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Biomedical subjects

C Song

Publications and source records attributed to C Song.

At least 37 records · Page 2Linked to original sources
PubMed2000

Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist.

In schizophrenic patients, multiple immune abnormalities have been reported, including increased production of proinflammatory cytokines. There is some evidence that antipsychotic drugs may have immunosuppressive effects. The aim of this study was to examine the in-vitro effects of different concentrations of antipsychotic agents on cytokine production by human whole blood. We examined the effects of clozapine and haloperidol, 10(-4), 10(-6) and 10(-8)M, on the unstimulated and stimulated (lipopolysaccharide+phytohemagglutinin) production of interleukin-6 (IL-6), IL-10, interferon-gamma (IFNgamma), and the IL-1 receptor antagonist (IL-1RA). Clozapine, 10(-6) and 10(-8)M, and haloperidol, 10(-4), 10(-6), and 10(-8)M, significantly increased the unstimulated and stimulated production of IL-1RA. Clozapine 10(-6)M significantly increased the stimulated production of IFNgamma. Clozapine 10(-4)M significantly suppressed the unstimulated production of IL-6 and IL-1RA and the stimulated production of IL-6, IL-10, IFNgamma and IL-1RA. The results suggest that both clozapine and haloperidol, at concentrations within the therapeutic range, may exert immunosuppressive effects through an enhanced production of IL-1RA.

Adult↗
PubMed2000

A transcriptional defect underlies B lymphocyte dysfunction in a patient diagnosed with non-X-linked hyper-IgM syndrome.

To establish the underlying cause of hyper-IgM syndrome in one female patient, B cell function was examined in response to CD40- and IL-4-mediated pathways. When CD40-induced functional responses were measured in unfractionated B cells, CD80 up-regulation, de novo Cmu-Cgamma recombination, and Igamma transcription were all found to be relatively unaffected. However, CD40- and IL-4-mediated CD23 up-regulation and VDJ-Cgamma transcription were clearly diminished compared to control cells. IL-4-induced CD23 expression was measurably reduced in the CD20- population as well. These results suggested that the patient's defect is positioned downstream of CD40 contact and affects both CD40- and IL-4 signal transduction pathways. Further analysis of B cell function in CD19+ B cells revealed a clear B cell defect with respect to Igamma and mature VDJ-Cgamma transcription and IgG expression. However, under the same conditions Iepsilon transcription was relatively normal. Partial restoration of B cell function occurred if PBMC or CD19+ B cells were cultured in vitro in the presence of CD154 plus IL-4. Because addition of IL-4 to cocultures containing activated T cells failed to induce B cells to undergo differentiation, the ability of the patient's B cells to acquire a responsive phenotype correlated with receiving a sustained signal through CD40. These findings support a model in which the patient expresses an intrinsic defect that is manifested in the failure of specific genes to become transcriptionally active in response to either CD154 or IL-4 and results in a functionally unresponsive B cell phenotype.

B-Lymphocytes↗
PubMed2000

Superoxide possibly produced in endothelial cells mediates the neutrophil-induced lung injury.

BACKGROUND: The mechanism by which stimulated neutrophils (polymorphonuclear leukocytes [PMNs]) damage pulmonary vascular endothelium was investigated. METHODS: The ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability was tested. Each series was conducted on 6 rats. To stimulate PMNs, they were agitated gently in a glass vial for 10 seconds. RESULTS: Perfusing lungs with the stimulated PMNs elicited a fivefold increase in permeability compared with lungs perfused with the unstimulated cells. This increase in permeability was blocked completely by preincubation of stimulated PMNs with CD18 monoclonal antibody. This increase in permeability was also blocked completely by superoxide dismutase (SOD) or the xanthine oxidase (XO) inhibitor allopurinol. Pulmonary vascular hemodynamics were unaffected by any treatment protocol. The accumulation of stimulated PMNs within the lungs was not inhibited by SOD but was partially blocked by allopurinol. CONCLUSIONS: These findings suggest that stimulated PMN-induced increases in pulmonary vascular filtration resulted from endothelial cell injury caused by superoxide anion possibly generated by XO, exclusively present in the endothelial cells.

Animals↗
PubMed2000

Selective activation of liver X receptor alpha by 6alpha-hydroxy bile acids and analogs.

We have found that certain natural 6alpha-hydroxylated bile acids are receptor-specific activators of nuclear liver X receptor alpha (LXRalpha) (NR1H3), a nuclear receptor regulating the expression of the cholesterol 7alpha-hydroxylase gene, coding for the rate-limiting enzyme in the major pathway of bile acid synthesis. The LXR homolog, ubiquitous nuclear receptor (UR/LXRbeta) (NR1H2), was also activated by these bile acids, but at higher concentrations than for LXRalpha. Synthetic 6alpha-hydroxylated bile acid analogs were synthesized with LXRalpha-selective agonistic activity, with potential to modulate cholesterol catabolism in hypercholesterolemia.

Bile Acids and Salts↗
PubMed2000

The in vitro immunosuppressive effects of moclobemide in healthy volunteers.

BACKGROUND: Many studies have demonstrated that major depression is related to an activation of the inflammatory response system (IRS) with an increased production of proinflammatory cytokines. It has been shown that tricyclic antidepressants and serotonin reuptake inhibitors suppress the activation of the IRS in depression and have negative immunoregulatory effects in vitro. Little is known on the immune effects of moclobemide, a reversible monoamine oxidase A inhibitor. METHODS: We examined, in nine normal volunteers, the in vitro effects of moclobemide on the production of interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), IL-10 and the IL-1 receptor antagonist (IL-1RA) by diluted whole blood stimulated or not with lipopolysaccharide (LPS)+phytohemagglutinin (PHA). RESULTS: Moclobemide 10(-3) and 10(-5) M significantly suppressed the unstimulated production of TNFalpha and IL-8, and significantly enhanced the stimulated-production of IL-10. The production of IL-6, IL-1RA and IFNgamma was not significantly affected either in the unstimulated or stimulated conditions. CONCLUSIONS: Moclobemide has negative immunoregulatory capacities through inhibition of the production of proinflammatory cytokines, i.e. TNFalpha and IL-8, and through enhancement of the production of IL-10, an anti-inflammatory cytokine.

Adult↗
PubMed2000

Endothelial signal transduction system enhances neutrophil-induced pulmonary vascular permeability.

The mechanism by which stimulated polymorphonuclear leukocytes and neutrophils (PMNs) damage pulmonary vascular endothelium was investigated. The authors assessed the ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability, measured as the pulmonary filtration coefficient (K) and haemodynamics. PMNs were stimulated by gentle agitation in a glass vial for 10 s. Perfusing lungs with the stimulated PMNs (n=6) resulted in significant accumulation of PMNs within the lungs, assessed by myeloperoxidase levels, and elicited a 4-fold increase in K and a 2-fold increase in pulmonary vascular resistance as compared to lungs perfused with unstimulated cells (n=6). The increases in K were completely blocked by GF109203X, a protein kinase C inhibitor (n=6); however, GF109203X only partially attenuated the increase in vascular resistance and had little effect on the accumulation of stimulated PMNs. An agonist of protein kinase C, phorbol myristate acetate, elicited dose dependent increases in both K and pulmonary vascular resistance even in the absence of PMNs (n=6). These findings indicate that the increases in pulmonary filtration coefficient and pulmonary vascular resistance induced by polymorphonuclear neutrophils result from endothelial cell injury mediated by activation of protein kinase C within the endothelial cells themselves.

Animals↗
PubMed2000

A polymorphic CD40 ligand (CD154) molecule mediates CD40-dependent signalling but interferes with the ability of soluble CD40 to functionally block CD154:CD40 interactions.

We report the characterization of a naturally occurring polymorphism in CD40 ligand (CD40L, CD154) expressed by activated T cells from a young female patient. This polymorphism encodes a nonconservative Gly --> Arg substitution in amino acid 219 in the extracellular, CD40 binding domain of the molecule. Studies carried out with 293 epithelial cells ectopically expressing the polymorphic protein (CD154/G219R) revealed reduced levels of binding to different anti-CD154 monoclonal antibodies (mAb) and CD40-immunoglobulin (CD40-Ig). However, recognition of the polymorphic and wild-type CD154 molecules by a polyclonal antiserum was comparable, suggesting that the polymorphism affects the ability of the protein to interact with CD40 but does not significantly alter its surface expression. To determine if reduced cross-linking of CD40 mediated decreased functional effects, three CD40-dependent properties were measured. We found that pathways leading to the induction of surface CD23, CD80, and Igamma transcription were activated in response to CD154/G219R signalling. However, the decrease in affinity for CD40 by the mutated CD154 affected the ability of CD40-Ig to efficiently interfere with the binding and effectively block induced CD80 expression. In contrast, we found that the 5c8 mAb, which recognized the polymorphic molecule to a similar extent as wild-type CD154, effectively blocked the interaction between CD154/G219R and CD40 as measured by CD80 expression. These findings suggest that naturally occurring polymorphisms in the CD154 molecule may affect the ability of CD40-mediated functions to be blocked by soluble CD40 or anti-CD154 mAb in the therapeutic treatment of disease and graft rejection.

B7-1 Antigen↗
PubMed2000

Difference in the effects of low temperatures on the tension of human pulmonary artery and vein ring segments.

BACKGROUND: Although limited data suggest that pulmonary flushing with organ preservation solutions should not be performed at too low temperatures, the influence of temperature on pulmonary vascular tone is unclear. OBJECTIVE: The purpose of this study was to examine the effect of low temperatures of the tension of human pulmonary artery and vein ring segments and the vascular resistance of perfused rat lungs. METHODS: 5 sets of human pulmonary artery and vein ring segments were suspended from a force displacement transducer at 37, 24 and 8 degrees C, and the effect of 30 mM K(+) on the tension was monitored. The effect of 30 mM K(+) on vascular resistance was also examined at low temperatures in 5 perfused rat lungs. RESULTS: Pulmonary artery segments dilated at 24 degrees C, and more significant vasodilatation was observed at 8 degrees C. In contrast, there was a significant constriction of pulmonary veins at 8 degrees C. Vasoconstriction induced by 30 mM K(+) at 37 degrees C was significantly inhibited at low temperatures in both pulmonary arteries and veins. In rat lungs, perfusion at 8 degrees C caused a significant increase in pulmonary vascular resistance, even though no further increase was observed in the presence of 30 mM K(+). CONCLUSIONS: Our data indicate that pulmonary arteries dilate and the veins constrict at 8 degrees C and may increase pulmonary vascular resistance. We conclude that the different effect of low temperatures between pulmonary arteries and veins may explain why pulmonary vascular flushing with organ preservation solutions at room temperature is more satisfactory.

Adult↗
PubMed2000

Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha.

Excessive cholesterol is eliminated from extrahepatic cells by reverse cholesterol transport, a process by which neutral sterols are transferred to extracellular acceptor lipoproteins for further transport to the liver. Another process independent of lipoproteins involves excretion of 3beta-hydroxy-5-cholesten-25(R)-26-carboxylic (cholestenoic) acid, a metabolite of 27-hydroxycholesterol. Physiological concentrations of cholestenoic acid activated the nuclear receptor liver X receptor alpha (LXR alpha; NR1H3), but not other oxysterol receptors. As a ligand, cholestenoic acid modulated interaction of LXR alpha with the nuclear receptor coactivator Grip-1. Cholestenoic acid, therefore, may function as a signaling molecule for regulation of lipid metabolism via LXR alpha.

Cell Line↗
PubMed2000

[The in vivo degradation, adsorption and excretion of poly(epsilon-caprolactone)].

The in vivo degradation of poly(epsilon-caprolactone(PCL) was studied in rats. The results showed that the PCL capsules with an initial molecualr weight of 66,000 stayed intact in vivo for 2 years, although the molecular weight of the capsules gradually declined during the two-year implantation. It then degraded into low molecular wight pieces with the extension of the implantation. Tritium-labeled low molecular weight PCL was subcutaneously implanted in rats to further investigate the absorption and excretion of the material. The radioactivity was first detected in blood 15 days post the implantation. At the same time radioactive excreta were recovered from feces and urine. An accumulative 92% of the implanted radioactive dosage was excreted from feces and urine 135 days post the implantation. In the meanwhile, the blood radioactivity dropped to the background level. Radioactivity in the organs was all close to the background level indicating that the material did not cumulate in body tissue and could be completely excreted.

Absorption↗
PubMed1999

Molecular characterization of cytosolic phospholipase A2-beta.

We have isolated a cDNA encoding a 1012-amino acid polypeptide cPLA2-beta, that has significant homology with cPLA2-alpha in both the calcium-dependent lipid binding domain as well as in the catalytic domain. Transient expression of cPLA2-beta cDNA in COS cells results in an increase in calcium-dependent phospholipase A1 (PLA1) and PLA2 activities compared with vector-transfected cells. cPLA2-beta is markedly less selective for cleavage at sn-2 as compared with cPLA2-alpha and cPLA2-gamma. Northern analysis reveals a cPLA2-beta transcript of 8 kilobase pairs that is expressed in all the human tissues examined. With the identification of cPLA2-beta, the newly defined cPLA2 family now comprises three members that may have dramatically different mechanisms for regulation of expression and enzymatic activation.

Amino Acid Sequence↗
PubMed1999

Cytokines in detoxified patients with chronic alcoholism without liver disease: increased monocytic cytokine production.

BACKGROUND: The aim of the present study was to examine the production of interferon-gamma, tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-6 (IL-6), IL-10, IL-4, IL-5, IL-1 receptor antagonist (IL-1RA), and prostaglandin E2 in relation to the number of leukocytes in the blood of detoxified, chronic alcoholic patients without apparent liver disease (AWLD). METHODS: Phytohemagglutinin + lipopolysaccharide-induced production of the above variables as well as the number of white blood cells and differentials were determined in detoxified AWLD patients and normal volunteers. RESULTS: Detoxified AWLD patients have a significantly higher production of IL-6, IL-10, TNF-alpha, GM-CSF, and IL-1RA and significantly increased numbers of leukocytes and neutrophils compared to normal volunteers. CONCLUSIONS: Detoxified AWLD patients show an increased production of proinflammatory cytokines, i.e., IL-6, TNF-alpha, and GM-CSF, as well as negative immunoregulatory proteins, such as IL-10 and IL-1RA.

Adult↗
PubMed1999

Influence of psychological stress on immune-inflammatory variables in normal humans. Part II. Altered serum concentrations of natural anti-inflammatory agents and soluble membrane antigens of monocytes and T lymphocytes.

The effects of academic examination stress on serum concentrations of interleukin (IL)-1 receptor (R) antagonist (A), soluble(s) IL-2R, sIL-6R, soluble glycoprotein 130 (sgp130), Clara cell protein (CC16), sCD8 and sCD14 were evaluated in 38 university students. The relationships among changes in the above immune-inflammatory variables, levels of serum cortisol, and scores on the Perceived Stress Scale (PSS) or the State-Trait Anxiety Inventory (STAI) were examined. Academic examination stress was associated with significant increases in PSS and STAI scores, and in serum sgp130 and sCD8 values. Academic examination stress was associated with significantly decreased serum sCD14 concentrations in students with high, but not low, stress perception. There were stress-induced differences in serum IL-1RA, sIL-6R and CC16 concentrations between students with high vs. low stress-induced anxiety. The stress-induced increase in serum sCD8 was significantly more pronounced in male students, whereas the increase in serum sgp130 was more pronounced in female students taking contraceptive drugs. These results suggest that: (1) psychological stress induces immune-inflammatory changes pointing toward complex regulatory responses in IL-6 signalling, a decreased anti-inflammatory capacity of the serum, and interactions with T cell and monocytic activation; and that (2) sex hormones may modify stress-induced immune-inflammatory responses.

Adaptation, Psychological↗
PubMed1999

Stressor-induced alterations in serotonergic activity in an animal model of depression.

The present study examined the effect of two neurogenic stressors (air puff and restraint) and a metabolic stressor (lipopolysaccharide; LPS 100 microg/kg, i.p.) on accumbal serotonergic neurotransmission in the olfactory bulbectomized (OB) rat model of depression. Both air puff and restraint stress caused greater increases in accumbal 5-HIAA in OB than in sham-operated rats. In contrast, bulbectomy resulted in a blunted serotonergic response to a challenge with LPS (a metabolic stressor). In addition, OB rats displayed significantly lower basal levels of 5-HIAA than sham-operated counterparts, a finding consistent with previous reports of the OB rat being a model of hyposerotonergic depression. The relevance of these findings to stressor-provoked depressive-like behaviors in the OB rat are discussed.

Air↗
PubMed1999

Alterations in immune functions during normal aging and Alzheimer's disease.

It is thought that aging induces immune changes, which are related to the pathophysiology of Alzheimer's disease (DAT). In this study, the total number of leukocytes, white blood cell differentiation, mitogen-induced lymphocytic proliferation, neutrophil phagocytosis and superoxide release, and prostaglandin E2 (PGE2) production by mitogen-stimulated whole blood cultures were comparatively investigated between healthy adults (range 22-45 years) and healthy elderly volunteers (range 70-91 years), and between DAT patients (range 56-94 years) and age-matched control subjects. Healthy elderly volunteers showed significantly lower phytohemagglutinin (PHA)-induced lymphocyte proliferation and percentage and absolute number of basophils than young volunteers. In normal volunteers, there were significant and negative correlations between age and the number of basophils. Patients with DAT showed a trend toward significantly higher PHA-induced lymphocyte proliferation and significantly decreased percentage and absolute number of large unstained cells than healthy volunteers. In DAT patients, the total number of leukocytes and the percentage and number of neutrophils were positively correlated with age. All other immune-inflammatory variables were not significantly altered either by the aging process or DAT. The present study suggests that aging and DAT may differently affect some immune variables.

Adult↗
PubMed1999

Effect of phosphorylation on activities of Rap1A to interact with Raf-1 and to suppress Ras-dependent Raf-1 activation.

Rap1A is phosphorylated by cAMP-dependent protein kinase (PKA), and this phosphorylation has been shown to modulate its interaction with other proteins. However, it is not known whether Rap1A phosphorylation is involved in regulation of its cellular functions, including suppression of Ras-dependent Raf-1 activation. We have previously shown that this suppressive activity of Rap1A is attributable to its greatly enhanced ability to bind to the cysteine-rich region (CRR, residues 152-184) of Raf-1 compared with that of Ras. Here, we show that phosphorylation of Rap1A by PKA abolished its binding activity to CRR. Furthermore, a mutant Rap1A(S180E), whose sole PKA phosphorylation residue, Ser-180, was substituted by an acidic residue, Glu, to mimic its phosphorylated form, failed to suppress Ras-dependent Raf-1 activation in COS-7 cells. These results indicate that the CRR binding activity and the Ras-suppressive function of Rap1A can be modulated through phosphorylation and suggest that Rap1A may function as a PKA-dependent regulator of Raf-1 activation, not merely as a suppressor.

Amino Acid Sequence↗