Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and (19)F-NMR.

Specific arrestin conformations are coupled to distinct downstream effectors, which underlie the functions of many G-protein-coupled receptors (GPCRs). Here, using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance ((19)F-NMR) spectroscopy, we demonstrate that distinct receptor phospho-barcodes are translated to specific ß-arrestin-1 conformations and direct selective signalling. With its phosphate-binding concave surface, ß-arrestin-1 'reads' the message in the receptor phospho-C-tails and distinct phospho-interaction patterns are revealed by (19)F-NMR. Whereas all functional phosphopeptides interact with a common phosphate binding site and induce the movements of finger and middle loops, different phospho-interaction patterns induce distinct structural states of ß-arrestin-1 that are coupled to distinct arrestin functions. Only clathrin recognizes and stabilizes GRK2-specific ß-arrestin-1 conformations. The identified receptor-phospho-selective mechanism for arrestin conformation and the spacing of the multiple phosphate-binding sites in the arrestin enable arrestin to recognize plethora phosphorylation states of numerous GPCRs, contributing to the functional diversity of receptors.

Structural and spectropscopic studies of a three-dimensional hydrogen-bonded copper(II) complex: aqua[bis(pyridin-2-ylcarbonyl)amidato]cyanidocopper(II).

The preparation and X-ray and spectroscopic studies of the title copper(II) complex, [Cu(C12H8N3O2)(CN)(H2O)], are reported. The Cu(II) cation is five-coordinated, forming a distorted square-planar pyramid with an Addison τ parameter of 0.14. The UV-vis spectrum shows a d-d transition of the Cu(II) centre at 638 nm, and the electron paramagnetic resonance (EPR) spectrum confirms that the Cu(II) cation has an axial symmetry coordination and that the unpaired electrons occupy the d(x(2)-y(2)) orbital. Cyclic voltammetric studies show two irreversible oxidation and reduction peaks.

Cadmium is a potent inhibitor of PPM phosphatases and targets the M1 binding site.

The heavy metal cadmium is a non-degradable pollutant. By screening the effects of a panel of metal ions on the phosphatase activity, we unexpectedly identified cadmium as a potent inhibitor of PPM1A and PPM1G. In contrast, low micromolar concentrations of cadmium did not inhibit PP1 or tyrosine phosphatases. Kinetic studies revealed that cadmium inhibits PPM phosphatases through the M1 metal ion binding site. In particular, the negative charged D441 in PPM1G specific recognized cadmium. Our results suggest that cadmium is likely a potent inhibitor of most PPM family members except for PHLPPs. Furthermore, we demonstrated that cadmium inhibits PPM1A-regulated MAPK signaling and PPM1G-regulated AKT signaling potently in vivo. Cadmium reversed PPM1A-induced cell cycle arrest and cadmium insensitive PPM1A mutant rescued cadmium induced cell death. Taken together, these findings provide a better understanding of the effects of the toxicity of cadmium in the contexts of human physiology and pathology.

[Percutaneous intradiscal oxygen-ozone injection for lumbar disc herniation: no need of perioperative antibiotic prophylaxis].

OBJECTIVE: To evaluate the feasibility of no antibiotic administration to prevent infection during the perioperative period of percutaneous intradiscal ozone-injection for treatment of lumbar disc herniation. METHODS: Seventy-two patients with lumbar disc herniation but normal body temperature as well as normal results of three routine tests (blood, urine, stool) and C-reactive protein (CRP) level were randomly divided into two groups. The patients in prophylaxis group were given cephalothin V(2.0 g) intravenous 30 min before the operation, and the control group did not use any antibiotics. All the patients were injected with 6-10 ml ozone (40 microg/ml) for medical use into the discs with 21G needles under fluoroscopic guidance, followed by 10 ml ozone into the paravertebral space. Three days later the general examinations and CRP measurement were repeated. RESULTS: No infection was found in these patients, nor were any significant differences noted in the results of the examinations between the two groups after controlling in patients with above-normal white blood cell count, neutrophil percentage and CRP level. CONCLUSION: Prophylaxis antibiotics is not necessary during the perioperative period of percutaneous intradiscal ozone injection for lumbar disc herniation.

[Necessity of prophylactic antibiotics in patients with primary liver cancer undergoing transcatheter arterial chemoembolization: a prospective study].

OBJECTIVE: To investigate the necessity of prophylactic administration of antibiotic in patients with primary liver cancer undergoing transcatheter arterial chemoembolization (TACE). METHODS: Sixty patients without preoperative infection were randomized into two groups to receive a single dose of cefazolin (PA group) prior to TACE or no prophylactic antibiotics (NONE group). The incidence of postoperative infection was compared. RESULTS: The incidence of postoperative infection was 3.4% (1/29) in NONE group and 3.2% (1/31) in PA group, without significant difference between the two groups (P>0.05). CONCLUSION: Prophylactic antibiotics are not necessary for patients with primary liver cancer prior to TACE.

[Clinical application of 16-slice spiral CT coronary angiography].

OBJECTIVE: To assess the clinical value of multislice spiral CT coronary angiography (MSCTCA). METHODS: Totally 79 patients were examined with MSCTCA and the CT images were reconstructed by several methods to analyze the factors crucial for the image quality, the ability of MSCT displaying the coronary artery vessels, along with the nature and calcification degrees of the plaques. The presence as well as the degree of vascular stenosis, visualization of the bypass graft, implanted stents and patency of the vessels were evaluated. RESULTS: The left main coronary artery and the left anterior descending artery were all best visualized in 75% R-R phases while the right coronary artery and the left circumflex artery in 62.5% R-R phases. CT images obtained by volume rendering showed the best quality at 75% R-R phases. 16-slice spiral CT was able to display from the primary to the tertiary, and even the quaternary branches of the coronary artery, and clearly displayed the coronary plaques, stenosis, implanted stents and bypass grafts. CONCLUSION: MSCTCA has a good clinical value in the primary identification of coronary heart disease and reexamination after revascularization.

[18F-Fluorodeoxyglucose uptake in hepatocellular carcinoma on positron emission tomography correlates with alpha-fetoprotein].

OBJECTIVE: To investigate whether (18)F-fluorodexyglucose (FDG) uptake in the primary hepatocellular carcinoma (HCC) correlates with serum alpha-fetoprotein (AFP). METHODS: Forty-five patients with histologically confirmed HCC underwent whole-body (18)F-FDG PET examination. Standardized uptake value (SUV) and tumor-to-nontumor ratio of the SUV (SUVratio) were calculated, and the relationship between serum AFP and glucose metabolism in HCC was analyzed. RESULTS: Of the 45 cases, the primary tumor and metastatic lymph nodes were clearly displayed on PET images in 43 cases and the well-differentiated tumors were shown negative in the other 2 cases. A linear correlation of the AFP with SUV (r=0.426, P<0.05) and SUVratio (r=0.532, P<0.001) was noted. CONCLUSION: Serum AFP correlates significantly with both SUV and SUN ratio, indicating that AFP is involved in glucose metabolism and cell proliferation in HCC.

Value of angiography in the diagnosis of patients with small kidney.

OBJECTIVE: To explore the diagnostic value of angiography in small kidney patients. METHODS: Angiographies were performed in 32 patients with small kidney of unknown etiology or with suspected renal arterial stenosis (RAS). RESULTS: Twelve cases of renal atrophy due to RAS were diagnosed by angiography, which demonstrated renal artery stenoses or occlusions. Angiography of 17 patients with nephrogenic renal atrophy displayed homogeneous shrinkage of the renal arteries except in the ostium. In 3 patients with renal hypoplasia, angiography showed narrowed renal arteries and tiny renal arterial branches. CONCLUSION: Renal artery angiography is of important values in the differential diagnosis between renal atrophy due to RAS, nephrogenic renal atrophy and non-renovascular renal atrophy, and renal hypoplasia.

[Comparison of digital radiography and conventional X-ray in the diagnosis of solitary pulmonary nodule with receiver operating characteristic analysis].

OBJECTIVE: To compare digital radiographs with conventional radiographs in the detection of solitary pulmonary nodules. METHODS: Thirty patients with solitary pulmonary nodule and 30 cases without pulmonary nodules were enrolled in the study. The existence of solitary pulmonary nodule was confirmed by chest computed tomography (CT) as well as biopsy. All patients examined by both digital radiography (group A) and conventional radiographs (group B) were reviewed by four experienced chest radiologists and four residents. Assessment was performed with receiver operating characteristic (ROC) analysis of the images in both groups. RESULTS: (1) Observer performance of the experienced radiologists in group B (Az=0.838) was superior to that in group A (Az=0.816) (P<0.05) in detection of solitary pulmonary nodule. For the residents, observer performance in group B (Az=0.842) was superior to that in group A (Az=0.712) (P<0.05). (2) There was no difference between the two groups (P=0.272), for the judgement of benign or malignant solitary pulmonary nodule. CONCLUSIONS: Digital radiographs is superior to conventional radiographs in detection of solitary pulmonary nodule. However, there was no significant differences in discrimination between benign and malignant solitary pulmonary nodules in the two groups.