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Development of drugs targeting Bcl-2 relatives and caspases, for treating diseases including cancer and inflammatory disorders, often involves measuring interactions with recombinant target molecules, and/or monitoring cancer cell killing in vitro. Here, we present yeast-based methods for evaluating drug-mediated inhibition of Bcl-2 relatives or caspases. Active Bax and caspases kill Saccharomyces cerevisiae, and pro-survival Bcl-2 proteins can inhibit Bax-induced yeast death. By measuring the growth or adenosine triphosphate content of transformants co-expressing Bax with pro-survival Bcl-2 relatives, we found that the Bcl-2 antagonist drugs ABT-737 or ABT-263 abolished Bcl-2 or Bcl-xL function and reduced Bcl-w activity, but failed to inhibit Mcl-1, A1 or the poxvirus orthologs DPV022 and SPPV14. Using this technique, we also demonstrated that adenoviral E1B19K was resistant to these agents. The caspase inhibitor Q-VD-OPh suppressed yeast death induced by caspases 1 and 3. Yeast engineered to express human apoptotic regulators enable simple, automatable assessment of the activity and specificity of candidate drugs targeting Bcl-2 relatives or caspases.

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Chronic inflammation in ankylosing spondylitis (AS) is associated with vascular endothelial dysfunction. Infliximab improves inflammatory disease activity in AS patients, but its effect on endothelial dysfunction has still not been tested in these patients. Twelve anti-TNF naive AS patients (mean age, 32.6 +/- 3.94 years; disease duration, 5.6 +/- 0.8 years) with high disease activity [Bath ankylosing spondylitis disease activity index (BASDAI score > 4)] despite treatment with stable doses of conventional disease modifying anti-rheumatic drugs (DMARDs) were investigated. Inflammatory disease activity [BASDAI and Bath ankylosing spondylitis functional index (BASFI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels], serum nitrite concentration, and endothelium-dependent and endothelium-independent vasodilation of the brachial artery were measured at baseline and 12 weeks of therapy after single intravenous infusion of infliximab (5 mg/kg). Previous DMARD(s) regimen remained unchanged throughout the study period. After treatment with infliximab, flow-mediated vasodilation improved from 9.81 +/- 1.70% to 26.93 +/- 2.34% (p < 0.001), whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter (13.65 +/- 2.10% versus 14.59 +/- 1.93%, p = 0.08, and 4.45 +/- 0.15 versus 4.46 +/- 0.15 mm, p = 0.3, respectively). Nitrite concentration reduced from 6.50 +/- 0.21 to 2.57 +/- 0.18 micromol/l (p < 0.001), ESR from 40.90 +/- 6.00 to 11.50 +/- 1.38 mm in the first hour (p < 0.001), and CRP level from 29.08 +/- 4.11 to 2.69 +/- 0.43 mg/dl (p < 0.001). BASDAI and BASFI scores were significantly reduced from 5.40 +/- 1.14 to 1.40 +/- 0.70 (p < 0.05) and 5.05 +/- 1.76 to 0.20 +/- 0.63 (p < 0.05), respectively. The study suggests that in ankylosing spondylitis, endothelial dysfunction is a part of the disease process and infliximab improves both endothelial dysfunction and inflammatory disease activity.

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OBJECTIVE: Chronic inflammation in rheumatoid arthritis (RA) is associated with vascular endothelial dysfunction. The aim of this study was to determine the effect of spironolactone on endothelial function in anti-tumour necrosis factor (TNF)-naive RA patients. METHODS: Twenty-four anti-TNF-naive RA patients (mean age 49 +/- 1.8 years; disease duration 8.5 +/- 5.8 years) with high disease activity [Disease Activity Score including a 28-joint count (DAS28 > 5.1)] despite treatment with stable doses of conventional disease-modifying anti-rheumatic drugs (DMARDs) were investigated. Inflammatory disease activity [DAS28 and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)], serum markers of endothelial dysfunction, serum nitrite concentration, and endothelium-dependent and -independent vasodilation of the brachial artery were measured before and after 12 weeks of therapy with oral spironolactone 2 mg/kg/day. RESULTS: After treatment with spironolactone, flow-mediated vasodilation (FMD) improved from 3.18 +/- 0.46% to 3.95 +/- 0.49% (p < 0.001) whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter (18.4 +/- 1.15% vs. 18.3 +/- 1.13%, p = 0.046, and 3.5 +/- 0.1 vs. 3.52 +/- 0.1 mm, p = 0.952, respectively); serum nitrite concentration was reduced significantly from 6.9 +/- 0.34 to 6.8 +/- 0.33 micromol/L (p < 0.001), ESR from 59.90 +/- 4.86 to 51.22+/-4.26 mm in the first hour (p < 0.001), and CRP level from 15.2+/-3.8 to 9.4+/-2.6 mg/dL (p = 0.019). DAS28 and HAQ-DI scores were significantly reduced, from 6.9+/-0.25 to 4.1+/-0.31 (p < 0.05) and from 1.47+/-0.09 to 0.69+/-0.1 (p < 0.05), respectively. CONCLUSIONS: The study suggests that, in RA, endothelial dysfunction is part of the disease process and treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity in RA.

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In this paper, an efficient technique for compression of medical ultrasound (US) images is proposed. The technique is based on wavelet transform of the original image combined with vector quantization (VQ) of high-energy subbands using the LBG algorithm. First, we analyse the statistical behaviour of wavelet coefficients in US images across various subbands and scales. The analysis show that most of the image energy is concentrated in one of the detail subband, either in the vertical detail subband (most of the time) or in the horizontal subband. The other two subbands at each decomposition level contribute negligibly to the total image energy. Then, by exploiting this statistical analysis, a low-complexity image coder is designed, which applies VQ only to the highest energy subband while discarding the other detail subbands at each level of decomposition. The coder is tested on a series of abdominal and uterus greyscale US images. The experimental results indicate that the proposed method clearly outperforms the JPEG2000 (Joint Photographers Expert Group) encoder both qualitatively and quantitatively. For example, without using any entropy coder, the proposed method yields a peak signal to noise ratio gain of 0.2 dB to 1.2 dB over JPEG2000 on medical US images.

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This paper introduces a simple and efficient technique for compression of medical ultrasound (US) images in the wavelet domain. The statistics of subband wavelet coefficients are modelled using the generalized Gaussian distribution (GGD). By exploiting these statistics, a uniform scalar quantizer is designed which adapts very well to the changing statistics of the signal across various subbands and scales. To increase the quantization performance, a threshold is chosen adaptively to zero-out the insignificant wavelet coefficients in the detail subbands before quantization. A distinctive feature of the proposed technique is that it unifies the two approaches to image adaptive coding: rate-distortion (R-D) optimized quantizer selection and R-D optimal thresholding, in order to increase the compression performance of the coder. The operational R-D criterion used for joint optimization is derived in the minimum description length (MDL) framework. The experimental results show that the joint R-D optimization leads to significant improvement in the compression performance of the proposed coder, named JTQ-WV, over the best state-of-the-art image coder, SPIHT. For example, the coding of US images at 0.25 bpp by JTQ-WV yields a PSNR gain of 1.0 dB over the benchmark SPIHT.

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This paper proposes some modifications to the state-of-the-art Set Partitioning In Hierarchical Trees (SPIHT) image coder based on statistical analysis of the wavelet coefficients across various subbands and scales, in a medical ultrasound (US) image. The original SPIHT algorithm codes all the subbands with same precision irrespective of their significance, whereas the modified algorithm processes significant subbands with more precision and ignores the least significant subbands. The statistical analysis shows that most of the image energy in ultrasound images lies in the coefficients of vertical detail subbands while diagonal subbands contribute negligibly towards total image energy. Based on these statistical observations, this work presents a new modified SPIHT algorithm, which codes the vertical subbands with more precision while neglecting the diagonal subbands. This modification speeds up the coding/decoding process as well as improving the quality of the reconstructed medical image at low bit rates. The experimental results show that the proposed method outperforms the original SPIHT on average by 1.4 dB at the matching bit rates when tested on a series of medical ultrasound images. Further, the proposed algorithm needs 33% less memory as compared to the original SPIHT algorithm.

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The paper addresses the problem of how the spatial quantisation mode and subband adaptive uniform scalar quantiser can be jointly optimised in the minimum description length (MDL) framework for compression of ultrasound images. It has been shown that the statistics of wavelet coefficients in the medical ultrasound (US) image can be better approximated by the generalised Student t-distribution. By combining these statistics with the operational rate-distortion (RD) criterion, a space-frequency quantiser (SFQ) called the MDL-SFQ was designed, which used an efficient zero-tree quantisation technique for zeroing out the tree-structured sets of wavelet coefficients and an adaptive scalar quantiser to quantise the non-zero coefficients. The algorithm used the statistical 'variance of quantisation error' to achieve the different bit-rates ranging from near-lossless to lossy compression. Experimental results showed that the proposed coder outperformed the set partitioning in hierarchical trees (SPIHT) image coder both quantitatively and qualitatively. It yielded an improved compression performance of 1.01 dB over the best zero-tree based coder SPIHIT at 0.25 bits per pixel when averaged over five ultrasound images.

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Fetal diastematomyelia is a rare form of spinal dysraphism that is characterized by a complete or incomplete division of the spinal cord by an osseous or fibrocartilaginous septum. A case of diastematomyelia, which was detected on the routine third trimester detailed ultrasound scan, is presented. The diagnosis was based on the detection of an echogenic focus in the posterior aspect of the spine in association with widening of the interpedicular vertebral space. The case illustrates that diastematomyelia can occur in the absence of overt spina bifida and that prenatal detection will allow timely postnatal investigation and treatment. Prenatal literature is further reviewed to assess the clinical significance of this finding.

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Compounds possessing antimutagenic properties (polyphenols, tannins, vitamins, etc.) have been identified in fruits, vegetables, spices, and medicinal plants. Terminalia arjuna (Combretaceae), a tropical woody tree occurring throughout India and known locally as Kumbuk, is a medicinal plant rich in tannins and triterpenes that is used extensively in Ayurvedic medicine as a cardiac tonic. The aim of the present collaborative work was to test six solvent extracts from the bark of Terminalia arjuna for antigenotoxic activity using in vitro short-term tests. Terminalia arjuna extracts were obtained by sequential extraction using acetone, methanol, methanol + HCl, chloroform, ethyl acetate, and ethyl ether. The antigenotoxic properties of these extracts were investigated by assessing the inhibition of genotoxicity of the directacting mutagen 4-nitroquinoline-N-oxide (4NQO) using the "comet" assay and the micronucleus (MN) test. Human peripheral blood leukocytes were incubated with different concentrations of the six extracts (from 5 to 100 microg/ mL) and with 4NQO (1 and 2 microg/mL, for the "comet" assay and MN test, respectively). Each extract/4NQO combination was tested twice; in each experiment, positive control (4NQO alone) and negative control (1% DMSO) were set. "Comet" assay results showed that acetone and methanol extracts were highly effective in reducing the DNA damage caused by 4NQO, whereas the acidic methanol, chloroform, ethyl acetate, and ethyl ether extracts showed less marked or no antigenotoxic activity. In the MN test, a decrease in 4NQO genotoxicity was observed by testing this mutagen in the presence of acetone, methanol, chloroform, and ethyl acetate extracts, even though the extent of inhibition was not always statistically significant.

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The relationship between stressful family life events and somatic complaints in 477 school children was studied. There was a significant association between life events and somatic complaints, with a general trend for somatic complaints to increase in almost direct proportion to the number of family life events. Overall occurrence of these nonspecific symptoms was more in girls. The somatic complaints were significantly more in children from nuclear families and of illiterate or poorly educated mothers. No significant association was observed between somatic complaints and number of children in the family or socio-economic status. Assessment of psychodevelopmental tasks and family environment during routine check up of children by the school health teams and their appropriate training in this field should be stressed upon.

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One hundred children with enuresis were studied to find out various factors responsible for this condition. Enuresis was more frequent in first born, service class and bottle fed children. There was a significant role of stress factors in causation of enuresis. We found a higher frequency of behavioral symptoms among children with enuresis. There was no significant correlation between enuresis and sex, education of parents, social class, sleep patterns, age of mother at marriage and intellectual grades of the children. Worm infestations, giardiasis, amebiasis and urinary infection were seen in 70% of cases. General body weakness, cold and nervousness were the common causes of enuresis in the parents' opinion. The main reason for not seeking the treatment at an early stage in view of parents' was that they thought enuresis a normal variant.

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