Biomedical subjects

Jun Xia

Publications and source records attributed to Jun Xia.

25 records · Page 2Linked to original sources

PubMed2004

Structural determinants of constitutive androstane receptor required for its glucocorticoid receptor interacting protein-1-mediated nuclear accumulation.

Nuclear translocation of constitutive androstane receptor (CAR) is a primary mechanism for the induction of cytochrome P450 genes by phenobarbital (PB). We have shown that exogenous expression of the p160 coactivator glucocorticoid receptor interacting protein-1 (GRIP1) in hepatocytes in vivo can mediate PB-independent nuclear accumulation of murine CAR (mCAR). To understand the mechanism of this PB-independent nuclear accumulation, we have examined the mCAR structural determinants of its GRIP1-mediated nuclear localization. Mutations of the xenobiotic response sequence (XRS), which had been shown to block PB-dependent nuclear translocation of human CAR in mouse hepatocytes in vivo, also blocked GRIP1-mediated nuclear accumulation of mCAR in mouse hepatocytes in vivo and further blocked nuclear localization in cultured HepG2 cells. A leucine 326 XRS mutant retained partial transcriptional activity, but mutations of three leucines in the XRS eliminated transcriptional activity in HepG2 cells, suggesting that the translocation function of the XRS overlaps with transcriptional functions. Mutation of the activation function 2 motif, by deletion of the C-terminal 8 amino acids, also reduced nuclear localization by both PB treatment and GRIP1 expression in hepatocytes in vivo, suggesting that either interaction with GRIP1 through this motif or active CAR was required for the nuclear localization. The localization of a DNA-binding domain mutant was essentially unchanged by coexpression of GRIP1, although without GRIP1 coexpression, this mutant expressed exhibited a more nuclear localization compared with wild type. The results are most consistent with a model in which GRIP1 interaction and activation of mCAR in the nucleus result in retention and accumulation of mCAR in the nucleus in untreated animals. The model requires that mCAR is constantly shuttling between the nucleus and cytoplasm even in untreated animals in which mCAR is predominantly cytoplasmic.

Active Transport, Cell Nucleus↗

PubMed2004

Volumetric MRI analysis of the amygdala and hippocampus in subjects with major depression.

In order to explore the MRI volume of the amygdala and hippocampus in patients with major depression, quantitative MRI of the amygdala and hippocampus were studied in 22 patients with major depression and compared with 13 age-matched controls. The results showed that both groups exhibited similar significant hippocampal asymmetry (left smaller than right). The volume of the bilateral hippocampus was significantly smaller in the major depression group than that in control group. The patients had significant asymmetry of the amygdalar volumes (right smaller than left). No correlation was found between hippocampal volume abnormalities and ill duration. It was concluded that the hippocampus and amygdala within limbic-cortical networks may play a crucial role in the pathogenesis of major depression.

Adult↗

PubMed2003

Cell therapy with a tissue-engineered kidney reduces the multiple-organ consequences of septic shock.

OBJECTIVE: Gram-negative septic shock has a clinical mortality rate approaching 50%. The cause of death is secondary to a systemic inflammatory response syndrome with resulting cardiovascular collapse, ischemic damage to vital organs, and multiple-organ systems failure. Renal tubule cell injury occurs early in septic shock but is not clinically appreciated. Since renal tubule cells appear to play a critical role in the immunoregulation of stress states, renal cell therapy during septic shock may alter the detrimental multiple-organ consequences of systemic Gram-negative infection. The development of a tissue-engineered bioartificial kidney consisting of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 109 renal proximal tubule cells may be a new therapeutic approach to this clinical disorder. DESIGN: Laboratory study. SETTING: University medical school. SUBJECTS: Pigs weighing 30-35 kg. INTERVENTIONS: To assess the effect of the bioartificial kidney and the RAD in septic shock, pigs were administered 30 x 10(10) bacteria/kg body weight of Escherichia coli into the peritoneal cavity and within 1 hr were immediately placed in a continuous venovenous hemofiltration extracorporeal circuit with either a sham RAD without cells or a RAD with cells. MEASUREMENTS AND MAIN RESULTS: In this animal model, septic shock resulted within hours in acute tubule necrosis in the kidneys of all animals. Renal cell therapy resulted in significantly higher cardiac outputs and renal blood flow rates in treated animals compared with sham controls. RAD treatment also was associated with significantly lower plasma circulating concentrations of interleukin-6 and interferon-gamma compared with sham-treated animals. IL-6 release rates from peripheral blood mononuclear cells isolated from RAD-treated animals were significantly higher after endotoxin stimulation than those isolated from control animals. These physiologic and molecular alterations were associated with nearly a doubling of the average survival time in the RAD-treated group compared with the sham control group. CONCLUSION: These results demonstrate that renal cell therapy ameliorates cardiac and vascular dysfunction, alters systemic cytokine abnormalities, and improves survival time in a large animal model of Gram-negative septic shock. A cell therapeutic approach with a tissue-engineered bioartificial kidney may be a new treatment modality for this current unmet medical need.

Acute Kidney Injury↗

PubMed2003

Endothelial cell signaling during conducted vasomotor responses.

ACh and KCl stimulate vasomotor responses that spread rapidly and bidirectionally along arteriole walls, most likely via spread of electric current or Ca2+ through gap junctions. We examined these possibilities with isolated, cannulated, and perfused hamster cheek pouch arterioles (50- to 80-microm resting diameter). After intraluminal loading of 2 microM fluo 3 to measure Ca2+ or 1 microM di-8-ANEPPS to measure membrane potential, photometric techniques were used to selectively measure changes in intracellular Ca2+ concentration ([Ca2+]i) or membrane potential in endothelial cells. Activation of the endothelium by micropipette application of ACh (10-4 M, 1.0-s pulse) to a short segment of arteriole (100-200 microm) increased endothelial cell [Ca2+]i and caused hyperpolarization at the site of stimulation. This response was followed rapidly by vasodilation of the entire arteriole ( approximately 2-mm length). Change in membrane potential always preceded dilation, both at the site of stimulation and at distant sites along the arteriole. In contrast, an increase in endothelial cell [Ca2+]i was observed only at the application site. Micropipette application of KCl, which can depolarize both smooth muscle and endothelial cells (250 mM, 2.5-s pulse), also caused a rapid, spreading response consisting of depolarization followed by vasoconstriction. With KCl stimulation, in addition to changes in membrane potential, increases in endothelial cell [Ca2+]i were observed at distant sites not directly exposed to KCl. The rapid longitudinal spread of both hyperpolarizing and depolarizing responses support electrical coupling as the mode of signal transmission along the arteriolar length. In addition, the relatively short distance between heterologous cell types enables the superimposed radial Ca2+ signaling between smooth muscle and endothelial cells to modulate vasomotor responses.

Acetylcholine↗

PubMed2002

[Expression of c-terminal of Parkin in E. coli and the preparation of antiserum].

OBJECTIVE: To clone and express 3'-terminal of Parkin gene in E. coli, and prepare its antiserum for further study. METHODS: The glutathion-sulfate-transferase (GST) fusion expression plasmid of 3'-terminal of Parkin gene (937-1959 bp) was constructed and transferred to JM 105. After being treated with Triton-100 (1%) and Tween-20 (1%) and purified with affinity chromatograph, GST-Parkin C was used to immunize New Zealand rabbits to acquire antiserum. Antiserum was analysed with immunoblot. RESULTS: The GST-Parkin C protein was expressed in JM 105, existing in the form of inclusion body with a molecular weight of around 42 kD; The purity of GST-Parkin C was up to 95%; the titer of antiserum was 1:64; Immunoblotting showed that the prepared antiserum could react specifically with 51.6 kD protein extracted from the mouse brain. CONCLUSION: A high level of expression of GST-Parkin C is obtained in JM 105, and its antiserum can be prepared successfully.

Animals↗

PubMed2002

Investigation of the elemental distribution in iliac crests of female New Zealand rabbits using NAA.

This article deals with an osteoporosis model using New Zealand rabbits in order to study the function of inorganic elements for women patients with osteoporosis. Thirty cases of iliac crests were collected and determined using the neutron activation analysis technique. The results show that the fluorine concentrations in the experimental group are higher than those in the control group and that the magnesium concentrations are significantly lower (p < 0.001), but the concentrations of potassium, sodium, calcium, barium, manganese, and strontium show no significant differences. Combined with the serum biochemical markers of bone formation and resorption, the physiological functions of some metal elements in bone are also discussed.

Acid Phosphatase↗

PubMedDate not supplied

Surgical treatment for giant solid tumors of the mediastinum: a study of 26 cases.

Twenty-six patients with giant solid tumors of the mediastinum (GSTM) were treated surgically from 1975 to 2000. Femorofemoral cardiopulmonary bypass (CPB) was used before induction of anesthesia as a precaution against total tracheal occlusion in two cases. Resection of the tumor was accomplished in all patients, combined with partial pericardium resection in five cases, left upper lobe of lung resection in two cases, and reconstruction of the superior vena cava (SVC) and innominate vein in four cases. The weights of resected tumors ranged from 1.1 to 4.8 kg, with an average of 2.2 kg. The majority were benign (22 of 26, 84.6%). The postoperative complications included two cases with recurrent laryngeal nerve injury, three cases with wound infection, and two cases with dilatant pneumonedema. Diagnosis of GSTM was not difficult based on imaging and needle biopsy. Femorofemoral CPB is recommended before induction of anesthesia for patients with superior airway obstruction and superior vena cava occlusion. Perioperative management includes strict hemostasis, proper chest wall reconstruction, and prevention of re-expansion pulmonary edema.

Adolescent↗