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C Xie

Publications and source records attributed to C Xie.

At least 19 recordsLinked to original sources
PubMed1999

Cholesterol accumulation in tissues of the Niemann-pick type C mouse is determined by the rate of lipoprotein-cholesterol uptake through the coated-pit pathway in each organ.

Niemann-Pick type C (NPC) disease is associated with the accumulation of unesterified cholesterol in nearly all tissues and with progressive neurodegeneration. A murine model of this disease, the NPC mouse, was used to determine whether this sequestered cholesterol represented sterol carried in low density lipoprotein (LDL) and chylomicrons (CMs) taken up into the tissues through the coated-pit pathway. By 7 weeks of age, the sterol pool in the NPC mice had increased from 2,165 to 5,669 mg/kg body weight because of the daily sequestration of 67 mg of cholesterol per kg in the various organs. This was 7-fold greater than the rate of accumulation in control mice. The rate of LDL clearance in the NPC mouse was normal (523 ml/day per kg) and accounted for the uptake of 78 mg/day per kg of cholesterol in LDL whereas 8 mg/day per kg was taken up from CMs. Deletion of the LDL receptor in NPC mice altered the concentration of unesterified cholesterol in every organ in a manner consistent with the changes also observed in the rate of LDL cholesterol uptake in those tissues. Similarly, altering the flow of cholesterol to the liver through the CM pathway changed the concentration of unesterified cholesterol in that organ. Together, these observations strongly support the conclusion that, in NPC disease, it is cholesterol carried in LDL and CMs that is sequestered in the tissues and not sterol that is newly synthesized and carried in high density lipoprotein.

Adrenal Glands↗
PubMed1999

Protection against amyloid beta peptide toxicity by zinc.

Zinc (Zn) is an essential element in normal development and biology, although it is toxic at high concentrations. Recent studies show that Zn at high concentrations accelerates aggregation of amyloid beta peptide (Abeta), the major component of senile plaques in Alzheimer's disease (AD). This study reports the effect of varying Zn concentrations on Abeta toxicity and the mechanism by which low concentrations function in a protective role. At Abeta/Zn molar ratios of 1:0.1 and 1:0.01, Zn produces significant protection against Abeta toxicity in cultured primary hippocampal neurons. At higher concentrations (1:1 molar ratio), Zn offers no protection or enhances Abeta toxicity. The protective effect of Zn against Abeta toxicity is due in part to the enhancement of Na+/K+ ATPase activity which prevents the disruption of calcium homeostasis and cell death associated with Abeta toxicity. Analysis of Na+/K+ ATPase activity in cultured rat cortical cells indicated that Zn exposure alone afforded a 20% increase in enzyme activity, although the differences were statistically insignificant. However, in cortical cultures exposed to a toxic dose of Abeta (50 microM), Zn at concentrations of 5 and 0.5 microM led to significant increases in Na+/K+ ATPase activity compared with levels in cells treated with Abeta alone. Zn at a 1:1 molar ratio (50 microM) led to a significant decrease in enzyme activity. Together, these data suggest that Zn functions as a double-edged sword, affording protection against Abeta at low concentrations and enhancing toxicity at high concentrations.

Amyloid beta-Peptides↗
PubMed1999

Curative external beam radiotherapy for prostate carcinoma: results in 231 patients treated in Lyon.

BACKGROUND: Radical prostatectomy and external beam radiation therapy (EBRT) are the mainstays of treatment of prostate cancer with curative intent. The possible development of radiation proctitis and rectal bleeding are major concerns when using EBRT. Recently, conformal radiotherapy has been introduced in an attempt to improve the results of EBRT. This paper presents an overview of the Lyon experience using standard EBRT with doses of 68 Gy, and reports the preliminary results of a study of conformal radiotherapy with dose escalation. METHODS: From 1981 to 1995, EBRT was used to treat 231 patients with localized adenocarcinomas of the prostate. The dose of EBRT was 68 Gy/34 fractions/7 weeks using a four-field box technique with 18-MeV photons. A feasibility study of conformal radiotherapy was commenced in 1996. To date, 145 patients have been treated with doses escalating from 68 to 80 Gy. RESULTS: In the EBRT group of 231 patients, the 5-year overall survival was 80.3%. Anorectal function was scored as excellent in 90% of patients. Rectal bleeding was seen in 14.3% of patients and required local treatment in only seven. In the group treated with conformal radiotherapy, the preliminary results indicate good early tolerance. CONCLUSION: The curative treatment of patients with prostate cancer using EBRT gives good long-term survival with low rectal toxicity. Conformal radiotherapy appears to be an interesting approach to improve local control and perhaps survival.

Adenocarcinoma↗
PubMed1999

Cholesterol balance and metabolism in mice with loss of function of Niemann-Pick C protein.

Type C Niemann-Pick disease is due to a mutation in Niemann-Pick C (NPC) protein, a putative determinant of intracellular cholesterol transport. This study quantifies cholesterol balance in vivo across all tissues in mice with this defect. Cholesterol balance in the heterozygous animal is normal, but in the homozygous mouse the whole animal cholesterol pool expands continuously from birth, reaching 5, 442 mg/kg at 7 wk. The size of this pool in each organ is proportional to the rate at which each tissue clears low-density lipoprotein-cholesterol. Despite this expansion, however, cholesterol synthesis is increased so that whole animal synthesis equals 180 mg. day-1. kg-1. Forcing additional cholesterol into the liver through the clathrin-coated pit pathway increases the hepatic cholesterol pool in control mice, all of which is esterified, while there is a much greater increase in this pool in mutant mice, all of which is unesterified. These findings are consistent with the view that there is a block in sterol movement from the lysosome to the sites of regulation in NPC disease and have important implications for understanding the function of the NPC protein in intracellular cholesterol metabolism, in general, and in the brain, in particular.

Animals↗
PubMed1999

Role of neutrophils and alpha1-antitrypsin in coal- and silica-induced connective tissue breakdown.

Mineral dusts produce emphysema, and administration of dust to rats results in the rapid appearance of desmosine and hydroxyproline in lavage fluid, confirming that dusts directly induce connective tissue breakdown. To examine the role of neutrophils and alpha1-antitrypsin (alpha1-AT) in this process, we instilled silica or coal into normal rats or rats that had been pretreated with antiserum against neutrophils. One day after dust exposure, lavage fluid neutrophils and desmosine and hydroxyproline levels were all elevated; treatment with antiserum against neutrophils reduced neutrophils by 75%, desmosine by 40-50%, and hydroxyproline by 25%. By 7 days, lavage fluid neutrophils and desmosine level had decreased, whereas macrophages and hydroxyproline level had increased. By ELISA analysis, lavage fluid alpha1-AT levels were increased four- to eightfold at both times. On Western blot, some of the alpha1-AT appeared as degraded fragments, and by HPLC analysis, 5-10% of the methionine residues were oxidized. At both times, lavage fluid exhibited considerably elevated serine elastase inhibitory capacity and also showed elevations in metalloelastase activity. We conclude that, in this model, connective tissue breakdown is initially driven largely by neutrophil-derived proteases and that markedly elevated levels of functional alpha1-AT do not prevent breakdown, thus providing in vivo support for the concept of quantum proteolysis proposed by Liou and Campbell (T. G. Liou and E. J. Campbell. Biochemistry 34: 16171-16177, 1995). Macrophage-derived proteases may be of increasing importance over time, especially in coal-treated animals.

Animals↗
PubMed1998

Glutathione transferase protects neuronal cultures against four hydroxynonenal toxicity.

Peroxidation of polyunsaturated fatty acids (PUFA), particularly arachidonic acid, leads to the generation of reactive aldehydes, including 4-hydroxynonenal (HNE). Recent studies have demonstrated an increase in lipid peroxidation, a decline in PUFA, as well as an increase in HNE, and a decrease in glutathione transferase (GST) in the brain in Alzheimer's disease. Four-hydroxynonenal is toxic to cultured neurons and to the brain of experimental animals. Although glutathione (GSH) has been shown to offer protection against HNE, no enzymatic system has been described which serves to detoxify these reactive species in neuronal cultures. Here, we describe the use of GST in the protection of neuronal cultures against HNE toxicity. Glutathione transferases are a superfamily of enzymes functioning to catalyze the nucleophilic attack of GSH on electrophilic groups on a second substrate. These enzymes function efficiently with 4-hydroxyalkenals, particularly HNE, as substrates. To investigate the protective effects of GST against HNE, primary hippocampal cultures were pretreated with GST before exposure to toxic doses of HNE which led to a statistically significant enhancement in cell survival. Pretreatment of cultures with equivalent levels of heat inactivated GST or antibody against GST did not offer protection against HNE. Control cultures pretreated with GST also demonstrated enhanced survival compared with control cells receiving no pretreatment. These data suggest that GST may be an important source of protection against the toxic effects of HNE.

4-Chloro-7-nitrobenzofurazan↗
PubMed1998

Serial observations after high dose talc slurry in the rabbit model for pleurodesis.

The mechanisms leading to a pleurodesis after the intrapleural injection of a sclerosing agent are not completely understood. The purpose of the present study was to make serial observations over 28 days on the pleural fluid findings and the gross and microscopic changes in the pleura after talc slurry administered intrapleurally at a high dose. Sixty-six rabbits received 400 mg/kg talc slurry. Ten to 12 rabbits were sacrificed 1, 2, 4, 7, 14, and 28 days after the intrapleural injection. At sacrifice the pleural fluid was measured and analyzed, and the pleural surfaces were studied grossly and microscopically. The intrapleural injection of 400 mg/kg talc slurry resulted in an acute exudative pleural effusion that persisted for 4 days. There was a progressive increase in the gross and microscopic fibrosis over the 28 days. Talc was present at the time of sacrifice in all animals. At 28 days there was a clinically significant pleurodesis in all rabbits; pleurodesis was not observed before this time. From this study we conclude that the intrapleural injection of 400 mg/kg talc slurry leads to an acute exudative pleural effusion and clinically significant pleurodesis that is present on day 28 but not day 14. It appears that the production of a pleurodesis requires higher doses of talc in rabbits without a chest tube than in humans with a chest tube.

Acute Disease↗
PubMed1998

In vivo time course of morphological changes and DNA degradation during the degeneration of castration-induced apoptotic prostate cells.

The in vivo time course of the morphological changes and DNA degradation in castration-induced apoptotic prostate cells was studied from the earliest to the latest stage of the degeneration process. To study this problem, we first induced apoptotic prostate cells in rats by castration for 3 days and then promptly and continuously blocked the death of healthy prostatic cells in the castrated rats by in vivo testosterone replacement. Because testosterone replacement could not stop the irreversible lysis of already damaged prostate cells, apoptotic cells at different stages of the degeneration process were eliminated sequentially from the prostate after the healthy prostate cells had been protected. Prostate cells at the earliest stage of apoptosis at the time when the castrated rats received testosterone replacement disappeared last. By tracing the morphological and DNA degradation of apoptotic cells after hormone treatment, we estimated the time course of prostate cell death from the early to the final stage. In the morphological evolution of apoptotic prostate cells, the clumping of nuclear chromatin, the degeneration of cytoplasm and the involution of the cell surface occurred and progressed simultaneously, resulting in the rapid formation of apoptotic bodies that were gradually digested by other cells. The DNA ladders of apoptotic cells were progressively cleaved into a mononucleosomal subunit that was further degraded at an additional site, generating a heterogeneous population of small nucleotides. The final digestion of DNA fragments occurred within the apoptotic bodies. The whole course of prostate cell death after castration took about 44 h.

Animals↗
PubMed1998

Reconstruction of the penis after severe injury.

Since 1986, five cases of one-stage reconstruction of the injured penis using microsurgical techniques have been successfully carried out. A piece of ilium based upon the deep circumflex iliac vessels is used to form the penis prop and a skin flap of the forearm is transferred to form the urethra and foreskin to encircle the prop. Then the vessels and nerves of the skin flap of the forearm are anastomosed with the vessels and nerves of the thigh. Postoperative follow-up showed the constructed penis to be satisfactory in contour, allow free flow of urine, provide cutaneous sensory recovery and satisfactory sexual function in four married patients. Radiography showed the bony structure of the penis prop to be normal. This method has advantages over the one-stage procedure in terms of contour, urinary flow, satisfactory sexual function and long-term benefits. Most of all it has solved the problem of poor blood supply into the reconstructed penis prop.

Adult↗
PubMed1998

Sib mating designs for mapping quantitative trait loci.

The power to separate the variance of a quantitative trait locus (QTL) from the polygenic variance is determined by the variability of genes identical by descent (IBD) at the QTL. This variability may increase with inbreeding. Selfing, the most extreme form of inbreeding, increases the variability of the IBD value shared by siblings, and thus has a higher efficiency for QTL mapping than random mating. In self-incompatible organisms, sib mating is the closest form of inbreeding. Similar to selfing, sib mating may also increase the power of QTL detection relative to random mating. In this study, we develop an IBD-based method under sib mating designs for QTL mapping. The efficiency of sib mating is then compared with random mating. Monte Carlo simulations show that sib mating designs notably increase the power for QTL detection. When power is intermediate, the power to detect a QTL using full-sib mating is, on average, 7% higher than under random mating. In addition, the IBD-based method proposed in this paper can be used to combine data from multiple families. As a result, the estimated QTL parameters can be applied to a wide statistical inference space relating to the entire reference population.

Animals↗
PubMed1998

Efficiency of multistage marker-assisted selection in the improvement of multiple quantitative traits.

The application of marker-assisted selection (MAS) to breeding programmes depends on its relative cost and the expected economic return compared to conventional phenotypic selection. The relative efficiency of MAS can be increased through a two-stage selection scheme or through marker-based, multiple-trait improvement. However, the effectiveness of these alternatives has not been quantified. In this study, we evaluate the efficiency of MAS relative to conventional phenotypic selection and marker-only selection in multistage selection for the improvement of multiple traits. We further incorporate the costs of obtaining measurements on phenotypic characters and marker loci into the objective function to evaluate the efficiency of MAS with respect to the gain per unit cost. Deterministic analyses indicate that excluding costs, multiple-trait MAS can be used to increase the aggregate breeding values in quantitative characters and is expected to be more effective than conventional selection or single-trait MAS. Two-stage MAS has a slightly reduced gain because of culling in the first stage. If the objective function is to maximize the gain per unit cost, multiple-trait MAS is inferior to phenotypic selection in most of the selection schemes investigated when the cost ratio (r) of obtaining measurements on phenotypic characters to scoring marker loci is less than unity (r < or = 1.0) and the heritability (h2) is greater than 0.3. The efficiency of MAS increases as r increases and h2 decreases. For MAS to be more effective, it is necessary to decrease further the cost associated with molecular marker assays.

Chromosome Mapping↗
PubMed1998

Identification of T cells that respond to serovar-specific regions of the Chlamydia trachomatis major outer membrane protein in persons with serovar E infection.

Protection from Chlamydia trachomatis infection is serovar-specific and T cell-dependent; however, the T cell epitopes identified to date have not been serovar-specific. The chlamydial major outer membrane protein (MOMP) contains serovar-specific B cell epitopes in four regions of the molecule whose amino acid sequence varies among serovars, the variable segments (VS). Serovar-specific T cell epitopes were sought by examining proliferation of blood mononuclear cells (PBMC) from Chlamydia-infected patients in response to VS peptides of serovar E MOMP. Serovar E-specific peptides from VS1, VS2, and VS4 stimulated PBMC to a greater extent in serovar E-infected than in non-E-infected subjects. Peptides containing constant regions of MOMP were recognized equally by all infected persons. The observed responses were attributable to T cells. T cell recognition of serovar-specific regions of MOMP is common and may contribute to the serovar-specific protection previously observed.

Amino Acid Sequence↗
PubMed1998

Combining different line crosses for mapping quantitative trait loci using the identical by descent-based variance component method.

Mapping quantitative trait loci (QTLs) is usually conducted with a single line cross. The power of such QTL mapping depends highly on the two parental lines. If the two lines are fixed for the same allele at a putative QTL, the QTL is undetectable. On the other hand, if a QTL is segregating in the line cross and is detected, the estimated variance of the QTL cannot be extrapolated beyond the statistical inference space of the two parental lines. To reduce the likelihood of missing a QTL and to increase the statistical inference space of the estimated QTL variance, we present a consensus QTL mapping strategy. We adopt the identical by descent (IBD)-based variance component method originally applied to human linkage analysis by combining multiple line crosses as independent families. We explore the properties of consensus QTL mapping and demonstrate the method with F2, backcross (BC), and full-sib (FS) families. In addition, we examine the effects of the QTL heritability, marker informativeness, QTL position, the number of families, and family size. We show that F2 families notably outperform BC and FS families in detecting a QTL. There is a substantial reduction in the standard deviation of the estimated QTL position and the separation of the QTL and polygenic variance. Finally, we show that the power to detect a QTL is greater when using a small number of large families than a large number of small families.

Chromosome Mapping↗
PubMed1998

Systemic corticosteroids decrease the effectiveness of talc pleurodesis.

Corticosteroids can inhibit the inflammatory process and the formation of fibrosis. The purpose of this study was to determine whether the concurrent use of steroids at the time of talc-slurry pleurodesis would influence the development of the pleurodesis. One group of rabbits received an intrapleural injection of talc (400 mg/kg) and an intramuscular injection of triamcinolone (0.8 mg/kg) 1 d before talc instillation and weekly thereafter, whereas a control group received only talc. Ten rabbits in each group were killed at 6 h and at 1, 2, 4, 7, 14, and 28 d after instillation. The mean volume of pleural fluid was significantly lower in the group receiving corticosteroids at 6 h through 4 d after talc slurry than in the other groups. The degree of pleural adhesion was significantly smaller in the group receiving corticosteroids from Day 2 through Day 28. At Day 28, all 10 rabbits that received talc only had a pleurodesis score of 3 or 4, whereas only four of the 10 rabbits that also received steroids had a pleurodesis score of 3 or 4. This study shows that the use of corticosteroids at the time of talc-slurry pleurodesis markedly decreases the inflammatory reaction to the talc, and essentially prevents a pleurodesis from developing.

Animals↗
PubMed1998

Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer's disease.

OBJECTIVE: To investigate the levels of glutathione transferase (GST), a protective enzyme against aldehydes, and especially 4-hydroxynonenal (HNE) in the brain and ventricular CSF of autopsied AD and normal control subjects. BACKGROUND: Studies have implicated increased levels of oxidative stress in the brain in the pathogenesis of AD. Decreased levels of polyunsaturated fatty acids and increased levels of markers of lipid peroxidation have been reported in the brain in AD, particularly in areas severely affected in the disease. HNE, one marker of lipid peroxidation, is neurotoxic in neuronal culture and in vivo and is elevated in AD brain and CSF. METHODS: We measured levels of GST activity and protein in multiple brain regions and ventricular CSF in short-postmortem-interval AD patients and age-matched prospectively evaluated control subjects. RESULTS: A decrease in GST activity in all brain areas was observed in AD compared with controls with significant decreases in the amygdala, hippocampus and parahippocampal gyrus, inferior parietal lobule, and nucleus basalis of Meynert. Levels of GST protein also were depleted in most brain regions in AD. A significant decrease in GST activity and protein levels was also found in ventricular CSF in AD. CONCLUSION: Reduced levels of GST, a protective mechanism against HNE, may have a role in the pathogenesis of neuron degeneration in AD.

Aged↗
PubMed1998

Comparisons of pleurodesis induced by talc with or without thymol iodide in rabbits.

STUDY OBJECTIVE: At the present time, talc administered either as a slurry or an aerosol is a popular agent for producing pleurodesis. Some investigators use iodized talc while others use plain talc. The purpose of the present study was to determine if iodized talc slurry produced a better pleurodesis in animals than did plain talc. DESIGN: New Zealand white male rabbits were randomly assigned to receive talc slurry, 200 mg/kg, with or without the addition of 50 mg iodide intrapleurally. Approximately 10 rabbits in each group were killed 1, 2, 4, 7, 14, and 28 days after the injection. The amount and character of pleural fluid, the degree of pleural adhesions, and the microscopic changes were compared in the two different groups. RESULTS: The pleural fluid findings, the gross adhesion score for the pleura, and the microscopic changes in the visceral pleura were essentially identical for the rabbits that received iodized talc and those that received plain talc. The injection of both plain talc and iodized talc produced a normoglycemic exudative pleural effusion that had, for the most part, disappeared by the fourth day postinjection. The amount of pleural fluid at 48 h was 3.3+/-0.6 mL in the plain talc and 2.2+/-0.5 mL in the iodized talc group. At 28 days, the mean degree of gross pleurodesis in the talc group was 2.6+/-0.2 compared with 2.3+/-0.2 in the iodized group, while the mean degree of microscopic fibrosis was 1.4+/-0.3 in the plain talc group compared with 2.0+/-0.3 in the iodized talc group. CONCLUSION: From this study, we conclude that the addition of 50 mg of iodide does not improve the results with talc slurry pleurodesis in rabbits.

Animals↗
PubMed1998

Effect of pneumothorax on pleurodesis induced with talc in rabbits.

OBJECTIVE: The purpose of this study was to determine if a small pneumothorax would influence the pleurodesis resulting from talc instillation. METHODS: Sixty rabbits received an intrapleural injection of 400 mg/kg talc slurry. One half also received 10 mL of air intrapleurally after the talc. Ten rabbits in each group were killed 2, 14, and 28 days after instillation. RESULTS: Two days after the injection, the mean volume of air in the animals that had received the air was 7.5+/-0.4 mL. There was no air present in any other rabbits. The volume of pleural fluid and the pleural fluid glucose, protein, cell count, and differential were similar in both groups on day 2, while the LDH level was significantly higher in the air group (p<0.05). The degree of gross adhesions and microscopic fibrosis was similar in both groups and increased with time. CONCLUSIONS: A small pneumothorax does not decrease the efficacy of talc pleurodesis in our experimental model. These results suggest that the presence of a small amount of intrapleural air is not a contraindication to talc pleurodesis in humans.

Animals↗