bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirement of Activated Cdc42-Associated Kinase for Survival of v-Ras-Transformed Mammalian Cells
Authors: Nur-E-Kamal Alam , Zhang Ailing , Keenan Susan M. , Wang Xin I. , Seraj Jabed , Satoh Takaya , Meiners Sally , Welsh William J.
Published: September 2005

Activated Cdc42-associated kinase (ACK) has been shown to be an important effector molecule for the small GTPase Cdc42. We have shown previously an essential role for Cdc42 in the transduction of Ras signals for the transformation of mammalian cells. In this report, we show that the ACK-1 isoform of ACK plays a critical role in transducing Ras-Cdc42 signals in the NIH 3T3 cells. Overexpression of a dominant-negative (K214R) mutant of ACK-1 inhibits Ras-induced up-regulation of c-fos and inhibits the growth of v-Ras-transformed NIH 3T3 cells. Using small interfering RNA, we knocked down the expression of ACK-1 in both v-Ha-Ras-transformed and parental NIH 3T3 cells and found that down-regulation of ACK-1 inhibited cell growth by inducing apoptosis only in v-Ha-Ras-transformed but not parental NIH 3T3 cells. In addition, we studied the effect of several tyrosine kinase inhibitors and found that PD158780 inhibits the kinase activity of ACK-1 in vitro. We also found that PD158780 inhibits the growth of v-Ha-Ras-transformed NIH 3T3 cells. Taken together, our results suggest that ACK-1 kinase plays an important role in the survival of v-Ha-Ras-transformed cells, suggesting that ACK-1 is a novel target for therapies directed at Ras-induced cancer.
Urinary Prostasin
Authors: Olivieri Oliviero , Castagna Annalisa , Guarini Patrizia , Chiecchi Laura , Sabaini Gherardo , Pizzolo Francesca , Corrocher Roberto , Righetti Pier Giorgio
Published: September 2005

Prostasin is a serine peptidase hypothesized to regulate epithelial sodium channel (ENaC) activity in animals or on in vitro cultured cells. We investigated whether urinary prostasin may be a candidate marker of ENaC activation in humans. We studied 10 healthy volunteers and 8 hypertensive patients with raised aldosterone-to-renin ratio before and after spironolactone or saline/Florinef suppression test, respectively. Four healthy subjects were also studied before and after saline. Urinary prostasin was evaluated by SDS-PAGE, 2D maps, and Western blotting. Every sample of normotensive individuals was compared with the corresponding sample of urine collected after spironolactone or saline; every sample of hypertensive patients was compared with the corresponding sample of urine collected after saline or Florinef. Prostasin was detectable in all subjects regardless of gender, dietary sodium intake, and spironolactone treatment. Spironolactone (100 mg) increased urinary Na
+
/K
+
ratio and decreased urinary prostasin in normotensives in whom the renin/aldosterone axis was activated by a low Na
+
intake, but it was ineffective in individuals with high Na
+
intake. Saline infusion also reduced prostasin in normotensive subjects. In contrast, prostasin paradoxically increased in urine of patients affected by primary aldosteronism after volume expansion. By 2D immunoblotting, several protein isoforms were observed, some of them being overexpressed after inhibition tests in patients with primary aldosteronism. In addition to a “basal” aliquot of prostasin, constitutively released in human urine regardless of sodium balance and aldosterone activation, there exists a second “aldosterone-responsive” aliquot modulated by Na
+
intake and potentially suitable as candidate marker of ENaC activation.
Generation of Reactive Oxygen Species by Neutrophils and Endothelial Cell Injury in Normal and Preeclamptic Pregnancies
Authors: Tsukimori Kiyomi , Fukushima Kotaro , Tsushima Akitoshi , Nakano Hitoo
Published: September 2005

The aim of this study was to investigate the role of neutrophil-derived reactive oxygen species on endothelial cell dysfunction in preeclampsia. We first assessed the correlation between nitrite and superoxide anion production in normal nonpregnant (n=10), normal pregnant (n=15), and preeclamptic women (n=12). We then examined neutrophil-mediated oxygen radical damage to human umbilical vein endothelial cells in vitro. Neutrophil superoxide release was measured by cytochrome C reduction; nitrite release was measured by the modified Griess reaction, and endothelial cell injury was measured by
51
Cr release.
N
-formyl-methionyl-leucyl-phenylalanine–stimulated superoxide release by neutrophils was significantly increased in women with preeclampsia compared with the other 2 groups. Nitrite release by neutrophils was significantly decreased in preeclampsia compared with normal pregnancy. When neutrophils were pretreated with superoxide dismutase, nitrite release by neutrophils did not differ between normal pregnancy and preeclampsia, suggesting that excess superoxide anion in preeclampsia could reduce bioavailability of nitric oxide through neutrophil autocrine function. Neutrophil-mediated endothelial cell injury was significantly greater in women with preeclampsia than in the other 2 groups. Hydrogen peroxide was important in neutrophil-mediated endothelial cell injury in preeclampsia as catalase inhibited endothelial cell injury. When neutrophils were pretreated with N
G
-nitro-
l
-arginine methyl ester, neutrophil-mediated endothelial cell injury in preeclampsia was decreased, indicating a role for peroxynitrite formation as a mechanism of endothelial cell injury. In conclusion, the modulation of neutrophils causing superoxide production to dominate over nitrite release provides a reasonable explanation for endothelial cell dysfunction in preeclampsia.
Two Major QTLs and Several Others Relate to Factors of Metabolic Syndrome in the Family Blood Pressure Program
Authors: Kraja Aldi T. , Rao Dabeeru C. , Weder Alan B. , Cooper Richard , Curb J. David , Hanis Craig L. , Turner Stephen T. , de Andrade Mariza , Hsiung Chao Agnes , Quertermous Thomas , Zhu Xiaofeng , Province Michael A.
Published: September 2005

Genome-wide variance components linkage analysis was performed on 4 latent factors underlying metabolic syndrome derived from 10 risk factors. The latent factors represent obesity and insulin, blood pressure, lipids and insulin, and central obesity. The metabolic syndrome factor scores were derived in 4 ethnic groups recruited in 3 Networks of the Family Blood Pressure Program: GENOA (blacks, Hispanics, and whites), HyperGEN (blacks and whites), SAPPHIRe (Asians). Heritabilities of metabolic syndrome factors ranged from 66% for obesity and insulin to 11% for blood pressure factor. We observed higher heritabilities for obesity and insulin, and lipids and insulin, whereas those for blood pressure and central obesity were smaller. Linkage analysis detected two major quantitative trait loci. One of them linked to the obesity and insulin factor with a lod score of 3.94 (
P
=0.00001, marker GATA11A06, D18S53, 41.24 cM) at marker positions linkage (lod 4.71, at 46.84 cM at 1-cM-apart distances linkage), located on chromosome 18p11.21 in GENOA black. The other linked to the blood pressure factor with a lod score of 3.22 (
P
=0.000059, marker GATA49C09, D17S1290, 82 cM) at marker positions linkage (lod 3.56, at 84.63 cM for 1 cM apart distances linkage) located on chromosome 17q23.1 in Hispanics. These quantitative trait loci, together with 4 additional ones with lod scores >2.5, and 30 additional ones with lod score >1.7, offer hope for dissecting the genetic architecture of metabolic syndrome with beneficial implications for molecular diagnosis, prognosis, and in potential medical intervention.
Calcium Antagonists
Authors: Nathan Sandeep , Pepine Carl J. , Bakris George L.
Published: September 2005

Calcium antagonists comprise 2 main subclasses, dihydropyridines and nondihydropyridines, and have been studied extensively in hypertensive patients. Early meta-analyses suggested that short-acting calcium antagonists were associated with higher mortality rates resulting from cardiovascular events and other etiologies. Recent meta-analyses failed to show any substantive difference between long acting calcium antagonists and other antihypertensive drug classes with regard to cardiovascular outcomes in those with low to moderate cardiovascular risk or kidney disease progression among those with stage 2 or 3 nonproteinuric kidney diseases. The data from calcium antagonist trials are consistent in that they
decrease
stroke incidence but fail to protect against new-onset heart failure. In people with proteinuric kidney disease, that is >300 mg protein/gram creatinine, use of dihydropyridine calcium antagonists to lower blood pressure without the use of agents that block the renin angiotensin aldosterone system does not provide optimal slowing of nephropathy progression. This relates directly to lack of antiproteinuric effects with this subclass and not seen with nondihydropyridine agents that reduce proteinuria to a greater degree than dihydropyridines. Thus, calcium antagonists are safe and as efficacious as other antihypertensive agents to reduce cardiovascular risk. They should be avoided in people with systolic dysfunction but may be used for blood pressure lowering in people with preserved systolic function. Dihydropyridine calcium antagonists should only be used in conjunction with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in proteinuric kidney disease because they will not optimally slow kidney function loss in their absence.
Viral Persistence in the Myocardium Is Associated With Progressive Cardiac Dysfunction
Authors: Kühl Uwe , Pauschinger Matthias , Seeberg Bettina , Lassner Dirk , Noutsias Michel , Poller Wolfgang , Schultheiss Heinz-Peter
Published: September 2005

Background—

Cardiotropic viral infections have been suspected as one possible cause of myocarditis and dilated cardiomyopathy. Although adverse outcomes in dilated cardiomyopathy patients have been documented, the natural course of heart diseases caused by cardiotropic viruses is unknown.

Methods and Results—

Consecutive patients (n=172) with biopsy-proven viral infection in endomyocardial biopsies (EMBs) were followed up by reanalysis of EMBs and hemodynamic measurements after a median period of 6.8 months (range, 5.4 to 11.9). Nested polymerase chain reaction (PCR) and reverse transcription–PCR were performed to analyze the genomic sequences. Myocardial inflammation was assessed by histology and immunohistology. At baseline, 32.6% of EMBs in the study group contained enteroviral (EV) RNA, 8.1% adenovirus (ADV) DNA, 36.6% parvovirus B19 (PVB19) DNA, and 10.5% human herpesvirus type 6 (HHV6) DNA. In 12.2% of the samples, dual infection with PVB19 and HHV6 was present. Follow-up analysis of EMBs by PCR documented spontaneous clearance of viral genomes in 36.2% (55/151) of all patients with single infections. Virus-specific clearance rates were 50% for EV, 35.7% for ADV, 22.2% for PVB19, and 44.4% for HHV6. In patients with dual infection with PVB19
+
and HHV6
+
-, HHV6 was cleared in 42.8% (9/21), whereas PVB19 persisted in all 21 patients. Clearance of viral genomes was associated with a significant improvement in left ventricular ejection fraction (LVEF), improving from 50.2±19.1% to 58.1±15.9% (
P
<0.001). In contrast, LV function decreased in patients with persisting viral genomes (LVEF, 54.3±16.1% versus 51.4±16.1%,
P
<0.01).

Conclusions—

In this first biopsy-based analysis of the course of viral heart disease, we show that EV, ADV, PVB19, and HHV6 persistence detected in the myocardium of patients with LV dysfunction was associated with a progressive impairment of LVEF, whereas spontaneous viral elimination was associated with a significant improvement in LV function.
Kimbanguism: Its Present Christian Doctrine and the Problems Raised by it
Authors: Kayongo Léon Nguapitshi
Published: September 2005

Although the present publication does completely meet the requirements for an academic article, we have decided to publish it because of the insights it provides into the latest developments within the Kimbanguist Church in Congo. The author is a theologian who was Dean of the Kimbanguist Faculty of Theology in Lutendele near Kinshasa until mid 2003. He was deeply involved in the problems that arose in the beginning of the 21st century. He is also a person who is able to explain diligently the views of the different parties in the Kimbanguist Church. However, due to his own involvement in these developments the article has rather the character of a document written by a well-educated participant observer, who is very familiar with his subject, than that of a publication authored by a scholar who does his utmost to remain neutral.The document explains the theological, religious and contextual backdrops of the doctrine of the Trinity developed in the Kimbanguist Church, for in this church the persons of the Trinity are narrowly connected with the founder of the church and his family. Since 2001 these connections were even made more intense. Interestingly there are some Biblical reasons for it as well, but nonetheless the church seems to loose doctrinal familiarity with the other churches in the world through these new evolutions.
Why Become a Rainbow Church?
Authors: Calvert Robert
Published: September 2005

Across the cities of Europe, there are new and growing Christian communities with leadership originating from Asia, Africa and Latin America. In recent years, the formation of SKIN (Samen Kerk in Nederland — Together Church in the Netherlands) and the publication of a book entitled Geboren in Sion (Born in Sion) have contributed to our understanding. However, it remains a major challenge for the indigenous churches to relate to their life and spirituality. Can we learn from Biblical models of heterogeneous and multicultural Christian communities in the New Testament? Different aspects of the identity and contrasting types of so-called migrant churches are explored in this paper which was first presented to the migrant study group at the Landelijke Diensten Centrum (National Service Centre) of the Protestantse Kerken in Nederland (Protestant Churches in the Netherlands) in Utrecht on November 15, 2004. Some examples have been cited from the city of Rotterdam and questions raised in order to how to recognize and receive their spiritual gift in the Netherlands.
Religion for Another Possible World
Authors: Balasuriya Tissa
Published: September 2005

Figures derived from statistics show that large numbers of inhabitants of Europe have migrated all over the world in the past. Nowadays they still dominate economic and technological developments causing injustice in many countries, mainly outside Europe. As a result the economic system of the world is fundamentally unjust. Moreover the technological development supports the dominating powers at the cost of the poor and the oppressed. In the meantime a religious awakening is taking place. Unfortunately this religious renaissance tends to promote violence in many parts of the world. Therefore another religion is needed for another possible world. The second part of the article delineates the outlines of that other religion, which the main world religions seek for mutual contact and disclose the dangerous relationship between religion and power in many areas hoping to attain real conversion: choosing for the humanist core each world religion possesses.
Gendered Reactions
Authors: Banwart Mary Christine , Bystrom Dianne G.
Published: September 2005

Considering the 2004 campaign’s attention to the gender gap in voting between women and men and efforts to turn out the youth vote, this study examines the reactions of 301 female and male young voters to televised political advertisements aired on behalf of the two major party presidential candidates. Specifically, the authors compare how women and men rate each candidate’s overall favorability and individual character traits as well as indicate their vote intention for George W. Bush or John Kerry. The authors find that the gender gap in vote intention is similar to, but larger than, the actual gender gap in voting in 2004, both overall and for young voters. However, assessments of candidate favorability follow the gender gap only for the Democratic candidate.
Political Advertising in the 2004 Election
Authors: Kaid Lynda Lee , Postelnicu Monica
Published: September 2005

Although television advertising remained a dominant form of communication in the 2004 presidential election, the Internet reached new levels of campaign importance, providing voters with information from candidates, the media, and independent sources. Internet sites not only provided online viewing of traditional television advertising but also provided voters with the opportunity to seek out additional information about television ads viewed on the Web. Drawing on theory and research related to channel variables, this study compared the reactions of young voters who experienced candidate advertising on television or on the Web. Results indicate that the channel really does make a difference. John Kerry’s ads were more successful in raising his image and learning scores when viewed on the Web with access to additional information sources. However, television viewing reduced feelings of political cynicism and alienation for young voters.
Political Affiliation and Presidential Debates
Authors: Jarman Jeffrey W.
Published: September 2005

This study reports the reactions by registered voters to the second presidential debate in 2004. Respondents used a continuous response system that provided feedback in 1-second intervals. These data were compared to a transcript of the debate to identify the strongest and weakest arguments made by candidates both for their own party and for the opposition party. Results suggest that political affiliation strongly influences audience reaction in two ways: (a) Republicans always rated Bush’s comments higher than Democrats, whereas Democrats always rated Kerry’s comments higher than Republicans; and (b) Republicans believed that Bush won the debate, whereas Democrats believed that Kerry won the debate. This research provides new support for the conclusion that debates tend to reinforce the preexisting positions of the audience but offers a warning that the amount of learning that takes place could be limited.
On Building a Unified System of Accreditation in Teacher Education
Authors: Murray Frank B.
Published: September 2005

As of September 2003, there are officially two recognized accreditors for teacher education programs in the United States, each with a distinctly different approach to accreditation. The Teacher Education Accreditation Council (TEAC), the more recently developed accreditor, has been criticized for promoting “accreditation shopping,” lacking standards, illegitimacy, insensitivity to diversity, and divisiveness. TEAC’s position on each of these issues is explicated along with an analysis of other issues that in contrast to the foregoing, are genuine and truly distinguish the two accreditors. An exploration of the differences and similarities between TEAC and the National Council for Accreditation of Teacher Education suggests the ingredients of a unified accreditation system.
Verbal Ability and Teacher Effectiveness
Authors: Andrew Michael D. , Cobb Casey D. , Giampietro Peter J.
Published: September 2005

Critics of traditional teacher education programs have suggested that verbal ability along with subject knowledge is sufficient for measuring good teaching. A small group of research studies is called upon to support this contention. This article reviews these studies, analyzes the role of verbal ability in teaching, and presents research examining the relationship of teachers’ verbal ability and teacher effectiveness. Research results indicate that for acceptable, good, very good, and outstanding teachers, there is no significant correlation between verbal scores and expert assessment of teacher effectiveness. However, weaker teachers have lower average verbal scores. This research and logical analysis suggest that educators should take verbal ability into account, but due to the wide range of scores among good to excellent teachers, it is inadvisable to use single measures of verbal ability to measure or predict teacher effectiveness. The authors provide an alternative system for teacher selection.
Knowledge Interactions in Teacher-Scientist Partnerships
Authors: Nelson Tamara Holmlund
Published: September 2005

The purpose of this study was to understand how teachers and graduate-level scientists negotiated differing knowledge bases to work together to improve science teaching and learning. Partners’ coparticipation in and dialogue about pedagogical decisions and actions were analyzed. Three theoretical representations of dialogic interactions emerged from this analysis: knowledge negotiation, consultation, and rejection. Knowledge negotiation was a sustained inquiry stance involving intentional actions to understand each other’s knowledge representations. This was theorized as having the most potential for transformation of the cultural resources associated with science education. Only one of the nine partnerships in the study was characterized by knowledge negotiation. To explain this, the extensive support for university partners in creating a dialogic community is contrasted with the lack of support for participating teachers. The existence of power differentials between partners and the relevance of this to knowledge consultation are also discussed.
Qualitative Relational Career Assessment: A Constructivist Paradigm
Authors: Schultheiss Donna E. Palladino
Published: September 2005

Consistent with calls for postmodern and constructivist approaches to career counseling and assessment, a systematic review of qualitative approaches to the assessment of work and relationships is timely. Situated within a constructivist paradigm, a conceptual rationale for the qualitative assessment of relational influences within the career domain is presented, together with a comprehensive review of the state of the art of current qualitative relational career assessment practices. This review is followed by a recommendation to move the field forward toward a more contextualized view of work embedded within the relational domains of life.
Qualitative Research in Career Development: Exploring the Center and Margins of Discourse About Careers and Working
Authors: Blustein David L. , Kenna Alexandra C. , Murphy Kerri A. , DeVoy Julia E. , DeWine David B.
Published: September 2005

This article explores the contributions of qualitative research to the study of career development and the psychology of working. Epistemological perspectives (logical positivism, postpositivism, and social constructionism) are discussed as they relate to historical context, career theories, and the various methods used within qualitative research. Prevailing qualitative methods within career development and the psychology of working, such as consensual qualitative research, grounded theory, and narrative analysis, are reviewed. The article examines exemplary lines of qualitative research on women’s achievements, school-to-work transitions, work and relationships, and the constructions of school and work. Finally, the article concludes with an example of an assessment tool that is derived from research on constructions of work and school.
Resilience: A Protector From Depression
Authors: Edward Karen-leigh
Published: September 2005

Personality type and resilient behaviors provide protection from the experience of depression, and resilience can increase the risk of not being depressed. Psychiatric–mental health nurses are well positioned to facilitate the development of resilience qualities in people who are depressed. Clinical strategies, which could be undertaken by the psychiatric–mental health nurse, include early intervention, promoting a positive social and familial climate, promoting self-esteem and support building, social and life skills/vocational education, and linking and brokering clients into extracurricular activities.
Temporal Patterning of Agitation and Stressors Associated With Agitation: Case Profiles to Illustrate the Progressively Lowered Stress Threshold Model
Authors: Gerdner Linda A. , Buckwalter Kathleen C. , Hall Geri Richards
Published: September 2005

BACKGROUND: Stressors in persons with dementia (PWD) are often unrecognized until serving to trigger challenging behaviors, such as agitation. OBJECTIVE: The purpose of this study was to examine temporal patterning of stressors associated with agitation in PWD as postulated in the progressively lowered stress threshold (PLST) model. STUDY DESIGN: Baseline data of agitation from an intervention study of 39 cognitively impaired elders residing in a long-term care facility were analyzed. A modified Cohen-Mansfield Agitation Inventory was used during a 3-week period to document the frequency of agitation twice weekly for an hour during estimated “peak levels of agitation.” Anecdotal notes documented stressors. RESULTS: Case profiles were developed to illustrate factors identified in the PLST model that may contribute to stress and cause agitation. CONCLUSIONS: Findings suggest that temporal patterning of agitated behaviors in PWD may be predictable based on the PLST model. Recognizing early signs of agitation and its underlying meaning can facilitate timely and appropriate intervention by psychiatric nurses.
Distress Responses and Self-Care Behaviors in Dementia Family Caregivers With High and Low Depressed Mood
Authors: Yueh-Feng Lu Yvonne , Austrom Mary Guerriero
Published: September 2005

BACKGROUND: Most caregiving intervention studies have focused on reducing caregiver depression. Little is known about how caregivers manage their own symptoms, particularly caregivers with high depressed mood. OBJECTIVES: To compare caregiving stress, health status, physical function, symptom presence and severity, and self-care behaviors in family caregivers with high and low depressed mood. STUDY DESIGN: This study used a cross-sectional design. RESULTS: Caregivers with high depressed mood reported higher levels of caregiving stress, experienced more symptoms and more symptom severity, and had more physical performance difficulty than those caregivers with low depressed mood. However, they did not report a higher rate of asking for professional help per symptom. CONCLUSIONS: There is a need for developing outreach programs and coordinating information to encourage caregivers to address their own symptoms, identify services available in the community, and learn how to access them.
Effects of Cervical Rotation on Hemodynamics in Vertebral Arteries
Authors: Ozdemir Huseyin , Cihangiroglu Mutlu , Berilgen Said , Bulut Serpil
Published: September 2005

The purpose of this study was to assess the effects of cervical rotations on flow velocity and volumes of vertebral arteries in healthy individuals and patients with cervical spondylosis and vertebrobasilar insufficiency. Twenty-eight patients with degenerative changes in the cervical spine (group 1), 24 patients with clinically proven vertebrobasilar insufficiency (group 2), and 20 healthy individuals (group 3) were evaluated. Significant difference was found in flow velocities of both vertebral arteries during neutral, 30-degree, 60-degree, and maximum rotations between groups 1 to 3 and groups 2 to 3. No significant difference was observed in flow velocities and volumes of the vertebral artery between groups 1 and 2. This occurrence might be explained by the fact that both groups have been affected not only by atherosclerotic changes but also by external pressure due to degenerative changes in the cervical spine.
First-Trimester Ectopia Cordis in a Twin Gestation, Using 3D Surface Rendering and Reconstruction
Authors: Hill Donald S.
Published: September 2005

Ectopia cordis is a very rare and impressive congenital abnormality. This case study demonstrates an 8-week, 5-day twin gestation with one embryo affected and the other normal. The abnormal fetus spontaneously expired at 11 weeks, 5 days gestation. The surviving twin remains alive and well at 18 weeks gestation. Because of the ongoing normal pregnancy, pathologic confirmation is unlikely.
Schistosomiasis
Authors: Stone Chris
Published: September 2005

Schistosomiasis is a disease that is relatively rare in the United States but has become an endemic in more than 74 countries. This disease has infected some 200 million people worldwide, particularly in developing countries. The disease is caused by parasitic worms, or flukes, which reside in contaminated or poorly sanitized fresh water. The most common effects of the disease are urinary tract and abdominal/intestinal disorders. Sonography has become an invaluable tool in detecting the clinical presentation of schistosomiasis, although lab studies of fecal and urine contents are the required to confirm infection. Although there is no current vaccine available for schistosomiasis, advances in drugs such as praziquantel, oxamniquine, and metrifonate have led to highly effective treatment. These drugs have led to a substantial reduction in morbidity in many areas. Mortality rates have also declined, but when present, it is usually due to intestinal bleeding or bladder cancer.
Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells
Authors: Wei Xiu M , Kim Henry S , Kumar Rakesh K , Heywood Gavin J , Hunt John E , McNeil H Patrick , Thomas Paul S
Published: September 2005

Exhaled nitric oxide (eNO) is decreased by cigarette smoking. The hypothesis that oxides of nitrogen (NOX) in cigarette smoke solution (CSS) may exert a negative feedback mechanism upon NO release from epithelial (AEC, A549, and NHTBE) and basophilic cells (RBL-2H3) was tested in vitro. CSS inhibited both NO production and degranulation (measured as release of beta-hexosaminidase) in a dose-dependent manner from RBL-2H3 cells. Inhibition of NO production by CSS in AEC, A549, and NHTBE cells was also dose-dependent. In addition, CSS decreased expression of NOS mRNA and protein expression. The addition of NO inhibitors and scavengers did not, however, reverse the effects of CSS, nor did a NO donor (SNP) or nicotine mimic CSS. N-acetyl-cysteine, partially reversed the inhibition of beta-hexosaminidase release suggesting CSS may act via oxidative free radicals. Thus, some of the inhibitory effects of CSS appear to be via oxidative free radicals rather than a NOX -related negative feedback.
ProbeMaker: an extensible framework for design of sets of oligonucleotide probes
Authors: Stenberg Johan , Nilsson Mats , Landegren Ulf
Published: September 2005

Background

Procedures for genetic analyses based on oligonucleotide probes are powerful tools that can allow highly parallel investigations of genetic material. Such procedures require the design of large sets of probes using application-specific design constraints.

Results

ProbeMaker is a software framework for computer-assisted design and analysis of sets of oligonucleotide probe sequences. The tool assists in the design of probes for sets of target sequences, incorporating sequence motifs for purposes such as amplification, visualization, or identification. An extension system allows the framework to be equipped with application-specific components for evaluation of probe sequences, and provides the possibility to include support for importing sequence data from a variety of file formats.

Conclusion

ProbeMaker is a suitable tool for many different oligonucleotide design and analysis tasks, including the design of probe sets for various types of parallel genetic analyses, experimental validation of design parameters, and in silico testing of probe sequence evaluation algorithms.
Diversity in domain architectures of Ser/Thr kinases and their homologues in prokaryotes
Authors: Krupa A , Srinivasan N
Published: September 2005

Background

Ser/Thr/Tyr kinases (STYKs) commonly found in eukaryotes have been recently reported in many bacterial species. Recent studies elucidating their cellular functions have established their roles in bacterial growth and development. However functions of a large number of bacterial STYKs still remain elusive. The organisation of domains in a large dataset of bacterial STYKs has been investigated here in order to recognise variety in domain combinations which determine functions of bacterial STYKs.

Results

Using sensitive sequence and profile search methods, domain organisation of over 600 STYKs from 125 prokaryotic genomes have been examined. Kinase catalytic domains of STYKs tethered to a wide range of enzymatic domains such as phosphatases, HSP70, peptidyl prolyl isomerases, pectin esterases and glycoproteases have been identified. Such distinct preferences for domain combinations are not known to be present in either the Histidine kinase or the eukaryotic STYK families. Domain organisation of STYKs specific to certain groups of bacteria has also been noted in the current anlaysis. For example, Hydrophobin like domains in Mycobacterial STYK and penicillin binding domains in few STYKs of Gram-positive organisms and FHA domains in cyanobacterial STYKs. Homologues of characterised substrates of prokaryotic STYKs have also been identified.

Conclusion

The domains and domain architectures of most of the bacterial STYKs identified are very different from the known domain organisation in STYKs of eukaryotes. This observation highlights distinct biological roles of bacterial STYKs compared to eukaryotic STYKs. Bacterial STYKs reveal high diversity in domain organisation. Some of the modular organisations conserved across diverse bacterial species suggests their central role in bacterial physiology. Unique domain architectures of few other groups of STYKs reveal recruitment of functions specific to the species.
Characterization of the global profile of genes expressed in cervical epithelium by Serial Analysis of Gene Expression (SAGE)
Authors: Pérez-Plasencia Carlos , Riggins Gregory , Vázquez-Ortiz Guelaguetza , Moreno José , Arreola Hugo , Hidalgo Alfredo , Piña-Sanchez Patricia , Salcedo Mauricio
Published: September 2005

Background

Serial Analysis of Gene Expression (SAGE) is a new technique that allows a detailed and profound quantitative and qualitative knowledge of gene expression profile, without previous knowledge of sequence of analyzed genes. We carried out a modification of SAGE methodology (microSAGE), useful for the analysis of limited quantities of tissue samples, on normal human cervical tissue obtained from a donor without histopathological lesions. Cervical epithelium is constituted mainly by cervical keratinocytes which are the targets of human papilloma virus (HPV), where persistent HPV infection of cervical epithelium is associated with an increase risk for developing cervical carcinomas (CC).

Results

We report here a transcriptome analysis of cervical tissue by SAGE, derived from 30,418 sequenced tags that provide a wealth of information about the gene products involved in normal cervical epithelium physiology, as well as genes not previously found in uterine cervix tissue involved in the process of epidermal differentiation.

Conclusion

This first comprehensive and profound analysis of uterine cervix transcriptome, should be useful for the identification of genes involved in normal cervix uterine function, and candidate genes associated with cervical carcinoma.
Bone mineral density and cytokine levels during interferon therapy in children with chronic hepatitis B: does interferon therapy prevent from osteoporosis?
Authors: Gur Ali , Dikici Bünyamin , Nas Kemal , Bosnak Mehmet , Haspolat Kenan , Sarac Aysegul Jale
Published: September 2005

Background

Our aim was to determinate bone mineral density (BMD), levels of biochemical markers and cytokines in children with chronic hepatitis B treated with interferon (IFN)-alpha and to investigate effect of IFN-alpha therapy on these variables. To the best of our knowledge, this is first study carried out about BMD and cytokine levels in pediatric patients with chronic hepatitis B treated with IFN-alpha.

Methods

BMD, levels of parathyroid hormone (PTH), osteocalcin, C-terminal cross-linking telopeptide of type I collagen (CTX), calcium, alkaline phosphates (ALP), cytokines as TNF-alpha, interleukin (IL)-1β, IL-2r, IL-6, and IL-8 were studied in 54 children with chronic hepatitis B (4–15 years old) treated with interferon alone (n = 19) or in combination with lamivudine (n = 35) for six months and as controls in 50 age-matched healthy children.

Results

There was no significant difference in respect to serum IL-1β, TNF-α and osteocalcin levels while serum IL-2r (p = 0.002), IL-6 (p = 0.001), IL-8 (p = 0.013), PTH (p = 0.029), and CTX (p = 0.021) levels were higher in children with chronic hepatitis B than in healthy controls. BMD of femur neck (p = 0.012) and trochanter (p = 0.046) in patients were higher than in healthy controls. There was a statistically significant correlation between serum IL-1β and osteocalcin (r = -0.355, p < 0.01); between serum IL-8 and CTX levels (r = 0.372, p = 0.01), and ALP (r = 0.361, p = 0.01); between serum ALP and femur neck BMD (r = 0.303, p = 0.05), and trochanter BMD (r = 0.365, p = 0.01); between spine BMD and IL-2R (r = -0.330, p < 0.05).

Conclusion

In conclusion, our study suggest that BMD of femur, serum IL-2r, IL-6, IL-8, PTH, and CTX levels were higher in children with chronic hepatitis B treated with IFN-alpha alone or combination with lamivudine than in healthy children. High femur BMD measurements found in patients may suggest that IFN-alpha therapy in children with chronic hepatitis B could contribute indirectly to prevent from hip osteoporosis. Additionally, further investigations on effects of IFN-alpha for bone structure in children should be performed in the future.
Oral ulcer as an exclusive sign of gastric cancer: report of a rare case
Authors: Colombo Piergiuseppe , Tondulli Luca , Masci Giovanna , Muzza Andrea , Rimassa Lorenza , Petrella Duccio , Santoro Armando
Published: September 2005

Background

The oral cavity is a rare but occasional target for metastases, which may masquerade as various benign and inflammatory lesions, and sometimes also be asymptomatic. Oral metastatic lesions have been described in various cancers, particularly lung, breast and kidney carcinoma.

Case presentation

We here describe an uncommon case of a hard palate mucosa and gingival metastasis from gastric carcinoma that was originally diagnosed as a periodontal disease.

Histopathological examination of a biopsy of the lesion revealed a signet-ring cell carcinoma, and a subsequent biopsy of an ulcerated stomach lesion showed a poorly differentiated gastric carcinoma. The patient underwent gastric resection but died of heart failure on the tenth postoperative day; a post-mortem examination revealed a residual bilateral ovarian infiltration by gastric carcinoma (Krukenberg's tumor).

Conclusion

An occult carcinoma of the stomach may rarely metastasise to the oral cavity even as a first and exclusive manifestation; it is important to bear this possibility in mind because such conditions may mimic a benign disease.
Investigation of the expression of the EphB4 receptor tyrosine kinase in prostate carcinoma
Authors: Lee Yen-Ching , Perren Janeanne R , Douglas Evelyn L , Raynor Michael P , Bartley Maria A , Bardy Peter G , Stephenson Sally-Anne
Published: September 2005

Background

The EphB4 receptor tyrosine kinase has been reported as increased in tumours originating from several different tissues and its expression in a prostate cancer xenograft model has been reported.

Methods

RT-PCR, western blotting and immunohistochemical techniques were used to examine EphB4 expression and protein levels in human prostate cancer cell lines LNCaP, DU145 and PC3. Immunohistochemistry was also used to examine localisation of EphB4 in tissue samples from 15 patients with prostate carcinomas.

Results

All three prostate cancer cell lines expressed the EphB4 gene and protein. EphB4 immunoreactivity in vivo was significantly greater in human prostate cancers as compared with matched normal prostate epithelium and there appeared to be a trend towards increased expression with higher grade disease.

Conclusion

EphB4 is expressed in prostate cancer cell lines with increased expression in human prostate cancers when compared with matched normal tissue. EphB4 may therefore be a useful anti-prostate cancer target.
How to promote, improve and test adherence to scientific evidence in clinical practice
Authors: Caminiti Caterina , Scoditti Umberto , Diodati Francesca , Passalacqua Rodolfo
Published: September 2005

Background

Negative variation in the management of patients with the same clinical condition is frequent, and affects quality of care. Recent studies indicate that single interventions are not an effective solution. We aim to demonstrate that a multifaceted strategy can favor the introduction of research into practice, and to assess its long-term effects on a set of common medical conditions exhibiting significant negative variation at our institution.

Methods

The strategy, devised and agreed upon by a multidisciplinary group, was first applied to one relevant medical condition – cerebral ischemic stroke. To test its effectiveness a quasi-experimental study was conducted, comparing an intervention group with historical controls. After validation the strategy was extended to other pathologies, and its long-term effect measured using evidence-based quality indicators. Adherence to each indicator was determined prospectively on a six-month basis for a period of at least two consecutive years. Measures are expressed as proportions with 95% confidence intervals.

Results

Validation findings demonstrated that the strategy improved compliance with scientific evidence: the percentage of patients who received a CT scan within 24 hours of hospital presentation rose from 56% to 75%, (χ2 = 7.43 p < 0.01); admissions to selected wards increased from 45% to 64%, (χ2 = 7.81 p < 0.01); the number of physical medicine visits within 24 hours of the request grew from 59% to 91% (χ2 = 14,40 p < 0.001). Over a four-year period the program was gradually applied to 14 medical conditions. Except for 3 cases, compliance with the pathway, i.e. number of eligible patients for whom data on the care process is collected, was above the minimum requirement of 75%. Indicator adherence generally exhibited a positive trend, though variability was observed both among different conditions and between different semesters for the same pathology.

Conclusion

According to our experience, incorporation of research into practice can be favored by systematically applying a shared, multifaceted strategy, involving multidisciplinary teams supported by central coordination. Institutions should device a tailor-made approach, should train personnel on implementation strategies, and create cultural acceptance of change. Just like for experimental trials, human and economic resources should be allocated within health care services to allow the achievement of this objective.
Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study
Authors: Clayton Richard H , Taggart Peter
Published: September 2005

Background

Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood.

Methods

We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution.

Results

Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms).

Conclusion

Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve.
5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia
Authors: Ayasolla Kamesh R , Giri Shailendra , Singh Avtar K , Singh Inderjit
Published: September 2005

Background

Alzheimer's disease (AD) pathology shows characteristic 'plaques' rich in amyloid beta (Aβ) peptide deposits. Inflammatory process-related proteins such as pro-inflammatory cytokines have been detected in AD brain suggesting that an inflammatory immune reaction also plays a role in the pathogenesis of AD. Glial cells in culture respond to LPS and Aβ stimuli by upregulating the expression of cytokines TNF-α, IL-1β, and IL-6, and also the expression of proinflammatory genes iNOS and COX-2. We have earlier reported that LPS/Aβ stimulation-induced ceramide and ROS generation leads to iNOS expression and nitric oxide production in glial cells. The present study was undertaken to investigate the neuroprotective function of AICAR (a potent activator of AMP-activated protein kinase) in blocking the pro-oxidant/proinflammatory responses induced in primary glial cultures treated with LPS and Aβ peptide.

Methods

To test the anti-inflammatory/anti-oxidant functions of AICAR, we tested its inhibitory potential in blocking the expression of pro-inflammatory cytokines and iNOS, expression of COX-2, generation of ROS, and associated signaling following treatment of glial cells with LPS and Aβ peptide. We also investigated the neuroprotective effects of AICAR against the effects of cytokines and inflammatory mediators (released by the glia), in blocking neurite outgrowth inhibition, and in nerve growth factor-(NGF) induced neurite extension by PC-12 cells.

Results

AICAR blocked LPS/Aβ-induced inflammatory processes by blocking the expression of proinflammatory cytokine, iNOS, COX-2 and MnSOD genes, and by inhibition of ROS generation and depletion of glutathione in astroglial cells. AICAR also inhibited down-stream signaling leading to the regulation of transcriptional factors such as NFκB and C/EBP which are critical for the expression of iNOS, COX-2, MnSOD and cytokines (TNF-α/IL-1β and IL-6). AICAR promoted NGF-induced neurite growth and reduced neurite outgrowth inhibition in PC-12 cells treated with astroglial conditioned medium.

Conclusion

The observed anti-inflammatory/anti-oxidant and neuroprotective functions of AICAR suggest it as a viable candidate for use in treatment of Alzheimer's disease.