bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of HCLCA1 in cystic fibrosis lungs is associated with mucus overproduction
Authors: Hauber H.P. , Tsicopoulos A. , Wallaert B. , Griffin S. , McElvaney N.G. , Daigneault P. , Mueller Z. , Olivenstein R. , Holroyd K.J. , Levitt R.C. , Hamid Q. 
Published: September 2008

Mucus overproduction is typical in cystic fibrosis (CF) airway disease. The human calcium-activated chloride channel, hCLCA1, has been reported to be upregulated by interleukin (IL)‐9 and to regulate the expression of mucins. Therefore, the expression of IL‐9, IL‐9 receptor (IL‐9R) and hCLCA1 between the lungs of CF patients and healthy control subjects was compared.Endoscopic biopsy samples of bronchial mucosa from 10 CF patients and six control subjects were stained with periodic acid-Schiff. IL‐9, IL‐9R and hCLCA1 expression was determined by immunocytochemistry. Expression of hCLCA1 mRNA was also determined byin situhybridisation.The present study found significant increases in IL‐9, IL‐9R and hCLCA1 immunoreactivity, hCLCA1 mRNA expression, and numbers of mucus-producing cells in the mucosa of CF patients compared to control subjects. Positive correlations were found between IL‐9R‐positive-cells with IL‐9‐positive cells and hCLCA1-positive cells, and between PAS-positive cells with hCLCA1-positive cells and IL‐9R‐positive cells. Expression of hCLCA1 mRNA was colocalised with IL‐9R expression and PAS-positive staining in epithelial cells.Increased expression of interleukin‐9 and interleukin‐9 receptor, as well as an upregulation of the human calcium-activated chloride channel, hCLCA1, in mucus-producing epithelium of cystic fibrosis patients, support the hypothesis that interleukin‐9 contributes to mucus overproduction in cystic fibrosis airway disease.
A case of steroid responsive pulmonary hyalinising granuloma: complicated by deep venous thrombosis
Authors: O'Reilly K.M.A. , Boscia J.A. , Kaplan K.L. , Sime P.J. 
Published: September 2008

A case of pulmonary hyalinising granuloma (PHG) complicated by deep venous thrombosis (DVT) is presented.The DVT was associated with the presence of a lupus anticoagulant. In the past PHG has been linked to various auto-antibodies, but to the best of the authors' knowledge, this is the first case reporting PHG in association with a lupus anticoagulant and clinically significant venous thrombosis. Historically, PHG has been regarded as poorly corticosteroid responsive. However, the patient in this case study responded dramatically to prednisone.This case study suggests that in selected patients with pulmonary hyalinising granuloma experiencing disabling symptoms and worsening pulmonary function, a trial of corticosteroids may be warranted.
Effect of smoking on MAP kinase-induced modulation of IL‐8 in human alveolar macrophages
Authors: Koch A. , Giembycz M. , Stirling R.G. , Lim S. , Adcock I. , Waßermann K. , Erdmann E. , Chung K.F. 
Published: September 2008

Inflammatory cytokine production by alveolar macrophages (AMs) is regulated by transcriptional activation and may be increased by cigarette smoking.The smoking-induced regulation of interleukin (IL)‐8 by extracellular signal-regulated kinase (ERK)‐1 and ‐2, p38 mitogen-activated protein kinase (MAPK) and the transcription factor nuclear factor‐κB (NF‐κB) in lipopolysaccharide-stimulated AMs was assessed in nine smokers compared with nine healthy nonsmokers.IL‐8 production was dependent on phosphorylation of ERK‐1 and ‐2 and p38 MAPK, as examined by PD 098059 (10 µM), an inhibitor of the upstream activator of MAPK kinase (MKK)‐1, and SB 203580 (10 µM), an inhibitor of p38 MAPK. IL‐8 release and the inhibitory effect of PD 098059 were increased in AMs from smokers. Moreover, ERK‐2 messenger ribonucleic acid expression, as examined by reverse transcriptase polymerase chain reaction and phosphorylation of ERK‐2 using Western blots, were increased in AMs from smokers, indicating a smoking-induced modulatory role of ERK‐1 and ‐2. Lipopolysaccharide-induced IL‐8 production was dependent on activation of NF‐κB, as examined by SN 50 (100 µM), an inhibitor of NF‐κB translocation, and the specific NF‐κB inhibitor kinase‐2 inhibitor, AS 602868 (10 µM), with no differences in AMs from smokers and nonsmokers. SN 50 but not PD 098059 and SB 203580 blocked NF‐κB deoxyribonucleic acid-binding, and this occurred to the same extent in AMs from smokers and nonsmokers, as examined by electromobility shift assay.It is concluded that cigarette smoking enhances mitogen-activated protein kinase activation more than nuclear factor‐κB activation to increase lipopolysaccharide-induced interleukin‐8 production in alveolar macrophages.
Genetic polymorphism of epoxide hydrolase and glutathione S-transferase in COPD
Authors: Cheng S‐L. , Yu C‐J. , Chen C‐J. , Yang P‐C. 
Published: September 2008

Genetic susceptibility to the development of chronic obstructive pulmonary disease (COPD) might depend on variation in the activities of enzymes that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEPHX) and glutathioneS-transferase (GST). It was investigated whether polymorphisms in these genes had any association with susceptibility to COPD and COPD severity.The genotypes of 184 patients with COPD and 212 control subjects were determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis of the mEPHX, GSTM1, GSTT1 and GSTP1 genes. All subjects were smokers or exsmokers.The proportion of GSTM1-null genotypes was significantly higher in patients with COPD than in control subjects (61.4versus42.5%). No differences were observed in the frequency of polymorphic genotypes for mEPHX, GSTT1 and GSTP1. During combined analysis of genetic polymorphisms for mEPHX, GSTM1 and GSTP1, it was found that there are strong indicators for susceptibility to COPD (genotype combination with at least one mutant mEPHX exon‐3 allele (histidine 113), GSTM1 null and homozygous for the GSTP1 isoleucine 105 allele). The frequencies of homozygous mutant alleles of mEPHX exon 3 and the GSTM1-null genotype were significantly higher in patients with severe COPD (forced expiratory volume in one second of <35% of the predicted value).It is proposed that the combination of genetic variants including at least one mutant microsomal epoxide hydrolase exon‐3 allele and glutathioneS-transferase M1-null and homozygous isoleucine 105 glutathioneS-transferase P1 genotypes are significant indicators of susceptibility to chronic obstructive pulmonary disease in the Taiwanese population. In addition, the homozygous variant of microsomal epoxide hydrolase exon 3 and the glutathioneS-transferase M1-null genotype are independent risk factors for developing severe chronic obstructive pulmonary disease.
Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial
Authors: Silvestri L. , van Saene H.K.F. , Milanese M. , Fontana F. , Gregori D. , Oblach L. , Piacente N. , Blazic M. 
Published: September 2008

This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin‐resistantStaphylococcus aureus(MRSA) acquired in the intensive care unit (ICU). Secondary endpoints were the emergence of vancomycin-resistant enterococci, vancomycin-intermediateS. aureusand vancomycin consumption.A total of 84 patients, admitted to a medical/surgical ICU and mechanically ventilated for >72 h, were randomly assigned to control (n=42) or test (n=42) group. Both groups received the protocol of selective decontamination of the digestive tract, including polymyxin E, tobramycin and amphotericin B. Patients in the test group received 0.5 g of a 4% vancomycin gel at 6‐h intervals in the oropharynx.Lower airway infections due to MRSA acquired on the ICU were reduced in the test group, as was oropharyngeal carriage. Neither vancomycin-resistant enterococci nor vancomycin-intermediateS. aureuswere isolated from either surveillance or diagnostic samples during the study period. The vancomycin costs were lower in the test group.This study demonstrates that oropharyngeal vancomycin, which controls intensive care unit‐acquired lower airway infections and secondary carriage due to methicillin-resistantStaphylococcus aureus, is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediateStaphylococcus aureus.
Epidemiology ofBurkholderia cepaciacomplex colonisation in cystic fibrosis patients
Authors: De Boeck K. , Malfroot A. , Van Schil L. , Lebecque P. , Knoop C. , Govan J.R.W. , Doherty C. , Laevens S. , Vandamme P. 
Published: September 2008

In Belgian cystic fibrosis (CF) clinics, sputum samples are evaluated on selective MAST medium routinely every 3 months. In this study, in 1993 and 1999, isolates were further examined byrecArestriction fragment length polymorphism analysis and pulsed-field gel electrophoresis of genomic DNA restricted withSpeI.In 1993, 12 patients were colonised withBurkholderia cepaciacomplex (Bcc):B. cenocepacia(n=6),B. multivorans(n=3),B. stabilis(n=3). Four patients were colonised with the sameB. cenocepaciastrain; two with the sameB. stabilisstrain. After 5 yrs, threeB. cenocepacia- and oneB. multivorans-colonised patients had died.In 1999, Bcc was isolated in 12 patients:B. multivorans(n=9),B. stabilis(n=1) andB. cenocepacia(n=2). Three patients were colonised by the sameB. multivoransstrain. Compared to matched controls, the 5 yr outcome was poor; fourB. cepaciapatients died and none of the control patients died. Lung-function evolution was poor.In conclusion, the rate of colonisation in Belgian cystic fibrosis patients is stable and low.Burkholderia cenocepaciawas most prevalent in 1993;Burkholderia multivoransin 1999. The cross-infection rate is low. Three patients had transient colonisation. The impact ofBurkholderia cepaciacomplex on morbidity in the Belgian cystic fibrosis population is high and not limited toBurkholderia cenocepacia.
End points in pulmonary arterial hypertension: the way forward
Authors: Peacock A. , Naeije R. , Galié N. , Reeves J.T. 
Published: September 2008

Pulmonary arterial hypertension is a rare disease of poor prognosis.Despite its rarity >1,000 patients have been randomised in placebo-controlled trials using novel therapies, including prostacyclin analogues, endothelin receptor antagonists and, most recently, phosphodiesterase 5 inhibitors. Nearly all of these trials have used exercise capacity, measured by the unencouraged 6‐min walking distance, as the primary end point and a variety of other measurements as secondary end points. This approach has been productive, leading to the licensing of a number of effective treatments. Future clinical trials, however, will probably assess drug combinations, make comparisons between drugs and include less severely ill patients. It is, therefore, timely to examine the end points used.The authors discussed the various end points that have been used in the past and possible end points that might be used in the future. End points considered included measurements of: exercise capacity, haemodynamics, quality of life, imaging of the right heart and circulation, and chemical markers of pulmonary hypertension.Many of these show promise but will have to be used in parallel and compared with conventional end points such as the 6‐min walking distance before their value can be demonstrated convincingly to the regulatory authorities.
Phylogenetic and chromosomal analyses of multiple gene families syntenic with vertebrate Hox clusters
Authors: Sundström Görel , Larsson Tomas A , Larhammar Dan 
Published: September 2008

Abstract

Background
Ever since the theory about two rounds of genome duplication (2R) in the vertebrate lineage was proposed, the Hox gene clusters have served as the prime example of quadruplicate paralogy in mammalian genomes. In teleost fishes, the observation of additional Hox clusters absent in other vertebrate lineages suggested a third tetraploidization (3R). Because the Hox clusters occupy a quite limited part of each chromosome, and are special in having position-dependent regulation within the multi-gene cluster, studies of syntenic gene families are needed to determine the extent of the duplicated chromosome segments. We have analyzed in detail 14 gene families that are syntenic with the Hox clusters to see if their phylogenies are compatible with the Hox duplications and the 2R/3R scenario. Our starting point was the gene family for the NPY family of peptides located near the Hox clusters in the pufferfish Takifugu rubripes, the zebrafish Danio rerio, and human.

Results
Seven of the gene families have members on at least three of the human Hox chromosomes and two families are present on all four. Using both neighbor-joining and quartet-puzzling maximum likelihood methods we found that 13 families have a phylogeny that supports duplications coinciding with the Hox cluster duplications. One additional family also has a topology consistent with 2R but due to lack of urochordate or cephalocordate sequences the time window when these duplications could have occurred is wider. All but two gene families also show teleost-specific duplicates.

Conclusion
Based on this analysis we conclude that the Hox cluster duplications involved a large number of adjacent gene families, supporting expansion of these families in the 2R, as well as in the teleost 3R tetraploidization. The gene duplicates presumably provided raw material in early vertebrate evolution for neofunctionalization and subfunctionalization.
Gene expression changes linked to antimicrobial resistance, oxidative stress, iron depletion and retained motility are observed when Burkholderia cenocepaciagrows in cystic fibrosis sputum
Authors: Drevinek Pavel , Holden Matthew TG , Ge Zhaoping , Jones Andrew M , Ketchell Ian , Gill Ryan T , Mahenthiralingam Eshwar 
Published: September 2008

Abstract

Background
Bacteria from the Burkholderia cepacia complex (Bcc) are the only group of cystic fibrosis (CF) respiratory pathogens that may cause death by an invasive infection known as cepacia syndrome. Their large genome (> 7000 genes) and multiple pathways encoding the same putative functions make virulence factor identification difficult in these bacteria.

Methods
A novel microarray was designed to the genome of Burkholderia cenocepacia J2315 and transcriptomics used to identify genes that were differentially regulated when the pathogen was grown in a CF sputum-based infection model. Sputum samples from CF individuals infected with the same B. cenocepacia strain as genome isolate were used, hence, other than a dilution into a minimal growth medium (used as the control condition), no further treatment of the sputum was carried out.

Results
A total of 723 coding sequences were significantly altered, with 287 upregulated and 436 downregulated; the microarray-observed expression was validated by quantitative PCR on five selected genes. B. cenocepacia genes with putative functions in antimicrobial resistance, iron uptake, protection against reactive oxygen and nitrogen species, secretion and motility were among the most altered in sputum. Novel upregulated genes included: a transmembrane ferric reductase (BCAL0270) implicated in iron metabolism, a novel protease (BCAL0849) that may play a role in host tissue destruction, an organic hydroperoxide resistance gene (BCAM2753), an oxidoreductase (BCAL1107) and a nitrite/sulfite reductase (BCAM1676) that may play roles in resistance to the host defenses. The assumptions of growth under iron-depletion and oxidative stress formulated from the microarray data were tested and confirmed by independent growth of B. cenocepacia under each respective environmental condition.

Conclusion
Overall, our first full transcriptomic analysis of B. cenocepacia demonstrated the pathogen alters expression of over 10% of the 7176 genes within its genome when it grows in CF sputum. Novel genetic pathways involved in responses to antimicrobial resistance, oxidative stress, and iron metabolism were revealed by the microarray analysis. Virulence factors such as the cable pilus and Cenocepacia Pathogenicity Island were unaltered in expression. However, B. cenocepacia sustained or increased expression of motility-associated genes in sputum, maintaining a potentially invasive phenotype associated with cepacia syndrome.
Acute maternal stress in pregnancy and schizophrenia in offspring: A cohort prospective study
Authors: Malaspina D , Corcoran C , Kleinhaus KR , Perrin MC , Fennig S , Nahon D , Friedlander Y , Harlap S 
Published: September 2008

Abstract
Schizophrenia has been linked with intrauterine exposure to maternal stress due to bereavement, famine and major disasters. Recent evidence suggests that human vulnerability may be greatest in the first trimester of gestation and rodent experiments suggest sex specificity. We aimed to describe the consequence of an acute maternal stress, through a follow-up of offspring whose mothers were pregnant during the Arab-Israeli war of 1967. A priori, we focused on gestational month and offspring's sex.

Method

In a pilot study linking birth records to Israel's Psychiatric Registry, we analyzed data from a cohort of 88,829 born in Jerusalem in 1964–76. Proportional hazards models were used to estimate the relative risk (RR) of schizophrenia, according to month of birth, gender and other variables, while controlling for father's age and other potential confounders. Other causes of hospitalized psychiatric morbidity (grouped together) were analyzed for comparison.

Results

There was a raised incidence of schizophrenia for those who were in the second month of fetal life in June 1967 (RR = 2.3, 1.1–4.7), seen more in females (4.3, 1.7–10.7) than in males (1.2, 0.4–3.8). Results were not explained by secular or seasonal variations, altered birth weight or gestational age. For other conditions, RRs were increased in offspring who had been in the third month of fetal life in June 1967 (2.5, 1.2–5.2), also seen more in females (3.6, 1.3–9.7) than males (1.8, 0.6–5.2).

Conclusion

These findings add to a growing literature, in experimental animals and humans, attributing long term consequences for offspring of maternal gestational stress. They suggest both a sex-specificity and a relatively short gestational time-window for gestational effects on vulnerability to schizophrenia.
Cytoplasmic signaling in the control of mitochondrial uproar?
Authors: Hermann Martin , Kuznetsov Andrey , Maglione Manuel , Smigelskaite Julija , Margreiter Raimund , Troppmair Jakob 
Published: September 2008

Abstract
The concept of a pre-emptive strike as a good means to prevent greater harm may be frequently over-stressed in daily life. However, biological systems in a homeostatic balance are prepared to withstand a certain degree of hostile fire by rather passive means. This also applies to the maintenance of cell survival, where a plethora of protective proteins provide safeguard against erroneous activation of death pathways. Apart from these mechanisms active processes are also essential for the maintenance of cellular homeostasis, commonly referred to as survival signaling. Frequently their targets may be mitochondrial, assuring organelle integrity, which is essential for continued energy production and survival. Transient or permanent failures in these cellular defense strategies result in pathophysiological conditions, which manifest themselves e.g. as cancer or ischemia/reperfusion-associated organ damage.
Lung adenocarcinoma with micropapillary component presenting with metastatic scrotum tumor and cancer-to-cancer metastasis: A case report
Authors: Mori Kiyoshi , Kitazawa Riko , Kondo Takeshi , Kitazawa Sohei 
Published: September 2008

Abstract
A 54-year-old man was admitted to the hospital presenting with a 3-month history of sclerosing dermal lesion in the external genitalia. A scrotal skin biopsy revealed a poorly-differentiated adenocarcinoma, immunohistochemically positive for cytokeratin 7 (CK7) and for thyroid transcription factor 1 (TTF-1), and negative for CK20. One month after admission, he died of respiratory failure. At autopsy, a consolidating lesion with vague margin was noted in the left lung as well as a well-circumscribed nodule in the right lobe of the thyroid. Histopathologically, pulmonary lesion was adenocarcinoma with a micropapillary component. On the other hand, thyroid tumor was diagnosed as a follicular variant of papillary carcinoma with foci of micropapillary adenocarcinoma. Positive immunohistochemistry for surfactant protein on micoropapillary component was useful to confirm that micropapillary component was of lung adenocarcinoma origin.
Type 2 Iodothyronine Deiodinase Is Essential for Thyroid Hormone-Dependent Embryonic Development and Pigmentation in Zebrafish
Authors: Walpita Chaminda N. , Crawford Alexander D. , Janssens Els D. R. , Van der Geyten Serge , Darras Veerle M. 
Published: September 2008

Despite the known importance of thyroid hormones (THs) in vertebrate growth and development, the role of tissue-specific TH activation in early embryogenesis remains unclear. We therefore examined the function of type 2 iodothyronine deiodinase (D2), one of the two tissue-specific enzymes catalyzing the conversion of T4 to T3, in developing zebrafish embryos (Danio rerio). Microinjection of early embryos with antisense oligonucleotides targeting either the D2 translation start site or the splice junction between the first exon and intron induced delays in development and pigmentation, as determined through the measurement of otic vesicle length, head-trunk angle, and pigmentation index at 31 h after fertilization. The antisense-induced delays in developmental progression and pigmentation were reversible through treatment with T3, suggesting that these phenotypic effects may be due to the depletion of intracellular T3 levels. Additional evidence for this hypothesis was provided by quantitative RT-PCR analysis of TH receptor-β expression in D2 knockdown embryos, revealing a significant down-regulation of this T3-induced transcript that could be reversed by T3 treatment. Tyrosinase expression was also down-regulated in D2 knockdown embryos to a greater degree than could be predicted by the observed delay in developmental progression, suggesting that reduced D2 activity and resultant low intracellular T3 availability may directly influence pigmentation in zebrafish. These data indicate that TH activation by D2 is essential for embryonic development and pigmentation in zebrafish.Knockdown of type 2 iodothyronine deiodinase negatively affects development and pigmentation in zebrafish embryos, showing the importance of intracellular thyroid hormone activation in early development.