bluuebunny/crossref_metadata_2025 huggingface dataset:
The Absolute Risk of Cervical Abnormalities in High-risk Human Papillomavirus–Positive, Cytologically Normal Women Over a 10-Year Period
Authors: Kjaer Susanne , Høgdall Estrid , Frederiksen Kirsten , Munk Christian , van den Brule Adriaan , Svare Edith , Meijer Chris , Lorincz Attilla , Iftner Thomas
Published: October 2006

In spite of the success of cervical cytology as a cancer-screening tool, it has important limitations, and human papillomavirus (HPV) testing may be valuable in future screening. The majority of women in screened populations, who test HPV positive, will have a concurrent normal smear, and we need more information about the risk for subsequent high-grade cervical lesions in these women. We examined 8,656 younger women (22–32 years old) and 1,578 older women (40–50 years old) who were followed for development of cervical neoplasia (cytology and/or histology) through the Danish Pathology Data Bank. We estimated the proportion of women developing cervical lesions of different types before a given time point as a function of time. Among women with normal cytology and positive high-risk Hybrid Capture 2 (HC2) test, 17.7% and 24.5% of younger and older women, respectively, had a subsequent abnormal Pap smear within 5 years. The risk of CIN3 or cancer within 10 years among younger women with positive HC2 test was 13.6% (10.9–16.2) and 21.2% (2.7–36.1) among older women. An analysis among younger women also being HC2-positive 2 years before baseline showed a subsequent 10-year risk of ≥CIN3 of 18% (14.6–21.5). Among older women where HPV may be added to general screening, the estimated absolute risk of ≥CIN3 in HC2-positive women was more than 20% within 10 years. These results indicate that even a single positive HPV test in cytologically negative women is substantially predictive of high-grade CIN and suggest that HC2 testing can help stratify women into different risk categories. (Cancer Res 2006; 66(21): 10630-6)
When to Give? A Note on the Timing of Gifts and Bequests
Authors: Jousten Alain
Published: October 2006

We generalise the standard joy-of-giving bequest motive by including inter vivos gifts. Within a life-cycle framework, we analyse the implications of the choice of different discount factors for the utility of gifts and bequests. For a linear utility of giving, we characterise the gift and bequest pattern of a liquidity constrained individual over the life-cycle. We find that discounting at the interest rate is very convenient as the linear utility parameter can be interpreted as a summary measure for the strength of the motive of giving, net of all gift and bequest timing issues over the life-cycle.
Creating a Contrastive Rhetorical Stance
Authors: Mei Wu Siew
Published: October 2006

It is often the case that undergraduates writing essays to fulfil course requirements have an academic audience (i.e. lecturer/s marking the essay) as their target readers. These texts may represent a form of academic writing by novice writers in the process of learning academic discourse and conventions. Though these texts may not be comparable to professional academic writing, the aspect of the maintenance of a good balance between objectivity and the portrayal of an evaluative stance is of interest in this genre too (Hunston 1989; Hunston and Thompson 2000).

This paper investigates undergraduate students’ efforts to portray a contrastive stance through the strategy of problematization (Barton 1993) in argumentative essays. More specifically, it compares how writers of high-rated and low-rated essays problematize issues in more or less effective ways. Using the engagement system of the Appraisal framework (White 1998; Martin 1992; Martin and Rose 2003), this study analyses the evaluative resources used by the writers to achieve more or less successful problematization of issues discussed. The results indicate a more strategic and appropriate use of evaluative resources by the writers of high-rated scripts to create clear lines of contrastive positions. On the basis of the analysis, some pedagogical implications are discussed.
Language Socialization of the Child through Caretaker-Child Personal Narratives
Authors: Winskel Heather , Luksaneeyanawin Sudaporn , Yangklang Peerapat
Published: October 2006

The present study reports preliminary findings on the elicitation strategies used by Thai and English caretakers when eliciting past event narratives from pre-schoolers. Ten Thai and ten English-speaking caretaker-child dyads were recruited from Bangkok, Thailand and from Sydney, Australia. Caretakers were asked to elicit past event narratives from their children and the three best narratives were selected for analysis. Elicitation strategies used by caretakers were coded into various categories based on McCabe and Peterson (1991), Minami (2002) and Chang (2003). Results revealed common and culture-specific strategies. English-speaking caretakers in general provided more information, requested more evaluation, expressed more agreement and approval, revised and corrected children, whereas Thai caretakers used more contextual, temporal information. Results are discussed in terms of educational implications and future research directions.
Feasibility of preoperative inspiratory muscle training in patients undergoing coronary artery bypass surgery with a high risk of postoperative pulmonary complications: a randomized controlled pilot study
Authors: Hulzebos Erik HJ , van Meeteren Nico LU , van den Buijs Bram JWM , de Bie Rob A , de la Rivière A Brutel , Helders Paul JM
Published: October 2006

Objective: To determine in a pilot study the feasibility and effects of preoperative inspiratory muscle training in patients at high risk of postoperative pulmonary complications who were scheduled for coronary artery bypass graft surgery.

Design: Single-blind, randomized controlled pilot study.

Setting: University Medical Centre Utrecht, the Netherlands.

Subjects: Twenty-six patients at high risk of postoperative pulmonary complications were selected.

Intervention: The intervention group ( N = 14) received 2-4 weeks of preoperative inspiratory muscle training on top of the usual care received by the patients in the control group.

Main measures: Primary outcome variables of feasibility were the occurrence of adverse events, and patient satisfaction and motivation. Secondary outcome variables were postoperative pulmonary complications and length of hospital stay.

Results: The feasibility of inspiratory muscle training was good and no adverse events were observed. Treatment satisfaction and motivation, scored on 10-point scales, were 7.9 (± 0.7) and 8.2 (± 1.0), respectively. Postoperative atelectasis occurred in significantly fewer patients in the intervention group than in the control group (ϰ2DF1 = 3.85; P = 0.05): Length of hospital stay was 7.93 (± 1.94) days in the intervention group and 9.92 (± 5.78) days in the control group ( P = 0.24).

Conclusion: Inspiratory muscle training for 2-4 weeks before coronary artery bypass graft surgery was well tolerated by patients at risk of postoperative pulmonary complications and prevented the occurrence of atelectasis in these patients. A larger randomized clinical trial is warranted.
The usability of six physical performance tasks in a rehabilitation population with chronic low back pain
Authors: Smeets Rob JEM , Hijdra Helma JM , Kester Arnold DM , Hitters Minou WGC , Knottnerus J André
Published: October 2006

Objective: To examine the influence of task experience on the difference between test and retest and to assess test-retest reliability and limits of agreement of six performance tasks in chronic low back pain patients. These measures will be used to define the clinical usability.

Design: Test-retest of six performance tasks in a group of patients with no experience and a group of patients after previous experience with these tasks.

Setting: Three rehabilitation centres.

Subjects: Fifty-three patients with non-specific chronic low back pain.

Main measures: Five-minute walking, 50-ft (15 m) fast walking, sit-to-stand, loaded forward reach, 1-min stair-climbing and Progressive Isoinertial Lifting Evaluation (PILE). To assess the influence of task experience, differences between test and retest between both groups were tested using Mann-Whitney test. For both groups together, intraclass correlation coefficients (ICCs) and the limits of agreement using Bland and Altman plots were calculated.

Results: Thirty patients with no task experience and 23 patients who had already undertaken the tasks on at least two occasions participated. Both groups showed similar differences between test and retest. The test-retest reliability for the total study population was good to very high: ICC varied from 0.74 to 0.99. For the total study population, the limits of agreement expressed as percentage of the mean score of each task was low to moderate for 5-min walking and 1-min stair-climbing (21% and 20% respectively), moderate for 50-ft (15 m) fast walking, sit-to-stand and forward reach (33%, 29% and 36% respectively) and high for the PILE (48%).

Conclusions: Task experience did not significantly influence test-retest differences. All tasks showed sufficient test-retest reliability. Based on the natural variability of the tasks, the 5-min walking and stair-climbing task, and to a lesser degree the 50-ft (15 m) walking, sit-to-stand and loaded forward reach, seem clinically useful. There are major concerns about the usability of the PILE.
Restaurant Franchisees’ View of the Relationships Among the Determinants of Franchisors’ Entrepreneurial Strategy Processes
Authors: Sul Hoon-Ku , Khan Mahmood A.
Published: October 2006

The determinants of entrepreneurial strategy processes in franchising were identified as external environment, entrepreneurial strategy, mechanistic-organic structure, and financial performance. The primary purpose of this study was to explore a model that examines the relationships among the external environment, entrepreneurial strategy, mechanistic-organic structure, and financial performance of restaurant franchisors from the perspective of the franchisees. Structural equation modeling (SEM) was employed to develop this exploratory model. The final structural model indicated that franchisors’ external environment forces such as competition, politics, technology, and price wars are perceived as having a negative effect on franchisor’s financial performances. Restaurant franchisees perceive that franchisors’ entrepreneurial strategies such as aggressive expansion of franchise units, innovative system development, and menu development to meet local needs make a highly positive contribution to franchisors’ financial performance. Franchisees also perceived that franchisors’ entrepreneurial strategies and mechanistic-organic structure could have a significantly and mutually positive effect on each other.
Cooperation between VEGF and β3 integrin during cardiac vascular development
Authors: Weis Sara M. , Lindquist Jeffrey N. , Barnes Leo A. , Lutu-Fuga Kimberly M. , Cui Jianhua , Wood Malcolm R. , Cheresh David A.
Published: October 2006

In the developing myocardium, vascular endothelial growth factor (VEGF)–dependent neovascularization occurs by division of existing vessels, a process that persists for several weeks following birth. During this remodeling phase, mRNA expression of β3 integrin in the heart decreases significantly as vessel maturation progresses. However, in male mice lacking β3, coronary capillaries fail to mature and continue to exhibit irregular endothelial thickness, endothelial protrusions into the lumen, and expanded cytoplasmic vacuoles. Surprisingly, this phenotype was not seen in female β3-null mice. Enhanced VEGF signaling contributes to the β3-null phenotype, because these vessels can be normalized by inhibitors of VEGF or Flk-1. Moreover, intravenous injection of VEGF induces a similar angiogenic phenotype in hearts of adult wild-type mice. These findings show a clear vascular phenotype in the hearts of mice lacking β3 and suggest this integrin plays a critical role in coronary vascular development and the vascular response to VEGF.
The induction of Bim expression in human T-cell blasts is dependent on nonapoptotic Fas/CD95 signaling
Authors: Bosque Alberto , Aguiló Juan Ignacio , Alava M. Angeles , Paz-Artal Estela , Naval Javier , Allende Luis M. , Anel Alberto
Published: October 2006

The BH3-only protein Bim is required for maintaining the homeostasis of the immune system, since Bim regulates the down-modulation of T-cell responses, mainly through cytokine deprivation. Using T-cell blasts from healthy donors and also from patients with autoimmune lymphoproliferative syndromes (ALPSs) due to homozygous loss-of-function mutation of FasL (ALPS-Ic) or heterozygous mutation in the Fas/CD95 death domain (ALPS-Ia), it is shown that the induction of Bim expression during the process of human T-cell blast generation is strictly dependent on FasL/Fas-mediated signaling. The main pathway by which Fas signaling regulates the levels of Bim expression in human T-cell blasts is the death-domain– and caspase-independent generation of discrete levels of H2O2, which results in the net increase of Foxo3a levels. The present results connect the 2 main pathways described until the moment for the control of T-cell responses: death receptor–mediated activation-induced cell death and apoptosis by cytokine deprivation.
The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis
Authors: Tober Joanna , Koniski Anne , McGrath Kathleen E. , Vemishetti Radhika , Emerson Rachael , de Mesy-Bentley Karen K. L. , Waugh Richard , Palis James
Published: October 2006

In the adult, platelets are derived from unipotential megakaryocyte colony-forming cells (Meg-CFCs) that arise from bipotential megakaryocyte/erythroid progenitors (MEPs). To better define the developmental origin of the megakaryocyte lineage, several aspects of megakaryopoiesis, including progenitors, maturing megakaryocytes, and circulating platelets, were examined in the murine embryo. We found that a majority of hemangioblast precursors during early gastrulation contains megakaryocyte potential. Combining progenitor assays with immunohistochemical analysis, we identified 2 waves of MEPs in the yolk sac associated with the primitive and definitive erythroid lineages. Primitive MEPs emerge at E7.25 along with megakaryocyte and primitive erythroid progenitors, indicating that primitive hematopoiesis is bilineage in nature. Subsequently, definitive MEPs expand in the yolk sac with Meg-CFCs and definitive erythroid progenitors. The first GP1bβ-positive cells in the conceptus were identified in the yolk sac at E9.5, while large, highly reticulated platelets were detected in the embryonic bloodstream beginning at E10.5. At this time, the number of megakaryocyte progenitors begins to decline in the yolk sac and expand in the fetal liver. We conclude that the megakaryocyte lineage initially originates from hemangioblast precursors during early gastrulation and is closely associated both with primitive and with definitive erythroid lineages in the yolk sac prior to the transition of hematopoiesis to intraembryonic sites.
Postgenomic up-regulation of CCL3L1 expression in HTLV-2–infected persons curtails HIV-1 replication
Authors: Pilotti Elisabetta , Elviri Lisa , Vicenzi Elisa , Bertazzoni Umberto , Re Maria Carla , Allibardi Sonia , Poli Guido , Casoli Claudio
Published: October 2006

Leukocytes of persons coinfected with HTLV-2 and HIV-1 secrete chemokines that prevent CCR5-dependent (R5) HIV-1 infection of CD4+ T cells and macrophages, with HTLV-2–induced MIP-1α as dominant HIV-1 inhibitory molecule. Two nonallelic genes code for CCL3 and CCL3L1 isoforms of MIP-1α, and the population-specific copy number of CCL3L1 exerts a profound effect on HIV-1 susceptibility and disease progression. Here, we demonstrate that CCL3L1 is secreted spontaneously by leukocytes of HTLV-2–infected persons and superinduced when cells of HTLV-2/HIV-1 multiply exposed-uninfected seronegative (MEU) persons were stimulated with HIV-1 Env peptides. The CCL3L1 median copy number in MEU, HTLV-2/HIV-1–coinfected long-term nonprogressors (LTNPs) and HIV-1–monoinfected LTNPs were 1, 2, and 3, respectively. An increased CCL3L1/CCL3 mRNA ratio versus PHA-activated healthy leukocytes was observed in both HIV-1–monoinfected LTNPs and in HTLV-2/HIV-1MEU subjects. An additional potential correlate of HTLV-2 infection was a rapid and persistent leukocyte secretion of GM-CSF and IFN-γ, 2 cytokines endowed with CCR5 down-regulation capacity. This study confirms a crucial protective role of CCL3L1 from both HIV infection and disease progression, highlighting a previously not described functional up-regulation of this chemokine variant in both HIV-positive and -negative persons infected with HTLV-2.
Surgical treatment and prognostic analysis for gastrointestinal stromal tumors (GISTs) of the small intestine: before the era of imatinib mesylate
Authors: Wu Ting-Jung , Lee Li-Yu , Yeh Chun-Nan , Wu Pei-Yu , Chao Tzu-Chieh , Hwang Tsann-Long , Jan Yi-Yin , Chen Miin-Fu
Published: October 2006

Background

Gastrointestinal stromal tumors (GISTs), the most common type of mesenchymal tumors of the gastrointestinal (GI) tract, demonstrate positive kit staining. We report our surgical experience with 100 small intestine GIST patients and identify predictors for long-term disease-free survival (DFS) and overall survival (OS) to clarify the difference between high- and low-risk patients.

Methods

The clinicopathologic and follow-up records of 100 small intestine GIST patients who were treated at Chung Gung Memorial Hospital between 1983 and 2002 were retrospectively reviewed. Clinical and pathological factors were assessed for long-term DFS and OS by using a univariate log-rank test and a multivariate Cox proportional hazard model.

Results

The patients included 52 men and 48 women. Their ages ranged from 27 to 82 years. Among the 85 patients who underwent curative resection, 44 (51.8%) developed disease recurrence (liver metastasis was the most common form of recurrence). The follow-up period ranged from 5 to 202 months (median: 33.2 months). The 1-, 3-, and 5-year DFS and OS rates were 85.2%, 53.8%, and 43.7%, and 91.5%, 66.6%, and 50.5%, respectively. Using multivariate analysis, it was found that high tumor cellularity, mitotic count >5/50 high-power field, and a Ki-67 index ≧10% were three independent factors that were inversely associated with DFS. However, absence of tumor perforation, mitotic count < 5/50 high power field, and tumor with low cellularity were predictors of long-term favorable OS.

Conclusion

Tumors with low cellularity, low mitotic count, and low Ki-67 index, which indicate low risk, predict a more favorable DFS for small intestine GIST patients undergoing curative resection. Absence of tumor perforation with low mitotic count and low cellularity, which indicates low risk, can predict long-term OS for small intestine GIST patients who have undergone curative resection.
Changes in practice patterns affecting in-hospital and post-discharge survival among ACS patients
Authors: Stommel Manfred , Olomu Ade , Holmes-Rovner Margaret , Corser William , Gardiner Joseph C
Published: October 2006

Background

Adherence to clinical practice guidelines for the treatment of specific illnesses may result in unexpected outcomes, given that multiple therapies must often be given to patients with diverse medical conditions. Yet, few studies have presented empirical evidence that quality improvement (QI) programs both change practice by improving adherence to guidelines and improve patient outcomes under the conditions of actual practice. Thus, we focus on patient survival, following hospitalization for acute coronary syndrome in three successive patient cohorts from the same community hospitals, with a quality improvement intervention occurring between cohorts two and three.

Methods

This study is a comparison of three historical cohorts of Acute Coronary Syndrome (ACS) patients in the same five community hospitals in 1994–5, 1997, 2002–3. A quality improvement project, the Guidelines Applied to Practice (GAP), was implemented in these hospitals in 2001.

Study participants were recruited from community hospitals located in two Michigan communities during three separate time periods. The cohorts comprise (1) patients enrolled between December 1993 and April 1995 (N = 814), (2) patients enrolled between February 1997 and September 1997 (N = 452), and (3) patients enrolled between January 14, 2002 and April 13, 2003 (N = 710).

Mortality data were obtained from Michigan's Bureau of Vital Statistics for all three patient cohorts. Predictor variables, obtained from medical record reviews, included demographic information, indicators of disease severity (ejection fraction), co-morbid conditions, hospital treatment information concerning most invasive procedures and the use of ace-inhibitors, beta-blockers and aspirin in the hospital and as discharge recommendations.

Results

Adjusted in-hospital mortality showed a marked improvement with a HR = 0.16 (p < 0.001) comparing 2003 patients in the same hospitals to those 10 years earlier. Large gains in the in-hospital mortality were maintained based on 1-year mortality rates after hospital discharge.

Conclusion

Changes in practice patterns that follow recommended guidelines can significantly improve care for ACS patients. In-hospital mortality gains were maintained in the year following discharge.
Allelic dimorphism of Plasmodium vivax gam-1 in the Indian subcontinent
Authors: Prajapati Surendra K , Verma Anju , Adak Tridibes , Yadav Rajpal S , Kumar Ashwini , Eapen Alex , Das Manoj K , Singh Neeru , Sharma Surya K , Rizvi Moshahid A , Dash Aditya P , Joshi Hema
Published: October 2006

Background

Genetic polymorphism is an inevitable component of a complex organism especially in multistage infectious organisms such as malaria parasites. Understanding the population genetic structure of the parasites would provide valuable information for effective malaria control strategies. Recently, the development of molecular tools like PCR has made analysis of field samples possible and easier and research on Plasmodium vivax has also been strengthened. Not many reports are available on the genetic polymorphism of P. vivax from the Indian sub-continent. This study evaluates the extent of diversity in field isolates of India with respect to Pvgam-1.

Methods

A study was designed to assess the diversity of Pvgam-1 among field isolates from India, using a nested PCR assay. Field isolates were collected from different regions of the country and the observed variability was confirmed by sequencing data.

Results

Both Belem and Chesson type alleles were present either exclusively or in mixed form among isolates of all 10 study sites. The Belem type allele was predominant, occurring in 67% of isolates. The proportion of isolates showing the mixed form (both Belem and Chesson type alleles occurring together in the same isolate) was about 13 overall (up to 38.5% in some isolates). Sequencing of the PCR-amplified Belem and Chesson type alleles confirmed the PCR results. Among the 10 study sequences, 11 polymorphic sites and four singleton variations were observed. All the nucleotide substitutions were non-synonymous.

Conclusion

Study shows limited diversity of Pvgam-1 marker in Indian isolates with well representation of both Belem and Chesson type alleles.
Alpha-actinin-binding antibodies in relation to systemic lupus erythematosus and lupus nephritis
Authors: Becker-Merok Andrea , Kalaaji Manar , Haugbro Kaia , Nikolaisen Cathrin , Nilsen Kirsten , Rekvig Ole Petter , Nossent Johannes C
Published: October 2006

This study investigated the overall clinical impact of anti-α-actinin antibodies in patients with pre-selected autoimmune diseases and in a random group of anti-nuclear antibody (ANA)-positive individuals. The relation of anti-α-actinin antibodies with lupus nephritis and anti-double-stranded DNA (anti-dsDNA) antibodies represented a particular focus for the study. Using a cross-sectional design, the presence of antibodies to α-actinin was studied in selected groups, classified according to the relevant American College of Rheumatology classification criteria for systemic lupus erythematosus (SLE) (n = 99), rheumatoid arthritis (RA) (n = 68), Wegener's granulomatosis (WG) (n = 85), and fibromyalgia (FM) (n = 29), and in a random group of ANA-positive individuals (n = 142). Renal disease was defined as (increased) proteinuria with haematuria or presence of cellular casts. Sera from SLE, RA, and Sjøgren's syndrome (SS) patients had significantly higher levels of anti-α-actinin antibodies than the other patient groups. Using the geometric mean (± 2 standard deviations) in FM patients as the upper cutoff, 20% of SLE patients, 12% of RA patients, 4% of SS patients, and none of the WG patients were positive for anti-α-actinin antibodies. Within the SLE cohort, anti-α-actinin antibody levels were higher in patients with renal flares (p = 0.02) and correlated independently with anti-dsDNA antibody levels by enzyme-linked immunosorbent assay (p < 0.007) but not with other disease features. In the random ANA group, 14 individuals had anti-α-actinin antibodies. Of these, 36% had SLE, while 64% suffered from other, mostly autoimmune, disorders. Antibodies binding to α-actinin were detected in 20% of SLE patients but were not specific for SLE. They correlate with anti-dsDNA antibody levels, implying in vitro cross-reactivity of anti-dsDNA antibodies, which may explain the observed association with renal disease in SLE.
CD44+/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis
Authors: Sheridan Carol , Kishimoto Hiromitsu , Fuchs Robyn K , Mehrotra Sanjana , Bhat-Nakshatri Poornima , Turner Charles H , Goulet Robert , Badve Sunil , Nakshatri Harikrishna
Published: October 2006

Introduction

A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells has the unique ability to invade, home, and proliferate at sites of metastasis.

Methods

CD44 and CD24 expression was determined by flow cytometry. Northern blotting was used to determine the expression of proinvasive and 'bone and lung metastasis signature' genes. A matrigel invasion assay and intracardiac inoculation into nude mice were used to evaluate invasion, and homing and proliferation at sites of metastasis, respectively.

Results

Five among 13 breast cancer cell lines examined (MDA-MB-231, MDA-MB-436, Hs578T, SUM1315, and HBL-100) contained a higher percentage (>30%) of CD44+/CD24- cells. Cell lines with high CD44+/CD24- cell numbers express basal/mesenchymal or myoepithelial but not luminal markers. Expression levels of proinvasive genes (IL-1α, IL-6, IL-8, and urokinase plasminogen activator [UPA]) were higher in cell lines with a significant CD44+/CD24- population than in other cell lines. Among the CD44+/CD24--positive cell lines, MDA-MB-231 has the unique property of expressing a broad range of genes that favor bone and lung metastasis. Consistent with previous studies in nude mice, cell lines with CD44+/CD24- subpopulation were more invasive than other cell lines. However, only a subset of CD44+/CD24--positive cell lines was able to home and proliferate in lungs.

Conclusion

Breast cancer cells with CD44+/CD24- subpopulation express higher levels of proinvasive genes and have highly invasive properties. However, this phenotype is not sufficient to predict capacity for pulmonary metastasis.
Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages
Authors: Puppo Maura , Bosco Maria Carla , Federico Maurizio , Pastorino Sandra , Varesio Luigi
Published: October 2006

Hypoxia, a local decrease in oxygen tension, occurring in many pathological processes, modifies macrophage (Mφ) gene expression and function. Here, we provide the first evidence that hypoxia inhibits transgene expression driven by the Moloney murine leukemia virus-long terminal repeats (MoMLV-LTR) in IFN-γ-activated Mφ. Hypoxia silenced the expression of several MoMLV-LTR-driven genes, including v-myc, enhanced green fluorescence protein, and env, and was effective in different mouse Mφ cell lines and on distinct MoMLV backbone-based viruses. Down-regulation of MoMLV mRNA occurred at the transcriptional level and was associated with decreased retrovirus production, as determined by titration experiments, suggesting that hypoxia may control MoMLV retroviral spread through the suppression of LTR activity. In contrast, genes driven by the CMV or the SV40 promoter were up-regulated or unchanged by hypoxia, indicating a selective inhibitory activity on the MoMLV promoter. It is interesting that hypoxia was ineffective in suppressing MoMLV-LTR-controlled gene expression in T or fibroblast cell lines, suggesting a Mφ lineage-selective action. Finally, we found that MoMLV-mediated gene expression in Mφ was also inhibited by picolinic acid, a tryptophan catabolite with hypoxia-like activity and Mφ-activating properties, suggesting a pathophysiological role of this molecule in viral resistance and its possible use as an antiviral agent.
Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury
Authors: Tsung Allan , Zheng Ning , Jeyabalan Geetha , Izuishi Kunihiko , Klune John R , Geller David A , Lotze Michael T , Lu Lina , Billiar Timothy R
Published: October 2006

Endogenous ligands released from damaged cells, so-called damage-associated molecular pattern molecules (DAMPs), activate innate signaling pathways including the TLRs. We have shown that hepatic, warm ischemia and reperfusion (I/R) injury, generating local, noninfectious DAMPs, promotes inflammation, which is largely TLR4-dependent. Here, we demonstrate that increasing dendritic cell (DC) numbers enhance inflammation and organ injury after hepatic I/R. High-mobility group box 1 (HMGB1), a NF released by necrotic cells or secreted by stimulated cells, is one of a number of ligands promoting TLR4 reactivity. Augmentation of DC numbers in the liver with GM-CSF hydrodynamic transfection significantly increased liver damage after I/R when compared with controls. TLR4 engagement on hepatic DC was required for the I/R-induced injury, as augmentation of DC numbers in TLR4 mutant (C3H/HeJ) mice did not worsen hepatic damage. It is interesting that TLR4 expression was increased in hepatic DC following HMGB1 stimulation in vitro, suggesting a mechanism for the increased liver injury following I/R. It thus appears that functional TLR4 on DC is required for I/R-induced injury. Furthermore, HMGB1 may direct the inflammatory responses mediated by DC, at least in part, by enhancing TLR4 expression and reactivity to it and other DAMPs.
Association of α2-Heremans-Schmid Glycoprotein Polymorphisms with Subclinical Atherosclerosis
Authors: Lehtinen Allison B. , Burdon Kathryn P. , Lewis Joshua P. , Langefeld Carl D. , Ziegler Julie T. , Rich Stephen S. , Register Thomas C. , Carr J. Jeffrey , Freedman Barry I. , Bowden Donald W.
Published: October 2006

Context: Cardiovascular disease is significantly increased in individuals with type 2 diabetes mellitus (T2DM), especially in the presence of calcified atherosclerotic plaque. Fetuin A is an important mineralization inhibitor, and polymorphisms in the corresponding α2-Heremans-Schmid glycoprotein (AHSG) gene have been shown to be associated with serum fetuin A levels and free phosphate levels, as well as cardiovascular disease death.

Objective: This study investigated whether polymorphisms in AHSG contribute to the development of calcified atherosclerotic plaque in the coronary and carotid arteries and to carotid artery intima-media thickness.

Design: Eleven single nucleotide polymorphisms (SNPs) in AHSG were genotyped and evaluated for association with quantitative measures of subclinical atherosclerosis.

Participants: Subjects were 829 T2DM-affected European Americans from 368 families in the Diabetes Heart Study.

Main Outcome Measures: Participants were phenotyped for cardiovascular risk factors and atherosclerosis traits. The extent of coronary artery calcified plaque (CorCP) and carotid artery calcified plaque (CarCP) was measured using quantitative computed tomography, and carotid artery intima-media thickness was measured using high-resolution B mode ultrasonography.

Results: Four SNPs in AHSG were nominally associated with CorCP in European Americans with T2DM (P < 0.05). Two 3-SNP haplotypes in the exon 6–7 region were associated with CorCP in European Americans with T2DM (P < 0.06).

Conclusions: Sequence variants in the AHSG gene affect the extent of CorCP in T2DM-affected European Americans, consistent with the known biological role of AHSG in vascular calcification. These data implicate AHSG in the development of vascular calcified plaque in diabetic subjects.
GRIF1 binds Hrs and is a new regulator of endosomal trafficking
Authors: Kirk Elizabeth , Chin Lih-Shen , Li Lian
Published: October 2006

Endosomal sorting of internalized cell surface receptors to the lysosomal pathway plays a crucial role in the control of cell signaling and function. Here we report the identification of GABAA receptor interacting factor-1 (GRIF1), a recently discovered protein of unknown function, as a new regulator of endosome-to-lysosome trafficking. Yeast two-hybrid screen and co-immunoprecipitation analysis reveal that GRIF1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), an essential component of the endosomal sorting machinery. We have mapped the binding domains of GRIF1 and Hrs that mediate their association and shown the colocalization of GRIF1 with Hrs on early endosomes. Like Hrs, both overexpression and siRNA-mediated depletion of GRIF1 inhibit the degradation of internalized epidermal growth factor receptors and block the trafficking of the receptors from early endosomes to the lysosomal pathway. Our results indicate, for the first time, a functional role for GRIF1 in the regulation of endosomal trafficking. Interestingly, overexpression of full-length GRIF1, but not the Hrs- or kinesin-interacting GRIF1 deletion mutants, causes a perinuclear clustering of early endosomes. Our findings suggest that GRIF1 may also participate in microtubule-based transport of early endosomes by acting as an adaptor linking Hrs-containing endosomes to kinesin.
Synthesis of Nanocrystalline ZnWO4 via Molten Salt Route and Its Photoluminescence
Authors: Ran Songlin , Gao Lian
Published: October 2006

ZnWO4 nanocrystalline powder has been synthesized by the molten salt route using KNO3/NaNO3 mixture as reaction media. Pure ZnWO4 phase was obtained at 250 °C for 2 h without any intermediate phase. Particle size and morphology of the powder were studied by transmission electron microscopy (TEM). The luminescent properties of the final powder as functions of the reaction temperature and time have been studied.
An Efficient and Facile Synthesis of 2-Amino-4,6-diarylbenzene-1,3-dicarbonitrile and 1,2-Dihydro-2-oxo-4,6-diarylpyridine-3-carbonitrile under Solvent-free Conditions
Authors: Rong Liangce , Li Xiaoyue , Wang Haiying , Shi Daqing , Tu Shujiang
Published: October 2006

A one-pot three-component condensation of aromatic aldehyde, aromatic ketone, and malononitrile leading to an efficient synthesis of 2-amino-4,6-diarylbenzene-1,3-dicarbonitrile and 1,2-dihydro-2-oxo-4,6-diarylpyridine-3-carbonitrile has been carried out in a mortar just by grinding or heating under solvent-free conditions. Compared with the classical reaction conditions, these new synthetic methods have the advantages of excellent yields, shorter reaction time, and mild reaction conditions.
Self-splicing of a group I intron reveals partitioning of native and misfolded RNA populations in yeast
Authors: Jackson Scott A. , Koduvayur Sujatha , Woodson Sarah A.
Published: October 2006

Stable RNAs must form specific three-dimensional structures, yet many RNAs become kinetically trapped in misfolded conformations. To understand the factors that control the accuracy of RNA folding in the cell, the self-splicing activity of the Tetrahymena group I intron was compared in different genetic contexts in budding yeast. The extent of splicing was 98% when the intron was placed in its natural rDNA context, but only 3% when the intron was expressed in an exogenous pre-mRNA. Further experiments showed that the probability of forming the active intron structure depends on local sequence context and transcription by Pol I. Pre-rRNAs decayed at similar rates, whether the intron was wild type or inactivated by an internal deletion, suggesting that most of the unreacted pre-rRNA is incompetent to splice. Northern blots and complementation assays showed that mutations that destabilize the intron tertiary structure inhibited self-splicing and processing of internal transcribed spacer 2. The data are consistent with partitioning of pre-rRNAs into active and inactive populations. The misfolded RNAs are sequestered and degraded without refolding to a significant extent. Thus, the initial fidelity of folding can dictate the intracellular fate of transcripts containing this group I intron.
Hearing results following atticotomy
Authors: Donald Paul J. , Baker Shan R.
Published: October 2006

Transmeatal atticotomy, a common otosurgical procedure near the turn of the century, has since enjoyed only sporadic periods of popularity. An earlier report illustrated the efficacy of the atticotomy operation in ablating cholesteatoma in 83% of cases. However, the ossicular chain usually suffers discontinuity either through erosion by cholesteatoma or surgical disarticulation. In ears with an intact chain, the incudostapedial joint is usually separated to avoid injury that may be transmitted to the inner ear if the rotating burr contacts the ossicles.

The purpose of this paper is to portray the types of hearing restoration attempted and the results achieved in 55 patients who had an atticotomy procedure and had been followed for six months to eight years. The number of patients who attained serviceable hearing are compared to those that did not, with regard to such factors as the hearing level and state of the ossicles preoperatively as well as the extent of the surgery required for removal of the disease.

The hearing results in these patients who underwent atticotomy compare favorably to those cited in the literature for tympanoplasties done with the modified radical mastoidectomy or the intact canal wall tympanomastoidectomy.
Removable Borehole Extensometers for Measuring Axial Displacements During Well Tests
Authors: Schweisinger T , Murdoch L , Huey C
Published: October 2006

Fractures in rock hold important stores of water and petroleum, and slight changes in fracture aperture accompanying drawdown from pumping wells play a key role in recovering these resources. Two removable borehole extensometers were designed to measure small displacements in order to improve the characterization of fractured rock aquifers using hydraulic well tests. The extensometers consist of four major components: (1) a pair of anchors, (2) a temperature-compensated reference rod, (3) a registration system, and (4) a displacement transducer. One extensometer uses an axial reference rod with multiple, low-profile anchors, whereas another uses an offset reference rod with a single pair of anchors. Both designs can be readily mobilized and are capable of resolving submicron displacements in boreholes.
Neural Mechanisms of Expert Skills in Visual Working Memory
Authors: Moore Christopher D. , Cohen Michael X. , Ranganath Charan
Published: October 2006

Expertise can increase working memory (WM) performance, but the cognitive and neural mechanisms of these improvements remain unclear. Here, we used functional magnetic resonance imaging to assess the degree to which expertise acquisition is supported by tuning of occipitotemporal object representations and tuning of prefrontal and parietal networks that may support domain-specific WM skills. We trained subjects to become experts in a novel category of complex visual objects and examined brain activity while they performed a WM task with objects from the expert category and from an untrained category. Visual expertise training resulted in improved recognition of expert, compared with untrained objects, and this effect was eliminated in a behavioral experiment by stimulus inversion. These behavioral changes were accompanied by increased recruitment of bilateral dorsolateral prefrontal, posterior parietal, and occipitotemporal cortices during WM encoding and maintenance. Across subjects, behavioral measures of expertise reliably predicted increased activation during maintenance of expert objects in all three regions. These neural expertise effects could not be attributed to differences in low-level stimulus characteristics between the two categories, familiarity with features of expert-domain objects, or familiarity with the WM task. These results are consistent with the idea that visual expertise improves WM performance through tuning of occipitotemporal object representations and through development of lateral prefrontal and posterior parietal networks that mediate the application of domain-specific mnemonic skills.
Phospholipases A2Mediate Amyloid-β Peptide-Induced Mitochondrial Dysfunction
Authors: Zhu Donghui , Lai Yinzhi , Shelat Phullara B. , Hu Chunhua , Sun Grace Y. , Lee James C-M.
Published: October 2006

Mitochondrial dysfunction has been implicated in the pathophysiology of Alzheimer's disease (AD) brains. To unravel the mechanism(s) underlying this dysfunction, we demonstrate that phospholipases A2(PLA2s), namely the cytosolic and the calcium-independent PLA2s (cPLA2and iPLA2), are key enzymes mediating oligomeric amyloid-β peptide (Aβ1–42)-induced loss of mitochondrial membrane potential and increase in production of reactive oxygen species from mitochondria in astrocytes. Whereas the action of iPLA2is immediate, the action of cPLA2requires a lag time of ∼12–15 min, probably the time needed for initiating signaling pathways for the phosphorylation and translocation of cPLA2to mitochondria. Western blot analysis indicated the ability of oligomeric Aβ1–42to increase phosphorylation of cPLA2in astrocytes through the NADPH oxidase and mitogen-activated protein kinase pathways. The involvement of PLA2in Aβ1–42-mediated perturbations of mitochondrial function provides new insights to the decline in mitochondrial function, leading to impairment in ATP production and increase in oxidative stress in AD brains.
Asphärenprüfung mit computergenerierten Hologrammen (Testing Aspheric Optics by Use of Computer-generated Holograms)
Authors: Reichelt Stephan , Tiziani Hans
Published: October 2006

Flächenhafte interferometrische Prüfverfahren sind zur Qualitätsbeurteilung optischer Bauteile prädestiniert. Die Prüfung von asphärischen optischen Flächen oder Systemen erfordert jedoch fast immer spezielle Nullkompensatoren. Für diese Aufgabe werden häufig computergenerierte Hologramme (CGHs) eingesetzt. Sie zeichnen sich dadurch aus, dass mit einer einzigen diffraktiv wirkenden Funktionsfläche eine einfallende Wellenfront nahezu beliebig manipuliert werden kann. Die speziellen Anforderungen an die Asphärenprüfung mit computergenerierten Hologrammen werden entlang des gesamten Zyklus behandelt, beginnend von der Auslegung des Prüfaufbaus über Design und Herstellung der CGHs bis hin zur Anwendung und Kalibrierung der Hologramme.
Linking Conformity Assessment and Measurement Uncertainty – an Example (Konformitätsbewertung und Messunsicherheit – eine Fallstudie)
Authors: Hinrichs Wilfried
Published: October 2006

Measurement uncertainty influences conformance assessment and hence statements on the conformity of products. An international draft guide on conformance testing and measurement uncertainty specifies for production purposes how to proceed if a quantification of this influence is needed. In this contribution the methods of this document are applied to conformity assessment. The study is based on the world-market products wire screen and woven wire cloth specified in international standards. The conclusion is that in principle the methods in the draft guide are well applicable to this group of products both for conformity and for conformance assessment. Only some provisions for the probability density of measurement results had to be changed. The overall-results are realistic when the procedures given are adapted to the specific purposes under investigation.
Ectopic ACTH syndrome: our experience with 25 cases
Authors: Salgado Luiz Roberto , Fragoso Maria Candida B Villares , Knoepfelmacher Mirta , Machado Marcio Carlos , Domenice Sorahia , Pereira Maria Adelaide Albergaria , de Mendonça Berenice Bilharinho
Published: October 2006

Objective: Ectopic ACTH syndrome (EAS) occurs in about 5–10% of all patients with ACTH-dependent hypercortisolism with most of them caused by intrathoracic neoplasms. It may be associated with overt malignancies or with occult and indolent tumors. We assessed the accuracy of dynamic tests, inferior petrosal sinus sampling (IPSS) using desmopressin, and imaging in the work-up diagnosis of EAS.

Design and subjects: Tumor markers, imaging, and outcome data from 25 patients (13F/12M) aged 18–72 years. High dexamethasone suppression test (HDDST), desmopressin test, GHRP-6 test, corticotropin-releasing hormone (CRH) test, IPSS, computed tomography (CT), magnetic resonance imaging (MRI), and 111In-pentetreotide scintigraphy were revised.

Results: In 5 out of 20 patients HDDST was positive. In 13 patients who underwent desmopressin test, ACTH- and cortisol-positive responses were seen in six and five patients respectively. GHRP-6 test was positive in two out of three cases. Two patients underwent CRH test with negative response. In the seven patients submitted to IPSS using desmopressin in six of them, none had ACTH gradients. CT was positive in 15 out of 21 patients and MRI in 8 out of 17 cases. 111In-pentetreotide scintigraphy was positive in three out of five patients. Fourteen patients had intrathoracic tumors, five had pheochromocytomas, three had pancreatic tumors, one had a glomic tumor, and had three occult tumors. Six out of 11 patients with metastasis died and 3 others without metastasis died.

Conclusions: IPSS with desmopressin was helpful for differential diagnosis. Patients initially harboring occult carcinoids may also exhibit severe hypercortisolism and those harboring tymic carcinoids had poor prognoses when compared with bronchial carcinoids and pheocromocytomas.