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Y Xu

Publications and source records attributed to Y Xu.

At least 685 records · Page 38Linked to original sources

A cluster of genes involved in polysaccharide biosynthesis from Enterococcus faecalis OG1RF.

Our previous work identified a cosmid clone containing a 43-kb insert from Enterococcus faecalis OG1RF that produced a nonprotein antigen in Escherichia coli. In the present work, we studied this clone in detail. Periodate treatment of lysates of the clone confirmed that the antigen was carbohydrate in nature. Analysis of DNA sequences and transposon insertion mutants suggested that the insert contained a multicistronic gene cluster. Database comparison showed that the cluster contained genes similar to genes involved in the biosynthesis of dTDP-rhamnose, glycosyltransferases, and ABC transporters involved in the export of sugar polymers from both gram-positive and gram-negative organisms. Insertions in several genes within the cluster abolished the immunoreactivity of the clone. This is the first report on a gene cluster of E. faecalis involved in the biosynthesis of an antigenic polysaccharide.

Antigens, Bacterial↗

Involvement of p53 and p21 in cellular defects and tumorigenesis in Atm-/- mice.

Disruption of the mouse Atm gene, whose human counterpart is consistently mutated in ataxia-telangiectasia (A-T) patients, creates an A-T mouse model exhibiting most of the A-T-related systematic and cellular defects. While ATM plays a major role in signaling the p53 response to DNA strand break damage, Atm-/- p53(-/-) mice develop lymphomas earlier than Atm-/- or p53(-/-) mice, indicating that mutations in these two genes lead to synergy in tumorigenesis. The cell cycle G1/S checkpoint is abolished in Atm-/- p53(-/-) mouse embryonic fibroblasts (MEFs) following gamma-irradiation, suggesting that the partial G1 cell cycle arrest in Atm-/- cells following gamma-irradiation is due to the residual p53 response in these cells. In addition, the Atm-/- p21(-/-) MEFs are more severely defective in their cell cycle G1 arrest following gamma-irradiation than Atm-/- and p21(-/-) MEFs. The Atm-/- MEFs exhibit multiple cellular proliferative defects in culture, and an increased constitutive level of p21 in these cells might account for these cellular proliferation defects. Consistent with this notion, Atm-/- p21(-/-) MEFs proliferate similarly to wild-type MEFs and exhibit no premature senescence. These cellular proliferative defects are also rescued in Atm-/- p53(-/-) MEFs and little p21 can be detected in these cells, indicating that the abnormal p21 protein level in Atm-/- cells is also p53 dependent and leads to the cellular proliferative defects in these cells. However, the p21 mRNA level in Atm-/- MEFs is lower than that in Atm+/+ MEFs, suggesting that the higher level of constitutive p21 protein in Atm-/- MEFs is likely due to increased stability of the p21 protein.

Animals↗

NF-kappaB inactivation converts a hepatocyte cell line TNF-alpha response from proliferation to apoptosis.

Toxins convert the hepatocellular response to tumor necrosis factor-alpha (TNF-alpha) stimulation from proliferation to cell death, suggesting that hepatotoxins somehow sensitize hepatocytes to TNF-alpha toxicity. Because nuclear factor-kappaB (NF-kappaB) activation confers resistance to TNF-alpha cytotoxicity in nonhepatic cells, the possibility that toxin-induced sensitization to TNF-alpha killing results from inhibition of NF-kappaB-dependent gene expression was examined in the RALA rat hepatocyte cell line sensitized to TNF-alpha cytotoxicity by actinomycin D (ActD). ActD did not affect TNF-alpha-induced hepatocyte NF-kappaB activation but decreased NF-kappaB-dependent gene expression. Expression of an IkappaB superrepressor rendered RALA hepatocytes sensitive to TNF-alpha-induced apoptosis in the absence of ActD. Apoptosis was blocked by caspase inhibitors, and TNF-alpha treatment led to activation of caspase-2, caspase-3, and caspase-8 only when NF-kappaB activation was blocked. Although apoptosis was blocked by the NF-kappaB-dependent factor nitric oxide (NO), inhibition of endogenous NO production did not sensitize cells to TNF-alpha-induced cytotoxicity. Thus NF-kappaB activation is the critical intracellular signal that determines whether TNF-alpha stimulates hepatocyte proliferation or apoptosis. Although exogenous NO blocks RALA hepatocyte TNF-alpha cytotoxicity, endogenous production of NO is not the mechanism by which NF-kappaB activation inhibits this death pathway.

Animals↗

beta-adrenergic stimulation induces transient imbalance between myocardial substrate uptake and metabolism in vivo.

At steady state, a balance is expected between net myocardial uptake of the principal exogenous carbon substrates and the rate at which these substrates are metabolized. Such a balance is present when the sum of the oxygen extraction ratios (OERs) for glucose, lactate, and free fatty acids (FFA) is near unity. We have previously observed that systemic administration of the beta-adrenergic agonist isoproterenol (Iso) induces a state of excess myocardial substrate uptake relative to the rate of substrate metabolism, reflected by a sum of OERs significantly >1.0. This occurs in conjunction with an Iso-stimulated increase in circulating insulin levels. The goal of the present study was to determine whether this excess substrate uptake depends on the effects of insulin and time. In open-chest anesthetized pigs, myocardial blood flow, substrate uptake, and oxygen consumption were measured at baseline and during systemic administration of Iso (0.08 microgram. kg-1. min-1 iv) under the following conditions: group 1 (n = 10), normal endogenous insulin release; group 2 (n = 10), inhibition of endogenous insulin release with somatostatin; group 3 (n = 7), at 45 and 90 min Iso; group 4 (n = 7), at 45 and 90 min Iso, with exogenous insulin given during the latter measurement. In group 1, plasma insulin rose fivefold with Iso while the sum of the OERs for glucose, lactate, and FFA increased from 0.92 +/- 0.21 at baseline to 1.57 +/- 0.17 with Iso (P < 0.01). In group 2, somatostatin blunted the increase in insulin with Iso and there was no significant change in the sum of OERs between baseline and Iso. In group 3, the sum of OERs increased from 0.95 +/- 0.11 at baseline to 1.69 +/- 0.20 at 45 min Iso (P < 0.01), similar to the response of group 1. However, the state of excess substrate uptake was transient; by 90 min Iso the sum of OERs declined to 0.69 +/- 0.21 (P < 0.05 vs. 45 min Iso). In group 4, excess substrate uptake could not be sustained at 90 min Iso despite administration of exogenous insulin. Systemic beta-adrenergic stimulation causes a transient condition of myocardial substrate uptake in excess of metabolism. Increased plasma insulin is necessary to produce this condition, but a high insulin level does not prolong the condition.

Adrenergic beta-Agonists↗

A reproducible model of circulatory arrest and remote resuscitation in rats for NMR investigation.

BACKGROUND AND PURPOSE: Because noninvasive physiological monitoring of cerebral blood flow, metabolic integrity, and brain ion and water homeostasis can now be accomplished with new, state-of-the-art MR spectroscopy and imaging techniques, it is appropriate to develop controllable and reproducible animal models that permit prolonged circulatory arrest and resuscitation in the magnet and also allow for studies of long-term survival and outcome. We have developed such a model in rats that involves minimal surgical preparations and can achieve resuscitation remotely within precisely controlled time. METHODS: Cardiac arrest was induced by asphyxiation, the duration of which ranged from 8 to 24 minutes. Resuscitation was achieved remotely by a slow, intra-aortic infusion of oxygenated blood (withdrawn either from the same rat before asphyxia or from a healthy donor rat) along with a resuscitation cocktail containing heparin (50 U/100 g), sodium bicarbonate (0.1 mEq/100 g), and epinephrine (4 micrograms/100 g). The body temperature was measured by a tympanic thermocouple probe and was controlled either by a heating pad (constant tympanic temperature = 37 degrees C) or by warm ambient air (constant air temperature = 37 degrees C). Interleaved 31P/1H nuclear magnetic resonance (NMR) spectroscopy was used in a selected group of rats to measure the cerebral metabolism before and during approximately 20 minutes of circulatory arrest and after resuscitation. RESULTS: The overall success rate of resuscitation, irrespective of the duration of cardiac arrest, was 82% (51 of 62). With a programmed infusion pump, the success rate was even higher (95%). The survival time for rats subjected to 15 and 19 minutes of asphyxia with core temperature tightly controlled was significantly lower than that with ambient temperature control (P < 0.001 and P < 0.04, respectively). High-quality NMR spectra can be obtained continuously without interference from the resuscitation effort. Final histological examinations taken 5 days after resuscitation showed typical neuronal damages, similar to those found in other global ischemia models. CONCLUSIONS: Because the no-flow time and resuscitation time can be precisely controlled, this outcome model is ideally suited for studies of ischemic and reperfusion injuries in the brain and possibly in other critical organs, permitting continuous assessment of long-term recovery and follow-up in the same animals.

Animals↗

Developmental regulation of the soluble form of insulin-like growth factor-II/mannose 6-phosphate receptor in human serum and amniotic fluid.

The insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-II/MPR) has a specific binding site for IGF-II, a fetal mitogen. In rodents, IGF-II/MPR expression declines dramatically after birth. To see whether such developmental regulation occurs in humans, we studied the ontogeny of the soluble form of IGF-II/MPR in amniotic fluid (AF) and serum. Phosphomannan-affinity purified AF IGF-II/ MPR was a single band of approximately 220 kDa, like the band in serum, and it bound IGF-II with affinity identical to that of the membrane-associated form. By quantitative immunoblot, the soluble IGF-II/MPR in serum and AF was found to undergo developmental regulation that parallels that of the rodent, although it is much less pronounced quantitatively. The highest levels are seen in midgestation, decreasing at term in both serum and AF. In serum, they further decline to one-third of the preterm levels by adulthood. As part of characterizing AF IGF-II binding, we also show that the prominent high-molecular mass IGF-II-binding protein in preterm AF is GPC3, a protein of the glypican family, recently cloned because its mutations predispose to Wilms' tumor. For the first time, we show that IGF-II binding to this protein is saturable, and therefore specific. These findings should promote understanding of the role of IGF-II and its binding proteins in human development.

Amniotic Fluid↗

Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease.

OBJECTIVES: To determine the annual rates of volumetric change of the hippocampus and temporal horn in cognitively normal elderly control subjects and individually matched patients with AD, and to test the hypothesis that these rates were different. BACKGROUND: Cross-sectional studies consistently reveal cerebral atrophy in elderly nondemented subjects compared with healthy young adults, and greater atrophy in patients with AD relative to elderly control subjects. However, rates of atrophy are estimated most accurately by performing serial measurements in the same individuals. METHODS: MRI-based volumetric measurements of the hippocampi and temporal horns were performed in 24 cognitively normal subjects aged 70 to 89 years who were individually matched with respect to gender and age with 24 patients with AD. Each subject underwent an MRI protocol twice, separated by 12 months or more. RESULTS: The mean annual rate of hippocampal volume loss among control subjects was -1.55+/-1.38% and the temporal horns increased in volume by 6.15+/-7.69% per year. These rates were significantly greater among AD patients: hippocampus, -3.98+/-1.92% per year, p < 0.001; temporal horn, 14.16+/-8.47% per year, p = 0.002. CONCLUSION: A statistically significant yearly decline in hippocampal volume and an increase in temporal horn volume was identified in elderly control subjects who represent typical aging individuals. These rates were approximately 2.5 times greater in patients with AD than in individually age- and gender-matched control subjects.

Aged↗

The role of oxidative stress in chemical carcinogenesis.

Oxidative stress results when the balance between the production of reactive oxygen species (ROS) overrides the antioxidant capability of the target cell; oxidative damage from the interaction of reactive oxygen with critical cellular macromolecules may occur. ROS may interact with and modify cellular protein, lipid, and DNA, which results in altered target cell function. The accumulation of oxidative damage has been implicated in both acute and chronic cell injury including possible participation in the formation of cancer. Acute oxidative injury may produce selective cell death and a compensatory increase in cell proliferation. This stimulus may result in the formation of newly initiated preneoplastic cells and/or enhance the selective clonal expansion of latent initiated preneoplastic cells. Similarly, sublethal acute oxidative injury may produce unrepaired DNA damage and result in the formation of new mutations and, potentially, new initiated cells. In contrast, sustained chronic oxidative injury may lead to a nonlethal modification of normal cellular growth control mechanisms. Cellular oxidative stress can modify intercellular communication, protein kinase activity, membrane structure and function, and gene expression, and result in modulation of cell growth. We examined the role of oxidative stress as a possible mechanism by which nongenotoxic carcinogens may function. In studies with the selective mouse liver carcinogen dieldrin, a species-specific and dose-dependent decrease in liver antioxidant concentrations with a concomitant increase in ROS formation and oxidative damage was seen. This increase in oxidative stress correlated with an increase in hepatocyte DNA synthesis. Antioxidant supplementation prevented the dieldrin-induced cellular changes. Our findings suggest that the effect of nongenotoxic carcinogens (if they function through oxidative mechanisms) may be amplified in rodents but not in primates because of rodents' greater sensitivity to ROS. These results and findings reported by others support a potential role for oxidative-induced injury in the cancer process specifically during the promotion stage.

Animals↗

An editing environment for DNA sequence analysis and annotation (extended abstract).

This paper presents a computer system for analyzing and annotating large-scale genomic sequences. The core of the system is a multiple-gene structure identification program, which predicts the most "probable" gene structures based on the given evidence, including pattern recognition, EST and protein homology information. A graphics-based user interface provides an environment which allows the user to interactively control the evidence to be used in the gene identification process. To overcome the computational bottleneck in the database similarity search used in the gene identification process, we have developed an effective way to partition a database into a set of sub-databases of "related" sequences, and reduced the search problem on a large database to a signature identification problem and a search problem on a much smaller sub-database. This reduces the number of sequences to be searched from N to O ([square root of] N) on average, and hence greatly reduces the search time, where N is the number of sequences in the original database. The system provides the user with the ability to facilitate and modify the analysis and modeling in real time.

Base Sequence↗

[Research on risk factors of 5 types of viral hepatities among population with high risk behaviors].

Epidemiological and serological survey on five types of viral hepatities (hepatitis A-hepatitis E) was conducted from October 1994 to December 1996 among 119 labourers returned from abroad, including 55 female prostitutes, 86 medical workers, 88 STD patients and 88 paid blood donors. HAV infection rates for all of the 5 groups were above 83%. HBV infection rate showed significantly different (chi 2 = 3.86, P < 0.05) between medical workers (53.49%) and the control group (30.43%). A significant difference (chi 2 = 5.36, P < 0.05) between HBV infection among prostitutes (52.73%) and control group (26.67%) was also noticed. In all the five groups, none was found to be anti-HDV positive. The HEV infection rates for the medical workers, prostitutes, blood donors, returned labourers and STD patients were 1.16%, 3.64%, 2.27%, 5.88% and 6.82%, whereas the anti-HCV positive rates were 1.16%, 3.64%, 0.00%, 0.00% and 1.14%, among them respectively.

Adult↗

Effects of different subtypes of histamine receptors on proliferation and differentiation of murine colony forming unit granulocyte-macrophage and colony forming unit megakaryocyte.

OBJECTIVE: To investigate the function and characteristics of histamine receptors on the hemopoietic progenitor cells. METHODS: BDF1 mice (both male and female), inbred at our university, aged 8-12 weeks, weighing 20-24 g, were used in this study. Bone marrow cells were incubated for 1 hour at 37 degrees C with 2-AT (H1 receptor agonist) or impromidine (H2 receptor agonist) alone, or in combination with the antagonists pyrilamine or cimetidine respectively. Control experiment was performed in Dulbecco's modified Eagle's Medium (DMEM) alone. Cells treated with different drugs were performed by colony forming unit-granulocyte-macrophage (CFU-GM) and colony forming unit-megakaryocyte (CFU-Meg) assay. RESULTS: When bone marrow cells were treated with 10(-8) mol/L to 10(-5) mol/L of 2-thiazolylethylamine (2-AT) which had no influence on CFU-GM and CFU-Meg proliferation, 10(-8) mol/L to 10(-5) mol/L of impromidine could increase the number of CFU-GM and CFU-Meg colonies. The effects of H2 receptor agonists on CFU-GM, CFU-Meg could be antagonized by H1 receptor agonist. CONCLUSIONS: Our findings suggest the existence of histamine H1 and H2 receptors on the hemopoietic progenitor cells and the antagonism between two different histamine receptor subtypes on the proliferation of CFU-GM and CFU-Meg.

Animals↗

Beneficial effects of early coronary reperfusion on left ventricular remodeling and systolic function in patients with acute myocardial infarction.

OBJECTIVE: To evaluate the beneficial effects of early coronary reperfusion on left ventricular remodeling (LVRM) and systolic function in patients with acute myocardial infarction (AMI). METHODS: Eighty-one patients with first AMI in the convalescent stage and having undergone left ventriculography (LVG) and coronary arteriography (CAG) were divided into four groups: the anterolateral wall (ALW) myocardial infarction (MI) non-reperfusion (n = 20) and reperfusion (n = 21), and inferoposterial wall (IPW) MI non-reperfusion (n = 20) and reperfusion (n = 20), according to infarct location and early treatment with or without successful coronary reperfusion therapy within 6 hours after onset of symptoms. By LVG, the parameters of LVRM and systolic function in the four MI groups were analyzed and compared with those in normal group (n = 25) and between the two reperfusion and non-reperfusion MI groups. RESULTS: In both ALW and IPW MI non-reperfusion groups, the left ventricular (LV) end-diastolic volume (EDV), circumference (EDC), short-axis dimension (EDD), short to long axis ratio (ED-D/L), sphericity index (ED-SI) and end-systolic volume (ESV) were all significantly increased (P < 0.01-0.001), while LV ejection fractions (LVEF) were significantly decreased (both P < 0.001) when compared with those of normal group; and the increase in ESV and decrease in LVEF were both significantly greater in ALW than in IPW MI groups (both P < 0.01). In both ALW and IPW MI reperfusion groups, however, the EDV, EDD, ESV, as well as the extent and severity of regional wall motion abnormality (RW-MA) were significantly smaller (P < 0.05-0.001), while LVEF were significantly higher (P < 0.01-0.001) when compared with those in the two non-reperfusion MI groups respectively. There were no longer significant differences in LVEF and ESV between ALW and IPW MI groups (both P > 0.05). The EDC in IPW MI reperfusion group and the ED-D/L and ED-SI in ALW MI reperfusion group were also significantly reduced compared with those in the two non-reperfusion MI groups respectively (P < 0.05-0.001). All the above parameters in the two reperfusion MI group were decreased to the normal in comparison with normal group except ESV and LVEF, and ED-D/L and ED-SI in IPW MI group. CONCLUSION: It was indicated that in both ALW and IPW MI non-reperfusion groups, LVRM had occurred in convalescent stage of AMI with an increase in EDV and EDC, spherical change in LV shape, and accompanying reduction in LV systolic function; and early coronary reperfusion in AMI could reduce the extent and severity of RWMA, prevent from LV enlargement and remodeling, and preserve or improve LV systolic function with more prominence in ALW MI.

Convalescence↗

Influence of recombinant retroviral vector expressing antisense TGF alpha on malignant phenotype of human pancreatic carcinoma cell line.

OBJECTIVE: To observe the effects of antisense TGF alpha on the growth of human pancreatic carcinoma cell line cells. METHODS: A recombinant retroviral vector expressing antisense TGF alpha was constructed, and transfected the ecotropic packaging cell line psi-2 with lipofectin. After the amphotropic packaging cell line PA317 was transfected with the virus supernatant of psi-2, the replication-defective, amphotropic retroviral supernatant was used to infect human pancreatic carcinoma cell line PC-7. Following puromycin selection, puromycin-resistant colonies were pooled and expanded to a cell line PC-7/AS-TGF alpha. RESULTS: The retroviral integration in the genomes of psi-2, PA317 and transformant PC-7 cells was confirmed by Southern blot hybridization. Northern blot hybridization showed a down regulation of endogenous TGF alpha in PC-7/AS-TGF alpha cell line. The high levels of growth inhibition and reduction of 3H-TdR incorporation in PC-7/AS-TGF alpha were evident. Also, the soft agar colony-formation and tumorigenicity in nude mice were significantly suppressed by antisense TGF alpha. CONCLUSION: The antisense TGF alpha expressing vector can block the target gene expression, suppress the cell growth and partially reverse the malignant phenotype of pancreatic carcinoma cells.

3T3 Cells↗

Diagnosis and treatment of acute central cervical cord injury.

OBJECTIVE: To clarify the diagnosis and management of acute central cervical cord injury. METHODS: Eighty-nine patients with acute cervical central cord injury were retrospectively reviewed. Sixty-three patients were treated conservatively and 26 were treated surgically. There were two acute deaths. Eighty-seven patients were followed up for 3 months to 15 years. RESULTS: Their average neurological score (ASIA) was increased from 41.7 at admission to 83.1 at follow-up. CONCLUSIONS: Acute central cervical cord injury should be differentiated from complete spinal cord injury, cervical myelopathy, cruciate paralysis and C8 nerve root injury. When compression of nerve tissue or cervical instability is identified, operative intervention should be indicated. The prognosis is less optimistic in the patients with severe primary injury and at old age.

Adult↗

CT-guided stereotactic biopsy of deep brain lesions: report of 310 cases.

OBJECTIVE: To evaluate the accuracy of CT-guided stereotactic biopsy in making correct pathological diagnosis and choosing corresponding management of brain tumors. METHODS: From 1991 to 1995, CT-guided stereotactic biopsy was performed in 310 patients with intracerebral lesions which were deep-seated or located in certain main functional areas. The patients were 198 men and 112 women. Their ages ranged from 4.5 to 70 years (average: 39.3 years). The lesions were located in the deep cerebrum (74 patients), the sellar area (62), the basal ganglion (51), the posterior part of the third ventricle (38), other intraventricleular area (21), the cerebellum (17) and the brain stem (9), and intracranial multiple lesions were found in 38 patients. RESULTS: Brain tumors were diagnosed pathologically in 266 patients (85.8%); inflammatory process in 25 (8.1%), other lesions in 8 (2.6%) and uncertain cases were 11 (3.6%). The overall positive rate of biopsy was 96.4% and the positive rate for brain tumor was 85.8%. Intracranial hematomas after biopsy were found in 5 patients (1.6%). There were no deaths induced by the biopsy or other serious complications. CONCLUSIONS: The results suggest that CT-guided stereotactic biopsy is a reliable method for histopathological diagnosis of brain tumors and it is also of great help in selecting appropriate management.

Adolescent↗

[Radioimmunoassay of substance P in human hypertrophic scar].

OBJECTIVE: To measure the content of substance P in human hypertrophic scar. METHOD: The method of radioimmunoassay was used to determine the content of substance P in human hypertrophic scar, non-hypertrophic scar and normal skin. RESULT: The content of substance P in hypertrophic scar was significantly higher than that in non-hypertrophic scar and normal skin (P < 0.01). CONCLUSION: Substance P may play an important role in the process of hypertrophic scar development.

Adolescent↗