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Biomedical subjects

X Luo

Publications and source records attributed to X Luo.

At least 73 records · Page 4Linked to original sources
PubMed2000

Steroidogenic factor 1 (SF-1) is essential for ovarian development and function.

The orphan nuclear receptor steroidogenic factor 1 (SF-1) was identified originally as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Hints at considerably broader roles for SF-1 came from analyses of its expression pattern in mouse embryos. As anticipated, SF-1 was expressed in the adrenal glands and gonads from their early stages of development. Surprisingly, SF-1 also was expressed outside of the primary steroidogenic tissues in the anterior pituitary and hypothalamus. SF-1 knockout mice dramatically confirmed its multiple essential roles in vivo. These mice lacked adrenal glands and gonads, leading to adrenocortical insufficiency and male-to-female sex reversal of their internal and external genitalia. SF-1 knockout mice also had impaired pituitary expression of gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), confirming roles of SF-1 at all three levels of the hypothalamic-pituitary-gonadal axis. With some focus on the ovary, this review summarizes experiments that have defined essential roles of SF-1 in endocrine development, and highlights important areas for future studies.

Animals↗
PubMed2000

[Effect of irradiation on the shelf-life of aquatic products].

The effect of irradiation at doses of 0-10 kGy on the shelf-life of aquatic products was determined. The results showed that irradiation could not prolong the shelf-life of aquatic products kept at 25 degrees C. While the aquatic products were kept at refrigerator (4 degrees C), the irradiation could prolong the shelf-life and effectively reduce the total aerobic plate count. Irradiation could effectively reduce the number of coliform to less than 300/kg and eliminate Shigella shigae, Salmonella and Vibrio parahaemolyticus inoculated on shrimp, needle fish and crucian. A dose of 2.5 kGy could delay the rising of total volatile basal nitrogen in samples.

Animals↗
PubMed2000

[Establishment of monoclonal antibodies against aflatoxin M1].

The monoclonal antibodies against aflatoxin M1 were established. Spleen cells from Balb/c mice immunized with AFM1-oxime-BSA conjugate were fused with murine Sp2/0 myeloma cells. Three hybridoma cell lines secretine monoclonal antibodies against AFM1 were established after the fusion cells subcloned for 3-4 cycles. These antibodies were disignated as 3G2, 3G3 and 6G8, respectively. All of them belonged to the subtype of IgG1. The titres of the antibody in ascites ranged from 1:3.2 x 10(6)-1:20 x 10(6). There was no cross reaction between 6G8 monoclone antibody and other types of aflatoxin.

Aflatoxin M1↗
PubMed2000

Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON.

Because nitric oxide (NO) is a highly reactive signaling molecule, chemical inactivation by reaction with oxygen, superoxide, and glutathione competes with specific interactions with target proteins. NO signaling may be enhanced by adaptor proteins that couple neuronal NO synthase (nNOS) to specific target proteins. Here we identify a selective interaction of the nNOS adaptor protein CAPON with Dexras1, a brain-enriched member of the Ras family of small monomeric G proteins. We find that Dexras1 is activated by NO donors as well as by NMDA receptor-stimulated NO synthesis in cortical neurons. The importance of Dexras1 as a physiologic target of nNOS is established by the selective decrease of Dexras1 activation, but not H-Ras or four other Ras family members, in the brains of mice harboring a targeted genomic deletion of nNOS (nNOS-/-). We also find that nNOS, CAPON, and Dexras1 form a ternary complex that enhances the ability of nNOS to activate Dexras1. These findings identify Dexras1 as a novel physiologic NO effector and suggest that anchoring of nNOS to specific targets is a mechanism by which NO signaling is enhanced.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Cytotoxic aldehyde generation in heart following acute iron-loading.

Although the mechanism of myocardial failure following acute iron poisoning is not known, excess iron-catalyzed free radical generation is conjectured to play a role. The effects of time (0 to 360 minutes) on total iron concentrations, glutathione peroxidase activity, and cytotoxic aldehyde production in heart of mice (B6D2F1, n = 65) were first investigated following acute iron-loading (20 mg iron dextran i.p./mouse). In a subsequent experiment, the effects of dose (0 to 80 mg iron dextran i.p./mouse, n = 75) on the aforementioned parameters were investigated. Our results show that the concentrations of cytotoxic aldehydes: (1) significantly differ over-time, with corresponding increases in total concentrations of iron (r = 0.93, p < 0.001); and (2) increase parallel to the total dose of iron administered (r = 0.95, p < 0.001). Furthermore, dose-and time-dependent alterations to glutathione peroxidase activity are observed, which is most likely due to an acute up-regulation of the enzyme as an endogenous protective response to increased free radical activity in the heart subsequent to iron-loading. While no single mechanism is likely to account for the complex pathophysiology of acute iron-induced heart failure, our results shown that iron-loading can result in significant free radical generation, as quantified by cytotoxic aldehydes, in heart tissue of mice. This is the first report on the effects of time and dose on cytotoxic aldehyde generation and glutathione peroxidase activity in heart of mice following acute iron-loading.

Aldehydes↗
PubMed2000

Cardiolipin provides specificity for targeting of tBid to mitochondria.

Recent evidence supports the theory that mitochondrial homeostasis is the key regulatory step in apoptosis through the actions of members of the Bcl-2 family. Pro-apoptotic members of the family, such as Bax, Bad and Bid, can induce the loss of outer-membrane integrity with subsequent redistribution of pro-apoptotic proteins such as cytochrome c that are normally located in the intermembrane spaces of mitochondria. The anti-apoptotic members of the family, such as Bcl-2 and Bcl-XL, protect the integrity of the mitochondrion and prevent the release of death-inducing factors. Bid normally exists in an inactive state in the cytosol, but after cleavage by caspase 8, the carboxy-terminal portion (tBid) moves from cytosol to mitochondria, where it induces release of cytochrome c. Here we address the question of what mediates specific targeting of tBid to the mitochondria. We provide evidence that cardiolipin, which is present in mitochondrial membranes, mediates the targeting of tBid to mitochondria through a previously unknown three-helix domain in tBid. These findings implicate cardiolipin in the pathway for cytochrome c release.

Apoptosis↗
PubMed2000

Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20.

The checkpoint protein Mad2 inhibits the activity of the anaphase promoting complex by sequestering Cdc20 until all chromosomes are aligned at the metaphase plate. We report the solution structure of human Mad2 and its interaction with Cdc20. Mad2 possesses a novel three-layered alpha/beta fold with three alpha-helices packed between two beta-sheets. Using deletion mutants we identified the minimal Mad2-binding region of human Cdc20 as a 40-residue segment immediately N-terminal to the WD40 repeats. Mutagenesis and NMR titration experiments show that a C-terminal flexible region of Mad2 is required for binding to Cdc20. Mad2 and Cdc20 form a tight 1:1 heterodimeric complex in which the C-terminal segment of Mad2 becomes folded. These results provide the first structural insight into mechanisms of the spindle assembly checkpoint.

Amino Acid Sequence↗
PubMed2000

A precolumn derivatization high-performance liquid chromatographic method with improved sensitivity and specificity for the determination of astragaloside IV in Radix Astragali.

A reversed-phase high-performance liquid chromatographic method is developed for the determination of astragaloside (AGS) IV, which is known as the active constituent of Radix Astragali. The method uses precolumn derivatization with benzoyl chloride to form the benzoyl ester of AGS IV quantitatively and is carried out with a wide-ranging concentration (0.004-0.080 mg/mL) of the derivatized AGS IV. The eluent consists of 90% methanol, 4% tetrahydrofuran, 6% water, and 0.2% triethylamine, with vitamin D3 added as the internal standard.

Chromatography, High Pressure Liquid↗
PubMed2000

Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion.

Permissive hypercapnia, involving tolerance to elevated Pa(CO(2)), is associated with reduced acute lung injury (ALI), thought to result from reduced mechanical stretch, and improved outcome in ARDS. However, deliberately elevating inspired CO(2) concentration alone (therapeutic hypercapnia, TH) protects against ALI in ex vivo models. We investigated whether TH would protect against ALI in an in vivo model of lung ischemia-reperfusion (IR). Anesthetized open chest rabbits were ventilated (standard eucapnic settings), and were randomized to TH (FI(CO(2)) 0.12) versus control (FI(CO(2)) 0.00). Pa(CO(2)) and arterial pH values achieved in the TH versus CON groups were 101 +/- 3 versus 44.4 +/- 4 mm Hg and 7.10 +/- 0.03 versus 7.37 +/- 0.03, respectively. Following left lung ischemia and reperfusion, TH versus control was associated with preservation of lung mechanics, attenuation of protein leakage, reduction in pulmonary edema, and improved oxygenation. Indices of systemic protection included improved acid-base and lactate profile, in the absence of systemic hypoxemia. In the TH group, mean BALF TNF-alpha levels were 3.5% of CON levels (p < 0.01), and mean 8-isoprostane levels were 30% of CON levels (p = 0.02). Western blot analysis demonstrated reduced lung tissue nitrotyrosine in TH, indicating attenuation of tissue nitration. Finally, preliminary data suggest that TH may attenuate apoptosis following lung IR. We conclude that in the current model TH is protective versus IR lung injury and mechanisms of protection include preservation of lung mechanics, attenuation of pulmonary inflammation, and reduction of free radical mediated injury. If these findings are confirmed in additional models, TH may become a candidate for clinical testing in critical care.

Animals↗
PubMed2000

Na(+)-dependent transporters mediate HCO(3)(-) salvage across the luminal membrane of the main pancreatic duct.

To study the roles of Na(+)-dependent H(+) transporters, we characterized H(+) efflux mechanisms in the pancreatic duct in wild-type, NHE2(-/-), and NHE3(-/-) mice. The pancreatic duct expresses NHE1 in the basolateral membrane, and NHE2 and NHE3 in the luminal membrane, but does not contain NHE4 or NHE5. Basolateral Na(+)-dependent H(+) efflux in the microperfused duct was inhibited by 1.5 microM of the amiloride analogue HOE 694, consistent with expression of NHE1, whereas the luminal activity required 50 microM HOE 694 for effective inhibition, suggesting that the efflux might be mediated by NHE2. However, disruption of NHE2 had no effect on luminal transport, while disruption of the NHE3 gene reduced luminal Na(+)-dependent H(+) efflux by approximately 45%. Notably, the remaining luminal Na(+)-dependent H(+) efflux in ducts from NHE3(-/-) mice was inhibited by 50 microM HOE 694. Hence, approximately 55% of luminal H(+) efflux (or HCO(3)(-) influx) in the pancreatic duct is mediated by a novel, HOE 694-sensitive, Na(+)-dependent mechanism. H(+) transport by NHE3 and the novel transporter is inhibited by cAMP, albeit to different extents. We propose that multiple Na(+)-dependent mechanisms in the luminal membrane of the pancreatic duct absorb Na(+) and HCO(3)(-) to produce a pancreatic juice that is poor in HCO(3)(-) and rich in Cl(-) during basal secretion. Inhibition of the transporters during stimulated secretion aids in producing the HCO(3)(-)-rich pancreatic juice.

Animals↗
PubMed2000

Endothelin-1 and O2-mediated pulmonary hypertension in neonatal rats: a role for products of lipid peroxidation.

We hypothesized that reactive O2 species, or their intermediary products, generated during exposure to elevated O2 lead to pathologic endothelin-1 expression in the newborn lung. Endothelin-1 expression and 8-isoprostane content (an in vivo marker of lipid peroxidation) were examined and found to be elevated (p < 0.05) in the lungs of newborn rats with abnormal lung morphology and pulmonary hypertension, as assessed by right ventricular hypertrophy, after a 14-d exposure to 60% O2. The antioxidant and lipid hydroperoxide scavenger, U74389G (10 mg/kg), given by daily i.p. injection prevented O2-dependent right ventricular hypertrophy (p < 0.05 compared with vehicle-treated controls), but had no effect on abnormal lung morphology. Additionally, we observed that 8-isoprostane caused marked endothelin-1 mRNA up-regulation in vitro in primary rat fetal lung cell cultures. We conclude that reactive O2 species, or their bioactive intermediaries, are causative in O2-mediated pulmonary hypertension and endothelin-1 up-regulation. It is likely that the bioactive lipid peroxidation product, 8-isoprostane, plays a key role in pathologic endothelin-1 expression and pulmonary hypertension during oxidant stress.

Animals↗
PubMed2000

Changes in expression of platelet-derived growth factor and its receptors in the lungs of newborn rats exposed to air or 60% O(2).

PDGF-related gene expression has been well characterized during fetal rat lung development and adult rat lung injury, but not during normal postnatal lung growth or injury. Lung expression of the mRNA for PDGF-A, -B, -alpha R, and -beta R and immunoreactive PDGF-AA, -BB, -alpha R, and -beta R were assessed in rat pups raised in air or 60% O(2) for up to 14 d after birth. Expression of mRNA and immunoreactive ligand did not correlate for pups raised in air. Immunoreactive PDGF-alpha R and -beta R, but not PDGF-AA and -BB, were evident throughout the lung at birth. Both PDGF-AA and -BB were evident in airway epithelium, PDGF-BB in alveolar epithelial cells and PDGF-AA was widely distributed in parenchymal tissue at 4 d. PDGF-alpha R was localized to airway epithelium, and PDGF-beta R to subendothelial perivascular regions and to airway and alveolar epithelium at 4 d. Immunoreactive PDGF ligands all declined after 4 d. Intraperitoneal injection of neutralizing antibodies or truncated soluble receptors to PDGF-BB reduced lung DNA synthesis in air. Exposure to 60% O(2) significantly increased mRNA for PDGF-B, -beta R, and -alpha R, but not PDGF-A, relative to air-exposed lung at various time points after birth. PDGF-A, -B, and -alpha R immunoreactivities in these lungs were reduced and delayed, consistent with a global inhibition of lung growth. Pups exposed to 60% O(2) had a similar distribution of PDGF-beta R to that seen in air, except that at 14 d PDGF-beta R was distributed throughout the lung parenchyma. We conclude that PDGF ligands and receptors are important for normal postnatal lung growth and that their expression is delayed by O(2) exposure.

Animals↗
PubMed2000

Tumor amplified protein expression therapy: Salmonella as a tumor-selective protein delivery vector.

Attenuated strains of Salmonella typhimurium, VNP20009 and YS7212, when injected systemically to tumor-bearing mice, accumulated preferentially in tumors at levels at least 200-fold and, more commonly, 1000-fold greater than in other normal tissues. This selectivity occurred in subcutaneously implanted murine tumors, including B16F10 melanoma, M27 lung carcinoma, and colon 38 carcinoma. The preferential accumulation was also manifested in animals bearing human tumor xenografts, including Lox, C8186, DLD1, SW620, HCT116, HTB177, DU145, MDA-MB-231, and Caki. Four to five days after a single IV injection of 1 x 10(6) colony-forming unit (cfu)/mouse, we routinely detected VNP20009 proliferation and accumulation at levels ranging from 1 x 10(8) to 2 x 10(9) cfu/g tumor. The amount of VNP20009 accumulated in the liver ranged from 3 x 10(4) to 2 x 10(6) cfu/g. The distribution of Salmonella in tumors was homogenous; YS7212 could be detected from the periphery to the interior portion of the tumors. Using mice with various immunodeficiencies, we also discovered the same preferential accumulation of Salmonella in tumors implanted in these mice. The use of Salmonella as a protein delivery vector was shown by IV administration of the bacteria expressing either green fluorescent protein (GFP) or cytosine deaminase (CD) into tumor-bearing mice. GFP and CD were detected in tumors, but not in livers, taken from mice inoculated with Salmonella carrying these genes. Bacteria accumulation and CD expression persisted in the tumors for up to 14 days after a single bolus IV administration of bacteria to tumor-bearing mice.

Animals↗
PubMed2000

[Study of covalently immobilizing heparin to polyetherurethane surface].

In this paper an approach of covalently immobilizing heparin to the surface of polyetherurethane without functional groups was studied. By quantitation of amino groups on PEU surface, the appropriate hydrolysis condition to PEU was determined. The assays of the heparin content heparinized PEU and the time of recalcification proved the above approach comparatively ideal.

Heparin↗
PubMed2000

Expression of metallothionein in invasive ductal breast cancer in relation to prognosis.

The aim of this study was to assess the presence and clinical significance of metallothionein (MT) in primary invasive ductal carcinoma of the breast. We investigated 96 cases of routinely fixed and paraffin-embedded primary breast carcinomas with the immunohistochemical method. Positive staining for MT was observed in 52.1% of specimen. In most cases both nuclear and cytoplasmic staining was seen. A statistically significant association was found between MT-positive staining and nuclear grade (p < 0.01). MT-positive cases had a significantly poorer prognosis when compared with the MT-negative cases (p < 0.01). We concluded that the MT expression may be of a prognostic value for primary invasive ductal carcinoma of the breast and is possibly an indicator of more aggressive and less differentiated carcinoma cells.

Adult↗