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Biomedical subjects

S Sun

Publications and source records attributed to S Sun.

At least 19 recordsLinked to original sources
PubMed2000

Development and comparison of two 3T3-L1 adipocyte models of insulin resistance: increased glucose flux vs glucosamine treatment.

Insulin resistance can be induced in vivo by intravenous infusion of glucosamine or in cells by incubation with glucosamine. However, a publication (Hresko, R. C., et al. (1998) J. Biol. Chem. 273, 20658-20668) suggests a trivial explanation of glucosamine-induced insulin resistance whereby intracellular ATP pools are depleted presumably due to the phosphorylation of glucosamine to glucosamine 6-phosphate, a hexosamine pathway intermediate. The reduced ATP level impaired insulin receptor (IR) autophosphorylation and tyrosine kinase activity toward substrates. The present work describes the development and comparison of two methods for inducing insulin resistance, by treating 3T3-L1 adipocytes overnight using either 25 mM glucose/5 nM insulin or 2 mM glucosamine. Under these conditions basal glucose transport rates were comparable with controls. Insulin-stimulated 2-deoxyglucose uptake, however, was reduced by approximately 45% in response to both high glucose/insulin and glucosamine treatment, relative to control cells. The total relative amounts of the insulin-responsive glucose transporter, Glut4, remained constant under both treatment conditions. The relative phosphotyrosine (Tyr(P)) contents of the insulin receptor and its substrate 1 (IRS-1) were assessed in whole cell homogenates. With both methods to induce insulin resistance, IR/IRS-1 Tyr(P) levels were virtually indistinguishable from those in control cells. Insulin-stimulated phosphorylation of Akt on Ser(473) was not impaired in insulin-resistant cells. Furthermore, the relative Tyr(P) content of the PDGF receptor was comparable in high glucose/insulin- or glucosamine-treated 3T3-L1 adipocytes upon subsequent challenge with PDGF. Finally, the relative amounts of glutamine:fructose-6-phosphate amidotransferase and O-linked N-acetylglucosamine transferase, two important hexosamine pathway enzymes, were similar in both treatments when compared with controls. Thus, 3T3-L1 adipocytes can be used as a model system for studying insulin resistance induced by increased influx of glucose. Under appropriate experimental conditions, glucosamine treatment can mimic the effects of increased glucose flux without impairment of tyrosine phosphorylation-based signaling.

3T3 Cells↗
PubMed2000

Mycophenolate mofetil treatment reduces atherosclerosis in the cholesterol-fed rabbit.

Immune/inflammatory responses of arterial vessel wall constituents to lipid metabolic disturbances have been postulated to contribute to the pathogenesis of atherosclerosis. Mycophenolate mofetil (MMF), an antiproliferative agent used in clinical transplantation, has been shown to inhibit smooth muscle cell (SMC) proliferation and decrease the recruitment of monocytes into sites of chronic inflammation. This study was conducted to determine the effect of MMF on atherosclerotic plaque development after cholesterol-induced injury. New Zealand white rabbits were fed a high-cholesterol diet containing 0.5% cholesterol and 8% peanut oil. The experimental group (n = 10) was given MMF (80 mg/kg/day subcutaneously); the control group (n = 10) received placebo injections. The aortas were harvested at 12 weeks for immunohistochemical analyses. SMCs were identified by reactivity with a monoclonal antibody (mAb) to alpha smooth muscle actin. Monocytes/macrophages were detected with mAb RAM 11. Cross-sectional areas of the media and neointima were measured using computer-assisted image analysis. The density of SMCs and macrophage/foam cells within the neointima was calculated by dividing the number of cells by the area of the plaque. Total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein were significantly increased compared with levels before the initiation of a high-cholesterol diet, but there were no significant differences between the MMF-treated and untreated groups. Neointimal area in aortic tissue sections of the MMF-treated group (0.586 +/- 0.602 mm(2)) was significantly lower when compared with that in control animals (1.082 +/- 0.621 mm(2)) (P < 0.05). The densities of neointimal SMCs and monocytes/macrophages in the control group were 778 +/- 293 and 341 +/- 90 cells/mm(2), respectively. MMF treatment significantly reduced the number of neointimal SMCs (506 +/- 185 cells/mm(2)) (P < 0.05). The number of monocytes/macrophages was also reduced after MMF treatment (260 +/- 124 cells/mm(2)) but not significantly. Our results demonstrate that the administration of MMF significantly reduced neointimal SMC accumulation and plaque development in a hypercholesterolemic model of atherosclerosis.

Animals↗
PubMed2000

Trace element levels in drinking water and cognitive function among elderly Chinese.

The relation between trace element levels in drinking water and cognitive function was investigated in a population-based study of elderly residents (n = 1,016) in rural China in 1996-1997. Cognitive function was measured using a Chinese translation of the Community Screening Interview for Dementia. A mixed effects model was used to evaluate the effect of each of the elements on cognitive function while adjusting for age, sex, and educational level. Several of the elements examined had a significant effect on cognitive function when they were assessed in a univariate context. However, after adjustment for other elements, many of these results were not significant. There was a significant quadratic effect for calcium and a significant zinc-cadmium interaction. Cognitive function increased with calcium level up to a certain point and then decreased as calcium continued to increase. Zinc showed a positive relation with cognitive function at low cadmium levels but a negative relation at high levels.

Age Distribution↗
PubMed2000

Vinyl benzenes as dienes in mild solid-phase Diels-Alder reactions

Wang resin-bound intermediates derived from Fmoc-L-phenylalaninal and Fmoc-L-valinal, and a resin supported Horner-Wadsworth-Emmons reaction, were treated with cinnamaldehyde derivatives, acetic acid, and borohydride to give secondary amines which were subsequently benzoylated to afford various derivatives of 3. Heating 3 at 95 degrees C induced cycloaddition reactions and produced 4 as the major product. Compounds 3 which were derived from 4-methoxycinnamaldehyde were more reactive, but did not give 4 and 4-7g. The direct cleavage of 3b using TFA led to the isolation of cycloaddition-demethylation product 10. The derivative of 3, which contained an electron-withdrawing nitro group on the phenyl ring, produced a single diastereomer of 4. The Diels-Alder cycloaddition between two electron-deficient counterparts showed similar reactivity to that of the reactions which have a normal complementary electron-demand.

Journal Article↗
PubMed2000

Recognition of flexible peptides in water by transition metal complexes.

This paper describes the design, synthesis, and evaluation of transition metal complexes capable of recognizing flexible histidine-containing peptides in aqueous medium (25 mM HEPES buffer, pH = 7.0, 25 degrees C). When the pattern of metal ions on a complex matches with the pattern of histidine moieties on the peptide, strong interaction (K = 1.2 x 10(6) M-1) can be achieved. The complex was highly selective (> 200:1) in discriminating similar flexible peptides differing only by one glycine unit.

Glycine↗
PubMed2000

T-cell proliferation in vivo and the role of cytokines.

Unlike typical naive T cells, T cells with an activated (CD44hi) memory phenotype show a rapid rate of proliferation in vivo. The turnover of memory-phenotype CD8+ T cells can be considerably augmented by injecting mice with various compounds, including polyinosinic polycytidylic acid, lipopolysaccharide and immunostimulatory DNA (CpG DNA). Certain cytokines, notably type I (alpha, beta) interferons (IFN-I), have a similar effect. These agents appear to induce proliferation of CD44hi CD8+ cells in vivo by an indirect process involving production of effector cytokines, possibly interleukin-15, by antigen-presenting cells. Although none of the agents tested induces proliferation of naive-phenotype T cells, IFN-I has the capacity to cause upregulation of surface markers on purified naive T cells. Depending upon the experimental conditions used, IFN-I can either inhibit or enhance primary responses of naive T cells to specific antigen.

Animals↗
PubMed2000

Monodisperse FePt nanoparticles and ferromagnetic FePt nanocrystal superlattices

Synthesis of monodisperse iron-platinum (FePt) nanoparticles by reduction of platinum acetylacetonate and decomposition of iron pentacarbonyl in the presence of oleic acid and oleyl amine stabilizers is reported. The FePt particle composition is readily controlled, and the size is tunable from 3- to 10-nanometer diameter with a standard deviation of less than 5%. These nanoparticles self-assemble into three-dimensional superlattices. Thermal annealing converts the internal particle structure from a chemically disordered face-centered cubic phase to the chemically ordered face-centered tetragonal phase and transforms the nanoparticle superlattices into ferromagnetic nanocrystal assemblies. These assemblies are chemically and mechanically robust and can support high-density magnetization reversal transitions.

Journal Article↗
PubMed2000

Paired-pulse modulation at individual GABAergic synapses in rat hippocampus.

1. Unitary inhibitory postsynaptic currents (uIPSCs) were recorded in synaptically coupled pairs of CA1 hippocampal interneurons and pyramidal neurons in rat brain slices by using dual patch-clamp techniques. Paired-pulse modulation of uIPSCs at individual GABAergic synapses was tested. 2. GABAergic synapses could be divided into two subgroups, high and low failure, depending on their failure rate. 3. The external Ca2+ levels modulate the failure rate of uIPSCs. In 0.51 mM Ca2+, low-failure pairs had a high-failure characteristic, whereas high-failure pairs had a low-failure characteristic in 8 mM Ca2+. The results suggest that uIPSC failures result from the Ca2+-dependent release mechanism rather than axon propagation failures. 4. Paired-pulse facilitation (PPF) occurred in high-failure pairs when the interspike interval was 20 ms. Paired-pulse depression (PPD) was not predominant in high-failure pairs. 5. Potency of uIPSCs, the average amplitude of non-failure events, was enhanced by PPF, suggesting that multiple synapses connect each pair. Differing numbers of activated synapses contributed to the variable amplitude of uIPSCs from a given pair. 6. PPD occurred in low-failure pairs at the tested range of interspike intervals (20-200 ms). The uIPSC2 after a large uIPSC1 was smaller than the uIPSC2 after a small uIPSC1, suggesting that PPD is use dependent and due to a decrease in the quantal content (m) after the first release. 7. In 8 mM Ca2+, PPD occurred in high-failure pairs and was larger in low-failure pairs, suggesting that the occurrence of PPF or PPD depends on the baseline release probability. 8. The GABAB receptor antagonist CGP 55845A (5 microM) decreased the baseline release probability of inhibitory synapses and attenuated PPD indirectly, rather than by blocking presynaptic GABAB autoreceptors.

Animals↗
PubMed2000

Stimulation of memory T cells by cytokines.

Mature T cells can be classified on the basis of cell surface markers into naïve- and memory-phenotype cells. These phenotypically-defined subsets exhibit distinct kinetic behaviour in vivo. Thus, naïve-phenotype T cells persist long-term in a non-dividing state, while memory-phenotype T cells include cycling cells and have a more rapid rate of turnover. We have investigated the possibility that the different kinetic behaviour of naïve- and memory-phenotype T cells reflects a differential responsiveness to cytokines. It was discovered that memory-, but not naïve-, phenotype T cells were stimulated to proliferate by a variety of infection-induced cytokines. These results suggest that cytokines contribute to the high background rate of turnover exhibited by memory T cells.

Animals↗
PubMed2000

Cytokine production by sinus lavage, bronchial lavage, and blood mononuclear cells in chronic rhinosinusitis with or without atopy.

BACKGROUND: Chronic sinus inflammation may be determined partly by a balance of proinflammatory and counterregulatory cytokines and other mediators in the sinus. However, their mechanistic roles in chronic rhinosinusitis (CRS) are not well understood. OBJECTIVE: To evaluate production of proinflammatory (interferon gamma [IFN-gamma] and interleukin [IL] 12) and counterregulatory cytokines (IL-10 and IL-4) by sinus lavage (SL), bronchial lavage (BL), and peripheral blood mononuclear (PBMN) cells in patients with CRS. METHODS: We analyzed SL, BL, and PB samples obtained at surgery from 26 patients with CRS. Cytokine production was determined by culturing cells with or without stimuli. The results were evaluated in comparison with other inflammatory variables (cytologic findings, total protein, IgG, and lactose dehydrogenase), bacterial cultures, and clinical features. RESULTS: Production of IFN-gamma by SL cells was variable and did not correlate with other inflammatory variables, microbes grown, IL-10/IL-12p40 production by SL cells, or IFN-gamma production by BL or PBMN cells. Production of IL-4 by lavage cells was undetectable. None of 10 patients with elevated IFN-gamma production (>800 pg/10(6) SL cells with mitogen stimuli) had allergic rhinitis, whereas 12 of 16 patients with low IFN-gamma production (<500 pg/10(6) SL cells) had allergic rhinitis with positive reactivity to common aeoroallergens. There was no significant difference in other variables measured between low and high IFN-gamma production groups. CONCLUSIONS: Elevated IFN-gamma production by SL cells may indicate much less possibility of allergic rhinitis in patients with CRS, but other variables measured did not differ in patients with high or low IFN-gamma production by SL cells.

Adult↗
PubMed2000

Interferon gamma levels in the sinus, ear, and airway in a rabbit sinusitis model induced by Bacteroides inoculation.

BACKGROUND: Previously, we found minimal bacterial dissemination and no evidence of systemic inflammation in a rabbit sinusitis model in which the left maxillary sinus was inflamed by Bacteroides inoculation with the ostium closed. However, we observed an increase in anti-Bacteroides IgG antibodies in the contralateral sinus, lower airway, and middle ear, with an apparent increase in interferon gamma (IFN-gamma) messenger RNA expression in the ear and sinus mucosa. OBJECTIVE: To evaluate how IFN-gamma production in the upper and lower airway is associated with localized bacterial sinusitis. DESIGN: Interferon gamma levels were measured in lavage solutions from the sinus, airway, and middle ear and in serum at 1, 2, 3, and 4 weeks following bacterial inoculation. SUBJECTS: The subjects were 6 rabbits at each time point. The controls were untreated (n = 5) and sham-operated (n = 4-5) rabbits at 2 and 4 weeks. INTERVENTION: Bacteroides fragilis (10(8) plaque-forming units) was inoculated into the left maxillary sinus. RESULTS: Interferon gamma levels in the ear and sinus were less than 0.2 microg/g protein in controls. Following bacterial inoculation into the left sinus, IFN-gamma levels increased up to 10-fold in both sinuses and even more in the middle ear at 3 weeks, independent of bacterial dissemination. Mean +/- SD IFN-gamma levels in the airway (0.3+/-0.28 microg/g protein in controls) were not altered by bacterial inoculation into the sinus. Serum IFN-gamma levels were very low (<0.05 microg/g protein) in most rabbits and were unchanged by bacterial inoculation. CONCLUSIONS: Interferon gamma levels increase in the ear and contralateral sinus in response to localized sinus inflammation, indicating concerted mucosal proinflammatory immune responses in the upper airway. Such responses may lead to the aseptic middle ear inflammation often observed in patients with chronic sinusitis.

Animals↗
PubMed2000

Multiple effects of immunostimulatory DNA on T cells and the role of type I interferons.

In addition to stimulating antigen-specific immune responses, infectious agents cause nonspecific activation of the innate immune system, notably up-regulation of costimulatory/adhesion molecules on APCs and cytokine production. In recent years it has become apparent that stimulation of the immune system by microorganisms is a property of a number of different cellular components, including DNA. As discussed earlier and elsewhere in this volume, the DNA of infectious agents--and indeed of all non-vertebrates tested--differs from mammalian DNA in being enriched for unmethylated CpG motifs. With appropriate flanking sequences, CpG DNA and synthetic CpG ODNs cause strong activation of APCs and other cells. In this article we have focussed on the capacity of CpG DNA/ODNs to alter T cell function. Whether these compounds act directly on T cells or function indirectly by activating other cells, especially APCs, is controversial [7, 8, 13, 14]. In contrast to other workers [8], we have yet to find definitive evidence that CpG DNA/ODNs can provide a co-stimulatory signal for purified T cells subjected to TCR ligation ([14] and unpublished data of authors). For this reason we lean to the notion that CpG DNA/ODNs modulate T cell function by inducing activation of APC rather than by acting directly on T cells. When injected in vivo in the absence of specific antigen, CpG DNA/ODNs have two striking effects on T cells, namely (1) induction of overt activation (proliferation) of memory-phenotype CD8+ cells, and (2) partial activation of all T cells, including naïve-phenotype T cells. Both actions of CpG DNA/ODNs are heavily dependent on the production of IFN-I by APC. For memory-phenotype (CD44hi) CD8+ cells, neither CpG DNA nor IFN-I can cause proliferation of purified APC-depleted T cells in vitro. Hence, under in vivo conditions, CpG DNA-induced proliferation of CD44hi CD8+ cells is probably mediated through the production of a secondary cytokine, i.e., by a cytokine that is directly stimulatory for CD44hi CD8+ cells. Based on the available evidence, it is highly likely that the effector cytokine is IL-15. With this assumption, our current model is that proliferation of CD44hi CD8+ cells induced by injection of CpG DNA/ODNs reflects production of IFN-I which, in turn, leads to synthesis of IL-15. Which particular cell types produce these two cytokines is unclear, although APCs are probably of prime importance. In addition to inducing proliferation of memory-phenotype CD8+ cells via IL-15, the IFN-I induced by CpG DNA/ODNs can also induce partial activation of naive T cells. This form of activation leads to up-regulation of CD69 and other molecules but does not cause entry into cell cycle. It is of interest that the partial activation of naive T cells induced by IFN-I is associated with decreased T proliferative responses. Thus, proliferation of purified naïve T cells elicited by combined TCR/CD28 ligation in vitro is greatly reduced by addition of IFN-I. This inhibitory effect of IFN-I does not influence cytokine production and probably reflects production of cell cycle inhibitors. Surprisingly, except at high doses, IFN-I fails to exert an anti-proliferative effect when T proliferative responses are driven by viable APCs. Indeed, in this situation, IFN-I enhances antigen-specific T proliferative responses, both in vivo and in vitro. This adjuvant effect of IFN-I is presumably a reflection of APC activation, but direct evidence on this issue is still lacking. In this article we have emphasized that contact with CpG DNA/ODNs has multiple effects on T cell function in vivo. Many of these effects seem to be related to the production of certain cytokines by APCs, notably IFN-I and IL-15. It should be stressed, however, that CpG DNA/ODNs probably lead to the production of many other cytokines. Hence, our current models of how CpG DNA/ODNs influence T cell function are undoubtedly oversimplified.

Adjuvants, Immunologic↗
PubMed2000

Farnesylation is involved in meristem organization in Arabidopsis.

Although studies in plant and animal cell culture systems indicate farnesylation is required for normal cell cycle progression, how this lipid modification of select proteins translates into whole-organism developmental decisions involving cell proliferation or differentiation is largely unknown. The era1 mutant of the higher plant Arabidopsis thaliana (L.) Heynh. offers a unique opportunity to understand the role farnesylation may play in regulating various processes during the development of a multicellular organism. Loss of farnesylation affects many aspects of Arabidopsis growth and development. In particular, apical and axillary meristem development is altered and these phenotypes are contingent on the growth conditions.

Abscisic Acid↗
PubMed2000

Using technetium-99M dimercaptosuccinic acid renal cortex scintigraphy to differentiate acute pyelonephritis from other causes of fever in patients with spinal cord injury.

OBJECTIVES: To differentiate acute pyelonephritis (APN) from fever due to other sources in patients with spinal cord injury by using technetium-99m dimercaptosuccinic acid (DMSA) renal cortex scintigraphy (DMSA scan). METHODS: A total of 24 patients with spinal cord injury were admitted with fever. DMSA scans were performed on all patients. The final determination of the cause of the fever was based on the medical history, physical examination, laboratory evaluation, and imaging studies. RESULTS: DMSA scan accurately diagnosed APN in 12 patients with inflammation on the DMSA scan. In 5 patients with scarred lesions on the DMSA scans and in 7 patients with negative DMSA scan, the fever was attributed to other causes. The sensitivity and specificity of the DMSA scan for detecting APN were both 100%. CONCLUSIONS: The DMSA scan is a valuable adjunct in the evaluation of fever in patients with SCI.

Acute Disease↗
PubMed2000

Dietary nucleotides modulate antigen-specific type 1 and type 2 t-cell responses in young c57bl/6 mice.

Mice fed a nucleotide-free (NF) diet have impaired antibody (Ab) responses. The mechanisms responsible for this effect are not understood but may be related to specific changes in T-cell functions. The objective of this study was to examine the effects of dietary nucleotides on serum immunoglobulin-G (IgG) subclass Ab levels and T-cell cytokine production by cells from the lymph nodes draining the site of antigen challenge. C57BL/6 (B6) mice were fed an NF diet or the same diet supplemented with nucleotides (NS diet; 4.74 g nucleotides/kg). Keyhole limpet hemocyanin (KLH; 25 microg/dose), a T-dependent protein neoantigen, was given with incomplete Freund's adjuvant. We administered KLH at 3, 6, and 9 wk to determine primary and secondary responses. Anti-KLH IgG subclass Ab levels were measured 3 wk after the first KLH challenge and 2 wk after the last KLH challenge. T-cell responses in lymph nodes draining the site of KLH challenge were assessed 5 d after the primary and 14 d after the final KLH challenge. We measured mRNA expression and production of interferon-gamma and interleukin-5, type-1 and type-2 T-cell cytokines, respectively. Anti-KLH IgG2a and IgG2b Ab levels were higher in the NS diet group than in the NF diet group after the last KLH challenge. The NS diet group had higher interferon-gamma production and mRNA expression than did the NF diet group after the first KLH challenge. Because increased levels of interferon-gamma and IgG2a/IgG2b Ab reflect a shift toward type-1 responses to antigen stimuli, our results show that dietary nucleotides preferentially enhance type-1 responses to KLH given with incomplete Freund's adjuvant.

Animals↗
PubMed2000

Percutaneous vascular intervention based on gadolinium-enhanced MR angiography.

PURPOSE: To determine if gadolinium-enhanced magnetic resonance angiography (Gd-MRA) could be used to reliably plan percutaneous vascular procedures. PATIENTS AND METHODS: Over the course of 13 months, 31 patients underwent attempted percutaneous intervention solely on the basis of a preceding Gd-MRA study. A total of 49 arterial segments were targeted (28 extremities, 21 visceral). Five segments in four patients were not treated (less impressive disease severity on conventional catheter angiography [CA] in four segments, diffuse intrarenal atherosclerosis in one segment). Interventions attempted were percutaneous transluminal angioplasty (n = 10), angioplasty with stent placement (n = 29), and thrombolysis (n = 3). Interventions were successful in all segments, except two because of the inability to cross an occlusion. RESULTS: Good to strong correlation was noted between Gd-MRA and CA regarding stenosis severity and length and the presence of poststenotic dilatation. MRA underestimated the complexity of stenosis. Subjective quality and preintervention confidence were excellent in the majority of MRA studies and satisfactory in the rest. The overall value in "procedural planning" was judged high in 40 segments, satisfactory in five segments, and poor in four segments. The procedural planning and positive predictive values of MRA were significantly lower for visceral arteries compared to iliac and peripheral arteries. CONCLUSION: In most cases, Gd-MRA reliably yielded the anatomic and diagnostic information necessary to plan percutaneous vascular interventions noninvasively and without iodinated contrast. In the authors' practice, Gd-MRA is becoming a key imaging modality in the workup of patients in whom percutaneous intervention is anticipated.

Adult↗