electrophoretic mobility and low expression of sIgM. These studies suggest that maturational and/or activation states of the B cells in mice bearing the Xid or nude genes are different from those seen in the parent strains of mice. Such alterations in cell-surface antigens correlate with the differences in the natural history of immunopathology of the autoimmune disease in these congenic colonies of New Zealand mice.

The production of autoantibodies to erythrocytes by immunization with rat red blood cells (RRBC) is significantly retarded in X-linked immune deficient (Xid) mice. We have attempted to further explore this relationship by characterizing RRBC-induced erythrocyte autoantibodies in high responder New Zealand Black (NZB) and congenic NZB.Xid mice. NZB.Xid animals, immunized with RRBC, readily produce anti-RRBC antibodies and cross-reactive antiautologous erythrocyte antibody (CR anti-MRBC) as well as anti-HB antibodies. The autoantibody response of NZB.Xid mice to RRBC appears similar to NZB controls with respect to both the time of onset and subclass diversity; the anti-HB antibody cannot be absorbed with RRBC. Moreover, there are no alterations in the spectrotype of antierythrocyte antibodies found in NZB.Xid mice. Nonetheless, NZB.Xid, but not NZB mice, fail to produce splenic plaque-forming responses against bromelase-treated mouse red blood cells. Lyb 5+ cells are not required for the production of RRBC-induced antierythrocyte autoantibodies. These results, when discussed in light of the low but significant incidence of spontaneous DAT in NZB.Xid mice, suggest that given the appropriate genetic repertoire, the influence of the Xid gene on autoantibody production can be bypassed.

CA-549 is a circulating breast cancer-associated antigen that reacts with monoclonal antibody BC4E 549. Biochemical characterization of CA-549 revealed that it is an acidic (isoelectric point 5.2) glycoprotein that exhibits two bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions of apparent molecular weights of 400,000 and 512,000. Immunohistochemical staining of unfixed frozen tissue sections of human breast tumors and a variety of benign tissues with BC4E 549 revealed no preferential staining of tumor over benign breast tissue and cross-reactivity with a wide range of other benign tissues including kidney, liver, lung, colon, pancreas, ovary, and spleen. Serum levels of CA-549 were initially tested by an enzyme-linked immunosorbent assay inhibition using BC4E 549. This assay showed that CA-549 concentrations were elevated in 19 of 27 sera from patients with advanced breast cancer compared to 0 of 22 and 0 of 129 sera from benign breast disease patients and healthy females, respectively. These preliminary data suggested that CA-549 was a useful breast tumor marker; thus BC4E 549 was adapted to a sandwich immunoradiometric assay format suitable for routine use in the clinical laboratory and its performance was evaluated on a panel of 668 serum samples. The test detected significant concentrations of CA-549 in the sera of 40 of 80 patients with advanced breast cancer, 1 of 30 with early breast cancer, 4 of 19 with advanced lung cancer, 2 of 40 with advanced colon cancer, and 5 of 29 with advanced prostate cancer. The test showed a high degree of specificity, producing false-positives in only 3 of 79 benign breast patients, 2 of 25 benign liver patients, 2 of 70 benign colon patients, 2 of 19 benign lung patients, 0 of 20 benign prostate patients, and 3 of 257 healthy individuals. These data represent an overall 50% sensitivity and 98% specificity as a test for advanced breast cancer. These data indicate that this immunoradiometric assay is a useful test for the detection of circulating CA-549 in advanced breast cancer patients and suggest that it may prove useful as a monitor in the management of that disease.

In rat portal vein and aorta, pinacidil (0.3-100 microM) inhibited spontaneous mechanical activity (portal vein) and responses to norepinephrine (0.001-100 microM) and to KCl (5-80 mM). Pinacidil and its analogs P1060 and P1368 inhibited established contractions to 20 mM KCl but had little effect on responses to 80 mM KCl. The order of spasmolytic potency was P1060 greater than pinacdil greater than P1368. Intracellular electrical recording showed that in a portal vein, pinacidil (0.3-10 microM) abolished spontaneous electrical activity and hyperpolarised the cells to the region of the calculated EK. Pinacidil (3-10 microM) produced a similar hyperpolarisation in rat aorta, and in both tissues the hyperpolarisation was maintained in the continuing presence of pinacidil. Using 86Rb as a K+ marker, pinacidil increased 86Rb exchange in both the rat portal vein and aorta. The analog P1060 also increased 86Rb efflux in the rat portal vein; P1368 had no significant effect. It is concluded that the inhibitory effects of pinacidil in rat blood vessels are associated with the opening of 86Rb-permeable K+ channels. This mechanism produces a low-resistance pathway in the membrane and this inhibits the ability of pressor agents to produce smooth muscle contraction.

The effects of pinacidil have been compared with those of glyceryl trinitrate (GTN) using the aorta and portal vein of the rat and the trachealis and taenia caeci of the guinea-pig. In aorta, both pinacidil and GTN inhibited responses to noradrenaline and showed some selective inhibition of contractions to 20 mM K+. Responses to 80 mM K+ were little affected. In trachealis, both pinacidil and GTN inhibited spontaneous tone and selectively relaxed spasms to 20 mM K+. Responses to 80 mM K+ were unaffected. In portal vein, pinacidil completely inhibited spontaneous electrical and mechanical activity. GTN reduced the amplitude of tension waves and extracellularly-recorded discharges, but increased the frequency of spontaneous electrical and mechanical activity. In portal vein, pinacidil inhibited contractions to noradrenaline and selectively inhibited responses to 20 mM K+. GTN had little inhibitory effect on responses to either noradrenaline or K+. In portal veins loaded with 86Rb as a K+-marker, pinacidil significantly increased the 86Rb efflux rate coefficient whilst GTN had no effect on 86Rb exchange. In taenia caeci, both pinacidil and GTN inhibited the spontaneous tone of the preparation. These inhibitory effects were not antagonized by apamin. It is concluded that pinacidil and GTN do not share a common relaxant mechanism. Evidence has been obtained that pinacidil exerts its inhibitory effects by the opening of apamin-insensitive, 86Rb-permeable K+ channels.

In rat aorta and rat portal vein, (-)- and (+)-pinacidil each produced a concentration-dependent inhibition of tension development. Although the (-) isomer was the more potent, concentration effect curves for each isomer were steep with similar slopes. In rat portal vein, tetraethylammonium and procaine antagonised the relaxant effect of (+/-)-pinacidil, whereas 3,4-diamino-pyridine was without effect. Intracellular microelectrode recording in rat portal vein showed that low concentrations of (+/-)-pinacidil reduced the duration of multispike electrical complexes. In both rat aorta and rat portal vein, higher concentrations of (+/-)-pinacidil hyperpolarised the membrane towards the potassium equilibrium potential. (+/-)-Pinacidil increased 86Rb efflux from rat aorta and rat portal vein in a concentration dependent manner. In a separate study, (+/-)-pinacidil increased 42K efflux from rat portal vein. (+/-)-Pinacidil had no effect on cyclic GMP or cyclic AMP levels in rat aorta. It is concluded that pinacidil opens 86Rb-permeable potassium channels in rat aorta and rat portal vein. This mechanism is independent of cyclic nucleotide changes and may be responsible for the antihypertensive effect of pinacidil.

In recent years, management responsibilities at the unit level have expanded considerably. In this evolution of the nurse-manager role, the importance of the planning process in the overall productivity and success of the unit has gained widespread acceptance. To meet the challenges of today's health care climate, the nurse manager and the unit staff must have a clear understanding of what our business is, what it should be, and finally, depending on the plans developed, what it will be.

1. Leukocytosis- and lymphocytosis-stimulating activity was present in fluid cultures of B. pertussis. The activity was found primarily in the culture supernatant fluid. 2. The sequential changes in the leukocyte response were similar to those previously observed following injection of intact bacteria into mice. 3. Activity was destroyed by heat and was diminished, but not abolished, by prolonged treatment with proteolytic enzymes. 4. A water-insoluble fraction of the culture supernatant fluid was isolated which contained virtually all of the activity. The specific activity was more than 100-fold greater than that of the intact bacteria, and injection of microgram quantities produced a response. 5. The distribution of histamine-sensitizing factor followed that of leukocytosis-stimulating activity. In contrast, mouse protective antigen was localized to the bacterial pellet.