\n\nMATERIALS AND METHODS: All the synthesized selleck chemicals compounds 7-12 were tested for their in vitro antifungal activities against Candida sp. namely Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, Candida dubliniensis and Candida krusei.\n\nRESULTS: A close inspection of the in vitro anticandidal activity profile in differently electron withdrawing (-F, -Cl, and -Br) functional group and electron donating (CH3 and OCH3) substituted phenyl rings of novel highly functionalized bis cyclohexenone ethyl carboxylates 7-12 exerted strong anticandidal activity against all the tested Candida species. All the synthesized

compounds 7-12 exhibited MIC value in the range of 6.25-200 mu g/mL against all the tested Candida (C.) species.\n\nCONCLUSIONS: Compound 8 against C. albicans, 9,11 against C. glabrata, 8,10 against C. parapsilosis, 7,9 against C. dubliniensis, 8,10 against C. krusei exhibited excellent anticandidal activity at a MIC value of 6.25 mu g/mL. Likewise compound 7, 911 against C. albicans, 8, 9, buy Buparlisib 11 against C. tropicalis, 8 against C. glabrata, 9 against C. parapsilosis, 10 against C. dubliniensis, 9 against C. krusei revealed superior activity at a MIC value

of 12.5 mu g/mL.”
“A smart fully automated system is proposed for determination of thorium and uranium in a wide concentration range, reaching environmental levels. The hyphenation of lab-on-valve (LOV) and multisyringe flow injection analysis (MSFIA), coupled to a long path length liquid waveguide capillary cell, allows the spectrophotometric determination of thorium and uranium in different types of environmental sample matrices achieving high selectivity and sensitivity levels. Online separation and preconcentration of thorium and uranium is carried out by means of Uranium and TEtraValents Actinides resin. The potential of the LOV-MSFIA makes possible the

full automation of the system by Histone Methyltransf inhibitor the in-line regeneration of the column and its combination with a smart methodology is a step forward in automation. After elution, thorium(IV) and uranium(VI) are spectrophotometrically detected after reaction with arsenazo-III. We propose a rapid, inexpensive, and fully automated method to determine thorium(IV) and uranium(VI) in a wide concentration range (0-1,200 and 0-2,000 mu g L(-1) Th and U, respectively). Limits of detection reached are 5.9.g L(-1) of uranium and 60 eta g L(-1) of thorium. Different water sample matrices (seawater, well water, freshwater, tap water, and mineral water), and a channel sediment reference material which contained thorium and uranium were satisfactorily analyzed with the proposed method.

A standardized list of behaviors was recorded as observed or absent for both conditions with each dog serving as its own control. To calculate the agreement of individual behaviors between the two conditions, Cohen’s Kappa was used. However, since many of the behaviors occurred at very low or high-frequency-rates, Prevalence-Adjusted, Bias-Adjusted Kappa (PABAK) was used along with Cohen’s

Kappa Elafibranor due to Cohen’s Kappa’s sensitivity to high or low prevalence, for which PABAK adjusts. For the purposes of this study, PABAK or Kappa scores greater than 0.61 were considered an indicator of a good degree of agreement between reactions toward the fake and the real dogs. The degree of agreement varied widely across individual behaviors with, Kappa ranging from -0.04 to 0.75 and PABAK from 0.29 to I. Collapsing individual behaviors into behavior traits (e.g., friendly, aggressive, fearful) revealed a high degree of agreement for the friendly trait (Kappa = 0.60, PABAK = 0.69). However, the aggressive trait did not demonstrate adequate agreement (Kappa = 0.11 and PABAK = 0.38) and the fearful trait demonstrated only moderate agreement between the two stimulus conditions (Kappa = 0.50 and

PABAK = 0.51). These results suggest that, while it may be ACY-738 molecular weight possible to use a fake dog for the dog-to-dog subtest to assess friendly behavior toward other dogs, fearful and aggressive behaviors may not be consistent between the fake and real dogs, thus limiting the usefulness of the fake dog during behavior evaluations. In addition, the results of this study suggest more research is needed into the predictive validity of both fake and real

dogs, since it appears the stimulus dog, whether fake or real, can influence the subtest’s results. (C) 2014 Elsevier B.V. All rights reserved.”
“Adjacent alternative 3′ splice sites, those separated by smaller than = 18 nucleotides, provide a unique problem in the study of alternative splicing regulation; there is overlap of the cis-elements that define the adjacent sites. Identification of the intron’s 3′ end depends upon sequence elements that define the branchpoint, polypyrimidine tract, and terminal AG dinucleotide. Starting with RNA-seq data Nutlin-3 price from germline-enriched and somatic cell-enriched Caenorhabditis elegans samples, we identify hundreds of introns with adjacent alternative 3′ splice sites. We identify 203 events that undergo tissue-specific alternative splicing. For these, the regulation is monodirectional, with somatic cells preferring to splice at the distal 3′ splice site (furthest from the 5′ end of the intron) and germline cells showing a distinct shift toward usage of the adjacent proximal 3′ splice site (closer to the 5′ end of the intron). Splicing patterns in somatic cells follow C. elegans consensus rules of 3′ splice site definition; a short stretch of pyrimidines preceding an AG dinucleotide.

By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N-2 adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 +/- 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that

during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. EVP4593 inhibitor Low-temperature nitrogen adsorption-desorption

results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 +/- 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 +/- 0.23%. The drug LBH589 Epigenetics inhibitor sustained-release time was 10 h in selleckchem simulated intestinal fluid and the maximum cumulative released amount was 62.05 +/- 0.13%.

The prepared MCM-41 is a well-controlled drug delivery carrier.”
“A number of states in the United States have laws restricting drivers from using cellphones. Using state-level panel data, we examined the effect of cellphone laws on fatal crashes in the United States between 2000 and 2010. Our results show that there is insufficient power to detect a reduction in overall fatal crash rates scaled by vehicle miles and population estimates. Cellphone bans, however, have significantly reduced the fatal crash rates of drivers in certain age cohorts. The effect was most pronounced among drivers between 18 and 34 years of age. We did not find any significant effect among drivers in the 55 and older age cohorts.”
“May-Thurner syndrome results from long-standing compression of the left common iliac vein (LCIV) and is characterized by the formation of intraluminal spurs leading to obstruction of blood flow and deep vein thrombosis (DVT). Increased intraluminal pressures may occur as a consequence of venous obstruction, which when coupled with other factors thought to further weaken venous wall integrity (ie, inflammation or hormonal imbalances) may produce spontaneous (nontraumatic) and potential lethal venous rupture.

The incidence of postoperative MRSA infections in the MRSA-positive and MRSA-negative groups were compared, and various risk factors for MRSA infections were evaluated. The incidence of postoperative MRSA infections, such as pneumonia and enteritis, in the MRSA-positive group was significantly higher than that in the MRSA-negative group (41.9 vs. 3.1 %). The significant

independent risk factors for postoperative MRSA infections were a positive MRSA screening, an operation lasting more than 300 min and an emergency operation. A positive MRSA screening was the most statistically significant risk factor for postoperative MRSA pneumonia and enteritis, but was not a risk factor for MRSA surgical site infections. Nasal MRSA screening can help to identify patients who have an increased risk of developing postoperative MRSA infections, and would enable physicians to take a prompt action if these complications occur.”
“Preeclampsia selleck compound (PE) is an extremely serious condition in pregnant women and the leading cause of Epigenetics inhibitor maternal and fetal morbidity and mortality. Despite active research, the etiological factors of this disorder remain elusive. The increased release of 15-hydroxyeicosatetraenoic acid (15-HETE) in the placenta of preeclamptic patients has been studied, but its exact role in PE pathogenesis remains unknown. Mounting evidence shows that PE is associated with placental hypoxia, impaired placental angiogenesis, and endothelial

dysfunction. In this study, we confirmed the upregulated expression of hypoxiainducible factor 1 alpha (HIF-1 alpha) and 15-lipoxygenase-1/2 (15-LO-1/2) in patients with PE. Production of the arachidonic acid metabolite, 15-HETE, also increased Z-DEVD-FMK chemical structure in the preeclamptic placenta, which suggests enhanced activation of the HIF-1 alpha-15-LO-15-HETE

axis. Furthermore, this study is the first to show that the umbilical cord of preeclamptic women contains significantly higher serum concentrations of 15-HETE than that of healthy pregnant women. The results also show that expression of 15-LO-1/2 is upregulated in both human umbilical vein endothelial cells (HUVECs) collected from preeclamptic women and in those cultured under hypoxic conditions. Exogenous 15-HETE promotes the migration of HUVECs and in vitro tube formation and promotes cell cycle progression from the G0/G1 phase to the G2/M + S phase, whereas the 15-LO inhibitor, NDGA, suppresses these effects. The HIF-1 alpha/15-LO/15-HETE pathway is therefore significantly associated within the pathology of PE.”
“Lipophilic marine toxins are produced by harmful microalgae and can accumulate in edible filter feeders such as shellfish, leading to an introduction of toxins into the human food chain, causing different poisoning effects. During the last years, analytical methods, based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), have been consolidated by interlaboratory validations.

\n\nMETHODS: We therefore analysed CD4 and CD8 T-cell responses

to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-gamma.\n\nRESULTS: Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly selleck chemical elevated serum AFP concentrations (P = 0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child-Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child-Pugh A score and in 46% with a B or C score.\n\nCONCLUSION: These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more

likely to be present in patients selleck screening library with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC. British Journal of Cancer (2010) 102, 748-753. doi:10.1038/sj.bjc.6605526 www.bjcancer.com Published online 19 January 2010 (C) 2010 Cancer Research UK”
“Although it is well known that 3,4-methylenedioxymethamphetamine see more (MDMA) can cause various cardiovascular abnormalities

and even sudden death from cardiac arrhythmia, whether it has any effect on myocardial gap junctions, which might be one of the targets mediating MDMA-induced cardiotoxicity, remains unclear.\n\nObjective: To test the hypothesis that MDMA may affect the myocardial gap junction protein connexin43 (Cx43) and induce cardiac dysrhythmia.\n\nMethod: (1) In vivo study: adult rats were treated with a single dose MDMA administration (20 mg/kg, i.p.). Electrocardiogram detection and immunohistochemical analysis were performed to evaluate cardiac function and expression of Cx43, respectively; (2) in vitro study: cultured ventricular myocytes of neonatal rats were treated with MDMA (10, 100, 1000 mu mol/L) for 1 h. Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to investigate the total Cx43 mRNA expression. Immunofluorescent analysis was used to evaluate the amount of junctional Cx43.

r.l. All rights reserved.”
“As a ligand-dependent transcription factor of the nuclear hormone receptor superfamily, the pregnane X receptor (PXR) has a multitude of functions including regulating xenobiotic and cholesterol metabolism, energy homeostasis, gut mucosal defense, and cancer development. Whereas the detoxification functions of PXR have been widely studied and well established, the role of PXR in cancer has become controversial. With more than 60% of non-prescription and prescription drugs being metabolized by cytochrome P450 enzyme 3A4 selleck screening library (CYP3A4), a transcriptional

target of PXR, insights into the regulation of PXR during systemic administration of novel treatment modalities will lead to a better understanding of PXR function in the context of human disease. Previous studies have

suggested that PXR activation decreases drug sensitivity and augments chemoresistance in certain colon cancers mainly through the upregulation of CYP3A4 and multidrug resistance protein-1 (MDR1). Later studies suggest that downregulation of PXR expression may be oncogenic in hormone-dependent breast and endometrial cancers by reducing estrogen metabolism via CYP3A4; thus, higher estradiol concentrations contribute to carcinogenesis. These results suggest a differential role of PXR in tumor growth P005091 regulation dependent on tissue type and tumor microenvironment. Here, we will summarize the various mechanisms utilized by PXR to induce its diverse effects on cancerous tissues. Moreover, current approaches will be explored to evaluate the exploitation of PXR-mediated pathways as a novel mechanistic approach to FK506 mw cancer therapy.”
“The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding

gene regulatory regions that they bind to, and the genes whose expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis and ChIP-seq, we identify several of the crucial TF regulators of NS cells. At the core of the network are TFs of the basic helix-loop-helix (bHLH), nuclear factor I (NFI), SOX, and FOX families, with CREs often densely bound by several of these different TFs. We use machine learning to highlight several crucial regulatory features of the network that underpin NS cell self-renewal and multipotency. We validate our predictions by functional analysis of the bHLH TF OLIG2. This TF makes an important contribution to NS cell self-renewal by concurrently activating pro-proliferation genes and preventing the untimely activation of genes promoting neuronal differentiation and stem cell quiescence.

91 nm tine arises mainly from the ionic tines of iron and copper in the steel. By choosing the gate delays carefully, the interference can be reduced. The spectral resolution and sensitivity of the spectrometer required for the detection of the P 1 214.91 nm line in steel

plasma were also studied. Based on the results, a Czerny-Turner spectrometer equipped with an intensified charge coupled device camera with Ruboxistaurin purchase a minimum spectral resolution of 0.03 nm is suggested for this application. Finally, the successful quantitative analysis of phosphorus in the UV-vis spectral range was carried out both in pig iron and a low alloy steel. For the pig iron, the R-2 calibration factor was 0.9992, the limit-of-detection (LoD) was 12 ppm and the background C59 chemical structure equivalent concentration (BEC)

was 0.11 wt%. For the low alloy steel, the R-2 calibration factor was 0.995, the LoD was 9 ppm and the BEC was 0.05 wt%. Interference from copper lines on the P I 214.91 nm line was not observed. It has been shown that a simple LIBS setup can be used for the accurate quantitative analysis of phosphorus in iron/low alloy steel in open air.”
“Insulin-like growth factor (IGF) signaling plays a pivotal role in cell proliferation and mitogenesis. Secreted IGF-binding proteins (IGFBPs) are important modulators of IGF bioavailability; however, their intracellular functions remain elusive. We sought to assess the antiapoptotic properties of intracellular IGFBP-2 in lung adenocarcinomas. IGFBP-2 overexpression resulted in a decrease in procaspase-3 expression; however, it did not influence the phosphorylation

status of either IGF receptor or its downstream targets, including Akt and extracellular signal-regulated kinase. Apoptosis induced by camptothecin check details was significantly inhibited by IGFBP-2 overexpression in NCI-H522 cells. Conversely, selective knockdown of IGFBP-2 using small-interfering RNA resulted in an increase in procaspase-3 expression and sensitization to camptothecin-induced apoptosis in NCI-H522 cells. LY294002, an inhibitor of phosphatidylinositol 3-kinase, caused a decrease in IGFBP-2 levels and enhanced apoptosis in combination with camptothecin. Immunohistochemistry demonstrated that intracellular IGFBP-2 was highly expressed in lung adenocarcinomas compared with normal epithelium. Intracellular IGFBP-2 and procaspase-3 were expressed in a mutually exclusive manner. These findings suggest that intracellular IGFBP-2 regulates caspase-3 expression and contributes to the inhibitory effect on apoptosis independent of IGF. IGFBP-2, therefore, may offer a novel therapeutic target and serve as an antiapoptotic biomarker for lung adenocarcinoma. (Am J. Pathol 2010, 176:1756-1766; DOI: 10.2353/ajpath.2010.

In particular, OCN was considerably elevated in primary MK-2206 HOB after 3 days on YZ-SE (13-fold) as well as YZ-SEH (12-fold) surfaces.

Shorter actin filaments without any favored orientation on YZ-SE and YZ-SEH surfaces are associated with higher roughness (R-a) values. Topographically modified yttria-stabilized zirconia is a likely material for dental implants with cell stimulating properties achieving or actually exceeding those of titanium.”
“Recent studies indicate that elasmobranch fish respond differently to metal exposure than marine teleosts. Accumulation rates can be high, which despite the fact that normal background levels for metals in the marine environment are low, is worrying due to the long life span and late fecundity of most shark. The goals of the present study were to examine differences in accumulation rates and toxicity of a range of metals at equimolar concentrations (10 mu M) in the Mediterranean or spotted dogfish, Scyliorhinus canicula. For this purpose, we exposed the dogfish buy GW-572016 to Ni (587 mu g/L), Cd (1124 mu g/L), Pb (2072 mu g/L), Cu (635 mu g/L), and Ag (1079 mu g/L and two additional exposures at 10 mu g/L and

1 mu g/L) for one week and measured total metal accumulation, metallothionein induction, and parameters related to osmoregulation. Our study confirms the high toxicity and accumulation rates of Ag for elasmobranch fish, even at levels 100 to 1000 times lower than exposure levels of other metals. Also Pb accumulated readily in all organs, but did not cause any osmoregulatory disturbance at the exposure levels used. Ni and Cd seem to accumulate primarily in the kidney while Cu mainly accumulated in liver. In contrast to Ni and Cd, the three other metals Ag, Cu and Pb accumulated in the rectal gland, an important organ for osmoregulation and possible target organ for metal toxicity. Only Cu succeeded in initiating a protective response by inducing MT synthesis in liver and gills. (c) 2010 Elsevier Inc. All rights reserved.”
“Seaweed

(Ulva sp.) stranded on beaches were utilized as co-substrate for anaerobic digestion of pig slurry in three-month co-digestion tests in pilot scale anaerobic KPT-8602 digesters in the laboratory. The methanogenic potential of Ulva sp. was low compared to that of other potential co-substrates available for use by farmers: 148 N m(3)CH(4)/t of volatile solids or 19 N m(3)CH(4)/t of crude product. When used as a co-substrate with pig manure (48%/52% w/w), Ulva sp. seaweed did not notably disrupt the process of digestion: however, after pilot stabilisation, biogas produced contained 3.5% H(2)S, making it unsuitable for energy recovery without treatment. Sequentially addition of the sulphate reduction inhibitor, potassium molybdate, to a final concentration of 3 mNil.

“
“Bayesian statistics provides a framework for the integration of dynamic models with incomplete data to enable inference of model parameters and unobserved aspects of the system under study. An important class of dynamic models is discrete state space, continuous-time Markov processes (DCTMPs). Simulated via the Doob-Gillespie algorithm, these have been used to model systems ranging from chemistry to ecology to epidemiology. A new type of proposal, termed ‘model-based proposal’

(MBP), is developed for the efficient implementation of Bayesian inference in DCTMPs using S3I-201 molecular weight Markov chain Monte Carlo (MCMC). This new method, which in principle can be applied to any DCTMP, is compared (using simple epidemiological SIS and SIR models as easy to follow exemplars) to a standard MCMC approach and a recently proposed particle MCMC (PMCMC) technique. When measurements are made on a single-state https://www.selleckchem.com/products/MS-275.html variable (e.g. the number of infected individuals in a population during an epidemic), model-based proposal MCMC (MBP-MCMC) is marginally faster than PMCMC (by a factor of 2-8 for the tests performed), and significantly faster than the standard MCMC scheme (by a factor of 400 at least). However, when model complexity increases and measurements are made

on more than one state variable (e.g. simultaneously on the number of infected individuals in spatially separated subpopulations), MBP-MCMC is significantly

faster than PMCMC (more than 100-fold for just four subpopulations) and this difference becomes increasingly large.”
“TNF alpha plays key roles in the regulation of inflammation, cell death, and proliferation and its signaling cascade cross-talks with the insulin signaling cascade. PKC delta, a novel PKC isoform, is known to participate in proximal TNF alpha signaling events. However, it has remained unclear whether PKC delta plays a role in distal TNF alpha signaling events. Here we demonstrate that PKCS is activated by TNF alpha in a delayed fashion that is temporally associated with JNK activation. To investigate the signaling pathways activating PKC delta and JNK we used pharmacological and genetic inhibitors of NF kappa B. We found that inhibition of NF kappa B attenuated https://www.selleckchem.com/products/emricasan-idn-6556-pf-03491390.html PKC delta and JNK activations. Further analysis revealed that ER stress contributes to TNF alpha-stimulated PKC delta and JNK activations. To investigate the role of PKC delta in TNF alpha action. we used 29-mer shRNAs to silence PKC delta expression. A reduction of similar to 90% in PKC delta protein levels reduced TNF alpha-stimulated stress kinase activation, including JNK. Further, PKC delta was necessary for thapsigargin-stimulated JNK activation. Because thapsigargin is a potent inducer of ER stress, we determined whether PKC delta was necessary for induction of the UPR.

In general, oxytocin had similar effects in both sexes. However, females were more

sensitive to lower doses of oxytocin than males. These findings are consistent with the notion that oxytocin regulates many of the same behaviors in males and females, but that the effects are typically more profound in females. Therapeutic use of oxytocin should include sex as a factor in determining dose regimens. (C) 2015 Elsevier B.V. All rights reserved.”
“An optimized approach to nonlinear iterative reconstruction of magnetic resonance imaging (MRI)-guided near-infrared spectral tomography (NIRST) images was developed using an L-curve-based algorithm for the choice of regularization parameter. This approach was applied to clinical exam data to maximize the reconstructed values differentiating malignant

Rabusertib solubility dmso and benign lesions. MRI/NIRST data from 25 patients with abnormal breast readings (BI-RADS category 4-5) were analyzed using this optimal regularization methodology, and the results showed enhanced p values and area under the curve (AUC) for the task of differentiating malignant from benign lesions. Of the four absorption parameters and two scatter parameters, the most significant differences for benign versus malignant were total hemoglobin (HbT) and tissue optical index (TOI) with p values = 0.01 and 0.001, and AUC values = 0.79 and 0.94, respectively, in terms of HbT and TOI. This dramatically improved the values relative to fixed regularization (p value = 0.02 and 0.003; AUC = 0.75 and 0.83) showing that more differentiation was possible with the optimal method. Through a combination Blasticidin S of both biomarkers, HbT and TOI, the AUC increased from 82.9% (fixed regulation = 0.1) to 94.3% (optimal method). (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)”
“The last decade has seen

dramatic advances in cardiac electrophysiology, particularly in its application for treatment of atrial fibrillation and other tachyarrhythmias. In this paper, the authors review key new technologies now beginning JNJ-26481585 mouse to impact on contemporary practice that are taking its therapeutic potential to new levels of efficacy and safety.”
“Background Uncontrolled studies comparing pentostatin (P), cyclophosphamide (C), and rituximab (R) (PCR) to fludarabine plus C+R (FCR) suggest similar efficacy with fewer infectious complications with PCR. We compared FCR and PCR in previously-untreated or minimally-treated B-cell chronic lymphocytic leukemia (CLL). Treatment FCR (F 20 mg/m(2) Days 1-5, C 600 mg/m(2) Day 1, R 375 mg/m(2) Day 1) (28-day cycles) or PCR (P 4 mg/m(2) Day 1, C 600 mg/m(2) Day 1, R 375 mg/m(2) Day 1) (21-day cycles). Dose 1 of R: 100 mg/m(2) was given on Day 8 Cycle 1 and the remainder on Day 9; in subsequent cycles the entire dose was given on Day 1. Results Ninety-two patients were randomly assigned to each group (N=184). Groups were balanced; similar to 20% had received prior chemotherapy.