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The longitudinal form factors for the low-lying collective levels ofCa have been calculated using the wavefunctions of the nucleus as a linear combination of deformed and spherical states. A large discrepancy was found between the theoretical and experimental transition probabilities. [ABSTRACT FROM AUTHOR]

In this study we investigated the role of protein kinase C (PKC) in associative learning of Apis mellifera. Changes in PKC activity induced by olfactory conditioning were measured in the antennal lobes, a brain structure involved in associative learning. Multiple conditioning trials inducing a memory different from that induced by a single conditioning trial specifically cause an increase in PKC activity. This increase begins 1 hr after conditioning, lasts up to 3 d, and is attributable to an increased level of constitutive PKC. The increased level of constitutive PKC consists of an early proteolysis-dependent phase and a late phase that requires RNA and protein synthesis. Inhibition of the pathways resulting in constitutive PKC selectively impairs distinct phases of multiple-trial induced memory. The inhibition of the proteolytic mechanism has an instant effect on an early phase of multiple-trial induced memory but does not affect acquisition and the late phase of memory. Blocking of the transient PKC activation during conditioning does not affect the induction of memory formation. Thus, the constitutive PKC in the antennal lobe seems to contribute to the early phase of memory that is induced by multiple-trial conditioning.

Studies from several laboratories have revealed that structurally diverse substances including the wasp venom, mastoparan (MP), activate purified regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins) in a receptor-independent manner, presumably by mimicking the effects of heptahelical receptors. Mast cells and differentiated HL-60 human leukemic cells are useful model systems for the analysis of receptor-independent G-protein activation. We compared the effects of 2-phenylhistamines which are cationic-amphiphilic, too, and of MP on G-protein activation in dibutyryl cAMP-differentiated HL-60 cells and in the rat basophilic leukemia cell line, RBL 2H3. In HL-60 cells, 2-phenylhistamines show stimulatory effects which resemble those of formyl peptide receptor agonists but which cannot be attributed to agonism at classical receptors. 2-phenylhistamines do not, however, activate RBL 2H3 cells and various other myeloid cell types, pointing to cell type-specificity of receptor-independent G-protein activation. In HL-60 cells, MP shows effects on G-protein activation which differ substantially from those of formyl peptides. In RBL 2H3 membranes, MP shows similar effects on G-protein activation as in HL-60 membranes. We develop a model according to which receptor-independent G-protein activation can be subdivided into direct and indirect receptor-independent G-protein activation. In case of the former mechanism, substances like 2-phenylhistamines interact with G-protein alpha-subunits and in case of the latter mechanism, substances like MP interact with nucleoside diphosphate kinase which catalyzes the formation of GTP. This newly formed GTP is then transferred to, and cleaved by, G-protein alpha-subunits.(ABSTRACT TRUNCATED AT 250 WORDS)

In dibutyryl cAMP-differentiated human leukemia (HL-60) cells, the potent histamine H1-receptor agonist, 2-(3-chlorophenyl)histamine, activates pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins) of the Gi-subfamily by a mechanism which is independent of known histamine receptor subtypes (Seifert et al. Mol Pharmacol 45: 578-586, 1994). In order to learn more about this G-protein activation, we studied the effects of histamine and various 2-substituted histamine derivatives in various cell types and on purified G-proteins. In HL-60 cells, histamine and 2-methylhistamine increased cytosolic Ca2+ concentration ([Ca2+]i) in a clemastine-sensitive manner. Phenyl- and thienyl-substituted histamines increased [Ca2+]i as well, but their effects were not inhibited by histamine receptor antagonists. 2-Substituted histamines activated high-affinity GTPase in HL-60 cell membranes in a PTX-sensitive manner, with the lipophilicity of substances increasing their effectiveness. Although HEL cells do not possess histamine receptors mediating rises in [Ca2+]i, 2-(3-bromophenyl)histamine increased [Ca2+]i in a PTX-sensitive manner. It also increased GTP hydrolysis by Gi-proteins in HEL cell membranes. All these stimulatory effects of 2-substituted histamine derivatives were seen at concentrations higher than those required for activation of H1-receptors. In various other cell types and membrane systems, 2-substituted histamine derivatives showed no or only weak stimulatory effects on G-proteins. 2-Substituted histamine derivatives activated GTP hydrolysis by purified bovine brain Gi/Go-proteins and by pure Gi2 (the major PTX-sensitive G-protein in HL-60 and HEL cells). Our data suggest the following: (1) histamine and 2-methylhistamine act as H1-receptor agonists in HL-60 cells; (2) incorporation of bulky and lipophilic groups results in loss of H1-agonistic activity of 2-substituted histamine derivatives in HL-60 cells but causes a receptor-independent G-protein-stimulatory activity; (3) the effects of 2-substituted histamine derivatives on G-proteins are cell-type specific.

Cyclosporin A (CsA) has been reported to inhibit phorbol myristate acetate (PMA)-induced superoxide anion (O2-) formation in human neutrophils and murine macrophages. We found that CsA inhibited O2- formation in HL-60 cells induced by PMA (30 nM) and phorbol dibutyrate (200 nM) with a half-maximal effect at 1 and 0.75 microM, respectively. One possible target of CsA action is protein kinase C (PKC) [EC 2.7.1.37] since phorbol esters activate this kinase. However, CsA did not inhibit PMA-mediated reduction of histamine-induced rises in cytosolic Ca2+ concentration in, and PMA-induced differentiation of, HL-60 cells and platelet aggregation. CsA did not reduce the activity of various recombinant c-PKC isoenzymes (alpha, beta 1 and gamma), n-PKC isoenzymes (delta and epsilon), an a-PKC isoenzyme (zeta) nor of PKC purified from rat brain in vitro. These data show that CsA inhibits phorbol ester-induced O2- formation in HL-60 cells but not other phorbol ester-mediated events and that inhibition by CsA of O2- formation cannot readily be attributed to direct PKC inhibition. We also show that CsA does not change the activity of nucleoside diphosphate kinase [EC 2.7.4.6] in HL-60 membranes nor the latter's physical properties.

We studied the effects of various beta-adrenoceptor (beta AR) antagonists and local anesthetics (LAs), i.e. substances possessing one basic and one lipophilic domain each, on activation of regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins). In membranes of differentiated HL-60 cells, propranolol activated high-affinity GTP hydrolysis with a half-maximal effect at 0.19 mM and a maximum at 1 mM. There was a close correlation between the log Q values (logarithm of the octanol: water partition coefficient) of beta AR antagonists and the logarithm of their effectiveness at activating GTPase (EC 3.6.1.-) in HL-60 membranes. The lipophilic LA, tetracaine, was also an effective activator of GTPase in HL-60 membranes, whereas more hydrophilic LAs were less stimulatory (bupivacaine and lidocaine) or even inhibitory (procaine). Propranolol and tetracaine also stimulated binding of guanosine 5'-O-[3-thio]triphosphate (GTP[gamma S]) to HL-60 membranes, but their stimulatory effects on GTP[gamma S] binding were smaller than on GTP hydrolysis. The stimulatory effects of propranolol and tetracaine on GTPase and GTP[gamma S] binding were inhibited by pertussis toxin. Propranolol and tetracaine effectively activated GTP hydrolysis of a reconstituted mixture of bovine brain Gi/Go-proteins, but the concentrations of substances needed for GTPase activation were higher than in HL-60 membranes. Procaine showed stimulatory effects on the GTPase of Gi/Go-proteins. Our data show that beta AR antagonists and LAs activate pertussis toxin-sensitive G-proteins, presumably through interaction with the C-terminus of their alpha-subunits. Apparently, the lipophilic domain of beta AR antagonists and LAs is more important for G-protein activation than the basic domain. We discuss the possibility that activation of nucleoside diphosphate kinase by beta AR antagonists and LAs contributes to their stimulatory effects on GTP hydrolysis in HL-60 membranes.

The results of binding studies suggest the presence of histamine H1-receptors in human monocytes, but it is not known whether these receptors are functionally active. This prompted us to study the effects of histamine (HA) on cytosolic Ca2+ concentration ([Ca2+]i) and superoxide anion (O2-) formation in HL-60 cells differentiated towards monocytes with 1 alpha,25-dihydroxycholecalciferol. In HL-60 monocytes, HA increased [Ca2+]i with a half-maximal effect at 8 microM and a maximum at 30-100 microM. Pertussis toxin (PTX) partially inhibited the stimulatory effects of HA on [Ca2+]i. Betahistine, a weak partial H1-receptor agonist, also increased [Ca2+]i, whereas H2- and H3-receptor agonists were ineffective. H1- but not H2- and H3-receptor antagonists inhibited HA-induced rises in [Ca2+]i. HA-induced rises in [Ca2+]i were desensitized in a homologous manner and were also inhibited by the activator of protein kinase C, 4 beta-phorbol 12-myristate 13-acetate. Various protein kinase C inhibitors did not interfere with homologous desensitization. The stimulatory effects of HA on [Ca2+]i were completely dependent on the presence of extracellular Ca2+ and were inhibited by the blocker of non-selective cation (NSC) channels, 1-(beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl)-1 H-imidazole hydrochloride (SK & F 96365). HA was much less effective than the chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), to induce rises in [Ca2+]i. Unlike fMLP, HA did not activate O2- formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Casework by Danish local social agencies on behalf of 11 children of chronically ill schizophrenic mothers is retrospectively analyzed, along with documentation from psychiatric hospitals, consulting child specialists, and other health professionals. Findings point to a need for earlier and more precise assessment of the mother's parenting abilities as measured against the severity of her illness and the vulnerability of her child.