Two novel TSC2 mutations in Chinese patients with tuberous sclerosis complex and a literature review of 20 patients reported in China.
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Adult↗
Biomedical subjects
H L Zhou
Publications and source records attributed to H L Zhou.
Nondipole effects in the photoionization of xe 4d5/2 and 4d3/2: evidence for quadrupole satellites.
Measurements of nondipole parameters in spin-orbit-resolved Xe 4d photoionization demonstrate dynamical differences arising from relativistic effects. The experimental data do not agree with relativistic random-phase approximation calculations of single ionization dipole and quadrupole channels. It is suggested that the discrepancy is due to the omission of multiple-excitation quadrupole channels, i.e., quadrupole satellite transitions.
Journal Article↗
Absolute measurements and theoretical calculations of photoionization cross sections along the isonuclear sequence of multiply charged barium ions.
Photoionization of multiply charged ions of the Ba isonuclear sequence up to Ba6+ has been studied in a beam-beam experiment. A very strong increase in the resonance structures was observed when moving from Ba2+ to Ba6+. Absolute values of the photoionization cross sections were measured for Ba2+ and Ba3+ ions. The interpretation of the results is provided using theoretical multiconfiguration Dirac-Fock and relativistic random phase approximation calculations, showing that the collapse of the nf orbitals occurs for Ba4+.
Journal Article↗
K-shell photodetachment of Li(-): experiment and theory.
An experimental K-shell photodetachment study of Li(-) giving rise to doubly photoionized Li(+) ions has been carried out at the Advanced Light Source, using a collinear photon-ion beam apparatus. The experiment reveals dramatic structure, differing substantially both qualitatively and quantitatively from the corresponding processes above the 1s ionization threshold in Li and Li(+), as predicted by our enhanced R-matrix calculation. The experimental/theoretical comparison shows good agreement over some of the photon energy range, and also reveals some puzzling discrepancies.
Journal Article↗
Effects of methylprednisolone and aprotinin on phospholipase D activity of leukocytes in systemic inflammatory response induced by cardiopulmonary bypass.
AIM: To investigate the role of leukocyte phospholipase D (PLD) in systemic inflammatory response induced by cardiopulmonary bypass (CPB) and the effects of methylprednisolone and aprotinin on leukocyte PLD activity. METHODS: Forty-two patients who received CPB open heart surgery were divided into 3 groups: methylprednisolone group, aprotinin group, and control group. Arterial blood (10 mL) was collected for assay of leukocyte PLD activity, myeloperoxidase (MPO) activity, and CD11b expression at 8 different time points in perioperative period. Plasma IL-6, IL-8, and C-reactive protein levels were also determined. RESULTS: At the time point of ascending aorta declamped, leukocyte PLD activity for control group was (18 +/- 8) nmol choline . h-1 . mg-1, which was higher than that of pre-CPB (P < 0.01); the PLD activity for methylprednisolone group was (10 +/- 6) nmol choline . h-1 . mg-1 that was lower than control (P < 0.05), while it had no statistical difference compared with that of pre-CPB. In methylprednisolone group, PLD activity elevation was postponed to the time point of CPB stopped. There was no statistical difference in PLD activity between aprotinin group and control (P > 0.05). After administration of methylprednisolone or aprotinin, leukocyte CD11b expression, plasma IL-6, IL-8, C-reactive protein levels, and MPO activity decreased by different extent. CONCLUSION: Leukocyte PLD activity was elevated significantly in systemic inflammatory response induced by CPB and methylprednisolone partially blunted the CPB-induced inflammatory response by inhibiting PLD activity.
Adolescent↗
[Role of phospholipase D in phagocytosis and exocytosis].
Mammalian phospholipase D(PLD) is a very important enzyme in the cellular signalling pathways. More and more lines of evidences suggest that PLD may be pivotal on multiple specialized steps in receptor-mediated phagocytosis and exocytosis. In this review, we will explore the recent advances on the role and the mechanism of PLD in phagocytosis and exocytosis.
Animals↗
Does aluminum inhibit pollen germination via extracellular calmodulin?
The effect of aluminum (Al) on pollen germination and its mechanism of action were investigated. Pollen germination and pollen tube elongation were inhibited by Al at pH 4.5. This inhibitory effect was reversed by the addition of purified calmodulin (CaM), whereas neither the calcium binding-protein S-100 nor Al chelator citric acid at the same concentrations had any obvious effect on Al-inhibited pollen germination. The presence of either the membrane-impermeable CaM inhibitor anti-CaM antiserum or Ca2+ chelator EGTA completely suppressed the effect of exogenous CaM. These results indicate the involvement of extracellular calmodulin in the short-term effects of Al on pollen germination and pollen tube elongation.
Aluminum Chloride↗
[Phospholipase D and inflammation].
Phospholipase D (PLD) is widely distributed in mammalian cells, where it is regulated by a variety of extracellular signals. Its major substrate is phosphatidylcholine (PC), which is hydrolyzed to phosphatidic acid (PA) and choline. The PLD-catalysed PC hydrolysis is believed to be an important mechanism of signal transduction in cells. More and more lines of evidence indicate that PLD is tightly involved in inflammation. This review introduces the recent advances of PLD in respiratory burst, degranulation and arachidonic acid release.
Animals↗
[Rolipram reversed salbutamol tolerance in guinea pig trachea].
Studies were carried out to examine the role of phosphodiesterase(PDE) III and PDE IV in the development of tachyphylaxis of isolated guinea pig trachea to beta 2 adrenoceptor agonists. Treating trachea with salbutamol(SB) 1 mumol.L-1 for 1 h produced a 5-fold rightward shift of the SB concentration-response curve for the spasmolytic effect against methacholine-induced bronchocontraction and decreased the maximum SB-induced relaxation by 30%, i.e. induced tolerance of airway response of SB in vitro. The PDE IV inhibitor rolipram (Rol, 1 mumol.L-1, IC50), but not the PDE III inhibitor siguazodan (SK&F 94836, 1 mumol.L-1, IC50), reversed the SB tolerance. However, the protein synthesis inhibitor cycloheximide(10 mumol.L-1) did not abolish the SB tolerance. These results indicate that the SB tolerance may be related to increase in PDE IV activity.
Adrenergic beta-Agonists↗
Calbindin-containing non-specific thalamocortical projecting neurons in the rat.
Immunoreactivity for calcium binding proteins was used to demonstrate the neurochemical profiles of non-specific thalamocortical neurons located in the ventromedial nucleus, the centrolateral nucleus, and the nucleus reuniens that project to the somatosensory cortex in the adult rat. Cortical injections of fluorescent tracers combined with immunohistochemistry for calcium binding proteins revealed that retrogradely labeled neurons in these three thalamic nuclei are immunoreactive for calbindin. The present results suggest the presence of a chemically distinct non-specific thalamocortical system which terminates in the neocortex.
Animals↗
Salbutamol up-regulates PDE4 activity and induces a heterologous desensitization of U937 cells to prostaglandin E2. Implications for the therapeutic use of beta-adrenoceptor agonists.
Previous studies with U937 cells, a human monocyte cell line, have shown that the activity of cyclic nucleotide phosphodiesterase 4 (PDE4) is increased by agents that elevate cyclic AMP content. The present experiments were conducted to determine 1) whether an increase in PDE4 steady-state message and/or protein accompanies the up-regulation of PDE4 activity and 2) whether the up-regulation changes the functional responses of U937 cells to activators of adenylyl cyclase. To up-regulate PDE4 activity, U937 cells were treated for 4 h with a combination of 1 microM salbutamol, a beta-adrenoceptor agonist, and 30 microM rolipram, a PDE4 inhibitor. Cells were washed extensively to remove drugs and used immediately in various experimental protocols. Reverse transcriptase-polymerase chain reactions conducted with primers specific for the four PDE4 subtypes suggested that pretreatment with salbutamol and rolipram increased steady-state mRNA levels of PDE4A and PDE4B, but not PDE4C or PDE4D. Immunoblot analyses using two rabbit polyclonal antibodies, one directed against human recombinant PDE4A and PDE4D and a second directed against human recombinant PDE4B, revealed bands of immunoreactivity corresponding to approximately 125 kDa (PDE4A) and approximately 70 kDa (PDE4B), respectively, that increased in intensity after cells were treated with salbutamol and rolipram. As demonstrated in both time course and concentration-response studies with prostaglandin E2 (PGE2), an agent that activates adenylyl cyclase by a non-beta-adrenoceptor-mediated mechanism, cAMP accumulation was substantially decreased in cells in which PDE4 activity had been up-regulated. The difference in PGE2-stimulated cAMP accumulation between control and PDE4 up-regulated cells was greatly reduced in the presence of rolipram, consistent with the notion that an increase in PDE4 activity was responsible for the heterologous desensitization. Functionally, up-regulation of PDE4 markedly decreased the ability of PGE2 to inhibit LTD4-induced Ca2+ mobilization in intact cells. A hypothetical implication of these results is that increasing PDE4 activity in vivo by administering beta-adrenoceptor agonists could exacerbate inflammatory processes by decreasing the activity of endogenous anti-inflammatory agents such as PGE2.
3',5'-Cyclic-AMP Phosphodiesterases↗
[Progress in the study of cyclic nucleotide phosphodiesterases].
There are five families of cyclic nucleotide phosphodiesterase isozymes, which have a common structure, but have different biochemical characteristics, physiologic functions and regulatory mechanisms. Various selective phosphodiesterase inhibitors may have potential uses for antiasthmatic, inotropic, vasodilative, antithrombotic and antidepressant drugs.
2',3'-Cyclic-Nucleotide Phosphodiesterases↗
Colforsin or imidazolidione potentiates cAMP elevation caused by endothelin-1 in rat aorta.
Endothelin-1 (ET-1) caused slow-developing and stable vasoconstrictions in isolated rings of rat thoracic aortae with a pD2 value of 7.55 +/- 0.10 compared to pD2 values of 9.30 +/- 0.10 and 8.36 +/- 0.30 for angiotensin II and norepinephrine, respectively. Although the potency of ET-1 was somewhat lower than those of norepinephrine and angiotensin II, the maximal tension generated by ET-1 was comparable to that of norepinephrine and considerably greater than that of angiotensin II. Incubation of aortic rings in the absence of extracellular Ca2+ or in the presence of the Ca2+ channel blocker nifedipine (100 nmol.L-1) greatly attenuated ET-1-induced vasoconstriction. ET-1 (20 nmol.L-1, approximately the ED50 for vasoconstrictions) also caused elevation of cAMP levels in aortic rings after 15 and 25 min of exposure. The cAMP phosphodiesterase inhibitor imidazolidione (Imi, Ro 20-1724, 100 mumol.L-1) potentiated the cAMP responses to ET-1. Rings incubated for 25 min with ET-1 (20 nmol.L-1) showed much larger cAMP elevations caused by colforsin (Col, forskolin 1 mumol.L-1), a direct adenylate cyclase activator and potentiator, than with Col or ET-1 alone. Therefore, ET-1 may utilize at least 2 signal transduction mechanisms, one involving the opening of nifedipine-sensitive Ca2+ channels and the other involving the elevation of cAMP levels, to produce the unusually slow-developing and stable vasoconstrictions in rat aortae.
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
Association between leukotriene B4-induced phospholipase D activation and degranulation of human neutrophils.
We have explored the role of phospholipase D (PLD) activation in leukotriene B4 (LTB4)-induced Ca2+ mobilization and degranulation of human neutrophils. Stimulation of [3H]alkyl-acyl-phosphatidylcholine-labeled neutrophils with LTB4 resulted in a rapid accumulation of [3H]alkyl-phosphatidic acid (PA) as well as a somewhat slower accumulation of [3H]alkyl-diglyceride (DG). In the presence of ethanol, PLD catalyzed a transphosphatidylation reaction in which LTB4 increased [3H]alkyl-phosphatidylethanol formation and simultaneously decreased LTB4-induced PA and DG accumulation. This pattern of lipid metabolism is consistent with the conclusion that LTB4 stimulates PLD activity in human neutrophils. Additional studies in which the extracellular and intracellular concentrations of Ca2+ were varied indicated that maximal LTB4-induced PLD activation was dependent upon Ca2+ and potentiated by inhibitors of protein kinase C. The time-course and concentration-response curves for LTB4-induced PLD activation were different from those for LTB4-induced Ca2+ mobilization, as measured by fura-2 fluorescence. On the other hand, the concentration-response curve for LTB4-induced PLD activation was similar to that for LTB4-induced degranulation. Preincubation of the cells with ethanol inhibited LTB4-induced PA and DG accumulation, as well as degranulation, suggesting that one or both of these metabolites were important for this response. In contrast, ethanol had no effect on LTB4-induced Ca2+ mobilization. Propranolol, an inhibitor of phosphatidate phosphohydrolase, abolished DG accumulation in response to LTB4 but had no effect on degranulation, suggesting that PA is more important than DG as a mediator of degranulation. Taken collectively, these data indicate that LTB4-induced activation of PLD in human neutrophils is mediated by a Ca(2+)-dependent mechanism, but not by protein kinase C. In addition, PLD activation in these cells may induce degranulation, but not Ca2+ mobilization.
Alkaloids↗
Agonist-related differences in the relationship between cAMP content and protein kinase activity in canine trachealis.
We investigated the relationships between relaxation, cyclic AMP (cAMP) accumulation and cAMP-dependent protein kinase (cAMP-PK) activity in canine tracheal smooth muscle. In time course and concentration-response studies, forskolin and isoproterenol elicited relaxation of isolated trachealis strips that was accompanied by an increase in cAMP content and an activation of cAMP-PK. Although these results were consistent with the proposal that cAMP is a second messenger mediating relaxation of airway smooth muscle, close inspection of the data revealed a discrepancy in the relationship between cAMP accumulation and relaxation. To induce equivalent degrees of tracheal relaxation, forskolin generated greater increments in cAMP accumulation than did isoproterenol. On the other hand, the activation state of cAMP-PK correlated reasonably well with relaxation regardless of which agonist was used. Further analysis of the data revealed that the apparent disparity between cAMP accumulation and relaxation could largely be explained at the level of the relationship between cAMP content and cAMP-PK activity: compared to isoproterenol, forskolin induced greater increases in cAMP accumulation to achieve the same activation state of cAMP-PK. These observations lend support to the proposal that in canine trachealis, various components of the cAMP/cAMP-PK cascade exist in distinct subcellular compartments such that not all of the cAMP generated in response to forskolin has access to its target enzyme, cAMP-PK.
Animals↗
Stimulation of beta adrenoceptors in a human monocyte cell line (U937) up-regulates cyclic AMP-specific phosphodiesterase activity.
Experiments were conducted using undifferentiated U937 cells, a human monocytic cell line, to establish an in vitro model to examine the hormonal regulation of the cyclic AMP (cAMP)-specific phosphodiesterase (PDE IV). Standard chromatographic techniques, coupled with the use of inhibitors and activators that are selective for various phosphodiesterase (PDE) isozymes, were used to establish the PDE isozyme profile in supernatant fractions of U937 cells. When PDE activity was assessed using 1 microM [3H]cAMP as a substrate, 70 to 90% of the total U937 cell supernatant activity in the major peak eluting from anion-exchange columns was inhibited by 30 microM rolipram, a selective inhibitor of PDE IV. The remaining activity was nearly abolished by 10 microM siguazodan or 10 microM cyclic GMP (cGMP,) selective inhibitors of the cGMP-inhibited PDE. Kinetic analyses of the enzyme activity contained within this major peak of PDE activity revealed a cAMP Km = 3 microM and a rolipram Ki = 0.5 microM, values characteristic of PDE IV. Additional studies revealed the presence of a small amount of Ca++/calmodulin-stimulated PDE, but no cGMP-stimulated PDE or cGMP-specific PDE activity. In an effort to induce PDE activity in intact U937 cells by producing a sustained increase in cAMP content, cells were treated for 4 hr with salbutamol (1 microM), rolipram (30 microM) or a combination of both agents. The combination of salbutamol and rolipram produced a 2- to 3-fold increase in PDE activity in U937 cells; when used alone, rolipram was without effect whereas salbutamol induced an increase that was approximately one-half of that observed with the combination. Isozyme isolation and characterization revealed that the overall elevation of cellular PDE activity could be accounted for by a 2- to 3-fold increase in the Vmax of PDE IV with no change in its Km. The induction of PDE IV by salbutamol was: 1) concentration- and time-dependent; 2) detectable only after prolonged (2-4 hr) agonist exposure; 3) preceded by an increase in cAMP content and an activation of cAMP-dependent protein kinase; 4) mimicked by 8-bromo-cAMP and prostaglandin E2; 5) reversible within 3 hr of salbutamol removal; and 6) abolished by cycloheximide or actinomycin D. Collectively, these results indicate that the major PDE isozyme in the soluble fraction of U937 cells is PDE IV and that the activity of this enzyme is increased markedly in cells after prolonged exposure to agents that increase cAMP content.
3',5'-Cyclic-AMP Phosphodiesterases↗
Calcitonin gene-related peptide (CGRP)-induced cyclic AMP, cyclic GMP and vasorelaxant responses in rat thoracic aorta are antagonized by blockers of endothelium-derived relaxant factor (EDRF).
The mechanism of CGRP-induced vasodilation in rat thoracic aorta was investigated using antagonists of the classical endothelium-derived vasorelaxant factor (EDRF) and comparisons with acetylcholine-induced vasodilations. The CGRP-induced relaxations of isolated rings of rat thoracic aorta were completely dependent on the presence of endothelium and were associated with increases in the levels of both cyclic AMP and cyclic GMP, the same as in our previous study using rat abdominal aorta. Maximum relaxations to CGRP, which represented 40-50% reversal of the norepinephrine-induced contractions, occurred with 100 nM CGRP. Addition of acetylcholine (ACh, 1 microM) to aortic rings, which were already maximally relaxed to CGRP, caused further relaxation to 100%, suggesting that CGRP may use a mechanism (or pool of EDRF) different from that of ACh. Both CGRP- and ACh-induced relaxations of aorta were significantly inhibited by the EDRF blocking agents, hemoglobin (10 microM), methylene blue (10 microM), and nordihydroguaiaretic acid (NDGA, 10 microM). In fact, hemoglobin and NDGA were more effective as inhibitors of CGRP-induced relaxations than ACh-induced relaxations. Hemoglobin, methylene blue and NDGA also inhibited the CGRP-induced increases in both cyclic AMP and cyclic GMP levels. On the other hand, indomethacin, a cyclo-oxygenase inhibitor, did not alter CGRP-induced vasorelaxations or increases in either cyclic AMP or cyclic GMP levels, suggesting that prostaglandins are not involved. Therefore, CGRP-induced vasodilations in rat thoracic aorta appear to involve EDRF, leading to cyclic GMP elevations in smooth muscle and ultimately vasorelaxations. However, another previously undescribed mechanism, which involves EDRF-dependent and indomethacin-resistant elevations of cyclic AMP levels, is triggered by CGRP in thoracic aorta. This novel EDRF-dependent cyclic AMP response may contribute to the CGRP-induced vasodilation in rat thoracic aorta.
Acetylcholine↗
Effect of H-8, an isoquinolinesulfonamide inhibitor of cyclic nucleotide-dependent protein kinase, on cAMP- and cGMP-mediated vasorelaxation.
We theorized that H-8, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide, an inhibitor of cyclic nucleotide-dependent protein kinases, might be a useful probe to assess cyclic nucleotide-dependent relaxation of blood vessels. However, working in the rat caudal artery and aorta, we found that neither cyclic AMP- nor cyclic GMP-mediated relaxations were diminished by even large doses of H-8. For example, in the caudal artery, relaxation of a phenylephrine contraction by 8-bromo-cGMP (10(-5) M) was unaffected by H-8: control, 33 +/- 6.2%; 10 microM H-8, 41 +/- 12%; 30 microM H-8, 30 +/- 16% (p NS). The amount of relaxation by 8-bromo-cAMP (3 x 10(-4) M) was actually increased by H-8: control, 29 +/- 7.6%; 10 microM H-8, 34 +/- 7.4%; 30 microM H-8, 80 +/- 14%. In the rat aorta, H-8 also failed to diminish relaxation induced by 8-bromo-cGMP, or by atriopeptin II or sodium nitroprusside. In both caudal artery and aorta, H-8 of itself caused a dose-dependent suppression of alpha-adrenergic contraction: for example, in the caudal artery, with 10 or 30 microM H-8, peak contraction to phenylephrine was reduced to 70 (SEM) +/- 12% or 52 +/- 7% of control, respectively. The results suggest that the protein kinase inhibitor H-8 is not a useful probe to study cyclic nucleotide-dependent relaxation.
Animals↗