Development of angiogenic cell and gene therapy by transplantation of umbilical cord blood with vascular endothelial growth factor gene.

Endothelial progenitor cells (EPCs) are present in the mononuclear cells (MNCs) of umbilical cord blood and peripheral blood. To establish the efficiency of angiogenic cell and gene therapies, we transfected the human vascular endothelial growth factor (hVEGF) gene into cord blood MNCs to enhance endothelialization. MNCs from cord blood and peripheral blood were isolated and transfected with pCR3 expressing hVEGF165 or GFP by the Hemagglutinating Virus of Japan (HVJ)-envelope and the cells were cultured in endothelium basal medium-2. The number of attached cells from cord blood was higher than that from peripheral blood. Attached cells expressed Flk-1, VE-cadherin, PECAM-1, CD34, and Tie-2. The increase in the number of attached cells was transient with the transfection of vascular endothelial growth factor (VEGF) gene early in the experimental period. Flt-1 mRNA was not expressed early in the culture period, but was expressed at 2 weeks after separation. VEGF gene transfer into MNCs at 12 days after separation, i.e., when Flt-1 mRNA was expressed continuously, increased the number of attached cells. We evaluated the effects of the transplantation of cord blood MNCs expressing the hVEGF gene on regional blood flow in an ischemic area in a rat model of chronic hindlimb ischemia. Blood flow was significantly improved in nude rats that received transplanted control MNCs. Transplantation of cord blood MNCs transfected with the hVEGF gene yielded greater improvements in blood flow. These results indicate that the hVEGF gene enhances endothelialization of EPCs, and that the transplantation of cord blood MNCs transfected with the VEGF gene may be feasible for the treatment of ischemic diseases as a type of angiogenic cell and gene therapy.     

Comparison of the effects of a distal embolic protection device and an aspiration catheter during percutaneous coronary intervention in patients with acute myocardial infarction.

BACKGROUND: The beneficial effect of percutaneous coronary intervention (PCI) using stents for acute myocardial infarction (AMI) has already been demonstrated, but there is the problem that mechanical microvascular occlusion can occur because of thrombus/atheroma embolization when the PCI was performed. The aim of the present study was to retrospectively test and compare the effects of an aspiration catheter or distal embolic protection with a distal occlusion balloon catheter to prevent peripheral vascular embolization. METHODS AND RESULTS: The subjects consisted of 135 patients who underwent PCI with stenting within 12 h of the onset of chest pain caused by their first AMI. They were divided into 2 groups; the aspiration group, consisted of 81 consecutively seen patients who underwent aspiration catheter treatment between January 2001 and May 2002, and the distal protection group was the next group of 54 consecutively seen patients treated with a distal protection device between June 2002 and February 2003. The results were as follows. Thrombolysis in Myocardial Infarction (TIMI) score of 3 was obtained significantly more frequently in the distal protection group (94.4%) than in the aspiration group (79.0%). Additionally, the intensity of the cardiac muscle stain (blush score) was evaluated on coronary angiography and the rate of cases showing a blush score of 3, which indicates favorable blood perfusion at the tissue level, in the distal protection group (56.6%) was significantly greater than in the aspiration group (33.3%, p<0.01). The time to peak blood concentration of creatinine kinase was also significantly shorter in the distal protection group. CONCLUSIONS: The distal embolism protection method is superior to the aspiration method for prevention of embolization after PCI with stenting for AMI, in terms of tissue level reperfusion in myocardial recanalization therapy.     

QT dispersion correlates with systolic rather than diastolic parameters in patients receiving anthracycline treatment

OBJECTIVE: The aim of this study was to investigate the relation of QT dispersion to left ventricular (LV) systolic and diastolic function in patients undergoing anthracycline therapy. METHODS: We used echocardiography to evaluate LV systolic and diastolic function and electrocardiography to evaluate QT dispersion and corrected QT dispersion (QTcD) in patients with hematological diseases, who received anthracycline therapy. PATIENTS: Seventy-two patients with hematological diseases who were receiving anthracycline treatment were enrolled in the present study. RESULTS: LV end-diastolic diameter or LV end-systolic diameter had a significant positive correlation to QTcD (r = 0.35, p < 0.01, r = 0.43, p < 0.01). Also left ventricular ejection fraction of (LVEF) or fractional shortening had a significant negative correlation to QTcD (r = -0.46, p < 0.001, r = -0.27, p = 0.02). The highest QTcD group had a significantly larger LV end-diastolic diameter or LV end-systolic diameter than the lowest QTcD [48.5 +/- 5.7 vs. 44.4 +/- 4.5 (mm), p < 0.001, 34.1 +/- 6.4 vs. 28.8 +/- 4.3 (mm), p < 0.001] and the highest QTcD group had a significantly lower LVEF than the lowest QTcD [57.5 +/- 8.0 vs. 65.5 +/- 6.4 (%), p < 0.001]. On the other hand, none of the diastolic function markers were significantly correlated with QTcD. CONCLUSION: We concluded that increased QTcD is correlated with LV dilation and systolic dysfunction induced by anthracycline therapy, and does not reflect a dispersion of ventricular repolarization or asynchronous motion.     

Roles of phosphatidylinositol 3-kinase-Akt and NADPH oxidase in adenosine 5'-triphosphate-sensitive K+ channel function impaired by high glucose in the human artery

The present study was designed to examine roles of the phosphatidylinositol 3-kinase-Akt pathway and reduced nicotinamide-adenine dinucleotide phosphate oxidases in the reduced ATP-sensitive K(+) channel function via superoxide produced by high glucose in the human artery. We evaluated the activity of the phosphatidylinositol 3-kinase-Akt pathway, as well as reduced nicotinamide-adenine dinucleotide phosphate oxidases, the intracellular levels of superoxide and ATP-sensitive K(+) channel function in the human omental artery without endothelium. Levels of the p85-alpha subunit and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits, including p47phox, p22phox, and Rac-1, increased in the membrane fraction from arteries treated with D-glucose (20 mmol/L) accompanied by increased intracellular superoxide production. High glucose simultaneously augmented Akt phosphorylation at Ser 473, as well as Thr 308 in the human vascular smooth muscle cells. A phosphatidylinositol 3-kinase inhibitor LY294002, as well as tiron and apocynin, restored vasorelaxation and hyperpolarization in response to an ATP-sensitive K(+) channel opener levcromakalim. Therefore, it can be concluded that the activation of the phosphatidylinositol 3-kinase-Akt pathway, in combination with the translocation of p47phox, p22phox, and Rac-1, contributes to the superoxide production induced by high glucose, resulting in the impairment of ATP-sensitive K(+) channel function in the human visceral artery.     

Development of sarcoidosis during etanercept therapy

This report describes a 65-year-old woman who developed granulomatous lesions consistent with sarcoidosis during etanercept therapy for rheumatoid arthritis. Hilar and mediastinal lymphadenopathy and multiple nodules in both lung fields developed 21 months after administration of etanercept. Noncaseating epithelioid cell granulomas consistent with sarcoidosis were detected in a lung biopsy specimen and in the parietal pleura obtained via thoracotomy. Diseases showing similar histologic changes were excluded, and a diagnosis of sarcoidosis was made. Etanercept was discontinued, which resulted in symptomatic relief, improvement of oxygenation and radiologic findings. There is substantial evidence of tumor necrosis factor-alpha involvement in the induction and maintenance of granuloma formation; however, we should keep in mind that granulomatous disease, such as sarcoidosis, can develop during treatment with a tumor necrosis factor-alpha blocking agent, such as etanercept.     

Short report: isolation of Escherichia coli O157:H7 from fecal samples of cows in Vietnam

Enterohemorrhagic Escherichia coli O157:H7 was isolated for the first time in Vietnam. Shiga toxin-producing E. coli were isolated from 8 of 100 cows examined. The two strains showing serotype O157:H7 carried the eae, ehxA, and stx2c genes, but the other six were negative for the eae gene.     

Serum IgG and IgA antibodies to Chlamydia pneumoniae and severity of emphysema

OBJECTIVE: Chronic Chlamydia pneumoniae infection has been identified serologically in patients with COPD. The aim of this study was to examine whether the severity of emphysema is related to elevated antibody titres against C. pneumoniae. METHODOLOGY: We measured antibody titres against C. pneumoniae using ELISA, and assessed the severity of emphysema by the percentage of low attenuation area (%LAA) using high resolution (HR) CT in patients with COPD and in non-smoking control subjects. RESULTS: The mean %LAA was 2.2% in non-smoking controls (n = 28) and 13.3% in COPD patients (n = 94). COPD patients with a high IgG antibody index to C. pneumoniae (> or =2.0, n = 42) had a significantly higher %LAA (16.8%) than those with a low IgG index (<2.0, n = 52) (10.6%, P = 0.01). In addition, COPD patients with a high IgA antibody index (> or =2.0, n = 46) had a significantly higher %LAA (15.9%) than those with a low IgA index (<2.0, n = 48) (10.9%, P = 0.048). COPD patients with a high IgA antibody index also had a significantly lower %DLco than that associated with a low IgA index (68.1% and 80.3%, respectively, P = 0.007). There were no significant differences in age, smoking index or FEV(1)/FVC between these groups. CONCLUSION: These results suggest that high antibody titres against C. pneumoniae are linked with the severity of emphysema on high resolution CT and decreased diffusing capacity to carbon monoxide.