bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triptolide sensitizes AML cells to TRAIL-induced apoptosis via decrease of XIAP and p53-mediated increase of DR5
Authors: Carter Bing Z. , Mak Duncan H. , Schober Wendy D. , Dietrich Martin F. , Pinilla Clemencia , Vassilev Lyubomir T. , Reed John C. , Andreeff Michael 
Published: January 2008

Abstract
Acute myeloid leukemia (AML) cells are relatively resistant to tumor necrosis factor α–related apoptosis-inducing ligand (TRAIL). We previously reported that triptolide, a potent anticancer agent from a Chinese herb, decreases XIAP in leukemic cells. We evaluated the combination of triptolide and TRAIL and found synergistic promotion of apoptosis in AML cells. XIAP-overexpressing U937 cells (U937XIAP) were more resistant to TRAIL than U937neo cells, and inhibition of XIAP with the small-molecule inhibitor 1396-11 enhanced TRAIL-induced apoptosis, implying XIAP as a resistance factor in AML. Furthermore, triptolide increased DR5 levels in OCI-AML3, while the DR5 increase was blunted in p53-knockdown OCI-AML3 and p53-mutated U937 cells, confirming a role for p53 in the regulation of DR5. In support of this finding, disruption of MDM2-p53 binding with subsequent increase in p53 levels by nutlin3a increased DR5 levels and sensitized OCI-AML3 cells to TRAIL. The combination of 1396-11 plus nutlin3a plus TRAIL was more effective than either the 1396-11 and TRAIL or nutlin3a and TRAIL combinations in OCI-AML3 cells, further supporting the role of triptolide as a sensitizer to TRAILinduced apoptosis in part by independent modulation of XIAP expression and p53 signaling. Thus, the combination of triptolide and TRAIL may provide a novel strategy for treating AML by overcoming critical mechanisms of apoptosis resistance.
Evidence-based diagnosis of type 1 von Willebrand disease: a Bayes theorem approach
Authors: Tosetto Alberto , Castaman Giancarlo , Rodeghiero Francesco 
Published: January 2008

AbstractThe diagnosis of type 1 von Willebrand disease (VWD) is based on the presence of bleeding symptoms, reduced von Willebrand factor (VWF) levels, and autosomal inheritance of the phenotype. To better appreciate the contribution of clinical and laboratory data to the final diagnosis of VWD, we computed the likelihoods of having VWD as a function of the bleeding score (LRscore), of VWF level (LRVWF), and of number of first-degree family members with reduced VWF levels (LRfamily). The 3 likelihoods were therefore combined using the Bayes theorem, giving the final probability (odds) of having VWD. LRfamily and LRVWF were the 2 factors mostly influencing the final probability of having VWD. Data from the present study provide an evidence-based description of the minimal criteria for the diagnosis of type 1 VWD. As an example, presence of VWF levels lower than 40 IU/dL in at least 2 family members (including the proband) and a bleeding score of at least 1 were found to be required for a final odd of VWD higher than 2.0 (false-positive rate less than one-half). Validation of this approach and of its clinical utility is, however, required by analysis in other cohorts of well-characterized type 1 VWD patients.
Recruitment of circulating NK cells through decidual tissues: a possible mechanism controlling NK cell accumulation in the uterus during early pregnancy
Authors: Carlino Claudia , Stabile Helena , Morrone Stefania , Bulla Roberta , Soriani Alessandra , Agostinis Chiara , Bossi Fleur , Mocci Carlo , Sarazani Filippo , Tedesco Francesco , Santoni Angela , Gismondi Angela 
Published: January 2008

AbstractDuring early pregnancy, uterine mucosa decidualization is accompanied by a drastic enrichment of CD56highCD16− natural killer (NK) cells. Decidual NK (dNK) cells differ from peripheral blood NK (pbNK) cells in several ways, but their origin is still unclear. Our results demonstrate that chemokines present in the uterus can support pbNK cell migration through human endothelial and stromal decidual cells. Notably, we observed that pregnant women's pbNK cells are endowed with higher migratory ability compared with nonpregnant women's or male donors' pbNK cells. Moreover, NK cell migration through decidual stromal cells was increased when progesterone-cultured stromal cells were used as substrate, and this correlated with the ability of progesterone to up-regulate stromal cell chemokine expression. Furthermore, we demonstrate that dNK cells migrate through stromal cells using a distinct pattern of chemokines. Finally, we found that pbNK cells acquire a chemokine receptor pattern similar to that of dNK cells when they contact decidual stromal cells. Collectively these results strongly suggest that pbNK cell recruitment to the uterus contributes to the accumulation of NK cells during early pregnancy; that progesterone plays a crucial role in this event; and that pbNK cells undergo reprogramming of their chemokine receptor profile once exposed to uterine microenvironment.
Halibut mitochondrial genomes contain extensive heteroplasmic tandem repeat arrays involved in DNA recombination
Authors: Mjelle Kenneth A , Karlsen Bård O , Jørgensen Tor E , Moum Truls , Johansen Steinar D 
Published: January 2008

Abstract

Background
Halibuts are commercially important flatfish species confined to the North Pacific and North Atlantic Oceans. We have determined the complete mitochondrial genome sequences of four specimens each of Atlantic halibut (Hippoglossus hippoglossus), Pacific halibut (Hippoglossus stenolepis) and Greenland halibut (Reinhardtius hippoglossoides), and assessed the nucleotide variability within and between species.

Results
About 100 variable positions were identified within the four specimens in each halibut species, with the control regions as the most variable parts of the genomes (10 times that of the mitochondrial ribosomal DNA). Due to tandem repeat arrays, the control regions have unusually large sizes compared to most vertebrate mtDNAs. The arrays are highly heteroplasmic in size and consist mainly of different variants of a 61-bp motif. Halibut mitochondrial genomes lacking arrays were also detected.

Conclusion
The complexity, distribution, and biological role of the heteroplasmic tandem repeat arrays in halibut mitochondrial control regions are discussed. We conclude that the most plausible explanation for array maintenance includes both the slipped-strand mispairing and DNA recombination mechanisms.
Profiling expression changes caused by a segmental aneuploid in maize
Authors: Makarevitch Irina , Phillips Ronald L , Springer Nathan M 
Published: January 2008

Abstract

Background
While changes in chromosome number that result in aneuploidy are associated with phenotypic consequences such as Down syndrome and cancer, the molecular causes of specific phenotypes and genome-wide expression changes that occur in aneuploids are still being elucidated.

Results
We employed a segmental aneuploid condition in maize to study phenotypic and gene expression changes associated with aneuploidy. Maize plants that are trisomic for 90% of the short arm of chromosome 5 and monosomic for a small distal portion of the short arm of chromosome 6 exhibited a phenotypic syndrome that includes reduced stature, tassel morphology changes and the presence of knots on the leaves. The knotted-like homeobox gene knox10, which is located on the short arm of chromosome 5, was shown to be ectopically expressed in developing leaves of the aneuploid plants. Expression profiling revealed that ~40% of the expressed genes in the trisomic region exhibited the expected 1.5 fold increased transcript levels while the remaining 60% of genes did not show altered expression even with increased gene dosage.

Conclusion
We found that the majority of genes with altered expression levels were located within the chromosomal regions affected by the segmental aneuploidy and exhibits dosage-dependent expression changes. A small number of genes exhibit higher levels of expression change not predicted by the dosage, or display altered expression even though they are not located in the aneuploid regions.
Clinical presentation and outcome of Tuberculosis in Human Immunodeficiency Virus infected children on anti-retroviral therapy
Authors: Walters Elisabetta , Cotton Mark F , Rabie Helena , Schaaf H Simon , Walters Lourens O , Marais Ben J 
Published: January 2008

Abstract

Background
The tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics are poorly controlled in sub-Saharan Africa, where highly active antiretroviral treatment (HAART) has become more freely available. Little is known about the clinical presentation and outcome of TB in HIV-infected children on HAART.

Methods
We performed a comprehensive file review of all children who commenced HAART at Tygerberg Children's Hospital from January 2003 through December 2005.

Results
Data from 290 children were analyzed; 137 TB episodes were recorded in 136 children; 116 episodes occurred before and 21 after HAART initiation; 10 episodes were probably related to immune reconstitution inflammatory syndrome (IRIS). The number of TB cases per 100 patient years were 53.3 during the 9 months prior to HAART initiation, and 6.4 during post HAART follow-up [odds ratio (OR) 16.6; 95% confidence interval (CI) 12.5–22.4]. A positive outcome was achieved in 97/137 (71%) episodes, 6 (4%) cases experienced no improvement, 16 (12%) died and the outcome could not be established in 18 (13%). Mortality was less in children on HAART (1/21; 4.8%) compared to those not on HAART (15/116; 12.9%).

Conclusion
We recorded an extremely high incidence of TB among HIV-infected children, especially prior to HAART initiation. Starting HAART at an earlier stage is likely to reduce morbidity and mortality related to TB, particularly in TB-endemic areas. Management frequently deviated from standard guidelines, but outcomes in general were good.
Preclinical evaluation of lime juice as a topical microbicide candidate
Authors: Fletcher Patricia S , Harman Sarah J , Boothe Adrienne R , Doncel Gustavo F , Shattock Robin J 
Published: January 2008

Abstract

Background
The continued growth of the global HIV epidemic highlights the urgent need to develop novel prevention strategies to reduce HIV transmission. The development of topical microbicides is likely to take a number of years before such a product would be widely available. This has resulted in a call for the rapid introduction of simpler vaginal intervention strategies in the interim period. One suggested practice would be vaginal douching with natural products including lime or lemon juice. Here we present a comprehensive preclinical evaluation of lime juice (LiJ) as a potential intervention strategy against HIV.

Results
Pre-treatment of HIV with LiJ demonstrated direct virucidal activity, with 10% juice inactivating the virus within 5 minutes. However, this activity was significantly reduced in the presence of seminal plasma, where inactivation required maintaining a 1:1 mixture of neat LiJ and seminal plasma for more than 5 minutes. Additionally, LiJ demonstrated both time and dose-dependent toxicity towards cervicovaginal epithelium, where exposure to 50% juice caused 75–90% toxicity within 5 minutes increasing to 95% by 30 minutes. Cervicovaginal epithelial cell monolayers were more susceptible to the effects of LiJ with 8.8% juice causing 50% toxicity after 5 minutes. Reconstructed stratified cervicovaginal epithelium appeared more resilient to LiJ toxicity with 30 minutes exposure to 50% LiJ having little effect on viability. However viability was reduced by 75% and 90% following 60 and 120 minutes exposure. Furthermore, repeat application (several times daily) of 25% LiJ caused 80–90% reduction in viability.

Conclusion
These data demonstrate that the virucidal activity of LiJ is severely compromised in the presence of seminal plasma. Potentially, to be effective against HIV in vivo, women would need to apply a volume of neat LiJ equal to that of an ejaculate, and maintain this ratio vaginally for 5–30 minutes after ejaculation. Data presented here suggest that this would have significant adverse effects on the genital mucosa. These data raise serious questions about the plausibility and safety of such a prevention approach.
Effect of shoe heel height on vastus medialis and vastus lateralis electromyographic activity during sit to stand
Authors: Edwards Lindsay , Dixon John , Kent Jillian R , Hodgson David , Whittaker Vicki J 
Published: January 2008

Abstract

Background
It has been proposed that high-heeled shoes may contribute to the development and progression of knee pain. However, surprisingly little research has been carried out on how shoe heel height affects muscle activity around the knee joint. The purpose of this study was to investigate the effect of differing heel height on the electromyographic (EMG) activity in vastus medialis (VM) and vastus lateralis (VL) during a sit to stand activity. This was an exploratory study to inform future research.

Methods
A repeated measures design was used. Twenty five healthy females carried out a standardised sit to stand activity under 4 conditions; barefoot, and with heel wedges of 1, 3, and 5 cm in height. EMG activity was recorded from VM and VL during the activity. Data were analysed using 1 × 4 repeated measures ANOVA.

Results
Average rectified EMG activity differed with heel height in both VM (F2.2, 51.7 = 5.24, p < 0.01), and VL (F3, 72 = 5.32, p < 0.01). However the VM: VL EMG ratio was not significantly different between conditions (F3, 72 = 0.61, p = 0.609).

Conclusion
We found that as heel height increased, there was an increase in EMG activity in both VM and VL, but no change in the relative EMG intensity of VM and VL as measured by the VM: VL ratio. This showed that no VM: VL imbalance was elicited. This study provides information that will inform future research on how heel height affects muscle activity around the knee joint.
Extracellular calcium increases bisphosphonate-induced growth inhibition of breast cancer cells
Authors: Journé Fabrice , Kheddoumi Naïma , Chaboteaux Carole , Duvillier Hugues , Laurent Guy , Body Jean-Jacques 
Published: January 2008

Abstract
Introduction
Bisphosphonates have become standard therapy for the treatment of skeletal complications related to breast cancer. Although their therapeutic effects mainly result from an inhibition of osteoclastic bone resorption, in vitro data indicate that they also act directly on breast cancer cells, inhibiting proliferation and inducing apoptosis.

Methods
The present study examined the effects of calcium (from 0.6 to 2.0 mmol/l) on the antitumour activity of the bisphosphonate ibandronate (1 to 1,000 nmol/l) on MDA-MB-231 and MCF-7 breast cancer cells. Cell culture densities were determined using crystal violet staining assay. Apoptotic cell death was assessed by annexin V-phycoerythrin and 7-amino-actinomycin double staining.

Results
At low calcium concentration, 30 μmol/l ibandronate had no effect on MDA-MB-231 cells growth and only slightly inhibited MCF-7 cells growth. Higher calcium levels significantly increased growth inhibition as well as cell apoptosis induced by ibandronate. We observed similar effects with zoledronic acid. Of note, enhancement of ibandronate-induced growth inhibition was also observed in other breast cancer cell lines (T-47D, ZR-75, Hs-578T and BT-549 cells). The growth inhibitory effect of ibandronate in the presence of high concentrations of calcium was partly suppressed by the calcium chelator EGTA (ethylene glycol tetra-acetic acid). In addition, in the presence of calcium at high concentrations, cells accumulated more [14C]ibandronate than at low calcium concentrations. We obtained further evidence of enhancement of cellular ibandronate accumulation by calcium by demonstrating that high calcium levels increased the inhibition of protein prenylation induced by the bisphosphonate.

Conclusion
Altogether, our data suggest that extracellular calcium, probably through its binding to ibandronate, markedly increased its cellular accumulation and its inhibitory activity on breast tumour cells. Thus, calcium released during the process of tumour-induced osteolysis might enhance the antitumour effects of bisphosphonates and contribute to their therapeutic efficacy.
Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions
Authors: Bruegger Dirk , Kemming Gregor I , Jacob Matthias , Meisner Franz G , Wojtczyk Christoph J , Packert Kristian B , Keipert Peter E , Faithfull N Simon , Habler Oliver P , Becker Bernhard F , Rehm Markus 
Published: January 2008

Abstract
Introduction
Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis.

Methods
Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured at baseline, in shock, and during 3 hours post-therapy. Strong ion difference and the amount of weak plasma acid were calculated. To detect the presence of unmeasured anions, anion gap and strong ion gap were determined. Capillary electrophoresis was used to identify potential contributors to unmeasured anions.

Results
During induction of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to explain the transient increases in anion gap (+11.0 mEq/L) and strong ion gap (+7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have been generated. Capillary electrophoresis revealed increases in serum concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), α-ketoglutarate (35.3 μEq/L), fumarate (6.2 μEq/L), sulfate (0.1 mEq/L), and urate (55.9 μEq/L) after shock induction.

Conclusion
Large amounts of unmeasured anions were generated after hemorrhage in this highly standardized model of hemorrhagic shock. Capillary electrophoresis suggested that the hitherto unmeasured anions citrate and acetate, but not sulfate, contributed significantly to the changes in strong ion gap associated with induction of shock.
Housestaff Activism: The Emergence of Patient-Care Demands
Authors: Hoffman Lily M. 
Published: January 2008

There have been two trends within the physician housestaff movement: increased acceptance of collective bargaining and unions, and a shift from narrower economic to broader political demands, including some involving patient care. Case studies of politically active housestaff associations in New York, Chicago, and Los Angeles are used to examine the emergence of “patient-care” demands and their compatibility with collective bargaining frameworks. As house-staff have become principal providers of care to indigent populations in public hospitals, and economic cutbacks have endangered service as well as the positions of physicians, patient-care demands arise and become infused with demands for participation and control in decision-making. Common factors in the politicization of housestaff have been the contribution of activists of the sixties as leaders, and the impact of fiscal crisis and economic retrenchment in the seventies.
However, the emergence and resolution of these issues has differed, depending upon legal, political, historical, and organizational variations. In general, patient-care issues are supported by housestaff when they dovetail with housestaff interests. However, physician interests can diverge from those of patients, as in the case of manpower redistribution. On the whole, wages and benefits have done better than educational or patient-care demands. Educational demands have met with counterattack, and patient care, limited by the traditional scope of collective bargaining, has had to evolve indirectly, and has been hurt by long-term economic trends. Finally, national housestaff organization is limited by the wide-ranging politics and ideas of diverse regional organizations which represent different types of training institutions and career orientations.
Extractive Spectrophotometric Determination of Tungsten(VI) as Its 6-Chloro-3-hydroxy-2-(2′-thienyl)-4-oxo-4H-1-benzopyran Complex
Authors: Agnihotri Rajesh , Agnihotri Nivedita , Mehta Jaswant Ram 
Published: January 2008

Abstract
An extractive spectrophotometric method was developed for the trace determination of tungsten in an acidic medium. A yellow-colored 1:3 complex of tungsten(VI) and 6-chloro-3-hydroxy-2-(2′-thienyl)-4-oxo-4H-1-benzopyran (CHTB), prepared in 0.16–0.32 mol dm−3 hydrochloric acid medium, was quantitatively extracted into chloroform. The complex had a maximum absorbance at 417–423 nm. The method obeyed Beer’s law in the range of 0–3.0 μg cm−3 WVI; the correlation coefficient was r=0.9902. The molar absorptivity and Sandell’s sensitivity of the complex were 4.05×104 dm3 mol−1 cm−1 and 0.0045 μg of WVI cm−2, respectively, at 420 nm. Various metals, including Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Nb, Ta, Mo, U, Zr, Th, Ce, Re, and various platinum metals did not interfere in the extraction, and this procedure was satisfactorily applied to the analysis of tungsten in various synthetic, technical and natural samples, including reverberatory flue dust and water.
Beyond switches: Rotaxane- and catenane-based synthetic molecular motors
Authors: Kay Euan R. , Leigh David A. 
Published: January 2008

AbstractNature uses molecular motors and machines in virtually every significant biological process, but learning how to design and assemble simpler artificial structures that function through controlled molecular-level motion is a major challenge for contemporary physical science. The established engineering principles of the macroscopic world can offer little more than inspiration to the molecular engineer who creates devices for an environment where everything is constantly moving and being buffeted by other atoms and molecules. Rather, experimental designs for working molecular machines must follow principles derived from chemical kinetics, thermodynamics, and nonequilibrium statistical physics. The remarkable characteristics of interlocked molecules make them particularly useful for investigating the control of motion at the molecular level. Yet, the vast majority of synthetic molecular machines studied to date are simple two-state switches. Here we outline recent developments from our laboratory that demonstrate more complex molecular machine functions. This new generation of synthetic molecular machines can move continuously and progressively away from equilibrium, and they may be considered true prototypical molecular motors. The examples discussed exemplify two, fundamentally different, "Brownian ratchet" mechanisms previously developed in theoretical statistical physics and realized experimentally in molecular-level devices for the first time in these systems.