bluuebunny/crossref_metadata_2025 huggingface dataset:
MDM2 SNP309 and SNP354 Are Not Associated with Lung Cancer Risk
Authors: Pine Sharon R. , Mechanic Leah E. , Bowman Elise D. , Welsh Judith A. , Chanock Stephen C. , Shields Peter G. , Harris Curtis C.
Published: August 2006

A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been found to be associated with tumor formation. Publication of this null report is important because an association between MDM2 SNP309 and lung cancer was previously reported in two independent studies. Our findings suggest that MDM2 SNP309 is not a strong factor in lung carcinogenesis. In addition, this is the first MDM2 SNP309 report on a population consisting of Caucasians in the United States and African-Americans. A strength of the study design is that the controls consist of both population and hospital controls. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1559–61)
The Prevalence of CDKN2A Germ-Line Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study
Authors: Berwick Marianne , Orlow Irene , Hummer Amanda J. , Armstrong Bruce K. , Kricker Anne , Marrett Loraine D. , Millikan Robert C. , Gruber Stephen B. , Anton-Culver Hoda , Zanetti Roberto , Gallagher Richard P. , Dwyer Terence , Rebbeck Timothy R. , Kanetsky Peter A. , Busam Klaus , From Lynn , Mujumdar Urvi , Wilcox Homer , Begg Colin B. ,   The GEM Study Group
Published: August 2006

Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which “cases” have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and “controls” have incident first primary melanoma [single primary melanoma (SPM)]. Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma. (Cancer Epidemiol Biomarkers Prev 2006;15(8)1520–5)
An Interlocker Concept of Carcinogenesis
Authors: Wattenberg Lee W.
Published: August 2006

A critical feature in the sequence of events occurring during carcinogenesis is the development of irreversibility. The term “Interlocker” is used here to denote a mechanism by which irreversibility is brought about. The presentation focuses on conceptualizations of such processes. Two will be described below. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1425–6)
Superoxide Stimulates NaCl Absorption in the Thick Ascending Limb Via Activation of Protein Kinase C
Authors: Silva Guillermo B. , Ortiz Pablo A. , Hong Nancy J. , Garvin Jeffrey L.
Published: August 2006

Abnormal production of superoxide (O
2
−
) contributes to hypertension, in part because of its effects on the kidney. The thick ascending limb absorbs 20% to 30% of the filtered load of NaCl. O
2
−
stimulates NaCl absorption by the thick ascending limb by enhancing Na
+
/K
+
/2Cl
−
cotransporter activity; however, the signaling mechanism is unknown. We hypothesized that O
2
−
stimulates NaCl absorption by activating protein kinase C (PKC). To test this, we measured the effect of O
2
−
on: (1) Cl
−
absorption in the presence and absence of PKC inhibitors, (2) total PKC activity, and (3) activation of specific PKC isoforms. Isolated perfused medullary thick ascending limbs were exposed to O
2
−
generated by xanthine oxidase (1 mU/mL) and hypoxanthine (0.5 mmol/L). O
2
−
increased Cl
−
absorption by 42% (from 76.2±3.6 to 108.2±11.9 pmol/min per millimeter; n=5;
P
<0.05). After treatment with the general PKC inhibitor staurosporine (10 nmol/L), O
2
−
did not stimulate Cl
−
absorption (Δ−5.7±8.6%; n=6). In thick ascending limb suspensions, O
2
−
increased total PKC activity by 33% (from 66±11 to 88±12 mU/mg protein; n=5
; P
<0.05) and increased PKC-α and PKC-δ activity by 1.75- and 0.37-fold, respectively. The PKC-α/β–selective inhibitor Gö976 (100 nmol/L) blocked the ability of O
2
−
to stimulate Cl
−
absorption by isolated perfused medullary thick ascending limbs (Δ4.5±15.0%; n=5). The role of PKC-δ could not be studied because of cell necrosis caused by the selective inhibitor rottlerin. We conclude that PKC-α is required for O
2
−
-stimulated NaCl absorption in the thick ascending limb.
Apolipoprotein CIII Induces Expression of Vascular Cell Adhesion Molecule-1 in Vascular Endothelial Cells and Increases Adhesion of Monocytic Cells
Authors: Kawakami Akio , Aikawa Masanori , Alcaide Pilar , Luscinskas Francis W. , Libby Peter , Sacks Frank M.
Published: August 2006

Background—

Activation of vascular endothelial cells (ECs) plays an important role in atherogenesis and plaque instability. Lipoproteins containing apolipoprotein CIII (apoCIII) predict coronary heart disease (CHD). We recently reported that apoCIII has a proinflammatory effect on human monocytes. In this study, we looked for a direct effect of apoCIII on EC expression of adhesion molecules, leading to monocytic cell adhesion.

Methods and Results—

Treatment of ECs with apoCIII or apoCIII-rich VLDL caused human monocytic THP-1 cells to adhere to them under static condition or under laminar sheer stress (1.0 dyne/cm
2
). ApoCIII increased EC expression of vascular cell adhesion molecule-1 (VCAM-1) protein and intercellular cell adhesion molecule-1 (ICAM-1) protein (4.9±1.5-fold and 1.4±0.5-fold versus control, respectively). Furthermore, apoCIII remarkably increased membrane-bound protein kinase C (PKC) β in ECs, indicating activation. A selective inhibitor of PKCβ prevented the rise in VCAM-1 and THP-1 cell adhesion to ECs. Moreover, exposure of ECs to apoCIII induced nuclear factor-κB (NF-κB) activation. PKCβ inhibition abolished apoCIII-induced NF-κB activation, and NF-κB inhibition reduced expression of VCAM-1, each resulting in reduced THP-1 cell adhesion. ApoCIII-rich VLDL also activated PKCβ and NF-κB in ECs and increased expression of VCAM-1. Pretreatment of ApoCIII-rich VLDL with anti-apoCIII neutralizing antibody abolished its effect on PKCβ activation.

Conclusions—

Our findings provide the first evidence that apoCIII increases VCAM-1 and ICAM-1 expression in ECs by activating PKCβ and NF-κB, suggesting a novel mechanism for EC activation induced by dyslipidemia. Therefore, apoCIII-rich VLDL may contribute directly to atherogenesis by activating ECs and recruiting monocytes to them.
Local Controlled Intramyocardial Delivery of Platelet-Derived Growth Factor Improves Postinfarction Ventricular Function Without Pulmonary Toxicity
Authors: Hsieh Patrick C.H. , MacGillivray Catherine , Gannon; Joseph , Cruz Francisco U. , Lee Richard T.
Published: August 2006

Background—

Local delivery methods can target therapies to specific tissues and potentially avoid toxicity to other organs. Platelet-derived growth factor can protect the myocardium, but it also plays an important role in promoting pulmonary hypertension. It is not known whether local myocardial delivery of platelet-derived growth factor during myocardial infarction (MI) can lead to sustained cardiac benefit without causing pulmonary hypertension.

Methods and Results—

We performed a randomized and blinded experiment of 127 rats that survived experimental MI or sham surgery. We delivered platelet-derived growth factor (PDGF)-BB with self-assembling peptide nanofibers (NFs) to provide controlled release within the myocardium. There were 6 groups with n≥20 in each group: sham, sham+NF, sham+NF/PDGF, MI, MI+NF, and MI+NF/PDGF. Serial echocardiography from 1 day to 3 months showed significant improvement of ventricular fractional shortening, end-systolic dimension, and end-diastolic dimension with local PDGF delivery (
P
<0.05 for MI+NF/PDGF versus MI or MI+NF). Catheterization at 4 months revealed improved ventricular function in the controlled delivery group (left ventricular end-diastolic pressure, cardiac index, +dP/dt, −dP/dt, and time constant of exponential decay all
P
<0.05 for MI+NF/P versus MI or MI+NF). Infarcted myocardial volume was reduced by NF/PDGF therapy (34.0±13.3% in MI, 28.9±12.9% in MI+NF, and 12.0±5.8% in MI+NF/PDGF;
P
<0.001). There was no evidence of pulmonary toxicity from the therapy, with no differences in right ventricular end-systolic pressure, right ventricular dP/dt, bromodeoxyuridine staining, or pulmonary artery medial wall thickness.

Conclusions—

Intramyocardial delivery of PDGF by self-assembling peptide NFs leads to long-term improvement in cardiac performance after experimental infarction without apparent pulmonary toxicity. Local myocardial protection may allow prevention of heart failure without systemic toxicity.
Crossing Borders: International Migration and National Security
Authors: Adamson Fiona B.
Published: August 2006

International migration has moved to the top of the international security agenda, due in part to concerns that migration flows provide conduits for the spread of international terrorism. Although such concerns are not entirely unfounded, they must be placed within the broader context of the range of impacts—both positive and negative—that international migration flows have on states' core national security interests. Migration flows affect at least three dimensions of national security: state capacity and autonomy, the balance of power, and the nature of violent conflict. Overall, migration management presents a far greater security challenge to weak and failing states than to advanced postindustrial states. States that are able to formulate and implement migration policies that harness the power of international migration will be more secure, rather than less secure, in the new globalized security environment.
The Strategies of Terrorism
Authors: Kydd Andrew H. , Walter Barbara F.
Published: August 2006

Terrorism is designed to change minds by destroying bodies; it is a form of costly signaling. Terrorists employ five primary strategies of costly signaling: attrition, intimidation, provocation, spoiling, and outbidding. The main targets of persuasion are the enemy and the population that the terrorists hope to represent or control. Terrorists wish to signal that they have the strength and will to impose costs on those who oppose them, and that the enemy and moderate groups on the terrorists' side cannot be trusted and should not be supported. Each strategy works well under certain conditions and poorly under others. State responses to one strategy may be inappropriate for other strategies. In some cases, however, terrorists are pursuing a combination of strategies, and the response must also work well against this combination.
Fostering Stability or Creating a Monster? The Rise of China and U.S. Policy toward East Asia
Authors: Christensen Thomas J.
Published: August 2006

This article explores two starkly contrasting analytic approaches to assessing the performance of U.S. security strategy in East Asia since 1991: a positivesum approach, emphasizing the danger of security dilemmas and spirals of tension, and a zero-sum approach, emphasizing power competition and the long-term dangers posed by China's rise. In the policy world, the differences between these apparently irreconcilable perspectives are not so clear. Certain policies—for example, maintaining a strong U.S.-Japan alliance—flow from either logic. Moreover, each approach sometimes counsels counterintuitive policy prescriptions that are generally associated with the other. Relatively assertive U.S. security postures apparently have furthered positive-sum regional goals by catalyzing China to adopt reassuring policies toward its neighbors as a hedge against potential U.S. encirclement. From a zero-sum perspective, the United States often competes more effectively for regional influence by cooperating with China than it would by seeking to contain China's economic growth and diplomatic influence.
Co-Occurring Mental Illness and Substance Abuse in the Criminal Justice System
Authors: White Michael D. , Goldkamp John S. , Campbell Suzanne P.
Published: August 2006

The increasing role of police, courts, and corrections in dealing with the mentally ill represents a significant challenge facing local justice systems. This article considers the impact of mentally ill and substance-abusing offenders in Santa Fe, New Mexico, by comparing a random sample of individuals detained on protective custody and mental health holds ( n = 338) to a random sample of defendants arrested on criminal charges ( n = 153). Results indicate that police encounter individuals with co-occurring disorders on a daily basis and that individuals detained on holds are much more likely than are those arrested to generate additional police contacts during a 1-year follow-up period. Individuals with co-occurring disorders also represent a serious financial burden on the local system, particularly in terms of confinement costs. The article concludes with a discussion of implications for criminal justice policy and practice.
Aggression Levels Among Correctional Officers
Authors: Tewksbury Richard , Collins Sue Carter
Published: August 2006

Questions about the abilities and appropriateness of female correctional officers working in adult men’s correctional institutions have been asked since women first entered men’s prisons. Although some scholars argue that women should not, or cannot, work effectively in such settings, others have shown that there are few differences in quality of work or productivity. Building on this line of research, the present study assesses self-reported perceptions of differences in aggressive responses to instances of inmate challenges and misbehavior. Findings indicate that there are no differences in men’s and women’s responses, and only three variables (job title, height, and having minor children) predict any differences in staff responses. In addition, although female correctional officers report a higher degree of job-related stress than do males, job stress is not related to likelihood of aggressive responses. Findings are discussed in relation to historical and contextual differences between the present study and previous research.
Controlling a Jail Population by Partially Closing the Front Door
Authors: Baumer Terry L. , Adams Kenneth
Published: August 2006

This study reports on an evaluation of a strategy designed to reduce crowding of a county jail. The local judiciary sought to reduce the jail population by ordering local police agencies to issue a summons rather than arrest individuals accused of seven misdemeanor offenses. The study compares all cases booked during the first 8 months of the policy with all cases booked during the same months in the previous year. The results indicate that the policy was implemented, that it did reduce the intake population, and that there were minimal side effects; however, the potential impact was considerably overestimated in the planning stage.
“We Always Have a Beer after the Meeting”
Authors: Jones Todd
Published: August 2006

There are a vast number of ways of explaining human behavior in the social sciences and in ordinary conversation. One family of accounts seeks to explain behavior using terms such as norms, customs, tradition, convention, and culture. Despite the ubiquity of these terms, it is not fully clear how these concepts really explain behavior, how they are related, how they differ, and what they contrast with. In this article, I hope to answer such questions.
Boas and Holism
Authors: Verdon Michel
Published: August 2006

Some anthropologists advocate going back to Boas’s anthropology to retrieve his sense of the individual and agency, among other things. Such a “psycho-logical Boas” could only exist in his holistic works. Elsewhere, I argued in a very synthetic way that Boas’s ethnography was not holistic. Here, I move a step further; perusing the very texts that famous commentators have singled out to prove Boas’s holism, I discover no holism; I find history as mere movement in space, and no individual agents; hence, no real psychology or agency. I only discern cultural fragments randomly assembling to form regional cultures.
Toward Pragmatist Methodological Relationalism
Authors: Kivinen Osmo , Piiroinen Tero
Published: August 2006

In this article, relationalist approaches to social sciences are analyzed in terms of a conceptual distinction between “philosophizing sociology” and “sociologizing philosophy.” These mark two different attitudes toward philosophical metaphysics and ontological commitments. The authors’ own pragmatist methodological relationalism of Deweyan origin is compared with ontologically committed realist approaches, as well as with Bourdieuan methodological relationalism. It is argued that pragmatist philosophy of social sciences is an appropriate tool for assisting social scientists in their methodological work, especially as regards problem-driven case studies.
Review Essay: The Philosophical Buck Stops Here
Authors: Fuller Steve
Published: August 2006

George Reisch documents how the logical positivists adapted to their émigré status in the United States by relinquishing their leftist political ambitions and turning into the analytic philosophy establishment that persists to this day. However, there are also deep-seated tendencies in US intellectual history that provide reasons for thinking that the positivists’ progressive projects would never have taken hold—even if the FBI were not keeping the positivists under surveillance. These tendencies are manifested in the striking ineffectuality of US philosophers in public life.
Review Essay: High-Heeled Red Imitation-Crocodile Boots
Authors: King Anthony
Published: August 2006

The two works under review attempt to describe the outlines of a post-positivist social science of the future. Against objectivist approaches, these books emphasize the importance of hermeneutics and the cultural turn to the social sciences. Social sciences must recognize collective understandings and human agency. However, while affirming the importance of an interpretivist approach, both of these works also suggest that objective institutional reality must be recognized by social scientists today. Meaningful human agency and objective structure must be encompassed by the social sciences. To this end, critical realism, originally promoted by Roy Bhaskar, figures prominently in both these books precisely because it is a theory which seems to be able to account for both agency and structure simultaneously. In fact, as both these books sometimes demonstrate, the dualistic approach represented by critical realism is flawed. By contrast, the hermeneutic approach advocated by Keith Topper and by some of the contributors to Steinmetz’s collection provides an adequate explanation of institutional social reality in and of itself. Consequently, these books can be interpreted as pointing toward a hermeneutic social science of the future.
Prognostic significance of CD20 expression in childhood B-cell precursor acute lymphoblastic leukemia
Authors: Jeha Sima , Behm Frederick , Pei Deqing , Sandlund John T. , Ribeiro Raul C. , Razzouk Bassem I. , Rubnitz Jeffrey E. , Hijiya Nobuko , Howard Scott C. , Cheng Cheng , Pui Ching-Hon
Published: August 2006

CD20 expression is associated with inferior survival in adults with acute lymphoblastic leukemia (ALL). We analyzed the prognostic impact of CD20 expression in 353 children with B-cell precursor ALL treated in 3 consecutive St Jude Total Therapy studies. CD20 expression (> 20%) was found in 169 patients (48%) and was more frequent in patients between 1 and 10 years of age than in those younger than 1 or older than 10 years (P = .001). None of 14 patients with MLL-AF4 expressed CD20. There was no association between CD20 expression and E2A-PBX, TEL-AML1, ploidy, white blood cell count at diagnosis, or sex. In contrast to the experience in adult ALL, our patients with CD20 expression tended to have a better treatment outcome than those without the expression: 5-year event-free survival 84% ± 2.9% versus 78% ± 3.1% (P = .08). These data suggest that CD20 expression is not associated with inferior outcome in pediatric patients treated with contemporary regimens.
Reference values for exhaled nitric oxide (reveno) study
Authors: Olivieri Mario , Talamini Giorgio , Corradi Massimo , Perbellini Luigi , Mutti Antonio , Tantucci Claudio , Malerba Mario
Published: August 2006

Background

Despite the widespread use of fractional exhaled nitric oxide (FENO) as a biomarker of airways inflammation, there are no published papers describing normal FENO values in a large group of healthy adults.

Objective

The aim of this study was to establish adult FENO reference values according to the international guidelines.

Methods

FENO was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently.

Results

The main result of the study was the significant difference in FENO values between men and women, thus indicating that gender-based reference FENO values are necessary. The FENO levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women.

Conclusion

We propose reference FENO values for healthy adult men and women that could be used for clinical and research purposes.
Contributions of differential p53 expression in the spontaneous immortalization of a chicken embryo fibroblast cell line
Authors: Christman Shelly A , Kong Byung-Whi , Landry Megan M , Kim Hyunggee , Foster Douglas N
Published: August 2006

Background

The present study was carried out to determine whether the p53 pathway played a role in the spontaneous immortalization of the SC-2 chicken embryo fibroblast (CEF) cell line that has been in continuous culture for over three years.

Results

The SC-2 cell line emerged from an extended crisis period with a considerably slower growth rate than primary CEF cells. The phenotype of the SC-2 cells changed dramatically at about passage 80, appearing smaller than at earlier passages (e.g., passage 43) and possessing a small, compact morphology. This morphological change coincided with an increase in growth rate. Passage 43 SC-2 cells expressed undetectable levels of p53 mRNA, but by passage 95, the levels were elevated compared to primary passage 6 CEF cells and similar to levels in senescent CEF cells. However, the high level of p53 mRNA detected in passage 95 SC-2 cells did not correlate to functional protein activity. The expression levels of the p53-regulated p21WAF1 gene were significantly decreased in all SC-2 passages that were analyzed. Examination of the Rb pathway revealed that E2F-1 and p15INK4b expression fluctuated with increasing passages, with levels higher in passage 95 SC-2 cells compared to primary passage 6 CEF cells.

Conclusion

The present study suggests that altered expression of genes involved in the p53 and Rb pathways, specifically, p53 and p21WAF1, may have contributed to the immortalization of the SC-2 CEF cell line.
TBLR1 regulates the expression of nuclear hormone receptor co-repressors
Authors: Zhang Xin-Min , Chang Qing , Zeng Lin , Gu Judy , Brown Stuart , Basch Ross S
Published: August 2006

Background

Transcription is regulated by a complex interaction of activators and repressors. The effectors of repression are large multimeric complexes which contain both the repressor proteins that bind to transcription factors and a number of co-repressors that actually mediate transcriptional silencing either by inhibiting the basal transcription machinery or by recruiting chromatin-modifying enzymes.

Results

TBLR1 [GenBank: NM024665] is a co-repressor of nuclear hormone transcription factors. A single highly conserved gene encodes a small family of protein molecules. Different isoforms are produced by differential exon utilization. Although the ORF of the predominant form contains only 1545 bp, the human gene occupies ~200 kb of genomic DNA on chromosome 3q and contains 16 exons. The genomic sequence overlaps with the putative DC42 [GenBank: NM030921] locus. The murine homologue is structurally similar and is also located on Chromosome 3. TBLR1 is closely related (79% homology at the mRNA level) to TBL1X and TBL1Y, which are located on Chromosomes X and Y. The expression of TBLR1 overlaps but is distinct from that of TBL1. An alternatively spliced form of TBLR1 has been demonstrated in human material and it too has an unique pattern of expression. TBLR1 and the homologous genes interact with proteins that regulate the nuclear hormone receptor family of transcription factors. In resting cells TBLR1 is primarily cytoplasmic but after perturbation the protein translocates to the nucleus. TBLR1 co-precipitates with SMRT, a co-repressor of nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by antiserum to HDAC3. Cells engineered to over express either TBLR1 or N- and C-terminal deletion variants, have elevated levels of endogenous N-CoR. Co-transfection of TBLR1 and SMRT results in increased expression of SMRT. This co-repressor undergoes ubiquitin-mediated degradation and we suggest that the stabilization of the co-repressors by TBLR1 occurs because of a novel mechanism that protects them from degradation. Transient over expression of TBLR1 produces growth arrest.

Conclusion

TBLR1 is a multifunctional co-repressor of transcription. The structure of this family of molecules is highly conserved and closely related co-repressors have been found in all eukaryotic organisms. Regulation of co-repressor expression and the consequent alterations in transcriptional silencing play an important role in the regulation of differentiation.
Integration of hybridization-based markers (overgos) into physical maps for comparative and evolutionary explorations in the genus Oryza and in Sorghum
Authors: Hass-Jacobus Barbara L , Futrell-Griggs Montona , Abernathy Brian , Westerman Rick , Goicoechea Jose-Luis , Stein Joshua , Klein Patricia , Hurwitz Bonnie , Zhou Bin , Rakhshan Fariborz , Sanyal Abhijit , Gill Navdeep , Lin Jer-Young , Walling Jason G , Luo Mei Zhong , Ammiraju Jetty Siva S , Kudrna Dave , Kim Hye Ran , Ware Doreen , Wing Rod A , Miguel Phillip San , Jackson Scott A
Published: August 2006

Background

With the completion of the genome sequence for rice (Oryza sativa L.), the focus of rice genomics research has shifted to the comparison of the rice genome with genomes of other species for gene cloning, breeding, and evolutionary studies. The genus Oryza includes 23 species that shared a common ancestor 8–10 million years ago making this an ideal model for investigations into the processes underlying domestication, as many of the Oryza species are still undergoing domestication. This study integrates high-throughput, hybridization-based markers with BAC end sequence and fingerprint data to construct physical maps of rice chromosome 1 orthologues in two wild Oryza species. Similar studies were undertaken in Sorghum bicolor, a species which diverged from cultivated rice 40–50 million years ago.

Results

Overgo markers, in conjunction with fingerprint and BAC end sequence data, were used to build sequence-ready BAC contigs for two wild Oryza species. The markers drove contig merges to construct physical maps syntenic to rice chromosome 1 in the wild species and provided evidence for at least one rearrangement on chromosome 1 of the O. sativa versus Oryza officinalis comparative map. When rice overgos were aligned to available S. bicolor sequence, 29% of the overgos aligned with three or fewer mismatches; of these, 41% gave positive hybridization signals. Overgo hybridization patterns supported colinearity of loci in regions of sorghum chromosome 3 and rice chromosome 1 and suggested that a possible genomic inversion occurred in this syntenic region in one of the two genomes after the divergence of S. bicolor and O. sativa.

Conclusion

The results of this study emphasize the importance of identifying conserved sequences in the reference sequence when designing overgo probes in order for those probes to hybridize successfully in distantly related species. As interspecific markers, overgos can be used successfully to construct physical maps in species which diverged less than 8 million years ago, and can be used in a more limited fashion to examine colinearity among species which diverged as much as 40 million years ago. Additionally, overgos are able to provide evidence of genomic rearrangements in comparative physical mapping studies.
Bloodstream infection following 217 consecutive systemic-enteric drained pancreas transplants
Authors: Berger Natalie , Guggenbichler Sigmund , Steurer Wolfgang , Margreiter Christian , Mayer Gert , Kafka Reinhold , Mark Walter , Rosenkranz Alexander R , Margreiter Raimund , Bonatti Hugo
Published: August 2006

Background

Combined kidney pancreas transplantation (PTx) evolved as excellent treatment for diabetic nephropathy. Infections remain common and serious complications.

Methods

217 consecutive enteric drained PTxs performed from 1997 to 2004 were retrospectively analyzed with regard to bloodstream infection. Immunosuppression consisted of antithymocyteglobuline induction, tacrolimus, mycophenolic acid and steroids for the majority of cases. Standard perioperative antimicrobial prophylaxis consisted of pipercillin/tazobactam in combination with ciprofloxacin and fluconazole.

Results

One year patient, pancreas and kidney graft survival were 96.4%, 88.5% and 94.8%, surgical complication rate was 35%, rejection rate 30% and rate of infection 59%. In total 46 sepsis episodes were diagnosed in 35 patients (16%) with a median onset on day 12 (range 1–45) post transplant. Sepsis source was intraabdominal infection (IAI) (n = 21), a contaminated central venous line (n = 10), wound infection (n = 5), urinary tract infection (n = 2) and graft transmitted (n = 2). Nine patients (4%) experienced multiple episodes of sepsis. Overall 65 pathogens (IAI sepsis 39, line sepsis 15, others 11) were isolated from blood. Gram positive cocci accounted for 50 isolates (77%): Coagulase negative staphylococci (n = 28, i.e. 43%) (nine multi-resistant), Staphylococcus aureus (n = 11, i.e. 17%) (four multi-resistant), enterococci (n = 9, i.e. 14%) (one E. faecium). Gram negative rods were cultured in twelve cases (18%). Patients with blood borne infection had a two year pancreas graft survival of 76.5% versus 89.4% for those without sepsis (p = 0.036), patient survival was not affected.

Conclusion

Sepsis remains a serious complication after PTx with significantly reduced pancreas graft, but not patient survival. The most common source is IAI.
Mutations in PIK3CAare infrequent in neuroblastoma
Authors: Dam Vincent , Morgan Brian T , Mazanek Pavel , Hogarty Michael D
Published: August 2006

Background

Neuroblastoma is a frequently lethal pediatric cancer in which MYCN genomic amplification is highly correlated with aggressive disease. Deregulated MYC genes require co-operative lesions to foster tumourigenesis and both direct and indirect evidence support activated Ras signaling for this purpose in many cancers. Yet Ras genes and Braf, while often activated in cancer cells, are infrequent targets for activation in neuroblastoma. Recently, the Ras effector PIK3CA was shown to be activated in diverse human cancers. We therefore assessed PIK3CA for mutation in human neuroblastomas, as well as in neuroblastomas arising in transgenic mice with MYCN overexpressed in neural-crest tissues. In this murine model we additionally surveyed for Ras family and Braf mutations as these have not been previously reported.

Methods

Sixty-nine human neuroblastomas (42 primary tumors and 27 cell lines) were sequenced for PIK3CA activating mutations within the C2, helical and kinase domain "hot spots" where 80% of mutations cluster. Constitutional DNA was sequenced in cases with confirmed alterations to assess for germline or somatic acquisition. Additionally, Ras family members (Hras1, Kras2 and Nras) and the downstream effectors Pik3ca and Braf, were sequenced from twenty-five neuroblastomas arising in neuroblastoma-prone transgenic mice.

Results

We identified mutations in the PIK3CA gene in 2 of 69 human neuroblastomas (2.9%). Neither mutation (R524M and E982D) has been studied to date for effects on lipid kinase activity. Though both occurred in tumors with MYCN amplification the overall rate of PIK3CA mutations in MYCN amplified and single-copy tumors did not differ appreciably (2 of 31 versus 0 of 38, respectively). Further, no activating mutations were identified in a survey of Ras signal transduction genes (including Hras1, Kras2, Nras, Pik3ca, or Braf genes) in twenty-five neuroblastic tumors arising in the MYCN-initiated transgenic mouse model.

Conclusion

These data suggest that activating mutations in the Ras/Raf-MAPK/PI3K signaling cascades occur infrequently in neuroblastoma. Further, despite compelling evidence for MYC and RAS cooperation in vitro and in vivo to promote tumourigenesis, activation of RAS signal transduction does not constitute a preferred secondary pathway in neuroblastomas with MYCN deregulation in either human tumors or murine models.
Development and testing of innovative patient resources for the management of coronary heart disease (CHD): a descriptive study
Authors: Redfern Julie , Ellis Elizabeth , Briffa Tom , Freedman Saul B
Published: August 2006

Background

Although heart disease is a major cause of morbidity and mortality the majority of patients do not access existing rehabilitation programs and patient resources are not designed to facilitate patient choice and decision-making. The objective of this study was to develop and test a series of risk factor modules and corresponding patient information leaflets for secondary prevention of CHD.

Methods

In phase one, a series of risk factor modules and management options were developed following analysis of literature and interviews with health professionals. In phase two, module information leaflets were developed using published guidelines and interviews of people with CHD. In phase three, the leaflets were tested for quality (DISCERN), readability (Flesch) and suitability (SAM) and were compared to the existing cardiac rehabilitation (CR) information leaflet. Finally, the patients assessed the leaflets for content and relevance.

Results

Four key risk factors identified were cholesterol, blood pressure, smoking and physical inactivity. Choice management options were selected for each risk factor and included medical consultation, intensive health professional led program, home program and self direction. Patient information needs were then identified and leaflets were developed. DISCERN quality scores were high for cholesterol (62/80), blood pressure (59/80), smoking (62/80) and physical activity (62/80), all scoring 4/5 for overall rating. The mean Flesch readability score was 75, representing "fairly easy to read", all leaflets scored in the superior category for suitability and were reported to be easy to understand, useful and motivating by persons with CHD risk factors. The developed leaflets scored higher on each assessment than the existing CR leaflets.

Conclusion

Using a progressive three phase approach, a series of risk factor modules and information leaflets were successfully developed and tested. The leaflets will contribute to shared-decision making and empowerment for persons with CHD.
Exposure of hairdressing apprentices to airborne hazardous substances
Authors: Mounier-Geyssant Estelle , Oury Véronique , Mouchot Lory , Paris Christophe , Zmirou-Navier Denis
Published: August 2006

Background

Few studies have investigated exposure of hairdressing apprentices to airborne irritants. This study describes exposure levels of apprentices to chemical products used in hairdressing salons in relation with their activity.

Methods

Following a two stages study design, a group of 300 students completed a questionnaire on their work activities and environment. Among these, a group of 28 subjects volunteered to undergo personal exposure and workplace concentrations measurements over a work shift, during a cold and a hot season, with the agreement of the salon owners. Three chemical substances were studied (ammonia, hydrogen peroxide and persulfates) because they are respiratory tract irritants and because their concentrations could be quantified within a 5 to 8 hour shift period.

Results

Personal exposure values for H2O2and NH3 (averages [standard deviations] are 0.05 [0.04] and 0.90 [0.76] mg.m-3, respectively) were greater than workplace ambient air concentrations (corresponding values of 0.04 [0.03] and 0.68 [0.42] mg.m-3) for H2O2 and NH3, with no significant seasonal variation. By contrast, workplace concentrations of persulfates (0.019 [0.018] mg.m-3) were greater than personal exposure (0.016 [0.021] mg.m-3, a finding that is consistent with the fact that bleaching is more often undertaken by senior hairdressers. However, all exposure values were lower than the current TLV TWA values. This study also shows that over half of technical spaces where chemical substances used for dying, permanenting or bleaching are manipulated, have no ventilation system, and not even a door or a window opening outside.

Conclusion

The study hairdressing salons, on average, were small, the most probable reason why occupational hygiene measures such as appropriate ventilation were too seldom implemented. As a consequence, young apprentices and senior hairdressers experience substantial exposure to known airways irritants.
Evaluation of the sensitization rates and identification of IgE-binding components in wild and genetically modified potatoes in patients with allergic disorders
Authors: Lee Soo-Keol , Ye Young-Min , Yoon Sung-Ho , Lee Bou-Oung , Kim Seung-Hyun , Park Hae-Sim
Published: August 2006

Background

The potato is one of the most common types of genetically modified (GM) food. However, there are no published data evaluating the impact of genetic manipulations on the allergenicity of GM potatoes. To compare the allergenicity of GM potatoes with that of wild-type potatoes using in vivo and in vitro methods in adult allergy patients sensitized to potatoes.

Methods

A total of 1886 patients with various allergic diseases and 38 healthy controls participated in the study. Skin-prick testing and IgE-ELISA were carried out with extracts prepared from wild-type and GM potatoes. An ELISA inhibition test was used to confirm the binding specificity. IgE-binding components in extracts from the two types of potato were identified by SDS-PAGE and IgE-immunoblotting. The effects of digestive enzymes and heat on the allergenicity of the extracts was evaluated by preincubating the potatoes with or without simulated gastric and intestinal fluids in the absence or presence of heat.

Results

Positive responses (ratio of the wheal size induced by the allergen to that induced by histamine (A/H) ≥ 2+) to wild-type or GM potato extracts, as demonstrated by the skin-prick test, were observed in 108 patients (5.7%). Serum-specific IgE was detected in 0–88% of subjects who tested positively. ELISA inhibition tests indicated significant inhibition when extract from each type of potato was added. IgE-immunoblot analysis demonstrated the presence of 14 IgE-binding components within the wild-type potato and 9 within the GM potato. Furthermore, a common 45-kDa binding component that yielded similar IgE-binding patterns was noted in more than 80% of the reactions using sera from patients sensitized to wild-type or GM potato. Exposure to simulated gastric fluid and heat treatment similarly inhibited IgE binding by extracts from wild-type and GM potatoes, whereas minimal changes were obtained following exposure of the extracts to simulated intestinal fluid.

Conclusion

Our results strongly suggest that genetic manipulation of potatoes does not increase their allergenic risk. The sensitization rate of adult allergy patients to both types of extract was 5.7%, and a common major allergen (45 kDa) was identified.
Validation of an English version of the Child-OIDP index, an oral health-related quality of life measure for children
Authors: Yusuf Huda , Gherunpong Sudaduang , Sheiham Aubrey , Tsakos Georgios
Published: August 2006

Background

To evaluate the psychometric properties of the Child-OIDP for use among children in the UK and report on the prevalence of oral impacts in a sample of schoolchildren in Westminster.

Methods

Children aged 10–11 years in the final year of primary school (year 6) were selected from seven schools where annual screenings are carried out. A total of 228 children participated (99% response rate). A clinical examination was conducted followed by a questionnaire designed to measure oral health-related quality of life in children, namely the Child-OIDP. The psychometric properties of the Child-OIDP were evaluated in terms of face, content and concurrent validity in addition to internal and test-retest reliability.

Results

The Child-OIDP revealed excellent validity and good reliability. Weighted Kappa was 0.82. Cronbach's alpha coefficient was 0.58. The index showed significant associations with perceived oral treatment needs and perceived satisfaction with mouth and oral health status (p < 0.001).

Conclusion

This study has demonstrated that the Child-OIDP is a valid and reliable index to be used among 10–11 year old schoolchildren in the UK.
Burden of premature mortality in rural Vietnam from 1999 – 2003: analyses from a Demographic Surveillance Site
Authors: Huong Dao Lan , Minh Hoang Van , Vos Theo , Janlert Urban , Van Do Duc , Byass Peter
Published: August 2006

Background

Assessing the burden of disease contributes towards evidence-based allocation of limited health resources. However, such measures are not yet commonly available in Vietnam. Taking advantage of the FilaBavi Demographic Surveillance Site (FilaBavi DSS) in Vietnam, this study aimed to establish the feasibility of applying the Years of Life Lost (YLL) technique in the context of a defined DSS, and to estimate the importance of the principal causes of premature mortality in a rural area of Vietnam between 1999 and 2003.

Methods

Global Burden of Disease methods were applied. Causes of death were ascertained by verbal autopsy.

Results

In five years, 1,240 deaths occurred and for 1,220 cases cause of death information from verbal autopsy was available. Life expectancy at birth was 71.0 (95% confidence interval 69.9–72.1) in males and 80.9 (79.9–81.9) in females. The discounted, but not age weighted YLL per 1,000 population was 85 and 55 for males and females, respectively. The leading causes of YLL and death counts were cardiovascular diseases, malignant neoplasms, unintentional injuries, and neonatal causes. Males contributed 54% of total deaths and 59% of YLL. Males experienced higher YLL than women across all causes. Filabavi mortality estimates are considerably lower than 2002 WHO country estimates for Vietnam. Also the FilaBavi cause distribution varies considerably from the WHO result.

Conclusion

The combination of localised demographic surveillance, verbal autopsy and the application of YLL methods enable new insights into the magnitude and importance of significant public health issues in settings where evidence for planning is otherwise scarce. Local mortality data vary considerably from the WHO model-based estimates.
Papillary microcarcinomas of the thyroid gland and immunohistochemical analysis of expression of p53 protein in papillary microcarcinomas
Authors: Corapcioglu Demet , Sak Serpil D , Delibasi Tuncay , Tonyukuk Vedia , Kamel Nuri , Uysal Ali R , Kocak Savas , Aydintug Semih , Erdogan Gurbuz
Published: August 2006

Background

Thyroid papillary microcarcinoma (TPM) is defined according to WHO criteria as a thyroid tumor smaller than 1–1.5 cm. TPMs are encountered in 0.5–35.6 % of autopsies or surgical specimens where carcinoma had been unsuspected. The purpose of the present study was to evaluate patients who had TPMs in terms of clinical findings, histopathological features and immunohistochemical evidence of expression of the tumor suppressor gene p53.

Methods

A total of 44 patients with TPMs less than 1.0 cm in diameter were included in the study. The patients were evaluated clinically and the tumors were evaluated in terms of their histopathological and immunohistochemical features, including expression of p53.

Results

The female/male ratio was 2.8/1, and the median age at time of diagnosis was 49 years (range 20–71 years). The maximum diameter of the smallest focus was 0.1 mm, and that of the largest was 10 mm microscopically. The mean diameter of all tumors was 5.7 mm. There was no correlation between tumor size and age or gender. Of the TPMs, 72 % were found in the right lobe, 24 % in the left lobe and 4 % in the isthmus. Fine-needle aspiration biopsy provided the diagnosis of TPM in only 43.2 % of the patients. All patients were treated with surgery, with 20 undergoing conservative surgery, i.e. lobectomy or isthmusectomy, and 24 undergoing total thyroidectomy. Frozen section provided the diagnosis of TPM in only 56.8 % of the patients. We found lymphocytic thyroiditis in 13.6% of patients, follicular variants in 11.9%, capsular invasion in 26.8%, lymph node involvement in 11.9%, soft tissue metastases in the neck in 12.1% and multifocality in 31.7 %, and none of these were related to age or gender (p > 0.05). No distant metastases were observed during approximately 10 years of follow up. We found p53 positivity in 34.5 % of TPM tumors. However, p53 expression was not statistically related to age or gender.

Conclusion

Our findings imply that TPMs may not be entirely innocent since they are associated with signs of poor prognosis such as capsular invasion, multifocal presentation, lymph node involvement and p53 positivity. Therefore, TPMs should be evaluated and followed like classical papillary cancers.
Astrogliosis is delayed in type 1 interleukin-1 receptor-null mice following a penetrating brain injury
Authors: Lin Hsiao-Wen , Basu Anirban , Druckman Charles , Cicchese Michael , Krady J Kyle , Levison Steven W
Published: August 2006

The cytokines IL-1α and IL-1β are induced rapidly after insults to the CNS, and their subsequent signaling through the type 1 IL-1 receptor (IL-1R1) has been regarded as essential for a normal astroglial and microglial/macrophage response. To determine whether abrogating signaling through the IL-1R1 will alter the cardinal astrocytic responses to injury, we analyzed molecules characteristic of activated astrocytes in response to a penetrating stab wound in wild type mice and mice with a targeted deletion of IL-1R1. Here we show that after a stab wound injury, glial fibrillary acidic protein (GFAP) induction on a per cell basis is delayed in the IL-1R1-null mice compared to wild type counterparts. However, the induction of chondroitin sulfate proteoglycans, tenascin, S-100B as well as glutamate transporter proteins, GLAST and GLT-1, and glutamine synthetase are independent of IL-1RI signaling. Cumulatively, our studies on gliosis in the IL-1R1-null mice indicate that abrogating IL-1R1 signaling delays some responses of astroglial activation; however, many of the important neuroprotective adaptations of astrocytes to brain trauma are preserved. These data recommend the continued development of therapeutics to abrogate IL-1R1 signaling to treat traumatic brain injuries. However, astroglial scar related proteins were induced irrespective of blocking IL-1R1 signaling and thus, other therapeutic strategies will be required to inhibit glial scarring.