Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mobilization potential”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed1990

C5a-induced neutrophilia. A primary humoral mechanism for recruitment of neutrophils.

The leukocytosis activity of C5a was studied in a rabbit model. Blood samples were drawn for cell counts through a catheter placed in an artery of one rabbit ear after injection of either porcine or human C5a into a vein in the opposite ear. These studies indicate the potential of C5a to mobilize bone marrow neutrophils following transient C5a-induced neutropenia, based on counts of nonsegmented neutrophils. The numbers of circulating neutrophils can be selectively elevated by 300% to 400%, within 1 to 2 hours, in rabbits given only microgram quantities (1 to 5 x 10(-9) mol/l) of C5a or C5adesArg. These quantities of C5a are equivalent to 1% to 2% of complement C5 activation. The time-course of the induced neutrophilia is characteristic of C5a, increasing rapidly in the first 10 to 20 minutes after injection and attaining a maximum level at 2 to 5 hours, then decreasing slowly to normal levels over the next 4 to 6 hours. After boiling at 100 degrees C for 10 minutes, C5a (C5ades Arg) lost its leukocytosis activity, indicating that the cellular effect was not caused by endotoxin. Other known leukocytosis factors, such as epinephrine, dexamethasone, lipopolysaccharide, and the prostanoid 15(S)-15-methyl PGF2 alpha, produced a distinctly different profile of leukocyte mobilization than that of C5a. The C5a-induced neutrophilia was not inhibited by pretreating these animals with indomethacin, suggesting that it is not a prostanoid-induced effect. One hypothesis is that no secondary cellular mediator system is involved in C5a-mediated leukocytosis, but rather than C5a alone is responsible for a rapid mobilization of neutrophils from bone marrow pools, and perhaps marginated pools, following neutropenia. Circulating neutrophils are activated by C5a and thereby become deformed and adherent, leading to a neutropenia, sequestration, and depletion of cells. After the neutropenic event an immediate neutrophilic response is required for replacement of this particular cell population and to re-establish homeostasis. Therefore the role of C5a may be just as important as other known leukocytosis factors (fragments from C3, for example) in promoting complement-dependent neutrophil mobilization in response to tissue injury, infections, or extracorporeal blood treatments.

Animals↗
PubMed1994

Effects of the prior activation of protein kinase C on human platelet activation induced by thrombin.

Effects of the prior activation of protein kinase C (PKC) on the responses induced by thrombin were studied using human blood platelets, in which PKC is abundantly expressed. At a concentration of 25 nM, 12-O-tetradecanoyl-phorbol 13-acetate (TPA) induced little aggregation or release by itself but selectively elicited PKC activation in a time-dependent manner, as monitored by 47-kDa protein phosphorylation. Increases in the intracellular Ca2+ concentration of human platelets caused by thrombin, at any concentration, were markedly inhibited by the prior addition of 25 nM TPA in a time-dependent manner. However, the effects of TPA on platelet aggregation and secretion induced by thrombin varied, depending upon the agonist concentration; the PKC activator markedly enhanced the aggregation and secretion induced by lower concentrations of thrombin but had a tendency to weakly inhibit those induced by higher concentrations of thrombin. TPA enhanced the ionomycin effect upon aggregation and release without obvious effects on the ionophore-induced Ca2+ mobilization, suggesting that PKC potentiates platelet function by increasing intracellular sensitivity to Ca2+. There was a good time-dependent correlation of the TPA effects among the three parameters, namely, the phosphorylation of the 47-kDa protein, inhibition of the [Ca2+]i increase induced by thrombin, and enhanced ionomycin effects in aggregation and release. It is most likely that the final responses of agonist-activated platelets depend upon the balance of two factors induced by PKC; inhibition of Ca2+ signals and enhancement of intracellular sensitivity to Ca2+.

Blood Platelets↗
PubMed1995

Frequency of atlantoaxial subluxation and neurologic involvement in patients with ankylosing spondylitis.

OBJECTIVE: To determine the prevalence of anterior and vertical atlantoaxial subluxation (AAS) and its neurological effect in a consecutive sample of Mexican patients with ankylosing spondylitis (AS). METHODS: Consecutive patients with a diagnosis of AS who attended 2 secondary care outpatient rheumatology clinic in the city of Guadalajara within a period of 6 mo were included in the study. Patients had prospective rheumatologic and neurologic assessments using structured questionnaires and examinations. Recorded variables included demographic data, disease characteristics, neurologic symptoms and signs, and axial mobility measurements. Somatosensory evoked potentials (SSEP) were performed in all patients. Patients also underwent standard cervical spine radiography with anteroposterior open mouth, and neutral, full flexion and extension lateral views. RESULTS: We studied 103 patients. Mean age was 35 yrs, 74% were male, and mean disease duration was 10 yrs (S/- SD 7.9). Anterior AAS was observed in 22 patients (21%, 95% CI 13-29%) and vertical AAS in 2 cases (2%, 95% CI 0-7%). Ossification of the posterior longitudinal ligament (OPLL) was present in 16 patients. Statistically significant associations were observed between anterior AAS and SSEP (p < 0.0001) and OPLL (p = 0.04). The degree of radiologic sacroiliitis was also associated with anterior AAS. After completion of the study, 2 patients required surgical fusion due to severe cervical cord compression. CONCLUSION: The prevalence of AAS and OPLL in this population was higher than previously reported in other settings. The association of anterior AAS with OPLL and radiological sacroiliitis could identify a subgroup of patients with more severe axial enthesopathy. Although clinically significant neurologic complications are not frequent in these patients, AAS may cause severe spinal cord compression requiring surgical fusion.

Adolescent↗
PubMed1997

[Is the immune system our sixth sense? Relation between the immune and neuroendocrine systems].

There is an overwhelming evidence that cytokines, peptide hormones and neurotransmitters, as well as their receptors, are present in the brain, endocrine and immune systems. The structure and pattern of synthesis of these peptides by leukocytes appear similar to those synthesized in the neuroendocrine system, although some differences exist. Once secreted, these peptide hormones may function as endogenous regulators inside of the each system and also in bidirectional communication between the immune and neuroendocrine systems. Such communication suggest an immunoregulatory role for the brain and a sensory function for the immune system which may sense stimuli that are not recognized by the central and peripheral nervous systems (noncognitive stimuli). The plasma hormone concentrations contributed by lymphocytes usually do not reach the levels required when the pituitary gland is the source, but because immune cells are mobile, they have the potential to deposit the hormone locally at the target site. Several immunoregulatory cytokines, including IL-1, IL-2, IL-6, IFN-gama and TNF are produced not only in the immune system but in the neuroendocrine system as well. They have profound effects on neuroendocrine functions especially on hypothalamic pituitary axes. Neuroendocrine influences that modulate the immune function mainly include mental and physical stress. It can reduce the resistance of organism to infectious diseases and malignancies by compromising the immune system directly or indirectly. The brain is not an immunologically privileged site and therefore may become the target of immunologic attacks resulting in neuroimmunological diseases with an autoimmune component. The impact of psychological and psychosocial factors on the immune system is studied by psychoneuroimmunology whereas neuroendocrine immunology is generally interested in the interactions between the immune and neuroendocrine systems under physiological and pathological conditions. The recognition of the identity of ligands and receptors in the immune, nervous, and endocrine systems suggest a radically altered view of the immune systems impact on other tissues and organ systems, and vice versa. This will undoubtedly change our understanding of physiology, and consequently should profoundly impact the practice of medicine. (Tab. 5, Fig. 4, Ref. 85.)

Animals↗
PubMed1998

[Callus distraction for lengthening of mid-hand and finger stumps in congenital hand abnormalities--personal results and review of the literature].

Distraction-lengthening technique is quite useful in a variety of congenital hand deformities with hypoplastic, or primary normal but secondary shortened (constriction ring syndrome) finger rays. It appears that around the age of two years is the earliest practical time to start distraction; certainly distraction and secondary surgical procedures to improve function should be completed before school entry age whenever possible. Between June 1990 and March 1993, nine distraction lengthening procedures (5 thumbs, 1 index, 3 little fingers) in five patients presenting with congenital hand deformities, were carried out. Although restoring length to the finger, lengthening does not provide normal circumference or, of course, interphalangeal joint motion. Amelioration in function seems to be more important than the esthetic gain. Distraction lengthening tolerates only few errors of indication, operative technique, and/or postoperative management. A high compliance of the patient and her/his parents as well as a close follow-up by an experienced surgeon, are mandatory for a good result. A variety of possible complications have been described. Generally, complication risk increases in cases of simultaneous and multiple level lengthening. Provided adequate operative technique and postoperative care, superficial pin infection and fracture in the region of distraction are the major complications. Contrary to adults, sufficient bone formation by distraction is the rule in children. Therefore, the distraction-lengthening technique is preferred to the distraction-interposition technique in the treatment of congenital hand deformities. The latter should only be used as a salvage procedure in the rare cases of insufficient callus formation. Because of the missing growth potential and reduced joint mobility, distraction lengthening is the therapy of second choice when compared to microvascular second toe transplantation.

Acrocephalosyndactylia↗
PubMed2005

Clusters of mobile molecules in supercooled water.

We study the spatially heterogeneous dynamics in water via molecular dynamics simulations using the extended simple point charge potential. We identify clusters formed by mobile molecules and study their properties. We find that these clusters grow in size and become more compact as temperature decreases. We analyze the probability density function of cluster size, and we study the cluster correlation length. We find that clusters appear to be characterized by a fractal dimension consistent with that of lattice animals. We relate the cluster size and correlation length to the configurational entropy, S(conf). We find that these quantities depend weakly on 1/ S(conf). In particular, the linearity found between the cluster mass n(*) and 1/ S(conf) suggests that n(*) may be interpreted as the mass of the cooperatively rearranging regions that form the basis of the Adam-Gibbs approach to the dynamics of supercooled liquids. We study the motion of molecules within a cluster, and find that each molecule preferentially follows a neighboring molecule in the same cluster. Based on this finding we hypothesize that stringlike cooperative motion may be a general mechanism for molecular rearrangement of complex, as well as simple liquids. By mapping each equilibrium configuration onto its corresponding local potential energy minimum or inherent structure (IS), we are able to compare the mobile molecule clusters in the equilibrium system with the molecules forming the clusters identified in the transitions between IS. We find that (i) mobile molecule clusters obtained by comparing different system configurations and (ii) clusters obtained by comparing the corresponding IS are completely different for short time scales, but are the same on the longer time scales of diffusive motion.

Journal Article↗
PubMedDate not supplied

Morphine-potentiated platelet aggregation in in vitro and platelet plug formation in in vivo experiments.

The detailed mechanisms underlying morphine-signaling pathways in platelets remain obscure. Therefore, we systematically examined the influence of morphine on washed human platelets. In this study, washed human platelet suspensions were used for in vitro studies. Furthermore, platelet thrombus formation induced by irradiation of mesenteric venules with filtered light in mice pretreated with fluorescein sodium was used for an in vivo thrombotic study. Morphine concentration dependently (0.6, 1, and 5 microM) potentiated platelet aggregation and the ATP release reaction stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Yohimbine (0.1 microM), a specific alpha(2)-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by agonists. Morphine also potentiated phosphoinositide breakdown and intracellular Ca(2+) mobilization in human platelets stimulated by collagen (1 microg/ml). Moreover, morphine (0.6-5 microM) markedly inhibited prostaglandin E(1) (10 microM)-induced cyclic AMP formation in human platelets, while yohimbine (0.1 microM) significantly reversed the inhibition of cyclic AMP by morphine (0.6 and 1 microM) in this study. The thrombin-evoked increase in pH(i) was markedly potentiated in the presence of morphine (1 and 5 microM). Morphine (2 and 5 mg/g) significantly shortened the time require to induce platelet plug formation in mesenteric venules. We concluded that morphine may exert its potentiation in platelet aggregation by binding to alpha(2)-adrenoceptors in human platelets, with a resulting inhibition of adenylate cyclase, thereby reducing intracellular cyclic AMP formation followed by increased activation of phospholipase C and the Na(+)/H(+) exchanger. This leads to increased intracellular Ca(2+) mobilization, and finally potentiation of platelet aggregation and of the ATP release reaction.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2004

Understanding and designing field asymmetric waveform ion mobility spectrometry separations in gas mixtures.

Field asymmetric waveform ion mobility spectrometry (FAIMS) has significant potential for post-ionization separations in conjunction with MS analyses. FAIMS fractionates ion mixtures by exploiting the fact that ion mobilities in gases depend on the electric field in a manner specific to each ion. Nearly all previous work has used pure gases, for which FAIMS fundamentals are understood reasonably well; however, unexpected phenomena observed in some gas mixtures (e.g., N(2)/CO(2)) but not in others (N(2)/O(2)) remain unexplained. Here, we introduce and experimentally test a universal model for FAIMS separations in mixtures, derived from formalisms that determine high-field mobilities in heteromolecular gases. Overall, the theoretical findings are consistent with data for N(2)/CO(2) (although quantitative discrepancies remain), while results for N(2)/O(2) fit Blanc's law, in agreement with measurements. Calculations for He/N(2) and He/CO(2) are also consistent with observations and suggest why adding He to the working gas generally enhances FAIMS performance. As predicted, mixtures of gases with extremely disparate molecular masses and collision cross sections, such as He/SF(6), exhibit spectacular non-Blanc effects, which greatly improve the resolution and peak capacity of technique. Understanding FAIMS operation in gas mixtures is expected to enable the rational design of media for both targeted and global analyses.

Carbon Dioxide↗
PubMedDate not supplied

Endothelin receptor regulation by endothelin synthesis in vascular smooth muscle cells: effects of dexamethasone and phosphoramidon.

One of the major biological effects of the endothelium-derived peptide endothelin-1 (ET-1) is its receptor-mediated constrictive action on vascular smooth muscle. In this study, we have examined the effects on the ET-1 pathway of 18 h exposure at 37 degrees C of cultured rat aortic smooth muscle cells to dexamethasone (DEX) and phosphoramidon. ET-1 synthesis was evaluated by radioimmunoassay, ET-1 binding characteristics were determined with [125I]iodo-ET-1, and ET-1-induced intracellular calcium mobilization was measured using fura-2-loaded cells. DEX (100 nM) led to a 2- to 3-fold-increase of ET-1 production, it down-regulated ET-1 receptors and reduced ET-1-stimulated calcium mobilization by 70%. In contrast, phosphoramidon (100 microM) inhibited ET-1 production by 60%, up-regulated ET-1 receptors and potentiated ET-1-induced calcium mobilization by 75%. These results indicate that the regulatory effects of DEX and phosphoramidon on ET-1 receptors are mediated via ET-1 production by the cells. This suggests an autocrine control of ET-1 receptors by endogenous ET-1 synthesis in vascular smooth muscle cells.

Animals↗
PubMed1992

Quantitative measurement of lipoprotein surface charge by agarose gel electrophoresis.

The electrophoretic mobilities of low density lipoprotein (LDL) and six pure proteins in a 0.5% agarose gel have been compared to literature electrophoretic mobility values determined by the Tiselius moving boundary method. There is a strong correlation (r = 0.99) between the electrophoretic mobilities determined by the two techniques. The electrophoretic behavior of charged particles smaller than very low density lipoproteins (VLDL) is not markedly perturbed by a 0.5% agarose matrix, and variations in mobility primarily reflect differences in particle valence and density of surface charge. Application of electrokinetic theory to derive protein and lipoprotein net charges from the electrophoretic mobilities in agarose yields a quantitative delineation of lipoprotein electrophoretic migration patterns wherein the beta mobility region comprises a surface potential range of -4.5 to -7.0 mV; the pre-beta region a range of -7.0 to -10.5 mV; the alpha mobility region a range of -10.5 to -12.5 mV and the serum albumin region a range of -12.5 to -14.0 mV. Because protein conformation and charge are critical in metabolic regulation, the agarose gel electrophoresis technique provides a valuable analytical tool that should help to elucidate further details of the structure-function relationships of serum lipoprotein particles.

Electrochemistry↗
PubMed2001

Influence of mobile phones on accuracy of ECG interpretation algorithm in automated external defibrillator.

BACKGROUND: Automated External Defibrillators (AED) are a recommended tool for out-of-hospital emergency medical services. Mobile phones (GSM) are a potential source of electromagnetic interference which may cause failure of ECG interpretation and subsequent inappropriate action of AED's. METHODS: We evaluated the influence of 900 MHz GSM phones on the accuracy of automatic ECG interpretation with a GSM Mobile Station Tester with adjustable power and mode of transmission (Hewlett-Packard HP5515A), GSM phones (Alcatel, Ericsson, Nokia, Panasonic), ECG simulator (Metron) and four AEDs (Fore Runner-Hewlett-Packard, Heartstart 3000-Laerdal, Cardio-Aid 100-Artema, Heartstream XLT-Agilent). The protocol included 18 different ECG patterns, different ECG voltages, and different power and mode of transmission. RESULTS: The first stage of the protocol included minimal power of signal transmitted from GSM Mobile Station Tester and maximum power of GSM phone's signal--hence maximal potential interference to AED. The protocol was based on close direct contact between the GSM phone and the AED device. Regardless of the ECG pattern, with both 0.5 and 1.0 mV ECG voltage, and the GSM phone placed on various parts of AED device or at the patient cable, no failure of AED algorithm occurred. No detectable noise was seen at AED's ECG display. CONCLUSION: AEDs seems to be well protected against clinically significant failure caused by noise from 900 MHz GSM phones.

Electric Countershock↗
PubMed1991

Ethanol causes desensitization of receptor-mediated phospholipase C activation in isolated hepatocytes.

The effect of ethanol on receptor-mediated phospholipase C-linked signal transduction processes was investigated in isolated rat hepatocytes. Pretreatment of the cells with ethanol (6-300 mM) markedly inhibited a subsequent stimulation of phospholipase C by vasopressin, angiotensin II, or epidermal growth factor. By contrast, the effects of the alpha 1-adrenergic agonist phenylephrine and of glucagon were not affected by ethanol pretreatment. Ethanol inhibited the agonist-induced decrease in polyphosphoinositides, the formation of inositol phosphates, and the increase in cytosolic free Ca2+ levels, as detected with the intracellular Ca2+ indicator indo-1. The effects of ethanol were concentration dependent and were pronounced at low concentrations of agonists but were not significant at saturating levels. Pretreatment of the cells with the protein kinase C inhibitor H7 partly prevented the inhibition by ethanol of vasopressin-induced phospholipase C activation. By contrast, pretreatment of the cells with (Rp)-adenosine cyclic 3':5'-phosphorothioate [Rp)-cAMP-S), a competitive inhibitor of protein kinase A, potentiated the inhibitory effect of ethanol on the Ca2+ mobilization by vasopressin. (Rp)-cAMP-S similarly potentiated the inhibition of phospholipase C by the protein kinase C-activating phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). The kinase A inhibitor also made the Ca2+ mobilization by phenylephrine sensitive to ethanol, indicating that the formation of cAMP in the cells played a role in suppressing the sensitivity to ethanol. Pretreatment of the cells with ethanol enhanced the inhibitory effects of TPA on the vasopressin-induced phospholipase C activation at all concentrations of the hormone; however, these synergistic effects were prevented when TPA was added prior to ethanol, a condition that prevents the activation of phospholipase C by ethanol. The data indicate that ethanol causes desensitization of the receptor-mediated phospholipase C secondary to the ethanol-induced activation of phospholipase C and activation of protein kinase C. Ethanol treatment also affects the sensitivity of the phospholipase C system to control by protein kinases A and C. The data indicate that ethanol can affect the control of intracellular signal transduction processes in liver cells under physiologically relevant conditions.

Angiotensin II↗
PubMed2001

Progenipoietin-1: a multifunctional agonist of the granulocyte colony-stimulating factor receptor and fetal liver tyrosine kinase-3 is a potent mobilizer of hematopoietic stem cells.

OBJECTIVE: Progenipoietin-1 is an agonist of both the granulocyte colony-stimulating factor and fetal liver tyrosine kinase-3 receptors capable of inducing the proliferation of multiple hematopoietic cell lineages. The potential of progenipoietin-1 to mobilize transplantable hematopoietic stem cells into the peripheral blood was evaluated. METHODS: Cohorts of donor mice were treated with either progenipoietin-1, fetal liver tyrosine kinase-3 ligand, granulocyte colony-stimulating factor, or a vehicle control. Hematopoietic progenitor/stem-cell activity in donor blood was assayed by radioprotection, multilineage reconstitution, secondary transplantation, and competitive repopulation. RESULTS: Only 1 microL of peripheral blood from progenipoietin-1-treated donors was required to protect 80% of lethally irradiated mice, while in contrast 1 microL of peripheral blood from granulocyte colony-stimulating factor-treated donors failed to protect any recipients. The radioprotected recipients of progenipoietin-1-treated donor cells showed donor-derived (Ly5.2) multilineage hematopoietic reconstitution for up to 6 months. Serial transplantation studies using bone marrow from radioprotected, chimeric recipients demonstrated long-term donor-derived hematopoiesis, indicating the successful transplantation of multipotent hematopoietic stem cells. The engraftment potential of progenipoietin-1 donor-derived cells was directly compared with donors treated with granulocyte colony-stimulating factor or fetal liver tyrosine kinase-3 ligand alone or in combination. Both spleen colony-forming activity and competitive repopulating activity was highest in the blood from progenipoietin-1-treated donors. CONCLUSIONS: These studies demonstrate that progenipoietin-1 is a potent mobilizer of transplantable hematopoietic stem cells and indicate that this dual-receptor agonist has greater biologic activity than its constituent molecules.

Animals↗
PubMed1994

Interactions between adenosine A1- and histamine H1-receptors.

The interactions or "cross-talk" between adenosine A1-receptors and receptors coupled to phospholipase C (leading to the hydrolysis of inositol phospholipids) have been well documented in the literature. For example, activating the A1-receptor selectively potentiates the histamine H1-receptor stimulated hydrolysis of inositol phospholipids in guinea-pig cerebral slices. In contrast, when the adenosine receptor is activated in the cerebral cortex of mouse or man the histamine response is selectively inhibited. Our studies have focused on the smooth muscle cell line, DDT1 MF-2, derived from hamster vas deferens. These cells express A1-receptors which, in addition to the expected negative coupling to adenylate cyclase, also stimulate inositol phospholipid hydrolysis and Ca2+ mobilization. These A1-receptors also potentiate histamine H1-receptor responses, i.e. inositol phospholipid hydrolysis and Ca2+ mobilization. The mechanism(s) underlying the potentiation or inhibition of histamine H1-receptor responses by the adenosine A1-receptor remain to be unravelled. One mechanism may involve intracellular "cross-talk" at the G-protein level. This review will discuss how beta gamma subunits from G(i) proteins could be involved in augmenting responses to calcium mobilizing receptors.

Animals↗
PubMed1997

Induction of interleukin-12 p40 transcript by CD40 ligation via activation of nuclear factor-kappaB.

Interleukin-12 is produced in response to infection with bacteria or parasites or to bacterial constituents such as LPS in monocytes/macrophages and dendritic cells, and also generated by the interaction between activated T cells and antigen-presenting cells via CD40-CD40 ligand (CD40L). So far, transcriptional analyses of p40 have been carried out only using bacterial constituents such as LPS as stimuli. In the present study, we have characterized the transcriptional induction of p40 by CD40 ligation in a human B lymphoblastoid cell line, Daudi, and a human acute monocytic leukemia cell line, THP-1. These cells, stimulated by an agonistic monoclonal antibody against CD40 or by transfection with a CD40L expression vector, secreted p40 and showed enhanced p40 mRNA expression. Sequence analysis of the p40 promoter region identified two potential nuclear factor (NF)-kappaB binding sites conserved between mouse and human. Electrophoretic mobility shift assay revealed that the potential NF-kappaB binding sequence which is located around 120 bp upstream of the transcription initiation site in murine and human p40 genes formed an NF-kappaB complex with nuclear extract from Daudi cells stimulated by CD40 ligation. Moreover, transfection of Daudi cells with the polymerized NF-kappaB binding sequence ligated to a thymidine kinase/chloramphenicol acetyltransferase (CAT) reporter plasmid greatly induced CAT activity, but transfection with the polymerized mutated NF-kappaB binding sequence did not. These results suggest that the NF-kappaB binding site located around 120 bp upstream of the transcription initiation site in murine and human p40 promoter regions could be important for the p40 induction by CD40 ligation via activation of NF-kappaB.

Animals↗
PubMed1994

Evidence for participation of calcineurin in potentiation of agonist-stimulated cyclic AMP formation by the calcium-mobilizing hormone, angiotensin II.

Angiotensin II (AII) receptors are known to interact with two distinct guanine nucleotide binding proteins, Gq/11 and Gi, in rat adrenal glomerulosa cells to activate phospholipase C and to inhibit adenylate cyclase, respectively. However, in cultured bovine glomerulosa cells AII potentiates rather than inhibits the stimulatory effect of adrenocorticotropin (ACTH) on cAMP levels. This effect of AII was partially mimicked by phorbol 12-myristate 13-acetate (PMA) and was partially inhibited by staurosporine or depletion of protein kinase C but was unaffected by pertussis toxin treatment. No potentiation was detectable in disrupted cells or in membrane preparations. In intact glomerulosa cells, treatment with cyclosporin A or FK506 completely inhibited AII- or PMA-induced potentiation of cAMP production without affecting the response to ACTH. In COS-7 cells transfected with the rat AT1 receptor, AII caused 2-3-fold enhancement of the ACTH-induced cAMP response, an effect that was partially reproduced by PMA. These potentiating actions of AII and PMA were prevented by preincubation with cyclosporin A or FK506, and the latter effect was abolished by rapamycin. These results implicate the Ca2+- and calmodulin-dependent protein phosphatase, calcineurin, in AII-induced enhancement of adenylate cyclase activity in both adrenal glomerulosa and transfected COS-7 cells. The finding that AII enhances ACTH-stimulated production of cAMP by a second messenger-mediated mechanism that involves the participation of calcineurin reveals an additional mode of cross-talk between pathways activated by Ca(2+)-mobilizing and cAMP-generating receptors.

Adrenocorticotropic Hormone↗
PubMed2000

Detection of circulating tumor cells by reverse transcriptase polymerase chain reaction of maspin in patients with breast cancer undergoing conventional-dose chemotherapy.

PURPOSE: To establish, in patients with breast cancer subjected to primary conventional chemotherapy and enrolled in a prospective study, the mobilizing effect of therapy on potentially neoplastic cells by means of a reverse transcriptase polymerase chain reaction (RT-PCR) assay for mRNA of maspin, a protein related to the serpin family of protease inhibitors. PATIENTS AND METHODS: Peripheral-blood samples were collected from 30 patients with histologically proven breast cancer before and 4 and 8 days after conventional chemotherapy for three consecutive courses. A total of 216 samples were screened for the presence of maspin mRNA by RT-PCR. RESULTS: Before therapy, all samples but one were negative. After chemotherapy, 11 patients (38%) had positive samples. No difference in the rate of positivity was observed between groups defined according to initial stage, type of chemotherapy, Ki-67-related proliferative activity, or CA 15.3 expression. CONCLUSION: Our results confirm that RT-PCR for maspin mRNA is a sensitive assay for the study of circulating potentially neoplastic mammary cells in patients with breast cancer. Moreover, our findings indicate a marked effect of conventional-dose chemotherapy on the mobilization of these cells in breast tumors. In our series of patients, this phenomenon does not seem to be associated with other known risk factors. Finally, the data suggest, without proving, an association between the presence of circulating maspin positive cells and a higher risk of disease progression. If this association could be confirmed, then the assay could have prognostic significance. However, larger confirmatory studies are necessary.

Adult↗