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Biomedical subjects

S Wei

Publications and source records attributed to S Wei.

At least 199 records · Page 11Linked to original sources

Immunomodulation in vivo by the Mycoplasma arthritidis superantigen, MAM.

Mycoplasma arthritidis produces a potent superantigen (MAM) that activates specific murine and human T lymphocytes to proliferate and secrete lymphokines. We show here that MAM also influences both T- and B-cell functions in vivo. Lymphocytes from mice injected with MAM exhibit a suppression of proliferative responses to MAM in vitro but only a partial suppression of responses to other mitogens. This T-cell anergy not only decreased contact sensitivity to dinitrofluorobenzene but also prolonged survival of skin transplants. In contrast, B-cell reactivity is increased following in vivo injection of MAM, as evidenced by enhanced antibody responses to sheep red blood cells and ovalbumin. Also, there is a marked decrease in the ability of splenocytes from MAM-injected mice to produce interleukin-2 (IL-2) but a marked increase in their ability to produce IL-4 and IL-6. The combined results suggest that MAM induces a lymphokine profile that favors activation of B-cell functions, with a resulting potential for triggering of autoimmune disease.

Acquired Immunodeficiency Syndrome↗

Retinol release by activated rat hepatic lipocytes: regulation by Kupffer cell-conditioned medium and PDGF.

In normal liver, lipocytes are the principal reservoir for retinoids, which are stored as retinyl esters. In liver injury, lipocytes activate into myofibroblast-like cells, which lack retinoid. We examined mechanisms of retinoid loss using a culture model in which lipocyte activation is provoked by exposure to Kupffer cell-conditioned medium (KCM) (S.L. Friedman and M. J. P. Arthur, J. Clin. Invest. 84: 1780-1785, 1989). In lipocytes exposed to KCM, there was approximately 11-fold more retinol in medium than in untreated cells, without release of retinyl esters. Both bile salt-dependent and -independent retinyl ester hydrolase was entirely intracellular, suggesting that the increase in retinol was due to intracellular hydrolysis; activity of bile salt-independent hydrolase was increased in KCM-treated lipocytes. Release of retinol was serum dependent and inhibited 40% by antibodies to platelet-derived growth factor (PDGF). The addition of 10 nM PDGF to serum-free KCM also induced retinol release. Lipocyte expression of mRNAs for cellular retinol-binding protein, retinoic acid receptor (RAR)-alpha, and RAR-beta was unchanged after exposure to KCM. In summary, activation of cultured lipocytes by KCM is accompanied by serum- and PDGF-dependent release of retinol; a similar mechanism may underlie retinoid loss by activated lipocytes in vivo.

Adipose Tissue↗

Lymphocyte dysfunction in injured adults with elevated Candida antigen titers.

BACKGROUND: Lymphocytes play an important role in the activation of polymorphonuclear neutrophil (PMN) antimicrobial functions. This study was undertaken to evaluate the ability of lymphocytes from severely injured adults with elevated Candida antigen titers to activate the anticandidal function of normal PMNs. METHODS: Lymphocytes from 13 injured adults with elevated Candida antigen titers (titer+) were isolated and incubated with or without heat-killed C. albicans. After a 48-hour incubation, cell culture supernatants were harvested and tested for the ability to activate the anticandidal function of normal PMNs. Lymphocytes from 13 volunteers and 13 injury-matched patients with negative Candida antigen titers (titer-) were studied for comparison. RESULTS: The patients with titer+ and titer- were well matched in terms of age, sex, Injury Severity Score, units of blood transfused, and length-breadth of antibiotic therapy. Patients with titer+ had a higher incidence of bacterial infections than did patients with titer-. Only 2 of the 13 patients with titer+ had a positive Candida culture. Lymphocytes from the volunteers and patients with titer- released large amounts of a PMN-activating factor(s) when exposed to C. albicans. Lymphocytes from the patients with titer+ were defective in their ability to release this activating factor(s) after exposure to C. albicans. CONCLUSIONS: Although culture evidence of Candida was uncommon, injured adults with elevated Candida antigen titers have lymphocyte dysfunction and often suffer documented bacterial infections.

Adult↗

Cytochrome P-450 arachidonic acid epoxygenase. Regulatory control of the renal epoxygenase by dietary salt loading.

The rat kidney microsomal epoxygenase catalyzed the asymmetric epoxidation of arachidonic acid to generate as major products: 8(R),9(S)-, 11(R),12(S)- and 14(S),15(R)-epoxyeicosatrienoic acids with optical purities of 97, 88, and 70%, respectively. Inhibition studies utilizing a panel of polyclonal antibodies to several rat liver cytochrome P-450 isoforms, indicated that the renal epoxygenase(s) belongs to the cytochrome P-450 2C gene family. Dietary salt, administered either as a 2-2.5% (w/v) solution in the drinking water or as a modified solid diet containing 8% NaCl (w/w), resulted in marked and selective increases in the renal microsomal epoxygenase activity (416 and 260% of controls, for the liquid and solid forms of NaCl, respectively) with no significant changes in the microsomal omega/omega-1 oxygenase or in the hepatic arachidonic acid monooxygenase reaction. Immunoblotting studies demonstrated that dietary salt induced marked increases in the concentration of a cytochrome P-450 isoform(s) recognized by polyclonal antibodies raised against human liver cytochrome P-450 2C10 or rat liver cytochrome P-450 2C11. Comparisons of the stereochemical selectivity of the induced and non-induced microsomal epoxygenase(s) with that of purified rat liver cytochrome P-450 2C11 suggest that the salt-induced protein(s) is catalytically and structurally different from liver cytochrome P-450 2C11. The in vivo significance of dietary salt in regulating the activities of the kidney endogenous arachidonic acid epoxygenase was established by the demonstration of a salt-induced 10-20-fold increase in the urinary output of epoxygenase metabolites. These results, in conjunction with published evidence demonstrating the potent biological activities of its metabolites, suggest a role for the epoxygenase in the renal response to dietary salt.

8,11,14-Eicosatrienoic Acid↗

Arachidonic acid epoxygenase: structural characterization and quantification of epoxyeicosatrienoates in plasma.

Gas chromatographic/mass spectroscopic and chiral analysis showed the presence of enzymatically derived 8,9-, 11,12- and 14,15-EET in rat plasma (2.8:1:3.4 molar ratio, respectively; 10.2 +/- 0.4 ng total EET/ml plasma). Greater than 90% of the plasma EETs was esterified to the phospholipids of circulating lipoproteins. The lipoprotein fraction with the highest EET concentration was LDL (8.1 +/- 0.9 ng/mg of protein) followed by HDL and VLDL (3.5 +/- 0.1 and 1.9 +/- 0.3 ng/mg of protein, respectively). In light of the biological activities of the EETs, these results suggest a potential systemic function for the cytochrome P-450 epoxygenase.

8,11,14-Eicosatrienoic Acid↗

Resolution of dihydroxyeicosanoates and of dihydroxyeicosatrienoates by chiral phase chromatography.

A chromatographic method is described for the direct enantiomeric characterization of 5,6-, 8,9-, 11,12-, and 14,15-vic-dihydroxyeicosatrienoic acids (DHETs), metabolites of the cytochrome P-450 arachidonate epoxygenase pathway, and of their corresponding saturated vic-dihydroxyeicosanoic acids. Following esterification, the individual methyl or pentafluorobenzyl esters are resolved by chiral-phase chromatography utilizing a Chiralcel OC or OD column. This methodology will find analytical and preparative applications since it is simple and efficient and preserves, intact, the diol functionality.

8,11,14-Eicosatrienoic Acid↗

Recombinant interleukin-8 induces changes in cytosolic Ca2+ in human neutrophils.

Activation of polymorphonuclear leukocytes (PMNL) by most soluble stimulants is associated with a marked increase in cytosolic free Ca2+ ([Ca2+]i). Interleukin-8 (IL-8), a monocyte-derived neutrophil chemotactic factor and potent neutrophil-activating cytokine, effectively enhanced the resting free [Ca2+]i within human PMNL in a dose-dependent manner (maximal effect with 100 ng/mL). The increase in [Ca2+]i was substantially (55%) inhibited in the absence of extracellular Ca2+. Thus, the increase was due to extra- and intracellular cooperative mobilization of Ca2+, as supported by the reduced effect of IL-8 on [Ca2+]i after quenching with Mn2+. Granulocyte-macrophage colony-stimulating factor and interferon-gamma failed to induce a change in [Ca2+]i, suggesting that they may operate through different signal pathways. Pretreatment with Bordetella pertussis toxin largely inhibited the IL-8-induced change in [Ca2+]i. Thus, IL-8-induced cooperative mobilization of intra- and extracellular Ca2+ leads to a net Ca2+ influx into the cytoplasm through a process mediated by a guanosine triphosphate-binding protein.

Calcium↗

Lymphokine-activated killer cell regulation of T-cell-mediated immunity to Candida albicans.

Monocytes are important accessory cells in the activation of T cells for specific antigen recognition yet little is known of their regulation. We demonstrated here that interleukin-2 (IL-2)-induced human lymphokine-activated killer (LAK) cells can inhibit monocyte antigen presentation, depending on the state of differentiation of the monocytes. Adherent monocytes cultured for 4 days in medium or granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to equally process and present intact Candida albicans to autologous Percoll gradient-isolated T cells, as measured by [3H]thymidine uptake. However, only the GM-CSF-cultured monocytes were functionally inhibited by autologous 4-day IL-2-induced LAK cells. Even soluble candidal cell wall mannoprotein antigens could not be presented by these monocytes after exposure to LAK cells. Pretreatment of these monocytes with LAK cells for 1 h, followed by subsequent removal of the nonadherent LAK cells, was sufficient to cause significant inhibition, with maximal inhibition observed after 4 h. Northern (RNA) blot analysis indicated that mRNA expression for IL-1 alpha and IL-1 beta in response to C. albicans stimulation was also down-regulated in GM-CSF-cultured monocytes exposed to LAK cells. Interestingly, freshly isolated, Percoll gradient-purified large granular lymphocytes did not suppress antigen presentation in GM-CSF-treated monocytes. Another important finding was the inability of LAK cells to suppress the ability of freshly isolated or gamma interferon-cultured monocytes, which are resistant to LAK cell-mediated lysis, to present antigen to T cells. In contrast, IL-3 was similar to GM-CSF in inducing LAK cell susceptibility in monocytes. Taken together, these results indicated that IL-2 can induce LAK cells to down-regulate antigen presentation function in a select set of monocytes that have been activated by colony-stimulating factor (GM-CSF and IL-3) but not by gamma interferon. LAK cells may therefore play an important role in regulation of monocytes and their function, depending on their differentiation state.

Antigen-Presenting Cells↗

Effects of endothelin-1 and conversion of big endothelin-1 in the isolated perfused rabbit lung.

We examined the effects of endothelin-1 (ET-1) on pulmonary hemodynamic and transvascular fluid filtration and the conversion of big endothelin-1 (big ET-1), a precursor of ET-1, in isolated perfused rabbit lungs at constant vascular and airway pressures. Furthermore we examined whether ET-1 contributes to cyclooxygenase metabolism. The perfusate flow decreased significantly after bolus administration of 1 or 0.1 nmol of ET-1. Lung weight did not increase throughout the experimental period. Big ET-1- (1 nmol) induced decrease in the flow was slow in developing, although the maximum response was comparable to that induced by the same dose of ET-1. The concentration of bit ET-1 in the perfusate progressively decreased, while that of ET-1 increased in a time-dependent manner. Phosphoramidon, an inhibitor of metalloproteinase, suppressed the pressor effect of big ET-1 (P less than 0.01) and the increase in the concentration of ET-1 in the perfusate (P less than 0.05). The present findings provide the first evidence suggesting that the potent vasocontractile effect of big ET-1 in pulmonary circulation can be attributed to the production of ET-1 by the conversion from big ET-1 in the vascular bed. ET-1-induced perfusate flow changes were not affected by indomethacin, and the concentration of 6-ketoprostaglandin F1 alpha, a metabolite of prostacyclin, did not increase after ET-1 administration.

Animals↗

[Effects of mixture of Astragalus membranaceus, Fructus Ligustri lucidi and Eclipta prostrata on immune function in mice].

A Chinese medicine mixture containing Astragalus membranaceus, Fructus Ligustri Lucidi and Eclipta prostrata(AFE), was fed to mice 9g/kg, 20g/kg, respectively for seven days. Observe the effects of AFE on the immune function in mice. The experiment showed that the two dosages of AFE could obviously raise the conversion percentage of lymphocytes (P < 0.01) and serum IgG level (41%-47%) of the mice. The weights of the thymus and spleensed increased in the two groups compared with those in the normal control. The larger dosage of AFE could also raise activity of Adenosine Deaminase (ADA) obviously (P < 0.01). AFE turned out a resistance to the immunosuppressive effect caused by cyclophosphamide.

Adenosine Deaminase↗

[Relationship between height, collagen metabolism, hair zinc and excessive fluoride intake].

After eliminating confounding factors, the study was made on the relationship between height, collagen metabolism, hair zinc and excessive fluoride intake. 140 schoolchildren aged 12-13 years born and reared in endemic fluorosis areas were surveyed. The results were as follows: 1. The average height of children with dental fluorosis III degree (DF III degree) was appreciably smaller than that of children without dental fluorosis. Among children with excessive fluoride intake, a negative correlation between the height and fluoride level in staple foods was seen. 2. The more the fluoride ingested, the higher the urinary THP excreted, showing that fluoride intoxication interfered with the collagen metabolism. 3. Among children with excessive fluoride intake, the height showed negative correlation with urinary THP/Cr, suggesting that the effect of fluoride on collagen metabolism indicated the mechanism of height retardation. 4. As compared to control group with the excessive fluoride intake but without dental fluorosis group, there was a significant reduction in hair zinc in group with DF III degree, suggesting that the zinc in the body decreased because of zinc metabolism disturbance by excessive fluoride intake. But among cases with excessive fluoride intake, no appreciable correlation between hair zinc and height was found. Therefore, it could not be confirmed that the effect of fluoride on zinc metabolism affected the height development.

Adolescent↗

[Cost-effectiveness analysis of short-term course and regular course of antithyroid drug therapy for Graves' disease].

One hundred and- eighteen newly diagnosed patients with Graves' disease were treated by tapazole for 6 months (short-term course) and followed up for another 12 months. Forty three percent remission rate was found in this group. A regular course of antithyroid drug therapy for 1.5-2 years with 50% remission rate was taken as control. Cost-effectiveness analysis was made to compare the cost in the two different kinds of therapy. The results showed that the total costs of the treatment per 100 cases were 17,746 yuan for the short-term therapy and 30,708 yuan for the regular therapy, with an average of 412.7 yuan and 614.2 yuan per case respectively. In comparison with the short-term therapy, the regular course could remit 7 more cases at a cost of 12,962.40 yuan, with an average of 1851.80 yuan per case. Therefore, the cost was high by prolonged course of therapy to increase slightly remission rate, although it could remit a few more cases. This study suggests that six-month treatment is preferable for those who live in the rural or remote area where the economy was less developed. A longer course of therapy may be unnecessary for those who have been treated by antithyroid drugs for 6 months or longer and are predicted to obtain a possible prolonged remission.

Cost-Benefit Analysis↗