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L Yao

Publications and source records attributed to L Yao.

At least 19 recordsLinked to original sources
PubMed2001

A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist.

IL-22 is an IL-10 homologue that binds to and signals through the class II cytokine receptor heterodimer IL-22RA1/CRF2-4. IL-22 is produced by T cells and induces the production of acute-phase reactants in vitro and in vivo, suggesting its involvement in inflammation. Here we report the identification of a class II cytokine receptor designated IL-22RA2 (IL-22 receptor-alpha 2) that appears to be a naturally expressed soluble receptor. IL-22RA2 shares amino acid sequence homology with IL-22RA1 (also known as IL-22R, zcytor11, and CRF2-9) and is physically adjacent to IL-20Ralpha and IFN-gammaR1 on chromosome 6q23.3-24.2. We demonstrate that IL-22RA2 binds specifically to IL-22 and neutralizes IL-22-induced proliferation of BaF3 cells expressing IL-22 receptor subunits. IL-22RA2 mRNA is highly expressed in placenta and spleen by Northern blotting. PCR analysis using RNA from various tissues and cell lines showed that IL-22RA2 was expressed in a range of tissues, including those in the digestive, female reproductive, and immune systems. In situ hybridization revealed the dominant cell types expressing IL-22RA2 were mononuclear cells and epithelium. Because IL-22 induces the expression of acute phase reactants, IL-22RA2 may play an important role as an IL-22 antagonist in the regulation of inflammatory responses.

Amino Acid Sequence↗
PubMed2001

Interleukin 20: discovery, receptor identification, and role in epidermal function.

A structural, profile-based algorithm was used to identify interleukin 20 (IL-20), a novel IL-10 homolog. Chromosomal localization of IL-20 led to the discovery of an IL-10 family cytokine cluster. Overexpression of IL-20 in transgenic (TG) mice causes neonatal lethality with skin abnormalities including aberrant epidermal differentiation. Recombinant IL-20 protein stimulates a signal transduction pathway through STAT3 in a keratinocyte cell line, demonstrating a direct action of this ligand. An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.

Animals↗
PubMed2001

Hyperinsulinemia superimposed on insulin resistance does not elevate blood pressure.

The role of hyperinsulinemia and insulin resistance in the development of hypertension is an area of much current interest. A central question that remains unanswered is whether exogenous hyperinsulinemia can elevate blood pressure (BP) in the presence of pre-existing insulin resistance. To examine this proposition, we studied the effects of chronic fructose feeding on plasma insulin levels and BP in insulin-resistant Zucker fatty rats and in lean (insulin-sensitive) controls. In addition, vascular responses to norepinephrine in aortae and mesenteric arteries were compared between groups. Zucker fatty rats were hyperinsulinemic, insulin-resistant, yet normotensive when compared with age-matched lean controls. Long term fructose feeding increased plasma insulin levels and BP in the lean group. Strikingly, the fatty rats remained refractory to fructose-induced increases in BP despite exaggeration of hyperinsulinemia. Vascular reactivity assessed in aortae and mesenteric arteries was comparable between groups. These data suggest that, in vivo, the mechanisms of hyperinsulinemia-induced hypertension are not operative in the face of pre-existing insulin resistance in obese Zucker rats.

Animals↗
PubMed2001

Identification of the ligand-binding domain of human vascular-endothelial-growth-factor receptor Flt-1.

The vascular-endothelial-growth-factor (VEGF) receptor Flt-1 has been shown to be involved in vasculogenesis and angiogenesis. The receptor is characterized by seven immunoglobulin-like loops within the extracellular domain and the first three N-terminal immunoglobulin-like loops are involved in high-affinity binding of VEGF. The minimal extracellular domains of Flt-1 to achieve VEGF binding were screened using the yeast two-hybrid system. The result showed that the binding capacity of loop2-3 was close to that of loop1-3. The two truncated mutants consisting of loop2-3 and loop1-3 were expressed in the methylotrophic yeast Pichia pastoris at high levels (0.3 g[corrected]/litre). The corresponding proteins, named soluble (s)Flt-1(2-3) and sFlt-1(1-3), were purified. An in vitro biological activity assay showed that the binding capacity of sFlt-1(2-3) to human VEGF(165) and the inhibiting effect of it on human umbilical-vein endothelial cell proliferation stimulated by human VEGF(165) were close to those of sFlt-1(1-3). Animal tests showed that sFlt-1(2-3) could significantly inhibit the formation of regenerated blood vessels stimulated by hVEGF(165).

Angiogenesis Inhibitors↗
PubMed2001

Isoflurane-induced protection against myocardial stunning is independent of adenosine 1 (A(1)) receptor in isolated rat heart.

Volatile anaesthetics can pharmacologically enhance the recovery of stunned myocardium, but the mechanism is still unknown. This study sought to determine whether isoflurane attenuates myocardial stunning, and whether the myocardial protection of isoflurane is mediated by adenosine A(1) receptors. Five groups (n=8) of isolated rat hearts were studied in the Langendorff apparatus. The control groups underwent 20-min ischaemia with or without adenosine receptor antagonist (DPCPX, A(1)()selective) treatment (Cont group and DPCPX group). In the isoflurane groups, isoflurane (1.5 MAC) was present throughout the experiment (Iso group) and DPCPX (200 nM) was administered from 10 min before ischaemia (Iso+DPCPX(pre-I) group) or the beginning of reperfusion (Iso+DPCPX(post-I) group) to the end of experiment. The isoflurane groups had a lower end-diastolic pressure than the control groups (P<0.05). Developed pressure recovered to 77, 76, and 82% in Iso, Iso+DPCPX(pre-I) and Iso+DPCPX(post-I) groups, respectively (P<0.05 compared with control groups). LV+dp/dt(max) recovered to 53, 86, 81, 84, and 60% of pre-ischaemic values in Cont, Iso, Iso+DPCPX(pre-I), Iso+DPCPX(post-I), and DPCPX groups. LV-dp/dt(min) recovered to 55, 84, 83, 81, and 62%, respectively. Both LV+dp/dt(max) and LV-dp/dt(min) were significantly different (P<0.05) between control and isoflurane groups during reperfusion. There were no significant differences among the isoflurane groups. Our data show that isoflurane enhances the post-ischaemic functional recovery of isolated rat heart and that block of A(1) receptors does not abolish the beneficial effects of isoflurane. We conclude that A(1)()receptors are not involved in isoflurane-induced myocardial protection in the isolated rat heart.

Anesthetics, Inhalation↗
PubMed2001

Ethanol acts synergistically with a D2 dopamine agonist to cause translocation of protein kinase C.

Ethanol and other drugs of abuse increase synaptic dopamine levels; however, little is known about how ethanol alters dopaminergic signaling. We have reported that ethanol induces translocation of delta and epsilon protein kinase C (PKC) in neural cells in culture. Using NG108-15 and Chinese hamster ovary cell lines that express the dopamine D2 receptor (D2R), we show here that the D2R agonist R(-)-2,10,11-trihydroxy-N-propyl-noraporphine hydrobromide (NPA) also causes translocation of delta and epsilon PKC to the same sites as ethanol-induced translocation. D2R agonist and ethanol-induced translocation of delta and epsilon PKC share a common pathway that is blocked by pertussis toxin and requires phospholipase C (PLC) activity. These data suggest that both D2R agonists and ethanol activate PLC via a trimeric G protein leading to production of diacylglycerol with subsequent activation and translocation of delta and epsilon PKC. Moreover, ethanol and NPA, when present together at low concentrations that alone are ineffective, act synergistically to cause translocation of delta and epsilon PKC. Our data suggest that ethanol causes translocation of delta and epsilon PKC but cells expressing the D2R, such as neurons in the nucleus accumbens, may be particularly sensitive to low concentrations of ethanol.

Alcoholism↗
PubMed2001

Endothelin antagonism uncovers insulin-mediated vasorelaxation in vitro and in vivo.

The endothelial actions of insulin remain an area of intense research because they relate to both insulin sensitivity and vascular tone. Physiological doses of insulin evoke endothelium-dependent vasorelaxation in humans; however, this remains a pharmacological phenomenon in rat aortas. Because insulin may stimulate the divergent production of both nitric oxide and endothelin-1, we hypothesized that the lack of insulin-induced vasorelaxation at low/subthreshold concentrations may be due to the concurrent production of endothelin-1, which in turn serves to inhibit nitric oxide-dependent, insulin-mediated dilation. To investigate this, we studied the effects of subthreshold concentrations of insulin (100 mU/L) on norepinephrine-induced contraction in rat aortas following short-term and long-term endothelin blockade. In addition, the effects of tetrahydrobiopterin inhibition (with diaminohydroxyprimidine) on norepinephrine-induced contraction in the presence of insulin and endothelin receptor blockade were investigated. Subthreshold concentrations of insulin failed to evoke vasorelaxation in rat aortas. Strikingly, short-term endothelin A/B receptor blockade with bosentan (10(-2) mmol/L) uncovered insulin-mediated dilation; the percent maximum contraction and sensitivity of aortas to norepinephrine were attenuated (% maximum relaxation: bosentan+insulin 74+/-4%* versus bosentan 92+/-3%, insulin 107+/-5% P:<0.002; pD(2) values: bosentan+insulin 6.87+/-0.14* versus bosentan 7.40+/-0.15, insulin 7.63+/-0.11, *P:<0.002). This effect was mediated through endothelin A receptors because bosentan and BQ-123 (10(-2) mmol/L) attenuated norepinephrine-induced contraction to a similar degree. In addition, insulin evoked vasorelaxation in aortas isolated from rats after long-term bosentan treatment (100 mg. kg(-1). d(-1), 3 weeks). The component of insulin-mediated vasorelaxation uncovered by endothelin receptor blockade was tetrahydrobiopterin-dependent because it was reversed by diaminohydroxyprimidine. These data demonstrate, for the first time, the functional interaction between insulin, endothelin-1, and tetrahydrobiopterin in modulating vascular tone in rat aortas in vitro and in vivo.

Acetylcholine↗
PubMed2001

Improvement of left ventricular diastolic dynamics in prediabetic stage of a type II diabetic rat model after troglitazone treatment.

Troglitazone, an oral antidiabetic agent, has hypoglycemic effects in insulin-resistant animal models and humans. This study was conducted to evaluate its effect on left ventricular diastolic dynamics of a spontaneous diabetic (DM) rat model. Twenty DM rats and 20 age-matched nonDM rats were used, and 10 of each group were treated with troglitazone as a 0.2% food admixture for 10 weeks. At 5 and 15 weeks of age, Doppler echocardiography and M-mode echocardiography were performed. Troglitazone treatment significantly improved the left ventricular diastolic dynamics of DM rats: deceleration time (msec) of early diastolic inflow decreased significantly (treated 52 +/- 3 vs untreated 64 +/- 5, p = 0.0002), and peak velocity of early transmitral inflow (cm/sec) increased significantly (treated 96 +/- 7 vs untreated 86 +/- 8, p = 0.0216). The data suggest that troglitazone improves left ventricular diastolic dynamics of a DM rat model at prediabetic stage.

Animals↗
PubMed2001

Acute effect of human cardiotrophin-1 on hemodynamic parameters in spontaneously hypertensive rats and Wistar Kyoto rats.

There is considerable evidence to indicate that humoral factors play an important role in the development of left ventricular hypertrophy. Cardiotrophin-1 (CT-1) is a cytokine that has been shown to induce cardiac hypertrophy in a dose-dependent manner. The aim of the present study was to investigate the acute effect of CT-1 on hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) and to study the relationship between the plasma concentration of CT-1 and its hemodynamic effect. Ten-week-old SHR and age-matched WKY were used. Blood pressure (BP), heart rate (HR) and plasma concentration of CT-1 were measured both before and for 60 min after intravenous bolus injection of human CT-1 (10 microg/kg). CT-1 injection significantly decreased BP and significantly increased HR in SHR and WKY. There were significant differences in BP and HR between the two groups at all time points after injection. The lowest BP, highest HR and maximal plasma concentrations of CT-1 were observed in both groups within 10 min after injection. However, after converting the values into the percentage change from their respective baselines, there were no significant differences between the two groups in BP or HR at any time point. There was also no significant difference between the two groups at any time point in the plasma concentration of CT-1. This study indicates that CT-1 decreases BP and increases HR in both SHR and WKY. The most obvious change occurred within 10 min after injection. However, there was no significant difference in the hypotensive effect of CT-1 on 10-week-old SHR and WKY.

Animals↗
PubMed2001

Interleukin-18 expression induced by Epstein-Barr virus-infected cells.

Human Epstein-Barr virus (EBV)-negative Burkitt lymphomas cells usually grow as malignant subcutaneous tumors in athymic mice, but these tumors regress when the Burkitt cells are injected in conjunction with EBV-positive lymphoblastoid cells or when the Burkitt cells are transfected with the EBV latent membrane protein-1 (LMP-1) gene. Tumor regression is mediated, in part, by murine interferon gamma (IFN-gamma) and the IFN-gamma-induced murine chemokine IFN-gamma-inducible protein-10 (IP-10). The mechanisms by which EBV-LMP-1 promotes the expression of IFN-gamma has remained unclear. Here we show that murine interleukin (IL)-18 was consistently expressed in regressing Burkitt tumors but was either expressed at low levels or absent from progressively growing Burkitt tumors. By immunohistochemical methods, IL-18 protein was visualized in regressing but not in progressively growing Burkitt tumors. In contrast, IL-12 p35 and IL-12 p40 were only rarely expressed in regressing Burkitt tumors. In splenocyte cultures, EBV-infected lymphoblastoid cells and LMP-1-transfected Burkitt cells promoted the expression of IL-18 but not the expression of IL-12 p35 and IL-12 p40. A neutralizing antibody directed at murine IL-18 reduced murine IP-10 expression induced by EBV-immortalized cells in splenocyte cultures. These results provide evidence for IL-18 expression in response to a viral latency protein and suggest that IL-18 may play an important role as an endogenous inducer of IFN-gamma expression, thereby contributing to tumor regression.

Animals↗
PubMed2001

Dopamine D2 receptor inhibition of adenylyl cyclase is abolished by acute ethanol but restored after chronic ethanol exposure (tolerance).

Dopamine D2 (D2) receptors seem to mediate reinforcing responses to addicting drugs. A stably transfected NG108-15 cell line expressing the long form of the rat brain D2 receptor (D2L) was used to determine how ethanol modifies D2 receptor coupling to adenylyl cyclase. Activation of D2L receptors by the D2 receptor-specific agonist R-(-)-2,10,11-trihydroxy-N-propylnorapomorphine hydrobromide (NPA) inhibits both basal and receptor-stimulated cAMP production in these cells. Ethanol added acutely prevents D2L receptor inhibition of cAMP production. After chronic exposure to ethanol, however, D2L receptor coupling to adenylyl cyclase becomes tolerant to rechallenge with ethanol, i.e., ethanol no longer inhibits D2L receptor coupling and NPA inhibition of cAMP production is restored. Acute ethanol does not change NPA binding to D2 receptor in cell membranes but abolishes guanosine-5'-O-(3-thio)triphosphate induction of a lower-affinity state; chronic ethanol is without effect. The protein kinase A (PKA) inhibitor adenosine 3',5' cyclic monophosphorothioate, Rp-isomer, prevents acute ethanol inhibition of D2L receptor coupling. In contrast, the PKA activator adenosine 3',5' cyclic monophosphorothioate, Sp-isomer, reverses chronic ethanol-induced tolerance of D2L receptor coupling, restoring coupling to an ethanol-sensitive state. These results suggest that D2L receptor coupling to adenylyl cyclase via G(i) develops tolerance to ethanol inhibition, which appears to be influenced by PKA activity.

Adenylyl Cyclase Inhibitors↗
PubMed2001

[NIES-90 microcystin producing algae strain genome library construction and one isolated gene analysis].

OBJECTIVE: To construct a plasmid microcystis genome library for microcystin (MC) pertaining gene family screening or microcystis strain specific gene screening. METHODS: Extracting genome DNA from MC producing strain NIES-90, then digesting DNA by HindIII and ligating to CIPase treated pUC18/HindIII fragment which later transformed to JM109. After checking the library by Xgal/Antibiotics plate, clones isolation, a few clones were sequenced and specific primers synthesized; finally, PCR was used to testify clone's NIES-90 strain specificity. RESULTS: Successfully constructed a NIES-90 genome plasmid library with following functions: a) cloning efficiency more than 95% by comparing the white/blue clones ratio in Xgal Plate; b) 200-700 bp average insert length with 3 x 10(5) independent clones by independent clones analysis; c) 10 times more coverage of original NIES-90 genome; d) strong strain specificity by cross PCR analysis of some clone's sequence in two different microcystis strains compared with FACHB-469. CONCLUSION: We successfully constructed a NIES-90 MC producing microcystis strain's genome plasmid library which could be used for screening MC pertaining gene family because of high strain specificity of some clones.

DNA, Plant↗
PubMed2001

Detection of p53 gene mutations in sputum samples and their implications in the early diagnosis of lung cancer in suspicious patients.

OBJECTIVES: To evaluate the value of detecting p53 gene point mutations in sputum samples and its validity and reliability as a surveillance index in the early diagnosis of lung cancer in suspicious patients. METHODS: Sputum samples were collected from 54 cases identified as lung cancer and 114 cases identified as pulmonary benign disease. The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was performed for the detection of point mutations at exons 5-8 of the p53 gene, and sputum smears were also used for each sample. RESULTS: The detected mutation rate of 55.56% (30/54) in the lung cancer group was significantly higher than that of 1.75% (2/114) in the control group (P < 0.001). In the lung cancer group, the sensitivity, specificity, and positive likelihood ratio (PLR) of p53 mutations as a diagnostic marker for lung cancer were 55.56%, 98.25% and 31.75%, respectively. Also, the detection rates were 35.19% (19/54) by smears and 55.56% (30/54) by PCR-SSCP-silver stain, respectively. The differences both in rate and consistency were statistically significant (P < 0.01 and P < 0.05, respectively). Moreover, statistical analysis showed no significant relations between p53 mutations and clinical parameters such as gender, smoking habits, histotypes and stages, but the detection rate of p53 mutations in older patients (> or = 60 years old) was significantly higher than that in younger patients (P = 0.02). One case with p53 mutations at exon 5 in the control group was confirmed to be squamous cell carcinoma after 4 years of follow-up. CONCLUSION: Detection of p53 gene alterations in sputum samples by PCR-SSCP-silver stain can be used as a follow-up surveillance index for the early diagnosis of lung cancer in suspicious patients.

Adult↗
PubMed2001

[Detection of p53 gene alteration in sputum sample and its implications in early diagnosis of lung cancer].

OBJECTIVES: To evaluate the value of detecting point mutation of p53 gene in sputum sample and its validity and reliability as a surveillance index in early diagnosis of lung cancer in suspicious patients. METHODS: Sputum samples were collected from 54 cases identified as lung cancer and 114 cases as pulmonary benign disease. The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was performed for detection of point mutation at exon 5 - 8 of p53 gene and sputum smear also used for each sample. RESULTS: A detection rate of 55.56% (30/54) in the lung cancer group is significantly higher than that of 1.75% (2/114) in the control (P < 0.001). In the lung cancer group, the sensitivity, specificity, and positive likelihood ratio of p53 alterations as a diagnostic marker of lung cancer were 55.56%, 98.25% and 31.75 respectively. Moreover, the detection rates were 35.19% (19/54) by smears and 55.56% (30/54) by PCR-SSCP-silver stain; both the difference and consistency were statistically significant (P < 0.01 and P < 0.05 respectively). Statistic analysis did not show any significant relation between p53 alteration and clinical parameters such as gender, smoking habits, histotypes and stages, but the detection rate of p53 alteration in older patients (>or=60 years old) was significantly higher than that in younger (P = 0.02). One case with p53 alteration at exon 5 in the control group was confirmed to be squamous carcinoma after 4 years of follow-up. CONCLUSION: Detection of p53 gene alteration in sputum sample by PCR-SSCP-silver stain can be used as a follow-up surveillance index for early diagnosis of lung cancer in suspicious patients.

Adult↗
PubMed2000

Unusual renal features of Lowe syndrome in a mildly affected boy.

The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, mental retardation, and renal tubular dysfunction. The gene responsible for OCRL was identified by positional cloning and encodes a lipid phosphatase, phosphatidylinositol 4,5, bisphosphate [PtdIns(4,5)P2]5-phosphatase, which localizes to the Golgi apparatus and is suspected to play a role in Golgi vesicular transport [Suchy et al., 1995]. In addition to the ocular and renal manifestations, most boys with OCRL have cognitive problems and maladaptive behaviors including tantrums and stereotypies. We report a boy with a history of congenital cataracts and mild developmental delay who was also found to have hematuria with proteinuria but minimal signs of renal tubular dysfunction. Subsequent renal biopsy was compatible with a diagnosis of a noncomplement fixating chronic glomerulonephritis. Despite the atypical renal findings, skin fibroblast analysis for PtdIns (4,5)P2 5-phosphatase was performed, and enzyme activity was low, consistent with the diagnosis of OCRL. Western blot analysis from cell lysates showed the ocrl protein was decreased in size and amount. Our report shows atypical renal features of OCRL in a mildly affected boy. The possibility of OCRL should be considered in boys with cataracts and glomerular disease, even in the absence of renal tubular defects and frank mental retardation usually associated with the syndrome. Am. J. Med. Genet. 95:461-466, 2000. Published Wiley-Liss, Inc.

Acidosis, Renal Tubular↗
PubMed2000

Human glioma cell BT325 expresses a proteinase that converts human plasminogen to kringle 1-5-containing fragments.

Angiostatin, a specific angiogenesis inhibitor, is an internal fragment of plasminogen, and can be generated in many systems mediated by different enzymes in vitro. The mechanism of angiostatin generation in vivo has not been well defined. Here we demonstrated that human glioma cell line BT325 can express an enzyme that can convert purified plasminogen to angiostatin-like fragments with molecular masses of 65, 60, and 58 kDa, respectively. These fragments have an identical N-terminal as KVYLS, which starts from Lys(98) of the plasminogen precusor. According to their molecular mass, the three fragments should comprise kringle domain 1 to kringle domain 5 (kringle 1-5). The proteolytic fragments obtained as above can inhibit the growth of bovine aortic endothelial (BAE) cells specifically. The proteolysis process can be completely inhibited by serine proteinase inhibitors, and partially inhibited by EDTA. The molecular weight of the peptide, which contains an enzymatic activity responsible for the proteolysis, was 13 kD determined by gel filtration and SDS-PAGE. The present data suggest that glioma cell BT325 can produce a novel proteinase to generate kringle 1-5 of plasminogen as an angiogenesis inhibitor.

Amino Acid Sequence↗