Identification and characterization of multiple osmotic response sequences in the human aldose reductase gene

Aldose reductase (AR) has been implicated in osmoregulation in the kidney because it reduces glucose to sorbitol, which can serve as an osmolite. Under hyperosmotic stress, transcription of this gene is induced to increase the enzyme level. This mode of osmotic regulation of AR gene expression has been observed in a number of nonrenal cells as well, suggesting that this is a common response to hyperosmotic stress. We have identified a 132-base pair sequence 1 kilobase pairs upstream of the transcription start site of the human AR gene that enhances the transcription activity of the AR promoter as well as that of the SV40 promoter when the cells are under hyperosmotic stress. Within this 132-base pair sequence, there are three sequences that resemble TonE, the tonicity response element of the canine betaine transporter gene, and the osmotic response element of the rabbit AR gene, suggesting that the mechanism of osmotic regulation of gene expression in these animals is similar. These three sequences are designated as OreA, OreB, and OreC respectively, Analysis of the mouse AR gene also revealed that these three sequences are highly conserved between the mouse and human. Results from site-directed mutagenesis and gel mobility shift assays suggested that the OreC is the most important element for the osmotic response and cooperative interaction among the three elements in the human AR gene is essential for their enhancer function. The human aldose reductase gene osmotic response elements are the first osmotic response elements characterized in human.published_or_final_versio

Fast detection of venous air embolism in Doppler heart sound using the wavelet transform

The introduction of air bubbles into the systemic circulation can result in significant morbidity. Real-time monitoring of continuous heart sound in patients detected by precordial Doppler ultrasound is, thus, vital for early detection of venous air embolism (VAE) during surgery. In this study, the multiscale feature of wavelet transforms (WT's) is exploited to examine the embolic Doppler heart sound (DHS) during intravenous air injections in dogs. As both humans and dogs share similar physiological conditions, the authors' methods and results for dogs are expected to be applicable to humans. The WT of DHS at scale 2 j(j=1,2) selectively magnified the power of embolic, but not the normal, heart sound. Statistically, the enhanced embolic power was found to be sensitive (P<0.01 at 0.01 ml of injected air) and correlated significantly (P<0.0005, τ=0.83) with the volume of injected air from 0.01 to 0.10 ml. A fast detection algorithm of O(N) complexity with unit complexity constant for VAE was developed (processing speed=8 ms per heartbeat), which confirmed the feasibility of real-time processing for both humans and dogs.published_or_final_versio

Volume Estimation by Wavelet Transform of Doppler Heart Sound During Venous Air-Embolism in Dogs

The Doppler heart sound signals detected by the precordial Doppler ultrasound method under simulated sub clinical and clinically significant venous air embolism were studied in anesthetized dogs. Signal processing using wavelet transform enhanced the contrast of embolic to normal signal, facilitating automatic detection and extraction of embolic signal simply by thresholding. Linear relationship of good correlation coefficient was obtained in log-log scale between the subclinical volume of injected air and the corresponding embolic signal power in all dogs. The calibration curve was found to be good estimate of the volume of embolic air during simulated clinically significant venous air embolism. Hence, we overcame the need of constant human attention for detecting venous air embolism and the lack of quantitative information on the volume of embolic air in the traditional precordial Doppler ultrasound method by the present approach.published_or_final_versio

Semi-automatic tumor boundary detection in MR image sequences

The authors present a semi-automatic approach for the detection of tumor boundary in MR image sequences. An initial slice with an obvious tumor is selected from the image sequence. The tumor is roughly segmented using fuzzy c-means algorithm and its boundary can be further refined by region and contour deformation. For the rest of the slices, the initial plan applied for each slice is extracted from the resulting boundary of the previous slice. The tumor boundary is located using region and contour deformation. Performance of our approach is evaluated on the MR image sequence. Comparisons with manual tracing show the accuracy and effectiveness of our approach.published_or_final_versio

Tumor boundary extraction in multislice MR brain images using region and contour deformation

In this paper, we present a new approach for the extraction of brain tumor boundary in a series of 2D MR image slices. The shape and position of tumor in one slice could be assumed to be similar to that in its neighboring slices. Using this correlation between consecutive images, the initial plan applied for each slice is extracted from the resulting boundary of the previous slice. The tumor boundary is located using region and contour deformation, which tolerates a rough initial plan. Therefore, only one coarse manual initial plan is required for the whole series of MR image slices. Performance of our approach is evaluated on MR image set. Comparisons with manual tracing show the accuracy and effectiveness of our approach.published_or_final_versio

A real-time monitor using wavelet analysis of the Doppler heart sound for the detection of venous air embolism

A fast detection algorithm for venous air embolism (VAE) was developed and implemented as a real-time monitor for detecting embolic heart sound and estimating embolic air volume. Its performance was evaluated under bolus injection of sub-clinical (0.0l to 0.80 ml) and continuous infusion of clinically significant (0.80 to 9.60 ml) air volumes in anaesthetized dogs. The clinically significant air emboli could be estimated based on the calibration curve obtained during sub-clinical VAE for a subject. The monitor also kept track of the cumulative embolic air volumes and alerted the anaesthetists once a predefined clinically significant embolic air volume was reached. As both humans and dogs share similar physiological conditions, our monitor for dogs are expected to be applicable to humans.published_or_final_versio

Detection and quantification of venous air embolism by wavelet analysis of Doppler heart sound

The wavelet analysis of the Doppler heart sound detected under controlled venous air embolism at sub-clinically and clinically significant volumes was studied in anaesthetized dogs. Signal processing with wavelet enhances the Dower of embolic signal and facilitates the simple detection and extraction of embolic heart beats by thresholding. The cumulative power of the extracted embolic heart beats is found to be linearly related to the volume of embolic air on the log-log scale, suggesting that it is feasible to estimate clinically significant volume of embolic air in human subjects by linearly extrapolating from sub-clinical embolic volumes.published_or_final_versio

When will youth smokers make a quit attempt and resume smoking after receiving telephone counseling? A longitudinal study

Paper Session 10 - Adolescent Smoking Cessation: PA10-1OBJECTIVE: To examine the pattern of youth smokers who received telephone smoking cessation intervention and who would initiate a quit attempt and subsequently resume smoking. METHODS: We collected data from a toll-free smoking cessation hotline “Youth Quitline” in Hong Kong from September 2005 to December 2007. The Youth Quitline is a peer-led hotline with multiple telephone counseling sessions at baseline, 1-week and 1-month and successive telephone follow-ups at 3- and 6-months, to help youth smokers aged 12 – 25 quit smoking. We applied non-parametric Kaplan-Meier method to explore the time trend prior to initiating a quit attempt as well as smoking resumption. RESULTS: The study included 408 youth callers, and 282 started quitting within the follow-up period. About 30% of the youth smokers (95%CI = 26 ￢– 35%) would initiate a quit attempt within 7 days after receiving the baseline telephone intervention. For the 282 callers who quit within the follow-up period, two-thirds (67%, 95%CI = 44 – 56%) resumed smoking within the first 7 days after their quit attempt. CONCLUSIONS: This is the first study using survival analysis techniques to evaluate how soon youth smokers initiate their quit attempts and resume smoking, after receiving telephone counseling. Youth smokers who intend to quit initiate a quit attempt shortly after receiving the telephone intervention. Smoking cessation counselors should provide subsequent follow-ups promptly after the baseline intervention to capitalize on the quitting intentions of the smokers.postprintThe 16th Annual Meeting of the Society for Research on Nicotine and Tobacco (SRNT 2010), Baltimore, MD., 24-27 February 2010. In Proceedings of the SRNT, 2010, p. 2

Tetrandrine, an activator of autophagy, induces autophagic cell death via PKC-α inhibition and mTOR-dependent mechanisms.

Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes. In addition, tetrandrine induces cell death in a panel of apoptosis-resistant cell lines that are deficient for caspase 3, caspase 7, caspase 3 and 7, or Bax-Bak respectively. We also showed that tetrandrine-induced cell death is independent of necrotic cell death. Mechanistically, tetrandrine induces autophagy that depends on mTOR inactivation. Furthermore, tetrandrine induces autophagy in a calcium/calmodulin-dependent protein kinase kinase-β (CaMKK-β), 5′ AMP-activated protein kinase (AMPK) independent manner. Finally, by kinase profiling against 300 WT kinases and computational molecular docking analysis, we showed that tetrandrine is a novel PKC-α inhibitor, which lead to autophagic induction through PKC-α inactivation. This study provides detailed insights into the novel cytotoxic mechanism of an anti-tumor compound originated from the herbal plant, which may be useful in promoting autophagy mediated- cell death in cancer cell that is resistant to apoptosis.published_or_final_versio

Counter-current chromatography for the separation of terpenoids: A comprehensive review with respect to the solvent systems employed

Copyright @ 2014 The Authors.This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Natural products extracts are commonly highly complex mixtures of active compounds and consequently their purification becomes a particularly challenging task. The development of a purification protocol to extract a single active component from the many hundreds that are often present in the mixture is something that can take months or even years to achieve, thus it is important for the natural product chemist to have, at their disposal, a broad range of diverse purification techniques. Counter-current chromatography (CCC) is one such separation technique utilising two immiscible phases, one as the stationary phase (retained in a spinning coil by centrifugal forces) and the second as the mobile phase. The method benefits from a number of advantages when compared with the more traditional liquid-solid separation methods, such as no irreversible adsorption, total recovery of the injected sample, minimal tailing of peaks, low risk of sample denaturation, the ability to accept particulates, and a low solvent consumption. The selection of an appropriate two-phase solvent system is critical to the running of CCC since this is both the mobile and the stationary phase of the system. However, this is also by far the most time consuming aspect of the technique and the one that most inhibits its general take-up. In recent years, numerous natural product purifications have been published using CCC from almost every country across the globe. Many of these papers are devoted to terpenoids-one of the most diverse groups. Naturally occurring terpenoids provide opportunities to discover new drugs but many of them are available at very low levels in nature and a huge number of them still remain unexplored. The collective knowledge on performing successful CCC separations of terpenoids has been gathered and reviewed by the authors, in order to create a comprehensive document that will be of great assistance in performing future purifications. © 2014 The Author(s)