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Biomedical subjects

Y Shen

Publications and source records attributed to Y Shen.

At least 433 records · Page 24Linked to original sources

[Effect of dexamethasone on the human interleukin-2 receptor alpha chain gene expression].

Glucocorticoids have wide effects on the immune system, the mechanisms of these effects have not been clearly defined. The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) is a critical control point in the T-cell mediated immune response. The effect of dexamethasone, a synthetic glucocorticoid hormone, on IL-2R is unclear in comparison with its inhibition on the accumulation of IL-2 mRNA. Our study shows that dexamethasone increases the basal and PHA-induced mRNA levels of IL-2R alpha gene in Jurkat cells, but it does not affect the expression of reporter gene constructs containing 5' flanking sequences (-482bp/ +16bp or -350bp/+16bp) of the IL-2R alpha gene in PHA activated Jurkat cells. These results indicate that dexamethasone plays a positive regulatory role in the IL-2R alpha gene expression, but the effect is not mediated by the previously identified proximal regulatory elements located between -482bp/+1bp. Meanwhile, our results also provide evidence that the activation mechanism of dexamethasone is different from that of PHA, and that dexamethasone and PHA show a synergistic effect in the induction of IL-2R alpha gene expression.

Cell Line↗

[Regulative effects of cytokines on the expression of cell adhesion molecules on human mesangial cells].

OBJECTIVE: To study the regulative effects of rhIL-1 beta or rhTNF-alpha on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on human mesangial cells (HMC). METHODS: At the 4th, 8th, 16th and 32nd hours after stimulation by rhIL-1 beta (25 ng/ml) or rhTNF alpha (100 ng/ml), the mRNA expression of ICAM-1 and VCAM-1 on HMC was determined with Northern blot, and their protein expression was also tested with cell ELISA analysis. RESULTS: mRNA and protein of both ICAM-1 and VCAM-1 were only basically expressed on HMC at very low levels in the control groups without stimulation. After stimulation by rhIL-1 beta or rhTNF alpha, however, their expression was markedly upregulated. The maximal mRNA expression level of ICAM-1 stimulated by rhTNF alpha was present at the 8th hour, but in the remaining groups the maximal mRNA expression levels of ICAM-1 or VCAM-1 were all present at the 4th hour. Compared with control groups, ICAM-1 protein expression was significantly increased from the 4th hour after rhIL-1 beta stimulation (P < 0.05), but in the remaining groups ICAM-1 or VCAM-1 protein expression was significantly raised from the 8th hour after stimulation (P < 0.001). CONCLUSION: These results suggest that upregulated expression of ICAM-1 and VCAM-1 by inflammatory cytokines IL-1 beta and TNF alpha may play a pathogenic role in glomerulonephritis.

Cells, Cultured↗

[Infarcts of rostral basilar artery territories clinicoradiological evaluation].

34 cases with infarcts of rostral basilar territory arteries, including posterior cerebral artery (PCA), rostral basilar artery (BA) and superior cerebellar artery (SCA) confirmed by CT and MRI were reported. The clinical manifestations might be divided into 3 groups according to the supplying artery: the cortical branch of PCA (21 cases), the perforated branch of PCA (22 cases) and the SCA (10 cases). However, combination was often seen. MRI is superior than CT in finding lesions of this region. The use of digital substraction angiograph, magnetic resonance angiography and transcranial Doppler in defining the site of vascular occlusion was discussed.

Adult↗

[Construction of Chinese genomic cosmid library].

A Chinese genomic library has been constructed using SuperCos1 cosmid vector. 6.09 x 10(5) clones were obtained with an everage insert size of 40 kb ranging from 32 to 45 kb, which cover approximately 8.12 fold human genomic DNA. DNA pools prepared from the total library were screened with 6 known markers distributed on different chromosomes, which all were tested positive.

Asian People↗

[Application of self-made electrolyte reagents in SYNCHRON EL-ISE].

Based on the principle of the Ion Selected Electrode dilution method (indirect), a complete set of reagents for determining Na, K, Cl and CO2 have been developed. Compared with original BECKMAN reagents being applied in the SYNCHRON EL-ISE analyzer, the self-made reagents may satisfy clinical requirements for precision and accuracy, and have a good correlation with original reagents: rNa = 0.998, rK = 0.999, rCl = 0.998, rCO2 = 0.889, and the CV% within and between batches are less than 3.3 and 5.7 respectively; the rate of recovery is 99%-105%. NO influence on the electrode has been found through observing electrode slopes and SPAN values.

Chlorides↗

[Study on pharmacological regulation of the peritoneal stomata and its computer image processing].

Pharmacological regulation of the peritoneal stomata was studied by using traditional Chinese medicine and a medical image processing system attached to SEM. The results showed that the numbers, diameters and distributive density of the peritoneal stomata were significantly increased (P < 0.05) in the groups of white atractylodes rhizome and the pilose asiabell root. However, the effect of astraglus root was not obvious in comparison with the controls (P > 0.05). This was for the first time to show the regulation of the peritoneal stomata by using traditional Chinese medicines. According to the mechanism of the peritoneal stomata and ascites drainage, white atractylodes rhizome and pilose asiabell root may exert an important action on ascites treatment.

Animals↗

[The effect of RU486 on contractility of rabbit oviduct smooth muscle].

An investigation on the effect of RU486 on isolated ovicluct smooth muscle contraction of pseudopregant rabbits was carried out by using the mechanical-electrical transducer of Galson recorder. The results showed that: (1) RU486 acted directly on the oviduct smooth muscle by increasing contractile frequency, without changing tension and amplitude. This effect is similar to that found in the in vivo experiment. (2) RU486 partially inhibited Ca(2+)-induced smooth muscle contraction and also showed significant synergistic effect of Verapamil and antagonistic effect of NE on muscle contractility. However, RU486 is unable to exert any effect on Forskolin-stimulated contraction. Thus it appears that the RU486 effect on oviduct smooth muscle contraction is a result of affecting intracellular free calium, due possibly to interference of Ca2+ influx and/or endoplasmic reticulum Ca2+ release and Ca(2+)-Ip3 transducing mechanism.

Abortifacient Agents, Steroidal↗

Increased apoptosis accompanies neoplastic development in the human colorectum.

A disturbance in the balance between cell proliferation and cell loss, or apoptosis, may underlie neoplastic development. Therefore, we determined spontaneous apoptotic and proliferative rates in normal, hyperplastic, adenomatous, and malignant colorectal epithelia. In paired sections, DNA strand breaks were detected using the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, and apoptotic cells were also identified in H&E-stained slides by morphological criteria. Cell proliferation, bcl-2, and p53 expression were analyzed using specific monoclonal antibodies. In normal mucosa, luminal epithelial cells demonstrated higher rates of apoptosis compared to cells in the proliferative zone. Neoplastic transformation was associated with a significant increase in rates of apoptosis and proliferation. However, apoptosis, but not proliferation, decreased at the adenoma-to-carcinoma transition coincident with expression of mutant p53. In carcinomas, both mutant p53 and bcl-2 protein levels were associated with attenuated apoptotic rates. In conclusion, apoptosis is an important regulator of growth in normal and neoplastic colorectal epithelia. Increased apoptosis and proliferation accompany neoplastic transformation, suggesting that an alteration in apoptotic rates is an important event in colorectal carcinogenesis. Furthermore, the imbalance in these processes found in carcinomas may facilitate tumor growth and progression.

Apoptosis↗

A population genetic test of selection at the molecular level.

The role of natural selection in molecular evolution has been inferred primarily by rejection of null hypotheses based on neutral theory, rather than by acceptance of specific predictions based on selection. In this report, a population genetic test of a specific prediction for selection on DNA polymorphism is presented. Pyrethroid insecticide use constitutes an experiment for which form of selection and molecular target (voltage-gated sodium channels) are both known. As predicted, differential pyrethroid selection on tobacco budworm populations generated significant geographic heterogeneity in sodium channel marker allele frequencies, compared with arbitrary loci.

Alleles↗

Selective inhibition of phosphatidylinositol 3-kinase by phosphatidic acid and related lipids.

Activation of phosphatidylinositol 3-kinase (PI 3-kinase) is necessary for stimulation of cell division and inhibition of apoptosis in several cell types. We report that a synthetic phosphonolipid, 4-(hexadecyloxy)-3-(S)-methoxybutyl phosphonic acid (PoA), as well as the naturally occurring lipids, phosphatidic acid and lyso-phosphatidic acid, are potent and specific inhibitors of PI 3-kinase. The IC50's for inhibition using phosphatidylinositol as substrate ranged from 10-20 microM. PoA is also the putative primary intracellular metabolite following phospholipase D hydrolysis of the anti-tumour ether lipid, 2'-(trimethylammonio) ethyl-4-(hexadecyloxy)-3-(S)-methoxybutanephosphonate. These results suggests that inhibition of PI 3-kinase following metabolic degradation of ether lipids by phospholipase D may contribute to the cytotoxicity of these compounds. The sensitivity of PI 3-kinase to PA and lyso-PA could imply cross-talk between the phospholipase D and PI 3-kinase signal transduction pathways in vivo.

Animals↗

Predictors of groin complications after balloon and new-device coronary intervention.

We reviewed the clinical course of 5,042 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) using balloons or new devices: (stent, laser, directional and rotational atherectomy). A vascular complication was defined as the formation of a groin hematoma, bleeding, pseudoaneurysm, fistula, or the need for surgical repair. Vascular complications occurred in 309 (6.1%) patients, and 117 (2.3%) required vascular repair; among these patients, surgery was performed for correction of an an arteriovenous fistula in 12%, repair of pseudoaneurysm in 72%, repair for expanding hematoma and femoral artery lacerations in 10%, and retroperitoneal bleeding in 6%. The correlates of vascular complications were older age (66.8 vs 62.1 years; p < 0.0001), female gender (43% vs 26%; p < 0.0001), increased weight (82.1 +/- 16.46 vs 78.0 +/- 16.6 kg; p < 0.001), higher systolic blood pressure (140 +/- 25 vs 134 +/- 20 mm Hg; p < 0.001), increased heparin dose during the procedure (14,352 +/- 3,879 vs 13,599 +/- 3,508 IU; p = 0.001), administration of heparin after the procedure (232 vs 2,985 patients; p < 0.0001) and intracoronary stenting (14.9% vs 3.5%; p < 0.0001). Fifteen patients of 214 (7.0%) who underwent stent implantation had surgical repair. Vascular complications were not related to the size of the arterial sheath (8.11 +/- 0.8 vs 8.8 +/- 0.7Fr; p = 0.11) and the use of devices other than stents (laser, atherectomy) did not increase the rate of vascular complications.

Aged↗

Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides activate monocytes/macrophages.

The observation that the major membrane immunogens of the spirochetal pathogens. Treponema pallidum and Borrelia burgdorferi are lipoproteins prompted studies to investigate macrophage activation by the 47-kDa lipoprotein of T. pallidum and the acylated outer surface protein A (OspA) of B. burgdorferi. Both lipoproteins induced the synthesis of biologically active TNF-alpha and chloramphenicol acetyltransferase in a murine macrophage cell line transfected with a chloramphenicol acetyltransferase reporter gene controlled by a TNF promoter (TB2 cells). Nonacylated forms of these polypeptides did not induce cell activation. Comparison between purified OspA and B. burgdorferi cellular lipids revealed that the former was the more potent inducer of TNF-alpha. Synthetic lipohexapeptides corresponding to the N-termini of the 47-kDa lipoprotein of T. pallidum and OspA also activated TB2 cells in a dose-dependent fashion, whereas the nonlipidated hexapeptides were without effect, further underscoring the importance of protein acylation to cell activation. Among several lines of evidence supporting that macrophage stimulation by LPS and lipopeptides proceeds via different mechanisms, the most notable was that lipopeptides activated peritoneal macrophages from LPS-nonresponsive C3H/HeJ mice. The potential for spirochetal lipoproteins to function as general macrophage activators was demonstrated by the ability of the synthetic analogues to induce IL-1 beta, IL-6, and IL-12, in addition to TNF, in murine and/or human macrophages. Our findings indicate that spirochetal lipoproteins may be important immunomodulators in syphilis and Lyme disease and that the synthetic lipopeptides will be useful surrogates for studying immune mechanisms operative in the two spirochetal diseases.

Acylation↗

Complement-mediated neurotoxicity is regulated by homologous restriction.

The ability of beta-amyloid peptides to activate the classical complement cascade and the presence of various complement proteins including the membrane attack complex (C5b-9) on dystrophic neurites in Alzheimer's disease brains, raises the possibility that the complement system may contribute to this neurodegenerative disorder. To address this issue, we have studied the effect of complement activation on nerve growth factor (NGF)-differentiated rat pheochromocytoma PC12 cells, and on retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells. Although incubation of both cell types with human serum resulted in activation of complement, as indicated by iC3b formation, only PC12 but not SH-SY5Y cells were killed by human serum treatment. In contrast, heat-inactivated serum (56 degrees C, 45 min) was not neurotoxic. On SH-SY5Y cells, both PCR amplification and immunocytochemistry demonstrated the presence of CD59, a glycosylphosphatidylinositol-anchored protein that restricts homologous complement activation by inhibiting the formation of the membrane attack complex. The presence of CD59 probably accounts for the inability of human complement to lyse the human cell lines. Indeed, removal of glycosylphosphatidylinositol (GPI)-anchored proteins with phosphatidylinositol-specific phospholipase C (PI-PLC) rendered SH-SY5Y cells vulnerable to complement attack and eventually led to serum-medicated cell death. Reconstituted C5b-9 was also toxic to both PC12 and PI-PLC-pretreated SH-SY5Y cells. These observations suggest that complement activation can cause neuronal cell death and that this process is regulated by homologous restriction.

Animals↗

Na+, K(+)-ATPase, glutathione, and hydroxyl free radicals in cadmium chloride-induced testicular toxicity in mice.

Cadmium chloride (CdCl2)-induced biochemical changes were characterized in male, CD-1 mouse testes. CdCl2 inhibited the testes microsomal Na+,K(+)-ATPase activity in vitro and in vivo. The inhibitory range was 30-50 microns and the concentration for half maximal inhibition (IC50 value) was 90 microns over 5 min preincubation. CdCl2 (2mg/kg/day, s.c.) for 2 days significantly inhibited testes Na+,K(+)-ATPase (near 90% inhibition). The content of testicular GSH and the ratio of reduced glutathione (GSH)/GSSG (oxidized glutathione) decreased in CdCl2-treated groups. Using salicylate as a trapping agent and high pressure liquid chromatography with electrochemical detection (LCED), we measured the OH production in vivo. 2,5-dihydroxybenzoic acid (2,5-DHBA) and 2,3-dihydroxybenzoic acid (2,3-DHBA) as indices of hydroxyl free radical formation significantly increased after 5 days CdCl2 exposure. Pretreatment with vitamin E (20 mg/kg, s.i.d., i.m., 7d) protected CdCl2-induced increase in OH. generation in testes. From this study, it was demonstrated that CdCl2 induced testicular toxicity could possibly be mediated by a significant increase in hydroxyl free radical formation and a reduction in GSH content and Na+,K(+)-ATPase activity. Vitamin E seems to prevent the CdCl2 induced increase in hydroxyl free radical generation.

Animals↗

Should the freehand allograft be abandoned as a reliable alternative for aortic valve replacement?

Cryopreserved aortic allografts were used for aortic valve replacement in 80 patients between 1986 and 1994 (infracoronary in 46 and complete root replacement in 34). Hospital mortality was 6.3% (5/80) with all deaths occurring in the infracoronary group. Three of five deaths were in patients with endocarditis and valve ring abscess. Left ventricular-aortic mean pressure gradients across the allograft valves were significantly lower for root replacement patients (mean, 9.0 +/- 6.9 mm Hg versus 18.1 +/- 8.7 mm Hg for infracoronary patients) (p = 0.0001). No patient having root allograft replacement had early echocardiographic aortic insufficiency greater than grade 1 versus 28% of those having infracoronary implantations. Late aortic insufficiency of grade 2 or greater was seen in 46% of patients having infracoronary implantation versus 17% of patients having root implantation. Nine patients had explantation of an aortic allograft (eight infracoronary and one root). Reasons for explantation were as follows: endocarditis (three infracoronary, one root), technical (three infracoronary), undiagnosed idiopathic hypertrophic subaortic stenosis (1 patient), and prolapsing infracoronary leaflet (1 patient). Actuarial freedom from grade 3 and 4 aortic insufficiency or explantation was 77% at 7 years for infracoronary implantations. We conclude that the infracoronary aortic allograft has an unacceptable frequency of late insufficiency and its use in this position should be abandoned. The substantial incidence of late endocarditis in the infracoronary (free-hand) aortic allograft was surprising.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗