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Biomedical subjects

C Xie

Publications and source records attributed to C Xie.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

[Study on the reversal of cancer multidrug resistance by Chinese medicine Fw13-te41 in nude mice].

We have reported that three reversal agents were sifted out from 32 Chinese galenicals through a series of cell culture tests. Among them, Fw13-te41 has the best effect of reversal cancer multidrug resistance (MDR) in vitro. In this study, the reversal action of Fw13-te41 in vivo was studied on the animal model of nude mice with human leukemia k562/ADR. Twenty SPF BALB/c-nu/nu nude mice with xenograft tumor were randomly divided into the control group (n = 6), VCR group [intraperitoneal (i.p.) VCR 250 micrograms/week, n = 5], VCR + Fw13-te41 group (i.p VCR 250 micrograms/week + Fw13-te41 0.2 ml/day, equivalent to crude drug 10 g/kg, n = 5), and Fw13-te41 group (i.p Fw13-te41 0.2 ml/day, equivalent to crude drug 10 g/kg, n = 4). After 18 days, the rate of tumor inhibition (RTI) of VCR group was 19.79%, but the RTI of VCR + Fw13-te41 group was as high as 86.95% (P < 0.05). There results demonstrate that the Chinese medicine Fw13-te41 has an evident reversal action of malignancy MDR in vitro and in vivo.

Animals↗

Immunological studies on the cellular phenotype involved in corneal allograft rejection.

OBJECTIVE: To investigate the cellular phenotype involved in corneal allograft rejection using wholemounts analysis. METHODS: Corneal transplantation was performed between Sprague Dawley (SD) and Wistar rats. Corneal wholemounts were prepared from control rats and those after corneal transplantation on day 7 and 12. Immunohistochemical stain was performed on these wholemounts using monoclonal antibodies to transforming growth factor beta 1(TGF-beta 1), CD3, CD4, CD8, B lymphocytes, macrophages, dendritic cells and major histocompatibility complex (MHC) class II antigen. RESULTS: Corneal allograft rejection started on day 7 and reached its maximum from 10 to 14 days after corneal transplantation. Presence of TGF-beta 1-, CD3-, CD4-, CD8-, MHC class II-positive cells, macrophages and dendritic cells were noted at the limbus of both SD rats and Wistar rats. No positive cell was present in the central cornea of normal rats. All positive cells but B lymphocyte were noted in large numbers in the cornea after corneal allograft transplantation. Marked staining for TGF-beta 1 was noted during graft rejection. CONCLUSION: The corneal wholemounts technique provides a good visualization for the cellular phenotype involved in corneal allograft rejection. A variety of cells including TGF-beta 1, CD3, CD4, CD8, MHC class II antigen positive cells, macrophages and dendritic cells are involved in corneal allograft rejection. TGF-beta 1-positive cell might be an important immunosuppressive factor after corneal transplantation and also involved in the induction of fibrosis.

Animals↗

[Effect of pneumothorax on membrane diffusing capacity and pulmonary capillary blood volume].

OBJECTIVE: Investigating the effect of pulmonary membrane diffusing capacity(Dm) and pulmonary capillary blood volume(Vc) on carbon monoxide diffusing capacity (DLCO) in patients with pneumothorax before and after treatment, and clarifying the mechanism of hypoxemia due to pulmonary reexpansion. METHODS: Pulmonary function test, DLCO, Dm, Vc and arterial blood gas analysis were determined in 21 cases of pneumothorax before treatment and one week after pulmonary reexpansion. RESULTS: DLCO, Dm, Vc, partial pressure of arterial oxygen (PaO2), alveolar ventilation volume (VA), percentage of forced expiratory volume in one second to predicted value, and the ratio of dead space ventilation (VD) to tidal volume (VT) [VD/VT] were (64 +/- 4)%, (66 +/- 5)%, (70 +/- 5)%, (83.7 +/- 2.3) mm Hg, (4.4 +/- 0.2) L, (59 +/- 4)%, 0.340 +/- 0.020 respectively before treatment. After pulmonary reexpansion, they respectively were (71 +/- 4)%, (74 +/- 4)%, (80 +/- 6)%, (89.4 +/- 1.5) mm Hg, (5.40 +/- 0.20) L, (79 +/- 4)%, 0.210 +/- 0.010. They were significantly improved after treatment. Except for Dm, they were statistically different. Between Dm, Vc and DLCO, significant positive correlations were found during pneumothorax and one week after pulmonary reexpansion, especially correlation between Dm and DLCO was more apparent. Between Dm and DLCO significant positive correlations (r2 = 0.862, P < 0.0001; r2 = 0.728, P < 0.001) were found in study patients before and after treatment. So were Vc and DLCO (r1 = 0.643, P < 0.01; r2 = 0.52, P < 0.05). The correlation coefficient of Dm was markedly larger than Vc. CONCLUSIONS: The decrease in pulmonary diffusing function is related to Dm and Vc during pneumothorax, while decrease of Dm plays a major role. The hypoxemia is still presented in a period of time after pulmonary reexpansion, which is not related to VA and abnormality of ventilation-perfusion ratio (V/Q). It is chiefly due to unrecovery of Dm.

Adolescent↗

[Establishment of a heterologous graft model for human breast infiltrating duct carcinoma in nude mice].

A heterologous graft model for human breast infiltrating duct carcinoma is reported in this paper. The grafts derived from an infiltration duct carcinoma of a patient's right breast and her metastatic lymphnode mass were transplanted into the breast pads of nude mice in 1996, and the carcinoma masses were found in breast pads 31 days later. By now, the grafts of carcinoma have been transplanted into nude mice for 15 passages with a full success in 59 mice and with the biological characteristics of the original breast carcinoma. This heterologous graft model was established for the first time in China and the results suggest it be a good model for further research of breast carcinoma.

Animals↗

[Soluble IL-2 receptor levels in patients with Graves' ophthalmopathy].

OBJECTIVE: Soluble interleukin-2 receptor (sIL-2R) levels in sera with Graves' ophthmopathy was investigated for its relationship to the clinical manifestations and therapeutic effects. METHODS: sIL-2R levels were measured in sera of 41 patients with Graves' ophthalmopathy which had not yet received specific treatment for their ophthalmopathy and euthyroid during the entire study period and 49 normal subjects. RESULTS: In untreated patients, the mean levels of sIL-2R were significantly higher than those in the normal subjects (P < 0.001). There was no difference in the levels of sIL-2R between patients with hyperthyriod Graves' ophthalmopathy and those with enthyroid Graves' ophthalmopathy. The levels of sIL-2R in patients with response for corticosteoids treatment were significantly higher than that in patients with non-response for corticosteoids treatment (P < 0.001), but there were no differences between the each class present in the NOSPECS classification of ophthalmopathy. 12 patients with response for corticosreoids had lower sIL-2R levels After 3-month treatment than pertreatment. CONCLUSION: These results suggested that elevated sIL-2R levels in patients with Graves' ophthalmopathy may be derived from ophthalmopathy itself, e.g. intra-orbital activated lymphocytes, and serve as a useful parameter to evaluate clinical activity score and predict value of corticosteoids treatment outcome.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗