bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-dose inhaled carbon monoxide attenuates the remote intestinal inflammatory response elicited by hindlimb ischemia-reperfusion
Authors: Scott Jeffrey R. , Cukiernik Mark A. , Ott Michael C. , Bihari Aurelia , Badhwar Amit , Gray Daryl K. , Harris Kenneth A. , Parry Neil G. , Potter Richard F.
Published: December 2008

Heme oxygenase (HO) represents the rate-limiting enzyme in the degradation of heme into carbon monoxide (CO), iron, and biliverdin. Recent evidence suggests that several of the beneficial properties of HO, may be linked to CO. The objectives of this study were to determine if low-dose inhaled CO reduces remote intestinal leukocyte recruitment, proinflammatory cytokine expression, and oxidative stress elicited by hindlimb ischemia-reperfusion (I/R). Male mice underwent 1 h of hindlimb ischemia, followed by 3 h of reperfusion. Throughout reperfusion, mice were exposed to AIR or AIR + CO (250 ppm). Following reperfusion, the distal ileum was exteriorized to assess the intestinal inflammatory response by quantifying leukocyte rolling and adhesion in submucosal postcapillary venules with the use of intravital microscopy. Ileum samples were also analyzed for proinflammatory cytokine expression [tumor necrosis factor (TNF)-α and interleukin (IL)-1β] and malondialdehyde (MDA) with the use of enzyme-linked immunosorbent assay and thiobarbituric acid reactive substances assays, respectively. I/R + AIR led to a significant decrease in leukocyte rolling velocity and a sevenfold increase in leukocyte adhesion. This was also accompanied by a significant 1.3-fold increase in ileum MDA and 2.3-fold increase in TNF-α expression. Treatment with AIR + CO led to a significant reduction in leukocyte recruitment and TNF-α expression elicited by I/R; however, MDA levels remained unchanged. Our data suggest that low-dose inhaled CO selectively attenuates the remote intestinal inflammatory response elicited by hindlimb I/R, yet does not provide protection against intestinal lipid peroxidation. CO may represent a novel anti-inflammatory therapeutic treatment to target remote organs following acute trauma and/or I/R injury.
Oxidative Impairment of Mitochondrial Electron Transport Chain Complexes in Rostral Ventrolateral Medulla Contributes to Neurogenic Hypertension
Authors: Chan Samuel H.H. , Wu Kay L.H. , Chang Alice Y.W. , Tai Ming-Hon , Chan Julie Y.H.
Published: December 2008

The role for mitochondrial electron transport chain (ETC) in neurogenic hypertension is unidentified. We evaluated the hypothesis that feedforward depression of mitochondrial ETC functions by superoxide anion (O
2
·−
) and hydrogen peroxide (H
2
O
2
) in rostral ventrolateral medulla (RVLM), a brain stem site that maintains sympathetic vasomotor tone and contributes to oxidative stress and neural mechanism of hypertension. Compared with normotensive Wistar-Kyoto rats, spontaneously hypertensive rats exhibited mitochondrial ETC dysfunctions in RVLM in the forms of depressed complex I or III activity and reduced electron coupling capacity between complexes I and III or II and III. Microinjection of coenzyme Q
10
into RVLM of spontaneously hypertensive rats reversed the depressed ETC activity and augmented O
2
·−
production and hypertensive phenotypes. This mobile electron carrier also antagonized the elevated H
2
O
2
in RVLM and vasopressor responses to complex I (rotenone) or III (antimycin A) inhibitor in Wistar-Kyoto or prehypertensive rats. Intracerebroventricular infusion of angiotensin II promoted mitochondrial ETC dysfunctions in Wistar-Kyoto rats, and coenzyme Q
10
or gene knockdown of the p22
phox
subunit of NADPH oxidase antagonized the resultant elevation of H
2
O
2
in RVLM. Overexpression of superoxide dismutase or catalase in RVLM of spontaneously hypertensive rats by gene transfer reversed mitochondrial dysfunctions and blunted the augmented O
2
·−
and H
2
O
2
in RVLM. We conclude that O
2
·−
- and H
2
O
2
-dependent feedforward impairment of mitochondrial ETC complexes because of predisposed downregulation of superoxide dismutase or catalase and a cross-talk between NADPH oxidase-derived O
2
·−
and ETC enzymes contribute to chronic oxidative stress in the RVLM of spontaneously hypertensive rats, leading to augmented sympathetic vasomotor tone and hypertension.
Mineralocorticoid Receptor Antagonism Attenuates Vascular Apoptosis and Injury via Rescuing Protein Kinase B Activation
Authors: Wei Yongzhong , Whaley-Connell Adam T. , Habibi Javad , Rehmer Jenna , Rehmer Nathan , Patel Kamlesh , Hayden Melvin , DeMarco Vincent , Ferrario Carlos M. , Ibdah Jamal A. , Sowers James R.
Published: December 2008

Emerging evidence indicates that mineralocorticoid receptor (MR) blockade reduces the risk of cardiovascular events beyond those predicted by its blood pressure–lowering actions; however, the underlying mechanisms remain unclear. To investigate whether protection elicited by MR blockade is through attenuation of vascular apoptosis and injury, independently of blood pressure lowering, we administered a low dose of the MR antagonist spironolactone or vehicle for 21 days to hypertensive transgenic Ren2 rats with elevated plasma aldosterone levels. Although Ren2 rats developed higher systolic blood pressures compared with Sprague-Dawley littermates, low-dose spironolactone treatment did not reduce systolic blood pressure compared with untreated Ren2 rats. Ren2 rats exhibited vascular injury as evidenced by increased apoptosis, hemidesmosome-like structure loss, mitochondrial abnormalities, and lipid accumulation compared with Sprague-Dawley rats, and these abnormalities were attenuated by MR antagonism. Protein kinase B activation is critical to vascular homeostasis via regulation of cell survival and expression of apoptotic genes. Protein kinase B serine
473
phosphorylation was impaired in Ren2 aortas and restored with MR antagonism. In vivo MR antagonist treatment promoted antiapoptotic effects by increasing phosphorylation of BAD serine
136
and expression of Bcl-2 and Bcl-xL, decreasing cytochrome
c
release and BAD expression, and suppressing caspase-3 activation. Furthermore, MR antagonism substantially reduced the elevated NADPH oxidase activity and lipid peroxidation, expression of angiotensin II, angiotensin type 1 receptor, and MR in Ren2 vasculature. These results demonstrate that MR antagonism protects the vasculature from aldosterone-induced vascular apoptosis and structural injury via rescuing protein kinase B activation, independent of blood pressure effects.
World Christianity: A Training School for Multiculturalism
Authors: Frederiks Martha
Published: December 2008

Christianity is plural religious tradition: over the centuries and throughout the world's cultures it has taken on a variety of forms and contents. Yet, Christianity also claims to be one tradition, one community. In this article the dialectic relationship between diversity and unity within World Christianity is explored with the view of investigating whether the debate on multiculturalism in Dutch society can benefit from the expertise within the Christian tradition of balancing between diversity and unity.
The 'Great Move of God' in an African Community: A Retrospect of the 1930s Indigenous Pentecostal Revival in Nigeria and Its Impact on Nigerian Pentecostalism
Authors: Fatokun Samson Adetunji
Published: December 2008

The paper examines the 1930s Pentecostal revival in Nigeria that brought Nigerian Pentecostalism onto the global scene. The study is approached from a socio-historical perspective, drawing data from archival search, oral interview and bibliographical search. Among other things, the research brings to the fore the remote and immediate impact of the revival on the Nigerian Church and State. More importantly, the paper locates the rapid growth of Pentecostalism in Nigeria (particularly the much proliferation of churches in the southwest) in the aftermath effects of the 1930s' indigenous Pentecostal revival. That notwithstanding, the paper denounces the undue emphasis on material prosperity which forms the nucleus of Pentecostal crusades/revival in contemporary time and calls on all stake holders to go back to the 'rock from which they were hewn' and purify Pentecostalism in Nigeria of all questionable characteristics.
Changes of Metalloproteinases Profile in Patients With Masked Hypertension
Authors: Papadopoulos D.P. , Thomopoulos C. , Perrea D. , Papazachou U. , Daskalaki M. , Bourantas C. , Votteas V. , Makris T.K.
Published: December 2008

Introduction. The aim of our study was to investigate whether collagen degradation is altered in participants with masked hypertension and whether this alteration could be related to disturbances in the matrix metalloproteinases plasma concentration and to compare the findings with those participants with normal blood pressure levels matched for age, sex, and body mass index. Methods. Twenty-four (11 men, 13 women) participants with masked hypertension [mean age 46 ± 7 years and body mass index 25.9 ± 2.1 kg/m2 (group A)] and 106 healthy normotensives (49 men, 57 women) with normal blood pressure [mean age 44 ± 6 years and body mass index 25.5 ± 2.4 kg/m2 (group B)].

Results. The plasma levels of matrix metalloproteinase-9 were significantly higher, while the levels of tissue inhibitors of metalloproteinases-1 and -4 were significantly lower in group A compared with group B (matrix metalloproteinase-9: 569 ± 135 vs. 282 ± 117 ng/mL, TIMP-1: 169 ± 42 vs. 230 ± 37 ng/mL, P < .01, and TIMP-4: 2.1 ± 1.3 vs. 4.2 ± 1.98 ng/mL, P < .04, respectively).

Conclusions. Patients with masked hypertension had significantly increased matrix metalloproteinase-9 plasma levels and significantly decreased plasma levels of tissue inhibitors of metalloproteinases-1 and -4 compared with participants with normal blood pressure. These findings need further investigation.
Operationalizing Self-Efficacy, Related Social Cognitive Variables, and Moderating Effects
Authors: O'Sullivan Deirdre , Strauser David R.
Published: December 2008

Self-efficacy, a core construct of Bandura's social cognitive theory, has wide appeal and usefulness in the health and social sciences. Self-efficacy is frequently used across disciplines to assess an individual's beliefs about her likelihood to engage in a certain behavior. Because of the behavioral-change approaches common in rehabilitation counseling interventions, self-efficacy is an important construct to operationalize, measure, and apply for best research and clinical outcomes. Several factors contribute to inaccurate or inappropriate assessment, measurement, interpretation, and application of this important construct; numerous scales used to measure efficacy, various contexts, related constructs, and moderating effects of efficacy make best use of efficacy measurement and application difficult. This article outlines the theory of self-efficacy, distinguishes its closely related constructs, summarizes common moderating effects, and provides important considerations for clinical practice and research.
Price Bundling and Travel Product Pricing Practices Used by Online Channels of Distribution
Authors: Kim Jinhoo , Bojanic David C. , Warnick Rodney B.
Published: December 2008

Price bundling is one of the most prevalent marketing practices in many industries, including hospitality and travel. Virtually all types of firms in the hospitality and travel industry, from suppliers such as hotels and airlines to intermediaries such as travel agents, are encouraging customers to purchase travel “packages” rather than a single component of travel to save money and streamline the purchasing process. The purpose of this research is to determine whether the practice of price bundling by online travel agents results in actual monetary savings for consumers (i.e., lower prices) relative to the prices charged by individual service providers (i.e., hotels and airlines) through their own online Web sites. The results indicate that there are monetary savings in the form of lower prices realized by consumers who purchase bundled offerings from online travel agents, and there is an interaction effect between channel and hotel class.
Race as a Moderator of the Relationship Between Religiosity and Political Alignment
Authors: Cohen Adam B. , Malka Ariel , Hill Eric D. , Thoemmes Felix , Hill Peter C. , Sundie Jill M.
Published: December 2008

Religiosity, especially religious fundamentalism, is often assumed to have an inherent connection with conservative politics. This article proposes that the relationship varies by race in the United States. In Study 1, race moderated the relationships between religiosity indicators and political alignment in a nationally representative sample. In Study 2, the effect replicated in a student sample with more reliable measures. Among both Black and Latino Americans, the relationship between religiosity and conservative politics is far weaker than it is among White Americans, and it is sometimes altogether absent. In Study 3, a tradition-focused view of religion was found to more strongly mediate the link between religiosity and political attitudes among Whites than it did among Blacks and Latinos. It is argued that the relationship between religiosity and political alignment is best understood as a product of cultural—historical conditions associated with group memberships.
Lay persons' and professionals' nutrition-related vocabularies and their matching to a general and a specific thesaurus
Authors: Poikonen Tuula , Vakkari Pertti
Published: December 2008

This study examines the differences between expressions used by lay persons and professionals in nutrition-related questions and answers, and to what degree General Finnish Ontology (GFO) and a medical thesaurus (FinMeSH) cover these expressions. Fifty question—answer pairs were collected in an electronic answering service. Nutrition-related concepts and their expressions with their semantic relations were identified. The vocabularies of lay persons and professionals were found to be quite similar. This hints that a special consumer health vocabulary in the field of nutrition is not needed. GFO covered 32% of all expressions in questions and 37% of expressions in answers. FinMeSH covered 33% of expressions in both groups. The overlapping match of the thesauri was low, 25% in both questions and in answers. GFO and FinMeSH were found to be poor tools for supporting users in expressing nutrition-related information needs. GFO seemed not to form a covering bridge to FinMeSH.
Using Research Evidence to Inform and Evaluate Early Childhood Intervention Practices
Authors: Dunst Carl J. , Trivette Carol M.
Published: December 2008

This article includes descriptions of a process used to conduct practice-based research syntheses and the manner in which synthesis findings are used to inform and evaluate early childhood intervention practices. The main focus of a practice-based research synthesis is the unbundling of an intervention practice to identify those practice characteristics that are associated with desired outcomes and benefits. Also described are how the characteristics identified as most important are used to develop evidence-based practices and how the characteristics can be used as benchmarks to assess the likelihood that an untested practice will be effective. The article concludes with a discussion of the tension between research and practice and how that tension might be mitigated.
“You Can't Bite the Hand . . .”
Authors: Morgaine Karen
Published: December 2008

This article examines whether the international “women's rights as human rights” movement has influenced the field of domestic violence in the United States and the possible barriers to redefining domestic violence as a violation of human rights. The qualitative study that is presented was based on semistructured interviews with key individuals throughout the United States who work in national organizations on issues of domestic violence and/or human rights. The findings focus on the manner in which power situated within the state would result in significant barriers to reframing domestic violence related to themes of resonance, U.S. exceptionalism, funding, and the criminal justice system.
The Time- and Context-Contingent Nature of Intersectionality and Interlocking Oppressions
Authors: Hulko Wendy
Published: December 2008

This article addresses the theoretical paradigm of intersectionality and interlocking oppressions, focusing on its evolution over time and place and application to the everyday lives of women. The objective is both to honor the roots of intersectional scholarship and to demonstrate the temporal and spatial nature of oppression and privilege. Theoretical concepts are illustrated by narratives from women who have crossed different sociocultural contexts and phases of the life course. This dialectical and self-reflexive intersectional analysis focuses not only on oppression but also on privilege and demonstrates that intersectionality and interlocking oppressions are time and context contingent, rather than fixed and ahistorical.
Survivors of Stalking
Authors: Cox Linda , Speziale Bette
Published: December 2008

The literature on stalking inadequately incorporates the voices of female survivors whose lived experiences escalated to the point of violence or the threat of lethal violence by male perpetrators. To address this gap in the literature and include the insights of survivors in the ongoing discourse about stalking, the authors sought the perspectives of nine heterosexual female survivors. The stories of these women, evident in the presentation of the six themes and deviant case that emerged from the data, provide a richer and fuller understanding of this form of interpersonal violence. Implications for practice are discussed.
“I Can't Cry and Run at the Same Time”
Authors: Leedy Gail
Published: December 2008

This qualitative study explores the beneficial functions of distance running for women. In-depth interviews were conducted with five women runners who reported that they had used distance running as a mechanism to help them cope during a time of emotional stress. A case method analysis of the narratives yielded both common themes and unique processes and resulted in a model that integrates running for the promotion of well-being and empowerment with therapeutic components. Implications for social work practice emphasize the importance of supporting exercise as a means of preventing and treating stress-induced disorders.
Teaching Methodology to Distance Education Students Using Rich-Media and Computer Simulation
Authors: Vasu Michael L. , Ozturk Ali O.
Published: December 2008

This article addresses the two major issues involved in the teaching of an introductory methodology course versus face-to-face instruction. The first issue incorporates a rich-media solution, specifically streaming video, to precede traditional notes on any topic and second the use of a computer simulation software created by the authors, which can be placed on a matriculated distance education student's desktop remotely, without the legal or logistical problems of using commercial software, for example, Statistical Package for the Social Sciences (SPSS) or Statistical Analysis Software (SAS). Technical and pedagogical dimensions of these particular issues are discussed as well.
Health-Related Quality of Life in Community-Dwelling Older Whites and African Americans
Authors: Yuri Jang  , Chiriboga David A. , Borenstein Amy R. , Small Brent J. , Mortimer James A.
Published: December 2008

Objective: This study assesses structural and functional characteristics of Short Form-36 Health Survey (SF-36) domains using community-based samples of older Whites and African Americans. Although the eight domains of the SF-36 have by convention been collapsed into two summary categories— physical health and mental health—the authors examine a three-factor model including physical health, mental health, and general well-being. They hypothesized that the general well-being factor would be a mediator between physical and mental health in both groups. Method: Analyses using structural equation modeling provide support for the approach. Results: In both White and African American samples, the three-factor model demonstrated a better fit than the two-factor model. Also, in both groups, general well-being mediated the relationship between physical health and mental health. Discussion: Findings suggest that general well-being serves as an intervening step between physical and mental health in both White and African American older adults.
In quest of publicity: the science—media partnership of the Galathea Deep Sea Expedition from 1950 to 1952
Authors: Nielsen Kristian Hvidtfelt
Published: December 2008

The Galathea Deep Sea Expedition from 1950 to 1952 combined oceanographic research with simultaneous science reporting and strategically seeking publicity. In effect, the expedition organizers ventured into a science—media partnership. From the beginning, reporting scientific exploration to the general public at home and abroad was considered an essential part of the expedition. Combining scientific objectives with publicity concerns, the expedition built on boundary work performed by boundary workers separating science from the media. Several boundary objects were mobilized to facilitate interactions across the cultural border between scientists and journalists. In particular, the mythological sea serpent domesticated by scientists and fully adopted by journalists played an important role in aligning the scientific aspects of the expedition with publicity and science reporting. The historical narrative of the expedition feeds into contemporary discussions about the dominant discourse on science and the media.
Baclofen as an Adjuvant Analgesic for Cancer Pain
Authors: Yomiya Kinomi , Matsuo Naoki , Tomiyasu Shiro , Yoshimoto Tetsusuke , Tamaki Tomohiro , Suzuki Tsutomu , Matoba Motohiro
Published: December 2008

Purpose: Baclofen is a g-aminobutyric acid receptor agonist commonly used for managing many types of neuropathic pain. The effect of baclofen on cancer pain has not previously been studied. This retrospective study evaluated the efficacy of baclofen in patients with cancer pain.

Methods: We reviewed the medical records of all patients given baclofen orally as an analgesic for cancer at 5 institutions.

Result: Twenty-five patients received 10 to 40 mg of baclofen for cancer pain relief. Twenty patients have undergone neuropathic pain such as paroxysmal or lancing, sharp, or like an electric shock. Baclofen was effective in 21 of 25 patients and significantly reduced Numeric Rating Scale (pain score, 0-10; P < .0001). Nine patients reported mild adverse events: none of these 9 patients had to discontinue baclofen due to adverse events.

Conclusion: Our findings suggest that baclofen may be a useful adjuvant analgesic in the treatment of cancer pain.
End-of-life Care: An Interdisciplinary Perspective
Authors: Viola Deborah , Leven David C. , LePere Jean C.
Published: December 2008

The Institute of Medicine has described the ``deathdenying character of American society'' and surely, there is an opportunity to change this character. Despite our understandable concern with costs, end-of-life care options must be variously considered from economic, ethical, and legislative perspectives. We consider these multiple perspectives of end-of-life care in an attempt to inform current thinking on the part of legislators, policy makers, providers, patients, families/ caregivers, and insurers on the issue of end-of-life care. Society must be educated to understand that death can be peaceful and that end-of-life planning and care is an integral part of society's continuum of care. Enabling affordability, expanding availability, and ensuring access are the only ways of realizing that outcome.
Contextual Inhibitors of Employee Creativity in Organizations
Authors: Jin Nam Choi  , Anderson Troy A. , Veillette Anick
Published: December 2008

This study highlights the importance of negative predictors of employee creativity. The authors identified a set of work environment characteristics that may inhibit employee creativity. Using data collected from 123 Canadian employees in various industries, the authors empirically tested the relationships between these inhibiting factors and peer-rated creative performance. Aversive leadership and unsupportive organizational climate were negatively related to creativity, whereas close monitoring was positively associated with creativity. Interaction analyses indicate that creative ability of employees may either enhance or attenuate the detrimental effects of inhibitory contextual factors. Complementing the existing studies that have largely focused on facilitators of creativity, the present study introduces a more balanced perspective to the organizational creativity literature by examining inhibitory contextual factors.
The Development of Public Perception Research in the Genomics Field
Authors: Pin Renske R. , Gutteling Jan M.
Published: December 2008

This article describes a meta-analysis that was conducted on the subjects of published academic research on the public perception of genomics. In total, 451 journal articles were analyzed, all published between 1970 and 2006 and sampled from the databases Web of Science and Scopus. Results indicate the increasing popularity of research on this topic in the last decade, which reflects the same curve as media coverage of the new technology. Many authors study the public perception of genomics, but only a small number are productive. There is a strong focus on food and agriculture genomics and a separate field of authors and journals for medical genomics. The authors make several recommendations for future developments in the public perception of genomics.
Struggling to Reconnect: Women's Perspectives on Alcohol Dependence, Violence, and Sexual Function
Authors: Ambrogne Sobczak Janet
Published: December 2008

Until recently, substance use disorders and sexual function were two areas in which women received comparatively less attention then men. Recent studies have challenged sexual stereotypes about women who drink and use other substances. This study explores the experiences of women dependent on alcohol and/or other substances who have stopped their use. These women were subjected to significant abuse during both childhood and adulthood. A pattern of using alcohol and other substances as a means of managing negative feelings, disconnecting from abuse, reconnecting to form new relationships, and disconnecting from subsequent abuse was prominent in the women's stories. The women in this study also experienced problems with sexual function both while using and following cessation of use. Findings highlight the complex relationships among substance abuse, trauma, and sexual problems as well as the importance of routinely assessing for sexual problems. Suggestions for treatment and future research are offered. J Am Psychiatr Nurses Assoc, 2009; 14(6), 421-428.
Human Trafficking: Implications for the Role of the Advanced Practice Forensic Nurse
Authors: Cole Helen
Published: December 2008

Human trafficking is internationally recognized as a widespread violation of human rights. This article defines and gives a detailed historical account of the political and social issues surrounding human trafficking. The article explains the role of the advanced practice forensic nurse in recognizing and addressing the needs of victims of human trafficking. The developing roles of the advanced practice psychiatric forensic nurse in collaboration with law enforcement and health care professionals are described with the ultimate goal of restoring the lives of victims of human trafficking. J Am Psychiatr Nurses Assoc, 2009; 14(6), 462-470.
A New Look at Emotional Intelligence: A Dual-Process Framework
Authors: Fiori Marina
Published: December 2008

In this article, the author provides a framework to guide research in emotional intelligence. Studies conducted up to the present bear on a conception of emotional intelligence as pertaining to the domain of consciousness and investigate the construct with a correlational approach. As an alternative, the author explores processes underlying emotional intelligence, introducing the distinction between conscious and automatic processing as a potential source of variability in emotionally intelligent behavior. Empirical literature is reviewed to support the central hypothesis that individual differences in emotional intelligence may be best understood by considering the way individuals automatically process emotional stimuli. Providing directions for research, the author encourages the integration of experimental investigation of processes underlying emotional intelligence with correlational analysis of individual differences and fosters the exploration of the automaticity component of emotional intelligence.
Enzymes, Trophoblasts, and Cancer: The Afterlife of an Idea (1924-2008)
Authors: Moss Ralph W.
Published: December 2008

In the early 20th century, advocacy of the enzyme therapy of cancer was primarily the work of one man, John Beard, DSc (1858-1924). He and his collaborators made a determined effort to establish this mode of therapy, especially in the years 1905 to 1911. Despite a brief flowering of international interest, Beard's efforts came to naught. During the 20th century, there was a succession of American researchers who continued to investigate this topic. This included Marshall William McDuffie, MD (1882-1945), Frank LeForest Morse, MD (1876-1953), Franklin Lloyd Shively, MD (1887-1971), and William Donald Kelley (1926-2005). In central Europe, India, and other parts of the globe, the use of pancreatic enzymes as an adjuvant treatment for cancer has become a fairly routine practice, at least among those doctors who utilize complementary and alternative medicine (CAM). It is also a well-established method for reducing inflammation and mitigating the adverse effects of cytotoxic treatment.
Of Germ Cells, Trophoblasts, and Cancer Stem Cells
Authors: Burleigh Angela R.
Published: December 2008

The trophoblastic theory of cancer, proposed in the early 1900s by Dr John Beard, may not initially seem relevant to current cancer models and treatments. However, the underpinnings of this theory are remarkably similar to those of the cancer stem cell (CSC) theory. Beard noticed that a significant fraction of germ cells never reach their final destination as they migrate during embryonic development from the hindgut to the germinal ridge. In certain situations, upon aberrant stimulation, these vagrant germ cells are able to generate tumors. Simplistically, the CSC theory surmises that a small population of tumorigenic cells exists, which initiate and maintain tumors, and these cells have a likely origin in normal stem cells. Both these theories are based on the potential of a single primitive cell to form a tumor. This has a major implication for cancer therapy, in that only a small percentage of cells need to be targeted to ablate a tumor.
Differential Effects of Serine Proteases on the Migration of Normal and Tumor Cells: Implications for Tumor Microenvironment
Authors: Elzer Kirsten L. , Heitzman Deborah A. , Chernin Mitchell I. , Novak Josef F.
Published: December 2008

The supporting role of proteases in tumor progression and invasion is well known; however, the use of proteases as therapeutic agents has also been demonstrated. In this article, the authors report on the differential effects of exogenous serine proteases on the motility of tumor and normal cells. The treatment of normal and tumor cells with a single dose of pancreatic serine proteases, trypsin (TR) and chymotrypsin (CH), leads to a concentration-dependent response by cells, first accelerating and then slowing mobility. Tumor cells are 10 to 20 times more sensitive to exogenous TR/CH, suggesting that a single dose of proteases may cause discordant movements of normal and tumor cells within the tumor environment. The inhibitory effects of TR on cell motility are contradicted by thrombin (TH), particularly in the regulation of normal cells' migration. The purpose of this investigation was to ascertain the role of protease-activated receptors (PARs) in terms of normal and tumor cell motility. Duplicate treatments with proteases resulted in diminished mobility of both normal and tumor cells. Repeated application of TR and TH in 1-hour treatment intervals initially desensitizes cell surface PARs. However, cell surface PARs reappear regardless of subsequent protease treatments in both normal and tumor cells. The resensitization process is retarded in tumor cells when compared with normal cells. This is evidenced by lower expression of PARs as well as by their relocalization at the tumor cell surfaces. Under these conditions, normal cells remain responsive to exogenous proteases in terms of cell motility. Exogenous proteases do not modulate motility of repeatedly stimulated tumor cells, and consequently, the migration of tumor cells appears disconnected from the PAR signaling pathways. The use of activating peptides in lieu of the cognate proteases for a given PAR system indicated that proteases may act through additional targets not regulated by PAR signaling. We hypothesize that the divergent migration patterns of normal and tumor cells due to exposure to proteases is in part mediated by PARs. Thus, treatment with exogenous proteases may cause rearrangement of the tumor and stromal cells within the tumor microenvironment. Such topographical effects may lead to the inhibition of tumor progression and metastasis development.
EST based phylogenomics of Syndermata questions monophyly of Eurotatoria
Authors: Witek Alexander , Herlyn Holger , Meyer Achim , Boell Louis , Bucher Gregor , Hankeln Thomas
Published: December 2008

Background

The metazoan taxon Syndermata comprising Rotifera (in the classical sense of Monogononta+Bdelloidea+Seisonidea) and Acanthocephala has raised several hypotheses connected to the phylogeny of these animal groups and the included subtaxa. While the monophyletic origin of Syndermata and Acanthocephala is well established based on morphological and molecular data, the phylogenetic position of Syndermata within Spiralia, the monophyletic origin of Monogononta, Bdelloidea, and Seisonidea and the acanthocephalan sister group are still a matter of debate. The comparison of the alternative hypotheses suggests that testing the phylogenetic validity of Eurotatoria (Monogononta+Bdelloidea) is the key to unravel the phylogenetic relations within Syndermata. The syndermatan phylogeny in turn is a prerequisite for reconstructing the evolution of the acanthocephalan endoparasitism.

Results

Here we present our results from a phylogenomic approach studying i) the phylogenetic position of Syndermata within Spiralia, ii) the monophyletic origin of monogononts and bdelloids and iii) the phylogenetic relations of the latter two taxa to acanthocephalans. For this analysis we have generated EST libraries of Pomphorhynchus laevis, Echinorhynchus truttae (Acanthocephala) and Brachionus plicatilis (Monogononta). By extending these data with database entries of B. plicatilis, Philodina roseola (Bdelloidea) and 25 additional metazoan species, we conducted phylogenetic reconstructions based on 79 ribosomal proteins using maximum likelihood and bayesian approaches. Our findings suggest that the phylogenetic position of Syndermata within Spiralia is close to Platyhelminthes, that Eurotatoria are not monophyletic and that bdelloids are more closely related to acanthocephalans than monogononts.

Conclusion

Mapping morphological character evolution onto molecular phylogeny suggests the (partial or complete) reduction of the corona and the emergence of a retractable anterior end (rostrum, proboscis) before the separation of Acanthocephala. In particular, the evolution of a rostrum might have been a key event leading to the later evolution of the acanthocephalan endoparasitism, given the enormous relevance of the proboscis for anchoring of the adults to the definitive hosts' intestinal wall.
Proinflammatory effect in whole blood by free soluble bacterial components released from planktonic and biofilm cells
Authors: Oscarsson Jan , Karched Maribasappa , Thay Bernard , Chen Casey , Asikainen Sirkka
Published: December 2008

Background

Aggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressive forms of periodontitis. Increasing evidence points to a link between periodontitis and cardiovascular diseases, however, the underlying mechanisms are poorly understood. This study investigated the pathogenic potential of free-soluble surface material, released from live planktonic and biofilm A. actinomycetemcomitans cells.

Results

By employing an ex vivo insert model (filter pore size 20 nm) we demonstrated that the A. actinomycetemcomitans strain D7S and its derivatives, in both planktonic and in biofilm life-form, released free-soluble surface material independent of outer membrane vesicles. This material clearly enhanced the production of several proinflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, MIP-1β) in human whole blood, as evidenced by using a cytokine antibody array and dissociation-enhanced-lanthanide-fluorescent-immunoassay. In agreement with this, quantitative real-time PCR indicated a concomitant increase in transcription of each of these cytokine genes. Experiments in which the LPS activity was blocked with polymyxin B showed that the stimulatory effect was only partly LPS-dependent, suggesting the involvement of additional free-soluble factors. Consistent with this, MALDI-TOF-MS and immunoblotting revealed release of GroEL-like protein in free-soluble form. Conversely, the immunomodulatory toxins, cytolethal distending toxin and leukotoxin, and peptidoglycan-associated lipoprotein, appeared to be less important, as evidenced by studying strain D7S cdt/ltx double, and pal single mutants. In addition to A. actinomycetemcomitans a non-oral species, Escherichia coli strain IHE3034, tested in the same ex vivo model also released free-soluble surface material with proinflammatory activity.

Conclusion

A. actinomycetemcomitans, grown in biofilm and planktonic form, releases free-soluble surface material independent of outer membrane vesicles, which induces proinflammatory responses in human whole blood. Our findings therefore suggest that release of surface components from live bacterial cells could constitute a mechanism for systemic stimulation and be of particular importance in chronic localized infections, such as periodontitis.
DNA-microarrays identification of Streptococcus mutans genes associated with biofilm thickness
Authors: Shemesh Moshe , Tam Avshalom , Kott-Gutkowski Miriam , Feldman Mark , Steinberg Doron
Published: December 2008

Background

A biofilm is a complex community of microorganisms that develop on surfaces in diverse environments. The thickness of the biofilm plays a crucial role in the physiology of the immobilized bacteria. The most cariogenic bacteria, mutans streptococci, are common inhabitants of a dental biofilm community. In this study, DNA-microarray analysis was used to identify differentially expressed genes associated with the thickness of S. mutans biofilms.

Results

Comparative transcriptome analyses indicated that expression of 29 genes was differentially altered in 400- vs. 100-microns depth and 39 genes in 200- vs. 100-microns biofilms. Only 10 S. mutans genes showed differential expression in both 400- vs. 100-microns and 200- vs. 100-microns biofilms. All of these genes were upregulated.

As sucrose is a predominant factor in oral biofilm development, its influence was evaluated on selected genes expression in the various depths of biofilms. The presence of sucrose did not noticeably change the regulation of these genes in 400- vs. 100-microns and/or 200- vs. 100-microns biofilms tested by real-time RT-PCR.

Furthermore, we analyzed the expression profile of selected biofilm thickness associated genes in the luxS
- mutant strain. The expression of those genes was not radically changed in the mutant strain compared to wild-type bacteria in planktonic condition. Only slight downregulation was recorded in SMU.2146c, SMU.574, SMU.609, and SMU.987 genes expression in luxS
- bacteria in biofilm vs. planktonic environments.

Conclusion

These findings reveal genes associated with the thickness of biofilms of S. mutans. Expression of these genes is apparently not regulated directly by luxS and is not necessarily influenced by the presence of sucrose in the growth media.
What needs to change to increase chlamydia screening in general practice in Australia? The views of general practitioners
Authors: Hocking Jane S , Parker Rhian M , Pavlin Natasha , Fairley Christopher K , Gunn Jane M
Published: December 2008

Background

Australia is considering implementing a chlamydia screening program in general practice. The views of general practitioners (GPs) are necessary to inform the design of the program. This paper aimed to investigate Australian GPs' views on how chlamydia screening could work in the Australian context.

Methods

This project used both qualitative interviews and a quantitative questionnaire. GPs were randomly selected from a national database of medical practitioners for both the qualitative and quantitative components. Semi-structured interviews were conducted with GPs and a thematic analysis conducted. The results of the interviews were used to design a quantitative postal questionnaire for completion by a larger sample of GPs. Up to three reminders were sent to non-responders.

Results

Twenty one GPs completed an interview and 255 completed the postal questionnaire. The results of the postal survey were in strong concordance with those of the interview. GPs identified a number of barriers to increased screening including lack of time, knowledge of GPs and the public about chlamydia, patient embarrassment and support for partner notification. GPs felt strongly that screening would be easier if there was a national program and if the public and GPs had a greater knowledge about chlamydia. Incentive payments and mechanisms for recall and reminders would facilitate screening. Greater support for contact tracing would be important if screening is to increase.

Conclusion

Chlamydia screening in general practice is acceptable to Australian GPs. If screening is to succeed, policy makers must consider the facilitators identified by GPs.
A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell lymphoma of the pleura
Authors: Hatzibougias Dimitrios , Bobos Mattheos , Karayannopoulou Georgia , Karkavelas Georgios , Karapanagiotidis Georgios T , Foroulis Christophoros N , Kostopoulos Ioannis
Published: December 2008

Background

Coexistence of adenocarcinoma and mantle cell lymphoma in the same or different anatomical sites is extremely rare. We present a case of incidental discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the pleura, during an axillary thoracotomy performed for a benign condition.

Case presentation

A 73-year old male underwent bullectomy and apical pleurectomy for persistent pneumothorax. A bulla of the lung apex was resected en bloc with a scar-like lesion of the lung, which was located in proximity with the bulla origin, by a wide wedge resection. Histologic examination of the stripped-off parietal pleura and of the bullectomy specimen revealed the synchronous occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization assays were performed. The morphologic, immunophenotypic and genetic findings supported the diagnosis of primary lung adenocarcinoma (papillary subtype) coexisting with a non-Hodgkin, B-cell lineage, mantle cell lymphoma involving both, visceral and parietal pleura and without mediastinal lymph node involvement. The neoplastic lymphoid cells showed the characteristic immunophenotype of mantle cell lymphoma and the translocation t(11;14). The patient received 6 cycles of chemotherapy, while pulmonary function tests precluded further pulmonary parenchyma resection (lobectomy) for his adenocarcinoma. The patient is alive and without clinical and radiological findings of local recurrence or distant relapse from both tumors 14 months later.

Conclusion

This is the first reported case of a rare tumoral combination involving simultaneously lung and pleura, emphasizing at the incidental discovery of the two coexisting neoplasms during a procedure performed for a benign condition. Any tissue specimen resected during operations performed for non-tumoral conditions should be routinely sent for pathologic examination.
Fgf2 is expressed in human and murine embryonic choroid plexus and affects choroid plexus epithelial cell behaviour
Authors: Greenwood Sarah , Swetloff Adam , Wade Angela M , Terasaki Tetsuya , Ferretti Patrizia
Published: December 2008

Background

Although fibroblast growth factor (Fgf) signalling plays crucial roles in several developing and mature tissues, little information is currently available on expression of Fgf2 during early choroid plexus development and whether Fgf2 directly affects the behaviour of the choroid plexus epithelium (CPe). The purpose of this study was to investigate expression of Fgf2 in rodent and human developing CPe and possible function of Fgf2, using in vitro models. The application of Fgf2 to brain in vivo can affect the whole tissue, making it difficult to assess specific responses of the CPe.

Methods

Expression of Fgf2 was studied by immunohistochemistry in rodent and human embryonic choroid plexus. Effects of Fgf2 on growth, secretion, aggregation and gene expression was investigated using rodent CPe vesicles, a three-dimensional polarized culture model that closely mimics CPe properties in vivo, and rodent CPe monolayer cultures.

Results

Fgf2 was present early in development of the choroid plexus both in mouse and human, suggesting the importance of this ligand in Fgf signalling in the developing choroid plexus. Parallel analysis of Fgf2 expression and cell proliferation during CP development suggests that Fgf2 is not involved in CPe proliferation in vivo. Consistent with this observation is the failure of Fgf2 to increase proliferation in the tri-dimensional vesicle culture model. The CPe however, can respond to Fgf2 treatment, as the diameter of CPe vesicles is significantly increased by treatment with this growth factor. We show that this is due to an increase in cell aggregation during vesicle formation rather than increased secretion into the vesicle lumen. Finally, Fgf2 regulates expression of the CPe-associated transcription factors, Foxj1 and E2f5, whereas transthyretin, a marker of secretory activity, is not affected by Fgf2 treatment.

Conclusion

Fgf2 expression early in the development of both human and rodent choroid plexus, and its ability to modulate behaviour and gene expression in CPe, supports the view that Fgf signalling plays a role in the maintenance of integrity and function of this specialized epithelium, and that this role is conserved between rodents and humans.