Biomedical subjects

M Y Sun

Publications and source records attributed to M Y Sun.

8 recordsLinked to original sources

PubMed2001

MHC class I multimers.

T lymphocytes play a key role in the immune response to both foreign and self peptide antigens, which they recognize in combination with MHC molecules. In the past it has been difficult to analyse objectively the specificity, frequency and intensity of T cell responses. The recent application of fluorescent-labelled MHC class I multimers, however, has provided a powerful experimental approach to the direct visualisation of antigen-specific T cells. As a result, our perspective of how T cells respond to both viruses and other antigens in vivo has been greatly enhanced.

Autoimmune Diseases↗

PubMed2001

Differing processing requirements of four recombinant antigens containing a single defined T-cell epitope for presentation by major histocompatibility complex class II.

A set of predictive rules governing the likelihood of generating a particular peptide-major histocompatibility complex (MHC) class II complex from an intact antigen has not been fully elucidated. We investigated the influence of positional and structural constraints in the region of the epitope by designing a set of recombinant antigens that each contained the well-characterized T-cell epitope moth cytochrome c (MCC) (88-103), which is specifically recognized by the monoclonal antibody (mAb) D4 when complexed with H-2Ek. Our model antigens contained MCC(88-103) either peripherally, at or towards the C-terminus, or internally. Their abilities to bind directly to soluble H-2Ek, and the extent of D4 epitope formation from them by antigen processing-competent and -incompetent cell lines, were determined. Here we report that three of these four antigens yielded MCC(88-103)/H-2Ek complexes independently of the conventional MHC class II antigen-processing and presentation pathway, and in each case the epitope was carried peripherally; two bound directly as intact proteins, probably as a result of spatial separation of the epitope from the major globular domain, and one was processed to peptide by a cell-surface protease. One protein, which carried the epitope inserted into an internal loop, acted as a conventional processing-dependent MCC(88-103) delivery vehicle. Thus, this epitope has different presentation requirements depending on its context. These antigens constitute a panel whose framework could be modified to further define predictive rules for antigen processing for presentation through the different MHC class II complex-generating pathways.

Animals↗

PubMed1999

An inhibitor of type-1 cyclo-oxygenase in tissues from human pregnancy.

BACKGROUND: Previous work has shown that first trimester human decidua contains a protein which directly inhibits the activity of type-1 cyclo-oxygenase (COX-1). METHODS: Activity assays for cyclo-oxygenase types I and II were developed. Cell cytosol was prepared from a number of different sources: human placenta and decidua (first and third trimester), two placental cell-lines (BeWo and TCL-1), an endometrial stromal cell-line and K562 erythroleukemia cells. The effects of all cytosols on activity of type I cyclo-oxygenase, and of cytosols from BeWo choriocarcinoma and decidual cells on type II enzyme, were tested. RESULTS: Cytosols from first trimester human placenta, two placental cell-lines, an endometrial stromal cell-line and K562 erythroleukemia cells all inhibited the type I enzyme. The inhibitor protein could not be detected in third trimester human decidual cells after labor, and was present only at very low levels in third trimester decidua prior to the onset of labor. Cytosols from BeWo and decidual cells had no effect on the activity of the type-2 cyclo-oxygenase enzyme. CONCLUSIONS: The inhibitor of type I cyclo-oxygenase was not specific to pregnancy-related tissues, and may be a general regulator of this enzyme. Lower levels of inhibitor were present at term, but the physiological significance of this is unclear. The cytosolic inhibitor appears to be specific to the type I enzyme.

Cell Line↗

PubMed1997

Performance of coimmobilized yeast and amyloglucosidase in a fluidized bed reactor for fuel ethanol production.

The performance of coimmobilized Saccharomyces cerevisiae and amyloglucosidase (AG) was evaluated in a fluidized-bed reactor. Soluble starch and yeast extracts were used as feed stocks. Conversion of soluble starch streams to ethanol has potential practical applications in corn dry and wet milling and in developmental lignocellulosic processes. The biocatalyst performed well, and demonstrated no significant loss of activity or physical integrity during 10 wk of continuous operation. The reactor was easily operated and required no pH control. No operational problems were encountered from bacterial contaminants even though the reactor was operated under nonsterile conditions over the entire course of experiments. Productivities ranged between 25 and 44 g ethanol/L/h/. The experiments demonstrated that ethanol inhibition and bed loading had significant effects on reactor performance.

Bioreactors↗

PubMed1994

An endogenous inhibitor of prostaglandin synthesis in human decidua.

Human first trimester decidual tissue has been reported to contain an inhibitor of cyclo-oxygenase enzyme, but a careful reading of the literature indicates that the inhibitor may be human albumin. Our own studies also showed that high levels of albumin were present in samples from homogenised decidual tissues. We therefore digested the tissue to obtain isolated cells and washed them extensively to minimise contamination with blood. Homogenates of such cells did not bind arachidonic acid, and inhibited cyclo-oxygenase enzyme-1 (COX-1) activity. The cellular factor inhibited COX-1 at concentrations of 60-100 micrograms protein/ml, and was therefore more potent than human albumin (0.5-2.0 mg/ml). The inhibitory activity was lost after heat treatment (100 degrees C for 10 mins) and after digestion with trypsin or papain, but was resistant to mercaptoethanol and urea. Preliminary data indicated that the protein had a molecular weight > 30 kD.

Arachidonic Acid↗

PubMed1993

The effects of interleukins 1 alpha and 1 beta on prostaglandin production by cultured human fetal membranes.

The effects of IL-1 alpha and IL-1 beta on cultured human fetal membranes were studied. These cytokines are known to regulate prostaglandin synthesis by the separated components of the fetal membranes (amnion, chorion and decidua), but their effects on intact tissue are unknown. IL-1 alpha increased PGE2 levels on the fetal side of the membrane, indicating increased production of prostaglandin from the amnion, but had little effect on levels of PGE2 on the maternal side of the membrane. Low levels of IL-1 beta (0.1-1.0 ng/ml) increased PGE2 levels on the fetal side of the membrane, and also increased the production of PGE2 metabolites and PGF2 alpha, suggesting that this cytokine stimulated the decidua as well as the amnion. High concentrations of both cytokines appeared able to stimulate prostaglandin production by the side of the membrane opposing that to which they were added, but it is not clear whether this was mediated by factors released by the stimulated membrane, or by direct transfer of small quantities of cytokines through the membrane. Taken together, these results indicate that IL-1 beta was a potent stimulator of the synthesis of prostaglandins by decidua and by amnion, whereas IL-1 alpha only stimulated the amnion.

Culture Techniques↗

PubMed1993

Effects of interleukin-6 and tumor necrosis factor-alpha on prostaglandin production by cultured human fetal membranes.

In this study we investigated the effects of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on prostaglandin production by cultured human fetal membranes. These cytokines stimulate prostaglandin synthesis by isolated components of human fetal membranes, but their effects on the intact tissue comprising amnion, chorion and decidua were not known. TNF-alpha added to the maternal side of the membrane activated decidual production of PGF2 alpha but had no effects on synthesis of PGE2 or PGE2 metabolites. Addition of TNF-alpha to the fetal side of the membrane increased production of PGE2 by amnion and PGE2 metabolites from chorion. The addition of IL-6 to the fetal or the maternal side of the membrane increased production of PGE2 from amnion and PGE2m from chorion, suggesting that IL-6 might pass through the fetal membrane. IL-6 had no effect on decidual PGF2 alpha production. These results suggest that TNF-alpha may be involved in labor by increasing decidual prostaglandin synthesis, whereas IL-6 is less likely to have a role.

Amnion↗

PubMedDate not supplied

Nebulized nitroglycerin in children with pulmonary hypertension secondary to congenital heart disease.

Pulmonary hypertension continues to be a major cause of morbidity and mortality, despite new treatments. Since inhaled nitric oxide has been reported to be effective in some cases, we investigated using nebulized nitroglycerine to treat pulmonary hypertension in children with congenital heart disease. Four children (ages 6-72 months) with severe pulmonary hypertension secondary to congenital heart disease (all with membranous ventricular septal defect, undergoing cardiac catheterization) were given 3 cc of nebulized normal saline over 10 min as placebo control, followed by nebulized nitroglycerine (20 micrograms/Kg in 3 cc normal saline). Normal saline administration did not elicit any change, but nitroglycerine administration resulted in the following changes (mean +/- SE, paired statistics): systolic pulmonary artery pressure from 68 +/- 8 to 53 +/- 6 at 10 min into treatment (P 0.006), mean pulmonary artery pressure 47 +/- 4 to 38 +/- 4 (P 0.005), heart rate 131 +/- 8 to 127 +/- 7 (P 0.13), systolic blood pressure 85 +/- 8 to 88 +/- 3 (P 0.7), mean blood pressure 59 +/- 6 to 63 +/- 4 (P 0.5). These results indicate that nebulized nitroglycerine may be an effective, easy to administer, inexpensive, and safe alternative for treatment of severe pulmonary hypertension in children with congenital heart disease, especially in areas where other treatments such as extracorporeal membrane oxygenation or inhaled nitric oxide are inaccessible.

Aerosols↗