Biomedical subjects

Jie Chen

Publications and source records attributed to Jie Chen.

At least 109 records · Page 6Linked to original sources

PubMed2005

Modulation of gene expression in MHCC97 cells by interferon alpha.

AIM: To elucidate the molecular mechanisms of the inhibitory effects of IFN-alpha on tumor growth and metastasis in MHCC97 xenografts. METHODS: Three thousand international units per milliliter of IFN-alpha-treated and -untreated MHCC97 cells were enrolled for gene expression analysis using cDNA microarray. The mRNA levels of several differentially expressed genes in cDNA microarray were further identified by Northern blot and RT-PCR. RESULTS: A total of 190 differentially expressed genes including 151 IFN-alpha-repressed and 39-stimulated genes or expressed sequence tags from 8,464 known human genes were found to be regulated by IFN-alpha in MHCC97. With a few exceptions, mRNA levels of the selected genes in RT-PCR and Northern blot were in good agreement with those in cDNA microarray. CONCLUSION: IFN-alpha might exert its complicated anti-tumor effects on MHCC97 xenografts by regulating the expression of functional genes involved in cell metabolism, proliferation, morphogenesis, angiogenesis, and signaling.

Carcinoma, Hepatocellular↗

PubMed2005

Cysteamine increases expression and activity of H+-K+-ATPase of gastric mucosal cells in weaning piglets.

AIM: To determine the in vivo and in vivo effects of cysteamine (CS) on expression and activity of H(+)-K(+)-ATPase of gastric mucosal cells in weaning piglets. METHODS: Eighteen litters of newborn Xinhuai piglets were employed in the in vivo experiment and allocated to control and treatment groups. From 12 d of age (D12), piglets in control group were fed basal diet, while the treatment group received basal diet supplemented with 120 mg/kg CS. Piglets were weaned on D35 in both groups. Six piglets from each group (n = 6) were slaughtered on D28 (one week before weaning), D35 (weaning), D36.5, D38, D42, and D45 (36 h, 72 h, one week and 10 d after weaning), respectively. Semi-quantitative RT-PCR was performed to determine the levels of H(+)-K(+)-ATPase mRNA in gastric mucosa. H(+)-K(+)-ATPase activity in gastric mucosa homogenate was also determined. Gastric mucosal epithelial cells from piglets through primary cultures were used to further elucidate the effect of CS on expression and activity of H(+)-K(+)-ATPase in vivo. Cells were treated for 20 h with 0.001, 0.01, and 0.1 mg/mL of CS (n = 4), respectively. The mRNA expression of H(+)-K(+)-ATPase and somatostatin (SS) as well as the H(+)-K(+)-ATPase activity were determined. RESULTS: in vivo, both mRNA expression and activity of H(+)-K(+)-ATPase in gastric mucosa of control group exhibited a trend to increase from D28 to D45, reaching a peak on D45, but did not show significant age differences. Furthermore, neither the mRNA expression nor the activity of H(+)-K(+)-ATPase was affected significantly by weaning. CS increased the mRNA expression of H(+)-K(+)-ATPase by 73%, 53%, 30% and 39% on D28 (P = 0.014), D35 (P = 0.017), D42 (P = 0.013) and D45 (P = 0.046), respectively. In accordance with the mRNA expression, H(+)-K(+)-ATPase activities were significantly higher in treatment group than in control group on D35 (P = 0.043) and D45 (P = 0.040). In vivo, CS exhibited a dose-dependent effect on mRNA expression and activity of H+-K+-ATPase. Both H(+)-K(+)-ATPase mRNA expression and activity in gastric mucosal epithelial cells were significantly elevated after 20 h of exposure to the moderate (H(+)-K(+)-ATPase expression: P=0.03; H(+)-K(+)-ATPase activity: P = 0.014) and high concentrations (H(+)-K(+)-ATPase expression: P=0.017; H(+)-K(+)-ATPase activity: P = 0.022) of CS. Significant increases in SS mRNA expression were observed to accompany the elevation of H(+)-K(+)-ATPase expression and activity induced by the moderate (P = 0.024) and high concentrations (P = 0.022) of CS. Low concentration of CS exerted no effects either on expression and activity of H(+)-K(+)-ATPase or on SS mRNA expression in cultured gastric mucosal epithelial cells. CONCLUSION: No significant changes are observed in mRNA expression and activity of H(+)-K(+)-ATPase in gastric mucosa of piglets around weaning from D28 to D45. CS increases expression and activity of gastric H(+)-K(+)-ATPase in vivo and in vivo. SS is involved in mediating the effect of CS on gastric H(+)-K(+)-ATPase expression and activity in weaning piglets.

Animals↗

PubMed2005

Chromosome 1q loss of heterozygosity frequently occurs in sporadic insulinomas and is associated with tumor malignancy.

The pathogenesis of sporadic insulinomas is not clear, and there are no reliable genetic determinants that are useful to distinguish malignant and benign forms of this tumor. It was reported that 1q LOH might contribute to pathogenesis in gastrinomas and was correlated with tumor progression. However, little data are available on 1q LOH in sporadic insulinomas. In our study, we determine whether 1q LOH occurs in sporadic insulinomas and is associated with tumor malignancy by performing 1q allelotyping with 17 markers in 40 tumors and pair normal DNA. Thirty-five (88%) insulinomas had 1q LOH. Of the 35 insulinomas with 1q LOH, 14 (40%) had 1q21.3-23.2 LOH over a 7.5 cM region (SRO-1), whereas LOH in 21 tumors (60%) occurred at 1q31.3 over an 11.4 cM area (SRO-2). Of 24 tumors without MEN1 LOH, 20 had either SRO-1 or SRO-2 LOH (83%), whereas in 16 tumors with MEN1 LOH, 9 were shown to have LOH at either SRO-1 or SRO-2 (56%) (p = 0.065). This result suggests that LOH at 2 SRO might be MEN1 gene independent and may contribute to the pathogenesis in a subset of insulinomas without MEN1 gene LOH. The presence of 1q21.3-23.2 LOH is significantly associated with malignancy of insulinomas (p = 0.014). The high frequency of LOH at 1q 21.3-23.2 and 1q31.3 suggests these 2 areas may harbor putative tumor suppressor genes that may play an important role in the tumorigenesis of a subset of insulinomas. LOH at 1q21.3-23.2, which was associated with tumor malignancy, could be one of the genetic markers for identifying malignancy in sporadic insulinomas.

Adolescent↗

PubMed2005

Distinct role of bilobalide and ginkgolide A in the modulation of rat CYP2B1 and CYP3A23 gene expression by Ginkgo biloba extract in cultured hepatocytes.

In the present study, primary cultures of rat hepatocytes were treated for 48 h with one of several extracts of Ginkgo biloba (10, 100, or 1000 microg/ml). Maximal increase in CYP2B1 and CYP3A23 mRNA levels was obtained at 100 microg/ml. This concentration of G. biloba extract also increased CYP3A2 and CYP3A18 mRNA expression in addition to CYP2B-mediated 7-benzyloxyresorufin O-dealkylation (BROD) and CYP3A-mediated testosterone 6beta-hydroxylation. In other experiments, cultured hepatocytes were treated for 48 h with bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, kaempferol, quercetin, isorhamnetin, or a flavonol diglycoside at a concentration that represented the level present in a 100 microg/ml concentration of an extract. Only bilobalide (2.8 microg/ml) increased CYP2B1 mRNA expression, and the -fold increase (7.9 +/- 0.5; mean +/- S.E.M.) was similar to that (8.3 +/- 1.7) by the extract. By comparison, only ginkgolide A (1.1 microg/ml) increased CYP3A23 mRNA expression, but the extent (2.6 +/- 0.5-fold) was less than the 5.3 +/- 1.7-fold increase by the extract. A greater concentration (5 microg/ml) of ginkgolide A was required to elevate CYP3A2 and CYP3A18 mRNA expression. Over the range of 1 to 5 microg/ml, bilobalide increased CYP2B1 mRNA and BROD, but not CYP3A23 mRNA or testosterone 6beta-hydroxylation, whereas ginkgolide A increased CYP3A23 mRNA and testosterone 6beta-hydroxylation, but not CYP2B1 mRNA or BROD. Overall, our novel results indicate a distinct role of bilobalide and ginkgolide A in the modulation of CYP2B1 and CYP3A23 gene expression and enzyme activities by G. biloba extract in primary cultures of rat hepatocytes.

Animals↗

PubMed2005

[Epidemiology of obesity and overweight and relation thereof to the prevalence of hypertension in 14 provinces/municipality in China].

OBJECTIVE: To investigate the current epidemiological characteristics of obesity and overweight in the middle-aged and elderly populations of china and to disclose their relation with such chronic diseases as hypertension. METHODS: A questionnaire survey and physical examination were conducted among the 35-85-years-old persons from 14 densely populated residential areas representative in economic development and medical conditions in 14 provinces/municipality in China (i.e., Henna, Hebei, Shandong, Shanxi, Guangdong, Jiangxi, Tianjin, Inner Mongolia, Shaanxi, Hunan, Hubei, Yunnan, Sichuan, and Zhejiang) where a large-scale epidemiological survey of atrial fibrillation were being conducted, one residential area for a province, selected by cluster sampling to investigate the health-related personal conditions and examine the blood pressure (BP), body height, weight, body mass index (BMI), etc. so as to understand the prevalence of overweight and obesity based on the diagnostic criteria of Chinese adults recommended by the Working Group on Obesity in China. RESULTS: 29056 persons, 13549 males with the average body height of 168 cm +/- 7 cm, average weight of 68 kg +/- 11 kg, and average body mass index (BMI) of 24 kg/m(2) +/- 3 kg/m(2), and 15507 females with the average body height of 156 cm +/- 6 cm, average weight of 60 kg +/- 10 kg, and average BMI of 24 kg/m(2) +/- 4 kg/m(2), were surveyed. The BMI of women was significantly higher than that of men (P = 0.005). The total prevalence of overweight in the 14 provinces/municipality was 38.93%, and the standardized prevalence of overweight was 37.17%, the total prevalence of obesity was 13.94%, and the standardized prevalence was 12.63%. The prevalence of obesity of men was 12.29%, significantly lower then that of women (15.39%, P < 0.001). The prevalence of overweight of men was 412.18%, significantly higher then that of women (36.97%, P < 0.001). The prevalence rates of obesity and overweight increased with age in the age group 35-64; and decreased with age in the age group 65 and over. In the men, the prevalence of overweight was the highest in the age group 45-54 (44.57%), and the prevalence of obesity was the highest in the age 55-64 (13.60%). In the women, the prevalence of overweight was the highest in the age group 55-64 (40.10%), and the prevalence of obesity was the highest in the age group 65-74 (19.97%). The prevalence of hypertension increased obviously with the BMI in these populations. CONCLUSION: Overweight and obesity are prevalent in China. Control of body weight is of great importance to the prevention and treatment of such chronic diseases as hypertension.

Adult↗

PubMed2005

Phylogenetic investigation of Dogiel's pericellular nests and Cajal's initial glomeruli in the dorsal root ganglion.

Cajal's initial glomeruli (IG) and Dogiel's pericellular nests (PCNs) were first described from methylene blue preparations of healthy animal tissues around the beginning of the last century. Since that time, although many reports have been published concerning these structures, few have focused on their development and phylogeny in healthy animals. The aim of this study was to examine the phylogenetic development of the sensory neurons in Cajal's IG (also called axonal glomeruli) and Dogiel's PCNs in the dorsal root ganglion (DRG) of the healthy adult frog, chick, rat, and rabbit. The three-dimensional architecture of the neurons was observed in ganglia by scanning electron microscopy after removal of the connective tissue. The neurons in the DRG of fish are known to be bipolar, but DRG neurons in the species examined here were found to be pseudounipolar, with single stem processes. The proportion of neurons having IG or PCNs increased with increasing phylogenetic complexity in the species examined here. Cajal's initial glomeruli, the convolution of the stem process near the parent cell body: In frogs, the ganglia were small and the neuronal stem processes were very short and straight. In chicks, the stem processes were longer; sometimes very long, tortuous processes were observed. However, no neurons with typical IG were observed in either species. Typical IG were observed in rats and rabbits; their occurrence was much more frequent in rabbits. Pseudounipolarization, i.e., the transition from bipolar to pseudounipolar neurons, is thought to save space, limit the length of neuronal processes, and reduce conduction time. However, an explanation of the evolutionary advantage of the IG, which is formed by the excessive prolongation of the stem process, remains elusive. The cytological and electrophysiological importance of IG has been discussed. Dogiel's pericellular nests (PCNs), which resemble balls of yarn made of thin unmyelinated nerve fibers around DRG neurons, have been observed in the DRG of rats and rabbits, but not in frogs or chicks. This interesting structure shows not only ontogenetic development in healthy animals but also phylogenetic development among species. The nerve fibers in the PCNs were less than 1.2 mum in diameter and had some varicosities. An immunohistochemical study using anti-tyrosine hydroxylase (TH) antibody revealed that some PCNs contain TH-positive nerve fibers and varicosities. Such TH-positive PCNs disappear after sympathectomy. These results suggest that the PCNs are made up of autonomic nerve fibers.

Animals↗

PubMed2005

Effect of Ginkgo biloba extract on procarcinogen-bioactivating human CYP1 enzymes: identification of isorhamnetin, kaempferol, and quercetin as potent inhibitors of CYP1B1.

In the present study, we investigated the effect of Ginkgo biloba extracts and some of its individual constituents on the catalytic activity of human cytochrome P450 enzymes CYP1B1, CYP1A1, and CYP1A2. G. biloba extract of known abundance of terpene trilactones and flavonol glycosides inhibited 7-ethoxyresorufin O-dealkylation catalyzed by human recombinant CYP1B1, CYP1A1, and CYP1A2, and human liver microsomes, with apparent Ki values of 2 +/- 0.3, 5 +/- 0.5, 16 +/- 1.4, and 39 +/- 1.2 microg/ml (mean +/- SE), respectively. In each case, the mode of inhibition was of the mixed type. Bilobalide, ginkgolides A, B, C, and J, quercetin 3-O-rutinoside, kaempferol 3-O-rutinoside, and isorhamentin 3-O-rutinoside were not responsible for the inhibition of CYP1 enzymes by G. biloba extract, as determined by experiments with these individual chemicals at the levels present in the extract. In contrast, the aglycones of quercetin, kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1 (apparent Ki = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent Ki = 418 +/- 50 nM). The mode of inhibition was competitive, noncompetitive, or mixed, depending on the enzyme and the flavonol. G. biloba extract also reduced benzo[a]pyrene hydroxylation, and the effect was greater with CYP1B1 than with CYP1A1 as the catalyst. Overall, our novel findings indicate that G. biloba extract and the flavonol aglycones isorhamnetin, kaempferol, and quercetin preferentially inhibit the in vitro catalytic activity of human CYP1B1.

Aryl Hydrocarbon Hydroxylases↗

PubMed2005

Development and application of a quantitative RT-PCR potency assay for a pentavalent rotavirus vaccine (RotaTeq).

A sensitive and reproducible method to determine the in vitro infectious potency of a pentavalent reassortant rotavirus vaccine (RotaTeq) has been developed as an alternative to classical potency assays. Potency was determined based on cell-based viral replication followed by quantitative reverse-transcription polymerase chain reaction (RT-QPCR) analysis. In the assay, confluent Vero cell monolayers in 96-well plates were inoculated with serial dilutions of test samples, a pentavalent reassortant rotavirus reference standard and assay controls, followed by incubation for 24h. The cells were lysed with a Triton X-100 solution and the lysates assayed by RT-QPCR to quantitate viral nucleic acid produced during replication. The RT-QPCR utilizes primer/probe sets specific to each virus reassortant and the potencies of each sample were determined relative to the reference standard. This assay, hereafter referred to as the Multivalent QPCR-Based Potency Assay (M-QPA), permits the specific quantitation of each individual reassortant virus in the presence of the other four reassortant viruses. In addition, the assay was demonstrated to be concordant with a traditional method (plaque assay) for the quantitation of infectious virus particles. It is anticipated that assays of this type will become a valuable tool in the assignment of potency values and in the monitoring of stability of live virus vaccines.

Animals↗

PubMed2005

NO-donating aspirin inhibits both the expression and catalytic activity of inducible nitric oxide synthase in HT-29 human colon cancer cells.

Nitric oxide-releasing aspirin (NO-ASA) is emerging as a potentially important chemopreventive agent against colon cancer. We examined in HT-29 human colon adenocarcinoma cells the effect of NO-ASA on the inducible form of nitric oxide synthase (NOS2), an enzyme implicated in colon carcinogenesis. NO-ASA inhibited in a time- and concentration-dependent manner the expression of NOS2 up to 70% compared to control (IC50 for this effect = 46 microM). NO-ASA also decreased the corresponding steady-state mRNA levels and this reduction preceded the reduction of protein levels by at least 6 h. NO-ASA also reduced the enzymatic activity of NOS2, as determined by a direct enzyme assay (maximal reduction = 80%) and by determining the accumulation of NO in the culture medium (IC50 for this effect = 36 microM). These effects of NO-ASA on NOS2 were paralleled by inhibition in cell growth (IC50 = 8.5 microM). These findings indicate that NO-ASA profoundly inhibits both the expression and enzymatic activity of NOS2 and suggest that these effects may represent an important mechanism for the colon cancer chemopreventive effect of NO-ASA.

Adenocarcinoma↗

PubMed2005

[Clinicopathologic features and surgical treatment of nonfunctioning islet cell tumors (78 case report)].

OBJECTIVE: To investigate surgical treatment results and clinical pathological specifics in the treatment of non-functional islet cell tumor. METHODS: To perform retrospective analysis of 78 cases of non-functional islet cell tumor treated at Peking Union Medical College Hospital from July 1968 through January 2005, and summarize clinical symptoms and signs, primary diagnosis before surgery, surgical treatment, pathologic specifics and immuno-histological analysis. RESULTS: Of 78 cases, 27 cases (34.6%) was found in physical examinations, the most common symptoms was upper abdominal pain and upper abdominal discomfort, 30.7% (24 cases) and 26.9% (21 cases) respectively; the most common sign being abdominal masses 35.9% (28 cases). B-us and CT are most commonly used forms of preoperative examination, with positive rates being 98.6% (71/72), 100% (53/53) respectively. Operative mortality was 1.28%, Radical surgery of malignant cases with 5 year survival rate 75% (9/12). Immuno-histological examinations showed that tumors with multi peptide linked hormones 78.6% (55/70), a larger number of positive examinations of neuron specific enolase and chromaffin, 91.4% (32/35) and 79.4% (27/34) respectively. Insulin, glucagon, pancreatic polypeptide, somatostatin, vasoactive intestinal peptide and gastrin positive rates are 64.6% (42/65), 47.5% (22/53), 45.8% (22/48), 37.5% (21/56), 23.9% (11/46) and 22.6% (7/31). CONCLUSIONS: Non-functional islet cell tumor lack specificity, Bus and CT are primary examination methods, immuno-histological analysis indicates various different hormones, but lacks the presence of related clinical symptoms. Surgery is an effective form of treatment in the treatment of non-functional islet cell tumor, even with distal metastasis, immediate surgical removal and treatment, extend prognosis.

Adenoma, Islet Cell↗

PubMed2005

Detecting normal cell radiosensitivity via assay of DNA damage in lymphocytes for individualizing radiotherapy in head and neck cancer patients.

PURPOSE: The purpose of this study was to determine whether the distribution of radiosensitivities in normal tissues of head and neck cancer patients, measured using a DNA damage assay on lymphocytes, is likely to provide sufficient discrimination to enable reliable identification of patients with abnormal sensitivities. MATERIAL AND METHODS: Radiosensitivity was assessed in 307 lymphocyte samples from unselected head and neck cancer patients and was quantified as the initial number of DNA double-strand breaks (dsb) induced per Gray and per DNA unit (200 Mbp). RESULTS: The existence of an inter-individual variation in the radiosensitivity parameter is described by the range (0.41--9.38 dsb/Gy/DNA unit) of the values found. We detected 37 patients who developed severe skin reactions during radiotherapy treatment and we compared their radiosensitivity values with the remaining patients treated. Radiosensitivity values of >7.20 dsb/Gy/DNA unit should theoretically correspond to highly radiosensitive patients. CONCLUSIONS: Our results suggest that initial DNA damage measured on lymphocytes offers an approach to predict the acute response of human normal tissues prior to radiotherapy. .

DNA Damage↗

PubMed2005

Time courses of B7 family molecules expressed on activated T-cells and their biological significance.

B7 family molecules are mainly expressed on the outer membrane of antigen-presenting cells. Here, our results demonstrate that CD80, CD86, and PD-L1 molecules are also expressed on T-cells that have been activated by simultaneous exposure to anti-CD3 and anti-CD28 mAbs, but PD-L2 and GL50 molecules were not detectable during the first six days of culture that follow such stimulation. We have analysed the time course of B7 family molecule expression on activated T-cells. CD28 and its ligands, CD80/CD86, have a high degree of co-localization and exhibit compartmental distribution on the membrane of activated T-cells, which is visualized by confocal microscopy. Interestingly, the co-localization of PD-1 and its ligand also exhibit similar phenomenon. Additionally, we provide evidence indicating that the CD80, CD86, and PD-L1 molecules are functional, since T-cells expressing B7 family molecules are able to stimulate the proliferation of highly purified allogeneic or autologous T-cells. Anti-CD80, anti-CD86, and soluble CD28-Ig protein could significantly attenuate the proliferation of T-cells, whereas anti-PD-L1 mAb may lead to the expansion of activated T-cells. We can conclude that activated T-cells expressing B7 family molecules could act as "APC" to trigger purified T-cells, and B7 family molecules play important roles during the activation of T-cells. These results indicate a need for further work, exploring the regulatory roles these molecules may play in immune responses.

Animals↗

PubMed2005

Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1.

The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector.

Animals↗

PubMed2005

Gene expression in rats with Barrett's esophagus and esophageal adenocarcinoma induced by gastroduodenoesophageal reflux.

AIM: To study the different gene expression profiles in rats with Barrett's esophagus (BE) and esophageal adenocarcinoma (EA) induced by gastro-duodeno-esophageal reflux. METHODS: Esophagoduodenostomy was performed in 8-wk old Sprague-Dawley rats to induce gastro-duodeno-esophageal reflux, and a group of rats that received sham operation served as control. Esophageal epithelial pathological tissues were dissected and frozen in liquid nitrogen immediately. The expression profiles of 4096 genes in EA and BE tissues were compared to normal esophagus epithelium in normal control (NC) by cDNA microarray. RESULTS: Four hundred and forty-eight genes in BE were more than three times different from those in NC, including 312 upregulated and 136 downregulated genes. Three hundred and seventy-seven genes in EA were more than three times different from those in NC, including 255 upregulated and 142 downregulated genes. Compared to BE, there were 122 upregulated and 156 downregulated genes in EA. In the present study, the interested genes were those involved in carcinogenesis. Among them, the upregulated genes included cathepsin C, aminopeptidase M, arachidonic acid epoxygenase, tryptophan-2,3-dioxygenase, ubiquitin-conjugating enzyme, cyclic GMP-stimulated phosphodiesterase, tissue inhibitor of metalloproteinase-1, betaine-homocysteine methyltransferase, lysozyme, complement 4b binding protein, complement 9 protein, insulin-like growth factor binding protein, UDP-glucuronosyltransferase, tissue inhibitor of metalloproteinase-3, aldolase B, retinoid X receptor gamma, carboxylesterase and testicular cell adhesion molecule 1. The downregulated genes included glutathione synthetase, lecithin-cholesterol acyltransferase, p55CDC, heart fatty acid binding protein, cell adhesion regulator and endothelial cell selectin ligand. CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux may develop into BE and even EA gradually. The gene expression level is different between EA and BE, and may be related to the occurrence and progression of EA.

Adenocarcinoma↗

PubMed2005

Non-Newtonian effects of blood flow on hemodynamics in distal vascular graft anastomoses.

Non-Newtonian fluid flow in a stenosed coronary bypass is investigated numerically using the Carreau-Yasuda model for the shear thinning behavior of the blood. End-to-side coronary bypass anastomosis is considered in a simplified model geometry where the host coronary artery has a 75% severity stenosis. Different locations of the bypass graft to the stenosis and different flow rates in the graft and in the host artery are studied. Particular attention is given to the non-Newtonian effect of the blood on the primary and secondary flow patterns in the host coronary artery and the wall shear stress (WSS) distribution there. Interaction between the jet flow from the stenosed artery and the flow from the graft is simulated by solving the three-dimensional Navier-Stokes equation coupled with the non-Newtonian constitutive model. Results for the non-Newtonian flow, the Newtonian flow and the rescaled Newtonian flow are presented. Significant differences in axial velocity profiles, secondary flow streamlines and WSS between the non-Newtonian and Newtonian fluid flows are revealed. However, reasonable agreement between the non-Newtonian and the rescaled Newtonian flows is found. Results from this study support the view that the residual flow in a partially occluded coronary artery interacts with flow in the bypass graft and may have significant hemodynamic effects in the host vessel downstream of the graft. Non-Newtonian property of the blood alters the flow pattern and WSS distribution and is an important factor to be considered in simulating hemodynamic effects of blood flow in arterial bypass grafts.

Anastomosis, Surgical↗

PubMed2005

Estrogen-induced abnormally high cystic fibrosis transmembrane conductance regulator expression results in ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) remains one of the most life-threatening and potentially fatal complications of assisted reproduction treatments, arising from excessive stimulation of the ovaries by exogenous gonadotropins administrated during in vitro fertilization procedures, which is characterized by massive fluid shift and accumulation in the peritoneal cavity and other organs, including the lungs and the reproductive tract. The pathogenesis of OHSS remains obscure, and no definitive treatments are currently available. Using RT-PCR, Western blot, and electrophysiological techniques we show that cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel expressed in many epithelia, is involved in the pathogenesis of OHSS. Upon ovarian hyperstimulation, rats develop OHSS symptoms, with up-regulated CFTR expression and enhanced CFTR channel activity, which can also be mimicked by administration of estrogen, but not progesterone, alone in ovariectomized rats. Administration of progesterone that suppresses CFTR expression or antiserum against CFTR to OHSS animals results in alleviation of the symptoms. Furthermore, ovarian hyperstimulation does not induce detectable OHSS symptoms in CFTR mutant mice. These findings confirm a critical role of CFTR in the pathogenesis of OHSS and may provide grounds for better assisted reproduction treatment strategy to reduce the risk of OHSS and improve in vitro fertilization outcome.

Animals↗

PubMed2005

Mammalian target of rapamycin (mTOR) signaling is required for a late-stage fusion process during skeletal myotube maturation.

Skeletal myogenesis is a well orchestrated cascade of events regulated by multiple signaling pathways, one of which is recently characterized by its sensitivity to the bacterial macrolide rapamycin. Previously we reported that the mammalian target of rapamycin (mTOR) regulates the initiation of the differentiation program in mouse C2C12 myoblasts by controlling the expression of insulin-like growth factor-II in a kinase-independent manner. Here we provide experimental evidence suggesting that a different mode of mTOR signaling regulates skeletal myogenesis at a later stage. In the absence of endogenous mTOR function in C2C12 cells treated with rapamycin, a kinase-inactive mTOR fully supports myogenin expression, but causes a delay in contractile protein expression. Myoblasts fuse to form nascent myotubes in the absence of kinase-active mTOR, whereas the formation of mature myotubes by further fusion requires the catalytic activity of mTOR. Therefore, the two stages of myocyte fusion are molecularly separable at the level of mTOR signaling. In addition, our data suggest that a factor secreted into the culture medium is responsible for mediating the function of mTOR in regulating the late-stage fusion leading to mature myotubes. Furthermore, taking advantage of the unique features of cells stably expressing a mutant mTOR, we have performed cDNA microarray analysis to compare global gene expression profiles between mature and nascent myotubes, the results of which have implicated classes of genes and revealed candidate regulators in myotube maturation or functions of mature myotubes.

Animals↗

PubMed2005

Morphologic study on levator ani muscle in patients with pelvic organ prolapse and stress urinary incontinence.

The objective of this study was to determine the morphologic changes of the levator ani muscle of patients with pelvic organ prolapse and stress urinary incontinence. Histological and histochemical analyses of the biopsy specimens of the levator ani muscle obtained from patients with stress urinary incontinence (SUI), pelvic organ prolapse (POP), and a control group were performed. The striated muscle-positive biopsy rate was 26.7% in the SUI group, 15.8% in the POP group, whereas it was 100% in the control group. The diameters of types I and II fibers decreased significantly with age and menopausal time in the control group. Splitting or fragmentation of fibers with red granules, which are called ragged-red fibers, were found in the SUI group. The diameters of levator ani muscle fibers in the control group were significantly larger than those in the SUI group (p=0.034<0.05). The degenerative change in histology and decrease in relative number of levator ani muscle might be associated with women suffering from SUI.

Adult↗