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Biomedical subjects

C Song

Publications and source records attributed to C Song.

At least 55 records · Page 3Linked to original sources

[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↗

[Allotransplantation of cultured fetal parathyroid gland cells in treating patients with hypoparathyroidism].

OBJECTIVE: To evaluate the therapeutic efficacy of transplantation of cultured human fetal parathyroid gland (chf-PTG) cells in treating patients with primary or secondary hypoparathyroidism. METHODS: Chf-PTG cells were allotransplanted into the renal adipose capsules of 6 patients with hypoparathyroidism under the ultrasonic guidance. The levels of serum parathyroid hormone (PTH) and calcium were monitored by radioimmunometric assay (RIA) and biochemical method, respectively. Both indexes of pre-and post-operation were compared and the data were analyzed. RESULTS: The levels of serum PTH and calcium were markedly elevated from three days to the first two weeks following transplantation of chf-PTG cells (P < 0.01). The PTH and calcium levels gradually stabilized from day 14 up to months 9-12, during which the symptoms of the patients alleviated or relieved. CONCLUSION: The transplantation of chf-PTG cells is a potential method for treating patients with primary or secondary hypoparathyroidism.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

Superoxide anion mediates pulmonary vascular permeability caused by neutrophils in cardiopulmonary bypass.

During cardiopulmonary bypass (CPB), neutrophils (PMNs) may be stimulated by shear stress which could contribute to the pulmonary injury that occurs after CPB. To elucidate whether mechanically stimulated PMNs increase pulmonary vascular permeability, measured as the pulmonary filtration coefficient (K) and pulmonary vascular resistance, and to elucidate whether superoxide anion mediates this increase, we assessed the effects of stimulated and unstimulated PMNs, and of superoxide dismutase (SOD) on K and resistance in isolated perfused lungs from Sprague-Dawley rats. PMNs were stimulated by gentle agitation in a glass vial for 10 s. Lungs perfused with the stimulated PMNs, being the stimulated group (n = 6), elicited a 5-fold increase in the filtration coefficient compared with lungs perfused with unstimulated cells, being the unstimulated group (n = 6). This increase in filtration was completely blocked by the preincubation of stimulated PMNs with CD18 monoclonal antibody, being the Ab group (n = 6), and also by superoxide dismutase, being the SOD group (n = 6). Pulmonary vascular resistance was not increased by stimulated PMNs, and the accumulation of stimulated PMNs was not blocked by SOD. These findings suggest that stimulated PMNs increase K and that superoxide anion may injure the pulmonary vascular endothelial cells.

Analysis of Variance↗

In vitro immunoregulatory effects of lithium in healthy volunteers.

RATIONALE: There is now some evidence that major depression is associated with activation of the inflammatory response system (IRS). Lithium is effective in the treatment and prophylaxis of major depression and shows significant immunoregulatory functions. OBJECTIVE: The aims of the present study were to examine the in vitro effects of lithium on the unstimulated and lipolysaccharide (LPS) + phytohemagglutinin (PHA)-induced production of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma), and negative immunoregulatory cytokines or proteins, such as IL-10 and the IL-1 receptor antagonist (IL-1RA). METHODS: The in vitro effects of lithium carbonate at low (10(-4) M and 10(-5) M) and therapeutic (10(-3) M) concentrations on the above cytokines and the IL-1RA were examined in nine healthy volunteers on whole blood supernatant cultured for 72 h. RESULTS: Lithium (10(-3) M) in the presence of LPS+PHA significantly increased the stimulated production of IFNgamma, IL-8, TNFalpha, IL-1RA and IL-10. Lithium (10(-3) M) significantly increased the unstimulated production of IL-8 and IL-10. CONCLUSIONS: The results suggest that lithium has significant immunoregulatory effects by increasing the production of both proinflammatory cytokines (IFNgamma, TNFalpha and IL-8) and negative immunoregulatory cytokines or proteins (IL-10 and the IL-1RA).

Adjuvants, Immunologic↗

Variations of nucleus accumbens dopamine and serotonin following systemic interleukin-1, interleukin-2 or interleukin-6 treatment.

The effects of systemically administered interleukin-1beta (1.0 microg), interleukin-6 (1.0 microg) and interleukin-2 (1.0 microg) on in vivo variations of monoamines were assessed in the nucleus accumbens. Administration of interleukin-1beta did not affect extracellular accumbal dopamine, provoked a modest rise of homovanillic acid, and prevented the decline of dihydroxyphenylacetic acid ordinarily seen in saline treated rats. Also, interleukin-1 provoked a modest increase of extracellular 5-hydroxyindoleacetic acid from the nucleus accumbens. Following exposure to the stress of a series of air-puffs, a still greater increase of accumbal 5-hydroxyindoleacetic acid was evident. In contrast to interleukin-1, systemic administration of interleukin-6 and interleukin-2 both induced marked reductions of interstitial dopamine levels. The air-puff exposure further enhanced these effects in rats that had received the cytokine treatment. As well, interleukin-6 and interleukin-2 were both found to reduce the homovanillic acid response associated with the stress, and interleukin-2 promoted a decline of homovanillic acid levels. Treatment with interleukin-6, like that of interleukin-1, prevented the decline of dihydroxyphenylacetic acid ordinarily observed over time, while interleukin-2 was without effect in this respect. Finally, interleukin-6 provoked a modest rise of 5-hydroxyindoleacetic acid, which was most apparent following air-puff exposure, while administration of interleukin-2 did not affect accumbal 5-hydroxyindoleacetic acid. It is suggested that the cytokines may influence the release of biogenic amines in the nucleus accumbens, but the profile of changes were cytokine-specific. As well, it appeared that the cytokines, particularly interleukin-1 and interleukin-6, may act synergistically with the stressor in promoting the amine variations. Systemic administration of cytokines clearly influenced monoamine activity at the nucleus accumbens, a region associated with both rewarding and aversive events. Thus, it may be expected that cytokine treatments may affect behavior. Moreover, it seems that the effects of interleukin-1 and interleukin-6 may be influenced by the presence of stressful stimuli. It ought to be underscored that although cytokines share features with the effects of stressors, most notably the variations of hypothalamic-pituitary-adrenal hormones, the pattern of central neurochemical changes elicited by the cytokines could be distinguished from the amine variations ordinarily associated with stressors.

3,4-Dihydroxyphenylacetic Acid↗

Lower activity of serum peptidases in abstinent alcohol-dependent patients.

This study examines i) the activity of serum prolyl endopeptidase (PEP) and dipeptidlyl peptidase IV (DPP IV) in detoxified alcohol-dependent patients without liver disease versus normal controls, and ii) the relationships between serum DPP IV and PEP activity and the production of cytokines or cytokine receptors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interferon-y (IFN-y), IL-1 receptor antagonist (IL-1RA), and IL-10, and granulocyte-macrophage colony stimulatory factor (GM-CSF). Alcohol-dependent patients had significantly lower serum PEP and DPP IV activity than normal controls. We found that 58.3% and 50.0% of the alcohol-dependent patients, respectively, had PEP and DPP IV activities, which were lower than the mean control values minus 2 SD. There were significant inverse correlations between lowered serum DPP IV and PEP activity and the increased production of IL-6, INF-gamma, IL-IRA, IL-10, and GM-CSF. These results show that lower serum DPP IV and PEP activity may be related to the pathophysiology of alcohol dependence.

Adult↗

Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion.

There is now some evidence that major depression is accompanied by activation of the inflammatory response system. There is also some evidence that antidepressants may suppress the release of cytokines, such as interleukin-1 beta (IL-1 beta) and IL-6 by activated monocytes and IL-2 and interferon-gamma (IFN gamma) by activated T cells. This study was carried out to examine the effects of clomipramine, sertraline, and trazodone on the stimulated production of IFN gamma, a pro-inflammatory cytokine, and IL-10, a negative immunoregulatory cytokine. Whole blood of nine healthy volunteers was stimulated with PHA, 5 micrograms/mL and LPS, 25 micrograms/mL for 72 hr with and without incubation with clomipramine, 10(-6) and 10(-9) M, sertraline, 10(-6) and 10(-8) M, and trazodone, 10(-6) and 10(-8) M. All three antidepressants significantly reduced IFN gamma secretion, whereas clomipramine and sertraline significantly increased IL-10 secretion in culture supernatant. All three antidepressants significantly reduced the IFN gamma/IL-10 ratio. The results suggest that antidepressants, at concentrations in the therapeutical range, have negative immunoregulatory effects through inhibition of IFN gamma and stimulation of IL-10 release.

Adult↗

Potentiation of cholecystokinin and secretin-induced pancreatic exocrine secretion by endogenous insulin in humans.

To investigate the effects of endogenous insulin on pancreatic exocrine secretion in humans, we evaluated the pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct in 21 healthy subjects (14 men and seven women). Samples of pancreatic juices were collected after intravenous injection of either glucose (50%, 40 ml), secretin (0.25 CU/kg), and cholecystokinin-8 (CCK) (40 ng/kg), or a combination of glucose, secretin, and CCK in six 5-min periods. The responses of plasma glucose, insulin, and C-peptide to intravenous administration of glucose were measured. After infusion of glucose, the plasma insulin and C-peptide levels were significantly increased and remained at high levels during 30-min experiments, intravenous administration of secretin and CCK resulted in significant increases of pancreatic secretion including volume, bicarbonate, and protein output. When glucose was simultaneously administered with secretin and CCK, pancreatic secretion was significantly increased, more than the effects achieved by the secretin and CCK. However, glucose alone did not increase basal pancreatic secretion. These observations suggest that endogenous insulin intensifies pancreatic secretion stimulated by secretin and CCK in humans.

Adult↗

The effects of psychological stress on leukocyte subset distribution in humans: evidence of immune activation.

The aim of the present study was to examine the effects of academic examination stress on leukocyte subset distribution in university students. Thirty-eight university students had repeated blood collections for white blood cell differentiation and flow cytometric assay of lymphocytic subsets a few weeks before and after (i.e. two baseline conditions) as well as the day before a difficult academic examination (i.e. stress condition). Flow cytometry was used to determine the number of peripheral blood mononuclear cells (PBMC). In students, who were reactors to psychological stress (criterion based on changes in the Perceived Stress Scale, PSS), but not in stress non-reactors, a significant increase in the number of neutrophils, monocytes, CD8(+), CD2(+)CD26(+), and CD2(+)HLA-DR+ T cells and CD19(+) B cells, and significant reductions in the CD4(+)/CD8(+) T cell ratio were observed in the stress condition. There were significant and positive relationships between the stress-induced changes in perceived stress (PSS scale) and number of leukocytes, neutrophils, CD2(+), CD2(+)CD26(+) and CD2(+)HLADR+ T cells, and CD19(+) B cells. There were significant and negative relationships between the stress-induced changes in the CD4(+)/CD8(+) ratio and the stress-induced changes in the PSS scale. Female students taking oral contraceptives showed significantly higher stress-induced responses in number of leukocytes, neutrophils and CD19(+) B cells than male and female students without use of oral contraceptives. The results suggest that academic examination stress induces changes in the distribution of PBMC, which indicate immune activation and which are probably orchestrated by a stress-induced production of cytokines.

Adult↗

Lower serum zinc in relation to serum albumin and proinflammatory cytokines in detoxified alcohol-dependent patients without apparent liver disease.

Recently, it was reported that there may be an activation of the inflammatory response system in detoxified alcohol-dependent patients without apparent liver disease (AWLD). The aims of the present study were to examine serum zinc (Zn) concentrations, total serum protein (TSP) and patterns obtained in the electrophoretically separated protein fractions in relation to serum interleukin-6 (IL-6) and IL-8 concentrations in detoxified AWLD patients. Zn, TSP, SP electrophoresis, and serum IL-6 and IL-8 concentrations were determined in detoxified AWLD patients and age-matched healthy volunteers. Serum Zn, TSP and the serum concentrations of albumin (Alb) and the beta fraction were significantly lower in detoxified AWLD patients than in healthy volunteers. The percentage of the alpha2 fraction was significantly higher in detoxified AWLD patients. Lower serum Zn in detoxified AWLD patients was attributable to lowered serum Alb. Lower serum Alb was significantly and negatively correlated to increased serum IL-8. The percentage of the alpha1 and alpha2 fractions were significantly and positively related to serum IL-6 and IL-8. The results show that there is an in vivo activation of the inflammatory response system in detoxified AWLD patients and that lower serum Zn may be causally related to lower serum Alb.

Adult↗

Stimulated neutrophils evoke signal transduction to increase vascular permeability in rat lungs.

The mechanisms by which stimulated neutrophils (PMNs) damage pulmonary vascular endothelium were investigated using twenty-four perfused lung preparations isolated from rats. We tested 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) and hemodynamics. To stimulate PMNs, they were gently agitated in a glass vial for 10 seconds. Perfusing lungs with the stimulated PMNs (stimulated group) elicited a 3-fold increase in the filtration coefficient as compared to lungs perfused with unstimulated cells (unstimulated group). This increase in filtration was completely blocked by preincubation of stimulated PMNs with CD18 monoclonal antibody (MoAb group). This increase in filtration coefficient was also completely blocked by GF109203X, a protein kinase C inhibitor (GF group). Pulmonary vascular resistance increased when the stimulated PMNs were injected to the isolated lungs. Although, preincubation of stimulated PMNs with CD18 MoAb successfully blocked and GF109203X partly blocked this increase in pulmonary vascular resistance. The accumulation of stimulated PMNs within the lungs, as assessed by myeloperoxidase (MPO) levels, was blocked by preincubation of stimulated PMNs with CD18 MoAb. However, GF109203X did not decrease MPO levels. These findings suggest that stimulated PMN-induced increases in pulmonary vascular filtration, resulted from endothelial cell injury caused by adhesion to the endothelial cells, evoke intracellular signaling within the endothelial cells.

Animals↗