Hybrid opto-chemical doping in Ag nanoparticle-decorated monolayer graphene grown by chemical vapor deposition probed by Raman spectroscopy.

The novel opto-chemical doping effect in Ag nanoparticle-decorated monolayer graphene grown by chemical vapor deposition has been investigated using Raman spectroscopy for the first time. We used both noble metal nanoparticles and optical excitation, in a hybrid opto-chemical route, to tune the doping level in graphene. Metal nanoparticle-induced chemical effects and laser power-induced substrate effects alter the doping nature of graphene from p- to n-type. Compared with earlier studies, the proposed method significantly lowers the laser intensity required for optical power-dependent doping, resulting in prevention of damage to the sample due to local heating. Some other interesting observations are the enhanced peak intensity in the Raman spectrum of graphene, enhancement of the D-band intensity and the introduction of G-band splitting. This novel, cheap and easily implemented hybrid optical-chemical doping strategy could be very useful for tuning graphene plasmons on the widely used Si/SiO2 substrates for various photonic device applications.

The high prevalence of serine protease autotransporters of Enterobacteriaceae (SPATEs) in Escherichia coli causing neonatal septicemia.

Serine protease autotransporters of Enterobacteriaceae (SPATEs) are secreted proteins demonstrating diverse virulence functions. The distribution of SPATEs is studied among diarrheagenic and extraintestinal pathogenic Escherichia coli. However, the contribution of SPATEs to the virulence of neonatal septicemic Escherichia coli (NSEC) has not yet been elucidated. This study was undertaken to evaluate the prevalence and phylogenetic distribution of different subtypes of SPATEs among NSEC. The presence of virulence factors and subtypes of SPATEs among different E. coli isolates was determined by polymerase chain reaction (PCR). E. coli phylogrouping was done by triplex PCR. Clonality of the isolates was assessed by pulsed-field gel electrophoresis (PFGE). The presence of SPATEs was significantly higher among the septicemic isolates (89 %) than the fecal (7.5 %) and environmental isolates (2.5 %). Vat (vacuolating autotransporter toxin) and Sat (secreted autotransporter toxin) were found to be the two most predominant SPATEs. The incidence of SPATEs was high in septicemic isolates of phylogroups A and B1 (87 %), lacking other virulence factors. The high prevalence of SPATEs in the non-B2 phylogroups of septicemic isolates in comparison with fecal and environmental isolates indicates an association of SPATEs with NSEC. The NSEC isolates were found to be clonally distinct, suggesting that the high prevalence of SPATEs was not due to clonal relatedness of the isolates. This study is the first to show the association of SPATEs with NSEC. The presence of SPATEs in the septicemic/NSEC isolates may be considered as the most discriminatory trait studied here.

Dose to Organ at Risk and its Characteristic Variation with the Clinically Used Different Prescription Levels for Early-stage Left-sided Breast Cancer.

AIMS: To evaluate the organ at risk (OAR) dose and its characteristic variation with different clinically usable prescription doses (RxD) for breast and chest wall radiotherapy in patients with early-stage left-sided breast cancer. MATERIALS AND METHODS: In total, 145 patients with early-stage breast cancers (T1N0M0-T2N0M0) on the left side were treated with radiotherapy after a modified radical mastectomy or breast conservation surgery, with a mean age of 45.1 ± 21.6 years. The patient received 4050 cGy of field-in-field (three-dimensional conformal radiotherapy) treatment limited to the breast or chest wall, excluding the supraclavicular node, axillary node and internal mammary chain, over 15 fractions. Additional plans of 5000 cGy/25 fractions, 4500 cGy/20 fractions and 2600 cGy/5 fractions were created with no or minor changes to the original plan. Mathematical modelling was used to study the distinctive change in the dose-volume characteristics for various OARs as a function of the RxD. OAR dosages, both absolute and normalised, were expressed in terms of the RxD. The mathematical (functional) relationship between OAR doses and different prescription levels was deduced by the least squares fit method. RESULT: The left lung mean dose, V5Gy (%), V10Gy (%) and V20Gy (%) and the heart mean dose, V10Gy (%) and V20Gy (%) were evaluated. The dose-volume parameters showed a parabolic variation (x2) with the RxD. Prescription normalised OAR doses showed a linear relationship with the RxD; relative dose increased with diminishing RxD. Normalised lung and heart mean doses exhibited saturation (linear relationship) with RxD variation. Paired sample t-test results between RxD versus all evaluated parameters were found to be statistically significant (P = 0.004). The Pearson correlation coefficient between different prescription levels for left lung mean dose (range 0.942-1.0), heart mean dose (range 1.0-1.0), left lung V5Gy (%) (range 0.987-1.0), left lung V10Gy (%) (range 0.991-0.999), heart V10Gy (%) (range 0.998-1.0). CONCLUSION: The functional form of absolute OAR dose-volume parameters versus RxD is parabolic and the RxD normalised OAR dose-volume parameter versus RxD is a straight line with a negative slope as RxD increases. This indicates an increase in the relative OAR dose-volume parameters if the RxD is reduced. This study is the first of its kind to compare the OAR doses as a function of clinically used degenerate prescription levels. These data will help to comprehend the OAR doses while adopting a new dose fractionation regimen and reviewing the radiotherapy treatment plans.

Effect of a novel microbial phytase on production performance and tibia mineral concentration in broiler chickens given low-calcium diets.

1. In a 42-d feeding trial, 264 one-d-old, as hatched, Cobb 400 broiler chickens (6 pens per group, n = 11 per pen in a 2 × 2 factorial arrangement) were fed on two concentrations of dietary calcium (Ca) (9.0 and 7.5 g/kg in starter, 7.5 and 6 g/kg in grower phases) and supplemental phytase (0 and 500 U/kg diet). 2. During d 0-21, the high Ca + phytase diet improved body weight. During d 0-42, feed intake was increased by the low Ca diet and decreased by phytase supplementation. Feed conversion ratio during d 0-21 was improved by the high Ca + phytase diet. 3. At d 42, Ca in duodenal digesta was reduced by low dietary Ca and supplemental phytase. High dietary Ca reduced P in duodenal and jejunal digesta. Phytase reduced digesta P and increased serum P concentration. 4. Relative tibia length decreased with low dietary Ca and increased with phytase. The robusticity index of tibia was improved by the low Ca diet and phytase supplementation. Phytase supplementation increased tibia ash and concentrations of Ca, magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn) and iron (Fe) in tibia. The low Ca diet increased Mg, Mn and Fe and reduced Cu and Zn in tibia. 5. It was concluded that 7.5 g Ca/kg during weeks 0-3 and 6 g Ca/kg during weeks 3-6 sustained broiler performance and bone ash, while phytase supplementation facilitated tibia mineralisation, particularly during the grower phase.

Improved gas sensing activity in structurally defected bilayer graphene.

Graphene is a two-dimensional material with a capability of gas sensing, which is here shown to be drastically improved by inducing gentle disorder in the lattice. We report that by using a focused ion beam technique, controlled disorder can be introduced into the graphene structure through Ga(+) ion irradiation. This disorder leads to an increase in the electrical response of graphene to NO(2) gas molecules by a factor of three in an ambient environment (air). Ab initio density functional calculations indicate that NO(2) molecules bind strongly to Stone-Wales defects, where they modify electronic states close to the Fermi level, which in turn influence the transport properties. The demonstrated gas sensor, utilizing structurally defected graphene, shows faster response, higher conductivity changes and thus higher sensitivity to NO(2) as compared to pristine graphene.

Assessment of yeast cell wall as replacements for antibiotic growth promoters in broiler diets: effects on performance, intestinal histo-morphology and humoral immune responses.

The study compared the effects of an antibiotic growth promoter (AGP), yeast (Saccharomyces cerevisiae) and yeast cell wall (YCW) on performance, microbiology and histo-morphology of the small intestine and humoral immune responses in Ross 308 broilers. The treatments (eight replicates/treatment, n = 12/replicate) were negative control (NC, without AGP), positive control (PC, supplemented with bacitracin methylene disalicylate, 400 mg/kg), Y and YCW (supplemented with yeast and YCW, respectively, 1000 mg/kg). Live weight at 42 days improved (p = 0.086) in the PC, Y and YCW groups. Feed conversion ratio was better (p = 0.039) in the YCW group compared with the other groups. Antibiotic growth promoter in the PC group shortened the villi in duodenum (p = 0.044). Mucosal Escherichia coli number was higher in the PC group (p < 0.001), whereas in the digesta E. coli number was lower (p = 0.001) in the PC, Y and YCW groups in relation to the NC. Mucosal Salmonella populations increased (p = 0.0001) in the PC group, whereas in the digesta, all treatments reduced the Salmonella (p = 0.0001). Following oral challenge with Salmonella pullorum, YCW increased E. coli numbers on the mucosa (p < 0.001) whereas in the digesta the Y group had lower (p < 0.0001) number of E. coli. In the digesta, Salmonella count was lower in the YCW group compared with the other treatments (p < 0.01). Yeast cell wall -treated birds exhibited better (p < 0.05) humoral immune response against Newcastle disease which was far more persistent over time than in any other treatments. It was concluded that the yeast and the yeast cell wall may have effects identical to BMD on performance of broilers and thus may constitute an effective replacement strategy in the dietary regimens for broiler chickens.

Effects of hydrolysed Saccharomyces cerevisiae yeast and yeast cell wall components on live performance, intestinal histo-morphology and humoral immune response of broilers.

1. The effects of enzymatically hydrolysed whole Saccharomyces cerevisiae yeast (HY) and the pellets of yeast cell wall (YCW) on production traits, the microbiology and histo-morphology of the small intestine, and humoral immune responses against Newcastle disease virus (NDV), of Ross 308 broilers were investigated. 2. The control group received a maize-soyabean meal based basal diet for 42 days. In the treated groups the basal diet was supplemented with 1 g/kg of HY and YCW. There were 8 replicate pens per group (n = 12 birds/pen). 3. HY and YCW supplementation improved live weight (P = 0·006) and FCR (P = 0·003) at 42-d as compared with the control group. 4. In the small intestine, Salmonella spp and Escherichia coli numbers were higher (P = 0·01) in the mucosa and lower (P = 0·01) in the digesta of the HY and the YCW fed groups at 25 d of age. Lactobacillus in the duodenal and jejunal digesta was higher (P < 0·05) in the HY and the YCW fed groups as compared with the control. 5. Following oral challenge with Salmonella pullorum, Escherichia coli and Lactobacillus increased (P < 0·05) in the mucosa and decreased in the digesta (P < 0·05) of the HY and YCW supplemented groups, relative to the control. 6. Supplementation of HY and YCW increased villus height in the jejunum (P = 0·02), width of villus in the ileum (P = 0·034) and number of goblet cells in villi of the jejunum (P = 0·006) and ileum (P = 0·01). 7. YCW increased antibody level against NDV at 21 and 42 d of age compared with the control and the HY supplemented diets (P < 0·05). 8. It was concluded that HY and YCW improved growth and feed efficiency in broilers, and considering the improvements in production traits and humoral immune responses, yeast cell wall may be a better dietary tool than the hydrolysed whole yeast cell as a performance enhancer for broilers.

Development of simple and rapid PCR-fingerprinting methods for Vibrio cholerae on the basis of genetic diversity of the superintegron.

AIMS: To develop simple and rapid PCR-fingerprinting methods for Vibrio cholerae O1 (El Tor and classical biotypes) and O139 serogroup strains which cause major cholera epidemics, on the basis of the diversity of superintegron (SI) carried by these strains. METHODS AND RESULTS: PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed targeting region between integrase gene in the SI and its nearby ORF, followed by BglI digestion. Besides, a V. cholerae repeat-amplified fragment length polymorphism (VCR-AFLP) assay was also developed. In the PCR-RFLP, 94 El Tor, 29 classical and 54 O139 strains produced nine, three and six different DNA fingerprints, respectively. On the other hand, VCR-AFLP distinguished these El Tor, classical and O139 strains into five, nine and two DNA fingerprints, respectively. Combining both assays the El Tor, classical and O139 strains could be differentiated into 11, 10 and seven different types, respectively. In a comparative study, pulsed-field gel electrophoresis (PFGE) showed similar differentiation for El Tor (11 types), but lower discrimination for O139 (two types) and classical strains (five types). CONCLUSIONS: The PCR assays based on SI diversity can be used as a useful typing tool for epidemiological studies of V. cholerae. SIGNIFICANCE AND IMPACT OF STUDY: This newly developed method is more discriminatory, simple, rapid and cost-effective in comparison with PFGE, and thus can be widely applicable.

A highly sensitive and specific multiplex PCR assay for simultaneous detection of Vibrio cholerae, Vibrio parahaemolyticus and Vibrio vulnificus.

AIMS: To develop an effective multiplex PCR for simultaneous and rapid detection of Vibrio cholerae, Vibrio vulnificus and Vibrio parahaemolyticus, the three most important Vibrio species that can cause devastating health hazards among human. METHODS AND RESULTS: Species-specific PCR primers were designed based on toxR gene for V. cholerae and V. parahaemolyticus, and vvhA gene for V. vulnificus. The multiplex PCR was validated with 488 Vibrio strains including 322 V. cholerae, 12 V. vulnificus, and 82 V. parahaemolyticus, 20 other Vibrio species and 17 other bacterial species associated with human diseases. It could detect the three target bacteria without any ambiguity even among closely related species. It showed good efficiency in detection of co-existing target species in the same sample. The detection limit of all the target species was ten cells per PCR tube. CONCLUSIONS: Specificity and sensitivity of the multiplex PCR is 100% each and sufficient for simultaneous detection of these potentially pathogenic Vibrio species in clinical and environmental samples. SIGNIFICANCE AND IMPACT OF THE STUDY: This simple, rapid and cost-effective method can be applicable in a prediction system to prevent disease outbreak by these Vibrio species and can be considered as an effective tool for both epidemiologist and ecologist.

Development of a haemolysin gene-based multiplex PCR for simultaneous detection of Vibrio campbellii, Vibrio harveyi and Vibrio parahaemolyticus.

AIM: To develop a haemolysin (hly) gene-based species-specific multiplex PCR for simple and rapid detection of Vibrio campbellii, V. harveyi and V. parahaemolyticus. METHODS AND RESULTS: The complete hly genes of three V. campbellii strains isolated from diseased shrimps were sequenced and species-specific PCR primers were designed based on these sequences and the registered hly gene sequences of Vibrio harveyi and Vibrio parahaemolyticus. Specificity and sensitivity of the multiplex PCR was validated with 27 V. campbellii, 16 V. harveyi, and 69 V. parahaemolyticus, 18 other Vibrio species, one Photobacterium damselae and nine other bacterial species. The detection limits of all the three target species were in between 10 and 100 cells per PCR tube. CONCLUSIONS: Specificity and sensitivity of the multiplex PCR is 100% each and sufficient to be considered as an effective tool in a prediction system to prevent potential disease outbreak by these Vibrio species. SIGNIFICANCE AND IMPACT OF THE STUDY: Because there is lack of simple, rapid and cost-effective method to differentiate these closely related V. campbellii, V. harveyi and V. parahaemolyticus species, the multiplex PCR developed in this study will be very effective in epidemiological, ecological and economical points of view.

Brown fat activity determined by infrared thermography and thermogenesis measurement using whole body calorimetry (BRIGHT Study).

To assess BAT activity in humans at a population level, infrared thermography (IRT) represents a safe, readily repeatable and affordable alternative to 18F-FDG-PET. Building upon a previously proposed method by our laboratory, we further refined the image computational algorithm to quantify BAT activation in the cervical-supraclavicular (C-SCV) region of healthy young men under thermo-neutral and cold exposure conditions. Additionally, we validated the whole-body calorimeter (WBC) in reliably measuring cold-induced thermogenesis. The temperature gradient between C-SCV-deltoid regions, and the corresponding difference in heat power output, increased upon cold air exposure relative to thermo-neutral conditions (by 74.88 %, p<0.0001; and by 71.34 %, p<0.0001 respectively). Resting and cumulative energy expenditure (EE) rose significantly (by 13.14 % and 9.12 % respectively, p=0.0001) while positive correlations between IRT measures and EE were found with cold air exposure (percentage change in heat power gradient between ROI and deltoid, cold air: r(2)=0.29, p=0.026, Pearson's correlation). IRT and WBC can be used to study BAT activation. The refined algorithm allows for more automation and objectivity in IRT data analysis, especially under cold air exposures.

Production and carcase traits in broiler chickens given diets supplemented with inorganic trivalent chromium and an organic acid blend.

1. The study was conducted to ascertain the effects of supplemental organic acids and chromium (Cr) on production and carcase traits of broiler chickens. 2. A total of 120 1-d-old broiler chicks were divided into 4 treatment groups in a 2 x 2 factorial design (each treatment group contained 6 replicates with 5 birds per replicate). 3. The diets were supplemented with an organic acid blend containing ortho-phosphoric, formic and propionic acid and calcium propionate (1 g/kg diet) and inorganic trivalent chromium (Cr(3+)) as chromic chloride hexahydrate (0.5 mg/kg diet) either independently or together as a combination for 35 d. 4. Individual supplementation of organic acids and Cr(3+) and their combination significantly improved the food conversion ratio, hot and dressed carcase weight and weight of the wholesale cuts compared to the control group of birds. 5. Organic acids, either independently or along with Cr(3+), increased total accretion of ash in carcase. Protein accretion was improved by dietary Cr(3+) and organic acid supplementation compared to the control group and a further improvement in this regard was observed when Cr(3+) and organic acid were supplemented together. Across the treatment groups meat fat content and fat accretion were lower in birds receiving dietary Cr(3+) supplementation. 6. Circulatory Cr(3+) and meat Cr(3+) concentration increased compared to the other treatment groups when Cr(3+) was supplemented to the birds. 7. It was concluded that, instead of individual supplementation, a combination of Cr(3+) and organic acids may improve the production and carcase traits of broilers more effectively presumably because of an additive effect.

Castlemans disease in HIV infected patient from eastern India.

Castlemans disease is a rare lymphoproliferative disorder. We report a patient of Castlemans disease with advanced HIV infection who responded well to conventional HAART. This case is interesting because of the rarity of the disease in the eastern part of India and its good out come with antiretroviral therapy.

A potential role for interleukin-15 in the regulation of human natural killer cell survival.

Resting lymphocyte survival is dependent upon the expression of Bcl-2, yet the factors responsible for maintaining lymphocyte Bcl-2 protein expression in vivo are largely unknown. Natural killer (NK) cells are bone marrow-derived lymphocytes that constitutively express the beta and common gamma(c) subunits of the IL-2 receptor (R) as a heterodimer with intermediate affinity for IL-2. IL-15 also binds to IL-2Rbeta gamma(c) and is much more abundant in normal tissues than IL-2. Mice that lack the IL-2 gene have NK cells, whereas mice and humans that lack IL-2R gamma(c) do not have NK cells. Further, treatment of mice with an antibody directed against IL-2Rbeta results in a loss of the NK cell compartment. These data suggest that a cytokine other than IL-2, which binds to IL-2Rbeta gamma(c), is important for NK cell development and survival in vivo. In the current report, we show that the recently described IL-15R(alpha) subunit cooperates with IL-2Rbeta gamma(c) to transduce an intracellular signal at picomolar concentrations of IL-15. We demonstrate that resting human NK cells express IL-15R(alpha) mRNA and further, that picomolar amounts of IL-15 can sustain NK cell survival for up to 8 d in the absence of serum. NK cell survival was not sustained by other monocyte-derived factors (i.e., TNF-alpha, IL-1beta, IL-10, IL-12) nor by cytokines known to use gamma(c) for signaling (i.e., IL-4, IL-7, IL-9, IL- 13). One mechanism by which IL-15 promotes NK cell survival may involve the maintenance of Bcl-2 protein expression. Considering these functional properties of IL-15 and the fact that it is produced by bone marrow stromal cells and activated monocytes, we propose that IL-15 may function as an NK cell survival factor in vivo.

Complementation by BCL2 and C-HA-RAS oncogenes in malignant transformation of rat embryo fibroblasts.

The BCL2 (B cell lymphoma/leukemia-2) and C-HA-RAS oncogenes encode membrane-associated proteins of 26 and 21 kilodaltons, respectively. Although RAS proteins have long been known for their ability to bind and hydrolyze GTP, recent investigations suggest that BCL2 encodes a novel GTP-binding protein (S. Haldar, C. Beatty, Y. Tsujimoto, and C. M. Croce, Nature [London] 342:195-198, 1989). Cotransfection of BCL2 and HA-RAS oncogenes resulted in morphological transformation of early-passage rodent fibroblasts, rendering these cells tumorigenic in animals and enabling them to grow in semisolid medium. In contrast, cotransfection of BCL2 with oncogenes that encode nuclear proteins (E1A and C-MYC) did not produce malignant transformation, whereas HA-RAS did complement with these genes. These findings suggest that proteins encoded by oncogenes such as BCL2 and HA-RAS, although having similar subcellular locations and perhaps similar biochemical properties, can regulate distinct complementary pathways involved in cellular transformation.

Influence of habitual diet on antioxidant status: a study in a population of vegetarians and omnivores.

BACKGROUND: Antioxidant status can be used as a biomarker to assess chronic disease risk and diet can modulate antioxidant defence. OBJECTIVE: To examine effects of vegetarian diet and variations in the habitual intakes of foods and nutrients on blood antioxidants. SUBJECTS AND SETTING: Thirty-one vegetarians (including six vegans) and 58 omnivores, non-smokers, in Northern Ireland. DESIGN: A diet history method was used to assess habitual diet. Antioxidant vitamins, carotenoids, uric acid, zinc- and ferric-reducing ability of plasma (FRAP) were measured in fasting plasma and activities of glutathione peroxidase (GPX), superoxide dismutase (SOD) and glutathione S-transferase (GST) and level of reduced glutathione (GSH) were measured in erythrocytes. RESULTS: Vegetarians had approximately 15% higher levels of plasma carotenoids compared with omnivores, including lutein (P< or =0.05), alpha-cryptoxanthin P< or =0.05), lycopene (NS), alpha-carotene (NS) and beta-carotene (NS). The levels/activities of all other antioxidants measured were similar between vegetarians and omnivores. Total intake of fruits, vegetables and fruit juices was positively associated with plasma levels of several carotenoids and vitamin C. Intake of vegetables was positively associated with plasma lutein, alpha-cryptoxanthin, alpha-carotene and beta-carotene, whereas intake of fruits was positively associated with plasma beta-cryptoxanthin. Intake of tea and wine was positively associated with FRAP value, whereas intake of herbal tea associated positively with plasma vitamin C. Intakes of meat and fish were positively associated with plasma uric acid and FRAP value. CONCLUSIONS: The overall antioxidant status was similar between vegetarians and omnivores. Good correlations were found between intakes of carotenoids and their respective status in blood.

Effect of carrier confinement on effective mass of excitons and estimation of ultralow disorder in Al x Ga1-x As/GaAs quantum wells by magneto-photoluminescence.

Effect of charge carrier confinement and ultra-low disorder acquainted in AlGaAs/GaAs multi-quantum well system is investigated via Magneto-photoluminescence spectroscopy. Significant increase of effective mass is observed for the confined exciton in narrow QWs. The foremost reason behind such an observation is due to the induced non-parabolicity in bands. Moreover, as the thickness of the QW are reduced, confined excitons in QW experience atomic irregularities at the hetero-junctions and their effects are prominent in the photoluminescence linewidth. Amount of photoluminescence line-broadening caused by the atomic irregularities at the hetero-junctions is correlated with average fluctuation (δ 1) in QW thickness. The estimated δ 1 for Al0.3Ga0.7As/GaAs QWs are found to be ±(0.14 - 1.6)× 'one monolayer thickness of GaAs layer'. Further, the strong perturbations due to magnetic field in a system helps in realizing optical properties of exciton in QWs, where magnetic field is used as a probe to detect ultralow defects in the QW. Additionally, the influence of magnetic field on the free and bound exciton luminescence is explained by a simple model. The proposed approach for measuring the interface and volume defects in an ultra-low disordered system by Magneto-PL spectroscopy technique will be highly beneficial in high mobility devices for advanced applications.

Juvenile idiopathic arthritis.

This study attempts to determine the clinical manifestations, severity and immunological features of JIA and its influence on growth and associated cardiac involvement in children below 16 years of age. This is a cross sectional study in a tertiary referral center on 50 consecutive children below the age of 16 years. Each patient was thoroughly examined and scored on Juvenile Arthritis Functional Assessment Scale. Relevant blood tests, cardiac and ophthalmic evaluation was done. Growth patterns were noted. There was an overall equal sex ratio, though there was a male preponderance in the systemic and oligoarthritis groups. Disturbance of growth frequently occurred in children suffering from JIA. Cardiac involvement should be looked for in cases of JIA. Significant number of cases of PSRA is diagnosed in children presenting with chronic arthritis.

Bcl2 is the guardian of microtubule integrity.

We have investigated the ability of several drugs commonly used in the treatment of human cancer to induce bcl2 phosphorylation and cell death in human cell lines derived from acute leukemia, lymphoma, breast cancer, and prostate cancer. The results of this analysis indicate that drugs affecting the integrity of microtubules induce bc12 phosphorylation, whereas anticancer drugs damaging DNA do not. Comparison of the effects of taxol and its analogue, taxotere, indicates that taxotere is capable of inducing bcl2 phosphorylation and apoptotic cell death at 100-fold lower concentrations than taxol. Induction of cancer cell death through phosphorylation of bcl2 thus provides an opportunity not only for more refined targeting of therapeutic drugs but for understanding of an important pathway leading to apoptosis. Phosphorylation of bcl2 in drug-treated cancer cells occurs in G2-M, the phase of the cell cycle in which this class of drugs is active. No induction of bcl2 phosphorylation occurs in chronic lymphocytic leukemia cells that overexpress bcl2 but are blocked at G0-G1. Thus, prevention of polymerization or depolymerization of cellular microtubules by this class of cancer therapeutic drugs causes phosphorylation of bcl2, abrogating the normal antiapoptotic function of bcl2 and initiating the apoptotic program in the cycling cancer cells; these results are consistent with a normal physiological role of bcl2 as "guardian of microtubule integrity."