Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA

Influence of terahertz waves on the fiber direction of CFRP composite laminates

The importance of Carbon-fiber reinforced plastics (CFRP) are widely utilized due to more high performance in engineering structures. It was well known that a nondestructive technique would be very beneficial. A new terahertz radiation has been recognized for their importance in technological applications. Recently, T-ray (terahertz ray) advances of technology and instrumentation has provided a probing field on the electromagnetic spectrum. The THz-TDS can be considered as a useful tool using general non-conducting materials; however it is quite limited to conducting materials. In order to solve various material properties, the index of refraction (n) and the absorption coefficient (α) are derived in reflective and transmission configuration using the terahertz time domain spectroscopy. However, the T-ray is limited in order to penetrate a conducting material to some degree. Here, the T-ray would not go through easily the CFRP composite laminates since carbon fibers are electrically conducting while the epoxy matrix is not. So, investigation of terahertz time domain spectroscopy (THz TDS) was made and reflection and transmission configurations were studied for a 48-ply thermoplastic PPS (poly-phenylene sulfide)-based CFRP solid laminate. It is found that the electrical conductivity of CFRP composites depends on the direction of unidirectional fibers. Also, the T-ray could penetrate a CFRP composite laminate a few ply based on the E-filed (Electrical field) of carbon fibers. The terahertz scanning images were made at the angles ranged from 0° to 180° with respect to the nominal fiber axis. So, the images were mapped out based on the electrical field (E-field) direction in the CFRP solid laminates. Also, using two-dimensional spatial Fourier transform, interface C-scan images were transformed into quantitatively angular distribution plots to show the fiber orientation information therein and to predict the orientation of the ply

Constraints on the Phase Plane of the Dark Energy Equation of State

Classification of dark energy models in the plane of w and w', where w is the dark energy equation of state and w' its time-derivative in units of the Hubble time, has been studied in the literature. We take the current SN Ia, CMB and BAO data, invoke a widely used parametrization of the dark energy equation of state, and obtain the constraints on the w -w' plane. We find that dark energy models including the cosmological constant, phantom, non-phantom barotropic fluids, and monotonic up-rolling quintessence are ruled out at the 68.3% confidence level based on the current observational data. Down-rolling quintessence, including the thawing and the freezing models, is consistent with the current observations. All the above-mentioned models are still consistent with the data at the 95.4% confidence level.Comment: 14 pages, 5 figures, "Test of the method" added in Sec. 4 in v

Superior canal dehiscence in a patient with three failed stapedectomy operations for otosclerosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case illustrates that superior semicircular canal dehiscence syndrome can be associated with a "pseudo"-conductive hearing loss, a symptom that overlaps with the clinical appearance of otosclerosis.</p> <p>Case presentation</p> <p>We present the case of a 48-year-old German Caucasian woman presenting with hearing loss on the left side and vertigo. She had undergone three previous stapedectomies for hearing improvement. Reformatted high-resolution computed tomographic scanning and the patient's history confirmed the diagnosis of concurrent canal dehiscence syndrome.</p> <p>Conclusion</p> <p>Failure of hearing improvement after otosclerosis surgery may indicate an alternative underlying diagnosis which should be explored by further appropriate evaluation.</p

Effect of prolonged HAART on oral colonization with Candida and candidiasis

BACKGROUND: Progressive cell-mediated immunodeficiency with decrease of CD4+ lymphocyte count to less than or equal to 200 cells/mm(3 )is a major risk factor for colonization with Candida species and development of candidiasis. Oropharyngeal candidiasis may occur in up to 90% of human immunodeficiency virus (HIV)-infected patients during the course of the disease. This study is to determine the effect of prolonged highly active antiretroviral therapy (HAART) on oropharyngeal colonization with Candida species and oral candidiasis. METHODS: A prospective, longitudinal follow-up study in HIV-infected patients receiving HAART. RESULTS: The mean CD4+ count increased from 232.5 to 316 cells/mm(3 )and the proportion of patients whose CD4+ count less than 200 cells/mm(3 )decreased from 50.0% to 28.9% (p = 0.0003) in patients receiving HAART for at least 2 years. The prevalence of oral candidiasis decreased from 10.6% to 2.1% (p = 0.004). The decrease in Candida colonization was less impressive, falling from 57.8% to 46.5 % (p = 0.06). Of the 142 patients enrolled in at least two surveys, 48 (33.8%) remained colonized with Candida and 42 (29.6%) remained negative. In the remaining 52 patients, 34 switched from culture positive to negative, and an increase in CD4+ lymphocytes was noted in 91.2% of them. Among the 18 patients who switched from culture negative to positive, 61.1% also demonstrated an increase in CD4+ lymphocyte count (p = 0.01). CONCLUSION: These findings indicate that HAART is highly effective in decreasing oral candidiasis in association with a rise in CD4+ lymphocyte counts, but only marginally effective in eliminating Candida from the oropharynx

Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans