A Ubiquitous Chromatin Opening Element (UCOE) Confers Resistance to DNA Methylation�Cmediated Silencing of Lentiviral Vectors

DNA methylation may restrict the activity of gene transfer vectors due to inadvertent silencing. In P19 embryonic carcinoma cells in vitro, we found that transgene expression regulated by the SFFV LTR and EF1α promoter declined rapidly within 16 days, but for A2UCOE derived from the human HNRPA2B1-CBX3 housekeeping gene locus, remained completely stable. Silencing correlated with extensive epigenetic methylation of CpG sites, whereas the A2UCOE was almost completely resistant. Linking of the A2UCOE upstream of the SFFV LTR protected this element from both DNA methylation and silencing. Analysis of engrafted hematopoietic cells in vivo transduced with the same vectors revealed a similar pattern. The A2UCOE displayed little or no methylation in either primary or secondary graft recipients, and gene expression profiles were highly conserved between the two groups. These studies provide convincing evidence that DNA methylation plays a direct role in regulating self-inactivating (SIN) lentiviral transgene expression, and that the stability of expression from the A2UCOE is, at least in part, due to methylation resistance. The A2UCOE therefore has considerable utility for gene therapy applications where reliable and sustained gene expression is desirable.     

Plasma metabolites after 2-deoxy-D-glucose in rats with brain dopamine-depleting lesions

Rats with selective brain dopamine-depleting lesions produced by 6-hydroxydopamine failed to increase their food intake after 2-deoxy-D-glucose administration. Their hyperglycemic response to 2DG was identical to that of intact controls. Neither group showed significant mobilization of free fatty acids or production of ketones.     

瘦素有望成为诊治肿瘤的一个关键点

对瘦素与肿瘤的最新研究进展进行综述,并阐明瘦素参与调节肿瘤发生、发展的可能机制,它可能有望成为早期诊治肿瘤的一个关键点。     

Laparoscopic bilateral nephrectomy for renin-mediated hypertension

Hypertension arising from retained native kidneys complicates the management of recipients of renal transplants. Reluctance to administer angiontensin-converting enzyme inhibitor (ACEI) drugs to patients taking cyclosporine has reopened the question of performing native nephrectomies for poorly controlled, renin-dependent hypertension. We report the first published cases of simultaneous bilateral laparoscopic nephrectomies in 2 patients: 1 in preparation for living-related donor transplantation and the other ten months following cadaver transplantation in a patient whose end-stage renal disease was from malignant nephrosclerosis. Both had very severe hypertension resistant to multiple drugs and both became normotensive with little or no antihypertensive medication following nephrectomies. A bilateral nephrectomy is currently feasible using a laparoscopic approach.     

MR vascular imaging with a fast gradient refocusing pulse sequence and reformatted images from transaxial sections

The authors present a method for obtaining magnetic resonance (MR) images of intra- and extracranial vessels from thin contiguous transaxial sections. A section-selective gradient refocusing pulse sequence with a short repetition time caused flow-related enhancement from spins that flowed perpendicular to the transaxial sections. The signal was further enhanced by means of flow compensation gradients to rephase any phase shifts resulting from moving spins in the presence of the imaging gradients. Coronal and sagittal sections, reformatted from multiple transaxial sections, are shown to have excellent vessel contrast without the use of contrast material. These images were obtained in 12 minutes of acquisition time from as many as 60 sections of 3-mm thickness. Such a technique shows significant promise for MR angiography.     

Substance abuse during pregnancy in a rural population.

Drug abuse during pregnancy in rural populations has received less attention than that in urban populations. Urban studies have reported alarming rates, but it is unknown whether the situation is the same in rural areas. To investigate this, urine samples were collected anonymously from 181 pregnant women who presented to the University of Missouri clinics for care and who resided in communities of less than 25,000. Each urine specimen was tested for cocaine, marijuana, amphetamines, barbiturates, opiates, phencyclidine, benzodiazepines, ethanol, and nicotine. Of the 181 specimens, 83 (46%) contained nicotine, 17 (9.4%) contained marijuana, and one each (0.6%) tested positive for cocaine, barbiturates, ethanol, and benzodiazepines. No other tested substances were detected. Excluding nicotine and ethanol, 20 (11%) of the urine samples tested positive for the screened substances. Review of the prenatal records revealed that 46% of the women reported using tobacco, 15% reported using alcohol, and 8.3% reported illicit drug use during pregnancy. This study indicates that there is a substantial drug abuse problem in rural populations, and that the profile of abuse differs from that of urban populations. Tobacco, ethanol, and marijuana were the most prevalent substances abused during pregnancy, but cocaine was a minor problem. This information may help in directing resources to reduce drug abuse during pregnancy.