bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical Identification of Ideal Pulmonary-Systemic Flow Balance in Patients With Bidirectional Cavopulmonary Shunt and Univentricular Circulation
Authors: Diller Gerhard-Paul , Uebing Anselm , Willson Keith , Davies L. Ceri , Dimopoulos Konstantinos , Thorne Sara A. , Gatzoulis Michael A. , Francis Darrel P.
Published: September 2006

Background—

In the present study, we extended previous mathematical modeling work on patients with bidirectional cavopulmonary (“bidirectional Glenn”) anastomosis to assess the potential utility of several descriptors of oxygen status. We set out to determine which of these descriptors best represents the overall tissue oxygenation. We also introduce a new descriptor, S
o
2
min, defined as the lower of the superior and inferior vena cava oxygen saturations.

Methods and Results—

The application of differential calculus to a model of oxygen physiology of patients with bidirectional Glenn allowed simultaneous assessment of all possible distributions of blood flow and metabolic rate between upper and lower body, across all cardiac outputs, total metabolic rates, and oxygen-carrying capacities. When total cardiac output is fixed, although it may intuitively seem best to distribute flow to maximize oxygen delivery (total, upper body, or lower body), we found that for each variable, there are situations in which its maximization seriously deprives flow to the upper or lower circulation. In contrast, maximizing S
o
2
min always gives physiologically sensible results. If the majority of metabolism is in the upper body (typical of infancy), then oxygenation is optimized when flow distribution matches metabolic distribution. In contrast, if the majority of metabolism is in the lower body (typical of older children and during exercise), oxygenation is optimal when flows are equal.

Conclusions—

In patients with bidirectional cavopulmonary anastomosis, because there is a tradeoff between flow distribution and saturation, it is unwise to concentrate on maximizing oxygen delivery. Maximizing systemic venous saturations (especially S
o
2
min) is conceptually different and physiologically preferable for tissue oxygenation.
Nitrative Inactivation of Thioredoxin-1 and Its Role in Postischemic Myocardial Apoptosis
Authors: Tao Ling , Jiao Xiangying , Gao Erhe , Lau Wayne B. , Yuan Yuexing , Lopez Bernard , Christopher Theodore , RamachandraRao Satish P. , Williams William , Southan Garry , Sharma Kumar , Koch Walter , Ma Xin L.
Published: September 2006

Background—

Intracellular proteins involved in oxidative stress and apoptosis are nitrated in diseased tissues but not in normal tissues; definitive evidence to support a causative link between a specific protein that is nitratively modified with tissue injury in a specific disease is limited, however. The aims of the present study were to determine whether thioredoxin (Trx), a novel antioxidant and antiapoptotic molecule, is susceptible to nitrative inactivation and to establish a causative link between Trx nitration and postischemic myocardial apoptosis.

Methods and Results—

In vitro exposure of human Trx-1 to 3-morpholinosydnonimine resulted in significant Trx-1 nitration and almost abolished Trx-1 activity. 3-morpholinosydnonimine–induced nitrative Trx-1 inactivation was completely blocked by MnTE-2-PyP
5+
(a superoxide dismutase mimetic) and markedly attenuated by PTIO (a nitric oxide scavenger). Administration of either reduced or oxidized Trx-1 in vivo attenuated myocardial ischemia/reperfusion injury (>50% reduction in apoptosis and infarct size,
P
<0.01). However, administration of nitrated Trx-1 failed to exert a cardioprotective effect. In cardiac tissues obtained from ischemic/reperfused heart, significant Trx-1 nitration was detected, Trx activity was markedly inhibited, Trx-1/ASK1 (apoptosis signal-regulating kinase-1) complex formation was abolished, and apoptosis signal-regulating kinase-1 activity was increased. Treatment with either FP15 (a peroxynitrite decomposition catalyst) or MnTE-2-PyP
5+
10 minutes before reperfusion blocked nitrative Trx inactivation, attenuated apoptosis signal-regulating kinase-1 activation, and reduced postischemic myocardial apoptosis.

Conclusions—

These results strongly suggest that nitrative inactivation of Trx plays a proapoptotic role under those pathological conditions in which production of reactive nitrogen species is increased and that antinitrating treatment may have therapeutic value in those diseases, such as myocardial ischemia/reperfusion, in which pathological apoptosis is increased.
Static Dipole Polarizability and Hyperpolarizability of F2 from Density Functional Theory Calculations. Similarities and Dissimilarities with Conventional ab initio Results
Authors: Maroulis George , Makris Constantine
Published: September 2006

We have calculated the bond-length dependence of the static dipole polarizability and hyperpolarizability of F2 relying on finite-field density functional calculations. At the internuclear separation of Re = 2.66816 a0 we obtain α/ e2a0 2Eh-1 = 8.73 (B3LYP) and 8.60 (B3PW91),α./ e2a0 2Eh-1 = 6.42 (B3LYP) and 6.32 (B3PW91), γ / e4a04Eh-3 = 535 (B3LYP) and 503 (B3PW91) with a large, flexible [9s6p4d1f] basis set. For all three properties we observe that both B3LYPand B3PW91 yield values above the more accurate CCSD(T) results: CCSD(T) < B3PW91 < B3LYP. The discrepancy between DFT and conventional ab initio methods is more pronounced for the anisotropy of the (hyper)polarizability.
An Elegant l-exclusion Algorithm for Shared Memory Systems
Authors: Aravind Alex A.
Published: September 2006

Recent advancement of embedded systems and growing popularity of Java renew the interest to some classic process coordination problems, such as mutual exclusion problem and its generalization called l-exclusion problem. These are fundamental problems in parallel and distributed processing systems. The l-exclusion problem was introduced by Fischer et al.[9] for shared memory systems and subsequently studied in [6, 10, 2, 3, 4, 12, 1, 11]. In this paper, we present a simple solution to l-exclusion problem and prove its correctness. Our solution is efficient both in time and space.
Group Cohesion and Social Support in Exercise Classes: Results From a Danish Intervention Study
Authors: Christensen Ulla , Schmidt Lone , Budtz-Jørgensen Esben , Avlund Kirsten
Published: September 2006

This study examines the formation of group cohesion and social support in exercise classes among former sedentary adults, participating in a Danish community-based intervention. Furthermore, the aim is to analyze the impact of this process on exercise activity among the participants. A multimethod approach was used, analyzingboth survey data and 18 personalinterviews collected among87 participantswho completedthe intervention project. Analysis was performed according to the grounded theory method. The formation of group cohesion was conditioned by the social composition of the group, the teaching ability by the instructors, and the activity by itself. The cohesive group was characterized by an attitude of mutual support toward exercise activities. This mutual support facilitated development of self-efficacy beliefs among the participants improving their mastery expectation regarding exercise. Manipulating group dynamics may be a promising intervention tool in the promotion of leisure-time physical activity.
Effects of an Art-Based Curriculum on Clinical Trials Attitudes and Breast Cancer Prevention Knowledge
Authors: Herman Patricia M. , Larkey Linda K.
Published: September 2006

Although Latinos now comprise the largest minority in the U.S. population, they continue to be seriously underrepresented in clinical trials. A nonrandomized controlled study of an innovative community-developed clinical trial and breast cancer education program targeting Latinas tested whether use of an art-based curriculum could increase willingness to enroll in six clinical trial scenarios and increase breast health and clinical trial knowledge. The art-based curriculum resulted in a larger increase in stated willingness to enroll across all clinical trial scenarios, and the difference was statistically significant ( p < .05) in three. Breast health and clinical trials knowledge increased similarly and significantly for both groups. The results of this study show promise for the use of a community-developed art-based curriculum in the Latina population to increase willingness to enroll in clinical trials.
Effect of a Ban on Extracurricular Sports Activities by Secondary School Teachers on Physical Activity Levels of Adolescents: A Multilevel Analysis
Authors: Pabayo Roman , O'Loughlin Jennifer , Gauvin Lise , Paradis Gilles , Gray-Donald Katherine
Published: September 2006

To study the effect of a teachers' ban on supervising sports-related extracurricular physical activities (ECAs), levels of physical activity among 979 grade 7 students (mean age = 12.7 [0.5] years at baseline) were comparedduringand after the ban in seven schools that fully implementedthe ban, and three schools that did not implement the ban fully. On average, schools offered 18.0 ( SD = 5.1) ECAs during a no-ban school year. Students attending full implementation schools were significantly more likely than students in nonimplementation schoolsto be active after the banended(oddsratio forbeingactive = 1.89[95%confidenceinterval: 1.39,2.58]). They also increased the number of physical activities in which they participated (coefficient = 4.04; SE = 1.01). Ending a teachers' ban on sports-related ECAs was associated with increased involvement in physical activity among secondary school students.
Retention in a Breast Cancer Risk Information Trial: Motivations of a Population-Based Sample of Women
Authors: Ariail Kiley , Watts Carolyn (Cindy) , Bowen Deborah J.
Published: September 2006

A better understanding of factors influencing retention in breast cancer risk education and prevention programs can improve the design and effectiveness of such programs. Such information may also be useful to researchers seeking to maximize full retention in research trials involving low risk and low perceived benefit by the participants. These data are from a population-based study of 481 women from the Seattle, Washington, area, with diverse levels of breast cancer risk. This study sought to describe motivations for retention, to relate motivation variables to demographic characteristics, and to evaluate predictors of retention. Increasing age predicted study assessment completion, and both cancer worry and White ethnicity predicted intervention retention.
Perspective: The Community Barometer: A Breast Health Needs Assessment Tool for Community-Based Organizations
Authors: Lounsbury David , Rapkin Bruce , Marini Lisa , Jansky Elizabeth , Massie Mary Jane
Published: September 2006

This article presents findings from the ACCESS Project focusing on the impact of an outreach initiative that used “data sharing” as a mechanism to establish a wide variety of academic–community partnerships for cancer awareness. The Community Barometer, a brief needs assessment tool developed for this purpose, was used to collect data from clients, and sometimes staff members, of a variety of community-based organizations in New York City. Over a 5-year period, Barometer data were collected from 1,001 women who were affiliated with 20 community-based organizations. Analysis of these data supported our hypothesis that community-based organizations are more likely than chance to serve women with similar needs and preferences for breast health education and screening and that customized or tailored programs were warranted. Four case studies are presented. Limitations of the instrument and its administration in community settings as well as future research objectives are discussed.
Breast Self-Examination Among Chinese Immigrant Women
Authors: Wong-Kim Evaon , Wang Caroline C.
Published: September 2006

The incidence of breast cancer is rising rapidly among the fast-growing demographic group of Asian American and Pacific Islanders (AAPIs). In this study, the authors assessed the awareness of breast self-exam (BSE) and factors predicting practice of BSE among Chinese immigrant women living in San Francisco. Three hundred and ninety-seven women participated in a telephone survey; 80.9% reported having heard of BSE but only 53.9% reported practice of BSE during the past year. Logistic regression modeling found that increased length of stay in the United States, higher income, socializing with more Chinese than non-Chinese, and a birthplace other than U.S. and Chinese communities predicted BSE practice. The findings indicate that although familiarity with BSE is high among this group of Chinese immigrant women, self-reported actual practice is far from optimal. This study points to the need for culturally appropriate interventions that will encourage and motivate immigrant Chinese women to practice BSE on a monthly basis.
Does WoW Change Everything?
Authors: Taylor T. L.
Published: September 2006

Rather than simply identifying “emergence” as a prime property of massively multiplayer online game life, a better understanding of the complex nature of player-produced culture is needed. Life in game worlds is not exempt from forms of player-based regulation and control. Drawing on ethnographic and interview work within World of Warcraft, the author undertakes initial inquiries on this subject by looking at three areas: nationalism, age, and surveillance. This case study shows systems of stratification and control can arise from the bottom up and be implemented in not only everyday play culture but even player-produced modifications to the game system itself. Due to the ways these systems may simultaneously facilitate play, there is often an ambivalent dynamic at work. This piece also prompts some methodological considerations. By discussing field site choice, the author argues that context is of utmost importance and needs to be more thoughtfully foregrounded within game studies.
Blood Scythes, Festivals, Quests, and Backstories
Authors: Krzywinska Tanya
Published: September 2006

One of the pleasures of playing in the “World” of Warcraft is becoming part of its pervasive mythology. This article argues that to understand the game’s formal, aesthetic, and structural specificity, its pleasures and potential meanings, it is essential to investigate how the mythic functions. The author shows that the mythic plays a primary role in making a consistent fantasy world in terms of game play, morality, culture, time, and environment. It provides a rationale for players’ actions, as well as the logic that under- pins the stylistic profile of the game, its objects, tasks, and characters. In terms of the “cultural” environments of the game, the presence of a coherent and extensive myth scheme is core to the way differences and conflicts between races are organized. And, as a form of intertextual resonance, its mythology furnishes the game with a “thickness” of meaning that promotes, for players, a sense of mythological being as well as encouraging an in-depth textual engagement.
WoW is the New MUD
Authors: Mortensen Torill Elvira
Published: September 2006

With the immense popularity of massively multiplayer games such as World of Warcraft (WoW), other media as well as game research have discovered gaming as a topic of discussion and study. These discussions, however, tend to ignore the history of both games and of game studies. This article addresses the connections between one of the old and, today, obscure forms of using computers for multiplayer gaming—the text-based Multi-User Dungeon (MUD)—and the current, highly visible and massively used graphic interface game World of Warcraft. These connections range from player style through game-play options to social interaction and player-controlled social modifiers within both types of games. The comparison is based on play, observation, and interviews with players in MUDs and in WoW.
Endogenous laminin is required for human airway smooth muscle cell maturation
Authors: Tran Thai , McNeill Karol D , Gerthoffer William T , Unruh Helmut , Halayko Andrew J
Published: September 2006

Background

Airway smooth muscle (ASM) contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM) components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells.

Methods

Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured.

Results

Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP) significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype.

Conclusion

While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the first time that endogenously expressed laminin is required for ASM maturation to the contractile phenotype. As endogenously expressed laminin chains α2, β1 and γ1 are uniquely increased during myocyte maturation, these laminin chains may be key in this process. Thus, human ASM maturation appears to involve regulated endogenous expression of a select set of laminin chains that are essential for accumulation of contractile phenotype myocytes.
PET-Tool: a software suite for comprehensive processing and managing of Paired-End diTag (PET) sequence data
Authors: Chiu Kuo Ping , Wong Chee-Hong , Chen Qiongyu , Ariyaratne Pramila , Ooi Hong Sain , Wei Chia-Lin , Sung Wing-Kin Ken , Ruan Yijun
Published: September 2006

Background

We recently developed the Paired End diTag (PET) strategy for efficient characterization of mammalian transcriptomes and genomes. The paired end nature of short PET sequences derived from long DNA fragments raised a new set of bioinformatics challenges, including how to extract PETs from raw sequence reads, and correctly yet efficiently map PETs to reference genome sequences. To accommodate and streamline data analysis of the large volume PET sequences generated from each PET experiment, an automated PET data process pipeline is desirable.

Results

We designed an integrated computation program package, PET-Tool, to automatically process PET sequences and map them to the genome sequences. The Tool was implemented as a web-based application composed of four modules: the Extractor module for PET extraction; the Examiner module for analytic evaluation of PET sequence quality; the Mapper module for locating PET sequences in the genome sequences; and the ProjectManager module for data organization. The performance of PET-Tool was evaluated through the analyses of 2.7 million PET sequences. It was demonstrated that PET-Tool is accurate and efficient in extracting PET sequences and removing artifacts from large volume dataset. Using optimized mapping criteria, over 70% of quality PET sequences were mapped specifically to the genome sequences. With a 2.4 GHz LINUX machine, it takes approximately six hours to process one million PETs from extraction to mapping.

Conclusion

The speed, accuracy, and comprehensiveness have proved that PET-Tool is an important and useful component in PET experiments, and can be extended to accommodate other related analyses of paired-end sequences. The Tool also provides user-friendly functions for data quality check and system for multi-layer data management.
A biological question and a balanced (orthogonal) design: the ingredients to efficiently analyze two-color microarrays with Confirmatory Factor Analysis
Authors: Crijns Anne PG , Gerbens Frans , Plantinga A Edo D , Meersma Gert Jan , de Jong Steven , Hofstra Robert MW , de Vries Elisabeth GE , van der Zee Ate GJ , de Bock Geertruida H , te Meerman Gerard J
Published: September 2006

Background

Factor analysis (FA) has been widely applied in microarray studies as a data-reduction-tool without any a-priori assumption regarding associations between observed data and latent structure (Exploratory Factor Analysis).

A disadvantage is that the representation of data in a reduced set of dimensions can be difficult to interpret, as biological contrasts do not necessarily coincide with single dimensions. However, FA can also be applied as an instrument to confirm what is expected on the basis of pre-established hypotheses (Confirmatory Factor Analysis, CFA). We show that with a hypothesis incorporated in a balanced (orthogonal) design, including 'SelfSelf' hybridizations, dye swaps and independent replications, FA can be used to identify the latent factors underlying the correlation structure among the observed two-color microarray data. An orthogonal design will reflect the principal components associated with each experimental factor. We applied CFA to a microarray study performed to investigate cisplatin resistance in four ovarian cancer cell lines, which only differ in their degree of cisplatin resistance.

Results

Two latent factors, coinciding with principal components, representing the differences in cisplatin resistance between the four ovarian cancer cell lines were easily identified. From these two factors 315 genes associated with cisplatin resistance were selected, 199 genes from the first factor (False Discovery Rate (FDR): 19%) and 152 (FDR: 24%) from the second factor, while both gene sets shared 36. The differential expression of 16 genes was validated with reverse transcription-polymerase chain reaction.

Conclusion

Our results show that FA is an efficient method to analyze two-color microarray data provided that there is a pre-defined hypothesis reflected in an orthogonal design.
Hypoxia induces telomerase reverse transcriptase (TERT) gene expression in non-tumor fish tissues in vivo: the marine medaka (Oryzias melastigma) model
Authors: Yu Richard MK , Chen Eric XH , Kong Richard YC , Ng Patrick KS , Mok Helen OL , Au Doris WT
Published: September 2006

Background

Current understanding on the relationships between hypoxia, hypoxia-inducible factor-1 (HIF-1) and telomerase reverse transcriptase (TERT) gene expression are largely based on in vitro studies in human cancer cells. Although several reports demonstrated HIF-1- mediated upregulation of the human TERT gene under hypoxia, conflicting findings have also been reported. Thus far, it remains uncertain whether these findings can be directly extrapolated to non-tumor tissues in other whole animal systems in vivo. While fish often encounter environmental hypoxia, the in vivo regulation of TERT by hypoxia in non-neoplastic tissues of fish remains virtually unknown.

Results

The adult marine medaka (Oryzias melastigma) was employed as a model fish in this study. We have cloned and characterized a 3261-bp full-length TERT cDNA, omTERT, which encodes a protein of 1086 amino acids. It contains all of the functional motifs that are conserved in other vertebrate TERTs. Motif E is the most highly conserved showing 90.9–100% overall identity among the fish TERTs and 63.6% overall identity among vertebrates. Analysis of the 5'-flanking sequence of the omTERT gene identified two HRE (hypoxia-responsive element; nt. – 283 and – 892) cores. Overexpression of the HIF-1α induced omTERT promoter activity as demonstrated using transient transfection assays. The omTERT gene is ubiquitously expressed in fish under normoxia, albeit at varying levels, where highest expression was observed in gonads and the lowest in liver. In vivo expression of omTERT was significantly upregulated in testis and liver in response to hypoxia (at 96 h and 48 h, respectively), where concomitant induction of the omHIF-1α and erythropoietin (omEpo) genes was also observed. In situ hybridization analysis showed that hypoxic induction of omTERT mRNA was clearly evident in hepatocytes in the caudal region of liver and in spermatogonia-containing cysts in testis.

Conclusion

This study demonstrates for the first time, hypoxic regulation of TERT expression in vivo in a whole fish system. Our findings support the notion that hypoxia upregulates omTERT expression via omHIF-1 in non-neoplastic fish liver and testis in vivo. Overall, the structure and regulation of the TERT gene is highly conserved in vertebrates from fish to human.
The effect of socioeconomic status on three-year mortality after first-ever ischemic stroke in Nanjing, China
Authors: Zhou Guangyi , Liu Xinfeng , Xu Gelin , Liu Xifei , Zhang Renliang , Zhu Wusheng
Published: September 2006

Background

Low socioeconomic status (SES) is associated with increased mortality after stroke in developed countries. This study was performed to determine whether a similar association also exists in China.

Methods

A total of 806 patients with first-ever ischemic stroke were enrolled in our study. From August 1999 to August 2005, the three-year all-cause mortality following the stroke was determined. Level of education, occupation, taxable income and housing space were used as indicators for SES. Stepwise univariate and multivariate COX proportional hazards models were used to study the association between the SES measures and the three-year mortality.

Results

Our analyses confirmed that occupation, taxable income and housing space were significantly associated with three-year mortality after first-ever stroke. Manual workers had a significant hazard ratio of 5.44 (95% CI 2.75 to 10.77) for death within three years when compared with non-manual workers. Those in the zero income group had a significant hazard ratio of 5.35 (95% CI 2.95 to 9.70) and those in the intermediate income group 2.10 (95% CI 1.24 to 3.58) when compared with those in the highest income group. Those in two of the three groups with the smallest housing space also had significant hazard ratios of 2.06 (95% CI 1.16 to 3.65) and 1.68 (95% CI 1.12 to 2.52) when compared with those in group with the largest housing space. These hazard ratios remained largely unchanged after multivariate adjustment for age, gender, baseline cardiovascular disease risk factors, and stroke severity. The analyses did not confirm an association with educational level.

Conclusion

Lower SES has a negative impact on the outcome of first-ever stroke in Nanjing, China. This confirms the need to improve preventive and secondary care for stroke among low SES groups.
Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I'm-Yunity™ (PSP)
Authors: Hsieh Tze-chen , Wu Peili , Park Spencer , Wu Joseph M
Published: September 2006

Background

I'm-Yunity™ (PSP) is a mushroom extract derived from deep-layer cultivated mycelia of the patented Cov-1 strain of Coriolus versicolor (CV), which contains as its main bioactive ingredient a family of polysaccharo-peptide with heterogeneous charge properties and molecular sizes. I'm-Yunity™ (PSP) is used as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. Laboratory studies have shown that I'm-Yunity™ (PSP) enhances immune functions and also modulates cellular responses to external challenges. Recently, I'm-Yunity™ (PSP) was also reported to exert potent anti-tumorigenic effects, evident by suppression of cell proliferation and induction of apoptosis in malignant cells. We investigate the mechanisms by which I'm-Yunity™ (PSP) elicits these effects.

Methods

Human leukemia HL-60 and U-937 cells were incubated with increasing doses of aqueous extracts of I'm-Yunity™ (PSP). Control and treated cells were harvested at various times and analyzed for changes in: (1) cell proliferation and viability, (2) cell cycle phase transition, (3) induction of apoptosis, (4) expression of cell cycle, apoptogenic/anti-apoptotic, and extracellular regulatory proteins.

Results

Aqueous extracts of I'm-Yunity™ (PSP) inhibited cell proliferation and induced apoptosis in HL-60 and U-937 cells, accompanied by a cell type-dependent disruption of the G1/S and G2/M phases of cell cycle progression. A more pronounced growth suppression was observed in treated HL-60 cells, which was correlated with time- and dose-dependent down regulation of the retinoblastoma protein Rb, diminution in the expression of anti-apoptotic proteins bcl-2 and survivin, increase in apoptogenic proteins bax and cytochrome c, and cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product. Moreover, I'm-Yunity™ (PSP)-treated HL-60 cells also showed a substantial decrease in p65 and to a lesser degree p50 forms of transcription factor NF-κB, which was accompanied by a reduction in the expression of cyclooxygenase 2 (COX2). I'm-Yunity™ (PSP) also elicited an increase in STAT1 (signal transducer and activator of transcription) and correspondingly, decrease in the expression of activated form of ERK (extracellular signal-regulated kinase).

Conclusion

Aqueous extracts of I'm-Yunity™ (PSP) induces cell cycle arrest and alterations in the expression of apoptogenic/anti-apoptotic and extracellular signaling regulatory proteins in human leukemia cells, the net result being suppression of proliferation and increase in apoptosis. These findings may contribute to the reported clinical and overall health effects of I'm-Yunity™ (PSP).
Synthesis of acute phase proteins in rats with cirrhosis exposed to lipopolysaccharide
Authors: Nielsen Susanne Schouw , Grøfte Thorbjørn , Tygstrup Niels , Vilstrup Hendrik
Published: September 2006

Background

In patients with cirrhosis, infection is frequent and a leading cause of death. This is secondary to various immunologic abnormalities in both the innate and the adaptive immune system. However, it remains unclear whether cirrhosis affects the inflammatory systemic component of the innate immunity, 'the acute phase response', mostly effectuated by the liver itself. We hypothesized that rats with cirrhosis raise a reduced acute phase response induced by lipopolysaccharide (LPS).

Results

We examined the acute phase response induced by intraperitoneal injection of a low dose of LPS, in sham operated control animals and in rats with liver cirrhosis induced by bile duct ligation (BDL). We measured the serum concentrations of the most important acute phase proteins and their liver tissue gene expressions, assessed by mRNA levels. The BDL-model itself increased the serum concentration of α1-acid glycoprotein (α1AGP) and haptoglobin. LPS was lethal to 25% of the cirrhotic animals and to none of the controls. Twenty-four hours after LPS, the serum concentration of α1AGP and haptoglobin, the mRNA level of these acute phase proteins and of α2-macroglobulin and thiostatin rose to the same level in the animals with cirrhosis and in controls.

Conclusion

In rats with experimental cirrhosis LPS caused high mortality. In the survivors, the cirrhotic liver still synthesized acute phase proteins as the normal liver, indicating a normal hepatic contribution to this part of the acute phase response.
Development of an in vitro model to study clot lysis activity of thrombolytic drugs
Authors: Prasad Sweta , Kashyap Rajpal S , Deopujari Jayant Y , Purohit Hemant J , Taori Girdhar M , Daginawala Hatim F
Published: September 2006

Background

Thrombolytic drugs are widely used for the management of cerebral venous sinus thrombosis patients. Several in vitro models have been developed to study clot lytic activity of thrombolytic drugs, but all of these have certain limitations. There is need of an appropriate model to check the clot lytic efficacy of thrombolytic drugs. In the present study, an attempt has been made to design and develop a new model system to study clot lysis in a simplified and easy way using a thrombolytic drug, streptokinase.

Methods

Whole blood from healthy individuals (n = 20) was allowed to form clots in a pre-weighed sterile microcentrifuge tubes; serum was removed and clot was weighed. After lysis by streptokinase fluid was removed and remnants of clot were again weighed along with the tube. Percentage of Clot lysis was calculated on the basis of the weight difference of microcentrifuge tubes obtained before and after clot lysis.

Results

There was a significant percentage of clot lysis observed when streptokinase was used. On the other hand with water (negative control), minimal (2.5%) clot lysis was observed. There was a significant difference between clot lysis done by streptokinase and water.

Conclusion

Our study could be a rapid and effective methodology to study clot-lytic effect of newly developed drugs as well as known drugs.
Sex, bugs and Haldane's rule: the nematode genus Pristionchus in the United States
Authors: Herrmann Matthias , Mayer Werner E , Sommer Ralf J
Published: September 2006

Background

The nematodePristionchus pacificushas been developed as a satellite organism in evolutionary developmental biology for comparison toCaenorhabditis elegans. Comparative studies have revealed major differences in the regulation of developmental processes betweenP. pacificusandC. elegans. To place evolutionary developmental biology and the observed developmental differences between species in a comprehensive evolutionary context, such studies have to be complemented with ecological aspects. Knowledge about the ecology of the organism in question might indicate specific environmental conditions that can result in developmental adaptations and could account for species differences in development. To this end, we have started to investigate the ecology ofPristionchusnematodes. In recent field studies in Western Europe we found sixPristionchusspecies that are closely associated with scarab beetles and the Colorado potato beetle. ThisPristionchus– beetle association provides the unique opportunity to combine research in evolutionary developmental biology with ecology. However, it remains unknown how general these findings from Europe are on a global scale.

Results

Here, we describe thePristionchusspecies associated with scarab and Colorado potato beetles in the Eastern United States and show striking transatlantic differences and unexpected evolutionary and ecological patterns. Twohundredeighty of 285 (98%) isolates from American scarab beetles belong to fivePristionchusspecies, all of which are different from the European species. We describe four of them as novelPristionchusspecies. The five AmericanPristionchusspecies fall into a single phylogenetic clade and have a male-female (gonochoristic) mode of reproduction, whereas the majority of European isolates are hermaphroditic. Crosses between the two most closely related species,P. aerivorusandP. pseudaerivorusn. sp., follow Haldane's rule in that heterogametic F1 males are inviable. We observedP. aerivorusandP. pseudaerivorusn. sp. coexisting on the same scarab beetle and obtained two cases of F1 hybrids from wild beetles. Finally, the Colorado potato beetle is associated with the same nematode,P. uniformisin the United States and Europe. Given the introduction of the Colorado potato beetle to Europe in 1877, our results suggest thatP. uniformiswas introduced together with its beetle vector.

Conclusion

Taken together, thePristionchus– beetle association provides a powerful tool for studying biodiversity, biogeography, speciation and species invasion on a global scale.
Risk factors for post-ICU red blood cell transfusion: a prospective study
Authors: Marque Sophie , Cariou Alain , Chiche Jean-Daniel , Mallet Vincent Olivier , Pene Frédéric , Mira Jean-Paul , Dhainaut Jean-François , Claessens Yann-Erick
Published: September 2006

Introduction

Factors predictive of the need for red blood cell (RBC) transfusion in the intensive care unit (ICU) have been identified, but risk factors for transfusion after ICU discharge are unknown. This study aims identifies risk factors for RBC transfusion after discharge from the ICU.

Methods

A prospective, monocentric observational study was conducted over a 6-month period in a 24-bed medical ICU in a French university hospital. Between June and December 2003, 550 critically ill patients were consecutively enrolled in the study.

Results

A total of 428 patients survived after treatment in the ICU; 47 (11% of the survivors, 8.5% of the whole population) required RBC transfusion within 7 days after ICU discharge. Admission for sepsis (odds ratio [OR] 341.60, 95% confidence interval [CI] 20.35–5734.51), presence of an underlying malignancy (OR 32.6, 95%CI 3.8–280.1), female sex (OR 5.4, 95% CI 1.2–24.9), Logistic Organ Dysfunction score at ICU discharge (OR 1.45, 95% CI 1.1–1.9) and age (OR 1.06, 95% CI 1.02–1.12) were independently associated with RBC transfusion after ICU stay. Haemoglobin level at discharge predicted the need for delayed RBC transfusion. Use of vasopressors (OR 0.01, 95%CI 0.001–0.17) and haemoglobin level at discharge from the ICU (OR 0.02, 95% CI 0.007–0.09; P < 0.001) were strong independent predictors of transfusion of RBC 1 week after ICU discharge.

Conclusion

Sepsis, underlying conditions, unresolved organ failures and haemoglobin level at discharge were related to an increased risk for RBC transfusion after ICU stay. We suggest that strategies to prevent transfusion should focus on homogeneous subgroups of patients and take into account post-ICU needs for RBC transfusion.
Gene and protein characteristics reflect functional diversity of CD56dim and CD56bright NK cells
Authors: Wendt Katy , Wilk Esther , Buyny Sabine , Buer Jan , Schmidt Reinhold E , Jacobs Roland
Published: September 2006

Recent findings underline the role of NK cell subsets in regulating adaptive immunity. To define characteristics of NK cell subpopulations, purified CD56dim and CD56bright NK cells were analyzed by using gene chip arrays covering more than 39,000 transcripts. Gene profiling revealed resting NK cells to differ in respect to 473 transcripts with 176 exclusively expressed in CD56dim and 130 solely in CD56bright NK cells. Results were compared with array analyses using mRNA obtained from activated CD56dim and CD56bright NK cells. In this approach, NK cell receptors, cytolytic molecules, adhesion structures, and chemokine ligands showed differential expression patterns in the two subpopulations. These data were validated using FACS, RT-qPCR, or cytokine bead array (CBA) techniques. Cytokines produced by CD56dim and CD56bright NK cells were determined using a protein array covering 79 different bioactive mediators. GDNF, IGFBP-1, EGF, and TIMP-2 were detected in both subsets. In contrast, IGFBP-3 and IGF-1 were mainly produced by CD56dim, while GM-CSF, TARC, and TGFβ3 were expressed by CD56bright NK cells. In summary, we report new characteristic features of CD56dim and CD56bright NK cells, further underscoring that they represent independent populations with functionally diverse capabilities. The information on NK cells generated in this study will help to define corresponding NK cell populations in other species that lack CD56 expression on NK cells, such as mice. This will subsequently lead to the establishment of suitable animal models for detailed analysis of NK cell populations in vivo.
Effect of nicotine on IL-18-initiated immune response in human monocytes
Authors: Takahashi Hideo Kohka , Iwagaki Hiromi , Hamano Ryosuke , Yoshino Tadashi , Tanaka Noriaki , Nishibori Masahiro
Published: September 2006

Nicotine is thought to inhibit the production of proinflammatory cytokines from macrophages through an anti-inflammatory pathway that is dependent on nicotinic acetylcholine receptor α7 subunit (α7-nAChR). IL-18, an important proinflammatory cytokine, is reported to induce the expression of adhesion molecules on monocytes, thus enhancing cell-to-cell interactions with T-cells and contributing to IL-18-initiated cytokine production. Accordingly, inhibition of IL-18 suppresses systemic inflammatory responses. In the present study, we found that nicotine inhibited the IL-18-enhanced expression of ICAM-1, B7.2, and CD40 on monocytes, and the production of IL-12, IFN-γ, and TNF-α by PBMC. A nonselective and a selective α7-nAChR antagonist, mecamylamine, and α-bungarotoxin abolished the effects of nicotine, suggesting that this depends on α7-nAChR stimulation. It is reported that nicotine induces prostaglandinE2 (PGE2) production in PBMC through the up-regulation of cyclooxygenase (COX)-2 expression. PGE2 is known to activate the EP2/EP4-receptor, leading to an increase in cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity. Consistent with this, we found that COX-2 and PKA inhibitors prevented the effects of nicotine on adhesion molecule expression and cytokine production, indicating that the mechanism of action of nicotine may be via endogenous PGE2 production.
Surge Capacity for Healthcare Systems: A Conceptual Framework
Authors: Kaji Amy , Koenig Kristi L. , Bey Tareg
Published: September 2006

This report reflects the proceedings of a breakout session, “Surge Capacity: Defining Concepts,” at the 2006 Academic Emergency Medicine Consensus Conference, “Science of Surge Capacity.” Although there are several general descriptions of surge capacity in the literature, there is no universally accepted standard definition specifying the various components. Thus, the objectives of this breakout session were to better delineate the components of surge capacity and to outline the key considerations when planning for surge capacity. Participants were from diverse backgrounds and included academic and community emergency physicians, economists, hospital administrators, and experts in mathematical modeling. Three essential components of surge capacity were identified: staff, stuff, and structure. The focus on enhancing surge capacity during a catastrophic event will be to increase patient‐care capacity, rather than on increasing things, such as beds and medical supplies. Although there are similarities between daily surge and disaster surge, during a disaster, the goal shifts from the day‐to‐day operational focus on optimizing outcomes for the individual patient to optimizing those for a population. Other key considerations in defining surge capacity include psychosocial behavioral issues, convergent volunteerism, the need for special expertise and supplies, development of a standard of care appropriate for a specific situation, and standardization of a universal metric for surge capacity.
The Science of Surge: Detection and Situational Awareness
Authors: McManus John , Huebner Kermit , Scheulen James
Published: September 2006

As part of the broader “science of surge” consensus initiative sponsored by Academic Emergency Medicine, this report addresses the issues of detection and situational awareness as they relate to surge in the practice of emergency medicine. The purpose of this report, and the breakout group that contributed to its content, was to provide emergency physicians and other stakeholders in the emergency medicine community a sense of direction as they plan, prepare for, and respond to surge in their practice.
Research Methods of Inquiry
Authors: Rodgers Joel , Foushee Russell , Terndrup Thomas E. , Gaddis Gary M.
Published: September 2006

Incidents of significant consequence that create surge may require special research methods to provide reliable, generalizable results. This report was constructed through a process of literature review, expert panel discussion at the journal's consensus conference, and iterative development. Traditional clinical research methods that are well accepted in medicine are exceptionally difficult to use for surge incidents because the incidents are very difficult to reliably predict, the consequences vary widely, human behaviors are heterogeneous in response to incidents, and temporal conditions prioritize limited resources to response, rather than data collection. Current literature on surge research methods has found some degree of reliability and generalizability in case‐control, postincident survey methods, and ethnographical designs. Novel methods that show promise for studying surge include carefully validated simulation experiments and survey methods that produce validated results from representative populations. Methodologists and research scientists should consider quasi‐experimental designs and case‐control studies in areas with recurrent high‐consequence incidents (e.g., earthquakes and hurricanes). Specialists that need to be well represented in areas of research include emergency physicians and critical care physicians, simulation engineers, cost economists, sociobehavioral methodologists, and others.
Stage II Colon Cancer Prognosis Prediction by Tumor Gene Expression Profiling
Authors: Barrier Alain , Boelle Pierre-Yves , Roser François , Gregg Jennifer , Tse Chantal , Brault Didier , Lacaine François , Houry Sidney , Huguier Michel , Franc Brigitte , Flahault Antoine , Lemoine Antoinette , Dudoit Sandrine
Published: September 2006

Purpose

This study mainly aimed to identify and assess the performance of a microarray-based prognosis predictor (PP) for stage II colon cancer. A previously suggested 23-gene prognosis signature (PS) was also evaluated.

Patients and Methods

Tumor mRNA samples from 50 patients were profiled using oligonucleotide microarrays. PPs were built and assessed by random divisions of patients into training and validation sets (TSs and VSs, respectively). For each TS/VS split, a 30-gene PP, identified on the TS by selecting the 30 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Two schemes were considered: single-split validation, based on a single random split of patients into two groups of equal size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby patients were repeatedly and randomly divided into TS and VS of various sizes.

Results

The 30-gene PP, identified from group 1 patients, yielded an 80% prognosis prediction accuracy on group 2 patients. MCCV yielded the following average prognosis prediction performance measures: 76.3% accuracy, 85.1% sensitivity, and 67.5% specificity. Improvements in prognosis prediction were observed with increasing TS size. The 30-gene PS were found to be highly-variable across TS/VS splits. Assessed on the same random splits of patients, the previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction accuracy.

Conclusion

Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.