bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Valosin-Containing Protein in Colorectal Carcinomas as a Predictor for Disease Recurrence and Prognosis
Authors: Yamamoto Shinji , Tomita Yasuhiko , Hoshida Yoshihiko , Sakon Masato , Kameyama Masao , Imaoka Shingi , Sekimoto Mitsugu , Nakamori Shoji , Monden Morito , Aozasa Katsuyuki
Published: September 2005

Purpose: Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-κB signaling pathway. The present study was designed to investigate the prognostic significance of VCP expression in colorectal adenocarcinoma.

Experimental Design: We analyzed VCP expression immunohistochemically in 129 patients with colorectal carcinoma ages 35–84 years. The staining intensity of tumor cells was categorized as either weaker-to-equal (low VCP expression) or stronger (high expression) than that in noncancerous colonic mucosa. We also analyzed 8 colorectal adenomas and 10 metastatic foci.

Results: Low VCP expression was noted in 41 (31.8%) cases and high expression in 88 (68.2%) cases. A low level of VCP expression was noted in all adenomas, whereas a high level was seen in all metastatic tumors. A significant difference was observed in depth of invasion (T1–2 versus T3–4, P < 0.05), presence or absence of venous invasion (P < 0.05), and tumor stage (I and II versus III and IV; P < 0.05) between adenocarcinomas with low and high VCP expression. Patients with high VCP-expressing tumors had a higher recurrence rate (P < 0.001) and poorer disease-free and overall survival (P < 0.01 and P < 0.05, respectively) compared with the low expression group. Multivariate analysis revealed VCP expression level to be an independent prognosticator for both disease-free and overall survival. VCP level was an indicator of disease-free survival in both stage II and III (pathological Tumor-Node-Metastasis classification, P < 0.05 and <0.01, respectively).

Conclusions: A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.
E1A Specifically Enhances Sensitivity to Topoisomerase IIα Targeting Anticancer Drug by Up-Regulating the Promoter Activity
Authors: Zhou Zhichao , Guan Hui , Kleinerman Eugenie S.
Published: September 2005

DNA topoisomerases I and II (topo I and II) are nuclear enzymes involved in cellular replication and are targets for several anticancer drugs. We showed previously that E1A gene transfer enhanced the sensitivity of Ewing's sarcoma cells to the topo IIα targeting agents etoposide and Adriamycin in vitro and in vivo. To determine whether this effect was specific for topo IIα, we investigated the effect of E1A gene transfer on cell sensitivity to agents that target topo I and IIβ. Transfecting TC71 human Ewing's sarcoma cells with an adenoviral vector containing the E1A gene enhanced their sensitivity to the topo IIα targeting agents etoposide (16-fold) and Adriamycin (8-fold). By contrast, E1A gene transfer did not affect cellular sensitivity to either amsacrine or camptothecin. Western blot analysis indicated that topo IIα protein levels increased 3.1-fold after E1A gene transfer, but topo I and IIβ protein levels did not change. A plasmid containing topo IIα gene promoter with luciferase reporter gene was constructed to determine the effects of E1A gene transfer on the activity of the topo IIα promoter. E1A increased the activity of the topo IIα gene promoter by 3.5-fold relative to that of cells transfected with Ad-β-gal. These results suggest that elevated topo IIα protein levels and enhanced sensitivity to topo IIα targeting agents were secondary to a direct effect of E1A on the topo IIα promoter. Combining E1A gene therapy with topo IIα targeting anticancer drugs may therefore have therapeutic benefit by increasing tumor cell sensitivity.
Sphingosine-1-Phosphate Lyase Regulates Sensitivity of Human Cells to Select Chemotherapy Drugs in a p38-Dependent Manner
Authors: Min Junxia , Van Veldhoven Paul P. , Zhang Lei , Hanigan Marie H. , Alexander Hannah , Alexander Stephen
Published: September 2005

Resistance to cisplatin is a common problem that limits its usefulness in cancer therapy. Molecular genetic studies in the model organism Dictyostelium discoideum have established that modulation of sphingosine kinase or sphingosine-1-phosphate (S-1-P) lyase, by disruption or overexpression, results in altered cellular sensitivity to this widely used drug. Parallel changes in sensitivity were observed for the related compound carboplatin but not for other chemotherapy drugs tested. Sensitivity to cisplatin could also be potentiated pharmacologically with dimethylsphingosine, a sphingosine kinase inhibitor. We now have validated these studies in cultured human cell lines. HEK293 or A549 lung cancer cells expressing human S-1-P lyase (hSPL) show an increase in sensitivity to cisplatin and carboplatin as predicted from the earlier model studies. The hSPL-overexpressing cells were also more sensitive to doxorubicin but not to vincristine or chlorambucil. Studies using inhibitors to specific mitogen-activated protein kinases (MAPK) show that the increased cisplatin sensitivity in the hSPL-overexpressing cells is mediated by p38 and to a lesser extent by c-Jun NH2-terminal kinase MAPKs. p38 is not involved in vincristine or chlorambucil cytotoxicity. Measurements of MAPK phosphorylation and enzyme activity as well as small interfering RNA inhibition studies show that the response to the drug is accompanied by up-regulation of p38 and c-Jun NH2-terminal kinase and the lack of extracellular signal-regulated kinase up-regulation. These studies confirm an earlier model proposing a mechanism for the drug specificity observed in the studies with D. discoideum and support the idea that the sphingosine kinases and S-1-P lyase are potential targets for improving the efficacy of cisplatin therapy for human tumors.
Low-Renin Hypertension With Relative Aldosterone Excess Is Associated With Impaired NO-Mediated Vasodilation
Authors: Duffy Stephen J. , Biegelsen Elizabeth S. , Eberhardt Robert T. , Kahn David F. , Kingwell Bronwyn A. , Vita Joseph A.
Published: September 2005

Recent studies suggest that hypertension associated with low renin status and hyperaldosteronism is associated with increased risk for end-organ damage and cardiovascular events compared with other forms of hypertension. Additionally, experimental studies have demonstrated impaired nitric oxide-mediated bioactivity in these states. To investigate the relation between renin/aldosterone status and resistance vessel function, we examined plasma renin activity, serum aldosterone level, and forearm blood flow responses to the endothelium-dependent vasodilator methacholine and the endothelium-independent vasodilators sodium nitroprusside and verapamil using venous occlusion plethysmography in 130 volunteers (43 hypertensive, 87 normotensive). Low renin status was associated with impaired responses to methacholine and nitroprusside in patients with hypertension. Peak methacholine response was 8.7±5.6 mL/min per dL in the lowest renin quartile (0.1 to 0.3 ng/mL per hour) versus 14.3±7.3 mL/min per dL in the highest 3 renin quartiles combined (0.4 to 4.6 ng/mL per hour;
P
<0.001). Peak nitroprusside response was 5.6±2.3 mL/min per dL in the lowest renin quartile versus 13.3±4.1 mL/min per dL in the highest 3 renin quartiles combined (
P
<0.001). Blood pressure and other clinical characteristics were similar in all 4 quartiles. Vasodilator responses to verapamil did not relate to renin activity. Methacholine and nitroprusside responses did not relate to renin status in normotensive controls (
P
=0.34). Importantly, hypertensive patients with a high aldosterone/renin ratio also had impaired responses to methacholine. This study demonstrates that low-renin hypertension is associated with marked impairment of nitric oxide-mediated vasodilation of resistance vessels in the forearm vasculature of humans. This impairment could contribute to adverse outcomes in patients with low-renin hypertension and relative aldosterone excess.
Pathways of Renal Fibrosis and Modulation of Matrix Turnover in Experimental Hypercholesterolemia
Authors: Chade Alejandro R. , Mushin Oren P. , Zhu Xiangyang , Rodriguez-Porcel Martin , Grande Joseph P. , Textor Stephen C. , Lerman Amir , Lerman Lilach O.
Published: September 2005

Dyslipidemia often accompanies and accelerates renal disease, partly by promoting fibrosis. However, the mechanisms mediating this effect are unclear. We hypothesized that hypercholesterolemia modulates several interlinked pathways that promote deposition and blunt degradation of extracellular matrix, and that these could be manipulated by reversal of hypercholesterolemia. Fourteen pigs were fed a 16-week 2% high-cholesterol diet (HC-HC; n=7) or normal diet (n=7), whereas in 7 others, a 10-week HC was followed by a 6-week normal diet (HC-N). Renal endothelial function was assessed in vivo with electron-beam computed tomography, and renal tissue was then studied ex vivo using Western blot, real-time quantitative polymerase chain reaction, gelatin zymography, and immunostaining. HC-HC kidneys showed endothelial dysfunction, accompanied by increased intrarenal oxidative stress, inflammation, activation of the endothelin and transforming-growth factor-β systems, and decreased matrix metalloproteinase expression and activity. Accordingly, HC-HC kidneys showed increased collagen IV expression and fibrosis. A lipid-lowering dietary intervention reversed most of these changes. In conclusion, this study indicates that renal fibrosis in early atherosclerosis is a result of a simultaneous increase in extracellular matrix deposition and blunted matrix metalloproteinase–mediated degradation, overall promoting perivascular and tubulointerstitial fibrosis. Notably, many of these pathways may be reversible in hypercholesterolemia, and crucial targets could potentially be identified for early interventions to preserve the kidney.
Rat Strain Effects of AT
1
Receptor Activation on D
1
Dopamine Receptors in Immortalized Renal Proximal Tubule Cells
Authors: Zeng Chunyu , Wang Zheng , Hopfer Ulrich , Asico Laureano D. , Eisner Gilbert M. , Felder Robin A. , Jose Pedro A.
Published: September 2005

The dopaminergic and renin-angiotensin systems regulate blood pressure, in part, by affecting sodium transport in renal proximal tubules (RPTs). We have reported that activation of a D
1
-like receptor decreases AT
1
receptor expression in the mouse kidney and in immortalized RPT cells from Wistar-Kyoto (WKY) rats. The current studies were designed to test the hypothesis that activation of the AT
1
receptor can also regulate the D
1
receptor in RPT cells, and this regulation is aberrant in spontaneously hypertensive rats (SHRs). Long-term (24 hours) stimulation of RPT cells with angiotensin II, via AT
1
receptors increased total cellular D
1
receptor protein in a time- and concentration-dependent manner in WKY but not in SHR cells. Short-term stimulation (15 minutes) with angiotensin II did not affect total cellular D
1
receptor protein in either rat strain. However, in the short-term experiments, angiotensin II decreased cell surface membrane D
1
receptor protein in WKY but not in SHR cells. D
1
and AT
1
receptors colocalized (confocal microscopy) and their coimmunoprecipitation was greater in WKY than in SHRs. However, AT
1
/D
1
receptor coimmunoprecipitation was decreased by angiotensin II (10
−8
M/24 hours) to a similar extent in WKY (−22±8%) and SHRs (−22±12%). In summary, these studies show that AT
1
and D
1
receptors interact differently in RPT cells from WKY and SHRs. It is possible that an angiotensin II-mediated increase in D
1
receptors and dissociation of AT
1
from D
1
receptors serve to counter regulate the long-term action of angiotensin II in WKY rats; different effects are seen in SHRs.
Remodeling of Blood Vessels
Authors: Pries Axel R. , Reglin Bettina , Secomb Timothy W.
Published: September 2005

Vascular functions, including tissue perfusion and peripheral resistance, reflect continuous structural adaptation (remodeling) of blood vessels in response to several stimuli. Here, a theoretical model is presented that relates the structural and functional properties of microvascular networks to the adaptive responses of individual segments to hemodynamic and metabolic stimuli. All vessels are assumed to respond, according to a common set of adaptation rules, to changes in wall shear stress, circumferential wall stress, and tissue metabolic status (indicated by partial pressure of oxygen). An increase in vessel diameter with increasing wall shear stress and an increase in wall mass with increased circumferential stress are needed to ensure stable vascular adaptation. The model allows quantitative predictions of the effects of changes in systemic hemodynamic conditions or local adaptation characteristics on vessel structure and on peripheral resistance. Predicted effects of driving pressure on the ratio of wall thickness to vessel diameter are consistent with experimental observations. In addition, peripheral resistance increases by ≈65% for an increase in driving pressure from 50 to 150 mm Hg. Peripheral resistance is predicted to be markedly increased in response to a decrease in vascular sensitivity to wall shear stress, and to be decreased in response to increased tissue metabolic demand. This theoretical approach provides a framework for integrating available information on structural remodeling in the vascular system and predicting responses to changing conditions or altered vascular reactivity, as may occur in hypertension.
Nicorandil Promotes Myocardial Capillary and Arteriolar Growth in the Failing Heart of Dahl Salt-Sensitive Hypertensive Rats
Authors: Xu Jinglan , Nagata Kohzo , Obata Koji , Ichihara Sahoko , Izawa Hideo , Noda Akiko , Nagasaka Tetsuro , Iwase Mitsunori , Naoe Tomoki , Murohara Toyoaki , Yokota Mitsuhiro
Published: September 2005

Long-term administration of vasodilators increases shear stress, which is thought to be important for vascular growth in the heart. Nicorandil, an activator of ATP-sensitive potassium channels with a nitrate-like action, is a potent vasodilator. We have now investigated the effects of nicorandil on vascular growth and gene expression in the failing heart of Dahl salt-sensitive (DS) hypertensive rats. DS rats fed a high-salt diet from 6 weeks of age develop concentric cardiac hypertrophy secondary to hypertension at 11 weeks, followed by heart failure at 18 weeks. DS rats on such a diet were treated with a nonantihypertensive oral dose of nicorandil (6 mg/kg per day) or vehicle from 11 to 18 weeks of age. Treatment of DS rats with nicorandil improved cardiac function and attenuated the development of heart failure. Myocardial capillary and arteriolar densities did not differ between vehicle-treated DS rats and age-matched controls. The abundance of mRNAs for endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF), the VEGF receptor Flt-1, and basic fibroblast growth factor (bFGF) in the myocardium was markedly reduced in vehicle-treated DS rats compared with controls. Treatment of DS rats with nicorandil greatly increased capillary and arteriolar densities and inhibited the downregulation of eNOS, VEGF, fms-like tyrosin kinase-1, and bFGF gene expression. This, nicorandil stimulates coronary capillary and arteriolar growth and thereby likely suppresses the development of heart failure in DS rats. Nicorandil may prove beneficial for the treatment of hypertensive heart failure as well as of ischemic heart disease.
WNK1
Kinase Polymorphism and Blood Pressure Response to a Thiazide Diuretic
Authors: Turner Stephen T. , Schwartz Gary L. , Chapman Arlene B. , Boerwinkle Eric
Published: September 2005

Single nucleotide polymorphisms (SNPs) in genes encoding or influencing renal sodium transport systems were investigated as potential predictors of blood pressure (BP) response to a thiazide diuretic. A sample of 585 adults with essential hypertension (30 to 59.9 years of age; 50% blacks; 47% women) were treated with hydrochlorothiazide for 4 weeks (25 mg daily, orally) to determine office BP responses. Ambulatory BP responses were measured in a subset of 228 subjects. After adjustment for ethnicity, sex, age, and waist-to-hip ratio, 3 SNPs in
WNK1
(rs2107614, rs2277869, and rs1159744), encoding a lysine-deficient protein kinase that regulates thiazide-sensitive sodium-potassium cotransport, made statistically significant contributions to predicting ambulatory BP responses, accounting for 2% to 4% of variation in systolic and diastolic responses (
P
<0.05). SNPs in the β
2
-adrenoceptor (rs2400707) and the epithelial sodium channel γ-subunit (rs5723 and rs5729) were associated with similar magnitude of variation in ambulatory systolic BP response (
P
=0.028) or office diastolic BP response (
P
<0.05), respectively. However, SNPs evaluated in the furosemide-sensitive sodium-potassium chloride cotransporter, potassium inwardly rectifying channel, chloride channel, thiazide-sensitive sodium chloride cotransporter, epithelial sodium channel β-subunit, and the mineralocorticoid receptor were not associated with significant variation in ambulatory or office BP responses. Polymorphisms in genes regulating renal sodium transport, in particular
WNK1
, predict interindividual differences in antihypertensive responses to hydrochlorothiazide.
Rapid Heart Rate Increase at Onset of Exercise Predicts Adverse Cardiac Events in Patients With Coronary Artery Disease
Authors: Falcone Colomba , Buzzi Maria Paola , Klersy Catherine , Schwartz Peter J.
Published: September 2005

Background—

We previously demonstrated that reduced vagal activity and/or increased sympathetic activity identify post–myocardial infarction patients at high risk for cardiac mortality. Simple and inexpensive autonomic markers are necessary to perform autonomic screening in large populations. We tested our hypothesis that abnormally elevated heart rate (HR) responses at the onset of an exercise stress test, which imply rapid vagal withdrawal immediately preceding sympathetic activation, might predict adverse cardiac events in patients with documented coronary artery disease.

Methods and Results—

The HR increase during the first minute (ΔHR
1 minute
) of a symptom-limited exercise stress test was quantified in 458 patients with documented coronary artery disease. During a 6-year (interquartile range 3.7 to 9.0 years) follow-up, 71 patients experienced adverse cardiac events (21 cardiac deaths, 56 nonfatal myocardial infarctions). In univariate analysis, ΔHR
1 minute
≥12 bpm (above the median value of its distribution) predicted both adverse outcome and cardiac death with a hazard ratio of 5.0 (95% CI 2.7 to 9.1;
P
<0.0001) and of 15.6 (95% CI 2.0 to 118.7;
P
<0.001), respectively. After adjustment for potential confounders, ΔHR
1 minute
remained predictive for both combined end points and for cardiac death.

Conclusions—

A marked HR increase at the onset of a standard exercise stress test is a novel and easily available parameter that could be clinically useful as an independent predictor of adverse cardiac events, including death, among patients with documented coronary artery disease.
Role of the Protein Kinase C-ε–Raf-1–MEK-1/2–p44/42 MAPK Signaling Cascade in the Activation of Signal Transducers and Activators of Transcription 1 and 3 and Induction of Cyclooxygenase-2 After Ischemic Preconditioning
Authors: Xuan Yu-Ting , Guo Yiru , Zhu Yanqing , Wang Ou-Li , Rokosh Gregg , Messing Robert O. , Bolli Roberto
Published: September 2005

Background—

Although Janus kinase (JAK)–mediated Tyr phosphorylation of signal transducers and activators of transcription (STAT) 1 and 3 is essential for the upregulation of cyclooxygenase-2 (COX-2) and the cardioprotection of late preconditioning (PC), the role of Ser phosphorylation of STAT1 and STAT3 in late PC and the upstream signaling mechanisms responsible for mediating Ser phosphorylation of STAT1 and STAT3 remain unknown.

Methods and Results—

In mice preconditioned with six 4-minute coronary occlusion/4-minute reperfusion cycles, we found that (1) ischemic PC activates the Raf1–mitogen-activated protein kinase (MAPK)/extracellular signal–regulated kinase kinase (MEK) 1/2–p44/42 MAPK signaling pathway, induces phosphorylation of STAT1 and STAT3 on the Ser-727 residue, and upregulates COX-2 expression; (2) pSer-STAT1 and pSer-STAT3 form complexes with pTyr-p44/42 MAPKs in preconditioned myocardium, supporting the concept that Ser phosphorylation of these 2 factors is mediated by activated p44/42 MAPKs; and (3) activation of the Raf-1-MEK-1/2–p44/42 MAPK-pSer-STAT1/3 pathway and induction of COX-2 during ischemic PC are dependent on protein kinase C (PKC)-ε activity, as determined by both pharmacological and genetic inhibition of PKCε.

Conclusions—

To our knowledge, this is the first study to demonstrate that ischemic PC causes Ser phosphorylation of STAT1 and STAT3 and that this event is governed by PKCε via a PKCε–Raf1-MEK1/2-p44/42 MAPK pathway. Furthermore, this is the first report that COX-2 expression in the heart is controlled by PKCε. Together with our previous findings, the present study implies that STAT-dependent transcription of the genes responsible for ischemic PC is modulated by a dual signaling mechanism that involves both JAK1/2 (Tyr phosphorylation) and PKCε (Ser phosphorylation).
Rapamycin, but Not FK-506, Increases Endothelial Tissue Factor Expression
Authors: Steffel Jan , Latini Roberto A. , Akhmedov Alexander , Zimmermann Dorothee , Zimmerling Pamela , Lüscher Thomas F. , Tanner Felix C.
Published: September 2005

Background—

Drugs released from stents affect the biology of vascular cells. We examined the effect of rapamycin and FK-506 on tissue factor (TF) expression in human aortic endothelial cells (HAECs) and vascular smooth muscle cells (HAVSMCs).

Methods and Results—

Rapamycin enhanced thrombin- and tumor necrosis factor (TNF)-α–induced endothelial TF expression in a concentration-dependent manner. The maximal increase was 2.5-fold more pronounced than that by thrombin or TNF-α alone and was paralleled by a 1.4-fold higher TF surface activity compared with thrombin alone. Rapamycin by itself increased basal TF levels by 40%. In HAVSMCs, rapamycin did not affect thrombin- or TNF-α–induced TF expression. In contrast to rapamycin, FK-506 did not enhance thrombin- or TNF-α–induced endothelial TF expression. Thrombin induced a transient dephosphorylation of the mammalian target of rapamycin downstream target p70S6 kinase. Rapamycin completely abrogated p70S6 kinase phosphorylation, but FK-506 did not. FK-506 antagonized the effect of rapamycin on thrombin-induced TF expression. Rapamycin did not alter the pattern of p38, extracellular signal–regulated kinase, or c-Jun NH
2
-terminal kinase phosphorylation. Real-time polymerase chain reaction analysis revealed that rapamycin had no influence on thrombin-induced TF mRNA levels for up to 2 hours but led to an additional increase after 3 and 5 hours.

Conclusions—

Rapamycin, but not FK-506, enhances TF expression in HAECs but not in HAVSMCs. This effect requires binding to FK binding protein-12, is mediated through inhibition of the mammalian target of rapamycin, and partly occurs at the posttranscriptional level. These findings may be clinically relevant for patients receiving drug-eluting stents, particularly when antithrombotic drugs are withdrawn or ineffective, and may open novel perspectives for the design of such stents.
The World Was Watching—And Talking
Authors: Beom Khisu , Carlin Diana B. , Silver Mark D.
Published: September 2005

The 2004 U.S. presidential election was called one of the most important in history. The world’s only remaining superpower’s election captured international attention as never before. This article examines how international observers discussed the election via reactions to the debates by using DebateWatch transcripts and surveys. The study finds media framing in a person’s home country as well as a greater sense of globalization contributed to participants’ perspectives. Although participants were influenced by cultural and political issues in their home countries, they were also influenced by what they observed in the debates, and they demonstrated greater understanding of the U.S. electoral process, the candidates, and the issues.
Contrasts in Presidential Campaign Commercials of 2004
Authors: Devlin L. Patrick
Published: September 2005

This article examines television advertising used during the 2004 presidential campaign. Based on interviews with the advertising creators and coordinators and on repeated viewings by the author and his graduate and undergraduate students, it describes, analyzes, and evaluates the ads. The study reveals massive spending totaling $620 million—a 235% increase over 2000. Kerry, his party, and 527 groups supporting his candidacy outspent Bush, his party, and his 527 groups $358 million to $262 million. Kerry had double the Bush ads, mainly because of state-specific ad placement. Kerry stayed positive early and ended with more positive ads, whereas his 527s took up the negative attack against Bush. Bush ran the most negative campaign in presidential history. 527 group ads played a significant role in the campaign, both early and late in the campaign. These ads hurt both Kerry and Bush early and aided Bush in the closing days of the campaign.
Let the People Speak
Authors: McKinney Mitchell S.
Published: September 2005

This study argues that a “devolution” of the presidential town hall debate as public sphere has occurred, whereby every 4 years citizens’ freedom to participate in their debate—as they see fit—has been seriously restricted. The primary purpose of this study is to examine how well the town hall presidential debate, particularly in its current form, addresses issues of greatest concern to the American public. Specifically, to test how well the dialogue of a town hall debate matches the public’s campaign issue agenda, as well as examine possible changes over time, analysis compares the issues discussed in both the 2004 and 1992 town hall debates to the agenda of issues that citizens claimed were most important to them. Results suggest that as candidates have gained greater control over the town hall’s structure and resulting dialogue, the ability of this forum to reflect a citizen’s issue agenda has greatly diminished.
Lost in Translation
Authors: Orland-Barak Lily
Published: September 2005

Situated in the context of Israeli in-service education, this article explores the development of the author’s understanding of the process of learning to mentor from the acquisition of communicative competencies (as identified in an initial study), toward a more discursive view of the process as “participation in competing discourses of practice” (as identified in subsequent studies). Recent work has revealed the intricacies and complexities entailed in translating from one language (teaching) to another (mentoring), often positioning mentors as “lost in translation.” Specifically, studies shed light on issues of morality, expertise, context, and conditions for learning to mentor. To discuss the author’s evolving understandings, she attends to three interrelated themes: Mentoring as connected to teaching, mentoring as distinct from teaching, and conditions for learning to mentor. Finally, the author addresses the question, So what? to consolidate her emergent understandings of the metaphor, framed as assertions for thinking about the practice of mentoring.
Establishing Teaching as a Profession
Authors: Wise Arthur E.
Published: September 2005

The National Council for Accreditation of Teacher Education (NCATE) celebrated its 50th anniversary in 2004. In those 50 years, NCATE has become a learning community, growing and evolving as the knowledge base in teaching and learning has evolved. NCATE starts its second 50 years with a record 690 institutions in its system as accredited institutions, candidates, and precandidates. The central question at hand is a decision teacher educators must make. Will we move forward toward increased professionalization by working collectively to shape an increasing consensus on a common core of knowledge as it is explicated through professional standards? Or will we retreat to “private universes” in which we teach our own conceptions of knowledge about teaching and learning? In that case, the government will decide, in typically narrow fashion, what must be taught and, in some cases, how it must be taught. To avoid that future, we must work together as a profession to bring our differences to the table. NCATE is the teaching profession’s vehicle to do just that, and we look forward to working with institutions ready to make that commitment.
Toward Integrated Career Assessment: Using Story to Appraise Career Dispositions and Adaptability
Authors: Hartung Paul J. , Borges Nicole J.
Published: September 2005

This study examined the validity of using stories to appraise career dispositions and problems associated with career adaptability. Premedical students (63 women, 37 men) wrote narratives about Thematic Apperception Test cards (TAT) and responded to the Strong Interest Inventory (SII). Independent raters identified identical career adaptability dimensions from TAT stories more than 47% of the time. RIASEC codes derived from TAT responses matched measured codes on at least one theme 82% of the time. Results provided modest support for the reliability of using TAT card responses to derive a RIASEC personality type consistent with measured vocational interests. Further study to increase interrater reliability and hone the scoring scheme for deriving RIASEC codes might bolster the validity of using story to assess vocational personality dispositions and career problems. Ultimately, constructivist approaches could augment differential methods for appraising and fostering career exploration and choice in an integrated career assessment and counseling approach.
Battered Women’s Process of Leaving: Implications for Career Counseling
Authors: Brown Chris , Linnemeyer Rachel M. , Dougherty Whitney L. , Coulson Jaime C. , Trangsrud Heather B. , Farnsworth Ivy S.
Published: September 2005

Using consensual qualitative research, we considered how battered women’s intimate partner abuse and subsequent experiences and expectations of shelter services and assistance of the criminal justice system have affected their work and employment opportunities. Results indicated that participants expected shelters to assist them with finding housing and employment and regard law enforcement and the legal system to be quite ineffective in their response to domestic violence issues. Results also revealed that women expected to be abused following their partner’s alcohol or drug use and further noted that their partner’s patterns of abuse had either prevented or disrupted their employment. Participants expressed strong interest in finding work or pursuing a career and expected to complete educational and/or licensing requirements that were commensurate with their stated work/career goals. Finally, determined to not be abused by their partner again, participants aspire for a future of freedom and peace of mind, without their abuser, while focusing on reestablishing and building healthy relationships with their children. Implications for career counseling and research are discussed.
Qualitative Career Assessment: Developing the My System of Career Influences Reflection Activity
Authors: McMahon Mary , Watson Mark , Patton Wendy
Published: September 2005

This article reports on the development of a qualitative career assessment activity, the My System of Career Influences (MSCI) Reflection Activity. The article describes the process of developing and testing the instrument. The testing was conducted in two stages with adults and adolescents. Findings from Stage 1 indicate that the MSCI (pilot version) is a useful instrument that warrants separate versions for adults and adolescents. Findings from Stage 2 indicate that the MSCI (adolescent version) is a useful instrument that is appropriate for use with adolescents. Suggestions for future refinement and testing of the MSCI are presented.
3D and 4D Sonography History and Theory
Authors: Stephenson Susan Raatz
Published: September 2005

Static 3D and real-time 4D sonography is the newest technology to help sonographers acquire images and aid in the diagnosis of pathology. Touted as a fast and efficient method of collecting needed data within a data set, the potential for increased diagnostic confidence may be a reality. Three-dimensional imaging has been evolving since the early 1970s and has now come into the clinical setting. Understanding the development of this imaging format, current theory, and terminology helps the sonographer obtain and use an optimal data set.
Knowledge of Breast Self-Examination and Other Determinants’ Relationship on the Self-Rated Health of Elderly Women
Authors: Evans Kevin D. , Bates R. C.
Published: September 2005

This study examines whether the knowledge of breast self-examination (BSE) could be a significant contributor to elderly women’s self-rated health. Additional variables were considered as potential influences on their self-rated health. This research used a quasi-experimental design and random selection to assign assisted living facilities to treatment and control groups. Participants in this study were women, age 75 years and older. All participants were gauged for breast cancer risk as a pretest measurement. Only the experimental group of older women received BSE instruction and then provided their self-rated health eight weeks later. BSE knowledge contributed statistically to the experimental elderly women’s self-rated mental health scores. Instrumental activities of daily living were statistically significant for both groups at explaining variance in their physical health scores. This research study, although limited, points to the value of providing BSE to elderly women and its influence on their mental health.
Expression profiling of laser-microdissected intrapulmonary arteries in hypoxia-induced pulmonary hypertension
Authors: Kwapiszewska Grazyna , Wilhelm Jochen , Wolff Stephanie , Laumanns Isabel , Koenig Inke R , Ziegler Andreas , Seeger Werner , Bohle Rainer M , Weissmann Norbert , Fink Ludger
Published: September 2005

Background

Chronic hypoxia influences gene expression in the lung resulting in pulmonary hypertension and vascular remodelling. For specific investigation of the vascular compartment, laser-microdissection of intrapulmonary arteries was combined with array profiling.

Methods and Results

Analysis was performed on mice subjected to 1, 7 and 21 days of hypoxia (FiO2 = 0.1) using nylon filters (1176 spots). Changes in the expression of 29, 38, and 42 genes were observed at day 1, 7, and 21, respectively. Genes were grouped into 5 different classes based on their time course of response. Gene regulation obtained by array analysis was confirmed by real-time PCR. Additionally, the expression of the growth mediators PDGF-B, TGF-β, TSP-1, SRF, FGF-2, TIE-2 receptor, and VEGF-R1 were determined by real-time PCR. At day 1, transcription modulators and ion-related proteins were predominantly regulated. However, at day 7 and 21 differential expression of matrix producing and degrading genes was observed, indicating ongoing structural alterations. Among the 21 genes upregulated at day 1, 15 genes were identified carrying potential hypoxia response elements (HREs) for hypoxia-induced transcription factors. Three differentially expressed genes (S100A4, CD36 and FKBP1a) were examined by immunohistochemistry confirming the regulation on protein level. While FKBP1a was restricted to the vessel adventitia, S100A4 and CD36 were localised in the vascular tunica media.

Conclusion

Laser-microdissection and array profiling has revealed several new genes involved in lung vascular remodelling in response to hypoxia. Immunohistochemistry confirmed regulation of three proteins and specified their localisation in vascular smooth muscle cells and fibroblasts indicating involvement of different cells types in the remodelling process. The approach allows deeper insight into hypoxic regulatory pathways specifically in the vascular compartment of this complex organ.
Modeling the emergence of multi-protein dynamic structures by principles of self-organization through the use of 3DSpi, a multi-agent-based software
Authors: Soula Hédi , Robardet Céline , Perrin François , Gripon Sébastien , Beslon Guillaume , Gandrillon Olivier
Published: September 2005

Background

There is an increasing need for computer-generated models that can be used for explaining the emergence and predicting the behavior of multi-protein dynamic structures in cells. Multi-agent systems (MAS) have been proposed as good candidates to achieve this goal.

Results

We have created 3DSpi, a multi-agent based software that we used to explore the generation of multi-protein dynamic structures. Being based on a very restricted set of parameters, it is perfectly suited for exploring the minimal set of rules needed to generate large multi-protein structures. It can therefore be used to test the hypothesis that such structures are formed and maintained by principles of self-organization. We observed that multi-protein structures emerge and that the system behavior is very robust, in terms of the number and size of the structures generated. Furthermore, the generated structures very closely mimic spatial organization of real life multi-protein structures.

Conclusion

The behavior of 3DSpi confirms the considerable potential of MAS for modeling subcellular structures. It demonstrates that robust multi-protein structures can emerge using a restricted set of parameters and allows the exploration of the dynamics of such structures. A number of easy-to-implement modifications should make 3DSpi the virtual simulator of choice for scientists wishing to explore how topology interacts with time, to regulate the function of interacting proteins in living cells.
MAOA haplotypes associated with thrombocyte-MAO activity
Authors: Jansson Mårten , McCarthy Shane , Sullivan Patrick F , Dickman Paul , Andersson Björn , Oreland Lars , Schalling Martin , Pedersen Nancy L
Published: September 2005

Background

The aim was to ascertain whether thrombocyte MAO (trbc-MAO) activity and depressed state are genetically associated with the MAO locus on chromosome X (Xp11.3 – 11.4). We performed novel sequencing of the MAO locus and validated genetic variants found in public databases prior to constructing haplotypes of the MAO locus in a Swedish sample (N = 573 individuals).

Results

Our results reveal a profound SNP desert in the MAOB gene. Both the MAOA and MAOB genes segregate as two distinct LD blocks. We found a significant association between two MAOA gene haplotypes and reduced trbc-MAO activity, but no association with depressed state.

Conclusion

The MAO locus seems to have an effect on trbc-MAO activity in the study population. The findings suggest incomplete X-chromosome inactivation at this locus. It is plausible that a gene-dosage effect can provide some insight into the greater prevalence of depressed state in females than males.
Adaptive designs based on the truncated product method
Authors: Neuhäuser Markus , Bretz Frank
Published: September 2005

Background

Adaptive designs are becoming increasingly important in clinical research. One approach subdivides the study into several (two or more) stages and combines the p-values of the different stages using Fisher's combination test.

Methods

Alternatively to Fisher's test, the recently proposed truncated product method (TPM) can be applied to combine the p-values. The TPM uses the product of only those p-values that do not exceed some fixed cut-off value. Here, these two competing analyses are compared.

Results

When an early termination due to insufficient effects is not appropriate, such as in dose-response analyses, the probability to stop the trial early with the rejection of the null hypothesis is increased when the TPM is applied. Therefore, the expected total sample size is decreased. This decrease in the sample size is not connected with a loss in power. The TPM turns out to be less advantageous, when an early termination of the study due to insufficient effects is possible. This is due to a decrease of the probability to stop the trial early.

Conclusion

It is recommended to apply the TPM rather than Fisher's combination test whenever an early termination due to insufficient effects is not suitable within the adaptive design.
Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer
Authors: Lopez-Graniel Carlos , Dolores Rigoberto , Cetina Lucely , Gonzalez Aaron , Cantu David , Chanona Jose , Uribe Jesus , Candelaria Myrna , Brom Rocio , de la Garza Jaime , Duenas-Gonzalez Alfonso
Published: September 2005

Background

Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection.

Methods

Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method.

Results

Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration.

Conclusion

Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed.
Usefulness of PKH fluorescent labelling to study leukemic cell proliferation with various cytostatic drugs or acetyl tetrapeptide – AcSDKP
Authors: Boutonnat Jean , Faussat Anne-Marie , Marie Jean-Pierre , Bignon Jérôme , Wdzieczak-Bakala Johanna , Barbier Magali , Thierry Josiane , Ronot Xavier , Colle Pierre-Emmanuel
Published: September 2005

Background

PKH67 labelling was compared for classical proliferation assessment (using S phase evaluation) to analyse the cell proliferation of 29 AML patients treated or not with various drugs. Among these drugs, the effect of tetrapeptide AcSDKP or AcSDKP-NH2 on AML cells, stimulated or not by cytokines, was also evaluated in order to determine (i) if AcSDKP was able to inhibit blast cell proliferation as it inhibits haematopoietic progenitors (ii) if AcSDKP-NH2 was more stable than AcSDKP with FBS.

Methods

For PKH labeling, cells were suspended in Diluent C, and rapidly admixed with PKH67 solution at 20 μM PKH67. Staining was stopped by addition of FBS.

Results

A good correlation between PKH67 labelling and bromodeoxyuridine incorporation was obtained first with 6/9 patients for control cells, then for 11/17 AML patients treated with classical antileukemic drugs (among whom 4 were also treated with AcSDKP). The effect of AcSDKP was also studied on 7 patients. The discrepancy between both methods was essentially due to an accumulation of cells into different cycle phases measured by BrdUrd incorporation secondary to drug action and PKH67 labelling which measured the dynamic proliferation. This last method allows identifying resistant cells which still proliferate. AcSDKP or AcSDKP-NH2 induced a decrease of leukemic cell proliferation in 5/7 patients when cytokines were added (in order to stimulate proliferation) one day after tetrapeptide AcSDKP or AcSDKP-NH2. No effect on proliferation was noted when cytokines were added to AcSDKP-NH2.

Conclusion

PKH67 labelling method is a powerful tool for cell proliferation assessment in patients with AML, even in cells treated by various drugs.
Public beliefs about causes and risk factors for mental disorders: a comparison of Japan and Australia
Authors: Nakane Yoshibumi , Jorm Anthony F , Yoshioka Kumiko , Christensen Helen , Nakane Hideyuki , Griffiths Kathleen M
Published: September 2005

Background

Surveys of the public in a range of Western countries have shown a predominant belief in social stressors as causes of mental disorders. However, there has been little direct cross-cultural comparison. Here we report a comparison of public beliefs about the causes of mental disorders in Japan and Australia.

Methods

Surveys of the public were carried out in each country using as similar a methodology as feasible. In both countries, household interviews were carried out concerning beliefs about causes and risk factors in relation to one of four case vignettes, describing either depression, depression with suicidal thoughts, early schizophrenia or chronic schizophrenia. In Japan, the survey involved 2000 adults aged between 20 and 69 from 25 regional sites spread across the country. In Australia, the survey involved a national sample of 3998 adults aged 18 years or over.

Results

In both countries, both social and personal vulnerability causes were commonly endorsed across all vignettes. The major differences in causal beliefs were that Australians were more likely to believe in infection, allergy and genetics, while Japanese were more likely to endorse "nervous person" and "weakness of character". For risk factors, Australians tended to believe that women, the young and the poor were more at risk of depression, but these were not seen as higher risk groups by Japanese.

Conclusion

In both Japan and Australia, the public has a predominant belief in social causes and risk factors, with personal vulnerability factors also seen as important. However, there are also some major differences between the countries. The belief in weakness of character as a cause, which was stronger in Japan, is of particular concern because it may reduce the likelihood of seeking professional help and support from others.
Acute unilateral hearing loss as an unusual presentation of cholesteatoma
Authors: Thio Daniel , Ahmed Shahzada K , Bickerton Richard C
Published: September 2005

Background

Cholesteatomas are epithelial cysts that contain desquamated keratin. Patients commonly present with progressive hearing loss and a chronically discharging ear. We report an unusual presentation of the disease with an acute hearing loss suffered immediately after prolonged use of a pneumatic drill.

Case presentation

A 41 year old man with no previous history of ear problems presented with a sudden loss of hearing in his right ear immediately following the prolonged use of a pneumatic drill on concrete.

The cause was found to be a fractured long process of incus which had been eroded by the presence of an attic cholesteatoma.

A tympanomastoidectomy and ossiculoplasty was performed with good result.

Conclusion

Cholesteatomas may be asymptomatic and insidious in their onset. This case illustrates the point that an indolent disease such as this may present in unusual ways and the clinician must always have a high index of suspicion combined with thorough assessment and examination of every patient.