bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence comparisons of plasmids pBJS-O of Spiroplasma citri and pSKU146 of S. kunkelii: implications for plasmid evolution
Authors: Joshi Bharat D , Berg Michael , Rogers Janet , Fletcher Jacqueline , Melcher Ulrich
Published: December 2005

Background

Spiroplasma citri BR3-3X and S. kunkelii CR2-3X cause serious diseases worldwide on citrus and maize species, respectively. S. citri BR3-3X harbors a plasmid, pBJS-Original (pBJS-O), that encodes the s piroplasma a dhesion r elated p rotein 1 (SARP1), a protein implicated in binding of the pathogen to cells of its leafhopper vector, Circulifer tenellus. The S. kunkelii CR2-3X plasmid, pSKU146, encodes a homolog of SARP1, Sk-ARP1. Due to the close phylogenetic relationship of the two pathogens, we hypothesized that the two plasmids are closely related as well.

Results

The nucleotide sequence of pBJS-O was determined and compared to the sequences of a plasmid from BR3-T (pBJS-T), which is a multiply passaged leafhopper transmissible derivative of BR3-3X, and to known plasmid sequences including that of pSKU146. In addition to arp1, the 13,374 bp pBJS-O sequence putatively contains nine genes, recognized as open reading frames (ORFs). Several pBJS-O ORFs have homologs on pSKU146. However, the sequences flanking soj-like genes on both plasmids were found to be more distant from one another than sequences in any other region. Further, unlike pSKU146, pBJS-O lacks the conserved oriT region characteristic of the IncP group of bacterial plasmids. We were unable to identify a region in pBJS-O resembling a known plasmid origin of transfer. In regions where sequence was available for the plasmid from both BR3-3X and BR3-T, the pBJS-T sequence had a 0.4 kb deletion relative to its progenitor, pBJS-O. Southern blot hybridization of extrachromosomal DNA from various S. citri strains and spiroplasma species to an arp-specific probe and a probe made from the entire plasmid DNA of BR3-3X revealed limited conservation of both sequences in the genus Spiroplasma. Finally, we also report the presence on the BR3-3X chromosome of arp2, an S. citri homolog of arp1 that encodes the predicted protein SARP2. The C-terminal domain of SARP2 is homologous to that of SARP1, but its N-terminal domain is distinct.

Conclusion

Our data suggest that pBJS is a novel S. citri plasmid that does not belong to any known plasmid incompatibility group. The differences between pBJS-O and pSKU146 suggest that one or more events of recombination have contributed to the divergence of the plasmids of the two sister Spiroplasma species; the plasmid from S. citri itself has diverged slightly during the derivation of S. citri BR3-T from BR3-3X. Our data also show that pBJS-O encodes the putative adhesin SARP1. The presence of traE and mob on pBJS-O suggests a role for the plasmid in spiroplasmal conjugation.
ASAP: Amplification, sequencing & annotation of plastomes
Authors: Dhingra Amit , Folta Kevin M
Published: December 2005

Background

Availability of DNA sequence information is vital for pursuing structural, functional and comparative genomics studies in plastids. Traditionally, the first step in mining the valuable information within a chloroplast genome requires sequencing a chloroplast plasmid library or BAC clones. These activities involve complicated preparatory procedures like chloroplast DNA isolation or identification of the appropriate BAC clones to be sequenced. Rolling circle amplification (RCA) is being used currently to amplify the chloroplast genome from purified chloroplast DNA and the resulting products are sheared and cloned prior to sequencing. Herein we present a universal high-throughput, rapid PCR-based technique to amplify, sequence and assemble plastid genome sequence from diverse species in a short time and at reasonable cost from total plant DNA, using the large inverted repeat region from strawberry and peach as proof of concept. The method exploits the highly conserved coding regions or intergenic regions of plastid genes. Using an informatics approach, chloroplast DNA sequence information from 5 available eudicot plastomes was aligned to identify the most conserved regions. Cognate primer pairs were then designed to generate ~1 – 1.2 kb overlapping amplicons from the inverted repeat region in 14 diverse genera.

Results

100% coverage of the inverted repeat region was obtained from Arabidopsis, tobacco, orange, strawberry, peach, lettuce, tomato and Amaranthus. Over 80% coverage was obtained from distant species, including Ginkgo, loblolly pine and Equisetum. Sequence from the inverted repeat region of strawberry and peach plastome was obtained, annotated and analyzed. Additionally, a polymorphic region identified from gel electrophoresis was sequenced from tomato and Amaranthus. Sequence analysis revealed large deletions in these species relative to tobacco plastome thus exhibiting the utility of this method for structural and comparative genomics studies.

Conclusion

This simple, inexpensive method now allows immediate access to plastid sequence, increasing experimental throughput and serving generally as a universal platform for plastid genome characterization. The method applies well to whole genome studies and speeds assessment of variability across species, making it a useful tool in plastid structural genomics.
The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait
Authors: Schena Francesco P , Cerullo Giuseppina , Torres Diletta D , Scolari Francesco , Foramitti Marina , Amoroso Antonio , Pirulli Doroti , Floege Jürgen , Mertens Peter R , Zerres Klaus , Alexopoulos Efstathios , Kirmizis Dimitrios , Zelante Leopoldo , Bisceglia Luigi , Ghiggeri Gian M , Frascà Giovanni M ,   the European IgA nephropathy Consortium
Published: December 2005

Background

IgA nephropathy (IgAN) or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22–23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes.

Description

The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: http://www.igan.net). The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents), 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5th Framework Programme 1998–2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: http://www.cordis.lu/marketplace.

Conclusion

The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained from the study of Mendelian diseases has shown that the genetic dissection of a complex trait is more powerful when combined linkage-based, association-based, and sequence-based approaches are performed. This Biobank continuously expanded contains a sample size of adequately matched IgAN patients and healthy subjects, extended multiplex pedigrees, parent-child trios, thus permitting the combined genetic approaches with collaborative studies.
Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies
Authors: Tichelaar Jay W , Zhang Yu , leRiche Jean C , Biddinger Paul W , Lam Stephen , Anderson Marshall W
Published: December 2005

Background

The development of non-small cell lung carcinoma proceeds through a series of well-defined pathological steps before the appearance of invasive lung carcinoma. The molecular changes that correspond with pathology changes are not well defined and identification of the molecular events may provide clues on the progression of intraepithelial neoplasia in the lung, as well as suggest potential targets for chemoprevention. The acquisition of anti-apoptotic signals is critical for the survival of cancer cells but the pathways involved are incompletely characterized in developing intra-epithelial neoplasia (IEN).

Methods

We used immunohistochemistry to determine the presence, relative levels, and localization of proteins that mediate anti-apoptotic pathways in developing human bronchial neoplasia.

Results

Bronchial epithelial protein levels of the phosphorylated (active) form of AKT kinase and the caspase inhibitor cIAP-2 were increased in more advanced grades of bronchial IEN lesions than in normal bronchial epithelium. Additionally, the percentage of biopsies with nuclear localization of p65/RELA in epithelial cells increased with advancing pathology grade, suggesting that NF-κB transcriptional activity was induced more frequently in advanced IEN lesions.

Conclusion

Our results indicate that anti-apoptotic pathways are elevated in bronchial IEN lesions prior to the onset of invasive carcinoma and that targeting these pathways therapeutically may offer promise in prevention of non-small cell lung carcinoma.
The impact of national and international guidelines on newborn care in the nurseries of Piedmont and Aosta Valley, Italy
Authors: Guala Andrea , Guarino Roberta , Zaffaroni Mauro , Martano Claudio , Fabris Claudio , Pastore Guido , Bona Gianni ,   the Neonatal Piedmont Group
Published: December 2005

Background

Care procedures for preventing neonatal diseases are carried out according to nurseries' traditions and may be not consistent with the evidence based medicine issues.

Methods

A multi-centric survey was conducted in 2 Regions located in NW Italy (Piedmont and Aosta Valley) in order to collect information on some healthy newborn care procedures. During 2001, a questionnaire was sent to the chief pediatrician in charge to the all 33 nurseries of the region asking the methods used during 2000 as prevention of ophthalmia neonatorum, early and late hemorrhagic disease of newborn, umbilical cord care and recommendations of vitamin D administration. Thereafter, during 2004 the same questionnaire was sent to the 34 chief pediatrician of nurseries to evaluate if the procedures were changed during 2003 according to guidelines. The nurseries care for 32,516 newborns in 2000 and 37,414 in 2003.

Results

Aminoglycoside eyes drops as prevention of ophthalmia neonatorum were the first choice in both periods (23 out 33 nurseries in 2000 and 24 out 34 in 2003 p > 0.05; the corresponding figures for newborns were18,984 out 32,516 newborns vs. 28,180 out of 37,414 p < 0.05). The umbilical cord care was carried out with alcohol in 12/33 centers (13,248 newborns) and dry gauze in 3/33 centers (2,130 newborns) in 2000, the corresponding figures in 2003 were 6/34 centers (p > 0.05), (6,380 newborns, p < 0.05) and 12/34 centers (p < 0.05), (18,123 newborns, p < 0.05). The percentage of newborns receiving of i.m. vitamin K. at birth increased during the study period (15,923/32,104 in 2000 vs. 19,684/37,414 in 2003, p < 0.01), but not the number of nurseries (16 in 2000 and 17 in 2003 p > 0.05). The numbers of parents of newborns who receive the recommendations of oral vitamin K during the first months life decreased from 2000 (25,516/30,606) to 2003 (29,808/37,414, p < 0.01) as well as for Vitamin D recommendation (14,582/30,616 in 2000 vs. 11,051/37,414 in 2003, p < 0.01). Oral vitamin K during the first months of life was recommended by 25 nurseries in 2000 and 27 in 2003 (p > 0.05), the corresponding figures for Vitamin D were 15 and 14 (p > 0.05).

Conclusion

In the present study a large variability of procedures among the nurseries was observed. During the study periods, guidelines and evidence based medicine issues have only partially modified the neonatal care procedures In Piedmont and Aosta Valley nurseries. These observations suggest to implement local forum/consensus conference to standardized procedures as much as possible.
Patterns of alcohol drinking and its association with obesity: data from the third national health and nutrition examination survey, 1988–1994
Authors: Arif Ahmed A , Rohrer James E
Published: December 2005

Background

Recent reports suggest that alcohol use may have a protective effect on obesity. This study explores association between obesity and alcohol consumption in the non-smoking U.S. adult population.

Methods

We analyzed data on a total of 8,236 respondents who participated in the Third National Health and Nutrition Examination Survey. Body mass index (weight-kg/height-m2) was derived from measured height and weight data and categorized into: normal weight, overweight, and obese. Alcohol consumption was measured using following measures: history of drinking, binge drinking, quantity of drinks/day, frequency of drinking, and average volume of drinks/week.

Results

Mean body mass index in this sample of non-smokers was 26.4 (95% CI: 26.1, 26.7). Approximately 46% of respondents were classified as current drinkers. Current drinkers had lower odds of obesity (Adjusted odds ratio = 0.73, 95% CI: 0.55, 0.97) as compared to non-drinkers. The odds of overweight and obesity were significantly greater among binge drinkers and those consuming four or more drinks/day. However, those who reported drinking one or two drinks per day had 0.46 (95% CI: 0.34, 0.62) and 0.59 (95% CI: 0.41, 0.86) times the odds of obesity, respectively. Similarly, the odds of obesity were significantly lower among those who reported drinking frequently and consuming less than five drinks per week. The association between overweight and other alcohol measures was less pronounced.

Conclusion

The results suggest further exploring the possible role of moderate alcohol drinking in controlling body weight in adults.
Erratum to: Mechanical properties of femoral trabecular bone in dogs
Authors: Pressel Thomas , Bouguecha Anas , Vogt Ute , Meyer-Lindenberg Andrea , Behrens Bernd-Arno , Nolte Ingo , Windhagen Henning
Published: December 2005

After the publication of this work [1], we became aware of the fact that the frequency of the ultrasound transmitter that we used for determining the elastic moduli of the trabecular bone specimens was not correctly specified. The oscillation frequency of the ultrasound transmitter was 2 MHz (and not 100 MHz as stated in our work) while we used a sampling rate of 100 MHz. In our publication, the oscillation frequency and sampling rate were confounded. Therefore also the statement in the discussion that we might have determined elastic moduli of trabecular bone tissue rather than the elastic properties of whole specimens because we used an ultrasound frequency > 2 MHz is wrong and has to be omitted.

For measurement, the cubic bone specimens were not immersed in Ringer's solution but only were kept moist all the time.

Apart from these corrections concerning the methods and interpretation of the data, the results reported in our publication and the conclusions are absolutely correct.

We apologize for the inconvenience that this inaccuracy may have caused.
Regenerative and fibrotic pathways in canine hepatic portosystemic shunt and portal vein hypoplasia, new models for clinical hepatocyte growth factor treatment
Authors: Spee Bart , Penning Louis C , van den Ingh Ted SGAM , Arends Brigitte , IJzer Jooske , van Sluijs Frederik J , Rothuizen Jan
Published: December 2005

Background

We analyzed two spontaneous dog diseases characterized by subnormal portal perfusion and reduced liver growth: (i) congenital portosystemic shunts (CPSS) without fibrosis and (ii) primary portal vein hypoplasia (PPVH), a disease associated with fibrosis. These pathologies, that lack inflammation or cholestasis, may represent simplified models to study liver growth and fibrosis. To investigate the possible use of those models for hepatocyte growth factor (HGF) treatment, we studied the functionality of HGF signaling in CPSS and PPVH dogs and compared this to aged-matched healthy controls.

Results

We used quantitative real-time polymerase chain reaction (Q-PCR) to analyze the mRNA expression of HGF, transforming growth factor β1 (TGF-β1), and relevant mediators in liver biopsies from cases with CPSS or PPVH, in comparison with healthy control dogs. CPSS and PPVH were associated with a decrease in mRNA expression of HGF and of MET proto-oncogene (c-MET). Western blot analysis confirmed the Q-PCR results and showed that intracellular signaling components (protein kinase B/Akt, ERK1/2, and STAT3) were functional. The TGF-β1 mRNA levels were unchanged in CPSS whereas there was a 2-fold increase in PPVH indicating an active TGF-β1 pathway, consistent with the observation of fibrosis seen in PPVH. Western blots on TGF-β1 and phosphorylated Smad2 confirmed an activated pro-fibrotic pathway in PPVH. Furthermore, Q-PCR showed an increase in the amount of collagen I present in PPVH compared to CPSS and control, which was confirmed by Western blot analysis.

Conclusion

The pathophysiological differences between CPSS and PPVH can adequately be explained by the Q-PCR measurements and Western blots. Although c-MET levels were reduced, downstream signaling seemed to be functional and provides a rational for HGF-supplementation in controlled studies with CPSS and PPVH. Furthermore both diseases may serve as simplified models for comparison with more complex chronic inflammatory diseases and cirrhosis.
Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis
Authors: Hollox Edward J , Davies Jane , Griesenbach Uta , Burgess Juliana , Alton Eric WFW , Armour John AL
Published: December 2005

Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.
The reliability, validity and responsiveness of the Restless Legs Syndrome Quality of Life questionnaire (RLSQoL) in a trial population
Authors: Abetz Linda , Arbuckle Robert , Allen Richard P , Mavraki Elena , Kirsch Jeffrey
Published: December 2005

Background

The aim of this study was to determine the reliability, validity and responsiveness of the Restless Legs Syndrome Quality of Life questionnaire (RLSQoL) in a clinical trial setting.

Methods

Two matching, placebo-controlled, multinational studies assessing the effectiveness and safety of ropinirole for treating moderate-to-severe Restless Legs Syndrome (RLS) formed the basis of this psychometric assessment. Validity and reliability were assessed using baseline data. Responsiveness was determined using longitudinal data collected at baseline and 12 weeks.

Results

A total of 547 subjects formed the baseline validation population; 519 were used for assessing responsiveness (n = 284/263 and 271/248 for both studies, respectively). Construct validity assessment confirmed that an overall life impact score could be calculated. All item-scale correlations were = 0.4, except items 1 (r = 0.36) and 5 (r = 0.35) in one study. Floor and ceiling effects were minimal. Cronbach's alpha values were 0.82 and 0.87, respectively, confirming internal consistency reliability. Correlations with the International Restless Legs Syndrome Study Group's severity rating scale (International Restless Legs Scale; IRLS) were moderate (r = -0.68 and -0.67, respectively; p < 0.0001). The RLSQoL was able to discriminate between levels of sleep problems (p < 0.0001) and between levels of global health status determined by a Clinical Global Impression of severity (CGI-S) (p < 0.0001). Responsiveness was demonstrated by significant differences in overall life impact change scores between CGI improvement levels after 12 weeks (p < 0.0001).

Conclusion

The RLSQoL is a valid, reliable and responsive measure of quality of life for patients with RLS, in a clinical trial setting where group comparisons are anticipated.
Quality of life after acute myocardial infarction: A comparison of diabetic versus non-diabetic acute myocardial infarction patients in Quebec acute care hospitals
Authors: Simpson Ewurabena , Pilote Louise
Published: December 2005

Background

Previous studies have evaluated the individual effects of acute myocardial infarction (AMI) and diabetes mellitus on health-related quality of life outcomes (QOL). Due to the rising incidence of these comorbid conditions, it is important to examine the synergistic impact of diabetes mellitus and AMI on QOL.

Methods

In this study, we assessed using several previously validated questionnaires the QOL and functional status of 96 diabetic patients and 491 non-diabetic patients admitted to Quebec hospital sites with AMI between 1997 and 1998. We also conducted multivariate analyses to ascertain whether diabetes mellitus was an independent determinant of SF-36 physical functioning (PCS) and mental health (MCS) component score QOL outcomes after AMI.

Results

Both patient groups had similar baseline clinical characteristics, but diabetic patients had slightly higher rates of cardiac risk factors compared to non-diabetics. Overall, QOL measures were similar between both patient groups at baseline, but diabetic patients reported poorer functional status than non-diabetic patients. Over the study period, there were significant differences between the QOL and functional status of diabetic and non-diabetic populations. By one year, diabetic patients reported poorer QOL outcomes than non-diabetic patients. However, diabetic patients showed greater improvements in their functional status, but were less likely to return to work compared to non-diabetic patients. In contrast with these findings, our multivariate analyses showed that diabetes mellitus was not an independent determinant of QOL and functional status.

Conclusion

Our study findings suggest that diabetes mellitus is not an independent determinant of QOL after AMI.
Cloning and expression of two new prolactin-related proteins, prolactin-related protein-VIII and -IX, in bovine placenta
Authors: Ushizawa Koichi , Takahashi Toru , Hosoe Misa , Kaneyama Kanako , Hashizume Kazuyoshi
Published: December 2005

Background

Prolactin-related proteins (PRPs) are specific proteins of the growth hormone/prolactin (GH/PRL) family in bovine placenta. This study reports the identification and sequencing of a full-length cDNA for two new members of bovine PRPs, bPRP-VIII and -IX, and their localization and quantitative expression in bovine placenta.

Methods

New bPRP-VIII and -IX were identified from bovine placentome. Localization and quantitative gene expression in the placenta were respectively investigated by in situ hybridization and real-time RT-PCR methods. Recombinant proteins of these genes were produced by a mammalian HEK293 cell expression system.

Results

Full-length bPRP-VIII and -IX cDNA were respectively cloned with 909 and 910 nucleotide open-reading-frames corresponding to proteins of 236 and 238 amino acids. The predicted bPRP-VIII amino acid sequence shared about 40 to 70% homology with other bPRPs, and bPRP-IX had about 50 to 80 % homology of others. The two new bPRPs were detected only in the placenta by RT-PCR. mRNA was primarily expressed in the cotyledon and intercotyledonary tissues throughout gestation. An in situ hybridization analysis revealed the presence of bPRP-VIII and -IX mRNA in the trophoblastic binucleate and/or trinucleate cells. bPRP-VIII mRNA was observed in the extra-embryonic membrane on Day 27 of gestation, however, no bPRP-IX mRNA was observed in the extra-embryonic membrane in the same stage of pregnancy by quantitative real-time RT-PCR analysis. Both new bPRP genes were possible to translate a mature protein in a mammalian cell expression system with approximately 28 kDa in bPRP-VIII and 38 kDa in bPRP-IX.

Conclusion

We identified the new members of bovine prolactin-related protein, bPRP-VIII and -IX. Localization and quantitative expression were confirmed in bovine placenta by in situ hybridization or real-time PCR. Their different temporal and spatial expressions suggest a different role for these genes in bovine placenta during gestation.
Novel Aβ peptide immunogens modulate plaque pathology and inflammation in a murine model of Alzheimer's disease
Authors: Zhou Jun , Fonseca Maria I , Kayed Rakez , Hernandez Irma , Webster Scott D , Yazan Ozkan , Cribbs David H , Glabe Charles G , Tenner Andrea J
Published: December 2005

Background

Alzheimer's disease, a common dementia of the elder, is characterized by accumulation of protein amyloid deposits in the brain. Immunization to prevent this accumulation has been proposed as a therapeutic possibility, although adverse inflammatory reactions in human trials indicate the need for novel vaccination strategies.

Method

Here vaccination with novel amyloid peptide immunogens was assessed in a transgenic mouse model displaying age-related accumulation of fibrillar plaques.

Results

Immunization with any conformation of the amyloid peptide initiated at 12 months of age (at which time fibrillar amyloid has just begun to accumulate) showed significant decrease in total and fibrillar amyloid deposits and in glial reactivity relative to control transgenic animals. In contrast, there was no significant decrease in amyloid deposition or glial activation in mice in which vaccination was initiated at 16 months of age, despite the presence of similar levels anti-Aβ antibodies in young and old animals vaccinated with a given immunogen. Interestingly, immunization with an oligomeric conformation of Aβ was equally as effective as other amyloid peptides at reducing plaque accumulation. However, the antibodies generated by immunization with the oligomeric conformation of Aβ have more limited epitope reactivity than those generated by fAβ, and the microglial response was significantly less robust.

Conclusion

These results suggest that a more specific immunogen such as oligomeric Aβ can be designed that achieves the goal of depleting amyloid while reducing potential detrimental inflammatory reactions. In addition, the data show that active immunization of older Tg2576 mice with any amyloid conformation is not as efficient at reducing amyloid accumulation and related pathology as immunization of younger mice, and that serum anti-amyloid antibody levels are not quantitatively related to reduced amyloid-associated pathology.
The "impact factor" revisited
Authors: Dong Peng , Loh Marie , Mondry Adrian
Published: December 2005

The number of scientific journals has become so large that individuals, institutions and institutional libraries cannot completely store their physical content. In order to prioritize the choice of quality information sources, librarians and scientists are in need of reliable decision aids. The "impact factor" (IF) is the most commonly used assessment aid for deciding which journals should receive a scholarly submission or attention from research readership. It is also an often misunderstood tool. This narrative review explains how the IF is calculated, how bias is introduced into the calculation, which questions the IF can or cannot answer, and how different professional groups can benefit from IF use.
Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages
Authors: Barlow Peter G , Clouter-Baker Anna , Donaldson Ken , MacCallum Janis , Stone Vicki
Published: December 2005

Background

Alveolar macrophages are a key cell in dealing with particles deposited in the lungs and in determining the subsequent response to that particle exposure. Nanoparticles are considered a potential threat to the lungs and the mechanism of pulmonary response to nanoparticles is currently under intense scrutiny. The type II alveolar epithelial cell has previously been shown to release chemoattractants which can recruit alveolar macrophages to sites of particle deposition. The aim of this study was to assess the responses of a type II epithelial cell line (L-2) to both fine and nanoparticle exposure in terms of secretion of chemotactic substances capable of inducing macrophage migration.

Results

Exposure of type II cells to carbon black nanoparticles resulted in significant release of macrophage chemoattractant compared to the negative control and to other dusts tested (fine carbon black and TiO2and nanoparticle TiO2) as measured by macrophage migration towards type II cell conditioned medium. SDS-PAGE analysis of the conditioned medium from particle treated type II cells revealed that a higher number of protein bands were present in the conditioned medium obtained from type II cells treated with nanoparticle carbon black compared to other dusts tested. Size-fractionation of the chemotaxin-rich supernatant determined that the chemoattractants released from the epithelial cells were between 5 and 30 kDa in size.

Conclusion

The highly toxic nature and reactive surface chemistry of the carbon black nanoparticles has very likely induced the type II cell line to release pro-inflammatory mediators that can potentially induce migration of macrophages. This could aid in the rapid recruitment of inflammatory cells to sites of particle deposition and the subsequent removal of the particles by phagocytic cells such as macrophages and neutrophils. Future studies in this area could focus on the exact identity of the substance(s) released by the type II cells in response to particle exposure.
Partial protection against collagen antibody-induced arthritis in PARP-1 deficient mice
Authors: García Samuel , Bodaño Ana , González Antonio , Forteza Jerónimo , Gómez-Reino Juan J , Conde Carmen
Published: December 2005

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear DNA-binding protein that participates in the regulation of DNA repair and maintenance of genomic integrity. In addition, PARP-1 has a role in several models of inflammation disease, where its absence or inactivation confers protection. The aim of this study was to analyze the impact of selective PARP-1 suppression in collagen antibody-induced arthritis. We show that PARP-1 deficiency partially reduces the severity of arthritis, although the incidence of disease was similar in control and deficient mice. Decreased clinical scores were accompanied by partial reduction of histopathological findings. Interestingly, quantitative real-time PCR and ELISA analysis revealed that the absence of PARP-1 down-regulated IL-1β and monocyte chemotactic protein 1 expression in arthritic joints whereas tumor necrosis factor-α transcription was not impaired. Our results provide evidence of the contribution of PARP-1 to the progression of arthritis and identify this protein as a potential therapeutic target for the treatment of rheumatoid arthritis.
A preliminary study on the monitoring of mixed venous oxygen saturation through the left main bronchus
Authors: Wang Xiang-rui , Zheng Yong-jun , Tian Jie , Wang Zheng-hong , Pan Zhi-ying
Published: December 2005

Introduction

The study sought to assess the feasibility and accuracy of measuring mixed venous oxygen saturation (SvO2) through the left main bronchus (SpO2trachea)

Methods

Twenty hybrid pigs of each sex were studied. After anesthesia, a Robertshaw double-lumen tracheal tube with a single-use pediatric pulse oximeter attached to the left lateral surface was introduced toward the left main bronchus of the pig by means of a fibrobronchoscope. Measurements of SpO2trachea and oxygen saturation from pulmonary artery samples (SvO2blood) were performed with an intracuff pressure of 0 to 60 cmH2O. After equilibration, hemorrhagic shock was induced in these pigs by bleeding to a mean arterial blood pressure of 40 mmHg. With the intracuff pressure maintained at 60 cmH2O, SpO2trachea and SvO2blood were obtained respectively during the pre-shock period, immediately after the onset of shock, 15 and 30 minutes after shock, and 15, 30, and 60 minutes after resuscitation.

Results

SpO2trachea was the same as SvO2blood at an intracuff pressure of 10, 20, 40, and 60 cmH2O, but was reduced when the intracuff pressure was zero (p < 0.001 compared with SvO2blood) in hemodynamically stable states. Changes of SpO2trachea and SvO2blood corresponded with varieties of cardiac output during the hemorrhagic shock period. There was a significant correlation between the two methods at different time points.

Conclusion

Measurement of the left main bronchus SpO2 is feasible and provides similar readings to SvO2blood in hemodynamically stable or in low saturation states. Tracheal oximetry readings are not primarily derived from the tracheal mucosa. The technique merits further evaluation.
The impact of empiric antimicrobial therapy with a β-lactam and fluoroquinolone on mortality for patients hospitalized with severe pneumonia
Authors: Mortensen Eric M , Restrepo Marcos I , Anzueto Antonio , Pugh Jacqueline
Published: December 2005

Introduction

National clinical practice guidelines have recommended specific empiric antimicrobial regimes for patients with severe community-acquired pneumonia. However, evidence confirming improved mortality with many of these regimes is lacking. Our aim was to determine the association between the empiric use of a β-lactam with fluoroquinolone, compared with other recommended antimicrobial therapies, and mortality in patients hospitalized with severe community-acquired pneumonia.

Methods

A retrospective observational study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of community-acquired pneumonia and had a chest X-ray and a discharge ICD-9 diagnosis consistent with this. Subjects were excluded if they received 'comfort measures only' during the admission, had been transferred from another acute care hospital, did not meet criteria for severe pneumonia, or were treated with non-guideline-concordant antibiotics. A multivariable logistic regression model was used to assess the association between 30-day mortality and the use of a β-lactam antibiotic with a fluoroquinolone compared with other guideline-concordant therapies, after adjustment for potential confounders including a propensity score.

Results

Data were abstracted on 172 subjects at the two hospitals. The mean age was 63.5 years (SD 15.0). The population was 88% male; 91% were admitted through the emergency department and 62% were admitted to the intensive care unit within the first 24 hours after admission. Mortality was 19.8% at 30 days. After adjustment for potential confounders the use of a β-lactam with a fluoroquinolone (odds ratio 2.71, 95% confidence interval 1.2 to 6.1) was associated with increased mortality.

Conclusion

The use of initial empiric antimicrobial therapy with a β-lactam and a fluoroquinolone was associated with increased short-term mortality for patients with severe pneumonia in comparison with other guideline-concordant antimicrobial regimes. Further research is needed to determine the range of appropriate empiric antimicrobial therapies for patients with severe community-acquired pneumonia.
Concentrations of nano and related ambient air pollutants at a traffic sampling site
Authors: Fang Guor-Cheng , Wu Yuh-Shen , Wen Chih-Chung , Lin Chi-Kwong , Huang Shih-Han , Rau Jui-Yeh , Lin Chung-Po
Published: December 2005

A micro-orifice uniform deposit impactor (MOUDI) and a nano-MOUDI were used to measure the atmospheric coarse (PM2.5- 10), fine (PM2.5), ultrafine (PM0.056 - 1) and nano (< 0.056 μm) particle concentrations and size distributions at a traffic sampling site in winter in central Taiwan, from November 2004 to January 2005. Concentrations of metallic elements (Fe, Mg, Cr, Zn, Pb, Cu) and major ion (SO2-4; NO-3; NH+4) in particles of various sizes (nano, ultrafine, fine and coarse) were measured. Ambient air particulates generally exhibited a bimodal size distribution in the range 0.056-10 mm. The results show that the concentrations followed the order, Fe-Mg-Cr-Zn-Pb-Cu in PM10, fine, ultrafine and nano-sized particles. Moreover, the data showed that the average metallic elements Fe and Zn have similar concentration distributions: the concentration decreased as the particle size fell in the nano size range.
Effect of formaldehyde inhalation on Hsp70 in seminiferous tubules of rat testes: an immunohistochemical study
Authors: Özen Oğuz Aslan , Akpolat Nusret , Songur Ahmet , Kuş İlter , Zararsiz İsmail , Özaçmak Veysel Haktan , Sarsilmaz Mustafa
Published: December 2005

One parameter which might provide an insight into the underlying mechanism of the effect of formaldehyde (FA) inhalation on testicular tissue, is the assessment of heat shock protein 70 (Hsp70), which increases promptly in cells exposed to stress caused by chemical toxicity. Thus, following subchronic exposure at cytotoxic concentrations, we studied the immunohistochemical effect of FA inhalation on changes in Hsp70 content in testicular tissue.

We used 18 albino Wistar rats divided into three groups, exposed to 0 (control), 5 and 10 ppm FA gas for a total of 91 days, 8 h/day, five days a week. Serum testosterone levels were determined using a chemiluminescent enzyme immunoassay. Testicular tissues were stained with Hematoxylin-Eosine and Hsp70 immunohistochemically performed. Diameters of seminiferous tubules and serum testosterone levels in animals inhaling FA were significantly decreased. In seminiferous epithelium stained for Hsp70, compared to those in the control group, the spermatogenetic cells in the experimental groups demonstrated an obvious increase in immunoreaction spermatides in the adluminal region and especially in the cytoplasm of spermatocytes. Immunoreaction of Hsp70 was detected in the spermatogonias of animals exposed to FA inhalation as opposed to those of the control group. Compared to the control, there was a significant increase in the immunoreactions observed not only in the cytoplasm of primary spermatocytes, but also spermatides in the adluminal region of the seminiferous tubules.

In conclusion, FA gas may damage spermatogenetic cells and increase Hsp70 synthesis.
Cancer incidence among male military and civil pilots and flight attendants: an analysis on published data
Authors: Buja Alessandra , Lange John H , Perissinotto Egle , Rausa Giuseppe , Grigoletto Francesco , Canova Cristina , Mastrangelo Giuseppe
Published: December 2005

Flight personnel are exposed to cosmic ionizing radiation, chemicals (fuel, jet engine exhausts, cabin air pollutants), electromagnetic fields from cockpit instruments, and disrupted sleep patterns. Only recently has cancer risk among these workers been investigated. With the aim of increasing the precision of risk estimates of cancer incidence, follow-up studies reporting a standardized incidence ratio for cancer among male flight attendants, civil and military pilots were obtained from online databases and analysed. A meta-analysis was performed by applying a random effect model, obtaining a meta-standardized incidence ratio (SIR), and 95% confidence interval (CI). In male cabin attendants, and civil and military pilots, meta-SIRs were 3.42 (CI=1.94-6.06), 2.18 (1.69-2.80), 1.43 (1.09-1.87) for melanoma; and 7.46 (3.52-15.89), 1.88 (1.23-2.88), 1.80 (1.25-2.58) for other skin cancer, respectively. These tumors share as risk factors, ionizing radiation, recreational sun exposure and socioeconomic status. The meta-SIRs are not adjusted for confounding; the magnitude of risk for melanoma decreased when we corrected for socioeconomic status. In civil pilots, meta-SIR was 1.47 (1.06-2.05) for prostate cancer. Age (civil pilots are older than military pilots and cabin attendants) and disrupted sleep pattern (entailing hyposecretion of melatonin, which has been reported to suppress proliferative effects of androgen on prostate cancer cells) might be involved. In male cabin attendants, meta-SIR was 21.5 (2.25-205.8) for Kaposi’s sarcoma and 2.49 (1.03-6.03) for non-Hodgkin’s lymphoma. AIDS, which was the most frequent single cause of death in this occupational category, likely explains the excess of the latter two tumors.
Interaction of Nuclear Receptors with the Wnt/β-Catenin/Tcf Signaling Axis: Wnt You Like to Know?
Authors: Mulholland David J. , Dedhar Shoukat , Coetzee Gerhard A. , Nelson Colleen C.
Published: December 2005

The cross-regulation of Wnt/β-catenin/Tcf ligands, kinases, and transcription factors with members of the nuclear receptor (NR) family has emerged as a clinically and developmentally important area of endocrine cell biology. Interactions between these signaling pathways result in a diverse array of cellular effects including altered cellular adhesion, tissue morphogenesis, and oncogenesis. Analyses of NR interactions with canonical Wnt signaling reveal two broad themes: Wnt/β-catenin modulation of NRs (theme I), and ligand-dependent NR inhibition of the Wnt/β-catenin/Tcf cascade (theme II). β-Catenin, a promiscuous Wnt signaling member, has been studied intensively in relation to the androgen receptor (AR). β-Catenin acts as a coactivator of AR transcription and is also involved in cotrafficking, increasing cell proliferation, and prostate pathogenesis. T cell factor, a transcriptional mediator of β-catenin and AR, engages in a dynamic reciprocity of nuclear β-catenin, p300/CREB binding protein, and transcriptional initiation factor 2/GC receptor-interaction protein, thereby facilitating hormone-dependent coactivation and transrepression. β-Catenin responds in an equally dynamic manner with other NRs, including the retinoic acid (RA) receptor (RAR), vitamin D receptor (VDR), glucocorticoid receptor (GR), progesterone receptor, thyroid receptor (TR), estrogen receptor (ER), and peroxisome proliferator-activated receptor (PPAR). The NR ligands, vitamin D3, trans/cis RA, glucocorticoids, and thiazolidines, induce dramatic changes in the physiology of cells harboring high Wnt/β-catenin/Tcf activity. Wnt signaling regulates, directly or indirectly, developmental processes such as ductal branching and adipogenesis, two processes dependent on NR function. β-Catenin has been intensively studied in colorectal cancer; however, it is now evident that β-catenin may be important in cancers of the breast, prostate, and thyroid. This review will focus on the cross-regulation of AR and Wnt/β-catenin/Tcf but will also consider the dynamic manner in which RAR/RXR, GR, TR, VDR, ER, and PPAR modulate canonical Wnt signaling. Although many commonalities exist by which NRs interact with the Wnt/β-catenin signaling pathway, striking cell line and tissue-specific differences require deciphering and application to endocrine pathology.
The Insulin-Like Growth Factor System and Its Pleiotropic Functions in Brain
Authors: Russo V. C. , Gluckman P. D. , Feldman E. L. , Werther G. A.
Published: December 2005

In recent years, much interest has been devoted to defining the role of the IGF system in the nervous system. The ubiquitous IGFs, their cell membrane receptors, and their carrier binding proteins, the IGFBPs, are expressed early in the development of the nervous system and are therefore considered to play a key role in these processes. In vitro studies have demonstrated that the IGF system promotes differentiation and proliferation and sustains survival, preventing apoptosis of neuronal and brain derived cells. Furthermore, studies of transgenic mice overexpressing components of the IGF system or mice with disruptions of the same genes have clearly shown that the IGF system plays a key role in vivo.
Epoetin Alfa Versus Darbepoetin Alfa in Chemotherapy-Related Anemia
Authors: Cersosimo Robert J , Jacobson Daniel R
Published: December 2005

Objective:

To review and compare the data concerning the clinical activity of epoetin alfa versus darbepoetin alfa when administered to patients with cancer who are experiencing treatment-related anemia.

Data Sources:

English-language publications from the MEDLINE database (1990–June 2005), published articles, and meeting abstracts were reviewed.

Study Selection and Data Extraction:

Relevant data were extracted from published reports and abstracts on studies of humans with cancer who developed treatment-related anemia and were treated with epoetin alfa or darbepoetin alfa.

Data Synthesis:

Epoetin alfa and darbepoetin alfa are similar agents with identical indications for treatment of anemia in patients with cancer. Clinical trials have demonstrated that both agents can significantly improve hemoglobin levels, reduce transfusion requirements, and improve quality of life. Epoetin alfa is approved for administration at a dose of 150 units/kg subcutaneously 3 times per week, and darbepoetin alfa is approved for administration at a dose of 2.25 units/kg once a week. Clinical studies have demonstrated that epoetin alfa may be administered at 40 000 units once a week and that darbepoetin alfa may be administered at 200 μg every 2 weeks without loss of efficacy. Cost analysis, based on the average wholesale price of each drug alone administered for 12 weeks at Food and Drug Administration–approved doses, revealed that epoetin alfa is less expensive than darbepoetin alfa. When they are administered in the extended schedules, the cost of darbepoetin alfa is slightly less than that of epoetin alfa. However, the total expense associated with the extended schedule of either agent is further reduced by a reduction in other costs associated with drug administration.

Conclusions:

Epoetin alfa and darbepoetin alfa have identical indications for treatment of anemia in patients receiving cancer chemotherapy. Clinical trials have demonstrated similar activities with both agents. Darbepoetin alfa, with a longer half-life, can be administered less frequently, saving costs as well as reducing patient office visits.